Denovo cancer is an important complication of organ transplantation.
Knowing about cancer is important for pretransplant counseling and posttransplant screening .
Aim of study: reported denovo malignancy in British solid organ transplant recipients and Compared it with the incidence rates in the general population and compared these incidences following the transplantation of different organs.
Material and methods
The cohort consist of 37617 patients( all patients transplanted in England,Wales and Scotland, who received a first kidney, liver , heart or lung transplant between 1 Jan 1980 and 31 Dec 2007, and who had an NHS number) with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported denovo malignancy or date of death within the study period.
Results
The registery study has shown evidence of different patterns of cancer occurrence in recipients of different organ type. The overall incidence of cancer ( excluding NMSC) in recipients of a heart, kidney or liver is over twice that of general population and over three times higher in recipients of lung or combined lung and heart transplants.
NMSC is the most common malignancy with a standardized incidence ratio of over than 16 for kidney and cardiothoracic transplant patients, which is three higher than that for liver transplants.
Level of evidence II
What are the drawbacks of registery data
Incomplete data registration, missing outcomes and loss of follow-up data
1. Please summarize this article Introduction It is known that cancer risk increased after organ transplantation. Knowing the exact incidence of individual organ and comparison of different organs risk will influence counselling of patient pre transplantation and monitoring and screening post transplantation. This is the first national registry data that compared denovo cancer incidence in organ transplantation with that of general population. Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), has been linked to information on cancer registrations following solid organ transplantation recorded by the eight cancer registries in England and the separate registries for Wales and Scotland, using the NHS number. This number was not available for 17% of all transplant recipients since 1980, mainly those in the 1980s. Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population. Result
Of the 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung). The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years). A total of 5706 patients (15%) developed a cancer in this period. Ten years after transplan[1]tation, recipients have an overall incidence rate of 90 per Figure 1: Overall cumulative incidence of any de novo cancer (excluding nonmelanoma skin cancer) in the transplanted and general populations. thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period. This overall relative risk is more or less constant from two years after transplantation. NMSC is much more common, and the corresponding standardized incidence was 14.4 (95% confidence interval: 13.8–15.0), meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these pa[1]tients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. 2. What is the level of evidence provided by this article? 11 3. What are the drawbacks when we use the registry data? Uncertainty of accuracy. Loss of a lot of data Retrospective nature. Rely on how accuracy is the data and its collection.
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number. Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients. The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR) (9). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.All calculations were carried out using Statistical Analysis Software (SAS Institute, Cary). Computation of the incidence functions and the person years at risk was based on SAS macros
Results
Of the 37617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung). The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).A total of 5706 patients (15%) developed a cancer in this period. The overall incidence of cancer (excludingNMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
Conclusion-
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. These results have implications for a national screening program.
What is the level of evidence provided by this article?
Level 2
What are the drawbacks when we use the registry data?
A weakness of the study is the lack of complete data on immunosuppression
· This observational longitudinal cohort study compared the incidence of de novo malignancy in SOT recipients with general population using the Standardized Incidence Ratio (SIR). · It included all UK transplant patients from the (NHSBT data) from 1980 to 2007 · However, it excluded patients with diagnosis of cancer within one month post-transplant and PTLD. · Results: · The median follow up period of this study was 16 years(range: 8–26 years) · The 10-year incidence of de novo malignancy in post-transplant patients was double that of general population. Also, non-melanoma skin cancer being the commonest(13 times greater than the general population). · Other common cancers were cancer of the lip, Kaposi sarcoma, PTLD, anal cancer and kidney cancer. Level of evidence: · Level 2 What are the drawbacks when we use the registry data? · Limited amount of data from the data registry · Selection bias. · Lack of follow-up
The elevated risk of developing de novo malignancies is documented complication of solid organ transplantation as well as immunosuppression. Proper identification of risk factors presents to better rational approach to screening and surveillance later on. However this is the first unique work performed concerned by the study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
The study cohort involves all patients transplanted in England, Wales and Scotland, who received kidney, liver, heart, lung transplant,combined pancreas and kidney transplant or combined heart and double lung transplant between 1 January 1980 and 31 December 2007.
Those who underwent pancreas transplant alone were excluded, together with all other multi-organ transplant recipients. Also it was important to exclude cancers that may have been prevalent at the time of transplantation, so all patients with cancer diagnosis within one month of transplant were excluded except for the 620 patients diagnosed with post-transplant lymphoproliferative disease (PTLD).
The cohort consists of 37 617 transplanted patients with documented age and gender at transplantation. Study period covered the followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death.
Statistical methods
The Standardized Incidence Ratio (SIR) is the main point used to compare the cancer incidence in the transplant population to the general UK population. It relies on the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.
Data such as the expected number of incident cases was obtained by calculating the person years at risk of malignancy in the transplant population in five year age groups for each gender in each year between 1980 and 2007 was applied in the study.
Confidence intervals for these estimates and p-values for testing the hypothesis that the SIR is 1.0 were evaluated. It is worthy to mention that this analysis extended to 15 years following transplantation, and was carried out for each organ and all the different cancers.
For each organ type, the estimated cancer incidence on recipient age group and gender, primary disease, smoking history, obesity, dialytic status at the time of registration and transplant year [1980–1984, 1985–1989,1990–1994, 1995–1999, 2000–2004, 2005–2007] was modeled. One drawback of the study is the availability of smoking history which was absent in 70% in kidney recipients as well as obesity and immunosuppression.
The calculations were performed by using Statistical Analysis Software (SAS).
Results
A total of 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5%a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC (C44), and of these 426 were subsequently registered as having developed a different de novo cancer. The other 2856 patients were registered with a de novo cancer other than a non-melanoma skin cancer.
Ten years post transplantation, recipients have an incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
This estimated relative risk is nearly constant from two years post transplantation. NMSC is by far more prevalent with SIR was 14.4 (95% confidence interval: 13.8–15.0), which is best explained by the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The standardized incidence ratios are particularly high for non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients. The incidence of non-melanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients.
Concerning Lymphoma rates which are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was particularly alcoholic liver disease.
The incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. Interestingly, the SIR following lung transplantation increases dramatically at first and then declines over time.
The pattern is similar for liver recipients, although the SIR is generally lower.
Notably the SIR for non-Hodgkin’s lymphoma increases for all organs to a maximum at one year after transplantation and then declines. Post renal transplantation, the SIR increases for some cancers as NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach while decreases for others as Kaposi sarcoma, leukaemia.
The SIRs for liver and ovarian cancer increase in the years immediately post transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Concerning post liver transplantation, the SIR for several cancers as cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas peaks within 2 years of transplantation, and then declines steadily.
For post heart transplant recipients, the SIR for bladder, lung and oral cancer and Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
The pattern is similar following lung transplantation, except there is lack of evidence for the increase over time in the SIR for leukaemia and lung cancer.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
Fortunately, the incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Body mass index, and dialytic status at time of listing for transplantation did not significantly affect the hazard of cancer evident by these p values (p = 0.75 and 0.54, respectively).
For liver recipients, the recipient age group and primary disease affected the risk of skin cancer (p < 0.001 and 0.01, respectively) and colorectal cancer (p = 0.06 and 0.002, respectively).
Also it was shown that the risk of PTLD only depended on recipient gender (p = 0.02), and the risk of lung cancer depended only on recipient age group (p = 0.02). For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients (p = 0.004).
Regarding the impact of initial immunosuppression from the presented data only in renal transplant recipients the incidence of NMSC was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin.
Discussion
The overall incidence of cancer (except for NMSC), in recipients of a heart, kidney or liver, is exceeding double that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSC is still the most encountered malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
Liver recipients astonishingly appear to be relatively protected against cancer of the lip and anal canal, diseases which, like NMSC, have an underlying viral association and the lower rise in incidence for which may reflect lower doses of maintenance immunosuppression especially avoidance of azathioprine as well as the absence of biological induction agents in liver transplant immunosuppressive protocols.
Cigarette smoking for instance may be a contributing factor for the need of lung transplantation (emphysema) or heart transplantation (ischaemic cardiomyopathy).
Primary sclerosing cholangitis may require liver transplantation, but is also associated with colitis which might explain the increase in incidence of cancer of the colon and rectum; like alcohol (and the exposure to cigarette smoking which accompanies it) may account for the higher risk of oral cancer in liver recipients. Analgesic nephropathy or aristolochia use may necessitate renal transplantation, are also themselves risk factors for development of transitional cell carcinoma of the native urothelium.
The study again highlights the very high incidence of post-transplant lymphoma and Kaposi’s sarcoma. The incidence of post-transplant lymphoma in renal transplant recipients has increased ninefold since 1980–1984, an observation linked to the more aggressive immunosuppressive protocols being used.
It was also found that the incidence of breast cancer was twice that of the normal population. Other tumours as cervical carcinoma was known to have higher incidence as it is a consequence of papilloma virus infection but this has been overcome by the active cervical screening program in which the disease is being detected and treated before it even becomes invasive.
The importance highlighted on increased cancer risk is that clinicians during regular follow up are now aware of as well as this reflects the role of intense immunosuppression rather than being attributed to any particular drugs, since patients get immunosuppressed as a complication of human immunodeficiency virus infection have a similar pattern of increased cancer incidence.
The significance of studies such as ours is to identify patient groups, cancer types, which should form part of a cancer surveillance program, as well as to provide data for proper counselling pretransplant patients on the risk of malignancy.
The suggested recommendations for the time following transplantation for all transplant recipients is to screen for NMSC, including lip and anal cancer on regular basis being combined with lifestyle changes to reduce sun exposure. The need for any additional breast or cervical cancer screening wasn’t proved to be of value in such population.
Regarding liver transplant recipient it is advised that alcoholics should have regular surveillance of the aerodigestive tract. Also it is necessary for recipients suffering from primary sclerosing cholangitis disease to undergo regular colonoscopy.
The presence of recurrent graft cirrhosis mandates to regular ultrasound surveillance for hepatocellular carcinoma.
Other recommendations advocate regular ultrasound scans of renal transplant recipients to their transplant and native kidneys for evidence of tumor, particularly those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is further indicated.
Level Of evidence: II
The drawbacks when we use the registry data are mainly lack of complete information concerning obesity, smoking, immunosuppression protocols, and different induction protocols with different transplanted organs, unreported malignancies are also missed in both general and transplant population as well as variations among different countries.
Introduction de novo cancer development is an established complication of organ transplantation.
Understanding the increased risk of cancers and the most common cancer types will help to clearly inform the patient before transplantation and allow a rational approach to screening and surveillance in the postoperative period.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
other studies investigated cancer incidence in recipients of a kidney, liver or cardiothoracic organ, with a focus on a single transplant type, a specific form of malignancy, experience at a single center, or a limited duration of follow-up.
Some other registries rely on voluntary reporting, leading to the underestimation of cancer incidence following transplantation. Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), was linked to information on cancer registrations following SOT recorded by 8 cancer registries in England and in Wales and Scotland.
It included all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
The registry included 37 617 transplanted patients, they were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Cancer Registries code any new malignancy on the basis of available histology and other relevant information.
all patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD).
Incidence of malignancy were compared transplant recipients and general population, matched for age, sex and time after TX. Results and discussion:
-Numbers of diagnosed number in the period 1980–1984 was low than because of incomplete recording.
-The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years)
– 5706 patients (15%) developed a cancer in this period.
– In 3276 patients, the first cancer registered following transplantation was a NMSC, and of these 426 were subsequently registered as having developed a different de novo cancer. Thus 2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer.
-Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
– the risk of NMSC in a transplant recipient is over 14 times that of the general population.
-The incidence rate of cancer in the transplanted population is twice the general population.
-nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma are the most common cancers in transplant population.
-The incidence of nonmelanoma skin cancer is much less in liver recipients -Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
-The incidence of oral cancer in liver recipients is high, more in patients with alcoholic liver disease.
-the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation.
-the SIR for non-Hodgkin’s lymphoma for all organs increases to a maximum at one year after transplantation and then declines.
-KTRs have higher rates of some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for others (Kaposi sarcoma, leukemia). Factors affecting time to cancer diagnosis
many factors affected the incidence of post transplantation malignancy
-rates were greater in males than females,
-The incidence increased age.
-The risks of developing PTLD and kidney cancer have increased over the study period.
-Body mass index and whether or not a patient was on dialysis at time of listing for transplantation where available, did not significantly affect the hazard of cancer.
– incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data.
– NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
However, this risk may be underestimate since reporting of skin cancers may not be complete because some lesions will be removed or ablated without histological confirmation and some of the cancer registries did not collect data on basal cell carcinomas.
– incidence rates of many cancers in UK are similar to those reported by Canada, Australia and Sweden, but there are also some important differences.
– renal cell carcinoma showed higher rates in KTRs over the study period, the reason is not clear, may be due to increasing age of the recipient in whom renal malignancy is more common and in part the occurrence of cancer in acquired cystic disease of the native kidneys.
Also the registries do not distinguish between cancers arising in the native kidneys or in the transplant.
– weakness of the study is the lack of complete data on immunosuppression protocols and differences in induction and immunosuppression protocols in centers. level of evidence II.
drawbacks when we use the registry data?
Variability in data collection.
Poor quality of data
Absence of follow up
selection bias
no control group
Introduction
It is a well-known side effect that following organ donation and the ensuing immune suppression, there is an elevated chance of developing de novo cancer. De novo malignancy in British solid organ transplant patients was the subject of this country-wide investigation. It contrasts the incidence rates of de novo cancer in patients who have received organ transplants with those in the general population.
Methods
All patients with an NHS number who underwent their first kidney, lung, liver, heart, or lung transplant in England, Wales, or Scotland between January 1980 and December 31, 2007, are included in the study. The cohort included 37 617 transplant recipients whose age and gender were known at the time of the procedure. The standardized incidence ratio (SIR) was used to compare the incidence of de novo malignancies to the overall UK population.
Results
Of the 37 617 patients who underwent transplantation, 67% received a kidney, 18% a liver, 10% a heart, and 5% a lung. 5706 individuals (15%) who underwent transplants later developed cancer. Non-melanoma skin cancer (NMSC) was the most prevalent type of cancer.
Overall, transplant recipients had a cancer incidence rate that was just over twice as high as the general population. The frequency of non-Hodgkin’s lymphoma grew to a maximum after 1 year following transplantation for all organ transplants, then it began to fall.
Following kidney transplantation, the SIR changed for some cancers, including Kaposi sarcoma and leukemia, and decreased for others, including NMSC, anal, cervical, Hodgkin’s lymphoma, kidney, oesophagus, and stomach.
The SIR for several malignancies (cervical, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreatic) after liver transplantation peaked within 2 years following transplantation, then began to fall.
The SIR for bladder, lung, oral cancer, and Hodgkin’s lymphoma rose with time in patients who had heart and lung transplants.
Discussion
The total incidence of cancer (excluding NMSC) was more than twice the population average among transplant recipients who had received a heart, kidney, liver, and more than three times the average in individuals who had received a lung transplant. The most frequent kind of cancer seen in recipients of kidney and cardiothoracic transplants was NMSC. It is crucial to remember that not all cancer cases were reported to the appropriate authorities by the general public. Additionally, certain patients might have been exposed to carcinogens like cigarette smoke. The absence of comprehensive information regarding immune suppression was one of the study’s flaws.
In conclusion, the study proved that frequent NMSC screenings are necessary for all transplant patients. It was recognized that extra screening for cervical and breast cancer was unnecessary. To learn more about the advantages of early screening in immune-suppressed post-transplant patients, more research is needed.
Introduction
It is a known complication that there is an increased risk of developing de novo cancer after organ transplantation and the associated immune suppression. This was a national study of de novo malignancy in British solid organ transplant recipients. It compares the incidence rates of de novo malignancy in the general population with patients who have undergone organ transplantation.
Methods
The study consists of all patients transplanted in England, Wales and Scotland who received a first kidney, lung, liver, heart and/or lung transplant between January 1980 and 31 December 2007, who had an NHS number. The cohort consisted of 37 617 transplanted patients with known age and gender at transplantation. The incidence of de novo cancers was compared to the general UK population using the standardized incidence ratio (SIR).
Results
Out of the 37 617 transplanted patients, 67% received a kidney, 18% received a liver, 10% received a heart and 5% received a lung. 5706 (15%) patients developed cancer after transplantation. The most common cancer was a non-melanoma skin cancer (NMSC).
The overall incidence rate of cancer in transplanted patients was just over twice that of the general population. For all organ transplants, the incidence of non-Hodgkin’s lymphoma increased to a maximum after 1 year after transplantation, then declined.
After kidney transplantation, the SIR increased for some cancers, such as NMSC, anal, cervical, Hodgkin’s lymphoma, kidney, oesophagus and stomach, and it decreased for some cancers (such as Kaposi sarcoma, leukemia).
After liver transplantation, the SIR for some cancers (cervical, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas), peaked within 2 years of transplantation, then declined.
In heart and lung transplant recipients, the SIR for bladder, lung, oral cancer and Hodgkin’s lymphoma increased over time.
Discussion
The overall incidence of cancer (excluding NMSC) in recipients who had received a heart, kidney or liver transplant was over twice that of the general population, and over thrice in patients who received lung transplants. NMSC was the most common malignancy noted in kidney and cardiothoracic transplant patients. It is important to note that some cancers may have been under reported in the general population. Some patients may also have been exposed to carcinogens, such as cigarette smoke. One of the weaknesses of the study was the lack of complete data on the immune suppression.
In summary, the study confirmed that all transplant recipients should be screened regularly for NMSC. It was noted that there was no need to screen additionally for breast and cervical cancers. Further studies are required to provide additional information on the benefits of early screening in post-transplant patients receiving immune suppression.
Level of Evidence: II
Drawbacks of Registries:
Registries are subject to confounders
There is no control of the data collection
It is difficult to compare the obtained results to those of prospective comparative studies
Introduction This study investigates the increased risk of de novo cancer in organ transplant recipients in the UK between 1980 and 2007.
In this study researchers compared, cancer incidence in transplant patients with the general population. this was aimed to better understand risks and inform the same to patients before transplantation.
Methods The study considered factors such as age, gender, primary disease, smoking history, obesity, dialysis, and transplant year while doing analysis. A competing risks Cox regression analysis was used to model cancer incidence dependence on these factors. The analysis also compared immunosuppression usage in kidney recipients.
This study analyzed 37,617 organ transplant recipients in the UK between 1980 and 2007. Of these, 15% developed cancer during the follow-up period, with 3276 patients having their first post-transplant cancer as nonmelanoma skin cancer (NMSC).
The overall incidence rate of de novo cancer (excluding NMSC) in transplant recipients was more than double the general population’s rate. The risk of NMSC in transplant recipients was over 14 times higher than the general population.
Standardized incidence ratios (SIRs) were particularly high for NMSC, cancer of the lip, and Kaposi sarcoma. SIRs were greatest for lung transplant recipients and varied for different transplant types.
Discussion
Current study under discussion is probably the first detailed registry analysis of cancer occurrence in British organ transplant recipients, revealing distinct patterns of cancer occurrence among recipients of different organ types. The overall incidence of cancer (excluding non-melanoma skin cancer or NMSC) in heart, kidney, and liver recipients is more than twice that of the general population. The incidence is more than three times higher in lung or combined heart and lung transplant recipients.
NMSC came out to be the most common malignancy, with a significantly higher incidence among kidney and cardiothoracic transplant recipients compared to liver recipients.
It was also observed that transplant recipients experience a very high incidence of post-transplant lymphoma and Kaposi’s sarcoma, most probably due to aggressive immunosuppressive protocols and the development of antimicrobial drugs.
Weakness:
Lack of complete data on immunosuppression.
The findings of this study can help inform cancer surveillance programs and pre-transplant patient counseling on malignancy risks. All transplant recipients should be screened regularly for NMSC, lip, and anal cancer and encouraged to adopt lifestyle changes to reduce sun exposure.
Renal transplant recipients, particularly those with specific risk factors, may also benefit from regular ultrasound scans of their transplant and native kidneys, as well as cystoscopic examination of the urothelium.
What are the drawbacks when we use the registry data
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs. Understanding the increased risk and defining those cancers that are increased in these patients will inform the patient prior to transplantation and allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods:
The study cohort consists of all patients transplanted in England, Wales and Scotland who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007. The cohort consists of 37 617 transplanted patients with known age and gender at transplantation, followed up from the date of first reported de novo malignancy to the earliest date of death. Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). Cox regression models adjusted for recipient age group, gender, primary disease, smoking history, obesity, dialysis, and immunosuppression were used to test the hypothesis that the SIR is 1.0.
Results :
Of 37617 transplanted patients 67%receiving a kidney or simultaneous kidney ,pancreas , 18% a liver, 10% a heart and 5% a lung. A total of 5706 patients developed a cancer in this period, with the first cancer registered being a NMSC (C44). Ten years after transplantation, recipients have an overall incidence rate of 90%, more than double the 10-year incidence rate for the population of England. The overall incidence rate of cancer in the transplanted population is over twice that of the general population, with high incidence ratios for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma. Lung transplant recipients have the greatest SIR, while lymphoma rates are similar, except for non-Hodgkin’s lymphoma in cardiothoracic patients. Discussion:
The incidence of cancer in British transplant recipients is over twice that of the general population, with NMSC being the most common malignancy. Heart transplant recipients receive higher levels of CNI triple therapy, while liver recipients receive a lower immunosuppressive burden. All transplant recipients should be screened regularly for NMSC, combined with lifestyle changes to reduce sun exposure, and there is no need for additional breast or cervical cancer screening. . What is the level of evidence provided by this article?
level 2 retrospective cohort
What are the drawbacks when we use the registry data? Lack of data verification
Data are incomplete with variable quality
There is selection bias
Lack of control group
There is underestimation of cases plus loss of follow up with length of time
Q1- Please summarise this article
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. In this study on cancer incidence in solid organ transplant recipients in Britain, the author describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs.
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of non melanoma skin cancer being 13 times greater. Non melanoma skin cancer, cancer of the lip, post- transplant lympho -proliferative disease and anal cancer have the largest standardized incidence ratios.
the incidence of different types of malignancy differs according to the organ transplanted.
Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient ,as well as for different malignancies.
Introduction
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated with immunosuppression.
Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
The overall SIR is greatest for lung transplant recipients.
For all organs, the SIR for non-Hodgkin’s lymphoma in creases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs.
Following kidney transplantation, the SIR increases for some cancers
(NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population. Impact of initial immunosuppression:
the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin.
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice
that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSCis the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is threetimes higher than that for liver recipients.
Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens, Cigarette smoking, Primary sclerosing cholangitis, alcohol, Analgesic nephropathy or aristolochia use may necessitate renal transplantation, while being associated with transitional cell carcinoma of the native urothelium.
this study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC.
The incidence of posttransplant lymphoma in kidney recipients has increased nine fold since 1980–1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
The other cancer whose incidence is clearly increasing in renal transplant recipients over the study period is renal cell carcinoma.
One cancer whose incidence is not increased in this study , is breast cancer.
Another tumor whose incidence might be expected to be higher is cervical carcinoma, since it is known to be a consequence of papilloma virus infection .
the increased risk of cancer in transplant recipients is a reflection of being immunosuppressed rather than being attributable to any particular drugs, since patients immunesuppressed
as a complication of human immunodeficiency virus infection have a similar pattern of increased cancer incidence.
This Studies identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy.
Following transplantation,
This study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure (26). But , there is no need for any additional breast or cervical cancer screening.
Q2- What is the level of evidence provided by this article? Level 2
Q3- What are the drawbacks when we use the registry data?
Drawback of registery studies
1- Retrospective study .
2- Heterogeneity of collected data .
3- Non conclusive and usually needs further well designed study to prove the result .
4- No control group.
5- No follow up result
Malignancies are more common in solid organ transplant recipients than general population. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period. Aim of the study was to compare incidence of de novo malignancy in solid organ transplant with general population and compere these incidences with different organs in the British population.
A cross sectional observational study with a cohort of all solid organ recipients between 1980 and 2007 (27 years, 37617 patients) was selected and cross referenced with cancer registries in in England, Wales and Scotland. Those patients diagnosed with malignancy in first month post-transplant were excluded. This incidence was compared to general population using standardized incidence ratio (SIR).
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL). Different factors appeared to affect the incidence of various cancers among these transplant recipients. In general, for all transplant recipients, the risk of cancer was higher in males than females, and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
Regular ultrasounds, surveillance of aerodigestive tract, and colonoscopy can be done for transplant recipients, to detect changes in favor of liver, lung, colon, kidney, or anal cancer. How helpful this is toward long term outcome is yet to be seen.
The limitations of this study mainly stem from the design and data collection method. The data was lacking key confounders such as history of smoking, history of dialysis before renal transplantation and incomplete data with regards to post transplant immunosuppression.
What is the level of evidence provided by this article?
Level II as it is a retrospective cohort study.
What are the drawbacks when we use the registry data?
1. Data are pre-collected by others than researchers. Necessary information may be unavailable or misclassified. Often hard to know exactly how data are generated. Limited to use variables in register. Variation in coding between persons and institutions
2. Lack of confounder information
3. Missing data difficult to handle. Difficult to know what missing data means and can lead to under coverage.
4. Low or unknown data quality
5. Unimportant differences become statistical significant
Introduction:
This study describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs. It is the first reported national study of de novo malignancy in British solid organ transplant recipients
Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), has been linked to information on cancer registrations following solid organ transplantation recorded by cancer registries in England, Wales and Scotland between 1 January 1980 and 31 December 2007.
All patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD). The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR)
Results
25104(67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years
A total of 5706 patients (15%) developed a cancer in this period.
2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer.
The incidence for all de novo cancers, excluding nonmelanoma skin cancer have an over all incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England.
NMSC is much more common with a risk of over 14 times that of the general population.
There is evidence of different pattern of cancer occurrence in recipients of different organ types.
What is the level of evidence provided by this article?
Level II
What are the drawbacks when we use the registry data?
Main drawback for using registry date is the variability in data collection from multiple sources and incomplete date or the risk of using a date that was inaccurately labeled with ICD codes in the registry. Selective bias is one of the important limitation that can occur with this kind of date.
: One of the side effects of immunosuppression treatment is increasing the rate of de novo cancer. In this study, using the UK Transplant Registry, the incidence rate of de novo cancer in transplanted patients was compared with the general population.
sixty-seven percent of the 37617 transplanted patients received a kidney with a median follow-up of 16 years. Fifty percent (5706) of the patients were affected by cancer. Most of them (3276 patients) had nonmelanoma skin cancer. The incidence rate was 90 per 1000 which was more than double of the ten-year incidence in the general population.
Q2: This is a longitudinal cohort study (Level II).
Q3: Limitations include:
no active follow-up
Variable data collection
selective bias
incomplete data
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit
Introduction
de novo cancer development is an established complication of organ transplantation and immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will inform the patient prior to transplan- tation and allow a rational approach to screening and surveillance in the postoperative period.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales.
Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period.
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Inclusions criteria:
Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients.
patients whose first reported cancer following the date of transplantation is an in situ tumor ,a benign tumor or a tumor of uncertain or unstated behavior ,the date and code of any subsequent malignant tumor was used.
The time to first occurrence of a nonmelanoma skin cancer (NMSC) was obtained for all individuals whose first registration was this cancer. Exclusion criteria:
The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).
all patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD), defined as the occurrence of Hodgkin’s or non-Hodgkin’s lymphoma. Results:
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period.
the first cancer registered in 3276 patients following transplantation was a NMSC .
2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer.
Ten years after transplantation, recipients have an overall incidence rate of 90 per
thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
NMSC is much more common, and the corresponding standardized incidence was 14.4 meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients.
The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients.
Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease.
the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower.
the SIR for non-Hodgkin’s lymphoma for all organs increases to a maximum at one year after transplantation and then declines.
The patterns in the incidence rates of many other malignancies vary between organs.
Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily.
In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer.
the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Factors affecting time to cancer diagnosis
Age
Gender
Body mass index
whether or not a patient was on dialysis at time of listing for transplantation
For recipients of a liver, recipient age group and primary disease affected the risk of skin cancer and colorectal cancer .
The risk of PTLD only depended on recipient gender ,and the risk of lung cancer depended only on recipient age group .
For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients.
Impact of initial immunosuppression
the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data for reliable estimates.
What is the level of evidence provided by this article?
Level 2 Drawback:
No active follow up
Retrospect data
Selective bias
Variable data collection.
Impact of organ transplantation and the ensuing immunosuppression is an increased risk of cancer.
It’s necessary not only to educate the patient prior to transplantation but also to provide a practical method for screening and surveillance throughout the postoperative period
METHOD:
The incidence of de novo malignancies in allograft recipients has been described in this study on the cancer incidence in solid organ transplant recipients in Britain, and occurrences following the transplantation of various organs have been compared.
Using standardized incidence ratios that were matched for GENDER, AGE and TIME PERIOD, incidence rates in the transplanted group were then compared with those in the general population.
RESULT:
Result concludes that in transplant patients, de novo cancer occurs twice as frequently (10 times more frequently) as in the general population, with nonmelanoma skin cancer occurring 13 times more frequently.
The biggest standardized incidence ratios are for nonmelanoma skin cancer, lip cancer, posttransplant lymphoproliferative illness, and anal cancer, however, the incidence of various malignancies varies depending on the organ that was transplanted.
Varied types of transplant recipients and various malignancies show different trends in standardized incidence ratios during the years following the transplant.
Conclusion:
A heart, kidney, or liver transplant recipient’s overall risk of developing cancer is more than twice that of the general population, and a lung transplant recipient’s risk of developing cancer is more than three times greater.
The most prevalent kind of cancer among transplant recipients is Non Melanoma Skin Cancer
Frequent NMSC screening, lifestyle adjustments to decrease sun exposure especially use of sun block and regular alcohol surveillance in patients having liver transplants all contribute significantly to the goal of early cancer detection.
The level of evidence provided by this article:
Level II (Retrospective cohort study)
The drawbacks when we use the registry data:
observational study of level 1 evidence
Data on immunosuppression is not available
Possible influence of confounders
Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
To evaluate the incidence of de-novo cancer in the general population and solid organ transplant recipients and to compare the incidence of de-novo cancers among different organ transplantation.
Methods
This is a retrospective cohort study for all solid organ transplant recipients obtain data from cancer registries in England, Wales and Scotland. In this study standardized Incidence Ratios matched for age, gender and time period were used to compare de-novo malignancy in solid organ transplant recipients with general population.
Results
Among 37617 transplanted patients 67% kidney, 18% liver, 10% heart, and 5% of lung transplant. Median follow up was 16 years. 15% patients develop cancer in this time frame. 3276 patients got first time cancer and registered. The most common cancer is non-melanoma skin cancer and its incidence is higher than that of general population.
Conclusion
The study identify patient groups and cancer types, aids in surveillance programs, and provides information on warning transplant candidates about the possibility of cancer
What is the level of evidence provided by this article?
Level IV evidence
What are the drawbacks when we use the registry data?
Data from multiple sources and countries There can be selection bias Incomplete data Incomplete or loss to follow up Potential outcomes maybe lacking
Summary of the article:
study type – Retrospective analysis (cohort study) of UK cancer registry audit
published in Am J Transplant 2010
Introduction
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
Understanding the increased risk and identifying cancers increased in transplant recipients will help in pretransplant counselling of patients and as well as to develop rational approach for cancer screening and surveillance in the post- transplant patients.
Most of the available studies on the incidence of de novo cancer following transplantation are usually limited because they are generally single-center studies, in a specific form of malignancy (kidney / liver / thoracic), or of limited duration follow-up.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
Data of transplant recipients in the UK held by NHS-Blood & Transplant registry was linked to information on cancer registrations by the 10 cancer registries (8 in England, 1 in Wales and 1 in Scotland) using the NHS number.
Study period – Jan 1980 – Dec 2007
Inclusion criteria:
recipients of first kidney, liver, heart, or lung transplant between 01 Jan 1980 and 31 Dec 2007
combined heart-lung and double lung transplant recipients were classified as “lung transplant recipients”
pre-existing malignancy – cancer diagnosis within one month after transplantation (except PTLD)
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR).
Patterns in cancer incidence over the time period following transplantation have been evaluated by further stratifying the SIRs by year since transplantation.
This analysis extended to 15 years following transplantation, and was carried out for each organ and all the different cancers.
Results and discussion
37,617 solid organ transplants recipients were included in the study with a median follow-up period of 16 (8–26 years).
of the 3276 patients who developed Non-Melanoma Skin Cancer (NMSC) within a year, 426 reported a second de novo malignancy later on
2856 developed other forms of cancer apart from NMSC
Incidence rate of cancer in the transplant population is over twice that of the general population – the SIR was high for NMSC, Cancer of the lip and Kaposi sarcoma.
Age & Gender predisposition – SIRs for each cancer decrease with increasing age, and rates are higher for males than females. Other than NMSC and PTLD, the incidence of cancer in recipients over 50 is not significantly higher than in the general population.
Most common malignancy is NMSC (SIR >16) for kidney and cardiothoracic transplant recipients, which is three times higher than that for the liver recipient.
This study shows high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers (except NMSC).
Trends of cancer development with time
When compared to the general population, the incidence rate quickly rises to twice that of the general population following kidney or heart transplantation.
The SIR after lung transplantation rises dramatically initially, then falls over time. For liver recipients, the pattern is similar, though the SIR is generally lower.
The SIR for non- Hodgkin’s lymphoma increases to maximum at one year after transplantation and then declines across all organs, but patterns in the incidence rates of many other malignancies vary by organ.
kidney transplantrecipients – SIR increases for NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus, and stomach) where as it remains same for leukemia.
SIRs for liver and ovarian cancer rise immediately after transplantation and then fall, whereas SIRs for breast, uterine, prostate and pancreas cancer remain constant.
Liver transplant recipients – the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreas) peaks within two years, then steadily declines.
Heart transplant recipients – the SIR for bladder, lung, and oral cancer, as well as Hodgkin’s lymphoma, increases over time in, whereas those for the majority of other cancers remain stable or decrease.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukaemia and lung cancer.
Limitations:
The lack of complete data on immunosuppression.
Actual incidence of cancers likely to be under-estimated due to various reasons — study censored recipients at the first occurrence of any cancer mostly based on self reporting premalignant lesions are sometimes ablated / cauterized but may not be reported development of a second cancer would not be recorded.
Renal cancer: registries do not distinguish between cancers arising in the native kidneys or in the transplant allograft kidney (aging donor population may have an unrecognized renal cancer at the time of transplant).
Conclusions:
This study identifies patient groups and cancer types for cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy.
All transplant recipients should be screened regularly for NMSC, lip and anal cancer, and it should be combined with lifestyle changes to reduce sun exposure
No need for any additional breast or cervical cancer screening.
Patients undergoing liver transplant for alcohol should have regular surveillance of the aerodigestive tract
2.What is the level of evidence provided by this article?
Level 2(Retrospective Cohort study)
3.What are the drawbacks when we use the registry data?
Retrospective Data analysis
Assessment / treatment criteria may not be uniform – potential selection bias
Patients seen in diverse centers / countries — variability in data collection and lack of verification
Data collected anonymously – chances of duplicity of records on same patient
Lack of active follow-up – may not have complete data, some events might be underestimated
No control population unlike in RCT
There is no specific tool for assessing the quality of a registry-based study
potential for industry influence on analytical method
the intended design may not lead to an outcome of a certain quality
Please summaries this article
Publised in American Journal of Transplantation 2010; 10: 1
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
So, this study examined and compared the rates after different organ transplants. This study included data from 10 cancer registries (8 from England, 1 from Wales, and 1 from Scotland) from 1980 to 2007. 37,617 first-time kidney, liver, heart, or lung transplant recipients were included.
All patients transplanted in England, Wales, and Scotland between 1 January 1980 and 31 December 2007 who got their first kidney, liver, heart, or lung transplant and had an NHS number are included in the study cohort. Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). Ten years after transplantation, recipients have an overall incidence rate of 90 per
Results
The study found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to the UK.
Time trends following transplantation.
When compared to the general population, the incidence rate quickly rises to twice that of the general population following kidney or heart transplantation.
The SIR after lung transplantation rises dramatically at first, then falls over time. For liver recipients, the pattern is similar, though the SIR is generally lower.
The SIR for non- Hodgkin’s lymphoma increases to a maximum one year after transplantation and then declines across all organs, but patterns in the incidence rates of many other malignancies vary by organ.
The SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus, and stomach) and decreases for others after kidney transplantation (Kaposi sarcoma, leukaemia).
SIRs for liver and ovarian cancer rise immediately after transplantation and then fall, whereas SIRs for breast, pancreas, and uterine cancer remain constant.
The SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreas) peaks within two years of liver transplantation and then steadily declines.
The SIR for bladder, lung, and oral cancer, as well as Hodgkin’s lymphoma, increases over time in heart transplant recipients, whereas those for the majority of other cancers remain stable or decrease.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukaemia and lung cancer.
The SIRs for each cancer generally decrease with increasing age, and many of the rates are higher in men than in women.
Other than NMSC and PTLD, the incidence of cancer in recipients over 50 is not significantly higher than in the general population.
Limitations
The lack of complete data on immunosuppression.
The cancer incidence rates are likely to be under-estimated because the study censored recipients at the first occurrence of any cancer, so if a recipient developed a second cancer, it would not be recorded.
Renal cancer: registries do not distinguish between cancers arising in the native kidneys or in the transplant, and it is possible that the increase in incidence also reflects the aging donor population who may have an unrecognized renal cancer at the time of transplant.
Conclusion
Following transplantation, this study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure.
What is the level of evidence provided by this article? Level 2
What are the drawbacks when we use the registry data?
Variable data quality
Lack of active follow-up
There is no specific tool for assessing the quality of a registry-based study.
One of the known complications of solid organ transplantation is the development of cancer due to the immunosuppressive effects of medication used during and after the surgery. Most of the available studies on the incidence of de novo cancer following transplantation are usually limited because they are generally single-centre studies, specific to a form of malignancy, and of a limited follow-up duration.
The British solid organ transplant recipients make comparisons with incidence rates in the general population and compare these incidences following the transplantation of different organs.
Materials and Methods
Data of transplant recipients in the UK held by NHSBT Involving eight cancer registries centres were used in the study
Inclusion criteria:
those who received a first kidney, liver, heart, or lung transplant between 1 January 1980 and 31 December 2007
those that have NHS number
those who received a combined heart and double lung transplant ( were classed as lung transplant recipients
those who received a combined pancreas and kidney transplant were taken to be kidney recipients
Exclusion criteria
recipients with pancreas transplants alone
those with multi-organ transplant
those with cancer diagnosis within one month after transplantation except those with PTLD
Results and discussion
37,617 individuals received different forms of transplantation within the studied years
67% received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart, and 5% a lung (or heart/lung).
the median follow-up was 16 years with an interquartile range: of 8–26 years.
a total of 5706 patients (15%) developed cancer in this period and 3276 developed NSMC within a year
a total of 2856 developed other forms of cancer asides from NMSC
the overall incidence rate of cancer in the transplanted population is just over twice that of the general population.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
the most common malignancy is NMSC with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for the liver recipient
the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC.
Conclusion
The study has not only shown the occurrence of de novo malignancy following organ transplantation, but it has also demonstrated the incidence rate of various malignancies in different types of organ transplantation and the possible etiology or association responsible for the malignancies.
The level of evidence is 2
Drawbacks of registry data
there is a lack of active follow up
the intended design may not lead to an outcome of a certain quality
1. Introduction Malignancy post organ transplantation is an established complication. The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater . In this particular study and for the first time they compared the incidence of de novo postranspalnt cancers to the incdence in the general population and also compared the incidence following different organ transplants. Aim of the study: -Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs. Method: This is a cohort study, this data was taken from NHS registry and other consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007. Result: 37617 transplants 25 104 (67%) received a kidney, 18% alive 10% heat, 57% lung follow-up period 16 years. 5706 patients 15% developed cancer in this period. In 3276 patients first cancer registered of 426 developed a different de novo cancer. Transplant population cancer incidence is twice that general population. 2. What is the level of evidence provided by this article?
Level of evidence: Level 2 – retrospective cohort study
3. What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
1 Variable quality of the data.
2 lost to follow-up on long-term
3 Lack of control group
4 Bias due to heterogeneity of data
article is based on UK population
shows incidence of cancer post solid organ transplant
voluntarily reported
may lead to underestimation
SIR of various tumor are shown
all patients with cancer diagnosis within one month of transplant
were excluded, – so pre existing tumour were ruled out
Of the 37 617 transplanted patients, 25 104 (67%) received
a kidney transplant
16 yrs median follow up
15% develop cancer
The overall incidence rate of cancer in the transplanted
population is just over twice that of the general population.
The SIR is particularly high for
nonmelanoma skin cancer, cancer of the lip and Kaposi
sarcoma.
SIR is highest in lung transplant
in liver transplant , NMSC and lip cancer is less compared to other cancer
following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney,
oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
SIR is higher for male
SIR generally decreases with age
recipient more than 50 yrs – NMSC and PTLD SIR is high but for other tumour SIR is not high
LIMITATION
incidence rate of cancer may be underestimated as second cancer of same patient is not taken in account
observational study of level 1 evidence
data on immunosuppression is not available
Introduction · A documented impact of organ transplantation and the ensuing immunosuppression is an increased risk of cancer. · It’s important not only to educate the patient prior to transplantation but also to provide a practical method for screening and surveillance throughout the postoperative period
Method · The incidence of de novo malignancies in allograft recipients has been described in this study on the cancer incidence in solid organ transplant recipients in Britain, and occurrences following the transplantation of various organs have been compared. · Using standardized incidence ratios that were matched for age, gender, and time period, incidence rates in the transplanted group were then compared with those in the general population.
Result · In transplant patients, de novo cancer occurs twice as frequently (10 times more frequently) as in the general population, with nonmelanoma skin cancer occurring 13 times more frequently. · The biggest standardized incidence ratios are for nonmelanoma skin cancer, lip cancer, posttransplant lymphoproliferative illness, and anal cancer, however, the incidence of various malignancies varies depending on the organ that was transplanted. · Varied types of transplant recipients and various malignancies show different trends in standardized incidence ratios during the years following the transplant. The ramifications of these findings extend to a countrywide screening program.
Conclusion: · A heart, kidney, or liver transplant recipient’s overall risk of developing cancer is more than twice that of the general population, and a lung transplant recipient’s risk of developing cancer is more than three times greater. · The most prevalent kind of cancer among transplant recipients is NMSC. · Regular NMSC screening, lifestyle adjustments to decrease sun exposure, and regular alcohol surveillance in patients having liver transplants all contribute significantly to the goal of early cancer detection.
2. What is the level of evidence provided by this article? Level II (Retrospective cohort study)
3. What are the drawbacks when we use the registry data? · Variable quality of the collected data, and a lack of active follow-up · Additional work for data collection · Possible changes in the long term (accounting system, classifications) · Possible influence of confounders · Need for external and internal validation of collected data · Often no data monitoring/validation; different local conditions in data collection and submission · Target population depends on external validity (participating healthcare special disciplines) · Non-homogeneous definition and scope of international registry items · Complex data privacy issues · Complete and long-term follow-up remains challenging · Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
Introduction
Malignancy post organ transplantation is an established complication could be associated with certain viral infection or a results long standing immunosupression .
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater .
The incidence of different types of malignancy differs according to the organ transplanted .
Methodology :
The population of this study consists of all patients transplanted in England, Wales
and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
Cancer incidence in the transplant population was compared with the general
UK population using the Standardized Incidence Ratio (SIR) .
Analysis :
1- Number of transplantations : 37 617 with follow up period 16 year
Kidney 67%
Liver 18%
Heart 10 %
Lung 5 %
2- Total number of cancer : 5706 ( 15 % )
NMSC 3276
Other than NMSC 2856 ( 426 have NMSC then develops other malignancy )
3-
The overall incidence rate of cancer in the transplanted population is just over twice that of the general population.
The cumulative incidence for all de novo cancers, excluding nonmelanoma skin cancer, in the transplanted population ten years after transplantation,is 90 per 1000
NMSC is much more common, and the corresponding standardized incidence was 14.4 meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
For kidney transplant recipients, the standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip , PTLP and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients.
The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients.
Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
The incidence of oral cancer in liver recipients is high,
What is the level of evidence provided by this article? 2
What are the drawbacks when we use the registry data?
Introduction
· It is known that organ transplantation and immunosuppression increased risk of de novo cancer.
· It is important to get full knowledge about cancer risk to inform recipient and for screening post transplantation.
Aim of the study
Study the incidence of de novo malignancies in transplant recipients and a comparison of these incidences in different types of organ transplant
Materials and Methods
· all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number
· Those who received a combined heart and double lung transplant were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant were taken to be kidney recipients
· Exclusion of recipients of a pancreas alone and all other multi-organ transplant
Discussion
· The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population and over three times higher in recipients of lung or combined heart and lung transplants
· NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
· The incidence of non-Hodgkin’s lymphoma and kidney cancer was different between countries
· the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC
· The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984
· Breast cancer found to be not increased
Weakness of the study
· lack of complete data on immunosuppression
· There was a difference the induction and maintenance immunosuppression between heart and liver transplantation
· the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded
CONCLUSION
· all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure
· there is no need for any additional breast or cervical cancer screening This is a retrospective cohort study level 2 What are the drawbacks when we use the registry data?
· necessary information may be unavailable
· data collection is not done by the researcher
· confounder information is lacking
· missing information on data quality
· truncation at start of follow-up making it difficult to differentiate between prevalent and incident cases and the risk of data
An increased risk of developing de novo cancer is a well-known complication of solid organ transplantation and the associated with use of immunosuppression.
Non-Melanoma Skin Cancer was the most common malignancy with SIR of 16 especially for renal and cardiac recipient that is 3 times higher than others organ transplants. for all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs.
Results:
-The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants, the incidence of Non-Melanoma Skin Cancer is 13 times that of general population, the incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of immunosuppression induction and avoidance of azathioprine in maintenance immunosuppression because azathioprine increase the risk of skin cancer.
Conclusion:
in conclusion this study helps to determine of post solid organ transplant cancer surveillance, screening programme and protection.
2.What is the level of evidence provided by this article?
This article is a retrospective cohort study.
3.What are the drawbacks when we use the registry data?
Title: Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit Introduction: Organ transplantation is associated with an increased risk of malignancy. It is important to understand the magnitude of the elevated risk and those cancers that are increased in the post-transplant period for adequate counselling and surveillance. Methodology: Collette et al in this prospective cohort study, examined the incidence rate of new onset malignancy in British solid organ transplant recipients and compare with incidence in general population. Incidence rates of malignancies were also compared between the difference solid organ transplantations.
The study participants were 37,617 patients who had first kidney, liver, heart or lung transplants in the UK between 1 January 1980 and 31 December 2007. Five hundred and fifty-three participants who had heart-lung transplantation were classified as lung transplant recipients and 764 with combined pancreas kidney transplant were grouped as kidney transplant recipients. The study participants were followed up from the date of first transplant to the earliest date of first reported de novo malignancy, or date of death within the study period. All study participants who had a cancer diagnosis within one month of transplant were excluded except for the 620 participants diagnosed with post-transplant lymphoproliferative disease (PTLD). Results: Majority of study participants received a kidney transplantation (or simultaneous kidney and pancreas), 25 104 (67%), followed by liver (18%) a liver. Ten percent and five percent received a heart and a lung (or heart/lung) respectively. The median follow-up period was 16 years (interquartile range: 8–26 years). Fifteen percent (5706) developed a cancer in this period. Non-melanoma skin cancer was the first registered cancer following transplantation in 3276 patients out of which 426 were de novo.
At 10 years after transplantation, overall incidence rate was 90/1000 patients which is more than twice the 10-year incidence rate for the population of England which was 36 in the same period. Non melanoma skin cancer has a standardized incidence rate of 14.4 (95% confidence interval: 13.8–15.0).
In the transplanted population, the overall cancer incidence rate is about twice that of the general population. Non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma have exceedingly high standardized incidence ratios (SIR). Lung transplant recipients have the highest SIR overall. Non-melanoma skin cancer has a much lower incidence in liver recipients, likewise the SIR for cancer of the lip in liver transplant recipients is less than half that for other transplant recipients. Generally, lymphoma rates are similar, however, non-Hodgkin’s lymphoma has a higher incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver transplant recipients were noted to have high incidence of oral cancers majorly in those who had alcoholic liver disease.
The SIR for non-Hodgkin’s lymphoma increases to a maximum at 12 months after transplantation for all organ recipients and then declines but varies with other malignancies. After kidney transplantation, the SIR increases for many cancers (non-melanoma skin cancer, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for few (Kaposi sarcoma, leukemia). The SIRs for liver and ovarian cancer increase in the early years after transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer is unchanged.
After liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 24 months of transplantation, and then steadily declines. The SIR for bladder, lung and oral cancer and Hodgkin’s lymphoma, increase over time following heart transplantation whereas those for most other cancers remain stable or decrease.
Generally, SIRs for each cancer decrease with increasing age, and higher rates in males. However, NMSC and PTLD in recipients aged over 50 are similar to general population.
Body mass index and commencement of dialysis had no effect on the hazard of cancer. The incidence of non-melanoma skin cancer in kidney transplant recipients was not affected by the type of immunosuppressive medications used at 3 months post transplantation. Conclusion: This is first detailed registry study of pattern of post transplantation malignancy cancer in British transplant recipients. It revealed the varying patterns of cancer occurrence in recipients of different organ types. The overall incidence of non-melanoma skin cancer (NSMC), in recipients of a heart, kidney or liver, is more than double that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and more than triple in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the commonest malignancy, risk is 16 times higher in kidney and cardiothoracic transplant recipients compared with the general population, but 3 times higher risk in liver transplant recipients. Limitations in reporting of cases of malignancies and early treatment of skin lesions might have reduced the reported incidence rates of skin malignancies. Likewise, in the general population, new onset skin cancers may also be underreported.
Liver recipients have a lower incidence of cancer of the lip and anal canal which may be as a result of the lower immunosuppressant dose in transplant protocol.
Level of evidence is 2
Limitation
Lost dataPoor reporting of casesIt is disease specificIt requires resources for data entering and storage over time.
Introduction:
increased risk of de novo cancer is a well known complication of organ transplantation. It is paramount to understand this risk and identify these cancers to make transplant candidate aware of the problem ahead of receiving the transplant and allow for the emergence of guidelines to cancer screening in the post transplant period.
In this particular study and for the first time they compared the incidence of de novo postranspalnt cancers to the incdence in the general population and also compared the incidence following different organ transplants. Methods:
They linked the UK transplant registry to registry data of post solid organ transplant cancer informations in the England, separate data for Wales and Scotland using the INH number. This included all patients who received their first kidney, liver, heart or lung transplant between January 1980 and December 2007.This study included 37617 transplanted patients (67%) received a kidney or simultaneous kidney and pancreas,18% a liver,10% heart and 5% a lung or ( heart and lung).The median follow up for this cohort of patients was 16 years ( range 8- 26 years). Statical Methods:
Cancerincidence in the post transplant period was compared to the general population using the Standardized Incidence Ratio (SIR). Results:
During the follow up period 15% developed cancer.The first cancer registered was NMSC
The 10 – year incidence of de novo cancers in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 fold increased. NMSC ,cancer of lip, PTLD and anal cancer have the largest SIR, but the incdence of malignancies differ according to the type of organ transplanted. The overall SIR is greatest for lung transplant recipients. The incidence of NMSC is much less in liver transplant recipients. Lymphoma rates are similar between different organ transplants except for non- Hodgkin Lymphoma has greater incidence in cardiothoracic transplant recipients.
Patterns for SIRs over time since receiving the transplant are different for different types of transplant recipients and for different malignancies.
For each type of cancer the incidence is greater in males than females and increased with increasing age. The risks of developing PTLD in renal transplant increased with duration of follow up.
Regarding impact of IS ,the incdence of NMSC in kidney transplant recipients was not affected by whether azathioprine or MMF was used at 3 months nor was it affected by the use of tacrolimus or cyclosporine. For other types of cancers data was not available. Conclusion:
The results of this study helps developing of post organ transplant cancer surveillance and screening programme.
2 level of evidence:
3. limitations of the study:
The use of regisry data:
A. under estimation of incidence of cancer.
B. Important data missing like the impact of IS treatment on incidence of cancers.
C. Lack of informations regarding other cancer risk factors like cigarette smoking,sun exposure and alcohol D. Lack of actual follow up. what is good about the study:
1. comparing incdence of post transplant denovo cancer with the with that of the general poulation.
2. Lager number of cohort.
3. Longer duration of follow up.
4. Coming up with results that has implications on post organ transplant cancer screening.
-The aim of the study was to compare cancer incidence in “solid organs transplant recipients” to that of general population .
-This Cohort study included 37617 solid organ transplant recipients .
-The study concluded higher incidence of cancer in lung recipients ( 3 times ) , liver , kidney and heart recipients ( 2 times ) compared to general population .
– NMSC, kidney ,Hodgkin’s ,and oesophageal cancers were higher in renal recipients than the general population .
-Non melanocytic skin cancer was Lower in liver recipients than kidney ones due to relatively lower IS protocols .
-Increased incidence of post-transplant lymphoproliferative diseases over the past few years.
Introduction: Post transplant denote malignancies is a well known complication of transplantation ( due to high doses of immunosuppression). Pre-transplant patient counciling about risk of malignancy development and need for post transplant screening and surveillance are crucial. Aim of the study: -Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs. Method: -Cohort study include all solid organ transplant recipients (first liver, heart, lung and kidney transplant) in UK, Wales and Scotland, from 1Jan 1980 to 31Dec 2007. -37617 recipients included who have NHS number. -Combined heart and double lung transplantation considered as lung transplant, combined pancreas and kidney transplantation deal with as kidney transplantation. -Pancreas alone & all other multi organ transplant recipients were excluded from the study. Results: -The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants
-The incidence of NMSC is 13 times that of general population
-The incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of biological induction and avoidance of azathioprine in maintenance immunosuppression
-The most common malignancies occurring in renal transplant recipients in the current study are NMSC, PTLD, lip and anal cancer and RCC, on the other hand the incidence of breast cancer is not increased due to unclear reason and the incidence of cervical cancer also is not higher which may be explained by active surveillance programs. Conclusion: -The study identify patient groups and cancer types, helps in surveillance program, and providing data on counselling pretransplant patients on the risk of malignancy. -All transplant patients should be screened regularly for NMSC, oral and anal cancers, combined with lifestyle changes prevents sun exposure. Limitation: -Absent data about IS protocols. -Underestimation of cancer incidence because it collected data about first de-novo cancer, so second cancer will not be recorded. -Early detection of cancer in such patients does not translate to superior cure. 2.What is the level of evidence provided by this article? -Level of evidence is 2 3-What are the drawbacks when we use the registry data? -The validity and generalizability of the registry. -Absence of an appropriate comparison group. -Variable quality of the collected data. -Lack of active follow-up (which may underestimate rates of adverse events). -NO specific tool exists for assessing the quality of a registry-based study.
This paper uses data from the UK transplant registry and national cancer registries in England, Scotland and Wales to examine the incidence of first-onset of de novo cancer in solid organ transplant patients: liver, kidney (including combined kidney/pancreas), lung (including combined heart/lung) and heart) who received a first transplant between 01.01.1980-31.12.2007. The outcome measured was timing of detection of de novo cancer post-transplant, or in the case of the first cancer being non-melanoma skin cancer (NMSC) the timing of detection of any second NMSC. Results were compared to the general population in the UK using standard incidence ratios (SIR).
The importance of this paper in comparison to previous studies is that it provided a large sample (37 617 transplanted patients) with a well-defined reference population (general UK population). This contrasted previous studies which were restricted either by being smaller studies or single organ type, or which used data from various different countries thereby making the reference general population harder to define. Although registry data is often limited by inherent bias in the available or missing data (see question 3), the authors of this paper hoped their results would be more reliable than studies using international registries such as the Israel Penn International Transplant Tumour Registry (IPITTR) because reporting to the latter is voluntary and likely to contribute to underreporting of true cancer incidence.
There remained, however, significant limitations in the registry data analysed by the authors of this paper and this included unavailability of smoking history for kidney transplant recipients, missing data on increased BMI (an acknowledged risk factor for development of certain cancers) and <50% of patients having available data on the immunosuppression they were taking 3 months post-transplantation.
Key results: · 15% of patients developed a de novo cancer, and approximately half of these patients were registered with a cancer other than NMSC
· 10 years after transplant the incidence of de novo cancer for solid-organ transplant recipients in the UK was more than double that of the general population
· The incidence of NMSC is much higher in the transplant population (SIR 14.4)
· SIRs are also high for Kaposi’s sarcoma and cancer of the lip in transplant patients
· There is some variation depending on the type of solid organ transplant, with, for example, overall de novocancer incidence being highest in lung transplant recipients and lower rates of NMSC in liver transplant recipients
· For kidney transplant recipients, they have higher SIRs of the following cancers: NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach
· Undergoing solid organ transplant at a younger age is linked to a higher risk of developing de novo cancer compared to an age-matched general population, whereas after the age of 50 the incidence of de novo cancer (excluding NMSC and PTLD) is more similar to that of the general population
· The incidence of breast cancer was not increased in the transplant population
2)What is the level of evidence provided by this article?
This article is a retrospective cohort study which according to the hierarchy of evidence provides a higher level of certainty than case-control studies, case reports and expert opinion but is nevertheless inferior to randomised controlled trials and systematic reviews.
3)What are the drawbacks when we use the registry data?
Post-transplant malignancy is a recognised long-term complication of solid-organ transplantation, with efforts to determine the standardised incidence ratio (SIR) being relevant to pre-transplant patient counselling, determination of optimal treatment protocols and informing surveillance/screening programmes. Given the relatively low incidence of post-transplant malignancy overall, registry data offers the obvious advantages of providing a large cohort reflecting multi-centre experience and is the method of choice for many studies examining incidence of rare phenomena on a population level. However, as attractive as the large data set may initially seem, it comes with several disadvantages and may lead to inherent bias. Some of these disadvantages can be seen within this article:
1. Incomplete data entry which might lead to unintended bias e.g. – Under-reporting of incidence of certain type of cancer – Missing information on population demographics e.g. smoking history – Data entry from some centres may be incomplete – It may be hard to establish a truly comparable control group e.g. the ‘normal population’ for comparison in this article was taken from national cancer registries where incidence of skin cancers may be significantly under-reported – Forms which require coded entries may lead to various interpretations by different people entering data- the registry data may not be truly standardised
2. Retrospective analysis with study findings potentially being restricted by the type of data collected in the registry and additional detail cannot be easily accessed e.g. for this particular article it was not possible to collect data on the immunosuppression used in those patients who had developed cancers
3. Analysed data often spans large timeframe during which there might have been significant changes in the management of patients (e.g. immunosuppression protocols, screening programmes)- deciding which timeframes to include/exclude can potentially result in misleading conclusions
4. Looks at observational data which is often analysing association but does not provide evidence for cause and effect
Numerous studies have investigated cancer incidence in recipients of a kidney, liver or cardiothoracic organ, but these often focus on a single transplant type, a specific form of malignancy, experience at a single center, or a limited duration of follow-up. National studies, based on registry data, have been reported for kidney transplant recipients in Canada , Sweden , Japan , Finland ,Australia and the USA
This first detailed registry study of cancer occurrence in British transplant recipients has shown evidence of different patterns of cancer occurrence in recipients of different organ types. The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
The incidence rates of many cancers that we are reporting for theUKare similartothosereportedbyCanada, Australia and Sweden, but there are also some important differences. We have found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to the UK. The incidence rates for a number of cancers reported in the US study ,are considerably higher than those found in other countries. In particular, the high rates of hepatobiliary, pancreatic, prostate, kidney, uterine and cervical cancer have not been seen in the UK.
Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens. Cigarette smoking, for example, may contribute to the requirement for lung transplantation (emphysema) or heart transplantation (ischaemic cardiomyopathy), while also being associated with an increase in risk of many cancer types. Primary sclerosing cholangitis may require liver transplantation, but is also associated with colitis, which might account for the increase in incidence of cancer of the colon and rectum; likewise alcohol (and the exposure to cigarette smoking which accompanies it) may account for the higher risk of oral cancer in liver recipients
As expected the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC. The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
One cancer whose incidence is not increased in our study, and indeed which may be less common, is breast cancer. The reason for this is not clear, but the finding is consistent with data from an earlier report from the Collaborative Transplant Study registry (recipients between 1983 and 1994 from Europe and North America) but not the most recent US analysis (recipients 1995–2001) in which the incidence of breast cancerwas twice that of the normal population, a similar rise to that noted with other cancers
Aweakness of the study is the lack of complete data on immunosuppression. Heart transplant recipients have generally received biological agents such as antithymocyte globulin for induction with higher levels of calcineurin inhibitor (CNI) based triple therapy than recipients of other organs. In contrast, liver recipients receive a lower immunosuppressive burden using protocols, which involve tapering to CNI monotherapy (usually tacrolimus) in all but autoimmune liver disease.
Studies such as ours identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy. Following transplantation, our study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure However, there is no need for any additional breast or cervical cancer screening.
What is not so clear is how to manage the increased risk of other cancers, which, in spite of having a higher incidence than the normal population, are uncommon
Also uncertain is whether the benefits of early cancer detection in this immunosuppressed population translate into superior cure rates.
1. Please summarize this article.
The main aim of this article is to compare with general population and risk of developing of de-novo malignancy post-transplantation.
Post-transplant tumor incidence is twice as compared to general population and nonmelanoma skin cancer being risk 13 times more compared to normal population according to nomenclature.
The overall incidence rate of cancer post-transplant is 90/1000, the lymphoma incidence has increased 9 folds since 1980-1984.
This study data was taken from NHS registry and other countries that consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007.
The pattern and incidence ratios over time increases and differ for different types of transplant recipient and tumors.
In this article the data were taken from NHS blood and transplant registry of different countries, in the recipient ten year incidence of denovo tumor was twice that of general population.
The incidence of cancer post-transplant was compared to general population using standardized incidence ratio that were gender, age and time period matched. Statistical Method;
This is a cohort study, this data was taken from NHS registry and other consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007.
The data was information of cancer was obtained from age, gender, and time of cancer occurrence.
Following transplantation the pattern of cancer incidence have been evaluated by further stratifying the SIRS and P- values for testing the hypothesis were 1.0 obtained. Results; The total number of patients were 37617, of them 67% received both kidney+ pancreas, 18% a liver, 10% received heart, and 5% a lung. The median follow up period 16 years, out of these recipients total 15% (5706) developed a cancer, the de novo cancers 426 developed skin cancer and 2856 were registered with nonmelonoma skin cancer.
Impact of initial use of immunosuppression;
There was no any association of NMSC in immunosuppression in first three months, otherwise insufficient data about other cancers.
Discussion;
The British transplant detailed registry study evidence showed there is occurrence of cancer in different pattern in transplant recipient in different organ types.
NMSC was the most common malignancy with SIR of 16 especially for renal and cardiac recipient that is 3 times higher than that of others.
The incidence is equal many centers like Sweden and Australia with few differences like they found higher incidence of certain cancer in different countries. They did not found any certain association of risk factor.
Limitation;
There was lack of detailed information about immunosuppression.
Induction was different for heart transplantation and different for other organs.
Maitianence immunosuppression was higher for heart transplantation.
The first cancer incidence occurrence except NMSC was not recorded.
This is a longitudinal observational cohort study than include all UK post transplant patients from 1980-2007(NHSBT), comparing the incidence of De novo malignancy in SOT to general population by using SIR(Standardized Incidence Ratio) 10 years incidenceof De novo malignancy in post transplant Solid Organ was two times higher than general papulation with NMSC the most common form of malignancy.
What is the level of evidence provided by this article?
Level 2(retrospective cohort study)
What are the drawbacks when we use the registry data
Summary of Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry AuditIntroduction:-
Most of the studies’ incidences of cancer in recipients focus on a single transplant type, a specific type of malignancy a single center, or a limited duration of follow-up.
Registries, such as that of the intentional society of heart and lung transplantation, cover a number of countries, so it is not clear what the referral population should be.
This is the first repeat national study of de novo malignancy in British solid organ transplant recipients that make compassion with the incidence rate in the general population and compare this incidence following the transplantation of different organs. Methods and material
The cohort consists of 37 617 transplant patients with known age and gender at transplantation patients were followed up from the date of first transplant to earliest of the date of first repeat de novo malignancy a date of death within the study period. Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the standardized incidence ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study chart to the expected number in the general population. Results
37617 transplants 25 104 (67%) received a kidney, 18% alive 10% heat, 57% lung follow-up period 16 years.
5706 patients 15% developed cancer in this period.
In 3276 patients first cancer registered of 426 developed a different de novo cancer.
Transplant population cancer incidence is twice that general population.
The standardized ratio is high for non-melanoma skin cancer such as the hip and Kaposi sarcoma impact of initial immunosuppression.
The incidence of NMSC in Kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor unaffected by the use of TAC or ciclosporin. Discussion
This first detailed registry study of cancer occurrence is the British transplant recipient has shown evidence of different patterns of cancer occurrence in recipients of different organ types.
Some diseases for such transplantation is undertaken may be associated with malignancy elsewhere as aggregate smoking, primarily sclerosing cholangitis and analgesic nephropathy.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukemia and lung cancer.
A liver transplant has a higher risk of skin cancer with increasing age. The level of evidence
level 2 What are the drawbacks when we use the registry data?
Heterogenous data collection with retrospective studies
Follow-up on long-term participation was lost.
Variability of quality of data.
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression.
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease.
the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower.
For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs. Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia). The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily. In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease. The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients. This increased incidence may be an underestimate since reporting of skin cancers may not be complete because some lesions will be removed or ablated without histological confirmation and some of the cancer registries did not collect data on basal cell carcinomas.
☆Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit.
▪︎This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Introduction: ▪︎An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression.
◇Results: ▪︎This study on cancer incidence in solid organ transplant recipients in Britain, described the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs. ▪︎Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales. ▪︎Incidence rates in the transplanted population were compared with the general population, using standardized incidence ratios matched for age, gender and time period. ▪︎The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. ▪︎Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. ▪︎These results have implications for a national screening program
◇ Weaknesses f the study: ▪︎The lack of complete data on immunosuppression. ▪︎It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded. ▪︎The increased risk of cancer in transplant recipients is a reflection of being immunosuppressed rather than being attributable to any particular drugs, ◇ The strength of this study: ▪︎Identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy. ▪︎ It confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure. However, there is no need for any additional breast or cervical cancer screening.
◇ Important recommendations of the study: ▪︎Patients undergoing liver transplant for alcohol should have regular surveillance of the aerodigestive tract. ▪︎Patients with primary sclerosing cholangitis who have their colon and rectum in situ should undergo regular colonoscopy. ▪︎The presence of recurrent graft cirrhosis should also be a cue to regular ultrasound surveillance for hepatocellular carcinoma. ▪︎Similarly a case can be made for subjecting renal transplant recipients to regular US of their transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination.
☆Level Of evidence: II
☆Drawbacks of regisrry data 1. Variable quality of the collected data 2. Lack of active follow up(which may undestimate rates of adverse events 3.The intended design does not automatically lead to study of a certain quality.
Please summarise this article Introduction
Previous studies have investigated cancer incidence in recipients of a specific organ (kidney, liver or cardiothoracic organ), and often focus on a single transplant type, a specific form of malignancy, in a single center, or with limited duration of follow-up
This is the first study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs Materials and Methods
All patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant (between 1 January 1980 and 31 December 2007)
Combined heart and double lung transplant were regarded as lung transplant recipients. Combined pancreas and kidney transplant were classed as kidney recipients
Exclusions were pancreatic transplant alone and all other multi-organ transplant recipients
The study consists of 37 617 transplanted patients with known age and gender at transplantation. Follow- up of patients was from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death
The median follow up period was 16 years Results
Total Of 37617 transplanted patients were included (67% received a kidney or simultaneous kidney and pancreas, 18% a liver, 10% a heart and 5% a lung or heart/lung)
15% developed a cancer [the first cancer was NMSC (3276 patients)]
The 10-year incidence of de novo cancer in transplant recipients is over twice that of the general population
NMSC is much more common (over 14 times that of the general population)
The SIR are particularly high for nonmelanoma skin cancer, cancer of the lip, PTLD and anal cancer, but the incidence of different types of malignancy differs according to the organ transplanted
The incidence of NMSC in kidney transplant recipients was unaffected by the type of immunosuppression medication Discussion
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients (which is three times higher than that for liver recipients)
No increase risk of breast cancer Weakness of the study: the lack of complete data on immunosuppression. Induction and maintenance immunosuppressant is different from organ to organ (Heart transplant recipients have generally received biological agents such as antithymocyte globulin for induction with higher levels of calcineurin inhibitor (CNI) based triple therapy whereas in liver recipients receive a lower immunosuppressive burden using protocols, which involve tapering to CNI monotherapy (usually tacrolimus) in all but autoimmune liver disease What is the level of evidence provided by this article?
Retrospective cohort study (level II) What are the drawbacks when we use the registry data?
1. incomplete recording
2. reporting of cancers may not be complete
3. lack of complete data on immunosuppression
4. loss of follow-up
5. different protocol of immunosuppressions
This study depended on linked data between UK Transplant Registry and cancer registrations following solid organ transplantation in England , Wales and Scotland. This study cohort consists of 37 617 patients transplanted who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007. A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC (C44), and 2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer. Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients. NMSC is much more common with a risk of over 14 times that of the general population. For kidney transplant recipients, the overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The overall standardized incidence ratios are greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower. For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs. Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia). The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant. Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily. In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease. The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer. The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population. For each of the types of cancer shown, the hazard of occurrence is greater in males than females, and increases with increasing age. The risks of developing PTLD and kidney cancer have increased over the study period. Body mass index, and whether or not a patient was on dialysis at time of listing for transplantation, where available, did not significantly affect the hazard of cancer after adjusting for the factors . For recipients of a liver, recipient age group and primary disease affected the risk of skin cancer (p < 0.001 and 0.01, respectively) and colorectal cancer (p = 0.06 and 0.002, respectively). The risk of PTLD only depended on recipient gender (p = 0.02), and the risk of lung cancer depended only on recipient age group (p = 0.02). For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients (p = 0.004Impact of initial immunosuppression From the available data, the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data for reliable estimates 1. What is the level of evidence provided by this article? level 2 2. What are the drawbacks when we use the registry data?
some information will be missed and they could be a source of bias (selection, information or confounding)
Objective
In this cohort study they include Data on transplant recipients in the UK Transplant Registry, and the separate registries for Wales and Scotland, using the NHS number. The data selected between 1 January 1980 and 31 December 2007 Methods
In this cohort they use the Standardized Incidence Ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population. Results :
The cumulative incidence rate of cancer in the transplanted population is just over twice that of the general population. And further increasing with increasing the duration of transplantation The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma he incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 folds higher in recipients of lung or combined heart and lung transplants Regarding NMSC The is 13 times that of general population
Regarding renal transplant recipients in the current study are NMSC, PTLD, and RCC. Conclusion
Malignancy is more frequent in solid organ transplantation and its frequency depends on many factors including the organ transplanted and type pf malignancy level of evidence
II What are the drawbacks when we use the registry data?
Additional work for data collection – Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders
– Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission
– Target population depends on external validity (participating healthcare special disciplines) – Non-homogeneous definition and scope of international registry items
– Complex data privacy issues
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization
Please summarise this article Summary:
-An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
-It is the first detailed registry study of cancer occurrence in British transplant recipients which shown evidence of different patterns of cancer occurrence in recipients of different organ types. The overall incidence of cancer (excluding
NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population , and over three times higher in recipients of lung or combined heart and lung transplants .
– It is cohort study consists of 37 617 transplanted patients with known age and
gender at transplantation. Patients were followed up from the date of first
transplant to the earliest of the date of first reported de novo malignancy,
or date of death within the study period.
-NMSC is the most common malignancy for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
– Liver recipients appear to be relatively protected against cancer of the lip and anal canal, diseases which, like NMSC, which may reflect lower doses of maintenance immunosuppression, in particular avoidance of azathioprine and the absence of biological induction agents in UK liver transplant immunosuppressive protocols.
-They have found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to
the UK.
-There is no high rates of hepatobiliary, pancreatic, prostate, kidney, uterine and
cervical cancer in the UK.
-Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens. For example, Analgesic nephropathy or aristolochia use may necessitate renal transplantation, while being associated with transitional cell carcinoma of
the native urothelium .
-As expected the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC.
-The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
-The other cancer whose incidence is clearly increasing in renal transplant
recipients over the study period is renal cell carcinoma. The reason for this is not clear, but may in part reflect the increasing age of the recipient in whom renalmalignancy is more common and in part the occurrence of cancer in acquired cystic disease of the native kidneys .
-One cancer whose incidence is not increased in the study is breast cancer.
– Another tumor whose incidence might be expected to be higher is cervical carcinoma, since it is known to be a consequence of papilloma virus infection .
–Limitations :Aweakness of the study is the lack of complete data on immunosuppression.
-It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be
recorded. What is the level of evidence provided by this article?
Level 2 What are the drawbacks when we use the registry data?
-Incomplete and inadequate data collection.
-Incomplete follow- up.
the incidence of malignancy in post-transplant recipient is higher as compared to general population. Different types of cancers are more common in different types of organ transplantation. this study tried to identify different cancers occurring in various organ transplant patients.
Many studies occurring nationally and internationally has their limitations of small sample size and short follow-up.
this study showed that incidence of malignancy among transplant patients were twice as compared to non-transplant population in UK.
This incidence may vary according to the transplanted organ, however common cancers found are non-melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
the SIR for cancers was higher for lung transplant patients. the incidence
In general, for all transplant recipients, the risk of cancer was higher in males than females and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
However, with all this data, it is still unclear how to manage increased risk of cancer. It is also yet unknown how significant the impact of early cancer detection is on superior cure rates in this immunosuppressed population.
Level of evidence
This is a retrospective cohort study, and hence, level of evidence 2.
What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
a) Variable quality of the data.
b) lost to follow-up on long-term
c) Lack of control group
e) Bias associated with the data collection
f) Underestimation of the prevalence/ incidence rates due to underreporting
Summary
This is a retrospective descriptive study that analysed the incidence of malignancy in solid organ recipients between 1980 and 2007 in the UK data registry. They included recipients who received a first kidney transplant, liver, lung and heart, and excluded pancreas and multi organ recipients. The sample size was large with 37,617participants with 67% of them being kidney transplant recipients.
Overall transplant recipients were twice at risk to develop malignancy in comparison to general population. The immediate post-transplant period (<3years) is associated with high SIR for liver and lung recipients.
Kidney transplant recipients had increased risk for NMSC, lip, Kaposi sarcoma, NHL and anal cancer. Liver transplant recipients had lower risk of NMSC at 6 .0 in comparison to other organ recipients, however they had higher risk of oral cancers. Lung transplant recipients had the highest incidence risk at 3.6, and were at the highest risk of developing NHL.
Factors affecting included gender and increased age for kidney transplant recipients, and age and prior diagnosis for liver transplant recipients; of note the type of immunosuppression did not affect the incidence of NMSC in kidney transplant recipient.
The major strength of the study was that it had a large sample size, however being a descriptive study it was not able to test for any associations. The study was done only in the UK thus may be difficult to generalise to other populations.
Level of evidence 3
Drawbacks when using registry data
Incomplete/ missing data
Lack of active followup
Selection bias
The incidence of de novo malignancy is soaring post transplantation and immunosuppression with most common tumors encountered are non-melanotic skin cancer with incidence levels at 13 times higher than general population. Anal cancer, post-transplant lymphoproliferative disease of either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma variants and lip cancers are the most prevalent types of post transplantation with 10 years incidence rate double the one in general population.
However, the incidence and type of malignancy is variable according to the kind of organ transplantation.
To verify this notion a retrospective observational study was conducted to assess the incidence and type of malignancy commonly linked to each allograft type in a cohort of patients observed from 1980 through 2007, consist of 37617 patients 67% kidney transplant recipient,18% a liver ,10% heart and 5% lung transplant. Results:
5706 developed cancer of whom 2856 developed non melanoma skin cancer.
After transplantation all patients should undergo regular screening for non melanoma skin cancer particularly lip and anal cancer. That has to be concomitant with life style modification and sun light avoidance.There is no indication to increase screening rate for breast cancer and cervix cancer. In patients with liver transplant , digestive system screening , has to be done regularly. similarly, patients with primary biliary sclerosis , should have regular colonoscopy screening.Kidney transplant recipient must have an ultra sound screening of native kidneys for malignancies particularly in those with analgesic nephropathy and Aristolochia-related interstitial nephritis as its indicative to assess cystoscopically the urothelium. Level of evidence :
of registry based study is 3 , as its retrospective study in general. Draw backs of registry data studies :
1) the level of data is not consistent through out the cases registered
2) the criteria for diagnosis is not standardized.
3) No follow up data and no confirmatory information
4) No control population.
5) collection is influenced by other parties
Kidney transplant recipients have a higher rate of malignancies, so this study examined and compared the rates after different organ transplants.
methods and materials:
This study included data from 10 cancer registries (8 from England, 1 from Wales, and 1 from Scotland) from 1980 to 2007. 37,617 first-time kidney, liver, heart, or lung transplant recipients were included.
All patients transplanted in England, Wales, and Scotland between 1 January 1980 and 31 December 2007 who got their first kidney, liver, heart, or lung transplant and had an NHS number are included in the study cohort.
To code new malignancies, the Cancer Registries utilize histology and other vital information, such as cross-sectional imaging.
To exclude cancers that may have been prevalent at the time of transplantation, all patients diagnosed with cancer within one month of transplant were excluded, with the exception of 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD).
results :
– The median follow-up time for this sample was 16 years,5706 patients (15%) developed cancer.
– 3276 patients developed NMSC after transplantation.
– 2856 patients had de novo cancers other than non-melanoma skin cancers.
– Receivers have a 90 per thousand incidence rate 10 years after transplantation.
– Two years after transplantation, this relative risk remains constant. NMSC is substantially more common, and the standardized incidence was 14.4, implying transplant recipients had over 14 times the risk of this kind of cancer.
– Nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma have high SIRs.
– Lung transplants have the highest SIR.
– Liver transplant recipients have lower rates of non-melanoma skin cancer and lip cancer.
– Non-lymphoma Hodgkin’s SIRs peak one year after transplantation and thereafter fall for all organs.
limitations:
incomplete details regarding immunosuppression.
The study has omitted a recipient at the first occurrence of any cancer (excluding NMSC), therefore if a recipient acquired second cancer, this would not be recorded, which means the cancer incidence rates in this study are likely underestimates.
strength:
big population
median follow-up 16 ys
What is the level of evidence provided by this article?
Level 2, observational longitudinal cohort study
What are the drawbacks when we use the registry data?
– follow up may be lost in long term
– underreporting leads to underestimation
– bias due to heterogeneity of data
Summary:
This study compares the incidence of de novo malignancy in solid organ transplant recipients with general population using the Standardized Incidence Ratio (SIR). It is an observational longitudinal cohort study and includes all UK transplant patients (NHSBT data) from 1980 to 2007, but patients with diagnosis of cancer within one month post-transplant were excluded. The median follow up period of this study was 16 years. The 10-year incidence of de novo malignancy in post-transplant patients was twice that of general population with non-melanoma skin cancer being the commonest. Other common cancers were cancer of the lip, Kaposi sarcoma, PTLD, anal cancer and kidney cancer. Level of evidence: Level 2 What are the drawbacks when we use the registry data? Lack of follow-up Limited amount of data Selection bias.
Q1: Is it a longitudinal study or a cross sectional study? A 2: It is a longitudinal study. Q2: We know that it is a longitudinal study. Is it a cohort study or case control study? A 3: Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies (that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary). Conclusion: This is an observational longitudinal cohort study
Aim of the study: (UK registry audit) Compare incidence of de novo malignancy in solid organ transplant with general population and compere these incidences with different organs in the British population.
Type of study: retrospective observational case control study Population: Inclusion: All UK transplant (NHSBT data) from 1980 to end of 2007. Exclusion: Pancreas alone and all other multi-organ transplant recipients. All patients with cancer diagnosis within one month of transplant were excluded, those with PTLD diagnosis.
Exposure: patient who had solid organ transplant
Control: general population
Outcome: Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR).
Method: NHSBT data were linked with data made available by the cancer registries in England, Scotland and Wales. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Analysis: adjusting for confounders: age group and gender, primary disease, smoking history, obesity, dialysis
Results:
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years). The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer (NMSC) being 13 times greater than general population for all organs. Most common cancers: NMSC (17), cancer of the lip (66), Kaposi sarcoma (17), PTLD (7-12) and anal cancer (10), kidney (8) have the largest SIRS. (Fractions removed to nearest number, figures for kidney Tx). Patterns in SIRs over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. Pattern with time: Non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines (Key figure attached)
Strength:
Excellent study to help counselling the patient before transplant for shared decision making and help stratification therefore increased awareness of cancers. Very big population
Negatives from the autors:
Missing data, to overcome they had to use statistical model.
Less aggressive protocol available with development of antimicrobials which can help reducing SIRs
Renal cancer: registries do not distinguish between cancers arising in the native kidneys or in the transplant, and it is possible that the increase in incidence also reflects the aging donor population who may have an unrecognized renal cancer at the time of Tx.
lack of complete data on immunosuppression.
The study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded. Therefore, the SIRs may be underestimate.
Negatives from my opinion: Population in the study: They did not adjust for ethnicity which OI believe big drawback specially the UK population is more diverse, and the nonwhite population is growing up. The current British population is changing therefore SIRs (either transplant and general) may have changed. (REF below)
An increased risk of cancer is a well-known complication of organ transplantation and the associated immuno-suppression.
The authors describe the incidence of de novo cancers in allograft recipients and compare these incidences to those following organ transplantation in this study on cancer incidence in solid organ transplant recipients in the United Kingdom.
Data from the NHS Blood and Transplant (NHSBT) UK Transplant Registry were linked with cancer registry data from England, Scotland, and Wales. The transplanted population’s incidence rates were then compared to the general population’s using standardized incidence ratios that were age, gender, and time period matched.
In transplant recipients, the 10-year incidence of de novo cancer is twice that of the general population, with nonmelanoma skin cancer being 13 times more common. The most common standardized incidence ratios are for nonmelanoma skin cancer, cancer of the lip, post-transplant lymphoproliferative disease, and anal cancer, but the incidence of different types of malignancy varies depending on the organ transplanted.
The patterns in standardized incidence ratios over time after transplantation differ for different types of transplant recipients and malignancies. The implications of these findings for a national screening program are significant.
Results
25 104 (67%) of the 37 617 transplanted patients received a kidney (or both the kidney and the pancreas), 18% a liver, 10% a heart, and 5% a lung (or heart and lung). The median follow-up period for this patient group was 16 years (IQR: 8–26 years).
During this time, 5706 patients (15%) developed cancer. The first cancer registered in 3276 patients after transplantation was an NMSC, and 426 of these were later registered as having developed a different de novo cancer. As a result, 2856 patients were identified as having a de novo cancer other than nonmelanoma skin cancer.
Total new cancer incidence (excluding nonmelanoma skin cancer):
Recipients have an overall incidence rate of 90 per 1,000 patients ten years after transplantation, which is more than double the 10-year incidence rate for the English population, which was 36 in the same period. This overall relative risk remains relatively constant for the first two years following transplantation. NMSC is much more common, with a standardized incidence of 14.4 (95% confidence interval: 13.8-15.0), implying that the risk of developing this type of cancer in a transplant recipient is more than 14 times that of the general population.
The overall cancer incidence rate in the transplanted population is slightly higher than in the general population. The standardized incidence ratios (SIR) for nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma are especially high.
Lung transplant recipients have the highest overall SIR.
The incidence of NMSC in liver transplant recipients is much lower, and the SIR for lip cancer in these patients is less than half that of other transplant recipients.
Lymphoma rates are comparable, with the exception of non-Hodgkin lymphoma, which is more common in cardiothoracic transplant recipients.
Although the incidence of oral cancer in liver recipients is high, 15 of the 18 observed cases occurred in those whose primary disease was alcoholic liver disease.
Time trends following transplantation
When compared to the general population, the incidence rate quickly rises to twice that of the general population following kidney or heart transplantation.
The SIR after lung transplantation rises dramatically at first, then falls over time. For liver recipients, the pattern is similar, though the SIR is generally lower.
The SIR for non- Hodgkin’s lymphoma increases to a maximum one year after transplantation and then declines across all organs, but patterns in the incidence rates of many other malignancies vary by organ.
The SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus, and stomach) and decreases for others after kidney transplantation (Kaposi sarcoma, leukaemia).
SIRs for liver and ovarian cancer rise immediately after transplantation and then fall, whereas SIRs for breast, pancreas, and uterine cancer remain constant.
The SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreas) peaks within two years of liver transplantation and then steadily declines.
The SIR for bladder, lung, and oral cancer, as well as Hodgkin’s lymphoma, increases over time in heart transplant recipients, whereas those for the majority of other cancers remain stable or decrease.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukaemia and lung cancer.
The SIRs for each cancer generally decrease with increasing age, and many of the rates are higher in men than in women.
Other than NMSC and PTLD, the incidence of cancer in recipients over 50 is not significantly higher than in the general population.
The study’s weaknesses:
-the lack of comprehensive data on immunosuppression.
-The cancer incidence rates are likely to be under-estimated because the study censored recipients at the first occurrence of any cancer, so if a recipient developed a second cancer, it would not be recorded.
========================== 2. What is the level of evidence provided by this article?
Registry-based studies are typically classified as Level II or III in the evidence-based medicine hierarchy.
========================== 3. What are the drawbacks when we use the registry data?
The limitations of registries include:
Variable data quality
Lack of active follow-up (which may underestimate rates of adverse events).
The intended design, like any other study type, does not guarantee a high-quality study.
There is no specific tool for assessing the quality of a registry-based study.
An increased risk of cancer is a well-known complication of organ transplantation and the associated immuno-suppression.
The authors describe the incidence of de novo cancers in allograft recipients and compare these incidences to those following organ transplantation in this study on cancer incidence in solid organ transplant recipients in the United Kingdom.
Data from the NHS Blood and Transplant (NHSBT) UK Transplant Registry were linked with cancer registry data from England, Scotland, and Wales. The transplanted population’s incidence rates were then compared to the general population’s using standardized incidence ratios that were age, gender, and time period matched.
In transplant recipients, the 10-year incidence of de novo cancer is twice that of the general population, with nonmelanoma skin cancer being 13 times more common. The most common standardized incidence ratios are for nonmelanoma skin cancer, cancer of the lip, post-transplant lymphoproliferative disease, and anal cancer, but the incidence of different types of malignancy varies depending on the organ transplanted.
The patterns in standardized incidence ratios over time after transplantation differ for different types of transplant recipients and malignancies. The implications of these findings for a national screening program are significant.
Results
25 104 (67%) of the 37 617 transplanted patients received a kidney (or both the kidney and the pancreas), 18% a liver, 10% a heart, and 5% a lung (or heart and lung).
The median follow-up period for this patient group was 16 years (IQR: 8–26 years).
During this time, 5706 patients (15%) developed cancer.
The first cancer registered in 3276 patients after transplantation was an NMSC, and 426 of these were later registered as having developed a different de novo cancer.
As a result, 2856 patients were identified as having a de novo cancer other than nonmelanoma skin cancer.
Recipients have an overall incidence rate of 90 per 1,000 patients ten years after transplantation, which is more than double the 10-year incidence rate for the English population, which was 36 in the same period.
This overall relative risk remains relatively constant for the first two years following transplantation.
NMSC is much more common, with a standardized incidence of 14.4 (95% confidence interval: 13.8-15.0), implying that the risk of developing this type of cancer in a transplant recipient is more than 14 times that of the general population.
The overall cancer incidence rate in the transplanted population is slightly higher than in the general population. The standardized incidence ratios (SIR) for nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma are especially high.
Lung transplant recipients have the highest overall SIR.
The incidence of NMSC in liver transplant recipients is much lower, and the SIR for lip cancer in these patients is less than half that of other transplant recipients.
Lymphoma rates are comparable, with the exception of non-Hodgkin lymphoma, which is more common in cardiothoracic transplant recipients. Although the incidence of oral cancer in liver recipients is high, 15 of the 18 observed cases occurred in those whose primary disease was alcoholic liver disease.
Time trends following transplantation
When compared to the general population, the incidence rate quickly rises to twice that of the general population following kidney or heart transplantation.
The SIR after lung transplantation rises dramatically at first, then falls over time. For liver recipients, the pattern is similar, though the SIR is generally lower.
The SIR for non- Hodgkin’s lymphoma increases to a maximum one year after transplantation and then declines across all organs, but patterns in the incidence rates of many other malignancies vary by organ.
The SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus, and stomach) and decreases for others after kidney transplantation (Kaposi sarcoma, leukaemia).
SIRs for liver and ovarian cancer rise immediately after transplantation and then fall, whereas SIRs for breast, pancreas, and uterine cancer remain constant.
The SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreas) peaks within two years of liver transplantation and then steadily declines.
The SIR for bladder, lung, and oral cancer, as well as Hodgkin’s lymphoma, increases over time in heart transplant recipients, whereas those for the majority of other cancers remain stable or decrease.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukaemia and lung cancer.
The SIRs for each cancer generally decrease with increasing age, and many of the rates are higher in men than in women.
Other than NMSC and PTLD, the incidence of cancer in recipients over 50 is not significantly higher than in the general population.
The study’s weaknesses:
-the lack of comprehensive data on immunosuppression.
-The cancer incidence rates are likely to be under-estimated because the study censored recipients at the first occurrence of any cancer, so if a recipient developed a second cancer, it would not be recorded.
========================== 2. What is the level of evidence provided by this article?
Registry-based studies are typically classified as Level II or III in the evidence-based medicine hierarchy.
========================== 3. What are the drawbacks when we use the registry data?
The limitations of registries include:
Variable data quality
Lack of active follow-up (which may underestimate rates of adverse events).
The intended design, like any other study type, does not guarantee a high-quality study.
There is no specific tool for assessing the quality of a registry-based study.
I do not agree with your equivocal stance on level of evidence 2 or 3! However, I like your list of limitations and strengths of this registry-based study.
Summary of the article COMPARISON OF THE INCIDENCE OF MALIGNANCY IN RECIPIENTS OF DIFFERENT TYPES OF ORGAN: A UK REGISTRY AUDIT
This retrospective review article, using UK transplant registry in the period between Jan1980 and Dec2007, studied the incidence of malignancy in allograft recipients post-transplantation in comparison to the general population with matching for age, gender and time period. The 10 yrs incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer(NMSC) being 13 times greater. NMSC, cancer of the lip, PTLD and anal cancer have the largest standardized incidence ratios.
Study’s results • The overall incidence rate of cancer, 10 yrs post-transplant is 90 per 1000 patients which is more than twice the rate in the general population. • NMSC is much more common, and the corresponding standardized incidence was 14.4. NMSC is over 14 times that of the general population. • The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma. • Non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. • The incidence of post-transplant lymphoma in kidney recipients has increased ninefold since 1980– 1984. This observation probably reflects the more aggressive immunosuppressive protocols available today. • The incidence rate for breast cancer is not increased in this study, for unclear reason. • The incidence rate of cervical cancer is not increased which may be explained by the active cervical screening program in the UK.
The level of evidence provided by this article?
This is retrospective study, with level of evidence grade 3.
What are the drawbacks when we use the registry data? Registry Disadvantages: • Disease-specific, not longitudinal. limited amount of data for every patient. • Does not include information necessary for billing. • Requires hardware, software, and maintenance. • Requires data entry and data maintenance. • Parallel documentation system (i.e., some information has to be entered in two systems). • Can’t stand alone, must have an additional documentation system. Registry Advantages: • Flowsheet is a powerful tool to monitor clinical data and track trends. • Provides a dashboard of who needs what. • Provides total population data reporting with no chart abstraction. • Generates revenue (it shows when services are needed). • Provides outreach information at fingertips. • Improves team-based care. • Smaller software package than EHRs.
Summarise of this article the aim of this study to know the risks of developing denovo malignancy and compare it with the general pop[ulation. Adding to that, link the type of cancer developed after each type of solid organ transplantation.
They found an increased number of malignancies 12 times after transplantation compared to the general population.In specific, non-melanoma skin cancer had a higher incidence among transplant recipients, a staggering 13 times higher. This incidence may vary according to the transplanted organ, however common cancers found are non-melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
The data were collected from UK registry system, adding to the data registered in cancer centers in Englan , Wels and Scotland.
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL).
The immunosuppression used in the transplant was not properly linked to the type of cancer and was incomplete data and this create sort of bias.
Introduction
Incidence of malignancy among organ transplant recipient are high in comparison to general population and there’s variations in incidence of malignancy with different types of malignancy and associated with different types of organ transplant.
This study done to understand risk factors and identify type of cancer related to specific organ transplant for screening and surveillance in post operative periods.
There’s many studies national and international to identify risk but all of them have bias if underestimation due to small sample and short fallow up.
Methods and Materials:
This cohort study done between 1 January 1980 and 31 December 2007, and how have NHS number, data collected from transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), and linked with cancer information post transplant registration from different countries.
The information of malignancy was obtained from age, gender, time of cancer occurrence but excluded cancer which prevalent at time of transplant or after one month post transplant except lymph proliferation malignancy ( Hodgkin and non Hodgkin’s lymphoma ), histology of malignancy and date of death.
History of smoking and obesity with body mass index was obtained and primary cause of kidney failure and duration of dialysis was collected.
Results:
The incidence of cancer post transplant is low between 1980–1984 because unrecorded of cases at that time.
The median follow up period for this cohort of patients was 16 years.
However, from the total transplant patients only 15% developing cancer.
The incidence of cancer in the transplanted population is double of the general population.
The incidence ratios are high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
Incidence of nonmelanoma skin cancer is much less in liver transplantation.
Lymphoma rates are similar in kidney and liver transplant except non-Hodgkin’s lymphoma incidence is high in cardio thoracic transplant.
For all organ transplant the incidence of non-Hodgkin’s lymphoma is increased in first year post transplant and then decline after that.
For kidney transplant increase in incidence of non melanoma skin cancer and anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach and decreases for Kaposi sarcoma, leukaemia.
For liver and ovarian cancer increase in the years immediately post transplantation and then decline, while breast, pancreas and uterine cancer remain constant.
For liver transplantation, the cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas peaks within 2 years of transplantation, and then declines steadily.
In heart transplant recipients, the bladder, lung and oral cancer, and Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
For lung transplantation; there is less evidence of an increase of leukaemia and lung cancer with time.
Incidence of cancer more in males than females and age groups above 50years in comparison to general population.
There’s insufficient data regarding obesity and use of immunosuppressive therapy in reduce evidence of cancer post transplant. Discussion:
Non melanoma skin cancer is the most common malignancy in kidney transplant.
The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984.
However, This registration not differentiate between native kidney cancer or from transplant organ. There’s no sufficient data on use of immunosuppressive therapy in developing cancer.
This study concluded for counselling pretransplant patients on the risk of malignancy and should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure.
However, there is no need for any additional breast or cervical cancer screening.
What is the level of evidence provided by this article?
Level 2
What are the drawbacks when we use the registry data?
There’s lack of data regarding history of smoking and use of immunosuppressive therapy as part may induce malignancy.
Retrospective studies with heterogeneous in collecting data and poor fallow up.
This article focusses on the development of de novo malignancy in transplant recipients and the comparison with incidence of the same among different organ transplants across the UK.
The study found that incidence of malignancy among transplant recipients is twice the rate compared to incidence among the general population. In specific, non melanoma skin cancer had a higher incidence among transplant recipients, a staggering 13 times higher. This incidence may vary according to the transplanted organ, however common cancers found are non melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
The data used in this study was obtained from two major sources – the UK transplant registry, and cancer registries across England, Wales, and Scotland, regarding cancer among transplant recipients post transplant. The data included kidney, liver, heart, lung transplant, and combined pancreatic-kidney transplants. The majority were kidney transplants, at 67%, followed by liver at 10%.
Immunosuppressive drugs used for the recipients included in the study were Azathiprine, MMF, tacrolimus, and cyclosporin. The data was available only for half of the patients, and only at 3 months post transplant. SAS or statistical analysis software was used for calculations. Comparisons were made based on Cox regression models and adjusted for recipient age group, gender, primary disease, and year of transplant.
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL).
Different factors appeared to affect the incidence of various cancers among these transplant recipients. In general, for all transplant recipients, the risk of cancer was higher in males than females, and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
Incidentally, BMI and prior dialysis did not have a significant effect on cancer incidence in these patients.
Liver transplant recipients were found to be at a higher risk of skin cancer with increasing recipient age and colorectal cancer with history of primary disease.
Lung cancer was highly impacted by recipient age, with PTLD dependent on recipient gender.
Regular ultrasounds, surveillance of aerodigestive tract, and colonoscopy can be done for transplant recipients, to detect changes in favor of liver, lung, colon, kidney, or anal cancer. How helpful this is toward long term outcome is yet to be seen.
However, with all this data, it is still unclear how to manage increased risk of cancer. It is also yet unknown how significant the impact of early cancer detection is on superior cure rates in this immunosuppressed population.
Level of evidence
This is a retrospective cohort study, and hence, level of evidence 2.
Drawbacks
Incomplete data – most importantly for immunosuppressive regimen which forms an important part in cancer incidence in transplant recipients. Selection bias
This study recruits data between 01st Jan 1980 and 31st Dec 2007 from Britain registry comprising 37 617 transplanted patients and highlights the incidence of De-novo cancer in solid-organ-transplant recipients in comparison to age and gender matched general population . Counseling about the increase chances of malignancies post-transplant due to immunosuppressive medications, and development of screening and surveillance program for early detection.
The study stated that 5706 patients (15%) developed cancer in the median follow up period of 16 years and the most common malignancy which occur post-transplant is NMSC , occurring with a frequency of 14 times more compared to general population .The malignancies which occur two times more are those occurring in renal, heart and liver transplant recipients ,however, chances of malignancy are low in liver transplant recipients due to minimum doses of immunosuppression and no induction therapy being used. PTLD occur with increased frequency in the first year following transplantation , with NHL having greater chances of occurrence in cardiothoracic transplant recipients. Male population especially younger group had more chances of cancer but BMI and dialysis have no effect. No increased risk of leukemias ,breast, uterine, ovarian, and prostate cancer are observed in post-transplant patients. Level of evidence
This is a retrospective cohort level of evidence II What are the drawbacks when we use the registry data?
No data available on immunosuppression protocol.
Comparison group was not properly selected.
No active follow up done
No validity and generalisabilty of the results.
Introduction:
An increased risk of developing cancer is an established complication associated with immunosuppression.
Numerous studies have investigated cancer incidents after transplantation.
Materials and methods:
This cohort study consists of all patients transplanted in England, Wales and Scotland.
The cancer registries code any new malignancy on the basis of available histology and other information.
All patients with cancer diagnosis within one month of transplant were excluded.
Statistical methods:
Cancer incidents incidence in transplant population was compared with general people in UK using standerdized incidence ratio
Registration of newly diagnosed cancers in England were obtained from office for national statistics.
Data on immunosuppression was obtained at 3 months following transplantation.
Results:
Of the 37617 transplanted patients, 25105 (67%) received a kidney transplant, 18% liver, 10% heart and 5% lung . The median follow up period was 16 years.
A total of about 5704 (15%) developed a cancer in this period.
NMSC is much more common with the standardized incidence was 14.4%.
The overall incidence rate of cancer in the transplanted population is just twice that of general population.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancers is much less in liver recipients and the SIR for cancer of the lip in this patients is less. Lymphoma rates are similar except that non Hodgkins lyphoma has a greater incidence in cardiothoracic transplant.
Kidney transplant recipients have increased incidence of malignancies, The study was done with the aim of evaluating the malignancy incidence in transplant recipients and compare the incidence following different organ transplants.
This was a retrospective study involving data from 10 cancer registries (8 from England and 1 each from Wales and Scotland) for a period of 28 years (1980 to 2007) was done. The cohort included 37,617 transplant recipients who received a first kidney, liver, heart, or lung transplant. Multiorgan transplant, pancreas transplant recipients and those with cancer diagnosed within 30 days of transplant (except post-transplant lymphoproliferative disease – PTLD) were excluded from the study. Cancer incidence in the cohort was compared with the general population of UK using the Standardized Incidence Ratio (SIR).
Results:
67% of the study population received a kidney transplant while liver, heart and lung transplant recipients comprised 18%, 10% and 5% of the study population respectively. Median follow-up was 16 years. 15% of the patients developed cancer during the study period. Cancer incidence rate was double in heart, kidney or liver transplant, and 3 times in lung or combined heart-lung transplant. Cancer incidence rate at 10 years post-transplant was more than double as compared to 10-year incidence rate of cancer in general population of England (9% versus 3.6%). The SIR were high for non-melanoma skin cancer (NMSC), Lip cancer and Kaposi sarcoma (16.6, 65.6, and 17.1 respectively).
SIR is greatest for lung transplant recipients. In liver transplant, the NMSC SIR is less and lip cancer SIR is also less than half of that in other transplants while oral cancer SIR is high at 10, especially in those with alcoholic liver disease. The SIR of non-Hodgkin’s Lymphoma (NHL) is high in cardiothoracic transplant. Pancreas, uterus and bladder cancer have constant SIRs.
Factors affecting time to cancer diagnosis include male gender and increased age. SIRs for each cancer decrease with increasing age. Incidence of NMSC in kidney transplant was not affected by use of tacrolimus or cyclosporine, or azathioprine or MMF use. NHL rates were higher in UK than in Sweden, Finland, or Canada.
Weaknesses: Lack of complete data on immunosuppression and likely underestimation of cancer incidence rates due to inclusion of first cancer occurrence only in the study.
Recommendations:Counselling and screening for NMSC, lip and anal cancer in all solid organ transplant recipients. Screen for aerodigestive tract, hepatocellular carcinoma (in cirrhosis), and colonoscopy in primary sclerosing cholangitis in liver transplant patients. For kidney transplant recipients, regular ultrasound for renal cell carcinoma in acquired cystic kidney disease, and cystoscopy for analgesic nephropathy or aristolochia related interstitial nephritis is recommended.
2. What is the level of evidence provided by this article?
Level of evidence: Level 2 – retrospective cohort study
3. What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
a) Variable quality of the data.
b) Participants lost to follow-up on long-term
c) Change in classification/ diagnostic parameters over time, leading to difficulty in standardizing the data at time of analysis.
d) Lack of control group
e) Bias associated with the data collection
f) Underestimation of the prevalence/ incidence rates due to underreporting
Introduction There is an increased frequency of newly diagnosed cancers after organ transplantation. It is crucial to recognize the increased risk and tell the patient before transplantation in order to formulate a rational strategy for screening and surveillance in the postoperative period. The objective of the study was to compare the incidence of newly diagnosed cancer to that of the general population. Additionally, the incidence of malignancy following transplants of solid organs was compared. Methodology From 1980 through 2007, all transplants of solid organs from the United Kingdom, Wales, and Scotland were included. Heart and lung transplants are classified as lung transplants, whereas pancreas and kidney transplants are classified as kidney transplants. Results · NMSC is the most prevalent complication after kidney transplant, occurring 14 times more frequently than in the matched UK general population. In all transplanted organs, the incidence of additional malignancies was two times that of the general population, and it was significantly greater in lung and heart transplant patients. Lower malignancy rates in liver transplant recipients may be attributable to the Uprotocol’s lack of induction treatment and lower immunosuppressive dosage. In the first year following transplantation, PTLD prevalence was higher, and non-lymphoma Hodgkin’s was more prevalent in cardiothoracic transplants. Other than NMSC and PTLD, the incidence of malignancies in recipients older than 50 is comparable to that of the general population. · Younger age at transplant and men are associated with an increased risk of cancer, however BMI and dialysis do not raise the risk of cancer. Leukemias and breast, uterine, ovarian, prostate, and pancreatic cancers occur with the same frequency in organ recipients as in the general population. Conclusion This study identifies patient groups and cancer types, contributes to the development of a surveillance program, and provides information for counseling pretransplant patients about the risk of cancer. All transplant patients should be checked routinely for NMSC, oral, and anal malignancies, in addition to adopting a sun-safe lifestyle. Regular renal ultrasound for kidney allografts and native kidneys for tumors is especially important for those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis, which also require cystoscopic evaluation. Level of evidence This is a retrospective cohort level of evidence II What are the drawbacks when we use the registry data? Voluntary reporting may underestimate the incidence rate. It may be obtained from different countries, which may bias it due to reference population decline.
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations of this study. yes, under-reporting may be an issue here.
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit
· Summarise the article
o Introduction
The increased risk of malignancy is a well-recognized complication among organ transplant recipients on immunosuppressive therapy.
o Study objectives
To describe the incidence of de novo malignancies in transplant recipients and to compare these incidences in different types of organ transplant.
o Methods
A retrospective cohort study of 37,617 transplanted patients who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007 in England, Wales and Scotland. Patients were followed up from the date of 1st transplant to date of 1st reported de novo malignancy, or date of death within the study period. Pancreas transplant recipients and other multi-organ transplant recipients (except heart-lung and pancreas-kidney) were excluded.
o Results
-Fifteen percent (5706 patients) developed cancer within the study period.
-NMSC was registered as the 1st cancer in 3276 patients; among these patients, 426 developed a different de novo cancer.
-A total of 2856 patients were noted to have a de novo cancer other than a NMSC.
-The 10-year incidence of de novo cancer was two times greater in transplant recipients compared to the general population.
-The overall incidence of cancer in transplant recipients was twice that of the general population.
-The incidence of NMSC was almost 14 times greater that of the general population.
-The incidence of different types of malignancy differs with the organ transplanted.
-NMSC, lip cancer, KS, PTLD and anal cancers had the highest SIRs.
-NMSC had an SIR of more than 16 times in kidney and cardiothoracic transplant recipients. This was 3 times higher than that of liver transplant recipients.
-Lung transplant recipients had the greatest overall SIR.
-In liver transplant recipients, incidence of NMSC was much less, so was the SIR for lip and anal cancer compared to other organ transplants; however, incidence of oral cancer was high.
-NHL has a greater incidence in cardiothoracic transplant recipients.
-Generally, the SIRs of each cancer decreased with increasing age and were higher in males than females.
-Initial immunosuppression therapy did not affect the incidence of NMSC in kidney transplant recipients.
-The incidence of KS and renal cell carcinoma has increased among kidney transplant recipients.
-Geographical location also had an impact on the incidence rates of many cancers.
-Smoking and underlying viral infections can increase risk of developing malignancies.
o Weakness
-Incomplete data on immunosuppressive therapy
-Underreporting of cases
-Censoring of recipients at the 1st occurrence of any malignancy (except NMSC)
-Different induction therapies for different organ transplants
o Conclusion
NMSC is the most common malignancy, hence all transplant recipients should be screened regularly for NMSC, including lip and anal cancer. Lifestyle changes to reduce sun exposure should be emphasized.
·What is the level of evidence provided by this article?
Level II – retrospective cohort study
·What are the drawbacks when we use the registry data?
-Lack of data verification
-Incomplete data
-Underreporting/ underestimation of cases
-Selection bias
-Variable quality of data
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
Transplantation is associated with immunosuppressive meds with antecedent increased risk of de novo malignancy post transplant. underscoring the above is the need for an appropriate follow up post transplant and improve our outcomes.
STUDY OBJECTIVE.
To establish the incidence rate of de novo malignancies in British Solid Organ Transplant Recipients in comparison to the general population.
METHODOLOGY.
-A retrospective cohort study on 37617 transplant recipient patients transplanted in Wales, England and Scotland between 1st january 1980 and 31st December 2017 and followed up from date of transplant to either 1st denovo malignancy or death during the study period.
-The cancer incidence rates post transplant were compared with those in the general population using Standard Incidence Ratio and appropriately adjusted for gender, time and age.
INCLUSION CRITERIA.
Pts transplanted in England ,Wales and Scotland ho got 1st kidney, liver, heart or lung transplant between 1st jan 1980 to 31st dc 2017.
-Pts with NHS number.
-15%[5706] of patients developed a denovo malignancy during the study period.
-Incidence of cancer in transplanted population is x2 that in the general population esp for NMSC, lip and KS.
-NMSC incidence is less in liver transplant recipients and the SIR for lip malignancies less than half compared to other organ transplant recipients.
-NHL has greater incidence in cardiothoracic organ recipients compared to other organ recipients. For all types of recipients, SIR for NHL increases in 1st year then declines while for the other types of malignancies they do have a varied pattern.
-Alcoholic liver disease is strongly linked to oral malignancies in liver transplant recipients.
-Males are more at risk for malignancies post transplant compared to females.
-The incidence of breast and uterine cancer were unaffected by transplantation in comparison to the general population.
-We did not get strong evidence that the the of immunosuppressive medication affected the incidence of NMSC in kidney transplant recipients.
STUDY LIMITATIONS.
-lack of enough data on immunosuppressive medication.
-Inaccurate incidences of skin malignancies due to underreporting possible from excision of some lesions before a histological diagnosis was made.
CONCLUSION.
-Age appropriate screening and follow up post transplant should be done. This cohort of patients should be counselled pre transplant about risk of malignancies post transplant especially NMSC, lip and anal cancer and the importance of screening .Alcoholics undergoing liver transplant should be screened for PSC nd have regular colonoscopies post transplant.
LEVEL OF EVIDENCE
2 – Retrospective cohort study.
DRAWBACK OF REGISTRY.
-No standard tool to ensure quality of results across the different studies.
-Missing data
-No uniformity in study designs of chosen RCTs.
o Denovo cancer in transplant patients is a well-known complication with greater morbidity and mortality.
o Skin cancer (melanoma and none melanoma), lip and ana cancer, PTLD are among most common types.
o The site of organ transplantation (lung, liver, kidney, etc…) is associated with variable incidence of cancer among transplant patients.
o The higher incidence of cancer among transplant patients is expressed as standardized incidence ratio (SIR) which represents the ratio between the observed and expected cancer cases.
o Increased incidence of cancer is related to cumulative effect of immunosuppression rather than being related to a particular drug.
o The cardiothoracic (lung with or without heart) transplant recipients have the highest incidence of none melanoma skin cancer due to use of aggressive immunosuppressive therapy (including induction therapy and TAC based triple immunosuppressive therapy).
o while liver transplantation has the lowest incidence (due to none-use of induction therapy and azathioprine in maintenance immunosuppressive therapy in liver transplantation.
o Lymphoma also is higher among lung transplant recipients.
o The incidence of cancer also varies between different locations that may be attributed to associated risk factors as ethnicity and personal variations as smoking and dietary habits.
o In addition, the original disease (reason for transplantation) may have a role:
§ Smoking which leads to lung damage and lung transplantation (it itself increases risk of lung cancer).
§ Sclerosing cholangitis requiring liver transplantation is associated with colitis and cancer colon.
§ Analgesic nephropathy requiring kidney transplantation and also it increases the risk of urothelial carcinoma.
o Among kidney transplant recipients, none melanoma skin cancer, Kaposi sarcoma, PTLD and renal cell carcinoma are increasing in incidence in last few years that may be attributed to aggressive immunosuppressive therapy (and use of suppressive anti-microbial therapy that prevent opportunistic infections and make our patients tolerating stronger immunosuppressants).
o Renal cell carcinoma may be related to acquired cystic kidney disease due to aging of the recipient (develop cancer in the aging native kidney).
o Screening and surveillance programs should consider the site of organ transplantation and the risky site screening as colonoscopy for cancer colon in case of sclerosing cholangitis, frequent cystoscopy for those transplanted for analgesic nephropathy and regular US for hepatocellular carcinoma in cirrhotic patients.
o Early detection and treatment of cancer improve the patient outcomes.
· Level of evidence: II (retrospective cohort study)
· Drawbacks of registry data:
o It depends on voluntary reporting of cancer so actually it underestimates the cancer incidence.
o Large proportion of missing data (none reported cases) as 17 % of UK transplant cases as in the current study.
o As regard skin cancer registration: many lesions are being excised with histological analysis and confirmation of malignancy plus missing data about basal cell carcinoma.
o Sometimes, incomplete data and lacking details that may be so important as type of immunosuppressive therapy used in each patient and site of origin of renal cell carcinoma either in the graft or the native kidney.
o Lack of documentation of associated risk factors as concomitant diseases or any personal habits that may increase the cancer risk.
o In case of 2nd cancer, only the 1st even is documented (that underestimates the cancer incidence).
Comparison of the incidence of malignancy in Recipients of different types 0f Organ: A UK Registry Audit: Introduction: The screening of post transplant cancer is as important as education of the recipients about the risk of developing cancer post transplant, inorder to understand the increasing risk and to plan measures to reduce this risk. This is UK registry is the first registry that study the risk of cancer in diffrent organ post transplantation Results:
Total number of recipients in the registry is 37, 617.
25, 104 (67%) receive a kidney or simultaneous kidney and pancrease transpnat. 18% liver, 10% a heart, and 5% a lung, or heart/lung.
The median follow up period was 16 years .
15% (5706) of recipients develop cancer during this time.
The first cancer develop was NMSC, in 3276 recipients.
426 recipients develop a different de novo cancer other than a NMSC.
The total number of de novo other than NMSC was more.
The 10 years incidence of cancer in solid transplant recipient was double the total number in the same matched group in the population, 90/1000, and 36/1000 respectively.
The incidence rate of NMSC is 14 times higher than the incidence rate in general population.
The overall incidence of cancer in the transplant recipient is twice the incidence rate in general population.
The overall SIR is more in the lung transplant.
Non-Hodgkins lymphoma is geater in cardiothoracic transplant.
The incidence rate is greater in male than female.
The incidence of occurrence doesnot affected by the types of immunosuppressant medication.
Discussion:
The incidence in cancer other than NMSC is twice as incidence in general population.
The estimate of incidence may be understimate as reporting inceidence was not complete, and not properly registered.
NMSC may have an underline viral infection association, and the reduced incidence may be occur with lower doses of maintenence immunosuppressants.
Cigrette smoking may cause a higher risk of inducing cancer than in general population.
Some cancer incidence may be related to old donors who alredy has an undiscovered underline tumor.
Weaknesses in this study:
Deficient completed data regarding immunosuppressants.
Different induction agent was used for different types of organ trasplants.
All occurrance of cancer were related to immunosuppressant, while viral infection had a higher risk of ccancer development.
Level of evdence: Cohort (II). Drawback when use a registry data:
Data taken from registeries, may not match the requiring data for such study.
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations and strengths of this study.What are strengths of this study?
Please summarise this article Introduction:
The risk of malignancy is increased in organ transplant population. Aim of the study:
-Evaluate the incidence of de novo malignancy in British SOT recipients of different organs
-Compare it with incidence rates in the general population.
Materials and Methods:
– Using data on all transplant recipients in the UK Transplant Registry, held by NHSBT, has been linked to information on cancer registrations following SOT recorded in England, Wales and Scotland.
– Study period: between 1 January 1980 and 31 December 2007.
– All patients with cancer diagnosis within one month of transplant were excluded, except for patients diagnosed with PTLD.
– Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
– Standardized Incidence Ratio SIR used to compare cancer incidence in the transplant population with matched general UK population.
Results
-The cohort consists of 37617 transplanted patients.
– The median follow up period was 16 years
– The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population.
– NMSC is more common over 14 times that of the general population.
– The SIR is high for NMSC, cancer of the lip, PTLD and anal cancer, but the incidence differs according to the organ transplanted.
– Patterns in SIR over time since transplantation are different for different types of transplant recipient,
as well as for different malignancies.
-The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
-The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Limitations:
– No sufficient data on immunosuppression.
– The cancer incidence rates in this study are underestimates, since the study has censored a recipient
at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
Implications:
– National screening program.
– Patients counseling.
What is the level of evidence provided by this article?
level 2 evidence; observational longitudinal cohort study with population data as controls.
What are the drawbacks when we use the registry data?
-The intended design does not automatically lead to a study of a certain quality.
-Variable quality of the collected data.
– No specific tool exists for assessing the quality of a registry-based study
– Need for external and internal validation of collected data
– Possible influence of confounders.
– Absent of complete data.
– Additional work for data collection.
– Lack of control group.
– Complete and long-term follow-up remains challenging (which may underestimate rates of adverse events).
– Non-homogeneous definition and scope of international registry items
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
Complication of organ transplantation and the associated immunosuppression is an increase risk of developing of de novo cancers .
Objectives :
Understanding the increased risk of denovo cancers in transplant patients
To allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods:
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number. Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients.
The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).
Results:
The 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years
A total of 5706 patients (15%) developed a cancer in this period.
In 3276 patients the first cancer registered following transplantation was a NMSC (C44), and of these 426 were subsequently registered as having developed a different de novo cancer.
The 2856 patients were registered with a de novo cancer other than a non melanoma skin cancer
Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients
This overall relative risk is more or less constant from two years after transplantation. NMSC is much more common, and the corresponding standardized incidence was 14.4 (95% confidence interval: 13.8–15.0), meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population
The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients
The incidence of non melanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients
For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines.
weakness of the study:
The lack of complete data on immunosuppression.
Conclusion :
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients
Level : 11 cohort study
Drawback:’
Disadvantage or inconvenience .the negative parts of situation
That is an excellent summary and very well structured reply. I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
-The study assessed the SIR of de novo malignancies after transplantation in Britain between 1984 and 2007.
-The overall incidence rate of cancer in the transplanted population is just over twice that of the general population.
-The overall incidence is much higher after lung transplantation compared to other oragn transplantation.
-Among kidney tx:- SIR of NMSC is 16.6 and 2.4 for other malignancies.
-The incidence of NMSC was not affected by the type of IS.
-The SIR for malignancies decreases with age and in patients aged
>50 y, tumors other than NMSC and PTLD is not much greater in
comparison to general population.
-The SIR of NHL increases to peak at 1-year post transplantation then decreases.
-The SIR for malignancies after kidney and hear TX quickly double the general population while after lung or liver TX increases dramatically in the first year then decreases dramatically.
-In general, HR of malignancies increases with age and in males after organ transplantation.
level of evidence: cohort study IIb
Limitation of the study:
1- A retrospective study with inherent selection bias
2- Heterogenecity of data, different sources(countries) and outcomes
3- lack of immunosuppression data.
4- The cancer incidence is underestimated, as it censored only first event. Thus, developing other cancers was not reported.
1- it is the first detailed registry study describing the cancer occurrence after SOT in UK
2- Data provided helps in designing a follow-up regimen for cancer surveillance after different types of SOT
Please summarise this article There is higher incidence of denovo cancer post organ transplantation. It is important to understand the increased risk and inform the patient before transplant so that a rational approach can be formed for screening and surveillance in the postoperative period. The purpose of the study was to compare the incidence of denovo cancer with incidence in general population. Also comparison was done on incidence of cancer following different solid organ transplants. Methodology All solid organ transplants were included from 1980 to 2007 from UK , Wales and Scotland. Combined heart and lung transplant- considered as lungs transplant , while pancreas and kidney transplant as kidney transplant. Results The cancer incidence was twice than general population after kidney , heart and liver transplants. It was three times higher in those having lung transplants. The incidence of NMSC was 13 times higher than general population. The incidence of breast cancer is not increased after kidney transplant. The most common malignancies after renal transplant are PTLD, NMSC, RCC , lip and anal cancers. The incidence of cervical cancer is the same as general population. The incidence of NMSC is 13 times higher . The incidence of lip and oral cancer is less following liver transplant. What is the level of evidence provided by this article? Cohort study level 11 What are the drawbacks when we use the registry data? Data from multiple sources and countries There can be selection bias Incomplete data Incomplete or loss to follow up Potential outcomes maybe lacking
Aim of the study: To evaluate the incidence of de-novo cancer in the general population and solid organ transplant recipients and to compare the incidence of de-novo cancers among different organ transplantation.
Methodology: This is a retrospective cohort study for all solid organ transplant recipients obtain data from cancer registries in England, Wales and Scotland. In this study standardized Incidence Ratios matched for age, gender and time period were used to compare de-novo malignancy in solid organ transplant recipients with general population.
Result: Among 37617 transplanted patients 67% kidney, 18% liver, 10% heart, and 5% of lung transplant. Median follow up was 16 years. 15% patients develop cancer in this time frame. 3276 patients got first time cancer and registered. The most common cancer is non-melanoma skin cancer and its incidence is higher than that of general population.
Conclusion: The study identify patient groups and cancer types, aids in surveillance programs, and provides information on warning transplant candidates about the possibility of cancer.
Level of evidence: Level II
Drawback of using registry data:
Data quality is variable and there is lack of follow-up.
Introduction:
Increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs. Materials and Methods:
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant, has been linked to information on cancer registrations following solid organ transplantation recorded by the eight cancer registries in England and the separate registries for Wales and Scotland. Results:
Of the 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC, and of these 426 were subsequently registered as having developed a different de novo cancer.
Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic.
The incidence of oral cancer in liver recipients is also high.
Following kidney transplantation, Standardized Incidence Ratios increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for others (Kaposi sarcoma, leukemia).
The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant. Factors affecting time to cancer diagnosis:
Male.
Age.
Primary disease affected the risk of skin cancer in liver transplant. Discussion:
recipients of a heart, kidney or liver, is over twice that of the general population and over three times higher in recipients of lung or combined heart and lung transplants .NMSC is the most common malignancy.
Study shows a very high incidence of post transplant lymphoma and Kaposi’s sarcoma.
E other cancer whose incidence is clearly increasing in renal transplant recipients over the study period is renal cell carcinoma. Limitation of the study:
The registries do not distinguish between cancers arising in the native kidneys or in the transplant, and it is possible that the increase in incidence also reflects the aging donor population who may have an unrecognized renal cancer.
A weakness of the study is the lack of complete data on immunosuppression.
It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded. 2. What is the level of evidence provided by this article?
Level of evidence 11. 1. What are the drawbacks when we use the registry data?
Additional work for data collection
– Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders
– Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission.
– Target population depends on external validity (participating healthcare special disciplines)
– Non-homogeneous definition and scope of international registry items
– Complex data privacy issues
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization
Please summarise this article: Introduction: The recipients of solid organ transplantation are at increased risk of de novo malignancies, that is proposed to be due to immunosuppressive medications. This mandates patients counseling and establishment of a screening and surveillance in the post-operative period. This retrospective cohort study conducted in Britain comparing the incidence of different types of cancer in the post-transplantation recipients to general population incidence of cancer, in comparable base line characteristics – age, sex, gender, …etc. Methods: Retrospective cohort of 37617 transplant patients having NHS number from first 1January; 1980 to 31December; 2007, of them 25104 received kidney and kidney pancreas transplant, 18% received liver transplant, 10% heart transplant, and 5% received lung/heart lung transplant. Exclusion crtiteria: – Pancreas alone transplantation. – Prevalent cancers at the time of transplantation. – Cancers within a month post transplantation(except 620 patients diagnosed with PTLD). – Multi-organ transplant recipients. Results: – NMSC is the commonest to occur after kidney transplant with 14 times more than the matched general UK population. – The incidence of other malignancies were 2 times higher the general population, in all different organ transplants, quit higher in lung heart transplant patients. – Lower incidence of malignancies noticed in liver transplant recipients, may be due to no induction therapy by the UK protocol, and lower immunosuppressive dosage used. – PTLD incidence was higher in the first year after transplantation, non Hudgkin’s lymphoma more in cardiothoracic transplants. – The incidence of cancers other than NMSC and PTLD in recipients aged > 50 is not much greater than that of the general population. – Younger the age at transplant and males are more at risk of having cancer, BMI and whether or not the patient was on dialysis does not increase the risk of cancer. – Breast, uterine, overian, prostate, pancreas cancers, and leukemias occurs in organ recipient at the same incidence with the general population. Limitations: – Lack of data on immunosuppression. – Heart transplant patients received ATG induction therapy, and higher CNI levels needed, while liver recipients received lower immunosuppression. – Underestimation of cancer incidence, as only the first cancer reported. Conclusion: – The study identify patient groups and cancer types, helps in surveillance program, and providing data on counselling pretransplant patients on the risk of malignancy. – All transplant patients should be screened regularly for NMSC, oral and anal cancers, combined with lifestyle changes prevents sun exposure. – Early detection of cancer in such patients does not translate to superior cure.
What is the level of evidence provided by this article? Level of evidence II – retrospective cohort has been exposed to a risk /outcome. What are the drawbacks when we use the registry data? – Insufficient data form the medical charts, and data description. – Absence of monitoring data, eg; different treatment protocols in different centers. – Lack of comparable control group.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone. That is a superb analysis. Ajay
De-novo cancer in solid-organ-transplant recipients has a double 10-year incidence compared to the general population.
Aim of the study:
1-To assess the incidence of de-novo cancer in solid organ transplant recipients compared to general population.
2-To compare the incidence of de-novo cancers among different organs transplantation.
Study Design and methods:
This is a retrospective cohort study for all solid organ transplant recipients in England, Wales and Scotland between 01/01/1980 and 31/12/2007.
Data were collected from NHSBT from 8 cancer registries in England and registries in Wales and Scotland.
SIRs (standardized Incidence Ratios matched for age, gender and time period) were used to compare de-novo malignancy in Tx recipients with general population.
Inclusion:
1-Recipients of first kidney, liver, pancreas, heart or lung transplant.
2-Recipients who had an NHS number.
3-Known age and gender at time of transplantation.
Study Population: Total number of cohort 37617 recipients.
67% kidney Tx recipients. 18% liver Tx recipients. 10% a heart and 5%a lung (or heart/lung)
Exclusion:
Recipients with cancer diagnosed within first month’s post Tx. 33 pancreas alone Tx, and 177 multi-organ Tx recipients.
Follow up: from date of first transplant to the earliest of the date of first reported de-novo cancer or date of death within the study period. Median follow up was 16 years.
Results:
1-De-novo cancer in solid-organ-transplant recipients has a double 10-year incidence compared to the general population.
2-NMSC is 13 times higher incidence in Tx recipients.
3-The de-novo cancer SIR in lung transplant recipients is 3.6 as in general population.
4-Low incidence of cancer in liver Tx recipients is attributed to lack of induction IS and low doses of maintenance IS.
5-The incidence of PTLD is higher in the UK compared to Canada, Australia and Sweden.
6-Solid organ transplantation doesn’t increase the risk of breast or cervical cancer.
Study Weakness:
1-Absent data about IS protocols.
2-Underestimation of cancer incidence because it collected data about first de-novo cancer, so second cancer will not be recorded.
Recommendations:
Pre-transplant counselling.
Regular screening for NMSC, lip, and anal cancer.
Regular pelvic-abdominal USS for renal TX recipients to rule out cancer in native or Tx kidneys.
Regular USS liver to rule out HCC development.
2. What is the level of evidence provided by this article?
Level II, retrospective cohort study.
3. What are the drawbacks when we use the registry data?
1-Absent proper control group
2-Data collected from different registries and centers.
3-Selection Bias because of different assessment, non-random sampling and treatment criteria especially using the international classification of diseases over the duration of the study depending on the decade of ICD and data collected.
4-Lack of complete data especially that related to immunosuppression protocols and life style.
5-Heterogenous data description.
6-Subclinical cases may not be registered.
7-Data monitoring and validation are questionable and variable.
8-Follow up data is lost and outcomes are missed leading to underestimation of the incidence.
9-Complex statistical data to reduce errors.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone. That is a superb analysis. Ajay
An established complication of organ transplant and the associated immunosuppression is malignancy and its incidence is increasing. The largest standardize ration is very high for the cancer of lip, skin and PTLD, and anal but the incidence of type of cancer are different according to organ transplant
National registry data have been reported that recipient of kidney transplant from different country including Canada,swedon,japan,finland,Australia and the USA. Also from others studies data from large multicentre registries.
Cohart study consist of all patient transplanted in England, Wale and Scotland who received their first organ transplant including kidney, liver, heart, and lung from 1980 to 2007
WHO ICD-1 code was arranged for any new malignancy on the basis of available histology.
RESULT
Recipient characteristic in th e study from 37617 transplanted patients 67% were kidney 18% liver 10% heart and 5% lung were transplanted. Median follow up was 16 years.
15% patients develop cancer in this time period.
In 3276 patients they got cancer first time and registered.
From cancer the most common cancer is nonmelonoma skin cancer and its incidence is higher than general population.
The incidence of oral cancer is higher in liver transplant patients.
To conclude this in general the incidence if cancer in patient who received heart, kidney and liver is double than the general population and triple in lung and combined heart-lung transplanted patients.
Nonmelonoma cancer is most common in kidney and cardiothoracic transplant patients which id three time higher than liver transplant patients.
The incidence of NMSC is underestimated because of early diagnosis issue the lesion may be ablated and treated without histology.
Primary sclerosing cholagitis require liver transplant but the but its association with colitis that may leads to colon cancer and rectum.
Next cancer that have high incidence in kidney is renal cell carcinoma but it’s unclear.
The registries don’t distinguish between cancer arising from native kidney or transplanted kidney but possible cause is aging donor population may have underlying some renal cancer before transplantation and they may manifest later on.
Incidence of cancer in transplanted patients are might be because of they are immune compromised as they are very prone to develop viral infection rather they are on immunosuppressive medicine
This study has level 2
Drawback of registry data is;
1. Registry data can be used for different purpose. Using an available data for additional purposes, one needs to be sure that all the important information required to address a specific research question was collected in a manner that is sufficient to answer the question.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone. That is a good summary and an interesting analysis. Please type headings and sub-headings in bold or in underline. Ajay
It is well known that immunosuppression following organ transplantation increases the likelihood of developing de novo cancer.
In addition to educating the patient before to transplantation, knowing the malignancies that are more likely to develop in these individuals and characterizing those cancers can help with screening and monitoring in the postoperative period.
Aim
Compare the prevalence of de novo cancer with that of the general population as well as the prevalence of de novo cancer following organ transplant.
Methods
The first liver, heart, lung, and kidney transplant recipients in the United Kingdom, Wales, and Scotland were included in the cohort research from January 1, 1980 to December 31, 2007.
37617 beneficiaries with NHS numbers are included.
A combination pancreas and kidney transplant is treated as a kidney transplant, while a combined heart and double lung transplant is treated as a lung transplant.
All patients of multiple organ transplants as well as pancreas-only recipients were not included in the research.
Transplant recipients of the heart, kidney, or liver were shown to have a twice-as-high incidence of cancer (apart from NMSC).
The risk of de novo cancer is three times higher in recipients of lung or lung and heart transplants than in the general population.
Compared to liver transplant recipients, NMSC incidence was greater in kidney and cardio-thoracic transplant recipients.
The UK liver transplant protocol’s lack of biological induction, avoidance of azathioprine, and low maintenance immunosuppressive dose can be used to explain why liver transplant recipients had a lower risk of cancer.
The incidence of several cancers in the UK was comparable to those in Canada, Australia, and Sweden.
However, the UK had a greater prevalence of PTLD.
Between 1980 and 1984, the prevalence of PTLD increased nine times, which may be related to the use of severe immunosuppression.
An increase in the prevalence of renal cell carcinoma in recipients of renal transplants without a known reason.
Breast and cervical cancer rates did not rise following solid organ transplants.
The Incidence Of Malignancy Is Increased After Solid Organ Transplantation. So, It Is Important To Identify The Risk Factors & Type Of Malignancy For Patient Education, Counseling And Screening.
The Aim Of The Study
To Study The Incidence Of Denovo Cancers In The Post-transplant Patient Recipient & Compare These Incidences Following The Transplantation Of Different Organs.
THE STUDY DESIGN
Retrospective Cohort Study Of 37617 Transplanted Patients
INCLUSION CRITERIA
All transplanted patients in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
EXCLUSION CRITERIA
Patients With Cancer Diagnosis Within One Month Of Transplant Were Excluded.
The Study METHOD
Data From UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales.
Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period.
RESULT
the 10-year Incidence Of De Novo Cancer In Transplant
Recipients Is Twice That Of The General Population, With The Incidence Of Non-Melanoma Skin Cancer Being 13 Times Greater.
Non-Melanoma Skin Cancer, Cancer Of The Lip, Post-transplant
Lymphoproliferative Disease And Anal Cancer Have The Largest Standardized Incidence Ratios, But The Incidence Of Different Types Of Malignancy Differs According To The Organ Transplanted.
patterns In Standardized Incidence Ratios Over Time Since Transplantation
Are Different For Different Types Of Transplant Recipient, As Well As ForDifferent Malignancies.
WEAKNESS OF THE STUDY
-The lack of complete data on immunosuppression.
-The cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
CONCLUSION
-The study suggest that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure following transplantation
-Regular ultrasound scans for kidney transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is also indicated.
-The national cancer screening program may be affected by the results of this study
What is the level of evidence provided by this article?
-This was Retrospective cohort level II, comparing incidence rates of cancer in general population versus solid organ transplant recipients.
What are the drawbacks when we use the registry data?
when we use the registry data we should considered;
– Absence of an appropriate comparison group, Non random sampling
– The validity and generalizability of the registry
– Immunosuppression protocols were different in this period
– Identification is by the International Classification of Diseases (8, 9, or 10 depending on the decade of the study
– Underreporting from lack follow up may occur => which may underestimate rates of adverse events, Measurement error, Missing data and Missing outcomes
– Unregistered associated diseases;
– Lifestyle with incomplete data (body mass index, medications in use, smoking history);
– Patients seen in diverse centers /countries
– Laboratory targets that they modified (fasting blood glucose, for example);
– Heterogenicity in data description;
– Complex statistical data in an attempt to minimize errors
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit. Introduction:
Malignancy post organ transplant is one of the most common long term complications which is mainly multifactorial, here is UK transplant registry on cancer following solid organ transplantation. Methods and Statistical methods.
NHS Blood and Transplant (NHSBT) collect data on transplant recipients (between 1 January 1980 and 31 December 2007 )in the UK Transplant Registry which was recorded by the eight cancer registries in England and the separate registries for Wales and Scotland and the cohort consists of 37 617 transplanted patients.
Standardized incidence ratios calculated by comparing the incidence rates in the transplanted population with the general population, using matched for age, gender and time period and calculated the cumulative incidence of different cancers. Results.
1-The 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5%a lung (or heart/lung) with median follow up period for this cohort of patients was 16 years and (15%) developed a cancer in this period mainly a NMSC and others registered as de novo cancer .
2-The overall incidence rate of cancer in the transplanted population is just over twice that of the general population
3-10- years after transplantation, recipients have an overall incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period and standardized incidence was 14.4 which means that a transplant recipient is over 14 times that of the general population.
4- The standardized incidence ratios are particularly high for non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma.
5- NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients. Weakness points:
1-The lack of complete data on immunosuppression.
2-Change of immunosuppression protocol between organs( some received monotherapy and others received ATG with CNI based triple therapy). What is the level of evidence provided by this article?
Level of evidence III (retrospective study). What are the drawbacks when we use the registry data?
1-Variable quality of the collected data.
2-Lack of active follow-up (which may underestimate rates of adverse events).
Introduction:
Post transplant denote malignancies is a well known complication of transplantation ( due to high doses of immunosuppression). Pre-transplant patient counciling about risk of malignancy development and need for post transplant screening and surveillance are crucial.
Aim of the study:
Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs.
Method:
Cohort study include all solid organ transplant recipients (first liver, heart, lung and kidney transplant) in UK, Wales and Scotland, from 1Jan 1980 to 31Dec 2007.
37617 recipients included who have NHS number.
Combined heart and double lung transplantation considered as lung transplant, combined pancreas and kidney transplantation deal with as kidney transplantation.
Pancreas alone & all other multi organ transplant recipients were excluded from the study.
Result & discussion:
Incidence of cancer (except NMSC) in heart, kidney, or liver transplant recipient found to be twice higher than general population.
In lung or combined lung heart transplant recipients the risk of de novo malignancy 3 times higher than general population.
NMSC incidence was higher in kidney and cardio-thoracic transplant recipient than liver transplant recipients.
Lower incidence of cancer in liver transplant recipients can be explained by low dose of maintenance immunosuppression, avoidance of azathioprine, and absence of biological induction in UK liver transplant protocol.
Incidence of some malignancies in UK was similar to Canada, Australia & Sweden. But incidence of PTLD was higher in UK.
Incidence of PTLD increased 9 fold between 1980-1984 & this may be result of using aggressive immunosuppression .
Increase incidence of renal cell carcinoma in renal transplant recipient without clear cause.
Incidence of breast and cervical cancer not increased after solid organ transplantation.
Weakness of the study:
Lack of complete data of immunosuppression
Heart transplant recipients receive ATG as induction and higher level of CNI than other organ transplant recipients
Liver transplant recipients receive lower dose of immunosuppression under-estimation of cancer incidence.
level of evidence is 2
Drawback of registry data:
variable quality of data.
absence of active follow-up which may lead to under-estimation of adverse events.
Malignancy occur in a higher frequency in transplant recipients when compared to general population
This is mainly because of the immunosuppression, other important factor includes associated premalignant conditions that predispose to organ failure such as smoking as a cause of lung failure may cause other types of cancers, PSC as a cause of liver failure (which may be associated with colon cancer)
The current study is addressing the incidence of denovo solid organ malignancy in different organ transplantation using data registry from Britain including 37 617 transplanted patients in comparison to general population matched in age and sex
The results
The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants
The incidence of NMSC is 13 times that of general population
The incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of biological induction and avoidance of azathioprine in maintenance immunosuppression
The most common malignancies occurring in renal transplant recipients in the current study are NMSC, PTLD, lip and anal cancer and RCC, on the other hand the incidence of breast cancer is not increased due to unclear reason and the incidence of cervical cancer also is not higher which may be explained by active surveillance programs.
Conclusion
Malignancy occurring more frequently in organ transplantation, the frequency differ according to the type of transplant and site of cancer.
What is the level of evidence provided by this article?
This is a retrospective cohort level of evidence III
What are the drawbacks when we use the registry data?
It depends on voluntary reporting so may underestimate the incidence rate
It may be collected from several countries which may be associated with bias due to loss of reference population
Malignancy occur in a higher frequency in transplant recipients when compared to general population
This is mainly because of the immunosuppression, other important factor includes associated premalignant conditions that predispose to organ failure such as smoking as a cause of lung failure may cause other types of cancers, PSC as a cause of liver failure (which may be associated with colon cancer)
The current study is addressing the incidence of denovo solid organ malignancy in different organ transplantation using data registry from Britain including 37 617 transplanted patients in comparison to general population matched in age and sex The results
The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants
The incidence of NMSC is 13 times that of general population
The incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of biological induction and avoidance of azathioprine in maintenance immunosuppression
The most common malignancies occurring in renal transplant recipients in the current study are NMSC, PTLD, lip and anal cancer and RCC, on the other hand the incidence of breast cancer is not increased due to unclear reason and the incidence of cervical cancer also is not higher which may be explained by active surveillance programs. Conclusion
Malignancy occurring more frequently in organ transplantation, the frequency differ according to the type of transplant and site of cancer. What is the level of evidence provided by this article?
This is a retrospective cohort level of evidence II What are the drawbacks when we use the registry data?
It depends on voluntary reporting so may underestimate the incidence rate
It may be collected from several countries which may be associated with bias due to loss of reference population
THE AIM OF THE STUDY:
—————————————————————
Is to study the incidence of denovo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs.
THE STUDY DESIGN :
——————————————————-
Retrospective cohort study .
THE POPULATION;
——————————————————–
The cohort consists of 37617 transplanted patients.
THE INCLUSION CRITERIA :
————————————————————-
All transplanted patients in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
THE EXCLUSION CRITERIA;
———————————————————
1- Patients with cancer diagnosis within one month of transplant were excluded.
THE METHOD;
————————————————————
Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland
and Wales. Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period.
THE RESULT ;
————————————————————————-
1-The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of non melanoma skin cancer being 13 times greater.
2-Non melanoma skin cancer, cancer of the lip, post-transplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted.
3-Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies.
THE WEAKNESS OF THE STUDY;
——————————————————–
1-The lack of complete data on immunosuppression.
2-The cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
CONCLUSION;
—————————————————————–
1-The study identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pre transplant patients on the risk of malignancy.
2-following transplantation ,the study suggest that all transplant recipients should
be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure .
3- Patients undergoing liver transplant for alcohol should have regular surveillance of the aero digestive tract, and those with a diagnosis of primary sclerosing cholangitis who have their colon and rectum in situ should undergo regular colonoscopy.
4-The presence of recurrent graft cirrhosis should also be a cue to regular ultrasound surveillance for hepatocellular carcinoma.
5-Similarly a case can be made for subjecting renal transplant recipients to regular
ultrasound scans of their transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is also indicated.
What is the level of evidence provided by this article?
——————————————————————————
LEVEL III
What are the drawbacks when we use the registry data?
—————————————————————————————
1-Variable quality of the collected data.
2-Lack of active follow-up (which may underestimate rates of adverse events).
3-NO specific tool exists for assessing the quality of a registry-based study.
4- Absence of an appropriate comparison group.
5- The validity and generalizability of the registry .
Why do you think that this article provides level 3 evidence? However, that is an excellent summary and very well structured reply, dear Dr Abdelrehman. Ajay
This study is a historical cohort (level 2 of evidence) with patients who received their first organ donated between January 1980 and December 2007, crossing information from the British Transplant Registry with oncological records using the international code of diseases in England, Scotland, and Wales. The control group was selected from the general population with similar characteristics. Pancreas and multivisceral transplants were excluded. Patients diagnosed with cancer within the first thirty days after transplantation were also excluded, except for 620 patients who developed PTLD. The total number of patients included in the study was 37,617.
The analysis spanned 15 years after transplantation and was separated by type of transplant and cancer involved. Transplanted organ, age, sex, primary disease, smoking history, obesity (BMI greater than 30), dialysis at the time of transplantation, and the year in which it was performed was considered. Some data limitations such as BMI, immunosuppressant dose, and smoking history limited the statistical index.
Of these transplants, 25,104 (67%) were kidney, 18% liver, 10% heart, and 5% lung. A total of 5,706 patients (15%) developed cancer during this period. Ten years after transplantation, the risk of developing cancer is twice that of the general population, but specific cancers were more frequent. Non-melanoma skin cancers are more common with a 14.4% higher risk; in non-melanoma skin kidney transplantation it was 16.6; lips 65.6; Hodgkin’s Lymphoma 7.4; Non-Hodgkin lymphoma 12.5; breast 1.0; oral cavity 4.2; colorectal 1.8; anus 10; liver 2.4; lung 1.4; Kaposi’s sarcoma 17.1; kidney 7.9 and multiple myeloma 3.3.
Male sex and advanced age are risk factors. The type of transplant as well as the type of cancer are variable and present different data. Non-melanoma skin cancer is three times more frequent in kidney, heart, and lung transplantation when compared to liver transplantation. Some environmental situations (smoking load and exposure to oncogenic viruses) increase the risk for specific neoplasms.
Breast and prostate cancer do not seem to be related to an increase in frequency in transplant patients. A weakness of the study is the lack of data on immunosuppression and objective lifestyle data.
This study suggests an active and passive search for the investigation of non-melanoma skin cancer, without the need for additional investigation for breast and prostate cancer. The need for screening to investigate neoplasia due to potential oncogenic viruses is debatable and should be individualized and discussed with the patient by a multidisciplinary team.
Drawbacks
Some facts should be considered in registry studies:
1. Immunosuppression protocols were different in this period;
2. Identification is by the International Classification of Diseases (8, 9, or 10 depending on the decade of the study);
3. Underreporting may occur;
4. Unregistered associated diseases;
5. Lifestyle with incomplete data (body mass index, medications in use, smoking history);
6. Laboratory targets that they modified (fasting blood glucose, for example);
7. Heterogenicity in data description;
8. Complex statistical data in an attempt to minimize errors
-Immunosuppression and organ transplantation raise cancer risks.
-In this British study on cancer incidence in solid organ transplant recipients, we assess the incidence of de novo malignancies in allograft recipients after organ transplantation. The UK Transplant Registry has data from cancer registries in England, Scotland, and Wales. This data came from NHSBT.
To compare transplanted and general population incidence rates, age, gender, and time were used to find standardized incidence ratios that were the same for both groups.
Transplant recipients had a 10-year risk of de novo cancer that was doubled, and nonmelanoma skin cancer was 13 times higher.
The highest standardized incidence ratios are for non-melanoma skin cancer, lip cancer, post-transplant lymphoproliferative illness, and anal cancer. Malignancies vary with organ transplants. Standardized incidence ratios vary by transplant recipient type and malignancy. These findings affect nationwide screening programs.
-Cancer incidence is about twice as high in transplanted people.
-Nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma have high SIRs.
-Lung transplants had the highest SIR.
-Liver transplant recipients had lower rates of nonmelanoma skin cancer and lip cancer.
-Non-lymphoma Hodgkin’s is more common among cardiothoracic transplant patients. —Oral cancer is common among liver recipients, although 15 of 18 cases were in patients with alcoholic liver disease.
-As predicted, posttransplant lymphoma and Kaposi’s sarcoma had the highest incidence of all malignancies except NMSC.
-This research censored recipients at the first occurrence of any cancer (excluding NMSC), thus if they acquired a second cancer, it would not be reported. This may have underestimated cancer incidence rates.
-Breast cancer is one kind of cancer whose prevalence was not raised in our research and may perhaps be decreasing.
-Some transplanted illnesses are linked to other cancers or toxic exposure. Smoking may cause lung and heart transplants (emphysema and ischemic cardiomyopathy), as well as various cancers.
-NMSC incidence in kidney transplant patients was unchanged by three-month azathioprine, MMF, tacrolimus, or ciclosporin treatment. Other cancers have inadequate data for estimations.
Limitation:
A weakness of the study is the lack of complete data on immunosuppression.
What is the level of evidence provided by this article?
Retrospective cohort study, level of evidence 3
What are the drawbacks when we use the registry data?
-Additional work for data collection
– Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders – Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission
– Target population depends on external validity (participating healthcare special disciplines)
– Non-homogeneous definition and scope of international registry items
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomisation.
Hi Dr Nazer, Why do you think that this article provides level 3 evidence? This study would have inherent limitations as for any secondary data. I like your list of limitations of this study. Ajay
Please summarise this article
This is the first study to calculate standardized incidence ratios (SIRs) of de novo cancers in solid organ transplant recipients from 1980 to 2007 UK national registry data.
Results: 1.Overall cancers in solid organ transplant patients:
Incidence of cancer in transplanted patients is twice than general population
Non melanoma skin cancer(NMSC)(SIR 14.4), cancer of lip and Kaposi sarcoma incidences are particularly high
Overall SIRs is highest for lung/cardiothoracic transplants
SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
Impact of initial immunosuppression can’t be stated as lack of complete data
2.Cancers in relation to kidney transplant recipients:
Overall SIR of cancer:2.4
Most common cancer-NMSC(SIR 16)
Higher risk of NMSC, Lip, Hodgkin’s and non-Hodgkin’s lymphoma, oral cavity, anal, Kaposi sarcoma and kidney cancer compared to general population
3.Cancers in relation to liver transplant recipients:
Overall SIR of cancer: 2.2
Risk of lip, anal canal, NMSC is particularly lower compared to kidney transplant recipients due to absence of biological induction agents and lower maintenance immunosuppression in UK liver transplant protocols
4.Cancers in relation to lung or combined lung and heart transplantation:
Overall SIR:3.6
Higher incidence of cancer may be related to increase usage of immunosuppression(induction as well as maintenance)
5.Cancers in relation to heart transplant recipients :Overall SIR:2.5
What is the level of evidence provided by this article?
Level 3 (Retrospective, case-control, non-experimental observational study comparing incidence rates of cancer in general population versus solid organ transplant recipients)
What are the drawbacks when we use the registry data?
The following are some disadvantages or biases associated with registry data (1, 2, 3). A. Selection Bias
Inclusion/exclusion bias
Non Random sampling
Subclinical cases may not be captured
Secular trends in disease occurrence may change as availability of more sensitive test(like CT scan) with time
Lead time bias: increased number of cases and younger age at diagnosis with availability of newly introduced diagnostic test
Non response and study drop out
Differential participation bias: Lower participation likely by minority and lower socioeconomic groups
B. Information bias:
Measurement error
Missing data
Recall bias
Interviewer/observer bias
Reporting bias
C. Confounding bias, occurs either by group or indication:when measured or unmeasured factors that affect the outcome of interest are unevenly distributed among study arms.
D. Other bias:
Ecological bias/fallacy: resulting from the use of population-level data to draw inferences about individuals
Publication bias: negative studies/observations are less reported
References:
Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol. 2008;15(2):415-23.
Rubinger L, Ekhtiari S, Gazendam A, Bhandari M. Registries: Big data, bigger problems? Injury. 2021. DOI: 10.1016/j.injury.2021.12.016
Psoter KJ, Rosenfeld M. Opportunities and pitfalls of registry data for clinical research. Paediatr Respir Rev. 2013;14(3):141-5.
This study analyzed the transplant cohort and the standardized incidence ratio calculated from the registry data shows that the transplant cohort had more cancers compared to the general population. The general population used for the calculation/inference can be viewed as a “quasi-control group”
1- Summary
Introduction
Denovo cancer risk is high in organ transplant recipients and as immunosuppression complication.
Shedding light on the importance of explaining the risk to patients pretransplant and screening posttransplant.
This is the first British study on de novo malignancy comparing it’s incidence in organ transplant recipients versus in the general population .
Methods
This cohort study included all kidney ,liver,lung and heart transplant recipients with NHS number in England ,Wales and Scotland within 27 years.
The study included 37 617 transplanted patients followed from the first
transplant time till the first reported de novo malignancy or death within the study period.
Standardised incidence ratio was used to assess cancer incidence
Results
67% of the cases received a kidney transplant ,18% liver, 10% heart and 5% lung transplants within median follow up period of 16 years.
2856 patients were registered with a de novo cancer excluding nonmelanoma skin cancer.
The incidence rate of cancer for transplant recipients in 10 years after transplantation is more than double the incidence rate in the general population. The risk of NMSC occurrence is 14 times more in transplant recipients than in general population.
The overall incidence rate of cancer in the transplant recipients is more than twice that of the general population specially for NMSC, cancer of the lip and Kaposi sarcoma.
Lung transplant recipients had highest SIR.
Liver recipients had lowest incidence of NMSC and lowest SIR for lip cancer, and high incidence of oral cancers particularly with alcoholic liver disease.
Non Hodgkin lymphoma was highly associated with cardiothoracic transplant recipients .
SIR is high at the beginning of transplantation period and decreases with time but malignancy pattern varies between organs .
For kidney transplantation, SIR increases for NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach cancer and decreases for Kaposi sarcoma, leukaemia. SIRs for liver and ovarian cancer is high and decreases with time and that for breast, pancreas and uterine cancer is stationary.
SIRs for each cancer is inversely proportion to age .
Factors affecting time to cancer diagnosis showed high risk in male and increased with age .
The age and primary disease affected the risk of skin and colon cancer development in liver recipients .
PTLD risk is affected by gender and lung cancer risk depended on age group.
NMSC risk in kidney transplant recipients was unaffected by azathioprine , MMF ,tacrolimus or ciclosporin use.
Discussion
Cancer incidence in heart ,kidney and liver is more than double the incidence in general population and more than 3 times that of lung transplantation or combined cardiothoracic transplantation.
The most common malignancy is NSMC meanwhile their incidence could be underestimated due to lack of data .
Lip and anal canal cancers had low incidence in liver recipients.
NMSC is associated with viral infection and lower association with use of lower immunosuppressive doses.
The incidence rate of cancers in UK was similar to Australia , Canada and Sweden but there were some variations as UK had higher incidence of non Hodgkin lymphoma while Canada and Australia showed higher kidney cancer incidence.
Some diseases necessitating transplantation can be an indicator of exposure to a specific carcinogen .
Posttransplant lymphoma incidence in kidney recipients increased nearly 9 times within 4 years period due to the advances in immunosuppressives and antimicrobials.
Renal cell carcinoma incidence is increased in renal transplant recipients due to older recipients’ age and it’s association with acquired cystic kidney disease.
Data did not clarify if cancer originated from native or transplanted kidneys .
Breast cancer had low incidence in this study.
Cervical cancer screening programme with early detection and treatment in UK justify the low incidence of cancer cervix.
Limitations of this study include absence of data on immunosuppressives used, underestimating cancer risk.
This study advices for regular screening for NMSC along with lifestyle changing and lower sun exposure, primary sclerosing cholangitis cases need to undergo regular colonoscopy,liver cirrhosis cases need regular screening for HCC also renal transplant recipients require regular US screening for cancer of graft or native kidney.
Early identification of cancer in immunosuppressed cases does not guarantee high cur rate .
2- Level of evidence is 3
3- Drawbacks of using registry data include possible changes in the long term ,cofounders possible influence, validation of collected data is needed ,different local conditions in data collection and submission, Non homogeneity ,data privacy issues , long-term follow-up is difficult.
Introduction; the incidence of malignancy is increased after solid organ transplantation. Therefore it is important to identify the risk factors and the type of malignancy for patient education, counseling and screening.
Objective; to estimate the incident of de novo cancers in the post-transplant patient and compare these incidences after transplantation of different organs.
Methodology; combined data from UK transplant registry and data from cancer registries in England,Scotland and Wales were obtained by the utilization of NHS number. this was cohort study of 37617 recipients with follow up to the point of development of de novo malignancy or date of death within the study period. Incidence in the transplant recipients were compared to the general population by means of standardized incidence ratios (SIR)= the ratio of observed number of cancer cases to the expected number of cases, matched for age,gender and time period.
Results; 10 year incidence of de novo malignancy post-transplant is two times more than the general population and non-melanoma skin malignancy is 13 fold higher. Malignancies with highest SIR was non-melanoma skin cancer, cancer of the lip, PTLD and anal cancer.
Conclusions; the national cancer screening progam may be affected by the results of this study.
This was cohort study, level II
Drawbacks of the registry data;
1.Patients seen in diverse centers/countries
2.Assessment or treatment criteria may not be uniform i.e potential for selection bias
3.Incomplete data registration (weakness of the above study)
4.Loss of follow up data
5.Missing outcomes
The incidence of de novo malignancy post-transplant is higher than general population because of immunosuppression medications , and the incidence of specific malignancy differ from solid organ to another as documented by British registry in Britain.
In heart, liver and kidney post-transplant, the incidence of overall malignancy with the exclusion of non-melanoma skin cancer NMSC is 2- fold increase than general population (SIR 2.5, 2.2, 2.4) and more than 3-fold increase in lung and combined heart and lung transplant recipient (SIR 3.6).
SIR is standardized incidence ratio, which is the relation between number of observed cases and number of expected cases.
SIR of NMSC post kidney and cardiothoracic transplant is 16, this is 3 fold increase than post liver transplant.
The incidence of cancer may be under-estimated because of removal or ablation of the skin lesions without biopsy and histological examination.
Also the incidence depends on registration which differs from country to country and it is affected by many factors.
Denovo cancer is an important complication of organ transplantation.
Knowing about cancer is important for pretransplant counseling and posttransplant screening .
Aim of study: reported denovo malignancy in British solid organ transplant recipients and Compared it with the incidence rates in the general population and compared these incidences following the transplantation of different organs.
Material and methods
The cohort consist of 37617 patients( all patients transplanted in England,Wales and Scotland, who received a first kidney, liver , heart or lung transplant between 1 Jan 1980 and 31 Dec 2007, and who had an NHS number) with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported denovo malignancy or date of death within the study period.
Results
The registery study has shown evidence of different patterns of cancer occurrence in recipients of different organ type. The overall incidence of cancer ( excluding NMSC) in recipients of a heart, kidney or liver is over twice that of general population and over three times higher in recipients of lung or combined lung and heart transplants.
NMSC is the most common malignancy with a standardized incidence ratio of over than 16 for kidney and cardiothoracic transplant patients, which is three higher than that for liver transplants.
Level of evidence II
What are the drawbacks of registery data
Incomplete data registration, missing outcomes and loss of follow-up data
1. Please summarize this article
Introduction
It is known that cancer risk increased after organ transplantation.
Knowing the exact incidence of individual organ and comparison of different organs risk will influence counselling of patient pre transplantation and monitoring and screening post transplantation.
This is the first national registry data that compared denovo cancer incidence in organ transplantation with that of general population.
Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), has been linked to information on cancer registrations following solid organ transplantation recorded by the eight cancer registries in England and the separate registries for Wales and Scotland, using the NHS number. This number was not available for 17% of all transplant recipients since 1980, mainly those in the 1980s.
Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.
Result
Of the 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung). The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years). A total of 5706 patients (15%) developed a cancer in this period.
Ten years after transplan[1]tation, recipients have an overall incidence rate of 90 per Figure 1: Overall cumulative incidence of any de novo cancer (excluding nonmelanoma skin cancer) in the transplanted and general populations. thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period. This overall relative risk is more or less constant from two years after transplantation. NMSC is much more common, and the corresponding standardized incidence was 14.4 (95% confidence interval: 13.8–15.0), meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these pa[1]tients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
2. What is the level of evidence provided by this article?
11
3. What are the drawbacks when we use the registry data?
Uncertainty of accuracy.
Loss of a lot of data
Retrospective nature.
Rely on how accuracy is the data and its collection.
Introduction
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number. Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients. The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR) (9). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.All calculations were carried out using Statistical Analysis Software (SAS Institute, Cary). Computation of the incidence functions and the person years at risk was based on SAS macros
Results
Of the 37617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung). The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).A total of 5706 patients (15%) developed a cancer in this period. The overall incidence of cancer (excludingNMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
Conclusion-
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies. These results have implications for a national screening program.
What is the level of evidence provided by this article?
Level 2
What are the drawbacks when we use the registry data?
A weakness of the study is the lack of complete data on immunosuppression
· This observational longitudinal cohort study compared the incidence of de novo malignancy in SOT recipients with general population using the Standardized Incidence Ratio (SIR).
· It included all UK transplant patients from the (NHSBT data) from 1980 to 2007
· However, it excluded patients with diagnosis of cancer within one month post-transplant and PTLD.
· Results:
· The median follow up period of this study was 16 years(range: 8–26 years)
· The 10-year incidence of de novo malignancy in post-transplant patients was double that of general population. Also, non-melanoma skin cancer being the commonest(13 times greater than the general population).
· Other common cancers were cancer of the lip, Kaposi sarcoma, PTLD, anal cancer and kidney cancer.
Level of evidence:
· Level 2
What are the drawbacks when we use the registry data?
· Limited amount of data from the data registry
· Selection bias.
· Lack of follow-up
Introduction
The elevated risk of developing de novo malignancies is documented complication of solid organ transplantation as well as immunosuppression. Proper identification of risk factors presents to better rational approach to screening and surveillance later on. However this is the first unique work performed concerned by the study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
The study cohort involves all patients transplanted in England, Wales and Scotland, who received kidney, liver, heart, lung transplant, combined pancreas and kidney transplant or combined heart and double lung transplant between 1 January 1980 and 31 December 2007.
Those who underwent pancreas transplant alone were excluded, together with all other multi-organ transplant recipients. Also it was important to exclude cancers that may have been prevalent at the time of transplantation, so all patients with cancer diagnosis within one month of transplant were excluded except for the 620 patients diagnosed with post-transplant lymphoproliferative disease (PTLD).
The cohort consists of 37 617 transplanted patients with documented age and gender at transplantation. Study period covered the followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death.
Statistical methods
The Standardized Incidence Ratio (SIR) is the main point used to compare the cancer incidence in the transplant population to the general UK population. It relies on the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.
Data such as the expected number of incident cases was obtained by calculating the person years at risk of malignancy in the transplant population in five year age groups for each gender in each year between 1980 and 2007 was applied in the study.
Confidence intervals for these estimates and p-values for testing the hypothesis that the SIR is 1.0 were evaluated. It is worthy to mention that this analysis extended to 15 years following transplantation, and was carried out for each organ and all the different cancers.
For each organ type, the estimated cancer incidence on recipient age group and gender, primary disease, smoking history, obesity, dialytic status at the time of registration and transplant year [1980–1984, 1985–1989,1990–1994, 1995–1999, 2000–2004, 2005–2007] was modeled. One drawback of the study is the availability of smoking history which was absent in 70% in kidney recipients as well as obesity and immunosuppression.
The calculations were performed by using Statistical Analysis Software (SAS).
Results
A total of 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5%a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC (C44), and of these 426 were subsequently registered as having developed a different de novo cancer. The other 2856 patients were registered with a de novo cancer other than a non-melanoma skin cancer.
Ten years post transplantation, recipients have an incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
This estimated relative risk is nearly constant from two years post transplantation. NMSC is by far more prevalent with SIR was 14.4 (95% confidence interval: 13.8–15.0), which is best explained by the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The standardized incidence ratios are particularly high for non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients. The incidence of non-melanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients.
Concerning Lymphoma rates which are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was particularly alcoholic liver disease.
The incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. Interestingly, the SIR following lung transplantation increases dramatically at first and then declines over time.
The pattern is similar for liver recipients, although the SIR is generally lower.
Notably the SIR for non-Hodgkin’s lymphoma increases for all organs to a maximum at one year after transplantation and then declines. Post renal transplantation, the SIR increases for some cancers as NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach while decreases for others as Kaposi sarcoma, leukaemia.
The SIRs for liver and ovarian cancer increase in the years immediately post transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Concerning post liver transplantation, the SIR for several cancers as cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas peaks within 2 years of transplantation, and then declines steadily.
For post heart transplant recipients, the SIR for bladder, lung and oral cancer and Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
The pattern is similar following lung transplantation, except there is lack of evidence for the increase over time in the SIR for leukaemia and lung cancer.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
Fortunately, the incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Body mass index, and dialytic status at time of listing for transplantation did not significantly affect the hazard of cancer evident by these p values (p = 0.75 and 0.54, respectively).
For liver recipients, the recipient age group and primary disease affected the risk of skin cancer (p < 0.001 and 0.01, respectively) and colorectal cancer (p = 0.06 and 0.002, respectively).
Also it was shown that the risk of PTLD only depended on recipient gender (p = 0.02), and the risk of lung cancer depended only on recipient age group (p = 0.02). For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients (p = 0.004).
Regarding the impact of initial immunosuppression from the presented data only in renal transplant recipients the incidence of NMSC was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin.
Discussion
The overall incidence of cancer (except for NMSC), in recipients of a heart, kidney or liver, is exceeding double that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSC is still the most encountered malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
Liver recipients astonishingly appear to be relatively protected against cancer of the lip and anal canal, diseases which, like NMSC, have an underlying viral association and the lower rise in incidence for which may reflect lower doses of maintenance immunosuppression especially avoidance of azathioprine as well as the absence of biological induction agents in liver transplant immunosuppressive protocols.
Cigarette smoking for instance may be a contributing factor for the need of lung transplantation (emphysema) or heart transplantation (ischaemic cardiomyopathy).
Primary sclerosing cholangitis may require liver transplantation, but is also associated with colitis which might explain the increase in incidence of cancer of the colon and rectum; like alcohol (and the exposure to cigarette smoking which accompanies it) may account for the higher risk of oral cancer in liver recipients. Analgesic nephropathy or aristolochia use may necessitate renal transplantation, are also themselves risk factors for development of transitional cell carcinoma of the native urothelium.
The study again highlights the very high incidence of post-transplant lymphoma and Kaposi’s sarcoma. The incidence of post-transplant lymphoma in renal transplant recipients has increased ninefold since 1980–1984, an observation linked to the more aggressive immunosuppressive protocols being used.
It was also found that the incidence of breast cancer was twice that of the normal population. Other tumours as cervical carcinoma was known to have higher incidence as it is a consequence of papilloma virus infection but this has been overcome by the active cervical screening program in which the disease is being detected and treated before it even becomes invasive.
The importance highlighted on increased cancer risk is that clinicians during regular follow up are now aware of as well as this reflects the role of intense immunosuppression rather than being attributed to any particular drugs, since patients get immunosuppressed as a complication of human immunodeficiency virus infection have a similar pattern of increased cancer incidence.
The significance of studies such as ours is to identify patient groups, cancer types, which should form part of a cancer surveillance program, as well as to provide data for proper counselling pretransplant patients on the risk of malignancy.
The suggested recommendations for the time following transplantation for all transplant recipients is to screen for NMSC, including lip and anal cancer on regular basis being combined with lifestyle changes to reduce sun exposure. The need for any additional breast or cervical cancer screening wasn’t proved to be of value in such population.
Regarding liver transplant recipient it is advised that alcoholics should have regular surveillance of the aerodigestive tract. Also it is necessary for recipients suffering from primary sclerosing cholangitis disease to undergo regular colonoscopy.
The presence of recurrent graft cirrhosis mandates to regular ultrasound surveillance for hepatocellular carcinoma.
Other recommendations advocate regular ultrasound scans of renal transplant recipients to their transplant and native kidneys for evidence of tumor, particularly those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is further indicated.
Level Of evidence: II
The drawbacks when we use the registry data are mainly lack of complete information concerning obesity, smoking, immunosuppression protocols, and different induction protocols with different transplanted organs, unreported malignancies are also missed in both general and transplant population as well as variations among different countries.
Introduction
de novo cancer development is an established complication of organ transplantation.
Understanding the increased risk of cancers and the most common cancer types will help to clearly inform the patient before transplantation and allow a rational approach to screening and surveillance in the postoperative period.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
other studies investigated cancer incidence in recipients of a kidney, liver or cardiothoracic organ, with a focus on a single transplant type, a specific form of malignancy, experience at a single center, or a limited duration of follow-up.
Some other registries rely on voluntary reporting, leading to the underestimation of cancer incidence following transplantation.
Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), was linked to information on cancer registrations following SOT recorded by 8 cancer registries in England and in Wales and Scotland.
It included all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
The registry included 37 617 transplanted patients, they were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Cancer Registries code any new malignancy on the basis of available histology and other relevant information.
all patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD).
Incidence of malignancy were compared transplant recipients and general population, matched for age, sex and time after TX.
Results and discussion:
-Numbers of diagnosed number in the period 1980–1984 was low than because of incomplete recording.
-The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years)
– 5706 patients (15%) developed a cancer in this period.
– In 3276 patients, the first cancer registered following transplantation was a NMSC, and of these 426 were subsequently registered as having developed a different de novo cancer. Thus 2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer.
-Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
– the risk of NMSC in a transplant recipient is over 14 times that of the general population.
-The incidence rate of cancer in the transplanted population is twice the general population.
-nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma are the most common cancers in transplant population.
-The incidence of nonmelanoma skin cancer is much less in liver recipients -Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
-The incidence of oral cancer in liver recipients is high, more in patients with alcoholic liver disease.
-the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation.
-the SIR for non-Hodgkin’s lymphoma for all organs increases to a maximum at one year after transplantation and then declines.
-KTRs have higher rates of some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for others (Kaposi sarcoma, leukemia).
Factors affecting time to cancer diagnosis
many factors affected the incidence of post transplantation malignancy
-rates were greater in males than females,
-The incidence increased age.
-The risks of developing PTLD and kidney cancer have increased over the study period.
-Body mass index and whether or not a patient was on dialysis at time of listing for transplantation where available, did not significantly affect the hazard of cancer.
– incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data.
– NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
However, this risk may be underestimate since reporting of skin cancers may not be complete because some lesions will be removed or ablated without histological confirmation and some of the cancer registries did not collect data on basal cell carcinomas.
– incidence rates of many cancers in UK are similar to those reported by Canada, Australia and Sweden, but there are also some important differences.
– renal cell carcinoma showed higher rates in KTRs over the study period, the reason is not clear, may be due to increasing age of the recipient in whom renal malignancy is more common and in part the occurrence of cancer in acquired cystic disease of the native kidneys.
Also the registries do not distinguish between cancers arising in the native kidneys or in the transplant.
– weakness of the study is the lack of complete data on immunosuppression protocols and differences in induction and immunosuppression protocols in centers.
level of evidence II.
drawbacks when we use the registry data?
Variability in data collection.
Poor quality of data
Absence of follow up
selection bias
no control group
Introduction
It is a well-known side effect that following organ donation and the ensuing immune suppression, there is an elevated chance of developing de novo cancer. De novo malignancy in British solid organ transplant patients was the subject of this country-wide investigation. It contrasts the incidence rates of de novo cancer in patients who have received organ transplants with those in the general population.
Methods
All patients with an NHS number who underwent their first kidney, lung, liver, heart, or lung transplant in England, Wales, or Scotland between January 1980 and December 31, 2007, are included in the study. The cohort included 37 617 transplant recipients whose age and gender were known at the time of the procedure. The standardized incidence ratio (SIR) was used to compare the incidence of de novo malignancies to the overall UK population.
Results
Of the 37 617 patients who underwent transplantation, 67% received a kidney, 18% a liver, 10% a heart, and 5% a lung. 5706 individuals (15%) who underwent transplants later developed cancer. Non-melanoma skin cancer (NMSC) was the most prevalent type of cancer.
Overall, transplant recipients had a cancer incidence rate that was just over twice as high as the general population. The frequency of non-Hodgkin’s lymphoma grew to a maximum after 1 year following transplantation for all organ transplants, then it began to fall.
Following kidney transplantation, the SIR changed for some cancers, including Kaposi sarcoma and leukemia, and decreased for others, including NMSC, anal, cervical, Hodgkin’s lymphoma, kidney, oesophagus, and stomach.
The SIR for several malignancies (cervical, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma, and pancreatic) after liver transplantation peaked within 2 years following transplantation, then began to fall.
The SIR for bladder, lung, oral cancer, and Hodgkin’s lymphoma rose with time in patients who had heart and lung transplants.
Discussion
The total incidence of cancer (excluding NMSC) was more than twice the population average among transplant recipients who had received a heart, kidney, liver, and more than three times the average in individuals who had received a lung transplant. The most frequent kind of cancer seen in recipients of kidney and cardiothoracic transplants was NMSC. It is crucial to remember that not all cancer cases were reported to the appropriate authorities by the general public. Additionally, certain patients might have been exposed to carcinogens like cigarette smoke. The absence of comprehensive information regarding immune suppression was one of the study’s flaws.
In conclusion, the study proved that frequent NMSC screenings are necessary for all transplant patients. It was recognized that extra screening for cervical and breast cancer was unnecessary. To learn more about the advantages of early screening in immune-suppressed post-transplant patients, more research is needed.
This article is level II
Introduction
It is a known complication that there is an increased risk of developing de novo cancer after organ transplantation and the associated immune suppression. This was a national study of de novo malignancy in British solid organ transplant recipients. It compares the incidence rates of de novo malignancy in the general population with patients who have undergone organ transplantation.
Methods
The study consists of all patients transplanted in England, Wales and Scotland who received a first kidney, lung, liver, heart and/or lung transplant between January 1980 and 31 December 2007, who had an NHS number. The cohort consisted of 37 617 transplanted patients with known age and gender at transplantation. The incidence of de novo cancers was compared to the general UK population using the standardized incidence ratio (SIR).
Results
Out of the 37 617 transplanted patients, 67% received a kidney, 18% received a liver, 10% received a heart and 5% received a lung. 5706 (15%) patients developed cancer after transplantation. The most common cancer was a non-melanoma skin cancer (NMSC).
The overall incidence rate of cancer in transplanted patients was just over twice that of the general population. For all organ transplants, the incidence of non-Hodgkin’s lymphoma increased to a maximum after 1 year after transplantation, then declined.
After kidney transplantation, the SIR increased for some cancers, such as NMSC, anal, cervical, Hodgkin’s lymphoma, kidney, oesophagus and stomach, and it decreased for some cancers (such as Kaposi sarcoma, leukemia).
After liver transplantation, the SIR for some cancers (cervical, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas), peaked within 2 years of transplantation, then declined.
In heart and lung transplant recipients, the SIR for bladder, lung, oral cancer and Hodgkin’s lymphoma increased over time.
Discussion
The overall incidence of cancer (excluding NMSC) in recipients who had received a heart, kidney or liver transplant was over twice that of the general population, and over thrice in patients who received lung transplants. NMSC was the most common malignancy noted in kidney and cardiothoracic transplant patients. It is important to note that some cancers may have been under reported in the general population. Some patients may also have been exposed to carcinogens, such as cigarette smoke. One of the weaknesses of the study was the lack of complete data on the immune suppression.
In summary, the study confirmed that all transplant recipients should be screened regularly for NMSC. It was noted that there was no need to screen additionally for breast and cervical cancers. Further studies are required to provide additional information on the benefits of early screening in post-transplant patients receiving immune suppression.
Level of Evidence: II
Drawbacks of Registries:
Introduction
This study investigates the increased risk of de novo cancer in organ transplant recipients in the UK between 1980 and 2007.
In this study researchers compared, cancer incidence in transplant patients with the general population. this was aimed to better understand risks and inform the same to patients before transplantation.
Methods
The study considered factors such as age, gender, primary disease, smoking history, obesity, dialysis, and transplant year while doing analysis. A competing risks Cox regression analysis was used to model cancer incidence dependence on these factors. The analysis also compared immunosuppression usage in kidney recipients.
This study analyzed 37,617 organ transplant recipients in the UK between 1980 and 2007. Of these, 15% developed cancer during the follow-up period, with 3276 patients having their first post-transplant cancer as nonmelanoma skin cancer (NMSC).
The overall incidence rate of de novo cancer (excluding NMSC) in transplant recipients was more than double the general population’s rate. The risk of NMSC in transplant recipients was over 14 times higher than the general population.
Standardized incidence ratios (SIRs) were particularly high for NMSC, cancer of the lip, and Kaposi sarcoma. SIRs were greatest for lung transplant recipients and varied for different transplant types.
Discussion
Current study under discussion is probably the first detailed registry analysis of cancer occurrence in British organ transplant recipients, revealing distinct patterns of cancer occurrence among recipients of different organ types. The overall incidence of cancer (excluding non-melanoma skin cancer or NMSC) in heart, kidney, and liver recipients is more than twice that of the general population. The incidence is more than three times higher in lung or combined heart and lung transplant recipients.
NMSC came out to be the most common malignancy, with a significantly higher incidence among kidney and cardiothoracic transplant recipients compared to liver recipients.
It was also observed that transplant recipients experience a very high incidence of post-transplant lymphoma and Kaposi’s sarcoma, most probably due to aggressive immunosuppressive protocols and the development of antimicrobial drugs.
Weakness:
The findings of this study can help inform cancer surveillance programs and pre-transplant patient counseling on malignancy risks. All transplant recipients should be screened regularly for NMSC, lip, and anal cancer and encouraged to adopt lifestyle changes to reduce sun exposure.
Renal transplant recipients, particularly those with specific risk factors, may also benefit from regular ultrasound scans of their transplant and native kidneys, as well as cystoscopic examination of the urothelium.
What are the drawbacks when we use the registry data
Introduction :
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs. Understanding the increased risk and defining those cancers that are increased in these patients will inform the patient prior to transplantation and allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods:
The study cohort consists of all patients transplanted in England, Wales and Scotland who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007. The cohort consists of 37 617 transplanted patients with known age and gender at transplantation, followed up from the date of first reported de novo malignancy to the earliest date of death.
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). Cox regression models adjusted for recipient age group, gender, primary disease, smoking history, obesity, dialysis, and immunosuppression were used to test the hypothesis that the SIR is 1.0.
Results :
Of 37617 transplanted patients 67%receiving a kidney or simultaneous kidney ,pancreas , 18% a liver, 10% a heart and 5% a lung. A total of 5706 patients developed a cancer in this period, with the first cancer registered being a NMSC (C44). Ten years after transplantation, recipients have an overall incidence rate of 90%, more than double the 10-year incidence rate for the population of England. The overall incidence rate of cancer in the transplanted population is over twice that of the general population, with high incidence ratios for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma. Lung transplant recipients have the greatest SIR, while lymphoma rates are similar, except for non-Hodgkin’s lymphoma in cardiothoracic patients.
Discussion:
The incidence of cancer in British transplant recipients is over twice that of the general population, with NMSC being the most common malignancy. Heart transplant recipients receive higher levels of CNI triple therapy, while liver recipients receive a lower immunosuppressive burden. All transplant recipients should be screened regularly for NMSC, combined with lifestyle changes to reduce sun exposure, and there is no need for additional breast or cervical cancer screening.
.
What is the level of evidence provided by this article?
level 2 retrospective cohort
What are the drawbacks when we use the registry data?
Lack of data verification
Q1- Please summarise this article
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. In this study on cancer incidence in solid organ transplant recipients in Britain, the author describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs.
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of non melanoma skin cancer being 13 times greater. Non melanoma skin cancer, cancer of the lip, post- transplant lympho -proliferative disease and anal cancer have the largest standardized incidence ratios.
the incidence of different types of malignancy differs according to the organ transplanted.
Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient ,as well as for different malignancies.
Introduction
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated with immunosuppression.
Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
The overall SIR is greatest for lung transplant recipients.
For all organs, the SIR for non-Hodgkin’s lymphoma in creases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs.
Following kidney transplantation, the SIR increases for some cancers
(NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Impact of initial immunosuppression:
the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine
or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin.
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice
that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSCis the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens, Cigarette smoking, Primary sclerosing cholangitis, alcohol, Analgesic nephropathy or aristolochia use may necessitate renal transplantation, while being associated with transitional cell carcinoma of the native urothelium.
this study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC.
The incidence of posttransplant lymphoma in kidney recipients has increased nine fold since 1980–1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
The other cancer whose incidence is clearly increasing in renal transplant recipients over the study period is renal cell carcinoma.
One cancer whose incidence is not increased in this study , is breast cancer.
Another tumor whose incidence might be expected to be higher is cervical carcinoma, since it is known to be a consequence of papilloma virus infection .
the increased risk of cancer in transplant recipients is a reflection of being immunosuppressed rather than being attributable to any particular drugs, since patients immunesuppressed
as a complication of human immunodeficiency virus infection have a similar pattern of increased cancer incidence.
This Studies identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy.
Following transplantation,
This study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure (26). But , there is no need for any additional breast or cervical cancer screening.
Q2- What is the level of evidence provided by this article?
Level 2
Q3- What are the drawbacks when we use the registry data?
Drawback of registery studies
1- Retrospective study .
2- Heterogeneity of collected data .
3- Non conclusive and usually needs further well designed study to prove the result .
4- No control group.
5- No follow up result
Please summarize this article
Malignancies are more common in solid organ transplant recipients than general population. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period. Aim of the study was to compare incidence of de novo malignancy in solid organ transplant with general population and compere these incidences with different organs in the British population.
A cross sectional observational study with a cohort of all solid organ recipients between 1980 and 2007 (27 years, 37617 patients) was selected and cross referenced with cancer registries in in England, Wales and Scotland. Those patients diagnosed with malignancy in first month post-transplant were excluded. This incidence was compared to general population using standardized incidence ratio (SIR).
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL). Different factors appeared to affect the incidence of various cancers among these transplant recipients. In general, for all transplant recipients, the risk of cancer was higher in males than females, and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
Regular ultrasounds, surveillance of aerodigestive tract, and colonoscopy can be done for transplant recipients, to detect changes in favor of liver, lung, colon, kidney, or anal cancer. How helpful this is toward long term outcome is yet to be seen.
The limitations of this study mainly stem from the design and data collection method. The data was lacking key confounders such as history of smoking, history of dialysis before renal transplantation and incomplete data with regards to post transplant immunosuppression.
What is the level of evidence provided by this article?
Level II as it is a retrospective cohort study.
What are the drawbacks when we use the registry data?
1. Data are pre-collected by others than researchers. Necessary information may be unavailable or misclassified. Often hard to know exactly how data are generated. Limited to use variables in register. Variation in coding between persons and institutions
2. Lack of confounder information
3. Missing data difficult to handle. Difficult to know what missing data means and can lead to under coverage.
4. Low or unknown data quality
5. Unimportant differences become statistical significant
Please summarise this article
Introduction:
This study describe the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs. It is the first reported national study of de novo malignancy in British solid organ transplant recipients
Materials and Methods
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), has been linked to information on cancer registrations following solid organ transplantation recorded by cancer registries in England, Wales and Scotland between 1 January 1980 and 31 December 2007.
All patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD). The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR)
Results
What is the level of evidence provided by this article?
Level II
What are the drawbacks when we use the registry data?
Main drawback for using registry date is the variability in data collection from multiple sources and incomplete date or the risk of using a date that was inaccurately labeled with ICD codes in the registry. Selective bias is one of the important limitation that can occur with this kind of date.
: One of the side effects of immunosuppression treatment is increasing the rate of de novo cancer. In this study, using the UK Transplant Registry, the incidence rate of de novo cancer in transplanted patients was compared with the general population.
sixty-seven percent of the 37617 transplanted patients received a kidney with a median follow-up of 16 years. Fifty percent (5706) of the patients were affected by cancer. Most of them (3276 patients) had nonmelanoma skin cancer. The incidence rate was 90 per 1000 which was more than double of the ten-year incidence in the general population.
Q2: This is a longitudinal cohort study (Level II).
Q3: Limitations include:
no active follow-up
Variable data collection
selective bias
incomplete data
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ:
A UK Registry Audit
Introduction
de novo cancer development is an established complication of organ transplantation and immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will inform the patient prior to transplan- tation and allow a rational approach to screening and surveillance in the postoperative period.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland and Wales.
Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period.
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
The cohort consists of 37 617 transplanted patients with known age and gender at transplantation. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Inclusions criteria:
Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients.
patients whose first reported cancer following the date of transplantation is an in situ tumor ,a benign tumor or a tumor of uncertain or unstated behavior ,the date and code of any subsequent malignant tumor was used.
The time to first occurrence of a nonmelanoma skin cancer (NMSC) was obtained for all individuals whose first registration was this cancer.
Exclusion criteria:
The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).
all patients with cancer diagnosis within one month of transplant were excluded, except for the 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD), defined as the occurrence of Hodgkin’s or non-Hodgkin’s lymphoma.
Results:
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period.
the first cancer registered in 3276 patients following transplantation was a NMSC .
2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer.
Ten years after transplantation, recipients have an overall incidence rate of 90 per
thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period.
NMSC is much more common, and the corresponding standardized incidence was 14.4 meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population.
The overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients.
The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients.
Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease.
the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower.
the SIR for non-Hodgkin’s lymphoma for all organs increases to a maximum at one year after transplantation and then declines.
The patterns in the incidence rates of many other malignancies vary between organs.
Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily.
In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer.
the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Factors affecting time to cancer diagnosis
Age
Gender
Body mass index
whether or not a patient was on dialysis at time of listing for transplantation
For recipients of a liver, recipient age group and primary disease affected the risk of skin cancer and colorectal cancer .
The risk of PTLD only depended on recipient gender ,and the risk of lung cancer depended only on recipient age group .
For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients.
Impact of initial immunosuppression
the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data for reliable estimates.
What is the level of evidence provided by this article?
Level 2
Drawback:
No active follow up
Retrospect data
Selective bias
Variable data collection.
Summarise this article :
INTRODUCTION:
Impact of organ transplantation and the ensuing immunosuppression is an increased risk of cancer.
It’s necessary not only to educate the patient prior to transplantation but also to provide a practical method for screening and surveillance throughout the postoperative period
METHOD:
The incidence of de novo malignancies in allograft recipients has been described in this study on the cancer incidence in solid organ transplant recipients in Britain, and occurrences following the transplantation of various organs have been compared.
Using standardized incidence ratios that were matched for GENDER, AGE and TIME PERIOD, incidence rates in the transplanted group were then compared with those in the general population.
RESULT:
Result concludes that in transplant patients, de novo cancer occurs twice as frequently (10 times more frequently) as in the general population, with nonmelanoma skin cancer occurring 13 times more frequently.
The biggest standardized incidence ratios are for nonmelanoma skin cancer, lip cancer, posttransplant lymphoproliferative illness, and anal cancer, however, the incidence of various malignancies varies depending on the organ that was transplanted.
Varied types of transplant recipients and various malignancies show different trends in standardized incidence ratios during the years following the transplant.
Conclusion:
A heart, kidney, or liver transplant recipient’s overall risk of developing cancer is more than twice that of the general population, and a lung transplant recipient’s risk of developing cancer is more than three times greater.
The most prevalent kind of cancer among transplant recipients is Non Melanoma Skin Cancer
Frequent NMSC screening, lifestyle adjustments to decrease sun exposure especially use of sun block and regular alcohol surveillance in patients having liver transplants all contribute significantly to the goal of early cancer detection.
The level of evidence provided by this article:
Level II (Retrospective cohort study)
The drawbacks when we use the registry data:
observational study of level 1 evidence
Data on immunosuppression is not available
Possible influence of confounders
Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
Introduction
To evaluate the incidence of de-novo cancer in the general population and solid organ transplant recipients and to compare the incidence of de-novo cancers among different organ transplantation.
Methods
This is a retrospective cohort study for all solid organ transplant recipients obtain data from cancer registries in England, Wales and Scotland.
In this study standardized Incidence Ratios matched for age, gender and time period were used to compare de-novo malignancy in solid organ transplant recipients with general population.
Results
Among 37617 transplanted patients 67% kidney, 18% liver, 10% heart, and 5% of lung transplant. Median follow up was 16 years.
15% patients develop cancer in this time frame.
3276 patients got first time cancer and registered.
The most common cancer is non-melanoma skin cancer and its incidence is higher than that of general population.
Conclusion
The study identify patient groups and cancer types, aids in surveillance programs, and provides information on warning transplant candidates about the possibility of cancer
Level IV evidence
Data from multiple sources and countries
There can be selection bias
Incomplete data
Incomplete or loss to follow up
Potential outcomes maybe lacking
Summary of the article:
study type – Retrospective analysis (cohort study) of UK cancer registry audit
published in Am J Transplant 2010
Introduction
An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
Understanding the increased risk and identifying cancers increased in transplant recipients will help in pretransplant counselling of patients and as well as to develop rational approach for cancer screening and surveillance in the post- transplant patients.
Most of the available studies on the incidence of de novo cancer following transplantation are usually limited because they are generally single-center studies, in a specific form of malignancy (kidney / liver / thoracic), or of limited duration follow-up.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods
Data of transplant recipients in the UK held by NHS-Blood & Transplant registry was linked to information on cancer registrations by the 10 cancer registries (8 in England, 1 in Wales and 1 in Scotland) using the NHS number.
Study period – Jan 1980 – Dec 2007
Inclusion criteria:
Excluded are –
Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR).
Patterns in cancer incidence over the time period following transplantation have been evaluated by further stratifying the SIRs by year since transplantation.
This analysis extended to 15 years following transplantation, and was carried out for each organ and all the different cancers.
Results and discussion
Trends of cancer development with time
Conclusions:
This study identifies patient groups and cancer types for cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy.
All transplant recipients should be screened regularly for NMSC, lip and anal cancer, and it should be combined with lifestyle changes to reduce sun exposure
No need for any additional breast or cervical cancer screening.
Patients undergoing liver transplant for alcohol should have regular surveillance of the aerodigestive tract
2.What is the level of evidence provided by this article?
Level 2 (Retrospective Cohort study)
3.What are the drawbacks when we use the registry data?
Please summaries this article
Publised in American Journal of Transplantation 2010; 10: 1
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression. Understanding the increased risk and defining those cancers that are increased in these patients will not only inform the patient prior to transplantation but also allow a rational approach to screening and surveillance in the postoperative period.
So, this study examined and compared the rates after different organ transplants. This study included data from 10 cancer registries (8 from England, 1 from Wales, and 1 from Scotland) from 1980 to 2007. 37,617 first-time kidney, liver, heart, or lung transplant recipients were included.
All patients transplanted in England, Wales, and Scotland between 1 January 1980 and 31 December 2007 who got their first kidney, liver, heart, or lung transplant and had an NHS number are included in the study cohort. Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR). Ten years after transplantation, recipients have an overall incidence rate of 90 per
Results
The study found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to the UK.
Time trends following transplantation.
Limitations
Conclusion
Following transplantation, this study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure.
What is the level of evidence provided by this article?
Level 2
What are the drawbacks when we use the registry data?
SUMMARY
Introduction
One of the known complications of solid organ transplantation is the development of cancer due to the immunosuppressive effects of medication used during and after the surgery. Most of the available studies on the incidence of de novo cancer following transplantation are usually limited because they are generally single-centre studies, specific to a form of malignancy, and of a limited follow-up duration.
The British solid organ transplant recipients make comparisons with incidence rates in the general population and compare these incidences following the transplantation of different organs.
Materials and Methods
Inclusion criteria:
Exclusion criteria
Results and discussion
Conclusion
The study has not only shown the occurrence of de novo malignancy following organ transplantation, but it has also demonstrated the incidence rate of various malignancies in different types of organ transplantation and the possible etiology or association responsible for the malignancies.
The level of evidence is 2
Drawbacks of registry data
1. Introduction
Malignancy post organ transplantation is an established complication.
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater . In this particular study and for the first time they compared the incidence of de novo postranspalnt cancers to the incdence in the general population and also compared the incidence following different organ transplants. Aim of the study:
-Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs. Method:
This is a cohort study, this data was taken from NHS registry and other consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007. Result:
37617 transplants 25 104 (67%) received a kidney, 18% alive 10% heat, 57% lung follow-up period 16 years.
5706 patients 15% developed cancer in this period.
In 3276 patients first cancer registered of 426 developed a different de novo cancer.
Transplant population cancer incidence is twice that general population. 2. What is the level of evidence provided by this article?
Level of evidence: Level 2 – retrospective cohort study
3. What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
1 Variable quality of the data.
2 lost to follow-up on long-term
3 Lack of control group
4 Bias due to heterogeneity of data
article is based on UK population
shows incidence of cancer post solid organ transplant
voluntarily reported
may lead to underestimation
SIR of various tumor are shown
all patients with cancer diagnosis within one month of transplant
were excluded, – so pre existing tumour were ruled out
Of the 37 617 transplanted patients, 25 104 (67%) received
a kidney transplant
16 yrs median follow up
15% develop cancer
The overall incidence rate of cancer in the transplanted
population is just over twice that of the general population.
The SIR is particularly high for
nonmelanoma skin cancer, cancer of the lip and Kaposi
sarcoma.
SIR is highest in lung transplant
in liver transplant , NMSC and lip cancer is less compared to other cancer
following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney,
oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia).
SIR is higher for male
SIR generally decreases with age
recipient more than 50 yrs – NMSC and PTLD SIR is high but for other tumour SIR is not high
LIMITATION
incidence rate of cancer may be underestimated as second cancer of same patient is not taken in account
observational study of level 1 evidence
data on immunosuppression is not available
1. Please summarise this article
Introduction
· A documented impact of organ transplantation and the ensuing immunosuppression is an increased risk of cancer.
· It’s important not only to educate the patient prior to transplantation but also to provide a practical method for screening and surveillance throughout the postoperative period
Method
· The incidence of de novo malignancies in allograft recipients has been described in this study on the cancer incidence in solid organ transplant recipients in Britain, and occurrences following the transplantation of various organs have been compared.
· Using standardized incidence ratios that were matched for age, gender, and time period, incidence rates in the transplanted group were then compared with those in the general population.
Result
· In transplant patients, de novo cancer occurs twice as frequently (10 times more frequently) as in the general population, with nonmelanoma skin cancer occurring 13 times more frequently.
· The biggest standardized incidence ratios are for nonmelanoma skin cancer, lip cancer, posttransplant lymphoproliferative illness, and anal cancer, however, the incidence of various malignancies varies depending on the organ that was transplanted.
· Varied types of transplant recipients and various malignancies show different trends in standardized incidence ratios during the years following the transplant. The ramifications of these findings extend to a countrywide screening program.
Conclusion:
· A heart, kidney, or liver transplant recipient’s overall risk of developing cancer is more than twice that of the general population, and a lung transplant recipient’s risk of developing cancer is more than three times greater.
· The most prevalent kind of cancer among transplant recipients is NMSC.
· Regular NMSC screening, lifestyle adjustments to decrease sun exposure, and regular alcohol surveillance in patients having liver transplants all contribute significantly to the goal of early cancer detection.
2. What is the level of evidence provided by this article?
Level II (Retrospective cohort study)
3. What are the drawbacks when we use the registry data?
· Variable quality of the collected data, and a lack of active follow-up
· Additional work for data collection
· Possible changes in the long term (accounting system, classifications)
· Possible influence of confounders
· Need for external and internal validation of collected data
· Often no data monitoring/validation; different local conditions in data collection and submission
· Target population depends on external validity (participating healthcare special disciplines)
· Non-homogeneous definition and scope of international registry items
· Complex data privacy issues
· Complete and long-term follow-up remains challenging
· Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
Introduction
Malignancy post organ transplantation is an established complication could be associated with certain viral infection or a results long standing immunosupression .
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater .
The incidence of different types of malignancy differs according to the organ transplanted .
Methodology :
The population of this study consists of all patients transplanted in England, Wales
and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
Cancer incidence in the transplant population was compared with the general
UK population using the Standardized Incidence Ratio (SIR) .
Analysis :
1- Number of transplantations : 37 617 with follow up period 16 year
2- Total number of cancer : 5706 ( 15 % )
3-
Introduction
· It is known that organ transplantation and immunosuppression increased risk of de novo cancer.
· It is important to get full knowledge about cancer risk to inform recipient and for screening post transplantation.
Aim of the study
Study the incidence of de novo malignancies in transplant recipients and a comparison of these incidences in different types of organ transplant
Materials and Methods
· all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number
· Those who received a combined heart and double lung transplant were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant were taken to be kidney recipients
· Exclusion of recipients of a pancreas alone and all other multi-organ transplant
Discussion
· The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population and over three times higher in recipients of lung or combined heart and lung transplants
· NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
· The incidence of non-Hodgkin’s lymphoma and kidney cancer was different between countries
· the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC
· The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984
· Breast cancer found to be not increased
Weakness of the study
· lack of complete data on immunosuppression
· There was a difference the induction and maintenance immunosuppression between heart and liver transplantation
· the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded
CONCLUSION
· all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure
· there is no need for any additional breast or cervical cancer screening
This is a retrospective cohort study level 2
What are the drawbacks when we use the registry data?
· necessary information may be unavailable
· data collection is not done by the researcher
· confounder information is lacking
· missing information on data quality
· truncation at start of follow-up making it difficult to differentiate between prevalent and incident cases and the risk of data
An increased risk of developing de novo cancer is a well-known complication of solid organ transplantation and the associated with use of immunosuppression.
Non-Melanoma Skin Cancer was the most common malignancy with SIR of 16 especially for renal and cardiac recipient that is 3 times higher than others organ transplants.
for all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs.
Results:
-The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants, the incidence of Non-Melanoma Skin Cancer is 13 times that of general population, the incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of immunosuppression induction and avoidance of azathioprine in maintenance immunosuppression because azathioprine increase the risk of skin cancer.
Conclusion:
in conclusion this study helps to determine of post solid organ transplant cancer surveillance, screening programme and protection.
2.What is the level of evidence provided by this article?
This article is a retrospective cohort study.
3.What are the drawbacks when we use the registry data?
Lack of follow up, lack of complete data.
Title: Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit
Introduction: Organ transplantation is associated with an increased risk of malignancy. It is important to understand the magnitude of the elevated risk and those cancers that are increased in the post-transplant period for adequate counselling and surveillance.
Methodology: Collette et al in this prospective cohort study, examined the incidence rate of new onset malignancy in British solid organ transplant recipients and compare with incidence in general population. Incidence rates of malignancies were also compared between the difference solid organ transplantations.
The study participants were 37,617 patients who had first kidney, liver, heart or lung transplants in the UK between 1 January 1980 and 31 December 2007. Five hundred and fifty-three participants who had heart-lung transplantation were classified as lung transplant recipients and 764 with combined pancreas kidney transplant were grouped as kidney transplant recipients. The study participants were followed up from the date of first transplant to the earliest date of first reported de novo malignancy, or date of death within the study period. All study participants who had a cancer diagnosis within one month of transplant were excluded except for the 620 participants diagnosed with post-transplant lymphoproliferative disease (PTLD).
Results: Majority of study participants received a kidney transplantation (or simultaneous kidney and pancreas), 25 104 (67%), followed by liver (18%) a liver. Ten percent and five percent received a heart and a lung (or heart/lung) respectively. The median follow-up period was 16 years (interquartile range: 8–26 years). Fifteen percent (5706) developed a cancer in this period. Non-melanoma skin cancer was the first registered cancer following transplantation in 3276 patients out of which 426 were de novo.
At 10 years after transplantation, overall incidence rate was 90/1000 patients which is more than twice the 10-year incidence rate for the population of England which was 36 in the same period. Non melanoma skin cancer has a standardized incidence rate of 14.4 (95% confidence interval: 13.8–15.0).
In the transplanted population, the overall cancer incidence rate is about twice that of the general population. Non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma have exceedingly high standardized incidence ratios (SIR). Lung transplant recipients have the highest SIR overall. Non-melanoma skin cancer has a much lower incidence in liver recipients, likewise the SIR for cancer of the lip in liver transplant recipients is less than half that for other transplant recipients. Generally, lymphoma rates are similar, however, non-Hodgkin’s lymphoma has a higher incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver transplant recipients were noted to have high incidence of oral cancers majorly in those who had alcoholic liver disease.
The SIR for non-Hodgkin’s lymphoma increases to a maximum at 12 months after transplantation for all organ recipients and then declines but varies with other malignancies. After kidney transplantation, the SIR increases for many cancers (non-melanoma skin cancer, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for few (Kaposi sarcoma, leukemia). The SIRs for liver and ovarian cancer increase in the early years after transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer is unchanged.
After liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 24 months of transplantation, and then steadily declines. The SIR for bladder, lung and oral cancer and Hodgkin’s lymphoma, increase over time following heart transplantation whereas those for most other cancers remain stable or decrease.
Generally, SIRs for each cancer decrease with increasing age, and higher rates in males. However, NMSC and PTLD in recipients aged over 50 are similar to general population.
Body mass index and commencement of dialysis had no effect on the hazard of cancer. The incidence of non-melanoma skin cancer in kidney transplant recipients was not affected by the type of immunosuppressive medications used at 3 months post transplantation.
Conclusion: This is first detailed registry study of pattern of post transplantation malignancy cancer in British transplant recipients. It revealed the varying patterns of cancer occurrence in recipients of different organ types. The overall incidence of non-melanoma skin cancer (NSMC), in recipients of a heart, kidney or liver, is more than double that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and more than triple in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the commonest malignancy, risk is 16 times higher in kidney and cardiothoracic transplant recipients compared with the general population, but 3 times higher risk in liver transplant recipients. Limitations in reporting of cases of malignancies and early treatment of skin lesions might have reduced the reported incidence rates of skin malignancies. Likewise, in the general population, new onset skin cancers may also be underreported.
Liver recipients have a lower incidence of cancer of the lip and anal canal which may be as a result of the lower immunosuppressant dose in transplant protocol.
Level of evidence is 2
Limitation
Lost dataPoor reporting of casesIt is disease specificIt requires resources for data entering and storage over time.
Introduction:
increased risk of de novo cancer is a well known complication of organ transplantation. It is paramount to understand this risk and identify these cancers to make transplant candidate aware of the problem ahead of receiving the transplant and allow for the emergence of guidelines to cancer screening in the post transplant period.
In this particular study and for the first time they compared the incidence of de novo postranspalnt cancers to the incdence in the general population and also compared the incidence following different organ transplants.
Methods:
They linked the UK transplant registry to registry data of post solid organ transplant cancer informations in the England, separate data for Wales and Scotland using the INH number. This included all patients who received their first kidney, liver, heart or lung transplant between January 1980 and December 2007.This study included 37617 transplanted patients (67%) received a kidney or simultaneous kidney and pancreas,18% a liver,10% heart and 5% a lung or ( heart and lung).The median follow up for this cohort of patients was 16 years ( range 8- 26 years).
Statical Methods:
Cancer incidence in the post transplant period was compared to the general population using the Standardized Incidence Ratio (SIR).
Results:
During the follow up period 15% developed cancer.The first cancer registered was NMSC
The 10 – year incidence of de novo cancers in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 fold increased. NMSC ,cancer of lip, PTLD and anal cancer have the largest SIR, but the incdence of malignancies differ according to the type of organ transplanted. The overall SIR is greatest for lung transplant recipients. The incidence of NMSC is much less in liver transplant recipients. Lymphoma rates are similar between different organ transplants except for non- Hodgkin Lymphoma has greater incidence in cardiothoracic transplant recipients.
Patterns for SIRs over time since receiving the transplant are different for different types of transplant recipients and for different malignancies.
For each type of cancer the incidence is greater in males than females and increased with increasing age. The risks of developing PTLD in renal transplant increased with duration of follow up.
Regarding impact of IS ,the incdence of NMSC in kidney transplant recipients was not affected by whether azathioprine or MMF was used at 3 months nor was it affected by the use of tacrolimus or cyclosporine. For other types of cancers data was not available.
Conclusion:
The results of this study helps developing of post organ transplant cancer surveillance and screening programme.
2 level of evidence:
3. limitations of the study:
The use of regisry data:
A. under estimation of incidence of cancer.
B. Important data missing like the impact of IS treatment on incidence of cancers.
C. Lack of informations regarding other cancer risk factors like cigarette smoking,sun exposure and alcohol
D. Lack of actual follow up.
what is good about the study:
1. comparing incdence of post transplant denovo cancer with the with that of the general poulation.
2. Lager number of cohort.
3. Longer duration of follow up.
4. Coming up with results that has implications on post organ transplant cancer screening.
-Level of evidence is 2
-The aim of the study was to compare cancer incidence in “solid organs transplant recipients” to that of general population .
-This Cohort study included 37617 solid organ transplant recipients .
-The study concluded higher incidence of cancer in lung recipients ( 3 times ) , liver , kidney and heart recipients ( 2 times ) compared to general population .
– NMSC, kidney ,Hodgkin’s ,and oesophageal cancers were higher in renal recipients than the general population .
-Non melanocytic skin cancer was Lower in liver recipients than kidney ones due to relatively lower IS protocols .
-Increased incidence of post-transplant lymphoproliferative diseases over the past few years.
1.Please summarise this article?
Introduction:
Post transplant denote malignancies is a well known complication of transplantation ( due to high doses of immunosuppression). Pre-transplant patient counciling about risk of malignancy development and need for post transplant screening and surveillance are crucial.
Aim of the study:
-Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs.
Method:
-Cohort study include all solid organ transplant recipients (first liver, heart, lung and kidney transplant) in UK, Wales and Scotland, from 1Jan 1980 to 31Dec 2007.
-37617 recipients included who have NHS number.
-Combined heart and double lung transplantation considered as lung transplant, combined pancreas and kidney transplantation deal with as kidney transplantation.
-Pancreas alone & all other multi organ transplant recipients were excluded from the study.
Results:
-The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants
-The incidence of NMSC is 13 times that of general population
-The incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of biological induction and avoidance of azathioprine in maintenance immunosuppression
-The most common malignancies occurring in renal transplant recipients in the current study are NMSC, PTLD, lip and anal cancer and RCC, on the other hand the incidence of breast cancer is not increased due to unclear reason and the incidence of cervical cancer also is not higher which may be explained by active surveillance programs.
Conclusion:
-The study identify patient groups and cancer types, helps in surveillance program, and providing data on counselling pretransplant patients on the risk of malignancy.
-All transplant patients should be screened regularly for NMSC, oral and anal cancers, combined with lifestyle changes prevents sun exposure.
Limitation:
-Absent data about IS protocols.
-Underestimation of cancer incidence because it collected data about first de-novo cancer, so second cancer will not be recorded.
-Early detection of cancer in such patients does not translate to superior cure.
2.What is the level of evidence provided by this article?
-Level of evidence is 2
3-What are the drawbacks when we use the registry data?
-The validity and generalizability of the registry.
-Absence of an appropriate comparison group.
-Variable quality of the collected data.
-Lack of active follow-up (which may underestimate rates of adverse events).
-NO specific tool exists for assessing the quality of a registry-based study.
1)Please summarise this article
This paper uses data from the UK transplant registry and national cancer registries in England, Scotland and Wales to examine the incidence of first-onset of de novo cancer in solid organ transplant patients: liver, kidney (including combined kidney/pancreas), lung (including combined heart/lung) and heart) who received a first transplant between 01.01.1980-31.12.2007. The outcome measured was timing of detection of de novo cancer post-transplant, or in the case of the first cancer being non-melanoma skin cancer (NMSC) the timing of detection of any second NMSC. Results were compared to the general population in the UK using standard incidence ratios (SIR).
The importance of this paper in comparison to previous studies is that it provided a large sample (37 617 transplanted patients) with a well-defined reference population (general UK population). This contrasted previous studies which were restricted either by being smaller studies or single organ type, or which used data from various different countries thereby making the reference general population harder to define. Although registry data is often limited by inherent bias in the available or missing data (see question 3), the authors of this paper hoped their results would be more reliable than studies using international registries such as the Israel Penn International Transplant Tumour Registry (IPITTR) because reporting to the latter is voluntary and likely to contribute to underreporting of true cancer incidence.
There remained, however, significant limitations in the registry data analysed by the authors of this paper and this included unavailability of smoking history for kidney transplant recipients, missing data on increased BMI (an acknowledged risk factor for development of certain cancers) and <50% of patients having available data on the immunosuppression they were taking 3 months post-transplantation.
Key results:
· 15% of patients developed a de novo cancer, and approximately half of these patients were registered with a cancer other than NMSC
· 10 years after transplant the incidence of de novo cancer for solid-organ transplant recipients in the UK was more than double that of the general population
· The incidence of NMSC is much higher in the transplant population (SIR 14.4)
· SIRs are also high for Kaposi’s sarcoma and cancer of the lip in transplant patients
· There is some variation depending on the type of solid organ transplant, with, for example, overall de novocancer incidence being highest in lung transplant recipients and lower rates of NMSC in liver transplant recipients
· For kidney transplant recipients, they have higher SIRs of the following cancers: NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach
· Undergoing solid organ transplant at a younger age is linked to a higher risk of developing de novo cancer compared to an age-matched general population, whereas after the age of 50 the incidence of de novo cancer (excluding NMSC and PTLD) is more similar to that of the general population
· The incidence of breast cancer was not increased in the transplant population
2)What is the level of evidence provided by this article?
This article is a retrospective cohort study which according to the hierarchy of evidence provides a higher level of certainty than case-control studies, case reports and expert opinion but is nevertheless inferior to randomised controlled trials and systematic reviews.
3)What are the drawbacks when we use the registry data?
Post-transplant malignancy is a recognised long-term complication of solid-organ transplantation, with efforts to determine the standardised incidence ratio (SIR) being relevant to pre-transplant patient counselling, determination of optimal treatment protocols and informing surveillance/screening programmes. Given the relatively low incidence of post-transplant malignancy overall, registry data offers the obvious advantages of providing a large cohort reflecting multi-centre experience and is the method of choice for many studies examining incidence of rare phenomena on a population level. However, as attractive as the large data set may initially seem, it comes with several disadvantages and may lead to inherent bias. Some of these disadvantages can be seen within this article:
1. Incomplete data entry which might lead to unintended bias e.g.
– Under-reporting of incidence of certain type of cancer
– Missing information on population demographics e.g. smoking history
– Data entry from some centres may be incomplete
– It may be hard to establish a truly comparable control group e.g. the ‘normal population’ for comparison in this article was taken from national cancer registries where incidence of skin cancers may be significantly under-reported
– Forms which require coded entries may lead to various interpretations by different people entering data- the registry data may not be truly standardised
2. Retrospective analysis with study findings potentially being restricted by the type of data collected in the registry and additional detail cannot be easily accessed e.g. for this particular article it was not possible to collect data on the immunosuppression used in those patients who had developed cancers
3. Analysed data often spans large timeframe during which there might have been significant changes in the management of patients (e.g. immunosuppression protocols, screening programmes)- deciding which timeframes to include/exclude can potentially result in misleading conclusions
4. Looks at observational data which is often analysing association but does not provide evidence for cause and effect
Numerous studies have investigated cancer incidence in recipients of a kidney, liver or cardiothoracic organ, but these often focus on a single transplant type, a specific form of malignancy, experience at a single center, or a limited duration of follow-up. National studies, based on registry data, have been reported for kidney transplant recipients in Canada , Sweden , Japan , Finland ,Australia and the USA
This first detailed registry study of cancer occurrence in British transplant recipients has shown evidence of different patterns of cancer occurrence in recipients of different organ types. The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6). NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
The incidence rates of many cancers that we are reporting for theUKare similartothosereportedbyCanada, Australia and Sweden, but there are also some important differences. We have found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to the UK. The incidence rates for a number of cancers reported in the US study ,are considerably higher than those found in other countries. In particular, the high rates of hepatobiliary, pancreatic, prostate, kidney, uterine and cervical cancer have not been seen in the UK.
Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens. Cigarette smoking, for example, may contribute to the requirement for lung transplantation (emphysema) or heart transplantation (ischaemic cardiomyopathy), while also being associated with an increase in risk of many cancer types. Primary sclerosing cholangitis may require liver transplantation, but is also associated with colitis, which might account for the increase in incidence of cancer of the colon and rectum; likewise alcohol (and the exposure to cigarette smoking which accompanies it) may account for the higher risk of oral cancer in liver recipients
As expected the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC. The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
One cancer whose incidence is not increased in our study, and indeed which may be less common, is breast cancer. The reason for this is not clear, but the finding is consistent with data from an earlier report from the Collaborative Transplant Study registry (recipients between 1983 and 1994 from Europe and North America) but not the most recent US analysis (recipients 1995–2001) in which the incidence of breast cancerwas twice that of the normal population, a similar rise to that noted with other cancers
Aweakness of the study is the lack of complete data on immunosuppression. Heart transplant recipients have generally received biological agents such as antithymocyte globulin for induction with higher levels of calcineurin inhibitor (CNI) based triple therapy than recipients of other organs. In contrast, liver recipients receive a lower immunosuppressive burden using protocols, which involve tapering to CNI monotherapy (usually tacrolimus) in all but autoimmune liver disease.
Studies such as ours identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy. Following transplantation, our study confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure However, there is no need for any additional breast or cervical cancer screening.
What is not so clear is how to manage the increased risk of other cancers, which, in spite of having a higher incidence than the normal population, are uncommon
Also uncertain is whether the benefits of early cancer detection in this immunosuppressed population translate into superior cure rates.
level II
1. Please summarize this article.
The main aim of this article is to compare with general population and risk of developing of de-novo malignancy post-transplantation.
Post-transplant tumor incidence is twice as compared to general population and nonmelanoma skin cancer being risk 13 times more compared to normal population according to nomenclature.
The overall incidence rate of cancer post-transplant is 90/1000, the lymphoma incidence has increased 9 folds since 1980-1984.
This study data was taken from NHS registry and other countries that consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007.
The pattern and incidence ratios over time increases and differ for different types of transplant recipient and tumors.
In this article the data were taken from NHS blood and transplant registry of different countries, in the recipient ten year incidence of denovo tumor was twice that of general population.
The incidence of cancer post-transplant was compared to general population using standardized incidence ratio that were gender, age and time period matched.
Statistical Method;
This is a cohort study, this data was taken from NHS registry and other consists of all the patients transplanted in UK, Wales, and Scotland from 1 January 1980 and 31 December 2007.
The data was information of cancer was obtained from age, gender, and time of cancer occurrence.
Following transplantation the pattern of cancer incidence have been evaluated by further stratifying the SIRS and P- values for testing the hypothesis were 1.0 obtained.
Results;
The total number of patients were 37617, of them 67% received both kidney+ pancreas, 18% a liver, 10% received heart, and 5% a lung. The median follow up period 16 years, out of these recipients total 15% (5706) developed a cancer, the de novo cancers 426 developed skin cancer and 2856 were registered with nonmelonoma skin cancer.
Impact of initial use of immunosuppression;
There was no any association of NMSC in immunosuppression in first three months, otherwise insufficient data about other cancers.
Discussion;
The British transplant detailed registry study evidence showed there is occurrence of cancer in different pattern in transplant recipient in different organ types.
NMSC was the most common malignancy with SIR of 16 especially for renal and cardiac recipient that is 3 times higher than that of others.
The incidence is equal many centers like Sweden and Australia with few differences like they found higher incidence of certain cancer in different countries. They did not found any certain association of risk factor.
Limitation;
There was lack of detailed information about immunosuppression.
Induction was different for heart transplantation and different for other organs.
Maitianence immunosuppression was higher for heart transplantation.
The first cancer incidence occurrence except NMSC was not recorded.
Level 2.
Please summarise this article.
This is a longitudinal observational cohort study than include all UK post transplant patients from 1980-2007(NHSBT), comparing the incidence of De novo malignancy in SOT to general population by using SIR(Standardized Incidence Ratio)
10 years incidence of De novo malignancy in post transplant Solid Organ was two times higher than general papulation with NMSC the most common form of malignancy.
What is the level of evidence provided by this article?
Level 2(retrospective cohort study)
What are the drawbacks when we use the registry data
Summary of Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry AuditIntroduction:-
Most of the studies’ incidences of cancer in recipients focus on a single transplant type, a specific type of malignancy a single center, or a limited duration of follow-up.
Registries, such as that of the intentional society of heart and lung transplantation, cover a number of countries, so it is not clear what the referral population should be.
This is the first repeat national study of de novo malignancy in British solid organ transplant recipients that make compassion with the incidence rate in the general population and compare this incidence following the transplantation of different organs.
Methods and material
The cohort consists of 37 617 transplant patients with known age and gender at transplantation patients were followed up from the date of first transplant to earliest of the date of first repeat de novo malignancy a date of death within the study period.
Statistical methods
Cancer incidence in the transplant population was compared with the general UK population using the standardized incidence ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study chart to the expected number in the general population.
Results
37617 transplants 25 104 (67%) received a kidney, 18% alive 10% heat, 57% lung follow-up period 16 years.
5706 patients 15% developed cancer in this period.
In 3276 patients first cancer registered of 426 developed a different de novo cancer.
Transplant population cancer incidence is twice that general population.
The standardized ratio is high for non-melanoma skin cancer such as the hip and Kaposi sarcoma
impact of initial immunosuppression.
The incidence of NMSC in Kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor unaffected by the use of TAC or ciclosporin.
Discussion
This first detailed registry study of cancer occurrence is the British transplant recipient has shown evidence of different patterns of cancer occurrence in recipients of different organ types.
Some diseases for such transplantation is undertaken may be associated with malignancy elsewhere as aggregate smoking, primarily sclerosing cholangitis and analgesic nephropathy.
The pattern is similar after lung transplantation, with the exception that there is less evidence of a time-dependent increase in the SIR for leukemia and lung cancer.
A liver transplant has a higher risk of skin cancer with increasing age.
The level of evidence
level 2
What are the drawbacks when we use the registry data?
Heterogenous data collection with retrospective studies
Follow-up on long-term participation was lost.
Variability of quality of data.
An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression.
The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer being 13 times greater. Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease.
the incidence rate, compared to the general population, quickly increases to twice that of the general population following kidney or heart transplantation. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower.
For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs. Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia). The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily. In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease. The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients. This increased incidence may be an underestimate since reporting of skin cancers may not be complete because some lesions will be removed or ablated without histological confirmation and some of the cancer registries did not collect data on basal cell carcinomas.
level of evidence 2
☆Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit.
▪︎This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Introduction:
▪︎An increased incidence of malignancy is an established complication of organ transplantation and the associated immunosuppression.
◇Results:
▪︎This study on cancer incidence in solid organ transplant recipients in Britain,
described the incidence of de novo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs.
▪︎Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland
and Wales.
▪︎Incidence rates in the transplanted population were compared with the general population, using standardized incidence ratios matched for age, gender and time period.
▪︎The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence
of nonmelanoma skin cancer being 13 times greater.
▪︎Nonmelanoma skin cancer, cancer of the lip, posttransplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted. Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies.
▪︎These results have implications for a national screening program
◇ Weaknesses f the study:
▪︎The lack of complete data on immunosuppression.
▪︎It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
▪︎The increased risk of cancer in transplant recipients is a reflection of being immunosuppressed rather than being
attributable to any particular drugs,
◇ The strength of this study:
▪︎Identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pretransplant patients on the risk of malignancy.
▪︎ It confirms that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle
changes to reduce sun exposure. However, there is no need for any additional breast or cervical cancer screening.
◇ Important recommendations of the study:
▪︎Patients undergoing liver transplant for alcohol should have regular surveillance of the aerodigestive tract.
▪︎Patients with primary sclerosing cholangitis who have their colon and rectum in situ should undergo regular colonoscopy.
▪︎The presence of recurrent graft
cirrhosis should also be a cue to regular ultrasound surveillance for hepatocellular carcinoma.
▪︎Similarly a case can be
made for subjecting renal transplant recipients to regular US of their transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination.
☆Level Of evidence: II
☆Drawbacks of regisrry data
1. Variable quality of the collected data
2. Lack of active follow up(which may undestimate rates of adverse events
3.The intended design does not automatically lead to study of a certain quality.
Please summarise this article
Introduction
Previous studies have investigated cancer incidence in recipients of a specific organ (kidney, liver or cardiothoracic organ), and often focus on a single transplant type, a specific form of malignancy, in a single center, or with limited duration of follow-up
This is the first study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs
Materials and Methods
All patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant (between 1 January 1980 and 31 December 2007)
Combined heart and double lung transplant were regarded as lung transplant recipients. Combined pancreas and kidney transplant were classed as kidney recipients
Exclusions were pancreatic transplant alone and all other multi-organ transplant recipients
The study consists of 37 617 transplanted patients with known age and gender at transplantation. Follow- up of patients was from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death
The median follow up period was 16 years
Results
Total Of 37617 transplanted patients were included (67% received a kidney or simultaneous kidney and pancreas, 18% a liver, 10% a heart and 5% a lung or heart/lung)
15% developed a cancer [the first cancer was NMSC (3276 patients)]
The 10-year incidence of de novo cancer in transplant recipients is over twice that of the general population
NMSC is much more common (over 14 times that of the general population)
The SIR are particularly high for nonmelanoma skin cancer, cancer of the lip, PTLD and anal cancer, but the incidence of different types of malignancy differs according to the organ transplanted
The incidence of NMSC in kidney transplant recipients was unaffected by the type of immunosuppression medication
Discussion
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients (which is three times higher than that for liver recipients)
No increase risk of breast cancer
Weakness of the study: the lack of complete data on immunosuppression. Induction and maintenance immunosuppressant is different from organ to organ (Heart transplant recipients have generally received biological agents such as antithymocyte globulin for induction with higher levels of calcineurin inhibitor (CNI) based triple therapy whereas in liver recipients receive a lower immunosuppressive burden using protocols, which involve tapering to CNI monotherapy (usually tacrolimus) in all but autoimmune liver disease
What is the level of evidence provided by this article?
Retrospective cohort study (level II)
What are the drawbacks when we use the registry data?
1. incomplete recording
2. reporting of cancers may not be complete
3. lack of complete data on immunosuppression
4. loss of follow-up
5. different protocol of immunosuppressions
This study depended on linked data between UK Transplant Registry and cancer registrations following solid organ transplantation in England , Wales and Scotland. This study cohort consists of 37 617 patients transplanted who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007. A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC (C44), and 2856 patients were registered with a de novo cancer other than a nonmelanoma skin cancer. Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients. NMSC is much more common with a risk of over 14 times that of the general population.
For kidney transplant recipients, the overall incidence rate of cancer in the transplanted population is just over twice that of the general population. The overall standardized incidence ratios are greatest for lung transplant recipients. The incidence of nonmelanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients. Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients. The incidence of oral cancer in liver recipients is also high, but 15 of the 18 observed incidences of oral cancer occurred in those whose primary disease was alcoholic liver disease. The SIR following lung transplantation increases dramatically at first and then declines over time. The pattern is similar for liver recipients, although the SIR is generally lower. For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines, but patterns in the incidence rates of many other malignancies vary between organs.
Following kidney transplantation, the SIR increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach) and decreases for others (Kaposi sarcoma, leukaemia). The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Following liver transplantation, the SIR for several cancers (cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas) peaks within 2 years of transplantation, and then declines steadily. In heart transplant recipients, the SIR for bladder, lung and oral cancer, as well as Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
The pattern is similar following lung transplantation, except there is less evidence of an increase over time in the SIR for leukaemia and lung cancer.
The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females. The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population. For each of the types of cancer shown, the hazard of occurrence is greater in males than females, and increases with increasing age. The risks of developing PTLD and kidney cancer have increased over the study period. Body mass index, and whether or not a patient was on dialysis at time of listing for transplantation, where available, did not significantly affect the hazard of cancer after adjusting for the factors . For recipients of a liver, recipient age group and primary disease affected the risk of skin cancer (p < 0.001 and 0.01, respectively) and colorectal cancer (p = 0.06 and 0.002, respectively). The risk of PTLD only depended on recipient gender (p = 0.02), and the risk of lung cancer depended only on recipient age group (p = 0.02). For recipients of cardiothoracic organs, we only identified a significant dependence of the risk of PTLD on recipient age group for heart recipients (p = 0.004Impact of initial immunosuppression From the available data, the incidence of NMSC in kidney transplant recipients was unaffected by whether azathioprine or MMF was used at three months, nor was it affected by the use of tacrolimus or ciclosporin. For other types of cancer, there was insufficient data for reliable estimates
1. What is the level of evidence provided by this article?
level 2
2. What are the drawbacks when we use the registry data?
some information will be missed and they could be a source of bias (selection, information or confounding)
Objective
In this cohort study they include Data on transplant recipients in the UK Transplant Registry, and the separate registries for Wales and Scotland, using the NHS number. The data selected between 1 January 1980 and 31 December 2007
Methods
In this cohort they use the Standardized Incidence Ratio (SIR). This is the ratio of the observed number of new cases of malignancy in the study cohort to the expected number in the general population.
Results :
The cumulative incidence rate of cancer in the transplanted population is just over twice that of the general population. And further increasing with increasing the duration of transplantation The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma
he incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 folds higher in recipients of lung or combined heart and lung transplants
Regarding NMSC The is 13 times that of general population
Regarding renal transplant recipients in the current study are NMSC, PTLD, and RCC.
Conclusion
Malignancy is more frequent in solid organ transplantation and its frequency depends on many factors including the organ transplanted and type pf malignancy
level of evidence
II
What are the drawbacks when we use the registry data?
Additional work for data collection – Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders
– Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission
– Target population depends on external validity (participating healthcare special disciplines) – Non-homogeneous definition and scope of international registry items
– Complex data privacy issues
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization
Please summarise this article
Summary:
-An increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
-It is the first detailed registry study of cancer occurrence in British transplant recipients which shown evidence of different patterns of cancer occurrence in recipients of different organ types. The overall incidence of cancer (excluding
NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population , and over three times higher in recipients of lung or combined heart and lung transplants .
– It is cohort study consists of 37 617 transplanted patients with known age and
gender at transplantation. Patients were followed up from the date of first
transplant to the earliest of the date of first reported de novo malignancy,
or date of death within the study period.
-NMSC is the most common malignancy for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients.
– Liver recipients appear to be relatively protected against cancer of the lip and anal canal, diseases which, like NMSC, which may reflect lower doses of maintenance immunosuppression, in particular avoidance of azathioprine and the absence of biological induction agents in UK liver transplant immunosuppressive protocols.
-They have found higher rates of non-Hodgkin’s lymphoma compared to Sweden, Finland and Canada, and the high rate of kidney cancer seen in Canada and Australia, but not to such an extent in Sweden, is similar to
the UK.
-There is no high rates of hepatobiliary, pancreatic, prostate, kidney, uterine and
cervical cancer in the UK.
-Some diseases for which transplantation is undertaken may be associated with malignancy elsewhere, or may be a marker of exposure to potential carcinogens. For example, Analgesic nephropathy or aristolochia use may necessitate renal transplantation, while being associated with transitional cell carcinoma of
the native urothelium .
-As expected the study shows a very high incidence of posttransplant lymphoma and Kaposi’s sarcoma, much in excess of the incidence of all other cancers with the exception of NMSC.
-The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984, an observation which probably reflects the more aggressive immunosuppressive protocols available today, as well as the development of antimicrobial drugs which has enabled patients to tolerate more aggressive immunosuppression without succumbing to opportunistic infection.
-The other cancer whose incidence is clearly increasing in renal transplant
recipients over the study period is renal cell carcinoma. The reason for this is not clear, but may in part reflect the increasing age of the recipient in whom renalmalignancy is more common and in part the occurrence of cancer in acquired cystic disease of the native kidneys .
-One cancer whose incidence is not increased in the study is breast cancer.
– Another tumor whose incidence might be expected to be higher is cervical carcinoma, since it is known to be a consequence of papilloma virus infection .
–Limitations :Aweakness of the study is the lack of complete data on immunosuppression.
-It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be
recorded.
What is the level of evidence provided by this article?
Level 2
What are the drawbacks when we use the registry data?
-Incomplete and inadequate data collection.
-Incomplete follow- up.
introduction
the incidence of malignancy in post-transplant recipient is higher as compared to general population. Different types of cancers are more common in different types of organ transplantation. this study tried to identify different cancers occurring in various organ transplant patients.
Many studies occurring nationally and internationally has their limitations of small sample size and short follow-up.
this study showed that incidence of malignancy among transplant patients were twice as compared to non-transplant population in UK.
This incidence may vary according to the transplanted organ, however common cancers found are non-melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
the SIR for cancers was higher for lung transplant patients. the incidence
In general, for all transplant recipients, the risk of cancer was higher in males than females and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
However, with all this data, it is still unclear how to manage increased risk of cancer. It is also yet unknown how significant the impact of early cancer detection is on superior cure rates in this immunosuppressed population.
Level of evidence
This is a retrospective cohort study, and hence, level of evidence 2.
What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
a) Variable quality of the data.
b) lost to follow-up on long-term
c) Lack of control group
e) Bias associated with the data collection
f) Underestimation of the prevalence/ incidence rates due to underreporting
Summary
This is a retrospective descriptive study that analysed the incidence of malignancy in solid organ recipients between 1980 and 2007 in the UK data registry. They included recipients who received a first kidney transplant, liver, lung and heart, and excluded pancreas and multi organ recipients. The sample size was large with 37,617participants with 67% of them being kidney transplant recipients.
Overall transplant recipients were twice at risk to develop malignancy in comparison to general population. The immediate post-transplant period (<3years) is associated with high SIR for liver and lung recipients.
Kidney transplant recipients had increased risk for NMSC, lip, Kaposi sarcoma, NHL and anal cancer. Liver transplant recipients had lower risk of NMSC at 6 .0 in comparison to other organ recipients, however they had higher risk of oral cancers. Lung transplant recipients had the highest incidence risk at 3.6, and were at the highest risk of developing NHL.
Factors affecting included gender and increased age for kidney transplant recipients, and age and prior diagnosis for liver transplant recipients; of note the type of immunosuppression did not affect the incidence of NMSC in kidney transplant recipient.
The major strength of the study was that it had a large sample size, however being a descriptive study it was not able to test for any associations. The study was done only in the UK thus may be difficult to generalise to other populations.
Level of evidence 3
Drawbacks when using registry data
Incomplete/ missing data
Lack of active followup
Selection bias
The incidence of de novo malignancy is soaring post transplantation and immunosuppression with most common tumors encountered are non-melanotic skin cancer with incidence levels at 13 times higher than general population. Anal cancer, post-transplant lymphoproliferative disease of either Hodgkin’s lymphoma or non-Hodgkin’s lymphoma variants and lip cancers are the most prevalent types of post transplantation with 10 years incidence rate double the one in general population.
However, the incidence and type of malignancy is variable according to the kind of organ transplantation.
To verify this notion a retrospective observational study was conducted to assess the incidence and type of malignancy commonly linked to each allograft type in a cohort of patients observed from 1980 through 2007, consist of 37617 patients 67% kidney transplant recipient,18% a liver ,10% heart and 5% lung transplant.
Results:
5706 developed cancer of whom 2856 developed non melanoma skin cancer.
After transplantation all patients should undergo regular screening for non melanoma skin cancer particularly lip and anal cancer. That has to be concomitant with life style modification and sun light avoidance.There is no indication to increase screening rate for breast cancer and cervix cancer. In patients with liver transplant , digestive system screening , has to be done regularly. similarly, patients with primary biliary sclerosis , should have regular colonoscopy screening.Kidney transplant recipient must have an ultra sound screening of native kidneys for malignancies particularly in those with analgesic nephropathy and Aristolochia-related interstitial nephritis as its indicative to assess cystoscopically the urothelium.
Level of evidence :
of registry based study is 3 , as its retrospective study in general.
Draw backs of registry data studies :
1) the level of data is not consistent through out the cases registered
2) the criteria for diagnosis is not standardized.
3) No follow up data and no confirmatory information
4) No control population.
5) collection is influenced by other parties
aim:
Kidney transplant recipients have a higher rate of malignancies, so this study examined and compared the rates after different organ transplants.
methods and materials:
This study included data from 10 cancer registries (8 from England, 1 from Wales, and 1 from Scotland) from 1980 to 2007. 37,617 first-time kidney, liver, heart, or lung transplant recipients were included.
All patients transplanted in England, Wales, and Scotland between 1 January 1980 and 31 December 2007 who got their first kidney, liver, heart, or lung transplant and had an NHS number are included in the study cohort.
To code new malignancies, the Cancer Registries utilize histology and other vital information, such as cross-sectional imaging.
To exclude cancers that may have been prevalent at the time of transplantation, all patients diagnosed with cancer within one month of transplant were excluded, with the exception of 620 patients diagnosed with posttransplant lymphoproliferative disease (PTLD).
results :
– The median follow-up time for this sample was 16 years,5706 patients (15%) developed cancer.
– 3276 patients developed NMSC after transplantation.
– 2856 patients had de novo cancers other than non-melanoma skin cancers.
– Receivers have a 90 per thousand incidence rate 10 years after transplantation.
– Two years after transplantation, this relative risk remains constant. NMSC is substantially more common, and the standardized incidence was 14.4, implying transplant recipients had over 14 times the risk of this kind of cancer.
– Nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma have high SIRs.
– Lung transplants have the highest SIR.
– Liver transplant recipients have lower rates of non-melanoma skin cancer and lip cancer.
– Non-lymphoma Hodgkin’s SIRs peak one year after transplantation and thereafter fall for all organs.
limitations:
strength:
– follow up may be lost in long term
– underreporting leads to underestimation
– bias due to heterogeneity of data
Summary:
This study compares the incidence of de novo malignancy in solid organ transplant recipients with general population using the Standardized Incidence Ratio (SIR). It is an observational longitudinal cohort study and includes all UK transplant patients (NHSBT data) from 1980 to 2007, but patients with diagnosis of cancer within one month post-transplant were excluded. The median follow up period of this study was 16 years. The 10-year incidence of de novo malignancy in post-transplant patients was twice that of general population with non-melanoma skin cancer being the commonest. Other common cancers were cancer of the lip, Kaposi sarcoma, PTLD, anal cancer and kidney cancer.
Level of evidence: Level 2
What are the drawbacks when we use the registry data?
Lack of follow-up
Limited amount of data
Selection bias.
I like your analysis of level of evidence, limitations of this study.
I like your analysis of level of evidence and drawbacks of this study.
Q1: Is it a longitudinal study or a cross sectional study?
A 2: It is a longitudinal study.
Q2: We know that it is a longitudinal study. Is it a cohort study or case control study?
A 3: Case-control studies are always retrospective, we find out the end-point (ESRD, death, DM or HT in donors) and one looks back for underlying factors. While in cohort studies (that is either prospective or retrospective) we start with risk factors and follow these patients to look for the end-point (primary, co-primary and secondary).
Conclusion: This is an observational longitudinal cohort study
Please summaries this article
Aim of the study: (UK registry audit) Compare incidence of de novo malignancy in solid organ transplant with general population and compere these incidences with different organs in the British population.
Type of study: retrospective observational case control study
Population:
Inclusion: All UK transplant (NHSBT data) from 1980 to end of 2007.
Exclusion: Pancreas alone and all other multi-organ transplant recipients. All patients with cancer diagnosis within one month of transplant were excluded, those with PTLD diagnosis.
Exposure: patient who had solid organ transplant
Control: general population
Outcome: Cancer incidence in the transplant population was compared with the general UK population using the Standardized Incidence Ratio (SIR).
Method: NHSBT data were linked with data made available by the cancer registries in England, Scotland and Wales. Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
Analysis: adjusting for confounders: age group and gender, primary disease, smoking history, obesity, dialysis
Results:
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years). The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer (NMSC) being 13 times greater than general population for all organs.
Most common cancers: NMSC (17), cancer of the lip (66), Kaposi sarcoma (17), PTLD (7-12) and anal cancer (10), kidney (8) have the largest SIRS. (Fractions removed to nearest number, figures for kidney Tx).
Patterns in SIRs over time since transplantation are different for different types of transplant recipient, as well as for different malignancies.
Pattern with time: Non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines (Key figure attached)
Strength:
Excellent study to help counselling the patient before transplant for shared decision making and help stratification therefore increased awareness of cancers. Very big population
Negatives from the autors:
Negatives from my opinion:
Population in the study: They did not adjust for ethnicity which OI believe big drawback specially the UK population is more diverse, and the nonwhite population is growing up. The current British population is changing therefore SIRs (either transplant and general) may have changed. (REF below)
Accessed 25 Jan
http://hummedia.manchester.ac.uk/institutes/code/briefings/dynamicsofdiversity/how-has-ethnic-diversity-grown-1991-2001-2011.pdf
What is the level of evidence provided by this article?
Retrospective case control study (middle of the pyramid)
What are the drawbacks when we use the registry data?
Lack of information and difficult to find proper control
Is it really case control study?
However, I like your long list of limitations and strengths of this study.
1. Please summarise this article
Results
Total new cancer incidence (excluding nonmelanoma skin cancer):
Time trends following transplantation
==========================
2. What is the level of evidence provided by this article?
==========================
3. What are the drawbacks when we use the registry data?
The limitations of registries include:
This is an inadvertent duplication of your reply.
1. Please summarise this article
Results
Time trends following transplantation
==========================
2. What is the level of evidence provided by this article?
==========================
3. What are the drawbacks when we use the registry data?
The limitations of registries include:
I do not agree with your equivocal stance on level of evidence 2 or 3!
However, I like your list of limitations and strengths of this registry-based study.
Summary of the article
COMPARISON OF THE INCIDENCE OF MALIGNANCY IN RECIPIENTS OF DIFFERENT TYPES OF ORGAN: A UK REGISTRY AUDIT
This retrospective review article, using UK transplant registry in the period between Jan1980 and Dec2007, studied the incidence of malignancy in allograft recipients post-transplantation in comparison to the general population with matching for age, gender and time period. The 10 yrs incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of nonmelanoma skin cancer(NMSC) being 13 times greater. NMSC, cancer of the lip, PTLD and anal cancer have the largest standardized incidence ratios.
Study’s results
• The overall incidence rate of cancer, 10 yrs post-transplant is 90 per 1000 patients which is more than twice the rate in the general population.
• NMSC is much more common, and the corresponding standardized incidence was 14.4. NMSC is over 14 times that of the general population.
• The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
• Non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic transplant recipients.
• The incidence of post-transplant lymphoma in kidney recipients has increased ninefold since 1980– 1984. This observation probably reflects the more aggressive immunosuppressive protocols available today.
• The incidence rate for breast cancer is not increased in this study, for unclear reason.
• The incidence rate of cervical cancer is not increased which may be explained by the active cervical screening program in the UK.
The level of evidence provided by this article?
This is retrospective study, with level of evidence grade 3.
What are the drawbacks when we use the registry data?
Registry Disadvantages:
• Disease-specific, not longitudinal. limited amount of data for every patient.
• Does not include information necessary for billing.
• Requires hardware, software, and maintenance.
• Requires data entry and data maintenance.
• Parallel documentation system (i.e., some information has to be entered in two systems).
• Can’t stand alone, must have an additional documentation system.
Registry Advantages:
• Flowsheet is a powerful tool to monitor clinical data and track trends.
• Provides a dashboard of who needs what.
• Provides total population data reporting with no chart abstraction.
• Generates revenue (it shows when services are needed).
• Provides outreach information at fingertips.
• Improves team-based care.
• Smaller software package than EHRs.
..
I do not like your analysis of level of evidence. However, I appreciate a long list of limitations and strengths of this registry-based study.
Summarise of this article
the aim of this study to know the risks of developing denovo malignancy and compare it with the general pop[ulation. Adding to that, link the type of cancer developed after each type of solid organ transplantation.
They found an increased number of malignancies 12 times after transplantation compared to the general population.In specific, non-melanoma skin cancer had a higher incidence among transplant recipients, a staggering 13 times higher. This incidence may vary according to the transplanted organ, however common cancers found are non-melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
The data were collected from UK registry system, adding to the data registered in cancer centers in Englan , Wels and Scotland.
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL).
The immunosuppression used in the transplant was not properly linked to the type of cancer and was incomplete data and this create sort of bias.
level 2
Please use bold or underline for heading or sub-headings.
I like your analysis of level of evidence, limitations of this study.
Introduction
Incidence of malignancy among organ transplant recipient are high in comparison to general population and there’s variations in incidence of malignancy with different types of malignancy and associated with different types of organ transplant.
This study done to understand risk factors and identify type of cancer related to specific organ transplant for screening and surveillance in post operative periods.
There’s many studies national and international to identify risk but all of them have bias if underestimation due to small sample and short fallow up.
Methods and Materials:
This cohort study done between 1 January 1980 and 31 December 2007, and how have NHS number, data collected from transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant (NHSBT), and linked with cancer information post transplant registration from different countries.
The information of malignancy was obtained from age, gender, time of cancer occurrence but excluded cancer which prevalent at time of transplant or after one month post transplant except lymph proliferation malignancy ( Hodgkin and non Hodgkin’s lymphoma ), histology of malignancy and date of death.
History of smoking and obesity with body mass index was obtained and primary cause of kidney failure and duration of dialysis was collected.
Results:
The incidence of cancer post transplant is low between 1980–1984 because unrecorded of cases at that time.
The median follow up period for this cohort of patients was 16 years.
However, from the total transplant patients only 15% developing cancer.
The incidence of cancer in the transplanted population is double of the general population.
The incidence ratios are high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
Incidence of nonmelanoma skin cancer is much less in liver transplantation.
Lymphoma rates are similar in kidney and liver transplant except non-Hodgkin’s lymphoma incidence is high in cardio thoracic transplant.
For all organ transplant the incidence of non-Hodgkin’s lymphoma is increased in first year post transplant and then decline after that.
For kidney transplant increase in incidence of non melanoma skin cancer and anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach and decreases for Kaposi sarcoma, leukaemia.
For liver and ovarian cancer increase in the years immediately post transplantation and then decline, while breast, pancreas and uterine cancer remain constant.
For liver transplantation, the cervix, colorectal, Hodgkin’s lymphoma, liver, multiple myeloma and pancreas peaks within 2 years of transplantation, and then declines steadily.
In heart transplant recipients, the bladder, lung and oral cancer, and Hodgkin’s lymphoma, increase over time, whereas those for most other cancers remain stable or decrease.
For lung transplantation; there is less evidence of an increase of leukaemia and lung cancer with time.
Incidence of cancer more in males than females and age groups above 50years in comparison to general population.
There’s insufficient data regarding obesity and use of immunosuppressive therapy in reduce evidence of cancer post transplant.
Discussion:
Non melanoma skin cancer is the most common malignancy in kidney transplant.
The incidence of posttransplant lymphoma in kidney recipients has increased ninefold since 1980– 1984.
However, This registration not differentiate between native kidney cancer or from transplant organ. There’s no sufficient data on use of immunosuppressive therapy in developing cancer.
This study concluded for counselling pretransplant patients on the risk of malignancy and should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure.
However, there is no need for any additional breast or cervical cancer screening.
Level 2
I like your analysis of level of evidence, limitations and strengths of this study.
Summary
This article focusses on the development of de novo malignancy in transplant recipients and the comparison with incidence of the same among different organ transplants across the UK.
The study found that incidence of malignancy among transplant recipients is twice the rate compared to incidence among the general population. In specific, non melanoma skin cancer had a higher incidence among transplant recipients, a staggering 13 times higher. This incidence may vary according to the transplanted organ, however common cancers found are non melanoma skin cancer, cancer of the lip, PTLD, and anal cancer.
The data used in this study was obtained from two major sources – the UK transplant registry, and cancer registries across England, Wales, and Scotland, regarding cancer among transplant recipients post transplant. The data included kidney, liver, heart, lung transplant, and combined pancreatic-kidney transplants. The majority were kidney transplants, at 67%, followed by liver at 10%.
Immunosuppressive drugs used for the recipients included in the study were Azathiprine, MMF, tacrolimus, and cyclosporin. The data was available only for half of the patients, and only at 3 months post transplant. SAS or statistical analysis software was used for calculations. Comparisons were made based on Cox regression models and adjusted for recipient age group, gender, primary disease, and year of transplant.
The study found that SIR for cancers was greatest for lung transplant recipients, with incidence of non-melanoma skin cancer and cancer of the lip being least for liver transplant recipients (These patients had less than half of the risk for these cancers compared to recipients of other organs such as kidney and lung.) Heart transplant recipients had the greatest incidence of Non-Hodgkin’s lymphoma (NHL).
Different factors appeared to affect the incidence of various cancers among these transplant recipients. In general, for all transplant recipients, the risk of cancer was higher in males than females, and increased with age. In specific, risk of PTLD and kidney cancer increase with time.
Incidentally, BMI and prior dialysis did not have a significant effect on cancer incidence in these patients.
Liver transplant recipients were found to be at a higher risk of skin cancer with increasing recipient age and colorectal cancer with history of primary disease.
Lung cancer was highly impacted by recipient age, with PTLD dependent on recipient gender.
Regular ultrasounds, surveillance of aerodigestive tract, and colonoscopy can be done for transplant recipients, to detect changes in favor of liver, lung, colon, kidney, or anal cancer. How helpful this is toward long term outcome is yet to be seen.
However, with all this data, it is still unclear how to manage increased risk of cancer. It is also yet unknown how significant the impact of early cancer detection is on superior cure rates in this immunosuppressed population.
Level of evidence
This is a retrospective cohort study, and hence, level of evidence 2.
Drawbacks
Incomplete data – most importantly for immunosuppressive regimen which forms an important part in cancer incidence in transplant recipients. Selection bias
Please use bold or underline for sub-headings in your summary.
I like your analysis of level of evidence, drawbacks and strengths of this study.
This study recruits data between 01st Jan 1980 and 31st Dec 2007 from Britain registry comprising 37 617 transplanted patients and highlights the incidence of De-novo cancer in solid-organ-transplant recipients in comparison to age and gender matched general population . Counseling about the increase chances of malignancies post-transplant due to immunosuppressive medications, and development of screening and surveillance program for early detection.
The study stated that 5706 patients (15%) developed cancer in the median follow up period of 16 years and the most common malignancy which occur post-transplant is NMSC , occurring with a frequency of 14 times more compared to general population .The malignancies which occur two times more are those occurring in renal, heart and liver transplant recipients ,however, chances of malignancy are low in liver transplant recipients due to minimum doses of immunosuppression and no induction therapy being used. PTLD occur with increased frequency in the first year following transplantation , with NHL having greater chances of occurrence in cardiothoracic transplant recipients. Male population especially younger group had more chances of cancer but BMI and dialysis have no effect. No increased risk of leukemias ,breast, uterine, ovarian, and prostate cancer are observed in post-transplant patients.
Level of evidence
This is a retrospective cohort level of evidence II
What are the drawbacks when we use the registry data?
No data available on immunosuppression protocol.
Comparison group was not properly selected.
No active follow up done
No validity and generalisabilty of the results.
Why do you think that the comparison group (control) was not properly selected? WHat is your suggestion?
Introduction:
An increased risk of developing cancer is an established complication associated with immunosuppression.
Numerous studies have investigated cancer incidents after transplantation.
Materials and methods:
This cohort study consists of all patients transplanted in England, Wales and Scotland.
The cancer registries code any new malignancy on the basis of available histology and other information.
All patients with cancer diagnosis within one month of transplant were excluded.
Statistical methods:
Cancer incidents incidence in transplant population was compared with general people in UK using standerdized incidence ratio
Registration of newly diagnosed cancers in England were obtained from office for national statistics.
Data on immunosuppression was obtained at 3 months following transplantation.
Results:
Of the 37617 transplanted patients, 25105 (67%) received a kidney transplant, 18% liver, 10% heart and 5% lung . The median follow up period was 16 years.
A total of about 5704 (15%) developed a cancer in this period.
NMSC is much more common with the standardized incidence was 14.4%.
The overall incidence rate of cancer in the transplanted population is just twice that of general population.
The overall SIR is greatest for lung transplant recipients. The incidence of nonmelanoma skin cancers is much less in liver recipients and the SIR for cancer of the lip in this patients is less. Lymphoma rates are similar except that non Hodgkins lyphoma has a greater incidence in cardiothoracic transplant.
.
Please use bold or underline for heading or sub-headings.
What are the level of evidence, limitations and strengths of this study?
Kidney transplant recipients have increased incidence of malignancies, The study was done with the aim of evaluating the malignancy incidence in transplant recipients and compare the incidence following different organ transplants.
This was a retrospective study involving data from 10 cancer registries (8 from England and 1 each from Wales and Scotland) for a period of 28 years (1980 to 2007) was done. The cohort included 37,617 transplant recipients who received a first kidney, liver, heart, or lung transplant. Multiorgan transplant, pancreas transplant recipients and those with cancer diagnosed within 30 days of transplant (except post-transplant lymphoproliferative disease – PTLD) were excluded from the study. Cancer incidence in the cohort was compared with the general population of UK using the Standardized Incidence Ratio (SIR).
Results:
67% of the study population received a kidney transplant while liver, heart and lung transplant recipients comprised 18%, 10% and 5% of the study population respectively. Median follow-up was 16 years. 15% of the patients developed cancer during the study period. Cancer incidence rate was double in heart, kidney or liver transplant, and 3 times in lung or combined heart-lung transplant. Cancer incidence rate at 10 years post-transplant was more than double as compared to 10-year incidence rate of cancer in general population of England (9% versus 3.6%). The SIR were high for non-melanoma skin cancer (NMSC), Lip cancer and Kaposi sarcoma (16.6, 65.6, and 17.1 respectively).
SIR is greatest for lung transplant recipients. In liver transplant, the NMSC SIR is less and lip cancer SIR is also less than half of that in other transplants while oral cancer SIR is high at 10, especially in those with alcoholic liver disease. The SIR of non-Hodgkin’s Lymphoma (NHL) is high in cardiothoracic transplant. Pancreas, uterus and bladder cancer have constant SIRs.
Factors affecting time to cancer diagnosis include male gender and increased age. SIRs for each cancer decrease with increasing age. Incidence of NMSC in kidney transplant was not affected by use of tacrolimus or cyclosporine, or azathioprine or MMF use. NHL rates were higher in UK than in Sweden, Finland, or Canada.
Weaknesses: Lack of complete data on immunosuppression and likely underestimation of cancer incidence rates due to inclusion of first cancer occurrence only in the study.
Recommendations: Counselling and screening for NMSC, lip and anal cancer in all solid organ transplant recipients. Screen for aerodigestive tract, hepatocellular carcinoma (in cirrhosis), and colonoscopy in primary sclerosing cholangitis in liver transplant patients. For kidney transplant recipients, regular ultrasound for renal cell carcinoma in acquired cystic kidney disease, and cystoscopy for analgesic nephropathy or aristolochia related interstitial nephritis is recommended.
2. What is the level of evidence provided by this article?
Level of evidence: Level 2 – retrospective cohort study
3. What are the drawbacks when we use the registry data?
Registry data has certain inherent drawbacks. These include:
a) Variable quality of the data.
b) Participants lost to follow-up on long-term
c) Change in classification/ diagnostic parameters over time, leading to difficulty in standardizing the data at time of analysis.
d) Lack of control group
e) Bias associated with the data collection
f) Underestimation of the prevalence/ incidence rates due to underreporting
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.
Introduction
There is an increased frequency of newly diagnosed cancers after organ transplantation. It is crucial to recognize the increased risk and tell the patient before transplantation in order to formulate a rational strategy for screening and surveillance in the postoperative period.
The objective of the study was to compare the incidence of newly diagnosed cancer to that of the general population. Additionally, the incidence of malignancy following transplants of solid organs was compared.
Methodology
From 1980 through 2007, all transplants of solid organs from the United Kingdom, Wales, and Scotland were included. Heart and lung transplants are classified as lung transplants, whereas pancreas and kidney transplants are classified as kidney transplants.
Results
· NMSC is the most prevalent complication after kidney transplant, occurring 14 times more frequently than in the matched UK general population.
In all transplanted organs, the incidence of additional malignancies was two times that of the general population, and it was significantly greater in lung and heart transplant patients.
Lower malignancy rates in liver transplant recipients may be attributable to the Uprotocol’s lack of induction treatment and lower immunosuppressive dosage.
In the first year following transplantation, PTLD prevalence was higher, and non-lymphoma Hodgkin’s was more prevalent in cardiothoracic transplants.
Other than NMSC and PTLD, the incidence of malignancies in recipients older than 50 is comparable to that of the general population.
· Younger age at transplant and men are associated with an increased risk of cancer, however BMI and dialysis do not raise the risk of cancer.
Leukemias and breast, uterine, ovarian, prostate, and pancreatic cancers occur with the same frequency in organ recipients as in the general population.
Conclusion
This study identifies patient groups and cancer types, contributes to the development of a surveillance program, and provides information for counseling pretransplant patients about the risk of cancer. All transplant patients should be checked routinely for NMSC, oral, and anal malignancies, in addition to adopting a sun-safe lifestyle.
Regular renal ultrasound for kidney allografts and native kidneys for tumors is especially important for those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis, which also require cystoscopic evaluation.
Level of evidence
This is a retrospective cohort level of evidence II
What are the drawbacks when we use the registry data?
Voluntary reporting may underestimate the incidence rate. It may be obtained from different countries, which may bias it due to reference population decline.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations of this study. yes, under-reporting may be an issue here.
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit
· Summarise the article
o Introduction
The increased risk of malignancy is a well-recognized complication among organ transplant recipients on immunosuppressive therapy.
o Study objectives
To describe the incidence of de novo malignancies in transplant recipients and to compare these incidences in different types of organ transplant.
o Methods
A retrospective cohort study of 37,617 transplanted patients who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007 in England, Wales and Scotland. Patients were followed up from the date of 1st transplant to date of 1st reported de novo malignancy, or date of death within the study period. Pancreas transplant recipients and other multi-organ transplant recipients (except heart-lung and pancreas-kidney) were excluded.
o Results
-Fifteen percent (5706 patients) developed cancer within the study period.
-NMSC was registered as the 1st cancer in 3276 patients; among these patients, 426 developed a different de novo cancer.
-A total of 2856 patients were noted to have a de novo cancer other than a NMSC.
-The 10-year incidence of de novo cancer was two times greater in transplant recipients compared to the general population.
-The overall incidence of cancer in transplant recipients was twice that of the general population.
-The incidence of NMSC was almost 14 times greater that of the general population.
-The incidence of different types of malignancy differs with the organ transplanted.
-NMSC, lip cancer, KS, PTLD and anal cancers had the highest SIRs.
-NMSC had an SIR of more than 16 times in kidney and cardiothoracic transplant recipients. This was 3 times higher than that of liver transplant recipients.
-Lung transplant recipients had the greatest overall SIR.
-In liver transplant recipients, incidence of NMSC was much less, so was the SIR for lip and anal cancer compared to other organ transplants; however, incidence of oral cancer was high.
-NHL has a greater incidence in cardiothoracic transplant recipients.
-Generally, the SIRs of each cancer decreased with increasing age and were higher in males than females.
-Initial immunosuppression therapy did not affect the incidence of NMSC in kidney transplant recipients.
-The incidence of KS and renal cell carcinoma has increased among kidney transplant recipients.
-Geographical location also had an impact on the incidence rates of many cancers.
-Smoking and underlying viral infections can increase risk of developing malignancies.
o Weakness
-Incomplete data on immunosuppressive therapy
-Underreporting of cases
-Censoring of recipients at the 1st occurrence of any malignancy (except NMSC)
-Different induction therapies for different organ transplants
o Conclusion
NMSC is the most common malignancy, hence all transplant recipients should be screened regularly for NMSC, including lip and anal cancer. Lifestyle changes to reduce sun exposure should be emphasized.
·What is the level of evidence provided by this article?
Level II – retrospective cohort study
·What are the drawbacks when we use the registry data?
-Lack of data verification
-Incomplete data
-Underreporting/ underestimation of cases
-Selection bias
-Variable quality of data
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
Strengths:-
-a large volume of data
-the data in this UK Transplant registry has been linked to information on other registries using the NHS number
-it includes a diverse set of study participants
SUMMARISE THE ARTICLE
INTRODUCTION.
Transplantation is associated with immunosuppressive meds with antecedent increased risk of de novo malignancy post transplant. underscoring the above is the need for an appropriate follow up post transplant and improve our outcomes.
STUDY OBJECTIVE.
To establish the incidence rate of de novo malignancies in British Solid Organ Transplant Recipients in comparison to the general population.
METHODOLOGY.
-A retrospective cohort study on 37617 transplant recipient patients transplanted in Wales, England and Scotland between 1st january 1980 and 31st December 2017 and followed up from date of transplant to either 1st denovo malignancy or death during the study period.
-The cancer incidence rates post transplant were compared with those in the general population using Standard Incidence Ratio and appropriately adjusted for gender, time and age.
INCLUSION CRITERIA.
Pts transplanted in England ,Wales and Scotland ho got 1st kidney, liver, heart or lung transplant between 1st jan 1980 to 31st dc 2017.
-Pts with NHS number.
EXCLUSION CRITERIA.
-Pancreas recipients alone.
-Multiorgan transplant recipients.
RESULTS.
-15%[5706] of patients developed a denovo malignancy during the study period.
-Incidence of cancer in transplanted population is x2 that in the general population esp for NMSC, lip and KS.
-NMSC incidence is less in liver transplant recipients and the SIR for lip malignancies less than half compared to other organ transplant recipients.
-NHL has greater incidence in cardiothoracic organ recipients compared to other organ recipients. For all types of recipients, SIR for NHL increases in 1st year then declines while for the other types of malignancies they do have a varied pattern.
-Alcoholic liver disease is strongly linked to oral malignancies in liver transplant recipients.
-Males are more at risk for malignancies post transplant compared to females.
-The incidence of breast and uterine cancer were unaffected by transplantation in comparison to the general population.
-We did not get strong evidence that the the of immunosuppressive medication affected the incidence of NMSC in kidney transplant recipients.
STUDY LIMITATIONS.
-lack of enough data on immunosuppressive medication.
-Inaccurate incidences of skin malignancies due to underreporting possible from excision of some lesions before a histological diagnosis was made.
CONCLUSION.
-Age appropriate screening and follow up post transplant should be done. This cohort of patients should be counselled pre transplant about risk of malignancies post transplant especially NMSC, lip and anal cancer and the importance of screening .Alcoholics undergoing liver transplant should be screened for PSC nd have regular colonoscopies post transplant.
LEVEL OF EVIDENCE
2 – Retrospective cohort study.
DRAWBACK OF REGISTRY.
-No standard tool to ensure quality of results across the different studies.
-Missing data
-No uniformity in study designs of chosen RCTs.
That is an excellent summary and very well structured reply.
Yes, lack of information on immunosuppression is a key limitation
· Summary
o Denovo cancer in transplant patients is a well-known complication with greater morbidity and mortality.
o Skin cancer (melanoma and none melanoma), lip and ana cancer, PTLD are among most common types.
o The site of organ transplantation (lung, liver, kidney, etc…) is associated with variable incidence of cancer among transplant patients.
o The higher incidence of cancer among transplant patients is expressed as standardized incidence ratio (SIR) which represents the ratio between the observed and expected cancer cases.
o Increased incidence of cancer is related to cumulative effect of immunosuppression rather than being related to a particular drug.
o The cardiothoracic (lung with or without heart) transplant recipients have the highest incidence of none melanoma skin cancer due to use of aggressive immunosuppressive therapy (including induction therapy and TAC based triple immunosuppressive therapy).
o while liver transplantation has the lowest incidence (due to none-use of induction therapy and azathioprine in maintenance immunosuppressive therapy in liver transplantation.
o Lymphoma also is higher among lung transplant recipients.
o The incidence of cancer also varies between different locations that may be attributed to associated risk factors as ethnicity and personal variations as smoking and dietary habits.
o In addition, the original disease (reason for transplantation) may have a role:
§ Smoking which leads to lung damage and lung transplantation (it itself increases risk of lung cancer).
§ Sclerosing cholangitis requiring liver transplantation is associated with colitis and cancer colon.
§ Analgesic nephropathy requiring kidney transplantation and also it increases the risk of urothelial carcinoma.
o Among kidney transplant recipients, none melanoma skin cancer, Kaposi sarcoma, PTLD and renal cell carcinoma are increasing in incidence in last few years that may be attributed to aggressive immunosuppressive therapy (and use of suppressive anti-microbial therapy that prevent opportunistic infections and make our patients tolerating stronger immunosuppressants).
o Renal cell carcinoma may be related to acquired cystic kidney disease due to aging of the recipient (develop cancer in the aging native kidney).
o Screening and surveillance programs should consider the site of organ transplantation and the risky site screening as colonoscopy for cancer colon in case of sclerosing cholangitis, frequent cystoscopy for those transplanted for analgesic nephropathy and regular US for hepatocellular carcinoma in cirrhotic patients.
o Early detection and treatment of cancer improve the patient outcomes.
· Level of evidence: II (retrospective cohort study)
· Drawbacks of registry data:
o It depends on voluntary reporting of cancer so actually it underestimates the cancer incidence.
o Large proportion of missing data (none reported cases) as 17 % of UK transplant cases as in the current study.
o As regard skin cancer registration: many lesions are being excised with histological analysis and confirmation of malignancy plus missing data about basal cell carcinoma.
o Sometimes, incomplete data and lacking details that may be so important as type of immunosuppressive therapy used in each patient and site of origin of renal cell carcinoma either in the graft or the native kidney.
o Lack of documentation of associated risk factors as concomitant diseases or any personal habits that may increase the cancer risk.
o In case of 2nd cancer, only the 1st even is documented (that underestimates the cancer incidence).
o Missing follow up data an final outcomes.
That is an excellent summary and very well structured reply.
Yes missing data is a problem here.
Comparison of the incidence of malignancy in Recipients of different types 0f Organ:
A UK Registry Audit:
Introduction:
The screening of post transplant cancer is as important as education of the recipients about the risk of developing cancer post transplant, inorder to understand the increasing risk and to plan measures to reduce this risk.
This is UK registry is the first registry that study the risk of cancer in diffrent organ post transplantation
Results:
Discussion:
Weaknesses in this study:
Level of evdence:
Cohort (II).
Drawback when use a registry data:
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations and strengths of this study.What are strengths of this study?
Please summarise this article
Introduction:
The risk of malignancy is increased in organ transplant population.
Aim of the study:
-Evaluate the incidence of de novo malignancy in British SOT recipients of different organs
-Compare it with incidence rates in the general population.
Materials and Methods:
– Using data on all transplant recipients in the UK Transplant Registry, held by NHSBT, has been linked to information on cancer registrations following SOT recorded in England, Wales and Scotland.
– Study period: between 1 January 1980 and 31 December 2007.
– All patients with cancer diagnosis within one month of transplant were excluded, except for patients diagnosed with PTLD.
– Patients were followed up from the date of first transplant to the earliest of the date of first reported de novo malignancy, or date of death within the study period.
– Standardized Incidence Ratio SIR used to compare cancer incidence in the transplant population with matched general UK population.
Results
-The cohort consists of 37617 transplanted patients.
– The median follow up period was 16 years
– The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population.
– NMSC is more common over 14 times that of the general population.
– The SIR is high for NMSC, cancer of the lip, PTLD and anal cancer, but the incidence differs according to the organ transplanted.
– Patterns in SIR over time since transplantation are different for different types of transplant recipient,
as well as for different malignancies.
-The general pattern is that the SIRs for each cancer decrease with increasing age, and many of the rates are higher for males than females.
-The incidence of cancers other than NMSC and PTLD in recipients aged over 50 is not much greater than that of the general population.
Limitations:
– No sufficient data on immunosuppression.
– The cancer incidence rates in this study are underestimates, since the study has censored a recipient
at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
Implications:
– National screening program.
– Patients counseling.
What is the level of evidence provided by this article?
level 2 evidence; observational longitudinal cohort study with population data as controls.
What are the drawbacks when we use the registry data?
-The intended design does not automatically lead to a study of a certain quality.
-Variable quality of the collected data.
– No specific tool exists for assessing the quality of a registry-based study
– Need for external and internal validation of collected data
– Possible influence of confounders.
– Absent of complete data.
– Additional work for data collection.
– Lack of control group.
– Complete and long-term follow-up remains challenging (which may underestimate rates of adverse events).
– Non-homogeneous definition and scope of international registry items
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization.
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
Introduction :
Complication of organ transplantation and the associated immunosuppression is an increase risk of developing of de novo cancers .
Objectives :
Understanding the increased risk of denovo cancers in transplant patients
To allow a rational approach to screening and surveillance in the postoperative period.
Materials and Methods:
The study cohort consists of all patients transplanted in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number. Those who received a combined heart and double lung transplant (n = 553) were classed as lung transplant recipients, and those who received a combined pancreas and kidney transplant (n = 764) were taken to be kidney recipients.
The small number of recipients of a pancreas alone (n = 33) were excluded, together with all other multi-organ transplant recipients (n = 177).
Results:
The 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years
A total of 5706 patients (15%) developed a cancer in this period.
In 3276 patients the first cancer registered following transplantation was a NMSC (C44), and of these 426 were subsequently registered as having developed a different de novo cancer.
The 2856 patients were registered with a de novo cancer other than a non melanoma skin cancer
Ten years after transplantation, recipients have an overall incidence rate of 90 per thousand patients
This overall relative risk is more or less constant from two years after transplantation. NMSC is much more common, and the corresponding standardized incidence was 14.4 (95% confidence interval: 13.8–15.0), meaning that the risk of this type of cancer occurring in a transplant recipient is over 14 times that of the general population
The standardized incidence ratios are particularly high for nonmelanoma skin cancer, cancer of the lip and Kaposi sarcoma.
The overall SIR is greatest for lung transplant recipients
The incidence of non melanoma skin cancer is much less in liver recipients and the SIR for cancer of the lip in these patients is less than half that for other transplant recipients
For all organs, the SIR for non-Hodgkin’s lymphoma increases to a maximum at one year after transplantation and then declines.
weakness of the study:
The lack of complete data on immunosuppression.
Conclusion :
The overall incidence of cancer (excluding NMSC), in recipients of a heart, kidney or liver, is over twice that of the general population (SIRs: 2.5, 2.4, 2.2, respectively), and over three times higher in recipients of lung or combined heart and lung transplants (SIR 3.6).
NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients, which is three times higher than that for liver recipients
Level : 11 cohort study
Drawback:’
Disadvantage or inconvenience .the negative parts of situation
That is an excellent summary and very well structured reply.
I like your analysis of level of evidence, limitations of this study.What are strengths of this study?
-The study assessed the SIR of de novo malignancies after transplantation in Britain between 1984 and 2007.
-The overall incidence rate of cancer in the transplanted population is just over twice that of the general population.
-The overall incidence is much higher after lung transplantation compared to other oragn transplantation.
-Among kidney tx:- SIR of NMSC is 16.6 and 2.4 for other malignancies.
-The incidence of NMSC was not affected by the type of IS.
-The SIR for malignancies decreases with age and in patients aged
>50 y, tumors other than NMSC and PTLD is not much greater in
comparison to general population.
-The SIR of NHL increases to peak at 1-year post transplantation then decreases.
-The SIR for malignancies after kidney and hear TX quickly double the general population while after lung or liver TX increases dramatically in the first year then decreases dramatically.
-In general, HR of malignancies increases with age and in males after organ transplantation.
1- A retrospective study with inherent selection bias
2- Heterogenecity of data, different sources(countries) and outcomes
3- lack of immunosuppression data.
4- The cancer incidence is underestimated, as it censored only first event. Thus, developing other cancers was not reported.
I like your analysis of level of evidence of this study.
What are strengths of this study?
1- it is the first detailed registry study describing the cancer occurrence after SOT in UK
2- Data provided helps in designing a follow-up regimen for cancer surveillance after different types of SOT
Please summarise this article
There is higher incidence of denovo cancer post organ transplantation. It is important to understand the increased risk and inform the patient before transplant so that a rational approach can be formed for screening and surveillance in the postoperative period.
The purpose of the study was to compare the incidence of denovo cancer with incidence in general population. Also comparison was done on incidence of cancer following different solid organ transplants.
Methodology
All solid organ transplants were included from 1980 to 2007 from UK , Wales and Scotland. Combined heart and lung transplant- considered as lungs transplant , while pancreas and kidney transplant as kidney transplant.
Results
The cancer incidence was twice than general population after kidney , heart and liver transplants. It was three times higher in those having lung transplants.
The incidence of NMSC was 13 times higher than general population.
The incidence of breast cancer is not increased after kidney transplant. The most common malignancies after renal transplant are PTLD, NMSC, RCC , lip and anal cancers. The incidence of cervical cancer is the same as general population. The incidence of NMSC is 13 times higher . The incidence of lip and oral cancer is less following liver transplant.
What is the level of evidence provided by this article?
Cohort study level 11
What are the drawbacks when we use the registry data?
Data from multiple sources and countries
There can be selection bias
Incomplete data
Incomplete or loss to follow up
Potential outcomes maybe lacking
I like your analysis of level of evidence of this study.
What are strengths of this study?
Summary:
Aim of the study:
To evaluate the incidence of de-novo cancer in the general population and solid organ transplant recipients and to compare the incidence of de-novo cancers among different organ transplantation.
Methodology:
This is a retrospective cohort study for all solid organ transplant recipients obtain data from cancer registries in England, Wales and Scotland.
In this study standardized Incidence Ratios matched for age, gender and time period were used to compare de-novo malignancy in solid organ transplant recipients with general population.
Result:
Among 37617 transplanted patients 67% kidney, 18% liver, 10% heart, and 5% of lung transplant. Median follow up was 16 years.
15% patients develop cancer in this time frame.
3276 patients got first time cancer and registered.
The most common cancer is non-melanoma skin cancer and its incidence is higher than that of general population.
Conclusion:
The study identify patient groups and cancer types, aids in surveillance programs, and provides information on warning transplant candidates about the possibility of cancer.
Level of evidence: Level II
Drawback of using registry data:
Data quality is variable and there is lack of follow-up.
I like your analysis of level of evidence of this study.
What are strengths of this study?
1. Please summarize this article
Introduction:
Increased risk of developing de novo cancer is an established complication of organ transplantation and the associated immunosuppression.
This is the first reported national study of de novo malignancy in British solid organ transplant recipients that makes comparisons with incidence rates in the general population and compares these incidences following the transplantation of different organs.
Materials and Methods:
Data on transplant recipients in the UK Transplant Registry, held by NHS Blood and Transplant, has been linked to information on cancer registrations following solid organ transplantation recorded by the eight cancer registries in England and the separate registries for Wales and Scotland.
Results:
Of the 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5% a lung (or heart/lung).
The median follow up period for this cohort of patients was 16 years (interquartile range: 8–26 years).
A total of 5706 patients (15%) developed a cancer in this period. In 3276 patients, the first cancer registered following transplantation was a NMSC, and of these 426 were subsequently registered as having developed a different de novo cancer.
Lymphoma rates are similar, except that non-Hodgkin’s lymphoma has a greater incidence in cardiothoracic.
The incidence of oral cancer in liver recipients is also high.
Following kidney transplantation, Standardized Incidence Ratios increases for some cancers (NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, esophagus and stomach) and decreases for others (Kaposi sarcoma, leukemia).
The SIRs for liver and ovarian cancer increase in the years immediately following transplantation and then decline, while the SIRs for breast, pancreas and uterine cancer remain constant.
Factors affecting time to cancer diagnosis:
Male.
Age.
Primary disease affected the risk of skin cancer in liver transplant.
Discussion:
recipients of a heart, kidney or liver, is over twice that of the general population and over three times higher in recipients of lung or combined heart and lung transplants .NMSC is the most common malignancy.
Study shows a very high incidence of post transplant lymphoma and Kaposi’s sarcoma.
E other cancer whose incidence is clearly increasing in renal transplant recipients over the study period is renal cell carcinoma.
Limitation of the study:
The registries do not distinguish between cancers arising in the native kidneys or in the transplant, and it is possible that the increase in incidence also reflects the aging donor population who may have an unrecognized renal cancer.
A weakness of the study is the lack of complete data on immunosuppression.
It is likely that the cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
2. What is the level of evidence provided by this article?
Level of evidence 11.
1. What are the drawbacks when we use the registry data?
Additional work for data collection
– Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders
– Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission.
– Target population depends on external validity (participating healthcare special disciplines)
– Non-homogeneous definition and scope of international registry items
– Complex data privacy issues
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomization
That is a superb analysis.
Ajay
Please summarise this article:
Introduction:
The recipients of solid organ transplantation are at increased risk of de novo malignancies, that is proposed to be due to immunosuppressive medications.
This mandates patients counseling and establishment of a screening and surveillance in the post-operative period.
This retrospective cohort study conducted in Britain comparing the incidence of different types of cancer in the post-transplantation recipients to general population incidence of cancer, in comparable base line characteristics – age, sex, gender, …etc.
Methods:
Retrospective cohort of 37617 transplant patients having NHS number from first 1January; 1980 to 31December; 2007, of them 25104 received kidney and kidney pancreas transplant, 18% received liver transplant, 10% heart transplant, and 5% received lung/heart lung transplant.
Exclusion crtiteria:
– Pancreas alone transplantation.
– Prevalent cancers at the time of transplantation.
– Cancers within a month post transplantation(except 620 patients diagnosed with PTLD).
– Multi-organ transplant recipients.
Results:
– NMSC is the commonest to occur after kidney transplant with 14 times more than the matched general UK population.
– The incidence of other malignancies were 2 times higher the general population, in all different organ transplants, quit higher in lung heart transplant patients.
– Lower incidence of malignancies noticed in liver transplant recipients, may be due to no induction therapy by the UK protocol, and lower immunosuppressive dosage used.
– PTLD incidence was higher in the first year after transplantation, non Hudgkin’s lymphoma more in cardiothoracic transplants.
– The incidence of cancers other than NMSC and PTLD in recipients aged > 50 is not much greater than that of the general population.
– Younger the age at transplant and males are more at risk of having cancer, BMI and whether or not the patient was on dialysis does not increase the risk of cancer.
– Breast, uterine, overian, prostate, pancreas cancers, and leukemias occurs in organ recipient at the same incidence with the general population.
Limitations:
– Lack of data on immunosuppression.
– Heart transplant patients received ATG induction therapy, and higher CNI levels needed, while liver recipients received lower immunosuppression.
– Underestimation of cancer incidence, as only the first cancer reported.
Conclusion:
– The study identify patient groups and cancer types, helps in surveillance program, and providing data on counselling pretransplant patients on the risk of malignancy.
– All transplant patients should be screened regularly for NMSC, oral and anal cancers, combined with lifestyle changes prevents sun exposure.
– Early detection of cancer in such patients does not translate to superior cure.
What is the level of evidence provided by this article?
Level of evidence II – retrospective cohort has been exposed to a risk /outcome.
What are the drawbacks when we use the registry data?
– Insufficient data form the medical charts, and data description.
– Absence of monitoring data, eg; different treatment protocols in different centers.
– Lack of comparable control group.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone.
That is a superb analysis.
Ajay
1. Please summarize this article
Introduction:
De-novo cancer in solid-organ-transplant recipients has a double 10-year incidence compared to the general population.
Aim of the study:
1-To assess the incidence of de-novo cancer in solid organ transplant recipients compared to general population.
2-To compare the incidence of de-novo cancers among different organs transplantation.
Study Design and methods:
This is a retrospective cohort study for all solid organ transplant recipients in England, Wales and Scotland between 01/01/1980 and 31/12/2007.
Data were collected from NHSBT from 8 cancer registries in England and registries in Wales and Scotland.
SIRs (standardized Incidence Ratios matched for age, gender and time period) were used to compare de-novo malignancy in Tx recipients with general population.
Inclusion:
1-Recipients of first kidney, liver, pancreas, heart or lung transplant.
2-Recipients who had an NHS number.
3-Known age and gender at time of transplantation.
Study Population: Total number of cohort 37617 recipients.
67% kidney Tx recipients. 18% liver Tx recipients. 10% a heart and 5%a lung (or heart/lung)
Exclusion:
Recipients with cancer diagnosed within first month’s post Tx. 33 pancreas alone Tx, and 177 multi-organ Tx recipients.
Follow up: from date of first transplant to the earliest of the date of first reported de-novo cancer or date of death within the study period. Median follow up was 16 years.
Results:
1-De-novo cancer in solid-organ-transplant recipients has a double 10-year incidence compared to the general population.
2-NMSC is 13 times higher incidence in Tx recipients.
3-The de-novo cancer SIR in lung transplant recipients is 3.6 as in general population.
4-Low incidence of cancer in liver Tx recipients is attributed to lack of induction IS and low doses of maintenance IS.
5-The incidence of PTLD is higher in the UK compared to Canada, Australia and Sweden.
6-Solid organ transplantation doesn’t increase the risk of breast or cervical cancer.
Study Weakness:
1-Absent data about IS protocols.
2-Underestimation of cancer incidence because it collected data about first de-novo cancer, so second cancer will not be recorded.
Recommendations:
Pre-transplant counselling.
Regular screening for NMSC, lip, and anal cancer.
Regular pelvic-abdominal USS for renal TX recipients to rule out cancer in native or Tx kidneys.
Regular USS liver to rule out HCC development.
2. What is the level of evidence provided by this article?
Level II, retrospective cohort study.
3. What are the drawbacks when we use the registry data?
1-Absent proper control group
2-Data collected from different registries and centers.
3-Selection Bias because of different assessment, non-random sampling and treatment criteria especially using the international classification of diseases over the duration of the study depending on the decade of ICD and data collected.
4-Lack of complete data especially that related to immunosuppression protocols and life style.
5-Heterogenous data description.
6-Subclinical cases may not be registered.
7-Data monitoring and validation are questionable and variable.
8-Follow up data is lost and outcomes are missed leading to underestimation of the incidence.
9-Complex statistical data to reduce errors.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone.
That is a superb analysis.
Ajay
Summary of article
An established complication of organ transplant and the associated immunosuppression is malignancy and its incidence is increasing. The largest standardize ration is very high for the cancer of lip, skin and PTLD, and anal but the incidence of type of cancer are different according to organ transplant
National registry data have been reported that recipient of kidney transplant from different country including Canada,swedon,japan,finland,Australia and the USA. Also from others studies data from large multicentre registries.
Cohart study consist of all patient transplanted in England, Wale and Scotland who received their first organ transplant including kidney, liver, heart, and lung from 1980 to 2007
WHO ICD-1 code was arranged for any new malignancy on the basis of available histology.
RESULT
Recipient characteristic in th e study from 37617 transplanted patients 67% were kidney 18% liver 10% heart and 5% lung were transplanted. Median follow up was 16 years.
15% patients develop cancer in this time period.
In 3276 patients they got cancer first time and registered.
From cancer the most common cancer is nonmelonoma skin cancer and its incidence is higher than general population.
The incidence of oral cancer is higher in liver transplant patients.
To conclude this in general the incidence if cancer in patient who received heart, kidney and liver is double than the general population and triple in lung and combined heart-lung transplanted patients.
Nonmelonoma cancer is most common in kidney and cardiothoracic transplant patients which id three time higher than liver transplant patients.
The incidence of NMSC is underestimated because of early diagnosis issue the lesion may be ablated and treated without histology.
Primary sclerosing cholagitis require liver transplant but the but its association with colitis that may leads to colon cancer and rectum.
Next cancer that have high incidence in kidney is renal cell carcinoma but it’s unclear.
The registries don’t distinguish between cancer arising from native kidney or transplanted kidney but possible cause is aging donor population may have underlying some renal cancer before transplantation and they may manifest later on.
Incidence of cancer in transplanted patients are might be because of they are immune compromised as they are very prone to develop viral infection rather they are on immunosuppressive medicine
This study has level 2
Drawback of registry data is;
1. Registry data can be used for different purpose. Using an available data for additional purposes, one needs to be sure that all the important information required to address a specific research question was collected in a manner that is sufficient to answer the question.
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone.
That is a good summary and an interesting analysis. Please type headings and sub-headings in bold or in underline.
Ajay
Comparison of the Incidence of Malignancy
in Recipients of Different Types of Organ:
A UK Registry Audit
====================================================================
Please summarise this article
Introduction
Aim
Methods
=================================================================
Result
============================================================
Research’s weakness:
====================================================================
What is the level of evidence provided by this article?
The level evidence is 3
===================================================================
What are the drawbacks when we use the registry data?
Registration data defect:
What is the level of evidence provided by this article?
The level evidence is 2
Why do you think that this article provides level 2 evidence? I am neither agreeing nor disagreeing for the sake of not biasing anyone.
thanks you alot Prof.Sharma
retrospective cohort studies or untreated control groups
Summary Of This Article
Introduction:
The Incidence Of Malignancy Is Increased After Solid Organ Transplantation. So, It Is Important To Identify The Risk Factors & Type Of Malignancy For Patient Education, Counseling And Screening.
The Aim Of The Study
To Study The Incidence Of Denovo Cancers In The Post-transplant Patient Recipient & Compare These Incidences Following The Transplantation Of Different Organs.
THE STUDY DESIGN
Retrospective Cohort Study Of 37617 Transplanted Patients
INCLUSION CRITERIA
All transplanted patients in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
EXCLUSION CRITERIA
Patients With Cancer Diagnosis Within One Month Of Transplant Were Excluded.
The Study METHOD
RESULT
Recipients Is Twice That Of The General Population, With The
Incidence Of Non-Melanoma Skin Cancer Being 13 Times Greater.
Lymphoproliferative Disease And Anal Cancer Have The Largest
Standardized Incidence Ratios, But The Incidence Of Different Types Of
Malignancy Differs According To The Organ Transplanted.
Are Different For Different Types Of Transplant Recipient, As Well As For Different Malignancies.
WEAKNESS OF THE STUDY
-The lack of complete data on immunosuppression.
-The cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
CONCLUSION
-The study suggest that all transplant recipients should be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure following transplantation
-Regular ultrasound scans for kidney transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is also indicated.
-The national cancer screening program may be affected by the results of this study
What is the level of evidence provided by this article?
-This was Retrospective cohort level II, comparing incidence rates of cancer in general population versus solid organ transplant recipients.
What are the drawbacks when we use the registry data?
when we use the registry data we should considered;
– Absence of an appropriate comparison group, Non random sampling
– The validity and generalizability of the registry
– Immunosuppression protocols were different in this period
– Identification is by the International Classification of Diseases (8, 9, or 10 depending on the decade of the study
– Underreporting from lack follow up may occur => which may underestimate rates of adverse events, Measurement error, Missing data and Missing outcomes
– Unregistered associated diseases;
– Lifestyle with incomplete data (body mass index, medications in use, smoking history);
– Patients seen in diverse centers /countries
– Laboratory targets that they modified (fasting blood glucose, for example);
– Heterogenicity in data description;
– Complex statistical data in an attempt to minimize errors
Dear colleagues,
Please go through this reference to decide the level of evidence:
https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009
Comparison of the Incidence of Malignancy in Recipients of Different Types of Organ: A UK Registry Audit.
Introduction:
Malignancy post organ transplant is one of the most common long term complications which is mainly multifactorial, here is UK transplant registry on cancer following solid organ transplantation.
Methods and Statistical methods.
NHS Blood and Transplant (NHSBT) collect data on transplant recipients (between 1 January 1980 and 31 December 2007 )in the UK Transplant Registry which was recorded by the eight cancer registries in England and the separate registries for Wales and Scotland and the cohort consists of 37 617 transplanted patients.
Standardized incidence ratios calculated by comparing the incidence rates in the transplanted population with the general population, using matched for age, gender and time period and calculated the cumulative incidence of different cancers.
Results.
1-The 37 617 transplanted patients, 25 104 (67%) received a kidney (or simultaneous kidney and pancreas), 18% a liver, 10% a heart and 5%a lung (or heart/lung) with median follow up period for this cohort of patients was 16 years and (15%) developed a cancer in this period mainly a NMSC and others registered as de novo cancer .
2- The overall incidence rate of cancer in the transplanted population is just over twice that of the general population
3- 10- years after transplantation, recipients have an overall incidence rate of 90 per thousand patients, which is more than double the 10-year incidence rate for the population of England which was 36 in the same period and standardized incidence was 14.4 which means that a transplant recipient is over 14 times that of the general population.
4- The standardized incidence ratios are particularly high for non-melanoma skin cancer, cancer of the lip and Kaposi sarcoma.
5- NMSC is the most common malignancy, with an SIR of over 16 for kidney and cardiothoracic transplant recipients.
Weakness points:
1-The lack of complete data on immunosuppression.
2-Change of immunosuppression protocol between organs( some received monotherapy and others received ATG with CNI based triple therapy).
What is the level of evidence provided by this article?
Level of evidence III (retrospective study).
What are the drawbacks when we use the registry data?
1-Variable quality of the collected data.
2-Lack of active follow-up (which may underestimate rates of adverse events).
Why do you think that this article provides level 3 evidence?
Ajay
Introduction:
Post transplant denote malignancies is a well known complication of transplantation ( due to high doses of immunosuppression). Pre-transplant patient counciling about risk of malignancy development and need for post transplant screening and surveillance are crucial.
Aim of the study:
Compare between de novo cancer incidence and incidence in general population, and compare incidence of de novo cancer after transplant of different organs.
Method:
Result & discussion:
level of evidence is 2
Drawback of registry data:
That is an excellent summary and very well structured reply, dear Dr Ban
Please summarise this article
The results
Conclusion
What is the level of evidence provided by this article?
What are the drawbacks when we use the registry data?
Why do you think that this article provides level 3 evidence?
Ajay
Please summarise this article
Malignancy occur in a higher frequency in transplant recipients when compared to general population
This is mainly because of the immunosuppression, other important factor includes associated premalignant conditions that predispose to organ failure such as smoking as a cause of lung failure may cause other types of cancers, PSC as a cause of liver failure (which may be associated with colon cancer)
The current study is addressing the incidence of denovo solid organ malignancy in different organ transplantation using data registry from Britain including 37 617 transplanted patients in comparison to general population matched in age and sex
The results
The incidence of denovo cancer in renal, heart and liver transplant recipients is 2 times higher than general population while it is 3 times higher in recipients of lung or combined heart and lung transplants
The incidence of NMSC is 13 times that of general population
The incidence of lip and anal cancer is lower in liver transplantation, which may be due to lack of biological induction and avoidance of azathioprine in maintenance immunosuppression
The most common malignancies occurring in renal transplant recipients in the current study are NMSC, PTLD, lip and anal cancer and RCC, on the other hand the incidence of breast cancer is not increased due to unclear reason and the incidence of cervical cancer also is not higher which may be explained by active surveillance programs.
Conclusion
Malignancy occurring more frequently in organ transplantation, the frequency differ according to the type of transplant and site of cancer.
What is the level of evidence provided by this article?
This is a retrospective cohort level of evidence II
What are the drawbacks when we use the registry data?
It depends on voluntary reporting so may underestimate the incidence rate
It may be collected from several countries which may be associated with bias due to loss of reference population
Sorry … level of evidence III
Why do you think that this article provides level 3 evidence?
Ajay
THE AIM OF THE STUDY:
—————————————————————
Is to study the incidence of denovo cancers in the allograft recipient, and compare these incidences following the transplantation of different organs.
THE STUDY DESIGN :
——————————————————-
Retrospective cohort study .
THE POPULATION;
——————————————————–
The cohort consists of 37617 transplanted patients.
THE INCLUSION CRITERIA :
————————————————————-
All transplanted patients in England, Wales and Scotland, who received a first kidney, liver, heart or lung transplant between 1 January 1980 and 31 December 2007, and who had an NHS number.
THE EXCLUSION CRITERIA;
———————————————————
1- Patients with cancer diagnosis within one month of transplant were excluded.
THE METHOD;
————————————————————
Data in the UK Transplant Registry held by NHS Blood and Transplant (NHSBT) were linked with data made available by the cancer registries in England, Scotland
and Wales. Incidence rates in the transplanted population were then compared with the general population, using standardized incidence ratios matched for age, gender and time period.
THE RESULT ;
————————————————————————-
1-The 10-year incidence of de novo cancer in transplant recipients is twice that of the general population, with the incidence of non melanoma skin cancer being 13 times greater.
2-Non melanoma skin cancer, cancer of the lip, post-transplant lymphoproliferative disease and anal cancer have the largest standardized incidence ratios, but the incidence of different types of malignancy differs according to the organ transplanted.
3-Patterns in standardized incidence ratios over time since transplantation are different for different types of transplant recipient, as well as for different malignancies.
THE WEAKNESS OF THE STUDY;
——————————————————–
1-The lack of complete data on immunosuppression.
2-The cancer incidence rates in this study are underestimates, since the study has censored a recipient at the first occurrence of any cancer (except NMSC), so if a recipient developed a second cancer this would not be recorded.
CONCLUSION;
—————————————————————–
1-The study identify patient groups and cancer types, which should form part of a cancer surveillance program, and provide data for counselling pre transplant patients on the risk of malignancy.
2-following transplantation ,the study suggest that all transplant recipients should
be screened regularly for NMSC, including lip and anal cancer, and that this should be combined with lifestyle changes to reduce sun exposure .
3- Patients undergoing liver transplant for alcohol should have regular surveillance of the aero digestive tract, and those with a diagnosis of primary sclerosing cholangitis who have their colon and rectum in situ should undergo regular colonoscopy.
4-The presence of recurrent graft cirrhosis should also be a cue to regular ultrasound surveillance for hepatocellular carcinoma.
5-Similarly a case can be made for subjecting renal transplant recipients to regular
ultrasound scans of their transplant and native kidneys for evidence of tumor, particular those transplanted for analgesic nephropathy or aristolochia-related interstitial nephritis in whom a cystoscopic examination of the urothelium is also indicated.
What is the level of evidence provided by this article?
——————————————————————————
LEVEL III
What are the drawbacks when we use the registry data?
—————————————————————————————
1-Variable quality of the collected data.
2-Lack of active follow-up (which may underestimate rates of adverse events).
3-NO specific tool exists for assessing the quality of a registry-based study.
4- Absence of an appropriate comparison group.
5- The validity and generalizability of the registry .
REFERENCE:
1- Injury Available online 11 December 2021 In Press, Corrected Proof What are Corrected Proof articles?Registries: Big data, bigger problems?
Why do you think that this article provides level 3 evidence?
However, that is an excellent summary and very well structured reply, dear Dr Abdelrehman.
Ajay
This study is a historical cohort (level 2 of evidence) with patients who received their first organ donated between January 1980 and December 2007, crossing information from the British Transplant Registry with oncological records using the international code of diseases in England, Scotland, and Wales. The control group was selected from the general population with similar characteristics. Pancreas and multivisceral transplants were excluded. Patients diagnosed with cancer within the first thirty days after transplantation were also excluded, except for 620 patients who developed PTLD. The total number of patients included in the study was 37,617.
The analysis spanned 15 years after transplantation and was separated by type of transplant and cancer involved. Transplanted organ, age, sex, primary disease, smoking history, obesity (BMI greater than 30), dialysis at the time of transplantation, and the year in which it was performed was considered. Some data limitations such as BMI, immunosuppressant dose, and smoking history limited the statistical index.
Of these transplants, 25,104 (67%) were kidney, 18% liver, 10% heart, and 5% lung. A total of 5,706 patients (15%) developed cancer during this period. Ten years after transplantation, the risk of developing cancer is twice that of the general population, but specific cancers were more frequent. Non-melanoma skin cancers are more common with a 14.4% higher risk; in non-melanoma skin kidney transplantation it was 16.6; lips 65.6; Hodgkin’s Lymphoma 7.4; Non-Hodgkin lymphoma 12.5; breast 1.0; oral cavity 4.2; colorectal 1.8; anus 10; liver 2.4; lung 1.4; Kaposi’s sarcoma 17.1; kidney 7.9 and multiple myeloma 3.3.
Male sex and advanced age are risk factors. The type of transplant as well as the type of cancer are variable and present different data. Non-melanoma skin cancer is three times more frequent in kidney, heart, and lung transplantation when compared to liver transplantation. Some environmental situations (smoking load and exposure to oncogenic viruses) increase the risk for specific neoplasms.
Breast and prostate cancer do not seem to be related to an increase in frequency in transplant patients. A weakness of the study is the lack of data on immunosuppression and objective lifestyle data.
This study suggests an active and passive search for the investigation of non-melanoma skin cancer, without the need for additional investigation for breast and prostate cancer. The need for screening to investigate neoplasia due to potential oncogenic viruses is debatable and should be individualized and discussed with the patient by a multidisciplinary team.
Drawbacks
Some facts should be considered in registry studies:
1. Immunosuppression protocols were different in this period;
2. Identification is by the International Classification of Diseases (8, 9, or 10 depending on the decade of the study);
3. Underreporting may occur;
4. Unregistered associated diseases;
5. Lifestyle with incomplete data (body mass index, medications in use, smoking history);
6. Laboratory targets that they modified (fasting blood glucose, for example);
7. Heterogenicity in data description;
8. Complex statistical data in an attempt to minimize errors
Hi dr Batista,
I like your description of inherent drawbacks of this study.
Ajay
Thank you, Professor
-Immunosuppression and organ transplantation raise cancer risks.
-In this British study on cancer incidence in solid organ transplant recipients, we assess the incidence of de novo malignancies in allograft recipients after organ transplantation. The UK Transplant Registry has data from cancer registries in England, Scotland, and Wales. This data came from NHSBT.
To compare transplanted and general population incidence rates, age, gender, and time were used to find standardized incidence ratios that were the same for both groups.
Transplant recipients had a 10-year risk of de novo cancer that was doubled, and nonmelanoma skin cancer was 13 times higher.
The highest standardized incidence ratios are for non-melanoma skin cancer, lip cancer, post-transplant lymphoproliferative illness, and anal cancer. Malignancies vary with organ transplants. Standardized incidence ratios vary by transplant recipient type and malignancy. These findings affect nationwide screening programs.
-Cancer incidence is about twice as high in transplanted people.
-Nonmelanoma skin cancer, lip cancer, and Kaposi sarcoma have high SIRs.
-Lung transplants had the highest SIR.
-Liver transplant recipients had lower rates of nonmelanoma skin cancer and lip cancer.
-Non-lymphoma Hodgkin’s is more common among cardiothoracic transplant patients. —Oral cancer is common among liver recipients, although 15 of 18 cases were in patients with alcoholic liver disease.
-As predicted, posttransplant lymphoma and Kaposi’s sarcoma had the highest incidence of all malignancies except NMSC.
-This research censored recipients at the first occurrence of any cancer (excluding NMSC), thus if they acquired a second cancer, it would not be reported. This may have underestimated cancer incidence rates.
-Breast cancer is one kind of cancer whose prevalence was not raised in our research and may perhaps be decreasing.
-Some transplanted illnesses are linked to other cancers or toxic exposure. Smoking may cause lung and heart transplants (emphysema and ischemic cardiomyopathy), as well as various cancers.
-NMSC incidence in kidney transplant patients was unchanged by three-month azathioprine, MMF, tacrolimus, or ciclosporin treatment. Other cancers have inadequate data for estimations.
Limitation:
A weakness of the study is the lack of complete data on immunosuppression.
Retrospective cohort study, level of evidence 3
-Additional work for data collection
– Possible changes in the long term (accounting system, classifications)
– Possible influence of confounders – Need for external and internal validation of collected data
– Often no data monitoring/validation; different local conditions in data collection and submission
– Target population depends on external validity (participating healthcare special disciplines)
– Non-homogeneous definition and scope of international registry items
– Complete and long-term follow-up remains challenging
– Need for sophisticated statistical analyses to compensate for the impact of non-randomisation.
Hi Dr Nazer,
Why do you think that this article provides level 3 evidence?
This study would have inherent limitations as for any secondary data. I like your list of limitations of this study.
Ajay
Please summarise this article
This is the first study to calculate standardized incidence ratios (SIRs) of de novo cancers in solid organ transplant recipients from 1980 to 2007 UK national registry data.
Results:
1.Overall cancers in solid organ transplant patients:
2.Cancers in relation to kidney transplant recipients:
3.Cancers in relation to liver transplant recipients:
4.Cancers in relation to lung or combined lung and heart transplantation:
5.Cancers in relation to heart transplant recipients :Overall SIR:2.5
What is the level of evidence provided by this article?
Level 3 (Retrospective, case-control, non-experimental observational study comparing incidence rates of cancer in general population versus solid organ transplant recipients)
What are the drawbacks when we use the registry data?
The following are some disadvantages or biases associated with registry data (1, 2, 3).
A. Selection Bias
B. Information bias:
C. Confounding bias, occurs either by group or indication:when measured or unmeasured factors that affect the outcome of interest are unevenly distributed among study arms.
D. Other bias:
References:
That is an excellent summary and very well structured reply, dear Dr Yadav.
Is it really a case-control study?
This study analyzed the transplant cohort and the standardized incidence ratio calculated from the registry data shows that the transplant cohort had more cancers compared to the general population. The general population used for the calculation/inference can be viewed as a “quasi-control group”
1- Summary
Introduction
Denovo cancer risk is high in organ transplant recipients and as immunosuppression complication.
Shedding light on the importance of explaining the risk to patients pretransplant and screening posttransplant.
This is the first British study on de novo malignancy comparing it’s incidence in organ transplant recipients versus in the general population .
Methods
This cohort study included all kidney ,liver,lung and heart transplant recipients with NHS number in England ,Wales and Scotland within 27 years.
The study included 37 617 transplanted patients followed from the first
transplant time till the first reported de novo malignancy or death within the study period.
Standardised incidence ratio was used to assess cancer incidence
Results
67% of the cases received a kidney transplant ,18% liver, 10% heart and 5% lung transplants within median follow up period of 16 years.
2856 patients were registered with a de novo cancer excluding nonmelanoma skin cancer.
The incidence rate of cancer for transplant recipients in 10 years after transplantation is more than double the incidence rate in the general population. The risk of NMSC occurrence is 14 times more in transplant recipients than in general population.
The overall incidence rate of cancer in the transplant recipients is more than twice that of the general population specially for NMSC, cancer of the lip and Kaposi sarcoma.
Lung transplant recipients had highest SIR.
Liver recipients had lowest incidence of NMSC and lowest SIR for lip cancer, and high incidence of oral cancers particularly with alcoholic liver disease.
Non Hodgkin lymphoma was highly associated with cardiothoracic transplant recipients .
SIR is high at the beginning of transplantation period and decreases with time but malignancy pattern varies between organs .
For kidney transplantation, SIR increases for NMSC, anus, cervix, Hodgkin’s lymphoma, kidney, oesophagus and stomach cancer and decreases for Kaposi sarcoma, leukaemia. SIRs for liver and ovarian cancer is high and decreases with time and that for breast, pancreas and uterine cancer is stationary.
SIRs for each cancer is inversely proportion to age .
Factors affecting time to cancer diagnosis showed high risk in male and increased with age .
The age and primary disease affected the risk of skin and colon cancer development in liver recipients .
PTLD risk is affected by gender and lung cancer risk depended on age group.
NMSC risk in kidney transplant recipients was unaffected by azathioprine , MMF ,tacrolimus or ciclosporin use.
Discussion
Cancer incidence in heart ,kidney and liver is more than double the incidence in general population and more than 3 times that of lung transplantation or combined cardiothoracic transplantation.
The most common malignancy is NSMC meanwhile their incidence could be underestimated due to lack of data .
Lip and anal canal cancers had low incidence in liver recipients.
NMSC is associated with viral infection and lower association with use of lower immunosuppressive doses.
The incidence rate of cancers in UK was similar to Australia , Canada and Sweden but there were some variations as UK had higher incidence of non Hodgkin lymphoma while Canada and Australia showed higher kidney cancer incidence.
Some diseases necessitating transplantation can be an indicator of exposure to a specific carcinogen .
Posttransplant lymphoma incidence in kidney recipients increased nearly 9 times within 4 years period due to the advances in immunosuppressives and antimicrobials.
Renal cell carcinoma incidence is increased in renal transplant recipients due to older recipients’ age and it’s association with acquired cystic kidney disease.
Data did not clarify if cancer originated from native or transplanted kidneys .
Breast cancer had low incidence in this study.
Cervical cancer screening programme with early detection and treatment in UK justify the low incidence of cancer cervix.
Limitations of this study include absence of data on immunosuppressives used, underestimating cancer risk.
This study advices for regular screening for NMSC along with lifestyle changing and lower sun exposure, primary sclerosing cholangitis cases need to undergo regular colonoscopy,liver cirrhosis cases need regular screening for HCC also renal transplant recipients require regular US screening for cancer of graft or native kidney.
Early identification of cancer in immunosuppressed cases does not guarantee high cur rate .
2- Level of evidence is 3
3- Drawbacks of using registry data include possible changes in the long term ,cofounders possible influence, validation of collected data is needed ,different local conditions in data collection and submission, Non homogeneity ,data privacy issues , long-term follow-up is difficult.
Hi Dr Doaa,
Why do you think that this article provides level 3 evidence?
Ajay
Because it was retrospective study obtained from registered data ,meanwhile it is a cohort study so can be level II
1.Patients seen in diverse centers/countries
2.Assessment or treatment criteria may not be uniform i.e potential for selection bias
3.Incomplete data registration (weakness of the above study)
4.Loss of follow up data
5.Missing outcomes
Yes, Dr Ben.
This study would have inherent limitations as for any secondary data.
Ajay
Yes,agree with you prof
The incidence of de novo malignancy post-transplant is higher than general population because of immunosuppression medications , and the incidence of specific malignancy differ from solid organ to another as documented by British registry in Britain.
In heart, liver and kidney post-transplant, the incidence of overall malignancy with the exclusion of non-melanoma skin cancer NMSC is 2- fold increase than general population (SIR 2.5, 2.2, 2.4) and more than 3-fold increase in lung and combined heart and lung transplant recipient (SIR 3.6).
SIR is standardized incidence ratio, which is the relation between number of observed cases and number of expected cases.
SIR of NMSC post kidney and cardiothoracic transplant is 16, this is 3 fold increase than post liver transplant.
The incidence of cancer may be under-estimated because of removal or ablation of the skin lesions without biopsy and histological examination.
Also the incidence depends on registration which differs from country to country and it is affected by many factors.
level of evidence 3
Hi Dr Riham,
Why do you think that this article provides level 3 evidence?
Ajay
it is retrospective cohort