1. Liver Transplantation and Subsequent Risk of Cancer: Findings from a Canadian Cohort Study By Scott, Berkeley and Rob Music by Black Sabbath

2. Liver Transplantation and Subsequent Risk of Cancer: Findings from a Canadian Cohort Study Case 2 Journal Club By: Berkeley, Rob and Scott Cohort Study

3. Study Outline Objective: Characterizing patterns of cancer incidence among liver transplant recipients with respect to rates experienced by the general Canadian population. Study Design: Retrospective Cohort Setting: Canada Participants: Canadians having undergone liver transplant betwixt the years of 1983 and 1998. Data Collection: Personal information from the CORR (Canadian Organ Replacement Registry) cross referenced with the CMDB (Canadian Mortality Database) and the CCR (Canadian Cancer Registry). Passive Surveillance. Main Outcome: Incidence of cancer Analytic Method: Calculation of Standardized Incident Ratios (SIR)

4. Analytic Methods! Part Deux Inclusion criteria: Canadian liver transplant recipients between June 1983 and October 1998 (# 2545) Exclusion criteria: Pre-existing cancer excluding non-melanoma skin cancer (# 212) Cancers occuring within the first 30 days after transplant (#278) Liver cancer cases (#21) Patients included: # 2034 CORR database linked with CMDB database to ascertain cause of death among the cohort utilizing the generalized record linkage system (98-100% chance of correctly identifying patients) CORR database linked with CCR database to ascertain cancer incidence among the cohort (CCR captures 95% of incident cancers in Canada) Patterns of cancer incidence among the liver transplant cohort and the general Canadian population were compared using the standardized incidence ratio (SIR) = ratio of observed incident cancers to the expected number. Stratified analysis done to examine risk secondary to age at transplant, sex, time since transplantation and year of transplantation Internal cohort analysis using Cox proportional hazards regression model to evaluate effects of age, sex & transplant year

8. Results V

14. Conclusions/Implications Cancers are more common in the post-liver transplant population NHL (likely PTLD) is the most common type found Cancer risk highest in first year post transplant Cancer risk highest in those who get a transplant at a younger age. Cancer screening for some cancers (i.e. colorectal) may need to be re-visited. Prospective studies looking at specific drugs ( i.e. mTOR vs CI) with regards to cancer risk may be in order.

15. Strengths Large population size Nationwide sampling Multivariate analysis Comparison of groups within the same timeline

16. Weaknesses Unclear primary diagnosis 30 day post transplant cutoff for exclusion All patients are Canadian thus inherently weak Elderly men with unexplained cancer rate increase Breast cancer findings insufficiently powered Colon cancer rates could be artificially inflated by co- morbidities (i.e. IBD) SIR calculations in young patients inflated by low expected incidence. Heterogeneity pre and post transplant Shifting demographics in tables

17. Discussion Points Why do I care? We will all take care of post-transplant patients during our career. Studies such as this show that this patient population is at an increased risk of cancer and that we should make sure they are appropriately screened for cancer.

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