Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection

Abstract

The goal of this study was the characterization of long-term cancer risks after liver transplantation (LT) with implications for prevention and detection. Site-specific cancer incidence rates and characteristics were compared retrospectively for 2000 LT patients from a single institution (January 1, 1983 to December 31, 2010) and the general German population with standardized incidence ratios (SIRs); the total follow-up at December 31, 2011 was 14,490 person-years. The cancer incidence rates for the LT recipients were almost twice as high as those for the age- and sex-matched general population (SIR = 1.94, 95% CI = 1.63-2.31). Significantly increased SIRs were observed for vulvar carcinoma (SIR = 23.80), posttransplant lymphoproliferative disorder/non-Hodgkin lymphoma (SIR = 10.95), renal cell carcinoma (SIR = 2.65), lung cancer (SIR = 1.85), and colorectal cancer (SIR = 1.41). The mean time between transplantation and diagnosis was 6.8 years. The mean age at the time of diagnosis was significantly lower for the cohort versus the general population with similar malignancies [50 years (both sexes) versus 69 and 68 years (males and females), P ≤ 0.006]. Tumors were diagnosed at more advanced stages, and there was a trend of higher grading, which suggested more aggressive tumor growth. Tumor treatment was performed according to accepted guidelines. Surprisingly, 5-year survival was slightly better in the study cohort versus the general population for renal cell carcinoma, lung cancer, colorectal cancer, and thyroid cancer. Long-term immunosuppression with different protocols did not lead to significantly different SIRs, although patients treated with mycophenolate mofetil had the lowest SIR for de novo cancers (1.65, 95% CI = 1.2-2.4). Alcoholic liver disease (SIR = 2.30) and primary sclerosing cholangitis (SIR = 3.40) as indications for LT were associated with an increased risk of de novo malignancies. In conclusion, risk-adapted cancer surveillance is proposed. Tumor treatment performed according to accepted guidelines appears adequate. Mycophenolate may lead to lower long-term risks for de novo cancers.

Donor-Transmitted, Donor-Derived, and De Novo Cancer After Liver Transplant

“…14 A Europe-wide analysis undertaken by Eurotransplant concluded that the risk of de novo cancer for liver transplant recipients was very similar to the Australian data with an SIR of 1.94 (CI:1.53-2.44). 12 Lung cancer, colorectal cancer, lymphoma, renal cell carcinoma, thyroid cancer, and vulvar cancers were significantly increased in this cohort. In the United States, an analysis of 175 732 organ transplant recipients of which 37 888 received a liver allograft, were compared with the general US population using 14 US regional cancer registries.…”

“…Single-center cohort studies have also proved useful, but the number of life years of follow-up after transplant are usually insufficient for detailed analyses, though some specific inferences can be made. 11 Analyses of de novo cancer in liver transplant recipients have now followed the renal transplant methodologies, and there are publications from the European, 12 Australian, 13,14 and US registry experiences. 9 In their analysis of 1926 Australian Liver transplant recipients followed between 2.2 and 10 years after transplant (median, 6 y), Na and associates 13 compared a sex-and age-matched general Australian population and noted an increased Standardized Incidence Ratio (SIR) of 2.20 (confidence interval (CI) 1.87-2.57).…”

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“…10 Schrem and associates reported that cancer incidence rates for liver transplant recipients were almost twice as high as those for an age-matched and sex-matched general population. 11 In another study from the United States, the authors showed a statistically significant increased risk for oropharyngeal cancer when they looked at several cancer types and compared them with the general population. 9 Recent studies have shown that at all tumor groups, especially skin cancers and lymphomas have a 10-fold increased risk when compared with the agematched and sex-matched general population.…”

The Onset of de novo Hepatocellular Carcinoma after Liver Transplantation can be both of Donor and Recipient origin. A Case Report

“…Both microsatellite analysis and fluorescent in situ hybridization revealed the recipient origin of the tumor, potentially due to tissue chimerism. [4,5].…”