The 28‐year incidence of de novo malignancies after liver transplantation: A single‐center analysis of risk factors and mortality in 1616 patients

Abstract

De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow-up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3-81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio [HR], 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A-treated compared with tacrolimus-treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow-up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404-1414 2017 AASLD.

Active Smoking Before Liver Transplantation in Patients with Alcohol Use Disorder: Risk Factors and Outcomes

“…The current study emphasizes that smoking is related to worse LT outcomes. Similar to our findings, there is evidence that smoking history correlates with development of cancer after LT [ 8 , 9 , 20 , 21 , 22 ], especially among ALD patients, with the joint use of alcohol and tobacco having higher carcinogenic effects [ 23 , 24 ].…”

De novo malignancies after liver transplantation: The effect of immunosuppressionn-personal data and review of literature

“…The vast majority of non-melanoma skin cancer is represented by squamous cell carcinomas and basal cell carcinomas[18,35]. However, a recent report from Rademacher et al[37] described an inverted trend with a decline in the incidence of skin cancer in the OLT population. This suggests that the characteristics of the analyzed cohort and a more deliberate use of sun blockers, avoidance of direct UV radiation and the type of IS adopted may play a role[38,39].…”

Keratinocyte Carcinomas: Current Concepts and Future Research Priorities

“…A specific azathioprine signature mutation has recently been identified in cSCC (47); procarcinogenic mechanisms for the calcineurin inhibitor, cyclosporine, include reduced UV DNA damage repair (48), reduced apoptotic response to UV (49), and ATF3 induction and suppression of p53-dependent senescence (48,50). In contrast, mTOR inhibitors are associated with reduced cSCC risk, possibly through both antiproliferative and antiangiogenic properties (34,(51)(52)(53) and the risk associated with newer immunosuppressive drugs, including tacrolimus and mycophenolate, may also be reduced, but supportive epidemiologic data are not yet established (54,55). Voriconazole, an antifungal agent commonly used in transplantation, has direct photocarcinogenic effects (56) and is associated with significantly increased risk of aggressive cSCC (57).…”