The Long‐Term Benefit of Liver Transplantation for Hepatic Metastases From Neuroendocrine Tumors

Selection criteria and benefit of liver transplantation for hepatic metastases from neuroendocrine tumors (NETs) remain uncertain. Eighty‐eight consecutive patients with metastatic NETs eligible for liver transplantation according to Milan‐NET criteria were offered transplant (n = 42) versus nontransplant options (n = 46) depending on list dynamics, patient disposition, and age. Tumor burden between groups did not differ. Transplant patients were younger (40.5 vs. 55.5 years; p < 0.001). Long‐term outcomes were compared after matching between groups made on multiple Cox models adjusted for propensity score built on logistic models. Survival benefit was the difference in mean survival between transplant versus nontransplant options. No patients were lost or died without recurrence. Median follow‐up was 122 months. The transplant group showed a significant advantage over nontransplant strategies at 5 and 10 years in survival (97.2% and 88.8% vs. 50.9% and 22.4%, respectively; p < 0.001) and time‐to‐progression (13.1% and 13.1% vs. 83.5% and 89%; p < 0.001). After adjustment for propensity score, survival advantage of the transplant group was significant (hazard ratio = 7.4; 95% confidence interval (CI): 2.4–23.0; p = 0.001). Adjusted transplant‐related survival benefit was 6.82 months (95% CI: 1.10–12.54; p = 0.019) and 38.43 months (95% CI: 21.41–55.45; p < 0.001) at 5 and 10 years, respectively. Liver transplantation for metastatic NETs under restrictive criteria provides excellent long‐term outcome. Transplant‐related survival benefit increases over time and maximizes after 10 years.     

Decreasing incidence of cancer after liver transplantation—A Nordic population‐based study over 3 decades

Cancer remains one of the most serious long‐term complications after liver transplantation (LT). Data for all adult LT patients between 1982 and 2013 were extracted from the Nordic Liver Transplant Registry. Through linkage with respective national cancer‐registry data, we calculated standardized incidence ratios (SIRs) based on country, sex, calendar time, and age‐specific incidence rates. Altogether 461 cancers were observed in 424 individuals of the 4246 LT patients during a mean 6.6‐year follow‐up. The overall SIR was 2.22 (95% confidence interval [CI], 2.02‐2.43). SIRs were especially increased for colorectal cancer in recipients with primary sclerosing cholangitis (4.04) and for lung cancer in recipients with alcoholic liver disease (4.96). A decrease in the SIR for cancers occurring within 10 years post‐LT was observed from the 1980s: 4.53 (95%CI, 2.47‐7.60), the 1990s: 3.17 (95%CI, 2.70‐3.71), to the 2000s: 1.76 (95%CI, 1.51‐2.05). This was observed across age‐ and indication‐groups. The sequential decrease for the SIR of non‐Hodgkin lymphoma was 25.0‐12.9‐7.53, and for nonmelanoma skin cancer 80.0‐29.7‐10.4. Cancer risk after LT was found to be decreasing over time, especially for those cancers that are strongly associated with immunosuppression. Whether immunosuppression minimization contributed to this decrease merits further study.     

Living donor liver transplantation for biliary atresia: An analysis of 2085 cases in the registry of the Japanese Liver Transplantation Society

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in pediatric population. This study analyzed the comprehensive factors that might influence the outcomes of patients with BA who undergo living donor LT by evaluating the largest cohort with the longest follow‐up in the world. Between November 1989 and December 2015, 2,085 BA patients underwent LDLT in Japan. There were 763 male and 1,322 female recipients with a mean age of 5.9 years and body weight of 18.6 kg. The 1‐, 5‐, 10‐, 15‐, and 20‐year graft survival rates for the BA patients undergoing LDLT were 90.5%, 90.4%, 84.6%, 82.0%, and 79.9%, respectively. The donor body mass index, ABO incompatibility, graft type, recipient age, center experience, and transplant era were found to be significant predictors of the overall graft survival. Adolescent age (12 to <18 years) was associated with a significantly worse long‐term graft survival rate than younger or older ages. We conclude that LDLT for BA is a safe and effective treatment modality that does not compromise living donors. The optimum timing for LT is crucial for a successful outcome, and early referral to transplantation center can improve the short‐term outcomes of LT for BA. Further investigation of the major cause of death in liver transplanted recipients with BA in the long‐term is essential, especially among adolescents     

More severe deficits in functional status associated with higher mortality among adults awaiting liver transplantation

The impact of functional status on liver transplant (LT) waitlist outcomes is not well studied. Early evidence suggests frailty portends increased mortality. We aim to evaluate the association of functional status with LT waitlist survival and the probability of receiving LT among adults with cirrhosis. Using 2005‐2016 United Network for Organ Sharing (UNOS) data, we retrospectively assessed the association of functional status, as determined by Karnofsky Performance Status Score (KPSS) with LT waitlist survival and the probability of receiving LT using Kaplan‐Meier and multivariate Cox proportional hazard models. Among 118 954 patients listed for LT, patients with worse Karnofsky scores, indicating poor functional status, were progressively more likely to receive liver transplantation compared to patients with better scores, with the most functionally disabled group having 68% higher probability of receiving LT (HR 1.68; 95% CI 1.61‐1.75, P < 0.001). Worse functional status was associated with increased waitlist mortality, with the most functionally disabled group 97% more likely to die on the waitlist (HR 1.97; 95% CI 1.81‐2.16, P < 0.001). In conclusion, among patients awaiting LT, worse functional status was associated with significantly higher waitlist mortality.     

Posttransplant lymphoproliferative disorder in pediatric patients: Survival rates according to primary sites of occurrence and a proposed clinical categorization

Posttransplant lymphoproliferative disorder (PTLD) is a devastating complication of organ transplant. In a hospital‐based registry, we identified biopsy‐proven cases of PTLD among children during a 15‐year period and reviewed trends in PTLD rates, the sites of involvement, and the associated survival rates. Cases that were included had at least 1 year of follow‐up after the diagnosis of PTLD. We studied 82 patients with first‐episode PTLD. Median age at diagnosis was 6.4 years (IQR 3.2‐12.3 years). The most frequent PTLD sites were tonsillar/adenoidal (T/A [34%]) and gastrointestinal (32%), followed by miscellaneous (defined as less common sites including central nervous system, kidney, lung, and soft tissue [12%]), lymph node (11%), and multisite (11%). Kaplan‐Meier survival curves showed that T/A PTLD was associated with decreased all‐cause mortality compared with PTLD at other sites (log‐rank 0.004), even after adjustment for histological subtype (P = .047). PTLD‐related mortality was also decreased among T/A PTLD (log‐rank 0.012) but showed a trend toward significance only after adjustment for histological subtype (P = .09). Among first episodes of PTLD, T/A PTLD was associated with a survival advantage compared with PTLD at other sites, even after adjustment for potential confounders. Based on our observations, we propose a clinical categorization of PTLD according to anatomical site of occurrence.     

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

Regorafenib is one option for second‐line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib‐tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second‐line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib‐treated LT patients (2015‐2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty‐eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1‐18.5) years; median time on sorafenib was 11.3 (0.7‐76.4) months and 14 (1‐591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty‐four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7‐19.1) and 38.4 months (95% CI, 18.5‐58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision‐making in sorafenib‐tolerant patients with HCC recurrence after LT.     

Risk Factors for De Novo Malignancy Following Lung Transplantation

Risk factors for non–skin cancer de novo malignancy (DNM) after lung transplantation have yet to be identified. We queried the United Network for Organ Sharing database for all adult lung transplant patients between 1989 and 2012. Standardized incidence ratios (SIRs) were computed by comparing the data to Surveillance, Epidemiology, and End Results Program data after excluding skin squamous/basal cell carcinomas. We identified 18 093 adult lung transplant patients; median follow‐up time was 1086 days (interquartile range 436–2070). DNMs occurred in 1306 patients, with incidences of 1.4%, 4.6%, and 7.9% at 1, 3, and 5 years, respectively. The overall cancer incidence was elevated compared with that of the general US population (SIR 3.26, 95% confidence interval [CI]: 2.95–3.60). The most common cancer types were lung cancer (26.2% of all malignancies, SIR 6.49, 95% CI: 5.04–8.45) and lymphoproliferative disease (20.0%, SIR 14.14, 95% CI: 9.45–22.04). Predictors of DNM following lung transplantation were age (hazard ratio [HR] 1.03, 95% CI: 1.02–1.05, p < 0.001), male gender (HR 1.20, 95% CI: 1.02–1.42, p = 0.03), disease etiology (not cystic fibrosis, idiopathic pulmonary fibrosis or interstitial lung disease, HR 0.59, 95% CI 0.37–0.97, p = 0.04) and single‐lung transplantation (HR 1.64, 95% CI: 1.34–2.01, p < 0.001). Significant interactions between donor or recipient smoking and single‐lung transplantation were noted. On multivariable survival analysis, DNMs were associated with an increased risk of mortality (HR 1.44, 95% CI: 1.10–1.88, p = 0.009).     

Preoperative prediction score of hepatocellular carcinoma recurrence in living donor liver transplantation: Validation of SNAPP score developed at Asan Medical Center

The previously proposed scoring systems are not readily available because of the lack of simplicity for predicting hepatocellular carcinoma (HCC) recurrence. We aimed to develop and validate the new score system, which can predict HCC recurrence after living donor liver transplantation (LDLT) by using morphologic and biologic data. Predictors for HCC recurrence after LDLT were developed (n = 627) and validated (n = 806) in 1433 patients for whom we could collect information to date between 2007 and 2016 at Asan Medical center (AMC) to create the SNAPP score (tumor S ize and N umber, alpha-fetoprotein [A FP], vitamin K absence-II [P IVKA-II], positron emission tomography [P ET]). On logistic regression based on 3-year recurrence-free survival, the SNAPP factors were independently associated with HCC recurrence. The SNAPP score was highly predictive of HCC recurrence (C statistic, 0.920), and 5-year post-LT recurrence rates were significantly different between low, intermediate, and high SNAPP score groups. The performance of the SNAPP score (C-index [95% confidence interval], 0.840 [0.801-0.876]) on predicting tumor recurrence after LDLT was better than that of the New York/California, the Risk Estimation of Tumor Recurrence After Transplant (RETREAT), and the Model of Recurrence After Liver Transplant (MoRAL) score. The SNAPP score provides excellent prognostication after LDLT for HCC patients. Hence, we can help voluntary patients’ decisions about whether to undergo LDLT or not.     

Liver transplantation and waitlist mortality for HCC and non‐HCC candidates following the 2015 HCC exception policy change

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non‐HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013‐2017 SRTR data, we identified 39  350 adult, first‐time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non‐HCC candidates before (October 8, 2013‐October 7, 2015, prepolicy) and after (October 8, 2015‐October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non‐HCC candidates with the same calculated MELD, HCC candidates had a 3.6‐fold higher rate of DDLT prepolicy (aHR = _3.49 3.69 _3.89) and a 2.2‐fold higher rate of DDLT postpolicy (aHR = _2.09 2.21 _2.34). Compared to non‐HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = _0.54 0.63 _0.73) and a comparable risk of mortality/dropout postpolicy (asHR = _0.81 0.95 _1.11). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest‐first liver allocation, the revised policy seems to have established allocation equity for HCC and non‐HCC candidates.     

Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation

Angiotensin II type I receptor (AT1R) agonistic autoantibodies (AT1R‐AA) are detrimental to kidney transplantation. Early studies suggested a similar negative effect in primary liver transplantation. Here, we studied AT1R‐AA in a retrospective cohort of 94 patients who received a second liver transplant to determine their prevalence and effects. The concentrations of preformed AT1R‐AA before transplantation were higher (P = .019) in the 48 patients who lost their liver grafts than in the 46 patients whose grafts survived. About half (48/94, 51.1%) of the patients were positive for AT1R‐AA >17 U/mL before the second liver transplantation. In 22 (23.4%) patients, strong positive AT1R‐AA (defined as >40 U/mL) were detected, of whom 16 (72.7%) patients lost their grafts. Based on Kaplan‐Meier analysis, patients with strong positive AT1R‐AA had significantly worse graft survival than those with AT1R‐AA <40 U/mL (P = .035). In multivariate Cox models that included confounders such as sex and age, either AT1R‐AA >40 U/mL (HR = 1.999 [1.085‐3.682], P = .026) or increased concentrations of AT1R‐AA (HR = 1.003 [1.001‐1.006] per incremental U/mL, P = .019) were significantly associated with elevated risk for graft loss. In conclusion, our data indicate that there is a high prevalence of AT1R‐AA in candidates for second liver transplantation and that their presence is associated with inferior long‐term outcomes of the second graft.     

Changing demographics of heart donors: The impact of donor drug intoxication on posttransplant survival

Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms. Recipients were propensity matched (drug‐intoxicated—non‐drug‐intoxicated = 1:2) and posttransplant survival was compared using Kaplan‐Meier curves. In total, 19 384 donor hearts were used for transplant during the period (donor age 31.6 ± 11.8 years, 72% male). Use of drug‐intoxicated donors increased from 2% (2005) to 13% (2015) and decreased from blunt injury (40%‐30%) and intracranial hemorrhage (29%‐25%). After propensity matching, posttransplant survival of drug‐intoxicated donor hearts was 90%, 82%, and 76% at 1, 3, and 5 years, which was similar to non‐drug‐intoxicated. Heart transplants using drug‐intoxicated donors have significantly increased; however, they have not adversely affected posttransplant survival. Hearts from drug‐intoxicated donors should be carefully evaluated and considered for transplant.     

Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: A systematic review

Solid organ transplant (SOT) is frequently complicated by cancers, which render immunosuppression challenging. Immune checkpoint inhibitors have emerged as treatments for many cancers. Data are lacking regarding efficacy and rejection risk in the SOT population. We conducted a systematic literature review and analyzed 83 cases of immune checkpoint inhibitor use for cancer in SOT. Two thirds of these patients received anti–programmed death ligand 1 therapy, 15.7% received anti–cytotoxic T lymphocyte–associated protein 4 therapy, and 10.8% received a combination. Allograft rejection occurred in 39.8% of patients, leading to end‐stage organ failure in 71.0% of cases. Outcomes were similar across organs and immunotherapy regimens. The use of immunosuppressants other than steroids, time since transplant, and prior episodes of rejection were associated with the risk of rejection. The median overall survival of patients was 36 weeks. Most of the deaths were related to cancer progression. In nonkidney recipients, graft rejection was strongly associated with worse survival. At the end of the study, 19.3% of the patients were alive, free from rejection and tumor progression. This study highlights the difficult tradeoff facing oncologists and transplant specialists managing transplant recipients with cancer, and the need for prospective data and novel biomarkers for identifying the patients likely to benefit from immunotherapy in the SOT setting.     

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single‐organ deceased‐donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non‐BCPD cohort. One‐year graft and patient survival were compared between cohorts using Kaplan–Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non‐BCPD. Graft survival was significantly lower in BCPD recipients compared to non‐BCPD recipients (Kaplan–Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity‐matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01–1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms.     

Enteric conversion after bladder‐drained pancreas transplantation is not associated with worse allograft survival

In the early experience of pancreas transplantation, bladder drainage was favored, but it often caused urologic, metabolic, and infectious complications that necessitated conversion to enteric drainage. Long‐term graft survival after enteric conversion and the impact of time interval from transplantation to enteric conversion on graft survival is poorly understood. We studied all bladder‐drained first‐time pancreas transplantations performed at the University of Wisconsin from 1985 to 2000. Time to conversion was estimated with the Kaplan‐Meier technique, whereas risk factors associated with conversion were estimated via a time‐varying Cox proportional hazards model. Of 386 bladder‐drained pancreata, 162 (41.9%) eventually required enteric conversion, 29 (17.9%) within the first year. Median time to conversion varied by indication: 0.68 years for surgical, 3.1 years for urologic, and 2.7 years for metabolic disorders. In a time‐varying Cox model adjusting for donor and recipient factors, enteric conversion did not affect the risk of pancreas graft loss (hazard ratio [HR] 0.86, P = .26). Kidney survival was not associated with enteric conversion. When necessary due to symptoms or complications, enteric conversion of bladder‐drained pancreata is safe and does not affect overall graft survival. This relationship appears to be true no matter when the conversion is performed.     

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.     

Validation of the “Metroticket” model in a cohort of patients transplanted for hepatocellular carcinoma in southern Brazil

This retrospective study evaluated the ability of the Metroticket model to predict five‐yr post‐transplant survival in patients with hepatocellular carcinoma (HCC) based only on explant data. Five‐yr survival after transplant was estimated using the Metroticket Calculator, and observed survival was calculated using the Kaplan–Meier method. Metroticket‐predicted survival was compared between deceased and surviving patients using the Mann–Whitney test. The accuracy of Metroticket estimates in discriminating between these two patient groups was assessed using the c‐statistic. Median patient age (n = 109) was 55.7 yr, and 72.5% of the sample were men. Metroticket‐predicted and observed post‐transplant survival at five yr was 71.1% and 58.7%, respectively. Predictions were calculated using the explant data of the 64 survivors and 45 deceased patients. Median five‐yr survival was 72.9% in the former and 69.7% in the latter. The c‐statistic of the Metroticket model for distinguishing surviving from deceased patients was 0.55. In this cohort, the Metroticket model was unable to accurately predict five‐yr post‐transplant survival based only on explant data.     

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.     

Impact of the new MELD‐based allocation system on waiting list and post‐transplant survival—a cohort analysis using the French national CRISTAL database

Concerns related to equity and efficacy of our previous center‐based allocation system have led us to introduce a patient‐based allocation system called the “Liver Score” that incorporates the model for end‐stage liver disease (MELD) score. The main objective of this study was to compare waitlist and post‐transplant survivals before and after implementation of the “Liver Score” using the French transplant registry (period before: 2004–2006 and period after: 2007–2012). Patients transplanted during the second period were sicker and had a higher MELD. One‐year waitlist survival (74% vs. 76%; P = 0.8) and 1‐year post‐transplant survival (86.3% vs. 85.7%; P = 0.5) were similar between the 2 periods. Cirrhotic recipients with MELD > 35 had lower 1‐year post‐transplant survival compared to those with MELD <35 (74.8% vs. 86.3%; P < 0.01), mainly explained by their higher intubation and renal failure rates. The MELD showed a poor discriminative capacity. In cirrhotic recipients with MELD > 35, patients presenting 2 or 3 risk factors (dialysis, intubation, or infection) had a lower 1‐year survival compared to those with none of these risk factors (61.2% vs. 92%; P < 0.01). The implementation of the MELD‐based allocation system has led to transplant sicker patients with no impact on waitlist and post‐transplant survivals. Nevertheless, selection of patients with MELD > 35 should be completed to allow safe transplantation.     

Risk of lip cancer after solid organ transplantation in the United States

Solid organ transplant recipients have an increased risk of lip cancer, but the reasons are uncertain. Using data from the Transplant Cancer Match Study, we describe the epidemiology of lip cancer among 261 500 transplant recipients in the United States. Two hundred thirty‐one lip cancers were identified, corresponding to elevated risks for both invasive and in situ lip cancers (standardized incidence ratios of 15.3 and 26.2, respectively). Invasive lip cancer incidence was associated with male sex (adjusted incidence rate ratio [aIRR] 2.01, 95% CI 1.44‐2.82), transplanted organ (0.33, 0.20‐0.57, for liver transplants and 3.07, 1.96‐4.81, for lung transplants, compared with kidney transplants), and racial/ethnic groups other than non‐Hispanic whites (0.09, 0.04‐0.2). In addition, incidence increased with age and during the first 3 years following transplant, and was higher in recipients prescribed cyclosporine/azathioprine maintenance therapy (aIRR 1.79, 95% CI 1.09‐2.93, compared with use of tacrolimus/mycophenolate mofetil) and following a diagnosis of cutaneous squamous cell carcinoma (4.21, 2.69‐0.94). The elevation in lip cancer incidence is consistent with an effect of immunosuppression. Notably, the very strong associations with white race and history of prior skin cancer point to an important role for ultraviolet radiation exposure, and cyclosporine and azathioprine may contribute as photosensitizing or DNA damaging agents.