De Novo Cancers Research Articles

A101 BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM OCCURRING POST-LIVER TRANSPLANT FOR PSC WITH CLINICAL REMISSION OF ULCERATIVE COLITIS AFTER STEM CELL TRANSPLANTATION

BackgroundPrimary sclerosing cholangitis (PSC) is a rare autoimmune fibroinflammatory disease that is associated with inflammatory bowel disease (IBD) and can progress to end-stage liver disease (ESLD) requiring liver transplantation (LT). Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a highly aggressive and rare hematologic malignancy (HM) that usually affects elderly males. High-dose chemotherapy followed by allogenic stem cell transplantation (SCT) offers the best chance of long-term remission in BPDCN. While it is well described that there is an increased risk of de-novo cancer development after solid organ transplantation (SOT), these are less commonly HMs. There are currently no documented cases of BPDCN in post-SOT patients in the literature.AimsTo describe one of the first cases of BPDCN in a patient post-SOT, and subsequent clinical resolution of UC post SCT.MethodsCase ReportResultsA 19-year-old previously healthy male initially presented with cholangitis and was diagnosed with PSC. Two years after the diagnosis of PSC, he progressed to ESLD and underwent live donor LT in India. He subsequently presented with episodes of bloody diarrhea and a colonoscopy then revealed diffuse mucosal edema, erosions, and spontaneous bleeding, with scattered inflammatory polyps throughout the colon. UC was diagnosed and Infliximab therapy was started. He later presented with a UC flare and Vedolizumab therapy was initiated. A liver biopsy showed recurrent sclerosing cholangitis and ultimately the patient required a second liver transplant. After the second LT he developed weight loss, arthralgias, and progressive splenomegaly following which BPCDN was diagnosed. His Vedolizumab was subsequently stopped. He received induction chemotherapy followed by a single antigen mismatched allogenic SCT. Whilst he had numerous complications associated with his chemotherapy induction, his UC appeared to be in clinical remission. No repeat colonoscopies were completed, however, on follow-up assessments, he denied abdominal pain and reported having formed, non-bloody stools. Unfortunately, he suffered an aggressive relapse of his BPCDN, and he was palliated.ConclusionsThe development of de-novo cancers after LT is common, and patients with PSC are at particularly high risk. PSC-LT patients have also been found to have the highest rate of hematological malignancies post LT; however, these are most commonly post-transplant lymphoproliferative disorder. Additionally, there have been a few reports of complete resolution of IBD after allogenic mismatched SCT. Here we describe one of the first cases of BPCDN post-LT in a PSC-UC patient and display another example of UC clinical remission post allogenic SCT. These findings emphasize that close follow-up of these patients after LT is imperative.Funding AgenciesNone

Clinical outcomes and temporal trends of immunological and non-immunological rare diseases in adult kidney transplant

BackgroundRare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs.MethodsRetrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT).ResultsAmong 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8–11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups.ConclusionsKidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients’ and graft survival.

P1692CANCER-RELATED EPIDEMIOLOGY AND OUTCOMES IN KIDNEY ALLOGRAFT RECIPIENTS FROM TWO TRANSPLANT CENTRES IN ITALY

Abstract Background and Aims One of the major immunosuppression-related complications of kidney transplant (KT) is the increased risk of cancer development. KT patients have at least a twofold higher risk of developing or dying from cancer than the general population. Indeed, malignancy is currently the second most common cause of death after cardiovascular disease in these patients. After the substantial rise in post-transplant graft survival in the last decades, the present study aims to evaluate the post–KT cancer incidence, the mortality risk and associated risk factors in two transplant centres over a long period of time. Method A retrospective cohort study used clinical and epidemiological information among KT patients transplanted between 1993 and 2017 in two renal transplant centres in Italy and diagnosed with de novo cancers (DNC). Data on vital status and graft loss were available for most subjects and assessed in December 2019. Survival analyses were performed using parametric survival models assuming a Weibull distribution of the baseline hazard; these models were used to test the association between predictors measured at baseline and a) time from KT to development of DNC, and b) time from development of DNC to death, loss to follow-up or administrative censoring, whichever occurred first. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained. Kaplan–Meier curves were generated. A p-value < 0.05 was considered as statistically significant. Data were analyzed using Stata. Results In the present study, 201 DNCs were diagnosed in subjects who underwent KT between 1993 and 2017. Median follow-up after kidney transplantation was 12.1 years (IQR: 7.0–17.5). The proportion of subjects who received allograft from deceased donor was 89%, 61% had 4 or more mismatches, 68% were male. At the time of KT, the average age was 52.4±12.3 years and renal replacement therapy (RRT) vintage was 39 months (IQR: 22–69). The incidence rate of DNC for the whole cohort was 145 per 1,000 person-years, with a median time to cancer from KT of 5.5 years (IQR: 2.8–10.5) [Figure 1]. Skin cancers accounted for most cases (59%), followed by solid tumors (30%), post-transplant lymphoproliferative disorders (6%), Kaposi’s sarcoma (3%) and other malignancies (2%). In the multivariable model, increasing age was significantly associated with time to development of DNC (HR for 1 year 1.03, 95% CI 1.01, 1.04; p = 0.001). Induction therapy with a combination of rabbit antithymocyte globulin and basiliximab resulted to be a risk factor for time to DNC (HR compared with none 3.16, 95% CI 2.04, 4.91; p < 0.001). None of the following pre- and peri-transplant predictors was significantly associated with time to DNC: RRT vintage and technique, episodes of acute rejection, chronic kidney disease etiology, presence of delayed graft function, type of donor (deceased or living), number of mismatches. The incidence rate of death for the whole cohort was 47 per 1,000 person-years [Figure 2]. According to type of cancer, death incidence rate was 73, 56, 34 per 1,000 person-years for solid tumors, non-solid and non-skin tumors (i.e PTLD, Kaposi and other tumors) and skin cancer, respectively. In multivariable analysis, age at time of cancer (HR for 1 year 1.04, 95% CI 1.00, 1.07; p = 0.037) and previous acute rejection (HR 2.51, 95% CI 1.23, 5.11; p = 0.011) were significantly associated with time to death. Conclusion In a large sample of KT recipients with DNC, age and type of induction therapy were significantly associated with time to development of cancer. Age and previous acute rejection were significant predictors of death after DNC. Epidemiological studies could help in risk estimation of graft and patient survival after cancer development and guide in post KT clinical care.

Versatility of Pectoralis Major Myocutaneous Flap for Reconstruction of Large Oral Cavity Defects

Abstract Background: Oral cavity reconstruction is one of the most challenging and progressive areas in reconstructive surgery. In oral cavity reconstruction the main goals are prompt and safe restoration of mucosal integrity, avoid oro-cutanoeus fistula with restoration of the bony support whenever needed, followed by restoration of the function then lastly restoration of the form (aesthetics). Aim of Study: The aim of our study is to evaluate the feasibility of using pectoralis major muscle myocutaneous flap in reconstruction of oral cancer post excision defects. Patients and Methods: This is a retrospective study in which sixteen patients with oral cavity malignant tumors underwent surgical excision and immediate reconstruction, during the period from July 2016 to July 2019 with pectoralis major myocutaneus flap as regard peri operative evaluation and post operative complications. Results: This retrospective study included 16 patients with oral malignancy with reconstruction of the oral defect using pectoralis major myocutaneous flap. The mean duration of follow-up in all patients was 13.8 months (ranged from 6 to 30 months). From 16 patients, 4 patients (25%) patients had De-novo cancers, while the rest were recurrent cases. Conclusion: Pectoralis major myocutaneous flap is considered as an easy, simple method in cases of large oral cavity defects. It can be used as a back up or an alternative to free tissue transfer or even as salvage procedure.

De Novo Cancer Incidence and Prognosis After Kidney Transplantation: A Single Center Analysis

BackgroundMalignancy is an important cause of mortality in renal transplants recipients. The aim of this study was to evaluate the incidence, prognosis, and survival of patients developing a de novo post-transplant cancer. MethodsUsing a retrospective cohort design, we evaluated the incidence of de novo cancers among kidney transplants patients in our hospital from January 2000 to December 2012. We also evaluated the patient survival after tumor diagnosis. ResultsWe included 535 kidney transplants recipients with a mean follow-up of 7.8 years; among them, 39 (7.2%) developed malignancies. Median time from transplant to cancer diagnosis was 3 years, with a median age at diagnosis of 60 years. Male patients were significantly older at time of cancer diagnosis (68.5 years) compared with women (38 years, P < .05), and cancer diagnosis occurred significantly earlier in men (3.5 years since transplantation) than in women (8.5 years, P < .05). Among 39 patients affected by a de novo post-transplant cancer, 18 patients (46.2%) died, with an average age at death of 58.5 years. The average time from cancer diagnosis to death was 1.5 years. Among the group of patients who did not develop a post-transplant cancer, 83 patients (16.7%) died, with a median age at time of death of 54.5 years (P < .05). ConclusionsKidney transplant recipients are at higher risk of developing a post-transplant cancer. Prognosis after cancer diagnosis is poor, probably as a consequence of a more aggressive behavior of cancer in transplant recipients. Intensive screening protocols could allow for an earlier diagnosis thereby improving the long-term outcome of these patients.

Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis.

Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT. All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT. Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy. The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.

Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

BackgroundDe novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear.AimsTo describe the overall pattern of de novo cancers in liver transplant recipients.MethodsData from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies.ResultsAmong 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation.ConclusionsDe novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

The Spectrum of De-Novo Cancers After Kidney or Liver Transplant in Southern Europe: Evidence From a Multicentre Longitudinal Investigation in Ital.

The Spectrum of De-Novo Cancers After Kidney or Liver Transplant in Southern Europe: Evidence From a Multicentre Longitudinal Investigation in Ital.

De Novo Malignancies After Organ Transplantation: Focus on Viral Infections

Organ transplantation is an increasingly used medical procedure for treating otherwise fatal end stage organ diseases with 107,000 transplants performed worldwide in 2010. Newly developed anti-rejection drugs greatly helped to prolong long-term survival of both the individual and the transplanted organ, and they facilitate the diffusion of organ transplantation. Presently, 5-year patient survival rates are around 90% after kidney transplant and 70% after liver transplant. However, the prolonged chronic use of immunosuppressive drugs is well known to increase the risks of opportunistic diseases, particularly infections and virus-related malignancies. Although transplant recipients experience a nearly 2-fold elevated risk for all types of de-novo cancers, persistent infections with oncogenic viruses - such as Kaposi sarcoma herpes virus, high-risk human papillomaviruses, and Epstein-Barr virus - are associated with up to 100-fold increased cancer risks. This review, focusing on kidney and liver transplants, highlights updated evidences linking iatrogenic immunosuppression, persistent infections with oncogenic viruses and cancer risk. The implicit capacity of oncogenic viruses to immortalise infected cells by disrupting the cell-cycle control can lead, in a setting of induced lowered immune surveillance, to tumorigenesis and this ability is thought to closely correlate with cumulative exposure to immunosuppressive drugs. Mechanisms underlying the relationship between viral infections, immunosuppressive drugs and the risk of skin cancers, post-transplant lymphoproliferative disorders, Kaposi sarcoma, cervical and other ano-genital cancers are reviewed in details.

Risk of de novo cancers after transplantation: Results from a cohort of 7217 kidney transplant recipients, Italy 1997–2009

To assess incidence and risk factors for de novo cancers (DNCs) after kidney transplant (KT), we carried out a cohort investigation in 15 Italian KT centres.Seven thousand two-hundred seventeen KT recipients (64.2% men), transplanted between 1997 and 2007 and followed-up until 2009, represented the study group. Person years (PY) were computed from 30days after transplant to cancer diagnosis, death, return to dialysis or to study closure. The number of observed DNCs was compared to that expected in the general population of Italy through standardised incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed.Three-hundred ninety five DNCs were diagnosed during 39.598PYs, with Kaposi’s sarcoma (KS), post-transplant lymphoproliferative disorders (PTLD), particularly non-Hodgkin’ lymphoma (NHL), lung, kidney and prostate as the most common types. The overall IR was 9.98/1.000PY, with a 1.7-fold augmented SIR (95% CI: 1.6-1.9). SIRs were particularly elevated for KS (135), lip (9.4), kidney carcinoma (4.9), NHL (4.5) and mesothelioma (4.2). KT recipients born in Southern Italy were at reduced risk of kidney cancer and solid tumors, though at a higher KS risk, than those born in Northern Italy. Use of mTOR inhibitors (mTORi) exerted, for all cancers combined, a 46% significantly reduced risk (95% CI: 0.4–0.7).Our study findings confirmed, in Italy, the increased risks for cancer following KT, and they also suggested a possible protective effect of mTORi in reducing the frequency of post transplant cancers.

Interferon Therapy and Prevention of Hepatocellular Carcinoma in Hepatitis C

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and one of the leading causes of death among patients with cirrhosis. Its incidence is expected to continue increasing over the next 20 years and to peak around 2030 [1]. Although hepatitis B remains the most common risk factor worldwide, chronic hepatitis C virus (HCV) infection is the driving force for the increased incidence of HCC in Western countries and Japan [1]. Therefore, strategies aimed at eliminating the virus may provide opportunities for primary and secondary prevention of the development of HCC. The first evidence of primary prevention of HCC was from a small randomized controlled trial with 90 HCVinfected patients in which interferon (IFN) treatment was associated with a significant reduction in the incidence of HCC [2]. The beneficial effects of IFN therapy were thought to be related to its anti-proliferative, anti-angiogenic, and/or anti-tumor effects [3, 4]. Since that time, several studies have replicated the findings of a reduction in HCC risk among patients treated with IFN, particularly patients who achieved a sustained viral response (SVR). A meta-analysis found that SVR was associated with a 79% (95% CI 0.73–0.84) reduction in the risk of development of HCC by patients with HCV-related cirrhosis [5]. The primary preventive effect of IFN therapy may be even greater among non-cirrhotic HCV patients, given that SVR at earlier stages of fibrosis can prevent the development of cirrhosis. Given that the effect of IFN therapy was primarily seen among patients who had SVR, the utility of maintenance pegylated interferon (PEG–IFN) to prevent disease progression and HCC among non-responders was evaluated. Several randomized trials (HALT-C, COPILOT, and EPIC) have since demonstrated that maintenance PEG–IFN fails to prevent HCC in patients with HCV-related cirrhosis among non-responders [6–8]. Patients with HCC who are diagnosed at an early stage can be effectively treated by liver transplantation, surgical resection, or local ablative therapy [9]. Although liver transplantation effectively treats both the HCC and replaces the underlying cirrhotic liver, it is not possible for all patients, given rigorous selection criteria and a shortage of organs. Surgical resection and local ablative therapy are able to achieve high cure rates, but these patients remain at high risk of developing recurrent or de-novo cancers. Recurrence 5 years after resection of primary tumors is reported to be approximately 50% [10]. Early recurrence seems to be primarily driven by metastases and is associated with factors such as microvascular invasion and AFP level. Late recurrence, i.e., that occurring after 2 years, often appears as de-novo lesions and is associated with factors such as hepatitis activity and persistent HCV viremia [11]. Given the widespread implementation of HCC surveillance programs and increasing burden of HCC, a greater proportion of patients is expected to be diagnosed during early stages and be suitable for either resection or local ablation. Given the associated high incidence of recurrent or de-novo tumors, further studies that address prevention of HCC recurrence are crucial. Several studies, including five randomized controlled trials and subsequent meta-analysis, have demonstrated A. G. Singal Division of Digestive and Liver Diseases, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA

Outcome of liver transplantion in recipients older than 65 years: A single center experience

Advanced age was considered a relative contraindication for liver transplantation (LT) in the past. The percentage of older patients referred for LT assessment has markedly increased in almost all LT centers over the last years. The data regarding the outcome of older patients have been contradictory. Therefore, we aimed to evaluate the long-term survival of LT recipients older than 65 years. Between 1982 and 2008, 106 out of 1011 patients (10.5%), who underwent LT at our institution, were older than 65 years. Almost all of these patients were transplanted after 1995. The mean age was 67.5 (65.0–76.4) years and the majority of patients were male (76%). Regarding underlying liver disease the percentage of non-alcoholic steatohepatitis associated cirrhosis was significantly higher in the older age group (15.9% vs. 5.8%, p<0.01) compared to the younger LT cohort. In contrast, alcoholic liver disease was more common in recipients under 65 years (20.4% vs. 14.1%, p<0.01). Significantly more patients in the older group presented with a concomitant hepatocellular carcinoma (40.6% vs. 23.7%, p<0.01). Both groups did not differ with regard to Child-Pugh classification and mean MELD score. The median follow-up of the older patients was 3.2 compared to 5.7 years of the younger cohort. The actuarial patient survival rates at 1-, 5- and 10-years with 85%, 65% and 56% were slightly lower in the older recipients compared to 87%, 75% and 66% of recipients ≤65 years. The major causes of death in the elderly were sepsis (n=13) in the early postoperative period and de-novo cancer (n=6), HCV/HCC recurrence (each n=5) and cardiovascular complications (n=4) in the late one. The incidence of de-novo cancers and cardiovascular diseases were significantly higher in the older age cohort. The percentage of reLTs did not differ between both groups (7.8% vs. 6.5%). Although overall survival was better for younger patients, this study shows that LT recipients older than 65 years have a favourable outcome after LT with a 5- and 10-year survival of 65% and 56%, indicating that liver transplantation should be considered in patients older than 65 years.

De Novo Cancers Arising in Organ Transplant Recipients are Associated With Adverse Outcomes Compared With the General Population

Transplant recipients are at increased risk of malignancy; however, the influence of transplantation on cancer outcomes has not been rigorously defined. The purpose of this study was to examine the influence of transplantation on the outcomes of individual cancers. De novo nonsmall cell lung cancer, colon cancer, breast cancer, prostate cancer, bladder cancer, renal cell cancer (RCC), and malignant melanoma data in 635 adult (>18 years of age) transplant recipients (from the Israel Penn International Transplant Tumor Registry) were compared with data from 1,282,984 adults in the general population (from the Surveillance, Epidemiology, and End Results database). Compared with the general population, transplant patients were more likely to have early stage (AJCC stage 0-II) RCC, but more advanced (AJCC stage >II) colon cancer, breast cancer, bladder cancer, and malignant melanoma. Compared with the general population, disease-specific survival was worse in the transplant population for colon cancer (all stages), nonsmall cell lung cancer (stage II), breast cancer (stage III), prostate cancer (stage II, III, and IV), bladder cancer (stage III), and RCC (stage IV). Multivariate analyses demonstrated transplantation to be a negative risk factor for survival for each cancer studied, and transplantation and cancer stage at diagnosis to be the most profound negative survival predictors. These analyses indicate that, for several common cancers, transplant patients experience worse outcomes than the general population. The data also suggest that cancers in transplant recipients are more aggressive biologically at the time of diagnosis.

Proportion of De Novo Cancers Among Colorectal Cancers in Japan

Adenomatous polyps are main precursors of colorectal cancers (CRCs). In Japan, de novo cancers, which do not arise from preexisting adenomas, are considered to account for a substantial number of CRCs, but the relative importance of de novo carcinogenesis remains controversial. This study estimated the proportion of de novo cancers among CRCs in Japan. The subjects were persons 40-79 years of age who were relatively similar to those in the general population. The subjects underwent colonoscopy between 1997 and 2001. Early cancers among CRCs detected in this study were classified as de novo cancers or polyp cancers derived from adenomas. The age-specific incidence of the early CRCs was calculated, and the proportion of de novo cancers was estimated. The lifetime risk of early CRCs was estimated. The study group comprised 14,817 persons. CRCs were diagnosed in 189 subjects, including 83 early cancers. There were no differences with regard to size and location between de novo cancers and polyp cancers, but morphology differed. Eighty-four percent (16/19) of de novo cancers were flat elevated or depressed. The expected lifetime risk of developing early CRCs was 5.27% for men and 3.21% for women. Among persons with early cancers, the expected probabilities of developing de novo cancer were 18.6% for men, 27.4% for women. De novo cancers account for a considerable proportion in Japan. This information suggests that the recommended interval for colonoscopic examination in Japan should be shorter than that in the United States.

LONG TERM RESULTS OF LIVER TRANSPLANTATION FOR ALCOHOLIC RELATED LIVER DISEASE UNDER TACROLIMUS

765 Results of liver transplantation (Ltx) for alcohol related liver disease have been quite satisfactory in short term. Aim of the present study is to examine the results of patient/graft survival and evaluate the causes of graft loss and death in long term. Material: Between Sept. 89 and Dec. 92, 188 adults received primary Ltx under tacrolimus for alcoholic related end stage liver disease. These were 132 (70%) male and 56 (30%) female; mean age 51.0±10.1 (median 51.5; range 25.9 to 75.0) 31 (16%) patients had associated other diagnosis (13-non A non B hepatitis, 10- hepatocellular carcinoma, 4 - autoimmune hepatitis, 3 hepatic B and 1 - cholangiocarcinoma). All patients were followed until April 98. Mean follow-up 7.1 ± 0.9 (mean 7.2; range 5.4 to 8.6) years. 96 (51% were 1 cu bound (UNOS 2A 67 (35.6%) non ICU bound hospitalized (UNOS 2B) and 25 (13.3%) patients came from home (UNOS-3). Results: During the follow up period 23 patients received second Ltx (hepatic artery thrombosis 12, primary non-function 8, portal vein thrombosis, biliary stricture 1, HCV - 1,) and 3 patients received 3rd Ltx. 77 patients died. Commonest cause of late death was denovo cancers accounted 10 cases; 13% of all deaths and 28, 9% of deaths beyond 2 years. (Oropharyngeal - 5, lung - 3, renal -1, unknown primary -1). Patient and graft survival for different UNOS status is shown in the (table). Rate of recidivism is currently evaluated.TableConclusion: overall patients survival and graft survival in long term for alcoholic related end stage liver disease has remained satisfactory with 7 year patient survival of 60% and graft survival of 57%. Rate of recidivism leading to graft loss has fortunately remained low because of prior rehabilitation. Commonest cause of late death, beyond two years, is denovo cancer (mainly oropharyngeal and pulmonary) and demands thorough screening for early detection to improve long term survival.