Organ transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged immunosuppression associated with organ grafting. The purpose of this study is to determine risk factors, clinical characteristics, and outcomes of de novo nonlymphoid malignancies after liver transplantation from a large single-center series. All patients undergoing liver transplantation at the King's College Hospital (London, UK) between January 1988 and December 1999 were analyzed retrospectively for the development of de novo malignancy in the posttransplantation period. Records were evaluated for age at diagnosis of malignancy, cause of liver disease, interval from transplantation to diagnosis of malignancy, predisposing factors for the development of cancer, immunosuppression regimen, treatment of malignancy, rejection episodes, and patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30 patients (2.6%) developed de novo nonlymphoid malignancy after transplantation. Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n = 2), and various other malignancies (n = 9). The mean time of presentation of the malignancy after transplantation was 45.1 +. 32 months (range, 6 to 133 months), and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The incidence of de novo malignancy was significantly greater in patients who underwent transplantation for alcoholic liver disease compared with other groups (P < .001). Although the incidence of de novo nonlymphoid malignancy after liver transplantation is low, patients who underwent transplantation for alcoholic cirrhosis appear to have an increased risk for developing posttransplantation malignancy. (Liver Transpl2002;8:482-48%) 0 rgan transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged, often lifelong, immunosuppression

Background The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival.Methods New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m² administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m² administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m² repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m² administered intravenously over 2 h and oral capecitabine 1000 mg/m² twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m² intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m² every 2 weeks with regimen one and three or a loading dose of 400 mg/m² followed by a weekly infusion of 250 mg/m² with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-totreat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367.

Budd-Chiari Syndrome (BCS) is a group of disorders resulting from obstruction to hepatic venous outflow; myeloproliferative disorder (MPD) accounts for 10–40% of cases. A number of BCS cases labelled as ‘idiopathic’ do not fulfil the accepted diagnostic criteria for MPD but have features suggestive of a latent form of MPD based on hyperplastic bone marrow and spontaneous erythroid colony progenitor cell culture studies; these cases may subsequently develop overt MPD. A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of potential use in the characterization of latent MPD in BCS. We studied 44 patients with BCS (female n=27, mean age 36.1 years, SD 13) presenting between 1985 and 2005. Genomic DNA obtained from archived bone marrow films was screened by allele-specific PCR for the JAK2V617F tyrosine kinase mutation. JAK2V617F was detected in 27/44 (61.4%) subjects. Fulminant hepatic failure was the presenting feature in 86.4%. 3/38 subjects had previously diagnosed Polycythemia Vera and all of these were JAK2V617F positive. Analysis for hereditary thrombophilia in 32/44 cases showed Factor V Leiden (FVL) heterozygosity (n=2) and Protein C deficiency (n=1); JAK2V617F was detected in one of the FVL cases. Screening for antiphospholipid antibodies and paroxysmal nocturnal hemoglobinuria in 31 and 30 out of 44 cases respectively proved negative. 22/44 cases had splenomegaly of which 72.2% had JAK2V617F detected. Mean hemoglobin concentration was higher in patients with JAK2V617F (12.4 g/dL, SD 2.8) compared to the wild-type allele (10.2 g/dL, SD 2.1)(p=0.005). Mean neutrophil count was similar (p=0.26) in both groups (JAK2V617F 7.8 x109/L, SD 5.5; wild-type 6.1 x109/L, SD 4.5). Mean platelet count was higher (p=0.01) in subjects with JAK2V617F (289 x109/L, SD 192) compared to wild-type (180 x109/L, SD 158). The bone marrow (BM) was hyperplastic in all lineages in 19/44 subjects of which 15 (78.9%) contained the JAK2V617F mutation. Importantly, in 25/44 subjects without hyperplastic BM, 48% had JAK2V617F detected. Clonal cytogenetic abnormalities occurred in 6/44 subjects all of which carried JAK2V617F. In 35 evaluable subjects, 10/35 (28.6%) showed endogenous erythroid colony (EEC) formation (8/10 JAK2V617F positive), and the remainder (25/35) showed no EEC formation (14/25 JAK2V617F positive). Treatment of BCS included anticoagulation (n=44), porto-systemic shunt insertion (n=26) and orthotopic liver transplantation (OLT) (n=15). Overall survival was 81.8% (median 32.5 months, range 2 days-240 months). In the 8 non-survivors, JAK2V617F was detected in 50%. 15/44 subjects underwent OLT (11/15 JAK2V617F positive) of which 14/15 are alive at a median of 36 months post transplant (1–240 months). 14/44 subjects were treated with cytoreductive treatment following diagnosis of BCS and in 92.9% of these JAK2V617F was detected. 5/15 subjects went on to receive cytoreductive treatment following OLT of which all were JAK2V617F positive. We have found a high prevalence of JAK2V617F in patients with BCS. Latent MPD was missed in 12/25 subjects on BM morphology and 14/25 subjects on BM progenitor culture. We suggest that JAK2V617F analysis should be performed in all new cases of BCS. Given their age, these patients are possible candidates for JAK2 targeted therapy.

Achieving clear microscopic resection margins following pancreaticoduodenectomy (PD) is challenging particularly in borderline resectable pancreatic carcinoma (BRPC). Positive resection margins has been identified as a major independent prognostic factor. Irreversible electroporation (IRE) has emerged as a promising non-thermal ablative method that could be used in the treatment of pancreatic cancer as an adjunct to chemotherapy and surgery. This case report describes the successful simultaneous intraoperative IRE and PD in a patient with BRPC, achieving clear microscopic resection margins. Technical aspects and histology showing the effect of IRE are presented. The role of IRE in the treatment of pancreatic adenocarcinoma should be further evaluated in prospective studies.

Hepatitis C virus (HCV) is a major health problem that leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma, being the most frequent indication for liver transplantation in several countries. Unfortunately, HCV re-infects the liver graft almost invariably following reperfusion, with an accelerated history of recurrence, leading to 10%-30% of patients progressing to cirrhosis within 5 years of transplantation. In this sense, some groups have even advocated for not retransplanting this patients, as lower patient and graft outcomes have been reported. However, the management of HCV recurrence is being optimized and several strategies to reduce post-transplant recurrence could improve outcomes, decrease the rate of re-transplantation and optimize the use of available grafts. Three moments may be the focus of potential actions in order to decrease the impact of viral recurrence: the pretransplant moment, the transplant environment and the post-transplant management. In the pre-transplant setting, it is not well established if reducing the pre transplant viral load affects the risk for HCV progression after transplant. Obviously, antiviral treatment can render the patient HCV RNA negative post transplant but the long-term benefit has not yet been fully established to justify the cost and clinical risk. In the transplant moment, factors as donor age, cold ischemia time, graft steatosis and ischemia/reperfusion injury may lead to a higher and more aggressive viral recurrence. After the transplant, discussion about immunosuppression and the moment to start the treatment (prophylactic, pre-emptive or once-confirmed) together with new antiviral drugs are of interest. This review aims to help clinicians have a global overview of posttransplant HCV recurrence and strategies to reduce its impact on our patients.