One hundred ninety-seven patients received anti-T-lymphocyte globulins Fresenius, mycophenolate mofetil and delayed cyclosporine, and were randomized to ≥6-month corticosteroids (+CS; n=99) or no CS (-CS; n=98). One- and five-year actual graft survival (censored for death) was 93.2% and 86.4% in the +CS group versus 94.9% and 89.8% in the -CS group (5-year follow-up, p=0.487). Freedom from clinical rejection was 86.9% and 81.8% versus 74.5% and 74.5% (p=0.144), respectively, at 1 and 5 years; 5-year freedom from biopsy-proven rejection was 88.9% versus 83.7% (p=0.227). More late first rejections occurred in the +CS group. Significantly lower 5-year graft survival in patients experiencing rejection was observed for +CS (55.6% vs. 92.0%; p=0.005) with 8/18 versus 2/25 graft losses. Renal function at 5 years was stable and comparable (median serum creatinine, 159 vs. 145 µmol/L; creatinine clearance, 53.5 vs. 56.6 mL/min). More +CS patients developed diabetes, dyslipidemia and malignancies. Rejections in -CS patients occurred early after transplantation and did not impair long-term renal function. In patients receiving CS, rejections occurred later and with a higher risk for subsequent graft failure. A similar and not inferior 5-year efficacy profile and a reduced morbidity were observed in CS-free patients compared to patients who received CS for at least 6 months.

Hepatic artery (HA) rupture after liver transplantation is a rare complication with high mortality. This study aimed to review the different managements of HA rupture and their results. From 1997 to 2007, data from six transplant centers were reviewed. Of 2649 recipients, 17 (0.64%) presented with HA rupture 29 days (2–92) after transplantation. Initial management was HA ligation in 10 patients, reanastomosis in three, aorto‐hepatic grafting in two and percutaneous arterial embolization in one. One patient died before any treatment could be initiated. Concomitant biliary leak was present in seven patients and could be subsequently treated by percutaneous and/or endoscopic approaches in four patients. Early mortality was not observed in patients with HA ligation and occurred in 83% of patients receiving any other treatment. After a median follow‐up of 70 months, 10 patients died (4 after retransplantation), and 7 patients were alive without retransplantation (including 6 with HA ligation). HA ligation was associated with better 3‐year survival (80% vs. 14%; p = 0.002). Despite its potential consequences on the biliary tract, HA ligation should be considered as a reasonable option in the initial management for HA rupture after liver transplantation. Unexpectedly, retransplantation was not always necessary after HA ligation in this series.

Background and Aims:The clinical application of a bioartificial liver (BAL) depends on the availability of a human cell source with high hepatic functionality.The human hepatoma cell line HepaRG has a unique high hepatic functionality in monolayer culture.Characteristics of the HepaRG cells cultured in the AMC-BAL over time were compared with those in monolayer cultures.Methods: HepaRG cells were cultured in laboratory-scale AMC-BALs for 21 days.14-Day-old HepaRG-AMC-BALs were studied by immunohistochemistry. Hepatic functionality was studied at 7, 14, and 21 days.Functional parameters included ammonia elimination, urea production, conversion of 15 N-ammonia into 15 N-urea, 6b-hydroxylation of testosterone (cytochrome P450 3A4 activity), lactate metabolism, and apolipoprotein A1 production.Next, 14-day-old HepaRG-AMC-BALs were compared with 28-dayold monolayer HepaRG cultures for the same protein-normalized functional parameters, cell leakage (lactate dehydrogenase and aspartate aminotransferase), transcript levels of various hepatic genes, and amino acid metabolism.Results: Immunohistochemistry of 14-day-old BALs demonstrated functional heterogeneity similar to that of monolayer cultures, Hepatic functionality of the HepaRG-AMC-BALs increased during 2-3 weeks of culture.The majority of the measured proteinnormalized hepatic functions were higher in day 14 BAL cultures compared to monolayer cultures, including ammonia elimination (3.2-fold), urea production (1.5-fold), conversion of 15 N-ammonia into 15 N-urea (1.4-fold), and cytochrome P450 3A4 activity (7.9fold).Lactate production in monolayer cultures switched into lactate elimination in the BALs, which is a hallmark of primary hepatocytes.Cell damage was 4-fold lower in 14-day-old BALs compared to monolayer cultures.In BAL cultures, transcript levels of cytochrome P450 1A2, 2B6, 3A4 and 3A7 genes and of the regulatory genes hepatic nuclear factor 4a and pregnane X receptor increased over time and were markedly higher than in monolayer cultures.In addition amino acid metabolism of HepaRG-AMC-BALs more resembled that of primary hepatocytes than monolayer HepaRG cultures.Conclusions: BAL culture of HepaRG cells increases its hepatic functionality both over time as well as compared to monolayer.This is associated with a reduction in cell damage, upregulation of both regulatory and structural hepatic genes, and changes in amino-acid metabolism.These results confirm the high potential of HepaRG cells for BAL application.

L’histoire de l’humanité foisonne en empoisonnements tentés ou réussis, par administration à autrui de substances toxiques ou vénéneuses variées. Cette observation récente est riche en enseignements tant sur le choix du toxique utilisé que sur les limites du diagnostic médical et l’impunité des assassins.Successful or attempted poisonings are abundant in human history. Various toxic or harmful substances were administered to the victims. The interest of this recent case-report regards not only the choice of poison but also the limits of medical diagnosis tools as well as murderers’ persistent impunity.

Background Hepatocellular carcinoma (HCC) is an indication for liver resection or transplantation (LT). In most centers, patients whose HCC meets the Milan criteria are considered for LT. The first objective of this study was to analyze whether there is a correlation between the pathologic characteristics of the tumor, survival and recurrence rate. Second, we focused our attention on vascular invasion (VI). Methods From January 1997 to December 2007, a total of 196 patients who had a preoperative diagnosis of HCC were included. The selection criteria for LT satisfied both the Milan and the San Francisco criteria (UCSF). Demographic, clinical, and pathologic information were recorded. Results HCC was confirmed in 168 patients (85.7%). The median follow-up was 74 months. The pathologic findings showed that 106 patients (54.1%) satisfied the Milan criteria, 134 (68.4%) the UCSF criteria of whom 28 (14.3%) were beyond the Milan criteria but within the UCSF criteria, and 34 (17.3%) beyond the UCSF criteria. VI was detected in 41 patients (24%). The 1-, 3-, and 5-year overall survival rates were 90%, 85%, and 77%, respectively, according to the Milan criteria and 90%, 83%, and 76%, respectively, according to the UCSF criteria ( P = NS). In univariate and multivariate analyses, tumor size and VI were significant prognostic factors affecting survival ( P < 0.001). Two factors were significantly associated with VI: alfa-fetoprotein level of >400 ng/ml and tumor grade G3. Conclusions Tumor size and VI were the only significant prognostic factors affecting survival of HCC patients. Primary liver resection could be a potential selection treatment before LT.

INTRODUCTION:Today local anesthetic wound infiltration is widely recognized as a useful adjunct in a multimodality approach to postoperative pain management. The effectiveness of continuous wound infusion of ropivacaine for postoperative pain relief after laparoscopic living donor nephrectomy was analyzed in this retrospective, comparative analysis.METHODS:Twenty patients undergoing living donor nephrectomy were divided into two groups: standard analgesic therapy (n=10) and ropivacaine continuous infusion group (n = 10).RESULTS:We observed a significant difference in term of visual analogue scale scores, use of morphine, hospital stay, and bowel recovery in favor of the ropivacaine group. The cost analysis demonstrated an overall savings of 985 Euros/patient.DISCUSSION:Surgical wound infusion with ropivacaine was safe and seemed to improve pain relief and accelerate recovery and discharge, reducing the overall costs of care. Postoperative pain control in the donor is of primary importance for better patient compliance and greater perceived quality of health care service.

Introduction. Sirolimus is a potent immunosuppressant with a mechanism of action different from calcineurin inhibitors (CNIs). It has increasing importance for liver transplant (OLT) patients, in particular if when there is decreased renal function. We evaluated the efficacy and the causes for discontinuation of sirolimus-based immunosuppression among OLT recipients.Objective. We retrospectively analyzed 97 liver transplanted patients who were prescribed sirolimus as the principal immunosuppressant. Of these, 61 patients discontinued treatment. Herein we have reported the causes, the timing, and the effects of sirolimus discontinuation.Results. The overall patient survival at 3 years follow-up was 89%. Hepatotoxicity and blood disorders were the most frequent, severe reported side effects. Acute cellular rejection episodes appeared in seven patients and was relieved in 1 to 2 weeks after the sirolimus administration. In 10 patients, the cholestasis associated with chronic rejection was sharply reduced after the introduction of sirolimus. No increase in vascular thrombosis and/or poor wound healing were reported.Conclusion. Sirolimus given alone or in combination with CNIs appears to be an effective primary immunosuppressant regimen for OLT patients. However, in the late postoperative period (>3 months) the drug is associated with a relatively high rate of side effects.

M. Audet, T. Piardi, F. Panaro, E. Ghislotti, F. Gheza, M. Cag, T.M. Jarzembowski, H. Flicoteaux, P. Wolf, J. Cinqualbre. Incidence and clinical significance of bacterial and fungal contamination of the preservation solution in liver transplantation. Transpl Infect Dis 2011: 13: 84–88. All rights reserved Abstract: A perfusion fluid used in the preservation of the grafted liver represents a medium suitable for microorganism growth. In this observational study, a sample of 232 transplanted livers was collected. Perfusion fluid samples were stored for microbiological analysis from harvested donors. Bacteria were isolated in 91 out of 232 samples, post‐operative infections related to contaminated perfusion solution occurred in 13 cases. The contamination rate of the preservation medium appears to be high, but postoperative infections occurs rarely. We suggest periodic detection and a protocol in place designed for antibiotic use for transplanted patients exposed to contaminated perfusion solution.

The ability of hepatitis C virus (HCV) to infect leukocytes could favour HCV pathogenesis. Although viral infection of these immunocompetent cells is poorly (or not) productive, the impact on their immunomodulatory functions could be important. Viral envelope glycoproteins E1 and E2, because of their crucial role in the recognition of viral receptors on permissive cells, could contribute to viral leukocytic tropism and, as a consequence, to the pathophysiology of HCV chronic infection. (C) 2009 Elsevier Masson SAS. All rights reserved.

Introduction. The aim of this study was to assess the impact of laparoscopic thermoablation (LTA) as a neoadjuvant therapy prior to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).Methods. Between January 2008 and January 2009, 12 consecutive patients, including 10 males and 2 females with unresectable HCC within liver cirrhosis, were treated with LTA under ultrasound (US) guidance. Most patients were in Child-Pugh class B (54.1%) with a mean age of 60.7 +/- 7.74 years (range, 45-69; median, 60).Results. The LTA procedure was completed in all patients with thermoablation of 23 HCC nodules. LTA identified 4 new malignant lesions (20%) undetected by preoperative imaging (<0.5 cm). The mean length of surgery was 96 minutes (range, 45-118). Six procedures were performed in 4 patients. No postoperative hepatic insufficiency was reported. The mean hospital stay was 4.5 days; no postoperative morbidity was reported. Complete tumor necrosis was achieved in 19/23 thermoablated nodules (82.6%) as evidenced computed tomography (CT) scan by at 3 weeks after the treatment. All patients underwent OLT without complications. The histology of the native liver showed complete necrosis in 17/23 (74%) treated nodules.Discussion. There is currently no convincing evidence that LTA allows one to expand the current selection criteria for OLT, nor that LTA decreases dropout rates on the waiting list. However, LTA does not increase the risk of postoperative complications. There is insufficient evidence that LTA offers any benefit when used prior to OLT either for early or for advanced HCC.

BACKGROUND:Patients undergoing orthotopic liver transplantation (OLT) show a high risk of developing an incisional hernia. The aim of this retrospective study was to establish the incidence and the factors influencing the outcomes of this complication. METHODS:We reviewed 450 consecutive OLT performed in 422 adult recipient between January 2000 and December 2005. Herniae were analysed with aspect to localization, classification, repair technique, and recurrence. All treated herniae were followed for a median of 50.5 months. RESULTS:Incisional herniae occurred in 36 patients (8.5%, Group 1). Their mean age OLT was 51.4 years with 94.4% male subjects. No significant difference was observed between affects and unaffected individuals for age, OLT indication, Child-Pugh score, albumin, comorbidities, operative time, transfusions, immunosuppressant regimen, and graft rejection episodes as well as for the incisional approach and hospital stay. Gender, body mass index (BMI), preoperative ascites, and pulmonary complications after OLT were significantly different (P < .01). Herniae were small (<5 cm; n = 12), medium (5-10 cm; n = 28), or large (> 10 cm; n = 2). Herniorrhaphy techniques included primary suture repair in 5 (13.9%) and mesh repair in 31 (86.1%) cases. In 3 patients with a primary repair and 1 patient with a mesh repair there were recurrences. CONCLUSIONS:Preoperative ascites, gender, BMI, and pulmonary complications after OLT seemed to have significant influences on the formation of incisional herniae. Polypropylene mesh may be a first choice for the surgical treatment of there transplant recipients.

BACKGROUND:In the cardiac death donor era, many reports deal with biliary tract complications and concerns about ischemic reperfusion injury owing to the exclusive arterial vascularization of the biliary tree, the warm ischemia time has been implicated as responsible for biliary lesions during organ procurement. We defined the arterialization time as the second warm ischemia time. Our purpose was to study the correlation between the arterialization time during liver implantation and the appearance of biliary lesions.METHODS:We retrospectively collected data from the last 5-years of orthotopic liver transplantation: namely, indications, cold perfusion fluid, cold ischemia time, operative procedure times, and acute rejection events. We excluded split-liver transplantations, retransplantations, pediatric patients, transplantations for cholestatic disease, cases where hepatic artery thrombosis happened before biliary complications, or patients with posttransplant cytomegalovirus infection. We defined 2 groups: A) without biliary complications; and B) with biliary complications. We compared the mean arterialization time using Student t test to define whether the warm ischemic time during implantation was responsible for biliary tract complications. A P value of <.05 was considered to be significant.RESULTS:Between 2004 and the end of 2008, we grafted 402 patients among whom 243 met the inclusion criteria: 198 in group A and 45 in group B. Only the cold ischemia time was significantly different between the 2 groups (P = .039).CONCLUSION:After the anhepatic time, the surgeon may take time for the arterial anastomosis without fearing increased biliary damage.

L'hépatocarcinome (CHC) est une indication de résection hépatique ou de transplantation hépatique (TH). Dans la plupart des centres, seuls les patients dont le CHC répond aux critères de Milan sont éligibles pour la TH. L'objectif de l'étude est d'analyser la corrélation entre les caractéristiques pathologiques de la tumeur, la survie et le taux de récidive. Dans la période 1997-2007, un diagnostic de CHC a été porté chez 196 patients. Ont été analysés dans cette série l'âge, le sexe, la nature de la cirrhose, les examens biologiques, l'alphafœtoprotéine. Pour tous les patients, les score MELD (Model for End-stage liver disease) et Child-Pugh ont été calculés. S'agissant du CHC, ont été précisés la localisation tumorale, la taille, le nombre de nodules, l'atteinte de la capsule, la différenciation histologique et la présence de micro ou macro-envahissement vasculaires (EV). L'examen histologique a confirmé le diagnostic de CHC chez 168 (85,7 %) patients dont la médiane de survie était de 74 mois (23-154 mois). La mortalité à un mois était de 5,6 %. À l'examen anatomo pathologique des foies explantés, 106 (63 %) patients respectaient les critères de Milan, 28 (16,7 %) ceux de San Fancisco (UCSF), 34 (20,3 %) étaient audelà de ces critères. L'envahissement vasculaires (EV) a été mis en évidence chez 41 patients (24,4 %) : macroscopiques dans 10,7 % des cas (n = 18) et microscopiques dans 13,6 % (n = 23). La survie globale et sans récidive à 5 ans était respectivement de 66,1 % et 64,1 %. Les survies globales à 1, 3 et 5 ans selon les critères de Milan étaient respectivement de 90 %, 85 % et 77 % et selon les critères de UCSF de 88 %, 81 % et 74 % (NS). On a noté une différence de taux de survie entre les patients avec EV et ceux sans EV (p ≤ 0,001). L'analyse univariée et multivariée des facteurs prédictifs de la survie seule l'EV était statistiquement significatif (p < 0,001). Deux facteurs étaient associés à l'EV, l'AFP 400 ng/ml (HR = 13,167, p < 0,002) et la classification histologique G3 (HR = 12,6, p < 0,0003). Dans cette série, le seul facteur pronostique significatif est l'EV. Dans la mesure où on ne dispose pas de marqueurs prédictifs de l'EV fiables, la résection hépatique, lorsque la fonction hépatique le permet, représente non seulement un traitement de première intention, mais une étape décisionnelle avant la TH.

Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. In the present study, we report the long-term follow-up of four end-stage CF patients treated with combined bilateral lung and pancreatic islet transplantation from the same donor. All patients were C-peptide negative (<0.5 μg/L) and inadequately controlled despite intensive insulin treatment. One patient was transplanted with 4 019 ± 490 islet equivalent/kg injected into the transverse colic vein using a surgical approach. In the remaining three patients, islets were cultured for 3–6 days and transplanted by percutaneous transhepatic catheterization of the portal vein. In all patients, islet allograft recovery was recognized by elevation in the plasma level of C-peptide (>0.5 μg/L). At 6 months after transplantation, one patient showed multiple episodes of acute lung transplant rejection and a progressive decline in pancreatic islet cell function. Three out of four patients experienced an improved control of glucose levels with a HbA1c of 5.2%, 7% and 6% respectively at 1.5, 2 and 15 years follow-up. Compared with the pretransplant period, there was a 50% reduction in mean daily insulin needs. Pulmonary function remained satisfactory in all patients. In conclusion, our cases series shows that combined bilateral lung and pancreatic islet transplantation may be a viable therapeutic option for patients with end-stage CF and CFRD.