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Background Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma. Methods Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort. Results Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy. Conclusion Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes.

Background Biliary leakage remains a major cause of morbidity after liver resection. Previous prognostic studies of posthepatectomy biliary leakage (PHBL) lacked power, population homogeneity, and model validation. The present study aimed to develop a risk score for predicting severe PHBL. Methods In this multicentre observational study, patients who underwent liver resection without hepaticojejunostomy in one of nine tertiary centres between 2012 and 2015 were randomly assigned to a development or validation cohort in a 2 : 1 ratio. A model predicting severe PHBL (International Study Group of Liver Surgery grade B/C) was developed and further validated. Results A total of 2218 procedures were included. PHBL of any severity and severe PHBL occurred in 141 (6·4 per cent) and 92 (4·1 per cent) patients respectively. In the development cohort (1475 patients), multivariable analysis identified blood loss of at least 500 ml, liver remnant ischaemia time 45 min or more, anatomical resection including segment VIII, transection along the right aspect of the left intersectional plane, and associating liver partition and portal vein ligation for staged hepatectomy as predictors of severe PHBL. A risk score (ranging from 0 to 5) was built using the development cohort (area under the receiver operating characteristic curve (AUROC) 0·79, 95 per cent c.i. 0·74 to 0·85) and tested successfully in the validation cohort (AUROC 0·70, 0·60 to 0·80). A score of at least 3 predicted an increase in severe PHBL (19·4 versus 2·6 per cent in the development cohort, P < 0·001; 15 versus 3·1 per cent in the validation cohort, P < 0·001). Conclusion The present risk score reliably predicts severe PHBL. It represents a multi-institutionally validated prognostic tool that can be used to identify a subset of patients at high risk of severe PHBL after elective hepatectomy.

RésuméLa résection hépatique par laparoscopie est une technique reconnue comme sûre et efficace depuis la conférence de Louisville en 2008 ; elle reste cependant majoritairement pratiquée par des équipes expérimentées dans des centres spécialisés, et manque encore certainement de standardisation. La session 2013 de l’Association française de chirurgie hépatobiliaire et pancréatique (ACHBT) avait pour thématique la chirurgie laparoscopique et en particulier ses différents aspects et limites depuis 2008. L’objectif de ce document est de résumer cette conférence afin d’obtenir un état des lieux récent de la chirurgie hépatique par laparoscopie et ainsi de présenter la position française sur ce sujet. Ainsi, une vue d’ensemble de la pratique actuelle en chirurgie hépatique laparoscopique depuis 2008 est d’abord présentée. La standardisation de la lobectomie gauche et de l’hépatectomie droite laparoscopiques sont développées. La position française concernant les techniques hybrides et hand-assisted est discutée. Enfin, les perspectives techniques futures et les nouvelles technologies disponibles et en développement sont évoquées.SummaryLaparoscopic liver resection has been recognized as a safe and efficient approach since the Louisville Conference in 2008, but its use still remains confined to experienced teams in specialized centers, and may lack some standardization. The 2013 Session of French Association for Hepatobiliary and Pancreatic Surgery (ACHBT) specifically focused on laparoscopic liver surgery and the particular aspects and issues arising since the 2008 conference. Our objective is to provide an update and summarize the current French position on laparoscopic liver surgery. An overview of the current practice of laparoscopic liver resections in France since 2008 is presented. The issues surrounding standardization for left lateral sectionectomy and right hepatectomy, hybrid and hand-assisted techniques are raised and discussed. Finally, future technologies and technical perspectives are outlined.

BACKGROUND: Liver resection is considered to offer the only hope of cure for patients with liver malignancy. However, there are concerns about its safety, particularly in view of the increasing efficacy of less invasive strategies. No systematic review of prognostic research in liver resections has yet been performed. METHODS: A systematic search identified articles published between 1999 and 2012 that performed a risk prediction analysis in patients undergoing liver resection. Studies were included if an outcome occurring within 90 days of surgery was identified, multivariable analysis performed and regression coefficients provided. The main endpoints were the outcomes and predictors chosen by the investigators, their definition, the performance and validity of the models, and the quality of the study as assessed using the QUIPS (quality in prognosis studies) tool. RESULTS: A total of 91 studies were included. Eleven were prospective, but only two of these were registered. Twenty-eight endpoints were identified. These focused on postoperative morbidity or mortality, but many were redundant or ill defined and other relevant patient-reported outcomes were lacking. Predictors were not standardized, were poorly defined and overlapped. Only nine studies assessed the performance of their models and seven made an internal or temporal validation, but none reported an external validation or impact analysis. The median QUIPS score was 34 out of 50, indicating a high risk for bias. CONCLUSIONS: Prognostic research in liver resection is still at the developmental stage.

Background The operative risk of hepatectomy under antiplatelet therapy is unknown. This study sought to assess the outcomes of elective hepatectomy performed with or without aspirin continuation in a well balanced matched cohort. Methods Data were retrieved from a multicentre prospective observational study. Aspirin and control groups were compared by non-standardized methods and by propensity score (PS) matching analysis. The main outcome was severe (Dindo–Clavien grade IIIa or more) haemorrhage. Other outcomes analysed were intraoperative transfusion, overall haemorrhage, major morbidity, comprehensive complication index (CCI) score, thromboembolic complications, ischaemic complications and mortality. Results Before matching, there were 118 patients in the aspirin group and 1685 in the control group. ASA fitness grade, cardiovascular disease, previous history of angina pectoris, angioplasty, diabetes, use of vitamin K antagonists, cirrhosis and type of hepatectomy were significantly different between the groups. After PS matching, 108 patients were included in each group. There were no statistically significant differences between the aspirin and control groups in severe haemorrhage (6·5 versus 5·6 per cent respectively; odds ratio (OR) 1·18, 95 per cent c.i. 0·38 to 3·62), intraoperative transfusion (23·4 versus 23·7 per cent; OR 0·98, 0·51 to 1·87), overall haemorrhage (10·2 versus 12·0 per cent; OR 0·83, 0·35 to 1·94), CCI score (24 versus 28; P = 0·520), major complications (23·1 versus 13·9 per cent; OR 1·82, 0·92 to 3·79) and 90-day mortality (5·6 versus 4·6 per cent; OR 1·21, 0·36 to 4·09). Conclusion This observational study suggested that aspirin continuation is not associated with a higher rate of bleeding-related complications after elective hepatic surgery.

Background The impact of morbidity on long-term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear. Methods This was a retrospective analysis of all consecutive patients who underwent liver resection for intrahepatic cholangiocarcinoma with curative intent in 24 university hospitals between 1989 and 2009. Severe morbidity was defined as any complication of Dindo–Clavien grade III or IV. Patients with severe morbidity were compared with those without in terms of demographics, pathology, management, morbidity, overall survival, disease-free survival and time to recurrence. Independent predictors of severe morbidity were identified by multivariable analysis. Results A total of 522 patients were enrolled. Severe morbidity occurred in 113 patients (21·6 per cent) and was an independent predictor of overall survival (hazard ratio 1·64, 95 per cent c.i. 1·21 to 2·23), as were age at resection, multifocal disease, positive lymph node status and R0 resection margin. Severe morbidity did not emerge as an independent predictor of disease-free survival. Independent predictors of time to recurrence included severe morbidity, tumour size, multifocal disease, vascular invasion and R0 resection margin. Major hepatectomy and intraoperative transfusion were independent predictors of severe morbidity. Conclusion Severe morbidity adversely affects overall survival following liver resection for intrahepatic cholangiocarcinoma.

Resume Introduction La decouverte d’un cancer vesiculaire sur piece de cholecystectomie est frequente. En raison du risque important de greffe tumorale sur les orifices de trocarts, il est recommande de les resequer au cours de la re-intervention. L’objectif de cette etude etait d’evaluer l’interet de l’exerese des orifices de trocarts au cours d’une re-intervention. Methodes Les patients ayant un cancer vesiculaire sur piece de cholecystectomie pris en charge entre 1998 et 2008 etaient retrospectivement collectes dans une base de donnees nationale multicentrique. Les patients ayant eu une l’exerese des orifices de trocarts etaient compares aux patients reseques sans exerese des orifices de trocarts. Les donnees demographiques, histologiques et de survie etaient analysees. Resultats Parmi les 218 patients ayant un cancer vesiculaire sur piece de cholecystectomie, il y avait 68 hommes et 150 femmes (âge median : 64 ans [46–86]). Parmi les 148 patients ayant une re-intervention a visee curative, 54 (36 %) ont eu une exerese des orifices de trocarts alors que les 94 autres patients n’ont pas eu d’exerese des orifices de trocarts. Les deux groupes etaient comparables en termes de donnees demographiques (sexe masculin 28 vs. 35 %, p = 0,33, âge > 70 ans 22 vs. 22 %, p = 0,50 et co-morbidites), procedures chirurgicales (curage ganglionnaire 87 vs. 86 %, p = 0,07, resection de la voie biliaire principale 37 vs. 46 %, p = 0,35) et postoperatoire (morbidite 30 vs. 41 %, p = 0,29). Dans le groupe avec exerese des orifices de trocarts, le stade tumoral etait T1b (n = 3), T2 (n = 25), T3 (n = 26), comparable au groupe sans exerese des orifices de trocarts (p = 0,97). L’envahissement histologique de l’exerese des orifices de trocarts etait observe chez un patient (2 %) ayant une tumeur T3, qui est decede 15 mois apres la re-resection d’une carcinose peritoneale. L’exerese des orifices de trocarts n’ameliorait pas la survie globale (77 %, 58 %, 21 % a un, trois, cinq ans, respectivement), comparativement aux patients sans exerese des orifices de trocarts (78 %, 55 %, 33 % a un, trois et cinq ans, respectivement, p = 0,37). Huit pour cent des patients avec exerese des orifices de trocarts ont developpe une eventration. Conclusion Chez les patients avec un cancer vesiculaire sur piece de cholecystectomie, l’exerese des orifices de trocarts n’ameliorait pas la survie globale et ne devrait pas etre consideree comme systematique au cours de la re-intervention a visee curative.

Resume Le seul traitement curatif des metastases hepatiques d’origine colorectale (MHCCR) est la chirurgie, sous reserve de resequer la totalite des lesions avec une marge saine et en laissant un volume de parenchyme residuel suffisant. Le rationnel de l’embolisation portale (EP) pour reduire le risque de ces hepatectomies est triple : premierement, la chirurgie des MHCCR est de plus en plus extensive et l’insuffisance hepatocellulaire represente la premiere cause de mortalite apres hepatectomie majeure pour metastases hepatiques (MH) ; deuxiemement, l’existence d’une hepatopathie sous-jacente, plus frequente que l’on ne le pensait chez ces patients du fait des chimiotherapies neoadjuvantes et du terrain, pourrait alterer la fonction hepatique ou les capacites de regeneration postoperatoires et, troisiemement, le risque operatoire pourrait etre majore si une hepatectomie majeure est associee a un geste d’exerese de la tumeur primitive. L’objectif de cette mise au point est, dans ce contexte specifique des MHCCR, de detailler la justification et les indications de l’EP, d’analyser les donnees de la litterature permettant de determiner si son indication doit etre systematique ou selective et d’aborder certains aspects techniques qui lui sont propres.

Resume La creation du pneumoperitoine etant la source d’environ 50 % des complications des laparoscopies, l’etablissement d’une check-list technique complementaire, specifique a la laparoscopie, semble etre justifie. Un dysfonctionnement ou une mauvaise utilisation du materiel technique peut etre source d’evenements indesirables lors des procedures cœlioscopiques. Par ailleurs, la creation du pneumoperitoine necessite la mise en place de barrieres et le reperage des situations a risque. A partir de la base de donnees REX et d’une revue exhaustive de la litterature, nous avons identifie les barrieres a mettre en place pour prevenir les risques lies a l’etablissement du pneumoperitoine lors des cœlioscopies, ainsi qu’une check-list preoperatoire. Nous proposons une check-list concernant « l’aspect environnemental et technique » de la procedure laparoscopique. Celle-ci permettrait de reduire les incidents mineurs qui sont potentiellement la source des incidents majeurs. L’aspect technique de la check-list permet de reperer a chaque etape de la creation du pneumoperitoine les situations a risque pour la technique par voie ouverte ou fermee ; ainsi que la conduite a tenir en cas d’echec a chacune de ces etapes.

Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions.

Resume Dans ce chapitre est rapporte le compte rendu du symposium Nycomed intitule « 60 minutes pour comprendre : de l’hemostase aux regles du management »

Laparoscopic distal pancreatectomy is currently a commonly performed procedure. Twenty-five retrospective studies comparing laparotomy and laparoscopy have dealt with the feasibility of this approach for localized benign and malignant tumors. However, these studies report several different techniques. The aim of this review was to determine if a standardized procedure could be proposed. Based on the literature and the experience of surgeons in the French Association of Hepatobiliary Surgery and Liver Transplantation (ACBHT-Association française de chirurgie hépato-biliaire et de transplantation hépatique), we recommend primary control of the splenic artery, use of linear staplers for pancreatic transection, splenic vein control either at its end or its origin, and, depending on local conditions, preservation of the splenic vessels when splenic preservation is envisioned. Current data do not allow establishment of any definitive recommendations as to the ideal site of pancreatic transection, operative patient position, or the direction of dissection, which mainly depends on local practices. Control of the splenic vein remains the critical point of this procedure, and impacts the intra-operative strategy.

SummaryLaparoscopic liver resection has been recognized as a safe and efficient approach since the Louisville Conference in 2008, but its use still remains confined to experienced teams in specialized centers, and may lack some standardization. The 2013 Session of French Association for Hepatobiliary and Pancreatic Surgery (ACHBT) specifically focused on laparoscopic liver surgery and the particular aspects and issues arising since the 2008 conference. Our objective is to provide an update and summarize the current French position on laparoscopic liver surgery. An overview of the current practice of laparoscopic liver resections in France since 2008 is presented. The issues surrounding standardization for left lateral sectionectomy and right hepatectomy, hybrid and hand-assisted techniques are raised and discussed. Finally, future technologies and technical perspectives are outlined.

Resume L’insuffisance hepatocellulaire est une complication grave des hepatectomies larges, en particulier lorsqu’il existe une hepatopathie sous jacente. L’interruption prealable de la vascularisation portale des territoires que l’on souhaite resequer, permet d’induire leur atrophie et, par hypertrophie compensatrice, d’augmenter le volume du parenchyme qui persistera au terme de cette exerese. Cette obstruction peut etre provoquee par une ligature chirurgicale ou par l’injection percutanee sous controle echographique de colles ou de substances sclerosantes. Une embolisation portale est habituellement indiquee lorsque le volume residuel previsible represente moins de 25 a 40 % du volume hepatique total. L’embolisation percutanee a une faisabilite proche de 100 % et son risque est comparable a celui d’une biopsie percutanee. Elle est cliniquement tres bien toleree et les consequences biologiques sont minimes chez les patients n’ayant pas d’insuffisance hepatocellulaire. L’hypertrophie est maximale au cours des 15 premiers jours puis se ralentit mais persiste pendant environ six semaines. Son intensite est proportionnelle au volume de parenchyme embolise ; elle est diminuee lorsqu’il existe un diabete, un ictere ou une hepatopathie chronique active sous jacente. L’hepatectomie est realisee deux a six semaines apres l’embolisation. Les etudes retrospectives et une etude prospective suggerent que les patients ainsi prepares ont un risque operatoire diminue et que leur pronostic carcinologique est comparable a celui de patients d’emblee operables.

Background. Recurrence of primary biliary cirrhosis (PBC) within liver allografts remains a controversial issue. The aims of this study were to evaluate this risk and to determine the presence, if any, of a predictive histological feature. Methods. We reviewed the most recent and the 1-year protocol liver biopsies of 69 patients who received transplants for PBC and of 53 control patients. Histological features consistent with PBC recurrence included nonsuppurative destructive cholangitis, mixed portal infiltrate, fibrosis, and ductopenia. A complete evaluation was undertaken in each patient with these histological features. Results. These histological features were present in six patients who received transplants for PBC (8.7% vs. 0% in the control group) and occurred between 1 and 8 years after transplant. In five of the six patients, anti-mitochondrial antibody-2 (anti-M2) antibodies remained at high titers. Cholestasis was present in four patients, and clinical symptoms in two patients. All six patients were negative for hepatitis C antibodies and hepatitis C RNA in their serum. None had bile duct obstruction. The presence of plasma cells in the portal infiltrate at 1 year after transplant was predictive of this risk of recurrence. Conclusion. The risk of PBC recurrence is real (8.7%). The presence of plasma cells in the portal infiltrate seems to be an early marker of recurrence of PBC in patients transplanted for this indication.

Background. The precise immunologic mechanisms responsible for chronic rejection of liver allografts are unknown. We have recently shown in a rodent model that recipients of liver allografts developed non-major histocompatibility complex antitissue antibodies. The aim of the present study was to test this hypothesis in the clinical setting. Methods. Posttransplant sera of 14 patients undergoing chronic rejection and of 48 control patients (12 liver transplant patients with chronic active hepatitis or liver cirrhosis related to hepatitis C virus [HCV] infection and without chronic rejection, 10 with sclerosing cholangitis, and 26 with normal liver function tests and liver biopsy) were tested for the presence of antitissue antibodies by indirect immunofluorescence. Pretransplant sera of all these patients lacked antitissue antibodies. Results. Antitissue antibodies were detected in 71% of patients who developed chronic rejection (before or at the time of chronic rejection). This incidence was significantly greater than that observed in patients not undergoing rejection (HCV-related chronic active hepatitis, 16%; sclerosing cholangitis, 0%; normal liver biopsy, 7%). All these autoantibodies were directed against the smooth muscle and/or the nucleus. In two patients, anti-smooth muscle antibodies had an antiactin or antivimentin specificity. Conclusions. These results show a strong association between chronic allograft rejection and the development of antitissue antibodies and suggest that these antibodies could be used to identify patients at high risk of developing chronic rejection after liver transplantation.

A retrospective analysis was undertaken to determine if the incidence, timing, and severity of acute and chronic rejection were influenced by the primary disease necessitating transplantation. Of the 875 liver transplantations performed between 1984 and 1992, 768 were primary transplantations and 107 were retransplantations. Among the former, 330 patients that were liver transplant recipients for a chronic liver disease without cancer in the native liver received an ABO-compatible and cross-match-negative graft and were given a cyclosporine- or tacrolimus-based immunosuppression. These included primary biliary cirrhosis (PBC, 66 patients), primary sclerosing cholangitis (PSC, 23 patients), alcoholic cirrhosis (ALC, 21 patients), autoimmune cirrhosis (AIC, 17 patients), hepatitis B virus-induced cirrhosis (HBV-C, 116 patients) and hepatitis C virus-induced cirrhosis (HCV-C, 87 patients). The incidence of acute (48% +/- 3% [SE] at 1 year) and chronic rejection (10% +/- 2% at 3 years) was comparable in patients who have undergone transplantation for PBC, PSC, AIC, and HCV-C. However, the incidence of acute (but not chronic) rejection was significantly lower in patients who have undergone transplantation for ALC (29% at 1 year). This reduced incidence of acute rejection was associated with an increased incidence of bacterial infections. In patients who have undergone transplantation for HBV-C (the majority of whom had received long-term anti-hepatitis B surface antigen [HBs] immunoglobulins), the incidence of both acute (21% at 1 year) and chronic rejection (0% at 3 years) was significantly lower, whereas the incidence of septic complications was comparable with that in the other groups. The incidence of acute rejection in patients who have undergone transplantation for nonviral disease receiving polyclonal human anti-cytomegalovirus (CMV) immunoglobulins was also significantly lower than that of patients who did not receive the immunoglobulins (19% vs. 48% at 3 months; P = .01), and this was identical to that of patients who have undergone transplantation for viral disease receiving polyclonal human anti-HBs immunoglobulins (19% at 3 months). These results show that the risk of rejection is unequal among patients, being lower in patients who have undergone transplantation for ALC (probably as a result of a state of nonspecific hyporesponsiveness) and in patients who have undergone transplantation for HBV-C (possibly as a result of long-term administration of polyclonal human immunoglobulins).

Background/Aims: Orthotopic liver transplantation is currently considered as the treatment of choice for primary biliary cirrhosis in the terminal stage and, as for other autoimmune liver disease, the risk of recurrence of the disease within the graft has been raised. There is, however, some discrepancy about the risk of recurrence based on pathological analysis. In addition, pathological recurrence of primary biliary cirrhosis within the graft is not always associated with a rise in the serological markers of the disease. In order to clarify this situation, we have monitored antimitochondrial antibodies before and after transplantation. Methods: Antimitochondrial antibodies were detected by indirect immunofluorescence (variation in antibody titers) and the antimitochondrial antibodies-2 by western blotting (variation in the number of peptides recognized) in 16 primary biliary cirrhosis patients followed for at least 4 years after transplantation. Results: Antimitochondrial antibody titers had normalized 1 year after transplantation in seven patients, declined in seven others and remained unchanged in two. Over the 4 years of follow up, four patients demonstrated a subsequent increase in antimitochondrial antibody titers. Western blot analysis demonstrated the loss of one or more bands in seven patients during the first operative year after transplantation and in three other patients thereafter; in six patients the western blotting profile remained identical to that obtained before transplantation. The important changes generally occurred during the first year post-transplantation, without significant changes thereafter, except for three patients who demonstrated a secondary reappearance of the initially lost band. Disappearance of all bands was never observed. There was no concordance between the normalization of antimitochondrial antibody titers (indirect immunofluorescence) and the reduction in the number of peptides recognized (western blotting). Serum bilirubin and alkaline phosphatase levels had normalized by 1 year after transplantation, and remained normal thereafter. Routing liver biopsies performed on a yearly basis did not disclose any pattern suggestive of primary biliary cirrhosis recurrence. Conclusions: Antimitochondrial antibody titers decreased in primary biliary cirrhosis patients after liver transplantation, although antimitochondrial antibodies-2 never disappeared as assessed by western blotting. In the present study these features were not associated with biochemical or histoclogical evidence of primary biliary cirrhosis recurrence.

Alphafetoprotein (AFP), a major serum protein synthesized during the embryo-fetal and postnatal period (in the yolk sac, then in the liver), is also an oncoprotein. The intracellular presence of AFP and of serum albumin (SA) in normal and neoplastic neural crest and neural tube derivatives was previously demonstrated. In this work we have studied the comparative expression of AFP and SA in primitive neuroectoblastic structures of mouse embryos (6 and 7 days post coitum) and mouse teratocarcinomas (derived from the PCC4 cell line). Using immunofluorescence technique, antibodies to SA gave a positive reaction in embryos of 7 days, while AFP was not detected during this period. By mRNA in situ hybridization, SA mRNA gave a strong signal in both 6 and 7 day embryos, whereas AFP mRNA gave a weak signal only in 7-day embryos. The distribution of SA and AFP and their mRNAs was investigated in primitive neuroectoblastic structures of the teratocarcinomas by in situ hybridization and immunostaining. Only SA protein was detectable by immunostaining. SA mRNA gave a strong signal in differentiating structures as well as in undifferentiated cell clusters. AFP mRNA was observed only in differentiating structures. Dot-blot hybridization indicated that the level of SA transcripts was at least 6-fold higher than that of AFP transcripts in the teratocarcinomas investigated. In teratocarcinoma-bearing mice injected intraperitoneally with 125 I-radiolabeled SA and AFP, significant accumulations of both SA and AFP were demonstrated in the tumors, SA being about 3-fold higher than that of AFP after normalization to quantity of uptake in liver. External in vivo photoscanning confirmed this relationship of accumulated radiolabeled proteins. The last observation could be useful in vivo for diagnosis of teratocarcinoma. We conclude that the expression of SA relative to AFP and the external cellular uptake of SA relative to AFP are similar in normal embryonic developing tissues and in the corresponding morphologically neoplastic tissues of the teratocarcinomas. The same SA:AFP relationship constitutes an oncofetal marker of primitive neuroectoblastic structures.

Liver allografts are not rejected in the fully incompatible Lewis-RT1 1 (LEW) to blood group D Agouti-RT1 a (DA) rat strain combination despite an early infiltration by recipient mononucleated cells that initially display a phenotype, an ability to respond to interleukin-2 (IL-2) and donor-specific cytotoxicity indistinguishable from that observed in the rejected, DA to LEW combination. To further analyze the mechanism of this tolerance, we have compared in these two combinations, as well as in syngeneic grafts and in normal livers, the presence of intrahepatic cytokine transcripts (IL-1α, IL−2, IL−4, IL−6, IL−10, tumor necrosis factor [Tnf]-α, TNF-β, and transforming growth factor [Tgf]-β) by a semiquantitative polymerase chain reaction (PCR) or by northern-blotting. In normal livers or syngeneic grafts, IL-1α, TNF-β, and TGF-β were the only cytokines detected by these methods. The levels of all cytokine transcripts were increased in allogeneic grafts. Expression of cytokine transcripts was very similar in the two allogeneic strain combinations except IL−4, which was expressed at a much lower level in the nonrejected strain than in the rejected strain from day 2 onward. We conclude that selective downregulation of IL−4 gene expression is associated with, and a potential mediator of, the induction of tolerance in this model.

A multicenter randomized trial was performed to compare two immunosuppressive protocols after first ABO-compatible liver transplantation. Forty six patients were randomized to a 14-day treatment with Orthoclone (OKT3) in association with steroids and azathioprine, cyclosporine being progressively introduced on day 11 posttransplant. Fifty patients were randomized to a standard protocol of cyclosporine with steroids and azathioprine. Minimum follow-up was 1 year and graft and patient survivals were updated for the purpose of the study. The cumulative 1-year incidence of acute rejection tended to be greater in the cyclosporine group (75%) than in the OKT3 group (67%), especially when patients who did not receive full-course treatment with OKT3 were excluded (59%). Renal function was better preserved during the first two postoperative weeks in the OKT3 group than in the control group but plasma creatinine levels were comparable in both groups thereafter. The incidence of severe infections was lower in the OKT3 group (13.6%) than in the cyclosporine group (32%). The 4-year incidences of patient and graft survival in the OKT3 group (69% and 61%, respectively) were not different from those in the cyclosporine group (62% versus 54%, respectively). Thus this prospective trial shows that OKT3 immunoprophylaxis is a safe alternative to cyclosporine immunoprophylaxis in unselected recipients of a first liver graft.

In a model of arterialized rat liver transplantation, the biological indicators of liver dysfunction and the phenotype and in vitro function of graft-infiltrating cells have been compared in rejected (DA-to-Lew) and spontaneously accepted (Lew-to-DA) grafts, 2-8 days after grafting. Recipients of rejected and nonrejected allografts had, during this time, similar loss in body weight and plasma levels of transaminase. The markers of cholestasis, however, increased from days 3 and 4 onward in the recipients of rejected grafts, but remained low and similar in the recipients of nonrejected allografts and those of syngeneic grafts. From days 2 to 6 the phenotype, IL-2 responsiveness, and donor-specific cytotoxic potential of the leukocytes infiltrating rejected and nonrejected allografts were comparable. On days 7 and 8, although the proportion of T cell subpopulations was identical in both combinations, activated CD4+ graft-infiltrating cells were reduced in the nonrejected grafts. Also at this time, donor-specific cytotoxic cells were no longer detected in nonrejected grafts, whereas activity had reached a peak in the rejected grafts. These results suggest that liver grafts in both the LEW-->DA (grafts not rejected) and DA-->LEW (grafts rejected) strain combinations undergo tissue damage, but that the type of damage differs between the two combinations. Specifically, cholestasis was only observed in grafts that would subsequently be rejected. The difference in graft damage occurred at a very early time point (3 or 4 days after grafting), at which time neither the intensity nor phenotype of the graft infiltrate, its IL-2 responsiveness, or its cytotoxic potential varied between the two combinations. Thus, a lack of immune reactivity, as assessed by these parameters, does appear not to be responsible for spontaneous acceptance of liver transplants in the LEW-->DA strain combination.

Purpose: The aim of the authors was to report their experience with living related liver transplantation (LRLT) in children, particularly focusing on the safety of the two-center "Parisian' strategy. Methods: The records of donors and recipients of 26 pediatric living-related donor liver transplantations performed between November 1994 and March 1998 were reviewed retrospectively. Donors were assessed 1 year after transplantation for medical and overall status. Results: Indications for LRLT included biliary atresia (n = 18), Byler's disease (n = 5), alpha-1-antitrypsin deficiency (n = 1), Alagille syndrome (n = 1), and undefined cirrhosis (n = 1). Liver harvesting consisted of either a complete left hepatectomy (n = 14) or left lateral hepatectomy (n = 12) without vascular clamping. The recipient procedure essentially was the same as in split liver transplantation. Mean overall cold ischemia time averaged 140 minutes (range, 90 to 230 minutes). Twenty-four of 26 patients had end-to-end vascular anastomoses without interposition. Biliary reconstruction consisted of a Roux-en-Y choledochojejunostomy in all patients. All recipients except one received cyclosporine A (CSA). Mean donor hospitalization was 8 days (range, 6 to 13) with normalization of all liver function assays by the time of discharge. There were no donor deaths and two postoperative complications (perihepatic fluid collection and bleeding from the wound). One year after donation, the initial 19 donors had resumed their pretransplant status. Two of the children who underwent transplant died. Thirteen of the recipients required reoperation for hepatic artery thrombosis (n = 2), portal vein thrombosis (n = 2), biliary complications (n = 6), fluid collection (n = 3), small bowel perforation (n = 1), and plication for diaphragmatic eventration (n = 1). With mean follow-up of 2 years, 24 of 26 patients are alive and well (patients and graft survival rate, 92%). Conclusions: LRLY is still controversial, even with minimal and decreasing donor risk. The "Parisian" strategy consists of harvesting the liver in an adult unit by an adult hepatic surgery team. The transplantation is then performed in a pediatric hospital by the pediatric liver transplantation team. The two steps of the procedure allow units specialized in adult surgery, on one hand, and pediatric liver transplantation, on the other hand, to dedicate themselves completely to their respective procedures, improving the safety of the harvest, and alleviating stress for both the medical staff and the families.

Cholangiocarcinoma, or biliary tract tumors, are rare tumors for which survival is short, as diagnosis is often made at an advanced stage. Indeed, diagnosis remains difficult, since symptoms are often unspecific and appear at latest stages. This article presents an update of recent data and therapeutic options.Several etiologic factors have been identified, but for most patients, none of these factors can be found. Prognosis is often poor, and remains difficult to establish because of the lack of sufficient large-scale studies looking at the impact on preexisting tumor characteristics on overall survival. Surgery remains when possible the gold standard. When tumor removal is impossible, due to a local extension, the appropriate care of patients remains to be defined. Chemotherapy has been proposed with evidence of objective response but limited data on its ability to prolong overall survival and to enhance quality of life. Active chemotherapies appear to be made from combination of an antimetabolite, such as 5-fluorouracile or gemcitabine, and a platinum drug.In the near future, indications of chemotherapy could be enlarged and targeted therapy might also be used, since several molecules have been tested in preclinical studies, and be offered to patients in clinical trials.

Introduction Depression is one of the main causes of disability in the Western countries. This evidence presents new challenges for somatic medicine, such as surgery. Objectives To determine the influence of patients’ depression on (i) length of hospital stay (LOS, which is a proxy of recovery) after major surgery, and (ii) LOS anticipated by surgeon preoperatively. Aims To explore the influence of depression on recovery after major surgery, and whether and how surgeons take into account patients’ emotional and psychological status in the care of their patients. Methods Prospective multicentre observational study. Depression was assessed with HADS (HADS > 8 showing the presence of significant depression). Two cox PH models were fitted to evaluate the influence of depression on patients’ LOS (first model) and anticipated LOS (second model). Adjustment variables were (i) preoperative (age, sex, anxiety, diagnosis, BMI, biology), (ii) intraoperative (blood transfusion, length of intervention), (iii) postoperative (morbidity). Results Of 372 recruited patients (which had undergone major liver surgery), 69 (18,5%) had HADS>8. After adjustment, depression was a risk factor for a prolonged LOS (HR 1.96, 95%CI 1.44–2.63). However, depression was unrelated to the anticipated LOS (HR 1.26, 95%CI 0.90–1.66). Conclusions 1 in 5 patients presented a significant level of depression. Depression was independently associated to longer LOS (ie. longer recovery time after surgery). However this data was not taken into account by surgeons, which failed to integrate that in their previsions. A psychiatric culture and education need to be developed in surgery, as well as more collaboration.

Background. The aim of this study was to analyze the humoral immune response associated with orthotopic liver transplantation in the rat liver transplant model, and in particular to test the presence of anti-tissue antibodies. Methods. Rearterialized liver transplantations were performed in the Dark Agouti (DA)-to-Lewis (LEW) and the LEW-to-DA rat strain combinations. Sera of recipients were analyzed by immunofluorescence (on DA and LEW organ sections) and by western blotting (with DA and LEW liver proteins). Results. We have shown that liver (but not heart or skin) recipients develop a humoral response against non-MHC tissue antigens as evidenced (1) by a pattern of staining comparable to that described in human patients harboring anti-smooth muscle antibodies and (2) by the presence of donor liver peptides recognized in the sera of the recipient by Western blotting. bi]Conclusions. These experiments indicate that orthotopic transplantation of a nonacutely rejected liver allograft is associated with the development of a previously undescribed anti-tissue antibody response that seems to be neither organ nor MHC restricted.

BACKGROUND/AIMS: Postoperative increase of serum transaminase levels is accepted as the most accurate marker of hepatocyte injury after hepatectomy. Vascular clamping is considered as the main factor of liver injury. However, several studies failed to establish a correlation between the postoperative serum transaminase levels and the type and duration of vascular clamping. Therefore, we prospectively evaluated sequential changes of serum transaminase levels during and after liver resection. METHODS: Between June 2003 and September 2003, 40 patients, aged 53±14 years, who underwent elective, exclusive hepatic resection on normal liver, were included in a prospective study. Major resection (>3 segments) was present in 33 (82%). Liver transection was performed in 20 patients under intermittent clamping for a mean duration of 37 min (range 15–64 min); the other 20 cases had no vascular occlusion. All patients underwent serial blood samples assessing transaminase levels (ALT) during surgical procedure, respectively before incision, before liver transection and before abdominal closure and postoperatively, respectively on days 1, 2, 5 and 7. RESULTS: The overall intraoperative measurement of ALT was respectively 31±11 before incision; 134±62 before transection and 222±117 before abdominal closure. ALT serum levels before abdominal closure were not statistically different between the two groups with and without clamping (212±101 vs 233±133). Postoperative ALT serum levels were similar between the two groups, with and without clamping, on days 1, 2, 5 and 7; respectively 289±99 vs 341±246; 227±111 vs 314±254; 127±62 vs 157±130; 73±43 vs 109±91. CONCLUSIONS: Our results show that, during liver resection, serum transaminase levels start to increase early, before the parenchymal transection and that the peak on day 1 was not related to the presence of clamping. These results suggest that other factors of hepatocyte injury, such as manipulation or compression of the parenchyma, should be taken in account.

Acute pancreatitis can complicate non-selective transcatheter arterial embolization of hepatocellular carcinoma with an incidence ranging from 1,7% (acute clinical pancreatitis) to 40% (biological pancreatitis). This complication is thought to be related to embolization of extrahepatic arterial collaterals. We report herein a case of acute clinical pancreatitis developing within 24 hours after a second course of selective transcatheter arterial chemo-embolization into the proper hepatic artery. Neither anatomical arterial variation nor particular risk factor for acute pancreatitis could be identified. This complication is unusual after selective arterial embolization. Because it may clinically mimick a postembolization syndrome, dosage of serum pancreatic enzymes should be performed systematically in case of abdominal pain following chemoembolization.

Surgical liver resection has been demonstrated in Asian countries to be the best therapeutic option in patients with hepatocellular carcinoma. Because the value of this treatment is still debated in Western countries, the aim of this paper was to report a European experience of resection for hepatocellular carcinoma.From 1990 to 1999, 239 men and 61 women aged from 15 to 77 years old underwent 328 resections including major resection in 138 (42%) cases. Normal liver was present in 53 patients (17%) and chronic liver disease was present in 247 including 152 (50%) with cirrhosis.In-hospital mortality was 6.4% and was significantly influenced by the presence of chronic liver disease (1.7% vs. 7.4%). Mortality after resection in alcoholic patients (14%), in patients with hepatitis C (9%) was significantly higher than in patients chronic hepatitis B (1%) (P0.05). The overall survival rates were 81%, 57%, 37%, and 13% at 1, 3, 5 and 10 years. Five-year survival rate was significantly higher (P0.05) in patients with normal liver as compared to chronic liver disease (50% vs. 34%). In patients with chronic liver disease parameters, which significantly influenced survival rate, were vascular invasion, tumor differentiation and the extent of resection.In this European study with varied profile of etiologies associated with hepatocellular carcinoma we showed that a five-year survival rate of 40% can be expected after resection and that chronic liver disease is a major factor influencing short and long-term prognosis.