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Background Transjugular intrahepatic portasystemic stent shunt (TIPSS), instead of surgical shunt, has become the standard treatment for patients with complicated portal hypertension. This study compared outcomes in patients who underwent TIPSS or surgical shunting for complicated portal hypertension. Methods This was a retrospective study of all consecutive patients who received portasystemic shunts from 1994 to 2014 at a single institution. Patients who underwent surgical shunting were compared with those who had a TIPSS procedure following one-to-one propensity score matching. The primary study endpoints were overall survival and shunt failure, defined as major variceal rebleeding, relapse of refractory ascites, irreversible shunt occlusion, liver failure requiring liver transplantation, or death. Results A total of 471 patients received either a surgical shunt or TIPSS. Of these, 334 consecutive patients with cirrhosis who underwent elective surgical shunting (34) or TIPSS (300) for repeated variceal bleeding or refractory ascites were evaluated. Propensity score matching yielded 31 pairs of patients. There were no between-group differences in morbidity and 30-day mortality rates. However, shunt failure was less frequent after surgical shunting than TIPSS (6 of 31 versus 16 of 31; P = 0·016). The 5-year shunt failure-free survival (77 versus 15 per cent; P = 0·008) and overall survival (93 versus 42 per cent; P = 0·037) rates were higher for patients with surgical shunts. Multivariable analysis revealed that a Model for End-Stage Liver Disease (MELD) score exceeding14 and TIPSS were independently associated with shunt failure. In patients with MELD scores of 14 or less, the 5-year overall survival rate remained higher after surgical shunting than TIPSS (100 versus 40 per cent; P < 0·001). Conclusion Surgical shunting achieved better results than TIPSS in patients with complicated portal hypertension and low MELD scores.

Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, 'progression' of AFP was defined by >15 microg/L per month before LT. A total of 127 (83%) were transplanted under and 26 (16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP>15 microg/L per month and preoperative nodules>3 were associated with decreased OS. Progression group and age>60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor>30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP>15 microg/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness.

Background Although recent advances in surgery and chemotherapy have increasingly enabled hepatectomy in patients with initially unresectable colorectal liver metastases (CRLM), not all such patients benefit from surgery. The aim of this study was to develop a nomogram to predict survival after hepatectomy for initially unresectable CRLM. Methods Patients with initially unresectable CRLM treated with chemotherapy followed by hepatectomy between 1990 and 2012 were included in the study. A nomogram to predict survival was developed based on a multivariable Cox model. The predictive performance of the model was assessed according to the C-statistic, Kaplan–Meier curve and calibration plots. Results Of a total of 439 patients, liver and globally completed surgery was achieved in 380 (86·6 per cent) and 335 (76·3 per cent) patients respectively. The 5-year overall and disease-free survival rates were 39·9 and 10·0 per cent respectively. Based on the Cox model, the following five factors were selected for the nomogram and assigned specific scores: node-positive primary, 5; more than six metastases at hepatectomy, 7; carbohydrate antigen 19–9 level at hepatectomy above 37 units/ml, 10; disease progression during first-line chemotherapy, 9; and presence of extrahepatic disease, 4. The model achieved relatively good discrimination and calibration, with a C-statistic of 0·66. The overall survival rate for patients with a score greater than 16 was significantly worse than that for patients with a score of 16 or less (5-year survival rate 4 versus 46·3 per cent respectively; P < 0·001). Conclusion The nomogram facilitates personalized assessment of prognosis for patients with initially unresectable CRLM treated with chemotherapy and with planned resection.

Because of the worse results from retransplantation in relation to the initial liver transplantation, there is a need to refine the indication for retransplantation, such that fair distribution of this benefit is obtained.This was a study of 139 patients who underwent liver retransplantation. Thirty variables were studied: 18 relating to the recipient and 12 to the donor. All the independent variables were initially compared with the length of survival using univariate analyses. Variables presenting significance were compared with the dependent variable of length of survival, to determine which factors were related to longer survival among patients, when evaluated together.A multivariate model for determining long-term survival among patients with retransplants was built up using the following variables: recipient's age, creatinine, urgency of retransplantation and early failure of the first graft. Through this multivariate model it was possible to determine a score that was categorized according to tertile distributions (below the 33rd percentile, score24; 33rd to 66th percentile, 24or = scoreor = 32; above the 66th percentile, score32). One-year, 3-year, and 5-year patient survival rates following retransplantation were respectively 85%, 82%, and 77% for scores24; 69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores32 (P0.0001).The variables of recipient's age, creatinine, urgency of retransplantation, and early failure of the initial transplantation were factors that were independently related to the long-term survival of patients with liver retransplants.

This phase I-II trial was designed to assess the effect of irinotecan on oxaliplatin pharmacokinetics and to determine the MDT of both drugs when administered in combination. Treatment was repeated every 2 weeks. Pharmacokinetic studies were performed on cycle 1 and 2 to assess the best sequence and detect any interaction between the two drugs. Thirty-four patients with advanced colorectal cancer were enrolled; 28 of them (82%) had liver involvement. The main toxicities were neutropenia and delayed diarrhea; 5 patients (14%) experienced febrile neutropenia. Dose-limiting toxicity was experienced at levels 1/2/3/4/5 by 4/10, 1/6, 3/6, 3/8, and 3/4 patients, respectively. Fifteen patients responded (2 CR; 13 PR) for an ORR of 44%. No pharmacokinetic interactions between irinotecan and oxaliplatin were detected. The recommended dose for future phase II trials is oxaliplatin 85 mg/m and irinotecan 180 mg/m2 on day 1 combined with 5FU/leucovorin according to the de Gramont regimen at days 2 and 3. Twenty-nine percent of patients underwent secondary hepatectomy with curative intent, and two of them are long-term disease-free survivors. It would appear that the dose and schedule defined by this trial could be proposed as front-line therapy for advanced colorectal carcinoma to establish rapid disease control and to permit patients to proceed to surgery.

Background The role of neoadjuvant chemotherapy for patients with multiple (five or more) bilobar hepatic metastases irrespective of initial resectability is still under scrutiny. The purpose of this study was to compare the outcome of hepatectomy alone with that of hepatectomy after neoadjuvant chemotherapy for multiple bilobar hepatic metastases from colorectal cancer. Methods Retrospective data were collected from 71 patients after hepatectomy for five or more bilobar liver tumours. The outcome of 48 patients treated by neoadjuvant chemotherapy followed by hepatectomy was compared with that of 23 patients treated by hepatectomy alone. Results Patients who received neoadjuvant chemotherapy had better 3- and 5-year survival rates from the time of diagnosis than those who did not (67·0 and 38·9 versus 51·8 and 20·7 per cent respectively; P = 0·039), and required fewer extended hepatectomies (four segments or more) (39 of 48 versus 23 of 23; P = 0·027). Multivariate analysis showed neoadjuvant chemotherapy to be an independent predictor of survival. Conclusion In patients with bilateral multiple colorectal liver metastases, neoadjuvant chemotherapy before hepatectomy was associated with improved survival and enabled complete resection with fewer extended hepatectomies.

Cystic diseases of the bile ducts are rare, but relatively more prevalent in females, and more common in Japan and Asia. Most are diagnosed in children under 10 years of age, with varying patterns of symptoms including right upper quadrant pain, jaundice, and fever. Up to 20% of bile duct cysts are diagnosed in adults, including during pregnancy, in whom the diagnosis can be confounded by associated cholelithiasis, or by abnormalities of the pancreatic junction with pancreatitis. The risk of malignant transformation increases with age, and is more common in cysts of Alonso-Lej Types I, IV, and V (Caroli's Disease). Intracystic lithiasis is frequently associated with tumour, and can give similar radiological appearances. Tumours are often first diagnosed at laparotomy, and can already be unresectable. More than half the tumours are intracystic, but malignant change in cyst mucosa without a tumour mass is often not recognised at surgery. In addition, malignant change in bile duct epithelium can occur after cyst excision, sometimes after many years, and in areas of the biliary tree remote from the cyst, including the gall-bladder. Cyst excision should be attempted at all ages, and patients closely monitored thereafter. Malignancy should be suspected in all adults with bile duct cysts. Hepatectomy, partial or total with transplantation, is the treatment of choice in Caroli's disease.

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.

Recurrence of hepatitis C after liver transplantation is common and can lead to severe liver diseases. Although immunosuppression and high levels of viremia suggest a direct pathogenicity of hepatitis C virus (HCV), the relations between viral replication and long-term histological course are still unknown. Thirty-three patients with a mean histological follow-up of 3.5 years (3 months - 8.6 years) were analyzed. Nineteen patients were infected by genotype 1b. Liver HCV RNA was determined in parallel with the quantitation of an internal control (28S ribosomal RNA) by competitive polymerase chain reaction (PCR). Lobular hepatitis (LH) and chronic active hepatitis (CAH) occurred in 27 and 19 patients, respectively. Levels of liver HCV RNA determined in 84 biopsies were higher in cases of LH than in the other patterns (82 +/- 123 vs. 19 +/- 38; P.01) and were unrelated to the genotype. Progression from LH to CAH was associated with a highly significant decrease of liver HCV RNA (P = .006), which was not observed in patients with stable histology. Among patients with CAH, those infected by genotype 1b had more severe liver damage and lower levels of liver HCV RNA than others (P = .04). Multivariate analysis showed that high levels of liver HCV RNA at the time of the first posttransplantation biopsy was an independent predictor of CAH (P = .01). After liver transplantation, the progression to CAH together with a decrease of liver HCV RNA suggests that a host's response is involved in the long-term viral pathogenicity. This response may be stronger and liver disease more severe in patients with high levels of replication at the time of LH and in those infected by genotype 1b.

TACROLIMUS was initially administered to liver transplant recipients as primary immunosuppressive therapy in conjuction with low-dose steroids at the University of Pittsburgh in 1989. Initial results indicated that tacrolimus was associated with significant improvements in patient and graft survival rates when compared with cyclosporine (CyA)-treated historical controls.1,2 Treatment with tacrolimus also resulted in marked reductions in the incidence of rejection and steroid requirements.2 Subsequently, two international, multicenter, prospectively-randomized, parallel-group trials were initiated (one in Europe and one in the United States) to evaluate and compare the efficacy and safety of tacrolimus- and CyA-based therapy. Results at 6,3–9 12,10–15 and 24 months16–18 have been published previously. This report addresses the continued follow-up of the European study with attention now focusing on 3-year data.

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).

Biostratigraphy of the AJbian of Koudiat el Beida (North of J. Mrhila, Central Tunisia). Biostratigraphic study of the Koudiat el Beida section, permitted to specify the Albian age of these series and to distinguish five lithostratigraphic terms, everyone characterized by one well-defined micropaleontological association (Foraminifera, Ostracoda and Algae). Systematic study of these microorganisms allowed the recognition of twenty species of planktonic Foraminifera, one hundred and thirty six species of benthic Foraminifera, forty species of Ostracoda and three species of Algae. These microfossils document an open marine environment, in an outer platform setting conditions (circalittoral) evolving progressively to deep water (epibathyal domain). The paleogeography of J. Mrhila region, is controlled by tectonics. Indeed, the outcrops of Koudiat el Beida shows that very thick basin sediments are deposited at North of Mrhila, pratically without interruption from the Clansayesian till the end of Albian times., L'analyse biostratigraphique de la coupe du Koudiat el Beida a per¬ mis de préciser l'âge albien de cette série et de distinguer cinq termes lithostratigraphiques caractérisés chacun par une association micro-paléontologique (Foraminifères, Ostracodes et Algues) bien déterminée. L'étude taxinomique de ces microorganismes a permis de répertorier vingt espèces de Foraminifères planctoniques, cent trente six espèces de Foraminifères benthiques, quanrante espèces d'Os-tracodes et trois espèces d'Algues. Ces microfossiles attestent d'un milieu marin ouvert, de faible profondeur (circalittoral) qui évolue progressivement vers un milieu plus profond dans le domaine épibathyal. La paléogéographie de la région du J. Mrhila, est contrôlée par la tectonique. En effet, les affleurements du Koudiat el Beida montrent que des sédiments très épais de faciès bassin se sont déposés au Nord du Mrhila, pratiquement sans interruption depuis le Clansayésien jusqu'à la fin des temps albiens., Zghal Ihsen, Bismuth H., Razgallah-Gargouri Saloua, Damotte Renée Rivière, Ben Hadjali N. Biostratigraphie de l'Albien du Koudiat el Beida (Nord du J. Mrhila, Tunisie centrale). In: Géologie Méditerranéenne. Tome 23, numéro 1, 1996. pp. 27-61.

The ability of a three-electrode capacitive heating device operating at 13.56 MHz to produce and effect spatial redistribution of hyperthermic temperatures is demonstrated through abdominal heating studies conducted with 80 kg female and 65 kg male pigs. Temperature-time profiles over the respective heating periods were obtained in anterior and posterior superficial tissue and in selected abdominal organs. At selected times during heating, spatial redistribution of elevated temperatures was effected through adjustment of power settings for one or more of the three electrodes, i.e. through manipulation of the specific absorption rate (SAR) in-vivo.

We report the clinical and biological course of infection with human immunodeficiency virus (HIV) type 1 in 11 liver transplant recipients who acquired this infection between 1985 and 1987. Eight patients were infected by blood or blood products from graft-related transfusions and one by the graft itself; the remaining two patients were infected after transplantation and had independent risk factors. All patients received a triple-drug immunosuppressive regimen including cyclosporine. The mean duration of follow-up after liver transplantation was 52 months (standard error, +/- 32 months). Chronic graft rejection was documented in four cases. The cumulative incidences of HIV-related complications and HIV-related deaths were 82% and 27%, respectively. Three patients died rapidly of HIV disease. The survival rate 7 years after transplantation was 36% among the 11 HIV-infected patients, whereas it was approximately 70% among HIV-negative liver transplant recipients during the same period. The course of HIV infection in the four survivors did not appear to differ from that in other patients infected by blood transfusion.

The aim of this prospective nonrandomized study was to assess the immediate and short-term sequelae of transjugular intrahepatic portosystemic shunting on the circulatory hyperdynamic state of the cirrhotic patient. Twelve transjugular portosystemic shunting procedures were performed in 12 cirrhotic patients for sclerotherapy failure (10 cases) and/or intractable ascites (4 cases). Self-expandable stents 10 mm in diameter were used in all cases. Portal pressure measurement and right-heart catheterization were performed before and 30 min and 1 mo after the procedure. The portoatrial pressure gradient decreased from 15 +/- 3 to 7 +/- 3 mm Hg 30 min after surgery (p < 0.0001) to 8 +/- 3 mm Hg 1 mo after surgery (p < 0.001, in comparison with basal values). The cardiac index increased from 4.5 +/- 1.3 to 5.7 +/- 1.5 L/min.m2 30 min after surgery (p < 0.001) to 7.4 +/- 1.4 L/min.m2 1 mo after surgery (p < 0.001). Systemic vascular resistance decreased from 808 +/- 323 to 646 +/- 209 dyne.sec.cm-5 30 min after surgery (p < 0.01) to 467 +/- 101 dyne.sec.cm-5 1 mo after surgery (p < 0.05). This study demonstrates that transjugular portosystemic shunting rapidly and significantly worsens the hyperdynamic circulatory state of the cirrhotic patient. Although apparently noninvasive, this procedure should be considered with caution in cirrhotic patients with limited cardiac reserve.

The dramatic development of liver transplantation compared to a relative shortage of donors has brought a renewed interest to xenotransplantation. Because of anatomical and immunological compatibilities, nonhuman primates are the most appropriate donors. The aim of this work was to analyze the different problems of a baboon-to-man liver xenotransplantation. Thirty baboons bred in a French Primatology Center were studied. The analysis of anatomical, microbiological, and immunological data showed that only 8 baboons out of 30 were suitable as donors for xenotransplantation. Considering these data and the ethical issues, the actual feasibility of xenotransplantation programs is discussed.

New data from Cretaceous and Eocene series in the area of Grombalia (North Eastern Tunisia). Due to its geographical position on the border of the Grombalia graben and on the septentrional extension of the North-South chain, this studied area has deeply recorded the influence of those directions. Thus in this area, the Upper Cretaceous is characterized by thicknesses reductions and sedimentary hiatuses, and also by a remarkable thickening of the Cretaceous series towards the Grombalia graben. The Cretaceous sedimentation control by the N 140 -N 160 faults is marked by a structuration in horsts and grabens. From a biostratigraphical point of view within this study, many precisions are brought on the Cretaceous and Eocene series of the North-Eastern Tunisia and on their microfaunal content. The general hiatus of the whole Turanian -Lower Senonian series previously supposed is shown to be a wrong notion. At the top of the Kef Formation, a new lithostratigraphical unit of Santonian age, called «Membre El Mekki», is defined., Le secteur étudié, de par sa position géographique en bordure du Fossé de Grombalia et dans le prolongement septentrional de la Chaîne Nord-Sud, a profondément enregistré, au Crétacé supérieur, l'influence de ces deux directions. C'est ainsi que la série est caractérisée d'une part par des réductions d'épaisseurs et lacunes sédimentaires, d'autre part par un épaississement notable en direction du Fossé de Grombalia. Le contrôle de la sédimentation crétacée par des accidents orientés N 140 à N 160 est marqué par l'installation de domaines tantôt subsidents, tantôt à sédimentation réduite, voire localement absente. Sur le plan biostratigraphique, ce travail apporte des précisions à la connaissance des séries crétacées et éocènes de la Tunisie nord-orientale. Ces précisions infirment la notion de lacune généralisée de toute la série du Turonien-Sénonien antérieurement admise. Au sommet de la Formation Kef, une nouvelle unité lithostratigraphique, d'âge santonien, dénommée «Membre El Mekki» a été définie., Ouahidi Ali, Bismuth H., Turki Mohamed Moncef. Nouvelles données sur le Crétacé et l'Eocène des environs de Grombalia (Tunisie nord-orientale). In: Géologie Méditerranéenne. Tome 20, numéro 1, 1993. pp. 25-43.

Background The optimal surgical strategy for patients with synchronous colorectal liver metastases (CLMs) is still unclear. The aim of this study was to compare simultaneous colorectal and hepatic resection with a delayed strategy in patients who had a limited hepatectomy (fewer than three segments). Methods All patients with synchronous CLMs who underwent limited hepatectomy between 1990 and 2006 were included retrospectively. Short-term outcome, overall and progression-free survival were compared in patients having simultaneous colorectal and hepatic resection and those treated by delayed hepatectomy. Results Of 228 patients undergoing hepatectomy for synchronous CLMs, 55 (24·1 per cent) had a simultaneous colorectal resection and 173 (75·9 per cent) had delayed hepatectomy. The mortality rate following hepatectomy was similar in the two groups (0 versus 0·6 per cent respectively; P = 0·557), but cumulative morbidity was significantly lower in the simultaneous group (11 per cent versus 25·4 per cent in the delayed group; P = 0·015). Three-year overall and progression-free survival rates were 74 and 8 per cent respectively in the simultaneous group, compared with 70·3 and 26·1 per cent in the delayed group (overall survival: P = 0·871; progression-free survival: P = 0·005). Significantly more recurrences were observed in the simultaneous group at 3 years (85 versus 63·6 per cent; P = 0·002); a simultaneous strategy was an independent predictor of recurrence. Conclusion Combining colorectal resection with a limited hepatectomy is safe in patients with synchronous CLMs and associated with less cumulative morbidity than a delayed procedure. However, the combined strategy has a negative impact on progression-free survival.

The tolerance of the liver to ischaemia during intermittent clamping of the hepatic pedicle was compared with that during a continuous Pringle manoeuvre. Three groups of rats undergoing total durations of clamping of 60, 90 and 120 min were studied. A temporary peroperative portacaval shunt was used to exclude the efects of splanchnic venous stasis and allow independent study of the efects of hepatic ischaemia. In each group, three methods of portal clamping were evaluated: a continuous Pringle manoeuvre (n = 10), a 30-min intermittent clamping (n = 10) and a 15-min intermittent clamping (n = 10). The clamp release time between the periods of liver ischaemia was 5 min. Survival at day 7 and postoperative changes in liver function (transaminase enzymes, bilirubin, bromsulphthalein elimination, liver adenosine 5′-triphosphate levels) were recorded. Intermittent clamping of the pedicle was tolerated significantly better than continuous clamping. This method optimizes the ability of the liver to tolerate extended periods of ischaemia. For a given duration of ischaemia, no additional improvement could be produced by shortening the intermittent clamping period from 30 to 15 min. These data suggest that, when the Pringle manoeuvre is used, it should be applied intermittently rather than continuously.

We have investigated hepatitis C virus (HCV) viremia before and after orthotopic liver transplantation (OLT). 38 patients were examined; 16 were anti-HCV positive and 22 anti-HCV negative pre-OLT in a RIBA-2 test (Ortho Diagnostic Systems Inc., Westwood, MA). HCV-RNA was detected using a modified nested polymerase chain reaction in 14/38 and 10/38 patients before and after OLT, respectively. 7 of these 14 subjects who were HCV-RNA positive before OLT were also positive for serum hepatitis B surface antigen. After OLT, six patients became HCV-RNA positive, likely as a result of transfusions, while four developed a probable recurrence of HCV infection. Infection of the liver graft by the same strain of HCV was indeed demonstrated by sequence analysis of a hypervariable domain (in the envelope region) in two cases. This establishes the possibility of HCV recurrence and shows the usefulness of polymerase chain reaction as the only assay currently capable of identifying HCV infection after OLT.

Controversy surrounds the indication of liver transplantation in patients with hepatitis B virus infection. The major problem is the very high risk of infection of the graft. Some investigators have suggested that the presence of HBsAg is a contraindication to liver transplantation. Between February 1975 and December 1990, 178 HBs positive patients were transplanted at Paul Brousse Hospital in Professor H. Bismuth's Department, 137 for post hepatitis cirrhosis and 41 for fulminant hepatitis. Since April 1984 we have decided long term immunoprophylactic therapy for all patients with HBs infection. But only from August 1987 our supply of purified anti HBs immunoglobulin has been adequate to treat all our patients according to the following protocol: 10.000 IU during the peroperative phase, 10.000 IU immediately after intervention, 10.000 IU every day for the first 6 days, 10.000 IU when the anti HBs levels were under 150 IU/l. One hundred thirty-nine patients were treated by this method. 110 cleared HBs antigen from their sera and their liver were biologically and histologically free of B virus infection. 29 patients showed reappearance of HBs antigen in their sera and nearly all of them developed objective, histologically confirmed, graft lesions. These lesions are those of classical infection: acute hepatitis, active chronic hepatitis and cirrhosis. So 79% of patients were successfully treated with a follow up of 45 months to 6 months. We also studied the prognostic factors under treatment. The study shows: in the case of fulminant hepatitis, 93% success versus 77% in post hepatitis cirrhosis; in the case of Delta superinfection, 94% success versus 66% with pure B infection; in the absence of HBVDNA in the patient's sera before transplantation, 92% success versus 20% in the presence of HBVDNA. For a better understanding of the overall results, the two following parameters have to be considered: some patients relapsed after stopping their treatment, some other patients, despite repositivation of HBs antigen in their sera showed a paradoxal good evolution. These considerations enable us to obtain HBVDNA positive patients: 10% success, HBVDNA negative patients: Fulminant hepatitis: 100% success B Delta post hepatitis cirrhosis: 100% success B post hepatitis cirrhosis: 92% success.

Over a 10-year period from 1980, 46 patients with liver injuries were referred after primary admission to other hospitals. Previous surgery had been performed in 40 cases and the predominant reasons for referral were uncontrollable bleeding and postoperative sepsis with biliary leakage. Of 30 such cases, 19 were treated by liver resection; all were of a limited nature and no major hepatectomies were performed. Only two deaths occurred in these patients and this low mortality rate supports our conservative approach to liver trauma. Other reasons for referral were late biliary stenosis, complicated penetrating injury and intrahepatic haematoma. Three cases were referred with postoperative hepatic failure; two responded to resection of infected necrotic tissue and liver transplantation was attempted in the third. Injuries to liver segments 6 and 7 were those most frequently referred for assistance with bleeding, and all patients were safely transferred after intra-abdominal packing. This injury is particularly suitable for resection by segmentectomy rather than a formal hepatectomy, which has been associated with a high mortality rate in trauma cases. Further patients with intractable injuries might be salvaged by liver transplantation.

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.

The evolution of surgery

Objective: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting. Background: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors. Methods: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patient's characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. Results: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2-13 days). At a mean follow-up of 13 months (median, 10 months; range, 2-58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD. Conclusions: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.

The feasibility of splitting the liver prior to transplantation depends on the surgical application of the anatomical segmentation of the liver, as described by Couinaud [1]. The technique was first described by Pichlmayr in 1988 [2] in an adult and a child. Extending its use together with that of liver reduction techniques (in which a large volume of healthy liver may be discarded) [3], and increasing experience have considerably reduced the number of children awaiting liver transplantation [4]. However, the number of patients waiting for a liver to be transplanted increases as new indications are added and makes the scarcity of available organs more and more serious; with adult potential recipients accounting for >95% of the waitinglist deaths [5].

The reliability of splitting livers for transplantation into two adult recipients remains to be proven. The aim of this paper was to report our experience with such splitting in two adults. Ex situ and in situ splitting were performed in 15 and 2 cases, respectively, generating 34 grafts (30 transplanted in our center, 4 shipped to two partner centers). Cold ischemia time, intraoperative transfusion volume, and hospitalization stay were comparable for recipients of left and right grafts. Within 15 days of transplantation, liver function tests were significantly better for recipients of right grafts than for recipients of left grafts. Primary nonfunction occurred in three cases and was statistically related to the presence of a graft/body weight ratio (GBWR) of < 1% (P < 0.001). Eleven technical complications occurred in eight patients (morbidity rate 24%) including biliary stenosis (four cases); biliary leak and portal vein thrombosis (two cases each); hepatic artery stenosis, subphrenic abscess, and hemoperitoneum (one case each). These complications led to graft loss in three cases, with death resulting in two. After a mean follow-up of 34 months, 24 of 34 patients are alive with normal liver function tests. Actuarial 1-year patient and graft survival rates were, respectively, 80% and 74% for the whole series. Actuarial 1-year patient and graft survival rates for right and left grafts were not statistically different (72% vs. 87% and 72% vs. 76% respectively).

When I speak about complications related to liver transplantation with a patient, I never mention the main complication of liver transplantation — being not transplanted. According to UNOS a significant number of patients on the waiting list will have to wait longer than two years, which is unacceptable. It means, depending on the indication, that many of these patients will have to die. And due to expansion of indication and shortage of organs, mortality on the waiting list continuously rises. In Europe the number of liver transplantations has plateaued for about four years now. That means we cannot expect expansion of the numbers of donors in the next few years. So the only answer to this dilemma — beyond improving the liver transplantations in our patients we perform today — is shown in Fig. 1. It is a slide in a lecture one might give in 3 to 4 years routinely showing that a donor has to give 2 lungs, 1 heart, 2 kidneys and 2 livers. For many years, anatomy has already been talking about two livers. One speaks of removing the right liver or the left liver. Yet this is not anchored enough in the mind of the liver transplant surgeon. Today we must think of the liver as source for two liver grafts as a standard concept. The donor has to be considered as one with two livers and both have to be allocated like other paired organs. As reported by Azoulay et al. (1996), de Ville de Goyet et al. (1999) and Busuttil et al. (1999), the liver is a splitable organ in about 30% of the cases. So the first step is to define the donor that is ideal for splitting. Basic characteristics for the ideal donor would be an age of less than 60 years and more than 70 kg of body weight. There should be no history of cardiac risk and the donor should be in a dynamically stable condition with no or minimal vasopressors. The liver should be free of steatosis and the presumed liver weight should be above 1.8 kg. A donor like this should be reported to the allocating organization as a donor with two livers. To minimize organizational problems due to the fact that one has to deal with two recipient centers, surgical techniques to split the liver need to be standardized. The right liver should be the one without the vena cava, with the right hepatic vein only (no middle vein) and with part of the right pedicle. There is a lot of experience with this approach especially from living-related donation as reported by Professor Tanaka.

This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.

The aim of the study was to determine whether clear cell type hepatocellular carcinoma should still be regarded as a separate uniform diagnostic entity.We retrospectively studied 118 cirrhotic patients with hepatocellular carcinoma treated by orthotopic liver transplantation, and 31 noncirrhotic patients with hepatocellular carcinoma treated by either liver surgical resection or transplantation. The pathology of all liver resections was reviewed. Microsatellite instability was performed on paraffin-embedded samples at loci located on chromosomes 2p, 3p, 5q, 8q, 9p, 13q, 16q and 17p. Among the 118 cirrhotic patients, 10 (8.5%) had a clear cell hepatocellular carcinoma; these had clinical characteristics and prognosis similar to the other cirrhotic patients. No genetic alterations were detected in these tumours. Among the 31 noncirrhotic patients, one (3.2%) had a clear cell hepatocellular tumour. This 170-mm tumour had a lipid density on computed tomography, and its histology resembled chromophobe cell renal carcinoma. Furthermore, this tumour had unusual genomic alterations, with microsatellite instability in 6/8 chromosome loci.Clear cell hepatocellular carcinoma is a heterogeneous entity in which a chromophobe cell subtype should be identified.

Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma.Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameteror = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04).Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.

Severe veno-occlusive disease (VOD) of the liver is a leading cause of mortality after bone marrow transplantation (BMT). Vascular and parenchymal injuries account for acute portal hypertension and liver failure is frequently present. We describe the results of transjugular intrahepatic portosystemic shunt (TIPS) for the management of VOD after BMT. TIPS was performed in 10 patients with histologically proven severe VOD. Portal hypertension was controlled by TIPS in all patients (mean hepatic venous pressure gradient before, 20 +/- 11 vs 6 +/- 5 mm Hg after TIPS, P0.01) without technical complications. Five patients with rapidly worsening VOD died within 10 days of TIPS without any improvement. The five remaining patients with less advanced disease showed improvement in various clinical and biological parameters. Four patients subsequently died. The lone survivor continues to do well with resolution of VOD 6 months after TIPS. TIPS can be performed safely and controls portal hypertension in VOD after BMT. Arguments from the present series and from eight previously reported cases favour earlier application of TIPS to obtain improved overall survival. Bone Marrow Transplantation (2000) 25, 987-992.

Portal vein thrombosis was considered to be a major contraindication to liver transplantation before the introduction of vessel grafts from the recipient's area of confluence of the splenic and superior mesenteric veins, behind the neck of the pancreas, to the graft's portal vein. Refinement in surgical technique has given rise to a large number of possibilities to overcome portal vein thrombosis in OLT recipients, ranging from portal vein thrombectomy to several different venous graft jump reconstructions. All these reconstructions require the presence of a patent vein of the portal system. When neither splanchnic veins nor sufficiently large venous collaterals are available, liver transplantation has been considered impossible. Salvage solutions include arterialization of the portal vein with the associated risk of liver damage in the longterm, a combined liver and bowel transplantation has been proposed but not yet reported (and in any case the results of combined liver and bowel transplants are not as good as those of liver transplantation alone) and finally the use of blood inflow from the inferior vena cava as first reported by Tzakis and coworkers. Portal flow from the inferior vena cava may be performed as a last resort. Although the consequences of severe pretransplantation portal hypertension remain and should be treated before, during, and after transplantation, liver function is normal in the short and midterm. With this new procedure, diffuse portal vein thrombosis is no longer an absolute contraindication to liver transplantation. But this needs to be confirmed in light of further experience and longterm followup.

Disseminated histoplasmosis in immunosuppressed patients rarely occurs in nonendemic areas. Reported here is a case of disseminated histoplasmosis in a patient who had undergone orthotopic liver transplantation and had never traveled outside of France. The infection was most likely transmitted via the liver allograft, since the organ donor had lived in an area highly endemic for the disease (French Guiana) 20 years earlier. Two years post-transplantation, none of the other patients who received allografts (heart, cornea, kidneys) from the same donor had developed signs of infection.