INTRODUCTION:The advanced age of the recipient is considered a "relative contraindication" to liver transplantation (LT). However, recently some studies reported a morbidity rate and an overall survival comparable with those of younger patients. Here, we reported the outcome after LT in recipients aged >65 yr.METHODS:Between January 2000 and December 2006, 565 LT was performed in 502 recipients in our institution. Of these, 34 were recipients of >65 yr old (aged group). We focused our study comparing: donor age, co-morbidities, model for end-stage liver disease (MELD) and American Society of Anesthesiologists (ASA) score, duration of operation, transfusions and outcome between the two groups (young/aged).RESULTS:For the group aged >65: the mean donor age was 52.5 (range 16-75) yr and the graft weight 1339 g (890-1880 g). Co-morbidity was recorded in 25 (73.5%), coronary artery disease (CAD) in 17 (50%), diabetes mellitus (DM) and chronic renal insufficiency in four (11.7%) and chronic obstructive pulmonary disease (COPD) in three patients (8.8%). Mean MELD score was 14.9 (range 12-29) and ASA score was two in 15 (44.1%); and three in 19 (55.8%) recipients. Mean operation time was four h 45 min, three patients also received combined kidney transplantation. Twenty-five (73.5%) recipients received blood transfusions (mean 3.2). Morbidity was observed in 20 patients (58.8%); of these two had hepatic artery thrombosis requiring re-LT. Overall survival was 80% (40 months of follow-up), in particularly, at 30-d, one yr, three yr was 91%, 84%, 80%, respectively. The only two statistical differences reported (p = 0.02) are: the lower rate of CAD in the younger group of recipients (12%), compared with the aged group (50%) and the subsequently lower mortality rate secondary to cardiac causes in the younger group (1.4%) compared with aged group (8.8%).CONCLUSION:Our results suggest that the recipient age should not be considered an absolute contraindication for LT when the graft/recipient matching is optimal and when an adequate cardiac assessment is performed.

The response rate of colorectal metastases to chemotherapy, ranging from 50 to 60%, has been shown to be a prognostic factor. Complete pathologic and radiological response rates are approximately 4 and 7%, respectively. Hepatotoxic effects of oxaliplatin and irinotecan on the non-tumoral liver parenchyma have been reported and are incriminated in vascular changes (sinusoidal obstruction syndrome [SOS]) and chemotherapy-associated steatohepatitis (CASH). Oxaliplatin-based regimens are associated with an increased risk of vascular lesions and irinotecan-based regimens are associated with increased risks of steatosis and steatohepatitis. SOS increases morbidity after major liver resection, mostly after administration of more than six cycles of neoadjuvant systemic chemotherapy. CASH increases morbidity and mortality rates after hepatectomy. Preliminary results have shown that the addition of targeted molecular therapy (bevacizumab or cetuximab) to conventional chemotherapy does not increase the postoperative morbidity or mortality rates after hepatectomy and does not create additional injury to the non-tumoral liver parenchyma. However, bevacizumab may impair regeneration of the future remnant. Chemotherapy may reduce the sensitivity of CT scan and PET scan in the detection of metastases.

Le but de cette étude était d'évaluer les résultats des résections pancréatiques associées à une résection artérielle (RA) pour le traitement chirurgical des adénocarcinomes du pancréas localement avancés. Entre janvier 1990 et décembre 2008, 26 patients ont eu une pancréatectomie avec résection artérielle à visée curative et ont été appariés à 26 patients, parmi l'ensemble des patients qui ont eu une pancréatectomie dans notre centre (n = 1136), selon des critères d'âge, de sexe, de la période d'étude, du statut ganglionnaire, de l'invasion péri-neurale et de la nécessité d'une résection veineuse associée.Vingt quatre patients ont eu une duodénopancréatectomie céphalique, 18 une pancréatectomie totale et 10 une splénopancréatectomie gauche. La mortalité postopératoire était de 5,7 % et la morbidité de 41,6 %. Le taux de survie globale à 3 ans était de 22,1 % avec une médiane de 17 mois dans le groupe avec résection artérielle (RA+) versus 17,6 % avec une médiane de 12 mois dans le groupe sans résection artérielle (RA-) (p = 0,581).Quatre patients dans le groupe RA+ ont eu une survie supérieure à 4 ans. L'analyse multivariée montrait que l'envahissement de la paroi de l'artère, le nombre de ganglions réséqués < 15 et l'invasion péri-neurale étaient des facteurs pronostics indépendants de survie. Les résections pancréatiques avec RA pour le traitement des adénocarcinomes localement avancés du pancréas permettent d'obtenir un taux de survie à 3 ans équivalent aux résections pancréatiques sans RA.

AIMS:To analyse the effects of the preoperative targeted molecular therapy (cetuximab (cetu) or bevacizumab (beva)) on non-tumorous liver parenchyma, and the clinical and biological outcome after liver resection for colorectal liver metastases (CLM). METHODS:Between January 2005 and December 2007, 36 patients receiving preoperatively cetu (n = 15) or beva (n = 21) were, respectively, matched to a control group of patients who did not receive targeted molecular therapy. They were matched on the basis of age, gender, body mass index, extent of hepatectomy, and type and number of neoadjuvant chemotherapy. Liver function tests, postoperative outcome and histopathology of the resected liver were compared. RESULTS:There was no mortality. Postoperative morbidity and perioperative bleeding rates were similar in both groups. In the beva group, liver function tests showed higher serum bilirubin level on postoperative day (POD) 1 (p = 0.001) and POD 3 (p = 0.01), higher serum aspartate aminotransferase on POD 1 (p = 0.004), and lower prothrombin time on POD 5 (p = 0.02). In both groups, cetu and beva, the postoperative peaks of gamma-glutamyl transpeptidase and alkaline phosphatase were statistically higher than in the control groups. Interestingly, the prevalence of sinusoidal injury and fibrosis was lower in patients receiving cetu (p = 0.04), while the prevalence of steatohepatitis was lower in patients receiving beva (p = 0.04). CONCLUSION:The addition of beva or cetu to the neoadjuvant chemotherapy regimens does not appear to increase the morbidity rates after hepatectomy for CLM. The pathological examination did not show additional injury to the non-tumorous liver parenchyma.

L'âge > 65 ans est habituellement considéré comme une contre-indication à la transplantation hépatique (TH). Cependant, des études récentes ont rapporté des résultats similaires en termes de complication et de survie que pour une TH chez des receveurs jeunes. De janvier 2000 à décembre 2006, tous les dossiers des TH ont été revus de façon rétrospective : 37 TH ont été réalisées chez des patients > 65 ans. L'âge moyen des donneurs était de 52,5 ans et le poids moyen du greffon était de 1 339 g (890-1 880 g). Une comorbidité était présente chez 25 receveurs (73,5 %) : coronaropathie (n = 17 ; 50 %), diabète (n = 4 ; 11,7 %), une insuffisance rénale chronique (n = 4 ; 11,7 %), et BPCO (n = 3 ; 8,8 %). Un antécédent de chirurgie hépatique (n = 2) ou pulmonaire (n = 1) était retrouvé. Le score MELD moyen était de13,9 (extrêmes : 7-29) et le score ASA était de 2 chez 15 (44,1 %) et de 3 chez 19 (55,8 %) receveurs. La durée moyenne d'intervention était de 4h45 min. Une transplantation rénale combinée était réalisée chez 3 patients. Une transfusion était nécessaire lors de 25 TH (73,5 %) avec un nombre moyen de 3,2 culots globulaires transfusés. Le taux de mortalité était de 8,8 % : 3 patients ASA 3 avec un score MELD de 11, 14 et 17. Une complication était observée chez 20 patients (58,8 %) : 2 patients ont eu une thrombose de l'artère hépatique nécessitant une nouvelle TH. La survie global des patients (avec un suivie moyen de 40 mois), était respectivement à 30 jours, 1 an et 3 ans de 91 %, 84 %, 80 %. Nos résultats suggèrent que l'âge > 65 ans ne doit plus être considéré comme une contre-indication à la TH surtout lorsqu'il existe une bonne adéquation avec le greffon.

Background: Malignant periampullary tumours often invade retroperitoneal peripancreatic tissues and a positive resection margin following pancreaticoduodenectomy (PD) is associated with a poor survival.The margin most frequently invaded is the retroperitoneal margin (RM).Among the different steps of PD one of the most difficult and less codified is the resection of the RM with high risk of bleeding.We have developed a surgical technique -"Hanging maneuver" -which allows at the same time a standardization of this step, a complete resection of the RM, and an optimal control of bleeding.Patients/Methods: We described the surgical technique, and we reported our preliminary experience.Surgical data, postoperative outcome and pathological results of patients submitted to PD for pancreatic carcinoma using "Hanging maneuver" technique between January 2007 and December 2007 were reviewed. Results:The Hanging maneuver was performed in 20 patients without any intra-operative complication and massive bleeding.No patient required blood transfusion.After had inked the surgical margins, retroperitoneal peripancreatic tissue was invaded in 12 out of 17 patients with malignant diseases (70.5%).In only one case (6%), the retroperitoneal margin was involved by the tumour (R1 resection).Conclusion:.The "hanging maneuver" is a useful and safe technical variant and should be considered in the armamentarium of the pancreatic surgeons in order to achieve negative retroperitoneal margins.

Background: Advanced age is considered a contraindication to transplantation at most centres.Although studies of liver transplantation recipients have demonstrated that the incidence of complications and overall survival are similar to those of younger.Our aim was to analyzed the outcome after transplantation in patients over 65.Methods: Between January 2000 and December 2006, 37 OLT was performed in 34 patients >65 years (range 66-72) at the University of Strasbourg.We analysed demography characteristics, Child and MELD score, donor age, graft weight, whole graft and ischemic time, indications, ASA and comorbidities, duration of operation, number of transfusion, immunosuppression therapy and complication.Routine cancer screening among potential graft recipients involved measurement of tumours markers, colonoscopy and cervical and breast cancer.Results: The indications for transplantation was HCC (55.8%), cirrhosis due to hepatitis C and alcohol (11.7%),PBC and retrasplantation (5.8%), cholangiocarcinome, endothelial hemangioma and hepato-pulmonary syndrome (2.9%).Donor age was 52.5 (±16.75) and graft weight 1339 gr (890-1880).Comorbidity was reported in 25 patients (73.5%),CAD in 17 (50%), IDDM and CRI in 4 (11.7%),COPD in 3 (8.8%)and liver or pulmonary surgery in 2 and 1 case respectively.MELD score was 13.9 (range 7-29) and ASA score were 2: 15 (44.1%); 3: 19 (55.8%).Mean operation time was 4h 45 min, 3 patients received combined kidney transplantation.CIT was in 19 (51.4%) <600 minutes, in 12 (32.4%)>600 and in 6 (16.2%) >1000.25 (73.5%)patients received blood with average 3.2 U.I..The immunosuppression was done according to the era protocols: initially CSA and the later TAC-based therapy.Overall mortality was 8.8% with ASA 3 and MELD 11, 14, 17 respectively.Morbidity was observed in 20 patients (58.8%);surgical complications were observed in 6 patients (17.6%), of these 2 hepatic artery thrombosis required retrasplantation.The ICU Hospital stay was of 4.8 and mean hospitalisation of 19.1 days.Patient overall survival was 76.4% (37.6 months of follow-up) in particularly at 30-days, 1-yr, 3-yr was 91%, 84%, 77%, respectively.Conclusion: our results indicate the age should not be considered an absolute contraindication for OLT 226

This paper highlights our experience of the transfer of hydrodynamic gene therapy (HGT) from the large animal, the pig, into clinical practice. The modification of balloon catheters and the development of a minimally invasive technique to allow selective isolation of liver segments for HGT in the large animal and human are described. Finally, our preliminary results from a phase I clinical study of HGT for thrombopoietin (TPO) in cirrhotic patients with thrombocytopenia are discussed. Based on these provisional data, minimally invasive selective HGT of liver segments appears to be technically safe, but further work is required to optimize the efficiency of gene transfer in order to achieve clinical benefit.

INTRODUCTION:Despite the well-known controversies about split-liver procedures, since 1979 we have utilized an ex situ instead of an in situ technique because of its feasibility. However, we sought to prove the equality of the results of these two procedures. Herein, we have presented our experience after 27 years' follow-up.MATERIALS AND METHODS:Between March 1979 and June 2006, we transplanted 84 livers in 67 pediatric recipients including 37 ex situ split livers implanted into 28 patients.RESULTS:We recorded demographic characteristics, transplantation, and retransplantation indications, age difference between donors and recipients, comorbidities, cold ischemia times, surgical times and complications, graft/recipient body weight ratios, organ recovery times, and overall survivals after 1, 5, and 15 years follow-up. We have herein reported 1, 5, and 15 years of patient versus organ survivals of 88.9.1%, 84.5%, 62.1% versus 78.6%, 74.2%, 57.4%, respectively.CONCLUSION:We have concluded that an ex situ split liver may be a valid alternative to in situ techniques to achieve good grafts for pediatric transplantation.

Poly(ethylene oxide) (PEO) hydrogels were synthesized directly in water or physiological medium by free radical homopolymerization of telechelic PEO macromonomers. Their ability to serve as semi-permeable, biocompatible membranes for an artificial pancreas was examined. In vitro tests confirmed their good biocompatibility. Both glucose and insulin diffuse through these hydrogels but the behavior of the latter is more complex. The crosslinking reaction could be extended to include direct encapsulation of biologically active materials such as hepatocytes.

The life expectancy of elderly patients over 70 years old is currently estimated around 12 years. Hepatobiliary and pancreatic resection constitute the only available curative treatment for liver or pancreatic carcinomas. Between 1990 and 2003, in our experience, a total of 131 elderly patients of more than 70 years were operated on for hepatic or pancreatic malignant tumours. These resections were carried out with a mortality similar to that observed among patients younger than 70 years old. The median survival is 33 months after resection of colo-rectal liver metastases and 20 months after pancreatic resection for malignant tumour. These results suggest that an age higher than 70 years no longer constitutes a contra-indication to a curative hepatic or pancreatic resection.

Cirrhosis due to chronic infection by hepatitis C virus (HCV), associated or not to a primary hepatocarcinoma, has become the first indication of liver transplantation. Graft reinfection by HCV is considered to be systematic while its prognosis is variable from one patient to another. A better knowledge of factors implicated in the occurrence and severity of hepatitis C recurrence is crucial in order to make optimal patients' monitoring. This article aims to present available data in this field, clarifying the role of viral factors (viral load, genotype, evolution of viral quasispecies) and host-related factors (immune response) which could take part in the development of hepatitis C recurrence.

Various incubation conditions of human hepatocytes were compared for their accuracy in predicting the in vivo hepatic clearance (CL(H)) of model compounds. The test compounds were the highly cleared, low protein bound naloxone (in vivo CL(H) = 25 ml min(-1) kg(-1); free fraction = 0.6), the medium clearance, highly protein bound midazolam (CL(H) = 12 ml min(-1) kg(-1); free fraction = 0.04) and the low clearance, highly protein bound bosentan (CL(H) = 3.9 ml min(-1) kg(-1); free fraction = 0.02). Each compound was tested in three 'hepatocyte systems', using resections from three donors, in the presence and absence of human serum. Those hepatocyte systems were: conventional primary cultures, freshly isolated suspensions and cryopreserved suspended hepatocytes. Except for a twofold overestimated CL(H) for bosentan from conventional primary cultures, and despite variable cryopreservation recoveries, similar predictions of CL(H) were recorded with all hepatocyte systems. Moreover, the CL(H) values obtained with cryopreserved suspended hepatocytes were similar to those obtained with freshly isolated suspensions. For midazolam and bosentan, the predicted in vivo CL(H) was markedly higher in the presence of serum, whereas serum had little influence on the scaled-up CL(H) of naloxone. In vivo, CL(H) was properly approached for naloxone and bosentan (particularly from experiments in the presence of serum), but it was strongly underestimated for midazolam (particularly in the absence of serum). Additional compounds need to be investigated to confirm the above findings as well as to assess why the clearances of some highly protein-bound compounds are still considerably underestimated.

INTRODUCTION:Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) rarely develops in patients with solid organ transplantation.PATIENTS AND METHOD:We describe the clinical, biological, electrophysiological and neuropathological features of 4 patients with solid organ transplantation who developed CIDP. Two patients had liver transplantation, one had kidney transplantation and one had lung transplantation.RESULTS:All 4 patients developed in the months following transplantation a syndrome that fulfilled criteria for definite CIDP. All patients had immunosuppressive therapy, with ciclosporin + prednisolone in 2 cases, tacrolimus in 1 case and azathioprine + prednisolone + ciclosporin in one case. One patient had chronic HCV and HBV infection. Treatment with intravenous immune globulin (IVIG) and/or a change in immunosuppressive therapy improved the neuropathy in all cases.CONCLUSION:CIDP is a rare and potentially treatable condition that should be considered in all patients with solid organ transplantation who develop a rapidly disabling sensorimotor polyneuropathy.