Bertrand Suc

Duodénopancréatectomie céphalique pour cancer

Duodenopancreatectomie cephalique pour cancer M. Huguier, A. Barrier, C. Gouillat, B. Suc, D. Jaeck, B. Launois De nombreuses propositions ont ete faites pour ameliorer les resultats de l’operation de Whipple. Des etudes prospectives controlees (essais), des meta-analyses ou, a defaut, des etudes retrospectives permettent d’evaluer ces propositions. Les pancreatectomies totales et les curages cellulo-lymphatiques etendus ne semblent pas ameliorer les durees de survie des malades dans des comparaisons retrospectives ou dans des essais. Un envahissement veineux apparent, mesenterique superieur ou portal, ne contre-indique pas a lui seul une exerese dont les resultats sont similaires a ceux observes lorsqu’il n’existe pas d’envahissement. Des essais et une meta-analyse n’ont montre ni avantages ni inconvenients majeurs a la conservation antro-pylorique. Trois essais et une meta-analyse n’ont pas montre que l’anastomose pancreatico-gastrique diminuait le risque de fistule par rapport a l’anastomose pancreatico-jejunale. Deux essais suggerent que, pour la realisation de celle-ci, l’intubation du pancreas dans le jejunum ou le drainage externe temporaire du canal de Wirsung diminuraient ce risque de fistule ce qui, pour cette seconde technique, n’a pas ete confirme par un autre essai. Les resultats sur l’utilisation de la somatostatine sont contradictoires. Les resultats benefiques lorsque le critere de jugement de fistule est biologique n’ont pas ete confirmes par quatre essais sur cinq lorsque le critere de fistule etait clinique et/ou radiologique. Enfin, l’occlusion des canaux pancreatiques par de la fibrine ou l’utilisation de colle sur la surface de l’anastomose pancreatico-digestive n’ont pas diminue le risque de fistule. En conclusion, la duodeno-pancreatectomie cephalique decrite par Whipple reste la technique de reference d’exerese des cancers de la tete du pancreas. L’essai montrant l’interet de l’intubation du pancreas dans le jejunum merite d’etre confirme. En l’absence de resultats convergents, la somatostatine ou le drainage externe du canal de Wirsung peuvent etre reserves aux cas pour lesquels l’anastomose pancreatique semble precaire. Enfin, il a ete suggere par plusieurs etudes que l’experience des equipes semblait le meilleur moyen, non seulement de diminuer la morbidite et la mortalite peri-operatoires, mais aussi d’augmenter les chances de survie des malades.

Liver resection of transplantation for hepatocellular carcinoma?: Restrospective analysis of 215 patients with cirrhosis

BACKGROUND/AIMS Currently, surgical treatment of hepatocellular carcinoma in patients with cirrhosis is not clearly defined. The objective of this study was, in patients with cirrhosis with hepatocellular carcinoma, to compare liver resection to transplantation assessed by patient survival and to determine whether the tumor recurrence might be influenced by prognostic factors. METHODS We have gathered all the available data from six French Medical Universities, for 215 patients with cirrhosis with hepatocellular carcinoma surgically treated either by liver resection (102) or by transplantation (113). RESULTS The overall 5-year survival rate was similar in the transplantation group and in the resection group (32% vs. 31%, p=0.7). However, the 5-year survival rate without recurrence was higher in the transplantation group than in the resection group (60% vs. 14%, p<0.001). Three independent prognostic factors influenced significantly the survival without recurrence: the surgical treatment by transplantation (p<0.001), the number of tumors (p<0.01) and the tumor size (p<0.001). With these factors we defined a prognostic index (Ip) which allowed assessment of the probability of survival without recurrence: Ip= (Xie. x 1.41)+(Nbr T. x 0.19)+(Size TV. x 0.16); Xie=surgical treatment (Xie=0 if transplantation, Xie=1 if resection), Nbr.T. and Size TV.=number of tumors and size of the most voluminous tumor, respectively, according to the histologic study. CONCLUSIONS These results and this prognostic index are encouraging for liver transplantation as treatment of hepatocellular carcinoma in selected patients with cirrhosis.

Liver Transplantation for Neuroendocrine Tumors in Europe—Results and Trends in Patient Selection A 213-Case European Liver Transplant Registry Study

Objective:The purpose of this study was to assess outcomes and indications in a large cohort of patients who underwent liver transplantation (LT) for liver metastases (LM) from neuroendocrine tumors (NET) over a 27-year period. Background:LT for NET remains controversial due to the absence of clear selection criteria and the scarcity and heterogeneity of reported cases. Methods:This retrospective multicentric study included 213 patients who underwent LT for NET performed in 35 centers in 11 European countries between 1982 and 2009. One hundred seven patients underwent transplantation before 2000 and 106 after 2000. Mean age at the time of LT was 46 years. Half of the patients presented hormone secretion and 55% had hepatomegaly. Before LT, 83% of patients had undergone surgical treatment of the primary tumor and/or LM and 76% had received chemotherapy. The median interval between diagnosis of LM and LT was 25 months (range, 1–149 months). In addition to LT, 24 patients underwent major resection procedures and 30 patients underwent minor resection procedures. Results:Three-month postoperative mortality was 10%. At 5 years after LT, overall survival (OS) was 52% and disease-free survival was 30%. At 5 years from diagnosis of LM, OS was 73%. Multivariate analysis identified 3 predictors of poor outcome, that is, major resection in addition to LT, poor tumor differentiation, and hepatomegaly. Since 2000, 5-year OS has increased to 59% in relation with fewer patients presenting poor prognostic factors. Multivariate analysis of the 106 cases treated since 2000 identified the following predictors of poor outcome: hepatomegaly, age more than 45 years, and any amount of resection concurrent with LT. Conclusions:LT is an effective treatment of unresectable LM from NET. Patient selection based on the aforementioned predictors can achieve a 5-year OS between 60% and 80%. However, use of overly restrictive criteria may deny LT to some patients who could benefit. Optimal timing for LT in patients with stable versus progressive disease remains unclear.

A novel pregnane X receptor and S14‐mediated lipogenic pathway in human hepatocyte

The pregnane X receptor (PXR) initially isolated as a nuclear receptor regulating xenobiotic and drug metabolism and elimination, seems to play an endobiotic role by affecting lipid homeostasis. In mice, PXR affects lipid homeostasis and increases hepatic deposit of triglycerides. In this study, we show that, in human hepatocyte, PXR activation induces an increase of de novo lipogenesis through the up‐regulation of S14. S14 was first identified as a thyroid‐responsive gene and is known to transduce hormone‐related and nutrient‐related signals to genes involved in lipogenesis through a molecular mechanism not yet elucidated. We demonstrate that S14 is a novel transcriptional target of PXR. In addition, we report an increase of fatty acid synthase (FASN) and adenosine triphosphate citrate lyase genes expression after PXR activation in human hepatocyte, leading to an increase of fatty acids accumulation and de novo lipogenesis. RNA interference of the expression of S14 proportionally decreases the FASN induction, whereas S14 overexpression in human hepatic cells provokes an increase of fatty acids accumulation and lipogenesis. These results demonstrate for the first time that xenobiotic or drug‐activated PXR promote aberrant hepatic de novo lipogenesis via activation of the nonclassical S14 pathway. In addition, these data suggest that the up‐regulation of S14 by PXR may promote aberrant hepatic lipogenesis and hepatic steatosis in human hepatocytes. (HEPATOLOGY 2009.)

Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in maintenance liver transplant patients.

Although large retrospective studies have identified the presence of donor‐specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long‐term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixty‐seven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single‐antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min–max: 6–220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min–max: 2–45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28–11.05, p = 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody‐mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.

Long-term clinical and imaging follow-up of nonoperated branch duct form of intraductal papillary mucinous neoplasms of the pancreas.

Objectives The aim of our study was to perform a 10-year imaging and clinical prospective follow-up of patients with nonoperated branch duct (BD) intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Methods Forty-nine patients with BD-IPMN who displayed a low probability for malignancy were followed up including a clinical component and a series of imaging techniques such as computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography. Results After a mean follow-up period of 77 months, 77.5% of patients remained free of symptoms. An increase in the size and number of BD cysts without mural nodules and with no significant increase of main duct size occurred in 18 patients at an average interval of 47 months. Five patients were operated on owing to recurrent pancreatitis and/or an increase in the size of either cysts or the main duct (mean time delay after diagnosis: 20 months). Pathologically, they were diagnosed as benign adenoma (n = 1) or borderline (n = 4). Conclusions Our long-term clinical and imaging follow-up indicated that none of the patients with BD-IPMNs developed malignancy. Therefore, BD-IPMNs with no signs of malignancy should be managed conservatively. We propose that following a 2-year patient follow-up, biannual imaging follow-ups could be sufficient. Abbreviations IPMN - intraductal papillary mucinous neoplasm of the pancreas, BD - branch duct, MPD - main pancreatic duct, EUS - endoscopic ultrasound, CT scan - computed tomographic examination, MRCP - magnetic resonance cholangiopancreatography

Blood salvage autotransfusion during transplantation for hepatocarcinoma : does it increase the risk of neoplastic recurrence?

Impact of intraoperative blood salvage autotransfusion (IBSA) on neoplastic recurrence. during liver transplantations for hepatocellular carcinoma (LT‐HCC). Between January 1989 and February 2003, 16 patients received a LT‐HCC without IBSA. This group was compared with 31 patients who received the same surgical procedure during the same period, but with IBSA. Data were prospectively collected. All patients had at least a 1‐year postoperative follow up. Pairing was made according to the size of the largest nodule. The percentage of recurrence observed in the two groups was similar: 6.4% in the IBSA group vs. 6.3% in the group without IBSA. The median amount of transfused salvage blood was 1558 ml. The differences observed between the two groups concerned the Child score which was A in 58% patients of the IBSA group vs. 80% in the other group; the percentage of severe portal hypertension was 55% in the IBSA group vs. 31%; the median number of packed red blood cell units transfused intraoperatively was 7 in the IBSA group vs. 0, and the median number of frozen fresh plasma units transfused intraoperatively was 11 in the IBSA group vs. 4.5. It appears that IBSA, essentially used during the most haemorrhagic transplantations, could be used in the case of HCC because it does not modify the risk of neoplastic recurrence.

Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas

Aims:  The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN).

De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

The incidence and consequences of de novo donor‐specific anti‐HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver‐transplant patients, without preformed anti‐HLA DSAs, were tested for anti‐HLA antibodies, with single‐antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver‐enzyme levels until the last follow‐up, that is, 34 (1.5–77) months. Twenty‐one patients (14%) developed de novo DSAs. Of these, five patients had C1q‐binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody‐mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B‐cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient‐ and graft‐survival rates did not differ between patients with and without DSAs. In conclusion, liver‐transplant patients with liver abnormalities should be screened for DSAs and AMR.

Predictive Factors for Chronic Renal Failure One Year after Orthotopic Liver Transplantation

Chronic renal failure (CRF) is increasingly prevalent in solid-organ-transplant patients. This is in part related to the long-term use of calcineurin inhibitor (CNI) agents. However, in orthotopic liver-transplant (OLT) patients, the effects of superimposed hepatitis C virus (HCV)-related renal lesions could also be a factor. The aim of this cohort study (February 2000 to September, 2003) was to identify the predictive factors at one year post-transplantation for CRF in OLT patients associated with induction therapies. CRF was defined as having a creatinine clearance (CC) lower than 60 mL/min. Of the 97 transplants performed during that period, 72 were still functioning after one year. Of these, 33 patients (45.8%) had CRF. In univariate analysis, the predicting factors for CRF were recipient sex (female), initial liver disease (HCV-related cirrhosis), pre-transplant CC (<80 mL/mn), and post-transplant serum creatinine >130 μmol/L at day 3 and months (M) 1, 3, and 6. In multivariate analysis, the independent predictive factors for CRF included female sex [OR: 11.5 (2.3–58.3); p = 0.003], HCV infection [OR: 5.01 (1.1–22.7); p = 0.03], pre-OLT CC <80 mL/mn [OR: 5.4 (1.2–23.7); p = 0.025], and serum creatinine at M6 greater than 130 μmol/L [OR: 19.6 (3.7–102.5); p = 0.0004]. Among all of the predictive factors for post-OLT CRF, only one is modifiable: post-transplant serum creatinine, which could be, to some extent, related to the long-term use of CNIs.