Safety and outcome of combined liver and pancreatic resections.

BACKGROUND: In Western countries, combined liver and pancreatic resections (CLPR) are performed rarely because of the perceived high morbidity and mortality rates. This study evaluated the safety and outcomes of CLPR at a tertiary European centre for hepatopancreatobiliary surgery. METHODS: A review of two prospectively maintained databases for pancreatic and liver resections was undertaken to identify patients undergoing CLPR between January 1994 and January 2012. Clinicopathological and surgical outcomes were analysed. Univariable and multivariable analyses for postoperative morbidity were performed. RESULTS: Fifty consecutive patients with a median age of 58 (range 20-81) years underwent CLPR. Indications for surgery were neuroendocrine carcinoma (16 patients), biliary cancer (15), colonic cancer (5), duodenal cancer (1) and others (13). The type of pancreatic resection included pancreaticoduodenectomy (30), distal pancreatectomy (17), spleen-preserving distal pancreatectomy (2) and total pancreatectomy (1). Twenty-three patients had associated major hepatectomies, 27 underwent minor liver resections and 11 had associated vascular resections. Mortality and morbidity rates were 4 and 46 per cent respectively. Univariable and multivariable analysis showed no differences in postoperative morbidity in relation to extent of liver resection or type of pancreatic resection. Use of preoperative chemotherapy was the only independent risk factor associated with postoperative morbidity (P = 0.021). CONCLUSION: CLPR can be performed with fairly low morbidity and mortality rates. Postoperative outcomes were not affected by the extent of liver resection or the type of pancreatic resection. Patients receiving chemotherapy should be evaluated carefully before surgery is considered.

Two-stage hepatectomy for multiple bilobar colorectal liver metastases.

BACKGROUND: As surgical resection of colorectal liver metastases (CLM) remains the only treatment for cure, efforts to extend the surgical indications to include patients with multiple bilobar CLM have been made. This study evaluated the long-term outcome, safety and efficacy of two-stage hepatectomy (TSH) for CLM in a large cohort of patients. METHODS: Patients undergoing surgery between December 1996 and December 2009 were reviewed. The early postoperative and long-term outcomes as well as the patterns of failure to complete TSH and its clinical implications were analysed. RESULTS: Eighty patients were scheduled to undergo TSH. Sixty-one patients had completion of TSH combined with (58 patients), or without (3) portal vein embolization/ligation (PVE/PVL). Five patients were excluded after first-stage hepatectomy and 14 after PVE/PVL. The 5-year overall survival rate and median survival in patients who completed TSH were 32 per cent and 39·6 months respectively, and corresponding recurrence-free values were 11 per cent and 9·4 months respectively. Six patients were alive beyond 5 years after TSH. Multivariable logistic regression analysis showed that failure to complete TSH was driven by two independent prognostic scenarios: three or more CLM in the future remnant liver (FRL) combined with age over 70 years predicted tumour progression after first-stage hepatectomy, and three or more CLM in the FRL combined with carcinomatosis at the time of first-stage hepatectomy predicted the development of additional FRL metastases after PVE/PVL. CONCLUSION: A therapeutic strategy using TSH provided acceptable long-term survival with no postoperative mortality. Further efforts are needed to increase the number of patients who undergo TSH successfully.

Consequences of chemotherapy on resection of colorectal liver metastases.

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.

Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: preliminary results of a case-control study.

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.

Liver transplantation in recipients over 65 yr old: a single center experience.

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.

Preliminary experience with the hanging maneuver for pancreaticoduodenectomy.

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 intraoperative 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.

Patient preparation before surgery for cholangiocarcinoma.

AIM: Multiorgan dysfunction is often encountered in jaundiced patients and may compromise the postoperative outcome after liver resection for cholangiocarcinoma (CCA). The aim of the present study was to elucidate evidence-based medicine regarding the benefit of the available preoperative treatments currently used for the preparation of patients before surgery for hilar CCA. MATERIAL AND METHODS: An electronic search using the Medline database was performed to identify relevant articles relating to renal dysfunction, bacterial translocation, hemostasis impairment, malnutrition, liver failure, and postoperative outcome in jaundiced patients undergoing liver resection for CCA. RESULTS: There is grade B evidence to expand the extracellular water volume and to administer oral synbiotic supplements. Intravenous vitamin K administration is an effective treatment. Perioperative nutritional support should be administered preferably by the enteral route in severely malnourished patients with compromised liver function undergoing extended liver resection (grade A evidence). There is only grade C evidence to recommend a portal vein embolization in patients with CCA when the future remnant liver volume is <40%. CONCLUSIONS: A simplified scheme that might be useful in the management of patients presenting with obstructive jaundice was presented. Despite surgical technique improvements, preparation of patients for surgery will continue to be one of the major determinants for the postoperative prognosis of jaundiced patients.

Twenty seven years of experience in pediatric liver transplantation in Strasbourg: focus on the ex situ split techniques.

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.

[Pancreaticoduodenectomy for cancer of the head of the pancreas]. / Duodénopancréatectomie céphalique pour cancer.

Many modifications of the original technique have been proposed to try to improve the results of the pancreaticoduodenectomy described by Whipple. To evaluate these modifications, we have reviewed randomized controlled trials, meta-analyses, and well-conducted retrospective series. Neither total pancreatectomy nor extended lymph node dissections have shown an improve of survival in retrospective studies. Preoperative evidence of mesenteric or portal vein involvement does not contraindicate pancreatic resection and survival rates are similar to those of patients with no venous involvement. Prospective trials and one meta-analysis have shown neither advantage nor disadvantage of pylorus-preserving pancreaticoduodenectomy or of pancreatico-gastric anastomosis. Three trials and one meta-analysis of pancreatico-gastric anastomosis have failed to demonstrate a decrease in the risk of pancreatic fistula. Two trials suggest that the risk of fistula formation is decreased by implantation of the pancreatic remnant into the jejunum or by trans-jejunal stenting of the pancreatico-jejunal anastomosis with external drainage; but these findings are not supported by a third trial. The results of the antisecretory use of somatostatin are contradictory. Leak and fistula formation were decreased when the criteria for leakage was based on laboratory findings; but in 4 out of 5 trials, somatostatin did not decrease the incidence of clinical fistula. The use of fibrin glue to occlude the pancreatic duct or seal the cut surface of the pancreas did not decrease the rate of intra-abdominal complications. In conclusion, the pancreaticoduodenal resection described by Whipple may still be considered the gold standard for resection of pancreatic cancer. The technical experience of surgeons and their institutional support staff resulted in lower perioperative morbidity and mortality and in higher survival rates.

Minimally invasive and selective hydrodynamic gene therapy of liver segments in the pig and human.

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.

[Recurrence of hepatitis C virus (HCV) infection after liver transplantation for HCV-related disease: host factors and viral factors implicated in the occurrence and the severity of HCV recurrence]. / Récurrence de l'infection par le virus de l'hépatite C (VHC) après transplantation du foie pour hépatopathie due au VHC: facteurs liés à l'hôte et facteurs viraux impliqués dans la survenue et la gravité de la récurrence de l'hépatite virale C.

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.

[Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients with solid organ transplantation: a clinical, neurophysiological and neuropathological study of 4 cases]. / Polyradiculonévrite chronique chez des patients avec une greffe d'organe solide: une étude clinique, neurophysiologique et neuropathologique de 4 cas.

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.

Comparison of clearance predictions using primary cultures and suspensions of human hepatocytes.

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.

[Technique of surgical ampullectomy]. / Technique de l'ampullectomie chirurgicale.

We describe the technique of surgical ampullectomy, which consists of complete resection of the papilla of Vater, including the sphincter, the distal part of common bile duct and Wirsung duct, and the duodenal wall around the papilla. Limits of resection are assessed by frozen section, particularly on both biliary and pancreatic ducts which are sutured together and reinserted on the duodenal wall. Surgical ampullectomy, combined with frozen section, is associated with a low morbidity, and represents a valid alternative to pancreaticoduodenectomy and endoscopic ampullectomy for presumed-benign ampullomas.

Simultaneous resection of colorectal primary tumour and synchronous liver metastases.

BACKGROUND: The surgical strategy for treatment of synchronous colorectal liver metastases remains controversial. The outcome and overall survival of patients presenting with such metastases, treated either by simultaneous resection or by delayed resection, were evaluated. METHODS: From 1987 to 2000, 97 patients presented with synchronous colorectal liver metastases, of whom 35 (36 per cent) underwent a simultaneous resection and 62 patients (64 per cent) a delayed resection. Simultaneous resection was considered prospectively for patients with fewer than four unilobar metastases. RESULTS: Age, blood transfusion requirements, operating time, duration of inflow occlusion, hospital stay and mortality rate were similar in the two groups. The morbidity rate did not differ significantly (23 per cent after simultaneous resection and 32 per cent after delayed resection). The location of the primary tumour and extent of liver resection did not influence the morbidity rate significantly in the simultaneous resection group. The overall survival rate was 94, 45 and 21 per cent at 1, 3 and 5 years respectively after simultaneous resection, and 92, 45 and 22 per cent after delayed resection. CONCLUSION: In selected patients, simultaneous resection of the colorectal primary tumour and liver metastases does not increase mortality or morbidity rates compared with delayed resection, even if a left colectomy and/or a major hepatectomy are required.

[Pheochromocytoma in internal medicine: distinctive features and place of 123I MIBG scintigraphy]. / Le phéochromocytome en médecine interne: particularités et place de la scintigraphie à la MIBG 123.

PURPOSE: Pheochromocytoma diagnosis uses the localization of the tumour, particularly thanks to MIBG scintigraphy. The aims of this study were to evaluate the sensibility and specificity of this exam, his opportunity towards clinical and biological profile of patients with pheochromocytoma suspicion in Internal Medicine and towards others techniques of imaging. We tried to define the most effective and least expensive approach of pheochromocytoma diagnosis. METHOD: This study was carried out over 15 years period on 80 patients in Internal Medicine who underwent 123I MIBG scintigraphy for pheochromocytoma suspicion. RESULTS: Among the 80 patients who underwent 123I MIBG scintigraphy, only 18 suffered from a pheochromocytoma. A very few symptoms were specific, like the triad "headaches, sweating, palpitations" whose onlyone third of patients was concerned by. The diagnosis approach carried on with urine catecholamine measurement, who was specific when metanephrines were increased whatever their levels and when normetanephrines were higher or equal than 1,5 time the norme. Then, abdominal CT or MRI scanning and 123I MIBG scintigraphy were performed for localization of the tumor. The sensibility of scintigraphy was 83%, its specificity was 89%. That is comparable with other studies about 131I MIBG. CONCLUSION: Prescription of MIBG scintigraphy in Internal Medicine appears to be excessive: 77,5% of patients don't have a pheochromocytoma. It is related to the lack of specific symptoms, the wrong positives in urine normetanephrines measurement and the discovery of incidentaloms by CT scanning. The scintigraphy should be used like a topographic and not a diagnosis exam.

Hepatocyte ploidy in regenerating livers after partial hepatectomy, drug-induced necrosis, and cirrhosis.

The hepatocyte ploidy was investigated by flow cytometry in regenerating Sprague-Dawley rat livers following either drug-induced acute necrosis (single sublethal doses of D-galactosamine or thioacetamide) or drug-induced chronic cirrhosis (repeated thioacetamide injections for 10-18 weeks) and in regenerating livers following 70% partial hepatectomy and was compared with that of normal hepatocytes. Twenty-four hours after partial hepatectomy, a significant decrease in 2n (1 diploid nucleus) hepatocytes and a significant increase in 8n (1 octoploid nucleus) hepatocytes occurred. In contrast, 24 h following induction of acute hepatic failure by single D-galactosamine or thioacetamide injections, a significant increase in 2n hepatocytes was observed, whereas the proportion of 8n hepatocytes remained unchanged. The liver ploidy returned to basal values within 21 days in all cases. In cirrhotic livers induced by chronic thioacetamide injections, the rate of 2n hepatocytes was about ten times that of the controls having the same age, while 4n (1 tetraploid nucleus) and 8n hepatocytes were one third of controls. The binucleation rate was also significantly decreased.