Olivier Soubrane

Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka.

OBJECTIVE This review aims to assess the impact of implementing dedicated emergency surgical services, in particular acute care surgery, on clinical outcomes. BACKGROUND The optimal model for delivering high-quality emergency surgical care remains unknown. Acute Care Surgery (ACS) is a health care model combining emergency general surgery, trauma, and critical care. It has been adopted across the United States in the management of surgical emergencies. METHOD A systematic review was performed after PRISMA recommendations using the MEDLINE, Embase, and Psych-Info databases. Studies assessing different care models and institutional factors affecting the delivery of emergency general surgery were included. RESULTS Twenty-seven studies comprising 744,238 patients were included in this review. In studies comparing ACS with traditional practice, mortality and morbidity were improved. Moreover, time to senior review, delays to operating theater, and financial expenditure were often reduced. The elements of ACS models varied but included senior clinicians present onsite during office hours and dedicated to emergency care while on-call. Referrals were made to specialist centers with primary surgical assessments taking place on surgical admissions units rather than in the emergency department. Twenty-four-hour access to dedicated emergency operating rooms was also described. CONCLUSIONS ACS models as well as centralized units and hospitals with dedicated emergency operating rooms, access to radiology and intensive care facilities (ITU) are all factors associated with improved clinical and financial outcomes in the delivery of emergency general surgery. There is, however, no consensus on the elements that constitute an ideal ACS model and how it can be implemented into current surgical practice.

Randomized Trial of Choledochocholedochostomy With or Without a T Tube in Orthotopic Liver Transplantation

ObjectiveTo compare the incidence of biliary complications after liver transplantation in patients undergoing choledochocholedochostomy reconstruction with or without T tube in a multicenter, prospective, randomized trial. Summary Background DataSeveral reports have suggested that biliary anastomosis without a T tube is a safe method of biliary reconstruction that could avoid complications related to the use of T tubes. No large prospective randomized trial has so far been published to compare the two techniques. MethodsOne hundred eighty recipients of orthotopic liver transplantation were randomly assigned to choledochocholedochostomy with (n = 90) or without (n = 90) a T tube in six French liver transplantation centers. All types of biliary complications were taken into account. ResultsThe overall biliary complication rate was increased in the T-tube group, even though these complications did not lead to an increase in surgical or radiologic therapeutic procedures. The major significant complication was cholangitis in the T-tube group; this did not occur in the other group. The incidence of biliary fistula was 10% in the T-tube group and 2.2% in the group without a T tube. Other biliary complications were similar. The complication rate of cholangiography performed with the T tube was greater than with other types of biliary exploration. The graft and patient survival rates were similar in the two groups. ConclusionThis study is the first large prospective, randomized trial of biliary complications with or without a T tube. The authors found an increase in the biliary complication rate in the T-tube group, which was linked to minor complications. The T tube did not provide a safer access to the biliary tree compared with the others types of biliary explorations. The authors recommend the performance of choledochocholedochostomy without a T tube in liver transplantation.

Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis

Rubbia‐Brandt L, Lauwers G Y, Wang H, Majno P E, Tanabe K, Zhu A X, Brezault C, Soubrane O, Abdalla E K, Vauthey J‐N, Mentha G & Terris B
(2010) Histopathology56, 430–439
Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin‐associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis

Early survival and safety of ALPPS: first report of the International ALPPS Registry.

Objectives:To assess safety and outcomes of the novel 2-stage hepatectomy, Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS), using an international registry. Background:ALPPS induces accelerated growth of small future liver remnants (FLR) to allow curative resection of liver tumors. There is concern about safety based on reports of higher morbidity and mortality. Methods:A Web-based data entry system was created with password access and data pseudoencryption (NCT01924741). All patients with complete 90-day data were included. Multivariate logistic regression analysis was performed to identify independent risk factors for severe complications and mortality and volume growth of the FLR. Results:Complete data were available for 202 patients. A total of 141 (70%) patients had colorectal liver metastases (CRLM). Median starting standardized future liver remnants of 21% increased by 80% within a median of 7 days. Ninety-day mortality was 19/202 (9%). Severe complications including mortalities (Clavien-Dindo ≥IIIb) occurred in 27% of patients. Independent factors for severe complications were red blood cell transfusion [odds ratio (OR), 5.2), ALPPS stage I operating time greater than 300 minutes (OR, 4.4), age more than 60 years (OR, 3.8), and non-CRLM (OR, 2.7). Age, use of Pringle maneuver, and histologic changes led to less volume growth. In patients younger than 60 years with CRLM, 90-day mortality was similar to conventional 2-stage hepatectomies for CRLM. Conclusions:This is the first analysis of the ALPPS registry showing that ALPPS has increased perioperative morbidity and mortality in older patients but better outcomes in patients with CRLM.

Selective repopulation of normal mouse liver by Fas/CD95-resistant hepatocytes

Hepatocyte transplantation might represent a potential therapeutic alternative to liver transplantation in the future; however, transplanted cells have a limited capacity to repopulate the liver, as they do not proliferate under normal conditions. Recently, studies in urokinase (uPA) transgenic mice and in fumarylacetoacetate hydrolase (FAH)-deficient mice have shown that the liver can be repopulated by genetically engineered hepatocytes harboring a selective advantage over resident hepatocytes. We have reported that transgenic mice expressing human Bcl-2 in their hepatocytes are protected from Fas/CD95-mediated liver apoptosis. We now show that Bcl-2 transplanted hepatocytes selectively repopulate the liver of mice treated with nonlethal doses of the anti-Fas antibody Jo2. FK 506 immunosuppressed mice were transplanted by splenic injection with Bcl-2 hepatocytes. The livers of female recipients were repopulated by male Bcl-2 transgenic hepatocytes, as much as 16%, after 8 to 12 administrations of Jo2. This only occurred after anti-Fas treatment, confirming that resistance to Fas-induced apoptosis constituted the selective advantage of these transplanted hepatocytes. Thus, we have demonstrated a method for increasing genetic reconstitution of the liver through selective repopulation with modified transgenic hepatocytes, which will allow optimization of cell and gene therapy in the liver.

Metastatic endocrine tumors: medical treatment, surgical resection, or liver transplantation.

Abstract. We reviewed our experience with 34 patients with metastatic endocrine tumors (METs) who were treated by different modalities. Eight patients were treated by chemotherapy or chemoembolization because of stable disease or surgical contraindications. Seventeen patients underwent curative or cytoreductive surgical resection. Nine patients received grafts based on the following criteria: no extrahepatic spread on imaging workup and nonresectable symptomatic metastatic disease. Of the eight medically treated patients, the five patients with initial stable clinical condition are alive 32 to 56 months after referral. Of the 17 patients treated by liver resection, 13 are alive 6 to 108 months after surgery, and 7 are disease-free. After curative resection, the 5-year actuarial survival and disease-free survival rates were 62% and 52%, respectively. Of the nine grafted patients, three patients grafted for carcinoid tumor are alive at 15, 24, and 62 months, one of whom has a late recurrence. Our results indicate that therapeutic indications for METs should be based on age, clinical symptoms, histologic type, and tumor extension: Patients with stable MET may benefit from surgical restraint; liver resection in patients with aggressive MET may provide good long-term palliation and possibly cure one-third of the patients; liver transplantation should be restricted to young patients with nonresectable carcinoid MET but remains a high-risk operation because of previous surgery and chemoembolization.

Laparoscopic Left Lateral Sectionectomy in Living Donors: Safety and Reproducibility of the Technique in a Single Center

Background Data and Objective:Left lateral sectionectomy for liver transplantation in children performed through laparoscopy is an innovative procedure that was developed by considering our acquired experience in both laparoscopic liver resection and graft harvesting in living donors. The main goal was to minimize donor morbidity while preserving the abdominal wall. Herein, we report the technical feasibility and reproducibility, and compared it with open liver resection (OLR). Methods:Sixteen successive donors underwent a laparoscopic liver resection (LLR) from 2001 to 2005. They were compared with 14 other donors who underwent a standard open liver resection (OLR) during a first period (1998–2004). First, this report describes the technical features of laparoscopic resection. Second, perioperative morbidity and graft characteristics were compared according to the use or not of the laparoscopic approach. Results:Laparoscopic harvesting was successfully performed in 15 of 16 cases in an intention-to-treat basis. One conversion was required to ensure the quality of the laparoscopic repair of a left portal vein injury occurring during the pedicle dissection. No specific complication related to laparoscopy was observed. As compared with OLR, the operation was longer (320 ± 67 vs. 244 ± 55 minutes, P < 0.005). The blood loss was significantly lower in the LLR group (18.7 ± 44.2 vs. 199.2 ± 185.4 mL, P < 0.005). The morbidity rate was similar in both groups (18.7% in LLR vs. 35.7% in OLR). One donor in the LLR group experienced a bile leak treated by redo laparoscopy. Grafts were anatomically similar irrespective of the use of laparoscopy. The duration of hospital stay and use of self-infused morphine pump was not different between the 2 groups. Conclusion:Left lateral section harvesting by laparoscopy is a safe and reproducible procedure, allowing to obtain similar grafts as compared with laparotomy and can therefore be recommended to transplant centers that have previous experience in laparoscopic liver resection.

Liver transplantation for hepatopulmonary syndrome: a ten-year experience in Paris, France.

Background. Although the possibility of reversing hepatopulmonary syndrome (HPS) after liver transplantation is now well established, the proportion of patients in whom reversibility is observed and the time to resolution of HPS remain uncertain. Methods. We analyzed the outcome of all adult patients with HPS who underwent orthotopic liver transplantation in all the liver transplant centers in Paris, during a 10-year period. Results. Twenty-three adult patients (median age, 47 years; range, 14–64) underwent transplantation in four institutions. Median PaO2 was 52 (range, 32–67) mm Hg and median alveolar-arterial oxygen gradient was 66 mm Hg. When patients were breathing 100% O2, median PaO2 was 310 (range, 74–663) mm Hg. Median isotopic shunt ratio was 33% (range, 0–80%). The overall mortality during the study period was 30.5% (7/23). Perioperative mortality was 8.5%, whereas late mortality was 22%. None of the preoperative characteristics of HPS (isotopic shunt ratio, PaO2 on room air or on 100% oxygen) was associated with overall postoperative mortality. Of the 21 patients surviving the perioperative period (median follow-up, 17 months; range, 0.5–72), a decrease in alveolar-arterial oxygen gradient of at least 5 mm Hg and at least 10 mm Hg was observed in 21 of 21 and in 18 of 21 patients, respectively, with great variations in the time of improvement. The threshold of 70 mm Hg was reached in 15 patients. The lower the preoperative PaO2, the longer the time to reach this point. Conclusion. Our data strongly support the role of orthotopic liver transplantation in adult patients with HPS, regardless of its severity.

Predictors of Long-Term Survival After Liver Transplantation for Metastatic Endocrine Tumors: An 85-Case French Multicentric Report

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver ≥120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven.

Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis

Nonalcoholic fatty liver disease, frequently associated with obesity, can lead to nonalcoholic steatohepatitis (NASH) and cirrhosis. The pathophysiology of NASH is poorly understood, and no effective treatment is available. In view of a potential deleterious role for reactive oxygen species (ROS), we investigated the origin of ROS overproduction in NASH. Mitochondrial production of ROS and its alterations in the presence of antioxidant molecules were studied in livers from ob/ob mice that bear a mutation of the leptin gene and develop experimental NASH. N‐acetyl‐cysteine and the superoxide dismutase (SOD) mimics ambroxol, manganese [III] tetrakis (5,10,15,20 benzoic acid) (MnTBAP), and copper [II] diisopropyl salicylate (CuDIPS) were used to target different checkpoints of the oxidative cascade to determine the pathways involved in ROS production. Liver mitochondria from ob/ob mice generated more O2°− than those of lean littermates (P < .01). Ex vivo, all three SOD mimics decreased O2°− generation (P < .001) and totally inhibited lipid peroxidation (P < .001) versus untreated ob/ob mice. Those modifications were associated with in vivo improvements: MnTBAP and CuDIPS reduced weight (P < .02) and limited the extension of histological liver steatosis by 30% and 52%, respectively, versus untreated ob/ob mice. In conclusion, these data demonstrate deleterious effects of superoxide anions in NASH and point at the potential interest of nonpeptidyl mimics of SOD in the treatment of NASH in humans. (HEPATOLOGY 2004;39:1277–1285.)