Transplantation of genetically modified hepatocytes after liver preconditioning in Watanabe heritable hyperlipidemic rabbit.

BACKGROUND: Hepatocyte transplantation is a potentially less invasive alternative to liver transplantation for treating inherited metabolic liver diseases. We developed an autotransplantation protocol of ex vivo genetically modified hepatocytes combining lentiviral transduction and transplantation after liver preconditioning by partial portal vein embolization. We investigated the metabolic efficiency of this approach in Watanabe rabbits, animal model of familial hypercholesterolemia. METHODS: Our autotransplantation experimental protocol was used in two groups of rabbits (n = 10), experimental and sham, receiving transduced and control hepatocytes, respectively. Isolated hepatocytes from left liver lobes were transduced using recombinant lentiviruses. Median lobe portal branches were embolized under fluoroscopic control. Functional measurement of low-density lipoprotein (LDL) receptor expression was assessed by LDL internalization assays. Cholesterol level evolution was monitored. Rabbits were killed 20 wk after the procedure. RESULTS: Three rabbits of each group died several hours after hepatocyte transplantation; autopsy revealed portal vein thrombosis in two rabbits from each group. The protocol was therefore modified with hepatocytes being transplanted through splenic injection. Lentiviral hepatocyte transduction efficacy was 64.5%. Fluorescence microscopy revealed Dil-LDL internalization of transduced hepatocytes. Seven rabbits in each group were considered for lipid analysis. Four weeks after autotransplantation, median total cholesterol level decreased in the experimental group, without reaching statistical significance (8.9 [8.0-9.8] g/L versus 6.3 [0.5-8.3]; P = 0.171). In the experimental group, enzyme-linked immunosorbent assay detected significant antibody expression against human low-density lipoprotein receptor. CONCLUSIONS: Autotransplantation protocol allowed a nonstatistically significant improvement of the lipid profile in Watanabe rabbits. Further experiments involving a larger number of animals are necessary to confirm or refute our findings.

Africa Guidelines for Hepatocellular Carcinoma Buildup Process.

PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Synchronous pyogenic liver abscess and acute cholecystitis: how to recognize it and what to do (emergency cholecystostomy followed by delayed laparoscopic cholecystectomy).

BACKGROUND: The treatment of synchronous pyogenic liver abscess (PLA) and acute cholecystitis (AC) may be challenging. Moreover, because of the similarity of symptoms and the suboptimal accuracy of ultrasound (US), PLA(s) may be undetected, unless a computer tomography (CT) scan is performed. The aims of this study were (1) to evaluate the results of emergency cholecystostomy (CS) and late laparoscopic cholecystectomy (LC) in such a population and (2) to identify the criteria for selecting patients with AC and a high risk of having synchronous PLA(s) for referral for a CT scan. METHODS: A retrospective analysis of the outcome of 12 patients with AC and PLA(s) treated by emergency CS followed by delayed LC from January 1996 through May 2010 at a tertiary-care university hospital was performed. Clinical, laboratory, and radiological data of patients with synchronous AC and PLA(s) are compared with those of 66 patients with "simple" AC. RESULTS: The association of age >55 years, temperature >38°C, WBC count >12,000/ml, and ASAT >50 UI/l and/or ALAT >75 UI/l allows for the selection of patients at high risk of PLA to undergo a CT scan (sensitivity: 100%; specificity: 86%). All treated patients had a sudden improvement within 24 h following CS. PLA was treated in 10/12 patients (83%). Hospital stay lasted 21.5 ± 3.5 days. Ten patients underwent elective LC 12 ± 4 weeks after CS with no conversion and 30% perioperative morbidity. Operating time was 91 min. Hospital stay was 1.7 days [7 patients (70%) underwent surgery as an outpatient]. CONCLUSIONS: A simple algorithm is presented for the selection of patients with AC to undergo a CT scan to identify synchronous PLA. Emergency CS followed by delayed LC is a viable, first-line treatment option for synchronous PLA and AC.

Laparoscopic major hepatectomy can be safely performed with colorectal surgery for synchronous colorectal liver metastasis.

BACKGROUND: The optimal strategy for resectable synchronous colorectal liver metastases remains controversial. Although some authors advocate a staged treatment, an increasing number of studies have reported that combined colorectal and liver resection is safe. Laparoscopic combined resection in primary colorectal cancer with synchronous liver metastases has been reported but there are no specific data for major liver resections. In the present study, we evaluated the feasibility of a simultaneous entirely laparoscopic procedure, in the light of the benefits of laparoscopy in both colon and liver surgery, and discussed the benefits of this strategy. METHODS: Two cases are presented of totally laparoscopic major liver resections associated with laparoscopic colorectal resections for synchronous liver metastases with the emphasis on the technical aspects. Duration of surgery, blood loss and post-operative outcome were evaluated. RESULTS: Laparoscopic right hepatectomy or left hepatectomy with simultaneous colon resection for liver metastasis was feasible and safe with only one suprapubic 5-mm trocar added to the usual trocar sites. The mean duration of surgery was 327 min with a mean estimated blood loss of 200 ml. The post-operative course was uneventful. DISCUSSION: In selected patients, laparoscopic major hepatectomies for unilobular synchronous metastases can be safely performed simultaneously with colorectal surgery.

[Clinical, epidemiological and therapeutic features of biliary tract cancers: about 20 cases]. / Cancers biliaires: aspects épidémiologiques cliniques et thérapeutiques à propos de 20 cas.

Biliary tract cancers mainly occur in two sites: gallbladder cancer which are adenocarcinomas and intra- and extrahepatic cholangiocarcinomas. We conducted a retrospective study of 20 cases with biliary tract cancer in the Department of Surgery at the General Hospital in Grand-Yoff between January 2006 and October 2014. 40% of patients had gallbladder cancer, 60% of patients had common bile duct cancer. Sex ratio was 1. The average age of patients was 58.1 years. The average time to diagnosis was 3.77 months. Symptomatology was dominated by icteric syndrome and right hypochondrium pain. All patients had biological manifestation of cholestatic syndrome. Abdominal ultrasound was performed in 65% of patients, while abdominal CT scan in 85% of cases and MRI in 35% of cases. Advanced cancers were predominant in our case series (n=19). The majority of patients underwent palliative surgery. The most practiced treatment was biliary diversion (50% of patients). There was a predominance of cholangiocarcinomas. The overall operative morbidity rate was 43.75%. The overall mortality rate in our patients with biliary tract cancers of any site was 31.25%. Median survival was 4 months and a half. Biliary tract cancers have multifaceted features and can be differentiated essentially among intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder adenocarcinoma whose evolution is globally different but the prognosis is spontaneously poor.

[Acute generalized peritonitis due to uterine perforation following abortion: case study observation]. / Péritonite aigue généralisée par perforation utérine post abortum à propos d'une observation.

UNLABELLED: Clandestine abortion is known to be a major contributor to maternal mortality. We report a case of a 25-year old patient in her 12th week of amenorrhea with peritonitis due to uterine perforation following abortion, admitted with abdomen and pelvis pain, vomiting and diarrhea. Clinical examination on admission showed asthenic peritonitis. Surgical exploration showed widespread acute peritonitis secondary to a perforation of the uterine dome, with collection of 1500 cc of purulent material, dilated bowel loops and multiple false membranes. SURGERY: pus aspiration, peritoneal lavage; uterine suture, drainage. The postoperative course was uneventful, the patient was discharged after 15 days.

Laparoscopic liver resection for localized primary intrahepatic bile duct dilatation.

BACKGROUND: Primary intrahepatic bile duct dilatation (IHBD) may present as a localized form in which resection of the affected liver can prevent immediate and late complications. Laparoscopy has gained large interest in liver surgery. It also allows a safe and efficient exploration of the common bile duct. METHODS: We performed 10 laparoscopic liver resections for localized IHBD, on 7 women and 3 men (mean age 47 years). Resections were 2 right hepatectomies, 4 left hepatectomies, and 4 left lateral sectionectomies. Three patients had associated common bile duct stones that were treated through intraoperative cholangioscopy. RESULTS: The mean operative time was 303.9 minutes. The mean blood loss was 217 mL. None of these patients required hand assistance or conversion to open surgery. One patient suffered a residual collection that was drained percutaneously. The postoperative course was uneventful in the other patients. The mean hospital stay was 5.3 days. No recurrence of cholangitis was observed during the follow-up period. CONCLUSIONS: The laparoscopic treatment of IHBD is safe and should be performed by teams with expertise in both hepatobiliary surgery and laparoscopy.