Guillaume Pourcher

Volumetric Portal Embolization: A New Concept to Improve Liver Regeneration and Hepatocyte Engraftment.

Background Hepatocyte transplantation has been proposed as an alternative to orthotopic liver transplantation to treat metabolic liver diseases. This approach requires preconditioning of the host liver to enhance engraftment of transplanted hepatocytes. Different methods are currently used in preclinical models: partial hepatectomy, portal ligature or embolization, and radiotherapy or chemotherapeutic drugs. However, these methods carry high risks of complications and are problematic for use in clinical practice. Here, we developed an innovative method called volumetric (distal, partial, and random) portal embolization (VPE), which preserves total liver volume. Methods Embolization was performed in the portal trunk of C57BL6 adult mice with polyester microspheres, to ensure a bilateral and distal distribution. The repartition of microspheres was studied by angiographic and histological analyses. Liver regeneration was evaluated by Ki67 labeling. Optimal conditions for VPE were determined, and the resulting regeneration was compared with that after partial hepatectomy (70%). Labeled adult hepatocytes were then transplanted, and engraftment was compared between embolized (n = 19) and nonembolized mice (n = 8). Engraftment was assessed in vivo and histologically by tracking labeled cells at day 5. Results The best volumetric embolization conditions, which resulted in the regeneration of 5% of total liver, were 8 × 106 ten-micron microspheres infused with a 29 G needle directly into the portal trunk at 3.3 &mgr;L/s. In these conditions, transplanted hepatocytes engraftment was significantly higher than that in control conditions (3 vs 0.65%). Conclusions The VPE is a new, minimally invasive, and efficient technique to prepare the host liver for cell transplantation.

Bariatric surgery in HIV patients: experience of an Obesity Reference Center in France

BACKGROUND Few data on bariatric surgery are available regarding obese human immunodeficiency virus (HIV)-infected patients. SETTINGS Antoine Beclere hospital, Clamart, Paris-sud University, France METHODS: Prospective observational follow-up study recruited HIV-infected patients who underwent bariatric surgery from 2009 to 2015. Baseline demographic characteristics, surgery characteristics, perioperative outcomes, changes in weight loss, HIV markers, antiretroviral drug plasma levels are described. RESULTS There were 10 patients followed before and after sleeve gastrectomy: 2 men and 8 women; 50% of African origin; median age, 48.5 years, median time since HIV infection, 7.5 years; median body mass index, 48.5 kg/m2. Of patients, 8 had co-morbidities. All except 2 patients received antiretroviral drugs at the time of surgery with a median CD4 cell count at 709/mm3. There was no death or postoperative infectious complications. The median follow-up was 18 months (range, 15-55). The median postoperative weight loss was 43 kg (range, 17-83). Median percentage of excess weight loss was 82.5% (range, 35-119) at the latest visit after surgery. All co-morbidities were resolutive with weight loss. We observed no significant modification of CD4 cell count before and after surgery. Pharmacokinetics of antiretroviral drugs remains adequate and efficacious. CONCLUSION Our prospective series is the largest one on sleeve gastrectomy procedures performed on obese-treated HIV-infected patients. The sleeve generates good results in weight loss, with no significant impact on HIV infection, and with improvement of obesity-associated co-morbidities. Optimal management of HIV-infected patients with morbid obesity may include classical surgical procedures.

Single-port sleeve gastrectomy for super-obese patients

BACKGROUND Laparoscopic sleeve gastrectomy, which has become a primary bariatric procedure in super-obese patients (SOPs), is associated with considerable weight loss. Traditionally, laparoscopic sleeve gastrectomy requires 4-7 skin incisions. Single-port laparoscopic surgery is now feasible for bariatric surgery. OBJECTIVES To evaluate the feasibility and safety of single-port sleeve gastrectomy (SPSG) for SOPs. SETTING Department of Abdominal and Minimally Invasive Surgery, Antoine Beclere Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Sud University, France. METHODS Evaluation of the outcomes on patients who underwent surgery consecutively from June 2010 to June 2013 with follow-up of>1 year. RESULTS In total, 62 patients (46 women, 16 men) underwent SPSG. The median age was 41 years (range 19-67), median preoperative body mass index was 52.2 kg/m(2) (range 50-87), median operative time was 89 minutes (range 42-212). Twelve patients required additional trocars, and 4.8 % developed complications. The median postoperative stay was 4 days (range 3-9 days) and median follow-up period was 21 months (range 12-48 months) with no loss of follow-up. The median percentage of excess weight loss was 69.7% (range 52%-100%) and percentage of weight loss was 36% (28%-56%) for the same period. CONCLUSION SPSG for SOPs was found to be technically feasible, reproducible, and safe in this series.

The Transcription Factor 7-Like 2–Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Axis Connects Mitochondrial Biogenesis and Metabolic Shift with Stem Cell Commitment to Hepatic Differentiation

Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remains poorly characterized. Here, we identified a transcriptional regulatory axis, composed of transcription factor 7‐like 2 (TCF7L2) (a downstream effector of the Wnt/β‐catenin pathway, repressed during differentiation) and peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α) (the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS. PGC‐1α induction during differentiation is required for both mitochondrial biogenesis and commitment to the hepatocytic lineage, and TCF7L2 repression is sufficient to increase PGC‐1α expression, mitochondrial biogenesis and OXPHOS activity. We further demonstrate that OXPHOS activity is required for the differentiation toward the hepatocytic lineage, thus providing evidence that bi‐directional interactions control stem cell differentiation and mitochondrial abundance and activity. Stem Cells 2017;35:2184–2197

Submucosal tunneling endoscopic resection (STER) with full-thickness muscle excision for a recurrent para-aortic esophageal leiomyoma after surgery

We report the case of a 49-year-old woman with a recurrent esophageal leiomyoma following two surgical resections. The surgical procedures had been performed 23 and 21 years previously. Follow-up showed lesion recurrence in the mid esophagus (▶Fig. 1 and ▶Fig. 2). Submucosal endoscopic tunneling resection (STER) was preferred to surgery because of the previous interventions. A single shot of 2 g ceftriaxone was administered intravenously prior to the procedure. Submucosal injection, mucosal incision, and tunnel creation was started 5 cm above the lesion. Enucleation was performed using a DualKnife J (Olympus, Tokyo, Japan). The lesion was close to the aorta, so the final dissection was carried out by synchronizing with aortic movements. Full-thickness muscle resection was required to achieve en bloc resection being careful to preserve the esophageal adventitia (▶Video1). The leiomyoma was grasped with a 30-mm snare and was easily removed (▶Fig. 3). Six standard clips (QuickClip Pro; Olympus) were deployed to close the mucosal incision. A computed tomography (CT) scan with swallow study was performed on postoperative day 1; oral diet was restarted on day 2. Histological examination did not show any malignancy. Tumors originating from the muscularis propria require surgery in most cases [1]. STER is a novel approach for the treatment of subepithelial tumors of the gastrointestinal tract. The risk of perforation may reach up to 15% [2]. If the tumor develops from the muscularis propria, preservation of the serosal layer is difficult; circumferential incision of the serosa is therefore often required to complete en bloc resection [3]. Even though a large muscular defect exists, mediastinitis does not occur if the mucosal continuity is maintained [4]. Recurrent esophageal leiomyoma has been anecdotally reported and is usually related to incomplete resection or enlargement of a previously undetected nodule [5]. Here, we report the first STER treatment for recurrent esophageal

Adaptation of liver stiffness measurement depth in bariatric surgery candidates with suspected nonalcoholic fatty liver disease.

Background and aims A thick layer of subcutaneous adipose tissue may lead to an overestimation of liver stiffness by transient elastography. The aim of this study was to assess whether liver stiffness measurement (LSM) was overestimated using an XL probe in patients with severe obesity and, if so, to reprocess the data to the adapted depth to obtain the appropriate LSM (LSMa). Methods A total of 152 obese patients prospectively underwent bariatric surgery and needle liver biopsy. Liver stiffness was measured by transient elastography 15 days before. To determine whether the LSM was overestimated, an expert operator retrospectively determined whether the skin-to-capsula distance was greater than 35 mm by analyzing the hyperechogenicity of ultrasound signals and the measured slope between 35 and 75 mm. In the case of an overestimation, a deeper measurement depth was selected to calculate the LSMa. Results There was an overestimation of the LSM obtained between 35 and 75 mm in 76 patients (50%). Among these patients, the LSMa was obtained between 40 and 75 mm in 49 patients and between 45 and 80 mm in 27 patients. Only the percentage of steatosis was independently and positively correlated with LSM overestimation. The areas under receiver operating characteristic of LSMa was 0.82±0.04 for predicting fibrosis stage F3. The Obuchowski measure was 0.85±0.02. Conclusion The LSM was overestimated in severely obese patients obtained between 35 and 75 mm using an XL probe in 76 patients (50%), but LSM can be performed correctly in these patients after adapting the measurement depth to deeper beneath the patients’ skin.

Opérer les grands obèses dès l’adolescence ?

a Service de médecine des adolescents, hôpital Bicêtre, hôpitaux universitaires Paris Sud, AP–HP, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France b Service de chirurgie viscérale mini-invasive, hôpital Antoine-Béclère, hôpitaux universitaires Paris Sud, AP–HP, 157, rue de la Porte-de-Trivaux, 92140 Clamart, France c Unité médico-chirurgicale d’obésité de l’adolescent, hôpitaux universitaires Paris Sud, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France Disponible en ligne sur

Age-dependent glycosylation of the sodium taurocholate cotransporter polypeptide: From fetal to adult human livers.

Sodium taurocholate cotransporter polypeptide (NTCP), mainly expressed on the sinusoidal membrane of hepatocytes, is one of the major transporters responsible for liver bile acid (BA) re‐uptake. NTCP transports conjugated BA from the blood into hepatocytes and is crucial for correct enterohepatic circulation. Studies have shown that insufficient hepatic clearance of BA correlates with elevated serum BA in infants younger than 1 year of age. In the current study, we investigated human NTCP messenger RNA and protein expression by using reverse‐transcription quantitative polymerase chain reaction and immunoblotting in isolated and cryopreserved human hepatocytes from two different age groups, below and above 1 year of age. Here, we show that NTCP messenger RNA expression is not modulated whereas NTCP protein posttranslational glycosylation is modulated in an age‐dependent manner. These results were confirmed by quantification analysis of NTCP 55‐kDa N‐glycosylated bands, which showed significantly less total NTCP protein in donors below 1 year of age compared to donors older than 1 year. NTCP tissue localization was also analyzed by means of immunofluorescence. This revealed that NTCP cellular localization in fetal samples was mainly perinuclear, suggesting that NTCP is not glycosylated, while its postnatal localization on the plasma membrane is age dependent compared to multidrug resistant protein 2, which is apical starting in fetal life. Conclusion: After birth, the NTCP age‐dependent maturation process requires approximately 1 year to complete NTCP glycosylation in human hepatocytes. Therefore, NTCP late posttranslational glycosylation appears to be important for correct NTCP membrane localization, which might explain physiologic cholestasis in neonatal life and might play a central role for HBV infection after birth. (Hepatology Communications 2018;2:693‐702)