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BACKGROUND:Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. METHODS:To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. RESULTS:Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2-27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. CONCLUSION:The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.

Background & Aims: Tools for the non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) in morbidly obese patients with suspected non-alcoholic fatty liver disease (NAFLD) are an unmet clinical need. We prospectively compared the performance of transient elastography, MRI, and 3 serum scores for the diagnosis of NAFLD, grading of steatosis and detection of NASH in bariatric surgery candidates., Methods: Of 186 patients screened, 152 underwent liver biopsy, which was used as a reference for NAFLD (steatosis [S]>5%), steatosis grading and NASH diagnosis. Biopsies were read by a single expert pathologist. MRI-based proton density fat fraction (MRI-PDFF) was measured in an open-bore, vertical field 1.0T scanner and controlled attenuation parameter (CAP) was measured by transient elastography, using the XL probe. Serum scores (SteatoTest, hepatic steatosis index and fatty liver index) were also calculated., Results: The applicability of MRI was better than that of FibroScan (98% vs. 79%; p <0.0001). CAP had AUROCs of 0.83, 0.79, 0.73 and 0.69 for S>5%, S>33%, S>66% and NASH, respectively. Transient elastography had an AUROC of 0.80 for significant fibrosis (F0-F1 vs. F2-F3). MRI-PDFF had AUROCs of 0.97, 0.95, 0.92 and 0.84 for S>5%, S>33%, S>66% and NASH, respectively. When compared head-to-head in the 97 patients with all valid tests available, MRI-PDFF outperformed CAP for grading steatosis (S>33%, AUROC 0.97 vs. 0.78; p < 0.0003 and S>66%, AUROC 0.93 vs. 0.75; p = 0.0015) and diagnosing NASH (AUROC 0.82 vs. 0.68; p = 0.0056). When compared in "intention to diagnose" analysis, MRI-PDFF outperformed CAP, hepatic steatosis index and fatty liver index for grading steatosis (S>5%, S>33% and S>66%)., Conclusion: MRI-PDFF outperforms CAP for diagnosing NAFLD, grading steatosis and excluding NASH in morbidly obese patients undergoing bariatric surgery., Lay Summary: Non-invasive tests for detecting fatty liver and steatohepatitis, the active form of the disease, have not been well studied in obese patients who are candidates for bariatric surgery. The most popular tests for this purpose are Fibroscan, which can be used to measure the controlled attenuation parameter (CAP), and magnetic resonance imaging, which can be used to measure the proton density fat fraction (MRI-PDFF). We found that, when taking liver biopsy as a reference, MRI-PDFF performed better than CAP for detecting and grading fatty liver as well as excluding steatohepatitis in morbidly obese patients undergoing bariatric surgery., Competing Interests: LC has received lecture’s fees from Abbvie, Echosens, Intercept, Gilead, and Novo Nordisk and consultancy fees from Allergan, Intercept, Gilead, MSD, Novo Nordisk, Pfizer and Servier. No other authors have relevant conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2021 The Authors.)

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.

Glucagon-Like Peptide-1 (GLP-1) undergoes rapid inactivation by dipeptidyl peptidase-4 (DPP4) suggesting that target receptors may be activated by locally produced GLP-1. Here we describe GLP-1 positive cells in the rat and human stomach and found these cells co-expressing ghrelin or somatostatin and able to secrete active GLP-1 in the rats. In lean rats, a gastric load of glucose induces a rapid and parallel rise in GLP-1 levels in both the gastric and the portal veins. This rise in portal GLP-1 levels was abrogated in HFD obese rats but restored after vertical sleeve gastrectomy (VSG) surgery. Finally, obese rats and individuals operated on Roux-en-Y gastric bypass and SG display a new gastric mucosa phenotype with hyperplasia of the mucus neck cells concomitant with increased density of GLP-1 positive cells. This report brings to light the contribution of gastric GLP-1 expressing cells that undergo plasticity changes after bariatric surgeries, to circulating GLP-1 levels.

To retrospectively characterize the molecular features of Non-Small Cell Lung Carcinomas (NSCLC) with peritoneal carcinomatosis (PC), clinicopathological data of 12 patients diagnosed with NSCLC and PC between 2007 and 2016 were collected. Immunohistochemistry and Next Generation Sequencing (NGS) were performed on cases with available material. PC was the initial presentation of NSCLC in 17% of the cases. Overall, patients with PC displayed a poor median survival of 12 weeks. Histology was adenocarcinoma in 11 cases. 37.5% of cases showed PD-L1 immunostaining positivity (50% cut-off). ALK and ROS1 immunostainings were negative. Using NGS, we identified 17 molecular alterations in 9 genes (TP53, KRAS, STK11, BRAF, EGFR, DDR2, ERBB4, SMAD4, CTNNB1) in 88.9% of adenocarcinomas. To the best of our knowledge, 5 of these variants are not referenced in the literature. In conclusion, PC might be the initial presentation of NSCLC. Molecular profiling of our cases did not find any effective targetable alteration, except from high PD-L1 expression.

Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Postoperative upper gastrointestinal fistula (PUGIF) is a devastating complication, leading to high mortality (reaching up to 80%), increased length of hospital stay, reduced health-related quality of life and increased health costs. Nutritional support is a key component of therapy in such cases, which is related to the high prevalence of malnutrition. In the prophylactic setting, enteral nutrition (EN) is associated with a shorter hospital stay, a lower incidence of severe infectious complications, lower severity of complications and decreased cost compared to total parenteral nutrition (TPN) following major upper gastrointestinal (GI) surgery. There is little evidence available for the curative setting after fistula occurrence. We hypothesize that EN increases the 30-day fistula closure rate in PUGIF, allowing better health-related quality of life without increasing the morbidity or mortality., Methods/design: The NUTRILEAK trial is a multicenter, randomized, parallel-group, open-label phase III trial to assess the efficacy of EN (the experimental group) compared with TPN (the control group) in patients with PUGIF. The primary objective of the study is to compare EN versus TPN in the treatment of PUGIF (after esophagogastric resection including bariatric surgery, duodenojejunal resection or pancreatic resection with digestive tract violation) in terms of the 30-day fistula closure rate. Secondary objectives are to evaluate the 6-month postrandomization fistula closure rate, time of first fistula closure (in days), the medical- and surgical treatment-related complication rate at 6 months after randomization, the fistula-related complication rate at 6 months after randomization, the type and severity of early (30 days after randomization) and late fistula-related complications (over 30 days after randomization), 30-day and 6-month postrandomization mortality rate, nutritional status at day 30, day 60, day 90 and day 180 postrandomization, the mean length of hospital stay, the patient's health-related quality of life (by self-assessment questionnaire), oral feeding time and direct costs of treatment. A total of 321 patients will be enrolled., Discussion: The two nutritional supports are already used in daily practice, but most surgeons are reluctant to use the enteral route in case of PUGIF. This study will be the first randomized trial testing the role of EN versus TPN in PUGIF., Trial Registration: ClinicalTrials.gov: NCT03742752. Registered on 14 November 2018.

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett's esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.

Background: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en Y gastric bypass (LRYGB) are commonly performed, but few studies have shown superiority of one strategy over the other., Objective: Simultaneously compare LSG and LRYGB in terms of weight loss and morbimortality over a 36-month follow-up period., Setting: University hospital and bariatric surgery centers, France., Methods: Prospective, comparative study between LSG and RYGBP. The primary endpoint of this study was a joint hypothesis during the 36-month follow-up: the first primary outcome pertained to the frequency of patients with an excess weight loss (EWL) greater than 50% (% EWL>50%) after LSG or RYGB; the second primary outcome was defined as a composite endpoint of at least one major complication. Secondary objectives were regression of comorbidities and improvement in quality of life., Results: Two hundred and seventy-seven patients were included (91 RYGBP, 186 LSG). The mean age was 41.1±11.1 years, and average preoperative body mass index of 45.3±5.5kg/m 2 . After 36months, the %EWL>50% was not inferior in the case of LSG (82.2%) relative to LRYGB (82.1%); while major complications rates were significantly higher in LRYGB (15.4%) vs. LSG (5.4%, P=0.005). After 36months, all secondary objectives were comparable between groups while only gastroesophageal reflux disease (GERD) increased in LSG group and decreased in LRYGB group., Conclusions: LSG was found non-inferior to LRYGB with respect to weight loss and was associated with lower risk of major complications during a 3-year follow-up. But GERD increased in LSG group and decreased in LRYGB group., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: The recent demonstration of prone position's strong benefit on patient survival has rendered proning a major therapeutic intervention in severe ARDS. Uncertainties remain as to whether or not ARDS patients in the postoperative period of abdominal surgery should be turned prone because of the risk of abdominal complications. Our aim was to investigate the prevalence of surgical complications between patients with and without prone position after abdominal surgery., Methods: This study was a multicenter retrospective cohort of patients with ARDS in a context of recent abdominal surgery. Primary outcome was the number of patients who had at least one surgical complication that could be induced or worsened by prone position. Secondary outcomes included effects of prone position on oxygenation. Data from the prone group were compared with those from the supine group (not having undergone at least a prone position session)., Results: Among 98 patients included, 36 (37%) had at least one prone position session. The rate of surgical complications induced or worsened by prone position did not differ between prone and supine groups [respectively, 14 (39%) vs 27 (44%); p = 0.65]. After propensity score application, there was no significant difference between the two groups (OR 0.72 [0.26-2.02], p = 0.54). Revision surgery did not differ between the groups. The first prone session significantly increased PaO 2 /FiO 2 ratio from 95 ± 47 to 189 ± 92 mmHg, p < 0.0001., Conclusion: Prone position of ARDS patients after abdominal surgery was not associated with an increased rate of surgical complication. Intensivists should not refrain from proning these patients.

Bariatric surgery is a well-accepted procedure for severe and massive obesity management. We aimed to determine trends, geographical variations, and factors influencing bariatric surgery and the choice of procedure in France in a large observational study.The Health Insurance Fund for Salaried Workers (Caisse National Assurance Maladie Travailleurs Salariés) covers about 86% of the French population. The Système National d'Information Inter-régimes de l'Assurance Maladie database contains individualized and anonymized patient data on all reimbursements for healthcare expenditure. All types of primary bariatric procedures (Roux-en-Y gastric bypass [RYGB] or omega loop, adjustable gastric banding [AGB], or longitudinal sleeve gastrectomy [LSG]) performed during 2011 to 2013 were systematically recorded. Surgical techniques performed by region of residence and age-range relative risks with 95% confidence intervals of undergoing LSG or RYGB versus AGB were computed.In 2013, LSG was performed more frequently than RYGB and AGB (57% vs 31% and 13%, respectively). A total of 41,648 patients underwent a bariatric procedure; they were predominantly female (82%) with a mean (±standard deviation) age of 40 (±12) years and a body mass index ≥40 kg/m for 68% of them. A total of 114 procedures were performed in patients younger than 18 years and 2381 procedures were performed in patients aged 60 years and older. Beneficiaries of the French universal health insurance coverage for low-income patients were more likely to undergo surgery than the general population. Large nationwide variations were observed in the type choice of bariatric surgical procedures. Significant positive predictors for undergoing RYGB compared to those for undergoing AGB were as follows: referral to a center performing a large number of surgeries or to a public hospital, older age, female gender, body mass index ≥50 kg/m, and treatment for obstructive sleep apnea syndrome, diabetes, or depression. Universal health insurance coverage for low-income patients was inversely correlated with the probability of RYGB.Differences in access to surgery have been observed in terms of the patient's profile, geographical variations, and predictors of types of procedures. Several challenges must be met when organizing the medical care of this growing number of patients, when delivering surgery through qualified centers while assuring the quality of long-term follow-up for all patients., Competing Interests: SC reports past fees for conference or bord meeting from: Novo Nordisk, Lilly, AstraZeneca, Vitalaire, MSD, BMS, Servier, Covidien, Merck Serono, Sanofi, Abbvie, Vifor, Linkup; grants from Novo Nordisk, Echosens. SC is co-funder of a start up (MyGoodLife).

The technically easier one-anastomosis (mini) gastric bypass (MGB) is associated with similar metabolic improvements and weight loss as the Roux-en-Y gastric bypass (RYGB). However, MGB is controversial and suspected to result in greater malabsorption than RYGB. In this study, we compared macronutrient absorption and intestinal adaptation after MGB or RYGB in rats. Body weight and food intake were monitored and glucose tolerance tests were performed in rats subjected to MGB, RYGB, or sham surgery. Carbohydrate, protein, and lipid absorption was determined by fecal analyses. Intestinal remodeling was evaluated by histology and immunohistochemistry. Peptide and amino acid transporter mRNA levels were measured in the remodeled intestinal mucosa and those of anorexigenic and orexigenic peptides in the hypothalamus. The MGB and RYGB surgeries both resulted in a reduction of body weight and an improvement of glucose tolerance relative to sham rats. Hypothalamic orexigenic neuropeptide gene expression was higher in MGB rats than in RYGB or sham rats. Fecal losses of calories and proteins were greater after MGB than RYGB or sham surgery. Intestinal hyperplasia occurred after MGB and RYGB with increased jejunum diameter, higher villi, and deeper crypts than in sham rats. Peptidase and peptide or amino acid transporter genes were overexpressed in jejunal mucosa from MGB rats but not RYGB rats. In rats, MGB led to greater protein malabsorption and energy loss than RYGB. This malabsorption was not compensated by intestinal overgrowth and increased expression of peptide transporters in the jejunum., (Copyright © 2016 the American Physiological Society.)

Background: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC)., Patients and Methods: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival., Results: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%., Conclusion: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: Volumetry is standard method for evaluating the volumes of the right liver (RL), left liver (LL), left lateral segments (LLS), total liver (TL) and future liver remnant (FLR). The aim of this study was to report a simple technique based on measurements of liver angles (angulometry) that can be used to predict liver ratios., Methods: Fifty computed tomography (CT) scans obtained in subjects with normal liver were studied. Four CT scan levels were preselected: level 1 passed by the upper part of the hepatic veins; level 2 passed by the left portal vein branch division; level 3 passed by the right portal vein branch division, and level 4 passed by the gallbladder bed. Left and right tangent lines passing the liver edges were drawn and joined to the centre of the vertebra defining the TL angle. Two lines through, respectively, the plane of the middle hepatic vein and the left portal branches determined the angles of the RL, LL and LLS. Volumetric and angulometric data obtained on levels 2 and 3 in 50 different subjects were compared., Results: Level 2 CT scans represented the most accurate way of obtaining angulometric measurements. The mean ± standard deviation (SD) angles of the TL and LL were 134 ± 12 ° and 55 ± 12 °, respectively. The mean ± SD percentages of the TL represented by the LL in angulometry and volumetry were 38 ± 7% and 36 ± 6%, respectively (non-significant difference). The mean ± SD percentages of the TL represented by the LLS in angulometry and volumetry were 25 ± 4% and 20 ± 3%, respectively (P < 0.05). The mean ± SD overestimation of the percentage of the TL represented by the LLS in angulometry was 2.7 ± 7.0%., Conclusions: Angulometry is a simple and accurate technique that can be used to estimate the ratio of the FLR to TL volume on one or two CT (or magnetic resonance imaging) slices. It can be helpful for clinicians, especially before right or extended right hepatectomy and after right portal vein occlusion techniques., (© 2013 International Hepato-Pancreato-Biliary Association.)

Objective: To clarify the relationships between circulating microparticles (MPs), leukocyte-platelet aggregates (LPAs), obesity, and metabolic abnormalities and evaluate the effect of losing weight on these parameters., Design and Methods: In 151 severely obese women and 60 lean controls, total MPs (annexin-V positive), platelet (annexin V/CD41+) and endothelial (CD31+/CD41-) MPs, and LPAs using flow cytometry, and the presence of metabolic syndrome (MS) were assessed. The effect of weight loss was studied in 32 subjects after a 1 year follow-up., Results: Total microparticle count, platelet MPs (PMPs) and endothelial MPs (EMPs), and neutrophil-platelet aggregates were significantly increased in obese subjects versus lean controls, independently of the MS. Within obese subjects, there was no significant difference between those having and those not having MS. MPs and LPA counts did not vary significantly in subjects who lost 25% of their excess weight., Conclusions: PMPs and EMPs, and LPAs are associated with obesity independently of metabolic abnormalities, but do not significantly change after massive weight loss. Further studies are needed to evaluate the prognostic significance of these observations, as beneficial effects of MPs are currently reported in addition to their initially described deleterious effects., (Copyright © 2013 The Obesity Society.)

Bariatric surgery as laparoscopic Roux-en-Y gastric bypass (LRYGB) is increasing throughout the world and women represent the majority (70%) of patients. Most of them are of reproductive age. As a consequence, surgeons will have to treat more and more pregnant patients with a history of LRYGB for surgical abdominal pain. Reported incidence of small bowel obstruction (SBO) varies from 1.5% to 3.5% after LRYGB including internal hernias, intussusception and volvulus. As two cases of maternal postoperative death have been reported in the literature, diagnosis and surgical treatment shouldn't be delayed especially during pregnancy. To underline the necessity of a rapid diagnosis and surgical treatment, we reported two cases of severe SBO during pregnancy., (© JSCR.)

Malignant hemorrhagic ascites may complicate the terminal evolution of digestive cancers with peritoneal carcinomatosis. It has a bad influence on prognosis and may severely impair patients' quality of life. Palliative laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to treat debilitating malignant ascites. Two cases of peritoneal carcinomatosis causing hemorrhagic ascites and severe anemia that needed iterative blood transfusions are reported. These patients were treated by laparoscopic HIPEC (mitomycin C and cisplatin with an inflow temperature of 43°C), resulting in cessation of peritoneal bleeding. No postoperative complication or relapse of ascites occurred during the following months. No more blood transfusion was needed. Laparoscopic HIPEC might be an effective and safe therapeutic option to consider in patients with malignant hemorrhagic ascites.

Background: Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma., Methods/design: The MIRO trial is an open, controlled, prospective, randomised multicentre phase III trial. Patients in study arm A will receive laparoscopic-assisted oesophagectomy, i.e., a transthoracic oesophagectomy with two-field lymphadenectomy and laparoscopic gastric mobilisation. Patients in study arm B will receive the same procedure, but with the conventional open abdominal approach. The primary objective of the study is to evaluate the major postoperative 30-day morbidity. Secondary objectives are to assess the overall 30-day morbidity, 30-day mortality, 30-day pulmonary morbidity, disease-free survival, overall survival as well as quality of life and to perform medico-economic analysis. A total of 200 patients will be enrolled, and two safety analyses will be performed using 25 and 50 patients included in arm A., Discussion: Postoperative morbidity remains high after oesophageal cancer surgery, especially due to major pulmonary complications, which are responsible for 50% of the postoperative deaths. This study represents the first randomised controlled phase III trial to evaluate the benefits of the minimally invasive approach with respect to the postoperative course and oncological outcomes in oesophageal cancer surgery., Trial Registration: NCT00937456 (ClinicalTrials.gov).

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population. Therefore, the aim of this study was to clarify the determinants of metabolic disorders in severely obese women. We performed a cross-sectional study in 237 severely obese women (BMI >35 kg/m(2)). We assessed total body fat mass and fat distribution by anthropometric measurements (BMI and waist-to-hip ratio (WHR)) and by dual-energy X-ray absorptiometry (DXA). In 22 women, we measured subcutaneous and visceral adipocyte size on surgical biopsies. Mean BMI was 44 +/- 7 kg/m(2) (range 35-77), mean age 37 +/- 11 years (range 18-61). Lipid parameters (triglycerides, high-density lipoprotein cholesterol) and IR markers (fasting insulin and homeostasis model assessment (HOMA) index) correlated with fat distribution, whereas inflammatory parameters (C-reactive protein, fibrinogen) correlated only with total fat mass. An association was observed between android fat distribution and adipocyte hypertrophy. Visceral adipocyte hypertrophy was associated with both IR and hypertension, whereas subcutaneous fat-cell size was linked only to hypertension. Our results obtained in a large cohort of women showed that fat distribution still predicts metabolic abnormalities in severe obesity. Furthermore, we found a cluster of associations among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy.

Aims/hypothesis: Obesity is associated with adipose tissue inflammation. The CD40 molecule, TNF receptor superfamily member 5 (CD40)/CD40 ligand (CD40L) pathway plays a role in the onset and maintenance of the inflammatory reaction, but has not been studied in human adipose tissue. Our aim was to examine CD40 expression by human adipocytes and its participation in adipose tissue inflammation., Methods: CD40 expression was investigated in human whole adipose tissue and during adipocyte differentiation by real-time PCR, Western blot and immunohistochemistry. The CD40/CD40L pathway was studied using recombinant CD40L (rCD40L) in adipocyte culture and neutralising antibodies in lymphocyte/adipocyte co-culture., Results: CD40 mRNA levels in subcutaneous adipose tissue were higher in the adipocyte than in the stromal-vascular fraction. CD40 expression was upregulated during adipocyte differentiation. Addition of rCD40L to adipocytes induced mitogen activated protein kinase (MAPK) activation, stimulated inflammatory adipocytokine production, and decreased insulin-induced glucose transport in parallel with a downregulation of IRS1 and GLUT4 (also known as SCL2A4). rCD40L decreased the expression of lipogenic genes and increased lipolysis. CD40 mRNA levels were significantly higher in subcutaneous adipose tissue than in visceral adipose tissue of obese patients and were positively correlated with BMI, and with IL6 and leptin mRNA levels. Lymphocyte/adipocyte co-culture led to an upregulation of proinflammatory adipocytokines and a downregulation of leptin and adiponectin. Physical separation of the two cell types attenuated these effects, suggesting the involvement of a cell-cell contact. Blocking the CD40/CD40L interaction with neutralising antibodies reduced IL-6 secretion from adipocytes., Conclusions/interpretation: Adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance. T lymphocytes regulate adipocytokine production through both the release of soluble factor(s) and heterotypic contact with adipocytes involving CD40.

Objective: The expansion of adipose tissue is linked to the development of its vasculature. However, the regulation of adipose tissue angiogenesis in humans has not been extensively studied. Our aim was to compare the angiogenesis associated with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from the same obese patients in an in vivo model., Research Design and Methods: Adipose tissue samples from visceral (VAT) and subcutaneous (SAT) sites, obtained from 36 obese patients (mean BMI 46.5 kg/m(2)) during bariatric surgery, were layered on chick chorioallantoïc membrane (CAM)., Results: Both SAT and VAT expressed angiogenic factors without significant difference for vascular endothelial growth factor (VEGF) expression. Adipose tissue layered on CAM stimulated angiogenesis. Angiogenic stimulation was macroscopically detectable, with engulfment of the samples, in 39% and was evidenced by angiography in 59% of the samples. A connection between CAM and adipose tissue vessels was evidenced by immunohistochemistry, with recruitment of both avian and human endothelial cells. The angiogenic potency of adipose tissue was not related to its localization (with an angiogenic stimulation in 60% of SAT samples and 61% of VAT samples) or to adipocyte size or inflammatory infiltrate assessed in adipose samples before the graft on CAM. Stimulation of angiogenesis by adipose tissue was nearly abolished by bevacizumab, which specifically targets human VEGF., Conclusions: We have established a model to study the regulation of angiogenesis by human adipose tissue. This model highlighted the role of VEGF in angiogenesis in both SAT and VAT.

Introduction: The aim of this study was to evaluate the results of an aggressive strategy in patients presenting peritoneal carcinomatosis (PC) from colorectal cancer with or without liver metastases (LMs) treated with cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Patients and Methods: The population included 43 patients who had 54 CS+HIPEC for colorectal PC from 1996 to 2006. Sixteen patients (37%) presented LMs. Eleven patients (25%) presented occlusion at the time of PC diagnosis. Ascites was present in 12 patients (28%). Seventy-seven percent of the patients were Gilly 3 (diffuse nodules, 5-20 mm) and Gilly 4 (diffuse nodules>20 mm). The main endpoints were morbidity, mortality, completeness of cancer resection (CCR), and actuarial survival rates., Results: The CS was considered as CCR-0 (no residual nodules) or CCR-1 (residual nodules <5 mm) in 30 patients (70%). Iterative procedures were performed in 26% of patients. Three patients had prior to CS + HIPEC, 10 had concomitant minor liver resection, and 3 had differed liver resections (2 right hepatectomies) 2 months after CS + HIPEC. The mortality rate was 2.3% (1 patient). Seventeen patients (39%) presented one or multiple complications (per procedure morbidity = 31%). Complications included deep abscess (n = 6), wound infection (n = 5), pleural effusion (n = 5), digestive fistula (n = 4), delayed gastric emptying syndrome (n = 4), and renal failure (n = 3). Two patients (3.6%) were reoperated. The median survival was 38.4 months (CI, 32.8-43.9). Actuarial 2- and 4-year survival rates were 72% and 44%, respectively. The survival rates were not significantly different between patients who had CS + HIPEC for PC alone (including the primary resection) versus those who had associated LMs resection (median survival, 35.3 versus 36.0 months, P = 0.73)., Conclusion: Iterative CS + HIPEC is an effective treatment in PC from colorectal cancer. The presence of resectable LMs associated with PC does not contraindicate the prospect of an oncologic treatment in these patients.

Objective: To determine whether temporary occlusion of the main pancreatic duct with human fibrin glue decreases the incidence of intra-abdominal complications after pancreatoduodenectomy (PD) or distal pancreatectomy (DP)., Summary Background Data: To the authors' knowledge, there are no randomized studies comparing outcomes after pancreatic resection with or without main pancreatic duct occlusion by injection of fibrin glue. Of three nonrandomized studies, two reported no fistulas after intracanal injection and ductal occlusion with fibrin glue after PD with immediate pancreatodigestive anastomosis, while another study reported no protective effect of glue injection., Methods: This prospective, randomized, single-blinded, multicenter study, conducted between January 1995 and January 1999, included 182 consecutive patients undergoing PD followed by immediate pancreatic anastomosis or DP, whether for benign or malignant tumor or for chronic pancreatitis. One hundred two underwent pancreatic resection followed by ductal occlusion with fibrin glue (made slowly resorbable by the addition of aprotinin); 80 underwent resection without ductal occlusion. The main end point was the number of patients with one or more of the following intra-abdominal complications: pancreatic or other digestive tract fistula, intra-abdominal collections (infected or not), acute pancreatitis, or intra-abdominal or digestive tract hemorrhage. Severity factors included postoperative mortality, repeat operations, and length of hospital stay., Results: The two groups were similar in pre- and intraoperative characteristics except that there were significantly more patients in the ductal occlusion group who were receiving octreotide, who had reinforcement of their anastomosis by fibrin glue, and who had fibrotic pancreatic stumps. However, the rate of patients with one or more intra-abdominal complications, and notably with pancreatic fistula, did not differ significantly between the two groups. There was still no significant difference found after statistical adjustment for these patient characteristic discrepancies, confirming the inefficacy of fibrin glue. The rate of intra-abdominal complications was significantly higher in the presence of a normal, nonfibrotic pancreatic stump and main pancreatic duct diameter less than 3 mm, whereas reinforcement of the anastomosis with fibrin glue or use of octreotide did not influence outcome. In multivariate analysis, however, normal pancreatic parenchyma was the only independent risk factor for intra-abdominal complications. No significant differences were found in the severity of complications between the two groups., Conclusions: Ductal occlusion by intracanal injection of fibrin glue decreases neither the rate nor the severity of intra-abdominal complications after pancreatic resection.