Right Colectomy with Absorbable Mesh Repair as a Salvage Solution for the Management of Giant Incisional Hernia with Loss of Domain: Results of a Bicentric Study.

BACKGROUND: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence. METHODS: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging. RESULTS: Eleven patients were included. The mean BMI was 43 kg/m2 (23-52 kg/m2). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%. CONCLUSIONS: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material.

Major microbiota dysbiosis in severe obesity: fate after bariatric surgery.

OBJECTIVES: Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes. DESIGN: Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included. RESULTS: Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1 year postsurgery, but most RYGB patients remained with low MGR 1 year post-BS, despite greater metabolic improvement than AGB patients. CONCLUSIONS: We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome-host interactions in severe obesity. TRIAL REGISTRATION NUMBER: NCT01454232.

Akkermansia muciniphila abundance is lower in severe obesity, but its increased level after bariatric surgery is not associated with metabolic health improvement.

The gut bacterial species Akkermansia muciniphila is associated with a healthier clinical profile. The purpose of this study was to determine the association between A. muciniphila and glucose homeostasis in patients undergoing bariatric surgery (BS): gastric banding (GB) or Roux-en-Y gastric bypass (RYGB). This nonrandomized prospective study included 65 women with severe obesity. Longitudinal analysis included subjects for whom A. muciniphila data were available at follow-up [1, 3, and 12 mo; GB (n = 10) or RYGB (n = 11)]. Glucose homeostasis markers were measured under fasting conditions (glucose, insulin, and HbA1c) or during an oral glucose tolerance test. Fecal microbiota was analyzed using shotgun metagenomics, and A. muciniphila relative abundance was assessed with 16S rRNA quantitative PCR. A. muciniphila relative abundance was significantly lower in severe obesity [mean body mass index, 45.7 kg/m2 (SD 5.4)] than in moderate obesity [33.2 kg/m2 (SD 3.8)] but not associated with glucose homeostasis markers. A significant increase in A. muciniphila relative abundance after RYGB was not correlated with metabolic improvement. Baseline A. muciniphila abundance was correlated with bacterial gene richness and was highest in the high-richness Ruminococcaceae enterotype. A. muciniphila increased in relative abundance after BS in patients with low baseline A. muciniphila abundance, especially those with a Bacteroides type 2 enterotype classification. Although decreased in severe obesity, relative abundance of A. muciniphila was not associated with glucose homeostasis before or after BS. A certain level of A. muciniphila abundance might be required to observe a beneficial link to health. The severity of obesity and gut dysbiosis may partly explain the discrepancy with previous findings in less obese populations.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. DESIGN: Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. RESULTS: Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). CONCLUSIONS: These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators.

The advanced-DiaRem score improves prediction of diabetes remission 1 year post-Roux-en-Y gastric bypass.

AIMS/HYPOTHESIS: Not all people with type 2 diabetes who undergo bariatric surgery achieve diabetes remission. Thus it is critical to develop methods for predicting outcomes that are applicable for clinical practice. The DiaRem score is relevant for predicting diabetes remission post-Roux-en-Y gastric bypass (RYGB), but it is not accurate for all individuals across the entire spectrum of scores. We aimed to develop an improved scoring system for predicting diabetes remission following RYGB (the Advanced-DiaRem [Ad-DiaRem]). METHODS: We used a retrospective French cohort (n = 1866) that included 352 individuals with type 2 diabetes followed for 1 year post-RYGB. We developed the Ad-DiaRem in a test cohort (n = 213) and examined its accuracy in independent cohorts from France (n = 134) and Israel (n = 99). RESULTS: Adding two clinical variables (diabetes duration and number of glucose-lowering agents) to the original DiaRem and modifying the penalties for each category led to improved predictive performance for Ad-DiaRem. Ad-DiaRem displayed improved area under the receiver operating characteristic curve and predictive accuracy compared with DiaRem (0.911 vs 0.856 and 0.841 vs 0.789, respectively; p = 0.03); thus correcting classification for 8% of those initially misclassified with DiaRem. With Ad-DiaRem, there were also fewer misclassifications of individuals with mid-range scores. This improved predictive performance was confirmed in independent cohorts. CONCLUSIONS/INTERPRETATION: We propose the Ad-DiaRem, which includes two additional clinical variables, as an optimised tool with improved accuracy to predict diabetes remission 1 year post-RYGB. This tool might be helpful for personalised management of individuals with diabetes when considering bariatric surgery in routine care, ultimately contributing to precision medicine.

The effect of morbid obesity on morphine glucuronidation.

The purpose of the present work was to study the change in morphine metabolic ratio in obese subjects before and after Roux-en-Y Gastric Bypass (RYGB) and to identify clinical and/or biological factors associated with this change. The pharmacokinetics (PK) of oral morphine (30mg), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) was performed in patients before (n=25; mean BMI=43.2 (35.4-61.9)kg/m2), 7-15days (n=16) and 6 months after RYGB (n=19; mean BMI=32.3 (25.4-46.0)kg/m2). Morphine Cmax and AUC0-inf were significantly increased and morphine Tmax significantly shortened at 6 months after RYGB compared with preoperative data, indicating an important increase in the rate and extent of morphine absorption. The morphine metabolic ratio 0-inf M3G+M6G/Morphine, decreased significantly from the preoperative to 6 months postoperative period with an average of -26% (range -74%; +21%; p=0.004), but not in the immediate post-operative period. The change in morphine metabolic ratio was associated with a change in BMI, fat mass in kg, and triglyceride levels (rho=0.5, p≤0.04). The degree of change in several markers of low-grade inflammation, or the level of liver steatosis and fibrosis before surgery, was not associated with the change in morphine metabolic ratios. Our findings indicate that RYGB-induced weight loss significantly decreases morphine metabolic ratio, arguing for an effect of morbid obesity on glucuronidation. With glucuronide exposure at 6 months similar to preoperative values, a higher morphine AUC0-inf should encourage reducing morphine dosage in patients undergoing RYGB and chronically receiving immediate-release oral morphine.

Oral Morphine Pharmacokinetic in Obesity: The Role of P-Glycoprotein, MRP2, MRP3, UGT2B7, and CYP3A4 Jejunal Contents and Obesity-Associated Biomarkers.

The objective of our work was to study the association between the jejunal expression levels of P-gp, MRP2, MRP3, UGT2B7, CYP3A4, the ABCB1 c.3435C > T polymorphism, and several obesity-associated biomarkers, as well as oral morphine and glucuronides pharmacokinetics in a population of morbidly obese subjects. The pharmacokinetics of oral morphine (30 mg) and its glucuronides was performed in obese patients candidate to bariatric surgery. A fragment of jejunal mucosa was preserved during surgery. Subjects were genotyped for the ABCB1 single nucleotide polymorphism (SNP) c.3435C > T. The subjects were 6 males and 23 females, with a mean body mass index of 44.8 (35.4-61.9) kg/m(2). The metabolic ratios AUC0-inf M3G/morphine and AUC0-inf M6G/morphine were highly correlated (rs = 0.8, p < 0.0001) and were 73.2 ± 24.6 (34.7-137.7) and 10.9 ± 4.1 (3.8-20.6). The pharmacokinetic parameters of morphine and its glucuronides were not associated with the jejunal contents of P-gp, CYP3A4, MRP2, and MRP3. The jejunal content of UGT2B7 was positively associated with morphine AUC0-inf (rs = 0.4, p = 0.03). Adiponectin was inversely correlated with morphine Cmax (rs = -0.44, p = 0.03). None of the factors studied was associated with morphine metabolic ratios. The interindividual variability in the jejunal content of drug transporters and metabolizing enzymes, the ABCB1 gene polymorphism, and the low-grade inflammation did not explain the variability in morphine and glucuronide exposure. High morphine metabolic ratio argued for an increased morphine glucuronidation in morbidly obese patients.

Quantitative Atlas of Cytochrome P450, UDP-Glucuronosyltransferase, and Transporter Proteins in Jejunum of Morbidly Obese Subjects.

Protein expression levels of drug-metabolizing enzymes and transporters in human jejunal tissues excised from morbidly obese subjects during gastric bypass surgery were evaluated using quantitative targeted absolute proteomics. Protein expression levels of 15 cytochrome P450 (CYP) enzymes, 10 UDP-glucuronosyltransferase (UGT) enzymes, and NADPH-P450 reductase (P450R) in microsomal fractions from 28 subjects and 49 transporters in plasma membrane fractions from 24 of the same subjects were determined using liquid chromatography-tandem mass spectrometry. Based on average values, UGT1A1, UGT2B15, UGT2B17, SGLT1, and GLUT2 exhibited high expression levels (over 10 fmol/µg protein), though UGT2B15 expression was detected at a high level in only one subject. CYP2C9, CYP2D6, CYP3A5, UGT1A6, P450R, ABCG2, GLUT5, PEPT1, MCT1, 4F2 cell-surface antigen heavy chain (4F2hc), LAT2, OSTα, and OSTß showed intermediate levels (1-10 fmol/µg protein), and CYP1A1, CYP1A2, CYP1B1, CYP2C18, CYP2C19, CYP2J2, CYP3A7, CYP4A11, CYP51A1, UGT1A3, UGT1A4, UGT1A8, UGT2B4, ABCC1, ABCC4, ABCC5, ABCC6, ABCG8, TAUT, OATP2A1, OATP2B1, OATP3A1, OATP4A1, OCTN1, CNT2, PCFT, MCT4, GLUT4, and SLC22A18 showed low levels (less than 1 fmol/µg protein). The greatest interindividual difference (364-fold) was detected for UGT2B17. However, differences in expression levels of other quantified UGTs (except UGT2B15 and UGT2B17), CYPs (except CYP1A1 and CYP3A5), and P450R, and all quantified transporters, were within 10-fold. Expression levels of CYP1A2 and GLUT4 were significantly correlated with body-mass index. The levels of 4F2hc showed significant gender differences. Smokers showed increased levels of UGT1A1 and UGT1A3. These findings provide a basis for understanding the changes in molecular mechanisms of jejunal metabolism and transport, as well as their interindividual variability, in morbidly obese patients.

Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity.

BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning with fibrosis in severe cases, and high prevalence in obesity. We aimed at defining NASH signature in morbid obesity by mass spectrometry-based lipidomic analysis. METHODS: We analyzed systemic blood before and 12 months after bariatric surgery, along with portal blood and adipose tissue lipid efflux collected from obese women at the time of surgery (9 structural classes, 150 species). RESULTS: Increased concentrations of several glycerophosphocholines (PC), glycerophosphoethanolamines (PE), glycerophosphoinositols (PI), glycerophosphoglycerols (PG), lyso-glycerophosphocholines (LPC), and ceramides (Cer) were detected in systemic circulation of NASH subjects. Post-surgery weight loss (12 months) improved the levels of liver enzymes, as well as several lipids, but most PG and Cer species remained elevated. Analysis of lipids from hepatic portal system at the time of surgery revealed limited lipid alterations compared to systemic circulation, but PG and PE classes were found significantly increased in NASH subjects. We evaluated the contribution of visceral adipose tissue to lipid alterations in portal circulation by measuring adipose tissue lipid efflux ex vivo, and observed only minor alterations in NASH subjects. Interestingly, integration of clinical and lipidomic data (portal and systemic) led us to define a NASH signature in which lipids and clinical parameters are equal contributors. CONCLUSIONS: Circulatory (portal and systemic) phospholipid profiling and clinical data defines NASH signature in morbid obesity. We report weak contribution of visceral adipose tissue to NASH-related portal lipid alterations, suggesting possible contribution from other organs draining into hepatic portal system.

Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery.

BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS). METHODS: Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS < 5 (2.4(2.0-3.1) vs 1.9(1.5-2.3) mg/L, P < 0.001) and in patients with bridging fibrosis (F ≥ 3) compared with lower fibrosis stages (2.6(2.0-4.9) vs 2.0(1.5-2.4) mg/L, P = 0.001). Preoperative sCD163 was independently associated with both the NAS (P = 0.002) and the fibrosis score (P = 0.024). sCD163 decreased after BS and was greatly reduced after 12 months, more rapidly so in patients with NAS ≥ 5 (P < 0.001) and non-alcoholic steatohepatitis (NASH) according to the FLIP algorithm (P = 0.03). Immunohistochemistry showed CD163-positive macrophages aligning fat-laden hepatocytes and forming microgranulomas in patients with NASH. CD163 mRNA expression did not vary with NAS. CONCLUSION: sCD163 increased in parallel with the severity of NAFLD in morbid obesity, indicating macrophage activation. BS reduced sCD163 even in patients with severe liver injury and fibrosis, suggesting full reversibility of macrophage activation associated with improved insulin sensitivity.

Anatomical and CT approach of the adipose tissue: application in morbid obesity.

PURPOSE: The importance and proportion of visceral adipose tissue (VAT) represent the best criterion to define obesity. Because VAT value is difficult to obtain in clinical practice, the indication for bariatric surgery is still based at present on Body Mass index (BMI), even though BMI is a poor predictor of obesity-related morbid complications. This correlation study aimed at determining a simple and accurate computed tomography (CT) anatomic marker, which can be easily used clinically, well correlated with the volume of VAT and consequently with morbid complications. METHODS: We studied 108 CT scans of patients presenting with morbid obesity. Several simplified measures (external and internal abdominal diameters and circumferences) were conducted on CT scan view, going through the fourth lumbar vertebra (L4), in addition to various vertebral measurements (area of the vertebra, sagittal and transversal diameters), VAT and subcutaneous adipose tissue (SAT). Then, we reported the simplified measures values on the vertebral areas, and we calculated the Bertin index. Finally, we conducted a correlation study between all variables to obtain accurate VAT measurements. RESULTS: The internal abdominal circumference and the Bertin index showed the best correlations with VAT in morbidly obese patients (r = 0.84 and 0.85, respectively). BMI and anthropometric measures were not correlated with VAT. CONCLUSION: CT scan study allows to simply approximate VAT value in morbidly obese patients. An abdominal CT scan could be part of the tests used in the evaluation of obese patients to base therapeutic strategies on VAT values and not on BMI as it is the case today.

Is laparoscopy a safe approach for diffuse appendicular peritonitis? Feasibility and determination of risk factors for post-operative intra-abdominal abscess.

BACKGROUND: Several studies have assessed feasibility and early outcomes of the laparoscopic approach for complicated appendicitis (CA). However, these studies suffer from limitations due to the heterogeneous definitions used for CA. No studies have assessed feasibility and early post-operative outcomes of the laparoscopic approach in the specific management of diffuse appendicular peritonitis (DAP). Consequently, outcomes of the laparoscopic approach for the management of DAP are poorly documented. METHODS: The laparoscopic approach is the first-line standardised procedure used by our team for the management of DAP. All patients (aged >16 years) who underwent laparoscopy for DAP (CA with the presence of purulent fluid with or without fibrin membranes in at least a hemi abdomen) between 2004 and 2012 were prospectively included. Post-operative outcomes were analysed according to the Clavien-Dindo classification. RESULTS: Laparoscopy for DAP was performed for 141 patients. Mean age was 39.6 ± 20 (16-92) years. A total of 45 patients (31.9%) had pre-operative contracture. The mean pre-operative leukocyte count was 14,900 ± 4,380 mm(-3). The mean pre-operative C-reactive protein (CRP) serum concentration was 135 ± 112 (2-418) mg/dl. The conversion rate was 3.5%. The mean operative time was 80 ± 27 (20-180) min. There were no deaths. The rate of grade III morbidity was 6.5%. Ten patients (7.1%) experienced intra-abdominal abscess (IAA); seven of these cases were treated conservatively. The mean length of hospital stay was 6.9 ± 5 (2-36) days. A pre-operative leukocyte count >17,000 mm(-3), and CRP serum concentration >200 mg/dl were significant predictive factors for IAA in multivariate analyses [odds ratio (OR) 25.0, 95% confidence interval (CI) 2.4-250, p = 0.007 and OR 16.4, 95% CI 1.6-166, p = 0.02, respectively]. CONCLUSION: The laparoscopic approach for DAP is a safe and feasible procedure with a low conversion rate and an acceptable rate of IAA in view of the severity of the disease. Pre-operative leukocyte counts >17,000 mm(-3) and pre-operative CRP serum concentrations >200 mg/dl indicate a high risk of IAA.

Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and being overweight is a significant risk factor. The aim was to build an algorithm along with a scoring system for histopathologic classification of liver lesions that covers the entire spectrum of lesions in morbidly obese patients. A cohort of 679 obese patients undergoing liver biopsy at the time of bariatric surgery was studied. An algorithm for segregating lesions into normal liver, NAFLD, or nonalcoholic steatohepatitis (NASH) was built based on semiquantitative evaluation of steatosis, hepatocellular ballooning, and lobular inflammation. For each case, the SAF score was created including the semiquantitative scoring of steatosis (S), activity (A), and fibrosis (F). Based on the algorithm, 230 obese patients (34%) were categorized as NASH, 291 (43%) as NAFLD without NASH, and 158 (23%) as not NAFLD. The activity score (ballooning + lobular inflammation) enabled discriminating NASH because all patients with NASH had A ≥ 2, whereas no patients with A < 2 had NASH. This score was closely correlated with both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P < 0.0001, analysis of variance [ANOVA]). Comparison of transaminase levels between patients with normal liver and pure steatosis did not reveal significant differences, thus lending support to the proposal not to include steatosis in the activity score but to report it separately in the SAF score. In the validation series, the interobserver agreement for the diagnosis of NASH was excellent (κ = 0.80) between liver pathologists. There was no discrepancy between the initial diagnosis and the diagnosis proposed using the algorithm. CONCLUSION: We propose a simple but robust algorithm for categorizing liver lesions in NAFLD patients. Because liver lesions in obese patients may display a continuous spectrum of histologic lesions, we suggest describing liver lesions using the SAF score.

Lateral incisional hernia repair by the retromuscular approach with polyester standard mesh: topographic considerations and long-term follow-up of 61 consecutive patients.

BACKGROUND: Because of the lack of published data and the relative rarity of lateral incisional hernia (LIH), their repair remains a major challenge for surgeons. The aim of the present study was to evaluate the outcome of LIH treated by the retromuscular approach (RMA) with a polyester standard mesh. METHODS: Sixty-one patients were treated between June 2000 and November 2007 in an academic tertiary referral center using one standardized surgical technique and one type of mesh. Lumbar incisional hernia was excluded. All data were prospectively culled. The early complications and recurrence rates were evaluated. RESULTS: There were 14 (23%) subcostal, 12 (19.6%) flank, and 35 (57.4%) iliac fossa LIH. The mean patient age was 57 years, and 60% were male. The average width of the defect was 7.6 cm and the overall defect size averaged 56 cm². Seventeen patients (28%) had had previous LIH repair. Ten patients had double hernia locations (midline and lateral) repaired simultaneously. The average operative time and hospital stay were 136 min and 7 days, respectively. The early complications rate was 18%. Four patients required reoperation. There were no mesh infections. The median follow-up was 47 months (range: 1-125 months). Recurrence was observed in three patients (4.9%). CONCLUSIONS: LIH repair by RMA with a polyester heavyweight mesh proves to be a safe treatment with a moderate complication rate and a low infection rate, even in the treatment of large or multifocal parietal defects.

Bariatric procedures including Roux-en-Y gastric bypass in French adolescents.

INTRODUCTION: In France, approximately 100 obese adolescents undergo a bariatric procedure every year. To date, only data from laparoscopic adjustable gastric banding (LAGB) or sleeve gastrectomy (SG) have been published. Our objective was to report the outcomes of a series of French obese adolescents who underwent a Roux-en-Y gastric bypass (RYGB). METHODS: We included all obese adolescents aged 13-19 years who underwent RYGB in our department from 2008 with at least 2 years of follow-up after surgery. We analyzed the course of the anthropometric data, comorbidities, and subsequent adverse events. RESULTS: Starting in September 2008, out of 93 obese adolescents who requested bariatric surgery, 39 (35%) underwent a bariatric procedure. From these adolescents, 2-year follow-up data were available for 26 patients who had a RYGB. At the time of surgery, the mean patient age was 17.4 years (standard deviation [SD]=1.4) and the body mass index (BMI) was 52.0 kg/m² (SD=7.8). One patient was lost to follow-up. At 2 years after surgery,  the mean BMI was 35.7 kg/m² (SD=9.4) with a mean decrease in BMI of 31.9% (SD=11.6). Comorbidities improved for most of the patients: high blood pressure (2/2) and pseudotumor cerebri (1/1) were cured after surgery, and dyslipidemia improved globally. The complications observed were anemia, abdominal pain requiring celioscopy (n = 2), and oxalic nephrolithiasis. CONCLUSION: Only one third of the obese adolescents requesting bariatric surgery were operated on. Our series including exclusively obese adolescents who underwent an RYGB presents the results of this technique on weight loss and comorbidities; mechanical and nutritional complications remain uncommon. These results are similar to those obtained in studies of adult patients.

Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese.

BACKGROUND & AIMS: Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues. METHODS: One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH. RESULTS: Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile (p values ≤0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue. CONCLUSIONS: In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.

Structural and inflammatory heterogeneity in subcutaneous adipose tissue: relation with liver histopathology in morbid obesity.

BACKGROUND & AIMS: In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly associated with metabolic co-morbidities of obesity. We recently showed that the severity of histological liver lesions related to obesity increases with the amount of macrophage accumulation in visceral adipose tissue (VAT), while no association was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into two layers, i.e. superficial (sSAT) and deep (dSAT). The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alterations in obesity. METHODS: Biopsies of the liver, sSAT, dSAT, and VAT were collected in 45 subjects with morbid obesity (age 43.7±1.6 years; BMI 48.5±1.2kg/m(2)) during bariatric surgery. Large scale gene expression analysis was performed to identify the pathways that discriminate sSAT from dSAT. Adipose tissue macrophages were quantified by immunohistochemistry using HAM56 antibody in subjects scored for liver histopathology. RESULTS: An inflammatory gene pattern discriminates between sSAT and dSAT. dSAT displayed an intermediate level of macrophage accumulation between sSAT and VAT. The abundance of macrophages in dSAT, but not in sSAT, was significantly increased in patients with non-alcoholic steatohepatitis (NASH) and/or fibroinflammatory hepatic lesions. CONCLUSIONS: These data show distinct gene signature and macrophage abundance in the two compartments of SAT, with dSAT more closely related to VAT than to sSAT in terms of inflammation and relation with the severity of liver diseases in morbid obesity.

Retromuscular mesh repair of midline incisional hernia with polyester standard mesh: monocentric experience of 261 consecutive patients with a 5-year follow-up.

BACKGROUND: Midline incisional hernia (MIH) repair remains a major challenge for surgeons. Multiple procedures and types of mesh to treat incisional hernia are available. We evaluated outcomes of MIH treated by retromuscular mesh repair (RMR) using a polyester standard prosthesis. PATIENTS: A total of 262 patients were treated for MIH by RMR between June 2000 and November 2007 in an academic tertiary referral center using the same standardized surgical technique and one type of mesh. The early complications and recurrence rate were evaluated. RESULTS: The average patient age was 57 years; 51% were women. The mean width was 7.8 cm and defect size was 61 cm². Previous MIH repair had been performed in 23% of the patients. Average hospital stay was 7 days. Of the 262 patients studied, 34 patients (13%) developed early complications, and 16 required reoperation for various indications. Early mesh infection occurred in 2 patients (0.8%) requiring mesh removal. The mean follow-up was 58 months. Recurrence was observed in 8 patients (3%) with an average delay of 19 months. There was a significant difference in terms of recurrence in patients with mesh infection versus the group who did not develop infection (2/2 patients versus 6/259; P < 0.001). CONCLUSIONS: Our results suggest that RMR with a polyester standard prosthesis for MIH remains a safe "classic" treatment with a moderate complication rate and a low infection and recurrence rate, even in large incisional hernia.

Benefits of massive weight loss on symptoms, systemic inflammation and cartilage turnover in obese patients with knee osteoarthritis.

OBJECTIVE: To investigate the effect of massive weight loss on (1) knee pain and disability, (2) low-grade inflammation and metabolic status and (3) joint biomarkers in obese patients with knee osteoarthritis (OA). METHODS: 140 patients involved in a gastric surgery programme were screened for painful knee OA, and 44 were included (age 44 ± 10.3 years, body mass index (BMI) 50.7 ± 7.2 kg/m(2)). Clinical data and biological samples were collected before and 6 months after surgery. RESULTS: Before surgery, interleukin 6 (IL-6) levels were correlated with levels of high-sensitivity C reactive protein (hsCRP) (p=0.006) and Helix-II (p=0.01), a biomarker of cartilage turnover, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score (p=0.03). Surgery resulted in substantial decrease in BMI (-20%). Levels of insulin and insulin resistance were decreased at 6 months. Knee pain decreased after surgery (24.5 ± 21 mm vs 50 ± 26.6 mm; p<0.001), and scores on all WOMAC subscales were improved. Levels of IL-6 (p<0.0001), hsCRP (p<0.0001), orosomucoid (p<0.0001) and fibrinogen (p=0.04) were decreased after surgery. Weight loss resulted in a significant increase in N-terminal propeptide of type IIA collagen levels (+32%; p=0.002), a biomarker of cartilage synthesis, and a significant decrease in cartilage oligomeric matrix protein (COMP) (-36%; p<0.001), a biomarker of cartilage degradation. Changes in COMP concentration were correlated with changes in insulin levels (p=0.02) and insulin resistance (p=0.05). CONCLUSION: Massive weight loss improves pain and function and decreases low-grade inflammation. Change in levels of joint biomarkers with weight loss suggests a structural effect on cartilage.

Bevacizumab-induced small bowel perforation in a patient with breast cancer without intraabdominal metastases.

A 53-years-old woman presented with sudden abdominal pain. One year before, she was diagnosed an inflammatory ductal carcinoma of the left breast (T3N0M0) and received 6 cycles of epirubicin and cyclophosphamide followed by 9 cycles of paclitaxel. A radical left mastectomy with lymphadenectomy was performed. On histopathology, the invasive ductal carcinoma was poorly differentiated, histological grade III without lymphovascular emboli, expressing E-cadherin, with negative hormone receptors status and no HER-2 overexpression. The final staging after chemotherapy was pT3N1M0, necessitating an adjuvant radiotherapy. Four months postoperatively, a CT-scan revealed liver and lung metastases and chemotherapy combining gemcitabine, oxaliplatin and bevacizumab was started for 13 days when she suddenly developed severe abdominal pain. A CT-scan showed a pneumoperitoneum. She had a median laparotomy confirming the diagnosis of peritonitis by digestive perforation without ovarian, uterine, lymphatic, or peritoneal carcinomatosis. Assessment of the totality of the gastrointestinal tract showed two distinct punched out perforations of the small bowel, without macroscopic signs of tumor or metastases: one on the jejunum at 50 cm from the Treitz and the second at 10 cm of the end of the ileum. Small bowel resection with jejunojejunostomy and a lateral ileostomy were performed. Regarding the macroscopical pathological findings, the mucosa showed an ulceration measuring of 1 cm without tumor. On microscopy we found a tranparietal neoplastic infiltration. Vessels were morphologically normal with tumoral cells' morphology and architecture identical to the primary breast carcinoma. Chemotherapy was not reintroduced after surgery and the patient died on the 57th postoperative day.