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.

Solute carrier family 2 member 1 is involved in the development of nonalcoholic fatty liver disease.

UNLABELLED: Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of the present study was to identify genetic variants that could help to prognose and further understand the genetics and development of NAFLD. Allele frequencies of 3,072 single-nucleotide polymorphisms (SNPs) in 92 genes were characterized in 69 NAFLD patients and 217 healthy individuals. The markers that showed significant allele-frequency differences in the pilot groups were subsequently studied in 451 NAFLD patients and 304 healthy controls. Besides this, 4,414 type 2 diabetes mellitus (T2DM) cases and 4,567 controls were genotyped. Liver expression of the associated gene was measured and the effect of its potential role was studied by silencing the gene in vitro. Whole genome expression, oxidative stress (OS), and the consequences of oleic acid (OA)-enriched medium on lipid accumulation in siSLC2A1-THLE2 cells were studied by gene-expression analysis, dihydroethidium staining, BODIPY, and quantification of intracellular triglyceride content, respectively. Several SNPs of SLC2A1 (solute carrier family 2 [facilitated glucose transporter] member 1) showed association with NAFLD, but not with T2DM, being the haplotype containing the minor allele of SLC2A1 sequence related to the susceptibility to develop NAFLD. Gene-expression analysis demonstrated a significant down-regulation of SLC2A1 in NAFLD livers. Enrichment functional analyses of transcriptome profiles drove us to demonstrate that in vitro silencing of SLC2A1 induces an increased OS activity and a higher lipid accumulation under OA treatment. CONCLUSIONS: Genetic variants of SLC2A1 are associated with NAFLD, and in vitro down-regulation of this gene promotes lipid accumulation. Moreover, the oxidative response detected in siSLC2A1-THLE2 cells corroborated the antioxidant properties previously related to this gene and linked the most representative clinical characteristics of NAFLD patients: oxidative injury and increased lipid storage.

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.

CD14dimCD16+ and CD14+CD16+ monocytes in obesity and during weight loss: relationships with fat mass and subclinical atherosclerosis.

OBJECTIVE: Studies suggest the implication of CD16(+) subpopulations (CD14(+)CD16(+), CD14(dim)CD16(+)) in inflammatory diseases. We aimed to determine the frequency of these subpopulations during weight loss in obesity and diabetes, conditions associated with changes in systemic inflammation, and we tested the link with subclinical atherosclerosis. METHODS AND RESULTS: CD14(dim)CD16(+) and CD14(+)CD16(+) frequencies were measured by flow cytometry in lean subjects, obese subjects before and after a hypocaloric diet or gastric surgery, and obese diabetic subjects before and after gastric surgery. Both monocyte subsets were increased in obese subjects, with a significant enrichment of the CD14(dim)CD16(+) subpopulation in obese diabetic patients. Multivariate analysis demonstrated a link between the percentages of CD14(dim)CD16(+) monocytes and glycemia, independent of fat mass. Drastic weight loss led to a sharp decrease of this subset, the variations of which were strongly related to fat mass changes. A reduction of at least 5% of fat mass was sufficient to observe a significant decrease of CD14(dim)CD16(+) monocytes. A diminution of the CD14(+)CD16(+) subset was also observed during weight loss and was associated with a decrease in intima-media thickness. CONCLUSIONS: This work demonstrates a major impact of fat mass variations on CD14(dim)CD16(+) monocyte subsets and that the decrease in the CD14(+)CD16(+) subpopulation is linked to a reduction of subclinical atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00476658.

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.

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.

Liquid chromatography-mass spectrometry-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in most western countries. Current NAFLD diagnosis methods (e.g., liver biopsy analysis or imaging techniques) are poorly suited as tests for such a prevalent condition, from both a clinical and financial point of view. The present work aims to demonstrate the potential utility of serum metabolic profiling in defining phenotypic biomarkers that could be useful in NAFLD management. A parallel animal model/human NAFLD exploratory metabolomics approach was employed, using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) to analyze 42 serum samples collected from nondiabetic, morbidly obese, biopsy-proven NAFLD patients, and 17 animals belonging to the glycine N-methyltransferase knockout (GNMT-KO) NAFLD mouse model. Multivariate statistical analysis of the data revealed a series of common biomarkers that were significantly altered in the NAFLD (GNMT-KO) subjects in comparison to their normal liver counterparts (WT). Many of the compounds observed could be associated with biochemical perturbations associated with liver dysfunction (e.g., reduced Creatine) and inflammation (e.g., eicosanoid signaling). This differential metabolic phenotyping approach may have a future role as a supplement for clinical decision making in NAFLD and in the adaption to more individualized treatment protocols.

Late morbidity after colon interposition for corrosive esophageal injury: risk factors, management, and outcome. A 20-years experience.

OBJECTIVE: The aim of this study was to report our experience in the management of late morbidity after colonic interposition for caustic injury and to assess the influence of coloplasty dysfunction on patient outcome. SUMMARY BACKGROUND DATA: Reports on coloplasty dysfunction after colon interposition for corrosive esophageal injuries are scarce in the literature. Dysfunction of the colonic substitute might jeopardize an already fragile functional result, and appropriate management can improve outcome. METHODS: Long-term follow-up (>6 months) was conducted in 223 patients (125 men; median age, 35 years) who underwent colonic interposition for caustic injuries between 1987 and 2006. Statistical tests were performed on this cohort to identify risk factors for late morbidity and functional outcome. During the same period, 28 patients who underwent colon interposition for caustic injury in another center were referred for treatment of coloplasty dysfunction. Data from these patients were used together with those of our patients to describe specific coloplasty-related complications and their management. RESULTS: With a median follow-up of 5 years (range: 6 months-20 years), late complications were recorded in 125 (55%) of our patients (stenosis 36%, reflux 11%, redundancy 5%). A delay in reconstruction <6 months (P = 0.03) and absence of thoracic inlet enlargement (P = 0.002) were independent predictive factors for cervical anastomotic stenosis. Functional failure was recorded in 52 patients (23%) and was associated with a delay in reconstruction <6 months (P = 0.009) and emergency tracheotomy (P = 0.002). Coloplasty dysfunction was responsible for half of the recorded failures. Revision surgery for coloplasty dysfunction was performed in 96 patients (68 local, 28 referred) with an overall 70% success rate. CONCLUSIONS: Late complications occurred in half of the patients after colonic interposition for corrosive injuries and accounted for half of the functional failures. Prolonged surgical follow-up and appropriate management of coloplasty dysfunction are key factors for long-term success after esophageal reconstruction for caustic injuries.

Use of sealants in pancreatic surgery: critical appraisal of the literature.

BACKGROUND/AIMS: Fibrin sealants containing both fibrin and thrombin have been used to control bleeding, reinforce suture lines and enhance tissue healing. However, the literature provides contradictory results. METHODS: A systematic literature search was performed to determine the use of fibrin sealants in pancreatic surgery. These articles were then critically appraised according to their methodologies, outcomes and conclusions. RESULTS: Twenty-four studies were found, including 6 controlled randomized trials. Of these, 16 studies were analyzed. Many methodological flaws and lack of consistency in definitions were found, making comparisons between studies difficult if not impossible. CONCLUSION: Because of the heterogeneity and lack of high-level evidence, the current literature does not allow us any conclusion: neither is there proof that fibrin sealants are of any real utility in pancreatic surgery, nor that they do not work. Further large-scale controlled trials are necessary before concluding that they do or do not provide any advantages in pancreatic surgery.

Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers.

The RAS-MAPK, PI (3)K signaling pathways form a network that play a central role in tumorigenesis. The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth. We evaluated the clinicopathological features and the prognosis of patients with activated-network colon cancers in a population-based study. A total of 586 colon adenocarcinomas were evaluated using sequencing for mutations of KRAS and PI3KCA, and allelic discrimination for mutation of BRAF. Clinicopathological characteristics were correlated to the risk of bearing a mutation of the network using logistic regression. Three-year survival rates were compared with the Log rank test. A multivariate survival analysis using the Cox model was performed. After adjustment for age and microsatellite instability, activation of the network by mutation of at least 1 of the 3 genes was significantly associated with female sex (p = 0.02) and proximal location (p < 0.001). Lower levels of 3-year survival were associated with activation of the network by mutation of at least 1 of the 3 genes (59.4 and 69.4%, respectively; p = 0.009). These results remained significant in a multivariate analysis adjusted for sex, age, location, stage and microsatellite instability (HR = 1.48; CI CI(95%) = [1.07-2.04]). Our study is the first report to underline the potential role of RAS-MAPK, PI (3)K network mutations on survival in colon cancers. Because of the role of this signaling network on anticancer agents, the evaluation of its mutations could have clinical implications.

[Gallbladder complications after bariatric surgery]. / Complications vésiculaires après chirurgie bariatrique.

With the increased incidence of obesity in the developed countries, and the failure of medical treatments, bariatric surgery has increased rapidly. Although laparoscopic gastroplasty is the most popular bariatric intervention in France, the gold standard tends to be the laparoscopic gastric bypass. The severe weight loss caused by this type of procedure induces specific middle or long term complications such as biliary lithiasis. In this literature we describe different physiopathological mechanisms of lithiasis after gastric bypass by coeliosurgery or gastroplasty, their diagnosis, and preventive treatment to avoid these complications.

Absence of mutation in the putative tumor-suppressor gene KLF6 in colorectal cancers.

The KLF6 gene encodes the Krüppel-like factor 6, a transcription factor that has been individualized as a tumor-suppressor gene involved in the regulation of cell proliferation and differentiation. Recently, high frequency (42%) of KLF6 mutations have been reported in colorectal cancers (CRC) as in prostate cancers, astrocytic gliomas and hepatocellular carcinomas. The aims of the study was to confirm the frequency of KLF6 mutations in a larger series of CRC than that previously published by using DNA extracted from frozen tissue samples, which have been proved to generate less mutational artefact than that extracted from formalin-fixed paraffin-embedded tissue samples, in order to compare KLF6 mutation frequency with that of other common genetic alterations and to determine genotype-phenotype correlations. Amplification and direct sequencing of KLF6 exon 2 of 76 CRC and matched normal frozen tissues was performed. Polymorphisms were observed in 14 cases, among which two (T35T and S116S) had not already been reported. No KLF6 somatic mutation was observed. Our data suggest a minor role of KLF6 mutation in colorectal carcinogenesis and underline the fact that the validity of sequence informations obtained from DNA extracted from formalin-fixed tissues may be limited.

Endothelial cells from visceral adipose tissue disrupt adipocyte functions in a three-dimensional setting: partial rescue by angiopoietin-1.

During obesity, chronic inflammation of human white adipose tissue (WAT) is associated with metabolic and vascular alterations. Endothelial cells from visceral WAT (VAT-ECs) exhibit a proinflammatory and senescent phenotype and could alter adipocyte functions. We aimed to determine the contribution of VAT-ECs to adipocyte dysfunction related to inflammation and to rescue these alterations by anti-inflammatory strategies. We developed an original three-dimensional setting allowing maintenance of unilocular adipocyte functions. Coculture experiments demonstrated that VAT-ECs provoked a decrease in the lipolytic activity, adipokine secretion, and insulin sensitivity of adipocytes from obese subjects, as well as an increased production of several inflammatory molecules. Interleukin (IL)-6 and IL-1ß were identified as potential actors in these adipocyte alterations. The inflammatory burst was not observed in cocultured cells from lean subjects. Interestingly, pericytes, in functional interactions with ECs, exhibited a proinflammatory phenotype with diminished angiopoietin-1 (Ang-1) secretion in WAT from obese subjects. Using the anti-inflammatory Ang-1, we corrected some deleterious effects of WAT-ECs on adipocytes, improving lipolytic activity and insulin sensitivity and reducing the secretion of proinflammatory molecules. In conclusion, we identified a negative impact of VAT-ECs on adipocyte functions during human obesity. Therapeutic options targeting EC inflammation could prevent adipocyte alterations that contribute to obesity comorbidities.

Similar postoperative safety between primary and revisional gastric bypass for failed gastric banding.

IMPORTANCE: Adjustable gastric bands are widely used because of low postoperative morbidity, but their long-term results are poor, often leading to revisional surgery. OBJECTIVE: To assess the safety of revisional procedures by comparing the 30-day outcomes of primary gastric bypass vs revisions following failed adjustable gastric banding. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review using logistic regression models to compute odds ratios (95% CIs) across preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) quartiles to evaluate the risk for major adverse outcomes at 30 days (death, venous thromboembolism, reinterventions, and failure to be discharged). The prospective database of a single university surgical center in Paris, France, was queried for clinical and other relevant data among all patients undergoing primary or revisional laparoscopic gastric bypass between January 1, 2004, and June 30, 2013. MAIN OUTCOMES AND MEASURES: The primary outcome was a comparison between 30-day outcomes of primary gastric bypass and procedures following failed adjustable gastric banding. RESULTS: In total, 831 patients had a primary procedure (group 1), and 177 patients had a secondary procedure after failed adjustable gastric banding (group 2). Overall, 78.7% of patients were female, the mean (SD) patient age was 42.6 (11.6) years, the mean (SD) body mass index was 47.6 (7.6), and mortality at 30 days was 0.5%. The rates of major adverse outcomes were similar in group 1 (7.8%) and group 2 (8.5%) (P = .77). In multivariate analyses, odds ratios for major adverse outcomes across preoperative body mass index quartiles (<42, 42-46, >46 to 52, and >52) were 1.00, 0.39 (95% CI, 0.20-0.77; P = .006), 0.55 (95% CI, 0.30-1.02; P = .06), and 0.50 (95% CI, 0.27-0.94; P = .03), respectively. CONCLUSIONS AND RELEVANCE: The 30-day major adverse outcome rates were similar for primary gastric bypass and for procedures following failed adjustable gastric banding. Long-term comparative studies are required to better understand the quadratic relationship between body mass index and early postoperative outcomes.

SMRT-GPS2 corepressor pathway dysregulation coincides with obesity-linked adipocyte inflammation.

Low-grade chronic inflammation is a major characteristic of obesity and results from deregulated white adipose tissue function. Consequently, there is interest in identifying the underlying regulatory mechanisms and components that drive adipocyte inflammation. Here, we report that expression of the transcriptional corepressor complex subunits GPS2 and SMRT was significantly reduced in obese adipose tissue, inversely correlated to inflammatory status, and was restored upon gastric bypass surgery-induced weight loss in morbid obesity. These alterations correlated with reduced occupancy of the corepressor complex at inflammatory promoters, providing a mechanistic explanation for elevated inflammatory transcription. In support of these correlations, RNAi-mediated depletion of GPS2 and SMRT from cultured human adipocytes promoted derepression of inflammatory transcription and elevation of obesity-associated inflammatory markers, such as IL-6 and MCP-1. Furthermore, we identified a regulatory cascade containing PPARγ and TWIST1 that controlled the expression of GPS2 and SMRT in human adipocytes. These findings were clinically relevant, because treatment of diabetic obese patients with pioglitazone, an antidiabetic and antiinflammatory PPARγ agonist, restored expression of TWIST1, GPS2, and SMRT in adipose tissue. Collectively, our findings identify alterations in a regulatory transcriptional network in adipocytes involving the dysregulation of a specific corepressor complex as among the initiating events promoting adipose tissue inflammation in human obesity.

Clinical review: Bariatric surgery following treatment for craniopharyngioma: a systematic review and individual-level data meta-analysis.

OBJECTIVES: Craniopharyngiomas are rare low-grade tumors located in the hypothalamic and/or pituitary region. Hypothalamic involvement and treatment resulting in hypothalamic damage are known to lead to development of "hypothalamic obesity" (HyOb) in 50% of cases. The management of HyOb, associated with eating disorders and rapid comorbidities, is an important issue. Bariatric surgery is the most effective therapy for weight loss in patients with severe exogenous obesity. The aim of this systematic review and meta-analysis was to determine the 12-month outcome of bariatric surgery for HyOb due to craniopharyngioma treatment. METHODS AND RESULTS: Relevant studies were identified by searches of the MEDLINE and EMBASE databases until January 2013. A total of 21 cases were included: 6 with adjustable gastric banding, 8 with sleeve gastrectomy, 6 with Roux-en-Y gastric bypass, and 1 with biliopancreatic diversion. After data pooling, mean weight difference was -20.9 kg after 6 months (95% confidence interval [CI], -35.4, -6.3) and -15.1 kg after 12 months (95% CI, -31.7, +1.4). The maximal mean weight loss was achieved by the gastric bypass group: -31.0 kg (95% CI, -77.5, +15.5) and -33.7 kg (95% CI, -80.7, +13.3) after 6 and 12 months, respectively. CONCLUSIONS: In this largest ever published study on the effect of bariatric surgery on obesity after craniopharyngioma treatment, we observed an important weight loss after 1 year of follow-up. Larger studies are warranted to establish appropriate selection criteria and the best surgical technique to perform bariatric surgery.