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.

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.

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.

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.

Noninvasive diagnosis of nonalcoholic steatohepatitis disease based on clinical decision support system.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic disease associated with metabolic syndrome. NAFLD covers a spectrum of liver disease from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NASH is a disease evolving under the influence of various stimuli still poorly understood. In this paper we present new clinical decision support system (CDSS) for the diagnosis of NASH and the comparison of this system with machine learning algorithms.

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.

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.

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.

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.

Complicated diverticular disease: the changing paradigm for treatment.

The term "complicated" diverticulitis is reserved for inflamed diverticular disease complicated by bleeding, abscess, peritonitis, fistula or bowel obstruction. Hemorrhage is best treated by angioembolization (interventional radiology). Treatment of infected diverticulitis has evolved enormously thanks to: 1) laparoscopic colonic resection followed or not (Hartmann's procedure) by restoration of intestinal continuity, 2) simple laparoscopic lavage (for peritonitis +/- resection). Diverticulitis (inflammation) may be treated with antibiotics alone, anti-inflammatory drugs, combined with bed rest and hygienic measures. Diverticular abscesses (Hinchey Grades I, II) may be initially treated by antibiotics alone and/or percutaneous drainage, depending on the size of the abscess. Generalized purulent peritonitis (Hinchey III) may be treated by the classic Hartmann procedure, or exteriorization of the perforation as a stoma, primary resection with or without anastomosis, with or without diversion, and last, simple laparoscopic lavage, usually even without drainage. Feculent peritonitis (Hinchey IV), a traditional indication for Hartmann's procedure, may also benefit from primary resection followed by anastomosis, with or without diversion, and even laparoscopic lavage. Acute obstruction (nearby inflammation, or adhesions, pseudotumoral formation, chronic strictures) and fistula are most often treated by resection, ideally laparoscopic. Minimal invasive therapeutic algorithms that, combined with less strict indications for radical surgery before a definite recurrence pattern is established, has definitely lead to fewer resections and/or stomas, reducing their attendant morbidity and mortality, improved post-interventional quality of life, and less costly therapeutic policies.

Complicated diverticular disease: the changing paradigm for treatment / Doença diverticular complicada: alterando o padrão de tratamento

The term "complicated" diverticulitis is reserved for inflamed diverticular disease complicated by bleeding, abscess, peritonitis, fistula or bowel obstruction. Hemorrhage is best treated by angioembolization (interventional radiology). Treatment of infected diverticulitis has evolved enormously thanks to: 1) laparoscopic colonic resection followed or not (Hartmann's procedure) by restoration of intestinal continuity, 2) simple laparoscopic lavage (for peritonitis +/- resection). Diverticulitis (inflammation) may be treated with antibiotics alone, anti-inflammatory drugs, combined with bed rest and hygienic measures. Diverticular abscesses (Hinchey Grades I, II) may be initially treated by antibiotics alone and/or percutaneous drainage, depending on the size of the abscess. Generalized purulent peritonitis (Hinchey III) may be treated by the classic Hartmann procedure, or exteriorization of the perforation as a stoma, primary resection with or without anastomosis, with or without diversion, and last, simple laparoscopic lavage, usually even without drainage. Feculent peritonitis (Hinchey IV), a traditional indication for Hartmann's procedure, may also benefit from primary resection followed by anastomosis, with or without diversion, and even laparoscopic lavage. Acute obstruction (nearby inflammation, or adhesions, pseudotumoral formation, chronic strictures) and fistula are most often treated by resection, ideally laparoscopic. Minimal invasive therapeutic algorithms that, combined with less strict indications for radical surgery before a definite recurrence pattern is established, has definitely lead to fewer resections and/or stomas, reducing their attendant morbidity and mortality, improved post-interventional quality of life, and less costly therapeutic policies.

O termo diverticulite "complicada" é reservado para a doença diverticular complicada por sangramento, abscesso, peritonite, fístula ou obstrução intestinal. A hemorragia é melhor tratada por angioembolização (radiologia intervencionista). O tratamento de diverticulite infectada evoluiu enormemente graças a: 1) ressecção laparoscópica do cólon seguida ou não (procedimento de Hartmann) pelo restabelecimento de continuidade intestinal, 2) lavado laparoscópico simples (peritonite + / - ressecção). A diverticulite (inflamação) pode ser tratada somente com antibióticos, anti-inflamatórios, combinados com repouso e medidas de higiene. O abscesso diverticular (Hinchey graus I, II) pode ser inicialmente tratado somente com antibióticos e / ou drenagem percutânea, dependendo do tamanho do abcesso. A peritonite purulenta generalizada (Hinchey III) pode ser tratada pelo clássico procedimento Hartmann, pela exteriorização da perfuração, como se fosse um estoma, pela ressecção primária com ou sem anastomose, com ou sem desvio do trânsito e, por último, a simples lavagem laparoscópica, geralmente, sem drenagem. A peritonite por fezes (Hinchey IV), uma indicação para o tradicional procedimento de Hartmann, também pode se beneficiar da ressecção primária seguida de anastomose, com ou sem desvio e lavagem laparoscópica. A obstrução aguda (inflamação local, ou aderências, formação pseudotumoral, estenoses crônicas) e fístula são, na maioria das vezes, tratadas por ressecção, preferencialmente, laparoscópica. Algoritmos terapêuticos pouco invasivos combinadas com indicações menos rigorosas para a o emprego da cirurgia radical antes de um padrão definido de recorrência, estão estabelecidos, ocasionando um número menor de ressecções e / ou estomas, reduzindo a morbidade e a mortalidade, melhorando a qualidade de vida após a intervenção, e geram uma tratamento menos dispendioso.

Mast cells in human adipose tissue: link with morbid obesity, inflammatory status, and diabetes.

AIMS AND HYPOTHESIS: Mast cells are immune cells known for their role in several inflammatory and fibrotic diseases. Recent works in mice suggest that mast cells could be cellular actors involved in the pathophysiology of obesity, a disease characterized by white adipose tissue (WAT) and systemic inflammation. The aim of the study was to better characterize mast cells in WAT of obese with or without type 2 diabetes and lean subjects as well as to explore the relationship with WAT inflammation and fibrosis. METHODS: Subcutaneous and omental adipose tissue from six lean subjects, 10 obese nondiabetic, and 10 diabetic patients was analyzed by immunohistochemistry and real-time PCR for inflammatory and fibrosis markers. Cytokines secretion of mast cells isolated from WAT and cultured in different conditions was estimated by cytokine array kit. RESULTS: We found that mast cells are activated in human adipose tissue and localized preferentially in fibrosis depots, a local condition that stimulates their inflammatory state. Mast cells with tryptase(+) chymase(+) staining tended to be higher in obese omental adipose tissue. We found positive links between mast cell number and several characteristics of obese WAT including fibrosis, macrophage accumulation, and endothelial cell inflammation. Mast cell number and their inflammatory phenotype are associated with diabetes parameters. CONCLUSION AND INTERPRETATION: Mast cells are cellular actors of WAT inflammation and possibly fibrotic state found in obesity and diabetes. Whether mast cells could be involved in the pathophysiology of diabetes needs additional study as well as the positioning of these cells in driving pathological alterations of WAT in these chronic metabolic diseases.

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.

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.

GLUT2 accumulation in enterocyte apical and intracellular membranes: a study in morbidly obese human subjects and ob/ob and high fat-fed mice.

OBJECTIVE: In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance. RESEARCH DESIGN AND METHODS: Subcellular location of GLUT2 in jejunal enterocytes was analyzed by confocal and electron microscopy imaging and Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral metformin or in high-fat low-carbohydrate diet-fed C57Bl/6 mice. Glucose absorption and secretion were respectively estimated by oral glucose tolerance test and secretion of [U-(14)C]-3-O-methyl glucose into lumen. RESULTS: In human enterocytes, GLUT2 was consistently located in basolateral membranes. Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia. In addition, intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose release into intestinal lumen. CONCLUSIONS: In morbidly obese insulin-resistant subjects, GLUT2 was accumulated in apical and/or endosomal membranes of enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes are a sign of intestinal adaptations to human metabolic pathology.

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.

[Education and teaching laparoscopic surgery in Europe: present constraints and role of the European Association for Endoscopic Surgery.]

As we move on to the second decade of the 21st century, many changes in education and, particularly, in training future surgeons, have come to pass. Several of these changes are the result of a natural evolution in teaching methods, but others have been dictated by global modifications in the educational and social systems reigning throughout the Western culture. The recent evolution to less aggressive therapy and, in particular, surgical techniques, attests to the desire to decrease patient harm. Laparoscopic surgery, based on less invasive parietal violation and insult, responding to the above-mentioned concerns, has rekindled the debate on patient safety but also has opened the debate on how to best teach the technique. This paper endeavors to describe the problems created by the social and economic changes in the last few decades, to assess the consequences on teaching and learning laparoscopic surgery for the surgeon and to review possible solutions.

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.