Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice.

Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.

The Four Different Types of Internal Hernia Occurring After Laparascopic Roux-en-Y Gastric Bypass Performed for Morbid Obesity: Are There Any Multidetector Computed Tomography (MDCT) Features Permitting Their Distinction?

BACKGROUND: Four different types of internal hernias (IH) are known to occur after laparoscopic Roux-en-Y gastric bypass (LRYGBP) performed for morbid obesity. We evaluate multidetector row helical computed tomography (MDCT) features for their differentiation. METHODS: From a prospectively collected database including 349 patients with LRYGBP, 34 acutely symptomatic patients (28 women, mean age 32.6), operated on for IH immediately after undergoing MDCT, were selected. Surgery confirmed 4 (11.6%) patients with transmesocolic, 10 (29.4%) with Petersen's, 15 (44.2%) with mesojejunal, and 5 (14.8%) with jejunojejunal IH. In consensus, 2 radiologists analyzed 13 MDCT features to distinguish the four types of IH. Statistical significance was calculated (p < 0.05, Fisher's exact test, chi-square test). RESULTS: MDCT features of small bowel obstruction (SBO) (n = 25, 73.5%), volvulus (n = 22, 64.7%), or a cluster of small bowel loops (SBL) (n = 27, 79.4%) were inconsistently present and overlapped between the four IH. The following features allowed for IH differentiation: left upper quadrant clustered small bowel loops (p < 0.0001) and a mesocolic hernial orifice (p = 0.0003) suggested transmesocolic IH. SBL abutting onto the left abdominal wall (p = 0.0021) and left abdominal shift of the superior mesenteric vessels (SMV) (p = 0.0045) suggested Petersen's hernia. The SMV predominantly shifted towards the right anterior abdominal wall in mesojejunal hernia (p = 0.0033). Location of the hernial orifice near the distal anastomosis (p = 0.0431) and jejunojejunal suture widening (p = 0.0005) indicated jejunojejunal hernia. CONCLUSIONS: None of the four IH seems associated with a higher risk of SBO. Certain MDCT features, such as the position of clustered SBL and hernial orifice, help distinguish between the four IH and may permit straightforward surgery.

Gastric outlet obstruction by Brunner's gland hyperplasia in an 8-year-old child.

Several cases of Brunner's gland hyperplasia causing hemorrhage, obstruction, or intussusception have been published in the adult literature. Similar cases in the pediatric population are very rare and have only been described twice, always associated with chronic renal failure. We report the third and youngest case of gastric outlet obstruction because of Brunner's gland hyperplasia focusing on histopathologic condition and treatment based on a review of the literature.

In vitro assessment of the pulmonary toxicity and gastric availability of lead-rich particles from a lead recycling plant

Epidemiological studies in urban areas have linked increasing respiratory and cardiovascular pathologies with atmospheric particulate matter (PM) from anthropic activities. However, the biological fate of metal-rich PM industrial emissions in urban areas of developed countries remains understudied. Lead toxicity and bioaccessibility assessments were therefore performed on emissions from a lead recycling plant, using complementary chemical acellular tests and toxicological assays, as a function of PM size (PM(10-2.5), PM(2.5-1) and PM(1)) and origin (furnace, refining and channeled emissions). Process PM displayed differences in metal content, granulometry, and percentage of inhalable fraction as a function of their origin. Lead gastric bioaccessibility was relatively low (maximum 25%) versus previous studies; although, because of high total lead concentrations, significant metal quantities were solubilized in simulated gastrointestinal fluids. Regardless of origin, the finest PM(1) particles induced the most significant pro-inflammatory response in human bronchial epithelial cells. Moreover, this biological response correlated with pro-oxidant potential assay results, suggesting some biological predictive value for acellular tests. Pulmonary effects from lead-rich PM could be driven by thiol complexation with either lead ions or directly on the particulate surface. Finally, health concern of PM was discussed on the basis of pro-inflammatory effects, accellular test results, and PM size distribution.

Roux-en-Y gastric bypass vs gastric banding for morbid obesity: a case-matched study of 442 patients.

HYPOTHESIS: Gastric banding (GB) and Roux-en-Y gastric bypass (RYGBP) are used in the treatment of morbidly obese patients. We hypothesized that RYGBP provides superior results. DESIGN: Matched-pair study in patients with a body mass index (BMI) less than 50. SETTING: University hospital and regional community hospital with a common bariatric surgeon. PATIENTS: Four hundred forty-two patients were matched according to sex, age, and BMI. INTERVENTIONS: Laparoscopic GB or RYGBP. MAIN OUTCOME MEASURES: Operative morbidity, weight loss, residual BMI, quality of life, food tolerance, lipid profile, and long-term morbidity. RESULTS: Follow-up was 92.3% at the end of the study period (6 years postoperatively). Early morbidity was higher after RYGBP than after GB (17.2% vs 5.4%; P<.001), but major morbidity was similar. Weight loss was quicker, maximal weight loss was greater, and weight loss remained significantly better after RYGBP until the sixth postoperative year. At 6 years, there were more failures (BMI>35 or reversal of the procedure/conversion) after GB (48.3% vs 12.3%; P<.001). There were more long-term complications (41.6% vs 19%; P.001) and more reoperations (26.7% vs 12.7%; P<.001) after GB. Comorbidities improved more after RYGBP. CONCLUSIONS: Roux-en-Y gastric bypass is associated with better weight loss, resulting in a better correction of some comorbidities than GB, at the price of a higher early complication rate. This difference, however, is largely compensated by the much higher long-term complication and reoperation rates seen after GB.

Laparoscopic gastric banding: a prospective, randomized study comparing the Lapband and the SAGB: early results.

OBJECTIVE: The objective of this study was to evaluate the results of laparoscopic gastric banding using 2 different bands (the Lapband [Bioenterics, Carpinteria, CA] and the SAGB [Swedish Adjustable Gastric Band; Obtech Medical, 6310 Zug, Switzerland]) in terms of weight loss and correction of comorbidities, short-and long-term complications, and improvement of quality of life in morbidly obese patients SUMMARY BACKGROUND DATA: During the past 10 years, gastric banding has become 1 of the most common bariatric procedures, at least in Europe and Australia. Weight loss can be excellent, but it is not sufficient in a significant proportion of patients, and a number of long-term complications can develop. We hypothesized that the type of band could be of importance in the outcome. METHODS: One hundred eighty morbidly obese patients were randomly assigned to receive the Lapband or the SAGB. All the procedures were performed by the same surgeon. The primary end point was weight loss, and secondary end points were correction of comorbidities, early- and long-term complications, importance of food restriction, and improvement of quality of life. RESULTS: Initial weight loss was faster in the Lapband group, but weight loss was eventually identical in the 2 groups. There was a trend toward more early band-related complications and more band infections with the SAGB, but the study had limited power in that respect. Correction of comorbidities, food restriction, long-term complications, and improvement of quality of life were identical. Only 55% to 60% of the patients achieved an excess weight loss of at least 50% in both groups. There was no difference in the incidence of long-term complications. CONCLUSIONS: Gastric banding can be performed safely with the Lapband or the SAGB with similar short- and midterm results with respect to weight loss and morbidity. Only 50% to 60% of the patients will achieve sufficient weight loss, and close to 10% at least will develop severe long-term complications.

A new type of internal hernia after laparoscopic Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGBP) is currently the most common bariatric procedure. One of its late complications is the development of internal hernia, which can lead to acute intestinal obstruction or recurrent colicky abdominal pain. The aim of this paper is to present a new, unusual, and so far not reported type of internal hernia. A common computerized database is maintained for all patients undergoing bariatric surgery in our departments. The charts of patients with the diagnosis of internal hernia were reviewed. Three patients were identified who developed acute intestinal obstruction due to an internal hernia located between the jejunojejunostomy and the end of the biliopancreatic limb, directly between two jejunal limbs with no mesentery involved. Another seven patients with intermittent colicky abdominal pain, re-explored for the suspicion of internal hernia, were found to also have an open window of the same location apart from a hernia at one of the typical hernia sites. Since this gap is systematically closed during RYGBP, no other patient has been observed with this problem. Even very small defects can lead to the development of internal hernias after RYGBP. Patients with suggestive symptoms must be explored. Closure of the jejunojejunal defect with nonabsorbable sutures prevents the development of an internal hernia between the jejunal loops at the jejunojejunostomy.

Laparoscopic Roux-en-Y Gastric Bypass After Failed Vertical Banded Gastroplasty: a Multicenter Experience with 203 Patients.

BACKGROUND: Vertical banded gastroplasty (VBG) has long been the main restrictive procedure for morbid obesity but has many long-term complications for which conversion to Roux-en-Y gastric bypass (RYGBP) is often considered the best option. METHODS: This series regroups patients operated on by three different surgeons in four different centers. All data were collected prospectively, then pooled and analyzed retrospectively. RESULTS: Out of 2,522 RYGBP performed between 1998 and 2010, 538 were reoperations, including 203 laparoscopic RYGBP after VBG. There were 175 women and 28 men. The mean BMI before VBG was 43.2 ± 6.3, and the mean BMI before reoperation was 37.4 ± 8.3. Most patients had more than one indication for reoperation and/or had regained significant weight. There was no conversion to open surgery. A total of 24 patients (11.8 %) developed complications, including nine (4.5 %) who required reoperation and one death. With a follow-up of 88.9 % after 8 years, the mean BMI after 1, 3, 5, 7, and 9 years was 29.1, 28.8, 28.7, 29.9, and 28.8, respectively. CONCLUSIONS: On the basis of this experience, the largest with laparoscopic reoperative RYGBP after failed VBG, we conclude that this procedure can safely be performed in experienced hands, with weight loss results similar to those observed after primary RYGBP. In patients with too difficult an anatomy below the cardia, dividing the esophagus just above the esophago-gastric junction and performing an esophagojejunostomy may be a safe alternative to converting to a Scopinaro-type BPD, obviating the additional long-term risks associated with malabsorption.

Almost routine prophylactic cholecystectomy during laparoscopic gastric bypass is safe

RAPPORT DE SYNTHESE : Introduction : les patients obèses morbides présentent un risque majeur de développer des calculs biliaires en raison d'une sécrétion accrue de cholestérol dans la bile. Ce risque, davantage élevé dans la phase de perte pondérale rapide consécutive à la chirurgie bariatrique ou lors de régimes amaigrissants, est souvent la cause de nombreux symptômes, voire de complications biliaires. Aussi l'association d'une cholécystectomie à la chirurgie bariatrique, notamment le bypass gastrique laparoscopique a-t-elle été proposée afin d'éviter ces complications parfois redoutables dans cette population fragile. Ce concept a cependant fait l'objet de démentis dans de récentes études où ce risque apparaîtrait moins élevé, et la cholécystectomie durant le by- pris gastrique laparoscopique pourrait être grevée de difficultés et présenter des risques opératoires non négligeables pour le patient. Patients et méthodes : notre série comporte 772 patients opérés entre 2000 et 2007 par by-pass gastrique laparoscopique, avec montage d'une anse en Y selon Roux. Ces patients obèses morbides avaient été sélectionnés sur la base d'une anamnèse concluante, d'un examen anthropométrique, d'un bilan sanguin et d'un ultrason abdominal. Une analyse rétrospective des résultats d'ultrason abdominal préopératoire et des rapports histopathologiques des vésicules biliaires en postopératoire a été réalisée chez les patients opérés avant 2004. Résultats : 58 patients (7,5 %) avaient déjà eu une cholécystectomie. L'US abdominal a révélé des calculs ou de la boue biliaire chez 81 patients (11,3 %), un polype chez un patient et une vésicule biliaire normale chez les patients restants. La cholécystectomie a été réalisée concomitamment au by-pass gastrique chez 66S patients (91,7 %) et des calculs biliaires retrouvés à l'examen per-opératoire des vésicules biliaires chez 25 patients (3,9 %), rapportant alors la prévalence de la cholélithiase à 21,2 % dans cette population. L'âge des patients porteurs de calculs biliaires était significativement plus élevé que celui des patients sans calculs biliares (43,5 contre 38,7 ans, P < 0,0001). A l'examen histopathologique, des anomalies ont été décrites dans 81,8 % des vésicules biliaires, consistant pour la plupart en cholécystite chronique et cholestérolose. Aucune complication post-opératoire n'a été associée à la cholécystectomie et le prolongement du temps opératoire était en moyenne de 19 minutes (4 - 45 minutes) sans aucun impact sur le séjour hospitalier. La cholécystectomie n'a pas été réalisée chez 59 patients (8,3 %) en raison de conditions opératoires défavorables, notamment une exposition insuffisante. Un traitement d'acide ursodésoxycholique a été prescrit sur une période de 6 mois et aucun de ces patients n'a manifesté de symptômes biliaires. Conclusion : la cholécystectomie peut être réalisée à titre prophylactique et en toute sécurité au cours du by-pass gastrique laparoscopique. Cet acte opératoire supplémentaire sans conséquence sur le séjour hospitalier, constitue selon la présente étude une forme de prophylaxie recommandable dans la prévention de la formation des calculs biliaires dans la phase de perte pondérale post-opératoire. Sa supériorité ou non par rapport à la prophylaxie médicamenteuse à l'acide ursodésoxycholique n'a pas encore été établie. Des études prospectives randomisées seraient nécessaires afin de confirmer l'avantage de l'une ou l'autre de ces deux alternatives.

De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient.

ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. IMPORTANCE Pneumocystis pneumonia is a major cause of mortality in patients with impaired immune systems. The availability of the P. jirovecii genome sequence allows new analyses to be performed which open avenues to solve critical issues for this deadly human disease. The most important ones are (i) identification of nutritional supplements for development of culture in vitro, which is still lacking 100 years after discovery of the pathogen; (ii) identification of new targets for development of new drugs, given the paucity of present treatments and emerging resistance; and (iii) identification of targets for development of vaccines.

Development of targeted therapies in advanced gastric cancer: promising exploratory steps in a new era.

PURPOSE OF REVIEW: Many chemotherapeutic drugs, including fluoropyrimidines, platinums, CPT-11, taxanes and adriamycin have single-agent activity in advanced gastric cancer. Although combination chemotherapy has been shown to be more effective than single agents, response rates between 30 and 50% have not fulfilled their promise as progression-free survival from the best combinations ranges between 3 and 7 months and overall survival between 8 and 11 months. The development of targeted therapies in gastric cancer clearly stays behind the integration of these novel agents into new treatment concepts for patients with colorectal cancer. This review summarizes the experience and major recent advances in the development of targeted therapies in advanced gastric cancer. RECENT FINDINGS: Recent publications on targeted therapies in gastric cancer are limited to nonrandomized phase I or II trials. The majority of agents tested were angiogenesis inhibitors or agents targeting the epidermal growth factor receptors epidermal growth factor receptor 1 and HER2. SUMMARY: Adequately powered, randomized phase III trials are necessary to define the clinical role of targeted therapies in advanced gastric cancer. Biomarker studies to correlate with treatment outcomes will be critical to identify patients who benefit most from chemotherapy and targeted therapy.