Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

Multipurpose use of the 'bear claw' (over-the-scope-clip system) to treat endoluminal gastrointestinal disorders.

BACKGROUND AND AIM: The 'bear-claw' or over-the-scope-clip system (OTSC; Ovesco Endoscopy, Tübingen, Germany) is a new clipping device developed for closure of large luminal gastrointestinal (GI) defects. The aim of the present study was to evaluate the clinical outcomes of patients treated with the OTSC. METHODS: The present study was an observational, open-label, retrospective, single-arm case series conducted at two hospitals with tertiary care endoscopy. It involved 20 clip applications in 16 patients (median age 65.8 years [range 51-90 years], seven women) with GI defects from fistulas and anastomotic dehiscence and peptic ulcer bleeding. RESULTS: The range of indications included gastrointestinal bleeding (n=6), gastrocutaneous fistulas (n=3), esophagotracheal and/or esophagopleural fistulae (n=3), resection ofsubmucosal tumor (n=2), stent fixation (n=1), and anastomotic leak after esophagectomy (n=1). The overall success rate for the OTSC device was 75% (12 out of 16 patients). The overall per case success rate was 70% (14 of 20 applications). Mean follow up was 10 months (range 1-10). There were no complications (0%) related to endoscopy, sedation or application of the clipping device. CONCLUSIONS: The OTSC system is a useful device in a variety of clinical scenarios including the management of larger GI leaks and fistulas, GI bleeding, full-thickness resection of tumors, and stent anchoring, even in very old and frail patients.

The University of Alabama at Birmingham Surgery Community Network: Tackling the Challenges of Rural Surgery.

Over the past 5 years, The University of Alabama at Birmingham (UAB) Department of Surgery has taken a keen interest in the practice of surgery in rural Alabama and has established the UAB surgery community network. Our goal is to improve the delivery of surgical care in rural areas through active recruitment of rural surgeons, the development of research around rural surgery practice, and the expansion of a surgery network throughout the state. Here, we will present the challenges faced by rural surgery, our early work to address these challenges, and offer a plan for moving forward.

Stromal regulation of human gastric dendritic cells restricts the Th1 response to Helicobacter pylori.

BACKGROUND & AIMS: Mucosal dendritic cells (DCs) play a key role in initiating the T-helper (Th)1 response to Helicobacter pylori. To further elucidate the mucosal response to H pylori, we examined whether gastric stromal factors condition DCs to support tolerance to H pylori, analogous to intestinal stromal factor-driven macrophage tolerance to commensal bacteria. METHODS: To model mucosal DC development, we isolated and cultured cell-depleted human stroma/extracellular matrix from fresh gastric and intestinal mucosa to generate stroma-conditioned media. We then analyzed the capacity of stroma-conditioned media-treated monocyte-derived DCs and primary human gastric and intestinal DCs pulsed in vitro with H pylori to induce T-cell proliferation and interferon gamma secretion. RESULTS: Stromal factors in gastric mucosa suppressed H pylori-stimulated DC activation and the ability of DCs to drive a Th1 proliferative and cytokine response to H pylori. The ability of gastric stromal factors to down-regulate DC function was similar to that of intestinal stromal factors and was independent of transforming growth factor ß, prostaglandin E2, interleukin (IL)-10, and thymic stromal lymphopoietin. Stroma-conditioned media-induced reduction in DC-stimulated Th1 responses was associated with reduced DC release of IL-12. CONCLUSIONS: Gastric stromal factors down-regulate DC responsiveness to H pylori, resulting in a dampened gastric Th1 response. We speculate that stroma-induced down-regulation of DC function contributes to the permissiveness of both gastric and intestinal mucosa to colonization by persistent residential microbes.

Insurance-mandated preoperative diet and outcomes after bariatric surgery.

BACKGROUND: Despite a lack of demonstrated patient benefit, many insurance providers mandate a physician-supervised diet before financial coverage for bariatric surgery. OBJECTIVES: To compare weight loss between patients with versus without insurance mandating a preoperative diet. SETTING: University hospital, United States. METHODS: Retrospective study of all patients who underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy over a 5-year period, stratified based on whether an insurance-mandated physician-supervised diet was required. Weight loss outcomes at 6, 12, and 24 months postoperation were compared. Linear mixed-models and backward-stepwise selection were used. P<0.05 was considered significant. RESULTS: Of 284 patients, 225 (79%) were required and 59 (21%) were not required to complete a preoperative diet by their insurance provider. Patients without the requirement had a shorter time to operation from initial consultation (P = .04), were older (P<.01), and were more likely to have government-sponsored insurance (P<.01). There was no difference in preoperative weight or body mass index or co-morbidities. In unadjusted models, percent excess weight loss was superior in the group without an insurance-mandated diet at 12 (P = .050) and 24 (P = .045) months. In adjusted analyses, this group also had greater percent excess weight loss at 6 (P<.001), 12 (P<.001), and 24 (P<.001) months; percent total weight loss at 24 months (P = .004); and change in body mass index at 6 (P = .032) and 24 (P = .007) months. There was no difference in length of stay or complication rates. CONCLUSIONS: Insurance-mandated preoperative diets delay treatment and may lead to inferior weight loss.

Effectiveness of thoracoscopic truncal vagotomy in the treatment of marginal ulcers after laparoscopic Roux-en-Y gastric bypass.

Marginal ulcer is a significant complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Most marginal ulcers resolve with medical management, but nonhealing ulcers may require revision of the gastrojejunostomy, a procedure with significant morbidity and mortality. Traditionally, surgical therapy for refractory peptic ulcers includes a vagotomy. The current study evaluates the effectiveness of thoracoscopic truncal vagotomy (TTV) in the management of refractory marginal ulcers. All patients at two institutions with an intractable marginal ulcer after LRYGB treated with TTV between 2003 and 2010 were reviewed. Data were collected from chart review and telephone interview. Seventeen patients (mean age, 39 ± 13 years; 16 females) were diagnosed with marginal ulceration a median of 18 months after LRYGB and proceeded to TTV at a mean of 39 ± 43 weeks (range, 1 to 114 weeks) after the diagnosis. The median operative time was 89 ± 65 minutes (range, 45 to 318 minutes). Four patients had a complication (sympathetic contralateral pleural effusion, pneumothorax, operative bleeding, and readmission for emesis). Eleven patients had follow-up of 3 months to 6 years (median, 7 months). Nine patients (82%) had symptomatic improvement and/or endoscopic resolution, whereas two (18%) did not. No patient had endoscopic evidence of persistent or recurrent marginal ulcer. TTV achieves symptomatic improvement and/or endoscopic resolution of intractable marginal ulcers in over 80 per cent of patients status post gastric bypass and therefore offers a less morbid alternative to revision of the gastrojejunostomy.