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BACKGROUND: Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. STUDY DESIGN: This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. RESULTS: The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). CONCLUSIONS: This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.

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OBJECTIVE: To evaluate the impact of MSA on lower esophageal sphincter (LES) and esophageal body using high resolution impedance manometry. BACKGROUND: MSA is an effective treatment in patients with gastroesophageal reflux disease, but there is limited data on its impact on esophageal functional physiology. METHODS: Patients who underwent MSA were approached 1-year after surgery for objective foregut testing consists of upper endoscopy, esophagram, high resolution impedance manometry, and esophageal pH-monitoring. Postoperative data were then compared to the preoperative measurements. RESULTS: A total of 100 patients were included in this study. At a mean follow up of 14.9(10.1) months, 72% had normalization of esophageal acid exposure. MSA resulted in an increase in mean LES resting pressure [29.3(12.9) vs 25(12.3), P < 0.001]. This was also true for LES overall length [2.9(0.6) vs 2.6(0.6), P = 0.02] and intra-abdominal length [1.2(0.7) vs 0.8(0.8), P < 0.001]. Outflow resistance at the EGJ increased after MSA as demonstrated by elevation in intrabolus pressure (19.6 vs 13.5 mmHg, P < 0.001) and integrated relaxation pressure (13.5 vs 7.2, P < 0.001). MSA was also associated with an increase in distal esophageal body contraction amplitude [103.8(45.4) vs 94.1(39.1), P = 0.015] and distal contractile integral [2647.1(2064.4) vs 2099.7(1656.1), P < 0.001]. The percent peristalsis and incomplete bolus clearance remained unchanged ( P = 0.47 and 0.08, respectively). CONCLUSIONS: MSA results in improvement in the LES manometric characteristics. Although the device results in an increased outflow resistance at the EGJ, the compensatory increase in the force of esophageal contraction will result in unaltered esophageal peristaltic progression and bolus clearance.

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BACKGROUND: The performance and durability of various types of fundoplication are variable when stratified by disease severity. To date, magnetic sphincter augmentation (MSA) has not been evaluated in this context. We designed this study to determine the efficacy of MSA in the treatment of severe GERD. STUDY DESIGN: Guided by previous studies, a DeMeester score (DMS) ≥ 50 was used as a cutoff point to define severe reflux disease. Subjects were divided into 2 groups using this cutoff, and outcomes of severe cases were compared with those with less severe disease (DMS < 50). RESULTS: A total of 334 patients underwent MSA. Patients with severe disease had a higher mean preoperative DMS compared with those with mild to moderate GERD (79.2 [53.2] vs 22.8 [13.7], p < 0.0001). At a mean postoperative follow-up of 13.6 (10.4) months, there was no difference between the mean GERD Health-Related Quality of Life (HRQL) total scores in patients with severe disease compared with those with less severe GERD (8.8 [10] vs 9.2 [10.8], p = 0.9204). Postoperative mean DMS was not different between groups (17.3[23.0] vs 14.1[33.9], p = 0.71), and there was no difference in the prevalence of esophagitis (p = 0.52). Patients with severe disease were less likely to be free from use of proton pump inhibitors after surgery (85% vs 93.1%, p = 0.041). There were similar rates of postoperative dysphagia (10% vs 14%, p = 0.42) and need for device removal (3% vs 5%, p = 0.7463). CONCLUSIONS: MSA is an effective treatment in patients with severe GERD and leads to significant clinical improvement across the spectrum of disease severity, with few objective outcomes being superior in patients with mild-to-moderate reflux disease.

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BACKGROUND: Magnetic sphincter augmentation (MSA) is a promising surgical treatment for patients with GERD. The aim of this study was to evaluate the outcomes of MSA in a large cohort of patients with GERD and to determine the factors predicting a favorable outcome. METHODS: This was a retrospective review of prospectively collected data of 553 patients who underwent MSA at our institution in a 5-year period. Preoperative clinical, endoscopic, manometric, and pH data were used in a univariate analysis. This was followed by a regression multivariable analysis to determine the factors predicting a favorable outcome. Favorable outcome was defined as freedom from proton pump inhibitors and ≥50% improvement in Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) total score. RESULTS: At a mean (SD) follow-up of 10.3 (10.6) months after MSA, 92.7% of the patients were free of proton pump inhibitor use and 84% reported at least 50% improvement in their GERD-HRQL total score. The GERD-HRQL total score was improved from a mean (SD) baseline value of 33.8 (18.7) to 7.2 (9.0) (p < 0.001) and 76.1% of the patients had normalization of their esophageal acid exposure. Independent predictors of a favorable outcome after MSA included age younger than 45 years (odds ratio [OR] 4.2; 95% CI, 1.1 to 15.2; p = 0.0305), male sex (OR 2.5; 95% CI, 1.1 to 5.7; p = 0.0301), GERD-HRQL total score >15 (OR 7.5; 95% CI, 3.3 to 16.8; p < 0.0001), and abnormal DeMeester score (OR, 2.6; 95% CI, 1.1 to 5.7; p = 0.0225). CONCLUSIONS: In this largest single-institution series, we demonstrate that MSA implantation is associated with very good clinical and objective outcomes. Age younger than 45 years, male sex, GERD-HRQL total score >15, and abnormal DeMeester score are the 4 preoperative factors predicting a favorable outcome and can be used in patient counseling and MSA use.

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OBJECTIVE: To assess the efficacy of heat-shock protein 90 (Hsp90) inhibitor, NVP-AUY922-AG (AUY922), in the treatment of esophageal adenocarcinoma (EAC) in vitro and in vivo. BACKGROUND: EAC is a leading cause of cancer death, and current treatment options are limited. Hsp90, a chaperone protein that regulates several oncoproteins, is upregulated in EAC, and may be a novel target for therapy. METHODS: In vitro, EAC cell lines were utilized to evaluate AUY922, alone and in combination with 5-fluorouracil (5-FU) and cisplatin. BrdU ELISA and flow cytometry were used to assess proliferation and measure apoptosis, respectively. Western blot and RT-PCR were performed to quantitate Hsp90 pathway expression. In vivo, esophagojejunostomy was performed on rats and treatment animals received AUY922 32 to 40 weeks postoperatively. Drug efficacy was evaluated with magnetic resonance imaging (MRI), endoscopic biopsy, gross histological evaluation, and Hsp90 pathway expression. RESULTS: In vitro, AUY922 demonstrated antiproliferative activity in both cell lines and showed enhanced efficacy with cisplatin and 5-FU. Western Blot and RT-PCR demonstrated downregulation of CDK1 and CDK4 and upregulation of Hsp72. In vivo, AUY922 showed decrease in tumor volume in 36.4% of rats (control = 9.4%), increase in 9.1% (control = 37.5%), and stable disease in 54.5% (control = 43.7%). Necropsy confirmed the presence of EAC in 50% of treatment animals and 75% of control animals. mRNA expression, pre- and posttreatment, demonstrated significant downregulation of MIF, Hsp70, Hsp90ß, and CDK4, and upregulation of Hsp72. CONCLUSIONS: AUY922 exhibits antitumor efficacy in vitro and in vivo for EAC, suggesting the need for human clinical trials.

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BACKGROUND: The objective of this study is to evaluate the closure of a transgastric natural orifice transluminal endoscopic surgery (NOTES) access using a multilayer extracellular matrix (ECM) occluder in a canine model. MATERIALS AND METHODS: Mongrel dogs (n = 4) underwent a transgastric NOTES peritoneoscopy and the gastrotomy was closed by deploying a 2-sided ECM occluder. Animals were killed at 7 days (n = 2) and 8 weeks (n = 2) for macroscopic and microscopic assessment. RESULTS: All procedures were completed without any complications. No air leaks were detected immediately after the procedure and at 48 hours postoperatively. At 7 days, ECM appeared to be resolved and mild mucosal inflammation was found at the site of gastrotomy. At 8 weeks, the gastrotomy site was macroscopically and microscopically covered with a normal-appearing gastric mucosa. There was an absence of inflammatory cells and no evidence of the ECM. CONCLUSION: The ECM occluder is safe and effective in this "proof-of-concept" preclinical model.

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Previous studies have shown that the LPS of Helicobacter pylori isolated from North American and European hosts predominantly expresses type 2 Lewis x (Le(x)) and Le(y) epitopes, whilst the LPS from Asian strains has the capacity to express type 1 Le(a) and Le(b) structures. The aim of this study was to evaluate the expression of Le antigens and the cytotoxin-associated antigen (CagA) by H. pylori isolates from Chile. A total of 38 isolates were screened. The expression of Le antigens and CagA was determined by whole-cell indirect ELISA, using commercially available monoclonal anti-Le and polyclonal anti-CagA antibodies. LPS profiles of H. pylori isolates were assessed by gel electrophoresis and Western blotting. Expression of Le(x) and/or Le(y) epitopes was confirmed in 32/38 isolates (84 %), whilst 9/38 isolates (24 %) expressed type 1 Le(b) blood group determinants, in addition to type 2 Le(x) and Le(y) structures. Six strains (16 %) were non-typeable. The majority of H. pylori strains examined were CagA-positive (83.3 %).

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Information on the association between exposure to beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB) or polychlorinated biphenyls (PCBs) and the incidence of breast cancer is inconclusive. However, exposure to such compounds is a public health concern in Mexico and is subject to recent regulation. Serum levels of beta-HCH, HCB and PCBs were analysed in 95 histologically confirmed breast cancer cases and 95 hospital controls, 20-79 years of age, from Mexico City, enrolled between March 1994 and April 1996. After adjusting for established risk factors, there was no evidence of a relationship between beta-HCH, HCB and PCBs and breast cancer risk (OR for beta-HCH tertile 3 versus tertile 1: 1.05 95% CI 0.46-2.40; OR for HCB tertile 3 versus tertile 1: 0.46 95% CI 0.20-1.07; OR for PCBs 1.31 95% CI 0.33-5.21 for the high category of exposure). This study lends no support to the case for a role for beta-HCH, HCB or PCBs in breast cancer aetiology.

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Some, but not all, epidemiological studies have suggested that dichlorodiphenyltrichloroethane (DDT) may play a role in the development of breast cancer. These investigations have been conducted in countries where this substance has been banned for at least 20 years. We conducted a study in Mexico, a country in which DDT is still being used to control malaria. In a hospital-based case-control study, we compared 141 histologically confirmed cases of breast cancer with 141 age-matched controls (+/-3 years). All subjects were identified at three referral hospitals of Mexico City between March 1994 and April 1996. Reproductive histories and other variables were obtained by structured interviews, DDT/DDE levels were determined in serum by gas-liquid chromatography. The arithmetic mean of serum DDE in lipid basis was 562.48 +/- 676.18 ppb (range, 10.24-4661.44) for the cases and 505.46 +/- 567.22 ppb (range, 0.004 to 4361.75) for the controls, but this difference was not statistically significant. The age-adjusted odds ratios for breast cancer regarding the serum level of DDE were 0.69 (95% confidence interval, 0.38-1.24) and 0.97 (confidence interval, 0.55-1.70) for the contrasts between tertile 1 (lowest level) and tertiles 2 and 3, respectively. These estimates were unaffected by adjustment for body mass, accumulated time of breast-feeding and menopause, and other breast cancer risk factors. These results do not lend support to the hypothesis that DDT is causally related to breast cancer at the body-burden levels found in our study population but do not exclude the possibility that higher levels of exposure could still play a role in the etiology of this tumor.

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It might be expected that infections with transmissible agents will elicit an immune response to all of their exoantigens and that immune response (Ir) gene control of responses to individual epitopes on a given parasite component would be obscured by reaction to the molecule as a whole. Humans infected with parasitic nematodes, however, mount antibody responses which are selective for certain parasite components. This was modelled in inbred rats infected with the parasitic nematode Nippostrongylus brasiliensis and their responses to secreted antigens analysed by immunoprecipitation and SDS-PAGE. No strain responded to all the potential antigens and only those of identical major histocompatibility complex (MHC) had similar recognition profiles. This MHC-restricted response applied to whole molecules synthesized by the parasite, rather than merely to epitopes thereon and is, therefore, contrary to expectation. Moreover, the response patterns of F1 hybrid animals were not merely summations of parental responses. This suggests defective antigen presentation of particular parasite components by certain MHC class II molecules and/or cross-tolerance with background gene products.

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Negative electrical current appears to have a bacteriostatic effect on the in vivo growth of Pseudomonas aeruginosa when applied to surface wounds on rabbits; this experimental procedure causes the bacterial count over a 72-hr period of application to remain stable or decreased in most cases. Infected wounds without electrical treatment displayed an increase in bacterial count. Enhancement of antibiotic activity was also detected in the present of the copper mesh electrode with and without current. The infected wound treated with an electrode and no current or antibiotic demonstrated no effects on bacterial growth. These in vivo results correlate with in vitro data previously reported and substantiate observed effects of electrical currents on ischemic skin ulcers. The apparent enhancement of antibiotic activity in the presence of the copper mesh electrode was unexpected, particulary bacause the copper electrode alone had no effect on the infected wound

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