Roux-en-Y gastric bypass affects the expression of genes related to the intestinal folate metabolism pathway in obese women.

OBJECTIVES: Roux-en-Y gastric bypass (RYGB) promotes sustained weight loss, and the resulting new gastrointestinal anatomy can contribute to nutritional depletions. Folate deficiency is one of the most frequently observed nutritional deficiencies after RYGB. The aim of this study was to assess whether RYGB affects the expression of genes related to the intestinal folate metabolism pathway as an additional molecular mechanism contributing to its postoperative deficiency. METHODS: Biopsies from the duodenum, jejunum, and ileum of 20 obese women were collected before and 3 mo after RYGB. The expression of genes involved in intestinal folate metabolism was assessed by microarray and reverse transcriptase polymerase chain reaction (RT-qPCR). Folate intake (7-d food record) and plasma levels (electrochemiluminescence) also were measured. RESULTS: Compared with the preoperative phase, transcriptomic alterations were observed in all intestinal segments studied after RYBG, mainly marked by decreased expression of genes encoding folate transporters/receptors and increased expression of genes involved in folate biosynthesis (P < 0.05). Reduced folate intake and plasma folate levels were also observed simultaneously (P < 0.05). Plasma folate concentrations correlated inversely with intestinal FOLR2 and SHMT2 genes (P < 0.001). CONCLUSION: The present findings suggested that impaired expression of genes related to intestinal folate metabolism may contribute to the early systemic deficiency after RYGB and highlight a potential transcriptomic reprogramming of the intestine in response to RYGB to compensate for folate depletion induced by this surgical technique.

Gastrointestinal genetic reprogramming of vitamin A metabolic pathways in response of Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is one of the most performed bariatric surgical techniques. However, RYGB commonly results, as side effects, in nutritional deficiencies. This study aimed to examine changes in the expression of vitamin A pathway encoding genes in the gastrointestinal tract (GI) and to evaluate the potential mechanisms associated with hypovitaminosis A after RYGB. Intestinal biopsies were obtained through double-balloon endoscopy in 20 women with obesity (age 46.9±6.2 years; body mass index [BMI] 46.5±5.3 kg/m2 [mean±SD]) before and three months after RYGB (BMI, 38.2±4.2 kg/m2). Intestinal mucosal gene microarray analyses were performed in samples using a Human GeneChip 1.0 ST array (Affymetrix). Vitamin A intake was assessed from 7-day food records and serum retinol levels were evaluated by electrochemiluminescence immunoassay. Our results showed the following genes with significant downregulation (p≤0.05): LIPF (-0.60), NPC1L1 (-0.71), BCO1 (-0.45), and RBP4 (-0.13) in duodenum; CD36 (-0.33), and ISX (-0.43) in jejunum and BCO1 (-0.29) in ileum. No significant changes in vitamin A intake were found (784±694 retinol equivalents [RE] pre-operative vs. 809±753 RE post-operative [mean±SD]). Although patients were routinely supplemented with 3500 international units IU/day (equivalent to 1050 µg RE/day) of oral retinol palmitate, serum concentrations were lower in the post-operative when compared to pre-operative period (0.35±0.14 µg/L vs. 0.52±0.33 µg/L, respectively - P=0.07), both within the normal range. After RYGB, the simultaneous change in expression of GI genes, may impair carotenoid metabolism in the enterocytes, formation of nascent chylomicrons and transport of retinol, resulting in lower availability of vitamin A.

Genetic reprogramming of remnant duodenum may contribute to type 2 diabetes improvement after Roux-en-Y gastric bypass.

OBJECTIVES: Type 2 diabetes control occurs within a few days after Roux-en-Y gastric bypass (RYGB) and might be related to intestinal adaptation to the new anatomic arrangement. The aim of this study was to evaluate the intestinal transcriptome response to RYGB and its correlation with markers of glycemic homeostasis. METHODS: Global transcriptomic analyses performed by microarray technique were conducted in intestinal biopsies collected from adult women with obesity (N = 20) and T2D before and 3 mo after RYGB. Clinical and biochemical markers of glycemic homeostasis were also evaluated. At 1-y postoperative, patients were classified as responsive (R) or non-responsive (NR) to complete T2D remission according to the American Diabetes Association criteria. Intestinal differentially expressed genes (DEGs) were analyzed separately in the two groups, validated by reverse transcription quantitative polymerase chain reaction, and applied in functional enrichment and canonical pathway analysis. Spearman correlations between clinical and biochemical variables with DEGs were conducted. Twelve patients were classified as R and displayed 62 (duodenum), 241 (jejunum), and 63 (ileum) DEGs. RESULTS: Eight of the patients with DEGs presented very strong or strong positive correlations with glycemia or glycated hemoglobin. Duodenal changes of genes involved in the LXR/RXR pathway were more likely to be associated with T2D. CONCLUSION: In obese women, complete remission of T2D after RYGB might include intestinal transcriptomic changes that suggest a potential role of intracellular cholesterol and lipid homeostasis on glucose control.

Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission.

OBJECTIVES: Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr METHODS: Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. RESULTS: Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. CONCLUSIONS: RYGB-induced weight loss-independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery.

Type 2 Diabetes Metabolic Improvement After Roux-en-Y Gastric Bypass May Include a Compensatory Mechanism That Balances Fatty Acid ß and ω Oxidation.

BACKGROUND: More than half of patients who undergo Roux-en-Y gastric bypass (RYGB) can experience type 2 diabetes (T2D) remission, but the systemic and gastrointestinal (GI) metabolic mechanisms of this improvement are still elusive. METHODS: Paired samples collected before and 3 months after RYGB from 28 women with obesity and T2D were analyzed by metabolomics with gas chromatography coupled to mass spectrometry. Samples include plasma (n = 56) and biopsies of gastric pouch (n = 18), gastric remnant (n = 10), duodenum (n = 16), jejunum (n = 18), and ileum (n = 18), collected by double-balloon enteroscopy. RESULTS: After RYGB, improvements in body composition and weight-related and glucose homeostasis parameters were observed. Plasma-enriched metabolic pathways included arginine and proline metabolism, urea and tricarboxylic acid (TCA) cycles, gluconeogenesis, malate-aspartate shuttle, and carnitine synthesis. In GI tissue, we observed alterations of ammonia recycling and carnitine synthesis in gastric pouch, phenylacetate metabolism and trehalose degradation in duodenum and jejunum, ketone bodies in jejunum, and lactose degradation in ileum. Intermediates molecules of the TCA cycle were enriched, particularly in plasma, jejunum, and ileum. Fluctuations of dicarboxylic acids (DCAs) were relevant in several metabolomic tests, and metabolite alterations included aminomalonate and fumaric, malic, oxalic, and succinic acids. The product/substrate relationship between these molecules and its pathways may reflect a compensatory mechanism to balance metabolism. CONCLUSIONS: RYGB was associated with systemic and GI metabolic reprogramming. DCA alterations link ω and ß fatty acid oxidation to homeostatic mechanisms, including TCA cycle improvement.

Potential premalignant status of gastric portion excluded after Roux en-Y gastric bypass in obese women: A pilot study.

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient's life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass.

BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) limits food ingestion and may alter the intestinal expression of genes involved in the endogenous synthesis of polyunsaturated fatty acids (PUFAs). These changes may decrease the systemic availability of bioactive PUFAs after RYGB. To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFAs and on the intestinal expression of genes involved in their endogenous biosynthesis in severely obese women with type 2 diabetes. METHODS: Before, and 3 and 12 months after RYGB, obese women (n = 20) self-reported a seven-day dietary record, answered a food frequency query and provided plasma samples for alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acid assessment by gas chromatography. Intestinal biopsies (duodenum, jejunum and ileum) were collected through double-balloon endoscopy before and 3 months after RYGB for gene expression analysis by microarray (Human GeneChip 1.0 ST array) and RT-qPCR validation. RESULTS: Compared to the preoperative period, patients had decreased intakes of PUFAs, fish and soybean oil (p < 0.05) and lower plasma concentrations of ALA and EPA (p < 0.001) 3 and 12 months after RYGB. FADS1 gene expression was lower in duodenum (RT-qPCR fold change = -1.620, p < 0.05) and jejunum (RT-qPCR fold change = -1.549, p < 0.05) 3 months following RYGB, compared to before surgery. CONCLUSION: RYGB decreased PUFA ingestion, plasma ALA and EPA levels, and intestinal expression of FADS1 gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFAs. These data suggest that supplementation of omega-3 PUFAs may be required for obese patients undergoing RYGB. Clinical Trial Registry number and website: www.clinicaltrials.gov - NCT01251016; Plataforma Brasil - 19339913.0.0000.0068.

Carbon dioxide versus air insufflation enteroscopy: a systematic review and meta-analysis based on randomized controlled trials.

OBJECTIVES: To compare the insufflation of CO 2 and ambient air in enteroscopy. SEARCH SOURCES: The investigators researched the electronic databases MedLine, Cochrane Library, Central, LILACS, BVS, Scopus and Cinahl. The grey search was conducted in the base of theses of the University of São Paulo, books of digestive endoscopy and references of selected articles and in previous systematic revisions. STUDY ELIGIBILITY CRITERIA: The evaluation of eligibility was performed independently, in a non-blind manner, by two reviewers, firstly by title and abstract, followed by complete text. Disagreements between the reviewers were resolved by consensus. DATA COLLECTION AND ANALYSIS METHOD: Through the spreadsheet of data extraction, where one author extracted the data and a second author checked the extraction. Disagreements were resolved by debate between the two reviewers. The quality analysis of the studies was performed using the Jadad score. The software RevMan 5 version 5.3 was used for the meta-analysis. RESULTS: Four randomized clinical trials were identified, totaling 473 patients submitted to enteroscopy and comparing insufflation of CO 2 and ambient air. There was no statistical difference in the intubation depth between the two groups. When CO 2 insufflation was reduced, there was a significant difference in pain levels 1 hour after the procedure (95 % IC, -2.49 [-4.72, -0.26], P : 0.03, I 2 : 20%) and 3 hours after the procedure (95% IC, -3.05 [-5.92, -0.18], P : 0.04, I 2 : 0 %). There was a usage of lower propofol dosage in the CO 2 insufflation group, with significant difference (95 % IC, -67.68 [-115.53, -19.84], P : 0.006, I 2 : 0 %). There was no significant difference between the groups in relation to the use of pethidine and to the oxygen saturation. LIMITATIONS: Restricted number of randomized clinical trials and nonuniformity of data were limitations to the analysis of the outcomes. CONCLUSION: The use of CO 2 as insufflation gas in enteroscopy reduces the pain levels 1 hour and 3 hours after the procedure, in addition to the reduction of the sedation (propofol) dosage used.

Computed tomography colonography versus colonoscopy for the diagnosis of colorectal cancer: a systematic review and meta-analysis.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality. Optical colonoscopy (OC) is the first choice of investigation for assessing the state of the colon and it is excellent for CRC screening. Newer technologies such as computed tomography colonography (CTC) may also be useful in CRC screening. This systematic review compares the benefits of CTC and OC for CRC screening. This review includes all the available randomized clinical trials comparing CTC and OC for CRC screening in asymptomatic patients. Three studies were included in the systematic review and were submitted for meta-analysis. In the analysis of participation rates, only 2,333 of 8,104 (29%) patients who were invited for screening underwent the CTC, and only 1,486 of the 7,310 (20%) patients who were invited for screening underwent OC. The absolute risk difference in participation rate in the two procedures was 0.1 (95% CI, 0.05-0.14) in favor of CTC. In the analysis of advanced colorectal neoplasia (ACN) detection rates, 2,357 patients undergoing CTC and 1,524 patients undergoing OC were included. Of these, 135 patients (5.7%) who underwent a CTC and 130 patients (8.5%) who underwent an OC were diagnosed with ACN. The absolute risk difference in ACN detection rate in the two procedure types was -0.02 (with a 95% CI between -0.04 and -0.00) in favor of OC. CTC is an option for CRC screening in asymptomatic patients. However, as CTC was inferior in detecting ACN, it should not replace OC, which remains the gold standard.

Video capsule endoscopy vs double-balloon enteroscopy in the diagnosis of small bowel bleeding: A systematic review and meta-analysis.

AIM: To compare the diagnostic accuracy of video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) in cases of obscure gastrointestinal bleeding (OGIB) of vascular origin. METHODS: MEDLINE (via PubMed), LILACS (via BVS) and Cochrane/CENTRAL virtual databases were searched for studies dated before 2017. We identified prospective and retrospective studies, including observational, cohort, single-blinded and multicenter studies, comparing VCE and DBE for the diagnosis of OGIB, and data of all the vascular sources of bleeding were collected. All patients were subjected to the same gold standard method. Relevant data were then extracted from each included study using a standardized extraction form. We calculated study variables (sensitivity, specificity, prevalence, positive and negative predictive values and accuracy) and performed a meta-analysis using Meta-Disc software. RESULTS: In the per-patient analysis, 17 studies (1477 lesions) were included. We identified 3150 exams (1722 VCE and 1428 DBE) in 2043 patients and identified 2248 sources of bleeding, 1467 of which were from vascular lesions. Of these lesions, 864 (58.5%) were diagnosed by VCE, and 613 (41.5%) were diagnosed by DBE. The pretest probability for bleeding of vascular origin was 54.34%. The sensitivity of DBE was 84% (95%CI: 0.82-0.86; heterogeneity: 78.00%), and the specificity was 92% (95%CI: 0.89-0.94; heterogeneity: 92.0%). For DBE, the positive likelihood ratio was 11.29 (95%CI: 4.83-26.40; heterogeneity: 91.6%), and the negative likelihood ratio was 0.20 (95%CI: 0.15-0.27; heterogeneity: 67.3%). Performing DBE after CE increased the diagnostic yield of vascular lesion by 7%, from 83% to 90%. CONCLUSION: The diagnostic accuracy of detecting small bowel bleeding from a vascular source is increased with the use of an isolated video capsule endoscope compared with isolated DBE. However, concomitant use increases the detection rate of the bleeding source.

Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass.

OBJECTIVES: Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency. METHODS: During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR). RESULTS: Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold). CONCLUSIONS: RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.

The SURMetaGIT study: Design and rationale for a prospective pan-omics examination of the gastrointestinal response to Roux-en-Y gastric bypass surgery.

Objective To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study's design and challenges faced in its application are detailed. Methods This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission. Results Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation. Conclusion The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.

Asymptomatic gastric bacterial overgrowth after bariatric surgery: are long-term metabolic consequences possible?

BACKGROUND: Patients with postbariatric bacterial overgrowth were reinvestigated after a follow-up of 15 years. It was hypothesized that systemic associations analogous to those reported for whole gut microbiome would be revealed. METHODS: Patients (n = 37, 70.3 % females, 42.4 ± 9.9 years old, preoperative BMI 53.5 ± 10.6 kg/m(2), current BMI 32.8 ± 10.8 kg/m(2)), all submitted to RYGB on account of morbid obesity, were followed during 176.8 ± 25.7 months. Blood tests included fasting blood glucose, HbA1c, liver and pancreatic enzymes, and lipid fractions. Bacterial overgrowth was diagnosed by quantitative culture of gastric fluid in both the excluded remnant and the gastric pouch, with the help of double-balloon enteroscopy. Absolute counts of aerobes and anaerobes in both gastric reservoirs were correlated with nutritional and biochemical measurements, aiming to identify clinically meaningful associations. RESULTS: Patients denied diarrhea, abdominal pain, weight loss, or other symptoms related to bacterial overgrowth. Biochemical profile including enzymes was also acceptable, indicating a stable condition. Positive correlation of bacterial count in either segment of the stomach was demonstrated for BMI and gamma-glutamyl transferase, whereas negative correlation occurred regarding fasting blood glucose. CONCLUSIONS: An antidiabetic role along with deleterious consequences for weight loss and liver function are possible in such circumstances. Such phenotype is broadly consistent with reported effects for the whole gut microbiome. Prospective controlled studies including molecular analysis of gastrointestinal fluid, and simultaneous profiling of the entire microbiome, are necessary to shed more light on these findings.

Epithelial cell turnover is increased in the excluded stomach mucosa after Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Mucosal alterations after Roux-en-Y gastric bypass for morbid obesity have not been clearly evaluated. This study aims to analyze the mucosal alterations (proliferative status (Ki-67); apoptosis (caspase-3 and BCL-2); hormonal function (gastrin)) in the excluded stomach. METHODS: Double-balloon enteroscopy was performed in 35 patients who underwent Roux-en-Y gastric bypass longer than 36 months. Multiple biopsies of the proximal pouch and the excluded gastric mucosa were collected. Gastric biopsies from 32 non-operated obese patients were utilized as controls. Endoscopic biopsies were cut from tissue blocks fixed in formalin and embedded in paraffin. Sections 4 µm thick were examined for immunoexpression using the streptavidin-biotin-peroxidase method. RESULTS: The two groups were comparable for age, gender, gastritis, intestinal metaplasia, and Helicobacter pylori. The mean number of positive gastrin cells was 55.5 (standard deviation (SD) = 11.7) in the control group and 29.6 (SD = 7.9) in the cases, p = 0.0003. Ki-67 proliferative index in cases (body = 24.7%, antrum = 24.9%) was significantly higher compared to controls (body = 15.0% and antrum = 17.7%), p = 0.002 and 0.01, respectively. Caspase-3 immunoexpression was higher in the controls compared to the excluded stomach (46 vs. 31%), p = 0.02. There was no statistical difference between CD3, CD8, and Bcl-2 immunoexpressions in the control and cases. CONCLUSIONS: Cell proliferation is increased and apoptosis is downregulated in the excluded gastric mucosa compared to the non-operated obese controls. Alterations in cell turnover and in hormonal secretions in these conditions may be of relevance in long-term follow-up.

Small bowel endoscopy using the double-balloon technique: four-year results in a tertiary referral hospital in Brazil.

BACKGROUND: Double-balloon enteroscopy (DBE) allows evaluation and therapy for various small bowel diseases. In this series the outcome of a 4-year experience in a tertiary hospital school in Brazil is reported. METHODS: A total of 457 consecutive DBE were performed in 418 patients from August 2004 to August 2008. 93 patients with several indications, whose aim was not the evaluation of suspected diseases of the small bowel mucosa, were excluded, therefore leaving 364 DBE in 325 patients for analysis. Data were retrospectively collected with regard to clinical, endoscopic findings, therapy and complications. RESULTS: Among the 364 DBE performed in 325 patients, 143/325 were males (44%) and 182/325 females (56%) with a mean age of 48.6 +/- 15.7 years (range 17-89). Mean investigation time was 64 +/- 22 min (range 35-135). The depth of insertion beyond the ligament of Treitz was 230 +/- 85 cm (range 30-500) by the antegrade approach and 140 +/- 75 cm (range 0-320) by the retrograde approach. Total enteroscopy was achieved in 41.66% of the attempts (30 of 72 patients). Overall diagnostic yield was 54.95% (200 of 364 procedures) ranging from 0 to 100% in this series, depending on the indication. Angiodysplasia was the main diagnosis in 24.5% (49 of 200 procedures) and endoscopic treatment, including biopsies, hemostasis, tattooing and polypectomy were performed in 65.38% (238 of 364 procedures). No major complications were reported. CONCLUSIONS: DBE is a feasible, safe and well-tolerated procedure allowing endoscopic therapy. Selection of indications increases its diagnostic yield.

Endoscopic findings in the excluded stomach after Roux-en-Y gastric bypass surgery.

HYPOTHESIS: After gastric bypass surgery performed because of morbid obesity, the excluded stomach can rarely be endoscopically examined. With the advent of a new apparatus and technique, possible mucosal changes can be routinely accessed and monitored, thus preventing potential benign and malignant complications. DESIGN: Prospective observational study in a homogeneous population with nonspecific symptoms. SETTING: Outpatient clinic of a large public academic hospital. PATIENTS: Forty consecutive patients (mean +/- SD age, 44.5 +/- 10.0 y ears; 85.0% women) were seen at a mean +/- SD of 77.3 +/- 19.4 months after Roux-en-Y gastric bypass surgery. INTERVENTION: Elective double-balloon enteroscopy of the excluded stomach was performed. MAIN OUTCOME MEASURES: Rate of successful intubation, endoscopic findings, and complications. RESULTS: The excluded stomach was reached in 35 of 40 patients (87.5%). Mean +/- SD time to enter the organ was 24.9 +/- 14.3 minutes (range, 5-75 minutes). Endoscopic findings were normal in 9 patients (25.7%), whereas in 26 (74.3%), various types of gastritis (erythematous, erosive, hemorrhagic erosive, and atrophic) were identified, primarily in the gastric body and antrum. No cancer was documented in the present series. Tolerance was good, and no complications were recorded during or after the intervention. CONCLUSIONS: The double-balloon method is useful and practical for access to the excluded stomach. Although cancer was not noted, most of the studied population had gastritis, including moderate and severe forms. Surveillance of the excluded stomach is recommended after Roux-en-Y gastric bypass surgery performed because of morbid obesity.

Increased gastric cytokine production after Roux-en-Y gastric bypass for morbid obesity.

HYPOTHESIS: Mucosal cytokines may be involved in the process of gastric bacterial contamination that may occur after Roux-en-Y bypass for morbid obesity in both gastric chambers, with inflammation and gastritis mostly in the excluded stomach. DESIGN: A prospective observational study in a homogeneous population with nonspecific complaints. SETTING: Outpatient clinic of a large, public, academic hospital. PATIENTS: Subjects (n = 37; 26 [70.3%] female; mean +/- SD age, 42.4 +/- 9.9 years) seen a mean +/- SD of 7.3 +/- 1.4 years after Roux-en-Y gastric bypass and nonoperated on morbidly obese control subjects (n = 10; 7 [70%] female; mean +/- SD age, 44.0 +/- 8.9 years). INTERVENTION: Enteroscopy was performed to collect samples for cytokine assays and bacteriologic studies. MAIN OUTCOME MEASURES: Concentrations of tumor necrosis factor alpha and transforming growth factor beta in the gastric mucosa of both chambers in patients undergoing Roux-en-Y gastric bypass and correlation with bacterial overgrowth and Helicobacter pylori infection. RESULTS: High microbial counts (>10(5) colony-forming units per milliliter) were detected in 22 (59.5%) and 7 (18.9%) of the 37 samples from the functional pouch and excluded reservoir, respectively; and H pylori investigation was positive in 6 of 37 samples (16.2%). The tumor necrosis factor alpha concentration (mean +/- SD, 2.1 +/- 1.9 pg/g of protein) and the transforming growth factor beta concentration (mean +/- SD, 24.2 +/- 12.8 pg/g of protein) in the excluded stomach, but not in the proximal pouch, were elevated with regard to the corpus or antrum of controls, and correlation with bacterial overgrowth and with H pylori infection was demonstrated. CONCLUSION: Overexpression of tumor necrosis factor alpha and transforming growth factor beta occurred in the distal stomach, positive cytokine correlation with microbial invasion by H pylori and nonspecific germs was seen, and further studies addressing phenotypic and genotypic changes of gastric mucosa are recommended.

Microbial flora of the stomach after gastric bypass for morbid obesity.

BACKGROUND: The normal stomach is virtually sterile but the effect of Roux-en-Y gastric bypass (RYGBP) on bacterial flora in the used (very small proximal pouch) and unused (large bypassed) gastric chambers is not known. In a prospective study, this variable was documented. METHODS: Bariatric subjects (n=37) were submitted to endoscopic examination of both gastric reservoirs via FUJINON enteroscope model EN-450P5, 7.3 +/- 1.4 years after RYGBP. Age was 42.4 +/- 9.9 years (70.2% females), preoperative BMI was 53.5 +/- 10.6, and current BMI was 32.6 +/- 7.8 kg/m2. Methods included quantitative culture of gastric secretion along with gastric pH and lactulose/hydrogen breath test. RESULTS: None of the subjects displayed diarrhea, malabsorption or other complaints suggestive of GI bacterial overgrowth. Elevated counts of bacteria and fungi were identified in both chambers, with predominance of aerobes and anaerobes, but not molds and yeasts, in the proximal stomach. Gram-positive cocci, bacilli and coccobacilli represented the majority of the isolates. Gastric pH was neutral (pH 7.0 +/- 0.2) in the proximal pouch, whereas the distal chamber mostly but not always conserved the expected acidity (pH 3.3 +/- 2.2, P<0.001). The breath test for bacterial overgrowth was positive in 40.5% of the population. CONCLUSIONS: 1) Frequent colonization of both gastric chambers was detected; 2) Aerobes, anaerobes and fungi were represented in both situations; 3) Gastric pH as well as bacterial count was higher in the functioning proximal stomach; 4) Breath test was positive in 40.5% of the subjects; 5) Clinical manifestation such as diarrhea, malabsorption or pneumonia were not demonstrated; 6) Further histologic and microbiologic studies of both the stomach and the small bowel are recommended.

Endoscopic and ultrasonographic evaluation before and after Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Esophagogastric abnormalities are recognized prior and after bariatric procedures, but frequency and severity are debated. Liver and biliary tract findings are also of clinical importance, especially gallstones and liver steatosis. AIM: To compare pre-operative findings of hepatobiliary ultrasound and upper digestive endoscopy with post-operative results in patients submitted to open Roux-en-Y gastric bypass for morbid obesity. METHODS: A total of 80 patients were enrolled 16.8 +/- 12.1 months after operation, all of them on routine follow-up program, and 8 were excluded. Retrospective analysis aimed at pre-operative clinical, endoscopic and ultrasonographic examinations and were prospectively repeated. RESULTS: Pre-operative endoscopical report was available in 42 cases, and 52 examinations were performed post-operatively. Frequency of esophagitis changed from 16.7% (7/42) to 15.4% (8/52), and of gastritis from 45.2% (19/42) to 21.2% (11/52). Gastric or gastrojejunal ulcers were initially present in 4.8% (2/42) and increased to 9.6% (5/52). Post-operatively, an unusual abnormality was silastic band erosion: 7.7% (4/52). Helicobacter pylori was present in 50.0% (21/42) before and 3.5% (2/52) after operation. Ultrasonographic study had been done before intervention in 63 subjects, and 57 were executed on follow-up. Liver steatosis occurred previously in 58.7% (37/63) and in 43.9% (25/57) later on. Only 12.7% (8/63) of the patients had undergone cholecystectomy before bariatric operation, 29.1%(16/55) suffered simultaneous resection of gallbladder because of stones during Roux-en-Y gastric bypass, and an additional 26.8% (10/36) developed gallstones post-operatively. CONCLUSIONS: Liver steatosis did not statistically improve, nor did inflammatory conditions of the upper digestive tube, despite reduction of H. pylori infections; gallbladder stones requiring intervention were common.

Is double-balloon enteroscopy an accurate method to diagnose small-bowel disorders?

BACKGROUND AND STUDY AIMS: The aim of this study was to analyze the contribution of the double-balloon enteroscopy (DBE) for diagnosis of the small bowel disorders. PATIENTS AND METHODS: Forty-four patients (20 women, 24 men; mean age 53.5 years-old, range 21-89 years) with chronic gastrointestinal bleeding, diarrhea, polyposis, weight-loss, Roux-en-Y surgery, and other indications underwent DBE. RESULTS: Twenty patients had occult or obscure gastrointestinal bleeding. The source of bleeding was identified in 15/20 (75%): multiple angiodysplasias in four, arterial-venous malformation beyond the ligament of Treitz in two that could be treated with injection successfully. Other diagnoses included: duodenal adenocarcinoma, jejunal tuberculosis, erosions and ulcer of the jejunum. Of 24 patients with other indications, the diagnosis could be achieved in 18 of them (75%), including: two lymphomas, plasmocytoma, Gardner's syndrome, Peutz-Jeghers' syndrome, familial adenomatous polyposis, Behçet's disease, jejunal submucosal lesion, lymphangiectasia due to blastomycosis and unspecific chronic jejunitis. Of three cases with Roux-en-Y reconstruction, two underwent DBE in order to perform biopsies of the excluded duodenum. Additionally, two patients underwent DBE to exclude Crohn's disease and lymphoma of the small bowel. The mean length of small bowel examination was 240 +/- 50 cm during a single approach. The diagnostic yield was 75% (33/44 cases) and therapeutic yield was 63.6%. No major complications were observed, only minor complication such as sore throat in 4/44 (9.1%). CONCLUSIONS: 1. DBE is a safe and and accurate method to diagnose small bowel disorders; 2. this method permits chromoscopy, biopsies and treatment of the lesions.