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Background and Aims: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The suprapapillary method of stent placement may reduce DBR and improve stent patency compared with the transpapillary method. This study compared the clinical outcomes between the suprapapillary and transpapillary methods for distal malignant biliary obstruction (DMBO)., Methods: Between January 2021 and January 2023, consecutive patients with DMBO from 6 centers in South Korea were randomly assigned to either the suprapapillary arm or transpapillary method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes were the cause of stent dysfunction, adverse events, and overall survival rate., Results: Eighty-four patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (50, 59.5%), followed by bile duct (20, 23.8%), gallbladder (11, 13.1%), and other cancers (3, 3.6%). Stent patency was significantly longer in the suprapapillary group (median, 369 days [interquartile range, 289-497] vs 154 days [interquartile range, 78-361]; P < .01). Development of DBR was significantly lower in the suprapapillary group (9.4% vs 40.8%, P < .01). Adverse events and overall survival rate were not significantly different between the 2 groups., Conclusions: The placement of SEMSs using the suprapapillary method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the suprapapillary method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the suprapapillary method. (Clinical trial registration number: KCT0005572.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by TaeWoong Medical Co, Ltd., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Occult pancreaticobiliary reflux (OPBR) has a significant correlation with diseases of the gallbladder and biliary system. This study examined the incidence of OPBR by age in patients with benign gallbladder diseases., Methods: We assessed 475 patients with benign gallbladder diseases who underwent surgery at Shanghai East Hospital from December 2020 to December 2021. Bile samples collected during surgery were tested for amylase. Patients with bile amylase >110 U/L ( n  = 64) were classified as the OPBR group; the rest ( n  = 411) as controls., Results: Of the participants, 375 had gallbladder stone (GS), 170 had gallbladder polyp (GP), and 49 had gallbladder adenomyomatosis (GA). The OPBR group was generally older, with OPBR incidence increasing with age, peaking post-45. Rates by age were: 4.9% (<35), 5.2% (35-44), 20.7% (45-54), 22.5% (55-64) and 17.6% (≥65), mainly in GS patients. ROC analysis for predicting OPBR by age yielded an area under the curve of 0.656, optimal cut-off at 45 years. Logistic regression indicated age > 45, GP, male gender, and BMI ≥ 24 kg*m -2 as independent OPBR predictors in GS patients. Based on these variables, a predictive nomogram was constructed, and its effectiveness was validated using the ROC curve, calibration curve and decision curve analysis (DCA). Further stratification revealed that among GS patients ≤ 45, concurrent GA was an OPBR risk; for > 45, it was GP and male gender., Conclusions: The incidence of OPBR in GS patients is notably influenced by age, with those over 45, especially males without GP, being at heightened risk.

Background: Although bile reflux plays an important role in the development of Barrett's esophagus, the relationship between endoscopic findings of bile reflux and Barrett's esophagus remains unclear., Objective: This study evaluated whether endoscopic evidence of bile reflux was associated with the presence of Barrett's esophagus., Methods: A retrospective analysis of a prospectively maintained database comprising consecutive patients who underwent screening esophagogastroduodenoscopy was conducted. Endoscopic evidence of bile reflux was defined as the presence of bile-stained fluid in the gastric fundus. We performed multivariate analysis to identify predictive factors that differed significantly between patients with and without Barrett's esophagus., Results: Of 4021 patients, 922 (23%) had Barrett's esophagus, and 1000 (25%) showed endoscopic findings of bile reflux. Multivariate analysis revealed endoscopic evidence of bile reflux as the strongest independent factor associated with the presence of Barrett's esophagus (odds ratio [OR] 5.65, 95% confidence interval [CI] 4.71-6.76) in relation to the presence of hiatal hernia (OR 3.30, 95% CI 2.70-4.04) and male gender (OR 1.54, 95% CI 1.24-1.91)., Conclusions: Endoscopic evidence of bile reflux was independently associated with the presence of Barrett's esophagus. This finding might help identify patients at future risk of Barrett's esophagus who could benefit from increased endoscopy surveillance., Competing Interests: Conflict of interest None., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: One anastomosis gastric bypass (OAGB) is mainly criticized for the supposed carcinogenic effect of bile reflux on the gastric pouch mucosa., Case Presentation: A 56-year-old male patient presented 12 years after OAGB with a 10-month history of gradual dysphagia and vomiting. He was diagnosed with a tumor of the gastro-jejunal anastomosis, and underwent total gastrectomy with D2 lymphadenectomy. Specimen examination showed a diffuse isolated cell-type adenocarcinoma. To our knowledge, we report the first case in literature of adenocarcinoma of the gastro-jejunal anastomosis post-OAGB, and the second reported case if we include the Mason loop gastric bypass, which was the earlier version of OAGB with a different conceptual and physiological aspect., Conclusion: The carcinogenic effect of bile reflux in OAGB will remain hypothetical until a detailed controlled study may prove the causality between bile reflux and gastric pouch malignancies in patients with a history of OAGB., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study retrospectively analyzed the clinical efficacy of Uncut Roux-en-Y and Billroth II anastomoses in gastrointestinal reconstruction following laparoscopic D2 radical gastrectomy for distal gastric cancer. The primary objective was to compare the postoperative outcomes, including quality of life and complication rates, between the 2 surgical techniques. One hundred patients diagnosed with distal gastric cancer were enrolled between June 2020 and May 2023. Patients underwent laparoscopic D2 gastrectomy and were categorized into either the Uncut Roux-en-Y or Billroth II anastomosis groups based on the technique used for gastrointestinal reconstruction. The inclusion and exclusion criteria were strictly followed. Surgical parameters, quality of life assessed using the Visick grading index, and postoperative complications were also evaluated. Statistical analyses were performed using SPSS version 27.0. The groups were comparable in terms of demographic and baseline clinical parameters. The Uncut Roux-en-Y group had a significantly longer duration of surgery (P < .001). However, there were no statistically significant differences in other surgical parameters. According to the Visick grading index, patients in the Uncut Roux-en-Y group reported a significantly better quality of life than those in the Billroth II group (P < .05). Additionally, Uncut Roux-en-Y was associated with a significantly lower incidence of dumping syndrome and bile reflux (P < .05). Although Uncut Roux-en-Y anastomosis requires longer surgical time, it offers significant advantages in terms of postoperative quality of life and reduced rates of dumping syndrome and bile reflux. Our findings suggest that Uncut Roux-en-Y may be a superior option for gastrointestinal reconstruction after laparoscopic D2 gastrectomy for distal gastric cancer., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gastric cancer (GC) is a prevalent form of cancer, with Helicobacter pylori (H. pylori) infection being the most common risk factor. Recent studies have highlighted the role of long-term irritation of the gastric mucosa caused by bile reflux in the development of cancer. Bile acids (BAs), which are a significant component in bile reflux, have the potential to promote gastric carcinogenesis through various mechanisms. These mechanisms include the induction of intestinal metaplasia (IM), inhibition of H. pylori activity, modification of H. pylori colonization, and alteration of the abundance and composition of microorganisms in the stomach. Defining the mechanism of bile acid-induced gastric carcinogenesis could potentially be an effective approach to prevent GC. Hence, this paper aims to review the mechanism of bile acid-induced IM, the association between BAs and H. pylori infection as well as microorganisms in the stomach, and the correlation between BAs and gastric carcinogenesis. The ultimate goal is to elucidate the role of BAs in the development of GC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bile reflux or duodenogastric reflux (DGR), refers to the retrograde flow of duodenal contents (mainly bile) into the stomach; capable of producing chemical damage to the mucosa, and triggering mutations towards the development of intestinal metaplasia, dysplasia and even gastric cancer., Objective: This study aimed to estimate the prevalence of primary bile reflux in cholecystectomized patients and to identify whether cholecystectomy is a risk factor for development of DGR., Materials and Methods: An analytical cross-sectional and observational study was conducted, in which all patients who underwent upper digestive endoscopy from February to June 2023 in a private endoscopic center in Lima, Peru, were included. According to the endoscopic report, patients were divided into two groups as those with DGR and those without DGR. Demographic characteristics, history of cholecystectomy, and endoscopic findings were statistically analyzed. 408 patients were included., Results: The mean age of the population was 48.18 ± 16.82 years; 61.52% were female. The prevalence of DGR was 25.74% in the population, while in cholecystectomized patients it was 52.11%. The prevalence of DRG in patients with a history of cholecystectomy was 2.58 times compared to patients without cholecystectomy (p<0.001). Age ≥50 years also behaved as a risk factor for RDG (p=0.025). No significant difference in diabetes, Helicobacter pylori infection or smoking were found., Conclusion: In conclusion, a history of cholecystectomy as well as age were found to be risk factors for development of primary DGR.

Objective: Bile reflux gastritis is caused by the backward flow of duodenal fluid into the stomach. A retrospective cohort study was performed to estimate the prevalence and risk factors of bile reflux gastritis postcholecystectomy, and to evaluate the endoscopic and histopathologic changes in gastric mucosa., Methods: Patients with refractory upper abdominal pain right below the ribs with symptoms of bloating, burping, nausea, vomiting, and bile regurgitation during the period from January 2018 to December 2020, submitted to Zagazig University Hospitals were enrolled in this study. The studied 64 patients were divided into two groups; the control group (CG): 30 subjects who had never undergone any biliary interventions, and the post-cholecystectomy group (PCG): 34 patients who had undergone cholecystectomy., Results: The prevalence of bile reflux gastritis was (16.7%) and (61.8%) in CG and PCG, respectively. Diabetes, obesity, elevated gastric bilirubin, and elevated stomach pH were all risk factors for bile reflux gastritis in both groups ( r   =   . 28,.48,.78,.57 respectively) . Age, sex, epigastric pain, heartburn, vomiting, and the existence of bile reflux gastritis, on the other hand, had no correlation., Discussion: After a cholecystectomy, bile reflux gastritis is prevalent, especially among obese and diabetic patients.

Objective: Incomplete intestinal metaplasia (IIM) of the stomach is associated with higher risk of progression to dysplasia and gastric cancer than complete intestinal metaplasia (CIM). Whether the causative factors underlying IIM are different from those underlying CIM is currently unknown. In a recent study, bile acids were found to induce gastric intestinal metaplasia (IM) in mice by activating STAT3 signaling and accelerated the development of dysplasia. The aim of this study was to determine whether there are differences in associations between IIM and CIM and clinicopathologic features known to be associated with intestinal metaplasia, bile reflux, and activated STAT3., Methods: Fifty-two consecutive gastric biopsies with IM were examined for the type of metaplasia, presence of inflammation, and Helicobacter pylori ( H. pylori ) status. Immunohistochemical staining was performed for phospho-STAT3 (p-STAT3) and evaluated by image analysis. The type of IM was then correlated with relevant clinicopathologic variables and p-STAT3 expression., Results: Seven cases had IIM only, 31 had CIM only, and 14 had both CIM and IIM (CIIM). Significantly fewer cases with IIM had chronic gastritis than either CIM or CIIM (43%, 93%, 79%, respectively, p =0.005). H. pylori was not detected in any of the IIM cases but was positive in 29% of CIM and 29% of CIIM. Fifty-seven percent of patients with IIM had a history of cholecystectomy compared to 25% of those with CIM and 23% of those with CIIM. The mean BMI was 32.3 kg/m 2 for patients with IIM compared to 28 kg/m 2 for those with CIM and 31.2 kg/m 2 for those with CIIM. Median p-STAT3 for biopsies with was IIM was 6.36 compared to 3.54 for CIM and 6.27 for CIIM. Reactive gastropathy was present in 57% of biopsies with IIM, 39% of CIM and 50% of CIIM., Conclusion: In contrast to CIM, IIM is significantly less likely to be associated with chronic gastritis. CIIM also tended to be less associated with H. pylori infection and more associated with reactive gastropathy, history of cholecystectomy, higher BMI, and higher median p-STAT3. These results tend to suggest that IIM is probably more likely to be associated with bile reflux than H. pylori -associated gastritis. Larger studies are needed to confirm these findings.Presented in part at Digestive Disease Week 2023, Chicago, IL, May 6, 2023., (© 2023 by the Association of Clinical Scientists, Inc.)

Background. Single anastomotic surgeries can increase the risk of reflux, marginal ulceration, and gastrointestinal complications. Braun anastomosis prevents bile reflux after gastric resection and gastrojejunal anastomosis surgeries. The present pilot study evaluated Braun's efficacy in a single anastomosis sleeve ileal (SASI) bypass surgery. Methods. 28 patients with a history of SASI bypass surgery from October 2017 to September 2021 were included in the study. Patients were divided into 2 groups based on having Braun anastomosis to this surgical procedure; group A: underwent SASI bypass without Braun anastomosis; group B: underwent SASI bypass with Braun anastomosis. The surgical complications in terms of bile reflux, marginal ulcer, reflux esophagitis, and gastritis were evaluated and compared between the groups. Results. Bile reflux and reflux esophagitis were seen more in group A than in group B (37.5% vs 8.3% and 18.8% vs 8.3%, respectively). In contrast, 2 patients (16.7%) in group B had marginal ulcers compared to 1 (6.3%) in group A. Also, gastritis was seen in 1 patient in each group (6.3% in group A vs 8.3% in group B). However, the differences were not statistically different. Conclusions. Braun anastomosis is probably an effective procedure to reduce bile reflux, a concern of SASI bypass. Besides, further studies with a larger study population are needed.

Background: Traditional Roux-en-Y may cause Roux-en-Y stasis syndrome (RSS), and Uncut Roux-en-Y was proposed to solve this problem. However, because afferent loop recanalization may occur after surgery, its clinical application remains controversial. The purpose of this study was to compare the long-term outcomes of these two gastrointestinal reconstruction methods., Methods: A total of 108 patients who received laparoscopic-assisted distal gastrectomy (LADG) were enrolled; 57 were randomly divided into the Uncut Roux-en-Y (URY) group, and 51 were divided into the Roux-en-Y (RY) group. Patients were followed up for 1 year to evaluate variables, including the following: (1) Assessments for RSS; (2) Preoperative and postoperative Gastrointestinal Symptom Rating Scale (GSRS) scores; (3) Postoperative gastroscopy to assess the occurrence of reflux esophagitis (Los Angeles classification), residual gastritis and bile reflux 1 year after surgery; and (4) Upper gastrointestinal radiography to evaluate whether recanalization occurred in patients in the URY group after surgery., Results: At 1 year after surgery, a total of 42 patients (73.7%) developed afferent loop recanalization. The incidence of RSS was not different between the two groups (OR, 1.301 [95% CI, 0.482 to 3.509]; P = 0.603P = 0.603). The GSRS score was higher in the URY group (P < 0.001). Postoperative gastroscopy showed that the incidence of bile reflux (P < 0.001) and the grade of residual gastritis (P < 0.001) were significantly higher in the URY group, but the grade of reflux esophagitis was not significantly different (P = 0.447, [95% CI, 0.437 to 0.457]P = 0.397)., Conclusions: Compared with traditional Roux-en-Y anastomosis, due to the high recanalization rate, the URY group developed more severe gastrointestinal symptoms, the incidence of bile reflux and the grade of residual gastritis increased and the incidence of postoperative RSS was not reduced., (© 2023. The Author(s).)

Background: Vagus nerve-preserving gastrectomy is increasingly popular in treating gastric cancer in the early stage, however the long and short-term outcomes after gastrectomy while preserving the celiac branch of the vagus nerve are not well defined. We aimed to summarize and compare perioperative and longer-term outcomes after celiac branch vagus nerve-preserving gastrectomy (CBP, preserving both the celiac and hepatic branches of the vagus nerve), compared to those without CBP (non-CBP, only the hepatic branch of the vagus nerve is preserved)., Methods: We searched the Embase, PubMed, Cochrane Library and Web of Science databases for papers published before October 2021. The primary results were evaluated by short-term and long-term postoperative complications, whereas the secondary outcomes included surgery-related parameters, recovery-related parameters and overall survival. Random-effects or fixed-effects model were used to estimate odds ratio, and weighted mean difference for the outcomes. The underlying publication bias was identified via funnel charts, Begg's test and Egger's test. Sensitivity analysis was conducted by removing the research one by one., Results: A total of 9 studies consisting of 8 retrospective studies and one randomized control trial were included. The analysis included 1,109 patients, with 568 (51.2%) of patients receiving CBP and 541 (48.8%) patients who received non-CBP. The CBP group had a shorter time in terms of first flatus (weighted mean difference = -0.436, 95% confidence interval: -0.603 to -0.269; P < 0.001) and hospital stay (weighted mean difference = -0.456, 95% confidence interval: -0.874 to -0.037, P = 0.033) than the non-CBP group, but the time to the start of oral intake was comparable between the groups. Regarding short-term complications and surgery-related parameters, between CBP and non-CBP, no evident differences were observed in pancreatic complications, anastomotic leakage, postoperative bleeding, operation time, blood loss or lymph nodes examined. In terms of long-term complications, the incidence of gallstones in CBP was lower than that in non-CBP (odds ratio = 0.582, 95% confidence interval: 0.356-0.953, P = 0.031), and the incidence of bile reflux in CBP was lower than that in non-CBP (odds ratio = 0.473, 95% confidence interval: 0.280-0.800, P = 0.005). However, the prevalence rates of diarrhea, early dumping syndrome, esophageal reflux, and delayed gastric emptying were comparable between CBP and non-CBP., Conclusion: The present research showed that gastric cancer patients in the early stage under CBP were superior to those without CBP in terms of incidence of gallstones, bile reflux, time of first flatus and hospital stay. Furthermore, it is imperative to conduct randomized control studies with larger sample sizes to determine the oncological survival outcomes when preserving the celiac branch., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: There are a few articles to study the relationship between bile reflux gastritis (BRG) and H. pylori infection, and the results are debatable. This study set out to determine the relationship between BRG and Helicobacter pylori ( H. pylori ) infection., Methods: In this retrospective study, patients from January, 1st 2013 to January, 1st, 2021 were divided into two groups based on whether they had BRG. The control group was got by 1:1 propensity-score matching (PSM) based on age and sex. Then, the relationship between BRG and H. pylori in patients was analyzed via Chi-squared test and Phi (φ) detection., Results: 26449 patients were included in this study, and there were 1918 patients in each group after age and sex matching. patients with HP were responsible for 35% (9345/26449) and patients with BRG were 7% (1918/26449). Further relationship exploration, there is a negative, but weak, the relationship between BRG and HP infection ( X 2 = 45.62, p  < .001, Phi (φ)= -0.109)., Conclusion: Patients with bile reflux may have less likely to get HP infection. HP eradication is an important thing for the prevention of gastric cancer and this study serves as a foundation and may provide directions for future research.

Background: Bile reflux can cause inflammation, gastric mucosa atrophy, and diseases such as stomach cancer. Alkaline bile flowing back into the stomach affects the intragastric environment and can alter the gastric bacterial community. We sought to identify the characteristics of the stomach mucosal microbiota in patients with bile reflux., Methods: Gastric mucosal samples were collected from 52 and 40 chronic gastritis patients with and without bile reflux, respectively. The bacterial profile was determined using 16S rRNA gene analysis., Results: In the absence of H. pylori infection, the richness (based on the Sobs and Chao1 indices; P <0.05) and diversity (based on Shannon indices; P <0.05) of gastric mucosa microbiota were higher in patients with bile reflux patients than in those without. There was a marked difference in the microbiota structure between patients with and without bile reflux (ANOSIM, R=0.058, P=0.011). While the genera, Comamonas , Halomonas , Bradymonas , Pseudomonas , Marinobacter , Arthrobacter , and Shewanella were enriched in patients with bile reflux, the genera, Haemophilus , Porphyromonas , and Subdoligranulum , were enriched in those without bile reflux., Conclusion: Our results demonstrate that bile reflux significantly alters the composition of the gastric microbiota., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Huang, Wang, Wang, Tian, Yu, Zuo and Li.)

Abstract: Gastric intestinal metaplasia (GIM) is a precancerous lesion of gastric cancer (GC) and is considered an irreversible point of progression for GC. Helicobacter pylori infection can cause GIM, but its eradication still does not reverse the process. Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa, and bile acids in refluxed fluid have been widely reported to be associated with GIM. This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: The number of mini gastric bypass / one anastomosis bypass (MGB-OAGB) procedures in bariatric patients that have been performed world-wide has drastically increased during the past decade. Nevertheless, due to the risk of subsequent biliary reflux and development of ulcer and neoplastic (pre)lesions caused by long-time bile exposure, the procedure is still controversially discussed. In here presented case report, we could endoscopically demonstrate a transformation from reflux oesophagitis to Barrett's metaplasia most likely caused by bile reflux after mini-gastric bypass. To our knowledge, this is a first case study that shows development of Barrett's metaplasia after MGB-OAGB., Case Presentation: We present the case of a 50-year-old female which received a mini-gastric bypass due to morbid obesity (body mass index (BMI) 42.4 kg/m 2 ). Because of history gastroesophageal reflux disease (GERD), a fundoplication had been performed earlier. Preoperative gastroscopy showed reflux esophagitis (Los Angeles classification grade B) with no signs of Barrett's metaplasia. Three months post mini-gastric bypass, the patient complained about severe bile reflux under 40 mg pantoprazole daily. Six months postoperative, Endoscopically Barrett's epithelium was detected and histopathologically confirmed (C1M0 after Prague classification). A conversion into Roux-en-Y gastric bypass was performed. The postoperative course was without complications. In a follow up after 6 months the patient denied reflux and showed no signs of malnutrition., Conclusions: The rapid progress from inflammatory changes of the distal esophagus towards Barrett's metaplasia under bile reflux in our case is most likely a result of previous reflux disease. Nevertheless, bile reflux appears to be a potential decisive factor. Study results regarding presence of bile reflux or development of endoscopically de-novo findings after MGB-OAGB are widely non-conclusive. Long-term prospective studies with regular endoscopic surveillance independent of clinical symptoms are needed., (© 2022. The Author(s).)

Purpose: Esophagectomy with gastric tube reconstruction is often complicated postoperatively by duodenogastric reflux and/or delayed gastric emptying and the accompanying symptoms, leading to patients being dissatisfied with their quality of life (QOL). Medical interventions to relieve patients of their symptoms are rarely effective. We began, in 2018, performing double tract-like gastric tube reconstruction, and, in a pilot study, we compared postoperative QOL between patients in whom this experimental reconstruction was performed and those in whom conventional reconstruction was performed., Methods: Included in the study were 33 patients who underwent thoracoscopic McKeown esophagectomy with two- or three-field lymph node dissection for thoracic esophageal cancer between April 2015 and March 2020. A gastric tube about 4 cm in width was created in all patients, and in 14 of the patients (DT group), a double tract was appended by anastomosing the elevated jejunum to the anterior wall of the gastric tube, QOL was assessed 10-14 months later by means of the DAUGS-32 questionnaire, and bile reflux and the presence or absence of food residue were assessed by upper gastrointestinal endoscopy., Results: DAUGS-32 food passage dysfunction, nausea and vomiting, and reflux symptoms scores were significantly lower in the DT group than in the conventional reconstruction group. There was no significant between-group difference in the incidence of postoperative complications. No food residue was seen in DT patients' gastric tube, and no reflux esophagitis was observed., Conclusion: Double tract-like gastric tube reconstruction shows promise as an effective means of improving patients' post-esophagectomy QOL., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL-6), lipopolysaccharide (LPS), and the relative abundance of LPS-producing bacteria are increased significantly in the gastric juice of both BRG and GC patients. A secondary BA, taurodeoxycholic acid (TDCA), is significantly and positively correlated with the LPS-producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES-1) through activation of the IL-6/JAK1/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS-producing bacteria (Prevotella melaninogenica), respectively, and the other by bile reflux (BR) surgery, mimicking clinical bile refluxing. Moreover, the bile reflux induced gastric precancerous lesions observed in the post BR surgery mice can be prevented by treatment with cryptotanshinone, a plant-derived STAT3 inhibitor. These results reveal an important underlying mechanism by which bile reflux promotes gastric carcinogenesis and provide an alternative strategy for the prevention of GC associated with BRG., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Purpose: Excellent metabolic improvement following one anastomosis gastric bypass (OAGB) remains compromised by the risk of esophageal bile reflux and theoretical carcinogenic potential. No 'gold standard' investigation exists for esophageal bile reflux, with diverse methods employed in the few studies evaluating it post-obesity surgery. As such, data on the incidence and severity of esophageal bile reflux is limited, with comparative studies lacking. This study aims to use specifically tailored biliary scintigraphy and upper gastrointestinal endoscopy protocols to evaluate esophageal bile reflux after OAGB, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB)., Methods: Fifty-eight participants underwent OAGB (20), SG (15) or RYGB (23) between November 2018 and July 2020. Pre-operative reflux symptom assessment and gastroscopy were performed and repeated post-operatively at 6 months along with biliary scintigraphy., Results: Gastric reflux of bile was identified by biliary scintigraphy in 14 OAGB (70%), one RYGB (5%) and four SG participants (31%), with a mean of 2.9% (SD 1.5) reflux (% of total radioactivity). One participant (OAGB) demonstrated esophageal bile reflux. De novo macro- or microscopic gastroesophagitis occurred in 11 OAGB (58%), 8 SG (57%) and 7 RYGB (30%) participants. Thirteen participants had worsened reflux symptoms post-operatively (OAGB, 4; SG, 7; RYGB, 2). Scintigraphic esophageal bile reflux bore no statistical association with de novo gastroesophagitis or reflux symptoms., Conclusion: Despite high incidence of gastric bile reflux post-OAGB, esophageal bile reflux is rare. With scarce literature of tumour development post-OAGB, frequent low-volume gastric bile reflux likely bears little clinical consequence; however, longer-term studies are needed., Clinical Trial Registry: Australian New Zealand Clinical Trials Registry number ACTRN12618000806268., (© 2022. Crown.)

Background: One anastomosis gastric bypass (OAGB) is now a mainstream bariatric procedure. Refractory gastroesophageal reflux is a significant complication following OAGB, and conversion to Roux-en-Y has long been the treatment of choice for this issue. Strengthening the lower esophageal sphincter by Nissen fundoplication (NF) has been reported as an effective anti-reflux surgery. Here we report the short-term outcomes of a modified NF procedure using the excluded stomach (excluded stomach fundoplication-ESF) to treat refractory bile reflux in post-OAGB patients., Methods: Thirteen post-OAGB patients underwent ESF for refractory bile reflux during the study, as detailed in the surgical technique. This paper reports the 12 patients whose follow-up data are available., Results: Following ESF, the GERD-HRQL heartburn score improved from 22.7 ± 3.9 to 1.8 ± 3.5 (p < 0.05). The mean aggregate GERD-HRQL score improved from 27.9 ± 5.3 to 5.7 ± 5.9 (p < 0.05). The GERD-HRQL global satisfaction score showed that 100% of patients were satisfied with the improvement of symptoms. The mean VISICK score improved from 3.8 ± 0.39 to 1.2 ± 0.39 (p < 0.05). One patient was returned to the operating theatre to have the wrap loosened due to dysphagia. Eleven patients did not require PPIs after surgery., Conclusions: ESF significantly improved the VISICK score and GERD-HRQL of post-OAGB patients with refractory bile reflux in the short term. The current study is being continued to increase the sample size and the follow-up period., (© 2021. The Author(s).)

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Biliary gastropathy is a disease characterized by upper abdominal pain, frequent heartburn, nausea, and vomiting of bile. It is caused by the backward flow of duodenal fluid into the stomach and esophagus.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; A retrospective cohort study was performed to estimate the prevalence and risk factors of bile reflux gastritis secondary to cholecystectomy and to evaluate the endoscopic and histopathologic changes in gastric mucosa caused by bile reflux gastritis.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Materials and methods:&lt;/b&gt; The study involved 64 patients with epigastric pain and/or dyspeptic symptoms during the period from January 2018 to December 2020 who presented to Zagazig University Hospitals. The subjects were divided into two groups: the control group (CG), with 30 subjects who had never undergone any biliary interventions, and the post-cholecystectomy group (PCG), consisting of 34 patients who had undergone cholecystectomy.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; The prevalence of bile reflux gastritis was 16.7% in the CG and 61.8% in the PCG. In both groups, diabetes, obesity, increased gastric bilirubin, and increased gastric pH were risk factors for bile reflux gastritis (r = 0.28, 0.48, 0.78, and 0.57, respectively). However, there were no correlations between age, sex, epigastric pain, heartburn, vomiting, and the presence of bile reflux gastritis.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Discussion:&lt;/b&gt; Bile reflux gastritis is a common complication following cholecystectomy and is more common among obese and diabetic patients.&lt;/br&gt.

Objectives: Although laparoscopic distal gastrectomy has been widely used for distal gastric cancer, the best functional reconstruction type has not yet been established. Based on previous experience, we propose a modified uncut Roux-en-Y anastomosis. This study aimed to compare the outcomes of different intracorporeal anastomoses after laparoscopic distal gastrectomy., Methods: From April 2015 to August 2020, the data of 215 patients who underwent laparoscopic distal gastrectomy was collected. The patients were divided into 4 groups according to the digestive tract reconstruction method, Billroth-I, Billroth-II, Roux-en-Y, and the modified uncut Roux-en-Y. Clinicopathologic characteristics, surgery details, short-term outcomes, and postoperative nutritional status were analyzed., Results: The operation time of Billroth-I anastomosis was significantly shorter (216.2 ± 25.8 min, P < .001) than that of other methods. There was no difference in postoperative complications and OS among the 4 reconstruction methods. The incidences of esophagitis, gastritis, and bile reflux were significantly lower in the Roux-en-Y and uncut Roux-en-Y group (P < .001) 1 year after surgery. And the postoperative albumin and PNI levels in uncut Roux-en-Y group were higher than those in other groups(P < .05). On multivariate analysis, age and reconstruction type were independently related to esophagitis, gastritis, and bile reflux. Serum albumin and the prognostic nutritional index were significantly higher in the uncut Roux-en-Y group than other groups (P < .05)., Conclusions: All 4 reconstruction techniques are feasible and safe. The Roux-en-Y and uncut Roux-en-Y are superior to Billroth-Ⅰ and Billroth-Ⅱ+Braun in terms of reflux esophagitis, gastritis, and bile reflux. Uncut Roux-en-Y may result in better PNI than the others.

Introduction: Helicobacter pylori eradication is expected to significantly change the prevalence of Barrett's esophagus (BE). However, few reports on this relationship exist. We analyzed the risk factors of BE using the current consensus on length of BE considering H. pylori infection status., Methods: We analyzed 10,122 individuals (5,962 men; mean age = 52.9 ± 9.9 years) who had undergone esophagogastroduodenoscopy as part of a medical checkup. Correlations among factors including H. pylori infectious status, endoscopic findings, and BE ≥1 cm were analyzed., Results: Prevalence of BE, long-segment BE, and esophageal adenocarcinoma was 22.5%, 0.014%, and 0%, respectively. Logistic regression analysis showed that the risk factors for BE were hiatal hernia (odds ratio [OR]: 2.89 [2.59-3.24]), female sex (OR: 0.52 [0.46-0.59]), social drinking (OR:0.77 [0.68-0.87]), H. pylori eradication therapy (OR: 1.34 [1.19-1.51]), proton pump inhibitor (PPI) use (OR: 1.52 [1.18-1.96]), bile reflux (OR: 1.18 [1.04-1.33]), age ≥50 years (OR: 1.13 [1.02-1.26]), and nonsteroidal anti-inflammatory drug (NSAID) use (OR: 1.29 [1.02-1.62]). Although reflux esophagitis (RE) was more common in H. pylori-negative patients (17.2%) than in those after H. pylori eradication therapy (11.8%, p < 0.00001), the latter was correlated with BE, disputing RE as a strong risk factor for BE. Therefore, we conducted a subgroup analysis; most of the risk factors except for PPI use (p = 0.75), H2-receptor antagonist use (p = 0.078), and atrophic gastritis absence (p = 0.72) were positively correlated with BE after H. pylori eradication therapy compared with H. pylori-negative status., Conclusions: H. pylori eradication, bile reflux, PPI use, and NSAID use were risk factors for BE along with hiatal hernia, male sex, and older age., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Chronic abdominal pain is a frequent childhood complaint. This study aims to determine the relationship between bile reflux, which is increasing with the growth in packaged food consumption resulting from the changing food industry, and Helicobacter pylori gastritis., Methods: In this retrospective study, 804 cases where there was an endoscopic examination for abdominal pain were included. We recorded the patients` age, sex, and macroscopic and microscopic endoscopic findings. Patients with chronic diseases were excluded., Results: Our study included 804 cases. Of patients, 61.8% were female and 38.2% were male. The mean age was 11.56±4.14 years. The Helicobacter pylori gastritis rate was found to be 22.3% among all patients. Bile reflux was seen in 192 (23.9%) patients. Only 27 (14.1%) of the 192 patients had Helicobacter pylori positivity (p=0.002)., Conclusions: Helicobacter pylori gastritis is less common among patients with bile reflux. In another study conducted in our outpatient clinic before the 2000s, the frequency of Helicobacter pylori gastritis was found to be 40%, but after 2000 this rate decreased to 22.3% due to bile reflux caused by the changing food industry. This result may be explained by the bactericidal effects of bile acids.

Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are frequently present in the gastroesophageal refluxate and their effect has been associated with inflammatory and neoplastic changes in the upper aerodigestive tract. Recent in vitro and in vivo studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NF‑κB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting anti‑apoptotic effects and causing precancerous lesions. The most important findings that strongly support bile reflux as an independent risk factor for hypopharyngeal cancer are presented in the current review and the underlying mechanisms are provided.

Increasing evidence suggests that bile reflux (BR) plays a major role in mucosal injury, leading to adenocarcinoma of the proximal stomach and distal esophagus. However, gastric BR is difficult to diagnose and investigate. Reactive gastropathy (RG), in the absence of nonsteroidal anti-inflammatory drugs (NSAIDs) and other known causes, likely represents bile-mediated injury to the gastric mucosa. The goal of this study is to explore the association between antral RG and gastroesophageal junction (GEJ) mucosal inflammation and intestinal metaplasia (IM). The pathology database was searched for patients who had gastric biopsies with a diagnosis of antral RG and concurrent gastric cardia/GEJ/distal esophagus biopsies from 2013 to 2015. Age- and sex-matched patients with normal gastric antral biopsies served as controls. Biopsies from the GEJ region were evaluated for histological changes, including inflammation, antral and pancreatic metaplasia, RG, the type of gastric glands, proton pump inhibitor (PPI) changes, and IM. Detailed clinical history and medication use (including PPIs and NSAIDs) were recorded. IM in the GEJ region was more frequent in patients with antral RG than in controls (33.0% vs. 5.2%, 95% confidence interval [18.3-37.3%]). In addition, inflammation, other mucosal changes around the GEJ (RG and foveolar hyperplasia), antral IM, and PPI-associated mucosal changes were also more frequently seen in patients with antral RG. Our results show that antral RG is associated with mucosal injury and IM around GEJ, suggesting a role of BR. Further studies are needed to study duodenogastric-esophageal BR and its role in development of proximal gastric and distal esophageal adenocarcinoma., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To evaluate the relationship between gastric cancer (GC) and precancerous lesions and bile reflux., Methods: Medical records of 30 465 participants who underwent gastroscopy between January and December 2018 in our center were reviewed. Their age, sex, time of endoscopy, endoscopic/histologic diagnosis and grade of bile reflux were recorded. The participants were further divided into the chronic gastritis group (n = 27 807), a precancerous lesion group (n = 1943) and a GC group (n = 715). The χ 2 tests and hierarchical analyses were performed., Results: Patients aged 18-27 years had a higher bile reflux rate than those aged 28-37 and 68-75 years (P < 0.001), while it did not differ between patients aged <50 years and those over 50 years (P = 0.639). It was lower in men than in women (P < 0.001). The bile reflux rate did not differ in terms of months, seasons and half of the year (all P > 0.05), but differed between morning and afternoon when they underwent the endoscopy (P = 0.000). There was an interrelationship between the severity of gastric mucosal disease and bile reflux grade (r = 0.171). After excluding the effects of sex, age and time of endoscopy on bile reflux, bile reflux rate in chronic gastritis and precancerous lesions was lower than in gastric cancer (P < 0.01)., Conclusions: Bile reflux may be a risk factor for gastric cancer and precancerous lesions. A high grade of bile reflux may be associated with the progression of gastric mucosal diseases., (© 2020 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Objectives: Although there are many studies that investigate the relationship between duodenogastric reflux (DGR) and Helicobacter pylori in adult patients, the reported data are contradictory. In addition, there are very few studies in the literature investigating the relationship between DGR and H.pylori in the pediatric age group. In the present study, we investigated the effect of primary DGR on H.pylori and gastritis. Materials and Methods: A total of 361 patients who were referred to the clinic of our hospital with dyspeptic complaints who had an upper gastrointestinal system endoscopy and a gastric biopsy were included in the study. Results: DGR was detected in 45 cases, and 316 cases that did not have DGR were considered as the control group. Comparisons were made between the DGR cases and the control group in terms of risk factors (age, gender), the presence and density of H.pylori , and the presence and severity of gastritis. The average age of the patients who were included in the study was 11.6 ± 4.6 years. A total of 128 (36%) of the cases were male and 233 (64%) were female. DGR was present in 45 (13%) of the cases. The average age of the patients with DGR was 13.9 ± 3.1 years, the average age of the control group was 11.3 ± 4.7, and there were statistically significant differences ( p < 0.001). No significant differences were detected in terms of gender between DGR and the control group ( p > 0.05). H.pylori (+) was detected in 29 (64%) of patients with DGR, and in 202 (64%) of the control group. No significant differences were detected between H.pylori prevalence ( p = 0.947). Gastritis was detected in 37 (82%) of the patients with DGR, and in 245 (77%) of the control group ( p = 0.476). No significant differences were detected between the presence and density of H.pylori , gastritis presence, severity and DGR ( p > 0.05). Conclusions: The ages of patients with DGR were significantly higher than in the control group, and advanced age was shown to be a risk factor for primary DGR. It was found that the presence of DGR has no effect on the presence and severity of H.pylori . Given this situation, we consider it is important to eradicate H.pylori infection, especially in the case where H.pylori is present together with DGR.

Background: Recent preclinical explorations strongly support the tumorigenic potential of bile on laryngopharyngeal mucosa. Herein, the authors describe, in bile-related human hypopharyngeal squamous cell carcinoma (HSCC), NF-κB-related messenger RNA (mRNA) and microRNA (miRNA) oncogenic phenotypes similar to those previously identified in acidic bile-exposed premalignant murine hypopharyngeal mucosa., Methods: In this pilot study, the authors included human HSCC specimens paired with their adjacent normal tissue (ANT) derived from 3 representative patients with documented biliary laryngopharyngeal reflux (bile[+]) compared with 5 control patients without signs of bile reflux disease (bile[-]). Immunohistochemical, quantitative polymerase chain reaction, and miRNA analyses were used to detect the levels of activated NF-κB and expression levels of STAT3, EGFR, BCL2, WNT5A, IL-6, IL-1B, ΔNp63, cREL, TNF-α, TP53, NOTCH1, NOTCH2, NOTCH3, miR-21, miR-155, miR-192, miR-34a, miR-375, miR-451a, miR-489, miR-504, and miR-99a., Results: Bile(+) HSCC demonstrated an intense NF-κB activation accompanied by significant overexpression of RELA(p65), EGFR, STAT3, BCL-2, cREL, ΔNp63, WNT5A, IL-6, and IL1B; upregulation of oncomir miR-21; and downregulation of tumor suppressor miR-375 compared with their respective ANTs. Bile(+) HSCC demonstrated significantly higher mRNA levels of all the analyzed genes, particularly RELA(p65), IL-6, EGFR, and TNF-α compared with bile(-) tumors. The miR-21/miR-375 ratio, which previously has been linked to tumor aggressiveness, was found to be >260-fold and >30-fold higher, respectively, in bile(+) HSCCs compared with their ANTs and bile(-) tumors., Conclusions: Although limitations apply to this pilot study due to the small number of patients with HSCC, the novel findings suggest that a history of bile as a component of esophageal reflux disease may represent an independent risk factor for hypopharyngeal carcinogenesis., (© 2019 American Cancer Society.)

Rationale: Gastritis cystica profunda (GCP) is a rare gastric lesion involving cystic dilation of the gastric glands extending into the submucosa. It is usually observed at anastomotic sites in the stomach of patients who have undergone gastric procedures. Bile reflux GCP is rare in patients who have not undergone gastric surgery. Here, we report a rare case of a patient with GCP associated with bile reflux, who had no history of gastric surgery., Patient Concerns: A 50-year-old man presented with intermittent abdominal fullness for 2 years, along with nausea. He had never undergone gastric surgery. Endoscopic ultrasonography (EUS) showed a thickened gastric wall and an echo-poor submucosal layer of the gastric fundus. A 3 cm × 2 cm × 1.5 cm lesion was noted., Diagnosis: Bile reflux GCP INTERVENTIONS:: Endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection (ESD) were performed, and the lesion was removed. Conventional pathological examination revealed GCP with glands hyperplasia and a yellow-brown deposit, which was considered bile. The findings were consistent with a diagnosis of GCP without malignancy., Outcomes: Upper gastrointestinal barium meal revealed postoperative changes at the gastric fundus. Gastroscopy performed at 6 months after surgical resection showed superficial gastritis with bile reflux., Lessons: The findings suggest that GCP etiology varies and that GCP can be caused by bile reflux but without malignancy. Additionally, GCP is not limited to patients who have previously undergone gastric surgery. Moreover, it is difficult to identify. EUS and ESD might be good approaches for the diagnosis and treatment of GCP.

Introduction: Laparoscopic single anastomosis gastric bypass (SAGB) is increasingly performed for morbidly obese patients., Aim of Work: This pilot study aims primarily at evaluating the incidence of bile gastritis after SAGB. The occurrence of reflux oesophagitis and reflux symptoms were also assessed., Patients and Methods: This study included 20 patients having no reflux symptoms. All patients underwent a SAGB as a primary bariatric procedure by a single surgeon. Patients included consented to have an upper GI endoscopy done at 6 months postoperatively. Gastric aspirate was sent for bilirubin level assessment. Gastric and esophageal biopsies were submitted for histopathology and campylobacter-like organism (CLO) test., Results: In our study, the rate of bile gastritis was 30%. In 18 patients, the level of bilirubin in gastric aspirate seems to be related to the degree of mucosal inflammation. The remaining two patients had microscopic moderate to severe gastritis with normal aspirate bilirubin level. Two patients with bilirubin level in aspirate more than 20 mg/dl had severe oesophagitis, gastritis with erosions, and metaplasia. Relationship between bilirubin level and histopathological findings of gastric biopsy examination was statistically significant with a P value of 0.001., Conclusion: The incidence of bile gastritis in this cohort is higher than reported in the literature, and this may be worrying. The correlation between endoscopic findings and patients' symptoms is poor. Bilirubin level and pH in aspirate might be useful tools to confirm alkaline reflux. Its level might help to choose candidates for revision surgery after SAGB. This needs further validation with larger sample size.

Background: Gastric stump carcinoma is an exceptional and poorly known long-term complication after pancreaticoduodenectomy., Cases Presentation: Two patients developed gastric stump carcinoma 19 and 10 years after pancreaticoduodenectomy for malignant ampulloma and total pancreaticoduodenectomy for pancreatic adenocarcinoma, respectively. Both patients had pT4 signet-ring cell carcinoma involving the gastrojejunostomy site that was revealed by bleeding or obstruction. Patient 1 is alive and remains disease-free 36 months after completion gastrectomy. Patient 2 presented with peritoneal carcinomatosis and died after palliative surgery. We identified only 3 others cases in the English literature., Conclusions: Prolonged biliary reflux might be the most important risk factor of gastric stump carcinoma following pancreaticoduodenectomy. Its incidence might increase in the future due to prolonged survival observed after pancreaticoduodenectomy for benign and premalignant lesions.

Objective: This study aimed to evaluate the relationship between biliary excreted contrast media in the stomach and the presence of bile reflux gastritis., Methods: Consecutive 111 patients who underwent both gadoxetic acid-enhanced magnetic resonance cholangiography (gadoxetic MRC) and gastric endoscopy were included in this study. We performed a review of the gadoxetic-MRC image sets acquired 60 minutes after intravenous injection of contrast media and endoscopic images. We recorded amount of contrast media in the stomach. The sensitivity, specificity, and accuracy of duodenogastric bile reflux diagnosis were evaluated for the gadoxetic MRC. Statistical analysis was performed using the Fisher exact test and the linear-by-linear association test., Results: Among the 111 patients, 39 had 60-minute delayed images showing the presence of contrast media in the stomach. Of these 39 patients, 13 had bile reflux gastritis and 5 showed bile in the stomach without evidence of erythematous gastritis. Of the 72 patients who did not show contrast media in the stomach, none had bile reflux gastritis and 2 patients showed bile staining in the stomach without evidence of erythematous gastritis. Bile reflux gastritis was significantly more frequent in patients with contrast media in the stomach on gadoxetic MRC than in those without. Patients with high-grade extension of contrast media in the stomach had significantly frequent bile reflux gastritis than did those with low-grade extension., Conclusion: Biliary excreted contrast media in the stomach on 60-minute delayed gadoxetic MRC has a correlation with the presence of bile reflux gastritis on endoscopic examination.

Background: Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC., Methods: Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated., Results: Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors., Conclusions: Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Barrett's esophagus (BE) is a well-recognized precursor of esophageal adenocarcinoma (EAC) and is defined as ≥1 cm segment of salmon-colored mucosa extending above the gastroesophageal junction into the tubular esophagus with biopsy confirmation of metaplastic replacement of the normal squamous epithelium by intestinal-type columnar epithelium. The incidence of both BE and EAC has been increasing over the past few decades. As a result, preventing the development of BE by identifying and understanding its modifiable and non-modifiable risk factors may help reduce the incidence of EAC. Over the recent past, a tremendous amount of progress has been made towards improving our knowledge of risk factors and pathogenesis of BE. This article reviews the evidence for the various risk factors for developing BE., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Stone recurrence is a common late adverse event after ERCP in patients with common bile duct stones (CBDS). Duodenal-biliary reflux (DBR) is considered a major cause of CBDS recurrence. However, specific evidence is still lacking., Objective: To investigate the DBR rate in patients with recurrent CBDS after ERCP., Design: A prospective case-control study., Setting: A tertiary center., Patients: During follow-up, patients with a history of either recurrent CBDS (recurrence group) or nonrecurrent CBDS (control group) were invited to participate in the study. All patients had previously undergone successful CBDS removal by ERCP. Patients in the control group were matched with the recurrence group by age and gender in a 1:1 ratio. Patients with gallbladder stones, hepatolithiasis, remnant CBDS, CBD strictures, or stents were excluded., Interventions: Standard barium meal examination, MRCP, and enhanced abdominal CT., Main Outcome Measurements: DBR., Results: Thirty-two patients with a history of recurrent CBDS and 32 matched control subjects were enrolled. Baseline characteristics and parameters regarding the first ERCP were comparable between the 2 groups. The DBR rate was significantly higher in the recurrent than in the control group (68.8% vs 15.6%, P < .001). Multivariate analysis indicated that DBR (OR, 9.59; 95% CI, 2.65-34.76) and acute distal CBD angulation (OR, 5.48; 95% CI, 1.52-19.78) were independent factors associated with CBDS recurrence. DBR rates in patients with no, single, or multiple recurrences were 15.6%, 60.9%, and 88.9%, respectively (P < .001). Intrahepatic bile duct reflux was more common in patients with multiple recurrences., Limitations: Small sample size., Conclusions: DBR is correlated with CBDS recurrence in patients who had previously undergone ERCP. DBR and acute distal CBD angulation are 2 independent risk factors related to stone recurrence. (, Clinical Trial Registration Number: NCT02329977.), (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Context: Gastroesophageal reflux disease (GERD) is a common complication in the spinal cord injury (SCI) population. Surgical treatment of GERD has a unique risk/benefit profile in this population., Findings: This 68-year-old male with chronic incomplete tetraplegia, dyslipidemia, and well-controlled diabetes mellitus underwent Roux-en-Y gastric bypass surgery (RYGBP) for intractable biliary reflux. Postoperatively, the patient had resolution of his symptoms but he also presented with significant weight loss and dumping syndrome. While he did have improvement in his dyslipidemia there was no change in his functional status., Conclusions: RYGBP is an option for refractory GERD treatment in the SCI population but preoperative risk assessment and close monitoring postoperatively is essential.

Objective: To determine the prevalence of biliopancreatic reflux (BPR) in patients with biliary pancreatitis (BP) undergoing elective cholecystectomy with intraoperative cholangiography (IOC) in comparison with a control group of symptomatic cholelithiasis (CG)., Patients and Methods: Retrospective review of 107 consecutive BP cases. BPR was determined by IOC and liver function tests (LFT) were recorded at admission (A), 48hours, and preoperative examination (P). LFT analysis between A and P were analysed between groups with respect to BPR, time interval to cholecystectomy within the same group and by determination of observed value/maximum normal value ratio (OV/MNV)., Results: BPR incidence was 38.3% in BP in comparison with 5% in CG (p=0.0001) it was independent from interval time to cholecystectomy, in contrast with Odditis, suggesting an anatomical condition for CCBP and a functional one for Odditis. LFT analysis showed no differences in relation to BPR incidence. LFT excluding AP and GGT returned to normal values with significant differences in OV/MNV when BPR was present which points to an increased cholestasis in BPR group. US dilatation of CBD was noted in 10.3% and was associated to CCBP., Conclusions: BPR in BP increases cholestasis and contributes to confusion in the estimation of common bile duct stones increasing ERCP-EE rates. US and biochemical markers of CBDS show a low specificity due to BPR-CCBP which suggests that MRI-cholangiography is a mandatory exploration before ERCP-EE examination., (Copyright © 2012 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Oesophageal exposure to duodenogastroesophageal refluxate is implicated in the development of Barrett's metaplasia (BM), with increased risk of progression to oesophageal adenocarcinoma. The literature proposes that reflux exposure activates NF-κB, driving the aberrant expression of intestine-specific caudal-related homeobox (CDX) genes. However, early events in the pathogenesis of BM from normal epithelium are poorly understood. To investigate this, our study subjected a 3D model of the normal human oesophageal mucosa to repeated, pulsatile exposure to specific bile components and examined changes in gene expression. Initial 2D experiments with a range of bile salts observed that taurochenodeoxycholate (TCDC) impacted upon NF-κB activation without causing cell death. Informed by this, the 3D oesophageal model was repeatedly exposed to TCDC in the presence and absence of acid, and the epithelial cells underwent gene expression profiling. We identified ~300 differentially expressed genes following each treatment, with a large and significant overlap between treatments. Enrichment analysis (Broad GSEA, DAVID and Metacore™; GeneGo Inc) identified multiple gene sets related to cell signalling, inflammation, proliferation, differentiation and cell adhesion. Specifically NF-κB activation, Wnt signalling, cell adhesion and targets for the transcription factors PTF1A and HNF4α were highlighted. Our data suggest that HNF4α isoform switching may be an early event in Barrett's pathogenesis. CDX1/2 targets were, however, not enriched, suggesting that although CDX1/2 activation reportedly plays a role in BM development, it may not be an initial event. Our findings highlight new areas for investigation in the earliest stages of BM pathogenesis of oesophageal diseases and new potential therapeutic targets., (© 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.)

Background: The relationship between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia is still not well understood. Towards obtaining a better understanding, concentrations of bile acids were measured., Patients and Methods: This study was carried out with the participation of 14 facilities in Japan, and 2283 samples were collected. The subjects with bile acid concentrations equal to or higher than the limit of detection were divided into four groups of equal size (group A: 0-25%, group B: 26-50%, group C: 51-75%, and group D: 76-100%). Thus, including the control group, there were five groups in total. The odds that the control group would develop atrophic gastritis and intestinal metaplasia was set as 1,and the odds ratios (OR) in groups A, B, C and D were calculated based on the odds in the control group., Results: Regarding the development of atrophic gastritis, no increased risk was observed in either the Helicobacter pylori (H. pylori)-positive or -negative cases. The OR for the development of intestinal metaplasia were significantly higher, for both cases with and without H. pylori infection, in group D., Conclusion: High concentrations of bile acid seem to be associated with an elevated risk of intestinal metaplasia., (© 2013 The Authors. Digestive Endoscopy © 2013 Japan Gastroenterological Endoscopy Society.)

In gastroesophageal reflux disease (GERD) symptoms arise due to reflux of gastric content into the oesophagus. However, the relation between magnitude and onset of reflux and symptom generation in GERD patients is far from simple; gastroesophageal reflux occurs several times a day in everyone and the majority of reflux episodes remains asymptomatic. This review aims to address the question how reflux causes symptoms, focussing on factors leading to enhanced reflux perception. We will highlight esophageal sensitivity variance between subtypes of GERD, which is influenced by peripheral sensitization of primary afferents, central sensitization of spinal dorsal horn neurons, impaired mucosal barrier function and genetic factors. We will also discuss the contribution of specific refluxate characteristics to reflux perception, including acidity, and the role of bile, pepsin and gas and proximal extent. Further understanding of reflux perception might improve GERD treatment, especially in current partial responders to therapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background/aims: To establish a rat model mimicking human bile reflux for studying the pathological effects of chronic bile reflux., Materials and Methods: The duodenum of Sprague-Dawley rats was transected below the opening of the common bile duct, and a gastrojejunostomy was performed at the greater curvature of the forestomach. After the rats demonstrated bile reflux for 1 year, we studied the pathological features of the glandular stomach and forestomach mucosa. We also studied the effect of bile reflux on gastrin expression in the glandular stomach mucosa by using immunohistochemistry., Results: Chronic bile reflux caused significant hyperplasia and expansion of gastric glands in the glandular stomach. Dysplasia and cancer formation also developed, but the incidence was significantly lower than that reported in the literature. Intestinal metaplasia and ulceration in the glandular stomach were also rare. In the forestomach, the squamous epithelium showed significant hyperplasia and keratinization along with keratin pearls and keratocysts. Intestinal metaplasia was rare and no tumorigenesis was observed. Chronic bile reflux significantly increased gastrin expression in the glandular stomach mucosa., Conclusions: When simulating the physiological bile reflux pathway, chronic bile reflux caused hyperplasia and expansion of gastric glands in the glandular stomach and squamous epithelial hyperplasia and keratinization in the forestomach.

The clinical scenario of a neurologically impaired child with a prolonged history of gastroesophageal reflux disease that underwent open Roux-en-Y gastrojejunostomy with subsequent development of severe symptomatic bile reflux is reported. The presentation, evaluation, and surgical management by laparoscopic revision to a modified esophagogastric dissociation are discussed., (Published by Elsevier Inc.)