Revisional Bariatric Surgery After Roux-en-Y Gastric Bypass for Bile Reflux: a Single-Center Long-Term Cohort Study.

PURPOSE: Revisional bariatric surgery (RBS) after primary Roux-en-Y gastric bypass (RYGB) is indicated for the efficient management of specific complications such as bile reflux. Published literature on this topic remains scarce as we aim to evaluate the long-term outcomes (10 years) of RBS for bile reflux after RYGB. MATERIAL AND METHODS: We conducted a single-center retrospective study of patients who underwent primary RYGB complicated by bile reflux and had RBS between 2008 and 2023. Our cohort was divided into two groups based on the etiology of bile reflux. Long-term surgical outcomes and nutritional status were reported and compared between the groups. RESULTS: A total of 41 patients (100% primary RYGB; 90.2% female, 97.6% white) were included. 56.1% (n = 23) of patients underwent Roux limb lengthening and the remaining 43.9% (n = 18) had a gastrogastric fistula takedown, with no significant differences in terms of intraoperative complications, estimated blood loss (p = 0.616), length of hospital stay (p = 0.099), and postoperative complications between the two groups. Long-term resolution of obesity-related medical conditions was demonstrated for all the evaluated comorbidities. Lastly, there was no reported mortality, bile reflux recurrence, or micro- and macro-nutrient deficiencies over the total follow-up period of 10 years. CONCLUSION: In our cohort, RBS after a primary RYGB for bile reflux management demonstrated safe and efficient short- and long-term surgical outcomes without any reported bile reflux recurrence or mortality. Adequate supplementation and close patient follow-up remain essential to decrease the morbidity and mortality associated with RBS as further studies are required to support our findings.

Pathological and immunohistochemical analysis of gastric mucosa after one anastomosis gastric bypass surgery.

BACKGROUND: One anastomosis gastric bypass (OAGB) is now the third most common bariatric surgery worldwide. This procedure is garnering increasing attention, but its complication of bile reflux and the associated risk of gastric carcinogenesis remains controversial. OBJECTIVE: The study aims to assess the impact of bile reflux on the gastric mucosa by comparing pathological and immunohistochemical results of gastric mucosa before and 2 years after OAGB surgery. METHODS: This retrospective study analyzed gastric lesions observed in gastroscopy before and after OAGB surgery. Pathological examinations were conducted on mucosal samples from proximal, middle and distal part of stomach, with a particular focus on the expression of Ki-67, P53, and CDX2 in immunohistochemistry. Ki-67 indicates cellular proliferation, P53 is a tumor suppressor protein, and CDX2 is a marker for intestinal differentiation. RESULTS: A total of 16 patients completed the follow-up. Regarding gastritis, presurgery nonerosive gastritis was found in two cases (12.5%), and postsurgery in six cases (37.5%). Erosive gastritis increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery, totaling an increase from three to nine cases (p = .028). Bile reflux in the stomach increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery. Most lesions in the proximal, middle, and distal part of stomach were relatively mild, with normal tissue states being predominant. Mild inflammation was found in all three areas, whereas moderate inflammation, intestinal metaplasia, and glandular atrophy were less common. No cases of severe inflammation were noted. The expression of gastric biomarkers CDX-2, Ki67, and P53 showed no significant statistical variation in different areas. CONCLUSION: Bile reflux does occur after OAGB, but its incidence is not high. Based on the immunohistochemical and pathological results of the gastric mucosa 2 years post-OAGB, there seems to be no significant causal relationship between OAGB and oncogenic inflammation around the gastric tube.

USP50 regulates NLRP3 inflammasome activation in duodenogastric reflux-induced gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.

Cholecystokinin-Induced Duodenogastric Bile Reflux Increases the Severity of Indomethacin-Induced Gastric Antral Ulcers in Re-fed Mice.

BACKGROUND/AIMS: We examined the involvement of cholecystokinin (CCK) in the exacerbation of indomethacin (IND)-induced gastric antral ulcers by gastroparesis caused by atropine or dopamine in mice. METHODS: Male mice were fed for 2 h (re-feeding) following a 22-h fast. Indomethacin (IND; 10 mg/kg, s.c.) was administered after re-feeding; gastric lesions were examined 24 h after IND treatment. In another experiment, mice were fed for 2 h after a 22-h fast, after which the stomachs were removed 1.5 h after the end of the feeding period. Antral lesions, the amount of gastric contents, and the gastric luminal bile acids concentration were measured with or without the administration of the pro- and antimotility drugs CCK-octapeptide (CCK-8), atropine, dopamine, SR57227 (5-HT3 receptor agonist), apomorphine, lorglumide (CCK1 receptor antagonist), ondansetron, and haloperidol alone and in combination. RESULTS: IND produced severe lesions only in the gastric antrum in re-fed mice. CCK-8, atropine, dopamine, SR57227 and apomorphine administered just after re-feeding increased bile reflux and worsened IND-induced antral lesions. These effects were significantly prevented by pretreatment with lorglumide. Although atropine and dopamine also increased the amount of gastric content, lorglumide had no effect on the delayed gastric emptying provoked by atropine and dopamine. Both ondansetron and haloperidol significantly inhibited the increase of bile reflux and the exacerbation of antral lesions induced by atropine and dopamine, respectively, but did not affect the effects of CCK-8. CONCLUSIONS: These results suggest that CCK-CCK1 receptor signal increases bile reflux during gastroparesis induced by atropine and dopamine, exacerbating IND-induced antral ulcers.

Comparative efficacy of uncut Roux-en-Y and Billroth II anastomosis in gastrointestinal reconstruction following laparoscopic radical gastrectomy for distal gastric cancer.

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.

Age and incidence of occult pancreaticobiliary reflux in patients with benign gallbladder diseases.

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.

Uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Choosing an optimal reconstruction method is pivotal for patients with gastric cancer undergoing distal gastrectomy. The uncut Roux-en-Y reconstruction, a variant of the conventional Roux-en-Y approach (or variant of the Billroth II reconstruction), employs uncut devices to occlude the afferent loop of the jejunum. This modification is designed to mitigate postgastrectomy syndrome and enhance long-term functional outcomes. However, the comparative benefits and potential harms of this approach compared to other reconstruction techniques remain a topic of debate. OBJECTIVES: To assess the benefits and harms of uncut Roux-en-Y reconstruction after distal gastrectomy in patients with gastric cancer. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, WanFang Data, China National Knowledge Infrastructure, and clinical trial registries for published and unpublished trials up to November 2023. We also manually reviewed references from relevant systematic reviews identified by our search. We did not impose any language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing uncut Roux-en-Y reconstruction versus other reconstructions after distal gastrectomy for gastric cancer. The comparison groups encompassed other reconstructions such as Billroth I, Billroth II (with or without Braun anastomosis), and Roux-en-Y reconstruction. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The critical outcomes included health-related quality of life at least six months after surgery, major postoperative complications within 30 days after surgery according to the Clavien-Dindo Classification (grades III to V), anastomotic leakage within 30 days, changes in body weight (kg) at least six months after surgery, and incidence of bile reflux, remnant gastritis, and oesophagitis at least six months after surgery. We used the GRADE approach to evaluate the certainty of the evidence. MAIN RESULTS: We identified eight trials, including 1167 participants, which contributed data to our meta-analyses. These trials were exclusively conducted in East Asian countries, predominantly in China. The studies varied in the types of uncut devices used, ranging from 2- to 6-row linear staplers to suture lines. The follow-up periods for long-term outcomes spanned from 3 months to 42 months, with most studies focusing on a 6- to 12-month range. We rated the certainty of evidence from low to very low. Uncut Roux-en-Y reconstruction versus Billroth II reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to major postoperative complications (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.24 to 4.05; I² = 0%; risk difference (RD) 0.00, 95% CI -0.04 to 0.04; I² = 0%; 2 studies, 282 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.64, 95% CI 0.29 to 1.44; I² not applicable; RD -0.00, 95% CI -0.03 to 0.02; I² = 32%; 3 studies, 615 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, low- to very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Billroth II reconstruction may make little to no difference to changes in body weight (mean difference (MD) 0.04 kg, 95% CI -0.84 to 0.92 kg; I² = 0%; 2 studies, 233 participants; low-certainty evidence), may reduce the incidence of bile reflux into the remnant stomach (RR 0.67, 95% CI 0.55 to 0.83; RD -0.29, 95% CI -0.43 to -0.16; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 7; 1 study, 141 participants; low-certainty evidence), and may have little or no effect on the incidence of remnant gastritis (RR 0.27, 95% CI 0.01 to 5.06; I2 = 78%; RD -0.15, 95% CI -0.23 to -0.07; I2 = 0%; NNTB 7, 95% CI 5 to 15; 2 studies, 265 participants; very low-certainty evidence). No studies reported on quality of life or the incidence of oesophagitis. Uncut Roux-en-Y reconstruction versus Roux-en-Y reconstruction In the realm of surgical complications, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may make little to no difference to major postoperative complications (RR 4.74, 95% CI 0.23 to 97.08; I² not applicable; RD 0.01, 95% CI -0.02 to 0.04; I² = 0%; 2 studies, 256 participants; very low-certainty evidence) and incidence of anastomotic leakage (RR 0.34, 95% CI 0.05 to 2.08; I² = 0%; RD -0.02, 95% CI -0.06 to 0.02; I² = 0%; 2 studies, 213 participants; very low-certainty evidence). We are very uncertain about these results. Focusing on long-term outcomes, very low-certainty evidence suggests that uncut Roux-en-Y reconstruction compared with Roux-en-Y reconstruction may increase the incidence of bile reflux into the remnant stomach (RR 10.74, 95% CI 3.52 to 32.76; RD 0.57, 95% CI 0.43 to 0.71; NNT for an additional harmful outcome (NNTH) 2, 95% CI 2 to 3; 1 study, 108 participants; very low-certainty evidence) and may make little to no difference to the incidence of remnant gastritis (RR 1.18, 95% CI 0.69 to 2.01; I² = 60%; RD 0.03, 95% CI -0.03 to 0.08; I² = 0%; 3 studies, 361 participants; very low-certainty evidence) and incidence of oesophagitis (RR 0.82, 95% CI 0.53 to 1.26; I² = 0%; RD -0.02, 95% CI -0.07 to 0.03; I² = 0%; 3 studies, 361 participants; very low-certainty evidence). We are very uncertain about these results. Data were insufficient to assess the impact on quality of life and changes in body weight. AUTHORS' CONCLUSIONS: Given the predominance of low- to very low-certainty evidence, this Cochrane review faces challenges in providing definitive clinical guidance. We found the majority of critical outcomes may be comparable between the uncut Roux-en-Y reconstruction and other methods, but we are very uncertain about most of these results. Nevertheless, it indicates that uncut Roux-en-Y reconstruction may reduce the incidence of bile reflux compared to Billroth-II reconstruction, albeit with low certainty. In contrast, compared to Roux-en-Y reconstruction, uncut Roux-en-Y may increase bile reflux incidence, based on very low-certainty evidence. To strengthen the evidence base, further rigorous and long-term trials are needed. Additionally, these studies should explore variations in surgical procedures, particularly regarding uncut devices and methods to prevent recanalisation. Future research may potentially alter the conclusions of this review.

Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome.

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

Outcomes of One-Anastomosis Gastric Bypass Conversion to Roux-en-Y Gastric Bypass for Severe Obesity: A Systematic Review and Meta-analysis.

One-anastomosis gastric bypass (OAGB) is an effective procedure to treat severe obesity. However, conversion to Roux-en-Y gastric bypass (RYGB) is increasing. We therefore conducted a systematic review to determine the safety and efficacy associated with OAGB-RYGB conversion. A systematic search was conducted by three independent reviewers using Medline, Embase, and the Cochrane library following PRISMA guidelines. Six studies including 134 patients were selected who were undergoing OAGB-RYGB conversion. The most common indications were reflux (47.8%), malnutrition (31.3%), and inadequate weight loss (8.2%). Study outcomes demonstrated 100% resolution of bile reflux. Overall, there was medium-term weight gain of 0.61 BMI. OAGB to RYGB conversion leads to resolution of reflux symptoms. However, it is associated with weight regain, albeit this may be acceptable to patients to treat biliary reflux.

In silico modelling of the effect of pyloric intervention procedures on gastric flow and emptying in a stomach with gastroparesis.

Pyloric interventions are surgical procedures employed to increase the gastric emptying rate in gastroparesis patients. In this study, we use an in silico model to investigate the consequences of pyloric intervention on gastric flow and emptying for two phenotypes of gastroparesis: antral hypomotility and decreased gastric tone. The transpyloric pressure gradient predicted by the in silico model, based on viscous fluid flow equations, is compared against in vivo measurements. Both phenotypes exhibit a similar pre-procedural emptying rate reduction, but after pyloric surgery, antral hypomotility case with preserved gastric tone shows significant improvements in emptying rates, up to 131%, accompanied by bile reflux from the duodenum into the stomach. Conversely, severely reduced gastric tone cases exhibited a post-procedural reduction in the net emptying rate due to the relatively larger bile reflux. In cases with a combination of antral hypomotility and reduced gastric tone, post-procedural improvements were observed only when both conditions were mild. Our findings highlight the pivotal role of the relative increase in pyloric orifice diameter in determining post-operative emptying rates. The study suggests a possible explanation for the selective response of patients toward these procedures and underscores the potential of in silico modelling to generate valuable insights to inform gastric surgery.

Reappraisal of optimal reconstruction after distal gastrectomy - a study based on the KLASS-07 database.

BACKGROUNDS: This study aimed to compare the incidence of bile reflux, quality of life (QoL), and nutritional status among Billroth II (BII), Billroth II with Braun anastomosis (BII-B), and Roux-en-Y (RY) reconstruction after laparoscopic distal gastrectomy (LDG). MATERIALS AND METHODS: We reviewed the prospective data of 397 patients from a multicentre database who underwent LDG for gastric cancer between 2018 and 2020 at 20 tertiary teaching hospitals in Korea. Postoperative endoscopic findings, QoL surveys using the European Organization for Research and Treatment of Cancer questionnaire (C30 and STO22), and nutritional and surgical outcomes were compared among groups. RESULTS: In endoscopic findings, bile reflux was the lowest in the RY group ( n =67), followed by the BII-B ( n =183) and BII groups ( n =147) at 1 year (3.0 vs. 67.8 vs. 84.4%, all P <0.05). The anti-reflux capability of BII-B was statistically better than that of BII, but not as perfect as that of RY. From the perspective of QoL, BII-B was not inferior to RY, but better than BII reconstruction in causing fewer STO22 reflux symptoms at 6 and 12 months. However, only RY caused fewer C30 nausea symptoms than BII at 6 and 12 months, but not BII-B. Nutritional status and morbidities were similar among the three groups, and the operative time did not differ between the BII-B and RY groups. CONCLUSIONS: BII-B cannot substitute for RY in preventing bile reflux, shortening the operative time, or reducing morbidities. Regarding short-term QoL, BII-B was sufficient to reduce STO22 reflux symptoms but failed to reduce C30 nausea symptoms postoperatively.

Association between endoscopic evidence of bile reflux and Barrett's esophagus: A large-scale case-control study.

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.

Comparison of three different anastomotic methods of sleeve gastrectomy with transit bipartition using an obese rodent model.

The long-term effects and safety of single-anastomosis sleeve ileal (SASI) bypass have not been confirmed. The one anastomosis procedure carries the risk of bile reflux, and Braun anastomosis has the capacity to reduce bile reflux. This study was designed to compare the influences of bile reflux and histological changes in the esogastric sections of rats. Obese Sprague-Dawley rats underwent sleeve gastrectomy with transit bipartition (RYTB) (n = 12), SASI (n = 12), SASI bypass with Braun anastomosis (BTB) (n = 12), esojejunostomy (EJ) (n = 12), and SHAM (n = 8) surgery. During the 12-week follow-up period, weight changes, glucose improvement, and changes in serum nutrition were evaluated. Histological expression and bile acid concentration in the rats in all groups were also evaluated. No significant differences in weight loss and glucose improvements were observed in the RYTB, SASI, and BTB groups. The RYTB and BTB groups had significantly lower bile acid concentration and albumin levels than the SASI group. In addition, mucosal height in the RYTB and BTB groups was significantly lower than in the SASI group. Braun anastomosis had a significant effect on anti-reflux. BTB may be a superior primary procedure due to its potential for parallel bariatric and metabolic improvements, effective anti-reflux effects, simplified operations, and avoidance of severe malnutrition. Further clinical studies are needed to confirm these findings.

Incomplete Intestinal Metaplasia of the Stomach Is more Related to Bile Reflux than Chronic Gastritis.

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/m2 for patients with IIM compared to 28 kg/m2 for those with CIM and 31.2 kg/m2 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.

Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q exactive focus mass spectrometry, network pharmacology, and molecular docking.

OBJECTIVE: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG). METHODS: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]. RESULTS: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways. CONCLUSIONS: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.

Short- and long-term outcomes of Roux-en-Y and Billroth II with Braun reconstruction in total laparoscopic distal gastrectomy: a retrospective analysis.

BACKGROUND: The controversy surrounding Roux-en-Y (R-Y) and Billroth II with Braun (BII + B) reconstruction as an anti-bile reflux procedure after distal gastrectomy has persisted. Recent studies have demonstrated their efficacy, but the long-term outcomes and postoperative quality of life (QoL) among patients have yet to be evaluated. Therefore, we compared the short-term and long-term outcomes of the two procedures as well as QoL. METHODS: The clinical data of 151 patients who underwent total laparoscopic distal gastrectomy (TLDG) at the Gastrointestinal Surgery Department of the Second Hospital of Fujian Medical University from January 2016 to December 2019 were retrospectively analyzed. Of these, 57 cases with Roux-en-Y procedure (R-Y group) and 94 cases with Billroth II with Braun procedure were included (BII + B group). Operative and postoperative conditions, early and late complications, endoscopic outcomes at year 1 and year 3 after surgery, nutritional indicators, and quality of life scores at year 3 postoperatively were compared between the two groups. RESULTS: The R-Y group recorded a significantly longer operative time (194.65 ± 21.52 vs. 183.88 ± 18.02 min) and anastomotic time (36.96 ± 2.43 vs. 27.97 ± 3.74 min) compared to the BII + B group (p < 0.05). However, no other significant differences were observed in terms of perioperative variables, including blood loss (p > 0.05). Both groups showed comparable rates of early and late complications. Endoscopic findings indicated similar food residuals at years 1 and 3 post-surgery for both groups. The R-Y group had a lower occurrence of residual gastritis and bile reflux at year 1 and year 3 after surgery, with a statistically significant difference (p < 0.001). Reflux esophagitis was not significantly different between the R-Y and BII + B groups in year 1 after surgery (p = 0.820), but the R-Y group had a lower incidence than the BII + B group in year 3 after surgery (p = 0.023). Nutritional outcomes at 3 years after surgery did not differ significantly between the two groups (p > 0.05). Quality of life scores measured by the QLQ-C30 scale were not significantly different between the two groups. However, on the QLQ-STO22 scale, the reflux score was significantly lower in the R-Y group than in the BII + B group (0 [0, 0] vs. 5.56 [0, 11.11]) (p = 0.003). The rest of the scores were not significantly different (p > 0.05). CONCLUSION: Both R-Y and B II + B reconstructions are equally safe and efficient for TLDG. Nevertheless, the R-Y reconstruction reduces the incidence of residual gastritis, bile reflux, and reflux esophagitis, as well as postoperative reflux symptoms, and provides a better quality of life for patients. R-Y reconstruction is superior to BII + B reconstruction for TLDG.

Bile reflux after bariatric surgery.

The growing epidemic of obesity and the increase in weight loss surgery has led to a resurgence of interest in biliary reflux because anatomical alterations may be refluxogenic. HIDA scan is the least invasive scan with good patient tolerability, sensitivity and reproducibility for the diagnosis of biliary reflux. Patients with more advanced oesophageal lesions have a higher degree of duodenal reflux. It has been shown in animal models and in vitro that there is more Barrett's and dysplasia with duodenal reflux. There are two cases of post-OAGB malignancy reported in 20 years, both without correlation with a biliary aetiology, so the carcinogenic risk probably remains theoretical. Prospective trials on OAGB should include endoscopy preoperatively and at 5-year intervals, to have data on the real effects of bile exposure on the gastric reservoir and oesophagus.