[Expert consensus on endoscopic diagnosis and treatment of the benign pancreaticobiliary junction disease (2023 edition)].

The pancreaticobiliary junction (PBJ) stands as a pivotal "hub" where the bile and pancreatic ductsmerge, directing the flow rate and direction of bile and pancreatic juice. Benign pancreaticobiliary junction diseases(BPBJD) can lead to compromised outflow of bile and pancreatic secretions, resulting in elevated pressures within the bile and pancreatic ducts, causing ductal dilation, secretion stasis, and stone formation.Furthermore, BPBJD can shift the direction of bile and pancreatic juice, inducing pancreaticobiliary reflux, bile-pancreatic reflux, or enterobiliary reflux, thereby causing both acute and chronic inflammation and tumors in the biliopancreatic system. Owing to the unique anatomical position of the PBJ and the often intricate and elusive symptoms of benign diseases in this region, clinicians might mainly address standard biliary and pancreatic diseases, overlooking the primary issues associated with the PBJ.Such oversight can yield less-than-optimal clinical outcomes. In response to this, the Gallbladder-Preserving Surgery Committee, Endoscopy Specialist Branch of Chinese Medical Doctor Association and the editorial board of the National Medical Journal of China assembled renowned domestic experts from the fields of hepatobiliary and pancreatic surgery and digestive endoscopy. Drawing upon the latest domestic and international research findings, as well as the clinical expertise of specialists from related fields within China, they have collaboratively developed an expert consensus on the endoscopic diagnosis and treatment of BPBJD. The overarching aim is to propagate and standardize the diagnosis and treatment approaches for BPBJD.

Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. METHODS: All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux. KEY RESULTS: We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = -0.714; P < .001) and PSPW index (R = -0.722; P < .001). CONCLUSIONS AND INFERENCES: Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance.

Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass.

INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.

Gastrogastric Fistula: an Unusual Cause for Severe Bile Reflux Following Conversion of Sleeve Gastrectomy to One Anastomosis Gastric Bypass.

INTRODUCTION: One anastomosis gastric bypass/mini-gastric bypass (OAGB/MGB) was first described in 2001 as a safe and effective procedure. It has been gaining popularity worldwide. Multiple authors have reported the need to re-operate on patients for bile reflux. We report a patient with severe bile reflux after laparoscopic conversion of sleeve gastrectomy (LSG) to OAGB/MGB. METHODS: A 33-year-old patient underwent a LSG in 2014. Postoperatively, she developed severe gastroesophageal acid reflux. In 2016, she underwent conversion of LSG to OAGB/MGB at the original institution for the treatment of her reflux symptoms. In 2017, she presented to us with epigastric pain, worsening reflux symptoms, steatorrhea, hypoproteinemia (6 g/dl), and body mass index of 25 kg/m2. Preoperative endoscopy revealed bile reflux, suture bezoar, and ulceration at the anastomosis. TECHNIQUE: Laparoscopic exploration started by identifying the anatomy and measuring the lengths of the biliopancreatic limb (350 cm) and the common channel (450 cm). Upon dissecting the pouch, a gastrogastric fistula extending from the antrum to the pouch was encountered. This was confirmed with intraoperative endoscopy with bile refluxing to the pouch. The fistula, antrum, and part of the pouch were resected. The patient was converted to Roux-en-Y gastric bypass. She had an uneventful postoperative recovery. At 3 months of follow-up, her weight was stable and her steatorrhea resolved. CONCLUSION: Patients with bile reflux after OAGB/MGB need a high index of suspicion to detect unusual causes. Gastrogastric fistula is an unusual etiology of bile reflux that was never reported in the literature previously.

Detecting Bile Reflux-the Enigma of Bariatric Surgery.

Duodeno-gastro-esophageal reflux, or bile reflux, is a condition for which there is no diagnostic gold standard, and it remains controversial in terms of carcinoma risk. This is pertinent in the context of an increasingly overweight population who are undergoing weight-loss operations that theoretically further increase the risk of bile reflux. This article reviews investigations for bile reflux based on efficacy, patient tolerability, cost, and infrastructure requirements. At this time, whilst no gold standard exists, hepatobiliary scintigraphy is the least invasive investigation with good-patient tolerability, sensitivity, and reproducibility to be considered first-line for diagnosis of bile reflux. This review will guide clinicians investigating bile reflux.

Bile Reflux Scintigraphy After Mini-Gastric Bypass.

BACKGROUND: Significant weight-loss and diabetes remission have been reported after mini-gastric bypass (MGB). Concern has been raised regarding postoperative bile reflux (BR), but it has not been demonstrated in previous studies. We set out to find out if BR is evident in hepatobiliary scintigraphy after MGB. METHODS: Nine consecutive patients, seven with type 2 diabetes, underwent MGB (15 cm gastric tube, 250-275 cm biliary limb) at our institution with a 12-month follow-up, with none lost to follow-up. Then, 10.7 months (8.6-13.0) after MGB, all patients underwent hepatobiliary scintigraphy and a reflux symptom questionnaire (GerdQ) was filled out. A gastroscopy with biopsies was done for all patients with a bile-reflux-positive scintigraphy. RESULTS: Mean age at operation was 56 years (41-65) and preoperative BMI 43.1 kg/m2 (34.2-54.6). Mean %EWL was 83.9 (49.5-128.3) at 12 months. Four patients reached diabetes remission and two became insulin-independent. Hepatobiliary scintigraphy showed a transient BR into the gastric tube for five patients. Bile tracer was found in the gastric tube at 23-58 min after the tracer injection and highest activity was 8% (1-8%) at 58 min. Bile tracer was not found in the esophagus of any of the patients. One patient with a positive scintigraphy in the gastric tube required re-operation. Two patients with reflux symptoms had a negative scintigraphy. CONCLUSION: Our results indicate that transient bile reflux is common after MGB in the gastric tube, but not in the esophagus. The clinical relevance of bile reflux needs further studies.

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma.

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.

The management of bilious vomiting in the neonate.

Bilious vomiting is synonymous with intestinal obstruction, be it functional or anatomical. In the neonate it may be due to congenital malformations of the gastrointestinal tract or develop due to acquired conditions, particularly intestinal complications associated with prematurity. This review considers the congenital malformations that may present with bilious vomiting and explores the diagnostic dilemmas faced in the preterm infant. The difficult issue of the need to exclude malrotation in term infants with bilious vomiting and the consequences of time-critical transfer is discussed.

Rate of duodenal-biliary reflux increases in patients with recurrent common bile duct stones: evidence from barium meal examination.

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.)

Congenital left intrahepatic bile duct draining into gastric wall mimicking biliary reflux gastritis.

Abnormalities and variations of the biliary ducts are not rare. Most aberrant bile ducts eventually drain into the descending part of duodenum through the papilla of vater. However, drainage of the left hepatic bile duct into the stomach is extremely rare. A 29-year old man was admitted to the hospital with the diagnosis of biliary reflux gastritis. Comprehensive imaging modalities were performed including electronic endoscopy, endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography and magnetic resonance cholangio-pancreatography. Finally, congenital ectopic left intrahepatic bile duct draining into the stomach was found, which caused biliary reflux gastritis. The patient did not receive any surgery. Good recovery was achieved by medical treatment.

Novel antireflux covered metal stent for recurrent occlusion of biliary metal stents: a pilot study.

BACKGROUND: Feasibility of antireflux metal stent (ARMS), designed to prevent duodenobiliary reflux, was reported in patients with distal malignant biliary obstruction. In this prospective pilot study, we aimed to evaluate a newly designed ARMS as a reintervention for self-expandable metallic stent (SEMS) occlusion believed to be caused by duodenobiliary reflux. PATIENTS AND METHODS: Patients with non-resectable distal malignant biliary obstruction were included in whom a prior SEMS was occluded as a result of sludge or food impaction between March 2010 and January 2012 at two Japanese tertiary referral centers. The occluded SEMS were endoscopically removed, if possible, and subsequently replaced by a newly designed ARMS. We evaluated the technical success rate and complications of ARMS and compared the time to occlusion of ARMS with that of prior SEMS. RESULTS: A total of 13 patients were included. ARMS was successfully placed in all patients in a single procedure. No procedure-related complications were identified. ARMS occlusion occurred in two patients (15%), the causes of which were sludge in one patient and unknown in the other. ARMS migration occurred in four patients (31%). ARMS patency time was significantly longer than that of prior SEMS (median, not available vs 58 days; P = 0.039). CONCLUSIONS: This newly designed ARMS is a technically feasible, safe, and effective reintervention for SEMS occlusion as a result of sludge or food impaction. An anti-migration mechanism to improve the outcomes of ARMS should be considered.

Optimal duration of medical treatment in superior mesenteric artery syndrome in children.

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.

Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases.

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.

Bridging across the ampulla with metal stents: evidences for intestinal bile reflux.

BACKGROUND/AIMS: To investigate the early intestinal bile reflux following the implantation of metal stent across the ampulla and the mechanism of reflux cholangitis. METHODOLOGY: Twenty-three patients with implantation of metal stent across the ampulla were recruited. Prior to the implantation, the white blood cell count, neutrophil percentage, total blood bilirubin, direct bilirubin and the trypsin content in the bile were recorded; 2-5 days after implantation these indices were measured again, as well as the 99mTc -DTPA radioactivity. RESULTS: A high percentage (82.61%) of patients showed 99mTc in the bile in 2 hours, which accounts for 1.73% of total intake. In 4 cases the radioactivity was not found. Bile lipase and amylase levels were significantly higher than that in prior to the stent implantation. There were no changes in the white blood cell count and neutrophil percentage after stent implantation. Additionally, the total blood bilirubin and direct bilirubin decreased. CONCLUSIONS: After the implantation of metal stent across the ampulla, there is evidence for the early intestinal bile reflux, without signs for the reflux cholangitis.

Optimal Duration of Medical Treatment in Superior Mesenteric Artery Syndrome in Children

The aim of this study was to investigate the outcome, and optimal duration of medical treatment in children with superior mesenteric artery syndrome (SMAS). Eighteen children with SMAS were retrospectively studied. The data reviewed included demographics, presenting symptoms, co-morbid conditions, clinical courses, nutritional status, treatments, and outcomes. The three most common symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early satiety (50%). The median duration of symptoms before diagnosis was 68 days. The most common co-morbid condition was weight loss (50%), followed by growth spurt (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in 72.2% of the patients. Medical management was successful in 13 patients (72.2%). The median duration of treatment was 45 days. Nine patients (50%) had good outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4 patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of medical management tended to be associated with worse outcomes (P=0.018). SMAS often developed in patients with normal BMI or no weight loss. Medical treatment has a high success rate, and children with SMAS should be treated medically for at least 6 weeks before surgical treatment is considered.

Prospective evaluation of duodenogastroesophageal reflux in gastroesophageal reflux disease patients refractory to proton pump inhibitor therapy.

BACKGROUND: Duodenogastroesophageal reflux (DGER) is considered an independent risk factor for complicated reflux disease (gastroesophageal reflux disease; GERD). However, the role of DGER in GERD patients refractory to proton pump inhibitors (PPI) remains poorly understood. METHODS: 85 patients with clinical reflux symptoms and a history of ineffective response to PPIs were enrolled in the study. Patients with elevated reflux measurement (pH and/or Bilitec measurement; n = 47) received pantoprazole 80 mg for 8 weeks. Clinical outcome was defined as response (≤2 symptoms/week) or nonresponse (≥3 symptoms/week). RESULTS: Of the 47 patients with elevated reflux measurement, 30 were classified as responders and 17 as nonresponders. Treatment with pantoprazole resulted in a significant reduction of acidic reflux in both PPI responders and PPI nonresponders. In contrast, DGER was only significantly reduced in the PPI responder group (22.8 ± 22.8 vs. 6.6 ± 10.8%; p < 0.05) but not in the PPI nonresponder group (24.5 ± 18.6 vs. 22.2 ± 12.7%; p > 0.05). CONCLUSIONS: The presented study firstly describes that nonresponsiveness to PPI is associated with a limited effect of PPIs on reducing DGER. Thus, persistent DGER may play a key role in mediating reflux symptoms refractory to high-dose PPIs.

[Clinical characteristics of patients with reflux esophagitis exhibiting gallbladder heat attacking the stomach or stagnant heat of the liver and stomach syndrome].

OBJECTIVE: To compare the characteristics of the traditional Chinese medicine (TCM) syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with reflux esophagitis (RE), in terms of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and helicobacter pylori (HP) infection. METHODS: Patients with RE were enrolled from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from June 2007 to December 2009 and patients exhibiting the syndrome of gallbladder heat attacking the stomach or stagnant heat of the liver and stomach were collected. The patients were requested to complete clinical questionnaires. The general data, characteristics of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and HP infection of the two patterns were compared. RESULTS: The average age of the selected patients with gallbladder heat attacking the stomach was older than that of the patients with stagnant heat of the liver and stomach (P<0.01) and the accompanying clinical signs and symptoms were more severe (P<0.01). The incidence of gallbladder diseases in patients with gallbladder heat attacking the stomach was higher than that of the patients with stagnant heat of the liver and stomach (P<0.01). The extent of the esophageal mucosal inflammation under endoscopy as well as the gastric bile reflux and the incidence of HP infection was also more severe (P<0.01). CONCLUSION: There are significant differences in several regards between the syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with RE. These characteristics may provide sound evidence for differentiation of signs and symptoms for this disease.

Pancreaticobiliary reflux in patients with a normal pancreaticobiliary junction: Pathologic implications.

Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and its pathologic implications has experienced tremendous progress during the last few years. This editorial reviews the current knowledge on this condition and its pathological implications on gallbladder diseases. The following aspects were defined appropriate for discussion: (1) Evidence of carcinogenesis associated with pancreaticobiliary reflux; (2) Evidence of pancreaticobiliary reflux in normal pancreaticobiliary junction; and (3) Evidence of sphincter of Oddi (SO) dysfunction as a cause of pancreaticobiliary reflux in normal pancreaticobiliary junction. The articles reviewed were selected and classified according to five levels of evidence: Level I, meta-analysis double-blind randomized clinical trials, Level II, cohort non-blinded studies and non-randomized clinical trials, Level III, good quality case-control studies and non-randomized cohort studies, Level IV, case series and poor quality case-control studies, and Level V, case report articles and experts' opinion. Evidence levels II, III, IV and V were found to support biliary carcinogenesis associated with pancreaticobiliary reflux in normal and abnormal pancreaticobiliary junction. The same levels of evidence were found to support the common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary junction, and SO dysfunction as the most plausible cause of this condition. Although an important body of research has been published regarding pancreaticobiliary reflux in normal pancreaticobiliary junction and its clinical significance, the current evidence does not fully support what has been suggested. Studies with evidence level I have not been undertaken. This is a fascinating subject of study, and if finally supported by evidence level I, the importance of this condition will constitute a major breakthrough in biliary pathology.