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Endoscopic placement of biliary stent is a well-established palliative treatment for biliary obstruction. However, duodenobiliary reflux after stent placement has been a common problem which may lead to dreadful complications. This paper designed a novel anti-reflux biliary stent with a cone spiral valve. Fluid-Structure Interaction (FSI) simulations were established to evaluate the efficiency of the anti-reflux stent comparing with a clinically applied standard stent. According to the stress distribution of the valve, the fatigue performance in the stress concentration area was analyzed. The results show that when the antegrade flow through the valve, the cone spiral valve could stretch and open to realize adequate drainage under the normal physiological pressure of biliary tract; When the duodenal reflux through the valve, the valve would be compressed and close with a result of nearly zero at the outlet flow rate. Furthermore, the anti-reflux stent achieved improved radial mechanical performance with 2.7 times higher radial stiffness than standard stent. Finite element analysis (FEA) also indicates that compared with the standard stent, the addition of the anti-reflux valve had little negative effect on flexibility of the stent. Fatigue analysis results showed that the valve was reliable. This research provides the new stent with a cone spiral valve and proves that it is technically feasible and effective for preventing the duodenobiliary reflux while ensuring the antegrade bile flow without compromising the other biomechanical performances.

Gallstone disease is the most common risk factor for cholangitis. In an anatomically normal bile duct system, cholangitis does not occur without the presence of stones. Endoscopic retrograde cholangiography with papillotomy and stone extraction is a well-established curative therapy for gallstones in the common bile duct. More important, papillotomy prevents recurrent episodes. The present case report describes a 73-year-old male with recurring cholangitis in a clear bile duct system after previous papillotomy. An etiology of duodenal reflux into the common bile duct due to heavy lifting is proposed.

Hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion, Barrett’s Esophagus, a possible consequence of Gastro-Esophageal Reflux Disease. Obesity is known to mediate esophageal carcinogenesis through different mechanisms including insulin-resistance leading to hyperinsulinemia, which may mediate cancer progression via the insulin/insulin-like growth factor axis. We used the hyperinsulinemic non-obese FVB/N (Friend leukemia virus B strain) MKR (muscle (M)-IGF1R-lysine (K)-arginine (R) mouse model to evaluate the exclusive role of hyperinsulinemia in the pathogenesis of EAC related to duodeno-esophageal reflux. FVB/N wild-type (WT) and MKR mice underwent jejunum-esophageal anastomosis side—to end with the exclusion of the stomach. Thirty weeks after surgery, the esophagus was processed for histological, immunological and insulin/Insulin-like growth factor 1 (IGF1) signal transduction analyses. Most of the WT mice (63.1%) developed dysplasia, whereas most of the MKR mice (74.3%) developed squamous cell and adenosquamous carcinomas, both expressing Human Epidermal growth factor receptor 2 (HER2). Hyperinsulinemia significantly increased esophageal cancer incidence in the presence of duodenal-reflux. Insulin receptor (IR) and IGF1 receptor (IGF1R) were overexpressed in the hyperinsulinemic condition. IGF1R, through ERK1/2 mitogenic pattern activation, seems to be involved in cancer onset. Hyperinsulinemia-induced IGF1R and HER2 up-regulation could also increase the possibility of forming of IGF1R/HER2 heterodimers to support cell growth/proliferation/progression in esophageal carcinogenesis.

BackgroundInvestigations of molecular mechanisms behind the progression of neoplastic changes in the esophagus have uncovered the role of the COX & 5-Lox pathways. Human squamous esophageal mucosa produces relatively large amounts of eicosanoids in the presence of inflammation. Laboratory and epidemiological data suggest that aspirin and non-steroidal anti-inflammatory drugs may be chemo preventive through their inhibitory effect on COX25, 10. Cell culture studies have shown that the members of the mitogen activated protein (MAP) kinase family plays an important role in the development of bile acid-induced carcinogenesis. Differences in MAPK pathways activated by bile exposure were also noted in esophageal squamous cell lines and biopsies from patients with GERD. The protective role of aspirin and its molecular mechanism is not well understood.Aims1.The effect of duodenal reflux on esophageal mucosa.2.The role of aspirin in preventing duodenal reflux induced esophageal mucosa changes.3.If it is proven to be preventive, the mechanism of its action. A duodenal reflux rat animal model was used by an end- to-side esophago duodenostomy.MethodsTotal of 56 rats was included. 3 were "Naive control" animals which did not undergo the surgical procedure. The remaining animals were divided into two groups: Surgery alone (experimental) and Surgery + aspirin [therapy group], esophagoduodenostomy. At 40 weeks, the rats were euthanized and appropriate esophageal samples were analysed for histopathology and p38 & ERK MAP kinases, VEGF, protease activity and caspase 3 activities.ResultsThe presence of gross mucosal nodularity was seen in 21 and 10 rats of the experimental and therapy group respectively (p = 0.03; Table 1). Reflux-associated changes such as basal cell hyperplasia were more common in the experimental group, however this association did not reach statistical significance (p = 0.15; Table 1). Epithelial hyperplasia was seen more in the experimental group, which was prevented by aspirin [p

The pathogenesis of gastrointestinal reflux disease is multifactoral. Integral to the disease process is the refluxate itself. The characteristics and composition of the refluxate are dependent on several physiological variables. The refluxate may contain varying concentrations of acid, pepsin, gas, or contents of duodenal reflux (such as bile acid and pancreatic enzymes). Characteristics such as volume and proximal extent of the refluxate, and the chemical content of this refluxate can strongly influence the risk of symptom perception. Strong acid (pH4) and duodeno-gastro-oesophageal reflux are also implicated in the development of mucosal damage in the form of oesophagitis, Barrett's metaplasia and oesophageal adenocarcinoma. The manifestation of disease, however, is not entirely reliant on the refluxate, which must be considered in the context of the genetic, environmental and psychological susceptibility of the individual.

Summary Gastric contents were sampled in horses via nasogastric tube to determine changes in pH and bile salt concentrations during feeding and fasting periods. The horses were rotated through 4 feeding protocols. (1) hay; (2) hay with twice daily grain meals; (3) and (4) fasting preceded by either hay only or hay and grain. Sequential, hourly samples were collected from 3 horses prepared with gastric cannulas. Horses were fed hay twice daily and grain mix either twice daily or in small aliquots dispensed every 90 min. The horses were sampled during normal feeding or after 14 h of feed deprivation. Gastric pH values varied with time, but there was no significant difference between the feeding protocols or the fasting period on mean pH. Bile salt concentrations in fasted animals averaged 0.23–0.44 mmol/1 with individual samples greater than 0.9 mmol/1. The bile salt concentrations in fed animals were consistently below 0.2 mmol/1. The effect of bile salt and acid on the stratified squamous gastric mucosa was tested in vitro. Mucosa, stripped of muscle and serosal layers, was mounted in Ussing chambers and the electrical potential difference (PD) across the tissue recorded. Sodium taurocholate or deoxycholate (0.3 mmol/1, bile salt) and/or HCl were added to the mucosal bathing solutions. The bile salt alone had no significant effect. Addition of acid (pH 2.5) to control tissues caused a decrease in the PD, which recovered within 20 min. Addition of acid to tissues exposed to bile salts resulted in a significant decrease in the PD, which did not recover. We conclude that combinations of bile salts and acid are more injurious to the stratified squamous gastric mucosa of the equine than acid alone. Concentrations of bile salts and acid sufficient to alter the electrolyte transport function of this mucosa can be found in the gastric contents of horses deprived of feed for as little as 14 h.

Было проведено комплексное обследование 86 больных хроническим неатрофическим гастритом с дуоденогастральным рефлюксом, которое включало рН-метрию, эзофагогастродуоденоскопию, двойное тестирование на хеликобактерную инфекцию и гистологические исследования слизистой желудка по 4 - м топографическим зонам. Было выяснено, что частота выявления активных форм хеликобактерной инфекции была наибольшая - 100 % - на слизистой тела желудка по малой кривизне, а наименьшая - 28 % - на слизистой тела желудка по большой кривизне., Було проведено комплексне обстеження 86 хворих на хронічний не атрофічний гастрит при наявності дуоденогастрального рефлюксу, яке включало рН-метрію, езофагогастродуоденоскопію, подвійне тестування на гелікобактерну інфекцію і гістологічні дослідження слизової шлунка по 4-м топографічним зонам. Було з'ясовано, що частота виявлення активних форм гелікобактерної інфекції була найбільша – 100% - на слизовій тіла шлунку по малій кривині, а найменша – 28% - на слизовій тіла шлунку по великій кривині., It was a comprehensive survey of 86 patients with chronic non-atrophic gastritis with duodenal reflux which included pH meter, esophagogastroduodenoscopy, double testing of Helicobacter pylori infection and histological studies of the gastric mucosa to 4 - m topographic zones. It was found that the incidence of active forms of H. pylori infection was the largest - 100% - in the body of the stomach mucosa in the small curvature, and the lowest - 28% - on the mucosa of the stomach body on the greater curvature.

An excessive duodenal reflux induced by surgery has been widely accepted to cause gastric carcinogenesis in the remnant stomach. As one of causative factors for malignancy, N-nitroso compounds produced by enteric bacteria have been postulated. However, there is no concrete information to prove this hypothesis. This study was undertaken to elucidate the factors underlying the remnant stomach carcinogenesis, by giving thiazolidine-4-carboxylic acid (thioproline; TPRO) to the rats with duodenal reflux as a nitrite scavenger. Operated 39 animals were used, divided into 2 groups; one with a diet containing 0.5% TPRO (n=18), and the other with a diet without TPRO (n=21). Adenocarcinoma developed in 16 rats out of 21 (76.2%) of untreated rats, whereas adenocarcinoma was detected in 1 rat of the TPRO-treated rats (5.6%). TPRO thus prevented the development of gastric cancer in the remnant stomach, thereby suggesting a concern of nitroso compounds to the carcinogenesis.

OBJECTIVE: To assess the long-term results of the duodenal switch operation made for pathologic transpyloric duodenogastric reflux (DGR). SUMMARY BACKGROUND DATA: DGR symptoms and lesions are poorly responsive to medical treatment. METHODS: A duodenal switch operation was made on 48 patients suffering from pathologic transpyloric DGR either unrelated (n = 28) or secondary (n = 20) to previous upper gastrointestinal (GI) surgery, including cholecystectomy or vagotomy. The diagnosis was based on the combination of several objective arguments: a long history of gastric symptoms (ie, nausea, epigastric pain, and/or bilious vomiting) poorly responsive to medical treatment (48 of 48), gastroesophageal reflux symptoms unresponsive to proton-pump inhibitors (PPI) (23 of 29), gastritis on upper GI endoscopy (37 of 48) and/or at histology (28 of 41), presence of a bilious gastric lake at >1 upper GI endoscopy (30 of 48), DGR at diisopropyl iminodiacetic acid (DISIDA) scintigraphy scanning (7 of 13), pathologic 24-hour intragastric bile monitoring with the Bilitec device (40 of 41), and absence of Helicobacter pylori antral infection (39 of 41). RESULTS: At follow-up (median, 81 months), gastric symptoms were nil, had improved, and remained unchanged in 29 (60.4%), 16 (33.3%), and 2(4.2%) patients, respectively, and 1 patient experienced symptomatic recurrence after a 92-month symptom-free period (2.1%). Among the 44 patients who had postoperative upper GI endoscopy, 42 (95.5%) had no gastritis whereas 5 (11.3%) had an ulcer at the duodenojejunostomy. Gastric exposure to bile at postoperative 24-hour intragastric Bilitec test in 36 patients was nil, within the normal range, and still slightly pathologic in 15 (41.7%), 19 (52.8%), and 2 (5.5%), respectively. CONCLUSIONS: The duodenal switch operation made on patients in whom diagnosis of pathologic transpyloric DGR is supported by several objective arguments provides most of them with symptomatic and endoscopic improvement parallel to abolishment or normalization of gastric exposure to bile. Postoperative PPI therapy during a 2-month period is to be recommended to prevent the development of an anastomotic ulcer.

To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer.A total of 37 reflux juice samples (13 Billroth I, 24 Billroth II) were employed in the present study. A two-stage transformation assay using BALB/c 3T3 cells was carried out to test the initiating or promoting activity of these samples.Two of 18 (11.1%) reflux samples exerted initiating activities, whereas 9/19 (47.4%) samples enhanced the MNNG-initiating cell transformation, suggesting the duodenal reflux juice might more frequently possess the tumor-promoter activity (P = 0.029). In addition, there was no difference in initiating activities of the samples irrespective of surgical procedures (P = 0.488), while Billroth II samples exhibited stronger tumor-promoter activity than Billroth I samples (P = 0.027). Furthermore, the promoter activities were well correlated with the histological changes of the stomas (r(s) = 0.625, P = 0.004), but neither their cytotoxicities nor initiating activities had this correlation (Probabilities were 0.523 and 0.085, respectively).The duodenal reflux juice from patients with remote postgastrectomy did have carcinogenic potential, and suggested that tumor-promoting activity should principally account for the high incidence of gastric cancer in gastrectomy patients. In contrast, it is difficult to explain the high stump-cancer incidence with the N-nitroso compounds theory-a popular theory for the intact stomach carcinogenesis, and it seemed to be justified to focus chemo-prevention of this cancer on the tumor-promoting potential of reflux juice.

Background: The diagnosis of patients with short segments of intestinal metaplasia in the distal esophagus, has increased in recent years. Aim: To assess the clinical, pathological and functional features of patients with esophageal intestinal metaplasia. Patients and methods: A prospective study was performed in 95 control subjects, 115 patients with cardial intestinal metaplasia and 89 patients with short Barret esophagus with intestinal metaplasia. All had clinical and endoscopic assessments, esophageal manometry and determination of 24 h esophageal exposure to acid and duodenal content. Results: Control patients were younger and, in this group, the pathological findings in the mucosa distal to the squamous-columnar change, showed a preponderance of fundic over cardial mucosa. In patients with intestinal metaplasia and short Barret esophagus, there was only cardial mucosa, that is the place where intestinal metaplasia implants. Low grade dysplasia was only seen in the presence of intestinal metaplasia. Gastroesophageal sphincter pressure decreased and gastric and duodenal reflux increased along with increases in the extension of intestinal metaplasia. Conclusions: These findings confirm the need to obtain multiple biopsies from the squamous-columnar mucosal junction in all patients with gastroesophageal reflux symptoms, for the detection of early pathological changes of Barret esophagus and eventual dysplasia.

Warm Water Ampullary Washing: A Potential Needle-Knife Sphincterotomy Sparing Technique Emilio De la Morena, Elena Perez de Arellano, Yago Gonzalez-Lama, Esperanza Tomas-Moros Background: Needle-knife sphincterotomy (NKS) is an alternative endoscopic sphincterotomy (ES) technique used when selective biliary canulation (SBC) fails, but it is difficult to learn and is an independent risk factor for postERCP pancreatitis. Easier and safer canulation, NKS sparing, handlings are thus desirable. Objective: To report our preliminary results with a new canulation facilitating technique, the warm water ampullary washing (WAW). Method: WAW is performed when guide-wire assisted SBC fails and sphincter of Oddi spasm is one major presumptive cause of the failure. The ampoule is washed with 50 cc of tap water empirically titrated at 38-40 C using a canulotome inserted a few millimetres in the papillary orifice caring not to nail the tip to permit the duodenal reflux of the water and prevent pancreatic injection. After WAW a second SBC attempt is tried and if it fails again a NKS is performed. Results: Along one year 66 ES were indicated in 75 patients. Initially CSB and ES were performed in 54 (82%) and NKS in 5. WAW was tried in 7 and allowed CSB and ES in 4. Thus the final number of ES performed was 58 (88%) and the theoretic 12 (18%) NKS dropped to the real 8 (12%) (pZNS). The 4 WAW issues had healthy papillae (HP) (2 normal and 2 mild papillitis) whereas the 3 WAW failures had ill papillae (IP) (2 severe papillitis, 1 impacted stone). All 8 patients who required NKS had IP. Among the 3 WAW failures 1 mild pancreatitis was registered. Compared with 225 historical controls NKS dropped from 16% to 12% (pZNS). However NKS in IP patients rose from 7% to 12% (pZNS) and NKS in HP patients fell from 9% to 0 (pZ0.00002). Conclusion: With these results we hypothesise that WAW facilitates the SBC and allows ES in HP patients sparing NKS in them and limiting it to IP patients.

Insulin-stimulated gastric secretion alone, without reference to basal secretion, has been examined in 45 male patients with duodenal ulcer in whom no gastric operation had been performed and in 124 patients following vagotomy for duodenal ulcer. Gastric juice was examined in terms not only of conventional indices, observed volume, titratable acidity and acid output, but also Vg, the volume corrected for pyloric loss and duodenal reflux. The range of secretion of the unoperated subjects was established in terms of peak and half-totwo-hour values for all indices. By reference to these ranges, secretion of postvagotomy subjects could be divided into two groups: (a) those with secretion within the preperative range, and (b) those with secretion less than the lower limit of the preoperative range. The best discrimination was given by Vg; those within the preoperative range (peak Vg in excess of 140 ml/hour and Vg half to two hours in excess of 105 ml/hour) had a 50% liability to recurrent ulcer, while those below the preoperative range had a zero liability to recurrent ulcer. Of the conventional indices acid output gave the best discrimination, which was almost as good as Vg. Peak acid output of 8 mmol/hour or acid output one half to two hours of 525 mmol/hour discriminated into two groups, with a 50% or zero liability to recurrent ulcer. Titratable acidity (Hollander's index of secretion), being highly susceptible to reflux, was not an adequate discriminant.

Pyloric function after Ramstedt's pyloromyotomy was assessed in seven patients aged five to eleven years and compared to that in sixteen normal children. Gastric emptying (T 1/2) of liquid, as measured by the double sampling test, was faster in patients than in normal children. Duodenal reflux was calculated from the sodium content in gastric aspirates. At rest, it was greater in patients than in normal children. In the poststimulatory state, there was no difference. Gastric acid secretion was similar in both groups. Rapid gastric emptying might explain the high incidence of peptic ulcer reported in several series of long-term follow-up patients. Increased duodenal reflux at rest might account for a similar increased incidence in gastritis and dyspepsia.

Serum gastrin has been studied in dogs with and without surgically produced duodenal reflux. Fasting levels and the gastrin response to a standard meal have been assayed using a radioimmunoassay technique. Duodenal reflux caused no significant change in fasting serum gastrin immuno-reactivity but led to a markedly elevated and prolonged gastrin response to a standard meal.

A method, featuring perfusion of both gastric and duodenal markers with collections from the stomach and duodenum, was developed and validated for simultaneous measurements of total duodenal and gastric secretory outputs in man. Calculations of duodenal reflux into the stomach, of contamination of duodenal contents by gastric contents, and of the amounts -recycled between the two organs were made. The values so obtained were used to establish application of duodenal perfusion (with simultaneous gastric aspiration) for precise measurements of total secretions into the duodenum by simple calculations. The technique was used to show that total pancreatic enzyme output after intraduodenal stimulation by perfused amino acids was identical with that obtained after a maximally tolerated dose of pancreozymin given by vein. However, simultaneous intraduodenal and intravenous stimulation caused a pancreatic enzyme output significantly exceeding either method of stimulation alone, or any previously reported, thereby suggesting that conventional stimuli cannot attain maximal secretory capacity for enzymes. When applied to determination of total bilirubin output in the duodenum, the results approximated those reported by other methods.

Forty patients with signs and symptoms of gastro-oesophageal reflux were studied with cholescintigraphy, a noninvasive method, to detect duodenogastric reflux. 150 patients subjected to cholescintigraphy for various medical reasons served as controls. Ten per cent of the patients wit signs and symptoms of gastro-oesophageal reflux and 14% of the control patients had duodenogastric reflux. Of the four patients with gastro-oesophageal and duodenogastric reflux three had ulcers or strictures on oesophagoscopy, whereas one had normal endoscopic appearance. The differences in the frequency of duodenogastric reflux between these groups are not statistically significant.

Insulin stimulated gastric secretion was studied in 74 unoperated duodenal ulcer patients (DUs), (20 women and 54 men). Three indices of secretion were studied--observed volume, acid output, and volume of gastric juice corrected for pyloric loss and duodenal reflux (VG). These three measurements were expressed both as peak secretion and as secretion during the 1/2 to two hour period after insulin, and also both before and after standardisation for height, making 12 different indices in all. From the data a significant correlation between insulin-stimulated secretion and height in DUs was found. A method of standardising each patient's secretion for height is described. We confirm a significantly higher insulin-stimulated secretion in men than in women and show that this difference can be explained by their difference in height. For each of the 12 indices of secretion, the range of secretion for the unoperated subjects was obtained. The same indices were measured in 155 postvagotomy patients, including 33 patients with recurrent DUs, and compared with the ranges of secretion established in the unoperated patients. Responses above the lower 95% tolerance limit of the preoperative range were designated positive and those below negative. The Hollander status was determined. It was found that the least satisfactory criterion was Hollander's (7% false negative and 69% false positive). The best was 1/2-2 VG standardised for height (3% false negatives and 43% false positives). The improvement in predictably was significant at the 0-0005 level.

Duodenal reflux of biliary-pancreatic secretions (DGR) has been incriminated in a certain number of acute and chronic disorders of the stomach and esophagus [1].

Twenty-one stomachs resected for carcinoma were studied histologically using the ‘Swiss-roll’ technique. Chronic gastritis with epithelial hyperplasia was present in all. There were two types of distribution of the gastritis. In 17 instances it extended continuously from the pylorus proximally up to or beyond the carcinoma. This type of gastritis could be due to reflux of duodenal contents into the stomach. In 4 stomachs the gastritis occurred only in the vicinity of the tumour but did not extend from the pylorus and could therefore not be the result of duodenal reflux. It is postulated that there may be two kinds of carcinoma. One type is associated with the epithelial hyperplasia of chronic gastritis, possibly resulting from duodenal reflux into the stomach, The other is also associated with chronic gastritis but the distribution does not suggest duodenal reflux.

Most methods of measurements of gastric emptying rely on the serial estimation of intragastric volume and do not separately account for the volume of fluid which has been added to the meal by gastric secretion, duodenal reflux, or swallowed saliva. The volume emptied is therefore underestimated. A method of measuring gastric emptying using [125I]RIHSA and the Volemetron is presented. The volume of fluid added to the meal is taken into consideration in this method, giving a more accurate reflection of gastric emptying. Using this method in the dog, emptying was found to be linear rather than exponential.

Hourly measurements of bile acids, bacterial flora, and pH were made from gastric aspirates collected over 24 hours in subjects taking a controlled diet. Significantly higher concentrations of total bile acids were found following truncal vagotomy and antrectomy (TV+A), 2.73±1.16 SEM mmol/l, than after truncal vagotomy and pyloroplasty (TV+P), 0.88±0.56 mmol/l (p

Pfeffer loops were created in ten dogs. Duodenal pressure was increased until pancreatic reflux occurred or until the experiment was terminated. Pressures above 125 cm of water were required to produce reflux of duodenal contents. Histologic changes, manifest by papillary parenchymal hemorrhage, occurred in the pancreatic duct papilla, suggesting that structural damage to the papilla from prolonged pressure is necessary for the occurrence of duodenal reflux.