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Enterogastric reflux (EGR) is the reflux of bile and digestive enzymes from the small bowel into the stomach. While it is a normal physiologic process in small amounts, excessive reflux and chronic EGR can cause upper GI symptoms often mimicking more common diseases such as gallbladder disease and GERD that often leads to its underdiagnosis. Identifying EGR is significant as it has been associated with the development of gastroesophogeal pathology including gastritis, esophagitis, ulcers, and mucosal metaplasia. This article presents a 22-year-old male with enterogastric reflux causing upper abdominal pain and will discuss the role of hepatobiliary scintigraphy in its diagnosis.

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. 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. Mean age at operation was 56 years (41-65) and preoperative BMI 43.1 kg/m(2) (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. 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.

Background: Enterogastric reflux of bile is a major cause of morbidity following distal gastrectomy. Various reconstructive methods were developed to overcome this. Methods: A prospective randomised study included all patients undergoing distal gastrectomy for gastric cancer was conducted during the period June 2012 and November 2016. After resection, they were randomized to undergo Billroth II with Braun anastomosis (BEE) (n = 28) or Roux-en-Y (RY) gastrojejunostomy (n = 26). Endoscopy and biliary scintigraphy were done at 3 months to assess the severity of gastritis and the presence of bile reflux in remnant stomach. Stomach was biopsied for histopathology. Quality of life (QOL) was assessed using gastric cancer-specific questionnaire. Results: Demographics and nutritional status was similar. Intraoperative variables, post-operative recovery and hospital stay were not statistically different. Remnant stomach in BEE group showed more severe and extensive gastritis than RY group. The incidence of bile reflux on endoscopy was statistically significantly high in BEE (P < 0.0001). The histological findings of endoscopic biopsies were similar. The incidence of bile reflux on scintigraphy was lower in RY group (10.7% vs. 46.2%; P = 0.03). The QOL symptom score was similar. Conclusions: The incidence of bile reflux and severity of gastritis is less in patients who underwent RY gastrojejunostomy when compared to Billroth II with Braun anastomosis without any significant difference in QOL.

Background: The aim of this study was to present the long-term results of the cut-closed-reconnected (CCR)-Roux procedure for reflux gastritis. Methods: A retrospective analysis was performed on 14 patients with proven reflux gastritis and/or esophagitis who were treated at our institution with a CCR-Roux procedure between 1992 and 1997. Results: The closure of the afferent loop in the CCR-Roux procedure is effective and permanent. The CCR-Roux patients did not need a rest gastrectomy. No signs of Roux stasis syndrome were seen. There was a consistent weight gain at 2 and 5 years of follow-up. These results permit a comparison with those of the Roux-Y procedure and other alternative procedures as well. Conclusion: In the long run, the CCR-Roux procedure is effective in the treatment of reflux gastritis.

PURPOSE: To evaluate chemoprevention by celecoxib in cases of reflux-induced gastric adenocarcinoma, in Wistar rats that underwent gastrojejunostomy. METHODS: Sixty male Wistar rats of average age three months underwent surgery and were distributed into three groups: group 1, exploratory laparotomy; group 2, gastrojejunostomy; and group 3, gastrojejunostomy and daily celecoxib administration. After 53 weeks, the animals were sacrificed. Changes in the mucosa of the gastric body of group 1 and in the gastrojejunal anastomosis of groups 2 and 3, observed in histopathological and immunohistochemical examinations, were compared. All statistical analyses were performed using Epi-Info®, version 3.4.3. RESULTS: Comparison between groups 2 and 3 relative to the presence of adenocarcinoma showed a statistically significant difference (p=0.0023). Analysis of the association between groups 2 and 3 relative to COX-2 expression also showed a statistically significant difference (p=0.0018). CONCLUSION: Celecoxib had an inhibiting effect on gastric carcinogenesis induced by enterogastric reflux in an animal model. OBJETIVO: Avaliar a quimioprevenção pelo celecoxibe no adenocarcinoma gástrico induzido por refluxo, em ratos Wistar, submetidos a gastrojejunostomia. MÉTODOS: Sessenta ratos machos Wistar, com média de idade de três meses foram operados e distribuídos em 03 grupos: Grupo 1 - Os animais foram submetidos a laparotomia exploradora. Grupo 2 - Os animais foram submetidos a gastrojejunostomia. Grupo 3 - Os animais foram submetidos a gastrojejunostomia e tomaram celecoxib, diariamente. Após um período de 53 semanas, os animais foram sacrificados. As alterações da mucosa do corpo gástrico dos animais do grupo 1 e da anastomose gastrojejunal dos animais dos grupos 2 e 3 foram analisadas no exame histopatológico e imuno-histoquímica e foram comparadas. Todas as análises estatísticas foram realizadas pelo programa Epi Info®, versão 3.4.3. RESULTADOS: No cotejo entre os animais dos grupos 2 e 3 com relação à presença de adenocarcinoma observou-se uma diferença estatística significante (p=0,0023). A análise de associação entre os grupos 2 e 3 com relação à expressão da COX-2, também evidenciou uma diferença estatística significante (p=0,0018). CONCLUSÃO: O celecoxib teve efeito inibidor da carcinogênese gástrica, induzida pelo refluxo em ratos.

Enterogastric reflux (EGR) is regarded as an unavoidable consequence of distal gastrectomy. We evaluated the efficacy of Roux-en-Y (RY) gastrojejunostomy and Braun enteroenterostomy (BEE) for preventing EGR. Between January 2002 and January 2005, 60 patients who underwent distal gastrectomy for gastric cancer or peptic ulcers were divided into RY, Billroth II reconstruction (BII) without or with BEE (BII+B) according to reconstructive method. After 12 months, EGR and mucosal alterations of the remnant stomach were evaluated using biliary scintigraphy, endoscopy, and histology. Scintigraphy showed fasting and postprandial EGR into the remnant stomach occurred in 5.3% and 21.1% of the RY group, 62.1% and 93.1% of the BII group, and 50.0% and 91.7% of the BII+B group, respectively. Endoscopy showed bile reflux occurred in 15.8% of the RY group, 75.9% of the BII group, and 83.3% of the BII+B group. In addition, the prevalence of Helicobacter pylori (HP) infection in the RY group was less than in the other groups (P

Background It has been suggested that symptoms from bile reflux gastritis are related to the frequency and degree of enterogastric reflux (EGR). Methods Patients with history of upper gastrointestinal surgery or cholecystectomy as well as control patients were studied. Presence of EGR, degree of EGR, and gastric bile emptying time were assessed and quantified via 99mTC scintillation imaging and then compared between symptomatic and asymptomatic patients. Results Patients with vagotomy and pyloroplasty, Billroth I, Billroth II, and cholecystectomy demonstrated statistically higher degrees of EGR compared with controls. Although asymptomatic and symptomatic patients with a history of upper gastrointestinal or biliary surgery demonstrated no statistically significant differences between incidence of EGR and degree of EGR, there was a statistically significant difference in gastric emptying time. Conclusions Delayed gastric emptying time, not frequency or extent of EGR, was associated with the symptoms of bile reflux in patients who had previous upper gastrointestinal or biliary operations.

Enterogastric reflux (EGR) is the reflux of duodenal contents into the stomach. Hepatobiliary scintigraphy provides physiologic assessment of the biliary system and was used to test the hypothesis that presence and timing of EGR may be associated with infusion of sincalide, a surrogate of endogenous cholecystokinin.One hundred fifty-seven hepatobiliary scintigraphy studies were retrospectively reviewed. Data included EGR incidence on initial reports, incidence after masked second reads, and time of EGR onset in relation to sincalide infusion. EGR cases were then classified according to onset on pre-, post-, or both presincalide and postsincalide imaging.Time of EGR onset at 19-24 minutes after start of a 15-min sincalide infusion differed significantly from normal (p0.0001). EGR was initially reported in 14 of 157 cases (8.9%) but found in 38 of 157 cases on masked second reads (24.2%), corresponding to a 15.3% discrepancy rate.The temporal association of EGR onset with sincalide infusion may identify patients with EGR mimicking chronic cholecystitis or biliary dyskinesia. A novel classification schema was therefore developed as a framework for future research, utilizing EGR onset in relation to pre-, post-, or both presincalide and postsincalide imaging as a hypothetical biomarker of clinically significant EGR.

To cast light on tumorigenesis in the remnant stomach after distal gastrectomy for peptic ulcer or gastric cancer, 45 cases in gastroduodenostomy (Billroth I, 17 cases) and gastrojejunostomy (Billroth II, 28 cases) groups were compared for a series of parameters. Cancers in Billroth II were significantly more predominant in the anastomosis area and more frequently associated with Epstein-Barr virus infection. Active gastritis, accelerated epithelial cell turnover (as assessed by measurements of apoptosis and cell proliferation), DNA damage, and foveolar cell hyperplasia were all greater in anastomotic areas after Billroth II than in proximal areas after Billroth II or either area after Billroth I. K-ras mutations were rare, but Epstein-Barr virus infection in cancers was seen frequently in anastomosis cases. In conclusion, active gastritis, possibly induced by enterogastric reflux, is linked to tumorigenesis in anastomosis sites in Billroth II cases.

Background: Recently, gastric stapling with posterior truncal vagotomy has been performed, either by conventional or laparoscopic surgery, as an alternative to highly selective vagotomy and the Taylor procedure for the treatment of chronic duodenal ulcer. Our aim was to investigate the longterm effects after a stapling-modified Taylor procedure, conventional and laparoscopic, on gastric secretion and emptying and on clinical indices and recurrence rates in patients treated for duodenal ulcer before 1994. Study Design: Thirty-one patients, aged 40 to 76 years (mean 53 years), were treated between 1986 and 1993, 21 by conventional and 10 by a laparoscopic stapling-modified Taylor procedure. Outcomes were studied for gastric acid secretion, solid and liquid gastric emptying, euterogastric reflux, endoscopic findings, and clinical indices using the Visick grading. Results: Endoscopy revealed a healing ulcer in 29 patients. Two patients showed signs of chronic ulcerative disease with mild symptoms, without gastritis or pyloric stenosis indicative of progressive ulcerative diathesis, and were classified as Visick III. Twenty-four patients were classified as Visick I and 5 as Visick II. The enterogastric reflux index ranged from 0% to 27%, and basal and peak acid output were 1.5 ± 0.6 mmol H + /h and 12.2 ± 6.4 mmol H + /h, respectively. The half-emptying time of solid and liquid meals was 78 ± 9 minutes and 18 ± 6 minutes, respectively. These results are likely to be similar to those obtained from the series of patients who underwent highly selective vagotomy or Taylor procedure and are close to those achieved in healthy controls. Conclusions: This modification of the original Taylor operation (conventional and laparoscopic) allows a more rapid, technically easier, and radical performance of the operation with excellent longterm results and should be considered an effective alternative for the treatment of duodenal ulcer.

Patients who have undergone partial gastric resections are at an increased risk for the development of cancer in the gastric remnant. The overall risk increases over time and is higher in patients with an initial diagnosis of gastric rather than duodenal ulcer, in men and following partial gastrectomy with Billroth II reconstruction. The site of tumor growth is predominantly in the anastomotic area, but may occur anywhere in the stump. Enterogastric reflux, achlorhydria, bacteria overgrowth, and Helicobacter pylori appear to be the major factors involved in the etiopathogenesis of the gastric stump cancer. Surveillance of these patients with endoscopy and multiple biopsies may provide the means to diagnose tumors at an early stage, but the cost-benefit ratio of surveillance requires further study. Despite the magnitude of alterations in gastric stump mucosa, unfortunately, at this time we do not have good predictors of patients who will develop a cancer.

background Exclusion of the duodenum by means of transection and Roux-Y duodenojejunostomy has been practiced for the treatment of complicated duodenal diverticulum. However, this method does not divert bile away from the diverticulum, hence the possibility of pancreaticobiliary complications is not eliminated. methods Roux-Y Choledochojejunostomy and duodenojejunostomy, for the diversion of bile and food, has been applied for the treatment of pancreaticobiliary complications of duodenal diverticulum in 4 patients. Postoperatively, all patients had endoscopy, HIDA-scintigraphy for the measurement of enterogastric reflux, and assessment of gastric emptying. results One year postoperatively, there were no recurrent symptoms of cholangitis or pancreatitis, no anastomotic ulceration was found on endoscopy, there were no complaints of gastric stasis, and enterogastric reflux was not significant. conclusions Roux-Y Choledochojejunostomy and duodenojejunostomy for the treatment of the complicated duodenal diverticulum is associated with satisfactory results. Postoperative symptoms attributed to anastomotic ulceration, bile reflux, or gastric stasis are also absent.

Distension-evoked gastric reflexes were studied by intracellular recording from circular muscle cells in the gastric fundus, corpus and antrum in the isolated guinea-pig stomach. Localised electrical stimulation, 2 mm circumferential to the recording electrode, evoked inhibitory junctions potentials in all three gastric regions, sometimes followed by depolarisations in the antrum. In the mid corpus, the inhibitory responses were substantially reduced by Nw-nitro-L-arginine (100 microM), unmasking excitatory junction potentials. Residual hyperpolarisations were blocked by apamin (0.5 microM) which also enhanced the amplitude of excitatory junction potentials. These excitatory junction potentials were abolished by hyoscine (1 microM). Thus transmission from inhibitory motor neurons is mediated by both nitric oxide and an apamin-sensitive mechanism. Transmission from excitatory motor neurons to the circular muscle is mediated by acetylcholine via muscarinic receptors. Balloon distension of 10 s duration of the fundus or antrum elicited inhibitory junction potentials in circular muscle cells of the mid corpus. These inhibitory junction potentials were blocked by tetrodotoxin (0.6 microM) and were greatly reduced by Nw-nitro-L-arginine (100 microM). The residual hyperpolarisations were blocked by apamin (0.5 microM). This indicates the presence of ascending and descending inhibitory reflex pathways in the stomach. In 3 out of 7 experiments, following blockade of inhibitory transmission, small nerve-mediated excitatory junction potentials were evoked by antral distension indicating the presence of an additional ascending excitatory reflex pathway. Distension of the corpus elicited prominent inhibitory junction potentials, sometimes followed by large depolarisations, in circular muscle cells in the fundus, but not in the antrum. This suggests that there is also an ascending inhibitory reflex pathway from the corpus to the fundus but no distension-sensitive descending reflex pathway from the corpus to the antrum. These results demonstrate that within the stomach there are reflex pathways which can be activated by localised distension and project at some distance orally and aborally within the gastric wall. It is likely that the inhibitory reflex pathways are involved in gastric adaptive relaxation which occurs when the intact, isolated stomach is distended. The excitatory reflex pathways from the antrum to the corpus are likely to be involved in the intrinsic excitatory reflex responses observed in the isolated intact stomach to distension and thus be involved in the mixing and emptying of gastric contents.

OBJECTIVE AND SUMMARY BACKGROUND: Symptomatic, medically resistant postgastrectomy patients with alkaline reflux gastritis (ARG) have increased enterogastric reflux (EGR) documented by quantitative radionuclide biliary scanning. Even asymptomatic patients after gastrectomy have increased EGR compared with nonoperated control patients. Roux-en-Y biliary diversion, although successfully treats the clinical syndrome of ARG, has a high incidence of early and late postoperative severe gastroparesis, Roux limb retention (the Roux syndrome), or both, which often requires further remedial surgery. As an alternative to Roux-en-Y diversion, this review evaluates the efficacy of the Braun enteroenterostomy (BEE) in diverting bile away from the stomach in patients having gastric operations. Based on previous pilot studies, the BEE is positioned 30 cm from the gastroenterostomy. METHODS: Thirty patients had the following operations and were evaluated: standard pancreatoduodenectomy (8), vagotomy and Billroth II (BII) gastrectomy (6), BII gastrectomy only (10), and palliative gastroenterostomy to an intact stomach (6). All anastomoses were antecolic BII with a long afferent limb and a 30-cm BEE. Four symptomatic patients with medically intractable ARG and chronic gastroparesis had subtotal BII gastric resection with BEE rather than Roux-en-Y diversion. Eight control symptomatic patients and six asymptomatic patients with previous BII gastrectomy and no BEE were evaluated. Radionuclide biliary scanning was performed within 30 days in all patients and at 4 to 6 months in 14 patients. Bile reflux was expressed as an EGR index (%). RESULTS: After operation, 18 of 34 patients (53%) had no demonstrable EGR while in the fasting state for as long as 90 minutes. The range of demonstrable bile reflux (EGR) in the remaining 16 patients was from 2% to 17% (mean, 4.5%). Enterogastric reflux in the 14 control patients (with no BEE) ranged from 5% to 82% (mean, 42%). The four patients with ARG and chronic gastroparesis treated by subtotal gastrectomy and BEE had postoperative EGR of 0%, 2%, 2%, and 4%, respectively. They are asymptomatic with no evidence of bile reflux gastritis. In the 14 patients who had late evaluation, EGR ranged from 0% to 16% (mean, 5.5%). No patient had signs or symptoms of ARG after operation. CONCLUSIONS: Braun enteroenterostomy successfully diverts a substantial amount of bile from the stomach. The ARG syndrome might be prevented by performing BEE during gastric resection or bypass in a variety of operations. Conversion to a BII with BEE may be an alternative to Roux-en-Y diversion in treating medically resistant ARG and subsequent may avoid the Roux syndrome.

There is now a persuasive body of evidence linking Helicobacter pylori infection and peptic ulcer disease. Over 90% of duodenal ulcer and 70% of gastric ulcer patients are infected with H. pylori. Only a minority of infected patients develop ulcers, however, and host cofactors, rather than H. pylori strain, are probably critical to the development of peptic ulcer in infected individuals. Conversely, not all ulcers are associated with H. pylori, and in these cases enterogastric reflux and non-steroidal anti-inflammatory drug ingestion may be important. Eradication of H. pylori dramatically reduces ulcer relapse, effectively curing the disease. Eradication may also accelerate duodenal ulcer healing. Triple therapy with bismuth and antibiotics is effective against H. pylori, but there are problems with side effects, compliance and antibiotic resistance. Encouraging results are emerging on the efficacy and safety of omeprazole/antibiotic combination therapy, and this novel approach to H. pylori eradication is an exciting development. H. pylori has established itself as a pivotal factor in peptic ulcer disease and an effective helicobactericidal regimen is now the most rational and cost-effective treatment.

Inflation of the cardiac stomach of the rainbow trout induced reflex muscular contractions. The stomach then slowly relaxed asymptotically towards its maximum volume. Continued distension caused the stomach to become compliant and this was irreversible within the time course of each experiment (8h). Repeated periods of rest and distension revealed a short-term inhibition of reflex contractions which recovered as resting periods were extended. Sectioning the vagosympathetic trunk did not influence the response to distension. Similar responses occurred in isolated, perfused stomachs. Both tetrodotoxin and atropine plus methysergide induced immediate compliance, suggesting that it was caused by the blockade of enteric excitatory neurones. Atropine alone primarily reduced reflex contractions whilst methysergide completed this suppression and induced profound gastric relaxation. Somatostatin reversibly suppressed reflex contractions whilst vasoactive intestinal polypeptide (VIP) induced gastric relaxation. A model is proposed in which distension initially causes reflex activity via cholinergic and serotonergic nerves, whilst gastric tone remains high. Somatostatin then suppresses rhythmic contractions, whilst VIP suppresses the tryptamin-ergic mechanisms that maintain gastric tone. The rainbow trout stomach possesses intrinsic mechanisms that mimic the extrinsic, nerve-controlled ‘receptive relaxation’ or ‘accommodation’ that follows feeding in higher vertebrates.

A 69-year-old man with remote gastric pull-up was evaluated with a 2-day stress-rest dypiridamole Tc-99m sestamibi myocardial perfusion imaging, where significant tracer uptake was noted in the posterior mediastinum related to enterogastric reflux of sestamibi. These ancillary findings were suggestive of a noncardiac etiology of the patient's atypical chest pain. This case highlights the value of examining the raw projection images for incidental findings that may be present during myocardial perfusion imaging.

Since biliary enterogastric reflux is suggested to eradicate gastric infection with Helicobacter pylori (HP), we have investigated in a prospective randomized study the effect of partial gastrectomy with either Billroth II or Roux-en-Y anastomosis on infection with HP as assessed by the titers of IgG and IgA antibodies against HP in serum. These antibodies were measured by ELISA in serum of 22 patients before and at 10 days and 6, 15, and 24 months after either Billroth II (N = 11) or Roux-en-Y (N = 11) gastrectomy for peptic ulcer. All patients had HP demonstrated in their preoperative endoscopic gastric biopsies. The preoperative serum IgA antibodies against HP (anti-HP IgA) were increased in 20 of the 22 patients (range 0.21-1.69) while the IgG antibodies (anti-HP IgG) were increased in all 22 patients (range 0.38-1.31). Four of the Billroth II patients had clearance of HP from gastric biopsies accompanied by rapid and pronounced decrease of anti-HP IgA. In contrast, the patients with Roux-en-Y gastrectomy and the Billroth II patients with persistent HP infection had no change in anti-HP IgA after surgery. Anti-HP IgG showed variable results in the four patients without gastric HP infection and was not affected by gastrectomy in the patients with persistent HP infection. We concluded that serum anti-HP IgA, but not anti-HP IgG, is helpful in identifying those patients in whom HP is no longer demonstrable after Billroth II gastrectomy. Gastrectomy with Roux-en-Y anastomosis had no effect on gastric HP infection.

To study the effects of chronic bile reflux on the mammalian gastric mucosa, the ferret model was chosen for its practical aptitude and for its similarity to human gastric anatomy and physiology. A technique was first perfected for endoscopically directed gastric mucosal biopsy in the ferret. Subsequently, a surgical model of maximal enterogastric reflux (MR) and a control model of minimal reflux or "nonreflux" (NR) were developed. A stable population of 9 MR and 9 NR ferrets surviving 1-3 years has been established. All 18 animals, plus 6 nonoperative control animals, have undergone multiple repeat endoscopy and gastric biopsy without complication. The surgical and endoscopic techniques, with preliminary findings, are described.

One hundred fourteen patients with suspected acute cholecystitis underwent morphine-augmented cholescintigraphy. The 115 studies were reviewed first to determine the incidence of enterogastric reflux under these conditions. Overall, enterogastric reflux was observed in 85/115 (74%), occurring only after intravenous morphine sulfate in the majority (59%, 50/85). Noted prior to morphine in 41% (35/85), the degree of enterogastric reflux increased noticeably directly following drug administration in over half of these cases. Surgical diagnoses were established in 73/114 (64%) patients as follows: 56 (77%) acute cholecystitis, 15 (20%) chronic cholecystitis, and 2 (3%) another entity (normal gallbladder and tumor encasement). These pathologically proven cases were examined more closely to address the diagnostic significance of enterogastric reflux during morphine-augmented cholescintigraphy. Enterogastric reflux was demonstrated in the majority of not only those with acute cholecystitis (48/56, 86%), but also those with chronic cholecystitis (12/15, 80%). A frequent but nonspecific finding, enterogastric reflux appears to be a pathophysiologic phenomenon that may be enhanced synergistically, at least to some degree, in patients requiring morphine-augmented cholescintigraphy.

The decline in duodenal ulcer disease and the established relation of peptic ulcer to Helicobacter pylori have virtually abolished the need for elective ulcer surgery. However, a substantial proportion of the population around retirement age has previously been subjected to partial gastric resection due to peptic ulcer, and the long-term outcome of these patients is of continuing relevance. Patients subjected to elective surgery could represent a selected group of healthy subjects with a lower overall morbidity, but reports indicate that patients operated on for peptic ulcer have more advanced disease associated with excess smoking and a different pattern of social behavior. The surgical procedure induces enterogastric reflux, leading to profound changes in the remnant mucosa and the formation of carcinogens in the gastric juice. In addition, metabolic abnormalities are common, especially fat malabsorption. Evaluation of the impact of these factors on morbidity and mortality is difficult. Increased mortality in gastrointestinal tumors (especially gastric stump carcinoma), respiratory diseases and other smoking-related malignancies, and suicide are found in the long-term follow-up after partial gastric resection due to peptic ulcer. However, these hazards to life are offset by a decreased mortality in cardiovascular disease. Preventive measures against suicide and especially tobacco smoking are recommended to improve the outcome for this cohort.

Background/Aims: The gastric emptying pattern after esophageal resection and narrow gastric tube reconstruction is determined by multiple factors. One of the possible factors is a disruption in the neurohumoral enterogastric inhibitory reflex. The aim of the present study was to determine the possible alterations of this reflex after esophageal resection and narrow gastric tube reconstruction. Methods: Nine patients each underwent two gastric tube emptying studies, one without and one with high caloric duodenal tube feeding. The dual isotope scintigraphic data were corrected for subject movement, radionuclide decay, downscatter and gamma-ray attenuation. Results: The median gastric tube emptying rate of solid food was 57%/h (range 27–195). The median T½ of liquid food was 67 (range 4–>80) min. Both for solid and for liquid food, the gastric tube emptying patterns without and with duodenal tube feeding were not significantly different. Conclusion: The neurohumoral enterogastric inhibitory reflex is disrupted after esophageal resection and narrow gastric tube reconstruction, which may contribute to disturbed gastric emptying.

1. The coeliac plexus can organize a gastroduodenal inhibitory reflex without action potentials. The involvement of the nitric oxide-cGMP pathway in this reflex was investigated in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and duodenum. Intraluminal duodenal pressures were measured with water-filled balloons. Gastric distension inhibited duodenal motility, thus characterizing a gastroduodenal inhibitory reflex organized by the coeliac plexus. 2. L-Arginine, superfused at the coeliac plexus level, enhanced this reflex, whereas Nomega-nitro-L-arginine (L-NOARG) or 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (carboxy PTIO) reduced or abolished it. Moreover, diethylamine/nitric oxide complex superfused at the coeliac plexus level inhibited duodenal motility in the absence of gastric distension. 3. The effects of nitric oxide were mediated through the activation of guanylyl cyclase, as 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ) reduced or abolished the gastroduodenal inhibitory reflex, whereas zaprinast enhanced it. Moreover, 8-bromo-cGMP and cGMP, superfused at the coeliac plexus level, inhibited duodenal motility in the absence of gastric distension. 4. On the other hand, when perfused at the visceral level, L-NOARG, propranolol plus phentolamine, and guanethidine did not affect the reflex. Thus, neither nitric oxide nor noradrenaline could be the transmitters released at the muscular level to induce this reflex. 5. Our study demonstrates that the gastroduodenal inhibitory reflex, which is organized by the coeliac plexus without action potentials, is induced by the release within the plexus of nitric oxide acting on the cGMP pathway. These results provide new insights into the control of digestive motility by the prevertebral ganglia.

Objective: To design an operation to prevent enterogastric reflux of bile that will not interfere with gastric or proximal intestinal motility and that will be applicable in patients with primary alkaline reflux gastritis, various prior ulcer operations, and previous corrective operations for enterogastric reflux. Design: A nonrandomized, prospective review of 27 patients with enterogastric reflux operated on between 1991 and 1995. Setting: A midwestern medical school and 400-bed tertiary referral center, adult hospital. Patients: Twenty-seven patients with symptoms compatible with enterogastric reflux, primary or secondary to ulcer operations, or with Roux-en-Y limb stasis following attempts to correct alkaline reflux gastritis. Interventions: An operation designed to reestablish gastroduodenal continuity by converting previous procedures such as Billroth II gastrectomy and Roux-en-Y gastrojejunostomy to a Billroth I gastroduodenostomy, and by diverting bile away from the stomach by end-to-side choledochojejunostomy by means of a Roux-en-Y limb of 35 to 40 cm. Main Outcome Measures: Resolution of the preoperative symptoms of pain, nausea, and bilious vomiting in patients with enterogastric reflux, and elimination of the Roux stasis syndrome as well as prevention of future enterogastric reflux in patients undergoing conversion from Roux-en-Y to Billroth I. Serial evaluation of gastric emptying after conversion to a Billroth I configuration to determine whether dysmotility is improved or eliminated. Results: Symptoms were completely resolved in 22 of the 26 surviving patients, with follow-up of 6 months to 4 years. None of the 26 patients have had any bilious vomiting postoperatively. Roux-en-Y stasis has been corrected when due to a mechanical problem (eg, strictures, marginal ulcers), although thus far normal gastric emptying has not been observed in all of these multiply surgically treated patients. Conclusions: Enterogastric reflux is common following most ulcer operations. Attempted correction of this problem may result in other difficulties, including delayed emptying due to Roux-en-Y stasis. The fact that most patients with enterogastric reflux are female suggests that this condition is related to disordered motility; therefore, vagal interruption and major gastric resections should be carefully considered to avoid future disabling problems. Arch Surg. 1997;132:245-249

Laser Doppler flowmetry (LDF) was used for endoscopic measurement of regional blood flow in 20 patients who had undergone previous gastric resection for peptic ulcer. Twenty-five patients with intact stomach and normal endoscopic findings were used as controls. In resected patients, the degree of enterogastric reflux gastritis was assessed by subjective grading and by morphological examination of biopsies from the region of the gastroenterostomy. In patients with an intact stomach, the average blood flow was significantly higher in the body of the stomach compared to the antrum (p < 0.001), without any significant differences between the greater and lesser curvature. In resected patients, the average blood flow in the gastric body remnant was markedly higher than in the region of the gastroenterostomy, but also significantly higher than the corresponding area of the gastric body in patients with an intact stomach (p < 0.01). The degree of gastritis in the region of the stoma of resected patients was often overestimated on subjective endoscopic assessments compared to morphological biopsy examinations. The degree of histological gastritis was not significantly correlated to blood flow levels of the gastroenterostomy. It is concluded that low gastric wall perfusion, impeding mucosal defense, does not seem to be a major factor in the development of enterogastric reflux gastritis in the resected stomach.

A review is presented of the design of radiolabelled test meals for the evaluation of gastrointestinal function, including oesophageal transit, gastro-oesophageal reflux, gastric emptying, enterogastric reflux and transit through the whole bowel. Descriptions of different systems are presented, together with validations of the procedures used. Published methods for assessment of oesophageal transit show a marked degree of consistency, whereas gastric emptying studies employ a wide range of both liquid and solid test meals. Recommendations are made concerning the optimal system for investigation of each part of the gastrointestinal tract, but whichever system is adopted, it is important to employ some validation procedures, and to establish normal ranges in the population under study.

The mechanisms involved at the prevertebral ganglionic level in a gastroduodenal inhibitory reflex were investigated in the rabbit on an in vitro preparation of the coeliac plexus connected to the stomach and duodenum. Intraluminal gastric and duodenal pressures were measured using water-filled balloons. Gastric distension inhibited duodenal motility via a nerve reflex which was abolished by section of the nerves connecting the coeliac plexus to the viscera. Superfusion of the coeliac plexus with a low Ca 2+ -high Mg 2+ solution abolished the gastroduodenal inhibitory reflex, indicating a synaptic link at the ganglion level. The reflex was unaffected by superfusion of the coeliac plexus with hexamethonium and tubocurarine, ruling out a nicotinic mechanism. The reflex persisted when the coeliac plexus was superfused with tetrodotoxin or when the nerves connecting the coeliac plexus to the viscera were superfused with a Na + -free solution; these results indicate that the reflex does not involve sodium-dependent action potentials. Moreover, superfusion of the nerves connecting the coeliac plexus to the viscera with a calcium blocker or with a Ca 2+ -free solution also failed to abolish the reflex, suggesting that calcium-dependent action potentials are not involved. Our study demonstrates that a gastrointestinal inhibitory reflex via the coeliac ganglion is not based on fast synaptic inputs or action potentials. These results provide new insights concerning the physiology of the sympathetic prevertebral ganglia.

A new technique for the long-term ambulatory detection of enterogastric and nonacid gastroesophageal reflux has been conceived, developed, and validated. It is based on the use of a fiberoptic sensor that utilizes the optical properties of bile. In vitro studies have shown good precision, good stability, sensitivity of 2.5 mumol/liter bilirubin concentration, as well as a useful working range of 2.5-100 mumol/liter bilirubin concentration. In vivo studies have been performed in 29 subjects. Simultaneous gastric aspirations have allowed a comparison of fiberoptic system measurements both with spectrophotometric analysis and bile acid concentrations of corresponding gastric juice samples. Linear correlations were shown between fiberoptic assessment and both spectrophotometric and bile acid concentration findings (P < 0.01). Simultaneous assessment of reflux with the fiberoptic system and cholescintigraphy has shown a 92.9% concordance as regards the presence or absence of reflux. Present results imply that the fiberoptic system is an important tool for the understanding of the clinical relevance of enterogastric and nonacid gastroesophageal reflux.

Neural and endocrine pathways mediate the inhibitory effects of intestinal fat on gastric acid secretion. To study whether vagal and/or spinal afferent nerves contribute to the neural component of the enterogastric reflex, the sensory neurotoxin capsaicin was applied topically either to the vagus nerves bilaterally or to the celiac-superior mesenteric ganglia in rats with chronic gastric and duodenal fistulas. In lightly restrained, awake rats acid secretion was stimulated for 2 h by continuous intragastric perfusion with 8% peptone and was measured by extragastric titration to pH 5.5. Duodenal lipid perfusion (0-20%) during the 2nd h caused inhibition of peptone-stimulated acid output. Acid output was inhibited by 81% during 5% lipid perfusion of the duodenum and was restored after capsaicin treatment of the vagus nerves. In contrast, capsaicin treatment of the celiac ganglion did not alter the acid inhibitory response to any dose of intestinal lipid. Basal and maximum acid outputs were not significantly different among rats treated by either method with capsaicin. The neural component of the enterogastric reflex in awake rats is mediated in part by a capsaicin-sensitive, vagal-afferent neural reflex.

Without considering the possibility of any alternative, nineteenth-century physi­ologists assumed that gastric secretion is exclusively under nervous control, and that it is under reflex control was amply demonstrated toward the end of the century by Ivan Petrovich Pavlov and his students. The doctrine of exclusive nervous con­trol was shattered by William Bayliss and Ernest Starling’s discovery on the after­noon of 16 January 1902 that a “chemical reflex” originating in the intestinal mucosa mediates stimulation of pancreatic secretion by acid in the upper intestinal tract. Spurred by this discovery, J. S. Edkins thought that he had identified a cor­responding humoral agent, gastrin,in the antral mucosa that mediates stimulation of acid secretion in the stomach. The twin discoveries that histamine is a powerful stimulant of acid secretion and that histamine is present in tissue extracts raised doubts about the reality of gastrin. Confusion on this point continued until just before the Second World War, when Simon Komarov presented some proof of the existence of gastrin, and beginning shortly after the end of the war, study of stim­ulating and inhibiting hormones dominated the problem of the control of gastric secretion. Toward the end of the period under consideration here, the interaction of nerves, histamine, and hormones in control of gastric secretion began to be understood.

In 28 controls and 142 patients subjected to a variety of antiulcer procedures, the enterogastric reflux (EGR) was quantitated by 99mTc-HIDA scintigraphy and expressed as the EGR index on 229 different occasions. The EGR index was calculated according to two different formulas: one based on the maximal radioactivity over the gastric area as a percentage value of the total abdominal activity (EGR-Im) and the other based on the relative maximal radioactivity over the gastric area as a percentage value of the relative hepatobiliary activity (EGR-It). There was a significant positive correlation of values between the two methods (P less than 0.0001). In patients with an EGR-Im greater than 20% or EGR-It greater than 57% and postgastric surgery symptoms some of the symptoms were attributed to EGR, an antireflux procedure is expected to relieve those symptoms. Sixteen of these patients underwent Roux-en-Y gastrectomy and their preoperative symptoms were relieved.

This study evaluates enterogastric reflux (EGR) levels in patients with and without symptoms of postoperative alkaline reflux gastritis (PARG) after gastric surgery. The bile acids (BA) present in the gastric juice were quantified by thin-layer chromatography and spectrofluorometry. The mean BA concentration for controls was 2.25 mumol reflux/hour, for 15 asymptomatic patients 47.94 and for 15 patients with symptoms of PARG 125.79. After biliary diversion by a Roux-en-Y anastomosis in the latter, their BA in 13 of these patients after surgery, and relapsed in only one during a 4-year follow-up. The remaining two patients had the lowest preoperative BA levels in this group. These results indicate that EGR is increased after gastric surgery more markedly indicated that EGR is increased after gastric surgery more markedly in patients with symptoms of PARG, and that patients who have high levels of EGR (more than 80 mumol BA reflux/hour) clearly benefit from biliary diversion.

Enterogastric reflux has been implicated as a possible etiologic mechanism in gastritis both after partial gastrectomy and in those with an intact pylorus. We studied the effects of cimetidine on bile acid concentration and composition by high-performance liquid chromatography. The gastric aspirates collected for this study came from 27 prospectively randomized patients receiving intravenous cimetidine (200 mg every 6 hours) and 25 patients given a placebo. Total bile acid concentration of aspirates was determined spectrophotometrically. Marked differences were noted in conjugated bile acids. Glycochenodeoxycholic acid, a toxic dihydroxy bile acid, was decreased after, cimetidine compared with results from the placebo. The ratio of less toxic trihydroxylated to more toxic dihydroxylated bile acids was significantly increased. Enterogastric reflux itself seemed unaltered by cimetidine; likewise, the concentration of total bile acids in the cimetidine group was similar to that among patients receiving placebo. These changes in bile salt composition with cimetidine may help explain its salutary effects in gastritis, over and above its ability to reduce gastric hydrogen ion secretion.

Various problems are encountered in measuring gastric emptying, especially relating counts to the volume of meal remaining in the stomach. We have developed a method which has been validated against aspiration of the stomach. In gastric ulcer patients, however, the stomach is large and overlaps the bowel. Results of gastric emptying studies in patients who have had surgery for peptic ulceration show that impaired gastric emptying is related to the extent of vagotomy and pyloric surgery. We have examined the pattern of biliary excretion of iminodiacetic acid derivatives and related enterogastric reflux to the amount of bile in the stomach as determined by aspiration. However the reproducibility is only 75% probably due to day to day variation in its occurrence. The incidence of reflux in control subjects and in those with peptic ulcer is discussed, as is its relationship to the extent of vagotomy and the length of Roux-en-Y loops. Finally the diagnosis of biliary atresia using a similar radiopharmaceutical is described. It has been suggested that a high liver to heart ratio excludes the diagnosis of atresia, but we have failed to confirm this finding.

We evaluated the significance of bile seen in the stomach at the time of endoscopy. Twenty-three percent of 110 consecutive patients undergoing elective panendoscopy were found to have bile in their stomachs. Gastric biopsies were obtained from these patients. To assess the significance of bile reflux, the patients underwent a quantitative gastric bile analysis on two separate days. On day 1, gastric juice was aspirated by nasogastric suction, and bile acid concentrations were measured. On day 2, bile reflux into the stomach was quantitated by scintiscan measurement of gastric nucleotide after intravenous administration of 99mTc-DISIDA. Approximately half the patients with bile reflux showed histologic evidence of mucosal injury. However, fewer than half with histologic injury had significant bile reflux when measured by quantitative methods. There was no correlation among the gastric bile acid concentration, degree of histologic injury, or severity of endoscopic changes. We conclude that finding bile reflux at endoscopy is probably of no clinical significance.

1. Gastric relaxation, vasodilatation and vasoactive intestinal peptide (VIP) output from the stomach in response to stimulation of the central end of the cut vagus nerve were studied in anaesthetized dogs. 2. Central vagal stimulation (10 Hz, 40 V, 0.5 ms) normally produced a non-adrenergic, non-cholinergic (NANC) gastric relaxation via a vago-vagal reflex. It also caused an increase followed by a decrease in gastric blood flow. 3. The increase in blood flow was attributable to a NANC gastric vasodilatation via a vago-vagal reflex and the subsequent reduction in blood flow was decreased by splanchinicotomy. All these gastric and vascular responses were abolished by hexamethonium. 4. The gastric relaxation and vasodilatation induced by the vago-vagal reflex had similar stimulation frequency-response and pulse duration-response relations. 5. Central vagal stimulation caused an increase in gastric venous VIP output which was abolished by vagotomy or hexamethonium but unaffected by splanchnicotomy. 6. VIP injected into the gastric artery mimicked the gastric relaxant and vasodilator responses to the vago-vagal reflex. 7. We conclude that the intramural NANC inhibitory nerves activated by the vago-vagal reflex release VIP which causes both gastric relaxation and vasodilatation.

Initially, scintigraphy was established as a valid method for detecting and quantitating enterogastric reflux. A new, tubeless technique for the measurement of enterogastric re flux was developed. 99mTc bound to [(2,6 dimethylphenylcarbamoylmethyl) iminodiacetic acid] (5 mCi) was administered intravenously to visualize the liver and biliary tract. One hour later, a standard liquid meal labeled with 111 In bound to diethylene-triamine penta-acetic acid (250 μCi) was given. The 99mTc and 111In activities were recorded simultaneously for 1-min periods at 15-min intervals for 2 hr over liver, gallbladder, and gastric areas of interest. Enterogastric re flux indices were determined. Ten normal subjects and 13 patients with vagotomy, hemigastrectomy, and Bilroth II gastrojejunostomy were evaluated. The enterogastric reftux index in asymptomatic postsurgical patients was increased significantly to 24.6 ± 4.7 compared with 8.2 ± 6.0 (P

Plasma gastrin concentrations and gastric acid output were measured during graded balloon distention of the gastric fundus and body in 20 patients with duodenal ulcer. Acid output rose stepwise with increasing distention volumes but plasma gastrin remained unchanged. During intragastric neutralization in 5 of these subjects, fundic distention did not elicit a significant rise in plasma gastrin, whereas the acid response was similar to that observed in the control study when the gastric contents were acid. In 8 of the 20 patients, proximal gastric vagotomy profoundly suppressed the acid response to fundic distention. Basal plasma gastrin concentrations were elevated after vagotomy, but were unchanged during graded fundic distention. The results suggest that neural reflex activation of the oxyntic glands is the main mechanism by which fundic distention stimulates acid secretion in man. The failure of fundic distention to release gastrin does not, however, completely rule out the existence of an oxyntopyloric distention reflex for gastrin release in man. Fundic distention in man seems to both stimulate acid secretion and induce an inhibitory mechanism acting on acid secretion. This inhibitory mechanism may, purely speculatively, also mask the effect of an oxyntopyloric reflex for gastrin release. The present study and earlier work suggest that in man distention of the stomach is a poor stimulus for release of gastrin, regardless of whether the pyloric or the oxyntic gland area, or both, are distended.

Complete gastric emptying time using barium sulfate mixed with commercial canned dog food was measured radiographically in 29 mature mixed breed dogs before and 3 to 4 weeks after Fredet-Ramstedt pyloromyotomy (FRP) (6 dogs), Heineke-Mikulicz pyloroplasty (HMP) (6 dogs), Finney pyloroplasty (FP) (6 dogs), Jaboulay's gastroduodenostomy (JG) (6 dogs), and antral gastrojejunostomy (AG) (5 dogs). The dogs were observed for clinical evidence of side effects. Postoperative endoscopic examination and double contrast gastrography were performed to subjectively evaluate the diameter of the gastrointestinal communication and the amount of enterogastric reflux. Although none of the procedures significantly (p less than 0.05) altered gastric emptying time, the overall tendency was toward slowing down gastric emptying time. The severity of gastrointestinal side effects and enterogastric reflux appeared to be related to the size and/or location of the gastrointestinal opening.

Excessive Enterogastric reflux following partial gastrectomy is believed to be responsible for bilious regurgitation, vomiting, nausea, and epigastric pain. At endoscopy, striking erythema and inflammatory changes of the gastric mucosa may be seen. The nonsurgical treatment for this syndrome is unsatisfactory. Because of the potential pathogenetic role of regurgitating bile acids, lysolecithin, and pancreatic secretions, it seemed relevant to find out whether prostaglandin E2 (PGE2) in a dose of 0.5 mg qid could protect the gastric mucosa from further damage and thereby lead to symptomatic improvement. The results of this controlled doubled-blind crossover trial, comparing PGE2 and placebo, in the treatment of postgastrectomy reflux gastritis reveal no significant differences between PGE2 and placebo with regard to symptoms, endoscopic features, and histologic evidence of inflammatory changes. Thus, prostaglandin E2 in the dose used appears incapable of improving postagastrectomy reflux gastritis in patients with mild to moderate degrees of this entity.

We studied the effect of graded antral distension on gallbladder contraction both when gastrin release was promoted (alkaline distension) and when gastrin release was blocked (acid distension) in five dogs provided with innervated antral pouch, chronic bile fistula and gastric fistula. Graded distension of the antrum caused graded gallbladder contraction as evidenced by bilirubin output even when gastrin release was completely suppressed. This nongastrin mechanism of gallbladder contraction is abolished by parenteral atropine and by transthoracic truncal vagotomy. These observations provide evidence for a cholinergic, pyloro-cholecystic reflex for gallbladder contraction that is dependent on intact long vagal pathways. Similar reflex mechanisms have been shown to be initiated by antral distension and to cause pancreatic enzyme secretion (pyloro-pancreatic reflex) or acid secretion from the oxyntic gland area of the stomach (pyloro-oxyntic reflex). It would appear, therefore, that the antrum plays a central role in the integration of upper gastrointestinal function not only through the hormone gastrin but also through neural reflex mechanisms.

A total of 98 patients, who had undergone gastric surgery (23), or who had peptic ulcers (56), or who had normal endoscopic findings (19) underwent gastric biopsy, together with measurement of pH and total bile acid concentration, in their fasting gastric juice. The biopsy specimens were stained by the Warthin-Starry method for Campylobacter like organisms and were also graded "blind," as described in the preceding paper, for the five features that we believe may constitute the histological picture of reflux gastritis. The individual grades were added together to give a composite "reflux score" (0-15) for each patient. We found a notable association between the absence of Campylobacter like organisms and previous surgery for peptic ulceration, high reflux scores (greater than 10), hypochlorhydria (pH greater than or equal to 4), and increased bile acid concentrations (greater than or equal to 1 mmol/l) in the stomach. These findings further support our contention that reflux gastritis represents a distinct histopathological entity causally related to the effects of enterogastric reflux on the gastric mucosa and suggest that there may be two major categories of chronic gastritis: chronic superficial, or atrophic gastritis related to Campylobacter like organisms and reflux gastritis. Our data also imply that patients with peptic ulceration may, after gastric surgery, revert from being positive for these organisms to being negative and may undergo a possible transition from Campylobacter related chronic gastritis to reflux gastritis.

Bile reflux gastritis is a disabling postgastrectomy condition characterized by abdominal pain, bilious vomiting, and weight loss. The syndrome appears to be caused by free enterogastric reflux of bile and other proximal small bowel constituents. Endoscopic confirmation of bile reflux and documentation of gastritis support the diagnosis but are not specific for it. Results of medical therapy with chelating agents or drugs that promote gastric motility have been disappointing. Diet and antacids frequently aggravate symptoms. The only effective treatment is surgical diversion of bile away from the gastric mucosa. During a recent seven-year period, 15 patients had diversionary operation for bile reflux gastritis diagnosed by history and endoscopic findings. Before operation, medical management had failed to yield improvement in any case. After operation, all patients showed improvement, and pain was relieved in 85%. Based on our experience, we conclude that current medical therapy may alter but not cure symptoms of bile reflux gastritis; Roux-en-Y diversion is the treatment of choice in patients with persistent symptoms; and delayed gastric emptying is a common complication after the Roux-en-Y procedure, but in our series, the incidence was reduced by using the Tanner 19 modification. New cytoprotective agents that may offer an alternative to operation are currently being studied.

Gastric responses to electrical stimulation of the vagus and splanchnic nerves and to esophageal distension were observed in studies of the reflex control of the gastric motility in anesthetized guinea pigs in vivo. The gastric motility was inhibited by both vago-vagal and splanchno-vagal reflexes through the activation of non-adrenergic inhibitory nerve fibers and by splanchno-splanchnic reflex through the inactivation of the intramural cholinergic excitatory neurons. Distension of the lower esophagus caused a relaxation of the stomach which was mediated by an intrinsic reflex via intramural non-adrenergic inhibitory neurons. Furthermore, stimulation of the splanchnic nerve innervating the stomach seems to activate adrenergic inhibitory, cholinergic excitatory and probably some non-adrenergic inhibitory fibers.

In order to identify the mechanisms responsible for the inhibition of gastric secretion observed during acidification of the duodenal bulb, dogs were prepared with a gastric fistula (GF), Heidenhain pouch (HP), and pancreatic fistula. The duodenal bulb (5 cm) was separated from the stomach by a mucosal septum at the pyloric end and was brought to the surface in a mucocutaneous fistula distally. After the first series of experiments were completed, the dogs were reoperated and the duodenal bulb was completely separated from the stomach. The experiments were then repeated. Perfusion of the innervated duodenal bulb with 8 mEq of HC1 per hr resulted in 50% inhibition of pentagastrin (2 μg per kg-hr) -induced acid secretion from the GF and slight stimulation of pancreatic volume, bicarbonate, and protein output. Acid and pepsin secretion from the HP were unchanged by acidification of the bulb. A small dose of synthetic secretin (0.2 U per kg-hr) increased pancreatic secretion more than did bulbar acidification but did not inhibit acid secretion. A larger dose of secretin (1.6 U per kg-hr) caused 50% inhibition of acid secretion from both the GF and HP. Following the surgical separation of the duodenal bulb from the pylorus, acidification of the bulb failed to inhibit gastric secretion from the GF as well as from the HP. We interpret these results as evidence for the existence of a neural reflex, triggered by acid in the duodenal bulb, and inhibiting gastric secretion. Earlier studies by several groups have shown that acidification of the bulb inhibited HP secretion, thus indicating a hormonal mechanism. We cannot explain the failure to find evidence of such a mechanism in this study.

Impulses have been recorded from single vagal gastric motor axons in sheep during reflex gastric contractions. Several different patterns of activity associated with contractions of different parts of the stomach were found. Each unit had a stable and characteristic pattern of discharge. The discharge of a unit could be modified by a general excitatory stimulus e. g., acidification of the gastric contents or by afferent “feed-back” from the part of the stomach that was contracting.

In acute experiments on chloralosed cats gastric motility was recorded with a rubber balloon system kept at constant intragastric pressure under experimental conditions not requiring abdominal surgery.-Electric stimulation of the central end of either a small vagal branch at the level of the diaphragm or of one vagal nerve at the level of the neck, while the opposite vagal nerve was left intact produced profound reflex relaxation of the stomach. Also the efferent pathway of the relaxatory reflex was in the vagal nerves.-The reflex relaxation persisted after administration of atropine, which shows that it was not due to reflex suppression of prevailing activity of the vagal cholinergic motor fibres. It was also independent of adrenergic mechanisms, since it persisted after administration of guanethidine in doses known effectively to block the adrenergic intestino-gastric inhibitory reflex. This vago-vagal relaxatory reflex response thus showed the same characteristics as the gastric response elicited by efferent stimulation of the high-threshold vagal relaxatory fibres.-It is concluded that this vago-vagal reflex originates, at least partly, from abdominal structures, with the efferent pathway consisting of the relaxatory, high-threshold fibres producing pronounced gastric relaxation. This vago-vagal relaxatory reflex may be involved in receptive relaxation of the stomach.