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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.

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.

Recurrent vomiting with failure to thrive is a common problem in neurologically impaired children. Many undergo fundoplication to control the underlying gastro-oesophageal reflux. The results of surgery are not always satisfactory and post-operative retching may be a major problem - a symptom indicative of activation of the emetic reflex. An animal model of antireflux surgery has been developed and used to investigate the effects of such surgery upon the emetic reflex and vagal influences on gastric motility. Following surgery, animals responded to a previously subemetic dose of a centrally acting opiate receptor agonist (loperamide), suggesting that fundoplication may sensitize the emetic reflex. A gastric vago-vagal reflex (tonic inhibition of corpus tone) and responses to direct stimulation of vagal motor efferents (both cholinergic and nonadrenergic noncholinergic responses) were not significantly affected by antireflux surgery. Mechanisms by which neural damage may sensitize the emetic reflex are discussed, together with the possible clinical implications for the management of post-operative symptoms in neurologically impaired children.

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.

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.

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.

Hepatobiliary imaging with Tc-99m-HIDA was performed on a 57-year-old woman with partial situs inversus. Scans showed reflux of radioactive material into the right side of the stomach.

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.

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.

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.

Cystic changes of gastric mucosal glands have been described mainly after gastric operations, and like intestinal metaplasia and dysplasia, they may represent a premalignant condition. Their association with gastritis raises the possibility of their being secondary to the inflammatory process. Enterogastric reflux of duodenal contents, local chronic ischemia, and inflammatory reaction as a result of gastric surgery and suture at gastroenterostomy have been considered responsible for this lesion. In 18 of 157 consecutive patients (11.5%) who underwent endoscopic gastric biopsy within a year we found cystic changes of gastric mucosal glands. Cystic changes were present in 43% of 30 patients after gastric operation for duodenal ulcer disease, within an average of 8.4 years in contrast to only 4% of patients with an intact stomach. This change is statistically significant (Z = 1.97, (p less than 0.05) and suggests that there is a cause-and-effect link between the operation and the development of cystic lesions. In three patients we traced the original operative specimen, and in none did we find cystic changes. All the cases were associated with chronic gastritis; mild dysplasia was found in four (22%). The cystic glands were shown (by alcian blue-periodic acid-schiff staining) to secrete neutral mucin like normal gastric glands, and unlike dysplastic glands or intestinal metaplasia where acid mucin is characteristic. Thus, our findings suggest an inflammatory cause for the cystic glandular change (reactive, hyperplastic change of glands), and suggest that it is probably not a preneoplastic state.

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.

Postoperative paralytic ileus is in part mediated by the sympathetic gastrointestino-gastrointestinal (GI-GI) reflex. The modulation of this reflex by epidural fentanyl (50 micrograms) was studied in chloralose-anesthetized, ventilated cats. The vagi were cut in the neck but could be efferently stimulated. Gastric volume, arterial pressure and heart rate were followed and the GI-GI reflex was elicited by intestinal distension, mesenteric afferent nerve stimulation or heating or capsaicin administered intra-arterially to an intestinal loop. Epidural fentanyl enhanced the gastric contraction response to efferent vagal stimulation and considerably counter-acted the GI-GI reflex inhibition of vagally induced tone. These effects were reversed by epidural naloxone (10 micrograms). In contrast, 50 micrograms of fentanyl i.v. only enhanced the effect of vagal stimulation but had no influence on the inhibitory GI-GI reflex responses. Apparently, epidural fentanyl may inhibit the GI-GI reflex by a spinal point of action.

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.

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.

1. In the urethane anaesthetized ferret gastric inflation with 50 ml. 0.9% NaCl at a rate of 10 ml./min evoked large gastric contractions. The threshold of intragastric pressure required to elicit the reflex was 3.1 +/- 0.5 cmH2O. 2. The response was enhanced by splanchnic nerve section and markedly reduced by bilateral cervical vagotomy, indicating that both afferent and efferent limbs of the reflex were in the vagus nerves. 3. By using a transected stomach it was shown that distension of the corpus evoked contractions of the antrum that were abolished by vagotomy. 4. The reflex activation of antral motility by vagal afferents with receptive fields in the corpus may play a physiological role in gastric emptying.

Reflex responses of the lower oesophageal sphincter (l.o.s.) to distension of the stomach were studied by electromyographic and manometric techniques. Distension of the fundus and gastric antrum by inflation of a balloon elicited two types of reflex response of the l.o.s. Thus, whereas excitatory responses were recorded following slight distensions, larger distensions resulted in inhibitory responses. Splanchnic fibres and sympathetic fibres originating from the stellate ganglion, as well as vagal fibres served as the efferent pathways for the excitatory reflex response. The efferent pathways for the inhibitory response involved only vagal fibres.

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.

Post-gastrectomy symptoms of dyspepsia, epigastric pain, nausea, and bilious vomiting have been ascribed to duodenogastric reflux. A non-invasive method, using the radiopharmaceutical technetium-99m p -butyl-iminodiacetic acid, has been developed to observe biliary excretion scintigraphically and to monitor its excretion. 10 controls and 45 patients after stomach operations were given the radiopharmaceutical intravenously and were scanned every 5 min for an hour, after which the site of the stomach was determined by asking the patient to drink technetium-99m in solution. Reflux was noted in 1 control, m 4 of 13 patients after highly selective vagotomy, in 8 of 17 patients following truncal vagotomy and pyloroplasty, and in all of 15 patients after gastrectomy. The mean quantities of reflux in these four groups were 5%, 3·75%, 12·4%, and 44%, respectively. The study confirms that post-gastrectomy patients are more prone to enterogastric reflux and suggests that this form of scintigraphy may produce valuable clinical information.

Thirty-six asymptomatic patients at a mean time interval of 12.7 years after gastric surgery were assessed by endoscopy, intragastric pH measurement, and multiple biopsy at a single endoscopy and by99mTc Imino Diacetic Acid (HIDA) scanning for enterogastric reflux: 9 patients had had Polya gastrectomy, 10 patients truncal vagotomy and antrectomy (Billroth I anastomosis), 9 patients truncal vagotomy and pyloroplasty, and 8 patients proximal gastric vagotomy. In the resection group the 9 patients with histological evidence of mucosal risk factors (dysplasia, chronic atrophic gastritis, intestinal metaplasia) had a fasting intragastric pH of more than 4. However, fasting pH was of no value in predicting the occurrence of risk factors after vagotomy (6 of 17 patients). The amount and duration of enterogastric reflux as measured by HIDA scanning over 50 minutes did not correlate with risk factors after resection. The amount and duration of reflux after vagotomy were greater in the patients with risk factors but were not discriminatory. We conclude that HIDA scanning is of little value as a screening procedure and that single sample pH testing is useful only in patients after a gastric resection.

Reflux of upper intestinal content to the gastric remnant after gastric resection is common and may cause damage to the gastric mucosa, resulting in gastritis, gastric ulcer, and possibly dysplasia. Different surgical procedures have been proposed to prevent reflux, among them Roux-en-Y diversion. In this study we have compared antrectomy followed by gastroduodenostomy (BI) with antrectomy followed by Roux-en-Y anastomosis with regard to enterogastric reflux. Reflux was recorded by cholescintigraphy, using a new method for quantification. In all patients biopsy specimens were taken for histopathological evaluation at gastroscopy. Twenty-seven patients were studied, 11 with gastroduodenostomy and 16 with Roux-en-Y diversion. All patients in the gastroduodenostomy group had reflux, compared with four in the Roux group (p less than 0.001). Under the light microscope all patients in the BI group showed a moderate to severe degree of inflammation compared with only seven in the Roux-en-Y group (p = 0.028). Our results show that Roux-en-Y drainage effectively diminishes reflux and may be an explanation for the lower extent of mucosal damage in these patients.

The aim of this study was to assess the possibility of detecting enterogastric reflux (EGR) by 75Se-HCAT cholescintigraphy. The lowest detectable activity in the gastric area at different concentrations of the radiotracer in the gallbladder was preliminary measured both in a plastic phantom and in an in vivo model. Ten patients were studied after a single oral administration of 1480 KBq 75Se-HCAT. Gamma camera imaging was carried out for five consecutive days during both fasting and after meal ingestion. In our in vivo model an EGR corresponding to 1% of gall-bladder content on day one and 8% on day five was detected. In three out of five patients in whom bile was present in the stomach at endoscopy, 75Sc-HCAT cholescintigraphy demonstrated an EGR, while in three out of five patients in whom endoscopy was negative, 75Se-HCAT cholescintigraphy detected EGR either during fasting or after meal ingestion. As EGR is not constant, 75Se-HCAT may be a useful tracer of bile to detect EGR over a prolonged period of time and in different physiological conditions.

In order to prospectively determine the effect of gastrectomy with or without enterogastric reflux on serum pepsinogen concentrations, serum pepsinogen A, serum pepsinogen C and the pepsinogen A:C ratio were measured before, and 10 days and 6, 15 and 24 months after 2/3-3/4 distal gastrectomy in peptic ulcer patients with primary Roux-en-Y diversion (n = 11) or Billroth II reconstruction (n = 11). Gastrectomy induced early decreases in serum pepsinogen A from 100 +/- 12 to 66 +/- 7 micrograms/l (p less than 0.05) and from 111 +/- 11 to 82 +/- 20 micrograms/l (p = 0.05), serum pepsinogen C from 49 +/- 6 to 29 +/- 5 micrograms/l (p less than 0.05) and from 54 +/- 9 to 40 +/- 11 micrograms/l (p = 0.10) in patients with Roux-en-Y and Billroth II gastrectomy, respectively, but did not influence the pepsinogen A:C ratios. Serum pepsinogen A and the pepsinogen A:C ratio continued to decrease 6 months after surgery but no further significant reductions were observed 15 and 24 months postoperatively. Serum pepsinogen C concentrations did not significantly change during postoperative follow-up. Analyses of variances of serum pepsinogen A and the pepsinogen A:C ratio showed that the type of operation had no significant effect on the postoperative course. It is concluded that gastrectomy leads to early decreases in serum pepsinogen A and pepsinogen C levels followed by progressive further reductions of serum pepsinogen A and the pepsinogen A:C ratio for a period of 6 months postoperatively. These postoperative changes of serum pepsinogens are not due to increased enterogastric biliary reflux.

The reflex effects of distension and contraction of the gastric antrum on corpus-fundus motility were studied in anesthetized cats. Besides a vagally mediated reflex corpus-fundus relaxation, antral distension elicited a prompt reflex inhibition of corpus-fundus contractions that was present also after vagotomy. In vagotomized animals this inhibitory reflex persisted also after cervical spinal cord transection, but was abolished by spinal anrsthesia or by guanethidine. Stepwise increases of antral distension revealed that the reflex corpus-fundus inhibition appeared already at distending pressures of 5–10 cm H2O, then increased in a graded fashion and could be maintained for at least 10 min if a steady distension was applied. Also “isometric” antral contractions were effective in eliciting the reflex corpus-fundus inhibition. — It is concluded that activation of slowly adapting “tension receptors” in the antral gastric wall inhibits gastric (corpus-fundus) motility via a spinal reflex mechanism, mediated by splanchnic adrenergic fibres that seem to suppress the intramural excitatory cholinergic neurons. This gastro-gastric adrenergic inhibitory reflex seems to be activated concomitantly with a vago-vagal gastro-gastric relaxatory reflex. It is suggested that these two suppressive reflex mechanisms play an important role in regulation of gastric motor functions.

Publisher Summary This chapter focuses on ion transport in gastric mucosa. The muscosal surface of the stomach has a large number of openings, which are the gastric pits that produce the gastric secretion. The physiology of secretion can be roughly divided into two parts: one concerned with the basic mechanism by which the cells elaborate the secretion and the second with the control mechanisms. Gastric secretion is controlled by both hormonal and reflex mechanisms. The taste or smell of food can cause the stomach to secrete under conditions where the food does not come in contact with the mucosa. Food in contact with the stomach stimulates the liberation of the hormone gastrin from the antrum into the blood stream. The gastrin in the blood reaches the stomach and stimulates the formation of gastric juice. When the pH of the stomach contents reaches about 2, further liberation of gastrin is inhibited, the acid acting as a negative feedback to gastrin secretion. The chapter discusses the anatomy and physiology of the stomach. Active transport of H+ and Cl− is also analyzed in the chapter.

The effect of intravenous infusion of gastrin II on gastric and colonic motor activity was studied in 12 patients; gastric acid output was also measured. Administration of gastrin at near-maximal dose levels stimulates the motor activity of the antrum but has no measurable effect on the activity of the proximal colon, sigmoid, or rectum. The results suggest that gastrin plays a part in the regulation of gastric motility but that it is not a mediator of the gastro-colic reflex.

Numerous investigators have reported a delay in gastric evacuation as a result of placing acid, fat, gastric juice, etc., in the duodenum or other parts of the small intestine. The effect has generally been attributed to a reflex (the “Hirsch v. Mering reflex”) causing tonic contraction of the pyloric sphincter. However, two studies record inhibition of contractions of the pars pylorica following the introduction of acid1 or fat2 into the duodenum. Apparently both investigations were made upon the empty stomach, though Edelmann2 observed inhibition of gastric contractions during secretion of gastric juice. There are no data in either report to prove that the phenomenon occurs in the full stomach or has any bearing on the mechanism of gastric evacuation.We studied the effect of placing various substances in the duodenum while recording graphically the tone changes in the pyloric sphincter by means of the pressure tonometer,3 and the contractions of the pars pylorica by means of a balloon placed in the pylo...

The walls of the normal fasting stomach are maintained in coaptation by a state of tonus of its muscular coats, with recurrent periods of superimposed peristaltic activity. With the first taste of food there follows an immediate relaxation of gastric tonus with usually a fairly complete inhibition of peristalsis, resulting in a widening of the gastric lumen to accommodate the expected food injesta. This is the normal gastric feeding reflex (fig. 1). In the presence of various types of extragastric pathologic change, usually intra-abdominal or pelvic, this normal feeding reflex is distorted. Instead of relaxation there is an immediate increase in tone, with or without superimposed peristalsis. The degree of distortion roughly parallels the intensity of the sensory or psychic stimuli (fig. 2 A and B ) and is not influenced by the degree of acidity of the gastric secretions (table 1). These distortions of the normal gastric feeding reflex are