Reoperative Abdominal Surgery
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Alkaline Reflux Gastritis
William R. Burden, MD, * Richard P. Hodges, MD, * Michael Hsu, MD, t and]. Patrick O'Leary, MD+
HISTORICAL BACKGROUND
The symptoms of bilious vomiting and epigastric pain have been associated with gastric surgery since the first successful procedures were performed on the stomach. These symptoms were reported by WoHler following a gastroenterostomy performed at the Allgemeines Krankenhaus in Vienna in 1881. 37 Four years later, Billroth, operating at the same institution, reported similar symptoms after a gastrectomy. 1 The relation to the presence of bile in the stomach was recognized, but initially, this was thought to help protect against recurrent ulcer formation. DaCosta, in 1925, stated that the reflux of bile "antagonizes any tendency towards recurrence of ulceration. "7 This assertion was later (1947) disproved when Lambling and Gosset demonstrated that reflux of alkaline duodenal contents into the stomach could produce diffuse gastritis." In 1948, Lees and Grundjean demonstrated inflammatory changes in 32 of 33 patients who had undergone a gastrectomy for the treatment of peptic ulcer disease. 20 They theorized that these changes were the result of reflux of jejunal contents into the gastric remnant. In 1948, the afferent loop syndrome was described by Mimpriss and Birt,23whose findings were later confirmed by Wells and Welboum.:" After the publication of these articles, it became fashionable to attribute all symptoms of bilious vomiting and epigastric pain to intermittent obstruction of the afferent loop. Toye and Alexander-Williams aspirated the contents of a functioning afferent loop and instilled them into the gastric pouch'" and found that the instillation of the loop contents, primarily bile and alkaline secretions, caused an exacerbation of the patient's symptoms, From the Department of Surgery, Louisiana State University Medical Center, New Orleans, Louisiana *Resident t Assistant Professor :f:Professor and Chairman
Surgical Clinics of North America-Vol. 71, No.1, February 1991
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whereas the instillation of an equal volume of saline did not have any effect. By demonstrating that the symptoms were not secondary to obstruction of the afferent loop, they laid the groundwork for the definition of a new postgastrectomy syndrome, alkaline reflux gastritis. In 1964, Lawson showed that the reflux of duodenal contents into the stomach produces extensive gastritis. 19 By 1968, Davenport had shown that these effects are attributable to the breakdown of the mucosa caused by bile salts." He later demonstrated that bile salts permit backdiffusion of hydrogen ions. His work with animal models was confirmed in humans by Ivey and coworkers.!" Black showed that a low pH facilitates the effect of bile salts on the mucosal barrier, and Skillman subsequently demonstrated that backdiffusion is facilitated by mucosal ischemia. In the early 1970s, Van Heerden coined the term "postgastrectomy alkaline reflux gastritis."
DIAGNOSIS Although alkaline reflux gastritis is associated with a constellation of specific symptoms, there has been a great deal of crossover between these symptoms and the symptoms of various others of the postgastrectomy syndromes. This in part accounts for the inability of researchers to produce uniformly good results in a consistent manner." It has been suggested that the true incidence of alkaline reflux gastritis ranges from 5% to 35% in patients who have had operations that obliterate the sphincteric functions of the pylorus. Other authors have estimated the incidence at 3% of gastrectomized patients. 28 Alkaline reflux gastritis can follow a multitude of surgical procedures, Most frequently, it is associated with a Billroth II gastric reconstruction. 32 However, it may also follow Billroth I gastroduodenostomy, simple gastrojejunostomy, or pyloroplasty." Uncommonly, alkaline reflux gastritis has been reported after cholecystectomy or ampullary sphincteroplasty without surgical alteration of the pyloric function. In these instances, the biliary and pancreatic secretions are thought to enter the duodenum continuously secondary to the lack of the gallbladder reservoir function or the absence of the ampullary sphincter. As excess duodenal contents become available for reflux into the stomach, alkaline reflux gastritis develops." Finally, alkaline reflux gastritis has been described in a small percentage of patients who had not had a gastric or biliary tract operation." These patients tend to have reduced pyloric pressure and abnormal sphincteric response to both endogenous and exogenous gastrointestinal stimulation. It should be noted that some well-informed gastrointestinal researchers in the field doubt the very existence of the syndrome. James C. Thompson, in his discussion of a paper on alkaline reflux gastritis, stated that the findings of gastritis are too nonspecific to be associated with an individual diagosis, and because the main symptoms are subjective, he doubted that a specific condition exists. Because of the complexity of the symptoms, a detailed and careful history has been considered mandatory for the diagnosis of alkaline reflux gastritis. A patient typically complains of continuous epigastric pain, nausea,
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and bilious vomiting. In some patients, the pain extends into the back. Approximately 10% of patients also have symptoms of early postprandial dumping. Other, less consistent, features include weight loss, which probably is related to anorexia or the fear of provoking vomiting, and iron deficiency anemia. Among the postgastrectomy syndromes, the symptoms of alkaline reflux gastritis are most commonly confused with those of chronic afferent loop syndrome (Table 1).31 Both conditions can produce abdominal pain, nausea, and vomiting. However, in alkaline reflux gastritis, the pain usually is persistent and burning and unrelieved by vomiting, whereas the pain of afferent loop syndrome typically is postprandial and colicky and often is relieved by vomiting. Although weight loss is common with both syndromes, significant anemia is rarely seen in patients with chronic afferent loop syndrome. Routine radiography, such as barium study, has commonly been performed but has rarely proved helpful in making the diagnosis of alkaline reflux gastritis. It has been useful in defining the postoperative anatomy and in excluding alternative causes of symptoms such as recurrent peptic ulcer disease, atrophic gastritis, gastric polyps, gastric cancer, and mechanical obstruction. Pyloric regurgitation tests using diluted barium suspension instilled through a duodenal tube have been advocated to study the extent of reflux" Although helpful, the test requires the presence of a tube through the pylorus that may actually encourage duodenogastric reflux, making the results difficult to interpret. More recently, radionuclide techniques of external scanning for the study of enterogastric reflux have been developed. The isotope used has been 99m-technetium-labeled HIDA. This test not only allows documentation but also provides quantitative analysis of the severity of enterogastric reflux. Using this test, Ritchie has obtained net bile reflux, from which an enterogastric reflux index can be calculated;" This index, along with gastric emptying time, has assisted surgeons in identifying patients who might benefit from a remedial operation.F' Table 1. Symptom Complex of Afferent Loop Syndrome (ALS) and Alkaline Reflux Gastritis (ARG) ALS
Pain Quality Timing Relation to vomiting Vomitus
Malnutrition Anemia
ARC
Upper abdominal; bursting, Upper abdominal; burning, crampy, crushing aching, boring After meals; peaks about 30 min Continuous; may be aggravated postcibal by meals Complete relief Little effect Postcibal, projectile; contains no Sporadic; can occur after meals, food, bitter dark, "slimy," less projectile; often contains bilious; has no odor food particles; may smell feculent Usual, severe Infrequent, mild Infrequent Frequent, microcytic
From O'Leary IP, Bluett M: Reoperation for alkaline reflux gastritis. In Fry DE (ed): Reoperative Surgery of the Abdomen. New York, Marcel Dekker, p 104, 1986; with permission.
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Gastric analysis often aids in the diagnosis of alkaline reflux gastritis. In symptomatic patients, hypochlorhydria or achlorhydria usually is present secondary to markedly reduced acid production by the parietal cell mass. Gastric pH characteristically remains at 6. a or above. In comparison, gastric pH seldom remains above 6. a throughout the day and night in patients who have had a vagotomy or in patients with a gastric ulcer.:" In addition, if large amounts of hydrochloric acid are present, a marginal ulcer should be suspected. Endoscopic examination with multiple mucosal biopsies has proved to be the most important step in confirming the diagnosis of alkaline reflux gastritis. Bile pooling and reflux can be observed directly by endoscopy. Grossly, the gastric mucosa has been characterized by marked hyperemia, especially near the stoma or pyloroplasty. Hyperemia with bile staining of the esophagus may also be present. Superficial gastritis and ulcerations usually have involved the entire gastric remnant, but the process is most profound along the lesser curvature of the stomach. Because of the friability of the mucosa, occasional mucosal bleeding has been seen. It should be noted that simple perianastomotic inflammation has not been sufficient to establish a diagnosis of alkaline reflux gastritis. For this reason, multiple biopsies of the entire gastric pouch are necessary to document pangastric involvement. Histologically, several characteristic changes may be seen. A notable decrease or absence of both parietal and chief cells has been described in association with an increased number of mucin-secreting cells. The superficial mucosa characteristically shows ulcerations and atrophic changes, whereas the deep mucosa within the gastric pits remains relatively normal. An accumulation of chronic inflammatory cells, predominantly lymphocytes, occurs in the submucosa of the gastric glands. The glands are greatly distorted, dilated, and elongated, taking on a corkscrew appearance. 39 Finally, intestinal metaplasia, with formation of small-intestinal villi, has been described. In addition, there are substantial vascular changes. These include minimal infiltration of inflammatory cells and other histologic changes similar to those seen with the histamine-mediated response to injury. The mean mucosal mast cell count is decreased. If the alkaline secretions are diverted, the mast cell count is significantly increased, and the histologic picture changes to resemble that of type B chronic gastritis. These findings have been explained by the increased degranulation of the mast cell population in patients with alkaline reflux gastritis. 21 Intragastric infusion of alkaline solution as a provocative test would appear to have positive results both in identifying patients with alkaline reflux gastritis and in predicting a favorable surgical outcome. The test consists of the instillation at different times of a standardized volume of saline solution, a.IN hydrochloric acid, a.IN sodium hydroxide solution, as well as the patient's own gastric aspirates. This instillation is performed in a random blinded fashion through a nasogastric tube." A positive response is defined as reproduction of the patient's usual pain with or without vomiting by the alkali solution or the patient's own gastric contents. The patient should not have symptoms with the injection of saline or acid
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solutions. In one series, 4-year follow-up showed a predictive accuracy of 75% to 85% for a positive response to the test and an established benefit from operative intervention, and a negative test with a lack of benefit from the operation.:" These data appear quite promising, although additional clinical testing and long-term follow-up will be needed to establish the usefulness of the test.
PATHOPHYSIOLOGY
The exact mechanism for the production of alkaline reflux gastritis remains unknown. Attempts to elucidate the pathophysiology have led investigators to concentrate their efforts on the motility disorders known to be present and the cytotoxic effects of bile and pancreatic enzymes on the susceptible mucosa. The observations that bilious regurgitation occurs in patients without symptomatic gastritis and that gastric ulcers heal in the face of continued alkaline reflux suggest that there are host defense factors that account for the variability of symptoms after gastric surgery. These factors may include mucosal atrophy, alterations in mucosal blood flow, surface coating properties of gastric mucin, backdiffusion of hydrogen ions, direct effects of bile salts, and properties of gastric emptying. The sine qua non of alkaline reflux gastritis is reflux of intestinal contents into the gastric remnant as a result of ablation, destruction, or bypass of the pyloric sphincter. The motility patterns in the distal antrum, pylorus, and duodenum are complex. Rees and his colleagues studied normal persons and described high-pressure waves of low amplitude that progressed from the antrum to the duodenum. 27 There were isolated bursts of duodenal activity and retrograde peristalsis even in these normal individuals. The pattern of gastric emptying was normal. They concluded that duodenal reflux was a normal phenomenon and of no pathologic significance if the overall rate of gastric emptying was normal. Sorgi and Keighley have demonstrated in patients with duodenal ulcer and in controls that enterogastric reflux is common under basal conditions, but the refluxed material is rapidly cleared from the stomach;" They also found that duodenogastric reflux is often associated with gross abnormalities of gastric emptying. Furthermore, severe symptoms invariably occurred in their patients with reflux and delayed gastric emptying. The rate of gastric emptying and the contents of the enterogastric reflux would appear to have some pathologic effect on the development of alkaline reflux gastritis. Attempts to determine the agent responsible for the cytotoxic effects of gastritis have revealed no single factor that can account for all of the histopathologic changes. In early experiments, infusion of intestinal contents into gastric pouches of animals resulted in histologic gastritis. Davenport demonstrated that bile and bile salts disrupt the biochemical integrity of the gastric mucosa." In vitro studies using rabbit mucosa showed that topical bile salts increase the physical permeability of gastric mucosal membranes, as well as the induction of backdiffusion of hydrogen ions and the subsequent local release of histamine. The question of why bile reflux is harmful in some patients and in
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others produces no ill effects has led investigators to analyze the concentration and composition of the bile salts in the refluxate. Total bile acid concentrations are higher in patients with symptomatic enterogastric reflux than in asymptomatic patients. Harmon and associates showed a linear relation between the concentration of bile acids and the degree of mucosal damage in Heidenhain pouches created in the canine model. 13 Furthermore, Gadasz and Zuidema found that the gastric aspirate in patients with symptomatic alkaline reflux gastritis has a significantly higher concentration of deoxycholic acid than that from patients with asymptomatic bile reflux. 10 Subsequent in vitro studies showed that dihydroxy secondary bile salts, especially taurodeoxycholic acid, are most toxic to canine gastric mucosa. 3 Brooks and coworkers proposed that after gastric resection and vagotomy, patients have hypoacidity and gastric stasis, which permits the overgrowth of bacteria in the gastric pouch." Bacteria then deconjugate bile salts, producing the secondary bile acids, which are toxic to the gastric mucosa. The type of gastric microflora is influenced by the type of gastric procedure performed. 32 Escherichia coli is uncommon in the stomach except after a partial gastrectomy. Bacteroides fragilis, Bifidobacterium, Clostridium, and enterococci are capable of deconjugating and dehydroxylating bile salts. These strains of bacteria have been isolated with increased frequency after pyloroplasty or partial gastric resection. Because bacterial overgrowth is common in postgastrectomy patients, to date, no clear cause and effect relation has emerged between the type of procedure performed, the bacterial flora, and the symptoms. The relation of pancreatic juice to alkaline reflux gastritis has yet to be elucidated. Lawson demonstrated in vitro that bile and pancreatic juice are more damaging to gastric mucosa than is bile alone. 19 Other investigators have demonstrated that pancreatic enzymes, such as lysolecithin or phospholipase A2 , cause significant mucosal damage in vitro." Certain phospholipids, as well as bile salts, decrease the viscosity and elasticity of gastric mucus. However, careful clinical studies to assess the importance of the various constituents of duodenal fluids, except for bile salts, are lacking.
MEDICAL MANAGEMENT Medical management of patients with alkaline reflux gastritis has been of dubious value. Except for anecdotal claims of response, most often in patients with mild symptoms, no drug has been shown to be clearly effective in relieving symptoms. Nonetheless, a trial of medical therapy has often proved useful. Patients with acid hypersecretion or gastric stasis who have been misdiagnosed may respond to therapy addressed at their primary disease process. For the patient with emotional and psychiatric disturbance, the physician has been given time to assess more accurately the relation of the symptoms to the patient's personality before committing the patient to an operative procedure. 25 Antacids and H 2 antagonists have been advocated in the treatment of patients with alkaline reflux gastritis. There would appear to be little rationale for their use, as the majority of these patients are hypochlorhydric.
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Certain antacids, especially those containing aluminum hydroxide, bind bile salts and lysolecithin in vitro. This may account for the relief of symptoms with these agents in certain patients with alkaline reflux gastritis. Sucralfate in an acid medium becomes viscous and adheres to exposed proteins in the damaged mucosa. This substance has been postulated to form a protective barrier, allowing the injury to heal when protected from the hostile intraluminal milieu. Lacz and coworkers have shown normal binding of sucralfate in rats treated with cimetidine, suggesting that the drug exerts a cytoprotective role, even in a less acidic medium.F No controlled randomized studies are currently available that establish the efficacy of sucralfate in the treatment of alkaline reflux gastritis, but preliminary clinical experience indicates that it may relieve mild symptoms. No deleterious effects have been seen to date. Cholestyramine is a basic anionic exchange resin. It can be taken orally as a powder mixed with an appropriate fluid medium, although it has a somewhat disagreeable taste and a strong aftertaste. The drug was hypothesized to exert its effect by binding with bile salts in the gastric pouch, thus diminishing the concentration of bile salts available to interact with the gastric mucosa. Because the chemical reaction with the bile salts is nonreversible, the resin complex with the bile salts would pass through the gastrointestinal tract unabsorbed. This would diminish the bile salt pool and increase the turnover rate for bile salts. As the taurine supply of the body becomes exhausted, the majority of the bile salts become glycine conjugates. This would decrease the amount of taurine-conjugated secondary bile salts, thereby decreasing the concentration of one of the hypothesized culprits in gastric mucosal injury. Preliminary studies showed a benefit in patients with mild symptoms. These studies can be criticized, however, as it is impossible to disguise the taste and odor of the active ingredient being tested. Therefore, the studies were performed in a nonrandomized and nonblinded fashion. Subsequent studies have not confirmed the beneficial effect seen in these early trials. Additionally, patient compliance has been poor because of the drug's less than aesthetic properties. Metoclopramide also has been tried in patients with alkaline reflux gastritis. In the intact stomach, this drug causes more rapid emptying by increasing the force of antral contractions. Preliminary trials showed a salutary effect in some patients; however, subsequent studies have not demonstrated any clear benefits. 12 Metoclopramide also increases the resting tone of the lower esophageal sphincter and may be used in the treatment of patients with alkaline reflux esophagitis. U rsodeoxycholic acid relieves mild symptoms of alkaline reflux gastritis, presumably by altering the bile salt composition of the refluxate to a less toxic form.:" The amounts of cholic, deoxycholic, chenodeoxycholic, and lithocholic acids were reduced by 25% to 50% during treatment. The concentration of ursodeoxycholic acid increased by 40%. Antibiotics have been given to patients with alkaline reflux gastritis in an attempt to treat the bacterial overgrowth postulated to increase the conversion of conjugated bile salts to their more unconjugated form. However, no clinical studies are available on the effects of altering the gastric flora in patients with alkaline reflux gastritis.
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If the patient's symptoms persist, the condition interferes with the usual lifestyle, and he or she is an acceptable candidate for an abdominal procedure, the patient should be offered a revisional operation.
SURGICAL MANAGEMENT The criteria for surgical intervention are: (1) symptoms consistent with alkaline reflux gastritis that interfere with the patient's lifestyle; (2) symptoms that have failed to improve with medical management; (3) endoscopic evidence of bile and alkaline secretions within the gastric remnant; (4) histologic evidence of diffuse gastritis; and (5) evidence of hypochlorhydria. Some patients with the most severe symptoms may also have anemia. The goal of surgical management is the diversion of the duodenal contents away from the gastric remnant. A large number of different procedures have been proposed. Often, patients had more than one of the postgastrectomy syndromes, and the therapy was not appropriately tailored to address the patient's principal problem. In the early 1950s, Henle proposed to place an isolated, although perfused, section of jejunum between the distal stomach and the duodenum." This jejunum was placed in an isoperistaltic fashion as a primary operation to treat duodenal ulcer disease. The long-term results were disastrous, and the operation for that indication was abandoned. Subsequently, Henle described the same procedure to treat patients with the postgastrectomy syndromes. 14 In these conditions, the results were much better. Several investigators, including Poth;" Drapanas.!" and Buskin": 5 and their coworkers, demonstrated that symptoms of alkaline reflux gastritis were diminished in patients in whom an isoperistaltic segment of jejunum was positioned between the distal gastric pouch and the first portion of the duodenum. At least two of these authors compared and contrasted the results of the Roux-en-Y gastrojejunostomy with the Henle interposition. Relief of symptoms was significantly more likely in patients treated with the Roux-en-Y gastrojejunostomy. As data have accumulated, approximately 80% to 85% of patients have been found to have good to excellent relief of symptoms that had previously been ascribed to the alkaline reflux gastritis. Roux-en-Y diversion with the jejunojejunal anastomosis 45 to 60 em from the gastroenterostomy is now the most common remedial procedure for alkaline reflux gastritis. This operation diverts the duodenal secretions away from the gastric pouch, and the long jejunal limb effectively prevents reflux of these fluids into the stomach. Thus, the Roux-en-Y effectively meets the goals required for relief of symptoms. If a Roux-en-Y is to be performed, a complete vagotomy should either be a part of the procedure or have been performed previously. If such is not the- case, in effect the surgeon will be producing an Exalto-Mann-Williamson preparation. If a Roux limb of intestine is anastomosed to a part of the gastrointestinal tract that is producing hydrochloric acid, an ulcer will be produced in the small intestine. If a loop gastrojejunostomy is performed, the incidence of a marginal ulcer, although not zero, is much less, perhaps because the bile
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and pancreatic juices secreted into the duodenal limb have some protective effect to prevent the marginal ulceration. By the same token, as noted in the earlier part of this text, these secretions can be deleterious to the mucosa of the stomach. The purpose of the operative procedure is to divert these secretions away from the gastric pouch. The use of 45 em (18 inches) as the minimal effective length for the Roux-en-Y limb first appeared in the literature in the early 1970s. The number apparently was chosen on the basis of clinical experience and without solid documentation that this length would produce the protection desired (ER Woodward, personal communication). Subsequently, both animal and human studies have shown that this dimension prevents reflux of duodenal contents to the site of the gastroenterostomy in almost all patients. In patients who have had a vagotomy and pyloroplasty, and in patients who have had a simple gastroenterostomy, an antrectomy should be performed. The elimination of both the neural and the hormonal phases of gastric acid secretion gives the maximum protection against the ulcerogenic effect of the Roux-en-Y gastrojejunostomy. For patients who have had a previous antrectomy and Billroth II anastomosis, the Roux-en-Y can be created simply by stapling across the afferent limb and moving the jejunojejunostomy caudally at least 45 ern. Some surgeons prefer to convert the Billroth II anastomosis to a Tanner 19, which is done by dividing the afferent limb approximately 10 to 20 em from the gastrojejunostomy and performing an end-to-side anastomosis between the distal end of the divided intestine and the side of the efferent limb close to the remaining gastrojejunostomy. This provides a small, circular route at the point where the stomach empties into the small intestine. The proximal end of the divided afferent loop is then spliced to the jejunum at least 45 em caudally from the gastrojejunostomy. The measurement should be taken from the loop of the Tanner 19 jejunojenostomy and not from the gastrojejunostomy. Although some surgeons feel that the Tanner 19 increases the storage capacity of the gastric pouch and facilitates gastric emptying, to date, no controlled, randomized studies have been performed to prove that this procedure has any greater efficacy in ameliorating postoperative symptoms than does the standard Roux-en-Y gastrojejunostomy conversion. The control of symptoms of alkaline reflux gastritis with the Roux-enY gastrojejunostomy has not come without certain costs. A number of patients complained of early satiety, halitosis, vomiting of food that had been eaten days previously, and a sensation of bloating that was associated with upper abdominal fullness. Some patients even described a succussion splash in their upper abdomen. Although the symptoms of alkaline reflux gastritis had been relieved, symptoms of gastric outlet obstruction were common. Radionuclide studies of gastric emptying demonstrated that in excess of 50% of patients showed a profound delay in gastric emptying after the Roux-en-Y procedure. At first, these patients were felt to have a mechanical problem at the gastrojejunostomy. Many of these patients underwent barium studies of the upper gastrointestinal tract and endoscopic procedures. Characteristically, the barium would appear not to empty from the
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stomach, especially if the patient remained supine. Gastroscopic examination commonly showed a healthy-appearing gastric mucosa and a widely patent outflow tract. The search for an explanation of this apparent dichotomy was taken to the research laboratory. A number of studies were performed in animals, in which radionuclide emptying studies were carried out. 15 Diminished gastric emptying was demonstrated in almost all animals. Myoelectric activity monitoring of the Roux-en-Y limb of jejunum showed a chaotic disorder of electrical activity, and no dominant aboral peristaltic waves could be demonstrated. With time, the electrical activity of the Roux limb improved, and gastric emptying times shortened. However, gastric emptying rarely returned to normal. Recent studies have demonstrated that the myoelectric activity of the stomach pouch also becomes deranged when a Roux-en-Y gastrojejunostomy has been performed." A standardized radionuclide-enriched meal empties poorly: 50% of the ingested isotope is present in the stomach more than 3 hours after the meal. If erythromycin is administered either parenterally or orally, gastric emptying improves and approaches normal levels, but the administration of metoclopramide does not improve gastric emptying. The effect of the erythromycin has been postulated to be through motilinmediated gastric contractility. It would appear that the erythromycin either acts as an agonist to the receptor site for motilin or interferes with motilin's degradation. An unanticipated beneficial effect of the delayed gastric emptying has been a substantial improvement in the symptoms associated with rapid emptying (both early and late dumping). A number of patients who have alkaline reflux gastritis also have dumping, and at times, dumping is the predominant complaint. When a Roux-en-Y gastrojejunostomy was performed, the symptoms of dumping abated. This effect has been directly proportional to the rate of gastric emptying. Subsequently, Miranda and associates reported a series of patients in whom the Roux-en-Y had been performed for a combination of symptoms of alkaline reflux gastritis and dumping. In 15 of 17 patients, the principal symptoms were totally alleviated. 24 Roux-en-Y gastrojejunostomy diversion is the most appropriate surgical procedure to use in patients with disabling symptoms of alkaline reflux gastritis. Although the success rate, when judged by the control of symptoms, has been good, the complications from the procedure are also substantial and should be discussed at length with the patient preoperatively. Recent studies would suggest that a well-conceived and executed operative procedure, coupled with detailed follow-up, the careful manipulation of diet, and the judicial use of agents that affect gastric emptying, can provide many of the patients a near-normal lifestyle.
SUMMARY
Alkaline reflux gastritis and the symptoms associated with alkaline reflux gastritis have been reported in the medical literature since shortly
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after Billroth successfully performed his first gastrectomy in the 1880s. The disease process is produced by, or at least is associated with, the reflux of alkaline secretions into the gastric remnant. Although it occurs after any procedure that ablates the pylorus including pyloroplasty, it would appear to be most common after a Billroth II gastrojejunostomy. How the alkaline secretions cause the gastritis is still controversial. Clearly, the most effective therapy is to reroute the secretions from the biliary tract, pancreas, and duodenum so that they will not reflux into the gastric remnant. This is most effectively accomplished by a Roux-en- Y gastrojejunostomy with the afferent limb measuring at least 18 inches (40 em), The surgeon and the patient should be aware that the construction of such a gastric outlet channel is associated with delayed gastric emptying. The etiology of this impaired emptying is also controversial. If the patient has symptoms of dumping (either early or late), these symptoms may also be abated using the Roux limb. At least 40% of patients will have gastric outlet obstruction. Supportive therapy is appropriate in the majority of these patients.
REFERENCES 1. Billroth T: Clinical Surgery (translated by CT Dent). London, New Sydenham Society, 1885 2. Boren CH, Way LW: Alkaline reflux gastritis: A reevaluation. Am J Surg 140:40, 1980 3. Brooks WS, Wenger J, Hersh T: Bile reflux gastritis. Am J Gastroenterol 64:286, 1975 4. Bushkin FL, Woodward ER: Postgastrectomy syndromes. In Major Problems in Clinical Surgery. Philadelphia, WB Saunders, 1976 5. Bushkin FL, Woodward ER, O'Leary JP: Experience with the jejunal loop interposition in the treatment of postgastrectomy disorders. Am Surg 43:101, 1977 6. Carlson RG, Courington KR, Hocking MP, et al: Erythromycin enhances gastric emptying in Roux-Y dogs with severe delayed gastric emptying. Presented at meeting of the Society of Surgeons for the Alimentary Tract. San Antonio, Texas, May 1990 7. DaCosta JB: Acute dilatation of the stomach. Braz Med 2:7, 1925 8. Davenport HW: Destruction of gastric mucosal barrier by detergent agents and urea. Gastroenterology 54:175, 1965 9. Davenport HW: Effect of lysolecithin, digitonin, and phospholipase A upon the dog's gastric mucosal barrier. Gastroenterology 59:505, 1970 10. Drapenas T, Bethea M: Reflux gastritis following gastric surgery. Ann Surg 179:618, 1974 11. Gadacz TR, Zuidema GD: Bile acid composition in patients with and without symptoms of postoperative reflux gastritis. Am J Surg 135:48, 1978 12. Goldstein F, Thornton JJ III, Abramson J, et al: Bile reflux gastritis and esophagitis in patients without prior gastric surgery with pilot study of the therapeutic effects of metaclopramide. Am J Gastroenterol 76:407, 1981 13. Harmon JW, Lewis CD, Gadacz T: Bile salt composition and concentration as determinants of canine gastric mucosal injury. Surgery 89:348, 1981 14. Henley FA: Gastrectomie avec replacement par Ie jejunum. Arch Mal App Digest 9:93, 1957 15. Hocking MP, Vogel SB, Falasca CA, et al: Delayed gastric emptying of liquids and solids following Roux-en- Y biliary diversion. Ann Surg 194:494, 1981 16. Ivey KJ, Den Beston I, Clifton JA: Effect of bile salts on ionic movement across the lumen gastric mucosa. Gastroenterology 59:683, 1970 17. Lacz JP, Drees DT, Brown RK: Sucralfate binding in cimetidine treated rats. Gastroenterology 84:1220, 1983 18. Lambling A, Gosset JR: The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch Intern Med 101:943, 1948 19. Lawson HH: Effects of duodenal contents in the gastric mucosa under experimental conditions. Lancet 1:469, 1964
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20. Lees R, Grandjean LC: The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch Intern Med 101:943, 1958 21. Mangham DC, Newbold KM: Mucosal mast cells in reflux gastritis and chronic (type B) gastritis. Histopathology 15:531, 1989 22. Menguy R, Chey W: Experiences with the treatment of alkaline reflux gastritis. Surgery 88:482, 1980 23. Mimpriss TW, Birt StJMC: Results of partial gastrectomy for peptic ulcer disease. Br J Surg 2:1095, 1948 24. Miranda R, Steffes B, O'Leary JP, et al: Surgical treatment of the postgastrectomy dumping syndrome. Am J Surg 139:40, 1980 25. Nath BJ, Warshaw AL: Alkaline reflux gastritis and esophagitis. Annu Rev Med 35:383, 1984 26. Poth EJ: The use of gastrointestinal reversal in surgical procedure. Am J Surg 118:893, 1969 27. Rees WPW, Malogelada JR: Simultaneous measurement of antroduodenal motility, gastric emptying, and duodenogastric reflux in man. Gut 20:963, 1979 28. Ritchie WP: Alkaline reflux gastritis: A critical reappraisal. Gut 25:975, 1984 29. Ritchie WP: Alkaline reflux gastritis: Late results on a controlled trial of diagnosis and treatment. Ann Surg 203:537, 1986 30. Rutledge PL, Warshaw AL: Diagnosis of symptomatic alkaline reflux gastritis and prediction of response to bile diversion operation by intragastric alkali provocation. Am J Surg 155:82, 1988 31. Sawyers JL: Management of postgastrectomy syndromes. Am J Surg 159:8, 1990 32. Sorgi M, Keighley MRB: Alkaline reflux gastritis: Assessment and therapy. Surg Annu 14:153, 1982 33. Stefaniwsky AB, Tint GS, Speck J, et al: Ursodeoxycholic acid reduces pain, nausea, and vomiting in patients with bile acid reflux gastritis. Gastroenterology 82:1188, 1982 34. Toye DKM, Alexander-Williams JA: Postgastrectomy bile vomiting. Lancet 1:524, 1965 35. Warshaw AL: Intragastric alkali infusion. Ann Surg 194:297, 1981 36. Wells CA, Welbourn RB: Postgastrectomy syndromes: A study in applied physiology. Br Med J 1:546, 1951 37. Wolfler A: Gastroenterostomie. Z Chir 8:705, 1881 38. Woodward ER, Hocking MP: Postgastrectomy syndromes. Surg Clin North Am 67:509 J 1987
Address reprint requests to J. Patrick O'Leary, MD Department of Surgery Louisiana State University Medical Center 1542 Tulane Avenue New Orleans, Louisiana 70112-2822
0039-6109/91 $0.00
+ .20
Alkaline Reflux Gastritis
William R. Burden, MD, * Richard P. Hodges, MD, * Michael Hsu, MD, t and]. Patrick O'Leary, MD+
HISTORICAL BACKGROUND
The symptoms of bilious vomiting and epigastric pain have been associated with gastric surgery since the first successful procedures were performed on the stomach. These symptoms were reported by WoHler following a gastroenterostomy performed at the Allgemeines Krankenhaus in Vienna in 1881. 37 Four years later, Billroth, operating at the same institution, reported similar symptoms after a gastrectomy. 1 The relation to the presence of bile in the stomach was recognized, but initially, this was thought to help protect against recurrent ulcer formation. DaCosta, in 1925, stated that the reflux of bile "antagonizes any tendency towards recurrence of ulceration. "7 This assertion was later (1947) disproved when Lambling and Gosset demonstrated that reflux of alkaline duodenal contents into the stomach could produce diffuse gastritis." In 1948, Lees and Grundjean demonstrated inflammatory changes in 32 of 33 patients who had undergone a gastrectomy for the treatment of peptic ulcer disease. 20 They theorized that these changes were the result of reflux of jejunal contents into the gastric remnant. In 1948, the afferent loop syndrome was described by Mimpriss and Birt,23whose findings were later confirmed by Wells and Welboum.:" After the publication of these articles, it became fashionable to attribute all symptoms of bilious vomiting and epigastric pain to intermittent obstruction of the afferent loop. Toye and Alexander-Williams aspirated the contents of a functioning afferent loop and instilled them into the gastric pouch'" and found that the instillation of the loop contents, primarily bile and alkaline secretions, caused an exacerbation of the patient's symptoms, From the Department of Surgery, Louisiana State University Medical Center, New Orleans, Louisiana *Resident t Assistant Professor :f:Professor and Chairman
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whereas the instillation of an equal volume of saline did not have any effect. By demonstrating that the symptoms were not secondary to obstruction of the afferent loop, they laid the groundwork for the definition of a new postgastrectomy syndrome, alkaline reflux gastritis. In 1964, Lawson showed that the reflux of duodenal contents into the stomach produces extensive gastritis. 19 By 1968, Davenport had shown that these effects are attributable to the breakdown of the mucosa caused by bile salts." He later demonstrated that bile salts permit backdiffusion of hydrogen ions. His work with animal models was confirmed in humans by Ivey and coworkers.!" Black showed that a low pH facilitates the effect of bile salts on the mucosal barrier, and Skillman subsequently demonstrated that backdiffusion is facilitated by mucosal ischemia. In the early 1970s, Van Heerden coined the term "postgastrectomy alkaline reflux gastritis."
DIAGNOSIS Although alkaline reflux gastritis is associated with a constellation of specific symptoms, there has been a great deal of crossover between these symptoms and the symptoms of various others of the postgastrectomy syndromes. This in part accounts for the inability of researchers to produce uniformly good results in a consistent manner." It has been suggested that the true incidence of alkaline reflux gastritis ranges from 5% to 35% in patients who have had operations that obliterate the sphincteric functions of the pylorus. Other authors have estimated the incidence at 3% of gastrectomized patients. 28 Alkaline reflux gastritis can follow a multitude of surgical procedures, Most frequently, it is associated with a Billroth II gastric reconstruction. 32 However, it may also follow Billroth I gastroduodenostomy, simple gastrojejunostomy, or pyloroplasty." Uncommonly, alkaline reflux gastritis has been reported after cholecystectomy or ampullary sphincteroplasty without surgical alteration of the pyloric function. In these instances, the biliary and pancreatic secretions are thought to enter the duodenum continuously secondary to the lack of the gallbladder reservoir function or the absence of the ampullary sphincter. As excess duodenal contents become available for reflux into the stomach, alkaline reflux gastritis develops." Finally, alkaline reflux gastritis has been described in a small percentage of patients who had not had a gastric or biliary tract operation." These patients tend to have reduced pyloric pressure and abnormal sphincteric response to both endogenous and exogenous gastrointestinal stimulation. It should be noted that some well-informed gastrointestinal researchers in the field doubt the very existence of the syndrome. James C. Thompson, in his discussion of a paper on alkaline reflux gastritis, stated that the findings of gastritis are too nonspecific to be associated with an individual diagosis, and because the main symptoms are subjective, he doubted that a specific condition exists. Because of the complexity of the symptoms, a detailed and careful history has been considered mandatory for the diagnosis of alkaline reflux gastritis. A patient typically complains of continuous epigastric pain, nausea,
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and bilious vomiting. In some patients, the pain extends into the back. Approximately 10% of patients also have symptoms of early postprandial dumping. Other, less consistent, features include weight loss, which probably is related to anorexia or the fear of provoking vomiting, and iron deficiency anemia. Among the postgastrectomy syndromes, the symptoms of alkaline reflux gastritis are most commonly confused with those of chronic afferent loop syndrome (Table 1).31 Both conditions can produce abdominal pain, nausea, and vomiting. However, in alkaline reflux gastritis, the pain usually is persistent and burning and unrelieved by vomiting, whereas the pain of afferent loop syndrome typically is postprandial and colicky and often is relieved by vomiting. Although weight loss is common with both syndromes, significant anemia is rarely seen in patients with chronic afferent loop syndrome. Routine radiography, such as barium study, has commonly been performed but has rarely proved helpful in making the diagnosis of alkaline reflux gastritis. It has been useful in defining the postoperative anatomy and in excluding alternative causes of symptoms such as recurrent peptic ulcer disease, atrophic gastritis, gastric polyps, gastric cancer, and mechanical obstruction. Pyloric regurgitation tests using diluted barium suspension instilled through a duodenal tube have been advocated to study the extent of reflux" Although helpful, the test requires the presence of a tube through the pylorus that may actually encourage duodenogastric reflux, making the results difficult to interpret. More recently, radionuclide techniques of external scanning for the study of enterogastric reflux have been developed. The isotope used has been 99m-technetium-labeled HIDA. This test not only allows documentation but also provides quantitative analysis of the severity of enterogastric reflux. Using this test, Ritchie has obtained net bile reflux, from which an enterogastric reflux index can be calculated;" This index, along with gastric emptying time, has assisted surgeons in identifying patients who might benefit from a remedial operation.F' Table 1. Symptom Complex of Afferent Loop Syndrome (ALS) and Alkaline Reflux Gastritis (ARG) ALS
Pain Quality Timing Relation to vomiting Vomitus
Malnutrition Anemia
ARC
Upper abdominal; bursting, Upper abdominal; burning, crampy, crushing aching, boring After meals; peaks about 30 min Continuous; may be aggravated postcibal by meals Complete relief Little effect Postcibal, projectile; contains no Sporadic; can occur after meals, food, bitter dark, "slimy," less projectile; often contains bilious; has no odor food particles; may smell feculent Usual, severe Infrequent, mild Infrequent Frequent, microcytic
From O'Leary IP, Bluett M: Reoperation for alkaline reflux gastritis. In Fry DE (ed): Reoperative Surgery of the Abdomen. New York, Marcel Dekker, p 104, 1986; with permission.
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Gastric analysis often aids in the diagnosis of alkaline reflux gastritis. In symptomatic patients, hypochlorhydria or achlorhydria usually is present secondary to markedly reduced acid production by the parietal cell mass. Gastric pH characteristically remains at 6. a or above. In comparison, gastric pH seldom remains above 6. a throughout the day and night in patients who have had a vagotomy or in patients with a gastric ulcer.:" In addition, if large amounts of hydrochloric acid are present, a marginal ulcer should be suspected. Endoscopic examination with multiple mucosal biopsies has proved to be the most important step in confirming the diagnosis of alkaline reflux gastritis. Bile pooling and reflux can be observed directly by endoscopy. Grossly, the gastric mucosa has been characterized by marked hyperemia, especially near the stoma or pyloroplasty. Hyperemia with bile staining of the esophagus may also be present. Superficial gastritis and ulcerations usually have involved the entire gastric remnant, but the process is most profound along the lesser curvature of the stomach. Because of the friability of the mucosa, occasional mucosal bleeding has been seen. It should be noted that simple perianastomotic inflammation has not been sufficient to establish a diagnosis of alkaline reflux gastritis. For this reason, multiple biopsies of the entire gastric pouch are necessary to document pangastric involvement. Histologically, several characteristic changes may be seen. A notable decrease or absence of both parietal and chief cells has been described in association with an increased number of mucin-secreting cells. The superficial mucosa characteristically shows ulcerations and atrophic changes, whereas the deep mucosa within the gastric pits remains relatively normal. An accumulation of chronic inflammatory cells, predominantly lymphocytes, occurs in the submucosa of the gastric glands. The glands are greatly distorted, dilated, and elongated, taking on a corkscrew appearance. 39 Finally, intestinal metaplasia, with formation of small-intestinal villi, has been described. In addition, there are substantial vascular changes. These include minimal infiltration of inflammatory cells and other histologic changes similar to those seen with the histamine-mediated response to injury. The mean mucosal mast cell count is decreased. If the alkaline secretions are diverted, the mast cell count is significantly increased, and the histologic picture changes to resemble that of type B chronic gastritis. These findings have been explained by the increased degranulation of the mast cell population in patients with alkaline reflux gastritis. 21 Intragastric infusion of alkaline solution as a provocative test would appear to have positive results both in identifying patients with alkaline reflux gastritis and in predicting a favorable surgical outcome. The test consists of the instillation at different times of a standardized volume of saline solution, a.IN hydrochloric acid, a.IN sodium hydroxide solution, as well as the patient's own gastric aspirates. This instillation is performed in a random blinded fashion through a nasogastric tube." A positive response is defined as reproduction of the patient's usual pain with or without vomiting by the alkali solution or the patient's own gastric contents. The patient should not have symptoms with the injection of saline or acid
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solutions. In one series, 4-year follow-up showed a predictive accuracy of 75% to 85% for a positive response to the test and an established benefit from operative intervention, and a negative test with a lack of benefit from the operation.:" These data appear quite promising, although additional clinical testing and long-term follow-up will be needed to establish the usefulness of the test.
PATHOPHYSIOLOGY
The exact mechanism for the production of alkaline reflux gastritis remains unknown. Attempts to elucidate the pathophysiology have led investigators to concentrate their efforts on the motility disorders known to be present and the cytotoxic effects of bile and pancreatic enzymes on the susceptible mucosa. The observations that bilious regurgitation occurs in patients without symptomatic gastritis and that gastric ulcers heal in the face of continued alkaline reflux suggest that there are host defense factors that account for the variability of symptoms after gastric surgery. These factors may include mucosal atrophy, alterations in mucosal blood flow, surface coating properties of gastric mucin, backdiffusion of hydrogen ions, direct effects of bile salts, and properties of gastric emptying. The sine qua non of alkaline reflux gastritis is reflux of intestinal contents into the gastric remnant as a result of ablation, destruction, or bypass of the pyloric sphincter. The motility patterns in the distal antrum, pylorus, and duodenum are complex. Rees and his colleagues studied normal persons and described high-pressure waves of low amplitude that progressed from the antrum to the duodenum. 27 There were isolated bursts of duodenal activity and retrograde peristalsis even in these normal individuals. The pattern of gastric emptying was normal. They concluded that duodenal reflux was a normal phenomenon and of no pathologic significance if the overall rate of gastric emptying was normal. Sorgi and Keighley have demonstrated in patients with duodenal ulcer and in controls that enterogastric reflux is common under basal conditions, but the refluxed material is rapidly cleared from the stomach;" They also found that duodenogastric reflux is often associated with gross abnormalities of gastric emptying. Furthermore, severe symptoms invariably occurred in their patients with reflux and delayed gastric emptying. The rate of gastric emptying and the contents of the enterogastric reflux would appear to have some pathologic effect on the development of alkaline reflux gastritis. Attempts to determine the agent responsible for the cytotoxic effects of gastritis have revealed no single factor that can account for all of the histopathologic changes. In early experiments, infusion of intestinal contents into gastric pouches of animals resulted in histologic gastritis. Davenport demonstrated that bile and bile salts disrupt the biochemical integrity of the gastric mucosa." In vitro studies using rabbit mucosa showed that topical bile salts increase the physical permeability of gastric mucosal membranes, as well as the induction of backdiffusion of hydrogen ions and the subsequent local release of histamine. The question of why bile reflux is harmful in some patients and in
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others produces no ill effects has led investigators to analyze the concentration and composition of the bile salts in the refluxate. Total bile acid concentrations are higher in patients with symptomatic enterogastric reflux than in asymptomatic patients. Harmon and associates showed a linear relation between the concentration of bile acids and the degree of mucosal damage in Heidenhain pouches created in the canine model. 13 Furthermore, Gadasz and Zuidema found that the gastric aspirate in patients with symptomatic alkaline reflux gastritis has a significantly higher concentration of deoxycholic acid than that from patients with asymptomatic bile reflux. 10 Subsequent in vitro studies showed that dihydroxy secondary bile salts, especially taurodeoxycholic acid, are most toxic to canine gastric mucosa. 3 Brooks and coworkers proposed that after gastric resection and vagotomy, patients have hypoacidity and gastric stasis, which permits the overgrowth of bacteria in the gastric pouch." Bacteria then deconjugate bile salts, producing the secondary bile acids, which are toxic to the gastric mucosa. The type of gastric microflora is influenced by the type of gastric procedure performed. 32 Escherichia coli is uncommon in the stomach except after a partial gastrectomy. Bacteroides fragilis, Bifidobacterium, Clostridium, and enterococci are capable of deconjugating and dehydroxylating bile salts. These strains of bacteria have been isolated with increased frequency after pyloroplasty or partial gastric resection. Because bacterial overgrowth is common in postgastrectomy patients, to date, no clear cause and effect relation has emerged between the type of procedure performed, the bacterial flora, and the symptoms. The relation of pancreatic juice to alkaline reflux gastritis has yet to be elucidated. Lawson demonstrated in vitro that bile and pancreatic juice are more damaging to gastric mucosa than is bile alone. 19 Other investigators have demonstrated that pancreatic enzymes, such as lysolecithin or phospholipase A2 , cause significant mucosal damage in vitro." Certain phospholipids, as well as bile salts, decrease the viscosity and elasticity of gastric mucus. However, careful clinical studies to assess the importance of the various constituents of duodenal fluids, except for bile salts, are lacking.
MEDICAL MANAGEMENT Medical management of patients with alkaline reflux gastritis has been of dubious value. Except for anecdotal claims of response, most often in patients with mild symptoms, no drug has been shown to be clearly effective in relieving symptoms. Nonetheless, a trial of medical therapy has often proved useful. Patients with acid hypersecretion or gastric stasis who have been misdiagnosed may respond to therapy addressed at their primary disease process. For the patient with emotional and psychiatric disturbance, the physician has been given time to assess more accurately the relation of the symptoms to the patient's personality before committing the patient to an operative procedure. 25 Antacids and H 2 antagonists have been advocated in the treatment of patients with alkaline reflux gastritis. There would appear to be little rationale for their use, as the majority of these patients are hypochlorhydric.
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Certain antacids, especially those containing aluminum hydroxide, bind bile salts and lysolecithin in vitro. This may account for the relief of symptoms with these agents in certain patients with alkaline reflux gastritis. Sucralfate in an acid medium becomes viscous and adheres to exposed proteins in the damaged mucosa. This substance has been postulated to form a protective barrier, allowing the injury to heal when protected from the hostile intraluminal milieu. Lacz and coworkers have shown normal binding of sucralfate in rats treated with cimetidine, suggesting that the drug exerts a cytoprotective role, even in a less acidic medium.F No controlled randomized studies are currently available that establish the efficacy of sucralfate in the treatment of alkaline reflux gastritis, but preliminary clinical experience indicates that it may relieve mild symptoms. No deleterious effects have been seen to date. Cholestyramine is a basic anionic exchange resin. It can be taken orally as a powder mixed with an appropriate fluid medium, although it has a somewhat disagreeable taste and a strong aftertaste. The drug was hypothesized to exert its effect by binding with bile salts in the gastric pouch, thus diminishing the concentration of bile salts available to interact with the gastric mucosa. Because the chemical reaction with the bile salts is nonreversible, the resin complex with the bile salts would pass through the gastrointestinal tract unabsorbed. This would diminish the bile salt pool and increase the turnover rate for bile salts. As the taurine supply of the body becomes exhausted, the majority of the bile salts become glycine conjugates. This would decrease the amount of taurine-conjugated secondary bile salts, thereby decreasing the concentration of one of the hypothesized culprits in gastric mucosal injury. Preliminary studies showed a benefit in patients with mild symptoms. These studies can be criticized, however, as it is impossible to disguise the taste and odor of the active ingredient being tested. Therefore, the studies were performed in a nonrandomized and nonblinded fashion. Subsequent studies have not confirmed the beneficial effect seen in these early trials. Additionally, patient compliance has been poor because of the drug's less than aesthetic properties. Metoclopramide also has been tried in patients with alkaline reflux gastritis. In the intact stomach, this drug causes more rapid emptying by increasing the force of antral contractions. Preliminary trials showed a salutary effect in some patients; however, subsequent studies have not demonstrated any clear benefits. 12 Metoclopramide also increases the resting tone of the lower esophageal sphincter and may be used in the treatment of patients with alkaline reflux esophagitis. U rsodeoxycholic acid relieves mild symptoms of alkaline reflux gastritis, presumably by altering the bile salt composition of the refluxate to a less toxic form.:" The amounts of cholic, deoxycholic, chenodeoxycholic, and lithocholic acids were reduced by 25% to 50% during treatment. The concentration of ursodeoxycholic acid increased by 40%. Antibiotics have been given to patients with alkaline reflux gastritis in an attempt to treat the bacterial overgrowth postulated to increase the conversion of conjugated bile salts to their more unconjugated form. However, no clinical studies are available on the effects of altering the gastric flora in patients with alkaline reflux gastritis.
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If the patient's symptoms persist, the condition interferes with the usual lifestyle, and he or she is an acceptable candidate for an abdominal procedure, the patient should be offered a revisional operation.
SURGICAL MANAGEMENT The criteria for surgical intervention are: (1) symptoms consistent with alkaline reflux gastritis that interfere with the patient's lifestyle; (2) symptoms that have failed to improve with medical management; (3) endoscopic evidence of bile and alkaline secretions within the gastric remnant; (4) histologic evidence of diffuse gastritis; and (5) evidence of hypochlorhydria. Some patients with the most severe symptoms may also have anemia. The goal of surgical management is the diversion of the duodenal contents away from the gastric remnant. A large number of different procedures have been proposed. Often, patients had more than one of the postgastrectomy syndromes, and the therapy was not appropriately tailored to address the patient's principal problem. In the early 1950s, Henle proposed to place an isolated, although perfused, section of jejunum between the distal stomach and the duodenum." This jejunum was placed in an isoperistaltic fashion as a primary operation to treat duodenal ulcer disease. The long-term results were disastrous, and the operation for that indication was abandoned. Subsequently, Henle described the same procedure to treat patients with the postgastrectomy syndromes. 14 In these conditions, the results were much better. Several investigators, including Poth;" Drapanas.!" and Buskin": 5 and their coworkers, demonstrated that symptoms of alkaline reflux gastritis were diminished in patients in whom an isoperistaltic segment of jejunum was positioned between the distal gastric pouch and the first portion of the duodenum. At least two of these authors compared and contrasted the results of the Roux-en-Y gastrojejunostomy with the Henle interposition. Relief of symptoms was significantly more likely in patients treated with the Roux-en-Y gastrojejunostomy. As data have accumulated, approximately 80% to 85% of patients have been found to have good to excellent relief of symptoms that had previously been ascribed to the alkaline reflux gastritis. Roux-en-Y diversion with the jejunojejunal anastomosis 45 to 60 em from the gastroenterostomy is now the most common remedial procedure for alkaline reflux gastritis. This operation diverts the duodenal secretions away from the gastric pouch, and the long jejunal limb effectively prevents reflux of these fluids into the stomach. Thus, the Roux-en-Y effectively meets the goals required for relief of symptoms. If a Roux-en-Y is to be performed, a complete vagotomy should either be a part of the procedure or have been performed previously. If such is not the- case, in effect the surgeon will be producing an Exalto-Mann-Williamson preparation. If a Roux limb of intestine is anastomosed to a part of the gastrointestinal tract that is producing hydrochloric acid, an ulcer will be produced in the small intestine. If a loop gastrojejunostomy is performed, the incidence of a marginal ulcer, although not zero, is much less, perhaps because the bile
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and pancreatic juices secreted into the duodenal limb have some protective effect to prevent the marginal ulceration. By the same token, as noted in the earlier part of this text, these secretions can be deleterious to the mucosa of the stomach. The purpose of the operative procedure is to divert these secretions away from the gastric pouch. The use of 45 em (18 inches) as the minimal effective length for the Roux-en-Y limb first appeared in the literature in the early 1970s. The number apparently was chosen on the basis of clinical experience and without solid documentation that this length would produce the protection desired (ER Woodward, personal communication). Subsequently, both animal and human studies have shown that this dimension prevents reflux of duodenal contents to the site of the gastroenterostomy in almost all patients. In patients who have had a vagotomy and pyloroplasty, and in patients who have had a simple gastroenterostomy, an antrectomy should be performed. The elimination of both the neural and the hormonal phases of gastric acid secretion gives the maximum protection against the ulcerogenic effect of the Roux-en-Y gastrojejunostomy. For patients who have had a previous antrectomy and Billroth II anastomosis, the Roux-en-Y can be created simply by stapling across the afferent limb and moving the jejunojejunostomy caudally at least 45 ern. Some surgeons prefer to convert the Billroth II anastomosis to a Tanner 19, which is done by dividing the afferent limb approximately 10 to 20 em from the gastrojejunostomy and performing an end-to-side anastomosis between the distal end of the divided intestine and the side of the efferent limb close to the remaining gastrojejunostomy. This provides a small, circular route at the point where the stomach empties into the small intestine. The proximal end of the divided afferent loop is then spliced to the jejunum at least 45 em caudally from the gastrojejunostomy. The measurement should be taken from the loop of the Tanner 19 jejunojenostomy and not from the gastrojejunostomy. Although some surgeons feel that the Tanner 19 increases the storage capacity of the gastric pouch and facilitates gastric emptying, to date, no controlled, randomized studies have been performed to prove that this procedure has any greater efficacy in ameliorating postoperative symptoms than does the standard Roux-en-Y gastrojejunostomy conversion. The control of symptoms of alkaline reflux gastritis with the Roux-enY gastrojejunostomy has not come without certain costs. A number of patients complained of early satiety, halitosis, vomiting of food that had been eaten days previously, and a sensation of bloating that was associated with upper abdominal fullness. Some patients even described a succussion splash in their upper abdomen. Although the symptoms of alkaline reflux gastritis had been relieved, symptoms of gastric outlet obstruction were common. Radionuclide studies of gastric emptying demonstrated that in excess of 50% of patients showed a profound delay in gastric emptying after the Roux-en-Y procedure. At first, these patients were felt to have a mechanical problem at the gastrojejunostomy. Many of these patients underwent barium studies of the upper gastrointestinal tract and endoscopic procedures. Characteristically, the barium would appear not to empty from the
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stomach, especially if the patient remained supine. Gastroscopic examination commonly showed a healthy-appearing gastric mucosa and a widely patent outflow tract. The search for an explanation of this apparent dichotomy was taken to the research laboratory. A number of studies were performed in animals, in which radionuclide emptying studies were carried out. 15 Diminished gastric emptying was demonstrated in almost all animals. Myoelectric activity monitoring of the Roux-en-Y limb of jejunum showed a chaotic disorder of electrical activity, and no dominant aboral peristaltic waves could be demonstrated. With time, the electrical activity of the Roux limb improved, and gastric emptying times shortened. However, gastric emptying rarely returned to normal. Recent studies have demonstrated that the myoelectric activity of the stomach pouch also becomes deranged when a Roux-en-Y gastrojejunostomy has been performed." A standardized radionuclide-enriched meal empties poorly: 50% of the ingested isotope is present in the stomach more than 3 hours after the meal. If erythromycin is administered either parenterally or orally, gastric emptying improves and approaches normal levels, but the administration of metoclopramide does not improve gastric emptying. The effect of the erythromycin has been postulated to be through motilinmediated gastric contractility. It would appear that the erythromycin either acts as an agonist to the receptor site for motilin or interferes with motilin's degradation. An unanticipated beneficial effect of the delayed gastric emptying has been a substantial improvement in the symptoms associated with rapid emptying (both early and late dumping). A number of patients who have alkaline reflux gastritis also have dumping, and at times, dumping is the predominant complaint. When a Roux-en-Y gastrojejunostomy was performed, the symptoms of dumping abated. This effect has been directly proportional to the rate of gastric emptying. Subsequently, Miranda and associates reported a series of patients in whom the Roux-en-Y had been performed for a combination of symptoms of alkaline reflux gastritis and dumping. In 15 of 17 patients, the principal symptoms were totally alleviated. 24 Roux-en-Y gastrojejunostomy diversion is the most appropriate surgical procedure to use in patients with disabling symptoms of alkaline reflux gastritis. Although the success rate, when judged by the control of symptoms, has been good, the complications from the procedure are also substantial and should be discussed at length with the patient preoperatively. Recent studies would suggest that a well-conceived and executed operative procedure, coupled with detailed follow-up, the careful manipulation of diet, and the judicial use of agents that affect gastric emptying, can provide many of the patients a near-normal lifestyle.
SUMMARY
Alkaline reflux gastritis and the symptoms associated with alkaline reflux gastritis have been reported in the medical literature since shortly
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after Billroth successfully performed his first gastrectomy in the 1880s. The disease process is produced by, or at least is associated with, the reflux of alkaline secretions into the gastric remnant. Although it occurs after any procedure that ablates the pylorus including pyloroplasty, it would appear to be most common after a Billroth II gastrojejunostomy. How the alkaline secretions cause the gastritis is still controversial. Clearly, the most effective therapy is to reroute the secretions from the biliary tract, pancreas, and duodenum so that they will not reflux into the gastric remnant. This is most effectively accomplished by a Roux-en- Y gastrojejunostomy with the afferent limb measuring at least 18 inches (40 em), The surgeon and the patient should be aware that the construction of such a gastric outlet channel is associated with delayed gastric emptying. The etiology of this impaired emptying is also controversial. If the patient has symptoms of dumping (either early or late), these symptoms may also be abated using the Roux limb. At least 40% of patients will have gastric outlet obstruction. Supportive therapy is appropriate in the majority of these patients.
REFERENCES 1. Billroth T: Clinical Surgery (translated by CT Dent). London, New Sydenham Society, 1885 2. Boren CH, Way LW: Alkaline reflux gastritis: A reevaluation. Am J Surg 140:40, 1980 3. Brooks WS, Wenger J, Hersh T: Bile reflux gastritis. Am J Gastroenterol 64:286, 1975 4. Bushkin FL, Woodward ER: Postgastrectomy syndromes. In Major Problems in Clinical Surgery. Philadelphia, WB Saunders, 1976 5. Bushkin FL, Woodward ER, O'Leary JP: Experience with the jejunal loop interposition in the treatment of postgastrectomy disorders. Am Surg 43:101, 1977 6. Carlson RG, Courington KR, Hocking MP, et al: Erythromycin enhances gastric emptying in Roux-Y dogs with severe delayed gastric emptying. Presented at meeting of the Society of Surgeons for the Alimentary Tract. San Antonio, Texas, May 1990 7. DaCosta JB: Acute dilatation of the stomach. Braz Med 2:7, 1925 8. Davenport HW: Destruction of gastric mucosal barrier by detergent agents and urea. Gastroenterology 54:175, 1965 9. Davenport HW: Effect of lysolecithin, digitonin, and phospholipase A upon the dog's gastric mucosal barrier. Gastroenterology 59:505, 1970 10. Drapenas T, Bethea M: Reflux gastritis following gastric surgery. Ann Surg 179:618, 1974 11. Gadacz TR, Zuidema GD: Bile acid composition in patients with and without symptoms of postoperative reflux gastritis. Am J Surg 135:48, 1978 12. Goldstein F, Thornton JJ III, Abramson J, et al: Bile reflux gastritis and esophagitis in patients without prior gastric surgery with pilot study of the therapeutic effects of metaclopramide. Am J Gastroenterol 76:407, 1981 13. Harmon JW, Lewis CD, Gadacz T: Bile salt composition and concentration as determinants of canine gastric mucosal injury. Surgery 89:348, 1981 14. Henley FA: Gastrectomie avec replacement par Ie jejunum. Arch Mal App Digest 9:93, 1957 15. Hocking MP, Vogel SB, Falasca CA, et al: Delayed gastric emptying of liquids and solids following Roux-en- Y biliary diversion. Ann Surg 194:494, 1981 16. Ivey KJ, Den Beston I, Clifton JA: Effect of bile salts on ionic movement across the lumen gastric mucosa. Gastroenterology 59:683, 1970 17. Lacz JP, Drees DT, Brown RK: Sucralfate binding in cimetidine treated rats. Gastroenterology 84:1220, 1983 18. Lambling A, Gosset JR: The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch Intern Med 101:943, 1948 19. Lawson HH: Effects of duodenal contents in the gastric mucosa under experimental conditions. Lancet 1:469, 1964
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20. Lees R, Grandjean LC: The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch Intern Med 101:943, 1958 21. Mangham DC, Newbold KM: Mucosal mast cells in reflux gastritis and chronic (type B) gastritis. Histopathology 15:531, 1989 22. Menguy R, Chey W: Experiences with the treatment of alkaline reflux gastritis. Surgery 88:482, 1980 23. Mimpriss TW, Birt StJMC: Results of partial gastrectomy for peptic ulcer disease. Br J Surg 2:1095, 1948 24. Miranda R, Steffes B, O'Leary JP, et al: Surgical treatment of the postgastrectomy dumping syndrome. Am J Surg 139:40, 1980 25. Nath BJ, Warshaw AL: Alkaline reflux gastritis and esophagitis. Annu Rev Med 35:383, 1984 26. Poth EJ: The use of gastrointestinal reversal in surgical procedure. Am J Surg 118:893, 1969 27. Rees WPW, Malogelada JR: Simultaneous measurement of antroduodenal motility, gastric emptying, and duodenogastric reflux in man. Gut 20:963, 1979 28. Ritchie WP: Alkaline reflux gastritis: A critical reappraisal. Gut 25:975, 1984 29. Ritchie WP: Alkaline reflux gastritis: Late results on a controlled trial of diagnosis and treatment. Ann Surg 203:537, 1986 30. Rutledge PL, Warshaw AL: Diagnosis of symptomatic alkaline reflux gastritis and prediction of response to bile diversion operation by intragastric alkali provocation. Am J Surg 155:82, 1988 31. Sawyers JL: Management of postgastrectomy syndromes. Am J Surg 159:8, 1990 32. Sorgi M, Keighley MRB: Alkaline reflux gastritis: Assessment and therapy. Surg Annu 14:153, 1982 33. Stefaniwsky AB, Tint GS, Speck J, et al: Ursodeoxycholic acid reduces pain, nausea, and vomiting in patients with bile acid reflux gastritis. Gastroenterology 82:1188, 1982 34. Toye DKM, Alexander-Williams JA: Postgastrectomy bile vomiting. Lancet 1:524, 1965 35. Warshaw AL: Intragastric alkali infusion. Ann Surg 194:297, 1981 36. Wells CA, Welbourn RB: Postgastrectomy syndromes: A study in applied physiology. Br Med J 1:546, 1951 37. Wolfler A: Gastroenterostomie. Z Chir 8:705, 1881 38. Woodward ER, Hocking MP: Postgastrectomy syndromes. Surg Clin North Am 67:509 J 1987
Address reprint requests to J. Patrick O'Leary, MD Department of Surgery Louisiana State University Medical Center 1542 Tulane Avenue New Orleans, Louisiana 70112-2822
