SCIENTIFIC PAPERS

Alkaline Reflux Gastritis

A Study in Forty Postoperative Duodenal Ulcer Patients

Romeo S. Berardi, MD, Des Moines, Iowa

Dawood Siroospour, MD, Des Moines, Iowa

Raul Ruiz, MD, Des Moines, Iowa

William Carnes, MD, Des Moines, Iowa

K. A. Devaiah, MD, Des Moines, Iowa

Carl Peterson, MD, Des Moines, Iowa

Wllliam E. Becknell, Jr, MD, Des Moines, Iowa

Jose Ollvencla, MD, Des Moines, Iowa

In 1947, Lambling and Gosset [I] presented clinical as well as experimental evidence indicating that re- flux of duodenopancreaticobiliary alkaline secretions into the stomach could produce gastritis. Since that time, alkaline reflux gastritis has gradually been es- tablished and accepted as a distinct clinical post- gastrectomy syndrome. What still remains unclear is the precise pathogenesis of this entity.

It is, nevertheless, generally accepted that alkaline reflux gastritis is more commonly seen in patients who have undergone Billroth II gastric resection than those with Billroth I or pyloroplasty with or without a vagotomy for the treatment of duodenal or gastric ulcer disease. What remains to be determined is the incidence of patients with symptomatic postopera- tive reflux gastritis; why many postoperative patients with gastroscopic and histologic evidence of gastritis remain asymptomatic while relatively few go on to have symptoms; and whether symptoms of postop- erative reflux gastritis are solely caused by the action of duodenal contents on the gastric mucosa or whether associated functional or organic distur- bances of the gastric remnant and/or newly formed gastrointestinal stoma play an important causative role in rendering the patient symptomatic.

From the Surgical Service, Veterans Administration Hospital, Des Moines, Iowa.

Reprint requests should be addressed to Romeo S. Berardi. MD. Surgical Service, Veterans Administration Hospital. Des Moines. Iowa 50310.

Since our experience, as well as that of others [2], has demonstrated that many asymptomatic post- operative patients with Billroth II gastric resection for duodenal ulcer disease have gastroscopic as well as histologic evidence of gastritis, we were prompted to undertake this prospective study.

Material and Methods

The first forty patients consenting to the protocol were entered into the study. All patients in the study were part of an ongoing follow-up program for surgically treated duodenal ulcer patients.

Studies obtained on these patients included: hemoglobin and hematocrit determinations; 12 hour gastric analysis for volume, appearance, bile pH, blood, free HCl, and so- dium concentration; upper gastrointestinal barium study; gastroscopy with biopsy and photography; and histologic examination of gastric biopsy specimens.

Gastroscopy was performed with a fiberoptic flexible gastroscope. Endoscopic appearance of the gastric mucosa and stoma as well as biliary reflux was noted. An average of four gastric biopsies were made in each patient from areas believed to represent gastritis endoscopically. In patients who did not demonstrate obvious gastritis, biopsies were obtained from the gastric side of the peri- stoma1 area. All specimens were examined by two pathol- ogists using the classification advocated by Whitehead, Truelove, and Gear [3]. This classification is essentially based on establishing four biopsy features: (1) the mucosal type; (2) the grade of chronic gastritis; (3) the activity of gastritis; and (4) the presence and type of metaplasia.

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Alkaline Reflux Gastritis

Results

The average age for this all male veteran popula- tion was 57.7 years (range, 41 to 80 years). Thirty- three patients (82.5 per cent) had vagotomy and distal antrectomy with an antecolic Polya gastroje- junostomy; four patients (10 per cent) had vagot- omy-pyloroplasty; three patients (7.5 per cent) had vagotomy-gastroenterostomy with an antecolic Polya anastomosis.

The average length of time from operation to the study period was 6.5 years (range, 2 to 18 years). Thirty-two patients (80 per cent) were asymptomatic and eight patients (20 per cent) were symptomatic. Symptoms consisted of occasional mild postprandial epigastric pain in seven patients and early prandial satiety in one patient. Three of the seven patients with epigastric pain were known alcoholics.

The average hemoglobin concentration was 14.3 gm/lOO ml. Only one patient in the study was found to be anemic, having a hemoglobin of 7 gm/lOO ml. The precise cause of this anemia was never deter2 mined. The average weight was 164 pounds (range, 105 to 252 pounds). The average height was 5 feet 8 inches (range, 5 feet 4 inches to 6 feet 2 inches). Only one patient was considered underweight for his height and general body frame.

Gastric Analysis. The 12 hour overnight gastric analysis revealed an average volume of 568.3 ml (range, 100 to 1,150 ml). The appearance of the gas- tric aspirate was a varied green color in all with the exception of five specimens having a brownish color and one being colorless. However, nine of the green specimens were negative for bile. All brownish specimens as well as the colorless one were negative for bile with the exception of one. The pH of the gastric specimens ranged from 1 to 7 (average, 5.8). Only five specimens had a pH of less than 4 and all of these had free HCl which averaged 19 mEq/l (range, 11.25 to 28 mEq/l). Four of the specimens with free HCl were green in appearance. All gastric specimens were positive for occult blood. Sodium concentrations averaged 67.23 mEq/l (range, 11.5 to 290 mEq/l). Only two patients had a sodium con- centration of less than 15 mEq/l.

Upper Gastrointestinal Barium Study. Upper gastrointestinal barium study was considered normal in thirty-four patients (85 per cent) and abnormal in six (15 per cent). Abnormal findings consisted of prominent rugal folds near the gastrojejunostomy stoma in five patients and a suspected marginal ulcer in one patient. In one study, the rugal folds near the peristomal area were described as being polypoid. Normal gastric emptying consistent with a postop-

erative stomach was noted in all studies. No study demonstrating delayed emptying was noted.

Of the five patients having prominent rugal folds radiologically, normal findings were noted endo- scopically and histologically in two. In the three pa- tients also having endoscopically prominent rugal folds, the peristomal gastric mucosa was hyperemic and edematous. Histologic examination of mucosal biopsies in these three patients revealed evidence of active mild to moderate atrophic gastritis. Of the six patients having abnormal radiologic studies, four were symptomatic and two were asymptomatic.

Gastroscopy. Gastroscopy revealed peristomal gastric mucosal hyperemia in sixteen patients; two patients had universal hyperemia of the gastric remnant and in one patient an associated grade II esophagitis was present. Peristomal hyperemia was associated with marked swelling in three patients, superficial erosions in one patient, and extremely friable mucosa in one patient. Superficial erosions thought to be secondary to the nasogastric tube were discounted. These usually were found in the upper gastric remnant and were generally surrounded by otherwise normal mucosa. The gastric side of the peristomal area was by far most commonly af- fected.

Gastroscopy did not reveal any significant gastric mucosal changes in twenty-two patients (55 per cent).

Seven of the eight symptomatic patients in this study demonstrated hyperemia of the gastric mucosa in the peristomal area. The average length of time from operation to the study period in these patients was 6.7 years (range, 2 to 15 years). Reflux of bile was noted during gastroscopic examination in all patients with the exception of two, both of whom had vagot- omy-pyloroplasty.

Histologic Examination. Histologic examination of the gastric mucosal biopsies revealed an essentially normal mucosa (Figure 1) in three patients (7.5 per cent), all of whom had normal gastroscopic findings. Biliary reflux, however, was noted in all three pa- tients. Active atrophic gastritis (Figure 2) was found in three patients, only one of whom was symptomatic, complaining of heartburn. All other specimens re- vealed evidence of either quiescent superficial (Fig- ure 3) or atrophic gastritis (Figure 4). Two specimens revealed epithelial metaplasia in the form of mucosal intestinalization. (Figure, 5.)

Other Observations. Of the five patients who had free HCl in the 12 hour overnight gastric analysis, two had normal gastroscopic findings and three had peristomal hyperemia. Biliary reflux was noted in all five patients. Histologic examination of the mucosal

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Berardi et al

Figure 1. Photomicrograph showing essentially normal Figure 2. Photomicrograph showing superficial erosion in surface gastric mucosa. ( Original magnification X 200; an active atrophic gastric mucosa. (Original magnification reduced 50 per cent. ) X 40; reduced 50 per cent. )

Figure 3. Photomicrograph showing quiescent superficial atrophic gastritis. ( Original magnification X 200; reduced 50 per cent. )

Figure 4. Photomicrograph showing quiescent atrophic gastritis. (Original magnification X 100; reduced 50 per cent. )

Figure 5. Photomkrograap showing typkai intestinaiization of gastric mucosa. (Original magnification X.20; reduced 50 per cent. )

Figure 6. Photomicrograph showing moderate edema of gastric mucosa ( Original magnificatkn X 40; reduced 50 per cent. )

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Alkaline Reflux Gastritis

biopsies obtained from these patients revealed nor- mal gastric mucosa in two, active atrophic gastritis in one, and quiescent superficial gastritis in two pa- tients. A histologically normal mucosa was associated with a gastroscopically hyperemic peristomal gastric mucosa in one patient.

Of the twenty-two patients having essentially normal gastroscopic findings, three had histologically normal mucosa; the remaining nineteen without exception had either quiescent superficial or atrophic gastritis with a mild to moderate chronic inflamma- tory response in the lamina propria consisting prin- cipally of lymphocytes, some plasma cells, and eo- sinophils. In one specimen edema was noted to be present. (Figure 6.)

All patients having a sodium concentration in the gastric aspirate greater than 15 mEq/l had some de- gree of gastritis, either active or quiescent. The two patients whose sodium concentrations were less than 15 mEq/l had normal gastric mucosa histologically as well as gastroscopically even though biliary reflux was noted gastroscopically.

Comments

Most authors would agree with Bushkin et al [4] that to establish the diagnosis of postoperative al- kaline reflux gastritis differentiation from other postgastrectomy states must be made on the basis of the type of operation the patient has had, the time sequence and variety of symptoms, the gastric acid studies, the roentgenographic and endoscopic stud- ies, and the histopathologic evaluation of mucosal biopsies.

Van Heerden et al [5] described a symptom com- plex suggesting the diagnosis of postoperative alka- line reflux gastritis, consisting of epigastric pain, aggravated by eating, alkali, or milk products, usually associated with anemia and weight loss.

The importance that each investigatory step has in establishing the diagnosis of alkaline reflux gas- tritis is clearly shown by this study and cannot be overemphasized. Since the pathogenesis of postop- erative alkaline reflux gastritis has not been defini- tively established [4], it is imperative that all patients suspected of having this entity be subjected to com- plete investigatory procedures.

The majority of patients (80 per cent) in this study were asymptomatic. Those patients who were symptomatic had mild symptoms not at all charac- teristic of postoperative alkaline reflux gastritis. Although 55 per cent of the patients had essentially normal gastroscopic findings, only 7.5 per cent had normal gastric mucosa upon histologic examination,

the remaining specimens revealing some degree of either quiescent or active superficial or atrophic gastritis. These findings support the contention of Cronstedt et al [6] who believe that gastritis can only be diagnosed with certainty on a histologic basis. Mysen and Serck-Hanssen [7] found the accuracy of gastroscopic diagnosis when compared with histo- logic examination to be 66 per cent for superficial gastritis, more than 70 per cent for a normal mucosa, and more than 80 per cent for atrophic gastritis. They excluded minimal grade I gastritis from the com- parison, thereby obtaining a somewhat higher cor- relation than noted in this study.

The point to be emphasized, however, is that many patients operated on for chronic duodenal ulcer re- veal some form of gastritis on histologic examination. This finding agrees with that of other authors [B-10]. Whether this gastritis is newly formed or whether it represents simply postoperative progression of gas- tritis associated with chronic ulcer disease is not a settled question, but that duodenal ulcer disease may be associated with gastritis has been fairly well doc- umented [12-141. The exact role this gastritis plays in patients manifesting symptoms suggestive of postoperative alkaline reflux gastritis needs further clarification [15]. The degree of gastritis noted on histologic examination of biopsy specimens does not always correlate well with patients who are symp- tomatic or asymptomatic. The need for further in- vestigation and clarification of the etiopathogenesis of alkaline reflux gastritis to determine its clinical significance is clear.

The production of alkaline gastritis presupposes reflux of duodenal contents into the stomach. The mere presence of reflux, although apparently essen- tial for the production of gastritis, does not neces- sarily result in making the patient symptomatic. Reflux was noted in all but two patients in this study. Furthermore, the sodium concentrations obtained in the gastric aspirates are indicative of significant reflux of alkaline duodenal contents. Fiddian-Green et al [16] found that reflux was related to sodium concentrations in that any patient with a sodium concentration of less than 15 mEq/l did not have gastritis and all patients with a sodium concentration greater than 15 mEq/l had gastritis. This same rela- tionship was noted in this study. Another aspect of gastric aspirates was studied by Brooks, Wenger, and Hersh [17] who found a significant overgrowth of bacteria, predominantly a-hemolytic streptococcus and diptheroids. Associated with bacterial over- growth were unconjugated bile salts, which they thought might account for the severity of the gastritis seen in the eleven patients studied.

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Although roentgenographic studies of the upper gastrointestinal tract are generally of limited use in the diagnosis of alkaline reflux gastritis, they occa- sionally do prove significant [18,19]. Most of the abnormalities noted on upper gastrointestinal bari- um studies are found near the gastrointestinal anastomosis. Thorfinnson and Brow [19] pointed out that these abnormalities, generally consisting of en- larged rugal folds, tend to occur two or more years after surgery in contrast with stoma1 ulcerations which tend to occur within the first two years. All patients in this study having abnormal radiologic studies were at least two years postoperative. More recently, Davidson and Hersh [20] have suggested that inadequate gastric emptying may be a contrib- uting factor in some symptomatic patients with al- kaline reflux gastritis. It is worthy of note that in- adequate or delayed gastric emptying was not ob- served in any patient in this study.

We have been impressed with the few patients we have surgically treated for alkaline reflux gastritis. All five patients who had previous Billroth II gastric resection were found to have a significant functional or organic abnormality at or related to the gastroin- testinal anastomosis and associated with gastroscopic and histologic evidence of gastritis. These abnor- malities included a retrograde intussusception of the efferent loop, intermittent functional obstruction of the afferent loop, stiffness of the gastrojejunostomy stoma, and redundant afferent loop. It is interesting to note that all but two were treated by a Roux-en-Y anastomosis and rendered asymptomatic. Two pa- tients required complete revision of the stoma, but the newly formed anastomosis included Roux-en-Y diversion of duodenal contents. These two patients also achieved a good result.

The possible association between alkaline reflux gastritis and other causes of postgastrectomy syn- dromes has been pointed out by others [21,22]. The point to be made, however, is that in some cases the performance of Roux-en-Y diversion of duodenal contents from the stomach might appear to have corrected the principal cause of the patient’s symp- toms-namely, correction of the apparent cause of alkaline reflux gastritis-whereas in reality what might have been corrected was an associated ab- normality of the gastrojejunostomy which could have been the primary cause of the patient’s symptoms. We believe this association is more common than is

realized and that in some cases the patient’s symp- toms may have very little to do with the associated gastritis [23]. This may be one reason why some au- thors [17] have noted that the response to medical treatment is only fair at best and that subsequent

diversion procedures are frequently required. That Roux-en-Y diversion of duodenal contents from the stomach is effective in alkaline reflux gastritis has been amply shown [5,21,24-261.

Our study shows that gastritis in postoperative patients treated for chronic duodenal ulcer is quite common. However, the overwhelming majority of such patients remain asymptomatic. It is, therefore, quite clear that not only the cause of gastritis but also the precise role gastritis plays in symptomatic pa- tients suspected of having alkaline reflux gastritis needs further investigation and clarification [27].

Summary

A study to determine the incidence of alkaline re- flux gastritis in forty postoperative duodenal ulcer patients has been presented. Since the majority of patients had evidence of gastritis, the precise role that gastritis plays in the production of symptoms is discussed but needs further clarification. It is sug- gested that the presence of gastritis may only rep- resent an incidental or associated finding in many patients presenting with symptoms presumably characteristic of alkaline reflux gastritis.

References

1. Lambling A, Gosset JR: Le Reflux des Secretions Alcalines duodeno-pancreaticobiliaires en physiopathologie gastrique. Etude critique, clinique et experimentale de la theorie de Bolyreff. Arch Ma/ App Digestif 36: 533, 1947.

2. Lees F, Grandjean LC: The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch intern Med 101: 943, 1956.

3. Whitehead R, Truelove SC, Gear MWL: The histological diag- nosis of chronic gastritis in fiberoptic gastroscope biopsy specimens. J C/in Pafhol25: 1, 1972.

4. Bushkin FL, Wickbom G, Deford JW, Woodward ER: Postop- erative alkaline reflux gastritis. Surg Gynecol Obstet 136: 933, 1974.

5. Van Heerden JA, Priestley JT, Farrow GM, Phillips SF: Post- operative alkaline reflux gastritis. Am J Surg 116: 427, 1969.

6. Cronstedt JL, Simson IW: Correlation between gastroscopic and direct vision biopsy findings. Gastrointest Endosc 19: 174, 1973.

7. Mysen J, Serck-Hanssen A: The gastroscopic diagnosis of gastritis, with particular reference to mucosal reddening and mucus covering. ScandJ Gastroenterol9: 457, 1974.

6. Aukee S, Krohn K: Occurrence and progression of gastritis in patients operated on for peptic ulcer. ScendJ Gastroenterol 7: 541, 1972.

9. Nielsen JA, Thaysen EH, Olesen H, Nielsen AR: Fundal gastritis after Billroth II-type resection in patients with duodenal ulcer. Stand J Gastroenterol6: 337, 1922.

10. Cornet A, DeBesse B. Barbier J, El Hada A, Carnot FR. Henry- Biabaud ED: Gastritis et stomites apres gastrectomie pour ulcere. Depistage radiologique et endoscopique. Sem Hop Paris 50: 1551, 1974.

11. Siurala M, Lehtola J, lhamaki T: Atrophic gastritis and its se- quelae. Results of 19-23 years follow-up examinations. Stand J Gastroenterol9: 441, 1974.

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12. Siurala M. Salmi W: Long-term follow-up of subjects with su- perficial gastritis or a normal gastric mucosa. Scasnd J Gsstroenterol6: 459. 197 1.

13. Skinner JM. Heenam PJ. Whitehead R: Atrophic gastritis in gastrectomy specimens. Br J Surg 62: 23, 1975.

14. Valencia-Parparcen J, Romet H: Gastritis: a study of 1000 consecutive gastric biopsies. Am J Dig Dis 8: 798. 1963.

15. Palmer ED: The clinical significance of nonspecific gastritis. Am J Dig Dis 10: 93, 1965.

16. Fiddian-Green Ft. Ball PAJ. Russell RCG, Hobsley M: Pyloric reflux and gastritis in man. Br J Surg 60: 321, 1973.

17. Brooks WS, Wenger J. Hersh T: Bile reflux gastritis. Analysis of fasting and postprandial gastric aspirates. Am J Gas- troenterol64: 286, 1975.

18. Kim SK, Rogers LS, Heitzrnan RE: Reflux alkaline gastritis. Am J Roentgenol Radium Ther Nucl h&d 115: 27 1, 1972.

19. Thorfinnson PC, Brow JR: Reflux bile gastritis. J Can Assoc Radio1 25: 263, 1974.

20. Davidson ED, Hersh T: Bile reflux gastritis. Contribution of in-

adequate gastric emptying. Am J Surg 130: 514. 1975. 2 1. Bushkin FL, DeFord JW, Wickbon G. Woodward ER: A clinical

evaluation of postoperative alkaline reflux gastritis. Am Swg 41: 88, 1975.

22. Verme G, Croce G: Le gastriti del monocone. Minerva Gas- troenterol 19: 41, 1973.

23. Keighley MRB, Asquith P. Alexander-Williams J: Postoperative duodenogastric reflux: a cause of gastritis and symptoms. Gut 15: 336. 1974.

24. Scudamore HH, Eckstam EE, Fencil WJ, Jaramillo CA: Bile reflux gastritis. Am J Gastroenterol60: 9, 1973.

25. Joseph WL, Rivera RA. O’Kieffe DA, Geelhoed GW. McCune WS: Management of postoperative alkaline reflux gastritis, Ann Surg 177: 655. 1973.

26. Pyrtek LJ. Bartus SA: Reflux bile gastritis. Am J Surg 125: 408, 1973.

27. Whitehead R: Aetiology and significance of simple chronic gastritis, chapt 3, p 33. Major Problems in Pathology. London. WB Saunders, 1973.

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