ANNALS Vol. 188

OF SURGERY

October 1978

No.

4

Effect of Selective Proximal Vagotomy and Truncal Vagotomy on Gastric Acid and Serum Gastrin Responses to a Meal in Duodenal Ulcer Patients JAMES C. THOMPSON, M.D., WEBSTER S. LOWDER, M.D., J. TOM PEURIFOY, M.D., JANUSZ S. SWIERCZEK, M.D.,* PHILLIP L. RAYFORD, PH.D. To assess the effectiveness of selective proximal vagotomy (SPV) in reducing the acid response to food, we have compared pre- and postoperative gastric acid and serum gastrin responses to a meal in 11 duodenal ulcer patients with intractable pain treated by SPV, with those of seven ulcer patients with gastric outlet obstruction treated by truncal vagotomy and drainage (TV + D). Acid secretion was measured by an intragastric titration method which measures acid response to food within the stomach (5% amino acid meal) adjusted to various pH levels (5.5, 2.5, and 1.5). Studies were performed before and two to six weeks after operation. The preoperative intragastric acid output (IGAO) was about 50% of maximal acid response to Histalog. The mean preoperative IGAO at pH 5.5 for 11 SPV patients was 17.4 ± 3.1 mEq/hour; this was decreased by 72% to 4.3 ± 1.1 mEq/hour after operation.' The mean IGAO at pH 5.5 in nine patients treated by TV + D was 21.6 ± 3.4 mEq/hour; this was decreased by 67% to 7.3 ± 2.1 mEq/hour. Gastrin levels were significantly higher in postop than in preop SPV patients even though pH values were constant. Gastrin levels were higher in postop TV + D patients than in postop SPV patients. This study demonstrates that acid reduction achieved by SPV is reliable and at least comparable with that achieved by truncal vagotomy. Postoperative elevation of gastrin in the SPV patients suggests that the vagus may release Presented at the Annual Meeting of the American Surgical Association, April 26-28, 1978, Dallas, Texas. Address correspondence: James C. Thompson, M.D., Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77550. * Visiting Scientist. Parent Institution: Institute of Physiology, Medical Academy, Karkow, Poland. Supported by grants from the National Institutes of Health (AM 15241) and General Clinical Research Centers Branch, DHEW Grant (RR 00073), and by a grant from the John A. Hartford Foundation, Inc.

From the Department of Surgery, The University of Texas Medical Branch, Galveston, Texas

a humoral inhibitor of gastrin release from the gastric fundus; there may also be a further direct vagal inhibitor of antral gastrin release.

TN THE ELECTIVE surgical treatment of duodenal 1 ulcer, the procedure of selective vagal denervation of the gastric fundus (which we will refer to as selective proximal vagotomy) approaches the theoretical ideal, in that it appears to be an effective treatment for the ulcer with little risk of mortality or serious complications. 9131521 The procedure offers the promise of curtailing acid secretion without the need for resection or drainage. Compared with other acid-reducing operations, selective proximal vagotomy appears to have distinct advantages, especially in the low risk of mortality, as well as in the near elimination of postoperative dumping and diarrhea.29 The questionable aspect of the procedure is whether acid secretory levels can reliably be reduced to the point that ulcers will remain healed. There are occasional reports of high rates of ulcer recurrence18 and high incidences (8090%) of positive Hollander tests. 12 We have recently compared acid and endocrine responses to an amino acid meal in normal duodenal ulcer subjects.30 The technique appears to offer an excellent means of reproducibly evaluating secretory

0003-4932/78/1000/0431 $00.85 X) J. B. Lippincott Company

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and endocrine responses to a nearly physiologic stimulus. In the present study, we have compared the gastric acid and serum gastrin responses to such a meal, before and after operation, in duodenal ulcer patients treated by selective proximal vagotomy with those of patients treated by truncal vagotomy and gastroenterostomy. Studies on the relationship of the vagus to antral gastrin have suggested that the vagus may suppress, as well as stimulate, gastrin release.2 3'22 The present studies have allowed us to study further the vagal control of gastrin release. The results suggest that the vagus may inhibit gastrin release by more than one route.

Materials and Methods We have done a prospective study of 20 patients with duodenal ulcer disease who were admitted or transferred to the Surgical Service of The University of Texas Medical Branch Hospital over a 14-month period. Eleven of these patients were candidates for operation because of intractable pain (two had bled recently as well). One of these eleven was a woman; 10 were men, and their ages ranged from 23 to 59 years. The diagnosis of duodenal ulcer was confirmed by upper gastrointestinal barium x-ray studies and by fiberoptic gastroduodenoscopy. The duration of the patients' symptoms ranged from 6 months to 10 years. Five patients had previously bled from the upper gastrointestinal tract and two had had a perforated ulcer. All patients underwent elective selective proximal vagotomy; none of the patients in the group were operated on as an emergency and none had signs or symptoms of gastric outlet obstruction. We will compare the results of acid secretory and

FIG. 1. Schema of intragastric titration technique (reproduced with permission from Thompson JC and Swierczek JS, Annals of Surgery 186:541-548, 1977).

Ann. Surg. X October 1978

serum gastrin measurements in the above 11 patients treated by selective proximal vagotomy with those of nine patients operated on for symptoms of gastric outlet obstruction. Of the remaining nine, five were women and four were men, and their ages ranged from 22 to 63. Their symptoms ranged in duration from 2 months to 12 years. Two patients had bled previously and one patient had undergone previous perforation. All patients had clear symptoms and signs of chronic gastric outlet obstruction. In every case, this was confirmed by upper gastrointestinal barium roentgenography, gastroscopy, and saline load testing.5 In addition to the roentgenographic and endoscopic examination, each patient also had a standard gastric analysis, in which the basal acid output and the maximal acid output to Histalog (betazole, 1.5 mg/kg) was determined. Each patient underwent measurement of acid secretion by a technique of intragastric titration described previously.30 This method, a modification of the technique of Fordtran and Walsh,4 will be described briefly for clarity (Fig. 1); it allows continuous measurement of gastric secretory responses to the intragastric instillation of an amino acid meal. For the present study, we have used 400 ml of a 5% amino acid solution (caseine hydrolysate + 1% DL-tryptophan, Stuart Pharmaceuticals, Wilmington, Delaware) adjusted to 300 mosm. Continuous mixing of the test meal substance was achieved with a Harvard® peristaltic pump which continuously circulated the liquid from the stomach via a biluminal nasogastric tube to an 800 ml titration chamber. A reservoir, which functioned both as a barostat and as a safety valve, was connected to the reinfusion tube and was maintained at 20 cm above the supine patient. The intragastric pH was maintained at any selected level by means of a pH-stat assembly consisting of a glass calomel electrode inserted into the titration chamber and connected to a pH meter, titrator and autoburette which delivered 1.0 N NaOH. Acid output was calculated from the amount of NaOH required to maintain the preselected pH. In the intragastric titration study, patients underwent measurement of two basal specimens of 30 minutes each, after which the amino acid solution was introduced at pH 5.5 for one hour. The solution was then removed, the pH was adjusted to 2.5 and the solution was returned for one hour. The process was repeated, the pH adjusted to 1.5 and the solution was returned for one more hour. Blood samples were obtained for measurement of gastrin by radioimmunoassay'0 before the introduction of the test meal and at 30, 60, and 90 minutes after introduction of the meal. Acid secretory values are available on all patients at all periods, but some gastrin samples were lost in

VOl. 188.* NO. 4

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SELECTIVE PROXIMAL VAGOTOMY

processing so that complete gastrin data are available on nine patients who underwent selective proximal vagotomy and six patients who underwent truncal vagotomy. The technique for selective proximal vagotomy has been described.6'4 We have been careful to heed the admonition of Hallenbeck and colleagues8 to elevate the vagal trunks carefully from the esophagus and to divide all branches from the vagi to the intraabdominal portion of the esophagus. Additionally, we have carefully denervated the area of the angle of His and have searched for all nerves going to the left ofthe esophagus to the fundus. All patients were operated upon by one surgeon (JCT). The second group of patients underwent standard truncal vagotomy with creation of an anterior gastrojejunostomy placed immediately proximal to the pylorus. Intragastric titration studies were repeated at two to six weeks after operation in all patients. We have late intragastric titration studies (6-12 months postoperative) in four patients. Informed consent for participation in the study was obtained from each person. The protocol for the entire study was approved by the Research Committee for the Protection of Human Subjects of The University of Texas Medical Branch. Results are expressed as the mean plus or minus one standard error. Except where noted, the Student's t-test was used to analyze the data for statistical significance of differences between means. Differences with a p value of less than 0.05 were considered significant. Where indicated, data were analyzed by analysis of variance.25 Results There were no deaths and no serious complications in the 20 patients operated upon. In the short time that they have been followed postoperatively, all patients have had excellent clinical results. The patients operated upon by selective proximal vagotomy have been entirely asymptomatic. Two of the patients who underwent truncal vagotomy plus gastroenterostomy for gastric outlet obstruction had difficulty with gastric emptying in the early postoperative period. Normal emptying resumed spontaneously in both. Good stimulation of acid secretion was achieved by intragastric titration at pH 5.5. Much smaller amounts of acid were made at pH 2.5 and 1.5. At pH 5.5, the maximal acid output (MAO) in 11 selective proximal vagotomy (SPV) patients was 17.4 + 3.1 mEq/hour. This was 49% of the MAO to Histalog (35.5 + 5.7 mEq/ hour) in the same patients (Fig. 2). The intragastric secretory output at pH 5.5 was 21.6 + 3.4 in nine patients prior to truncal vagotomy plus drainage

TV+D

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HISTALOG

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HISTALOG MAO PREOP

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FIG. 2. Comparisons of preoperative maximal acid output (MAO) in 11 patients later treated by selective proximal vagotomy (SPV) and nine patients later treated by truncal vagotomy and drainage (TV + D) in studies using Histalog and intragastric titration at pH 5.5.

(TV + D). This was 55% of the Histalog MAO (43.8 ± 4.7 mEq/hour). Significant reductions in acid output measured by intragastric titration at pH 5.5 were achieved after both selective proximal vagotomy and truncal vagotomy plus drainage (Fig. 3). Preoperative acid output at pH 5.5 ranged from 4.6 to 36.3 mEq/hour in the SPV patients. After operation, secretory values ranged from 0.1 to 11.1 mEq/hour. Preoperative acid secretory levels at pH 5.5 ranged from 4.3 to 37.0 mEq/hour in nine patients who were operated upon by truncal vagotomy plus drainage. After operation, these patients secreted between 0.7-15.9 mEq/hour. The average preoperative secretory output at pH 5.5 was 17.4 + 3.1 mEq/hour in the SPV patients and 21.6 + 3.4 mEq/hour in the obstructed patients who later under40

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POSTOP PREOP POSTOP pH 5.5 pH 5.5 FIG. 3. Individual preoperative and postoperative acid secretory responses as measured by intragastric titration at pH 5.5 in 11 patients treated by selective proximal vagotomy (SPV) and nine patients treated by truncal vagotomy plus drainage (TV + D). PREOP

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went truncal vagotomy (Fig. 4). After operation, the SPV patients had an average acid output of 4.3 + 1.1 mEq/hour for a mean reduction of 72%; after truncal vagotomy and drainage, the average acid output was 7.3 + 2.1 mEq/hour for an average acid reduction of 67%. The degree of acid reduction in patients studied by intragastric titration at pH 2.5 and 1.5 was similar in the two operative procedures, but slightly greater with SPV (Fig. 5). The majority of patients made negligible amounts of acid pre- and postoperatively at the lowest pH level. We obtained later (6-12 months) repeat studies of intragastric secretory measurements in four SPV patients. The average preoperative acid output at pH 5.5 was 17.1 + 1.8 mEq/hour, which fell to 5.9 ± 2.1 mEq/hour in the early postoperative studies. Between the early and later postoperative studies, secretory values rose in two patients and fell in two, but the average changed only slightly (6.3 ± 2.5 mEq/hour). One patient, who showed a good reduction in the early postoperative study, had a return of acid secretion nearly to the preoperative level in the later study. The 5% amino acid solution proved to be only a fair stimulant of gastrin release. Preoperatively, gastrin values in nine patients who underwent SPV rose from a basal level to 60.9 ± 5.9 pg/ml to a peak of 81.4 ± 10.0 pglml at 60 minutes (Fig. 6). At 90 minutes (which was 30 minutes after the pH had been lowered to 2.5) the gastrin value fell to 71.8 ± 6.8 pg/ml. Postoperative stimulated gastrin values in the same patients were significantly higher when tested by analysis of variance; SPV

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the basal level of 90.6 ± 4.6 pg/mI rose to 108 ± 13 pg/ml at 60 minutes and 112 + 12.9 pg/ml at 90 minutes. The preoperative gastrin values of the obstructed patients who underwent truncal vagotomy and drainage were significantly higher than those of the SPV patients

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Effect of selective proximal vagotomy and truncal vagotomy on gastric acid and serum gastrin responses to a meal in duodenal ulcer patients.

ANNALS Vol. 188 OF SURGERY October 1978 No. 4 Effect of Selective Proximal Vagotomy and Truncal Vagotomy on Gastric Acid and Serum Gastrin Respon...
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