World J. Surg. 3, 235-240, 1979

Interrelationship between Serum Gastrin Concentration, Gastric Acid Secretion, and Gastric Emptying Rate in Recurrent Peptic Ulcer Erik Amdrup, M.D., Ph.D., Margrethe Brandsborg, M.D., Ole Brandsborg, M.D., and Nils Axel L0vgreen, M.D. SurgicalGastroenterologicalDepartmentL, Kommunehospitalet,Aarhus, Denmark hypergastrinemia is not a frequent finding in patients with recurrent ulcer. The present study concerns 36 patients admitted to the hospital between 1973 and 1977 for recurrent ulcer after surgery performed in this or other departments for ulcer in the duodenal bulb (DU), pyloric ring (PU), or immediate prepyloric region (PPU). Two further patients with gastrinoma are not included. Before reoperation, the fasting and food-stimulated serum gastrin concentrations, gastric acid secretion, and gastric emptying rate were measured.

In 36 patients with recurrent peptic ulcer after surgery (11 partial gastrectomy, 25 vagotomy with or without drainage), 12 had a gastric and 24 an intestinal recurrence. Gastric recurrence after partial gastrectomy was characterized by retained antral tissue and a marked serum gastrin response to feeding. Fasting serum gastrin concentration and gastric acid secretion were not correlated with the location of the recurrent ulcer. Gastric recurrences in patients treated by vagotomy correlated mainly with prolonged gastric emptying, and basal acid secretion was significantly lower than in patients with intestinal recurrence. Following complete vagotomy, the recurrence was usually gastric, but it was intestinal after incomplete vagotomy. In the vagotomy group, no correlations between location of ulcer and pentagastrin-stimulated acid secretion, or fasting and foodstimulated serum gastrin concentrations were found.

Patients

Thirteen of the 36 patients were women. The mean age of the group was 52 years (range 32-80 years). The initial operation was performed a mean of 56 months previously (range 5-108 months). The primary ulcer was a DU in 18 patients, PU in 7, and PPU in 11 patients. Eleven patients (6 with DU, 2 with PU, and 3 with PPU) had been treated by partial gastrectomy and gastrojejunal anastomosis. In 25 patients, a vagotomy had been performed. The vagotomy was a truncal vagotomy and drainage (TV) in 12, selective gastric vagotomy and drainage (SGV) in 3, and parietal cell vagotomy without drainage (PCV) in 10. Chronic epigastric pain was the principal reason for admission of 28 patients, 14 complained of vomiting, 6 were admitted for bleed-

When an ulcer does not heal or recurs following surgery, it suggests that the operation was inadequate. However, in some patients with ulcer recurrence, the operation was technically satisfactory according to all observed criteria, including results of objective investigations that are indistinguishable from those obtained in symptom-free patients treated in the same way and for the same type of ulcer. In these patients, biological causes may be suspected. The classic example is the gastrinoma. However,

Supported by grants from the Danish Medical Research Council (no. 512-7093). Reprint requests: Erik Amdrup, M.D., Ph.D., Surgical Gastroenterological Dpt. L. Kommunehospitalet, Dk8000 Aarhus C., Denmark.

0364-2313/79/0003-0235 $01.20 9 1979 Soci6t6 Internationale de Chirurgie 235

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World J. Surg. Vol. 3, No. 2, 1979

Table 1. Ulcer recurrence after partial gastrectomy in 11

patients.

Serum gastrin pg / ml

Pentagastrin Location of Location of Basal acid peak acid primary ulcer recurrence output--mEq output--mEq Duodenum Duodenum Duodenum Duodenum Duodenum Duodenum Pylorus Pylorus Prepyloric Prepyloric Prepyloric

Intestine Intestine Intestine Stomach Stomach Stomach Intestine Stomach Intestine Intestine Intestine

0 0.16 0.8 0.26 0 1.34 2.67 0 1.22 0.25 0

6.24 12.34 6.28 4.20 0.08 4.12 8.00 0 34.56 2.30 0

ing, and 1 was admitted for perforation. The patients were questioned thoroughly for use of salicylates and other drugs, alcohol, and smoking. The examination did not reveal any likelihood that these factors were o f importance in ulcer recurrence.

Methods

The diagnosis was based on endoscopy with biopsy, supported by double contrast radiological examination, and was confirmed at laparotomy. Separation o f the location of ulcer recurrence into gastric and intestinal was based on macroscopic and histologic examinations. In all vagotomized patients, the function o f the vagus nerve was evaluated by an insulin test. The fasting stomach was aspirated for 15 minutes, after which basal acid output (BAO) was measured for four 15-minute periods. Insulin in a dose of 0.2 U/kg was given intravenously and followed by aspiration of the stomach for eight 15-minute periods. Adequate hypoglycemia, with a blood glucose level less than 40 mg/dl, was obtained in all patients. Titration of the gastric juice to pH 7.0 with 0.1 N a O H was performed with an automatic titrator (Radiometer, Copenhagen). When insulin did not result in any rise in gastric acid secretion compared to BAO, the vagotomy was considered complete. If peak acid output (PAO') rose 2 mEq or more o v e r BAO, vagotomy was considered incomplete. A smaller rise placed the patient in an intermediate group. A pentagastrin test, using pentagastrin in a dose o f 10/xg/kg was performed as described above in both resected and vagotomized patients. The gastric emptying rate was estimated from clinical symptoms of gastric stasis, and by x-ray examination for barium retained in the stomach 6

20-

-1'5

15 3'o

66

9b 165 l 0Min.

Fig. 1. Fasting and food-stimulated serum gastrin concentration in 11 patients with recurrent ulcer after partial gastrectomy. Meal intake was at time 0. Results are mean values + SEM.

hours after intake of 150 g regular barium suspension. Serum gastrin concentration (SGC) was measured in the basal state and after a standard test meal (beef weighing 150 g and containing 30 g protein and 20 g fat). This meal was consumed in approximately 5 minutes by all subjects.

Surgical T r e a t m e n t

Patients with an intestinal recurrence after partial gastrectomy were treated with selective vagotomy of the gastric remnant as described previously [1]. The stomach was not opened. Retained antral tissue was searched for with an intragastric pH-electrode, but was not found in any patient. When recurrence was gastric in location, the anastomosis was opened, acid secretion was stimulated with pentagastrin, and the mucous membrane painted with Congo red dye. The red-colored antral tissue was then resected, while the black-stained corpus was vagotomized and reanastomosed to the intestine. In vagotomized patients, no attempt to perform a revagotomy was undertaken. All of these patients were treated with antrectomy. Efforts were made to perform antrectomy precisely [2], i.e., to remove all antral tissue but nothing more. In most patients, the antrum/corpus border was located by using an intragastric pH-electrode during pentagastrin stimulation o f acid secretion. When this method failed, Congo red painting was employed through a gastrotomy. An evaluation o f the results o f the secondary surgical treatment is not part of this report. For statistical evaluation, the Wilcoxon test for unpaired differences was used.

E. Amdrup et al.: Recurrent Peptic Ulcer

237

Serum gastrin pg/ml

Gastric acid secretion meq/ h

Serum gastrin pg ml

100-

20

80

i

60

40

200

15

10-

I00-

20-

5-1.5

b

1'5 36

4'5

6b

7~

90

105 I20Min.

Fig. 2. Serum gastrin concentration (o--o) in 3 patients with gastric recurrence after partial gastrectomy. The response to a meal, given at time 0, was eliminated after resection of the retained antral tissue (.--e). Only the patient with the largest gastrin response had stasis before surgery.

Results

Recurrence after Partial Gastrectomy In 4 of the 11 patients, the recurrent ulcer was located in the stomach, while in the rest, it was located in the intestine. The 4 recurrent gastric ulcers were located in the antrum of the stomach remnant. The only patient with clinical and radiologic gastric stasis was in this group. This patient had no basal or stimulated gastric acid secretion, while in the other patients, acid secretion was variable and unrelated to either the location o f the primary or the recurrent ulcer (Table 1). The basal SGC was within the normal range in all patients and the mean rise after food intake was negligible (Fig. 1). H o w e v e r , the individual tests o f 3 patients differed from the rest. They all had a recurrent ulcer in the gastric antrum and showed a marked gastrin response to the meal. This response was eliminated by resection of the retained antral tissue (Fig. 2).

Recurrence after Vagotomy Eight of these recurrent ulcers were gastric, and the rest were intestinal in location. There was no rela-

BAO PAO I--I Intestinal Recurrence

Basal Peak " " m Gastric Recurrence

Fig. 3. Basal acid output (BAO) and peak acid output

(PAO) after pentagastrin and the basal and peak mealstimulated serum gastrin concentrations in 25 patients with recurrent ulcer after vagotomy. BAO was significantly less in patients with gastric recurrence than in those with intestinal recurrence. The other differences are not significant. Results are mean values -+ SEM.

tionship between the site of the original and the recurrent ulcer. BAO was significantly less in patients with gastric recurrence than in those with intestinal recurrence (p < 0.05). PAO P was not significantly lower in patients with gastric recurrence. This was also true for the fasting and food-stimulated peak in SGC (Fig. 3). Basal SGC did not correlate with BAO or the aspirated volume. Nine patients had no rise in gastric acid secretion after insulin, and their vagotomy was considered complete. In all others, the rise in PAO I was more than 2 mEq/h, and vagotomy was considered incomplete. Fig. 4 relates the completeness o f ~agotomy to the location of the recurrent ulcer and indicates that ulcer recurrence was usually gastric in location in patients with a complete vagotomy, while an intestinal recurrence was characteristic of patients with an incomplete vagotomy. Gastric recurrence was an exception when the stomach emptied normally, i.e., within 6 hours, but was the most frequent type of recurrence w h e n gas-

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World J. Surg. Vol. 3, No. 2, 1979

["-'I Intestinal Recurrence I Gastric Recurrence

No. of Patients

No. of Patients

15[ ~ ] Intestinal Recurrence 1 Gastric Recurrence I0-

lO

5-

Complete I nc0mplete VAGOTOMY Fig. 4. Gastric and intestinal ulcer recurrence in 25 patients treated with vagotomy. Complete refers to no rise in gastric acid secretion following insulin. Incomplete refers to a rise in peak acid output of 2 mEq/h or more compared to basal secretion.

Serum gastrin pgl ml 1.50

Fig. 5. Gastric emptying time related to location of recurrent ulcer in 25 patients with ulcer recurrence after vagotomy.

Discussion

i00-

50-

|9

9

$ m



h

EMPTYING TIME Fig. 6. Difference between serum gastrin concentration at 120 minutes after a meal and the basal values (A serum gastrin) in relation to gastric emptying rate.

tric e m p t y i n g time was prolonged (Fig. 5). In Fig. 6, gastric emptying rate is related to SGC 120 minutes after a meal. O f the 14 patients with normal gastric emptying, only 1 had a SGC higher than 50 pg/ml. I f this patient is excluded, the difference is significant.

Ulcer recurrence follows any type of surgery that leaves part of the stomach in place. The frequency varies. E v e n v a g o t o m y and a n t r e c t o m y has a definite, although small, recurrence rate. O f 11 patients with recurrent ulcer after partial g a s t r e c t o m y , 4 had a gastric recurrence in antral tissue left behind at the p r i m a r y operation. Three of these showed a m a r k e d rise in SGC after a meal, and this was eliminated b y antral resection. One of these patients had gastric stasis, the only one in the resected group. All had acid secretion within the normal range. The retained antral tissue was p r e s u m a b l y the reason for the recurrence in these 4 patients. Seven patients with no antral tissue had a normal SGC that did not change after food intake, and they had a normal gastric e m p t y i n g rate. Acid secretion remained the only explanation for their intestinal recurrence. It has to be added, h o w e v e r , that acid secretion was e x t r e m e l y variable, so m u c h so that other causes of ulcer recurrence might be suspected. No distinction was detected b e t w e e n the various types of v a g o t o m y used in 25 patients. In those with gastric recurrence, B A G was lower, but there was no difference in stimulated acid secretion b e t w e e n patients with gastric and intestinal recurrence. The most characteristic differences were that it was infrequent to have a gastric recurrence when s t o m a c h emptying was normal, and that an incomplete vag o t o m y usually was associated with intestinal recurrence. Thus, a p o o r v a g o t o m y increases the risk

E. Amdrup et al.: Recurrent Peptic Ulcer

for intestinal recurrence, and poor gastric emptying for gastric recurrence. As previously reported [3] and in keeping with other reports [4, 5], a positive correlation exists between a prolonged gastric emptying rate and increased integrated serum gastrin output after meals. This relationship was also observed in the present study. However, in spite of this and the positive correlation between a prolonged gastric emptying rate and recurrence of ulcer in the stomach, the patients with gastric recurrence did not show higher fasting or peak SGC. In patients with recurrent ulcer, determination of the location of the recurrent ulcer, SGC, BAO, insulin response, and gastric emptying rate may be helpful for evaluating the cause of recurrence and perhaps, also for deciding on the treatment.

R~sume Sur 36 malades pr6sentant une r6cidive ulc6reuse apr6s gastrectomie (11 cas) ou apr6s vagotomie avec ou sans drainage (25 cas), l'ulcEre r6cidivant 6tait localis6 /t l'estomac dans 12 cas, ~i l'intestin dans 24. La r6cidive gastrique apr6s gastrectomie est caract6ris6e par la pr6sence de muqueuse antrale laiss6e en place et par une 616vation nette de la gastrin6mie lors du repas d'6preuve. La gastrin6mie ~ijeun et la s6cr6tion chlorhydrique sont sans relation avec la localisation de l'ulc6re rEcidivant.

Invited Commentary Charles G. Clark, M.D., Ch.M., F.R.C.S. University College Hospital Medical School, London, England

Amdrup's interesting observations on recurrent ulceration after surgery for duodenal, pyloric, and prepyloric ulcers attempts to define possible correlations that might determine whether the recurrence is gastric or intestinal. There is a fundamental problem, of course, as to what determines the location of the primary ulcer. All 3 types of ulcer behave similarly with respect to symptoms, and acid secretion follows the duodenal ulcer pattern of either normal or elevated output, whereas in the common variety of lesser curve gastric ulcer, acid output is low. Thus, we have no means of determining by

239

La r6cidive gastrique apr~s vagotomie est caract6ris6e, en g6n6ral, par un allongement du temps de vidange gastrique et une acidit6 basale nettement plus basse qu'en cas de r6cidive intestinale. Apr6s vagotomie compl6te, la r6cidive est en g6n6ral gastrique; apr6s vagotomie incompl6te, elle est intestinale. Dans le groupe des malades vagotomis6s, nous n'avons pas trouv6 de corr61ation entre la localisation de l'ulc6re, la r6ponse s6cr6toire acide ~i la pentagastrine, la gastrin6mie /t jeun et apr~s repas d'6preuve.

References 1. Amdrup, E.: Selective vagotomy of the gastric remnant for extragastric ulcer recurrence following resection. Scand. J. Gastroenterol. 6:489, 1971 2. Amdrup, E., Kragelund, E., Jensen, H.-E.: Precise antrectomy for gastric ulcer. Acta Chir. Scand. 138:517, 1972 3. Brandsborg, O., Brandsborg, M., L0vgreen, N.A., Mikkelsen, K., M0ller, B., Rokkjaer, M., Amdrup, E.: Influence of parietal cell vagotomy and selective gastric vagotomy on gastric emptying rate and serum gastrin concentration. Gastroenterology 72:212, 1977 4. Feurle, G., Ketterer, H., Becker, H.D., Creutzfeldt, W.: Circadian serum gastrin concentrations in control persons and in patients with ulcer disease. Scand. J. Gastroenterol. 7:177, 1972 5. Jaffe, B.M., Clendinnen, B.G., Clarke, R.J., Alexander Williams, J.: Effect of selective and proximal gastric vagotomy on serum gastrin. Gastroenterology 66:944, 1974

measurements of acid secretions, gastrin levels, blood groups, etc., in the untreated state, why the primary ulcer should be on one or the other side of the pyloroduodenal junction (or in the canal). This may be why there is no complete separation into clear subgroups of the patients with ulcer recurrence after surgery. There is a methodological problem regarding the accuracy of gastric secretory studies, particularly after Polya gastrectomy. The accuracy of measurement, particularly after vagotomy, can be greatly improved by methods that take into account pyloric loss and duodenal reflux [1]. The 4 gastric ulcer recurrences after partial gastrectomy showed low basal and pentagastrin-stimulated secretions in accordance with other observations [2]. All had a retained portion of antrum that may have been the cause of ulcer recurrence, but the evidence of antral stimulation in response to a meal is visually con-

Interrelationship between serum gastrin concentration, gastric acid secretion, and gastric emptying rate in recurrent peptic ulcer.

World J. Surg. 3, 235-240, 1979 Interrelationship between Serum Gastrin Concentration, Gastric Acid Secretion, and Gastric Emptying Rate in Recurrent...
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