Effect of Biliary Reconstruction Procedures on Gastric Acid

Secretion

Toshio Sato, MD, FACS, Sendai, Japan

Mikio Imamura, MD, Sendai, Japan

lwao Sasaki, MD, Sendai, Japan

Jinichi Kameyama, MD, Sendai, Japan

Gastric acid hypersecretion and the development of peptic ulcer after Roux-Y choledochojejunostomy have been reported by various researchers, and many of them stressed the importance of biliary diversion as the mechanism of postoperative peptic ulceration. The incidence of peptic ulcers as well as changes in gastric acid secretion were studied in our series of patients who underwent Roux-Y choledochojeju- nostomy. Postoperative changes in gastric acid se- cretion were also studied in patients who underwent jejcnal interposition choledochoduodenostomy. In these patients, changes in serum gastrin and secretin levels were also assessed.

Patients and Methods

From April 1961 to December 1980, biliary tract recon- struction procedures were performed in a total of 58 pa- tients with benign biliary diseases. These included 37 pa- tients with Roux-Y choledochojejunostomy (Group I) and 10 patients with jejunal interposition choledochoduode- nosl;omy (Group II). A jejunal segment of 15 cm in length was interposed and anastomosed side-to-end to the hepatic duct and end-to-side to the second portion of the duo- denum. Follow-up studies were available in 26 of the 37 patients in Group I and in all of the patients in Group II. Primary diseases in the patients were congenital chole- dochal dilatation in 20, postoperative bile duct stenosis in 9, stricture at the site of bilioenteric anastomosis in 6, and intrsoperative bile duct injury in 1. Their ages ranged from 15 to 70 years in Group I with an average age of 36 years and 19 to 66 years in Group II with an average of 45 years. Average periods of postoperative observation were 8 years for patienis in Group I and 1 year and 8 months for patients in Group II. Since there was much inconsistency in indi- vidual observation periods, a certain number of patients who had nearly equal observation periods were picked from the two groups and were subjected to comparative study.

Tetragastrin, 4 pg/kg, was injected intramuscularly to stimulate gastric secretion. Gastric acid concentration was

From the Department of Surgery, Tohoku University School of Medicine, Sendai, Japan.

Requests fw reprints should be addressed to Toshio Sate, MD, Department of Surgery, Tohoku University, School of Medicine, Sendai 980, Japan.

determined by titration with 0.1 N sodium hydroxide using TBpfer’sTeagent as an indicator. Maximum acid output was also measured before operation and at the time of follow-up, and the levels of the two grotips at follow-up were also compared. In addition, a test meal of 300 g of rice gruel and an egg, carbohydrates 70.9 percent, protein 16.4 percent, fat 10.7 percent, was given to each patient at the time of follow-up, and peripheral blood was sampled at fasting and at 15,30, and 60 minutes after feeding. Gastrin and secretin levels were determined in each blood sample and were compared between the two groups. Serum gastrin and secretin levels were measured by radioimmunoassay with an assay kit (available from CEA-IRA-SORIN Association, Gif-Sur-Yvette, France, and from Daiichi Radioisotope Laboratory, Tokyo, Japan). The determined values were expressed as mean f standard error of the mean and the significant difference by Stu- dent’s t test, with p <0.05 stipulated as significant.

Results

Changes in gastrin-stimulated maximum acid output: As shown in Figure 1, maximum acid output in patients with jejunal interposition choledocho- duodenostomy was 2.3 f 0.8 mEq/h before operation and 4.9 f 1.5 mEq/h at follow-up, whereas in patients with Roux-Y choledochojejunostomy, the corre- sponding levels were 2.1 f 0.8 mEq/h and 5.6 f 1.4 mEq/h, respectively. In both groups, the levels at follow-up were higher than those before operation, with increase ratios of 213 percent for Group II and 266.7 percent for Group I. However, there were no significant differences between preoperative and follow-up levels in either group, nor were there any significant differences between the two groups in their levels at follow-up.

There were nine patients in Group II who had comparable postoperative observation periods and seven in Group I. In Figure 2 the changes in levels of maximum acid output before operation and at fol- low-up in both groups are shown. The mean values were 2.3 f 0.8 mEqk before operation and 5.5 f 1.5 mEq/h at follow-up in Group II, and 3.2 f 1.3 mEq/h and 8.8 f 2.8 mEq/h respectively, in Group I. In both groups, the levels at the time of follow-up were higher

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Sat0 et al

MAO hEq hr)

(M+SEM)

T 213% .

Before Operation

% Increase Ratio

T 267%

INTERPOSITION ROUX-Y (n=lO) in=261

Figure 1. Changes ot gastrln-stimulated maximum acid output (MAO). InterposItIon = jejunal interposition choledochoduode- nostomy; Roux-Y = Roux-Y choledochojejunostomy.

MAO (mEq hrl

INTERPOSITION (n=9)

3efore At lperation Follow-up

than those before operation with increase ratios of 238.8 percent in Group II and 275.5 percent in Group I. The follow-up levels of maximum acid output and increase ratio tended to be slightly higher in patients with Roux-Y choledochojejunostomy than in those with jejunal interposition choledochoduodenostomy. However, the differences in maximum acid output levels were not significant between preoperative and follow-up levels in either group, and there were no significant differences in follow-up levels between the two groups.

Changes in serum gastrin levels: As shown in Figure 3, the serum gastrin levels in patients with jejunal interposition choledochoduodenostomy (Group II) at the time of follow-up were 64.5 f 12.2 pg/ml at fasting and 173.8 f 38.4,146.4 f 27.5, and 132.6 f 28.2 pg/ml at 15, 30, and 60 minutes, re- spectively, after feeding, whereas in patients in Group I with Roux-Y choledochojejunosto&y, the corresponding levels were 58.9 f 7.7 at fasting, and 124.2 f 20.8,112.3 f 17.9, and 92.2 f 14.5 pg/ml at 15,30, and 60 minutes, respectively, after feeding. In both groups, the levels were the highest at 15 minutes and substantially decreased thereafter. The levels that were significantly higher after feeding than at fasting were found at 15,30, and 60 minutes in pa- tients in Group II and at 15 and 30 minutes in pa- tients in Group I. Although the serum gastrin levels were higher in patients with jejunal interposition choledochoduodenostomy (Group II) at each time of measurement, it was evident that the difference at any point was not significant between the two groups.

P , 8’

,’

Before At Operation Follow-up

Figure 2. Changes of gastrin-stimulated ROUX-Y maximum acid output (MAO) In patients

(n=7) with nearly equal observation periods.

The American Journal of Surgery

Biliary Reconstruction and Gastric Acid Secretion

.-a Interposition (n= 9 1

~-------~ Roux-Y in=121

IRG (w ml)

200

100

Figure 3. Changes of serum gas&in bevels. 0 IRG = immunoreactlve gastrln.

Test Meal

(M+SEM)

0

Changes in serum secretin levels: The serum secretin levels in Group II at the time of follow-up, as shown in Figure 4, were 101.3 f 14.1 pg/ml at fasting, and 103.1 f 15.4, 121.6 f 29.2, and 101.1 f 15.9 pg/ml at 15, 30, and 60 minutes, respectively, after feeding, whereas the corresponding levels in patients in Group I were 111.2 f 17.9 pg/ml at fast- ing, and 119.6 f 17.9, 148.7 f 35.4, and 128.6 f 17.9 pg,‘ml 15, 30, and 60 minutes, respectively, after feeding. In both groups, only a slight increase in the level could be seen at 30 minutes after feeding. There was a tendency for serum secretin levels to be higher in patients with Roux-Y choledochojejunostomy than in those with jejunal interposition choledochoduo- denostomy. However, the difference was insignificant between the two groups at any point of measure- ment.

Postoperative peptic ulcers: No instance of postoperative peptic ulcers could be detected in ei- ther group of patients.

Comments

Recently, the development of peptic ulcer after choledochojejunostomy has stimulated many re- searchers to reevaluate the conventional procedures of biliary tract reconstruction. Aust et al [1] has al- ready insisted that choledochoduodenostomy is preferable to choledochojejunostomy, particularly because of the lower incidence of postoperative peptic ulcers associated with it. Nielsen et al [2] also noted that postoperative gastric acid hypersecretion

was more distinct after choledochojejunostomy than after choledochoduodenostomy. Thus, choledocho- duodenostomy may be the more favorable procedure for biliary tract reconstruction. Choledochoduode- nostomy, however, still involves various problems such as difficulty of anastomosis and liability to retrograde cholangitis. In coping with such disad- vantages, Wheeler and Longmire [3] recommend jejunal interposition choledochoduodenostomy de- vised by Grassi et al [4] as a safe and effective pro- cedure.

Follow-up studies of our patients with Roux-Y choledochojejunostomy revealed no instance of postoperative peptic ulcers. Nonetheless, attention should be paid to the tendency of gastric acid hy- persecretion to develop, as was noted at the time of follow-up in our patients who had Roux-Y choledo- chojejunostomy. Sekine et al [5] of our department found that after cholecystojejunostomy, dogs dem- onstrated marked gastric acid hypersecretion. In an attempt to evaluate jejunal interposition choledo- choduodenostomy, we have used this type of opera- tion since 1977 in a total of 10 patients. To date, there is no comparative study concerning the change in gastric acid secretion following the Roux-Y chole- dochojejunostomy or the jejunai interposition cho- ledochoduodenostomy.

In an attempt to study this problem, gastric acid secretion was measured after each of these two pro- cedures. In both groups, the levels of gastrin-stimu- lated maximum acid output at the time of follow-up

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Sat0 et al

- Interposition (n= 9 1

c+----4 Roux-Y (n=12)

IRS b9 ml)

200 -

100.

0

rest Meal --__ --__ --- 4

I I I

(M+SEM) 1 Flgure 4. Changes of serum secretin lev-

0 15 30

tended to be higher than before operation. The fol- low-up levels of maximum acid output were higher in patients with Roux-Y choledochojejunostomy than in those with jejunal interposition choledochoduo- denostomy, but there was no significant difference. The increase ratios in maximum acid output were 213 percent in Group II (jejunal interposition choledo- choduodenostomy) and 266.7 percent in Group I (Roux-Y choledochojejunostomy). Similar results were obtained in the patients who had comparable postoperative observation periods. It is interesting to note that the patients with jejunal interposition choledochoduodenostomy, a type of operation that is free of biliary diversion, also showed gastric acid hypersecretion at the time of follow-up.

Loss of neutralizing action of bile within the duo- denum and postoperative gastric acid hypersecretion are suspected as possible mechanisms for the devel- opment of peptic ulcer after biliary diversion. For the loss of the neutralizing action within the duodenum, a recent report indicated the mechanism by which bile stimulates exocrine secretion of the pancreas [6]. Thus, biliary diversion from the duodenum results in failure of the intraduodenal neutralization.

In regard to postoperative gastric acid hyperse- cretion, investigations have recently been conducted about the effects of both gastric secretory stimulants and inhibitors. As for the positive effects of gastric

60mln e/i. IRS = lmmunoreactlve secretin.

secretory stimulants, Nielsen et al [2] reported the augmented biosynthesis and release of gastrin in the antral mucosa of patients who had undergone Roux-Y choledochojejunostomy. In our study, how- ever, the serum gastrin levels were higher in patients with jejunal interposition choledochoduodenostomy than in those with Roux-Y choledochojejunostomy, although the differences were not significant. This finding makes it difficult to explain the higher levels of gastric acid secretion that were observed more often in patients with Roux-Y choledochojejunos- tomy than in those with jejunal interposition chole- dochoduodenostomy. It may be assumed that the increase in the serum gastrin level represents the result of a feedback in response to changes in gastric acid secretion rather than the cause of postoperative gastric acid hypersecretion. In other words, the in- fluence of some substance other than gastrin should be considered as the mechanism of gastric acid hy- persecretion following biliary tract reconstruction procedures. Sekine et al [5] presumed the existence of some gastric secretory stimulants other than gas- trin that were released as a result of direct flow of bile into the upper jejunum. Orloff et al [7] proposed the intervention of intestinal phase hormone.

Regarding the influence of gastric secretory in- hibitors, it is presumed that there may be a loss of various gastric inhibitory substances including se-

552 The American Journal of Surgery

Biliary Reconstruction and Gastric Acid Secretion

cretin, cholecystokinin, gastric inhibitory polypep- tide, vasoactive intestinal polypeptide, and serotonin, which are believed to exist in abundance in the upper intestine [8-101. In patients with jejunal interposition choledochoduodenostomy and in those with Roux-Y choledochojejunostomy, a kind of blind loop is formed in the upper intestine which keeps no direct contact with thyme. This may well lead to the de- creased secretion of these gastric inhibitors. In the present series, the levels of serum secretin usually ten.ded to be higher in patients with Roux-Y chole- dochojejunostomy than in those with jejunal inter- position choledochoduodenostomy, though the dif- ference was insignificant. Thus, the changes in serum secretion did not correspond to the trend of gastric acid secretion, which was usually higher in patients with Roux-Y choledochojejunostomy than in those with jejunal interposition choledochoduodenostomy. The changes in serum secretin levels following biliary tract reconstruction procedures were likely to relate to the degree of intraduodenal acidification. There- fore, if the mechanism of gastric acid hypersecretion following biliary tract reconstruction procedures is to be traced to a loss of gastric secretory inhibitors, it rnay be essential to consider the intervention of some substance with enterogastrone activity other than secretin [I I).

Summary

In 26 patients with Roux-Y choledochojejunos- tomy and 10 with jejunal interposition choledocho- duodenostomy, gastrin-stimulated gastric acid se- cretion and serum levels of gastrin and secretin after feeding were examined before operation and at the time of follow-up.

The follow-up levels of maximum acid output were higher than those before operation in each group, and they tended to be higher in patients with Roux-Y choledochojejunostomy (Group I) than in those with jejunal interposition choledochoduodenostomy

(Group II), but the difference was not significant. There was no instance of postoperative peptic ulcer in either group. The levels of serum gastrin after feeding tended to be higher in Group II, whereas serum secretin levels were contrarily higher in Group I. The changes in these hormones could be considered not as the cause but rather as the outcome of the changes in postoperative gastric acid secretion.

References

1. Aust JB, Root HD, Urdaneta L, Varco RL. Biliary stricture. Surgery 1967;62:601-8.

2. Nielsen ML, Jensen SL. Malmstrem J. Gastrin and gastric acid secretion in hepaticojejunostomy Roux-en-Y. Surg Gynecol Obstet 1980;150:61-4.

3. Wheeler ES, Longmire WP Jr. Repair of benign stricture of the common bile duct by jejunal interposition choledochoduo- denostomy. Surg Gynecol Obstet 1978;146:260-2.

4. Grassi G, Broglia S, Dell’Osso A. Hepaticojejunoduodenoplasty in reoperation of the bile ducts. In: Grassi G, D’Onofrio G, eds. Digestive surgery. Proceedings of the First World Congress of Collegium lnternationale Chirurgiae Digestivae, Padova, Italy: Piccin Medical Books, 1973.

5. Sekine T, Tsukui H, Kameyama J, Sasaki I, Sato T. Influence of biliary diversion upon gastric secretion. Tohoku J Exp Med 1981;134:125-39.

6. Konturek SJ, Thor P. Effect of diversion and replacement of bile on pancreatic secretion. Dig Dis 1973;18:971-7.

7. Orloff MJ, Guillemin RCL, Nakaji NT. Isolation of the hormone responsible for the intestinal phase of gastric secretion. Gastroenterology 1977;72:820.

8. Santillana M, Wise L, Schuck M. Ballinger WF II. Changes in gastric acid secretion following resection or exclusion of different segments of the small intestine. Surgery 1969; 65~777-82.

9. Thomas FB, Shook DF, O’Dorisio TM, et al. Localization of gastric inhibitory polypeptide release by intestinal glucose perfusion in man. Gastroenterology 1977;72:49-54.

10. Yamagishi T, Debas HT. Gastric inhibitory polypeptide (GIP) is not the primary mediator of the enterogastrone action of fat in the dog. Gastroenterology 1980;78:931-6.

11. Ebeid AM, ESCOUKOU J, Fischer JE. Vasoactive intestinal peptide inhibition of stimulated gastric secretion. I. Inhibition of meat-stimulated gastric secretion. Am J Surg 1980;139: 817-23.

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