Effect of Gastric Bypass on Gastric Secretion Edward E. Mason, MD, Iowa City, Iowa James Ft. Munns, MD, Iowa City, Iowa Gerald P. Kealey, MD, Iowa City, Iowa
Roger Wangler, Iowa City, Iowa William Ft. Clarke, Iowa City, Iowa H. F. Cheng, PhD, Iowa City, Iowa Kenneth J. Printen, MD, Iowa City, Iowa
Subtotal gastrectomy was abandoned for the treatment of acid peptic disease because patients had difficulty in maintaining their body weight; the operation produced an intake deficiency. Gastric bypass is a reversible operation patterned after subtotal gastric resection and designed to produce weight loss in grossly obese people by restricting their food intake. It has been used in 377 patients at the University of Iowa during the last nine years and is an effective treatment for intractable obesity in the majority of such patients [I-3]. When gastric bypass was first considered for use in the treatment of obesity it was recognized that exclusion operations had been abandoned early in the history of gastric surgery because of the high incidence of stoma1 ulceration. Because gastric bypass excludes a large portion of the acid-secreting gastric mucosa with the antrum, thus preserving the normal gastric and duodenal relationships and mechanisms for control of acid secretion, it was predicted that stoma1 ulcers would be infrequent. Experiments performed in pouch dogs prior to the use of this operation in patients showed that gastric bypass produced a marked but not complete suppression of acid secretion in response to a meal [4]. When acid-secreting mucosa was removed, leaving the animals with an antral exclusion, an appreciable late intestinal phase of acid secretion followed feeding. When the antrum was then removed, the secretory response to a meal
From the Department of Surgery, University and Veterans Administration Hospitals; University of Iowa. Iowa City, Iowa. This work was supported in part by grant RR59 from the General Clinical Research Center Program of the Division of Research Resources, National Institutes of Health. Reprint requests should be addressed to Edward E. Mason, MD, Department of Surgery, University Hospitals, University of Iowa, Iowa City, Iowa 52242. Presented at the Sixteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Antonio, Texas, May 20-21. 1975.
was nearly abolished. Gastric bypass allowed some acid secretion in response to a meal but the acid secretory curves were low, flat, and similar to the curves observed after gastric resection in these same animals. Supported by data from animal experiments we used gastric bypass in two distinctly different groups of patients: those whose extreme obesity required a restriction in food intake and those with severe acid peptic disease. It soon became apparent that, in most patients with acid peptic disease, continued acidification of the antrum and duodenum would not inhibit acid secretion. Six of the eight patients studied required further treatment for stoma1 ulceration. One thin patient and one very obese patient, both with severe ulcer disease, have remained completely free of symptoms for more than five years after gastric bypass. Unfortunately, we cannot identify such patients in advance and therefore gastric bypass has been abandoned for treatment of acid peptic disease regardless of body weight. We have continued to study the effect of gastric bypass on acid secretion in morbidly obese patients without acid peptic disease. This paper ieviews pertinent observations in some of these patients. Material and Methods
There are essentially four types of observaiions that have provided information about gastric acid secretion in patients after gastric bypass: (1) indwelling pH; (2) standard analyses of gastric juice obtained from the excluded distal stomach; (3) serum gastrin determinations obtained preoperatively and postoperatively before and after a standard meal; and (4) the incidence of stoma1 ulceration in patients who have undergone gastric bypass. Indwelling pH was determined by the use of a long electrode which was passed into the stomach through
The American Journal of Surgery
Gastric Secretion the nose and positioned just below the cardia with fluoroscopic control. The electrode was attached to a pH meter and recorder. Two additional tubes were introduced simultaneously: one, saturated with potassium chloride, to serve as an indifferent electrode and another for aspirating the stomach at intervals during the recording. After a 1 hour period of recording the fasting pH, provided that the pH remained above 3, the patient was given Histalog@, 50 mg, and the recording was continued for a second hour. Distal pouch secretions were obtained via a gastrostomy tube, which one of the authors (KJP) uses to decompress the excluded 4stomach. (Figure 1.) Fourteen patients were studied during their early convalescence by aspirating gastric juice serially for 4 hours, first with a period of fasting followed by a standard meal and then on another day fasting followed by the administration of Histalog, 50 mg. The gastrin resonses of eight patients were studied before and four months after gastric bypass by administration of 250 ml of skim milk and radioimmunoassay of serum gastrin at 15 minute intervals for 90 minutes [5]. All patients have been followed closely by history and physical examination. Radiologic and endoscopic studies were used when indicated.
Results Serial indwelling pH studies were available in twenty-eight patients treated for obesity with gastric bypass. (Table I.) Twelve patients had a low fasting pH before and after gastric bypass, and stomal ulceration developed in two of these patients. Seven patients had a high fasting pH before and after gastric bypass but the pH dropped to a low level after Histalog stimulation before and after the operation. Eight patients had a high fasting pH after gastric bypass, remaining high after Histalog stimulation even though the pH had been low before gastric bypass. One patient had a low pH both before gastric bypass and during the early period after operation. The patient had achlorhydria in response to Histalog at a time when there were symptoms and signs of peripheral neuropathy and multiple vitamin deficiencies. On vitamin administration and closer supervision of her diet, the patient responded with a return of acid secretion and a disappearance of the peripheral neuropathy. The nine patients treated for acid peptic disease demonstrated an indwelling pH in the same low range as observed in many of the obese patients who did not develop ulcers. Results of the gastric aspiration studies from the distal pouch show a decrease in gastric acid secretion in comparison with collections from the en-
Volume 131, Febnmy I976
Figura 1. A tamporary geatmattnny was pked in tha ex&dad atomach and was used &wtng the earlypoatoperathfe period to detetmfne acid secretoryreqonae durhg fasting, to a meal, and after Hiatabg sthmbthm.
tire stomach obtained preoperatively; however, the pH remains well within the acid range. (Figure 2.) Part of this decrease is of course due to the smaller parietal cell mass since not all of the stomach has been excluded. The response after a meal was only one-fifth to one-fourth that observed after Histalog stimulation, which indicates that the fasting and meal-stimulated response is less than maximal for the excluded stomach. (Figure 3.) In analysis of the serum gastrin data, we elected to use orthogonal polynomials and separate quadratic curves that were fitted to the preoperative and postoperative data. The eight preoperative and eight postoperative curves were compared by multivariate analysis of variance. A computer program MANOVA provided the following equations: preoperative y(t) = 16.3839 + 3.1057g - 0.0313t2; postoperative y(t) = 14.6223 + 0.6976t - 0.0072t2. TABLE Number of Patients Showing Pattern 12
7 8 1
I Patterns of pH after Gastric Bypass After Histalog Stimulation
Fasting pH Before Operation
After Operation
After Operation
Low High Low Low
Low* High High High?
No Histalog Decreased High High?
*Stoma1 ulcer developed in 2 of these patients. TTemporary achlorhydria; after vitamin therapy, secretion returned.
acid
163
Mason et al
2.4
0 0
1
pti
2.0 c&5
0
pH= I. 92 ------------
-Al
pH=l.88
Prandial
Prandial
FIgwe 2. Mean pH in excluded stomach during fasting and after a meal.
Plots of these curves are given in Figure 4. Statistical comparison of the curves yields an exact F which is 4.63 with 3O and 5’ of freedom (p < 0.062). Individual comparisons of the mean, linear, and quadratic components of the curves yields the following: F(1,7); mean, 7.501 (p < 0.028); linear, 2.211 (p < 0.179); quadratic, 8.810 (p < 0.020). Overall comparison of preoperative to postoperative curves yields an F which’is nearly significant at the 5 per cent level. When the small size of the sample is considered, this result should still be interpreted as indicating a difference. Taken in light of the significant differences between mean responses and between quadratic terms, there seems m
6.4 2
5.6
P 2
4.8
\ e
4.0
3 ~
3.2
G 9
2.4
Prr Operation,
Histaloq Stimulation
Disial Pouch, Post Operation Hisialog Stlmutation DIrtal Pouch, Post Operal~on, Prandlol Stimulation
? 1.6 ho 0.8 0
Basal Secretion (1 hour)
15
30 TIME
60 (min
Figure 3. Postoperaflve acid secretion from the excluded stomach compared w/th the entire stomach studied preoperatively (HLsta/og dosage, 50 mg intramuscularly preand postoperative/y).
164
to be ample evidence that the operation does change the response mechanism. The overall average response is shifted downward considerably after the operation and the peakedness of the response is strikingly altered. It should also be noted here that even though the eight patients yield enough information to give statistical evidence of a change in the process, the estimated curves that were obtained from the analysis are of little predictive value. Many more subjects would be necessary if good estimates of the actual response curves and the variability between patients were to be obtained. The final test of whether gastric bypass is ulcerogenic depends on the incidence of stoma1 ulceration in patients who have had the operation. Between 1966 and May 6, 1975, 377 patients underwent gastric bypass as their primary operation for the control of obesity. In addition, sixteen patients who initially had gastroplasty underwent a second operation in which the gastroplasty was converted to gastric bypass. (Figure 5.) Seven stoma1 ulcers were observed in this group of patients, a 1.8 per cent incidence of ulcers in terms of patients and an incidence of one ulcer per 140 patient years at risk. Comments
Signs and symptoms of stoma1 ulcer, when they occurred, appeared two to sixty months after gastric bypass. Bleeding was almost always evident, usually as tarry stools but occasionally as coffee ground emesis. In most patients the bleeding was slow enough so that transfusions were not necessary. A decrease in hematocrit or hemoglobin should be considered with the suspicion that stoma1 ulceration may be present. This was the only sign in some patients. Of the seven patients in whom stoma1 ulceration did develop, one patient had a long afferent loop because of an improperly constructed antecolic gastroenterostomy. This patient was one of four patients not having a short loop retrocolic gastroenterostomy. She was treated by vagotomy and a shortening of the afferent loop with a retrocolic anastomosis and has been followed for twelve months without evidence of recurrence. Two patients were treated by vagotomy and resection of a portion of the fundic pouch. One of these patients died in the postoperative period secondary to a leak in the excluded stomach where it had been attached to the fundic pouch. A stoma1 ulcer in this patient developed after revision of her gastric bypass in an attempt to increase the weight loss. Two patients had their stomachs restored to
The American Journal
of Surgery
Gastric Secretion
normal continuity along with the addition of vagotomy. Two patients were treated medically and one of these has been followed for sixty months without evidence of recurrence of the stomal ulcer. The other patient became anemic seven months after gastric bypass. He was treated medically and at first seemed to respond. But he became anemic again at twenty-one months and thus underwent a resection of the excluded stomach and part of the fundic pouch. This patient’s excluded stomach was smaller and the fundic segment larger than any other patient we have followed. He also had excessive fasting acid secretion both before and early after gastric bypass. After removal of the nasogastric tube his fundic pouch became overdistended and perforated. Emergency truncal vagotomy and closure of the perforation were performed. Before his last operation, for the stoma1 ulcer, the patient’s fasting serum gastrin level was 45 units/ml, which is well within the normal range but greater than we usually see after gastric bypass. The upper pouch prior to the last operation still produced an amount of acid under fasting conditions that would be excessive for an entire stomach. It can be concluded, therefore, that this patient had a preexisting potential for acid peptic disease. Also, transection of stomach was much too low, so that the antrum was inadequately suppressed and the parietal cell mass above the stoma was excessive. There are at least two major concerns in this study: (1) the usual effect of gastric bypass on gastric acid secretion in humans and (2) the reason for the excessive acid secretion of some people in response to gastric bypass, which leads to stoma1 ulceration. Our conclusions can be summarized as follows: (1) gastric bypass decreases gastric acid secretion in most people and (2) the majority of obese patients have their gastric acid secretion under antral control, which gives them a favorable
Y(t) = 163839
‘f(t) =14 Mean
f
I
Oo
I
5223
+ 3 1057t
- 00313t*
+ 06976t
- 00072t*
k S 3
I
I
I
I
I1
10
11
30 45 60 75 15 Minutes After ‘250ml Skim Milk
I
90
Figure 4. Two quadratk curves whkh were derived from the data cot&ted pre- and pastoperatIve& from emt patients. The mean f standard devlatkn Rs plotted against minutes In reiatknship to admlnktratkn of 250 ml of skim milk.
response to gastric bypass. However, it seems that acid secretion is predominantly under vagal control in a few obese patients and in most of those patients with acid peptic disease. The latter patients have a poor response to gastric bypass insofar as regulation of acid secretion is concerned. The regulatory effect of the antrum on acid secretion is the chief concern of surgeons who consider performing any exclusion operation. Our original experiments on pouch secretion demon-
Figvre 5. Gasfmplastywas convert-’ ed to gas&k bypass in 16 patients. Gas&k bypass was the prhnary procedure in 373 patients.
Vohma
131, February 1676
165
Mason et al
TWO- THIRDS 4’
GASTRK
BYPASS
-;
Y3 GASTRK
UESfC’lirOhi
Figure 6. Changes that were observed in Pavlov pouch acid secretion after a standard meal when gastric bypass is performed, when acid secreting mucosa Is removed from the excluded stomach, and when the antrum is then removed. (From Mason EE, /to CC: Surg Clln NorthAm 47: 1345, 1967, w/th permission of the pubW?er.)
&rated the marked difference in acid secretory response between exclusion of acid mucosa with the antrum and exclusion of the antrum alone [4]. (Figure 6.) The effect was a difference between antral suppression and uninhibited antral function. The course of most of the patients who have undergone gastric bypass for obesity and the data presented from these studies demonstrate that acid secretion is decreased after gastric bypass. In some patients there even appears to be atrophy of the parietal cell mass since the fundic pH remains high after Histalog stimulation. The serum gastrin levels show a significant decrease in mean response to a standard feeding. Most obese and apparently even a few patients with acid peptic disease follow this response of decreased postprandial acid secretion and a diminished gastrin response after gastric bypass. Ingested food stimulates a mild acid secretion and any further gastric or intestinal phase of secretion is inhibited by the acid in the antrum. Gastric bypass causes the food, which normally would produce chemical and mechanical stimulation of the antrum, to bypass the distal stomach. In this way the operation produces both an increase in inhibition and a decrease in stimulation of acid secretion. If antacids are used, they will not reach the
166
antral area so that antral inhibition by acid continues to be in effect. Fortunately, stoma1 ulceration is uncommon in the obese patient after extensive gastric exclusion. We have only eight patients with duodenal ulcer who were subjected to an estimated 70 per cent gastric exclusion. We hoped that the more extensive exclusion would accomplish satisfactory control of excessive acid secretion even though earlier studies of a 50 per cent gastric exclusion failed to control peptic ulcer disease in the hands of Kay [6,7]. Gastric bypass is not an adequate operative procedure for those patients who have acid peptic disease, regardless of their body weight. The addition of vagotomy as practiced by Waddell and Bartlett [8] may provide a more satisfactory treatment. However, we recommend more conventional treatment, that is, subtotal gastric resection, for those patients who require treatment of both ulcer disease and obesity. One of our patients had excessive secretion of acid during the early days after gastric bypass and because of the large volume of secretion together with inadequate function of the nasogastric tube and obstruction of the stoma, there was a perforation of the stomach that required emergency operation. In addition to closure of the perforation, truncal vagotomy was per-
The Amerkan Journalol Surgery
Gastric Secretion
formed, and we have pathologic evidence that at least two vagal trunks were divided. Despite this procedure, which is similar to that used by Waddell and Bartlett [8] for the treatment of acid peptic disease, this patient developed a stoma1 ulcer. The best measure for prevention of stoma1 ulcer when employing gastric bypass is to leave a very small fundic segment. This also produces the best weight loss. In addition, there is maximal acidification of the antrum from any acid that is secreted. For those obese patients who have had gastric bypass and in whom stoma1 ulceration develops at a later time, there are several choices of treatment, depending on the severity of disease. Antacid therapy may be effective if the disease is mild or becomes evident late after gastric bypass. The antacid neutralizes the acid secreted in the fundic pouch but does not neutralize the acid secreted in the excluded stomach. In contrast to antacid therapy in the patient with an intact stomach, there is no interference of the antacid with the inhibitory effect of secreted acid on antrum and duodenum. However, just as it is known that the antrum is less effective in controlling acid secretion in patients with duodenal ulcer as a primary disease, so it appears that the antrum is of less importance in the obese patient in whom a stoma1 ulcer develops. If the ulcer does not respond to conservative treatment, then a combination of vagotomy, resection of the excluded stomach, and revision of the gastroenterostomy is the procedure most certain to obviate further operative treatment. We have not found any method to detect those obese patients who might be predisposed to the development of stoma1 ulcer, through studies which might be performed either before or after gastric bypass. Indwelling pH and standard acid secretory tests, performed with an indwelling nasogastric tube or through a gastrostomy, and serum gastrin response to a standard meal have provided us with data which support the thesis that in most patients gastric bypass decreases gastric acid secretion. None of these tests, however, are adequate for the prognostic and diagnostic study of a specific patient. Finally, the incidence of stoma1 ulcer in patients undergoing gastric bypass is at the present time 1.8 per cent, which would seem to be within the range of ulcer production in the population at large. There may be some morbidly obese patients with an unrecognized predisposition to the development of ulcer who suppress the ulceration by frequent eating. The earliest manifestation of this
Vohme 131, February 1976
may be an unusual volume of acid secretion after gastric bypass, which if unrecognized and improperly managed may lead to overdistension of the small fundic pouch and perforation, as occurred in the patient mentioned above. Our present emphasis on a small fundic pouch and a somewhat larger diameter (12 mm Hegar) gastroenterostomy stoma should greatly reduce the risk of this serious complication. We see occasional patients with known duodenal ulcer who are excessively obese because of the large amounts of milk, cream, and other foods used as part of their medical management. If we could identify the obese patient at high risk for stoma1 ulcer, a subtotal gastric resection with gastroenterostomy of 12 mm diameter would accomplish the same effect as subtotal gastric bypass and probably with less risk of stoma1 ulceration.
Gastric bypass as a 90 per cent gastric exclusion operation was used in 393 patients with massive obesity to limit food intake. Stoma1 ulcer has occurred in 1.8 per cent of such patients or one ulcer per 140 man years of observation. The studies of indwelling fundic pH and of gastric acid secretion from the excluded stomach indicate that acid secretion is reduced after gastric bypass but that the acid, unbuffered by food in the excluded stomach, results in a lowered gastrin secretion after a meal. Thus, gastric bypass in inhibitory to acid secretion in most morbidly obese patients who do not have known acid peptic disease. References 1. Mason EE, Ito C: Gastric bypass. Ann Surg 170: 329, 1969. 2. Printen KJ, Mason EE: Gastric surgery for relief of morbid obesity. Arch Surg 106: 428. 1973. 3. Soper RT, Mason EE. Printen KJ, Zellweger H: Gastric bypass for morbid obesity in children and adolescents. J Pediafr Surg 10: 51, 1975. 4. Mason EE. lto C: Gastric bypass in obesity. Surg C/in North Am47: 1345. 1967. 5. Yalow RS. Berson Sk Radioimmunoassay of gestrin. &M-oenferology 58: 1, 1970. 6. Kay AW: Hemigastric exclusion in the treatment of duodenal ulcer. JR Colt Surg Edinb 2: 54, 1957. 7. Kay AW: The pyloric antrum and peptic ulceration. Qstroenterologie 89: 282. 1958. 8. Waddell WR, Bartlett MK: Antral exclusion with vagotomyfor duodenal ulcer. I. Acid-secretory studies on 50 patients. Ann Surg 146: 3, 1957.
Discussion David L. Nahrwold (Hershey, PA): The meal was obviously ingested orally before the bypass, but after the bypass, was it put in through the tube or ingested
167
Mason et al orally? In addition, out the bypass the bly totally vagally this could account
I wonder if in the process of carrying stomach is at least partially or possidenervated. It would seem to me that for all the results you have presented.
Edward E. Mason (closing): Doctor Nahrwold, the meal ingested was 250 cc of skim milk given by mouth the same way both pre- and postoperatively. With regard to vagal denervation, this is something that we should have done but did not consider soon enough. We are doing it now in terms of studying Hollander tests postoperatively through the gastrostomy tube in the excluded stomach. However, our original concern was whether stoma1 ulcers developed in these patients. Although it is very interesting to know whether the decrease in gastrin is due to vagotomy or whether it is simply due to other reasons, it nevertheless remains that the likelihood of stoma1 ulcer would seem to be small.
168
With regard to side effects, as we originally performed this procedure, we made a rather large gastroenterostomy and about one third of the patients did have dumping symptoms. We made the stoma so small that we prolonged delay in getting the patients to open up and getting them out of the hospital. We have backed off now and we are making the stoma 12 mm in diameter, using a Hegar dilator for calibration. With this small stoma, the incidence of dumping is very low. With regard to weight loss, within a year these patients decrease from 142 kilograms to 107 kilograms. We are now making a smaller fundic pouch. If the transection is too low, there is too much parietal cell mass above the stoma, which will increase the amount of acid washing over the area and increase the risk of stoma1 ulceration. Also, if the transection is too low, there is too little parietal cell mass below the site of transection, with inadequate inhibition of the antrum and again an increased risk of stomach ulceration.
The American Journal
of Surgery
Roger Wangler, Iowa City, Iowa William Ft. Clarke, Iowa City, Iowa H. F. Cheng, PhD, Iowa City, Iowa Kenneth J. Printen, MD, Iowa City, Iowa
Subtotal gastrectomy was abandoned for the treatment of acid peptic disease because patients had difficulty in maintaining their body weight; the operation produced an intake deficiency. Gastric bypass is a reversible operation patterned after subtotal gastric resection and designed to produce weight loss in grossly obese people by restricting their food intake. It has been used in 377 patients at the University of Iowa during the last nine years and is an effective treatment for intractable obesity in the majority of such patients [I-3]. When gastric bypass was first considered for use in the treatment of obesity it was recognized that exclusion operations had been abandoned early in the history of gastric surgery because of the high incidence of stoma1 ulceration. Because gastric bypass excludes a large portion of the acid-secreting gastric mucosa with the antrum, thus preserving the normal gastric and duodenal relationships and mechanisms for control of acid secretion, it was predicted that stoma1 ulcers would be infrequent. Experiments performed in pouch dogs prior to the use of this operation in patients showed that gastric bypass produced a marked but not complete suppression of acid secretion in response to a meal [4]. When acid-secreting mucosa was removed, leaving the animals with an antral exclusion, an appreciable late intestinal phase of acid secretion followed feeding. When the antrum was then removed, the secretory response to a meal
From the Department of Surgery, University and Veterans Administration Hospitals; University of Iowa. Iowa City, Iowa. This work was supported in part by grant RR59 from the General Clinical Research Center Program of the Division of Research Resources, National Institutes of Health. Reprint requests should be addressed to Edward E. Mason, MD, Department of Surgery, University Hospitals, University of Iowa, Iowa City, Iowa 52242. Presented at the Sixteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Antonio, Texas, May 20-21. 1975.
was nearly abolished. Gastric bypass allowed some acid secretion in response to a meal but the acid secretory curves were low, flat, and similar to the curves observed after gastric resection in these same animals. Supported by data from animal experiments we used gastric bypass in two distinctly different groups of patients: those whose extreme obesity required a restriction in food intake and those with severe acid peptic disease. It soon became apparent that, in most patients with acid peptic disease, continued acidification of the antrum and duodenum would not inhibit acid secretion. Six of the eight patients studied required further treatment for stoma1 ulceration. One thin patient and one very obese patient, both with severe ulcer disease, have remained completely free of symptoms for more than five years after gastric bypass. Unfortunately, we cannot identify such patients in advance and therefore gastric bypass has been abandoned for treatment of acid peptic disease regardless of body weight. We have continued to study the effect of gastric bypass on acid secretion in morbidly obese patients without acid peptic disease. This paper ieviews pertinent observations in some of these patients. Material and Methods
There are essentially four types of observaiions that have provided information about gastric acid secretion in patients after gastric bypass: (1) indwelling pH; (2) standard analyses of gastric juice obtained from the excluded distal stomach; (3) serum gastrin determinations obtained preoperatively and postoperatively before and after a standard meal; and (4) the incidence of stoma1 ulceration in patients who have undergone gastric bypass. Indwelling pH was determined by the use of a long electrode which was passed into the stomach through
The American Journal of Surgery
Gastric Secretion the nose and positioned just below the cardia with fluoroscopic control. The electrode was attached to a pH meter and recorder. Two additional tubes were introduced simultaneously: one, saturated with potassium chloride, to serve as an indifferent electrode and another for aspirating the stomach at intervals during the recording. After a 1 hour period of recording the fasting pH, provided that the pH remained above 3, the patient was given Histalog@, 50 mg, and the recording was continued for a second hour. Distal pouch secretions were obtained via a gastrostomy tube, which one of the authors (KJP) uses to decompress the excluded 4stomach. (Figure 1.) Fourteen patients were studied during their early convalescence by aspirating gastric juice serially for 4 hours, first with a period of fasting followed by a standard meal and then on another day fasting followed by the administration of Histalog, 50 mg. The gastrin resonses of eight patients were studied before and four months after gastric bypass by administration of 250 ml of skim milk and radioimmunoassay of serum gastrin at 15 minute intervals for 90 minutes [5]. All patients have been followed closely by history and physical examination. Radiologic and endoscopic studies were used when indicated.
Results Serial indwelling pH studies were available in twenty-eight patients treated for obesity with gastric bypass. (Table I.) Twelve patients had a low fasting pH before and after gastric bypass, and stomal ulceration developed in two of these patients. Seven patients had a high fasting pH before and after gastric bypass but the pH dropped to a low level after Histalog stimulation before and after the operation. Eight patients had a high fasting pH after gastric bypass, remaining high after Histalog stimulation even though the pH had been low before gastric bypass. One patient had a low pH both before gastric bypass and during the early period after operation. The patient had achlorhydria in response to Histalog at a time when there were symptoms and signs of peripheral neuropathy and multiple vitamin deficiencies. On vitamin administration and closer supervision of her diet, the patient responded with a return of acid secretion and a disappearance of the peripheral neuropathy. The nine patients treated for acid peptic disease demonstrated an indwelling pH in the same low range as observed in many of the obese patients who did not develop ulcers. Results of the gastric aspiration studies from the distal pouch show a decrease in gastric acid secretion in comparison with collections from the en-
Volume 131, Febnmy I976
Figura 1. A tamporary geatmattnny was pked in tha ex&dad atomach and was used &wtng the earlypoatoperathfe period to detetmfne acid secretoryreqonae durhg fasting, to a meal, and after Hiatabg sthmbthm.
tire stomach obtained preoperatively; however, the pH remains well within the acid range. (Figure 2.) Part of this decrease is of course due to the smaller parietal cell mass since not all of the stomach has been excluded. The response after a meal was only one-fifth to one-fourth that observed after Histalog stimulation, which indicates that the fasting and meal-stimulated response is less than maximal for the excluded stomach. (Figure 3.) In analysis of the serum gastrin data, we elected to use orthogonal polynomials and separate quadratic curves that were fitted to the preoperative and postoperative data. The eight preoperative and eight postoperative curves were compared by multivariate analysis of variance. A computer program MANOVA provided the following equations: preoperative y(t) = 16.3839 + 3.1057g - 0.0313t2; postoperative y(t) = 14.6223 + 0.6976t - 0.0072t2. TABLE Number of Patients Showing Pattern 12
7 8 1
I Patterns of pH after Gastric Bypass After Histalog Stimulation
Fasting pH Before Operation
After Operation
After Operation
Low High Low Low
Low* High High High?
No Histalog Decreased High High?
*Stoma1 ulcer developed in 2 of these patients. TTemporary achlorhydria; after vitamin therapy, secretion returned.
acid
163
Mason et al
2.4
0 0
1
pti
2.0 c&5
0
pH= I. 92 ------------
-Al
pH=l.88
Prandial
Prandial
FIgwe 2. Mean pH in excluded stomach during fasting and after a meal.
Plots of these curves are given in Figure 4. Statistical comparison of the curves yields an exact F which is 4.63 with 3O and 5’ of freedom (p < 0.062). Individual comparisons of the mean, linear, and quadratic components of the curves yields the following: F(1,7); mean, 7.501 (p < 0.028); linear, 2.211 (p < 0.179); quadratic, 8.810 (p < 0.020). Overall comparison of preoperative to postoperative curves yields an F which’is nearly significant at the 5 per cent level. When the small size of the sample is considered, this result should still be interpreted as indicating a difference. Taken in light of the significant differences between mean responses and between quadratic terms, there seems m
6.4 2
5.6
P 2
4.8
\ e
4.0
3 ~
3.2
G 9
2.4
Prr Operation,
Histaloq Stimulation
Disial Pouch, Post Operation Hisialog Stlmutation DIrtal Pouch, Post Operal~on, Prandlol Stimulation
? 1.6 ho 0.8 0
Basal Secretion (1 hour)
15
30 TIME
60 (min
Figure 3. Postoperaflve acid secretion from the excluded stomach compared w/th the entire stomach studied preoperatively (HLsta/og dosage, 50 mg intramuscularly preand postoperative/y).
164
to be ample evidence that the operation does change the response mechanism. The overall average response is shifted downward considerably after the operation and the peakedness of the response is strikingly altered. It should also be noted here that even though the eight patients yield enough information to give statistical evidence of a change in the process, the estimated curves that were obtained from the analysis are of little predictive value. Many more subjects would be necessary if good estimates of the actual response curves and the variability between patients were to be obtained. The final test of whether gastric bypass is ulcerogenic depends on the incidence of stoma1 ulceration in patients who have had the operation. Between 1966 and May 6, 1975, 377 patients underwent gastric bypass as their primary operation for the control of obesity. In addition, sixteen patients who initially had gastroplasty underwent a second operation in which the gastroplasty was converted to gastric bypass. (Figure 5.) Seven stoma1 ulcers were observed in this group of patients, a 1.8 per cent incidence of ulcers in terms of patients and an incidence of one ulcer per 140 patient years at risk. Comments
Signs and symptoms of stoma1 ulcer, when they occurred, appeared two to sixty months after gastric bypass. Bleeding was almost always evident, usually as tarry stools but occasionally as coffee ground emesis. In most patients the bleeding was slow enough so that transfusions were not necessary. A decrease in hematocrit or hemoglobin should be considered with the suspicion that stoma1 ulceration may be present. This was the only sign in some patients. Of the seven patients in whom stoma1 ulceration did develop, one patient had a long afferent loop because of an improperly constructed antecolic gastroenterostomy. This patient was one of four patients not having a short loop retrocolic gastroenterostomy. She was treated by vagotomy and a shortening of the afferent loop with a retrocolic anastomosis and has been followed for twelve months without evidence of recurrence. Two patients were treated by vagotomy and resection of a portion of the fundic pouch. One of these patients died in the postoperative period secondary to a leak in the excluded stomach where it had been attached to the fundic pouch. A stoma1 ulcer in this patient developed after revision of her gastric bypass in an attempt to increase the weight loss. Two patients had their stomachs restored to
The American Journal
of Surgery
Gastric Secretion
normal continuity along with the addition of vagotomy. Two patients were treated medically and one of these has been followed for sixty months without evidence of recurrence of the stomal ulcer. The other patient became anemic seven months after gastric bypass. He was treated medically and at first seemed to respond. But he became anemic again at twenty-one months and thus underwent a resection of the excluded stomach and part of the fundic pouch. This patient’s excluded stomach was smaller and the fundic segment larger than any other patient we have followed. He also had excessive fasting acid secretion both before and early after gastric bypass. After removal of the nasogastric tube his fundic pouch became overdistended and perforated. Emergency truncal vagotomy and closure of the perforation were performed. Before his last operation, for the stoma1 ulcer, the patient’s fasting serum gastrin level was 45 units/ml, which is well within the normal range but greater than we usually see after gastric bypass. The upper pouch prior to the last operation still produced an amount of acid under fasting conditions that would be excessive for an entire stomach. It can be concluded, therefore, that this patient had a preexisting potential for acid peptic disease. Also, transection of stomach was much too low, so that the antrum was inadequately suppressed and the parietal cell mass above the stoma was excessive. There are at least two major concerns in this study: (1) the usual effect of gastric bypass on gastric acid secretion in humans and (2) the reason for the excessive acid secretion of some people in response to gastric bypass, which leads to stoma1 ulceration. Our conclusions can be summarized as follows: (1) gastric bypass decreases gastric acid secretion in most people and (2) the majority of obese patients have their gastric acid secretion under antral control, which gives them a favorable
Y(t) = 163839
‘f(t) =14 Mean
f
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Oo
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5223
+ 3 1057t
- 00313t*
+ 06976t
- 00072t*
k S 3
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I
I
I
I1
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11
30 45 60 75 15 Minutes After ‘250ml Skim Milk
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Figure 4. Two quadratk curves whkh were derived from the data cot&ted pre- and pastoperatIve& from emt patients. The mean f standard devlatkn Rs plotted against minutes In reiatknship to admlnktratkn of 250 ml of skim milk.
response to gastric bypass. However, it seems that acid secretion is predominantly under vagal control in a few obese patients and in most of those patients with acid peptic disease. The latter patients have a poor response to gastric bypass insofar as regulation of acid secretion is concerned. The regulatory effect of the antrum on acid secretion is the chief concern of surgeons who consider performing any exclusion operation. Our original experiments on pouch secretion demon-
Figvre 5. Gasfmplastywas convert-’ ed to gas&k bypass in 16 patients. Gas&k bypass was the prhnary procedure in 373 patients.
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131, February 1676
165
Mason et al
TWO- THIRDS 4’
GASTRK
BYPASS
-;
Y3 GASTRK
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Figure 6. Changes that were observed in Pavlov pouch acid secretion after a standard meal when gastric bypass is performed, when acid secreting mucosa Is removed from the excluded stomach, and when the antrum is then removed. (From Mason EE, /to CC: Surg Clln NorthAm 47: 1345, 1967, w/th permission of the pubW?er.)
&rated the marked difference in acid secretory response between exclusion of acid mucosa with the antrum and exclusion of the antrum alone [4]. (Figure 6.) The effect was a difference between antral suppression and uninhibited antral function. The course of most of the patients who have undergone gastric bypass for obesity and the data presented from these studies demonstrate that acid secretion is decreased after gastric bypass. In some patients there even appears to be atrophy of the parietal cell mass since the fundic pH remains high after Histalog stimulation. The serum gastrin levels show a significant decrease in mean response to a standard feeding. Most obese and apparently even a few patients with acid peptic disease follow this response of decreased postprandial acid secretion and a diminished gastrin response after gastric bypass. Ingested food stimulates a mild acid secretion and any further gastric or intestinal phase of secretion is inhibited by the acid in the antrum. Gastric bypass causes the food, which normally would produce chemical and mechanical stimulation of the antrum, to bypass the distal stomach. In this way the operation produces both an increase in inhibition and a decrease in stimulation of acid secretion. If antacids are used, they will not reach the
166
antral area so that antral inhibition by acid continues to be in effect. Fortunately, stoma1 ulceration is uncommon in the obese patient after extensive gastric exclusion. We have only eight patients with duodenal ulcer who were subjected to an estimated 70 per cent gastric exclusion. We hoped that the more extensive exclusion would accomplish satisfactory control of excessive acid secretion even though earlier studies of a 50 per cent gastric exclusion failed to control peptic ulcer disease in the hands of Kay [6,7]. Gastric bypass is not an adequate operative procedure for those patients who have acid peptic disease, regardless of their body weight. The addition of vagotomy as practiced by Waddell and Bartlett [8] may provide a more satisfactory treatment. However, we recommend more conventional treatment, that is, subtotal gastric resection, for those patients who require treatment of both ulcer disease and obesity. One of our patients had excessive secretion of acid during the early days after gastric bypass and because of the large volume of secretion together with inadequate function of the nasogastric tube and obstruction of the stoma, there was a perforation of the stomach that required emergency operation. In addition to closure of the perforation, truncal vagotomy was per-
The Amerkan Journalol Surgery
Gastric Secretion
formed, and we have pathologic evidence that at least two vagal trunks were divided. Despite this procedure, which is similar to that used by Waddell and Bartlett [8] for the treatment of acid peptic disease, this patient developed a stoma1 ulcer. The best measure for prevention of stoma1 ulcer when employing gastric bypass is to leave a very small fundic segment. This also produces the best weight loss. In addition, there is maximal acidification of the antrum from any acid that is secreted. For those obese patients who have had gastric bypass and in whom stoma1 ulceration develops at a later time, there are several choices of treatment, depending on the severity of disease. Antacid therapy may be effective if the disease is mild or becomes evident late after gastric bypass. The antacid neutralizes the acid secreted in the fundic pouch but does not neutralize the acid secreted in the excluded stomach. In contrast to antacid therapy in the patient with an intact stomach, there is no interference of the antacid with the inhibitory effect of secreted acid on antrum and duodenum. However, just as it is known that the antrum is less effective in controlling acid secretion in patients with duodenal ulcer as a primary disease, so it appears that the antrum is of less importance in the obese patient in whom a stoma1 ulcer develops. If the ulcer does not respond to conservative treatment, then a combination of vagotomy, resection of the excluded stomach, and revision of the gastroenterostomy is the procedure most certain to obviate further operative treatment. We have not found any method to detect those obese patients who might be predisposed to the development of stoma1 ulcer, through studies which might be performed either before or after gastric bypass. Indwelling pH and standard acid secretory tests, performed with an indwelling nasogastric tube or through a gastrostomy, and serum gastrin response to a standard meal have provided us with data which support the thesis that in most patients gastric bypass decreases gastric acid secretion. None of these tests, however, are adequate for the prognostic and diagnostic study of a specific patient. Finally, the incidence of stoma1 ulcer in patients undergoing gastric bypass is at the present time 1.8 per cent, which would seem to be within the range of ulcer production in the population at large. There may be some morbidly obese patients with an unrecognized predisposition to the development of ulcer who suppress the ulceration by frequent eating. The earliest manifestation of this
Vohme 131, February 1976
may be an unusual volume of acid secretion after gastric bypass, which if unrecognized and improperly managed may lead to overdistension of the small fundic pouch and perforation, as occurred in the patient mentioned above. Our present emphasis on a small fundic pouch and a somewhat larger diameter (12 mm Hegar) gastroenterostomy stoma should greatly reduce the risk of this serious complication. We see occasional patients with known duodenal ulcer who are excessively obese because of the large amounts of milk, cream, and other foods used as part of their medical management. If we could identify the obese patient at high risk for stoma1 ulcer, a subtotal gastric resection with gastroenterostomy of 12 mm diameter would accomplish the same effect as subtotal gastric bypass and probably with less risk of stoma1 ulceration.
Gastric bypass as a 90 per cent gastric exclusion operation was used in 393 patients with massive obesity to limit food intake. Stoma1 ulcer has occurred in 1.8 per cent of such patients or one ulcer per 140 man years of observation. The studies of indwelling fundic pH and of gastric acid secretion from the excluded stomach indicate that acid secretion is reduced after gastric bypass but that the acid, unbuffered by food in the excluded stomach, results in a lowered gastrin secretion after a meal. Thus, gastric bypass in inhibitory to acid secretion in most morbidly obese patients who do not have known acid peptic disease. References 1. Mason EE, Ito C: Gastric bypass. Ann Surg 170: 329, 1969. 2. Printen KJ, Mason EE: Gastric surgery for relief of morbid obesity. Arch Surg 106: 428. 1973. 3. Soper RT, Mason EE. Printen KJ, Zellweger H: Gastric bypass for morbid obesity in children and adolescents. J Pediafr Surg 10: 51, 1975. 4. Mason EE. lto C: Gastric bypass in obesity. Surg C/in North Am47: 1345. 1967. 5. Yalow RS. Berson Sk Radioimmunoassay of gestrin. &M-oenferology 58: 1, 1970. 6. Kay AW: Hemigastric exclusion in the treatment of duodenal ulcer. JR Colt Surg Edinb 2: 54, 1957. 7. Kay AW: The pyloric antrum and peptic ulceration. Qstroenterologie 89: 282. 1958. 8. Waddell WR, Bartlett MK: Antral exclusion with vagotomyfor duodenal ulcer. I. Acid-secretory studies on 50 patients. Ann Surg 146: 3, 1957.
Discussion David L. Nahrwold (Hershey, PA): The meal was obviously ingested orally before the bypass, but after the bypass, was it put in through the tube or ingested
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Mason et al orally? In addition, out the bypass the bly totally vagally this could account
I wonder if in the process of carrying stomach is at least partially or possidenervated. It would seem to me that for all the results you have presented.
Edward E. Mason (closing): Doctor Nahrwold, the meal ingested was 250 cc of skim milk given by mouth the same way both pre- and postoperatively. With regard to vagal denervation, this is something that we should have done but did not consider soon enough. We are doing it now in terms of studying Hollander tests postoperatively through the gastrostomy tube in the excluded stomach. However, our original concern was whether stoma1 ulcers developed in these patients. Although it is very interesting to know whether the decrease in gastrin is due to vagotomy or whether it is simply due to other reasons, it nevertheless remains that the likelihood of stoma1 ulcer would seem to be small.
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With regard to side effects, as we originally performed this procedure, we made a rather large gastroenterostomy and about one third of the patients did have dumping symptoms. We made the stoma so small that we prolonged delay in getting the patients to open up and getting them out of the hospital. We have backed off now and we are making the stoma 12 mm in diameter, using a Hegar dilator for calibration. With this small stoma, the incidence of dumping is very low. With regard to weight loss, within a year these patients decrease from 142 kilograms to 107 kilograms. We are now making a smaller fundic pouch. If the transection is too low, there is too much parietal cell mass above the stoma, which will increase the amount of acid washing over the area and increase the risk of stoma1 ulceration. Also, if the transection is too low, there is too little parietal cell mass below the site of transection, with inadequate inhibition of the antrum and again an increased risk of stomach ulceration.
The American Journal
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