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Antral function and recurrent ulceration
Antral
Function
and Recurrent
G. R. GILES, M.B., F.R.c.s., M. C. MASON,
Ulceration
B.SC.,B.M.,AND C. G. CLARK, M.D., CKM., F.R.C.S.,
Leeds, England
From the Department Leeds, England.
of
size 12 French
Surgery, University of Leeds,
gauge nasogastric tube, the resting contents of the stomach were discarded and basal secretions were obtained in fifteen minute collections over one hour using motor pump suction, interrupted at intervals with air insufflation to prevent blockage of the tube. Thereafter the following tests were performed : Histamine Stimulation. The procedure described by Lawrie, Smith, and Forrest [3] was used, with a continuous infusion of histamine acid phosphate at a dose of 0.04 mg./kg./hr. Secretions were collected in fifteen minute samples for one hour, and the secretory capacity of the stomach was calculated from the peak thirty minute output, and expressed as mEq. per fifteen minutes. Insulin Stimzclation. A procedure was used in which insulin was injected intravenously in a dose of 0.15 unit/kg. and secretions were collected for two hours. A positive response was recorded only when there was a rise both in acid concentration and output according to the criteria of Hollander [4], but we also noted whether the response was early (in the first hour) or late (in the second hour), as recommended by Ross and Kay [S]. Antral Stimulation. The technic described by Giles and Clark [6] was used in which a stable solution of meat extract, with pH adjusted to 7.0 by added bicarbonate, is introduced into the stomach and left for fifteen minutes before being completely aspirated. The secretions were collected over the next hour and the antral response was measured using the peak fifteen minute sample. All secretions were filtered through glass wool and a I ml. aliquot was used for titration with N/100 solid sodium hydroxide, using Topfer’s reagent as indicator. The results are expressed either as concentration in mEq./L. or as acid output in mEq. per
interest in the treatment of chronic duodenal ulceration by vagotomy and a gastric drainage procedure led us to examine the factors which might be concerned with recurrent ulceration. It is generally accepted that incomplete vagotomy is the major cause of recurrence, but it has been suggested [l] that in some cases even complete vagotomy will not always lower acid secretion sufficient to prevent further ulceration. In these patients it has been suggested [2] that the antrum may be capable of maintaining the acid output at a high level. We have therefore studied twenty-two patients with proved recurrent ulceration after vagotomy. The completeness of vagotomy was assessed by the insulin test, and the secretory capacity of the stomach was determined by histamine infusion. In addition we have used a simple test of antral function based on meat extract stimulation. The results of these studies have been compared with observations in thirty-six patients with duodenal ulceration examined before and after operation. ENEWED
R
MATERIAL AND METHODS
Of the twenty-two patients with recurrent ulceration after vagotomy and gastric drainage (nineteen had pyloroplasty and three gastroenterostomy) there were seventeen male and five female patients whose ages ranged from twenty-one to fifty-five years The control group consisted of thirty-six patients with chronic duodenal ulcer, thirty-one male and five female patients whose ages ranged from eighteen to sixty-eight years. These patients were treated by vagotomy and pyloroplasty, and in every case the vagotomy was judged complete by postoperative secretory studies. Gastric secretion studies were performed after a twelve hour overnight fast. After intubation with a
unit fifteen minutes. RESULTS
Insulin Stimulation Test. This test was performed on at least one occasion in each patient. In three patients with proved recurrent ulceration, a negative response was recorded, but 472
American Journal of Surgery
Antral Function and Recurrent Ulceration
473
TABLE I RESULTSOF HISTAMINEAND ANTRAL STIMULATIONTESTS
Patients With duodenal ulcer (preoperative test) With duodenal ulcer (postoperative test, insulin negative) With recurrent ulcer and early positive response to insulin With recurrent ulcer and late positive response to insulin
Basal Acid Secretion (mEq./l5 min.)
Acid after Histamine Stimulation (mEq./lS min.)
36
1.2 f
1.0 S.D.
9.2 f
36
0.3 f
0.3 SD.
3.8 + 2.1 S.D.
14
1.5 zt 0.9 SD.
7.6 f
3.2 SD.
0.2
3.6 f
2.3 S.D. i
No. of Patients
4.0 III 2.4
3.6 f 5
only after tests on two separate occasions. In the remaining nineteen patients with recurrent ulceration, there was a positive response which occurred in the first hour (early) in fourteen, and in the second hour (late) in five. This division of positive responses into early and late has been maintained in considering the results of other secretion studies. Basal Secretion. The effect of vagotomy on spontaneous basal secretion is shown in Table I. In thirty-six patients with duodenal ulcer the preoperative level was 1.2 f 1.0 mEq./l5 min. and after complete vagotomy this was reduced to 0.3 f 0.3 mEq./l5 min. with thirteen subjects rendered achlorhydric. In the nineteen subjects with recurrent ulceration and a positive insulin test, only one had achlorhydria, a patient who showed a late positive response to insulin. In the remainder the level of basal acid secretion appeared to be related to the type of response to insulin. When there was an early positive response, the basal secretion was 1.5 f 0.9 mEq./l5 min., which resembled the level in patients prior to operation. With a late positive response the basal acid was 0.2 mEq./l5 min., a value similar to that found in patients with complete vagotomy. Histamine-Stimulated Secretion. Table I shows the results of the histamine tests in thirty-six patients before and after complete vagotomy. The maximum acid output before operation ranged from 3.4 to 21.0 mEq./l5 min., with a mean of 9.2 f 3.2 mEq./l5 min. This was reduced by vagotomy to a mean of 3.8 f 2.1 mEq./l5 min., although the reduction in acid secretion varied from 18 to 100 per cent of the preoperative levels. In patients with recurrent ulceration, the secretion levels Vol. 115, April 1968
3.2 SD.
Acid after Antral Stimulation (mEq./l5 min.)
2.4
ranged from 1.5 to 13.7 mEq./l5 min., being generally higher in those in whom an early positive response to insulin was seen. In these patients the mean level of 7.6 f 3.2 mEq./l5 min. was similar to the value obtained in control patients not operated upon, whereas in patients with a late positive response to insulin the mean of 3.5 f 2.3 mEq./l5 min. was almost identical to the results found after complete vagotomy. It is clear that patients with an early positive response to insulin have acid secretions, both basal and histamine-stimulated, which are similar to those found in patients before operation, and that therefore recurrent ulceration is not surprising. The reason for recurrence in patients with a late positive response to insulin is more elusive, particularly when both basal and histamine-stimulated secretions in these patients are comparable to those found after complete vagotomy. Antral Stimulation. Meat extract stimulation differs from histamine infusion in that the stimulus is not continuous. We have used the peak fifteen minute output to describe the response, provided that this exceeds the basal level by at least 0.5 mEq. The duration of the meat extract response, and the relation of the peak response to the maximum histamine output provide other useful parameters. In the thirty-six patients with duodenal ulceration studied preoperatively, all responded to antral stimulation. (Table I.) The mean basal level of 1.0 f 0.9 mEq./l5 min. rose to a mean maximum output of 4.0 f 2.4 mEq./l5 min., with the response declining over the hour. Of the nineteen patients with a positive response to insulin, studies of this type were performed in sixteen. In these patients the mean basal level
Giles, Mason, and Clark
I
I\NTRAL 5TlMULATION
"ISTAMINE INFUSION
LA,E
RESPONSE
FIG. 1. Results of studies of antral stimulation and histamine-stimulated secretion (given in mEq./l5 min.) in patients with positive responses to insulin.
of 1.1 mEq./l5 min. rose to a mean maximum of 3.6 f 2.4 mEq./l5 min., and the response was maintained longer than it was in the control patients not operated on. The effect of operation in the thirty-six patients with duodenal ulcer was to abolish the response in all but thirteen patients, and in these the mean maximum postoperative response was 1.6 f 1.0 mEq./l5 min. Thus it appears that antral function tested in this way is generally abolished by complete vagotomy, but some function is retained, although at a reduced level, in about one third of the patients. In the majority of patients with recurrent ulcer, however, antral function is retained, and may even be enhanced, as suggested by the more prolonged secretion. It is important therefore to study in more detail the results in relation to early and late responses to insulin. Antral Function and Histamine Stimulation. Figure 1 illustrates the individual results of meat extract and histamine stimulation in sixteen patients with incomplete vagotomy divided into groups having early and late responses to insulin. In patients with an early positive response to insulin four show responses to antral stimulation similar to those obtained with histamine stimulation, indicating an active antral mechanism. In the patients with a late positive response, however, although antral function is retained, there is no evidence to suggest that it is particularly marked. Thus the reason for recurrent ulceration in these patients with late positive response remains obscure and cannot be explained either by excessive acid secretion or abnormal antral function. Recurrent Ulceration and Complete Vagotomy.
The results of secretion studies in the three patients with recurrent ulceration in whom the vagotomy appeared complete by the insulin test are shown in Figure 2. In the patient whose responses are represented in Figure 2A, not only is the basal secretion low, but also antral function is minimal and histamine secretion at a maximum of 1.8 mEq./l5 min. It would seem that factors other than those related to acid secretion are required to explain the recurrence in this case. In the remaining patients, however, antral function is quite marked, particularly in the patient whose responses are represented in Figure 2C, and it is striking how closely the response to antral stimulation resembles the maximal output of the stomach as determined by histamine infusion. It is tempting to imply that in these patients, despite complete vagotomy, the function of the antrum is retained sufficient to maintain secretion at an &erogenic level. Such an explanation is in accord with the proposals of Gillespie and Kay [Z] to explain recurrent ulceration after complete vagotomy. COMMENTS
Much of the controversy regarding operations for chronic duodenal ulceration centers around the incidence of recurrent ulceration, which is considered to be higher after vagotomy and gastric drainage compared with the incidence occurring after more radical operations such as partial gastrectomy. However, partial gastrectomy is often complicated by metabolic and nutritional complications found some years after operation, and it is pertinent therefore to enquire into the reasons for recurrent ulceration after vagotomy. In this study of twentytwo patients it is apparent that the common cause of recurrence is an inadequate operation, for in nineteen subjects there was evidence of incomplete vagotomy as judged by the insulin test. There is considerable difference of opinion both concerning the technic of performing the insulin test and in the interpretation of the results; this has recently been reviewed [7,8]. The criteria proposed by Hollander [P] have been considered too stringent by some authors, and perhaps the methods used in other secretory studies allow a better analysis. Ross and Kay [5] proposed the division of a positive response to insulin into early and late categories, according to whether or not the stimulation of American Journal of Surgery
Antral Function and Recurrent Ulceration secretion occurred in the first or second hour
ACID
after insulin was given. The results of the pres-
Mw
MEAT
EXTRACT
475 HISTAMINE
j-
ent study are in agreement with their findings, namely, that in patients with an early positive response the ability of the stomach to secrete acid under a maximal histamine stimulus was similar to that occurring in control patients not operated on. Thus, the secretory responses in fourteen of the patients with recurrent ulceration behave more or less like those in patients who have not had an operation. This observation is supported by the results of antral function tests, and indeed it is possible that a few of these patients may show excessive antral function. The significance of the late response to insulin is uncertain, for the secretory response to stimulation with histamine and meat extract is identical to that found after complete vagotomy. We had considered the possibility that these patients might demonstrate excessive antral function, but this was not shown. Ross and Kay [S] suggested that an early response implied that a large vagal nerve trunk had been left undivided, whereas with a late response the element of an undivided nerve was small. The risk of recurrence was considered to be greater in the former situation. It is of interest that in a follow-up study of patients with positive response to insulin tests [9] the incidence of recurrent ulceration in those with an early response was 36 per cent as compared with a 7 per cent incidence in those with a late response. The amount of acid secreted by the stomach after operation has often been held to be important in the liability to recurrent ulceration. This has generally been measured by maximal histamine stimulation. In patients with recurrent ulceration after partial gastrectomy, for example, acid secretion levels as high as those found in preoperative control patients have been described [I]. Scobie and Rovelstad [lo] suggested that after partial gastrectomy a residual secretory level of 15 mEq./hr. or more was likely to indicate a high risk of recurrence. The factors responsible for recurrence after gastrectomy may differ from those after vagotomy, but it is of some interest that all but one patient with an early positive response to insulin had secretion on histamine stimulation at a level of 15 mEq./hr. or more. Only one of the patients with a late response had such a high level of secretion, however, and in the remainder acid secretion was at a low level. HowVol. 115, April
1968
--
ACID Mw
B
ACID
4,
MEAT
EXTRACT
HISTAMINE
MEAT
EXIRACT
HISTAMINE
: 1
FIG. 2. Secretion studies in three patients (A, B, and C) with recurrent ulceration after complete vagotomy. In two of these patients antral stimulation approximates the output on maximal histamine stimulation.
ever, the results of pre- and postoperative studies in the patients with duodenal ulcer indicate that there are several with apparently successful surgery but in whom considerable amounts of acid can still be secreted. The question to be answered therefore is whether complete vagotomy can provide immunity from recurrent ulceration, regardless of the postoperative secretory acid levels. There were three patients with recurrent ulceration who had complete vagotomy, as judged by two tests giving negative results. In one of these patients the responses to secretory stimuli were so low that none of the hypotheses relating acid to recurrent ulcer can be adduced in explanation. In the other two patients, however, the response to histamine was within normal limits in one and was high in the other. In both patients antral stimulation produced acid levels similar to those obtained on maximal histamine stimulation. These patients appeared to have what has been described as a dominant antral mechanism [Z], and this may be the explanation of the recurrence. In these cases even complete vagotomy does not protect the subject from further ulceration, and antrectomy would be mandatory. As yet, however, no satisfactory method has been found to detect such patients before operation.
Giles, Mason, and Clark
476 SUMMARY
In twenty-two patients with recurrent ulceration after vagotomy and gastric drainage, nineteen were found to have incomplete vagotomy by the insulin test. Secretion studies using antral stimulation and maximal histamine infusion indicated that when the patient showed an early positive response to the insulin test, the gastric secretory responses were similar to those in control patients not operated upon. When patients had a late positive response to insulin, gastric secretory responses were similar to those in patients with complete vagotomy. Three patients had recurrent ulceration despite complete vagotomy. In two of these patients antral function was marked and this may provide an explanation for recurrence in these circumstances.
2.
3.
4. 5. 6.
7.
8.
9.
REFERENCES
10. 1. BRUCE, J., CARD, W. I., MARKS, I. W., and SIRCUS,
W. The rationale of selected surgery in the treat-
ment of duodenal ulcers. J. Roy. Coll. Surgeons Edinburgh, 4: 85, 1963. GILLESPIE, I. E. and KAY, A. W. The effect of medical and surgical vagotomy on the augmented histamine test in man. Brit. M. J., 1: 1557, 1961. LAWRIE, J. H., SMITH, G. M. R., and FORREST, A. P. M. The histamine infusion test. Lancet, 2: 270, 1964. HOLLANDER, F. Laboratory procedure in the study of vagotomy. Gastroenterology, 11: 419, 1948. Ross, B. and KAY, A. W. The insulin test after vagotomy. Gastroenterology, 46: 379, 1964. GILES, G. R. and CL-, C. G. Gastric secretion stimulated by meat extract in man. Scandinav. J. Gastroenterol., 1: 159, 1966. BACHRACH, W. H. Laboratory criteria for the completeness of vagotomy. Am. J. Digest. Dis., 7: 1071, 1962. BANKS, S., MARKS, I. N., and Louw, J. H. Histamine and insulin stimulated gastric secretion after selective and truncal vagotomy. Gut, 8: 36, 1967. BELL, P. R. F., CHECKETTS, R. G., JOHNSTON,D., and DUTHIE, H. L. The augmented histamine response after incomplete vagotomy. Luncet, 2: 978, 1965. Scosm, B. A. and ROVELSTAD, R. A. Anastomotic ulcer: significance of the augmented histamine test. Gastroenterology, 48: 318, 1965.
American Journal of Surgery
Function
and Recurrent
G. R. GILES, M.B., F.R.c.s., M. C. MASON,
Ulceration
B.SC.,B.M.,AND C. G. CLARK, M.D., CKM., F.R.C.S.,
Leeds, England
From the Department Leeds, England.
of
size 12 French
Surgery, University of Leeds,
gauge nasogastric tube, the resting contents of the stomach were discarded and basal secretions were obtained in fifteen minute collections over one hour using motor pump suction, interrupted at intervals with air insufflation to prevent blockage of the tube. Thereafter the following tests were performed : Histamine Stimulation. The procedure described by Lawrie, Smith, and Forrest [3] was used, with a continuous infusion of histamine acid phosphate at a dose of 0.04 mg./kg./hr. Secretions were collected in fifteen minute samples for one hour, and the secretory capacity of the stomach was calculated from the peak thirty minute output, and expressed as mEq. per fifteen minutes. Insulin Stimzclation. A procedure was used in which insulin was injected intravenously in a dose of 0.15 unit/kg. and secretions were collected for two hours. A positive response was recorded only when there was a rise both in acid concentration and output according to the criteria of Hollander [4], but we also noted whether the response was early (in the first hour) or late (in the second hour), as recommended by Ross and Kay [S]. Antral Stimulation. The technic described by Giles and Clark [6] was used in which a stable solution of meat extract, with pH adjusted to 7.0 by added bicarbonate, is introduced into the stomach and left for fifteen minutes before being completely aspirated. The secretions were collected over the next hour and the antral response was measured using the peak fifteen minute sample. All secretions were filtered through glass wool and a I ml. aliquot was used for titration with N/100 solid sodium hydroxide, using Topfer’s reagent as indicator. The results are expressed either as concentration in mEq./L. or as acid output in mEq. per
interest in the treatment of chronic duodenal ulceration by vagotomy and a gastric drainage procedure led us to examine the factors which might be concerned with recurrent ulceration. It is generally accepted that incomplete vagotomy is the major cause of recurrence, but it has been suggested [l] that in some cases even complete vagotomy will not always lower acid secretion sufficient to prevent further ulceration. In these patients it has been suggested [2] that the antrum may be capable of maintaining the acid output at a high level. We have therefore studied twenty-two patients with proved recurrent ulceration after vagotomy. The completeness of vagotomy was assessed by the insulin test, and the secretory capacity of the stomach was determined by histamine infusion. In addition we have used a simple test of antral function based on meat extract stimulation. The results of these studies have been compared with observations in thirty-six patients with duodenal ulceration examined before and after operation. ENEWED
R
MATERIAL AND METHODS
Of the twenty-two patients with recurrent ulceration after vagotomy and gastric drainage (nineteen had pyloroplasty and three gastroenterostomy) there were seventeen male and five female patients whose ages ranged from twenty-one to fifty-five years The control group consisted of thirty-six patients with chronic duodenal ulcer, thirty-one male and five female patients whose ages ranged from eighteen to sixty-eight years. These patients were treated by vagotomy and pyloroplasty, and in every case the vagotomy was judged complete by postoperative secretory studies. Gastric secretion studies were performed after a twelve hour overnight fast. After intubation with a
unit fifteen minutes. RESULTS
Insulin Stimulation Test. This test was performed on at least one occasion in each patient. In three patients with proved recurrent ulceration, a negative response was recorded, but 472
American Journal of Surgery
Antral Function and Recurrent Ulceration
473
TABLE I RESULTSOF HISTAMINEAND ANTRAL STIMULATIONTESTS
Patients With duodenal ulcer (preoperative test) With duodenal ulcer (postoperative test, insulin negative) With recurrent ulcer and early positive response to insulin With recurrent ulcer and late positive response to insulin
Basal Acid Secretion (mEq./l5 min.)
Acid after Histamine Stimulation (mEq./lS min.)
36
1.2 f
1.0 S.D.
9.2 f
36
0.3 f
0.3 SD.
3.8 + 2.1 S.D.
14
1.5 zt 0.9 SD.
7.6 f
3.2 SD.
0.2
3.6 f
2.3 S.D. i
No. of Patients
4.0 III 2.4
3.6 f 5
only after tests on two separate occasions. In the remaining nineteen patients with recurrent ulceration, there was a positive response which occurred in the first hour (early) in fourteen, and in the second hour (late) in five. This division of positive responses into early and late has been maintained in considering the results of other secretion studies. Basal Secretion. The effect of vagotomy on spontaneous basal secretion is shown in Table I. In thirty-six patients with duodenal ulcer the preoperative level was 1.2 f 1.0 mEq./l5 min. and after complete vagotomy this was reduced to 0.3 f 0.3 mEq./l5 min. with thirteen subjects rendered achlorhydric. In the nineteen subjects with recurrent ulceration and a positive insulin test, only one had achlorhydria, a patient who showed a late positive response to insulin. In the remainder the level of basal acid secretion appeared to be related to the type of response to insulin. When there was an early positive response, the basal secretion was 1.5 f 0.9 mEq./l5 min., which resembled the level in patients prior to operation. With a late positive response the basal acid was 0.2 mEq./l5 min., a value similar to that found in patients with complete vagotomy. Histamine-Stimulated Secretion. Table I shows the results of the histamine tests in thirty-six patients before and after complete vagotomy. The maximum acid output before operation ranged from 3.4 to 21.0 mEq./l5 min., with a mean of 9.2 f 3.2 mEq./l5 min. This was reduced by vagotomy to a mean of 3.8 f 2.1 mEq./l5 min., although the reduction in acid secretion varied from 18 to 100 per cent of the preoperative levels. In patients with recurrent ulceration, the secretion levels Vol. 115, April 1968
3.2 SD.
Acid after Antral Stimulation (mEq./l5 min.)
2.4
ranged from 1.5 to 13.7 mEq./l5 min., being generally higher in those in whom an early positive response to insulin was seen. In these patients the mean level of 7.6 f 3.2 mEq./l5 min. was similar to the value obtained in control patients not operated upon, whereas in patients with a late positive response to insulin the mean of 3.5 f 2.3 mEq./l5 min. was almost identical to the results found after complete vagotomy. It is clear that patients with an early positive response to insulin have acid secretions, both basal and histamine-stimulated, which are similar to those found in patients before operation, and that therefore recurrent ulceration is not surprising. The reason for recurrence in patients with a late positive response to insulin is more elusive, particularly when both basal and histamine-stimulated secretions in these patients are comparable to those found after complete vagotomy. Antral Stimulation. Meat extract stimulation differs from histamine infusion in that the stimulus is not continuous. We have used the peak fifteen minute output to describe the response, provided that this exceeds the basal level by at least 0.5 mEq. The duration of the meat extract response, and the relation of the peak response to the maximum histamine output provide other useful parameters. In the thirty-six patients with duodenal ulceration studied preoperatively, all responded to antral stimulation. (Table I.) The mean basal level of 1.0 f 0.9 mEq./l5 min. rose to a mean maximum output of 4.0 f 2.4 mEq./l5 min., with the response declining over the hour. Of the nineteen patients with a positive response to insulin, studies of this type were performed in sixteen. In these patients the mean basal level
Giles, Mason, and Clark
I
I\NTRAL 5TlMULATION
"ISTAMINE INFUSION
LA,E
RESPONSE
FIG. 1. Results of studies of antral stimulation and histamine-stimulated secretion (given in mEq./l5 min.) in patients with positive responses to insulin.
of 1.1 mEq./l5 min. rose to a mean maximum of 3.6 f 2.4 mEq./l5 min., and the response was maintained longer than it was in the control patients not operated on. The effect of operation in the thirty-six patients with duodenal ulcer was to abolish the response in all but thirteen patients, and in these the mean maximum postoperative response was 1.6 f 1.0 mEq./l5 min. Thus it appears that antral function tested in this way is generally abolished by complete vagotomy, but some function is retained, although at a reduced level, in about one third of the patients. In the majority of patients with recurrent ulcer, however, antral function is retained, and may even be enhanced, as suggested by the more prolonged secretion. It is important therefore to study in more detail the results in relation to early and late responses to insulin. Antral Function and Histamine Stimulation. Figure 1 illustrates the individual results of meat extract and histamine stimulation in sixteen patients with incomplete vagotomy divided into groups having early and late responses to insulin. In patients with an early positive response to insulin four show responses to antral stimulation similar to those obtained with histamine stimulation, indicating an active antral mechanism. In the patients with a late positive response, however, although antral function is retained, there is no evidence to suggest that it is particularly marked. Thus the reason for recurrent ulceration in these patients with late positive response remains obscure and cannot be explained either by excessive acid secretion or abnormal antral function. Recurrent Ulceration and Complete Vagotomy.
The results of secretion studies in the three patients with recurrent ulceration in whom the vagotomy appeared complete by the insulin test are shown in Figure 2. In the patient whose responses are represented in Figure 2A, not only is the basal secretion low, but also antral function is minimal and histamine secretion at a maximum of 1.8 mEq./l5 min. It would seem that factors other than those related to acid secretion are required to explain the recurrence in this case. In the remaining patients, however, antral function is quite marked, particularly in the patient whose responses are represented in Figure 2C, and it is striking how closely the response to antral stimulation resembles the maximal output of the stomach as determined by histamine infusion. It is tempting to imply that in these patients, despite complete vagotomy, the function of the antrum is retained sufficient to maintain secretion at an &erogenic level. Such an explanation is in accord with the proposals of Gillespie and Kay [Z] to explain recurrent ulceration after complete vagotomy. COMMENTS
Much of the controversy regarding operations for chronic duodenal ulceration centers around the incidence of recurrent ulceration, which is considered to be higher after vagotomy and gastric drainage compared with the incidence occurring after more radical operations such as partial gastrectomy. However, partial gastrectomy is often complicated by metabolic and nutritional complications found some years after operation, and it is pertinent therefore to enquire into the reasons for recurrent ulceration after vagotomy. In this study of twentytwo patients it is apparent that the common cause of recurrence is an inadequate operation, for in nineteen subjects there was evidence of incomplete vagotomy as judged by the insulin test. There is considerable difference of opinion both concerning the technic of performing the insulin test and in the interpretation of the results; this has recently been reviewed [7,8]. The criteria proposed by Hollander [P] have been considered too stringent by some authors, and perhaps the methods used in other secretory studies allow a better analysis. Ross and Kay [5] proposed the division of a positive response to insulin into early and late categories, according to whether or not the stimulation of American Journal of Surgery
Antral Function and Recurrent Ulceration secretion occurred in the first or second hour
ACID
after insulin was given. The results of the pres-
Mw
MEAT
EXTRACT
475 HISTAMINE
j-
ent study are in agreement with their findings, namely, that in patients with an early positive response the ability of the stomach to secrete acid under a maximal histamine stimulus was similar to that occurring in control patients not operated on. Thus, the secretory responses in fourteen of the patients with recurrent ulceration behave more or less like those in patients who have not had an operation. This observation is supported by the results of antral function tests, and indeed it is possible that a few of these patients may show excessive antral function. The significance of the late response to insulin is uncertain, for the secretory response to stimulation with histamine and meat extract is identical to that found after complete vagotomy. We had considered the possibility that these patients might demonstrate excessive antral function, but this was not shown. Ross and Kay [S] suggested that an early response implied that a large vagal nerve trunk had been left undivided, whereas with a late response the element of an undivided nerve was small. The risk of recurrence was considered to be greater in the former situation. It is of interest that in a follow-up study of patients with positive response to insulin tests [9] the incidence of recurrent ulceration in those with an early response was 36 per cent as compared with a 7 per cent incidence in those with a late response. The amount of acid secreted by the stomach after operation has often been held to be important in the liability to recurrent ulceration. This has generally been measured by maximal histamine stimulation. In patients with recurrent ulceration after partial gastrectomy, for example, acid secretion levels as high as those found in preoperative control patients have been described [I]. Scobie and Rovelstad [lo] suggested that after partial gastrectomy a residual secretory level of 15 mEq./hr. or more was likely to indicate a high risk of recurrence. The factors responsible for recurrence after gastrectomy may differ from those after vagotomy, but it is of some interest that all but one patient with an early positive response to insulin had secretion on histamine stimulation at a level of 15 mEq./hr. or more. Only one of the patients with a late response had such a high level of secretion, however, and in the remainder acid secretion was at a low level. HowVol. 115, April
1968
--
ACID Mw
B
ACID
4,
MEAT
EXTRACT
HISTAMINE
MEAT
EXIRACT
HISTAMINE
: 1
FIG. 2. Secretion studies in three patients (A, B, and C) with recurrent ulceration after complete vagotomy. In two of these patients antral stimulation approximates the output on maximal histamine stimulation.
ever, the results of pre- and postoperative studies in the patients with duodenal ulcer indicate that there are several with apparently successful surgery but in whom considerable amounts of acid can still be secreted. The question to be answered therefore is whether complete vagotomy can provide immunity from recurrent ulceration, regardless of the postoperative secretory acid levels. There were three patients with recurrent ulceration who had complete vagotomy, as judged by two tests giving negative results. In one of these patients the responses to secretory stimuli were so low that none of the hypotheses relating acid to recurrent ulcer can be adduced in explanation. In the other two patients, however, the response to histamine was within normal limits in one and was high in the other. In both patients antral stimulation produced acid levels similar to those obtained on maximal histamine stimulation. These patients appeared to have what has been described as a dominant antral mechanism [Z], and this may be the explanation of the recurrence. In these cases even complete vagotomy does not protect the subject from further ulceration, and antrectomy would be mandatory. As yet, however, no satisfactory method has been found to detect such patients before operation.
Giles, Mason, and Clark
476 SUMMARY
In twenty-two patients with recurrent ulceration after vagotomy and gastric drainage, nineteen were found to have incomplete vagotomy by the insulin test. Secretion studies using antral stimulation and maximal histamine infusion indicated that when the patient showed an early positive response to the insulin test, the gastric secretory responses were similar to those in control patients not operated upon. When patients had a late positive response to insulin, gastric secretory responses were similar to those in patients with complete vagotomy. Three patients had recurrent ulceration despite complete vagotomy. In two of these patients antral function was marked and this may provide an explanation for recurrence in these circumstances.
2.
3.
4. 5. 6.
7.
8.
9.
REFERENCES
10. 1. BRUCE, J., CARD, W. I., MARKS, I. W., and SIRCUS,
W. The rationale of selected surgery in the treat-
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