GASTRIC EMPTYING OF SOLID FOOD IN NORMAL MAN AND AFTER SUBTOTAL GASTRECTOMY AND TRUNCAL VAGOTOMY WITH PYLOROPLASTY

Transcription

1 GASTROENTEROWGY 72: , 1977 Copyright 1977 by The Williams & Wilkins Co. Vol. 72, No.2 Printed in U.8A. GASTRIC EMPTYING OF SOLID FOOD IN NORMAL MAN AND AFTER SUBTOTAL GASTRECTOMY AND TRUNCAL VAGOTOMY WITH PYLOROPLASTY I. L. MAcGREGOR, M.B., CH.B., F.R.A.C.P., P. MARTIN, M.S., AND J. H. MEYER, M.D. Departments of Medicine and Nuclear Medicine, Veterans Administration Hospital, and University of California, San Francisco, California Alterations in gastric emptying are considered contributory to many sequelae of peptic ulcer surgery. The application of a validated method of firmly tagging solid food has enabled the measurement of the rates and patterns of gastric emptying in normal subjects, subtotal gastrectomy, and vagotomy and pyloroplasty (V&P). Normal persons emptied with a linear pattern at a mean rate of 27.96% per hr. Subtotal gastrectomy patients showed up to three phases in their emptying pattern, which, over all, approximated an exponential pattern, with a mean rate constant of min- 1 and calculated t1/2 of 23.3 min. V&P subjects divided into two groups: (1) slow emptying with a linear pattern and mean rate of 17.64% per hr; (2) rapid emptying with exponential pattern and mean rate constant of min-i, t1/2 of 17.7 min. The slow gastric emptying rate and slow passage of chyme through the small intestine in one-half of the V &P group presumably allows greater efficiency of digestion and absorption and may account for the over-all less severe nutritional disturbances after V &P. Previous studies have shown that liquid test meals are emptied very rapidly from the stomach of patients with subtotal gastrectomy (STG) or with truncal vagotomy and pyloroplasty (V &P).l Such rapid gastric emptying markedly altered the ratio between the rate at which the meal entered the gut and the rate at which biliary or pancreatic secretion entered the bowel during the period when most of the liquid meal left the stomach. 1 Digestive disturbances may result. 2-4 Because liquid test meals are not typical of table food, we questioned whether solid food also emptied abnormally rapidly from the stomachs of these ulcer-operated patients. Until the last decade it was impossible to quantitate movement of solid material from the stomach. In patients with STG, radioopaque beads or other material mixed with solids had been shown semiquantitatively to empty from the stomach rapidly.5 Combining external y-radiation counting with isotopic labeling of food has been the method used more recently for quantitating rates of emptying of solids Results have been conflicting (see below), partly because isotopic markers adsorbed to the surface of solid food readily dissociated. 12 Accordingly, we have studied gastric emptying with a new method that utilizes the incorporation of a y emitting isotope into the matrix of solid food so that Received March 26, Accepted July 14, Address requests for reprints to: Ian L. MacGregor, M.D. (lllh), Veterans Administration Hospital, 4150 Clement Street, San Francisco, California This study was supported in part by Grant 1 ROl AM180l4-0l from the National Institutes of Health. The authors are grateful to Ms. Judith Haupt for expert secretarial assistance. marker does not dissociate appreciably from the solid phase. 12 Most persons studied also had had previous studies of the gastric emptying of liquid test meals, allowing comparisons between emptying of liquids and of solids. Methods For each study 1 to 2 mc op9mtc-labeled sulfur colloid were injected into a wing vein of a conscious chicken. After 30 min the chicken was killed and the liver was removed, diced into pieces of about 1 cm 3, and cooked in a microwave oven to a rubbery consistency. It was then mixed with a 7 1 /2-ounce can of commercial beef stew and fed to the subject, who ate the meal along with 200 ml of water in about 3 to 5 min. Postprandial times (below) refer to midprandial time as zero time. The subject then faced a scintillation camera, standing, while counts and images were collected for a period (3 to 15 min) over the stomach and intestinal area; the subject was then allowed to stand or sit away from the camera for a short time (5 to 15 min). Counting and imaging was frequently repeated over several hours, or until it was apparent that less than 20% of the chicken liver remained in the stomach, as determined by estimates made during the study. The scintillatior:. camera was equipped with two electronically determined areas of interest (AOI's) within the field of view, adjustable in size, shape, and position. One AOI was set to include only the stomach. The other AOI constituted the entire field of view. Using a diverging collimator, this field of view extended from the stomach to the pelvis. The counts for each AOI were accumulated in 20-sec frames. The ratio of counts in the stomach AOI, S, divided by the counts in the total AOI, T, was considered the initial estimate of the fraction of chicken liver remaining in the stomach. An immediate, discontinuous histogram was made of SIT versus time, from which the times for data collection and resting were determined. 206

2 February 1977 GASTRIC EMPTYING OF SOLID FOOD 207 All data were recorded on videotape; when irregularities were noted, or when the electronic AOI over the stomach appeared to be misplaced, the tape was played back, with a new placement of the stomach AOI, providing the data for subsequent analysis. Scintiphotographs were also collected during the course of the study to support the numerical data, to validate the placement of the AOI, and to display the movement of the 99mTc in the intestines as well (fig. 1). Lateral transmission-emission scintiphotographs were also made to give a qualitative indication ofthe orientation and the relative depth of the stomach from the anterior abdominal surface. Studies were performed on 22 subjects as follows: normal (5); V&P (9); STG with gastroduodenostomy (STG-BI) (3); and STG with gastrojejunostomy (STG-BIl) (5). All studies were done in the afternoon, after the subject had eaten a light breakfast. The research protocol was approved by the Committee on Human Research, University of California, San Francisco (228705). All subjects gave informed consent. Analysis Poststudy analysis included decay corrections and an additional empirical correction to account for two sources of systematic error: use of a diverging collimator meant that the sensitivity of the camera varied with the lateral and axial position of the activity. As the activity passed from stomach into the more centrally located intestines, an increase in the observed total count rate occurred. It was also noted that the depth and orientation Qfthe stomach varied, causing a marked axial displacement of stomach with respect to intestines in several of the operated subjects. Thus, the decay-corrected total count rate over the course of a study increased. A correction for this was made by constraining the corrected total counts (Tc) to be constant. The constraint was imposed by multiplying the stomach counts (S) by a fraction (Fs) to yield a corrected stomach counts estimate, Sc. The fraction was adjusted so that Tc = T - S + Sc was constant with time over the study, as determined by the slope of the linear regression line of Tc versus time. Results The major interpretations were made from the graphs of the amount of label remaining in the stomach versus elapsed time for each subject. The time course of emptying had several characteristics that occurred repeatedly, providing several indices by which to classify the observations. These indices included: (1) the projected time to empty entirely; (2) the number of phases observed; (3) the rate of emptying within each phase; (4) the goodness offit within each phase to a linear model of emptying; and (5) the goodness of fit over-all to a linear or an exponential model of emptying. Time for Complete Emptying When grouped by the projected time to empty entirely, the subjects were clearly divided three ways: a short time to empty of between 20 min and 21/2 hr, a FIG. 1. Representative scintophotographs of radioactivity in gastrointestinal tract. A, normal subject 135 min with highlighting of area of interest over stomach; B, C, and D, sequential views of subtotal gastrectomy with gastroduodenostomy (STG-Bl) subject at 4, 30, and 60 min, respectively, showing passage of meal from stomach into small intestine. B shows discrete points of radioactivity in upper small intestine which represent solid pieces of chicken liver. Such large discrete radioactivity-emitting sources were not seen in normal subjects, presumably owing to the presence of a normally functioning antral-pyloric mechanism.

3 208 MACGREGOR ET AL. Vol. 72, No.2 medial time of between 3 and 4 hr, and a long time of from 4 to 7 hr. All 5 normal subjects and only these 5 subjects had total emptying times of3 to 4 hr. A portion of the vagotomy subjects (5 of 9) had projected total emptying times of greater than 4 hr. The other vagotomy subjects and all of the STG subjects had short total emptying times, 20 min to 21/2 hr. The confidence in grouping in this manner is considered good. In those subjects in which the greatest extrapolation to completion of emptying was necessary, the over-all behavior was of a single, linear phase. Thus, such extrapolation was as valid for these subjects as for any others. Phases of Gastric Emptying A variety of emptying patterns was observed, with several notable features. The occurrence of a single phase was predominant in most cases. Normal f;ubjects. All normal subjects emptied in a linear pattern, especially after the first 20 to 30 min (fig. 2). During this initial time, a delay 'in getting started was seen in 3 of the 5 normal subjects. Vagotomy and pyloroplasty. All V &P subjects with slow gastric emptying displayed a single linear phase. The initial behavior (0 to 30 min) was not distinctly different from the main phase (fig. 2). The V&P subjects with rapid emptying (4 of 9) emptied rapidly for 20 to 30 min, and then slowed to a rate similar to, then slower than that of normal subjects for the remainder (fig. 2) of the study. A rather abrupt transition separated these phases for each person, but is not clearly demonstrated after averaging for a group of subjects (fig. 2). The pattern for the pool of all V &P subjects showed an initial tendency to empty faster than normal subjects, then slowed to become slower than normal subjects, but at no time were differences from normal subjects significant (data not shown). Subtotal gastrectomy. All STG-BI subjects clearly needed at least two phases to explain their emptying patterns. As a group these subjects (3) displayed an initial precipitous emptying (15 to 65%) followed by a delay of 20 to 30 min, and then followed by a smooth, nonlinear curve, steep at first, becoming less steep with time, reaching 5 to 15% remaining at about 2 hr. Emptying patterns among the STG-BII subjects were less consistent. One subject needed almost 3 hr to empty and displayed three apparent phases. Two subjects appeared to empty rapidly, with one phase. Another emptied over one-half of the meal within 5 min, needing about 2 hr for the remainder, whereas another emptied entirely in 20 min. Because of overlapping patterns and small numbers of STG-BI, the STG groups have been combined (fig. 3). Rates of Gastric Emptying The over-all rates of emptying are shown in table l. Whenever a phase appeared to be linear the slope ofthe line of best fit was determined for the data within that phase. For all normal subjects the slopes were in the range of 21 to 36% per hr. The linear correlation of percentage of meal remaining in stomach with time (15- min intervals for all subjects for 3 hr or until empty) gave an over-all rate constant of 28.0% emptied per hr (r = 0.94). For the V&P subjects emptying slowly the range was 10 to 18% per hr, with a mean rate constant of 17.6% per hr (r = 0.86). For the V&P subjects emptying rapidly, the initial phase emptying rates ranged from 130 to 165% per hr, with a mean of 146 ± 13% per hr, whereas the second phase rates ranged from 23 to 50% per hr, with a mean of 34 ± 12% per hr. Among the STG-BI subjects, a linear model fit the data for times greater than 40 min. In this phase the range of emptying rates was 18 to 40% per hr, with a mean of 27 ± 8% J::. u 70 a E 0 en 60 c: 50 0 Q) ::E 40 ~ o t. (. ) meal Time minutes FIG. 2. Percentage of radioactivity in stomach versus time for normal, (e), slow emptying truncal vagotomy and pyloroplasty (V & P) (0), and fast emptying V&P (6) subjects. Points represent mean values ± SEM. Significance of difference from normal group: *p < 0.05; # P < 0.01 (unpaired t-test) t meal Time (minutes) FIG. 3. Percentage of radioactivity in stomach versus time for normal subjects (e) and combined subtotal gastrectomy (STG) groups (A). Points represent mean values ± SEM. P versus normal: *< 0.025; 6 < 0.01; 0 < 0.005; # < (unpaired t-test).

4 February 1977 GASTRIC EMPTYING OF SOUD FOOD 209 TABLE 1. Rate constants and t1/2 values for gastric emptying Group (no.) Emptying rate r P tl/2 (B)" min Normal (5) 0.466%/min 0.94 < % emptied (linear) in min Slow V&P (5) 0.294%/min 0.86 < % emptied (linear) in 170 min P vsnormal <0.05 Fast V&P (4) min < (exponential) STG (8) min < (exponential) a The emptying rate was derived by determining the coefficient (B) for y = A - Bt, linear model, or y = Ae- Bt, exponential model, where y = amount remaining in stomach, as % [(AOI SI AOI T) x 100]; B = emptying rate, in percentage per minute (linear) or minutes- 1 (exponential); t = elapsed time in I5-min intervals from midprandial time; A = initial amount (-100%); r = correlation coefficient for model used. t1/2 for exponential emptying = (log.10)1 -B. per hr. However, the precipitous emptying of an initial fraction gave rapid over-all emptying rates. For the 2 STG-BII subjects with a single phase pattern, the rates were 50 and 52% per hr, whereas another STG-BII subject, emptying precipitously at first, emptied at a rate of 24% per hr thereafter, and had completely emptied in 1.6 hr. The 1 subject who displayed three phases had rates of7% per hr initially, followed by 105% per hr, then 5% per hr for times greater than 1 hr. The over-all rate constants for the linear (normal and slow V &P) groups could not be statistically compared with the more closely exponential or multiphasic patterns seen in the fast V &P and STG groups. The mean percentage emptied at regular time intervals was therefore calculated and statistical differences (unpaired t-test) between groups are shown in figures 2 and 3. The mean amount of meal emptied in the STG and fast V &P groups exceeded the corresponding value in normal subjects throughout the entire study period (figs. 2 and 3). A statistical difference between the slow V &P and normal subjects was seen during the last 30 min of the 3-hr study period (fig. 2). Discussion Data published to date on the use of radioactive scanning techniques for the study of the gastric emptying rate of solid food have been based on the assumption that the isotope used emptied in a manner representative of the meal itself. However, the use of nonfood markers 5 and soluble markers which dissociate from the solid food in the stomach 6, 8, 10, 11 make such data questionable. The method we have used for labeling solid food has been validated to the extent that the intracellularly incorporated 99mTc-Iabeled sulfur colloid is firmly bound to its solid food carrier and is resistant to solubilization by peptic digestion. 12 All operated subjects were studied at least 1 year after their surgical procedure. Surgical results were good to excellent. There was little over-all change from preoperative weight. One postvagotomy subject had moderate intermittent diarrhea dating from the time of his surgery. As in our previous studies,l the upright position was chosen for the study as it represents the usual postcibal position. To avoid repeated exposure to radiation, studies were not repeated in any subject. We have therefore no information on the reproducibility of this method. This was studied by Heading et ai., 13 who used filter paper soaked in 99mTc-Iabeled sulfur colloid and coated with plastic to mark the emptying rate of his cornflakes meal. Two studies on successive days showed day to day variation, but less variation was noted between replicate studies in 1 patient than was noted among several patients. Normal subjects. The method so used demonstrated a linear pattern of emptying versus time in all 5 subjects within a narrow range (21 to 36% per hr, mean 28% per hr). In the companion study1 the same group of5 normal subjects emptied a meal of fat, protein, and hypertonic glucose linearly but at a faster rate (36.9% per hr). Statistical comparison of the slopes by analysis of variance 14 showed that the solid meal was emptied significantly (P < 0.01) more slowly than the liquid meal. Likewise, other studies 12, 13 have similarly documented faster emptying of liquids than solids in normal subjects. Subtotal gastrectomy. The pattern and rate of emptying of solids after STG has not been extensively investigated. Dozois et al. 15 studied the effect of distal antrectomy on the emptying of M saline and radioopaque plastic spheres from the stomach of the dog and found that the operation slightly increased the saline emptying rate and greatly accelerated the emptying rate of the plastic spheres. They concluded that the terminal antrum and pylorus are of minor importance in the regulation of liquid emptying, but of great importance in the gastric emptying of solids. Bucklei' and Heading et al. 13 have demonstrated rapid emptying of mashed potato and cornflakes meals, respectively, after STG, but their choice of nonfood markers precludes unequivocal acceptance of their results. We found the emptying rate and patterns of solid food in the STG patients to be more variable than that seen with the liquid meal. 1 One patient with STG-BII had an over-all rate of solid emptying only a little faster than in normal subjects, whereas the others emptied excessively rapidly. Nevertheless, in most subjects there was a fast initial phase of emptying that would be expected to produce an altered ratio of meal emptying rate to pancreatic or biliary secretion rate into the proximal bowel, just as with liquid meals. 1 Truncal vagotomy and pyloroplasty. Several investigators have studied emptying of solid meals in patients with V&P's, but results have been inconsistent (table 2). Such inconsistencies may have arisen from variations in (1) the posture of the subjects during the studies; (2) the time after surgery at which the patients were

5 210 MACGREGOR ET AL. Vol. 72, No. 2 Reference Method Subjects Time after no. studied surgery 5 Radioopaque spheres 26 V&P's Not specified mixed with mashed potatoes 6 51Cr203 adsorbed to 16 V&P's >9 wk postop eggs + porridge + vs. preop milk TABLE 2. Studies of gastric emptying of solid food in V &P subjects 7 129CS adsorbed to zir- V&P's; wk; 91-4 conium PO. + eggs, controls mo; yr toast, and milk 8 C,l Cr203 adsorbed to 10 V&P's; days milk, bread, + controls porridge 9 mcs adsorbed to V&P's; days; 4-6 zirconium PO. resin + controls mo eggs, toast, + milk 10 51Cr 2 0" adsorbed to 5 V&P's; 10 <3 mo milk + porridge + controls bread 11 "Cr203 adsorbed to 10 vagotomy, 5-<2 wk eggs + cornflakes + unspecified 5-> 3 mo milk drainage; 5 controls Empty- ing rate Position of subjects Emptying pattern in V&P's studied; (3) methods for measurement of emptying of solids; and (4) the proportion of subjects within small populations being studied that belong in one or another unidentified subgroup. Some studies have demonstrated that emptying of solids is more rapid in the upright than in the supine position lo and that emptying of solid food becomes less delayed with time after surgery.7 The present results indicate that V &P's, as a group, empty solid food at an initially faster and then slightly slower rate than do normal subjects. However, because there appeared to be two distinct subgroups in the population sampled, it probably is not valid to categorize V &P's as a single group. Others have also noted unpredictable effects of truncal vagotomy on gastric emptying of solids, slowly emptying in some and accelerating it in others (table 2). These results contrast with those in patients with STG's (above), in which all subjects studied emptied solids rapidly. The slowed emptying patterns of solid meals in some of the V &P patients contrasted to the abnormally rapid emptying of liquid meals in the very same patients. I These findings underscore the more moderate disparity between rates of gastric emptying of liquids versus solids in normal subjects,12, 13 as well. The present findings also explain previous discrepancies between separate studies in patients after V&P, illustrating slow or normal rates of emptying of solid meals on the one hand, and other studies showing a rapid emptying of liquid test meals. I 6-18 Although these results are generally consistent with previous findings in patients with V &P's, showing nor- Not specified Delayed vs. normal Delayed Sitting at 90 d Biphasic with exponential Rapid late phase; 40% emptied in 1st 10 min postop vs. 12.5% preop Supine Linear-exponential; variable Normal slowing, 1-16 wk; normal at 1-3 yr Supine Linear, delayed in 6/10 Delayed Supine Exponential; grossly delayed Normal days postop; slightly delayed delayed at 4-6 mo Supine or erect Exponential; posture did not Normal- (standing) affect emptying in normal delayed subjects but lying slowed emptying in V&P's; standingnormal lying-delayed Supine Exponential; Normalnormal in 3/5 } in both va- delayed delayed in 2/5 gotomy groups Mean tl/2 increased mal or moderately delayed emptying of solids, 5, 7-11 such comparisons may be specious. The Na51Cr203 marker adsorbed to solid food in some of those studies 6, 8, 10, II is known to distribute itself between liquid and solid phases; 12 because there may be a wide dissociation between the accelerated emptying of liquids and the slowed emptying of solids in patients with V &P's, the net behavior of a marker like Na51Cr203 is unpredictable, depending critically on factors regulating the movement of liquid, such as supine versus erect posture. 16 Whether similar considerations apply to the 129Cs-resin method is unknown. Finally, the present study suggests that there are subgroups of patients that cannot be defined on clinical grounds (because the mild postoperative symptoms admitted to by some of our patients did not correlate with demonstrated emptying patterns or with the emptying rates of liquid test meals). If such subgroups truly exist, this and previous studies using small groups of patients may give rise to results that depend on the chance preponderance of one subgroup or another in the sampled population. Because of this problem of sampling, it is not clear how common the two subgroups observed are among all patients with V &P's. Nevertheless, the present finding of a subgroup of 5 of 9 subjects who emptied solids abnormally slowly after V &P is consistent with the older clinical observations l9 that about 40% of all subjects with truncal vagotomy develop gastric stasis unless a "drainage" procedure is performed, assuming that those with asymptomatic delayed gastric emptying after V &P would have been the ones with symptomatic gastric stasis after truncal va-

6 February 1977 GASTRIC EMPTYING OF SOLID FOOD 211 gotomy without a pyloroplasty. The gastric emptying rate of solid food after V &P has been claimed to be dependent on the type of drainage procedure used: those with a Heineke-Mikulicz pyloroplasty emptied slowly and those with a Finney pyloroplasty emptied rapidly. 20 Six of the present patients, including 4 of the slow emptiers, had had a Heineke-Mikulicz pyloroplasty; 2 patients with that procedure emptied rapidly. Two fast emptiers had had a Jaboulay pyloroplasty. The type of drainage procedure in the 9th patient was not determined. There was no significant association between the type of drainage procedure and emptying rate in the sample studied. Delayed emptying of solid food in some of the V &P's, as opposed to rapid emptying of solids in all STG's, may serve to explain differences in postoperative nutrition. Although patients with V &P tend to be lighter in weight than a matched normal control population,2l their postoperative weight, on the average, remains slightly higher than in patients with STG-BII's.22 Studies with liquid test meals have not explained this nutritional distinction, as abnormalities in rates of gastric emptying of liquids! or in postcibal luminal concentrations of pancreatic enzymes and/or bile salts! have been at least as severe in V &P's as in STG's. In the present studies the solid food moved more slowly through the gastrointestinal tract in those patients with V &P who exhibited slow gastric emptying. Presumably, the slower intestinal transit of food in the V &P patients was the outcome of slower gastric emptying, as a similar correlation between gastric emptying time and intestinal transit time has been noted previously by others.!h Slower passage of food through the gastrointestinal tract of one-half of the V &P's might account for more complete digestion and absorption. REFERENCES 1. MacGregor IL, Parent J, Meyer JH: Gastric emptying of liquid meals and pancreatic and biliary secretion after subtotal gastrectomy or truncal vagotomy and pyloroplasty in man. Gastroenterology 72: , Lundh G: Intestinal digestion and absorption after gastrectomy. Acta Chir Scand Suppl 231:1-83, MacKay C: Postgastrectomy steatorrhea. Am J Surg 120: , Fields M, Duthie HL: Effect of vagotomy on intraluminal digestion of fat in man. Gut 6: , Buckler KG: Effects of gastric surgery upon gastric emptying in cases of peptic ulceration. Gut 8: , Colmer MR, Owen GM, Shields R: Pattern of gastric emptying after vagotomy and pyloroplasty. Br Med J 2: , Cow ley DJ, Vernon p, Jones T, et al: Gastric emptying of solid meals after truncal vagotomy and pyloroplasty in human subjects. Gut 13: , Hancock BD, Bowen-Jones E, Dixon R, et al: The effect of metoclopramide on gastric emptying of solid meals. Gut 15: , George WD, Royston CR, Cowley DJ, et al: Gastric emptying of a solid meal after long and short pyloroplasties (abstr). Br J Surg 60:307, Hancock BD, Bowen-Jones E, Dixon R, et al: The effect of posture on the gastric emptying of solid meals in normal subjects and patients after vagotomy. Br J Surg 61: , Harvey RF, Mackie DB, Brown NJG, et al: Measurement of gastric emptying time with a gamma camera. Lancet 1:16-18, Meyer JH, MacGregor IL, Gueller R, et al: 99 Tc-tagged chicken liver as a marker of solid food in the human stomach. Am J Dig Dis 21: , Heading RC, Tothill P, McLoughlin GP, et al: Gastric emptying rate measurement in man: a double isotope scanning technique for simultaneous study of liquid and solid components of a meal. Gastroenterology 71:45-50, Snedecor GW, Cochran WG: Statistical Methods. Sixth edition. Ames, Iowa, Iowa State University Press, Dozois RR, Kelly KA, Code CF: Effect of distal antrectomy on gastric emptying of liquids and solids. Gastroenterology 61: , McKelvey STD: Gastric incontinence and post-vagotomy diarrhea. Br J Surg 57: , Aylett E, Wastell C: Gastric secretion and emptying before and after vagotomy and pyloroplasty with and without pentavlon pentagastrin. Am J Dig Dis 14: , Hall WH, Read RC: Effect of vagotomy on gastric emptying. Am J Dig Dis 15: , Grimson KS, Taylor HM, Trent JC, et al: The effect of transthoracic vagotomy upon the function of the stomach and upon the early clinical course of patients with peptic ulcer. South Med J 39: , Davies WT, Griffith GH, Owen GM, et al: The effect of vagotomy and drainage operations on the rate of gastric emptying in duodenal ulcer patients. Br J Surg 61: , Wastell C: Long-term clinical and metabolic effects of vagotomy with either gastrojejunostomy or pyloroplasty. Ann R Coil Surg Engl 45: , Cox AG: The outcome of truncal vagotomy and a drainage procedure, chap 5. In Vagotomy on Trial. Edited by AG Cox, JA Williams. London, Heinemann Medical Books, 1973, p 67-83