PROGRESS IN GASTROENTEROLOGY

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1 GASTROENTEROLOGY 68: , 1975 Copyright 1975 by The Williams & Wilkins Co. Vol.68, No.6 Printed in U.SA. PROGRESS IN GASTROENTEROLOGY VAGOTOMY IN THE ELECTIVE TREATMENT OF DUODENAL ULCER THEODORE R. ScHROCK, M.D. Department of Surgery, University of California, San Francisco, California The reintroduction of truncal vagotomy by Dragstedt and Owens 1 in 1943 inaugurated the "physiological" era of surgery for duodenal ulcer. Previous surgical approaches to ulcer had been adopted empirically from experience with gastric cancer. Vagotomy, in contrast, was a rational clinical test of a hypothesis about the pathogenesis of duodenal ulcer derived from laboratory experiments. The original version, transthoracic truncal vagotomy without drainage, quickly proved to be unsatisfactory, but with one modification or another, vagotomy has earned a secure position in the surgical treatment of this disease. A new technique, proximal gastric vagotomy, now vies for consideration. As information about the new vagotomy accrues, it must be compared with the record of the older vagotomies. This review is limited to various forms of vagotomy, with or without gastric resection, in the elective treatment of duodenal ulcer. Much of the vast literature on the subject lacks scientific merit. Valid comparisons of operations are available only from controlled trials, a relatively recent innovation. Results of individual operations over longer periods were judged from reports of large series of patients, thoroughly described, comprehensively followed, analyzed in detail, and tabulated by interval after operation. Received December 4, Accepted January 16, Address requests for reprints to: Dr. Theodore R. Schrock, Department of Surgery, University of California, San Francisco, California The author is indebted to Lawrence W. Way, M.D., for critical review of the manuscript Surgical Anatomy of the Abdominal Vagal Nerves The anterior (left) and the posterior (right) vagal trunks enter the abdomen through the esophageal hiatus (fig. 1). There are two trunks in 70 to 90% of individuals and three or more large nerves in the remainder. 2 3 Small fibers from the esophageal plexus or the trunks themselves are found on the abdominal esophagus in an additional 50% of patients. 2 Truncal vagotomy consists of dividing all vagal structures on or about the lower esophagus (fig. 1); if only two trunks are severed, vagotomy is incomplete in about 75% of cases. The hepatic division of the anterior trunk gives off small branches of unknown function to the pylorus and duodenum on its way to the liver. The gastric division travels down the lesser curvature as the anterior nerve of Latarjet 4 ; it supplies the body and fundus before it terminates in the antrum, where it resembles a "crow's foot." 5 The celiac division of the posterior trunk goes to the celiac ganglia; the gastric division, the posterior nerve of Latarjet, pursues a course similar to its anterior counterpart. Bilateral selective vagotomy denervates the stomach completely but spares the hepatic and celiac divisions. Proximal gastric vagotomy preserves these divisions and also the nerves of Latarjet, severing only the branches to the body and fundus (fig. 1). Rationale of Vagotomy: Effects on Acid Secretion Dragstedt and Owens 1 postulated that hypersecretion of acid by patients with

2 1616 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 Anterior (left) vagal trunk -----:l a. Truncal vagotomy, B. Selective vagotomy r-:z~~""'-- C. Proximal gastric vagotomy Posterior nerve of Latarjet ---, ---H---7/--ff-----tH Branches to body & fundus Anterior nerve of Latarjet t+l~ Pyloric branch "crow's foot" FIG. 1. Schematic representation of the abdominal vagal nerves and the levels of transection in various forms of vagotomy. (Redrawn after Goligher' and other sources.) duodenal ulcer was due to excessive vagal tone. The concept of vagal hypertonia has not been substantiated, in part because vagal tone cannot be measured, 6 but the reduction in acid secretion obtained by dividing the vagal nerves has been confirmed amply. Truncal vagotomy lowers basal acid secretion by 70 to 80% and reduces the peak acid response to histamine or pentagastrin by 50 to 70%. 7 8 In the cephalic phase of secretion, parietal cells are stimulated directly by the vagi and also by gastrin released from the antrum; both mechanisms are abolished by truncal vagotomy. 7 Release of gastrin in the gastric phase is not prevented; fasting and postprandial serum gastrin levels are normal or increased after truncal vagotomy. 7 9 Changes in basal and stimulated acid secretion after selective gastric or proximal gastric vagotomy are similar to those following truncal vagotomy Antrectomy alone reduces peak acid response to histamine by 50%, 14 and antrectomy-vagotomy lowers both basal and histamine-stimulated acid secretion by 90%. 15 Fasting and postprandial serum gastrin concentrations are lower after vagotomyantrectomy if gastrojejunostomy (BII) is performed instead of gastroduodenostomy (BI). 9 Food-induced release of gastrin from the duodenum in the latter situation is believed responsible for these differences. 9 Truncal Vagotomy Latarjet 4 reported the first vagotomy for benign ulcer in He added pylorectomy to avoid gastric stasis, and in the same decade others performed vagotomy with various ancillary procedures. The work of these pioneers was largely ignored, however, until Dragstedt and Owens 1 brought attention to the operation by in-

3 June 1975 PROGRESS IN GASTROENTEROLOGY 1617 traducing transthoracic truncal vagotomy without drainage. Gastric retention was recognized as a complication of this procedure by 1945, 16 and the transabdominal approach with gastrojejunostomy or pyloroplasty became standard. More than a quarter-century of experience with truncal vagotomy is available for review. Gastrojejunostomy and several types of pyloroplasty are considered together in the first part of this discussion, and the relative merits of various drainage procedures are considered separately. Operative Mortality Cox et al. 17 reported 0.9% operative mortality in 8215 elective cases collected from the literature between 1963 and Operative Complications Complications of the vagotomy itself occurred in 4% of more than 1000 cases. 18 These surgical accidents included splenic rupture (3.0%), esophageal perforation (0.5%), postoperative hemorrhage necessitating reoperation (0.3%), and other (0.2%). Leakage from the gastrojejunostomy or pyloroplasty suture line occurred in about 2% of the patients in one series. 19 Recurrent Ulceration Recurrence is defined as follows: 20 (1) persistence of ulceration following the operation; (2) recurrence after an interval of apparent absence; (3) peptic ulceration in a new site; or (4) suspected ulceration unless it is proved later that ulceration does not exist. Many authors do not subscribe to this definition or do not define recurrence at all. Recurrences are further categorized as "proved" or "suspected" based on whether or not symptoms are substantiated by radiographic, endoscopic, or surgical evidence of ulcer. 21 Recurrence rate is calculated as follows: 1. Recurrences are cumulative; once a recurrence, always so, even though additional therapy cures the ulcer. 2. The denominator is the number of living, traced patients at or beyond a specified interval after operation. Patients who die from any cause (with or without ulcer) and patients lost to follow-up are excluded. 3. Results are expressed as 5-year (or other) recurrence rate. Table 1 lists recurrence rates after elective truncal vagotomy and drainage for duodenal ulcer. In each of the reports cited, more than 100 living patients were traced for at least 5 years after operation. The wide disparity of results at 10 years undoubtedly reflects many differences in these studies. The interval from operation to recurrence in patients followed well beyond 10 years was recorded by three authors Of 110 recurrent ulcers, 50% were diagnosed within 5 years, 31% between 5 and 10 years, and 19% more than 10 years after operation. The need for lengthy follow-up to detect the true rate of recurrence was known from the experience with gastrojejunostomy and is no less applicable to truncal vagotomy-drainage. Side Effects The incidence of unpleasant sequelae after any operation for ulcer is partly determined by definition of terms, diligence of inquiry, objectivity of the inquirer, and length of follow-up. The mechanisms underlying many of these symptoms have not been defined; a detailed discussion is beyond the scope of this review. Diarrhea. Cox and Bond 30 recorded an increase in the frequency of bowel movements in 71%, transient diarrhea in 10%, and episodic diarrhea in 23% -of patients after truncal vagotomy-drainage. Altered bowel habit was pleasing to many, annoying to others (about 5%), and disabling to a few (1% or less). Diarrhea has been linked so closely to vagal nerve section that the adjective "post-vagotomy" is sometimes applied. This symptom was a distressing and frequent complication of transthoracic vagotomy without drainage, and often it was treated successfully by gastrojejunostomy. 31 Diarrhea after truncal vagotomy-drainage probably stems from a combination of factors, including vagal denervation of extragastric viscera, total denervation of the stomach, and the drainage procedure. 32

4 1618 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 TABLE 1. Five- and 10-year recu"ence rates after truncal vagotomy and drainage Author No. of Completeness patients of follow-up' Patients with recurrence' Proved Suspected Total 5-yr recurrence % % Evans et a! d 39 (7.6) Dellipiani et a! (15.0) Goligher eta! (8.5) Goligher eta! (14.0) Postlethwait d 21 (9.3) Total (9.6) 10-yr recurrence Feggetter and Pringle (6.7) Nobles d 24 (23.5) Stempien eta! d 44 (27.3) Wastell _d - d 7 (5.1) Total (14.9) a Patients followed for minimum period stated (excludes deaths and untraced cases). 'Percentage of total patients undergoing operation. 'Recurrence rates calculated as described in the text. "Not stated. Males and females in the trial, randomized or not randomized. Dumping syndrome. Careful questioning elicited mild symptoms of dumping in up to 50% and severe dumping in 1 to 4% 17 following truncal vagotomy-drainage. This syndrome is attributed to unregulated gastric emptying. 33 Late dumping (hypoglycemia) occurred in 10% of cases. 17 Vomiting. Vomiting of food, bile, or both troubled 10 to 20% of patients and was severe in 1 to 2% Other gastric symptoms. About onethird of patients complained of early satiety, nausea, or flatulence of varying severity. 17 Dysphagia. Truncal vagotomy caused transient dysphagia in 18% 17 and severe dysphagia in 3.6%. 35 Responsible mechanisms include esophageal edema, hematoma, fibrosis, reflux esophagitis, and perhaps denervation ofthe lower esophagus. 35 Steatorrhea. Increased fecal fat content was found in one-half of patients. 36 Hypocalcemia was detected in 4% of a group investigated more than 15 years following operation. 37 Gallstones. Dilation of the denervated gallbladder was correlated with gallstone formation. 38 Controlled studies are needed to prove the relationship. Weight loss. Methods of expressing weight reduction vary. Twenty-four per cent of men and 32% of women were more than 6 kg below standard weight after 15 years. 37 Postprandial symptoms limited food intake in many of these patients. Anemia. Wheldon et al. 37 found that 44% of men and 84% of women were anemic (hemoglobin below normal limits) more than 15 years following truncal vagotomydrainage. Anemia was of the iron deficiency type. Over-all Patient Satisfaction Visick 39 determined four grades of patient satisfaction after gastric surgery, which correspond to excellent, good, fair, and poor results. Visick's system or the equivalent was used in five studies to evaluate patients more than 5 years after truncal vagotomy-drainage In these 925 collected cases, results were excellent in 50%, good in 23% (total 73% good or excellent), fair in 14%, and poor in 13%. The percentage of poor results was consistent in the five series (9% to 16%).

5 June 1975 PROGRESS IN GASTROENTEROLOGY 1619 Method of Drainage Only three controlled comparisons of drainage with truncal vagotomy have been published. Pyloroplasty and gastrojejunostomy were studied in a prospective, randomized trial by Kennedy et al. 34 Pyloroplasty (Heinecke-Mikulicz) was performed in 204 patients, and gastrojejunostomy (retrocolic) was used in 200 patients. After 2 years, the only statistically significant difference was in bilious vomiting, which was more frequent with gastrojejunostomy (16% versus 6%) and more often severe with gastrojejunostomy ( 4.4% versus 0.6%). Recurrence rates were similar (pyloroplasty 4.8%, gastrojejunostomy 3.0%), and Visick grading was virtually identical prior to reoperations for recurrence or bilious vomiting. Two kinds of pyloroplasty with truncal vagotomy were studied in a prospective, randomized trial by Hayden and Read. 41 The Heinecke-Mikulicz variety was associated with delayed gastric emptying more commonly than the Finney procedure, but operative complications, diarrhea, dumping, weight loss, and other sequelae were similar in a short ( <1 year) follow-up. Payne et al. 42 found no differences in acid secretion, fat absorption, or fat excretion in another controlled study of truncal vagotomy with gastrojejunostomy or the same two types of pyloroplasty. Objective evidence does not favor one method of drainage over another when truncal vagotomy is performed electively for duodenal ulcer. Statistical comparisons of groups of patients, however, do not exclude the possibility that one specific drainage procedure is best suited for each individual patient, an hypothesis which cannot be tested. Kennedy et al. 34 performed gastrojejunostomy without randomization in some cases because of the findings at operation. The practical implication is that a surgeon may select a drainage procedure depending on the shape of the patient's stomach, the presence of pyloroduodenal inflammation or scarring, or merely out of personal preference without incurring the risk of statistically poorer over-all results compared to some other technique. Recurrent Ulcer and Incomplete V agotomy Early in the experience with truncal vagotomy, Dragstedt et al. 31 asserted that poor results were due to incomplete nerve section and that ulcer could persist or recur if even small vagal fibers were overlooked. How frequently incomplete vagotomy is responsible for recurrence has been debated ever since. The central issue is whether truncal vagotomy-drainage is faulty in design, for at least some patients with duodenal ulcer, or is a perfect design all too often ineptly applied. Completeness of vagotomy is assessed most commonly by postoperative measurement of acid secretion during insulininduced hypoglycemia. Hollander 43 established arbitrary criteria for categorizing results as "positive" (incomplete vagotomy) or "negative" (complete vagotomy). Ross and Kay 44 further divided the positives into early and late, and many other alternative criteria for interpretation have been proposed. Dignan 45 found that 3.8% to 38.6% of vagotomized subjects had positive responses to insulin, depending on the criteria of positivity. At least 50% of patients will have a positive insulin test by Hollander's criteria 43 if examined repeatedly following truncal vagotomy-drainage. The number of responders increases with the interval after operation (table 2); twice as many positives were detected in the delayed as in the immediate tests in both studies. Watkin and Duthie 48 reported that 28 of 75 patients converted from negative to positive, and 3 patients went from positive to negative over the long term. Smith et al. 49 serially tested insulin-negative subjects; 40% gave a positive response eventually, and the conversion from negative to positive occurred within 6 months of operation. Regeneration of nerves, growth by sprouting, or recovery from neuropraxia have been postulated, but these phenomena are difficult to document in man. The ability of insulin tests to identify patients with incomplete vagotomy is fairly well substantiated, although the relationship cannot be proved because there is no independent criterion of completeness

6 1620 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 TABLE 2. Response to insulin in relation to interval after truncal vagotomy and drainage Test Gillespie eta!." (74 patients) Kronborg" (320 patients) Immediate 2 weeks % Early positive. % Late positive'.... % Total positive Interval after operation... %Negative days Delayed Interval after operation.... % Early positive.... % Late positive' % Total positive... %Negative a Criteria of Hollander." Positive in the first 60 min post-insulin. 'Positive in the 2nd hr post-insulin. 1-4 years years" of vagotomy. 5 Fawcett et al. 51 explored the esophageal hiatus in 59 insulin-positive patients (Hollander's criteria 43 ) with recurrent ulceration after truncal vagotomydrainage; they found an intact trunk or trunks in 85% and slender vagal strands in 15%. Johnston et al. 52 were unable to correlate the timing of positive response (early or late) with the size of residual vagal fibers; a stout trunk was identified in most cases. Although insulin tests probably detect all or most incomplete vagotomies, as few as 60% of patients with recurrent ulcer have a positive response Insulin tests, therefore, are imperfect means of predicting recurrence. In various reports, 10% (8% to 55%) of insulin responders and 2% (0% to 5%) of nonresponders by Hollander's criteria 43 develop recurrent ulcer after truncal vagotomydrainage Ulcer recurs in 25% (13% to 68%) if the response is early and in 5% (3.6% to 24%) if it is late The trend, however, is to dispense with arbitrary classification of response to insulin as "positive" or "negative" in favor of reporting changes in acid secretion as numerical values Two studies which analyzed results quantitatively found that postoperative insulin tests have limited power to discriminate recurrence from nonrecurrence Insulin tests detect incomplete, but adequate, vagotomy as well as incomplete and inadequate vagotomy and cannot distinguish between the two classes. The question of faulty design of truncal vagotomy-drainage applies especially to ulcer patients who are marked hypersecretors. Kronborg 57 is just one of many authors who correlated preoperative acid secretion with results of vagotomy to determine if the method of surgical management could be tailored to the individual patient. He suggested that patients with preoperative peak acid outputs of more than 46.4 meq per hr after histamine were unsuitable for treatment with vagotomy alone because of a high incidence of recurrence. A corollary of this concept is that marked hypersecretors have less margin for error (incomplete vagotomy carries a greater risk of recurrence). This attractive hypothesis has stimulated conflicting opinions, and the issue is not resolved. Gastrin-secreting tumors and inadequate drainage procedures cause some of the recurrences after truncal vagotomydrainage, and perhaps some patients cannot be vagotomized for anatomic or technical reasons; revagotomy converted insulin tests from positive to negative in only one-half of patients ' 58 Nevertheless, the evidence that recurrence is usually due to preventably incomplete vagotomy, while not conclusive, is too strong for the surgeon to escape responsibility for most of these failures. Johnston and Goligher 59 found that com-

7 June 1975 PROGRESS IN GASTROENTEROLOGY 1621 pleteness of vagotomy as revealed by insulin tests varied from 0% to 50% among a group of surgeons, irrespective of their status as consultants or registrars. Several intraoperative methods to ensure complete denervation have been proposed, 60 but in actuality most surgeons shun them because they are cumbersome, time-consuming, or restrictive of anesthetic flexibility. 61 The technique of vagotomy is "neither self-evident nor simple, " 62 but gadgetry should not be expected to compensate for lack of thoroughness of dissection. Methods for improving adequacy of vagotomy were discussed by Alexander Williams. 62 Selective Vagotomy Selective gastric vagotomy was designed to preserve the extragastric vagal fibers in the hope of minimizing unpleasant side effects; later, the possibility of obtaining more complete gastric denervation by this technique was suggested. Jackson 63 and Moore 64 described total anterior and selective posterior vagotomy, and Franksson 65 selectively divided the gastric vagal supply bilaterally. Selective vagotomy was abandoned because of gastric stasis, but it was revived, with a drainage procedure, by Griffith and Harkins in the late 1950's. 66 It is now performed as bilateral selective vagotomy with drainage by most of its proponents. The level of vagal section is indicated in figure 1. Operative mortality. Operative mortality in three large series of elective cases was 0.. 3% Operative complications. Morbidity is similar to that of truncal vagotomy Recurrent ulceration. Ulcer recurred in a mean of 6.3% (3.9, 6.0, and 9.2%) of 378 patients followed for 4 years or longer after bilateral selective vagotomy with drainage The insulin test was positive by Hollander's criteria in 21% 68 or 70% 70 of patients after 5 years. Kronborg et al. 70 detected conversion from negative to positive between immediate and delayed testing, but Amdrup and Jensen 68 found no change; immediate tests were performed 10 days after operation in the study of Kronborg et al. 70 and 2 to 4 months postoperative in the report of Amdrup and Jensen. 68 About half the patients with recurrent ulcer were insulin-positive (Hollander). 68 Side effects. Looseness of stools appeared in 15 to 20% but severe diarrhea was rare to nonexistent. Dumping occurred in 16 to 56% and was severe in 7% or less Development of gallstones, hopefully avoided by preservation of the hepatic division, was not evaluated in the three long term studies Over-all patient satisfaction. Good or excellent results were obtained in 84%, fair in 6%, and poor in 10% of patients followed for 5 years or longer Method of drainage. Kennedy et al. 71 studied pyloroplasty and gastrojejunostomy with selective vagotomy in a prospective, randomized trial. After 2 to 5 years, there were several minor but no significant differences between the two groups. The authors expressed a preference for gastrojejunostomy, mainly because it is reversible should the need arise. Controlled trials of selective and truncal vagotomy. Two prospective, randomized trials compared selective and truncal vagotomy with drainage after a minimum follow-up of 5 years (table 3). Recurrence rates were equal in one 70 and lower after selective in the other. 36 In the series of Kronborg et al. 70 insulin tests were positive at 5 years by Hollander's criteria in 45% of truncal and 69% of selective vagotomy patients. Kennedy et al. 36 did not perform delayed tests, but an earlier report 72 showed fewer positive responses to insulin in the selective vagotomy group ( 4% versus 21 %) 10 days after operation. Dumping was more frequent following selective vagotomy in one study, 36 but the difference was not statistically significant. Diarrhea was less common after selective denervation in both studies; severe diarrhea occurred in none of the selective patients and in 2.9% 70 or 4.3% 36 of the truncal vagotomies. Other small differences in postoperative symptoms were recorded, with a slight tendency to favor selective vagotomy. Clinical status at 5 years by Visick grading was good to excellent in 96% of the selective and 87% of the truncal group. 36

8 1622 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 TABLE 3. Prospective, randomized trials of selective and truncal vagotomy with drainage No. of Recurrence, Author patients proved and suspected Dumping Diarrhea Kronborg eta!. 70 Truncal 38 Selective 43 Kennedy et a!. 36 Truncal 50 Selective 50 Kronborg et al. 70 used a different system, but again results were slightly better after selective vagotomy. Another clinical trial did not randomize cases fully. 73 These controlled studies fulfilled the expectation that diarrhea would be less a problem with selective vagotomy, but whether gastric denervation is more often complete with this technique remains an open question. Objective evidence that selective vagotomy offers marginally superior results appeared after the introduction of proximal gastric vagotomy, and the attention of many inclined toward selective denervation was diverted to the newer procedure. V ago to my with Antrectomy Preliminary clinical results of truncal vagotomy-antrectomy were reported by several groups in the early 1950's This operation has attracted strong support because the addition of antrectomy provides more profound lowering of acid output than vagotomy alone, as discussed earlier in this article, and probably protects against recurrence in the patient whose vagotomy is incomplete. "Antrectomy" here refers to a distal gastric resection of 50% or less. Continuity is restored by gastroduodenostomy (BI) or gastrojejunostomy (BII). Operative mortality. The operative mortality of elective truncal vagotomy-antrectomy for duodenal ulcer was 1.2% (0% to 3.4%) in 2264 collected cases "80 Herrington et al. 81 reported 1.5% mortality in 3584 patients, but 31 of the 55 deaths were in emergency cases. Operative complications. Leakage from the duodenal stump is a complication of % % % gastric resection with a BII anastomosis. It occurred in 2% of patients. 78 ' 80 Recurrent ulceration. The 5-year recurrence rate was 1.8% in Postlethwait's series 25 and 5.1% in the report of Goligher et al. 21 ; four of the six recurrences in the latter study were "very dubious." Ulcer recurred in 0. 7% 79 and 0.6% 81 of patients in two large series totaling 4036 cases which were not tabulated by length of follow-up. Side effects and over-all patient satisfaction. Results of truncal vagotomy-antrectomy appear similar to those of vagotomydrainage, but the outcome of controlled trials must be considered in order to make valid comparisons. BI versus BII. There are many claims that either BI or BII is a superior method of reconstruction after vagotomy-antrectomy, but no objective evaluation has been made. Vagotomy in Prospective, Randomized Clinical Trials The first prospective, randomized clinical trial of operations for duodenal ulcer was conducted in Glasgow and reported by Forrest in Studies of pyloroplasty and gastrojejunostomy or selective and truncal vagotomy-drainage36 70 were discussed earlier in this review. Table 4 lists other trials which evaluated vagotomy in some form (excluding proximal gastric vagotomy). Detailed discussion of these studies cannot be given here, but a few conclusions are pertinent: 1 Over-all results of various operations for duodenal ulcer were marginally different and slightly favored truncal vagotomyantrectomy. 2 Operative mortality was about the same for vagotomy-drainage (0.57%) and

9 June 1975 PROGRESS IN GASTROENTEROLOGY 1623 TABLE 4. Prospective, randomized trials of operations for duodenal ulcer Authors Operations compared No. of patients Truncal vagotomy-drainage vs. truncal vagotomy-antrectomy vs. subtotal gastrectomy Goligher eta!. 21 Truncal-gastrojejunostomy 126 Truncal-antrectomy (BII) 132 Subtotal (BII) 117 Postlethwait" Truncal-drainage (P or GJ) 337 Truncal-antrectomy (Bl or II) 674" Subtotal (Bl or II) 346 Howard et a!. ' Truncal-pyloroplasty 100 Truncal-antrectomy (BII) 73 Truncal vagotomy-drainage vs. truncal vagotomy-antrectomy Subtotal (BII) 94 Jordan and Condon 19 Truncal-drainage (P or GJ) 108 Truncal-antrectomy (Bl or II) 92 Irani eta!. Truncal-pyloroplasty 64 Truncal-antrectomy (BII) 62 Selective vagotomy-drainage vs. selective vagotomy-antrectomy Sawyers and Scott I Selective-pyloroplasty 63 Selective-antrectomy (Bl or II) 57 Truncal vagotomy-drainage vs. subtotal gastrectomy Cox Truncal-gastrojejunostomy 81 a Includes antrectomy and hemigastrectomy. Subtotal (BII) 79 gastric resection with or without vagotomy (0.81%). These values are means for all the studies in table 4. 3 The 2-year recurrence rate was 9.6% for truncal vagotomy-drainage and 2.1% for truncal vagotomy-antrectomy (means from the table). 4 Diarrhea was more common after any operation involving truncal vagotomy, and severe diarrhea was limited almost exclusively to truncal vagotomy. 5. Weight loss was slightly more frequent after the gastric resections (antrectomy or subtotal). Other nutritional and metabolic problems were little different. 6. From 5% to 15% of patients were dissatisfied after any of these operations. These trials must be interpreted in context. All operations were elective. Each study contained an "escape clause" which permitted a surgeon to exclude patients from randomization because of age, general condition, or operative findings, and the low mortality rates probably reflected this exercise of surgical judgement as much as any factor. Follow-up periods were brieffor some of these studies, and the full impact of recurrence and nutritional sequelae was not felt. Although viewed in the aggregate the trials suggested that all operations were equal, important differences in such features as recurrence rates appeared in individual trials. Results of the prospective trials afford the surgeon the opportunity to achieve both major objectives of ulcer surgery: survival of the patient and cure of the ulcer diathesis. More than incidentally, it should be noted that the standard of excellence for operative mortality in elective surgery for duodenal ulcer is now 1% or less! One may intend to perform the operation with the lowest recurrence rate (vagotomy-antrectomy), but opt instead for vagotomy-drainage if the patient's condition is poor or if the duodenum is badly inflamed. Controlled trials have quieted the voices of those who insist that one operation has fewer long term side effects than another; all are about the same, and approximately 10% of patients are dissatisfied. Hence, the search for the ideal operation goes on.

10 1624 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 Proximal Gastric Vagotomy Proximal gastric vagotomy (parietal cell vagotomy, highly selective vagotomy, and many other synonyms) evolved from laboratory studies by Griffith and Harkins. 87 Holle and Hart 88 reported the first clinical application, with a drainage procedure, in Proximal gastric vagotomy without drainage was performed in patients with duodenal ulcer by Johnston and Wilkinson 89 and Amdrup and Jensen 90 and reported in This operation has the anticipated advantage of eliminating side effects such as dumping because gastric emptying is normal. It has been used mainly for elective operations, although Johnston et al. 91 recommend it for bleeding, obstruction or perforation also. Goligher 5 described and illustrated one technique for performing proximal gastric vagotomy (fig. 1). Precise definition of the antrum-corpus junction (by ph testing of the gastric mucosa) to determine the distal limit of gastric denervation was practiced by Amdrup and Jensen 90 but is probably unnecessary. 5 The longest follow-up is about 5 years; results, therefore, are preliminary. Operative mortality. Johnston et al. 92 had no mortality in 350 patients. Scattered reports of deaths have appeared. Operative complications. Necrosis of the lesser curvature of the stomach after proximal gastric vagotomy has been reported. 93 Recurrent ulceration. Two suspected and no proved recurrences developed in the Leeds series of 58 patients followed for more than 2 years, a recurrence rate of 3.4% 94 ; several other reports of low recurrence rates over the short term were published also. High incidence of recurrence was reported by Moberg and Hedenstedt 95 (10.4% or 12.5% in 48 patients after 3 years) Madsen and Kronborg 96 (13.3% or 14.8% in 27 or 30 patients after 1 year), W astell et al. 97 ( 18.8% in 16 patients at 3 to 12 months), and Liedberg and Oscarson 98 (20% in 20 patients after 1 year). Reductions in acid secretion after proximal gastric vagotomy were similar to those after truncal or selective vagotomy Johnston et al. 11 found a significant increase in basal acid secretion between tests conducted 2 to 3 months and 12 to 24 months after operation. Postoperative response to insulin by Hollander's criteria was negative in 97% at 1 week and negative in only 43% to 53% at 1 year. 12 Exaggerated release of gastrin by the innervated antrum was not found after proximal gastric vagotomy Kragelund et al. 102 reported reduced, but still significant, acid output in response to meat extract in postoperative patients. Side effects. Johnston et al. 82 found significantly less diarrhea, and Humphrey et al. 33 detected less dumping after proximal gastric vagotomy without drainage compared to truncal or selective vagotomy with drainage in patients evaluated "blind" with respect to the type of vagotomy. Wilkinson and Johnston 103 recorded nearly normal gastric emptying and small bowel transit following proximal gastric vagotomy. Gastric stasis apparently causing gastric ulcer was reported by other groups. Over-all patient satisfaction. Goligher 94 reported 90% good to excellent, 5% fair, and 5% poor results in 58 patients after 2 years of follow-up. Comment. It is apparent that not all surgeons who have attempted proximal gastric vagotomy have mastered the technique. If denervation of the parietal cell mass is frequently incomplete and if tests of gastric secretion are not made to identify these technical failures, the familiar argument of faulty design versus inexpert application will be waged unendingly in this arena as it has with truncal vagotomy. It would be well for surgeons in general to exercise restraint in the adoption of proximal gastric vagotomy until the results of controlled trials and longer follow-up of the British and Scandinavian experiences are available. The theoretical potential for recurrence will be debated until data settle the issue. It is this reviewer's opinion that recurrence rates are likely to approximate those of truncal vagotomy-drainage unless: (1) denervation of the parietal cell mass is more often complete; (2) basal and stimulated acid secretion are lowered further; or (3) gastric stasis is avoided more surely. Pre-

11 June 1975 PROGRESS IN GASTROENTEROLOGY 1625 liminary evidence gives little cause for optimism on at least the first two scores, because acid secretion after proximal gastric vagotomy is similar to that observed after truncal vagotomy. Many may share the attitude of Kennedy et al 34 that the success rate of established operations has taken us to the point of diminishing returns in the quest for a perfect operation. Perhaps 90% success in the most refractory patients with duodenal ulcer is the best that can be achieved. It is too early to judge if proximal gastric vagotomy will improve on that figure. Goligher 94 suggested that proximal gastric vagotomy may prove to be the ideal minimal operation for duodenal ulcer: relatively free of side effects, effective in most, but amenable to supplementation with any other operation for those patients in need. Only experience will determine just how minimal proximal gastric vagotomy is and how many patients will be in need. REFERENCES 1. Dragstedt LR, Owens FM Jr: Supra-diaphragmatic section of the vagus nerves in treatment of duodenal ulcer. Proc Soc Exp Bioi Med 53: , Ruckley CV, Falconer CWA, Small WP, eta!: Selective vagotomy: a review of the anatomy and technique in 100 patients. Br J Surg 57: , Skandalakis JE, Rowe JS Jr, Gray SW, et a!: Identification of vagal structures at the esophageal hiatus. Surgery 75: , Latarjet MA: Resection des nerfs de l'estomac. Technique operatoire. Resultats cliniques. Bull Acad Nat Med 87: , Goligher JC: A technique for highly selective (parietal cell or proximal gastric) vagotomy for duodenal ulcer. Br J Surg 61: , Fordtran JS: Acid secretion in peptic ulcer, chap 14. In Gastrointestinal Disease. Pathophysiology, Diagnosis, Management. Edited by MH Sleisenger, JS Fordtran. Philadelphia, WB Saunders, 1973, p Walsh JH: Control of gastric secretion, chap 12. In Gastrointestinal Disease. Pathophysiology, Diagnosis, Management. Edited by MH Sleisenger, JS Fordtran. Philadelphia, WB Saunders, 1973, p Jepson K, Lari J, Humphrey CS, et a!: A comparison of the effects of truncal, selective and highly selective vagotomy on maximal acid output in response to pentagastrin. Ann Surg 178: , Stern DH, Walsh JH: Gastrin release in postoperative ulcer patients: evidence for release of duodenal gastrin. Gastroenterology 64: , Clarke RJ, Allan RN, Alexander Williams J: The effect of retaining antral innervation on the reductions of gastric acid and pepsin secretion after vagotomy. Gut 13: , Johnston D, Wilkinson AR, Humphrey CS, eta!: Serial studies of gastric secretion in patients after highly selective (parietal cell) vagotomy without a drainage procedure for duodenal ulcer. I. Effect of highly selective vagotomy on basal and pentagastrin-stimulated maximal acid output. Gastroenterology 64:1-11, Johnston D. Wilkinson AR, Humphrey CS, eta!: Serial studies of gastric secretion in patients after highly selective (parietal cell) vagotomy without a drainage procedure for duodenal ulcer. II. The insulin test after highly selective vagotomy. Gastroenterology 64:12-21, Jordan PH Jr: Parietal cell vagotomy without drainage. Early evaluation of results in the treatment of duodenal ulcer. Arch Surg 108: , Broome A, Olbe L: Studies on the mechanism of the antrectomy-induced suppression of the maximal acid response to histamine in duodenal ulcer patients. Scand J Gastroenterol4: , McGuigan JE, Trudeau WL: Serum gastrin levels before and after vagotomy and pyloroplasty or vagotomy and antrectomy. N Eng! J Med 286: , Dragstedt LR, Schafer PW: Removal of the vagus innervation of the stomach in gastroduodenal ulcer. Surgery 17: , Cox AG, Spencer J, Tinker J: Clinical results reviewed, chap 9. In After Vagotomy. Edited by J Alexander Williams, AG Cox. New York, Appleton-Century-Crofts, 1969, p Wirthlin LS, Malt RA: Accidents of vagotomy. Surg Gynecol Obstet 135: , Jordan PH Jr, Condon RE: A prospective evaluation of vagotomy-pyloroplasty and vagotomyantrectomy for treatment of duodenal ulcer. Ann Surg 172: , Weinberg JA: Pyloroplasty and vagotomy for duodenal ulcer. In Current Problems in Surgery. Chicago, Year Book Medical Publishers, Inc. April, Goligher JC, Pulvertaft CN, de Dombal FT, et a!: Five-to eight-year results of Leeds/York controlled trial of elective surgery for duodenal ulcer. Br Med J 2: , Evans RH, Zajtchuk R, Menguy R: Role of

12 1626 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 vagotomy and gastric drainage in the surgical treatment of duodenal ulcer. Results of a tenyear experience at the University of Chicago Hospitals. Surg Clin North Am 47: , Dellipiani A W, Macleod IB, Thomson JWW, et a!: Gastroenterostomy and vagotomy for chronic duodenal ulcer. Gut 10: , Goligher JC, Pulvertaft CN, Irvin TT, et a!: Five-to eight-year results of truncal vagotomy and pyloroplasty for duodenal ulcer. Br Med J 1:7-13, Postlethwait RW: Five year follow-up results of operations for duodenal ulcer. Surg Gynecol Obstet 137: , Feggetter GY, Pringle R: The long-term results of bilateral vagotomy and gastrojejunostomy for chronic duodenal ulcer. Surg Gynecol Obstet 116: , Nobles ER Jr: Vagotomy and gastroenterostomy. A 15-year follow up of 175 patients. Am Surgeon 32: , Stempien SJ, Dagradi AE, Lee ER, et al: Status of duodenal ulcer patients ten years or more after vagotomy-pyloroplasty (V-P). Am J Gastroenterol 56:99-108, Wastell C: Long-term clinical and metabolic effects of vagotomy with either gastrojejunostomy or pyloroplasty. Ann Roy Coli Surg Eng! 45: , Cox AG, Bond MR: Bowel habit after vagotomy and gastrojejunostomy. Br Med J 1: , Dragstedt LR, Harper PV Jr, Tovee EB, et a!: Section of the vagus nerves to the stomach in the treatment of peptic ulcer. Complications and end results after four years. Ann Surg 126: , Johnston D, Humphrey CS, Walker BE, et a!: Vagotomy without diarrhoea. Br Med J 3: , Humphrey CS, Johnston D, Walker BE, et a!: Incidence of dumping after truncal and selective vagotomy with pyloroplasty and highly selective vagotomy without drainage procedure. Br Med J 3: , Kennedy F, MacKay C, Bedi BS, eta!: Truncal vagotomy and drainage for chronic duodenal ulcer disease: a controlled trial. Br Med J 2:71-75, Postlethwait RW, Kim SK, Dillon ML: Esophageal complications of vagotomy. Surg Gynecol Obstet 128: , Kennedy T, Connell AM, Love AHG, et a!: Selective or truncal vagotomy? Five-year results of a double-blind, randomized, controlled trial. Br J Surg 60: , Wheldon EJ, Venables CW, Johnston IDA: Late metabolic sequelae of vagotomy and gastroenterostomy. Lancet 1: , Inberg MV, Vuorio M: Human gallbladder function after selective gastric and total abdominal vagotomy. Acta Chir Scand 135: , Visick AH: A study of the failures after gastrectomy. Ann Roy Coli Surg Eng! 3: , Hoerr SO: Evaluation of vagotomy with gastroenterostomy performed for chronic duodenal ulcer. Report based on five-year follow-up of 145 patients. Surgery 38: , Hayden WF, Read RC: A comparative study of the Heinecke-Mikulicz and Finney pyloroplasty. Am J Surg 116: , Payne RA, Wighton R, Bluhm M: Evaluation of drainage procedures combined with vagotomy. Proc Roy Soc Med 63: , Hollander F: Laboratory procedures in the study of vagotomy (with particular reference to the insulin test). Gastroenterology 11: , Ross B, Kay AW: The insulin test after vagotomy. Gastroenterology 46: , Dignan AP: A laboratory appraisal of the effects of truncal and selective vagotomy. Br J Surg 57: , Gillespie G, Elder JB, Gillespie IE, et a!: The long term stability of the insulin test. Gastroenterology 58: , Kronborg 0: The stability of the insulin test result after truncal vagotomy and drainage for duodenal ulcer. Scand J Gastroenterol 6: , Watkin DFL, Duthie HL: Changes in the postoperative insulin test in relation to recurrent duodenal ulceration. Gut 12: , Smith IS, Gillespie G, Elder JB, et al: Time of conversion of insulin response after vagotomy. Gastroenterology 62: , Grossman MI: Insulin test results should be expressed as a number, not as positive or negative. Gastroenterology 63:1089, Fawcett AN, Johnston D, Duthie HL: Revagotomy for recurrent ulcer after vagotomy and drainage for duodenal ulcer. Br J Surg 56: , Johnston D, Thomas DG, Checketts RG, et a!: An assessment of postoperative testing for completeness of vagotomy. Br J Surg 54: , Eisenberg MM, Woodward ER, Carson TJ, eta!: Vagotomy and drainage procedure for duodenal ulcer: the results of ten years' experience. Ann Surg 170: , Gillett DJ, de Burgh MM: Recurrent ulceration after gastroenterostomy or pyloroplasty with complete and incomplete vagotomy. Am J Surg 127: , Watkin DFL: The delayed insulin test and recurrent duodenal ulceration. Br J Surg

13 June 1975 PROGRESS IN GASTROENTEROLOGY : , Kronborg 0: The value of the insulin test in predicting recurrence after vagotomy and drainage for duodenal ulcer. Scand J Gastroenterol 6: , Kronborg 0: Influence of the number of parietal cells on risk of recurrence after truncal vagotomy and drainage for duodenal ulcer. Scand J Gastroenterol 7: , Kronborg 0: A follow-up of patients operated upon for recurrence after vagotomy and drainage for duodenal ulcer. Scand J Gastroenterol 8: , Johnston D, Goligher JC: The influence of the individual surgeon and of the type of vagotomy upon the insulin test after vagotomy. Gut 12: , Grassi G, Orecchia C: A comparison of intraoperative tests of completeness of vagal section. Surgery 75: , Alexander Williams J: The current use of vagotomy in the treatment of peptic ulceration. Br J Surg 56: , Alexander Williams J: How to be an adequate vagotomist. Surgery 75: , Jackson RG: An anatomic study of the vagus nerves, and a technic of transabdominal gastric vagus resection. Bull Michigan Univ Hosp 13: 31-35, Moore FD: Follow-up of vagotomy in duodenal ulcer. Gastroenterology 11: , Franksson C: Selective abdominal vagotomy. Acta Chir Scand 96: , Griffith CA, Harkins HN: Selective gastric vagotomy: physiologic basis and technique. Surg Clin North Am 42: , Griffith CA, Leyse RM, Davis DR, et al: Mortality and recurrent ulcer after selective vagotomy plus pyloroplasty. Am Surgeon 38: , Amdrup E, Jensen H-E: One hundred patients five years after selective gastric vagotomy and drainage for duodenal ulcer. Surgery 74: , DeMiguel J: Late results of bilateral selective vagotomy and pyloroplasty for duodenal ulcer: 5-9 year follow-up. Br J Surg 61: , Kronborg 0, Malmstrom J, Christiansen PM: A comparison between the results of truncal and selective vagotomy in patients with duodenal ulcer. Scand J Gastroenterol 5: , Kennedy T, Johnston GW, Love AHG, et a!: Pyloroplasty versus gastrojejunostomy. Results of a double-blind, randomized, controlled trial. Br J Surg 60: , Kennedy T, Connell AM: Selective or truncal vagotomy? A double-blind randomised controlled trial. Lancet 1: , Sawyers JL, Scott HW Jr, Edwards WH, eta!: Comparative studies of the clinical effects of truncal and selective gastric vagotomy. Am J Surg 115: , Farmer DA, Howe CW, Porell WJ, et a!: The effect of various surgical procedures upon the acidity of the gastric contents of ulcer patients. Ann Surg 134: , Harkins HN, Schmitz EJ, Harper HP, eta!: A combined physiologic operation for peptic ulcer (partial distal gastrectomy, vagotomy and gastroduodenostomy). A preliminary report. Western J Surg 61: , Herrington JL Jr, Edwards LW: Vagotomy and antral resection in the treatment of duodenal ulcer. J Tennessee State Med Assoc 46: , Hoerr SO, Ward JT: Late results of three operations for chronic duodenal ulcer: Vagotomy-gastrojejunostomy, vagotomy-hemigastrectomy, vagotomy-pyloroplasty. Interim report. Ann Surg 176: , Thoroughm:an JC, Walker LG Jr, Raft D: A review of 504 patients with peptic ulcer treated by hemigastrectomy and vagotomy. Surg Gynecol Obstet 119: , Palumbo LT, Sharpe WS, Lulu DJ, eta!: Distal antrectomy with vagotomy for duodenal ulcer. Sixteen-year review of our results in 510 cases. Arch Surg 100: , Wolf JS, Bell CC Jr, Zimberg YH: Analysis of 10 years' experience with surgery for peptic ulcer disease. Am Surgeon 38: , Herrington JL Jr, Sawyers JL, Scott HW Jr: A 25-year experience with vagotomy-antrectomy. Ann Surg 106: , Forrest APM: The treatment of duodenal ulcer by gastroenterostomy, gastroenterostomy and vagotomy and partial gastrectomy. Gastroenterologia 89: , Howard RJ, Murphy WR, Humphrey EW: A prospective randomized study of the elective surgical treatment for duodenal ulcer: two- to ten-year follow-up study. Surgery 73: , Irani FA, Berkas E, Steiger Z: Evaluation of surgical treatment for duodenal ulcer. A prospective randomized study. Am J Surg 122: , Sawyers JL, Scott HW Jr: Antrectomy or pyloroplasty? A prospective study with selective gastric vagotomy. Southern Med J 66:98-101, Cox AG: Comparison of symptoms after vagotomy with gastrojejunostomy and partial gastrectomy. Br Med J 1: , Griffith CA, Harkins HN: Partial gastric vagotomy: an experimental study. Gastroenterology 32:96-102, Holle VF, Hart W: Neue wege der chirurgie des

14 1628 PROGRESS IN GASTROENTEROLOGY Vol. 68, No.6 gastroduodenalulkus. Med Klin 62: , Johnston D, Wilkinson AR: Highly selective vagotomy without a drainage procedure in the treatment of duodenal ulcer. Br J Surg 57: , Amdrup E, Jensen H-E: Selective vagotomy of the parietal cell mass preserving innervation of the undrained antrum. A preliminary report of results in patients with duodenal ulcer. Gastroenterology 59: , Johnston D, Lyndon PJ, Smith RB, et al: Highly selective vagotomy without a drainage procedure in the treatment of haemorrhage, perforation, and pyloric stenosis due to peptic ulcer. Br J Surg 60: , Johnston D, Goligher JC, Pulvertaft CN, et al: The two- to four-year clinical results of highly selective vagotomy (parietal-cell vagotomy) without a drainage procedure for duodenal ulcer. Gut 13:842, Newcombe JF: Fatality after highly selective vagotomy. Br Med J 1:610, Goligher JC: An overall view of the surgical treatment of duodenal ulcer. Adv Surg 8:1-27, Moberg S, Hedenstedt S: Selective proximal vagotomy. A three year follow-up. Scand J Gastroenterol 8(suppl 20): 9, Madsen P, Kronborg 0: A double-blind trial of highly selective vagotomy without drainage and selective vagotomy with pyloroplasty in the treatment of duodenal ulcer. Scand J Gastroenterol 8(suppl 20): 12-13, Wastell C, Colin JF, MacNaughton JI, et al: Selective proximal vagotomy with and without pyloroplasty. Br Med J 1:28-30, Liedberg G, Oscarson J: Selective proximal vagotomy-short time follow-up of 80 patients. Scand J Gastroenterol 8(suppl 20): 12, Korman MG, Hansky J, Coupland GAE, et al: Gastrin studies after parietal cell vagotomy. Is drainage necessary? Digestion 8:1-7, Stadil F, Rehfeld JE: Gastrin response to insulin after selective, highly selective, and truncal vagotomy. Gastroenterology 66:7-15, Jaffee BM, Clendinnen BG, Clarke RJ, et al: Effect of selective and proximal gastric vagotomy on serum gastrin. Gastroenterology 66: , Kragelund E, Fischer JE, Nielsen A: Meat extract-stimulated gastric acid secretion before and after parietal cell vagotomy without antrum drainage and selective gastric vagotomy with drainage in patients with duodenal ulcer. Ann Surg 179: , Wilkinson AR, Johnston D: Effect of truncal, selective and highly selective vagotomy on gastric emptying and intestinal transit of a foodbarium meal in man. Ann Surg 178: , 1973