Ulcer Surgery and Highly Selective Vagotomy—Y2K

WHILE ulcerations of the stomach and duodenum remained common entities in the latter half of the 20th century, the number of operations performed for ulcer declined remarkably. Medical treatments became effective as specific medications (the histamine-receptor antagonists and proton-pump inhibitors [PPIs]) eliminated the deleterious effects of intraluminal acid, greatly reducing the need for operations.¹ Subsequently, bacterial infection was proven to be a major risk factor for gastric and duodenal ulcers, especially for ulcer recurrence, which was eliminated in 98% of those at risk by antibiotics directed against Helicobacter species.^{2 - 3} For the first time in history, medical treatments for ulcer were clearly more effective than ulcer operations; ulcer surgery, once the only "definitive" therapy, is perceived as a heroic intervention, reserved for patients without other alternatives.

In the past 2 decades the advantages of highly selective vagotomy (HSV) in treating ulcers have been widely recognized; HSV is synonymous with parietal cell vagotomy or proximal gastric vagotomy. The avoidance of postoperative complications, the main advantage of HSV, was an especially compelling point for those surgeons who had encountered many patients treated with alternative operations.⁴ Because few patients receive operations for ulcer, postgastrectomy complaints are rarely encountered by surgeons in training and the benefits of an operation such as HSV may not be apparent. If a patient with crippling symptoms is encountered, however, there is usually no successful remedy; for that reason, and because elective ulcer surgery is sometimes necessary in any medical setting, I am convinced that experienced surgeons should make an effort to preserve the HSV. In view of the decreasing numbers of operations, the challenge we must address is substantial: to preserve this attractive surgical treatment for patients with ulcers, and to ensure that surgical trainees continue to learn how to perform it.

Surgeons have debated the pros and cons of various surgical treatments for decades, just as surgical trainees have studiously compared the technical aspects of the operations for ulcer. Gastric resection according to Billroth and Polya, vagotomy according to Dragstedt, and pyloroplasty in the manner of Mikulicz and Rydigier have been a standard part of this curriculum, as described by Wangensteen et al.⁵ These operations, especially partial or subtotal gastrectomy, are effective in curing ulcers, but have an unavoidable risk of postoperative complications (ie, diarrhea, bilious vomiting, early dumping, and others) in a variable minority of patients. Surgeons in the past viewed these complications as an unavoidable but necessary risk, while physicians and patients generally viewed surgical intervention as a last resort. The postgastrectomy patient with incapacitating digestive problems was encountered in every gastrointestinal clinic (about 1.0% of the patients who underwent gastrectomy). These individuals were notorious for their many and varied symptoms, and gastrectomy achieved the dubious status as both a treatment (of ulcer) and a cause of chronic complaints (labeled "postgastrectomy syndrome") in the medical community at large.

Since the turn of the century, as the aphorism "No acid, no ulcer" suggests, medical treatments consisted of a variety of regimens, including dietary recommendations, sedatives, anticholinergics, antacids, and topical agents aimed at either neutralizing or decreasing the amount of acid secreted by the stomach, or protecting the mucosa from the injurious effects of acid. When the histamine-receptor antagonists were reported in the mid 1970s, surgical procedures were the only effective treatment for the serious ulcer complications (eg, bleeding, perforation, or obstruction [in decreasing order of occurrence]), and were applied to patients who had failed to achieve cure with the nonspecific medical remedies of the day. Thereafter, and continuing to the present, only perforation was generally accepted as an indication for surgery.

The discovery and introduction of drugs targeting the histamine₂-receptors of gastric parietal cells (H₂-receptor–blocking agents) allowed patients to postpone surgery for severe ulcer indefinitely, since most of their symptoms disappeared after treatment. Even gastrinoma-associated ulcers, which were commonly 2 to 4 cm in diameter and prone to recur within days of discontinuing medication, were effectively treated by H₂-receptor blockers. Control of acid secretion in the true "hypersecretors" was achieved by titrating the dose of medicine according to hourly gastric secretion. Subsequently, PPIs were introduced, with the major advantages of once-daily dosing for most patients and nearly complete elimination of intraluminal acid from the stomach and duodenum. While PPIs abolished almost all ulcer symptoms, ulcer recurrences remained a major problem, affecting almost 100% of treated patients within 12 to 24 months of initial treatment if medication was discontinued abruptly or completely.^{1 - 3 ,6}

The importance of maintenance therapy for ulcers was conceived and widely accepted; the operational concept was that patients with an ulcer had a predilection for ulcer ("the ulcer diathesis"). The essence of this elusive condition was an imbalance between mucosa-aggressive factors (notably, increased acid and pepsin production) and mucosa-protective factors (adequate blood flow, growth factors, and other constitutive parts of the healing process) that enhance mucosal integrity and mediate the repair of mucosal defects. This concept of ulcer pathogenesis, extant for almost 100 years, has been reevaluated following the recent discovery of the importance of a bacterial species, Helicobacter pylori, as a cofactor in ulcer pathogenesis.

In 1985 the association between H pylori infections and ulcerations of the stomach was discovered.^{6 - 7} The importance of the H pylori infection in ulcer had not been recognized previously, but after the discovery of this association, it was recognized that eradication of the bacterial infection prevented the high recurrence rates that had complicated previous anti-ulcer treatment regimens. The role of the H pylori infection in the ulcer equation is, however, complex. As many as 50% of unselected individuals in the community may be infected with Helicobacter species, but do not have an ulcer; however, most patients with an ulcer will have H pylori infection.¹ At the 1994 NIH (National Institutes of Health) Consensus Conference on the medical treatment of ulcer, the optimal treatment of ulcer was defined as combination therapy consisting of PPIs or histamine₂-receptor blockers and broad-spectrum antibiotics; prescribing patterns have been changed in many communities, as a direct result, although there is still substantial room for improvement in some communities.⁸

These discoveries have had a revolutionary effect on the previous concepts about acid secretion and ulcers. Previously, vagus nerve hyperactivity had been defined as a cause of increased acid secretion following the work of Dragstedt and others at the University of Chicago, Chicago, Ill, who demonstrated that patients with ulcers typically secreted acid continuously, as opposed to the "normal" triphasic pattern (cephalic, gastric, and intestinal phases) of secretion. Subsequently, systematic physiological studies of patients who completed ulcer therapy that included antibiotics have established that an abnormal pattern of acid secretion is no longer present. The intense acid secretion characteristic of patients with an ulcer appears to have been due to a defect in the autoregulation of acid secretion, including changes in antral gastrin and somatostatin release. Antral gastrin is a natural stimulant of acid secretion; normally gastrin levels fall after acidification of the gastric antrum due to several mechanisms including antral D-cell somatostatin release. Helicobacter-infected antral cells exhibit up-regulated gastrin release and down-regulated somatostatin release. Thus, the excessive production of acid and gastrin that had been thought an immutable and inherently damaging part of the "ulcer complex" is now defined as a reversible manifestation of Helicobacter species infection. As the H pylori infection is controlled, gastrin and somatostatin metabolism and the pattern of acid secretion return to normal.^{9 - 10}

Until the reintroduction of vagotomy in Chicago in 1943, gastric resection was the operation of choice for ulcer, and was highly effective for curing ulcers; the only problems with gastrectomy were the seemingly unavoidable incidence of postoperative mortality and morbidity. A mortality rate of 1% to 3% is not alarmingly high, but when combined with morbidity rates of 15% to 20% was sufficient incentive for surgeons to pursue surgical alternatives to gastric resection. The "new" procedure of truncal vagotomy (TV) was rarely associated with mortality and was adopted with enthusiasm by many surgeons. The major weakness of TV was the high (10%) risk of recurrent ulceration.

When TV was combined with a limited gastrectomy, the recurrent ulcer problem disappeared; the search for the "criterion" standard in ulcer surgery seemed to have ended. The TV antrectomy, referred to as the "belt-and-suspenders" procedure for ulcers, was rarely complicated by ulcer recurrence or mortality (0.5%-1.0% risk for either complication). Unfortunately, postoperative symptoms were still problematic, leading to the development and testing of the physiological operation for ulcer—HSV.

Highly selective vagotomy was developed in the University of Washington, Seattle, and decreased gastric acid secretion by 70%¹¹ ; since it was performed without the need for opening the gastrointestinal tract (eg, pyloroplasty), infectious complications were rarely seen. Other side effects, including diarrhea, bilious vomiting, early dumping syndrome, and others were almost completely eliminated. Because HSV caused few postoperative side effects and had almost no risk of mortality, it became the operation of choice in many clinics worldwide. In the United States, however, surgeons did not fully embrace this operation that was not as effective as the TV-antrectomy in curing ulcers.

Highly selective vagotomy was first performed in the United States in 1968 at the University of Illinois, Chicago. Early reports (before 1975) showed high recurrence rates (up to 25%); later studies showed an average 10% recurrence rate with HSV, although some reports, including our own, had lower rates (2% recurrence).^{12 - 15} Just as the operative results were improving, the world of ulcers changed remarkably; the coincidence of natural factors and effective medical treatments alluded to previously were eliminating the need for ulcer surgery.¹ The question for surgeons and surgeon-educators, therefore, has become: "Have all of the discoveries about HSV become irrelevant in a world in which operation is so rarely performed?"

In 1995, 4 million individuals visited physicians for problems caused by a peptic ulcer.¹⁶ Judging by hospital discharge data, the incidence of duodenal ulcers has gradually decreased, while that of gastric ulcers has remained constant or increased for the past 20 years.^{1 ,16 - 18} Ulcer complications (Figure 1), including death, have diminished markedly in the United States, with the greatest decreases noted in the first part of the 20th century. Despite these decreases, the mortality from perforation and hemorrhage has been constant or increased; the overall effect of medical treatment per se, therefore, can be interpreted in several ways. Some have suggested that the overall success of medical treatment has been associated with a shift to the right for age groups that experience hemorrhage and perforation.^{19 - 21} The epidemiological data from Western Europe are of particular interest because they are derived from well-defined cohorts with almost 100% follow-up within the purview of comprehensive national health services. As a result, the information they report provides useful insights regarding the incidence of common medical and surgical conditions.

In Denmark and Finland recently the mortality from perforation and hemorrhage increased dramatically (a 2-fold increase in Finland, and 20% increase in Denmark); during the same interval, there was a decrease in the hospitalization rate in Denmark. In both countries the increased mortality was particularly evident in elderly people.^{19 - 21} Patients older than 65 years had a 4-fold increase in the number of hospital discharges compared with patients younger than 65 years, and a progressively higher death rate with each decade of life (death rate >80 per 100,000 persons in patients older than 85 years²¹ ).

These data mirror some aspects of the ulcer problem in the United States, where overall deaths have decreased, but older patients have a high (and ever-increasing) risk for ulcer complications.¹⁸ The incidence of hospitalization for ulcer problems in the United States as estimated by National Hospital Discharge Survey has also continued to decrease for the past 2 decades; while this is heartening, the ulcer problem accounted for more than 2 million discharges per year as recently as 1996.¹⁷ Similarly as in Scandinavia, older Americans are especially vulnerable to complications, which have increased with regularity in those older than 65 years (Figure 2) .¹⁷ Whether more uniform application of the latest treatments can improve these results is unknown.^{8 ,17 ,22}

As medical treatments became increasingly more effective, ulcer complications such as perforation and pyloric stenosis, which result from months or years of continuous peptic activity, did not develop. The severely scarified duodenal bulb, the stenotic gastric duodenal outlet, and other manifestations of advanced ulcers, once commonly encountered on busy hospital wards, are rarely (if ever) seen. Medical students in some schools may now finish an entire clerkship in medicine or surgery without once caring for a patient with peptic ulcer disease. What a profound change from 1975, when every medical or surgical ward had at least one patient with a severe ulcer complication. Who would have predicted such a thing in 1975?

In 2000 and thereafter, there will be some patients who will require surgical treatment. Older patients who have had previous scarification of the duodenal bulb or gastric outlet may still have episodic bleeding, perforation, or obstruction of the gastric outlet, including some who are "Helicobacter negative." Since bleeding is routinely controlled by endoscopic therapy or embolization, few patients require emergent operation; after the patient has been stabilized, and after bleeding has been controlled by endoscopic means, discussions of surgical intervention can be made on an elective basis. Surgeons should have a place in discussions regarding the "best" approach since they understand the totality of possible approaches.

Graduating chief residents in surgery in the United States have performed (on average) less than 1 HSV during their residency (1997 Surgical Operative Log Data, compiled by the Residency Review Committee for Surgery under the Accreditation Committee for Graduate Medical Education). The average number of all types of vagotomy for graduating chief residents was 3.5, including 3.2 TVs, and 0.3 HSV procedures. Because residents may never see an HSV performed during their residency, it is possible that HSV, once in the mainstream of surgery, will remain trapped in the backwater of infrequently practiced operations. After a few years in this dubious status, HSV, once on the cutting edge of surgery and of such importance in the world of peptic ulcer surgery, will be obsolete.

Recently there has been a marked increase in the number of minimally invasive operations performed for gastroesophageal reflux disease. The increased incidence is not well understood, including the phenomenon whereby gastroesophageal reflux disease develops in the aftermath of successful medical treatment for ulcer disease. Surgeons' familiarity with laparoscopic fundoplication has set the stage for further application of HSV, which requires similar attention to the anatomy of the esophageal hiatus and the relationships of the crura of the diaphragm with the branches of the vagus nerve trunks. The modern operative techniques such as Harmonic scalpel and bipolar scalpel dissection, which simplified the performance of laparoscopic fundoplication, have also simplified the performance of HSV.^{22 - 26}

As it happens, laparoscopic fundoplication includes dissection of several areas that are part of the operative dissection required for HSV.²⁷ Therefore, those surgeons interested in HSV have already performed at least half of the operation already; for the remaining parts of the procedure, reference to the publications already cited will provide the necessary information and diagrams. Thus, there is a convenient solution to the question about younger surgeons having an opportunity to learn this operation. Since operations for gastroesophageal reflux are on the rise and since the younger surgeons are becoming highly proficient in the finer points of periesophageal and esophageal hiatus anatomy, they have already accomplished a large part of the learning curve.²⁷

If operation is required for patients with an ulcer, vagotomy of some type will be part of the treatment; HSV provides the best overall operative treatment, and can be safely performed in most patients, excluding only those who are unstable or have severe concomitant medical conditions which preclude the extra time (approximately 30-45 minutes) required for its performance.

While the role of open operations for ulcer complications is well established, there is little doubt that laparoscopic approaches will increase in popularity for appropriate candidates. Because practicing surgeons prefer to perform operations that they have performed for years and because there is a diminishing incidence and prevalence of ulcer in most areas of the world, surgeons who are interested in practicing HSV must make an effort to preserve it. If we continue to consider the merits of this operation compared with alternatives, HSV will always have a well-deserved place among surgical options.

Corresponding author: Philip E. Donahue, MD, Division of General Surgery, Cook County Hospital, 1835 W Harrison St, Room 6429, Chicago, IL 60612 (e-mail: phil@eolas.com).