1696
SELECTED SUMMARIES
GASTROENTEROLOGY
ical quality, most of the studies which follow patients after treatment for a year or more indicate that only 0%-4% of patients with eradication develop duodenal ulcer recurrence [Med J Aust 1990; 153:145-149; Lancet 1990;335:1233-1235; Med J Aust 1989151: 431-435; Gastroenterology 1991;100:A104 (abstract); Gastroenterology 1992;102:A118 (abstract); Gastroenterology 1990;98:A104 (abstract); Gastroenterology 1988:94:A431 [abstract)]. Two other studies reported rates of ulcer recurrence of l/10 (10%) (Lancet 1987;2:1109-1111) and 5/24 (21%) (Lancet 1988;2:1437-1442). Graham et al. found that all 3 H. pylori-negative patients with recurrent duodenal ulcers in their study were ingesting NSAID’s; apparently no other patient with H. pylori eradication had an ulcer recurrence. Graham et al. also have provided, for the first time, evidence that gastric ulcer recurrence is similarly decreased by H. pylori eradication. None of their gastric ulcer patients in whom H. pylori was eradicated had a recurrence. A recent abstract also reported that O/10 patients with H. pylori eradication had gastric ulcer relapse compared with 24/42 who wereH. pylori-positive [Gastroenterology 1992;102:A162 (abstract)]. How should the studies by Graham and others affect clinical practice? The answer ranges from “do not treat any patient for H. pylori until further information is available” to “treat all patients who have an ulcer not associated with NSAID ingestion”. I feel that standard ulcer therapy is still the treatment of choice for the first episode of peptic ulcer disease. H. pylori therapy may be useful for ulcers refractory to standard therapy but refractory ulcers should be extremely rare with potent antisecretory agents such as omeprazole. Patients with recurrent ulcers on maintenance therapy definitely should be considered for H. pylori therapy. A more difficult question is whether H. pylori therapy should now be used instead of maintenance therapy for patients with recurrent ulcers. We need to be certain that the side effects of one-time H. pylori treatment are not worse and more costly than intermittent or maintenance therapy with HZ-antagonists. Another important variable is the rate of reinfection; a high rate of reinfection might argue against the utility of H. pyIori therapy. The rates of reinfection in the United States and northern Europe are probably low [perhaps 1% a year), but reinfection may be much higher in other geographic locations and ethnic groups. The idea of treating patients who have had ulcer complications such as bleeding is an attractive one. However, prospective studies must document that not only ulcers but complications of ulcers are decreased by H. pylori eradication. Graham’s group recently presented an abstract that examined the subset of patients in their long-term study who initially presented with bleeding [Gastrointest Endosc 1992;38:234 (abstract)]. Patients given triple therapy had fewer ulcer recurrences (18% vs. 43%) and significantly fewer rebleeding episodes (0 vs. 29%) during a follow-up of just under 1 year. Many questions regarding H. pylori therapy remain. We need to define the most effective treatment regimen with the fewest side effects. At present the standard combination is a bismuth compound plus 2 antibiotics (probably metronidazole and amoxicillin or tetracycline), although 2 antibiotics alone may give similar rates of eradication (Lancet 1989;1:690-692; Gastroenterology 1992;102:A58). In the future we also need to explore the role of newer antibiotics and determine what regimen to use in patients who fail initial therapy. L. LAINE. M.D.
WHAT IS INTENSIVE GASTROESOPHAGEAL
THERAPY REFLUX?
FOR
SJ, Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group (Department of Veterans
Spechler
Vol. 103,No. 5
Affairs Medical Research Service Cooperative Studies Program). Comparison of Medical and Surgical Therapy for Complicated Gastroesophageal Reflux Disease. N Engl J Med 1992;326:786-792. Of all the acid-related disorders afflicting humans, gastroesophageal reflux disease (GERD) is certainly the most prevalent. Heartburn, its cardinal symptom, is experienced by the vast majority of adult Americans at some point during their lifetime, and approximately 40% of Americans have heartburn at least once each month. Although the majority of these individuals do not seek medical attention, IO%-26% of those who do will develop serious complications of chronic reflux, including erosive esophagitis, peptic esophageal strictures, and metaplasia (Barrett’s esophagus). Despite the chronicity of this disorder, prior studies evaluating various therapeutic modalities for severe GERD were short term, with few lasting more than 12 weeks. Moreover, most trials evaluated only one form of therapy, usually a specific antisecretory or prokinetic agent or surgical fundoplication. This study by Spechler et al. represents the first attempt to examine and compare long-term conventional medical and surgical therapy in a large group of patients with complicated GERD. Patients included in this multicenter trial were identified by clinical records, as well as reviews of barium esophagrams and esophagogastroduodenoscopic (EGD) examinations. Inclusion criteria included the presence of peristaltic contractions during esophageal manometry and endoscopic or histological evidence of esophagitis. In addition, gastroesophageal reflux was detected in each patient by the use of 24-hour esophageal pH monitoring. Twohundred forty seven patients (98% men) were randomized by computer to one of three treatment groups: (a) continuous medical therapy, (b) symptomatic therapy, and (c) surgical therapy consisting of a Nissen fundoplication. The three treatment groups did not differ with regard to age, lower esophageal sphincter (LES) pressure, episodes of reflux, the histological grade of esophagitis, or the presence of esophageal ulcers, strictures, and Barrett’s esophagus. Furthermore, the GERD activity index, a standardized system for scoring clinical activity, was nearly identical for each randomized treatment group before the institution of therapy. General antireflux maneuvers were prescribed for all patients and included elevation of the head of the bed, the avoidance of medication known to decrease LES pressure, and the prohibition of smoking, alcohol, bedtime snacks, and foods known to precipitate heartburn in individual persons. In addition, all patients were permitted the use of antacid tablets as needed and esophageal dilation as needed for dysphagia. Patients in group one were given antacid tablets after meals and ranitidine, 150 mg, twice daily. For persistent symptoms, metoclopramide, 10 mg four times daily, was added, and for those patients unresponsive to these medications a sucralfate slurry was included in the regimen. Group two patients were treated symptomatically only in a stepwise fashion, starting with antacid tablets and progressing to ranitidine, metoclopramide, and finally sucralfate as needed to alleviate heart-
November 1992
burn. In the final group of patients, a Nissen fundoplication was performed, after which no antireflux medication was administered. Patients were evaluated every 3 months for symptoms, adverse events, and compliance, and the GERD activity index was calculated. Six weeks after beginning therapy and every year thereafter, patients underwent esophageal manometry, barium esophagram, EGD, and Z&hour pH monitoring studies, and the objective parameters indicated previously were assessed. Follow-up data were available for 176 patients at 1 year and for 106 patients at 2 years. The mean GERD activity index score improved significantly in all three treatment groups: from 108 to 87 in group 1 (continuous medical therapy), from 107 to 88 in group z (symptomatic therapy), and from 109 to 78 in group 3 (surgical group). The histological grade of esophagitis decreased significantly in their respective groups from 2.9 to 2.0, from 2.9 to 2.3, and from 2.9 to 1.4. Improvements in both the mean GERD activity index score and histology were significantly better in the surgically treated group of patients than in either group treated medically. Furthermore, patient satisfaction was significantly greater in the surgical group of patients than in either medical group, and more treatment failures occurred in groups one and two than in patients who underwent Nissen fundoplication. Finally, no operative or perioperative deaths occurred, and the frequency of adverse effects of therapy was similar in all three groups. Based on the results of the trial, the authors conclude that in men with complicated GERD, although medical therapy is effective, operative fundoplication is significantly superior in improving symptoms associated with the disofder and in improving the endoscopic signs of esophagitis. GERD is an extremely common, chronic condition with a wide spectrum of manifestations, of which heartburn is the most common. According to a recent poll (Gallup Organization, 1988), heartburn occurs daily in 14% and at least once monthly in 44% of adult Americans. The majority of these individuals have only mild and sporadic symptoms that are controlled with overthe-counter preparations, such as antacids, and these persons rarely otherwise seek medical attention. Those persons with more severe and persistent symptoms often will obtain the advice of a physician. However, the majority of these patients will be found to have nonerosive GERD on endoscopic evaluation. Only lO%20% of those who seek medical attention will develop serious complications of chronic reflux, which include erosive esophagitis, peptic esophageal strictures, Barrett’s esophagus, and tracheopulmonary aspiration (Arch Intern Med 1991;151:448-454). Effective therapy for GERD is based on a thorough understanding of the pathophysiology and natural history of the disease. The pathophysiological mechanisms involved are primarily motor in nature and include inappropriate relaxations of the LES, inadequate esophageal clearance of refluxed materials, and delayed gastric emptying (Ann Intern Med 1982;97:93-103). The first stage of therapy involves lifestyle modifications and consists of either elevating the head of the bed or the use of a wedge that elevates the patient’s entire thorax, weight loss, avoidance of tight-fitting garments, decreasing the size and composition of meals, and abstinence from known precipitants of gastroesophageal reflux. Such suggestions are often met with resistance by patients who more often than not prefer a prescription that will enable them to enjoy the lifestyle they have chosen to lead.
Comment.
SELECTED SUMMARIES 1697
Despite improvements in our understanding of the disorder and the availability of prokinetic medications that correct motor abnormalities, the use of these drugs as single agents for the treatment of GERD has been largely disappointing. The pathogenesis of GERD does involve disturbances in normal gastroesophageal motility; however, the symptoms and complications of GERD occur as a result of the acidic material being refluxed. Although mean basal gastric acid secretion in patients with GERD is either normal (Gastroenterology 1991;101:1149-1158) or minimally elevated (Gastroenterology 1992;102:2182-2183), the use of drugs that either neutralize gastric acidity or block hydrogen ion generation or secretion has historically comprised the foundation of medical therapy. Antacids and compounds containing alginic acid are very useful for those patients with mild, uncomplicated episodic heartburn. However, owing to their short duration of action, symptom relief may be transient, necessitating the use of repeated doses of these drugs. Furthermore, the relief of nocturnal symptoms is often unsatisfactory, and the use of repeated doses of highpotency antacids may precipitate diarrhea. Histamine HZ-receptor antagonists have become the mainstay of therapy for GERD. However, several unresolved issues remain regarding their optimal use in the disorder, many of which are exemplified in this study by Spechler et al. As indicated previously, GERD is a disorder characterized by a wide spectrum of clinical severity. HZ-antagonists are often not as useful as antacids in patients with mild episodic heartburn owing to their delayed onset of action. In contrast, the HZ-receptor antagonists are very effective in alleviating symptoms in most patients with frequent, recurrent episodes of heartburn who require medication on a daily basis. However, what is the optimal dose of HZ-blockers, and what is the proper dosing interval for these drugs? The answer to these questions relies on the recognition that GERD and duodenal ulcer disease represent different entities, a perception that is unfortunately often disregarded by many physicians and licensing agencies. The latter disorder is generally characterized by exacerbations of disease activity lasting for several weeks, followed by remissions of various duration. Patients with active duodenal ulcer can be treated with HZ-receptor antagonists, which, when given in a single nocturnal dose over a 4-week period, will heal approximately 75%-85% of ulcers. Moreover, maintenance therapy for duodenal ulcer, consisting of nocturnal, lowdose HZ-receptor blockade, is highly effective in preventing ulcer recurrence. In contrast, GERD is a chronic disorder that requires long-term therapy in most individuals. Often, the medical regimen that alleviates symptoms or controls complications is the one that will be required to maintain a patient in remission for weeks, months, or, at times, years. The treatment of GERD should be individualized to the severity of patients’ symptoms and the degree of esophagitis and other complications of acid reflux. Many. if not most, patients with nonerosive GERD who require continuous therapy can be managed with an HZ-blocker, given in two daily doses, as was done in this report by Spechler et al. However, as was also shown in this study, many individuals with complicated GERD do not respond to such a drug regimen but rather require “intensive therapy.” What is the definition of “intensive medical therapy” and what is the role of surgical intervention for patients with GERD? As shown in this study, the results of surgery can be quite gratifying and may often enable patients to significantly improve their quality of life. In addition, owing to the chronic nature of this disorder, antireflux surgery may represent the most cost-effective means of therapy in young patients faced with the prospect of life-longmedical therapy. However, antireflux surgery is generally reserved today for patients who are refractory to medical therapy, who are noncompliant, or who have intolerable complications of GERD, such as continued tracheopulmonary aspiration. Unfortunately, a clear definition of intensive therapy cannot be deduced from the
1698
SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 103, No. 5
present report. Although this was a carefully designed and extensive study, Spechler et al. did not foresee the relatively recent evolution in medical therapy for this chronic disorder. An intensive medical regimen was employed in this study. However, such a regimen consisting of four different drugs has been obviated by the use of either high doses of HZ-receptor antagonists (Gastroenor the substituted benzimidazole ometerology 1990;98:654-661) prazole (N Engl J Med 1991;324:965-975). Despite this one shortcoming, by virtue of its design, the study by Spechler et al. has provided important information regarding the natural history and appropriate therapy of GERD. As stated previously, it represents the first attempt to examine and compare long-term conventional medical and surgical therapy in a large group of patients with GERD. Furthermore, it shows that an intensive medical regimen can be employed to effectively and safely treat the symptoms of GERD and complications associated with long-standing gastroesophageal reflux of acid. Finally, of utmost importance, the study confirms the necessity to individualize medical therapy according to the requirements of each individual patient. M. M. WOLFE, M.D.
CAN ESOPHAGUS BE BLAMED NONCARDIAC CHEST PAIN?
FOR
Hick DG, Morrison
jFJ3, Casey IF, et al. (Cardiac Research Unit, Killingbeck Hospital, Leeds, England; and the Department of Physiology, University of Leeds, Leeds, England). Oesophageal motility, luminal pH, and electrocardiographic-ST segment analysis during spontaneous episodes of angina like chest pain. Gut 1992;33:79-86.
The esophagus, as the source of noncardiac chest pain, has been extensively studied during the last 10 years. After careful exclusion of cardiac etiology, a significant number of patients are found to have esophageal contraction abnormalities. These esophageal contraction abnormalities are thought to be the cause of chest pain. However, there is a lack of direct correlation between abnormal esophageal contractions and chest pain. The study in review by Hick et al. is another attempt to define the cause and effect relationship between chest pain and the esophagus. These investigators studied 46 patients with anginalike chest pain of >6 months in whom cardiac evaluation, including coronary angiography, was normal. Ambulatory esophageal motility, pH monitoring, and EKG recordings were obtained for 24 hours in the patient’s home environment, and patients were encouraged to pursue those activities known to provoke symptoms.
The pressures were recorded at 5,10, and 15 cm above the upper border of the lower esophageal sphincter (LES) using a solid state transducer system. The esophageal pH was recorded at 7.5 ems above the LES. A thirty-minute period before and a 30-minute period after the occurrence of chest pain was used as a control and compared with the data during pain periods. All of the manometric, pH, and EKG data were analyzed using a software and computer. A standard esophageal motility using infusion manometry and station pullthrough technique was performed before ambulatory recordings in these patients. These manometric data were compared with the control data published in the literature.
The results of the standard motility study show the contraction amplitudes to be somewhat lower in the patient population than controls and the contraction duration to be significantly higher in the patients but only in the distal esophagus. The LES pressure was significantly higher in the patients. There was no distinct contraction abnormality or acid reflux seen during ambulatory studies during 59 pain events in 35 patients. Even though there was no direct temporal correlation between the occurrence of chest pain and the acid reflux events, 70% of the patients showed a pathological degree of reflux on .&hour pH score. Gastroesophageal reflux occurred mostly in the supine rather than upright position. Two episodes of chest pain correlated with EKG changes suggestive of ischemia. Comments. Seven studies of ambulatory esophageal motility and pH recordings have been reported in the recent literature. The intent of these studies was to establish a cause and effect relationship between chest pain and pathological esophageal events such as contraction abnormality and acid reflux. The contraction abnormality was thought to be the cause of chest pain in o%-43% of the instances and acid reflux the cause of chest pain during O%-30% of the events among various studies. Table 1 shows various aspects such as numbers and patient population studied, total number of pain episodes recorded, Bernstein test, 24 hour pH scores and the temporal relationship between chest pain and pathological esophageal event. Studies 2 and 6 in Table 1 reported that in about 30% of the patients either an abnormal esophageal contraction or acid reflux can be documented at the time of chest pain. However, a clear definition of abnormal contraction was not provided in these studies. Studies 5 and 7 (same investigator group) provide the most optimistic figures in terms of identification of a pathological event at the moment of chest pain. The various criteria used by various authors to define an abnormal esophageal contraction and acid reflux are shown in Table 2. Based on these criteria, it is not surprising that different investigators have come up with different numbers. Is one criteria better than the other and what should be the best criteria? It appears that the most rigorous criteria for abnormal contraction and acid reflux was used by Peters et al. (Gastroenterology 1988;94:878886) and they found only a modest temporal relationship between pathological esophageal event and chest pain. Symptom index, defined as the frequency of pain events associated with the pathological events, of greater than 75% has been accepted to establish the cause and effect relationship. A positive symptom index for reflux and contraction abnormality has been reported in up to 43% and 33% of patients respectively. However, if one looks at the frequency of pathological events (abnormal motility and acid reflux) causing chest pain, one finds no relationship. In the absence of a clear temporal association between chest pain and pathological esophageal event, one wonders if the esophagus can really cause chest pain. Provocation of chest pain during Bernstein test and esophageal distension clearly establishes that the esophagus is capable of causing chest pain. Twenty to 70% of patients with chest pain have pathological 24-hour acid reflux scores. It is possible that in some patients acid sensitive receptors in the esophagus interpret the heartburn sensation as chest pain sensation. Clearly these patients respond to antireflux therapy. However, a subgroup of patients, not responsive to antireflux therapy may have an abnormal motility parameter such as longitudinal muscle contraction of the esophagus that cannot be measured by intraluminal pressure measurement technique. This is based on the observation that afferent activity from the tension receptors correlates with the longitudinal rather than circular muscle contraction.
SELECTED SUMMARIES
GASTROENTEROLOGY
ical quality, most of the studies which follow patients after treatment for a year or more indicate that only 0%-4% of patients with eradication develop duodenal ulcer recurrence [Med J Aust 1990; 153:145-149; Lancet 1990;335:1233-1235; Med J Aust 1989151: 431-435; Gastroenterology 1991;100:A104 (abstract); Gastroenterology 1992;102:A118 (abstract); Gastroenterology 1990;98:A104 (abstract); Gastroenterology 1988:94:A431 [abstract)]. Two other studies reported rates of ulcer recurrence of l/10 (10%) (Lancet 1987;2:1109-1111) and 5/24 (21%) (Lancet 1988;2:1437-1442). Graham et al. found that all 3 H. pylori-negative patients with recurrent duodenal ulcers in their study were ingesting NSAID’s; apparently no other patient with H. pylori eradication had an ulcer recurrence. Graham et al. also have provided, for the first time, evidence that gastric ulcer recurrence is similarly decreased by H. pylori eradication. None of their gastric ulcer patients in whom H. pylori was eradicated had a recurrence. A recent abstract also reported that O/10 patients with H. pylori eradication had gastric ulcer relapse compared with 24/42 who wereH. pylori-positive [Gastroenterology 1992;102:A162 (abstract)]. How should the studies by Graham and others affect clinical practice? The answer ranges from “do not treat any patient for H. pylori until further information is available” to “treat all patients who have an ulcer not associated with NSAID ingestion”. I feel that standard ulcer therapy is still the treatment of choice for the first episode of peptic ulcer disease. H. pylori therapy may be useful for ulcers refractory to standard therapy but refractory ulcers should be extremely rare with potent antisecretory agents such as omeprazole. Patients with recurrent ulcers on maintenance therapy definitely should be considered for H. pylori therapy. A more difficult question is whether H. pylori therapy should now be used instead of maintenance therapy for patients with recurrent ulcers. We need to be certain that the side effects of one-time H. pylori treatment are not worse and more costly than intermittent or maintenance therapy with HZ-antagonists. Another important variable is the rate of reinfection; a high rate of reinfection might argue against the utility of H. pyIori therapy. The rates of reinfection in the United States and northern Europe are probably low [perhaps 1% a year), but reinfection may be much higher in other geographic locations and ethnic groups. The idea of treating patients who have had ulcer complications such as bleeding is an attractive one. However, prospective studies must document that not only ulcers but complications of ulcers are decreased by H. pylori eradication. Graham’s group recently presented an abstract that examined the subset of patients in their long-term study who initially presented with bleeding [Gastrointest Endosc 1992;38:234 (abstract)]. Patients given triple therapy had fewer ulcer recurrences (18% vs. 43%) and significantly fewer rebleeding episodes (0 vs. 29%) during a follow-up of just under 1 year. Many questions regarding H. pylori therapy remain. We need to define the most effective treatment regimen with the fewest side effects. At present the standard combination is a bismuth compound plus 2 antibiotics (probably metronidazole and amoxicillin or tetracycline), although 2 antibiotics alone may give similar rates of eradication (Lancet 1989;1:690-692; Gastroenterology 1992;102:A58). In the future we also need to explore the role of newer antibiotics and determine what regimen to use in patients who fail initial therapy. L. LAINE. M.D.
WHAT IS INTENSIVE GASTROESOPHAGEAL
THERAPY REFLUX?
FOR
SJ, Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group (Department of Veterans
Spechler
Vol. 103,No. 5
Affairs Medical Research Service Cooperative Studies Program). Comparison of Medical and Surgical Therapy for Complicated Gastroesophageal Reflux Disease. N Engl J Med 1992;326:786-792. Of all the acid-related disorders afflicting humans, gastroesophageal reflux disease (GERD) is certainly the most prevalent. Heartburn, its cardinal symptom, is experienced by the vast majority of adult Americans at some point during their lifetime, and approximately 40% of Americans have heartburn at least once each month. Although the majority of these individuals do not seek medical attention, IO%-26% of those who do will develop serious complications of chronic reflux, including erosive esophagitis, peptic esophageal strictures, and metaplasia (Barrett’s esophagus). Despite the chronicity of this disorder, prior studies evaluating various therapeutic modalities for severe GERD were short term, with few lasting more than 12 weeks. Moreover, most trials evaluated only one form of therapy, usually a specific antisecretory or prokinetic agent or surgical fundoplication. This study by Spechler et al. represents the first attempt to examine and compare long-term conventional medical and surgical therapy in a large group of patients with complicated GERD. Patients included in this multicenter trial were identified by clinical records, as well as reviews of barium esophagrams and esophagogastroduodenoscopic (EGD) examinations. Inclusion criteria included the presence of peristaltic contractions during esophageal manometry and endoscopic or histological evidence of esophagitis. In addition, gastroesophageal reflux was detected in each patient by the use of 24-hour esophageal pH monitoring. Twohundred forty seven patients (98% men) were randomized by computer to one of three treatment groups: (a) continuous medical therapy, (b) symptomatic therapy, and (c) surgical therapy consisting of a Nissen fundoplication. The three treatment groups did not differ with regard to age, lower esophageal sphincter (LES) pressure, episodes of reflux, the histological grade of esophagitis, or the presence of esophageal ulcers, strictures, and Barrett’s esophagus. Furthermore, the GERD activity index, a standardized system for scoring clinical activity, was nearly identical for each randomized treatment group before the institution of therapy. General antireflux maneuvers were prescribed for all patients and included elevation of the head of the bed, the avoidance of medication known to decrease LES pressure, and the prohibition of smoking, alcohol, bedtime snacks, and foods known to precipitate heartburn in individual persons. In addition, all patients were permitted the use of antacid tablets as needed and esophageal dilation as needed for dysphagia. Patients in group one were given antacid tablets after meals and ranitidine, 150 mg, twice daily. For persistent symptoms, metoclopramide, 10 mg four times daily, was added, and for those patients unresponsive to these medications a sucralfate slurry was included in the regimen. Group two patients were treated symptomatically only in a stepwise fashion, starting with antacid tablets and progressing to ranitidine, metoclopramide, and finally sucralfate as needed to alleviate heart-
November 1992
burn. In the final group of patients, a Nissen fundoplication was performed, after which no antireflux medication was administered. Patients were evaluated every 3 months for symptoms, adverse events, and compliance, and the GERD activity index was calculated. Six weeks after beginning therapy and every year thereafter, patients underwent esophageal manometry, barium esophagram, EGD, and Z&hour pH monitoring studies, and the objective parameters indicated previously were assessed. Follow-up data were available for 176 patients at 1 year and for 106 patients at 2 years. The mean GERD activity index score improved significantly in all three treatment groups: from 108 to 87 in group 1 (continuous medical therapy), from 107 to 88 in group z (symptomatic therapy), and from 109 to 78 in group 3 (surgical group). The histological grade of esophagitis decreased significantly in their respective groups from 2.9 to 2.0, from 2.9 to 2.3, and from 2.9 to 1.4. Improvements in both the mean GERD activity index score and histology were significantly better in the surgically treated group of patients than in either group treated medically. Furthermore, patient satisfaction was significantly greater in the surgical group of patients than in either medical group, and more treatment failures occurred in groups one and two than in patients who underwent Nissen fundoplication. Finally, no operative or perioperative deaths occurred, and the frequency of adverse effects of therapy was similar in all three groups. Based on the results of the trial, the authors conclude that in men with complicated GERD, although medical therapy is effective, operative fundoplication is significantly superior in improving symptoms associated with the disofder and in improving the endoscopic signs of esophagitis. GERD is an extremely common, chronic condition with a wide spectrum of manifestations, of which heartburn is the most common. According to a recent poll (Gallup Organization, 1988), heartburn occurs daily in 14% and at least once monthly in 44% of adult Americans. The majority of these individuals have only mild and sporadic symptoms that are controlled with overthe-counter preparations, such as antacids, and these persons rarely otherwise seek medical attention. Those persons with more severe and persistent symptoms often will obtain the advice of a physician. However, the majority of these patients will be found to have nonerosive GERD on endoscopic evaluation. Only lO%20% of those who seek medical attention will develop serious complications of chronic reflux, which include erosive esophagitis, peptic esophageal strictures, Barrett’s esophagus, and tracheopulmonary aspiration (Arch Intern Med 1991;151:448-454). Effective therapy for GERD is based on a thorough understanding of the pathophysiology and natural history of the disease. The pathophysiological mechanisms involved are primarily motor in nature and include inappropriate relaxations of the LES, inadequate esophageal clearance of refluxed materials, and delayed gastric emptying (Ann Intern Med 1982;97:93-103). The first stage of therapy involves lifestyle modifications and consists of either elevating the head of the bed or the use of a wedge that elevates the patient’s entire thorax, weight loss, avoidance of tight-fitting garments, decreasing the size and composition of meals, and abstinence from known precipitants of gastroesophageal reflux. Such suggestions are often met with resistance by patients who more often than not prefer a prescription that will enable them to enjoy the lifestyle they have chosen to lead.
Comment.
SELECTED SUMMARIES 1697
Despite improvements in our understanding of the disorder and the availability of prokinetic medications that correct motor abnormalities, the use of these drugs as single agents for the treatment of GERD has been largely disappointing. The pathogenesis of GERD does involve disturbances in normal gastroesophageal motility; however, the symptoms and complications of GERD occur as a result of the acidic material being refluxed. Although mean basal gastric acid secretion in patients with GERD is either normal (Gastroenterology 1991;101:1149-1158) or minimally elevated (Gastroenterology 1992;102:2182-2183), the use of drugs that either neutralize gastric acidity or block hydrogen ion generation or secretion has historically comprised the foundation of medical therapy. Antacids and compounds containing alginic acid are very useful for those patients with mild, uncomplicated episodic heartburn. However, owing to their short duration of action, symptom relief may be transient, necessitating the use of repeated doses of these drugs. Furthermore, the relief of nocturnal symptoms is often unsatisfactory, and the use of repeated doses of highpotency antacids may precipitate diarrhea. Histamine HZ-receptor antagonists have become the mainstay of therapy for GERD. However, several unresolved issues remain regarding their optimal use in the disorder, many of which are exemplified in this study by Spechler et al. As indicated previously, GERD is a disorder characterized by a wide spectrum of clinical severity. HZ-antagonists are often not as useful as antacids in patients with mild episodic heartburn owing to their delayed onset of action. In contrast, the HZ-receptor antagonists are very effective in alleviating symptoms in most patients with frequent, recurrent episodes of heartburn who require medication on a daily basis. However, what is the optimal dose of HZ-blockers, and what is the proper dosing interval for these drugs? The answer to these questions relies on the recognition that GERD and duodenal ulcer disease represent different entities, a perception that is unfortunately often disregarded by many physicians and licensing agencies. The latter disorder is generally characterized by exacerbations of disease activity lasting for several weeks, followed by remissions of various duration. Patients with active duodenal ulcer can be treated with HZ-receptor antagonists, which, when given in a single nocturnal dose over a 4-week period, will heal approximately 75%-85% of ulcers. Moreover, maintenance therapy for duodenal ulcer, consisting of nocturnal, lowdose HZ-receptor blockade, is highly effective in preventing ulcer recurrence. In contrast, GERD is a chronic disorder that requires long-term therapy in most individuals. Often, the medical regimen that alleviates symptoms or controls complications is the one that will be required to maintain a patient in remission for weeks, months, or, at times, years. The treatment of GERD should be individualized to the severity of patients’ symptoms and the degree of esophagitis and other complications of acid reflux. Many. if not most, patients with nonerosive GERD who require continuous therapy can be managed with an HZ-blocker, given in two daily doses, as was done in this report by Spechler et al. However, as was also shown in this study, many individuals with complicated GERD do not respond to such a drug regimen but rather require “intensive therapy.” What is the definition of “intensive medical therapy” and what is the role of surgical intervention for patients with GERD? As shown in this study, the results of surgery can be quite gratifying and may often enable patients to significantly improve their quality of life. In addition, owing to the chronic nature of this disorder, antireflux surgery may represent the most cost-effective means of therapy in young patients faced with the prospect of life-longmedical therapy. However, antireflux surgery is generally reserved today for patients who are refractory to medical therapy, who are noncompliant, or who have intolerable complications of GERD, such as continued tracheopulmonary aspiration. Unfortunately, a clear definition of intensive therapy cannot be deduced from the
1698
SELECTED SUMMARIES
GASTROENTEROLOGY Vol. 103, No. 5
present report. Although this was a carefully designed and extensive study, Spechler et al. did not foresee the relatively recent evolution in medical therapy for this chronic disorder. An intensive medical regimen was employed in this study. However, such a regimen consisting of four different drugs has been obviated by the use of either high doses of HZ-receptor antagonists (Gastroenor the substituted benzimidazole ometerology 1990;98:654-661) prazole (N Engl J Med 1991;324:965-975). Despite this one shortcoming, by virtue of its design, the study by Spechler et al. has provided important information regarding the natural history and appropriate therapy of GERD. As stated previously, it represents the first attempt to examine and compare long-term conventional medical and surgical therapy in a large group of patients with GERD. Furthermore, it shows that an intensive medical regimen can be employed to effectively and safely treat the symptoms of GERD and complications associated with long-standing gastroesophageal reflux of acid. Finally, of utmost importance, the study confirms the necessity to individualize medical therapy according to the requirements of each individual patient. M. M. WOLFE, M.D.
CAN ESOPHAGUS BE BLAMED NONCARDIAC CHEST PAIN?
FOR
Hick DG, Morrison
jFJ3, Casey IF, et al. (Cardiac Research Unit, Killingbeck Hospital, Leeds, England; and the Department of Physiology, University of Leeds, Leeds, England). Oesophageal motility, luminal pH, and electrocardiographic-ST segment analysis during spontaneous episodes of angina like chest pain. Gut 1992;33:79-86.
The esophagus, as the source of noncardiac chest pain, has been extensively studied during the last 10 years. After careful exclusion of cardiac etiology, a significant number of patients are found to have esophageal contraction abnormalities. These esophageal contraction abnormalities are thought to be the cause of chest pain. However, there is a lack of direct correlation between abnormal esophageal contractions and chest pain. The study in review by Hick et al. is another attempt to define the cause and effect relationship between chest pain and the esophagus. These investigators studied 46 patients with anginalike chest pain of >6 months in whom cardiac evaluation, including coronary angiography, was normal. Ambulatory esophageal motility, pH monitoring, and EKG recordings were obtained for 24 hours in the patient’s home environment, and patients were encouraged to pursue those activities known to provoke symptoms.
The pressures were recorded at 5,10, and 15 cm above the upper border of the lower esophageal sphincter (LES) using a solid state transducer system. The esophageal pH was recorded at 7.5 ems above the LES. A thirty-minute period before and a 30-minute period after the occurrence of chest pain was used as a control and compared with the data during pain periods. All of the manometric, pH, and EKG data were analyzed using a software and computer. A standard esophageal motility using infusion manometry and station pullthrough technique was performed before ambulatory recordings in these patients. These manometric data were compared with the control data published in the literature.
The results of the standard motility study show the contraction amplitudes to be somewhat lower in the patient population than controls and the contraction duration to be significantly higher in the patients but only in the distal esophagus. The LES pressure was significantly higher in the patients. There was no distinct contraction abnormality or acid reflux seen during ambulatory studies during 59 pain events in 35 patients. Even though there was no direct temporal correlation between the occurrence of chest pain and the acid reflux events, 70% of the patients showed a pathological degree of reflux on .&hour pH score. Gastroesophageal reflux occurred mostly in the supine rather than upright position. Two episodes of chest pain correlated with EKG changes suggestive of ischemia. Comments. Seven studies of ambulatory esophageal motility and pH recordings have been reported in the recent literature. The intent of these studies was to establish a cause and effect relationship between chest pain and pathological esophageal events such as contraction abnormality and acid reflux. The contraction abnormality was thought to be the cause of chest pain in o%-43% of the instances and acid reflux the cause of chest pain during O%-30% of the events among various studies. Table 1 shows various aspects such as numbers and patient population studied, total number of pain episodes recorded, Bernstein test, 24 hour pH scores and the temporal relationship between chest pain and pathological esophageal event. Studies 2 and 6 in Table 1 reported that in about 30% of the patients either an abnormal esophageal contraction or acid reflux can be documented at the time of chest pain. However, a clear definition of abnormal contraction was not provided in these studies. Studies 5 and 7 (same investigator group) provide the most optimistic figures in terms of identification of a pathological event at the moment of chest pain. The various criteria used by various authors to define an abnormal esophageal contraction and acid reflux are shown in Table 2. Based on these criteria, it is not surprising that different investigators have come up with different numbers. Is one criteria better than the other and what should be the best criteria? It appears that the most rigorous criteria for abnormal contraction and acid reflux was used by Peters et al. (Gastroenterology 1988;94:878886) and they found only a modest temporal relationship between pathological esophageal event and chest pain. Symptom index, defined as the frequency of pain events associated with the pathological events, of greater than 75% has been accepted to establish the cause and effect relationship. A positive symptom index for reflux and contraction abnormality has been reported in up to 43% and 33% of patients respectively. However, if one looks at the frequency of pathological events (abnormal motility and acid reflux) causing chest pain, one finds no relationship. In the absence of a clear temporal association between chest pain and pathological esophageal event, one wonders if the esophagus can really cause chest pain. Provocation of chest pain during Bernstein test and esophageal distension clearly establishes that the esophagus is capable of causing chest pain. Twenty to 70% of patients with chest pain have pathological 24-hour acid reflux scores. It is possible that in some patients acid sensitive receptors in the esophagus interpret the heartburn sensation as chest pain sensation. Clearly these patients respond to antireflux therapy. However, a subgroup of patients, not responsive to antireflux therapy may have an abnormal motility parameter such as longitudinal muscle contraction of the esophagus that cannot be measured by intraluminal pressure measurement technique. This is based on the observation that afferent activity from the tension receptors correlates with the longitudinal rather than circular muscle contraction.
