Walter J. Hogan

Mechanisms of Gastroesophageal Reflux in Patients with Reflux Esophagitis

We evaluated the mechanisms of gastroesophageal reflux in 10 patients with reflux esophagitis and compared the results with findings from 10 controls. The patients had more episodes of reflux (35 +/- 15 in 12 hours, as compared with 9 +/- 8 in the controls) and a lower pressure of the lower esophageal sphincter (13 +/- 8 mm Hg as compared with 29 +/- 9 in the controls) (P less than 0.001). Reflux occurred by three different mechanisms: transient complete relaxation of the lower esophageal sphincter, a transient increase in intra-abdominal pressure, or spontaneous free reflux associated with a low resting pressure of the lower esophageal sphincter. In controls 94 per cent of reflux episodes were caused by transient sphincter sphincter relaxation. In the patients 65 per cent of episodes of reflux accompanied transient sphincter relaxation, 17 per cent accompanied a transient increase in intra-abdominal pressure, and 18 per cent occurred as spontaneous free reflux. The predominant reflux mechanism in individual patients varied: some had normal resting sphincter pressure and reflux that occurred primarily during transient sphincter relaxation, whereas others with low resting sphincter pressures had spontaneous free reflux or reflux that occurred during an increase in intra-abdominal pressure.

Mechanism of gastroesophageal reflux in recumbent asymptomatic human subjects.

We investigated the mechanism of gastroesophageal reflux (GER) in 10 health volunteer subjects. Continuous recordings of intraluminal esophageal pH and pressure were obtained on two consecutive nights from 6:00 p.m. to 6:30 a.m. in each subject. During each study, the subject remained recumbent, except to eat a standardized meal after 1 h of basal recording. A manometric assembly with seven recording lumens monitored: (a) lower esophageal sphincter (LES) pressure via a sleeve device 6.5 cm in length, (b) esophageal-body motor activity, (c) swallowing activity in the pharynx, and (d) gastric pressure. An electrode 5 cm above the LES recorded esophageal pH. Sleep was monitored by electroencephalogram. All subjects showed wide variations of basal LES pressure. GER was not related to low steady-state basal LES pressure, but rather occurred during transient 5-30 s episodes of inappropriate complete LES relaxation. The inappropriate LES relaxations were usually either spontaneous or immediately followed appropriate sphincter relaxation induced by swallowing. The majority of GER episodes occurred within the first 3 h after eating. During the night LES relaxation and GER occurred only during transient arousals from sleep or when the subjects were fully awake, but not during stable sleep. After GER the esophagus was generally cleared of refluxed acid by primary peristalsis and less frequently by secondary peristalsis. Nonperistaltic contractions were less effective than peristalsis for clearing acid from the esophagus. We conclude that in asymptomatic recumbent subjects GER is related to transient inappropriate LES relaxations rather than to low steady-state basal LES pressure and also, that primary perstalsis is the major mechanism that clears the esophagus of refluxed material.

Esophageal Peristaltic Dysfunction in Peptic Esophagitis

Esophageal exposure to acid is a major determinant in the pathogenesis of reflux esophagitis. In this study, we analyzed the esophageal peristaltic function of 177 patients and asymptomatic volunteers for abnormalities that could lead to prolonged esophageal acid clearance. The subjects were divided into five groups: normal volunteers, patient controls, patients with noninflammatory gastroesophageal reflux disease, patients with mild esophagitis, and ones with severe esophagitis. Manometric data were analyzed for the occurrence of failed primary peristalsis, for the occurrence of feeble peristalsis in the distal esophagus, and for hypotensive lower esophageal sphincter pressure. From an analysis of the data on control patients, peristaltic dysfunction was defined as the occurrence of either failed primary peristalsis or hypotensive peristalsis in the distal esophagus for over half of the test swallows. Peristaltic dysfunction was increasingly prevalent with increasing severity of peptic esophagitis, occurring in 25% of patients with mild esophagitis and 48% of patients with severe esophagitis. A correlation did not exist between the occurrence of peristaltic dysfunction and hypotensive lower esophageal sphincter pressure (less than or equal to 10 mmHg). We conclude that peristaltic dysfunction occurs in a substantial minority of patients with peptic esophagitis and could contribute to increased esophageal exposure to refluxed acid material.

Effect of peristaltic dysfunction on esophageal volume clearance

Prolonged esophageal acid clearance, found in some patients with esophagitis, can be attributed in part to the peristaltic dysfunction observed in this population. In this study, we undertook to define the effect of commonly observed peristaltic dysfunction on volume clearance by obtaining concurrent videofluoroscopic and manometric recordings in patients with nonobstructive dysphagia or heartburn. Excellent correlation existed between the findings from the two studies. A single normal peristaltic wave resulted in 100% clearance of a barium bolus from the esophagus. At each recording site, luminal closure, as demonstrated by videofluoroscopy, coincided with the upstroke of the peristaltic pressure complex. Absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance from the involved segment. Regional hypotensive peristalsis was associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction. The regional peristaltic amplitude required to prevent retrograde escape of barium was greater in the distal compared with the proximal esophagus. The mean peristaltic amplitude associated with instances of retrograde escape was 25 mmHg in the distal esophagus compared with 12 mmHg in the proximal esophageal segments. Thus, the peristaltic dysfunction commonly seen in patients with esophagitis (failed and hypotensive peristalsis) likely leads to impaired volume clearance.

The Efficacy of Endoscopic Sphincterotomy after Cholecystectomy in Patients with Sphincter-of-Oddi Dysfunction

Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction.

Effect of esophageal emptying and saliva on clearance of acid from the esophagus

We studied clearance of acid from the esophagus and esophageal emptying in normal subjects. A 15-ml bolus of 0.1 N hydrochloric acid (pH 1.2) radiolabeled with [99mTc]sulfur colloid was injected into the esophagus, and the subject swallowed every 30 seconds. Concurrent manometry and radionuclide imaging showed nearly complete emptying of acid from the esophagus by an immediate secondary peristaltic sequence, although esophageal pH did not rise until the first swallow 30 seconds later. Esophageal pH then returned to normal by a series of step increases, each associated with a swallow-induced peristaltic sequence. Saliva stimulation by an oral lozenge shortened the time required for acid clearance, whereas aspiration of saliva from the mouth abolished acid clearance. Saliva stimulation or aspiration did not affect the virtually complete emptying of acid volume by the initial peristaltic sequence. We conclude that esophageal acid clearance normally occurs as a two-step process: (1) Virtually all acid volume is emptied from the esophagus by one or two peristaltic sequences, leaving a minimal residual amount that sustains a low pH, and (2) residual acid is neutralized by swallowed saliva.

Pathogenesis of Reflux Esophagitis

During the past decade considerable new information has accrued about reflux esphagitis and the physiology of esophageal motor function. Although numerous reports review the clinical, diagnostic, and therapeutic aspects of reflux esophagitis (1-6), few reports (7) focus primarily on the pathophysiology of esophagitis production. Our purpose here is to: (a) review critically recent findings relevant to the pathophysiology of reflux esophagitis, (b) analyze factors that may contribute to the production of reflux esophagitis, and (c) identify appropriate questions that merit further investigation. Throughout the report we will endeavor to alert the reader when the manuscript reflects our own opinion, speculation, or scientific bias as opposed to established observations. For this report the term reflux esophagitis is defined as esophageal inflammation caused by refluxed material. On endoscopy reflux esophagitis may cause visible discoloration, friability, ulceration, exudate, or luminal narrowing. In active reflux esophagitis, histologic sections demonstrate an acute polymorphonuclear or a mixed polymorphonuclear and round cell infiltrate, generally accompanied by epithelial erosion or ulceration. These gross or histologic findings are necessary for a specific diagnosis of reflux esophagitis. In some patients with clinical complaints suggesting GE reflux, the esophagus appears normal at endoscopy and no evidence of inflammation is present on biopsy. Biopsies

Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis

BACKGROUND Chronic pancreatitis in its early stages may defy diagnosis despite existing diagnostic modalities. Endoscopic retrograde pancreatography (ERCP), secretin test, and conventional ultrasound are insensitive in detecting the early stages of chronic pancreatitis. The aim of this study was to determine whether endoscopic ultrasonography (EUS) high-resolution imaging allows for the detection of chronic pancreatitis as compared with clinical history, ERCP, and secretin test. METHODS Eighty consecutive patients with recurrent pancreatitis underwent ERCP, EUS, and secretin test. EUS evaluated parenchymal changes: echogenic foci (calcification), prominent interlobular septae (fibrosis), small cystic cavities (edema), lobulated outer gland margin (fibrosis/atrophy), and heterogeneous parenchyma; and ductal changes: dilation, irregularity, echogenic wall (fibrosis), side-branch ectasia, and echogenic foci (stones). EUS criteria for chronic pancreatitis included mild (1 to 2 features), moderate (3 to 5 features), and severe (more than 5 features). RESULTS Abnormal studies were EUS = 63, ERCP = 36, and secretin test = 25. Secretin test had 100% agreement with normal and severe chronic pancreatitis by EUS criteria, but agreement was poor for mild (13%) and moderate (50%) disease. Alternatively, the agreement between ERCP- and EUS-specific criteria was excellent for normal (100%), moderate (92%), and severe (100%) chronic pancreatitis and poor for mild (17%) disease. When the 2-test modality (ERCP and secretin test) was compared with EUS alone, no enhancement in agreement was seen. CONCLUSION Using the above criteria EUS may assist in the diagnosis of chronic pancreatitis not established by ERCP or secretin test. Excellent agreement can be expected between EUS and ERCP in the diagnosis of chronic pancreatitis with the exception of mild changes noted on EUS (kappa statistics = 0.82: 95% CI [0.70, 0.95]). Long-term follow-up of the patients with mild EUS changes will determine the validity of EUS in diagnosing the early stages of chronic pancreatitis.

Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features

BACKGROUND Eosinophilic esophagitis is an inflammatory condition in which there is dense eosinophilic infiltration of the surface lining of the esophagus. Reports of eosinophilic esophagitis pertain almost exclusively to pediatric populations. However, eosinophilic esophagitis is emerging as a clinical affliction of adults. This report describes the clinical and endoscopic findings of eosinophilic esophagitis in the largest cohort of adult patients reported to date. METHODS Twenty-nine patients (21 men, 8 women; mean age 35 years) with documented eosinophilic esophagitis (>/=15 eosinophils per high-power field in biopsy specimens) and a significant history of chronic dysphagia for solid food (24 patients) were evaluated clinically and endoscopically during a 3-year period (1999-2002). Fourteen patients (48%) had a history of asthma, environmental allergy, or atopy. In a subset of 15 patients, the diagnostic accuracy of endoscopy was compared with that of barium contrast esophagography. RESULTS Twenty-seven patients (93%) had abnormal endoscopic findings; 25 (86%) had unique esophageal structural changes, associated with a preserved mucosal surface, that were highly atypical for acid reflux injury. Structural alterations seen in adult patients with eosinophilic esophagitis may occur in combination or as a primary characteristic, e.g., uniform small-caliber esophagus, single or multiple corrugations (rings), proximal esophageal stenosis, or 1 to 2 mm whitish vesicles scattered over the mucosal surface. Barium contrast radiography combined with swallow of a barium-coated marshmallow identified 10 (67%) of the primary features observed endoscopically in 15 patients. However, radiography failed to detect other features noted at endoscopy (e.g., only 3/6 patients with proximal stenosis, 5/9 patients with concentric rings and none of 4 patients with small caliber esophagus). Eight of the 29 patients (20%) had a history of chronic heartburn. Twelve patients had been treated with a proton pump inhibitor and only 3 reported some improvement in the severity of dysphagia. CONCLUSIONS Relatively young age, a history of chronic dysphagia for solid food, and endoscopic detection of unique structural alterations atypical for GERD in an adult patient should prompt a suspicion of EE and subsequent biopsy confirmation. Acid reflux appears to have a secondary role in eosinophilic esophagitis. In an uncontrolled comparison, endoscopy was superior to barium contrast radiography for the diagnosis of eosinophilic esophagitis. The incidence of eosinophilic esophagitis in adults appears to be increasing.

Esophagopharyngeal Distribution of Refluxed Gastric Acid in Patients with Reflux Laryngitis.

BACKGROUND & AIMS A variety of otolaryngological abnormalities have been attributed to the contact of gastroesophageal refluxate with respective structures of the aerodigestive tract. The aim of this study was to determine and compare the pharyngoesophageal distribution of gastric acid refluxate between patients with proven laryngitis attributed clinically to gastroesophageal reflux and three control groups. METHODS An ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring technique was used to measure reflux parameters in the pharynx, proximal esophagus, and distal esophagus. RESULTS Between-group comparison showed no significant difference in the reflux parameters in the distal esophagus between the studied groups. A significantly higher percentage of distal reflux episodes reached the proximal esophagus in the laryngitis group than in the control groups (P < 0.01), and the number of pharyngeal reflux episodes and time of acid exposure were significantly higher in the laryngitis group than in the control groups (P < 0.001). CONCLUSIONS Compared with normal controls and patients with gastroesophageal reflux disease, pharyngeal reflux of gastric acid is significantly more prevalent and the ratio of proximal to distal esophageal acid reflux episodes is significantly increased in patients with posterior laryngitis. Simultaneous three-site ambulatory pharyngoesophageal pH monitoring may provide supporting evidence when the diagnosis of reflux-induced aerodigestive tract lesions is considered.