Charles E. Pope

Histological Consequences of Gastroesophageal Reflux in Man

Esophageal suction biopsy specimens were obtained from 33 subjects with, and 21 without, subjective and objective evidence of gastroesophageal reflux. From these specimens the appearance of the normal esophageal mucosa was established and histological features of the mucosa in presence of gastroesophageal reflux were determined. These features are: (a) basal cell hyperplasia of the squamous epithelium, and (b) location of the papillae close to the epithelial surface. A good correlation is shown between these features and symptoms, acid reflux studies, and esophagoscopy. It is concluded that these features are the histological consequences of gastroesophageal reflux.

The gastroesophageal flap valve: in vitro and in vivo observations

BACKGROUND This study was performed to confirm the presence and significance of a gastroesophageal flap valve. METHODS The pressure gradient needed to induce reflux across the gastroesophageal junction and the level of a high-pressure zone were determined in 13 cadavers. On inspection in the cadavers, a mucosal flap valve at the entrance of the esophagus into the stomach was seen through a gastrostomy. This valve was deficient or absent in cadavers with a hiatal hernia. The valve was inspected in controls and in patients with reflux with a retroflexed endoscope. RESULTS In cadavers with no hiatal hernia, a gradient across the gastroesophageal junction was present in nearly all cadavers. The gradient could be increased by surgically accentuating the valve without a concomitant rise in pressure in the high-pressure zone. Reduction of the hiatal hernia in the cadaver and anchoring of the gastroesophageal junction to the normal attachment to the preaortic fascia restored the valve and the gradient as seen through a gastrostomy. Control subjects had a prominent fold of tissue that extended 3 to 4 cm along the lesser curve of the stomach and tightly grasped the shaft of the endoscope. This was diminished or absent in reflux patients. Inspection of the valve in control subjects and subjects with reflux allowed for a grading system with Grades I through IV. This grading system was applied to a cohort of patients with and without reflux. The appearance of the flap valve was a better predictor of the presence or absence of reflux than was lower esophageal sphincter pressure. Endoscopic viewing of the valve during surgery can confirm that a competent valve has been reconstructed. CONCLUSIONS Grading of the gastroesophageal valve is simple, reproducible, and offers useful information in the evaluation of patients with suspected reflux undergoing endoscopy.

Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus.

We analyzed the clinical, radiographic, esophageal manometric, and pathologic features of 26 women with severe, idiopathic constipation. Twenty-four patients were between 19 and 39 yr of age. Stool frequency was once every 5-28 days. On barium enema examination, 9 of 24 patients had colons of increased length and 4 of these 9 patients had colons of increased width (greater than 10 cm). Radionuclide solid-meal gastric-emptying studies were normal in 23 patients tested. Esophageal manometry demonstrated high-amplitude waves in 10 of 22 patients and long-duration waves in 3 of these 10 patients. Rectal biopsy specimens showed normal submucosal neurons in all patients and melanosis coli in 6. Twelve patients underwent subtotal colectomies for constipation. Conventional light microscopy using hematoxylin and eosin serial sections showed (a) melanosis coli in 4 patients; (b) normal smooth muscle in 11; (c) thinning of the circular muscle in 1; and (d) no apparent abnormalities of the myenteric plexus in any. In contrast, silver stains of the myenteric plexus showed (a) quantitatively reduced numbers of argyrophilic neurons in 10 patients; (b) morphologically abnormal argyrophilic neurons in 11; (c) decreased numbers of axons in 11; and (d) increased numbers of variably sized nuclei within ganglia in all 12. A coded analysis of the silver stains of colons from 8 patients with constipation and 19 control cases demonstrated that the pathologic abnormalities of severe idiopathic constipation could be differentiated from controls. Thus, severe idiopathic constipation is associated with a pathologically identifiable abnormality of the myenteric plexus. This abnormality appears different from anything previously described in intestinal pseudoobstruction.

A Dynamic Test of Sphincter Strength: Its Application to the Lower Esophageal Sphincter

Summary Measurement of sphincter force of closure has been achieved by utilizing intraluminal infusion of microliter quantities of fluid. This infusion causes an elevation in recorded pressure (yield pressure) when the catheter tip is within a sphincter. The yield pressure agrees exactly with force of closure in a model sphincter and predicts model sphincter strength more exactly than do other methods currently employed for sphincter measurement. The infusion system described has been used to study 40 subjects whose degree of lower esophageal sphincter competence has been defined on either clinical grounds (symptom of heartburn) or by objective measurement (Tuttle test). Subjects with competent sphincters had significantly higher yield pressures than did those subjects without competent sphincters. The overlap of yield pressures was least when the presence or absence of competence was defined by the Tuttle test. No significant difference between competent and incompetent sphincters was found when resting lower esophageal sphincter pressures were measured. It is concluded that infusion of microliter quantities of fluid into the lumen of a closed sphincter allows more accurate prediction of sphincter force of closure than does static measurement of intrasphincteric pressure.

Cimetidine in the treatment of symptomatic gastroesophageal reflux: a double blind controlled trial.

The effectiveness of cimetidine for symptomatic relief in patients with chronic gastroesophageal reflux was studied in a multicenter, double blind clinical trial. Patients were entered into the study for a total of 8 weeks, receiving either cimetidine, 300 mg four times daily, or identical placebo tablets. Throughout the trial, frequent assessments were made of symptom severity and frequency, combined with careful measurement of antacid use. Esophagoscopy, esophageal acid sensitivity, and lower esophageal pressures were performed before and at the completion of the treatment period. Significant (P less than 0.05) decreases in symptom frequency and severity were noted throughout the study in the cimetidine-treated patients, as compared with the placebo group. This subjective improvement was corroborated by a concomitant decrease in antacid use, which was significantly (P less than 0.05) reduced in the cimetidine-treated group. In addition, significant improvement in esophageal acid sensitivity resulted from cimetidine therapy. No objective improvement in esophageal endoscopic appearance or sphincter pressures was noted. The results of this double blind trial indicate that cimetidine is more effective than the placebo for the relief of symptoms of gastroesophageal reflux.

Distribution of the Histological Changes of Gastroesophageal Reflux in the Distal Esophagus of Man

To discover the distribution of histological changes associated with esophageal reflux, multiple biopsies with the Quinton hydraulic tube were obtained from the distal 10-cm of the esophagus in 34 subjects with demonstrated reflux and in 10 control subjects without reflux. The safety and adequacy of hydraulic biopsy was demonstrated. It was found that the reflux lesions were distributed randomly over the distal 8 cm of esophagus. This finding suggests that precise manometric localization of biopsy site is not necessary and that multiple biopsies are helpful.

Acid-Reflux Disorders

In recent years, the concept of acid-reflux disorders has been broadened to include not only the effects of gastroesophageal reflux on the esophageal mucosa but also the role of acid reflux in lary...

Esophageal reflux—an unrecognized cause of recurrent obstructive bronchitis in children

Forty-three children with recurrent obstructive bronchitis but without prominent gastrointestinal symptoms were studied for esophageal reflux roentgenographically and by manometry. Roentgenographic evidence for reflux was shown in 26; these patients had a mean lower esophageal sphincter pressure of 6.3 mm Hg as compared to a mean LES pressure of 21.9 mm Hg in normal control infants. The remaining 17 patients had a mean LES pressure of 10.0 mm Hg, also significantly lower than that of control subjects. Fifteen of 20 patients with recurrent obstructive bronchitis noted alleviation of their pulmonary symptoms after medical treatment of their reflux. Sequential studies of another group with radiologically demonstrated reflux showed increases in sphincter pressures and disappearance of radiologically observed reflux in one third of the patients. It is suggested that esophageal reflux should be sought in patients with recurrent bronchitis: if found, antireflux therapy might be expected to improve the pulmonary symptomatology.

The quality of life following antireflux surgery

To improve the quality of life after antireflux surgery, the patient should notice improvement or disappearance of the symptoms leading to the surgery and should not acquire any new symptoms resulting from antireflux surgery. Published accounts of antireflux surgery results vary widely. Part of this variation may be due to nonstandard methods of evaluating symptoms. A system of symptom evaluation is proposed which takes into account the intensity and frequency of symptoms. It is hoped that this system will allow surgeons to refine and improve their techniques and results.

Laryngoscopy and pharyngeal pH are complementary in the diagnosis of gastroesophageal-laryngeal reflux.

Pharyngeal pH monitoring and laryngoscopy are routinely used to diagnose gastroesophageal-laryngeal reflux as a cause of respiratory symptoms. Although their use seems intuitive, their ultimate diagnostic value is yet to be defined. We studied 10 asymptomatic (control) subjects and 76 patients with respiratory symptoms. Both patients and control subjects were given a symptom questionnaire. Each underwent direct laryngoscopy using the reflux finding score (RFS) to grade laryngeal injury, esophageal manometry, and 24-hour esophagopharyngeal pH monitoring. The patients were then classified as RFS+, if the score was greater than 7, and pharyngeal reflux (PR)+, if they had more than one episode of PR detected during pH monitoring. The most common symptoms reported by patients were hoarseness (87%), cough (53%), and heartburn (50%). Control subjects had a significantly lower RFS (2.1 vs. 9.6, P < 0.01) and fewer episodes of PR (0.2 vs. 3.4, P < 0.01), than patients. None of the control subjects had more than one episode of PR during a 24-hour period. Fifty patients (66%) were RFS+ and 26 (34%) were RFS—. Thirty-two patients (42%) were PR+ and 44 (58%) were PR-. Fifteen patients had a normal RFS and no PR (group I = RFS—/PR—). Forty patients had discordance between the laryngoscopic findings and the pH monitoring (group II = RFS—/PR + or RFS+/PR—). Twenty-one patients had both an abnormal RFS and PR (group III = RFS+/PR+). Patients in group III had significantly higher heartburn scores and distal esophageal acid exposure. Eighty-three percent of patients in group III but only 44% in group I improved their respiratory symptoms as a result of antireflux therapy. An abnormal PR or RFS differentiates patients with laryngeal symptoms from control subjects. Agreement between PR and RFS helps establish or refute the diagnosis of gastroesophageal reflux as a cause of laryngeal symptoms. Patients who are RFS+ and PR—may have laryngeal injury from another source, whereas patients who are RFS— and PR+ may not have acid entering the larynx, despite the presence of PR. Patients who are RFS+ and PR+ have more severe gastroesophageal reflux disease and their reflux causes laryngeal damage. Laryngoscopy and pharyngeal pH monitoring should be considered complementary studies in establishing the diagnosis of laryngeal injury induced by gastroesophageal reflux.