Lower Esophageal Sphincter Dysfunction Research Articles

Effect of Melatonin in Functional Heart Burn-A Randomized Placebo-Controlled Clinical Trial

Purpose: Functional heart burn is a challenging clinical entity. Rome III criteria confirmed the clinical state. The subjects of collective, nonerosive reflux disease (NERD) with negative diagnostic studies, including histopathology and lower esophageal sphincter dysfunction, fall into the category of Functional Heart Burn (FHB) after a proton pump inhibition (PPI) challenge test. Therapeutic modalities are not yet established. Melatonin, a natural neurohormone related to serotonin, inhibits gastric acid secretion, alters nitric oxide function at gastroesophageal junction, and helps heal esophageal erosions. This study evaluates the possible role of melatonin in FHB.Methods: Sixty patients (n=60), ages 21-42 years (mean of 33), with Rome III proven FHB, were randomized into three groups. All patients underwent initial PPI challenge for 4 weeks, followed by panendoscopy with biopsies of antrum, body, distal and proximal esophagus. H. pylori, eosinophilic esophagitis (EoE) and mast cells were evaluated. All patients underwent pH monitoring (RESTEC pH monitoring). Group A (n=20) placebo at bedtime, Group B (n=20) Nortryptaline 25 mg orally at bed time, and Group C (n=20) over-the-counter(OTC)melatonin 6 mg at bed time for 3 months. All groups received omperazole 20 mg before breakfast and also underwent lifestyle modification. Pre- and post GERD-HQRL scores were analyzed. Exclusion: active ulcers, EOE, achalasia, esophageal stricture, infections of esophagus, scleroderma, H. pylori gastritis, and drugs affecting motility. Results: Patients in Melatonin group had a significantly higher percentage of relief (15/20=75%; Pearson's Chi-square=12.2, p=0.002) in heart burn score than those in Nortryptaline (4/20=20%) and Placebo (9/20=45%) groups. Melatonin group also had relatively better quality of life, less day time somnolence, and better tolerability compared to the other two groups. Side Effects: Melatonin- 5(25%)distension, 4(20%) diarrhea, and 4(20%) day time somnolence; Nortryptiline- 7(35%) constipation, 9(45%) somnolence, 11(55%) dry mouth, and 2(10%) dizziness; Placebo- 5(25%) constipation, 11(55%) daytime somnolence, and 6(30%) abdominal distension. Conclusion: OTC Melatonin improves functional heart burn and GERDHQRL score, is generally well tolerated, and offers a significant cost benefit. A larger trial is needed to validate.

Lower oesophageal sphincter dysfunction is part of the functional abnormality in epiphrenic diverticulum

The pathophysiology and management of epiphrenic diverticula remain controversial. This study investigated the underlying functional abnormalities and long-term results of surgical treatment. Patients with symptoms and epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV fundoplication were reviewed retrospectively. They were assessed before and after surgery by radiology, functional testing and endoscopy, and compared with a group of 40 normal volunteers. The study included 23 consecutive symptomatic patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower oesophageal sphincter (LOS) incoordination was considered the most constant functional abnormality (P < 0.001). After operation oesophageal diameter increased, contraction pressures decreased and peristalsis was reduced. LOS resting and gradient pressures decreased (P = 0.001). Despite unchanged acid exposure values, endoscopy revealed increased mucosal damage after operation (P = 0.003). New columnar-lined metaplasia was documented in eight patients (P = 0.013). Symptoms had decreased after a median of 61 months (P = 0.001). Epiphrenic diverticulum was associated with spastic dysfunction and LOS abnormalities. A long myotomy including the LOS relieved functional obstruction and symptoms, but partial fundoplication did not prevent reflux damage.

Protective effects of Helicobacter pylori against gastroesophageal reflux disease may be due to a neuroimmunological anti‐inflammatory mechanism

There is some evidence that Helicobacter pylori infection has a protective effect against gastroesophageal reflux disease (GORD) and its complications such as Barrett's oesophagus and oesophageal adenocarcinoma. In this paper, we propose that a neuroimmunological mechanism is responsible for the protective effect of H. pylori on GORD. H. pylori infection of the gastric mucosa induces a T helper1-like immune response and production of pro-inflammatory cytokines. These cytokines can inhibit local sympathetic tone, whereas they increase systemic sympathetic tone. Increased sympathetic tone can induce an anti-inflammatory milieu, which in turn can inhibit inflammation in the oesophagus and lower oesophageal sphincter (LOS). Furthermore, H. pylori infection may stimulate the cholinergic anti-inflammatory pathway. It has been suggested that reflux-induced oesophageal inflammation plays an important role in the pathogenesis of reflux oesophagitis. Reduction of oesophageal inflammation by increased systemic sympathetic tone and vagal activity may lead to a decrease in reflux-induced oesophageal injury and LOS dysfunction in GORD.

Endoscopic, bioptic, and manometric findings in eosinophilic esophagitis before and after steroid therapy: a case series

Eosinophilic esophagitis can be associated with a wide range of endoscopic patterns. The aim of the present case series report is to describe and classify endoscopic appearances before and after corticoid therapy in relation to histopathology and manometry. In 30 patients (m : f, 27 : 3; mean age 36.2 years) with eosinophilic esophagitis, endoscopic findings were prospectively classified according to luminal diameter and mucosal pattern. Manometric and bioptic histopathologic findings were also recorded. Endoscopy was repeated following a 3-month course of steroid therapy. In total, 20 % of patients showed a concentric esophageal stricture, and in 57 % simultaneous contraction rings were visible. Mucosal alterations consisted of granular mucosa (20 %), longitudinal furrows (33 %) and transversal undulations (3 %). Lower esophageal sphincter dysfunction and distal esophageal dysfunctional manometry were seen in 73 % and 57 % of cases, respectively. Following steroids, the esophagus showed a normal caliber in 97 % of patients, and 63 % of patients had normal mucosa. The most frequent findings were narrowing of the esophageal lumen, which returned to normal following steroid treatment to a larger extent than mucosal alterations.

Whistler Summary: “The Slow Rate of Rapid Progress”

Whistler Summary: “The Slow Rate of Rapid Progress”

Transient failure of opening of the lower oesophageal sphincter on upright oesophagrams: radiographic and clinical findings

The purpose of our study was to determine the frequency, radiographic features, and clinical importance of transient failure of opening of the lower oesophageal sphincter (LOS) on upright double-contrast views of the oesophagus. A computerized search of radiology records identified 16 patients who had transient failure of opening of the LOS on upright views from biphasic oesophagrams or upper gastrointestinal tract examinations using high-density barium but normal opening of the LOS on prone views using low-density barium. The radiographic findings were reviewed and correlated with the clinical and manometric findings. In all cases, barium studies revealed tapered, beaklike narrowing of the distal oesophagus on upright double-contrast views, with a normal-appearing distal oesophagus, normal opening of the LOS, and intact peristalsis on prone single-contrast views. Only seven patients (44%) had dysphagia. Five of these patients had clinical follow-up, and the dysphagia improved or resolved without specific treatment for LOS dysfunction in four. The remaining patient had persistent dysphagia, but this individual had polymyositis as the likely cause for his dysphagia. Manometry revealed incomplete relaxation of the LOS in two patients and normal relaxation in one. Our experience suggests that failure of opening of the LOS may be observed as a transient finding of little clinical importance on upright double-contrast views of the oesophagus using high-density barium, with normal opening of the LOS on prone single-contrast views using low-density barium. It is important to be aware of this finding, so that it is not mistaken for achalasia or other abnormalities of the distal oesophagus.

Review article: the pathophysiology of gastro‐oesophageal reflux disease − oesophageal manifestations

The pathogenesis of gastro-oesophageal reflux disease (GERD) is multifactorial, involving transient lower oesophageal sphincter relaxations (TLESRs) as well as other lower oesophageal sphincter (LES) pressure abnormalities. GERD is associated with a decrease in LES pressure, which can be provoked by factors such as foods (fat, chocolate, etc.), alcohol, smoking and medications. These factors have also been shown to increase TLESRs. As a result, reflux of acid, bile, pepsin and pancreatic enzymes occurs, leading to oesophageal mucosal injury, which can potentially progress to oesophageal adenocarcinoma in a minority of patients with Barrett's metaplasia. In addition, duodenogastric contents can also contribute to oesophageal injury. Other factors contributing to the pathophysiology of GERD include hiatal hernia, poor oesophageal clearance, delayed gastric emptying and impaired mucosal defensive factors. Hiatal hernia has a permissive role in the pathogenesis of reflux oesophagitis by promoting LES dysfunction. Delayed gastric emptying, resulting in gastric distension, can significantly increase the rate of TLESRs, contributing to postprandial GER. The mucosal defensive factors have an important role in GERD. When excessive acid causes a breakdown in oesophageal epithelial defenses, epithelial resistance may be reduced. Nocturnal GERD is associated with prolonged acid exposure and proximal extent of acid contact, which elevates the risk for oesophageal damage and GERD-related complications. In sum, GERD is a complex problem caused by many factors that are exacerbated when the patient is in the supine position.

Relationship between diffuse esophageal spasm and lower esophageal sphincter dysfunction on barium studies and manometry in 14 patients.

We sought to reassess the function and clinical characteristics of the lower esophageal sphincter in a series of patients with radiographically defined diffuse esophageal spasm. In reviewing records in the radiology database at our hospital, we identified 14 patients with diffuse esophageal spasm confirmed on barium studies who also underwent esophageal manometry. The radiographic findings were reviewed and correlated with the manometric findings. Medical records were also reviewed to determine the clinical presentation, treatment, and patient course. All 14 patients were symptomatic, presenting with dysphagia, chest pain, or both. All the barium studies revealed intermittently absent or weakened peristalsis, with nonperistaltic contractions that were moderate in six patients (43%) and marked in eight patients (57%) (contractions nearly obliterating the lumen in six and completely obliterating the lumen in two). Nine patients (64%) had impaired opening of the lower esophageal sphincter, manifested by beaklike narrowing of the distal esophagus, and five (36%) had normal opening of the lower esophageal sphincter. Manometry revealed abnormal peristalsis in all 14 patients, with repetitive simultaneous contractions in eight (57%) and lower esophageal sphincter dysfunction in 12 (86%). All eight patients with lower esophageal sphincter dysfunction or incomplete relaxation of the lower esophageal sphincter on barium studies or manometry who were treated with the Clostridium botulinum toxin or endoscopic balloon dilatation had a positive response. Our preliminary data show that diffuse esophageal spasm is characterized on barium studies by frequent lower esophageal sphincter dysfunction rather than a classic corkscrew appearance. Barium and manometric studies may have complementary roles in the evaluation of patients with diffuse esophageal spasm.

Review article: Helicobacter pylori and reflux disease.

The falling prevalence of Helicobacter pylori infection and related diseases (peptic ulcer disease, gastric cancer) in developed countries has been paralleled by an increased recognition of gastro-oesophageal reflux and its complications. These epidemiological data do not support a role for H. pylori in the pathogenesis of reflux disease, but suggest a negative association with the increasing incidence of oesophageal diseases. This has led some investigators to propose a 'protective' role of H. pylori infection against the development of oesophageal diseases. In these patients, pre-existing lower oesophageal sphincter dysfunction, susceptibility to reflux, unmasking of latent reflux and the patterns and severity of gastritis are probably important factors contributing to the development of oesophageal diseases. The most likely mechanism by which H. pylori infection may protect against reflux is by decreasing the potency of the gastric refluxate in patients with corpus-predominant gastritis. The prevalence of H. pylori infection in patients with reflux disease is probably no greater than that in those without reflux, and there are conflicting data indicating that reflux symptoms or erosive oesophagitis develop after H. pylori eradication. It is also unclear whether H. pylori augments the antisecretory effects of proton pump inhibitors or accelerates the development of atrophic gastritis.

LOS Function and Obesity: The Impact of Untreated Obesity, Weight Loss, and Chronic Gastric Balloon Distension

Background/Aims: In obesity, many gastro-oesophageal reflux promoting factors are present. Weight reduction is advised to symptomatic overweight subjects. The aim of the present study was to investigate the influences of untreated obesity, weight loss, and chronic gastric balloon distension on the lower oesophageal sphincter (LOS) function. Methods: Patients entering a randomized, double-blind, sham-controlled study of balloon treatment, consisting of 4 months of either sham balloon or balloon treatment followed by 4 months of balloon treatment. Manometry and 24-hour pH measurements were performed at the start of the study and after 13 and 26 weeks. Results: Before treatment, LOS dysfunction was present in 7 of 32 patients (21.9%). Increased upright and supine reflux was present in 8 patients (25%). Sham treatment resulted in a weight loss of 9.7% with improved LOS function (a significant 0.6-cm increase in LOS length and a non-significant 2.6 mm Hg higher LOS pressure) and in a significantly decreased upright reflux (acid reflux time decreasing from 8.0 to 5.5% and number of meal-related and postprandial reflux episodes decreasing from 49 to 32). These improved values deteriorated after 4 months of balloon placement, with significantly increasing total, upright, and supine reflux to 7.5, 7.6, and 6.7% of the time, respectively, with oesophageal lesions after an overall 17.8% weight loss. Four months of balloon treatment induced a similar weight loss (9.9%) with significantly increased supine reflux from 1.6 to 6.7% of the time. After a second 4-month balloon period and an overall 13.8% weight loss, LOS and reflux values returned towards baseline values. A comparison of both groups demonstrated the adverse effects of balloon positioning after a period of substantial sham-induced weight loss. Conclusions: Impaired LOS function and increased gastro-oesophageal reflux were observed in one quarter of the untreated obese subjects. Weight loss ameliorated manometry and pH values, but subsequent balloon positioning tended to counteract these beneficial changes. In patients on balloon treatment from the start, adverse effects seemed to wear off with prolonged treatment.

Dysfunction of oesophageal motility in Helicobacter pylori-infected patients with reflux oesophagitis.

Helicobacter pylori infection has been suggested to be protective against gastro-oesophageal reflux disease. However, a significant proportion of patients with gastro-oesophageal reflux disease are infected by H. pylori. To study oesophageal motor function in H. pylori-infected patients with reflux oesophagitis. Patients with erosive reflux oesophagitis were recruited prospectively for stationary oesophageal manometry and 24-h ambulatory oesophageal pH monitoring. H. pylori status was determined by biopsy urease test. Non-reflux volunteers were recruited as controls. Seventy-four patients with erosive oesophagitis (34 H. pylori-positive, 40 H. pylori-negative) and 48 non-reflux patient controls (22 H. pylori-positive, 26 H. pylori-negative) were recruited. There was no difference in severity of oesophagitis (median grade, 1; P=0.53) or oesophageal acid exposure (total percentage time oesophageal pH < 4, 7.6% vs. 6.8%; P=0.57) between H. pylori-positive and H. pylori-negative groups. Compared to H. pylori-negative patients, H. pylori-positive patients had significantly lower basal lower oesophageal sphincter pressure (12.2 mmHg vs. 15.3 mmHg; P=0.03) and amplitude of distal peristalsis (56.9 mmHg vs. 68.4 mmHg; P=0.03). Ineffective oesophageal motility (14% vs. 7%; P=0.02) and failed oesophageal peristalsis were also significantly more prevalent in H. pylori-positive patients. Among patients with a similar degree of reflux oesophagitis, H. pylori-infected patients have more severe oesophageal dysmotility and lower oesophageal sphincter dysfunction. Oesophageal motor dysfunction probably plays a dominant role in the development of gastro-oesophageal reflux disease in patients with H. pylori infection.

Overview of the mechanisms of gastroesophageal reflux

Reflux of acidic gastric contents through the esophagogastric junction into the esophageal lumen occurs in everyone nearly every day. The esophagogastric junction is composed of several structural components that contribute to its function as the primary antireflux barrier. Only when 1 or more of these components fail does reflux esophagitis develop. The initial focus of this review is on transient lower esophageal sphincter relaxations, a vagally mediated reflex arc that accounts for almost all reflux events in healthy individuals and the majority of reflux events in those with reflux esophagitis. The association of erosive esophagitis with low or absent (incompetent) lower esophageal sphincter (LES) pressure and anatomic disruptions of the esophagogastric junction, such as hiatal hernia, are also important, especially with respect to whether the LES dysfunction and hernia are the cause or the consequence of erosive disease.

Lower Esophageal Sphincter Is Achalasic in nNOS −/− and Hypotensive in W/W v Mutant Mice

Background & Aims: It has been proposed that nitrergic nerves mediate lower esophageal sphincter (LES) relaxation with intramuscular interstitial cells of Cajal (ICC-IM) as an intermediary. Dysfunction of the nitrergic pathway has been shown to cause LES hypertension and impaired relaxation in achalasia. We determined whether mice with neuronal nitric oxide synthase gene disruption (nNOS −/−) and W/W v mice lacking ICC-IM have achalasia-like LES dysfunction. Methods: Intraluminal manometry using a customized micro-sized catheter assembly was performed in anesthetized mice. Basal LES pressure and swallow- and vagal-evoked LES relaxations were quantified in wild-type, Nω-nitro- l-arginine methyl ester HCl salt ( l-NAME)-treated, nNOS −/−, and W/W v mice. Results: Wild-type mouse LES maintained a basal pressure (24 ± 3 mm Hg; N = 8) and relaxed normally to swallow (87% ± 3%; N = 8) and vagal stimulation (91% ± 4% mm Hg; N = 6). Pretreatment with l-NAME (100 mg/kg, intravenously) attenuated LES relaxation to both stimuli ( P < 0.05). The LES in nNOS −/− was significantly hypertensive (36 ± 5 mm Hg; N = 10; P < 0.05) with a markedly impaired relaxation ( P < 0.05). In contrast, W/W v mouse LES was significantly hypotensive (11 ± 2 mm Hg; N = 6; P < 0.05) with normal relaxation that was blocked by l-NAME. Conclusions: nNOS −/− mice have LES hypertension with impaired relaxation resembling achalasia. In contrast, W/W v mice have hypotensive LES with unimpaired relaxation, suggesting that ICC-IM do not play a role in nitrergic neurotransmission.

Esophagitis-related esophageal shortening in opossum is associated with longitudinal muscle hyperresponsiveness

Acute intraluminal acid perfusion induces esophageal shortening in humans and opossums. Lower esophageal sphincter (LES) hypotension and peristaltic dysfunction occur in patients and animal models of reflux esophagitis. This study examined whether similar shortening and motor dysfunction occur in anesthetized opossums after repeated esophageal acid exposure and whether this is associated with longitudinal muscle (LM) hyperresponsiveness. Manometry used before and after 3 consecutive days of 45-min perfusion with 100 mmol/l HCl or normal saline measured esophageal length and motor responses to induced swallows. LM electrical and mechanical responses were assessed using standard isometric tension and intracellular recording techniques. Compared with controls, repeated acid perfusion induced erosive esophagitis and significant esophageal shortening, associated with enhanced LM responses to carbachol, a significantly depolarized resting membrane potential, and abnormal spike patterns. LES resting pressure and swallow-induced peristalsis were unaffected. In this model of reflux esophagitis, marked persistent esophageal shortening and associated LM hyperresponsiveness occur before significant LES or peristaltic dysfunction, suggesting that esophageal shortening is the earliest motor disorder induced by acid injury.

The anti-reflux barrier and mechanisms of gastro-oesophageal reflux

The lower oesophageal sphincter (LOS) is the major component of the anti-reflux barrier. The majority of reflux episodes occur because of intermittent brief complete lower oesophageal sphincter relaxations, transient LOS relaxations, rather than from chronic absence of LOS pressure. Recent advances in the understanding of the neural mechanisms and the receptors involved in the triggering of transient LOS relaxations have provided new insights into their control and offer the potential for the development of pharmacological therapy of reflux based on control of these events. Extrinsic support by the crural diaphragm is also important and loss of this support through development of hiatus hernia significantly compromises LOS function. This chapter reviews the components of the anti-reflux barrier, the patterns and mechanisms of LOS dysfunction underlying reflux episodes, and the interplay between sphincteric and non-sphincteric factors.

Role of esophageal body function in gastroesophageal reflux disease: implications for surgical management

Background: Effective esophageal peristalsis is a major determinant of esophageal clearance function. The relation of esophageal body function with a mechanically defective lower esophageal sphincter and the development of esophageal mucosal injury in patients with gastroesophageal reflux disease is unclear. Study Design: We analyzed the relations among the manometrically determined esophageal clearance function, lower esophageal sphincter dysfunction, esophageal acid exposure, and the presence and severity of esophageal mucosal injury in patients with gastroesophageal reflux disease. Normal values for the manometric assessment of esophageal clearance function were established in 50 normal volunteers and subsequently applied to 160 symptomatic patients with increased esophageal exposure to gastric juice and various grades of esophageal mucosal injury (no minimal surgery, esophagitis, stricture, and Barrett’s esophagus). Results: Defective clearance function was present in 47.5% of the patients; a defective lower esophageal sphincter was documented in 63.1%. Compromised esophageal clearance function was significantly more common in patients with a defective lower esophageal sphincter than in those with normal sphincter function (55% versus 33.8%). Esophageal acid exposure time and the prevalence and severity of esophageal mucosal injury were highest in patients with a defective sphincter and compromised clearance function. Conclusions: These data show that esophageal motor function deteriorates with increasing severity of mucosal injury. This appears to be due to persistent reflux of gastric juice across a mechanically defective lower esophageal sphincter. This may influence the choice and outcome of antireflux surgery. Surgical correction of a mechanically defective sphincter before the loss of esophageal body function is advocated.

Treatment of symptomatic nonachalasia esophageal motor disorders with botulinum toxin injection at the lower esophageal sphincter.

The purpose of this study was to determine if botulinum toxin injection at the lower esophageal sphincter improves symptoms in patients with nonachalasia spastic esophageal motility disorders. Fifteen patients with nonachalasia spastic esophageal motility disorders (diffuse esophageal spasm, nonspecific esophageal motility disorders, and lower esophageal sphincter dysfunction) unresponsive to medical therapy underwent endoscopic injection of botulinum toxin at the level of the gastroesophageal junction. Symptoms were scored (0 = no symptoms, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe) before treatment, at seven days and every 30 days after treatment. There was significant improvement in chest pain, dysphagia, and regurgitation at 7,30,60 and 90 days after treatment. At one month after treatment, 11 of 15 (73%) patients had a good or excellent response to treatment. At the last patient interview (mean follow-up of 10.6 months), five (33%) patients continued to have a good to excellent response, whereas 10 (67%) underwent subsequent treatment with repeat botulinum toxin, pneumatic dilation, or bougienage. We conclude that botulinum toxin injection at the gastroesophageal junction leads to significant symptom improvement in patients with nonachalasia esophageal motility disorders. These results suggest that botulinum toxin may be an effective treatment option in some of these patients not responsive to conventional medical therapy.

Atypical Manometric Abnormality of the Lower Esophageal Sphincter: A Procedure-Related, Stress-Induced Phenomenon?

Stress-induced esophageal contraction abnormalities have been well documented in the literature, but relatively little is known about stress-related lower esophageal sphincter (LES) dysfunction. Two patients are described in whom initial manometry studies revealed LES hypertension and impaired LES relaxation. Both patients were markedly anxious and agitated during the initial study. However, when the manometry was repeated with the patients in a calmer state, LES pressure and function were normal. These cases demonstrate the need to be aware of stress-related LES dysfunction. If this phenomenon is not identified in the appropriate settings, it could lead to significant errors in management.

Lower esophageal sphincter dysfunction precludes safe gastric feeding after head injury.

Early nutrition is advocated for patients with head injury to counter the postinjury hypermetabolic state. The gastric route of feeding often leads to vomiting and aspiration pneumonitis. This study was designed to identify the role of lower esophageal sphincter (LES) function in this complication. The LES function was assessed within 72 hours of admission in 16 patients with a head injury and a Glasgow Coma Scale (GCS) score less than 12 (range, 3-11). Other admission assessments included an APACHE II score of 11.7, Injury Severity Score (ISS) of 30.5, and a Revised Trauma Score (RTS) of 6.4. These studies were repeated 1 week postinjury in five patients. Dysfunction of the LES was present in all 16 patients; the average gastric-to-esophageal pressure difference was -0.49 mm Hg (range, -0.59 to 2.5) compared with a normal value of greater than 20 mm Hg. The five patients restudied at 1 week had a gastric-to-esophageal pressure difference of 13.3 mm Hg (range, -3.4 to 36.6 mm Hg). The single patient with a GCS score below 12 at 1 week had a low LES tone. These data show that LES dysfunction accompanies acute head injury and contributes to aspiration pneumonitis after early gastric feeding. Nutrition in patients with low GCS scores should be parenteral or via the jejunum.

Gastroesophageal reflux disease

Gastroesophageal reflux disease is a very common condition that is usually manifested by heartburn or regurgitation. Reflux esophagitis, caused by mucosal exposure to the backflow of caustic gastric contents, is primarily a result of lower esophageal sphincter dysfunction. Diagnostic workup varies but commonly includes esophagoscopy, 24-hour esophageal pH monitoring, and radiography of the upper gastrointestinal tract. Treatment, which progresses from simple life-style changes and antacids to histamine2 receptor antagonists to omeprazole (Prilosec) or surgery, is tailored to individual needs and is generally successful.