Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa.

BACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα+ cells without a significant change in ICCs.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare.

A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis.

BACKGROUND: Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis. METHODS: A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n = 22), 20-mg (n = 21), 40-mg (n = 23) TZP-102 or placebo (n = 26). The primary endpoint was the change from baseline in gastric half-emptying time (T(½)) utilizing (13)C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE). KEY RESULTS: Gastric T½ changes were not statistically significant between TZP-102 and placebo after 28 days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1 week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes. CONCLUSIONS & INFERENCES: TZP-102 for 28 days, at doses of 10-40 mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.

Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data.

BACKGROUND: Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis. AIM: To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of ≥3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale. METHODS: Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 µg/kg) or placebo. Efficacy was assessed by symptom improvement. RESULTS: At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45±0.44. Statistically significant improvements over placebo occurred in the 80 µg/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82±0.76, P=0.011) and the GCSI Total score (-3.14±0.78, P=0.016) and were maintained at the 30-day follow-up assessment (-2.02±1.63, P=0.073 and -1.99±1.33, P=0.032 respectively). The proportion of days with vomiting was reduced significantly (P=0.05) in the 80 µg/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days). CONCLUSIONS: TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis.

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.

BACKGROUND: The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. METHODS: Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. KEY RESULTS: Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. CONCLUSIONS & INFERENCES: The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.

Pharmacokinetic profile of immediate-release omeprazole in patients with gastro-oesophageal reflux associated with gastroparesis.

BACKGROUND: Immediate-release omeprazole has a more rapid absorption compared with delayed-release omeprazole in asymptomatic volunteers. However, effects of delayed gastric emptying on omeprazole absorption remain unknown. AIM: To compare pharmacokinetics between immediate and delayed-release omeprazole in patients with GERD associated with gastroparesis. METHODS: Open-label, randomized, cross-over study was performed. Antireflux and prokinetic medications were discontinued. Subjects were randomized into: (i) Immediate-release omeprazole 40 mg suspension o.m. for 7 days, wash-out for 10-14 days, followed by delayed-release omeprazole 40 mg capsule o.m. for 7 days, or (ii) the same schedule in reverse order. On day 7, omeprazole concentrations were obtained before and up to 5 h after taking the study drug. Patient Assessment of GI Disorders-Symptom Severity Index was obtained. RESULTS: A total of 12 women (mean age 51 years) completed the protocol. Time to maximal omeprazole concentration was significantly shorter for omeprazole. Maximal concentration was significantly greater for omeprazole, but total area under concentration-time curves was similar. Pharmacokinetic profile was less variable for immediate compared with delayed-release omeprazole. CONCLUSIONS: Immediate-release omeprazole was associated with a more rapid absorption and less variable pharmacokinetic profile compared with delayed-release omeprazole in reflux patients associated with gastroparesis.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects.

BACKGROUND: Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). AIMS: To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. METHODS: Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [(99m)Tc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. RESULTS: Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. CONCLUSION: SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.

Comparison of methylene blue-directed biopsies and conventional biopsies in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a preliminary study.

BACKGROUND: The diagnostic advantage of methylene blue (MB) chromoendoscopy in Barrett's esophagus is unclear. METHODS: Patients with columnar-lined esophagus (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed biopsy versus conventional biopsy. RESULTS: Forty-seven patients (19 long-segment CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy. Sensitivity and specificity of MB for specialized intestinal metaplasia were 53% and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51% and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short-segment CLE) completed the crossover trial. Relative frequencies for specialized intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy specimens, respectively (p = 0.73). Relative frequencies for dysplasia were 20% and 18% from MB-directed and conventional biopsy specimens, respectively (p = 0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients with MB and 7 patients with conventional biopsy methods (p = 0.25). The number of biopsy specimens per EGD was greater with MB, which may have influenced the diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly all of the dysplastic specimens. CONCLUSIONS: Results of MB-directed biopsy were similar to conventional biopsy in detecting specialized intestinal metaplasia and indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's esophagus.

Current medical and surgical treatment options for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common disorders in medicine. The options of medical versus surgical therapies have been highlighted by more potent acid suppression medications and by the introduction of minimally invasive surgery for GERD. Many factors will impact on the treatment selection for each individual patient: the underlying pathophysiology, typical vs atypical symptoms, presence of reflux complications, and success and limitations of medical and surgical treatments. Medical antireflux therapy is very effective and safe, but long-term maintenance therapy is required for most patients. Minimally invasive antireflux surgery has provided excellent results, but outcome is dependent on patient selection and surgical expertise. Careful pre-operative evaluation is essential to determine the optimal treatment and surgical approach.

Supraesophageal manifestations of gastroesophageal reflux disease.

An increasing amount of evidence indicates that gastroesophageal reflux disease (GERD) is a contributing factor to hoarseness, throat clearing, throat discomfort, chronic cough, and shortness of breath. The association between GERD and these supraesophageal symptoms may be elusive. Heartburn and regurgitation are absent in more than 50% of patients. Acid reflux should be considered if signs of GERD are present, symptoms are unexplained, or symptoms are refractory to therapy. The diagnosis of GERD may be unclear, despite a careful history and initial evaluation. A high index of suspicion is required to make the diagnosis. An empiric trial of antireflux therapy is appropriate when GERD is suspected. Multiprobe ambulatory pH monitoring is currently the diagnostic test of choice, but the level of sensitivity and specificity for supraesophageal manifestations of GERD is uncertain. Response to antireflux therapy is less predictable than typical GERD. More intensive acid suppression and longer treatment duration are usually required.

NSAIDs, aspirin, and esophageal strictures: are over-the-counter medications harmful to the esophagus?

There are several studies that suggest that aspirin (acetylsalicylic acid [ASA]) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with esophagitis or esophageal stricture formation. There are limited data on the potential of low-dose ASA and over-the-counter (OTC) NSAIDs to cause esophageal injury. The goal of this study was to determine whether there is an association between esophageal strictures and ASA/NSAID use, including low-dose ASA and OTC NSAIDs. A total of 79 consecutive patients (mean age, 52.8 years; 38 men, 41 women) referred for endoscopy from 4/1/96 to 11/15/96 for chronic gastroesophageal reflux disease symptoms were evaluated. Data collected include gender, race, and age, NSAID or ASA use, as well as an assessment of dysphagia, heartburn duration, and heartburn frequency. Patients taking NSAIDs or ASA at least twice a week were considered ASA/NSAID users. There were 46 patients without strictures and 33 patients with peptic strictures. Patients with strictures were older than patients without strictures (mean age, 58.7 versus 48.6 years; p < 0.01), had longer duration of heartburn symptoms (8.6 versus 6.4 years, p < 0.05), and were more likely to have mucosal injury (50% versus 26.1%). Stricture patients were more likely to use ASA/NSAIDs (63.6% versus 26.1%; p < 0.01). In particular, stricture patients were more likely to use low-dose ASA than patients without strictures (30.3% versus 2.2%; p < 0.01). Otherwise, there were no significant differences with regard to gender, race, or heartburn duration or frequency. Linear regression analysis showed that ASA/NSAID use had a greater influence on the incidence of peptic strictures than age. There is an association between esophageal stricture and ASA/NSAID use, which includes OTC NSAIDs and low-dose ASA.

Racial differences in the histology, location, and risk factors of esophageal cancer.

Although esophageal cancer is uncommon in the united states, its high mortality rate and recent increased incidence make it an important malignancy. Because there appears to be significant racial variation in the types of esophageal cancer, we examined a group of black patients with esophageal cancer and compared their risk factors, histology, and location with those of a cohort of white patients with esophageal cancer seen during the same period. We retrospectively reviewed patients with esophageal cancer seen at three major hospitals in Atlanta, Georgia from January 1990 to April 1996. Patients of races other than white or black were excluded from this study, the esophagus was separated into upper, middle, and lower thirds by defined criteria. Of the eligible 234 patients, 129 were black and 105 were white. In blacks with esophageal cancer, squamous cell cancer was the predominant type (92%), and adenocarcinoma was infrequent in whites, adenocarcinoma was more common than squamous cell cancer (66% vs. 32%). Although Barrett's esophagus was distinctly uncommon, smoking and alcohol consumption were significantly more common in blacks. Only 43% of the patients with adenocarcinoma had evidence of barrett's esophagus, all adenocarcinomas were located in the lower third of the esophagus. There appear to be significant racial differences in the types, risk factors, and location of esophageal cancer. Adenocarcinoma and Barrett's esophagus are uncommon in blacks.

Laparoscopic antireflux surgery in the elderly.

OBJECTIVE: Laparoscopic antireflux surgery is indicated in young patients with medication-dependent gastroesophageal reflux disease (GERD), both because of their need for lifelong medical treatment and the need to prevent the complications of GERD. Many elderly patients with GERD have similar concerns. We compared the safety and efficacy of laparoscopic antireflux surgery in the elderly with the results achieved in patients <65 yr. METHODS: A total of 359 patients have had laparoscopic antireflux surgery in our hospital, 42 of whom were > or = 65 yr of age. Symptoms were scored from 0 (none) to 4 (severe) before and after surgery. Ambulatory pH monitoring was also performed before and after surgery. Results were compared between age groups with the Mann-Whitney U test. RESULTS: Elderly patients had significantly higher preoperative American Society of Anesthesiologists (ASA) scores (mean 2.4 vs 2.0) (p = 0.0024), but otherwise there were no significant differences in preoperative symptom scores or pH results. Both groups demonstrated equivalent postoperative improvement in symptoms and 24-h pH study. There was no mortality in either group, and there was no significant difference in morbidity or hospital stay between the two groups. CONCLUSION: Laparoscopic antireflux surgery is a safe and effective treatment of GERD in the elderly and should not be refused solely on the basis of age.

The prevalence of intestinal metaplasia in patients with and without peptic strictures.

OBJECTIVE: Several studies suggest that patients with esophageal peptic strictures have a high prevalence of Barrett's esophagus. However, these studies did not include appropriate control groups, were retrospective in nature, or did not strictly define Barrett's esophagus. Our aim was to compare the prevalence of Barrett's esophagus in patients with and without gastroesophageal reflux disease strictures in a prospective study. METHODS: Seventy-nine patients referred for endoscopy for gastroesophageal reflux disease symptoms were evaluated. We collected demographic information and an esophageal symptom assessment. Biopsy specimens were obtained from peptic strictures, Schatzki rings, or from any areas of columnar-lined esophagus or mucosal injury. Barrett's esophagus was strictly defined as the presence of intestinal metaplasia from tubular esophagus. RESULTS: There were 46 patients without strictures and 28 patients with peptic strictures. Five patients had Schatzki's rings. The prevalence of intestinal metaplasia was 23.9% in patients without strictures, and 25% in patients with peptic strictures (p = NS). There was no difference in prevalence of short- or long-segment Barrett's esophagus between the groups. Patients with strictures were older than patients without strictures (mean age 58.9 vs 48.6 yr), and more likely to have mucosal injury (50% vs 26.1%). Otherwise, there were no significant differences with regards to gender, race, heartburn duration or frequency. CONCLUSIONS: Barrett's esophagus, as defined by the presence of intestinal metaplasia in the tubular esophagus, is equally common in patients with and without peptic strictures. There does not appear to be an association between Barrett's esophagus and peptic strictures.

Dual-channel ambulatory esophageal pH monitoring. A useful diagnostic tool?

Ambulatory pH monitoring of the distal esophagus is the most accurate diagnostic study for patients with suspected gastroesophageal reflux disease (GERD). The measurement of proximal esophageal acid exposure time may be useful in patients with atypical reflux symptoms. The aim of this study is to evaluate if proximal esophageal pH monitoring provides useful information beyond that learned with distal esophageal pH monitoring. We routinely performed dual-channel pH monitoring with pH electrodes positioned at 20 and 5 cm above the manometric lower esophageal sphincter from January 1992 to August 1995. All patients scored their esophageal symptoms from zero (none) to four (severe). We compared proximal esophageal reflux (PR) in patients with typical symptoms (i.e., heartburn, regurgitation) and in patients with atypical symptoms (i.e., chest pain, cough, hoarseness, and asthma). We compared symptom profiles between patients with and without PR. We reviewed our experience in patients with abnormal PR, but with a normal amount of distal esophageal reflux (DR). We studied 441 consecutive patients. There were no significant differences in PR between patients with typical and atypical symptoms. There were no differences in symptom profiles between patients with normal and abnormal PR. There were no differences of PR between the different atypical symptoms. PR did not correlate with the severity of the patient's symptoms. PR correlated well only with DR. Twenty-four patients had isolated abnormal PR, but only six patients improved with antireflux therapy. We conclude that routine ambulatory esophageal pH monitoring of the proximal esophagus appears to be of little value. The decision to offer patients an empiric trial of antireflux therapy for suspected GERD should not be based on the presence or absence of PR.

Empiric trial of high-dose omeprazole in patients with posterior laryngitis: a prospective study.

UNLABELLED: The optimal management of patients suspected with gastroesophageal reflux-related posterior laryngitis is unclear. History, physical examination, and ambulatory pH monitoring all have significant limitations in identifying patients who will respond to antireflux therapy. OBJECTIVE: To evaluate the merit of empiric omeprazole therapy in patients with posterior laryngitis. METHODS: Twenty-two patients (11 men/11 women, median age 58 yr) with newly diagnosed posterior laryngitis were enrolled. All had persistent laryngeal symptoms for at least 1 month. An empiric trial of omeprazole at 40 mg q.h.s. was given for 8 wk. Four laryngeal symptoms (hoarseness, throat burning/pain, throat clearing, and cough) and four esophageal symptoms (heartburn, regurgitation, dysphagia, and odynophagia) were scored from 0 to 3. Symptom scores were obtained before, 4 wk after, and 8 wk after the start of omeprazole. Patients were classified as responders if they were symptom free or satisfied with results. Omeprazole was stopped in the responders to look for relapse. Ambulatory pH monitoring was performed in patients who did not respond. RESULTS: One patient discontinued omeprazole and withdrew from the study. In the remaining 21 patients, the total laryngeal and esophageal symptom scores significantly improved after empiric omeprazole. Fourteen patients (67%) were classified as responders. Eight patients (38%) had a relapse when omeprazole was stopped. Six patients (29%), interestingly, did not relapse and did not require long-term antireflux therapy. Seven patients (33%) were classified as nonresponders. Ambulatory pH monitoring was abnormal in four of the five patients who agreed to have this test. Increasing the dose of omeprazole to 40 mg b.i.d. provided no additional benefit in the nonresponders. CONCLUSIONS: Empiric omeprazole therapy is a reasonable, initial approach to patients with suspected gastroesophageal reflux-related posterior laryngitis. A significant number of patients do well with a short course of antireflux therapy. Additionally, a third of the patients may not completely respond to intensive medical therapy despite the fact that reflux is documented.

Medical therapy of gastroesophageal reflux and management of esophageal strictures.

The goals of modern medical therapy for gastroesophageal reflux disease are threefold: first, eliminate symptoms; second, heal injured esophageal mucosa; third, manage and/or prevent complications. Selection of a particular medical regimen depends on the severity of the disease, effectiveness of the therapy, cost, and convenience of the medical regimen. An accurate diagnosis needs to be made in patients suspected with esophageal strictures. If there is a treatable underlying disease, specific therapy is essential. The goal of dilation therapy should be established and set about to accomplish in a timely, but unhurried fashion. Fluoroscopy and wire-guided dilators should be used liberally, especially for difficult strictures.

Cervical esophageal web caused by an inlet patch of gastric mucosa.

A 55-year-old woman had chronic, progressive dysphagia. An esophageal web in the cervical esophagus was identified by barium swallow and endoscopy. At endoscopy, an inlet patch of gastric mucosa was identified in proximity to the cervical web. It is believed that gastric acid production from the inlet patch led to development of the cervical esophageal web. We present our patient's case and review the literature relevant to this topic.

Significance of intestinal metaplasia in different areas of esophagus including esophagogastric junction.

Over the past two decades, the incidence of adenocarcinoma of the esophagus and gastric cardia has increased at a rate exceeding that of any other cancer. Barrett's esophagus is the only known risk factor for these malignancies. Recently, emphasis has been placed on the significance of specialized intestinal metaplasia (SIM) on esophageal biopsies. Our aim was to compare the prevalence of SIM at different esophageal locations in patients who are at higher risk of developing esophageal adenocarcinoma (Caucasians) and patients with lower risk of developing esophageal adenocarcinoma (African-Americans). Eighty-seven unselected patients (42 Caucasians and 45 African-Americans) underwent routine upper endoscopy with biopsies from the proximal margin of columnar mucosa. We classified patients into those with a columnar-lined esophagus with SIM (CLE with SIM); CLE without SIM; or SIM with a normal-appearing gastroesophageal junction (SIM-GEJ). The prevalence of CLE with SIM, CLE without SIM, and SIM-GEJ was 28%, 10%, and 10% in Caucasians compared to 0%, 18% and 11% in African-Americans (P = 0.0001, 0.26, and 0.81, respectively). We found CLE with SIM only in patients with reflux symptoms at least twice a week. It is concluded that CLE with SIM is seen most commonly in patients thought to be at risk for esophageal adenocarcinoma (Caucasians with reflux symptoms). It is rarely seen in other groups with lower risk for this malignancy (African-Americans, nonrefluxers). Conversely, SIM-GEJ and CLE without SIM are common in all groups and are of questionable significance.