Esophageal Lichen Planus Is Associated With a Significant Increase in Risk of Squamous Cell Carcinoma.

Esophageal lichen planus (ELP) is a chronic inflammatory process characterized by apoptotic activity of cytotoxic CD8+ T cells on basal keratinocytes as well as regulatory and helper T cells.1-3 Due to chronic inflammation, malignant transformation may be a concern and has been documented in case reports.4,5 We describe the occurrence of esophageal cancer in ELP patients from a large tertiary patient population.

The diagnosis of esophageal eosinophilia is not increased in the summer months.

Smaller studies have suggested seasonal variation of the diagnosis of eosinophilic esophagitis with more patients being diagnosed in the aeroallergen season. We evaluated a large group of adult patients for a seasonal variation of the diagnosis of symptomatic eosinophilic esophageal infiltration. We performed a retrospective review of adult patients from a large Eosinophilic esophagitis database at the Mayo Clinic Rochester. We only included patients from three states in the upper Midwest, who had 15 or more eosinophils per high-power field on esophageal biopsy, symptomatic dysphagia, and were seen, in our Gastroenterology Clinic between 2000 and 2008. Clinical data were abstracted and the month of diagnosis was determined. The Rayleigh circular test and the Chi-square goodness-of-fit test were used to detect seasonality of symptomatic esophageal eosinophilia diagnosis and seasonality corrected for esophagogastroduodenoscopy monthly volume. The diagnosis of symptomatic eosinophilic esophageal infiltration was made in 372 patients. The mean number of eosinophils was 39.6 per high-power field. The December/January and May/June periods seem to have an increased presentation rate (p = 0.014). Of those tested, reactions to any aeroallergen was present in 69 % (48/70), reactions to >4 aeroallergens in 47 % (33/70) and reactions to any food allergen in 63 % (50/80) of patients. There was no evidence of monthly concentration of symptomatic esophageal eosinophilia diagnosis in the subgroups of patients with any positive aeroallergen, >4 positive aeroallergens, or history of atopy. The diagnosis of symptomatic esophageal eosinophilia is not made more frequently in the summer months.

Once-daily omeprazole/sodium bicarbonate heals severe refractory reflux esophagitis with morning or nighttime dosing.

BACKGROUND: Morning dose or twice-daily proton pump inhibitor (PPI) use is often prescribed to heal severe reflux esophagitis. AIM: Compare the effect of single dose morning (control arm) versus nighttime (experimental arm) omeprazole/sodium bicarbonate (Zegerid(®)) (IR-OME) on esophagitis and gastroesophageal reflux symptoms. METHODS: Adult outpatients with Los Angeles grade C or D esophagitis were allocated to open-label 40 mg IR-OME once a day for 8 weeks in a prospective, randomized, parallel design, single center study. Esophagogastroduodenoscopy (EGD) and validated self-report symptom questionnaires were completed at baseline and follow-up. Intention-to-treat and per-protocol analyses were performed. RESULTS: Ninety-two of 128 (72 %) eligible subjects participated [64 (70 %) male, mean age 58 (range 19-86), median BMI 29 (range 21-51), 58 C:34 D]. Overall, 81 (88 %) subjects healed [n = 70 (76 %)] or improved [n = 11 (12 %)] erosions. There was no significant difference (morning vs. night) in mucosal healing [81 vs. 71 %, (p = 0.44)] or symptom resolution [heartburn (77 vs. 65 %, p = 0.12), acid regurgitation (82 vs. 73 %, p = 0.28)]. Prevalence of newly identified Barrett's esophagus was 14 % with half diagnosed only after treatment. CONCLUSIONS: Once-daily IR-OME (taken morning or night) effectively heals severe reflux esophagitis and improves GERD symptoms. Results support the clinical practice recommendation to repeat EGD after 8 weeks PPI therapy in severe esophagitis patients to assure healing and exclude Barrett's esophagus.

Swallowed fluticasone improves histologic but not symptomatic response of adults with eosinophilic esophagitis.

BACKGROUND & AIMS: We evaluated the effect of aerosolized fluticasone therapy on symptomatic dysphagia and histologic eosinophilia in adults with eosinophilic esophagitis (EoE). METHODS: We performed a double-blind, randomized, placebo-controlled trial of fluticasone in 42 adult patients with a new diagnosis of EoE (30 men; mean age, 37.5 y). Participants were assigned randomly to groups that swallowed 880 µg of aerosolized fluticasone twice daily (n = 21), or took a placebo inhaler twice daily (n = 15) for 6 weeks. End points of the study were symptomatic and histologic response. RESULTS: A complete histologic response (>90% decrease in mean eosinophil count) was observed in 11 of 15 subjects who received 6 weeks of fluticasone (62%), compared with none of the 15 subjects who received placebo (P < .001), based on intention-to-treat analysis; histologic responses were observed in 68% of subjects who received fluticasone (13 of 19) compared with none of those who received placebo (0 of 15) by per-protocol analysis (P < .001). Intracellular staining for eosinophil-derived neurotoxin was reduced in 81% of subjects who received fluticasone (13 of 16) compared with 8% who received placebo (1 of 13) (P < .001). Dysphagia was reduced in 57% of subjects who received fluticasone (12 of 21) compared with 33% who received placebo (7 of 21) (P = .22) by intention-to-treat analysis; dysphagia was reduced in 63% of patients who received fluticasone (12 of 19) and 47% of those who received placebo (7 of 15) (P = .49) based on per-protocol analysis. Esophageal candidiasis developed in 26% of subjects who received fluticasone (5 of 19), but in none of the subjects in the placebo group (P = .05). CONCLUSIONS: Aerosolized, swallowed fluticasone leads to a histologic but not a symptomatic response in adults with EoE.

Factors that predict relief from upper abdominal pain after cholecystectomy.

BACKGROUND & AIMS: Upper abdominal pain (UAP) in patients with gallstones is often treated by cholecystectomy but it frequently persists. We aimed to identify symptoms associated with relief. METHODS: We followed 1008 patients who received cholecystectomy for gallstones and UAP at the Mayo Clinic (Rochester, Minnesota) or Kaiser Permanente (San Diego, California) for 12 months. A validated, self-completed biliary symptoms questionnaire identified features of UAP, gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS); the questionnaire was given initially and 3 and 12 months after cholecystectomy, to identify features that predicted sustained relief of UAP. RESULTS: Five hundred ninety-four patients (59%) reported relief from UAP. Factors associated univariately (P < .05) with relief included frequency of UAP ≤1 per month, onset ≤1 year preoperatively, usual duration (30 minutes to 24 hours, most often in the evening or night), and severity >5/10. Compared to no features, multiple predictive features of UAP (frequency, onset, duration, or timing) were associated with increasing odds ratios (95% confidence interval) for relief: 1, 2, or 3 features (4.2 [1.1-16]; P = .03) and 4 features (6.3 [1.6-25]; P = .008). Negative univariate associations included lower abdominal pain (LAP), usual bowel pattern, nausea ≥1 per week, often feeling bloated or burpy, GERD, and/or IBS. There was an inverse association between relief and somatization; relief was not associated with postprandial UAP. Multivariable logistic regression analysis revealed independent associations (P < .05) with UAP frequency, onset, and nocturnal awakening, but inverse associations with lower abdominal pain, abnormal bowel pattern, and frequent bloated or burpy feelings. CONCLUSIONS: UAP features and concomitant GERD, IBS, and somatization determine the odds for relief from UAP after cholecystectomy.

Does gastric resection have a role in the management of severe postfundoplication gastric dysfunction?

BACKGROUND: Bloating, flatulence, early satiety, and dysphagia resolve in more than 90% of patients early after fundoplication. Gastric dysfunction can persist, however, and a small number of patients develop severe gastric dysfunction (gastroparesis). Management of gastroparesis after antireflux procedures is generally conservative, but gastroparesis can become refractory to medical therapy. The aim of this study was to assess the role of gastric resection in the management of the unusual patient with severe postfundoplication gastric dysfunction. METHODS: From January 1990 to October 2010, a total of 5,129 gastric resections were performed at our institution. From this cohort, we identified nine patients with postfundoplication gastric dysfunction managed with gastric resection. Clinical records were reviewed retrospectively for preoperative evaluation, perioperative course, and long-term outcomes. RESULTS: Over 20 years, nine patients were treated with gastric resection for debilitating gastric dysfunction after antireflux surgery. Seven of the nine patients were female; the median preoperative body mass index was 25 kg/m(2) (18-31 kg/m(2)). Median follow-up was 23 months (1-97 months). Preoperatively, five patients required enteral feeding. Postoperatively, although there were no deaths, one patient required operative drainage of a subphrenic abscess, one developed temporary respiratory failure, and one was readmitted for partial small bowel obstruction. Six of the nine patients maintain their nutrition orally, but three are maintained with enteral nutrition. Only two patients are subjectively asymptomatic. CONCLUSIONS: Outcomes after gastric resection for postfundoplication gastric dysfunction are poor, with three of the nine patients requiring supplemental nutrition and seven of the nine having persistent symptoms.

Low grade esophageal eosinophilia in adults: an unrecognized part of the spectrum of eosinophilic esophagitis?

BACKGROUND: Eosinophilic esophagitis (EoE) is defined by a minimum of 15 eosinophils (eos) per high-powered field (HPF) on esophageal biopsy, along with esophageal symptoms and the exclusion of gastroesophageal reflux (GERD). The clinical significance of fewer eosinophils is unknown. METHODS: Fifty-nine adult patients without a previous diagnosis of EoE with esophageal biopsies containing 1-14 eos per HPF (low grade eosinophilia) and 418 adult patients with ≥15 eos per HPF were identified by retrospective review. Patients were divided into group A (1-9 eos per HPF), group B (10-14 eos per HPF), and group C (≥15 eos per HPF) with a chart review of clinical and demographic data. RESULTS: While dysphagia and atopy (asthma and allergic rhinitis) were more common in patients with ≥15 eos per HPF (group C) than those with low grade esophageal eosinophilia (groups A and B) (93 vs. 88%, P = 0.02), food impaction and heartburn occurred at an equal frequency across all patient groups. Endoscopic findings were likewise similar between groups. Of the 14 patients with low grade esophageal eosinophilia who underwent repeat endoscopy a mean interval of 42 weeks (range 8-118 weeks) later, five (36%) met conventional diagnostic criteria for EoE of 15 or greater eos per HPF. Follow-up in ten patients treated with topical corticosteroids noted improvement in nine, with mean follow-up of 8 weeks (range 4-12 weeks). CONCLUSION: Some adult patients with dysphagia and less than 15 eos per HPF have similar endoscopic findings and clinical course to patients meeting the consensus definition of EoE. Further evaluation of patients with low grade esophageal eosinophilia is needed.

Occurrence of and risk factors for complications after endoscopic dilation in eosinophilic esophagitis.

BACKGROUND: Several small series have suggested an increased risk of complications associated with esophageal dilation in patients with eosinophilic esophagitis (EoE). OBJECTIVE: To quantitate the risk and identify risk factors for esophageal complications in dilation in EoE patients. DESIGN: Retrospective, uncontrolled, single-center study. SETTING: Tertiary referral hospital. PATIENTS: A total of 161 EoE patients (mean ± standard deviation age 44.3 ± 15.3 years, 112 men, 49 women, 150 white patients, 10 unknown, 1 Asian). INTERVENTIONS: Through-the-scope balloon or Savary dilation of EoE. MAIN OUTCOME MEASUREMENTS: The rate of complications defined as deep mucosal tear, major bleeding, or perforation, and determination of risk factors for complications. RESULTS: A total of 293 dilations were performed in 161 patients. Complications reported were deep mucosal tear in 9.2% (n = 27), major bleeding in 0.3% (n = 1), and immediate perforation in 1.0% (n = 3). All patients with perforations were successfully treated medically without surgery (mean ± standard deviation hospital stay 5.3 ± 3.2 days). Factors associated with an increased risk of complications were luminal narrowing in the upper (odds ratio [OR], 5.62; 95% CI, 2.07-15.26; P < .001) and middle third of the esophagus (OR, 4.93; 95% CI, 1.64-14.83; P < .005) compared with lower third, luminal stricture unable to be traversed with a standard upper endoscope (OR, 2.48; 95% CI, 1.06-5.83; P = .037), and use of Savary dilator (OR, 2.63; 95% CI, 1.18-5.83; P = .018). LIMITATIONS: Retrospective design, uncontrolled study. CONCLUSIONS: Deep mucosal tears are common after dilation (9%), but the risk of immediate transluminal perforation with EoE is approximately 1%. The risk of severe complications is increased in patients with more proximal stricture and strictures that initially prevent endoscope passage.

The Mayo Dysphagia Questionnaire-30: documentation of reliability and validity of a tool for interventional trials in adults with esophageal disease.

The aim of this study was to develop the Mayo Dysphagia Questionnaire-30 Day (MDQ-30), a tool to measure esophageal dysphagia, by adapting items from validated instruments for use in clinical trials, and assess its feasibility, reproducibility, and concurrent validity. Outpatients referred to endoscopy for dysphagia or seen in a specialty clinic were recruited. Feasibility testing was done to identify problematic items. Reproducibility was measured by test-retest format. Concurrent validity reflects agreement between information gathered in a structured interview versus the patients' written responses. The MDQ-30, a 28-item instrument, took 10 min (range = 5-30 min) to complete. Four hundred thirty-one outpatients [210 (49%) men; mean age = 61 years] participated. Overall, most concurrent validity kappa values for dysphagia were very good to excellent with a median of 0.78 (min 0.28, max 0.95). The majority of reproducibility kappa values for dysphagia were moderate to excellent with a median kappa value of 0.66 (min 0.07, max 1.0). Overall, concurrent validity and reproducibility kappa values for gastroesophageal reflux disease (GERD) symptoms were 0.81 (95% CI = 0.72, 0.91) and 0.66 (95% CI = 0.55, 0.77), respectively. Individual item percent agreement was generally very good to excellent. Internal consistency was excellent. We conclude that the MDQ-30 is an easy-to-complete tool to evaluate reliably dysphagia symptoms over the last 30 days.

Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis.

OBJECTIVES: Eosinophilic esophagitis (EoE) is characterized by infiltration of eosinophils into esophageal epithelium. Blood levels of an eosinophil granule protein, eosinophil-derived neurotoxin (EDN), have been proposed as a biomarker for EoE. However, information regarding localization of EDN in the diseased tissues has not been available. The goal of this study was to evaluate the magnitude and distribution of EDN deposition in tissue specimens from the esophagus of EoE patients. METHODS: We studied specimens from 10 adult EoE patients and eight histologically normal controls (three under age 17). Sections from mid-esophageal biopsy specimens were stained for EDN by immunofluorescence, using a polyclonal rabbit antibody to EDN. Cellular staining (i.e., infiltration of intact eosinophils) and extracellular staining (i.e., deposition of released EDN) were scored in a blinded manner on an established 7-point scale. RESULTS: Esophageal biopsy specimens from histologically normal controls showed no or few intact eosinophils and no or minimal extracellular EDN deposition. In contrast, EDN staining was clearly observed in specimens from all EoE patients. In some EoE patients, marked extracellular EDN deposition was observed despite relatively small numbers of intact eosinophils. Overall, there was no correlation between the eosinophil infiltration and the extracellular EDN staining scores. CONCLUSIONS: Marked tissue deposition of extracellular EDN is present in the esophagus of EoE patients. Tissue eosinophil counts may underestimate how extensively eosinophils are involved, particularly in individuals with marked eosinophil degranulation. Evaluation of EDN staining in esophageal biopsy specimens may be useful to diagnose and manage patients with EoE.

3-yr-follow-up of topical corticosteroid treatment for eosinophilic esophagitis in adults.

BACKGROUND: Eosinophilic esophagitis (EE) is a clinicopathologic syndrome comprising isolated eosinophilic inflammation of the esophagus, with symptoms of dysphagia, and possibly, reflux. It was initially described in children, and in recent years, there is a heightened awareness in adults. The etiology is not completely understood. The treatments include dietary manipulation, topical corticosteroids, systemic corticosteroids, Montelukast, and endoscopic dilation. In adults, there are no randomized trials demonstrating the efficacy of any particular treatment, and no prospective studies describing the natural history of the disease following treatment. METHODS: We performed an interval follow-up of patients treated with a swallowed corticosteroid inhaler. We contacted 51 adult patients who were diagnosed with EE and treated with a swallowed corticosteroid inhaler between September 1, 1999, and May 31, 2003. All patients had received 6 wk of treatment with fluticasone 220 mEq/puff, four puffs swallowed twice daily for 6 wk. RESULTS: Thirty-two patients replied (63%) with a mean follow-up duration of 3.3 yr. Ninety-one percent of patients reported recurrent symptoms; a mean of 8.8 months after treatment was completed. Sixty-nine percent of patients repeated treatment with the steroid inhaler at least once. CONCLUSIONS: It appears that EE is a chronic remitting disorder that requires more than one topical steroid treatment course.