Categorization of patients with reflux symptoms referred for pH and impedance testing while off therapy.

BACKGROUND & AIMS: Patients with suspected gastroesophageal reflux disease (GERD) often are treated empirically with proton pump inhibitors (PPIs). Patients whose symptoms are not reduced during the PPI trial are referred for further tests. We investigated whether patients referred for the evaluation of reflux symptoms had GERD. We also aimed to categorize patients with a poor response to PPIs into groups with hypersensitive esophagus or functional heartburn. METHODS: We performed a retrospective study, searching a clinical database of patients referred for GERD testing from 2006 through 2011. We collected data on all patients who underwent upper endoscopy, esophageal manometry, and 24-hour pH-impedance monitoring, and were off PPIs for at least 1 week. Evidence of GERD was determined by an abnormal upper endoscopy or 24-hour pH-impedance monitoring. Further categorization was determined by impedance results and the symptom association probability index. RESULTS: We identified 221 patients (mean age, 47.6 ± 13.3 y; 56% male; 61% Caucasians); 97% previously had been prescribed PPIs, before they were tested. The patients had erosive esophagitis (n = 21; 10%), nonerosive reflux disease with increased pH (n = 61; 27%), nonerosive reflux disease with abnormal impedance (n = 18; 8%), hypersensitive esophagus (n = 30; 14%), functional heartburn (n = 18; 8%), functional disorders other than heartburn (n = 30; 14%), and undetermined disorders (n = 43; 19%). CONCLUSIONS: In a retrospective analysis of 221 patients, roughly half of the patients referred for testing did not have evidence of GERD. Further categorization of patients can help guide diagnosis and management.

A randomized controlled study comparing room air with carbon dioxide for abdominal pain, distention, and recovery time in patients undergoing colonoscopy.

Colonoscopy remains the gold standard for colorectal cancer screening. Many barriers to the procedure exist including the possibility of abdominal discomfort that may occur with insufflation. Carbon dioxide (CO2), which is rapidly absorbed in the blood stream, is an alternate method used to distend the lumen during colonoscopy. The goal of this study was to compare patient discomfort, abdominal girth, and recovery time in 2 groups of patients randomized to CO2 versus room air insufflation during colonoscopy. Using a Wong-Baker score, we found statistical difference in postprocedural discomfort levels (CO2 Group: 1.15 ± 2.0 vs. room air: 0.41 ± 0.31, p = .015) and a significantly greater increase in abdominal girth over CO2 immediately postprocedure (room air: 1.06 ± 1.29 inches vs. CO2: 0.56 ± 0.73 inches, p = .054) girth immediately postprocedure; however, recovery time was similar between the 2 study arms (CO2: 9.1 ± 16.2 minutes vs. room air: 10.2 ± 18.6 minutes, p = .713). Further studies are needed to determine whether CO2 is cost-effective and improves patient satisfaction with colonoscopy.

Endotherapy for and tailored approaches to treating GERD, and refractory GERD.

This paper presents commentaries on how endoluminal antireflux procedures compare to laparoscopic fundoplication; new endoscopic procedures being studied to treat refractory gastroesophageal reflux disease (GERD); the new Stretta; the relationship between obesity and proton pump inhibitor (PPI) resistance; data concerning acid hypersensitivity and sensory receptors (vallinoid, TRPV1) causing refractory GERD; whether microscopic esophagitis is relevant in determining symptoms of non-erosive reflux disease (NERD); how concomitant functional gastrointestinal disorders affect the PPI response in NERD; the evidence that a functional esophagus is associated with inflammatory bowel syndrome (IBS); the role of GABA agonists in the treatment of refractory GERD; the role of biofeedback and antidepressants in refractory GERD; and endoluminal fundoplication using the EsophyX device.

The dose of omeprazole required to achieve adequate intraesophageal acid suppression in patients with gastroesophageal junction specialized intestinal metaplasia and Barrett's esophagus.

BACKGROUND: The mainstay of medical therapy for Barrett's esophagus is normalization of esophageal acid exposure with proton pump inhibitors (PPIs). However, the optimal dose and whether once daily or twice daily is required for acid suppression is unknown. AIM: The purpose of this study was to assess whether adequate intra-esophageal acid suppression could be achieved with once daily versus twice daily omeprazole in patients with gastroesophageal specialized intestinal metaplasia (GEJSIM), short-segment (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS: Patients with GEJSIM and Barrett's esophagus underwent upper endoscopy with 48-h wireless pH capsule while on once daily 20 mg omeprazole for at least 1 week. If intra-esophageal acid was not adequately controlled, defined as pH value <4 for greater than 4.2 % of the time during the second 24-h period, omeprazole was increased to twice daily for 1 week and upper endoscopy with wireless pH capsule was repeated. RESULTS: A total of 36 patients completed the study (10 patients had GEJSIM, 16 patients had SSBE, and 10 patients had LSBE). Normalization of intraesophageal pH was achieved in 28 patients (78 %) with once daily PPI and eight patients required twice daily PPI. There was no significant difference between the three groups in the proportion of patients requiring high dose PPI (GEJSIM 10 %, SSBE 25 %, LSBE 30 %, p = 0.526). CONCLUSIONS: The majority of patients with Barrett's esophagus were controlled with once daily low dose PPI and only a minority required twice daily dosing, regardless of the length of Barrett's mucosa.

Randomized controlled trial comparing aerosolized swallowed fluticasone to esomeprazole for esophageal eosinophilia.

OBJECTIVES: Patients with clinical symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa are suspected to have eosinophilic esophagitis (EoE). Topical steroids are often used as first-line therapy for EoE, although some patients respond clinically to proton pump inhibitors (PPIs). The purpose of this study was to compare the histological and clinical response of patients with esophageal eosinophilia treated with aerosolized swallowed fluticasone propionate vs. esomeprazole. METHODS: This prospective single-blinded randomized controlled trial enrolled newly diagnosed patients with suspected EoE, defined as having clinical symptoms related to esophageal dysfunction with at least 15 eosinophils/high power field (hpf). Patients underwent 24-h pH/impedance monitoring to establish gastroesophageal reflux disease (GERD). Patients were stratified by the presence of GERD and randomized to receive fluticasone 440 mcg twice daily or esomeprazole 40 mg once daily for 8 weeks followed by repeat endoscopy with biopsies. The primary outcome was histological response of esophageal eosinophilia, defined as <7 eosinophils/hpf. Secondary outcomes included clinical change in symptoms using the validated Mayo dysphagia questionnaire (MDQ) and interval change in endoscopic findings following treatment. RESULTS: Forty-two patients (90% male, 81% white, mean age 38 ± 10 years) were randomized into fluticasone (n = 21) and esomeprazole (n = 21) treatment arms. In all, 19% (8/42) of patients had coexisting GERD and were equally stratified into each arm (n = 4). Overall, there was no significant difference in resolution of esophageal eosinophilia between fluticasone and esomeprazole (19 vs. 33%, P = 0.484). In patients with established GERD, resolution of esophageal eosinophilia was noted in 0% (0/4) of the fluticasone group compared with 100% (4/4) of the esomeprazole group (P = 0.029). In GERD-negative patients, there was no significant difference in resolution of esophageal eosinophilia between treatment arms with fluticasone and esomeprazole (24 vs.18%, P = 1.00). The MDQ score significantly decreased after treatment with esomeprazole (19 ± 21 vs. 1.4 ± 4.5, P<0.001), but not with fluticasone (17 ± 18 vs. 12 ± 16, P = 0.162). Improvement in endoscopic findings and other histological markers were similar between treatment groups. CONCLUSIONS: Fluticasone and esomeprazole provide a similar histological response for esophageal eosinophilia. With regard to clinical response, esomeprazole was superior to fluticasone, particularly in patients with established GERD.

Barrett's esophagus: endoscopic diagnosis.

This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes.

Barrett's esophagus: proton pump inhibitors and chemoprevention II.

The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs.

Differential diagnosis of upper gastrointestinal bleeding proximal to the ligament of Trietz.

Upper gastrointestinal bleeding (UGIB) is an important medical problem for patients and the medical system. The causes of UGIB are varied and their accurate identification guides appropriate management. The major cause of UGIB is peptic ulcer disease, for which Helicobacter pylori and nonsteroidal antiinflammatory drug use are major risk factors. Lesser causes include Dieulafoy lesion, gastric antral vascular ectasia, hemobilia, aortoenteric fistulas, and upper gastrointestinal tumors. Awareness of causes and management of UGIB should allow physicians to treat their patients more effectively.

Esophageal motor disorders in adults with eosinophilic esophagitis.

BACKGROUND: An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. AIMS: The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. METHODS: A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (<30 mmHg) or non-propagating contractions. Ineffective esophageal motility (IEM) was categorized as mild (30-40% ineffective swallows), moderate (50-60% ineffective swallows), and severe (≥70% ineffective swallows). Dysphagia was graded on a 0-3 scale for frequency and severity. RESULTS: Seventy-five tracings from EoE patients were reviewed (85% male, mean age 41 ± 12 years). IEM was identified in 25 patients and categorized as mild (n = 13), moderate (n = 6), and severe (n = 6). Nutcracker esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). CONCLUSIONS: In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

Current approach to the treatment of achalasia.

Achalasia is a primary esophageal motility disorder characterized by aperistalsis and incomplete or absent relaxation of the lower esophageal sphincter (LES). The cause of the disease remains elusive and there is no intervention that improves the esophageal body function. Currently, treatment options focus on palliation of symptoms by reducing the LES pressure. The most effective and well-tolerated treatments continue to be the laparoscopic Heller myotomy and endoscopic pneumatic dilation; however, newer techniques (eg, peroral endoscopic myotomy and self-expanding metal stents) show promise. Botulinum toxin and pharmacologic therapy are reserved for those who are unable to undergo more effective therapies. Treatment options should be tailored to the patient, using current predictors of outcome such as the patient's age and post-treatment LES pressures. The aim of this article is to highlight current literature and provide an up-to-date approach to the treatment of achalasia.

Extracolonic findings on CT colonography increases yield of colorectal cancer screening.

OBJECTIVE: The purpose of this study is to evaluate the impact of extracolonic findings when screening is undertaken by CT colonography (CTC). MATERIALS AND METHODS: We performed a retrospective cohort study of patients completing a screening CTC from August 2003 to June 2006 at Walter Reed Army Medical Center. Extracolonic findings were categorized using a CTC reporting and data system that classifies findings as highly significant, likely significant, and insignificant. All final diagnoses, surgeries, malignancies, and costs of diagnostic radiology procedures were calculated for each category. RESULTS: Of 2,277 patients (mean +/- SD age, 59 +/- 11 years; 60% white; 56% male) undergoing CTC, extracolonic findings were identified in 1,037 (46%) patients, with 787 (34.5%) insignificant and 240 (11.0%) significant findings. Evaluation of significant findings generated 280 radiology procedures and 19 surgeries over a mean follow-up time of 19 +/- 10 months. The total cost of the radiology studies was $113,179; the studies added approximately $50 extra per patient. Seven high-risk lesions were identified (six extracolonic malignancies and one large aortic aneurysm) in patients with significant findings. CTC also identified six intracolonic malignancies and three adenomas with high-grade dysplasia. When considering extracolonic findings, CTC increased the odds of identifying high-risk lesions by 78% (nine intracolonic lesions vs 16 intracolonic plus extracolonic lesions; p = 0.0156). Of the 16 intracolonic and extracolonic high-risk lesions, 11 (69%) underwent curative resection, and 5 of 11 (44.4%) were extracolonic. CONCLUSION: CTC increased the odds of identifying high-risk lesions by 78%. CTC should be considered as an alternative to optical colonoscopy for colorectal cancer screening or as a onetime procedure to identify significant treatable intracolonic and extracolonic lesions.

Chronic proton pump inhibitor therapy associated with increased development of fundic gland polyps.

BACKGROUND: Fundic gland polyps (FGP) have been implicated with long-term proton pump inhibitor (PPI) use. AIMS: We attempted to investigate the impact of length and dosage of PPI therapy on the development of FGP. METHODS: A retrospective cohort study of all patients who had gastric polyps removed during elective upper endoscopy between March and September 2007 as part of a prior prospective study protocol was carried out. FGP were determined histologically. Prior to endoscopy, all patients completed a questionnaire regarding PPI use and length of therapy (no PPI use, 1-48 months, >48 months). The dosage of PPI was obtained via a thorough chart review of electronic medical records. RESULTS: Three hundred and eighty-five patients completed upper endoscopy and a questionnaire reporting PPI use (252 [65.4%] patients on PPI). On endoscopy, 55 patients had polyps, with the majority (43/55, 78%) being FGP, resulting in an overall prevalence of 11.1% (43/385). On univariate analysis, FGP were associated with Caucasian race (15 vs. 6%; P=0.009) and chronic PPI therapy (>48 months) (31.9 vs. 7.5%, P<0.001). There was a significant linear-by-linear association between PPI dosage and FGP prevalence (no PPI use, 7.5%; once daily, 10.8%; twice daily 17.4%, P=0.026). On logistic regression, the only independent predictor of FGP was duration of PPI use >48 months (P=0.001, odds ratio [OR] 4.7 [2.0-12.9]). CONCLUSIONS: The only independent predictor of FGP development in our study was duration of PPI therapy greater than 48 months. Increased dosage of therapy did not significantly impact the development of FGP.

Eosinophilic esophagitis.

Eosinophilic esophagitis is a chronic inflammatory disorder characterized by dense eosinophilic infiltration of the esophageal mucosa. The pathogenesis is incompletely understood and food allergies and aeroallergens have been implicated. The most common clinical presentation in adults is dysphagia to solids. Its associated endoscopic findings are distinct and include concentric rings and longitudinal furrows, although endoscopy may be unremarkable in a minority of patients. A number of management strategies exist; however, data are limited in adults, and only a few are based on randomized controlled trials. Management options include dietary modifications, pharmacological therapy, and endoscopic dilation.

Where are you and how do we find you? The dilemma of identifying Barrett's epithelium before adenocarcinoma of the esophagus.

The incidence of esophageal adenocarcinoma in white males has been increasing steadily over the past decade. However, attempts to identify the precursor lesion, intestinal metaplasia of the esophagus, or early in-situ cancers have been dismal, with no increase in the diagnosis of early cancers over 9 years of follow-up, as noted in the study by Cooper et al. Important predictors of survival,such as a previous diagnosis of gastroesophageal reflux disease, endoscopy, and the diagnosis of intestinal metaplasia, continue to represent a minority of patients who present with esophageal adenocarcinoma. A discussion on the possible pathophysiology, and reasons for the poor diagnostic yields in spite of performing more endoscopies, are presented. It may be that most patients are relatively asymptomatic, or have very distal, endoscopically imperceptible intestinal metaplasia. Over time, factors that encourage localized, distal esophageal reflux may be the insidious culprit that leads to intestinal metaplasia.

Prevalence of eosinophilic esophagitis in an adult population undergoing upper endoscopy: a prospective study.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus. The purpose of this prospective study was to determine the prevalence and clinical predictors of EoE in patients undergoing elective upper endoscopy. METHODS: We enrolled 400 consecutive adults (median age, 50 years; range, 19-92 years) who underwent routine upper endoscopy from March to September 2007 at a tertiary care military hospital. All patients completed a symptom questionnaire. All endoscopic findings were noted. Eight biopsies were obtained from proximal and distal esophagus and were reviewed by a blinded gastrointestinal pathologist. Patients had EoE if > or =20 eosinophils/high-power field were present. RESULTS: The prevalence of EoE in this cohort was 6.5% (25/385; 95% confidence interval, 4.3%-9.4%). Compared with EoE negative patients, EoE positive patients were more likely to be male (80.0% vs 48.1%, P = .003), younger than 50 years (72.0% vs 48.9%, P = .037), and have asthma (32.0% vs 10.8%, P = .006), a food impaction (32.0% vs 8.9%, P = .002), dysphagia (64.0% vs 38.1%, P = .018), and classic endoscopic findings (rings, furrows, plaques, or strictures) of EoE (all P < .01). Logistic regression identified asthma (odds ratio [OR], 4.48), male gender (OR, 4.23), and esophageal rings (OR, 13.1) as independent predictors of EoE. The presence of classic endoscopic findings of EoE had a sensitivity of 72% (54%-88%), specificity of 89% (87%-90%), and negative predictive value of 98% (95.6%-99.1%). CONCLUSIONS: The prevalence of EoE in an outpatient population undergoing upper endoscopy was 6.5%. The characteristic findings of EoE patients included male gender, history of asthma, and the presence of classic findings of EoE on endoscopy, which is the strongest predictor of this disease process.

A randomized comparison of methylene blue-directed biopsy versus conventional four-quadrant biopsy for the detection of intestinal metaplasia and dysplasia in patients with long-segment Barrett's esophagus.

OBJECTIVES: Methylene blue (MB) selectively stains specialized intestinal metaplasia (SIM) and may assist in surveying a columnar-lined esophagus for Barrett's esophagus associated dysplasia. METHODS: This is a prospective, randomized crossover study comparing 4-quadrant random biopsies (4QB) versus MB-directed biopsies for the detection of SIM and dysplasia in 48 patients with long segment Barrett's esophagus (LSBE). Patients randomly underwent two endoscopies over a 4-wk time period with either 4QB or MB-directed biopsies as their first or second exam. Our aim was to correlate stain intensity with histology. RESULTS: The sensitivity of MB for SIM and dysplasia was 75.2% and 83.1%, respectively. The yield of 4QB for identifying nondysplasia SIM was 57.6% (523/917) and for dysplasia was 12% (111/917). Dark staining was significantly associated with histologic grade (P < 0.007). The final diagnosis was correct in 43 (90%) patients using MB and in 45 (94%) using 4QB. The 4QB technique missed dysplasia in 3 of 21 patients while MB biopsies missed dysplasia in 5 of 21 patients. The discordance between the two techniques was not significant (P= 0.727, McNemar's test). The mean number of biopsies taken during 4QB was 18.92 +/- 6.36 and with MB was 9.23 +/- 2.89 (P < 0.001). CONCLUSION: MB requires significantly fewer biopsies than 4QB to evaluate for SIM and dysplasia. Dark staining correlates more with HGD than LGD in our experience. While MB is not more accurate than 4QB, MB may help to define areas to target for biopsy during surveillance endoscopy in patients with LSBE.