Economic and survival burden of dysphagia among inpatients in the United States.

The inpatient burden of dysphagia has primarily been evaluated in patients with stroke. It is unclear whether dysphagia, irrespective of cause, is associated with worse clinical outcomes and higher costs compared to inpatients with similar demographic, hospital, and clinical characteristics without dysphagia. The aim of this study is to assess how a dysphagia diagnosis affects length of hospital stay (LOS), costs, discharge disposition, and in-hospital mortality among adult US inpatients. Annual and overall dysphagia prevalence, LOS, hospital charges, inpatient care costs, discharge disposition, and in-hospital mortality were measured using the AHRQ Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (2009-2013). Patients aged 45 years or older with ≤180 days of stay in hospital with and without dysphagia were included. Multivariable survey regression methods with propensity weighting were used to assess associations between dysphagia and different outcomes. Overall, 2.7 of 88 million (3.0%) adult US inpatients had a dysphagia diagnosis (50.2% male, 72.4% white, 74.6% age 65-90 years) and prevalence increased from 408,035 (2.5% of admissions) in 2009 to 656,655 (3.3%) in 2013. After inverse probability of treatment weighting adjustment, mean hospital LOS in patients with dysphagia was 8.8 days (95% CI 8.66-8.90) compared to 5.0 days (95% CI 4.97-5.05) in the non-dysphagia group (P < 0.001). Total inpatient costs were a mean $6,243 higher among those with dysphagia diagnoses ($19,244 vs. 13,001, P < 0.001). Patients with dysphagia were 33.2% more likely to be transferred to post-acute care facility (71.9% vs. 38.7%, P < 0.001) with an adjusted OR of 2.8 (95% CI 2.73-2.81, P < 0.001). Compared to non-cases, adult patients with dysphagia were 1.7 times more likely to die in the hospital (95% CI 1.67-1.74). Dysphagia affects 3.0% of all adult US inpatients (aged 45-90 years) and is associated with a significantly longer hospital length of stay, higher inpatient costs, a higher likelihood of discharge to post-acute care facility, and inpatient mortality when compared to those with similar patient, hospital size, and clinical characteristics without dysphagia. Dysphagia has a substantial health and cost burden on the US healthcare system.

Weight loss in achalasia is determined by its phenotype.

Patients with achalasia present with dysphagia, regurgitation, and varying degrees of weight loss. However, despite it being a disorder of the lower esophageal sphincter with functional obstruction in all patients, it is unclear why certain patients lose significantly more weight compared to others. The aims of this study are to assess demographic, clinical, and manometric characteristics of a large cohort of patients with achalasia to determine potential correlates of weight loss in this population. Patients with diagnosis of achalasia referred to our center between 2009 and 2016 were evaluated. Demographic and physiologic tests between those with and without weight loss were compared. The cohort of patients with initial self-reported weight loss were studied to determine change in weight after intervention (pneumatic dilation or myotomy). The Kruskal-Wallis test was used for comparison of continuous variables between groups and Pearson's χ2 test was used for comparison of categorical variables between groups. 138 patients with achalasia were evaluated. 35 patients were excluded due to lack of manometric data and 3 from lack of documented weight resulting in the study population of 100 patients with achalasia [51% male, median age: 56 years]. Weight loss was reported in 51/100 (51%) patients. BMI was lower in patients who reported weight loss (25 vs. 31, P < 0.001) with a median weight loss of 28 lbs (14-40 lbs). There were no significant differences in age at diagnosis, gender, or symptom presentation (dysphagia, regurgitation, or chest pain) between the groups. However, more patients with type II achalasia (63%) reported weight loss as compared to other sub-types (P = 0.013). 73% of type III achalasia denied having weight loss. Patients who denied weight loss had symptoms for longer duration (24 vs. 12 months, P < 0.001) and had lower mean residual LES pressure (20 vs. 30 mmHg, P = 0.006). Postintervention 42% of patients reported no weight regain despite appropriate therapy for achalasia with median follow-up of 22 months (range: 6-90 months). Type II achalasia patients are most likely and type III achalasia are least likely to have weight loss compared to type I achalasia. Given that no other demographic/physiologic parameters predicted weight loss, the role of underlying inflammatory cascade in achalasia phenotypes deserves special attention.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation.

OBJECTIVE: Patient-reported outcome (PRO) measures are commonly used to capture patient experience with dysphagia and to evaluate treatment effectiveness. Inappropriate application can lead to distorted results in clinical studies. A systematic review of the literature on dysphagia-related PRO measures was performed to (1) identify all currently available measures and (2) to evaluate each for the presence of important measurement properties that would affect their applicability. DESIGN: MEDLINE via the PubMed interface, the Cumulative Index of Nursing and Allied Health Literature, and the Health and Psychosocial Instrument database were searched using relevant vocabulary terms and key terms related to PRO measures and dysphagia. Three independent investigators performed abstract and full text reviews. Each study meeting criteria was evaluated using an 18-item checklist developed a priori that assessed multiple domains: (1) conceptual model, (2) content validity, (3) reliability, (4) construct validity, (6) scoring and interpretation, and (7) burden and presentation. RESULTS: Of 4950 abstracts reviewed, a total of 34 dysphagia-related PRO measures (publication year 1987-2014) met criteria for extraction and analysis. Several PRO measures were of high quality (MADS for achalasia, SWAL-QOL and SSQ for oropharyngeal dysphagia, PROMIS-GI for general dysphagia, EORTC-QLQ-OG25 for esophageal cancer, ROMP-swallowing for Parkinson's Disease, DSQ-EoE for eosinophilic esophagitis, and SOAL for total laryngectomy-related dysphagia). In all, 17 met at least one criterion per domain. Thematic deficiencies in current measures were evident including: (1) direct patient involvement in content development, (2) empirically justified dimensionality, (3) demonstrable responsiveness to change, (4) plan for interpreting missing responses, and (5) literacy level assessment. CONCLUSION: This is the first comprehensive systematic review assessing developmental properties of all available dysphagia-related PRO measures. We identified several instruments with robust measurement properties in multiple diseases including achalasia, oropharyngeal dysphagia, post-surgical dysphagia, esophageal cancer, and dysphagia related to neurological diseases. Findings herein can assist clinicians and researchers in making more informed decisions in selecting the most fundamentally sound PRO measure for a given clinical, research, or quality initiative.

Randomized controlled trial comparing esophageal dilation to no dilation among adults with esophageal eosinophilia and dysphagia.

The role of esophageal dilation in patients with esophageal eosinophilia with dysphagia remains unknown. The practice of dilation is currently based on center preferences and expert opinion. The aim of this study is to determine if, and to what extent, dysphagia improves in response to initial esophageal dilation followed by standard medical therapies. We conducted a randomized, blinded, controlled trial evaluating adult patients with dysphagia and newly diagnosed esophageal eosinophilia from 2008 to 2013. Patients were randomized to dilation or no dilation at time of endoscopy and blinded to dilation status. Endoscopic features were graded as major and minor. Subsequent to randomization and endoscopy, all patients received fluticasone and dexlansoprazole for 2 months. The primary study outcome was reduction in overall dysphagia score, assessed at 30 and 60 days post-intervention. Patients with severe strictures (less than 7-mm esophageal diameter) were excluded from the study. Thirty-one patients were randomized and completed the protocol: 17 randomized to dilation and 14 to no dilation. Both groups were similar with regard to gender, age, eosinophil density, endoscopic score, and baseline dysphagia score. The population exhibited moderate to severe dysphagia and moderate esophageal stricturing at baseline. Overall, there was a significant (P < 0.001) but similar reduction in mean dysphagia score at 30 and 60 days post-randomization compared with baseline in both groups. No significant difference in dysphagia scores between treatment groups after 30 (P = 0.93) or 60 (P = 0.21) days post-intervention was observed. Esophageal dilation did not result in additional improvement in dysphagia score compared with treatment with proton pump inhibitor and fluticasone alone. In patients with symptomatic esophageal eosinophilia without severe stricture, dilation does not appear to be a necessary initial treatment strategy.

Eosinophilic esophagitis: dilate or medicate? A cost analysis model of the choice of initial therapy.

Eosinophilic esophagitis (EoE) is an increasingly recognized clinical entity. The optimal initial treatment strategy in adults with EoE remains controversial. The aim of this study was to employ a decision analysis model to determine the less costly option between the two most commonly employed treatment strategies in EoE. We constructed a model for an index case of a patient with biopsy-proven EoE who continues to be symptomatic despite proton-pump inhibitor therapy. The following treatment strategies were included: (i) swallowed fluticasone inhaler (followed by esophagogastroduodenoscopy [EGD] with dilation if ineffective); and (ii) EGD with dilation (followed by swallowed fluticasone inhaler if ineffective). The time horizon was 1 year. The model focused on cost analysis of initial treatment strategies. The perspective of the healthcare payer was used. Sensitivity analyses were performed to assess the robustness of the model. For every patient whose symptoms improved or resolved with the strategy of fluticasone first followed by EGD, if necessary, it cost an average of $1078. Similarly, it cost an average of $1171 per patient if EGD with dilation was employed first. Sensitivity analyses indicated that initial treatment with fluticasone was the less costly strategy to improve dysphagia symptoms as long as the effectiveness of fluticasone remains at or above 0.62. Swallowed fluticasone inhaler (followed by EGD with dilation if necessary) is the more economical initial strategy when compared with EGD with dilation first.

Symptom association probability does not reliably distinguish functional heartburn from reflux hypersensitivity.

BACKGROUND: Symptom association probability (SAP) is thought to distinguish reflux hypersensitivity from functional disorders. A diagnosis of hypersensitive oesophagus (SAP-positive) indicates that gastro-oesophageal reflux disease (GERD) is the cause of continued symptoms. AIM: To conduct an analysis of pH and symptom criteria that lead to a diagnosis of SAP-positivity METHODS: We calculated SAP for 205 patients with GERD symptoms refractory to proton pump inhibitor (PPI) therapy who underwent endoscopy with wireless pH monitoring from 2007 to 2014. Patients were divided into three groups: pH-negative with no oesophagitis (n = 45), pH-positive with no oesophagitis (n = 130), and patients with oesophagitis (n = 30). We constructed a 2 × 2 table of symptom and reflux event association and quantified the number of 2-minute intervals for each of the 2 × 2 variables that distinguished SAP-positive from SAP-negative. In a separate cohort of 58 patients who had undergone anti-reflux surgery, we evaluated the effects of pre-surgery SAP. RESULTS: The difference in symptom association parameters that led to a diagnosis of an SAP-positive was small (2.98% in oesophagitis-positive; 1.56% in oesophagitis-negative/pH-positive; 0.48% in oesophagitis-negative/pH-negative). In the pH-negative/oesophagitis-negative group, a difference of 0.48% led to a diagnosis of hypersensitivity. There was significant variability in SAP values between day 1 and day 2 of pH testing in all groups, with the greatest in the oesophagitis-positive group, despite objective evidence for reflux (27% in oesophagitis-positive, 19% pH-positive/oesophagitis-negative, and 7% in pH-negative/oesophagitis-negative). Pre-surgery SAP was not associated with response to anti-reflux surgery. CONCLUSION: In PPI-refractory GERD, SAP cannot accurately distinguish reflux hypersensitivity from functional oesophageal symptoms.

Laryngeal disorders in patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common medical condition affecting approximately 35-40% of the adult population in the western world. Chronic laryngeal signs and symptoms associated with GERD are often referred to as reflux laryngitis or laryngopharyngeal reflux (LPR). It is estimated that up to 15% of all visits to the otolaryngology offices are because of manifestations of LPR. Injury may occur as a result of one or chronic reflux of gastroduodenal contents directly injuring the laryngeal mucosa. Since less amount of acid is required to make the injury to the larynx as compared to injury to esophagus; it is believed that intermittent exposure to small amount of gastric content can result in laryngitis. The most common presenting symptoms of LPR include hoarseness, sore throat, throat clearing, and chronic cough. The diagnosis of LPR is usually made on the basis of presenting symptoms and associated laryngeal signs including laryngeal edema and erythema. Current recommendation for management of this group of patients is empiric therapy with twice daily proton-pump inhibitors for 2 to 4 months. In majority of those who are unresponsive to such therapy other causes of laryngeal irritation is considered. Surgical fundoplication is most effective in those who are responsive to acid suppressive therapy.

Does my patient still have reflux when ppi therapy does not work?

Gastroesophageal reflux disease (GERD) is a common condition around the world. The management of this disease is less than satisfying given complexity of patient presentation and suboptimal diagnostic testing when employed for those poorly responsive to acid suppressive therapy. In this mini review, we discuss some new strategies employed for patients with suspected GERD to better understand disease pathophysiology. We compare the strategies and outline a clinically relevant approach in this difficult group of patients.

Review article: the role of pH monitoring in extraoesophageal gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease is associated with several extraoesophageal disease states including laryngitis, asthma, chronic cough and non-cardiac chest pain. Currently, the exact role reflux of gastric contents play in the pathogenesis of extraoesophageal symptoms remain controversial. Twenty-four hours pH monitoring is often considered the 'gold standard' in the diagnosis of gastro-oesophageal reflux disease and is increasingly utilized in patients with extraoesophageal symptoms. The use of this test is aimed at improving the association between patients' extraoesophageal symptoms and oesophageal or hypopharyngeal acid reflux events. However, the clinical utility of pH monitoring in this patient population remains controversial. Important clinical questions in this area include: does the presence of abnormal oesophageal acid reflux suggest a causal association between patients' extraoesophageal symptoms and gastro-oesophageal reflux disease? Conversely, does the absence of abnormal acid exposure in the oesophagus suggest lack of such an association? Should the test be performed on or off therapy and does it matter? In this study, the role of pH monitoring in laryngitis, asthma, chronic cough and non-cardiac chest pain is examined and answers to the above questions are addressed based on current data.

Dietary carbohydrate intake, insulin resistance and gastro-oesophageal reflux disease: a pilot study in European- and African-American obese women.

BACKGROUND: Although obesity rates are higher in African-American than European-American women, gastro-oesophageal reflux disease (GERD) and its comorbidities are more prevalent in European-American women. A common denominator for increased adiposity, and consequent insulin resistance, is excess dietary macronutrient intake - which may promote greater prevalence and severity of GERD in women. AIM: To investigate whether GERD is more robustly associated with dietary carbohydrate intake, particularly dietary simple carbohydrate intake, and insulin resistance in European-American women. METHODS: About 144 obese women were assessed at baseline and 16 weeks after consuming a high-fat/low-carbohydrate diet. GERD diagnosis and medication usage was confirmed in medical records with symptoms and medications assessed weekly. RESULTS: About 33.3% (N = 33) of European-American and 20.0% (N = 9) of African-American women had GERD at baseline. Total carbohydrate (r = 0.34, P < 0.001), sugars (r = 0.30, P = 0.005), glycaemic load (r = 0.34, P = 0.001) and HOMAIR (r = 0.30, P = 0.004) were associated with GERD, but only in European-American women. In response to high-fat/low-carbohydrate diet, reduced intake of sugars was associated with reduced insulin resistance. By the end of diet week 10, all GERD symptoms and medication usage had resolved in all women. CONCLUSIONS: GERD symptoms and medication usage was more prevalent in European-American women, for whom the relationships between dietary carbohydrate intake, insulin resistance and GERD were most significant. Nevertheless, high-fat/low-carbohydrate diet benefited all women with regard to reducing GERD symptoms and frequency of medication use.

Duodenogastroesophageal reflux and methods to monitor nonacidic reflux.

The role of duodenogastroesophageal reflux (DGER), once erroneously termed "bile reflux," in causing esophageal mucosal damage has been an area of interest in both animal and human studies. However, because of the lack of appropriate techniques to accurately measure DGER, extrapolation of findings from animal studies to humans has been difficult to make. The recent advent of the Bilitec system (Metronics Instruments, Minneapolis, MN), an ambulatory bilirubin monitoring device, is increasing our knowledge of the specific role of DGER in esophageal diseases. Studies suggest that DGER without acid reflux may result in symptoms, but unless acid reflux is present simultaneously, it does not cause esophagitis. Therefore, therapies should aim at reducing both DGER and acid reflux. Studies show that this may be accomplished by antireflux surgery or the use of proton pump inhibitors, which by reducing gastric volume, decrease the damaging potential of both acid and DGER.

A conformationally defined 6-s-trans-retinoic acid isomer: synthesis, chemopreventive activity, and toxicity.

A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-configuration for the intermediate aldehyde. A Horners-Emmons condensation with this aldehyde then produced retinoic acid analogs with both 9Z- and 9Z,13Z-configurations. An I2-catalyzed isomerization of the intermediate 9Z-aldehyde yielded the all-E-aldehyde, which was olefinated as above to yield the (all-E)- and (13Z)-retinoic acid analogs of 1. Each configurational isomer of 1 was evaluated for its ability to inhibit the binding of retinoic acid to CRABP (chick skin) and to inhibit the chemical induction of ornithine decarboxylase in mouse skin. In each assay (all-E)-1 was the most active isomer, and this activity was comparable to or better than that for (all-E)-retinoic acid. (all-E)-1 and (13Z)-1 were both shown to be equally effective as (13Z)-retinoic acid in suppressing the proliferation of human sebaceous cells in vitro. (all-E)-1 was further evaluated for its ability to prevent the induction of mouse skin papillomas and to induce signs of vitamin A toxicity in mice. The cancer chemopreventive activity of (all-E)-1 was comparable to that of (all-E)-retinoic acid, and the toxicity was comparable to or slightly better than that of the natural vitamin.

Conformationally defined 6-s-trans-retinoic acid analogs. 3. Structure-activity relationships for nuclear receptor binding, transcriptional activity, and cancer chemopreventive activity.

We recently demonstrated that conformationally defined 6-s-trans-retinoic acid (RA) analogs were effective in the prevention of skin papillomas (Vaezi et al. J. Med. Chem. 1994, 37, 4499-4507) and selective agonists for nuclear receptor binding and activation (Alam et al. J. Med. Chem. 1995, 38, 2302-2310). In order to probe important structure-activity relationships, we evaluated a homologous series of four 6-s-trans-retinoids that are 8-(2'-cyclohexen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acids with different substituents at 2' (R2) and 3' (R1) positions on the cyclohexene ring. UAB1 (R1 = R2 = H), UAB4 (R1 = R2 = Me), UAB7 (R1 = Me, R2 = iPr), and UAB8 (R1 = Et, R2 = iPr) contain alkyl R groups that mimic, to different extents, portions of the trimethylcyclohexenyl ring of RA. Both 9Z- and all-E-isomers of these retinoids were evaluated in binding assays for cellular retinoic acid-binding proteins (CRABP-I and CRABP-II), a nuclear retinoic acid receptor (RAR alpha), and a nuclear retinoid X receptor (RXR alpha). The all-E-isomers of UAB retinoids bound tightly to CRABPs and RAR alpha, the binding affinity of the all-E-isomer increased systematically from UAB1 to UAB8, and binding for the latter was comparable to that of all-E-RA. In contrast to RA, the (9Z)-UAB retinoids were at least 200-fold less active than the all-E-isomers in binding to RAR alpha. The (9Z)-UAB isomers exhibited increasingly stronger binding to RXR alpha, and (9Z)-UAB8 was nearly as effective as (9Z)-RA in binding affinity. The retinoids were also evaluated in gene expression assays mediated by RAR alpha and RXR alpha homodimers or RAR alpha/RXR alpha heterodimers. Consistent with the binding affinities, the (all-E)-UAB retinoids activated gene transciption mediated by RAR alpha homodimers or RAR alpha/RXR alpha heterodimers, while the (9Z)-UAB isomers activated only the RXR alpha homodimer-mediated transcription. The all-E- and 9Z-isomers of the UAB retinoids were further evaluated for their capacity to prevent the induction of mouse skin papillomas. When compared to RA, only the (all-E)-UAB retinoids containing bulky R1 and R2 groups were effective in this chemoprevention assay. (9Z)-RA displayed equal capacity as RA to prevent papillomas, while the 9Z-isomers of the UAB retinoids were much less effective. Taken together, these studies demonstrate that the cyclohexenyl ring substituents of 6-s-trans-UAB retinoids are important for their biological activities and that the chemopreventive effect of the all-E-isomers of these retinoids correlates well with their capacity to bind to RARs and activate RAR/RXR-mediated transcription.

Ambulatory gastric pH monitoring: proper probe placement and normal values.

BACKGROUND: Gastric acid production may persist while patients are treated with proton pump inhibitors. Twenty-four-hour intragastric pH monitoring is being used to identify gastric acid in the stomach while on medical therapy. AIM: To identify the optimal region of the stomach to demonstrate the presence of gastric acid. METHOD: Probe locations confirmed with fluoroscopy after placement and prior to removal. In experiment 1, five volunteers underwent simultaneous, 24-h gastro-oesophageal pH monitoring with the pH sensors located in the gastric antrum, body, fundus and distal oesophagus. In experiment 2, five volunteers underwent simultaneous 24-h pH monitoring with sensors located side by side in the gastric fundus assessing the reproducibility of gastric pH in this region. In experiment 3, 35 volunteers underwent 24-h pH monitoring with pH sensors located in the distal oesophagus and gastric fundus. The mean percentage time for which pH < 4 was calculated for total, upright, and supine time periods. RESULTS: pH profiles for the gastric fundus and body are similar-the mean percentage total time for which pH < 4 was 92.2% and 90.1%, respectively (P=N.S.). These values are significantly different from the antrum; pH < 4=54.6% (P < 0.01). pH values from the gastric fundus are highly reproducible (linear regression P= 0.004, r(2)=0.96). The normal values (mean +/- 95th percentile) for percentage time gastric pH < 4 in the fundus were: total 95.6 +/- 1.5%, upright 94.8 +/- 1.8%, and supine 96.5 +/- 2.3%. CONCLUSION: The fundus is the optimal location to evaluate the presence of gastric acid; pH values are highly reproducible in this area. Normal values for percentage time gastric pH < 4 for a healthy population are now defined.

Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach.

The histological distinction between intestinal metaplasia involving the distal esophagus (Barrett's esophagus [BE]) and intestinal metaplasia of the stomach has important clinical implications and can be difficult even with the use of histochemical mucin stains. Cytokeratin (CK) 7 and 20 are cytoplasmic structural proteins that show restricted expression in normal and malignant epithelia of the gastrointestinal tract. The aim of this study was to determine the use of CK7 and 20 expression in the histological distinction of BE from gastric intestinal metaplasia. CK7 and 20 immunostaining was performed on randomly selected surgical resection (n = 31) and biopsy specimens (n = 34) from patients with long-segment BE and gastric resection specimens (n = 11) and gastric cardia biopsy specimens (n = 13) in patients with histological evidence of intestinal metaplasia. A unique pattern of immunoreactivity designated the Barrett's CK7/20 pattern showed superficial CK20 staining and strong CK7 staining of both superficial and deep glands in 29 of 31 (94%) esophageal resection specimens and 34 of 34 (100%) esophageal biopsy specimens form patients with long-segment BE. A Barrett's CK7/20 pattern was not observed in gastric cardia biopsy specimens (n = 13) or gastric resection specimens (n = 11) in patients with histological evidence of intestinal metaplasia. The sensitivity, specificity, and positive predictive value of a Barrett's CK7/20 pattern for a diagnosis of long-segment BE was 97%, 100%, and 100%, respectively. CK7 and 20 reactivity patterns can reliably identify the location of intestinal metaplasia in the esophagus and stomach using histological material from both routine endoscopic biopsy and surgical resection specimens.

Synergism of acid and duodenogastroesophageal reflux in complicated Barrett's esophagus.

BACKGROUND: The role of acid and duodenogastroesophageal reflux (DGER) in the development of complications in Barrett's esophagus is controversial. We characterized the esophageal reflux constituents in patients with and without complications of Barrett's esophagus. METHODS: Using a new fiber-optic system we studied 12 normal subjects (six male; mean age, 46 years) and 20 patients with Barrett's esophagus (17 male; mean age, 58 years), nine with uncomplicated (seven male; mean age, 55 years) and 11 with complicated Barrett's esophagus (seven with stricture, two with ulcer, and two with dysplasia; 10 male; mean age, 61 years). Fasting gastric bile acid concentrations were measured. Twenty-four-hour ambulatory acid and bilirubin measurements were obtained with the fiber-optic system by using a glass electrode and fiber-optic sensor. The data were then analyzed for percent total time pH < 4 and > 7 and bilirubin absorbance > 0.14%. RESULTS: Percent times pH < 4, bilirubin absorbance > 0.14%, and fasting gastric bile acid concentrations were significantly greater in patients with complicated Barrett's esophagus compared with patients with uncomplicated Barrett's esophagus with both being higher than the controls. Acid reflux paralleled bile reflux in the two Barrett's esophagus groups (r = 0.44, p < 0.05), but percent time pH > 7 did not differentiate between the two groups. CONCLUSIONS: (1) Patients with complicated Barrett's esophagus reflux significantly greater amounts of both acid and duodenal contents than patients with uncomplicated Barrett's esophagus. (2) Complications in Barrett's esophagus may be due to synergism between acid and bile rather than either constituent alone.

Quantitative methods to determine efficacy of treatment in achalasia.

Determining success after achalasia therapy is an important aspect of treating this disease. Esophageal manometry, scintigraphy, and barium esophagram are the most commonly employed techniques. Recent data suggest that barium esophagram may be most practical and informative compared to manometry and scintigraphy in predicting treatment success in achalasia patients after therapy.

New techniques in measuring nonacidic esophageal reflux.

New techniques in esophageal monitoring are allowing for better differentiation in the role of different gastric refluxates in esophageal mucosal damage and patient symptoms. The Bilitec 2001 (Synectics, Stockholm, Sweden) is a portable spectrophotometer that measures bilirubin as a surrogate marker for bile reflux and multichannel intraluminal impedance (MII) (Sandhill Scientific Inc, Highlands Ranch, CO) is a new technique allowing measurement of esophageal volume refluxate. Both techniques assess the role of nonacidic esophageal reflux. Despite their novel approach in assessing nonacid reflux, both methods have limitations. Future studies in this area, however, will prove beneficial in identifying their role in diagnosis and management of patients with suspected nonacid reflux disease.

Importance of duodeno-gastro-esophageal reflux in the medical outpatient practice.

BACKGROUND/AIMS: The role of acid and duodeno-gastro-esophageal reflux (DGER), also termed bile reflux, in esophageal mucosal injury is controversial. Several recent developments, especially availability of the recent bilirubin monitoring device (Bilitec), have resulted in clarifications in this area. In order to better understand the role of acid and DGER in esophageal mucosal injury, we summarized the recent publications in this area. METHODOLOGY: Review of published medical literature (MEDLINE) on the clinical consequence of esophageal exposure to gastric acid or DGER. RESULTS: Recent data suggest that esophageal pH monitoring and pH > 7 is a poor marker for reflux of duodenal contents into the esophagus. DGER in non-acidic environments (i.e., partial gastrectomy patients) may cause symptoms but does not cause esophageal mucosal injury. Acid and duodenal contents usually reflux into the esophagus simultaneously, and may be contributing to the development of Barrett's metaplasia and possibly adenocarcinoma. Proton pump inhibitors decrease acid and DGER by reducing intragastric volume available for reflux and raising intragastric pH. The promotility agent cisapride decreases DGER by increasing LES pressure and improving gastric emptying. CONCLUSIONS: 1) The term "alkaline reflux" is a misnormer and should no longer be used in referring to reflux of duodenal contents. 2) Bilitec is the method of choice in detecting DGER and should always be used simultaneously with esophageal pH-monitoring for acid reflux. 3) DGER alone is not injurious to esophageal mucosa, but can result in significant esophageal mucosal injury when combined with acid reflux. 4) Therefore, controlling esophageal exposure to acid reflux by using proton pump inhibitors also eliminates the potentially damaging effect of DGER.