White Paper AGA: Drug Development for Eosinophilic Esophagitis

Since first characterized in 2 small case series in the early 1990s, eosinophilic esophagitis (EoE) has emerged as a commonly identified cause of esophageal symptoms in children and adults. Although several highly effectively dietary, pharmacologic, and endoscopic therapies have been reported, none is currently approved by either the US Food and Drug Administration (FDA) or European regulatory authorities. Evolving diagnostic criteria have challenged drug development, in particular the recognition of complex interactions with the most prevalent esophageal disorder, gastroesophageal reflux disease (GERD). Heterogeneity in the clinical presentations of affected children and adults has created difficulties with uniform inclusion criteria and the development of disease-specific, patient-reported outcome (PRO) instruments. Furthermore, controversies regarding the appropriate therapeutic endpoints of EoE have impeded the design of clinical trials. Despite these obstacles, collaborative efforts by investigators, industry, the FDA, and patient advocacy groups have resulted in substantial progress in drug development in EoE over the past 2 decades. The purpose of this article is to summarize discussions on EoE based on the 2016 Drug Development Conference sponsored by the Center for Diagnostics and Therapeutics of the American Gastroenterological Association

Dietary antioxidant intake and the risk of developing Barrett’s oesophagus and oesophageal adenocarcinoma

Background: We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC). Methods: A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence. Results: A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71–0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37–0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51–0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51–0.96; P = 0.03). Conclusions: Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis

Gender effect on clinical features of achalasia: a prospective study

BACKGROUND: Achalasia is a well-characterized esophageal motor disorder but the rarity of the disease limits performing large studies on its demographic and clinical features. METHODS: Prospectively, 213 achalasia patients (110 men and 103 women) were enrolled in the study. The diagnosis established by clinical, radiographic, and endoscopic as well as manometry criteria. All patients underwent a pre-designed clinical evaluation before and within 6 months after the treatment. RESULTS: Solid dysphagia was the most common clinical symptom in men and women. Chest pain was the only symptom which was significantly different between two groups and was more complained by women than men (70.9% vs. 54.5% P value= 0.03). Although the occurrence of chest pain significantly reduced after treatment in both groups (P < 0.001), it was still higher among women (32% vs. 20.9% P value= 0.04). In both sexes, chest pain did not relate to the symptom duration, LES pressure and type of treatment patients received. Also no significant relation was found between chest pain and other symptoms expressed by men and women before and after treatment. Chest pain was less frequently reported by patients over 56 yrs of age in comparison to those less than 56 yrs (p < 0.05). CONCLUSION: It seems that chest pain is the distinct symptom of achalasia which is affected by sex as well as age and does not relate to the duration of illness, LESP and the type of treatment achalasia patients receive

Does type 2 diabetes influence the risk of oesophageal adenocarcinoma?

Since hyperinsulinaemia may promote obesity-linked cancers, we compared type 2 diabetes prevalence among oesophageal adenocarcinoma (OAC) patients and population controls. Diabetes increased the risk of OAC (adjusted odds ratio 1.59, 95% confidence interval (CI) 1.04–2.43), although the risk was attenuated after further adjusting for body mass index (1.32, 95% CI 0.85–2.05)

Impact of hiatal hernia on histological pattern of non-erosive reflux disease

BACKGROUND: Hiatus hernia (HH) has major pathophysiological effects favoring gastroesophageal reflux and hence contributing to esophageal mucosa injury, especially in patients with severe gastroesophageal disease. However, prospective studies investigating the impact of HH on the esophageal mucosa in non-erosive reflux disease (NERD) are lacking. This study evaluated the association between the presence of (HH) and the histological findings in symptomatic patients with NERD. METHODS: Fifty consecutive patients with gastroesophageal reflux disease (GERD) were enrolled. After conventional endoscopy, Lugol solution was applied and biopsy specimens were obtained. Histological parameters including basal zone hyperplasia, papillary length and cellular infiltration were evaluated. The chi-square test with Yates' correlation was used for comparing discrete parameters between groups. However, Fisher's exact probability test was used where the expected frequencies were lower than 5. Wilcoxon's test for unpaired samples was preferred in cases of semi-quantitative parameters. RESULTS: The presence of HH along with more severe findings (0.01 <P < 0.05) was confirmed in 18 patients. NERD was observed in 29 (58%) patients. Basal zone hyperplasia and loss of glycogen accompanied HH in all cases, and the correlation was significant in NERD (P < 0.001). The remaining histological patterns were similar between erosive reflux disease and NERD in the presence of HH. CONCLUSION: The presence of HH is correlated with more severe endoscopy findings, and predisposes for severe histological abnormality in cases of NERD

Radiofrequency Ablation of Barrett's Esophagus Reduces Esophageal Adenocarcinoma Incidence and Mortality in a Comparative Modeling Analysis

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Ethnicity and gender related differences in extended intraesophageal pH monitoring parameters in infants: a retrospective study

BACKGROUND: Gastroesophageal reflux disease (GERD) is believed to be more common in adult males as compared to females. It also has been shown in adults to be more common in Caucasians. We wanted to determine ethnicity and gender related differences for extended pH monitoring parameters in infancy. METHODS: Extended pH monitoring data (EPM) from infants <1 year of age were reviewed. Results were classified in two groups, as control and Gastroesophageal reflux disease (GERD) group based on the reflux index (RI). The GERD group had RI of equal to or more than 5% of total monitoring period. The parameters of RI, total number of episodes of pH < 4, and the number of episodes with pH < 4 lasting more than 5 minutes were compared by genders and by ethnic groups, Caucasians and African American (AA). RESULTS: There were 569 infants, 388 controls, 181 with GERD (320 males, 249 females; 165 Caucasians, 375 AA). No statistical difference in EPM parameters was detected between genders in both groups. However, Caucasian infants had a significantly higher incidence of GERD than AA infants (p = 0.036). On stratifying by gender, Caucasian females had a significantly higher number of reflux episodes >5 minutes as compared to AA females in the control group (p = 0.05). Furthermore, Caucasian females with GERD showed an overall higher trend for all parameters. Caucasian males had a trend for higher mean number of reflux episodes as compared to AA males in the control group (p = 0.09). CONCLUSION: Although gender specific control data do not appear warranted in infants undergoing EPM, ethnic differences related to an overall increased incidence of pathologic GERD in Caucasian infants should be noted

Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life?

The aim of this study was to evaluate oesophageal function after correction of oesophageal atresia in adults, and to investigate the association between complaints, oesophageal function and quality of life (QoL). Twenty-five adults were included who participated in previous follow-up studies, during which complaints of dysphagia and gastro-oesophageal reflux (GOR), results of upper gastrointestinal endoscopy, oesophageal biopsies and QoL had been collected. Manometry was performed in 20 patients, 24 h pH-measurements were performed in 21 patients. pH-values (sample time 5 s) were calculated using criteria of Johnson and DeMeester. Associations were tested with ANOVA and χ2-tests. Ten patients (48%) reported complaints of dysphagia, seven (33%) of GOR. The amplitude of oesophageal contractions was low (<15 mmHg) in four patients (20%). pH-measurements showed pathological reflux in three patients (14%). Patients reporting dysphagia more often had disturbed motility (P = 0.011), and lower scores on the domains “general health perceptions” (SF-36) (P = 0.026), “standardised physical component” (SF-36) (P = 0.013), and “physical well-being” (GIQLI) (0.047). No other associations were found. This study shows a high percentage of oesophageal motility disturbances and a moderate percentage of GOR after correction of oesophageal atresia. Patients reporting dysphagia, whom more often had disturbed motility, seemed to be affected by these symptoms in their QoL