Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial.

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%-30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p < .03) but not in head and neck specific symptom severity (1.2 vs 1.1, p < .60) nor in symptom interference (2.1 vs 1.7, p < .22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus.Clinical trial information. NCT01952847, and date of registration is September 30, 2013.

Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer.

BACKGROUND: Complications related to concurrent chemoradiotherapy (CCRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with advanced non-small cell lung cancer (NSCLC). We designed a prospective randomized study to assess the impact of glutamine (GLN) supplementation in preventing CCRT-induced toxicities of advanced NSCLC patients. METHODS: From September 2014 to September 2015, 60 patients diagnosed with NSCLC were included to the study. Thirty patients (50%) received prophylactic powdered GLN orally at a dose of 10 g/8 h. The prescribed radiation dose to the planning target volume was 30 Gy in 2-Gy fractions. The endpoints were radiation-induced esophagitis, mucositis, body weight loss, overall survival and progression-free survival. RESULTS: The 60 patients with NSCLC included 42 men and 18 women with a mean age ±â€Šstandard deviation of 60.3 years ±â€Š18.2 (range, 44-78 years).At a median follow-up of 26.4 months (range 10.4-32.2), all patients tolerated GLN well. A administration of GLN was associated with a decrease in the incidence of grade 2 or 3 ARIE (6.7% vs 53.4% for Gln+ vs Gln-; P = .004). GLN supplementation appeared to significantly delay ARIE onset for 5.8 days (18.2 days vs 12.4 days; P = .027) and reduced incidence of weight loss (20% vs 73.3%; P = .01). DISCUSSION: Our study suggests a beneficial effect of oral glutamine supplementation for the prevention from radiation-induced injury and body weight loss in advanced NSCLC patients who receiving CCRT.

Factors influencing the outcome of magnetic sphincter augmentation for chronic gastroesophageal reflux disease.

OBJECTIVES: Magnetic sphincter augmentation (MSA) is a surgical treatment option for patients with gastroesophageal reflux disease (GERD). MSA consistently improves quality of life, maintains freedom from PPIs, and objectively controls GERD. However, up to 24% of patients did not achieve these outcomes. We sought to identify factors predicting outcomes after MSA placement with the aim of refining selection criteria. METHODS: We retrospectively analyzed clinical, endoscopic, manometric, pH data, and intraoperative factors from two databases: Pivotal Trial (N = 99) and our prospectively maintained esophageal database (N = 71). A priori outcomes were defined as excellent (GERD-HRQL <5, no PPI, no esophagitis), good (GERD-HRQL 6-15, no PPI, grade A esophagitis), fair (GERD-HRQL 16 to 25, PPI use, grade B esophagitis), and poor (GERD-HRQL >25, PPI use, grade C/D esophagitis). Univariable and multivariable logistic regression analyses were performed to determine predictors of achieving an excellent/good outcome. RESULTS: A total of 170 patients underwent MSA with a median age of 53 years, [43-60] and a median BMI of 27 (IQR = 24-30). At baseline, 93.5% of patients experienced typical symptoms and 69% atypical symptoms. Median DeMeester score was 37.9 (IQR 27.9-51.2) with a structurally intact sphincter in 47%. Esophagitis occurred in 43%. At 48 [19-60] months after MSA, excellent outcomes were achieved in 47%, good in 28%, fair in 22%, and poor in 3%. Median DeMeester score was 15.6 (IQR = 5.8-26.6), esophagitis in 17.6% and daily PPI use in 17%. At univariable analysis, excellent/good outcomes were negatively impacted by BMI, preoperative LES residual pressure, Hill grade, and hiatal hernia. At multivariable analysis, BMI >35 (OR = 0.05, 0.003-0.78, p = 0.03), structurally defective LES (OR = 0.37, 0.13-0.99, p = 0.05), and preoperative LES residual pressure (OR = 0.89, 0.80-0.98, p = 0.02) were independent negative predictors of excellent/good outcome. CONCLUSIONS: Magnetic sphincter augmentation results in excellent/good outcomes in most patients but a higher BMI, structurally defective sphincter, and elevated LES residual pressure may prevent this goal.

Association between coffee or tea drinking and Barrett's esophagus or esophagitis: an Italian study.

BACKGROUND/OBJECTIVES: Only a few papers have treated of the relationship between Barrett's esophagus (BE) or erosive esophagitis (E) and coffee or tea intake. We evaluated the role of these beverages in BE and E occurrence. SUBJECTS/METHODS: Patients with BE (339), E (462) and controls (619) were recruited. Data on coffee and tea and other individual characteristics were collected using a structured questionnaire. RESULTS: BE risk was higher in former coffee drinkers, irrespective of levels of exposure (cup per day; ⩽1: OR=3.76, 95% CI 1.33-10.6; >1: OR=3.79, 95% CI 1.31-11.0; test for linear trend (TLT) P=0.006) and was higher with duration (>30 years: OR=4.18, 95% CI 1.43-12.3; TLT P=0.004) and for late quitters, respectively (⩽3 years from cessation: OR=5.95, 95% CI 2.19-16.2; TLT P<0.001). The risk of BE was also higher in subjects who started drinking coffee later (age >18 years: OR=6.10, 95% CI 2.15-17.3). No association was found in current drinkers, but for an increased risk of E in light drinkers (<1 cup per day OR =1.85, 95% CI 1.00-3.43).A discernible risk reduction of E (about 20%, not significant) and BE (about 30%, P<0.05) was observed in tea drinkers. CONCLUSIONS: Our data were suggestive of a reduced risk of BE and E with tea intake. An adverse effect of coffee was found among BE patients who had stopped drinking coffee. Coffee or tea intakes could be indicative of other lifestyle habits with protective or adverse impact on esophageal mucosa.

Alcohol and tea consumption are associated with asymptomatic erosive esophagitis in Taiwanese men.

OBJECTIVE: Asymptomatic erosive esophagitis (AEE) is commonly found in men, and might be a risk factor of developing esophageal adenocarcinoma. We aimed to determine if specific dietary habits increase the risk of AEE in asymptomatic Taiwanese men. METHODS: We recruited male adults undergoing upper gastrointestinal endoscopy for health check. We excluded subjects with reflux symptoms, or taking anti-reflux medications or drugs that potentially impair lower esophageal sphincter function or cause mucosal injury. The frequency of consuming reflux-provoking diets including alcohol, tea, coffee, tomato/citric juice, chocolate, sweet food, and spicy food was assessed. The erosive esophagitis was diagnosed based on the Los Angeles Classification after endoscopy. Frequent consumption of a specific diet was defined as ≥4 days/week of consuming that diet. RESULTS: A total of 1256 participants were recruited. After excluding 424 ineligible subjects, AEE was identified in 180 (22%) among 832 asymptomatic subjects. The risk of AEE increased with the number of days per week of consuming alcohol or tea: nondrinkers (19%, 17%), occasional drinkers (<1 day/week; 19%, 15%), regular drinkers (1-3 days/week; 26%, 21%), frequent drinkers (4-6 days/week; 32%, 22%), and daily drinkers (42%, 28%), respectively (trend test P < 0.001 for both). Multivariate analysis showed that hiatus hernia (adjusted odds ratio (aOR) 5.0, 95% confidence interval (CI) 2.6-9.6), drinking alcohol ≥4 days/week (aOR 2.3, 95% CI 1.3-4.0), and drinking tea ≥4 days/week (aOR 1.6, 95% CI 1.1-2.3) are independent risk factors of AEE. The risk of AEE was 3.8 times greater for those drinking both alcohol and tea ≥4 days/week than the non-drinkers. CONCLUSIONS: Frequent alcohol and tea consumption increased the risk of AEE in Taiwanese men.

Predictive factors of silent reflux in subjects with erosive esophagitis.

BACKGROUND: Asymptomatic erosive esophagitis by definition is a condition lacking any reflux symptom. AIMS: We aimed to investigate the prevalence of asymptomatic erosive esophagitis in a general population undergoing periodic health checkup. METHODS: Consecutive subjects undergoing a medical checkup were enrolled for evaluation of reflux disease with upper endoscopy and a validated reflux questionnaire. The presence and severity of erosive esophagitis were evaluated. In all subjects, demographic characteristics and biochemical data were recorded, and sleep and psychological characteristics were assessed by means of self-administered Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. RESULTS: Of 2568 subjects eligible for this study, erosive esophagitis was found in 676 subjects (26.3%), in whom the proportions of asymptomatic and symptomatic erosive esophagitis were 59.2% (400 subjects) and 40.8% (276 subjects) respectively. At a univariate analysis, it was found that asymptomatic erosive esophagitis subjects were more frequently of female gender, of older age, with a lower level of education. They also showed less alcohol and tea consumption, less depression, less anxiety, lower serum level of triglyceride, and lower prevalence of metabolic syndrome. Multivariate analysis revealed that female sex (OR = 1.645, p = 0.0146) was a positive predictive factor for asymptomatic erosive esophagitis, whereas higher level of education (OR = 0.564, p = 0.044), higher Taiwanese Depression Questionnaire score (OR = 0.922, p < 0.001), and the presence of metabolic syndrome (OR = 0.625, p = 0.0379) were negative predictive factors. CONCLUSIONS: Asymptomatic erosive esophagitis is a common feature in otherwise healthy subjects and is independently associated with female gender, lower education level, less depression, and lower prevalence of metabolic syndrome.

Endoscopic screening for precancerous lesions of the esophagus in a high risk area in Northern Iran.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major health problem in many developing countries including Iran. ESCC has a very poor prognosis, largely due to late diagnosis. As a first step in developing an early detection and treatment program, we conducted a population-based endoscopic screening for ESCC and its precursor lesion, esophageal squamous dysplasia (ESD) in asymptomatic adults from Golestan Province, northern Iran, a high-risk area for ESCC, to evaluate the feasibility of such a program and to document the prevalence and risk factor correlates of ESD. METHODS: This cross-sectional study was conducted among participants of the Golestan Cohort Study (GCS), a population-based cohort of 50,000 adults in eastern Golestan Province. Randomly selected GCS participants were invited by telephone. Those who accepted were referred to a central endoscopy clinic. Eligible subjects were consented and then asked to fill in a brief questionnaire. Detailed information about selected risk factors was obtained from the GCS main database. Endoscopic examination with Lugol's iodine staining was performed, biopsies were taken from unstained lesions as well as the normally stained mucosa of the esophagus, and the biopsies were diagnosed by expert pathologists according to previously described criteria. RESULTS: In total, 1906 GCS subjects were invited, of whom only 302 subjects (15.8%) were successfully enrolled. Esophagitis (29.5%) and ESD (6.0%) were the most common pathological diagnoses. Turkmen ethnicity (adjusted OR = 8.61; 95%CI: 2.48-29.83), being older than the median age (OR = 7.7; 95% CI: 1.99-29.87), and using deep frying cooking methods (OR = 4.65; 95%CI: 1.19-18.22) were the strongest predictors for ESD. There were significant relationships between esophagitis and smoking (p-value<0.001), drinking hot tea (P value = 0.02) and lack of education (P value = 0.004). CONCLUSION: We observed a low rate for participation in endoscopic screening. Overall prevalence of ESD was 6.0%. Developing non-endoscopic primary screening methods and screening individuals with one or more risk factors may improve these rates.

Correlation between eosinophilic oesophagitis and aeroallergens.

BACKGROUND: Aeroallergens have been implicated in the pathogenesis of eosinophilic oesophagitis. AIM: To determine whether a seasonal variation exists in the diagnoses of eosinophilic oesophagitis and whether there is a correlation with seasonal pollen count. METHODS: A retrospective review was performed from January 2006 to November 2008 to identify eosinophilic oesophagitis patients. Cases were classified by endoscopic date. Daily pollen counts for grass, trees and weeds were obtained from a certified counting station. Per cent of eosinophilic oesophagitis cases were collated seasonally and compared with mean pollen counts for grass, trees and weeds during the same time period. RESULTS: A total of 127 eosinophilic oesophagitis cases were identified (median age 41, range 19-92 years, 84% men). The highest percentage of cases (33.0%; Binomial P = 0.022) was diagnosed in the spring, while the least percentage (16%; Binomial P = 0.0.010) occurred in the winter. There was a significant association between per cent eosinophilic oesophagitis cases diagnosed seasonally and mean grass pollen count (r(s) = 1.000, P < 0.01), but not with trees (r(s) = 0.400, P = 0.600) or weeds (r(s) = 0.800, P = 0.200). CONCLUSIONS: A seasonal variation was seen in the diagnosis of eosinophilic oesophagitis which correlated with pollen counts. These findings have important implications regarding the pathogenesis of eosinophilic oesophagitis, suggesting a potential role for aeroallergens.

Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters.

BACKGROUND: The purpose of this study was to evaluate the efficacy of oral glutamine in the prevention of acute radiation-induced esophagitis (ARIE) and weight loss in lung carcinoma patients, and to determine the clinical/dosimetric predictors of ARIE. PATIENTS AND METHODS: Data from 41 patients with stage III lung carcinoma treated with thoracic irradiation were retrospectively analyzed. Twenty-two patients (53.6%) received prophylactic powdered glutamine in doses of 10g/8h. Prescribed radiation dose to planning target volume was 60Gy, in 30 fractions, 5 days/week. The primary endpoint included the ARIE incidence and its correlation with clinical/dosimetric factors relative to treatment with glutamine. RESULTS: Glutamine was well tolerated. Grade 2 or 3 ARIE occurred in 20 (48.8%) of 41 patients: seven in the glutamine-supplemented group, and 13 in the glutamine-free group (p=0.002). All seven patients with grade 3 esophagitis were in the glutamine-free group (36.8% vs. 0%). Glutamine supplementation appeared to significantly delay ARIE onset for six days (22 days vs. 16 days; p=0.002). Glutamine-supplemented patients demonstrated a lower incidence of grade 2 or 3 ARIE (27.2%), and gained weight during radiotherapy (p=0.04). V55 was the only dosimetric parameter that correlated with the severity of ARIE in glutamine-free patients: a V55 of <35% had a 31% risk of ARIE grade 2 or 3, and the risk increased to 76% with a V55 of >or=35% (p=0.01). CONCLUSION: This schedule and dosage of glutamine may be beneficial in the prevention of ARIE and weight loss in lung cancer patients undergoing thoracic irradiation.

Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer.

This intervention trial carried out in Uzbekistan (former USSR) in an area with a high incidence of oral and esophageal cancer involved random allocation of 532 men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one of four arms in a double-blind, two-by-two factorial design, with active arms defined by the administration of (a) riboflavin; (b) a combination of retinol, beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene was 40 mg/d. Men in the trial were followed for 20 months after randomization. The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and/or protect against progression of oral leukoplakia and esophagitis, conditions considered to be precursors of cancer of the mouth and esophagus. A significant decrease in the prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95% confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups, although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol, beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary analysis not based on the randomized design revealed a decrease in the prevalence of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20 months of treatment. Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95% CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels, respectively. A decrease in risk, also statistically not significant, was observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These results were based on levels of vitamins in blood drawn after 20 months of treatment.