Amomum subulatum fruits protect against radiation-induced esophagitis by regulating antioxidant status and inflammatory responses.

Radiation esophagitis (RE) is an inimical event that requires proper management while carrying out radiotherapy for thoracic cancers. The present study investigates the protective effect of dry fruits of the culinary and folkloric spice Amomum subulatum against experimental thoracic radiation-induced esophagitis. C57BL/6 mice were subjected to 25 Gy whole thorax irradiation and administered with 250 mg/kg body weight of methanolic extract of A. subulatum dry fruits (MEAS) orally for four consecutive weeks. Changes in tissue antioxidant activities, oxidative stress parameters, expression of antioxidant, inflammation, and fibrosis-related genes were observed. Administration of MEAS boosted antioxidant status, thereby reducing radiation-induced oxidative stress in the esophagus. PCR (polymerase chain reaction) results showed decreased expression of apoptosis, inflammation, and fibrosis-associated genes as well as increased expression of vital cytoprotective and antioxidant genes in MEAS-treated mice, manifesting its protective effect against radiation-induced oxidative stress, inflammatory responses, and fibrosis in the esophagus. Further, histopathology, immunohistochemistry (Cyclooxygenase-2), and Masson's Trichrome staining ascertained the protective effect of MEAS in alleviating radiation-induced esophageal injury. The synergistic effect of bioactive phytochemicals in MEAS with potent antioxidant and anti-inflammatory efficacies might have contributed to its mitigating effect against RE. Taken together, our results ascertained the radioprotective potential of MEAS, suggesting its possible nutraceutical application as a radiation countermeasure.

The Protective Effect of Transit Bipartition and Its Modification Against Sleeve Gastrectomy-Related Esophagitis in a Rodent Model.

BACKGROUND: The protective effect of transit bipartition against esophagitis has not yet been proven. Thus, we investigate and compare the bariatric outcomes and esophagus' histological changes of sleeve gastrectomy (SG), SG with transit bipartition (SG-TB), and the proximal SG-TB (SG-PTB) in a rodent model. METHODS: This study included 45 diabetic Sprague-Dawley rats assigned to one of the four groups, SG-PTB (n = 15), SG-TB (n = 12), SG (n = 10), and SHAM (n = 8). Eight surviving rats from each group were included for further investigation. Histological analysis of the gastroesophageal junction was performed. Body weight, food intake, glucose control, and hormonal changes (glucagon-like peptide-1 and insulin) were assessed before and after surgery in all groups. RESULTS: Preoperatively, no significant differences were observed in food intake, body weight, and fasting blood glucose levels among the groups. Postoperatively, the SG-PTB and SG-TB groups showed significantly superior glucose control compared to the SG group following the gavage of glucose (p < 0.05). Postoperatively, the SG-PTB and SG-TB groups had higher postoperative GLP-1 levels than postoperative SG and SHAM groups. More severe esophageal hyperpapillomatosis (EHP) of the esophageal section was observed in the SG group. The mucosal height of the SG group was significantly higher than that of the SG-PTB, SG-TB, and SHAM groups (p < 0.05). CONCLUSION: The transit bipartition procedure may protect the distal esophagus from histological changes associated with esophagitis. Clinical studies are needed to confirm the anti-reflux effects of transit bipartition.

Prevention and management of acute esophageal toxicity during concomitant chemoradiotherapy for locally advanced lung cancer.

BACKGROUND: Standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC) is concomitant chemoradiotherapy. The survival benefit of combined treatment is partially counterbalanced by an increased rate of acute esophageal toxicity. Several pharmaceutical products are available for prevention and management of esophagitis, including Faringel Plus. AIM: To assess the incidence and the grade, identify the correlations with clinical, dosimetric, and therapeutic variables, and analyse the role of Faringel Plus as a pharmaceutical preventive measure against acute esophageal toxicity. METHODS: Patients with LA-NSCLC treated with concomitant radiochemotherapy were retrospectively reviewed. Acute esophagitis and dysphagia were graded according to Common Terminology Criteria for Adverse Events version 5.0. Clinical, dosimetric, and therapeutic correlations were investigated using χ2 test. RESULTS: Among the 23 analysed patients, 18 (78.3%) and 1 (4.3%) developed G2 and G3 esophagitis, respectively; G1-2 dysphagia were reported in 11 cases (47.8%). No statistically significant correlation between the variables considered and acute esophageal toxicity was identified. In the group of patients who received Faringel Plus as preventive treatment (10 subjects, 43.5%), dysphagia presentation time was significantly longer (p = 0.038); esophagitis onset time was longer and symptoms duration was shorter. Faringel Plus allowed a reduction in the use of analgesic drugs. CONCLUSIONS: Acute mild esophageal toxicity was confirmed to be a common side effect in this setting. No clinical-dosimetric parameter has been demonstrated to be effective in predicting acute esophageal toxicity. The use of Faringel Plus appears effective as a therapeutic and prophylactic tool to manage acute esophageal toxicity.

A randomized trial of sodium alginate prevention of esophagitis in LA-NSCLC receiving chemoradiotherapy: OLCSG1401.

BACKGROUND: Radiation esophagitis is a critical adverse event that needs to be appropriately managed while administering thoracic irradiation. This trial aimed to investigate whether sodium alginate has preventative effects on esophagitis in patients with non-small-cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy (CRT). METHODS: Patients with untreated stage III NSCLC who were eligible for concurrent CRT were randomly assigned at a 1:1:1 ratio to receive one of the following treatments: initial or late use of oral sodium alginate (arms A and B) or water as control (arm C). The primary endpoint was the proportion of patients developing G3 or worse esophagitis. RESULTS: Overall, 94 patients were randomly assigned between February 2014 and September 2018. The study was prematurely terminated because of slow accrual. The proportions of patients with G3 or worse esophagitis were 12.5%, 9.8%, and 19.4% in arms A, B, and C, respectively. Patients receiving sodium alginate had fewer onsets of G3 esophagitis; however, differences compared with arm C were not significant (A vs. C: p = 0.46; B vs. C: p = 0.28). The rates of grade 3 or worse non-hematologic toxicities besides esophagitis were 29%, 26%, and 43% in arms A, B, and C, respectively. Interestingly, compared with arm C, a low rate of febrile neutropenia was observed in arm A (3.1% vs. 19.4%: p = 0.04). CONCLUSIONS: Sodium alginate did not show significant preventative effects on radiation-induced esophagitis in patients with NSCLC. The frequency of CRT-induced febrile neutropenia was lower in the early use sodium alginate arm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier Registry number: UMIN000013133.

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.

A prospective, three-arm, randomized trial of EGCG for preventing radiation-induced esophagitis in lung cancer patients receiving radiotherapy.

BACKGROUND AND PURPOSE: This trial investigated whether epigallocatechin-3-gallate (EGCG), a radioprotector, could be effective in the prevention and treatment of acute radiation-induced esophagitis (ARIE). METHODS AND MATERIALS: This is a phase II study of EGCG combined with chemoradiation in unresectable stage III non-small-cell lung cancer or limited stage small cell lung cancer. Patients were randomized into a prophylactic EGCG group (arm A), a therapeutic EGCG group after the occurrence of esophagitis (arm B) or conventional therapy group (arm C). Esophagitis grades, pain and dysphagia scores were recorded weekly. Adjusted esophagitis index (AEI), pain index (API) and dysphagia index (ADI) were calculated to reflect changes in esophagitis grade, pain score and dysphagia score throughout treatment. RESULTS: A total of 83 patients were eligible for toxicity analysis (arm A vs arm B vs arm C: N = 28:27:28). There was no significant difference in the baseline characteristics among three arms of the patients. The difference in the maximum esophagitis grade among three groups was statistically significant (P = 0.004). The maximum ARIE for patients with EGCG was significantly lower than for those with conventional therapy. The mean AEI of arm A was lower than that of arm B, while the mean AEI of arm C was the highest (arm A vs arm B, P = 0.028; arm B vs arm C, P = 0.002). Furthermore, API and ADI were significantly lower in patients receiving EGCG than in conventionally treated patients. CONCLUSION: The application of EGCG could effectively alleviate acute radiation esophagitis in advanced lung cancer without obvious side effects. Prophylactic application of EGCG had a slight advantage over therapeutic use in treatment of acute esophagitis.

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.

Impact of Chronic Statins Use on the Development of Esophagitis in Patients with Gastroesophageal Reflux Disease.

Background and Aims: We aimed to assess whether chronic statins used (> 6 months) were protective of the development of esophagitis in patients with gastroesophageal reflux disease. In the presence of esophagitis, complications such as strictures, Barrett's esophagus, and adenocarcinoma were the most common. Statins, lipid lowering drugs with a pleiotropic effect, are recently implicated in various pathologies. Nevertheless, the possible impact of statins in esophagitis development has never been assessed. Methods: We performed a retrospective, cross-sectional, single center study that included 4148 gastroesophageal reflux disease patients from 2014 and 2018 at EMMS Nazareth Hospital. We divided the patients into 5 groups. The groups were split into positive control group, which was the nonesophagitis group, and the other 4 groups were A-D (as per Los Angeles classification). Results: Overall, out of the 4148 patients included, 48% were males and 2840 patients were in the control group. In groups A, B, C, and D there were 818, 402, 72, and 16 patients, respectively. Logistic regression analysis revealed that chronic statins usage is protective by preventing development esophagitis (OR 0.463 [95%CI 0.370-0.579], p < 0.0001). NSAIDS use, Hiatus hernia, and H. pylori were promoting factors (OR, 1.362, 1.779, and 1.811; 95% CI, 1.183-1.569, 1.551-2.040, and 1.428-2.298; P<0.0001, P<0.0001, and P<0.0001, respectively). Conclusion: Using chronic statins was protective to the development of esophagitis among GERD patients. Our findings of potential clinical application mandate further randomized controlled trials to better assess the impact of statins on esophagitis.

Physical Activity Protects Against the Risk of Erosive Esophagitis on the Basis of Body Mass Index.

GOAL: To determine whether physical activity lowers the risk for erosive esophagitis on the basis of body mass index (BMI). BACKGROUND: Although previous studies have shown that physical activity is closely associated with erosive esophagitis, these data may be confounded by obesity. STUDY: In this retrospective study, we included 182,409 patients who underwent an upper endoscopy and were diagnosed with erosive esophagitis. The impact of the amount and intensity of physical activity on the risk for erosive esophagitis was analyzed based on BMI groups. Subjects were classified into three BMI groups with equal numbers in each group. RESULTS: Overall, 10.3% (n=18,859) of patients were diagnosed with erosive esophagitis. After adjusting for confounding factors, a greater amount of exercise [lower tertile: odd ratio (OR), 0.86; 95% confidence interval (CI), 0.77-0.96; middle tertile: OR, 0.91; 95%, CI 0.84-1.00; upper tertile: OR, 0.79; 95% CI, 0.73-0.85) and increased exercise intensity (lower tertile, moderate: OR, 0.61; 95% CI, 0.52-0.71; vigorous: OR, 0.51; 95% CI, 0.44-0.58; middle tertile, moderate: OR, 0.62; 95% CI, 0.55-0.70; vigorous: OR, 0.58; 95% CI, 0.51-0.65; upper tertile, moderate: OR, 0.58; 95% CI, 0.53-0.65; vigorous: OR, 0.58; 95% CI, 0.53-0.64) was associated with a decreased risk for erosive esophagitis in all 3 BMI groups. In addition, we observed that increased physical activity intensity notably decreased the risk for erosive esophagitis in subjects performing lesser physical activity, but slightly decreased the risk for erosive esophagitis in subjects performing more physical activity. CONCLUSION: Physical activity is inversely associated with erosive esophagitis.

An esophagus-sparing technique to limit radiation esophagitis in locally advanced non-small cell lung cancer treated by simultaneous integrated boost intensity-modulated radiotherapy and concurrent chemotherapy.

BACKGROUND: To investigate the incidence of radiation esophagitis (RE) and tumor local control using esophagus sparing technique in locally advanced non-small cell lung cancer (LANSCLC) treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) and concurrent chemotherapy. METHODS: Eighty-seven patients with stage IIIA/B NSCLC who received definitive SIB-IMRT and concurrent chemotherapy had been divided into two groups: 1.with esophagus sparing technique; 2.without esophagus sparing technique. Chi-square test was performed to compare sex, clinical stage, histology, concurrent chemotherapy, RE and nutrition status between two groups. T-test was used to compare the dosimetric parameters. Overall survival (OS) and loco-regional failure free survival (LRFS) were calculated by the Kaplan-Meier method and compared by a log-rank test. RESULTS: There were 44 patients in the esophagus sparing group and 43 in the non-sparing group. The incidence of severe RE (Grade 3) was significantly lower in patients with esophagus sparing technique (p = 0.002). Patients in esophagus sparing group had better nutrition status (p = 0.045). With a median follow-up of 18 months (range 1-51 months), the 1-year, 2-year and 3-year OS of all the patients was 86.6, 65.4 and 43.7%. The 1-year, 2-year LRFS was 78.4, 65.9%. OS time (p = 0.301) and LRFS (p = 0.871) was comparable between two groups. CONCLUSIONS: Esophagus-sparing technique is an effective and essential method to limit RE in LANSCLC treated by SIB-IMRT and concurrent chemotherapy without compromising local control.

Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer.

TITLE: Cancer Trials Ireland (ICORG) 06-34: A multi-centre clinical trial using three-dimensional conformal radiation therapy to reduce the toxicity of palliative radiation for lung cancer. NCT01176487. BACKGROUND & PURPOSE: Trials of radiation therapy for the palliation of intra-thoracic symptoms from locally advanced non-small cell lung cancer (NSCLC) have concentrated on optimising fractionation and dose schedules. In these trials, the rates of oesophagitis induced by this "palliative" therapy have been unacceptably high. In contrast, this non-randomised, single-arm trial was designed to assess if more technically advanced treatment techniques would result in equivalent symptom relief and reduce the side-effect of symptomatic oesophagitis. MATERIALS & METHODS: Thirty-five evaluable patients with symptomatic locally advanced or metastatic NSCLC were treated using a three-dimensional conformal technique (3-DCRT) and standardised dose regimens of 39 Gy in 13 fractions, 20 Gy in 5 fractions or 17 Gy in 2 fractions. Treatment plans sought to minimise oesophageal dose. Oesophagitis was recorded during treatment, at two weeks, one month and three months following radiation therapy and 3-6 monthly thereafter. Mean dose to the irradiated oesophagus was calculated for all treatment plans. RESULTS: Five patients (14%) had experienced grade 2 oesophagitis or dysphagia or both during treatment and 2 other patients had these side effects at the 2-week follow-up. At follow-up of one month after therapy, there was no grade two or higher oesophagitis or dysphagia reported. 22 patients were eligible for assessment of late toxicity. Five of these patients reported oesophagitis or dysphagia (one had grade 3 dysphagia, two had grade 2 oesophagitis, one of whom also had grade 2 dysphagia). Quality of Life (QoL) data at baseline and at 1-month follow up were available for 20 patients. At 1-month post radiation therapy, these patients had slightly less trouble taking a short walk, less shortness of breath, did not feel as weak, had better appetite and generally had a better overall quality of life than they did at baseline. They did report being slightly more tired. CONCLUSIONS: This trial is the first of its kind showing that 3-DCRT provides patients with lower rates of oesophageal toxicity whilst yielding acceptable rates of symptom control. (Sponsored by Cancer Trials Ireland (ICORG) Study number 06-34, the Friends of St. Luke's and the St. Luke's Institute of Cancer Research.).

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.

A Randomized Phase 2 Trial of Prophylactic Manuka Honey for the Reduction of Chemoradiation Therapy-Induced Esophagitis During the Treatment of Lung Cancer: Results of NRG Oncology RTOG 1012.

PURPOSE: Randomized trials have shown that honey is effective for the prevention of radiation-induced mucositis in head and neck cancer patients. Because there is no efficacious preventative for radiation esophagitis in lung cancer patients, this trial compared liquid honey, honey lozenges, and standard supportive care for radiation esophagitis. METHODS: The patients were stratified by percentage of esophagus receiving specific radiation dose (V60 Gy esophagus <30% or ≥30%) and were then randomized between supportive care, 10 mL of liquid manuka honey 4 times a day, and 2 lozenges (10 mL of dehydrated manuka honey) 4 times a day during concurrent chemotherapy and radiation therapy. The primary endpoint was patient-reported pain on swallowing, with the use of an 11-point (0-10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). The study was designed to detect a 15% relative reduction of change in NRPS score. The secondary endpoints were trend of pain over time, opioid use, clinically graded and patient-reported adverse events, weight loss, dysphagia, nutritional status, and quality of life. RESULTS: 53 patients were randomized to supportive care, 54 were randomized to liquid honey, and 56 were randomized to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms, which was found to be significant (P=.03), with more patients on the supportive care arm taking opioids. CONCLUSION: Honey as prescribed within this protocol was not superior to best supportive care in preventing radiation esophagitis. Further testing of other types of honey and research into the mechanisms of action are needed.

Lycopene in the Prevention of Radiation-Induced Esophagitis.

We aimed to research whether lycopene (L) could prevent radiation-induced acute esophageal toxicity in Wistar albino rats. 60 rats were placed in five groups as follows: control, L, radiotherapy (RT), L before RT (L + RT), and L before and after RT (L + RT + L). 6 mg/kg bw/day L was administered 7 days in the L group, 7 days before RT in the L + RT group, and 7 days before and after in the L + RT + L group. 35 Gy thoracic RT was performed. Serum L levels were measured, and the esophagi were evaluated histopathologically for intraepithelial degenerative changes-necrosis, vacuole formation, inflammation, regeneration-mitosis, and subepithelial bulla formation. L levels were significantly higher in the L receiving groups. All histopathologic results were significantly worse in the RT group than in the none-RT groups. The L + RT and the L + RT + L groups had better results than the RT group. Grade 2-3 degenerative changes-necrosis and vacuole formation were significantly lesser in the L + RT and the L + RT + L groups than those in the RT group. There was a trend toward decreased subepithelial bulla formation and inflammation in the L + RT and the L + RT + L groups compared to the RT group. Regeneration-mitosis was insignificantly lesser in the L + RT and significantly fewer in the L + RT + L groups than that in the RT group.

Intentional avoidance of the esophagus using intensity modulated radiation therapy to reduce dysphagia after palliative thoracic radiation.

BACKGROUND: Palliative thoracic radiotherapy is an effective technique to alleviate symptoms of disease burden in advanced-stage lung cancer patients. Previous randomized controlled studies demonstrated a survival benefit in patients with good performance status at radiation doses of 35Gy10 or greater but with an increased incidence of esophagitis. The objective of this planning study was to assess the potential impact of esophageal-sparing IMRT (ES-IMRT) compared to the current standard of care using parallel-opposed pair beams (POP). METHODS: In this study, 15 patients with lung cancer treated to a dose of 30Gy in 10 fractions between August 2015 and January 2016 were identified. Radiation treatment plans were optimized using ES-IMRT by limiting the max esophagus point dose to 24Gy. Using published Lyman-Kutcher-Burman normal tissue complication probabilities (LKB-NTCP) models, both plans were evaluated for the likelihood of esophagitis (≥ grade 2) and pneumonitis (≥ grade 2). RESULTS: Using ES-IMRT, the median esophageal and lung mean doses reduced from 16 and 8Gy to 7 and 7Gy, respectively. Using the LKB models, the theoretical probability of symptomatic esophagitis and pneumonitis reduced from 13 to 2%, and from 5 to 3%, respectively. The median normalize total dose (NTD mean) accounting for fraction size for the GTV and PTV of the clinically approved POP plans compared to the ES-IMRT plans were similar. CONCLUSION: Advanced radiotherapy techniques such as ES-IMRT may have clinical utility in reducing treatment-related toxicity in advanced lung cancer patients. Our data suggests that the rate of esophagitis can be reduced without compromising local control.

The effects of oral glutamine on clinical and survival outcomes of non-small cell lung cancer patients treated with chemoradiotherapy.

PURPOSE: To assess the efficacy of oral glutamine (Gln) supplementation on clinical and survival outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC). MATERIALS/METHODS: Between 2010 and 2014, 122 stage III NSCLC patients were retrospectively analyzed. All patients received curative intent chemoradiotherapy (CRT). Prophylactic oral Gln powder was applied at a dose of 10 g tid. Effect of oral Gln supplementation in the prevention of severe (≥grade 2-3) acute radiation-induced esophagitis (ARE) and weight loss, and their relation with overall survival (OS) and disease-free survival (DFS) was measured. RESULTS: Median follow-up was 13.14 months (range; 1.97-55.36). Fifty-six (46%) patients had received oral Gln. Severe ARE was significantly lower in Gln-supplemented group (30% vs 70%; p = 0.002). Gln-free patients demonstrated a higher weight loss (p = 0.0001). In multivariate analysis hemoglobin (hb) level (<12 g/dL; p = 0.01) and nodal stage (N3; p = 0.01) were poor prognostic factors that affect OS; Weight loss (p = 0.06) and Gln-free (p = 0.05) reached nearly significant levels that poorly affect OS. Similarly, nodal stage (N3, p = 0.014) and Gln-free (p = 0.035) were poor prognostic factors that affect DFS. Weight loss (≥2%, p = 0.06) and hb level (<12 g/dL, p = 0.07) reached borderline significance that poorly affect DFS. Nodal stage (N3) was the only poor prognostic factor that affect OS and DFS in univariate analysis (p = 0.01, p = 0.009; respectively). CONCLUSION: Oral Gln supplementation significantly reduces grade 2-3 esophagitis and weight loss and also no negative impact on tumor control and survival outcomes in patients with LA-NSCLC.

Weight loss and waist reduction is associated with improvement in gastroesophageal disease reflux symptoms: A longitudinal study of 15 295 subjects undergoing health checkups.

BACKGROUND: General obesity and abdominal obesity is an established risk factor of gastroesophageal reflux disease (GERD). However, the influence of weight or waist change on improvement of GERD is unclear. Our aim was to investigate if weight loss or waist reduction improves GERD symptoms and esophagitis. METHODS: A retrospective longitudinal study of 15 295 subjects who underwent gastroscopy for a health checkup and reported GERD symptoms between 2011 and 2013, and repeated a checkup until 2014 was conducted. The improvement of GERD symptoms and esophagitis according to weight loss (≥-2, -0.5 to -2 kg/m2 in body mass index [BMI]), waist reduction (≥-5, -0.1 to -0.5 cm) and baseline BMI/waist circumference (WC) categories was assessed using logistic regression. KEY RESULTS: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Among subjects with general obesity (BMI ≥25 kg/m2 ) and decreased ≥2 kg/m2 in BMI, the adjusted odds ratio (OR) of improvement in GERD symptoms was 2.34 (95% confidence interval [CI] 1.70-2.83). Among subjects with abdominal obesity (WC ≥90 cm) and decreased ≥5 cm in WC, the corresponding OR was 2.16 (95% CI 1.56-2.90). There was no association between weight loss or waist reduction and improvement in esophagitis. CONCLUSIONS & INFERENCES: Weight loss or waist reduction was associated with improvement in GERD symptoms only in subjects with general or abdominal obesity. Weight loss or waist reduction will be an important treatment option in obese patients.

Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.

AIM: To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS: Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 µg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 µg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS: BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats). CONCLUSION: Innate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer?: A meta-analysis of 16 randomized controlled trials following the PRISMA guidelines.

BACKGROUND/INTRODUCTION: Aidi injection plus radiotherapy is widely used for lung cancer in China. Can Aidi injection alleviate the toxicity and improve the clinical efficacy of radiotherapy in lung cancer? Has Aidi injection the attenuation and synergistic efficacy to radiotherapy? There is lack of strong evidence to prove it. OBJECTIVES: To reveal its real attenuation and synergistic efficacy to radiotherapy and provide sufficient evidence for adjuvant chemotherapy strategies to lung cancer, we systematically evaluated all related studies. DATA SOURCES: We collected all studies about Aidi injection plus radiotherapy for lung cancer in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese scientific journals full-text database (VIP), Wanfang database, China biological medicine database (CBM) (established to June 2015), and Cochrane Central Register of Controlled Trials (June 2015), evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (5.1.0), extracted data following the PICO principles and synthesized the data by Meta analysis. RESULTS: Sixteen randomized controlled trials (RCTs) with 1192 lung cancer patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR), disease control rate (DCR), and quality of life (QOL) were as follows: 1.54, (1.39,1.70), 1.10 (1.02, 1.19), and 2.13 (1.68, 2.68). The merged RR values and their 95% CI of meta-analysis for myelosuppression and neutropenia, radiation pneumonitis, and radiation esophagitis were as follows: 0.51 (0.38, 0.69), 0.53 (0.42, 0.65), 0.52 (0.41, 0.67), and 0.52 (0.40, 0.68). All were statistically significant. The possibility of publication bias was small which objectively reported the results. CONCLUSIONS: The evidence available indicates that Aidi injection plus radiotherapy can significantly improve the clinical efficacy and QOL of patients with lung cancer. Aidi injection can alleviate the myelosuppression, radiation pneumonitis, and radiation esophagitis of radiotherapy. It has the attenuation and synergistic efficacy to radiotherapy.