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 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.

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.

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.

The role of glutamine supplementation in thoracic and upper aerodigestive malignancies.

In cancer patients, marked glutamine (gln) depletion develops over time. Host tissues (epithelial cells and lymphocytes) that depend upon adequate stores of gln for optimal functioning can be negatively influenced. In addition, radiation and/or chemotherapy cause normal tissues damage that might be enhanced by this depletion effect. The present review evaluates in vivo clinical data about the potential beneficial role of gln administration in the prevention of host tissue toxicity, in a patient group with thoracic and upper aerodigestive malignancies (T&UAM) during cancer treatment. Publications were identified in a systematic review of MEDLINE Database from the last 2 decades (1994-2014) using key search terms and through manual searches. Overall, 13 clinical studies (9 oral/4 parenteral) evaluated the safety and tolerance of gln supply, showing a beneficial effect in the grade, duration of mucositis and esophagitis, decreased gut permeability, and weight loss. Only 1 Phase 1 clinical trial had negative results because the chemo-radiotherapy combined treatment was not feasible. The use of oral gln may especially have an important role in the prevention of acute radiation toxicities, the weight loss and the need for analgesics in patients with T&UAM, especially if the treatment plan includes combined modality therapy with chemo-radiation.

Effect of lycopene against gastroesophageal reflux disease in experimental animals.

BACKGROUND: Lycopene is a robust antioxidant with significant antiulcer activity. Henceforth, the present study was ventured to elucidate the effect of lycopene on experimental esophagitis. METHODS: Groups of rats were subjected to forestomach and pylorus ligation with subsequent treatment with lycopene (50 and 100 mg/kg, po) and pantoprazole (30 mg/kg, po). RESULTS: Treatment with lycopene evidenced sententious physiological protection when scrutinized for pH, acidity (total and free), volume of gastric juices and esophagitis index. Lycopene further embarked diminishing effect on oxidative stress through synchronising lipid and protein peroxidation along with regulating the enzymatic activity of SOD and catalase. Lycopene also modified the levels of immunoregulatory cytokines (IL- 1ß and IL-6) favourably. The dose dependent efficacy of lycopene in the current experimental condition was also attested when exemplified morphologically through scanning electron microscopy. CONCLUSION: From the current line of evidences, it was concluded that lycopene can impart momentous protection against experimental esophagitis by wrapping up the reactive oxygen species and through dual inhibition of the arachidonic acid pathway.

Improving the diagnosis and management of GORD in adults.

Gastro-oesophageal reflux disease (GORD) is defined as a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Many patients with GORD complications such as oesophagitis, and up to a third of patients with Barrett's oesophagus have no reflux or heartburn symptoms. Conversely, patients can be symptomatic even when normal reflux levels are found and there is an absence of mucosal damage. Significant GORD symptoms occur at least once a week in 8.8-26% of Europeans, with equal prevalence of symptoms in men and women. The frequency and severity of symptoms do not accurately predict the degree of oesophageal damage. If patients with GORD also describe symptoms of dyspepsia this should be considered first with H. py/oritesting or direct referral for gastroscopy if the patient is over 55 given the risk of gastric cancer in these patients. Oesophageal disease can account for up to 20% of cases of chronic cough. Symptoms of GORD occur in more than 45% of patients with asthma, and erosive oesophagitis on endoscopy has a 50% higher likelihood of a diagnosis of asthma. GORD is a risk factor for Barrett's oesophagus and oesophageal adenocarcinoma. The risk increases with duration, severity and frequency. Endoscopy should not be routinely offered at initial presentation unless the patient has dysphagia or other symptoms suggestive of upper GI cancer. Smoking cessation and weight loss are beneficial in reducing GORD symptoms. Abdominal obesity causes GORD by elevating intra-abdominal pressure, which promotes reflux and the development of hiatus hernia. GORD symptoms are increased by 70% among daily smokers who have been smoking for more than 20 years.

Protective role of gluteofemoral obesity in erosive oesophagitis and Barrett's oesophagus.

OBJECTIVE: Abdominal obesity has been associated with erosive oesophagitis (EO) and Barrett's oesophagus (BO). As gluteofemoral obesity protects against diabetes mellitus and cardiovascular disease, we hypothesised that gluteofemoral obesity would be inversely associated with EO and BO. DESIGN: We conducted a cross-sectional study on 822 male colorectal cancer screenees who were recruited to also undergo upper endoscopy. An additional 80 patients with BO clinically detected by upper endoscopy referred for clinical indications were recruited shortly after their diagnoses of BO. Logistic regression was used to estimate the effects of abdominal obesity (waist circumference), gluteofemoral obesity (hip circumference) and waist-to-hip ratio (WHR) on EO and BO (vs neither condition). RESULTS: There were 225 cases of either BO or EO and 675 controls. After adjustment for potential confounders, a positive association was observed between waist circumference and BO and/or EO, which became stronger with further adjustment for hip circumference. In contrast, hip circumference was inversely associated with BO and/or EO. Compared with the lowest quartile of WHR, the adjusted ORs were 1.32 (95% CI 0.747 to 2.33) for the 2nd quartile, 1.54 (95% CI 0.898 to 2.63) for the 3rd quartile, and 2.68 (95% CI 1.57 to 4.55) for the highest quartile. Similar results were obtained for BO and EO treated as separate outcomes. CONCLUSIONS: In a population of older, mostly overweight men, the distribution of obesity is associated with the presence of EO and BO. Abdominal obesity appears to increase the risk of these outcomes, whereas gluteofemoral obesity may be protective.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a highly significant, and sometimes dose-limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis. METHODS: A literature search was conducted to identify eligible published articles, based on predefined inclusion/exclusion criteria. Each article was independently reviewed by 2 reviewers. Studies were rated according to the presence of major and minor flaws as per previously published criteria. The body of evidence for each intervention, in each treatment setting, was assigned a level of evidence, based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The literature search identified 8279 papers, 1032 of which were retrieved for detailed evaluation based on titles and abstracts. Of these, 570 qualified for final inclusion in the systematic reviews. Sixteen new guidelines were developed for or against the use of various interventions in specific treatment settings. In total, the MASCC/ISOO Mucositis Guidelines now include 32 guidelines: 22 for oral mucositis and 10 for gastrointestinal mucositis. This article describes these updated guidelines. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis will help clinicians provide evidence-based management of mucositis secondary to cancer therapy.

Increased skin and mucosal toxicity in the combination of vemurafenib with radiation therapy.

BACKGROUND: Palliative radiotherapy is often required for patients with metastatic malignant melanoma in the case of bone or brain metastases. Since BRAF inhibitor therapy is highly efficient in V600-mutated melanomas, there is hesitation to stop it during radiotherapy. Consequently, radiotherapy under simultaneous vemurafenib treatment is frequently needed. CASE REPORT: We report the case of a patient receiving palliative radiotherapy of spinal bone metastases before and during vemurafenib therapy. The skin reactions were quantitatively scored using computer-assisted digital image evaluation. RESULTS: Radiotherapy without vemurafenib was tolerated very well, whereas radiotherapy under simultaneous vemurafenib treatment resulted in accentuated skin reactions. Furthermore, the patient developed dysphagia and had to be hospitalized for parenteral nutrition. In the quantitative analysis, there was a twofold increase in pigmentation and erythema of the irradiated skin area of the thoracic spine when vemurafenib was combined with radiotherapy compared with radiotherapy treatment alone. This is the first reported case of a patient showing no complications during radiotherapy without vemurafenib but remarkable skin and mucosal toxicity under concurrent vemurafenib therapy. Thus, a genetically conditioned individually elevated radiosensitivity can definitely be excluded. Compared with other reported cases, radiosensitization was not limited to the skin, but also affected the esophageal mucosa. CONCLUSION: Vemurafenib is a strong radiosensitizer. Patients receiving radiotherapy under simultaneous vemurafenib treatment should be monitored very closely.

Simultaneous integrated boost intensity-modulated radiotherapy in esophageal carcinoma: early results of a phase II study.

PURPOSE: The safety and efficacy of using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with esophageal squamous cell carcinoma were evaluated in a single-institution phase II setting. METHODS AND MATERIALS: Between June 2007 and October 2009, 45 patients underwent concurrent chemoradiotherapy (n = 27) or radiotherapy alone (n = 18). Two planning target volumes (PTV) were defined for the SIB: PTVC and PTVG, with prescribed doses of 50.4 Gy to the PTVC (1.8 Gy/fraction) and 63 Gy to the PTVG (2.25 Gy/fraction), both given in 28 fractions. RESULTS: At a median follow-up interval of 20.3 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 42.2 and 40.7 %, respectively. The median overall survival time was 21 months; locoregional control rates were 83.3 % at 1 year and 67.5 % at 3 years. According to CTCAE (version 3.0) criteria, none of the patients developed grade 4-5 toxicity. The most common grade 2 and 3 radiation-related toxicity was radiation esophagitis, occurring in 64 % of all patients (but only 13 % as grade 3). No patient developed grade > 2 pulmonary complications. CONCLUSION: SIB-IMRT is a feasible therapeutic approach for esophageal carcinoma patients and provides encouraging locoregional control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

OBJECTIVES: Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. METHODS: Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. RESULTS: Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). CONCLUSIONS: Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Efficacy of glutamine in the prevention of oral mucositis and acute radiation-induced esophagitis: a retrospective study.

Glutamine is a nutraceutic with antioxidant and immune functions that can protect from adverse effects associated with radiation therapy (RT). The aim of this study was to test whether oral glutamine prevents oral mucositis (OM) or acute radiation-induced esophagitis (ARIE) and favors nutritional status. This retrospective, cohort study included patients treated with RT for cancer on head and neck (HN) or chest areas during the 2008-2010 period. Data on glutamine treatment (initiated before RT, during RT, or no glutamine), appearance of mucositis (according to World Health Organization criteria), weight loss (WL) during RT, moderate [body mass index (BMI) <20.5 kg/m(2) or WL > 5%) or severe (BMI < 18.5 kg/m(2) or WL > 10%) malnutrition, and nutritional support were collected. Quantitative data were compared using Student's t-test and analysis of variance, and qualitative data using the chi-square test. The risk difference was calculated with its 95% confidence interval (95% CI). The sample included 117 patients. Overall, glutamine was associated with a significant reduction of mucositis, WL, and enteral nutrition. The risk difference for developing OM in patients receiving glutamine when compared with controls was -9.0% (95% CI = -18.0% to -1.0%), and for ARIE it was -14.0% (95% CI = -26.0% to -1.0%). More of the patients not receiving glutamine developed severe malnutrition when compared with those receiving this supplement, but there were no differences in other outcomes such as interruption of RT, hospitalization, use of opioid analgesics, or death during RT. Glutamine may have a protective effect during RT, reducing the risk and severity of OM and ARIE, preventing weight loss, and reducing the need for nutritional support. Prospective trials are required.

Preventive effect of irsogladine or omeprazole on non-steroidal anti-inflammatory drug-induced esophagitis, peptic ulcers, and small intestinal lesions in humans, a prospective randomized controlled study.

BACKGROUND: Proton-pump inhibitors such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drug-induced upper gastrointestinal mucosal injuries. However, it is unclear which drugs may protect against all NSAID-induced digestive-tract injuries. Here, we compare the efficacy of the gastromucoprotective drug irsogladine with omeprazole in preventing NSAID-induced esophagitis, peptic ulcers, and small-intestinal mucosal injury in healthy subjects. METHODS: Thirty-two healthy volunteers were assigned to an irsogladine group (Group I; n = 16) receiving diclofenac sodium 75 mg and irsogladine 4 mg daily for 14 days, or an omeprazole group (Group O; n = 16) receiving diclofenac sodium 75 mg and omeprazole 10 mg daily for 14 days. Esophagitis and peptic ulcers were evaluated by esophagogastroduodenoscopy and small-intestinal injuries by capsule endoscopy, fecal calprotectin, and fecal occult blood before and after treatment. RESULTS: There was no significant difference between Group I and Group O with respect to the change in lesion score in the esophagus, stomach, and duodenum before and after treatment.NSAID treatment significantly increased the number of small intestinal mucosal breaks per subject by capsule endoscopic evaluation, from a basal level of 0.1 ± 0.3 up to 1.9 ± 2.0 lesions in Group O (p = 0.0002). In contrast, there were no significant changes in the mean number of mucosal breaks before and after co-treatment in Group I (0.3 ± 0.8 to 0.5 ± 0.7, p = 0.62), and the between-group difference was significant (p = 0.0040). Fecal calprotectin concentration, when the concentration before treatment was defined as 1, was significantly increased both in Group O (from 1.0 ± 0.0 to 18.1 ± 37.1, p = 0.0002) and Group I (from 1.0 ± 0.0 to 6.0 ± 11.1, p = 0.0280); the degree of increase in Group O was significantly higher compared with that in Group I (p<0.05). In addition, fecal occult blood levels increased significantly in Group O (p = 0.0018), but there was no change in Group I (p = 1.0), and the between-group difference was significant (p = 0.0031). CONCLUSION: Irsogladine protected against NSAID-induced mucosal injuries throughout the gastrointestinal tract, from esophagus to small intestine, significantly better than omeprazole. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (Registry ID number; UMIN000008114).

Gastric ischemic conditioning increases neovascularization and reduces inflammation and fibrosis during gastroesophageal anastomotic healing.

BACKGROUND: The incidence of anastomotic leak and stricture after esophagectomy remains high. Gastric devascularization followed by delayed esophageal resection has been proposed to minimize these complications. We investigated the effect of ischemic conditioning duration on anastomotic wound healing in an animal model of esophagogastrectomy. METHODS: North American opossums were randomized to four study groups. Group A underwent immediate resection and gastroesophageal anastomosis. Groups B, C, and D were treated with delayed resection and anastomosis after a gastric ischemic conditioning period of 7, 30, and 90 days, respectively. Gastric conditioning was performed by ligating the left, right, and short gastric vessels. An intraabdominal esophagogastric resection and anastomosis was performed, followed by euthanasia 10 days later. Outcome variables included anastomotic bursting pressure, microvessel concentration, tissue inflammation, and collagen deposition. RESULTS: Twenty-four opossums were randomized to groups A (n = 7), B (n = 8), C (n = 5), and D (n = 4). Subclinical anastomotic leak was discovered at necropsy in 5 animals: 3 in group A, and 1 each in groups B and C (p = 0.295). The anastomotic bursting pressure did not differ significantly between groups (p = 0.545). A 7 day ischemic conditioning time did not produce increased neovascularity (p = 0.900), but animals with a 30 day conditioning time showed significantly increased microvessel counts compared to unconditioned animals (p = 0.016). The degree of inflammation at the healing anastomosis decreased significantly as the ischemic conditioning period increased (p = 0.003). Increasing delay interval was also associated with increased muscularis propria preservation (p = 0.001) and decreased collagen deposition at the healing anastomosis (p = 0.020). CONCLUSIONS: Animals treated with 30 days of gastric ischemic conditioning showed significantly increased neovascularity and muscularis propria preservation and decreased inflammation and collagen deposition at the healing anastomosis. These data suggest that an ischemic conditioning period longer than 7 days is required to achieve the desired effect on wound healing.

Analysis of esophageal-sparing treatment plans for patients with high-grade esophagitis.

We retrospectively generated IMRT plans for 14 NSCLC patients who had experienced grade 2 or 3 esophagitis (CTCAE version 3.0). We generated 11-beam and reduced esophagus dose plan types to compare changes in the volume and length of esophagus receiving doses of 50, 55, 60, 65, and 70 Gy. Changes in planning target volume (PTV) dose coverage were also compared. If necessary, plans were renormalized to restore 95% PTV coverage. The critical organ doses examined were mean lung dose, mean heart dose, and volume of spinal cord receiving 50 Gy. The effect of interfractional motion was determined by applying a three-dimensional rigid shift to the dose grid. For the esophagus plan, the mean reduction in esophagus V50, V55, V60, V65, and V70 Gy was 2.8, 4.1, 5.9, 7.3, and 9.5 cm(3), respectively, compared with the clinical plan. The mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 2.0, 3.0, 3.8, 4.0, and 4.6 cm, respectively. The mean heart and lung dose decreased 3.0 Gy and 2.4 Gy, respectively. The mean decreases in 90% and 95% PTV coverage were 1.7 Gy and 2.8 Gy, respectively. The normalized plans' mean reduction of esophagus V50, V55, V60, V65, and V70 Gy were 1.6, 2.0, 2.9, 3.9, and 5.5 cm(3), respectively, compared with the clinical plans. The normalized plans' mean reductions in LE50, LE55, LE60, LE65, and LE70 Gy were 4.9, 5.2, 5.4, 4.9, and 4.8 cm, respectively. The mean reduction in maximum esophagus dose with simulated interfractional motion was 3.0 Gy and 1.4 Gy for the clinical plan type and the esophagus plan type, respectively. In many cases, the esophagus dose can be greatly reduced while maintaining critical structure dose constraints. PTV coverage can be restored by increasing beam output, while still obtaining a dose reduction to the esophagus and maintaining dose constraints.

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.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. METHODS: The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. RESULTS: Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4-5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. CONCLUSION: In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.

The effectiveness of erythromycin in reducing stent-related tissue hyperplasia: an experimental study with a rat esophageal model.

BACKGROUND: Erythromycin is not only a potent antibiotic; it also has effects of reduction of inflammation and suppression of protein synthesis. PURPOSE: To evaluate the impact of erythromycin on tissue hyperplasia after stent placement in a rat esophageal model. MATERIAL AND METHODS: A total of 21 rats were included. After placement of self-expanding stents in the mid esophagus, the rats were divided into two experimental groups and one control group. The rats in the experimental groups received daily intraperitoneal injections of erythromycin for 5 weeks; 4 mg/kg (group A, n = 7) and 8 mg/kg (group B, n = 7). Those in the control group (n = 7) received 1 mL of saline intraperitoneally. After sacrifice, histologic analysis was done for thickness of the papillary projection, granulation tissue area, percentage of granulation tissue area, and degree of inflammatory cell infiltration. The statistical significance of differences between groups was assessed by Mann-Whitney U test. RESULTS: Tissue hyperplasia as reflected in thickness of papillary projection, granulation tissue area, and percentage of granulation tissue area, was higher in the control group than in the experimental groups, although there was no statistical significance (P = 1.00, 0.332, and 0.263, respectively). However, degree of inflammatory cell infiltration was significantly lower in the experimental groups than the control group (P = 0.025), and the higher dosage of erythromycin reduced inflammatory cell infiltration significantly (P = 0.037). CONCLUSION: Intraperitoneal administration of erythromycin is very effective in reducing inflammation after stent placement in a rat esophageal model but has no significant effect on granulation tissue formation.

[Esophagitis during immunosuppression]. / Ösophagitis unter Immunsuppression.

Esophagitis due to cytomegalovirus (CMV) has mostly been described in patients with acquired immunodeficiency syndrome (AIDS). Distal and hemorrhagic ulcerations are characteristic. A CMA esophagitis can, however, also occur in patients with no human immunodeficiency virus (HIV) infection as a complication of immunosuppressive therapy. In the case example presented here the disease was due to an excessive dosage of prednisolone medication over a period of many years. In all published cases of CMV esophagitis with rheumatic diseases, there was also a high dosage of glucocorticoid medication. To avoid complications regular rheumatological screening controls and adjustment of immunosuppressive therapy are therefore important to maintain control of the disease with low dosage glucocorticoids.