Transoral incisionless fundoplication for recurrent symptoms after laparoscopic fundoplication.

BACKGROUND: Revision of a failed laparoscopic fundoplication carries higher risk of complication and lower chance of success compared to the original surgery. Transoral incisionless fundoplication (TIF) may be an endoscopic alternative for select GERD patients without need of a moderate/large hiatal hernia repair. The aim of this study was to assess feasibility, efficacy, and safety of TIF 2.0 after failed laparoscopic Nissen or Toupet fundoplication (TIFFF). METHODS: This is a multicenter retrospective cohort study of patients who underwent TIFFF between September 2017 and December 2020 using TIF 2.0 technique (EsophyX Z/Z+) performed by gastroenterologists and surgeons. Patients were included if they had (1) recurrent GERD symptoms, (2) pathologic reflux based upon pH testing or Grade C/D esophagitis or Barrett's esophagus, and (3) hiatal hernia ≤ 2 cm. The primary outcome was improvement in GERD Health-Related Quality of Life (GERD-HRQL) post-TIFFF. The TIFFF cohort was also compared to a similar surgical re-operative cohort using propensity score matching. RESULTS: Twenty patients underwent TIFFF (median 4.1 years after prior fundoplication) and mean GERD-HRQL score improved from 24.3 ± 22.9 to 14.75 ± 21.6 (p = 0.014); mean Reflux Severity Index (RSI) score improved from 14.1 ± 14.6 to 9.1 ± 8.0 (p = 0.046) with 8/10 (80%) of patients with normal RSI (< 13) post-TIF. Esophagitis healed in 78% of patients. PPI use decreased from 85 to 55% with 8/20 (45%) patients off of PPI. Importantly, mean acid exposure time decreased from 12% ± 17.8 to 0.8% ± 1.1 (p = 0.028) with 9/9 (100%) of patients with normalized pH post-TIF. There were no statistically significant differences in clinical efficacy outcomes between TIFFF and surgical revision, but TIFFF had significantly fewer late adverse events. CONCLUSION: Endoscopic rescue with TIF is a safe and efficacious alternative to redo laparoscopic surgery in symptomatic patients with appropriate anatomy and objective evidence of persistent or recurrent reflux.

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.

Efficacy of DA-5204 (Stillen 2X) for patients with gastroesophageal reflux disease: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND/AIM: Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90 mg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone. METHODS: This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40 mg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40 mg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire. RESULTS: Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (P < .001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all P > .05). CONCLUSION: Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.

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.

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.

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.

Effect of compound Zhuye Shigao Granule ( ) on acute radiation-induced esophagitis in cancer patients: A randomized controlled trial.

OBJECTIVE: To observe the efficacy and safety of the Chinese medicine (CM) Compound Zhuye Shigao Granule (, CZSG) on acute radiation-induced esophagitis (ARIE) in cancer patients. METHODS: In a blinded, randomized, Kangfuxin Solution (, KFX)-controlled, single-centre clinical trial, 120 patients with lung, esophagus or mediastinal cancer were prospectively enrolled and assigned to the treatment group (60 cases) and control group (60 cases) by the random number table method. All patients received concurrent or sequential radiotherapy (2 Gy per day, 5 times per week, for 4 weeks) and were treated for 4 weeks since the radiation therapy. Patients in the treatment group were given 12 mg CZSG orally, thrice daily, while patients in the control group were given 10 mL KFX orally, thrice daily. The major indicators were observed, including the incidence and grade of esophagitis, time of occurrence and duration. Minor indicators were changes of CM symptoms, weight and Karnofsky Performance Status (KPS) Scale during 4 weeks from the beginning, recorded once a week. Blood routine examination and hepatorenal function were detected at the 2nd and 4th weeks. RESULTS: The incidence and grade of ARIE were significantly decreased in the treatment group compared with the control group (P<0.05). CZSG appeared to significantly delay the time of ARIE occurrence and reduce the duration compared with KFX (P<0.05). The scores of CM symptoms, KPS and weight were improved significantly in the treatment group compared with the control group (P<0.05). There were no blood routine and hepatorenal function abnormal or obvious side-effects in both groups. Hemoglobin was improved and neutrophil and interleukin 6 were decreased in both groups after 4-week treatment compared with before treatment (P<0.05), and there was no significant difference between the two groups (P>0.05). CONCLUSIONS: CZSG can decrease the incidence and grade of ARIE, delay the time of occurrence, reduce duration and alleviate the damage of ARIE. It is safe and effective in the prevention and cure of ARIE.

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.

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.

Planned Esophagectomy after Neoadjuvant Hyperthermo-Chemoradiotherapy using Weekly Low-Dose Docetaxel and Hyperthermia for Advanced Esophageal Carcinomas.

BACKGROUND/AIMS: The optimal treatment for locally advanced esophageal carcinoma has not yet been determined. We report results of neoadjuvant hyperthermo-chemoradiotherapy (HCRT) using weekly low-dose docetaxel followed by surgery in patients with advanced esophageal squamous cell carcinoma. METHODOLOGY: Twenty-four patients were enrolled. 7 patients were considered to have inoperable tumors or rejected surgery after HCRT, and the remaining 17 patients had an esophagectomy. Clinical responses, HCRT toxicity and survival after surgery were evaluated. RESULTS: In the 24 patients, the response rate was 41.7%. The pathological complete response (pCR) rate was 17.6% in the 17 patients. HCRT toxicity grade 2 occurred in six patients (25.0%: esophagitis, 4; leukopenia, 6; neutropenia, 4) and grade 3 (pneumonia) in 3 patients (12.5%). The 3- and 5-year survival rates were 56.3% and 50.0%, respectively. When the patients were divided into a pCR group and a pathological partial response (pPR) group, the 3-year survival rates were 66.7% and 42.9% and the 5-year survival rates were 66.7% and 42.9%, respectively (log-rank P = .5842). CONCLUSIONS: Esophagectomy after docetaxel HCRT may have potential for prolonging survival in patients with locally advanced esophageal cancer. A larger randomized, controlled study will be required to confirm the benefit of esophagectomy after HCRT.

Effect of Zhuyeshigao granule on tumor necrosis factor-alpha and interleukins serum protein levels in rats with radiation esophagitis.

OBJECTIVE: To investigate the effects of Zhuyeshigao granule (ZSG) on tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-2, IL-6, and IL-8 in rats with radiation esophagitis. METHODS: Fifty Wistar rats were randomly divided into five groups (10 rats in each group): control (without radiation), saline-treated, and low, medium, and high-dose ISG-treated groups. Rats were given normal saline (10 mL/kg) or 1.15, 2.3, or 4.6 g/kg ZSG by intragastric administration once a day for 7 days. A rat model of radiation esophagitis was established by local irradiation of Co60 (490.25 cGy/min, totaling 30 Gy). The administration of ZSG was continued for another 7 days and on the 7th day post-irradiation, inferior vena cava blood was collected. The serum was separated, and TNF-alpha, IL-1, IL-2, IL-6, and IL-8 protein levels were determined. RESULTS: Inflammatory response factors were found in the serum of each group. However, levels in ZSG-treated groups were significantly lower than in the saline-treated group (P < 0.05). CONCLUSION: ZSG may prevent the development of radiation esophagitis, perhaps by inhibiting the generation and release of the inflammatory response factors TNF-alpha, IL-1, IL-2, IL-6, and IL-8.

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.

Pain­relieving effect of a compound isolated from white peony root oral liquid on acute radiation­induced esophagitis.

Acute radiation­induced esophagitis (ARIE) is a common complication of radiotherapy. The aim of this study was to clarify the molecular mechanism of pain relief by the compound of white peony root oral liquid (cWPROL) in ARIE. An animal model of ARIE was established and either cWPROL or a mixture of lidocaine, dexamethasone and gentamycin (mLDG) was administered. We indirectly observed rat symptoms of pain by recording the weight of food and the volume of water consumed by the rats, along with changes in body weight. Additionally, the expression levels of substance P (SP) in the esophageal tissues were detected by immunohistochemistry. It was demonstrated that cWPROL was able to release the pain of ARIE by decreasing the expression of SP; this may be one of the molecular mechanisms via which cWPROL induces pain relief.

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.

Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-α gene, with chemoradiotherapy in locally advanced esophageal cancer. OBJECTIVES: To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic. DESIGN/INTERVENTION: Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 10(8) to 4 × 10(11) particle units (PU), were given in combination with cisplatin 75 mg/m(2) and intravenous 5-fluorouracil 1000 mg/m(2)/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment. SETTING: U.S. multicenter study. PATIENTS: Patients with stage II and III esophageal cancer were enrolled. MAIN OUTCOME MEASUREMENTS: Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival. RESULTS: Twenty-four patients with a median age of 61 years were enrolled; 88% of the patients were men, 21% were stage II, and 79% were stage III. Six (29%) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54%), fever (38%), nausea (29%), vomiting (21%), esophagitis (21%), and chills (21%). At the top dose of 4 × 10(11) PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3- and 5-year OS rates and disease-free survival rates were 54% and 41% and 38% and 38%, respectively. LIMITATIONS: We included primarily adenocarcinoma. CONCLUSIONS: Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 10(10) PU and is associated with long survival. This regimen warrants additional studies.