Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures.

PURPOSE: This study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy. METHODS: Eighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms' severity related to hyposalivation. RESULTS: All patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients' self-assessment, with a median duration of 12 months (range, 3-36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7-18 points) to 7 points (range 4-13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04). CONCLUSION: Pilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Clinical factors, management, and outcomes of children under 3 years old with central nervous system tumors: single-center experience.

PURPOSE: Children under 3 years old represent a notable portion, about 25 to 30%, of all central nervous system tumor (CNS) cases. Their clinical course, prognosis, and treatment significantly differ from older children. This single-center retrospective study aims to comprehensively analyze survival factors in children under three diagnosed with CNS tumors. METHODS: Between April 2012 and December 2023, cases under 3 years of age with CNS tumors diagnosed at our center were retrospectively evaluated. RESULTS: Among 279 CNS tumor cases, 42 (15%) were evaluated. The 5-year overall and event-free survival rates were 67.4% (95% CI 47.5-81.1) and 39.8% (95% CI 24.2-55.0), respectively. Gender, symptom onset to diagnosis time, pathological neurological findings at diagnosis, and tumor location did not significantly impact survival (p > 0.05). However, cases with neurological symptoms showed significantly higher event-free survival rates (p < 0.05). Patients with embryonal tumors, metastases, inability for total surgical excision, relapsed/progressive diseases, and who under 1 year old had significantly lower survival rates (p < 0.05). Radiotherapy timing did not affect survival (p > 0.05). Event-free survival rates remained unchanged after the third year. CONCLUSION: The current treatments have been observed to have a positive impact on survival rates. Nonetheless, there is a need for novel treatments for patients with embryonal tumors, metastases, aged under 1 year, and those where total surgical excision is not feasible or in cases with progressive/relapse disease. This study underscores the importance of the first 3 years regarding relapse, progression, or mortality risk.

An Investigation of the Role of Phase Angle in Malnutrition Risk Evaluation and Clinical Outcomes in Patients with Head and Neck or Brain Tumors Undergoing Radiotherapy.

This cross-sectional study aimed to investigate the role of bioelectrical impedance analysis (BIA) and phase angle measurement in assessing malnutrition in head and neck (n = 37) and brain (n = 63) tumor patients received radiotherapy. Common nutritional screening and assessment tests were used to identify malnutrition in the patients. Each patient underwent these tests once, along with phase angle measurement. Additionally, inflammation parameters, including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and systemic inflammatory index (SII), were calculated. All study results were correlated with the phase angle cutoff point of 5.72°. The phase angle demonstrated significant correlations with subjective global assessment (SGA), mini nutritional assessment (MNA) scores, BIA parameters, nutritional index, NLR, and SII (p < 0.05). Moreover, in head and neck tumor patients, those with higher standardized phase angle values exhibited significantly better two-year overall survival (32.1% vs. 87.5%, p = 0.006). The phase angle measurement is a convenient, noninvasive, and reproducible method that can complement existing tools for assessing malnutrition risk in radiotherapy patients. The significant correlations observed between the phase angle and various nutritional, inflammation markers and prognosis highlight its potential utility. Further studies incorporating a larger patient cohort will be beneficial in establishing a standard phase angle reference value for cancer patients.

Radiation pneumonitis in relation to pulmonary function, dosimetric factors, TGFB1 expression, and quality of life in breast cancer patients receiving post-operative radiotherapy: a prospective 6-month follow-up study

Purpose To investigate development of radiation pneumonitis (RP) in relation to pulmonary function, dosimetric factors, and transforming growth factor beta-1 (TGFβ1) expression in irradiated breast cancer patients. Methods A total of 49 breast cancer patients who received post-operative radiotherapy (RT) were evaluated in terms of pulmonary function tests (PFTs), quality of life (QoL), development of RP, dosimetric factors, cytokine levels, and lung high-resolution computed tomography (HRCT) before and after RT. ROC analysis was performed for performance of dosimetric factors in predicting RP, while frequencies of single nucleotide polymorphisms (SNPs) genotyped for TGFβ1 (rs11466345 and rs1800470) were also evaluated. Results All cases with RP (10.2%) recovered clinically at the end of third post-RT month. PFT and HRCT parameters were similar before and after RT overall, as well as by RP and the radiation field subgroups. ROC analysis revealed the significant role of the ipsilateral V5 (cutoff value of 45.9%, p = 0.039), V10 (29.4%, p = 0.015), V20 (23%, p = 0.017), and MLD (1200 cGy, p = 0.030) in predicting RP. Higher post-RT TGFβ1 levels (p = 0.037) were noted overall and in patients with RP. Patient and control groups were similar in terms of frequencies of SNPs genotyped for TGFβ1 (rs11466345 and rs1800470). EORTC QLQ-C30 and QLQ-BR-23 scores were similar in patients with vs. without RP. Conclusion Our findings revealed significant role of dosimetric factors including MLD, V20 as well as the low dose-volume metrics in predicting the risk of RP among breast cancer patients who received post-operative RT. Implementation of RT, extent of radiation field or the presence of RP had no significant impact on PFTs (AU)

A multicenter retrospective analysis of patients with nasopharyngeal carcinoma treated in IMRT era from a nonendemic population: Turkish Society for Radiation Oncology Head and Neck Cancer Group Study (TROD 01-001).

BACKGROUND: We aimed to evaluate patients with nasopharyngeal carcinoma (NPC) in a nonendemic population. METHODS: In a national, retrospective, multicenteric study, 563 patients treated with intensity modulated radiotherapy at 22 centers between 2015 and 2020 were analyzed. RESULTS: Median age was 48 (9-83), age distribution was bimodal, 74.1% were male, and 78.7% were stage III-IVA. Keratinizing and undifferentiated carcinoma rates were 3.9% and 81.2%. Patients were treated with concomitant chemoradiotherapy (48.9%), or radiotherapy combined with induction chemotherapy (25%) or adjuvant chemotherapy (19.5%). After 34 (6-78) months follow-up, 8.2% locoregional and 8% distant relapse were observed. Three-year overall survival was 89.5% and was lower in patients with age ≥50, male sex, keratinizing histology, T4, N3 and advanced stage (III-IVA). CONCLUSIONS: Patients with NPC in Turkey have mixed clinical features of both east and west. Survival outcomes are comparable to other reported series; however, the rate of distant metastases seems to be lower.

Radiation pneumonitis in relation to pulmonary function, dosimetric factors, TGFß1 expression, and quality of life in breast cancer patients receiving post-operative radiotherapy: a prospective 6-month follow-up study.

PURPOSE: To investigate development of radiation pneumonitis (RP) in relation to pulmonary function, dosimetric factors, and transforming growth factor beta-1 (TGFß1) expression in irradiated breast cancer patients. METHODS: A total of 49 breast cancer patients who received post-operative radiotherapy (RT) were evaluated in terms of pulmonary function tests (PFTs), quality of life (QoL), development of RP, dosimetric factors, cytokine levels, and lung high-resolution computed tomography (HRCT) before and after RT. ROC analysis was performed for performance of dosimetric factors in predicting RP, while frequencies of single nucleotide polymorphisms (SNPs) genotyped for TGFß1 (rs11466345 and rs1800470) were also evaluated. RESULTS: All cases with RP (10.2%) recovered clinically at the end of third post-RT month. PFT and HRCT parameters were similar before and after RT overall, as well as by RP and the radiation field subgroups. ROC analysis revealed the significant role of the ipsilateral V5 (cutoff value of 45.9%, p = 0.039), V10 (29.4%, p = 0.015), V20 (23%, p = 0.017), and MLD (1200 cGy, p = 0.030) in predicting RP. Higher post-RT TGFß1 levels (p = 0.037) were noted overall and in patients with RP. Patient and control groups were similar in terms of frequencies of SNPs genotyped for TGFß1 (rs11466345 and rs1800470). EORTC QLQ-C30 and QLQ-BR-23 scores were similar in patients with vs. without RP. CONCLUSION: Our findings revealed significant role of dosimetric factors including MLD, V20 as well as the low dose-volume metrics in predicting the risk of RP among breast cancer patients who received post-operative RT. Implementation of RT, extent of radiation field or the presence of RP had no significant impact on PFTs.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Translation, validity, and reliability of NUTRISCORE: The nutrition risk assessment screening test for Turkish cancer patients.

PURPOSE: The aim was to determine the validity and the reliability of the Turkish version of the screening test named NUTRISCORE in cancer patients. METHODS: The language validity of the Turkish form of the study scale was provided by the translationback-translation method. NUTRISCORE and nutritional risk screening (NRS)-2002, malnutrition screening tool (MST), and European Diagnostic Criteria (EDC) were administered to 240 volunteers in oncology clinics, and receiver operating characteristic curves (ROC) were calculated for the validity and reliability analysis. Cohen's kappa coefficient was used to determine the fit between the screening tests. RESULTS: Thirteen experts were consulted for scale content validity, and the content validity index was found to be 0.94. The scale was administered to 67 patients with 4-week intervals for test-retest reliability, and a positive, high-level and statistically significant relationship was found between the two measurements (r = 0.971, P < 0.01). Compared with the reference test NRS-2002, the specificity values of NUTRISCORE, MST, and EDC screening tests were found to be 100%, 83%, and 91%, whereas the sensitivity values of same screening tests were calculated as 85%, 91% and 81%, respectively. According to Cohen's kappa statistics, the kappa agreement between NRS-2002 and NUTRISCORE was 0.88, the kappa agreement between NRS-2002 and MST was 0.34, and it was found to be 0.73 for NRS-2002 and EDC. CONCLUSION: The nutrition screening test named NUTRISCORE showed adequate validity and reliability in Turkish and can detect malnutrition risk of cancer patients treated in oncology clinics as a screening tool.

Impact of prognostic nutritional index on survival in recurrent glioblastoma.

BACKGROUND: Primary brain tumors are relatively rare malignancy, with high-grade gliomas (glioblastoma multiforme and anaplastic gliomas) are the most common types. We aimed to evaluate the prognostic value of Prognostic Nutritional Index (PNI), which is calculated by lymphocyte count and albumin, in recurrent glioblastoma patients treated with systemic treatment. METHODS: Data of 64 patients with recurrent glioblastoma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. PNI was calculated as: [(10×serum albumin (g/dL))+(0.005×total lymphocyte count)]. Patients were categorized according to the median PNI value. We investigated the prognostic role of PNI groups, and survival outcomes. RESULTS: Median value of PNI was 45.7, and median follow-up duration was 9 months (1-68 months). Median overall survival (OS) was 7.9 months (95%CI: 5.5-10.4). Median OS was significantly longer in patients with PNI>45.7 compared to patients with PNI≤45.7 (13.9 months (95%CI: 10.5-17.4), and 4.6 months (95%CI: 2.5-6.8), p<0.001, respectively). In multivariate analysis, PNI was found to be an independent prognostic factor for OS [HR:0.41 (95%CI:0.22-0.74), p=0.03)]. CONCLUSION: In our study, the PNI was found to be an independent prognostic biomarker in patients with recurrent glioblastoma, but further prospective trials are necessary to validate its prognostic role.

Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience.

PURPOSE: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor, and the prognosis is generally extremely poor. In this retrospective study, we analyzed the outcome of systemic treatment in recurrent high-grade glioma patients and the impact of prognostic factors on survivals. METHODS: Data from 114 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 were retrospectively analyzed. Eastern Cooperative Oncology Group (ECOG) performance status, age, gender, histology, type of surgical resection, side effects after systemic treatment (deep vein thrombosis, hypertension, proteinuria), IDH1 and alpha thalassemia/mental retardation syndrome X-linked (ATRX) mutation status were investigated as prognostic factors for progression-free survival and overall survival. RESULTS: At the time of diagnosis, the median age was 48 (17-77) and 68% of the patients were male. Most common pathologic subtype was glioblastoma multiforme (68%). Median follow-up duration was 9.1 months (1-68 months). Median progression-free survival and overall survival were 6.2 months and 8 months, respectively. In multivariate analysis, ECOG PS, deep venous thrombosis and the presence of ATRX and IDH1 mutation were found to be independent prognostic factors for progression-free survival (p < 0.05) and, ECOG PS, the presence of ATRX and IDH1 mutation for overall survival (p < 0.05). CONCLUSION: Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.

Rechallenge with dabrafenib plus trametinib in anaplastic thyroid cancer: A case report and review of literature.

INTRODUCTION: Anaplastic thyroid carcinoma (ATC) is a highly aggressive, undifferentiated rare tumor. Median overall survival is usually between 8 and10 months, with a 1-year survival rate of 20%. Conventional anthracycline based chemotherapy regimens demonstrate low response rates with short duration. Novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape of ATC have been investigated. CASE PRESENTATION: We herein report the rechallenge of a 52-year-old ATC patient with BRAF V600E mutation with dabrafenib plus trametinib. She presented with recurrent and progressive disease despite surgery, radiation therapy, 3 different chemotherapy regimens, and combination of dabrafenib-trametinib in different settings. She was rechallenged with dabrafenib-trametinib, and had a good response. CONCLUSION: To our knowledge, this is the first ATC case who responded to dabrafenib-trametinib rechallenge, reported in the literature. We want to emphasize that combination of dabrafenib and trametinib might be a good choice for resistant locoregional and metastatic ATC patients with BRAF V600E mutation, particularly in whom rapid clinical response is urgently needed. Moreover, rechallenge with this combination should be kept in mind in selected cases.

Prognostic value of modified Glasgow prognostic score in recurrent high-grade glial tumors treated with systemic treatment.

OBJECTIVES: Malignant high-grade gliomas are the most common and aggressive type of primary brain tumor. We aimed to evaluate the prognostic value of modified Glasgow Prognostic Score (mGPS), which is combination of C-reactive protein (CRP) and albumin, in recurrent high-grade glioma patients treated with systemic treatment. PATIENTS AND METHODS: Data of 85 patients with recurrent high-grade glioma who received systemic treatment and followed in our clinic between 2012 and 2018 was retrospectively collected and analyzed. Patients were grouped according to mGPS criteria: mGPS-0: CRP < 10 mg/L and albumin >3.5 g/dL; mGPS-1: CRP < 10 mg/L and albumin <3.5 g/dL or CRP > 10 mg/L and albumin >3.5 g/dL; and mGPS-2: CRP > 10 mg/L and albumin <3.5 mg/L. We investigated the prognostic role of mGPS groups, mutations and survival outcomes. RESULTS: There were 42 (49.4 %), 25 (29.6 %), and 18 (21 %) patients in mGPS-0, mGPS-1, and mGPS-2 groups, respectively. Median follow-up duration was 10 months (1-70 months). Median OS was 8.1 months. According to mGPS-0, -1 and -2; median OS was 13.8 months, 7.3 months and 3.6 months respectively (p = 0.003). mGPS, ATRX and IDH-1 mutation status, and ECOG PS were found to be independent prognostic factors for OS. CONCLUSION: In our study, mGPS was found to be an independent prognostic factor in patients with recurrent high-grade gliomas. If validated, mGPS can be used as an objective, easily calculated, cheap, and readily available prognostic model in routine practice.

Long-term neuromusculoskeletal side effects and quality of life in nasopharyngeal cancer patients receiving radiochemotherapy.

AIM: In this study, we aimed to evaluate the neuromusculoskeletal late side effects and their impact on the quality of life of patients with nasopharyngeal carcinoma treated with radiochemotherapy. PATIENTS AND METHODS: Twenty-seven patients were included. The mean follow-up was 61 months (range, 18-111 months). The median external radiotherapy dose applied to the nasopharynx and primary tumor was 70 Gy (range, 61-73 Gy). The mean dose received by the temporomandibular joint in the dose-volume histograms of these patients was 60.7 Gy. The maximal doses of the muscles responsible for cervical motion in different ranges were greater than 60 Gy, and the mean doses were greater than 40 Gy in the muscle groups, except for the extensor muscles. RESULTS: Two patients had brachial plexus involvement, while 89% of the patients had restriction in flexion and extension movements. Of the patients, 52% had trismus. There was a significant correlation between extension restriction and general heath score and the physical subscale of the quality-of-life questionnaire (p = 0.01). There was also a correlation between trismus and pain killer usage (p = 0.004). CONCLUSION: This is the first study to analyze long-term muscle and nerve toxicity and their correlation between doses in nasopharyngeal cancer patients following radiochemotherapy. Despite the advances in radiotherapy techniques, it is necessary to pay attention to the doses of the nerves and muscles for late effects.

Comparison of Three Nutritional Screening Tools to Predict Malnutrition Risk and Detect Distinctions Between Tools in Cancer Patients Receiving Radiochemotherapy.

The aim of this study was to compare three screening tools for malnutrition in patients with head and neck cancers or central nervous system tumors (CNS) who are undergoing radiochemotherapy. The study evaluated 124 adult cancer patients. The Subjective Global Assessment (SGA), Mini-Nutritional Assessment (MNA), and Nutritional Risk Screening 2002 (NRS-2002) were chosen to assess the risk of malnutrition. The prevalence of patients at nutritional risk was 31% with SGA, 31% with MNA and 23% with NRS-2002 in all patients. The agreement between SGA and MNA was substantial (κ = 0.886, P < 0.001); the agreement between SGA and NRS-2002 was moderate (κ = 0.713, P < 0.001); and the agreement between MNA and NRS-2002 was also moderate (κ = 0.795, P < 0.001). In subgroup analysis, SGA and MNA substantially (κ = 0.973, P < 0.001), SGA and NRS-2002 moderately (κ = 0.722, P < 0.001), and MNA and NRS-2002 moderately (κ = 0.747, P < 0.001) agreed in head and neck cancer patients. In CNS tumor patients, SGA and MNA slightly (κ = 0.390, P = 0.005), SGA and NRS-2002 fairly (κ = 0.457, P =0.001), and MNA and NRS-2002 substantially (κ = 0.878, P < 0.001) agreed. The best agreement in tools was observed between SGA with MNA in all patients. Further studies in different tumor groups will enhance our understanding of current tools for malnutrition detection of radiotherapy patient.

Resveratrol treatment may preserve the erectile function after radiotherapy by restoring antioxidant defence mechanisms, SIRT1 and NOS protein expressions.

Radiotherapy (RT) for prostate cancer (PC) can cause erectile dysfunction (ED) by damaging neurovascular structures with oxidative stress. In this study, we evaluated the effects of resveratrol, an antioxidant, on post-RT ED. Fifty rats in five groups were evaluated; control (C), prostate-confined radiotherapy with short- and long-term vehicle or resveratrol treatment. Cavernosal tissues were obtained to analyze glutathione (GSH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), 8-hydroxy-2'-deoxy-guanosine (8-OHdG) levels and superoxide dismutase (SOD), caspase-3 activities, sirtuin-1, Foxo-3, nNOS, and eNOS protein expressions. Intracavernosal pressures (ICP) were measured for the long-term treatment group. In the RT + long-term vehicle treatment group, tissue GSH, NO, cGMP, and SOD activity were decreased while 8-OHdg levels and caspase-3 activities were increased. Radiotherapy caused a decrease in sirtuin-1, nNOS, and eNOS protein expressions. These parameters were reversed by resveratrol treatment. Foxo-3 protein expressions were unaltered in the RT + short-term vehicle treatment group and started to increase as a defense mechanism in the RT + long-term vehicle group; however, resveratrol treatment caused a significant increase in Foxo-3 expressions. Resveratrol preserved the metabolic pathways involved in erectile function and provided functional protection. Resveratrol can be used as a supplementary agent in patients undergoing radiotherapy to preserve erectile function.

Early effects of irradiation on laryngeal mucosa in a gastroesophageal reflux model: an experimental study.

OBJECTIVE: The aim of this study was to evaluate the early histopathological changes of gastroesophageal reflux and irradiation on laryngeal mucosa in rats. STUDY DESIGN: Animal study. SETTING: Experimental animal laboratory, tertiary referral center. SUBJECT AND METHOD: Twenty-four adult female Wistar Albino rats were grouped as: control (n = 6), reflux and irradiation (n = 10), and irradiation (n = 8). Rats were operated to create a reflux model 30 days before irradiation. Ionizing radiation was administered in a single fraction of a 20 Gy to the larynx. Laryngeal tissue samples were taken at the 4th day of irradiation and all specimens underwent histopathological examination. RESULTS: Edema and vascular dilation in lamina propria were higher in the reflux and irradiation, and irradiation groups than control group. Inflammation was higher in the reflux and irradiation group than the control group. Inflammation in squamous epithelium was higher in the reflux and irradiation and irradiation groups compared to the control group. Inflammation in the squamous epithelium of the irradiation group was higher than the reflux and irradiation group. In the respiratory tract epithelium, inflammation was higher in the reflux and irradiation group; additionally, a significant loss of cilia was present in the reflux and irradiation and irradiation groups while pseudostratification was higher in the reflux and irradiation group. CONCLUSION: Ionizing radiation-induced inflammation may increase on previously inflammated area due to gastroesophageal reflux. Therefore, it may be helpful to investigate and treat the reflux in laryngeal cancer patients that will receive ionizing radiation.

A Diet Containing Beta-Hydroxy-Beta-Methylbutyrate, L-Glutamine and L-Arginine Ameliorates Chemoradiation-Induced Gastrointestinal Injury in Rats.

The aim of this study was to investigate the effects of a specific diet, containing beta-hydroxy-beta-methylbutyrate, L-glutamine and L-arginine (HMB/Glu/Arg), on chemoradiation-induced injuries of the rat gastrointestinal mucosa. Wistar albino rats were divided into 4 groups: control (n = 5); radiation (n = 14); 5-fluorouracil treatment (5-FU; n = 14); and radiation and 5-FU treatment (n = 14). Rats were fed either a standard diet or a specific diet (SpD) containing HMB/Glu/Arg supplementation for 7 days prior to radiation exposure and/or 5-FU treatment. The irradiated groups were exposed to an 1 Gy dose of 6 MV x rays delivered to the who-abdominal. The animals receiving 5-FU treatment were given a 100 mg/kg dose of the drug. In the radiation and 5-FU treatment group, the 5-FU was administered 30 min prior to irradiation. After irradiation and/or 5-FU treatment, feeding with either the standard rat diet or specific diet continued as before. All animals were sacrificed on day 4 after irradiation and 5-FU treatment. Data collected included microbiological, histological and immunohistochemical end points. We found that bacterial colony counts in the ceca and mesenteric lymph nodes of irradiated rats treated with 5-FU were significantly lower in the specific diet (SpD) group than in the standard diet group (P = 0.002-0.05). Morphometrically, gastric, duodenal and colonic mucosal injuries were less severe in the irradiated animals fed the specific diet, as well as the 5-FU-treated animals fed the specific diet, compared to the similarly treated standard diet groups. Apoptosis, measured by TUNEL, revealed significantly lower numbers of TUNEL positive cells in irradiated animals fed the specific diet, and irradiated animals treated with 5-FU and fed the specific diet compared to irradiated animals fed the standard diet, and irradiated animals treated with 5-FU and fed the standard diet. In the 5-Fu-treated and SpD group, the extent of apoptosis was significantly lower than that of the 5-Fu-treated and standard diet group in both the stomach and duodenum (P = 0.0001), but not in the colon. Apoptosis, measured by caspase 3 staining, was significantly less in all three organs of the SpD groups. In conclusion, these findings suggest that a diet supplemented with HMB/Glu/Arg may ameliorate the effect of radiation-induced gastrointestinal injury, coinciding with reduced bacterial growth.

Long-term effects of neoadjuvant chemoradiotherapy followed by sphincter-preserving resection on anal sphincter function in relation to quality of life among locally advanced rectal cancer patients: a cross-sectional analysis.

BACKGROUND: There is growing recognition for the consequences of rectal cancer treatment to maintain an adequate functional sphincter in the long-term rather than preserving the anal sphincter itself. This study aims to evaluate long-term effects of neoadjuvant chemoradiotherapy (nCRT) followed by sphincter-preserving resection on anal sphincter function in relation to quality of life (QoL) among locally advanced rectal cancer patients. METHODS: Twenty-nine patients treated with nCRT followed by low anterior resection surgery were included in this study. Data on patient demographics, tumor location and symptoms of urgency and fecal soiling were recorded and evaluated with respect to Wexner Fecal Incontinence Scoring Scale, European Organization for Research and Cancer (EORTC) cancer-specific (EORTC QLQ-C30) and colorectal cancer-specific (EORTC QLQ-CR38) questionnaires and anorectal manometrical findings. Correlation of manometrical findings with Wexner Scale, EORTC QLQ-CR38 scores and EORTC QLQ-C30 scores was also evaluated. RESULTS: Median follow-up was 45.6 months (ranged 7.5-98 months. Higher scores for incontinence for gas (p = 0.001), liquid (p = 0.048) and solid (p = 0.019) stool, need to wear pad (p = 0.001) and alteration in life style (p = 0.004) in Wexner scale, while lower scores for future perspective (p = 0.010) and higher scores for defecation problems (p = 0.001) in EORTC QLQ-CR38 were noted in patients with than without urgency. Manometrical findings of resting pressure (mmHg) was positively correlated with body image (r = 0.435, p = 0.030) and sexual functioning (r = 0.479, p = 0.011) items of functional scale, while rectal sensory threshold (RST) volume (mL) was positively correlated with defecation problems (r = 0.424, p = 0.031) items of symptom scale in EORTC QLQ-CR38 and negatively correlated with social function domain (r = -0.479, p = 0.024) in EORTC QLQ-C30. RST volume was also positively correlated with Wexner scores including incontinence for liquid stool (r = 0.459, p = 0.024), need to wear pad (r = 0.466, p = 0.022) and alteration in lifestyle (r = 0.425, p = 0.038). CONCLUSION: The high risk of developing functional anal impairment as well as the systematic registration of not only oncological but also functional and QoL related outcomes seem important in rectal cancer patients in the long-term disease follow-up.

Effects of testosterone treatment on recovery of rat spermatogenesis after irradiation.

OBJECTIVE: To determine the effects of two different radiation doses on sperm parameters and the role of testosterone treatment on rat spermatogenesis. METHODS: The experimental animal study was conducted at Marmara University, Istanbul, Turkey, from September 2012 to January 2013. Male Sprague Dawley 4-6 months old rats weighing 300-350g were randomely divided into 5 equal groups as control, low dose irradiation, testosterone administration following low dose irradiation, high dose irradiation, and testosterone administration following high dose irradiation. The animals were kept at a constant temperature in a room with 12h light and dark cycles. After the group-wise intervention, sperm concentration, testicular size, and histopathological examination of seminiferous tubules were noted. SPSS 10 was used for statistical analysis. RESULTS: The 40 rats in the study were divided in 5 groups of 8(20%) each. In low dose radiation, adverse effects were only temporarily observed with the return of almost normal testicular function at the end of two months with or without testosterone supplementation. In contrast, in high dose radiation, hormonal treatment effect was controversial. CONCLUSIONS: Testosterone treatment had no significant effect upon recovery after irradiation. In order to prevent the untoward effects of radiation, shielding of the remaining testis in a proper manner is crucial to avoid the harmful effects of the scattered radiation.

V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck.

INTRODUCTION: The purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors. METHODS: Thyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10-50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity. RESULTS: There were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors. CONCLUSIONS: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient's treatment.