Investigation of Neuroprotective Effect of Shilajit Extract in Experimental Head Trauma Model Created in Rats.

AIM: To investigate the neuroprotective effect of shilajit extract in experimental head trauma. MATERIAL AND METHODS: Three groups of 33 Sprague Dawley Albino strain male rats were included in the study. Group 1 (n=11): trauma but not treated. Group 2 (n=11): trauma and treated with 0.5 mL / rat saline Group 3 (n=11): 150 mg / kg shilajit extract was administered intraperitoneally in the treatment of trauma. Following the head trauma, the indicated treatments were applied to the 2nd and 3rd groups at the first, twenty-four and forty-eighth hours. Brain tissues and blood samples were taken after the control animals were sacrificed at the 72nd hour in all groups after trauma. Sections prepared from cerebral cortex and ca1 region were examined with hematoxylin eosin and luxol fast blue staining. Total antioxidant capacity, total oxidant capacity and oxidative stress index were measured from blood samples taken after routine procedures. RESULTS: The number of red neurons and the severity of edema were significantly higher in both the cerebral cortex and the ca1 region in the group treated with trauma only and in the group administered saline after trauma compared to the group that received shilajit extract after trauma. The total antioxidant capacity increased significantly in blood samples taken only from the group treated with trauma and saline in post-trauma treatment compared to the group given post-traumatic shilajit extract, while shilajit extract given due to traumatic brain injury significantly decreased the total oxidant capacity and oxidative stress index values compared to the other groups. CONCLUSION: Shilajit extract has been shown to have a neuroprotective effect in the treatment of acute traumatic brain injury. Our study showed that shilajit may be a useful option in the treatment of secondary brain injury, in humans.

GLIM criteria as a valid tool for nutrition assessment and mortality prediction in treatment-naïve patients with cancer.

BACKGROUND: Clinical care of patients with cancer mostly focuses on medical management with less attention on disease-related malnutrition. The Global Leadership Initiative on Malnutrition (GLIM) released new criteria for diagnosing malnutrition, but the validation of these criteria in treatment-naïve patients with cancer is not well documented. This study aimed to investigate the application of the GLIM criteria in nutrition assessment and mortality prediction in treatment-naïve patients with cancer. METHODS: A total of 267 patients newly diagnosed with different types of cancer were enrolled. Nutrition status was assessed with the Patient-Generated Subjective Global Assessment (PG-SGA) at outpatient clinic admission during the data collection period. Furthermore, after the GLIM criteria publication, nutrition status was assessed retrospectively using the GLIM criteria in the same cohort to assess validity. The agreement between the tools was calculated using kappa statistics, and the association of malnutrition according to each tool and mortality was analyzed using logistic regression analysis. RESULTS: The mean age of the patients was 58.06 ± 12.6 years, and 42.7% were women. The prevalence of malnutrition was 60.3% with GLIM criteria and 53.6% with PG-SGA. Agreement between tools was moderate (κ = 0.483, P < 0.001). During a median follow-up period of 23.6 months, 99 deaths occurred. Both GLIM-defined and PG-SGA-defined malnutrition was independently associated with 2-year mortality after adjusting for age, sex, presence of comorbidities, and stage of cancer. CONCLUSIONS: Our findings support the validation of GLIM in diagnosing malnutrition and predicting 2-year mortality among treatment-naïve patients with cancer.

The frequency and predictors of persistent amenorrhea in premenopausal women with colorectal cancer who received adjuvant chemotherapy.

The purpose of this study was to identify the frequency of chemotherapy-induced amenorrhea and associated factors thereof in premenopausal female patients diagnosed with colon cancer. Premenopausal female patients under the age of 50 years who were diagnosed with stages I, II, and III colon cancer were included. A questionnaire surveying personal history including menarche, comorbidities, drugs, other clinical features, and menstrual history during and after completion of chemotherapy was filled by the patients during outpatient visits. Patients who received pelvic radiotherapy were excluded from the study. A total of 60 patients were included in the study. Eleven patients had been treated with surgery alone, and 49 patients had received adjuvant chemotherapy with either fluorouracil (5-FU) alone (n=22) or 5-FU+oxaliplatin (n=27). The frequency of persistent amenorrhea 1 year after receiving chemotherapy was 20% in the whole group, 18% in patients who had received adjuvant chemotherapy with 5-FU alone, and 22% in patients who had received chemotherapy with 5-FU+oxaliplatin. Frequency of persistent amenorrhea was 3.5% in patients under the age of 44 years and 42.8% in patients aged 44 years and older. Multivariate analysis showed that age of 44 years and older (hazard ratio: 29.3; 95% confidence interval: 2.8-309.2, P=0.005) and menarche age of 14 years and older (hazard ratio: 7.6; 95% confidence interval: 1.2-49, P=0.076) were significantly associated with increased risk of persistent amenorrhea. In this study, we found that the frequency of persistent amenorrhea was 20% in patients who received 5-FU monotherapy or oxaliplatin-based adjuvant chemotherapy protocols in colon cancer treatment. Older age and later menarche were the factors that increased the risk of persistent amenorrhea 1 year after chemotherapy.

Is serum survivin expression a predictive biomarker in locally advanced gastric cancer patients treated with neoadjuvant chemotherapy?

BACKGROUND: The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE: Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS: Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS: Median survivin level was 147 IU/L (range = 4.4-4936) at baseline and was 27 IU/L (range = 4.2-4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8-1430) and pre-treatment patient group was statistically significant (p< 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p= 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p< 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p= 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p= 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p= 0.14). CONCLUSION: It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results.

Results of adjuvant FOLFOX regimens in stage III colorectal cancer patients: retrospective analysis of 667 patients.

OBJECTIVE: The aim of this study was to assess the use of 5-fluorouracil (5-FU), leucovorin and oxaliplatin (FOLFOX) regimens in clinical practice according to their efficacy and toxicity. METHODS: Patients who received oxaliplatin-containing regimens after curative resection for colorectal carcinoma from 10 different oncology centers between May 2004 and December 2009 were included in the study. All patients were treated with FOLFOX regimens. Patients with rectal carcinoma were also treated with chemoradiotherapy with 5-FU after 2 cycles of a FOLFOX regimen. RESULTS: The median age of the patients was 56 years (range 17-78). Of the total 667 patients, 326 were given FOLFOX-4, 232 were given modified FOLFOX-4 and 109 were given FOLFOX-6. The distribution according to disease stage was 33 patients with stage IIIA colorectal cancer, 382 patients with stage IIIB and 252 patients with stage IIIC. The most common adverse events were neutropenia (54%), nausea (36.9%), neuropathy (38.2%) and anemia (33.1%) for all grades. The median follow-up time was 23 months (range 1-79). Three-year disease-free survival and overall survival were 65 and 85.7%, respectively. CONCLUSION: The different oxaliplatin-containing 5-FU-based adjuvant chemotherapy regimens in patients with stage III colorectal cancer seemed to be at least equal in terms of efficacy regardless of the method of 5-FU administration or oxaliplatin dose.

Efficiency and side effects of sorafenib therapy for advanced hepatocellular carcinoma: a retrospective study by the anatolian society of medical oncology.

BACKGROUND: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-ß) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. MATERIALS AND METHODS: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). RESULTS: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. CONCLUSIONS: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Adjuvant chemoradiation for gastric cancer: multicentric study of the Anatolian Society of Medical Oncology.

BACKGROUND/AIMS: The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer. METHODOLOGY: The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. RESULTS: Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS. CONCLUSIONS: Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.

Adjuvant modified FOLFOX-4 in patients with stage III rectum adenocarcinoma.

PURPOSE: The aim of this study was to investigate efficacy and toxicity of a modified 5-fluorouracil (5-FU), folinic acid, oxaliplatin (mFOLFOX-4) regimen followed by infusional 5-FU concomitant with radiotherapy for curatively resected stage III rectum adenocarcinoma patients. PATIENTS AND METHODS: Between April 2005 and July 2009, 55 operated stage III rectum cancer patients were evaluated retrospectively. mFOLFOX-4 regimen (oxaliplatin 85 mg/m2 1st day, folinic acid 200 mg/m2 1st day, 5-FU 400 mg/m2 iv bolus 1st day, 5-FU 1600 mg/m2 46 hours continuous infusion) was applied every 2 weeks. After four courses of mFOLFOX-4, 50.4 Gy (1.8 Gy in 28 fractions) radiotherapy with continuous 5-FU 200 mg/m(2)/day by infusion pump were given. On completion of chemoradiation four more mFOLFOX-4 courses were given. RESULTS: Median age of the patients was 54 years (range 23-73 years). Low anterior resection was performed in 37 (67.3%) and abdominoperineal resection in 16 (29.1%) . Ten (18.2%) patients were at stage IIIA, 24 (43.6%) at stage IIIB and 21 (38.2%) at stage IIIC. Planned chemotherapy cycles were completed in 92.7% of patients. Grades 3-4 toxicity included neutropenia (9.1%), febrile neutropenia (3.6%), anemia (3.6%), diarrhea (21.8%), neuropathy (9.1%), renal toxicity (3.6%), hepatotoxicity (5.5%). Median follow-up time was 30 (9-57) months. Local recurrence and distant metastasis was observed in 3 (5.5%) and 10 (18.2%) patients, respectively. Ten (18.2%) patients died during follow-up. Three years disease free survival and overall survival were 67.5% and 77.3%, respectively. CONCLUSION: mFOLFOX-4 following chemoradiotherapy with continuous 5- FU infusion is an effective and well tolerated adjuvant treatment for stage III rectal carcinoma patients.

Adjuvant bi-weekly combination of cisplatin, infusional 5-fluorouracil and folinic acid followed by concomitant chemoradiotherapy with infusional fluorouracil for high risk operated gastric and gastroesophageal junction adenocarcinoma.

PURPOSE: Chemotherapy and radiotherapy are approved in clinical practice of adjuvant treatment of gastric carcinoma. In present study, we retrospectively evaluated the efficacy and tolerability of an adjuvant treatment protocol including bi-weekly cisplatin, infusional 5-fluorouracil (5-FU) and folinic acid followed by continuous 5-FU infusion during radiotherapy. PATIENTS AND METHODS: Between May 2005 and Dec 2008, 65 curatively resected gastric and gastroesophageal junction adenocarcinoma patients (stage III in 38 and stage IV M0 in 27) received chemotherapy including 50 mg/m2 cisplatin, 200 mg/m2 iv folinic acid, 5-FU 400 mg/m2 iv bolus followed by 5-FU 1600 mg/m2 46h-continuous infusion (CFF) bi-weekly. After 4 cycles of CFF, concomitant 200 mg/m2/day continuous infusion 5-FU and 4500 cGy radiotherapy were administered for 5 weeks. After this chemoradiotherapy an additional 4 cycles of CFF were given. RESULTS: The median follow-up was 15 (6-36) months. Fifty seven (87.7%) patients completed at least 90% of the planned treatment. Median disease free survival was 18 months (95% CI:13.9-22.0) and median overall survival was 19 months (95% CI:15.2-22.8). Common adverse events of all grades were nausea and vomiting (53.8%), leucopenia (42.6%), anemia (30.7%) and diarrhea (20%). The most common grade 3 and 4 toxicities were leucopenia (9.2%), anemia (7.6%), febrile neutropenia (6.1%) and diarrhea (4.6%). CONCLUSION: Bi-weekly CFF chemotherapy followed by continuous 5-FU infusion during radiotherapy is an effective and tolerable regimen for locally advanced operated gastric and gastroesophageal junction adenocarcinoma.