Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Variations in Toll-like receptor and nuclear factor-kappa B genes and the risk of glioma.

PURPOSE: Glioblastoma (GBM) is the most aggressive primary brain tumour in the adult nervous system and is associated with a poor prognosis. NF-KB activation is an important driver of the malignant phenotype that confers a negative prognosis in patients with GBM. NF-KB plays a role in Toll-like Receptors (TLR)-induced tumourigenesis. The aim of the present study was to investigate the association of a promoter region polymorphism of NFKB1 gene encoding the p50 subunit of NF-KB, namely -94ins/del ATTG, the most widely discussed the TLR2 Arg753Gln, TLR4Asp299Gly and TLR4Thr399Ile polymorphisms, their combined effects, and the glioma risk. METHODS: A group of 120 Glioma patients and 225 control subjects were screened for these four polymorphisms using the PCR-RFLP method. RESULTS: Statistical analysis indicates that the ins/ins genotype of NFKB -94ins/delATTG (p=0.003), and the AA genotype of TLR4Asp299Gly (p < 0.001) are risk factors for glioma and people carrying the ins allele have an approximately 1.47 times susceptibility risk of glioma whereas GG genotype of TLR2Arg753Gln seems to be protective against glioma (p = 0.002). Combined genotype analysis showed that del/ins-GG genotype of TLR2Arg753Gln-NFKB1, del/ins + GG genotype of TLR4Asp299Gly-NFKB1, del/ins-CC genotype of TLR4Thr399Ile-NFKB1 were risk factors for glioma development. CONCLUSION: NFKB1 -94ins/delATTG and TLR4Asp299Gly polymorphisms are associated with increased glioma cancer risk in a Turkish population.

Orexin/hypocretin receptor, Orx1, gene variants are associated with major depressive disorder.

Objective: Orexins (hypocretins) are neuropeptides expressed in hypothalamic neurons and have regulatory roles in feeding/drinking behaviours, endocrine functions and sleep/wakefulness state. Major depressive disorder (MDD) is a major mood disorder and neurotransmitter dysfunction in hypothalamic neurons may have roles in its formation. Hence, we conducted experiments to determine whether orexin receptor 1 and 2 (Orx1, Orx2) genes were associated with MDD development. Methods: Seventy-five MDD patients and 87 healthy controls were enrolled for the study. Genotyping was carried out with real-time polymerase chain reaction (RT-PCR). Hamilton Rating-Scale for Depression (HRSD) and Beck Depression Inventory (BDI) were utilized to evaluate depressive symptom severity. Results: A significant relation was found in genotype frequencies of Orx1 rs10914456 and rs2271933 variants between MDD patients and controls (p = .009, p = .006). Rs10914456 CC genotype increased MDD risk 3.57 times more than carrying other genotypes (p = .008, OR =3.57;95% CI: 1.39-9.14). However, no association was observed in Orx2 rs2653349 genotypes for MDD development (p > .05). Although statistically not significant, HRSD scores were diminished in MDD subjects carrying rs10914456 CC variants when compared with CT and TT variants (p = .069). Conclusion. This study suggests that, Orx1 rs10914456 and rs2271933 can be associated with MDD development. Hence, Orx1 rs10914456 variants may affect depressive symptom severity.

The effects of Internet-based exercise compared with supervised group exercise in people with type 2 diabetes: a randomized controlled study.

OBJECTIVES: To compare the effects of Internet-based exercise on glycaemic control, blood lipids, body composition, physical activity level, functional capacity, and quality of life with supervised group exercise in patients with type 2 diabetes. DESIGN: Single-blind, randomized controlled study. SETTING: A Faculty of Health Sciences. SUBJECTS: A total of 65 patients with type 2 diabetes (47 women, 18 men). INTERVENTION: Group A ( n = 22), control group - physical activity counselling once with a brochure. Group B ( n = 22), supervised group-based exercise, three days per week for eight weeks. Group C ( n = 21), Internet-based exercise following the same programme via a website. MAIN MEASURES: Primary outcomes - glycosylated haemoglobin, fasting blood glucose, high-density and low-density lipoprotein, triglyceride, and cholesterol. Secondary outcomes - waist and hip circumferences, body mass index, number of steps, six-minute walking test, and Euro-Quality of Life-5 Dimension. RESULTS: After treatment, glycaemic control (mean change for Group B; Group C; -0.80%, -0.91%, P = 0.003), waist circumference (-4.23 cm, 5.64 cm, P = 0.006), and quality of life (0.26, 0.15, P = 0.013) significantly improved in both training groups compared with the control group. Fasting blood glucose (-46.86 mg/dL, P = 0.009) and hip circumference (-2.7 cm, P = 0.011) were significantly decreased in Group B and total cholesterol (-16.4 mg/dL, P = 0.028), six-minute walking distance (30.5 m, P = 0.01), and number of steps (1258.05, P = 0.023) significantly improved in Group C compared with control group. Group B and Group C changed with equal magnitude. CONCLUSION: In type 2 diabetes, supervised group-based and Internet-based exercise can improve equally glycaemic control, waist circumference, and quality of life, and both are better than simply counselling.

Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease.

AIM: Peripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development. METHODS: In this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system. RESULTS: ADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P<.05). CONCLUSION: This is the first report of the relationship between PAD and ADAMTS7 expression and the effects of the rs1994016 and rs3825807 variants on PAD development. ADAMTS7 may be associated with PAD development.

Development and validation of the stigma scale for epilepsy in Turkey.

OBJECTIVE: Epilepsy is a chronic disease with an increased risk of stigma. The aim of this study was to investigate the efficacy of a scale developed by the authors to determine the level of stigma in Turkish patients with epilepsy and their relatives. METHODS: In this pilot study, two scales were developed, one consisting of 32 questions for the patients and one of 20 questions for the patients' relatives. Initially, a total of 30 patients with epilepsy and 30 relatives of the patients were included. The Cronbach's alpha coefficient was calculated in a reliability analysis of validity applying the scales to 302 patients and 201 relatives of the patients. The Pearson correlation coefficient was used for the reliability analysis of the test-retest. The t-test was used in paired series, and factor analysis was conducted. The correlation between the clinical and demographical data and the stigma scores was evaluated. RESULTS: The scales were applied to participants twice under the same conditions in one-week interval. In the test-retest analysis, the internal consistency of the scales was high and reliable. In the analysis of the patients, the Cronbach's alpha value of the scale was found to be 0.915. In the factor analysis, the questions were grouped into five factors including social isolation, discrimination, insufficiency, false beliefs, and stigma resistance. The factors with the highest contribution to the stigma level were social isolation and discrimination. In the stigma scores, a significant correlation was found between the age of the patient, frequency of seizures, education status, level of income, and the amount of antiepileptic drugs used. In the analysis of the patients' relatives, the Cronbach's alpha value of the scale was found to be 0.892. In the factor analysis, the questions were classified as discrimination, prejudgments, and false beliefs. The factor which most contributed to the stigma level was discrimination. A significant correlation was found in the stigma scores between sex, education status, marital status, and income distribution. CONCLUSION: According to our study results, it is clearly seen that both patients and their relatives suffer from epilepsy-associated stigma. Patients with epilepsy and their relatives are faced with discrimination in society, resulting in social isolation. We, therefore, believe that both patients and their relatives should be informed in detail about discrimination to overcome this challenge.

Hormonal effect on the relationship between migraine and female sexual dysfunction.

It is not a well-established finding in migraine that female sexual dysfunction (FSD) emerging as a natural course of disease, as a result of accompanying depression/anxiety, or an underlying endocrinological abnormality. Our aim is evaluating the relationship among frequency and severity of migraine, FSD, depression, anxiety, and related hormones in migrainous women. We examined 80 migrainous female and 62 controls cross sectionally. Beck Depression and Anxiety Inventories, Female Sexual Dysfunction Inventory, Migraine Disability Assessment Test, and hormonal analysis were done. Independent risk factors were identified by logistic regression analysis and cut-off values were measured with Receiver Operating Curve. FSD was not related to frequency or severity of migraine. Although depression and anxiety was related to arousal and lubrication, they had limited effect in FSD. There were correlations between prolactin (PRL), desire and lubrication, follicular-stimulating hormone FSH and orgasm, luteinizing hormone (LH), and pain. Also FSH-LH combination and PRL were found as independent factors for FSD. FSH-LH combination and PRL were found as independent factors which had effect on FSD in migraine. Our study is a precursor study about the effect of several hormones on FSD and migraine relationship. Hormonal effect on FSD in migraine will be clearer with future studies.

Urine heat shock protein 70 levels as a marker of urinary tract infection in children.

BACKGROUND: Heat shock proteins (HSPs) are a multi-family group of proteins which are upregulated by the cell in response to exposure to hazardous (stress) factors, including infectious agents, to prevent changes in protein structure. The aim of our study was to assess whether urine levels of the 70-kDa family of HSPs (HSP70s) increase in children with urinary tract infection (UTI) and to determine the optimal urine (u) HSP70 cut-off level to predict UTI in children. METHODS: Forty patients with symptomatic UTI (UTI group), 30 healthy children (control group), 21 asymptomatic patients with proven bacterial contamination in their urine culture (contamination group) and 30 patients with fever caused by other infections (non-UTI infection group) were enrolled in the study. Random urine samples were obtained for measurement of HSP70 and creatinine (Cr) from all groups. Urine was collected prior to the treatment of UTI at the time of presentation and after treatment. Urine HSP70 levels were measured by enzyme-linked immunosorbent analysis. A dimercaptosuccinic acid (DMSA) scan was performed at 5-7 days after presentation in UTI group to distinguish patients with acute pyelonephritis from those with cystitis; based on this scan, no patients had acute pyelonephritis. Patients were classified with pyelonephritis in the presence of all of the following signs: axillary fever of ≥39 °C, leukocytosis and positivity for C-reactive protein. RESULTS: The mean urine HSP70:Cr ratio (uHSP70/Cr) prior to treatment was significantly higher in the UTI group (449.86 ± 194.33 pg/mg) than in the control, contamination and non-UTI infection groups (39.93 ± 47.61, 32.43 ± 9.09 and 45.14 ± 19.76, respectively; p = 0.0001). Using a cut-off of 158 pg/mg uHSP70/Cr for the prediction of UTI, the sensitivity and specificity of the assay were 100 and 100 %, respectively (area under the time-concentration curve = 1). The uHSP70/Cr was highest in the patients with clinical pyelonephritis (p = 0.001). Mean uHSP70/Cr after treatment decreased to 60.68 ± 51.11 pg/mg in UTI group (p = 0 .0001). CONCLUSIONS: Our findings suggest that elevated uHSP70/Cr may be a useful biomarker for the prediction of UTI in children, with a high sensitivity and specificity, and that they may help to distinguish UTI from other infections as well as bacterial contamination of the urine.

Morphological Changes of Trichomonas vaginalis Treated by Ornidazole: An In-Vitro Study.

BACKGROUND: Nitroimidazoles, which are drugs that are used to effectively treat Trichomonas vaginalis, alter the structure of the T. vaginalis cell membrane, penetrate into its cytoplasm and nucleus and block cellular metabolism. In this study, we observed the morphological changes that occurred in T. vaginalis during in vitro exposure to 1.3 µg/mL of ornidazole at various time intervals ranging from 10 minutes to 10 hours. METHODS: Vaginal and urethral secretion samples from suspected T. vaginalis cases were inoculated into Cysteine Peptone Liver Maltose medium. In 18 sterile tubes, 9.5 mL of this solution were mixed with 0.5 mL of ornidazole. The periods of contact between ornidazole and T. vaginalis ranged from 10 minutes to 10 hours. RESULTS: The first change was vacuolization, which started in the 10th minute of exposure. The glycogen particles started to diminish in the 20th minute. CONCLUSIONS: During exposure to 1.3 mg/L of ornidazole, cell lysis began in the 30th minute and accelerated towards the 60th minute (p < 0.001). Cytoplasmic matrix integrity was impaired in the 60th minute (p < 0.001).

Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.

Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.

The Effects of Adjuvant Endocrine Treatment on Serum Leptin, Serum Adiponectin and Body Composition in Patients with Breast Cancer: The Izmir Oncology Group (IZOG) Study.

BACKGROUND: A limited number of studies have been conducted on the effects of hormonal therapy with tamoxifen (TMX) or aromatase inhibitors (AIs) on plasma levels of leptin and adiponectin, as well as body composition in breast cancer (BC) patients. Therefore, we aimed to analyze the relationship between adipocytokines and body composition as well as the effects of TMX and AIs on plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and body composition. METHODS: Patients were treated with either TMX or AI according to their menopausal status after adjuvant radiotherapy. Changes in body composition and serum leptin and adiponectin levels were evaluated. We recorded the type of hormonal therapy, BMI, waist/hip ratio (WHR), leptin and adiponectin levels at study entry, and after 6 and 12 months. RESULTS: From baseline to the 6- and 12-month follow-ups, there were statistically significant increases in WHR (p = 0.003), fat mass (p = 0.041), and serum leptin (p < 0.001) and adiponectin levels (p < 0.001). The changes in body composition and serum leptin and adiponectin levels were similar in TMX and AI groups. A statistically significant decrease was found in total body water and LAR (p < 0.001). Although weight and body fat percentage increased, such increases were not statistically significant. A positive correlation was found between baseline BMI and serum leptin levels. This correlation was maintained at 6 and 12 months. The negative correlation found between serum adiponectin levels at baseline and baseline BMI did not last throughout the study. CONCLUSION: In this study, increased leptin and adiponectin levels and a decreased LAR were found in both AI and TMX groups. These changes might have occurred through both mechanisms of hormonal therapy and body composition changes. Therefore, AIs and TMX may exert their protective effects for BC patients by decreasing LAR rather than affecting leptin or adiponectin alone.

Independent effect of fatigue on health-related quality of life in patients with idiopathic Parkinson's disease.

Nonmotor symptoms (NMS) of idiopathic Parkinson's disease (IPD), specifically fatigue, depression and sleep disturbances, are important contributors for worse quality of life and poor patient outcomes. The aim of this research is to determine the relationship between fatigue and other NMS and the independent effect of fatigue on health-related quality of life (HRQoL) in patients with IPD. 86 IPD patients and 85 healthy individuals were included in our study. Participants were evaluated by their answers to the Beck Depression Inventory, Fatigue Severity Scale, Epworth Sleepiness Scale and Parkinson's Disease Questionnaire-39. Hoehn-Yahr stage, disease duration, medications and demographical characteristics were also noted. ROC analysis was used to determine the cutoff point for HRQoL. Nonparametric Spearman correlation analysis was used for determining the relationship between variables. Independent factors which affect HRQoL were detected by multiple forward stepwise logistic regression analysis. NMS were associated with each other and with HRQoL when they act concomitantly (p < 0.001). Of these three frequent NMS, depression (p < 0.05) and fatigue (p < 0.001) had independent worsening effect on HRQoL, whereas sleep disturbances did not (p > 0.05). The stage of IPD and levodopa-entacapone treatment had independent effects on HRQoL too (p < 0.05). Fatigue was found as the most important factor which affects HRQoL among all investigated NMS. So, it is important to ask about fatigue in routine controls of IPD patients and try to treat it for improving life quality.

Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with cancer. Similarly, a study in a large series has shown that the newly defined derived NLR (dNLR; neutrophil/leukocyte-lymphocyte ratio) also has prognostic value. The present study retrospectively evaluates the prognostic significance of NLR and dNLR in breast cancer. METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 1,527 patients diagnosed with breast cancer at Izmir Katip Celebi University Ataturk Research and Training Hospital from January 2006 to December 2011. The cut-off values were determined by calculating the NLR and dNLR of the patients. RESULTS: The cut-off values were determined as 4 and 2 for NLR and dNLR, respectively. The association between NLR and dNLR assessed by Spearman's rank correlation analysis was 0.935 (P < 0.001). There was a significant difference regarding disease free survival (DFS) and overall survival (OS) in patients with NLR <4 and NLR ≥4 (respectively, P < 0.00, P < 0.001). Similarly, there was a significant difference regarding DFS and OS in patients with dNLR <2 and dNLR ≥2 (respectively, P < 0.001, P < 0.001). Furthermore, NLR and dNLR demonstrated a significant association with the American Joint Committee on Cancer (AJCC) staging (P < 0.001). Assessment using the Cox proportional multivariate model showed that high NLR, pN, pT, luminal A-like, luminal B-like (HER2 positive), basal-like, and AJCC staging are independent prognostic factors. DISCUSSION: NLR was shown to be better than dNLR in terms of predicting prognosis in patients with breast cancer. However, large prospective studies are required to further demonstrate the prognostic significance of these two values.

Pro198Leu polymorphism in the oxidative stress gene, glutathione peroxidase-1, is associated with a gender-specific risk for panic disorder.

OBJECTIVE: Panic disorder (PD) is an anxiety disorder characterized by sudden attacks of intense fear. Biochemical studies suggest that oxidative stress (OS) index is significantly higher in PD, and OS genes may participate in development of anxiety-like behavioral phenotypes. We aimed to investigate role of polymorphisms in OS gene, glutathione peroxidase-1 (GPX1), and DNA repair enzyme gene, 8-oxoguanine glycosylase-1 (OGG1), in PD patients. METHODS: GPX1 Pro198Leu (rs1050450) and OGG1 Ser326Cys (rs1052133) polymorphisms of 127 patients with PD and 151 disease-free controls were analyzed with real-time polymerase chain reaction. Severity of PD symptoms was assessed by Panic and Agoraphobia Scale (PAS). RESULTS: No significant relationship was found in genotype distributions of OGG1 Ser326Cys and GPX1 Pro198Leu polymorphisms between PD and control groups (p > 0.05). There was no significant relationship between OGG1 or GPX1 polymorphisms, and age of onset, agoraphobia, or PAS scores in PD group (p > 0.05). However, in GPX1 Pro198Leu polymorphism, C allele (Pro) was found to be more frequent in female subgroup of PD patients compared with that in males (p = 0.027). CONCLUSIONS: GPX1 Pro198Leu and OGG1 Ser326Cys polymorphisms were not associated with PD risk in Turkish patients. However, a gender-specific effect of GPX1 Pro198Leu C allele may be associated with PD development.

Comparison of first-line bevacizumab in combination with mFOLFOX6 or XELOX in metastatic colorectal cancer.

PURPOSE: Currently, there are several oxaliplatin combination regimens for first-line therapy of metastatic colorectal cancer (mCRC). In this study, we compared the survival outcomes of mCRC patients treated with bevacizumab in combination with either modified 5-FU/FA/oxaliplatin (mFOL- FOX6) or capecitabine/oxaliplatin (XELOX). METHODS: We designed a two-arm retrospective study of mCRC patients with adenocarcinoma of the colon or rectum who were treated with bevacizumab and either mFOLFOX6 or XELOX and who had complete clinical and treatment data. We analysed their therapeutic responses, adverse events, progression-free survival (PFS), and overall survival (OS), and then determined whether there were any statistically significant differences. RESULTS: A total of 131 patients (85 male; 65% and 46 female; 35%) were evaluated. Fifty-seven patients (43.5%) were treated with bevacizumab and mFOLFOX6 and 74 (56.5%) with bevacizumab and XELOX. The median PFS was 9.1 months (95% CI, 4.9-13.1) and 10 months (95% CI, 4.2-15.9) in the mFOLFOX6 and XELOX arms, respectively (p=0.610). The median OS was 29 months (95% CI, 21.6- 34.3) and 27.5 months (95% CI 20-38) in the mFOLFOX6 and XELOX arms (p=0.812), respectively. The most common reason for treatment withdrawal was disease progression (102 patients; 91%) and the most common grade 3-4 toxicity was neuropathy (≤14%). CONCLUSION: Our results show that XELOX is a safe and effective alternative to mFOLFOX6 when combined with bevacizumab as first-line treatment for mCRC patients.

Quality of life in colorectal cancer patients: an Izmir Oncology Group (IZOG) study.

PURPOSE: To investigate the variables of quality of life (QoL) among Turkish patients with colorectal cancer (CRC). METHODS: In this prospective study we investigated the QoL of Turkish CRC patients. Two hundred and twenty two patients with CRC were included. The sociodemographic form and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) were used. RESULTS: The study group consisted of 142 males (64%) and 80 females (36%). The mean patient age was 55.68±11.387 years. The majority of the patients (36.9%) had local disease while advanced-stage disease and locally advanced stage disease had 32.2% and 28.8% of the patients; respectively. The mean QoL score was moderate (62.81± 27.0). The most common complaints were fatigue, economic difficulties and constipation. Gender, education level and disease stage were associated with QoL. Physical, role and social functioning were more adversely affected in female patients. Compared to women, men had significantly more favorable global QoL (p=0.044). Some functional scales were worse in advanced disease compared to other stages.These outcomes were statistically significant in the functional scales of global health (p=0.007), physical (p=0.03), cognitive (p=0.01) and emotional function (p=0.007). Patients with advanced disease had worse outcomes in some symptoms (nausea, vomiting, dyspnea, loss of appetite and financial distress). CONCLUSIONS: Female gender and advanced disease were strongly associated with poorer QoL among Turkish CRC patients.

Uracil/tegafur as a possible salvage therapy in chemo-refractory colorectal cancer patients: a single institutional retrospective study.

AIM OF THE STUDY: Our aim was to determine the activity and toxicity of uracil/tegafur and leucovorin combination in metastatic colorectal cancer (mCRC) patients who have progressed with all currently active agents. MATERIAL AND METHODS: This study was a retrospective analysis of 50 mCRC patients who had previously failed to respond to all available chemotherapeutics and who received subsequent treatment with uracil/tegafur 250 mg/m(2) d1-5 in combination with leucovorin 90 mg/day, d1-5 followed by two days' rest. RESULTS: The median age of the patients was 60 years. Most of them (60%) were male. Bevacizumab was used in 65% and cetuximab in 55% of the patients. Thirty-nine patients (78%) were treated with uracil/tegafur in the fourth line setting. The median treatment duration was 4.2 months (range, 2-24 months). The objective response rate and the disease control rate were 4% and 34%, respectively. Median progression-free survival was 4.1 months (95% CI, 3.6-4.6 months) and overall survival was 6.6 months (95% CI, 4.5-8.6 months). Grade 3 or 4 toxicity was seen in 20% (n = 10) of the patients while 60% (n = 6) of them required dose reductions. CONCLUSIONS: This retrospective data show that uracil/tegafur may be considered in heavily pretreated mCRC patients because of its activity, lower toxicity, and feasibility.

The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the prognostic value of cell cycle proteins and p53 together with clinicopathologic features in non-metastatic resected colon cancer. METHODS: One hundred nine patients who were diagnosed with resected colon cancer between 2006 and 2011 were analyzed retrospectively. Immunohistochemical staining analyses were used to evaluate the expression of cyclins D1 and A, p53 and Ki-67 in tumor tissue. RESULTS: High cyclin D1 and cyclin A expression was more common in stage II than stage III tumors. Disease recurrence was more frequent in tumors with low cyclin D1 expression (P = 0.05). No significant association was observed between p53, Ki-67 or cyclin A expression and the risk of relapse and/or death. Multivariate analysis showed that the strongest predictor for a shorter disease-free survival period was extracapsular nodal invasion (ECNI). CONCLUSIONS: We were not able to establish a strong association between patient prognosis and cyclins D1 and A, p53 or Ki-67 expression. However, a negative correlation between cyclin D1 and cyclin A expression and disease stage as well as more frequent relapses in patients with low expression of cyclin D1 suggested that cyclins may be predictive for early relapse in non-metastatic colon cancer.

Prognostic evaluation of breast cancer patients with evident bone marrow metastasis.

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty-four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor-positive, multicentric, grade III, advanced-stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single-agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.

Mandible bone metastases secondary to pulmonary adenocarcinoma.

OBJECTIVE: Metastatic tumors of the mandible are rare and usually present clinically as growths. The prognosis of lung cancer patients with bone metastases is poor. CASE REPORT: This article shows a metastasis from adenocarcinoma of the lung affecting the mandible of a 75-year-old female patient where the metastatic lesion was detected before primary tumor. The patient were treated with radiation therapy with palliative and antalgic intent. But the patient died 8 weeks after the diagnosis. CONCLUSION: Radiation therapy was effective and well tolerated in the case. Bone metastases particularly mandible metastasis of lung cancer has poor prognosis. Palliative and supportive therapy may be firstly chose because of poor prognosis.