Publications by authors named "Deniz Yuce"

52 Publications

Oxysterol species generated by auto-oxidation in subclinical hypothyroidism.

Clin Biochem 2021 Apr 20. Epub 2021 Apr 20.

Division of Endocrinology and Metabolism, Hacettepe University School of Medicine, Hacettepe, Ankara, Turkey; Department of Internal Medicine, Hacettepe University School of Medicine, Hacettepe, Ankara, Turkey.

Background: Auto-oxidized oxysterols are implicated in the pathogenesis of various chronic diseases. Their concentrations are indicators of oxidative stress in vivo and associated with atherosclerosis. Subclinical hypothyroidism is related with cardiac diseases and oxidative stress, but the exact mechanisms underlying these associations are not clear yet.

Objective: To investigate the auto-oxidized oxysterols, 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (chol-triol), in patients with subclinical hypothyroidism, as well as to evaluate the impact of restoring euthyroidism on oxysterol concentrations.

Methods: In this prospective observational study, 64 patients with newly diagnosed autoimmune thyroiditis (41 with subclinical hypothyroidism and 23 euthyroidism), and 45 healthy controls were enrolled. Age, gender, and body mass index were matched among patient groups and healthy controls. Anthropometric measurements were obtained and fasting plasma 7-ketocholesterol and cholestane-3β,5α,6β-triol concentrations were measured by using liquid chromatography coupled with tandem mass spectrometry. Levothyroxine was then administered to all patients with subclinical-hypothyroidism. After three months, measurements of the oxysterols and serum cholesterols from the patients who have become euthyroid were repeated.

Results: Concentrations of 7-ketocholesterol and cholestane-3β,5α,6β-triol were significantly higher in patients with subclinical-hypothyroidism when compared to both euthyroid patients and healthy controls (p < 0.001 for both oxysterols). After restoration of euthyroidism, concentrations of 7-ketocholesterol and cholestane-3β,5α,6β-triol decreased significantly and reached similar concentrations observed in healthy controls (p < 0.001 for both oxysterols).

Conclusions: Auto-oxidized oxysterol species are higher in patients with mild thyroid dysfunction, and supported the rationale for treating subclinical-hypothyroidism.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.04.007DOI Listing
April 2021

Impact of albumin to globulin ratio on survival outcomes of patients with metastatic renal cell carcinoma.

Turk J Urol 2021 Mar 1;47(2):113-119. Epub 2021 Mar 1.

Department of Preventive Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Objective: The albumin to globulin ratio (AGR) has been demonstrated to be associated with survival outcomes in various tumor types. However, the prognostic value of AGR in patients with metastatic renal carcinoma (mRCC) remains unclear. Therefore, this study aimed to investigate the impact of AGR values in predicting overall survival (OS) of patients with mRCC treated with targeted therapy.

Material And Methods: A total of 163 patients with mRCC treated with targeted therapy between 2008 and 2019 were enrolled. The AGR value was measured as AGR: albumin/(total protein-albumin). The Kaplan-Meier method with long-rank testing and Cox proportional hazard models were used to estimate the correlation of AGR with OS.

Results: The receiver operating characteristic curve analysis showed that the optimal cut-off value of AGR in predicting OS was 1.11 with a sensitivity of 37.25% and specificity of 85.25% (area under curve, 0.62; 95% confidence interval [CI], 0.54-0.69; p=0.005). OS was significantly higher in patients with AGR>1.11 than in those with AGR≤1.11 (36.2 vs. 12.4 months; p<0.001). After adjustment for the number of covariates, multivariate Cox regression analysis identified a high AGR as an independent indicator of better OS (hazard ratio, 0.476; 95% CI, 0.304-0.745; p=0.001).

Conclusion: Our results suggested that AGR value, which is an easily obtainable and cost-effective marker in routine biochemistry testing, could function as an independent predictor of OS in patients with mRCC treated with targeted therapy.
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http://dx.doi.org/10.5152/tud.2021.20377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018802PMC
March 2021

The Predictive Value of Red Blood Cell Distribution Width for Survival Outcomes of Metastatic Renal Cell Carcinoma Patients Treated with Targeted Therapy.

Nutr Cancer 2021 Jan 25:1-7. Epub 2021 Jan 25.

Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Background: We aimed to investigate the prognostic value of red cell distribution width (RDW) in metastatic renal cell carcinoma (mRCC) patients treated with targeted therapy, including sunitinib and pazopanib.

Methods: A total of 104 mRCC patients were included. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), and the long-rank test was used for comparison. Univariate and multivariate Cox proportional hazards models were used to determine the association between RDW and PFS and OS.

Results: The PFS and OS of all cohorts were 11.8 mo and 25.9 mo, respectively. Receiver operating characteristic analysis revealed that RDW level ≥15.4 was the optimal cutoff value for OS prediction with 73.53% sensitivity and 61.11% specificity (area under curve: 0.64,  = 0.012). RDW level ≥15.4 was found as an independent prognostic parameter for OS when adjusted for the number of covariates, including the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) scoring system (hazard ratio: 1.125, 95% confidence interval: 1.024-2.235,  = 0.014).

Conclusions: Our study revealed that high RDW level, a routinely and easily assessed marker, was significantly associated with worse survival outcomes in mRCC patients treated with targeted therapy.
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http://dx.doi.org/10.1080/01635581.2021.1871925DOI Listing
January 2021

Adjuvant vaginal cuff brachytherapy: dosimetric comparison of conventional versus 3-dimensional planning in endometrial cancer.

J Contemp Brachytherapy 2020 Dec 16;12(6):601-605. Epub 2020 Dec 16.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Purpose: To evaluate dosimetric differences between point-based 2-dimensional (2D) vaginal brachytherapy (VBT) treatment planning technique and volume-based 3-dimensional (3D) VBT method for endometrial cancer (EC).

Material And Methods: Ten patients with uterine-confined EC treated with VBT were included in this study. All patients received 27.5 Gy in 5 fractions. Three different treatment plans were performed for each patient: plan A for dose prescribed to the entire vaginal wall thickness delineated via computed tomography guidance, plan B for dose prescribed to the vaginal mucosa/cylinder surface, and plan C for dose prescribed to 5 mm beyond the vaginal mucosa/cylinder surface. Dose-volume histograms (DVH) of treatment volumes and organs at risk (OARs) were evaluated and compared.

Results: DVH analysis of target volume doses (D, D, and D) showed a significant difference between plan A and plan B ( = 0.005), and plan B was found lower. D for plan C was significantly higher than plan A ( = 0.009), but for D and D, no statistically significant difference was found ( = 0.028 and = 0.028, respectively). In terms of OARs doses, including vagina, rectum, bladder, and sigmoid, D doses were significantly higher in plan A than plan B ( = 0.009, = 0.009, = 0.005, and = 0.005, respectively). All these doses were also significantly lower than in plan C ( = 0.005, = 0.012, and = 0.013, respectively), except for sigmoid ( = 0.155).

Conclusions: In this dosimetric analysis, we have shown that the volume-based 3D VBT technique provides the ability to balance the target dose against the sparing of OARs. Therefore, in the new modern 3D treatment era, instead of normalization of the dose to standard reference points, customized 3D volume-based VBT planning should be recommended.
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http://dx.doi.org/10.5114/jcb.2020.101694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787204PMC
December 2020

The platelet to lymphocyte ratio predicts overall survival better than the neutrophil to lymphocyte ratio in metastatic renal cell carcinoma

Turk J Med Sci 2021 04 30;51(2):757-765. Epub 2021 Apr 30.

Department of Preventive Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Background/aim: The prognostic values of systemic inflammatory markers, neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) on overall survival (OS) of metastatic renal cell carcinoma patients (mRCC) treated with tyrosine kinase inhibitors (TKI) remain unclear. Thus, the present study aimed to investigate the prognostic impact of these markers on OS of mRCC patients.

Materials And Methods: A total of 150 patients receiving TKIs were retrospectively analyzed. Progression-free survival and OS times were analyzed with the Kaplan–Meier method, and the log‐rank test was used for comparison. Univariable and multivariable Cox regression models evaluated the impact of NLR and PLR on OS of the patients. The receiver operating characteristic curve analysis determined that the optimal cut-off values of NL, and PLR in predicting OS were 2 and 204, respectively.

Results: Patient with PLR > 204 had significantly lower median OS time than those with PLR ≤ 204 (14.6 months vs. 31.6 months, P < 0.001). While the univariate analyses showed that both NLR and PLR associated with OS (NLR: P = 0.002; PLR: P < 0.001), PLR, not NLR, was an independent determinant for OS in the multivariate analyses (Hazard Ratio: 2.535, 95% CI: 1.564-4.108, P < 0.001). Additionally, the presence of brain metastases and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic scoring system were identified as independent prognostic factors for OS (brain metastases: P = 0.040; IMDC: P < 0.001).

Conclusion: The PLR is a readily and inexpensively obtained marker, which may predict OS in patients with mRCC treated with TKIs.
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http://dx.doi.org/10.3906/sag-2009-75DOI Listing
April 2021

Parotid gland stem cells: Mini yet mighty.

Head Neck 2021 Apr 27;43(4):1122-1127. Epub 2020 Nov 27.

Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Background: Our aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia.

Methods: Patients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated.

Results: The total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002).

Conclusions: In this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.
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http://dx.doi.org/10.1002/hed.26556DOI Listing
April 2021

Left atrial mechanics for secondary prevention from embolic stroke of undetermined source.

Eur Heart J Cardiovasc Imaging 2020 Nov 18. Epub 2020 Nov 18.

Cardiology Department, University of Baskent, 54. sokak E blok No: 45 Bahcelievler, 06490 Ankara, Turkey.

Aims : Anticoagulation is not justified unless atrial fibrillation (AF) is detected in cryptogenic stroke (CS) patients. We sought to explore whether left atrial (LA) remodelling is associated with embolic stroke of undetermined source (ESUS).

Methods And Results : In this prospective study, we evaluated consecutively 186 patients in sinus rhythm who presented with an acute ischaemic stroke (embolic and non-embolic) and sex- and age-matched controls. We performed continuous electrocardiogram (ECG) monitoring to capture paroxysmal AF episodes as recommended by the guidelines. After 12 months of follow-up, continuous ECG monitoring was repeated in patients with undetected AF episodes. We quantified LA reservoir and contraction strain (LASr and LASct) by speckle-tracking, LA volumes by 3D echocardiography. Out of 186 patients, 149 were enrolled after comprehensive investigation for the source of ischaemic stroke and divided into other cause (OC) (n = 52) and CS (n = 97) groups. CS patients were also subdivided into AF (n = 39) and ESUS (n = 58) groups. Among CS patients, LA strain predicted AF independently from CHARGE-AF score and LA volume indices. ESUS group, despite no captured AF, had significantly worse LA metrics than OC and control groups. AF group had the worst LA metrics. Moreover, LASr predicted both CS (embolic stroke with and without AF) and ESUS (embolic stroke with no detected AF) independently from LAVImax and CHA2DS2-VASc score. LASr >26% yielded 86% sensitivity, 92% specificity, 92% positive, and 86% negative predictive values for the identification of ESUS (areas under curve: 0.915, P < 0.0001, 95% confidence interval: 0.86-0.97).

Conclusion : Echocardiographic quantification of LA remodelling has great potential for secondary prevention from ESUS.
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http://dx.doi.org/10.1093/ehjci/jeaa311DOI Listing
November 2020

The Bournemouth Questionnaire for Neck Pain: Cross-cultural Adaptation, Reliability, and Validity of the Turkish Version.

J Manipulative Physiol Ther 2020 09 4;43(7):708-713. Epub 2020 Sep 4.

Department of Occupational Therapy, Hacettepe University, Ankara, Turkey.

Objective: The aim of this study was first to translate and culturally adapt the BQN, and then to investigate the validity and reliability of the Turkish version of the BQN in Turkish individuals with chronic neck pain.

Methods: The English version of the BQN was translated into Turkish with permission from its authors. That translation was assessed using 85 participants with a mean age of 46.75 years who had chronic neck pain. At the same time, the participants were assessed sociodemographically and with the Neck Disability Index (NDI) and the Neck Pain and Disability Scale (NPAD). A test-retest procedure was performed with 62 participants who underwent a second assessment with the BQN within 24 hours of the first assessment, to test its reliability.

Results: Internal consistency was strong and all Cronbach alpha values were between 0.97 and 0.99. The BQN showed high test-retest reliability (intraclass correlation coefficient ˃ 0.92) for all domains. The total mean (± standard deviation) scores for the 3 questionnaires were as follows: BQN, 30.9 (± 11.18); NPAD, 48.16 (± 12.93); NDI, 17.85 (± 6.29). The results of the Turkish version of the BQN illustrated adequate external construct validity and sensitivity. A Turkish translation of the test has not previously been available for chronic pain.

Conclusion: The BQN was successfully translated and culturally adapted into Turkish. The reliability and validity were tested against the NPAD and the NDI. The Turkish version of the BQN is multidimensional, short, practical, and suitable for use with individuals with neck pain.
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http://dx.doi.org/10.1016/j.jmpt.2018.11.039DOI Listing
September 2020

Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus.

Turk Neurosurg 2020 ;30(6):871-884

Gazi University, School of Medicine, Department of Pharmacology, Ankara, Turkey.

Aim: To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE).

Material And Methods: Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups.

Results: All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2.

Conclusion: Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.
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http://dx.doi.org/10.5137/1019-5149.JTN.27023-19.3DOI Listing
April 2021

Stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer: Does beam-on time matter?

Jpn J Clin Oncol 2020 Sep;50(10):1182-1187

Radiation Oncology, Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey.

Purpose: Stereotactic body radiotherapy (SBRT) is an effective treatment option for patients with early-stage non-small cell lung cancer (NSCLC). In this study, we evaluated the treatment results using two different SBRT techniques and the effect of beam-on time (BOT) on treatment outcomes.

Methods: Between July 2007 and January 2018, 142 patients underwent SBRT for primary NSCLC. We have delivered SBRT using either respiratory tracking system (RTS) or internal-target-volume (ITV)-based motion management techniques. The effect of age, tumor size, pretreatment tumor SUVmax value, presence of tissue diagnosis, histopathological subtype, operability status, tumor location, motion management technique, BED10 value, BOT on overall survival (OS), loco-regional control (LRC), event-free survival (EFS) and primary tumor control (PTC) were evaluated.

Results: Median age of the patients was 70 years (range, 39-91 years). Most of the patients were inoperable (90%) at the time of SBRT. Median BED10 value was 112.5 Gy. With a median follow-up of 25 months, PTC was achieved in 91.5% of the patients. Two-year estimated OS, LRC, PTC and EFS rates were 68, 63, 63 and 53%, respectively. For the entire group, OS was associated with BOT (P = 0.027), and EFS was associated with BOT (P = 0.027) and tumor size (P = 0.015). For RTS group, OS was associated with age (P = 0.016), EFS with BOT (P = 0.05) and tumor size (P = 0.024), LRC with BOT (P = 0.008) and PTC with BOT (P = 0.028). The treatment was well tolerated in general.

Conclusion: SBRT is an effective and safe treatment with high OS, LRC, EFS and PTC rates in patients with primary NSCLC. Protracted BOT might deteriorate SBRT outcomes.
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http://dx.doi.org/10.1093/jjco/hyaa093DOI Listing
September 2020

Maternal plasma endocan levels in intrauterine growth restriction.

J Matern Fetal Neonatal Med 2020 Apr 14:1-6. Epub 2020 Apr 14.

Department of Perinatology, Zekai Tahir Burak Women's Research and Tertiary Hospital, Ankara, Turkey.

Intrauterine growth restriction (IUGR) is diagnosed when the estimated fetal weight remains below the 10th percentile of gestational age based on pathological restriction of growth and/or accompanying Doppler abnormalities. Endothelial dysfunction is a common pathogenetic pathway underlying IUGR etiology. Endocan (ESM-1) is a novel marker of endothelial dysfunction and inflammation found in the maternal circulation. This study was designed to compare plasma endocan levels between pregnancies complicated with IUGR and a control group. Forty-four pregnancies complicated with IUGR and 47 healthy pregnancies were included. Maternal plasma endocan levels were detected by ELISA. Parametric data was studied by Student's -test. Mann-Whitney -test was used in analyzing non-parametric data. Categorical variables underwent chi-square test. ROC analysis was performed to define the cutoff value of endocan in detecting IUGR. Spearman correlation test was performed. Maternal plasma endocan level varied significantly between IUGR and healthy pregnancies and was 1.8 fold higher in the IUGR group (793.0 (IQR:544.4-1896.0) ng/L vs. 441.8 (IQR: 408.3-512.4) ng/L,  < .001). There was a weak negative correlation between endocan level and 5th and 10th minute APGAR Scores ( =  -0.256;  = .015 and  =  -0.215;  = .042, respectively), a weak positive correlation with umbilical artery pulsatility index, and a moderate negative correlation with cerebroplacental ratio (  =  0.394;  < .001 and  =  -0.459;  < .001, respectively). There was a significant difference between endocan levels of IUGR and healthy pregnancies. Further studies might be designed to investigate the performance of endocan in predicting neonatal outcomes for pregnancies complicated with IUGR.
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http://dx.doi.org/10.1080/14767058.2020.1749591DOI Listing
April 2020

Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BMC Cancer 2020 Mar 30;20(1):259. Epub 2020 Mar 30.

Hacettepe University Cancer Institute, Ankara, Turkey.

Background: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown.

Methods: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL.

Results: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6 month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms.

Conclusions: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer.

Trial Registration: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).
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http://dx.doi.org/10.1186/s12885-020-06758-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106641PMC
March 2020

Prognostic significance of castrate testosterone levels for patients with intermediate and high risk prostate cancer.

World J Clin Oncol 2019 Aug;10(8):283-292

Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey M.D.

Background: Testosterone level of < 50 ng/dL has been used to define castrate level after surgery or after androgen deprivation treatment (ADT) in metastatic prostate cancer (PC).

Aim: To evaluate the effect of two different castrate testosterone levels, < 50 and < 20 ng/dL, on biochemical relapse free survival (BRFS) in patients with non-metastatic intermediate and high risk PC receiving definitive radiotherapy (RT) and ADT.

Methods: Between April 1998 and February 2011; 173 patients with intermediate and high risk disease were treated. Radiotherapy was delivered by either three-dimensional-conformal technique to a total dose of 73.4 Gy at the ICRU reference point or intensity modulated radiotherapy technique to a total dose of 76 Gy. All the patients received 3 mo of neoadjuvant ADT followed by RT and additional 6 mo of ADT. ASTRO Phoenix definition was used to define biochemical relapse.

Results: Median follow up duration was 125 months. Ninety-six patients (56%) had castrate testosterone level < 20 ng/dL and 139 patients (80%) had castrate testosterone level < 50 ng/dL. Both values are valid at predicting BRFS. However, patients with testosterone < 20 ng/dL have significantly better BRFS compared to other groups ( = 0.003). When we compare two values, it was found that using 20 ng/dL is better than 50 ng/dL in predicting the BRFS (AUC = 0.63 0.58, respectively).

Conclusion: Castrate testosterone level of less than 20 ng/dL is associated with better BRFS and is better in predicting the BRFS. Further studies using current standard of care of high dose IMRT and longer ADT duration might support these findings.
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http://dx.doi.org/10.5306/wjco.v10.i8.283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717705PMC
August 2019

Evaluation of cancer risk in patients with periodontal diseases

Turk J Med Sci 2019 06 18;49(3):826-831. Epub 2019 Jun 18.

Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey

Background/aim: In this study, we aimed to assess the cancer risk among patients with periodontal disease.

Materials And Methods: Patients diagnosed with periodontal diseases at Hacettepe University between 2007 and 2012 were included and data on the diagnosis of any cancer after periodontal disease were collected from patient files. The age- and sex-standardized incidence rates (SIRs) were calculated using Turkish National Cancer Registry 2013 data.

Results: A total of 5199 patients were included. Median follow-up was 7.2 years. Patients with periodontal diseases had 17% increased risk of cancer compared with the expected counts for the corresponding age and sex groups (SIR: 1.17; 95% CI: 1.04–1.3, P = 0.006). The increased cancer risk was statistically significant in women (SIR: 1.24; 95% CI: 1.05–1.45, P = 0.008) but not in men. Among women with periodontal disease, the risks of breast cancer (SIR: 2.19) and head and neck cancer (SIR: 4.71) were significantly increased. Among men, the risks of prostate cancer (SIR: 1.84), head and neck cancer (SIR: 3.55), and hematological cancers (SIR: 1.76) were significantly increased.

Conclusion: This study showed that periodontal diseases were associated with increased risk of several cancers. Besides other well-known benefits for health, the provision of oral/dental health should be considered and employed as a cancer prevention measure.
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http://dx.doi.org/10.3906/sag-1812-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018248PMC
June 2019

Treatment outcomes of prostate cancer patients with Gleason score 8-10 treated with definitive radiotherapy : TROD 09-001 multi-institutional study.

Strahlenther Onkol 2019 Oct 29;195(10):882-893. Epub 2019 May 29.

Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, 06100, Ankara, Turkey.

Purpose: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era.

Methods: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT.

Results: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5‑year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10.

Conclusions: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.
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http://dx.doi.org/10.1007/s00066-019-01476-zDOI Listing
October 2019

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T).

Nord J Psychiatry 2019 Feb 9;73(2):132-140. Epub 2019 Apr 9.

m Child and Adolescent Psychiatry Department, Medical Faculty , Istanbul University , Istanbul , Turkey.

Aim: The aim of this study was to determine the prevalence of childhood psychopathologies in Turkey.

Method: A nation-wide, randomly selected, representative population of 5830 children (6-13 years-old) enrolled as a 2nd,3rd or 4th grade student in 30 cities were evaluated for presence of a psychiatric or mental disorder by a Sociodemographic Form, Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL), and DSM-IV-Based Screening Scale for Disruptive Behavior Disorders in Children and Adolescents scales. Impairment criterion was assessed via a 3 point-Likert scale by the parent and the teacher independently.

Results: Overall prevalence of any psychopathology was 37.6% without impairment criterion, and 17.1% with impairment criterion. Attention-deficit hyperactivity disorder was the most frequent diagnosis, followed by anxiety (19.5% and 16.7% without impairment, 12.4% and 5.3% with impairment, respectively). Lower education level and presence of a physical or psychiatric problem of the parents were independent predictors of any psychopathology of the offspring.

Conclusion: This is the largest and most comprehensive epidemiological study to determine the prevalence of psychopathologies in children and adolescents in Turkey. Our results partly higher than, and partly comparable to previous national and international studies. It also contributes to the literature by determining the independent predictors of psychopathologies in this age group.
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http://dx.doi.org/10.1080/08039488.2019.1574892DOI Listing
February 2019

Response to the letter to the editor: Comment on "Does Kinesiotaping improve pain and functionality in patients with newly diagnosed lateral epicondylitis?"

Knee Surg Sports Traumatol Arthrosc 2021 03 21;29(3):1008-1010. Epub 2019 Mar 21.

Department of Physiotherapy and Rehabilitation, Hacettepe University Faculty of Health Sciences, 06100, Ankara, Turkey.

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http://dx.doi.org/10.1007/s00167-019-05454-xDOI Listing
March 2021

Reproductive cancer risk factors among relatives of cancer patients in a tertiary oncology center.

BMC Cancer 2019 Feb 15;19(1):154. Epub 2019 Feb 15.

Department of preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Background: The aim of this study was to evaluate the prevalence of some gynecological cancer risk factors in a population of female relatives of cancer patients in Hacettepe University Oncology Hospital. Additionally, what are the levels of the women's awareness /behavior toward available screening tools?

Methods: An individual cancer risk assessment questionnaire has been developed in the Department of Preventive Oncology, which questions the medical history, health behaviors and cancer awareness, as well as their behavior toward available cancer screening tools.

Results: The mean age of the study population was 45.7 ± 12.2 years. Median age at menarche was 13 years (IQR, 12-14), 6.9% of the women reported their menarche was before age of 12. About 11.1% of the women had intercourse before age of 18. The median age at first delivery was 22 years. Median BMI was 24.9, with 18.3% of population having obesity. Of the women 65% were current/past smokers. Sixty-two percent of the women had never used condom. About 8% of the women were unaware about mammography and 17.7% about the Pap test.

Conclusions: This study has documented high tobacco use, low protective condom use and low rates of physical activity. Percentage of some risk factors like early menarche was lower than what was suggested for general Turkish population. Awareness and behavior of the women were better about mammography when compared to the Pap test. Considering our results, some measures should be put in place to increase people's awareness, and to modify their behavior toward cancer prevention.
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http://dx.doi.org/10.1186/s12885-019-5350-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377741PMC
February 2019

Low Copeptin Levels in Patients With Intradialytic Hypotension.

Ther Apher Dial 2019 Oct 1;23(5):460-466. Epub 2019 Feb 1.

Department of Nephrology, Gazi University Faculty of Medicine, Ankara, Turkey.

Intradialytic hypotension (IDH) is related to high morbidity and mortality. There is evidence that arginine-vasopressin (AVP) responses could play a role. Copeptin is a reliable biomarker of AVP. In this study, copeptin, aldosterone, epinephrine, and norepinephrine levels in patients with IDH were evaluated throughout a hemodialysis (HD) session and compared with the control group. The study includes 15 patients who were normotensive during HD and 15 patients with IDH with a minimum HD vintage of 1 year. Blood samples were collected before the initiation of an HD session (T ), in the mid-session for control group, 30 min after mean arterial pressure drop for IDH patients (T ), and at the end of the session (T ). Groups had similar demographic features and health parameters, interdialytic weight gains, and ultrafiltration amounts. The IDH group had a mean arterial pressure decline of 39.9 (±6.4) mm Hg. Copeptin levels of the control group increased an average of 79.9 (±97.5) pmol/L at T and an additional 24.8 (±33.9) pmol/L at T . In the IDH group, copeptin level increases at T and T were 3.2 (±5.5) pmol/L and 34 (±44.6) pmol/L, respectively Copeptin levels of the IDH group were significantly lower at T (P < 0.001) and at the T -T interval than control group (P = 0.05). In the control group, aldosterone levels distinctly decreased, and in the IDH group, aldosterone levels were elevated (P < 0.001). Small changes were detected in epinephrine and norepinephrine levels for both groups but did not reach significance (P = 0.6 and P = 0.3, respectively). Lower copeptin level alterations suggest inadequate AVP responses in patients with IDH.
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http://dx.doi.org/10.1111/1744-9987.12784DOI Listing
October 2019

Learning effect of dynamic postural stability evaluation system.

J Back Musculoskelet Rehabil 2019 ;32(1):7-14

Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey.

Background: Repeated exposure to a given perturbation of the postural control system has been shown to cause learning of more efficient postural strategies for maintaining balance both within a session and over time. It is important to show whether outcomes from treatment strategies are related to the effectiveness of training or are the result of the learning of the test process.

Objective: To investigate the learning effect of the dynamic postural stability evaluation system.

Methods: We studied 20 healthy young subjects (13 females and 7 males), with a mean age of 22.3 ± 1.9 years. Limits of stability and postural sway were assessed. All participants completed the standardized dynamic postural stability evaluation test (Bertec, Bertec Corporation, Columbus, OH, USA) seven times. The test was performed in both eyes open and eyes closed conditions.

Results: There were differences in the limits of stability scores for backward (p= 0.042), left side (p= 0.05), and the total score (p= 0.04). There were significant differences in postural sway anteroposterior direction in perturbed surface with eyes closed condition (p= 0.004) and total limits of stability scores of perturbed surface with eyes closed condition (p= 0.046).

Conclusions: The study showed that balance test scores stabilized at different sessions from 1st to 3rd assessment period. Maximum normalized scores were reached at the third trial.
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http://dx.doi.org/10.3233/BMR-181172DOI Listing
March 2019

Beta-Hydroxy-Beta-Methyl-Butyrate, L-glutamine, and L-arginine Supplementation Improves Radiation-Induce Acute Intestinal Toxicity.

J Diet Suppl 2019 3;16(5):576-591. Epub 2018 Jul 3.

Selcuk University, Department of Medical Oncology , Konya , Turkey.

We aimed to evaluate effects of β-hydroxy-β-methylbutyrate, L-glutamine, and L-arginine (HMB/GLN/ARG) on radiation-induced acute intestinal toxicity. Forty rats were divided into four groups: group (G) 1 was defined as control group, and G2 was radiation therapy (RT) control group. G3 and G4 were HMB/GLN/ARG control and RT plus HMB/GLN/ARG groups, respectively. HMB/GLN/ARG started from day of RT and continued until the animals were sacrificed 10 days after RT. The extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis were quantified on histological sections of intestinal mucosa. Statistical analyses were performed using the analysis of variance (ANOVA) test. There were significant differences between study groups regarding extent of surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis and crypt distortion, regenerative atypia, vascular dilatation and congestion, and fibrosis ( values were 0.019 for fibrosis, <.001 for the others). Pair-wise comparisons revealed significant differences regarding surface epithelium smoothing, villous atrophy, lamina propria inflammation, cryptitis, vascular dilatation, and congestion between G2 and G4 ( values were <.001, .033, <.001, .007, and <.001, respectively). Fibrosis score was significantly different only between G1 and G2 ( = .015). Immunohistochemical TGF-β score of G2 was significantly higher than G1 and G3 ( values were .006 and .017, respectively). There was no difference between TGF-β staining scores of G2 and G4. Concomitant use of HMB/GLN/ARG appears to ameliorate radiation-induced acute intestinal toxicity; however, this finding should be clarified with further studies.
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http://dx.doi.org/10.1080/19390211.2018.1472709DOI Listing
February 2020

Improving Microcirculatory Reperfusion Reduces Parenchymal Oxygen Radical Formation and Provides Neuroprotection.

Stroke 2018 05 18;49(5):1267-1275. Epub 2018 Apr 18.

From the Institute of Neurological Sciences and Psychiatry (A.T.-S., M.Y., Y.G.-O., S.E.E., H.K., T.D.)

Background And Purpose: Reperfusion is the most significant determinant of good outcome after ischemic stroke. However, complete reperfusion often cannot be achieved, despite satisfactory recanalization. We hypothesized that microvascular protection was essential for achieving effective reperfusion and, hence, neuroprotection. To test this hypothesis, we have developed an in vivo model to differentially monitor parenchymal and vascular reactive oxygen species (ROS) formation. By comparing the ROS-suppressing effect of N-tert-butyl-α-phenylnitrone (PBN) with its blood-brain barrier impermeable analog 2-sulfo-phenyl-N-tert-butylnitrone (S-PBN), we assessed the impact of vascular ROS suppression alone on reperfusion and stroke outcome after recanalization.

Methods: The distal middle cerebral artery was occluded for 1 hour by compressing with a micropipette and then recanalized (n=60 Swiss mice). ROS formation was monitored for 1 hour after recanalization by intravital fluorescence microscopy in pial vasculature and cortical parenchyma with topically applied hydroethidine through a cranial window. PBN (100 mg/kg) or S-PBN (156 mg/kg) was administered shortly before recanalization, and suppression of the vascular and parenchymal hydroethidine fluorescence was examined (n=22). Microcirculatory patency, reperfusion, ischemic tissue size, and neurological outcome were also assessed in a separate group of mice 1 to 72 hours after recanalization (n=30).

Results: PBN and S-PBN completely suppressed the reperfusion-induced increase in ROS signal within vasculature. PBN readily suppressed ROS produced in parenchyma by 88%. S-PBN also suppressed the parenchymal ROS by 64% but starting 40 minutes later. Intriguingly, PBN and S-PBN comparably reduced the size of ischemic area by 65% and 48% (>0.05), respectively. S-PBN restored the microvascular patency and perfusion after recanalization, suggesting that its delayed parenchymal antioxidant effect could be secondary to improved microcirculatory reperfusion.

Conclusions: Promoting microvascular reperfusion by protecting vasculature can secondarily reduce parenchymal ROS formation and provide neuroprotection. The model presented can be used to directly assess pharmacological end points postulated in brain parenchyma and vasculature in vivo.
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http://dx.doi.org/10.1161/STROKEAHA.118.020711DOI Listing
May 2018

Nephrotoxicity of piperacillin/tazobactam combined with vancomycin: should it be a concern?

Int J Antimicrob Agents 2018 Aug 9;52(2):180-184. Epub 2018 Apr 9.

Hacettepe University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Ankara, Turkey.

The combination of piperacillin/tazobactam (TZP) and vancomycin (VAN) provides a wide spectrum of activity against many pathogens acquired in healthcare settings. However, there have been reports of increased potential for nephrotoxicity with this combination. The aim of this study was to evaluate the nephrotoxic effect of TZP+VAN and to compare it with that of TZP and VAN monotherapies as well as VAN + meropenem (MEM), another broad-spectrum combination. A total of 402 patients receiving any of the antimicrobial regimens for >48 h were evaluated retrospectively over a 2-year period (2012-2013). Patients admitted to the intensive care unit, those with a baseline serum creatinine >2.0 mg/dL, patients on haemodialysis or peritoneal dialysis, pregnant women and those in septic shock were excluded. The presence and severity of acute kidney injury (AKI) was assessed according to the AKIN criteria. The incidence of AKI was significantly higher in the TZP+VAN group (41.3%) compared with the TZP (16.0%), VAN (15.7%) and VAN+MEM (10.1%) groups (P < 0.001). In the multivariate analysis, the risk of AKI increased 3.5-fold in patients treated with TZP+VAN and 1.7-fold in those who were receiving a potentially nephrotoxic drug when the antibiotic regimen was started compared with patients treated with VAN alone. Combined use of TZP+VAN carries a much higher risk of AKI than either antibiotic monotherapy regimen. Therefore, this broad-spectrum combination should be used cautiously in patients with a high likelihood of developing kidney injury.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.03.024DOI Listing
August 2018

[Response With Methylphenidate to ADHD-Like Symptoms in Pervasive Developmental Disorder: Does CES-1 Enzyme Gene Polymorphism Have a Role?]

Turk Psikiyatri Derg 2017 ;28(2):89-94

Objective: Methylphenidate is the first-choice medication for the Pervasive Developmental Disorders (PDDs), and comorbid Attention Deficit Hyperactivity Disorder (ADHD). But this approach generally results with poor outcomes, and increased adverse effects. It is aimed to investigate the comparison of cases who diagnosed with PDDs and Mild Mental Retardation (MR) and cases with pure ADHD in terms of the clinical response to MPH. Also we aimed to investigate the relations between CES-1 polymorphism gene and the clinical response to MPH.

Methods: For clarifying this we searched for three polymorphisms (Arg199/His, Ser75/Asn, and Ile49/Val) in carboxylesterase-1 gene (CES-1) in the saliva of patients diagnosed with PDD+ADHD. Also, we assessed the clinical response to MPH by dimensional approach using the Attention Deficit Hyperactivity Disorder Rating Scale IV and Clinical Global Impression-Improvement scale.

Results: PDD+ADHD groups had significantly higher Arg199/His polymorphism, and clinically responded poorer with symptoms sometimes even worsening to the MPH treatment compared with "pure" ADHD and ADHD+MR groups.

Conclusion: This is the first study that an association between Arg199/His polymorphism in CES1 and altered treatment response to MPH in patients with PDD that presents with symptoms of ADHD.
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November 2018

Immune Thrombocytopenia Induced by Nivolumab in a Metastatic Non-Small Cell Lung Cancer Patient.

Oncol Res Treat 2017 19;40(10):621-622. Epub 2017 Sep 19.

Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

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http://dx.doi.org/10.1159/000477968DOI Listing
August 2019

Does Kinesiotaping improve pain and functionality in patients with newly diagnosed lateral epicondylitis?

Knee Surg Sports Traumatol Arthrosc 2018 Mar 24;26(3):938-945. Epub 2017 Aug 24.

Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Hacettepe University, 06100, Ankara, Turkey.

Purpose: This study aimed to compare the short-term effects of kinesiotaping and extracorporeal shock wave therapy (ESWT) along with physiotherapy on pain, functionality, and grip strength in patients with newly diagnosed lateral epicondylitis undergoing rehabilitation.

Methods: Forty-five voluntary patients (mean age 48 years) were randomly assigned to three groups. Patients in all groups received physiotherapy consisting of a cold pack and transcutaneous electrical nerve stimulation five times per week for a total of 15 sessions and a home exercise programme including stretching and eccentric strength exercises. In the second group, patients received kinesiotaping 5 days a week for 3 weeks. In the third group, ESWT was applied three times for 3 weeks. Patients were assessed by visual analogue scale for pain intensity, pain-free grip strength using a hand dynamometer, Cyriax Resisted Muscle Test, and Patient-Rated Tennis Elbow Evaluation Scale. All measurements were collected at baseline and after treatment.

Results: There were no significant differences in the demographic characteristics of the patients in all groups at baseline. Intra-group analysis revealed that pain intensity decreased, whereas maximum grip strength and functionality increased in all groups at the end of the treatment (p < 0.05). Inter-group analysis revealed that the kinesiotaping group yielded better results in decreasing pain intensity than the other groups (p < 0.05). The kinesiotaping group (p < 0.001) and ESWT group (p = 0.002) yielded better results in improving functionality than the physiotherapy group. There were significant differences in recovering pain-free grip strength in the kinesiotaping group (p < 0.05).

Conclusion: Kinesiotaping was found to be effective for decreasing pain intensity, recovering grip strength, and improving functionality in patients with lateral epicondylitis undergoing rehabilitation.

Level Of Evidence: Therapeutic study, Level II.
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http://dx.doi.org/10.1007/s00167-017-4691-7DOI Listing
March 2018

A correlation study of fluorouracil pharmacodynamics with clinical efficacy and toxicity.

Tumori 2018 Jun 8;104(3):157-164. Epub 2018 May 8.

1 Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara - Turkey.

Purpose: Plasma 5-fluorouracil (5-FU) concentrations vary greatly between individuals who have received standard dosage. Pharmacokinetic adjusted doses have been hypothesized to overcome the possibility of potential toxicity and ineffectiveness related to inappropriate plasma levels of 5-FU. In this study, we prospectively investigated the clinical benefit and toxicity of 5-FU in relation to its pharmacokinetic properties.

Methods: Pharmacokinetics, effectiveness, and toxicity of 5-FU were investigated in 101 patients. The 5-FU pharmacokinetics were measured on day 2 of chemotherapy infusions. Clinicodemographic characteristics are outlined.

Results: All 101 patients who received adjuvant chemotherapy were alive at the end of a median 45 months of the follow-up period. At least one grade 1 adverse event (AE) was observed in 69.3% of the patients and grade two AEs were observed in 10.1% of the patients. The 5-FU levels ranged between 103 and 4311 µg/L and area under the curve (AUC) measurements ranged between 4.5 and 189.7 mg min/L. Pharmacokinetic measurements were not significantly correlated with clinical efficacy (log-rank p = 0.21). However, higher AUC levels were positively correlated with toxicity (p = 0.02) and with the severity of adverse events. The risks of mucositis (odds ratio [OR] 1.45; p = 0.042) and neurotoxicity (OR 2.01; p = 0.009) were significantly increased in a logistic regression model.

Conclusions: There is no clear evidence that increased plasma levels or pharmacokinetic adjusted doses of 5-FU were related to better efficacy. However, toxicity might be closely associated with increased plasma levels of 5-FU. Toxicities can be deferred via dose adjustments without any expense in efficacy.
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http://dx.doi.org/10.5301/tj.5000652DOI Listing
June 2018

The effect of glutamine and arginine-enriched nutritional support on quality of life in head and neck cancer patients treated with IMRT.

Clin Nutr ESPEN 2016 Dec 13;16:30-35. Epub 2016 Sep 13.

Hacettepe University, Faculty of Medicine, Department of Radiation Oncology, Ankara, Turkey.

Background And Aims: Oral mucositis and esophagitis are common acute toxicities of radiotherapy (RT) for head and neck cancer (HNC). In order to decrease the rates of these toxicities, we compared quality of life in HNC patients that did and did not receive a glutamine and arginine-enriched solution (GAES) during RT.

Methods: A total of 29 patients received intensity-modulated radiotherapy (IMRT); 15 used GAES b.i.d. during the treatment, and a matched cohort of 14 patients did not. Patients were administered the EORTC QLQ-C30, QLQ-H&N35 and QLQ-OES18 questionnaires on the 1st, 15th, and last days of IMRT.

Results: The global health status, functional and symptom scale scores were similar in both groups on the 1st day of IMRT. On the 15th and last days, the scores of social functions (p = 0.01 and p = 0.012), pain (p = 0.002 and p = 0.002), appetite (p = 0.01 and p = 0.02), dry mouth (p = 0.001 and p = 0.03), sticky saliva (p = 0.003 and p = 0.04), trouble with taste (p = 0.001 and p = 0.03), trouble with social eating (p = 0.004 and p = 0.006), and swallowing problems (p = 0.002 and p = 0.046) were significantly worse in the control group.

Conclusions: Quality of life is negatively affected by IMRT; however, use of GAES may mediate this negative effect.
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http://dx.doi.org/10.1016/j.clnesp.2016.08.003DOI Listing
December 2016

Successful Treatment Response with Aripiprazole Augmentation of SSRIs in Refractory Obsessive-Compulsive Disorder in Childhood.

Child Psychiatry Hum Dev 2017 10;48(5):699-704

Institute on Drug Abuse, Toxicology and Pharmaceutical Science, Ege University, Izmir, Turkey.

The aim of this study is to evaluate the aripiprazole augmentation of selective seratonine reuptake inhibitors (SSRIs) in children and adolescents with treatment-resistant OCD. Forty-eight children and adolescents (14 girls, 34 boys), who are non-responders to treatment with at least two types of SSRIs and CBT, were administered a 12-week of augmentation. Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I) sub-scales were used for evaluation of the treatment outcomes. The results showed that total CY-BOCS scores were decreased from 33.3 ± 7.5 to 11.7 ± 9.3 (p < 0.001), CGI-S scores decreased from 6.3 ± 0.9 to 2.7 ± 1.6 (p < 0.001), and CGI-I scores improved from 4.3 ± 0.6 to 2.2 ± 1.1 (p < 0.001). Sensitivity analyses in 29 patients without SSRI dose escalation along with aripiprazole augmentation have also revealed that improvement effect was still significant, and CY-BOCS scores were improved from 34.2 ± 7.9 to 13 ± 10.3, CGI-S improved from 6.4 ± 1.0 to 3.0 ± 1.7, and CGI-I improved from 4.4 ± 1.0 to 2.3 ± 1.1 (p < 0.001 for all). Analyses revealed that a significant clinical improvement has been observed with aripiprazole augmentation. Aripiprazole augmentation of SSRIs is a promising strategy in the management of treatment-refractory OCD children and adolescents.
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http://dx.doi.org/10.1007/s10578-016-0694-8DOI Listing
October 2017

Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

Breast 2017 Apr 16;32:237-244. Epub 2016 Jun 16.

Hacettepe University Faculty of Medicine, Department of Medical Oncology, Ankara, Turkey. Electronic address:

Purpose: The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia.

Patients And Methods: Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m), overweight (OW) patients (BMI = 25-29.9 kg/m) and obese (OB) patients (BMI ≥30 kg/m). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors.

Results: In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent prognostic factors on OS (HR, 0.29; 95% CI, 0.11 to 0.79, P = 0.015, HR, 2.09; 95% CI, 1.14 to 3.83, P = 0.017, HR, 1.95; 95% CI, 1.01 to 3.77, P = 0.046, respectively).

Conclusion: It was observed that obesity was an important independent prognostic factor which has an adverse effect on pCR. Moreover it causes decreasing RFS and OS in BC patients who had received NAC. The probability of inefficient treatment in obese patients should be considered.
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http://dx.doi.org/10.1016/j.breast.2016.05.013DOI Listing
April 2017