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Öğe Basal renal function reserve and mean kidney dose predict future radiation-induced kidney injury in stomach cancer patients(SPRINGER, 2014) Yavas, Guler; Elsurer, Rengin; Yavas, Cagdas; Ata, OzlemAdjuvant chemoradiotherapy (CRT) improves the survival in patients with locally advanced stomach cancer. The kidneys are the major dose-limiting organs for radiotherapy (RT) in upper abdominal cancers. We aimed to evaluate the impact of adjuvant CRT on renal function of patients with stomach cancer. Fifty-nine stomach cancer patients who underwent postoperative CRT were included. Demographic parameters (age, gender), and basal and 12th-month biochemical parameters were recorded. Mean kidney dose (MKD) administered was determined. Estimated glomerular filtration rate (eGFR) was calculated by modification of diet in renal disease formula. Fifty-nine patients were recruited (age 60.8 +/- 11.9 years; female/male 25/34; follow-up duration 15.6 +/- 9.8 months). Twenty-one patients (35.6 %) had basal eGFR < 90 ml/min/1.73 m(2). When the basal and 12th-month eGFR was compared, eGFR decreased in 27 patients (45.8 %), whereas eGFR remained stable in 32 (54.2 %) patients. Cox regression analyses revealed that a MKD a parts per thousand yen1,500 cGy and basal eGFR < 90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month (HR = 2.288, 95 % CI 1.009-5.188, p = 0.048 and HR = 2.854, 95 % CI 1.121-7.262, p = 0.028, respectively). MKD a parts per thousand yen1,500 cGy and a basal eGFR < 90 ml/min/1.73 m(2) significantly increased the risk of a decreased eGFR at 12th month. We suggest that patients with stomach cancer be evaluated for their basal renal reserve prior to RT, and it may be more convenient to further minimize the dose to the kidneys with more sophisticated RT techniques in patients with stomach cancer, more specifically in patients with decreased renal reserve.Öğe Comparison of "sandwich chemo-radiotherapy" and six cycles of chemotherapy followed by adjuvant radiotherapy in patients with stage IIIC endometrial cancer: a single center experience(SPRINGER HEIDELBERG, 2013) Dogan, Nasuh Utku; Yavas, Guler; Yavas, Cagdas; Ata, Ozlem; Yilmaz, Setenay Arzu; Celik, CetinTo compare "sandwich chemo-radiotherapy" with six cycles of chemotherapy followed by adjuvant radiotherapy with respect to tolerability and acute toxicity. Twenty-five women with surgically staged IIIC endometrial cancer were included. Treatment consisted of either three cycles of paclitaxel (175 mg/mA(2)) and carboplatin (AUC 6) on a q21-day schedule followed by irradiation (45-50.4 Gy) or six cycles of the same chemotherapy followed by radiotherapy. Acute toxicity related to either chemotherapy or radiotherapy was evaluated. Median age was 61.5 years (range 36-83 years). Eleven patients had sandwich chemo-radiotherapy, and the other 14 patients had 6 cycles of chemotherapy followed by radiotherapy. Three out of the five patients who could not complete all the cycles in the sandwich chemo-radiotherapy group had pelvic and para-aortic radiotherapy. Acute radiotherapy related grade 1-2 gastrointestinal system (GIS) and genitourinary system (GUS) toxicities were observed in 72.8 and 63.6 % of patients, respectively, for sandwich group. Undesired treatment breaks in the course of radiotherapy were observed in six patients for sandwich chemo-radiotherapy and in one patient receiving six cycles of chemotherapy followed by radiotherapy. All the patients who had undesired treatment breaks in the sandwich chemo-radiotherapy group had pelvic and para-aortic radiotherapy. Sandwich chemo-radiotherapy seems to be more toxic particularly for patients who had pelvic and para-aortic irradiation. Therefore, it might be more convenient to delay radiotherapy after six cycles of chemotherapy for patients with the indication of pelvic para-aortic radiotherapy.Öğe Comparison of the effects of aromatase inhibitors and tamoxifen on radiation-induced lung toxicity: results of an experimental study(SPRINGER, 2013) Yavas, Guler; Yavas, Cagdas; Acar, Hilal; Toy, Hatice; Yuce, Deniz; Ata, OzlemThe purpose of this study is to compare the effects of anastrozole, letrozole and tamoxifen on radiation-induced pulmonary fibrosis. Eighty female Wistar albino rats were divided into eight groups. Group (G) 1 was defined as control group. G2 was radiation therapy (RT) only group. Groups 3, 4 and 5 were tamoxifen, anastrozole and letrozole control groups respectively. Groups 6, 7 and 8 were RT plus tamoxifen, anastrozole and letrozole groups, respectively. A single dose of 12 Gy RT was given to both lungs. Tamoxifen, anastrozole and letrozole were started 1 week before the RT and continued until the animals were sacrificed 16 weeks after the RT. As an end point, the extent of pulmonary fibrosis for each rat was quantified with image analysis of histological sections of the lung. Kruskal-Wallis and Mann-Whitney U tests were used for statistical analyses. The congestion, inflammation and pulmonary fibrosis scores were significantly different between all the study groups (p values were < 0.001 for each). When compared with RT only group, concomitant RT and tamoxifen group increased the radiation-induced pulmonary fibrosis (p = 0.005). However, using either anastrozole or letrozole with RT did not increase the radiation-induced pulmonary fibrosis (p values were 0.768 and 0.752, respectively). Concomitant use of tamoxifen with RT seems to increase radiation-induced pulmonary toxicity. However, the use of both anastrozole and letrozole appears to be safe with concomitant RT, without increasing the risk of pulmonary fibrosis. This finding should be clarified with further clinical studies.Öğe Differential diagnosis between secondary and tertiary hyperparathyroidism in a case of a giant-cell and brown tumor containing mass. Findings by Tc-99m-MDP, F-18-FDG PET/CT and (99)mTc-MIBI scans(HELLENIC SOC NUCLEAR MEDICINE, 2014) Gedik, Gonca Kara; Ata, Ozlem; Karabagli, Pinar; Sari, OktayBrown tumor is one of the skeletal manifegtations of hyperparathyroidism. It is a benign but locally aggressive bone lesion and its differential diagnosis with giant cell containing skeletal tumors or metastases may be complicated. We present a male patient with chronic renal failure who was initially misdiagnosed as having a giant-cell rich neoplasm of bone in his right thumb. Diffusely increased fluorine-18 fluorodeoxyglucose (F-18-FDG) uptake in the axial and appendicular skeleton and multiple F-18-FDG avid lytic lesions suggesting multiple metastases were observed on the F-18-FDG positron emission tomography/computed tomography (PET/CT) scan. On the usual technetium-99m methylene diphosphonate (Tc-99m-MDP) bone scan we noticed diffusely increased uptake in the skeleton and two focuses with very much increased uptake, which suggested a metabolic bone disease rather than a multiple metastatic giant cell tumor or bone metastases. Additional investigation documentated increased levels of parathyroid hormone. Parathyroid hyperplasia was finally diagnosed with Tc-99m-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy. Fluorine-18-FDG avid lytic lesions were attributed to hyerparathyroidism associated brown tumors instead of multiple metastases. In conclusion, we present a patient with chronic renal insufficiency, who suffered from secondary and later from tertiary HPT with polyostotic brown tumors, which were best shown by the F-18-FDG PET/CT than by the Tc-99m-MDP or the Tc-99m-MIBI scans.Öğe Does spironolactone ameliorate trastuzumab-induced cardiac toxicity?(CHURCHILL LIVINGSTONE, 2013) Yavas, Guler; Elsurer, Rengin; Yavas, Cagdas; Elsurer, Cagdas; Ata, OzlemThe ErbB2 receptor is a proto-oncogene associated with a poor prognosis in breast cancer. Trastuzumab, a humanized anti-ErbB2 antibody currently in clinical use, has proven to be an essential tool in the immunotherapy of breast carcinoma. Additionally, ErbB2 is involved in the growth and survival pathway of adult cardiomyocytes which accounts for the trastuzumab-induced cardiotoxicity. Moreover, in metastatic breast cancer patients treated with trastuzumab, endomyocardial biopsy documented focal vacuolar changes, pleomorphic mitochondria, myocardial cell hypertrophy, and mild interstitial fibrosis on electron microscopy without accompanying light microscopic abnormalities, a finding consistent with a reversible pattern of cardiac injury. On the other hand, aldosterone and mineralocorticoid receptor (MR) researches have experienced a revival after the discovery that aldosterone and MR are not only involved in the electrolyte and volume balance but also in the pathophysiological processes of the reno-cardiovascular system. Aldosterone has both genomic and nongenotropic effects on epidermal growth factor receptor (EGFR) expression. Genomic effect induces genomic up-regulation of the EGFR protein expression via EGFR promoter, whereas nongenotropic effect leads to the EGFR transactivation resulting in persistent pathophysiological effects including formation of extracellular matrix and myocardial hypertrophy. Spironolactone, an aldosterone receptor antagonist, is known to ameliorate the cardiac damage. The underlying mechanism for the genomic interactions seem to be the stimulation of the EGFR promoter by aldosterone-bound MR, which then dose-dependently enhances the EGFR protein levels, which may be successively inhibited by spironolactone. By the light of these findings, we hypothesize that spironolactone may ameliorate trastuzumab-induced cardiotoxicity via inhibition of transactivation of the EGFR by aldosterone and reversing myocardial hypertrophy. This issue warrants further studies. (C) 2013 Elsevier Ltd. All rights reserved.Öğe The effect of Halofuginone in the amelioration of radiation induced-lung fibrosis(CHURCHILL LIVINGSTONE, 2013) Yavas, Guler; Calik, Mustafa; Calik, Goknil; Yavas, Cagdas; Ata, Ozlem; Esme, HidirThe lung is one of the most sensitive organs to ionizing radiation, and damage to normal lung tissue remains a major dose limiting factor for patients receiving radiation to the thorax. Radiation induced lung injury (RILI) which is also named as "radiation pneumonpathy" is a continuous process and regarded as the result of an abnormal healing response. It has been shown that transforming growth factor beta-1 (TGF-beta 1) plays an integral role in the radiation induced lung fibrosis formation by promoting the chemoattraction of fibroblasts and their conversion to myofibroblasts. Halofuginone is a, low molecular weight plant derived alkaloid, isolated from the Dichroa febnfuga plant that exhibits antifibrotic activity and inhibition of type I collagen synthesis. Halofuginone has been shown to protect against radiation induced soft tissue fibrosis by virtue of inhibiting various members of TFG-beta signaling pathway. By the light of these findings, we hypothesize that Halofuginone may be able to ameliorate the radiation induced lung fibrosis. (C) 2013 Elsevier Ltd. All rights reserved.Öğe HER-2 Mutations in Non-Small Cell Lung Cancer(YERKURE TANITIM & YAYINCILIK HIZMETLERI A S, 2018) Sen, Erdem; Yavas, Guler; Ata, OzlemLung cancer is a heterogeneous and complex disease. Oncogenic driver mutations are critical for lung cancer development and serve as therapeutic targets. Oncogenic driver mutations are well defined in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and reactive oxygen species-1 (ROS-1) mutations. Human epidermal growth factor receptor-2 (HER-2) positivity and anti-HER-2 treatments are well studied in breast cancer. In non-small cell lung cancer (NSCLC), these treatment approaches are under investigation. In NSCLC, mutations of HER-2 are found in 2%-4% of cases. The most commonly encountered mutations are frame insertions in exon 20. There is no evident association between HER-2 amplification and HER-2 mutations. HER-2-targeted therapy needs further clinical investigations in NSCLC.Öğe HER-2 positive primary solid neuroendocrine carcinoma of the breast: a case report and review of the literature(SPRINGER JAPAN KK, 2015) Yavas, Guler; Karabagli, Pinar; Araz, Murat; Yavas, Cagdas; Ata, OzlemPrimary pure neuroendocrine carcinoma of the breast is an extremely rare tumor. We report a case of primary solid neuroendocrine carcinoma in a 77-year-old postmenopausal woman who was admitted to the hospital with masses on her right breast and axillary region. Radical mastectomy with axillary lymph node resection was performed. Immunohistochemical stainings of the tumor cells with synaptophysin, GCDFP-15, estrogen, progesterone, and c-erbB-2 were positive. Five of 16 lymph nodes were metastatic. She did not receive adjuvant chemotherapy. After 15 months of follow-up she is free of the disease. Literature review revealed that this is the second case of HER-2 positive primary neuroendocrine tumor of the breast.Öğe Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient(HINDAWI LTD, 2016) Celik, Zeliha Esin; Celik, Murat; Sen, Erdem; Cebeci, Hakan; Ata, Ozlem; Yavas, CagdasKaposi sarcoma (KS), a vascular tumor caused by infection with human herpesvirus 8 (HHV8), is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence andmetastatic potential. We report here a 47-year-oldHIV negativemale presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenalKS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS withoutmucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.Öğe Ionizing Radiation Induces Cytokines, MMP-1, TIMP-1 and Supresses Type I Collagen mRNA Expressions in Human Gingival Fibroblasts(AKAD DOKTORLAR YAYINEVI, 2014) Yavas, Guler; Yavas, Cagdas; Bozkurt, S. Buket; Ata, Ozlem; Hakki, SemaWe aimed to evaluate the effects of ionizing radiation on the proliferation of gingival fibroblasts and the expressions of proinflammatory cytokines and matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and type I collagen (type I Col) mRNA transcripts. Gingival fibroblasts were treated with radiation doses as follows; 0.5 Gy, 1 Gy, 2 Gy, 4 Gy, 6 Gy, and 8 Gy. Expression of interleukin (IL)-1 beta, IL-6, IL-8 and, MMP-1, TIMP-1 and of type I Col mRNA transcripts in human gingival fibroblasts was determined by quantitative polymerase chain reaction (PCR) analysis. Morphology of gingival fibroblasts was evaluated using inverted microscope. Ionizing radiation decreased cell proliferation (p< 0.05) compared to the control group. Expressions of IL-1 beta, IL-6 and IL-8 were stimulated at the highest dosage of radiation (p< 0.001). In parallel to proinflammtory cytokines, MMP-1 and TIMP-1 mRNA expressions were elevated in response to higher dosage of radiation (p< 0.001). Radiation suppressed type I Col mRNA expression in response to all doses at 24 hrs (p< 0.001). In addition to basal epithelial cells of the oral mucosa, gingival fibroblasts have an important role in the pathogenesis of oral mucositis. Results of this study may help to clarify the role of gingival fibroblasts in radiation induced oral mucositis.Öğe Neutropenic Fever, Skin and Eye Toxicities Develops During Docetaxel Treatment in Metastatic Prostate Cancer: A Case Report(GALENOS YAYINCILIK, 2017) Sen, Erdem; Oner, Irem; Ata, OzlemProstate cancer is one of the most common tumors in men. Docetaxel and prednisone treatment are accepted as standard therapy in castration-resistant prostate cancer patients. Docetaxel is a chemotherapeutic drug of the taxane group that inhibits depolymerization of tubulin and has an antitumoral activity through stabilization of microtubules. It has also been reported that docetaxel therapy lead to cutaneous and eye side effects besides systemic side effects. Skin and eye toxicities are more common with weekly docetaxel treatment than three-week regimens. We would like to present our case of neutropenia, eye and skin toxicities with docetaxel chemotherapy treatment which is commonly used in metastatic prostate cancer patients.Öğe Pelvic radiotherapy does not deteriorate the quality of life of women with gynecologic cancers in long-term follow-up: A 2 years prospective single-center study(MEDKNOW PUBLICATIONS & MEDIA PVT LTD, 2017) Yavas, Guler; Yavas, Cagdas; Dogan, Nasuh Utku; Ilhan, Tolgay Tuyan; Dogan, Selen; Karabagli, Pinar; Ata, OzlemPurpose: To evaluate the emotional, sexual and health-related quality of life (HRQoL) concerns of the women with gynecologic malignancy treated with curative radiotherapy (RT). Patients and Methods: A 100 women with diagnosis of gynecologic malignancy were prospectively enrolled. HRQoL at baseline, at the end of RT and during follow-up was assessed using European Organization for Research and Treatment of Cancer QoL Questionnaire-C30 (EORTC QLQ-C30), EORTC QLQ-cervical cancer module 24, and Hospital Anxiety and Depression Scale. Results: The appetite loss, diarrhea, fatigue, dyspnea, insomnia, nausea and vomiting, pain scores, and sexual activity and sexual enjoyment scores were deteriorated after RT (P = 0.02 for pain scores and P < 0.001 for all other). Body image scores were higher in patients with endometrial cancer (P < 0.01). The emotional function, nausea and vomiting, body image and symptom experience scores were higher in patients who underwent chemotherapy (P = 0.04 and P = 0.01). All the complaints of patients improved during follow-up period. The global health status scores and the level of depression deteriorated in patients with locoregional recurrent disease and distant metastasis. The anxiety (P = 0.001) and depression (P = 0.007) levels were higher in basal and after-RT visits but then decreased through the subsequent follow-up visits. Conclusion: Although pelvic RT deteriorated HRQoL in patients with gynecologic malignancy, HRQoL improved during the follow-up period. The progressive disease had a negative impact on HRQoL.
