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    An aggressive parameningeal rhabdomyosarcoma with multiple spinal cord metastases: a case report and review of the literature
    (SPRINGER, 2017) Yavas, Guler; Karabagli, Pinar; Paksoy, Yahya; Yavas, Cagdas; Karabagli, Hakan; Koksal, Yavuz
    Purpose Spinal cord metastasis from rhabdomyosarcoma (RMS) is extremely rare, with three cases reported to date. Herein, we report an aggressive case of RMS of the infratemporal fossa who which developed spinal cord metastases during treatment. Case presentation A 6-year-old girl presented with an enlarging painless mass around her right ear for 3 months. An enhanced magnetic resonance imaging (MRI) revealed a 5 x x4 x x4.5 5 cm mass on her right infratemporal fossa. A tru-cut biopsy was performed, and histopathologic examination revealed the diagnosis of rhabdomyosarcoma. At the time of the diagnosis, cerebrospinal fluid cytology was negative for malignant cells. The patient underwent induction chemotherapy. There was minimal response to chemotherapy, and the patient underwent curative radiotherapy. However, by 12th fraction of RT, the patient developed a progressive weakness on her lower extremity. Spinal MRI revealed multiple gross masses in different parts of the spinal cord. The local radiotherapy was changed toas craniospinal radiotherapy. However, two 2 weeks after the completion of the RT, the patient developed sepsis and expired because of septic shock. Conclusion Parameningeal RMS is a peculiar subgroup of RMS, which needs an aggressive approach. Despite aggressive approach, meningeal spread is the most important cause of the treatment failure. We should keept in mind that during the treatment, there can be meningeal spread towards to either the brain or spinal cord; therefore, we should follow -up the patients closely from this aspect.
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    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, Ozlem
    Adjuvant 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.
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    Comment on Sridharan V et al., 'Effects of radiation on the epidermal growth factor receptor pathway in the heart'
    (INFORMA HEALTHCARE, 2014) Yavas, Guler; Yavas, Cagdas
    [Abstract not Available]
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    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, Cetin
    To 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.
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    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, Ozlem
    The 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.
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    Does spironolactone ameliorate trastuzumab-induced cardiac toxicity?
    (CHURCHILL LIVINGSTONE, 2013) Yavas, Guler; Elsurer, Rengin; Yavas, Cagdas; Elsurer, Cagdas; Ata, Ozlem
    The 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.
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    Dosimetric comparison of 3-dimensional conformal and field-in-field radiotherapy techniques for the adjuvant treatment of early stage endometrial cancer
    (ELSEVIER SCI LTD, 2013) Yavas, Guler; Yavas, Cagdas; Acar, Hilal; Buyukyoruk, Ahmet; Cobanoglu, Gokcen; Kerimoglu, Ozlem Secilmis; Yavas, Ozlem
    Background: The purpose of this study is to compare field-in-field radiotherapy (FIF) with conformal radiotherapy (CRT) in terms of dosimetric benefits for early stage endometrial cancer patients. Materials and methods: Ten consecutive early stage endometrial cancer patients who underwent adjuvant external beam radiotherapy were included in the study. For each patient, two different treatment plans were created. FIF and CRT plans were compared for doses in the planning target volume (PTV), the organ at risk (OAR) volumes including rectum, bladder, bowel, bilateral femurs and bone marrow, the dose homogeneity index, and the monitor unit counts required for the treatment. Results: The FIF technique significantly reduced the maximum dose of the PTV, rectum, bladder, bowel, left femur, right femur and bone marrow (p values were: <0.001, 0.031, 0.003, <0.001, 0.001, 0.001 and <0.001 respectively). When the OAR volumes irradiated with >30 and >45 Gy were compared, the results were in favor of the FIF technique. The volumes of rectum, bladder, bowel, left femur, right femur and bone marrow receiving more than the prescription dose of 45 Gy were significantly reduced with FIF technique (p values were 0.016, 0.039, 0.01, 0.04, 0.037 and 0.01 respectively). The dose homogeneity index (DHI) was significantly improved with FIF technique (p < 0.001). Conclusions: FIF allowed more homogeneous dose distribution in the PTV and reduced the doses received by OAR. Considering the lower maximum doses in the OAR and PTV, FIF technique seems to be more advantageous than CRT during adjuvant radiotherapy for early stage endometrial cancer patients. (C) 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
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    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, Hidir
    The 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.
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    Giant papillary carcinoma arising in the ectopic buccal thyroid tissue
    (WILEY, 2013) Elsurer, Cagdas; Ozturk, Kayhan; Baba, Fusun; Yavas, Cagdas; Bulut, Serap
    BackgroundEctopic thyroid tissue very rarely occurs in the buccal region. Even more rarely encountered is the papillary carcinoma arising in the ectopic tissue. Methods and ResultsWe herein present a 78-year-old female patient admitted with a giant, buccal mass that developed within the previous 2 years. Physical examination revealed a vegetative mass on the left buccal region without any cervical lymphadenopathy. Magnetic resonance imaging scan showed an 8- x 6-cm solid mass with cystic components in the left buccal region and thoracic computed tomography scanning revealed pulmonary metastasis. A successful surgery including lower lip splitting was performed, and the mass was totally excised with its surrounding capsule. Histopathologic examination revealed follicular variant of papillary carcinoma of the ectopic thyroid tissue. ConclusionsTo our knowledge, our case is the first case of papillary carcinoma arising from ectopic thyroid tissue in the buccal region in the literature. (c) 2012 Wiley Periodicals, Inc. Head Neck 35: E308-E309, 2013
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    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, Ozlem
    Primary 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.
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    The Impact of Body Mass Index on Radiotherapy Technique in Patients With Early-Stage Endometrial Cancer A Single-Center Dosimetric Study
    (LIPPINCOTT WILLIAMS & WILKINS, 2014) Yavas, Guler; Yavas, Cagdas; Kerimoglu, Ozlem Secilmis; Celik, Cetin
    Objective: We aimed to evaluate the impact of body mass index on radiotherapy (RT) technique in patients with early-stage endometrial cancer. Materials and Methods: Twenty-seven consecutive patients were included in the study and divided into 3 groups with respect to their body mass index (normal weight, 18.5Y24.9 kg/m(2); overweight, 25-29.9 kg/m(2); obese, 30-39.9 kg/m(2)). Treatment plans using field-in-field (FIF) and 3-dimesional conformal RT (3D-CRT) were compared for the doses in the planning target volume (PTV), organs-at-risk (OAR) volumes, dose homogeneity index, and monitor unit counts required for the treatment. Results: The FIF technique was superior to 3D-CRT with respect to the maximum and mean doses received by OAR and dose homogeneity index values. The subgroup analyses revealed that the maximum dose received by the right femur and the mean doses received by the rectum and bladder were significantly reduced only in obese patients (Ps = 0.021, 0.008, and 0.008, respectively). The FIF technique significantly reduced the PTV volumes irradiated with greater than 105% of the prescribed dose (P < 0.001). The volumes of bowel and bone marrow receiving more than the prescribed dose of 30 Gy were significantly reduced only in obese patients (Ps = 0.025 and 0.043, respectively). The volumes of bladder, bowel, and bone marrow receiving more than the prescribed dose of 45 Gy were significantly reduced in only obese patients (Ps = 0.011, 0.011, and 0.008, respectively). Conclusions: Considering the lower maximum doses in OAR and PTV, we demonstrate the FIF technique to be more advantageous than 3D-CRT during adjuvant RT for early-stage endometrial cancer patients. This advantage is more prominent in obese patients. Therefore, FIF technique represents an effective pelvic RT treatment option for obese patients in clinics that do not have access to or prefer an alternative to intensity-modulated RT.
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    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, Cagdas
    Kaposi 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.
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    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, Sema
    We 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.
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    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, Ozlem
    Purpose: 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.
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    Prospective Assessment of Quality of Life and Psychological Distress in Patients With Gynecologic Malignancy A 1-Year Prospective Study
    (LIPPINCOTT WILLIAMS & WILKINS, 2012) Yavas, Guler; Dogan, Nasuh Utku; Yavas, Cagdas; Benzer, Nilgun; Yuce, Deniz; Celik, Cetin
    Objective: Our aim was to evaluate the health-related quality of life (HRQoL) and psychological distress in patients treated with radiotherapy (RT) for gynecologic malignancy. Methods: Fifty-seven women with either cervical or endometrial cancer were prospectively enrolled. We assessed HRQoL at baseline (after surgery before RT), at the end of RT, and during follow-up (every 3 months thereafter) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30), European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 24 (EORTC QLQ-CX24), and Hospital Anxiety and Depression Scale. Results: We demonstrated changes in appetite loss (P = 0.03), nausea and vomiting (P = 0.02), and role function score (P = 0.003) domains of EORTC QLQ-C30. Only the mean body image score of EORTC QLQ-CX24 was significantly different during follow-up (P = 0.02). Type of surgery, histopathological diagnosis, and the menopausal and marital status of the patients affected baseline body image scores (P = 0.032, 0.004, and 0.019 and 0.005, respectively). Patients who underwent chemotherapy had higher baseline body image scores when compared with patients without any chemotherapy before RT (P = 0.028). All the complaints of patients except body image scores improved during the follow-up period. The baseline and follow-up anxiety and depression scores did not differ significantly. Conclusions: Although pelvic RT deteriorated HRQoL in gynecologic cancer, patients' improvement in HRQoL during follow-up was observed. Patients receiving RT could be reassured about the improvement of acute adverse effects in the course of treatment.