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Item GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro(OXFORD UNIV PRESS, 2015-01-01) Bildik, Gamze; Akin, Nazli; Senbabaoglu, Filiz; Sahin, Gizem Nur; Karahuseyinoglu, Sercin; Ince, Umit; Taskiran, Cagatay; Selek, Ugur; Yakin, Kayhan; Guzel, Yilmaz; Ayhan, Cem; Alper, Ebru; Cetiner, Mustafa; Balaban, Basak; Mandel, Nil Molinas; Esen, Tarik; Iwase, Akira; Urman, Bulent; Oktem, OzgurSTUDY QUESTION: Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? SUMMARY ANSWER: The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. WHAT IS KNOWN ALREADY: Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. STUDY DESIGN, SETTINGS, SIZE AND DURATION: This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. MAIN RESULTS AND THE ROLE OF CHANCE: The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples. GnRHa co-administered with chemotherapy agents stimulated its receptors and raised intracellular cAMP levels. But it neither activated anti-apoptotic pathways nor prevented follicle loss, DNA damage and apoptosis induced by these drugs. LIMITATIONS, REASONS FOR CAUTION: Our findings do not conclusively rule out the possibility that GnRHa may offer protection, if any, through some other mechanisms in vivo. WIDER IMPLICATIONS OF THE FINDINGS: GnRH agonist treatment with chemotherapy does not prevent or ameliorate ovarian damage and follicle loss in vitro. These data can be useful when consulting a young patient who may wish to receive GnRH treatment with chemotherapy to protect her ovaries from chemotherapy-induced damage.Item Conspicuity of Peripheral Zone Prostate Cancer on Computed Diffusion-Weighted Imaging: Comparison of cDWI(1500), cDWI(2000), and cDWI(3000)(HINDAWI LTD, 2014-01-01) Vural, Metin; Ertas, Gokhan; Onay, Aslihan; Acar, Omer; Esen, Tarik; Saglican, Yesim; Zengingonul, Hale Pinar; Akpek, SerginIntroduction and Objective. Disadvantages associated with direct high b-value measurements may be avoided with use of computed diffusion-weighted imaging (cDWI). The purpose of this study is to assess the diagnostic performance of cDWI image sets calculated for high b-values of 1500, 2000, and 3000 s/mm(2). Materials and Methods. Twenty-eight patients who underwent multiparametric MRI of the prostate and radical prostatectomy consecutively were enrolled in this retrospective study. Using a software developed at our institute, cDWI 1500, cDWI 2000, and cDWI 3000 image sets were generated by fitting a monoexponential model. Index lesions on cDWI image sets were scored by two radiologists in consensus considering lesion conspicuity, suppression of background prostate tissue, distortion, image set preferability, and contrast ratio measurements were performed. Results. Lesion detection rates are the same for computed b-values of 2000 and 3000 s/ mm 2 and are better than b-values of 1500 s/ mm(2). Best lesion conspicuity and best background prostate tissue suppression are provided by cDWI(3000) image set. cDWI(2000) image set provides the best zonal anatomical delineation and less distortion and was chosen as the most preferred image set. Average contrast ratio measured on these image sets shows almost a linear relation with the b-values. Conclusion. cDWI 2000 image set with similar conspicuity and the same lesion detection rate, but better zonal anatomical delineation, and less distortion, was chosen as the preferable image set.Item Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report(ELSEVIER SCI LTD, 2016-01-01) Acar, Omer; Mut, Tuna; Saglican, Yesim; Sag, Alan Alper; Falay, Okan; Selcukbiricik, Fatih; Tabak, Levent; Esen, TarikINTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the {[}18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20\% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic. (C) 2016 The Authors. Published by Elsevier Ltd. on behalf of IJS Publishing Group Ltd.Item Bilateral renal cell carcinoma with leiomyomatous stroma: A rare entity diagnosed synchronously and treated surgically in a staged fashion(AVES, 2017-01-01) Kiremit, Murat Can; Acar, Omer; Saglican, Yesim; Esen, TarikRenal cell carcinoma (RCC) accounts for approximately 3\% of adult malignancies and 90-95\% of kidney neoplasms. Renal cell carcinoma with leiomyomatous stroma (RCCLS) is an extremely rare histopathological entity based on available literature data. Herein, we report a 31-year-old male with incidentally detected synchronous bilateral renal masses who was eventually found to harbor RCCLS after being operated sequentially via nephron-sparing surgery.