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Öğe Breast Cancer Subtypes and Prognosis: Answers to Subgroup Classification Questions, Identifying the Worst Subgroup in Our Single-Center Series(Dove Medical Press Ltd, 2022) Cosar, Rusen; Sut, Necdet; Ozen, Alaattin; Tastekin, Ebru; Topaloglu, Sernaz; Cicin, Irfan; Nurlu, DilekPurpose: Many studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center.Methods: The records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan-Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis.Results: Statistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 +/- 7.17 months of DFS and 125.45 +/- 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 +/- 6.4 months and OS was 118.14 +/- 6.16. Patients who did not receive Herceptin had 92.79 +/- 18 months of DFS and 94.44 +/- 15.23 months of OS.Conclusion: The HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.Öğe Capecitabine-related intracranial hypotension syndrome mimicking dural metastasis in a breast cancer patient: Case report and review of the literature(Medknow Publications, 2010) Cosar-Alas, Rusen; Alas, Aykan; Ozen, Alaattin; Denizli, Bengu; Saynak, Mert; Uzunoglu, Sernaz; Aydogdu, NurettinSpontaneous intracranial hypotension (SICH) is an entity, which is secondary to iatrogenic manipulation and breaching of dura. Postural headache in patients should be suspected, cranial magnetic resonance imaging (MRI) is essential for precise diagnosis. Hallmark of MRI is regular shape of pachymeningeal gadolinium enhancement and subdural effusion. It may mimic central nervous system (CNS) metastasis. Prevention of such cases from receiving cranial radiotherapy by misinterpretation of the gadolinium enhancement as CNS metastasis is an important issue. Capecitabine is an antineoplastic agent, of which metabolites can cross blood-brain barrier in CNS via epithelial tissue. It may cause decrease in CSF production. SICH might be the clinical reflection of this decrease in CSF production. Review of the English literature revealed limited data because of the very little experience with oncologic patients suffering from intracranial hypotension. We report a case of spontaneous intracranial hypotension during capecitabine treatment. Patient was completely well following drug discontinuation and supportive treatment.Öğe Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods(Medknow Publications & Media Pvt Ltd, 2015) Yurut-Caloglu, Vuslat; Caloglu, Murat; Eskiocak, Sevgi; Tastekin, Ebru; Ozen, Alaattin; Kurkcu, Nukhet; Oz-Puyan, FulyaPurpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC) and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7); irradiation alone RT: radiation therapy (RT, n = 8); amifostine plus irradiation (AMI + RT, n = 8); LC plus irradiation (LC + RT, n = 8); LC and sham irradiation (LC, n = 7); and amifostine and sham irradiation (AMI, n = 7). The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg) and amifostine (200 mg/kg) was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA) and advanced oxidation protein product (AOPP) were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P:0.005 and P < 0.0001). LC increased the median number of antral follicles and corpus luteum (P:0.009 and P < 0.0001, respectively). Amifostine improved median corpus luteum numbers but not antral follicle (P < 0.000, P > 0.05). The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P < 0.0001, respectively). MDA and AOPP levels were significantly reduced by LC (P:0.003, P < 0.0001) and amifostine (P < 0.0001, P:0.018). When comparing CONT group with AMI + RT and LC + RT groups, MDA and AOPP levels were similar (P > 0.005). The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005). Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.Öğe CYCLIN D1 A870G POLYMORPHISM AND PROGNOSIS OF NON-SMALL CELL LUNG CANCER(Lippincott Williams & Wilkins, 2011) Kocak, Zafer; Ozen, Alaattin; Cakina, Suat; Saynak, Mert; Gulyasar, Tevfik; Sipahi, Tammam[Abstract Not Available]Öğe Does Gender Difference Effect Radiation-Induced Lung Toxicity? An Experimental Study by Genetic and Histopathological Predictors(Radiation Research Soc, 2022) Cosar, Rusen; Ozen, Alaattin; Tastekin, Ebru; Sut, Necdet; Cakina, Suat; Demir, Selma; Parlar, SuleSeveral studies have reported differences in radiation toxicity between the sexes, but these differences have not been tested with respect to histopathology and genes. This animal study aimed to show an association between histopathological findings of radiation-induced lung toxicity and the genes ATM, SOD2, TGF-beta 1, XRCC1, XRCC3 and HHR2. In all, 120 animals were randomly divided into 2 control groups (male and female) and experimental groups comprising fifteen rats stratified by sex, radiotherapy (0 Gy vs. 10 Gy), and time to sacrifice (6, 12, and 24 weeks postirradiation). Histopathological evaluations for lung injury, namely, intra-alveolar edema, alveolar neutrophils, intra-alveolar erythrocytes, activated macrophages, intra-alveolar fibrosis, hyaline arteriosclerosis, and collapse were performed under a light microscope using a grid system; the evaluations were semi quantitatively scored. Then, the alveolar wall thickness was measured. Real-time quantitative reverse transcription PCR (RT-qPCR) was used to determine gene expression differences in ATM, TGF-beta 1, XRCC1, XRCC3, SOD2 and HHR2L among the groups. Histopathological data showed that radiation-induced acute, subacute, and chronic lung toxicity were worse in male rats. The expression levels of the evaluated genes were significantly higher in females than males in the control group, but this difference was lost over time after radiotherapy. Less toxicity in females may be attributable to the fact that the expression of the evaluated genes was higher in normal lung tissue in females than in males and the changes in gene expression patterns in the postradiotherapy period played a protective role in females. Additional data related to pulmonary function, lung weights, imaging, or outcomes are needed to support this data that is based on histopathology alone. (C) 2022 by Radiation Research SocietyÖğe Dural sinus vein thrombosis in a patient with colon cancer treated with FOLFIRI/bevacizumab(Wolters Kluwer Medknow Publications, 2009) Ozen, Alaattin; Cicin, Irfan; Sezer, Atakan; Uzunoglu, Sernaz; Saynak, Mert; Genchellac, Hakan; Karagol, HakanThe adverse effects of regimes in cancer treatment have forced us to change to new targeted therapy options. Understanding these side effects, which can lead to discontinuation of the new therapy strategies, will allow the clinical management of these side effects and result in continuing therapies with effective medications. Bevacizumab, which is an IgG1 antibody against vascular endothelial growth factor, has side effects such as proteinuria, hypertension, venous and arterial thromboembolic events, and hemorrhage. This is the first reported case of dural sinus vein thrombosis, during the treatment with bevacizumab.Öğe Eccrine porocarcinoma: a case report and literature review(Kare Publ, 2007) Saynak, Mert; Kocak, Zafer; Altaner, Semsi; Ozen, Alaattin; Cosar Alas, Rusen; Yurut Caloglu, Vuslat; Uregen, BurcuEccrine porocarcinoma is a rare malignant sweat gland tumor. The lower extremity represents the most common tumor site for this entity. Surgical excision seems to be the best treatment choice. The surgical margins should be free of tumor, otherwise a local recurrence is most likely. Regional lymph node dissection should be performed if there is evidence of lymphadenopathy. Here, we present clinical and pathological findings of a 69 years old woman diagnosed with eccrine porocarcinoma arising from the skin of the trunk.Öğe THE EFFECT OF GENDER ON RADIATION-INDUCED ACUTE LUNG INJURY IN A RAT MODEL(Lippincott Williams & Wilkins, 2012) Kocak, Zafer; Bilal, Burcu U.; Cosar, Rusen; Altaner, Semsi; Ozen, Alaattin; Cukurcayir, Funda[Abstract Not Available]Öğe Hypertrophic osteoarthropathy associated with lung cancer: a case report(Kare Publ, 2007) Ozen, Alaattin; Saynak, Mert; Kocak, Zafer; Bayir-Angin, Gulden; Uregen, Burcu; Cosar-Alas, Rusen; Cicin, IrfanMalignant neoplasms are sometimes associated with a variety of paraneoplastic rheumatic syndromes. Hypertrophic osteoarthropathy is one of these syndromes and the vast majority of cases are associated with intra thoracic neoplasms mainly broncogenic cancer. Hypertrophic osteoarthropathy (HOA) is characterized by clubbed fingers and periosteal new bone formation. Etiologically, it can be divided into primary and secondary HOA. The major clinical manifestation was severe bilateral leg pain. The pathogenesis of the disease remains unclear. Bone scintigraphy is a sensitive method to detect HOA. In this case, a 49-year-old man who had hypertrophic pulmonary osteoarthropathy associated with advanced stage non-small cell lung carcinoma is presented and a review of the literature is performed.Öğe Primary unknown solitary brain metastasis: brain recurrence alone(Kare Publ, 2007) Bayir Angin, Goden; Saynak, Mert; Kocak, Zafer; Ozen, Alaattin; Alas, Rusen Cosar; Caloglu, Vuslat Yurut; Caloglu, MuratA 53-year-old male patient presented with complaints of headache and paresis in left arm. Cranial computerized tomography and magnetic resonance imaging (MRI) demonstrated a mass in the right parietal region. The solitary tumor was removed by craniotomy. Histological examination showed that it was a squamous cell carcinoma metastasis. The patient subsequently underwent whole brain radiotherapy for a total dose of 30 Gy in 10 fractions and conventional external-beam boost irradiation of 10 Gy in 5 fractions to the tumor margins. He remained disease free until 23 months later. He returned to our clinic with left arm paresis after 24 months. In the left parietal lobe a new lesion was determined on his MRI scan. Partial brain reirradiation at a dose of 25 Gy in 10 fractions was performed. There was a partial regression of symptoms after radiotherapy. In the light of this patient, we reviewed the literature and discussed the treatment strategies of patients with solitary brainmetastasis.Öğe The prognostic significance of p21 and Her-2 gene expression and mutation/polymorphism in patients with gastric adenocarcinoma(Humana Press Inc, 2013) Ozen, Alaattin; Kocak, Zafer; Sipahi, Tammam; Oz-Puyan, Fulya; Cakina, Suat; Saynak, Mert; Ibis, CemAnalyses of gene expression status and genetic polymorphisms are methods to identify novel histopathological prognostic factors. In patients with gastric cancer, some cell cycle regulators p53, p21, p27 and Her-2 oncogene have been proposed as prognostic factors. We aimed to investigate the expression and mutation/polymorphism of p21 and Her-2 and also relationship between that genes status and histopathological factors and prognosis in patients with gastric cancer. Forty-four patients with locally advanced gastric cancer were analyzed in this study from January 2000 to December 2008. Clinicopathological parameters, expression and mutation/polymorphism of p21 and Her-2 results were used to predict disease-free survival and overall survival. The positive expression of p21 and Her-2 was observed in 61.4 % (n = 27) and 9.1 % (n = 4) of all 44 tumors, respectively. p21 gene mutation and Her-2 gene polymorphism were detected in 20 % (n = 11) and 2.3 % (n = 1, II phenotype) of cases, respectively. The negative expression of p21 was correlated significantly with diffuse and undifferential type histologies, whole gastric involvement and positive vascular/neural invasion. The median survival rate of patients with negative expression was significantly poorer than that of patients with positive expression of p21 (17 vs. 27 months, p = 0.01, cox regression). p21 mutation was significantly higher in patients with diffuse (p = 0.03) and undifferential (p = 0.02) type histologies. There was no statistically significant association between histopathological parameters and Her-2 gene polymorphism/expression. The negative expression of p21 correlates with disease survival and may be a poor prognostic factor in patients with resected gastric cancer treated with adjuvant chemotherapy.Öğe THE PROGNOSTIC SIGNIFICANCE OF P21 AND HER-2 GENE EXPRESSION AND MUTATION/POLYMORPHISM IN PATIENTS WITH GASTRIC CARCINOMA(Oxford Univ Press, 2011) Ozen, Alaattin; Kocak, Zafer; Sipahi, Tammam; Oz-Puyan, Fulya; Cakina, Suat; Saynak, Mert; Ibis, Cem[Abstract Not Available]Öğe The Protective Effect of Amifostine on Radiation-Induced Proctitis: Systemic Versus Topical Application(Galenos Publ House, 2012) Uzal, Cem; Sezer, Atakan; Usta, Ufuk; Sut, Necdet; Ozen, Alaattin; Yagci, Mehmet AllObjective: The aim of the study was to evaluate the radioprotective efficacy of intrarectal administration of amifostine in radiation-induced proctitis compared to intraperitoneal administration. Materials and Methods: Thirty-two Sprague-Dawley rats were randomly divided into four groups: Control (CONT), irradiation alone (RI), intraperitoneal amifostine plus irradiation (IPAMI), and intrarectal amifostine plus irradiation (IRAMI). The rats in the RI, IPAMI and IRAMI groups were irradiated individually with a single dose of 17.5 Gy to the pelvis. Amifostine was administered by the intraperitoneal (200 mg/kg) or intrarectal (2000 mg/kg) route before irradiation. Histopathologic analysis of the rectum was performed 14 days after irradiation. Results: Significant radiation damage appeared in all histopathologic parameters and was reduced by amifostine. Pretreatment with IPAMI significantly reduced the inflammatory infiltrate in the lamina propria (p=0.021), cryptitis (p=0.002) and crypt abscess (p=0.015). However, the protective effect of IRAMI was significant for all parameters with equal or higher significance than IPAMI, including the eosinophil leucocytes count (p=0.02), and distortion of the crypts (p=0.008), and was also significant for regenerative/reparative atypia (p=0.013). Conclusion: Intrarectal high dose topical administration of amifostine is more effective in the prevention of radiation-induced proctitis compared to its intraperitoneal systemic administration.Öğe Radiation-induced chronic oxidative renal damage can be reduced by amifostine(Humana Press Inc, 2012) Cosar, Rusen; Yurut-Caloglu, Vuslat; Eskiocak, Sevgi; Ozen, Alaattin; Altaner, Semsi; Ibis, Kamuran; Turan, NesrinIn the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3-4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann-Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.Öğe Recurrence Patterns in NSCLC Patients Treated with Post-operative Radiotherapy; Turkish Radiation Oncology Society Thoracic Oncology Group Study(Kare Publ, 2023) Oner Dincbas, Fazilet; Ozen, Alaattin; Korkmaz Kirakli, Esra; Akyurek, Serap; Sert, Fatma; Karabulut Gul, Sule; Benli Yavuz, BerrinOBJECTIVE Post-operative radiotherapy (PORT) in non-small cell lung cancer (NSCLC), especially after complete resection, has long been an unresolved dilemma and debated among therapeutic disciplines. We aimed to evaluate the effects of different radiotherapy volumes and techniques on local-regional recurrence patterns and PORT results in patients with NSCLC. METHODS The results of 389 patients who underwent surgery and received PORT at 11 centers were analyzed retrospectively. The surgical margin was positive or closes in 100 (26%) patients. The PORT dose was a median of 50 Gy (36-60 Gy). Intensity-modulated RT methods were used in 68 (17.5%) patients. RESULTS The first recurrence of the patients who developed relapse, local recurrence was found in 77 (19.8%) patients, distant recurrence was found in 95 (24%) patients, and both recurrences was found in 30 (8%) patients. The median time to locoregional relapse was 14 months (1.84-59.7 months). Local-regional recurrence was not significantly higher in patients with positive surgical margins than in negative pa-tients (39% vs. 29%, p=0.1), but the dose administered to these patients was also higher. Mediastinal recurrence occurred in 28 (19%) patients who did not receive radiotherapy to the mediastinum; 25 of these recurrences (89%) were just near or outside the field. Cardiac events became 7% in all groups and did not change according to chosen mediastinal radiotherapy volume. CONCLUSION A clear description of the PORT volumes according to the localization of the primary tumor and the involved lymph nodes would be beneficial in terms of establishing the recurrence/toxicity balance better.Öğe Relationship between cyclin D1 (A870G) gene polymorphism and lung cancer(Natl Inst Science Communication-Niscair, 2013) Cakina, Suat; Gulyasar, Tevfik; Ozen, Alaattin; Sipahi, Tammam; Kocak, Zafer; Sener, SeralpThe roles of many genes in the pathophysiology of lung cancer have been investigated in different studies. Cyclin D1 (CCND1) gene plays a significant role in the transition from G1 to S phase of the cell cycle and in the phosphorylation of retinoblastoma tumor suppressor protein. In this study, we aimed to identify the relationship between CCND1 A870G gene polymorphism with lung cancer. CCND1 A870G genotypes were determined in 75 patients with lung cancer and in 65 control subjects. DNA was isolated from blood samples and then CCND1 A870G gene polymorphism was identified using PCR and RFLP assay. The distribution of CCND1 A870G polymorphism did not show any significant differences in all lung cancer patients and controls. There was no correlation between CCND1 A870G polymorphism and histopathological findings. However, the AA + AG genotype was significantly higher in metastatic patients, when compared with non-metastatic patients. Thus, the results show that CCND1 gene polymorphism may be a predictor for detecting patients with poor survival who having metastatic disease.Öğe Trimodality treatment in patients with superior sulcus tumors: hopes and realities(Sage Publications Ltd, 2011) Kocak, Zafer; Saynak, Mert; Uygun, Kazim; Yoruk, Yener; Ozen, Alaattin; Sut, Necdet; Altiay, GundenizAims and background. In late 2001 at our institution, we started offering induction radiochemotherapy as a treatment option for superior sulcus tumors. Our aim was to evaluate treatment choices and outcome in this patient group treated over the past 7 years at our institution. Methods. The records of 34 patients were retrospectively reviewed and 33 were assessable for the analysis. Results. Twenty of 28 patients with MO disease had operable disease. The induction radiochemotherapy for superior sulcus tumors was possible in about two-thirds (14/20) of the cases with operable disease, with only one-third (5/14) of these having undergone surgery. The most common reason for not proceeding to surgery following induction radiochemotherapy was patient refusal (n = 5). The median follow-up of all 33 patients was 17 months. In curatively treated patients with (n = 11) or without surgery (n = 15), the median overall survival time was 26 months (range, 10-26) and 26 months (range, 7-71), respectively (P = 0.534). Local-regional and/or distant failure developed in 20 of 26 patients treated curatively. In patients treated with the trimodality regimen (n = 5), no local-regional failure was observed, and distant failure occurred in one case. Conclusions. The trimodality treatment was possible in 25% of cases with operable disease due to the high rate of patient refusal to proceed to surgery following induction radiochemotherapy. No difference in survival was observed between patients treated with surgery and those treated with radiochemotherapy only because of a limited follow-up. So, the benefit of additional surgery is not clear, and a longer follow-up is needed before final conclusions can be drawn.