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Öğe Assessment of Prognostic Factors in Epithelial Ovarian Cancer(Kare Publ, 2017) Onal, Yilmaz; Kostek, Osman; Hacioglu, Muhammet Bekir; Erdogan, Bulent; Kodaz, Hilmi; Bekmez, Esma Turkmen; Hacibekiroglu, IlhanObjectives: Ovarian cancer is the second most common gynecological cancer, and has a 5-year survival rate of about 40% to 45%. This ratio ranges from 15% to 95%, based on prognostic factors. There are numerous clinical, pathological and biological factors related to prognosis. The aim of this study was to assess prognostic factors in advanced epithelial ovarian cancer. Methods: A total of 119 stage III and stage IV ovarian cancer patients were evaluated. The patients age, menopausal status, age of menarche, number of children, height and weight values, surgery, tumor histopathological features, presence of metastasis, residual tumor volume, presence of ascites, abdominal lavage cytology, chemotherapy regimen, number of chemotherapy cycles, the first and last chemotherapy dates, relapse, and recent status were evaluated. Results: The median age of the study patients was 54 years (minimum: 34, maximum: 79 years). The pathological stages were 10 (8.6%) patients with IIIA, 6 (5%) patients with IIIB, 76 (63.9%) patients with IIIC, and 27 (22.7%) patients with stage IV. In multivariate analysis, age of diagnosis (hazard ratio [HR]: 0.44; 95% confidence interval [CI], 0.22-087; p=0.01), postoperative tumor residual status (HR: 0.32; 95% CI, 0.14-0.71; p<0.01), number of adjuvant chemotherapies (HR: 0.48; 95% CI, 0.23-0.98; p=0.04), and platinum sensitivity (HR: 0.37; 95% CI, 0.18-0.74; p<0.01) were found to be independent variables related to longer survival. Notably, a patient treated with more than 6 cycles of chemotherapy had a worse prognosis. Conclusion: Independent indicators of a poor prognosis in our study were determined to be advanced age at diagnosis, a residual tumor more than 2 cm in size, more than 6 cycles of chemotherapy, and the presence of platinum-resistant disease. A multidisciplinary approach is needed to improve prognosis.Öğe The Association Between Corrected QT Dispersion and Iron Parameters in Hemodialysis Diseases(Kare Publ, 2017) Erdogan, Bulent; Erdogan, Zerrin Ozturk; Savli, HalukObjectives: Anemia is one of the most common complications to occur in hemodialysis patients. Blood transfusions to correct anemia can result in iron accumulation in the parenchymal tissues. Iron accumulation in the heart leads to fibrosis in the myocardium. The aim of this study was to determine the association between corrected QT dispersion (QTcd) and serum iron parameters in patients with end-stage renal disease. Methods: A total of 80 subjects (60 patients and 20 healthy) were enrolled in the study. Patients were receiving hemodialysis treatment 3 times a week with regular erythropoietin and iron replacement at least once a year. Patients with cardiac insufficiency; diabetes mellitus; ischemic heart disease diagnosed with effort test or coronary angiography; any acute infectious disease; branch block on electrocardiogram (ECG); arrhythmia, such as atrial fibrillation, bradycardia, or tachycardia; patients using any drug that affects QT interval; and patients with electrolyte disturbances were excluded. Blood sample was taken and ECG recordings were made 1 day after routine hemodialysis to ensure that the patient's laboratory tests and ECG parameters were not affected by acute metabolic effects of dialysis. Patients whose corrected QT (QTc) interval was calculated in at least 9 derivations were included in the study. QTcd was measured by calculating the difference between the longest QTc interval and the shortest QTc interval. Results: The hematocrit and hemoglobin levels of patients were statistically lower than those of the control group (p<0.05 for both). Serum iron level and percent transferrin saturation index were similar between groups. Ferritin level of the patients was statistically higher than the ferritin level of the control group (p<0.01). On the other hand, the total iron binding capacity level of the patient group was statistically significantly lower compared with the total iron binding capacity level of the control group (p<0.01). The longest QT interval of the patients was statistically significantly longer compared with the control group (p<0.01).There was no statistically significant difference between the 2 groups with normal and longer corrected QT dispersion (QTcd) in terms of dialysis duration or age (p>0.05). QTcd was not significantly correlated with age, duration of dialysis, calcium, potassium, iron, or ferritin level (p>0.05 for all). A statistically significant correlation was only found between QTcd and transferrin saturation index (r=0.254; p<0.05). Conclusion: The hemodialysis patients had a longer QTcd compared with individuals with normal renal function in our study. A positive correlation was detected between the transferrin saturation index and QTcd. Iron replacement therapy should be administered more carefully and reduced iron concentration and transferrin saturation index should be targeted in hemodialysis patients with QTcd longer than 50 milliseconds.Öğe Association between specific KRAS mutations and the clinicopathological characteristics of colorectal tumors(Spandidos Publ Ltd, 2015) Kodaz, Hilmi; Hacibekiroglu, Ilhan; Erdogan, Bulent; Turkmen, Esma; Tozkir, Hilmi; Albayrak, Dogan; Uzunoglu, SernazThe aim of this study was to investigate the clinicopathological characteristics and distribution by tumor localization of KRAS point mutations in metastatic colorectal cancer. A total of 189 patients diagnosed with colorectal cancer between 2007 and 2014, who were either metastatic at the time of diagnosis or developed metastasis subsequently, were included in this study. KRAS mutation analysis was performed in the primary tumor tissues and KRAS mutations were identified in 47.6% of the patients. There was a high frequency of the p.G13D point mutation in left-colon tumors (P=0.011), while the p.G12D point mutation was more frequent in right-colon tumors (P=0.004). KRAS wild-type frequency (P=0.02) was higher among patients aged <40 years. A comparison of codon 12 and 13 mutations revealed that codon 12 mutations were more common in the >50-year-old group (P=0.03) and codon 13 mutations were more common in the <70-year-old group (P=0.04). KRAS wild-type tumors were localized in the right colon (P=0.005) and tumors with the p.G13D point mutation (P=0.018) were diagnosed at non-metastatic stages. In conclusion, KRAS point mutations in colorectal cancer exhibited a heterogeneous distribution in terms of tumor localization. In addition, the p.G13D point mutation was found to differ from other mutations in several aspects.Öğe Carnitine or dimethyl sulfoxide, or both, for the treatment of anthracycline extravasation in rats(Informa Healthcare, 2013) Uzunoglu, Sernaz; Cosar, Rusen; Cicin, Irfan; Ibis, Kamuran; Demiralay, Ebru; Benlier, Erol; Erdogan, BulentThis study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200-225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.Öğe A case of Guillain-Barre syndrome in a patient with small cell lung cancer treated with chemotherapy(Kare Publ, 2014) Turkmen, Esma; Erdogan, Bulent; Hacibekiroglu, Ilhan; Kodaz, Hilmi; Uzunoglu, Sernaz; Celik, Yahya; Cicin, IrfanGuillain-Barre syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy characterized by bilateral progressive symmetrical paralysis. GBS is rarely seen neuropathy in cancer patients. In the literature some cases of GBS associated with anticancer chemotherapy. In this case; the guillain-barre syndrome developed after the treatment of a 59-year-old male patient with metastatic small cell lung carcinoma who admitted to hospital with neutropenic fever after cisplatin/etoposide chemoteraphy regime is presented. The patients complained of bilteral progressive symmetrical paralysis in upper and lower limbs with depressed deep tendon reflexes and hypoesthesia. There was no pathological findings on electromyography. There was no a sign at radiological imaging that explained cranial and spinal mestastasis. The cerebrospinal fluid had albuminocytologic dissociation. Decline in tumoral lesions were detected on chest radiography. Accompanied by clinical and laboratory findings, a diagnosis of Guillain-Barre syndrome was considered. Semptoms completely disapperared after intravenous immunoglobulin for five days. Recurrence did not during follow-up. The patients was administered a total of 4 cycles of cisplatin/etoposide chemotherapy. The patient died due to disease progression six months later. We think that, in this case GBS was not a paraneoplatic syndrome because there was more than 50% tumor shrinkage. We propose GBS was induced by infection and chemotherapy rather than malignancy.Öğe Clinical features of the patient with multiple primary tumors: Single center experience(Kare Publ, 2017) Gokyer, Ali; Kostek, Osman; Hacioglu, Muhammet Bekir; Erdogan, Bulent; Kodaz, Hilmi; Turkmen, Esma; Hacibekiroglu, IlhanOBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated. This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung-larynx and lung-colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung-bladder, lung-larynx, breast-endometrium, and breast-colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous secondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival, although they were not statistically significant.Öğe Combination of Docetaxel and Gemcitabine Ineffective in Metastatic Eccrine Porocarcinoma: A Case Report(Kare Publ, 2017) Kodaz, Hilmi; Hacioglu, Muhammet Bekir; Kostek, Osman; Erdogan, Bulent; Tastekin, Ebru; Kodaz, Cagnur Elpen; Cicin, IrfanMalignant eccrine porocarcinoma is a very rare tumor and the etiology is not known. Treatment is surgical removal of the tumor. The benefit of chemotherapy and radiotherapy is unclear. A 49-year-old male patient presented with the complaint of left inguinal swelling. Ultrasonography examination revealed 5x4 cm inguinal lymphadenopathy. The inguinal lymph nodes were excised. Pathology report indicated eccrine porocarcinoma. The patient was treated with cisplatin 40 mg/m(2) week as well as concurrent radiotherapy for 5 weeks. After 6 weeks of dual therapy, liver metastases were detected. KRAS, NRAS, and BRAF tests were negative. Gemcitabine was administered at a dose of 1000 mg/m(2) on days 1 and 8 every 21 days, and docetaxel was administered at a dose of 75 mg/m(2) on day 8, every 21 days. There was progression after 2 cycles of chemotherapy. The patient lived 7 months. In this case, use of synchronous cisplatin and radiotherapy as adjuvant treatment could not prevent tumor metastasis. The combination chemotherapy of docetaxel and gemcitabine applied after metastatic disease development was ineffective.Öğe Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer(Spandidos Publ Ltd, 2015) Hacibekiroglu, Ilhan; Kodaz, Hilmi; Erdogan, Bulent; Turkmen, Esma; Esenkaya, Asim; Onal, Yilmaz; Uzunoglu, SernazThe aim of this study was to retrospectively compare the efficacy and toxicity of the oxaliplatin + 5-fluorouracil (5-FU) + leucovorin (LV) regimen [modified (m) FOLFOX-6] with that of the docetaxel + cisplatin + 5-FU regimen (DCF) in patients with advanced gastric cancer (AGC). A total of 72 patients received DCF (75 mg/m(2) docetaxel and 75 mg/m(2) cisplatin on day 1 and 750 mg/m(2) 5-FU on days 1-5) every 21 days, whereas 54 patients received mFOLFOX-6 (85 mg/m(2) oxaliplatin and 400 mg/m(2) LV as a 2-h infusion, followed by a 5-FU bolus of 400 mg/m(2) and 2,400 mg/m(2) 5-FU as a 46-h continuous infusion) every 14 days. In the DCF arm, 55 (76.4%) of the patients received prophylactic granulocyte colony-stimulating factor (G-CSF), 48-72 h following completion of chemotherapy. The median follow-up of the study was 12.1 months. The overall response rate (ORR) was 37.0% for mFOLFOX-6 and 40.3% for DCF (P=0.72). The median time to progression was 6.5 and 6.2 months in the mFOLFOX-6 and DCF arms, respectively (P=0.70). The median overall survival was 11.4 and 13.5 months in the mFOLFOX-6 and DCF arms, respectively (P=0.72). The rates of hematological toxicity did not differ between the two arms. However, in the subgroup analysis, grade 3-4 neutropenia and febrile neutropenia were significantly more common among patients who had not received G-CSF prophylaxis in the DCF arm. The incidence of grade 3-4 nausea/vomiting and diarrhea were significantly higher in the DCF arm. In conclusion, the present study demon-strated that the efficacy of the mFOLFOX-6 regimen was comparable to that of the DCF regimen in AGC patients. In addition, the benefit of G-CSF prophylaxis in conjunction with the DCF regimen was demonstrated.Öğe Enzalutamide in Prostate Cancer, A Review on Enzalutamide and cancer(Kare Publ, 2018) Erdogan, Bulent; Kostek, Osman; Bekirhacioglu, MuhammetProstate carcinoma is androgen-dependent, and therefore the main target of treatment is lowering androgen levels. Medical or surgical castration, androgen receptor-blocking agents, androgen-synthesis inhibitors, chemotherapy, sipuleucel-T, and radium-223 are treatment options. Enzalutamide is a relatively new androgen-signaling inhibitor that has 5 to 8 times greater affinity for the androgen receptor ( AR) than bicalutamide. Enzalutamide does not demonstrate agonistic activity on ARs. Enzalutamide induces apoptosis of prostate cancer cells. Enzalutamide is effective in metastatic castration-resistant prostate cancer in patients with progression after docetaxel treatment and in chemotherapy-naive patients. Enzalutamide is also superior to the commonly used AR blocking agent bicalutamide in chemotherapy-naive metastatic and non-metastatic castration-resistant prostate cancer patients. Its efficacy has been proven in hormonenaive patients, and several trials are ongoing. Enzalutamide has a favorable side effect profile and improves quality of life and pain scores. There are ongoing studies examining the efficacy and safety of enzalutamide on other several AR-expressing tumors.Öğe Frequency of RAS Mutations (KRAS, NRAS, HRAS) in Human Solid Cancer(Kare Publ, 2017) Kodaz, Hilmi; Kostek, Osman; Hacioglu, Muhammet Bekir; Erdogan, Bulent; Kodaz, Cagnur Elpen; Hacibekiroglu, Ilhan; Turkmen, EsmaRAS oncogene affects numerous cellular functions including growth, proliferation, apoptosis, migration, division and differentiation of the cells. It has 3 known isoforms as Harvey- RAS (HRAS), Kirsten - RAS (KRAS) and Neuroblastoma-RAS (NRAS). RAS has an intrinsic GTPase activity. It encodes proteins binding the guanine nucleotides. KRAS and HRAS were discovered in studies carried out on viruses leading to cancer. Retroviral oncogenes related to murine sarcoma virus genes (Kristen Rat Sarcoma Virus and Murine Sarcoma Virus) were discovered in 1982. These two oncogenes are similar to human KRAS. Approximately 30% of all human cancers have ras genes. Mutations in KRAS account for about 85% for all RAS mutations in human tumors, NRAS is about 11-15%, and HRAS is about 1%.Öğe Impact of active smoking on survival of patients with metastatic lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) mutation(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2016) Erdogan, Bulent; Kodaz, Hilmi; Karabulut, Senem; Cinkaya, Ahmet; Tozkir, Hilmi; Tanriverdi, Ozgur; Cabuk, DevrimLung cancer in smokers and non-smokers demonstrates distinct genetic profiles, and cigarette smoking affects epidermal growth factor receptor (EGFR) function and causes secondary EGFR tyrosine kinase resistance. We evaluated the effect of active smoking in patients with metastatic lung adenocarcinoma. A total of 132 metastatic lung adenocarcinoma patients, diagnosed between 2008 and 2013, with known EGFR mutation status, were evaluated retrospectively. Among these patients, 40 had an activating EGFR mutation. Patients who continued smoking during the treatment were defined as active smokers. Former smokers and never smokers were together defined as non-smokers. The outcomes of the treatment in relation to the EGFR mutation and smoking status were evaluated. The median follow-up time was 10.5 months. The overall response rate for the first-line therapy was significantly higher among the EGFR-mutant patients (p = 0.01), however, smoking status had no impact on the response rate (p = 0.1). The EGFR-mutant active smokers progressed earlier than the non-smokers (p < 0.01). The overall survival (OS) of the non-smokers and patients treated with erlotinib was significantly longer (p = 0.02 and p = 0.01, respectively). Smoking status did not affect the OS in EGFR wild type tumors (p = 0.49) but EGFR-mutant non-smokers had a longer OS than the active smokers (p = 0.01). The active smokers treated with erlotinib had poorer survival than the non-smokers (p = 0.03). Multivariate analysis of EGFR-mutant patients showed that erlotinib treatment at any line and non-smoking were independent prognostic factors for the OS (p = 0.04 and p = 0.01, respectively). Smoking during treatment is a negative prognostic factor in metastatic lung adenocarcinoma with an EGFR mutation.Öğe Impact of bevacizumab on survival outcomes in primary tumor resected metastatic colorectal cancer(Humana Press Inc, 2015) Kodaz, Hilmi; Erdogan, Bulent; Hacibekiroglu, Ilhan; Turkmen, Esma; Gurkan, Hakan; Albayrak, Dogan; Tastekin, EbruWe have studied the efficacy of bevacizumab in colorectal cancer with unresectable metastasis patients who had undergone resection of primary tumor. The patients with unresectable metastasis during diagnosis who had undergone resection of primary tumor without chemotherapy and the patients without resection of primary tumor were included. Among patients who had met the inclusion criteria, 46 patients with resection of primary tumor and 47 without resection of primary tumor were included in the study. A total of 93 unresectable metastatic colorectal cancer patients were included in the study. Median PFS was 9 months (95 % CI 7.37-10.62) in patients with resected primary tumor and bevacizumab containing first-line chemotherapy combination. Median PFS was 10 months (95 % CI 8.06-11.93) in patients without bevacizumab (P = 0.66) Median OS was 25 months (95 % CI 17.92-32.07) in patients with resected primary tumor and bevacizumab containing first-line chemotherapy combination. Median OS was 16 months (95 % CI 9.71-22.28) in patients without bevacizumab (P = 0.36) Median OS was 16 months (95 % CI 13.06-8.939) in patients without resected primary tumor and bevacizumab containing first-line chemotherapy combination. Median OS was 9 months (95 % CI 1.48-16.51) in patients without bevacizumab (P = 0.012). Bevacizumab seems ineffective in mCRC patients with resected primary tumor. An increase in number of retrospective literature data and randomized, prospective studies is required about this subject.Öğe Importance of Ki-67 in human epidermal growth factor receptor 2 positive breast cancer(Imprimatur Publications, 2015) Erdogan, Bulent; Turkmen, Esma; Yalta, Tulin Deniz; Usta, Ufuk; Kodaz, Hilmi; Hacibekiroglu, Ilhan; Tanriverdi, OzgurPurpose: The aim of this study was to evaluate the importance of Ki-67 in Human Epidermal Growth Factor Receptor 2 (Her-2) positive breast cancer patients. Methods: We reviewed the records of patients diagnosed with Her-2-positive non-metastatic breast cancer between 2005 and 2011. Paraffin-embedded tissue samples were stained with MIB-1 mouse monoclonal antibody to find Ki-67 levels. Patients were grouped as low Ki-67 <20% and high Ki-67 >= 20%. Demographic and clinical features were compared. Results: One hundred and six patients were included in the study. Median follow up time was 41 months (range 15-100). Median age was 49.5 years (range 29-79). Twenty-nine patients (27.4%) were in the Ki-67 low group. Demographic features were similar in both groups. Lymphovascular invasion was more frequent in the Ki-67 high group, and hormone receptor (HR) positivity was more frequent in the Ki-67 low group (p=0.03, p=0.03, respectively). Recurrence rate was not significantly different in both groups (p=0.36). T stage (p=0.02), stage (p<0.01), lymphovascular invasion (p=0.02), ER status (p=0.02), and HR status (p<0.01) were related with recurrence. In multivariate analysis, stage and HR negativity were independent factors for recurrence (p<0.01, p=0.01, respectively). Recurrence sites were also similar in both groups. Survival rates at the third year for Ki-67 low group and Ki-67 high group were 94% and 92%, respectively. Conclusion: Her-2 positive patients with low Ki-67 and high Ki-67 had similar demographic and pathologic features except lymphovascular invasion and HR status. HR status was an important factor for disease course. Clinical course was determined by HR status rather than Ki-67.Öğe Incidence of contrast-induced nephropathy in hospitalised patients with cancer(Springer, 2014) Cicin, Irfan; Erdogan, Bulent; Gulsen, Emrah; Uzunoglu, Sernaz; Sut, Necdet; Turkmen, Esma; Kodaz, HilmiObjectives To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. Methods Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. Results CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P=0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P=0.005); it was also an independent risk factor (P=0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P=0.021) and in patients with hypertension (P=0.044). Conclusions The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. Key Points Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. CIN occurs more often when CT is performed <45 days after chemotherapy. Hypertension and treatment with bevacizumab appear to be additional risk factors.Öğe Increased dose single-agent gemcitabine in platinum-taxane resistant metastatic ovarian cancer(Sage Publications Ltd, 2015) Kodaz, Hilmi; Hacibekiroglu, Ilhan; Turkmen, Esma; Erdogan, Bulent; Elpen, Cagnur; Uzunoglu, Sernaz; Cicin, IrfanBackground: In platinum-taxane resistant epithelial ovarian cancer (EOC), we aimed to determine the effectiveness. Patients and Methods: Between 2004 and 2013, patients afflicted with platinum-taxane resistant EOC and who were administered a 30-minute i.v. infusion of single-agent gemcitabine at a dose of 1,250 mg/m(2) on the 1st, 8th and 15th days, every 28 days, were examined retrospectively. Results: Twenty-six patients with platinum-taxane resistant EOC were included in the study. The overall survival (OS) was 48 months. The median survival after becoming platinum-taxane resistant was 16 months for the study population. Median time to progression (TTP) and median survival after becoming platinum-taxane resistant for patients who received second-line treatment were 3.3 months and 16 months, respectively; for patients who received third-line treatment with gemcitabine, these were 3.7 months and 19 months, respectively. Administration of gemcitabine as second- and third-line chemotherapy in platinum-taxane resistant EOC, provides similar TTP and OS outcomes (p = 0.4, p = 0.9) with a similar response and toxicity rate. Conclusions: Second- and third-line gemcitabine at a dose of 1,250 mg/m(2) on days 1 , 8 and 15 every 28 days as a 30-minute i.v. infusion in platinum-taxane resistant EOC is an effective treatment option with a tolerable and manageable toxicity.Öğe Is the Charlson Comorbidity Index a Prognostic Indicator for Toxicity and Mortality in Elderly Patients with Locally Advanced Rectal Cancer?(Acad Medical Sciences I R Iran, 2019) Kostek, Osman; Bozkaya, Yakup; Hacioglu, Muhammet Bekir; Ozdemir, Nuriye Yildirim; Yilmaz, Erdem; Demircan, Nazim Can; Erdogan, BulentBackground: Aging is significantly related to multiple comorbidities. Even with a good performance score, some elderly patients may have poor survival outcomes. We aimed to evaluate the prognostic value of the Charlson comorbidity index (CCI) for mortality and toxicity in elderly patients with locally advanced rectal cancer (LARC). Methods: Seventy-two elderly patients with LARC who were treated with neoadjuvant chemoradiotherapy (CRT) were included. Based on their CCI score, severity of the comorbidity was categorized into 2 groups: CCI<7 and CCI >= 7. Results: The overall survival (OS) at 5 years was 54.4 percent in patients treated with neoadjuvant CRT. Median OS was not reached for all patients as well as patients with CCI score <7, but median OS was 25 (95% CI 1.0-62.1) months in patients with CCI >= 7 (P=0.002). The OS at 2 years was 79.1 percent in the patients with CCI <7 and 50.0 percent in the patients with CCI score >= 7 (P=0.002). Moreover, there was a trend toward, patients with higher CCI score who had more treatment related to grade 3 or 4 toxicity compared to those with CCI score <7 (33.3% vs 13.3%, respectively, P=0.09). Multivariable analysis indicated that the CCI score=7, presence of down-staging after therapy and clinical stage (III) independently predict mortality (HR 6.14, 95% CI 2.45-15.35, P<0.001) in patients with LARC. Conclusion: Although CCI score was not significantly associated with both toxicity and disease-free survival (DFS), we suggest that baseline CCI score might be a valuable prognostic indicator for physicians to evaluate elderly patiens with LARC for optimal treatment.Öğe K-RAS and N-RAS mutations in testicular germ cell tumors(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2017) Hacioglu, Bekir Muhammet; Kodaz, Hilmi; Erdogan, Bulent; Cinkaya, Ahmet; Tastekin, Ebru; Hacibekiroglu, Ilhan; Turkmen, EsmaTesticular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs) are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS) gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55%) pure seminoma cases and 19 (45%) non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen). In total, a RAS mutation was present in 12 patients (27%): 7 seminoma (29%) and 5 non-seminoma cases (26%) [p = 0.55]. AK-RAS mutation was present in 4 pure seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16%) and 3 non-seminoma tumors (15%) [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: One with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.Öğe Major and minor salivary gland cancers: A multicenter retrospective study(Wiley, 2023) Hacioglu, Muhammet Bekir; Erdogan, Bulent; Bardakci, Murat; Algin, Efnan; Gulbagci, Burcu; Hacibekiroglu, Ilhan; Hamdard, JamshidBackgroundMost of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. MethodsA total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. ResultsThe study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). ConclusionsEpidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.Öğe Medical Treatment of Breast Cancer Bone Metastasis: From Bisphosphonates to Targeted Drugs(Asian Pacific Organization Cancer Prevention, 2014) Erdogan, Bulent; Cicin, IrfanBreast cancer bone metastasis causing severe morbidity is commonly encountered in daily clinical practice. It causes pain, pathologic fractures, spinal cord and other nerve compression syndromes and life threatening hypercalcemia. Breast cancer metastasizes to bone through complicated steps in which numerous molecules play roles. Metastatic cells disrupt normal bone turnover and create a vicious cycle to which treatment efforts should be directed. Bisphosphonates have been used safely for more than two decades. As a group they delay time to first skeletal related event and reduce pain, but do not prevent development of bone metastasis in patients with no bone metastasis, and also do not prolong survival. The receptor activator for nuclear factor kappa B ligand inhibitor denosumab delays time to first skeletal related event and reduces the skeletal morbidity rate. Radionuclides are another treatment option for bone pain. New targeted therapies and radionuclides are still under investigation. In this review we will focus on mechanisms of bone metastasis and its medical treatment in breast cancer patients.Öğe Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer(Mdpi, 2023) Gokmen, Ivo; Tastekin, Ebru; Demir, Nazan; Ozcan, Erkan; Akgul, Fahri; Hacioglu, Muhammed Bekir; Erdogan, BulentThe aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients' demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAF(V600E) (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAF(V600E) and BRAF(non-V600E) and their analysis according to specific tumor localizations showed that all four BRAF(non-V600E) mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.
