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    Effect of delayed radical cystectomy for invasive bladder tumors on lymph node positivity, cancer-specific survival and total survival
    (Sage Publicatıons Ltd., 2018) Turk, Hakan; Un, Sitki; Cinkaya, Ahmet; Kodaz, Hilmi; Parvizi, Murtaza; Zorlu, Ferruh
    Introduction: Radical cystectomy (RC) is the main treatment option for patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC), which carry the highest risk of progression. In this study, we investigated the effect of time from transurethral resection of the bladder (TUR-B) to cystectomy on lymph node positivity, cancer-specific survival and overall survival in patients with MIBC. Methods: The records were reviewed of 530 consecutive patients who had RC and pelvic lymphadenectomy procedures with curative intent performed by selected surgeons between May 2005 and April 2016. Our analysis included only patients with transitional cell carcinoma of the bladder; we excluded 23 patients with other types of tumor histology. Results: Patients who underwent delayed RC were compared with patients who were treated with early RC; both groups were similar in terms of age, gender, T stage, tumor grade, tumor differentiation, lymph node status and metastasis status. However, when both groups were compared for disease-free survival and overall survival, patients of the early-RC group had a greater advantage. Conclusions: The optimal time between the last TUR-B and RC is still controversial. A reasonable time for preoperative preparation can be allowed, but long delays, especially those exceeding 3 months, can lead to unfavorable outcomes in cancer control.
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    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, Devrim
    Lung 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.
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    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, Esma
    Testicular 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.
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    Unknown primary adenocarcinomas: A single-center experience
    (Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2016) Uzunoglu, Sernaz; Erdogan, Bulent; Kodaz, Hilmi; Cinkaya, Ahmet; Turkmen, Esma; Hacibekiroglu, Ilhan; Sari, Ali
    This study aimed to elucidate the clinical and prognostic characteristics of a homogeneous group of patients with cancer of unknown primary (CUP). Between 1999 and 2014, CUP was diagnosed in 159 (1.3%) of 11,742 cancer patients at Trakya University Hospital (Edirne, Turkey). Ninety-seven (61%) of the 159 patients were retrospectively reviewed. Among these, 61 (62.8%) patients with adenocarcinoma were included in this study. The most frequently predicted primary tumor site was the lung (37.7%), and 59% of the patients were smokers. There was a significant relationship between smoking and the lung as a potential primary cancer site (p = 0.042). The most frequent site of metastasis was the liver (60.7%). The median number of metastases per patient was two, but patients with liver metastases had a median of five metastases. The overall median survival time was 7 months. Median survival was significantly longer in patients with a predicted primary site than in patients without the predicted site (7 vs. 6 months, respectively; p = 0.038). When the patients with predicted ovarian and peritoneal tumors were excluded from the comparison, the statistical p value was still close to significant (p = 0.07). Multivariate analysis revealed that smoking, liver metastasis, serum alkaline phosphatase = 92 U/L, and progression in response to chemotherapy were independent predictors of a poor prognosis. The present study identified several independent prognostic factors in patients with unknown primary adenocarcinomas who received chemotherapy. Smoking, the presence of liver metastasis, and response to chemotherapy were independent risk factors for both progression-free and overall survival.