PubMed İndeksli Yayınlar Koleksiyonu
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Item Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study(2022) Ferrandiz-Pulido, C.; Gomez-Tomas, A.; Llombart, B.; Mendoza, D.; Marcoval, J.; Piaserico, S.; Baykal, C.; Bouwes-Bavinck, J.N.; Racz, E.; Kanitakis, J.; Harwood, C.A.; Cetkovska, P.; Geusau, A.; Del Marmol, V; Masferrer, E.; Cano, C.Orte; Ricar, J.; de Oliveira, W.R.; Salido-Vallejo, R.; Ducroux, E.; Gkini, M.A.; Lopez-Guerrero, J.A.; Kutzner, H.; Kempf, W.; Seckin, D.; 35607918Background The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. Objective To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. Methods Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. Results A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. Limitations Retrospective design and heterogeneity of SOTR cohort. Conclusions MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.Item In reply to Shih YJ et.al. (doi: 10.1111/odi.14349)(2022) Topkan, Erkan; Somay, Efsun; Yilmaz, Busra; 0000-0001-8120-7123; 0000-0003-0633-5648; 36114821; AAG-2213-2021Item Prognostic Value of Pretreatment Systemic Immune-Inflammation Index in Glioblastoma Multiforme Patients Undergoing Postneurosurgical Radiotherapy Plus Concurrent and Adjuvant Temozolomide(2020) Topkan, Erkan; Besen, Ali Ayberk; Ozdemir, Yurday; Kucuk, Ahmet; Mertsoylu, Huseyin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0002-2218-2074; 0000-0001-8120-7123; 0000-0002-7862-0192; 32565725; M-9530-2014; AAG-5629-2021; AAG-2213-2021; AAD-6910-2021Objectives. To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide. Methods. The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII=plateletsxneutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group. Results. A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII<565; n=71) and high-SII (SII >= 565; n=96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; P<0.001) and OS (11.1 versus 22.9 months; P<0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS (P<0.001) and OS (P<0.001) further retained its independent significance in multivariate analysis, as well. Conclusions. The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.Item Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study(2020) Topkan, Erkan; Ozdemir, Yurday; Guler, Ozan Cem; Kucuk, Ahmet; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezen, Duygu; Akdemir, Eyub Yasar; Sezer, Ahmet; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0001-6908-3412; 0000-0002-2218-2074; 0000-0002-6445-1439; 0000-0001-8120-7123; 0000-0002-7862-0192; 32952557; M-9530-2014; AAC-5654-2020; AAG-5629-2021; AAD-2667-2020; AAG-2213-2021; AAD-6910-2021Background. We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT).Methods. Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups.Results. The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%;P=0.52) and median overall survival (25.2 versus 24.6 months;P=0.69), locoregional progression-free survival (15.3 versus 15.1 months;P=0.52), and progression-free survival (11.7 versus 11.2 months;P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P<0.001) were all significantly higher in the ENI than in the IFRT group, respectively.Conclusion. Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.Item The effect of helicobacter pylori eradication on atrophic gastritis and intestinal metaplasia : a retrospective single center research(2020) Suna, N.; Etik, D.; Ocal, S.; Gunduz, C.; Acikgoz, A.; Bildik, I; Gursoy, A.; Kasgoz, I; Tuleylioglu, H.; Boyacioglu, A.; 0000-0003-3719-9482; 0000-0002-4724-0728; 0000-0001-6234-7788; 33094583; ABH-4817-2020; AAJ-4707-2021; AAI-8822-2021Background and study aims : Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide. Helicobacter pylori (Hp) plays an important role in gastric carcinogenesis by inducing precancerous changes such as atrophic gastritis (AG) and intestinal metaplasia (IM). In our study, we aim to compare the grade of AG and IM before and after Hp eradication in patients who underwent esophagogastroduodenoscopy (EGD) in our center. Patients and methods : The data of 40.060 patients who underwent EGD for various reasons in our Endoscopy Unit between June 2011 and November 2017 were retrospectively evaluated. The grade of AG and IM before and after Hp eradication of patients meeting the study criteria were compared with each other. In addition, these findings were compared using OLGA and OLGIM staging systems. Results : A total of 175 patients, 89 (50.9%) women and 86 (49.1%) men, were included in the study. The mean age was 55 +/- 12 years. The mean time between two EGD examinations was 38 +/- 14 months. Significant improvement was observed in the grade of AG on corpus and antrum after Hp eradication (P=0.000, P=0.008). In the corpus and antrum, the grade of IM was regressed but this was not significant (P=0.80 and P=0.370 respectively). There was a decrease in OLGA stages after Hp eradication (P=0.000). There was also a reduction in the OLGIM stages, but this was not significant(P=0.341). Conclusion: Our study demonstrates that Hp eradication may reduce the risk of developing GC by providing an improvement in AG and IM which are precancerous changes in GC.Item Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol(2020) Topkan, Erkan; Kucuk, Ahmet; Ozdemir, Yurday; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezen, Duygu; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-7862-0192; 0000-0001-8120-7123; 0000-0002-2218-2074; 0000-0002-1932-9784; 33274245; AAD-6910-2021; AAG-2213-2021; AAG-5629-2021; M-9530-2014Objectives. We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. Methods. The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI=NeutrophilsxMonocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. Results. The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI <= 1.78 (N=96) and SIRI>1.78 (N=85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI <= 1.78 cohort had altogether significantly superior median PFS (16.2 versus 6.6 months; P<0.001) and OS (22.9 versus 12.2 months; P<0.001) than its SIRI>1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (P<0.001) and OS (P<0.001) durations, respectively. Conclusions. Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.Item Significance of overall concurrent chemoradiotherapy duration on survival outcomes of stage IIIB/C non-small-cell lung carcinoma patients: Analysis of 956 patients(2019) Topkan, Erkan; Ozdemir, Yurday; Kucuk, Ahmet; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezer, Ahmet; Selek, Ugur; 31329602Background To investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT) Methods The study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes. Results The ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD >= 50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD >= 50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus >= 2 cm), and 2-3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes. Conclusions Longer ORTD beyond >= 50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative.Item Therapeutic Potential of Apigenin, a Plant Flavonoid, for Imatinib-Sensitive and Resistant Chronic Myeloid Leukemia Cells(2014) Solmaz, Soner; Gokbulut, Aysun Adan; Cincin, Birsu; Ozdogu, Hakan; Boga, Can; Cakmakoglu, Bedia; Kozanoglu, Ilknur; Baran, YusufDespite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.Item Variations in apparent diffusion coefficient values following chemotherapy in pediatric neuroblastoma(2015) Demir, Senay; Altinkaya, Naime; Kocer, Nazim Emrah; Erbay, Ayse; Oguzkurt, Pelin; 25519453PURPOSE In children the assessment of solid tumors' response to chemotherapy is based primarily on size reduction, which can be unreliable and a late marker, in the presence of necrosis. We aimed to establish whether apparent diffusion coefficient (ADC) values of childhood neuroblastomas show proportional changes in relation to chemotherapy response. METHODS We evaluated 15 pediatric patients with abdominopelvic neuroblastomas, who had undergone MRI before and after chemotherapy. Two radiologists retrospectively analyzed all images by drawing a round uniform region-of-interest in the solid/contrast-enhancing portion of the lesions in consensus. The ADC values from pre- and postchemotherapy images were compared. RESULTS Postchemotherapy ADC values were significantly higher than those obtained before treatment (P < 0.05, for minimum, maximum, and median ADC values). CONCLUSION Our results support diffusion-weighted MRI as a promising noninvasive biomarker of therapeutic responses. To the best of our knowledge, this is the first report to compare diffusion-weighted imaging findings before and after chemotherapy in childhood neuroblastic tumors.Item Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study(2017) Seckin, D.; Oh, C.C.; Hofbauer, G.F.L.; Serra, A.L.; Harwood, C.A.; Mitchell, L.; Proby, C.M.; Olasz, E.B.; Mosel, D.D.; Piaserico, S.; Fortina, A.B.; Geusau, A.; Jahn-Bassler, K.; Gerritsen, M. J. P.; Gulec, A.T.; Cetkovska, P.; Ricar, J.; Imko-Walczuk, B.; Debska-Slizien, A.; Bavinck, J. N. Bouwes; 28012178BackgroundOrgan transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. ObjectivesTo investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. MethodsWe followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. ResultsThere was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 16 [95% confidence interval (CI) 097-27], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 17 (95% CI 10-28). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. ConclusionsWe suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.