Wos İndeksli Yayınlar Koleksiyonu

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    Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
    (2022) Bulutay, Pinar; Haberal, Nihan; Ozen, Ozlem; Erdem, Ozlem; Zeren, Emine H.; Kulac, Ibrahim; Taskiran, Cagatay; Vatansever, Dogan; Ayhan, Ali; Kapucuoglu, Nilgun; 34856570
    Endocervical adenocarcinomas (ECAs) have been recently reclassified according to their morphologic features linked to etiology by the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and this system is adopted by WHO 2020. This classification separates the ECAs as human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) subtypes. According to WHO 2020, high risk (HR)-HPV association can be histologically recognized by the presence of luminal mitoses and apoptosis. Therefore, investigating the reproducibility of the morphologic criteria of this new classification will be important in observing the recognizability of tumor types. Full slide sets of 94 ECAs were collected from 4 institutions in Turkey and reclassified on the basis of IECC/WHO 2020 criteria and the presence or absence of HR-HPV. HR-HPV presence was confirmed by HPV DNA in situ hybridization, p16 immunohistochemistry and in conflicted cases with real time-polymerase chain reaction. The final diagnoses were given based on the combination of the histologic evaluation and ancillary test results. Our cohort consisted of 73.4% HPVA and 26.6% HPVI cases. According to the WHO 2020 criteria 92.7% of HPVAs and 88% of HPVIs were easily classified. HPV DNA in situ hybridization was positive in 91.3% of the HPVAs and p16 was positive in all HPVAs, and also positive in 8% of the HPVIs. In conclusion, most of the ECAs can be diagnosed by their characteristic morphologic features by the WHO 2020 criteria. However, we want to emphasize that mitosis/apoptosis criteria may not be helpful especially in mucinous ECAs and ancillary tests for HR-HPV should be used in challenging cases.
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    Efficacy of the Sonoelastography Method for Diagnosis of Fibrosis in Renal Transplant Patients
    (2022) Soudmand, Arash; Ozturk, Funda Ulu; Uslu, Nihal; Haberal, Nihan; Boyvat, Fatih; Moray, Gokhan; Haberal, Mehmet; https://orcid.org/0000-0002-3462-7632; 29993356; AAJ-8097-2021
    Objectives: Although biopsy is the most important method for diagnosing the cause of renal allograft dysfunction, sonoelastography, a new ultrasonography method, can be used to distinguish between the soft or hard nature of lesions. In this study, our aim was to investigate whether sonoelastography could diagnose fibrosis in renal transplant patients. Materials and Methods: In this prospective study, we included patients over 18 years old who were recommended for clinical biopsy. Sonoelastographic evaluation was made by conducting acoustic radiation force impulse measurements for each patient after they were admitted to the clinic for biopsy. Measurements were performed just before the biopsy procedure. All results were examined by 2 experienced radiologists using the Siemens S3000 Ultrasound Machine (Erlangen, Germany). Comparisons of ultrasonographic values with biopsy results were made with SPSS software (SPSS: An IBM Company, version 20, IBM Corporation, Armonk, NY, USA). Results: Of the 65 patients included in this study, pathology showed acute T-cell-mediated rejection in 37 patients. There was a significant correlation between the pathologic Banff scores and the sonographic acoustic radiation force impulse values (P = .002), where the degree of Banff increased as the mean acoustic radiation force impulse values elevated. A rise in mean impulse values correlated with increased degree of interstitial fibrosis in renal allografts. Renal parenchymal echogenicity of patients significantly differed by sex (P = .009), with an average renal echogenicity of grade 1 in women and grade 0 in men. Also, a statistically significant difference was found between age of the renal transplant recipient and resistive index values. Conclusions: Our study showed a significant correlation between Banff degree and the acoustic radiation force impulse values of renal transplant patients. In addition to biopsy, sonoelastography can be beneficial for the diagnosis of fibrosis in renal transplant patients.
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    Antiproliferative and Mitochondrial Protective Effects of Apigenin in an Oxygen-Induced Retinopathy In Vivo Mouse Model
    (2021) Sezenoz, Almila Sarigul; Akkoyun, Imren; Helvacioglu, Fatma; Haberal, Nihan; Dagdeviren, Attila; Bacanli, Didem; Yilmaz, Gursel; Oto, Sibel; 0000-0002-2860-7424; 34665015; AAK-7713-2021
    Purpose: To investigate the effects of a common dietary flavonoid apigenin on retinal endothelial cell proliferation, retinal morphological structure, and apoptotic cell death in an oxygen-induced retinopathy (OIR) mouse model to evaluate the possibility of the use of apigenin in the treatment of ocular neovascular diseases (ONDs). Methods: Ninety-six newborn C57BL/6J mice were included. Eight groups were randomized, each including 12 mice. Two negative control groups were kept in room air: the first without any injection and the second received intravitreal (IV) dimethyl sulfoxide (DMSO), which is the solvent we used. The OIR groups were exposed to 75% +/- 2% oxygen from postnatal days (PD) 7 to 12. On PD 12, the mice were randomly assigned to 6 groups: 2 OIR control groups (1 received no injection, 1 received IV-DMSO), 2 IV-apigenin groups (10 and 20 mu g/mL), and 2 intraperitoneal (IP)-apigenin groups (10 and 20 mg/kg). We quantified retinal endothelial cell proliferation by counting neovascular tufts in cross-sections and examined histological and ultrastructural changes through light and electron microscopy. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). Results: We detected a significant increase in endothelial cell proliferation in the OIR groups. Groups receiving apigenin, both IP and IV, had significant decreases in endothelial cells, atypical mitochondrion count, and apoptotic cells compared with the groups receiving no injections. None of the apigenin-injected groups revealed cystic degeneration or cell loss. Conclusions: Apigenin suppresses neovascularization, has antiapoptotic and antioxidative effects in an OIR mouse model, and can be considered a promising agent for treating OND. Clinical trial (Project number: DA15/19).
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    The Effects Of Tacrolimus And Mycophenolate Mofetil On Regression Of Encapsulating Peritoneal Sclerosis İn A Rat Model
    (2021) Haberal, Nihan
    Objective: Encapsulating peritoneal sclerosis (EPS) is a rare, but potentially fatal complication of peritoneal dialysis. Currently, treatment of peritoneal fibrosis is not fully possible yet. In this study, we aimed to demonstrate the effects of tacrolimus therapy on peritoneal fibrosis and inflammation when administered alone or with mycophenolate mofetil (MMF) in the EPS model induced in rats. Methods: Thirty six Wistar albino rats were separated into six equal groups. Group I was the control group. Group II-VI were administered intraperitoneal chlorhexidine (CH) for induced EPS model in rats. Group II, IV, V, VI were administered isotonic liquid, tacrolimus, tacrolimus and concurrently with CH, tacrolimus and MMF together, respectively. Group III was not administered any drug. All peritoneal samples were stained immunohistochemically with matrix metalloproteinase-2 (MMP-2) antibody. Thickness of peritoneal fibrosis, subserosal large collagen fibers, subserosal fibroblast proliferation and subserosal fibrotic matrix deposition were evaluated. Results: Comparing the experimentally induced EPS groups, the best histopathological results and the largest staining with MMP-2 were achieved in Group VI. Furthermore, in all treatment groups (IV, V, VI) more staining with MMP-2 was detected compared to non-treatment groups (I, II, III) but no statistically significant differences were found among all groups. A statistically significant remission was observed in all histopathological parameters, primarily peritoneal thickness in rats that were administered MMF with tacrolimus, compared to rats which were administered tacrolimus only. Conclusion: Concurrent use of tacrolimus and MMF in the treatment of EPS may be a promising approach.
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    The prognostic significance of stage I ovarian clear cell and endometrioid carcinomas arising from endometriotic cysts: is it a myth?
    (2019) Ayhan, Ali; Akilli, Huseyin; Haberal, Nihan; 30315413
    PurposeThe aim of this study was to determine the clinicopathologic features and the prognostic significance of Stage I ovarian clear cell and endometrioid carcinomas arising from endometriotic cysts.Materials and methodsPatients with either Stage I ovarian clear cell or endometrioid carcinoma were divided into three groups. *Group 1: Patients with cancers arising from endometriotic cysts *Group 2: Patients with ovarian and pelvic endometriosis *Group 3: Patients without endometriosis Patient characteristics (overall survival and disease-free survival) were compared between groups.ResultsOf the 78 patients who participated in this study, 39 were in group 1, 13 were in group 2, and 26 were in group 3. The mean age in groups 1, 2, and 3 were 46years, 54years, and 48years, respectively (p=0.39). Tumoral characteristics, including capsule rupture, positive cytology, grade, and the presence of synchronous endometrial cancer were similar in both groups. The 5-year overall survival rate in groups 1, 2, and 3 were 100, 90, and 93%, respectively (p=0.4). Moreover, the recurrence rates did not differ significantly between groups. Furthermore, subgroup analysis of clear cell carcinoma and endometrioid adenocarcinoma separately showed no effect of endometriosis on disease-free survival (DFS) or overall survival (OS).ConclusionClear cell or endometrioid ovarian carcinoma arising from ovarian and/or pelvic endometriosis shares the same clinicopathologic characteristics with their counterparts that do not arise from endometriosis and patients have similar overall and disease-free survival.
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    Antiproliferative and anti-apoptotic effect of astaxanthin in an oxygen-induced retinopathy mouse model
    (2019) Kucukoduk, Ali; Helvacıoglu, Fatma; Haberal, Nihan; Dagdeviren, Atilla; Bacanli, Didem; Yilmaz, Gursel; Akkoyun, Imren; 0000-0001-8990-8282; 30851776; P-2877-2014
    Objective: To evaluate the impact of intravitreal (IV) and intraperitoneal (IP) astaxanthin (AST) injections on neovascular development (ND), retinal morphology, and apoptotic activity in a C57BL/6J mouse model with hyperoxia-induced retinopathy (HIR). Design: C57BL/6J mouse model. Methods: Two negative control groups (n = 6 each; one of which received IV sterile dimethyl sulfoxide [DMSO]) of C57BL/6J-type mice were exposed to room air. The HIR groups included 36 C57BL/6J-type mice exposed to 75% +/- 2% oxygen from postnatal day (PD) 7 to PD 12. On PD 12, these mice were randomized into 6 groups (n = 6 each): 2 HIR control groups (one of which received IV-DMSO), 2 IV-AST groups (10 and 100 mu g/mL), and 2 IP-AST groups (0.5 and 5 mg/kg). We measured ND by counting neovascular tufts in cross sections and examined histological, ultrastructural changes via light and electron microscopy. Apoptosis was detected using terminal deoxynucleotidyl transferase-mediated nick end-labeling. Results: No ND was detected in the negative control groups. ND levels were not significantly different between high- and low-dose AST for either means of administration. However, ND levels were significantly lower in the AST groups, regardless of delivery, compared to the control groups. The means of delivery (IP versus IV) also yielded significant differences in ND. The incidence of mitochondrial dysmorphology and apoptosis were lower in groups receiving AST. Conclusions: AST seems to suppress ND and has anti-apoptotic activity in the HIR mouse model.
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    Effect of intravitreal and intraperitoneal cyanidin-3-glucoside injection in oxygen-induced retinopathy mouse model
    (2019) Ercan, Zeynep E.; Haberal, Nihan; Helvacioglu, Fatma; Dagdeviren, Atilla; Yİlmaz, Gursel; 0000-0002-9915-3781; 31124490; AAQ-3136-2020
    Purpose: To evaluate the effect of cyanidin-3-glucoside (C3G) in oxygen-induced retinopathy (OIR) mouse model. Methods: In this experimental study, 10 C57BL / 6J type mice exposed to room air comprised two control groups (n = 5 each; a negative control and a group receiving intravitreal sterile dimethyl sulfoxide [IVS DMSO]). Thirty C57BL / 6J type mice exposed to 75% +/- 2% oxygen from postnatal day 7 to postnatal day 12 comprised the OIR groups. On postnatal day 12, these mice were randomized into six groups (n = 5 each): two OIR control groups (negative control and IVS DMSO), two intravitreal C3G groups (300 and 600 ng/mu L), and two intraperitoneal C3G groups (0.05 and 0.1 mg/kg). We quantified neovascularization by counting endothelial cell proliferation on the vitreal side of the inner limiting membrane of the retina and examined histological and ultrastructural changes via light and electron microscopy and apoptosis by terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling. Results: The intravitreal C3G groups yielded lower endothelial cell counts compared with the intravitreal DMSO group. The intraperitoneal high-dose group had lower cell counts compared with the OIR control groups. Electron microscopy revealed significantly less mitochondrial dysmorphology in intravitreal groups and the high-dose intraperitoneal mice. We noted no difference in apoptotic cell count between the controls, low-dose intravitreal, and both intraperitoneal groups. However, apoptotic cell count was significantly higher in the high-dose intravitreal group. Conclusion: C3G suppresses endothelial cell proliferation in an OIR mouse model, leads to a reduced hyperoxia-induced mitochondrial dysmorphology, but increases apoptotic cell death in high concentrations.
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    SEROUS VERSUS HIGH-GRADE ENDOMETRIOID ENDOMETRIAL CARCINOMA: IMMUNOHISTOCHEMISTRY OF RFP IS NOT USEFUL FOR DIFFERENTIATION
    (2016) Ussakli, Cigdem; Usubutun, Alp; Dicner, Nazmiye; Dolgun, Anil; Bulbul, Dilek; Isikdogan, Zuhal; Haberal, Nihan; Ozen, Ozlem; Tezel, Gaye Guler; 0000-0001-9852-9911; 28155970; AAK-4587-2021
    We evaluated the immunohistochemical expression of ret finger protein (RFP) along with conventional immunohistochemical markers in endometrioid and serous carcinomas of the endometrium. A total of 124 endometrial carcinoma cases (24 grade 1 endometrioid, 60 grade 3 endometrioid, 40 serous) were retrieved from pathology archives. Tissue microarrays were constructed. The expression of RFP, WT1, ER., PR, p53 and p16 was examined immunohistochemically. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, kappa statistic for interobserver reproducibility, Kruskal-Wallis test, Mann-Whitney U test and Fisher's exact tests were performed for statistical analyses. The mean RFP score was 1.54 in grade 1 endometrioid, 4.31 in grade 3 endometrioid, and 6.31 in serous carcinomas (p < 0.001). Overall, RFP scores were higher both in serous and grade 3 endometrioid carcinoma (p > 0.05), and significantly lower in grade 1 endometrioid carcinoma (p < 0.05). p16 and p53 staining patterns were able to differentiate between high-grade endometrioid and serous carcinoma (p < 0.001). ER, PR and WT-1 did not reach statistical significance for subtyping. The kappa values of the general agreement between the observers were 0.737 and 0.727 for endometrioid and serous carcinomas respectively (p < 0.001). Diffuse p53 and p16 staining provides the most sensitive and specific immunomarkers for differentiating high-grade endometrioid and serous carcinomas.
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    What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts
    (2017) Bolat, Filiz; Haberal, Nihan; 0000-0001-9852-9911; 28272675; AAK-4587-2021
    Objective: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. Material and Method: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. Results: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells/Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. Conclusion: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.
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    A single-center experience of post-transplant lymphoproliferative disorder (PTLD) cases after pediatric liver transplantation: Incidence, outcomes, and association with food allergy
    (2018) Haberal, Mehmet; Haberal, Nihan; Baris, Zeren; Ozcay, Figen; Ozbek, Ozlem Yilmaz; Sarialioglu, Faik; 29755021; AAB-4153-2020
    Background/Aims: We evaluated our 16-year single-center experience of pediatric post-transplant lymphoproliferative disorder (PTLD) cases who underwent liver transplantation between 2001 and 2017. Materials and Methods: Of the 236 pediatric patients who underwent liver transplantation between 2001 and 2017, the clinical and laboratory data of eight patients diagnosed with PTLD were reviewed. The pre-transplant Epstein-Barr virus (EBV) status of 172 patients was also recorded. Results: The total incidence of PTLD was 3.4%. The incidence of PTLD was 10% in pre-transplant EBV immunoglobulin G (IgG)-seronegative patients and 0.8% in pre-transplant EBV IgG-seropositive patients. The mean age of the patients at liver transplantation was 2.71 +/- 3.21 years, and four patients were aged below 1 year at the time of transplantation. PTLD was diagnosed at 21.81 +/- 18.1 months after transplantation. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach and intestine, transplanted graft, bone marrow, and nasopharynx. The eosinophil count varied greatly among patients, with a mean value of 524.62 +/- 679/mm3. Three patients had a food allergy and were administered an elimination diet at the time of PTLD diagnosis. Six patients had PTLD of B-cell origin. One patient died due to neutropenic sepsis during chemotherapy, whereas seven patients were followed up in full remission for 7.75 +/- 4 years. Conclusion: PTLD is a life-threatening complication of solid-organ transplantation with a heterogeneous clinical spectrum. Food allergy had a close association with PTLD. A close follow-up of patients with risk factors and an early diagnosis with appropriate treatment may lead to a better outcome.