Tıp Fakültesi / Faculty of Medicine

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    Determination of Risk Factors for Postoperative Acute Kidney Injury in Patients With Gynecologic Malignancies
    (2023) Doganci, Melek; Zeyneloglu, Pinar; Kayhan, Zeynep; Ayhan, Ali; 37575800; IVV-1127-2023; C-3736-2018; AAJ-4623-2021
    BackgroundPostoperative acute kidney injury (AKI) is an important cause of mortality and morbidity among surgical patients. There is little information on the occurrence of AKI after operations for gynecologic malignancies. This study aimed to determine the incidence of AKI in patients who underwent surgery for gynecological malignancies and determine the risk factors in those who developed postoperative AKI. MethodologyA total of 1,000 patients were enrolled retrospectively from January 2007 to March 2013. AKI was defined according to the Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline for Acute Kidney Injury. Perioperative variables of patients were collected from medical charts.ResultsThe incidence of postoperative AKI was 8.8%, with stage 1 occurring in 5.9%, stage 2 in 2.4%, and stage 3 in 0.5% of the patients. Patients who had AKI were significantly older, had higher body mass index (BMI) higher preoperative C-reactive protein (CRP) levels, and more frequently had a history of distant organ metastasis when compared with those who did not have AKI. When compared with patients who did not develop AKI postoperatively, longer operation times and intraoperative usage of higher amounts of erythrocyte suspension and fresh frozen plasma were seen in those who developed AKI. ConclusionsPatients who had AKI were older, had higher BMI with higher preoperative CRP levels, more frequent distant organ metastasis, longer operation times, and higher amounts of blood transfused intraoperatively. Defining preoperative, intraoperative, and postoperative risk factors for postoperative AKI and taking necessary precautions are important for the early detection and intervention of AKI.
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    Oncologic and Obstetric Outcomes of Early-Stage Epithelial Ovarian Cancer Patients Who Underwent Fertility-Sparing Surgery: A Retrospective Study
    (2023) Ayhan, Ali; Tunc, Mehmet; Atasoy Karakas, Latife; Tekelioglu, Tugba; Haberal Reyhan, Asuman Nihan; Onalan, Gogsen; Kuscu, Esra; 0000-0002-8646-0619; 0000-0001-7369-5470; 36825554; AAA-6962-2022; AAI-8793-2021
    ObjectiveThis study aimed to assess the long-term oncologic and obstetric outcomes of women with epithelial ovarian cancer who underwent fertility-sparing surgery. MethodsA total of 68 patients observed between March 2007 and July 2021 were included in this retrospective study. Unilateral salpingo-oophorectomy and uterine preservation with staging surgery were the main procedures for fertility-sparing surgery. Disease-free, overall survival, and obstetric outcomes were measured as primary outcomes. ResultsThe median age of the patients was 30.5 years. The median follow-up time was 60.5 months. Disease recurrence occurred in 15 (22.1%) of the patients. Five-year disease-free survival and overall survival (OS) percentages were 75.6% and 83.3%, respectively, for all stages. The FIGO (International Federation of Gynecology & Obstetrics) stage was the only significant factor that affected OS (P = 0.001). Twenty-three patients tried to conceive, and 15 (65.2%) patients became pregnant. Twelve (80%) pregnancies reached term and resulted in 15 live births. Chemotherapy administration and surgical intervention (cystectomy or unilateral salpingo-oophorectomy) showed no difference in pregnancy results (P = 0.806 and P = 0.066, respectively). ConclusionFertility preservation is safe for invasive epithelial ovarian cancer at early stages for women in the reproductive era. Disease recurrence and OS results are similar to standard treatment at early stages with decent obstetric outcomes.
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    Carrier Screening Programs for Rare Diseases in Developed Countries and the Case of Turkey: A Systematic Review
    (2023) Fidan, Caglar; Akdur, Recep; Unver, Cigdem Naz; Sahin, Omer Can; Alper, Asli Begum; Ayhan, Ali; 37662625
    Effective control of rare diseases requires health programs based on principles of protection and prevention. Carrier screening programs serve as preventive measures by identifying at -risk groups. This review examines the impact, implementation, advantages, and disadvantages of carrier screening, incorporating examples from ten countries: the United States, Canada, the United Kingdom, Israel, China, Australia, Italy, Germany, the Netherlands, and Turkey. Data on carrier screening and related policies were collected from July to November 2022 and presented in a tabular format using a coding system devised by the authors. Variability was observed in the diseases/disorders and populations screened, screening expenses, and government provision across the countries. The number of diseases/disorders examined, ranging from 3 to 47, was determined by committee guidelines, government resources, pilot studies, and national institute resources. Notably, carrier screening programs exhibited greater worldwide inconsistency compared to newborn screening programs. The comparative analysis of developed countries serves to guide emerging nations. To address inequalities at both local and global levels, there is a need to enhance the establishment, development, and implementation of carrier screening programs. Furthermore, cost analyses of screening should be conducted, and adequate funding should be allocated to countries. In conclusion, this review highlights the preventive potential of carrier screening for rare diseases and emphasizes the importance of improving carrier screening programs globally to achieve equitable healthcare outcomes.
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    Evaluation of Colposcopy After the Addition of Human Papillomavirus Testing to the Turkish Cervical Cancer Screening Program
    (2023) Gunes, Ali Can; Ozgul, Nejat; Turkyilmaz, Murat; Kara, Fatih; Unlu, Fahriye; Ayhan, Ali; Gultekin, Murat; 37994572
    Objective: To evaluate colposcopy performance following the human papillomavirus (HPV) DNA screening program in Turkey. Methods: Women aged 30-65 years are screened for cervical cancer every 5 years, with individuals positive for HPV 16 and/or 18 or other high-risk HPV types with abnormal cytology referred for colposcopy. Both HPV test and cytology are obtained at the same visit. If HPV is negative, cytology will not be assessed. However, if HPV is positive, both cytology and HPV genotyping will be performed. Colposcopy-require was defined as HPV 16/18 positivity or abnormal smear results with any hrHPV positivity, and the remaining patients (normal smear with hrHPV positivity other than HPV 16/18) were grouped as colposcopy non-required. National data on colposcopy outcomes and unnecessary performance rates in February 2018-2019 were evaluated via a questionnaire. Results: A total of 9808 patients were included, divided based on colposcopy requirement: 5751 (58.6%) patients required colposcopy and 4057 (41.4%) did not. Unnecessary colposcopy was performed on 90.1% of the non-required group (3657 of 4057 patients). In the colposcopy-required group, 4455 patients (79.9%) underwent punch biopsy; 3194 (57.1%), endocervical curettage (ECC); and 421 (7.5%), "see and treat" in the non-required group, the results were 2790 (76.3%), 1957 (53.2%), and 211 (5.7%), respectively. A total of 746 cervical intraepithelial neoplasia (CIN)-3 isolates were detected, including 702 using existing screening and triage with 94.1% sensitivity (702/746). Multiple biopsies were taken in 69.8% (n = 3110) of patients from the colposcopy-required group and 63.7% (n = 1777) from the non-required group. The ECC samples included 19 cervical cancers and 212 >= CIN-3 lesions in the colposcopy-required group, and four cancers and 41 >= CIN-3 lesions in the non-required group. The proportion of >= CIN-3 lesions detected by ECC only was 4.7% (35 of 746 >= CIN-3 lesions). Conclusion: Our results showed high rates of unnecessary colposcopies, and a high percentage of multiple and random punch biopsies and ECC.
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    Survival Associated with Extent of Radical Hysterectomy in Early-Stage Cervical Cancer: A Subanalysis of the Surveillance in Cervical Cancer (SCCAN) Collaborative Study
    (2023) Bizzarri, Nicolo; Querleu, Denis; Dostalek, Lukas; van Lonkhuijzen, Luc R. C. W.; Giannarelli, Diana; Lopez, Aldo; Salehi, Sahar; Ayhan, Ali; Kim, Sarah H.; Ortiz, David Isla; Klat, Jaroslav; Landoni, Fabio; Pareja, Rene; Manchanda, Ranjit; Kostun, Jan; Ramirez, Pedro T.; Meydanli, Mehmet M.; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Dos Reis, Ricardo; Anchora, Luigi Pedone; Amaro, Karina; Akilli, Huseyin; Abu Rustum, Nadeem R.; Salcedo Hernandez, Rosa A.; Javurkova, Veronika; Mom, Constantijne H.; Scambia, Giovanni; Falconer, Henrik; Cibula, David; 37336255
    BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer.OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence.STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy.RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter <= 20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70).CONCLUSION: For tumors <= 20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve sparing radical hysterectomy after propensity score match analysis.
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    Clinicopathologic Features and the Loss of ARID1A Expression in Ovarian Seromucinous Borderline Tumors and Seromucinous Carcinomas
    (2023) Ok Atilgan, Alev; Ozen, Ozlem; Haberal Reyhan, A. Nihan; Ayhan, Ali; 36452965
    The current study highlighted the ARID1A and SALL4 expression and described histopathologic and immunohistochemical features of ovarian seromucinous tumors (SMTs) including borderline tumors (SMBTs) and seromucinous carcinomas (SMC; namely as endometrioid carcinoma with mucinous differentiation according to WHO 2020 classification). The clinicopathological and immunohistochemical features of 38 SMTs were analyzed, including ARID1A, SALL4, estrogen receptor (ER), progesterone receptor (PR), TP53, keratin 7, keratin 20, CEA, CDX2, WT1, PAX2, and PAX8. SMCs and SMBTs comprised 68.4% (n = 26) and 31.6% (n = 12) of all SMTs, respectively, studied. The mean age of diagnosis was 47.4 years and 41.4 years, and the mean size was 9 cm and 7.45 cm for SMC and SMBT, respectively. There was endometriosis or endometriotic cyst in 61.5% of SMCs and 50% of SMBTs. Immunohistochemically, loss of ARID1A staining was observed in 15 (65.2%) of 26 SMCs, and 3 (33.3%) of the 12 SMBTs. Only one SMC showed focal SALL4 positivity. All SMTs were positive for ER, PR, PAX8, and keratin 7. SMTs were negative for WT1, keratin 20, CDX2, and CEA (negative in 66.7% to 92.3% of the cases). While all SMBTs and 24 (92.3%) of 26 SMCs exhibited "wild-type" TP53 staining, 2 (7.7%) SMCs, both were stage III, showed mutant type TP53 overexpression. We indicate there is a similarity between SMC and SMBT according to the immunohistochemical features. SMBTs are keratin 7, ER, PR positive tumors, and some of them have loss of ARID1A expression and are likely to develop in the background of endometriosis similar to SMC.
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    The Impact of Hospital Surgical Volume on Survival in Early-Stage Cervical Cancer Treated with Radical Hysterectomy: A Sub-Analysis of the Sccan Study
    (2022) Bizzarri, Nicolo; Dostalek, Lukas; Lonkhuijzen, Luc R. C. W.; Giannarelli, Diana; Lopez, Aldo; Falconer, Henrik; Querleu, Denis; Ayhan, Ali; Kim, Sarah H.; Isla Ortiz, David; Klat, Jaroslav; Obermair, Andreas; Landoni, Fabio; Rodriguez, Juliana; Manchanda, Ranjit; Kostun, Jan; Ramirez, Pedro T.; Meydanli, Mehmet M.; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Dos Reis, Ricardo; Anchora, Luigi Pedone; Amaro, Karina; Salehi, Sahar; Akilli, Huseyin; Abu Rustum, Nadeem R.; Salcedo Hernandez, Rosa A.; Javurkova, Veronika; Mom, Constantijne H.; Scambia, Giovanni; Cibula, David; 0000-0002-5240-8441; AAX-3230-2020
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    Role of Adjuvant Therapy in Intermediate-Risk Cervical Cancer Patients - Sccan Study Sub-Analysis
    (2022) Cibula, David; Akilli, Huseyin; van Lonkhuijzen, Luc R. C. W.; Fagotti, Anna; Dostalek, Lukas; Isla Ortiz, David; Meydanli, Mehmet Mutlu; Abu-Rustum, Nadeem R.; Odetto, Diego; Landoni, Fabio; Presl, Jiri; Klat, Jaroslav; Falconer, Henrik; Lopez, Aldo; dos Reis, Ricardo; Zapardiel, Ignacio; Laky, Rene; Mom, Constantijne H.; Bizzarri, Nicolo; Ayhan, Ali; 0000-0002-5240-8441; AAX-3230-2020
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    Deep Cervical Injection: A Novel Technique to Increase Bilateral Sentinel Lymph Node Detection Rate in Endometrial Cancer Patients with Indocyanine Green (Trsgosln-008)
    (2022) Vatansever, Dogan; Altin, Duygu; Giray, Burak; Taskin, Salih; Donmez, Emin; Tokgozoglu, Nedim; Guler, Abdul Hamid; Tasci, Tolga; Bese, Tugan; Turan, Hasan; Kahramanoglu, Ilker; Yalcin, Ibrahim; Celik, Cetin; Demirkiran, Fuat; Gungor, Mete; Ortac, Firat; Kose, Faruk; Arvas, Macit; Ayhan, Ali; Taskiran, Cagatay; 0000-0003-1902-8014; HIR-3028-2022
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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.