Scopus İndeksli Açık & Kapalı Erişimli Yayınlar
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Item 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; 34856570Endocervical 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.Item Diagnostic accuracy of sentinel node biopsy in non-endometrioid, high-grade and/or deep myoinvasive endometrial cancer: A Turkish gynecologic oncology group study (TRSGO-SLN-006)(2022) Altin, Duygu; Taskin, Salih; Ortac, Firat; Tokgozoglu, Nedim; Vatansever, Dogan; Guler, Abdul Hamid; Gungor, Mete; Tasci, Tolga; Bese, Tugan; Turan, Hasan; Kahramanoglu, Ilker; Yalcin, Ibrahim; Celik, Cetin; Demirkiran, Fuat; Kose, Faruk; Arvas, Macit; Ayhan, Ali; Taskiran, Cagatay; 35033380Introduction. This study aimed to evaluate the diagnostic accuracy of the sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. Methods. Two hundred forty-four patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicentric study. After removal of SLNs, all patients underwent pelvic +/- paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, negative predictive value (NPV) and false-negative rate (FNR) were calculated. Results. Surgeries were performed via laparotomy in 132 (54.1%) patients and 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. At least 1 SLN was detected in 222 (91%) patients. Fifty-five (225%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN. Lymphatic metastases were detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 182%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%. Conclusion. SLN algorithm had high diagnostic accuracy in high-risk endometrial cancer. All pelvic metastases were detected by the SLN algorithm and the isolated paraaortic metastasis rate was ignorable. But long-term survival studies are necessary before this approach becomes standard of care. (C) 2022 Elsevier Inc. All rights reserved.Item Clinicopathologic and Prognostic Significance of CD47 Expression and Tumor-associated Macrophages in Endometrial Carcinoma(2022) Sercan, Cigdem; Haberal Reyhan, Asuman N.; Ozen, Ozlem; Ayhan, Ali; 34282107Tumor-associated macrophages (TAMs) influence cancer progression. CD47 is an antiphagocytic molecule aiding tumor resistance against host immune surveillance. The relationship between CD47 expression and TAM-related microenvironment in endometrial carcinoma (EC) is poorly understood. The expression and prognostic significance of CD47 and CD163-labeled TAMs in 165 EC cases was assessed with CD47 and CD163 immunohistochemical studies. CD47 expression was found in 156/165 (94.6%) cases. CD47 expression was significantly higher in nonendometrioid carcinomas. CD47 overexpression was associated with histologic grade. High epithelial and stromal TAMs counts were also associated with high tumoral CD47 expression. High epithelial, stromal, and margin TAMs counts were associated with higher histologic grade and lymphovascular invasion. Epithelial TAMs counts were higher in patients with nonendometrioid carcinomas (P=0.0001) and cases with recurrence (P=0.018). High stromal TAMs counts were associated with deeper myometrial invasion (P=0.017) and the presence of distant metastasis (P=0.024). The counts of margin TAMs was significantly correlated with the depth of myometrial invasion, lymphovascular invasion, FIGO stage, lymph node metastases, distant metastasis, and recurrence (P=0.0001, 0.0001, 0.004, 0.005, 0.014, and 0.04, respectively). CD47 expression was not associated with overall survival (OS) and progression-free survival. However, high epithelial and stromal TAM counts were associated with shorter OS. Besides, high epithelial and margin TAM counts were associated with shorter progression-free survival. Furthermore, increased stromal and margin TAM counts were determined to be an independent prognostic marker of reduced OS. TAM count is, therefore, a significant prognostic factor in EC and the CD47 assessment has potential benefit for future clinical use.Item Post-Recurrence Survival In Patients With Cervical Cancer(2022) Cibula, David; Dostalek, Lukas; Jarkovsky, Jiri; Mom, Constantijne H.; Lopez, Aldo; Falconer, Henrik; Scambia, Giovanni; Ayhan, Ali; Kim, Sarah H.; Isla Ortiz, David; Klat, Jaroslav; Obermair, Andreas; Di Martino, Giampaolo; Klat, Jaroslav; Obermair, Andreas; Di Martino, Giampaolo; Pareja, Rene; Manchanda, Ranjit; Kos'un, Jan; dos Reis, Ricardo; Meydanli, Mehmet Mutlu; Odetto, Diego; Laky, Rene; Zapardiel, Ignacio; Weinberger, Vit; Benesova, Klara; Borcinova, Martina; Cardenas, Fernando; Wallin, Emelie; Borcinova, Martina; Cardenas, Fernando; Wallin, Emelie; Anchora, Luigi Pedone; Akilli, Huseyin; Abu-Rustum, Nadeem R.; Barquet-Munoz, Salim Abraham; Javurkova, Veronika; Fischerova, Daniela; van Lonkhuijzen, Luc R. C. W.; https://orcid.org/0000-0002-5240-8441; 34955236; AAX-3230-2020Background. Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Methods. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. Results. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. Conclusions. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.Item The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes(2023) Atilgan, Alev Ok; Akcay, Eda Yilmaz; Ozen, Ozlem; Haberal Reyhan, A. Nihan; Ayhan, Ali; 35466759Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p < 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.Item OPEC Study: An International Multicenter Study Of Ovarian Preservation In Endometrial Cancers(2022) Akgor, Utku; Ayhan, Ali; Shushkevich, Alexander; Ozdal, Bulent; Angelou, Kyveli; Akbayir, Ozgur; Kaidarova, Dilyara; Ulrikh, Elena; Stepanyan, Artem; Ortac, Firat; Aliyev, Shamistan; Ozgul, Nejat; Taranenka, Siarhei; Haberal, Ali; Salman, Coskun; Seyhan, Alper; Selcuk, Ilker; Haidopoulos, Dimitrios; Akilli, Huseyin; Bolatbekova, Raikhan; Alaverdyan, Areg; Taskin, Salih; Murshudova, Sabina; Batur, Meltem; Berlev, Igor; Gultekin, Murat; https://orcid.org/0000-0002-5240-8441; 35323994; AAX-3230-2020Objective To evaluate the feasibility and oncological safety of ovarian preservation in early stage endometrial adenocarcinoma (EC) patients aged 40 and below. Methods A total of 11 institutions from eight countries participated in the study. 169 of 5898 patients aged <= 40 years were eligible for the study. Patients with EC treated between March 2007 and January 2019 were retrospectively assessed. Results The median duration of follow-up after EC diagnosis was 59 months (4-187). Among 169 participants, ovarian preservation surgery (OPS) was performed in 54 (31.9%), and BSO was performed in 115 (68.1%) patients. Although patients younger than 30 years of age were more likely to have OPS than patients aged 30 to 40 years (20.4% vs. 9.6%, P = 0.021), there was no significant difference by the mean age. There were no other relevant baseline differences between OPS and BSO groups. The Kaplan-Meier analysis revealed no difference in either the overall survival (P = 0.955) or recurrence-free survival (P = 0.068) among patients who underwent OPS, and BSO. Conclusion OPS appears to be safe without having any adverse impact on survival in women aged <= 40 years with FIGO Stage I EC.Item Survival In Recurrent Ovarian Cancer Patients Before And After The Bevacizumab Era: An Observational Single-Centre Study(2022) Akilli, Huseyin; Rahatli, Samed; Aliyeva, Khayala; Altundag, Ozden; Kuscu, Ulku Esra; Ayhan, Ali; https://orcid.org/0000-0002-5240-8441; https://orcid.org/0000-0003-0197-6622; 35260031; AAX-3230-2020; W-9219-2019A retrospective observational study was carried out in Baskent University School of Medicine, Ankara, Turkey. Recurrent ovarian cancer patients treated between 2007 and 2017 were divided into two groups according to their bevacizumab status. The primary endpoints were overall survival (OS) and safety. Three hundred and ninety-six patients enrolled in this study, 200 (50.5%) received bevacizumab while 196 (49.5%) patients never received bevacizumab. The median follow-up time was 48.2 and 47.6 months, respectively. The 5-year OS was 61% and 46%, respectively (p=.007). In multivariate analysis, only platinum-sensitivity (HR: 3.75, 95% CI: 3.0-5.32; p<.001) was identified as independent prognostic factors. In subgroup analyses according to platinum status, bevacizumab did not affect the 5 year OS in platinum sensitive patients (64% versus 68% p=.28) but increased survival in platinum resistant patients (36% versus 44%, p=.00). The rate of grade III-IV haematologic toxicities was 13.7% in the bevacizumab group and 11% in the other group (p=.6).Impact Statement What is already known on this subject? Bevacizumab increases the progression-free survival in platinum-sensitive and resistant recurrent ovarian cancer patients without changing overall survival. What do the results of this study add? Bevacizumab did not affect OS in platinum sensitive recurrent ovarian cancer patients however improved OS in platinum resistant patients with mild toxicity. What are the implications of these findings for clinical practice and/or further research? This study emphasised the crucial role of bevacizumab in the treatment of recurrent ovarian cancer patients.Item Incidence of unexpected leiomyosarcoma in a Turkish province: a retrospective multi-centre study in a low income setting(2022) Tasdemir, Umit; Ceran, Mehmet Ufuk; Dirican, Aylin Onder; Akar, Serra; Celik, Cetin; Energin, Hasan; Gorkemli, Huseyin; Mammadova, Narmin; Colak, Eser; Ayhan, Ali; 0000-0003-1923-2373; 0000-0002-8184-7531; 35253591The aim of the current study was to estimate the incidence of unexpected leiomyosarcoma (LMS) in patients who underwent surgery due to leiomyomas in Konya province, and to contribute to the literature discussing comparisons with similar studies. The digital archives of eight high-volume hospitals were studied for surgeries performed due to leiomyomas between January 2012 and January 2019, and leiomyosarcoma incidence was calculated based on the data obtained. Twenty-one patients in 3703 cases were found to have unexpected leiomyosarcoma, which means we can expect one leiomyosarcoma in 176 (0.56%) surgeries. Six more malignant tumours were detected among the remaining cases. Thus, our study estimated the incidence of unexpected leiomyosarcoma as 1/176 (0.56%), which is higher than most of the studies in the literature justifying the debate started by the FDA in 2014. As the tumour biology is not yet clear, and the incidence of unexpected leiomyosarcoma tends to be so high, the key focus must be to try to detect uterine leiomyosarcomas preoperatively for robust patient care.IMPACT STATEMENT What is already known on this subject? The incidence of unexpected leiomyosarcoma varies widely from 1/498 to 1/8300 depending on the study method and the type of procedure, and there is still controversy, even after the FDA statement that led to a major restriction in laparoscopic surgeries due to concerns about inadvertent morcellation of leiomyosarcomas. What do the results of this study add? To the best of our knowledge, the current study found the highest incidence of unexpected leiomyosarcoma, and consequently a serious evaluation of all patients undergoing surgery due to leiomyomas preoperatively considering a leiomyosarcoma candidate is recommended. What are the implications of these findings for clinical practice and/or further research? Studies on tumour biology and novel markers must be supported for accurate preoperative diagnosis of leiomyosarcoma.Item The utility of 1.5 tesla MR-guided adaptive stereotactic body radiotherapy for recurrent ovarian tumor - Case reports and review of the literature(2022) Yavas, Guler; Kuscu, Ulku Esra; Ayhan, Ali; Yavas, Cagdas; Onal, Cem; 36261943Introduction: Although epithelioid ovarian cancer (EOC) is a radiosensitive tumor and radiotherapy (RT) played a significant role in adjuvant treatment management in the past, the role of RT has evolved with the advent of platinum-based chemotherapy regimens. Nonetheless, modern RT techniques may be useful in certain patients particularly those with recurrent disease.Presentation of case: After surgery and chemotherapy, two patients, aged 57 and 70, presented with recurrent lesions in the parailiac region. The recurrent lesions were treated with high field 1.5-Tesla MR-Linac treatment in 5 fractions at a dose of 30 Gy. The patients tolerated the treatment well and were disease free after 12 and 20 months of magnetic resonance guided radiotherapy (MRgRT), respectively.Discussion: MRgRT is a novel and rapidly evolving technology that allows for the highly precise treatment of even mobile targets through direct visualization of the tumor. The majority of patients with EOC frequently present with abdominal-pelvic recurrences. It has been demonstrated that EOC requires high radiation doses for curative treatment. MR-Linac enables monitoring of organ motion during treatment, which is necessary for delivering higher doses to target volumes while sparing surrounding organs.Conclusion: To reduce radiation doses to nearby normal tissues, MRgRT allows for the delivery of hypofractio-nated RT with tight safety margins. Regardless of initial resistance or gradual development of intolerance to standard chemotherapy regimens, the role of RT in patients with persistent or recurrent EOC should be reconsidered.Item Is the extent of lymphadenectomy a prognostic factor in International Federation of Gynecology and Obstetrics stage II endometrioid endometrial cancer?(2021) Cuylan, Zeliha Firat; Akilli, Huseyin; Gungorduk, Kemal; Demirkiran, Fuat; Oz, Murat; Salman, Mehmet Coskun; Sozen, Hamdullah; Celik, Husnu; Gokcu, Mehmet; Bese, Tugan; Meydanli, Mehmet Mutlu; Ozgul, Nejat; Topuz, Samet; Kuscu, Esra; Kuru, Oguzhan; Gokmen, Sibel; Gultekin, Murat; Ayhan, Ali; 33426779Aim This study aimed to evaluate the prognostic significance of adequate lymph node dissection (LND) (>= 10 pelvic lymph nodes (LNs) and >= 5 paraaortic LNs removed) in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II endometrioid endometrial cancer (EEC). Methods A multicenter department database review was performed to identify patients who had been operated and diagnosed with stage II EEC at seven centers in Turkey retrospectively. Demographic, clinicopathological, and survival data were collected and analyzed. Results We identified 284 women with stage II EEC. There were 170 (59.9%) patients in the adequate lymph node dissection (LND) group and 114 (40.1%) in the inadequate LND group. The 5-year overall survival (OS) rate of the inadequate LND group was significantly lower than that of the adequate LND group (84.1% vs. 89.1%, respectively; p = 0.028). In multivariate analysis, presence of lymphovascular space invasion (LVSI) (hazard ratio [HR]: 2.39, 95% confidence interval [CI]: 1.23-4.63; p = 0.009), age >= 60 (HR: 3.30, 95% CI: 1.65-6.57; p = 0.001], and absence of adjuvant therapy (HR: 2.74, 95% CI: 1.40-5.35; p = 0.003) remained as independent risk factors for decreased 5-year disease-free survival (DFS). Inadequate LND (HR: 2.34, 95% CI: 1.18-4.63; p < 0.001), age >= 60 (HR: 2.67, 95% CI: 1.25-5.72; p = 0.011), and absence of adjuvant therapy (HR: 4.95, 95% CI: 2.28-10.73; p < 0.001) were independent prognostic factors for decreased 5-year OS in multivariate analysis. Conclusion Adequate LND and adjuvant therapy were significant for the improvement of outcomes in FIGO stage II EEC patients. Furthermore, LVSI was associated with worse 5-year DFS rate in stage II EEC.