Tıp Fakültesi / Faculty of Medicine

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    Is The Presence of Endometriosis Associated with A Survival Benefit in Pure Ovarian Clear Cell Carcinoma?
    (2018) Sahin, Hanifi; Sari, Mustafa Erkan; Cuylan, Zeliha Firat; Haberal, Asuman Nihan; Sirvan, Levent; Coban, Gonca; Yalcin, Ibrahim; Gungor, Tayfun; Celik, Husnu; Meydanli, Mehmet Mutlu; Ayhan, Ali; https://orcid.org/0000-0001-9852-9911; https://orcid.org/0000-0002-3285-5519; AAJ-5802-2021; 29383437; AAK-4587-2021; AAI-9974-2021; AAL-1923-2021
    The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner. A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups. Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis. Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.
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    Carcinosarcoma of The Ovary Compared to Ovarian High-Grade Serous Carcinoma: Impact of Optimal Cytoreduction and Standard Adjuvant Treatment
    (2018) Yalcin, Ibrahim; Meydanli, Mehmet Mutlu; Turan, Ahmet Taner; Taskin, Salih; Sari, Mustafa Erkan; Gungor, Tayfun; Akbayir, Ozgur; Ayhan, Ali; 29143144; AAJ-5802-2021
    The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner. A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case-control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models. Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0-59, standard error (SE) 15.35] versus 27 months (95% CI 22.6-31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02-5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32-11, p < 0.001] were found to be independent risk factors for decreased OS. DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.
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    Risk Factors for Lymph Node Metastasis among Lymphovascular Space Invasion-Positive Women with Endometrioid Endometrial Cancer Clinically Confined to the Uterus
    (2018) Sari, Mustafa Erkan; Meydanli, Mehmet Mutlu; Yalcin, Ibrahim; Sahin, Hanifi; Coban, Gonca; Celik, Husnu; Kuscu, Esra; Gungor, Tayfun; Ayhan, Ali; 0000-0002-3285-5519; 0000-0002-0992-6980; 30419557; AAD-8494-2019; AAI-9974-2021; AAL-1923-2021; AAI-8792-2021; AAJ-5802-2021
    Introduction: We aimed to assess risk factors for lymph node (LN) metastasis among lymphovascular space invasion(LVSI)-positive women with pure endometrioid endometrial cancer (EC) clinically confined to the uterus. Methods: Medical records of women who underwent primary surgery for EC between 2007 and 2016 at either of 2 gynecological oncology centers were retrospectively reviewed. Patient data were analyzed with respect to LN involvement, and predictive factors for LN metastasis were investigated. Results: 280 patients with surgically staged endometrioid-type EC with LVSI were identified. LN involvement was detected in 88 patients (31.4%) with a systematic LN dissection. In multivariate analysis, elevated baseline serum CA 125 levels, deep myometrial invasion (MMI), adnexal involvement and positive peritoneal cytology were found to be independent risk factors for LN metastasis. In women without deep MMI and elevated baseline serum CA 125 levels, the rate of LN metastasis was 19%. The presence of solely deep MMI increased this probability up to 29.1%. The rate of LN metastasis was found to be 46.8% for women with both deep MMI and elevated baseline serum CA 125 levels. Conclusion: These findings may be useful in the decision- making process for LVSI-positive women who are unstaged. (c) 2018 S. Karger GmbH, Freiburg
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    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-3230-2020
    Background. 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.
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    Risk factors for cervical stromal involvement in endometrioid-type endometrial cancer
    (2021) Toprak, Serhat; Sahin, Eda Adeviye; Sahin, Hanifi; Tohma, Yusuf Aytac; Yilmaz, Ercan; Meydanli, Mehmet Mutlu; https://orcid.org/0000-0001-9418-4733; 33118165; AAE-6482-2021
    ObjectiveThe aim of this study was to identify predictors of cervical stromal involvement in women with endometrioid-type endometrial cancer (EEC). MethodsA total of 795 patients with EEC who underwent comprehensive surgical staging including pelvic and para-aortic lymph node dissection between January 2007 and December 2018 were retrospectively analyzed. Data including age, menopausal status, serum CA-125 levels, tumor size, lymphovascular space invasion (LVSI), depth of myometrial invasion, positive peritoneal cytology, cervical stromal involvement, histologic grade, recurrence, and follow-up duration were recorded. ResultsMedian follow up was 49 months. Cervical stromal invasion was found in 88 patients. Multivariate analysis revealed that presence of LVSI (hazard ratio [HR] 2, 95% confidence interval [CI] 1.02-4.25, P = 0.045), a primary tumor diameter of at least 3 cm (HR 3, 95% CI 1.31-7.25, P = 0.010), and at least 50% deep myometrial invasion (HR 2.7, 95% CI 1.37-5.41, P = 0.004) were independent risk factors for cervical stromal involvement in patients with EEC. ConclusionOur study results suggest that presence of LVSI, a primary tumor diameter of at least 3 cm, and LVSI of at least 50% seem to be independent predictors of cervical involvement in women with EEC. Tumor diameter of >= 3 cm, and lymphovascular space invasion >= 50% seem to be independent predictors of cervical involvement in patients with endometrioid-type endometrial cancer.
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    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; 33426779
    Aim 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.
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    Perioperative SARS-CoV-2 infection among women undergoing major gynecologic cancer surgery in the COVID-19 era: A nationwide, cohort study from Turkey
    (2021) Ayhan, Ali; Oz, Murat; Ozkan, Nazli Topfedaisi; Aslan, Koray; Altintas, Mufide Iclal; Akilli, Huseyin; Demirtas, Erdal; Celik, Osman; Ulgu, Mustafa Mahir; Birinci, Suayip; Meydanli, Mehmet Mutlu; 0000-0002-5240-8441; 33223221; AAJ-5802-2021; AAX-3230-2020
    Objective. The objective of this study was to determine the rate of perioperative SARS-CoV-2 infection among gynecologic cancer patients undergoing major surgery. Methods. The database of the Turkish Ministry of Health was searched in order to identify all consecutive gynecologic cancer patients undergoing major surgery between March 11, 2020 and April 30, 2020 for this retrospective, nationwide, cohort study. The inclusion criteria were strictly founded on a final histopathological diagnosis of a malignant gynecologic tumor. COVID-19 cases were diagnosed by reverse transcriptase polymerase chain reaction testing for SARS-CoV-2. The rate of perioperative SARS-CoV-2 infection and the 30-day mortality rate of COVID-19 patients were investigated. Results. During the study period, 688 women with gynecologic cancer undergoing major surgery were identified nationwide. The median age of the patients was 59 years. Most of the surgeries were open (634/688, 92.2%). There were 410 (59.6%) women with endometrial cancer, 195 (28.3%) with ovarian cancer, 66 (9.6%) with cervical cancer, 14 (2.0%) with vulvar cancer and 3 (0.4%) with uterine sarcoma. The rate of SARS-CoV-2 infections confirmed within 7 days before or 30 days after surgery was 46/688 (6.7%). All but one woman was diagnosed postoperatively (45/46, 97.8%). The rates of intensive care unit admission and invasive mechanical ventilation were 4/46 (8.7%) and 2/46 (4.3%), respectively. The 30-day mortality rate was 0%. Conclusion. In the COVID-19 era, gynecologic cancer surgery may be performed with an acceptable rate of perioperative SARS-CoV-2 infection if the staff and the patients strictly adhere to the established infection control measures. (c) 2020 Elsevier Inc. All rights reserved.
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    Low-grade endometrial stromal sarcoma: A Turkish uterine sarcoma group study analyzing prognostic factors and disease outcomes
    (2021) Ayhan, Ali; Toptas, Tayfun; Oz, Murat; Vardar, Mehmet Ali; Kayikcioglu, Fulya; Ozgul, Nejat; Gokcu, Mehmet; Simsek, Tayup; Tunc, Mehmet; Meydanli, Mehmet Mutlu; 0000-0002-8646-0619; 33375988; AAA-6962-2022
    Objective. To investigate factors associated with refractory disease, recurrence, or death as well as disease-free survival (DFS) and overall survival (OS) in low-grade endometrial sarcoma (LGESS). Methods. A multi-institutional, retrospective study was conducted in a total of 124 patients, who received a curative-intent surgery. The exclusion criteria were as follows: i) history of any other invasive disease; ii) neoadjuvant therapy; iii) fertility sparing surgery; iv) a different diagnosis after review of the slides. Results. All patients underwent hysterectomy, 96% had bilateral salpingo-oophorectomy, and 65% had lymphadenectomy. Twelve (14.8%) of 81 patients undergoing lymphadenectomy had lymph node (LN) metastasis. Of those, 8 (9.8%) had pelvic LN metastasis whereas 4 (5.6% ) had isolated paraaortic LN metastasis. Six of 8 (75%) patients with positive pelvic LNs had concurrent paraaortic LN metastasis. Among 124 patients, 3 patients (2.4%) had refractory disease following primary therapy. During a median follow-up of 45.5 months, 27 (22.3%) of 121 patients who achieved complete remission after primary therapy developed recurrence, and 10 patients (8.1%) died of disease. The 3-year DFS and OS were 76.9% and 93.8%, respectively. Stage was the sole independent prognostic factor in the whole cohort. When analyzing factors within subgroups of stage I and stage >= II, there was no significant prognostic factor for stage I; however, lymphadenectomy and adjuvant chemotherapy were significantly associated with disease outcomes for stage >= II. While lymphadenectomy was related with improved DFS, chemotherapy was associated with poor DFS and OS. Conclusion. The risk of LN metastasis at pelvic as well as paraaortic lymphatic basins is not negligible to omit lymphadenectomy in stage >= II LGESS. Moreover, lymphadenectomy provides significant DFS advantage in patients with extrauterine disease. (C) 2020 Elsevier Inc. All rights reserved.
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    Prognostic Value of the Number of the Metastatic Lymph Nodes in Locally Early-Stage Cervical Cancer: Squamous Cell Carcinoma Versus Non-Squamous Cell Carcinoma
    (2021) Aslan, Koray; Haberal, Ali; Akilli, Huseyin; Meydanli, Mehmet Mutlu; Ayhan, Ali; 0000-0002-5240-8441; 33772630; AAX-3230-2020
    Purpose To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. Methods One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. Results In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs <= 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p < 0.001) and 5-year DFS rates (31.6% vs. 82.2%, respectively; p < 0.001) when compared to those of the SCC group with mLNs <= 2. However, the non-SCC group and the SCC group with mLNs > 2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). Conclusion Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs <= 2.
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    Clinical Outcomes of Patients with High-Grade Ovarian Carcinoma Arising in Endometriosis Compared to Ovarian High-Grade Serous Carcinoma
    (2021) Yalcin, Ibrahim; Sahin, Hanifi; Sari, Mustafa Erkan; Haberal, Asuman Nihan; Sahin, Eda Adeviye; Celik, Husnu; Meydanli, Mehmet Mutlu; Ayhan, Ali; 0000-0003-1185-9227
    Purpose To compare the prognoses of women with high-grade ovarian carcinoma arising in endometriosis (OCAE) to those of women with ovarian high-grade serous carcinoma (HGSC) Material and Methods This multicenter, retrospective, case-control study included patients with OCAE at two gynecologic oncology centers in Turkey between January 2006 and December 2016. Of a total of 202 women with a diagnosis of OCAE, 70 women with high-grade OCAE were included. Each case high-grade OCAE was attributed to two women with ovarian HGSC. Survival analysis was performed using the Kaplan-Meier method. Results Eleven patients with high-grade OCAE had recurrent disease (15.7%) when compared to 47 patients (33.6%) with HGSC (p = 0.008). The 5-year disease-free survival (DFS) rate of the patients having high-grade OCAE was significantly higher than the women with HGSC (78.3% vs. 56.2%; p = 0.007, respectively). According to the 5-year overall survival (OS) rates, there was no significant difference between high-grade OCAE and HGSC (79.5% vs. 70.1%; p = 0.210, respectively). Conclusion Although this retrospective study demonstrated a significant decrease in recurrence rate and an increase in the 5-year DFS rate in patients with high-grade OCAE, OS rates of the patients with HGSC and high-grade OCAE seem to be similar.