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    High-grade endometrial stromal sarcoma versus undifferentiated uterine sarcoma: a Turkish uterine sarcoma group study-001
    (2021) Ayhan, Ali; Tunc, Mehmet; Boran, Nurettin; Khatib, Ghanim; Gokcu, Mehmet; Simsek, Tayup; Ozen, Ozlem Isiksacan; Toptas, Tayfun; Yalcin, Ibrahim; Meydanli, Mehmet Mutlu; https://orcid.org/0000-0002-9082-1317; 33392719; AAK-4468-2021
    Objective Prognostic factors associated with high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS) have not been distinctly determined due to the repetitive changes in the World Health Organization (WHO) classification. We aimed to compare clinicopathologic features and outcomes of patients with HGESS with those of patients with UUS. Methods A multi-institutional, retrospective, cohort study was conducted including 71 patients, who underwent surgery at 13 centers from 2008 to 2017. An experienced gynecopathologist from each institution re-evaluated the slides of their own cases according to the WHO2014 classification. Factors associated with refractory/progressive disease, recurrence or death were examined using logistic regression analyses. Kaplan-Meier method and log-rank test were used for survival comparisons. Results The median disease-free survival (DFS) for HGESS and UUS was 12 months and 6 months, respectively. While the median overall survival was not reached in HGESS group, it was 22 months in the UUS group. Kaplan-Meier analyses revealed that patients with UUS had a significantly poorer DFS than those with HGESS (p = 0.016), although OS did not differ between the groups (p = 0.135). Lymphovascular-space involvement (LVSI) was the sole significant factor associated with progression, recurrence or death for HGESS (Hazard ratio: 9.353, 95% confidence interval: 2.539-34.457, p = 0.001), whereas no significant independent factor was found for UUS. Conclusions UUS has a more aggressive behavior than HGESS. While no significant predictor of prognosis was found for UUS, LVSI is the sole independent prognostic factor for HGESS, with patients 9.3 times more likely to experience refractory/progressive disease, recurrence or death.
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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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    Is the Oncological Outcome of Early Stage Uterine Carcinosarcoma Different from That of Grade 3 Endometrioid Adenocarcinoma?
    (2021) Gungorduk, Kemal; Plett, Helmut; Gulseren, Varol; Meydanli, Mutlu; Boyraz, Gokhan; Ozdemir, Isa Aykut; Sahin, Hanifi; Senol, Taylan; Yildirim, Nuri; Turan, Taner; Oge, Tufan; Gokcu, Mehmet; Taskin, Salih; Ayhan, Ali; Ataseven, Beyhan; 33249415; AAJ-5802-2021
    Aim: The clinicopathologic characteristics, recurrence patterns, and survival of patients with grade 3 endometrial cancer (G3-EAC) and uterine carcinosarcoma (UCS) were compared. Materials and Methods: The medical records of patients treated for G3-EAC and UCS between January 1996 and December 2016 at 11 gynecologic oncology centers in Turkey and Germany were analyzed. Results: Of all patients included in the study, 161 (45.1%) were diagnosed with UCS and 196 (54.9%) with G3-EAC at FIGO stage I-II (early stage) disease. The recurrence rate was higher in patients with UCS than in those with G3-EAC (17.4 vs. 9.2%, p = 0.02). The 5-year disease-free survival (DFS; 75.2 and 80.8%, respectively; p = 0.03) and overall survival (OS; 79.4 and 83.4%, respectively; p = 0.04) rates were significantly lower in the UCS group compared to the G3-EAC group. UCS histology was an independent prognostic factor for decreased 5-year DFS (HR 1.8, 95% CI 1.2-3.2; p = 0.034) and OS (HR 2.7, 95% CI 1.3-6.9; p = 0.041) rates. Conclusions: The recurrence rate was higher in UCS patients than in G3-EAC patients, regardless of disease stage. DFS and OS were of shorter duration in UCS than in G3-EAC patients. Adequate systematic lymphadenectomy and omentectomy were an independent prognostic factor for increased 5-year DFS and OS rates.
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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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    Impact of cytoreductive surgery on survival of patients with low-grade serous ovarian carcinoma: A multicentric study of Turkish Society of Gynecologic Oncology (TRSGO-OvCa-001)
    (2021) Vatansever, Dogan; Taskiran, Cagatay; Mutlu Meydanli, Mehmet; Gungorduk, Kemal; Akbayir, Ozgur; Yalcin, Ibrahim; Demirkiran, Fuat; Sozen, Hamdullah; Ozgul, Nejat; Celik, Husnu; Onan, Mehmet Anil; Taskin, Salih; Oge, Tufan; Simsek, Tayyup; Abboud, Sara; Yuksel, Ilkbal Temel; Ayhan, Ali; 33657253; AAL-1923-2021; AAJ-5802-2021
    Background and Objectives The aim of this study was to analyze the factors affecting recurrence-free (RFS) and overall survival (OS) rates of women diagnosed with low-grade serous ovarian cancer (LGSOC). Methods Databases from 13 participating centers in Turkey were searched retrospectively for women who had been treated for stage I-IV LGSOC between 1997 and 2018. Results Overall 191 eligible women were included. The median age at diagnosis was 49 years (range, 21-84 years). One hundred seventy-five (92%) patients underwent primary cytoreductive surgery. Complete and optimal cytoreduction was achieved in 148 (77.5%) and 33 (17.3%) patients, respectively. The median follow-up period was 44 months (range, 2-208 months). Multivariate analysis showed the presence of endometriosis (p = .012), lymphovascular space invasion (LVSI) (p = .022), any residual disease (p = .023), and the International Federation of Gynecology and Obstetrics (FIGO) stage II-IV disease (p = .045) were negatively correlated with RFS while the only presence of residual disease (p = .002) and FIGO stage II-IV disease (p = .003) significantly decreased OS. Conclusions The maximal surgical effort is warranted for complete cytoreduction as achieving no residual disease is the single most important variable affecting the survival of patients with LGSOC. The prognostic role of LVSI and endometriosis should be evaluated by further studies as both of these parameters significantly affected RFS.
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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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    Factors affecting parametrial involvement in cervical cancer patients with tumor size <= 4 cm and selection of low-risk patient group
    (2021) Akilli, Huseyin; Tohma, Yusuf Aytac; Gunakan, Emre; Kucukyildiz, Irem; Tunc, Mehmet; Haberal, Nihan Reyhan; Ayhan, Ali; 0000-0002-5240-8441; 0000-0001-9418-4733; 0000-0001-8854-8190; 0000-0001-9852-9911; 33506671; AAX-3230-2020; AAE-6482-2021; ABI-1707-2020; AAK-4587-2021
    Objective: The primary aim of this study was to evaluate the factors affecting parametrial involvement in cervical cancer patients with tumor size <= 4 cm and selection of the low-risk patient group based on long-term oncologic outcomes. Material and Methods: Cervical cancer patients operated in the gynecologic oncology division between 2007 and 2013 were retrospectively evaluated. One-hundred and sixty-eight patients with tumor size <= 4 cm were identified. Of these, 159 (86.8%) underwent radical hysterectomy plus pelvic-para- aortic lymphadenectomy and nine (13.2%) underwent fertility-sparing surgery [radical trachelectomy (n= 7); large conization (n=2)]. Factors affecting parametrial invasion, including lymphovascular space invasion (LVSI), deep stromal invasion (DSI), lymph node metastases, and tumor size, were evaluated. Statistical analyses were performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA). Results: Median age was 49.5 years and median tumor size was 2.5 cm ( 0.45-4 cm). In both univariate and multivariate analyses, the risk of parametrial involvement was increased with LVSI with a hazard ratio (HR) of 3.45 [95% confidence interval (CI): 1.1-10.8] and DSI with a HR of 4.1 (95% CI: 1.18-14.8), while tumor size of <= 2 cm was only significant in univariate analyses. Furthermore, 26 early-stage patients were identified with low-risk factors and they had no parametrial involvement, lymph node metastases, recurrence, or death from disease over 77 months. Conclusion: Parametrial involvement in low-risk cervical cancer is very rare and less radical procedures may be safe in these patients.
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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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    Complications of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: An evaluation of 100 cases
    (2021) Akilli, Huseyin; Gunakan, Emre; Haberal, Ali; Altundag, Ozden; Kuscu, Ulku Esra; Taskiran, Cagatay; Ayhan, Ali; 0000-0002-5240-8441; 0000-0001-8854-8190; 0000-0003-0197-6622; 34038007; AAX-3230-2020; ABI-1707-2020; W-9219-2019
    Objective To evaluate the perioperative outcomes and complications of patients with peritoneal carcinomatosis who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). Methods This retrospective study included 100 patients operated on between 2016 and 2020. Patients' characteristics, including age, comorbidities, chemotherapy history, treatment failures, cancer type, histology, platinum sensitivity, and perioperative complications, were documented. Perioperative complications were classified according to the Clavien-Dindo classification. Results Median age was 58 years and median follow-up time was 16 months. Eighty-six (86%) patients had ovarian cancer; 11 (11%) experienced grade III-IV complications, and the only relevant factor was the presence of multiple metastasis (P = 0.031). Seven patients (7%) had surgical-site infection; in multivariant analyses, only ostomy formation was found as an independent risk factor for surgical-site infection (odds ratio [OR] 14.01; 95% confidence interval [CI] 1.36-143.52; P = 0.024). Fifteen (15%) patients experienced elevated serum creatinine after surgery and the median time to creatinine elevation was 5 days postoperatively (range 3-15 days). In multivariant analyses, only age of of 58 years or more was found as a significant factor for the elevation of serum creatinine (OR 6.96; 95% CI 1.42-32.81; P = 0.014). Conclusion Our results showed that the presence of multiple metastases increased the risk of grade III-IV complications and age of 58 years or more was the leading risk factor for renal complications. However, we could not find a relation between postoperative complications and oncologic outcomes. HIPEC seems to be a safe approach in experienced hands.
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    Feasibility of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Ovarian Cancer During COVID-19 Pandemic
    (2021) Ayhan, Ali; Yilmaz Baran, Safak; Vatansever, Dogan; Dogan Durdag, Gulsen; Celik, Husnu; Taskiran, Cagatay; Akilli, Huseyin; 0000-0001-5874-7324; 0000-0002-5240-8441; 33858953; AAX-3230-2020
    Objective This study aims to evaluate the effect of the COVID-19 pandemic and related restrictions on patients who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer. Methods We retrospectively evaluated ovarian cancer patients who underwent HIPEC following complete cytoreductive surgery performed during the outbreak of the COVID-19 pandemic in three different centers specializing in gynecological oncology. All patients who underwent cytoreduction plus HIPEC for a primary, interval, and recurrent surgery were evaluated. Primary outcomes was postoperative 30-day morbidity and mortality. The secondary outcome was infection of patient and/or related staff with COVID-19 during the perioperative or early postoperative period. Results We performed a total of 35 HIPEC procedures during the pandemic: 15 (42.9%) patients underwent primary/interval surgery, while 20 (57.1%) patients had recurrent disease. Grade 3-4 complications occurred in one patient (2.9%) (chronic renal failure), while mortality did not occur in any patient. Neither the patients nor related staff were infected with the coronavirus during the perioperative or early postoperative period. One patient, who was diagnosed with COVID-19 pneumonia on postoperative day 80 died from the infection. Another patient died on postoperative day 85 due to progressive ovarian cancer, a disorder in vital functions, and organ failure. Conclusion HIPEC during the COVID-19 pandemic seems a safe and feasible procedure, with acceptable morbidity and mortality rates. Careful selection of patients is important and precautions should be taken before the procedure.