Umran Kucukgoz Gulec

Prognostic Significance of Immune Checkpoint Markers in Prognosis of Grade 3 Endometrioid Carcinoma

Background and Objectives: Uterine FIGO grade 3 endometrioid carcinoma (EC) is an uncommon but aggressive subtype of endometrial cancer with limited biomarker data to guide prognosis and management. This study aimed to evaluate the prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in tumor tissue (TT) and tumor microenvironment (TME). Materials and Methods: We retrospectively analyzed tumor samples from 53 patients with FIGO grade 3 EC. Immunohistochemistry was performed to assess PD-1 and PD-L1 expression in TT and TME. Clinicopathological data including age, stage, lymph node invasion (LNI), lymphovascular space invasion (LVSI), depth of myometrial invasion (MI), adjuvant therapy, and survival outcomes were collected. Survival analyses were conducted using Kaplan–Meier and Cox proportional hazards models. Results: PD-1 expression was identified in 34% of TT and 41.5% of TME, while PD-L1 was expressed in 22.6% of TT and 34% of TME. Except for PD-1 in TME, positive expression of these immune checkpoint molecules correlated with significantly shorter survival (log-rank p < 0.05) outcomes. In univariate analysis, PD-1 and PD-L1 expression in TT, deep MI, LNI and LVSI were associated with adverse outcomes. Multivariate analysis confirmed PD-1 and PD-L1 positivity in TT as independent prognostic factors (PD-1: HR 3.2, 95% CI 1.4–7.0; PD-L1: HR 3.3, 95% CI 1.4–7.8). Patients with concurrent PD-1 and PD-L1 expression in TT showed the poorest overall survival, suggesting a cumulative negative effect. Conclusions: PD-1 and PD-L1 expression in tumor tissue are independent predictors of poor prognosis in FIGO grade 3 EC. These findings support their role as clinically relevant biomarkers and potential therapeutic targets. Incorporating checkpoint evaluation into routine pathological assessment could improve prognostic accuracy and guide treatment strategies, particularly in high-risk patients who might benefit from immunotherapy approaches.

The Cukurova score in the prediction of primary cytoreduction in ovarian cancer

Primary debulking surgery has been the preferred surgical route and is still considered a quality indicator for advanced ovarian cancer surgery. However, a significant number of patients are not amenable to upfront surgery. Neoadjuvant chemotherapy and interval debulking surgery may be the most suitable approach for this group. This study aimed to evaluate a novel score for prediction of the cytoreduction results at primary debulking surgery for ovarian cancer patients. This observational prospective study was conducted at a tertiary gynecologic oncology center between December 2020 and August 2022. Presumed primary stage III-IV epithelial ovarian carcinoma cases were included. Borderline tumors, and metastatic or non-epithelial ovarian malignancies, were excluded. Based on imaging findings, points were assigned to each anticipated surgical procedure required for complete cytoreduction. The sum of these points was multiplied by the patient's Eastern Cooperative Oncology Group (ECOG) score, and thus, the Cukurova-clinic score was established. Furthermore, the required surgical procedures based on laparoscopic evaluation were recorded, and the score was readjusted and calculated to obtain the Cukurova score. One hundred and fourteen patients were included in the study. Primary debulking surgery was performed in 70% of cases. Among them, complete cytoreduction (Cukurova score ≤12) was obtained in 97.3% of cases. Complete cytoreduction was not achieved in cases with Cukurova score >12. The odds ratio of 90-day mortality was 13.4 for patients with Cukurova score >12, compared with those with Cukurova score ≤12. The Cukurova score is a model for classifying advanced ovarian cancer patients who may be candidates for primary debulking surgery.

Prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer

Non-endometrioid endometrial cancers (non-EEC) have different management from endometrioid endometrial cancers. The purpose of this study was to investigate the prognostic significance of omental disease and the role of omentectomy in non-endometrioid endometrial cancer and discuss the current literature with the findings. The study included two hundred-three patients with non-EEC who underwent surgical treatment and follow-up between January 1996 and December 2018 in a University Hospital Gynecologic Oncology Center. The patients were divided into three groups according to whether omentectomy was performed and the presence of omental metastasis. The patient's demographics, clinical characteristics such as stage, grade, histopathologic type, lymphovascular space invasion (LVSI), myometrial invasion, lymph node involvement, and survival outcomes were compared between the groups. The study included 203 patients. Twenty-five patients (12%) had omental metastases. LVSI was reported in 57.3%, 88.0%, and 43.2% of the non-omentectomy, no-omental metastasis, and omental metastatic groups, respectively (p = 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) rates according to the tumor grade, peritoneal cytology, and lymphadenectomy were also compared and were found to be statistically similar. The five-year OS rates were 70.6% for the group without omental metastases and 16.2% for the group with omental metastases, respectively (p = 0.001). In the group of omentectomy, the five-year DFS rates were 62.2% in cases without omental metastasis and 13.0% in cases with omental metastasis (p = 0.001). The five-year OS rates of 86.3% and DFS rates of 80.0% in the group without omentectomy. In non-endometrioid tumors, the survival rate was better in the group that did not undergo omentectomy. Based on these results, we can say that omentectomy may not be necessary for non-endometrioid tumors whose omentum is found to be normal in intraoperative visual examination.

Predictability of lymph node involvement in uterus-confined endometrioid endometrial cancer by tumour size, pattern and location measured with transvaginal ultrasonography: can we save time?

We aimed to investigate whether transvaginal ultrasonography (TVUSG)-measured tumour size, pattern and location were significant predictors for lymph node metastasis in the uterus-confined endometrioid endometrial cancer (EEC) patients. A total of 213 patients with EEC were recruited and 73 of them were considered eligible and were analysed according to lymph node involvement. Tumour size, pattern and location measured by transvaginal ultrasound were recorded. Thereafter, patients were distributed according to their lymph node involvement and were compared with respect to these parameters. The patients' median age was 56 (27-80). Mean of the resected lymph nodes was 29.68 and 33.5 in lymph-node-negative and positive patients, respectively (

Clinicopathologic characteristics and prognosis comparison of the uterine high grade endometrial carcinomas

Grade 3 endometrioid adenocarcinomas (G3 EAC), type two endometrial carcinomas (Type 2 EC), and also uterine carcinosarcomas (UCS) are considered as high-grade endometrial adenocarcinomas. The aim of this study was to compare the clinicopathologic features and survival of patients with UCS, G3 EAC, Type2 EC. We included two hundred and thirty-five patients in this study. Patients were divided into three groups according to the type of tumor as uterine G3 EAC (group 1, n = 62), Type 2 EC (serous, clear and mixed types; group 2, n = 93), and UCS (group 3, n = 80). We compared the groups according to age, initial symptom, surgical approach, stage, myometrial invasion (MI), lymph node invasion (LNI), lymphovascular space invasion (LVSI), adjuvant therapy, and survival. When comparing the survival outcomes the Kaplan-Meier analysis was performed. The groups were similar according to age, menopausal status, nulliparity, initial symptoms, stage, LVSI, and LNI. Positive cytology was determined significantly more in group 3. There was a significant difference between the groups in terms of myometrial invasion degree. Optimal cytoreduction was similar among the groups. The primary adjuvant treatment was chemotherapy for UCS and Type2 EAC whereas radiotherapy was the main adjuvant treatment for G3 EAC. There were no significant differences among the groups according to overall survival (OS) (p = 0.290). Although the survival difference among the groups can not be revealed, these patients have different clinical and pathological features and they should be considered as different groups.

Challenges on the morbidly obese endometrial cancer surgery: Laparotomy or laparoscopy, lymphadenectomy or no lymphadenectomy?

A considerable proportion of endometrial cancer patients are morbidly obese. Management of these cases is a serious dilemma. The aim of this study was to investigate the relevance of laparoscopic route and omission of lymphadenectomy as morbidity-reducing strategies in this special population. Endometrial cancer patients' archival records were retrospectively reviewed and cases with body mass index ≥ 40 kg/m2 were selected. A comparative evaluation of their characteristics and survival rates were performed. Firstly, according to the surgical approach; laparoscopy or laparotomy, and then regarding to performing lymphadenectomy or not. There were 146 patients enrolled in this study. Whereas, significantly higher postoperative complications and longer hospital stays were determined in the laparotomy compared to laparoscopy groups. Five years disease-free and overall survival were not significantly different (83.6% vs 70.7%, p = 0.184 and 83.9% vs 86.6%, p = 0.571, respectively). On the other hand, operation length, postoperative hospitalization time, both intraoperative and postoperative complications were significantly lower in the non-lymphadenectomy compared to the lymphadenectomy groups. However, five-years disease-free and overall survival were not significantly different (77.3% vs 81.3%, p = 0.586 and 87.5% vs 78%, p = 0.479, respectively). Laparoscopic approach and omission of lymphadenectomy are worthy policies in the morbidly obese endometrial cancer patients.

Prognosis Trend of Grade 2 Endometrioid Endometrial Carcinoma: Toward Grade 1 or 3?

Although the prognostic significance of grade in endometrial cancer is well known, grade 2 cases have not been evaluated separately in most of the previous studies. In this study, we aim to investigate whether the oncologic outcomes of grade 2 endometrioid endometrial carcinomas trend towards grade 1 or 3 tumors. Patients' records and pathological reports were reviewed retrospectively and eligible patients with endometrioid endometrial carcinoma were determined and distributed into 3 groups according to their 1988 International Federation of Gynecology and Obstetrics (FIGO) grade. Groups' characteristics and oncologic outcomes were compared. Differences between grades were tested with z-test and adjusted by Bonferroni method. Kaplan-Meier method was performed for the survival analysis. In total, 776 patients of endometrioid endometrial carcinoma were included in this study. Mean follow-up time was 52 ± 14 months. Patients' mean age was 56.3 ± 10.8 years. Even though grade 2 endometrioid endometrial carcinomas were different from both grade 1 and 3 in terms of the pathological features, survival analyses demonstrated that their oncologic outcomes trended towards grade 1. The grade was determined as an independent prognostic factor for overall survival (OS). The interobserver reproducibility will be improved among pathologists by combining FIGO grade 1 and 2 endometrioid endometrial carcinomas, while prognosis prediction is not likely to be affected.

Right diaphragmatic peritonectomy in extensive involvement of the coronary area: no touch principle

Cukurova Score Validation Study

Despite significant advancements in imaging technologies, surgical techniques, chemotherapeutic regimens, and treatment strategies in recent years, ovarian cancer continues to remain the most deadly gynecological malignancy. Approximately 90% of ovarian cancers originate from the coelomic epithelium or modified mesothelial cells and are classified as epithelial ovarian cancers. The majority of patients with epithelial ovarian cancer (70-80%) present in advanced stages. The primary treatment for advanced-stage (stage 3-4) disease consists of primary cytoreductive surgery followed by adjuvant chemotherapy. Cytoreductive surgery aims to remove all visible tumor implants regardless of the extent of the disease and achieve no visible residual tumor (complete cytoreduction, R0) at the end of the surgery. In cases where R0 cannot be achieved (due to poor general condition and/or extensive tumor that cannot be completely excised surgically), the option of neoadjuvant chemotherapy followed by interval cytoreductive surgery is considered. Primary cytoreductive surgery is still the preferred option and is considered a quality indicator for centers performing advanced-stage ovarian cancer surgeries. Despite advancements in surgery, the decision for interval surgery following primary surgery or neoadjuvant chemotherapy is often based on the surgeon's experience, imaging results, and clinic preferences. Various methods and scores have been published and applied to predict which patients are suitable for primary surgery. The Cukurova score developed in our clinic conceptualizes prioritizing surgical procedures using radiological imaging and diagnostic exploratory laparoscopy to achieve complete cytoreduction in harmony with the patient's clinical and performance status, rather than focusing solely on tumor burden. The score showed high success rates for complete cytoreduction and also was useful in terms of predicting the morbidity and mortality. However, the Cukurova score study was conducted in single center. Validation of scores in centers with different capacities is expected to facilitate their widespread use and acceptance. Therefore, in this study, the investigators plan to conduct a validation study of the score in a total of 20 centers in Turkey, including our center. This study aims to evaluate the validity of the Cukurova score in predicting outcomes of primary cytoreduction in advanced ovarian cancer patients and thus determining the decision for primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery.