Isin Ureyen

Prediction of Clavien Dindo Classification ≥ Grade III Complications After Epithelial Ovarian Cancer Surgery Using Machine Learning Methods

Background and Objectives: Ovarian cancer surgery requires multiple radical resections with a high risk of complications. The aim of this single-centre, retrospective study was to determine the best method for predicting Clavien–Dindo grade ≥ III complications using machine learning techniques. Material and Methods: The study included 179 patients who underwent surgery at the gynaecological oncology department of Antalya Training and Research Hospital between January 2015 and December 2020. The data were randomly split into training set n = 134 (75%) and test set n = 45 (25%). We used 49 predictors to develop the best algorithm. Mean absolute error, root mean squared error, correlation coefficients, Mathew’s correlation coefficient, and F1 score were used to determine the best performing algorithm. Cohens’ kappa value was evaluated to analyse the consistency of the model with real data. The relationship between these predicted values and the actual values were then summarised using a confusion matrix. True positive (TP) rate, False positive (FP) rate, precision, recall, and Area under the curve (AUC) values were evaluated to demonstrate clinical usability and classification skills. Results: 139 patients (77.65%) had no morbidity or grade I-II CDC morbidity, while 40 patients (22.35%) had grade III or higher CDC morbidity. BayesNet was found to be the most effective prediction model. No dominant parameter was observed in the Bayesian net importance matrix plot. The true positive (TP) rate was 76%, false positive (FP) rate was 15.6%, recall rate (sensitivity) was 76.9%, and overall accuracy was 82.2% A receiver operating characteristic (ROC) analysis was performed to estimate CDC grade ≥ III. AUC was 0.863 with a statistical significance of p < 0.001, indicating a high degree of accuracy. Conclusions: The Bayesian network model achieved the highest accuracy compared to all other models in predicting CDC Grade ≥ III complications following epithelial ovarian cancer surgery.

Neoadjuvant chemotherapy in patients with stage IVB uterine serous carcinoma: a Turkish multicentric study

The aim of this study was to evaluate the prognostic factors for and determine the effect of neoadjuvant chemotherapy (NACT) on oncologic outcome in stage IVB pure serous endometrial carcinoma patients who received taxane and platinum. Forty-two patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IVB uterine serous carcinoma were enrolled from six gynecologic oncology centers and a study group was created. The study group had a 2-year disease-free survival (DFS) of 32% and 2-year disease-specific survival (DSS) of 73%. On univariate analysis; lymphadenectomy (not performed vs. performed), paraaortic lymph node metastasis (positive vs. negative) and number of metastatic lymph node count (≤5 vs. >5) were found to have statistical significance for DFS (

Factors predicting recurrence in patients with stage IA endometrioid endometrial cancer: what is the importance of LVSI?

The aim of this study is to define the clinical and pathological prognostic factors for recurrence and to evaluate the recurrence patterns and adjuvant therapies used in this group of patients with stage IA endometrioid type endometrial cancer (FIGO 2009-International Federation of Gynecology and Obstetrics). Among the patients with epithelial endometrial cancer operated between January 1993 and May 2013 in a single institution, 720 patients with stage IA endometrioid endometrial cancer were included. Patients with a tumor type of serous, clear cell, mucinous, undifferentiated, and mixed type and with a tumor containing sarcomatous component and the patients with a secondary primer cancer were excluded from the study. Lympho-vascular space invasion (LVSI) was present in 60 (8.3%) patients. Pelvic and para-aortic lymphadenectomy was performed in 266 (36.9%) patients. Median follow-up time was 48 months (range 3-240). Recurrence occurred in 23 (3.4%) patients and 6 (0.9%) died of disease. The median time-to recurrence (TTR) was 24 months (range 4-52 months) in the patients with recurrence. LVSI was associated with recurrence in the univariate analysis. Five-year disease-free survival (DFS) decreased from 96.8 to 80.1% in the presence of LVSI (p < 0.001). This association could not be shown in patients who had had lymphadenectomy (p = 0.136). Extra-pelvic recurrence occurred in 6.7% and 1% of the patients with and without LVSI, respectively, (p = 0.001). Any independent prognostic factor could not be detected in the multivariate analysis. Only LVSI and tumor grade were associated with DFS and disease-specific survival (DSS), respectively, in the 686 patients with stage IA endometrial cancer in the univariate analysis, since these associations could not be shown in multivariate analysis.

Assessment of the differences in oncologic outcomes between patients with high‐grade serous ovarian carcinoma and uterine serous carcinoma

AbstractAimTo evaluate whether the recurrence rates, recurrence patterns, and survival outcomes differed according to the primary site of the tumor in patients with high‐grade serous ovarian carcinoma (HGSOC) and uterine serous carcinoma (USC).MethodsThe population of this multicenter retrospective study consisted of patients who had USC or HGSOC. Progression‐free survival (PFS) and disease‐specific survival (DSS) estimates were determined using the Kaplan–Meier method. Survival curves were compared using the log‐rank test.ResultsThe study cohort consisted of 247 patients with HGSOC and 34 with USC. Recurrence developed in 118 (51.1%) in the HGSOC group and 14 (42.4%) in the USC group (p = 0.352). The median time to recurrence was 23.5 (range, 4–144) and 17 (range, 4–43) months in the HGSOC and USC groups, respectively (p = 0.055). The 3‐year PFS was 52% in the HGSOC group and 47% in the USC group (p = 0.450). Additionally, 3‐year DSS was 92% and 82% in the HGSOC and USC groups, respectively (p = 0.060).ConclusionsHGSOC and USC are aggressive tumors with high recurrence and mortality rates in advanced stages. These two carcinomas, which are similar in molecular features and clinical management, may also have similar recurrence patterns, disease failure, and survival rates.

Nicotinamide Phosphoribosyltransferase (NAMPT) as a New Marker in Cervical Preinvasive Lesions

Objective To examine the relationship between cervical dysplasia and tissue levels of nicotinamide phosphoribosyltransferase (NAMPT). Materials and Methods Patients who underwent colposcopic biopsy due to human papilloma virus positivity were classified as normal tissue and cervical intraepithelial neoplasia (CIN) 1, CIN 2-3. These were stained with NAMPT antibodies using streptavidin-biotin peroxidase method (Invitrogen, 85-9043, CA, USA). The staining intensity was scored as: 0, 1, 2, and 3 for no, mild, moderate, and intense staining, respectively. The percentage score was classified as: 1, 2, and 3 for 1% to 33%, 34% to 66%, and 67% to 100% positivity, respectively. The product score was calculated. Totally, 86 patients were included in the study. Results The NAMPT staining scores were significantly higher in the CIN 2-3 group compared to the group with CIN 1/normal (90% vs 9%; respectively, P  &lt; .000). No intense NAMPT staining was observed in any of the specimens with CIN 1 or normal results. The percentage score of 2 to 3 was seen in 83% and 12% for patients with and without CIN 2-3, respectively ( P  &lt; .000). Using a cutoff value for product score of 2, the test demonstrated a sensitivity, a negative-predictive value, a specificity, and a positive-predictive value of 96%, 98%, 80%, and 71%, respectively. Although the product score was 2 and higher for 96% of CIN 2-3 specimens, 78% of those with CIN 1 or normal results had that below 2. Conclusion The NAMPT staining differs significantly among groups and may be a useful marker for distinguishing CIN 2-3 from normal tissue and CIN 1. That has potential to improve the sensitivity–specificity of diagnosing and treating cervical premalignant lesions.

The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors

Primary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. Seventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. Mutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). p53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Defining the relationship between ovarian adult granulosa cell tumors and synchronous endometrial pathology: Does ovarian tumor size correlate with endometrial cancer?

Abstract Objective The main feature of adult granulosa cell tumors (AGCT) is their capacity to secrete hormones, with nearly all of them capable of synthesizing oestradiol. The primary goal of this study is to identify synchronized endometrial pathologies, particularly endometrial cancer, in AGCT patients who had undergone a hysterectomy. Materials and Methods The study cohort comprised retrospectively of 316 AGCT patients from 10 tertiary gynecological oncology centers. AGCT surgery consisted of bilateral salpingo‐oophorectomy, hysterectomy, peritoneal cytology, omentectomy, and the excision of any suspicious lesion. The median tumor size value was used to define the relationship between tumor size and endometrial cancer. The relationship between each value and endometrial cancer was evaluated. Results Endometrial intraepithelial neoplasia, or hyperplasia with complex atypia, was detected in 7.3% of patients, and endometrial cancer in 3.1% of patients. Age, menopausal status, tumor size, International Federation of Gynecology and Obstetrics stage, ascites, and CA‐125 level were not statistically significant factors to predict endometrial cancer. There was no endometrial cancer under the age of 40, and 97.8% of women diagnosed with endometrial hyperplasia were over the age of 40. During the menopausal period, the endometrial cancer risk was 4.5%. Developing endometrial cancer increased to 12.1% from 3.2% when the size of the tumor was &gt;150 mm in menopausal patients ( p  = 0.036). Conclusion Endometrial hyperplasia, or cancer, occurs in approximately 30% of AGCT patients. Patients diagnosed with AGCT, especially those older than 40 years, should be evaluated for endometrial pathologies. There may be a relationship between tumor size and endometrial cancer, especially in menopausal patients.

Prognostic factors of adult granulosa cell tumors of the ovary: a Turkish retrospective multicenter study

To define the clinical, histopathological features and the prognostic factors affecting survival in patients with adult granulosa cell tumors of the ovary (AGCT). A 322 patients whose final pathologic outcome was AGCT treated at nine tertiary oncology centers between 1988 and 2021 participated in the study. The mean age of the patients was 51.3±11.8 years and ranged from 21 to 82 years. According to the International Federation of Gynecology and Obstetrics 2014, 250 (77.6%) patients were stage I, 24 (7.5%) patients were stage II, 20 (6.2%) patients were stage III, and 3 (7.8%) were stage IV. Lymphadenectomy was added to the surgical procedure in 210 (65.2%) patients. Lymph node involvement was noted in seven (3.3%) patients. Peritoneal cytology was positive in 19 (5.9%) patients, and 13 (4%) had metastases in the omentum. Of 285 patients who underwent hysterectomy, 19 (6.7%) had complex hyperplasia with atypia/endometrial intraepithelial neoplasia, and 8 (2.8%) had grade 1 endometrioid endometrial carcinoma. It was found that 93 (28.9%) patients in the study group received adjuvant treatment. Bleomycin, etoposide, cisplatin was the most commonly used chemotherapy protocol. The median follow-up time of the study group was 41 months (range, 1-276 months). It was noted that 34 (10.6%) patients relapsed during this period, and 9 (2.8%) patients died because of the disease. The entire cohort had a 5-year disease-free survival (DFS) of 86% and a 5-year disease-specific survival of 98%. Recurrences were observed only in the pelvis in 13 patients and the extra-abdominal region in 7 patients. The recurrence rate increased 6.168-fold in patients with positive peritoneal cytology (95% confidence interval [CI]=1.914-19.878; p=0.002), 3.755-fold in stage II-IV (95% CI=1.275-11.063; p=0.016), and 2.517-fold in postmenopausal women (95% CI=1.017-6.233; p=0.046) increased. In this study, lymph node involvement was detected in 3.3% of patients with AGCT. Therefore, it was concluded that lymphadenectomy can be avoided in primary surgical treatment. Positive peritoneal cytology, stage, and menopausal status were independent prognostic predictors of DFS.