Gunsu Kimyon Comert

Advanced stage, elevated mFIB-4 score, and MMR gene loss as independent predictors of oncological outcomes in endometrioid endometrial cancer: A retrospective observational study

This study aimed to evaluate the association between noninvasive liver fibrosis and steatosis scores (including the aspartate transaminase to alanine transaminase ratio to platelet ratio index, aspartate transaminase-platelet ratio index [APRI], Fibrosis-4 index, modified Fibrosis-4 index [mFIB-4], and hepatic steatosis index) as well as ultrasonographic steatosis scores (USS), with histopathological features of endometrioid-type endometrial cancer (EC) and their potential impact on survival outcomes. This retrospective observational study included 415 patients diagnosed with endometrioid-type EC who underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. Preoperative metabolic scores, including aspartate transaminase to alanine transaminase ratio to platelet ratio index, APRI, Fibrosis-4 index, mFIB-4, and hepatic steatosis index, were calculated from blood samples. USS and the diagnosis of metabolic dysfunction-associated fatty liver disease were based on liver imaging and metabolic criteria. Disease-free survival and overall survival were analyzed; significance was set at P  < .05. Analysis showed that patients with body mass index <30 kg/m 2 had higher rates of deep myometrial invasion (44.8% vs 27.3%, P  = .014), serosal invasion (6.9% vs 0.6%, P  = .017), lympho-vascular space invasion (34.5% vs 15.8%, P  = .002), and MSH6 loss (9.8% vs 1.4%, P  = .014) compared to obese patients. USS correlated with age, myometrial invasion depth, and PMS2 loss. Myometrial invasion >1/2 was more frequent in patients with mFIB-4 > 0.19 (37.5% vs 29%, P  = .048). Lower APRI (≤0.19) was related to the higher rate of cervical stromal invasion (15.8% vs 9.1%, P  = .027), lympho-vascular space invasion (29.7% vs 17.7%, P  = .002), adnexal involvement (11.3% vs 5.6%, P  = .026), and lymph node metastasis (24.1% vs 12.8%, P  = .009). Multivariable analysis showed advanced stage (HR = 5.172, P  < .001) and presence of at least one mismatch repair gene defect (HR = 2.936, P  = .011) independently predicted poor disease-free survival. Advanced stage (HR = 7.519, P  < .001) and a high mFIB-4 score (HR = 2.281, P  = .020) independently predicted worse overall survival. In conclusion, advanced stage remains the most significant independent predictor of poor oncological outcomes in endometrioid-type EC. Furthermore, this study highlights the prognostic relevance of metabolic dysfunction in this patient group. Noninvasive liver fibrosis markers (particularly mFIB-4 and APRI) were significantly associated with adverse histopathological features and survival outcomes, suggesting their potential role in risk stratification and prognosis assessment in endometrioid-type EC.

Does neoadjuvant chemotherapy reduce surgical complexity in patients with advanced-stage epithelial ovarian cancer?

Abstract Background This study aimed to determine the effect of neoadjuvant chemotherapy (NACT) on the complex surgical procedures required in addition to staging surgery for the need to achieve a residual tumor 1 cm or less in a population of stage IIIC–IV epithelial ovarian cancer patients. Methods Patients were referred for NACT if preoperative imaging and/or intraoperative evaluation confirmed that it was not possible to achieve a residual tumor size of 1 cm or less with cytoreductive surgery or if the patient had a poor performance status and a high American Society of Anesthesiologists (ASA) score. Surgical complexity was defined as complex or non-complex. Results One hundred and twenty-six patients with stage IIIC–IV ovarian cancer were included in the study. Primary cytoreductive surgery was performed in 67 patients, and interval cytoreductive surgery was performed in 59 patients after NACT. At least one complex surgery was performed in 74.6% of the patients in the primary cytoreductive surgery group and in 61% of the patients in the NACT group, with no statistically significant difference between the groups. However, the NACT group showed significantly decreased rates of low-rectal resection, diaphragmatic peritoneal stripping, and peritonectomy. Conclusions The analyses showed no reduction in the requirement for at least one complex surgical procedure in the group of patients who underwent NACT. Nevertheless, this group exhibited a significant decrease in low-rectal resection, diaphragmatic peritoneal stripping, and peritonectomy due to their effectiveness in reducing peritoneal disease.

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 (

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study

AbstractAimThe aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group.MethodsOut of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease‐free survival (DFS), and disease‐specific survival.ResultsThe 5‐year DFS of the study cohort was 89%, and the 10‐year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS.ConclusionAdjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Transdiaphragmatic cardiophrenic lymph node resection in a patient with an advanced-stage ovarian cancer

Spotlight on oncologic outcomes and prognostic factors of pure endometrioid ovarian carcinoma

To determine the prognostic factors related to recurrence and survival, and to evaluate the need for adjuvant chemotherapy in patients with endometrioid type epithelial ovarian cancer (EEOC). This study included 63 EEOC patients who were surgically staged. The FIGO 2014 stage was stage I in 41 (65 %) patients, stage II in 8 (12.5 %) patients, stage III in 14 (22.5 %) patients. 5-year failure-free survival (FFS) was 78 % in the entire cohort. 15 (23.8 %) patients had disease failure. In univariate analysis, advanced stage (II&III), high grade tumor, presence of ascites, bilateral tumor, presence of omental metastasis, positive peritoneal cytology were prognostic factors for poor FFS. Only the stage was determined to be an independent prognostic factor for disease-failure. According to multivariate analysis, stage II&III was related to a statistically significant hazard ratio for a disease failure of 3.49 (95 % confidence interval: 1.029-11.841; p = 0.045). The effectiveness of adjuvant chemotherapy was assessed for 41 patients with stage I. Eleven (26.8 %) patients with stage I did not receive adjuvant chemotherapy. Whereas 5-year FFS was 88 % in patients receiving adjuvant chemotherapy, that was 91 % in patients without adjuvant chemotherapy (p = 0.923). The independent prognostic factor for recurrence in EEOC was stage only. Adjuvant chemotherapy was not related to improvement in FFS in the early stage EEOC that were completely staged.

The effect of adjuvant radiotherapy on oncological outcomes in patients with early-stage cervical carcinoma with only intermediate-risk factors: a propensity score matching analysis

We aimed to evaluate whether adjuvant radiotherapy had a survival benefit for patients with early-stage cervical carcinoma with intermediate-risk factors. This study included patients who underwent radical hysterectomy and lymphadenectomy according to Wertheim-Okabayashi for stage IB1-IIA2 cervical carcinoma. Each patient had at least one intermediate-risk factor including tumour diameter ≥4 cm, deep stromal invasion, and positive lymphovascular space invasion (LVSI). Patients with lymph node metastasis, parametrial invasion, and positive surgical margins according to the final paraffin section were excluded. In total, 183 patients were included. Seventy-three (39.9%) patients had one, 85 (46.4%) had two, and 25 (13.7%) had three intermediate risk factors. Sixty-seven (36.6%) patients received adjuvant radiotherapy. There was a statistically significant difference in terms of stage, LVSI, and endometrial/uterine invasion between the groups that did and did not receive adjuvant radiotherapy (

Oncologic outcome in patients with 2018 FIGO stage IB cervical cancer: Is tumor size important?

AbstractBackgroundTo evaluate the prognostic factors and oncologic outcome in patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB cervical cancer (CC) after radical hysterectomy and lymphadenectomy.Materials and MethodsThis study included 290 patients with type II or III radical hysterectomy + pelvic ± para‐aortic lymphadenectomy and 2018 FIGO stage IB1‐3 epithelial CC. Disease‐free survival (DFS) estimates were determinate by using the Kaplan–Meier method. Survival curves were compared using the log‐rank test. Multivariate analysis was performed using a Cox proportional hazards models.ResultsThe mean age of study cohort was 52 ± 10.25 years. Five‐year DFS was 93% in entire cohort. On univariate analysis, surgical border involvement (p = 0.007), lymphovascular space invasion (LVSI) (p = 0.040), uterine involvement (p = 0.040), and depth of cervical stromal invasion (p = 0.007) were found to have statistical significance for DFS. However, none of them were independent prognostic factors for the risk of recurrence. Tumor size according to 2018 FIGO staging criteria was not related with recurrence.ConclusionsSurgical border involvement, LVSI, depth of cervical stromal invasion, and uterine involvement were predictors for DFS on univariate analysis. Tumor size was not predicting to recurrence in patient with 2018 FIGO stage IB1‐3 CC.

Prognostic value of systemic inflammatory response markers in cervical cancer

We investigated the association between preoperative ratios of inflammatory markers and the prognosis in patients with invasive cervical cancer (CC). In this single-centre study, we retrospectively enrolled 163 CC patients who underwent radical hysterectomy between February 2008 and October 2018. Among the evaluated ratios, a high neutrophil-to-lymphocyte ratio (N/L) was significantly associated with deep stromal invasion and tumour size larger than 2 cm, whereas a high M/L was significantly related to advanced-stage CC (IB3-IIIC2), lymphatic metastasis (total) and pelvic lymph node metastasis (

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.

Impact of postoperative infection on changes in leucocyte levels in early postoperative period in patients undergoing splenectomy during cytoreductive surgery for gynaecological malignancy

In cytoreductive surgery for gynecological cancers, 13-25% of patients require splenectomy. Therefore, hematological parameters change in the post-splenectomy period, especially leucocytosis and thrombocytosis. In this study, we aimed to evaluate the changing of leucocyte and neutrophil between the groups with and without infection in the early postoperative period in patients who underwent splenectomy during cytoreductive surgery for gynecological cancer. This retrospective study included 96 patients who underwent splenectomy during cytoreductive surgery for gynecological malignancies. Leukocyte levels, CRP, procalcitonin, and platelet counts were recorded daily during the first five postoperative days. Postoperative infections were identified based on clinical and laboratory findings. Postoperative infection was observed in 23 patients (24.0%). On postoperative day 4, the mean leukocyte count was 13.2±4.5 ×10³/µL in infected patients vs. 9.8±3.2 ×10³/µL in non-infected patients (p=0.01). By day 5, leukocyte levels remained significantly elevated in the infection group (p<0.05). Leukocyte trends, especially between days 4 and 5, may serve as a practical marker for early postoperative infection in patients undergoing splenectomy during cytoreductive surgery.

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.

Surgery for patients with endometrioid-type endometrial cancer: is lymphadenectomy above the inferior mesenteric artery necessary?

The primary objective of this study was to identify the risk of metastasis to lymph nodes above the inferior mesenteric artery (IMA) in endometrioid-type endometrial cancer (EC) and the factors that influence metastasis. The study included patients who had been operated on for endometrioid-type EC in three gynecological oncology centers between 2007 and 2023. The supramesenteric lymph node (SM-LN) is the region between the left renal vein and the IMA, whereas the inframesenteric lymph node (IM-LN) is the region between the IMA and the aortic bifurcation, as determined by the level of the IMA. The study sample comprised 412 patients. The median number of lymph nodes excised per patient was 58. The median count was 37 for pelvic lymph nodes, 21 for para-aortic lymph nodes, 8 for IM-LN, and 13 for SM-LN. In the univariate analysis, the factors that were found to be statistically significant in determining SM-LN metastasis included tumor size, depth of myometrial invasion, uterine serosal invasion, lymphovascular space invasion (LVSI), cervical invasion, peritoneal cytology, adnexal metastasis, omental metastasis, non-nodal extrauterine metastasis, pelvic lymph node metastasis, and IM-LN metastasis. In the multivariate analysis, SM-LN metastasis was independently associated with tumor size, LVSI, pelvic lymph node metastasis, and IM-LN metastasis. In conclusion, in cases of intermediate-high risk EC, it is important to know that the disease spreads to SM-LN in 7.3% of patients. The efficacy of postoperative adjuvant treatment may be inadequate due to a lack of information regarding the SM-LN region.

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.