Turkish Journal of Medical Sciences

Survival of patients with 2014 FIGO stage IIIC high-grade serous ovarian cancer who treated with platin-based adjuvant chemotherapy

Epithelial ovarian cancer is the second most prevalent type of gynecological cancer. We aimed to investigate prognostic factors related to survival in patient with 2014 FIGO stage IIIC high-grade serous ovarian cancer (HGSOC). Two hundred fifty eight patients were evaluated retrospectively. The absence of a visible tumor was determined as maximum cytoreduction, and a residual tumor size of 1 cm or less was determined as optimal cytoreduction. Patients who underwent cytoreduction followed by a combination of platinum and taxane adjuvant chemotherapy were included. Exclusion criteria for the study were patients taking neoadjuvant chemotherapy and those with suboptimal surgery. Optimal cytoreduction was performed in 107 and maximal cytoreduction was performed in 151 patients. The five-year PFS rate was 27% and the five-year DSS rate was 76%. While high ascites volume and optimal cytoreduction were identified as independent prognostic factors for disease failure, only optimal cytoreduction was an independent prognostic factor for survival. The maximal cytoreduction is improves PFS and DSS in patients with 2014 FIGO stage IIIC HGSOC as our study results. Therefore, maximum surgical effort and radical cytoreductive procedures should be performed.

Coexisting growing teratoma syndrome and gliomatosis peritonei following ovarian immature teratoma: a case report and literature review

Growing teratoma syndrome (GTS) is characterized by a reduction in serum tumor markers despite the growth of a benign mature teratomatous mass following chemotherapy for germ cell tumors. Gliomatosis peritonei (GP) typically accompanies ovarian teratomas, marked by the dissemination of mature glial tissue across the peritoneum. The concurrent presence of GTS and GP after treatment for ovarian immature teratoma (IMT) is notably rare, with approximately 20 reported cases. This case involves a 25-year-old patient who underwent surgical removal of an adnexal mass, which was later diagnosed as stage IIIA grade 3 ovarian IMT with parametrial involvement. Following two cycles of bleomycin, etoposide, and cisplatin chemotherapy, imaging identified new lesions adjacent to the liver and on the pelvic peritoneum. A second fertility-sparing surgery was performed, and paraffin pathology confirmed a mature teratoma within the excised specimen. Additionally, the resected pelvic peritoneum revealed nodules of mature glial tissue consistent with GP. The coexistence of GP with GTS post-IMT surgery presents a diagnostic challenge in distinguishing between malignant and benign components, which is critical to avoid unnecessarily aggressive surgical and chemotherapeutic treatments. Recognizing such cases may enable fertility-sparing surgery for these patients.

The risk of cancer in patients with primary Sjögrensyndrome; A single-center study from Turkey

The aim of this study is to determine the risk of cancer in patients with primary Sjögren syndrome (pSS) from a single center in Turkey. Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific standardized incidence ratios (SIR) of solid and hematological cancers were calculated compared with the general population. Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n = 396, 92.1%), and the mean age was 58.6 ± 12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625-3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n = 6), ovarian cancer (n = 6), and non-Hodgkin lymphoma (NHL) (n = 4). There was an increased risk for ovarian cancer (SIR 12.76, 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature.

NNMT overexpression is an adverse prognostic factor in uterine leiomyosarcoma

Uterine leiomyosarcomas (uLMS) are extremely rare high-grade tumors with a poor prognosis. Their etiopathogenesis remains largely unknown. The uterus is the most frequent site for LMS. uLMS and uterine leiomyoma (uLM) must frequently be differentiated in patients with a uterine mass. Nicotinamide N-methyltransferase (NNMT), a cytoplasmic protein, is involved in the progression and spread of a variety of cancer types. The expression of NNMT in a mesenchymal malignancy was not examined previously. This study represents the first investigation into NNMT expression in uLMS, uLM and benign uterine myometrium and correlates NNMT overexpression with worse prognosis in uLMS. The expression of NNMT was investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue of uLMS in 31 patients, uLM in seven patients and benign myometrial in 31 patients. The expression of NNMT in uLMS was markedly higher than in uLM and normal myometrial tissue (p < 0.001). The expression of NNMT in early stage uLMS was lower than in advanced stage disease (p = 0.034). NNMT expression was an independent prognostic factor in predicting recurrence-free survival in uLMS (p = 0.037). NNMT can aid in the preoperative differentiation of uLMS and uLM. The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.

What is the predictive value of preoperative CA 125 level on the survival rate of type 1 endometrial cancer?

To investigate the utility of preoperative serum cancer antigen 125 (CA 125) levels in type 1 endometrial carcinoma (EC) as a marker for determining poor prognostic factors and survival. All patients with endometrial cancer, who had been treated between 2012 and 2020, were retrospectively reviewed, and finally, 256 patients with type 1 endometrium carcinoma were included in the study. The relationship between the clinicopathological characteristics, CA 125 level, and survival rates were analyzed. The cut-off value for the preoperative serum CA 125 level was defined as 16 IU/L. The median serum CA 125 levels were significantly higher in patients with deep myometrial invasion, lymph node metastasis, lymphovascular space invasion, cervical stromal and adnexal involvement, advanced stage, positive peritoneal cytology, recurrence, and adjuvant therapy requirement. Serum CA 125 cut-off values determined according to clinicopathologic factors ranged from 15.3 to 22.9 IU/L (sensitivity 61%–77%, specificity 52%–73%). The disease-specific survival rate was significantly higher in patients with CA 125 levels < 16 IU/L (P = 0.047). The data showed that choosing a lower threshold value for the CA 125 level (16 IU/L) instead of 35 IU/L, could be more useful in type 1 EC patients with negative prognostic factors.

Evaluation of metabolic uptake in gynecological organs using FDG-PET in women diagnosed with non-gynecological malignancies

Gynecological malignancies, including those affecting the uterus, cervix, vagina, vulva, and adnexa, pose significant physical and psychosocial burdens. Early detection and effective management of these malignancies are critical for improving outcomes. This study aims to evaluate metabolic uptake patterns in gynecological organs using fluorodeoxyglucose positron emission tomography (FDG-PET) and to analyze their malignancy potential in women with nongynecological cancers. A retrospective analysis was conducted on 221 women with nongynecological malignancies who exhibited pathological FDG uptake in gynecological organs on FDG-PET/CT imaging. Lesions were evaluated based on the standardized uptake value maximum (SUVmax), morphological characteristics on contrast-enhanced CT, and further gynecological assessment using ultrasonography, biopsy, and endometrial sampling. Statistical analyses, including the receiver operating characteristics curve and descriptive statistics, were performed using SPSS software, with significance set at p 10.11 predicted malignancy in uterine lesions with 86% sensitivity and 82% specificity. Among patients with uterine involvement, malignancy was confirmed in 10 cases, all of whom were on tamoxifen therapy. Endometrial thickness was significantly higher in malignancy cases (10.6 mm vs. 5.8 mm, p = 0.014). Ultrasonography and biopsy findings largely confirmed the benign nature of other lesions, highlighting the role of multimodal diagnostic approaches. FDG-PET imaging is a valuable tool for identifying metabolic activity in gynecological organs and for differentiating malignant lesions from benign ones. High SUVmax values and endometrial thickness are significant indicators of malignancy, particularly in patients undergoing hormonal therapy. This study underscores the importance of integrating metabolic imaging with clinical and morphological assessments for the early detection and management of gynecological malignancies.

Is advanced bipolar vessel sealing device really effective in decreasing the pelvic lymphocele ratio in open surgery for endometrial cancer?

We aim to show pelvic lymphocele (PL) rates in patients who were operated for endometrial cancer (EC) and underwent systematic paraaortic bilateral pelvic lymph node dissection (PABPLND) with advanced bipolar vessel sealing device (ABVSD). The medical files of all patients who underwent open surgery for EC between January 2017 and December 2021 were retrospectively analyzed. One hundred three patients who operated with the diagnosis of high-intermediate and high-risk endometrial cancer were included. Systematic PABPLND was performed with total abdominal hysterectomy with or without bilateral salpingo-oophorectomy during surgery to all patients. All operations were performed by same three surgeons who were expert in their field. While the lymph packages were removed during surgical dissection, the distal afferent and proximal efferent lymphatic channels were sealed with LigaSure™ blunt tip sealer/divider (Medtronic, Covidien, USA). The patients were scanned with computed tomography (CT) between 8 and 12 weeks postoperatively. Lymphocele diagnosis was confirmed by radiologists and largest diameter was recorded. Clinical-pathological findings of all patients were recorded. Mean age and body mass index (BMI) of all participants were 58.6 ±10.2 years and 28.1± 5.6 kg/m2 . The most histopathological findings were endometrioid type (84.5%) and grade 2 (44.2%) ECs. The pelvic lymphocele (PL) was detected with CT in 24 of 103 patients at 8 to 12 weeks postoperatively. Only two PL patients were symptomatic. The first patient had symptoms of pelvic fullness and compression while the second patient had infected image. PL was located to right pelvic area in first case while the second was located on the vaginal cuff. The dissection and sealing of major lymph vessels were achieved during the removal of all lymph packages with LigaSure™ blunt tip laparoscopic sealer/divider. The use of advanced bipolar systems can reduce the formation of PL in lymph node dissection in endometrial cancer.

Expression of laminin-1 and matrix metalloproteinase-9 in benign and malignant endometrium

Laminin-1 and matrix metalloproteinase (MMP)-9 may play roles in the progression from benign to malignant endometrium, so we aimed to investigate their levels of expression in these tissues. This case-control study was conducted at a tertiary care center between January 2014 and December 2016. Paraffin blocks of 50 specimens of benign endometrium with proliferative (n = 20), secretory (n = 11), and atrophic (n = 5) endometrium; simple endometrial hyperplasia without atypia (n = 12); and endometrial polyp (n = 2) histology and 49 specimens of malignant endometrium with endometrioid (n = 40), serous (n = 7), clear cell (n = 1), and undifferentiated (n = 1) types were immunostained with laminin-1 and MMP-9 antibodies and assessed for basement membrane continuity for laminin-1 and the percentage and intensity of MMP-9 expression in epithelial cytoplasm. : Laminin-1 continuity in the basement membrane was higher in benign (92%) compared to malignant (16.3%) endometrium (p 0.05). All atrophic endometria and endometrial polyps and 23.5% of low grade endometrioid and none of the other endometrial cancers showed uninterrupted basement membrane staining with laminin-1. All cases in malignant endometrium expressed MMP-9 with either low or high immunoreactivity while none of the cases in benign endometrium showed a high staining with MMP-9 (p < 0.01). Proliferative and hyperplastic endometrium together with grade 1 endometrioid cancer expressed MMP-9 better than the atrophic endometrium (p < 0.05). The immunoreactivity with MMP-9 increased gradually from secretory to hyperplastic endometrium and serous carcinoma (p < 0.05). MMP-9 expression in all types of cancers except grade 1 endometrioid and clear cell compared to proliferative endometrium was significantly higher (p < 0.05) and increased from proliferative to grade 2 endometrioid, grade 3 endometrioid, serous and undifferentiated endometrial carcinoma. Gradual increments in MMP-9 expression and basement membrane laminin-1 discontinuity may indicate progression from normal to hyperplastic and to low- and high-grade cancerous endometrium.

Is microcystic, elongated, and fragmented pattern of myometrial invasion in endometrioid endometrial carcinoma associated with survival?

Microcystic, elongated, and fragmented (MELF) pattern is one of the myometrial invasion patterns in endometrioid endometrial carcinoma (EEC), and it has been associated with poor prognostic parameters, especially lymphovascular space invasion (LVSI) and lymph node metastasis (LNM). This study aims to represent the frequency of MELF pattern in EEC and the relationship between MELF pattern with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS). In this retrospective cohort study, we examined 233 patients with EEC diagnoses with the result of a total hysterectomy and bilateral salpingo-oophorectomy between 2009 and 2014. The association of MELF pattern with risk factors such as stage, recurrence, and survival was analysed statistically with the comparison of MELF positive and negative cases. MELF pattern was seen in 21.8% of all cases (51/233) and 23% of grade 1-2 cases (50/217). The MELF pattern showed a significant difference among patients when they were compared according to advanced age (≥60) (p = 0.022), LVSI (p = 0.021), deep myometrial invasion (p < 0.01), LNM (p = 0.027), and advanced FIGO stage (p = 0.043). MELF pattern was a predictive factor of LNM in univariate logistic regression analysis but did not show significance in multivariate analysis. The Kaplan-Meier survival analysis showed that MELF positive cases had reduced OS (66.7% vs 79.7% p = 0.003) and DFS (66.7% vs 77.5% p = 0.017) rates. In the univariate analyses, MELF pattern was an independent prognostic factor on OS and DFS along with other parameters, while it was not observed to maintain this effect in the multivariate analyses. This study is one of the largest series examining the relationship between MELF pattern of myometrial invasion and survival, and our results represented that the MELF pattern is associated with the worse clinical outcome since it is associated with lymphovascular space invasion, deep myometrial invasion, lymph node metastasis, and reduced overall survival and disease-free survival rates. Although the presence of MELF pattern is not reported in routine practice, it may be used as an indicator that will help predict a worse outcome.

Response to Letter to the Editor

Radiomics analysis of uterine tumors in 18F-flourodeoxyglucose positron emission tomography for prediction of lymph node metastases in endometrial carcinoma

In this single-center study, we aimed to analyze texture features of primary uterine lesions on 18F-FDG PET/CT to predict lymph node metastases. Totally, 157 (mean age: 62 ± 10.2 years) patients were included in the analysis. Histopathological examination results were considered as the standard reference for nodal involvement. On 18F-FDG PET/CT images, only the primary tumor was segmented. SUVmax, SUVmean, SUVpeak, MTV, and TLG of primary uterine lesions were calculated for analyses. For texture analysis first, second, and higher-order texture features were calculated. Mean diameter of primary uterine lesions was calculated as 35± 18.1 mm. Lymph node metastases were detected in 19% of patients in histopathological examination of surgical materials. While 26 patients had pelvic lymph node metastases, 19 patients had additional paraaortic lymph node metastases. On radiomics analysis for 20 features, a significant difference was found between patients with and without lymph node metastasis. With using data mining methods GLZLM ZLNU, EntropyGLCM, Entropyhisto, GLRLM LRHGE, GLZLM HGZE, GLZLM SZHGE, GLRLM HGRE, GLRLM SRHGE were found significant radiomics features to predict lymph node metastasis with a diagnostic accuracy of 0.8. The radiomics analysis of intratumoral heterogeneity is a promising method for improving triage of the patients for lymph node dissection in endometrial carcinoma.

Conservative management of patients with endometrial intraepithelial neoplasia (EIN): Factors that could affect response and pregnancy rates.