The evaluation of miR-1181 and miR-4314 as serum microRNA biomarkers for epithelial ovarian cancer diagnosis and prognosis.

AIM: Epithelial ovarian cancer (EOC) is the most ominous tumor of gynecological cancers due to its poor early detection rate and unfavorable prognosis. To date, there is no reliable screening method for the diagnosis of ovarian cancer at an early stage. MiRNAs are small non-coding RNA molecules, and their main function is to regulate gene expression. The present study compared the serum miR-1181 and miR-4314 levels in patients with EOC and healthy controls to measure the diagnostic and prognostic value as candidate biomarkers. MATERIALS AND METHODS: We collected serum samples from a total of 135 participants (69 patients with EOC and 66 healthy controls). Relative expressions of miR-1181 and miR-4314 were measured by quantitative real-time polymerase chain reaction assay (qPCR). RESULTS: The present study revealed that both serum miR-1181 and miR-4314 levels in patients with EOC were significantly increased compared to healthy controls for each marker. In addition, there was a significant relationship between miR-1181 and miR-4314 overexpressions and the stage and prognosis of the disease. Finally, patients with high expression levels of miR-1181 and miR-4314 had significantly shorter survival rates than those with low expression levels. CONCLUSION: The current study proposed that serum miR-1181 and miR-4314 could discriminate the EOC patients from healthy controls. In addition, both miR-1181 and miR-4314 may be predictive biomarkers for ovarian cancer prognosis. Further studies are needed to confirm the findings of the present study.

Sentinel lymph node biopsy with carbon dye in endometrial cancer: a single center, prospective cohort study.

BACKGROUND: Many agents have been used for the detection of sentinel lymph nodes in endometrial cancer. Carbon dye, which has a strong staining ability and high contrast due to its dark black color, identifies the lymph nodes efficiently. Our aim was to evaluate the safety and efficacy of carbon dye for the detection of sentinel lymph nodes in endometrial cancer. METHODS: We conducted a single-center, prospective, cohort study in 89 patients with early-stage endometrial cancer between September 2021 and August 2022. The procedure was performed under laparoscopy. RESULTS: The sensitivity and negative predictive value of the sentinel lymph node biopsy (SLNB) with carbon dye injection were 83.3% and 98.8%, respectively. Mapping identified at least one sentinel lymph node in 84 patients (94.4%) on one pelvic side and at least one sentinel lymph node in 73 patients (82.0%) on each pelvic side out of 89 patients. In addition, no carbon dye-associated allergic reaction was detected. CONCLUSION: Carbon dye is a non-allergenic, inexpensive, and effective agent for SLNB with a satisfying sensitivity and a negative predictive value. In addition, both unilateral and bilateral detection rates were sufficient. Accordingly, carbon dye may be a promising tracer and a considerable option, particularly for low-income countries.

Central nervous system metastasis in gynecologic cancers: Seeking the prognostic factors.

OBJECTIVE: Central nervous system (CNS) metastasis originating from gynecological cancer is a very rare and late manifestation of the disease. Therefore, there is still limited data on prognostic factors for survival. The objective of the present study is to identify prognostic factors for survival in patients with CNS metastasis originating from gynecological cancer. STUDY DESIGN: The present retrospective study analyzed the patients with gynecological cancers who were treated due to CNS metastases between January 1999 and December 2019 at Istanbul University Hospital. RESULTS: Forty-seven patients with CNS metastasis of gynecological origin were included in the study. The median age at the time of CNS metastasis was 59 (range 34-93). The median time from initial cancer diagnosis to CNS metastasis was 24.9 (range: 0-108.2) months. Most patients had epithelial ovarian cancer (EOC) (76.6%), followed by endometrial cancer (EC) (14.8%), cervical cancer (CC) (4.3%), and vulvar cancer (VC) (4.3%). By multivariate analysis, the presence of extracranial metastasis (HR: 5.10; 95% CI: 1.71-15.18), Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (HR: 2.92; 95% CI: 1.36-6.26), palliative care only for the treatment of CNS metastasis (HR: 1.47; 95% CI: 0.58-4.11), and treatment-free interval (TFI) <6 months (HR: 2.74; 95% CI: 1.23-6.08) were independent factors that associated with worse survival. CONCLUSION: Patients with CNS metastasis who have favorable prognostic factors are considered to be appropriate candidates for aggressive and long-term treatment strategies. Extracranial metastasis, ECOG performance status, treatment history of CNS metastasis, and TFI were determined as independent prognostic factors that improved survival. TFI might be taken into account as a prognostic factor for patients with CNS metastasis in gynecological cancer.

Predictors of high-grade residual disease after repeat conization in patients with positive surgical margins.

OBJECTIVES: No consensus exists on the subsequent management strategy of patients who exhibit positive surgical margin (PSM) after re-excision of high-grade cervical intraepithelial neoplasia (CIN). The aim of the study is to examine the predictors related to the persistence of high-grade CIN lesions after re-excision, where PSM was left behind. MATERIAL AND METHODS: The present retrospective study included patients with PSM who underwent repeated conization due to residual high-grade CIN lesions between January 2005 and December 2019. The SPSS software v20.0 was used for data interpretation and statistical analysis. P values less than 0.05 were accepted as statistically significant. RESULTS: Repeat conization was performed in 91 patients, 43 (47.3%) presented with PSM with high-grade CIN, 6 (6.5%) presented with micro-invasive carcinoma, and 42 (46.2%) presented with clear surgical margin or CIN 1 at the surgical margin. At the time of conization, patients who presented with lesions > 5 mm in repeat cone specimens, exhibited a significantly higher rate of residual disease (p < 0.001). Besides, the involvement of the endocervical margin with high-grade CIN was the predictor of residual disease in repeat cone specimens (p = 0.006). CONCLUSIONS: In the cone specimen, the presence of lesion size greater than 5 mm and involvement of the endocervical margin were the predictors of high-grade residual disease after re-excision. Whether it is the first or second procedure, great care must be given to excise the lesion entirely at the time of the conization, preferably in one piece.

Prolongation of Neoadjuvant Chemotherapy before Surgery: Seeking the Optimal Number of Cycles in Serous Ovarian Cancer.

AIM: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival. METHODS: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C). RESULTS: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles. CONCLUSIONS: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery.

Skeletal system as a rare metastatic site in patients with ovarian carcinoma.

OBJECTIVE: To evaluate the frequency and predictors of bone metastasis in patients with ovarian cancer and to determine prognostic factors associated with this finding. METHODS: Patients diagnosed with ovarian cancer between January 2009 and December 2019 were evaluated. Patients with radiologically or pathologically confirmed bone metastasis were included in the study. Survival was analyzed using Kaplan-Meier curves and compared using the log-rank test. Multivariate analysis of prognostic factors related to survival was performed using the Cox proportional hazards model. RESULTS: Nineteen (2.6%) of 736 patients had bone metastases. Patients with clear cell histology had a higher risk of bone metastases than patients with the other epithelial histology groups (12.3% vs 2.1%, p<0.001). Overall survival was significantly lower in patients diagnosed with bone metastasis at the time of cancer diagnosis than in those diagnosed with bone metastasis during the course of the disease (median 63 vs 6.1 months, p<0.001). However, when the survival time after the development of bone metastasis was examined, no difference was found between patients with metastasis at the time of diagnosis and at the time of first or later progression (median 13.6 vs 4 months, p=0.09). In addition, the median survival of patients with clear cell histology after bone metastasis did not differ statistically from that of patients with other epithelial histology (median 22 vs 7.5 months; p=0.13). In the clear cell subgroup, bone metastasis was an independent prognostic factor for survival after multivariate analysis. For all patients, the stage at diagnosis and serum CA125 and alkaline phosphatase levels at the time of bone metastasis were prognostic factors for survival. DISCUSSION: Bone metastasis is rare in patients with ovarian cancer. However, the risk of bone metastasis is highest in patients with clear cell histology.

A Retrospective Clinical Analysis of Hyperthermic Intraperitoneal Chemotherapy in Gynecological Cancers: Technical Details, Tolerability, and Efficacy.

OBJECTIVE: The aim of this study was to reveal the results of hyperthermic intraperitoneal chemotherapy (HIPEC procedure) performed during cytoreductive surgery (CRS) in patients with endometrial cancer and epithelial ovarian cancer which included mainly platinum-resistant patients. METHOD: Patients who underwent CRS+HIPEC between May 2015 and January 2020 were evaluated retrospectively. Surgical complications were graded according to the Clavien-Dindo classification. RESULTS: A total of 33 CRS+HIPEC procedures were performed in 32 patients, two of whom had recurrent endometrial cancer. Of the 30 patients with epithelial ovarian cancer (EOC), five underwent interval CRS+HIPEC, and remaining 25 patients underwent secondary CRS+HIPEC treatment due to relapsed disease. Eighteen of the patients with relapsed disease were platinum-resistant. The overall operative mortality and severe morbidity rates were %3 and 12%, respectively. For 30 patients with EOC, during a median follow-up period of 15 months, Kaplan-Meier survival analysis revealed a 1-year OS and PFS rates of 69.7% and 30.3%, respectively. Moreover, in the subgroup analysis of the platinum-resistant cohort, median OS and PFS were 14 and five months, respectively. CONCLUSION: CRS+HIPEC procedures had acceptable severe morbidity and mortality rates. In addition, patients with recurrent EOC and without a visible residual disease at the end of cytoreductive surgery had, though not statistically significant, longer OS . HIPEC administration during CRS was not associated with adverse outcomes in the platinum-resistant EOC cohort. The short-term results of the current study are promising.

Clinicopathologic and survival results in serous endometrium carcinoma and subgroup analysis for mixed serous and pure serous histology.

OBJECTIVE: To review the clinicopathologic and survival outcomes of patients with serous endometrial cancer (EC) and to investigate subgroup analysis based on pure serous and mixed serous EC subtypes. MATERIAL AND METHODS: Patients who underwent EC surgery between 2002 and 2014 and who were reported as serous EC were enrolled in the study. All patients were diagnosed as having serous EC or mixed serous EC with serous component higher than 10% based on the postoperative pathology report. RESULTS: A total of 93 patients were analyzed. The median disease-free and overall survival (OS) durations were 49.6 and 32.2 months, respectively. Forty-three patients (46.2%) relapsed and 35 patients (37.6%) died. The histologic type was pure serous EC in 52 (55.9%) and mixed EC in 41 (44.9%) patients. There was no statistical difference between the pure serous and mixed serous groups in terms of age, International Federation of Gynecology and Obstetrics stage, lymphadenectomy, lymph node metastasis or adjuvant therapy combinations. Twenty-nine (55.8%) patients in the pure serous group and 14 (34.1%) in the mixed serous group hade recurrence (p=0.038). Twenty-five (48.1%) patients in the pure serous group and 10 (24.4%) in the mixed serous group died (p=0.034). In the pure serous group, the mean disease-free and OS durations were shorter than in the mixed serous group (59 vs. 81 months and 73 vs. 95 months, log-rank p=0.055 and 0.041, respectively). Histologic type was a significant prognostic factor on recurrence and OS in the univariate analysis (Hazard ratio: 2.404, 95% Confidence interval: 1.01-5.71; 2.027, respectively), but not in the multivariate analysis, which included disease stage and age of the patients. CONCLUSION: Compared with pure serous and mixed serous endometrium cancer groups, primary surgical treatments, clinicopathologic features and adjuvant treatments were similar, but there was a survival difference. Patients with pure serous cancer had a worse prognosis. However histology was not an independent factor for survival.

Maternal and fetal adropin levels in gestational diabetes mellitus.

AIM: To evaluate maternal and cord blood serum adropin concentrations in pregnant women with gestational diabetes mellitus (GDM). STUDY DESIGN: Twenty pregnant women with GDM and 20 gestational age-matched healthy pregnant women participated in the study. Maternal serum and cord blood adropin levels were assessed using an enzyme immunosorbent assay, at the time of birth. The relation of maternal serum and cord blood adropin levels with metabolic parameters were also assessed. RESULTS: The mean maternal and cord serum adropin in the GDM group were significantly lower than those of the control women (P=0.01 and P<0.001, respectively). Maternal serum adropin levels did not correlate with either fetal serum adropin levels or maternal metabolic values. CONCLUSION: The data suggest that low adropin levels may contribute to the underlying pathogenesis of GDM.

Salusins, newly identified regulators of hemodynamics and mitogenesis, increase in polycystic ovarian syndrome.

In the current study, we aimed to investigate whether serum salusin α and ß levels are different in PCOS subjects. Fifty women with PCOS and 50 healthy, age- and body mass index matched controls were included to the prospective cross-sectional study. All subjects underwent venous blood drawing on the early follicular phase after an overnight fasting. Serum salusin α and ß levels were measured with EIA, and ELISA respectively. The relationships between serum salusin levels and anthropometric and metabolic parameters were also assessed. Plasma salusin α and ß levels were higher in women with PCOS compared to control group. Serum salusin α level correlated positively with salusin ß and fasting serum insulin levels. The serum salusin ß levels were correlated positively with HOMA-IR, TG, LDL-C, LH, FSH, and total testosterone levels. Our results indicate that salusins, newly identified regulators of hemodynamics and mitogenesis, are increased within the serum of women with PCOS.

Maternal and fetal serum orexin-A levels in gestational diabetes mellitus.

AIM: Evidence suggests that orexin regulates food consumption, glucose metabolism and insulin secretion. Orexin may have a role in the pathogenesis of type II diabetes mellitus, however its role in gestational diabetes mellitus is not known. We aimed to assess maternal serum and cord blood orexin-A (OXA) concentrations in pregnant women with gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Thirty-five pregnant women with GDM and 35 gestational-age-matched healthy pregnant subjects participated in the study. Maternal serum and cord blood OXA levels were measured with enzyme immunoassay at the time of birth. The correlations between maternal serum and cord blood OXA levels, anthropometric and metabolic parameters were also assessed. RESULTS: The mean maternal and cord serum OXA (1.16±0.37 and 1.35±0.20ng/mL, respectively) in the GDM group were significantly different from those of the controls (1.58±0.59 and 1.25±0.21ng/mL, respectively). The mean maternal fasting-glucose-to-OXA ratio was significantly higher in the GDM group. In the GDM group, the mean maternal serum OXA levels were similar in the insulin (n=24) and diet (n=11) treated cases, respectively (1.13±0.36ng/mL and 1.21±0.41ng/mL). Maternal serum OXA levels positively correlated with fetal serum OXA and maternal glucose levels. OXA concentrations in maternal serum were negatively correlated with the fasting glucose, fasting insulin and homeostasis model assessment insulin resistance index. CONCLUSIONS: Maternal serum OXA levels decrease, and fetal serum OXA levels increase in women with GDM.

A comparative study on oxidative and antioxidative markers of serum and follicular fluid in GnRH agonist and antagonist cycles.

OBJECTIVE: To determine whether concentrations of oxidative stress markers of follicular fluid and serum are different in GnRH agonist protocol from GnRH antagonist protocol. MATERIAL AND METHOD: This was a cross-sectional study. Eighty-four women undergoing controlled ovarian stimulation with either GnRH agonist (n = 39) or GnRH antagonist protocols (n = 45) for IVF/ICSI treatment were assigned by a physician. Blood was obtained at the time of oocyte retrieval, and follicular fluid (FF) from the mature follicles of each ovary was centrifuged and frozen until analysis. Malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), hydroxyl proline (OH-P), sodium oxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), adenosine deaminase (ADA) and xanthine oxidase (XO) were assessed in the serum and follicular fluid of each participants. RESULTS: The mean serum concentrations of GSH-Px, GSH and MDA were lower in the GnRH antagonist group compared to GnRH agonist group, but mean serum SOD was higher in the GnRH antagonist group. The mean follicular SOD, ADA and NO were higher in GnRH antagonist group than GnRH agonist group. The IVF/ICSI outcomes were similar in both groups. CONCLUSION(S): GnRH antagonist protocol is associated with increased oxidative stress. The relation of GnRH analogues with oxidative stress and its implication in follicular growth needs to be addressed in further studies.

Changes in serum obestatin, preptin and ghrelins in patients with Gestational Diabetes Mellitus.

OBJECTIVES: The present study aims to establish the levels of acylated ghrelin, desacylated ghrelin, obestatin and preptin, during pregnancy and the postpartum period in pregnant women with Gestational Diabetes Mellitus (GDM) and healthy pregnancy women. DESIGN AND METHODS: The study registered 20 pregnant women with GDM and 20 healthy pregnant women. Fasting venous blood samples were collected from all cases between weeks 24 and 28 of pregnancy and after 24h postpartum. Hormones were analyzed using ELISA method. RESULTS: Serum acylated ghrelin (p:0.001), desacylated ghrelin (p:0.001), obestatin (p:0.006) and preptin (p:0.001) levels were all found statistically higher in both groups during the postpartum period, when compared to the pregnancy period. A positive correlation was established between desacylated ghrelin and acylated ghrelin (p:0.008), desacylated ghrelin and preptin (p:0.012) and preptin and insulin (p:0.039) in the GDM group during pregnancy. CONCLUSIONS: The studied hormones (especially desacylated ghrelin and obestatin) are critical in GDM pathophysiology based on the comparison of measure after and before the delivery.

Surgical termination of pregnancy: evaluation of 14,903 cases.

OBJECTIVE: To evaluate the demographic and clinical characteristics of patients who underwent surgical termination of pregnancy and to assess the efficacy of the termination methods. MATERIALS AND METHODS: This retrospective study was carried out on 14,903 healthy women who had intrauterine pregnancy of