OBJECTIVE:Despite the multiple available treatment modalities, cervical cancer is one of the leading causes of mortality and morbidity among female gynecological cancers. Endoplasmic Reticulum (ER) is an effective organelle in ensuring cell homeostasis and is closely related to the development of cancer. Esculetin is a coumarin derivative that has anticancer, anti-inflammatory, antioxidant, and neuroprotective effects. Esculetin may have an anticancer effect by inducting apoptosis and ER stress. In this study, we evaluate that esculetin has an anti-tumor effect on human cervical cancer-derived (HeLa) cells via ER stress. MATERIALS AND METHODS:Esculetin was applied to the HeLa cells, and a viability test was performed using the methyl thiazolyl tetrazolium proliferation (MTT) assay. Expression levels of apoptotic genes and anti-apoptotic genes were determined by real-time polymerase chain reaction. The results were statistically evaluated. RESULTS:Analysis of the MTT assay detected that esculetin inhibited HeLa cell viability development. Based on Western blot and quantitative real-time polymerase chain reaction (qPCR) analyses, esculetin destroyed cervical cancer cells via the ER stress pathway. CONCLUSIONS:The results showed that esculetin may have a potent antitumoral effect. It can potentially be utilized in the pharmacological therapy of cervical cancer.

OBJECTIVE:Endometrium cancer (EC) is the most prevalent cancer affecting women in developed countries. There is debate about the need to perform lymphadenectomy in cases with a tumor diameter >2 cm. The aim of our study is to research the prediction of lymph node metastasis using tumor size in stage 1A endometrioid endometrium cancer (EEC). PATIENTS AND METHODS:The study enrolled cases operated in the clinic due to stage 1A EEC (FIGO 2009) from December 2010-2021. The correlations of age, age interval, parity, type of operation, tumor diameter, myometrial invasion, histological grade, and lymph node metastasis were statistically analyzed. The cut-off point for tumor size was determined with the ROC curve and Youden index. RESULTS:The study analyzed a total of 292 cases, and the mean age of cases was 62.3±10.0 years. Of the cases, 79.5% had histological grade 1, and 20.5% had grade 2. Myometrial invasion ≤50% was detected in 69.5%, and no myometrial invasion was detected in 30.5%. The mean tumor diameter was 34.0±18.0. Lymph node metastasis was identified in 6 cases (2.1%). Based on the tumor diameter cut-off value of 35 mm, sensitivity was 100%, and specificity was 50.3%. 116 cases with tumor diameter >35 mm and 176 with diameter ≤35 mm, and grade 2 histology and lymph node positivity were found statistically significant between these groups (respectively, p=0.012 and p=0.038). The lymph node metastasis risk was 0% in cases with tumor diameter ≤35 mm, while it was 5.2% in cases with tumor diameter >35 mm. CONCLUSIONS:The general approach in stage 1A EEC is not to perform lymphadenectomy. However, when the tumor diameter is noted, lymphadenectomy may be considered as the lymph node metastasis risk increases in cases with a tumor diameter of 35 mm or more. There is a need for more clinical studies on this topic.

OBJECTIVE:Shear Wave Elastography (SWE) is an objective quantitative ultrasound elastography technique that can demonstrate the stiffness of anatomical structures to aid in their detection and characterization. We aimed to evaluate the role of shear wave elastography in differentiating endometrial carcinoma from benign uterine pathologies in women with abnormal uterine bleeding. PATIENTS AND METHODS:This prospective study was conducted at our institution from January 2020 to April 2020. A hundred patients with endometrial sampling planned and SWE due to abnormal uterine bleeding were included in the study. According to the histopathological results of the patients, those with normal and atrophic endometrium results were defined as group I (control group), those with benign results such as polyps and endometrial hyperplasia were defined as group II, and those with endometrial cancers were defined as group III. RESULTS:After adjustment for age, a statistically significant difference was found in Emean (mean and adjusted mean) value between the study groups (F2.96=86.37, p<.001, η2=0.64). The post-hoc analysis was performed with a Bonferroni adjustment. The mean Emean value was found to be statistically significantly higher in group III (17.14±0.40) compared to group I (10.39±0.26) and group II (11.49±0.32) (p<0.001). In addition, a statistically significant difference was found between the benign and normal groups. CONCLUSIONS:As a new diagnostic technique in gynecology, elastography appears to be a valuable tool in differentiating malign endometrial pathologies from normal or benign endometrial pathologies in females with abnormal uterine bleeding.

Background: Medical malpractice is a significant global issue affecting various aspects of healthcare, including ethical, legal, and managerial perspectives. Defensive medicine, where physicians engage in excessive practices to avoid malpractice lawsuits, is prevalent. In Turkey, the impact of malpractice fears on obstetricians and gynecologists (OB/GYNs) has not been extensively studied. This study aims to investigate the frequency of medical malpractice lawsuits, defensive medicine practices, the prevalence of medical malpractice stress syndrome (MMSS), and potential preventive measures among OB/GYNs in Turkey.Methods: A cross-sectional survey was conducted with 212 OB/GYNs in Turkey, following ethical approval. Participants completed a questionnaire on their experiences with malpractice, defensive practices, and MMSS. The survey included sociodemographic questions, standardized scales for defensive medicine practices, and MMSS-related questions. Data were analyzed using SPSS 18 with a 95% confidence level.Results: The majority of participants were experienced professionals aged 30-39, predominantly female, and working in the public sector with limited subspecialty training. Defensive medicine was widespread, with 95.5% of participants engaging in such practices, and 79.2% reported altering their practice due to malpractice fears. Older age, female gender, extensive experience, private sector employment, and specific subspecialties were associated with higher defensive practices and MMSS.Conclusion: Defensive medicine is common among Turkish OB/GYNs, driven by malpractice fears. The study highlights the need for improved support systems, better legal protections, and educational interventions to address defensive practices and reduce malpractice-related stress.

- OBJECTIVE: To investigate lymph node (LN) size detected by Magnetic Res-onance Imaging (MRI) for prediction of LN in-volvement in locally advanced cervical cancer (LACC).PATIENTS AND METHODS: A total of 55 cas-es diagnosed with LACC (IIB-IVA FIGO 2018) be-tween 28 December 2010 and 30 October 2020 were evaluated in this retrospective study. LN in-volvement was evaluated in patients who under-went surgical staging and MRI. The prediction of LN involvement based on LN size on MRI was calculated statistically.RESULTS: The mean age of 55 patients was 56 (33-78) years. For the cases, 76.4% were stage IIB, 12.7% were stage III, and 10.9% were stage IVA. Squamous cell histological type was de-tected with a rate of 90.9%. The cut-off value for pelvic LN diameter on MRI in predicting pel-vic LN involvement was 18.5 mm, and the sensi-tivity and specificity values were calculated as 50.0% and 93.6%, respectively (p=0.027). The cut-off value for pelvic and para-aortic LN diam-eter on MRI in predicting pelvic and para-aortic LN involvement was 17.0 mm with a sensitivity of 41.7% and specificity of 88.4% (p=0.081).CONCLUSIONS: In LACC, prediction of LN in-volvement by LN diameter detected on MRI has moderate sensitivity and high specificity with a cut-off value of 17.0 mm.

OBJECTIVE:Human papillomavirus (HPV), which is known to play a very important role in genital area (vulva, vagina, and cervix) cancers in women, is responsible for almost all cervical cancers. However, a significant proportion of cervical carcinomas (approximately 7%) is HPV-negative. Therefore, there are still two important questions to be answered: 1. Why is HPV  Deoxyribonucleic acid (DNA) not found in all cervical carcinomas? 2. Are HPV-DNA-negative cervical cancers a specific subgroup of cervical cancers with different biological behavior (worse prognosis)? In this article, we aimed to evaluate the clinicopathological characteristics and survival of patients with confirmed HPV-negative tumors in order to answer these two questions. PATIENTS AND METHODS:A total of 97 patients who underwent HPV-DNA testing and received a histological diagnosis of cervical cancer were included in the study. 14 HPV-DNA negative and 83 HPV-DNA positive cervical carcinoma patients were detected. Demographic profiles, clinicopathological characteristics, progression-free, and overall survival of all patients were analyzed. RESULTS:Women with HPV-negative tumors were diagnosed at an older age range (p=0.05), and their demographic data other than age range were similar to HPV-positive tumors. P16 staining pattern was not observed in any of the HPV-negative tumors (p=0.001), and a positive P53 staining pattern was detected in 35.7% of the HPV-negative tumors. Although disease-free survival (PFS) (p=0.224) and overall survival (OS) (p=0.219) were worse in the HPV-negative patient group, this difference was not statistically significant. CONCLUSIONS:HPV-negative cervical cancers do not have a poor prognosis unlike their counterparts in other anatomical regions where HPV-associated tumors are present.

Objective: Immune responses to SARS-CoV-2 are the main cause of tissue damage in coronavirus disease 2019. However, the pathophysiological mechanism of the disease has not been fully elucidated. The aim of this study was to examine T cell subsets of pregnant women infected with SARS-CoV-2 and evaluate the relationship between the possible differences in trimesters and clinical findings of the disease.Materials and Methods: Fifty-six pregnant patients with SARS-CoV-2 and 61 healthy pregnant controls were included in the study. T cell subsets were analyzed by flow cytometry.Results: The CD3(+) total T cell (p = 0.006 and p = 0.027) of pregnant patients infected with SARS-CoV-2 in second and third trimesters was found to be lower than in the control group. CD3(+)CD4(+) helper T cell (p = 0.035), Treg (p = 0.001), and Treg/Th17 ratio (p = 0.001) were found to be lower in the third trimester patients infected with SARS-CoV-2 than in the controls. Significant decreases were observed only in the Treg (p = 0.001) and Treg/ Th17 ratio (p = 0.001) in the first trimester patients infected with SARS-CoV-2 compared to the controls. When trimesters were compared in terms of T subsets, no difference was found (p > 0.05).Conclusion: The CD3(+) total T cell (p = 0.001), CD3(+)CD4(+) helper T cell (p = 0.011), Treg (p = 0.001), and Treg/ Th17 ratio (p = 0.001) were found to be lower in pregnant women infected with SARS-CoV-2. This difference was associated with the development of pneumonia but not with adverse pregnancy outcomes.

OBJECTIVE: Sentinel lymph node biopsy refers to an innovative and minimalist surgical approach that has been introduced to reduce both complications and morbidity. A de-finitive answer to the question of whether lymph-adenectomy is performed for staging or curative purposes in endometrial cancer has not yet been found. The aim of this study is to compare patients who underwent sentinel lymph node biopsy with indocyanine green and those who under-went laparoscopic complete surgical staging in terms of survival. PATIENTS AND METHODS: A total of 182 patients was included in the study. The patients were divided into two groups according to the lymph node sample type. The two groups were compared in terms of oncological outcomes.RESULTS: 92 patients underwent sentinel lymph node mapping (SLNM cohort) and 90 patients underwent extensive pelvic and paraaortic lymphadenectomy (SCL cohort). Considering only patients with negative lymph nodes, the Sentinel cohort was associated with a reduced DFS and OS (p=0.008 and p=0.005, respectively). This dif-ference may be due to the longer follow-up times of patients with comprehensive lymph node sam-pling. On the other hand, There was no difference in survival in lymph node positive cases.CONCLUSIONS: Sentinel lymph node dissection has no negative effect on survival in lymph node positive patients.

Introduction/Background* Diagnostic efficacy of sentinel lymph node (SLN) biopsy is proven in many studies in terms of the detection of lymphatic spread in endometrial cancer. However, there are limited data about the effect of SLN biopsy only on survival. The aim of this study was to investigate whether SLN biopsy only compromises oncologic outcomes compared to systematic lymphadenectomy in a large cohort. Methodology In this multicentric study, records of 564 endometrial cancer patients who underwent surgical staging with either sentinel lymph node biopsy alone or sentinel lymph node biopsy followed by systematic lymphadenectomy with at least 6 months of follow-up time were retrospectively reviewed. The impact of type of lymphadenectomy and histopathologic factors on recurrence, disease-free survival (DFS) and overall survival (OS) were assessed. DFS and OS rates were calculated using Kaplan-Meier method and log-rank test was used to calculate statistical significance between the groups. Cox univariate and multivariate analyses were used to identify prognostic factors for DFS and OS. Result(s)* Median follow up time was 28 months (range: 6-130) and 14 (2.5%) of the 21 (3.7%) deaths were due to the disease. 2- and 3-year OS were 98.2% and 97%, respectively. Median time to recurrence was 12.5 months (range: 3-30). Sites of the 42 (7.4%) recurrences were as follows: 12 (28.6%) locoregional, 19 (45.2%) distant, 3 (7.1%) nodal and 8 (19%) more than one site. 2- and 3-year DFS were 93.1% and 92.6%, respectively. While non-endometrioid subtypes (p=0.048), grade 3 histology (p<0.001) and presence of lymphovascular space invasion (LVSI) (p<0.001) were found as independent prognostic factors for decreased DFS, age (p=0.017) and tumor size (p=0.041) were independent factors for shorter OS. Type of lymphadenectomy was not a prognostic factor lymphatic recurrence, DFS and OS. Conclusion* Our study showed that removal of only SLNs was not associated with worse survival compared to systematic lymphadenectomy in endometrial cancer patients. Nodal recurrence rate was also similar between the groups.

Introduction/Background* The aim of this study was to evaluate sensitivity, negative predictive value (NPV) and false negative rate (FNR) of sentinel lymph node (SLN) mapping algorithm in high-risk endometrial cancer patients. Methodology Patients with non-endometrioid histology, grade 3 endometrioid tumors and/or tumors with deep myometrial invasion were enrolled in this retrospective, multicenter study. After removal of SLNs, all patients underwent pelvic ± paraaortic lymphadenectomy. Operations were performed via laparotomy, laparoscopy or robotic surgery. Indocyanine green (ICG) and methylene blue (MB) were used as tracers. SLN detection rate, sensitivity, NPV and FNR were calculated. Result(s)* Two hundred forty-four patients were included. Surgeries were performed via open approach in 132 (54.1%) patients. While 92 (37.7%) patients underwent bilateral pelvic lymphadenectomy, 152 (62.3%) underwent both bilateral pelvic and paraaortic lymphadenectomy. ICG was used in 120 (49.2%) patients and MB in 124 (50.8%). At least 1 SLN was detected in 222 (91%) patients with a 65.6% bilateral detection rate. Fifty-five (22.5%) patients had lymphatic metastasis and 45 patients had at least 1 metastatic SLN: 28 macrometastasis, 6 micrometastasis and 11 isolated tumor cells. Lymphatic metastasis was detected by side-specific lymphadenectomy in 8 patients and 2 patients had isolated paraaortic metastasis. Overall sensitivity, NPV and FNR of SLN biopsy were 81.8%, 95% and 18.2%, respectively. By applying SLN algorithm steps, sensitivity and NPV improved to 96.4% and 98.9%, respectively. For grade 3 tumors, sensitivity, NPV and FNR of the SLN algorithm were 97.1%, 98.9% and 2.9%, respectively. Sensitivity, NPV and FNR of SLN algorithm were 95%, 98.9% and 5%, respectively in deep myoinvasive tumors. Conclusion* This study was performed in one of the largest high-risk endometrial cancer population. SLN algorithm was found to be safe and had high diagnostic accuracy also in high-risk endometrial cancer patients. Although it seems like SLN algorithm is a feasible option for staging, long term studies to determine impact of SLN biopsy alone on survival are needed before it becomes standard of care in high-risk endometrial cancer.

OBJECTIVE:We aimed to investigate the vasoactive effects of dexmedetomidine on isolated human umbilical arteries and possible mechanisms involved.METHODS:Human umbilical artery strips were suspended in Krebs-Henseleit solution and dose-response curves were obtained for cumulative dexmedetomidine before and after incubation with different agents; propranolol, atropine, yohimbine, prazosin, indomethacin, verapamil. Effects of calcium on cumulative dexmedetomidine-induced contractions were also studied.RESULTS:Cumulative dexmedetomidine resulted in dose dependent contraction responses. Incubation with propranolol (Emax: 93.3 ± 3.26 %), atropine (Emax: 92.0 ± 6.54 %), or indomethacin (Emax: 94.25 ± 2.62 %), did not attenuate dexmedetomidine-elicited contractions (p > 0.05). There were significant decreases in the contraction responses of cumulative dexmedetomidine with yohimbine (Emax: 12.1 ± 11.9 %), prazosin (Emax: 28.8 ± 4.6 %) and verapamil (Emax: 11.2 ± 13.6 %) (p < 0.05). In Ca+2 free medium contraction responses to cumulative dexmedetomidine was insignificant (Emax: 5.20 ± 3.42 %). Addition of cumulative calcium to the Ca+2 free medium resulted in concentration dependent increase in contractions (Emax: 64.83 ± 37.7 %) (p < 0.05).CONCLUSION:Dexmedetomidine induces vasoconstriction in endothelial-free umbilical arteries via both, α1- and α2-adrenergic receptors and also extracellular Ca+2 concentrations play a major role. β-adrenergic receptors, muscarinic cholinergic receptors, and inhibition of cyclooxygenase enzyme are not involved in this vasoconstriction (Fig. 3, Ref. 36).

Introduction/Background Vulvar intraepithelial neoplasia (VIN) is termed premalignant situation of the vulva.1 VIN incidence is about 1.4/100.000. Risk factors for VIN are Human Papilloma Virus (HPV) infection, HIV(Human İmmunodeficiency Virus) infection, other sexual transmitted diseases, smoking and other neoplasms.2 In 2015, İnternational Society for the Study of Vulvovaginal Disease(ISSVD) released that describes VIN; Low-grade squamous intraepithelial lesion(LSIL) of the vulva(HPV effect), High grade squamous intraepithelial lesion(HSIL) of the vulva (VIN usual type) and VIN differentiated type(dVIN).3 The increase of VIN usual type among younger patients is generally due to the infection of high risk HPV.4 The dVIN is seemed commonly in older women with a median age of 67,5 and is usually associated with skin disases like lichen sclerosus.Suspicious for malignancy or-premalignant lesions of the vulva may be excised in a conservative fashion, protecting as much of the vulvar architecture as possible.6 Cervical intraepithelial neoplasia is termed premalignant situation of the uterine cervix.7 HPV infection is considered the most important factor for the development of CIN and cervical cancer. High grade lesions have significant risk of disease progression to the cervical cancer and should be managed with conization. This will be therapeutic as well as diagnostic. Methodology Our patient was 42-years old and multiparous patient with main complaint of vulvar pruritus and genital condyloma.Her outer hospital vulvar and cervical-biopsy result was squamous carcinoma in situ for vulva and HSIL for cervix.We re-evaluated the pathology in our hospital. The biopsy revealed for cervix VIN 3. Then she underwent conization and vulvectomy with a 2 cm disease free-margin. Results After the excision procedure patient´s skinning vulvectomy pathology was VIN3, psoriasis, lichen sclerosis and conization pathology was LGSIL.Both surgical margins were clear. After the surgery there wasn´t any wound dehiscence, infection or abscess. Conclusion In VIN3 lesions skinning vulvectomy appears to be a favourable and safe treatment however the recurrence of VIN is frequent.8 It should-be applied carefully evaluated patients. Disclosure Thanks for your concern. References Reyes MC,Cooper K. Anupdateonvulvarintraepithelialneoplasia:terminologyand a practicalapproachtodiagnosis. J Clin Pathol 2014; 67:290. Iavazzo C,Pitsouni E,Athanasiou S,Falagas ME.Imiquimod for treatment of vulvar and vaginal intraepithelial neoplasia. Int J Gynecol Obstet 2008; 101:3–10. CrumCP,HerringtonCS,McCluggageWG,et al. Tumours of the vulva; epithelial tumours. In: WHO Classification of Tumours of Female Reproductive Organs, 4th ed, Kurman RJ, CarcangiuML,HerringtonCS,et al (Eds), IARC Press, Lyon 2014. ,et al. Tan J, Chetty N, Kondalsamy-Chennakesavan S, Crandon A, Garrett A, Land R. Validation of the FİGO 2009 staging system for carcinoma of the vulva. Int J Gynecol Cancer. 2012;22(3):498–502. JouraEA,GarlandSM,PaavonenJ,FerrisDG, Perez G, Ault KA, et al. Effect of the human papilloma virüs (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: retrospective pooled analysis of trial data. BMJ. 2012;344:e1401. von GruenigenVE,GibbonsHE,GibbinsK,et al. Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial. 2007Obstet Gynecol; 109:942. MontzFJ.Management of high-grade cervical intraepithelial neoplasia and low-grade squamous intraepithelial lesion and potential complications. 2000Clin Obstet Gynecol;43:394. WallbillichJJ,RhodesHE,MilbourneAM,et al.Vulvar intraepithelial neoplasia (VIN 2/3): comparing clinical outcomes and evaluating risk factors for recurrence. 2012Gynecol Oncol;127:312.

Paragangliomas are extremely rare neuroendocrine neoplasms with a reported incidence of 2–8 per million. They are chromaffin cell tumours that develop from neural crest cells in the autonomic nervo...