Clinicopathological and Survival Characteristics of Mismatch Repair Status and PD-1 Expression in Serous Ovarian Cancer.

OBJECTIVE: To evaluate the clinicopathological characteristics of mismatch repair (MMR) deficiency and its clinical outcomes by performing immunohistochemistry (IHC) for MMR genes in the serous ovarian cancer (SOC) tumour sections. STUDY DESIGN: A retrospective case-control study. Place and Duration of the Study: Gynecology Department of Kanuni Sultan Süleyman Training and Research Hospital, and Department of Medical Oncology of Medipol University, between March 2001 and January 2020. METHODOLOGY: IHC was carried out for MLH1, MSH2, MSH6, and PMS2 on full-section slides from 127 SOCs to evaluate the MMR status. MMR-negative and MMR-low groups together were defined as MMR deficient and called microsatellite instability-high (MSI-H). The MSI status and expression of programmed cell death-1 (PD-1) were compared in SOCs with different MMR statuses. RESULTS: A significantly higher frequency of MMR-deficient SOCs was diagnosed at early stages compared with the patients in the MSS group (38.6% and 20.6%, respectively, p=0.022). The frequency of cases with PD-1 expression was significantly higher in the MSI-H group (76.2%) than in the MSS counterparts (58.8%, p=0.028). Patients in the MSI-H group had significantly longer DFS (25.6 months) and OS (not reached) than those in the MSS group (16 months and 48.9 months, p=0.039 and p=0.026, respectively). CONCLUSION: MSI-H SOCs were diagnosed at an earlier stage as compared to MMR proficient cases. The presence of PD-1 expression was significantly higher in cases presenting MMR deficiency compared with MMR-proficient cases. MSI status was significantly associated with DFS and OS. KEY WORDS: Serous ovarian cancer, Microsatellite instability, Mismatch repair deficiency.

Preoperative prediction of retroperitoneal lymph node involvement in clinical stage IB and IIA cervical cancer.

Objective: Lymph node metastasis (LNM) is the most important factor affecting survival in early-stage cervical cancer (CC). International Federation of Gynecology and Obstetrics revised the staging of CC in 2018 and reported LNM as a staging criterion. We investigated the preoperatively assessable risk factors associated with LNM in surgically treated stage IB1-IIA2 CC patients. Materials and Methods: This was a retrospective cohort study of women who underwent radical hysterectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy for CC stage IB1-IIA2 from 2004 to 2019. All patients included in this study were examined with speculum inspection, parametrial assessment by rectovaginal palpation under general anesthesia, transvaginal ultrasonography, magnetic resonance imaging (MRI), and chest radiography. Clinical staging was done according to the preoperative findings. MRI was used to measure tumor and lymph node dimensions. Results: Out of the 149 women included in the study, 29 (19.4%) had LNM. Univariate analysis revealed that larger tumor size (≥30 mm), lymphovascular space invasion (LVSI) detected with diagnostic biopsy, parametrial involvement, and deep stromal invasion status were significantly different between the group with LNM and the group without LNM. In multivariate analysis, specific preoperative risk factors such as MRI based tumor diameter ≥30 mm and LVSI (+) on the diagnostic biopsy were found to be independent risk factors for LNM in the multivariate analysis. Conclusion: The rate of LNM is high in patients with CC with a tumor size ≥30 mm and preoperative biopsy LVSI status even if they are clinically in early stages. Surgeons can take this into account while deciding between primary surgery and chemoradiotherapy in the treatment of CC.

High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective: The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis. Materials and Methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher's Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1. Results: Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS). Conclusion: Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.

Can maternal abdominal fat thickness predict antenatal insulin therapy in patients with gestational diabetes mellitus?

PURPOSE: This study aimed to investigate the effectiveness of abdominal subcutaneous fat thickness (ASFT) in predicting antenatal insulin therapy (AIT) in patients with gestational diabetes mellitus (GDM). METHODS: A prospective study was conducted on patients with regulated blood sugar levels (n = 50) and those with unregulated blood sugar (n = 50) although medical nutrition therapy (MNT) was initiated and then AIT was applied. Using receiver operator characteristic (ROC) curve analysis, appropriate ASFT cut-off point values were found for the prediction of cases that required AIT after MNT in GDM pregnancies. RESULTS: Patients with GDM who needed AIT had a significantly higher ASFT value compared to those with GDM who did not need AIT. The optimal ASFT cutoff was 21.7 mm in predicting cases that required AIT after MNT (sensitivity, specificity, negative, and positive predictive values were 68.0%, 64.0%, 65.8%, and 66.6%, respectively). The risk of AIT increased 3.77-fold in those with ASFT > 21.7 mm in GDM pregnancies (p = 0.001). CONCLUSION: The ASFT value was significantly higher in cases with GDM, with blood glucose levels not regulated despite MNT and AIT being then needed, compared to patients with blood glucose levels regulated by MNT, and who did not need AIT. Also, patients requiring AIT can be determined with moderate to high sensitivity and specificity using a cut-off value of ASFT > 21.7 mm. The ASFT > 21.7 mm cut-off point was seen to be more effective than BMI ≥ 30 kg/m2 in the determination of cases where AIT is required.

Comparison of the Quality of Life and Female Sexual Function Following Laparoscopic Pectopexy and Laparoscopic Sacrohysteropexy in Apical Prolapse Patients.

OBJECTIVES: We sought to compare the surgical outcomes, safety, effectiveness, and mid-term outcomes in patients who had undergone laparoscopic hysterosacropexy and laparoscopic pectopexy due to apical prolapse. MATERIALS AND METHODS: This prospective randomized study was conducted on a total of 62 women who underwent apical prolapse surgery (32 undergoing a pectopexy and 30 undergoing a sacrohysteropexy) between June 2015 and June 2017. Patients with symptomatic uterine or vaginal vault prolapse with stage 2 or worse were included in the sudy. Before and after the operation, we used the Pelvic Organ Prolapse Quantification System (POP-Q) and questionnaires, which are the Prolapse Quality of Life Questionnaire (P-QOL) and Female Sexual Function Index (FSFI), to evaluated cases. Baseline characteristics, perioperative and postoperative complications, and follow-up results at 12 months were also evaluated. RESULTS: All domains of POP-Q, P-QOL, and FSFI scores improved significantly after surgery both in pectopexy and sacrohysteropexy group. The postoperative complications of both procedures were similar except for constipation after surgery (3.2% in the pectopexy group and 20% in the hysterosacropexy group [P = 0.036]). CONCLUSION: Both sacrohysteropexy and pectopexy are effective surgical options for apical prolapse patients. The pectopexy is an acceptable alternative to laparoscopic sacrohysteropexy because of its less complexity and not reducing pelvic space for the rectum to exist. We suggest that the laparoscopic pectopexy may be widely used in clinical routine.

Maternal serum IL-22 concentrations are significantly upregulated in patients with preterm premature rupture of membranes.

OBJECTIVES: This study aimed to compare the serum IL-22 levels between preterm premature rupture of membranes (PPROM) patients and the control group with intact membranes. We also hypothesized whether serum IL-22 upregulation might contribute to defense against inflammatory responses and improve the pregnancy outcomes. MATERIAL AND METHODS: We performed this prospective case-control study between 24-34 weeks of pregnancy. We enrolled 40 singleton pregnant patients with PPROM and 40 healthy gestational age- and gravidity-matched patients without PPROM. The degree of association between variables and IL-22 were calculated by Spearman correlation coefficients where appropriate. Scatter plots were given for statistically significant correlations. ROC curve was constructed to illustrate the sensitivity and specificity performance characteristics of IL-22, and a cutoff value was estimated by using the index of Youden. RESULTS: Maternal serum IL-22 levels were significantly higher in PPROM patients (60.34 ± 139.81 pg/mL) compared to the participants in the control group (20.71 ± 4.36 pg/mL, p < 0.001). When we analyze the area under the ROC curve (AUC), the IL-22 value can be considered a statistically significant parameter for diagnosing PPROM. According to the Youden index, a 23.86 pg/mL cut-off value of IL-22 can be used to diagnosing PPROM with 72% sensitivity and 61.5% specificity. There was no positive correlation between serum IL-22 levels and maternal C-reactive protein (CRP) value, procalcitonin value, latency period, birth week, birth weight, and umbilical cord blood pH value. CONCLUSIONS: Maternal serum IL-22 levels were significantly higher in PPROM patients than healthy pregnant women with an intact membrane. We suggest that IL-22 might be a crucial biomarker of the inflammatory process in PPROM.

Management of gynecological cancers in the COVID-19 era: a survey from Turkey

Objective: This study aimed to investigate how gynecologic oncologists modified their patient management during Coronavirus disease-2019 (COVID-19) in Turkey. Material and Methods: An online survey was sent to gynecologic oncology specialists and fellows in Turkey. It included management questions about strategies for newly diagnosed or recurrent endometrial, cervical, ovarian and vulvar cancer during the pandemic. Participants were asked if treatment of these cancers can be delayed or not and, if yes, the duration of delay. Results: 32.9% of surgeons prescribed oral or intrauterine progesterone for early stage, low-grade endometrial cancer. Conversely, 65.7% and 45.7% of the most surgeons did not change their management for early stage high-grade and advanced stage endometrial cancers respectively, as they perform surgery. 58% and 67.1% of the surgeons continued to prefer standard surgical treatment for microinvasive and early stage cervical cancers, respectively. Radiotherapy was preferred administered with hypofractionated doses for locally advanced cervical cancer (57.1%). While 67.1% of surgeons operated early stage ovarian cancer patients, 50% administered neoadjuvant chemotherapy (NACT) to all advanced stage ovarian cancers and 50% administered more cycles of NACT in preference to interval debulking surgery. 93.7% of the surgeons responded that treatment should not be delayed beyond eight weeks. Conclusion: Most Turkish gynecologic oncologists modified their management of gynecologic cancers due to the COVID-19 pandemic. While chemotherapy was preferred for ovarian cancer, postponement of the surgery, with or without non-surgical options, was considered for early stage, low-grade endometrial cancer. Treatment of gynecologic cancers should be decided on a case by case basis, taking into account local COVID-19 infection rates and availability of health facilities. Prognosis is also an important consideration if delay is contemplated. Standard treatment and normal time-frames should be used if possible. If not, a postponement for a maximum of eight weeks or referral to another center were acceptable alternatives.

The effect of obesity on the onset of spontaneous labor and scheduled delivery rates in term pregnancies.

OBJECTIVE: To determine the effect of obesity on the onset of spontaneous labor, scheduled delivery rates and perinatal outcomes in term pregnancies. MATERIAL AND METHODS: 242 obese and 244 non-obese pregnant women ≥37 gestational weeks were compared in terms of the onset of spontaneous labor, scheduled delivery rates and perinatal outcomes. RESULTS: Obese pregnant women had statistically significantly lower onset of spontaneous labor and higher rates of scheduled delivery. No difference was determined in respect of the type of delivery, 1st and 5th minutes APGAR scores and the need for intensive care. Higher values of birth weight, large for gestational age, macrosomia, gestational diabetes mellitus and preeclampsia were determined in obese women. CONCLUSION: The onset of spontaneous labor rates in term obese pregnancies were lower and scheduled delivery rates were higher than in the non-obese pregnancies. However, more extensive studies are needed to better understand this relationship.

Is there an association between congenital nasolacrimal duct obstruction and cesarean delivery?

PURPOSE: The aim of this study was to research the relationship between types of birth and congenital nasolacrimal duct obstruction. METHOD: The study enrolled 665 infantile patients with prediagnosis of congenital nasolacrimal duct obstruction due to associated ophthalmic symptoms. Age, gender, family history, delivery type, and patient medical records were investigated. Patients were grouped and compared according to their birth type and whether it was the first birth. RESULTS: The number of the infants with and without congenital nasolacrimal duct obstruction was 227 (34.1%) and 438 (65.9%), respectively. Comparison of the congenital nasolacrimal duct obstruction and non-congenital nasolacrimal duct obstruction groups according to the first births showed that ratio of cesarean section was significantly higher in the congenital nasolacrimal duct obstruction group than the non- congenital nasolacrimal duct obstruction group (58.7% and 20.7%, respectively). Number with positive family history also was significantly higher in the congenital nasolacrimal duct obstruction group. CONCLUSION: Cesarean section in first birth and positive family history of congenital nasolacrimal duct obstruction appear to be important risk factors in the etiopathogenesis of congenital nasolacrimal duct obstruction.

Comparison of survival outcomes in optimally and maximally cytoreduced stage IIIC ovarian high-grade serous carcinoma: Women with only peritoneal tumor burden versus women with both peritoneal and lymphogenous dissemination.

AIM: The aim of this study was to analyze the survival outcomes of stage IIIC ovarian high-grade serous carcinoma (HGSC) patients with both peritoneal and lymphatic dissemination (IP+/RP+) who had undergone maximal or optimal cytoreduction followed by intravenous carboplatin/paclitaxel chemotherapy compared to those women with stage IIIC ovarian HGSC with only peritoneal involvement (IP+/RP-) who were treated similarly. METHODS: We performed a retrospective, multicenter study with the participation of five gynecological cancer centers. First, the stage IIIC ovarian HGSC patients were classified into optimally or maximally debulked cohorts. Then, in each cohort, the patients were divided into two groups; the IP+/RP- group included those women with transcoelomic spreading outside the pelvis with no nodal disease, and the IP+/RP+ group included those patients with transcoelomic dissemination outside the pelvis in addition to a positive nodal status. The survival outcomes were compared between the two groups in each cohort. RESULTS: A total of 405 ovarian HGSC patients were analyzed. In the optimally debulked cohort (n = 257), the progression-free survival (PFS) and overall survival (OS) medians for the IP+/RP- group (n = 69) were 24 and 57 months, respectively, compared to 21 and 58 months, respectively, for the IP+/RP+ group (n = 188) (P = 0.78 and P = 0.40, respectively). In the maximally debulked cohort (n = 148), the PFS and OS medians for the IP+/RP- group (n = 55) were 35 and 63 months, respectively, compared to 25 and 51 months, respectively, for the IP+/RP+ group (n = 93) (P = 0.49 and P = 0.31, respectively). CONCLUSION: Our findings indicated no survival differences between the IP+/RP- and the IP+/RP+ groups.

Maternal abdominal subcutaneous fat thickness as a simple predictor for gestational diabetes mellitus.

Background To date, only a limited number of studies have evaluated the importance of abdominal subcutaneous fat thickness (ASFT) on gestational diabetes mellitus (GDM) screening. The aim of this study was to investigate the effectiveness of ASFT measurement during routine obstetric ultrasound performed between 24 and 28 weeks of gestation in predicting cases with GDM. Methods This prospective comparative study was conducted on 50 cases with GDM and 50 cases without GDM in the GDM screening program at 24-28 gestational weeks between January 2018 and May 2018. The most accurate ASFT cut-off point values were determined for the prediction of cases with GDM by performing receiver operator characteristic (ROC) curve analysis. Results The ASFT was higher in those with GDM compared to those without GDM (P < 0.05). For an ASFT cut-off point value of 18.1 mm for the prediction of cases with GDM, the sensitivity, specificity, negative and positive predictive values were 72.0%, 60.0%, 64.2% and 68.1%, respectively. The risk of GDM increased 3.86-fold in those with ASFT level >18.1 mm (P = 0.001). Conclusion The ASFT value measured by routine obstetric ultrasound performed at 24-28 weeks of gestation was found to be significantly higher in patients with GDM in comparison to those without GDM. However, further multi-centered and comprehensive prospective studies are required to better demonstrate this relationship.

An investigation of the effect of placental growth factor on intrapartum fetal compromise prediction in terminduced high risk pregnancies.

OBJECTIVES: To date, there is no available test to predict the risk of intrapartum fetal compromise (IFC) during labor, either starting spontaneously or induced due to obstetrics indications. The aim of this study was to examine the effectiveness of placental growth factor (PIGF) in identifying cases that develop intrapartum fetal compromise (IFC) in term high-risk pregnancies induced for labor. MATERIAL AND METHODS: This prospective cross-sectional study was conducted on 40 IFC+ cases and 40 IFC- cases with high-risk term pregnancy and labor induction started in the Health Sciences University Gazi Yasargil Training and Research Hospital, between January 2018 and April 2018. Comparisons were made between the groups in respect of placental growth factor (PIGF) levels, and obstetric and neonatal outcomes. RESULTS: The PIGF level was found to be statistically significantly lower in the IFC+ cases compared to the IFC- cases. For a PIGF cutoff value of 32 pg/mL for the prediction of IFC+ cases, sensitivity was 74.4%, specificity 73.2%, NPV 75% and PPV 72.5%, with a statistically significant difference determined between the groups. The IFC+ development risk increased 7.91-fold in patients with PIGF ≤ 32 pg/mL. CONCLUSIONS: The PIGF levels in cases of IFC+ high risk pregnancies were found to be statistically significantly lower than those of IFC- cases. However, further, large-scale randomized controlled research is necessary to demonstrate this relationship better.

A comparative study of conventional and liquid-based cervical cytology.

OBJECTIVES: The aim of our study is the comparison of the results of conventional smear (CC) technique and liquidbased cytology (LBC) technique used as cervical cancer screening methods. MATERIAL AND METHODS: The results of 47954 patients submitted to smear screening in our gynecology clinic between January 2008 and December 2014 have been studied. The smear results have been divided into two groups CC and LBC according to the technique used. RESULTS: When considering the distribution within CC group, the results were as follows: intraepithelial cell abnormalities 2,0% (n=619), insufficient sample for analysis 2,1% (n=660), Atypical squamous cells of undetermined significance (ASC-US) 1.8% (n=554), Low grade squamous intraepithelial lesion (LGSIL) 0.1% (n=35), High grade squamous intraepithelial lesion (HGSIL) 0.1% (n=16), Atypical squamous cells - cannot exclude HGSIL (ASC-H) 0.029% (n=9), Atypical glandular cells- not other wise specified (AGC-NOS) 0.012% (n=4), squamous carcinoma 0.003% (n=1). When considering the distribution in LBC group, the results were as follows: intraepithelial cell abnormalities2.1% (n=357), insufficient sample for analysis 0.9% (n=144), ASC-US 1.8% (n=296), LGSIL 0.2% (n=38), HGSIL 0.1% (n=8), ASC-H 0.1% (n=10), AGC-NOS 0.017% (n=3), squamous carcinoma 0.011% (n=2). CONCLUSIONS: Although the rates of epithelial cell abnormalities are similar for both tests, LSIL results are more frequently observed in LBC technique. In LBC technique, the number of insufficient sample for analysis is quite low compared to CC group and thus constitutes an advantage.