Prediction of final pathology depending on preoperative myometrial invasion and grade assessment in low-risk endometrial cancer patients: A Korean Gynecologic Oncology Group ancillary study.

OBJECTIVES: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST. METHODS/MATERIALS: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed. RESULTS: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4). CONCLUSIONS: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction.

Menopausal status induces vaginal dysbiosis in women with human papillomavirus infection.

In this study, we examined the difference in the vaginal microbiota of women infected with human papillomavirus (HPV), according to menopausal status. A total of 75 cervicovaginal swab samples from 38 pre- and 37 postmenopausal women with HPV infection were obtained from the Korean HPV cohort. Vaginal microbiota analysis, including microbial diversity and specific bacterial abundances, was performed using 16S rRNA gene sequencing. The mean age of the pre- and postmenopausal women were 29.5 and 55.8 years, respectively (p < 0.0001). Lactobacillus spp. were predominant in both groups; however, a marked decrease was observed in postmenopausal women compared to premenopausal women (44.3% vs. 74.2%). Various anaerobic bacteria also showed a relatively high abundance in the postmenopausal group; Atopobium vagina and Gardnerella vaginalis significantly increased in postmenopausal women. Interestingly, no significant differences in bacterial richness were observed between the two groups. However, significant differences in beta-diversity were observed using the Bray-Curtis (p = 0.001), Generalized UniFrac (p = 0.002), Jensen-Shannon (p = 0.001), and UniFrac algorithms (p = 0.002). Theres results indicate that postmenopausal women with HPV infection exhibited a higher degree of vaginal dysbiosis than premenopausal women. Further, HPV-infected postmenopausal women had increased vaginal microbial diversity, characterized by an increase in anaerobic bacteria and concomitant depletion of Lactobacillus spp.

Comparison of survival outcome of open, total laparoscopic, and laparoscopy-assisted radical vaginal hysterectomy for stage IB2 cervical cancer patients: A multicenter retrospective study.

The aim of this study was to compare survival outcomes of 3 different radical hysterectomy (RH) types, namely total abdominal radical hysterectomy (TARH), total laparoscopic radical hysterectomy (TLRH), and laparoscopy-assisted radical vaginal hysterectomy (LARVH), in patients with FIGO stage IB2 cervical cancer. We retrospectively identified a cohort of patients who underwent RH for cervical cancer between 2010 and 2017. Patients with stage IB2 cervical cancer were included and were classified into TARH, TLRH, and LARVH treatment groups. Survival outcomes were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to estimate the independent association of RH technique with outcome. 194 patients were included in this study: 79 patients in the TARH group, 55 in the TLRH group, and 60 in the LARVH group. No significant differences were found in clinicopathological characteristics between the 3 RH groups. On comparing survival outcomes with TARH, both TLRH and LARVH showed no significant difference in terms of 5-year overall survival (TARH vs TLRH, P = .121 and TARH vs LARVH, P = .436). Conversely, compared to the TARH group, 5-year progression-free survival (PFS) was significantly worse in the TLRH group (P = .034) but not in the LARVH group (P = .288). Multivariate analysis showed that TLRH surgical approach (hazard ratio, 3.232; 95% confidence interval, 1.238-8.438; P = .017) was an independent prognostic factor for PFS in patients with IB2 cervical cancer. Our study suggests that in patients with FIGO stage IB2 cervical cancer, among the minimally invasive RH approaches, TLRH and LARVH, only TLRH approach was associated with worse PFS when compared with the TARH approach.

Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial).

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

Risk Factors and Pregnancy Outcomes of Antepartum Hemorrhage in Women with Placenta Previa.

Placenta previa (PP) is one such complication related to several adverse pregnancy outcomes. Adverse outcomes are likely greater if PP coexists with antepartum hemorrhage (APH). This study aims to evaluate the risk factors and pregnancy outcomes of APH in women with PP. This retrospective case-control study included 125 singleton pregnancies with PP who delivered between 2017 and 2019. Women with PP were divided into two groups: PP without APH (n = 59) and PP with APH (n = 66). We investigated the risk factors associated with APH and compared the differences between both groups in placental histopathology lesions due to APH and the resulting maternal and neonatal outcomes. Women with APH had more frequent antepartum uterine contractions (33.3% vs. 10.2%, P = .002) and short cervical length (< 2.5 cm) at admission (53.0% vs. 27.1%, P = .003). The placentas from the APH group had lower weight (442.9 ± 110.1 vs. 488.3 ± 117.7 g, P = .03) in the gross findings, and a higher rate of villous agglutination lesions (42.4% vs. 22.0%, P = .01) in the histopathologic findings. Women with APH in PP had higher rates of composite adverse pregnancy outcomes (83.3% vs. 49.2%, P = .0001). Neonates born to women with APH in PP had worse neonatal outcomes (59.1% vs. 23.9%, P = .0001). Preterm uterine contractions and short cervical length were the most significant risk factors for APH in PP.

Frequency of serous tubal intraepithelial carcinoma (STIC) in patients with high grade serous ovarian cancer.

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is a known precursor of high-grade serous ovarian cancer (HGSOC). This study aimed to evaluate the proportion of STIC in patients with HGSOC and analyze the STIC-related prognosis in patients with HGSOC. MATERIALS AND METHODS: All pathology reports at our institution that included bilateral salpingectomies of patients with HGSOC from January 2013 to December 2018 were reviewed by two experienced pathologists. The specimens from the ovaries and the salpinx including fimbria were examined. We analyzed the correlation between STIC and HGSOC and compared the clinical characteristics and STIC-related prognostic outcomes in patients with HGSOC. RESULTS: Eleven of the 76 cases were STIC. BRCA mutations were found in 16.9% of patients with HGSOC. STIC was observed in 30.0% of patients with BRCA mutations and in 14.3% of patients without BRCA mutations. The incidence of STIC in patients with BRCA mutations was approximately twice that in patients without BRCA mutations; however, the difference was not statistically significant (P = 0.231). Further, the 5-year survival rate of patients without STIC appeared to be high; nevertheless, the difference was not statistically significant (59.7% vs. 47.4%, P = 0.633). Moreover, there was no significant difference in disease-free survival rate according to STIC (36.4% vs. 33.1%, P = 0.956). CONCLUSION: STIC was identified in patients with HGSOC, and STIC incidence was prominent in HGSOC related to BRCA mutation. Although low frequency, STIC was detected in patients without BRCA mutation. Therefore, prophylactic salpingectomy may be useful for prevention of HGSOC.

VSIG4-expressing tumor-associated macrophages impair anti-tumor immunity.

VSIG4, a newly identified co-inhibitory molecule belonging to the B7-related family, is exclusively expressed on tissue-resident macrophages and is involved in the suppression of T cell proliferation and cytokine production. We sought to characterize the role of VSIG4 in anti-tumor immunity in the tumor microenvironment, focusing on VSIG4-expressing tumor-associated macrophages (TAMs). We found that VSIG4-expressing TAMs negatively regulated antigen-specific T cell proliferation and cytokine production through direct inhibition via cell cycle arrest, but not apoptosis, as well as through their arginase 1 activity. Furthermore, VSIG4-expressing TAMs suppress tumor-specific CD8+ T cell cytotoxicity. Therefore, our results suggest that VSIG4-expressing TAMs could be a negative cellular regulator of anti-tumor immunity in the tumor microenvironment.

Coexpression of lymphocyte-activation gene 3 and programmed death ligand-1 in tumor infiltrating immune cells predicts worse outcome in renal cell carcinoma.

OBJECTIVES: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1). METHODS: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers. RESULTS: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS. CONCLUSION: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial.

BACKGROUND: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. METHODS: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734665.

Effects of cisplatin on mitochondrial function and autophagy-related proteins in skeletal muscle of rats.

Cisplatin is widely known as an anti-cancer drug. However, the effects of cisplatin on mitochondrial function and autophagyrelated proteins levels in the skeletal muscle are unclear. The purpose of this study was to investigate the effect of different doses of cisplatin on mitochondrial function and autophagy-related protein levels in the skeletal muscle of rats. Eight-weekold male Wistar rats (n = 24) were assigned to one of three groups; the first group was administered a saline placebo (CON, n = 10), and the second and third groups were given 0.1 mg/kg body weight (BW) (n = 6), and 0.5 mg/kg BW (n = 8) of cisplatin, respectively. The group that had been administered 0.5 mg cisplatin exhibited a reduced BW, skeletal muscle tissue weight, and mitochondrial function and upregulated levels of autophagy-related proteins, including LC3II, Beclin 1, and BNIP3. Moreover, this group had a high LC3 II/I ratio in the skeletal muscle; i.e., the administration of a high dose of cisplatin decreased the muscle mass and mitochondrial function and increased the levels of autophagy-related proteins. These results, thus, suggest that reducing mitochondrial dysfunction and autophagy pathways may be important for preventing skeletal muscle atrophy following cisplatin administration. [BMB Reports 2021; 54(11): 575-580].

Prognostic factors of oncologic outcomes after fertility-preservative management with progestin in early-stage of endometrial cancer.

BACKGROUND: The aim of this study was to evaluate efficacy of various fertility-preservative treatments with progestin and analyze prognostic factors in Stage 1A of endometrial cancer. MATERIALS AND METHODS: This retrospective study involved four Korean university hospitals. Data were collected from 43 women who were under the age of 40 with presumed stage IA endometrial cancer determined by magnetic resonance imaging and treated from January 2014 to December 2017. All of the patients were administered hormonal therapy for fertility preservation. Twenty-five patients received oral progestin with a levonorgestrel-releasing intrauterine system (LNG-IUS) for 6-24 months, and 18 patients received high-dose oral progestin for the same period of time. Oncologic outcomes were evaluated. Prognostic factors for pathologic response to progestin were identified by logistic regression analysis. RESULTS: Complete response (CR) was achieved by 72.1% of patients (31/43), and the average time to CR was 4.2 (Stable disease [SD] 3.4) months (range, 3-9 months). Partial response was achieved by 7.0% of patients (3/43), SD by 9.3% (4/43), and progressive disease by 11.6% (5/43). Of the CR patients, 41.9% (13/31) achieved pregnancy with the median follow-up period of 12.5 (SD 7.6) months (range: 3-50 months). No irreversible toxicity or therapy-associated death occurred. Multivariate analysis showed that high endometrial thickness ratio of pre- and posttreatment measured at 2 months from the treatment initiation (≥0.55, Odds ratio [OR]: 19.018; 95% confidence intervals (CI): 1.854-195.078; P = 0.013) and oral progestin without LNG-IUS (OR: 13.483; 95% CI: 1.356-134.069; P = 0.026) might be related with unfavorable prognostic factors for CR. CONCLUSION: This study shows that progestin-based fertility-preservative treatment might be a feasible option for stage 1A endometrial cancer. It also identifies that low endometrial thickness ratio and oral progestin with LNG-IUS combination therapy might be related with favorable response to hormonal treatment.

Preoperative Blood Inflammatory Markers for the Differentiation of Uterine Leiomyosarcoma from Leiomyoma.

PURPOSE: Preoperative diagnosis of uterine leiomyosarcoma (LMS) is challenging because the disease can mimic benign leiomyoma (LM). The objective of the present study was to investigate the role of preoperative clinical characteristics and hematologic parameters to differentiate uterine LMS and LM. METHODS: Preoperative clinical and laboratory variables were reviewed retrospectively in patients with LMS or LM, and the significances of intergroup differences were assessed. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values for each variable. Logistic regression analysis was applied to identify variables predicting the presence of LMS. RESULTS: The preoperative clinical and laboratory variables of 336 patients with uterine tumor were analyzed. Seventy-nine patients had LMS and 257 had LM. A significant difference was observed between LMS and LM in terms of the median value of age at diagnosis, menopausal status, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP), lactate dehydrogenase (LDH), and neutrophil-to-lymphocyte ratio (NLR) (all P < 0.001). Multivariate analyses showed that menopausal status (odds ratio [OR] = 3.40, P= 0.002), WBC count (OR = 2.09, P = 0.012), ANC (OR = 3.17, P < 0.001), CRP (OR = 21.74, P < 0.001), LDH (OR = 10.77, P < 0.001), and NLR (OR = 2.58, P = 0.001) predicted the presence of LMS. CONCLUSION: Our results suggest that in older or postmenopausal patients, high WBC count, ANC, CRP, LDH, and NLR could be useful biomarkers for the differentiation of LMS and LM, which indicate that serum markers might be useful, cost-effective, and broadly available diagnostic markers for uterine LMS.

Diagnostic Performance of F-18 FDG PET/CT Compared with CA125, HE4, and ROMA for Epithelial Ovarian Cancer.

OBJECTIVE: This study aimed to examine the diagnostic performance of F-18 fluorodeoxyglucose positron emission tomography with computed tomography (F-18 FDG PET/CT) compared with cancer antigen 125 (CA125), human epididymis protein 4 (HE4), and risk of ovarian malignancy algorithm (ROMA) score to distinguish epithelial ovarian cancer from benign tumors. METHODS: A total of 46 patients with pelvic masses, who underwent F-18 FDG PET/CT, CA125, and HE4 before surgery between January 2015 and December 2018, were included in this retrospective study. The diagnostic performance of CA125, HE4, ROMA score, and maximum standardized uptake value (SUVmax) to differentiate epithelial ovarian cancer from benign pelvic tumors was examined by receiver operating characteristic curve analysis. RESULTS: Among the 46 patients, 28 were cases of ovarian cancers and 18 were of benign. The mean values of CA125, HE4, ROMA score, and SUVmax were significantly higher in the ovarian cancer group than the benign group. In early cancer stages (stages I and II), Area under the curve for SUVmax was significantly higher than CA125 and ROMA score (0.778 for CA125, 0.753 for HE4, 0.682 for ROMA score, and 0.922 for SUVmax). CONCLUSION: SUVmax using F-18 FDG PET/CT showed a high diagnostic accuracy for differentiating epithelial ovarian cancer from benign pelvic tumors, including early stage ovarian cancer. F-18 FDG PET/CT can be a useful modality for the assessment of pelvic mass.
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Expression of VISTA on tumor-infiltrating immune cells correlated with short intravesical recurrence in non-muscle-invasive bladder cancer.

V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint molecule expressed in hematopoietic cells, granulocytes, macrophages, and monocytes. However, few studies to date have investigated VISTA expression, especially its clinical utility, in bladder cancer. The present retrospective study aimed to examine VISTA, programmed death ligand-1 (PD-L1), and CD45 expression by immunohistochemical and immunofluorescence staining of archived pathological tissue samples from 159 patients with primary bladder cancer. The correlation between VISTA expression in immune cells (ICs) and clinicopathologic variables including PD-L1 expression in ICs was examined. Briefly, the rates of VISTA-positive ICs and VISTA-positive tumor cells were 67.9% (108/159) and 30.8% (49/159), respectively. The VISTA expression in ICs of patients with bladder cancer, including those with non-muscle-invasive bladder cancer (NMIBC), was positively correlated with tumor stage, grade, size, and multiplicity. The VISTA expression in ICs was stronger in bladder cancer cases with PD-L1-positive ICs than in those with PD-L1-negative ICs (p < 0.001). The mean intravesical recurrence-free survival was shorter in NMIBC cases with VISTA-positive ICs than in those with VISTA-negative ICs (34.0 vs 39.9 months, p = 0.03, log-rank test). In this first study to investigate VISTA expression in bladder cancer, these results implicate VISTA as a potential immunotherapeutic target and immunologic biomarker in bladder cancer.

The clinical significance of HERV-H LTR -associating 2 expression in cervical adenocarcinoma.

ABSTRACT: HERV-H LTR -associating 2 (HHLA2) is a recently discovered member of the B7-family of immune checkpoint molecules that is overexpressed in several types of cancer. The aim of the present study was to investigate the expression of HHLA2 in cervical adenocarcinoma (AC) and the relationship between its expression and clinicopathological factors to assess its use as a potential marker for AC prognosis.This study included 76 patients diagnosed with cervical AC. Their resected specimens were obtained and a tissue microarray was constructed. Expression of HHLA2 was detected by the immunohistochemistry. Based on the follow-up data, correlation of HHLA2 expression and clinicopathological features, including overall survival (OS) and disease-free survival, was evaluated. Furthermore, we investigated the correlation between the expression of HHLA2 and programmed death ligand 1 (PD-L1).A total of 76 cases of invasive cervical AC were evaluated. High HHLA2 expression was detected in 62 cases (81.6%) and low HHLA2 expression was presented in 14 cases (18.4%). HHLA2 expression showed a significant negative correlation with lymph node metastasis (P = .011). Disease free survival was 75.0% and 49.0% in high-expression and the low expression group, respectively (P = .057). Although there was no statistical significance, an improved OS was observed in the high expression group (83.1% vs 64.9%, P = .479). Further, the expression of HHLA2 and PD-L1 correlated positively (P = .005). Thus, an improved OS was observed in the PD-L1 expression group (90.7% vs 66.2%, P = .037).High expression of HHLA2 is related to tumor progression and prognosis in patients with cervical AC. Therefore, HHLA2 may be a potential biomarker for predicting prognosis of cervical AC.

Neonatal outcomes between discordant monochorionic and dichorionic twins.

OBJECTIVES: This study aimed to compare obstetrical complications and neonatal outcomes between monochorionic and dichorionic discordant twin pregnancies. STUDY DESIGN: We enrolled 296 patients with twin pregnancy who delivered at Busan Paik Hospital between January 2014 and December 2017. The prevalence of obstetrical complications, neonatal mortality between monochorionic and dichorionic twins was compared. We also investigated whether there is a difference in neonatal outcome and neonatal morbidity between monochorionic discordant twins without monochorionic-specific complications and dichorionic discordant twins. RESULTS: The risk of fetal death in utero (13.2 versus 5.2%, p = .025) and inter twin birth weight discordance (35.1 versus 20.8%, p = .031) is increased in monochorionic twins than in dichorionic twins. However, no difference was noted in obstetrical complication and neonatal mortality and morbidity between two groups. Among twin pregnancies with intertwin birth weight discordance, after excluding fetal death in utero and monochorionic specific complication, there was no difference in obstetrical complication and neonatal mortality and morbidity according to chorionicity. There was no difference in neonatal morbidity between monochorionic twins and dichorionic twins when comparing larger neonates and smaller neonates of each group. CONCLUSIONS: Risk of birth weight discordance is higher in monochorionic twin but no significant difference was observed in maternal outcomes, neonatal mortality and morbidity between noncomplicated monochorionic and dichorionic discordant twins.

Placental Pathologic Changes Associated with Fetal Growth Restriction and Consequent Neonatal Outcomes.

OBJECTIVE: To evaluate the pathological changes of the placenta to determine the mechanism underlying placenta-derived fetal growth restriction (FGR) and investigate its influence on neonatal outcomes. Study design: This retrospective case-control study included 120 singleton pregnancies with FGR as well as 120 gestational age-matched controls. We compared the placental pathological findings and neonatal outcomes according to the presence of placental malperfusion. Results: The FGR group demonstrated lower placental weight (350.8 ± 118.8 vs. 436.1 ± 109.7g, P < .0001), smaller chorionic plate area (157.7 ± 48.0 vs. 201.5 ± 53.4 cm2, P < .0001), and higher rate of villous change lesions (84.2% vs. 52.5%, P < .0001) than the control group. FGR neonates with placental malperfusion had a higher rate of adverse neonatal outcomes (87.1% vs. 63.2%, P = .0175). Conclusion: Small placentas and placental malperfusion reflected in villous changes are associated with FGR. FGR neonates with placental malperfusion are more susceptible to adverse neonatal outcomes.

Immunoregulatory protein V-set and immunoglobulin domain-containing 4 is overexpressed in patients with endometriosis.

AIM: V-set and immunoglobulin domain-containing 4 (VSIG4) is a potent negative regulator of T-cell responses and is suggested to regulate antitumor immunity. This study investigates whether VSIG4 is significantly expressed in endometriosis patients and the association between VSIG4 levels and serum cancer antigen (CA)-125 levels, VSIG4 levels and endometriosis severity. METHODS: Tumor tissues and peripheral blood samples were obtained during surgery from 42 endometriotic cyst and 21 nonendometriotic tumor patients. The levels of VSIG4 mRNA, VSIG4 protein expression in tumor tissue and serum soluble VSIG4 concentration were compared between the two groups. After dividing the cohort using the optimized cut-off values obtained by receiver operating characteristic curve analysis, we examined the association between VSIG4 levels and serum CA-125 levels, VSIG4 levels and the factors indicating endometriosis severity. RESULTS: The expressions of VSIG4 mRNA, VSIG4 protein and serum VSIG4 concentration were significantly increased in the endometriotic cyst group compared with the control group (P = 0.001, 0.002 and 0.049, respectively). The optimized VSIG4 cut-off values for endometriosis prediction were 0.71, 0.32 and 144.37 pg/mL, respectively. After cohort division using these values, high VSIG4 levels group showed significantly elevated CA-125 compared with low VSIG4 level group (P = 0.010, 0.043 and 0.039, respectively). There was no association between VSIG4 levels and the factors indicating endometriosis severity. CONCLUSION: The expression of VSIG4 in endometriosis patients is increased compared with nonendometriotic tumor patients, and higher VSIG4 levels are significantly associated with higher serum CA-125 levels. VSIG4 may be importantly involved in the immunological alteration of endometriosis.

The association between expression of p53 and aggressiveness of serous adenocarcinoma of the uterine cervix.

BACKGROUND: Serous adenocarcinoma of the uterine cervix is an extremely rare variant of cervical adenocarcinoma. This study aimed to evaluate the clinicopathological and molecular features and outcomes of serous adenocarcinoma of the uterine cervix (SACC). MATERIALS AND METHODS: This was a retrospective study conducted based on the clinical and pathological data of seven patients diagnosed with SACC after hysterectomy, who were evaluated at the gynecologic oncologic centers between 2010 and 2019. RESULTS: Five cases were diagnosed at Stage IB and two at Stage IV. All patients underwent radical hysterectomy with bilateral salpingo-oophorectomy and subsequently received postoperative radiotherapy or chemotherapy. One patient showed persistent disease, and two patients suffered recurrence. Immunohistochemical study showed that three (43%) of the seven patients were positive for p53, and among these three patients, two with diffuse strong p53 expression experienced an aggressive course with recurrences at pelvic lymph nodes, lung, and brain. CONCLUSION: High p53 expression and advanced stage may be associated with poorer clinical outcomes in SACC, which suggest that immunohistochemistry may contribute to the prediction of prognosis.

Antibiotic prophylaxis for gynecologic cancer surgery.

OBJECTIVES: The use of prophylactic antibiotics in elective gynecologic cancer surgery is essential. We aimed to establish the optimal duration of antibiotic administration to reduce the overuse of antibiotics in gynecologic cancer surgery. MATERIALS AND METHODS: We conducted a retrospective study based on the descriptive and statistical analysis of the clinical records of patients who underwent a radical hysterectomy or staging operation for gynecologic cancer between January 2014 and October 2015 at Busan Paik Hospital. Postoperative outcomes, such as surgical site infection (SSI), urinary tract infection (UTI), length of hospital stay, duration of urinary catheterization, and duration of surgical drainage, were compared between the antibiotic prophylaxis for 1-day and greater than 1-day groups. RESULTS: A total of 139 patients were included in the study. There were 79 patients in the 1-day group (56.8%) and 60 patients in the >1-day (43.2%) group. The two groups were similar in terms of demographics, American Society of Anesthesiologists score, stage, surgical approach, and type of operation. Blood loss was smaller in the 1-day group than in the >1-day group (582.2 ± 278.3 cc vs. 795.9 ± 617.9 cc, P = 0.007). The average length of hospital stay was shorter in the 1-day group than in the >1-day group (10.8 ± 2.7 days vs. 11.8 ± 2.8 days, P = 0.039). The rate of SSI and UTI was not significantly different between the 1-day and >1-day groups (6.3% vs. 8.2% and 11.4% vs. 6.7%, respectively [P = 0.903 and P = 0.393]). CONCLUSION: One-day first generation cephalosporin administration is appropriate for preventing post-surgical complications such as wound infections, UTIs, and vaginal cuff cellulitis in gynecologic cancer surgery.