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PurposeThis study was to investigate the frequency of mismatch repair deficiency/high microsatellite instability (MMRd/MSI-H) in gynecologic malignancies and the efficacy of immune checkpoint inhibitors (ICIs) in patients with recurrent gynecologic cancers according to MMR/MSI status.Materials and MethodsWe conducted a multi-center retrospective review on the patients who were diagnosed with gynecologic cancers between 2015 and 2020. Their clinicopathologic information, results of immunohistochemistry staining for MLH1/MSH2/MSH6/PMS2 and MSI analysis, tumor response to treatment with ICIs were investigated.ResultsAmong 1,093 patients included in the analysis, MMRd/MSI-H was most frequent in endometrial/uterine cancers (34.8%, 164/471), followed by ovarian, tubal, and peritoneal cancers (12.8%, 54/422) and cervical cancer (11.3%, 21/186). When assessed by histology without regard for cancer types, the frequency of MMRd/MSI-H was 11.0% (38/345) in high-grade serous adenocarcinoma, 38.6% (117/303) in endometrioid adenocarcinoma, and 30.2% (16/53) in carcinosarcoma. A total of 114 patients were treated with ICIs at least once. The objective response rate (ORR) was 21.6% (8/37) in cervical cancer, 4.7% (2/43) in ovarian cancer, and 25.8% (8/31) in endometrial/uterine cancers. Univariate regression analysis identified MMRd/MSI-H as the only significant factor associated with the ORR (28.9% [11/38] vs. 11.8% [9/76]; odds ratio, 3.033; 95% confidence interval, 1.129–8.144; p=0.028).ConclusionThe frequency of MMRd/MSI-H is moderate to high in gynecologic cancers in the Korean population. MMRd/MSI-H could be effective predictive biomarkers in gynecologic cancers of any type.

A genetic etiology of male infertility is identified in fewer than 25% of infertile men, while 30% of infertile men lack a clear etiology, resulting in a diagnosis of idiopathic male infertility. Advances in reproductive genetics have provided insights into the mechanisms of male infertility, and a characterization of the genetic basis of male infertility may have broad implications for understanding the causes of infertility and determining the prognosis, optimal treatment, and management of couples. In a substantial proportion of patients with azoospermia, known genetic factors contribute to male infertility. Additionally, the number of identified genetic anomalies in other etiologies of male infertility is growing through advances in whole-genome amplification and next-generation sequencing. In this review, we present an up-to-date overview of the indications for appropriate genetic tests, summarize the characteristics of chromosomal and genetic diseases, and discuss the treatment of couples with genetic infertility by microdissection-testicular sperm extraction, personalized hormone therapy, and in vitro fertilization with pre-implantation genetic testing.

Purpose While the risk of lower limb lymphedema (LLE) after radical surgery for gynecologic malignancies is multifactorial, the limited assessment of lymph nodes (LNs), such as sentinel LN biopsy, has been incorporated into a standard procedure. We assessed the relationship between the number of LNs retrieved from the hemipelvis and the incidence of ipsilateral LLE (iLLE). Methods This retrospective study included 103 women with gynecologic cancer who had LNs removed with minimally invasive surgery between January 2014 and December 2018. For early detection of LLE, the patients were followed up by a lymphedema specialist who complied with the International Society of Lymphedema criteria. Potential risk factors for LLE were collected, and the risk factors were further investigated according to the number of LNs removed in a side-specific manner. Results LLE was diagnosed in 32 (31.1%) patients, and most of them were diagnosed with unilateral (n = 22) LLE rather than bilateral (n = 10). The number of pelvic LNs removed (p = 0.018), no lymphatic mapping (p = 0.034), and radiation (p = 0.020) were associated with the development of one or both LLEs. A side-specific analysis revealed that the incidence of iLLE increased significantly when four or more LNs were removed from the hemipelvis compared with three or fewer LNs (22.9% vs. 8.3%, p = 0.048). Conclusions The number of pelvic LNs retrieved was associated with the incidence of LLE in patients with early gynecologic cancer. We identified the cutoff number per hemipelvis through side-specific analysis that could minimize the risk of iLLE. Further studies are needed to validate our results.

PurposeIn this study, we investigated the frequencies of mutations in DNA damage repair genes including BRCA1, BRCA2, homologous recombination genes and TP53 gene in ovarian high-grade serous carcinoma, alongside those of germline and somatic BRCA mutations, with the aim of improving the identification of patients suitable for treatment with poly(ADP-ribose) polymerase inhibitors.Materials and MethodsTissue samples from 77 Korean patients with ovarian high-grade serous carcinoma were subjected to next-generation sequencing. Pathogenic alterations of 38 DNA damage repair genes and TP53 gene and their relationships with patient survival were examined. Additionally, we analyzed BRCA germline variants in blood samples from 47 of the patients for comparison.ResultsBRCA1, BRCA2, and TP53 mutations were detected in 28.6%, 5.2%, and 80.5% of the 77 patients, respectively. Alterations in RAD50, ATR, MSH6, MSH2, and FANCA were also identified. At least one mutation in a DNA damage repair gene was detected in 40.3% of patients (31/77). Germline and somatic BRCA mutations were found in 20 of 47 patients (42.6%), and four patients had only somatic mutations without germline mutations (8.5%, 4/47). Patients with DNA damage repair gene alterations with or without TP53mutation, exhibited better disease-free survival than those with TP53 mutation alone.ConclusionDNA damage repair genes were mutated in 40.3% of patients with high-grade serous carcinoma, with somatic BRCA mutations in the absence of germline mutation in 8.5%. Somatic variant examination, along with germline testing of DNA damage repair genes, has potential to detect additional candidates for PARP inhibitor treatment.

Simple Summary Recurrent patients with gynecologic cancer experience a difficult situation when using immune checkpoint inhibitors based on mismatch repair gene immunohistochemistry and microsatellite instability. Six machine learning algorithms were used to create predictive models with seven prospective features (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This provides novel and baseline results of patients with recurrent gynecologic cancer using immune checkpoint inhibitors by using machine learning methods based on Lynch syndrome-related screening markers. Abstract To support the implementation of genome-based precision medicine, we developed machine learning models that predict the recurrence of patients with gynecologic cancer in using immune checkpoint inhibitors (ICI) based on clinical and pathologic characteristics, including Lynch syndrome-related screening markers such as immunohistochemistry (IHC) and microsatellite instability (MSI) tests. To accomplish our goal, we reviewed the patient demographics, clinical data, and pathological results from their medical records. Then we identified seven potential characteristics (four MMR IHC [MLH1, MSH2, MSH6, and PMS2], MSI, Age 60, and tumor size). Following that, predictive models were built based on these variables using six machine learning algorithms: logistic regression (LR), support vector machine (SVM), naive Bayes (NB), random forest (RF), gradient boosting (GB), and extreme gradient boosting (EGB) (XGBoost). The experimental results showed that the RF-based model performed best at predicting gynecologic cancer recurrence, with AUCs of 0.818 and 0.826 for the 5-fold cross-validation (CV) and 5-fold CV with 10 repetitions, respectively. This study provides novel and baseline results about predicting the recurrence of gynecologic cancer in patients using ICI by using machine learning methods based on Lynch syndrome-related screening markers.

Ovarian cancer is one of the leading causes of deaths among patients with gynecological malignancies worldwide. In order to identify prognostic markers for ovarian cancer, we performed RNA-sequencing and analyzed the transcriptome data from 51 patients who received conventional therapies for high-grade serous ovarian carcinoma (HGSC). Patients with early-stage (I or II) HGSC exhibited higher immune gene expression than patients with advanced stage (III or IV) HGSC. In order to predict the prognosis of patients with HGSC, we created machine learning-based models and identified USP19 and RPL23 as candidate prognostic markers. Specifically, patients with lower USP19 mRNA levels and those with higher RPL23 mRNA levels had worse prognoses. This model was then used to analyze the data of patients with HGSC hosted on The Cancer Genome Atlas, this analysis validated the prognostic abilities of these two genes with respect to patient survival. Taken together, the transcriptome profiles of USP19 and RPL23 determined using a machine-learning model could serve as prognostic markers for patients with HGSC receiving conventional therapy.

Background Malignant transformation of endometriosis in extraovarian sites remains rare. Furthermore, the process is not definitely understood. Case presentation Herein, we report the case of a 40-year-old premenopausal nulligravida woman who presented with vaginal bleeding and who was finally diagnosed with a vaginal cancer originating from endometriosis and with a synchronous endometrial cancer. A gynecologic examination revealed a multiple polypoid mass on the posterior vaginal fornix. Magnetic Resonance Imaging of the pelvis showed two masses abutting respectively on the anterior uterine wall, and in the rectovaginal septum. The patient underwent a total laparoscopic excision of the rectovaginal mass, radical hysterectomy and low anterior resection of the rectum. The lesions were diagnosed as endometriosis, endometriosis-associated complex hyperplasia and endometrioid cancer. Furthermore, a synchronous endometrioid endometrial cancer was reported. Conclusions This case revealed the multistep process of malignant transformation of deep infiltrating endometriosis. The progression was individualized between implantation sites and in the same organ.

Objective We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples. Methods This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (

Hyperprolactinemia due to a pituitary adenoma is a rare cause of erectile dysfunction (ED). The prevalence of clinically apparent prolactinomas is reported to be from 6-10 to 50 per 100,000. A few reports have been published of prolactinoma presenting with ED. Here, we report a rare case of a young man who presented with ED as a chief complaint and who was diagnosed with a huge prolactinoma, and we discuss a related fertility issue.

The stromal antigen 3 (STAG3) gene, encoding a meiosis-specific cohesin component, is a strong candidate for causing male infertility, but little is known about this gene so far. We identified STAG3 in patients with nonobstructive azoospermia (NOA) and normozoospermia in the Korean population. The coding regions and their intron boundaries of STAG3 were identified in 120 Korean men with spermatogenic impairments and 245 normal controls by using direct sequencing and haplotype analysis. A total of 30 sequence variations were identified in this study. Of the total, seven were exonic variants, 18 were intronic variants, one was in the 5'-UTR, and four were in the 3'-UTR. Pathogenic variations that directly caused NOA were not identified. However, two variants, c.3669+35C>G (rs1727130) and +198A>T (rs1052482), showed significant differences in the frequency between the patient and control groups (P = 0.021, odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.098-2.918) and were tightly linked in the linkage disequilibrium (LD) block. When pmir-rs1052482A was cotransfected with miR-3162-5p, there was a substantial decrease in luciferase activity, compared with pmir-rs1052482T. This result suggests that rs1052482 was located within a binding site of miR-3162-5p in the STAG3 3'-UTR, and the minor allele, the rs1052482T polymorphism, might offset inhibition by miR-3162-5p. We are the first to identify a total of 30 single-nucleotide variations (SNVs) of STAG3 gene in the Korean population. We found that two SNVs (rs1727130 and rs1052482) located in the 3'-UTR region may be associated with the NOA phenotype. Our findings contribute to understanding male infertility with spermatogenic impairment.

Purpose: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male pa-tients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of se-men quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). Materials and Methods: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully per-formed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and cur-rent banking status. Results: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1–226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreser-vation to use was 51 months (range, 1–158 months). Conclusions: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy.

The incidence of pelvic floor muscle (PFM) dysfunction increases rapidly with menopause and aging. Despite the raised magnitude and prevalence of pelvic floor disorders in middle-aged women, the risk factors underlying PFM dysfunction still remain to be identified. PFM function can be clinically measured as the maximum strength and endurance using manometry. The aim of this study was to evaluate PFM function in terms of strength and endurance by perineometer and to assess the risk factors that decrease PFM strength and endurance in middle-aged women. This was a cross-sectional study. Overall, 125 parous women (age 40–60 years) completed the study. A questionnaire was used to collect information on several demographic and obstetric variables. The Peritron perineometer measured PFM strength and endurance. Multiple linear regression analysis was used to evaluate the effects of sociodemographic variables on PFM function. Both average strength of PFMs and maximum muscle strength significantly reduced as the number of parity increased. Average and maximum strength of PFMs showed a significant difference between women with parities of two and one (β = −0.435, p

Objective To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer.Methods A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups.Results The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC.Conclusion This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.

Phosphodiesterase type 5 (PDE5) inhibitors are effective treatments for erectile dysfunction, and several recent studies have reported positive effects of PDE5 inhibitors on semen parameters as well. However, the data are still controversial. We investigated the effect of PDE5 inhibitors on sperm function by analyzing sperm motility and acrosome reaction.This study included young healthy men who underwent fertility evaluation; 32 cases were finally included. Men were excluded if they used a PDE5 inhibitor within 2 weeks or if they had insufficient semen volume (≤2 mL), leukocytospermia, or a genitourinary infection. Changes in sperm motility and acrosome reaction were determined afterMean age of the participants was 35.4±4.9 years, mean sperm concentration was 68.7±32.4 ×10⁶/mL, and mean sperm motility was 50.38%±8.41%. All three groups (control, sildenafil, tadalafil) experienced trends of decreased average sperm motility over time, but these changes were not significant. There were no significant differences between the three groups in the acrosome reaction after 120 minutes of drug exposure, either. The maximal semen concentration of oral intake of sildenafil (100 mg) or tadalafil (20 mg) did not substantially affect sperm motility or acrosome reaction.Our results suggest that on-demand use of a PDE5 inhibitor is safe and useful for the male partner of an infertile couple; however, further studies are warranted for daily PDE5 inhibitor use.

Purpose We evaluated the efficacy and safety of pembrolizumab in patients with recurrent gynecologic cancers in real-world practice. Materials and methods We conducted a retrospective, single-institution study of patients with recurrent gynecologic malignancies treated with pembrolizumab. The primary endpoints were the objective response rate (ORR) and safety. Results Thirty-one patients treated with pembrolizumab were included. The primary disease sites were the uterine cervix (n=18), ovaries (n=8), and uterine corpus (n=5). Fifteen of the 31 patients (48%) had an Eastern Cooperative Oncology Group performance status of ≥2. The median number of prior chemotherapy lines was 2 (range, 1-6), and 14 of 31 patients (45%) had received ≥ 3 prior lines of chemotherapy. The overall ORR was 22.6%: specifically, 22.3% (4 of 18 patients), 12.5% (1 of 8 patients), and 40% (2 of 5 patients) for cervical, ovarian, and endometrial cancers, respectively. During a median follow-up of 4.7 months (range, 0.2-35.3), the median time to response was 1.9 months (range, 1.4-5.7). The median duration of response was not reached (range, 8.8-not reached). The median progression-free survival was 2.5 months (95% confidence interval, 1.7-not reached). Adverse events occurred in 20 patients (64.5%), and only 3 (9.7%) were grade ≥3. There was one case of suspicious treatment-related mortality, apart from which most adverse events were manageable. Conclusion In real-world practice, pembrolizumab was feasible and effective in heavily treated recurrent gynecologic cancer patients with poor performance status who may not be eligible for enrollment in clinical trials.

Background and objective A small supernumerary marker chromosome (sSMC) is a rare structurally abnormal chromosome in which no part can be identified by conventional cytogenetic banding technique. There is little known about the association of marker chromosomes with male infertility. We performed a molecular cyto-genetic characterization sSMCs and investigated their association with male infertility. Methods Among 4230 infertile male patients who underwent cytogenetic analyses from January 2008 to December 2018, the records of 15 patients who were diagnosed with sSMCs were reviewed. After ini-tial infertility evaluation, the patients received additional genetic tests including G-bands by trypsin using Giemsa (GTG-banding), Nucleolar organizer region (NOR) banding, Fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) analyses to further char-acterize and identify the origin of their marker chromosome. Testis biopsy was performed for the azoospermic patients to evaluate spermatogenic status. Results Among 15 infertile males with sSMCs, eight had nonobstructive azoospermia, five had severe oligozo-ospermia, and two had sperm concentrations above the lower normal limit. The marker chromosomes were identified as Y ring chromosomes (n = 8), an isodicentric Y chromosome (n = 1), a neocen-tromere Y chromosome (n = 1), a derivative chromosome 1 (n = 1), and an acrocentric short arms (n = 4). Conclusion Marker chromosomes appear to be a rare genetic cause of male infertility. Additional cytogenetic tests, including NOR banding, FISH, and aCGH, could help to characterize the origin of the marker chromosome. Appropriate genetic counseling for couples with infertility caused by a marker chromo-some should be recommended.

Background Cancer stem cells (CSCs) can self-renew, proliferate into differentiated cells, or enter a quiescent state and are regarded to cause chemoresistance and recurrence. An integrative analysis of transcription factors (TF) and miRNAs was performed in ovarian CSC-enriched spheroid-forming cells (SFCs) to identify factors relevant to ovarian CSCs. Methods Fresh tumor cells from three ovarian cancer patients were cultured in standard and in selective medium. The mRNAs and miRNAs that exhibited significant differential expression between SFCs and adherent cells were identified using mRNA and miRNAs microarrays. Target genes of miRNAs were further selected if predicted with TargetScan by half of the miRNAs or more. Gene enrichment analysis was performed on over- or under-expressed mRNAs and target genes of miRNAs using DAVID tools. Complex regulatory networks were combined from TF-genes and miRNA-genes interactions using the MAGIA webtool. Results A total of 1245 mRNA and 55 miRNAs were differentially expressed (p-value Conclusions MYC, EGR1, and miR-130a-3p were hubs in our integrative analysis of ovarian CSC-enriched SFCs, suggesting that ovarian cancer SFCs display a stem cell identity with the quiescent phenotype where adhesion- and cell cycle-related genes were suppressed.

The purpose of this study was to identify the sexual behavior and associated factors of Korean female junior high school students. This study design was cross-sectional, and used raw data from the 2013 Korea Youth Risk Behavior Web-based Survey. Among the data from 72,435 students, we analyzed those from 17,609 female junior high school students. Descriptive statistics were used to identify sexual behavior, and χ2-test and logistic regression were used to identify factors related to sexual behavior. Among the female students, 2.5% responded that they had experienced sexual intercourse, and the prevalence of sexual intercourse was higher among mixed-school students than girls’-school students. The students’ risk behaviors or mental health such as drinking, smoking, drug use, depression, and suicidal ideation or attempt showed significant associations whether they had experiences of sexual intercourse or not. Factors which significantly related to students’ likelihood of sexual intercourse were smok...

Aim To identify the association between sexual behavior and suicidal ideation among South Korean middle school students. Methods This study used raw data from the 2013 Korean Youth Risk Behavior Web-Based Survey. Among the data from 72,435 students, the data from 36,530 individuals in middle school were analyzed. The prevalence of sexual behavior and suicidal ideation, according to the participants' general characteristics, and suicidal ideation, according to sexual behaviors, were assessed by using a complex sample Chi-squared test. A complex sample logistic regression was used to examine the association between sexual behavior and suicidal ideation. Results Overall, 3.8% of the students reported having had sexual intercourse and 17.6% of the students reported suicidal ideation during the past 12 months. Having had sexual intercourse was statistically significantly associated with suicidal ideation. The students who had had sexual intercourse usually used contraception and those who had contracted sexually transmitted diseases were more likely to report suicidal ideation in both the unadjusted and adjusted models. Conclusion This study illustrates the need to develop a prevention program that addresses the common factors between sexual behavior and suicidal ideation in order to effectively reduce both sexual behavior and suicidal ideation in middle school students.

Study Objective To evaluate the optimal dose of vaginal misoprostol (200 and 400 µg) for cervical priming before operative hysteroscopy. Design A randomized, controlled, double-blind trial (Canadian Task Force classification I). Setting A university hospital. Patients Sixty-eight patients undergoing operative hysteroscopy. Interventions Patients were randomized to receive a low (200 µg) or high (400 µg) dose of misoprostol administered vaginally 8 hours before operative hysteroscopy. Measurements and Main Results The primary outcome was perioperative dilatation time, and the secondary outcome measurements included the subjective difficulty of cervical dilatation assessed by the surgeon, operative time, self-reported adverse events after vaginal administration and before the start of the operation, and complications during the procedure. A comparison of the 200-µg (n = 34) and 400-µg (n = 34) misoprostol cohorts revealed similarities when comparing time with cervical dilatation, operative difficulty, result, and time. Misoprostol-related adverse events were significantly lower in the 200-µg cohort than the 400-µg cohort (58.8% vs 85.3%, p = .015). Abdominal pain was the most common adverse event and was higher in the 400-µg cohort compared with the 200-µg cohort (73.5% vs 50.0%, p = .046). However, there were no operative delays resulting from adverse events, and all individuals reported the procedure to be tolerable and recovered without medication or treatment. Conclusion Both 200 µg and 400 µg vaginally administered misoprostol are effective for cervical dilatation, and we recommend vaginal administration of 200 µg misoprostol for cervical dilatation 8 hours before operative hysteroscopy because of lower adverse events in the 200-µg group as well as similar efficacy between cohorts.

Objective The aim of the present study was to investigate unclassified variants (UVs) in BRCA1 and 2 of Korean patients with ovarian cancer. Methods We retrospectively analyzed 138 patients diagnosed with ovarian/fallopian tubal/peritoneal cancer between January 2013 and January 2016, whose BRCA genetic test results and clinical characteristics were available for review. Patient peripheral blood lymphocyte specimens were assessed for BRCA mutations and variations by direct sequencing. Identified UVs were classified according to several algorithms. Results The results of genetic testing revealed 31 (22.5%, 31/138) pathogenic BRCA mutations (24 BRCA1, 7 BRCA2 mutations). The BRCA1 c.390C>A mutation was observed in 4 patients (12.9%, 4/31). Thirty-four (24.6%, 34/138) BRCA UVs were identified in 33 patients. Of these, the BRCA1 c.4883T>C and BRCA2 c.8187G>T variants were each detected in 4 patients (4/34, 11.8%). According to the used algorithms and cosegregation test, the BRCA1 c.5339T>C and BRCA2 c.8437_8439delGGA variants were both predicted to be likely pathogenic. Conclusions The 2 identified likely pathogenic UVs require further verification with clinical evidence. Clarifying the clinical significance of UVs is an increasingly important step for cancer treatment in the current era of precision medicine.

Background - Despite preventive HPV vaccines is implemented worldwide, current treatments for high grade cervical intraepithelial neoplasia are ablative, and no pharmacological treatments are available. Here we evaluated safety of BLS-ILB-E710c, HPV 16 E7-expressing Lactobacillus-based vaccine, and explored its efficacy for histopathological regression in women with CIN2/3. Methods - Safety and efficacy of BLS-ILB-E710c were assessed in CIN2/3 associated with HPV16 and its related HPV types in a randomized, double-blind, placebo-controlled phase 2b study. Total of 116 patients was recruited from fourteen hospitals in South Korea, and were randomized (2:1) to receive 1000 mg BLS-ILB-E710c or placebo for 5 days at 1, 2, 4, and 8 weeks. The primary endpoint was histopathological regression to CIN1 or normal pathology at 16 weeks after the first dose. Full analysis set (FAS) and Per-protocol set (PPS) analyses were based on patients receiving at least one oral vaccination, and on patients receiving four rounds of oral vaccination without protocol violations, respectively. The safety population included all patients who enrolled. The trial is registered at clinicaltrials.gov (number NCT03274206). Findings - Total of 116 patients were randomized, and 113 received either BLS-ILB-E710c (n=75) or placebo (n=38). The oral vaccination was well tolerated and no serious vaccine-related AEs occurred. No differences were showed between the BLS-ILB-E710c and placebo groups for patient background and adverse events. In the full analysis set (FAS) no statistically significant difference was noted between the two groups of histopathological regression at 16 weeks. However, the distribution by Bethesda system (for cervical cytology) in CIN2 patients showed significant differences between two groups (P=0.0304), which can affect histopathological regression. Sub-group analysis in FAS is performed to reduce the bias; histopathological classification (CIN2, CIN3) and cytological classification (≤ASCUS, LSIL, HISL). Therefore, in CIN3 sub-group, BLS-ILB-E710c recipients showed 13.33% of higher histopathological regression at 32 weeks than placebo recipients, and interestingly represented the statistically significant difference when histopathological regression at 32 weeks compared with 16 weeks (percentage point difference 34.87 [95% CI 7.78–61.96]; P=0.0216). In BLS-ILB-E710c recipients of CIN3 sub-group with histopathological regression, E7-specific CD8+ T lymphocyte immune responses were induced at 32 weeks (P= 0.0323). In addition, in HSIL sub-group, BLS-ILB-E710c recipients showed higher histopathological regression at 32 weeks than placebo recipients in similar with CIN3 sub-group analysis. Interpretation – Based on the finding this study, BLS-ILB-E710c could induce the local immune response by recruiting HPV16 E7-specific CD8+ T cells to cervical lesions, leading to histologic regression. To assess the efficacy of BLS-ILB-E710c as a novel Lactobacillus-based oral vaccine, it is necessary to define the population and time frame for phase 3 trial. Citation Format: Jae Kwan Lee, Seung Hun Song, Young Tae Kim, Chi-Heum Cho, Chan Joo Kim, Young-Chul Park. A double-blind randomized, placebo-controlled trial of oral administration with human papillomavirus (HPV) type 16 E7-expressing Lactobacillus-based vaccine, BLS-ILB-E710c, for the treatment of cervical intraepithelial neoplasia (CIN2/3) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P043.

Fibroepithelial polyp (FEP) and lymphangioma circumscriptum (LC) of the vulva are rare diseases that occur generally in young to middle-aged women. The pathogenesis of FEP is not clearly understood. Several previous cases have suggested that a hormonal influence may be a predisposing condition for developing FEP with or without chronic inflammation. A 68-year-old postmenopausal woman presented with a history of multiple raised lesions on the vulva with a 1-year duration. Additionally, a pedunculated mass had appeared 6 months earlier in the left lower labia minora. The patient underwent simple excision by electrocautery. The final pathological diagnosis was FEP with LC. In this case, the development of FEP was associated only with chronic inflammation induced by LC. Therefore, the case supports the hypothesis that a chronic inflammatory process may be related to the development of FEP even without hormonal influence.

Isolated torsion of the fallopian tube in postmenopausal women is rare. In this case report, we detail the case of a 53-year-old patient who presented with adenomyosis and a left hydrosalpinx with high levels of CA 125 and CA 19-9. The isolated torsion of the left hydrosalpinx was observed during the operation. The serum levels of CA 125 and CA 19-9 were reduced from 129.62 and 348 to 58.2 and 12.41 U/mL, respectively, after total laparoscopic hysterectomy with salpingectomy. On radiologic evaluation, there were no other factors that may have influenced the increase in serum levels of CA 125 and CA 19-9 in this patient, which were reduced after operation. To the best of our knowledge, this is the first case of association between perioperative changes in CA 19-9 levels and isolated torsion of the fallopian tube.

Background and objectives Surgical smoke contains various malodorous and hazardous combustion byproducts. We aimed to analyze hydrocarbons accumulated in the abdominal cavity during laparoscopic gynecologic surgery and determine the efficiency of a built-in-filter port. Methods We prospectively followed seven patients with benign uterine pathology. Surgical smoke was generated using laparoscopic or robotic electrocautery. The smoke was collected twice for each patient using a built-in-filter port and a conventional port. The concentrations of volatile organic compounds and aldehydes were determined using gas chromatography with mass spectrometry and high-performance liquid chromatography with ultraviolet visible light detection and compared using the paired-sample Wilcoxon signed-rank test. Results Five volatile organic compounds and five aldehydes had toxic effects or unpleasant odors. The median concentration of formaldehyde before filtration (0.870 ppm) exceeded the time-weighted average concentration (0.75 ppm) of the Occupational Safety and Health Administration. Built-in-filter ports significantly reduced the concentration of five volatile organic compounds and two aldehydes but not that of formaldehyde, acetaldehyde, and propionaldehyde. Formaldehyde concentration decreased by 50% after filtration but remained above the recommended exposure limit (0.016 ppm) of the National Institute of Occupational Safety and Health. Conclusions Surgical smoke in minimally invasive gynecologic procedures contains several hazardous hydrocarbons including formaldehyde. Built-in-filter ports have the potential to reduce the exposure of surgical smoke to surgeons and operating room personnel; nevertheless, development of built-in-filter ports is necessary to improve the filtering efficiency for highly concentrated formaldehydes.