Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer.

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.

Placental Site Trophoblastic Tumors: Analysis of the Clinicopathologic Characteristics of 20 Cases in Korea.

OBJECTIVES: The aim of this study was to evaluate the clinicopathologic features of placental site trophoblastic tumors (PSTTs) in Korea. METHODS/MATERIALS: Twenty patients given a diagnosis of PSTT in Korea (1990-2013) were evaluated retrospectively, including 14 patients identified through a literature review and 6 patients identified through a medical chart review of a single institution. The analysis included patient age, antecedent pregnancies, time since antecedent pregnancy, presenting symptoms, serum ß-human chorionic gonadotropin level, International Federation of Gynecology and Obstetrics stage, treatment, outcome, and follow-up. RESULTS: The mean age of the 20 patients was 32 years (range, 25-53 years). The antecedent pregnancies included 8 term pregnancies, 8 abortions, and 2 molar pregnancies. The time since the antecedent pregnancy was less than 1 year in 16 patients (80%). Nineteen patients (95%) presented with abnormal vaginal spotting or amenorrhea. Serum ß-human chorionic gonadotropin levels ranged from normal to 13,480 mIU/mL, although most patients (80%) had a level less than 1000 mIU/mL. Seventeen patients (85%) presented with stage I disease. Ten patients (50%) underwent hysterectomy, and 14 patients (70%) were treated with chemotherapy with or without hysterectomy. In 11 evaluated patients, the median mitotic count index was 3.4 (0.4-10) per 10 high-power fields. The median follow-up time was 17 months (range, 1-68 months). There was no recurrence or death from disease. CONCLUSIONS: Korean patients with PSTT often have early-stage disease, which has a favorable prognosis even with fertility-preserving therapy. However, international studies are necessary to determine the optimal treatment and prognostic factors.

Microscopic Omental Metastasis in Clinical Stage I Endometrial Cancer: A Meta-analysis.

BACKGROUND: A patient with early-stage endometrial cancer may possibly have microscopic metastasis in the omentum, which is associated with a poor prognosis. The purpose of this study was to identify risk factors for microscopic omental metastasis in patients with clinical stage I endometrial cancer to establish the indications for selective omentectomy. METHODS: We searched the PubMed, EMBASE, and Cochrane Library databases for published studies from inception to August 2014, using terms such as 'endometrial cancer' or 'uterine cancer' for disease, 'omentectomy' or 'omental biopsy' for intervention, and 'metastasis' for outcome. Two reviewers independently identified the studies that matched the selection criteria. We calculated the pooled risk ratios (RRs) with 95 % confidence intervals (CI) of each surgicopathologic finding for microscopic omental metastases in clinical stage I endometrial cancer. We also calculated the prevalence of microscopic omental metastases. RESULTS: Among 1163 patients from ten studies, 22 cases (1.9 %) of microscopic omental metastases were found, which accounted for 26.5 % of all omental metastases. Positive lymph nodes (RR 8.71, 95 % CI 1.38-54.95), adnexal metastases (RR 16.76, 95 % CI 2.60-107.97), and appendiceal implants (RR 161.67, 95 % CI 5.16-5061.03) were highly associated with microscopic omental metastases. CONCLUSIONS: Microscopic omental metastases were not negligible in patients with clinical stage I endometrial cancer. Those with a risk factor of microscopic omental metastases were recommended for selective omentectomy.

Comparison of diagnostic accuracy between endometrial curettage and pipelle aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group Study (KGOG 2019).

A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months.

Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.

OBJECTIVES: To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group. METHODS/MATERIALS: One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing. RESULTS: BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history.Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%). CONCLUSIONS: The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

BACKGROUND AND OBJECTIVE: We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. STUDY DESIGN/MATERIALS AND METHODS: Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm2 . RESULTS: The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. CONCLUSIONS: PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. 47:566-570, 2015. © 2015 Wiley Periodicals, Inc.

Dysregulated microRNA expression in adenocarcinoma of the uterine cervix: clinical impact of miR-363-3p.

OBJECTIVE: Adenocarcinoma (ACA) of the uterine cervix is increasing in incidence and currently accounts for approximately 20% of all cervical malignancies. MicroRNAs (miRNAs) have been investigated as potential biomarkers of cervical cancer; however, their role in ACA remains unknown. Here, we characterized miRNA expression profiles and investigated miRNAs as diagnostic and prognostic factors in ACA. METHODS: Evaluation of genome-wide miRNA expression profiles in ACA by microarray led to the identification of ten candidate miRNAs, whose expression patterns were validated by qRT-PCR in 45 ACA, 10 normal control, and 15 squamous cell carcinoma samples. The association between miRNA expression and prognosis was analyzed in patients with ACA. RESULTS: Microarray analysis identified 86 miRNAs that were dysregulated more than 2.0-fold (p<0.05) in ACA relative to normal tissues of the uterine cervix. Five most over- and underexpressed miRNAs were selected respectively and their expression patterns were confirmed in the validation set. MiR-135b, miR-192, and miR194 were overexpressed in ACA, and miR-363-3p, miR-195 and miR-199b were significantly associated with conventional prognostic factors. Overexpression of miR-363-3p by more than 2.5-fold relative to the normal control was a strong predictor of favorable prognosis (hazard ratio, 0.1; 95% confidence interval, 0.009-0.779) after adjusting for confounders. CONCLUSIONS: MiR-135b, miR-192, and miR-194 are altered in uterine cervical ACA, and miR-363-3p is an independent favorable prognostic factor in ACA. These miRNAs could be of value as biomarkers for the diagnosis and prognosis of ACA.

Ectopic over-expression of tristetraprolin in human cancer cells promotes biogenesis of let-7 by down-regulation of Lin28.

Tristetraprolin (TTP) is a AU-rich element (ARE) binding protein and exhibits suppressive effects on cell growth through down-regulation of ARE-containing oncogenes. The let-7 microRNA has emerged as a significant factor in tumor suppression. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. In this work, an unexpected link between TTP and let-7 has been found in human cancer cells. TTP promotes an increase in expression of mature let-7, which leads to the inhibition of let-7 target gene CDC34 expression and suppresses cell growth. This event is associated with TTP-mediated inhibition of Lin28, which has emerged as a negative modulator of let-7. Lin28 mRNA contains ARE within its 3'-UTR and TTP enhances the decay of Lin28 mRNA through binding to its 3'-UTR. This suggests that the TTP-mediated down-regulation of Lin28 plays a key role in let-7 miRNA biogenesis in cancer cells.

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology consensus statement.

The Korean Society of Gynecologic Oncology (KSGO) had been making an effort to standardize and enhance the quality of domestic uterine corpus cancer treatment by developing updated clinical practice guidelines in 2021. The KSGO revised the guidelines based on a literature search using 4 key elements: Population, Intervention, Comparison, and Outcome framework. These elements include the evaluation of the efficacy and safety of immune checkpoint inhibitor treatment in recurrent/advanced endometrial cancer patients who have failed platinum-based chemotherapy, as well as the effect of combined treatment with trastuzumab in patients with HER2/neu-positive endometrial cancer. Additionally, the guideline assessed the efficacy and safety of omitting lymph node dissection in low-risk endometrial cancer patients, investigated the effect of sentinel lymph node mapping in early-stage endometrial cancer surgery, addressed the outcome of chemoradiation therapy as a postoperative treatment in patients with advanced (stage III-IVA) endometrial cancer, and explored the impact of initial treatment with immune checkpoint inhibitors on survival in patients with advanced or recurrent endometrial cancer patients.

Laparoendoscopic single-site versus conventional laparoscopic gynecologic surgery: a metaanalysis of randomized controlled trials.

OBJECTIVE: To assess the current evidence regarding the efficiency, safety, and potential advantages of laparoendoscopic single-site surgery (LESS) for treating gynecologic diseases. STUDY DESIGN: We comprehensively searched PubMed, Embase, and the Cochrane Library from their inception to December 2012. Two authors screened out duplicates and independently reviewed eligibility of each study. We included randomized controlled trials comparing LESS with conventional laparoscopy (CL) for treating gynecologic diseases. The primary outcomes were perioperative complication rate, conversion rate, postoperative pain, and cosmetic satisfaction. RESULTS: We included 6 randomized controlled trials with 439 participants in the final analysis. There were no significant differences between LESS and CL in terms of perioperative complication rate (15.5% and 14.3%; risk ratio, 1.11; 95% confidence interval [CI], 0.74-1.67; P = .61), conversion rate (3.8% and 1.1%; risk ratio, 2.75; 95% CI, 0.73-10.33; P = .13), postoperative pain (weighted mean difference [WMD], -0.22; 95% CI, -1.29 to 0.85; P = .68), analgesic requirement (WMD, 0.41; 95% CI, -1.69 to 2.51; P = .70), and cosmetic satisfaction (WMD, 0.19; 95% CI, -0.30 to 0.68; P = .46). There were also no differences in terms of operative time (P = .65), hemoglobin change (P = .23), time to first flatus (P = .17), and length of hospital stay (P = .99) between both techniques. CONCLUSION: This metaanalysis provides evidence that LESS is comparable in the efficacy and safety, but does not offer potential advantage such as better cosmesis and lesser pain compared with CL for treating gynecologic diseases.

Single-port access total laparoscopic hysterectomy for large uterus.

BACKGROUND/AIMS: To evaluate the feasibility and safety of single-port access total laparoscopic hysterectomy (SPA-TLH) for large uterus (>500 g). METHODS: A prospective data collection was performed in 21 consecutive patients in March 2010 and August 2011. Surgical outcome including operative time (OT) and estimated blood loss (EBL) were analyzed. RESULTS: SPA-TLH procedures were successfully performed in 16 cases (76.2%). Of the 5 failed cases, 4 were converted to multiport TLH because of distorted uterine contours and pelvic adhesions and 1 was converted to laparotomy for bleeding control. The median OT, uterine weight, and EBL were 110 (65-165) min, 600 (502-980) g, and 200 (100-800) ml, respectively. Spearman's correlation analysis demonstrated that OT and blood loss increased with increasing uterine weight (p = 0.003 and p = 0.033, respectively). No operative complications were observed during the hospital stay and 3-month follow-up following discharge. CONCLUSION: SPA-TLH for large uterus is a feasible and safe technique.

Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies.

PURPOSE: We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. RESULTS: The median age of the patients was 56 years (range, 35-79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4-49.6). Reasons for first ICI discontinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4-10.4). The median overall survival was 21.3 months (range, 10.1-52.7). Neither patient who discontinued ICI treatment due to AEs experienced AE relapse during second ICI treatment. CONCLUSION: These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely support this practice.

The Association Between the Number of Retrieved Pelvic Lymph Nodes and Ipsilateral Lower Limb Lymphedema in Patients With Gynecologic Cancer.

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.

Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test.

We aimed to investigate the prevalence and relative contributions of LS and non-LS mutations in patients with endometrial cancer in Korea. We retrospectively reviewed the medical records of 204 patients diagnosed with endometrial cancer who underwent a germline next generation sequencing multigene panel test covering MLH1, MSH2, MSH6, PMS2, and EPCAM at three tertiary centers. Thirty patients (14.7%) with pathogenic mutations (12 MLH1; 6 MSH2; 10 MSH6; 2 PMS2) and 20 patients (9.8%) with 22 unclassified variants (8 MLH1; 8 MSH2; 2 MSH6; 3 PMS2; 1 EPCAM) were identified. After excluding four close relatives of a proband, the prevalence of LS was 13.0% (26/200). Patients with LS were more likely than those with sporadic cancer to be younger at diagnosis (48 vs. 53 years, p = 0.045) and meet the Amsterdam II criteria (66.7 vs. 3.5%, p < 0.001). Non-endometrioid histology was more prevalent in patients with MSH6 or PMS2 mutations (41.7%) than those with MLH1 or MSH2 mutations (5.6%, p = 0.026). In this pre-selected cohort of endometrial cancer patients who underwent next generation sequencing, the prevalence of LS was 13%, thus supporting the use of gene panel testing for endometrial cancer patients.

Long Non-Coding RNA-Based Functional Prediction Reveals Novel Targets in Notch-Upregulated Ovarian Cancer.

Notch signaling is a druggable target in high-grade serous ovarian cancers; however, its complexity is not clearly understood. Recent revelations of the biological roles of lncRNAs have led to an increased interest in the oncogenic action of lncRNAs in various cancers. In this study, we performed in silico analyses using The Cancer Genome Atlas data to discover novel Notch-related lncRNAs and validated our transcriptome data via NOTCH1/3 silencing in serous ovarian cancer cells. The expression of novel Notch-related lncRNAs was down-regulated by a Notch inhibitor and was upregulated in high-grade serous ovarian cancers, compared to benign or borderline ovarian tumors. Functionally, Notch-related lncRNAs were tightly linked to Notch-related changes in diverse gene expressions. Notably, genes related to DNA repair and spermatogenesis showed specific correlations with Notch-related lncRNAs. Master transcription factors, including EGR1, CTCF, GABPα, and E2F4 might orchestrate the upregulation of Notch-related lncRNAs, along with the associated genes. The discovery of Notch-related lncRNAs significantly contributes to our understanding of the complex crosstalk of Notch signaling with other oncogenic pathways at the transcriptional level.

Frequency of Mismatch Repair Deficiency/High Microsatellite Instability and Its Role as a Predictive Biomarker of Response to Immune Checkpoint Inhibitors in Gynecologic Cancers.

PURPOSE: This 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 METHODS: We 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. RESULTS: Among 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). CONCLUSION: The 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.

Peroxiredoxin 6 overexpression attenuates cisplatin-induced apoptosis in human ovarian cancer cells.

We examined the involvement of peroxiredoxin 6 (Prdx 6) in providing chemoprotection against cisplatin cytotoxicity in SKOV-3 ovarian cancer cells. Treatment of SKOV-3 cells with cisplatin-induced cytotoxicity that was associated with increased accumulation of intracellular reactive oxygen species (ROS) and apoptosis mediated by proteolytically activated caspase 3 and 9. Overexpression of Prdx 6 protein or exposure to N-acetylcysteine (NAC) reversed the apoptotic effect of cisplatin by reducing ROS levels and suppressing the caspase signaling pathway. These results indicate that targeting Prdx 6 may sensitize cancer cells to ROS-producing therapeutic treatments, such as anticancer drugs and radiation.

Hepatic resection as part of secondary cytoreductive surgery for recurrent ovarian cancer involving the liver.

PURPOSE: The aims of this study were to assess the surgical outcomes and to also determine the prognostic factors in patients with surgically resectable liver metastases for recurrent ovarian cancer. METHODS: Between 1991 and 2008, 18 patients with recurrent ovarian cancer who underwent hepatic resection as part of secondary cytoreductive surgery were identified from the tumor registry pathology database. Parameters for safety, efficacy, and survival data were considered as primary endpoints. RESULTS: Hepatic resections included wedge resection (n = 4), unisegmentectomy (n = 13), and bisegmentectomy (n = 1). There were no surgery-related deaths. Only one patient (5.6%) had postoperative major complications. The median postoperative hospitalization was 15.5 days (range 11-46 days). The prognostic factors associated with improved survival were less abdominal than pelvic disease (38 vs. 11 months, P = 0.032), optimal cytoreduction (40 vs. 9 months, P = 0.0004), and negative margin status of the hepatic resection (40 vs. 9 months, P = 0.0196). The overall median survival after hepatic resection was 38 months (range 3-78 months). CONCLUSION: Hepatic resection for recurrent ovarian cancer is safe and is associated with a favorable outcome. Parenchymal liver metastases should not exclude attempts at optimal secondary cytoreductive surgery, and especially, patients with solitary liver metastases should be considered for hepatic resection.

Machine Learning for Recurrence Prediction of Gynecologic Cancers Using Lynch Syndrome-Related Screening Markers.

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.

Hyperthermic intraperitoneal chemotherapy as consolidation treatment of advanced stage ovarian cancer.

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.