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.

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines.

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.

Endothelial periostin regulates vascular remodeling by promoting endothelial dysfunction in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with extracellular matrix (ECM) deposition, vascular cell hyperproliferation, and neointima formation in the small pulmonary artery. Endothelial dysfunction is considered a key feature in the initiation of vascular remodeling. Although vasodilators have been used for the treatment of PAH, it remains a life-threatening disease. Therefore, it is necessary to identify novel therapeutic targets for PAH treatment. Periostin (POSTN) is a secretory ECM protein involved in physiological and pathological processes, such as tissue remodeling, cell adhesion, migration, and proliferation. Although POSTN has been proposed as a potential target for PAH treatment, its role in endothelial cells has not been fully elucidated. Here, we demonstrated that POSTN upregulation correlates with PAH by analyzing a public microarray conducted on the lung tissues of patients with PAH and biological experimental results from in vivo and in vitro models. Moreover, POSTN overexpression leads to ECM deposition and endothelial abnormalities such as migration. We found that PAH-associated endothelial dysfunction is mediated at least in part by the interaction between POSTN and integrin-linked protein kinase (ILK), followed by activation of nuclear factor-κB signaling. Silencing POSTN or ILK decreases PAH-related stimuli-induced ECM accumulation and attenuates endothelial abnormalities. In conclusion, our study suggests that POSTN serves as a critical regulator of PAH by regulating vascular remodeling, and targeting its role as a potential therapeutic strategy for PAH.

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis.

OBJECTIVES: This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients. METHODS/MATERIALS: A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis. RESULTS: The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63). CONCLUSIONS: In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.

Ginsenoside Rg3 attenuates pulmonary fibrosis by inhibiting endothelial to mesenchymal transition.

Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and fibroblast proliferation. Endothelial-to-mesenchymal transition (EndMT) serves as a source of fibroblasts and contributes to PF progression. Ginsenoside Rg3 (Rg3), a steroidal saponin extracted from ginseng, is known to have pharmacological effects on vascular diseases. We have previously demonstrated that Rg3 inhibits EndMT and prevents endothelial dysfunction. Thus, we hypothesized that Rg3 may be a potential therapeutic agent for PF-targeting EndMT. EndMT occurs in the lung tissue of a bleomycin-induced PF mouse model, which was confirmed by co-staining of endothelial and mesenchymal markers in the pulmonary vasculature and changes in the expression of these markers. Rg3 administration decreased EndMT and suppressed PF development. We also examined the effect of Rg3 in an in vitro EndMT model induced by co-treatment with TGF-ß2 and IL-1ß. Rg3 treatment alleviated the characteristics of EndMT such as spindle-shaped morphological changes, EndMT marker expression changes, Dil-Ac-LDL uptake and migratory properties. In addition, we demonstrated the mechanism by which Rg3 inhibits EndMT by regulating the Smad2/3 signaling pathway. Collectively, Rg3 can be a potential therapeutic agent for PF using the EndMT inhibition strategy, furthermore, it can be considered Rg3 as a therapeutic candidate for various EndMT-associated vascular diseases.

Diagnostic efficacy of aneuploidy markers correlated with early onset preeclampsia.

Low-dose aspirin administration before 16 weeks of gestation can prevent preeclampsia (PE) more effectively. In order to determine if aspirin should be administered, this study aimed to investigate the predictive value of pregnancy-associated plasma protein A (PAPP-A) and aneuploidy markers for the onset period of PE. 1053 singleton pregnant women were included in the study, and serum PAPPA-A and aneuploidy markers were analyzed between 3 group (normotensive, late-onset PE, and early-onset PE). The utility of these markers for predicting early-onset preeclampsia (EOPE) was compared using each marker and their combination. Alpha-fetoprotein (AFP)/PAPP-A > 6.89 and human chorionic gonadotropin (hCG)/PAPP-A > 7.94 were associated with EOPE with a positive likelihood ratio (LR) (6.52, 95% confidence interval [CI] 4.9-7.1), and (5.77, 95% CI 3.9-6.4). The combination of markers could predict EOPE more accurately compared to the single markers. AFP/PAPP-A > 6.89 and hCG/PAPP-A > 7.94had a predictive ability for EOPE, and these cutoff values can help determine the use of aspirin at an earlier gestational age (GA).

MicroRNA-dependent inhibition of WEE1 controls cancer stem-like characteristics and malignant behavior in ovarian cancer.

Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. Although WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed on the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment.

Clinicopathologic significance of DNA mismatch repair protein status in endometrial cancer.

OBJECTIVE: The prognostic implications of DNA mismatch repair protein (MMRP) have not been determined in endometrial cancer. Therefore, in this study, we aimed to evaluate the clinicopathologic characteristics of DNA MMRP deficiency in endometrial cancer. MATERIALS AND METHODS: We examined the MMRP status of 206 patients with endometrial carcinomas, using immunohistochemistry, and analyzed their clinicopathologic factors and survival outcomes stratified by MMRP status using the Kaplan-Meier method and Cox regression analysis. RESULTS: Forty-three cases were deficient for at least one MMRP (20.9%). Loss of MLH1 was the most common (13.1%), followed by MSH6 (7.8%). MMRP deficiency was significantly associated with lympho-vascular space invasion, deep myometrial invasion, and adjuvant treatment (P = 0.032, 0.041, and 0.047, respectively). MMRP-deficient patients had a better overall survival (OS), particularly at advanced cancer stages (III/IV) (100% vs. 73.7%, P = 0.170) or if they had received adjuvant treatment (100% vs. 86.7%, P = 0.087). CONCLUSION: Although MMRP deficiency was associated with unfavorable prognostic risk factors in endometrial cancer, we found a trend in favor of OS in MMRP-deficient patients. More studies are needed to confirm its prognostic implication.

Plasma-activated medium inhibits cancer stem cell-like properties and exhibits a synergistic effect in combination with cisplatin in ovarian cancer.

Ovarian cancer stem-like cells (CSCs) have been implicated in tumor recurrence, metastasis, and drug resistance. Accumulating evidence has demonstrated the antitumor effect of plasma-activated medium (PAM) in various carcinomas, including ovarian cancer. Thus, PAM represents a novel onco-therapeutic strategy. However, its impact on ovarian CSCs is unclear. Here, we show that ovarian CSCs resistant to high-dose conventional chemotherapeutic agents used for ovarian cancer treatment exhibited dose-dependent sensitivity to PAM. In addition, PAM treatment reduced the expression of stem cell markers and sphere formation, along with the aldehyde dehydrogenase- or CD133-positive cell population. We further investigated the effect of PAM in combination with other chemotherapeutics on ovarian CSCs in vitro. PAM exhibited synergistic cytotoxicity with cisplatin (CDDP) but not with paclitaxel and doxorubicin. In a peritoneal metastasis xenograft model established via intraperitoneal spheroid injection, PAM intraperitoneal therapy significantly suppressed peritoneal carcinomatosis (tumor size and number), with a more significant decrease observed due to the combined effects of PAM and CDDP with no side effects. Taken together, our results indicate that PAM inhibits ovarian CSC traits and exhibits synergetic cytotoxicity with CDDP, demonstrating PAM as a promising intraparietal chemotherapy for enhancing antitumor efficacy and reducing side effects.

An empyema caused by Streptococcus constellatus in an older immunocompetent patient: Case report.

RATIONALE: Empyema caused by Streptococcus constellatus is rare in patients without underlying diseases. However, the importance of the Streptococcus anginosus group, which consists of S constellatus, S anginosus, and Streptococcus intermedius, as causative organisms of empyema has been increasing. PATIENT CONCERNS: A 78-year-old man initially presented with dyspnea and chills for 4 days. He had no medical history. DIAGNOSIS: Chest X-ray and chest computed tomography showed a large and multiloculated pleural effusion with an air bubble on the right side. Cultivation of the pleural effusion using clone library analysis of the 16S rRNA gene revealed S constellatus positivity. INTERVENTIONS: The patient was treated by drainage of the pleural effusion and intravenous ceftriaxone and clindamycin for the possibility of anaerobes, followed by 10 weeks of oral antibiotics. OUTCOMES: On the 11th day of admission, the thoracic drainage tube was removed. After 1 year of treatment, there were no sequelae of empyema. LESSONS: Although S constellatus can cause serious infections in patients with underlying diseases and immunosuppression, physicians need to consider S constellatus infection in community-acquired empyema in elderly individuals. It should be treated with early pleural drainage and antibiotics to avoid surgical decortication and prolonged hospitalization.

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.

Clinical approach and management of uterine incarceration according to trimester of pregnancy: Case report and literature review.

OBJECTIVE: The purpose of present report is an effective clinical approach to incarcerated uterus by the trimester of pregnancy, in this case and 54 cases reported previously. CASE REPORT: A woman at 18 + 5 weeks of gestation was referred with abdominal pain and urinary dysfunction. In pelvic examination, the cervix was not seen and huge myoma was located at retroverted anterior uterine wall and the elongated cervix was pulled up above the bladder in ultrasonography. The uterine incarceration was confirmed by magnetic resonance imaging. The manual reduction of uterus was attempted with knee-chest-position repeatedly. However, this was unsuccessful because large fibroid was impacted and immovable. Therefore, laparotomy was conducted for repositioning of uterus. Pregnancy was maintained without any complication and a 4250 g healthy female infant was delivered by cesarean section. CONCLUSION: By analyzing of several cases, useful diagnostic modalities and effective management should be approached according to trimester of pregnancy.

MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells.

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial-mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a-AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.

Comparison of long-term survival of total abdominal radical hysterectomy and laparoscopy-assisted radical vaginal hysterectomy in patients with early cervical cancer: Korean multicenter, retrospective analysis.

PURPOSE: The aim of this study was to compare survival outcomes of total abdominal radical hysterectomy (TARH) versus laparoscopy-assisted radical vaginal hysterectomy (LARVH) in stage IA2-IB2 cervical cancer. METHODS: 812 patients who underwent RH between 2008 and 2017 were evaluated in 3 institutions. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier method and compared by log-rank test. The clinical noninferiority of the LARVH to TARH was assessed with a margin of -7.2%. Noninferiority was demonstrated if the low limit of 95% confidence interval (CI) exceeded its predefined margin. RESULTS: 258 patients were treated with TARH and 252 patients with LARVH. TARH and LARVH group had similar 5-year PFS (84.4% vs 86.6%, p = 0.467) and OS rates (85.8% vs 88.0%, p = 0.919). Noninferiority of LARVH to TARH were confirmed with 5-year PFS and OS difference rates of 2.2% (95% CI -2.9-7.3, p = 0.001) and 2.2% (95% CI -2.7-7.1, p = 0.001), respectively. In subgroup of patients with tumors size >2 cm, 5-year PFS (77.6% vs 79.0%, p = 0.682) and OS rates (79.2% vs 81.5%, p = 0.784) did not differ statistically between the two groups. Noninferiority of LARVH to TARH were also confirmed with 5-year PFS and OS difference rates of 1.4% (95% CI -7.0-9.8, p = 0.046) and 2.3% (95% CI -5.8-10.4, p = 0.027), respectively. CONCLUSION: LARVH showed significant noninferiority for PFS and OS versus TARH in early cervical cancer, suggesting the potential oncologic safety of LARVH.

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.

Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer.

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [BMB Reports 2020; 53(6): 291-298].

MiR-146a Regulates Migration and Invasion by Targeting NRP2 in Circulating-Tumor Cell Mimicking Suspension Cells.

Cancer metastasis is the primary cause of cancer-related death and metastatic cancer has circulating-tumor cells (CTCs), which circulate in the bloodstream before invading other organs. Thus, understanding the precise role of CTCs may provide new insights into the metastasis process and reduce cancer mortality. However, the molecular characteristics of CTCs are not well understood due to a lack of number of CTCs. Therefore, suspension cells were generated from MDA-MB-468 cells to mimic CTCs, and we investigate the microRNA (miRNA)-dependent molecular networks and their role in suspension cells. Here, we present an integrated analysis of mRNA and miRNA sequencing data for suspension cell lines, through comparison with adherent cells. Among the differentially regulated miRNA-mRNAs axes, we focus on the miR-146a-Neuropilin2 (NRP2) axis, which is known to influence tumor aggressiveness. We show that miR-146a directly regulates NRP2 expression and inhibits Semaphorin3C (SEMA3C) signaling. Functional studies reveal that miR-146a represses SEMA3C-induced invasion and proliferation by targeting NRP2. Finally, high-NRP2 is shown to be associated with poor outcomes in breast cancer patients. This study identifies the key role of the miR-146a-NRP2 signaling axis that is critical for the regulation of migration and invasion in CTC-mimicking cells.

Clinical Usefulness of Cancer Antigen (CA) 125, Human Epididymis 4, and CA72-4 Levels and Risk of Ovarian Malignancy Algorithm Values for Diagnosing Ovarian Tumors in Korean Patients With and Without Endometriosis.

BACKGROUND: Tumor markers are useful for detection and preoperative evaluation of ovarian tumors. We evaluated the clinical usefulness of cancer antigen (CA) 125, human epididymis 4 (HE4), and CA72-4 levels and Risk of Ovarian Malignancy Algorithm (ROMA) values for differential diagnosis of malignant and borderline tumors among suspected ovarian tumors, and the effects of endometriosis on these tumor markers. METHODS: In a total of 266 patients (213, 14, and 39 with benign, borderline and malignant tumors, respectively), CA125, HE4, and CA72-4 levels were measured, and ROMA values were calculated. Medians of each marker were compared among the three groups. The area under the ROC curve (AUC), sensitivity, and specificity were calculated to analyze the diagnostic performance of each marker. RESULTS: All markers were significantly higher in the malignant group than in the benign group. HE4 levels and ROMA values were significantly higher in the malignant group than in the borderline group. ROMA value had the highest AUC for distinguishing the malignant and borderline groups from the benign group in premenopausal (0.773) and postmenopausal (0.927) patients. CA125 level was significantly higher in patients with endometriosis than in those without (P<0.001), whereas HE4 and CA72-4 levels were not affected by endometriosis (P=0.128 and 0.271, respectively). CONCLUSIONS: ROMA value is the best marker to distinguish malignant and borderline tumors from benign tumors in pre- and postmenopausal patients. HE4 and CA72-4 levels provide information on possible CA125 elevation due to endometriosis.

Effectiveness of adjuvant treatment for morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma: A Korean multicenter study.

AIM: To evaluate the effectiveness of adjuvant treatment for morcellated, uterus-confined leiomyosarcoma in a multicenter setting. METHODS: We identified patients with International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma primarily treated with surgery between 2003 and 2016. Among them, patients who underwent one of the following morcellation methods were included: (i) power morcellation; (ii) intracorporeal morcellation using scalpels or electrocautery; and (iii) vaginal morcellation. Patients' survival outcomes were compared according to the implementation of adjuvant treatment. RESULTS: From 13 institutions, 55 patients were included; 31 for adjuvant treatment group and 24 for surgery only group. The clinicopathological characteristics including the mass size, morcellation methods, extent of surgery, and mitotic count were similar between the groups. In the adjuvant treatment group, 67.7%, 19.4% and 12.9% of patients received chemotherapy, chemoradiation and radiation, respectively. After a median follow-up of 50.5 months, the adjuvant treatment and surgery only groups showed similar overall survival (5-year rate, 92.0% vs 90.4%; P = 0.959). No significant difference in progression-free survival was observed between the two groups (3-year rate, 46.1% vs 78.2%; P = 0.069). On multivariate analyses, adjuvant treatment did not affect progression-free survival (adjusted HR, 2.138; 95% CI, 0.550-8.305; P = 0.273). The adjuvant treatment group showed a trend towards more common distant metastasis, compared to the surgery only group (25.8% vs 4.2%; P = 0.062). The incidences of pelvic, retroperitoneal, and abdominal recurrences were not different between the groups. CONCLUSION: Despite its frequent use in clinical practice, adjuvant treatment did not improve the survival outcomes of patients with morcellated, International Federation of Gynecology and Obstetrics stage I uterine leiomyosarcoma.

Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer.

BACKGROUND: Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis. METHODS: Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy. RESULTS: CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001). CONCLUSIONS: Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.