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

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

Treatment outcomes according to various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia - Multicenter retrospective study (KGOG2033).

OBJECTIVE: To investigate pathologic complete response (pCR) and recurrence outcomes using various progestin treatment strategies in patients with atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN). METHODS: Medical records of patients diagnosed with AH/EIN and undergoing follow-up endometrial biopsy after progestin treatment between 2011 and 2020 were retrospectively reviewed. Clinical factors and treatment outcomes were analyzed according to initial progestin treatment (oral progestin [OP], levonorgestrel-releasing intrauterine device [LNG-IUD], and combination), OP dose, and maintenance treatment using Pearson's χ2, Fisher's exact test, and Kaplan-Meier analysis. RESULTS: Of 124 patients included, 74, 37, and 13 were in the OP, LNG-IUD, and combination groups, respectively. The pCR rate was 79.8% and recurrence rate was 21.2%. The pCR rates within 3 and 6 months were significantly higher in the OP group than in the LNG-IUD group, but were not significantly different within 12 and 24 months. Recurrence rate was significantly higher in the OP group than in the LNG-IUD group. The pCR rate and recurrence rate had no significant differences between the combination group and the other groups. Excluding the LNG-IUD group, 53 and 34 patients received low- and high-dose OP, respectively. The pCR and recurrence rates were comparable between the low- and high-dose OP groups. Maintenance therapy was significantly associated with lower recurrence rate. CONCLUSIONS: Although OP alone achieved more short-term pCR than the other groups, more recurrences occurred after pCR than LNG-IUD alone. High-dose OP as well as combination of OP and LNG-IUD did not increase pCR or reduce recurrence. Maintenance therapy may reduce the recurrence rate after pCR.

Determination of ovarian transposition through prediction of postoperative adjuvant therapy in young patients with early stage cervical cancer undergoing surgery: a Korean multicenter retrospective study (KGOG 1042).

OBJECTIVE: We aimed to predict the risk of postoperative adjuvant therapy using preoperative variables in young patients with early stage cervical cancer. The predicted risk can guide whether ovarian transposition should be performed during surgery. METHODS: In total, 886 patients with stage IB1-IIA cervical cancer aged 20-45 years who underwent modified radical or radical hysterectomy between January 2000 and December 2008 were included. Preoperative variables, preoperative laboratory findings, International Federation of Gynaecology and Obstetrics stage, tumor size, and pathological variables were collected. Patients with high risk factors or those who met the Sedlis criteria were considered adjuvant therapy risk (+); others were considered adjuvant therapy risk (-). A decision-tree model using preoperative variables was constructed to predict the risk of adjuvant therapy. RESULTS: Of 886 patients, 362 were adjuvant therapy risk (+) (40.9%). The decision-tree model with four distinct adjuvant therapy risks using tumor size and age were generated. Specifically, patients with tumor size ≤2.45 cm had low risk (49/367; 13.4%), those with tumor size ≤3.85 cm and >2.45 cm had moderate risk (136/314; 43.3%), those with tumor size >3.85 cm and age ≤39.5 years had high risk (92/109; 84.4%), and those with tumor size >3.85 cm and age >39.5 years had the highest risk (85/96; 88.5%). CONCLUSION: The risk of postoperative adjuvant therapy in young patients with early stage cervical cancer can be predicted using preoperative variables. We can decide whether ovarian transposition should be performed using the predicted risk.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

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.

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.

Initial Experience of Articulating Laparoscopic Instruments for Benign Gynecologic Disease: A Single-Arm Multicenter Prospective Study (Korean Gynecologic Oncology Group 4002).

Laparoscopic surgery has evolved with technological advances in many aspects and increasing demand for its benefits in cosmetics, fast recovery, reduced complication rates and pain. However, it still possesses drawbacks such as limited surgical movement due to the nature of rigid laparoscopic instruments. In order to overcome such limitations, several laparoscopic jointed instruments have been developed. In this prospective multicenter, single-arm cohort study, we investigated the short-term safety and feasibility of the new articulating laparoscopic instruments in benign gynecologic surgery. A total of 113 patients who were diagnosed with benign gynecologic adnexal diseases underwent laparoscopic surgery with articulating laparoscopic instruments. Surgical outcomes, including intra/postoperative complication rates, operation time and estimated blood loss, as well as surgeon's subjective evaluation of the usage of the instruments, were evaluated. The results demonstrated that the articulating laparoscopic instruments had comparable usability and produced similar surgical outcomes to conventional laparoscopic surgery. The objective parameters, such as the operative time and complication rates, as well as the subjective parameters, such as the surgeon's own evaluation of the surgical instruments' usability, demonstrated potential benefits of the instruments in benign gynecological diseases. Overall, the study demonstrated that the use of this novel articulating device is feasible in gynecologic laparoscopic surgery.

Impact of Hormone Replacement Therapy on Risk of Ovarian Cancer in Postmenopausal Women with De Novo Endometriosis or a History of Endometriosis.

The effect of hormone replacement therapy (HRT) on the malignant transformation of postmenopausal endometriosis remains unclear. This study aimed to investigate the impact of HRT on ovarian cancer occurrence in postmenopausal women with de novo endometriosis or a history of endometriosis. A total of 10,304 women that received HRT (the HRT group) and 10,304 that did not (the control group) were selected by 1:1 matching those that met the study criteria. Incidences of ovarian cancer (0.3% in the HRT group and 0.5% in the control group) and cumulative incidence rates of ovarian cancer were similar in the two groups. The overall mean duration of HRT was 1.4 ± 2.2 years, but the duration of HRT in women with ovarian cancer was 2.2 ± 2.9 years. After adjusting for co-variables, receipt of HRT, duration of HRT, combined use of estrogen and progesterone, and tibolone were not found to be risk factors for ovarian cancer. However, the use of estrogen alone was found to be a significant risk factor for ovarian cancer (HR 2.898; 95% CI 1.251-6.715; p = 0.013). With the exception of HRT using estrogen alone, HRT did not increase the risk of ovarian cancer in postmenopausal women with a history of endometriosis or de novo endometriosis.

Postoperative Hormone Replacement Therapy and Survival in Women with Ovarian Cancer.

The effect of postoperative hormone replacement therapy (HRT) on survival in women with ovarian cancer remains unclear. This study aimed to investigate the impact of postoperative HRT on survival in women with ovarian cancer using the nationwide cohort study. Women aged ≤60 and diagnosed with ovarian cancer that received primary surgery were followed-up for 5.6 ± 2.9 years. Mean ages of women administered HRT (the HRT group; n = 263) or not administered HRT (the control group; n = 1521) were 41.5 ± 8.5 and 41.0 ± 11.4 years, respectively. After adjustment for covariables, OS was significantly greater in the HRT group (HR 0.618; 95% CI 0.414−0.922; p = 0.018). Kaplan−Meier curve analysis showed OS was significantly higher in the HRT group (85.3% vs. 76.6%; p = 0.016). The ratio of women with HRT to women without HRT increased significantly with time (restricted mean survival times for OS, p < 0.001). In addition, OS was significantly greater for those that received HRT for >5 years than for those that received HRT for ≤0.5 years (HR 0.234; 95% CI 0.059−0.936; p = 0.040). Postoperative HRT improved survival among women with ovarian cancer. The impact of HRT on survival increased with time and treatment duration.

Bevacizumab versus PARP-inhibitors in women with newly diagnosed ovarian cancer: a network meta-analysis.

BACKGROUND: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis. METHODS: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies. RESULTS: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26). CONCLUSIONS: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab.

Incidence and risk of venous thromboembolism according to primary treatment type in women with endometrial cancer: a population-based study.

BACKGROUND: Current prophylaxes and treatments for venous thromboembolism (VTE) in women with gynecologic cancer are mainly guided by studies on solid cancers because studies in gynecologic cancer did not provide sufficient data. Large-scale studies evaluating the incidence and risk of VTE according to therapeutic modality may guide prophylaxis and treatment of VTE in gynecologic cancer. This study was performed to determine the incidence and risk of VTE according to primary treatment type in Korean women with endometrial cancer. METHODS: We selected 26,256 women newly diagnosed with endometrial cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service database. During the total follow-up period and first six months after primary treatments initiation, the incidence and risk of VTE were evaluated according to primary treatment type, that is, no treatment, surgery, radiotherapy, chemotherapy, or hormone therapy. RESULTS: VTE occurred in 136 per 10,000 women during the total follow-up period and in 54 per 10,000 women during the first six months with the highest frequency in women that underwent chemotherapy. During the first year, the monthly incidence of VTE decreased with time among women that underwent no treatment, surgery, or hormone therapy and remained unchanged in those that received radiotherapy or chemotherapy. Compared with women that received no treatment, VTE risk, especially of PE significantly increased in women that underwent chemotherapy (VTE: hazard ratio (HR), 2.334; 95% CI, 1.38-3.949; P = 0.002) (PE: HR, 2.742; 95% CI, 1.424-5.278; P = 0.003) or hormone therapy (VTE: HR, 2.073; 95% CI, 1.356-3.17; P = 0.001) (PE: HR, 2.086; 95% CI, 1.19-3.657; P = 0.01) during the total follow-up period and women that underwent only chemotherapy during the first six months (VTE: HR, 2.532; 95% CI, 1.291-4.966; P = 0.007) (PE: HR, 3.366; 95% CI, 1.496-7.576; P = 0.003). CONCLUSIONS: In this cohort study, the incidence and risk of VTE were highest in women with endometrial cancer that underwent chemotherapy as a primary treatment. Notably, the incidence of VTE decreased over time in women that received no treatment, surgery, or hormone therapy. This study can help guide therapies for prophylaxis and treatment of VTE in women with endometrial cancer.

Impact of Progesterone on Molecular Mechanisms of Preterm Premature Rupture of Membranes.

The role and mechanisms of progesterone in preterm premature rupture of membranes (PPROM) remains unclear. This study aims to investigate the molecular mechanisms of action of progesterone in pre-labor full-term fetal amniotic membrane cells with and without stimulation by microbial, pro-inflammatory, or thrombogenic agents. Fetal amniotic membranes were collected from 30 women with a normal singleton pregnancy undergoing elective cesarean section at term prior to the onset of labor. The human amniotic epithelial cells isolated were pretreated with and without medroxyprogesterone acetate for 24 h. Then, cells were treated with and without TLR/NLR agonists, pro-inflammatory cytokines, or thrombin for 48 h. Semi-quantitative RT-PCR, Western blot, and caspase-3 activity measurement were performed. Progesterone stimulation decreased the expression of TLR2, TLR5, and Nod2 genes (alone and/or in combination with TLR/NLR agonists) and decreased the expression of IL-1ß and IL-8 genes increased by stimulation with specific agonists for TLR2, TLR4, TLR5, Nod1, and Nod2. Moreover, progesterone decreased thrombin-induced IL-8 gene expression. Progesterone also decreased expression of Bax and Bid proteins (pro-apoptotic factors) increased by stimulation with pro-inflammatory cytokines (TNF-α, NGAL, IL-18, and IL-1ß) and thrombin. Progesterone stimulation alone as well as co-stimulation with TNF-α, NGAL, IL-18, IL-1ß, or thrombin with progesterone either increased, decreased, or did not change the expression of Bcl-2, Bcl-XL, or XIAP genes (anti-apoptotic factors). These data suggest progesterone plays protective roles against PPROM through anti-microbial, anti-inflammatory, and anti-thrombogenic actions on human-term fetal amniotic membrane cells. Progesterone alters pro-inflammatory cytokine- and thrombin-induced apoptosis by controlling the expression of pro-apoptotic and anti-apoptotic factors.

Incidence and risk factors of VTE in patients with cervical cancer using the Korean national health insurance data.

This study investigated incidence and risk factors for venous thromboembolism (VTE) in patients with cervical cancer. We selected 49,514 patients newly diagnosed with cervical cancer from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and first 6 months after initiation of primary treatments, incidence of VTE, and association of risk factors with VTE occurrence were evaluated according to primary treatments or no treatment, surgery, radiotherapy, and chemotherapy. VTE occurred in 1.15% of patients with cervical cancer. Regardless of the period after initiation of primary treatments, and of VTE, the incidence of thromboembolism was highest in chemotherapy. During the first 12 months, monthly incidence of VTE was highest in chemotherapy and decreased with time in all primary treatments. Compared with no treatment, VTE risk significantly increased for all primary treatments (surgery: HR 1.492; 95% CI 1.186-1.877) (radiotherapy: HR 2.275; 95% CI 1.813-2.855) (chemotherapy: HR 4.378; 95% CI 3.095-6.193) and for chemotherapy during the first 6 months (HR 3.394; 95% CI 2.062-5.588). In this cohort study, incidence and risk of VTE in patients with cervical cancer were the highest when chemotherapy was the primary cancer treatment, and incidence of VTE decreased with time.

Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate incidence and risk for venous thromboembolism (VTE) according to primary treatment in women with ovarian cancer. METHODS: We selected 26,863 women newly diagnosed with ovarian cancer between 2009 and 2018 from the Korean Health Insurance Review and Assessment Service databases. During the total follow-up period and the first six months after initiation of primary treatments, incidence and risk of VTE were evaluated according to primary treatment as no treatment, surgery, radiotherapy, or chemotherapy. RESULTS: The mean follow-up period was 1285.5±6 days. The VTE incidence was highest in women who underwent chemotherapy (306 per 10,000 women). Among women who underwent surgery, VTE was highest in surgery with neoadjuvant chemotherapy (536 per 10,000 women), followed by surgery with adjuvant chemotherapy (360 per 10,000 women) and surgery alone (132 per 10,000 women). During the first 12 months, monthly incidence of VTE decreased. Compared with women with no treatment, risk of VTE significantly increased in women undergoing chemotherapy (HR 1.297; 95% CI, 1.08-1.557; P = 0.005) during the total follow-up period and decreased in women undergoing surgery (HR 0.557; 95% CI, 0.401-0.775; P<0.001) and radiotherapy (HR 0.289; 95% CI, 0.119-0.701; P = 0.006) during the first six months. Among women who underwent surgery, VTE risk significantly increased in surgery with neoadjuvant chemotherapy (HR 4.848; 95% CI, 1.86-12.632; P = 0.001) followed by surgery with adjuvant chemotherapy (HR 2.807; 95% CI, 1.757-4.485; P<0.001) compared with surgery alone during the total follow-up period and in surgery with neoadjuvant chemotherapy (HR 4.223; 95% CI, 1.37-13.022; P = 0.012) during the first six months. CONCLUSIONS: In this large Korean cohort study, incidence and risk of VTE were highest in women with ovarian cancer who underwent chemotherapy and surgery with neoadjuvant chemotherapy as a primary cancer treatment. Incidence of VTE decreased over time.

Risk factors of progression to endometrial cancer in women with endometrial hyperplasia: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate risk factors of progression to endometrial cancer (EC) in women with non-atypical and atypical endometrial hyperplasia (EH). METHODS: The data of 62,333 women with EH diagnostic codes from 2007 to 2018 were sourced from the Korean Health Insurance Review and Assessment Service databases. The data from 11,525 women with non-atypical EH and 2,219 women with atypical EH who met the selection criteria were extracted for analysis. RESULTS: Risk of EC in women with EH decreased in 40-49 year olds compared to other ages (non-atypical EH: [≤39 vs. 40-49 years] HR, 0.557; 95% CI, 0.439-0.708; P<0.001; [≤39 vs. ≥50 years] P = 0.739; atypical EH: [≤39 vs. 40-49 years] HR, 0.391; 95% CI, 0.229-0.670; P = 0.001; [≤39 vs. ≥50 years] P = 0.712). Risk of EC increased with increase in number of follow-up biopsies in women with non-atypical EH (1 biopsy: HR, 1.835; 95% CI, 1.282-2.629; P = 0.001; ≥2 biopsies: HR, 3.644; 95% CI, 2.585-5.317; P<0.001) and in women receiving ≥2 follow-up biopsies with atypical EH (HR, 3.827; 95% CI, 1.924-7.612; P = 0.001). Time of progression to EC decreased in women ≥50 years old with non-atypical EH compared to other ages (P = 0.004) and showed no differences among ages in women with atypical EH (P = 0.576). Progestational agents were a protective factor for EC in women with non-atypical EH (HR, 0.703; 95% CI, 0.565-0.876; P = 0.002). CONCLUSIONS: In this claim data analysis, women ≤39 and ≥50 years old with EH were at a high risk for progression to EC, and repeat follow-up biopsy after a diagnosis of EH increased detection of EC. Progestational agents were an effective modality to prevent EC in women with non-atypical EH.

Risk of occult atypical hyperplasia or cancer in women with nonatypical endometrial hyperplasia.

AIM: The aim of this study was to identify subsets of patients diagnosed with nonatypical endometrial hyperplasia (NAEH) by endometrial biopsy who had high risk for occult atypical endometrial hyperplasia (AEH) or endometrial cancer (EC). METHODS: We retrospectively reviewed the medical records of 281 patients who underwent hysterectomy within 6 months after a diagnosis of NAEH. We collected data on age, body mass index, menopausal status, tamoxifen use, previous history of NAEH, details of endometrial biopsy (location, curettage vs. pipelle sampling), NAEH subtype (simple vs. complex), interval between endometrial biopsy and hysterectomy, indication of hysterectomy and the presence of occult AEH or EC in hysterectomy specimen. Associations between variables and occult AEH or EC were analyzed. Risk of occult AEH or EC in subsets were calculated and visualized using a heatmap. RESULTS: Among 281 patients, 34 (12.1%) and 9 (3.2%) had occult AEH and EC in hysterectomy specimens, respectively. Using univariate analysis, we found age, menopausal status and subtype were associated with occult AEH or EC. Using multivariate analysis, older age (odds ratio = 1.09, P < 0.01) and complex subtype (odds ratio = 3.34, P < 0.01) were independent risk factors. Patients at an age ≥ 51 years with complex NAEH had about 50% risk of occult AEH or EC. CONCLUSION: Women at an age ≥ 51 years with complex NAEH had high risk for occult AEH or EC and surgical treatment can be considered for these patients.

Factors encouraging mobile instant messaging service use in medical education.

BACKGROUND: Mobile instant messaging services are being increasingly used for educational purposes, but their effectiveness in medical education is not well known. We assessed whether students' use of Kakao Talk (a mobile instant messaging service) during the early period of a week of clinical education influenced its use for academic purposes during a later period of the same week. METHODS: The online communication records of 151 third-year medical students (in 39 clinical education groups) who used Kakao Talk during clinical education were reviewed. The 39 groups were categorized as low, middle, or high according to the number of total chats (on all subjects, not just academic) per student over five days. The relationship between the number of total chats during the first two days and the number of academic chats during the last three days (of five-day chatroom weeks) was analyzed. RESULTS: The number of total and academic chats over all five days, the first two days, and the last three days was highest in groups with the highest number of total chats per student. Similarly, the highest number of students posting total and academic chats was found in these groups. In addition, the number of academic chats per student and the frequency of questions raised by students were also highest in these groups. During the last three days, the number of students posting total chats was lower than that during the first two days, and the number of academic chats per student posting academic chats was higher. The number of total chats on the first or second day positively correlated with the maximum value of academic chats on the third to fifth days. CONCLUSION: High frequency mobile instant messaging use early on in clinical education might encourage its use for academic purposes during later periods.

Outcomes of non-high grade serous carcinoma after neoadjuvant chemotherapy for advanced-stage ovarian cancer: a Korean gynecologic oncology group study (OV 1708).

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.

Impact of hospital care volume on clinical outcomes of laparoscopic radical hysterectomy for cervical cancer: A systematic review and meta-analysis.

BACKGROUND: In cervical cancer, the impact of hospital volume of laparoscopic radical hysterectomy (LRH) has not been investigated systematically as in ovarian cancer.The aim of this study was to investigate the impact of hospital care volume of LRH on treatment outcomes of patients with cervical cancer. METHODS: The PubMed, Embase, and Cochrane Library databases were searched with the terms "cervical cancer," "radical hysterectomy," and "laparoscopy." The selection criteria included studies presenting operative outcomes and/or perioperative complications of LRH from high-volume hospitals (HVHs) (≥15 cases/year) and low-volume hospitals (LVHs) (<15 cases/year). Fifty-nine studies including 4367 cases were selected. Linear regression analysis weighted by the average annual case number in each study was performed to evaluate differences between the groups. RESULTS: In HVH, a higher number of lymph nodes (24.5 vs 21.1; P = .037) were retrieved by LRH in older women (48.4 vs 44.5 years; P = .010) with tendencies of shorter operation time (224.4 vs 256.4 minutes; P = .096) and less blood loss (253.1 vs 322.2 mL; P = .080). Compared with LVH, HVH had fewer patients with stage IA disease (13.8 vs 24.4%; P = .003) and more patients with stage IIA disease (15.3 vs 7.1%; P = .052) with comparable 5-year overall survival (93.1 vs 88.6%; P = .112). CONCLUSION: HVH is a prognostic factor for operative outcome and perioperative complications in patients with cervical cancer undergoing LRH. The exact effect of hospital volume on survival outcome needs to be evaluated.

Relationship between threatened miscarriage and gestational diabetes mellitus.

BACKGROUND: Both threatened miscarriage and gestational diabetes mellitus (GDM) are common complications of pregnancy. However, only one pilot study has reported that these complications are not related. We aimed to investigate whether threatened miscarriage is one of the risk factors of GDM. METHODS: An unmatched case-control study of 1567 pregnant Korean women who underwent a two-step approach to diagnose GDM was retrospectively conducted. The eligible women were classified into normal (n = 840), borderline GDM (n = 480), and GDM (n = 247) groups. We analyzed the associations with threatened miscarriage in all groups with adjustment for confounding factors. RESULTS: The proportion of women who experienced threatened miscarriage was significantly lower in the GDM group than in the normal group (adjusted odds ratio (OR), 0.38; 95% confidence interval (CI), 0.18-0.78). It was significantly lower in the maternal hyperglycemia group (borderline GDM and GDM groups) than in the normal group (adjusted OR, 0.66; 95% CI, 0.47-0.91). The proportion of women who experienced threatened miscarriage was also significantly lower in the GDM group than in the normal (adjusted OR, 0.35; 95% CI, 0.17-0.70) and borderline GDM groups (adjusted OR, 0.46; 95% CI, 0.22-0.94). Moreover, the proportion of women who experienced threatened miscarriage significantly decreased according to the severity of glucose intolerance (adjusted OR, 0.94; 95% CI, 0.76-1.16). CONCLUSION: This study demonstrates that threatened miscarriage is associated with decreased risk of GDM and the severity of glucose intolerance in Korean women. Additional studies are warranted to understand the pathophysiologic mechanisms that might exist between these frequent complications of pregnancy.