Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer. @*Materials and Methods@#This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m2 Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m2 Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m2 Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort. @*Results@#Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m2 of Genexol-PM in combination with AUC 5-6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%. @*Conclusion@#Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer pati-ents. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m2 when combined with carboplatin.

Robot-Assisted Laparoscopic Myomectomy versus Abdominal Myomectomy for Large Myomas Sized over 10 cm or Weighing 250 g

Purpose@#Here, we compared the operative and perioperative outcomes between robot-assisted laparoscopic myomectomy (RALM) and abdominal myomectomy (AM) in patients with large (>10 cm) or heavy myomas (>250 g). @*Materials and Methods@#We included 278 patients who underwent multi-port RALM (n=126) or AM (n=151) for large or heavy myomas in a tertiary care hospital between April 2019 and June 2020. The t-test, chi-square, Bonferroni’s test, and multiple linear regression were used. @*Results@#No differences were observed in age, body mass index, parity, or history of pelvic surgery between the two groups. Myoma diameters were not different (10.8±2.52 cm vs. 11.2±3.0 cm, p=0.233), but myomas were lighter in the RALM group than in the AM group (444.6±283.14 g vs. 604.68±368.35 g, respectively, p=0.001). The RALM group had a higher proportion of subserosal myomas, fewer myomas, fewer large myomas over >3 cm, lighter myomas, and longer total operating time. However, the RALM group also had shorter hospital stay and fewer short-term complications. Estimated blood loss (EBL) was not different between the two groups. The number of removed myomas was the most significant factor (coefficient=10.89, p<0.0001) affecting the EBL. @*Conclusion@#RALM is a feasible myomectomy technique even for large or heavy myomas. RALM patients tend to have shorter hospital stays and fewer postoperative fevers within 48 hours. However, RALM has longer total operating time.

Feasibility and safety of fertilitysparing surgery in epithelial ovarian cancer with dense adhesion: a longterm result from a single institution / 부인종양

Objective@#We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions. @*Methods@#Patients were divided into cases with and without dense adhesions in this retrospective study. @*Results@#Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4–230.0) months. There were no differences in the rates of recurrence (21.2% vs.20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3–2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1–1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into nontumor and tumor associated dense adhesions for further analysis and the results were same. @*Conclusion@#FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

Feasibility and safety of fertilitysparing surgery in epithelial ovarian cancer with dense adhesion: a longterm result from a single institution / 부인종양

Objective@#We investigated the feasibility and safety of fertility-sparing surgery (FSS) in patients with epithelial ovarian cancer (EOC) with dense adhesions. @*Methods@#Patients were divided into cases with and without dense adhesions in this retrospective study. @*Results@#Of the 95 eligible patients, 29 patients had dense adhesions. Mean age, proportion of staging procedure, distribution of histologic type, and co-presence of endometriosis were different (p=0.003, 0.033, 0.011, and 0.011, respectively). The median follow-up period was 57.8 (0.4–230.0) months. There were no differences in the rates of recurrence (21.2% vs.20.7%, p=1.000) or death (16.7% vs. 6.9%, p=0.332) between the 2 groups. There was no difference in the pattern of recurrence or in disease-free survival (DFS) and overall survival (OS) between the 2 groups. In multivariate analysis, pretreatment cancer antigen-125 >35 U/mL and International Federation of Gynecology and Obstetrics stage IC were significant factors of worse DFS and OS, while dense adhesion was not a prognostic factor for both DFS (hazard ratio [HR]=0.9; 95% confidence interval [CI]=0.3–2.7; p=0.792) and OS (HR=0.2; 95% CI=0.1–1.8; p=0.142), nor were age, proportion of staging procedure, histologic type, and co-presence of endometriosis. Moreover, the distribution of those 2 significant prognostic factors was not different between the 2 groups. Dense adhesions were subgrouped into nontumor and tumor associated dense adhesions for further analysis and the results were same. @*Conclusion@#FSS is feasible and safe in EOC, regardless of the presence of dense adhesions.

Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

Endometrial thickness cut-off value by transvaginal ultrasonography for screening of endometrial pathology in premenopausal and postmenopausal women

OBJECTIVE: To assess the clinical usefulness and diagnostic accuracy of ultrasonographic measurement of endometrial thickness (ET) in women with endometrial hyperplasia or cancer (EH+). METHODS: This retrospective cohort study included 29,995 consecutive women who underwent transvaginal ultrasonography (TVS) for an incidental finding of a thickened endometrium at the health screening and promotion center at Asan Medical Center between 2006 and 2010. Among 959 patients with endometrial abnormalities, 92 patients were included in this study. A total of 867 patients were excluded: 416 were lost to follow-up; 263 did not undergo endometrial biopsy; 155 had endometrial polyps; 17 had submucosal myomas; and 16 had insufficient tissue samples. Endometrial histology was the reference standard for calculating accuracy. RESULTS: Of the 92 patients, 78 (84.8%) had normal pathology, while 14 (15.2%) had endometrial pathology (EH+), including 5 patients (35.7%) with simple hyperplasia without atypia, 3 (21.4%) with complex hyperplasia, and 6 (42.9%) with endometrial carcinoma, all stage Ia. The area under the receiver-operating characteristic curve was 0.75 (95% confidence interval [CI], 0.593–0.906). The cut-off value for ET was 8 mm, indicating that TVS ET had a fair accuracy in diagnosing carcinoma, had a sensitivity of 100% (95% CI, 62.9–100.0%) and a specificity of 24.3% (95% CI, 15.2–36.3%). CONCLUSION: TVS is useful for detecting EH+, with a cut-off value for ET of 8 mm having a high sensitivity for detecting endometrial pathologies and the ability to identify women highly unlikely to have EH+, thereby avoiding more invasive endometrial biopsy.

Erratum: Correction of Acknowledgements

The Acknowledgements was published incorrectly.

Hypoxic Preconditioned Mesenchymal Stromal Cell Therapy in a Rat Model of Renal Ischemia-reperfusion Injury: Development of Optimal Protocol to Potentiate Therapeutic Efficacy

Although previous and ongoing clinical studies have used stromal cells during renal ischemia-reperfusion injury (IRI), there is little consensus regarding the optimal protocol. We aimed to optimize the protocol for hypoxic preconditioned human bone marrow-derived mesenchymal stromal cell (HP-hBMSC) therapy in a rat model of renal IRI. We determined the optimal injection route (renal arterial, renal parenchymal, and tail venous injection), dose (low-dose: 1×10⁶, moderate-dose: 2×10⁶, and high-dose: 4×10⁶), and injection period (pre-, concurrent-, and post-IRI). During optimal injection route study, renal arterial injections significantly reduced the decreasing glomerular filtration rate (GFR), as compared to GFRs for the IRI control group, 2 and 4 days after IRI. Therapeutic effects and histological recoveries were the greatest in the group receiving renal arterial injections. During the dose finding study, high-dose injections significantly reduced the decreasing GFR, as compared to GFRs for the IRI control group, 3 days after IRI. Therapeutic effects and histological recoveries were the greatest in the high-dose injection group. While determining the optimal injection timing study, concurrent-IRI injection reduced elevated serum creatinine levels, as compared to those of the IRI control group, 1 day after IRI. Pre-IRI injection significantly reduced the decreasing GFR, as compared with GFRs for the IRI control group, 1 day after IRI. Therapeutic effects and histological recoveries were the greatest in the concurrent-IRI group. In conclusion, the concurrent-IRI administration of a high dose of HP-hBMSC via the renal artery leads to an optimal recovery of renal function after renal IRI.

Optimization to detect TP53 mutations in circulating cell-free tumor DNA from patients with serous epithelial ovarian cancer

OBJECTIVE: Circulating cell-free tumor DNA (cfDNA) is the DNA released by apoptotic and necrotic cells of the primary tumor into the blood during the period of tumor development. The cfDNA reflects the genetic and epigenetic alterations of the original tumor. TP53 mutations are a defining feature of high-grade serous ovarian carcinoma. We optimized the methods for detecting TP53 mutations in cfDNA from blood samples. We confirmed the correlation of TP53 mutation in primary ovarian cancer tissue and it in cfDNA using digital polymerase chain reaction (dPCR). METHODS: We found 12 frequent mutation sites in TP53 using The Cancer Genome Atlas and Catalogue of Somatic Mutations in Cancer data and manufactured 12 primers. The mutations in tissues were evaluated in fresh-frozen tissue (FFT) and formalin-fixed paraffin-embedded tissue (FFPET). We performed a prospective analysis of serial plasma samples collected from 4 patients before debulking surgery. We extracted cfDNA and calculated its concentration in blood. dPCR was used to analyze TP53 mutations in cfDNA, and we compared TP53 mutations in ovarian cancer tissue with those in cfDNA. RESULTS: Ten primers out of 12 detected the presence of TP53 mutations in FFT, FFPET, and cfDNA. In FFT and FFPET tissue, there were no significant differences. The average cfDNA concentration was 2.12±0.59 ng/mL. We also confirmed that mutations of cfDNA and those of FFT were all in R282W site. CONCLUSION: This study developed detection methods for TP53 mutations in cfDNA in ovarian cancer patients using dPCR. The results demonstrated that there are the same TP53 mutations in both ovarian cancer tissue and cfDNA.

Diagnostic value of integrated ¹⁸F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in recurrent epithelial ovarian cancer: accuracy of patient selection for secondary cytoreduction in 134 patients / 부인종양

OBJECTIVE: The aim of this study was to evaluate the diagnostic value of integrated 18F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) for suspected recurrence of epithelial ovarian cancer (EOC) with non-disseminated lesions. METHODS: We retrospectively reviewed the medical records of recurrent EOC patients who underwent secondary cytoreduction from January 2000 to December 2013. A total of 134 patients underwent secondary cytoreduction after imaging with either 18F-FDG-PET/CT or contrast-enhanced computed tomography (CECT). RESULTS: In a patient-based analysis of 134 patients, 124 (92.5%) were confirmed to be positive for malignancy. Among 72 patients with suspected non-disseminated recurrence on 18F-FDG-PET/CT, 65 (89.0%) were confirmed to have recurrence, giving 98.5% sensitivity, 87.7% accuracy, and 88.9% positive predictive value (PPV). In the 65 patients with recurrence, residual tumor remained in 14 patients, giving an accuracy of patient selection for secondary cytoreduction of 69.4% (50/72) and it is higher than that of CECT (64.0%). In 169 lesions removed from patients who underwent preoperative 18F-FDG-PET/CT, 135 (79.9%) were confirmed to be positive for malignancy and 124 were accurately detected by 18F-FDG-PET/CT, giving 91.9% sensitivity, 81.1% accuracy, and 85.5% PPV. Foreign body granuloma was found in 33.3% of 21 lesions with false-positive 18F-FDG-PET/CT findings (7/21). The mean preoperative cancer antigen 125 (CA-125) level in false-positive patients was 28.8 U/mL. CONCLUSION: Compared with CECT, 18F-FDG-PET/CT shows higher sensitivity in lesion-based analysis and better accuracy of patient selection for secondary cytoreduction. However, there is still a need for integration of the results of 18F-FDG-PET/CT, CECT, and CA-125 levels to aid treatment planning.

Androgen receptor as a prognostic biomarker and therapeutic target in uterine leiomyosarcoma / 부인종양

OBJECTIVE: To investigate the expression of androgen receptor (AR) and its correlation with disease status and survival outcome in uterine leiomyosarcoma with other hormone receptors. METHODS: The medical records and paraffin blocks of 42 patients were reviewed. The immunohistochemical expression of AR, estrogen receptor (ER), progesterone receptor (PR), gonadotropin releasing hormone (GnRH), and cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) were assessed using tissue microarray. RESULTS: In total, AR expression was observed in 11 patients (26.2%). International Federation of Gynecology and Obstetrics (FIGO) stage and AR were independent factors for disease-free survival (DFS) in multivariate regression analysis (odds ratio [OR]=5.8; 95% confidence interval [CI]=1.2–28.4 and OR=0.2; 95% CI=0.05–0.90; p=0.029 and 0.032, respectively). There were no deaths in the AR expression group, whereas the 5-year overall survival (OS) was 54.8% in the no expression group (p=0.014). Co-expression of ER and/or PR with AR was associated with significantly better 5-year DFS and OS than those with negative AR (72.7% vs. 28.6% and 100% vs. 64.3%; p=0.020 and 0.036, respectively). AR may be an independent prognostic marker regardless of ER/PR. CONCLUSION: AR can be a potential prognostic biomarker in uterine leiomyosarcoma.

Current medical treatment of uterine fibroids

Uterine fibroids (leiomyomas or myomas), benign monoclonal tumors, are the most common benign tumors in women. Heavy or prolonged menstrual bleeding, abnormal uterine bleeding, resultant anemia, pelvic pain, infertility, and/or recurrent pregnancy loss are generally associated with uterine fibroids. Although curative treatment of this tumor relies on surgical therapies, medical treatments are considered the first-line treatment to preserve fertility and avoid or delay surgery. The aim of this review is to provide available and emerging medical treatment options for symptomatic uterine fibroids. Literature review and consensus of expert opinion. Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow-up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Treatment options for symptomatic uterine fibroids — include medical, surgical, and radiologically guided interventions. Various medical therapies are now available for women with uterine fibroids, although each therapy has its own advantages and disadvantages. Currently, gonadotrophin-releasing hormone (GnRH) agonists and selective progesterone receptor modulators (SPRMs) are the most effective medical therapies, with the most evidence to support their reduction of fibroid volume and symptomatic improvement in menstrual bleeding. The choice of treatment depends on the patient's personal treatment goals, as well as efficacy and need for repeated interventions.

Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease / 부인종양

OBJECTIVE: The aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D). METHODS: We conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors. RESULTS: The complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant. CONCLUSION: Based on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment.

An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016) / 부인종양

OBJECTIVE: This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. METHODS: This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40–75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. RESULTS: In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. CONCLUSION: Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.

Prognostic value of metabolic parameters determined by preoperative ¹⁸F-FDG PET/CT in patients with uterine carcinosarcoma / 부인종양

OBJECTIVE: To evaluate the prognostic value of metabolic parameters measured by preoperative ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in patients with uterine carcinosarcoma (UCS). METHODS: Data of 55 eligible patients with UCS who underwent preoperative ¹⁸F-FDG PET/CT and surgical staging were analyzed retrospectively. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV₂.₅), and total lesion glycolysis (TLG₂.₅) of the primary tumors were measured using a SUV threshold of 2.5. The optimal cutoff value of each parameter was determined by time-dependent receiver operating characteristic curve, and its impact on progression-free survival and overall survival was evaluated by Cox proportional hazards model. RESULTS: During a median follow-up period of 29 (range, 1.5–109.4) months, 47.3% (26/55) of the patients experienced disease progression, and the disease-associated mortality rate was 43.6% (24/55). Univariate analysis determined that hazard ratios (HRs) for disease progression for SUVmax (≥8.33), MTV₂.₅ (≥63.92 mL), and TLG₂.₅ (≥396.16) were 1.930 (95% confidence interval [CI]=0.793–4.701), 3.264 (95% CI=1.466–7.268), and 2.692 (95% CI=1.224–5.924), respectively. And, HRs for death were 1.979 (95% CI=0.774–5.060), 2.764 (95% CI=1.217–6.274), and 2.721 (95% CI=1.198–6.182), respectively. While peritoneal cytology, histology, and tumor diameter were independent prognostic factors in multivariate analysis, MTV and TLG were not. CONCLUSION: Though MTV and TLG of primary UCS were not independent predictors compared to surgically obtained data, MTV and TLG of primary UCS may provide useful information on prognosis especially in patients who are not able to undergo surgical staging.

Erratum: Author correction

The Editorial Office of Obstet Gynecol Sci would like to correct the author list.

The efficacy and safety of pegylated liposomal doxorubicin monotherapy and combination therapy with carboplatin in Korean patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer: a single-institution experience

OBJECTIVE: This study aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) with or without carboplatin in Korean patients with recurrent ovarian cancer (ROC), fallopian tube, or primary peritoneal cancer. METHODS: This retrospective study included 52 patients with ROC, fallopian tube, or primary peritoneal cancer who received PLD (50 mg/m²) between 1(st) December 2014 and 31(th) July 2016. RESULTS: The mean number of chemotherapy cycles was 3.8 (range, 2 to 9) in the PLD monotherapy group and 7 (range, 2 to 13) in the PLD combined with carboplatin (PLD-C) group. In overall response rates and clinical beneficial rates, PLD monotherapy group shows 5.0% and 17.5%, and PLD-C group shows 33.3% and 75.0%. The mean progression-free survival (PFS) was 5 and 13 months in the PLD monotherapy and PLD-C groups, respectively. At 6 months after treatment initiation, absence of disease progression was confirmed in 6 (15%) and 10 (83.3%) patients in the PLD monotherapy and PLD-C groups. Hematological adverse events (e.g., neutropenia and thrombocytopenia) were more common in the PLD-C group (P<0.001, P=0.004). The incidence of anemia and non-hematological adverse events, including mucositis, hand-foot syndrome, and allergic reactions, was similar in both groups. CONCLUSION: This study demonstrated the efficacy and safety of PLD monotherapy and PLD-C combination in Korean patients with ROC. This study would be helpful to consider the degree of worry about side effects and treatment expectations after treatment. Further retrospective studies with larger samples are required to confirm the efficacy of PLD monotherapy in Asian patients with platinum-resistant ROC.

Pathologic findings at risk-reducing salpingo-oophorectomy (RRSO) in germline BRCA mutation carriers with breast cancer: significance of bilateral RRSO at the optimal age in germline BRCA mutation carriers / 부인종양

OBJECTIVE: Most BRCA1/2 carriers do not undergo risk-reducing salpingo-oophorectomy (RRSO) by the recommended age. This study aimed to find the incidence of precursor lesions and cancer after RRSO. METHODS: We retrospectively reviewed breast cancer patients identified as BRCA mutation carriers who underwent RRSO at Asan Medical Center, Seoul, Korea, from 2010 to 2014. From 2013, all cases were examined according to the Sectioning and Extensively Examining the Fimbria (SEE/FIM) protocol and underwent immunohistochemically staining. RRSO was performed in 63 patients, 27 in 2010 to 2012 and 36 in 2013 to 2014. RESULTS: The median age at RRSO was 46.5 years (range, 32 to 73 years). Occult invasive cancer was detected in eight patients, of ovarian origin in five and of tubal origin in three. All occult invasive cancer cases with metastasis were detected in patients older than 40 years. Of the 36 patients from the 2013 to 2014 cohort, seven showed p53 overexpression, one showed Ki-67 overexpression, two showed serous tubal intraepithelial carcinoma, and three showed occult cancer. The detection rate of precursor lesions or cancer was 36.1% (13/36). In the analysis according to age, precursor lesions were more common in BRCA1 mutation carriers younger than 40 years old (66.7% vs. 20.0%). In BRCA2 mutation carriers, precursor lesions were only detected in those older than 40 years of age, indicating the possible faster occurrence of precursor lesions in BRCA1 mutation carriers. CONCLUSION: Many patients still tend to delay RRSO until after they are 40 years old. Our findings support the significance of RRSO before the age of 40 in germline BRCA mutation carriers.

The Effect of Breastfeeding Duration and Parity on the Risk of Epithelial Ovarian Cancer: A Systematic Review and Meta-analysis / 예방의학회지

OBJECTIVES: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). METHODS: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Thirty-two studies had parity categories of 1, 2, and ≥3. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p=0.17; Q=18.79, I²=25.5%). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. CONCLUSIONS: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.

Treatment of uterine leiomyoma: how to choose a therapeutic method?

Uterine leiomyomas (myomas or fibroids) are the most common benign pelvic tumors in reproductive aged women occurring in 25% to 40%. They may cause symptoms of heavy or prolonged menstrual bleeding, pelvic pressure symptoms and pain, subfertility, adverse pregnancy outcomes. Therapeutic methods are variable and include expectant management, medical treatment (GnRH agonist, levonorgestrel-releasing intrauterine system, and progesterone receptor modulator), surgical treatment (myomectomy, hysterectomy, and endometrial ablation), myolysis, and uterine artery embolization. Most women who are asymptomatic or have mild symptoms can be followed without intervention. In cases with significant symptoms, the clinicians should understand many factors including age, parity, proximity to menopause, desire for fertility preservation, size, location and number of myomas, severity of symptoms and possibility of malignancy for the choice of treatment modality. The type and timing of the intervention should be individualized after considering and discussing treatment benefit and risk.