Publications by authors named "Se Ik Kim"

54 Publications

Prognostic implications of body composition change during primary treatment in patients with ovarian cancer: A retrospective study using an artificial intelligence-based volumetric technique.

Gynecol Oncol 2021 May 13. Epub 2021 May 13.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address:

Objective: To investigate the impact of changes in body composition during primary treatment on survival outcomes in patients with epithelial ovarian cancer (EOC).

Methods: We retrospectively identified patients diagnosed with EOC between 2010 and 2019. Using an artificial intelligence-based tool, the volumes of skeletal muscle, visceral fat, and subcutaneous fat were measured automatically at the waist level from pre-treatment and post-treatment computed tomography scans. Associations between changes in body mass index (BMI) and volume of each body composition component and survival outcomes were evaluated.

Results: A total of 208 patients were included. A significant decrease in BMI and waist volumes of skeletal muscle and visceral fat was observed during the primary treatment. Patients with BMI loss ≥5% showed significantly worse progression-free survival (PFS) and overall survival (OS) than those with BMI loss <5%. In multivariate analyses adjusting for clinicopathologic factors, BMI loss ≥5% was identified as an independent poor prognostic factor for PFS (adjusted HR, 1.565; 95% CI, 1.074-2.280; P = 0.020) and OS (adjusted HR, 2.754; 95% CI, 1.382-5.488; P = 0.004). Meanwhile, both muscle loss ≥10% and visceral fat loss ≥20% were associated with an increased mortality rate but did not affect disease recurrence. In multivariate analyses, muscle loss ≥10% (adjusted HR, 2.069; 95% CI, 1.055-4.058; P = 0.034) and visceral fat loss ≥20% (adjusted HR, 2.292; 95% CI, 1.023-5.133; P = 0.044) were poor prognostic factors for OS. Consistent results were observed in the advanced-stage disease subgroup (n = 173).

Conclusions: Changes in BMI and waist volume of skeletal muscle and visceral fat were associated with survival outcomes in patients with EOC.
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http://dx.doi.org/10.1016/j.ygyno.2021.05.004DOI Listing
May 2021

Uterine serous carcinoma.

Gynecol Oncol 2021 Apr 29. Epub 2021 Apr 29.

Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.
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http://dx.doi.org/10.1016/j.ygyno.2021.04.029DOI Listing
April 2021

Development of Machine Learning Models to Predict Platinum Sensitivity of High-Grade Serous Ovarian Carcinoma.

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

To support the implementation of individualized disease management, we aimed to develop machine learning models predicting platinum sensitivity in patients with high-grade serous ovarian carcinoma (HGSOC). We reviewed the medical records of 1002 eligible patients. Patients' clinicopathologic characteristics, surgical findings, details of chemotherapy, treatment response, and survival outcomes were collected. Using the stepwise selection method, based on the area under the receiver operating characteristic curve (AUC) values, six variables associated with platinum sensitivity were selected: age, initial serum CA-125 levels, neoadjuvant chemotherapy, pelvic lymph node status, involvement of pelvic tissue other than the uterus and tubes, and involvement of the small bowel and mesentery. Based on these variables, predictive models were constructed using four machine learning algorithms, logistic regression (LR), random forest, support vector machine, and deep neural network; the model performance was evaluated with the five-fold cross-validation method. The LR-based model performed best at identifying platinum-resistant cases with an AUC of 0.741. Adding the FIGO stage and residual tumor size after debulking surgery did not improve model performance. Based on the six-variable LR model, we also developed a web-based nomogram. The presented models may be useful in clinical practice and research.
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http://dx.doi.org/10.3390/cancers13081875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070756PMC
April 2021

Increasing serum gamma-glutamyltransferase level accompanies a rapid increase in the incidence of endometrial cancer in Korea: A nationwide cohort study.

Gynecol Oncol 2021 Jun 29;161(3):864-870. Epub 2021 Mar 29.

Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea; WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea; Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address:

Objective: This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis.

Methods: We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588).

Results: Obese (BMI, ≥25 kg/m) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227).

Conclusions: Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.
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http://dx.doi.org/10.1016/j.ygyno.2021.03.024DOI Listing
June 2021

Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.

Mol Carcinog 2021 05 15;60(5):297-312. Epub 2021 Mar 15.

Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.
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http://dx.doi.org/10.1002/mc.23289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080545PMC
May 2021

Post-LACC era: critical assessment not "all-or-none" is needed.

J Gynecol Oncol 2021 Mar;32(2):e47

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

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http://dx.doi.org/10.3802/jgo.2021.32.e47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930447PMC
March 2021

Lymph Node Ratio Is a Strong Prognostic Factor in Patients with Early-Stage Cervical Cancer Undergoing Minimally Invasive Radical Hysterectomy.

Yonsei Med J 2021 Mar;62(3):231-239

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

Purpose: To determine whether the prognostic impact of lymph node ratio (LNR), defined as the ratio between the number of positive lymph nodes and removed lymph nodes, differs between open and minimally invasive surgical approaches for radical hysterectomy (RH) in node-positive, early-stage cervical cancer.

Materials And Methods: We retrospectively identified 2009 International Federation of Gynecology and Obstetrics stage IB1-IIA2 patients who underwent primary type C RH between 2010 and 2018. Among them, only those with pathologically proven lymph node metastases who received adjuvant radiation therapy were included. The prognostic significance of LNR was investigated according to open surgery and minimally invasive surgery (MIS).

Results: In total, 55 patients were included. The median LNR (%) was 9.524 (range, 2.083-62.500). Based on receiver operating characteristic curve analysis, the cut-off value for LNR (%) was determined as 8.831. Overall, patients with high LNR (≥8.831%; n=29) showed worse disease-free survival (DFS) than those with low LNR (<8.831%, n=26) (=0.027), whereas no difference in overall survival was observed. Multivariate analyses adjusting for clinicopathologic factors revealed that DFS was adversely affected by both MIS [adjusted hazard ratio (HR), 8.132; =0.038] and high LNR (adjusted HR, 10.837; =0.045). In a subgroup of open surgery cases, LNR was not associated with disease recurrence. However, in a subgroup of MIS cases, high LNR was identified as an independent poor prognostic factor for DFS (adjusted HR, 14.578; =0.034).

Conclusion: In patients with node-positive, early-stage cervical cancer, high LNR was associated with a significantly higher disease recurrence rate. This relationship was further consolidated among patients who received MIS RH.
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http://dx.doi.org/10.3349/ymj.2021.62.3.231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934101PMC
March 2021

Endometrial Cancer.

N Engl J Med 2021 02;384(6):586

Seoul National University College of Medicine, Seoul, South Korea

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http://dx.doi.org/10.1056/NEJMc2035378DOI Listing
February 2021

Pregnancy Outcomes in Female Patients with Alopecia Areata: A Nationwide Population-Based Study.

J Invest Dermatol 2021 Jan 8. Epub 2021 Jan 8.

Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea; Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea; Institute of Human-Environment Interface Biology, Seoul National University College of Medicine, Seoul, Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2020.12.014DOI Listing
January 2021

Survival impact of extended cycles of second-line chemotherapy in platinum-sensitive relapsed ovarian cancer patients with residual tumor after six cycles.

BMC Cancer 2020 Dec 7;20(1):1199. Epub 2020 Dec 7.

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea.

Background: To determine if extended chemotherapy improves survival outcomes in patients with platinum-sensitive relapsed epithelial ovarian cancer (EOC) who have residual disease after six cycles of second-line chemotherapy.

Methods: In this study, 135 EOC patients who experienced platinum-sensitive recurrence after primary treatment between 2008 and 2018, and had a residual tumor ≥0.5 cm (detected on CT scans) after completing six cycles of second-line, platinum-based chemotherapy, were retrospectively reviewed. Based on the number of main therapy cycles (second-line chemotherapy), we divided patients into an extended group (>6 cycles, n = 52) or a standard group (6 cycles, n = 83) and compared patient characteristics and survival outcomes between these groups.

Results: The extended group had a shorter platinum-free interval after primary treatment than the standard group (median, 11.0 vs. 13.1 months; P = 0.018). Secondary debulking surgery was less frequently performed in the standard group (1.9% vs. 19.3%; P = 0.003). After six chemotherapy cycles, the extended and standard groups showed similar serum CA-125 levels (P = 0.122) and residual tumor sizes (P = 0.232). There was no difference in overall survival (OS) between the groups (P = 0.382), although the extended group had significantly worse progression-free survival (PFS) than the standard group (median, 13.9 vs. 15.1 months; P = 0.012). Multivariate analyses revealed that platinum-free interval was an independent prognostic factor for PFS and OS, but extended chemotherapy was not (PFS: HR, 1.25; 95% CI, 0.84-1.85; P = 0.279; and OS: HR, 1.36; 95% CI, 0.72-2.56; P = 0.342). We observed consistent results in the subset of patients who did not undergo secondary debulking surgery.

Conclusions: More than six cycles of platinum-based chemotherapy might not improve survival outcomes in patients with platinum-sensitive recurrent EOC who had a residual tumor ≥0.5 cm after six cycles of second-line chemotherapy.
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http://dx.doi.org/10.1186/s12885-020-07658-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720565PMC
December 2020

Impact of Adjuvant Radiotherapy on Survival Outcomes in Intermediate-Risk, Early-Stage Cervical Cancer: Analyses Regarding Surgical Approach of Radical Hysterectomy.

J Clin Med 2020 Nov 3;9(11). Epub 2020 Nov 3.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

This study aimed to investigate the impact of adjuvant radiotherapy (RT) on survival outcomes in patients with intermediate-risk, early-stage cervical cancer who underwent radical hysterectomy (RH). From the cervical cancer cohorts of two tertiary hospitals, patients with 2009 FIGO stage IB-IIA who underwent primary RH between 2010 and 2018 were identified. Patients with intermediate-risk factors that met the Sedlis criteria were included. Survival outcomes were compared between the patients who received adjuvant RT (study group; = 53) and those who did not receive adjuvant treatment (control group; = 30). Compared to the control group, the study group showed significantly better recurrence-free survival (RFS; 5-year survival rate, 85.6% vs. 61.0%; = 0.009). In multivariate analysis, adjuvant RT was associated with a significantly lower risk of disease recurrence (adjusted HR, 0.241; 95% CI, 0.082-0.709; = 0.010). In a subgroup that underwent open RH ( = 33), adjuvant RT showed a trend toward improved RFS with borderline statistical significance (adjusted HR, 0.098; 95% CI, 0.009-1.027; = 0.053). However, in a subgroup of minimally invasive surgery ( = 50), adjuvant RT did not improve RFS. In conclusion, implementation of adjuvant RT significantly reduced the disease recurrence rate in patients with intermediate-risk, stage IB-IIA cervical cancer treated primarily with surgery. Survival benefit from adjuvant RT differed according to the surgical approach.
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http://dx.doi.org/10.3390/jcm9113545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692216PMC
November 2020

Recurrence patterns after bevacizumab in platinum-sensitive, recurrent epithelial ovarian cancer.

Int J Gynecol Cancer 2020 12 14;30(12):1943-1950. Epub 2020 Oct 14.

Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea (the Republic of)

Objective: Evidence on recurrence patterns after bevacizumab in epithelial ovarian cancer is still insufficient. The aim of this study was to evaluate recurrence patterns after treatment with bevacizumab as second-line treatment in patients with platinum-sensitive, recurrent epithelial ovarian cancer.

Methods: We retrospectively identified epithelial ovarian cancer patients who relapsed ≥6 months after primary treatment consisting of surgery and platinum-based chemotherapy between January 2008 and June 2019. Only those who received platinum-based doublet chemotherapy with bevacizumab or without bevacizumab as second-line treatment were included (n=192). To adjust confounders, we conducted 1:2 propensity score matching for platinum-free interval and secondary debulking surgery. Imaging studies were performed to locate newly developed or enlarged pre-existing tumors. Recurrence patterns were compared between bevacizumab users (study group) and non-users (control group).

Results: After matching, the study group (n=52) and control group (n=104) showed similar baseline clinicopathologic characteristics including platinum-free interval (median (range) 15.3 (6.2-87.3) vs 14.0 (6.2-143.5) months; p=0.29) and patient age at the time of first recurrence (median (range) 55.5 (33.7-72.4) vs 55.0 (35.7-84.2) years; p=0.56). Initially, FIGO stage III disease was the most common in both two groups (55.8% vs 66.3%; p=0.20). Bevacizumab users were less likely to develop disease recurrence in the retroperitoneal lymph nodes (13.5% vs 34.6%; p=0.005), pelvis (17.3% vs 35.6%; p=0.018), and abdomen (40.4% vs 61.5%; p=0.012). However, no difference in distant metastasis was observed between the groups (23.1% vs 24.0%; p>0.99). Multivariate analyses adjusting for stage, histologic type, grade, platinum-free interval, and secondary debulking surgery revealed that the use of bevacizumab significantly reduced risks of nodal (adjusted HR (aHR) 0.24; 95% CI 0.10 to 0.56; p=0.001), pelvic (aHR 0.32; 95% CI 0.15 to 0.68; p=0.003), and abdominal recurrences (aHR 0.43; 95% CI 0.26 to 0.71; p=0.001). Nevertheless, use of bevacizumab did not influence risk of distant metastasis (aHR 0.70; 95% CI 0.35 to 1.40; p=0.32).

Conclusions: In patients with platinum-sensitive, recurrent epithelial ovarian cancer, second-line chemotherapy with bevacizumab is associated with reduced risks of nodal, pelvic, and abdominal recurrences, but similar risks of distant metastases.
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http://dx.doi.org/10.1136/ijgc-2020-001517DOI Listing
December 2020

Concordance between CA-125 and RECIST progression in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer treated in the SOLO2 trial with olaparib as maintenance therapy after response to chemotherapy.

Eur J Cancer 2020 11 23;139:59-67. Epub 2020 Sep 23.

Université Paris Descartes, Paris, France; ARCAGY-GINECO, France.

Background: Limited evidence exists to support CA-125 as a valid surrogate biomarker for progression in patients with ovarian cancer on maintenance PARP inhibitor (PARPi) therapy. We aimed to assess the concordance between CA-125 and Response Evaluation Criteria in Solid Tumours (RECIST) criteria for progression in patients with BRCA mutations on maintenance PARPi or placebo.

Methods: We extracted data on progression as defined by Gynecologic Cancer InterGroup CA-125, investigator- and independent central-assessed RECIST from the SOLO2/ENGOT-ov21(NCT01874353) trial. We excluded those with progression other than by RECIST, progression on date of randomisation, and no repeat CA-125 beyond baseline. We evaluated the concordance between CA-125 progression and RECIST progression, and assessed the negative (NPV) and positive predictive value (PPV).

Results: Of 295 randomised patients, 275 (184 olaparib, 91 placebo) were included. 171 patients had investigator-assessed RECIST progression. Of 80 patients with CA-125 progression, 77 had concordant RECIST progression (PPV 96%, 95% confidence interval 90-99%). Of 195 patients without CA-125 progression, 94 had RECIST progression (NPV 52%, 45-59%). Within treatment arms, PPV was similar (olaparib: 95% [84-99%], placebo: 97% [87-100%]) but NPV was lower in patients on placebo (olaparib: 60% [52-68%], placebo: 30% [20-44%]). Of 94 patients with RECIST but without CA-125 progression, 64 (68%) had CA-125 that remained within normal range. We observed similar findings using independent-assessed RECIST.

Conclusions: Almost half the patients without CA-125 progression had RECIST progression, and most of these had CA-125 within the normal range. Regular computed tomography imaging should be considered as part of surveillance in patients treated with or without maintenance olaparib rather than relying on CA-125 alone.
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http://dx.doi.org/10.1016/j.ejca.2020.08.021DOI Listing
November 2020

Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea.

Cancer Res Treat 2020 Oct 27;52(4):1229-1241. Epub 2020 Jul 27.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea.

Purpose: This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes.

Materials And Methods: We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment.

Results: The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135).

Conclusion: BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.
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http://dx.doi.org/10.4143/crt.2020.557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577800PMC
October 2020

A Randomized Controlled Trial of Thermo-Sensitive Sol-Gel Anti-Adhesion Agent after Gynecologic Surgery.

J Clin Med 2020 Jul 16;9(7). Epub 2020 Jul 16.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

Postoperative abdominal adhesions can lead to several adverse consequences such as pelvic pain, bowel obstruction, and infertility. We aimed to explore the anti-adhesion efficacy and safety of a thermo-sensitive sol-gel agent in patients who receive abdominopelvic surgery for benign gynecologic disease. This study was a randomized, controlled, single-blind clinical trial of women undergoing benign gynecologic surgery between January 2017 and December 2017. The patients were randomly assigned to three groups with a 1:1:1 ratio: experimental group (received the thermo-sensitive sol-gel agent), control group (untreated), and comparator group (received 4% icodextrin). Patients were followed for 4 weeks postoperatively, and efficacy was evaluated by performing the visceral slide test to identify adhesion formation. In total, 183 patients were enrolled in the study, and 178 (97.3%) completed the trial. The incidence rate of abdominal adhesion formation was significantly lower in the experimental group than in the control group (7.9% vs. 21.1%, = 0.040); however, it was similar between the experimental and comparator groups (7.9% vs. 13.8%. = 0.299). At 4 weeks, no differences in adhesion-related symptoms were observed between the experimental and control groups. Adverse events were mostly mild and did not differ significantly among the three groups ( = 0.375). In conclusion, use of a thermo-sensitive sol-gel agent was safe and effective to prevent abdominal adhesions after benign gynecologic surgeries.
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http://dx.doi.org/10.3390/jcm9072261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408806PMC
July 2020

Metagenomic Analysis of Serum Microbe-Derived Extracellular Vesicles and Diagnostic Models to Differentiate Ovarian Cancer and Benign Ovarian Tumor.

Cancers (Basel) 2020 May 21;12(5). Epub 2020 May 21.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

We aimed to develop a diagnostic model identifying ovarian cancer (OC) from benign ovarian tumors using metagenomic data from serum microbe-derived extracellular vesicles (EVs). We obtained serum samples from 166 patients with pathologically confirmed OC and 76 patients with benign ovarian tumors. For model construction and validation, samples were randomly divided into training and test sets in the ratio 2:1. Isolation of microbial EVs from serum samples of the patients and 16S rDNA amplicon sequencing were carried out. Metagenomic and clinicopathologic data-based OC diagnostic models were constructed in the training set and then validated in the test set. There were significant differences in the metagenomic profiles between the OC and benign ovarian tumor groups; specifically, genus was significantly more abundant in the OC group. More importantly, was the only common genus identified by seven different statistical analysis methods. Among the various metagenomic and clinicopathologic data-based OC diagnostic models, the model consisting of age, serum CA-125 levels, and relative abundance of showed the best diagnostic performance with the area under the receiver operating characteristic curve of 0.898 and 0.846 in the training and test sets, respectively. Thus, our findings establish a metagenomic analysis of serum microbe-derived EVs as a potential tool for the diagnosis of OC.
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http://dx.doi.org/10.3390/cancers12051309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281409PMC
May 2020

Clinical Desire for an Artificial Intelligence-Based Surgical Assistant System: Electronic Survey-Based Study.

JMIR Med Inform 2020 May 15;8(5):e17647. Epub 2020 May 15.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background: Techniques utilizing artificial intelligence (AI) are rapidly growing in medical research and development, especially in the operating room. However, the application of AI in the operating room has been limited to small tasks or software, such as clinical decision systems. It still largely depends on human resources and technology involving the surgeons' hands. Therefore, we conceptualized AI-based solo surgery (AISS) defined as laparoscopic surgery conducted by only one surgeon with support from an AI-based surgical assistant system, and we performed an electronic survey on the clinical desire for such a system.

Objective: This study aimed to evaluate the experiences of surgeons who have performed laparoscopic surgery, the limitations of conventional laparoscopic surgical systems, and the desire for an AI-based surgical assistant system for AISS.

Methods: We performed an online survey for gynecologists, urologists, and general surgeons from June to August 2017. The questionnaire consisted of six items about experience, two about limitations, and five about the clinical desire for an AI-based surgical assistant system for AISS.

Results: A total of 508 surgeons who have performed laparoscopic surgery responded to the survey. Most of the surgeons needed two or more assistants during laparoscopic surgery, and the rate was higher among gynecologists (251/278, 90.3%) than among general surgeons (123/173, 71.1%) and urologists (35/57, 61.4%). The majority of responders answered that the skillfulness of surgical assistants was "very important" or "important." The most uncomfortable aspect of laparoscopic surgery was unskilled movement of the camera (431/508, 84.8%) and instruments (303/508, 59.6%). About 40% (199/508, 39.1%) of responders answered that the AI-based surgical assistant system could substitute 41%-60% of the current workforce, and 83.3% (423/508) showed willingness to buy the system. Furthermore, the most reasonable price was US $30,000-50,000.

Conclusions: Surgeons who perform laparoscopic surgery may feel discomfort with the conventional laparoscopic surgical system in terms of assistant skillfulness, and they may think that the skillfulness of surgical assistants is essential. They desire to alleviate present inconveniences with the conventional laparoscopic surgical system and to perform a safe and comfortable operation by using an AI-based surgical assistant system for AISS.
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http://dx.doi.org/10.2196/17647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260656PMC
May 2020

Proteomic Discovery of Biomarkers to Predict Prognosis of High-Grade Serous Ovarian Carcinoma.

Cancers (Basel) 2020 Mar 26;12(4). Epub 2020 Mar 26.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

Initial identification of biomarkers predicting the exact prognosis of high-grade serous ovarian carcinoma (HGSOC) is important in precision cancer medicine. This study aimed to investigate prognostic biomarkers of HGSOC through proteomic analysis. We conducted label-free liquid chromatography-mass spectrometry using chemotherapy-naïve, fresh-frozen primary HGSOC specimens, and compared the results between a favorable prognosis group (progression-free survival (PFS) ≥ 18 months, = 6) and a poor prognosis group (PFS < 18 months, = 6). Among 658 differentially expressed proteins, 288 proteins were upregulated in the favorable prognosis group and 370 proteins were upregulated in the poor prognosis group. Using hierarchical clustering, we selected α1-antitrypsin (AAT), nuclear factor-κB (NFKB), phosphomevalonate kinase (PMVK), vascular adhesion protein 1 (VAP1), fatty acid-binding protein 4 (FABP4), platelet factor 4 (PF4), apolipoprotein A1 (APOA1), and α1-acid glycoprotein (AGP) for further validation via immunohistochemical (IHC) staining in an independent set of chemotherapy-naïve primary HGSOC samples ( = 107). Survival analyses revealed that high expression of AAT, NFKB, and PMVK were independent biomarkers for favorable PFS. Conversely, high expression of VAP1, FABP4, and PF4 were identified as independent biomarkers for poor PFS. Furthermore, we constructed models predicting the 18-month PFS by combining clinical variables and IHC results. Through leave-one-out cross-validation, the optimal model was based on initial serum CA-125, germline mutations, residual tumors after surgery, International Federation of Gynecology and Obstetrics (FIGO) stage, and expression levels of the six proteins. The present results elucidate the proteomic landscape of HGSOC and six protein biomarkers to predict the prognosis of HGSOC.
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http://dx.doi.org/10.3390/cancers12040790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226362PMC
March 2020

Impact of CT-Determined Sarcopenia and Body Composition on Survival Outcome in Patients with Advanced-Stage High-Grade Serous Ovarian Carcinoma.

Cancers (Basel) 2020 Feb 28;12(3). Epub 2020 Feb 28.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea.

This study aimed to investigate the impact of sarcopenia and body composition on survival outcomes in Korean patients with advanced-stage high-grade serous ovarian carcinoma (HGSOC). We retrospectively identified patients diagnosed with and treated for International Federation of Gynecology and Obstetrics stage III-IV HGSOC. Skeletal muscle index (SMI) was measured using pre-treatment computed tomography scans at the third lumbar vertebra. Sarcopenia was defined as SMI <39.0 cm/m. Patients' clinicopathologic characteristics and survival outcomes were compared according to sarcopenia presence. For subgroup analysis, we also measured the total fat area from the same image. In total, 76 and 103 patients were assigned to the sarcopenia and control groups, respectively. Comorbidities, stage, serum CA-125 levels, and size of residual tumor after surgery were similar between both groups. After a median follow up of 42.7 months, both groups showed similar progression-free survival (PFS) and overall survival (OS). In subgroup analysis confined to the sarcopenia group, patients with high fat-to-muscle ratio (FMR; ≥2.1, = 38) showed significantly worse OS than those with low FMR (<2.1, = 38) (5-year survival rate, 44.7% vs. 80.0%; = 0.046), whereas PFS was not different ( = 0.365). Multivariate analyses identified high FMR as an independent poor prognostic factor for OS in this group (adjusted hazard ratio, 3.377; 95% confidence interval, 1.1709.752; = 0.024). In conclusion, sarcopenia did not influence recurrence rates and survival in Korean patients with advanced-stage HGSOC. However, among the patients with sarcopenia, high FMR was associated with decreased OS.
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http://dx.doi.org/10.3390/cancers12030559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139516PMC
February 2020

Pathologic discrepancies between colposcopy-directed biopsy and loop electrosurgical excision procedure of the uterine cervix in women with cytologic high-grade squamous intraepithelial lesions.

J Gynecol Oncol 2020 Mar 22;31(2):e13. Epub 2019 Aug 22.

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Korea.

Objective: To investigate pathologic discrepancies between colposcopy-directed biopsy (CDB) of the cervix and loop electrosurgical excision procedure (LEEP) in women with cytologic high-grade squamous intraepithelial lesions (HSILs).

Methods: We retrospectively identified 297 patients who underwent both CDB and LEEP for HSILs in cervical cytology between 2015 and 2018, and compared their pathologic results. Considering the LEEP to be the gold standard, we evaluated the diagnostic performance of CDB for identifying cervical intraepithelial neoplasia (CIN) grades 2 and 3, adenocarcinoma in situ, and cancer (HSIL+). We also performed age subgroup analyses.

Results: Among the study population, 90.9% (270/297) had pathologic HSIL+ using the LEEP. The diagnostic performance of CDB for identifying HSIL+ was as follows: sensitivity, 87.8%; specificity, 59.3%; balanced accuracy, 73.6%; positive predictive value, 95.6%; and negative predictive value, 32.7%. Thirty-three false negative cases of CDB included CIN2,3 (n=29) and cervical cancer (n=4). The pathologic HSIL+ rate in patients with HSIL- by CDB was 67.3% (33/49). CDB exhibited a significant difference in the diagnosis of HSIL+ compared to LEEP in all patients (p<0.001). In age subgroup analyses, age groups <35 years and 35-50 years showed good agreement with the entire data set (p=0.496 and p=0.406, respectively), while age group ≥50 years did not (p=0.036).

Conclusion: A significant pathologic discrepancy was observed between CDB and LEEP results in women with cytologic HSILs. The diagnostic inaccuracy of CDB increased in those ≥50 years of age.
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http://dx.doi.org/10.3802/jgo.2020.31.e13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044015PMC
March 2020

Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells.

Nutrients 2019 Dec 19;12(1). Epub 2019 Dec 19.

Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.
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http://dx.doi.org/10.3390/nu12010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020042PMC
December 2019

Selection of patients with ovarian cancer who may show survival benefit from hyperthermic intraperitoneal chemotherapy: A systematic review and meta-analysis.

Medicine (Baltimore) 2019 Dec;98(50):e18355

Department of Obstetrics and Gynecology, Seoul National University College of Medicine.

Background: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis from various malignancies. However, the effectiveness of HIPEC for ovarian cancer is still controversial. Therefore, we performed this meta-analysis to identify patients with ovarian cancer who can obtain survival benefit from HIPEC.

Methods: Articles regarding HIPEC in the MEDLINE, EMBASE, and Cochrane Library were searched till December 2018. In total, 13 case-control studies and two randomized controlled trials were included in this meta-analysis. We investigated the effect of HIPEC on disease-free survival (DFS) and overall survival (OS), and performed subgroup analyses based on the study design, adjustment of confounding variables, and quality of the study.

Results: HIPEC improved both DFS (hazard ratio [HR], 0.603; 95% confidence interval [CI], 0.513-0.709) and OS (HR, 0.640; 95% CI, 0.519-0.789). In cases of primary disease, HIPEC improved DFS (HR, 0.580; 95% CI, 0.476-0.706) and OS (HR, 0.611; 95% CI, 0.376-0.992). Subgroup analyses revealed that HIPEC did not improve OS but improved DFS of patients with residual tumors ≤1 cm or no visible tumors. In cases of recurrent disease, HIPEC was associated with better OS (HR, 0.566; 95% CI, 0.379-0.844) but not with DFS. Subgroup analyses also revealed similar tendencies. However, HIPEC improved DFS of patients with residual tumors ≤1 cm or no visible tumors, while it improved OS of only those with residual tumors ≤1 cm.

Conclusions: HIPEC may improve DFS of patients with ovarian cancer when residual tumors were ≤1 cm or not visible. It may also improve OS of only patients with recurrent disease whose residual tumors were ≤1 cm.
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http://dx.doi.org/10.1097/MD.0000000000018355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922570PMC
December 2019

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

J Obstet Gynaecol Res 2020 Feb 9;46(2):337-346. Epub 2019 Dec 9.

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.

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.
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http://dx.doi.org/10.1111/jog.14171DOI Listing
February 2020

Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6.

Cancers (Basel) 2019 Dec 2;11(12). Epub 2019 Dec 2.

Department of Food and Nutrition, Kookmin University, Seoul 02707, Korea.

In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.
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http://dx.doi.org/10.3390/cancers11121917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966693PMC
December 2019

Real-World Experience of Olaparib Maintenance in High-Grade Serous Recurrent Ovarian Cancer Patients with Mutation: A Korean Multicenter Study.

J Clin Med 2019 Nov 8;8(11). Epub 2019 Nov 8.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Background: Olaparib maintenance therapy has shown efficacy and tolerability in patients with platinum-sensitive, high-grade serous recurrent ovarian cancer (HSROC) with BRCA1/2 mutation (BRCAm). Our aim was to present real-world experience with olaparib in Korea.

Method: We included HSROC patients with BRCAm treated with olaparib maintenance at four institutions in Korea between 2016 and 2018. Medical records were reviewed for clinico-pathologic characteristics, objective response, survival outcomes, and safety.

Results: One hundred HSROC patients with BRCAm were included. BRCA1 mutation was present in 71 patients (71.0%), and BRCA2 mutation was present in 23 patients (23.0%). In terms of the best objective response with olaparib maintenance in 53 patients with partial remission from most recent chemotherapy, complete remission occurred in 12 (22.6%) and partial remission in four (7.5%), while 33 patients (62.3%) had stable disease. The 24 month progression-free survival was 42.4%, and 24 month overall survival was 82.1%. Grade 3 or more adverse events were as follows: anemia in 14 patients (14.0%), neutropenia in seven patients (7.0%), thrombocytopenia in two patients (2.0%), oral mucositis in one patient (1.0%), and soft tissue infection in one patient (1.0%).

Conclusions: The safety and effectiveness of olaparib maintenance treatment in a real-world study were consistent with those reported in previous clinical trials.
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http://dx.doi.org/10.3390/jcm8111920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912318PMC
November 2019

Mitochondrial fission causes cisplatin resistance under hypoxic conditions via ROS in ovarian cancer cells.

Oncogene 2019 11 13;38(45):7089-7105. Epub 2019 Aug 13.

WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul, 08826, Republic of Korea.

Mitochondria undergo fission and fusion continually for survival through the course of cellular adaption processes in response to changes in the surrounding environment. Dysregulated mitochondrial dynamics has been reported in various diseases including cancer. Under hypoxic conditions (<1% O), the relationship between mitochondrial dynamics and sensitivity to cisplatin (CDDP) was examined in ovarian cancer cells. We found that hypoxia promoted mitochondrial fission and CDDP resistance in ovarian cancer cells. Hypoxia-induced reactive oxygen species (ROS) caused an increase in mitochondrial fission, a response abolished by free radical scavenging with N-acetylcysteine (NAC) and Trolox. Also, treatment of hydrogen peroxide (HO) decreased inhibitory p-Drp1 (Ser637) content and increased mitochondrial fission. Suppression of mitochondrial fission enhanced the CDDP sensitivity of hypoxic ovarian cancer cells. Lastly, in tumor spheroids from malignant ascites or tissues of patients with advanced-stage ovarian cancer, pretreatment with Mdivi-1 increased the CDDP sensitivity. Taken together, our results implicate that hypoxia-induced ROS trigger mitochondrial fission and CDDP resistance through downregulation of p-Drp1 (Ser637) and Mfn1 in ovarian cancer cells. Inhibition of Drp1 by Mdivi-1 treatment or si-Drp1 transfection increased CDDP sensitivity of ovarian cancer cells under hypoxia. Therefore, mitochondrial dynamics of cancer cells adapting to the hypoxic tumor microenvironment could be a potential target for anticancer therapy.
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http://dx.doi.org/10.1038/s41388-019-0949-5DOI Listing
November 2019

Impact of laparoscopic radical hysterectomy on survival outcome in patients with FIGO stage IB cervical cancer: A matching study of two institutional hospitals in Korea.

Gynecol Oncol 2019 10 2;155(1):75-82. Epub 2019 Aug 2.

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Objective: To compare survival outcomes of primary laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in patients with FIGO stage IB cervical cancer.

Methods: We retrospectively identified stage IB1-IB2 cervical cancer patients who received either LRH (n = 343) or ORH (n = 222) at two tertiary institutional hospitals between 2000 and 2018. To adjust for confounders, we conducted Mahalanobis distance-based sample matching for stage, histology, cervical mass size, parametrial invasion, and lymph node metastasis. Then, survival outcomes were compared between the matched groups. Through the independent matching processes, we narrowed the study population to stage IB1 patients and stage IB1 patients with tumor size ≤2 cm on pre-operative MRI.

Results: After matching, LRH group showed poorer progression-free survival (PFS) than ORH group (3-year: 85.4% vs. 91.8%; P = 0.036), whereas no significant difference in overall survival (OS) was found. Regarding recurrence patterns, no significant differences in the incidences of pelvic, retroperitoneal lymph node and abdominal recurrences, or distant metastasis were observed between the two groups. Among the matched patients with stage IB1 who had cervical mass size ≤2 cm, the LRH and ORH groups showed similar PFS (3-year: 90.0% vs. 93.1%; P = 0.8) and OS (5-year: 98.6% vs. 96.4%; P = 0.6).

Conclusions: Despite the retrospective design, our matched cohort study suggests that ORH might be preferable for the surgical treatment of FIGO stage IB cervical cancer. However, in stage IB1 patients with tumor size ≤2 cm, LRH might be applicable, as equivalent outcomes were found regardless of the surgical approach. Further prospective studies are warranted.
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http://dx.doi.org/10.1016/j.ygyno.2019.07.019DOI Listing
October 2019

Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer.

J Ovarian Res 2019 May 7;12(1):40. Epub 2019 May 7.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea.

Objective: To evaluate impact of germline BRCA mutational status on prognosis in patients with advanced ovarian cancer.

Methods: A total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study. We compared patients' clinicopathological characteristics and survival outcomes after primary treatment according to germline BRCA mutational status. Treatment-related factors that might affect patients' survival outcome were also investigated.

Results: Germline BRCA1/2 mutations were observed in 51 women (39.8%). There were no differences in age and serum CA-125 levels at the time of HGSOC diagnosis, use of neoadjuvant chemotherapy (NAC), extent of debulking surgery, and overall survival (OS) between the BRCA mutation and wild-type BRCA groups. In contrast, the BRCA mutation group displayed longer progression-free survival (PFS) (median, 22.9 vs. 16.9 months, P = 0.001). Multivariate analyses identified germline BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted HR, 0.502; 95% CI, 0.318-0.795; P = 0.003). In the wild-type BRCA group, patients who received NAC as the primary treatment had shorter PFS compared to those who received primary debulking surgery (PDS) (median, 14.2 vs. 16.9 months, P = 0.003). However, in the BRCA mutation group, PFS did not differ between the NAC and PDS groups (P = 0.082).

Conclusions: In advanced-stage HGSOC, patients with germline BRCA1/2 mutations have better prognosis with longer PFS than those lacking BRCA mutations. Prognosis after NAC was different according to the BRCA mutational status.
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http://dx.doi.org/10.1186/s13048-019-0511-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505247PMC
May 2019

Bevacizumab Efficacy and Recurrence Pattern of Persistent and Metastatic Cervical Cancer.

In Vivo 2019 May-Jun;33(3):863-868

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Background/aim: The aim of this study was to evaluate the efficacy of bevacizumab combined with cisplatin and paclitaxel for persistent, recurrent, or metastatic cervical cancer.

Materials And Methods: This is a retrospective review of medical records of patients with persistent, recurrent, or metastatic cervical cancer.

Results: Of the 52 patients, 33 (63.5%), 7 (13.5%) and 12 (23.1%) had recurrent, persistent and metastatic disease, respectively. Twenty-seven patients (51.9%) had prior platinum exposure. Possible bevacizumab-related serious adverse events included hypertension (n=3/52, 5.8%), febrile neutropenia (n=4/52, 7.7%) and fistula (n=2/52, 3.8%). Thirty-two recurrences (61.5%) and 20 deaths (38.5%) were noted. Median progression-free and overall survival was 9.8 months and 15.3 months, respectively. Recurrence included loco-regional (17/32, 59.4%), nodal (11/32, 34.4%), distant site (10/32, 31.3%) and peritoneal seeding (6/32, 18.8%).

Conclusion: Bevacizumab with cisplatin and paclitaxel for treating persistent, recurrent or metastatic cervical cancer is feasible and well tolerated. Loco-regional recurrence was most frequent. Overall survival was worse with recurrence at >2 sites or distant metastases.
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http://dx.doi.org/10.21873/invivo.11551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559922PMC
August 2019

Comparison of survival outcomes between minimally invasive surgery and conventional open surgery for radical hysterectomy as primary treatment in patients with stage IB1-IIA2 cervical cancer.

Gynecol Oncol 2019 04 12;153(1):3-12. Epub 2019 Jan 12.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: To compare survival outcomes of minimally invasive surgery (MIS) and conventional open surgery for radical hysterectomy (RH) among patients with early-stage cervical cancer (CC).

Methods: We retrospectively identified stage IB1-IIA2 CC patients who underwent either laparoscopic or open Type C RH between 2000 and 2018. Patients' clinicopathologic characteristics and survival outcomes were compared according to the surgical approach. For a more robust statistical analysis, we narrowed the study population down to the patients with stage IB1 who underwent pre-operative MRI.

Results: In total, 435 and 158 patients were assigned to open surgery and MIS groups, respectively. MIS group had significantly less parametrial invasion (6.3% vs. 15.4%; P = 0.004). Despite similar proportions of patients received adjuvant treatment, concurrent chemoradiation therapy was performed less frequently in MIS group. After a median follow up of 114.8 months, the groups showed similar overall survival; however, MIS group displayed poorer progression-free survival (PFS; 5-year rate, 78.5% vs. 89.7%; P < 0.001). Multivariate analyses identified MIS as an independent poor prognostic factor for PFS (adjusted HR, 2.883; 95% CI, 1.711-4.859; P < 0.001). Consistent results were observed among 349 patients with stage IB1: MIS was associated with higher recurrence rates (adjusted HR, 2.276; 95% CI, 1.039-4.986; P = 0.040). However, MIS did not influence PFS of stage IB1 patients with cervical mass size ≤2 cm on pre-operative MRI (adjusted HR, 1.146; 95% CI, 0.278-4.724; P = 0.850).

Conclusions: Overall, MIS RH was associated with higher recurrence rates than open RH in patients with early-stage CC. However, MIS was not a poor prognostic factor among those with stage IB1 and cervical mass size ≤2 cm on pre-operative MRI.
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http://dx.doi.org/10.1016/j.ygyno.2019.01.008DOI Listing
April 2019