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AIM The aim of this study was to evaluate the clinical performance for detecting cervical intraepithelial neoplasia (CIN) 2 or higher lesions among available human papillomavirus infection (HPV) genotyping tests in Korea. METHODS Eligible patients visited 13 tertiary hospitals for colposcopic biopsy following cervical cytology and HPV genotyping test between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected from 3798 patients. The performance of the Roche Cobas HPV 4800 was evaluated against other domestic HPV assays to detect CIN2 or higher. RESULTS A total of seven types of HPV genotyping tests were analyzed in the research institutes. A total of 1358 patients (35.8%) tested Anyplex II HPV 28 and 701 patients (18.5%) tested Cobas 4800 HPV. The overall sensitivity in the detection of CIN2 or higher was 41.5% (38.9-44.1) in patients positive for HPV 16/18. The Cobas test for HPV 16/18 was concordant with other assays evaluated for detection of CIN2 or higher and showed sensitivity of 46.6%, which was not significantly different from other assays. Although Anyplex II HPV28 (Seegene) showed slightly decreased sensitivity for detecting CIN2 or higher lesion with HPV 16/18 positive (39.8%, p

This study was performed to investigate the prevalence, clinical characteristics, and treatment response according to BRCA1 and BRCA2 (BRCA) mutations in Korean patients with epithelial ovarian cancer (EOC). Two‐hundred and ninety‐eight Korean women diagnosed with high‐grade serous and/or endometrioid EOC from 2010 to 2015 were tested for germline and 86 specimens for somatic BRCA mutations, regardless of the family history. Clinical characteristics including survival outcomes were compared in patients with and without BRCA mutations (NCT02963688). A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. Haplotype analysis demonstrated no founder mutations in our Korean patient cohort. Insignificant differences in age at diagnosis, primary site, and residual disease after surgery were observed between patients with and without BRCA mutations. In multivariate analysis for overall survival (OS), the presence of BRCA mutation was significantly associated with OS (P = .049) in addition to platinum sensitivity (P, A total of 43 different germline BRCA mutations were identified in 78 patients among 298 patients (26.2%). Somatic BRCA mutations were identified in 11 (12.8%) patients among patients without germline BRCA mutations. BRCA mutation is an independent prognostic factor for survival regardless of platinum sensitivity to first‐line chemotherapy. A higher response rate to subsequent chemotherapy after recurrence was observed in patients with BRCA mutation, resulting in better overall survival in these patients.

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.

Objective The aim of this study was to analyse patterns and timing of recurrence and their association with clinical outcomes in recurrent epithelial ovarian cancer (EOC) patients with no gross residual disease after primary debulking surgery (PDS). Methods This study was conducted on 303 EOC patients with no residual disease after PDS who were treated at the Samsung Medical Center from 2002 to 2012. By reviewing electronic medical records, information on date of clinical/pathological recurrence and pattern of disease presentation for each relapse were retrieved. Results Within a median follow-up of 53 months (range 3–156), 88 recurrences (29.0%) and 28 cancer-related deaths (9.2%) were observed. Most of the recurrences were distant, discrete and transcoelomic. After complete cytoreduction, the initial stage was associated with location of recurrence, but not with recurrence patterns. Complete cytoreduction reduced the number of recurrences, but it did not affect timing of recurrence. In multivariate analysis for overall survival (OS), patients with distant recurrence, diffuse carcinomatosis and mixed spread pattern of transcoelomic, lymphatic and haematogenous recurrence were found to have higher risk. Conclusions We found that timing of recurrence was not affected by complete cytoreduction. Location, type and pattern of recurrence were also significant prognostic factors for OS, in addition to known prognostic predictors such as platinum sensitivity.

Sphingosine kinase 1 (SK1) is over-expressed in multiple types of human cancer. SK1 has growth-promoting effects and has been proposed as a potential therapeutic target. We investigated the therapeutic effects of SK1 inhibition in epithelial ovarian carcinoma (EOC). SK1 siRNA or inhibitors were tested in EOC cell lines, including A2780, SKOV3ip1, A2780-CP20, SKOV3-TR, ES2 and RMG2. Cells were treated with SK inhibitor or FTY720, and cell proliferation, apoptosis, angiogenesis and invasion were examined by MTT, FACS, ELISA and wound-healing assays, respectively. In vivo experiments were performed to test the effects of FTY720 on tumor growth in orthotopic mouse xenografts of EOC cell lines A2780 or SKOV3ip1 and a patient-derived xenograft (PDX) model of clear cell ovarian carcinoma (CCC). Blocking SK1 with siRNA or inhibitors significantly reduced proliferation, angiogenesis and invasion, and increased apoptosis in chemosensitive (A2780 and SKOV3ip1) and chemoresistant (A2780-CP20, SKOV3-TR, ES2 and RMG2) EOC cells. SK1 inhibitors also decreased the intracellular enzymatic activity of SK1. Furthermore, FTY720 treatment significantly decreased the in vivo tumor weight in xenograft models of established cell lines (A2780 and SKOV3ip1) and a PDX model for CCC compared to control (p

Objective To identify risk factors for complications and conversion to laparotomy in women undergoing laparoscopically assisted vaginal hysterectomy (LAVH). Design Retrospective study. Setting Tertiary referral hospital. Population All 2012 consecutive women who underwent LAVH for non-malignant diseases in a single institution. Methods Retrospective study. Main outcome measures Operative complications and conversion to laparotomy. Results Most of the LAVHs were successful, but conversion to laparotomy was required in 97 women (4.8%) because of pelvic adhesion (n= 71), large uterine size (n= 18) or bowel injury (n= 8). There were 45 women (2.2%) with complications (bladder injury, 26; bowel injury, 9; vascular injury, 9; and ureteral injury, 1). A history of previous cesarean section (twice or more) was a significant risk factor for complications [odds ratio (OR) 3.38]. A body mass index ≥30 kg/m(2) (OR 2.98), history of previous myomectomy (OR 6.19) and uterine weight ≥500 g (OR 3.24) independently influenced the risk of conversion to laparotomy. Conclusions Risk factors identified in this study include a history of previous cesarean section (twice or more) and myomectomy, body mass index ≥30 kg/m(2) and uterine weight ≥500 g. The findings may be useful in counseling women preoperatively about the potential complications of LAVH.

A 52-year-old woman had undergone a partial cystectomy for a cystic mass at the dome of the urinary bladder in 1997. The pathological diagnosis was a urachal mucinous cystadenoma with borderline malignancy. Twelve years later, multiple masses were noted on the uterus, ovaries and abdominal wall. She underwent debulking surgery, including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, infracolic omentectomy, appendectomy, colon mass removal and abdominal wall mass removal. Remnants of the tumor were seeded throughout the abdominal cavity. The pathological evaluation confirmed metastatic urachal mucinous adenocarcinoma in both ovaries, the abdominal wall, the colon mass, the uterosacral ligament and the bladder. Adjuvant chemotherapy with paclitaxel and carboplatin was administered, which showed stable disease. She is now undergoing second-line chemotherapy.

Aims: To present our experience of modified laparoscopically assisted vaginal hysterectomy (LAVH) and to evaluate the surgical outcomes and complications. Methods: Women with benign gynaecologic tumours that underwent a modified LAVH at the Samsung Medical Centre were analysed retrospectively. The technique is primarily a vaginal hysterectomy with a minor component of the laparoscopic procedures (stage 2 laparoscopic hysterectomy (LH)) and had two modifications (vaginal anterior colpotomy and McCall culdoplasty) from the standard technique. Results: A total of 2012 LAVH procedures were performed from January 2000 to May 2008. The mean duration of the operations and the uterine weight were 102 ± 32 min and 305 ± 168 g, respectively. In 196 (9.7%) cases, the uterine weight was more than 500 g. Conversion to laparotomy was needed in 97 cases. Major intraoperative complications occurred in 45 cases (2.2%): bladder injury, 26 (1.29%); bowel injury, nine (0.45%); haemorrhage of major vessels, nine (0.45%); and ureteral injury, one (0.05%). Major long-term complications occurred in three cases: one fistula and two trocar site herniations. Conclusions: Stage 2 LH combined with modified vaginal anterior colpotomy and modified McCall culdoplasty is safe and effective for benign gynaecologic tumours and the prevention of post-LAVH vaginal prolapse.

BACKGROUND: Belotecan (CKD602; Camtobell, Chong Keun Dang Corp., Seoul, Korea) is a recently developed camptothecin derivative with antitumor properties. This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC). METHODS: Thirty-eight patients with recurrent EOC were treated with belotecan 0.3 mg/m2/day (days 1-5) and carboplatin AUC 5 (day 5) every 3 weeks for 6 cycles. The primary objective was to determine the response rate as defined by Response Evaluation Criteria in Solid Tumors and CA-125 response. Other end points included toxicities and progression-free survival (PFS). RESULTS: All 38 patients were assessed for toxicity, and 35 patients were assessed for response. The overall response rate was 57.1%; there were 7 complete responses (20.0%), 13 partial responses (37.1%), 6 patients with stable disease (17.1%), and 9 patients with progressive disease (25.7%). Grades 3 and 4 hematologic toxicities included neutropenia (28.8%), thrombocytopenia (19.8%), and anemia (14.4%), and there were 2 episodes of febrile neutropenia. Median PFS was 7 months, with a median follow-up of 12 months. CONCLUSIONS: The newly developed topoisomerase I inhibitor belotecan (CKD-602) combined with carboplatin is a well-tolerated regimen with activity in recurrent EOC. Further testing of this regimen is warranted to further characterize efficacy and indications for use. Cancer 2011. © 2010 American Cancer Society.

Aim: To better predict treatment responses for managing bulky cervical carcinoma with neoadjuvant chemotherapy (NAC). Methods: The expression of p-STAT3 was analyzed by immunohistochemistry using paraffin-embedded pretreatment cervical biopsy tissues. The study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with NAC. Results: Twenty (69.0%) of 29 patients were scored as p-STAT3-positive. Pathological response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%). The p-STAT3-positive patients had a longer disease-free survival compared to p-STAT3-negative patients (P = 0.03), though they had more frequent clinical nodal involvement (P = 0.046). Conclusion: Pretreatment assessment of p-STAT3 expression may provide additional information for the identification of patients with cervical cancer who have a favorable prognosis.

To evaluate the factors associated with physicians' choice of laparotomy or laparoscopy in pregnant women with presumptive benign ovarian tumors.Retrospective comparative analysis of pregnant women who underwent laparotomy or laparoscopy for ovarian tumors and who delivered at Samsung Medical Center, Seoul, Korea, between July 1995 and April 2008.Univariate analysis revealed that the following factors had a significant or a borderline significant association with the choice of operation type: maternal age (P=0.044); surgeon type (professor vs clinical fellow; P=0.094); tumor mass size (P=0.081); gestational age (P=0.035); and time since surgery (P0.001). Multivariate analysis showed that tumor size (P=0.030), gestational age (P=0.027), and time since surgery (P=0.004) were independent factors associated with physicians' choice of laparoscopy or laparotomy for the management of presumptive benign ovarian tumors during pregnancy.In the latter years of the present study, physicians at the study center preferred the laparoscopic approach for managing presumptive benign ovarian tumors during pregnancy. Furthermore, they preferred this approach to laparotomy for pregnancies at a relatively early gestational age and for treating small tumors.

Purpose: To investigate the feasibility of using multifunctional Fe3O4/TaOx(core / shell) nano particles developed for CT and MRI contrast agent as dose enhancing radiosensitizers. Methods: Firstly, to verify the imaging detectability of Fe3O4/TaOx nano particles, in-vivo tests were conducted. Approximately 600 mg/kg of 19 nm diameter Fe3O4/TaOx nano particles dispersed in phosphate buffered saline(PBS) were injected to ten nude Balb/c mice through the tail vein. Difference between pre- and post-injection images was analyzed by computing the pixel histogram and correlation coefficient factor using MATLAB in the user defined ROI. Secondly, to quantify the potential therapeutic enhancement with nano materials, DER (Dose Enhancement Ratio) and number of SER (Secondary Electron Ratio) were computed using TOPAS(ver.2.0 P-03) MC simulation. Results: In CT, MRI imaging, the aorta, the blood vessel, and the liver were clearly visualized after intravenous injection of Fe3O4/TaOx nano particles. There was large different between pre and post-injection images of Histogram data and Coefficients of correlation factor in CT and MR are 0.006, 0.060, respectively. When 70 MeV protons were irradiated for a Gold, Tantalum, TaOx, Fe3O4/TaOx, Fe3O4 nano particle, DER was 2.59, 2.41, 1.68, 1.54 and 1.36 respectively. Similarly, SER increment was 2.31, 2.15, 1.56, 1.46, and 1.27 for Gold, Tantalum, TaOx, Fe3O4/TaOx, Fe3O4 nano particle, respectively. Conclusion: Fe3O4/TaOx nano particles have potential as a multifunctional agent which enhances the accuracy in cancer detection through visualization of developed tumor lesion and increases the therapeutic effect in proton therapy. The dose enhancement with Fe3O4/TaOx was estimated as half of the Gold. However, tumor targeting such as combined with magnetic field may overcome the low DER. This research was supported by the NRF funded by the Ministry of Science, ICT & Future Planning (2012M3A9B6055201 and 2012R1A1A2042414), Samsung Medical Center grant[GFO1130081]