Disparities between Uptake of Germline BRCA1/2 Gene Tests and Implementation of Post-test Management Strategies in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

Background@#To assess the rate of germline BRCA gene tests in epithelial ovarian cancer (EOC) patients and uptake of post-test risk management strategies in BRCA1/2-mutated patients. @*Methods@#Institutional databases were searched to identify patients who were diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) between 2009 and 2019 in two academic hospitals. Retrospective review on medical records was performed to collect clinico-pathologic variables, including performance of germline BRCA gene test and its results, as well as conduct of breast cancer screening tests and cascade testing. If annual mammography +/− breast ultrasonography was performed, it was considered that regular breast cancer surveillance was done. @*Results@#A total of 840 women with EOC were identified during the study period. Of these, 454 patients (54.0%) received BRCA gene testing and 106 patients (106/454, 23.3%) were positive for BRCA1/2 mutations. The rate of BRCA tests has markedly increased from 25.8% in 2009-2012 to 62.7% in 2017-2019. Among the 93 patients with BRCA1/2 mutation without previous personal breast cancer history, 20 patients (21.5%) received annual mammography with or without breast ultrasonography for regular surveillance. Among the 106 BRCA1/2-mutated EOC patients, cascade testing on family members was performed only in 13 patients (12.3%). @*Conclusion@#Although BRCA1/2 gene tests have been substantially expanded, the uptake of post-test risk management strategies, including breast cancer screening for BRCA1/2-mutated patients and cascade testing for family members, has remained low. Strategies to increase its uptake and education about the importance of post-test risk managements are needed.

Primary Lymphoma of Cervix / 이화의대지

Lymphomas that originate from the female genital tract are very rare. Primary cervical lymphoma only accounts for less than 1% of all extra-nodal lymphomas. Clinical manifestations of primary cervical lymphoma can be nonspecific, vaginal bleeding being the most common symptom, and this makes timely diagnosis often difficult. Prognosis and optimal treatment have yet been established due to the rarity of the disease. In this article, a rare case of primary diffuse large B-cell lymphoma of cervix is reported with a review of the available literature.

Disparities between Uptake of Germline BRCA1/2 Gene Tests and Implementation of Post-test Management Strategies in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

Background@#To assess the rate of germline BRCA gene tests in epithelial ovarian cancer (EOC) patients and uptake of post-test risk management strategies in BRCA1/2-mutated patients. @*Methods@#Institutional databases were searched to identify patients who were diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal cancer (EOC) between 2009 and 2019 in two academic hospitals. Retrospective review on medical records was performed to collect clinico-pathologic variables, including performance of germline BRCA gene test and its results, as well as conduct of breast cancer screening tests and cascade testing. If annual mammography +/− breast ultrasonography was performed, it was considered that regular breast cancer surveillance was done. @*Results@#A total of 840 women with EOC were identified during the study period. Of these, 454 patients (54.0%) received BRCA gene testing and 106 patients (106/454, 23.3%) were positive for BRCA1/2 mutations. The rate of BRCA tests has markedly increased from 25.8% in 2009-2012 to 62.7% in 2017-2019. Among the 93 patients with BRCA1/2 mutation without previous personal breast cancer history, 20 patients (21.5%) received annual mammography with or without breast ultrasonography for regular surveillance. Among the 106 BRCA1/2-mutated EOC patients, cascade testing on family members was performed only in 13 patients (12.3%). @*Conclusion@#Although BRCA1/2 gene tests have been substantially expanded, the uptake of post-test risk management strategies, including breast cancer screening for BRCA1/2-mutated patients and cascade testing for family members, has remained low. Strategies to increase its uptake and education about the importance of post-test risk managements are needed.

Effect of Quality Control Program in Surgical Management of Early Cervical Cancer

Background@#Regular assessments of clinical performance in gynecologic cancer surgery is important for the safety of patients. We evaluated the effects of quality control (QC) program on the treatment pattern and clinical outcomes of early cervical cancer. @*Methods@#Medical records of cervical cancer patients who received operation in our institution from January 2007 to December 2018 were retrospectively reviewed. Cases were divided into 2 groups, before and after the initiation of QC program, group 1 (2007–2013) and group 2 (2014–2018), based on the operation date. Two groups were compared in clinicopathologic variables, surgical methods, operative details, adjuvant treatments, recurrence and survival. @*Results@#A total of 305 cervical cancer patients were included in the analysis, 210 in group 1 and 95 in group 2. In group 2, minimally invasive surgery (MIS) was more frequently performed (60.0% vs. 76.8%, P = 0.004), especially in earlier stages (stage IA, 72.6% vs. 100.0%; stage IB, 52.2% vs. 69.5%). However, the median tumor size treated by MIS was decreased in stage IB (20 mm vs. 17 mm, P = 0.015). Frequency of adjuvant treatment was also reduced in stage IB (56.5% vs. 37.3%, P = 0.016). Recurrence within 3 years, 3-year disease free survival and overall survival did not show significant difference; however, 3-year recurrence after MIS was significantly reduced in stage IB. @*Conclusion@#QC program enforced stricter patient selection criteria for MIS and positively affected clinical outcomes in cervical cancer patients who underwent surgery. Systemic monitoring should be considered for patient safety.

Primary Lymphoma of Cervix / 이화의대지

Lymphomas that originate from the female genital tract are very rare. Primary cervical lymphoma only accounts for less than 1% of all extra-nodal lymphomas. Clinical manifestations of primary cervical lymphoma can be nonspecific, vaginal bleeding being the most common symptom, and this makes timely diagnosis often difficult. Prognosis and optimal treatment have yet been established due to the rarity of the disease. In this article, a rare case of primary diffuse large B-cell lymphoma of cervix is reported with a review of the available literature.

Medical Issues and Opinions of Obstetrics Regarding Abortion Law Amendment

There have been ongoing social discussions on revision of the abortion law since the Constitutional Court ruled it nonconformity to the constitution on April 11, 2019. Thus, Korean Society of Obstetrics and Gynecology, Korean Society of Maternal Fetal Medicine, Korean College of Obstetricians and Gynecologists, and Korean Association of Obstetricians and Gynecologists organized 'special committee for abortion law' to support social discussion on the revision of the abortion law, and they prepared official opinions of obstetrics for medical issues including doctors' right to refuse abortion. In the future, the committee will continue to adapt to changes of medical environment especially after the revision of the abortion law by collecting its members' feedbacks.

Medical Issues and Opinions of Obstetrics Regarding Abortion Law Amendment

There have been ongoing social discussions on revision of the abortion law since the Constitutional Court ruled it nonconformity to the constitution on April 11, 2019. Thus, Korean Society of Obstetrics and Gynecology, Korean Society of Maternal Fetal Medicine, Korean College of Obstetricians and Gynecologists, and Korean Association of Obstetricians and Gynecologists organized 'special committee for abortion law' to support social discussion on the revision of the abortion law, and they prepared official opinions of obstetrics for medical issues including doctors' right to refuse abortion. In the future, the committee will continue to adapt to changes of medical environment especially after the revision of the abortion law by collecting its members' feedbacks.

Minimally invasive surgery for radical hysterectomy in women with cervical cancer: Korean Society of Gynecologic Oncology, Korean Society of Obstetrics and Gynecology, and Korean Society of Gynecologic Endoscopy and Minimally Invasive Surgery position statement / 부인종양

On the basis of emerging data and the current understanding of minimally invasive surgery (MIS) for radical hysterectomy (RH) in women with cervical cancer, the Korean Society of Gynecologic Oncology, Korean Society of Obstetrics and Gynecology, and Korean Society of Gynecologic Endoscopy and Minimally Invasive Surgery support the following recommendations: • According to the recently published phase III Laparoscopic Approach to Cervical Cancer (LACC) trial—a prospective randomized clinical trial—disease-free survival and overall survival rates of MIS RH are significantly lower than those of open RH. • Gynecologic oncologists should be aware of the emerging data on MIS RH for early-stage cervical cancer. • The results of the LACC trial, together with institutional data, should be discussed with patients before choosing MIS RH. • MIS RH should be performed for optimal candidates according to the current practice guidelines by gynecologic oncologists who are skilled at performing MIS.

The 34th Annual Meeting of the Korean Society of Gynecologic Oncology 2019: meeting report / 부인종양

The 34th Annual Meeting of Korean Society of Gynecologic Oncology (KSGO) was held in Busan, Korea from 26 to 27 April. Around 460 Korean and international clinicians gathered in Busan to share and discuss their latest work and key issues of gynecologic oncologic research and treatment. The scope of this meeting included recent clinical trials and updates in gynecologic oncology, advances in ovarian cancer treatment, targeted therapy and immunotherapy in gynecologic cancer, management of hereditary gynecologic cancer, and newly revised staging of cervical cancer. As expected, the ongoing debate regarding the recent clinical trial on minimally invasive surgery for early-stage cervical cancer was addressed throughout the congress and the initial outline of the KSGO position statement was open for discussion. The meeting was an opportunity for all participants to come together and explore scientific insights of gynecologic cancer.

Asian Society of Gynecologic Oncology International Workshop 2018 / 부인종양

The Asian Society of Gynecologic Oncology International Workshop 2018 on gynecologic oncology was held in the Ajou University Hospital, Suwon, Korea on the 24th to 25th August 2018. The workshop was an opportunity for Asian doctors to discuss the latest findings of gynecologic cancer, including cervical, ovarian, and endometrial cancers, as well as the future of fertility-sparing treatments, minimally invasive/radical/debulking surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Clinical guidelines and position statement of Asian countries were presented by experts. Asian clinical trials for gynecologic cancers were reviewed and experts emphasized the point that original Asian study is beneficial for Asian patients. In Junior session, young gynecologic oncologists presented their latest research on gynecologic cancers.

The 2018 Beijing-Seoul-Tokyo Obstetrics and Gynecology Summit Forum

No abstract available.

Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers. MATERIALS AND METHODS: A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening. RESULTS: Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine. CONCLUSION: MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.

14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.

Prevention of lymphocele by using gelatin-thrombin matrix as a tissue sealant after pelvic lymphadenectomy in patients with gynecologic cancers: a prospective randomized controlled study / 부인종양

OBJECTIVE: This prospective randomized controlled pilot study aimed to find whether gelatin-thrombin matrix used as a tissue sealant (FloSeal) can prevent the occurrence of pelvic lymphocele in patients with gynecologic cancer who has undergone pelvic lymphadenectomy. METHODS: Each patient, who undergo a laparotomic pelvic lymph node dissection on both sides, was randomly assigned for FloSeal application on 1 side of the pelvis. The other side of the pelvis without any product application being the control side. The amount of lymph drainage at each side of the pelvis was measured for 3 days, and computed tomography scans were obtained 7 days and 6 months after surgery for detection of pelvic lymphocele. RESULTS: Among 37 cases, the median amount of lymph drainage was significantly decreased in the hemi-pelvis treated with FloSeal compared to the control hemi-pelvis (p=0.025). The occurrence of lymphocele was considerably reduced in treated hemi-pelvis (8/37, 21.6%) compared with control hemi-pelvis (12/37, 32.4%) after 7 post-operative days (p=0.219), and more decreased in the treated hemi-pelvis (5/37, 13.5%) compared with control hemi-pelvis (9/37, 24.3%) after postoperative 6 months (p=0.344). CONCLUSION: The application of FloSeal as a tissue sealant in lymph nodes resected tissues can reduce the incidence of pelvic lymphocele in gynecologic cancer patients. A large randomized controlled study could confirm these preliminary results.

Development and validation of novel digitalized cervicography system

OBJECTIVE: Digital cervicography systems would be expected to reduce the costs of film cervicography, and provide the opportunity for "telemedicine-based" screening. We aimed to develop web-based digital cervicography system, and validate it compared with conventional film cervicography. METHODS: A hundred cases from five centers were prospectively included, and cervical images (analogue, digitalized by scanning analogue, and digital) were taken separately using both analogue (Cerviscope) and digital camera (Dr. Cervicam) in each patient. Nine specialists evaluated the three kinds of images of each case with time interval between evaluations of each image. To validate novel digitalized system, we analyzed intra-observer variance among evaluation results of three kinds of images. RESULTS: Sixty-three cases were finally analyzed after excluding technically defective cases that cannot be evaluable on analogue images. The generalized kappa for analogue versus digital image was 0.83, for analogue versus scanned image 0.72, and for digital versus scanned image was 0.71; all were in excellent consensus. CONCLUSION: Digitalized cervicography system can be substituted for the film cervicography very reliably, and can be used as a promising telemedicine tool for cervical cancer screening.

Recent advances in ovarian cancer treatment

No abstract available.

Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

Treatment outcomes after adjuvant radiotherapy following surgery for patients with stage I endometrial cancer

PURPOSE: The purpose of this study is to evaluate the treatment outcomes of adjuvant radiotherapy using vaginal brachytherapy (VB) with a lower dose per fraction and/or external beam radiotherapy (EBRT) following surgery for patients with stage I endometrial carcinoma. MATERIALS AND METHODS: The subjects were 43 patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer who underwent adjuvant radiotherapy following surgery between March 2000 and April 2014. Of these, 25 received postoperative VB alone, while 18 received postoperative EBRT to the whole pelvis; 3 of these were treated with EBRT plus VB. The median EBRT dose was 50.0 Gy (45.0–50.4 Gy) and the VB dose was 24 Gy in 6 fractions. Tumor dose was prescribed at a depth of 5 mm from the cylinder surface and delivered twice per week. RESULTS: The median follow-up period for all patients was 57 months (range, 9 to 188 months). Five-year disease-free survival (DFS) and overall survival (OS) for all patients were 92.5% and 95.3%, respectively. Adjuvant radiotherapy was performed according to risk factors and stage IB, grade 3 and lymphovascular invasion were observed more frequently in the EBRT group. Five-year DFS for EBRT and VB alone were 88.1% and 96.0%, respectively (p = 0.42), and 5-year OS for EBRT and VB alone were 94.4% and 96%, respectively (p = 0.38). There was no locoregional recurrence in any patient. Two patients who received EBRT and 1 patient who received VB alone developed distant metastatic disease. Two patients who received EBRT had severe complications, one each of grade 3 gastrointestinal complication and pelvic bone insufficiency fracture. CONCLUSION: Adjuvant radiotherapy achieved high DFS and OS with acceptable toxicity in stage I endometrial cancer. VB (with a lower dose per fraction) may be a viable option for selected patients with early-stage endometrial cancer following surgery.

Association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer

OBJECTIVE: Decreased adiponectin and increased leptin plasma concentrations are believed to be associated with the occurrence and progression of cancers such as endometrial cancer and breast cancer. The aim of this study was to explore the association of plasma adiponectin and leptin levels with the development and progression of ovarian cancer. METHODS: For patients with ovarian cancer and the control group, adiponectin and leptin levels were measured; anthropometric data were obtained during a chart review. Statistical comparisons between groups were analyzed using the Student's t-test; correlations were confirmed using the Pearson correlation. RESULTS: The mean adiponectin and leptin concentrations in patients with ovarian cancer were lower than those of the control group (8.25 vs. 11.44 µg/mL, respectively; P=0.026) (7.09 vs. 15.4 ng/mL, respectively; P=0.001). However, there was no significant difference in adiponectin and leptin levels between early-stage (I/II) and advanced-stage (III/IV) disease (P=0.078). CONCLUSION: Compared with other gynecological cancers, the level of adiponectin and leptin were decreased in ovarian cancer that may have some diagnostic value; additional study to elucidate the function of these two hormones in the development of ovarian carcinogenesis is necessitated.

Prognostic analysis of uterine cervical cancer treated with postoperative radiotherapy: importance of positive or close parametrial resection margin

PURPOSE: To analyze prognostic factors for locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) in cervical cancer patients who underwent radical hysterectomy followed by postoperative radiotherapy (PORT) in a single institute. MATERIALS AND METHODS: Clinicopathologic data of 135 patients with clinical stage IA2 to IIA2 cervical cancer treated with PORT from 2001 to 2012 were reviewed, retrospectively. Postoperative parametrial resection margin (PRM) and vaginal resection margin (VRM) were investigated separately. The median treatment dosage of external beam radiotherapy (EBRT) to the whole pelvis was 50.4 Gy in 1.8 Gy/fraction. High-dose-rate vaginal brachytherapy after EBRT was given to patients with positive or close VRMs. Concurrent platinum-based chemoradiotherapy (CCRT) was administered to 73 patients with positive resection margin, lymph node (LN) metastasis, or direct extension of parametrium. Kaplan-Meier method and log-rank test were used for analyzing LRR, DM, and OS; Cox regression was applied to analyze prognostic factors. RESULTS: The 5-year disease-free survival was 79% and 5-year OS was 91%. In univariate analysis, positive or close PRM, LN metastasis, direct extension of parametrium, lymphovascular invasion, histology of adenocarcinoma, and chemotherapy were related with more DM and poor OS. In multivariate analysis, PRM and LN metastasis remained independent prognostic factors for OS. CONCLUSION: PORT after radical hysterectomy in uterine cervical cancer showed excellent OS in this study. Positive or close PRM after radical hysterectomy in uterine cervical cancer correlates with poor prognosis even with CCRT. Therefore, additional treatments to improve local control such as radiation boosting need to be considered.