Jung Yun Lee

Trends in Gynecologic Cancer Mortality in East Asian Regions

Objective To evaluate uterine and ovarian cancer mortality trends in East Asian countries. Methods For three Asian countries and one region (Japan, Korea, Singapore, and Hong Kong), we extracted number of deaths for each year from the World Health Organization (WHO) mortality database, focusing on women ≥20 years old. The WHO population data were used to estimate person-years at risk for women. The annual age-standardized, truncated rates were evaluated for four age groups. We also compared age-specific mortality rates during three calendar periods (1979 to 1988, 1989 to 1998, and 1999 to 2010). Joinpoint regression was used to determine secular trends in mortality. To obtain cervical and uterine corpus cancer mortality rates in Korea, we re-allocated the cases with uterine cancer of unspecified subsite according to the proportion in the National Cancer Incidence Databases. Results Overall, uterine cancer mortality has decreased in each of the Asian regions. In Korea, corrected cervical cancer mortality has declined since 1993, at an annual percentage change (APC) of -4.8% (95% confidence interval [CI], -5.3 to -4.4). On the other hand, corrected uterine corpus cancer mortality has abruptly increased since 1995 (APC, 6.7; 95% CI, 5.4 to 8.0). Ovarian cancer mortality was stable, except in Korea, where mortality rates steadily increased at an APC of 6.2% (95% CI, 3.4 to 9.0) during 1995 to 2000, and subsequently stabilized. Conclusion Although uterine cancer mortality rates are declining in East Asia, additional effort is warranted to reduce the burden of gynecologic cancer in the future, through the implementation of early detection programs and the use of optimal therapeutic strategies.

Prognosis of Cervical Cancer in the Era of Concurrent Chemoradiation from National Database in Korea: A Comparison between Squamous Cell Carcinoma and Adenocarcinoma

In 1999, the National Cancer Institute issued a clinical advisory strongly touting the advantage of cisplatin-based chemoradiation (CCRT) for cervical cancer patients requiring radiation for their treatment. This study aimed to compare survival outcomes of cervical squamous cell carcinoma and adenocarcinoma before and after the advent of CCRT. Data were obtained from the Korea National Cancer Incidence Database for patients who were diagnosed with cervical cancers between 1993 and 2012. We compared survival according to histologic subtypes in cervical cancer patients diagnosed before (1993–1997), during (1998–2002), and after (2003–2012) the introduction of CCRT. A total of 80,766 patients were identified, including 64,531 (79.9%) women with squamous cell carcinomas and 7,265 (9.0%) with adenocarcinoma. With the introduction of CCRT, survival trends gradually increased in patients of both histologic subtypes with regional tumors. However, survival was significantly higher in squamous cell carcinoma than in adenocarcinoma patients regardless of treatment modalities (surgery alone, P < 0.001; surgery followed by CCRT, P < 0.001; or primary CCRT, P = 0.003). Multivariate analysis showed that adenocarcinoma was an independent negative prognostic factor for survival regardless of the time period (before CCRT, hazard ratio (HR) = 1.49; 95% confidence interval (CI), 1.37–1.62; after introduction of CCRT, HR = 1.40; 95% CI, 1.30–1.50). Although the survival of adenocarcinoma has improved after the introduction of CCRT, adenocarcinoma is still associated with worse overall survival compared to squamous cell carcinoma in the era of CCRT.

Luteolibacter yonseiensis sp. nov., isolated from activated sludge using algal metabolites.

A Gram-negative, rod-shaped, aerobic bacterial strain, designated EBTL01(T), was isolated from activated sludge by using metabolites of microalgae Ankistrodesmus gracilis SAG278-2. Phylogenetic analyses based on 16S rRNA gene sequence showed that strain EBTL01(T) belongs to the family Verrucomicrobiaceae, class Verrucomicrobiae, and is related most closely to Luteolibacter pohnpeiensis A4T-83(T) (95.5 % sequence similarity) and Luteolibacter algae A5J-41-2(T) (95.2 %). The G+C content of the genomic DNA of strain EBTL01(T) was 56.3 mol% and the menaquinone MK-9 was detected as the predominant quinone. Major fatty acid components were iso-C14 : 0, C16 : 1ω7c and C16 : 0. The amino acids of the cell-wall peptidoglycan contained muramic acid and meso-diaminopimelic acid. These profile results supported the affiliation of strain EBTL01(T) to the genus Luteolibacter. On the other hand, based on chemotaxonomic properties and phenotypic characteristics, strain EBTL01(T) could be clearly differentiated from its phylogenetic neighbours. Therefore, strain EBTL01(T) represents a novel species of the genus Luteolibacter, for which the name Luteolibacter yonseiensis sp. nov. is proposed. The type strain is EBTL01(T) ( = KCTC 23678(T) = JCM 18052(T)).

Cost-effectiveness of para-aortic lymphadenectomy before chemoradiotherapy in locally advanced cervical cancer

Objective To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). Methods A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. Results We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was

Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice

19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of

Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients

60,000/QALY. Conclusion Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines.

Preoperative assessment of lymph node metastasis in endometrial cancer: A Korean Gynecologic Oncology Group study

Background/Objectives:We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice.Methods:Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg−1 daily) was injected intraperitoneally for 20 weeks.Results:Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes.Conclusions:Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Role of systematic lymphadenectomy as part of primary debulking surgery for optimally cytoreduced advanced ovarian cancer: Reappraisal in the era of radical surgery

Purpose The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type). Materials and Methods We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status. Results Thirty-seven (37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively). Conclusion Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

Primary and recurrent ovarian high-grade serous carcinomas display similar microRNA expression patterns relative to those of normal ovarian tissue

Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed.

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer

The prognostic significance of pelvic and para-aortic lymphadenectomy during primary debulking surgery for advanced-stage ovarian cancer remains unclear. This study aimed to evaluate the survival impact of lymph node dissection (LND) in patients treated with optimal cytoreduction for advanced ovarian cancer. Data from 158 consecutive patients with stage IIIC–IV disease who underwent optimal cytoreduction (<1 cm) were obtained via retrospective chart review. Patients were classified into two groups: (1) lymph node sampling (LNS), node count <20; and (2) LND, node count ≥20. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Among the included patients, 96 and 62 patients underwent LND and LNS as primary debulking surgery, respectively. There were no differences in the extent of debulking surgical procedures, including extensive upper abdominal surgery, between the groups. Patients who underwent LND had a marginally significantly improved PFS (P = 0.059) and significantly improved OS (P < 0.001) compared with those who underwent LNS. In a subgroup with negative lymphadenopathy on preoperative computed tomography scans, revealed LND correlated with a better PFS and OS (P = 0.042, 0.001, respectively). Follow-ups of subsequent recurrences observed a significantly lower nodal recurrence rate among patients who underwent LND. A multivariate analysis identified LND as an independent prognostic factor for PFS (hazard ratio [HR], 0.629; 95% confidence interval [CI], 0.400–0.989) and OS (HR, 0.250; 95% CI, 0.137–0.456). In conclusion, systematic LND might have therapeutic value and improve prognosis for patients with optimally cytoreduced advanced ovarian cancer.