Plasma-activated medium as a novel cancer therapeutic approach

Hiromasa TANAKA,Masaaki MIZUNO,Fumitaka KIKKAWA,Masaru HORI 한국진공학회 2016 한국진공학회 학술발표회초록집 Vol.2016 No.8

Prognostic value of neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma

Kosuke Yoshida,Nobuhisa Yoshikawa,Akira Shirakawa,Kaoru Niimi,Shiro Suzuki,Hiroaki Kajiyama,Fumitaka Kikkawa 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.6

Objectives: There is increasing evidence that systemic inflammatory response (SIR) markersare prognostic factors for various types of cancers. This is the first study to evaluate theusefulness of SIR markers for the prognosis of early-stage ovarian clear-cell carcinoma (OCCC). Methods: We retrospectively investigated 83 patients diagnosed with stage I–II OCCC whounderwent surgery between 2005 and 2017. Initially, receiver operating characteristic curveanalysis for overall survival (OS) was used to determine optimal cut-off values for neutrophilto-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Patients were stratifiedinto 2 groups by the cut-off values (NLR=3.26, PLR=160). Univariate and multivariateanalyses were performed to elucidate the significance of SIR markers as prognostic factors. Results: In the median follow-up period of 64.1 months, 16 patients experienced recurrence,and nine patients died. The Kaplan-Meier curve showed that OS of the NLR-low group wassignificantly longer than the NLR-high group (p=0.021). There was no significant differencein progression-free survival between the 2 groups (p=0.668), but the post-recurrencesurvival of the NLR-low group was significantly longer than the NLR-high group (p=0.019). Furthermore, multivariate analysis showed that increase in NLR is a significant independentprognostic factor for poor prognosis (hazard ratio=7.437, p=0.017). There was no significantdifference between PLR-low and PLR-high group. Conclusion: Results suggest that NLR can be a significant independent prognostic factor forearly-stage OCCC.

The impact of systematic retroperitoneal lymphadenectomy on long-term oncologic outcome of women with advanced ovarian clear-cell carcinoma

Hiroaki Kajiyama,Shiro Suzuki,Nobuhisa Yoshikawa,Satoshi Tamauchi,Kiyosumi Shibata,Fumitaka Kikkawa 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.4

Objective: The impact of systematic retroperitoneal lymphadenectomy (SRL) remainscontroversial in patients with advanced ovarian clear-cell carcinoma (CCC) who areoptimally debulked. Methods: Between 1986 and 2017, a total of 3,227 women with epithelial ovarian carcinomawere analyzed in a multi-institutional study. Among them, 166 optimally debulked womenwith stage IIB–IV CCC were collected (residual tumor of <1 cm). All patients were divided into2 groups: 1) Group I (n=112): underwent standard radical surgery with SRL, 2) Group II (n=54):underwent non-staging limited surgery. The pathological slides were assessed based on centralpathological review. Oncologic outcomes were compared between the two groups using apropensity score (PS)-matching technique to adjust for various clinicopathologic factors. Results: The median follow-up duration of all surviving women was 52.8 (1.6–184.2) months. Overall, 88 patients (53.0%) experienced recurrence and 68 patients (41.0%) died of thedisease. In the original cohort, the 5-year overall survival (OS) rates of groups I and II were57.9 and 64.9%, respectively (log-rank p=0.415). In the PS-adjusted cohort, the 5-year OSrates were 64.9 and 58.8% in women in groups I and II, respectively (p=0.453). Furthermore,in the PS-matched cohort after adjustment for multiple clinicopathologic factors, there wasno significant difference in OS between the 2 groups (group I vs. group II; hazard ratio=1.170;95% confidence interval=0.633–2.187; p=0.615). Conclusions: This study suggests that the performance of SRL including radical surgery maynot lead to a significant improvement in the oncologic outcome of advanced CCC patientswith optimal cytoreduction.

Prognostic factors and effects of fertility-sparing surgery in women of reproductive age with ovarian clear-cell carcinoma: a propensity score analysis

Masato Yoshihara,Hiroaki Kajiyama,Satoshi Tamauchi,Shiro Suzuki,Kunihiko Takahashi,Shigeyuki Matsui,Fumitaka Kikkawa 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.6

Objective: The aim of this study was to investigate the clinical characteristics of youngpatients with stage I clear-cell carcinoma (CCC) and evaluate the prognostic factors andeffects of fertility-sparing surgery (FSS) using propensity score (PS) adjustment. Methods: We conducted a regional multi-institutional study between 1986 and 2017. Among4,277 patients with ovarian tumor, clinical and pathological data of 103 fertile women withstage I unilateral CCC were collected. We evaluated survival and reproductive outcomesin these patients. Additionally, to analyze the effects of FSS, baseline imbalance betweenpatients with and those without FSS was adjusted with an inverse probability of treatmentweighting using PSs involving independent clinical variables. Results: The mean patient age was 39.4 years, and the median follow-up period for survivingpatients was 55.6 months. In multivariate analysis, stage IC2/IC3 (vs. IA/IC1) was the onlyindependent prognostic factor for recurrence-free survival (RFS) and overall survival (OS). FSS was not associated with poorer prognosis when compared to the prognosis with nonpreservingsurgery with regard to both RFS and OS. No statistical difference in survivaloutcomes between FSS and other approaches was confirmed after PS adjustment. Amongpatients who underwent FSS, four deliveries with healthy neonates were noted without anygestational complications. Conclusion: FSS can be considered in stage I CCC, specifically in stage IA and IC1 patientswho strongly desire to have children in the future. Further clinical research is needed toclarify the optimal application of FSS for CCC.

Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women

Nobuhisa Yoshikawa,Hiroaki Kajiyama,Mika Mizuno,Kiyosumi Shibata,Michiyasu Kawai,Tetsuro Nagasaka,Fumitaka Kikkawa 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.2

Objective: The purpose of this study was to clarify the clinical features of epithelial ovarian carcinoma (EOC) in younger vs. older patients in Japan. Methods: We collected data on 1,562 patients with EOC treated at multiple institutions in the Tokai Ovarian Tumor Study Group, and analyzed them retrospectively. All patients were divided into 2 groups: group A (≤40 years old) and group B (>40 years old). The data were analyzed to evaluate prognostic factors and the distribution of features in each group. Patients were subjected to univariate and multivariate analyses to evaluate overall survival (OS). Results: The median follow-up time was 45.1 months (range, 1 to 257 months). Patients in group A had a significantly higher rate of stage I disease (67.3% vs. 42.6%, respectively; p<0.001) and the mucinous type (36.7% vs. 13.5%, respectively; p<0.001) than those in group B. There was a significant difference of OS between the 2 groups (p=0.013). However, upon stratification according to the stage, there were no significant differences in the OS between the 2 groups (group A vs. B: stage I, p=0.533; stage II-IV, p=0.407). Multivariate analysis revealed that younger age was not an independent prognostic factor for OS. Conclusion: On the basis of our data, younger patients had a different clinical profile than older patients, particularly regarding the stage of the disease and pathological distribution; however, they showed a similar long-term prognosis, even upon stratification according to the stage.

Lipocalin-2: A novel biomarker for lung hypoplasia in congenital diaphragmatic hernia fetus

( Yoshinori Moriyama ),( Hiroyuki Tsuda ),( Tomomi Kotani ),( Seiji Sumigama ),( Tomoko Nakano ),( Shima Hirako ),( Fumitaka Kikkawa ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Objective: Congenital diaphragmatic hernia (CDH) results in pulmonary hypoplasia and pulmonary hypertension, which are often fatal. In order to improve clinical care and counseling, reliable prenatal parameters predicting outcome of CDH fetus are urgently needed. Some prenatal predictors of outcome of CDH fetus have been reported, but they are focused mainly on the assessment of fetal lung volume, and a gold-standard parameter has not yet been established. The aim of this study is to establish an accurate predictive marker for fetal lung hypoplasia in CDH cases. Methods: Neonatal lung tissue was collected at E21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9), and microarray analysis and real-time polymerase chain reaction (RT-PCR) were performed. Sixty-three human amniotic fluid samples of isolated CDH cases (n = 33) and scheduled Cesarean section (CS) without any fetal complication (controls) (n = 30) were obtained with signed informed consent. All amniotic fluid samples were obtained at CS performed at 35th to 38th weeks of gestation from April 2007 to January 2016. Results: Genes which showed significantly decreased expression in nitrofen-induced CDH lung were lipocalin-2 (9-fold) and GATA-2 (3.3-fold). In lipocalin-2, this result was confirmed by RT-PCR. Next, the lipocalin-2 level in human amniotic fluid was examined using ELISA, and it was significantly lower in CDH cases than in controls (73.7 ng/mL vs 163.8 ng/mL; p < 0.05). A significant positive correlation was observed between amniotic lipocalin- 2 level and lung area to head circumference ratio (p < 0.001, r² = 0.453). Conclusion: Our results suggest that gene expression level of lipocalin-2 was significantly decreased in hypoplastic lung in rats, and that amniotic lipocalin-2 level was significantly lower in CDH cases in human. Amniotic lipocalin- 2 can be a useful marker to predict the prognosis of fetal CDH.

Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology

Hiroaki Kajiyama,Kiyosumi Shibata,Mika Mizuno,Tomokazu Umezu,Shiro Suzuki,Ryuichiro Sekiya,Kaoru Niimi,Hiroko Mitsui,Eiko Yamamoto,Michiyasu Kawai,Tetsuro Nagasaka,Fumitaka Kikkawa 대한부인종양학회 2014 Journal of Gynecologic Oncology Vol.25 No.1

Objective: This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. Methods: Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. Results: The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes. Conclusion: Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.