Quality indicators for cervical cancer care in Japan

Tomone Watanabe,Mikio Mikami,Hidetaka Katabuchi,Shingo Kato,Masanori Kaneuchi,Masahiro Takahashi,Hidekatsu Nakai,Satoru Nagase,Hitoshi Niikura,Masaki Mandai,Yasuyuki Hirashima,Hiroyuki Yanai,Wataru Ya 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.6

Objective: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. Methods: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. Results: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI], 1.2–70.9) and grade 3 histology (HR=7.28; 95% CI, 1.45–36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI, 1.38–19.1) and DSS (HR=5.97; 95% CI, 1.06–58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. Conclusion: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC. Objective: We aimed to propose a set of quality indicators (QIs) based on the clinical guidelines for cervical cancer treatment published by The Japan Society of Gynecologic Oncology, and to assess adherence to standard-of-care as an index of the quality of care for cervical cancer in Japan. Methods: A panel of clinical experts devised the QIs using a modified Delphi method. Adherence to each QI was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2013, and linked with insurance claims data, between October 1, 2012, and December 31, 2014. All patients who received first-line treatment at the participating facility were included. The QI scores were communicated to participating hospitals, and additional data about the reasons for non-adherence were collected. Results: In total, 297 hospitals participated, and the care provided to 15,163 cervical cancer patients was examined using 10 measurable QIs. The adherence rate ranged from 50.0% for ‘cystoscope or proctoscope for stage IVA’ to 98.8% for ‘chemotherapy using platinum for stage IVB’. Despite the variation in care, hospitals reported clinically valid reasons for more than half of the non-adherent cases. Clinically valid reasons accounted for 75%, 90.9%, 73.4%, 44.5%, and 88.1% of presented non-adherent cases respectively. Conclusion: Our study revealed variations in pattern of care as well as an adherence to standards-of-care across Japan. Further assessment of the causes of variation and non-adherence can help identify areas where improvements are needed in patient care.

The use of conization to identify and treat severe lesions among prediagnosed CIN1 and 2 patients in Japan

Mikio Mikami,Masae Ikeda,Hidetaka Sato,Haruko Iwase,Takayuki Enomoto,Yoichi Kobayashi,Hidetaka Katabuchi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.4

OBJECTIVE: To evaluate the clinical efficiency of identifying patients with suspicious severe lesions by conization among prediagnosed cervical intraepithelial neoplasia (CIN) 1 and 2 patients in Japan. METHODS: The data in a Japanese nation-wide registry for cervical cancer (2009 and 2011) was collected to analyze the clinical efficacy of pre- and postdiagnosis for 13,215 Japanese women who underwent treatment by conization. Their preoperative and postoperative histologic findings and clinical outcomes were evaluated using standard statistical procedures including clinical and demographic characteristics. RESULTS: Almost half of 1,536 women who were treated by conization after the prediagnosis of CIN1 and 2 because the lesions showed no evidence of natural regression actually contained CIN1-2 (45.0%), CIN3 (47%), or invasive cancer (2.7%) in their cervical tissue. They underwent conization either for therapeutic (treatment) (78.5%) or diagnostic (21.5%) reasons. Invasive disease was diagnosed postoperatively more often in diagnostic cases (6.1%) than in therapeutic cases (2.8%). All the patients survived their diagnostic and therapeutic conization after approximately 30 months of follow up. CONCLUSION: Our study shows that the continuous observation of the prediagnosed CIN1 and 2 cases by the combination of cytology, colposcopy and histology in Japan has worked successfully to identify severe lesions by using conization as well in the process.

Impact of institutional accreditation by the Japan Society of Gynecologic Oncology on the treatment and survival of women with cervical cancer

Mikio Mikami,Masako Shida,Takeo Shibata,Hidetaka Katabuchi,Junzo Kigawa,Daisuke Aoki,Nobuo Yaegashi 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.2

Objective: The Japan Society of Gynecologic Oncology (JSGO) initiated a nation-wide training system for the education and certification for gynecologic oncologists in 2005. To assess the impact of the quality of the JSGO-accredited institutions, JSGO undertook an analysis of the Uterine Cervical Cancer Registry of the Japan Society of Obstetrics and Gynecology (JSOG) to determine the effectiveness of the JSGO-accredited institutions on the treatment and survival of women with cervical cancer. Methods: The effectiveness of 119 JSGO-accredited institutions and 125 non-JSGO-accredited institutions on the treatment and survival of women with cervical cancer were compared by analyzing the tumor characteristics, treatment patterns, and survival outcomes of women with stage T1B–T4 cervical cancer utilizing the data in the JSOG nation-wide registry for cervical cancer (2006–2009). Results: A total of 14,185 eligible women were identified: 10,920 (77.0%) cases for 119 JSGO-accredited institutions and 3,265 (23.0%) cases for 125 non-accredited institutions. A multivariate analysis showed that age, stage, histology type, and treatment pattern were independently associated with mortality. Moreover, women who received treatment at the JSGO-accredited institutions had a significantly decreased mortality risk compared to non-accredited institutions (adjusted hazard ratio [aHR]=0.843; 95% confidence interval [CI]=0.784–0.905). Similar findings on multivariate analysis were seen among subset of women who received surgery alone (aHR=0.552; 95% CI=0.393–0.775) and among women who received radiotherapy (aHR=0.845; 95% CI=0.766–0.931). Conclusion: Successful implementation of gynecologic oncology accrediting institution was associated with improved survival outcome of women with cervical cancer in Japan.

STAT3 pathway of epithelial ovarian cancer cells and M2 macrophages in the cancer microenvironment are inactivated by Onionin A

( Junko Tsuboki ),( Kiyomi Takaishi ),( Fumiko Ito ),( Ritsuo Honda ),( Hironori Tashiro ),( Hidetaka Katabuchi ) 대한산부인과학회 2016 대한산부인과학회 학술대회 Vol.102 No.-

Objective: In epithelial ovarian cancer (EOC), M2-polarized macrophage (Mø), a component of the cancer microenvironment in ascitic fluid as well as primary tumor, is thought to play an important role in cell- proliferation via paracrine activation of the STAT3 pathway. Onionin A (ONA), a natural compound purified from onions, biologically inhibits M2 polarization, and molecularly inactivates STAT3 signaling of Mø and tumor cells. Here we elucidated the indirect and direct anti-cancer effects of ONA via the STAT3 pathway. Methods: The indirect effects of ONA on EOC cells were analyzed under the co-culture system with human monocyte- derived Mø using BrdU ELISA assay. The direct effects of ONA alone and combinations with anti-cancer drugs (PTX, CBDCA, or CDDP) on proliferation and STAT3 activation of the human EOC cell lines (SKOV3, RMG1, or ES2) were evaluated using WST assay and western blot analysis. Results: M2Mø in the co-culture system enhanced proliferation of EOC cells, whereas ONA significantly reduced the enhancement of the cell-proliferation by inhibition of M2-polarization. In addition, ONA directly inhibited STAT3-activation and proliferation of EOC cells (P value < 0.01-0.05). Moreover, the suppressive effects against EOC cell proliferation were significantly increased by the combination of ONA with anti-cancer drugs (P value < 0.01-0.05). Conclusions: ONA exhibited direct anti-cancer effects in EOC as well as indirect effects by suppression of M2-polarization in co-culture system. It was suggested that the combination of ONA and anti-cancer drugs presents a new therapeutic strategy for treatment of EOC.

International Young Doctors` Session : Session 2 ; Epithelial cell adhesion molecule, a potential marker of cancer stem cells, is associated with resistance to platinum-based chemotherapy in epithelial ovarian cancer

( Shingo Tayama ),( Takeshi Motohara ),( Francisca Tjhay ),( Kiyomi Takaishi ),( Hironori Tashiro ),( Hidetaka Katabuchi ) 대한산부인과학회 2013 서울심포지움 Vol.18 No.-

Lymphadenectomy for primary ovarian cancer: a systematic review and meta-analysis

Tatsuyuki Chiyoda,Manabu Sakurai,Toyomi Satoh,Satoru Nagase,Mikio Mikami,Hidetaka Katabuchi,Daisuke Aoki 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.5

Objective: To assess the effectiveness of lymphadenectomy at primary debulking surgery(PDS) on the survival of patients with epithelial ovarian cancer (EOC). Methods: We searched PubMed, Ichushi, and the Cochrane Library. Randomized controlledtrials (RCTs) and retrospective cohort studies comparing survival of women with EOCundergoing lymphadenectomy at PDS with that of women without lymphadenectomy wereincluded. We performed a meta-analysis of overall survival (OS), progression-free survival(PFS), and adverse events. Results: For advanced-stage EOC, 2 RCTs including 1,074 women and 7 cohort studiescomprising 3,161 women were evaluated. Meta-analysis revealed that lymphadenectomy wasassociated with improved OS (hazard ratio [HR]=0.80; 95% confidence interval [CI]=0.70–0.90). However, meta-analysis of 2 RCTs revealed no significant difference in OS betweenthe lymphadenectomy and no-lymphadenectomy groups (OS: HR=1.02; 95% CI=0.85–1.22). For early-stage EOC, 1 RCT comprising 268 women and 4 cohort studies comprising 14,228women were evaluated. Meta-analysis showed that lymphadenectomy was associatedwith improved OS (HR=0.75; 95% CI=0.68–0.82). A RCT of early-stage EOC reported thatlymphadenectomy was not associated with improved OS (HR=0.85; 95% CI=0.49–1.47). Surgery-related deaths were similar in both groups (risk ratio [RR]=1.00; 95% CI=0.99–1.01);however, blood transfusion was required less frequently in the no-lymphadenectomy group(RR=0.74; 95% CI=0.63–0.86). Conclusions: Meta-analysis of RCTs and observational studies suggest thatlymphadenectomy was associated with improved OS in advanced- and early-stage EOC. However, results from RCTs demonstrate that lymphadenectomy was not associated withimproved OS in advanced- and early-stage EOC.

Clinical statistics of gynecologic cancers in Japan

Wataru Yamagami,Satoru Nagase,Fumiaki Takahashi,Kazuhiko Ino,Toru Hachisuga,Daisuke Aoki,Hidetaka Katabuchi 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.2

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve point five percent of ovarian cancer patients received neoadjuvant chemotherapy.

Opportunistic bilateral salpingectomy during benign gynecological surgery for ovarian cancer prevention: a survey of Gynecologic Oncology Committee of Japan Society of Obstetrics and Gynecology

Mikio Mikami,Satoru Nagase,Wataru Yamagami,Kimio Ushijma,Hironori Tashiro,Hidetaka Katabuchi 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.4

Objective: Recent evidence has supported the concept that epithelial ovarian cancer (EOC)arises from the cells of the fallopian tube or endometrium. This study investigated currentpractice in Japan with respect to performing opportunistic bilateral salpingectomy (OBS)during gynecological surgery for benign disease for Ovarian Cancer Prevention. Methods: We mailed a questionnaire to 767 hospitals and clinics, comprising 628 accreditedtraining institutions of the Japan Society of Obstetrics and Gynecology (JSOG), Japan Societyof Gynecologic Oncology (JSGO), or Japan Society of Gynecologic and Obstetric Endoscopyand Minimally Invasive Therapy (JSGOE) and 139 private institutions with at least one JSGOEcertifiedlicensed gynecologic laparoscopist. Results: Among the 767 institutions, 444 (57.9%) provided responses, including 91 (20.6%)that were both JSGOE and JSGO accredited, 71 (16.0%) that were only JSGO accredited, 88(19.8%) that were only JSGOE accredited, and 194 (43.7%) that were unaccredited. It wasfound that awareness and performance of OBS largely depended on the JSGO and/or JSGOEaccreditation status. OBS was only performed at 54.0% of responding institutions and just6.8% of the institutions were willing to participate in randomized controlled trials to validatethis method for reducing the incidence of ovarian cancer. Conclusion: The JSOG Gynecologic Tumor Committee will announce its opinion onsalpingectomy for ovarian cancer prevention to all JSOG members and will develop a systemfor monitoring the number of OBS procedures in Japan.

The trend and outcome of postsurgical therapy for high-risk early-stage cervical cancer with lymph node metastasis in Japan: a report from the Japan Society of Gynecologic Oncology (JSGO) guidelines evaluation committee

Masae Ikeda,Masako Shida,Shogo Shigeta,Satoru Nagase,Fumiaki Takahashi,Wataru Yamagami,Hidetaka Katabuchi,Nobuo Yaegashi,Daisuke Aoki,Mikio Mikami 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.3

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for thetreatment of cervical cancer in 2007. The aim of this research was to evaluate the influence ofthe introduction of the first guideline on clinical trends and outcomes of patients with early stage cervical cancer who underwent surgery. Methods: This analysis included 9,756 patients who were diagnosed based on thepathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b andpN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Dataof these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using acompeting risk model. Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competingrisk model for the influence of the guideline adjusted for age, year of registration, pTclassification, pN classification, histological type, and treatment methods was 1.024(p=0.864). Following the introduction of the first guideline in 2007, for patients with lymphnode metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereasthat of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). ForpN1 cases, the estimated subdistribution HR by the competing risk model for the influenceof the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapybetween CT and CCRT/RT (p=0.078). Conclusions: Survival of surgical cases was not improved by the introduction of theguidelines. It is necessary to consider more effective postsurgical therapy for high-risk early stage cervical cancer.

A retrospective study for investigating the relationship between old and new staging systems with prognosis in ovarian cancer using gynecologic cancer registry of Japan Society of Obstetrics and Gynecology (JSOG): disparity between serous carcinoma and c

Wataru Yamagami,Satoru Nagase,Fumiaki Takahashi,Kazuhiko Ino,Toru Hachisuga,Mikio Mikami,Takayuki Enomoto,Hidetaka Katabuchi,Daisuke Aoki 대한부인종양학회 2020 Journal of Gynecologic Oncology Vol.31 No.4

Objective: International Federation of Gynecology and Obstetrics (FIGO) staging for ovarian,fallopian tube, and peritoneal cancers was revised in 2014. The aim of this study is to clarifywhether the revised FIGO2014 staging reflects the prognosis of patients with ovarian cancerby histological type in Japan. Methods: We extracted 9,747 patients who were diagnosed with ovarian cancer since 2004until 2008 and who could be classified into appropriate stages from the Gynecologic CancerRegistry of Japan Society of Obstetrics and Gynecology. These cases were analyzed afterrevision to FIGO2014 based on the pTNM classification. Results: Among stage I, the 5-year overall survival rate (5y-OS) in FIGO2014 was 94.9% instage IA, 92.3% in stage IC1, 86.1% in IC2, and 84.9% in IC3 with significant differencesbetween stages IA and IC1 (p=0.012), IC1 and IC2 (p<0.001). There was a significantdifference between stages IA and IC1 in clear cell and mucinous carcinoma but not in serousand endometrioid carcinoma. Among stage III, the 5y-OS was 75.6% in stage IIIA1, 68.9% inIIIA2, 58.6% in IIIB, and 44.4% in IIIC, with significant differences between stages IIIA2 andIIIB (p=0.009), IIIB and IIIC (p<0.001). Among stage IV, the 5y-OS was 43.1% in stage IVA*and 32.1% in IVB with a significant difference (p=0.002). Conclusion: The results suggest that changes in classification for stage III and stage IVare appropriate, but the subclassification for stage IC might be too detailed. There was adiscrepancy of prognosis by histological type between stage IA and IC1.