研究者詳細 - 山上　亘

論文 - 山上　亘

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A retrospective study for investigating the outcomes of endometrial cancer treated with radiotherapy

Sakai K., Yamagami W., Machida H., Ebina Y., Kobayashi Y., Tabata T., Kaneuchi M., Nagase S., Enomoto T., Aoki D., Mikami M.

International Journal of Gynecology and Obstetrics （International Journal of Gynecology and Obstetrics） 156 （ 2 ） 262 - 269 2022年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00207292

Objective: To clarify the role of radiotherapy for endometrial cancer. Methods: Data were analyzed for 39 247 patients with endometrial cancer registered with the Gynecologic Cancer Registry of the Japan Society of Obstetrics and Gynecology from 2004 to 2011. Results: The rates of 5-year overall survival (5y-OS) in the radiotherapy and surgery groups were 53.6% and 94.5% in stage I or II, and 15.5% and 67.5% in stage III or IV, respectively. The prognosis in the radiotherapy group was significantly poorer than that in the surgery group. In multivariate analysis, age, advanced stage, histological type, risk of recurrence, and initial radiotherapy were independent prognostic factors. The rates of 5y-OS with no adjuvant therapy, adjuvant chemotherapy, and adjuvant radiotherapy were 95.3%, 92.9%, and 87.1% for stage I or II, respectively, with significant differences among all groups (P < 0.001), and 60.0%, 70.4%, and 55.5% for stage III or IV, respectively, with significant differences of adjuvant chemotherapy with no adjuvant therapy (P < 0.001) and with adjuvant radiotherapy (P < 0.001). In multivariate analysis, age, advanced stage, histological type, lymphadenectomy, and adjuvant radiotherapy were independent prognostic factors. Conclusion: Patients treated with radiotherapy had a significantly poorer prognosis and the appropriate indication of radiotherapy for endometrial cancer requires further study.

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Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual Patient Report for 2018 and Annual Treatment Report for 2013

Nagase S., Ohta T., Takahashi F., Yamagami W., Yaegashi N., Enomoto T., Katabuchi H., Kawana K., Kobayashi H., Kobayashi Y., Shozu M., Baba T., Morishige K., Yoshida Y., Yoshino K., Tokunaga H.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research） 48 （ 3 ） 541 - 552 2022年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13418076

To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2018 and the Annual Treatment Report for 2013, on the outcomes of patients who started treatment in 2013. The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2018 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2013 was analyzed by using the Kaplan–Meier, log-rank, and Wilcoxson tests. Treatment was initiated in 2018 for 7304 patients with cervical cancer; 11 230 with endometrial cancer; 7031 with ovarian, tubal, and peritoneal cancer; 2072 with ovarian borderline tumors; and with the others (222 vulvar cancer, 159 vaginal cancer, 413 uterine sarcoma, 54 uterine adenosarcoma, and 135 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5-year survival rates of the patients with cervical cancer were 93.1%, 75.9%, 59.1%, and 31.2% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.1%, 89.2%, 73.6%, and 25.8% for Stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 89.7%, 76.8%, 49.1%, and 32.4% for Stages I, II, III, and IV, respectively. The annual report is important to provide knowledge on gynecological malignancy trends in Japan.

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Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study

Machida H., Matsuo K., Oba K., Aoki D., Enomoto T., Okamoto A., Katabuchi H., Nagase S., Mandai M., Yaegashi N., Yamagami W., Mikami M.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 33 （ 1 ） e3 2022年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2005-0380

Objective: Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined. Methods: The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks. Results: Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high-(≥50, ≥51, and ≥27), moderate-(20–49, 20–50, and 17–26), and low-volume centers (≤19, ≤19, and ≤16) by cases/ year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78–0.88; aHR=0.78, 95% CI=0.75–0.83; and aHR=0.90, 95% CI=0.86–0.95 for endometrial, cervical, and ovarian tumors). Conclusion: Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

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Characteristics and clinicopathological features of patients with ovarian metastasis of endometrial cancer: a retrospective study

Matoba Y., Yamagami W., Chiyoda T., Kobayashi Y., Tominaga E., Banno K., Aoki D.

Journal of Obstetrics and Gynaecology （Journal of Obstetrics and Gynaecology） 42 （ 6 ） 2456 - 2462 2022年

ISSN 01443615

There are no criteria for patient selection for ovarian-preserving surgery for endometrial cancer (EC). In this study, intraoperative findings of ovarian swelling (OvS) and the clinicopathological features of patients with EC with or without ovarian metastasis were analysed to identify risk factors for ovarian metastasis. Patients who underwent surgery for EC between 2012 and 2019 at our hospital were enrolled. In univariate analysis, all features were significantly higher in metastasis(+) cases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and OvS were significant risk factors. In univariate analysis in stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly higher in metastasis(+) cases. LSI, CSI, and OvS were significant risk factors in multivariate analysis. Patients with type 1 histologic type EC without myometrial invasion ≥1/2, CSI and extrauterine lesions are appropriate for ovarian preservation. IMPACT STATEMENTWhat is already known on this subject? The number of premenopausal patients with endometrial cancer (EC) is increasing. Bilateral oophorectomy for EC results in surgical primary ovarian insufficiency, and thus, surgery with ovarian preservation has been examined. However, there are few reports on risk factors for ovarian metastasis of EC and no established criteria for patient background or pathological factors to determine suitability for ovarian preservation surgery. What do the results of this study add? In univariate analysis, all pathological findings suggestive of disease progression were more frequent in cases with ovarian metastases. In multivariate analysis, lymphatic space invasion (LSI), cervical stromal involvement (CSI), peritoneal dissemination, and ovarian swelling (OvS) were identified as significant risk factors for ovarian metastasis. In an analysis of stage I and II cases classified without adnexal pathological factors, type 2 histologic type, LSI, CSI, and OvS were significantly more common in cases with ovarian metastasis, and LSI, CSI, and OvS emerged as significant risk factors for ovarian metastasis in multivariate analysis. What are the implications of these findings for clinical practice and/or further research? Patients with type 1 histologic type EC without depth of myometrial invasion ≥1/2, CSI, or extrauterine lesions may be appropriate cases for ovarian preservation.

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Clinical Usefulness of Endometrial Cytology in Determining the Therapeutic Effect of Fertility Preserving Therapy

Yoshimura T., Yamagami W., Takahashi M., Hirano T., Sakai K., Makabe T., Chiyoda T., Banno K., Aoki D.

Acta Cytologica （Acta Cytologica） 66 （ 2 ） 1 - 8 2021年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00015547

Introduction: The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy. Methods: Overall, 77 patients who underwent dilatation and curettage (D&C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients' medical records. Results: The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&C being the gold standard for diagnosis in 142 D&C/cytological examinations. Among patients with no residual disease on D&C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&C and cytology. Discussion/Conclusion: The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&C during MPA therapy had a low clinical significance.

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Comparison of treatment outcomes of surgery and radiotherapy, including concurrent chemoradiotherapy for stage Ib2-IIb cervical adenocarcinoma patients: a retrospective study

Kondo E., Yoshida K., Tabata T., Kobayashi Y., Yamagami W., Ebina Y., Kaneuchi M., Nagase S., Machida H., Mikami M.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 33 （ 2 ） e14 2021年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 20050380

Objective: The study compared the treatment outcomes of surgery versus radiotherapy, including concurrent chemoradiotherapy, in stage Ib2–IIb cervical adenocarcinoma patients in Japan. Methods: Of 57,470 patients diagnosed with stage I–IV cervical cancer from January 2001– December 2011, 1,932 patients with stage Ib2–IIb cervical adenocarcinoma were initially treated by surgery or radiotherapy. The primary endpoint was 5-year overall survival (OS) in all and 614 propensity score-matched (PSM) patients (307 per group). We compared OS and prognosis factors based on age, primary stage, and treatment arm. Results: In Japan, >80% (n=1,573) of stage Ib2–IIb cervical adenocarcinoma patients underwent surgery. The 5-year OS of surgery vs. radiotherapy groups were 82.1% (n=704) vs. 79.7% (n=59) (hazard ratio [HR]=1.494; 95% confidence interval [CI]=0.826–2.702; p=0.181) for stage Ib2, 76.6% (n=239) vs. 66.7% (n=54) (HR=1.679; 95% CI=0.986–2.858; p=0.053) for stage IIa, and 71.1% (n=630) vs. 58.9% (n=246) (HR=1.711; 95% CI=1.341–2.184; p<0.001) for stage IIb. In 614 PSM patients balanced for age and carcinoma stage Ib2–IIb, the 5-year OS of surgery vs. radiation groups was 73.0% (n=307) vs. 65.5% (n=307) (HR=1.394; 95% CI=1.044–1.860; p=0.023). In multivariable analysis, age (HR=1.293; 95% CI=1.045–1.601; p=0.018), treatment arm, radiotherapy (HR=1.556; 95% CI=1.253–1.933; p<0.001), and stage IIb (HR=1.783; 95% CI=1.443–2.203; p=0.018) were independent prognosis factors for 5-year OS in stage Ib2–IIb adenocarcinoma patients. Conclusion: Age (>65 years), treatment arm (radiotherapy), and stage IIb significantly affect OS in cervical adenocarcinoma patients. Surgery may be considered for <65-year-old patients with stage IIb adenocarcinoma.

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Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan

Ohta T., Nagase S., Okui Y., Enomoto T., Yamagami W., Mikami M., Tokunaga H., Ino K., Ushijima K., Shozu M., Tashiro H., Mandai M., Miyamoto S., Morishige K.I., Yoshida Y., Yoshino K., Saito T., Kobayashi E., Kobayashi H., Takekuma M., Terai Y., Fujii T., Kanao H., Aoki D., Katabuchi H., Yaegashi N.

International Journal of Clinical Oncology 26 （ 12 ） 2318 - 2330 2021年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13419625

Objective: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. Methods: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients’ characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. Results: The median patient age was 44 (20–80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49–51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. Conclusion: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

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Hysteroscopic treatment assisted by photodynamic diagnosis for atypical polypoid adenomyoma: A report of two cases

Matoba Y., Banno K., Kobayashi Y., Yamagami W., Nakamura M., Kisu I., Aoki D.

Photodiagnosis and Photodynamic Therapy 36 102583 2021年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 15721000

Atypical polypoid adenomyoma (APA) is an intrauterine tumor for which hysteroscopic tumor resection allows for fertility preservation. Complete resection is important because of the high recurrence rate of APA, but is difficult due to the lack of characteristic hysteroscopic findings. We previously reported a case in which photodynamic diagnosis (PDD) was useful for detection of APA. Here, we report two additional cases of APA treated by hysteroscopic resection with PDD. The procedure was approved by the ethical committee. Case 1: A 35-year-old female who underwent hysteroscopic surgery for a submucosal tumor suspected to be APA with hypermenorrhea. Case 2: A 37-year-old female in whom hysteroscopic surgery was performed for a residual APA lesion after hormone therapy. In Case 1, PDD identified the tumor borders and this enabled as complete resection as possible. In Case 2, lesions could not be identified clearly under white light, but some areas were PDD-positive and were excised. Among 19 specimens from these two cases and the previously reported case, all PDD-positive specimens were pathologically diagnosed as APA. The sensitivity and specificity of PDD for APA were 76.9% and 100%, respectively. These results suggest that PDD can contribute to identification of APA.

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Clinicopathological characteristics and prognostic factors of ovarian granulosa cell tumors: A JSGO-JSOG joint study

Ebina Y., Yamagami W., Kobayashi Y., Tabata T., Kaneuchi M., Nagase S., Enomoto T., Mikami M.

Gynecologic Oncology 163 （ 2 ） 269 - 273 2021年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00908258

Objectives: The aim of this study was to elucidate the clinicopathological features of ovarian granulosa cell tumors (GCTs) and to identify the prognostic factors. Methods: The Japanese Society of Gynecologic Oncology (JSGO) conducted an observational retrospective cohort study of women with GCTs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology (JSOG) between 2002 and 2015. Clinicopathological features, including lymph node metastasis, were evaluated. In addition, we performed a prognostic analysis of patients between 2002 and 2011 for whom survival data were available. Kaplan–Meier and multivariate Cox proportional hazards analyses were performed. Results: We identified 1426 patients with GCTs. Of the 222 patients who underwent lymph node dissection, 10 (4.5%) had lymph node metastasis. The incidence of lymph node metastasis in patients with pT1, pT2, and pT3 was 2.1%, 13.3%, and 26.7%, respectively (p < 0.001). Prognostic analysis was performed on 674 patients. In the multivariate Cox regression analysis, residual disease after initial surgery (hazard ratio (HR) = 10.39, 95% confidence interval (CI) = 3.15–34.29) and lymph node metastasis (HR = 5.58, 95% CI = 1.62–19.19) were independent risk factors for cancer-specific survival. Conclusions: In the initial surgery for GCTs, lymph node dissection can be omitted if the operative finding is pT1. In cases of pT2 or higher, lymph node dissection should be considered. Debulking is critical for achieving no gross residual tumor at the end of the surgery.

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Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40 years or younger

Makabe T., Yamagami W., Hirasawa A., Miyabe I., Wakatsuki T., Kikuchi M., Takahashi A., Noda J., Yamamoto G., Aoki D., Akagi K.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 26 （ 9 ） 1767 - 1774 2021年10月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13419625

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients. [Methods] Sixty-five patients aged 40 years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells. [Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3’ untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35. [Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40 years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

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Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian, fallopian tube, and primary peritoneal cancer patients

Iwasa-Inoue N., Nomura H., Kataoka F., Chiyoda T., Yoshihama T., Nanki Y., Sakai K., Kobayashi Y., Yamagami W., Morisada T., Hirasawa A., Aoki D.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 27 （ 2 ） 441 - 447 2021年10月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13419625

Background: This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian, fallopian tube, and primary peritoneal cancer patients in the neoadjuvant setting. Methods: Ovarian, fallopian tube or primary peritoneal cancer patients with stage III–IV disease received neoadjuvant chemotherapy (NAC) every 3 weeks consisting of paclitaxel (80 mg/m2) on days 1, 8, and 15; carboplatin (AUC 6.0 mg/mL × min.) on day 1; and bevacizumab (15 mg/kg) on day 1. Interval debulking surgery (IDS) was performed after 3 cycles of dose-dense TC-bevacizumab therapy. The primary endpoint was the rate of complete resection by IDS. Secondary endpoints were treatment completion rate, treatment exposure, response rate to NAC, adverse events, and perioperative complications. Results: Twenty-four patients were included in this study. The median age was 55.5 years (37–80 years), and most patients had high-grade serous carcinoma accounted (n = 18). IDS was performed in all patients with complete resection achieved in 75% (95% confidence interval: 57.7–92.3%). The lower limit exceeded the preset threshold rate of 55%. The response rate to NAC was 79%, and serum CA125 levels were in the normal range after NAC in 57% of patients. Grade 4 hematological toxicities and grade 3/4 non-hematological toxicities occurred in 29% and 17% of patients during NAC, respectively. Grade 3/4 perioperative complications were seen in 29% of patients, but no gastrointestinal perforations or treatment-related deaths occurred. Conclusions: Neoadjuvant dose-dense TC-bevacizumab therapy was well tolerated, and a satisfactory rate of complete resection by IDS was achieved.

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ARID1A mutation/ARID1A loss is associated with a high immunogenic profile in clear cell ovarian cancer

Kuroda Y., Chiyoda T., Kawaida M., Nakamura K., Aimono E., Yoshimura T., Takahashi M., Saotome K., Yoshihama T., Iwasa N., Sakai K., Yamagami W., Nishihara H., Aoki D.

Gynecologic Oncology 162 （ 3 ） 679 - 685 2021年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00908258

Objectives: ARID1A mutation is frequently found in clear cell ovarian cancer (CCC) and endometrioid ovarian cancer (EC). Anti-PD-1 monotherapy has been found to have limited efficacy in epithelial ovarian cancer; however, anti-PD-1 therapy showed significant clinical benefit in some CCC. We sought to define the relationship of ARID1A mutation/ARID1A expression to the immunogenic profile of different histologic subtypes of ovarian cancer. Methods: We performed next-generation sequencing of 160 cancer-related genes. Also, we analyzed the immunohistochemical status of ARID1A, PD-L1, and CD8 with survival in different histologic subtypes of ovarian cancer in a total of 103 cases. Results: ARID1A mutation was found in 0% of the high-grade serous ovarian cancer (HGSC) (n = 36), 41.5% of the CCC (n = 41), 45.0% of the EC (n = 20), and 33.3% of the mucinous ovarian cancer (MC) (n = 6) cases. ARID1A loss was found in 19.4% of the HGSC, 75.6% of the CCC, 60.0% of the EC and 0% of the MC cases. ARID1A mutation was found to be associated with high PD-L1 (p < 0.001) or CD8 levels (p < 0.001) in CCC but not in other histologic subtypes. Meanwhile, ARID1A loss was associated with high PD-L1 or CD8 levels in CCC (p < 0.001) and HGSC (p < 0.001) but not in EC and MC. In addition, ARID1A mutation was associated with high tumor mutation burden in CCC (p = 0.006). Conclusions: ARID1A mutation/ARID1A expression is associated with immune microenvironmental factors in CCC but not in EC. ARID1A status can be a biomarker for selecting candidates for immune checkpoint blockade in CCC.

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当院で経験した子宮体部大細胞神経内分泌癌(LCNEC)の3例

平松真生子, 山上亘, 平野卓朗, 吉村拓馬, 千代田達幸, 西尾浩, 仲村勝, 阪埜浩司, 田中守, 青木大輔

東京産科婦人科学会会誌 70 （ 3 ） 493 - 497 2021年07月

研究論文（学術雑誌）, 共著, 査読有り

Evaluating the importance of routine drainage following laparoscopic pelvic lymph node dissection for gynecological malignancies

Sakai K, Nakamura M, Yamagami W, Chiyoda T, Kobayashi Y, Nishio H, Hayashi S, Nomura H, Kataoka F, Tominaga E, Banno K, Aoki D

Int J Gynaecol Obstet 153 （ 3 ） 438 - 442 2021年06月

研究論文（学術雑誌）, 共著, 査読有り

Survey of the clinical practice pattern of using sentinel lymph node biopsy in patients with gynecological cancers in Japan: the Japan Society of Gynecologic Oncology study

Togami S., Kobayashi H., Niikura H., Shimada M., Susumu N., Tanaka T., Terai Y., Nagai T., Baba T., Yahata H., Yamagami W., Yamaguchi K., Yamashita T., Yaegashi N., Katabuchi H., Aoki D.

International Journal of Clinical Oncology （International Journal of Clinical Oncology） 26 （ 5 ） 971 - 979 2021年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13419625

Background: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan. Methods: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities’ experience with clinical research on SN biopsy. Results: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%). Conclusion: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.

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Annual report of the Committee on Gynecologic Oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2017 and annual treatment report for 2012

Nagase S., Ohta T., Takahashi F., Yaegashi N., Enomoto T., Katabuchi H., Kawana K., Kobayashi H., Kobayashi Y., Shozu M., Baba T., Morishige K., Yoshida Y., Yoshino K., Yamagami W., Tokunaga H.

Journal of Obstetrics and Gynaecology Research 47 （ 5 ） 1631 - 1642 2021年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 13418076

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012. Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests. Results: Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively. Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

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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

Ikeda M., Shida M., Shigeta S., Nagase S., Takahashi F., Yamagami W., Katabuchi H., Yaegashi N., Aoki D., Mikami M.

Journal of Gynecologic Oncology （Journal of Gynecologic Oncology） 32 （ 3 ） e44 2021年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 20050380

Objective: The Japan Society of Gynecologic Oncology published the first guidelines for the treatment of cervical cancer in 2007. The aim of this research was to evaluate the influence of the 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 the pathological Tumor-Node-Metastasis (pTNM) classification (i.e., pT1b1, pT1b2, pT2b and pN0, pN1, pNX) and received surgery as a primary treatment between 2004 and 2009. Data of these patients were retrospectively reviewed, and clinicopathological trends were assessed. The influence of the introduction of the guideline on survival was determined by using a competing risk model. Results: For surgery cases, the estimated subdistribution hazard ratio (HR) by the competing risk model for the influence of the guideline adjusted for age, year of registration, pT classification, 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 lymph node metastasis, the use of chemotherapy (CT) as a postsurgical therapy increased, whereas that of concurrent chemoradiotherapy (CCRT)/radiotherapy (RT) decreased (p<0.010). For pN1 cases, the estimated subdistribution HR by the competing risk model for the influence of the guideline was 1.094 (p=0.634). There was no significance in the postsurgical therapy between CT and CCRT/RT (p=0.078). Conclusions: Survival of surgical cases was not improved by the introduction of the guidelines. It is necessary to consider more effective postsurgical therapy for high-risk early-stage cervical cancer.

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Atypical vessels in hysteroscopy: Usefulness in prediction of malignant diseases in patients treated with tamoxifen

Oka E., Sakai K., Yamagami W., Hirano T., Makabe T., Yoshihama T., Chiyoda T., Kataoka F., Banno K., Aoki D.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research） 47 （ 4 ） 1510 - 1515 2021年04月

研究論文（学術雑誌）, 査読有り, ISSN 1341-8076

Aim: Tamoxifen (TAM) is widely used in adjuvant endocrine therapy for invasive breast cancer as a selective estrogen modulator, but this treatment has a risk of developing endometrial malignancy. However, hysteroscopic findings during or after TAM treatment are unclear. The aim of this study is to examine the association between hysteroscopic patterns and malignant histological findings during or after treatment with TAM. Methods: The subjects were patients who received TAM after surgery for breast cancer and underwent hysteroscopy at our institution from January 2016 to December 2019. Clinicopathological factors and hysteroscopic findings were collected from medical records and investigated retrospectively. Histologically, atypical endometrial hyperplasia, endometrial cancer, and carcinosarcoma were classified as malignant diseases. Results: A total of 26 patients were eligible for the study. Hysteroscopic findings included an irregular surface of the endometrium (n = 3, 11.5%), atypical vessels (n = 10, 38.5%), papillary structure (n = 3, 11.5%), and polypoid structure (n = 18, 69.2%). Histological examination revealed malignancy in six patients (23.0%). The percentage of atypical vessels in patients with malignancies was significantly higher than that in patients with a normal endometrium or benign lesion (100% vs. 20%, p = 0.0009). The sensitivity and specificity of atypical vessels in hysteroscopy for diagnosis of malignant diseases were 100% and 80%, respectively. Conclusions: Hysteroscopic findings of atypical vessels may be useful for prediction of malignant diseases in patients treated with TAM.

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術前診断は子宮体癌であったが、子宮摘出検体で絨毛癌の確定診断に至った1例

吉村拓馬, 山上亘, 川井田みほ, 平野卓朗, 坂井健良, 真壁健, 千代田達幸, 小林佑介, 片岡史夫, 阪埜浩司, 亀山香織, 青木大輔

日本婦人科病理学会誌 11 （ 1 ） 39 - 44 2021年03月

研究論文（学術雑誌）, 共著, 査読有り

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome.

Yoshihama T, Hirasawa A, Sugano K, Yoshida T, Ushiama M, Ueki A, Akahane T, Nanki Y, Sakai K, Makabe T, Yamagami W, Susumu N, Kameyama K, Kosaki K, Aoki D

International cancer conference journal 10 （ 1 ） 6 - 10 2021年01月

研究論文（学術雑誌）, 共著, 査読有り

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