婦人科

HPVワクチン接種による子宮頸がん検診細胞診異常例におけるハイリスクHPV感染率の変化

演　　者：: 工藤梨沙¹，関根正幸¹, 山口真奈子¹, 安達聡介¹, 八木麻美², 上田豊², 原めぐみ⁵,
Sharon Hanley⁴, 宮城悦子³, 榎本隆之¹
所属機関：: ¹新潟大学・産科婦人科, ²大阪大学・産婦人科, ³横浜市立大学・産婦人科, ⁴北海道大学・環境健康科学研究教育センター, ⁵佐賀大学・社会医学

<Background>
Human papillomavirus (HPV) vaccines have been shown to be extremely effective in prevention of infection with high-risk HPV (hrHPV). From April 2013, HPV vaccines were included in the National Immunization Program, however, only three months later, the Japanese Ministry of Health, Labour, and Welfare suspended proactive recommendations for the vaccine. In this study, we aimed to clarify the differences in the profile of hrHPV infection by HPV vaccination status in cytological abnormalities of cervical cancer screening.
<Methods>
We recruited women aged 20s-40s attending for public cervical cancer screening at Niigata city during April 2014 to March 2016. Residual Pap smear specimens were collected for hrHPV screening and genotyping test. HPV vaccination history and sexual activity were gathered from a questionnaire. The prevalence rate of each type of hrHPV infection in cytological abnormalities were compared between in HPV vaccinated and unvaccinated group. The cytological abnormality was defined as ASCUS or worse.
< Results>
The study enrolled a total of 4532 participants and included 4087 in the analysis. The cytological abnormality was found in 240 women, and HPV vaccinated and unvaccinated women were 32 (13.3%) and 208 (86.7%), respectively. The prevalence of hrHPV infection were 87.5% (28/32) and 75.0% (156/208) in vaccinated and unvaccinated group, respectively (p=0.18). The prevalence of HPV16/18 infection in vaccinated group (1/32=3.1%) was lower than that in unvaccinated group (35/208=16.8%), but the difference was not significant (p=0.059). In hrHPV-positive cases, however, the prevalence of HPV16/18 infection in vaccinated group (1/28=3.6%) was significantly lower than that in unvaccinated group (35/156=22.4%; p=0.019).
<Conclusion>
Our study demonstrated that the prevalence of HPV16/18 infection in cervical cytological abnormalities of vaccinated group was lower than that of unvaccinated group in Japan.

卵巣がんにおけるクリニカルシークエンス(Todai OncoPanel; TOP)の有効性と課題

演　　者：: 谷川道洋¹，大瀬戸久美子², 織田克利¹, 川田淑子¹, 本城晴紀¹, 稲葉洋文¹,
水野祥¹,4, 鶴賀哲史¹, 松本陽子¹, 牛久綾³, 高阪真路⁴, 油谷浩幸⁵, 間野博行⁴,
大須賀穣¹, 藤井知行¹
所属機関：: ¹東京大学・女性診療科・産科・女性外科, ²東京大学附属病院・遺伝診療部, ³東京大学附属病院・病理部, ⁴国立がん研究センター・細胞情報学, ⁵東京大学先端科学技術研究センター・ゲノムサイエンス分野

(Background)
Cancer molecular profiling is a fundamental component of precision medicine, enabling the identification of genomic alterations in genes and pathways for targeted therapy. The nation-wide infrastructure for precision medicine, such as certified sequence laboratories and knowledge databases, is urgently needed. In the University of Tokyo Hospital, an original clinical sequence assay, named Todai OncoPanel(TOP), was launched in February 2017 under the approval of ethics committee.
(Methods)
We performed TOP for 17 cases, initially diagnosed as ovarian cancer. DNA isolated from tumor tissues and matched normal peripheral blood was subjected to hybridization capture and deep-coverage NGS to detect somatic mutations, copy number alterations, and chromosomal arrangements. Germ-line variants for hereditary cancer-related genes were returned to the patients as secondary findings under the support of genetic counselors. Oncogenicity and actionability was defined for each mutation or variant.
(Results)
We obtained oncogenic gene information for all cases. As actionable information, eight somatic mutations (PI3K-AKT pathway;5, FGFR2;1, BRCA1;1, BRAF;1) were detected, and candidate molecular targeted therapies were identified. Two hypermutator cases, which is the target of immunotherapy, were detected. As secondary findings, pathogenic germ-line variants were detected in 4 cases (BRCA1;2, BRCA2;2). By multiple sampling, two cases were proven to be metastatic from endometrial cancer, not dual-primary cancers of the uterus and the ovary.
(Conclusion)
TOP may be a powerful tool for ovarian cancer to identify treatment option and to improve pathological diagnosis. As germ-line variants of hereditary cancer-related genes were detected at such high proportion, sufficient information should be given to the patients beforehand and cooperation with genetic counselors are indispensable to appropriately address the secondary findings.

早期子宮頸癌におけるセンチネルナビゲーション手術の予後および合併症に関する解析

演　　者：: 矢幡秀昭¹，貴島雅子¹, 井上修作¹, 小玉敬亮¹, 山口真一郎¹, 権丈洋徳¹, 八木裕史¹, 安永昌史¹, 大神達寛¹, 小野山一郎¹, 兼城英輔¹, 奥川馨¹, 加藤聖子¹
所属機関：: ¹九州大学・産科婦人科

Background: To evaluate the prognostic outcome and surgical complications in patients with early-stage cervical cancer who underwent sentinel node navigation surgery (SNNS) for hysterectomy or trachelectomy. Methods: A total of 139 patients who underwent SNNS using ^99mTc phytate between 2009 and 2015 were evaluated. No further lymph node dissection was performed when intraoperative analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We compared the surgical complications between the SNNS group and 67 matched patients who underwent pelvic lymph node dissection (PLND) after SLN mapping between 2003 and 2008. We also examined the clinical outcomes in the SNNS group. Results: The mean number of detected SLNs was 2.5 per patient. Fourteen of the 139 patients in the SNNS group underwent PLND based on the intraoperative SLN results. The amount of blood loss, the operative time, and the number of perioperative complications were significantly less in the SNNS group than in the matched PLND group. There was no recurrence during a follow-up period ranging from 2 to 88 months (median, 40 months) in the SNNS group. Conclusions: Using SNNS for early-stage cervical cancer is safe and effective and does not increase the recurrence rate. A future multicenter trial is warranted.

婦人科がん死亡症例大規模詳細調査ーいつまで化学療法を継続するか?(JGOG9002S試験)

演　　者：: 二神真行¹，飯野香理¹, ルイズ横田奈朋², 徳永英樹³, 戸澤晃子⁴, 横山良仁¹, 鈴木史朗⁵, 永沢崇幸⁶, 藤村正樹⁷, 青木陽一⁸, 杉山徹⁶
所属機関：: ¹弘前大学・産科婦人科, ²横浜市立大学附属病院・産科婦人科, ³東北大学・産科婦人科, ⁴聖マリアンナ医科大学・産科婦人科, ⁵名古屋大学附属病院・産科婦人科, ⁶岩手医科大学・産科婦人科, ⁷東京医科大学茨城医療センター・産科婦人科, ⁸琉球大学・産科婦人科

<Background> The authors previously reported that the median period from the last chemotherapy to death was 85 days in patients with terminal-staged gynecological cancer. The purpose of this survey was to investigate the characteristics of the cases that died from gynecological malignancies in more detail.<Methods>The medical records of the cases that died from gynecological malignancies between 2012 and 2014 were retrospectively reviewed under the approval of the Institutional Review Board of all the institutions joining this survey.
<Results>The available data from 1065 patients were accumulated from 27 institutions. The median age was 59.1 years. Primary organs were 413 (39%) of ovary, 300 (28%) of uterine cervix, 257 (24%) of endometrium, 38 (4%) of peritoneum and 57 (5%) of others. FIGO stage at an initial diagnosis was 178 (17%) of stage I, 128 (12%) of stage II, 391 (37%) of stage III and 368 (34%) of stage IV. Attending gynecological physicians suggested BSC to 81% of all dead cases. Their median survival period after suggestion of BSC was 1.8 months. Palliative chemotherapy was performed in 292 patients (27.4%). The median time from the last chemotherapy to death was 69 days in the 292 patients. Of those, 23 patients (7.9%) and 60 patients (20.6%) died within 14 and 30 days after the last chemotherapy, respectively. The number of the patients who died within 14 days after the last chemotherapy was significantly great in uterine squamous cell cervical cancers that were initially treated with surgery.
<Conclusions>The nationwide survey of the cases that died from gynecological malignancies were performed for the first time in Japan. The timing to suggest BSC may be too late because the period from suggestion of BSC to death was short. Gynecological physicians should recommend BSC earlier than usual for the patients with uterine cervical squamous cell carcinoma that initially underwent surgery, especially at terminal stage.

骨盤壁に固着した卵巣癌の摘出方法

演　　者：: 錦見恭子¹，楯真一¹, 松岡歩¹, 羽生裕二¹, 塙真輔¹, 碓井宏和¹, 三橋暁¹, 生水真紀夫¹
所属機関：: ¹千葉大学・婦人科

Objective: A complete cytoreduction of locally advanced ovarian carcinoma adhered firmly to the pelvic sidewall is not always easy to accomplish. In such case, we employed en bloc resection of the tumor along with the entire internal iliac vessel system. We examined the feasibility, safety and efficacy for prognosis of this procedure.
Material and Methods: Twenty of 249 consecutive patients with FIGO stage II-IV ovarian carcinoma at our institution between January 2008 and December 2016 had locally advanced tumors adhered firmly to the pelvic sidewall. We performed en bloc tumor resection with removal of the entire internal iliac vessel system. Surgical techniques of isolating from pelvic sidewall are as follows: (1) The obturator vessels are ligated and divided at the level of the obturator foramen. (2) Dorsal to the obturator nerve, the internal iliac vessels together with the tumor are isolated from the sacral nerve plexus and piriform muscle. During this procedure, the inferior gluteal, the internal pudendal vessels are isolated and divided. (3) The trunks of the internal iliac vessels where they bifurcate from the common iliac vessels are ligated and divided.
Results: All twenty patients successfully underwent complete cytoreduction, resulting in no gross residual tumors in the pelvic cavity. Recurrence occurred in 9 of the 20 patients with the median follow-up time of 50 months (range, 14-115 months). However, all recurrent sites were not in the pelvic sidewall. The median progression-free survival of patients was 43 months. The 5-year progression-free survival and overall survival was 49% and 71%, respectively. Mortality was none within the 90 days postoperative period. Two patients had Grade IIIb complications involving wound dehiscence and vesicovaginal fistula requiring further surgery.
Conclusion: Removal of the entire internal iliac vessel system is a feasible surgical procedure for locally advanced ovarian carcinoma adhered firmly to the pelvic sidewall.

化学療法前の好中球/リンパ球比は、進行卵巣漿液性癌のプラチナ製剤感受性に関連する

演　　者：: 川西勝¹，福田武史¹, 山内真¹, 笠井真理¹, 橋口裕紀¹, 市村友季¹, 安井智代¹, 角俊幸¹
所属機関：: ¹大阪市立大学・女性病態医学

<Objective>
We examined the correlation between neutrophil-to-lymphocyte ratio (NLR) and the sensitivity to platinum-based chemotherapy and prognosis for advanced ovarian serous carcinoma.
<Methods>
We reviewed 49 cases of ovarian serous carcinoma stage III-IV from 2005 to 2013. Cases were divided into two groups according to NLR which is calculated before initiation of platinum-based chemotherapy. The patients with high NLR of >4 were defined as the high-NLR group and the patients with low NLR of <4 were defined as the low-NLR group. We compared the characteristics, platinum sensitivity and prognosis between two groups.
<Results>
The high-NLR group contained 15 patients and the low-NLR group contained 35 patients. There was no significant difference in the patients' characteristics between two groups. 21 of 35 patients (60%) were sensitive to platinum-based chemotherapy in the low-NLR group and 4 of 15 patients (26.7%) were sensitive to platinum-based chemotherapy in the high-NLR. The low-NLR group was more sensitive to platinum-based chemotherapy than high-NLR group (p=0.031). The overall survival of the low-NLR group was significantly longer than that of the high-NLR group (p=0.022).
<Conclusion>
It is suggested that the pre-chemotherapeutical NLR might be associated with sensitivity to platinum-based chemotherapy and predictor of prognosis of advanced ovarian serous carcinoma.

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