Faculty Profiles - NAKAMURA Keiichiro

Papers - NAKAMURA Keiichiro

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産官学協働の地域モデルと高齢女性へのホルモン補充療法を用いた臨床研究がもたらす意義

三苫智裕, 牧尉太, 谷和祐, 樫野千明, 依田尚之, 光井崇, 鎌田泰彦, 中村圭一郎, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 158 - 158 2022.10

Barbed sutureによる2層連続縫合は帝王切開による子宮創の菲薄化を予防する

牧尉太, 三苫智裕, 樫野千明, 依田尚之, 光井崇, 衛藤英理子, 中村圭一郎, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 112 - 112 2022.10

産官学協働の地域モデルと高齢女性へのホルモン補充療法を用いた臨床研究がもたらす意義

三苫智裕, 牧尉太, 谷和祐, 樫野千明, 依田尚之, 光井崇, 鎌田泰彦, 中村圭一郎, 増山寿

日本女性医学学会雑誌 30 ( 1 ) 158 - 158 2022.10

Tumor size before image-guided brachytherapy is an important factor of local control after radiotherapy for cervical squamous cell carcinoma: analysis in cases using central shielding. International journal

Kotaro Yoshio, Hiroki Ihara, Kazuhiro Okamoto, Etsuji Suzuki, Takeshi Ogata, Soichi Sugiyama, Keiichiro Nakamura, Shoji Nagao, Hisashi Masuyama, Takao Hiraki

Journal of radiation research 63 ( 5 ) 772 - 779 2022.9

Language：English Publishing type：Research paper (scientific journal)

We analyzed the local control (LC) of cervical squamous cell carcinoma treated by computed tomography (CT)-based image-guided brachytherapy (IGBT) using central shielding (CS). We also examined the value of tumor diameter before brachytherapy (BT) as a factor of LC. In total, 97 patients were analyzed between April 2016 and March 2020. Whole-pelvic (WP) radiotherapy (RT) with CS was performed, and the total pelvic sidewall dose was 50 or 50.4 Gy; IGBT was delivered in 3-4 fractions. The total dose was calculated as the biologically equivalent dose in 2 Gy fractions, and distribution was modified manually by graphical optimization. The median follow-up period was 31.8 months (6.3-63.2 months). The 1- and 2-year LC rates were 89% and 87%, respectively. The hazard ratio was 10.11 (95% confidence interval: 1.48-68.99) for local recurrence in those with a horizontal tumor diameter ≥ 4 cm compared to those with < 4 cm before BT. In CT-based IGBT for squamous cell carcinoma, favorable LC can be obtained in patients with a tumor diameter < 4 cm before BT. However, if the tumor diameter is ≥ 4 cm, different treatment strategies such as employing interstitial-BT for dose escalation may be necessary.

DOI： 10.1093/jrr/rrac040

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Molecular Characteristics of Metastatic Lesions Have Superior Prognostic Impact on Endometrial Cancer. International journal

Kazuhiro Okamoto, Keiichiro Nakamura, Junko Haraga, Hisashi Masuyama

Anticancer research 42 ( 9 ) 4535 - 4543 2022.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: In endometrial cancer (EC), lymph node (LN) metastasis significantly impacts prognosis. Thus far, no studies have reported the molecular genetics of each metastatic lesion. This study aimed to investigate the molecular characteristics of primary and metastatic LNs and their association with clinical outcomes. PATIENTS AND METHODS: The clinicopathological and molecular characteristics of 33 patients with EC with regional LN metastasis (FIGO stage IIIC) were investigated; we evaluated the mutational status of p53 and DNA mismatch repair (MMR) proteins in the primary lesion, all the positive LNs (102 lesions), mutational variation between primary and paired metastatic lesions, inter-lesion heterogeneity, and their association with clinical outcomes. RESULTS: Immunohistochemically, 12 patients (36.4%) displayed aberrant p53 expression in metastatic lesions, and a concordant rate of 93.4% was observed between primary and metastatic lesions. Inter-lesion heterogeneity was observed in 20 cases (60.6%). In Kaplan-Meier analysis, patients with aberrant p53 expression in metastatic LNs exhibited worse progression-free survival (PFS) than those with wild-type p53 expression (p=0.008). Wild-type p53 expression in primary lesion with inter-lesion heterogeneity had a significantly worse PFS (p=0.049) than those without heterogeneity. In the Cox univariate analysis, p53 expression in metastatic LNs was significantly associated with recurrence (p=0.013). Genetic diversity between primary and metastatic lesions and among metastases was validated by evaluating the p53 and MMR proteins using immunohistochemistry analysis. CONCLUSION: The molecular characteristics of metastatic lesions in addition to those of primary lesions could provide beneficial prognostic information in patients with EC with regional LN metastasis.

DOI： 10.21873/anticanres.15956

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腫瘍の自然脱落により診断に至った子宮腺肉腫の一例

田中佑衣, 依田尚之, 兼森雅敏, 白河伸介, 岡本和浩, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 71 ( Suppl. ) S62 - S63 2022.9

Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia†. International journal

Iwao Kukimoto, Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Yoichi Aoki, Harushige Yokota, Katsuyuki Konnai, Ai Nio, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Muneaki Shimada, Hidekatsu Nakai, Hiroyuki Yoshida, Takeshi Motohara, Hiroyuki Yamazaki, Keiichiro Nakamura, Asuka Okunomiya, Nobutaka Tasaka, Mitsuya Ishikawa, Yasuyuki Hirashima, Yuko Shimoji, Mayuyo Mori, Takashi Iwata, Fumiaki Takahashi, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Japanese journal of clinical oncology 52 ( 10 ) 1242 - 1247 2022.8

Language：English Publishing type：Research paper (scientific journal)

Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan. The risk of cervical intraepithelial neoplasia progression was assessed by calculating a prevalence ratio of each human papillomavirus type for cervical intraepithelial neoplasia grade 2/3 versus grade 1. Among the human papillomavirus types studied, human papillomavirus 52 was detected significantly more frequently in western hospitals than in eastern hospitals in cervical intraepithelial neoplasia grade 1 patients, but was less frequent in cervical intraepithelial neoplasia grade 2/3. The prevalence of particular human papillomavirus types was not significantly different between patients in hospitals in eastern Japan and those in hospitals in western Japan for invasive cervical cancer. In both eastern and western hospitals, a higher risk of cervical intraepithelial neoplasia progression was observed in patients infected with human papillomavirus 16, 31 or 58. In contrast, there was a significantly higher prevalence of human papillomavirus 52 infection in women with cervical intraepithelial neoplasia grade 2/3 than in those with cervical intraepithelial neoplasia grade 1 in eastern hospitals (prevalence ratio, 1.93; 95% confidence interval, 1.48-2.58), but not in western hospitals (prevalence ratio, 1.03; 95% confidence interval, 0.83-1.30). Regional differences of human papillomavirus 52 prevalence in cervical intraepithelial neoplasia lesions may exist and emphasize the importance of continuous monitoring of human papillomavirus type prevalence throughout the country in order to accurately assess the efficacy of human papillomavirus vaccines.

DOI： 10.1093/jjco/hyac127

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Liquid Biopsy Revealed HBOC Pedigree and Led to Medical Management Among the Relatives.

Chikako Ogawa, Akira Hirasawa, Reimi Sogawa, Kayoko Hasuoka, Shuta Tomida, Mashu Futagawa, Yusaku Urakawa, Mariko Kochi, Hideki Yamamoto, Keiichiro Nakamura, Hisashi Masuyama

Acta medica Okayama 76 ( 4 ) 479 - 483 2022.8

Language：English

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.

DOI： 10.18926/AMO/63908

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当院で施行した婦人科癌のがんゲノム医療の現況と課題

依田尚之, 小川千加子, 入江恭平, 岡本和浩, 松岡敬典, 久保光太郎, 中村圭一郎, 長尾昌二, 増山寿, 平沢晃

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 205 - 205 2022.7

卵巣未熟奇形種に併発した抗NMDA受容体脳炎の一例

松岡敬典, 白河伸介, 岡本和浩, 依田尚之, 久保光太郎, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 285 - 285 2022.7

当院で施行した婦人科癌のがんゲノム医療の現況と課題

依田尚之, 小川千加子, 入江恭平, 岡本和浩, 松岡敬典, 久保光太郎, 中村圭一郎, 長尾昌二, 増山寿, 平沢晃

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 205 - 205 2022.7

肥満を伴う子宮体癌患者に対して腹腔鏡下手術を施行した2症例

久保光太郎, 岡本和浩, 依田尚之, 松岡敬典, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 244 - 244 2022.7

Abscopal effectによる遠隔転移の消失と考えられた子宮癌肉腫の一例

岡本和浩, 入江恭平, 松岡敬典, 依田尚之, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 64回 237 - 237 2022.7

ADAR1 and AZIN1 RNA editing function as an oncogene and contributes to immortalization in endometrial cancer. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Kazuhiro Okamoto, Hirofumi Matsuoka, Hisashi Masuyama

Gynecologic oncology 166 ( 2 ) 326 - 333 2022.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. However, its functional role and clinical significance in endometrial cancer (EC) remain unclear. METHODS: Adenosine Deaminase family Acting on RNA1 (ADAR1) expression and Antizyme inhibitor 1 (AZIN1) RNA editing were examined to clarify the correlation with clinicopathological parameters and prognosis in EC patients. The biological functions and inhibitory effects of ADAR1 knockdown were investigated in JHUCS-1 and TU-ECS-1 EC cell lines. RESULTS: ADAR1 showed significant association with worse histology (P = 0.006), and lymph vascular space involvement (P = 0.049) in EC. The level of AZIN1 RNA editing was also significantly associated with worse histology (P = 0.012). ADAR1 expression was significantly correlated with AZIN1 RNA editing level (R = 0.729, R2 = 0.547, P < 0.001). Multivariate analysis indicated that higher ADAR1 expression along with AZIN1 RNA editing is an independent predictor of prognosis in EC patients (P = 0.015). Knockdown of ADAR1 led to increased MDA-5, RIG-I, PKR, and IRF-7 expression, which in turn resulted in increased levels of Bak and apoptosis in EC cells. CONCLUSIONS: High ADAR1 expression along with AZIN1 RNA editing could be a predictor of worse prognosis in EC. ADAR1 could be a potential therapeutic target in EC patients.

DOI： 10.1016/j.ygyno.2022.05.026

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高齢者に発症した排尿障害を伴う陰唇癒着症の1例

西田康平, 岡本和浩, 入江恭平, 松岡敬典, 依田尚之, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 70 ( 2 ) 273 - 276 2022.6

Language：Japanese Publisher：中国四国産科婦人科学会

陰唇癒着症は左右の小陰唇または大陰唇が癒着している状態であり、低エストロゲン状態を背景に脆弱となった外陰部へ機械的刺激や炎症などが起こり、それらが誘因となり陰唇内面同士に癒着が生じるものである。今回、排尿障害を契機に診断された陰唇癒着症の一例を経験したので文献的考察を踏まえて報告する。症例は79歳、1妊1産、排尿障害を主訴に前医を受診され、陰唇癒着症の診断にて当院に紹介となった。外陰部は左右の陰唇が完全に癒着しており、会陰部に尿の流出路と思われるピンホール状の孔を認めた。骨盤造影MRI検査を施行し、泌尿生殖器の解剖学的な異常はなく、T2強調画像にて、外尿道口から外陰部正中に向かう尿の流出路と思われる線上の高信号域、また外陰部正中に尿の貯留と思われる嚢胞状の領域を認めた。排尿障害を伴う陰唇癒着症の診断にて外陰部癒着剥離術を行う方針となった。脊椎麻酔下に、ピンホール状の孔を基点として鋭的鈍的に孔を拡張し、腟、本来の尿道口を確認、陰唇の間を覆っている外陰部の皮膚様の組織を陰核付近まで切開し、癒着を剥離した。大陰唇の皮膚と小陰唇の内側の粘膜面を再癒着防止のために全周性に縫合し、手術を終了した。術後経過は良好で術後2日目に退院となった。退院2週間後の外来再診時に創部に異常なく全抜糸した。前医での週2回の創部洗浄、エストロゲン含有ゲルの塗布を指示し、経過観察とした。術後2ヵ月の外来再診時に再癒着なきことを確認し、終診とした。高齢者の陰唇癒着症は報告例も少なく、明確な治療指針は示されていない。陰唇癒着症の症状は様々であるが、排尿障害、尿失禁を主訴とする高齢女性を診察する際には陰唇癒着症も鑑別に挙げ、外陰部の診察を行い、陰唇癒着症の場合には適切な介入を行う必要がある。(著者抄録)

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卵巣癌のSister Mary Joseph's noduleに対して臍切除を行った3例

小川麻理子, 依田尚之, 入江恭平, 岡本和浩, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

現代産婦人科 70 ( 2 ) 409 - 415 2022.6

Language：Japanese Publisher：中国四国産科婦人科学会

Sister Mary Joseph's nodule(SMJN)は腹腔内または骨盤の悪性腫瘍の臍転移であり、1-3%と稀である。SMJNの転移経路は腹膜播種からの転移が90%以上といわれているが、術中所見で腹膜播種を伴わない卵巣癌のSMJNの3例を経験したので報告する。症例1は75歳女性。卵巣癌IVB期(pT1cN0M1、類内膜癌)に対し単純子宮全摘出術(TAH)+両側付属器摘出術(BSO)+大網部分切除術(pOMT)+臍切除を施行しComplete surgeryが完遂できた。術後補助化学療法としてtri-weekly Paclitaxel+Carboplatin(tri-TC)+Bevacizmabを8サイクル施行後、Bevacizmabの維持療法を行い現在再発はない。症例2は74歳女性。卵巣癌IVB期(pT1aN0M1、類内膜癌)に対しTHA+BSO+pOMT+臍切除を施行した。後療法は本人の希望で施行せず、術後3ヵ月に死亡の転帰となった。症例3は50歳女性。初診時の画像所見から卵巣癌疑い、子宮体癌疑い、腹膜播種疑い、臍腫瘍を指摘された。子宮内膜組織診や臍生検から癌の同定はできなかったが、臨床的に卵巣癌または子宮体癌と診断し、weekly Paclitaxel+Carboplatin 14サイクルを術前化学療法として施行した。TAH+BSO+pOMT+臍切除を施行し、卵巣癌IVB期(ypT3bN0M1、類内膜癌)の診断であった。同抗癌剤を継続後、Niraparibにて維持療法中であるが再発所見を認めない。3症例共に臍切除を施行したが、術後合併症は生じなかった。症状や画像所見から臍転移を疑う卵巣癌症例では積極的に切除し、病期が変わることで治療方針の決定や予後に影響を及ぼす可能性がある。(著者抄録)

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Hereditary gynecologic tumors and precision cancer medicine. International journal

Chikako Ogawa, Akira Hirasawa, Naoyuki Ida, Keiichiro Nakamura, Hisashi Masuyama

The journal of obstetrics and gynaecology research 48 ( 5 ) 1076 - 1090 2022.5

Language：English Publishing type：Research paper (scientific journal)

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.

DOI： 10.1111/jog.15197

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The Combination of D-dimer and Glasgow Prognostic Score Can Be Useful in Predicting VTE in Patients with Stage IIIC and IVA Ovarian Cancer.

Kotaro Kubo, Keiichiro Nakamura, Kazuhiro Okamoto, Hirofumi Matsuoka, Naoyuki Ida, Tomoko Haruma, Chikako Ogawa, Hisashi Masuyama

Acta medica Okayama 76 ( 2 ) 129 - 135 2022.4

Language：English Publishing type：Research paper (scientific journal)

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann-Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 μg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.

DOI： 10.18926/AMO/63406

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Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women. International journal

Mamiko Onuki, Kasumi Yamamoto, Hideaki Yahata, Hiroyuki Kanao, Harushige Yokota, Hisamori Kato, Kumi Shimamoto, Kazuhiro Takehara, Shoji Kamiura, Naotake Tsuda, Yuji Takei, Shogo Shigeta, Noriomi Matsumura, Hiroyuki Yoshida, Takeshi Motohara, Hidemichi Watari, Keiichiro Nakamura, Akihiko Ueda, Nobutaka Tasaka, Mitsuya Ishikawa, Yasuyuki Hirashima, Wataru Kudaka, Ayumi Taguchi, Takashi Iwata, Fumiaki Takahashi, Iwao Kukimoto, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Cancer science 113 ( 4 ) 1428 - 1434 2022.4

Language：English Publishing type：Research paper (scientific journal)

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

DOI： 10.1111/cas.15270

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肥満を伴う子宮体癌患者に対して腹腔鏡下手術を施行した2症例の検討

篠崎真里奈, 久保光太郎, 栗山千晶, 依田尚之, 岡本和浩, 松岡敬典, 小川千加子, 中村圭一郎, 増山寿

日本産科婦人科学会雑誌 74 ( 臨増 ) S - 475 2022.2

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Papers - NAKAMURA Keiichiro