研究者詳細 - 齋藤　豪

論文 - 齋藤　豪

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Large number of CD68+/CD163+ Hofbauer cells and characteristic vascular structural alterations in the placental villi of cases with placenta accreta spectrum.

Hazuki Kashiwagi, Kengo Shigehara, Terufumi Kubo, Yoshihiko Hirohashi, Tasuku Mariya, Kazuhiko Matsuo, Tomoyuki Minowa, Shin-Ichi Ishioka, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Toshihiko Torigoe

Medical molecular morphology 2025年03月 [国内誌]

Placenta accreta spectrum (PAS) is a serious disease leading to complications and maternal death. The objective of the study was to characterize the placental villi and blood vessels of PAS villi histopathologically. We investigated 10 cases of PAS (five cases of placenta increta, two cases of placenta accreta, and three cases of placenta percreta) histologically. Immunohistochemical staining using anti-CD68 or anti-CD163 antibodies was performed to detect and count Hofbauer cells. Immunohistochemical staining with an anti-CD34 antibody was used to detect vascular endothelial cells, and the number and area of vessels were analyzed. The numbers of CD68-positive or CD163-positive Hofbauer cells were larger in PAS cases compared with control cases. The vascular area in villi was smaller in PAS cases compared with control cases. The number of blood vessels in villi was slightly higher in PAS cases than in control cases. The numbers of Hofbauer cells and vessels in villi were larger in PAS cases compared with control cases, whereas the area of vessels in villi was smaller in PAS cases compared with control cases. Although their biological meaning is elusive, these findings provide novel insights into the pathogenesis of PAS, particularly regarding the role of Hofbauer cells in immune-suppressive role and angiogenesis and the alterations in vascular structure and hemodynamics in the chorionic villi.

DOI PubMed

Maternal age and the rising incidence of hypertensive disorders of pregnancy: A comprehensive analysis of national claims data from Japan.

Naomi Maeda, Masayuki Koyama, Shintaro Takatsuka, Keisuke Oyatani, Nobuaki Himuro, Tasuku Mariya, Yoshika Kuno, Shiro Hinotsu, Tsuyoshi Saito, Hirofumi Ohnishi

PloS one 20 ( 2 ) e0319177 2025年 [国際誌]

BACKGROUND: Hypertensive disorders of pregnancy (HDP) significantly increase the risk of developing hypertension and cardiovascular disease (CVD) later in life and are a major cause of maternal mortality. However, little is known about the nationwide, long-term, all-inclusive status of HDP. OBJECTIVE: To estimate the incidence of HDP from 2011 to 2019 in Hokkaido, Japan, with a focus on age groups. METHODS: Using National Database (NDB) insurance medical data, a retrospective analysis was conducted. Due to the absence of direct pregnancy data, birth numbers were used as a surrogate for the number of pregnant women to calculate the incidence of HDP. RESULTS: The average incidence rate of HDP over 9 years was 6.37%. The incidence rate was lowest among women aged 25-29 years, at 5.58% (95% confidence interval [CI]: 5.43-5.73), and increased with age, peaking at 10.58% (95% CI: 10.10-11.09) among women over 40 years. Notably, the incidence rate for women under 20 years of age was 6.70% (95% CI: 5.97-7.51), which was higher than that for women in their 20s. A mean annual increase of 0.25% in age-adjusted incidence was observed during this period, which was statistically significant (R² = 0.87, p < 0.01). CONCLUSION: This study reveals that the risk of developing HDP is associated with both older childbearing and younger pregnancies and follows a J-curve, suggesting that factors other than maternal aging also contribute to the increased incidence of HDP and that further research on risk factors for HDP, which is on the rise worldwide, is urgently needed.

DOI PubMed

Identification and phenotypic characterization of neoantigen-specific cytotoxic CD4+ T cells in endometrial cancer

Minami Fusagawa, Serina Tokita, Kenji Murata, Tasuku Mariya, Mina Umemoto, Shintaro Sugita, Kazuhiko Matsuo, Yoshihiko Hirohashi, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Cancer Immunology Research ( American Association for Cancer Research (AACR) ) 2024年12月

Abstract Tumor-reactive CD4+ T cells often accumulate in the tumor microenvironment (TME) in human cancer, but their functions and roles in antitumor responses remain elusive. Here, we investigated the immunopeptidome of HLA class II–positive (HLA-II+) endometrial cancer with an inflamed TME using a proteogenomic approach. We identified HLA-II neoantigens, one of which induced polyclonal CD4+ tumor-infiltrating lymphocyte (TIL) responses. We then experimentally demonstrated that neoantigen-specific CD4+ TILs lyse target cells in an HLA-II–dependent manner. Single cell transcriptomic analysis of the TME coupled with T-cell receptor (TCR) sequencing revealed the presence of CD4+ T-cell clusters characterized by CXCL13 expression. The CXCL13+ clusters contained two subclusters with distinct cytotoxic gene expression patterns. The identified neoantigen-specific CD4+ T cells were found exclusively in one of the CXCL13+ subclusters characterized by granzyme B and CCL5 expression. These results demonstrate the involvement of tumor-reactive CD4+ T cells with cytotoxic function in immune surveillance of endometrial cancer and reveal their transcriptomic signature.

DOI

【エネルギーデバイスアラカルト-知っておきたい使い方の留意点と技術革新】総論モードの特性と使い分け

玉手雅人, 松浦基樹, 齋藤豪

臨床婦人科産科 ( (株)医学書院 ) 78 ( 12 ) 1083 - 1090 2024年12月

＜文献概要＞●電気メスのモードと本体の使い分け:電気メスの効果と性能は,モードと出力設定で変化するが,電気メスを接続する本体の種類によっても異なる.●他の手術機器との使い分け,バイポーラ・アドバンスドバイポーラ・バイクランプの使い分け:電気メス,バイポーラ,アドバンスドバイポーラ,超音波凝固切開装置の組み合わせは術式・手技・コストで考慮する.●機械の特性を理解して,術者が自身の技量や手術スタイルに合わせてエネルギーデバイスを扱うことが重要と思われる.

【エネルギーデバイスアラカルト-知っておきたい使い方の留意点と技術革新】各種デバイスの原理・有用性と使用上の注意点シーリングデバイス

松浦基樹, 玉手雅人, 齋藤豪

臨床婦人科産科 ( (株)医学書院 ) 78 ( 12 ) 1104 - 1111 2024年12月

＜文献概要＞●シーリングデバイスは直径7mmまでの血管や組織束がシール可能であり,超音波凝固切開装置より太い血管をシールすることができる.●シーリングデバイスは高周波エネルギーを瞬時に供給して血管のシールを行うため,手術効率が向上するだけではなく,熱の拡散を極力抑えることで周囲の組織への影響を最小限に抑えることができる.●外科医は各デバイスの原理や有用性・注意点などを習熟したうえで,これらのデバイスを使用するべきである.

Impact of colposcopy-guided carbon dioxide laser vaporization therapy on peripheral cervical intraepithelial neoplasia lesions.

Tasuku Mariya, Akira Nishikawa, Mina Umemoto, Shiori Ogawa, Tsuyoshi Saito

Taiwanese journal of obstetrics & gynecology 63 ( 6 ) 846 - 852 2024年11月 [国際誌]

OBJECTIVE: Laser vaporization is less invasive than conization for cervical intraepithelial neoplasia (CIN). The outcome of laser vaporization for CIN is empirically known to depend on the colposcopic findings, especially localization of the lesion. In this study, we sought to identify factors involved in the outcome of laser vaporization. MATERIALS AND METHODS: We retrospectively investigated 290 cases of CIN (CIN2, n = 180; CIN3, n = 110) treated with laser evaporation at Nishikawa Women's Health Clinic between 2018 and 2021. All treatments were performed using a carbon dioxide laser under either colposcopic vision (n = 172) or direct vision using a vaginal speculum (n = 118). Risk factors were statistically examined for cure rate after treatment. RESULTS: Multivariate analysis using a logistic regression model identified independent factors affecting the success of treatment to be high-risk human papillomavirus infection status preoperatively, CIN grade, presence of CIN lesions at the periphery of the cervix, and the surgical method used. Colposcopy-guided laser vaporization reduced the risk of treatment failure by 84% (odds ratio 0.16, 95% confidence interval 0.06-0.46; p = 0.001) compared with direct vision using a vaginal speculum. For lesions at the periphery of the cervix, most of the treatment failures were in the group that was not guided by colposcopy (p = 0.031). CONCLUSION: The presence of a peripheral CIN lesion was suggested to be a risk factor for treatment failure. Laser vaporization under colposcopic vision is recommended for treatment of peripheral CIN lesions.

DOI PubMed

Human papillomavirus self-sampling and urine-sampling tests and the management and short-term outcomes of cervical intraepithelial neoplasia: A prospective observational study.

Motoki Matsuura, Masato Tamate, Sachiko Nagao, Taishi Akimoto, Fukiko Kasuga, Kimihito Saito, Satoshi Shikanai, Yoko Nishimura, Mizue Teramoto, Tsuyoshi Saito

The journal of obstetrics and gynaecology research 50 ( 10 ) 1801 - 1807 2024年10月 [国際誌]

AIM: The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests. METHODS: This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests. RESULTS: There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method. CONCLUSIONS: Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

DOI PubMed

Successful Outcome of Stage IB3 Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy: A Case Report.

Masato Tamate, Motoki Matsuura, Masayuki Someya, Tasuku Mariya, Shinichi Ishioka, Tsuyoshi Saito

Cureus 16 ( 10 ) e71626 2024年10月 [国際誌]

Vaginal trachelectomy, which involves resecting the cervix and its parametrium, is a fertility-sparing option for the treatment of early-stage cervical cancer. Although no consensus has been reached on whether simple or radical trachelectomy is preferable, the vaginal approach is typically avoided for tumors larger than 2 cm due to concerns about recurrence. However, some evidence suggests that fertility preservation may still be viable for select patients with larger tumors. This case report describes a woman with bulky cervical cancer who wished to preserve her fertility. After undergoing neoadjuvant chemotherapy (NAC) and vaginal radical trachelectomy (VRT), she achieved a favorable oncological and perinatal outcome, successfully giving birth to a near-full-term baby. The report outlines the patient's management before, during, and after the procedure, including perinatal care. While careful selection of candidates is crucial, accumulating case reports and future trials are expected to shed more light on this treatment approach.

DOI PubMed

Risk-reducing salpingo-oophorectomy for hereditary breast and ovarian cancer patients with vaginal natural orifice transluminal endoscopic surgery (vNOTES).

Masato Tamate, Motoki Matsuura, Sachiko Nagao, Shoko Kurokawa, Taishi Akimoto, Tsuyoshi Saito

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2024年09月 [国際誌]

DOI PubMed

Identification of immunogenic HLA class I and II neoantigens using surrogate immunopeptidomes.

Serina Tokita, Minami Fusagawa, Satoru Matsumoto, Tasuku Mariya, Mina Umemoto, Yoshihiko Hirohashi, Fumitake Hata, Tsuyoshi Saito, Takayuki Kanaseki, Toshihiko Torigoe

Science advances 10 ( 38 ) eado6491 2024年09月 [国際誌]

Neoantigens arising from somatic mutations are tumor specific and induce antitumor host T cell responses. However, their sequences are individual specific and need to be identified for each patient for therapeutic applications. Here, we present a proteogenomic approach for neoantigen identification, named Neoantigen Selection using a Surrogate Immunopeptidome (NESSIE). This approach uses an autologous wild-type immunopeptidome as a surrogate for the tumor immunopeptidome and allows human leukocyte antigen (HLA)-agnostic identification of both HLA class I (HLA-I) and HLA class II (HLA-II) neoantigens. We demonstrate the direct identification of highly immunogenic HLA-I and HLA-II neoantigens using NESSIE in patients with colorectal cancer and endometrial cancer. Fresh or frozen tumor samples are not required for analysis, making it applicable to many patients in clinical settings. We also demonstrate tumor prevention by vaccination with selected neoantigens in a preclinical mouse model. This approach may benefit personalized T cell-mediated immunotherapies.

DOI PubMed

Microbiological investigation of pregnancies following vaginal radical trachelectomy using 16S rRNA sequencing of FFPE placental specimens.

Risa Tsunematsu, Tasuku Mariya, Mina Umemoto, Shiori Ogawa, Wataru Arai, Suguru E Tanaka, Kyota Ashikawa, Terufumi Kubo, Yoshiyuki Sakuraba, Tsuyoshi Baba, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Saito

FEBS open bio 2024年09月 [国際誌]

This study examined the risk of intrauterine infection associated with radical trachelectomy (RT) in early-stage cervical cancer patients. This procedure preserves fertility but is linked to increased risk of intrauterine infection due to cervical defects during pregnancy. DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) placental specimens of 23 pregnant post-RT patients and 16S rRNA gene sequencing was used for bacterial identification. The prevalence of Lactobacillus crispatus and Burkholderia stabilis was significantly higher in the non-chorioamnionitis group. In contrast, alpha diversity analysis using the PD index showed significantly higher diversity in the chorioamnionitis group (P = 0.04). The demonstrated relationship between chorioamnionitis and microbial diversity affirms the importance of controlling the genital bacterial flora in pregnancies following RT.

DOI PubMed

Step-by-step demonstration of "sciatic-nerve-preserved beyond-LEER" in a Thiel-embalmed cadaver: a novel salvage surgery for recurrent gynecologic malignancies.

Hiroyuki Kanao, Masato Tamate, Motoki Matsuura, Sachiko Nagao, Miseon Nakazawa, Shutaro Habata, Tsuyoshi Saito

Journal of gynecologic oncology 35 ( 5 ) e112 2024年09月 [国際誌]

OBJECTIVE: Complete resection is the curative treatment choice for recurrent gynecological malignancies. Laterally extended endopelvic resection (LEER) is an effective surgical salvage therapy for lateral recurrence. However, when a recurrent tumor occupies the ischial spine and sacrum, LEER is not indicated, and surgical salvage therapy is abandoned. Theoretically, complete resection of such a tumor is possible by additional pelvic bone resection along with the standard LEER. Nevertheless, owing to the anatomical complexities of the beyond-LEER procedure, 2 major issues should be solved: sciatic nerve injury and tumor disruption during pelvic bone amputation. To overcome these technical challenges, we applied a multidirectional beyond-LEER approach, a novel salvage surgical procedure, with an aim of demonstrating its technical feasibility. METHODS: We created a simulation model of a laterally recurrent tumor that occupied the right ischial spine and sacrum in a Thiel-embalmed cadaver. RESULTS: Multidirectional approaches, including laparoscopic, perineal, and dorsal phases, were safely applied. We laparoscopically marked the L4-L5-S1 complex and S2 nerve with different colored tapes, and by pulling them out into a dorsal surgical field, the sciatic nerve was safely preserved. The dissection lines of the multidirectional approaches were aligned using tapes as landmarks, and complete tumor clearance without tumor disruption was accomplished. By following the cadaveric training, the first laparoscopic-assisted beyond-LEER procedure was successfully performed in a patient with recurrent ovarian cancer. CONCLUSION: Using a Thiel-embalmed cadaver, we demonstrated the technical feasibility of a sciatic nerve-preserved beyond-LEER procedure, which was successfully performed in a patient with recurrent ovarian cancer.

DOI PubMed

IB3期の子宮頸癌に対して術前化学療法後に広汎子宮頸部摘出術を施行し分娩となった1例

佐藤冴子, 染谷真行, 玉手雅人, 松浦基樹, 森下美幸, 馬場剛, 石岡伸一, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 71回 48 - 48 2024年09月

ロボット支援子宮全摘出術での発光式尿管カテーテルと子宮トランスイルミネーターの使用経験

幅田周太朗, 黒川晶子, 有元千紘, 長尾沙智子, 玉手雅人, 秋元太志, 松浦基樹, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 71回 78 - 78 2024年09月

【産婦人科領域における情報リテラシー-ビッグデータとバイオインフォマティクスの活用】婦人科腫瘍領域におけるAIの活用

梅本美菜, 真里谷奨, 南部優太, 藤野雄一, 鳥越俊彦, 齋藤豪

産婦人科の実際 ( 金原出版(株) ) 73 ( 8 ) 829 - 833 2024年08月

＜文献概要＞AI(人工知能),なかでも深層学習(deep learning)を用いた技術は,医療においても数多くの分野で応用が試みられている。産婦人科領域においてもそれは決して例外ではない。扱う対象データを画像,病理画像や放射線画像,ならびに内視鏡画像に絞ったとしても,多種多様な検討が行われてきた。本稿では,AI全体の潮流についても触れつつ,婦人科腫瘍領域のなかでも特に深層学習を用いた病理診断,細胞診および組織診にまつわるAIの活用について述べる。

【産婦人科領域における情報リテラシー-ビッグデータとバイオインフォマティクスの活用】婦人科腫瘍領域におけるAIの活用

梅本美菜, 真里谷奨, 南部優太, 藤野雄一, 鳥越俊彦, 齋藤豪

産婦人科の実際 ( 金原出版(株) ) 73 ( 8 ) 829 - 833 2024年08月

当院における類内膜癌G3症例の細胞診・病理形態学的評価と臨床経過の検討

幅田周太朗, 齋藤晋平, 有元千紘, 野藤五沙, 長尾沙智子, 黒川晶子, 玉手雅人, 真里谷奨, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 66回 327 - 327 2024年07月

婦人科HBOC専門外来の設置・運用によるクライエントの意思決定支援への効果の検証

古来愛香, 真里谷奨, 田中佑弥, 小松茅乃, 宮崎幸子, 石川亜貴, 齋藤豪, 櫻井晃洋

日本遺伝カウンセリング学会誌 ( (一社)日本遺伝カウンセリング学会 ) 45 ( 2 ) 120 - 120 2024年07月

Analysis of Treatment Response With Proteins Related to Tumor Immunity in Postoperative Irradiated Cervical Cancer Patients.

Shoh Mafune, Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Ryu Okuda, Masahiro Iwasaki, Motoki Matsuura, Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-Ichi Sakata

Anticancer research 44 ( 7 ) 3077 - 3086 2024年07月 [国際誌]

BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

DOI PubMed

当院における類内膜癌G3症例の細胞診・病理形態学的評価と臨床経過の検討

幅田周太朗, 齋藤晋平, 有元千紘, 野藤五沙, 長尾沙智子, 黒川晶子, 玉手雅人, 真里谷奨, 秋元太志, 松浦基樹, 岩崎雅宏, 齋藤豪

日本婦人科腫瘍学会学術講演会プログラム・抄録集 ( (公社)日本婦人科腫瘍学会 ) 66回 327 - 327 2024年07月

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