Faculty Profiles - HATTORI Norifumi

Papers - HATTORI Norifumi

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肝門部胆管癌術後,三度の右側大腸癌を切除した一例

神原祐一, 上原圭, 小倉淳司, 村田悠記, 三品拓也, 鈴木優美, 國料俊男, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 佐藤雄介, 服部憲史, 中山吾郎, 相場利貞, 横山幸浩, 小寺泰弘, 江畑智希

日本消化器外科学会雑誌 Vol. 54 ( Suppl.2 ) page： 186 - 186 2021.11

腹腔鏡下仙骨合併腫瘍切除を施行した骨盤内巨大神経鞘腫の一例

西村元伸, 上原圭, 小倉淳司, 服部憲史, 中山吾郎, 國料俊男, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 横山幸浩, 小寺泰弘, 江畑智希

日本臨床外科学会雑誌 Vol. 82 ( 増刊 ) page： S932 - S932 2021.10

Blockade of CHRNB2 signaling with a therapeutic monoclonal antibody attenuates the aggressiveness of gastric cancer cells. Reviewed International journal

Mitsuro Kanda, Dai Shimizu, Shunsuke Nakamura, Koichi Sawaki, Shinichi Umeda, Takashi Miwa, Haruyoshi Tanaka, Yoshikuni Inokawa, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Goro Nakayama, Yohei Iguchi, Masahisa Katsuno, Yasuhiro Kodera

Oncogene Vol. 40 ( 36 ) page： 5495 - 5504 2021.9

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

Here, we evaluated the therapeutic potential of antibodies (Abs) targeting cholinergic receptor nicotinic beta 2 subunit (CHRNB2) in gastric cancer. To investigate the effects of these Abs on malignant phenotypes in vitro and in mouse xenograft models, we generated gene knockouts through genome editing, performed RNA interference-mediated knockdown of gene expression, and ectopically expressed CHRNB2 in gastric cancer cells. The effects of anti-CHRNB2 Abs on the proliferation of cancer cells were evaluated both in vitro and in vivo. We determined the effects of Chrnb2 deficiency on mice and the clinical significance of CHRNB2 expression in gastric cancer clinical specimens. Knockdown of CHRNB2 attenuated gastric cancer cell proliferation, whereas forced overexpression of CHRNB2 increased cell proliferation. Knockout of CHRNB2 significantly influenced cell survival and functions associated with metastasis. The effects of polyclonal Abs targeting the C- and N-termini of CHRNB2 guided the development of anti-CHRNB2 monoclonal Abs that inhibited the growth of gastric cancer cells in vitro and in vivo. Pathway analysis revealed that CHRNB2 interfered with signaling through the PI3K-AKT and JAK-STAT pathways. Chrnb2-deficient mice exhibited normal reproduction, organ functions, and motor functions. CHRNB2 regulates multiple oncological phenotypes associated with metastasis, and blockade of CHRNB2 expression using specific Abs shows promise for controlling metastasis in gastric cancer.

DOI： 10.1038/s41388-021-01945-9

Web of Science

PubMed

結腸癌腹膜播種に対する外科切除の意義

三品拓也, 上原圭, 小倉淳司, 村田悠記, 小池佳勇, 鈴木優美, 神原祐一, 西村元伸, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 佐藤雄介, 服部憲史, 中山吾郎, 横山幸浩, 小寺泰弘, 江畑智希

日本大腸肛門病学会雑誌 Vol. 74 ( 9 ) page： A209 - A209 2021.9

当科におけるBRAF V600E変異陽性大腸癌に対するBRAF阻害剤併用療法の使用経験

神野孝徳, 上原圭, 小倉淳司, 村田悠記, 三品拓也, 小池佳勇, 神原祐一, 鈴木優美, 西村元伸, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 服部憲史, 中山吾郎, 横山幸浩, 小寺泰弘, 江畑智希

日本大腸肛門病学会雑誌 Vol. 74 ( 9 ) page： A208 - A208 2021.9

当科における局所進行結腸癌に対する術前化学療法の臨床経験

小倉淳司, 上原圭, 小池佳勇, 村田悠記, 神野孝徳, 鈴木優美, 三品拓也, 神原祐一, 西村元伸, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 服部憲史, 中山吾郎, 横山幸浩, 小寺泰弘, 江畑智希

日本大腸肛門病学会雑誌 Vol. 74 ( 9 ) page： A200 - A200 2021.9

会陰部に広範に自壊した局所再発直腸粘液癌に対し、仙骨合併骨盤内臓全摘術+複数の筋皮弁再建を施行し、R0切除を達成し得た一例

神原祐一, 上原圭, 小倉淳司, 村田悠記, 三品拓也, 小池佳勇, 鈴木優美, 西村元伸, 伊神剛, 水野隆史, 山口淳平, 宮田一志, 尾上俊介, 渡辺伸元, 佐藤雄介, 服部憲史, 中山吾郎, 横山幸浩, 小寺泰弘, 江畑智希

日本大腸肛門病学会雑誌 Vol. 74 ( 9 ) page： A204 - A204 2021.9

A Possible Definition of Oligometastasis in Pancreatic Cancer and Associated Survival Outcomes. Reviewed International journal

Masaya Yamanaka, Masamichi Hayashi, Suguru Yamada, Fuminori Sonohara, Hideki Takami, Yoshikuni Inokawa, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

Anticancer research Vol. 41 ( 8 ) page： 3933 - 3940 2021.8

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

BACKGROUND: Oligometastatic cancer (OM) is possibly associated with relatively better survival outcomes. We attempted to identify cases in line with this OM concept. PATIENTS AND METHODS: A total of 130 cases with unresectable metastatic pancreatic cancer underwent non-curative surgery from April 2001 to December 2019. Sites of metastasis, clinicopathological information, and surgical outcomes were collected to formulate a better definition of OM. RESULTS: OM criteria were defined as having metastasis to a single organ, few countable lesions and low serum cancer antigen 19-9 level. The median overall survival after non-curative surgery of OM cases was 13.0 months and was significantly better than that of non-OM cases (8.4 months, p=0.003). CONCLUSION: We propose single-organ metastasis of limited tumor volume (H1 or P1/2 by the Japanese Society of Cancer of the Colon and Rectum classification) and low serum cancer antigen 19-9 level (<2,000 U/ml) as new criteria for defining OM pancreatic cancer.

DOI： 10.21873/anticanres.15189

Web of Science

PubMed

High Serum Uric Acid Levels Could Be a Risk Factor of Hepatocellular Carcinoma Recurrences. Reviewed International journal

Masamichi Hayashi, Suguru Yamada, Hiroshi Tanabe, Hideki Takami, Yoshikuni Inokawa, Fuminori Sonohara, Dai Shimizu, Norifumi Hattori, Mitsuro Kanda, Chie Tanaka, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera

Nutrition and cancer Vol. 73 ( 6 ) page： 996 - 1003 2021.7

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

BACKGROUND: The Apolipoprotein-related MORtality RISk (AMORIS) study in Sweden revealed that serum uric acid (SUA) was significantly associated with hepatobiliary cancer occurrence. However, the association with postoperative hepatocellular carcinoma (HCC) recurrence has not been reported. METHODS: A total of 256 surgically resected HCC patients were included (from January 2003 to December 2017) in this study. Comparisons in terms of clinicopathologic factors and long-term outcomes were made between patients with high SUA (>6.1 mg/dl) at the time of hepatectomy and low SUA. Besides, SUA data at one postoperative year (1POY) of the same cohort were collected and analyzed in the same manner. RESULTS: About 88.8% of tumor relapse sites were the remnant liver. High SUA levels were associated with male and well-differentiated HCCs. Recurrence-free survival (RFS) of high SUA patients was significantly inferior to low SUA patients [median survival time (MST): 22.7 vs. 28.5 mo, P = 0.033], whereas no difference was observed in overall survival (MST: both not reached, P = 0.771). RFS of high SUA patients at 1POY also showed significantly poorer outcomes than low SUA patients (MST: 29.3 vs. 57.0 mo, P = 0.049). CONCLUSIONS: High SUA implies a significant risk factor of activating hepatocarcinogenesis. Keeping the SUA level low may be recommended after HCC resections.

DOI： 10.1080/01635581.2020.1779758

Web of Science

PubMed

The carcinoembryonic antigen ratio is a potential predictor of survival in recurrent colorectal cancer. Reviewed

Yumi Suzuki, Atsushi Ogura, Kay Uehara, Toshisada Aiba, Noriaki Ohara, Yuki Murata, Takanori Jinno, Takuya Mishina, Yusuke Sato, Norifumi Hattori, Goro Nakayama, Yasuhiro Kodera, Tomoki Ebata

International journal of clinical oncology Vol. 26 ( 7 ) page： 1264 - 1271 2021.7

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

BACKGROUND: The carcinoembryonic antigen (CEA) "value" itself is often useless in patients with a normal CEA level at initial presentation and those with tumor-irrelevant elevated CEA. Although the unified marker using CEA has been desirable for recurrent tumor staging as well as for primary tumor staging, little is known concerning its relationship with the survival of patients with recurrent colorectal cancer in particular. METHODS: This retrospective historical study included patients who experienced disease relapse after curative surgery for stage I-III colorectal cancer between 2006 and 2018. A total of 129 patients with recurrent disease after curative surgery for colorectal cancer were included. We focused on the CEA "ratio" (CEA-R: the ratio of the CEA level at the time of recurrence to that measured 3 months before recurrence) and aimed to evaluate the correlation between CEA-R and survival in recurrent colorectal cancer. RESULTS: Patients with a high CEA-R (≥ 2) exhibited significantly worse 2 year survival than those with a low CEA-R (< 2) (88.1% vs. 44.9%, P < 0.001), irrespective of the CEA value before primary resection. Multivariate analyses demonstrated that the CEA-R (HR; 3.270, 95% CI 1.646-6.497, P = 0.001) was a significant prognostic factor. CONCLUSION: The CEA-R is a potential marker stratifying the survival of patients with disease relapse who exhibit aggressive biology at recurrent disease foci. As a novel marker, the CEA-R would serve as a clinical guide for tailoring treatment strategies at the time of disease relapse in patients with colorectal cancer.

DOI： 10.1007/s10147-021-01919-7

Web of Science

PubMed

高齢者胃癌に対する治療の工夫高齢者胃癌手術症例に対する高齢者機能の転帰と工夫

田中千恵, 中西香企, 清水大, 服部憲史, 神田光郎, 中山吾郎, 小池聖彦, 小寺泰弘

日本消化器外科学会総会 Vol. 76回 page： WS10 - 9 2021.7

高齢者胃癌に対する治療の工夫高齢者胃癌手術症例に対する高齢者機能の転帰と工夫

田中千恵, 中西香企, 清水大, 服部憲史, 神田光郎, 中山吾郎, 小池聖彦, 小寺泰弘

日本消化器外科学会総会 Vol. 76回 page： WS10 - 9 2021.7

Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer. Reviewed International journal

Atsushi Ogura, Kay Uehara, Toshisada Aiba, Masanori Sando, Aya Tanaka, Noriaki Ohara, Yuki Murata, Yusuke Sato, Norifumi Hattori, Goro Nakayama, Tomoki Ebata, Yasuhiro Kodera, Masato Nagino

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology Vol. 47 ( 5 ) page： 1005 - 1011 2021.5

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

INTRODUCTION: The oncological benefit of neoadjuvant chemotherapy (NAC) alone for locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to clarify the clinical risk factors for poor prognosis before and after NAC for decision making regarding additional treatment in patients with LARC. MATERIALS AND METHODS: We examined a total of 96 patients with MRI-defined poor-risk locally advanced mid-low rectal cancer treated by NAC alone between 2006 and 2018. Survival outcomes and clinical risk factors for poor prognosis before and after NAC were analyzed. RESULTS: In the median follow-up duration after surgery of 60 months (3-120), the rates of 5-year overall survival (OS), relapse-free survival (RFS), and local recurrence (LR) were 83.6%, 78.4%, and 8.2%, respectively. In the multivariate analyses, patients with cT4 disease had a significantly higher risk of poor OS (HR; 6.10, 95% CI; 1.32-28.15, P = 0.021) than those with cT3 disease. After NAC, ycN+ was significantly associated with a higher risk of poor OS (HR; 5.92, 95% CI; 1.27-27.62, P = 0.024) and RFS (HR; 2.55, 95% CI; 1.01-6.48, P = 0.048) than ycN-. In addition, patients with CEA after NAC (post-CEA) ≥ 5 ng/ml had a significantly higher risk LR (HR; 5.63, 95% CI; 1.06-29.93, P = 0.043). CONCLUSION: NAC alone had an insufficient survival effect on patients with cT4 disease, ycN+, or an elevated post-CEA level. In contrast, NAC alone is a potential treatment for other patients with LARC.

DOI： 10.1016/j.ejso.2020.10.038

Web of Science

PubMed

当院におけるアフリベルセプトの使用経験について

大原規彰, 上原圭介, 相場利貞, 小倉淳司, 山東雅紀, 田中綾, 村田悠記, 江畑智希, 横山幸浩, 伊神剛, 深谷昌秀, 水野隆史, 山口淳平, 中山吾郎, 服部憲史, 佐藤雄介, 小寺泰弘, 梛野正人

日本大腸肛門病学会雑誌 Vol. 74 ( 5 ) page： 342 - 342 2021.5

下部進行直腸癌に対する術前化学療法の効果と限界

小倉淳司, 上原圭介, 相場利貞, 山東雅紀, 田中綾, 大原規彰, 村田悠記, 江畑智希, 横山幸浩, 伊神剛, 深谷昌秀, 水野隆史, 山口淳平, 中山吾郎, 服部憲史, 佐藤雄介, 小寺泰弘, 梛野正人

日本大腸肛門病学会雑誌 Vol. 74 ( 5 ) page： 337 - 337 2021.5

Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53-Bcl-2 intrinsic apoptosis pathway. Reviewed International journal

Takashi Miwa, Mitsuro Kanda, Dai Shimizu, Shinichi Umeda, Koichi Sawaki, Haruyoshi Tanaka, Chie Tanaka, Norifumi Hattori, Masamichi Hayashi, Suguru Yamada, Goro Nakayama, Masahiko Koike, Yasuhiro Kodera

British journal of cancer Vol. 124 ( 8 ) page： 1449 - 1460 2021.4

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

BACKGROUND: Gastric cancer (GC) with hepatic metastasis has a poor prognosis. Understanding the molecular mechanisms involved in hepatic metastasis may contribute to the development of sensitive diagnostic biomarkers and novel therapeutic strategies. METHODS: We performed transcriptome analysis of surgically resected specimens from patients with advanced GC. One of the genes identified as specifically associated with hepatic metastasis was selected for detailed analysis. GC cell lines with knockout of the candidate gene were evaluated in vitro and in vivo. Expression of the candidate gene was analysed in GC tissues from 300 patients. RESULTS: Ethanolamine kinase 2 (ETNK2) was differentially upregulated in GC patients with hepatic metastasis. ETNK2 expression was elevated in GC cell lines derived from haematogenous metastases. ETNK2 knockout significantly suppressed proliferation, invasion, and migration; increased apoptosis; reduced Bcl-2 protein expression; and increased phosphorylated p53 expression. In mouse xenograft models, ETNK2 knockout virtually abolished hepatic metastasis. Stratification of GC patients based on ETNK2 mRNA level revealed significant associations between high ETNK2 tumour expression and both hepatic recurrence and worse prognosis. CONCLUSIONS: Upregulation of ETNK2 in GC enhances hepatic metastasis, possibly via dysregulation of p53-Bcl-2-associated apoptosis. ETNK2 expression may serve as a biomarker for predicting hepatic recurrence and a therapeutic target.

DOI： 10.1038/s41416-021-01271-7

Web of Science

PubMed

GAD1の食道扁平上皮癌根治的切除後予後予測バイオマーカーとしての意義

岸田貴喜, 神田光郎, 清水大, 田中千恵, 園原史訓, 猪川祥邦, 高見秀樹, 服部憲史, 林真路, 山田豪, 中山吾郎, 小池聖彦, 藤原道隆, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 121回 page： PS - 4 2021.4

転移性肝腫瘍に対する至適治療戦略術前化学療法の可否につき考える

林真路, 山田豪, 高見秀樹, 猪川祥邦, 園原史訓, 田中伸孟, 栗本景介, 砂川祐輝, 加藤吉康, 中川暢彦, 鈴木雄之典, 山中雅也, 清水大, 服部憲史, 神田光郎, 田中千恵, 中山吾郎, 小池聖彦, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 121回 page： SF - 5 2021.4

膵癌における術前治療中の腫瘍マーカーの比較・検討

砂川祐輝, 山田豪, 田中伸孟, 園原史訓, 猪川祥邦, 高見秀樹, 林真路, 服部憲史, 神田光郎, 田中千恵, 中山吾郎, 小池聖彦, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 121回 page： PS - 4 2021.4

膵癌におけるオリゴメタスタシスの臨床的意義

山中雅也, 山田豪, 林真路, 園原史訓, 猪川祥邦, 高見秀樹, 服部憲史, 神田光郎, 田中千恵, 中山吾郎, 小池聖彦, 藤原道隆, 小寺泰弘

日本外科学会定期学術集会抄録集 Vol. 121回 page： SF - 5 2021.4

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Papers - HATTORI Norifumi