Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   消化器内科学講座   講師  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

  Yuto Numata, Noriyuki Akutsu, Masashi Idogawa, Kohei Wagatsuma, Yasunao Numata, Keisuike Ishigami, Tomoya Nakamura, Takehiro Hirano, Yujiro Kawakami, Yoshiharu Masaki, Ayako Murota, Shigeru Sasaki, Hiroshi Nakase

  Hepatology research : the official journal of the Japan Society of Hepatology    2024.03  [International journal]

  　View Summary

  A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

  DOI PubMed

• Generalized crystal-storing histiocytosis with noncirrhotic portal hypertension: an autopsy case report.

  Yasunao Numata, Shigeru Sasaki, Kazufumi Magara, Akira Takasawa, Taro Sugawara, Naruki Ohara, Noriyuki Akutsu, Tadashi Hasegawa, Makoto Osanai, Hiroshi Nakase

  Clinical journal of gastroenterology   16 ( 3 ) 450 - 456  2023.04  [Domestic journal]

  　View Summary

  Crystal-storing histiocytosis (CSH) is a rare disease associated with the accumulation of histiocytes containing crystalline matter within their cytoplasm. Herein, we present the case of a female patient who was diagnosed with Tolosa-Hunt syndrome at 45 years of age and idiopathic retroperitoneal fibrosis when she was 48 years. She developed portal hypertension (PH), but did not present with cirrhosis; as such, the cause of PH was not identified. Her PH gradually worsened when she was 54 years, and at the age of 60 years, she died from an acute subdural hematoma. Autopsy revealed retroperitoneal fibrosis with severe fibrosis extending around the hepatic veins and into the porta hepatis. Histologically, the retroperitoneal tissue showed a dense infiltrate of eosinophilic histiocytes with crystal structures in the cytoplasm, which was pathologically diagnosed as CSH. Nodular regenerative hyperplasia was observed in the liver parenchyma, whereas cirrhosis was not. In the present case, CSH caused fibrosis, which was believed to be the cause of PH. In addition, we considered that nodular regenerative hyperplasia caused by the altered hepatic blood flow due to treatment of gastric varices contributed to worsening PH. Hence, CSH should be considered as an underlying disease in noncirrhotic portal hypertension.

  DOI PubMed

• Serum soluble Fas levels and incidence of liver cancer in nested case-control study.

  Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Toshiyuki Kubo, Noriyuki Akutsu, Yasushi Sasaki, Hiroshi Nakase, Yingsong Lin, Youichi Kurozawa, Kenji Wakai, Akiko Tamakoshi

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology    2022.12  [International journal]

  　View Summary

  BACKGROUND: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case-control study nested in the JACC Study. METHODS: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects. Patients diagnosed with liver cancer were regarded as cases. Two or three controls were selected and matched for sex, age, and geographical area. Conditional logistic regression was used to estimate odds ratios (ORs) for cancer incidence associated with sFas. RESULTS: This study contained 86 cases and 249 controls. After controlling for alcohol intake, body mass index, smoking, and hepatitis viral infection, participants with high sFas showed elevated risk of cancer (P-trend = 0.003) and the third tertile of sFas showed a higher risk compared to the first tertile (OR = 3.53, 95% confidence interval (CI) = 1.28-9.69). In hepatocellular carcinoma, high sFas was associated with elevated risk (P-trend < 0.001). In men and the elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for 3 years, high sFas was related to liver cancer risk (P-trend = 0.033) and the third tertile showed a higher risk compared to the first (OR = 2.94, 95%CI = 0.94-9.14). CONCLUSIONS: High serum sFas may be related to future risk of liver cancer. IMPACT: Our findings highlight this biomarker for further analysis in pooled investigations with different/larger prospective cohorts.

  DOI PubMed

• A case of hepatocellular carcinoma with long-term survival by multidisciplinary treatment for cranial and skeletal muscle metastases.

  Noriyuki Akutsu, Yujiro Kawakami, Yasunao Numata, Takehiro Hirano, Kohei Wagatsuma, Keisuke Ishigami, Shigeru Sasaki, Hiroshi Nakase

  Clinical journal of gastroenterology   15 ( 5 ) 960 - 967  2022.10  [Domestic journal]

  　View Summary

  We report a case in which multidisciplinary treatment was effective for hepatocellular carcinoma (HCC) with cranial and skeletal muscle metastases. A 55-year-old male with HCC received sorafenib for lung metastases. He was admitted to our hospital due to the skull metastasis detected by fluorodeoxyglucose positron emission tomography (FDG-PET). The patient underwent resection for skull metastasis. After the surgical treatment, he was treated with sorafenib again. Eight months after craniectomy, FDG-PET showed FDG uptake in the semimembranosus and semitendinosus muscles. Histopathological examination of the muscle biopsy revealed HCC muscle metastasis. Sorafenib treatment was discontinued. The investigational new drug (tegafur-gimeracil-oteracil) and tegafur-uracil were used for the treatment. These treatments proved to be ineffective as the lung metastases enlarged and new metastases appeared on the mediastinal lymph nodes and dura cava. The patient was unable to walk due to the enlarged thigh muscle metastases. Sorafenib was re-administered, which reduced the enlargement of the lung and mediastinal lymph nodes. Dural metastases were treated with resection and radiotherapy. Additional radiation therapy to the thigh muscles relieved the patient from pain experienced during walking. Sorafenib treatment was continued for the next 3 years. The patient survived for 4 years after the skull resection.

  DOI PubMed

• Genomic analysis of an aggressive case with metastatic intrahepatic mucinous cholangiocarcinoma.

  Yoshiharu Masaki, Noriyuki Akutsu, Yasushi Adachi, Keisuike Ishigami, Norikazu Iwata, Takao Endo, Yoshifumi Ishii, Yasushi Sasaki, Minoru Nagayama, Yasutoshi Kimura, Hiroshi Nakase

  Clinical journal of gastroenterology   15 ( 4 ) 809 - 817  2022.08  [Domestic journal]

  　View Summary

  Intrahepatic mucinous cholangiocarcinoma (IHMC) is rare and behaves notoriously; however, the details of the clinicopathological characteristics of IHMC remain unknown. A 70-year-old man was admitted for examination of the hepatic mass in the S1 segment. He underwent extended left hepatic lobectomy. Histopathological evaluation demonstrated mixed papillary carcinoma that comprised well to moderately differentiated tubular adenocarcinoma and signet-ring cell carcinoma with large amounts of mucus lakes. Tumor was relapsed 9 months after surgery. Although he received chemotherapy with the combination of gemcitabine and cisplatin, he had renal failure and discontinued the chemotherapy. He received palliative radiotherapy for metastasis in the cervical spine. Then, the patient treated with S-1, however, he died 16 months after the initial diagnosis. The autopsy findings showed multiple nodules in the lungs, pleura, kidneys, adrenal glands, stomach, pancreas, and lymph nodes. Histological examination revealed that all nodules were IHMC. Next-generation sequencing revealed that somatic mutations in ADGRB3, TAF1L and EPHA3 may affect carcinogenesis, and those in TAF1, EPHA3, PIK3C2B, FN1, ERBB3, BRIP1, SYNE1 and TGFBR2 may affect metastasis. Molecular carcinogenesis of IHMC may be distinct from that of ordinary cholangiocarcinoma. Further studies are needed to elucidate the genetic mutations and their functions in IHMC.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 高齢者切除不能膵癌患者に対するGEM+nabPTX療法の有効性と安全性

  大和田 紗恵, 室田 文子, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

  日本高齢消化器病学会誌 ( (NPO)日本高齢消化器病学会 )  24 ( 2 ) 81 - 88  2022.02

  　View Summary

  GEM+nabPTX(GnP)を施行した切除不能膵癌をO群(≧75歳)28例とY群(<75歳)52例の2群に分け、有効性・安全性を比較検討した。無増悪生存期間はO群8.9ヵ月、Y群7.8ヵ月(P=0.59)、生存期間はO群17.2ヵ月、Y群22.1ヵ月(P=0.22)であり、多変量解析の結果、年齢はいずれにおいても独立した予後因子とはならなかった。4ヵ月目までのRelative dose intensityはO群で有意に低かった(O群64%、Y群84%、P=0.025)。有害事象の頻度は両群で同等であったが、O群の有害事象中止症例は全例二次治療に移行できなかった。高齢者でもGnPを実施可能だが、より緻密な忍容性評価を要する。(著者抄録)

• 後腹膜線維症に対するEUS-FNAの可能性

  川上 裕次郎, 本谷 雅代, 高田 夢実, 平野 雄大, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

  Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 )  63 ( Suppl.2 ) 2047 - 2047  2021.10

• 当科における胆道癌に対する化学放射線療法の治療成績

  平野 雄大, 本谷 雅代, 我妻 康平, 沼田 泰尚, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 佐々木 茂, 仲瀬 裕志

  日本消化器病学会雑誌 ( (一財)日本消化器病学会 )  118 ( 臨増大会 ) A468 - A468  2021.10

• ステロイド治療によって機能性消化管障害が改善したIgG4関連疾患の1例

  平野 雄大, 川上 裕次郎, 我妻 康平, 沼田 泰尚, 石上 敬介, 柾木 喜晴, 室田 文子, 本谷 雅代, 阿久津 典之, 佐々木 茂, 神田 真聡, 仲瀬 裕志

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  129回・123回   33 - 33  2021.09

• 当科における肝細胞癌に対するラムシルマブの使用経験

  沼田 泰尚, 沼田 有斗, 谷口 正浩, 我妻 康平, 川上 裕次郎, 石上 敬介, 柾木 喜晴, 室田 文子, 阿久津 典之, 本谷 雅代, 佐々木 茂, 仲瀬 裕志

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  129回・123回   41 - 41  2021.09

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 肝細胞癌の分子標的治療と概日時計の関連

  基盤研究(C)

  Project Year :

  2020.04

  -

  2023.03

   

  阿久津 典之, 佐々木 茂, 仲瀬 裕志

  　View Summary

  1. ヒト肝細胞癌における時計遺伝子発現の検討 肝細胞癌10症例の癌部および非癌部の組織よりRNAを作成しcDNAを合成。その後Comparative CT法を用いて相対的発現を解析した。Clock, Bmal1, Per1,Per2 Cry1の発現を癌部と非癌部で解析したところ、Per1およびPer2が癌部と非癌部で有意な発現の違いをあることが分かった。背景因子での違いがないかさらなる検 討を行っている。 2. 正常肝細胞および肝癌細胞株における時計遺伝子発現と炎症性サイトカインに対する反応 肝癌細胞株HepG2, Hep3B, HLE, HLF, HuH7, PLC/PRF/5のcDNAを用いて、Clock, Bmal1, Per1,Per2 Cry1の発現を解析し、細胞株間での発現に差があることがわ かり、Per1やPer2の発現が低い細胞株と、高い細胞株を用いて、種々の炎症性サイトカイン(IL-1β, IL-4, IL-13, TNF-α, IFN-γ, IL-10, TGF-β)の添加を行 い、RNAおよびタンパクを回収。時計遺伝子の変化を解析している。 3. 分子標的薬の正常肝細胞および肝癌細胞株における時計遺伝子の発現と炎症性サイトカインに対する反応 肝癌細胞株 (Hep3B, HLF, HuH7)にレンバチニブ1μMを投与 し、37°Cで48時間培養した後に、時計遺伝子Bmal1、Rev-erbα、Rev-erbβ、Per1、Per2、 Cry1の発現についてqPCR法、western blotting法を用い検討した。

• Effect of circadian clock on liver carcinogenesis based on non-alcoholic steatohepatitis

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2018.04

  -

  2021.03

   

  SASAKI SHIGERU

  　View Summary

  Fatty liver may lead to steatohepatitis, cirrhosis, and liver cancer. The main purpose of this study was to elucidate the cause of this pathological condition from the viewpoint of lifestyle differences, especially changes in circadian rhythms. We also want to clarify whether periodontal disease bacteria affect the intestinal flora and affect the formation of fatty liver and the exacerbation of fatty liver. Furthermore, we would like to clarify the effect of antibacterial agents against periodontal disease bacteria on fatty liver. From the results of this study, the effect of changes in circadian rhythm on fatty liver has not yet been clarified. We need to consider further.

• The role of HIF1 alfa in sorafenib resistant hepatocellular carcinoma

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2017.04

  -

  2020.03

   

  Akutsu Noriyuki

  　View Summary

  We hypothesized that the resistance of sorafenib treatment in hepatocellular carcinoma occurs by increasing PD-L1 expression that is directly enhanced by HIF1α. We cultured hepatocellular carcinoma cell lines using cobalt addition or a hypoxic chamber, and compared with control cell lines cultured under normoxia. HIF1α was upregulated in the culture with cobalt and hypoxia chamber. However, PD-L1 expression was not enhanced by either RT-PCR or Western blotting. PD-L1 expression was enhanced by adding IFNγ to hepatocellular carcinoma cell lines and was further enhanced by the addition of cobalt.