研究者詳細 - 田中　信悟

論文 - 田中　信悟

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Efficient implementation of hepatitis B surface antigen confirmatory neutralization tests.

Hitoshi Yonezawa, Shingo Tanaka, Makito Tanaka, Ryo Kobayashi, Satoshi Takahashi

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 1 ) 29 - 33 2024年01月 [国際誌]

INTRODUCTION: To prevent misreporting of false positives in the hepatitis B surface antigen (HBsAg) assay, it is recommended to confirm the low-positive cases with neutralization tests. However, currently not many facilities are implementing this due to the additional cost. The aim of this study was to clarify the risk factors for false positives in the high-sensitivity HBsAg quantitative tests to reduce the neutralization tests. METHODS: In this retrospective cohort study, we analyzed 47,305 patients who had their HBsAg value measured at Sapporo Medical University Hospital between November 2016 and March 2022. The patients eligible for the neutralization tests were those with HBsAg values between 0.005 and 1.000, even after reexamination by high-speed centrifugation. RESULTS: HBsAg quantitative tests were performed in 71,475 tests. Of these, 817 tests and 376 patients were subjected to neutralization tests. Of the patients who met the criteria, 329 were included in this study. Fifty-seven cases (17%) had negative results in the neutralization tests, suggesting false positives for the HBsAg assay. Multivariate analysis showed that younger age (adjusted odds ratio [aOR] 6.57), female sex (aOR 2.32), lower HBsAg values (aOR 59.6), and reagent improvement (aOR 2.06) were independent risk factors for false positives. The false-positive rate was actually high at 33.1% in the HBsAg range of 0.005-0.049 IU/mL and at 1.2% in the range above 0.050 IU/mL. CONCLUSIONS: Confirmatory neutralization tests should be performed at least in the range of 0.005-0.049 IU/mL where quantification is possible with a higher-sensitivity assay.

DOI PubMed

Synergistic antitumor effect of histone deacetylase class IIa inhibitor with lenvatinib in hepatocellular carcinoma.

Ryo Ito, Koji Miyanishi, Tomohiro Kubo, Kota Hamaguchi, Takahiro Osuga, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato

Hepatology international 17 ( 3 ) 735 - 744 2023年06月 [国際誌]

BACKGROUND: Histone deacetylase (HDAC) class I and IIa are highly expressed in hepatocellular carcinoma (HCC) and associated with decreased survival. However, clinically used pan and class I inhibitors have serious adverse events. In this study, we assessed the antitumor effects and tolerability of class IIa HDAC inhibitor (HDACI) with lenvatinib, which is a standard therapy for HCC. METHODS AND RESULT: Combination therapy with class IIa HDACI and lenvatinib exerted synergistic antitumor effect in human HCC cell lines. In mouse models, this therapy showed significant antitumor effects, and few adverse events occurred. In immunoblotting, the expression of fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) was high in cell lines that showed a high antitumor effect. In addition, class IIa HDACI administration decreased the expression of FGFR4. In the small interfering RNA (siRNA) analysis, knockdown of HDAC9, which is an isoform of HDAC class IIa, reduced the expression of FGFR4 and induced apoptosis. Immunohistochemistry of human clinical specimens showed a positivity rate of 32% for FGFR4 and 84% for HDAC9 in HCC, and all FGFR4-positive patients were HDAC9 positive. CONCLUSION: Class IIa HDACI and lenvatinib combination therapy induces apoptosis by downregulating FGFR4 and blocking the FGFR signaling in FGFR4-positive HCC cell lines and has demonstrated synergistic antitumor effects and safety. This combination therapy overcomes the problems of conventional therapies and will be beneficial for FGFR4-positive HCC patients.

DOI PubMed

Effect of albumin measurement methods on the albumin-bilirubin grade.

Makito Tanaka, Shingo Tanaka, Ema Suzuki, Ryo Kobayashi, Satoshi Takahashi

Annals of clinical biochemistry 60 ( 2 ) 100 - 108 2023年03月 [国際誌]

BACKGROUND: Albumin-bilirubin (ALBI) grade is an index of liver function based on total bilirubin (T-BIL) and albumin levels, and its usefulness has been widely reported. This study aimed to investigate the effect of different methods of measuring T-BIL and albumin levels on the ALBI grade in patients with liver disease. METHODS: In total, 170 patients from our hospital were included in this study. Correlations between T-BIL levels measured using the vanadate oxidation and enzymatic methods were analysed. Similarly, a correlation analysis of albumin levels between the bromocresol green (BCG) and modified bromocresol purple (BCP) methods was performed. Additionally, the ALBI grade was calculated for patients with liver disease, and the differences between each method of albumin measurement were compared. RESULTS: No differences were observed in the measured T-BIL values between the two methods. Contrastingly, the albumin levels of 100 random samples and 70 liver disease patients obtained using the modified BCP method were significantly lower than those measured using the BCG method. The rate of change in the modified ALBI grade between the BCG and BCP methods was 25.7%. CONCLUSIONS: Caution should be taken when comparing ALBI grades with those measured by other facilities because the method of albumin measurement can affect the ALBI grade. Standardization of albumin measurement is needed worldwide.

DOI PubMed

卒前腹部超音波検査実習における「腹部超音波検診判定マニュアル」の有用性について

田中信悟, 高橋聡, 加藤淳二

日本臨床検査医学会誌 ( (一社)日本臨床検査医学会 ) 70 ( 5 ) 369 - 372 2022年05月

腹部超音波検査実習の学習資料として、マニュアルの有用性について検討した。選択臨床実習で当講座を選択し、腹部超音波検査実習を行った医学部6年生12名を対象とした。マニュアルの記録断面例5断面の描出による実技試験(5点満点)については5点が11名、4点が1名、病変画像5枚についての口頭試問(5点満点)は5点が7名、4点が5名であった。アンケート調査結果について、記録断面例の描出では右肋間走査での胆嚢・肝臓の描出および膵の描出で習熟度がやや低い傾向を認めたが、他部位の描出の習熟度はおおむね良好であった。マニュアル実施基準の理解度は平均3.8点、12名中11名が学習資料としてマニュアルは適切であるとの意見であった。マニュアルを学習資料とした腹部超音波検査実習により基本的走査法のみならず、医学生として十分な基礎的知識が得られたと考えられた。

Association between Hepatic Oxidative Stress Related Factors and Activation of Wnt/β-Catenin Signaling in NAFLD-Induced Hepatocellular Carcinoma.

Kota Hamaguchi, Koji Miyanishi, Takahiro Osuga, Shingo Tanaka, Ryo Ito, Hiroki Sakamoto, Tomohiro Kubo, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Toru Mizuguchi, Ichiro Takemasa, Junji Kato

Cancers 14 ( 9 ) 2022年04月 [国際誌]

We investigated the association between iron overload, oxidative stress (8-oxo-7,8-dihydroguanine: 8-oxo-dG scores), Wnt/β-catenin pathway activation (expression of glutamine synthetase: GS), and tumor hyperintensity in the Gd-EOB-DTPA-enhanced MRI hepatobiliary phase (relative enhancement ratio: RER). This was a retrospective analysis of 94 hepatocellular carcinoma (HCC) patients who underwent surgical resection. In HBV-, HCV-, and alcohol-associated HCC, serum ferritin levels in the high and low RER groups were equivalent. In contrast, ferritin levels were elevated in the 'high RER' group of patients with nonalcoholic fatty liver disease (NAFLD)-HCC. As predictors of GS positivity, high RER had a sensitivity of 57.2% and a specificity of 100%. High serum ferritin had a sensitivity of 85.7% and a specificity of 85.7%. All cases with serum ferritin ≥275.5 ng/mL and high RER were 8-oxo-dG- and iron staining-positive. Additionally, GS positivity was seen in all cases with "serum ferritin levels above the upper limits or iron staining-positive" and '8-oxo-dG high' cases. Therefore, combining serum ferritin levels with RER may increase the accuracy with which activated Wnt/β-catenin signaling is predicted in NAFLD-HCC. We suggest that 8-oxo-dG accumulates following increased oxidative stress due to hepatic tissue iron deposition; this may activate Wnt/β-catenin signaling and trigger carcinogenesis.

DOI PubMed

A case of acute exacerbation of chronic hepatitis C during the course of adrenal Cushing's syndrome

Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Junji Kato

Clinical Case Reports ( Wiley ) 10 ( 2 ) e05337 2022年02月 [国際誌]

DOI PubMed

A Case of Unresectable Combined Hepatocellular-Cholangiocarcinoma Successfully Treated with Lenvatinib.

Takahiro Osuga, Koji Miyanishi, Ryo Ito, Shingo Tanaka, Kota Hamaguchi, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Taro Sugawara, Shintaro Sugita, Ichiro Takemasa, Tadashi Hasegawa, Junji Kato

Case reports in oncology 15 ( 1 ) 318 - 325 2022年 [国際誌]

A 77-year-old man was referred to our hospital because of a hepatic tumor. Blood biochemistry showed elevated serum alfa-fetoprotein, protein induced by vitamin K absence-II, and carbohydrate antigen 19-9 levels. Gd-EOB-DTPA-enhanced magnetic resonance imaging revealed a 95-mm-sized tumor in liver S7. The tumor showed heterogeneous hyperintensity in the arterial phase, slightly washed out from the portal vein phase, and hypointensity in the hepatocellular phase. Post-enlargement segmental resection was performed, and the pathological diagnosis was combined hepatocellular cholangiocarcinoma. Seven months after surgery, multiple liver tumors were found, and biopsy revealed combined hepatocellular-cholangiocarcinoma. Hepatic arterial infusion chemotherapy with cisplatin was initiated. However, the patient developed a pulmonary abscess, which was treated with antibiotics. He then underwent treatment with lenvatinib, 11 months after surgery. At 8 weeks follow-up, a complete response (according to the modified Response Evaluation Criteria in Solid Tumors [RECIST]) and a partial response (RECIST version 1.1) was noted. To the best of our knowledge, thus far, only a single case of lenvatinib treatment of unresectable mixed liver cancer has been reported. In that case, lenvatinib was used as a third-line treatment. The present report is the first to describe lenvatinib as a first-line therapy for unresectable combined hepatocellular-cholangiocarcinoma, which resulted in a meaningful response. This case provides useful insights into the choice of appropriate drug treatment in this disease in the absence of randomized controlled trials of drug treatment.

DOI PubMed

MUTYH is associated with hepatocarcinogenesis in a non-alcoholic steatohepatitis mouse model

Hiroki Sakamoto, Koji Miyanishi, Shingo Tanaka, Ryo Ito, Kota Hamaguchi, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Takahiro Osuga, Kazuyuki Murase, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

Scientific Reports ( Springer Science and Business Media LLC ) 11 ( 1 ) 3599 - 3599 2021年12月 [国際誌]

AbstractNon-alcoholic steatohepatitis (NASH)-related HCC is associated with oxidative stress. However, the mechanisms underlying the development of NASH-related HCC is unclear. MUTYH is one of the enzymes that is involved in repair of oxidative DNA damage. The aim of this study was to investigate the association between MUTYH and NASH-related hepatocarcinogenesis. MUTYH wild-type (Mutyh^+/+), heterozygous (Mutyh^+/−), and MUTYH-null (Mutyh^−/−) mice were fed a high-fat high-cholesterol (HFHC) diet or HFHC + high iron diet (20 mice per group) for 9 months. Five of 20 Mutyh^−/− mice fed an HFHC + high iron diet developed liver tumors, and they developed more liver tumors than other groups (especially vs. Mutyh^+/+ fed an HFHC diet, P = 0.0168). Immunohistochemical analysis revealed significantly higher accumulation of oxidative stress markers in mice fed an HFHC + high iron diet. The gene expression profiles in the non-tumorous hepatic tissues were compared between wild-type mice that developed no liver tumors and MUTYH-null mice that developed liver tumors. Gene Set Enrichment Analysis identified the involvement of the Wnt/β-catenin signaling pathway and increased expression of c-Myc in MUTYH-null liver. These findings suggest that MUTYH deficiency is associated with hepatocarcinogenesis in patients with NASH with hepatic iron accumulation.

DOI PubMed

Combination of psoas muscle mass index and neutrophil/lymphocyte ratio as a prognostic predictor for patients undergoing nonsurgical hepatocellular carcinoma therapy

Yusuke Sugama, Koji Miyanishi, Takahiro Osuga, Shingo Tanaka, Kota Hamaguchi, Ryo Ito, Hiroki Sakamoto, Tomohiro Kubo, Hiroyuki Ohnuma, Kazuyuki Murase, Kohich Takada, Masayoshi Kobune, Junji Kato

JGH Open ( Wiley ) 5 ( 12 ) 1335 - 1343 2021年12月 [国際誌]

BACKGROUND AND AIM: Reliable predictors for hepatocellular carcinoma (HCC) are urgently needed. The psoas muscle index (PMI) is a simple and rapid method for evaluating muscle atrophy. Furthermore, the neutrophil/lymphocyte ratio (NLR) is a prognostic factor that is easy to calculate in everyday clinical practice. We aimed to investigate the value of the PMI and NLR as prognostic factors for patients receiving nonsurgical HCC therapy, hepatic arterial infusion chemotherapy (HAIC), transcatheter arterial chemoembolization (TACE), or molecular targeted drugs such as sorafenib (SOR) and lenvatinib (LEN). METHODS: We enrolled 87 patients with HCC who were treated with HAIC, TACE, SOR, or LEN. The primary endpoint was overall survival (OS) with variable PMI or NLR status. For Barcelona Clinic Liver Cancer (BCLC)-B patients, useful prognostic factors were examined by comparing the OS between stratified groups. Prognostic factors including PMI and NLR were evaluated by univariate and multivariate analysis. RESULTS: Analysis of HAIC or TACE (HAIC/TACE) and SOR or LEN (SOR/LEN) patients showed significant differences in OS between low and high PMI. In patients treated with TACE, there was a significant difference in OS between low and high NLR. For BCLC-B and low PMI, the prognosis was significantly worse for SOR/LEN than for TACE, although there was no difference for high PMI, suggesting that PMI may be useful for treatment selection. In addition, the prognostic formula composed of PMI, NLR, and up-to-seven criteria developed in the present study may be useful. CONCLUSION: PMI and NLR are considered to be independent prognostic factors for HCC.

DOI PubMed

当院におけるアルブミン製剤の適正使用について

田中信悟, 村井良精, 田中真輝人, 北山育実, 片山雄貴, 木次谷玲那, 盛合美加子, 遠藤明美, 淺沼康一, 遠藤輝夫, 高橋聡, 加藤淳二

日本臨床検査医学会誌 ( (一社)日本臨床検査医学会 ) 69 ( 12 ) 903 - 908 2021年12月

当院で2019年にアルブミン製剤が投与された436症例(男260例、女176例、年齢中央値67歳)、投与回数1808回を対象に、アルブミン製剤の適正使用について検討した。1808回中1748回(96.7%)で投与前にアルブミン値が測定されていた。アルブミン製剤の1回使用量は25g以下が93.4%、50g以上の使用は3.7%にみられた。適応病態別の投与回数は出血性ショック20回、敗血症・循環血漿量減少266回、人工心肺を使用する心臓手術84回、肝硬変131回、ネフローゼ12回、体外循環実施時39回、血漿交換70回、重症熱傷45回、肺水腫・浮腫1141回で、明らかな不適切使用はみられなかった。「使用指針」遵守率は出血性ショックで70%、低蛋白に起因する肺水腫・浮腫で77%、人工心肺を使用する心臓手術で87%、ネフローゼで92%、敗血症・循環血漿量減少で94%であった。他の病態では100%遵守されていると判断された。

他の施設から得られた不規則抗体情報の有用性に関する検討

村井良精, 遠藤輝夫, 盛合美加子, 片山雄貴, 遠藤明美, 淺沼康一, 田中信悟, 高橋聡

医学検査 ( (一社)日本臨床衛生検査技師会 ) 70 ( 4 ) 773 - 777 2021年10月

当院での輸血症例のうち、他施設から不規則抗体情報が得られた症例を抽出し、当院での輸血対応に有用であったかを後方視的に検証した。全7例の情報源は、前医からの診療情報提供書6例、不規則抗体情報カード保有1例であった。他施設から情報を得る利点として、結果報告あるいは対応決定までの時間短縮、市販試薬では同定困難であり、然るべき施設に検査依頼すべきかの判断に結びつくまでの時間短縮、抗体消失に起因する遅発性溶血性輸血反応(delayed hemolytic transfusion reaction:DHTR)の防止が考えられた。一方、情報伝達方法および受領後の活用法が統一されておらず、情報と検査結果が乖離した場合の判断に苦慮する場合などの課題も明らかになった。また今回の検討から、厚生労働省の統針にある「患者が携帯する不規則抗体カード」の普及が進んでいないことが推測された。今後、これらの課題が克服されることで、より安全な輸血医療に結びつくことが望まれる。(著者抄録)

Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study.

Hitoshi Yonezawa, Shingo Tanaka, Momoko Furuya, Koji Yamada, Koichi Asanuma, Yoshihiro Fujiya, Koji Miyanishi, Satoshi Takahashi, Junji Kato

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 10 ) 1454 - 1458 2021年10月 [国際誌]

INTRODUCTION: In quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases. METHODS: In this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation. RESULTS: In total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010). CONCLUSIONS: Patients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.

DOI PubMed

Programmed cell death ligand 1 expression in a case of poorly differentiated lymphocyte‐rich hepatocellular carcinoma

Ginji Omori, Takahiro Osuga, Koji Miyanishi, Kota Hamaguchi, Shingo Tanaka, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Yasuhiro Kikuchi, Toshihiko Torigoe, Junji Kato

Clinical Case Reports ( Wiley ) 9 ( 9 ) e04764 2021年09月 [国際誌]

DOI PubMed

進行性腎細胞癌に対するスニチニブ治療に伴う左室壁運動異常の出現様式

安井謙司, 湯田聡, 大井由紀子, 橋本浩平, 市原浩司, 柳原希美, 田中信悟, 永原大五, 高橋聡

臨床泌尿器科 ( (株)医学書院 ) 75 ( 2 ) 151 - 156 2021年02月

＜文献概要＞進行性腎細胞癌患者に対するスニチニブ治療後,がん治療関連心機能障害(CTRCD)に至る前の段階で左室壁運動低下が出現するか否か,およびその部位を検討した.スニチニブ治療前後で経胸壁心エコー図検査を施行した進行性腎細胞癌患者16例を対象とし,左室壁運動異常の有無と左室駆出率(LVEF)を評価した.16例中6例(38%)に左室壁運動異常を認めた.そのうちCTRCDは4例で,2例はその定義を満たさなかった.壁運動異常の出現様式はびまん性,心尖部の壁運動低下,後壁と下壁および心尖部の壁運動低下とさまざまであった.CTRCDの定義を満たさない段階でも,左室壁運動異常が出現していた.スニチニブ治療開始後にはLVEFのみではなく左室壁運動異常にも留意する必要があると考えられた.

A case of hypervascular tumors in the liver and pancreas: synchronous hepatocellular carcinoma and pancreatic metastasis from renal cell carcinoma 36 years after nephrectomy

Hajime Nakamura, Shingo Tanaka, Koji Miyanishi, Yutaka Kawano, Takahiro Osuga, Kazuma Ishikawa, Makoto Yoshida, Hiroyuki Ohnuma, Kazuyuki Murase, Kohichi Takada, Hiroshi Yamaguchi, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Junji Kato

Clinical Case Reports ( Wiley ) 9 ( 2 ) 932 - 937 2020年12月 [国際誌]

担当区分：責任著者

DOI PubMed

高感度HBsAg測定試薬の改良による偽陽性抑制効果の検討

米澤仁, 田中信悟, 八鍬佑貴, 高橋聡

感染症学雑誌 ( (一社)日本感染症学会 ) 94 ( 1 ) 97 - 101 2020年01月 [査読有り]

近年,高感度HBs抗原測定試薬が開発され,その有用性が報告されている.しかし,その高感度化の弊害として特異性の低下(偽陽性)が危惧されている.偽陽性を避けるため,低値陽性例にはHBs抗体を用いた抑制試験でその真偽を確認することが推奨されているが,実施している施設は多くない.従って,高感度HBs抗原測定試薬を導入しているが抑制試験を実施していない施設では,HBs抗原偽陽性例が増加している可能性がある.2018年4月,特異性の向上を目的として高感度HBs抗原測定試薬「ルミパルスプレストHBsAg-HQ」の改良が行われた.今回,本試薬の性能について検討を行ったので報告する.対象は改良前「ルミパルスプレストHBsAg-HQ」にて偽陽性と判定された7検体とした.本検討における偽陽性の基準は「HBs抗原定量値がカットオフ(0.005IU/mL)以上かつ抑制試験にて陰性」とした.測定には全自動化学発光酵素免疫測定システム「ルミパルスL2400」を使用した.改良後試薬を用いてHBs抗原値を測定した結果,改良前試薬で偽陽性とされた7検体中5検体でHBs抗原はカットオフ値(0.005IU/mL)未満であった.検出限界は0.0015IU/mLであり,改良前と比較して同等であった.偽陽性の原因として非特異反応の可能性について検討したところ,標識アルカリフォスファターゼに対する非特異反応と考えられる検体を認めた.改良前試薬での測定期間における月別偽陽性発生率は平均0.26%であったが,改良後試薬へ移行後は平均0.09%と低下傾向を認めた.以上から,改良後「ルミパルプレストスHBsAg-HQ」を用いることで偽陽性率の低下が期待でき,抑制試験数および偽陽性の「誤報告」を減少できる可能性がある.(著者抄録)

小型混合型肝癌の1例

大須賀崇裕, 宮西浩嗣, 田中信悟, 中村元, 坂本拡基, 大沼啓之, 村瀬和幸, 高田弘一, 小船雅義, 加藤淳二, 永山稔, 木村康利, 竹政伊知朗, 辻脇光洋, 長谷川匡

肝臓 ( (一社)日本肝臓学会 ) 60 ( 8 ) 294 - 301 2019年08月 [査読有り]

症例は56歳男性。B型肝硬変とアルコール性肝障害で当科通院中。2017年7月のEOB-MRIにて肝S4に多血性腫瘍を認められ入院。採血検査では、肝硬変による肝トランスアミナーゼ上昇、血小板減少を認めたが、腫瘍マーカーは陰性であった。EOB-MRIでは、腫瘍は10mm大で早期相で不均一な高信号、肝細胞相で低信号、拡散強調画像で高信号を呈した。肝細胞癌(HCC)Stage1と診断し、腹腔鏡下肝部分切除術を施行した。術後16ヵ月経過し再発は認めていない。病理学的に腫瘍は高分化型HCC、中分化型HCC、HCCと肝内胆管癌の移行部、高-中分化型肝内胆管癌の4領域で構成される混合型肝癌であった。本症例は小型の段階で、HCCの一部が胆管細胞癌へ脱分化又は形質転換した非常に初期の混合型肝癌と考えられた。(著者抄録)

新規ガストリン放出ペプチド前駆体測定系における測定値安定性についての検討

小林亮, 高橋祐輔, 田中信悟, 柳原希美, 淺沼康一, 高橋聡

臨床化学 ( (一社)日本臨床化学会 ) 48 ( 3 ) 232 - 238 2019年07月 [査読有り]

ガストリン放出ペプチド前駆体(ProGRP)の従来試薬での血清の測定値は経時的に減少することが知られている。そこで、トロンビンの作用部位と異なる位置でProGRPを認識する抗体を測定原理とするエクルーシス試薬ProGRPが開発された。我々が以前行った、この新試薬における検討において、血清の測定値安定性は血漿と同等に得ることができなかった。そこで今回、健常者10人の血清検体にProGRP(31-98)を添加し、室温および4℃保存でのProGRP濃度を経過時間毎に測定した。平均残存率は検体分離後から72時間で約10%低下し、測定値低下の再現性が確認された。測定値の低下がトロンビンに起因するか否かを添加回収試験により調べた結果、トロンビンの影響を受けていないことが確認された。各種プロテアーゼインヒビターの添加試験ではアプロチニンとロイペプチンによる分解阻害効果が認められた。本検討によって、試料採取から何時間まで血清ProGRP値が血漿と同様に評価可能であるか示された。また、血清での測定値不安定性の原因として、セリンプロテアーゼの関与が示唆された。(著者抄録)

Changes of tight junction and interleukin-8 expression using a human gastroid monolayer model of Helicobacter pylori infection.

Takahiro Uotani, Kosuke Murakami, Tomohisa Uchida, Shingo Tanaka, Hiroyuki Nagashima, Xi-Lei Zeng, Junko Akada, Mary K Estes, David Y Graham, Yoshio Yamaoka

Helicobacter 24 ( 3 ) e12583 2019年06月 [査読有り] [国際誌]

BACKGROUND: Lack of a model that mirrors Helicobacter pylori-induced gastric mucosal inflammation has hampered investigation of early host-bacterial interactions. We used an ex vivo model of human stomach, gastric epithelial organoid monolayers (gastroid monolayers) to investigate interactions of H pylori infection and the apical junctional complex and interleukin-8 (IL-8) expression. METHOD: Morphology of human antral mucosal gastroid monolayers was evaluated using histology, immunohistochemical (IHC) staining, and transmission electron microscopy (TEM). Functional and gross changes in the apical junctional complexes were assessed using transepithelial electrical resistance (TEER), cytotoxicity assays, and confocal laser scanning microscopy. IL-8 expression was evaluated by real-time quantitative PCR and ELISA. RESULTS: When evaluated by IHC and TEM, the morphology of gastroid monolayers closely resembled in vivo human stomach. Following inoculation of H pylori, TEER transiently declined (up to 51%) in an H pylori density-dependent manner. TEER recovered by 48 hours post-infection and remained normal despite continued presence and replication of H pylori. Confocal scanning microscopy showed minimal disruption of zonula occludens-1 or E-cadherin structure. IL-8 production was unchanged by infection with either CagA-positive or CagA-negative H pylori and JNK and MEK inhibitors did not suppress IL-8 production, whereas p38 and IKK inhibitor significantly did. CONCLUSION: Human gastroid monolayers provide a model for experimental H pylori infection more consistent with in vivo human infections than seen with typical gastric epithelial cell lines. This ex vivo system should lead to better understanding of H pylori host-pathogen interactions.

DOI PubMed

Successful Treatment of Hepatocellular Carcinoma with Transcatheter Arterial Chemoembolization followed by Radical Liver Transplantation in a Patient with Severe Liver Damage

Hajime Nakamura, Yutaka Kawano, Koji Miyanishi, Kazuma Ishikawa, Tomohiro Kubo, Shingo Tanaka, Kohichi Takada, Masayoshi Kobune, Kohei Harada, Norio Kawamura, Tsuyoshi Shimamura, Hiromi Kanno-Okada, Junji Kato

Case Reports in Oncology ( S. Karger AG ) 12 ( 1 ) 289 - 296 2019年04月 [査読有り] [国際誌]

Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage.

DOI PubMed

The role of iron in hepatic inflammation and hepatocellular carcinoma.

Miyanishi K, Tanaka S, Sakamoto H, Kato J

Free radical biology & medicine ( Elsevier BV ) 133 200 - 205 2019年03月 [査読有り] [国際誌]

Iron is an essential for organisms and the liver plays a major role in its storage. In pathologic conditions, where iron absorption from the intestine or iron uptake into the hepatocytes is increased, excess iron accumulates in the hepatocytes, leading to hepatocyte injury through the production of free radicals. Iron exerts its toxicity by catalyzing the generation of reactive oxygen species (ROS). ROS causes cell injury by inducing damage to the lysosomal, cytoplasmic, nuclear and mitochondrial membranes, apoptosis through activation of the caspase cascade, and hyperoxidation of fatty chains. In this manuscript, we reviewed the articles regarding role of iron in hepatic inflammation and hepatocellular carcinoma.

DOI PubMed

ルミパルスプレストPIVKAII-Nエーザイにおける基本性能の評価

古谷桃子, 山田浩司, 菅原清美, 淺沼康一, 田中信悟, 永原大五, 柳原希美, 高橋聡

医学検査 ( (一社)日本臨床衛生検査技師会 ) 68 ( 1 ) 56 - 60 2019年01月 [査読有り]

PIVKA-IIは、ビタミンK欠乏、ビタミンK拮抗薬投与、肝実質障害などで産生され、特に、肝細胞癌を有する患者血清中に高率に出現することから、腫瘍マーカーとして使用されている。今回、MU-3抗体(1次抗体)を用いた測定試薬で、新たに2次抗体をポリクローナル抗体からモノクローナル抗体に変更し、さらに、血漿測定も可能として発売された「ルミパルスプレストPIVKA II-Nエーザイ」が発売されたので、その基本的性能について検討した。その結果、同時再現性はCV値で1.8〜6.3%、日差再現性はCV値で2.9〜5.4%、希釈直線性についても概ね良好であった。現行試薬との相関性はy=0.95x+117.2、r=0.99と良好であり、本試薬における血清検体と血漿検体の相関性はy=0.78x+231.4、r=1.00と傾きがやや低い傾向だったが、測定上限を10,000mAU/mLに設定して解析すると傾き1.04と良好な結果が得られた。以上の結果から本試薬は日常検査に有用と考えられた。(著者抄録)

A case of small combined hepatocellular-cholangiocellular carcinoma

Takahiro Osuga, Koji Miyanishi, Shingo Tanaka, Hajime Nakamura, Hiroki Sakamoto, Hiroyuki Onuma, Kazuyuki Murase, Koichi Takada, Masayoshi Kobune, Junji Kato, Minoru Nagayama, Yasutoshi Kimura, Ichiro Takemasa, Mitsuhiro Tsujiwaki, Tadashi Hasegawa

Acta Hepatologica Japonica ( Japan Society of Hepatology ) 60 ( 8 ) 294 - 301 2019年

A 56-year-old man who had been visiting our hospital for type B cirrhosis since 1988 was admitted for the treatment of hepatic tumor that was detected using an EOB-MRI study in July 2017. Blood test showed elevated aminotransferase and thrombocytopenia due to liver cirrhosis however, tumor markers were negative. In CT during angiography, CTAP showed low absorption, and CTHA showed heterogeneously high absorption. We diagnosed the tumor as hepatocellular carcinoma, followed by a laparoscopic partial resection of the liver. In 16 months after surgery, there was no recurrence. As per the pathological findings, the tumor consisted of (1) well-differentiated hepatocellular carcinoma component, (2) moderately-differentiated hepatocellular carcinoma component, (3) transitional portion between hepatocellular carcinoma and intrahepatic cholangiocarcinoma, and (4) intrahepatic cholangiocarcinoma component. Thus, the tumor was diagnosed as classical type combined hepatocellular-cholangiocellular carcinoma as per the WHO classification. It was suggested that dedifferentia-tion and transformation occurred in the untreated small hepatocellular carcinoma.

DOI

An intronic single nucleotide polymorphism in the MUTYH gene is associated with increased risk for HCV-induced hepatocellular carcinoma.

Akira Sakurada, Koji Miyanishi, Shingo Tanaka, Masanori Sato, Hiroki Sakamoto, Yutaka Kawano, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato

Free radical biology & medicine 129 88 - 96 2018年12月 [査読有り] [国際誌]

BACKGROUND & AIMS: The role of base excision repair genes in human hepatocarcinogenesis has not yet been explored. Here, we investigated relationships between variants of these genes and the risk of developing hepatocellular carcinoma (HCC). METHODS: Nineteen tagging SNPs in base excision repair genes (including MUTYH, OGG1 and MTH1) were genotyped using iPLEX assays; one significant SNP was found and confirmed in Japanese patients with chronic hepatitis C (CHC) (n = 38 HCC and 55 controls). The effects of modifying the intronic variants were determined by luciferase assays. MUTYH-null mice were used to examine the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis. RESULTS: Significant associations were found for a single intron SNP (rs3219487) in the MUTYH gene. The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (OR = 9.27, 95% CI = 2.39 -32.1, P = 0.0005). MUTYH mRNA levels in both peripheral mononuclear cells were significantly lower in G/A or A/A genotyped subjects (P = 0.0157 and 0.0108, respectively). We found that -2000 in the MUTYH promoter region is involved in enhanced expression of MUTYH by insertion of a major allele sequence of rs3219487. Liver tumors were observed in MUTYH-null mice after 12 months´ high iron diet, but no tumors developed when dietary anti-oxidant (N-Acetyl-L-cysteine) was also provided. CONCLUSIONS: CHC patients with the rs3219487 adenine allele had a significantly increased risk of developing HCC. MUTYH-null mice with iron-associated oxidative stress were susceptible to development of liver tumors unless prevented by dietary anti-oxidants.

DOI PubMed

Clostridium difficile肝膿瘍の1例

松野鉄平, 田中信悟, 宮西浩嗣, 河野豊, 中村元, 坂本拡基, 早坂尚貴, 石川和真, 村瀬和幸, 高田弘一, 高梨訓博, 勝木伸一, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 59 ( 3 ) 180 - 186 2018年03月

症例は68歳、男性。発熱、心窩部痛を主訴に近医を受診し、肝膿瘍、播種性血管内凝固症候群(DIC)、門脈血栓症と診断され当院へ転院となった。前医にてメロペネムが投与されるも改善傾向を認められなかったが、当院入院時の血液培養検査にてClostridium difficile(C.difficile)が検出され、メトロニダゾール内服を開始したところ速やかに改善した。肝膿瘍および便からもC.difficileが検出され、PCR-rebotypingで全て同一菌株と同定された。血液培養検査でC.difficileが検出されたため早期にメトロニダゾールの投与を開始でき、治癒が得られた肝膿瘍症例を経験した。広域抗菌薬に対する反応が悪い肝膿瘍に対しては、原因菌としてC.difficileも念頭に診断・治療を進めることが必要である。(著者抄録)

DOI

Increased Duodenal Iron Absorption through Upregulation of Ferroportin 1 due to the Decrement in Serum Hepcidin in Patients with Chronic Hepatitis C.

Sato M, Miyanishi K, Tanaka S, Sakurada A, Sakamoto H, Kawano Y, Takada K, Kobune M, Kato J

Canadian journal of gastroenterology & hepatology 2018 2154361 2018年 [査読有り]

DOI PubMed

Interleukin-17C in Human Helicobacter pylori Gastritis

Shingo Tanaka, Hiroyuki Nagashima, Modesto Cruz, Tomohisa Uchida, Takahiro Uotani, Jose A. Jimenez Abreu, Varocha Mahachai, Ratha-korn Vilaichone, Thawee Ratanachu-ek, Lotay Tshering, David Y. Graham, Yoshio Yamaoka

INFECTION AND IMMUNITY ( AMER SOC MICROBIOLOGY ) 85 ( 10 ) 2017年10月 [査読有り]

担当区分：筆頭著者

The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of I kappa B kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pyloriinduced diseases remains to be determined.

DOI PubMed

Autophagy-related genes in Helicobacter pylori infection

Shingo Tanaka, Hiroyuki Nagashima, Takahiro Uotani, David Y. Graham, Yoshio Yamaoka

HELICOBACTER ( WILEY ) 22 ( 3 ) 2017年06月 [査読有り]

BackgroundIn vitro studies have shown that Helicobacter pylori (H.pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H.pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H.pylori infection are not yet fully understood. Materials and MethodsWe analyzed autophagy-related gene expression in H.pylori-infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H.pylori infection. ResultsMicroarray analysis of 226 autophagy-related genes showed that 16 genes were upregulated (7%) and nine were downregulated (4%). We used quantitative reverse transcriptase polymerase chain reaction to measure mRNA levels of the downregulated genes (ATG16L1, ATG5, ATG4D, and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H.pylori-positive specimens (n=86) were significantly less than those in H.pylori-negative specimens (n=50). ATG16L1 mRNA levels were inversely related to H.pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H.pylori-positive and 77 H.pylori-negative subjects. The odds ratio for the presence of H.pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes. ConclusionsAutophagy-related gene expression profiling using high-throughput microarray analysis indicated that downregulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H.pylori in gastric epithelial cells.

DOI PubMed

集学的治療により救命し得たClostridium perfringensによる肝膿瘍の2例

久保智洋, 河野豊, 宮西浩嗣, 石川和真, 桜田晃, 佐藤昌則, 保木寿文, 田村文人, 田中信悟, 高田弘一, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 58 ( 2 ) 105 - 114 2017年02月

症例1は50歳男性。微熱、下痢、倦怠感と意識障害のため当科を紹介受診した。溶血、肝障害、腎障害を合併しており、膿瘍内容のグラム染色にてClostridium perfringens(以下C.perfringens)によるガス産生性肝膿瘍と考えられた。抗菌薬および透析、血漿交換、エンドトキシン吸着にて容態は改善し、第38病日に退院した。症例2は77歳女性。発熱、嘔吐と意識障害のため当科紹介受診した。溶血、肝障害、腎障害を合併しており、膿瘍内容のグラム染色にてC.perfringensによるガス産生性肝膿瘍と考えられた。集学的治療にて容態は改善し、第28病日に退院した。C.perfringensによる肝膿瘍は急激な経過をたどることが多く、死亡率が極めて高い。グラム染色による短時間での起因菌の推定により、集学的治療の早期介入が救命に寄与したものと考えられた。(著者抄録)

DOI

Prostate stem cell antigen gene TT genotype and development of intestinal metaplasia in Helicobacter pylori infection

Takahiro Uotani, Mitsushige Sugimoto, Hitomi Ichikawa, Shingo Tanaka, Hiroyuki Nagashima, Tomohisa Uchida, David Y. Graham, Yoshio Yamaoka

JOURNAL OF DIGESTIVE DISEASES ( WILEY-BLACKWELL ) 17 ( 1 ) 20 - 27 2016年01月 [査読有り]

ObjectivesGastric cancer is etiologically related to interactions between Helicobacter pylori (H. pylori) infection, environmental and host factors. Gastric carcinoma is associated with a cascade of increasing atrophic gastric mucosal damage. Prostate stem cell antigen (PSCA) polymorphisms have been associated with an increased risk of gastric cancer. We aimed to examine the interaction between PSCA polymorphisms and H. pylori in the progression of H. pylori-related gastritis. MethodsThe genotypes (TT, TC and CC) of PSCA single nucleotide polymorphism rs2294008 among H. pylori infected and uninfected Bhutanese were compared with the severity of H. pylori-related gastritis [neutrophils, monocytes, atrophy scores, H. pylori density, and the presence and extent of intestinal metaplasia (IM)] using the updated Sydney system. ResultsBiopsies from 339 participants were included. The proportion of biopsies with IM was significantly (P< 0.05) greater in those with the TT genotype than in either those with the CT or CC genotype. Although no significant differences were found in inflammation or H. pylori density scores, the scores for IM at both gastric corpus and antrum among participants infected by H. pylori with the TT genotype was significantly (P < 0.05) greater than in the C allele carriers. ConclusionPSCA TT genotype is associated with a more than a threefold increase in the prevalence and the extent of gastric mucosal IM compared to C allele carriers among H. pylori-infected Bhutanese.

DOI PubMed

Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis

Toshifumi Hoki, Koji Miyanishi, Shingo Tanaka, Kohichi Takada, Yutaka Kawano, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Masayoshi Kobune, Junji Kato

HEPATOLOGY ( WILEY-BLACKWELL ) 62 ( 3 ) 751 - 761 2015年09月 [査読有り] [国際誌]

Increased hepatic iron accumulation is thought to be involved in the pathogenesis of nonalcoholic steatohepatitis (NASH). Hepatic iron accumulation, as well as oxidative DNA damage, is significantly increased in NASH livers. However, the precise mechanism of iron accumulation in the NASH liver remains unclear. In this study, 40 cases with a diagnosis of NASH (n=25) or simple steatosis (SS; n=15) by liver biopsy were enrolled. An oral iron absorption test (OIAT) was used, in which 100 mg of sodium ferrous citrate was administered to each individual. The OIAT showed that absorption of iron from the gastrointestinal (GI) tract was increased significantly in NASH patients, compared to SS and control subjects. Iron reduction therapy was effective in patients with NASH, who exhibited iron deposition in the liver and no alanine aminotransferase improvement after other therapies (n=9). Serum hepcidin concentration and messenger RNA (mRNA) levels of divalent metal transporter 1 (DMT1) also were significantly elevated in patients with NASH. OIAT results were correlated with grade of liver iron accumulation and DMT1 mRNA levels. Then, we demonstrated that DMT1 mRNA levels increased significantly in Caco-2/TC7 cell monolayers cultured in transwells with serum from NASH patients. An electrophoresis mobility shift assay showed activation of iron regulatory protein (IRP) in those cells, and IRP1 small interfering RNA clearly inhibited the increase of DMT1 mRNA levels. Conclusion: In spite of elevation of serum hepcidin, iron absorption from the GI tract increased through up-regulation of DMT1 by IRP1 activation by humoral factor(s) in sera of patients with NASH. (Hepatology 2015) Hepatology 2015;62:751-761)

DOI PubMed

Prevention of hepatocellular carcinoma: Focusing on antioxidant therapy

Koji Miyanishi, Toshifumi Hoki, Shingo Tanaka, Junji Kato

World Journal of Hepatology ( Baishideng Publishing Group Co ) 7 ( 3 ) 593 - 599 2015年 [査読有り] [国際誌]

Oxidative stress has been investigated in the context of alcoholic liver injury for many years and shown to be a causal factor of chronic hepatitis C (CHC), nonalcoholic steatohepatitis (NASH), drug-induced liver injury, Wilson' s disease, and hemochromatosis. In CHC, it has been demonstrated that oxidative stress plays an important role in hepatocarcinogenesis. In cases with persistent hepatitis due to failure of hepatitis C virus eradication, or chronic liver disease, such as NASH, the treatment of which remains unestablished, it is important to reduce serum alanine aminotransferase levels and prevent liver fibrosis and development of hepatocellular carcinoma. This also suggests the importance of antioxidant therapy. Among treatment options where it would be expected that anti-inflammatory activity plays a role in their confirmed efficacy for chronic hepatitis, iron depletion therapy, glycyrrhizin, ursodeoxycholic acid, Sho-Saiko-To, and vitamin E can all be considered antioxidant therapies. To date, however, the ability of these treatments to prevent cancer has been confirmed only in CHC. Nevertheless, anti-inflammatory and antifibrotic effects have been demonstrated in other liver diseases and these therapies may potentially be effective for cancer prevention.

DOI PubMed

Clinical Significance of Adjuvant Surgical Resection for Initially Unresectable Pancreatic Cancer Responsive to Arterial Infusion Chemotherapy

Tadashi Doi, Hisato Homma, Takehide Akiyama, Shinichi Mezawa, Minoru Takahashi, Motoo Ohi, Shingo Tanaka, Kazuhiro Morii, Katsuhisa Kogawa, Motoya Takeuchi, Kenichirou Hirata, Satoshi Hirano

HEPATO-GASTROENTEROLOGY ( H G E UPDATE MEDICAL PUBLISHING S A ) 61 ( 131 ) 828 - 833 2014年05月 [査読有り]

Background/Aims: We have reported a clinically meaningful local-control effect and a hepatic metastatic tumor-regression effect of transcatheter peripancreatic arterial embolization-hepatic and splenic arterial infusion chemotherapy (TPPAE-HSAIC) for unresectable advanced pancreatic cancer. The aim of this study was to evaluate the clinical significance, of adjuvant surgical resection after TPPAE-HSAIC. Methodology: We assessed histopathological findings and outcomes of 6 patients who underwent surgical resection of tumors judged to be radically resectable after attaining tumor down-staging or long-term tumor control following TPPAE-HSAIC for pancreatic cancer initially diagnosed as unresectable. Results: Clinical stage at the initial diagnosis was T4N0M0 Stage III in 4 patients and T4N0M1 Stage IV in 2 patients. The durations of TPPAE-HSAIC ranged from 5 to 46 months with a median of 19 months. An R0 resection was performed in 5 of the 6 patients (83%) and pathological down-staging, from the viewpoint of clinical stage, was observed in 4 patients. Of the 5 patients with R0 resection, one died from a postoperative complication at 7 months and another from pulmonary metastasis at 30 months post-operatively, while the other 3 patients have survived for 45 to 83 months to date. Conclusions: If surgical resection of pancreatic cancer initially diagnosed as unresectable can be carried out in patients responding favorably to TPPAE-HSAIC, the likelihood of long-term survival might be increased.

DOI PubMed

アデホビル長期投与中にFanconi症候群による低リン血性骨軟化症を発症したB型慢性肝炎の1例

石川和真, 宮西浩嗣, 保木寿文, 田村文人, 河野豊, 高田弘一, 田中信悟, 櫻田晃, 佐藤康史, 佐藤勉, 林毅, 瀧本理修, 小船雅義, 加藤淳二

肝臓 ( (一社)日本肝臓学会 ) 55 ( 3 ) 162 - 169 2014年03月

症例は54歳の男性。2001年より、B型慢性肝炎に対してラミブジンによる治療を受けていたが、経過中にAST、ALTの上昇、HBV DNAの上昇を認められ、2004年よりアデホビルの併用が開始された。2012年7月より両胸郭・股関節痛を自覚したため前医を受診。採血にてALP高値と腎機能障害を認め、徐々に増悪したため精査加療目的に当科紹介となった。精査の結果、近位尿細管障害および腎性低リン血症を認め、骨シンチグラフィでは疼痛部位に一致したテクネシウムの異常集積を認めた。以上よりFanconi症候群および低リン血症性骨軟化症と診断し、原因としてアデホビルが疑われたため、同薬を中止しエンテカビルへ変更したところ、徐々に腎機能障害、骨痛の改善を認めた。アデホビルによるFanconi症候群は少数ながらも近年報告されている。しかし、治療から改善までの詳細な経過を示したものは無いので、本例の経過を報告する。(著者抄録)

DOI

Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma.

Shingo Tanaka, Koji Miyanishi, Masayoshi Kobune, Yutaka Kawano, Toshifumi Hoki, Tomohiro Kubo, Tsuyoshi Hayashi, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Junji Kato

Journal of gastroenterology 48 ( 11 ) 1249 - 58 2013年11月 [査読有り] [国内誌]

BACKGROUND: The rate of onset of hepatocellular carcinoma (HCC) in patients with nonalcoholic steatohepatitis (NASH) has been reported recently to be comparable to that of patients with chronic hepatitis C. However, the precise mechanism contributing to carcinogenesis in the former remains unclear. Although increased oxidative stress is presumed to play a role in carcinogenesis in patients with NASH, this relationship remains to be directly proven. In this study, we investigated the involvement of oxidative DNA damage in hepatocarcinogenesis in patients with NASH. METHODS: Patients with nonalcoholic fatty liver disease who were treated at our university hospital were eligible for enrolment in the study(n = 49). The study cohort included 30 patients with NASH without HCC (NASH without HCC), six HCC patients with NASH (NASH-HCC), and 13 patients with simple steatosis. Quantitative immunohistochemistry with a KS-400 image analyzing system was used for 8-hydroxy-2'-deoxyguanosine (8-OHdG) detection. RESULTS: The 8-OHdG content in the liver tissue of NASH-HCC patients was significantly different from that in the other patients. The median immunostaining intensity was 8.605 in the NASH-HCC cases, which was significantly higher than that in the cases of NASH without HCC (4.845; P = 0.003). Multivariate analysis using hepatic 8-OHdG content as a factor in addition to age and fasting blood sugar revealed a significant difference in clinicopathological factors between NASH-HCC and NASH without HCC cases. Old age (P = 0.015) and high relative immunostaining intensity for intrahepatic 8-OHdG (P = 0.037) were identified as independent factors. CONCLUSIONS: 8-OHdG content in liver tissue may serve a marker of oxidative stress and could be a particularly useful predictor of hepatocarcinogenesis.

DOI PubMed

Safety and effectiveness of low-dose lenalidomide therapy for multiple myeloma complicated with bortezomib-associated interstitial pneumonia.

Nagamachi Y, Yamauchi N, Muramatsu H, Okamoto T, Inomata H, Nozawa E, Koyama R, Ihara K, Nishisato T, Yamada H, Yano T, Tanaka S, Ono K, Kikuchi S, Kato J

[Rinsho ketsueki] The Japanese journal of clinical hematology ( The Japanese Society of Hematology ) 54 ( 5 ) 451 - 456 2013年05月 [査読有り]

症例は，78歳女性。平成22年8月，近医で多発性骨髄腫(IgGκ type, stageIIIA, ISS III)と診断され，デキサメサゾン大量療法をするも効果無く，ボルテゾミブで2コース治療をされた。転居に伴い，同年11月当院入院。骨髄検査で形質細胞29.6%, IgG 5,539 mg/dlであった。入院時，両背部痛，軽度呼吸苦あり，胸部CTで，間質性肺炎と診断した。ステロイド投与で速やかに軽快したが，ボルテゾミブの関与を否定できなかったことから，レナリドミドによる治療を選択した。レナリドミド15 mgを2コース投与したが，間質性肺炎の再燃は認めなかった。又，形質細胞は0.4%, IgG 1,616 mg/dlと低下し，PRであった。白血球減少を認め，GCSFの投与を必要としたが，治療継続中であり，経過は良好である。レナリドミドの本邦PMS（中間報告）では，1,177例中，間質性肺疾患が3例報告されている。その投与量は，2例で25 mg, 1例で10 mgであった。転帰は1例が死亡，1例は未回復，1例は不明で，本症例においては，レナリドミドの投与量を，骨髄抑制後の再開投与量である15 mgとした。ボルテゾミブによる間質性肺炎症例に，レナリドミド投与をする場合，その投与量に関しての規定は無く，本症例は15 mg投与で安全に施行可能であった。文献的考察を含め報告する。

DOI PubMed CiNii

A case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy

Tadashi Doi, Toshinori Okuda, Shinya Minami, Shingo Tanaka, Masahiro Hirakawa, Tomohiro Kubo, Yuki Ikeda, Natsumi Yamauchi, Naoki Uemura, Akihito Fujimi, Yuji Kanisawa

Journal of Japanese Society of Gastroenterology 110 ( 2 ) 248 - 254 2013年02月 [査読有り]

We report a case of anal variceal bleeding successfully treated with endoscopic injection sclerotherapy (EIS). A 64-year-old man with alcoholic liver cirrhosis was hospitalized because of repeated anal bleeding. Colonoscopy revealed external anal varices connecting with rectal varices. Three days after admission, external anal variceal bleeding was observed. Angiography revealed that the anorectal varices formed by hepatofugal inferior mesenteric vein drained into the internal iliac vein. On angiography, the variceal blood flow rate was extremely low, therefore we performed EIS. Seven days after therapy, thrombosis of anorectal varices was observed.

DOI PubMed

A case of ulcerative colitis accompanied with myelodysplastic syndrome successfully treated by cyclosporine

Sho Takahashi, Yasushi Sato, Tamotsu Sagawa, Shingo Tanaka, Kazuyuki Murase, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Ganji Kuroiwa, Michiaki Hirayama, Tetsuro Okamoto, Junji Kato

Journal of Japanese Society of Gastroenterology 108 ( 8 ) 1405 - 1412 2011年08月 [査読有り] [国内誌]

A 64-year-old man had been admitted to a previous hospital because of melena and a diagnosis of ulcerative colitis (UC, pancolitis type) had been made. He had received prednisolone and 5-ASA but steroid-induced hyperamylasemia had developed. Prednisolone had been tapered and halted, but it had resulted in UC relapse and thrombocytopenia. Then, he was referred to our hospital due to severe melena with hypovolemic shock. However, he was also positive for CMV antigen. Thus, we attempted to treat him with ganciclovir for CMV and intravenous cyclosporine (CsA) for UC. According to his clinical course, a reduction of CsA blood concentration induced leukocytopenia. Myelodysplastic syndrome (MDS, RAEB-1) was then revealed after bone marrow biopsy. A high blood CsA concentration may cause the improvement of UC and MDS conditions.

DOI PubMed

Iron chelator deferasirox rescued mice from Fas-induced fulminant hepatitis

Tsutomu Sato, Masayoshi Kobune, Kazuyuki Murase, Yukari Kado, Tetsuro Okamoto, Shingo Tanaka, Shohei Kikuchi, Hiroyuki Nagashima, Yutaka Kawano, Kohichi Takada, Satoshi Iyama, Koji Miyanishi, Yasushi Sato, Rishu Takimoto, Junji Kato

HEPATOLOGY RESEARCH ( WILEY-BLACKWELL ) 41 ( 7 ) 660 - 667 2011年07月 [査読有り] [国際誌]

Aim: Fulminant hepatitis is a disease characterized by development of hepatic failure due to severe liver cell injury. Orthotopic liver transplantation is the therapy proven to improve patient survival; however, less burdensome and safer strategies are required. In a previous study, we showed that iron was intimately involved in hepatocyte apoptosis by demonstrating that spontaneous development of fulminant hepatitis in Long-Evans cinnamon rats was prevented by feeding an iron-deficient diet. Recently, a new iron chelator, deferasirox, has become widely available for the treatment of transfusional hemosiderosis. Deferasirox demonstrated good efficacy and improved compliance due to convenient, once-daily p.o. administration. Our aim was to investigate the efficacy of deferasirox as a therapeutic drug against fulminant hepatitis. Methods: Human primary hepatocytes undergoing Fas-stimulated apoptosis were challenged with deferoxamine (DFO) in vitro. In further in vivo experiments, we tested DFO in a mice model of fulminant hepatitis induced by Fas-stimulation. Results: The apoptosis-inducing activity of anti-Fas antibody on human primary hepatocytes was inhibited by the chelation of iron with DFO. DFO suppressed the Fas-induced production of reactive oxygen species (ROS) and the activation of caspase-3, both of which were also suppressed by antioxidant, N-acetyl-L-cystein. In the in vivo experiments, deferasirox effectively reduced hepatic iron concentrations and rescued mice from Fas-induced fulminant hepatitis. Conclusion: These findings indicated that the iron chelation exerted a hepatoprotective effect by scavenging ROS upstream of caspase-3 and that iron chelation with deferasirox is a potential treatment for patients with fulminant hepatitis.

DOI PubMed

女性は女性医師による大腸内視鏡検査を望んでいるか

大浦佳永, 黒瀬加奈, 牧野聖子, 住吉徹哉, 田中信悟, 田村文人, 對馬隆浩, 水島健, 千葉大樹, 辻靖, 由崎直人, 近藤仁

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 52 ( 12 ) 3347 - 3352 2010年12月

大腸内視鏡検査の女性被験者が女性医師を希望するかどうかについて、アンケート調査を実施した。対象は連続110名(平均年齢53.6歳)で、アンケート調査は検査前後に行った。1)検査前、56%が女性医師による検査を希望していた。特に50歳未満の若年者や検査未経験者は有意に高率に女性医師を希望していた。また、就業女性や無症状スクリーニング被験者も女性医師を希望する傾向が強かった。2)検査後も女性医師を希望する傾向は変わらず、検査前に女性医師を希望した被験者の90%、どちらでもよいと回答していた73%が、次回検査は女性内視鏡医を希望していた。3)女性内視鏡医の育成が必要であるとともに、男性内視鏡医も技術面だけでなく、被験者に対する心遣いや安心感の提供等、精神面の配慮も心がけることが重要と考えられた。

Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer

Yasushi Sato, Tetsuji Takayama, Tamotsu Sagawa, Yasuo Takahashi, Hiroyuki Ohnuma, Syunichi Okubo, Naoaki Shintani, Shingo Tanaka, Masaya Kida, Yasuhiro Sato, Hidetoshi Ohta, Koji Miyanishi, Tsutomu Sato, Rishu Takimoto, Masayoshi Kobune, Koji Yamaguchi, Koichi Hirata, Yoshiro Niitsu, Junji Kato

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 66 ( 4 ) 721 - 728 2010年09月 [査読有り] [国際誌]

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer. Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3 weeks. Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed. DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.

DOI PubMed

脂肪性肝疾患の頻度に及ぼすアルコール摂取の影響

土居忠, 田中信悟, 佐藤康裕, 太田英敏, 南伸弥, 藤見章仁, 蟹澤祐司, 田村文人, 平川昌宏, 小野薫

肝臓 ( (一社)日本肝臓学会 ) 51 ( 9 ) 501 - 507 2010年

脂肪性肝疾患(FLD)の発生に及ぼすアルコール摂取の影響には不明な点が残されている。今回我々は2008年1月から12月までに腹部超音波検査を含む健康診断を受診した3185名を対象に脂肪肝の頻度に対するアルコール摂取の影響を多重ロジスティック回帰分析により解析した。内臓脂肪性肥満、空腹時高血糖、脂質異常症はいずれも脂肪肝頻度の増加と関連していた。1日アルコール摂取量20g未満(少量飲酒群)、20g以上から40g未満(軽度飲酒群)および40g以上から60g未満(中等度飲酒群)では脂肪肝のオッズ比は有意に低下した。男女別に飲酒の影響を検討したところ、男性では軽度飲酒群から中等度飲酒群におけるFLDの調整オッズ比は非飲酒群および1日アルコール摂取量60g以上の多量飲酒群より低かった。一方、女性ではアルコール摂取の影響は明らかでなかった。以上の結果からFLDに及ぼす飲酒の影響には性差があり、男性では軽度ないし中等度までのアルコール摂取は過栄養性FLDの発生を抑制する可能性が示唆された。(著者抄録)

DOI

Adenocarcinoma of Meckel's diverticulum diagnosed by capsule endoscopy and single-balloon enteroscopy

Yasuhiro Sato, Shingo Tanaka, Yutaku Ko, Toshinori Okuda, Fumito Tamura, Akihito Fujimi, Tadashi Doi, Yuji Kanisawa, Hidetoshi Ohta

Clinical Journal of Gastroenterology 2 ( 6 ) 388 - 393 2009年12月 [査読有り] [国内誌]

A case of adenocarcinoma arising in Meckel's diverticulum in a 58-year-old man is reported. Abdominal computed tomography and ultrasonography showed a solid tumor in the middle of abdomen. Capsule endoscopy (CE) showed tumorous lesion in the distal ileum. Single-balloon enteroscopy (SBE) subsequently showed the tumor in Meckel's diverticulum. Furthermore, biopsy specimen obtained from the lesion revealed it as adenocarcinoma. At laparotomy, we found the tumor at the blind end of the diverticulum and enlarged lymph node about 7 cm in diameter in the small intestinal mesentery. Segmental resection of the ileum, including the tumor-bearing diverticulum, was performed along with regional lymph node dissection. Histologically, origin of the tumor was assumed to be ectopic gastric mucosa. Although neoplasm in Meckel's diverticulum is difficult to diagnose preoperatively, the combination of CE and SBE was useful. Based on our search, this is thought to be the first case of neoplasm in Meckel's diverticulum diagnosed endoscopically. © 2009 Springer.

DOI PubMed

A case of early esophageal adenocarcinoma arising from esophageal cardiac glands

Yutaku Ko, Yasuhiro Sato, Shingo Tanaka, Toshinori Okuda, Akihito Fujimi, Tadashi Doi, Yuji Kanisawa, Kazuhiro Iwai, Hidetoshi Ohta

Journal of Japanese Society of Gastroenterology 106 ( 9 ) 1327 - 1333 2009年09月 [査読有り]

A 54-year-old man was referred to our hospital with an esophageal lesion. On esophagogastroduodenoscopy a pedunculated elevated lesion about 15mm in diameter was identified in the abdominal esophagus. The surface of the lesion had irregular nodules with white coating. We found no Barrett's mucosa around the lesion. A biopsy specimen of this tumor showed well-differentiated adenocarcinoma. A lower esophagus-proximal gastrectomy was performed because this tumor was suspected to invade the submucosal layer. Eventually, the histological diagnosis after resection was esophageal adenocarcinoma arising from cardiac glands, limited to the mucosal layer (M2). This origin of the esophageal adenocarcinoma is rare. Furthermore, this form of the tumor is especially unusual, and there have been few reports of similar cases.

DOI PubMed

[Spontaneous pneumothorax, an unusual manifestation of imatinib-resistant chronic eosinophilic leukemia: an autopsy study].

Fujimi A, Kanisawa Y, Tanaka S, Okuda T, Sato Y, Doi T, Ohta H, Iwasaki S, Ishizu A, Huang Y

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine ( The Japanese Society of Internal Medicine ) 98 ( 4 ) 862 - 865 2009年04月 [査読有り]

近年，FIP1L1/PDGFRα融合遺伝子（FP遺伝子）陽性の慢性好酸球性白血病（chronic eosinophilic leukemia；CEL）に対するimatinib（IM）の有効性が示され，治療成績は著しく改善しているが長期予後には不明な点も多い．今回，我々はIMに耐性化し終末期に自然気胸を併発したCEL症例を経験した．剖検で好酸球の肺胞への高度の浸潤およびその近傍の線維化，気腫化が確認され，CELの進行が肺実質の破壊をきたし気胸の原因となったと推定された．

DOI PubMed CiNii

ダブルバルーン小腸内視鏡にて除去しえた小腸内異物の3例

佐川保, 高山哲治, 佐藤康史, 高橋祥, 田中信悟, 小笹里砂, 井山諭, 黒田裕行, 加藤淳二, 新津洋司郎

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 50 ( 10 ) 2684 - 2690 2008年10月

症例1(60歳男性)。日曜大工で釘を誤飲し受診となった。X線では胃内に釘が確認され、内視鏡で摘出を試みたが、釘は胃内になく空腸以降に移動しており、経口的ダブルバルーン小腸内視鏡(DBE)で下部空腸に釘を認め、回収した。症例2(35歳男性)。10年前に過敏性腸症候群の診断を受け、4年前より腸閉塞症状を繰り返し、前医で慢性特発性偽性腸閉塞(CIIP)と診断された。腸管内圧減圧目的に胃瘻の造設、イレウス管の留置がされたものの、今回、イレウス管が断裂し内視鏡での摘出が困難なため、著者らの施設へ紹介受診となった。X線およびCTでは小腸内に断裂したイレウス管が認められ、経口的DBEにて下部空腸内のイレウス管を回収した。症例3(78歳女性)。11年前に回腸狭窄による腸閉塞で回腸部分切除術が行われ、数年前より腹部膨満感が続いていた。著者らの施設へ紹介受診となり、内視鏡ならびにガストログラフィン造影を行なったところ回腸に7cmの狭窄が認められた。更にこの狭窄部を経口的DBEで調べたところPTPが見つかり、これを回収ネットにて回収した。

DOI

[Two cases of advanced gastric cancer in which paclitaxel proved effective after resistance to docetaxel].

Tsushima T, Tsuji Y, Abe S, Tanaka S, Tamura F, Mizushima T, Makino K, Oura K, Honda K, Sumiyoshi T, Yoshizaki N, Kondo H

Gan to kagaku ryoho. Cancer & chemotherapy 34 ( 10 ) 1647 - 1650 2007年10月 [査読有り] [国内誌]

Docetaxel and paclitaxel are demonstrated to be effective for use as salvage therapy for advanced gastric cancer. Both drugs are taxane derivatives but there is only partial cross-resistance between them. For breast cancer and ovarian cancer, there have been several reports that showed docetaxel is effective for paclitaxel-resistant cancer, and vice versa. We experienced two cases of advanced gastric cancer effectively treated by sequential therapy of docetaxel and paclitaxel. One patient was a 43-year-old woman with a type 4 gastric carcinoma, and the other a 51-year-old woman who had suffered a recurrence of the gastric cancer after a total gastrectomy. At first, chemotherapy failed, so we chose docetaxel/high-dose 5-FU (HDFU) for the second-line therapy. After resistance to Docetaxel/HDFU, paclitaxel was effective for third-line treatment of both patients.

PubMed

[Feasibility of modified FOLFIRI regimen for patients with refractory advanced or recurrent colorectal cancer].

Takahari D, Tsuji Y, Tanaka S, Tsushima T, Ohura K, Honda K, Sumiyoshi T, Yoshizaki N, Kondo H

Gan to kagaku ryoho. Cancer & chemotherapy 34 ( 2 ) 207 - 211 2007年02月 [査読有り]

PubMed

[Gastric relapse of stage I ocular adnexal mucosa-associated lymphoid tissue lymphoma].

Sato T, Takimoto R, Iyama S, Ono K, Tanaka S, Araki N, Nishiie K, Murase K, Sato Y, Kobune M, Matsunaga T, Kato J, Niitsu Y

[Rinsho ketsueki] The Japanese journal of clinical hematology ( 一般社団法人日本血液学会 ) 48 ( 1 ) 56 - 60 2007年01月 [査読有り] [国内誌]

症例は57歳，男性。右涙腺に原発するmucosa-associated lymphoid tissue lymphoma (MALT lymphoma)に対し，局所への放射線照射が施行された。その際の胃内視鏡検査では胃粘膜に軽度の炎症性変化が指摘され，ウレアーゼテストが陽性であったため，ピロリ菌の除菌療法が施行された。その2年後，再び胃内視鏡検査を施行したところ，MALTリンパ腫病変が検出された。涙腺病変と胃病変のIgH遺伝子をサザン法で検索したところ，全く同一の再構成パターンが得られた。このため，ピロリ菌感染による慢性炎症を母地とした異所性発癌ではなく，原発巣の胃転移と考えた。また，涙腺MALTリンパ腫のリンパ腫細胞は，リンパ球が消化管粘膜へ接着する際に必須であるintegrin α4β7を高発現していたため，この接着分子が胃転移に重要な働きをした可能性があると考えられた。

DOI PubMed CiNii

[Present status of home therapy cancer patients using an infusor].

Tsuji Y, Tsushima T, Tanaka S, Mizushima T, Tamura F, Chiba H, Honda K, Makino K, Ohura K, Sumiyoshi T, Yoshizaki N, Kondo H

Gan to kagaku ryoho. Cancer & chemotherapy 33 Suppl 2 260 - 263 2006年12月 [査読有り] [国内誌]

We started a department of medical oncology and the risk management system of cancer chemotherapy since April in 2004. After that, chemotherapy administration increased steadily in numbers, especially on an outpatient basis. For reliable venous access, we made active use of a central venous Port (more than 60% of cases) as a rout of administration. Fifty five patients with advanced colorectal cancer were treated by FOLFIRI or FOLFOX regimen from April 2005 to June 2006. Two hundred sixty four cycles of FOLFIRI and 276 cycles of FOLFOX were administered. One hundred sixteen cycles (44%) and 117 cycles (42%) were performed through home therapy, respectively. Twenty five out of 55 patients could shift to home therapy using an infusor. Nine out of 30 patients wanted to continue on an inpatient basis, because their private insurance for medical care did not support the outpatient chemotherapy.

PubMed

[Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells].

Matsunaga T, Sato T, Iyama S, Tanaka S, Murase K, Sato Y, Kobune M, Takimoto R, Kato J, Kuroda H, Niitsu Y

[Rinsho ketsueki] The Japanese journal of clinical hematology ( The Japanese Society of Hematology ) 47 ( 11 ) 1457 - 1462 2006年11月 [査読有り] [国内誌]

症例は72歳, 男性。頸部リンパ節腫脹の精査を目的に入院し, リンパ節生検の結果から, 末梢性T細胞性リンパ腫 (peripheral T cell lymphoma; PTCL) と診断した。著明な好酸球増多を認めたため, 血清Interleukin-5 (IL-5) を測定したところ高値を示した。また, 生検したリンパ節組織の免疫染色ではIL-5陽性の細胞が散見された。CHOP療法を2クール施行したところ, 腫大したリンパ節は消失し, 好酸球数は正常となった。また, これにともない血清IL-5も正常化した。PTCLでは稀に好酸球増多を合併すると報告されているが, 本症例では腫瘍細胞由来のIL-5が原因と推測された。

DOI PubMed CiNii

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