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

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