研究者詳細 - 田中　信悟

論文 - 田中　信悟

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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)

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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)

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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)

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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。

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