Details of a Researcher - Kanai, Takanori

Papers - Kanai, Takanori

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Second-look endoscopy after endoscopic submucosal dissection for gastric neoplasms

Nishizawa Toshihiro, Suzuki Hidekazu, Kinoshita Satoshi, Goto Osamu, Kanai Takanori, Yahagi Naohisa

Digestive Endoscopy 27 ( 3 ) 279 - 284 2015.03

ISSN 0915-5635

Routine second-look endoscopy after gastric endoscopic submucosal dissection (ESD) remains controversial. The aim of the present study was to systematically evaluate the efficacy of second-look endoscopy for gastric ESD. PubMed, the Cochrane library, and the Igaku-chuo-zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data were combined to calculate a pooled odds ratio (OR) for developing post-ESD bleeding. The database search yielded three randomized trials (854 patients). Compared with second-look endoscopy, the pooled OR for post-ESD bleeding without second-look endoscopy was 0.69 (95% confidence interval [CI]: 0.38-1.26, P = 0.228), without significant heterogeneity. There were no significant differences between second-look endoscopy and no second-look endoscopy with regard to large tumor size (>20 mm). This systematic review and meta-analysis showed that second-look endoscopy had no advantage for the prevention of post-ESD bleeding in patients without a high risk of bleeding.

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Pregnant woman with non-comatose autoimmune acute liver failure in the second trimester rescued using medical therapy

Sato Hirokazu, Tomita Kengo, Yasue Chihiro, Umeda Rumiko, Ebinuma Hirotoshi, Ogata Sho, Du Wenlin, Soga Shigeyoshi, Maruta Koji, Yasutake Yuichi, Narimatsu Kazuyuki, Usui Shingo, Watanabe Chikako, Komoto Shunsuke, Teratani Toshiaki, Suzuki Takahiro, Yokoyama Hirokazu, Saito Hidetsugu, Nagao Shigeaki, Hibi Toshifumi, Miura Soichiro, Kanai Takanori, Hokari Ryota

Hepatology Research 45 ( 3 ) 349 - 355 2015.03

ISSN 1386-6346

We present the case of a 25-year-old woman at 16 weeks of gestation who presented with non-comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine doses (50mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non-comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.

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Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer

Nishizawa Toshihiro, Suzuki Hidekazu, Kanai Takanori, Yahagi Naohisa

Journal of Clinical Biochemistry and Nutrition 56 ( 2 ) 85 - 90 2015.03

ISSN 0912-0009

Mucosal protective agents may improve healing of patients with endoscopic submucosal dissection-induced ulcers. The present study systematically evaluated published clinical trials to determine whether combined therapeutic use of mucosal protective agents and proton pump inhibitors can improve the outcome of patients with endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitors alone. PubMed, the Cochrane Library, and the Igaku-Chuo-Zasshi database were searched to identify eligible randomized trials for systematic review. We identified 11 randomized trials for inclusion in our study (1,160 patients). Pooled endoscopic submucosal dissection-induced ulcer healing rates were 45.8% and 34.4% for patients with or without mucosal protective agents, respectively. The odds ratio was 2.28 (95% confidence interval, 1.57-3.31) with no significant study heterogeneity. In conclusion, the systematic review and meta-analysis showed that the combined therapeutic use of proton pump inhibitors and mucosal protective agents improved healing rates of endoscopic submucosal dissection-induced ulcers compared to treatment with proton pump inhibitor monotherapy.

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栄養指導によるアルコール性肝障害の進展予防の提案

KANAI Takanori

アルコールと医学生物学 33 27 - 31 2015.03

Research paper (scientific journal), Joint Work

栄養指導によるアルコール性肝障害(ALD)の進展予防について検討した。ALDを住民検診や定期健診で指摘された男性48例を対象とした。栄養相談を拒否した群29例は、受けた群19例より比較的若年で、BMIが高く、独身や単身赴任が多く、多忙や自分で節酒できるなど依存症の否認に近い理由で拒否する例が多かった。ALTは拒否群で高く、γGTPは受講群で高かった。管理栄養士による栄養相談を受けたALD群で、肝機能ならびにTGの改善率が高かった。中等度飲酒群、非アルコール性脂肪性肝障害(NAFLD群)における栄養相談を受けていない群では、肝機能、TGの改善はほとんどみられなかった。栄養相談を受けた中等度飲酒例群ではAST、ALT、γ-GTPとも改善を認め、非アルコール性脂肪性肝障害群ではALTのみ改善を認めたが、改善の程度はALD群より少なかった。TGの改善もALD群で最も顕著であった。

【腸内細菌と健康・疾患との関わり】腸内細菌に関する最近の知見

KANAI Takanori

機能性食品と薬理栄養 8 ( 6 ) 500-504 2015.02

Joint Work, ISSN 1348-2564

Dysbiosisと糞便移植治療、その臨床応用について

KANAI Takanori

臨床栄養 126 ( 2 ) 124 - 125 2015.02

ISSN 0485-1412

【炎症性腸疾患-病態研究から標的治療への展開-】病態研究から標的治療へ　炎症性腸疾患における腸内細菌の病態への関与と標的治療への応用

KANAI Takanori

最新医学 70 ( 2 ) 222-228 2015.02

Joint Work, ISSN 0370-8241

炎症性腸疾患の原因はいまだ不明な点が多いが,遺伝学的因子,環境因子,免疫学的な因子などの複合的な因子が関与していると考えられている.特に腸内細菌との関係については,腸内細菌叢解析の進歩によりプロバイオティクスを中心とした腸内細菌をターゲットとした治療法が注目されてきている.Bacteroides fragilis,Clostridium butyricum,Fusicatenibacter saccharivoransなどの腸内細菌は,IL-10を介して腸炎抑制効果を有することより,治療応用や疾患活動性評価に有用である可能性が期待されている.(著者抄録)

Dexmedetomidine versus midazolam for gastrointestinal endoscopy

Nishizawa Toshihiro, Suzuki Hidekazu, Sagara Seiji, Kanai Takanori, Yahagi Naohisa

Digestive Endoscopy 27 ( 1 ) 8 - 15 2015.01

ISSN 0915-5635

Background and Aim Patients who undergo gastrointestinal endoscopy often require sedatives such as midazolam and the more recently developed alpha-2 agonist, dexmedetomidine. To assess the efficacy and safety of dexmedetomidine sedation for gastrointestinal endoscopy, we conducted a systematic review and meta-analysis of randomized controlled trials comparing dexmedetomidine with midazolam. Methods We searched PubMed, the Cochrane library, and the Igaku-chuo-zasshi database in order to identify randomized trials eligible for inclusion in our meta-analysis. Data from the eligible studies were combined to calculate pooled odds ratios (OR) or weighted mean differences (WMD). Results We identified nine randomized trials from the database search. Compared to that of midazolam, the pooled OR for restlessness of dexmedetomidine was 0.078 (95% confidence interval [CI]: 0.013-0.453, P < 0.0001), and there was no significant heterogeneity among the trial results. Dexmedetomidine significantly increased Ramsay sedation score compared with midazolam (WMD: 0.401, 95% CI: 0.110-0.692, P = 0.0069), without significant heterogeneity. Compared with midazolam, the pooled OR for hypoxia, hypotension, and bradycardia with dexmedetomidine sedation were 0.454 (95% CI: 0.098-2.11), 1.370 (95% CI: 0.516-3.637), and 2.575 (95% CI: 0.978-6.785), respectively, with no significant differences detected between the groups. Conclusion This meta-analysis shows that dexmedetomidine is a safe and effective sedative agent for gastrointestinal endoscopy, especially endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection.

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間接ビリルビン優位の体質性黄疸合併慢性C型肝炎に対し、ペグインターフェロン+リバビリン+シメプレビル3剤併用療法を施行し、黄疸の増強後に回復を認めた1例

KANAI Takanori

肝臓 56 ( 1 ) 13 - 17 2015.01

Joint Work, ISSN 0451-4203

症例は42歳、男性。HCV抗体陽性を指摘され当院紹介された。体質性黄疸を指摘されていたが、肝機能異常を認めたことはなかった。一般血液検査ではTB、ALT以外に異常は認めなかった。HCVは1型でウイルス量7.1Log IU/mLのため、ペグインターフェロン+リバビリン+シメプレビル3剤併用療法を開始した。投与前血清総ビリルビン値(TB)2.5mg/dl、直接ビリルビン値(DB)0.1mg/dLであったが、3週目にTB 8.1mg/dLと上昇した。肝機能は正常化しているため薬剤は減量せず継続し、4週目にはTBも5.1mg/dLと低下し、HCV-RNAも陰性化した。24週目はTB 2.7mg/dlと投与前値に回復した。3剤併用療法では、一過性のTB上昇が報告されている。体質性黄疸合併慢性C型肝炎に対し3剤併用療法を施行し、黄疸の増強後に回復を認めた症例を経験したので報告した。間接ビリルビン優位の体質性黄疸合併慢性C型肝炎症例でも3剤併用後のTBの上昇は一過性で禁忌ではなく、DBや肝逸脱酵素の上昇などを伴わない限り中止の必要性はないと考えられた。(著者抄録)

Risk Factors for Decreased Bone Mineral Density in Japanese Patients with Inflammatory Bowel Disease: A Cross-Sectional Study.

KANAI Takanori

Clin Nutr. 34(6):1202-9. 2015

Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids

Matano Mami, Date Shoichi, Shimokawa Mariko, Takano Ai, Fujii Masayuki, Ohta Yuki, Watanabe Toshiaki, Kanai Takanori, Sato Toshiro

Nature Medicine 21 ( 3 ) 256 - 262 2015

ISSN 1078-8956

Human colorectal tumors bear recurrent mutations in genes encoding proteins operative in the WNT, MAPK, TGF-β, TP53 and PI3K pathways. Although these pathways influence intestinal stem cell niche signaling, the extent to which mutations in these pathways contribute to human colorectal carcinogenesis remains unclear. Here we use the CRISPR-Cas9 genome-editing system to introduce multiple such mutations into organoids derived from normal human intestinal epithelium. By modulating the culture conditions to mimic that of the intestinal niche, we selected isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, and in the oncogenes KRAS and/or PIK3CA. Organoids engineered to express all five mutations grew independently of niche factors in vitro, and they formed tumors after implantation under the kidney subcapsule in mice. Although they formed micrometastases containing dormant tumor-initiating cells after injection into the spleen of mice, they failed to colonize in the liver. In contrast, engineered organoids derived from chromosome-instable human adenomas formed macrometastatic colonies. These results suggest that 'driver' pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior.

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Recent trends in diagnostic techniques for inflammatory bowel disease

Naganuma Makoto, Hosoe Naoki, Kanai Takanori, Ogata Haruhiko

Korean Journal of Internal Medicine 30 ( 3 ) 271 - 278 2015

ISSN 1226-3303

Although ileocolonoscopy is the gold standard for diagnosis of inflammatory bowel disease and is useful for assessing the disease severity in the colon and terminal ileum, several alternative diagnostic techniques have been developed recently. For ulcerative colitis (UC), magnification colonoscopy, endocytoscopy, and confocal laser endomicroscopy enable assessment of histological inflammation without the need for biopsy. Capsule endoscopy is useful for detection of small intestinal and colonic lesions in both female and male patients. For UC, capsule endoscopy may be useful for evaluating colonic inflammation in patients with a previous poor colonoscopy experience, while it should be used only in Crohn’s disease (CD) patients with unexplained symptoms when other examinations are negative. Magnetic resonance enterography (MRE) is particularly useful for detecting transmural inflammation, stenosis, and extraintestinal lesions, including abscesses and fistulas. MRE is also useful when evaluating small and large intestinal lesions, even in cases with severe strictures in which full evaluation of the small bowel would be virtually impossible using other devices. Therefore, the appropriate diagnostic devices for detecting CD lesions in the small and large intestine should be used.

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A case of type C chronic hepatitis with constitutional hyperbilirubinemia treated by peginterferon-alpha + ribavirin + simeprevir

Horie Yoshinori, Ebinuma Hirotoshi, Nakamoto Nobuhiro, Kanai Takanori

Acta Hepatologica Japonica 56 ( 1 ) 13 - 17 2015

ISSN 0451-4203

We reported a case of a 42-y/o man with constitutional hyperbilirubinemia and type C chronic hepatitis treated by peginterferon-alpha + ribavirin + simeprevir. His serum TB level was increased (from 2.5 to 8.1 mg/ dL 3 w after treatment), but gradually decreased thereafter (5.1 mg/dL 4 w after treatment), and recovered (3.0 mg/dL) 4 w after stopping simeprevir. HCV-RNA has been negative and liver function has been normal after treatment. He did not have either any symptom or abnormality in laboratory data except TB level during the treatment. Simeprevir was reported to sometimes increase serum TB level. In this case, organic anion- transporting polypeptide 1B1 (OATP1B1) seems to be inhibited by simeprevir, because the increase in indirect bilirubin was dominant. This case suggests that the treatment for type C chronic hepatitis with simeprevir is possible even in patients with constitutional hyperbilirubinemia, because the increase in serum TB level was temporal and recovered after stopping simeprevir.

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The gut microbiota and inflammatory bowel disease

Matsuoka Katsuyoshi, Kanai Takanori

Seminars in Immunopathology 37 ( 1 ) 47 - 55 2015

ISSN 1863-2297

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut. Although the precise cause of IBD remains unknown, the most accepted hypothesis of IBD pathogenesis to date is that an aberrant immune response against the gut microbiota is triggered by environmental factors in a genetically susceptible host. The advancement of next-generation sequencing technology has enabled identification of various alterations of the gut microbiota composition in IBD. While some results related to dysbiosis in IBD are different between studies owing to variations of sample type, method of investigation, patient profiles, and medication, the most consistent observation in IBD is reduced bacterial diversity, a decrease of Firmicutes, and an increase of Proteobacteria. It has not yet been established how dysbiosis contributes to intestinal inflammation. Many of the known IBD susceptibility genes are associated with recognition and processing of bacteria, which is consistent with a role of the gut microbiota in the pathogenesis of IBD. A number of trials have shown that therapies correcting dysbiosis, including fecal microbiota transplantation and probiotics, are promising in IBD.

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Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy

Nishizawa Toshihiro, Nishizawa Yuko, Yahagi Naohisa, Kanai Takanori, Takahashi Masahiko, Suzuki Hidekazu

Journal of Gastroenterology and Hepatology (Australia) 29 ( S4 ) 20 - 24 2014.12

ISSN 0815-9319

Background and Aim: Several studies have reported that the application of rebamipide during the eradication of Helicobacter pylori can improve the eradication rate. However, the efficacy and safety are controversial. The present study systematically evaluated whether rebamipide improves the eradication rate of H.pylori by conducting a meta-analysis based on randomized controlled trials (RCTs). Methods: Literature searches were conducted in the following database: PubMed, the Cochrane Library, and the Igaku-chuo-zasshi database in Japan. A meta-analysis of all RCTs comparing rebamipide supplementation with non-rebamipide-containing therapy was performed. Results: We identified six randomized trials (611 patients). Pooled H.pylori eradication rates by per-protocol analysis were 73.3% and 61.4% for patients with or without rebamipide, respectively. The odds ratio was 1.74 (95% confidence interval. 1.19-2.53). Conclusions: Supplementation with rebamipide might be effective in increasing the H.pylori eradication rates of proton-pump inhibitor-amoxicillin dual therapy.

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Mucosal expression of aquaporin-4 in the stomach of histamine type 2 receptor knockout mice and Helicobacter pylori-infected mice

Fukuhara Seiichiro, Matsuzaki Juntaro, Tsugawa Hitoshi, Masaoka Tatsuhiro, Miyoshi Sawako, Mori Hideki, Fukushima Yasushi, Yasui Masato, Kanai Takanori, Suzuki Hidekazu

Journal of Gastroenterology and Hepatology (Australia) 29 ( S4 ) 53 - 59 2014.12

ISSN 0815-9319

Background and Aim: Basolateral water channel, aquaporin-4 (AQP4), is known to be expressed in gastric parietal cells, especially in the basal side of gastric mucosa. However, the role of AQP4 in the stomach is still unknown. Histamine type 2 receptor (H₂R) knockout mice, which are characterized by suppressed gastric acid secretion, are known as formation of mucosal hyperplasia with cystic dilatation and spasmolytic polypeptide-expressing metaplasia (SPEM) in the stomach. The aim of the present study is to investigate whether the expression of AQP4 is changed by the condition of acid suppression and Helicobacter pylori infection. Methods: Male H₂R knockout mice and their controls (C57BL/6) were used. H.pylori was orally infected at the age of 5 weeks. The distributions of AQP4 and H⁺/K⁺-ATPase in the gastric mucosa were investigated by fluorescent immunohistochemistry. The mRNA expressions of AQP4, H⁺/K⁺- ATPase, sonic hedgehog (Shh), and trefoil factor-2 (TFF2) were investigated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Results: In the H₂R knockout mice, the distribution of AQP4-positive parietal cells was extended toward the surface of the fundic glands. Although the mRNA expression levels of AQP4 and H⁺/K⁺ ATPase were elevated in H₂R knockout mice at the age of 20 weeks, the elevations were not maintained by aging or H.pylori infection. In H₂R knockout mice with H.pylori infection, the expression level of TFF2mRNA was elevated while the ratio between AQP4 and H⁺/K⁺ ATPase mRNA expression was decreased compared with the H₂R knockout mice without H.pylori infection. Conclusions: In the H₂R knockout mice, massive SPEM was induced by H.pylori colonization and the ratio between AQP4 and H⁺/K⁺ ATPase mRNA expression was decreased.

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Fecal microbiota transplantation for gastrointestinal diseases

Matsuoka Katsuyoshi, Mizuno Shinta, Hayashi Atsushi, Hisamatsu Tadakazu, Naganuma Makoto, Kanai Takanori

Keio Journal of Medicine 63 ( 4 ) 69 - 74 2014.12

ISSN 0022-9717

Fecal microbiota transplantation (FMT) is a treatment to restore the normal microbial composition of the gut by introducing fecal microbiota obtained from a healthy donor into a diseased individual. There has been a growing interest in the use of FMT as a treatment of various diseases including Clostridium difficile infection (CDI), inflammatory bowel disease, and irritable bowel syndrome. Despite the increasing application of FMT, there are no standard protocols. Many aspects of FMT procedures vary regarding donor selection, preparation of fecal materials, recipient preparation, and route of administration. FMT is most successful in treating recurrent CDI. A randomized controlled trial reported a success rate of approximaetly 90%. Ulcerative colitis (UC) is a potentially good indication for FMT, although limited evidence is available on the use of FMT for the treatment of UC. Only several small case series have been reported, and the results in terms of efficacy are inconsistent. FMT can also be used to treat diseases other than gastrointestinal disorders in which the gut microbiota is disturbed, e.g., cardiovascular diseases, autoimmune diseases, and metabolic disorders. There remain many unanswered questions with regard to FMT, and more research is required in this field.

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Control of tip deflection by right pinkie shaft grip

Nishizawa Toshihiro, Uraoka Toshio, Suzuki Hidekazu, Ochiai Yasutoshi, Goto Osamu, Fujimoto Ai, Maehata Tadateru, Kanai Takanori, Yahagi Naohisa

Gastrointestinal Endoscopy 80 ( 6 ) 1208 2014.12

ISSN 0016-5107

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Control of the treatment device for endoscopy by the left hand

Nishizawa Toshihiro, Uraoka Toshio, Suzuki Hidekazu, Ochiai Yasutoshi, Goto Osamu, Fujimoto Ai, Kanai Takanori, Yahagi Naohisa

Gastrointestinal Endoscopy 80 ( 6 ) 1206 - 1207 2014.12

ISSN 0016-5107

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Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia

Imaeda Hiroyuki, Hosoe Naoki, Kashiwagi Kazuhiro, Ida Yosuke, Nakamura Rieko, Suzuki Hidekazu, Saito Yoshimasa, Yahagi Naohisa, Iwao Yasushi, Kitagawa Yuko, Hibi Toshifumi, Ogata Haruhiko, Kanai Takanori

World Journal of Gastroenterology 20 ( 43 ) 16311 - 16317 2014.11

ISSN 1007-9327

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN).METHODS: Surveillance esophagogastroduodenoscopy (EGD) using a TME was conducted in 182 patients that had undergone ESD for SGN. Autofluorescence imaging (AFI) was conducted after white-light imaging (WLI). When SGN was suspicious, magnifying endoscopy with narrow-band imaging (ME-NBI) was conducted. Final diagnoses were made by histopathologic findings of biopsy specimens. The detection rates of lesions in WLI, AFI, and NBI, and the characteristics of lesions detected by WLI and ones missed by WLI but detected by AFI were examined. The sensitivity, specificity, and accuracy of endoscopic diagnosis using WLI, AFI and ME-NBI were evaluated.RESULTS: In 242 surveillance EGDs, 27 lesions were determined pathologically to be neoplasias. Sixteen early gastric cancers and 6 gastric adenomas could be detected by WLI. Sixteen lesions were reddish and 6 were whitish. Five gastric neoplasias were missed by WLI but were detected by AFI, and all were whitish and protruded gastric adenomas. There was a significant difference in color and pathology between the two groups (P = 0.006). Sensitivity, specificity and accuracy in MENBI were higher than those in both WLI and AFI. Specificity and accuracy in AFI were lower than those in WLI.CONCLUSION: Surveillance using trimodal imaging endoscopy might be useful for detecting another lesion after endoscopic submucosal dissection for superficial gastric neoplasia.

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