Papers - Kanai, Takanori

Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis.

Shinzaki S, Matsuoka K, Iijima H, Mizuno S, Serada S, Fujimoto M, Arai N, Koyama N, Morii E, Watanabe M, Hibi T, Kanai T, Takehara T, Naka T.

J Crohns Colitis 11 ( 1 ) 84 - 91 2017.01

Joint Work, Accepted

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BACKGROUND AND AIMS:

Although several noninvasive and easily accessible biomarkers for inflammatory bowel disease [IBD] are available, their sensitivity and specificity are not adequate to be used as single markers and do not overrule the need for endoscopic evaluation. We previously reported that serum leucine-rich alpha-2 glycoprotein [LRG] was a novel biomarker for rheumatoid arthritis and IBD. We herein investigated whether LRG could indicate endoscopic activity in patients with ulcerative colitis [UC].

METHODS:

Serum LRG concentrations were determined by enzyme-linked immunosorbent assay [ELISA] in consecutive 129 patients with UC in two tertiary care hospitals, and associations of LRG with clinical and endoscopic activities were evaluated. Clinical activity index [CAI] < 6 was defined as clinical remission, and mucosal healing [MH] and complete mucosal healing were defined as Matts' endoscopic grades of 1 or 2 and grade of 1, respectively.

RESULTS:

Serum LRG levels were significantly increased and correlated with clinical and endoscopic activities in patients with UC. LRG levels were associated with both clinical and endoscopic activities even in patients with normal serum C-reactive protein [CRP] levels. Furthermore, LRG levels were significantly lower in patients with complete MH and deep remission. Serial measurements of LRG levels in a subset of patients demonstrated that LRG was significantly elevated during the endoscopically active stage compared with that during the MH stage.

CONCLUSIONS:

Serum LRG is a novel biomarker for detecting MH during disease course in patients with UC and a surrogate marker of endoscopic inflammation in patients with normal CRP levels.


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Successful EUS-guided nondilated pancreatic duct stent placement in patient with refractory pancreatic fistula after pancreaticoduodenectomy.

KANAI Takanori

VideoGIE  2017

The Prognosis of Severe Acute Pancreatitis Varies According to the Segment Presenting With Low Enhanced Pancreatic Parenchyma on Early Contrast-Enhanced Computed Tomography: A Multicenter Cohort Study

KANAI Takanori

Pancreas 46(7):867-873 2017

Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice

KANAI Takanori

Cell Rep 20(7):1513-1524 2017

Benefit of rebiopsy for deciding treatment strategy in rectal cancer: A case report

KANAI Takanori

Oncol Lett (3):3697-3700 2017

Curative resectability of gastrointestinal cancer identified from iron deficiency anemia

KANAI Takanori

Oncol Lett 14(4):4301-4304 2017

Inter-evaluator heterogeneity of clinical diagnosis for locally advanced esophageal squamous cell carcinoma

KANAI Takanori

Esophagus 14(4):324-332 2017

Antibiotic resistance and gyrA mutation affect the efficacy of 10-day sitafloxacin-metronidazole-esomeprazole therapy for Helicobacter pylori in penicillin allergic patients

KANAI Takanori

United European Gastroenterol J 5(6):796-804 2017

Effect of prophylactic clipping in colorectal endoscopic resection: A meta-analysis of randomized controlled studies.

KANAI Takanori

United European Gastroenterol J 5(6):859-867 2017

Changes in the Clinical Features and Long-term Outcomes of Colonic Diverticulitis in Japanese Patients

KANAI Takanori

Intern Med 10.2169/internalmedicine.7710- 2017

Commensal Lactobacillus controls immune tolerance during acute liver injury in mice

KANAI Takanori

Cell Reports 21(5):1215-1226 2017

Detection of bacterial DNA by in situ hybridization in patients with decompensated liver cirrhosis

KANAI Takanori

BMC Gastroenterol  2017

Enteric Glial Dysfunction Evoked by Apolipoprotein E Deficiency Contributes to Delayed Gastric Emptying

KANAI Takanori

Dig Dis Sci 10.1007/s10620-017-4820-7 2017

Clinical and pharmacokinetic factors associated with adalimumab-induced mucosal healing in patients with Crohn's disease

KANAI Takanori

Clin Gastroenterol Hepatol (Clinical Gastroenterology and Hepatology)  S1542-3565(17)31303-4 ( 4 ) 542 - 549.e1 2017

ISSN  15423565

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© 2018 AGA Institute Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

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The role of colorectal endoscopic submucosal dissection in patients with ulcerative colitis.

KANAI Takanori

Gastrointest Endosc (Gastrointestinal Endoscopy)  87 ( 4 ) 1079 - 1084 2017

ISSN  00165107

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© 2018 American Society for Gastrointestinal Endoscopy Background and Aim: Patients with ulcerative colitis have an increased risk of colorectal dysplasia. Endoscopic submucosal dissection (ESD) for neoplastic lesions in ulcerative colitis remains controversial. The aim of this study was to clarify the role of ESD in the treatment strategy for ulcerative colitis. Methods: We retrospectively investigated 25 patients with ulcerative colitis in clinical remission who underwent colorectal ESD at 2 referral centers. We analyzed short-term and long-term outcomes. Preoperative diagnoses based on biopsy or endoscopy were also compared with the histologic diagnoses of resected specimens. Results: The mean size of the resected specimens was 34.9 ± 17.1 mm. The mean procedure time for ESD was 71.3 minutes. En bloc resection and R0 resection rates were achieved in 100% (25/25) and 76% (19/25), respectively. Postoperative bleeding and perforation during the procedure occurred in 0% and 4%, respectively. Five patients with noncurative resection underwent additional surgery. During a median 21 months (range, 8-80 months) follow-up, local recurrence did not occur. Metachronous high-grade dysplasia occurred in 1 case (4%). The biopsy predicted a final histologic diagnosis of carcinoma with a sensitivity of 72.2% (95% confidence interval [CI], 46.5-90.3), accuracy of 78.2% (95% CI, 56.3-92.5). The endoscopic findings predicted a final histologic diagnosis of carcinoma with a sensitivity of 72.2% (95% CI, 46.5-90.3), accuracy of 76% (95% CI, 54.9-90.6). Conclusion: ESD for neoplasms in ulcerative colitis is feasible by expert endoscopists and may avoid unnecessary surgery. Because the biopsy and endoscopic findings had relatively low accuracy for the final histology, ESD could have a curative as well as a diagnostic purpose.

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Endoscopic string clip suturing method: a prospective pilot study (with video)

KANAI Takanori

Gastrointest Endosc (Gastrointestinal Endoscopy)  87 ( 4 ) 1074 - 1078 2017

ISSN  00165107

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© 2018 American Society for Gastrointestinal Endoscopy Background and Aims: We developed a suturing method with string and clips for a single-channel endoscope. The feasibility of the string clip suturing method is evaluated in this prospective pilot study. Methods: This study involved 10 consecutive patients who underwent endoscopic submucosal dissection (ESD) for a duodenal tumor. Polyester string was tied to the arm of a partially out thrust clip. The clip and string can be passed through the instrument channel (3.2 mm) of a single-channel endoscope. The clip with string was placed at the distal edge of the large mucosal defect. A second clip was hooked on the string and placed on the opposite side. Both clips were gathered by pulling the free end of the string, and additional clips were placed to achieve complete closure. This method was compared with that for the previous 10 patients without mucosal closure after duodenal ESD. Results: Mean size of resected specimens was 39.1 ± 12.4 mm. The success rate of the string clip suturing method was 100% (10/10). The mean procedure time was 23.4 ± 13.8 minutes. Perforation during ESD occurred in 1 patient and was successfully closed by this method. None of the treated patients developed serious adverse events after the procedure. Compared with the no-suture group, the length of stay was significantly shorter (P =.038). Conclusion: The string clip suturing method appears to be a safe and effective method for closure of large mucosal defects. (Clinical trial registration number: UMIN000023698.)

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Efficacy of Indigo naturalis in a Multicenter Randomized Controlled Trial of Patients with Ulcerative Colitis.

KANAI Takanori

Gastroenterology (Gastroenterology)  154 ( 4 ) 935 - 947 2017

ISSN  00165085

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© 2018 AGA Institute Background & Aims: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. Methods: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0–1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. Results: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P <.0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P =.0004) and the 2.0 g IN group (38.1%, (P =.0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P =.0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. Conclusions: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5–2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).

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Reply to Gheorghe et al.

KANAI Takanori

Endoscopy  2017

Gut microbiota-mediated generation of saturated fatty acids elicits inflammation in the liver in murine high-fat diet-induced steatohepatitis.

KANAI Takanori

BMC Gastroenterol  2017

The impact of visceral adipose tissue as best predictor for difficult colonoscopy and the clinical utility of a long small-caliber scope as rescue.

KANAI Takanori

PLoS One  2017