Takuya Inoue

Bio: Takuya Inoue is an academic researcher from Osaka Medical College. The author has contributed to research in topics: Ulcerative colitis & Cancer. The author has an hindex of 29, co-authored 132 publications receiving 2382 citations. Previous affiliations of Takuya Inoue include Veterans Health Administration & Case Western Reserve University.

Delayed perforation: A hazardous complication of endoscopic resection for non-ampullary duodenal neoplasm

Abstract: Background Perforation is a major complication of endoscopic resection for gastrointestinal neoplasms. However, little is known about delayed perforation after endoscopic resection for non-ampullary duodenal neoplasm. The aim of the present study was to investigate the clinical features of delayed perforation after endoscopic resection for non-ampullary duodenal neoplasm. Patients and Methods This was a retrospective cohort study conducted in a referral cancer center. A total of 63 patients (41 with adenomas and 22 with carcinomas) underwent endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) from January 1993 to December 2011. Incidence, outcome, and factors associated with occurrence of delayed perforation were investigated. Results Delayed perforation occurred in four patients (6.3%). All lesions were located distal to Vater's ampulla. Three of four delayed perforations occurred within 36 h after endoscopic resection. All patients developed retroperitonitis, and two also had retroperitoneal abscesses. Although three patients were cured with conservative management, a long hospital stay was required (28-, 80-, and 81-day hospital stay, respectively). One patient required emergency surgery as a result of panperitonitis. There was, fortunately, no mortality in this series. The significant predictors of delayed perforation were location (distal to Vater's ampulla, P = 0.007) and resection method (ESD and piecemeal EMR, P = 0.003). Conclusion Endoscopic resection for non-ampullary duodenal neoplasms has a possible risk of morbid complication i.e. delayed perforation, especially in patients with lesions located on the side distal from the ampulla and who are treated with piecemeal EMR or ESD.

Comparative study of conventional colonoscopy and pan-colonic narrow-band imaging system in the detection of neoplastic colonic polyps: a randomized, controlled trial.

Abstract: Background. Detection and removal of adenomas by colonoscopy is an important means for preventing cancer; however, small adenomas may be missed during colonoscopy. The narrow-band imaging (NBI) system clearly enhances the microvasculature in neoplastic lesions, making it appear as a dark complex. Therefore, the NBI system may improve the detection of colonic neoplasias. However, no randomized, controlled trials have evaluated the efficacy of a pan-colonic NBI system in adenoma detection. We conducted a randomized, controlled trial to determine the efficacy of the pancolonic NBI system in adenoma detection. Methods. Two hundred forty-three patients were randomized, 121 to conventional colonoscopy and 122 to pan-colonic NBI system. Demographics, indication for colonoscopy, and quality of preparation were similar between groups. Results. Extubation time was not significantly different between the conventional colonoscopy and pan-colonic NBI system. The proportions of patients with at least one adenoma and those with multiple adenomas were not significantly different between groups. However, the pan-colonic NBI system significantly increased the total number of adenomas detected (P < 0.05) and the number of diminutive (<5 mm) adenomas detected (P < 0.05). The pan-colonic NBI system allowed detection of more diminutive adenomas in the distal colon than did conventional colonoscopy (P < 0.01), and more patients in the NBI group had at least one diminutive adenoma than in the control group (P < 0.05). Conclusions. The pan-colonic NBI system improves the total number of adenomas detected, including significantly more diminutive adenomas, without prolongation of extubation time. These results indicate that routine use of the NBI system for surveillance of diminutive adenomas may be recommended.

Using corticosteroids to reshape the gut microbiome: implications for inflammatory bowel diseases.

Abstract: BACKGROUND Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. METHODS Adult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts. RESULTS Exposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation. CONCLUSIONS Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists

Abstract: Narrow-band imaging (NBI) is a novel, noninvasive optical technique that uses reflected light to visualize the organ surface. However, few prospective studies that examine the efficacy of NBI screening for esophageal cancer have been reported. To compare the diagnostic yield of NBI endoscopy for screening of squamous mucosal high-grade neoplasia of the esophagus between experienced and less experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer received NBI endoscopic screening for esophageal neoplasia followed by chromoendoscopy using iodine staining. Biopsy specimens were taken from iodine-unstained lesions and the histological results of mucosal high-grade neoplasias served as the reference standard. The primary outcome was the sensitivity of NBI for detecting new lesions. The secondary outcome was the positive predictive value of NBI and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI in a per lesion basis. A total of 350 patients (170 by experienced endoscopists and 180 by less experienced endoscopists) underwent endoscopic examination. A total of 42 new mucosal high-grade neoplastic lesions (25 in the experienced endoscopist group and 17 in the less experienced endoscopist group) were detected. In the per-lesion-based analysis, the sensitivity was significantly higher in the experienced endoscopist group (100%; 25/25) compared with the less experienced endoscopist group (53%; 9/17) (P < 0.001). The positive predictive value of NBI was higher in the experienced endoscopist group than in the less experienced endoscopist group (45%, 25/55 vs. 35%, 9/26), although the difference was not significant (P = 0.50). The sensitivity of NBI in the less experienced endoscopist group was 43% in the former half of patients, and increased to 60% in the latter half of patients. In the per-patient-based analysis, the sensitivity of NBI was significantly higher in the experienced endoscopist group (100%) than in the less experienced endoscopist group (100 vs. 69%, respectively; P = 0.04). The positive predictive values of the experienced endoscopist group and the less experienced endoscopist group were similar, and were 48 and 47%, respectively. In conclusion, compared with the gold standard of chromoendoscopy with iodine staining, the sensitivity of NBI for screening of mucosal high-grade neoplasia was 100% with the experienced endoscopists but was low with the less experienced endoscopists. Electronic chromoendoscopy with NBI is a promising screening tool in these high-risk patients with esophageal mucosal high-grade neoplasia, particularly when performed by endoscopists with experience of using NBI.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Validation of clinical classification schemes for predicting stroke: results from the national registry of atrial fibrillation☆

Abstract: a c statistic of 0.82 (95% CI, 0.80-0.84), the CHADS2 index was the most accurate predictor of stroke. The stroke rate per 100 patient-years without antithrombotic therapy increased by a factor of 1.5 (95% CI, 1.3-1.7) for each 1-point increase in the CHADS2 score: 1.9 (95% CI, 1.2-3.0) for a score of 0; 2.8 (95% CI, 2.0-3.8) for 1; 4.0 (95% CI, 3.1-5.1) for 2; 5.9 (95% CI, 4.6-7.3) for 3; 8.5 (95% CI, 6.3-11.1) for 4; 12.5 (95% CI, 8.2-17.5) for 5; and 18.2 (95% CI, 10.5-27.4) for 6. Conclusion The 2 existing classification schemes and especially a new stroke risk index, CHADS2, can quantify risk of stroke for patients who have AF and may aid in selection of antithrombotic therapy.

Gut microbiota in the pathogenesis of inflammatory bowel disease

Abstract: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.

ERK/MAPK signalling pathway and tumorigenesis.

Abstract: Mitogen-activated protein kinase (MAPK) cascades are key signalling pathways that regulate a wide variety of cellular processes, including proliferation, differentiation, apoptosis and stress responses. The MAPK pathway includes three main kinases, MAPK kinase kinase, MAPK kinase and MAPK, which activate and phosphorylate downstream proteins. The extracellular signal-regulated kinases ERK1 and ERK2 are evolutionarily conserved, ubiquitous serine-threonine kinases that regulate cellular signalling under both normal and pathological conditions. ERK expression is critical for development and their hyperactivation plays a major role in cancer development and progression. The Ras/Raf/MAPK (MEK)/ERK pathway is the most important signalling cascade among all MAPK signal transduction pathways, and plays a crucial role in the survival and development of tumour cells. The present review discusses recent studies on Ras and ERK pathway members. With respect to processes downstream of ERK activation, the role of ERK in tumour proliferation, invasion and metastasis is highlighted, and the role of the ERK/MAPK signalling pathway in tumour extracellular matrix degradation and tumour angiogenesis is emphasised.

Inflammation: gearing the journey to cancer.

Abstract: Chronic inflammation plays a multifaceted role in carcinogenesis. Mounting evidence from preclinical and clinical studies suggests that persistent inflammation functions as a driving force in the journey to cancer. The possible mechanisms by which inflammation can contribute to carcinogenesis include induction of genomic instability, alterations in epigenetic events and subsequent inappropriate gene expression, enhanced proliferation of initiated cells, resistance to apoptosis, aggressive tumor neovascularization, invasion through tumor-associated basement membrane and metastasis, etc. Inflammation-induced reactive oxygen and nitrogen species cause damage to important cellular components (e.g., DNA, proteins and lipids), which can directly or indirectly contribute to malignant cell transformation. Overexpression, elevated secretion, or abnormal activation of proinflammatory mediators, such as cytokines, chemokines, cyclooxygenase-2, prostaglandins, inducible nitric oxide synthase, and nitric oxide, and a distinct network of intracellular signaling molecules including upstream kinases and transcription factors facilitate tumor promotion and progression. While inflammation promotes development of cancer, components of the tumor microenvironment, such as tumor cells, stromal cells in surrounding tissue and infiltrated inflammatory/immune cells generate an intratumoral inflammatory state by aberrant expression or activation of some proinflammatory molecules. Many of proinflammatory mediators, especially cytokines, chemokines and prostaglandins, turn on the angiogenic switches mainly controlled by vascular endothelial growth factor, thereby inducing inflammatory angiogenesis and tumor cell-stroma communication. This will end up with tumor angiogenesis, metastasis and invasion. Moreover, cellular microRNAs are emerging as a potential link between inflammation and cancer. The present article highlights the role of various proinflammatory mediators in carcinogenesis and their promise as potential targets for chemoprevention of inflammation-associated carcinogenesis.