Munehiro Kugai

Ability of a novel blue laser imaging system for the diagnosis of colorectal polyps.

A new endoscope system with a laser light source, blue laser imaging (BLI), has been developed by Fujifilm that allows for narrow‐band light observation. The aim of the present study was to evaluate the utility of BLI for the diagnosis of colorectal polyps.

Efficacy of magnifying endoscopy with flexible spectral imaging color enhancement in the diagnosis of colorectal tumors.

BackgroundMagnifying endoscopy with flexible spectral imaging color enhancement (FICE) is an image-enhanced endoscopy that captures the surface and vascular patterns of colorectal tumors. We evaluated and compared FICE magnification to narrow-band imaging (NBI) magnification.MethodsFlexible spectral imaging color enhancement or NBI magnification was performed to the visualize surface and vascular patterns of colorectal tumors, classified into 4 types: Type A, Type B, Type C1/C2, and Type C3, as previously reported. A total of 235 colorectal tumors were examined. The correlations between classifications found by FICE or NBI magnification and histopathological diagnoses were examined. Image evaluation was validated by assessing inter-observer and intra-observer agreements on examinations.ResultsTwenty-eight hyperplastic polyps (HPs), 115 tubular adenomas (TAs), 72 mucosal and slightly invaded submucosal cancers (M-sSM), and 20 massively invaded submucosal cancers (mSM) were diagnosed. By FICE magnification, HP and TA were observed in 93.3 and 6.7% of Type A (15 lesions), respectively. TA, M-sSM, and HP were observed in 82.6, 15.4, and 2.0% of Type B (52 lesions), respectively. M-sSM, TA, and mSM were observed in 50.0, 46.0, and 4.0% of Type C1/2 (50 lesions), respectively. mSMs were observed in all 7 Type C3 lesions. In diagnosing mSM in Type C3, the sensitivity and specificity of FICE magnification were 77.7 and 100%, respectively, compared to those of NBI, at 63.6 and 99.0%, respectively. Imaging evaluation was validated accurately by intra- and intra-observer measurements showing consistent results.ConclusionsThe classification of colorectal tumors by FICE magnification correlated well with the histopathological diagnoses, similar to findings for NBI magnification. FICE magnification can be evaluated accurately with the same diagnostic classifications as those used for NBI magnification.

Endoscopic mucosal resection with 0.13% hyaluronic acid solution for colorectal polyps less than 20 mm: a randomized controlled trial.

Background and Aim:  Adequate mucosal elevation by submucosal injection is important for definitive en bloc resection and prevention of perforation during endoscopic mucosal resection (EMR). The objective of this study is to determine the efficacy of 0.13% hyaluronic acid (HA) solution for high and sustained mucosal elevation during colorectal EMR.

Acetyl salicylic acid induces damage to intestinal epithelial cells by oxidation-related modifications of ZO-1

Acetyl salicylic acid (ASA) is one of the most frequently prescribed medications for the secondary prevention of cardiovascular and cerebrovascular events. It has recently been reported to cause small intestinal mucosal injury at a considerably higher rate than previously believed. The aim of this study is to investigate the mechanism by which this occurs using an in vitro small intestine model focusing on the role of oxidative stress and cell permeability. Differentiated Caco-2 exhibits a phenotype similar to human small intestinal epithelium. We measured whether ASA induced the increase of differentiated Caco-2 permeability, the decrease of tight junction protein expression, the production of reactive oxygen species (ROS), and the expression of ROS-modified zonula occludens-1 (ZO-1) protein. In some experiments, Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, a superoxide dismutase mimetic) was used. The nontoxic concentration of ASA decreased transepithelial electrical resistance and increased the flux of fluorescein isothiocyanate-conjugated dextran across Caco-2 in a time-dependent manner. The same concentration of ASA significantly decreased ZO-1 expression among TJ proteins as assessed by Western blot and immunocytochemistry and increased ROS production and the expression of oxidative stress-modified ZO-1 protein. However, MnTMPyP suppressed the ASA-induced increased intercellular permeability and the ASA-induced ROS-modified ZO-1 expression. Our findings indicate that ASA-induced ROS production can specifically modify the expression of ZO-1 protein and induce increased cell permeability, which may ultimately cause small intestinal mucosal injury.

Efficacy of hyaluronic acid in endoscopic mucosal resection of colorectal tumors

Background and Aim:  Endoscopic mucosal resection (EMR) is the standard procedure for colorectal tumors. High mucosal elevation by submucosal injection is important for definite en bloc resection and the prevention of perforation. Hyaluronic acid (HA) is a reportedly useful injection solution for high and long‐lasting mucosal elevation, but the ideal HA concentration for optimization of mucosal elevation maintenance, injection pressure, and cost is unknown. In the present study, we assessed the appropriate concentration of HA for EMR.

The detection of surface patterns by flexible spectral imaging color enhancement without magnification for diagnosis of colorectal polyps

PurposeFlexible spectral imaging color enhancement (FICE), or image-enhanced endoscopy, can enhance visualization of surface and vascular patterns of colorectal polyps. Resolution of FICE has recently been improved. We evaluated diagnostic accuracy for neoplastic and non-neoplastic colorectal polyp differentiation with detection of surface patterns by FICE without magnification.MethodsRetrospective analysis of 151 colorectal polyps evaluated by FICE without magnification was performed. Neoplastic surface patterns were defined as tubular and oval pit. We aimed to determine sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy in correlating diagnosis by FICE without magnification with histology. Moreover, findings were compared to those of white-light endoscopy (WL) and chromoendoscopy (CHR).ResultsOf the 151 colorectal polyps, 95 were identified as neoplastic and 56 were identified as non-neoplastic. FICE without magnification had a sensitivity of 89.4%, specificity of 89.2%, PPV of 93.4%, NPV of 83.3%, and accuracy of 89.4%. The accuracy of FICE value was higher than that of WL (sensitivity of 74.7%, specificity of 73.2%, PPV of 82.5%, NPV of 63.0%, and accuracy of 74.1%) and was worse than that of CHR (sensitivity of 96.8%, specificity of 89.2%, PPV of 93.9%, NPV of 96.1%, and accuracy of 94.7%). Imaging evaluation was validated by inter-/intra-observer measurements, demonstrating consistent results.ConclusionsThe detection of surface patterns by FICE without magnification is useful for differential diagnosis of colorectal polyps. We believe that FICE without magnification is more convenient and easier method than CHR.

Prevention and Management of Complications of and Training for Colorectal Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) is reported to be an efficient treatment with a high rate of en bloc resection for large colorectal tumors in Japan and some other Western and Asian countries. ESD is considered less invasive than laparoscopic colectomy. However, ESD carries a higher risk of perforation than endoscopic mucosal resection (EMR). Various devices and training methods for colorectal ESD have been developed to solve the difficulties. In this review, we describe the complications of colorectal ESD and prevention of those complications. On the other hand, colorectal ESD is difficult for less-experienced endoscopists. The unique step-by-step ESD training system is performed in Japan. Additionally, appropriate training, including animal model training, for colorectal ESD should be acquired before working on clinical cases.

Hemin ameliorates indomethacin-induced small intestinal injury in mice through the induction of heme oxygenase-1

Although non‐steroidal anti‐inflammatory drugs can induce intestinal injury, the mechanisms are not fully understood, and treatment has yet to be established. Heme oxygenase‐1 (HO‐1) has recently gained attention for anti‐inflammatory and cytoprotective effects. This study aimed to investigate the effects of hemin, an HO‐1 inducer, on indomethacin‐induced enteritis in mice.

Prediction and treatment of difficult cases in colorectal endoscopic submucosal dissection.

Purpose. The aim of this study was to examine the characteristics of difficult cases and the learning curve in colorectal endoscopic submucosal dissection (ESD). Methods. We studied 518 colorectal tumors treated by ESD. Patients were divided into 2 groups such as the difficult ESD group and non-difficult ESD group in view of procedure time and procedure speed, respectively. The clinical features in each group were analyzed, and we also examined cases with severe fibrosis. Furthermore, we divided all cases into 5 periods according to experience of ESDs and investigated the rates of difficult and perforation cases. Results. In view of both procedure time and procedure speed, there were significant differences about mean tumor size, rates of severe fibrosis and perforation, and en bloc resection rate between the two groups. Severe fibrosis was detected in protruding tumors >40 mm in diameter. With respect to the learning curve, the rate of difficult and perforation cases decreased significantly in the late periods compared to the first period. Conclusions. Large tumor size, high rates of severe fibrosis and perforation, and low rate of en bloc resection are related with difficult ESD cases. The increasing of experiences can decrease the rate of difficult cases and perforation.

Role of metallothionein in murine experimental colitis

Metallothioneins (MTs) are a family of cysteine-rich low molecular-weight proteins that can act as reactive oxygen species scavengers. Although it is known that the induction of MT expression suppresses various inflammatory disorders, the role of MTs in intestinal inflammation remains unclear. In this study, we investigated the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the MT-I/II genes. Acute colitis was induced by 2% DSS in male MT-I/II double knockout (MT-null) and C57BL/6 (wild-type) mice. The disease activity index (DAI) was determined on a daily basis for each animal, and consisted of a calculated score based on changes in body weight, stool consistency and intestinal bleeding. Histology, colon length, myeloperoxidase (MPO) activity and colonic mRNA expression and the concentration of inflammatory cytokines were evaluated by real-time-PCR and enzyme-linked immunosorbent assay (ELISA). The localization of MTs and macrophages was determined by immunohistological and immunofluorescence staining. To investigate the role of MTs in macrophages, peritoneal macrophages were isolated and their responses to lipopolysaccharide were measured. Following DSS administration, the DAI score increased in a time-dependent manner and was significantly enhanced in the MT-I/II knockout mice. Colonic MPO activity levels and inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17] production increased following DSS administration, and these increases were significantly enhanced in the MT-I/II knockout mice compared with the wild-type mice. MT-positive cells were detected in the lamina propria and submucosal layer by immunohistochemical and immunofluorescence staining, and were mainly co-localized in F4/80-positive macrophages. The production of inflammatory cytokines (TNF-α, IFN-γ and IL-17) from isolated peritoneal macrophages increased following lipopolysaccharide stimulation, and these increases were significantly enhanced in the macrophages obtained from the MT-I/II knockout mice. These data indicate that MTs play an important role in the prevention of colonic mucosal inflammation in a mouse model of DSS-induced colitis, thus suggesting that endogenous MTs play a protective role against intestinal inflammation.