Small-bowel capsule endoscopy (SBCE)
 1 ESGE recommends that prior to SBCE patients ingest a purgative (2 L of polyethylene glycol [PEG]) for better visualization. Strong recommendation, high quality evidence. However, the optimal timing for taking purgatives is yet to be established. 2 ESGE recommends that SBCE should be performed as an outpatient procedure if possible, since completion rates are higher in outpatients than in inpatients. Strong recommendation, moderate quality evidence. 3 ESGE recommends that patients with pacemakers can safely undergo SBCE without special precautions. Strong recommendation, low quality evidence. 4 ESGE suggests that SBCE can also be safely performed in patients with implantable cardioverter defibrillators and left ventricular assist devices. Weak recommendation, low quality evidence. 5 ESGE recommends the acceptance of qualified nurses and trained technicians as prereaders of capsule endoscopy studies as their competency in identifying pathology is similar to that of medically qualified readers. The responsibility of establishing a diagnosis must however remain with the attending physician. Strong recommendation, moderate quality evidence. 6 ESGE recommends observation in cases of asymptomatic capsule retention. Strong recommendation, moderate quality evidence. In cases where capsule retrieval is indicated, ESGE recommends the use of device-assisted enteroscopy as the method of choice. Strong recommendation, moderate quality evidence. Device-assisted enteroscopy (DAE)
 1 ESGE recommends performing diagnostic DAE as a day-case procedure in patients without significant underlying co-morbidities; in patients with co-morbidities and/or those undergoing a therapeutic procedure, an inpatient stay is recommended. Strong recommendation, low quality evidence The choice between different settings also depends on sedation protocols. Strong recommendation, low quality evidence. 2 ESGE suggests that conscious sedation, deep sedation, and general anesthesia are all acceptable alternatives: the choice between them should be governed by procedure complexity, clinical factors, and local organizational protocols. Weak recommendation, low quality evidence. 3 ESGE recommends that the findings of previous diagnostic investigations should guide the choice of insertion route. Strong recommendation, moderate quality evidence. If the location of the small-bowel lesion is unknown or uncertain, ESGE recommends that the antegrade route should be generally preferred. Strong recommendation, low quality evidence. In the setting of massive overt bleeding, ESGE recommends an initial antegrade approach. Strong recommendation, low quality evidence. 4 ESGE recommends that, for balloon-assisted enteroscopy (i. e., single-balloon enteroscopy [SBE] and double-balloon enteroscopy [DBE]), small-bowel insertion depth should be estimated by counting net advancement of the enteroscope during the insertion phase, with confirmation of this estimate during withdrawal. Strong recommendation, low quality evidence. ESGE recommends that, for spiral enteroscopy, insertion depth should be estimated during withdrawal. Strong recommendation, moderate quality evidence. Since the calculated insertion depth is only a rough estimate, ESGE recommends placing a tattoo to mark the identified lesion and/or the deepest point of insertion. Strong recommendation, low quality evidence. 5 ESGE recommends that all endoscopic therapeutic procedures can be undertaken at the time of DAE. Strong recommendation, moderate quality evidence. Moreover, when therapeutic interventions are performed, additional specific safety measures are needed to prevent complications. Strong recommendation, high quality evidence.

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Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that form a family of 24 members in mammals. Evidence of the pathological roles of MMPs in various diseases, combined with their druggability, has made them attractive therapeutic targets. Initial drug discovery efforts focused on the roles of MMPs in cancer progression, and more than 50 MMP inhibitors have been investigated in clinical trials in various cancers. However, all of these trials failed. Reasons for failure include the lack of inhibitor specificity and insufficient knowledge about the complexity of the disease biology. MMPs are also known to be involved in several inflammatory processes, and there are new therapeutic opportunities for MMP inhibitors to treat such diseases. In this Review, we discuss the recent advances made in understanding the role of MMPs in inflammatory diseases and the therapeutic potential of MMP inhibition in those conditions.

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Is there new hope for therapeutic matrix metalloproteinase inhibition

It is unclear whether TGF-β, a critical differentiation factor for T cells producing interleukin 17 (TH-17 cells), is required for the initiation of experimental autoimmune encephalomyelitis (EAE) in vivo. Here we show that mice whose T cells cannot respond to TGF-β signaling lack TH-17 cells and do not develop EAE despite the presence of T helper cell type 1 infiltrates in the spinal cord. Local but not systemic antibody blockade of TGF-β prevented TH-17 cell differentiation and the onset of EAE. The pathogen stimulus zymosan, like mycobacterium, induced TH-17 cells and initiated EAE, but the disease was transient and correlated with reduced production of interleukin 23. These data show that TGF-β is essential for the initiation of EAE and suggest that disease progression may require ongoing chronic inflammation and production of interleukin 23.

Signals mediated by transforming growth factor-beta initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease.

This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the role of advanced endoscopic imaging for the detection and differentiation of colorectal neoplasia. Main recommendations
 1 ESGE suggests the routine use of high definition white-light endoscopy systems for detecting colorectal neoplasia in average risk populations (weak recommendation, moderate quality evidence). 2 ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (narrow band imaging [NBI], i-SCAN) chromoendoscopy in patients with known or suspected Lynch syndrome (strong recommendation, low quality evidence). 2b ESGE recommends the routine use of high definition systems and pancolonic conventional or virtual (NBI) chromoendoscopy in patients with known or suspected serrated polyposis syndrome (strong recommendation, low quality evidence). 3 ESGE recommends the routine use of 0.1 % methylene blue or 0.1 % – 0.5 % indigo carmine pancolonic chromoendoscopy with targeted biopsies for neoplasia surveillance in patients with long-standing colitis. In appropriately trained hands, in the situation of quiescent disease activity and adequate bowel preparation, nontargeted, four-quadrant biopsies can be abandoned (strong recommendation, high quality evidence). 4 ESGE suggests that virtual chromoendoscopy (NBI, FICE, i-SCAN) and conventional chromoendoscopy can be used, under strictly controlled conditions, for real-time optical diagnosis of diminutive (≤ 5 mm) colorectal polyps to replace histopathological diagnosis. The optical diagnosis has to be reported using validated scales, must be adequately photodocumented, and can be performed only by experienced endoscopists who are adequately trained and audited (weak recommendation, high quality evidence). 5 ESGE suggests the use of conventional or virtual (NBI) magnified chromoendoscopy to predict the risk of invasive cancer and deep submucosal invasion in lesions such as those with a depressed component (0-IIc according to the Paris classification) or nongranular or mixed-type laterally spreading tumors (weak recommendation, moderate quality evidence). Conclusion
 Advanced imaging techniques will need to be applied in specific patient groups in routine clinical practice and to be taught in endoscopic training programs.

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Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

In patients with IBD, chronic colonic inflammation increases the risk of colorectal cancer, perhaps because inflammation predisposes these tissues to genomic instability. Carcinogenesis in the inflamed colon seems to follow a different sequence of genetic alterations than that observed in sporadic cancers in the uninflamed colon. In this Review, we focus on the genetic alterations in colitis-associated colorectal cancer that contribute to the acquisition of the essential hallmarks of cancer, and on how those alterations differ from sporadic colorectal cancers. Our intent is to provide a conceptual basis for categorizing carcinogenetic molecular abnormalities in IBD, and for understanding how cancer-preventive therapies might target reversal of acquired abnormalities in specific biochemical pathways.

Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer

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.

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

Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of colitis. Recent studies have demonstrated that chymase is involved in the conversion of promatrix metalloproteinase (proMMP)-9 to MMP-9. However, whether chymase contributes to the activation of proMMP-9 in colitis has remained unclear. In this study, we administered 5% dextran sodium sulfate (DSS) solution to mice for 7 days. At 7 days after starting administration, both chymase activity and MMP-9 activity were significantly increased. In extract from colitis in DSS-treated mice, MMP-9 activity was significantly increased after 8 h of incubation, but increased activity was almost completely suppressed in the presence of a chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl] acetamide (NK3201). At 7 days after starting administration, intestinal length was significantly shorter in DSS-treated mice than in normal mice, but these changes were significantly prevented by NK3201 (10 mg/kg per day i.p.). Disease activity index and histological damage score were also significantly reduced by NK3201. The filtrated neutrophil number was significantly decreased by NK3201. Furthermore, NK3201 significantly attenuated not only chymase activity but also MMP-9 activity in DSS-treated mice. These findings suggest that chymase plays an important role in the development of colitis via MMP-9 activation.

Role of Chymase-Dependent Matrix Metalloproteinase-9 Activation in Mice with Dextran Sodium Sulfate-Induced Colitis

Background
Intestinal deformity and stenosis are induced by fibrosis during the process healing of intestinal chronic inflammation in inflammatory bowel disease (IBD). Potent anti-inflammatory treatment of patients with Crohn’s disease (CD) may induce fibrous stenosis, and this is often difficult to treat in clinical practice. Therefore, it is necessary to develop a treatment strategy that concomitantly exhibits repair/regenerative and anti-fibrotic effects, in addition to the current anti-inflammatory effect, for the treatment of inflammatory bowel diseases. However, the relationship between the course of inflammatory activity and the healing process and fibrogenesis has not been elucidated; although the complex involvement of various factors in the mechanism of biological fibrosis has been investigated. Simvastatin (SIMV), an HMG-CoA reductase inhibitor, exhibits anti-inflammatory and anti-fibrotic effects. The current study established a model of the regeneration/healing process from TNBS-induced colitis and investigated the anti-inflammatory and anti-fibrotic effects of SIMV.

Simvastatin Attenuates Intestinal Fibrosis Independent of the Anti-Inflammatory Effect by Promoting Fibroblast/Myofibroblast Apoptosis in the Regeneration/Healing Process from TNBS-Induced Colitis

AIM: To evaluate the effect of pyrrolidine dithio-carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis.

METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupI(low-dose group), and DSS+PDTC-treated groupII (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured.

RESULTS: The DSS+PDTC-treated groupII exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC-treated groupII.

CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.

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Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis.

Comparative Study of Conventional Colonoscopy and Pan-Colonic Narrow-Band Imaging System in the Detection of Neoplastic Colonic Polyps: A Randomized, Controlled Trial

Naoko Murano

Papers

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

Role of Chymase-Dependent Matrix Metalloproteinase-9 Activation in Mice with Dextran Sodium Sulfate-Induced Colitis

Simvastatin Attenuates Intestinal Fibrosis Independent of the Anti-Inflammatory Effect by Promoting Fibroblast/Myofibroblast Apoptosis in the Regeneration/Healing Process from TNBS-Induced Colitis

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis.

Comparative Study of Conventional Colonoscopy and Pan-Colonic Narrow-Band Imaging System in the Detection of Neoplastic Colonic Polyps: A Randomized, Controlled Trial