Naoko Murano

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

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.

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

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.

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

BackgroundIntestinal 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.Subjects and MethodsFour groups of TNBS-induced colitis model were prepared using male SJL/J mice: A: Normal control group, B: control group, and C and D: treatment groups. The mucosal healing process was classified into three phases (an early phase: inflammation period, a mid-phase: regeneration promoting period, and a late phase: regeneration-converging period), and inflammation, the expression of fibrosis-related growth factors, and induction of apoptosis of fibrosis-related cells were compared in each period.Results(1) The clinical findings showed that SIMV showed anti-inflammatory effects with body weight gain and improvement of epithelial injury in the late phase. Histological (macroscopic/microscopic) improvement was noted in the mid- and late phases. The inflammatory cytokine (TNF-α) level significantly decreased in the mid- and late phases in the high-dose treatment group. (2) SIMV also had anti-fibrotic effects characterized by a dose-dependent decrease in the level of a fibrosis-related growth factor (CTGF) in the early and mid-phases, irrespective of inflammation or changes in the TGF-β1 level. Dose-dependent induction of apoptosis was noted in both fibroblasts and myofibroblasts from a relatively early stage.ConclusionsThe results suggested that SIMV induces anti-fibrotic activity that is not directly involved in the anti-inflammatory effect from a relatively early stage the healing process of TNBS-induced colitis.

Usefulness of polyethylene glycol solution with dimethylpolysiloxanes for bowel preparation before capsule endoscopy.

Background and Aim:  Capsule endoscopy (CE) is widely used for diagnosing small intestinal diseases. In some cases, however, observation of target sites is very poor during CE because of residues etc. Herein we report the usefulness of a preparation comprised of polyethylene glycol solution (PEG) for CE.

Therapeutic effect of nimesulide on colorectal carcinogenesis in experimental murine ulcerative colitis

Background:  Patients with ulcerative colitis (UC) exhibit an increased risk for the development of cancer of the colon and rectum. Cyclooxygenase (COX)‐2 inhibitors are known to suppress sporadic colorectal cancer, but it is unknown whether selective COX‐2 inhibitors exhibit a preventive effect in UC‐associated neoplasia. This study investigated the preventive effect of nimesulide, a selective COX‐2 inhibitor, on colorectal carcinogenesis in an experimental model of murine UC.

Primary CD56+ NK/T-cell lymphoma of the rectum accompanied with refractory ulcerative colitis.

A case of primary NK/T-cell lymphoma of the rectum accompanied with ulcerative colitis (UC) in a 73-year-old man is reported. He had a 6-year history of repeated admission to our hospital for UC. Total colonoscopy performed 4 months after resolution of refractory UC complicated by cytomegalovirus colitis showed a markedly submucosal tumor in the rectum, which was histologically diagnosed as malignant lymphoma. The findings of computed tomography of the chest and abdomen, gallium scintigraphy, abdominal ultrasonography, and upper gastrointestinal endoscopy showed no abnormal lesions. Therefore, based on a diagnosis of localized rectal lymphoma with UC, proctocolectomy was performed. The resected specimen showed three submucosal tumors in the rectum with local nodal involvement. Histologically, the tumors were characterized by diffusely infiltrating sheets of large atypical lymphoid cells, which were negative for CD4, CD8, and CD20 but were positive for CD56, CD3, and granzyme B. The presence of Epstein-Barr virus (EBV) infection in neoplastic cells was shown by in situ hybridization for EBV-encoded early small RNA1 (EBER-1). Based on these findings, the patient was diagnosed with primary CD56+ NK/T-cell lymphoma of the rectum (stage IIE). This is the first case report of primary rectal NK/T-cell lymphoma accompanied with UC.

Endoscopic and Histopathological Evaluation of Collagenous Colitis

Collagenous colitis (CC) is a well-known cause of chronic non-bloody diarrhea, especially in elderly women. CC is characterized histopathologically by an increase in the thickness of the subepithelial collagen layer to at least 10 µm, epithelial damage, and chronic inflammation of the lamina propria. Generally, the colonic mucosa in CC is macroscopically normal, although minor, non-specific abnormalities may be found. Due to the recent advancement of endoscopic and diagnostic technologies, however, microscopic mucosal abnormalities and specific longitudinal linear lacerations of the mucosa characteristic of CC have been identified. The association of CC with non-steroidal anti-inflammatory drugs and proton pump inhibitors has also been reported. Since definitive diagnosis of CC has to rely on pathologically documented collagen bands and mononuclear infiltration, the efficiency and precision of colonic biopsy need to be improved. Of the 29 CC patients that we have encountered at our institution, it was in 15 of 29 cases that the endoscopic finding that we performed a biopsy on was apparent. Our comparison of the endoscopic and histopathological findings of CC in the 15 patients showed that the mucosa frequently appeared coarse and nodular on the surface of the mucosa, which was also significantly thicker in collagen bands, demonstrating a strong correlation between collagen band formation and CC. Also, the coarse and nodular surface of the mucosa was most frequently seen affecting the proximal colon. The results suggest that endoscopic observation and biopsy of the proximal colon, where a coarse and nodular surface of the mucosa is often found, may be useful for confirmation of the diagnosis in patients with suspected CC.

Latent TGF‐β1‐transduced CD4+ T cells suppress the progression of allergic encephalomyelitis

Systemic injection of small amounts of transforming growth factor‐β (TGF‐β), a cytokine produced by lymphoid and other cells, has a profound effect in protecting mice from the nflammatory demyelinating lesions of experimental allergic encephalomyelitis (EAE; an animal model for multiple sclerosis). However, TGF‐β has side‐effects, which might be avoided if the cells producing TGF‐β can be delivered to the affected site in the nervous system to insure its local release in small amounts. Myelin basic protein (MBP)‐specific, cloned CD4+ T cells were engineered by retroviral transduction to produce latent TGF‐β. Studies about the spontaneous form of EAE in T cell receptor (TCR)‐transgenic recombination‐activating gene (RAG)‐1−/− mice showed that essentially all of the MBP‐specific, TCR‐transgenic RAG‐1−/− (BALB/c×B10.PL)F1 mice develop spontaneous EAE by the age of 11 weeks. By 12 weeks, 25–50% of the mice have died from disease. A single injection of TGF‐β1‐transduced T helper cell type 1 (Th1) cells significantly protected the mice from EAE, and untransduced Th1 cells did not protect. MBP‐specific BALB/c Th2 clones, transduced with TGF‐β1‐internal ribosome entry site‐green fluorescent protein (GFP) significantly reduced EAE induction by untransduced Th1 cells in RAG‐1−/− B10.PL mice. Furthermore, the GFP+ TGF‐β1‐producing Th2 cells were detectable in the spinal cords of the injected mice.

Colonoscopic differences of erosive and/or small ulcerative lesions for diagnosis of colonic inflammatory diseases.

Background and Aims:  Various etiologies and diseases may be related to erosive and/or small ulcerative lesions without gross appearance in the colon during colonoscopy. However, few investigators report on differential diagnosis of colonic inflammatory diseases. Thus, we investigated the clinical significance of these lesions and the value of colonoscopy in the differential diagnosis of colitis.

M1762 Simvastatin Attenuates Intestinal Fibrosis Independent of the Anti-Inflammatory Effect by Promoting Fibroblast/Myofibroblast Apoptosis on TNBS-Induced Mouse Colitis Model

G A A b st ra ct s inflammatory cells, and submucosal edema. [Result] Serum CyA levels were significantly less elevated after oral administration of CyA-MS than only CyA (CyA, 44.7±0.8ng/ml; CyAMS, 7.7±1.3ng/ml). The differences between CyA (0) and CyA (0)-MS was not significant in body weight, the histological score, MPO activity, and realtime RT-PCR. The body weight were significantly recovered in the mice group treated with CyA (0.2)-MS, CyA (2), and CyA (2)-MS compared with CyA (0)-MS. The percent body weight at day 10 compared with day 0 were as follows: CyA (0)-MS, -26.17±3.48%; CyA (0.2), -16.763±2.52%; CyA (0.2)-MS, -8.8±2.01%; CyA (2), -13.99±3.81%; and CyA (2)-MS, -7.53±1.97%, respectively. The histological score in CyA(0.2)-MS, CyA(2), and CyA(2)-MS were significantly less than CyA(0)-MS (78.2%, 83.9%, and 80.4%, respectively). The mice group treated with CyA (0.2)-MS was equally effective in histologically compared with that of CyA (2) and CyA (2)MS. MPO activity of the group treated with CyA-MS was also significantly lower than of those treated with vehicle, and data were as follows: CyA (0)-MS, 1.22±0.17unit/mg tissue; CyA (0.2)-MS, 0.73±0.17unit/mg tissue; and CyA (2)-MS, 0.67±0.17unit/mg tissue, respectively. Gene expressions of IL-1β, IL-6, and CXCL1, in the mice treated with CyA (0.2)-MS and CyA (2)-MS were down-regulated compared with the mice treated with CyA (0)-MS (37% and 24%, 11% and 13%, 11% and 14%, respectively). [Conclusion] CyA-MS might be possible to treat ulcerative colitis effectively by decreasing the total dosage without the elevation of the serum level or the side effects of CyA.