Eijiro Morita

Present status and strategy of NSAIDs-induced small bowel injury

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known to cause gastroduodenal mucosal lesions as an adverse effect. Recently, the serious problem of NSAID-induced small intestinal damage has become a topic of great interest to gastroenterologists, since capsule endoscopy and balloon enteroscopy are available for the detection of small intestinal lesions. Such lesions have been of great concern in clinical settings, and their treatment and prevention must be devised as soon as possible. The prevalence of NSAIDs-induced small intestinal injury is higher than had been expected. Recent studies show that more than 50% of patients taking NSAIDs have some mucosal damage in the small intestine. The gross appearance of NSAID-induced enteropathy varies, appearing variously as diaphragm-like strictures, ulcers, erosions, and mucosal redness. To investigate NSAID-induced enteropathy, and to rule out other specific enteropathies, other useful methods (in addition to capsule endoscopy and balloon enteroscopy) include such modalities as radiological examination of the small intestine, the permeability test, scintigraphy or the fecal excretion test using 111Indium-labeled white blood cells, and measurement of the fecal calprotectin concentration. Diaphragm-like strictures and bleeding from mucosal breaks may be treatable with interventional enteroscopy. Misoprostol, metronidazole, and sulfasalazine are frequently used to treat NSAID-induced enteropathy, but have undesirable effects in some cases. In the experimental model, we confirmed that several existing drugs for gastroduodenal ulcers prevented indomethacin-induced small intestinal injury. Such drugs may be useful for preventing the adverse effects of NSAIDs not only in the stomach but also in the small intestine. We hope to examine these drugs in future clinical studies.

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.

In vivo trial of a driving system for a self-propelling capsule endoscope using a magnetic field (with video).

BACKGROUND A capsule endoscope does not allow the examiner to observe a lesion from the desired direction in real time. OBJECTIVE To develop a driving system for a self-propelling capsule endoscope (SPCE) by using a magnetic field. SETTING Experimental endoscopic study in a live dog model. DESIGN AND INTERVENTIONS A microactuator was developed with the aim of remote-control operation. We developed a driving system for SPCE by attaching a capsule endoscope to this medical microactuator and performed the following experiments. (1) We operated this SPCE by remote control in the stomach of a dog under sedation and obtained endoscopic images using a real-time monitoring system only. (2) We placed a hemostatic clip on the gastric mucosa and recorded images of this clip with the SPCE. (3) We also placed clips at 2 other sites in the stomach and asked the SPCE operator, who was unaware of the location of the clips, to identify the site, number, and color of the clips. MAIN OUTCOME MEASUREMENTS Evaluation of performance of a driving system for SPCE. RESULTS The operator was able to obtain endoscopic images with the SPCE in the stomach of a dog in vivo, in any desired direction, by remote control. SPCE produced clear images of the clips placed in the stomach. The operator was able to easily identify the site, number, and color of the clips. LIMITATIONS Animal model. CONCLUSIONS Our trial suggests the possibility of clinical application of the driving system for an SPCE using a magnetic field.

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.

Evaluation of Portal Hypertensive Enteropathy by Scoring with Capsule Endoscopy: Is Transient Elastography of Clinical Impact?

There is limited data about the mucosal lesions of portal hypertensive enteropathy (PHE) detected by capsule endoscopy, and there is no scoring system to evaluate their severity. Our aim is to create a reliable scoring system for PHE, and to explore the possible usefulness of using transient elastograhy (TE) in that field. We compared the medical records of 31 patients with liver cirrhosis and portal hypertension with 29 control patients. We found that the mucosal lesions compatible with PHE were significantly more common in cirrhotic patients than in control patients (67.7% vs 6.9%, p<0.001). Cirrhotic patients with high TE score (p = 0.018), high Child-Pugh grade, large esophageal varices (EV), portal hypertensive gastropathy, and history of endoscopic variceal injection sclerotherapy or ligation (EIS/EVL) were significantly associated with PHE. Using our scoring system, we found that patients with higher TE score (p = 0.004), high Child-Pugh score (p = 0.011), larger EV (p = 0.006), and prior EIS/EVL (p = 0.006) were significantly associated with higher PHE score. We concluded that using our scoring system might be helpful in grading PHE severity, and TE might be a new non-invasive method for detecting the presence and severity of PHE in cirrhotic patients.

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.

Blue mode imaging may improve the detection and visualization of small-bowel lesions: A capsule endoscopy study.

Background/Aims: Diagnostic miss rate and time consumption are the two challenging limitations of small-bowel capsule endoscopy (SBCE). In this study, we aimed to know whether using of the blue mode (BM) combined with QuickView (QV) at a high reviewing speed could influence SBCE interpretation and accuracy. Materials and Methods: Seventy CE procedures were totally reviewed in four different ways; (1) using the conventional white light, (2) using the BM, [on a viewing speed at 10 frames per second (fps)], (3) using white light, and (4) using the BM (on a viewing speed at 20 fps). In study A, the results of (1) were compared with those of (2), and in study B, the results of (3) and (4) were separately compared with those of (1). Results: In study A, the total number of the vascular (P < 0.001) and the inflammatory lesions (P = 0.005) detected by BM was significantly higher than that detected by the white light. No lesion was found using the white light that was not detected by the BM. Moreover, the BM highly improved the image quality of all the vascular lesions and the erythematous ones from the nonvascular lesions. In study B, the total number of only the vascular lesions, detected by the BM on a rapid speed of viewing at 20 fps was significantly higher than that detected by the white light (P = 0.035). However, the true miss rate for the BM was 4%. Conclusion: BM imaging is a new method that improved the detection and visualization of the vascular and erythematous nonvascular lesions of SB as compared with the conventional white light imaging. Using of the BM at a slow viewing speed, markedly reduced the diagnostic miss rate of CE.

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.