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 NSAIDinduced 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 111 Indium-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.

SUMMARYCytokines such as IL-1, tumour necrosis factor-alpha (TNF-a ), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor kB (NF-kB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NFkB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-a concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-kB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-kB antisense oligonucleotide may be effective in ulcerative colitis.

We examined the effect of intracolonic administration of anti-adhesion molecule antibodies on DSS-induced colitis in mice. Immunohistochemical staining in mice with colitis showed increased expression of ELAM-1 and ICAM-1 on endothelial cells of vessels in the lamina propria and submucosa at sites of inflamed lesions. Intracolonic administration of anti-ELAM-1 or anti-ICAM-1 antibody decreased bloody stools, anaemia, and histologically evident damage, as well as myeloperoxidase activity and IL-1beta content. We concluded that adhesion molecule expression is important in the development of DSS-induced colitis in mice and that intracolonic administration of anti-adhesion molecule antibodies, especially anti-ELAM-1 antibody, effectively inhibits the colonic inflammation. Intracolonic administration of anti-adhesion molecule antibodies may show therapeutic promise in ulcerative colitis.

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.

Background and Aim: Endoscopic submucosal dissection (ESD) is reported to be a safe and reliable procedure for the elderly, but these reports could have already had a bias at the time ESD was performed. However, the reports have not clearly stated the criteria of indications. In the present study, we retrospectively elucidated the usefulness and problems of ESD for early gastric cancer in elderly patients (Ն 65 years) in comparison with non-elderly patients. Methods: The subjects were selected from 412 consecutive patients with early gastric cancer (515 lesions) for which ESD was performed between June 2002 and February 2010. The following were used for analysis between groups: pre-and postoperative performance status (PS) of subjects, prevalence rates of pre-existing comorbidities, characteristics of lesions, treatment outcomes, durations of hospitalization, operating times, incidence rates of complications and durations of hospitalization, and postoperative hemorrhage rates, and duration of hospitalization in patients with anticoagulant therapy. Results: Of the lesions in the elderly, four patients (1.0%) were elderly with a PS of 3. The PS increased to six patients (1.6%) after the procedure. None of the non-elderly had a PS of 3 before or after the procedure. The ratio of patients with a pre-existing comorbidity was higher in the elderly than in the non-elderly. There were no differences between the two groups in the characteristics of the lesions, their duration of hospitalization, their operating times, or the incidence rates of complications. However, the elderly with perforations had a significantly longer hospitalization than the comparable non-elderly. The percentage of the patients taking anticoagulant drugs was significantly higher among the elderly. Of the patients on anticoagulant therapy, the duration of hospitalization tended to be longer in the elderly but no significant difference was found. None of the non-elderly with postoperative hemorrhage had received anticoagulant therapy. In the elderly with postoperative hemorrhage, 15.8% of the lesions were in those who had received anticoagulant therapy, indicating a significantly higher percentage of such lesions in the elderly group. Conclusion: We conclude that ESD is useful in elderly patients because there is a similar risk as for the non-elderly if the approach is individualized, and the following are taken into consideration when making the final decision of performing ESD in an elderly patient: patients should have a PS of 0, 1, or 2; determine whether or not anticoagulant therapy can be discontinued and whether or not treatment can be performed reliably without complications.