[Show abstract][Hide abstract] ABSTRACT: The antibiotics, metronidazole and ciprofloxacin, are the first-line treatment for pouchitis. Patients who do not respond to antibiotics or conventional medications represent a major challenge to therapy. In this report, we have described a successful treatment of severe refractory pouchitis with a novel agent, rebamipide, known to promote epithelial cell regeneration and angiogenesis. A 27-year-old male with ileo-anal pouch surgery presented with worsening anal pain, diarrhea, and abdominal pain. The patient was diagnosed to have pouchitis and was given metronidazole together with betamethasone enema (3.95 mg/dose). However, despite this intensive therapy, the patient did not improve. On endoscopy, ulceration and inflammation were seen in the ileal pouch together with contact bleeding and mucous discharge. The patient was treated with rebamipide enema (150 mg/dose) twice a day for 8 wk without additional drug therapy. Two weeks after the rebamipide therapy, stool frequency started to decrease and fecal hemoglobin became negative at the 4th wk. At the end of the therapy, endoscopy revealed that ulcers in the ileal pouch had healed with no obvious inflammation. The effect of rebamipide enema was dramatic and was maintained throughout the 11-mo follow-up. The patient continued to be in remission. No adverse effects were observed during the treatment or the follow-up period. The sustained response seen in this case with severe and refractory pouchitis indicates that agents, which promote epithelial cell growth, angiogenesis and mucosal tissue regeneration, are potential therapeutic agents for the treatment of refractory colorectal lesions.
World Journal of Gastroenterology 02/2006; 12(4):656-8. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study we investigated the effect of rebamipide enema in patients with steroid-resistant and/or dependent ulcerative colitis. Rebamipide enemas were administered twice daily for a 12-week period; this treatment was further continued longer in patients who requested this. Disease activity index as reflecting the clinical condition and endoscopic index with histological grading were determined before and after the treatment period. Nine of 11 (81.8%) patients on 12-week treatment with rebamipide approved and were classified as colitis in remission. Moreover, seven of 11 patients requested long-term medication, the longest medication term being 80 weeks. These results medicated that rebamipide enemas may be effective in patients with steroid-resistant and/or dependent ulcerative colitis.
[Show abstract][Hide abstract] ABSTRACT: Background: The incidence rate after a colonoscopic polypectomy includes the true incidence rate of new polyp formation and miss rate of polyps at the initial colonoscopy. It is therefore important to assess accurate incidence rates of polyps as well as those of missing polyps with colocoscopy.Methods: Six hundred and eighty-eight patients who underwent total colonoscopy twice within 30 days were investigated to determine the miss rates of neoplastic polyps under colonoscopy. The cumulative incidence rates of neoplasm were evaluated by the Kaplan-Meier method in another series of investigations on 864 patients who underwent surveillance total colonoscopy over 31 days.Results: In 157 (22.8%) patients out of 688, 200 neoplastic lesions (all adenomas) were missed during the first examination. The miss rate was 16% for adenomas ≤ 5 mm and 2% for adenomas > 10 mm. The miss rates of patients with 0, 1, 2, or > 2 neoplastic polyps on the first examination was 5.3%, 19.6%, 23.5% and 35.5%, respectively. One year cumulative incidence rates of patients with 1, 2, or > 2 neoplastic polyps on the first examination were 18.4%, 21.1% and 34.2%, respectively.Conclusion: Detection of multiple neoplasms on index colonoscopy predicts a high miss rate and cumulative incidence rate on surveillance colonoscopy. A substantial proportion of neoplasms detected at nearly 1-year postpolypectomy surveillance colonoscopy were missed at the initial total colonoscopy.
[Show abstract][Hide abstract] ABSTRACT: E-cadherin expressed on gastric epithelium is reported to form adherence junctions and stabilize barrier functions. While hypoxia-reoxygenation is well known to cause gastric mucosal injury during reoxygenation, gastric E-cadherin actions against this stress remain unclear. In this study, using the oxygen depleting agent thioglycolic acid we examined whether E-cadherin expressed on rat cultured gastric epithelial cells has protective actions against epithelial barrier dysfunction induced by chemical hypoxia-reoxygenation.
Chemical hypoxia was induced by incubating cells with 5 mm thioglycolic acid in glucose free medium for 60 min. Cells were then reoxygenated for 240 min by changing to normal medium. The expression of E-cadherin on the cell surface was measured with an enzyme immunoassay, and epithelial permeability was determined by the diffusion rate of FITC-dextran through the cell layer.
E-cadherin expression increased during the 60 min hypoxic period, accompanied by activation of protein kinase C, protein kinase G and protein kinase A. The increased expression significantly diminished, but was considerably higher than the control values during reoxygenation for 180 min, which was partially due to generation of reactive oxygen species but not to activation of protein kinase. Conversely, epithelial permeability was stabilized during hypoxia, but increased only for 30 min of reoxygenation, probably due to generation of reactive oxygen species. Epithelial permeability during hypoxia was elevated by a combination of all the protein kinase inhibitors.
An increase in the expression of E-cadherin during hypoxia through the activation of the kinases is likely to stabilize epithelial barrier functions. The reactive oxygen species generated during 30 min reoxygenation increased the molecular expression of E-cadherin less than during hypoxic stress. The transient break in the barrier functions caused by reactive oxygen species during reoxygenation appears to overcome the reactive oxygen species mediated cytoprotective action increasing E-cadherin expression.
European Journal of Gastroenterology & Hepatology 01/2003; 14(12):1295-302. DOI:10.1097/00042737-200212000-00002 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We previously reported that the intracutaneous injection of DNA vaccines encoding Helicobacter pylori heat shock proteins elicited specific immune responses, and led to reduced infection in mice. In this study, we constructed DNA vaccine encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in the sera of intranasal and intracutaneous immunized mice. Both intranasal and intracutaneous immunized mice were significantly protected from colonization by H. pylori and had significantly reduced degrees of gastritis. These results demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune response against H. pylori, and that intranasal immunization works as well as intracutaneous immunization.
[Show abstract][Hide abstract] ABSTRACT: E-cadherin, which is a [Ca2+]-dependent, homotypic cell-cell adhesion molecule, is expressed in gastrointestinal epithelial cells. Much has been learned about the down-regulation of E-cadherin expression in gastrointestinal tumours, Barrett's oesophageal dysplasia, and Crohn's disease, but the functions of this molecule in normal gastrointestinal mucosa are less known.
In this study, we investigated the relationship between E-cadherin expression and permeability using rat cultured gastric and intestinal epithelial cells following a 30-min exposure to various pH solutions. We also investigated the participation of [Ca2+] in these events.
E-cadherin expression increased under acid (pH 4) but not alkali (pH 10 or 11) exposure only for gastric epithelial cells. Gastric epithelial permeability was maintained only against acid exposure while intestinal permeability increased under both conditions. Transient influx of [Ca2+] was only observed for gastric epithelial cells just after acid exposure.
These findings suggest that E-cadherin expression on gastric epithelium stabilizes the epithelial barrier against acid, probably through influx of [Ca2+]. This event is thought to be one of the protective mechanisms in gastric mucosa against acid back-diffusion, which is one of the causes of peptic ulcer formation.
European Journal of Gastroenterology & Hepatology 03/2001; 13(2):127-36. DOI:10.1097/00042737-200102000-00007 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although endoscopic mucosal resection (EMR) for early gastric cancer (EGC) without ulceration or scarring has been very popular in Japan and thought to be beneficial, curability by EMR is still lower than that for surgical resection. We investigated patients whose EGCs were resected endoscopically in order to identify the factors affecting curability by EMR.
We investigated retrospectively 256 EGC lesions (251 patients) which were subjected to EMR between 1989 and 1998 with respect to patient profile, macroscopic type, location, maximum diameter of tumors, resection method and histological typing. The prognoses of the patients were also investigated as far as possible.
The curative total resection rate for EMR of EGC was 74.2 %. Concerning the factors affecting curability, the size of the lesion (over 15 mm), the method of resection (divisional resection), and histological typing (poorly differentiated) had a statistically significant effect on the complete resection rate. Multivariate analysis of the factors confirmed these results. Submucosal invasion was suspected in 16 patients after EMR, but submucosal cancer was found in only one patient after further surgery. Where there was recurrence, the longest recurrence-free period after EMR of EGC was 48 months, whereas the mean recurrence-free period was 195.4 days.
The appropriate indication for EMR for EGC is thought to be an intramucosal differentiated-type adenocarcinoma without ulceration or scarring, and no more than 15 mm in size regardless of macroscopic type. Periodic follow-up for at least 5 years is necessary.
[Show abstract][Hide abstract] ABSTRACT: A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation. Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.
Internal Medicine 09/2000; 39(8):626-31. · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 29-year-old man was admitted to our hospital with a history of recurrent right upper quadrant abdominal pain and vomiting. These symptoms appeared intermittently for 7 years. Various examinations revealed a diagnosis of midgut malrotation, Laparotomy was performed and revealed reverse rotation of the duodenum with paraduodenal hernia and a normal rotating colon. This case suggests that recurrent abdominal complaints in an adult should arouse suspicion of midgut malrotation.
Internal Medicine 08/2000; 39(8):626-631. DOI:10.2169/internalmedicine.39.626 · 0.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case of carcinoma in solitary rectal ulcer syndrome. The diagnosis was made by colonoscopic appearance and biopsy. A tumor measuring 0.9 x 0.6 cm was found in a resected solitary rectal ulcer. The lesion exhibited typical histological features of solitary rectal ulcer syndrome, with a well differentiated adenocarcinoma invading submucosal layers and some dysplastic glands. We believe that the adenocarcinoma represents a malignant transformation from solitary rectal ulcer syndrome, because similar to longstanding chronic idiopathic colitis, colorectal dysplasia and carcinoma may develop.
The American Journal of Gastroenterology 12/1998; 93(11):2235-8. DOI:10.1111/j.1572-0241.1998.00622.x · 9.21 Impact Factor