Tatsuo Ogihara

Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis

Background: Bacteria are implicated in certain forms of model chronic colitis but the identity and role of bacteria in human ulcerative colitis (UC) are uncertain. Aims: To isolate pathogenic bacteria from inflamed mucosa of patients with UC, to examine whether the bacteria have a toxin to Vero cells, and to determine whether the toxin induces UC-like lesions in animals. Methods: Bacteria were isolated from UC patients and supernatants from cultures were filtered and tested for cytotoxicity to Vero cells. Bacterial cells producing the cytotoxic supernatants were examined by polymerase chain reaction for verotoxin genes. Culture supernatants of cytotoxic strains were examined by high performance liquid chromatography for organic acid concentrations. Mice were given enemas containing organic acid at the mean concentration in the supernatants of cytotoxic strains to ascertain whether colonic lesions appear in UC. Results: Only supernatants from cultures of Fusobacterium varium killed Vero cells. Bacterial cells lacked verotoxin genes. Bacterial culture supernatants contained high concentrations of n-butyric acid and the mean concentration (32 mmol/l) was cytotoxic to Vero cells. Twenty four hours after mice were given enemas containing either butyric acid or F varium culture supernatants, colonic ulcers with crypt abscesses, inflammatory cell infiltration, and apoptotic changes were observed. Conclusions: Butyric acid in culture supernatants from cultures of F varium caused UC-like lesions in mice. This study indicates that F varium may be one of the elusive pathogenic factors in UC.

Endoscopic submucosal dissection of large colorectal tumors by using a novel spring-action S-O clip for traction (with video)

BACKGROUND Endoscopic submucosal dissection (ESD) allows en bloc resection of large GI neoplasms, regardless of their size; however, technical difficulties associated with ESD in the colorectum make it less widely applied in the treatment of tumors in this region. To address this difficulty, we designed a rubber strip-based traction device, called the S-O clip (Sakamoto-Osada clip) and reported previously that ESD with this device was effective for complete resection of large, superficial colorectal neoplasms. In this report, we describe a novel spring-action version of the S-O clip (spring S-O clip) that improves the facility of clip use during ESD of colorectal tumors. OBJECTIVE To evaluate the efficacy and safety of the spring S-O clip for ESD of colorectal neoplasms. DESIGN Case series. SETTING Juntendo University Hospital. MAIN OUTCOME MEASUREMENTS The efficacy and safety of the spring S-O clip traction device during ESD of colorectal tumors. RESULTS In 3 cases, a large, superficial neoplasm in the right side of the colon was removed safely and successfully en bloc without complication. Procedure times for the 3 cases were 44, 27, and 49 minutes, with resected specimens measuring 40, 24, and 35 mm, respectively. LIMITATION Uncontrolled study. CONCLUSION This limited case series demonstrates that spring S-O clip-assisted ESD is safe and effective for en bloc resection of large superficial neoplasms in the right side of the colon.

Appendectomy protects against the development of ulcerative colitis and reduces its recurrence: results of a multicenter case-controlled study in Japan

OBJECTIVES: Studies in the US and Europe have shown that appendectomy may prevent the development of ulcerative colitis, but no detailed study has been conducted in Japan, where ulcerative colitis is uncommon and the population is racially homogeneous. In addition, there has been no detailed analysis of the relationship between appendectomy and the clinical course of ulcerative colitis. In this multicenter clinical study, we evaluated the effects of appendectomy on ulcerative colitis in Japan. METHODS: A case-control study was undertaken in seven medical institutions comparing the incidence of appendectomy and tonsillectomy in 325 patients with ulcerative colitis and 325 controls matched for age (10-yr intervals) and sex. Disease duration, extent, and prognosis were determined in 21 patients with ulcerative colitis who underwent appendectomies and 304 patients with ulcerative colitis who did not undergo appendectomies. RESULTS: Appendectomy was performed in a significantly lower percentage of patients in the ulcerative colitis group (21/325, 6.5%) than in the control group (53/325, 16.3%) (p < 0.001) (odds ratios = 0.355, 95% CI = 0.208–0.603). In contrast, no significant difference was observed between the groups with respect to tonsillectomy. The mean age (25.7 ± 10.9 yr) of patients with ulcerative colitis at the time of appendectomy was significantly higher than the mean age (20.1 ± 8.7 yr) of patients in the control group at the time of appendectomy (p < 0.05). The incidence of proctitis was higher in the appendectomy group than in the group that did not undergo appendectomies (38.1% vs 18.1%). In addition, the recurrence rates were significantly lower in the appendectomy group than in the group that did not undergo appendectomies (57.1% vs 78.6%, p < 0.05), although both groups were similar in composition as to sex, age, duration of disease, smoking status, and previous medical treatment. CONCLUSIONS: Our results indicate that appendectomy has a negative association with and perhaps a preventive effect on the development of ulcerative colitis in the Japanese population. Furthermore, appendectomy also appears to reduce the extent and recurrence of ulcerative colitis.

Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.

Objective. It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC. Material and methods. Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3–5 months and 12–14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method. Results. The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3–5 and 12–14 months after the end of treatment compared with those in the control group (p=0.001–0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002–0.049). No serious drug-related toxicity was observed during the trial. Conclusions. The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.

Efficacy of reduced dosage of rabeprazole in PPI/AC therapy for Helicobacter pylori infection. Comparison of 20 and 40 mg rabeprazole with 60 mg lansoprazole.

Proton pump inhibitor (PPI)- based triple therapy has been a recent trend for treatment of Helicobacter pylori infection, with the PPI–amoxicillin–clarithromycin (PPI/AC) regimen being one of the most popular. We have reported the effectiveness of PPI/AC regimens in the Japanese population and have demonstrated that the effectiveness of 40 mg rabeprazole, a recently developed PPI, is similar to that of 40 mg of omeprazole and 60 mg of lansoprazole when used in combination with amoxicillin and clarithromycin. In this study, we focused on whether 20 mg of rabeprazole is effective in our patient population by comparing that dosage with 40 mg of rabeprazole and 60 mg of lansoprazole. In all, 308 H. pylori-infected patients [236 men and 72 women; age (mean ± sem) 49.3 ± 0.6 years] with peptic ulcer disease (N = 270) or nonulcer dyspepsia (N = 38) were randomly assigned to one of three different PPI/AC regimens for seven days: LAC (N = 104), consisting of lansoprazole 30 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; RAC (N = 104), consisting of rabeprazole 20 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day; and the R1/2AC regimen (N = 100), which included rabeprazole 10 mg twice a day, amoxicillin 500 mg three times a day, and clarithromycin 200 mg twice a day. Cure of the infection was determined by the [13C]urea breath test one month after completion of the treatment. Intention-to-treat based and per-protocol based cure rates for the LAC, RAC, and R1/2AC regimens were 82.7 (95% CI, 74–89) and 88.7% (81–94), 85.6 (77–92) and 89.8% (82–95), and 87.0 (79–93) and 89.7% (82–95), respectively. Although adverse effects were reported by 20.3% of the patients, these affected compliance in only five patients in the RAC and LAC regimens and none in the R1/2AC group. Overall complete compliance was achieved in 94.7% of interviewed patients. In conclusion, the effectiveness of the PPI/AC regimen with 20 mg of rabeprazole is comparable with and even safer than that of 40 mg of rabeprazole and 60 mg of lansoprazole in our patient population.

How useful is the detection kit for antibody to Helicobacter pylori in urine (URINELISA) in clinical practice

OBJECTIVE:Increased knowledge of the significance of Helicobacter pylori (H. pylori) infection in gastric disorders has accelerated the trend of screening patients with dyspepsia for its infection. Serological examination of antibody for H. pylori has been widely performed. Recently, a urine-based enzyme-linked immunosorbent assay (URINELISA) kit for detection of antibody for H. pylori has been developed. Accordingly, we evaluated its diagnostic accuracy in clinical practice.METHODS:Subjects of this study were 132 patients who presented at our university hospital because of dyspeptic symptoms (81 men, 51 women; age, 41.5 ± 1.4 yr). 13C urea breath test, blood drawing for serological antibody for H. pylori infection by four different kits, and urine collection for the URINELISA test for detection of the antibody were performed. Diagnostic accuracy of the commercially available antibodies in serum and in urine were investigated using the results of the 13C urea breath test as the gold standard.RESULTS:Sensitivity, specificity, and accuracy of URINELISA were 86.3% (95% confidence intervals [CI], 76–93%), 91.5% (95% CI, 81–97%), and 88.6% (95% CI, 82–93%), respectively, which were comparable to those of imported serological kits.CONCLUSIONS:The URINELISA kit for detecting anti-H. pylori antibody in urine provides diagnostic accuracy comparable to that of imported kits for detecting antibodies in serum and is considered to be clinically useful for the diagnosis of H. pylori infection.

Comparison of several activity indices for the evaluation of endoscopic activity in UC: inter- and intraobserver consistency.

Background: This study evaluated inter‐ and intraobserver agreement in the assessment of ulcerative colitis (UC) activity using 4 established indices and a newly designed Modified 6‐point Activity Index. Method: In all, 279 endoscopic pictures of inflammatory lesions from 93 UC patients were displayed twice to 4 expert and 4 trainee endoscopists, at an interval of 1 month. Each picture was assessed for inflammatory changes using established indices (Matts, Schroeder [a.k.a. Mayo Score], Baron, and Blackstone) and our new Modified 6‐point Activity Index. Weighted kappa statistics were used to estimate intra‐ and interobserver variation. Results: The Matts and Schroeder indices gave a “good” degree of concordance for expert endoscopists in terms of inter‐ and intraobserver agreements (0.74–0.78); this was not so evident with the Baron and Blackstone indices (0.61–0.73). For trainee endoscopists, all scores for inter‐ and intraobserver weighted kappa values using established indices (0.41–0.51) were lower than for the experts. The degree of concordance using the Modified 6‐point Activity Index was rated as “good” for inter‐ and intraobserver agreements for expert endoscopists (0.65 and 0.79), and as “moderate” for trainee endoscopists (0.54 and 0.64). Conclusions: Accurate assessment of UC disease activity from endoscopic findings benefited from experience. For expert endoscopists, the Matts and Schroeder indices proved the most reliable of the 4 established indices. Current endoscopic technologies may be adequate for assessing UC activity, particularly if modified to permit a finer classification of disease severity based on 6 grades, as with our newly developed Modified 6‐point Activity Index. (Inflamm Bowel Dis 2009;)

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy

Background : We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis.

Effect of Fasting Subjects’ Posture on 13C-Urea Breath Test for Detection of Helicobacter pylori Infection

Although many factors that may affect the 13C‐urea value have been verified, no literature is available regarding the effect of the posture of the patient on the shape of the Δ13C excretion curve. In an effort to contribute to the development of a simple and standard procedure for the 13C‐urea breath test, we investigated whether either the posture of the patient during the procedure or the mouthwash after dosing affects the shape of the Δ13C excretion curve.

NEWLY DEVELOPED AUTOFLUORESCENCE IMAGING VIDEOSCOPE SYSTEM FOR THE DETECTION OF COLONIC NEOPLASMS

Background:  Previously, we reported that most gastrointestinal tumors could be distinguished with the Light‐Induced Fluorescence Endoscopy for GastroIntestine system (LIFE‐GI system) using a fiberscope. However, the quality of the fiberscopic images was inferior compared with videoscopic images. Therefore, we developed a new Auto‐Fluorescence Imaging (AFI) videoscope system (manufactured by Olympus Corp.).