Takeshi Terai

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.

Correlations among total colonoscopic findings, clinical symptoms, and laboratory markers in ulcerative colitis

Background and Aim:  Colonoscopy plays an integral role in the diagnosis, management and surveillance of ulcerative colitis (UC). In the present study we assessed the relationship between endoscopic and histological findings, clinical symptoms, and laboratory data.

Increased esophageal sensitivity to acid and saline in patients with nonerosive gastro-esophageal reflux disease

Goals To investigate the features of nonerosive reflux disease (NERD). Background NERD is not considered as a milder form of erosive gastro-esophageal reflux disease (eGERD). Although the prevalence of NERD was reported to be high in our country, there have been very few studies about NERD. Study We performed upper gastrointestinal endoscopy to confirm the diagnosis of GERD. The modified acid perfusion test and saline perfusion test were performed in 7 control subjects, 14 NERD, and 11 eGERD patients. The stimulus-response function to acid and saline was quantified by the duration of typical symptom perception (minutes), total sensory intensity rating (0 to 10), and the perfusion sensory score (SS), which was defined as the product of minutes and the sensory intensity rating. Results The mean value of SS by saline was 0 in control subjects, 12.0 in NERD patients, and 1.5 in eGERD patients (P<0.01 control vs. NERD, P<0.01 NERD vs. eGERD). The mean SS with acid was 0.9 in control subjects, 52.5 in NERD patients, and 23.0 in eGERD patients (P<0.01 control vs. NERD, control vs. eGERD, P<0.05 NERD vs. eGERD). A statistically significant association was shown between the acid and saline perfusion SSs with a correlation coefficient value of r=0.57 in the NERD group (P<0.05). Conclusions Both eGERD and NERD, but especially NERD, exhibited esophageal hypersensitivity not only to acid but also saline perfusion, suggesting that hyperalgesia to acid and other factors (eg, psychologic and/or autonomic nerve disturbance) may play some roles in symptom generation in NERD.

Narrow-band imaging (NBI) magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team.

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

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.

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.

NBI magnifying endoscopic classification of colorectal tumors proposed by the Japan NBI Expert Team (JNET)

Many clinical studies on narrow‐band imaging (NBI) magnifying endoscopy classifications advocated so far in Japan (Sano, Hiroshima, Showa, and Jikei classifications) have reported the usefulness of NBI magnifying endoscopy for qualitative and quantitative diagnosis of colorectal lesions. However, discussions at professional meetings have raised issues such as: (i) the presence of multiple terms for the same or similar findings; (ii) the necessity of including surface patterns in magnifying endoscopic classifications; and (iii) differences in the NBI findings in elevated and superficial lesions. To resolve these problems, the Japan NBI Expert Team (JNET) was constituted with the aim of establishing a universal NBI magnifying endoscopic classification for colorectal tumors (JNET classification) in 2011. Consensus was reached on this classification using the modified Delphi method, and this classification was proposed in June 2014. The JNET classification consists of four categories of vessel and surface pattern (i.e. Types 1, 2A, 2B, and 3). Types 1, 2A, 2B, and 3 are correlated with the histopathological findings of hyperplastic polyp/sessile serrated polyp (SSP), low‐grade intramucosal neoplasia, high‐grade intramucosal neoplasia/shallow submucosal invasive cancer, and deep submucosal invasive cancer, respectively.

Frequent hypermethylation of RASSF1A in early flat-type colorectal tumors

Flat colorectal tumors, characterized by high-grade dysplasia from early small flat mucosal lesions, exhibit a relatively aggressive clinical behavior and are known for their infrequent K-ras mutations. In this study, we investigated the methylation status of the RASSF1A promoter in association with 3p LOH and K-ras mutations in 48 flat colorectal tumors (39 early carcinomas and nine intramucosal high-grade dysplasias). RASSF1A hypermethylation was detected in 39 of 48 (81.3%) tumors and RASSF1A methylation was also detected in 19 of 39 (49%) normal colonic mucosal tissues. 3p21.3 LOH was detected in 20 of 42 (47.6%) cases, but RASSF1 methylation was detected in cases with LOH (14 cases) and retention of 3p21.3 (20 cases). K-ras mutations were detected in seven of 48 (14.6%) tumors and the concordant occurrence of K-ras mutation and RASSF1A methylation was detected in three of 48 cases (6.3%). Overall, there was a statistically significant mutually exclusive relationship between K-ras mutations and RASSF1A methylation. In conclusion, promoter hypermethylation of RASSF1A is a frequent event and may start early in the background normal mucosa in this tumor type. An alternative cascade of abnormalities in RAS transduction pathways may be responsible for the flat morphology and aggressive nature of flat colorectal neoplasms.

Usefulness of the [13C]‐urea breath test for detection of Helicobacter pylori infection in fasting patients

Most of the reported [13C]‐urea breath test procedures use a test meal, which is believed to assist in the spread of the [13C]‐urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum. Yet, procedures for the [13C]‐urea breath test and interpretation of the obtained 13C excess value have not been well established. We carried out the present study to validate the usefulness of the [13C]‐urea breath test in fasting subjects and to establish cut‐off values. [13C]‐Urea breath tests were performed on 258 Helicobacter pylori‐positive and 151 ‐negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [13C]‐urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta‐13C at the 20 min sampling point in H. pylori‐positive and ‐negative subjects was 31.0 ± 1.25 and 1.6 ± 0.11%o, respectively. Although the mean Δ13C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean Δ13C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut‐off value of 5.0%o is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [13C]‐urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.

Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients

Background : A decrease in pepsinogen and gastrin levels 1–3 months after Helicobacter pylori eradication is well known. However, few data are available on the long‐term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori‐negative patients with dyspepsia.