Shu Hirai

Impact of rabeprazole, a new proton pump inhibitor, in triple therapy for Helicobacter pylori infection—comparison with omeprazole and lansoprazole

: A recent trend in curative therapy for Helicobacter pylori infection is the so‐called triple therapy, which consists of a proton pump inhibitor (PPI) and two different antimicrobials. Various regimens employing this triple therapy have been reported. However, little is known about the effectiveness of rabeprazole, a recently developed proton pump inhibitor, when used in the triple therapy.

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.

Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis.

BackgroundThe esophageal tight junction is responsible for the paracellular sealing of the epithelium. Alteration of the expression of tight-junction proteins plays crucial roles in the pathogenesis of some human diseases. The aim of this study was to investigate the distribution and expression pattern of tight-junction proteins in the esophageal mucosa of control rats and rats with reflux esophagitis.MethodsChronic acid reflux esophagitis was experimentally induced by operation in rats. The animals were killed on days 7 and 14 after the operation. The thickness of the mucosa and the 5-bromo-2-deoxyuridine (BrdU) labeling index were assessed. The expression pattern of the tight-junction proteins claudin 1-4 and occludin in the esophageal mucosa was investigated by immunofluorescence staining and Western blotting in the controls and esophagitis rats.ResultsIn the esophagitis model, the thickness and BrdU labeling index increased with time. In control rats, claudin-1, -3, and -4 were localized on the cellular membranes of esophageal epithelial cells, mainly in the spinous and granular layers, while claudin-2 was not detected in any layer. Occludin was seen on the cellular membranes in all esophageal mucosal layers. In the esophagitis rats, the expression of claudin-1 was increased both in the plasma membrane and in the cytoplasm around the erosion in the spinous and granular layers. The expression of claudin-4 and occludin shifted to the cytoplasm from the plasma membrane in the spinous and granular layers. In contrast, the expression of claudin-3 was decreased in the spinous and granular layers.ConclusionsThe localization and the expression patterns of tight-junction proteins were different in the controls and the rat esophagitis model. The expression of claudin-3 in the esophageal mucosa was decreased, while that of claudin-1 was increased. It is postulated that these alterations in tight-junction proteins most likely increase the permeability of the esophageal the epithelium, thereby impairing the defense mechanism of this epithelium.

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.

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.

Improvement of gastric atrophy after Helicobacter pylori eradication therapy.

AbstractBackground:It remains controversial whether gastric atrophy is reversible after Helicobacter pylori eradication therapy.Aim:To clarify whether gastric atrophy improves after H. pylori eradication therapy using a histologic approach.Methods:Subjects were 87 H. pylori infection-cured patients

Breast carcinoma diverging to aberrant melanocytic differentiation: a case report with histopathologic and loss of heterozygosity analyses.

A case of primary breast cancer showing differentiation to malignant melanoma is reported. To obtain insight into the clonal relationship between the two components of the tumor, polymerase chain reaction-based microsatellite analysis to detect loss of heterozygosity on chromosome arms 1p, 1q, 3q, 4q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, 17q, and 18q with microdissected tissues of both components was performed in addition to histologic, histochemical, immunohistochemical, and ultrastructural techniques. The tumor consisted of a combination of carcinoma and melanoma with morphologic transition. Metastases in the lymph nodes and thoracic spinal bone marrow showed dual tissue structure. One of the metastatic lung tumors showed melanomatous tissue structure. The abundant pigment in the cells was positive for Fontana-Masson staining and bleached with potassium permanganate. The carcinoma component was positive for epithelial membrane antigen and CA19-9, but the melanoma component was negative. Conversely, the melanoma component was positive for HMB45 and vimentin, but the carcinoma component was negative. Electron microscopic analysis showed premelanosomes and melanosomes in the melanoma component. Microsatellite analysis showed the same genetic alterations with loss of heterozygosity on chromosome arms 1p, 3q, 4q, 6q, 9p, 10q, 11q, 13q, 16q, 17p, and 17q in in situ, invasive, and metastatic foci. We concluded that the carcinoma and melanoma components had arisen from the same clone and that this breast carcinoma might have diverged to aberrant malignant melanoma through multiple genetic alterations in the early period of ductal carcinoma in situ.

Carcinosarcoma of the esophagus characterized by myoepithelial and ductal differentiations

We report a case of carcinosarcoma of the esophagus characterized by ductal and myoepithelial differentiation. A 61‐year‐old man was operated on for a polypoid tumor of the distal esophagus. Histologically, this tumor was composed of ductal structures and sarcomatous spindle cells surrounding the ducts at the central area of the tumor. The tumor was also composed of squamous cell and basaloid carcinoma in the periphery. Immunohistochemically, a few spindle cells surrounding the ductal structures showed immunopositivity for α‐smooth muscle actin and S‐100 protein. Electron microscopy revealed that the spindle cells had tonofilament and pinocytic vesicles in the cytoplasm, and basal lamina adjacent to the cytoplasmic membrane. Both of the results strongly supported the suggestion that the spindle cells may be myoepithelial cells. Basaloid carcinoma showed a gradual transition to chondrosarcomatous cells producing the matrix, which had both immunopositivities for S‐100 protein and cytokeratin. Therefore, chondrosarcomatous cells may be derived from carcinoma cells. The histogenesis of this tumor may be associated with a totipotential stem cell of esophageal mucosa, which has the potential to differentiate into squamous cells, ductal cells or myoepithelial cells.

Pleomorphic adenoma in nasal cavity: immunohistochemical study of three cases

Intranasal pleomorphic adenoma is a rare neoplasm, and thus only one case report addressed immunohistochemical findings of this neoplasm. To define immunohistochemical features of intranasal pleomorphic adenoma, we studied three cases of the pleomorphic adenoma developed from the nasal septum. Subsequently, immunohistochemical reactivities of the tumor cells for various cytokeratins, glial fibrillary acidic protein (GFAP), S100 protein, alpha-smooth muscle actin (SMA), and vimentin were similar to those of pleomorphic adenoma of the parotid gland. The tumors examined in this study had different histological components, such as predominance of myxoid area, solid area, or tubuloductal structure, but immunoreactivity of both epithelial and myoepithelial tumor cells were the same in the tumors. Therefore, immunoreactivity of the tumor cells were the same among the intranasal pleomorphic adenoma having various histological components.