Teruyuki Kishida

High dose probiotic and prebiotic cotherapy for remission induction of active Crohn's disease

Background:  Clinical trials of probiotic treatment for Crohn’s disease (CD) have yielded conflicting results. This study assessed the clinical usefulness of combined probiotic and prebiotic therapy in the treatment of active CD.

Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans

BACKGROUND Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. AIMS To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. PATIENTS AND METHODS Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n=9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n=45) and H pylori negative healthy subjects (n=15). COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. RESULTS COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. CONCLUSIONS Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylorirelated gastritis, suggesting its involvement in the tissue repair process.

Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa.

OBJECTIVES:One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori.METHODS:Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and 13C-urea breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm2 of the lamina propria mucosa.RESULTS:There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy.CONCLUSIONS:These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.

Helicobacter pylori infection increases the risk of colorectal adenoma and adenocarcinoma, especially in women

BackgroundRecent reports suggest that Helicobacter pylori infection can potentially increase the risk of colorectal cancer. The purpose of this study was to assess the association between H. pylori infection and the risk of colorectal adenoma and adenocarcinoma, and to evaluate any differences on the basis of sex.MethodsThe subjects were 669 (40- to 80-year-old) patients who underwent both barium enema examination and total colonoscopy, and who were evaluated for H. pylori infection by 13C-urea breath test, urease test, or histological diagnosis of biopsied gastric specimens. There were 142 H. pylori-negative and 527-positive patients. The odds ratios (ORs) for H. pylori-positive patients with colorectal adenoma and adenocarcinoma, and for tumor patients with either adenoma or adenocarcinoma were calculated.ResultsAmong the H. pylori-negative patients, there were 52 patients without tumor, 63 with adenoma, 27 with adenocarcinoma, and 90 with tumor. Among the H. pylori-positive patients, there were 136, 264, 127, and 391 patients respectively. Pooling all subjects, those infected with H. pylori had a significantly increased OR for adenoma, adenocarcinoma, or tumor, compared to H. pylori-free patients (OR, 1.60, 1.80, and 1.66, respectively). For female H. pylori-positive subjects, the risk of having adenocarcinoma or tumor was significantly higher than that for their H. pylori-free counterparts, while for male H. pylori-positive and -negative subjects, there was no such significant difference.ConclusionsThe results therefore suggest that, in patients aged 40–80 years, H. pylori infection increased the risk of colorectal adenoma and adenocarcinoma, with significantly higher risks for female patients.

Monocyte chemoattractant protein 1 and macrophage cyclooxygenase 2 expression in colonic adenoma.

Background and aims: Cyclooxygenase 2 (COX-2) expression in subepithelial macrophages of colorectal adenoma has been suggested as the first in a series of steps leading to colorectal tumorigenesis. We tested the hypothesis that chemokines released from human colorectal adenoma epithelium might be involved in COX-2 expression in macrophages of the lamina propria. Methods: Endoscopic samples of sporadic colorectal adenomas were tested by enzyme linked immunosorbent assay for chemokines involved in macrophage chemotaxis. Localisation of adenoma macrophage chemoattractant protein 1 (MCP-1) and COX-2 were determined by immunohistochemistry. The effects of MCP-1, in the presence or absence of celecoxib, on COX-2 expression, and prostaglandin (PG) E2 and vascular endothelial growth factor (VEGF) release, were examined in human macrophages isolated from peripheral blood. Results: MCP-1 levels were markedly higher in adenoma with mild-moderate dysplasia (129.7 (19.9) pg/mg protein) and severe dysplasia (227.9 (35.4) pg/mg protein) than in normal colonic mucosa (55.8 (4.2) pg/mg protein). Other chemokine levels, macrophage inflammatory proteins (MIP)-1α and MIP-1β, and the chemokine regulated on activation of normal T cell expressed and secreted (RANTES) did not vary significantly between adenoma and normal mucosa. MCP-1 levels in both adenoma and normal colonic mucosa increased significantly three hours after tissue cultivation in vitro. MCP-1 immunoreactivity was restricted to the adenoma epithelium, with no reactivity seen in adjacent normal epithelial cells. MCP-1 stimulated COX-2 expression and PGE2 and VEGF release in human macrophages. Celecoxib, a selective COX-2 inhibitor, inhibited MCP-1-induced PGE2 and VEGF release in macrophages. Addition of exogenous PGE2 reversed this inhibitory effect on VEGF release, suggesting that MCP-1 in adenoma epithelial cells might be involved in COX-2 expression and subsequent macrophage activation. Conclusions: MCP-1 in colorectal adenoma epithelial cells might be involved in macrophage migration and COX-2 expression, leading to the subsequent development of colonic adenoma.

Analysis of bile acids in colon residual liquid or fecal material in patients with colorectal neoplasia and control subjects

Bile acids are believed to play a role in the etiology of colorectal cancer. To examine the relationship between bile acids and colorectal neoplasia, bile acids in colon residual liquid or fecal material were analyzed in 18 patients with colorectal adenoma, 12 patients with colorectal cancer, and 18 healthy control subjects. High-performance liquid chromatography combined with immobilized 3α-hydroxysteroid dehydrogenase in column form showed a significant evevation in the proportion of deoxycholic acid (P<0.05), lithocholic acid (P<0.05), secondary bile acids (deoxycholic acid plus lithocholic acid) (P<0.02), and the chenodeoxycholic acid-lithocholic acid family (chenodeoxycholic acid plus lithocholic acid) (P<0.05) in the colon residual liquid or fecal material of the patients with colorectal adenoma compared with proportions in the control subjects. A similar trend was noted in the patients with colorectal cancer compared to the control subjects. These findings suggested that an increase in the proportion of secondary bile acids, in particular, of lithocholic acid, was closely related to the pathogenesis of colorectal neoplasia.

Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer

Abstract: We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3 cm than in those with a tumor ≤3 cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor.

Clinical significance of serum iron and ferritin in patients with colorectal cancer

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 ± 38.6μg/dl vs 93.0 ± 32.1 μg/dl and 107.1 ± 32.9μg/dl, respectively (p < 0.001). The mean value of serum ferritin levels in patients with early and advanced colorectal cancer was also significantly decreased compared with controls, 80.5 ± 35.0ng/ml (p < 0.01) and 48.8 ± 72.8 ng/ml (p < 0.001), respectively, vs 117.1 ± 46.8 ng/ml. However, there was no significant difference between mean serum iron levels in patients with early colorectal cancer and controls. Eighteen (78.3%) of the 23 patients with advanced colorectal cancer and 3 (16.7%) of the 18 patients with early colorectal cancer had serum iron levels below 85μg/dl and serum ferritin levels below 60ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.

Significance of Serum Iron and Ferritin in Patients with Colorectal Adenomas

BACKGROUND Colorectal adenomas are often detected on mass screening, although detection rates with fecal occult blood tests are low. The relationship between colorectal adenomas and the resulting blood loss was examined indirectly, using serum iron and ferritin levels. METHODS Serum iron and ferritin concentrations were measured in 184 men with colorectal adenomas (> or = 1 cm in 92; < 1 cm in 92) and in 92 healthy male controls. Values in the three groups were compared. In the patients with adenomas > or = 1 cm, serum iron and ferritin levels were compared on the basis of the site, number, histology, and degree of dysplasia of the adenoma. RESULTS The mean serum iron level was significantly lower in patients with adenomas > or = 1 cm than in controls (P < 0.05), although this level did not differ significantly between those with adenomas < 1 cm and controls. The mean serum ferritin level also was significantly lower in patients with adenomas > or = 1 cm than in those with adenomas < 1 cm and controls (P < 0.05, P < 0.01, respectively), although this level did not differ between those with adenomas < 1 cm and controls. There was no difference in mean serum iron or ferritin levels on the basis of the site, number, histology, or degree of dysplasia of the adenoma. CONCLUSIONS We conclude that decreased serum iron and ferritin levels are related only to adenoma size and that adenomas > or = 1 cm may bleed steadily, resulting in iron deficiency. However, low dietary intake of iron and fiber may be one of the causes of low serum iron and ferritin.

Influence of alcohol consumption on the association between serum lipids and colorectal adenomas.

Background: There have been no reports that low serum cholesterol levels increase the risk of colorectal adenoma, although many studies have shown that they do increase the risk of colorectal cancer. Alcohol intake, which is associated with a risk of colorectal adenomas, and serum cholesterol levels are closely related. The purpose of this study was to evaluate the influence of alcohol consumption on the association between serum cholesterol levels and colorectal adenoma. Methods: The subjects were 1,349 male patients who underwent both barium enema examination and total colonoscopy. They answered a questionnaire regarding their alcohol consumption history, and their blood samples were analysed. The subjects were divided into three groups: those with no tumour (with neither adenoma nor adenocarcinoma), those with adenoma and those with adenocarcinoma. Among the groups, the serum total cholesterol and triglyceride levels were compared in all the patients, in the patients who did not drink daily and in the patients who did. Results: In all the patients, the serum cholesterol and triglyceride levels did not differ between the patients with and those without adenoma. In the daily drinkers, the serum cholesterol and triglyceride levels were significantly lower in patients with adenoma than in those without. Conclusions: Significantly lower levels of serum cholesterol and triglycerides were found in daily drinkers with adenoma than in those without.