Satoshi Hase

Carcinoid tumors of the gastrointestinal tract: evaluation with endoscopic ultrasonography

To evaluate the usefulness of endoscopic ultrasonography for carcinoid tumors, we examined 29 patients with gastrointestinal carcinoid tumors (5 gastric, 7 duodenal, and 17 rectal). The smallest size detectable by endoscopic ultrasonography was 2 mm in diameter histologically. The cross-sectional image of the tumors was primarily oval to round. The internal echo was generally hypoechoic and homogeneous. The margins were clearly visualized, and the contour was somewhat smooth. The tumors were mainly located in the third layer. The second layer covered the tumor with the third layer at its base, and it abutted the tumor and became indistinct near its upper interface. These findings were especially recognized in lesions with submucosal invasion and were similar at all sites. The overall accuracy of determining the depth of invasion using endoscopic ultrasonography was 75% (27 of 36 lesions). Limited to the lesions detectable by endoscopic ultrasonography, the accuracy was 90%. Endoscopic ultrasonography was useful in determining the presence of local metastases. Moreover, endoscopic ultrasonography allowed direct detection of perigastrointestinal lymph node metastases (75%, three of four patients). In conclusion, endoscopic ultrasonography was found to be useful for the staging of gastrointestinal carcinoid tumors by determining depth of involvement and presence of perigastrointestinal lymph node metastases.

Effects of Prednisolone and Human Epidermal Growth Factor on Angiogenesis in Granulation Tissue of Gastric Ulcer Induced by Acetic Acid

In an attempt to elucidate the role of granulation vessels in the healing of gastric ulcer, healing and angiogenesis in granulation tissue of acetic acid ulcers were studied in rats. In addition, the effects of prednisolone and synthetic human epidermal growth factor (EGF) on angiogenesis and ulcer healing were investigated. The newly formed granulation vessels in the ulcer base were measured by means of a carmine dye infusion method. Prednisolone, administered subcutaneously at 40 mg/kg/day, significantly decreased angiogenesis in the ulcer base on the 10th day after ulcer production, and on the 30th day ulcer healing was found to be significantly delayed. In contrast, angiogenesis was significantly increased, and ulcer healing was enhanced by intragastric administration of 100 micrograms/kg/day of EGF. With combined administration of prednisolone and EGF, angiogenesis was significantly increased compared to that observed with prednisolone treatment alone. The authors conclude that suppression of angiogenesis by prednisolone is a delaying factor in gastric ulcer healing and that exogenous EGF promotes ulcer healing, partly through restoration of angiogenesis.

Effects of Cimetidine and Omeprazole on Angiogenesis in Granulation Tissue of Acetic Acid-Induced Gastric Ulcers in Rats

We investigated the effects of cimetidine and omeprazole on angiogenesis in granulation tissue and on the healing of gastric ulcers induced by acetic acid in rats. Either cimetidine (50 or 100 mg/kg) or omeprazole (10 or 20 mg/kg) was orally administered once daily for 9 consecutive days from the day following ulcer production. The ulcer index on the 10th and 30th days after ulcer production, and the extent of angiogenesis on the 10th day were examined. Cimetidine dose-dependently decreased the extent of angiogenesis on the 10th day, whereas the ulcer index on the 10th days was not significantly different between cimetidine-treated and control rats. The ulcer index of the groups treated with cimetidine during the initial 9-day period was increased compared with the control group on the 30th day. In contrast, oral omeprazole did not affect angiogenesis on the 10th day and decreased the ulcer index on both the 10th and 30th days. These results suggest that oral cimetidine may inhibit angiogenesis in ulcer granulation tissue possibly via the blocking of histamine H2 receptors and this may be one cause of delayed ulcer healing.

Three-Dimensional Endoscopic Ultrasonography of Gastrointestinal Lesions Using an Ultrasound Probe

BACKGROUND This study was carried out to ascertain the clinical usefulness and problems of three-dimensional (3D) images obtained with the ultrasound probe. METHODS Eighteen resected specimens and 21 patients were examined. After the images were recorded on video, 3D displays were produced using a workstation. RESULTS In the in vitro study the surface images were quite consistent with the macroscopic findings in 17 cases. In 2 esophageal cancers, 7 of 10 gastric cancers, and 2 colonic cancers the depth of tumor invasion was assessed accurately from the reconstructed images. In the in vivo study although 3 D display had some limitations, it was useful in esophageal and rectal lesions. CONCLUSIONS This new diagnostic method could visualize the 3D extent of gastrointestinal lesions and appears to have a useful clinical application.

A new method for evaluating gastric ulcer healing by endoscopic ultrasonography

We observed the quantitative estimation of the transmural changes associated with gastric ulcer healing by using endoscopic ultrasonography (EUS). It was possible to diagnose the depth of ulcer by EUS. Forty-eight patients were divided into three treatment groups. Group A (n = 16) was treated with 800 mg cimetidine daily, group B (n = 22) with 20 mg omeprazole daily, and group C (n = 10) with 400 mg cimetidine + 300 mg gefarnate daily. EUS was performed before and after 2, 4, and 8 weeks of treatment. The groups were compared from the viewpoints of endoscopic findings and contraction rate of the length and the cross-sectional area of the ulcer in EUS pictures. The best healing of both the endoscopic and EUS findings was seen in group B. By estimating the changes inside the ulcer, EUS may provide useful information for choice of anti-ulcer agents.

Relationship between local immune response to Helicobacter pylori and the diversity of disease : investigation of H. pylori-specific IgA in gastric juice

In order to evaluate the relationship between local immune response to Helicobacter pylori and the diversity of disease, 77 asymptomatic subjects who underwent a health examination were studied. Helicobacter pylori‐specific IgG in serum and H. pylori‐specific IgA in gastric juice were measured by ELISA, and the measured IgA titre was classified into two grades, low or high. Histological classification of gastritis was performed according to the Sydney system. Cytokines in gastric juice were also measured, and the cytotoxin‐associated gene A (cagA) status of H. pylori was tested by PCR. Of the 65 subjects who were positive for H. pylori‐specific IgG in serum, 38 (58.5%) were classified as H. pylori‐specific IgA low titre in gastric juice and 27 (41.5%) had high titres. In the IgG‐positive, IgA‐low group, the rate of peptic ulcers (especially duodenal ulcers) in endoscopic findings was higher (P < 0.05); the score of activity and the density of H. pylori were higher (P < 0.001 and P < 0.05, respectively); the score of metaplasia was lower (P < 0.05); and the level of interleukin‐1β was lower (P < 0.05) than in the IgG‐positive, IgA‐high group. The positive rate of the cagA gene was 84.4% and there was no significant difference between the two groups. There were differences in endoscopic and histological findings between the IgG‐positive, IgA‐low and the IgG‐positive, IgA‐high groups. It is suggested that persons infected with H. pylori can be divided into two different states of disease according to local immune response.

The Role of H2 Receptors in Gastric Mucosal Blood Flow

To determine the relation between H2 receptors and gastric mucosal blood flow, we measured the latter in rats by the electrolytically generated hydrogen gas clearance technique. The blood flow increased significantly after intravenous injection of 0.1 mg/kg of impromidine, a very potent and specific agonist of H2 receptors. On the other hand, gastric mucosal blood flow decreased significantly after intravenous administration of 5 or 20 mg/kg of cimetidine or 2 mg/kg of famotidine. However, 2 or 20 rng/kg of omeprazole, whose anti-secretory effect is as strong as that of H2 blockers such as cimetidine and famotidine, caused no significant change in the gastric rnucosal blood flow. This indicates that H2 receptors regulate gastric mucosal blood flow in rats.

Effect of omeprazole on gastric acid secretion in rat: Evaluation of dose, duration of effect, and route of administration

SummaryThe effect of omeprazole on gastric acid output was studied in rats before and during stimulation by continuous administration of tetragastrin at 50 Μg/kghour. From 5 to 20 mg/kg of omeprazole was given to animals intraperitoneally, perorally and intravenously from 2 to 24 hours before the gastric secretory study was started, and the respective effects on acid secretion were compared. In each administration group, 20 mg/kg of omeprazole was the most potent among the groups receiving 5, 10 or 20 mg/kg, when the drug was given 2 hours before the study. There were statistically significant differences between the control group given tetragastrin only and each of the groups given 20 mg/kg of omeprazole perorally, intraperitoneally and intravenously. There was no significant difference among the groups given 20 mg/kg of omeprazole intraperitoneally, intravenously and perorally. The effect of 20 mg/kg of omeprazole continued at least 24 hours after the agent was administered perorally.

Effects of Histamine H2-Receptor Antagonists and a Proton Pump Inhibitor on the Mucosal Hydroxyproline Content of Ethanol-HCI-lnduced Gastric Lesions in Rats

We evaluated the effects of different antisecretory agents (H2-receptor antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH-HCl). The lesion indices showed the highest value 30 min after administration of EtOH-HCl and a significantly decreased value 15 h later. The mucosal hydroxyproline concentration was significantly increased 30 min after EtOH-HCl administration, reached a maximum 6 h later and subsequently decreased as time passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not reduce the lesion indices in less than 24 h and suppressed the increase in mucosal hydroxyproline concentrations significantly compared with the control group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal hydroxyproline concentrations. These facts suggest that H2-receptor antagonists might delay the healing of EtOH-HCl-induced gastric lesions through the suppression of collagen regeneration under the condition of exclusion of gastric acid secretion.

Short report: effect of sucralfate on angiogenesis in granulation tissue of acetic acid‐induced gastric ulcers in rats

We investigated the effect of sucralfate on angiogenesis in granulation tissue of gastric ulcers induced by acetic acid in rats using the carmine dye method. Intragastric administration of sucralfate at a dose of 500 mg/kg twice daily for 9 days significantly accelerated ulcer healing and significantly increased the extent of angiogenesis in the ulcer base on the tenth day after ulcer induction. As we reported previously, intragastric administration of cimetidine at a dose of 100 mg/kg once daily for 9 days decreased the extent of angiogenesis on the tenth day. However, combination treatment using sucralfate and cimetidine accelerated ulcer healing significantly, without altering the extent of angiogenesis. It is concluded, therefore, that the treatment with sucralfate may be effective in peptic ulcer disease from the standpoint of angiogenesis in the ulcer base.