Histological estimation of the efficacy of endoscopic laser coagulation therapy for diffuse antral vascular ectasia.

We present the case of a 72-year-old woman with successful control of repeated episodes of bleeding from diffuse antral vascular ectasia (DAVE) by laser coagulation therapy. In addition to DAVE, the patient also suffered from severe iron deficiency anaemia (due to recurrent bleeding), liver cirrhosis, and huge tumours of hepatocellular carcinoma (HCC). She was referred from another hospital after failure to stop her bleeding episodes. Endoscopic examination revealed diffuse speckled telangiectasia over most of the stomach (from antrum to the upper portion of the body) and large numbers of blood clots. The patient had received repeated blood transfusions, haemostatic drugs, and H2 receptor antagonists at the other hospital, without improvement of the repeated bleeding. She underwent three sessions of endoscopic laser coagulation therapy for the lesions at our hospital after the final diagnosis of DAVE had been made based on the characteristic histological findings of biopsied specimens. This treatment improved her general condition and stopped the bleeding from the gastrointestinal tract even without fasting. Unfortunately, however, her liver function gradually worsened due to HCC and previous massive bleeding, and she finally died of liver failure three months after the last laser session. Autopsied specimens obtained from the patient's stomach revealed that macroscopic diffuse speckled telangiectasia and microscopic typical vasodilatation in mucosal and submucosal layers of gastric tissue had disappeared in the treated areas but not all portions of the DAVE lesion. These histological findings for the treated areas, in addition to the clinical improvement of bleeding, suggest that endoscopic laser coagulation therapy may be useful and one of the first choices in treatment for DAVE.

Oesophageal cavernous haemangioma diagnosed histologically, not by endoscopic procedures.

Haemangioma of the oesophagus is uncommon in patients with benign oesophageal tumours. We present a patient with an oesophageal haemangioma detected during mass screening of the upper gastrointestinal tract. The patient, a 59-year-old man, had neither abdominal complaints nor a history of gastrointestinal diseases. Endoscopic examination revealed a blue-coloured submucosal tumour (approximately 3 cm in diameter) at the middle portion of oesophagus. Endoscopic Doppler ultrasonography showed an homogeneous and hypoechoic mass without blood flow in the submucosal layer of the oesophagus. However, a magnetic resonance imaging scan did not give a typical image for oesophageal haemangioma. Therefore, partial resection of the tumour was performed to obtain a differential diagnosis using the procedures of endoscopic ligation and polypectomy. Histological examination of the resected tissue showed a cavernous haemangioma in the oesophagus. This endoscopic technique may be useful for the differential diagnosis of oesophageal haemangioma.

Complete regression of recurrent esophageal carcinoma with reduced expression of glutathione S-transferase-pi by treatment with continuous infusion of 5-fluorouracil and low-dose cisplatin infusion.

The mortality rate of recurrent esophageal carcinoma remains high because of its resistance to chemotherapy and radiation therapy. We present a patient with recurrent esophageal carcinoma, which dramatically disappeared after treatment with the combination of continuous infusion of 5-fluorouracil and low-dose cis-Diamminedichloroplatinum-II (cisplatin) infusion (FP therapy). Furthermore, we immunohistologically found that glutathione S-transferases (GST)-pi, a marker of resistance to cisplatin, was faintly expressed both in the endoscopical biopsy specimens of recurrent tumor and in the resected specimens of esophageal carcinoma and metastatic lymph nodes. FP therapy was suggested to be effective for recurrent esophageal carcinoma. Immunostaining for GST-pi might be a prospective marker for the sensitivity of esophageal carcinoma to FP therapy, particularly cisplatin.

Influence of rebamipide on indometacin-induced gastric hemorrhage in rats under restraint stress.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, CAS 11911-87-6) in preventing acute gastritis was examined in rats by stomach perfusion. Teprenone (CAS 6809-52-5), cimetidine (CAS 51481-61-9) and omeprazole (CAS 73590-58-6) were used as control drugs. Severe gastric hemorrhage was observed in conscious restrained rats, 1 h after treatment with indometacin (20 mg/kg i.p.). Pretreatment with rebamipide (3, 10 or 30 mg/kg s.c.) suppressed the hemorrhage induced by indometacin plus restraint stress, being more effective than teprenone or cimetidine. Pretreatment with omeprazole (30 mg/kg s.c.) did not suppress the gastric hemorrhage. Superoxide dismutase (30,000 U/kg s.c.) significantly decreased the hemorrhage. Anti-rat PMN (polymorphonuclear leukocytes), 1 ml/kg i.v., which caused depletion of circulating neutrophils, also suppressed the hemorrhage induced by indometacin plus restraint stress. Thus reactive oxygen species derived from neutrophils may play a role in the occurrence of the hemorrhage during acute gastritis induced by indometacin with restraint stress.

Inhibition by 16,16-dimethyl prostaglandin E2 of tumor necrosis factor-alpha and interleukin-1beta production and messenger RNA expression in human monocytes stimulated by Helicobacter pylori.

We investigated the effects of 16,16-dimethyl prostaglandin E2 on the production of tumor necrosis factor-alpha and interleukin-1beta in human monocytes stimulated with Helicobacter pylori. Monocytes isolated from human peripheral blood were incubated for 24 hr with the extract of H. pylori diluted 1:100 to 1:100,000 by volume, a combination of the extract and 16,16-dimethyl prostaglandin E2, or a vehicle alone. The extract stimulated the production of tumor necrosis factor-alpha and interleukin-1beta and the expression of their messenger RNA in a dose-dependent manner. 16,16-Dimethyl prostaglandin E2 inhibited the production of these cytokines and their messenger RNA in the presence of H. pylori at doses higher than 10(-6) M, predominantly with tumor necrosis factor-alpha. These data suggest that antiinflammatory effects of prostaglandins on gastric mucosa are in part related to their effects on inhibition of production of proinflammatory cytokines by monocytes.

Effect of culture conditions on morphological changes of Helicobacter pylori.

The morphological conversion of Helicobacter pylori from the spiral form to the coccoid form may be the expression of a transitory adaptation to an unsuitable environment. The mechanism(s) of this conversion are not clear. In this study, we examined whether the morphological conversion of H. pylori is affected by various culture conditions, such as oxygen concentration, pH, temperature, or the presence of beta-cyclodextrin. H. pylori (NTCC11916) was cultured on Brucella agar, followed by culture in Brucella broth containing 1% agar under several conditions. Morphological conversion of individual H. pylori on the agar plate was investigated with time after incubation under phase contrast microscopy. When H. pylori was inoculated in Brucella broth containing beta-cyclodextrin, the spiral form of the organism was observed even after 6 days of incubation under standard culture conditions: 37 degrees C, pH 7, and microaerobic atmosphere (5% O2/10% CO2/85% N2) (control). The morphological conversion of H. pylori was completed on day 3 in an aerobic atmosphere (20% O2 supply) and on day 2 in an undermicroaerobic atmosphere (<0.1% O2). Its complete morphological conversion was observed at pH 8 on day 5 and at pH 4 on day 6. All of the H. pylori (100%) incubated at 20 degrees or 42 degrees C had converted from the bacillary to the coccoid form on day 4. Conditioned medium without beta-cyclodextrin caused complete conversion on day 5. These results suggest that oxygen concentration, pH, temperature, and beta-cyclodextrin may be related to the H. pylori morphological conversion from the bacillary to the coccoid form.

Endoscopic resection of two granular cell tumours of the oesophagus.

Granular cell tumour of the oesophagus is rare and usually single. It is diagnosed by endoscopic appearance, results of endosonography, and histological examination of biopsy specimens. Although histological examination is required for diagnosis, it is difficult occasionally to obtain tumour samples by forceps because granular cell tumour is usually located in the submucosal layer. We report the case of a Japanese man with two granular cell tumours of the oesophagus. One lesion was diagnosed as a granular cell tumour by histological examination of a biopsy specimen, but the other was not. Endoscopic resection was performed to obtain the diagnosis and treat the lesions since some granular cell tumours are potentially malignant. Both tumours were completely resected endoscopically, and the diagnosis of granular cell tumour could be established by histological examination of resected tissue. Endoscopic resection is thus useful in the diagnosis and treatment of granular cell tumour of the oesophagus.

External pancreatic juice drainage through a percutaneous endoscopic drainage tube for the patient with a postoperative pancreatic juice leakage.

Percutaneous endoscopic gastrostomy (PEG) has been widely accepted for patients who have no swallowing ability but have an intact gut. Its clinical application is mainly for nutritional support and decompression of the intestine in patients with bowel obstruction. In this paper, we report external pancreatic juice drainage through a percutaneous endoscopic drainage tube in a patient with postoperative pancreatic juice leakage. Soon after this procedure, pancreatic juice leakage subsided. This procedure was minimally invasive for the patient and may be a new application of PEG to maintain the good quality of life (QOL) in a patient with pancreatic juice leakage.

Protective effect of rebamipide against ammonia-induced gastric mucosal lesions.

We investigated the protective effect of rebamipide against ammonia-induced gastric mucosal lesions. Participation of prostaglandin E2 and nitric oxide in the action of rebamipide was also examined. Rebamipide was administered intraperitoneally (10-100 mg/kg) to male Wistar/ST rats (150-325 g) fasted for 24 hr. Thirty minutes later, 1% NH4OH (1 ml) solution was given intragastrically. One hour later, the length of the mucosal lesions was measured (lesion index), and prostaglandin E2 (PGE2) was determined by radioimmunoassay. A 1% NH4OH solution caused gastric mucosal lesions with hemorrhagic necrosis and submucosal edema. PGE2 synthesis was not affected by NH4OH but was significantly increased by rebamipide. Rebamipide decreased the severity of NH4OH-induced gastric mucosal lesions in a dose-dependent manner. Pretreatment with indomethacin (5 mg/kg, subcutaneously) did not affect the protective effect of rebamipide; however, pretreatment with N(omega)-nitro-L-arginine (L-NNA, 1-10 mg/kg, intravenously), an inhibitor of nitric oxide synthase, attenuated the protective effect of rebamipide in a dose-dependent manner. Simultaneous administration of L-arginine (100 mg/kg) and L-NNA completely restored the protective effect of rebamipide, whereas D-arginine was inactive. These results suggest that nitric oxide contributes significantly to the protective effect of rebamipide against ammonia-induced gastric mucosal lesions.

Rebamipide prevents recurrence of gastric ulcers without affecting Helicobacter pylori status.

Rebamipide, a gastroprotective drug developed in Japan, accelerates ulcer healing and reduces recurrence of experimental gastric ulcers. We examined the effects of rebamipide, given during healing of human gastric ulcers infected with Helicobacter pylori, on the quality of ulcer healing and ulcer recurrence. Sixty H. pylori-positive patients with gastric ulcers were randomly allocated to three treatment groups: group O (N = 20) received 20 mg of omeprazole every day for eight weeks, group OR (N = 20) received the same dose of omeprazole and 300 mg of rebamipide three times a day for eight weeks, and group OA (N = 20) received the same dose of omeprazole for eight weeks and 1500 mg of amoxicillin three times a day for the first two weeks. After this treatment was completed no other medication was given. Endoscopic examinations were performed at the end of therapy (for healing rate), one month later (for rate of H. pylori eradication) and every three months for follow-up (for ulcer recurrence rate). At the end of therapy, biopsy specimens were taken from the gastric ulcer scar and examined under the microscope for neutrophil and mononuclear cell infiltration. The ulcer healing rate of the three groups was almost the same; H. pylori in group OA was 65% and that of the other two groups was 0%. The number of patients with a flat ulcer scar pattern (good quality of ulcer healing) was increased and the neutrophil infiltration was significantly improved in groups OR and OA compared to group O. The ulcer recurrence rate was significantly lower in group OA and group OR than in group O. In conclusion, rebamipide is almost equipotent to amoxicillin plus omeprazole for the reduction of ulcer recurrence. The decreased recurrence rate by rebamipide may be due to improvement of the quality of ulcer healing, reflected as in the suppression of inflammatory cell infiltration in the scar, which results from either cure of H. pylori infection and/or treatment with a gastroprotective drug such as rebamipide.

Increased mRNA levels of transforming growth factor-beta1 and monocyte chemoattractant protein-1 in ulcer relapse caused by interleukin-1beta in rats.

This study investigated the mRNA expression of transforming growth factor-beta1 (TGF-beta1) and monocyte chemoattractant protein-1 (MCP-1) in rat gastric tissues in which ulcers had relapsed due to interleukin-1beta (IL-1beta) administration. Rats with healed ulcers were administered IL-1beta (1 microg/kg) and killed after 0, 12, 24, or 48 hr. Both TGF-beta1 and MCP-1 mRNA levels were increased in the scarred gastric tissues at 24 hr (fourfold), when ulcers had not relapsed. Furthermore, the expression of these genes also increased in the ulcerated gastric tissues at 48 hr (fivefold), when 90% of healed ulcers had relapsed. On the other hand, the number of macrophages that had infiltrated the scarred gastric tissues at 24 hr was two times higher than that at 0 hr. At 48 hr, the number of macrophages that had infiltrated gastric tissues in which ulcers had relapsed was similar to that at 24 hr. Thus, TGF-beta1 and MCP-1 may be implicated in the macrophage infiltration, thereby leading to ulcer relapse due to IL-1beta.

Indomethacin treatment during initial period of acetic acid-induced rat gastric ulcer healing promotes persistent polymorphonuclear cell-infiltration and increases future ulcer recurrence. Possible mediation of prostaglandins.

The study was performed to examine whether indomethacin administered during the initial period of acetic acid-induced gastric ulcer healing affects future ulcer recurrence. Gastric ulcers were produced in rats by subserosal injection of acetic acid. Indomethacin (1 mg/kg/day, orally) administered either alone or concomitant with ornoprostil (50 micrograms/kg/day, orally) was started on the fourth day and continued for 56 days. In rats whose ulcer healed at the 90th day after production of ulcer, endoscopy was done every 30 days to examine recurrence of ulcer. Gastric specimens were obtained 10, 30, 60, 90, and 240 days after ulcer production for histology, to quantitate the height of regenerated mucosa, thickness of fibrous tissue, degree of polymorphonuclear cell infiltration, and PAS-positive cells. Cumulative ulcer recurrence rate was significantly higher in rats initially treated with indomethacin than in controls. Increased polymorphonuclear cell infiltration was the major histologic abnormality persisting after cessation of indomethacin. Ornoprostil reversed these abnormalities caused by indomethacin. In conclusion, the administration of indomethacin during the initial period of the ulcer healing promoted persistent polymorphonuclear cell infiltration and increased ulcer recurrence rates, possibly via a prostaglandin-dependent mechanism.