Takashi Sakagami

COVERED WALLSTENT FOR PALLIATION OF MALIGNANT COMMON BILE DUCT STRICTURE: PROSPECTIVE MULTICENTER EVALUATION

Background:  Occlusion due to tumor ingrowth is a major drawback in self‐expandable metallic stents. Covering the stent is a probable solution to prevent tumor ingrowth. A manufactured covered self‐expandable metallic stent, Covered Wallstent, has become commercially available. We evaluated the Covered Wallstent in a prospective uncontrolled multicenter setting.

Influence of Helicobacter pylori infection on development of stress-induced gastric mucosal injury.

Abstract: Immediately after the Great Hanshin Earthquake in Kobe in 1995, the recurrence rate of peptic ulcer in patients infected with Helicobacter pylori was higher than that in patients in whom H. pylori had been eradicated. We evaluated the influence of H. pylori infection on stress-induced gastric mucosal injury in Mongolian gerbils and C57BL/6 mice. These animals were immersed in water for 30, 120, and 720 min 12 weeks after inoculation with H. pylori, and then killed to assess gastric mucosal damage, and to measure cytokine production (interleukin [IL]-1β, IL-4, IL-6, and IL-10; interferon [IFN]-γ; and tumor necrosis factor [TNF]-α) in the gastric tissue of the mice. The stress treatment for 30 min resulted in a significantly higher bleeding rate and bleeding index among infected gerbils and mice compared with results in uninfected animals. Conversely, the bleeding and ulcer indexes were significantly higher in uninfected gerbils after 720 min of the stress treatment than in infected gerbils. Prior to the stress treatment, gastric IL-1β and IFN-γ production was significantly higher in the infected group than in the uninfected group. After 120 min of the stress treatment, TNF-α production was increased in the infected group, and IL-1β and IL-10 production was increased in the uninfected group. However, the production of these cytokines showed no change at 30 min of the stress treatment. These results suggest that H. pylori infection influences the development of gastric mucosal injury in the early phase of stress exposure; cytokines do not play a major role in this process.

Helicobacter pylori Does Not Promote N-Methyl-N-nitrosourea-induced Gastric Carcinogenesis in SPF C57BL/6 Mice

Helicobacter pylori (H. pylori) infection has been acknowledged as a promoter and an initiator for gastric carcinogenesis in experimental models using Mongolian gerbils with H. pylori strains TN2GF4 and ATCC 43504, which have +ve cagA and vacA phenotype s1/ml. To get more insight into the role of H. pylori in gastric carcinogenesis, we studied the effect of H. pylori SS1, which has +ve cagA and vacA phenotype s2/m2, on Af‐methyl‐N‐nitrosourea (MNU)‐induced chemical gastric carcinogenesis using SPF C57BL/6 mice. Thus, H. pylori SSI was inoculated 1 week after the completion of MNU treatment to examine the promoting effect of this bacterium. The incidences of polypoid lesions, differentiated adenocarcinomas, and adenomatous hyperplasias were 67% (10/ 15), 47% (7/15) and 80% (12/15), respectively, in the MNU‐alone group. The corresponding figures were 31% (8/26), 23% (6/26) and 35% (9/26) in the MNU+H. pylori group. The incidences of polypoid lesions and adenomatous hyperplasia were significantly different between the groups. Thus, the results indicate that H. pylori SSI infection reduced susceptibility to chemical gastric carcinogenesis in this model. The discrepancy between the present result and previous results is likely to have been caused by differences in host factors and bacterial factors. Further study of the relationship between gastric carcinogenesis and H. pylori infection is needed.

Role of bacterial strain diversity of Helicobacter pylori in gastric carcinogenesis induced by N-methyl-N-nitrosourea in Mongolian gerbils.

Aim:  Helicobacter pylori is known to enhance gastric carcinogenesis induced by chemical carcinogens. We previously demonstrated that infection with H. pylori strain SS1 did not enhance such carcinogenesis in C57BL/6 mice. Whether this result was due to the bacterial strain SS1 or to the experimental host, C57BL/6 mice, should be addressed. Therefore, we examined whether H. pylori strains introduced to the same host (Mongolian gerbils) differed in carcinogenicity.

Disappearance of rectal mucosa-associated lymphoid tissue lymphoma following antibiotic therapy.

Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal B-cell neoplasm occurring most frequently in the stomach. The majority of gastric MALT lymphomas regress after Helicobacter pylorieradication therapy, and its development is considered to be closely associated with H. pylori infection. A few recent studies have reported on such regression of rectal MALT lymphoma after H. pylori eradication therapy (1–3). We report a case of rectal MALT lymphoma in whichH. pylori eradication therapy had no effect, but lymphoma disappeared under single antibiotic therapy.

Successful eradication of Helicobacter pylori prevents relapse of peptic ulcer disease

The NIH consensus conference in 1994 recommended that all patients with peptic ulcers should be tested and treated for Helicobacter pylori. Recent studies have shown that the eradication of H. pylori is associated with a significant reduction in the relapse rate of peptic ulcers, but there are few reports about long‐term outcome.

Pathologic changes in the glandular stomach and duodenum in an H. pylori-infected Mongolian gerbil model.

We have established a Helicobacter pylori-infected Mongolian gerbil model following Hirayamas method to investigate gastric diseases associated with H. pylori infection. We orally administered the culture broth of H. pylori ATCC 43504 to 8-week-old male Mongolian gerbils. After this, the gerbils were fed in a vinyl isolator. Subsequently, over the course of 48 weeks some of them were sacrificed for histopathologic examination and H. pylori culture. H. pylori colonization in the glandular stomach was seen in all the infected gerbils but only a few H. pylori were detected histologically. Acute inflammation, immature epithelium, and erosion were observed 2 weeks after H. pylori infection. Chronic inflammation was noted from 4 weeks after H. pylori infection. In addition, we found intestinal metaplasia and gastric ulcers from 12 and 24 weeks, respectively. There was mild to moderate inflammation in the duodenum but no ulcerative lesions or gastric metaplasia were observed. Some histologic findings were similar to those in humans, but inflammation occurred mainly in the deep mucosa and submucosa. This is a good animal model for H. pylori-associated gastric diseases but not for duodenal ulcers or gastric metaplasia. It might be useful for investigating the pathogenesis of H. pylori infection in the stomach.

Phase I study of paclitaxel plus irinotecan combination therapy for patients with refractory and advanced gastric cancer: PHASE I STUDY OF PACLITAXEL/IRINOTECAN FOR GASTRIC CANCER

No adequate second‐line chemotherapy regimen for advanced gastric cancer is available.

Mongolian Gerbils Model

Since the isolation of Helicobacter pylori (H. pylori),much clinical and experimental effort has been spent on this bacterium to clarify the relationship with gastroduodenal disorder. The results, especially in the clinical field, have led to the recognition of H. pylori as a causal pathogen of gastroduodenal diseases, such as gastritis and peptic ulcer. Statements of management for peptic ulcer related to H. pylori infection were issued worldwide.1,2 The International Agency for Research on Cancer (IARC), a working group of WHO, acknowledged H. pylori as a definite carcinogen of gastric cancer (Group 1 carcinogen) in 1994.3 What needs to be emphasized at this juncture is that this decision was based on epidemiological data alone. Little was known about animal experimental data for gastric carcinogenesis related to H. pylori. The scarceness in animal data was explained by the lack of appropriate animal models of H. pylori infection. However, we have seen drastic changes. An appropriate animal model to investigate H. pylori infection was established in 1996 in Japan. Hirayama et al established an animal model infected with H. pylori using Mongolian gerbils.4 In this model, H. pylori infection persisted over a long term and caused gastric lesions. In addition, the processes of gastric mucosal changes resembled those of humans. In this chapter, we examine the serial changes in gastric lesions including gastric carcinogenesis in this model.