Alimentary Pharmacology & Therapeutics Symposium Series最新文献

Summary

Background

Accumulating evidence, outlined in this review, at last provides some elucidation of the orgin of gastrointestinal epithelial tumours.

Methods

New techniques, such as following the process of crypt or gastric gland purification following mutation in genes encoded by the mitochondrial genome, have shown that mutations spead within the proliferative unit, either gastric gland or intestinal crypt, by clonal purification or monoclonal conversion. Spreading otside the crypt or gland then takes place by fission.

Results

Future research should focus on the mecanisim by which mutated stem cells colonize crypts, and on the mechanisms of crypt fission itself.

Summary

Background and Aims

The immune system is a major determinant of the pathophysiological inflammation, which may lead to gastrointestinal mucosal injury in patients with Crohn's disease. Cytokines such as tumour necrosis factor-alpha are well-known mediators of the immune system, and treatment with a chimeric anti-tumour necrosis factor-alpha antibody (infliximab) has been shown to be highly effective in patients with Crohn's disease. Recent evidence indicates that infliximab induces apoptosis in lamina propria T lymphocytes in these patients. To better understand the mechanisms of infliximab's effect on gastrointestinal inflammation, we investigated changes in the serum level of cytokines after treatment in these patients, and the effect of infliximab in inducing the apoptosis of T lymphocytes.

Methods

Thirteen patients with Crohn's disease were treated with infliximab at a dosage of 5-mg/kg body weight. Clinical response was evaluated using the Crohn's Disease Activity Index, and serum soluble interleukin-2 receptor, interleukin-6, tumour necrosis factor-alpha levels were analysed by enzyme-linked immunosorbent assay at 0 and 2 weeks after treatment. Apoptosis of peripheral and lamina propria T lymphocytes after culture with infliximab was detected by flow cytometry.

Results

Crohn's Disease Activity Index decreased in 12 of 13 patients, and serum soluble interleukin-2 receptor, interleukin-6 and tumour necrosis factor-alpha levels decreased in most patients after treatment with infliximab. Tumour necrosis factor-alpha level before treatment in the six patients in whom Crohn's Disease Activity Index decreased by more than 70 was <5 ng/mL. Infliximab induced the apoptosis of lamina propria but not of peripheral T lymphocytes.

Conclusion

These findings suggest that a low level of serum tumour necrosis factor-alpha is an indicator for infliximab treatment. The induction of apoptosis of lamina propria T lymphocytes by infliximab may be an important mechanism of its anti-inflammatory effect in patients with Crohn's disease.

Summary

Background

Levels of pepsinogen have been reported to correlate with the degree of gastric atrophy in Helicobacter pylori-infected gastric mucosa.

Aim

To investigate the relationship between PG levels and histological atrophy before and after H. pylori eradication.

Methods

Eradication therapy was conducted on 180 H. pylori-positive patients with upper gastrointestinal conditions. Endoscopy was performed prior to and at 2, 12 and 24 months after successful eradication therapy. Histological findings were scored using the updated Sydney System in the antrum and the corpus of the stomach. Pepsinogen was measured.

Results

Pepsinogen I levels dropped significantly at 2 months after the eradication. By 12 months and 24 months post-eradication they had risen again. Histological improvement was seen in atrophy at all sites at 24 months after the eradication. A significant correlation between atrophy and pepsinogen I was seen from prior to eradication. The correlation coefficient was greater at 2 months post-eradication, decreased again at 12 months and was no longer significant at 24 months.

Conclusions

Our results suggest that pepsinogen levels correlate with the degree of gastric mucosal atrophy prior to and soon after successful eradication therapy, but that the degree of correlation subsequently declines over time.

Summary

Background

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

Aims

To determine the safety and optimal dose of paclitaxel/irinotecan as a second-line chemotherapy for patients with advanced and recurrent gastric cancer.

Patients and methods

Sixteen patients with refractory and advanced measurable gastric cancer who were resistant to 5-FU plus cis-diamminedichloroplatinum (CDDP) therapy (FP) were enrolled. Paclitaxel/irinotecan was given intravenously on days 1, 8, and 15 in repeated 4-week cycles. Paclitaxel/irinotecan doses were escalated in a stepwise fashion as follows: 50/40 mg/m², 50/50 mg/m², 50/60 mg/m², 60/60 mg/m², 60/70 mg/m² in levels I, II, III, IV and V, respectively.

Results

Because of one patient with Grade 3 febrile neutropenia at level I, three more patients were enrolled in level I. Doses were consequently escalated, and in level IV, Grade 3 febrile neutropenia occurred in one patient. Since an additional patient in level IV had grade 4 neutropenia, Level IV was judged as the maximum tolerated dose (MTD). The recommended dose and schedule for phase II study is paclitaxel 50 mg/m² and irinotecan 60 mg/m² on days 1, 8, and 15 every 4 weeks. Partial response was observed in 4 of 16 patients.

Conclusion

Paclitaxel/irinotecan combination regimen at the level III dosage was safe and well tolerated.

Summary

Background

Recent evidence suggests that Helicobacter pylori infection is involved in the pathogenesis of extra-gastrointestinal diseases such as coronary heart disease.

Aim

To determine the association of H. pylori infection with biochemical parameters of atherosclerosis in the serum.

Methods

One hundred and fifty-nine patients with H. pylori-positive peptic ulcer (duodenal ulcer, n=89; gastric ulcer, n=70) receiving triple therapy were studied prospectively for up to 3 years for clinical parameters associated with inflammation and cardiovascular events. Blood was tested at the time of annual check-up.

Results

Eradication was successful in 137 patients (86%), and body weight, body mass index (BMI) and TG levels increased gradually each year. No significant hanges were seen in plasma levels of total cholesterol, interleukin-6 or interleukin-8, whereas those of HDL-C increased significantly, and those of C-reactive protein, fibrinogen and LDL-C decreased.

Conclusion

There is evidence for the possible implication of H. pylori infection in the etiology of cardiovascular events via its exacerbation of or influence on risk factors of atherogenesis.

Summary

Background

Degranulated mast cells may be missed by histochemical and immunohistological techniques, making the histological assessment of activated mast cells difficult.

Aim

To use a novel mast cell surface antigen 1 (MASA-1) to detect activated mast cells.

Methods

Surgical samples of human intestine were obtained from 15 patients with ulcerative colitis (UC), 14 patients with Crohn's disease (CD) and 11 controls. Frozen sections were cut and MASA-1 was detected and quantified by enzyme immunohistology. Immunohistological double staining with anti-MASA-1 and either anti-CD68 or anti-c-Kit antibody was also performed.

Results

The number of MASA-1-positive cells was significantly higher in the submucosal layer and muscularis propria in patients with CD than in patients with UC or controls. The number of MASA-1-positive cells was significantly higher in the muscularis propria in patients with UC in highly inflamed colon compared with controls and less inflamed colon. Human intestinal MASA-1-positive cells are not from the macrophage lineage and showed heterogeneous expression of c-Kit.

Conclusion

The increased number of mast cells in the submucosa and muscularis propria in patients with CD suggests that the involvement of activated mast cells in transmural inflammatory responses possibly including tissue remodelling.

Summary

Background

Twelve years has passed since we introduced laparoscopic surgery for gastroduodenal perforation.

Aim

To list problems and to investigate the feasibility of our clinical protocol for treatment of gastroduodenal ulcer perforation.

Methods

Case records of 62 patients and histology samples of 9 patients undergoing surgery for gastroduodenal perforation were retrospectively reviewed.

Results

Laparoscopic omental implantation is feasible for some cases of perforated peptic ulcer in patients who have either stenosis or massive perforations. In patients undergoing laparoscopic omental implantation, oral ingestion of water was started at 3.3 ± 0.5 post-operative days. Helicobacter pylori was positive in 27 of 35 patients (77%). Of 22 cases in whom intraoperative ascitic culture was taken, Candida was positive in nine (41%), and in six of eight cases involving wound infection or intraperitoneal abscess. Histological examination of resected stomach revealed the fungi with hypha formation at the base of the ulcer in 44% of patients.

Conclusions

Laparoscopic omental implantation was more feasible than in the past. The possibility of Candida infection and subsequent abscess formation must be considered in patients with gastroduodenal ulcer perforation.

Summary

Background

Effects of long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) on the colon have not been well characterized.

Aim

To investigate colonoscopic findings and prevalence of adverse events following long-term use of NSAIDs.

Methods

The study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age- and sex-matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre-endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics.

Results

The occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1-30 years (mean 7.8). Nine of 13 patients (69.2%) took low-dose aspirin.

Conclusion

The prevalence of colonic lesions in long-term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non-NSAIDs users. The most common features of NSAIDs-associated colitis were segmental ischeznia.