The epidemiological evidence linking Helicobacter pylori infection to gastric carcinogenesis is reviewed. Only large geographical population studies have revealed a positive correlation between H. pylori infection and the incidence or mortality of gastric cancer.
In cace-control studies, the correlation varied in high-risk and low-risk countries, depending on the prevalence of H. pylori antibodies in the control group. In high-risk countries for gastric cancer, gastric atrophy is common in both the patient and control groups, and intestinal metaplasia is associated with a decrease of serum H. pylori antibody positivity. Both of these factors may be related to the negative correlation between gastric cancer and H. pylori infection.
In cohort studies, a significant positive correlation has been revealed between H. pylori infection and the risk of gastric cancer. Direct evidence on the progression of gastric atrophy in H. pylori-infected animal models and indirect evidence in clinical studies has been accumulated. H. pylori infection may be linked to gastric carcinogenesis via atrophy and intestinal metaplasia of the gastric mucosa, which accelerates cell proliferation and the exposure of epithelial cells to endogenous and exogenous mutagens. In addition, the secretion of ascorbic acid (anti-oxidant) into gastric juice is decreased.
As the WHO/IARC recently defined H. pylori as a group 1 carcinogen for gastric cancer based on these epidemiological studies, patients with H. pylori infection must be considered a high risk group for this cancer.

抄録全体を表示

Cytotoxic T lymphocytes (CTL) were induced from the peripheral blood mononuclear cells of 6 cancer patients using tumor necrosis factor-α (TNF α). Initially, TNF α (100 and 1, 000U/ml) was added at the beginning of mixed culture with tumor lymphocytes for 3 days. Then, TNF α was removed and the cells were stimulated with an immobilized anti-CD3 monoclonal antibody (1μg/ml) and interleukin-2 (1, 000U/ml) for 3-7 days.
Subsequently, the anti-CD3 antibody was removed, and the cells were incubated with 500U/ml of interleukin-2. Cells from 2 patients showed autologous tumor-killing activity before incubation with TNF α, and this activity was unchanged by TNF α. In 2 of the 4 patients without pre-existing cytotoxic T lymphocyte (CTL) activity, there was an increase of this activity after incubation with TNF α. Both CTL activity and CTL proliferation increased in accordance with the TNF α concentration.
Flow cytometric analysis revealed an increase of CD8+Leu15- cells. However, the increase in cytotoxic activity also occurred when allogeneic cancer cells were identified as target cells, suggesting that TNF α did not increase tumor specificity although it increased autologous tumor-killing acitivity. Since a high CTL activity specific to autologous tumor cells is necessary for successful CTL therapy, this subject requires further investigation.

抄録全体を表示

A case of breast cancer that was only detected by contact thermography is presented. The 50-year-old patient had no distinct breast tumor and had only multiple indurations of the left breast. Mammography revealed no tumor. However, thermography showed a prominent pattern of abnormal hyperthermic vessels and a hyperthermic region in the upper inner quadrant of the breast. Biopsy of this region revealed an invasive ductal carcinoma which was 0.8cm in maximum diameter. Contact thermography appears useful for detecting early breast cancer.

抄録全体を表示

We examined the effects of a biological response modifier, lentinan, on tumor-infiltrating lymphocytes in advanced colon cancer. The subjects were 57 curatively resected patients with Dukes' B or C colon cancer, which was histologically diagnosed as well differentiated or moderately differentiated adenocarcinoma. The control group (n=29) did not receive any preoperative treatment. In the lentinan-treated group, lentinan was administered intravenously at 2 weeks and 1 week before surgery at a dose of 2mg (n=10), 4mg (n=8), or 8mg (n=10) each time.
The number of tumor-infiltrating lymphocytes increased depending on the dose of lentinan, and there was a significant difference between the control group and the patients given 4mg or 8mg of lentinan (P<0.05). Comparison of the subsets of tumor-infiltrating lymphocytes showed no difference in CD4⁺ cells between the groups. However, CD8⁺ cells showed a dose-dependent increase with lentinan treatment and there was a significant difference between the control group and patients given 8mg of lentinan (P<0.05). In addition, the number of emperipoletic lymphocytes detected by light microscopy at all lentinan doses was significantly higher than in the control group (P<0.05). Emperipoletic lymphocytes were mainly CD8⁺ T cells, but a few were CD4⁺, with the latter being almost all detected around ducts lined with cancer cells. The emperipoletic CD8⁺ cells were confirmed to be cytotoxic T lymphocytes by double staining with CD8 and CD11b.
When cytotoxic T lymphocytes, natural killer cells, and other killer cells attack cancer cells, they must make contact with the tumor cell membrane. Detection of emperipoletic lymphocytes at the light microscopic level means that these lymphocytes are in contact with the cell membrane or have penetrated into cancer cells.
Therefore, the finding that emperipolesis was significantly enhanced by lentinan supports the role of killer cells in the antitumor effect of this agent.

抄録全体を表示

To examine whether HLA status is one of the genetic factors influencing the incidence of gastric cancer, we determined HLA-DPB1 and -DRB1 types in 186 Japanese gastric cancer patients by DNA typing. It was found that DPB1^*0901 was significantly more common in the patients than in a control group (relative risk=1.86, P<0.003, corrected P<0.05). DRB1^*1502 was also more common in the patients than in the controls (relative risk=1.72, P<0.006), but the corrected P value (<0.15) indicated no statistical significance. When DPB1^*0901 and DRB1^*1502 were investigated as the DPB1^*0901-DRB1^*1502 haplotype, it was also found to be significantly more common in the cancer patients than in the controls (P<0.003).
These results suggest that the DPB1^*0901-DRB1^*1502 haplotype-related gene is associated with a high incidence of gastric cancer in the Japanese population.

抄録全体を表示

Objective: To compare the pattern of recurrence and the survival rate after two regimens of adjuvant chemotherapy following curative resection of gastric cancer.
Design: Prospective multicentre trial.
Setting: Twenty-one departments of surgery.
Subjects: A total of 163 patients who had undergone histological curative resection.
Interventions: All patients received an intravenous bolus of mitomycin C (20mg) on the day of operation, and a dose of 10mg on the first postoperative day. They were then randomized to receive either oral tegafur (600mg/day) or tegafur-uracil (600mg/day) for 2 years from 2 weeks after the operation.
Main outcome measures: The pattern of recurrence and the survival rate were assessed.
Results: Tegafur-uracil reduced peritoneal recurrence when compared with tegafur. About 70% of all patients had recurrece within two years. The tegafur-uracil group had a significantly higher 7-year survival rate than the tegafur group (P=0.04).
Conclusion: The overall recurrence rate was generally lower in the tegafur-uracil group, although there was no statistical difference. Most of patients had recurrence occurred within 2 years after surgery. This finding indicates that postoperative maintenance therapy for 2 years is necessary to suppress recurrence.

抄録全体を表示

This study was conducted to determine the value of DNA ploidy and the Ki-67 labeling index as prognostic indicators in 102 patients with gastric carcinoma.
No significant differences of the DNA ploidy pattern were observed in relation to sex, age, lymph node metastasis, serosal invasion, or tumor stage. However, the ploidy varied depending on tumor differentiation. The Ki-67 labeling index was closely associated with lymph node metastasis, serosal invasion, and tumor stage. In addition, patients with diploid tumors or a low Ki-67 labeling index had a better prognosis.
These findings suggest that both the DNA ploidy pattern and the Ki-67 labeling index might be good prognostic indicators for gastric carcinoma.

抄録全体を表示

In the present study, an immunohistochemical investigation of neuron-specific enolase (NSE), a specific neural isomer of the widely distributed glycolytic enzyme 2-phospho-D-glycerate hydolase, was carried out in the pancreatic tissue of 41 patients with ductal carcinoma of the pancreas. We also measured nuclear DNA content by means of static cytometry (SCM) using a CAS 200 Image Analysis System (Cell Analysis System, Inc., Lombard, IL.) and evaluated the parameters associated with nuclear DNA content such as the DNA ploidy pattern, DNA index (D. I) and 4c exceeding rate (4c ER) in the pancreatic tissues of 41 patients. Then, we studied the relationship between immunohistochemcal expression of NSE and DNA content of tumor cells in pancreatic cancer.
Immunoreactivity for NSE was observed in 21 of the 41 ductal carcinomas (51.2%), and the incidence of NSE positivity was higher in tubular adenocarcinoma. The DNA index and 4c ER in the NSE positive patients were higher than those in the patients with negative immunoreactivity for NSE (DNA index: 1.80±0.70 vs. 1.58±0.69; 4c ER: 20.40±11.68 vs. 13.17±8.09). The differences in DNA index and 4c ER between these groups suggested that neoplastic cells expressing NSE had a higher malignant potential.
In conclusion, the NSE immunoreactivity of pancreatic ductal carcinoma may directly reflect the malignant potential of neoplastic cells represented by DNA content and may be a useful prognostic parameter.

抄録全体を表示

The AgNOR count is closely related to cell proliferative activity and analysis of the DNA content by image or flow cytometry is a reliable method of predicting the prognosis of patients with various cancers. In the present study, we retrospectively examined the relationship between the AgNOR count and the DNA content in 14 patients (7 males and 7 females) with surgically resected using paraffin-embedded sections. The AgNOR count and AgNOR area were examined by a silver staining technique and the mean nuclear AgNOR count or area for at least 200 tumor cells in each specimen was calculated using the CAS 200 Image Analysis System (Cell Analysis System, Inc., Lombard, IL). DNA analysis, all specimens were done using the Quantitative Ploidy Analysis Program in the CAS 200 Image Analysis System.
The DNA ploidy pattern and diploid rate (2c rate) of 200 tumor cells were calculated and the percentage of cells with an aneuploid nuclear DNA content over 4c (4c+rate) was also calculated.
The AgNOR count and tumor cell area of aneuploid tumors were significantly (P<0.05) higher than those of diploid tumors. In addition, there was a relationship between the AgNOR count and the 4c+rate.
In conclusion, analysis of the DNA ploidy and AgNOR parameters may provide important prognostic information in bile duct cancer.

抄録全体を表示