Twenty-nine patients operated on for colon cancer were preoperatively administered lentinan and recombinant interleukin-2 (rIL-2) in order to study the local immunomodulating effect on the tumor itself. The patients were divided into a control group, group A given 2mg of lentinan and 100, 000 JRU of rIL-2, and group B given 2mg of lentinan and 400, 000 JRU of rIL-2. Groups A and B received 8 doses of each agent from 2 weeks before the operation. Resected tumor tissues were subjected to immunostaining with antibodies for MT-1, CD4 or CD8. Greater local infiltration of CD4-positive T lymphocytes (p<0.05 in group B) and CD8-positive lymphocytes (p<0.05 in group B) was observed in groups A and B than in the control group. This infiltration increased along with the dose of rIL-2. When expression of the IL-2R β-chain was assessed after administration of lentinan and rIL-2, expression was even on the T lymphocytes infiltrating the interstitial around the cancers, and it was enhanced in group A and group B (p<0.05) compared with the controls. Both CD4- and CD8-positive cells expressed the IL-2R β-chain. This study indicated that IL-2R expression on lymphocytes was increased by concomitant administration of lentinan and rIL-2. These lymphocytes subsequently infiltrated tumors and mobilized effector cells.
The purpose of this study was to investigate the association between patients' prognosis and the discrepancy between macroscopic and pathological findings in gastric cancer. Consecutive 900 patients with gastric cancer who underwent resection for gastric cancer, were studied for the discrepancy between naked-eye and pathological findings of gastric cancers and for immunological makers, such as CD3 T, CD4 T cell, CD8 Tcell and immunosuppressive acidic protein (IAP). We demonstrated that patients whose tumors were both macroscopically and histologyically diagnosed early cancers showed significantly lower IAP levels than those whose tumors were macroscopically diagnosed adcanced, but histologyically diagnosed early cancers, and they also had better outcome than the other. In conclusion, surgeons' naked-eye determinations are very important to fight against gastric cancer, especially in patients with well differentiated adenocarcinoma, and moreover, patients who have more immunosuppressive conditions are tend to take misdiagnose.
Background: Although double staining of Victoria-blue (VB) with Hematoxylin-eosin (HE) is recommended to accurately evaluate cancer invasion to small veins, there are no reports with this method in invasive pancreatic duct cell adenocarcinoma. Methods: The resected specimens from 40 patients with invasive pancreatic duct cell cancer were stained with double staining of HE-VB to evaluate the relation of venous invasion and clinico-pathological factors or prognosis in comparison to HE staining alone. Results: Eighteen (45%) of 40 cases were positive for venous invasion in HE staining alone, whereas the positive rate increased to 31 (77.5%) of 40 cases in HE-VB double staining. In HE staining, significant differences were recognized only with nerve invasion and UICC stage, but a significant relationship to venous invasion was also recognized for histological type and lymph node metastasis in double staining. Regarding the relationship between survival rate and venous invasion with double staining, the survival rate in the negative group was significantly higher than that in the positive group. In univariate analysis using Cox's proportional hazard model, lymph node metastasis and venous invasion under double staining were significant prognostic factors. However, any factors were not significant in multivariate analysis. Conclusion: These results suggest that venous invasion with double staining can be a prognostic factor in pancreatic cancer, and it has statistically significant correlation with several other clinico-pathological factors.
To study the prognostic factors in patients with hepatic metastasis from colorectal cancer after hepatectomy and preventive arterial infusion chemotherapy (AIC). We examined outcomes in 42 patients treated with preventive AIC and evaluated possible prognostic factors by investigating clinicopathological variables with double staining with hematoxylin-eosin and Victoria blue for hepatic metastasis. The cumulative survival rates of patients with primary lesions smaller than 5cm were significantly greater than those of patients with primary lesions 5cm or larger in diameter. However, the site of primary lesion, Dukes' classification, and vessel invasion of the primary lesion did not affect survival. Although the cumulative survival rates of patients with vessel invasion in hepatic metastases were significantly lower than those of patients without vessel invasion, survival did not differ significantly on the basis of other variables. In addition, the incidence of recurrence was significantly higher in patients with vessel invasion of the primary lesion or lymph node metastasis than in other patients. These results suggest that vessel invasion of hepatic metastasis and that of primary lesions is significantly correlated with cumulative survival rates and recurrence in the remnant liver and strongly indicate an increased risk of recurrence.
Whether the hereditary cancer patients had survival advantage is a question that is still open for discussion. We suppose that the genes of cancer patients who have family histories are more diverse or polymorphic, or they are potentially more mutational than those without family history of cancer; consequently, these patients may have relatively good outcomes even if they are suffering from cancer. A consecutive series of 2880 Japanese cancer patients with a median follow-up of 2942 days was evaluated to know their outcomes and their family histories. Cancer patients with a positive family history have a five-fold increased risk of benign disease patients. Outcomes of cancer patients whose near relatives were suffering from cancer had better outcomes in especially females in first relatives. Outcomes of cancer patients whose parents were suffering from cancer had better than the other groups. Our results establish the correlation between cancer family history and outcome, resulting good outcomes following good treatment for cancer and that potentially important genetic information that key genes which correlate a long-life may be located on X chromosome.
Chemotherapy administered to a case of non-resectable advanced gastric cancer with esophageal invasion and bone metastasis was found to be remarkably effective over two years and 4 months. For imaging investigation, the efficacy of the chemotherapy was judged to be a partial response (PR), Furthermore, DNA histograms prepared by flow cytometry as a diagnostic test for malignancy of cancer revealed changes in the primary lesion from an aneuploidy pattern to a diploidy pattern concomitant with the administration of chemotherapy. Since non-phasic metastasis to the cerebellum and the adrenals were detected subsequently, intensive therapy consisting of radical gastric resection, left adrenal resection and deep cerebellur nucleus resection combined with radiotherapy, was conducted with the objective of prolonging the survival of the patient.The total course extended for about 4 years and considering the stage of advanced cancer, we believe that a favorable quality of life (QOL) was achieved based on the Performance status (P. S) level, maintenance of a satisfactory level of meal consumption, continuation of employment at times other than hospital admission and a home-residence rate of 72.3 per cent.
We performed HLA typing in order to clarify the association. between the cancer risk, the patients' outcome, and the phenomenon of over-dominant selection (heterozygote advantage) at the major histocompatibility complex (MHC) in Japanese cancer patients. The subjects consisted of 3219 Japanese individuals (2275 male and 944 female), 2776 of whom had several types of cancers that were confirmed pathologically by means of resected or biopsied specimens, 318 who had benign diseases, and 125 normal control subjects. HLA antigens were serologically tested using the NIH standard microlymphocytotoxicity method for HLA-A, B, C, DR and DQ antigens. Eight HLA-A antigens, 20 HLA-B antigens, 5 HLA-C antigens, 12 HLA-DR antigens, and 4 HLA-DQ antigens were examined. Cancer subjects showed a significant lower frequency of human leukocyte antigen-A33 (11.5% vs. 15.6%; P=0.0152; relative risk (RR)=0.7062), B44 (10.8% vs. 14.2%; P=0.0328; RR=0.7281), and DR9 (26.9% vs. 31.8%; P=0.0302; RR=0.7871) than noncancer subjects, respectively. They also showed a significant lower frequency in heterozygote patients who had all detectable and different forms of antigens at HLA-A, -B, -C, -DR, and -DQ loci than in non-cancer subjects, having 8.4%, and 15.8%, respectively (p<0.00001, RR=0.4882). But patients who had heterozygote advantage at MHC did not show good outcomes. Our data strongly suggest that individuals with heterozygous or homozygous alleles at HLA class I and II are more resistant to cancer, have more susceptibility to cancer, respectively, but with no effect on their outcomes.
To confirm that the genes of the Japanese are more homozygous in terms of MHC than those of people in other countries, we evaluated the data concerning HLA antigens from the 11th HLA Conference and those from our own study. This study consisted of 4, 166 Japanese and 7, 717 non-Japanese who were examined for HLA antigens. The incidence of heterozygotes at all HLA class I and II loci in Japanese and in non-Japanese was 103% and 24.0%, respectively, whereas that of homozygotes was 40.5% and 27.5%, respectively. Our results led to the conclusion that Japanese individuals are more homozygous than foreigners, resulting in different incidences of both benign and malignant diseases, different responses to both medical and surgical therapy, and different immune responses to viral and bacterial infection. For that reason, social prevention and individualized therapy is important in Japanese medical care.
An investigation was retrospectively made regarding the lateral lymph node dissection in 96 cases of lower rectal cancer excised at the Tokyo Medical University Hospital between 1989 and 1998. Lateral lymph node dissection was performed in cases of invasion to the proper tunica muscularis recti or deeper and in cases of metastasis to the lymph nodes surrounding the rectum or beyond (that is, metastasis to lymph nodes farther than the rectum periphery). Lateral lymph node metastasis was recognized in 8 of 31 cases (25.8%) making up the dissection group, and in these cases, upward lymph node metastasis was at n1 or above and invasion was a1 or beyond. Local recurrence was found in 12 of 31 cases (38.7%) with lateral lymph node dissection and in 12 of 65 cases (18.6%) with no lateral lymph node dissection (control group). In a comparison with the control group by the Kaplan-Meier method, the disease-free survival rate was significantly lower in the dissection group. In a multivariate analysis by Cox's proportional hazard model, lymph node metastasis (p=0.022) was found to correlate with prognosis, but no significant correlation with lateral lymph node dissection was manifested.