This article describes the progress and the problems of QOL studies in the West, the development of QOL questionnaires in Japan, and studies performed using such questionnaires. In general, the same method of assessing QOL used in the West could be employed in Japan, but problems with the acceptability of the QOL questionnaires, the way of evaluating overall QOL, and the influence of information on the diagnosis of cancer were picked up. The QOL studies performed in Japan provide some answers to these problems in this review.
The expression of Lewisx and sialyl-Lewisx antigens was investigated immunohistochemically in 24 patients with intrahepatic cholangiocarcinoma. Seventeen cholangiocarcinomas of the hepatic hilum (hilar tumors) and 7 peripheral cholangiocellular carcinomas (peripheral tumors) were studied, as well as 9 normal livers obtained at autopsy. Staining of cancer cells for Lewisx and sialyl-Lewisx antigens was classified into 4 categories: negative [type N], membranous or cytoplasmic with polarity [type P(+)], membranous or cytoplasmic without polarity [type P(-)], and stromal [type S]. The 24 cancers were also divided into HLA-DR-positive and -negative lesions. In the 9 normal livers, Lewisx was expressed by the peribiliary glands in 6 cases, but was not expressed by the bile duct epithelium in any case. Type N staining for Lewisx was prevalent in hilar intrahepatic cholangiocarcinoma, while HLA-DR-negative tumors were more often type N or P(+) than HLA-DR-positive tumors. Among the patients with hilar tumors, those with type P(-) or S staining had a better 5-year survival rate than those with type N or P(+) staining, although the difference was not statistically significant. In contrast, there was no difference in sialyl-Lewisx expression between the peribiliary glands and the bile duct epithelium. No trend in the distribution of sialyl-Lewisx staining was found, and patients with type P(-) and S hilar tumors had a similar 5-year survival rate to those with type N and P(+) staining. These results suggest that the Lewisx staining pattern of tumor cells may contribute to determination of the origin of intrahepatic cholangiocarcinoma.
In the interest of developing more effective adoptive immunotherapy, we investigated the effect of cyclophosphamide (Cy) on the induction of tumor-specific cytotoxic T lymphocytes (CTL). When co-cultured with autologous tumor cells, patient peripheral blood mononuclear cells (PBMC) developed the ability to kill either autologous or HLA class I-matched allogeneic tumor cells. This killer activity was completely blocked by pretreatment with an anti-CD3 monoclonal antibody (MAb) plus complement. The CTL activity of PBMC from Cy-treated patients was compared with the activity of cells obtained from the same patients before Cy treatment. It was found that Cy treatment greatly enhanced patient' CTL activity (from 15.9±1.1 to 26.5±1.1% in patient 1 and from 7.6±2.3 to 28.7±2.3% in patient 2: both P<0.001). We also found the same phenomenon in vitro, since addition of Cy at the initiation of stimulator and effector cultures resulted in enhanced CTL activity. However, addition of Cy after the generation of CTL did not increase CTL activity, suggesting that Cy acts on the induction phase, but not the effector phase of CTL. Thus, our results indicate that Cy can enhance CTL activity and suggest that administration of Cy together with CTL injection may be helpful in developing new forms of adoptive immunotherapy.
At present, chemoterapy still achieves poor results in advanced pancreatic cancer and sometimes the patient's quality is impaired by useless chemotherapy. To improve this situation, we used the nuclear damage assay (NDA) as a chemosensitivity test for pancreatic cancer. We performed the NDA on percutaneous needle biopsy tissue obtained from 19 patients with inoperable advanced pancreatic cancer, and 16 of them were successfully assayed by the chemosensitivity test. We could get a positive response to the assay in 13 of the 16 patients. The 13 patients with a positive response were treated with the agent selected by the NDA, while 3 patients with no response were treated with 5FU. The outcome of chemotherapy was a complete response in one patient, no change in 5, and progressive disease in 7 of the patients showing tumor sensitivity in the assay. On the other hand, only progressive disease was found in the patients with no response in the assay. The survival rate of the former group was better than the latter (P<0.05), and the median survival time was 23.4 and 11.1 weeks, respectively. We also report in detail the patient with a complete response to VP-16, which is rarely effective against pancreatic cancer. These results suggest that NDA of percutaneous needle biopsy tissue might improve the efficacy of chemotherapy for advanced pancreatic cancer.
The number of argyrophilic nucleolar organiser regions (AgNOR) per cell reflects the biological aggressiveness of tumors, but the prognostic significance of AgNOR has not been elucidated, yet. In this study, we investigated 157 patients with breast cancer, nine with fibroadenoma, nine with sclerosing adenosis and 15 with normal breast tissue using an AgNOR staining technique. The AgNOR score was significantly higher in breast cancer tissue than in both normal breast tissue and benign lesions (P<0.001). The AgNOR score had a relationship with both the tumor size and lymph node status of breast cancer (P<0.001 and P<0.005, respectively). The relapse-free survival of patients with a high AgNOR score (_??_3.95, mean value) was significantly worse than that of patients with a low AgNOR score (<3.95) (P<0.05). However, multivariate analysis showed that the AgNOR score was not an independent prognostic indicator for breast cancer. In conclusion, the AgNOR score reflects tumor aggressiveness and it may be a useful prognostic indicator in breast cancer patients for whom other prognostic information is unavailable.
Assessment of malignant potential by indentifying argyrophilic nucleoplar organizer regions (AgNORs) and immunostaining expression for CA19-9 was carried out in 50 human gastric cancers. The AgNORs count was significantly lower in early gastric cancer than in advanced gastric cancer. The AgNORs was correlated significantly with the macroscopic stage, the depth of invasion, peritoneal dissemination, and lymph node metastasis. Positive immunoreactivity for CA19-9 was found in 33 (66.0%) of the 50 gastric cancers. Tumors with strong immunostaining for CA19-9 had a significantly (P<0.05) higher AgNORs count than those with negative or weak immunostaining. The difference in survival time between the AgNORs count group (n=28, AgNORs count: <6.48) and the high AgNORs count group (n=22, AgNORs count: >6.48) was statistically significant (P<0.01). These results suggest that evaluation of cellular kinetics using AgNORs gives important prognostic information, and that tumor cells with a high using AgNORs have the ability to produce high levels of CA19-9.
We have previously presented results suggesting that HLA antigen status could predict the response of cancer to therapy, and have proposed that rational individualized therapy for cancer patients might possibly be designed by evaluating HLA antigens. In this study, we classified gastric cancer patients into four groups using quantification method III and then developed a simple method of classifying patients to HLA antigen status for easy clinical application.
We retrospectively evaluated the efficacy of postoperative adjuvant therapy in 541 gastric cancer patients who underwent gastrectomy. Postoperative adjuvant chemotherapy consisted of the intravenous injection of MMC and/or the oral administration of fluoropyrimidines, while immunochemotherapy was done by adding the oral administration of PSK. The overall survival rate (Kaplan-Meier method) was improved by postoperative adjuvant therapy. However, there was no significant difference in survival between the patients receiving chemotherapy and those receiving PSK. Cox multivariate regression analysis of the factors related to survival (including sex, age, tumor size, pTNM stage, histological grade and therapy) indicated that postoperative therapy was a significant prognostic factor. The age and sex of patients receiving chemotherapy were also significant prognostic factors, but this was not so far patients receiving chemotherapy plus PSK. Patients given chemotherapy plus PSK showed a better relative survival rate than those receiving only chemotherapy. We conclude that postoperative adjuvant chemotherapy and immunochemotherapy may give better results than gastrectomy alone, and that the age of the patients needs to be considered before postoperative adjuvant chemotherapy started.