Temperature elevation to 42°C to 45°C can lethally damage bacterial and mammalian cells. Recently, clinical interest in hyperthermia as a cancer treatment modality has prompted many in vitro and in vivo basic science studies designed to elucidate the mechanisms responsible for the antitumor effect of exposure to elevated temperatures. Mechanisms for thermal damage are not clear, although effects on the cell membrane and nucleus occur in association with heat exposure. In recent years it has become clear that lipid peroxidation due to free radicals is involved in a variety of different types of cell injury and that the effective use of cell injury can be applied to cancer therapy. We used a rabbit model to investigate the role of various radical scavengers and the degree of lipid peroxidation in the tumor tissue during the antitumor effect of hyperthermia. These observations suggest that injury to the cell membrane and intracellular organelle membrane due to lipid peroxidation may be involved in the antitumor effect of hyperthermia. The objectives of this review are, first, to discuss some of the roles of reactive oxygen species in pathopysiological conditions; and, second, to summarize results from animal experiments that lipid peroxidation mediated by reactive oxygen species plays an important role in the antitumor effect of hyperthermia.
No useful tumor makers for renal cell carcinoma (RCC) have yet been established. In the present study, the serum IAP level was assessed sa a diagnostic and follow-up marker for RCC. The subject were 16 women and 52 men with RCC (28-87 years old) and 30 healthy adult controls (20-68 years old). Serum IAP levels were assayed by the single radial immunodiffusion method and the cut-off level was set at 500μg/ml. The IAP level was significantly higher in the RCC than in the controls. The IAP positivity rate was 63.2% in the RCC patients Patients and 16.7% in the controls. Elevation of IAP was related to clinical stage. The IAP Positivity rate was 83.9% in patients with high stage RCC and 35.1% in those with low stage RCC. The prognosis of low stage RCC with IAP level over 1, 000μg/ml was quite poor. In contrast, even high stage patients with IAP levels of 500μg/ml or less had a longer survival compared with those having elevated IAP levels. Additionally, in the low stage patients, the IAP level decreased significantly after radical nephrectomy compared with that at diagnosis. Patients with the IAP levels of 500μg/ml or less after nephrectomy also had a longer survival than those with the levels over 500μg/ml. Based on these results, it was concluded that IAP may be auseful marker for RCC, although it appears valuable for assessing the prognosis than for diagnosis. A more accurate assessment of the prognosis of RCC was possible using a combination of the IAP value and clinical stage.
A rare cese of secretory carcinoma of the breast diagnosed by aspiration cytology is reported. A 55-year-old woman was referred to our hospital with a small mass in the right breast. Aspiration cyology revealed a characteristic "bunch of grapes" appearance and modified radical mastectomy was performed. Histrogic examination of the resected mass demonstrated tumor cells forming glandular structures with eosinophilic fluid in the lumens. Both the fluid and the cytoplasm of the tumor cells were positive for PAS and alcian blue stains. From these findings, the lesion was diagnosed to be a secretory carcinoma of the breast. Secretory carcinoma of the breast can be diagnosed by aspiration cytolpgy, when the characteristic "bunch of grapes" appearance is recoginized.
The doubling time carcinoembryonic antigen level (CEA doubling time) and the clinico-pathological factors contributing to the increase in CEA were investigated in 46 previously untreated patients with recurrent pulmonary adenocarcinoma. The CEA doubling time was found to show a wide variation, ranging from 13 to 168 days, with a mean of 64.8±47.1 days (mean±SD) and a median of 47 days. The CEA doubling time did not differ significantly between male and female patients. However, the CEA doubling time was significantly shorter in patients under 60 years old compared with older patients. It was also significantly shorter in patients with poorly differentiated adenocarcinoma than in those with well or moderately differentiated adenocarcinoma. Furthermore, the CEA doubling was significantly shorter in patients with brain metastasis than in those with metastasis to other organs (bone, lung, and cervical lymph nodes). This findings is compatible with the clinical observation that cerebral lesions generally develop relatively soon after surgery for pulmonary adenocarcinoma.
A 68-year-old Japanese woman with locally recurrent gastric adenocarcinoma was treated by FLP (cisplatin, 5FU, and leucovorin) therapy. On March 8, 1990, she underwent total gastrectomy for gastric adenocarcinoma, which was stage II (N1 S1 P0 H0) by the Japanese classification and Stage II (T2 N1 M0) by the American classification. She was given 5FU (150mg/day). Postoperarively, in May 1992, she complained of food sticking in her epigastrium. On June 29, fiberscopic examination revealed an ulcer opposite the jejunal anastomosis as well as stenosis. Biopsy of the jejunal mucosa showed group V changes. On August 11, she was admitted to our center with locally recurrent gastric adenocacinoma and impared food intake. She received parenteral nutrition and gradually improved. In September, she received intravenous FLP therapy twice. During this therapy, transient nausea and diarrhea developed. Fiberscopic examination was performed twice after the completion of treatment and revealed healing of the ulcer to a scar with stenosis. Biopsy of the jejunl mucosa showed no malignancy. The patient underwent operation and no malignancy was detected, suggesting that the recurrent, tumor was cured.
We evaluated the effect of immunotherapy using OK-432 in 67 gastric cancer patients with peritonitis carcinomatosis and investigated markers predicting the response to immunotherapy. All patients were followed up until death. The study enrolled 67 patients with biopsy-proved adenocarcinoma of the stomach associated with peritonitis carcinomatosis, of whom 56 underwent operation and 29 underwent gastrectomy. Seven were inoperative and 4 had recurrence with ascites due to peritonitis carcinomatosis. They were randomly assigned to receive chemotherapy with or without a streptococcal biological response modifier, OK-432. Overall survival was not improved by OK-432. However, among the patients with a negative SUPS skin reaction before treatment, those who received OK-432 had a significantly better outcome than those without OK-432. Cox multivariate regression analysis indicated that postoperative therapy with or without OK-432 was a significant prognostic factor for patients receiving chemotherapy and immunochemotherapy who had a positive and negative SU-PS skin reaction, respectively. These results indicate that the pretreatment SUPS skin reaction is a possible predictor of the effectiveness of immunotherapy using OK-432.
The optimum duration of postoperative anticancer therapy remains unclear at present. To evaluate the effectiveness of immunotherapy using protein-bound polysaccharide K (PSK) for esophageal carcinoma, a cooperative randomized study involving 18 institutions in Japan was organized by Dr. H. Satou. Using the data from this prospective study, we retrospectively analyzed the outcome for patients surviving longer than 6 months or longer than 1 year, and found that patients receiving PSK for more than 6 months or more than 1 year had a significantly better survival than those receiving PSK for less these times. These findings suggest that PSK therapy should be continued for at least 6 months to improve the prognosis.
A self-administered, short Japanese version of a quality of life (QOL) questionnaire was devised. This questionnaire measured non-disease-specific QOL. It was devised on the basis of the working hypothesis that "attitude towards disease" (F) affects "state of disease" (D), and items related to both F and D were considered. The items were divided into two questionnaires, each of which included certain common key questions. This artice presents the details of our strategy for developing a short Japanese questionnaire to measure non-disease-specific QOL.