The effectiveness of arterial embolization using DSM (Degradable Starch Microspheres, Spherex, Sweden) combined with hyperthermia were investigated in the treatment of VX2 carcinoma in rabbits and also in human hepatic tumors. These microspheres temporarily obstructed the blood flow at the precapillary level. The blood flow in the tumor was inhibited to a greater extent and for a longer period than in normal muscle. The rise in temperature at the tumor site during heating was shown to be significantly higher than in muscle. The pH in the tumor clearly showed a stronger degree of inhibition than that achieved with hyperthermia alone. Histological examination demonstrated no marked damage to the muscle following DSM + hyperthermia. In the patients with hepatic tumor, hyperthermia was performed using an RF Thermotron 8 (8 MHz) externally, followed by injection of 15 ml of DSM combined with anti-cancer drugs via a catheter. The rise of temperature in DSM + chemo-hyperthermia during heating showed a higher value than that with hyperthermia alone and effective cases (PR) totalled 5 from among 8 cases treated. It was concluded that the heating efficiency may be improved by arterial chemo-embolization in the treatment of hepatic tumors.
In non-resectable liver malignancies, concurrent administration of degradable starch microspheres (DSM) and anticancer drugs via hepatic artery has been suggested as a method to increase the concentration of drugs in tumor tissue. DSM also has been known to increase the temperature of tissue when administered at the time of hyperthermia. In the light of these findings we have studied the effect of hepatic arterial infusion of 5-FU and mitomycin C and local hyperthermia in combination with hepatic arterial flow arrest with DSM for the treatment of hepatoma in 11 patients and metastatic liver cancer in 38 patients. Of the 8 patients having hepatoma with increased AFP, all the patients showed a decrease of AFP following the therapy with an average ratio of 65% decrease. Of the 33 patients with hepatic metastasis with increased CEA, 32 patients (96%) showed a decrease of CEA following the therapy (control group with infusion chemotherapy and hyperthermia without DSM: 58%) with an average decrease ratio of 59% (control group: 43%). Of the 26 patients with increased CA 19-9, 22 patients (84%) showed a decrease of CA 19-9 (control group: 75%) with an average decrease ratio of 52% (control group: 29%). This pilot study suggests that the concurrent hepatic arterial infusion of 5-FU, mitomycin C and DSM with local hyperthermia may have the potential to improve selective regional drug effect.
In non-resectable liver malignancies, concurrent administration of degradable starch microspheres (DSM) and anticancer drugs via hepatic artery has been suggested as a method to increase the concentration of drugs in tumor tissue. DSM also has been known to increase the temperature of tissue when administered at the time of hyperthermia. In the light of these findings, we have studied the effect of hepatic arterial infusion of 5-FU and mitomycin C and 2450 MHz microwave local hyperthermia in combination with hepatic arterial flow arrest with DSM for the treatment of hepatoma in 10 patients and metastatic liver cancer in 20 patients. Of the 8 patients with hepatoma with increased AFP, all the patients showed a decrease of AFP following therapy with an average decrease ratio of 64%. Of the 17 patients with hepatic metastasis with increased CEA, 16 patients (94%) showed a decrease of CEA following the therapy (control group with infusion chemotherapy and hyperthermia without DSM: 66%) with average decrease ratio of 50% (control group: 27%). Of the 15 patients with increased CA 19-9, 13 patients (86%) showed a decrease of CA 19-9 (control group: 62%) with an average decrease ratio of 52% (control group: 21%). This pilot study suggests that the concurrent hepatic arterial infusion of 5-FU, mitomycin C and DSM with local hyperthermia may have the potential to improve selective regional drug effect.
Embolizing chemotherapeutic methods are presently used primarily for nonresectable metastatic hepatic carcinoma. Because this kind of carcinoma is generally ischemic, little is expected from embolizing chemotherapeutic methods aimed at tumor necrosis by blood flow obstruction using gelatin sponges. On the other hand, since the arrival rate of Lipiodol is not very good, embolizing chemotherapeutic therapy employing Lipiodol is not expected to be very effective. Consequently, therapies against metastatic hepatic carcinoma have mainly been intraarterial chemotherapies without embolization. Spherex is a transient embolization agent prepared by suspending 60 mg/ml of degradable starch microspheres (hereinafter, DSM) in physiological saline. It was developed by Pharmacia AB, Sweden, as an arterial embolizing agent for embolizing chemotherapy, and it was the first agent approved for use in Japan as an embolization material. DSM is composed of spherical particles approx. 45 microns in diameter prepared by crosslinking partially hydrolyzed potato starch using epichlorohydrin as a crosslinking agent, and it is characterized by gradual decomposition by blood amylase, having a half-life of 20-35 minutes in vitro. Clinically, when Spherex is administered via the arteries, embolization has been found to occur in the arterioles. Furthermore, administration of Spherex via the hepatic artery in combination with an anticancer drug results in the formation of transient reduction of bloodflow, thus making it possible to extend the period of retention of the anticancer drug at a high concentration in the tumorous region. As a result, the local antitumor effect of the anticancer drug may be reinforced, with alleviation of systemic side effects. In clinical tests involving its administration to metastatic hepatic tumors in combination with mitomycin C (hereinafter, MMC), the efficacy is 54.5% with arterial injection therapy with Spherex, which is significantly superior to the 20.0% obtained with arterial injection of MMC alone. Although the rate of side effects exhibited, including pain, digestive symptoms and fever, has been significantly higher in combination with Spherex, myelosuppression indicated by abnormal fluctuations in leukocyte and platelet counts was found to be greater with administration of MMC alone, suggesting its value as an effective future therapy for metastatic hepatic carcinoma. These data indicate that Spherex is not expected to yield an antitumor effect due to long-term blood flow obstruction in the hepatic artery, an effect associated with gelatin sponges heretofore used for embolizing chemotherapy. Instead, it causes a transient occlusion upon one-shot intraarterial injection therapy with MMC, thus extending the retention time of MMC at high concentration in tumorous sections, thereby yielding a high local antitumor effect with MMC.(ABSTRACT TRUNCATED AT 400 WORDS)
Changes in environments and life styles in Japan have caused the recent changes in the time trends of cancer incidence for various sites. Using the data from the Osaka Cancer Registry, time trends during 1966-80 were analysed for cancer incidence of the leading 5 sites: stomach, lung, liver, uterus and breast. Age-adjusted incidence rates of cancers of the stomach (both sexes) and uterus (invasive cancer) decreased to 75% and 64% respectively between the two periods of 1966-68 and 1978-80 while cancers of the lung, liver, and breast reached 163%, 140%, and 143 % during the same period. Decrease of stomach cancer incidence was observed in all age-groups under 79, however, not in the 25-44 age-groups among females. Analyzing the histological data in the registry, it was noticed that estimated incidence of the intestinal type of stomach carcinoma had decreased more rapidly than the diffuse type. In the 30-49 age-groups among females, no decrease was observed of the diffuse type of carcinoma. Concerning lung cancer, a marked increase was observed over 60 years of age. The age-specific incidence curves by birth cohort showed no or very small cohort effects for the population born 1920-29. Among males, percentages of adenocarcinoma and undifferentiated carcinoma have increased and that of epidermoid carcinoma decreased. The change was more marked in the age-groups younger than 59. Liver cancer showed the 3rd highest incidence rate among males and 6th among females. A rising trend in recent years was noticeable over 45 years of age among males. For the invasive uterine carcinoma, the incidence rate has been decreasing in all ages. Comparing these figures with those of whites in Connecticut or of Japanese in Hawaii, the former was higher than the latter and the difference was larger in age-groups over 40. The recent age incidence curve of breast cancer in Osaka came to be close to that in Iceland in 1930-49 when the curve had kept a constant level for age-groups after menopause. Birth cohort effect was observed for in these age classes.