Yoji Iwasaki

Intraoperative radiotherapy for advanced carcinoma of the biliary system

Since November 1973, intraoperative radiotherapy has been performed on five patients with unresectable, advanced carcinoma of the bile duct at the hepatic hilus and six patients with unresectable carcinoma of the gallbladder. A treatment cone with a diameter ranging from 4–10 cm was directly applied at the lesion. A single dose of 2500–3000 rad with 11 to 20 meV electrons was delivered. In all patients, recanalization of the obstructed bile duct was observed by the postoperative cholangiography. The local efficacy was confirmed histopathologically in eight autopsied materials and a specimen resected 105 days after radiotherapy. Mean survival time of patients with unresectable tumors was 10.9 ± 5.6 (SD) months after this radiotherapy. Intraoperative radiotherapy increased the effectiveness and length of palliation for the unresectable lesion.

Intraoperative radiotherapy for advanced carcinoma of the pancreas.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10‐year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P < 0.05); the mean survival time of the IOR group was 4.6 ± 2.6 (SD) and that of the control group 2.5 ± 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Mutagenicity of cyclosporine. Induction of sister chromatid exchange in human cells

To examine whether cyclosporine (CsA) has mutagenic potential against human cells, we analyzed sister chromatid exchange (SCE) induction by CsA using human lymphocytes in vitro. SCE frequencies increased significantly in the lymphocytes treated with 1 microgram/ml and 5 micrograms/ml CsA, though the frequencies seemed to be less than one hundredth of those induced by mitomycin C (MMC). The value of induced SCE depended on CsA concentration. This result indicates that CsA has SCE inducibility. The data also suggest that CsA has a mutagenic effect on human lymphocytes.

Randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma

SummaryWe performed a randomized controlled study of postoperative adjuvant immunochemotherapy with Nocardia rubra cell wall skeleton (N-CWS) and Tegafur for gastric carcinoma between September 1979 and March 1983. A total of 309 patients were entered into this trial. Of the 309 patients, there were 98 evaluable patients in the chemotherapy group and 115 evaluable patients in the immunochemotherapy group. In both groups, Tegafur was given as chemotherapy at a daily dose of 400 to 800 mg, starting at 24–29 days after gastrectomy. In the immunochemotherapy group, 400 μg of N-CWS was injected i. d. within the 2nd postoperative week. It was given weekly during the first month and subsequently monthly for as long as practicable. The patients were surveyed for length of survival in March 1985. The postoperative survival rate was analyzed for all cases, and for patients with various histopathological stages of carcinoma for comparison between the two treatment groups. No statistical difference was detected between the two groups in terms of age, sex, surgical curabilities, or stage of carcinoma. The overall survival rate for all patients was significantly higher in the immunochemotherapy group than in the chemotherapy group (p<0.05). With stage III plus IV disease, 53 patients from the chemotherapy group and 61 patients from the immunochemotherapy group were included for the analysis. As a consequence, a highly significant survival rate was observed in patients with stage III plus IV carcinoma in the immunochemotherapy group (p<0.005) as compared to the chemotherapy group. The overall 5-year (1800 days) survival rate after surgical treatment was 60.2% for the chemotherapy group and 73.2% for the immunochemotherapy group. In patients with stage III plus IV disease, the 5-year survival rates of the two treatment groups were 28.8% and 52.4%, respectively. Accordingly, the 50% survival period of patients with stage III plus IV cancer was 1800 days or more in the immunochemotherapy group, whereas it was only 722 days in the chemotherapy group. These results emphasize the effectiveness of N-CWS as an adjuvant immunotherapeutic agent in postoperative gastric cancer patients.The main side effects of N-CWS were skin lesions in the injected sites and fever, but these were temporary and not serious.

Pathological studies on esophageal varices treated with injection sclerotherapy

Injection sclerotherapy is one of the most effective treatments for esophageal varices. To investigate the fate of esophageal varices embolized with a sclerosant (ethanolamine oleate), we have examined at autopsy the esophageal wall of 14 patients with esophageal varices. When the sclerosant was injected into the varices, at first thrombi formed. After two weeks, granulation tissue appeared and the thrombi were gradually replaced. The granulation tissues were organized slowly after 3 months and in the organized granulation tissue, microscopic recanalization of vessels were seen in 8 out of 9 cases. There was no recurrence of the original varices andde novo varices occurred in one patient. These observations indicate that the varices embolized with ethanolamine oleate become organized in three months after the treatment, and accordingly the esophageal varices are cured. It became also clear that recurrence of the original varices did not occur after the organization.

Rapid estimation of soluble fibrin monomer complexes by high performance liquid chromatography for the purpose of early detection of DIC

Hypercoagulability and DIC are characterized by the presence of SFMC in plasma. We have devised a more rapid method with a quantitative estimation of SFMC by use of HPLC. The normal percentage of SFMC of total fibrinogen content was 2.2 +/- 0.8% in plasma. On the other hand, the amount of SFMC in DIC patients showed a level of 6.8% to 16.7%. The level of SFMC in the third postoperative day after gastrointestinal surgery was between 2.3% and 6.1%. These moderately elevated SFMC levels were suggested to be due to the state of hypercoagulability. Thus, the measurement of SFMC with HPLC is a very useful method to analyze hypercoagulability and DIC.

Trimethadione tolerance test for the quantitative assessment of liver function in rats

The quantitative estimation of the hepatic functional volume in rats was attempted using the serum dimethadione (DMO)/trimethadione (TMO) ratio in a single blood sampling after oral administration of TMO, which we call the TMO tolerance test, in order to develop a means of pre‐operatively assessing hepatic resectability.

Successful treatment of Nocardia asteroides infection with minocycline in kidney transplant patients.

SummaryTwo cases of Noca dia asteroides infection were encountered out of 55 kidney transplant patients at Chiba University Hospital. One patient developed an extrapleural abscess and the other had a pulmonary infiltration with chest wall abscess. The patients were successfully treated by surgical drainage of the chest wall abscesses and by oral administration of minocycline. No adverse effects caused by minocycline were observed during the therapy.From 1900, when the first case of Nocardia infection was reported in Japan, there have been 60 cases reported in Japanese literature through 1973, including those we observed. This is the first report on nocardiosis in kidney transplant patients and on successful treatment of nocardiosis with minocycline in Japan.

Injection Sclerotherapy for Esophageal Varices Associated with Hepatocellular Carcinoma and Liver Cirrhosis

Survival period, causes of death and variceal rebleeding in 20 patients with esophageal varices associated with hepatocellular carcinoma and liver cirrhosis were analyzed to evaluate the effectiveness of injection sclerotherapy. The first injection sclerotherapy successfully stopped active variceal bleeding in all seven emergency cases. These were followed up as elective cases later on. The remaining 13 patients, who had a history of variceal bleeding, were treated as elective cases from the beginning. Endoscopic evaluation of the varices was performed at intervals of six months to one year, after the first sclerotherapy, and recurrence was treated by elective sclerotherapy. 85% of the patients died within one year. Three out of 20 cases were still alive until this study was performed. But, whereas 17 patients died mainly due to hepatic failure and hepatocellular carcinoma, only one patient died due to variceal rebleeding. No deaths were observed to have been directly due to sclerotherapy or its complications. Hence we think that injection sclerotherapy should be considered one of the treatments for esophageal varices in patients with hepatocellular carcinoma and liver cirrhosis.

Fluoresence of metastasized lymph nodes in esophageal cancer following the administration of intravenous eosin yellow using a laser beam

Fifteen patients with esophageal carcinoma received the Photosensitizing dye Eosin Yellow (10 mg/kg) intravenously prior to surgery, and their para-esophageal lymph nodes were then examined for fluorescence using a laser beam at the time of operation. When the time interval between the injection of Eosin Yellow and the operation was 48 hours, 21 out of 22 (95.4 per cent) metastatic lymph nodes exhibited fluorescence and 25 out of 26 (96.2 per cent) non-metastatic lymph nodes did not exhibit fluorescence. This method proved to be invaluable for detecting metastatic lymph nodes macroscopically at the time of surgery for esophageal carcinoma.