Stefan Rydén

Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial.

In a multicenter trial of adjuvant therapy in stage II breast cancer, 719 postmenopausal patients were randomized to one of three treatment regimens: radiotherapy only or in combination with adjuvant tamoxifen for one year, or adjuvant tamoxifen without radiotherapy. At twelve years of follow-up (median 9 years), no statistically significant differences in survival or recurrence-free survival were observed. However, the rate of loco-regional recurrency was lower among patients treated with both radiotherapy and tamoxifen. The rate of bilateral breast cancer was reduced in tamoxifen-treated patients whereas the rate of new primary malignancies other than breast cancer was somewhat higher in tamoxifen-treated patients. Adjuvant therapy in breast cancer may influence not only breast cancer recurrences and mortality but also later disease patterns and cause-specific mortality.

Efficient reduction of loco-regional recurrences but no effect on mortality twenty years after postmastectomy radiation in premenopausal women with stage II breast cancer - A randomized trial from the South Sweden Breast Cancer Group.

PURPOSE To study long term loco-regional and distant recurrence rate and survival after post-mastectomy radiotherapy in combination with oral cyclophosphamide in premenopausal women with stage II breast cancer. STUDY DESIGN A three-armed randomized multicenter phase III trial comparing 1) Radiotherapy (RT) 2) RT+ oral cyclophosphamide for one year (RT+C) and 3) Oral cyclophosphamide only (C). Radiotherapy was administered, in 20 fractions, to 48Gy to the axilla and parasternal lymph nodes, 45Gy to infra- and supraclavicular fossae and 38Gy to the chest wall. Cyclophosphamide was prescribed as 12 courses of 130mg/m(2) od for 14 days every 4 weeks. PATIENTS AND METHODS 367 patients from 15 surgical departments in Southern Sweden, representing 80% of all eligible patients, were included in the trial between 1978-1983. Median age was 47 years, median tumour size was 25mm, and 33% of the patients were lymph node negative. Median follow-up time was 24 years. RESULTS RT reduced the risk at twenty years for loco-regional recurrence in C-treated patients at twenty years with 75% (13.9% vs. 3.5%). The risk reduction was highly significant in both N0 and N+ patients. No reduction in systemic disease or mortality was observed. CONCLUSION Post-mastectomy radiotherapy reduced loco-regional recurrences in this premenopausal population, but no effect was seen on mortality with 20 years follow-up.

A scintillation camera technique for measurements of the reticuloendothelial function - comparison of different methods for measuring RES function.

A highly standardized 99mTc-sulphur colloid was used to evaluate reticuloendothelial system (RES)-function in the normal rat and after RE blockade by gelatin (Haemaccel). Activity distribution in the animals was measured with a scintillation camera technique. Total uptake of activity in the liver was estimated. From the time-activity curves over the liver, the phagocytic index (kphag) was evaluated. Estimation of the uptake rate of the labelled colloid into the liver and into other parts of the RES was also performed using a twocompartment model. Different methods of evaluation of RE function were compared. It was shown that for a proper estimation of the RE function, the whole uptake curve must be considered. Gelatin (Haemaccel) significantly reduced the total colloid uptake by the liver. The colloid uptake rate into the liver was also significantly reduced. Liver specimens after colloid injection were examined by light and electron microscopy showing vacuolation of hepatocytes and sinusoidal cells probably due to pinocytosis. The technique described enables functional studies of the RES. It has the advantage of noninvasive registrations and is based on the same technical facilities as used for routine liver scintigraphy.

Biliary obstruction and susceptibility to biliary sepsis in rats

SummaryThe effect of retrograde intrabiliary (RI) injection ofE. coli was studied in Sprague-Dawley rats with biliary obstruction of different duration (3 days; 2, 4, and 6 weeks). By the injection of 105 colony-forming units (CFU) immediately after occlusion of the common bile duct (CBD), 15 of 18 normal rats survived without clinical signs of infection. In contrast, six of 11 animals in 3-day obstruction (P = 0.04), seven of 12 in 2-week obstruction (P = 0.02), ten of 12 in both 4-week and 6-week obstruction (P = 0.0004) died ofE. coli sepsis after injection of the same amount of bacteria. Animals with longstanding jaundice (4 and 6 weeks) were more susceptible than those with a shorter duration of jaundice (3 days and 2 weeks,P = 0.04). The results warrant the early decompression of the biliary tract in biliary obstruction.

Hepatic reticuloendothelial function in rats with various portasystemic shunts and total liver arterialization

Hepatic reticuloendothelial function was measured in 6 experimental groups of rats with various portasystemic shunts or total liver arterialization by computer calculation of the hepatic uptake rate of intravenously injected 99mTc-sulphur colloid. Marked reduction of the hepatic reticuloendothelial system (RES) function was found both 1 and 3 weeks after the construction of a mesentericocaval or conventional end-to-side portacaval shunt. Hepatic RES function was also lowered both 1 and 3 weeks after a modified portacaval shunt, but the reduction was much less pronounced. Total liver arterialization produced a similar mild reduction of hepatic RES function after 1 week; however, there was no longer any significant reduction after 3 weeks. This study concludes that total liver arterialization ameliorates the negative effect that portasystemic shunting has on hepatic RES function.

Reticuloendothelial function in normal and tumor-bearing rats. Measurements with a scintillation camera technique

The function of the reticuloendothelial system (RES) was evaluated after the inoculation of an experimental tumor in rats. Four groups were studied according to tumor size and site. Reticuloendothelial function was evaluated by measuring the biokinetics of a standardized [99Tcm]-sulfur colloid. Estimation of the uptake rate of the labeled colloid into the liver and other parts of the RES was performed through the use of a two-compartment model. Animals with small liver or subcutaneous tumors showed an increased activity of both the hepatic and the extrahepatic RES. Animals with large retroperitoneal tumors showed a significant decrease in the RE function of the liver. In these animals the function of the extrahepatic RES was not changed compared to controls but was, however, significantly decreased compared to animals with smaller tumors. The findings may reflect a difference in the impact of tumor size on RE function extra- and intrahepatically.

Release of ß-Hexosaminidase after Administration of Different Agents Affecting the Reticuloendothelial System

Plasma levels of a lysosomal enzyme, beta-hexosaminidase (beta-N-acetylglucosaminidase, EC 3.2.1.30) were studied in Wistar rats after administration of 99mTc -sulfur colloid, 198Au colloid, gelatine (Haemaccel), alcohol, methylpalmitate and zymosan. The activity of beta-hexosaminidase was increased 10, 30 and 60 min after the zymosan injection. After 24 and 48 h, enzyme levels had returned to those at outset. The transient release of beta-hexosaminidase probably occurred only during the phagocytosis of zymosan which was evaluated by histological examination of lung, liver and spleen. After the injection of all other agents tested, no significant aberration of beta-hexosaminidase levels was seen. Activity distribution of the radio-labeled colloids revealed differences in organ uptake which were attributed to a difference in colloid particle size. Although the colloids tested have been used extensively for determination of reticuloendothelial function and histological studies suggest phagocytosis of the particles, their administration did not affect plasma beta-hexosaminidase levels. Since lysosomal enzymes are cleared from the blood predominantly by liver macrophages, the primary location of particle phagocytosis may explain the present findings.