Anthracyclines are used extensively in therapy of several types of human cancer where long-term survival and cure are common, such as haematological malignancies and paediatric cancers. They are now increasingly used also in adjuvant therapy of breast cancer, because the results of some trials suggest that anthracycline-containing combinations are associated with better survival than non-anthracycline-containing regimens (Early Breast Cancer Trialists' Collaborative Group, 1998). These trials have, however, only limited follow-up of a few years. Cardiotoxicity is a wellestablished side-effect of anthracyclines, and subclinical cardiotoxicity of adjuvant and other curative therapies might manifest only several decades after treatment when the myocardial reserves start to decrease in old age. This might counterbalance the shortterm absolute survival benefit associated with anthracyclinecontaining regimens over CMF (cyclophosphamide, 5-fluorouracil and methotrexate), which is only about 3% at 5 years of follow-up according to the meta-analysis (Early Breast Cancer Trialists' Collaborative Group, 1998). Cardiotoxicity of anthracyclines may be reduced by low-peak therapies, such as anthracyclines given as long infusions (Legha et al, 1982). A novel iron-chelating agent, dexrazoxane, has reduced anthracycline-associated cardiotoxity in several randomized trials, and apart from one study, it has not reduced response rates (Green, 1998).High-dose chemotherapy is used increasingly in therapy of breast cancer both in the US and Europe (Antman et al, 1997;Grathwohl et al, 1997). In the USA, breast cancer is the most common indication for high-dose chemotherapy given with the support of either bone marrow or peripheral blood stem cell rescue at present (Antman et al, 1997). It is currently highly controversial whether high-dose chemotherapy is superior to conventional-dose chemotherapy either in the adjuvant or the metastatic setting, but several controlled trials are currently in progress to resolve the issue. Favourable results have been obtained with adjuvant highdose therapy in phase II studies (Peters, 1996), and many breast cancer patients with a high risk of relapse are now given high-dose therapy. However, besides its efficacy, the long-term risks of highdose therapy are unsettled. Little is known about the subclinical cardiac toxicity related to high-dose adjuvant therapy, which might be of great importance for the long-term survivors from cancer.Endomyocardial biopsy is the most reliable method to diagnose anthracycline-induced cardiotoxicity. However, a non-invasive method of indium-111 monoclonal antimyosin antibody scintigraphy has been shown to be highly sensitive for detecting cardiac damage. The method is capable for detecting even small areas of myocardial damage or necrosis in a variety of diseases Verna et al, 1995;Astorri et al, 1996;Ballester et al, 1997aBallester et al, , 1997bBengel et al, 1997; Schutz et al, 1997). Moreover, it may be the only non-invasive method currently available for detection o...
Twelve nephrectomies (NEs) were performed in 12 pigs (11-17 kg). Total NE was performed on the left side and partial NE on the right side (lower third of the kidney), thus two-thirds of the total kidney volume was removed. Renal function was studied with 99mTc-diethylenetriaminepentaacetic acid (DTPA) renography and serum urea and creatinine levels preoperatively, and 1 and 2 weeks postoperatively. The pigs were imaged in each session for 30 min by collecting 10-s frames from a posteroanterior (PA) view of an anaesthesized animal. The injected activity was 37 MBq. Serial blood samples were taken from the subclavian vein at 0, 1, 2, 3, 5, 15, 25, 40, 60 and 120 min (six animals) after 99mTc-DTPA injection. The DTPA disappearance rate (DDR) was determined from these samples and in other cases (six animals) a blood sample at 20 min was used. The DDR was also determined from the dynamic gamma imaging data: Regions of interest (ROI) were upper body, spleen, heart and kidneys. The ROI analysis correlated well with the blood sampling data (r = 0.97, P < 0.0001). The reference values for pig DDRs were 0.99 +/- 0.08%/min. These values were 0.71 +/- 0.08%/min at 1 week postoperatively and 0.63 +/- 0.08%/min at 2 weeks. DTPA clearance rates were preoperatively 0.53 +/- 0.06 ml/s; at 1 week postoperatively 0.41 +/- 0.06 ml/s; and at 2 weeks 0.35 +/- 0.06 ml/s. There were no significant differences pre- and postoperatively in creatinine and urea concentrations. The DTPA clearance (ml/s) and disappearance rates (%/min) when determined per kidney area (cm2) increased significantly (P < 0.001 at both 1 and 2 weeks); in 11 of 12 animals the function of the resected right kidney was higher than the split function of the whole right kidney preoperatively. Unilateral nephrectomy initiates a functional adaptation or a growth response in the contralateral kidney to compensate for the loss of a renal mass. These data also indicate that two-thirds of the kidney volume in young pigs can be removed without danger.
Twelve partial nephrectomies were performed in 12 piglets using either the combination (contact and non-contact) Nd:YAG laser technique or a steel scalpel. Additional haemostasis was attempted with ligatures. The renal artery was not clamped and renal cooling was not attempted. Total nephrectomy was performed on the contralateral side. Serum creatinine and urea levels were measured, and 99mTc-DTPA renography was performed pre-operatively and 1 and 2 weeks post-operatively. One week post-operatively the mean serum creatinine level was 35% higher than the pre-operative level in the laser group and 30% higher in the steel scalpel group. Two weeks post-operatively the respective differences were 34 and 24%. The mean urea level 1 week after operation was 50% higher than the pre-operative level in the laser group and 17% higher in the steel scalpel group. Two weeks post-operatively the respective differences were 38% in the laser group and 20% in the steel scalpel group. The mean DTPA disappearance rate was 34% lower 1 week after operation in the laser group and 23% lower in the steel scalpel group when compared with the preoperative state. Two weeks post-operatively the respective changes were 48 and 25%. These data indicate that there is no significant difference in renal function when the Nd: YAG combination laser technique is used in partial nephrectomy as compared with the steel scapel.
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