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Cholesterol — lowering therapy
Notes
Aggressiveness cers
of screen-detected
breast
can-
The malignant potentials of 248 breast cancers detected by the screening service in Finland were compared with those of 390 control cancers diagnosed before the screening service was establihed. Biological agressivencss, as assessed by DNA flow cytometry, did not increase during the detectable preclinical phase of breast cancer development. Therefore, earliness of diagnosis and effectiveness of screening can not be assessed by biological aggressiveness but results on DNA flow cytometry can help to overcome length bias and overdiagnosis. Clinical indicators, mainly the size of the cancer, imply early diagnosis. Therefore, they are intermediate end-points, which can be used as early indicators of effect of screening on mortality. M Hakama
(I,
University of Tampere, FIN 33101 Tampere, Finland (I)
Lmcet
1995:345:22
l-4
Cholesterol - lowering therapy It has been shown that cholesterol lowering results in a marked decrease in cardiovascular morbidity and mortality, and more recently in total mortality. Angiographic regression studies have shown that regression is possible and progression can be slowed. but the degree of change in stenosis is very small. Other mechanisms must be at work, to account for the marked improvement in clinical events with cholesterol lowering therapy. Recent advances in vascular biology have broadened our understanding of the importance of the endothelium. Through the release of factors such as nitric oxide, the endothelium maintains vasodilatation. inhibits platelet aggregation and smooth muscle cell proliferation. High levels of cholesterol and particularly the oxidized form of LDL are particularly injurious to the endothelium. Animal studies have shown that endothelial vasodilator function can be reversed with cholesterol lowering. The purpose of the study was to assess the impact of cholesterol lowering therapy or the combination of cholesterol lowering and antioxidant therapy on endothelium-dependent coronary vasomotion in patients with hypercholesterolemia and atheros-
clerosis. Forty-nine patients were studied at baseline and after one year of therapy vvith either diet (control group). lovastatin and cholestyramine (LDL lowering group) or lovastatin and probucol (LDL lowering and antioxidant group). Compared vvith control, patients randomized to the LDL lowering group showed a trend towards improved coronary vasolidator responses to acetylcholine (P = 0.08). Patients randomized to combination therapy showed a marked improvement in dilator function (P = 0.01). Cholesterol lowering and antioxidant therapy results in improved endothelium-dependent vasodilator responses to acetylcholine. This observation may have important clinrcal implications for the activity of myocardial ischemia and the reduction of adverse coronary events that is known to occur with cholesterol lowering therapy. TJ Anderson (2) Foothills Hospital, Calgary, AB T2N 2T9. Canada (2) IV Eql
.I Med
1995:332:388-93
A single course of adjuvant intraportal therapy for colorectal cancer
chemo-
Five hundred and thirty-three patients with operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C and S-Fluorouracil starting immediately after surgery, or no adjuvant treatment. Five hundred and five (94%) were evaluable. At a median follow-up of eight years, adjuvant therapy reduced the risk of recurrence by 21% (HR = 0.79: 95% CI 0.62 - I .OO: P = 0.051) and the risk of death by 26% (HR = 0.74: 95% CI 0.57 - 0.97: P = 0.026). The relative reduction of relapse was observed in all subgroups (ie. nodal status, localization) and was largest in patients with tumor involved lymph nodes (Dukes’ C; HR = 0.67: 95% CI 0.45 - 0.99: P = 0.045) and for those with colon cancer (HR = 0.78: 95% Cl 0.56 - I .09: P = 0. IS I ). Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (ie, local relapses, livaer metastases and/or other distant metastases) in the treated group. rather than to a reduction of liver relapses alone. We conclude that part of the benefit obtained with a single course of adjuvant
Aggressiveness cers
of screen-detected
breast
can-
The malignant potentials of 248 breast cancers detected by the screening service in Finland were compared with those of 390 control cancers diagnosed before the screening service was establihed. Biological agressivencss, as assessed by DNA flow cytometry, did not increase during the detectable preclinical phase of breast cancer development. Therefore, earliness of diagnosis and effectiveness of screening can not be assessed by biological aggressiveness but results on DNA flow cytometry can help to overcome length bias and overdiagnosis. Clinical indicators, mainly the size of the cancer, imply early diagnosis. Therefore, they are intermediate end-points, which can be used as early indicators of effect of screening on mortality. M Hakama
(I,
University of Tampere, FIN 33101 Tampere, Finland (I)
Lmcet
1995:345:22
l-4
Cholesterol - lowering therapy It has been shown that cholesterol lowering results in a marked decrease in cardiovascular morbidity and mortality, and more recently in total mortality. Angiographic regression studies have shown that regression is possible and progression can be slowed. but the degree of change in stenosis is very small. Other mechanisms must be at work, to account for the marked improvement in clinical events with cholesterol lowering therapy. Recent advances in vascular biology have broadened our understanding of the importance of the endothelium. Through the release of factors such as nitric oxide, the endothelium maintains vasodilatation. inhibits platelet aggregation and smooth muscle cell proliferation. High levels of cholesterol and particularly the oxidized form of LDL are particularly injurious to the endothelium. Animal studies have shown that endothelial vasodilator function can be reversed with cholesterol lowering. The purpose of the study was to assess the impact of cholesterol lowering therapy or the combination of cholesterol lowering and antioxidant therapy on endothelium-dependent coronary vasomotion in patients with hypercholesterolemia and atheros-
clerosis. Forty-nine patients were studied at baseline and after one year of therapy vvith either diet (control group). lovastatin and cholestyramine (LDL lowering group) or lovastatin and probucol (LDL lowering and antioxidant group). Compared vvith control, patients randomized to the LDL lowering group showed a trend towards improved coronary vasolidator responses to acetylcholine (P = 0.08). Patients randomized to combination therapy showed a marked improvement in dilator function (P = 0.01). Cholesterol lowering and antioxidant therapy results in improved endothelium-dependent vasodilator responses to acetylcholine. This observation may have important clinrcal implications for the activity of myocardial ischemia and the reduction of adverse coronary events that is known to occur with cholesterol lowering therapy. TJ Anderson (2) Foothills Hospital, Calgary, AB T2N 2T9. Canada (2) IV Eql
.I Med
1995:332:388-93
A single course of adjuvant intraportal therapy for colorectal cancer
chemo-
Five hundred and thirty-three patients with operable colorectal carcinoma were randomized to receive either a single course of portal infusion with Mitomycin-C and S-Fluorouracil starting immediately after surgery, or no adjuvant treatment. Five hundred and five (94%) were evaluable. At a median follow-up of eight years, adjuvant therapy reduced the risk of recurrence by 21% (HR = 0.79: 95% CI 0.62 - I .OO: P = 0.051) and the risk of death by 26% (HR = 0.74: 95% CI 0.57 - 0.97: P = 0.026). The relative reduction of relapse was observed in all subgroups (ie. nodal status, localization) and was largest in patients with tumor involved lymph nodes (Dukes’ C; HR = 0.67: 95% CI 0.45 - 0.99: P = 0.045) and for those with colon cancer (HR = 0.78: 95% Cl 0.56 - I .09: P = 0. IS I ). Analysis of the pattern of relapse showed that most of the difference in overall and disease-free survival is to be attributed to a consistent reduction of all kinds of tumor recurrences (ie, local relapses, livaer metastases and/or other distant metastases) in the treated group. rather than to a reduction of liver relapses alone. We conclude that part of the benefit obtained with a single course of adjuvant