Dieter Schönitzer

Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the federal state of tyrol, Austria

Objectives. To monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not introduced. Methods. In 1993, PSA testing was made freely available to men aged 45 to 75 years in the Federal State of Tyrol, Austria. At least two thirds of all men in this age range have been tested at least once during the first 5 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. The IMX assay was used. Digital rectal examination was not part of the screening examination. Results. Significant migration to lower stages has been observed since the introduction of this screening program. A reduction in mortality rates in the rest of Austria from 1993 onward has occurred, with the reduction in Tyrol much greater; the mortality remained fairly constant between 1993 and 1995 and subsequently fell. The trends in prostate cancer mortality rates since 1993 differ significantly between Tyrol (P = 0.006) and the rest of Austria. On the basis of the age-specific death rates averaged from 1986 to 1990, the difference between the number of expected and observed deaths from prostate cancer in Tyrol was 22 in the group aged 40 to 79 years in 1998 and 18 the following year. Conclusions. These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely to be due to aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will only become apparent in the years to come.

Properties of low density lipoproteins relevant to oxidative modifications change paradoxically during aging

Atherosclerosis is a common problem among the elderly. Because lipid peroxidation is considered a contributor to the development of atherosclerosis, we compared oxidative properties of lipoproteins in an otherwise healthy (SENIEUR-classified) aged population (65-74 years) with young controls (18-30 years). Relative amounts of oxidatively altered low density lipoprotein (LDL), estimated by means of an antibody against LDL modified by 4-hydroxynonenal, a product of lipid peroxidation, were increased marginally in serum from the elderly (9.8 vs. 7.4%, P = 0.07). In contrast, isolated LDL from the elderly revealed a decreased susceptibility to in vitro oxidation: the lag time was increased (2.34 vs. 2.10 h, P < 0.01), and the maximal rate of LDL oxidation decreased (0.88 vs. 1.01 O.D./h, P = 0.001). However, there were no age-related changes in lipid composition of native LDL and consumption of fatty acids during in vitro oxidation. The serum concentrations of ascorbic acid and most lipophilic anti-oxidants (the latter expressed per g serum lipids) were significantly decreased in the elderly except tocopherols which tended to be higher. In conclusion, our data reveal paradox age-related alterations of LDL as to its behaviour in oxidation in vivo vs. in vitro.

PSA-based screening for prostate cancer in asymptomatic younger males: pilot study in blood donors.

The efficacy and success of a screening program for prostate cancer in young and healthy asymptomatic volunteers are described.

Screening for prostate cancer: updated experience from the Tyrol study.

The aim of the Tyrol study was to monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not strictly organized and not free of charge. In 1993, PSA testing was made freely available to men between the ages of 45 and 75 years in the Federal State of Tyrol, Austria. At least 70% of all of the men in this age range have been tested at least once during the first 10 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. Since 2001, complexed PSA also has been measured. Digital rectal examination was not part of the screening examination. Significant migration to lower clinical and pathological stages has been observed since the introduction of this screening program. These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely a result of aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will become apparent in the years to come.

Estimation of reference intervals from a senieur protocol compatible aged population for immunogerontological studies

Because many laboratory values change with age, the study of healthy aging as well as diagnosis of disease in geriatric patients requires specific age-corrected reference intervals. We have established such reference intervals for a healthy population aged 65-74 years by selection of a sample group applying the clinical criteria of the SENIEUR protocol and we have compared them with those of a young control group (20-33 years) fulfilling the same criteria. Significant or minor elevations were seen, e.g. for plasma concentrations of fasting glucose, urea, total and LDL-cholesterol, triglycerides, gamma-glutamyl-transferase, alkaline phosphatase, erythrocyte sedimentation rate and serum neopterin levels. These reference intervals can be used for selecting a SENIEUR compatible population aged between 65 and 74 years. Additionally, plasma lipid parameters (cholesterol, triglycerides) are proposed to be included in the SENIEUR protocol.

Session 8 S26. Prostate cancer mortality after introduction of prostate-specific antigen mass screening in the Federal State of Tyrol, Austria

OBJECTIVES To monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not introduced. METHODS In 1993, PSA testing was made freely available to men aged 45 to 75 years in the Federal State of Tyrol, Austria. At least two thirds of all men in this age range have been tested at least once during the first 5 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. The IMX assay was used. Digital rectal examination was not part of the screening examination. RESULTS Significant migration to lower stages has been observed since the introduction of this screening program. A reduction in mortality rates in the rest of Austria from 1993 onward has occurred, with the reduction in Tyrol much greater; the mortality remained fairly constant between 1993 and 1995 and subsequently fell. The trends in prostate cancer mortality rates since 1993 differ significantly between Tyrol (P = 0.006) and the rest of Austria. On the basis of the age-specific death rates averaged from 1986 to 1990, the difference between the number of expected and observed deaths from prostate cancer in Tyrol was 22 in the group aged 40 to 79 years in 1998 and 18 the following year. CONCLUSIONS These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely to be due to aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will only become apparent in the years to come.

Use of Donor-Specific T-Cell Lines for Monitoring of Human Allograft Recipients

Donor-specific and highly cytotoxic T-cell lines (TCL) as well as lectin-induced TCL were established from pretransplant lymphocytes of 6 cadaveric renal allograft recipients. These TCL were used in the 125I-staphylococcus protein A assay to detect IgG antibodies in pre- and posttransplant sera of these patients preferentially binding to autologous donor-specific TCL. Such antibodies were detected in pretransplant sera from 4 of these 6 allograft recipients. Antibody levels in these 4 patients and in 1 additional case who became positive after transplantation further increased during acute cellular rejection episodes. They disappeared after successful treatment but remained elevated until transplantectomy for treatment of irreversible rejection in 1 case. IgG antibodies binding to autologous lectin-induced TCL were detected in only 1 patient and exhibited a pattern clearly different from those binding to donor-reactive TCL. Although attempts to define the antigenic specificity of the autoantibodies binding to donor-specific TCL by genetical and biochemical means has remained unsuccessful so far, the demonstration of their relationship to in vivo expansion of donor-reactive immune cells deserves further attention.