Intensive Care Unit Analgosedation After Cardiac Surgery in Children with Williams Syndrome : a Matched Case-Control Study.

OBJECTIVE: Cardiovascular abnormalities are common in patients with Williams syndrome and frequently require surgical intervention necessitating analgesia and sedation in a population with a unique neuropsychiatric profile, potentially increasing the risk of adverse cardiac events during the perioperative period. Despite this risk, the overall postoperative analgosedative requirements in patients with WS in the cardiac intensive care unit have not yet been investigated. Our primary aim was to examine the analgosedative requirement in patients with WS after cardiac surgery compared to a control group. Our secondary aim was to compare the frequency of major ACE and mortality between the two groups. DESIGN: Matched case-control study. SETTING: Pediatric CICU at a Tertiary Children's Hospital. PATIENTS: Patients with WS and age-matched controls who underwent cardiac surgery and were admitted to the CICU after cardiac surgery between July 2014 and January 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative outcomes and total doses of analgosedative medications were collected in the first six days after surgery for the study groups. Median age was 29.8 (12.4-70.8) months for WS and 23.5 (11.2-42.3) months for controls. Across all study intervals (48 h and first 6 postoperative days), there were no differences between groups in total doses of morphine equivalents (5.0 mg/kg vs 5.6 mg/kg, p = 0.7 and 8.2 mg/kg vs 10.0 mg/kg, p = 0.7), midazolam equivalents (1.8 mg/kg vs 1.5 mg/kg, p = 0.4 and 3.4 mg/kg vs 3.8 mg/kg, p = 0.4), or dexmedetomidine (20.5 mcg/kg vs 24.4 mcg/kg, p = 0.5 and 42.3 mcg/kg vs 39.1 mcg/kg, p = 0.3). There was no difference in frequency of major ACE or mortality. CONCLUSIONS: Patients with WS received similar analgosedative medication doses compared with controls. There was no significant difference in the frequency of major ACE (including cardiac arrest, extracorporeal membrane oxygenation, and surgical re-intervention) or mortality between the two groups, though these findings must be interpreted with caution. Further investigation is necessary to elucidate the adequacy of pain/sedation control, factors that might affect analgosedative needs in this unique population, and the impact on clinical outcomes.

Processes occurring in the NaCMC/glauconite suspension under the cold plasma treatment. Influence of plasma on adsorptive and stabilizing properties of the system.

The paper presents the studies on the processes at the interface of the colloidal suspensions composed of clay mineral - glauconite (GT) and polysaccharide - sodium carboxymethyl cellulose (NaCMC) with the cold plasma treatment (CPT). The surface composition and chemical binding in NaCMC and GT changes are determined by means of FTIR and XPS (both methods detected the incorporation of oxygen-related functional groups). Moreover, the additional information about both the textural properties and morphological changes on the surfaces before and after CPT are studied using the BET, CHN, SEM HRTEM and STEM-EDS methods. The elemental mapping and scanning electron microscope imaging confirmed the NaCMC adsorption on GT (carbon mapping) and proved the GT surface lost its "house of card structure" after the CPT. As follows the CPT causes the protonation of NaCMC and the polymer cross-linking whereas the GT sample is more oxidized. Moreover, it was found that a significant improvement in the GT/NaCMC system stability and the NaCMC adsorption on the GT surface were a result of the CPT. The obtained data could be used for the colloidal stability of polymer/solid suspensions, thus providing new opportunities for the chemical industry; particularly for preparation of new functionalized materials.

Ureteral Rupture Caused by Accidental Intubation of the Ureter with a Foley-Catheter during Ureterorenoscopy.

We would like to present the case of a 64-year-old woman who underwent ureterorenoscopy and suffered an iatrogenic ureteral lesion due to an accidental intubation of the left ureter with a Foley-Catheter during the procedure. A Double-J-Stent was implanted into the damaged ureter, and 6 weeks later it fully recovered. To our knowledge there are few similar cases described in the literature with none of those having happened during ureterorenoscopy so far.

Homogenization of tissues via picosecond-infrared laser (PIRL) ablation: Giving a closer view on the in-vivo composition of protein species as compared to mechanical homogenization.

Posttranslational modifications and proteolytic processing regulate almost all physiological processes. Dysregulation can potentially result in pathologic protein species causing diseases. Thus, tissue species proteomes of diseased individuals provide diagnostic information. Since the composition of tissue proteomes can rapidly change during tissue homogenization by the action of enzymes released from their compartments, disease specific protein species patterns can vanish. Recently, we described a novel, ultrafast and soft method for cold vaporization of tissue via desorption by impulsive vibrational excitation (DIVE) using a picosecond-infrared-laser (PIRL). Given that DIVE extraction may provide improved access to the original composition of protein species in tissues, we compared the proteome composition of tissue protein homogenates after DIVE homogenization with conventional homogenizations. A higher number of intact protein species was observed in DIVE homogenates. Due to the ultrafast transfer of proteins from tissues via gas phase into frozen condensates of the aerosols, intact protein species were exposed to a lesser extent to enzymatic degradation reactions compared with conventional protein extraction. In addition, total yield of the number of proteins is higher in DIVE homogenates, because they are very homogenous and contain almost no insoluble particles, allowing direct analysis with subsequent analytical methods without the necessity of centrifugation. BIOLOGICAL SIGNIFICANCE: Enzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.

Cost-effectiveness of prostate cancer screening: a simulation study based on ERSPC data.

BACKGROUND: The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. METHODS: Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. RESULTS: Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. CONCLUSION: Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis.

[PSA screening 2013: background and perspectives]. / PSA-Screening 2013: Hintergründe und Aussichten.

In the healthcare political discussions on treatment measures, the controversy over prostate-specific antigen (PSA) screening has taken a leading role in comparison to, for example the relatively undisputed role of breast and colon screening. This has fortunately led to an in-depth critical analysis of the available data. One advantage is the benefit on survival which increases with longer follow-up observation times. When carrying out studies the quantitative extent of this benefit can become obscured by prescreening, prevalent screening, lack of compliance, contamination and healthy screen bias. Nevertheless, the European randomized screening study of prostate cancer (ERSPC) study, for example, showed sufficient statistical power to confirm a screening benefit after 9 or 11 years (evidence level A). However, even for prostate cancer the internal problems of preventive medicine of overdiagnosis and overtherapy are also partially dependent on the age range of the screening population and the screening frequency (28-52%). Unnecessary deficits in the quality of life reduce the benefit of survival in these patients. By using a PSA fine tuning and risk stratification, approximately one third of diagnoses and therapies can be avoided. Additionally, the active surveillance of tumors unsuitable for treatment together with an improved quality of therapy should become of greater importance.

PSA levels and cancer detection rate by centre in the European Randomized Study of Screening for Prostate Cancer.

BACKGROUND: To describe the variation in PSA level by age group and screening round in the ERSPC centres and the variation in cancer detection rates in relation to the underlying prostate cancer incidence. METHODS: Individual data on men invited for the first and second screening rounds according to protocol (excluding early recalls and interval cancers) were obtained from the central database of the ERSPC (cut-off date 31st December 2006). Data were compared between and within centres for the core age group (55-69 at entry). The cancer detection rate (CDR) was compared with the expected background prostate cancer incidence rate in the absence of screening adjusted for the incidence rate in non-attenders and the control arm (IRS). RESULTS: Mean PSA values in the age groups 55-59 years and 65-69 years showed little variation by centre, except for the Dutch centre, where an increase from 1.6 to 1.8 ng/ml and a decline from 2.9 to 2.5ng/ml was observed, respectively. Most tumours were detected at the PSA range 4.0-9.9 ng/ml, with a shift to more cancer detection at 3.0-3.9 ng/ml in the second screening round. There was high variability in the CDR between the centres in both the first (16-46 per 1000) and the second screening rounds (14-50 per 1000). Although the ratio CDR/IRS was less variable, it is somewhat lower in Italy and Switzerland (12 and 14,respectively) and higher in the Netherlands (28), than in most other centres and in Belgium the ratio increased markedly, from 20 to 44 between the first and second rounds. CONCLUSION: There was no clear evidence of a relationship between the underlying incidence and mean PSA levels at screening or the cancer detection rate.

Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer.

OBJECTIVE: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. METHODS: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N=82,816) and the control arm (N=99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. RESULTS: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). CONCLUSION: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm.

Identification of a calcitonin-like diuretic hormone that functions as an intrinsic modulator of the American lobster, Homarus americanus, cardiac neuromuscular system.

In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.

[Status of care for prostate cancer in 2008]. / Stand der Prostatakarzinomvorsorge im Jahr 2008.

Prostate cancer as the second most frequent cause of death due to malignancy in men increasingly represents a problem for health care policy that is further intensified by demographic developments."Not every prostate carcinoma identified early must be treated, but those that require therapy must be detected early!" is the current key message in individual screening programs. This means that the measures undertaken for early detection have to be discussed with the patients to inform them about their disease risk, the need for timely initiation of curative treatment, and on possible side effects. On the other hand,"overtreatment" should be avoided. Study results on the general screening benefit with level A evidence are first expected around 2010. Interim analyses with metastasis rate as the endpoint show a benefit of screening in comparison to the control group. Results of trials with level B evidence support the benefit of individual screening. The"overdiagnosis" of latent carcinomas (2-20%) as a consequence of prostate cancer screening should be dealt with by increasing the use of more precise models for active surveillance. Studies that militate against screening should be considered inadequate upon closer scrutiny since they were conducted in a patient cohort that was too old, the follow-up period was too short, and inappropriate endpoints were set.

Analysis of elements in wine using near infrared spectroscopy and partial least squares regression.

The use of visible (VIS) and near infrared spectroscopy (NIRS) to measure the concentration of elements in Australian wines was investigated. Both white (n=32) and red (n=94) wine samples representing a wide range of varieties and regions were analysed by inductively coupled plasma mass spectrometry (ICP-MS) for the concentrations of calcium (Ca), potassium (K), magnesium (Mg), phosphorus (P), sodium (Na), sulphur (S), iron (Fe), boron (B) and manganese (Mn). Samples were scanned in transmittance mode (1mm path length) in a monochromator instrument (400-2500nm). The spectra were pre-treated by second derivative and standard normal variate (SNV) prior to developing calibration models using partial least squares (PLS) regression method with cross-validation. The highest coefficients of determination in cross-validation (R(val)(2)) and the lowest errors of cross-validation (SECV) were obtained for Ca (0.90 and 9.80mgL(-1)), Fe (0.86 and 0.65mgL(-1)) and for K (0.89 and 147.6mgL(-1)). Intermediate R(val)(2) (<0.80) and SECV were obtained for the other minerals analysed. The results showed that some macro- and microelements present in wine might be measured by VIS-NIRS spectroscopy.

The fluoride cleavable 2-(cyanoethoxy)methyl (CEM) group as reversible 3'-O-terminator for DNA sequencing-by-synthesis - synthesis, incorporation, and cleavage.

A new and promising sequencing technology called sequencing-by-synthesis (SBS) enables fast determination of DNA sequences. 2'-Deoxynucleotides containing the (2-cyanoethoxy)methyl (CEM) group at the 3'-O-position are potential reversible terminators for the SBS technology. Herein we describe the synthesis, the incorporation by several polymerases, and the cleavage of this 3'-O-blocking group using 3'-O-CEM-thymidinyl-5'-O-triphosphate 7 as an example.

A feasibility study on the use of visible and short wavelengths in the near-infrared region for the non-destructive measurement of wine composition.

The aim of this study was to explore the capability of spectroscopy in the visible (Vis) and short wavelength near-infrared (NIR) regions for the non-destructive measurement of wine composition in intact bottles. In this study we analysed a wide range of commercial wines obtained in Australia in different types of bottles (e.g. colours, diameters and heights), including different wine styles and varieties. Wine bottles were scanned in the Vis-NIR region (600-1,100 nm) in a monochromator instrument in transflectance mode. Principal component analysis (PCA) and partial least-squares (PLS) regression were used to interpret the spectra and develop calibrations for wine composition. Due to the relatively small number of samples available full cross-validation (leave-one-out) was used as validation. The coefficient of correlation in calibration [Formula: see text] and the standard error of cross-validation (SECV) were 0.67 (SECV: 0.48%), 0.83 (SECV: 4.01 mg L-1), 0.70 (SECV: 28.6 mg L-1) and 0.50 (SECV: 0.15) for alcohol content, total SO2, free SO2 and pH, respectively, in the set of wine samples analysed. These preliminary results showed that the assessment of wine composition by Vis and short wavelengths in the NIR is possible for either qualitative analysis (e.g. low-, medium- and high-quality grading), or for screening of composition during bottling and storage. Although low accuracy and precision were obtained for the chemical parameters routinely analysed in wine, calibration models for the chemical parameters were considered acceptable for screening purposes in terms of the standard errors obtained.

Prostate cancer screening: results of a prospective trial in Canton Aargau, Switzerland.

INTRODUCTION: Prostate cancer is the most commonly diagnosed cancer in Swiss men and the second leading cause of cancer related death among them (e.g. CH: 1,267 in year 1998). With the population at risk constantly growing these absolute numbers are expected to further increase. While there is no question that aggressive treatment of localised tumour is required for definitive cure of prostate cancer, the application of screening for early stage disease remains controversial. Since 1998 the Clinic of Urology in Kantonsspital Aarau has participated in the ERSPC (European Randomised Study of Screening for Prostate Cancer) study, which is designed to provide data on prostate cancer screening within a prospective randomised controlled setting. METHODS: Men aged between 55 and 70 years were enrolled in the study. From n = 18,361 men invited by a letter to participate, 7,124 (38.8%) agreed and gave their informed consent to be randomised in either a PSA measurement (n = 3,562, group 1) or a control group (n = 3,562, group 2). Men in group 1 with a PSA level ?3.0 ng/ml, n = 372 (10.5%) then underwent ultrasound guided transrectal sextant biopsy of the prostate. RESULTS: Prostate cancer was detected at presentation in every fourth man biopsied (n = 89). Neither the free-to-total PSA ratio nor the PSA density could significantly spare biopsies while sustaining a high sensitivity level. The overall cancer detection rate amounted to 2.5% in PSA tested men. In 7% (n = 5) distant disease was already present. 93% of men with clinically organ confined disease underwent prostatectomy (n = 59) or radiotherapy (n = 22), whilst only (n = 3) chose to follow a policy of watchful waiting. In 92% the histology of the prostatectomy specimens revealed aggressive cancer characteristics according to the criteria of Epstein et al. CONCLUSIONS: Although the clinically relevant tumour characteristics and the relatively low cancer detection rate of 2.5% (less than the lifetime mortality risk of 3% and the morbidity risk of 8%) seem to justify screening in terms of adequate diagnosis and treatment, follow-up until 2008 is needed to prove the benefit in mortality for the prostate cancer screening group over the control group. Furthermore, information from the ongoing ERSPC study is needed in order to assess uncertainties i.e. the degree of overdiagnosis caused by repeated screening and the quality of life adjusted gain in life years. For daily practice a "PSA grey zone" of 4-10 ng/ml can no longer be postulated as only 70% of men in this range presented with organ confined disease. Once the PSA level exceeds 4.0 ng/ml. prostate biopsy should be performed immediately.

[PSA-screening for prostate cancer--yes or no?]. / PSA-screening für das Prostata-Karzinom-- ja oder nein?

Prostate cancer is a mayor health care problem, especially in the industrialised countries of the Western world. At this time it is the second most common cancer reason for death (CH: 1500 men/year) which will even get more importance in the future by demographic developments. While there is no doubt that in individuals early detection of organ confined disease with localised treatment the prostate cancer can be eradicated and individual men be cured there are uncertainties whether mass screening a population will contribute to reducing prostate cancer related mortality. Its value has not been proved definitively by prospective randomised controlled studies. Most of Medical Societies recommend a "well informed" decision by family physicians, where the men between 50-70 years know about the benefits and harms including: risk of cancer, diagnostic procedures, therapeutic consequences and possible side effects. After agreement of early detection a biopsy has to be done directly above a PSA level of 4.0 ng/ml or a suspicious digital rectal examination. A PSA "grey zone" 4-10 ng/ml can not further be postulated. The ratio of free/total PSA gives no support to prolong biopsy in this moment, because an elevated benign prostate with a higher production of free PSA can mask the tumor in the peripheral zone. Results of the ERSPC and the PLCO trials are expected to give information about the benefits and harms of mass screening in 2006/8.

Features and preliminary results of prostate cancer screening in Canton Aargau, Switzerland.

OBJECTIVE: To report the results from Switzerland's participation in the ERSPC from 1998; importantly, epidemiological data showed that Switzerland has one of the highest rates of morbidity and mortality from prostate cancer in the world. The local study protocol was accepted by the ethical committee and after the successful pilot study phase, the centre joined the ERSPC. SUBJECTS AND METHODS: From September 1998 to June 2003 10 300 men accepted an invitation for the study and were then randomized 1:1 into an active screening arm (assessed by testing prostate-specific antigen, PSA) or a control group (no intervention). The re-screening interval is 4 years and is ongoing (beginning in September 2002). The study protocol includes offering a prostate biopsy when the total PSA is >3.0 ng/mL (the main study protocol in agreement with ERSPC requirements) or when the total PSA is 1-3 ng/mL and the free-to-total PSA ratio <20% (side study protocol). RESULTS: During the first 3 years of screening 3562 men aged 55-70 years were screened; 395 (11.1%) of all participants had a total PSA of >3 ng/mL and 251 (7.4%) were eligible for the side-study. In all, 599 (17.2%) of 3562 accepted a prostate biopsy (93% of 646); 120 cases of prostate cancer were detected (3.4% detection rate). The incidence was 2.5% in main study group (positive predictive value, PPV, 24%) and 0.9% in side study group (PPV 13.6%). In radical prostatectomy specimens the cancers were mostly 'significant' (92% in main study group and 87% in side-study group). CONCLUSIONS: A randomized screening study for prostate cancer is feasible in Switzerland. A longer follow-up is needed to address within the ERSPC the primary hypothesis (that there will be a reduction in mortality in the active screening arm) and to determine the level of over/under-diagnosis and over/undertreatment in the active screening and control arms, respectively.

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience.

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.