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PubMed1993

Prevalence of pheochromocytoma and hyperparathyroidism in multiple endocrine neoplasia type 2A: results of long-term follow-up.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant condition in which virtually all affected kindred members have medullary thyroid carcinoma (MTC). However, the penetrance of pheochromocytoma and hyperparathyroidism in affected kindred members is variable, and the true prevalence of these neoplasms is unclear from previous studies. METHODS: Members of MEN 2A kindreds with more than 10 years of follow-up screening for MTC, pheochromocytoma, or hyperparathyroidism were studied. The diagnosis of pheochromocytoma was based on histologic examination and hyperparathyroidism on both parathyroid hyperplasia plus preoperative elevation of serum calcium levels. RESULTS: Eighty-six patients operated on for MTC from 12 different MEN 2A kindreds were studied, with a mean follow-up of 12.9 years of screening for pheochromocytoma (79 patients) and 15.0 years for hyperparathyroidism (78 patients). Pheochromocytomas developed in 42% of patients with MTC, with a range of 6% to 100% in different kindreds. The prevalence of hyperparathyroidism was 35%, ranging from 0% to 53% between kindreds. The average age at diagnosis of MTC, pheochromocytoma, and hyperparathyroidism was 29, 37, and 36 years, respectively. CONCLUSIONS: We conclude that the penetrance of pheochromocytoma and hyperparathyroidism is variable in different kindreds with MEN 2A but that the overall prevalence of pheochromocytoma approximates 40% and that of hyperparathyroidism 35%.

Adolescent↗
PubMedDate not supplied

[A modification of the ortho-toluidine method for determining glucose in the blood].

Modification of the orthotoluidine technique is associated with the necessity to examine blood glucose levels in mice, its dynamics analysis (by 5-6 points), which greatly expands the possibility of an experiment on screening new hypoglycemic agents. Addition of tert-butanol (isobutamol) facilitates the interaction of orthotoluidine with glucose, by enhancing the sensitivity and accuracy of the technique and allowing blood microquantities (10-20 microliters per determination) to be analysed. In terms of its accuracy and reliability, the proposed modification is not virtually inferior to expensive enzymatic techniques. The findings suggest that the modified orthotoluidine technique may be useful in the analysis of glucose levels in dynamics in small laboratory animals.

Animals↗
PubMed1998

Serologic and molecular characterization of an abortigenic strain of equine arteritis virus isolated from infective frozen semen and an aborted equine fetus.

A virus isolated from an aborted equine fetus was determined to be antigenically distinct from several other strains of equine arteritis virus (EAV) by use of a neutralization assay with a large panel of neutralizing monoclonal antibodies. The virus was readily neutralized by polyclonal equine anti-EAV serum. Comparative nucleotide and amino acid sequence analyses indicated that the virus (WA97) isolated from the aborted fetus was virtually identical to a virus (S1971) isolated from imported semen used to inseminate another mare on the farm. Phylogenetic analysis indicated that the WA97/S1971 virus was more related to European than to North American strains of EAV. These sensitive molecular procedures may be useful for epidemiologic investigations of EAV infections. Screening and certification of stallions and frozen equine semen would prevent dissemination of pathogenic strains of EAV.

Abortion, Veterinary↗
PubMed2005

Spinal cord sonography in newborns: anatomy and diseases.

Sonography of the spinal cord is a relatively recent acquisition that makes it possible to evaluate the content of the vertebral canal and study its pathologies. The aim of this study was to verify the reliability of ultrasound images by comparing them with magnetic resonance ones in healthy controls as well as in patients referred to us between 1991 and 2004. In this period, we studied 436 newborns: 88 without any suspicion of disease as normal controls, and 348 with suspected congenital diseases or in order to screen the children of diabetic mothers, a group that has shown an increased incidence of dysraphism. After explaining normal sonograms, we describe the pathological pictures observed in the 12 pathological cases in our series: conus hypomobility in five cases; lack of visualization of the conus medullaris in one case; and an enlarged ependymal canal in six cases. Four cases presented all three pathological conditions, and seven the association of two pathologies. All of these patients also underwent magnetic resonance imaging (MRI), which confirmed the ultrasound findings in four cases: three cases of enlarged ependymal canal and one of tethered cord hypomobility of the roots with an associated lipoma; the MRI findings were normal in the other seven cases. Sonography was highly specific but not very sensitive, because it is partially conditioned by patient collaboration. Nevertheless, subsequent MRI confirmed 37% of the suspected pathological cases. The ultrasound resolution of both normal and pathological spinal cord structures was particularly clear. The images were similar, easily comparable and often identical to the MRI results, although MRI was certainly more sensitive. The advantages of sonography are its non-invasiveness, low cost, the virtually ubiquitous availability of ultrasound equipment, the simplicity and rapidity of the examination, and its specificity. We believe that the indications for its use are lumbo-sacral skin alterations, neurological disorders caused by congenital malformations, traumas due to childbirth or a lumbar puncture, occult dysraphism, all of the compressive spinal cord neo-formations involving nerves, the dura mater and vertebral bone and joint structures, and the screening of the newborns of diabetic mothers.

Case-Control Studies↗
PubMed1996

Fetal fibronectin as a screening test for premature delivery in multiple pregnancies.

OBJECTIVE: To evaluate fetal fibronectin as a screening test for premature delivery in asymptomatic women with multiple pregnancies. METHODS: In the mid-second trimester, the concentrations of fetal fibronectin in the cervical and vaginal secretions of 68 patients with multiple gestations were sampled weekly by monoclonal antibody immunoassay in order to predict preterm labor. RESULTS: The results for the prediction of preterm labor differ according to whether we consider a single positive result (fetal fibronectin > 50 ng/ml) as predictive of preterm labor or whether we only consider at least two consecutive positive results as predictive of perterm labor. The fetal fibronectin test had a sensitivity for preterm birth before 37 weeks of 90.9% and 86.6%, respectively, with a specificity of 68.5% vs. 78.9% and a positive and negative values of 73.1% vs. 76.4% and 88.8% vs. 88.2%, respectively. Similar results were obtained for perterm birth before 34 weeks. CONCLUSIONS: In a condition such as multiple pregnancy which is already at risk for premature delivery the possibility of raising the specificity of the test with virtually no decrease in sensitivity guarantees better recognition of patients likely to develop premature labor. This possibility can be achieved simply by considering two positive consecutive samples as predictive of preterm labor.

Female↗
PubMed1993

Neonatal screening for cystic fibrosis: addition of molecular diagnostics to increase specificity.

Newborn screening for cystic fibrosis (CF) has been carried out on approximately 106,000 neonates in western Pennsylvania since 1987 using the immunoreactive trypsinogen (IRT) assay on dried filter paper blood specimens (DBS). Molecular analysis utilizing a duplicate DBS from the same sample was implemented in November 1989 for newborns having elevated IRT levels. DNA is amplified directly from the DBS and the amplified products are tested for the delta F508 deletion and several common exon 11 mutations. Substituting dUTP for dTTP in the PCR reaction and an initial treatment with uracil N-glycosylase (UNG) virtually eliminates PCR carryover contamination. The number of confirmed cases of CF is 20, giving an estimated incidence of 1:5287 in the western Pennsylvania population. Eight of the CF patients are homozygous and 12 are compound heterozygotes for the delta F508 deletion and a second mutation. Two of the compound heterozygotes carry the G551D mutation and one has the R553X mutation. Twenty-one additional neonates that are heterozygous for the delta F508 mutation are normal carriers for CF. In approximately 55% of the cases, molecular analysis of the CF gene confirmed the diagnosis of CF prior to sweat testing. The incorporation of molecular analysis into our CF screening program increases the specificity of the screening strategy and has the potential to decrease the false positive and sweat test referral rate, reduce parental anxiety, and bring CF infants to the attention of physicians more rapidly.

Cystic Fibrosis↗
PubMed1995

Characterization of mouse CD53: epitope mapping, cellular distribution and induction by T cell receptor engagement during repertoire selection.

The pan-leukocyte antigen CD53 is a member of the poorly understood transmembrane 4 superfamily (TM4SF) of cell membrane glycoproteins. CD53 is proposed to play a role in thymopoiesis, since rat CD53 is expressed on immature CD4-8-thymocytes and the functionally mature single-positive subset, but is largely absent from the intermediate CD4+8+ cells. We have characterized CD53 in the mouse through the production of two new monoclonal antibodies, MRC OX-79 and OX-80, which were raised against the RAW 264 cell line and screened on recombinant CD53 fusion proteins. The epitopes recognized by both antibodies are dependent on disulfide bonding and map to the major extracellular region of CD53, requiring the presence of a single threonine residue at position 154. Mouse CD53 has a molecular mass of 35-45 kDa and is expressed on virtually all peripheral leukocytes, but not on cells outside the lymphoid or myeloid lineages. CD53 expression distinguishes subpopulations of thymocytes in the mouse and resembles the expression pattern of rat CD53. Amongst the immature CD4-8-thymocytes, mouse CD53 is clearly detectable on the earliest CD44high25- subset, but down-regulated on the later CD44high25+, CD44low25+ and CD44low25- stages. Also, the subsequent transient TcR-/low CD4-8+ cells and most CD4+8+ thymocytes express little or no CD53. This is consistent with the idea that cells which are committed to enter the selectable CD4+8+ compartment switch off CD53. The effect of T cell receptor (TcR) engagement on the re-expression of CD53 on CD4+8+ thymocytes was studied both ex vivo and in vitro using F5 mice, transgenic for the H-2b/influenza nucleoprotein-peptide-specific TcR, back-crossed onto an H-2q or H-2b background of RAG-2-deficient mice. CD4+8+ thymocytes from non-selecting H-2q F5 mice are CD53 negative, but in vitro stimulation through the TcR dramatically induces CD53 expression. In contrast, a fraction of CD4+8+ thymocytes from positively selecting H-2b F5 transgenic mice express CD53. Therefore TcR engagement by selecting major histocompatibility complex peptide complexes, or surrogate ligands, induces CD53 expression on otherwise CD53-negative, non-selected CD4+8+ thymocytes. Whether CD53 itself participates as a signaling molecule in further stages of thymic selection is still a matter of speculation.

Amino Acid Sequence↗
PubMed2002

Parathyroid cytology: avoiding diagnostic pitfalls.

BACKGROUND: Interpretation of parathyroid fine-needle aspirates (FNA) remains problematic not only because this type of specimen is rare but also because the pertinent literature is very limited. We systematically reviewed parathyroid FNAs in our files and sought to delineate additional diagnostic criteria. DESIGN: Review of all thyroid and parathyroid aspirates from January 1990 to June 1998 disclosed 12 parathyroid lesions. The final diagnoses included four parathyroid adenomas, one intrathyroidal hyperplastic parathyroid, one intrathyroidal parathyroid adenoma, one atypical parathyroid adenoma (all confirmed by histologic screening or immunocytochemistry), and five parathyroid cysts (all confirmed by immunoassay). Papanicolaou and Diff Quik-stained smears of the parathyroid FNAs were reviewed. The cytologic features were compared and contrasted with those of thyroid FNAs to establish criteria for differential diagnoses. RESULTS: The FNAs of the five parathyroid cysts yielded virtually acellular fluid with a characteristic water-clear appearance and markedly elevated levels of parathyroid hormone. The remaining seven aspirates consisted of moderately cellular smears that showed an admixture of architectural features. Common patterns included cohesive three-dimensional groups, disorganized sheets, papillary fragments, microfollicles, and a single case showing lymphoidlike smears. Although the cells were generally small and round to oval, all cases demonstrated mild to moderate anisokaryosis. The nuclei were hyperchromatic E with coarsely granular chromatin reminiscent of that of small lymphocytes. Occasional nucleoli were noted. Although the cytoplasm was usually pale blue and finely granular with ill-defined borders, two cases showed well-delineated cytoplasmic membranes. Less common findings included cytoplasmic granulation, vacuolization, and rare oxyphilic cells. Naked nuclei were noted in the background of all of the aspirates to varying degrees. Other background findings included the presence of colloidlike material, macrophages, and lymphocytes. One interesting finding that to date has not been reported is the presence of nuclear overlapping (100%) and nuclear molding (71%), which is an uncommon finding in thyroid aspirates. CONCLUSIONS: FNAs of the parathyroid can be easily confused with that of the thyroid, not only because of the clinical similarity between these two types of lesions but also because of the overlap in cytomorphologic features of the aspirated cells. Although no one single cytomorphologic feature is diagnostic, a combination of cytologic parameters noted earlier should raise the possibility of a parathyroid lesion. Aspirates of parathyroid cysts show acellular water-clear fluid with elevated parathyroid hormone measurements.

Adult↗
PubMed1991

Efficiency of locating centres of dot-clusters by human observers.

A spatial interval acuity task was used to determine the efficiency with which observers located the centroids of circular clusters of individually-small elements. A cluster was defined by its radius and by the number of elements within it. The observer's task was to compare the horizontal distance between the centres of two such clusters to a standard distance, and to decide whether it was greater or smaller. The standard distance was made explicit by two markers on the display screen. As expected on statistical grounds, thresholds increased with the radius of the clusters, and decreased as a function of the number of elements. There were considerable individual differences in efficiency between observers, but the best observers achieved efficiencies close to 100% in many of the conditions. One anomalous observer showed virtually no decrease in thresholds as the number of elements increased, and thus her efficiencies declined to as little as 10%. The ability to combine positional information over spatially-separated elements to obtain an estimate of their central tendency appears in general to be high, and may underlie the perceptual biases revealed in certain geometric illusions, such as the Müller-Lyer.

Adolescent↗
PubMed1992

Targeting of "T" lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: role of different lymphocyte subsets.

In an attempt to construct bispecific monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCR alpha/beta+ and CD3+4-8-TCR gamma/delta+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3 + 4 + 8-TCR alpha/beta+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNF-alpha) by all the different subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.

Antibodies, Monoclonal↗
PubMed1994

Incidence of cluster headaches: a population-based study in Olmsted County, Minnesota.

The epidemiology of cluster headache is virtually unknown. Using the unique resources of the Rochester Epidemiology Project for population-based studies, we identified 26 Olmsted County, Minnesota, residents who fulfilled the International Headache Society criteria for newly diagnosed cluster headache between 1979 and 1981. As part of a large study of migraine and cluster headache, we screened more than 6,400 patient records from several diagnostic rubrics to obtain this cohort, accomplished case ascertainment exclusively through medical record review, and assigned diagnoses by the consensus of two neurologists. The age-adjusted incidence was 15.6 per 100,000 person-years (p-y) (95% CI, 8.9 to 22.3) for males and 4.0 per 100,000 p-y for females (95% CI, 0.4 to 7.6). The overall age- and sex-adjusted incidence was 9.8 per 100,000 p-y (95% CI, 6.0 to 13.6) or approximately 1/25 that of migraine. The peak incidence was among men aged 40 to 49 years and women 60 to 69 years. There was a higher than expected prevalence of history of smoking among males with cluster headaches (p < 0.05), supporting the possibility that smoking predisposes to the development of cluster headaches in men.

Adolescent↗
PubMed2006

Exploring strategies for protein trapping in Drosophila.

The use of fluorescent protein tags has had a huge impact on cell biological studies in virtually every experimental system. Incorporation of coding sequence for fluorescent proteins such as green fluorescent protein (GFP) into genes at their endogenous chromosomal position is especially useful for generating GFP-fusion proteins that provide accurate cellular and subcellular expression data. We tested modifications of a transposon-based protein trap screening procedure in Drosophila to optimize the rate of recovering useful protein traps and their analysis. Transposons carrying the GFP-coding sequence flanked by splice acceptor and donor sequences were mobilized, and new insertions that resulted in production of GFP were captured using an automated embryo sorter. Individual stocks were established, GFP expression was analyzed during oogenesis, and insertion sites were determined by sequencing genomic DNA flanking the insertions. The resulting collection includes lines with protein traps in which GFP was spliced into mRNAs and embedded within endogenous proteins or enhancer traps in which GFP expression depended on splicing into transposon-derived RNA. We report a total of 335 genes associated with protein or enhancer traps and a web-accessible database for viewing molecular information and expression data for these genes.

Animals↗
PubMed1998

Surgery for primary hyperparathyroidism 1962-1996: indications and outcomes.

OBJECTIVE: To examine changes over the past three decades in the indications for, and outcomes of, surgery for primary hyperparathyroidism. DESIGN: Survey of a prospective hospital database. SETTING: Royal North Shore Hospital (a tertiary referral and university teaching hospital), Sydney, New South Wales, January 1962 to December 1996. PATIENTS: All 733 patients who underwent neck exploration for primary hyperparathyroidism. RESULTS: The annual number of parathyroidectomies increased virtually exponentially, from a mean of two in 1962-1969 to 73 in 1996. In the 1960s and 1970s, the most common indication for surgery was the presence of renal calculi (58% and 43%, respectively), but in the 1980s there was a marked increase in presentation of asymptomatic disease after biochemical screening (19%). In the 1990s, low bone mineral density detected by osteodensitometry has become the most common indication for surgery (31%). After initial operation, 11 patients (2%) had persistent hypercalcaemia, with five of these cured by reoperation--an overall failure rate of 1%. CONCLUSIONS: Surgery for primary hyperparathyroidism has become increasingly common, with low bone mineral density replacing renal calculi as the most common indication for surgery. Neck exploration in experienced hands results in an overall cure rate of 99%.

Adolescent↗
PubMed2005

Virtual reality colonoscopy simulation: a compulsory practice for the future colonoscopist?

BACKGROUND AND STUDY AIM: As for any manual procedure, the learning curves for medical interventions can have undesirable phases, occurring mostly in the early experience of applying a technique. There have been impressive advances in endoscopic procedures during recent years, and there is an emerging trend that the number of procedures is increasing in parallel with these. In addition, the introduction of screening programs for colorectal cancer will also increase the numbers of procedures needed. Recent developments in medical simulation seem promising with regard to the possibility of "training out" undesirable parts of the learning curve outside the operating room. The aim of this study was to investigate whether the use of the AccuTouch flexible endoscopy simulator improves the early part of the learning curve in colonoscopy training. METHOD: 12 endoscopy trainees, 10 surgeons and two medical gastroenterologists, all with experience in gastroscopy but with no specific colonoscopy experience, were randomly assigned to either simulator training or to a control group. They all received the same theoretical study package and the training group practiced with the AccuTouch colonoscopy simulator until a predefined expert level of performance was reached. All trainees performed their first ten individual colonoscopies described in detail in a separate protocol. RESULTS: Trainees in the simulator-trained group performed significantly better (P=0.0011) and managed to reach the cecum in 52% of their cases (vs. 19% in the control group), and were 4.53 times more likely to succeed compared with the controls. Additionally, there was a significantly shorter procedure time and less patient discomfort in the hands of the simulator-trained group. CONCLUSION: Skills acquired using the AccuTouch simulator transfer well into the clinical colonoscopy environment. The results of this trial clearly support the plan to integrate simulator training into endoscopic education curricula.

Adult↗
PubMed2005

Virtual colonoscopy: issues in implementation.

The following issues and requirements related to the implementation of a CT colonography (CTC) service are important: (i) policies are needed regarding the indications for CTC. Concomitant with this is the need for education of potential referrers and patients. Expectations of the procedure, particularly by general practitioners, may be unrealistic and indications for referral may otherwise be inappropriate. At present there is not general acceptance of CTC for screening asymptomatic persons; (ii) a flexible approach to CT protocols is useful, dependent on the indication for and clinical context of referral, the age and body habitus of the patient; (iii) attention to the issues related to the special skills required by the reporting radiologist. While there is a temptation to regard CTC interpretation as an extension of skills used in interpreting other cross-sectional images, there is a need to realise that there are skills required specific to CTC and there should be adequate provision for training; (iv) matters related to reporting, such as reporting format, and lesions that will be reported/not reported; and (v) informed consent from the patient. Information should be provided with regard to the limitations of CTC, the implications of a positive finding and radiation dosage.

Colonic Diseases↗
PubMed2004

Mining SAGE data allows large-scale, sensitive screening of antisense transcript expression.

As a growing number of complementary transcripts, susceptible to exert various regulatory functions, are being found in eukaryotes, high throughput analytical methods are needed to investigate their expression in multiple biological samples. Serial Analysis of Gene Expression (SAGE), based on the enumeration of directionally reliable short cDNA sequences (tags), is capable of revealing antisense transcripts. We initially detected them by observing tags that mapped on to the reverse complement of known mRNAs. The presence of such tags in individual SAGE libraries suggested that SAGE datasets contain latent information on antisense transcripts. We raised a collection of virtual tags for mining these data. Tag pairs were assembled by searching for complementarities between 24-nt long sequences centered on the potential SAGE-anchoring sites of well-annotated human expressed sequences. An analysis of their presence in a large collection of published SAGE libraries revealed transcripts expressed at high levels from both strands of two adjacent, oppositely oriented, transcription units. In other cases, the respective transcripts of such cis-oriented genes displayed a mutually exclusive expression pattern or were co-expressed in a small number of libraries. Other tag pairs revealed overlapping transcripts of trans-encoded unique genes. Finally, we isolated a group of tags shared by multiple transcripts. Most of them mapped on to retroelements, essentially represented in humans by Alu sequences inserted in opposite orientations in the 3'UTR of otherwise different mRNAs. Registering these tags in separate files makes possible computational searches focused on unique sense-antisense pairs. The method developed in the present work shows that SAGE datasets constitute a major resource of rapidly investigating with high sensitivity the expression of antisense transcripts, so that a single tag may be detected in one library when screening a large number of biological samples.

Computational Biology↗
PubMed1997

Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Nalt Acad Sci US 86:948-952, 1989). Two approaches were taken for new mutation detection; single-strand conformation polymorphism and sequencing to identify micro-mutations in the proximal promoter and exons 1-9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (delta1006-1007), a six nucleotide deletion in exon 8 (delta1441-1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS-B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence.

Adult↗
PubMed2006

Active surveillance versus radical treatment for favorable-risk localized prostate cancer.

Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the pre-screening era. This article summarizes the case for active surveillance for "favorable-risk" prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).

Disease Progression↗