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Biomedical subjects

John Trachtenberg

Publications and source records attributed to John Trachtenberg.

At least 19 recordsLinked to original sources

Variants of the hK2 protein gene (KLK2) are associated with serum hK2 levels and predict the presence of prostate cancer at biopsy.

PURPOSE: Increased levels of serum human kallikrein-2 (hK2) and an hK2 gene (KLK2) variant are positively associated for prostate cancer, but the relationships between them remain unclear. We examined five variants of the KLK2 gene to further define its relevance to prostate cancer susceptibility and hK2 levels. EXPERIMENTAL DESIGN: We genotyped 645 men with biopsy-proven prostate cancer (cases) and 606 males with biopsies negative for prostate cancer (controls) for five additional single nucleotide polymorphisms (SNP) across the KLK2 gene and also tested for serum hK2 levels. These SNPs were identified from sequencing the KLK2 gene among 20 patients with aggressive prostate cancer. Odds ratios (OR) for prostate cancer detection and haplotype analysis were done. RESULTS: Among the SNPs studied, the A allele of the KLK2-SNP1 (G>A, rs2664155) and the T allele of the KLK2-SNP5 (C>T, rs198977) polymorphisms showed positive associations with prostate cancer, adjusted ORs for KLK2-SNP1 AG and AA genotypes being 1.4 [95% confidence interval (95% CI), 1.2-1.8; P=0.002] and for KLK2-SNP5 TT or CT genotypes being 1.3 (95% CI, 1.1-1.6; P=0.05). Haplotype analyses also revealed a significant association between prostate cancer and the haplotype containing both risk alleles (ACCTT), OR being 5.1 (95% CI, 1.6-6.5; P=0.005). Analysis of serum hK2 revealed hK2 levels to be significantly increased in association with KLK2-SNP1 AA and AG risk genotypes compared with the GG genotype (P=0.001) and also in association with the ACCTT risk haplotype compared with the most common non-risk haplotype (P=0.05). CONCLUSIONS: These findings suggest a role for the KLK2 gene in prostate cancer susceptibility and imply that this role may be realized at least in part by the induction of increases in hK2 production.

Adenocarcinoma↗

Prostate cancers scored as Gleason 6 on prostate biopsy are frequently Gleason 7 tumors at radical prostatectomy: implication on outcome.

PURPOSE: Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. MATERIALS AND METHODS: We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. RESULTS: Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). CONCLUSIONS: Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy.

Biopsy↗

Making sense of prostate specific antigen: improving its predictive value in patients undergoing prostate biopsy.

PURPOSE: The clinical usefulness of PSA for prostate cancer screening is unclear, although the test remains in common use. New methods to interpret PSA are needed. MATERIALS AND METHODS: We examined a cohort of 2,637 men who underwent prostate biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for prostate cancer, including patient age, ethnicity, family history of prostate cancer, previous negative biopsy, voiding symptoms and prostate volume, we developed risk groups for prostate cancer using recursive partitioning modeling independent of PSA or DRE. We then compared prostate cancer probabilities by PSA ranges by risk group. RESULTS: Of the 2,637 men 1,282 (48.6%) had prostate cancer. Age, ethnicity, family history, previous negative biopsy and prostate volume were predictive for cancer. We constructed 6 risk groups by combining these factors and created tables to assign patients to these groups. Independent of PSA and DRE the probability of cancer ranged from 15% in patients in group 1 to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk group prostate cancer probabilities were refined from 0% to 100%. Patients in the higher risk groups also had higher grade cancer (p <0.0001). CONCLUSIONS: We generated 6 risk groups based on simple risk factors for prostate cancer. When used in the right context and patient, PSA is highly accurate for predicting prostate cancer and permitting rational decision making in patients with abnormal PSA.

Adult↗

Evidence for a biopsy derived grade artifact among larger prostate glands.

PURPOSE: The PCPT has demonstrated a higher incidence of high grade (Gleason pattern 4 or greater) prostate cancers among men randomized to finasteride. One plausible explanation for this finding is that tumor grade as assigned by TRUS guided biopsy is artifactually associated with prostate volume. MATERIALS AND METHODS: We evaluated our institutional data set of TRUS guided biopsies in the last 3 years and identified 369 cases of prostate cancer that fit the criteria of PSA less than 10 ng/ml, biopsy at our center and RP at our center. We identified risk factors for Gleason pattern 4 or greater on biopsy and then on RP specimens from the same patients using univariate and multiple logistic regression analyses. Assessed covariates included patient age, PSA and TRUS volume. RESULTS: Risk factors for Gleason pattern 4 or greater in the biopsy specimens included age (p = 0.01), hypoechoic lesions on TRUS (p <0.001) and TRUS volume (p = 0.008). However, among RP specimens TRUS volume (p = 0.60) became nonsignificant of Gleason pattern 4 or greater on multivariable analysis. Although prostate volume was a predictor for biopsy derived high grade disease it was not predictive of true histological grade. CONCLUSIONS: These data suggest that simply having a larger prostate results in fewer high grade cancers diagnosed at biopsy. Prostatectomy results in the same men suggest sampling artifact, as the distribution of cancer grade is not associated with prostate volume. These findings provide evidence that the increase in higher grade tumors among men in the finasteride arm of PCPT may simply result from prostate volume reduction.

Adult↗

Do the benefits of finasteride outweigh the risks in the prostate cancer prevention trial?

PURPOSE: The Prostate Cancer Prevention Trial demonstrated that finasteride could reduce the incidence of prostate cancer by 25%. However, its use was also associated with an increased risk of high grade cancer resulting in uncertainty surrounding the net benefits of therapy. MATERIALS AND METHODS: We used the Montreal Prostate Cancer Model, a validated Markov model of prostate cancer progression, to compare the forecasted survival in treated and untreated men. The conditions of the model were varied to reflect different assumptions about whether the cancer grade difference observed in the PCPT was real or a treatment associated artifact, and whether cancers detected on end of study biopsies were clinically significant. RESULTS: For a hypothetical cohort of 1,000, 62-year-old men treated with finasteride, an increased survival of 140 life-years (0.14 years per individual) is forecasted if all diagnosed cancers are considered. If tumor grade differences are held to be artifactual, the forecasted benefits increase to 200 life-years. However, if the tumor grade difference is real and only clinically detected cancers are considered, estimated increased survival is only 20 life-years (0.02 years per individual). CONCLUSIONS: The primary prevention of prostate cancer with finasteride looks promising. However, at the present time it should only be considered with caution until we have answered critical questions surrounding the difference in cancer grade observed in the PCPT and the clinical significance of cancers detected on protocol directed end of study biopsies.

Aged↗

A novel serum marker, total prostate secretory protein of 94 amino acids, improves prostate cancer detection and helps identify high grade cancers at diagnosis.

PURPOSE: New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals. MATERIALS AND METHODS: We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer. RESULTS: Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p <0.0001). The adjusted odds ratios for the presence of prostate cancer for patients with the lowest quartile of PSP94, compared to patients in the highest quartile was 2.70 (95% CI 1.8 - 4.0, p <0.0001). Among a subgroup of 649 men in whom PSA had a low predictive value (PSA less than 20 ng/ml, normal DRE and less than 70 years), 260 (40.1%) were found to have cancer. In this subgroup total PSP94 levels helped discriminate between patients with high grade disease (Gleason score 8 or more, median 1.90 ng/ml), moderate grade disease (Gleason score 7, median 2.34 ng/ml) and low grade disease (Gleason score 6 or less, median 2.60 ng/ml, p = 0.007). PSA and the FTPSA were not able to distinguish between patients with different grades in this group. CONCLUSIONS: Patients with low total PSP94 levels had a high probability for having prostate cancer detected at biopsy. The total PSP94 level was able to help identify patients with high grade disease among a subset of patients in whom PSA and FTPSA are least informative.

Adult↗

Photodynamic therapy for urological malignancies: past to current approaches.

PURPOSE: Modern PDT for urological tumors is a potentially selective approach in which in situ photosensitization by a nontoxic drug, locally activated by light, generates cytotoxic reactive oxygen species, causing cell death. While urological clinical experience with PDT is largely limited to treatment for superficial bladder cancer, the advent of novel photosensitizers and technologies for treatment planning, light delivery and dosimetry, PDT for prostate and other urological cancers appears increasingly realistic. MATERIALS AND METHODS: We reviewed the current literature on PDT for urological tumors, in addition to recent emerging data from our laboratory and elsewhere. RESULTS: Remarkable progress has been made in the field of photochemistry and photobiology. Together with improved optical delivery and imaging systems PDT holds promise as an alternative, minimally invasive and potentially curative treatment for localized solid tumors as well as for palliative treatment for isolated, clinically problematic metastases. CONCLUSIONS: Current experience with photodynamic therapy using contemporary photosensitizing agents and light sources is mainly restricted to in vivo experimental models and early phase clinical trails. However, ongoing preclinical work and clinical trials indicate that safer and effective PDT treatments in uro-oncology are imminent.

Genital Neoplasms, Male↗

Population based survival data on urachal tumors.

PURPOSE: Urachal carcinoma accounts for less than 1% of all bladder cancers. Limited data exist on disease related outcomes originating from case reports and select referral centers. We describe a population based outcomes analysis with long-term followup in patients in the province of Ontario. MATERIALS AND METHODS: We reviewed the data source of the Ontario Cancer Registry for patients diagnosed with urachal cancer during 1976 to 2001. A cohort of 40 patients with urachal adenocarcinoma was found. Primary outcome measures were overall and disease specific survival. The effect of patient age, sex, grade, stage and university vs nonacademic treating hospital as predictors of outcome was determined. RESULTS: Median patient age was 52 years. Median followup was 72.7 months. Mean overall survival +/- SD was 121.6 +/- 21 months. Mean disease specific survival in patients treated operatively was 165 +/- 27 months with 5 and 10-year disease specific survival of 61.3% and 49.2%, respectively. Disease specific mortality was not evident after 7 years from diagnosis. Well differentiated tumors in a third of the patients were associated with a 90% cure rate when treated operatively. Well differentiated tumors, and noninvolvement of adjacent organs and the peritoneum correlated with better prognosis (p = 0.004, p = 0.03 and 0.045, respectively). CONCLUSIONS: Urachal adenocarcinoma occurs in all age groups. Long-term disease specific survival can be achieved with partial cystectomy. Covariates associated with better disease specific survival are well differentiated tumor grade and the absence of adjacent organ or peritoneal involvement. No relapses were observed after 7 years.

Adenocarcinoma↗

Nomogram prediction for prostate cancer and aggressive prostate cancer at time of biopsy: utilizing all risk factors and tumor markers for prostate cancer.

BACKGROUND: There is a large amount of confusion in interpreting prostate specific antigen (PSA) values for prostate cancer. More precise risk assessments for prostate cancer detection are needed for men faced with an abnormal PSA. METHODS: We studied a sample of 2,637 men who underwent a prostate biopsy for an abnormal digital rectal exam (DRE) or PSA. Using factors including age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA, we constructed nomograms to predict the probability of prostate cancer at biopsy. RESULTS: Of the 2,637 men, 1,282 men (48.6%) had prostate cancer detected. Age, ethnicity, family history of prostate cancer, a previous negative biopsy, prostate volume, DRE and PSA were all significant predictors of prostate cancer. Nomograms were constructed based on these factors to predict the risk of prostate cancer and of aggressive prostate cancer (defined as a Gleason Score 7 or more). The positive predictive value varied from 5% to 95% based on the nomograms. The nomograms were validated using bootstrapping methods and the expected and observed proportions were found to be highly concordant. CONCLUSIONS: For men with an abnormal PSA or DRE, the risk for prostate cancer can be accurately estimated using a nomogram based on age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA. This tool will aid physicians and patients in determining the need for prostate biopsy.

Adult↗

The use of genetic markers to determine risk for prostate cancer at prostate biopsy.

PURPOSE: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam. EXPERIMENTAL DESIGN: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostate-specific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms. RESULTS: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with the TT genotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1 gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer. CONCLUSIONS: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.

Adenocarcinoma↗

Male BRCA1 and BRCA2 mutation carriers: a pilot study investigating medical characteristics of patients participating in a prostate cancer prevention clinic.

BACKGROUND: Male BRCA1 and BRCA2 mutation carriers are at an increased risk to develop prostate cancer and are subject to screening protocols for high-risk men. The utility of targeted screening, and the clinical and pathological features associated with prostate cancer, have received little attention in this population. METHODS: We report on the clinical screening and pathological characteristics of a group of 19 men with BRCA1 or BRCA2 mutation, as compared to an age-matched group of men with a family history of prostate cancer. RESULTS: Mutation carriers were significantly more likely to have an elevated PSA at first visit (P = 0.03). Prostate cancer was twice as likely to be diagnosed in mutation carriers although this difference was not statistically significant (P = 0.55). CONCLUSIONS: Prostate cancer surveillance of BRCA1 and BRCA2 mutation carriers is warranted. Further research on larger cohorts is needed to evaluate whether unique pathological prostate cancer characteristics exist in these men.

Adult↗

Techniques for delivery and monitoring of TOOKAD (WST09)-mediated photodynamic therapy of the prostate: clinical experience and practicalities.

Photodynamic therapy of solid organs requires sufficient PDT dose throughout the target tissue while minimizing the dose to proximal normal structures. This requires treatment planning for position and power of the multiple delivery channels, complemented by on-line monitoring during treatment of light delivery, drug concentration and oxygen levels. We describe our experience in implementing this approach in Phase I/II clinical trials of the Pd-bacteriophephorbide photosensitizer TOOKAD (WST09)-mediated PDT of recurrent prostate cancer following radiation failure. We present several techniques for delivery and monitoring of photodynamic therapy, including beam splitters for light delivery to multiple delivery fibers, multi-channel light dosimetry devices for monitoring the fluence rate in the prostate and surrounding organs, methods of measuring the tissue optical properties in situ, and optical spectroscopy for monitoring drug pharmacokinetics of TOOKAD in whole blood samples and in situ in the prostate. Since TOOKAD is a vascular-targeted agent, the design and implementation of the techniques are different than for cellular-targeted agents. Further development of these delivery and monitoring techniques will permit full on-line monitoring of the treatment that will enable real-time, patient-specific and optimized delivery of PDT.

Bacteriochlorophylls↗

Reliability and validity of the PORPUS, a combined psychometric and utility-based quality-of-life instrument for prostate cancer.

BACKGROUND: Although utility-based quality-of-life instruments are often used in economic evaluations and psychometric instruments in treatment evaluations, these are complementary approaches to assessing outcomes. In this study we developed and tested these two forms of quality-of-life instruments, both based on a single, validated, health classification system. OBJECTIVES: To assess the measurement properties (reliability and validity) of two newly developed psychometric and utility-based instruments for assessing outcomes associated with prostate cancer. METHODS: 141 men with cancer of the prostate (CaP), treated with radical prostatectomy, radiation therapy, hormonal therapy, and/or chemotherapy were assessed with both instruments and other standard psychometric and utility-based instruments. RESULTS: Analyses indicate the test instruments are reliable and valid. Full-scale correlations between the instruments and standard instruments indicate validity, as do correlations of key subscales, and an evaluation of linear associations with the UCLA-Prostate Cancer Symptom Scales. CONCLUSION: Evidence from this study supports the reliability and construct validity of the tested instruments. Prostate cancer outcomes can now be assessed by a combination of psychometric and utility-based methods, allowing a ready comparison of derived outcomes.

Aged↗

Sexual dysfunction after radical prostatectomy: prevalence, treatments, restricted use of treatments and distress.

PURPOSE: Cancer of the prostate (CAP) is one of the most common malignancies affecting North American men with about 215,000 new cases and 35,800 CAP related deaths annually. The most prevalent intervention for localized CAP is radical prostatectomy (RP) with 10-year survival rates approaching 90%. Studies of men in post-RP recovery indicate that 44% to 75% experience sexual dysfunction and more than 60% experience distress in reaction to sexual dysfunction problems. These findings are increasingly significant as prostate specific antigen testing continues to increase CAP detection rates, resulting in more and younger post-RP patients confronting sexual dysfunction. MATERIALS AND METHODS: A MEDLINE database search was performed for articles published from 1966 to September 2004. RESULTS: Despite effectiveness 30% to 50% of patients who turn to sexually assistive aids after RP discontinue use within a year. This suggests that the achievement of physical responsiveness to an aid is necessary but it is not a sufficient factor in long-term sexual adaptation. Current research exploring this gap between effectiveness and ongoing use supports a broader perspective of sexual dysfunction emphasizing several factors, including perceptions of inadequacy, anxieties in regard to performance and depression in each member of the couple, overly enthusiastic expectations, partner physical/emotional readiness to resume active sex, the meaning to the couple of using a sexual aid and the quality of the nonsexual relationship of the couple. CONCLUSIONS: Our findings reveal the need to explore broader strategies for improving patient coping ability and adaptation. They also point to the need to explore the role of resumed satisfying sexuality in overall quality of life following treatment.

Adaptation, Psychological↗

Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in relation to the patient's risk profile for progression.

Lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) is a slowly progressing disease, with some patients progressing more rapidly than others. In 80% of patients who progress this is caused by the worsening of symptoms. The physician can predict the risk of progression from the patient's clinical profile; increased symptom severity, a poor maximum urinary flow rate (Qmax), and a high postvoid residual urine volume (PVR), are major risk factors for overall clinical progression of LUTS/BPH. A large baseline prostate volume and a high serum prostate-specific antigen (PSA) level are the predominant risk factors for developing acute urinary retention. After predicting risk, the most appropriate treatment should be established by balancing the benefits of treatment against the possible risks and bother resulting from adverse events. From the Medical Therapy Of Prostatic Symptoms study it can be concluded that monotherapy with an alpha1-adrenoceptor (AR) antagonist is an appropriate treatment for many patients with LUTS/BPH. However, for those at high risk of progression (those with a large prostate volume and high PSA level), it appears more appropriate to add a 5alpha-reductase inhibitor to the alpha1-AR antagonist to obtain maximum relief of symptoms, and ideally to halt the progression of the disease. This was confirmed by the RAND Appropriateness Method study, in which 12 urologists determined the most appropriate treatment for patients with LUTS/BPH based on their clinical profile, combination of clinical variables and/or risk factors. This study also indicates that patients at very high risk of progression, with severe obstruction (poor Qmax and high PVR), are potential candidates for immediate surgery.

5-alpha Reductase Inhibitors↗

Serum insulin-like growth factor-I levels and prostatic intraepithelial neoplasia: a clue to the relationship between IGF-I physiology and prostate cancer risk.

Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) among patients who presented for prostate biopsy because of an abnormal serum prostate-specific antigen level or digital rectal exam. We measured serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) prior to prostate biopsy and compared them between 103 men with HGPIN (cases) and 205 men with normal prostate histology (controls). The mean IGF-I level in patients with HGPIN (130.2 ng/mL) was significantly higher compared with controls (118.8 ng/mL, P = 0.01). The mean IGFBP-3 level in patients with HGPIN (2,393.9 ng/mL) was also higher compared with controls (2,276.0 ng/mL, P = 0.06). After adjusting for age, prostate-specific antigen, digital rectal examination, and ethnic background, the odds ratio for a HGPIN diagnosis among men in the highest relative to the lowest quartile of serum IGF-I level was 1.94 (95% confidence interval, 1.0-3.7; P = 0.04). The potential association between a high serum IGF-I level and the presence of HGPIN may represent an important clue to understanding the basis for the relationship between IGF-I physiology and prostate cancer risk. Larger studies will be required to confirm this relationship.

Aged↗

Canadian guidelines for the management of benign prostatic hyperplasia.

OBJECTIVE: To develop the first Canadian guidelines for the management of lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH). METHODS: These guidelines, developed under a mandate provided by the Canadian Urological Association (CUA), were a collaborative effort between the CUA guidelines committee and the Canadian Prostate Health Council. BPH guidelines developed by the American Urological Association, the European Association of Urology, the World Health Organization International Consultation on BPH, and similar committees from Germany, Sweden and Australia were reviewed. The committee further reviewed a systematic literature search, updated to May 2004, and systematically derived Canadian urological opinion data. RESULTS: The subsequent Canadian BPH guidelines were developed as an evidence based consensus among the committee members. Mandatory evaluation includes history, physical examination and urinalysis, while a symptom inventory and PSA in selected patients are recommended. Serum creatinine, uroflow, voiding diary, post void residual and sexual function questionnaire are optional. Unless there is an indication, other related tests are not recommended. Treatment choices should be governed by the severity of the symptoms, bother and patient preference. Guidelines for medical, surgical and minimally invasive treatment as well as special considerations are described in terms of guideline, option and recommendation. CONCLUSIONS: Diagnostic and treatment guidelines for BPH reflect the Canadian social priorities, economics, socialized medical practice, manpower issues, and medicolegal considerations.

Canada↗