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Biomedical subjects

Neil Fleshner

Publications and source records attributed to Neil Fleshner.

At least 19 recordsLinked to original sources
PubMed2007

MYH mutations are rare in prostate cancer.

PURPOSE: Oxidative stress is considered a risk factor for prostate cancer development and is associated with the production of reactive oxygen species (ROS). The base excision repair gene MYH protects against ROS-mediated damage to DNA. Inherited MYH mutations predispose to colorectal adenomas and cancer. A compromised base-excision repair function due to defective MYH may contribute to prostate carcinogenesis. Here, we examine the genetic contribution of MYH to prostate cancer risk. METHODS: Patients diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) alone (n = 45), prostate cancer alone (n = 123) or both (n = 82) were screened for the two most common mutations in the MYH gene using PCR-based RFLP analysis. A single patient with an inherited MYH mutation as well as a subset of 26 patients presenting with a family history of colorectal cancer were screened for additional MYH mutations by direct sequencing of the entire coding region. RESULTS: Biallelic germline mutations in MYH were not detected among prostate cancer patients. Only a single patient was a heterozygous carrier for the Y165C missense mutation. Allelic deletion or somatic mutation of the remaining MYH allele was not identified in this patient's tumor DNA. Two patients harbored V22M polymorphism and three patients were carriers of Q324H polymorphism. CONCLUSIONS: MYH mutations are unlikely to contribute to prostate cancer risk.

Adult↗
PubMed2006

Impact of a multi-disciplinary patient education session on accrual to a difficult clinical trial: the Toronto experience with the surgical prostatectomy versus interstitial radiation intervention trial.

PURPOSE: Random assignment to clinical trials involving different treatment modalities can be difficult. We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT; ACOSOG Z0070 NCIC PR10), a randomized trial for early-stage prostate cancer comparing radical prostatectomy (RP), and brachytherapy (BT). A multidisciplinary educational session was developed to improve patient understanding of treatment options and to facilitate accrual. PATIENTS AND METHODS: Prostate cancer referrals were screened and men who met favorable risk criteria (T1c/T2a, prostate-specific antigen [PSA] < 10 ng/mL, Gleason < or = 6) were invited to a structured education session before a specialty consultation. Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a randomized trial. Then, a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial. RESULTS: In May 2002, SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists. The first 27 eligible patients were approached about SPIRIT, consulted both specialties, and viewed an educational video. No patients consented. The multidisciplinary education session was then introduced. Forty-seven education sessions with 263 patients resulted in 34 consents. Of 203 patients who were suitable for the study but declined random assignment, 62 chose surgery, 94 chose brachytherapy, three patients chose external radiotherapy, and 11 chose no treatment. Consent rates for eligible and suitable patients were one in six. CONCLUSION: Men who understand their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to random assignment.

Aged↗
PubMed2006

Comparison of annexin II, p63 and alpha-methylacyl-CoA racemase immunoreactivity in prostatic tissue: a tissue microarray study.

BACKGROUND: Current ancillary markers for diagnosis in prostate biopsies include p63 and alpha-methylacyl-CoA racemase (AMACR). Annexin II (ANXII), a calcium and phospholipid binding protein, is lost in prostate cancer. AIMS: To investigate ANXII expression in order to assess its utility as a novel diagnostic marker in comparison to p63 and AMACR. METHODS: Using immunohistochemistry on six tissue microarrays, ANXII, p63, and AMACR expression was analysed from 210 radical prostatectomy cases. Staining was evaluated in benign and atrophic glands, high-grade prostatic intraepithelial neoplasia (HGPIN), and prostatic adenocarcinoma. Separate scores were given for ANXII, AMACR and p63 expression. RESULTS: Diffuse cytoplasmic expression of ANXII correlated with p63 reactivity in basal cells. Benign glands were positive for ANXII in 286/292 cores (98%) and negative for AMACR in all 292 cores. HGPIN showed heterogeneous expression of AMACR and ANXII. A significantly larger proportion of HGPIN glands were correctly identified as ANXII negative than as positive for AMACR. ANXII loss in prostate cancer was found in 282/320 cores (88%) and correlated with positive AMACR expression (272/320 cores, 85%), which was not statistically significant. There was no statistically significant correlation between ANXII scores and the clinical parameters examined. CONCLUSIONS: Immunohistochemical staining for ANXII is a consistent and reliable marker of prostatic neoplasia. The findings of this study suggest the potential utility of ANXII as a diagnostic aid in prostate cancer histopathology.

Adenocarcinoma↗
PubMed2006

Should finasteride be used to prevent prostate cancer?

Prostate cancer is an important public health problem. Chemoprevention offers an attractive solution because it may lead to decreased disease-specific mortality. Furthermore, because many men are treated radically for prostate cancers that pose little or no threat to life, chemoprevention may also provide an excellent strategy for diminishing treatment-related costs and adverse effects such as erectile and urinary dysfunction. The Prostate Cancer Prevention Trial was a 7-year randomized study of finasteride versus placebo among men aged older than 55 years. All men were intended to have a prostate biopsy at study conclusion. At trial's end, there was a 25% reduction in period prevalence in all prostate cancers (24.4% for placebo vs 18.4% for finasteride). This represents a 6% absolute risk reduction. A larger number of higher-grade cancers were noted among men randomized to finasteride, which post hoc analyses and studies suggest are almost certainly related to previously unrecognized biases in trial design. There continues to be great debate as to the clinical significance of the cancers prevented. It is our opinion that among men who warrant 5-alpha reductase inhibitors (5ARIs) as part of their benign prostatic hyperplasia regimen, cancer prevention should be recognized as an additional benefit of treatment. Furthermore, men with high risk of clinically significant prostate cancer, such as significant family history, abnormal prostate biopsy histologies, and African descent, should be made aware of these findings. Men with significant anxiety or concern about prostate cancer should also be made aware of the risks and benefits of this therapy. Additional trials of antiestrogens, micronutrients, and other 5ARIs, which will mature over the next 2 to 5 years, will better define the role of 5ARIs in prostate cancer chemoprevention.

Clinical Trials as Topic↗
PubMed2006

Climacturia following radical prostatectomy: prevalence and risk factors.

PURPOSE: Following radical prostatectomy urine leakage during orgasm is a poorly defined entity. We defined the prevalence, quantity, bother and coping mechanisms associated with this complication, called climacturia. MATERIALS AND METHODS: A self-administered questionnaire was given to a cohort of sexually active men after radical prostatectomy. We inquired about the frequency, quantity, bother and coping mechanisms associated with climacturia. We also recorded uroflowmetry and an American Urological Association symptom score (International Prostate Symptom Score) in each patient. RESULTS: Of the 42 patients enrolled with a mean age of 58.9 years and average time since radical prostatectomy of 23.6 months climacturia was reported in 19 (45%). Of the men 68% reported that it happened rarely or only occasionally, while 21% reported that it occurred most of the time or always. In terms of urine quantity 58% of respondents reported only a few drops but 16% reported a loss of more than 1 ounce. Of the patients 52% percent reported no or minimal bother but 48% reported that climacturia caused significant bother. Only 21% of respondents thought that it was of significant bother to their partners. Of the respondents 84% emptied the bladder before intercourse and 11% used condoms. Age, Gleason score and time since surgery were not predictors of climacturia. No association between peak urine flow on uroflowmetry or International Prostate Symptom Score and climacturia was found. CONCLUSIONS: Climacturia is a common clinical entity, occurring in almost half of all patients after radical prostatectomy. It can be a significant problem with respect to urine volume loss, associated bother and condom use. Patients must be informed about this complication before undergoing radical prostatectomy.

Adaptation, Psychological↗
PubMed2006

Rethinking 30-day mortality risk after radical prostatectomy.

OBJECTIVES: Although radical prostatectomy (RP) is associated with greater 30-day mortality in older men, the magnitude of the excess risk in older age groups compared with younger ones has not been well characterized. METHODS: Using data from the Ontario Cancer Registry, we identified 11,010 men who underwent RP from 1990 to 1999 in Ontario, Canada and compared the 30-day mortality risk immediately after RP with the 1-month mortality risk in the same population of men 7 to 12 months after RP and that of an age-matched general population of men. RESULTS: Overall, 53 men (0.48%) died within 30 days of surgery. The absolute excess 30-day mortality risk associated with RP was 0.18%, 0.51%, and 0.59% for men aged 50 to 59, 60 to 69, and 70 to 79 years, respectively, and was similar for men aged 60 to 69 and 70 to 79 years (P >0.05). The relative mortality risk within 30 days of RP was approximately nine times the baseline risk (95% confidence interval 3 to 38) and was similar for men in all three age groups (P >0.05). CONCLUSIONS: The results of our study indicate that men aged 70 to 79 years do not have a greater absolute excess or relative risk of 30-day mortality after RP compared with men aged 60 to 69 years.

Aged↗
PubMed2006

Treatment of the inguinal regions in penile cancer: a review of the literature and treatment proposal.

Penile cancer is a rare malignancy affecting only 1 per 100,000 men in North America and Western Europe. Although the majority of men present with clinically negative inguinal lymph nodes, node positivity is associated with a very poor prognosis. Both the management of positive nodes, and the management of clinically negative nodes in intermediate- and high-risk patients remain controversial. Experience with penile cancer is often limited as even tertiary referral cancer centers may see only one or two such patients per year. The literature, which consists mainly of retrospective studies of patients treated over several decades, is not conclusive. We undertook a literature review to address this issue and to propose.

Humans↗
PubMed2006

Surgical wait times for patients with urological cancers: a survey of Canadian surgeons.

BACKGROUND: The wait times for urological cancer surgeries in Canada has increased over the past 2 decades. This is of concern to patients, physicians and other key stakeholders because there is evidence that delaying surgery beyond a recommended threshold could have a negative impact on clinical outcomes. To address these trends, a Canadian surgical wait times (SWAT) initiative has been undertaken to develop a consensus document and make recommendations on appropriate wait times. As a first step, the SWAT steering committee determined that current wait times estimates were required for the four key disease sites; prostate, bladder, kidney and testes. To obtain such data, a survey of Canadian urological surgeons was undertaken. METHODS: A structured electronic mailing strategy was adopted as recommended by Dillman (1978). Standardized data collection forms were sent to members of the Canadian Urological Association (CUA) and attendees to the 2005 CUA meeting. Survey items consisted of respondent demographic data, information on surgical wait times for the four key disease sites and potential barriers to timely cancer surgery. RESULTS: One hundred and five urological surgeons responded to the survey. There was considerable variation in wait times between and within the four disease sites with bladder and kidney cancer surgeries displaying the widest range. Operating room availability and staging tests were identified as the most significant barriers to efficient cancer surgery. CONCLUSIONS: The wide variation in wait times identified in this study suggest that the overall time to treatment from referral is beyond the duration considered by many experts and by the Canadian Society of Surgical Oncology to be acceptable. These issues need to be addressed through a partnership between the key stakeholders in order to reduce the potentially negative impact on clinical outcomes and patient quality of life.

Appointments and Schedules↗
PubMed2006

Does prolonging the time to prostate cancer surgery impact long-term cancer control: a systematic review of the literature.

BACKGROUND: The wait times for prostate cancer surgery in Canada has increased over the past 2 decades. Prolonged wait times have a negative impact on patient quality of life but the effect on long-term cancer control is undefined. We conducted a systematic literature review to examine the best available evidence addressing the following key questions: . What is the reported time interval for prostate cancer patients from the decision to operate until the day of cancer surgery? . Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? . Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e. recurrence free survival, overall survival)? METHODS: A structured literature search of Medline, Pubmed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Database of Abstracts of Reviews of Effects, Healthstar and Google Scholar was performed from January 1980 to January 2006 for published epidemiological studies and international guidelines/consensus documents that evaluated surgical wait times for prostate cancer. Data extracted from eligible studies included median time to prostate cancer surgery from the point of patient contact and adjusted hazard ratios (HR) for wait times. All HR from the included studies were examined for the possibility of statistical pooling via meta analytic techniques. RESULTS: Thirteen studies evaluating wait times for prostate cancers were identified, six of which measured the HR for prostate specific antigen (PSA) recurrence in patients with prolonged wait times. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. Median wait times from various points of patient contact ranged from 42 days to 244 days. In the six Canadian studies identified, wait times ranged from 42 days (consultation to operation) to 83 days (consultation to hospital admission). This was in contrast to national and international guidelines, which recommended a maximum wait time for prostatectomy between 2 to 4 weeks. The association between surgical delay and disease recurrence remained controversial where only two of six epidemiological studies reported at least a statistical trend for an increased risk of PSA recurrence free survival in patients with surgical delays of 3 months or more. CONCLUSIONS: Unlike comparable countries, surgical wait times in Canada appear to be increasing and are well beyond the threshold recommended by national and international expert bodies. Even though the association between surgical delay and disease recurrence remains unclear, there is an ongoing concern that the psychological impact of prolonged waiting could negatively impact patient outcomes. To address these important issues, the surgical wait times (SWAT) initiative is mandated to provide the necessary guidance and recommendations to the federal and provincial governments. Through a partnership of the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of prostate cancer patients and their families.

Appointments and Schedules↗
PubMed2006

Does prolonging the time to testicular cancer surgery impact long-term cancer control: a systematic review of the literature.

BACKGROUND: The wait times for urological cancer surgeries in Canada are beyond those recommended by the Canadian Association of Surgical Oncology. Prolonged wait times have a negative impact on patient quality of life but the effect on long-term cancer control is controversial. We conducted a systematic review of the testicular cancer literature to examine the best available evidence addressing the following key questions: What is the reported time interval for testicular cancer patients from the decision to operate until the day of testicular cancer surgery? Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e. recurrence free survival, overall survival)? METHODS: A structured literature search of Medline, Pubmed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Database of Abstracts of Reviews of Effects, Healthstar and Google Scholar from January 1980 to September 2005 was conducted for published epidemiological studies and international guidelines/consensus documents that evaluated surgical wait times for testicular cancer. Data extracted from eligible studies included median time to diagnosis and to testicular cancer surgery. RESULTS: Five studies evaluating different components of wait times (e.g. delay in diagnosis, delay in orchiectomy) in testicular cancer patients were identified, four of which measured the impact of prolonged delays on relapse free and overall survival. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. In one study from the United Kingdom, median wait time was 30 days from general practitioner referral to surgery and 4 days from diagnosis to surgery. No Canadian studies specific to testicular cancer were identified. The association between surgical delay and clinical outcomes remained controversial where only one of five epidemiological studies reported an association between treatment delay and relapse free and overall survival CONCLUSIONS: Even though the association between surgical delay and disease related clinical outcomes remains controversial, there is an ongoing concern that the psychological impact of prolonged waiting for urological cancer surgery could negatively impact patient outcomes. Additional research is needed to identify the current wait times for testicular cancer in Canada and to develop guidelines and recommendations on what appropriate wait times should be. To address these important issues, the surgical wait times (SWAT) initiative is mandated to provide the necessary guidance and recommendations to the federal and provincial governments. Through a partnership between the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of cancer patients.

Appointments and Schedules↗
PubMed2006

Does prolonging the time to bladder cancer surgery affect long-term cancer control: a systematic review of the literature.

BACKGROUND: Prolonged surgical wait times have significant effects on a patient's psychological well-being and a negative impact on quality of life but the effect on long-term cancer control is controversial. We conducted a systematic review of the bladder cancer literature to examine the best available evidence addressing the following key questions: What is the reported time interval for bladder cancer patients from the decision to operate until the day of bladder cancer surgery? Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e., recurrence-free survival, overall survival)? METHODS: A structured literature search PubMed, Embase, the Cochrane Database and Google Scholar from January 1965 to January 2006 was conducted for published studies and international guidelines/consensus documents that evaluated surgical wait times for bladder cancer. Data extracted from eligible studies included median time to bladder cancer surgery from diagnosis and key patient outcomes, such as survival rate or adjusted hazard ratios (HR). RESULTS: Eighteen studies evaluating wait times for bladder cancer surgery were identified, ten of which measured the association between prolonged waiting time and overall survival or tumor grade. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. Median wait times from various points of patient contact ranged from 29 days (urologist consultation to transurethral resection) to 164 days (general practitioner referral to surgery). In the lone Canadian epidemiological study, which focused on all types of urological cancer, median wait time was 64 days from referral to surgery. This was in contrast to national and international guidelines, which recommended a maximum wait time between 2 and 4 weeks for all cancer surgeries. The association between surgical delay and overall survival remained controversial with some studies reporting a reduced overall survival in patients with prolonged delays, while others failed to find such associations. However, the three studies that measured the association between a delay of (3) 3 months and tumor grade reported that patients in the prolonged delay groups had an overall poorer tumor grade. CONCLUSIONS: In Canada, it appears that current wait times for urological surgeries, such as for bladder cancer, are beyond the threshold recommended by national and international expert bodies. Even though the association between surgical delay and overall survival remains inconclusive, there is evidence to suggest that prolonged delays are associated with an overall poorer tumor grade. To provide the necessary guidance and recommendations on these issues to the federal and provincial governments, the surgical wait times (SWAT) initiative was developed. Through a partnership of the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of bladder cancer patients and their families.

Appointments and Schedules↗
PubMed2006

Does prolonging the time to renal cancer surgery affect long-term cancer control: a systematic review of the literature.

BACKGROUND: Prolonged surgical wait times have significant effects on a patient's psychological well being and a negative impact on quality of life but the effect on long-term cancer control is controversial. We conducted a systematic review of the renal cancer literature to examine the best available evidence addressing the following key questions: What is the reported time interval for renal cancer patients from the initial surgical consultation until the day of renal cancer surgery? Are there recommendations/guidelines in the urological cancer literature and, if so, how do the Canadian times compare? Is there a known association between duration of wait time beyond the recommended standard and clinical outcome (i.e., recurrence-free survival, overall survival)? METHODS: A structured literature search PubMed, Embase, the Cochrane Database and Google Scholar from January 1965 to October 2005 was conducted for published studies and international guidelines/consensus documents that evaluated surgical wait times for renal cancer. Data extracted from eligible studies included median or mean time to renal cancer surgery from diagnosis or referral, and key patient outcomes, such as survival rate or adjusted hazard ratios (HR). RESULTS: Only three studies evaluating wait times for renal cancer surgery were identified. Differences in study data availability, method of analysis and wait time definitions precluded statistical pooling of the findings. Wait times from various points of patient contact ranged from a median delay of 26 days (diagnosis to radical surgery, i.e., nephrectomy) to 82 days (general practitioner referral to radical surgery). One study reported a mean of 23.6 days between referral for surgery to hospital admission for nephrectomy. In the Canadian epidemiological study, which focused on all types of urological cancer, median wait time was 64 days from referral to surgery. This was in contrast to national and international guidelines, which recommended a maximum waiting time between 2 and 4 weeks for all cancer surgeries. There were no epidemiological studies evaluating the association between surgical delay and clinical outcomes such as overall survival. CONCLUSIONS: In Canada, it appears that current wait times for urological surgeries, such as for renal cancer, are beyond the threshold recommended by national and international expert bodies. Then again, the association between surgical delay and overall survival appears to be unexplored. Research in this area is urgently needed. Notwithstanding, the surgical wait times (SWAT) initiative was developed to provide the necessary guidance and recommendations on these issues to the federal and provincial governments. Through a partnership of the key stakeholders, it is the vision of SWAT to ultimately improve the care and quality of life of bladder cancer patients and their families.

Adult↗
PubMed2005

30-day mortality and major complications after radical prostatectomy: influence of age and comorbidity.

BACKGROUND: Radical prostatectomy is associated with excellent long-term disease control for localized prostate cancer. Prior studies have suggested an increased risk of short-term complications among older men who underwent radical prostatectomy, but these studies did not adjust for comorbidity. METHODS: We examined mortality and complications occurring within 30 days following radical prostatectomy among all 11,010 men who underwent this surgery in Ontario, Canada, between 1990 and 1999 using multivariable logistic regression modeling. We adjusted for comorbidity using two common comorbidity indices. Statistical tests were two-sided. RESULTS: Overall, 53 men (0.5%) died, and 2195 [corrected] (19.9%[corrected]) had one or more complications within 30 days of radical prostatectomy. In models adjusted for comorbidity and year of surgery, age was associated with an increased risk of 30-day mortality (odds ratio = 2.04 per decade of age, 95% confidence interval [CI] = 1.23 to 3.39). However, the absolute 30-day mortality risk was low, even in older men, at 0.66% (95% CI = 0.2 to 1.1%) for men aged 70-79 years. In adjusted models, age was associated with an increased risk of cardiac (Ptrend < .001), respiratory (Ptrend = .01), and miscellaneous medical (Ptrend = .058) complications. Similarly, increasing comorbidity was associated with a higher risk of all categories of complications. CONCLUSIONS: Increasing comorbidity is a stronger predictor than age of almost all categories of early complications after radical prostatectomy. The risk of postoperative mortality after radical prostatectomy is relatively low for otherwise healthy older men up to age 79.

Age Factors↗
PubMed2005

A reliable coding system to define screening prostate-specific antigen tests was developed in a case-control study.

OBJECTIVE: To establish the reliability of a coding system for screening and diagnostic prostate-specific antigen (PSA) testing from patient charts. STUDY DESIGN AND SETTING: Two investigators reviewed 448 chart abstractions from a population-based case-control study of PSA screening in the Toronto area. The tests evaluated for reliability were transrectal ultrasound (TRUS), digital rectal examination (DRE), and prostate-specific antigen (PSA). RESULTS: DRE results were found in 87%, PSA results in 65%, and TRUS results in 12% of the 749 charts. Interobserver agreement was 94% for DRE texture (kappa =.885), 95% for DRE asymmetry (kappa = .868), 85% for DRE physician interpretation (kappa = .698), 97% for final DRE result (kappa = .856), and 87% for TRUS (kappa = .769). Physician interpretation modified the final result in only 6.2% of DREs. Interobserver agreement for PSA coding was 91% (kappa = .787). Of PSA results, pure PSA screening with no symptoms of obstructive urination was found in 19%, symptomatic PSA screening in 46%, and diagnostic PSA testing in 35%. CONCLUSION: We have developed a practical and reliable coding system for TRUS, DRE, and PSA in the context of a case-control study of PSA screening.

Biomarkers, Tumor↗
PubMed2005

Differences between urologists in United States and Canada in approach to bladder cancer.

OBJECTIVES: To determine the Canada-United States differences with respect to the detection, diagnosis, surveillance, and treatment of bladder cancer. METHODS: A multiple-choice questionnaire was developed and mailed to 760 American and 516 Canadian urologists between November and December 2002. The areas assessed by the questionnaire included demographics, screening, superficial disease and recurrence, surveillance, muscle-invasive disease, advanced disease, and adjuvant systemic chemotherapy. RESULTS: The survey was adequately completed by 32.3% of American urologists and 40.0% of Canadian urologists (overall response rate 36.2%). Canadian urologists tended to be older and had larger practices than U.S. urologists (P <0.05). With respect to bladder cancer detection, U.S. urologists were more likely to use intravenous urography and cystoscopy than were Canadian urologists (P <0.0001). For patients with superficial disease, a significant proportion of urologists in both countries did not routinely use adjuvant chemotherapy. For surveillance, Canadian urologists performed cystoscopy (P <0.0001) and upper tract imaging (P <0.0001) less frequently than U.S. urologists. Striking differences were noted in the approach to Stage T2a disease, with U.S. urologists advocating radical cystectomy more frequently (P <0.0001). With respect to the type of urinary diversion, Canadian urologists tended to favor conduits (P <0.0001, male and P = 0.002, female). Canadian urologists were also less likely to use adjuvant chemotherapy among patients with advanced disease. CONCLUSIONS: The results of our study have shown that the trend of urologists in the United States is toward more aggressive screening, closer surveillance, an earlier trigger for cystectomy, and more common indications for intravenous chemotherapy.

Adult↗
PubMed2005

Screening with prostate specific antigen and metastatic prostate cancer risk: a population based case-control study.

PURPOSE: Screening of asymptomatic men with prostate specific antigen (PSA) remains a controversial issue. There is limited evidence that screening is effective in reducing mortality from prostate cancer. In the current study we determined if screening with PSA reduces the risk of metastatic prostate cancer. MATERIALS AND METHODS: We conducted a population based case-control study among the residents of Metropolitan Toronto and 5 surrounding counties in Ontario, Canada. Data were obtained from 236 cases of metastatic prostate cancer and 462 controls randomly sampled from the source population and frequency matched to cases for age and area of residence. History of PSA testing, digital rectal examination, symptoms and other data were obtained from medical records and a self-administered questionnaire. The association between PSA screening and metastatic prostate cancer was measured by the Mantel-Haenszel odds ratio stratified by exposure observation time and other potential confounding factors. RESULTS: In asymptomatic men, the frequency of PSA screening as determined from medical records was significantly lower among the cases compared with the controls (odds ratio 0.65, 95% confidence interval 0.45 to 0.93). The odds ratio was 0.52 (0.28 to 0.98) in men 45 to 59 years old and 0.67 (0.41 to 1.09) in those 60 to 84 years old. CONCLUSIONS: In this case-control study screening of asymptomatic men with PSA was associated with a significantly reduced risk of metastatic prostate cancer. The results need to be confirmed in randomized controlled trials.

Aged↗
PubMed2005

Evidence for contamination of herbal erectile dysfunction products with phosphodiesterase type 5 inhibitors.

PURPOSE: We determined if pharmacological dosages of phosphodiesterase type 5 inhibitors (PDE5) inhibitors were present within a group of natural products marketed for the treatment of erectile dysfunction. MATERIALS AND METHODS: Seven herbal products marketed for the treatment of erectile dysfunction were purchased via the Internet or at local health food stores. Specimens were batched, relabeled and blindly analyzed for contamination with PDE5 inhibitors. High performance liquid chromatography and mass spectrometry were used to detect evidence of contamination with sildenafil, tadalafil or vardenafil. RESULTS: Of the 7 tested products 2 contained pharmacological dosages of sildenafil and tadalafil. Contamination with vardenafil was not identified. Mean dosages of sildenafil and tadalafil were 30.2 and 19.7 mg, respectively. CONCLUSIONS: A significant proportion of natural products marketed for erectile dysfunction contains PDE5 inhibitors. Although marketed as natural products devoid of adverse effects, these agents are known to have potentially fatal drug interactions with nitrates. Better regulation of the natural health products industry is urged.

3',5'-Cyclic-GMP Phosphodiesterases↗