Introduction: Clinical confusion continues to exist regarding the underestimation of cancers amon... more Introduction: Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have previously described our initial experience with magnetic resonance imaging (MRI)-based detection of tumours in the anterior prostate gland. In this report, we update and expand our experience with these tumours in terms of multiparametric-MRI findings, staging, and grading. Furthermore, we report early treatment outcomes with these unique cancers.Methods: We reviewed our prostate MRI dataset of 1117 cases from January 2006 until December 2012 and identified 189 patients who fulfilled criteria for prostate evasive anterior tumors (PEATS). Descriptive analyses were performed on multiple covariates. Kaplan-Meier actuarial technique was used to plot the treatmentrelated outcomes from PEATS tumours.Results: Among the 189 patients who had M...
Canadian Urological Association journal = Journal de l'Association des urologues du Canada
In this paper, we evaluate a sample of urologists' web-sites, based in the United States, usi... more In this paper, we evaluate a sample of urologists' web-sites, based in the United States, using three validated instruments: the Health on the Net Foundation code of conduct (HONcode), DISCERN and LIDA tools. We also discuss how medical websites can be improved. We used the 10 most populous cities in America, identified from the US Census Bureau, and searched using www.google. com to find the first 10 websites using the terms "urologist + city." Each website was scored using the HONcode, DISCERN and LIDA instruments. The median score for each tool was used to dichotomize the cohort and multivariable logistic regression was used to identify independent predictors of higher scores. Of the 100 websites found, 78 were analyzed. There were 18 academic institutions, 43 group and 17 solo practices. A medical website design service had been used by 18 websites. The HONcode badge was seen on 3 websites (4%). Social media was used by 16 websites. Multivariable logistic regressio...
Background Several recent studies have suggested that oestrogen exposure may increase the risk of... more Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed ...
Urologic Oncology: Seminars and Original Investigations, 2014
Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of t... more Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy. We analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival. Of 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39-8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92-6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34-11.45). The main limitations of our study are its retrospective data collection and small absolute number of events. TEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014
Diabetes may be a risk factor for cancer and is associated with worse cancer outcomes. Metformin ... more Diabetes may be a risk factor for cancer and is associated with worse cancer outcomes. Metformin may reduce cancer risk; however, its effect on mortality following cancer remains less clear. EMBASE and Medline were searched through February 10, 2014, for studies reporting an adjusted risk estimate for the effect of metformin therapy on mortality following cancer among diabetic patients. Random-effects models were used to obtain summary HR for the association between metformin and all-cause and cancer-specific mortality. Twenty-one observational studies were meta-analyzed in the primary analysis. Metformin was associated with a reduction in all-cause mortality [HR, 0.73; 95% confidence intervals (CI), 0.64-0.83] and cancer-specific mortality (HR, 0.74; 95% CI, 0.62-0.88). Subgroup analyses by cancer site showed a significant reduction in mortality for colon cancer (four studies, HR, 0.65; 95% CI, 0.56-0.76) but not for breast and prostate cancers. Observational studies indicate that ...
The purpose of this study was to compare the postoperative course of patients with positive stone... more The purpose of this study was to compare the postoperative course of patients with positive stone culture (SC) to patients with sterile SC, and to analyze the predictors for post percutaneous nephrolithotomy (PCNL) sepsis; and to describe the type and resistance patterns of bacteria responsible for post PCNL sepsis. From a cohort of 206 consecutive patients undergoing PCNL, we identified 45 patients with a positive SC (group A) and compared them to patients with a sterile SC (group B). Association between different groups was assessed using Chi square, two-tailed Student's t test and Mann-Whitney U test, as appropriate. Twenty-three patients had postoperative sepsis and regression analysis was performed to identify clinical variables associated with sepsis. Demographics, stone load and hospitalization time were similar in both groups. Postoperative sepsis developed in 31.1 % of patients in group A compared to 5.9 % in group B. In multivariate analysis, only positive SC was an independent risk factor for postoperative sepsis (OR 6.894, 95 % CI 2.31-20.59, P = 0.001). All patients responded well to treatment with no septic complications. Enterococci were the prevalent organism (29.4 %) in patients with a positive SC. Quinolone resistance was high in both gram negative and gram positive bacteria. Patients with an infected stone are at high risk to develop postoperative sepsis despite standard preoperative antibiotic preparation. SC is important to direct further treatment as almost half of patients with positive SC have a discordant or sterile urine culture. Determining the prevalent bacteria and resistance patterns in SC can aid the selection of empiric antibiotic therapy in high-risk patients.
In this study, we estimated the time from first detectable prostate-specific antigen (PSA) follow... more In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.
Urologic Oncology: Seminars and Original Investigations, 2014
To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze i... more To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze its effect on clinical outcome as an indicator of resection quality. The bladder cancer database of a tertiary medical center was queried for patients who underwent complete transurethral resection of bladder tumor (TURBT) between 2008 and 2009. Study end points were absence of detrusor muscle in the surgical specimen and its association with disease recurrence/progression. Detrusor muscle in the surgical specimen was found in 265 of the 332 study patients (79%). The likelihood of finding muscle increased with higher clinical stage (Odds Ratio [OR]-1.8), higher tumor grade (OR-3), larger tumor size (OR-3.2), multifocal disease (OR-1.7), and nonpapillary morphology (OR-2.3). History of bladder cancer, surgeon's experience, and tumor location in the bladder had no effect. In the whole study population, neither tumor recurrence nor disease progression was associated with absence of detrusor muscle. In patients with T1 tumors, absence of detrusor muscle in the specimen was associated with higher early recurrence rate but not worse long-term outcome. Absence of detrusor muscle in TURBT specimens is not determined by the technical difficulty of the procedure or surgical experience. Surgeons are more prone to obtain deep muscle in large, nonpapillary-appearing tumors, likely reflecting efforts to attain accurate staging in these cases. The presence or absence of detrusor muscle may serve as a surrogate of resection quality in patients with T1 tumors, but its general applicability to the overall population of patients undergoing TURBT remains questionable.
Introduction: Clinical confusion continues to exist regarding the underestimation of cancers amon... more Introduction: Clinical confusion continues to exist regarding the underestimation of cancers among patients on active surveillance and among men with repeated negative prostate biopsies despite worrisome prostate-specific antigen (PSA) levels. We have previously described our initial experience with magnetic resonance imaging (MRI)-based detection of tumours in the anterior prostate gland. In this report, we update and expand our experience with these tumours in terms of multiparametric-MRI findings, staging, and grading. Furthermore, we report early treatment outcomes with these unique cancers.Methods: We reviewed our prostate MRI dataset of 1117 cases from January 2006 until December 2012 and identified 189 patients who fulfilled criteria for prostate evasive anterior tumors (PEATS). Descriptive analyses were performed on multiple covariates. Kaplan-Meier actuarial technique was used to plot the treatmentrelated outcomes from PEATS tumours.Results: Among the 189 patients who had M...
Canadian Urological Association journal = Journal de l'Association des urologues du Canada
In this paper, we evaluate a sample of urologists' web-sites, based in the United States, usi... more In this paper, we evaluate a sample of urologists' web-sites, based in the United States, using three validated instruments: the Health on the Net Foundation code of conduct (HONcode), DISCERN and LIDA tools. We also discuss how medical websites can be improved. We used the 10 most populous cities in America, identified from the US Census Bureau, and searched using www.google. com to find the first 10 websites using the terms "urologist + city." Each website was scored using the HONcode, DISCERN and LIDA instruments. The median score for each tool was used to dichotomize the cohort and multivariable logistic regression was used to identify independent predictors of higher scores. Of the 100 websites found, 78 were analyzed. There were 18 academic institutions, 43 group and 17 solo practices. A medical website design service had been used by 18 websites. The HONcode badge was seen on 3 websites (4%). Social media was used by 16 websites. Multivariable logistic regressio...
Background Several recent studies have suggested that oestrogen exposure may increase the risk of... more Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed ...
Urologic Oncology: Seminars and Original Investigations, 2014
Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of t... more Patients receiving cisplatin are at high risk of thromboembolic events (TEEs). The objective of this study was to assess the effect of cisplatin-based neoadjuvant chemotherapy (NCT) on the incidence of perioperative TEEs in patients undergoing radical cystectomy. We analyzed a consecutive sample of 202 patients with urothelial carcinoma treated with radical cystectomy between 2005 and 2013. Data were collected retrospectively by reviewing medical records. Median follow-up was 16.9 months. Events of interest were defined as venous or arterial TEEs occurring from the date of diagnosis to 30 days after surgery. TEE incidence among patients treated with NCT and cystectomy was compared with that among patients treated with cystectomy alone using Fisher exact test and Cox proportional hazards regression. Proportional hazards regression was also used to assess whether TEE is a predictor of cancer progression and survival. Of 202 patients, 17 (8.4%) developed a TEE, including 8 of 42 (19.1%) treated with NCT and cystectomy and 9 of 160 (5.6%) treated with cystectomy alone (risk ratio = 3.39, 95% CI: 1.39-8.24). After adjustment for observation time, there remained an association between treatment with NCT and risk of TEE (hazard ratio = 2.40; 95% CI: 0.92-6.27; P = 0.07). Overall, 7 events occurred before cystectomy and 10 occurred postoperatively. Among patients treated with NCT, 6 of 8 events occurred before cystectomy. Detection of TEE was clinically significant as preoperative TEE was found to be an independent predictor of progression and cancer-specific mortality (adjusted hazard ratio = 3.91, 95% CI: 1.34-11.45). The main limitations of our study are its retrospective data collection and small absolute number of events. TEE occurs commonly in patients with urothelial carcinoma undergoing NCT. Preoperative TEE is an independent predictor of progression and cancer-specific mortality.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014
Diabetes may be a risk factor for cancer and is associated with worse cancer outcomes. Metformin ... more Diabetes may be a risk factor for cancer and is associated with worse cancer outcomes. Metformin may reduce cancer risk; however, its effect on mortality following cancer remains less clear. EMBASE and Medline were searched through February 10, 2014, for studies reporting an adjusted risk estimate for the effect of metformin therapy on mortality following cancer among diabetic patients. Random-effects models were used to obtain summary HR for the association between metformin and all-cause and cancer-specific mortality. Twenty-one observational studies were meta-analyzed in the primary analysis. Metformin was associated with a reduction in all-cause mortality [HR, 0.73; 95% confidence intervals (CI), 0.64-0.83] and cancer-specific mortality (HR, 0.74; 95% CI, 0.62-0.88). Subgroup analyses by cancer site showed a significant reduction in mortality for colon cancer (four studies, HR, 0.65; 95% CI, 0.56-0.76) but not for breast and prostate cancers. Observational studies indicate that ...
The purpose of this study was to compare the postoperative course of patients with positive stone... more The purpose of this study was to compare the postoperative course of patients with positive stone culture (SC) to patients with sterile SC, and to analyze the predictors for post percutaneous nephrolithotomy (PCNL) sepsis; and to describe the type and resistance patterns of bacteria responsible for post PCNL sepsis. From a cohort of 206 consecutive patients undergoing PCNL, we identified 45 patients with a positive SC (group A) and compared them to patients with a sterile SC (group B). Association between different groups was assessed using Chi square, two-tailed Student's t test and Mann-Whitney U test, as appropriate. Twenty-three patients had postoperative sepsis and regression analysis was performed to identify clinical variables associated with sepsis. Demographics, stone load and hospitalization time were similar in both groups. Postoperative sepsis developed in 31.1 % of patients in group A compared to 5.9 % in group B. In multivariate analysis, only positive SC was an independent risk factor for postoperative sepsis (OR 6.894, 95 % CI 2.31-20.59, P = 0.001). All patients responded well to treatment with no septic complications. Enterococci were the prevalent organism (29.4 %) in patients with a positive SC. Quinolone resistance was high in both gram negative and gram positive bacteria. Patients with an infected stone are at high risk to develop postoperative sepsis despite standard preoperative antibiotic preparation. SC is important to direct further treatment as almost half of patients with positive SC have a discordant or sterile urine culture. Determining the prevalent bacteria and resistance patterns in SC can aid the selection of empiric antibiotic therapy in high-risk patients.
In this study, we estimated the time from first detectable prostate-specific antigen (PSA) follow... more In this study, we estimated the time from first detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) to commonly used definitions of biochemical recurrence (BCR). We also identified the predictors of time to BCR. We identified subjects who underwent a RP and had an undetectable PSA after surgery followed by at least 1 detectable PSA between 2000 and 2011. The primary outcome was time to BCR (PSA ≥0.2 and successive PSA ≥0.2) and prediction of the rate of PSA rise. Outcomes were calculated using a competing risk analysis, with univariable and multivariable Fine and Grey models. We employed a mixed effect model to test clinical predictors that are associated with the rate of PSA rise. The cohort included 376 patients. The median follow-up from surgery was 60.5 months (interquartile range [IQR] 40.8-91.5) and from detectable PSA was 18 months (IQR 11-32). Only 45.74% (n = 172) had PSA values ≥0.2 ng/mL, while 15.16% (n = 57) reached the PSA level of ≥0.4 ng/mL and rising. On multivariable analysis, the values of the first detectable PSA and pathologic Gleason grade 8 or higher were consistently independent predictors of time to BCR. In the mixed effect model rate, the PSA rise was associated with time from surgery to first detectable PSA, Gleason score, and prostate volume. The main limitation of this study is the large proportion of patients that received treatment without reaching BCR. It is plausible that shorter estimated median times would occur at a centre that does not use salvage therapy at such an early state. The time from first detectable PSA to BCR may be lengthy. Our analyses of the predictors of the rate of PSA rise can help determine a personalized approach for patients with a detectable PSA after surgery.
Urologic Oncology: Seminars and Original Investigations, 2014
To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze i... more To identify predictors of the absence of detrusor muscle in bladder tumor specimens and analyze its effect on clinical outcome as an indicator of resection quality. The bladder cancer database of a tertiary medical center was queried for patients who underwent complete transurethral resection of bladder tumor (TURBT) between 2008 and 2009. Study end points were absence of detrusor muscle in the surgical specimen and its association with disease recurrence/progression. Detrusor muscle in the surgical specimen was found in 265 of the 332 study patients (79%). The likelihood of finding muscle increased with higher clinical stage (Odds Ratio [OR]-1.8), higher tumor grade (OR-3), larger tumor size (OR-3.2), multifocal disease (OR-1.7), and nonpapillary morphology (OR-2.3). History of bladder cancer, surgeon's experience, and tumor location in the bladder had no effect. In the whole study population, neither tumor recurrence nor disease progression was associated with absence of detrusor muscle. In patients with T1 tumors, absence of detrusor muscle in the specimen was associated with higher early recurrence rate but not worse long-term outcome. Absence of detrusor muscle in TURBT specimens is not determined by the technical difficulty of the procedure or surgical experience. Surgeons are more prone to obtain deep muscle in large, nonpapillary-appearing tumors, likely reflecting efforts to attain accurate staging in these cases. The presence or absence of detrusor muscle may serve as a surrogate of resection quality in patients with T1 tumors, but its general applicability to the overall population of patients undergoing TURBT remains questionable.
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Papers by David Margel