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1.  Growth kinetics of small renal masses: A prospective analysis from the Renal Cell Carcinoma Consortium of Canada 
Introduction:
Most small renal masses (SRMs) are diagnosed incidentally and have a low malignant potential. As more elderly patients and infirm patients are diagnosed with SRMs, there is an increased interest in active surveillance (AS) with delayed intervention. Patient and tumour characteristics relating to aggressive disease have not been well-studied. The objective was to determine predictors of growth of SRMs treated with AS.
Methods:
A multicentre prospective phase 2 clinical trial was conducted on 207 SRMs in 169 patients in 8 institutions in Canada from 2004 to 2009; in these patients treatment was delayed until disease progression. Patient and tumour characteristics were evaluated to determine predictors of growth of SRMs by measuring rates of change in growth (on imaging) over time. All patients underwent AS for presumed renal cell carcinoma (RCC) based on diagnostic imaging. We used the following factors to develop a predictive model of tumour growth with binary recursive partitioning analysis: patient characteristics (age, symptoms at diagnosis) and tumour characteristics (consistency [solid vs. cystic] and maximum diameter at diagnosis.
Results:
With a median follow-up of 603 days, 169 patients (with 207 SRMs) were followed prospectively. Age, symptoms at diagnosis, tumour consistency and maximum diameter of the renal mass were not predictors of growth. This cohort was limited by lack of availability of patient and tumour characteristics, such as sex, degree of endophytic component and tumour location.
Conclusion:
Slow growth rates and the low malignant potential of SRMs have led to AS as a treatment option in the elderly and infirm population. In a large prospective cohort, we have shown that age, symptoms, tumour consistency and maximum diameter of the mass at diagnosis are not predictors of growth of T1a lesions. More knowledge on predictors of growth of SRMs is needed.
doi:10.5489/cuaj.1483
PMCID: PMC3929474  PMID: 24578738
2.  Aldehyde dehydrogenase 1 expression in primary and metastatic renal cell carcinoma: an immunohistochemistry study 
Background
ALDH1 has been shown to be a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. We aimed to evaluate the expression of ALDH1 in a cohort of primary and metastatic RCC specimens, and to correlate expression with pathological outcomes such as tumor stage and grade, and clinical outcomes such as progression free survival.
Methods
Three tissue microarrays were constructed from 244 RCC specimens, taken from 1985 to 2006. Samples were stained using an ALDH1 monoclonal antibody and expression was quantified by degree of staining. Membrane and cytoplasm staining were considered separately. A retrospective chart review enabled correlation with clinical outcomes.
Results
ALDH1 expression did not vary significantly based on tumor stage (P = 0.6274) or grade (P = 0.1666). ALDH1 showed significantly more membranous expression in clear cell RCC versus other subtypes (P < 0.0001), as well as in the primary setting compared to metastases (P = 0.0216). In terms of progression free survival, no significant differences were seen based on ALDH1 expression levels. In a subanalysis of clear cell tumors, ALDH1 membranous expression was decreased in tumors of higher stage (P = 0.0233).
Conclusions
ALDH1 may be useful in characterizing RCC tumors as clear cell subtype. However, unlike in other malignancies, ALDH1 may not be useful in prognosticating renal cancers. The clinical significance of decreased ALDH1 expression in the high stage and metastatic setting remains to be determined in further investigations.
doi:10.1186/1477-7819-11-298
PMCID: PMC3842840  PMID: 24266898
ALDH1; Renal cell carcinoma; Prognosis; Immunohistochemistry
3.  Does transperitoneal minimally invasive radical prostatectomy increase the amount of small bowel receiving salvage radiation? 
Introduction:
Transperitoneal minimally invasive radical prostatectomy (MIRP) has become first choice for several urologists and patients dealing with localized prostate cancer. We evaluate the effect of postoperative radiation on the small bowel in patients who underwent extraperitoneal open versus transperitoneal MIRP.
Methods:
We reviewed all patients who received postoperative radiation from 2006 to 2010. Planning target volume (PTV) and surrounding organs, including the small bowel, were delineated. The presence of the small bowel in PTV and its volume in receiving each dose level were analyzed.
Results:
A total of 122 patients were included: 26 underwent MIRP and 96 underwent open prostatectomy. The median age of patients was 66 years, with median body mass index 27 kg/m2. The total PTV dose was 66 Gy, with the minimum and maximum doses received by the small bowel 0.4 and 66.4 Gy, respectively. The maximum volume of small bowel that received the safe limit of 40 Gy was 569 cm3. Of the 26 patients who underwent MIRP, 12 (46%) had small bowel identified inside the PTV compared to 57 (59%) among patients who underwent open prostatectomy (p = 0.228). The mean volume of the small bowel receiving 40 Gy was 26 and 67 cm3 in open and MIRP groups, respectively (p = 0.006); the incidence of acute complications was the same in both groups.
Conclusions:
Higher volumes of the small bowel are subjected to significant radiation after MIRP procedures compared to open procedures; however, we could not demonstrate any impact on acute complications. Whether there is a difference in late complications remains to be evaluated.
doi:10.5489/cuaj.265
PMCID: PMC3876447  PMID: 24381666
4.  Canadian guideline on genetic screening for hereditary renal cell cancers 
Background:
Hereditary renal cell cancer (RCC) is an ideal model for germline genetic testing. We propose a guideline of hereditary RCC specific criteria to suggest referral for genetic assessment.
Methods:
A review of the literature and stakeholder resources for existing guidelines or consensus statements was performed. Referral criteria were developed by expert consensus.
Results:
The criteria included characteristics for patients with RCC (age ≤45 years, bilateral or multifocal tumours, associated medical conditions and non-clear cell histologies with unusual features) and for patients with or without RCC, but a family history of specific clinical or genetic diagnoses.
Conclusions:
This guideline represents a practical RCC-specific reference to allow healthcare providers to identify patients who may have a hereditary RCC syndrome, without extensive knowledge of each syndrome. RCC survivors and their families can also use the document to guide their discussions with healthcare providers about their need for referral. The criteria refer to the most common hereditary renal tumour syndromes and do not represent a comprehensive or exclusive list. Prospective validation of the criteria is warranted.
doi:10.5489/cuaj.1496
PMCID: PMC3854468  PMID: 24319509
5.  Patients with microscopic and gross hematuria: practice and referral patterns among primary care physicians in a universal health care system 
Background:
Hematuria is one of the most common findings on urinalysis in patients encountered by primary care physicians. In many instances it can also be the first presentation of a serious urological problem. As such, we sought to evaluate current practices adopted by primary care physicians in the workup and screening of hematuria.
Methods:
Questionnaires were mailed to all registered primary care physicians across Quebec. Questions covered each physician’s personal approach to men and postmenopausal women with painless gross hematuria or with asymptomatic microscopic hematuria, as well as screening techniques, general knowledge with regards to urine collection and sampling, and referral patterns.
Results:
Of the surveys mailed, 599 were returned. Annual routine screening urinalysis on all adult male and female patients was performed by 47% of respondents, regardless of age or risk factors. Of all the respondents, 95% stated microscopic hematuria was associated with bladder cancer. However, in an older male with painless gross hematuria, only 64% of respondents recommended further evaluation by urology. On the other hand, in a postmenopausal woman with 2 consecutive events of significant microscopic hematuria, only 48.6% recommended referral to urology. Findings were not associated with the gender of the respondent, experience or geographic location of practice (urban vs. rural).
Interpretation:
There seems to be reluctance amongst primary care physicians to refer patients with gross or significant microscopic hematuria to urology for further investigation. A higher level of suspicion and further education should be implemented to detect serious conditions and to offer earlier intervention when possible.
doi:10.5489/cuaj.10059
PMCID: PMC3104421  PMID: 21470533
6.  Retroperitoneal lymph node dissection for residual masses after chemotherapy in nonseminomatous germ cell testicular tumor 
Background
Retroperitoneal lymph node dissection has been advocated for the management of post-chemotherapy (PC-RPLND) residual masses of non-seminomatous germ cell tumors of the testis (NSGCT). There remains some debate as to the clinical benefit and associated morbidity. Our objective was to report our experience with PC-RPLND in NSGCT.
Methods
We have reviewed the clinical, pathologic and surgical parameters associated with PC-RPLND in a single institution. Between 1994 and 2008, three surgeons operated 73 patients with residual masses after cisplatin-based chemotherapy for a metastatic testicular cancer. Patients needed to have normal postchemotherapy serum tumor markers, no prior surgical attempts to resect retroperitoneal masses and resectable retroperitoneal tumor mass at surgery to be included in this analysis
Results
Mean age was 30.4 years old. Fifty-three percent had mixed germ cell tumors. The mean size of retroperitoneal metastasis was 6.3 and 4.0 cm, before and post-chemotherapy, respectively. In 56% of patients, the surgeon was able to perform a nerve sparing procedure. The overall complication rate was 27.4% and no patient died due to surgical complications. The pathologic review showed presence of fibrosis/necrosis, teratoma and viable tumor (non-teratoma) in 27 (37.0%), 30 (41.1%) and 16 (21.9%) patients, respectively. The subgroups presenting fibrosis and large tumors were more likely to have a surgical complication and had less nerve sparing procedures.
Conclusion
PC-RPLND is a relatively safe procedure. The presence of fibrosis and large residual masses are associated with surgical complications and non-nerve-sparing procedure.
doi:10.1186/1477-7819-8-97
PMCID: PMC2991320  PMID: 21062470
8.  Diagnosis and management of benign prostatic hyperplasia in primary care 
Canadian Urological Association Journal  2009;3(3 Suppl 2):S92-S100.
Benign prostatic hyperplasia (BPH), and its clinical manifestation as lower urinary tract symptoms (LUTS), is a major health concern for aging men. There have been significant advances in the diagnosis and treatment of BPH in recent years. There has been a renewed interest in medical therapies and less invasive surgical techniques. As a consequence, the treatment needs of men with mild to moderate LUTS without evidence of prostate cancer can now be accomplished in a primary care setting. There are differences in the way urologists and primary care physicians approach the evaluation and management of LUTS due to BPH, which is not reflected in Canadian Urological Association (CUA) and American Urological Association (AUA) guidelines. A “shared care” approach involving urologists and primary care physicians represents a reasonable and viable model for the care of men suffering from LUTS. The essence of the model centres around educating and communicating effectively with the patient on BPH. This article provides primary care physicians with an overview of the diagnostic and management strategies outlined in recent CUA and AUA guidelines so that they may be better positioned to effectively deal with this patient population. It is now apparent that we must move away from the urologist as the first-line physician, and allow primary care physicians to accept a new role in the diagnosis and management of BPH.
PMCID: PMC2698785  PMID: 19543429
10.  Primary renal carcinoid tumour with inferior vena caval tumour thrombus 
Carcinoid tumours, most frequently reported in the gastrointestinal and respiratory tracts, are exceedingly rare primary renal cancers. Few cases have been published to date. To our knowledge, we report the first case of a primary carcinoid tumour of the kidneys involving the inferior vena cava. We treated a 58-year-old woman with an open radical nephrectomy and cavotomy with thrombectomy. We describe the presentation, investigations and pathology results. We discuss the current experience with carcinoid tumours as a literature review relating to the diagnosis of the disease and the prognosis of patients with this neoplasm. Localized carcinoid tumours of the kidneys, including those involving the vena cava, can be successfully treated with surgical excision.
PMCID: PMC2692164  PMID: 19543456
11.  Impact of treatment delay in patients with bladder cancer managed with partial cystectomy in Quebec: a population-based study 
Objective
Treatment delays have been associated with adverse outcomes in patients with bladder cancer treated with radical cystectomy (RC). We sought to evaluate the impact of treatment delay on disease recurrence and survival in patients with bladder cancer treated with partial cystectomy (PC) in Quebec.
Methods
We reviewed and obtained billing records for all patients who underwent PC and/or RC for bladder cancer in Quebec between 1983 and 2005. Analysis included age, sex, year of surgery, surgeon’s age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of death.
Results
A total of 714 patients underwent PC. The median patient age was 70 years. Two-hundred nineteen (30.7%) patients experienced recurrence; of these, 52 (23.7%) required salvage RC. Five-year overall and recurrence-free survival for patients who underwent PC were 49.8% and 40.3%, respectively. Patients delayed more than 12 weeks from transurethral resection of bladder tumours (TURBT) to PC were at significantly increased risk of requiring salvage RC compared with those delayed 12 weeks or less (hazard ratio [HR] 3.0, p < 0.001). Patients who underwent salvage RC had worse survival than patients who had upfront RC (HR 1.5, p = 0.006). Variables including age, sex, presence of hematuria, intravesical therapy, surgeon age, hospital PC volume, surgeon PC volume, type of hospital (academic v. nonacademic) or year of surgery were not significantly associated with PC treatment delay.
Conclusion
Treatment delay in patients with bladder cancer managed with PC was associated with increased risk of salvage RC. Patients with bladder cancer who underwent salvage RC had worse outcomes than those who had upfront cystectomy.
PMCID: PMC2666899  PMID: 19424467
13.  Dietary habits and prostate cancer detection: a case–control study 
Background
Many studies have suggested that nutritional factors may affect prostate cancer development. The aim of our study was to evaluate the relationship between dietary habits and prostate cancer detection.
Methods
We studied 917 patients who planned to have transrectal ultrasonography–guided prostatic biopsy based on an elevated serum prostate-specific antigen (PSA) level, a rising serum PSA level or an abnormal digital rectal examination. Before receiving the results of their biopsy, all patients answered a self-administered food frequency questionnaire. In combination with pathology data we performed univariable and multivariable logistic regression analyses for the predictors of cancer and its aggressiveness.
Results
Prostate cancer was found in 42% (386/917) of patients. The mean patient age was 64.5 (standard deviation [SD] 8.3) years and the mean serum PSA level for prostate cancer and benign cases, respectively, was 13.4 (SD 28.2) μg/L and 7.3 (SD 4.9) μg/L. Multivariable analysis revealed that a meat diet (e.g., red meat, ham, sausages) was associated with an increased risk of prostate cancer (odds ratio [OR] 2.91, 95% confidence interval [CI] 1.55–4.87, p = 0.027) and a fish diet was associated with less prostate cancer (OR 0.54, 95% CI 0.32–0.89, p = 0.017). Aggressive tumours were defined by Gleason score (≥ 7), serum PSA level (≥ 10 μg/L) and the number of positive cancer cores (≥ 3). None of the tested dietary components were found to be associated with prostate cancer aggressivity.
Conclusion
Fish diets appear to be associated with less risk of prostate cancer detection, and meat diets appear to be associated with a 3-fold increased risk of prostate cancer. These observations add to the growing body of evidence suggesting a relationship between diet and prostate cancer risk.
PMCID: PMC2572247  PMID: 18953447
14.  An analysis of preoperative delays prior to radical cystectomy for bladder cancer in Quebec 
Background
The province of Quebec has the highest incidence of urothelial tumours in Canada. Radical cystectomy remains the standard treatment for invasive bladder cancer. We have previously observed that prolonged delays between transurethral resection of bladder tumour (TURBT) and radical cystectomy lead to worse survival in Quebec.
Objective
The aim of our study was to characterize the various periods of delay sustained by bladder cancer patients before radical cystectomy across Quebec and to determine their relation to survival.
Methods
We obtained the billing records for all patients treated with radical cystectomies for bladder cancer across Quebec from 1990 to 2002. Collected information included patient age and sex; dates of family physician (FP) and specialist visits with accompanying diagnoses; dates of cystoscopy, TURBT and CT scanning; surgeon age; surgical volume and dates of death.
Results
We analyzed a total of 25 862 visits for 1633 patients. Median diagnostic delays from FP to specialist, then to cystoscopy, then to TURBT and finally from TURBT to CT were 20, 11, 4 and 14 days, respectively, over the entire study period. Median overall delay from FP visit to radical cystectomy was 93 days. In addition, median FP to radical cystectomy delay progressively increased from 1990 to 2000 from 58 to 120 days (p < 0.01). Multivariate analyses showed that patients with an overall delay of either < 25 or > 84 days had a 2.1 and 1.4 times increased risk of dying, respectively (p ≤ 0.01).
Conclusion
Preoperative delays have been progressively increasing over time. Overall, delays from FP to radical cystectomy of < 25 and > 84 days may translate into worse outcomes. Poor survival in cases with < 25 days delay may be attributed to case selection, with more advanced cases being managed much quicker. Poor survival in cases with delays of > 84 days may be attributed to disease progression while awaiting completion of management.
PMCID: PMC2422906  PMID: 18542741
15.  DEVELOPMENT AND VALIDATION OF A NOMOGRAM PREDICTING THE OUTCOME OF PROSTATE BIOPSY BASED ON PATIENT AGE, DIGITAL RECTAL EXAMINATION AND SERUM PROSTATE SPECIFIC ANTIGEN 
The Journal of urology  2005;173(6):1930-1934.
Purpose
We developed and validated a nomogram which predicts presence of prostate cancer (PCa) on needle biopsy.
Materials and Methods
We used 3 cohorts of men who were evaluated with sextant biopsy of the prostate and whose presenting prostate specific antigen (PSA) was not greater than 50 ng/ml. Data from 4,193 men from Montreal, Canada were used to develop a nomogram based on age, digital rectal examination (DRE) and serum PSA. External validation was performed on 1,762 men from Hamburg, Germany. Data from these men were subsequently used to develop a second nomogram in which percent free PSA (%fPSA) was added as a predictor. External validation was performed using 514 men from Montreal. Both nomograms were based on multivariate logistic regression models. Predictive accuracy was evaluated with areas under the receiver operating characteristic curve and graphically with loess smoothing plots.
Results
PCa was detected in 1,477 (35.2%) men from Montreal, 739 (41.9%) men from Hamburg and 189 (36.8%) men from Montreal. In all models all predictors were significant at 0.05. Using age, DRE and PSA external validation AUC was 0.69. Using age, DRE, PSA and %fPSA external validation AUC was 0.77.
Conclusions
A nomogram based on age, DRE, PSA and %fPSA can highly accurately predict the outcome of prostate biopsy in men at risk for PCa.
doi:10.1097/01.ju.0000158039.94467.5d
PMCID: PMC1855288  PMID: 15879784
prostatic neoplasms; biopsy; nomograms; validation studies
16.  Subsequent prostate cancer detection in patients with prostatic intraepithelial neoplasia or atypical small acinar proliferation 
Introduction:
To evaluate the predictors of prostate cancer in follow-up of patients diagnosed on initial biopsy with high-grade prostatic intraepithelial neoplasia (HGPIN) or atypical small acinar proliferation (ASAP).
Methods:
We studied 201 patients with HGPIN and 22 patients with ASAP on initial prostatic biopsy who had subsequent prostatic biopsies. The mean time of follow-up was 17.3 months (range 1–62). The mean number of biopsy sessions was 2.5 (range 2–6), and the median number of biopsy cores was 10 (range 6–14).
Results:
On subsequent biopsies, the rate of prostate cancer was 21.9% (44/201) in HGPIN patients. Of these, 32/201 patients (15.9%), 9/66 patients (13.6%) and 3/18 patients (16.6%) were found to have cancer on the first, second and third follow-up biopsy sessions, respectively. In ASAP patients, the cancer detection rate was 13/22 (59.1%), all of whom were found on the first follow-up biopsy. There was a statistically significant difference between the cancer detection rate in ASAP and HGPIN patients (p < 0.001). Multivariate analysis showed that the independent predictors of cancer were the number of cores in the initial biopsy, the number of cores (> 10) in the follow-up biopsy and a prostate specific antigen (PSA) density of ≥ 0.15 (odds ratio 0.77, 3.46 and 2.7,8 respectively; p < 0.04). Conversely, in ASAP patients none of these variables were found to be associated with cancer diagnosis.
Conclusion:
ASAP is a strong predictive factor associated with cancer when compared with HGPIN. The factors predictive of cancer on follow-up biopsy of HGPIN are number of cores on initial biopsy, more than 10 cores in rebiopsy and elevated PSA density. As the cancer detection rate on repeated biopsy of HGPIN patients is the same as that of patients without HGPIN, perhaps the standard of repeat biopsy in all patients with HGPIN should be revisited.
PMCID: PMC2422970  PMID: 18542796
17.  Locally advanced renal cell carcinoma 
Canadian Urological Association Journal  2007;1(2 Suppl):S55-S61.
Despite the observed stage migration and earlier detection of renal masses, patients still present with locally advanced renal cell carcinoma. These patients represent a difficult oncologic challenge. Despite our ability to do surgical resection to cure the disease, survival often remains limited. In this paper, we describe the role and indication for surgical resection for patients with enlarged retroperitoneal lymph nodes, invasion of adjacent organs, invasion into the vena cava or locally recurrent disease. The development of new strategies, including effective drugs to be used in association with surgical resection, will clearly be an essential step to further improve the outcome of these patients.
PMCID: PMC2422948  PMID: 18542785

Results 1-17 (17)