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1.  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
2.  Regional differences in practice patterns and outcomes in patients treated with radical cystectomy in a universal healthcare system 
Canadian Urological Association Journal  2013;7(11-12):E667-E672.
Introduction
Our objective is to assess differences in practice patterns and outcomes across 3 regions in bladder cancer patients treated with radical cystectomy under a universal healthcare system.
Methods:
In total, we included 2287 patients treated with radical cystectomy at 8 Canadian centres from 1998 to 2008. Variables included various clinico-pathologic parameters, recurrence, and death stratified into different regions.
Results:
In total, 1105 patients were from the east region (group 1), 601 from the centre region (group 2), and 581 from the west region of Canada (group 3). The median follow-up of groups 1, 2, and 3 was 22.1, 17.1, and 28.6 months, respectively. Although the overall rate of neoadjuvant chemotherapy was low (3.1%), rates were higher in group 2 compared with groups 1 and 3 (p = 0.07). Continent diversions and extended lymphadenectomy were performed in 23.5%, 8.5%, 23.9% and 39.7%, 27.7%, 12.6% across groups 1, 2, and 3, respectively. There were statistically significant differences in gender distribution, performance of lymphadenectomy, presence of concomitant carcinoma in situ and lymphovascular invasion across the 3 groups. There were no differences among the 3 geographical locations in terms of stage, surgical margin status, and use of adjuvant chemotherapy. The mean number of days from the transurethral resection of the bladder tumour to cystectomy was 50, 79, 69 days for groups 1, 2, 3, respectively (p = 0.0006). The 5-year overall survival was 53.6%, 66.8%, and 52.4% for groups 1, 2 and 3, respectively (p < 0.0001).
Conclusions:
Significant variations in practice patterns were noted across different geographic regions in a universal healthcare system. Use of continent diversions, extended lymphadenectomy, and neoadjuvant chemotherapy remains low across all 3 regions. Treatment delays are significant.
doi:10.5489/cuaj.201
PMCID: PMC3840506  PMID: 24282454
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
6.  Combining mTOR Inhibition with Radiation Improves Antitumor Activity in Bladder Cancer Cells In Vitro and In Vivo: A Novel Strategy for Treatment 
PLoS ONE  2013;8(6):e65257.
Purpose
Radiation therapy for invasive bladder cancer allows for organ preservation but toxicity and local control remain problematic. As such, improving efficacy of treatment requires radiosensitization of tumor cells. The aim of study is to investigate if the mammalian Target of Rapamycin (mTOR), a downstream kinase of the phosphatidylinositol 3-kinase (PI3K)/AKT survival pathway, may be a target for radiation sensitization.
Experimental Design
Clonogenic assays were performed using 6 bladder cancer cell lines (UM-UC3, UM-UC5, UM-UC6, KU7, 253J-BV, and 253-JP) in order to examine the effects of ionizing radiation (IR) alone and in combination with RAD001, an mTOR inhibitor. Cell cycle analysis was performed using flow cytometry. In vivo, athymic mice were subcutaneously injected with 2 bladder cancer cell lines. Treatment response with RAD001 (1.5 mg/kg, daily), fractionated IR (total 9Gy = 3Gy×3), and combination of RAD001 and IR was followed over 4 weeks. Tumor weight was measured at experimental endpoint.
Results
Clonogenic assays revealed that in all bladder cell lines tested, an additive effect was observed in the combined treatment when compared to either treatment alone. Our data indicates that this effect is due to arrest in both G1 and G2 phases of cell cycle when treatments are combined. Furthermore, our data show that this arrest is primarily regulated by changes in levels of cyclin D1, p27 and p21 following treatments. In vivo, a significant decrease in tumor weight was observed in the combined treatment compared to either treatment alone or control.
Conclusions
Altering cell cycle by inhibiting the mTOR signaling pathway in combination with radiation have favorable outcomes and is a promising therapeutic modality for bladder cancer.
doi:10.1371/journal.pone.0065257
PMCID: PMC3684614  PMID: 23799002
7.  Correction: A Novel Mechanism of PPAR Gamma Induction via EGFR Signalling Constitutes Rational for Combination Therapy in Bladder Cancer 
PLoS ONE  2013;8(5):10.1371/annotation/50295123-3bb7-4916-812c-fa4ea5f09130.
doi:10.1371/annotation/50295123-3bb7-4916-812c-fa4ea5f09130
PMCID: PMC3650997
8.  Human resource assessment of academic urology across Canada: What are the future job prospects? 
Introduction:
Our objective was to capture an overview of anticipated staffing needs at Canadian urology academic centres over the next 5 years to help guide and counsel urology residents in their respective programs.
Methods:
A 30-question survey was sent by email to all chairmen of academic urology divisions/departments during fall 2012. The first part of the survey solicited basic demographic information regarding number of residents, number of fellows and fellowships, and number of attending staff and affiliated hospitals. The second part of the survey included detailed questions on the number and sub-specialty of urologists needed at each respective institution, as well as the appropriate year of recruitment.
Results:
The response rate was 100%. There are 13 urology training programs across Canada located in 6 out of the 10 provinces. Robotic surgery is available at 9 out of the 13 centres. A total of 68 urologists need to be recruited by academic institutions throughout Canada within the next 5 years. The greatest need is for general urologists, with a total of 13 required. This is followed by 12 urologic oncologists needed, 11 female urology, 7 reconstructive urologists, 6 pediatric urologists, 6 endourologists, 5 transplant surgeons, 4 infertility/andrology, and 4 experts in advanced laparoscopy/robotics. There was no need for any urologic trauma surgeons in any academic institution surveyed.
Conclusions:
A total of 68 urologists need to be recruited into academic urology across Canada within the next 5 years. This crucial information can be used to help guide urology residents in choosing the most appropriate fellowship, in addition to providing them with an overview of future job prospects at academic institutions throughout the country.
doi:10.5489/cuaj.198
PMCID: PMC3699074  PMID: 23826042
9.  Risk of cancer-specific mortality following recurrence after radical nephroureterectomy 
Annals of surgical oncology  2012;19(13):4337-4344.
Purpose
To describe the natural history and identify predictors of cancer-specific survival in patients who experience disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).
Methods
Of 2,494 UTUC patients treated with RNU without neoadjuvant chemotherapy, 597 patients experienced disease recurrence. 148 patients (25%) received adjuvant chemotherapy before disease recurrence. Multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence.
Results
The median time from RNU to disease recurrence was 12 months (IQR 5–22). 491 of 597 (82%) patients died from UTUC and 8 patients (1.3%) died from other causes. The median time from disease recurrence to death of UTUC was 10 months. Actuarial cancer-specific survival estimate at 12 months after disease recurrence was 35%. On multivariable analysis that adjusted for the effects of standard clinico-pathologic characteristics, higher tumor stages (HR pT3 vs. pT0-T1: 1.66, p=0.001; HR pT4 vs. pT0-T1: 1.90, p=0.002), absence of lymph node dissection (HR 1.28, p=0.041), ureteral tumor location (HR 1.44, p<0.0005) and a shorter interval from surgery to disease recurrence (p<0.0005) were significantly associated with cancer-specific mortality. The adjusted 6, 12 and 24 months post-recurrence cancer-specific mortality was 73%, 60% and 57%, respectively.
Conclusion
Approximately 80% of patients who experience disease recurrence after RNU die within two years post-recurrence. Patients with non-organ-confined stage, absence of lymph node dissection, ureteral tumor location and/or shorter time to disease recurrence died of their tumor faster than their counterparts. These factors should be considered in patient counseling and risk-stratification for salvage treatment decision-making.
doi:10.1245/s10434-012-2499-8
PMCID: PMC3576920  PMID: 22805867
urothelial carcinoma; upper urinary tract; recurrence; survival; prognosis
10.  A Novel Mechanism of PPAR Gamma Induction via EGFR Signalling Constitutes Rational for Combination Therapy in Bladder Cancer 
PLoS ONE  2013;8(2):e55997.
Background
Two signalling molecules that are attractive for targeted therapy are the epidermal growth factor receptor (EGFR) and the peroxisome proliferator-activated receptor gamma (PPARγ). We investigated possible crosstalk between these 2 pathways, particularly in light of the recent evidence implicating PPARγ for anticancer therapy.
Principal Findings
As evaluated by MTT assays, gefitinib (EGFR inhibitor) and DIM-C (PPARγ agonist) inhibited growth of 9 bladder cancer cell lines in a dose-dependent manner but with variable sensitivity. In addition, combination of gefitinib and DIM-C demonstrated maximal inhibition of cell proliferation compared to each drug alone. These findings were confirmed in vivo, where combination therapy maximally inhibited tumor growth in contrast to each treatment alone when compared to control (p<0.04). Induction of PPARγ expression along with nuclear accumulation was observed in response to increasing concentrations of gefitinib via activation of the transcription factor CCAT/enhancer-binding protein-β (CEBP-β). In these cell lines, DIM-C significantly sensitized bladder cancer cell lines that were resistant to EGFR inhibition in a schedule-specific manner.
Conclusion
These results suggest that PPARγ agonist DIM-C can be an excellent alternative to bladder tumors resistant to EGFR inhibition and combination efficacy might be achieved in a schedule-specific manner.
doi:10.1371/journal.pone.0055997
PMCID: PMC3568080  PMID: 23409107
11.  Extensive renal infarction following percutaneous biopsy of a small renal mass: A case report 
Percutaneous renal biopsy has become increasingly used particularly in patients undergoing active surveillance for small renal masses. We present a patient, who was recently diagnosed with laryngeal squamous cell carcinoma, with significant complication following biopsy of a solid renal mass. The patient was planned for nephron-sparing surgery that was converted to radical nephrectomy due to extensive renal infarction secondary to significant subcapsular hemorrhage inflicted by the biopsy.
doi:10.5489/cuaj.252
PMCID: PMC3650821  PMID: 23671500
13.  Regional differences in practice patterns and associated outcomes for upper tract urothelial carcinoma in Canada 
Introduction:
We delineated Canadian regional differences in practice patterns in the management of upper tract urothelial carcinoma (UTUC) after nephroureterectomy and relate these to patient outcomes.
Methods:
A database was created with 1029 patients undergoing radical nephroureterectomy for UTUC between 1994 and 2009 at 10 Canadian centres. Demographic, clinical and pathological variables were collected from chart review. Practice pattern variables were defined as: open versus laparoscopic nephroureterectomy, management strategy for the distal ureter, performance of lymphadenectomy and administration of chemotherapy and/or radiation therapy. The outcome measures were overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). The centres were divided into three regions (West, Central, East). Cox proportional multivariable linear regression analysis was used to determine the association between regional differences in practice patterns and clinical outcomes.
Results:
There was a significant difference in practice patterns between regions within Canada for: time from diagnosis to surgery (p = 0.001), type of surgery (open vs. laparoscopic, p < 0.01) and method of management of the distal ureter (p = 0.001). As well, there were significant differences in survival between regions across Canada: 5-year OS (West 70%, Central 81% and East 62%, p < 0.0001) and DSS (West=79%, Central=85%, East=75%, p = 0.007) were significantly different, but there was no difference in RFS (West 47%, Central 48%, East 46%, p = 0.88). Multivariable linear regression analysis demonstrated that the differences in survival were independent of region OS (p = 0.78), DSS (p = 0.30) or RFS (p = 0.43).
Conclusion:
There is significant disparity in practice patterns between regions within Canada, but these do not appear to have an effect on survival. We believe that the variability in practice is a reflection of the lack of standardized treatments for UTUC and underlines the need for multi-institutional studies in this disease.
doi:10.5489/cuaj.12146
PMCID: PMC3526631  PMID: 23282664
14.  Natural history of pT3-4 or node positive bladder cancer treated with radical cystectomy and no neoadjuvant chemotherapy in a contemporary North-American multi-institutional cohort 
Background:
The present study documents the natural history and outcomes of high-risk bladder cancer after radical cystectomy (RC) in patients who did not receive neoadjuvant chemotherapy during a contemporary time period.
Methods:
We analyzed 1180 patients from 1993 to 2008 with >pT3N0 or pT0-4N+ bladder cancer who underwent RC ± standard (sLND) or extended (eLND) lymph node dissection from 8 Canadian centres.
Results:
Of the 1180 patients, 55% (n = 643) underwent sLND, 34% (n = 402) underwent ePLND and 11% did not undergo a formal LND. Of the total number of patients, 321 (27%) received adjuvant chemotherapy. The median follow-up was 2.1 years (range: 0.6 to 12.9). Overall 30-day mortality was 3.2%. Clinical and pathological stages T3-4 were present in 6.1% and 86.7% of the patients, respectively; this demonstrates a dramatic understaging. Overall survival (OS) at 2 and 5 years was 60% and 43%, respectively. Patients who received adjuvant chemotherapy had a 2- and 5-year disease-specific survival (DSS) of 72% and 57% versus 64% and 51% for those who did not (log-rank p = 0.0039). The 2- and 5-year OS for high-risk node-negative disease was 67% and 52%, respectively, whereas for node-positive patients, the OS was 52% and 32%, respectively (p < 0.001). The OS, DSS and RFS for patients with pN0 were significantly improved compared to those who did not undergo a LND (log-rank p = 0.0035, 0.0241 and 0.0383, respectively).
Interpretation:
This series suggests that bladder cancer outcomes in advanced disease have improved in the modern era. The need for improved staging investigations, use of neoadjuvant chemotherapy and performance of complete LND is emphasized.
doi:10.5489/cuaj.11012
PMCID: PMC3529724  PMID: 23283097
15.  Outcomes of pT0N0 at radical cystectomy: The Canadian Bladder Cancer Network experience 
Introduction:
Radical cystectomy is the standard treatment for muscle invasive bladder cancer. We assessed clinical outcomes in patients found to have no evidence of disease (i.e., pT0N0) following radical cystectomy.
Methods:
We collected and pooled a database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in eight centres across Canada. Of this number, 135 patients were found to have pT0N0 bladder cancer at the time of cystectomy. Survival data and prognostic variables were analyzed using Kaplan-Meier method and Cox proportional hazard regression analysis.
Results:
Median patient age was 66 years with a mean follow-up of 42 months. Clinical stage distribution was Tis 8.9%, Ta 1.5%, T1 20.7%, T2 45.2%, T3 5.2%, and T4 5.2%. The five-year recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were 83%, 96%, and 88%, respectively. The 10-year RFS, DSS and OS were 66%, 92%, and 70%, respectively. On Cox proportional regression analysis, no variables were associated with disease recurrence and only patient age was associated with overall survival.
Interpretation:
Patients with pT0N0 pathology after cystectomy have excellent outcomes with high five- and 10-year RFS, DSS and OS. However, there is still a risk of tumour recurrence in this patient population and thus postoperative surveillance is still required.
doi:10.5489/cuaj.11276
PMCID: PMC3377737  PMID: 22709882
17.  The Role of Radical Cystectomy in Patients with Clinical T4b Bladder Cancer 
Urologic oncology  2010;29(2):157-161.
SUMMARY
Objectives
Patients with clinical T4b bladder cancer (extension to pelvic wall and/or adjacent organs other than prostate, vagina or uterus) are commonly considered unresectable. We hypothesized that select patients might achieve durable benefit from multiagent chemotherapy and extirpative surgery.
Methods
We identified patients with clinical T4bN0 bladder cancer from our IRB-approved database of patients undergoing radical cystectomy (n =1194). Relevant demographic, clinical and pathologic data were compiled. Overall (OS), disease-specific (DSS) and recurrence-free survival (RFS) were analyzed by Kaplan-Meier estimation. Cox proportional hazards regression modeling was used to evaluate the influence of several potential prognostic factors.
Results
Twenty-three patients (16 male) with a median age of 65 years met study criteria. Chemotherapy was administered pre-operatively to 19 (83%) and post-operatively to 8 (35%) patients. Eight patients died of disease and one of other causes. The 1-, 2- and 5-year DSS was 91% (95% C.I. 70–98%), 66% (95% C.I. 42–83%) and 60% (95% C.I. 34–78%), respectively. Eight of 17 patients with pT2-4 tumors succumbed to disease compared to none of 6 who were ≤ pT1 (p=0.04). Other predictors of decreased DSS included positive surgical margins (HR=5.34, 95% C.I. 1.25–22.83) and presence of pathologic nodal metastasis (HR=29.33, 95% C.I. 3.13–275.19). Variant histology was more common in this cohort than in the overall cystectomy database (43% vs. 11%).
Conclusions
Long-term survival can be achieved in a proportion of patients with cT4b bladder cancer undergoing chemotherapy and extirpative surgery. Careful selection of patients and meticulous surgical technique to avoid positive margins are critical.
doi:10.1016/j.urolonc.2009.12.015
PMCID: PMC2950900  PMID: 20456984
bladder cancer; cystectomy; chemotherapy
19.  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
20.  Radical cystectomy for the treatment of T1 bladder cancer: the Canadian Bladder Cancer Network experience 
Background:
Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system.
Methods:
We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis.
Results:
The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival.
Interpretation:
These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies.
doi:10.5489/cuaj.10040
PMCID: PMC3104425  PMID: 21470529
21.  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
23.  Lymphovascular Invasion Predicts Clinical Outcomes in Patients With Node-Negative Upper Tract Urothelial Carcinoma 
Journal of Clinical Oncology  2008;27(4):612-618.
Purpose
To assess the association of lymphovascular invasion (LVI) with cancer recurrence and survival in a large international series of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC).
Patients and Methods
Data were collected on 1,453 patients treated with RNU at 13 academic centers and combined into a relational database. Pathologic slides were rereviewed by genitourinary pathologists according to strict criteria. LVI was defined as presence of tumor cells within an endothelium-lined space.
Results
LVI was observed in 349 patients (24%). Proportion of LVI increased with advancing tumor stage, high tumor grade, presence of tumor necrosis, sessile tumor architecture, and presence of lymph node metastasis (all P < .001). LVI was an independent predictor of disease recurrence and survival (P < .001 for both). Addition of LVI to the base model (comprising pathologic stage, grade, and lymph node status) marginally improved its predictive accuracy for both disease recurrence and survival (1.1%, P = .03; and 1.7%, P < .001, respectively). In patients with negative lymph nodes and those in whom a lymphadenectomy was not performed (n = 1,313), addition of LVI to the base model improved the predictive accuracy of the base model for both disease recurrence and survival by 3% (P < .001 for both). In contrast, LVI was not associated with disease recurrence or survival in node-positive patients (n = 140).
Conclusion
LVI was an independent predictor of clinical outcomes in nonmetastatic patients who underwent RNU for UTUC. Assessment of LVI may help identify patients who could benefit from multimodal therapy after RNU. After confirmation, LVI should be included in staging of UTUC.
doi:10.1200/JCO.2008.17.2361
PMCID: PMC2737380  PMID: 19075275
24.  Update on the management of non-muscle invasive bladder cancer 
Non-muscle invasive bladder cancer (NMIBC) is a heterogeneous population of tumours accounting for 80% of bladder cancers. Over the years, the management of this disease has been changing with improvements in results and outcomes. In this review, we focus on the latest updates on the management of NMIBC.
PMCID: PMC2812001  PMID: 20165581
25.  OUTCOME OF BLADDER CANCER PATIENTS WITH pN+ DISEASE AFTER PREOPERATIVE CHEMOTHERAPY AND RADICAL CYSTECTOMY 
Urology  2008;73(1):147-152.
Objectives
Persistent nodal disease in the surgical specimen (pN+) after preoperative chemotherapy for urothelial carcinoma (UC) is associated with poor prognosis. To improve our understanding regarding outcome of such patients, we performed a retrospective review of our experience.
Methods
Between 1993–2003, 857 patients underwent radical cystectomy for UC of the bladder, and 150 were found to be pN+. Of these, 37 were pN+ despite preoperative chemotherapy and form the basis of this report. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis.
Results
The patients’ median age was 66 years (range 39 to 85 years), and the median follow-up was 50 months (range 13.0 to 58.7 months). Clinical stages (at time of initiation of preoperative chemotherapy) were cT2 with lymphovascular invasion: 7, cT3b: 6, cT4a: 4, cT4b: 2, and cN+: 18. The 2-year overall (OS), disease-specific (DSS), and recurrence-free (RFS) survival rates were 20%, 29.2%, and 13.5%, respectively. Eleven (30%) patients received adjuvant chemotherapy after surgery; majority (73%) were platinum-based regimens. On multivariate analysis, surgical margin status, gender, and histology were significantly associated with OS, and histology and use of adjuvant chemotherapy were significantly associated with RFS.
Conclusion
Patients who have persistent nodal disease despite preoperative chemotherapy have a poor prognosis. A cohort of such patients may do well with adjuvant chemotherapy. Lymph node density and pT stage are not prognostic in patients with nodal metastasis after preoperative chemotherapy.
doi:10.1016/j.urology.2008.07.035
PMCID: PMC2674246  PMID: 18848348

Results 1-25 (41)