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1.
J Urol ; 193(3): 869-74, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25261806

ABSTRACT

PURPOSE: We examined temporal changes in the demographics of patients undergoing definitive treatment for kidney stones during a 20-year period in Ontario, Canada. MATERIALS AND METHODS: Using the Ontario Health Insurance Plan physician claims database and the Canadian Institute for Health Information Discharge Abstract Database we performed a population based cross-sectional time series analysis by identifying all kidney stone treatments done between July 1, 1991 and December 31, 2010. The demographics assessed were patient gender, age and socioeconomic status. The rate and/or proportion of kidney stone treatments per strata of these demographics were calculated for each 1-year block of the study period. We used time series analysis with exponential smoothing and autoregressive integrated moving average models to assess for trends with time. RESULTS: We identified 116,115 patients who underwent treatment for kidney stones during the study period. The rate of stone procedures performed per year increased steadily from 85/100,000 to 126/100,000 population. With time the rate of females who were treated increased significantly from 40/100,000 to 53/100,000 (p <0.0001). In contrast, the rate of males who were treated remained stable, increasing from 82/100,000 to 83/100,000 (p = 0.11). In regard to age the rate of patients older than 64 years increased significantly with time from 67/100,000 to 89/100,000 (p <0.0001). In regard to socioeconomic status approximately 20% of the patients were in each of the 5 income quintiles during the entire study period. CONCLUSIONS: Our population based study shows an increased rate of females and of patients older than 64 years undergoing definitive treatment for kidney stones with time.


Subject(s)
Kidney Calculi/epidemiology , Kidney Calculi/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Ontario/epidemiology , Research Design , Time Factors , Young Adult
2.
Mol Cell Proteomics ; 12(1): 132-44, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23082029

ABSTRACT

Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies, and patients have a dismal prognosis, with a <10% five-year survival rate. The identification of markers that can predict the potential for metastases will have a great effect in improving patient outcomes. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic and primary RCC. We identified 1256 non-redundant proteins, and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 underexpressed) in metastatic and primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14-3-3 zeta/delta (14-3-3ƎĀ¶), and galectin-1 (Gal-1) were verified on two independent sets of tissues by means of Western blot and immunohistochemical analysis. Hierarchical clustering analysis showed that the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14-3-3ƎĀ¶ and Gal-1 also showed higher expression in tumors with poor prognosis than in those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients, and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC.


Subject(s)
Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Neoplasm Proteins/analysis , Proteome/analysis , 14-3-3 Proteins/metabolism , Biomarkers, Tumor/analysis , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/secondary , Chromatography, Liquid , Disease Progression , Galectin 1/metabolism , Gene Expression , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Neoplasm Metastasis , Profilins/metabolism , Prognosis , Proteomics , Tandem Mass Spectrometry
3.
J Urol ; 192(5): 1450-6, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24866599

ABSTRACT

PURPOSE: We evaluate population based trends in the use of extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy during the last 20 years, as well as assess the re-treatment rate and morbidity from treatment over time. MATERIALS AND METHODS: Using administrative databases in the province of Ontario, Canada, a population based cross-sectional time series analysis was performed between July 1, 1991 and December 31, 2010. All extracorporeal shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy procedures were identified, along with all hospital readmissions and emergency department visits within 7 days of treatment. The primary outcome was treatment use, andĀ secondary outcomes were the need for ancillary treatment and hospital readmission or emergency department visit after treatment. Exponential smoothing and autoregressive integrated moving average (ARIMA) models were used to assess trends over time. RESULTS: We identified 194,781 kidney stone treatments performed during the study period. Time series modeling revealed a significant increase in the use of ureteroscopy over time (25% to 59% of all procedures, p <0.0001) and a reciprocal decrease in the use of extracorporeal shock wave lithotripsy (69% to 34% of all procedures, p <0.0001). A corresponding significant decrease in the need for ancillary treatment over time (23% to 15%, p <0.0001) and increase in the need for hospital readmission (7% to 11%, p <0.0001) or emergency department visit (7% to 11%, p=0.0024) after treatment were also demonstrated. CONCLUSIONS: Our population based study demonstrates a shift in the treatment paradigm with increased use of ureteroscopy over time and a reciprocal decrease in the use of extracorporeal shock wave lithotripsy. We also observed a corresponding decrease in ancillary treatment and increase in posttreatment morbidity over time.


Subject(s)
Kidney Calculi/surgery , Lithotripsy/methods , Nephrostomy, Percutaneous/methods , Population Surveillance/methods , Postoperative Complications/epidemiology , Ureteroscopy/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Ontario/epidemiology , Prognosis , Retrospective Studies , Treatment Outcome , Young Adult
4.
Prog Transplant ; 24(4): 322-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25488553

ABSTRACT

OBJECTIVE: To evaluate the role of prophylactic versus selective ureteric stenting in the development of postoperative ureterovesical complications in kidney transplant recipients. METHODS: Records of 614 transplant patients seen from January 2006 to May 2011 were retrospectively reviewed. The primary outcome was the rate of ureterovesical complications, defined as the development of ureteric obstruction or a ureterovesical anastomotic leak. The secondary outcomes were the rate of urinary tract infections and forgotten stents. Using a χ2 test, we compared the primary and secondary outcomes across the selective and prophylactic cohorts. Logistic regression was used to compare the 2 cohorts while adjusting for potential confounders. RESULTS: The selective and prophylactic cohorts consisted of 258 and 330 patients, respectively. Unadjusted analysis showed that the prophylactic group had a significantly lower rate of ureterovesical complications than did the selective group (2.12% vs 6.20%; odds ratio, 0.33; P= .01). After adjustment for differences in sex and donor type, the prophylactic group still had a lower risk for ureterovesical complications (odds ratio, 0.30; P= .009). Rates of urinary tract infections and forgotten stents did not differ significantly between the 2 groups. CONCLUSIONS: Prophylactic stenting is associated with a significantly lower rate of ureterovesical complications than is selective stenting.


Subject(s)
Postoperative Complications/prevention & control , Stents , Urologic Diseases/prevention & control , Female , Humans , Kidney Transplantation , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Ureter/surgery
5.
Can Urol Assoc J ; 18(3): E59-E64, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38010221

ABSTRACT

INTRODUCTION: At present, there is no literature on the outcomes of robotic-assisted laparoscopic pyeloplasty (RALPyelo) in a Canadian context. Our objective was to perform a retrospective review of RALPyelo cases at a high-volume Canadian center. METHODS: We performed a retrospective review of patients who underwent RALPyelo at St. Michael's Hospital, between January 2012 and May 2019. Demographics, operative details, and pre- and postoperative imaging results (ultrasounds, computed tomography [CT] scans, and diuretic renal scan [DRS ]) were recorded. Patients were excluded if at least one-year followup data was unavailable. Our primary outcome was clinical and radiologic improvement defined as 1) symptom improvement; 2) stable/improved split renal function on DRS ; and 3) either improvement in the degree of hydronephrosis on ultrasound or CT, or improved drainage time on DRS. Secondary outcomes included postoperative complications, need for diagnostic intervention, and reintervention for recurrent UPJO. RESULTS: A total of 156 patients underwent RALPyelo after exclusions. The median age was 42 and 66% were female. Mean followup was 2.5 years. For our primary outcome, 87% had clinical and radiologic improvement. Diagnostic investigation for possible recurrent/persistent obstruction, based on symptoms and/or imaging results, was required in 17% of cases, but only 3% required reintervention for recurrent UPJO. Accordingly, the overall treatment success was 97%. The most common postoperative complication was urinary tract infection (18%), and urine leak was seen in only 2% of patients. CONCLUSIONS: The results of our study compare favorably with currently reported outcomes in the literature and demonstrate the safety and high level of success of RALPyelo at a high-volume Canadian center.

6.
J Urol ; 189(6): 2112-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23276509

ABSTRACT

PURPOSE: Controversy exists regarding antibiotic prophylaxis before shock wave lithotripsy. The AUA (American Urological Association) guideline recommends universal antibiotic prophylaxis, whereas the EAU (European Association of Urology) guideline recommends prophylaxis only for select patients. We evaluated the use of targeted antibiotic prophylaxis in preventing urinary tract infections in patients undergoing shock wave lithotripsy. MATERIALS AND METHODS: A prospective single cohort study was performed during 6 months with patients undergoing shock wave lithotripsy. All patients underwent urine dipstick and culture before shock wave lithotripsy. Targeted antibiotic prophylaxis was provided at the discretion of the treating urologist. All patients had a urine culture performed after shock wave lithotripsy and completed a survey documenting fevers or urinary symptoms. The primary outcome was the incidence of urinary tract infections, urosepsis and asymptomatic bacteriuria after shock wave lithotripsy. The secondary outcome was the sensitivity and specificity of urinary dipstick leukocytes and nitrites. RESULTS: A total of 526 patients were enrolled in the study. Of the 389 patients included in the determination of the primary outcome, urinary tract infection developed in only 1 (0.3%), urosepsis did not develop in any patients and asymptomatic bacteriuria developed in 11 (2.8%). Eight (2.1%) patients were administered antibiotic prophylaxis. The specificity of urine dipstick nitrites was high (95%) while the sensitivity was poor (9.7%). CONCLUSIONS: In our cohort study using targeted antibiotic prophylaxis the rates of urinary tract infection after shock wave lithotripsy and rates of asymptomatic bacteriuria were extremely low, with no development of urosepsis. This finding questions the need for universal antibiotic prophylaxis before shock wave lithotripsy.


Subject(s)
Antibiotic Prophylaxis/methods , Bacteriuria/epidemiology , Lithotripsy/adverse effects , Urinary Tract Infections/epidemiology , Urolithiasis/therapy , Adult , Age Distribution , Bacteriuria/etiology , Bacteriuria/prevention & control , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Kidney Calculi/diagnosis , Kidney Calculi/therapy , Lithotripsy/methods , Male , Middle Aged , Prospective Studies , Risk Assessment , Severity of Illness Index , Sex Distribution , Ureteral Calculi/diagnosis , Ureteral Calculi/therapy , Urinalysis , Urinary Tract Infections/etiology , Urinary Tract Infections/prevention & control , Urolithiasis/diagnosis
7.
Cent European J Urol ; 76(1): 57-63, 2023.
Article in English | MEDLINE | ID: mdl-37064265

ABSTRACT

Introduction: Ureteral double-J stent length is an important factor affecting stent-related symptoms. Multiple techniques exist to determine ideal stent length for a given patient, however, little is known about what techniques urologists rely on. Our objective was to identify how urologists determine optimal stent length. Material and methods: An online survey was e-mailed in 2019 to all members of the Endourology Society. The survey sought to assess what methods are commonly used to determine choice of stent length, along with frequency of stent placement post ureteroscopy, duration of stenting, availability of different stent lengths and the use of stent tether. Results: 301 urologists (15.1%) responded to our survey. Following ureteroscopy, 84.5% of respondents would stent at least 50% of the time. Following uncomplicated ureteroscopy, most respondents (52.0%) would leave a stent for 2-7 days. Patient height was most commonly ranked first as the method of choice in determining stent length (47.0%), followed by estimation based on experience only (20.6%) and intra-operative direct measurement of ureteric length (19.1%). Most respondents utilized multiple methods in determination of optimal stent length. Most respondents (66.5%) were interested in a simple intra-operative technique utilizing a special ureteral catheter that would help choose the most appropriate stent length. Conclusions: Post-ureteroscopy stent insertion is common and patient height is the most common method of choice used in determining optimal stent length. Most respondents were interested in using a simple, novel ureteral catheter device that would allow them to more accurately select optimal stent length.

8.
Tumour Biol ; 33(1): 131-40, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22086373

ABSTRACT

Metastasis results in most of the cancer deaths in clear cell renal cell carcinoma (ccRCC). MicroRNAs (miRNAs) regulate many important cell functions and play important roles in tumor development, metastasis and progression. In our previous study, we identified a miRNA signature for metastatic RCC. In this study, we validated the top differentially expressed miRNAs on matched primary and metastatic ccRCC pairs by quantitative polymerase chain reaction. We performed bioinformatics analyses including target prediction and combinatorial analysis of previously reported miRNAs involved in tumour progression and metastasis. We also examined the co-expression of the miRNAs clusters and compared expression of intronic miRNAs and their host genes. We observed significant dysregulation between primary and metastatic tumours from the same patient. This indicates that, at least in part, the metastatic signature develops gradually during tumour progression. We identified metastasis-dysregulated miRNAs that can target a number of genes previously found to be involved in metastasis of kidney cancer as well as other malignancies. In addition, we found a negative correlation of expression of miR-126 and its target vascular endothelial growth factor (VEGF)-A. Cluster analysis showed that members of the same miRNA cluster follow the same expression pattern, suggesting the presence of a locus control regulation. We also observed a positive correlation of expression between intronic miRNAs and their host genes, thus revealing another potential control mechanism for miRNAs. Many of the significantly dysregulated miRNAs in metastatic ccRCC are highly conserved among species. Our analysis suggests that miRNAs are involved in ccRCC metastasis and may represent potential biomarkers.


Subject(s)
Biomarkers, Tumor/physiology , Carcinoma, Renal Cell/secondary , Kidney Neoplasms/pathology , MicroRNAs/physiology , Biomarkers, Tumor/genetics , Computational Biology , Humans , Male , MicroRNAs/genetics , Neoplasm Metastasis , Oligonucleotide Array Sequence Analysis , Vascular Endothelial Growth Factor A/genetics
9.
J Urol ; 186(2): 556-62, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21684557

ABSTRACT

PURPOSE: Although shock wave lithotripsy is dependent on patient and stone related factors, there are few reliable algorithms predictive of its success. In this study we develop a comprehensive nomogram to predict renal and ureteral stone shock wave lithotripsy outcomes. MATERIALS AND METHODS: During a 5-year period data from patients treated at our lithotripsy unit were reviewed. Analysis was restricted to patients with a solitary renal or ureteral calculus 20 mm or less. Demographic, stone, patient, treatment and 3-month followup data were collected from a prospective database. All patients were treated using the Philips LithotronĀ® lithotripter. RESULTS: A total of 422 patients (69.7% male) were analyzed. Mean stone size was 52.3Ā±39.3 mm2 for ureteral stones and 78.9Ā±77.3 mm2 for renal stones, with 95 (43.6%) of the renal stones located in the lower pole. The single treatment success rates for ureteral and renal stones were 60.3% and 70.2%, respectively. On univariate analysis predictors of shock wave lithotripsy success, regardless of stone location, were age (p=0.01), body mass index (p=0.01), stone size (p<0.01), mean stone density (p<0.01) and skin to stone distance (p<0.01). By multivariate logistic regression for renal calculi, age, stone area and skin to stone distance were significant predictors with an AUC of 0.75. For ureteral calculi predictive factors included body mass index and stone size (AUC 0.70). CONCLUSIONS: Patient and stone parameters have been identified to create a nomogram that predicts shock wave lithotripsy outcomes using the Lithotron lithotripter, which can facilitate optimal treatment based decisions and provide patients with more accurate single treatment success rates for shock wave lithotripsy tailored to patient specific situations.


Subject(s)
Kidney Calculi/therapy , Lithotripsy , Nomograms , Ureteral Calculi/therapy , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Remission Induction
10.
J Urol ; 186(3): 1077-83, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21784468

ABSTRACT

PURPOSE: Renal cell carcinoma is the most common neoplasm of the adult kidney. Currently to our knowledge there are no biomarkers for diagnostic, prognostic or predictive applications for renal cell carcinoma. miRNAs are nonprotein coding RNAs that negatively regulate gene expression and are potential biomarkers for cancer. MATERIALS AND METHODS: We analyzed 70 matched pairs of clear cell renal cell carcinoma and normal kidney tissues from the same patients by microarray analysis and validated our results by quantitative real-time polymerase chain reaction. We also performed extensive bioinformatic analysis to explore the role and regulation of miRNAs in clear cell renal cell carcinoma. RESULTS: We identified 166 miRNAs that were significantly dysregulated in clear cell renal cell carcinoma, including miR-122, miR-155 and miR-210, which had the highest over expression, and miR-200c, miR-335 and miR-218, which were most down-regulated. Analysis of previously reported miRNAs dysregulated in RCC showed overall agreement in the direction of dysregulation. Extensive target prediction analysis revealed that many miRNAs were predicted to target genes involved in renal cell carcinoma pathogenesis. In renal cell carcinoma miRNA dysregulation can be attributed in part to chromosomal aberrations, co-regulation of miRNA clusters and co-expression with host genes. We also performed a preliminary analysis showing that miR-155 expression correlated with clear cell renal cell carcinoma size. This finding must be validated in a larger independent cohort. CONCLUSIONS: Analysis showed that miRNAs are dysregulated in clear cell renal cell carcinoma and may contribute to kidney cancer pathogenesis by targeting more than 1 key molecule. We identified mechanisms that may contribute to miRNA dysregulation in clear cell renal cell carcinoma. Dysregulated miRNAs represent potential biomarkers for kidney cancer.


Subject(s)
Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , MicroRNAs/genetics , Genetic Markers/genetics , Humans
11.
BJU Int ; 107(4): 636-41, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20804483

ABSTRACT

OBJECTIVES: To objectively quantify the recovery of health-related quality of life (HRQL) in patients undergoing laparoscopic nephrectomy. To determine which factors are predictive of a more expedited recovery. MATERIALS AND METHODS: Patient recovery was prospectively measured among patients undergoing laparoscopic simple (n= 12), radical (n= 42) and donor (n= 95) nephrectomy. All procedures were performed using a 3- or 4-trocar, transperitoneal fully-laparoscopic technique with intact specimen extraction using impermeable sacs for simple and radical nephrectomy, and hand extraction for donor nephrectomy. Postoperative recovery and quality of life were measured using the Postoperative Recovery Scale (PRS) administered preoperatively, immediately postoperatively and as an outpatient at 4, 8, 12, and 16 weeks postoperatively. ANOVA and Pearson's χĀ² tests were performed on demographic data. Multivariate logistic regression analysis was used to calculate odds ratios for factors predictive of recovery. RESULTS: Statistically significant differences were found at baseline for age (P = 0.02), gender (P < 0.01), body mass index (BMI; P = 0.03), surgical side (P < 0.01) and activity-based lifestyle (P = 0.04) across the three groups. Minimal adverse events were seen. Factors predictive of expedited recovery include age < 50 years (OR: 2.1, P < 0.01), body-mass index (BMI) < 30 kg/mĀ² (OR: 1.7, P < 0.01), active lifestyles (OR: 1.3, P < 0.01) and those patients undergoing nephrectomy for benign or malignant indications rather than for organ donation (OR: 1.4, P < 0.01). There was a significant delay in the donor group vs the non-donor group with respect to the median number of days both groups took to recover 75% and 90% of their baseline PRS scores (11 days, P = 0.02; 20 days, P = 0.02, respectively). CONCLUSIONS: Predictive factors of recovery from laparoscopic nephrectomy include age, BMI, lifestyle and surgical indication. Differences between HRQL recovery following donor vs non-donor laparoscopic nephrectomy are significant, and suggest the possible interplay of underlying psychological factors.


Subject(s)
Kidney Diseases/rehabilitation , Laparoscopy , Nephrectomy/rehabilitation , Quality of Life , Adult , Epidemiologic Methods , Female , Humans , Kidney Diseases/surgery , Kidney Transplantation , Living Donors , Male , Middle Aged , Nephrectomy/methods , Treatment Outcome
12.
Urology ; 147: 150-154, 2021 01.
Article in English | MEDLINE | ID: mdl-33166541

ABSTRACT

OBJECTIVE: To review our experience using clips to control the renal vessels during laparoscopic donor nephrectomy (LDN) and determine the safety of this practice. METHODS: We performed a retrospective review of patients who underwent LDN at our centre January 1, 2007-September 17, 2019. The primary outcome was the rate of complication associated with vascular control of the renal vessels, which included (1) conversion to open to manage bleeding, (2) additional procedures for bleeding, and (3) major bleeding requiring blood transfusion. Secondary outcomes included the rate of renal artery/vein clip dislodgement or crossing, change in hemoglobin, warm ischemia time and the incidence of intra-operative complications and postoperative in-hospital complications. RESULTS: We included 503 patients who underwent LDN, of which 497 were left sided. The main renal artery was controlled with 3 titanium clips in 489 (97%) cases. The main renal vein was controlled with 2 polymer-locking clips in 478 (95%) cases. For our primary outcome, there were no conversions to open to manage bleeding, no secondary procedures due to bleeding and no major bleeding requiring blood transfusion. Additionally, there were no donor deaths. Regarding our secondary outcomes, there were 5 intraoperative events related to the titanium clips being placed on the renal artery and 1 intraoperative event related to the polymer-locking clips on the renal vein, none of which resulted in any morbidity. CONCLUSION: Using 3 titanium clips on the renal artery and 2 polymer-locking clips on the renal vein during left LDN is safe and provides excellent vascular control.


Subject(s)
Blood Loss, Surgical/prevention & control , Hemostasis, Surgical/instrumentation , Laparoscopy/adverse effects , Nephrectomy/adverse effects , Postoperative Complications/epidemiology , Tissue and Organ Harvesting/adverse effects , Adult , Blood Loss, Surgical/statistics & numerical data , Feasibility Studies , Female , Hemostasis, Surgical/methods , Humans , Incidence , Kidney/blood supply , Kidney/surgery , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Laparoscopy/instrumentation , Living Donors , Male , Middle Aged , Nephrectomy/instrumentation , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Renal Artery/surgery , Renal Veins/surgery , Retrospective Studies , Tissue and Organ Harvesting/instrumentation , Transplant Donor Site/blood supply , Transplant Donor Site/surgery , Warm Ischemia/statistics & numerical data
13.
Biol Chem ; 391(4): 411-23, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20180642

ABSTRACT

Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and currently no diagnostic marker exists. Kallikrein-related peptidases (KLKs) have been implicated in numerous cancers including ovarian, prostate, and breast carcinoma. KLKs 5, 6, 10, and 11 have decreased expression in RCC when compared to normal kidney tissue. Our bioinformatic analysis indicated that the KLK 1, 6, and 7 genes have decreased expression in RCC. We experimentally verified these results and found that decreased expression of KLKs 1 and 3 were significantly associated with the clear cell RCC subtype (p<0.001). An analysis of miRNAs differentially expressed in RCC showed that 61 of the 117 miRNAs that were reported to be dysregulated in RCC were predicted to target KLKs. We experimentally validated two targets using two independent approaches. Transfection of miR-224 into HEK-293 cells resulted in decreased KLK1 protein levels. A luciferase assay demonstrated that hsa-let-7f can target KLK10 in the RCC cell line ACHN. Our results, showing differential expression of KLKs in RCC, suggest that KLKs could be novel diagnostic markers for RCC and that their dysregulation could be under miRNA control. The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications.


Subject(s)
Carcinoma, Renal Cell/metabolism , Kallikreins/metabolism , Kidney Neoplasms/metabolism , MicroRNAs/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/enzymology , Carcinoma, Renal Cell/genetics , Chromosome Aberrations , Computational Biology , Evolution, Molecular , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/enzymology , Kidney Neoplasms/genetics , MicroRNAs/genetics , Phylogeny , Reproducibility of Results
14.
J Urol ; 183(2): 743-51, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20022054

ABSTRACT

PURPOSE: miRNAs are small, nonprotein coding RNAs that are differentially expressed in many malignancies. We previously identified 80 miRNAs that are dysregulated in clear cell renal cell carcinoma. In this study we validated over expression of the miR-17-92 cluster in clear cell renal cell carcinoma and tested the effect of 2 members of this cluster (miR-17-5p and miR-20a) on tumor proliferation. We also elucidated the role of miRNA in clear cell renal cell carcinoma pathogenesis with bioinformatics. MATERIALS AND METHODS: miRNA expression was validated by quantitative reverse transcriptase-polymerase chain reaction. The cell proliferation effect of miR-17-5p and miR-20a was tested in a renal adenocarcinoma cell line model. Multiple in silico analyses were done of dysregulated miRNAs. RESULTS: We validated miR-71-92 cluster over expression in clear cell renal cell carcinoma by quantitative reverse transcriptase-polymerase chain reaction. Transfection of miR-20a inhibitor significantly decreased cell proliferation in a dose dependent manner. Transfection of miR-17-5p, which is not endogenously expressed in the ACHN cell line, led to increased cell proliferation compared to control values. This effect was suppressed by miR-17-5p inhibitor. Bioinformatics analysis identified 10 clusters of miRNAs dysregulated in clear cell renal cell carcinoma that followed the same expression patterns. We also identified matching patterns between reported chromosomal aberration in clear cell renal cell carcinoma and miRNA dysregulation for 37.5% of the miRNAs. Target prediction analysis was done using multiple algorithms. Many key molecules in clear cell renal cell carcinoma pathogenesis, including HIFs, mTOR, VEGF and VHL, were potential targets for dysregulated miRNAs. CONCLUSIONS: A significant number of dysregulated proteins in clear cell renal cell carcinoma are potential miRNA targets. Also, many clear cell renal cell carcinoma dysregulated miRNAs are phylogenetically conserved.


Subject(s)
Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , MicroRNAs/genetics , Humans
15.
Urol Res ; 38(4): 307-13, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20625891

ABSTRACT

Shock wave lithotripsy (SWL) is considered the first line treatment for the majority of patients with renal and ureteric calculi, with success rates from contemporary series varying from 60 to 90%. Success is dependent on many patient and stone-related factors. We conducted a retrospective analysis of mean stone CT density (MSD) and skin-to-stone distance (SSD) to determine their influence on the success of SWL of renal and ureteric calculi. Data from all patients treated at the St. Michael's Hospital Lithotripsy Unit from May 2004 to June 2009 were reviewed. Analysis was restricted to those patients with a pre-treatment non-contrast CT scan conducted at our center demonstrating a solitary renal or ureteric calculus < or =20 mm in maximal diameter. Successful treatment of renal stones was defined as those patients who were stone free or had asymptomatic, clinically insignificant residual fragments < or =4 mm in diameter, as measured by KUB X-ray, 3 months after a single SWL treatment. Successful treatment of ureteric stones was defined as being stone free on KUB X-ray, 2-weeks post-SWL. Demographic, stone, patient, treatment and follow-up data were collected from a prospective database and review of CT and KUB imaging by two independent urologists and one radiologist. Data were analyzed with logistic regression, Chi square analysis and ANOVA where appropriate. 422 patients (69.7% male) with a mean age of 51.4 years (SD 12.9) and mean BMI 27.0 kg/m(2) (SD 4.9) were analyzed. Mean stone size was 78.9 mm(2) (SD 77.3) for ureteral stones and 66.1 mm(2) (SD 63.2) for renal stones, with 95 (43.6%) of the renal stones located in the lower pole. The single-treatment success rates for ureteral and renal stones were 62.3% and 68.8%, respectively. On univariate analysis, predictors of SWL success, regardless of stone location, were age (p = 0.01), BMI (p = 0.01), stone size (p < 0.01), MSD (p < 0.01) and SSD (p < 0.01). On multivariate analysis, MSD >900 HU (OR = 0.49, CI: 0.32-0.75) and SSD >110 mm (OR = 0.49, CI: 0.31-0.78) were both significant predictors of outcome. We have identified in a large series of renal and ureteric calculi that both MSD and SSD can reliably predict SWL outcomes. This data can be used in combination with other patient and stone-related factors to facilitate optimal treatment-based decisions and provide patients with more accurate single-treatment success rates for SWL.


Subject(s)
Kidney Calculi/therapy , Lithotripsy/standards , Ureteral Calculi/therapy , Female , Humans , Kidney Calculi/diagnostic imaging , Lithotripsy/methods , Male , Middle Aged , Multivariate Analysis , Particle Size , Predictive Value of Tests , Tomography, X-Ray Computed , Ureteral Calculi/diagnostic imaging
16.
Prog Transplant ; 30(4): 360-364, 2020 12.
Article in English | MEDLINE | ID: mdl-32964779

ABSTRACT

INTRODUCTION: Routine crossmatch of packed red blood cells (pRBCs) is completed preoperatively at many centers despite conflicting evidence on the incidence of blood transfusions with renal transplantation. In the current economic climate, resource adjudication should be judicious and medically appropriate. The objective of this study was to determine the incidence, timing, and predictors of early postoperative pRBC transfusion in patients undergoing renal transplantation. METHODS: A retrospective review of all patients undergoing renal transplantation at our institution from January 2013 to May 2016 was performed. Demographic, biochemical, and clinical parameters were recorded. The primary outcome was early postoperative transfusion, defined as an intraoperative transfusion or within 2 days of surgery. Multivariable logistic regression was performed to identify associations with early postoperative transfusion. RESULTS: We identified 428 patients during the study period (average age 55 years, 60% male, 30% obese, 67% deceased donor, and 43% preoperative antithrombotic use). Forty (9.3%) patients required early postoperative transfusion (mean: 2.8 pRBCs/transfusion) and most did not require blood urgently. Only 20 (4.7%) patients required a transfusion intraoperatively or on the same day of surgery. Lower preoperative hemoglobin (per g/L unit: odds ratio [OR]: 0.943), female gender (OR: 2.752), and preoperative antithrombotic use (OR 2.369) were associated with a need for early postoperative transfusion. CONCLUSION: Transfusion in the early postoperative period following renal transplantation was less than 10%, suggesting that routine crossmatch may not be necessary for all patients. Preoperative hemoglobin, female gender, and preoperative antithrombotic use were associated with increased risk and may be useful to risk-stratify patients who require crossmatch.


Subject(s)
Blood Grouping and Crossmatching/standards , Blood Transfusion/standards , Kidney Transplantation/standards , Postoperative Care/standards , Postoperative Hemorrhage/therapy , Practice Guidelines as Topic , Adult , Aged , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Ontario , Retrospective Studies
17.
Urology ; 143: 80-84, 2020 09.
Article in English | MEDLINE | ID: mdl-32473206

ABSTRACT

OBJECTIVE: To determine how effective routine postoperative blood work is in identifying complications after percutaneous nephrolithotomy (PCNL), the gold standard treatment for large volume stone disease. Although major complication rates are low, hemorrhagic and sepsis-related complications are serious and can occur. Routine post-PCNL complete blood count is routinely performed by most endourologists but may be a low-value practice. METHODS: A retrospective review was performed of all PCNL procedures at our center over a 3-year period. Patient demographic, stone characteristics and postoperative data were collected and analyzed. RESULTS: Three hundred and eighty-five patients (196 female and 189 males) underwent PCNL for the treatment of urolithiasis. Mean age was 55.8 years and mean length of stay in hospital was 1.74 days. Most patients (82.9%) had neither ureteric stent nor percutaneous tube prior to PCNL. Postoperatively, 4 patients (1.0%) required a blood transfusion and 14 patients (3.6%) developed urosepsis. Patients who required either a transfusion or developed urosepsis demonstrated abnormal vital signs (tachycardia, hypotension, or fever) postoperatively. Sixteen patients (4.2%) had normal vital signs but had an extended hospital stay only to monitor abnormal blood work results. None these patients required a transfusion nor developed urosepsis but had a length of stay that was a mean of 1.5 days longer patients with normal postoperative vital signs and blood work. CONCLUSION: Abnormal vital signs alone identified all patients that required transfusion or treatment for urosepsis after PCNL. Routine complete blood count testing postoperatively may not improve detection of infectious or bleeding complications and may prolong hospital admission unnecessarily.


Subject(s)
Hematologic Tests , Kidney Calculi , Nephrolithotomy, Percutaneous , Postoperative Complications , Postoperative Hemorrhage , Sepsis , Blood Transfusion/statistics & numerical data , Canada/epidemiology , Female , Hematologic Tests/methods , Hematologic Tests/statistics & numerical data , Humans , Kidney Calculi/epidemiology , Kidney Calculi/pathology , Kidney Calculi/surgery , Length of Stay/statistics & numerical data , Low-Value Care , Male , Medical Overuse/prevention & control , Middle Aged , Nephrolithotomy, Percutaneous/adverse effects , Nephrolithotomy, Percutaneous/methods , Nephrolithotomy, Percutaneous/statistics & numerical data , Outcome Assessment, Health Care , Postoperative Complications/blood , Postoperative Complications/diagnosis , Postoperative Hemorrhage/blood , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/therapy , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/trends , Retrospective Studies , Sepsis/blood , Sepsis/etiology , Sepsis/therapy , Severity of Illness Index
18.
Can Urol Assoc J ; 14(2): 12-16, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31364975

ABSTRACT

INTRODUCTION: Following the introduction of shock wave lithotripsy (SWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL), the subspecialty of endourology was born in the late 1970s. The purpose of this study was to report milestones in Canadian endourology, highlighting Canada's contributions to the field. METHODS: A review of the literature was performed from the late 1970s to the present. The literature review included bibliographic and digital resources. Additionally, records and recollections by various individuals were used, including some who were directly involved. RESULTS: Endourology was born in Canada when SWL, URS, and PCNL emerged as minimally invasive treatment options for stones in the early to mid-1980s. According to our research, the first PCNL was performed at the University of Toronto in 1981. Dr. Joachim Burhenne, a Harvard-trained radiologist from Germany, first used extracorporeal SWL in Canada at the University of British Columbia (UBC) for the treatment of biliary stones. Treatment for urinary tract stones followed at UBC and Dalhousie University. The first worldwide use of the holmium laser for lithotripsy of urinary tract calculi took place at the University of Western Ontario. Other endourology milestones in Canada include the formation of the Canadian Endourology Group and the emergence of the Endourological Society-accredited fellowship programs at the University of Toronto and Western University in the 1990s. Canada hosted the 21st and 35th World Congress of Endourology and Shock Wave Lithotripsy annual meeting in Montreal and Vancouver, respectively. CONCLUSIONS: Canadian urologists have led many advances in SWL, URS, and PCNL over the past four decades and, for a relatively small community, have made significant contributions to the field. Through the training of the next generation of endourologists at Canadian institutions, the future of endourology in Canada is bright.

19.
J Nutr ; 139(4): 743-9, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19211830

ABSTRACT

Poor eating habits, a strong predictor of health outcomes, are not objectively assessed in routine clinical practice. In this study, we evaluated the use of urinary potassium (K(+)) as a means to identify people consuming a poor quality diet. Consecutive patients with kidney stones (n = 220), aged 18-50 y, from a population-based lithotripsy unit, collected a single 24-h urine sample to assess urinary K(+). They also completed a FFQ to derive the recommended foods score (RFS), an index of overall diet quality, and had their blood pressure, heart rate, weight, and height measured. Urinary K(+) was related positively with the intake of recommended food items, including vegetables, fruit, whole grains, low-fat dairy products, fish and poultry, and wine and negatively to those not recommended by current dietary guidelines, including red meat, fast food, and high-energy drinks. Urinary K(+) was also correlated with the RFS (r = 0.226; P < 0.001). Using a receiver operating characteristic curve, K(+) excretion values below the gender-specific median (men, 60 mmol/d; women, 41 mmol/d) were identified as the optimal cutoff values for a poor quality diet, indicated by the RFS. Higher urinary K(+) was inversely related to adjusted BMI (P-trend = 0.03), diastolic blood pressure (P-trend = 0.04) and heart rate (P-trend = 0.006), after controlling for potential confounders. Urinary K(+) provides a summary measure of diet quality, is significantly related to BMI, blood pressure, and heart rate, and may be useful clinically to detect poor dietary habits and monitor response to dietary interventions.


Subject(s)
Diet/statistics & numerical data , Potassium/urine , Adolescent , Adult , Female , Health , Humans , Male , Middle Aged
20.
J Endourol ; 33(4): 314-318, 2019 04.
Article in English | MEDLINE | ID: mdl-30724110

ABSTRACT

INTRODUCTION: Routine preoperative electrocardiogram (ECG) before shockwave lithotripsy (SWL) is frequently performed despite recommendations against its use in asymptomatic patients undergoing low-risk surgical procedures. This study assesses whether routine preoperative ECG before SWL is useful in patients at low risk for cardiac complications. MATERIALS AND METHODS: A retrospective study of SWL at our center (2003-2013) reviewed all cardiac-related preoperative cancellations, intraoperative complications, postoperative admissions, and emergency department presentations in patients at low risk for cardiac complications. Patients received SWL with sedation and continuous five-lead ECG monitoring. RESULTS: Of 30,892 referrals, preoperative ECG triggered 13 (0.04%) cancelations in low-risk patients (1 with new atrial fibrillation and 12 with ischemia/previous infarction). Of these patients, 1 had a subsequent abnormal cardiac work-up and 11 underwent uncomplicated SWL without cardiac intervention (2 had unknown history). Of 27,722 treatments, 5 (0.02%) were stopped prematurely in low-risk patients because of arrhythmia (3 had normal preoperative ECG, 1 had abnormal ECG, and 1 did not complete ECG). Three patients developed an arrhythmia with sedation and 2 patients were admitted postoperatively because of cardiac complications (1 for atrial fibrillation and 1 for hypertension), of whom all had normal preoperative ECG. No patients presented to our emergency department with cardiac complications after SWL. CONCLUSIONS: In patients at low risk for cardiac complications, preoperative ECG triggered very few cancellations and did not predict early termination of treatment or cardiac complications after SWL. These findings suggest that in low-risk patients, routine preoperative ECG has little effect on treatment or complication rate and should be omitted.


Subject(s)
Atrial Fibrillation/diagnostic imaging , Electrocardiography , Intraoperative Complications/etiology , Lithotripsy/methods , Female , Hospitalization , Humans , Male , Middle Aged , Postoperative Complications , Preoperative Period , Retrospective Studies , Risk , Urolithiasis
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