Is extracorporeal shockwave lithotripsy a risk factor for the development of diabetes mellitus? A population-based study.

OBJECTIVE: To determine if patients treated with extracorporeal shockwave lithotripsy (ESWL) are at a greater risk of developing diabetes mellitus (DM) than those treated with ureteroscopy (URS). PATIENTS AND METHODS: A retrospective population-based cohort study was performed of all ESWL and URS stone treatments done in Ontario between January 1994 and March 2014, utilising linked encoded healthcare databases. The primary outcome was the development of DM >90 days after treatment. The Kaplan-Meier method was used for unadjusted survival analysis and multivariable analysis with Cox proportional hazards regression was used to assess the risk of DM between the ESWL and URS groups whilst controlling for age, gender, region of residence, income quintile, year of treatment, and comorbidity index. A sensitivity analysis with a subset of ESWL patients treated for left renal or proximal ureteric stones was completed. RESULTS: We identified 106 963 patients who underwent ESWL or URS over the study period with a median follow-up of 6.6 years (ESWL 8.5 years, URS 5.6 years). Unadjusted survival analysis showed an increased risk of developing DM in the ESWL group compared to the URS group (P < 0.001); however, multivariable analysis showed no increased risk of DM in the ESWL cohort (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.91-1.02; P = 0.25). Similarly, sensitivity analysis showed no increased risk of DM in the left renal/proximal ureteric stone ESWL cohort compared to the URS cohort (HR 1.04, 95% CI 0.96-1.13; P = 0.35). CONCLUSIONS: Our population-based cohort study demonstrated no increased risk of DM in patients undergoing ESWL compared to URS.

Basic Laparoscopic Skills Assessment Study: Validation and Standard Setting among Canadian Urology Trainees.

PURPOSE: As urology training programs move to a competency based medical education model, iterative assessments with objective standards will be required. To develop a valid set of technical skills standards we initiated a national skills assessment study focusing initially on laparoscopic skills. MATERIALS AND METHODS: Between February 2014 and March 2016 the basic laparoscopic skill of Canadian urology trainees and attending urologists was assessed using 4 standardized tasks from the AUA (American Urological Association) BLUS (Basic Laparoscopic Urological Surgery) curriculum, including peg transfer, pattern cutting, suturing and knot tying, and vascular clip applying. All performances were video recorded and assessed using 3 methods, including time and error based scoring, expert global rating scores and C-SATS (Crowd-Sourced Assessments of Technical Skill Global Rating Scale), a novel, crowd sourced assessment platform. Different methods of standard setting were used to develop pass-fail cut points. RESULTS: Six attending urologists and 99 trainees completed testing. Reported laparoscopic experience and training level correlated with performance (p <0.01). Attending urologists were significantly better than trainees (p <0.05), demonstrating construct validity evidence for the 4 AUA BLUS tasks. The C-SATS method of assessment correlated well with the traditional methods of time and error based scoring, and the global rating scale. We were able to use relative and absolute standard setting methods to define pass-fail cut points for all 4 AUA BLUS tasks. CONCLUSIONS: The 4 AUA BLUS tasks demonstrated good construct validity evidence for use in assessing basic laparoscopic skill. Performance scores using the novel C-SATS platform correlated well with traditional time-consuming methods of assessment. Various standard setting methods were used to develop pass-fail cut points for educators to use when making formative and summative assessments of basic laparoscopic skill.

Same Session Bilateral Ureteroscopy for Multiple Stones: Results from the CROES URS Global Study.

PURPOSE: This study presents a comparison of the international experience with ipsilateral and bilateral ureteroscopy for multiple, bilateral ureteral and renal stones vs single stone treatment. Patient and treatment characteristics and outcomes were compared. MATERIALS AND METHODS: The CROES (Clinical Research Office of the Endourological Society) Ureteroscopy Global Study includes 114 centers in 32 countries. Patients undergoing bilateral ureteroscopy, ipsilateral ureteroscopy for multiple stones and ureteroscopy for a single stone were examined from January 2010 to October 2012. Intraoperative characteristics and postoperative outcomes were identified for each patient. Inverse probability weighted regression adjustment analyses were done to compare outcomes independent of differences among centers and patient characteristics. RESULTS: The CROES Ureteroscopy Global Study consists of 11,885 patients. A total of 2,153 patients (18.7%) were treated for multiple stones, of whom 1,880 (87.3%) and 273 (12.7%) underwent ipsilateral and bilateral ureteroscopy, respectively. Inverse probability weighted regression adjustment models for bilateral vs ipsilateral ureteroscopy and multiple vs single stone treatments showed that patients with bilateral ureteroscopy and multiple stone treatments had lower stone-free rates, higher re-treatment rates and longer operative times compared to patients who underwent ipsilateral ureteroscopy and single stone treatment. There was no difference in complication rates among bilateral, ipsilateral and single stone ureteroscopy. CONCLUSIONS: This study presents a large series of patients who underwent bilateral and ipsilateral ureteroscopy. Our findings suggest a decrease in stone-free rates, increased re-treatment rates, increased operative times and longer hospital stay in patients treated for multiple stones. The treatment of multiple stones and bilateral ureteroscopy are safe compared to single stone treatment and ipsilateral ureteroscopy, respectively.

Shockwave lithotripsy: techniques for improving outcomes.

OBJECTIVES: Shock wave lithotripsy (SWL) remains the only effective truly non-invasive treatment for nephrolithiasis. While single-treatment success rates may not equal those of ureteroscopy and percutaneous nephrolithotomy, it has an important role to play in the management of stones. In this paper, we outline the latest evidence-based recommendations for maximizing SWL outcomes, while minimizing complications. MATERIALS AND METHODS: A comprehensive review of the current literature was performed regarding maximizing SWL outcomes. RESULTS: Several different considerations need to be made regarding patient selection with respect to body habitus, body mass index, anatomical location and underlying urologic abnormalities. Stone composition and stone density (Hounsfield Units) are important prognostic variables. Patient positioning is critical to allow for adequate stone localization with either fluoroscopy or ultrasound. Coupling should be optimized with a low viscosity gel applied to the therapy head first and patient movement should be limited. SWL energy should be increased slowly and shockwave rates of 60 or 90 Hz should be used. Medical expulsive therapy with alpha-blockers after SWL treatment has shown benefit, particularly with stones greater than 10 mm. CONCLUSION: While single-treatment success rates may not equal those of ureteroscopy or percutaneous nephrolithotomy, with proper patient selection, optimization of SWL technique, and use of adjunctive treatment after SWL, success rates can be maximized while further reducing the already low rate of serious complications. SWL remains an excellent treatment option for calculi even in 2017.

Stone technology: intracorporeal lithotripters.

PURPOSE: Intracorporeal lithotripsy is becoming the most commonly used surgical method of stone treatment in Urology. The five major types of intracorporeal lithotripters are ultrasonic, ballistic, and combination lithotripters as well as laser and electrohydraulic lithotripters. The advantages and disadvantages of choosing each of these treatment modalities are reviewed. METHODS: Extensive review of literature was performed to identify the types of intracorporeal lithotripters. An investigation was undertaken of the early development of each modality of intracorporeal lithotripsy and/or the mechanism of action. Challenges of each technique were identified and presented. Finally, a determination was made of how these lithotripters compare on the basis of effectiveness of action and cost based on information provided in primary literature as well as previous reviews of these modalities. RESULTS: Contemporary lithotripters have found widespread use in the management of urinary lithiasis. Holmium laser lithotripsy has become one of the most commonly used tools for intracorporeal lithotripsy. CONCLUSION: There is a wide variety of intracorporeal lithotripters which can be chosen based on the characteristics of each modality and the requirements of the urologist.

Medical Expulsive Therapy: Worthwhile or Wishful Thinking.

PURPOSE OF REVIEW: We set out to provide an overview of the most recent evidence for medical expulsive therapy (MET). Conflicting level 1 evidence for and against the use of MET has been published. RECENT FINDINGS: The largest double-blind randomized control trial (1110 patients) comparing placebo, tamsulosin, and nifedipine found no benefit for MET in preventing the need for secondary intervention. A recent meta-analysis of 55 randomized trials using alpha-blockers suggests that no benefit is seen with smaller ureteric calculi, but patients with larger ureteric calculi experience shorter times to stone passage, fewer episodes of pain, require less surgical intervention, and fewer hospital admissions. All the major urological organizations (American Urological Association, European Association of Urology, Canadian Urological Association) suggest offering MET as part of conservative management for appropriate patients with ureteric calculi. MET is a reasonable option for conservative management of ureteric calculi that may avoid the need for surgical intervention. The greatest benefit is likely seen with alpha-blockers and calculi ≥5 mm in the distal ureter. Expanding indications for the use of MET include facilitating stone fragment clearance after SWL. MET appears to be safe for use in pregnant and pediatric patients.

Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART II.

PURPOSE: This Guideline is intended to provide a clinical framework for the surgical management of patients with kidney and/or ureteral stones. The summary presented herein represents Part II of the two-part series dedicated to Surgical Management of Stones: American Urological Association/Endourological Society Guideline. Please refer to Part I for introductory information and a discussion of pre-operative imaging and special cases. MATERIALS AND METHODS: A systematic review of the literature (search dates 1/1/1985 to 5/31/2015) was conducted to identify peer-reviewed studies relevant to the surgical management of stones. The review yielded an evidence base of 1,911 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional directives are provided as Clinical Principles and Expert Opinions when insufficient evidence existed. RESULTS: The Panel identified 12 adult Index Patients to represent the most common cases seen in clinical practice. Three additional Index Patients were also created to describe the more commonly encountered special cases, including pediatric and pregnant patients. With these patients in mind, Guideline statements were developed to aid the clinician in identifying optimal management. CONCLUSIONS: Proper treatment selection, which is directed by patient- and stone-specific factors, remains the greatest predictor of successful treatment outcomes. This Guideline is intended for use in conjunction with the individual patient's treatment goals. In all cases, patient preferences and personal goals should be considered when choosing a management strategy.

Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART I.

PURPOSE: This Guideline is intended to provide a clinical framework for the surgical management of patients with kidney and/or ureteral stones. The summary presented herein represents Part I of the two-part series dedicated to Surgical Management of Stones: American Urological Association/Endourological Society Guideline. Please refer to Part II for an in-depth discussion of patients presenting with ureteral or renal stones. MATERIALS AND METHODS: A systematic review of the literature (search dates 1/1/1985 to 5/31/2015) was conducted to identify peer-reviewed studies relevant to the surgical management of stones. The review yielded an evidence base of 1,911 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional directives are provided as Clinical Principles and Expert Opinions when insufficient evidence existed. RESULTS: The Panel identified 12 adult Index Patients to represent the most common cases seen in clinical practice. Three additional Index Patients were also created to describe pediatric and pregnant patients with such stones. With these patients in mind, Guideline statements were developed to aid the clinician in identifying optimal management. CONCLUSIONS: Proper treatment selection, which is directed by patient- and stone-specific factors, remains the greatest predictor of successful treatment outcomes. This Guideline is intended for use in conjunction with the individual patient's treatment goals. In all cases, patient preferences and personal goals should be considered when choosing a management strategy.

A population based study of the changing demographics of patients undergoing definitive treatment for kidney stone disease.

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.

The surgical management of kidney stone disease: a population based time series analysis.

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, and 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.

The role of prophylactic versus selective ureteric stenting in kidney transplant patients: a retrospective review.

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.

A prospective study examining the incidence of bacteriuria and urinary tract infection after shock wave lithotripsy with targeted antibiotic prophylaxis.

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.

Exploring the role of miRNAs in renal cell carcinoma progression and metastasis through bioinformatic and experimental analyses.

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.

A Machine Learning Approach to Predict the Outcome of Urinary Calculi Treatment Using Shock Wave Lithotripsy: Model Development and Validation Study.

BACKGROUND: Shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy are established treatments for renal stones. Historically, SWL has been a predominant and commonly used procedure for treating upper tract renal stones smaller than 20 mm in diameter due to its noninvasive nature. However, the reported failure rate of SWL after one treatment session ranges from 30% to 89%. The failure rate can be reduced by identifying candidates likely to benefit from SWL and manage patients who are likely to fail SWL with other treatment modalities. This would enhance and optimize treatment results for SWL candidates. OBJECTIVE: We proposed to develop a machine learning model that can predict SWL outcomes to assist practitioners in the decision-making process when considering patients for stone treatment. METHODS: A data set including 58,349 SWL procedures performed during 31,569 patient visits for SWL to a single hospital between 1990 and 2016 was used to construct and validate the predictive model. The AdaBoost algorithm was applied to a data set with 17 predictive attributes related to patient demographics and stone characteristics, with success or failure as an outcome. The AdaBoost algorithm was also applied to a training data set. The generated model's performance was compared to that of 5 other machine learning algorithms, namely C4.5 decision tree, naïve Bayes, Bayesian network, K-nearest neighbors, and multilayer perceptron. RESULTS: The developed model was validated with a testing data set and performed significantly better than the models generated by the other 5 predictive algorithms. The sensitivity and specificity of the model were 0.875 and 0.653, respectively, while its positive predictive value was 0.7159 and negative predictive value was 0.839. The C-statistics of the receiver operating characteristic (ROC) analysis was 0.843, which reflects an excellent test. CONCLUSIONS:  We have developed a rigorous machine learning model to assist physicians and decision-makers to choose patients with renal stones who are most likely to have successful SWL treatment based on their demographics and stone characteristics. The proposed machine learning model can assist physicians and decision-makers in planning for SWL treatment and allow for more effective use of limited health care resources and improve patient prognoses.

A clinical nomogram to predict the successful shock wave lithotripsy of renal and ureteral calculi.

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 Lithotron® lithotripter. RESULTS: A total of 422 patients (69.7% male) were analyzed. Mean stone size was 52.3±39.3 mm2 for ureteral stones and 78.9±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.

miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation.

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.

Predictors of health-related quality of life recovery following laparoscopic simple, radical and donor nephrectomy.

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 χ² 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/m² (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.

Clips Can be Safely Used for Vascular Control of the Renal Vessels During Laparoscopic Donor Nephrectomy.

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.

Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs.

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.

The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma.

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.