Jason Y. Lee

Stone Attenuation and Skin-to-Stone Distance on Computed Tomography Predicts for Stone Fragmentation by Shock Wave Lithotripsy

OBJECTIVESnTo determine whether stone attenuation and the skin-to-stone distance (SSD) can predict for stone fragmentation by SWL independently. Identifying the factors predictive of shock wave lithotripsy (SWL) outcome would help streamline the care of patients with stones.nnnMETHODSnA retrospective review was performed of 111 patients undergoing initial SWL for a solitary, 5-20 mm, renal calculus. Stone size, location, attenuation value, and SSD were determined on pretreatment noncontrast computed tomography. The outcome was categorized as stone free, complete fragmentation <5 mm, and incomplete fragmentation >or=5 mm or unchanged at 2 weeks on kidney/ureter/bladder radiography.nnnRESULTSnAfter SWL, 44 (40%) were stone free, 27 (24%) had complete fragmentation, and 40 (36%) of 111 patients had incomplete fragmentation. The stone attenuation of the successfully treated patients (stone free and complete fragmentation groups) was 837 +/- 277 Hounsfield units (HU) vs 1092 +/- 254 HU for those with treatment failure (incomplete fragmentation; P < .01). The mean SSD also differed: 9.6 cm +/- 2.0 vs 11.1 cm +/- 2.5 for the successful treatment group vs the treatment failure group, respectively (P = .01). On multivariate analysis, the factors that independently predicted the outcome were stone attenuation, SSD, and stone composition. When patients were stratified into 4 risk groups (stone <900 HU and SSD <9.0 cm, stone <900 HU and SSD >or=9.0 cm, stone >or=900 HU and SSD <9.0 cm, and stone >or=900 HU and SSD >or=9.0 cm), the SWL success rate was 91%, 79%, 58%, and 41%, respectively (odds ratio 7.1, 95% confidence interval 1.6-32 for <900 HU and SSD <9.0 cm group vs other 3 risk groups; P = .01).nnnCONCLUSIONSnThe results of our study have shown that a stone attenuation of <900 HU, SSD of <9 cm, and stone composition predict for SWL success, independent of stone size, location, and body mass index. These factors will be considered important in the prospective design of a SWL treatment nomogram at our center.

High Fidelity Simulation Based Team Training in Urology: A Preliminary Interdisciplinary Study of Technical and Nontechnical Skills in Laparoscopic Complications Management

PURPOSEnSimulation based team training provides an opportunity to develop interdisciplinary communication skills and address potential medical errors in a high fidelity, low stakes environment. We evaluated the implementation of a novel simulation based team training scenario and assessed the technical and nontechnical performance of urology and anesthesiology residents.nnnMATERIALS AND METHODSnUrology residents were randomly paired with anesthesiology residents to participate in a simulation based team training scenario involving the management of 2 scripted critical events during laparoscopic radical nephrectomy, including the vasovagal response to pneumoperitoneum and renal vein injury during hilar dissection. A novel kidney surgical model and a high fidelity mannequin simulator were used for the simulation. A debriefing session followed each simulation based team training scenario. Assessments of technical and nontechnical performance were made using task specific checklists and global rating scales.nnnRESULTSnA total of 16 residents participated, of whom 94% rated the simulation based team training scenario as useful for communication skill training. Also, 88% of urology residents believed that the kidney surgical model was useful for technical skill training. Urology resident training level correlated with technical performance (p=0.004) and blood loss during renal vein injury management (p=0.022) but not with nontechnical performance. Anesthesia resident training level correlated with nontechnical performance (p=0.036). Urology residents consistently rated themselves higher on nontechnical performance than did faculty (p=0.033). Anesthesia residents did not differ in the self-assessment of nontechnical performance compared to faculty assessments.nnnCONCLUSIONSnResidents rated the simulation based team training scenario as useful for interdisciplinary communication skill training. Urology resident training level correlated with technical performance but not with nontechnical performance. Urology residents consistently overestimated their nontechnical performance.

Low expression of miR-126 is a prognostic marker for metastatic clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with unpredictable behavior. Clinical parameters are not always accurate for predicting prognosis. miR-126 is differentially expressed in many cancers, including RCC, and is down-regulated in metastatic versus primary ccRCC. We assessed the prognostic significance of miR-126 in 264 primary ccRCCs. We also compared its expression in normal kidney, primary and metastatic ccRCC, and RCC subtypes. We validated our results on an independent set of 481 ccRCCs. miR-126 was down-regulated in metastatic versus primary tumors and in tumors of higher stage (Pxa0=xa00.005) or higher grade (Pxa0=xa00.002). miR-126 up-regulation was associated with significantly prolonged disease-free survival (Pxa0<xa00.001) and overall survival (Pxa0=xa00.015). For larger tumors (>4 cm), patients with higher miR-126 expression had significantly longer survival. Restoration of miR-126 expression decreased cellular migration and proliferation in RCC cell lines. The ccRCCs exhibited the highest miR-126 expression, and papillary RCCs exhibited the lowest expression. We identified a number of miR-126 targets and pathways that are involved in carcinogenesis, including the apoptosis signaling pathway. miR-126 is a promising prognostic marker in ccRCC that can distinguish between clear cell and papillary subtypes. In addition, miR-126 has potential therapeutic applications.

Profilin-1 expression is associated with high grade and stage and decreased disease-free survival in renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is associated with high mortality, although individual outcomes are highly variable. Identification of patients with increased risk of disease progression can guide customizing management plan according to disease severity. Profilin-1 (Pfn1) has been recently identified as overexpressed in metastatic ccRCC compared with primary tumors. We examined Pfn1 expression in a tissue microarray of 384 cases of histologically confirmed primary ccRCC with detailed clinical follow-up. Profilin-1 expression showed both cytoplasmic and nuclear staining patterns. The immunoexpression of Pfn1 was scored in a semiquantitative fashion. There was no significant difference in Pfn1 expression between normal kidney and kidney ccRCC. Our results show that strong cytoplasmic Pfn1 expression is associated with high-grade (P < .001) and high-stage (III-IV) (P = .018) disease. Univariate analysis of the data set showed that higher Pfn1 expression is associated with significantly shorter disease-free survival (hazard ratio 7.36, P = .047) and also lower overall survival. Kaplan-Meier analysis showed that high cytoplasmic expression of Pfn1 was also associated with a statistically significant lower disease-free survival (P = .018). It was also associated with lower overall survival, although this was not statistically significant. Profilin-1 lost its prognostic significance in the multivariate analysis when controlling for grade and stage. Profilin-1 expression was not associated with significant prognostic deference in the subgroup of patients with stage 1 disease. Our results suggest that the evaluation of Pfn1 by immunohistochemistry may help to identify patients with an increased risk of disease progression. We validated our results at the messenger RNA level on an independent patient cohort. Higher messenger RNA expression of Pfn1 is associated with significantly lower survival.

Exosomal MicroRNAs Are Diagnostic Biomarkers and Can Mediate Cell–Cell Communication in Renal Cell Carcinoma

BACKGROUNDnApart from an invasive biopsy, currently no tools are available to confirm the diagnosis of clear cell renal cell carcinoma (ccRCC); this resulted in approximately 30% of patients being diagnosed with metastatic disease.nnnOBJECTIVEnTo determine whether urinary microRNAs (miRNAs) can serve as biomarkers to confirm the diagnosis of ccRCC.nnnDESIGN, SETTING, AND PARTICIPANTSnGlobal miRNA expression was assessed in 28 preoperative urine samples from patients with ccRCC and 18 healthy participants. The independent validation set consisted of 81 ccRCC patients, 24 patients with benign lesions, and 33 healthy participants. We extracted both cell-free and exosomal RNA for miRNA expression analysis using miRNA-specific polymerase chain reaction assays. We also investigated exosomal miRNA secretion in cell line models and performed exosome transfer between RCC and endothelial cell types.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnReceiver operating characteristic analysis was applied to identify the discrimination power of miRNAs.nnnRESULTS AND LIMITATIONSnOverall, miR-126-3p combined with miR-449a or with miR-34b-5p could significantly distinguish ccRCC patients from healthy participants (miR-126-3p-miR-449a: area under the curve [AUC]: 0.84; 95% confidence interval [CI], 0.7620-0.9151; p<0.001; miR-126-3p-miR-34b-5p: AUC: 0.79; 95% CI, 0.7013-0.8815; p<0.001). The combination of miR-126-3p and miR-34b-5p was also able to distinguish small renal masses (pT1a, ≤4cm) from healthy controls (AUC: 0.79; 95% CI, 0.6848-0.8980; p<0.001). Using miR-126-3p and miR-486-5p in combination, we were able to differentiate between benign lesions and ccRCC (AUC: 0.85; 95% CI, 0.7295-0.9615; p<0.01). The expression of a number of miRNAs returned to a level comparable with health after surgery. Kidney cancer cell lines were found to secrete exosomal miR-126-3p, miR-17-5p, miR-21-3p, and miR-25-3p, and these miRNAs were found to be internalized by other cell types.nnnCONCLUSIONSnWe identified exosomal miRNAs as potential noninvasive diagnostic urinary biomarkers for ccRCC and provided evidence that miRNAs are secreted by the tumor and can function as a tool for intercellular communication.nnnPATIENT SUMMARYnWe identified urinary microRNAs that can serve as diagnostic biomarkers for clear cell renal cell carcinoma.

Surgical Skills Acquisition Among Left-Handed Trainees—True Inferiority or Unfair Assessment: A Preliminary Study

INTRODUCTIONnStudies involving the formal assessment of surgical skills have often reported inferior abilities among left-handed surgical trainees (LHT). Most surgical training curricula and assessment methods, however, are inherently geared toward right-handed trainees (RHT); potentially placing LHT at both a training and assessment disadvantage. We evaluated the effect of a hand dominance-based curriculum for acquisition of basic suturing and knot tying skills among medical students.nnnMETHODSnAfter Institutional Review Board approval, first- and second-year medical students from the University of California, Irvine School of Medicine were recruited to participate in a basic suturing and knot tying skills course. Consenting students were randomized to either a left-handed curriculum or a right-handed curriculum consisting of (1) a 30-minute introductory video and (2) a 2-hour instructor-led, hands-on training session on basic suturing and knot tying. All instructional methods, instruments, and instructors were exclusively right-handed or left-handed for the right-handed curriculum or left-handed curriculum, respectively. Students were assessed on the performance of 2 suturing tasks, continuous running suturing and instrument knot tying, and performance assessments were conducted both immediately and 2 weeks posttraining.nnnRESULTSnA total of 19 students completed the training course and both assessments (8 LHT, 11 RHT). Students randomized to a curriculum concordant with their hand dominance performed significantly better than those randomized to a discordant curriculum on both tasks (p < 0.01). This difference was found at both immediate and 2 weeks posttraining assessments. Within concordant and discordant groups, there were no significant differences between LHT and RHT.nnnCONCLUSIONSnThis preliminary study demonstrates that medical students, both LHT and RHT, immersed in a training environment that is discordant with their hand dominance might have inferior acquisition of basic suturing and knot tying skills.

Medical Expulsive Therapy: Worthwhile or Wishful Thinking

Purpose of ReviewWe 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 FindingsThe 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.SummaryMET 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 ≥5xa0mm 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.

Dual usage of a stone basket: Stone capture and retropulsion prevention

INTRODUCTIONnStone migration during ureteroscopy (URS) for proximal ureteric calculi is a constant challenge. Several retropulsion prevention devices have been developed to optimize URS outcomes. Our technique involves capturing the stone within a four-wire Nitinol stone basket and then performing laser lithotripsy to dust the stone while it is engaged in the basket. The dusted fragments wash out with the irrigation fluid and once small enough, the remaining stone is removed intact.nnnMETHODSnA retrospective chart review was performed of all proximal semi-rigid URS procedures for a solitary calculus (2000-2016). We compared our new technique introduced in 2010 to URS control procedures that did not use retropulsion prevention techniques or devices.nnnRESULTSnOne hundred and forty patients underwent URS for proximal ureteric calculi. Mean stone diameter was 9.3±3.4 mm, with similar impaction rate between both groups (44.1% vs. 43.1% control; p=n/s). The mean surgical procedure time was 53.3±17.9 minutes for the new technique and 65.2±29.2 minutes for the control group (p=0.005). Compared to the new technique, the control group had a higher rate of retropulsion (33.3% vs. 14.7%; p=0.01) and required flexible URS more often to exclude or remove residual fragments (24.1% vs. 59.1%; p=0.001). Using the new technique, stone-free rates were higher (79.1% vs. 69.4%; p=n/s) and there was a lower likelihood of leaving residual fragments both <3 mm and ≥3 mm (p=0.001).nnnCONCLUSIONSnOur novel technique results in shorter operative times, lower retropulsion rates, and decreases postoperative residual stone fragments.

The role of thrombectomy and diffusion-weighted imaging with MRI in post-transplant renal vein thrombosis: a case report

BackgroundSurgical thrombectomy in the context of acute renal vein thrombosis (RVT) post-transplantation has had limited success, with considerable variation in the surgical techniques used. Unfortunately, it is usually followed by allograft nephrectomy within a few days if rapid allograft recovery does not ensue. We report a case of acute RVT in which nephrectomy was not performed despite a prolonged requirement for dialysis post-thrombectomy, but with recovery of renal function 2 weeks later. We also report the findings of serial MRI with diffusion-weighted imaging (DW-MRI) throughout the patient’s recovery, which provided novel insights into allograft microvascular perfusion changes post-thrombectomy.Case presentationA 65-year old patient underwent living-unrelated kidney transplantation complicated by acute RVT. Surgical thrombectomy and irrigation led to a delayed, but significant, recovery of renal function. Serial non-contrast DW-MRI scanning was used to non-invasively assess microvascular renal blood flow post-operatively. Unlike standard Doppler ultrasonography, DW-MRI documented reduced microvascular perfusion initially, with gradual but incomplete recovery that mirrored the partial improvement in renal function.ConclusionsOur findings suggest that surgical thrombectomy may be more effective than previously described if followed by careful patient observation. Moreover, diffusion-weighted MRI appears to provide important insights into the pathophysiology of delayed graft function and deserves further investigation.