Initial Observation of a Large Proportion of Patients Presenting with Clinical Stage T1 Renal Masses: Results from the MUSIC-KIDNEY Statewide Collaborative

Background: While surgical excision remains the principal management strategy for clinical T1 renal masses (cT1RMs), the rates of noninterventional approaches are not well known. Most single-institution and population-based series suggest rates below 10%. Objective: To evaluate the use of observation for newly diagnosed cT1RM patients in academic and community-based practices across a statewide collaborative. Design, setting, and participants: The Michigan Urological Surgery Improvement Collaborative—Kidney mass: Identifying and Defining Necessary Evaluation and therapY (MUSIC-KIDNEY) commenced data collection in September 2017 by re-cording clinical, radiographic, pathologic, and short-term follow-up data for cT1RMpatients at 13 diverse practices. Patients with complete data were assessed at \u3e90 dafter initial evaluation as to whether observation or treatment was performed. Outcome measurements and statistical analysis: Relationships with outcomes were analyzed using multivariable logistic regression, chi-square test, and Wilcoxon rank-sum test. Results and limitations: Out of 965 patients, observation was employed in 48%(n = 459), with practice-level rates ranging from 0% to 68%. Patients managed with observation (vs treatment) were significantly older (71.2 vs 62.8 yr, p \u3c 0.0001) and had smaller tumors (2.3 vs 3.4 cm, p \u3c 0.0001). Observation was used for 53.5% of cT1a renal masses, for 29.9% of cT1b renal masses, and for 42.5%, 53.7%, and 63.9% of radiographically solid, Bosniak III–IV cystic, and indeterminate cT1RMs, respectively. Factors significantly associated with observation in multivariable analysis included lesion type (Bosniak III–IV vs solid, p = 0.017), tumor stage (cT1a vs cT1bp \u3c 0.001), and higher age (p \u3c 0.001). A short duration of follow-up limits the assessment of longer-term patient management. Conclusions: Noninterventional management of cT1RMs is common across the MUSIC-KIDNEY collaborative, with wide variability across practices. Factors associated with observation were advanced age, smaller tumor size, and cystic tumor type. Durability of the initial decision for observation (delayed intervention vs. active surveillance vs less active surveillance) will be a focus of subsequent study. Patient summary: The Michigan Urological Surgery Improvement Collaborative: Kidney mass: Identifying and Defining Necessary Evaluation and therapY (MUSIC-KIDNEY) quality improvement collaborative assessed the current utilization of initial observation of a renal mass 7 cm across a diverse group of urology practices and found it to be used in 48% of patients. We found that the factors predicting observation were advanced age, smaller tumor size, and cystic tumor type

Biomechanics and anterior cruciate ligament reconstruction

For years, bioengineers and orthopaedic surgeons have applied the principles of mechanics to gain valuable information about the complex function of the anterior cruciate ligament (ACL). The results of these investigations have provided scientific data for surgeons to improve methods of ACL reconstruction and postoperative rehabilitation. This review paper will present specific examples of how the field of biomechanics has impacted the evolution of ACL research. The anatomy and biomechanics of the ACL as well as the discovery of new tools in ACL-related biomechanical study are first introduced. Some important factors affecting the surgical outcome of ACL reconstruction, including graft selection, tunnel placement, initial graft tension, graft fixation, graft tunnel motion and healing, are then discussed. The scientific basis for the new surgical procedure, i.e., anatomic double bundle ACL reconstruction, designed to regain rotatory stability of the knee, is presented. To conclude, the future role of biomechanics in gaining valuable in-vivo data that can further advance the understanding of the ACL and ACL graft function in order to improve the patient outcome following ACL reconstruction is suggested

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.

BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma

“My bladder is hanging out of my anus”: Successful Management of First Reported Case of Male Transanal Bladder Prolapse

We present a case of an 81-year-old man who presented with a large recto-urethral fistula resulting in prolapsing bladder through the anus. A multi-disciplinary approach with urology, colorectal surgery and plastic surgery was utilized for management of the prolapse with excellent postoperative result. This unique scenario enabled a transanal cystoprostatectomy; the procedure was completed using a natural orifice without transabdominal surgery

Development of a Novel Scoring System Quantifies Opportunities to Reduce Surgery for Benign Renal Neoplasms: A Retrospective Quality Improvement Analysis within the MUSIC KIDNEY Collaborative

PURPOSE: Non-malignant pathology (NMP) has been reported in 15-20% of surgeries for cT1 renal masses (cT1RM). We seek to identify opportunities for improvement in avoiding surgery for NMP. MATERIALS AND METHODS: MUSIC-KIDNEY started collecting data in 2017. All cT1RM patients who had partial (PN) or radical (RN) nephrectomy for NMP were identified. Category for improvement (none=0, minor=1, moderate=2, or major=3) was independently assigned to each case by five experienced kidney surgeons. Specific strategies to decrease NMP were identified. RESULTS: Of 1392 patients with cT1RM, 653 underwent surgery and 74 had NMP (11%). Of these, 23 (31%) were cT1b. RN was performed in 17 (22.9%) patients for 5 cT1a and 12 cT1b lesions. Only 6 patients had a biopsy prior to surgery (5 oncocytoma, 1 unclassified RCC). Review identified 25 cases with minor (34%), 26 with moderate (35%), and 10 with major (14%) QI opportunities. 17% of cases had no QI opportunities identified (12 PN, 1 RN). CONCLUSIONS: Review of cT1RM patients who underwent surgery for NMP revealed a significant number of cases in which this outcome may have been avoided. Approximately half of cases had moderate or major QI opportunities, with RN for NMP being the most common reason. Our data indicate a lowest achievable and acceptable rate of NMP to be 1.9% and 5.4% respectively. Avoiding interventions for NMP, particularly RN, is an important focus of QI efforts. Strategies to decrease unnecessary interventions for NMP include greater use of repeat imaging, renal mass biopsy, and surveillance

Initial Management of Indeterminate Renal Lesions in a Statewide Collaborative: A MUSIC-KIDNEY Analysis

PURPOSE: Renal masses can be characterized as indeterminate due to lack of differentiating imaging characteristics. Optimal management of indeterminate renal lesions remains nebulous and poorly defined. We assess management of indeterminate renal lesions within the MUSIC-KIDNEY (Michigan Urological Surgery Improvement CollaborativeKidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative. MATERIALS AND METHODS: Each renal mass is classified as suspicious, benign, or indeterminate based on radiologist and urologist assessment. Objectives were to assess initial management of indeterminate renal lesions and the impact of additional imaging and biopsy on characterization prior to treatment. RESULTS: Of 2,109 patients, 444 (21.1%) had indeterminate renal lesions on their initial imaging, which included CT without contrast (36.2%), CT with contrast (54.1%), and MRI (9.7%). Eighty-nine patients (20.0%) underwent additional imaging within 90 days, 8.3% (37/444) underwent renal mass biopsy, and 3.6% (16/444) had reimaging and renal mass biopsy. Additional imaging reclassified 58.1% (61/105) of indeterminate renal lesions as suspicious and 21.0% (22/105) as benign, with only 20.9% (22/105) remaining indeterminate. Renal mass biopsy yielded a definitive diagnosis for 87%. Treatment was performed for 149 indeterminate renal lesions (33.6%), including 117 without reimaging and 123 without renal mass biopsy. At surgery for indeterminate renal lesions, benign pathology was more common in patients who did not have repeat imaging (9.9%) than in those who did (6.7%); for ≤4 cm indeterminate renal lesions, these rates were 11.8% and 4.3%. CONCLUSIONS: About 33% of patients diagnosed with an indeterminate renal lesion underwent immediate treatment without subsequent imaging or renal mass biopsy, with a 10.1% rate of nonmalignant pathology. This highlights a quality improvement opportunity for patients with cT1 renal masses: confirmation that the lesion is suspicious for renal cell carcinoma based on high-quality, multiphase, cross-sectional imaging and/or histopathological features prior to surgery, even if obtaining subsequent follow-up imaging and/or renal mass biopsy is necessary. When performed, these steps lead to reclassification in 79% and 87% of indeterminate renal lesions, respectively