Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men.

BACKGROUND: Prostate-specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening. METHODS: To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent PSA screening at 3 months (primary outcome), a randomized trial of FH versus GRS plus FH was conducted with 700 whites aged 40 to 49 years without prior PSA screening. Secondary outcomes included anxiety, recall, physician discussion at 3 months, and PSA screening at 3 years. Pictographs versus numeric presentations of genetic risk were also evaluated. RESULTS: At 3 months, no significant differences were observed in the rates of PSA screening between the FH arm (2.1%) and the GRS-FH arm (4.5% with GRS-FH vs. 2.1% with FH: χ2 = 3.13, P = .077); however, PSA screening rates at 3 months significantly increased with given risk in the GRS-FH arm (P = .013). Similar results were observed for discussions with physicians at 3 months and PSA screening at 3 years. Average anxiety levels decreased after the individual cancer risk was provided (P = .0007), with no differences between groups. Visual presentation by pictographs did not significantly alter comprehension or anxiety. CONCLUSIONS: This is likely the first randomized trial of multimarker genomic testing to report genomic targeting of cancer screening. This study found little evidence of concern about excess anxiety or overuse/underuse of PSA screening when multimarker genetic risks were provided to patients. Cancer 2016;122:3564-3575. © 2016 American Cancer Society.

Functional Duration of Closure Systems Used in Partial Nephrectomy.

PURPOSE: We determined the functional life of various configurations of partial nephrectomy closure systems. MATERIALS AND METHODS: Sutures were prepared using standard techniques for sutured renorrhaphy during partial nephrectomy. Tested systems included knot/Hem-o-Lok®, Lapra-Ty®/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok combinations. The saline filled tank was maintained at 37C. Vicryl®, Stratafix™ polyglycolic acid-polycaprolactone or V-Loc™ 180 sutures were suspended at 4 or 2 N. Suture material breakage or slippage was considered failure. RESULTS: At 4 N 20% of sutures terminated with knot/Hem-o-Lok failed by 3 weeks compared to 56% and 100% terminated with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively (p <0.0001). The 55% and 100% of failures with Lapra-Ty/Hem-o-Lok and Hem-o-Lok/Hem-o-Lok, respectively, were generally due to slippage vs 11% with knot/Hem-o-Lok (p <0.0001). Overall failure rates with Lapra-Ty/Hem-o-Lok for zero to 4-zero sutures were 41% with Vicryl, 82% with polyglycolic acid-polycaprolactone and 24% with V-Loc 180 (p <0.0001). The only sutures without failure at 4 N with Lapra-Ty/Hem-o-Lok and knot/Hem-o-Lok closure systems were Vicryl zero, and V-Loc 2-zero and 3-zero. At 2 N Lapra-Ty/Hem-o-Lok failure (17.5% vs 0%, p = 0.039) and Hem-o-Lok/Hem-o-Lok failure (39% vs 16%, p = 0.074) were more common with polyglycolic acid-polycaprolactone than with V-Loc sutures. CONCLUSION: Hem-o-Lok/Hem-o-Lok and Lapra-Ty/Hem-o-Lok combinations resulted in more frequent failures at 3 weeks or greater than knot/Hem-o-Lok. For all sutures tested knots were superior to Lapra-Tys to backstop Hem-o-Loks at 4 N. Preferably, Vicryl zero or V-Loc 2-zero/3-zero sutures should be used in combination with knots or Lapra-Tys at 4 N. Under these experimental conditions the Lapra-Ty/Hem-o-Lok combination did not reliably suspend the other sutures tested for 3 weeks. If Lapra-Ty/Hem-o-Lok or Hem-o-Lok/Hem-o-Lok combinations are used, we recommend closure at lesser tension and/or the use of appropriate sutures.

Proteinuria is a Predictor of Renal Functional Decline in Patients with Kidney Cancer.

PURPOSE: Prior studies have shown that 26% to 34% of patients with suspected renal cancers have a glomerular filtration rate less than 60 ml/minute/1.73 m(2) but limited information exists regarding proteinuria. We investigated the extent of proteinuria in patients with renal tumors to determine the impact on the classification and progression of chronic kidney disease. MATERIALS AND METHODS: Among 1,622 patients evaluated between 1999 and 2014, 1,016 had preoperative creatinine and proteinuria measurements available. Patients were classified according to the risk of chronic kidney disease progression into low, moderately increased, high and very high risk groups according to 2012 KDIGO guidelines. Predictors of risk group and chronic kidney disease progression were analyzed using univariable and multivariate models. RESULTS: Before treatment 32% had a glomerular filtration rate less than 60 ml/minute/1.73 m(2). Preoperative proteinuria was present in 22%. Proteinuria was detected in 30% with a reduced glomerular filtration rate and 18% with a normal glomerular filtration rate. Among the 44% at increased risk for chronic kidney disease progression 24%, 12% and 8% were at moderately increased, high and very high risk, respectively. The presence of proteinuria also reclassified 25% with stage III chronic kidney disease as high or very high risk. KDIGO classification predicted renal functional decline, which occurred in 2.2%, 4.4%, 9.4% and 34.6% at 3 years in low, moderately increased, high and very high risk categories, respectively. Predictors of KDIGO group included age and tumor size (each p <0.001), and the main predictors of renal functional decline were KDIGO group, tumor size and radical nephrectomy (each p <0.0001). CONCLUSIONS: Identification of chronic kidney disease using only glomerular filtration rate left 18% of patients undiagnosed. The assessment of glomerular filtration rate and proteinuria classified patients according to risk of chronic kidney disease progression, identifying 44% to be at increased risk. As proteinuria predicted renal functional decline, we advocate for routine evaluation before treatment.

Impact of Reduced Glomerular Filtration Rate and Proteinuria on Overall Survival of Patients with Renal Cancer.

PURPOSE: Although it is commonly staged according to glomerular filtration rate, an international work group recommended classifying chronic kidney disease by cause, glomerular filtration rate and albuminuria. Data on nonsurgical patients with chronic kidney disease indicate proteinuria to be an independent predictor of renal function decrease and mortality. We evaluated whether preoperative proteinuria impacted survival in patients undergoing nephrectomy. MATERIALS AND METHODS: An institutional registry was queried for information regarding preoperative creatinine/glomerular filtration rate and urinalysis in 900 patients, including 362 and 538 treated with partial and radical nephrectomy, respectively. Patients were grouped according to glomerular filtration rate level (G1 to G5), proteinuria level (A1 to A3) and chronic kidney disease risk classification (low to very high). Kaplan-Meier and Cox proportional hazards analyses of overall survival were performed. RESULTS: The preoperative glomerular filtration rate was less than 60 ml/minute/1.73 m(2) in 30% of patients (median 73, IQR 56-91) and 20% of patients had baseline proteinuria. According to the KDIGO (Kidney Disease Improving Global Outcomes) classification 23% of patients were at moderately increased, 11% were at high and 8% were at very high risk for chronic kidney disease progression. Kaplan-Meier analysis revealed that the preoperative glomerular filtration rate, proteinuria and chronic kidney disease risk group were associated with poor overall survival. In Cox proportional hazard models accounting for age, gender, race, tumor size, clinical stage and surgery type the glomerular filtration rate, proteinuria and chronic kidney disease risk group were highly significant predictors of overall survival (p <0.0001). CONCLUSIONS: Preoperative proteinuria is a significant predictor of overall survival in patients who undergo nephrectomy. Classification according to preoperative glomerular filtration rate and proteinuria more accurately predicts survival than using the glomerular filtration rate alone after accounting for cancer stage. This information supports routine evaluation of proteinuria in patients with kidney cancer.

Renal angiomyolipoma: preoperative identification of atypical fat-poor AML.

The preoperative distinction between benign and malignant renal masses is a well-known radiographic diagnostic challenge. With angiomyolipoma (AML) and renal cell carcinoma (RCC) representing the most common benign and malignant renal parenchymal lesions, respectively, differentiating these two entities is especially important due to their vastly different treatments and prognoses. Renal AML is typically composed of smooth muscle cells, dysmorphic blood vessels, and varying amounts of adipose tissue. In most cases, "typical" AML can be diagnosed by identifying macroscopic fat with ultrasound, computed tomography, or magnetic resonance imaging. However, approximately 4-5 % of AML tumors have fat that is grossly undetectable by conventional techniques, precluding a straightforward diagnosis. The overlapping radiographic features between "atypical" or "fat-poor" AML and RCC, especially in smaller (<3-4 cm) lesions, lead many patients with benign AML to undergo unnecessary surgery for suspected RCC when the diagnosis is not established beforehand. This review presents the most recent studies and developments in preoperative evaluation of fat-poor AML.

Holding Strength of a Hem-o-lok/Lapra-Ty Clip Combination on Sutures Used During Partial Nephrectomy.

OBJECTIVE: To investigate the anti-slip strength of closing systems employing sutures terminated with a Hem-o-lok/Lapra-Ty clip combination to determine which sutures perform best for this application. Partial nephrectomy is the reference standard for treatment of small renal masses. The main disadvantage of partial nephrectomy is the risk of technical complications, including renorrhaphy site bleeding and urine leak. MATERIALS AND METHODS: A materials testing system produced a constant velocity pull on the free end of an anchored suture. A Lapra-Ty clip was attached 1 cm from the end of each suture as a backstop for the Hem-o-lok. A digital force gauge measured the tension that was applied until the suture slipped in the closing system. Vicryl, Monocryl, Chromic, Stratafix, and V-Loc sutures of diameters 1 to 4-0 were tested (n = 7 for each suture type, 161 total experiments). RESULTS: The holding strength of a Lapra-Ty/Hem-o-lok clip combination is lowest for Vicryl 4-0 (4.3 ± 1.4N) and highest for Monocryl 0 (16.5 ± 1.6N) sutures. Larger sutures (1 and 0) hold at higher tensions than sutures with smaller dimensions (4-0 and 3-0). For 2-0 sutures, the holding strength was 5.7N with Vicryl, 13.8N with Stratafix, and 15.9N with V-Loc sutures. CONCLUSION: The mean values of holding tension of this anchoring system for all sutures tested was greater than the amount found to be sufficient for tissue closure in previous studies (3.2N). Barbed sutures (Stratafix, V-Loc) appeared to have superior holding strength when compared with most standard sutures; barb orientation does not influence holding tension.

Robotic Buccal Mucosal Graft Ureteroplasty for Complex Ureteral Stricture.

OBJECTIVE: To demonstrate robot-assisted ureterolysis and buccal mucosal graft (BMG) ureteroplasty for the management of a complex, long recurrent ureteral stricture developing after ureterolysis, and also to demonstrate the use of near-infrared fluorescence (NIRF) imaging and intraoperative ureteroscopy during this procedure. METHODS: A 58-year-old man with a history of cabergoline treatment and a cardiac catheterization through the left groin presented with left flank pain and hydronephrosis. A computed tomography scan showed extensive fibrosis around the ureter and a ureteral stricture close to a tortuous left external iliac artery. A computed tomography-guided biopsy showed a benign fibrous tissue around the stricture with no increase in IgG4-expressing plasma cells. A robot-assisted ureterolysis with an omental wrap was performed. One year after the ureterolysis, the patient developed a recurrent ureteral stricture. Retrograde ureterogram showed a long, 6-cm stricture in the upper ureter. For the robotic ureteroplasty, the patient was placed in modified lateral position with port placement similar to the left pyeloplasty. Intraoperative flexible ureteroscopy and NIRF were used to define the distal extent of the stricture. For this, the ureteroscope was advanced until the stricture, and transilluminance of light from the ureteroscope was seen from the robotic camera using Firefly. Ureteral stricture was incised along its length over the ureteroscope. Two BMGs were harvested and sown together to obtain a longer graft. The graft was minimally defatted and brought in the abdomen through one of the ports. The composite graft was then sutured with 4-0 PDS as an onlay graft with the mucosal side facing toward the lumen of the ureter. Ureteroscopy was used to confirm patency, followed by stent placement. NIRF was used to confirm the viability of the ureter and the surrounding tissue. The omental flap was then harvested using a vessel sealer, fixed to the psoas fascia beneath the ureter, and then wrapped over the reconstructed ureter. The omental flap was also tacked to the side of the BMG with a suture to promote blood supply. RESULTS: The procedure was uncomplicated with an operative time of 280 minutes, an estimated blood loss of 75 mL, and an uneventful hospital stay. MAG3 Renal scan after 3 and 6 months of surgery showed no recurrence or obstruction. CONCLUSION: Despite the limitation of being a single case with only a 6-month follow-up, our report shows that robot-assisted BMG is a safe option for the reconstruction of long upper ureteral strictures. This procedure may be a less morbid alternative to an autotransplant and ileal ureter in these patients. However, outcomes need to be studied in a larger series with a longer follow-up.

Preoperative Prediction and Postoperative Surgeon Assessment of Volume Preservation Associated With Partial Nephrectomy: Comparison With Measured Volume Preservation.

OBJECTIVE: To evaluate whether surgeons can predict the percent parenchymal mass that will be preserved by partial nephrectomy (PN) based on preoperative imaging, which could have potential utility for preoperative surgical planning and patient counseling. The proportion of preserved viable parenchyma following PN is the primary determinant of functional recovery. However, direct measurement of parenchymal volume preservation (VP) can be complex and time consuming. MATERIALS AND METHODS: For patients managed with PN at our institution (2007-2014), we randomly selected 45 with a third in each of low, intermediate, or high R.E.N.A.L. complexity groups. All patients had recorded postoperative surgeon assessment of volume preservation (SAVP) and measured VP based on preoperative or postoperative computed tomography. Nine clinical providers predicted VP based solely on review of preoperative imaging while blinded to SAVP and measured VP. Clinical experience of the providers ranged from medical students to experienced urologic surgeons. RESULTS: Median age was 66 years, median tumor size was 4.0 cm, and median R.E.N.A.L. was 8. Median measured VP was 81% (interquartile range of 74-89%). Preoperative prediction of VP correlated poorly with measured VP among the different surgeons (mean correlation coefficient, R = 0.34, range = 0.24-0.40). Surgeon experience provided minimal incremental improvement. Correlation between R.E.N.A.L. and measured VP was also marginal (R = 0.43). In contrast, correlation between postoperative SAVP and measured VP was much more robust (R = 0.75, P <.001). CONCLUSION: Preoperative prediction of VP and R.E.N.A.L. score correlated poorly with measured VP for patients managed with PN. In contrast, postoperative SAVP provided a relatively reliable estimate of VP, and should be considered an acceptable substitute in most clinical circumstances.