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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 (OR male ) = 0.83 [95% CI = 0.78-0.89], P male  = 1.71 × 10 -8 compared with female odds ratio (OR female ) = 0.98 [95% CI = 0.90-1.07], P female  = 0.68) and 12q23.3 (intergenic, OR male  = 0.75 [95% CI = 0.68-0.83], P male  = 1.59 × 10 -8 compared with OR female  = 0.93 [95% CI = 0.82-1.06], P female  = 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.

Objective: To evaluate the accuracy of radius, exophytic/endophytic, nearness to collecting system/sinus, anterior/posterior, and location relative to polar lines (RENAL), preoperative aspects and dimensions used for anatomical classification (PADUA), contact surface area (CSA), and preoperative assessment of volume preservation (PAVP) nephrometry scores in predicting postoperative renal functional outcomes after partial nephrectomy (PN). Few studies have compared the accuracy of tumor complexity systems directly in the same set of PN patients., Materials and Methods: Patients treated with robotic, laparoscopic, or open PN having available imaging (n = 344) were examined. The ability of 4 systems to predict nadir estimated glomerular filtration rate (eGFR [median postoperative day 1]) and new baseline eGFR (median: 0.95 year) was analyzed using univariable and multivariable models., Results: Median preoperative, nadir, and new baseline eGFR were 79 (interquartile range [IQR]: 63-97), 65 (IQR: 47-85), and 80 (IQR: 63-99) mL/min/1.73 m 2 . Multivariable models incorporating RENAL, PADUA, CSA, or PAVP were similarly predictive of postoperative renal function (nadir eGFR: R 2  = 0.683-0.688, new baseline eGFR: R 2  = 0.775). In univariable analysis, all 4 complexity systems were predictors of nadir GFR (each P < .05), with RENAL (P = .045), CSA (P = .027), and PAVP (P = .012) also significantly predicting nadir eGFR in multivariable models. No complexity system was significantly associated with new baseline eGFR in multivariable analysis, with only RENAL (P = .023) and PAVP (P = .049) having a statistically significant association in univariable analysis., Conclusion: RENAL, PADUA, CSA, and PAVP are all predictors of early postoperative renal function. RENAL and PAVP provided the greatest predictive ability for later renal functional outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R 2 >0.5) 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., (Published by Elsevier B.V.)

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10 -10 ), 3p22.1 (rs67311347, P=2.5 × 10 -8 ), 3q26.2 (rs10936602, P=8.8 × 10 -9 ), 8p21.3 (rs2241261, P=5.8 × 10 -9 ), 10q24.33-q25.1 (rs11813268, P=3.9 × 10 -8 ), 11q22.3 (rs74911261, P=2.1 × 10 -10 ) and 14q24.2 (rs4903064, P=2.2 × 10 -24 ). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

Background: Testicular germ cell tumors are the most common cancer diagnosed in young men, and seminomas are the most common type of these cancers. There have been no exome-wide examinations of genes mutated in seminomas or of overall rates of nonsilent somatic mutations in these tumors., Objective: The objective was to analyze somatic mutations in seminomas to determine which genes are affected and to determine rates of nonsilent mutations., Design, Setting, and Participants: Eight seminomas and matched normal samples were surgically obtained from eight patients., Intervention: DNA was extracted from tissue samples and exome sequenced on massively parallel Illumina DNA sequencers. Single-nucleotide polymorphism chip-based copy number analysis was also performed to assess copy number alterations., Outcome Measurements and Statistical Analysis: The DNA sequencing read data were analyzed to detect somatic mutations including single-nucleotide substitutions and short insertions and deletions. The detected mutations were validated by independent sequencing and further checked for subclonality., Results and Limitations: The rate of nonsynonymous somatic mutations averaged 0.31 mutations/Mb. We detected nonsilent somatic mutations in 96 genes that were not previously known to be mutated in seminomas, of which some may be driver mutations. Many of the mutations appear to have been present in subclonal populations. In addition, two genes, KIT and KRAS, were affected in two tumors each with mutations that were previously observed in other cancers and are presumably oncogenic., Conclusions: Our study, the first report on exome sequencing of seminomas, detected somatic mutations in 96 new genes, several of which may be targetable drivers. Furthermore, our results show that seminoma mutation rates are five times higher than previously thought, but are nevertheless low compared to other common cancers. Similar low rates are seen in other cancers that also have excellent rates of remission achieved with chemotherapy., Patient Summary: We examined the DNA sequences of seminomas, the most common type of testicular germ cell cancer. Our study identified 96 new genes in which mutations occurred during seminoma development, some of which might contribute to cancer development or progression. The study also showed that the rates of DNA mutations during seminoma development are higher than previously thought, but still lower than for other common solid-organ cancers. Such low rates are also observed among other cancers that, like seminomas, show excellent rates of disease remission after chemotherapy., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The use of partial nephrectomy and other kidney sparing approaches in national databases lags far behind practice patterns at major academic centers. The reasons and impact of this disparity are largely unknown. We examined the trend in kidney sparing approaches in a community based health care system to examine associated factors and impact on renal function., Materials and Methods: We evaluated the records of all patients who underwent intervention for suspicious renal lesions at a single health care system between 1998 and 2010. Demographic, pathological and functional data were collected in an institutional review board approved database., Results: During the 12 study years a kidney sparing approach was used in 35% of patients with localized renal tumors. A clear increase in the proportion of patients undergoing a kidney sparing approach was observed, including 11%, 23% and 49% during successive 4-year periods. A kidney sparing approach was used in 81% of patients with tumors 4 cm or less during 2009 to 2010. Although high volume (greater than 20 cases annually), more recently graduating (2001 or later) and fellowship trained surgeons had higher kidney sparing approach use overall (each p <0.03), the proportion of patients who underwent a kidney sparing approach increased with time in all study groups (p <0.0001). The renal functional loss in patients who underwent a kidney sparing approach and radical nephrectomy was 2% and 30%, respectively (p <0.001)., Conclusions: The kidney sparing approach rate in a community based health care system can approach rates at major academic centers. This practice pattern appears related to the addition of recent graduates and urological oncologists but also to a change in long-standing practice patterns of other community urologists. These data suggest that the use of kidney sparing approaches nationwide and the associated renal functional benefits may continue to increase., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Fibrin sealants have become increasingly popular in nearly all surgical specialties. The absorbable fibrin adhesive bandage (AFAB) is a novel, potentially revolutionary product made from dried fibrinogen and thrombin. The AFAB appears to have excellent efficacy in producing rapid hemostasis in a variety of experimental major renal trauma models. The AFAB also appears to enhance healing of the urinary collecting system. Further study is essential to explore new urologic applications of this exciting technology.

Purpose: In a porcine model we evaluated the efficacy of the absorbable fibrin adhesive bandage and other novel fibrin products for treating major renal stab wounds., Materials and Methods: In commercial swine we produced an almost lethal, grade 4 renal stab wound via a 3.5 cm. sagittal, centrally located, through-and-through laceration. Each pig then received treatment in random fashion, including conventional oversewing of capsular defects with absorbable gelatin sponge and horizontal mattress sutures in 6, external absorbable fibrin adhesive bandage that was pressure held for 60 seconds in 6, external and internal absorbable fibrin adhesive bandage that was applied externally, inserted into the renal defect and pressure held for 60 seconds in 6, liquid fibrin sealant that was placed in the laceration and held for 60 seconds in 8, fibrin foam that was applied in the same manner as liquid fibrin in 5 and closing of the peritoneum over the lacerated kidney without further treatment in 6. Blood loss and time to hemostasis were recorded. Animals were sacrificed at 6 weeks to evaluate the injured renal unit., Results: Compared with conventional therapy the absorbable fibrin adhesive bandage applied externally alone or externally and internally resulted in significantly less bleeding and significantly less time to hemostasis (p <0.001). Liquid fibrin and fibrin foam did not reliably achieve hemostasis. Postoperatively computerized tomography and histological sectioning suggested that the absorbable fibrin adhesive bandage results in a stable, durable clot and healing is at least as successful as with conventional treatment., Conclusions: The absorbable fibrin adhesive bandage appears to be a safe, rapid means of renal salvage after injury.

Purpose: We identified risk factors for complications of the lower extremities related to high lithotomy positioning during specific urethral reconstruction procedures in male patients., Materials and Methods: Records from 185 open urethroplasties were evaluated for position related complications of the lower extremities (the compartmental syndrome, rhabdomyolysis, neurapraxia). Morphometric data (patient height, weight) and surgical details (duration of surgery and lithotomy positioning, types of repair and stirrups, stricture length and location) were assessed., Results: In the 185 patients 18 position related complications (10%) were identified, 4 of which were severe. Univariate analysis showed length of stricture, and duration of surgery and lithotomy positioning to be statistically significant risk factors (p <0.05). Height, weight, body mass index and type of stirrups did not increase risk. Anterior end-to-end anastomosis and straightforward buccal mucosa patch grafts entailed negligible risk. Longer procedures (prostatomembranous and penile skin flap repairs) had higher complication rates (12% and 22%, respectively). Beginning penile skin flap procedures with patients in the supine position during flap harvesting followed by repositioning into high lithotomy for perineal flap transfer virtually eliminated the risk of severe complications., Conclusions: The risk of position related complications during urethral reconstruction is directly proportional to the duration of high lithotomy positioning. Procedures of less than 5 hours in duration had minimal risk. For complex flap procedures, we perform penile flap dissection with the patient supine and reposition for perineal flap transfer.

Purpose: Posterior urethral valves are usually detected during infancy by prenatal sonography. Rarely they may be diagnosed during later childhood, adolescence or even adulthood. Less is known about presentation and outcome in these older patients. We reviewed our experience at 4 institutions with the late presentation of posterior urethral valves., Materials and Methods: A 13-year retrospective review revealed the late presentation of posterior urethral valves in 47 patients 5 to 35 years old (mean age 8). Data collected included presenting symptomatology, radiographic findings and renal function. Statistical analysis determined the relationships among presenting symptoms, patient age at diagnosis and renal function., Results: The most common presenting symptoms were diurnal enuresis in 60% of the cases, urinary tract infection in 40% and voiding pain in 13%. Other presenting symptoms in less than 10% of the cases included poor stream, gross hematuria and proteinuria. At diagnosis hydronephrosis and vesicoureteral reflux were present in 40 and 33% of the patients, respectively, while serum creatinine was elevated in 35% and end stage renal disease had developed in 10%. The severity of presenting signs and symptoms was significantly associated with renal impairment, while patient age at diagnosis was not., Conclusions: Posterior urethral valves is not merely a disease of infancy. Voiding cystourethrography should be considered in boys older than 5 years who have voiding complaints, especially in association with diurnal enuresis or urinary tract infection. Patients who present late with posterior urethral valves are at risk for progression to end stage renal disease.