PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry.

BACKGROUND: Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. METHODS: African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. RESULTS: We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. CONCLUSIONS: African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.

Follow-up Management of Cystectomy Patients.

Bladder cancer is the sixth leading cancer in the United States. Radical cystectomy is a lifesaving procedure for bladder cancer with or without muscle invasion. Radical cystectomy is performed on 39% of these patients, and 35% will have a life-threatening recurrence. Distant metastases are the most common; local, upper tract, and urethral recurrence can also occur. Surveillance after cystectomy is critical to diagnosing recurrence early. Functional complications after urinary diversion include bowel dysfunction, vitamin B12 deficiency, acidosis, electrolyte abnormalities, osteopenia, nephrolithiasis, urinary tract infections, renal functional decline, and urinary obstruction, which can be reversed when diagnosed early.

Dentinal damage and fracture resistance of oval roots prepared with single-file systems using different kinematics.

INTRODUCTION: Vertical root fracture is a common finding in endodontically treated teeth, notably oval roots. The aim of the present study was to determine the effect of instrumentation kinematics and the material of instrument construction of single-file systems on dentin walls and fracture resistance of oval roots. METHODS: Sixty-five roots with oval canals were allocated into a control group (n = 5) and 3 experimental groups of 20 roots each. Group WO was instrumented with the WaveOne primary file (Dentsply Maillefer, Baillagues, Switzerland), group PT-Rec was prepared with F2 ProTaper files (Dentsply Maillefer, Baillagues, Switzerland) used in a reciprocating motion, and group PT-Rot was prepared with F2 ProTaper files used in a rotation motion. For crack evaluation, half of the samples (n = 30) were embedded in acrylic resin, and the blocks were sectioned at 3, 6, and 9 mm from the apex. The sections were examined under a stereomicroscope and scored for crack presence. The other half of the specimens (n = 30) were obturated using lateral condensation of gutta-percha and AdSeal sealer (Meta Biomed Co, Ltd, Chungbuk, Korea). The specimens were then subjected to a load of 1 mm/min to determine the force required to fracture the roots. RESULTS: WaveOne instruments induced the least amount of cracks and exhibited greatest resistance to fracture compared with ProTaper F2 files whether used in reciprocating or rotating motions. CONCLUSIONS: The alloy from which the material is manufactured is a more important factor determining the dentin damaging potential of single-file instruments than the motion of instrumentation.

Does initial learning curve compromise outcomes for robot-assisted radical cystectomy? A critical evaluation of the first 60 cases while establishing a robotics program.

BACKGROUND AND PURPOSE: Robot-assisted laparoscopic radical cystectomy (RARC) with pelvic lymph node dissection (PLND) has gained popularity as a minimally invasive alternative to open radical cystectomy (ORC) for the treatment of patients with bladder cancer. The learning curve (LC) for laparoscopic and robotic surgery can be steep. We aim to evaluate the effect of the initial LC on operative, postoperative, and pathologic outcomes of the first 60 RARC performed at our newly established robotics program. PATIENTS AND METHODS: After obtaining Institutional Review Board approval, we reviewed the clinical and pathologic data from 60 consecutive patients with clinically localized bladder cancer who underwent RARC with PLND from January 2008 to March 2010. The patients were grouped into tertiles and assessed for effect of LC using analysis of variance. RESULTS: Patient demographics and clinical characteristics were similar across tertiles. The mean total operative time trended down from the 1st to 3rd tertile from 525 minutes to 449 minutes, respectively (P=0.059). Mean estimated blood loss was unchanged across tertiles. Complications decreased as the LC progressed from 14 (70%) in the 1st tertile to 6 (30%) in each of the 2nd and 3rd tertiles (P<0.013). The mean total lymph node yield and number of positive margins were unchanged across tertiles. CONCLUSIONS: RARC with PLND can be performed safely at a high-volume newly established robotic surgery program with an experienced team without compromising operative, postoperative, and short-term pathologic outcomes during the LC for surgeons who are experienced in ORC.

Robotic radical cystectomy: where are we today, where will we be tomorrow?

While open radical cystectomy remains the gold-standard treatment for muscle-invasive bladder cancer and high-risk non-muscle invasive disease, robotic assisted radical cystectomy (RARC) has been gaining popularity over the past decade. The robotic approach has the potential advantages of less intraoperative blood loss, shorter hospital stay, less post-operative narcotic requirement, quicker return of bowel function, and earlier convalescence with an acceptable surgical learning curve for surgeons adept at robotic radical prostatectomy. While short to intermediate term oncologic results from several small RARC series are promising, bladder cancer remains a potentially lethal malignancy necessitating long-term follow-up. This article aims to review the currently published literature, important technical aspects of the operation, oncologic and functional outcomes, and the future direction of RARC.

Robotic distal ureterectomy with reimplantation in malignancy: technical nuances.

AIM: To present the point of technique of robotic distal ureterectomy under cystoscopic guidance with pelvic lymphadenectomy (PLND), ureteral reconstruction with and without a psoas hitch in patients with distal ureteral urothelial cancer (DUCC) and to review the current literature. METHODS: The various steps of operative technique of robotic PLND, distal ureterectomy under cystoscopic guidance, ureteral reconstruction with and without a psoas hitch in patients of DUCC are described. Several tricks have been highlighted to undertake such procedure. The published English literature was also searched using the key words; robot, laparoscopy, ureteral reimplantation, distal ureterectomy, psoas hitch, and ureteroneocystostomy; so as to provide an up to date review on subject. RESULTS: The technique robotic pelvic lymphadenectomy, distal ureterectomy, ureteral reimplantation with and without a psoas hitch in patients with DUCC was successful in both our patients. The mean operating room time, robotic (console) time, mean estimated blood loss and mean hospital stay were 250 min, 130 min, 150 cc and 2.2 days respectively. There were no complications. CONCLUSIONS: The technique of robotic distal ureterectomy with ureteral reimplant for malignant ureteral strictures continues to be in evolution. Surgeon should be versatile with various options and technical nuances while dealing with these cases. The short term oncologic outcomes appear to be satisfactory and encouraging, while the long term results are awaited.

Does peak systolic velocity correlate with renal artery stenosis in a pediatric renal transplant population?

PSV of renal transplant vessels, calculated during allograft ultrasonography, has previously been shown to correlate with TRAS. Controversy exists regarding the threshold PSV value (adult range: 1.5-3.0 ms), which should prompt further, more invasive investigations to confirm the diagnosis of TRAS. Furthermore, there is a paucity of literature regarding PSV values in the pediatric renal transplant population. In a group of pediatric renal transplant patients, we correlated post-operative renal transplant PSV values with BP, renal function (serum creatinine) and TRAS. All patients who underwent cadaveric or living-related renal transplantation at the HSC between 2001 and 2004 with at least 6 months of follow-up were reviewed through the HSC multi-organ transplant database. Post-operative allograft Doppler ultrasonography was performed during routine follow-up. PSV values obtained were correlated with BP and serum creatinine performed concomitantly. Finally, we correlated PSV in those patients who underwent more intensive investigations, including magnetic resonance and conventional angiography. Fifty-three patients underwent transplantation during the study period. Complete data available for 50/53 demonstrated a mean PSV of 2.13 m/s (range: 0.9-6.1 m/s) for all patients. Of six patients who underwent MRA for suspicion of TRAS, two (with mean PSV values of 1.93 m/s) were found to have clinically significant stenoses. Four of six without angiographic evidence of TRAS had mean PSV values of 2.22 m/s. Patients suspected of having TRAS demonstrated elevated median serum creatinine values compared with those without clinical suspicion of TRAS. However, both mean PSV and BP were not found to be statistically different in both patient subgroups. Furthermore, there was no correlation identified between PSV and serum creatinine and BP in these patient populations. Despite the utility of PSV for monitoring adult renal transplant patients, we did not find that PSV correlated with BP, nadir creatinine or identify those patients who, through subsequent investigations, were found to have TRAS in this pediatric population. Maintaining cognizance in conjunction with close clinical follow-up may identify patients at risk for this rare but potentially morbid complication of transplantation.

Potential adverse effect of sperm DNA damage on embryo quality after ICSI.

BACKGROUND: Sperm DNA damage is prevalent amongst infertile men and has been shown to strongly impact adversely natural reproduction, intrauterine insemination-assisted reproduction and to a lesser degree IVF/ICSI fertilization. The objective of this study was to examine further the relationship between sperm DNA denaturation (DD) and reproductive outcomes after ICSI. METHODS: We evaluated infertile couples (n = 60) undergoing IVF/ICSI at a single centre. Sperm DD was assessed by flow cytometry analysis of Acridine Orange-treated sperm and expressed as the percentage of sperm with DD. Couples were sub-grouped according to sperm DD results: group 1: 0-15%; group 2: >15-30%; group 3: >30%. RESULTS: There were no differences between the three groups with regard to maternal age, sperm parameters, oocyte maturation, fertilization or pregnancy rates. Group 3 had a significantly higher rate of multinucleation among the embryo cohorts compared to either groups 1 or 2 (20% versus 10% and 8% respectively, P = 0.04). There was a statistically insignificant trend toward an increased spontaneous pregnancy loss rate in group 3 (P =0.50). CONCLUSION: Although we did not observe significant relationships between sperm DNA damage and either fertilization or pregnancy rates, the potential adverse effect of sperm DNA damage on embryo quality and spontaneous pregnancy loss is concerning.