Radiation exposure associated with computed tomography for pediatric urolithiasis evaluation: A scoping review of the literature.

INTRODUCTION: Computed tomography (CT) imaging is used for assessment of pediatric urolithiasis in cases where ultrasound is inconclusive. The utility of CT imaging must be considered alongside the potential risks of radiation exposure in this patient population due to the increased risk of cancer development. The purpose of this review is to investigate the radiation exposure associated with standard-dose and low-dose computed tomography (CT) imaging for the assessment of pediatric urolithiasis. METHODS: A scoping literature review over a 23 year period between 2000 and 2023 was conducted of all English-language studies reporting on the use of non-contrast CT imaging for assessment of pediatric urolithiasis. Patients that were specified as pediatric with age ≤20 years at time of intervention and undergoing standard-dose or low/ultra-low-dose CT were included. Low-dose and ultra-low-dose CT were defined as a radiation dose ≤3.0 mSv and ≤1.9 mSv, respectively. RESULTS: A total of 8121 articles were identified and after screening, 6 articles representing 309 patients were included in this scoping review. Of the articles reviewed, standard non-contrast CT radiation doses for pediatric urolithiasis evaluation ranged from 2.9 to 5.5 mSv and low-dose CT radiation dose was reported to be 1.0-2.72 mSv. Only 2 studies directly evaluated low-dose CT imaging compared to standard-dose CT imaging for pediatric urolithiasis assessment. Radiation reduction approaches did not negatively impact urolithiasis detection or characterization in 2 studies reviewed. CONCLUSIONS: CT radiation doses for suspected or known pediatric urolithiasis are underreported and vary greatly with underutilization of low-dose/ultra-dose protocols for pediatric urolithiasis especially in comparison to the adult population. Results from this scoping review support that low-dose CTprotocols for pediatric stone disease are feasible to reduce radiation exposure.

A quantitative analysis of voiding cystourethrogram features confirms the association between high-grade vesicoureteral reflux with male sex, younger age, and hydronephrosis.

INTRODUCTION: Vesicoureteral reflux (VUR) is commonly diagnosed in the workup of urinary tract infections or hydronephrosis in children. Traditionally, VUR severity is graded subjectively based on voiding cystourethrogram (VCUG) imaging. Herein, we characterized the association between age, sex, and indication for VCUG, by employing standardized quantitative features. METHODS: We included renal units with a high certainty in VUR grade (>80% consensus) from the qVUR model validation study at our institution between 2013 and 2019. We abstracted the following variables: age, sex, laterality, indication for VCUG, and qVUR parameters (tortuosity, ureter widths on VCUG). High-grade VUR was defined as grade 4 or 5 The association between each variable and VUR grade was assessed. RESULTS: A total of 443 patients (523 renal units) were included, consisting of a 48:52 male/female ratio. The median age at VCUG was 13 months. Younger age at VCUG (<6 months) was associated with greater odds of severe VUR (odds ratio [OR] 2.0), and there was a weak correlation between age and VUR grade (ρ=-0.17). Male sex was associated with increased odds of high-grade VUR (OR 2.7). VCUGs indicated for hydronephrosis were associated with high-grade VUR (OR 4.1) compared to those indicated for UTI only. Ureter tortuosity and width were significantly associated with each clinical variable and VUR severity. CONCLUSIONS: Male sex, younger age (<6 months), and history of hydronephrosis are associated with both high-grade VUR and standardized quantitative measures, including greater ureter tortuosity and increased ureteral width. This lends support to quantitative assessment to improve reliability in VUR grading.

Diagnosis, Classification, and Contemporary Management of Undescended Testicles.

This article provides a comprehensive review regarding undescended testicles and other related conditions. We have included background information summarizing variable clinical presentations, epidemiology, and the implications of undescended testis (UDT) on fertility and malignancy risk. This article has an emphasis on the approach to diagnosis and surgical management for the UDT. The purpose of this review is to provide readers with useful clinical tools for assessing and treating patients with cryptorchidism.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Multi-institutional Validation of Improved Vesicoureteral Reflux Assessment With Simple and Machine Learning Approaches.

PURPOSE: Vesicoureteral reflux grading from voiding cystourethrograms is highly subjective with low reliability. We aimed to demonstrate improved reliability for vesicoureteral reflux grading with simple and machine learning approaches using ureteral tortuosity and dilatation on voiding cystourethrograms. MATERIALS AND METHODS: Voiding cystourethrograms were collected from our institution for training and 5 external data sets for validation. Each voiding cystourethrogram was graded by 5-7 raters to determine a consensus vesicoureteral reflux grade label and inter- and intra-rater reliability was assessed. Each voiding cystourethrogram was assessed for 4 features: ureteral tortuosity, proximal, distal, and maximum ureteral dilatation. The labels were then assigned to the combination of the 4 features. A machine learning-based model, qVUR, was trained to predict vesicoureteral reflux grade from these features and model performance was assessed by AUROC (area under the receiver-operator-characteristic). RESULTS: A total of 1,492 kidneys and ureters were collected from voiding cystourethrograms resulting in a total of 8,230 independent gradings. The internal inter-rater reliability for vesicoureteral reflux grading was 0.44 with a median percent agreement of 0.71 and low intra-rater reliability. Higher values for each feature were associated with higher vesicoureteral reflux grade. qVUR performed with an accuracy of 0.62 (AUROC=0.84) with stable performance across all external data sets. The model improved vesicoureteral reflux grade reliability by 3.6-fold compared to traditional grading (P < .001). CONCLUSIONS: In a large pediatric population from multiple institutions, we show that machine learning-based assessment for vesicoureteral reflux improves reliability compared to current grading methods. qVUR is generalizable and robust with similar accuracy to clinicians but the added prognostic value of quantitative measures warrants further study.

Concurrent Multicystic Dysplastic Kidney, Posterior Urethral Valves, and Obstructive Ureterocele in a Male Pediatric Patient: A Case Report.

Congenital anomalies of the kidney and urinary tract (CAKUT) are diagnosed in approximately 3-6 per 1000 live births and represent a spectrum of urologic conditions impacting the kidneys, ureter, bladder, and urethra.1 Although both are considered under the classification of CAKUT, there is no known unifying pathophysiologic mechanism for ureteroceles and posterior urethral valves with only 1 case report noted in the literature. Herein we report the only documented case of a patient with CAKUT related to posterior urethral valves, ureterocele, and multicystic dysplastic kidney.

Attaining competency and proficiency in open pyeloplasty: a learning curve configuration using cumulative sum analysis.

INTRODUCTION: The learning curves for minimally invasive pyeloplasty techniques have been described in the past. However, the learning curve in achieving competency in open pyeloplasty has not been described. Hence, we aim to evaluate a single surgeon series of open pyeloplasty technique using the cumulative sum (CUSUM) methodology. METHODS: We retrospectively reviewed all open pyeloplasties performed by a single surgeon (AJL) between January 2008 and March 2020. Collected variables included: sex, age at surgery, operative time, hospital stay, pre-operative ultrasound, pre-operative nuclear scans, pre-operative anteroposterior diameter, associated anomalies, laterality (left or right), type of stent, pre-operative split renal function, and duration of follow-up. A CUSUM analysis was used: the highest peak, plateau and downward trends for complications (defined as Clavien-Dindo classification ≥ 3b) were identified on the plot and set as the transition points between five phases (learning, competency, proficiency, case-mix, and mastery). RESULTS: Based on the CUSUM analysis, the index surgeon reached the competency phase after performing their 13th open pyeloplasty and became proficient after the 70th case. In the case-mix phase (104th-126th cases), where the surgeon may be performing more complex cases while increasing trainee involvement, there was a slight increase in complication rates. After the 126th case, the surgeon entered the mastery phase, where there was consistent decreasing trend in complications. CONCLUSIONS: Surgeons performing open pyeloplasty in children following completion of their surgical training will continue to learn through their early cases until achieving competency. Technical competency may be reached after the 13th case. In this report, we looked at the number of cases to become proficient in open pyeloplasty procedure in children. A surgeon may achieve technical proficiency in the procedure after their 13th case.

Omental Procedures During Peritoneal Dialysis Insertion: A Systematic Review and Meta-Analysis.

OBJECTIVES: Peritoneal dialysis (PD) is an option for ultrafiltration for patients with end-stage renal disease. Once placed, PD catheters may malfunction often due to omental wrapping. Omental procedures such as omentectomy and omentopexy may reduce this risk. This investigation aims to perform a systematic review and meta-analysis of the literature on the role of omental procedures on PD catheter insertions. METHODS: Following protocol registration on PROSPERO (CRD42020218950), a systematic review was performed in accordance with the Cochrane Collaboration. A literature search was performed in February 2021 across Medline, EMBASE, Scopus, and Cochrane Library. Records with patients who underwent PD catheter insertion with and without omental manipulation were included. The records underwent screening, full-text review, and data extraction. Study qualities were assessed using RoBINS-I and RoB2. Effect estimates were extracted as risk ratios and corresponding 95% confidence intervals (CI) were pooled using inverse variance method with random-effect model. RESULTS: Of 510 records identified, 15 studies were included in the meta-analysis (1 RCT, 2 prospective, 12 retrospective). With omental procedures, there was decreased the likelihood of failure requiring removal of PD catheter (RR 0.47, 95% CI 0.38, 0.58) and PD catheter obstruction (RR 0.23, 95% CI 0.14, 0.39); there was no difference in likelihood of catheter malposition or migration (RR 0.87, 95% CI 0.23, 3.29) or peritonitis (RR 0.74, 95% CI 0.40, 1.35). CONCLUSION: Based on the current low to moderate quality of evidence, omental manipulation at the time of PD catheter insertion confers benefits of decreased obstruction and failure requiring removal.

Vascular hitch for paediatric pelvi-ureteric junction obstruction with crossing vessels: institutional analysis and systematic review with meta-analysis.

OBJECTIVE: To compare the outcomes for laparoscopic vascular hitch (VH) and dismembered pyeloplasty in patients with pelvi-ureteric junction obstruction (PUJO) secondary to crossing vessels (CV). PATIENTS AND METHODS: Patients who underwent laparoscopic management of CV at our institution were identified between 2008 and 2020. Baseline characteristics and outcome measures were compared between those who underwent VH and those who underwent dismembered pyeloplasty. Those who underwent VH were selected intraoperatively by identifying CV in the absence of intrinsic obstruction by assessing resolution of hydronephrosis after cranially displacing the CV away from the PUJ, followed by intraoperative fluid bolus and diuretic test. In addition, a systematic search and meta-analysis were performed in June 2020 (International Prospective Register of Systematic Reviews [PROSPERO] ID CRD42020195833). RESULTS: A total of 20 patients underwent VH and 74 dismembered pyeloplasty. On multivariate analysis, VH was associated with: shorter operative time (P = 0.001; odds ratio [OR] 0.455, 95% confidence interval [CI] 0.294-0.705) and length of stay (P = 0.012; OR 0.383, 95% CI 0.183-0.803), lower use of stents (P < 0.001; OR 0.024, 95% CI 0.004-0.141) and opioid administration (P = 0.005; OR 0.157, 95% CI 0.044-0.567). From our literature search, 194 records were identified and 18 records were included (three comparative and 16 non-comparative). Meta-analysis of the comparative studies and our institutional data showed similar success rates (relative risk [RR] 1.77, 95% CI 0.33-9.52) and complication rates (RR 0.75, 95% CI 0.20-2.82). VH was associated with shorter operative time (standardised mean difference [SMD] -1.65, 95% CI -2.58 to -0.72 h) and hospital stay (SMD -1.41, 95% CI -2.36 to -0.47 days). The VH success rates ranged from 87.5% to 100% in the identified studies. Failure of VH was associated with unrecognised concomitant intrinsic obstruction in addition to CV. CONCLUSIONS: A VH, for well-selected patients with CV without concomitant intrinsic obstruction, offers a high success rate with shorter operative times.

Posterior Urethral Valves Outcomes Prediction (PUVOP): a machine learning tool to predict clinically relevant outcomes in boys with posterior urethral valves.

BACKGROUND: Early kidney and anatomic features may be predictive of future progression and need for additional procedures in patients with posterior urethral valve (PUV). The objective of this study was to use machine learning (ML) to predict clinically relevant outcomes in these patients. METHODS: Patients diagnosed with PUV with kidney function measurements at our institution between 2000 and 2020 were included. Pertinent clinical measures were abstracted, including estimated glomerular filtration rate (eGFR) at each visit, initial vesicoureteral reflux grade, and renal dysplasia at presentation. ML models were developed to predict clinically relevant outcomes: progression in CKD stage, initiation of kidney replacement therapy (KRT), and need for clean-intermittent catheterization (CIC). Model performance was assessed by concordance index (c-index) and the model was externally validated. RESULTS: A total of 103 patients were included with a median follow-up of 5.7 years. Of these patients, 26 (25%) had CKD progression, 18 (17%) required KRT, and 32 (31%) were prescribed CIC. Additionally, 22 patients were included for external validation. The ML model predicted CKD progression (c-index = 0.77; external C-index = 0.78), KRT (c-index = 0.95; external C-index = 0.89) and indicated CIC (c-index = 0.70; external C-index = 0.64), and all performed better than Cox proportional-hazards regression. The models have been packaged into a simple easy-to-use tool, available at https://share.streamlit.io/jcckwong/puvop/main/app.py CONCLUSION: ML-based approaches for predicting clinically relevant outcomes in PUV are feasible. Further validation is warranted, but this implementable model can act as a decision-making aid. A higher resolution version of the Graphical abstract is available as Supplementary information.

A machine learning-based approach for quantitative grading of vesicoureteral reflux from voiding cystourethrograms: Methods and proof of concept.

INTRODUCTION: The objectivity of vesicoureteral reflux (VUR) grading has come into question for low inter-rater reliability. Using quantitative image features to aid in VUR grading may make it more consistent. OBJECTIVE: To develop a novel quantitative approach to the assignment of VUR from voiding cystourethrograms (VCUG) alone. STUDY DESIGN: An online dataset of VCUGs was abstracted and individual renal units were graded as low-grade (I-III) or high-grade (IV-V). We developed an image analysis and machine learning workflow to automatically calculate and normalize the ureteropelvic junction (UPJ) width, ureterovesical junction (UVJ) width, maximum ureter width, and tortuosity of the ureter based on three simple user annotations. A random forest classifier was trained to distinguish between low-vs high-grade VUR. An external validation cohort was generated from the institutional imaging repository. Discriminative capability was quantified using receiver-operating-characteristic and precision-recall curve analysis. We used Shapley Additive exPlanations to interpret the model's predictions. RESULTS: 41 renal units were abstracted from an online dataset, and 44 renal units were collected from the institutional imaging repository. Significant differences observed in UVJ width, UPJ width, maximum ureter width, and tortuosity between low- and high-grade VUR. A random-forest classifier performed favourably with an accuracy of 0.83, AUROC of 0.90 and AUPRC of 0.89 on leave-one-out cross-validation, and accuracy of 0.84, AUROC of 0.88 and AUPRC of 0.89 on external validation. Tortuosity had the highest feature importance, followed by maximum ureter width, UVJ width, and UPJ width. We deployed this tool as a web-application, qVUR (quantitative VUR), where users are able to upload any VCUG for automated grading using the model generated here (https://akhondker.shinyapps.io/qVUR/). DISCUSSION: This study provides the first step towards creating an automated and more objective standard for determining the significance of VUR features. Our findings suggest that tortuosity and ureter dilatation are predictors of high-grade VUR. Moreover, this proof-of-concept model was deployed in a simple-to-use web application. CONCLUSION: Grading of VUR using quantitative metrics is possible, even in non-standardized datasets of VCUG. Machine learning methods can be applied to objectively grade VUR in the future.

Personalized application of machine learning algorithms to identify pediatric patients at risk for recurrent ureteropelvic junction obstruction after dismembered pyeloplasty.

PURPOSE: To develop a model that predicts whether a child will develop a recurrent obstruction after pyeloplasty, determine their survival risk score, and expected time to re-intervention using machine learning (ML). METHODS: We reviewed patients undergoing pyeloplasty from 2008 to 2020 at our institution, including all children and adolescents younger than 18 years. We developed a two-stage machine learning model from 34 clinical fields, which included patient characteristics, ultrasound findings, and anatomical variation. We fit and trained with a logistic lasso model for binary cure model and subsequent survival model. Feature importance on the model was determined with post-selection inference. Performance metrics included area under the receiver-operating-characteristic (AUROC), concordance, and leave-one-out cross validation. RESULTS: A total of 543 patients were identified, with a median preoperative and postoperative anteroposterior diameter of 23 and 10 mm, respectively. 39 of 232 patients included in the survival model required re-intervention. The cure and survival models performed well with a leave-one-out cross validation AUROC and concordance of 0.86 and 0.78, respectively. Post-selective inference showed that larger anteroposterior diameter at the second post-op follow-up, and anatomical variation in the form of concurrent anomalies were significant model features predicting negative outcomes. The model can be used at https://sickkidsurology.shinyapps.io/PyeloplastyReOpRisk/ . CONCLUSION: Our ML-based model performed well in predicting the risk of and time to re-intervention after pyeloplasty. The implementation of this ML-based approach is novel in pediatric urology and will likely help achieve personalized risk stratification for patients undergoing pyeloplasty. Further real-world validation is warranted.

Evolving trends in peri-operative management of pediatric ureteropelvic junction obstruction: working towards quicker recovery and day surgery pyeloplasty.

OBJECTIVE: To describe the evolution of practice patterns for pediatric pyeloplasty and determine how these changes have impacted length of stay (LOS), reoperation rates and return emergency department (ER) visits. METHODS: We reviewed our pyeloplasty database from 2008 to 2020 at a quaternary pediatric referral center and we included children 0-18 years undergoing pyeloplasty. Variables captured included: age, sex, baseline and follow-up anteroposterior diameter (APD) and differential renal function (DRF). We also collected data on the use of drains, catheters and/or stents, nausea and vomiting prophylaxis, opioids, regional anesthesia, and non-opioid analgesia. Outcomes were LOS, reoperation rates and ER visits. RESULTS: A total of 554 patients (565 kidneys) were included. Reoperation rate was 7%, redo rate 4% and ER visits 17%. There was a trend towards less opioids, indwelling catheters and internal stents and increasing non-opioid analgesia, externalized stents, and regional anesthesia during the study period. Same-day discharge (SDD) was possible for 88 (16%) children with no differences in reoperation or readmission rates between SDD and admitted (ADM). There was a difference in ER visits (21 [24%] vs. 26 [6%]; p = 0.04) for SDD vs. ADM, respectively. On multivariate analysis, the only predictor of ER visits was younger age. Patients < 7 months were more likely to present to ER (15/41; 37% vs. 6/47, 13%; p = 0.009). Multivariate analysis determined indwelling catheters and opioids were associated with ADM while dexamethasone and ketorolac with SDD. CONCLUSION: Progressive changes in care have contributed to a shorter LOS and increasing rates of SDD for pyeloplasty patients. SDD appears to be feasible and does not result in higher complication rates. These data support the development of a pediatric pyeloplasty ERAS protocol to maximize quicker recovery and foster SDD as a goal.

Spermatogenesis in pre-pubertal boys with Leydig cell neoplasms suggests paracrine stimulation by testosterone.

INTRODUCTION: Pediatric Leydig cell tumors (LCTs) represent approximately 4% of pre-pubertal testicular tumors and are known to cause precocious puberty secondary to testosterone production. While gonadotropins and testosterone are known to initiate spermatogenesis beginning in puberty, it is yet to be determined if a similar phenomenon is triggered by isolated testosterone production in prepubescent boys. OBJECTIVE: To determine if testicular pathology in pre-pubertal pediatric patients with LCTs exhibit spermatogenesis secondary to paracrine testosterone stimulation. STUDY DESIGN: We reviewed patients who underwent orchiectomy for a testicular tumor from 2003-17. We included patients with LCTs and compared them to children with non-LCT pathology (teratomas and epidermoid cysts). We excluded other pathologies and tumors in pubertal patients. Data were collected on the presence of spermatogenesis on pathology, tumor markers and serum hormone results. RESULTS: Orchiectomy for testicular tumors were completed in 66 patients, of which 20 were included in the non-LCT group and 9 in the LCT group. Two of the 9 LCT patients had bilateral pathology. Age at presentation was 6.3 ± 5.8 years for the non-LCT group vs. 8.4 ± 1.6 years for LCTs (p = 0.261). Spermatogenesis was detected in 7 (64%) LCT specimens vs 2 (10%) non-LCT specimens (p = 0.002). Age of the spermatogenesis patients in the non-LCT group (11.08 ± 2.5 years) was older than LCT ones (8.3 ± 2.0 years), suggesting that spermatogenesis in the non-LCT group may be due to early pubertal development. The summary figure demonstrates spermatogenesis identified in a pre-pubertal LCT patient. DISCUSSION: In this study, pre-pubertal males with LCTs were identified to have pathology evidence of spermatogenesis compared to controls with non-LCT pathology. This represents the first study assessing paracrine testosterone effects on spermatogenesis in pre-pubertal patients with LCTs. In contrast, adult literature on LCTs primarily report on resulting concerns for fertility, gynecomastia and testicular atrophy. CONCLUSION: LCTs can induce spermatogenesis in prepubertal patients. This reinforces the hypothesis that paracrine testosterone signaling plays a role in spermatogenesis. Our findings could help explore novel fertility preservation opportunities in children.

Vascular inflow after renal transplantation: Does the arteriotomy technique impact early allograft perfusion and function?

BACKGROUND: There are two main techniques for arterial reconstruction in RT: TA using a stab longitudinal incision which creates an elliptical opening and AP which fashions a circular defect. We hypothesized that AP creates a natural anastomosis lumen, similar to the donor renal artery, which optimizes RT perfusion. METHODS: A retrospective review of a single-institution database was performed between 2000 and 2018. Twenty patients who underwent AP arteriotomy were compared to 40 TA-matched controls. Data were collected on creatinine (preoperative, nadir, and time to nadir), and DUS RI and PSV at 1 week, 3 months, and 6-12 months post-RT. RESULTS: ttNC was shorter in the AP group (5 ± 4 vs 12 ± 13 days; P = .03). PSV at 1 week was lower in the AP group (186 ± 65 cm/s vs 232 ± 89 cm/s; P = .04). There was no difference in nadir creatinine value (P = .26), preoperative creatinine (P = .66), and initial postoperative creatinine (P = .80). RI at week 1 were not different between groups (P = .37). Follow-up DUS showed the difference in PSV between groups became non-significant (1 month P = .50 and 6-12 months P = .53). CONCLUSIONS: AP arteriotomy in RT improves early perfusion and function parameters (ttNC and initial PSV) as compared to TA. AP arteriotomy optimizes early allograft reperfusion, which may have important long-term implications and deserves further evaluation.

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer.

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill-defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.

Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer.

Selected patients with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) detected on transrectal ultrasound (TRUS)-guided biopsies may be considered for active surveillance (AS); however, a proportion of these will harbor more aggressive disease. The purpose of this study was to determine if morphologies of Gleason pattern 4 PCa may predict upgrading and/or upstaging after radical prostatectomy (RP). A database search for men with GS 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy that underwent RP between January 2010 and October 2015 identified 152 patients. Two blinded genitourinary pathologists independently reviewed the biopsies and assessed ill-defined glands (IDG), fused glands, small or large cribriform patterns, and glomerulations. Patient age, serum prostate-specific antigen (PSA), percentage (%) of biopsy sites involved by 3 + 4 = 7 PCa, and overall extent of pattern 4 were also recorded. GS and stage (presence or absence of extraprostatic extension [EPE]) were retrieved from RP reports. Data were compared using independent t tests and chi-square. Inter-observer agreement was calculated using Cohen's Kappa statistic. Percent of biopsy sites and extent of pattern 4 were compared to statistically significant morphologies using the Spearman correlation. 28.3 % (43/152) of patients were upgraded to GS >3 + 4 = 7 at RP (GS 4 + 3 = 7 [N = 17], GS 4 + 3 = 7 with tertiary pattern 5 [N = 25], and GS 4 + 5 = 9 [N = 1]) and 44.1 % (67/152) showed EPE after RP. PSA was associated with both upgrading (8.5 ± 5.4 vs. 6.9 ± 3.2 ng/mL, [p = 0.04]) and EPE (8.2 ± 4.6 vs. 6.7 ± 3.2 ng/mL, [p = 0.03]). IDG, fused glands, and glomerulations were not associated with upgrading or EPE (p > 0.05) with moderate to strong inter-observer agreement (K = 0.76-0.88). There was strong inter-observer agreement for small and large cribriform formations (K = 0.93 and 0.94, respectively) and both patterns were strongly associated with upgrading (p < 0.001) and EPE (p = 0.02) on RP. Strong associations were observed between increasing number of morphologies and both upgrading (p = 0.0.25) and EPE (p < 0.001). Overall extent of pattern 4 was associated with upgrading (p = 0.009) and EPE (p = 0.019) while percent of sites involved by GS 3 + 4 = 7 was only associated with EPE (p = 0.023). Cribriform morphology correlated to percentage of sites with 3 + 4 and overall extent of pattern 4 (rho = 0.25, p = 0.002, rho = 0.20, p = 0.015, respectively). Presence of cribriform morphology on TRUS-guided biopsy is strongly associated with upgrading and upstaging at RP and shows near-perfect inter-observer agreement whereas IDG, fused glands, and glomerulations were not useful. Cribriform morphology may be of importance when considering treatment plans for patients with intermediate risk PCa.

Suture slippage in knotless suture anchors resulting in subacromial-subdeltoid bursitis.

Rotator cuff repair using a suture bridge and knotless suture anchors is a relatively new, but increasingly used technique. The suture bridge technique creates an anatomically similar and more secure rotator cuff repair compared with conventional arthroscopic techniques and the use of knotless anchors eliminates the challenges associated with knot tying during arthroscopic surgery. However, previous in vitro biomechanical tests have shown that the hold of the suture in a knotless suture anchor is far lower than the pullout strength of the anchor from bone. Up until now slippage has been a theoretical concern. We present a prospectively diagnosed case of in vivo suture loosening after rotator cuff repair using a knotless bridge technique resulting in subacromial-subdeltoid bursitis.

Prostatic ductal adenocarcinoma: An aggressive variant that is underdiagnosed and undersampled on transrectal ultrasound (TRUS)-guided needle biopsy.

INTRODUCTION: We sought to determine if prostatic ductal adenocarcinoma is undersampled and/or underdiagnosed at transrectal ultrasound (TRUS)-guided biopsy. METHODS: With institutional review board approval, we searched our pathology database between 2008 and 2014 for patients with a diagnosis of ≥10% ductal adenocarcinoma on radical prostatectomy and available TRUS-guided needle biopsy specimens. Three blinded genitourinary pathologists independently examined the biopsy slides. The presence or absence of ductal adenocarcinoma was determined. Diagnostic accuracy was calculated using consensus diagnosis as the reference standard. Inter-observer agreement was assessed using Cohen's kappa coefficient. RESULTS: Based on consensus review, 66.7% (12/18) biopsy specimens demonstrated ductal adenocarcinoma and 33.3% (6/18) demonstrated conventional acinar prostatic adenocarcinoma. The sensitivity/specificity for each reader (R) was: 83/100% (R1), 100/83% (R2) and 58/83% (R3) and the inter-observer agreement was only fair (K=0.32). Only two of the original needle-biopsy reports correctly identified ductal adenocarcinoma (sensitivity = 17%). The main limitations of the study are the relatively small sample size and the potential for selection bias since we could only examine patients who underwent radical prostatectomy. CONCLUSIONS: Prostatic ductal adenocarcinoma may be undersampled at TRUS-guided biopsy and in this study was under-reported in routine clinical practice. This highlights the importance of increased awareness of ductal adeoncarcinoma and the need for clear diagnostic criteria. These findings have significant clinical impact especially when determining candidacy for active surveillance protocols.

Cribriform morphology predicts upstaging after radical prostatectomy in patients with Gleason score 3 + 4 = 7 prostate cancer at transrectal ultrasound (TRUS)-guided needle biopsy.

Selected patients with transrectal ultrasound (TRUS)-guided biopsies containing Gleason score 3 + 4 = 7 prostate cancer (PCa) may be considered candidates for active surveillance (AS). The purpose of this study was to determine if there are features that predict PCa upstaging and/or upgrading after radical prostatectomy (RP) in patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsies. We searched our institution's database for patients with Gleason score 3 + 4 = 7 PCa diagnosed on TRUS-guided biopsy who underwent subsequent RP between January 2010 and January 2015. Two blinded genitourinary pathologists independently reviewed and assessed the following on biopsies: (a) nuclear size, nucleolar size and distribution of macronucleoli of PCa, which were subjectively graded using a semi-quantitative scale from 1 to 3, and (b) PCa with cribriform morphology and the size of cribriform disease. Patient age, serum prostate-specific antigen (PSA) and PSA density (PSAD) were also recorded. The Gleason score and stage (presence or absence of organ-confined disease (OCD)) were retrieved from RP reports. Comparisons were performed between groups using the chi-square test and Spearman correlation. One hundred and four patients were identified to have met inclusion criteria. The mean age was 63 (±6.1) years. Mean PSA and PSAD at diagnosis were 7.5 (±4.2) and 0.25 (±0.15) ng/mL, respectively. Gleason scores were upgraded to greater than 3 + 4 = 7 in 26.9 % (28/104) of patients, and 44.2 % (46/104) of patients had no OCD after RP. There was no correlation between age, PSA, PSAD or percent of biopsies with Gleason pattern 4 for either Gleason score upgrading or absence of OCD at the time of RP (p > 0.05). Thirty patients had cribriform morphology on TRUS-guided biopsy of which 60 % (18/30) had no OCD at RP (p = 0.04) while 36.7 % (11/30) were upgraded to Gleason score ≥3 + 4 = 7 after RP (p = 0.15). There was no association between nuclear size, nucleolar size and/or distribution of macronucleoli with upgrading and/or absence of OCD (p > 0.05). The size of cribriform pattern was not associated with the absence of OCD (p = 0.43) or Gleason score upgrade (p = 0.28). A proportion of patients with Gleason score 3 + 4 = 7 PCa at needle biopsy do not have OCD or are upgraded to higher Gleason scores after RP. In our study, patients with Gleason score 3 + 4 = 7 PCa with the presence of cribriform pattern 4 had a significantly increased chance of being found to have no OCD at the time of RP. There were no clinical or pathologic parameters at the time of TRUS-guided biopsy that identified risk factors for Gleason score upgrading at RP in this study. Cribriform morphology detected on biopsy in patients with Gleason score 3 + 4 = 7 PCa is associated with tumour upstaging after RP and may be considered a contraindication to active surveillance.