Reply by Authors We appreciate the comments on our study. There is clearly a road ahead and paths to tread to find the exact place of ultrasound SWE in the detection and phenotypic characterization of prostate cancer. There may be a place of combining this with MRI. However, publications in this area to date show promising results. What should be considered a discriminatory diagnostic cutoff level for benign and malignant lesions can be debated but there is some confidence that all studies in this area show differences in the relative stiffness estimates not only of cancer and noncancerous tissues but also of different Gleason grades (reference 12 in article).
Editorial Comment PCa detection remains a problem. Random TRUS biopsies have been the standard of care but they can often miss cancers and under grade the cancers that are identified. MRI has had success in identifying clinically significant PC and it may be helpful in active surveillance.1 SWE is a new technique that evaluates tissue stiffness.2 As most PCa is stiffer than normal prostate it can be detected by SWE and the stiffness appears to correlate with Gleason scores. However, benign prostatic nodules are also stiff, making evaluation of the central gland problematic with SWE.
Editorial Comment Imaging in localized prostate cancer is gaining importance. Specifically multiparametric MRI is frequently used for diagnosis, active surveillance, targeted biopsy and focal therapy. A major step in the acceptance and widespread use of MRI was the establishment of the standardized reporting system, PI-RADS® (Prostate Imaging-Reporting and Data System).1 Research on new techniques such as SWE should aim to establish comparable classification systems to catch up with MRI (reference 11 in article).
JU Forum The Journal of Urology® improves patient care by delivering to our readers the most current advances in the field, especially those with clinical implications and translation. Most often, this information is provided in the form of original scientific articles, review articles and guidelines. The Urological Survey section of The Journal broadens the focus to include pertinent papers published in other journals.
Editorial Comment In recent years there has been a dramatic increase in the number and availability of tools that assess risk following the diagnosis of PCa. These developments have occurred largely in 2 parallel tracks, including optimization of mpMRI, and discovery and validation of tissue based genomic tests (reference 4 in article).1 With little comparative study it has remained unclear whether these modalities are redundant or new prognostic value can be gleaned from additional testing (reference 17 in article).
Editorial Comment Genomic science has opened a new world of possibilities for understanding and treating men with prostate cancer. It enables for the first time ever the ability to directly assess the biological potential of the tumor in an individual and, thus, offers the promise of individualized treatment strategies based on biology rather than histology.
Editorial Comment This group examined a well characterized cohort of 183 patients who underwent IVC tumor thrombectomy and radical nephrectomy in a contemporary 10-year time frame at a highly experienced, high volume center. An important take home message is that symptomatic VTE develops postoperatively in a high fraction of patients, essentially more than 1 of 5, with VTE within 30 days after surgery in most of them. This is a much higher rate of VTE than has been observed for other complex genitourinary cancer surgeries, such as radical cystectomy.
Editorial Comment The incidence of VTE following major surgery is increased because of a pro-inflammatory hypercoagulable condition associated with anesthesia, surgical tissue manipulation and limited mobility during recovery. Cancer diagnosis also increases the risk of VTE and mortality is significantly higher in patients with cancer after a VTE diagnosis.1
Editorial Comment Among the many questions raised when prostate biopsy is to be MRI guided is what difference does it make if the MRI reveals more than 1 ROI? Patel et al help answer that question in the current study. It is not the number of ROIs but rather the degree of suspicion of any one of them, assessed in terms of the PI-RADS score, which portends the likelihood of serious cancer.
Editorial Comment The benefits of cytoreductive nephrectomy have been established based on the results of 2 prospective, randomized controlled trials that were done during the cytokine era (reference 2 in article).1 It is important to remember that most of the phase III trials which led to the approval of vascular endothelial growth factor receptor-tyrosine kinase inhibitors required initial CN prior to enrollment. Today initial CN continues to remain the recommended treatment in patients with mRCC in whom systemic therapy is anticipated (reference 1 in article).
Reply by Authors We agree with the comments. As noted, there is growing awareness about other important side effects of ADT, which may be less familiar to urologists. These side effects include liver disease as well as important effects on cognition and even mood disorders (reference 3 in article).
Editorial Comment Using SEER data with Medicare linkage Gild et al assembled a large study cohort from which they advance the persuasive argument that ADT is associated with significant risks to liver health. In the absence of a significant prospective study SEER with Medicare linkage likely represents the best data source to study this question in an American population.
Editorial Comment NAFLD is the most common cause of liver disease in Western countries. Gild et al analyzed SEER-Medicare linkage observational data to determine the association between primary ADT and the potential subsequent development of NAFLD in patients with prostate cancer. While acknowledging the known limitations of administrative data, using restricting criteria for the cohort to overcome potential comorbidities and treatment related confounders, and applying using propensity core adjustments, the authors found that ADT is associated with a greater risk of liver disease, particularly NAFLD.
This Month in Pediatric Urology Vesicoureteral reflux (VUR) is one of the original conditions (along with hypospadias, cryptorchidism and hydronephrosis) that helped define the field of pediatric urology. There were a variety of open surgical options for VUR and one of the earliest concerns was trying to determine where these procedures fit into possible treatments versus observation on antibiotic prophylaxis and spontaneous resolution. To help answer this question, the International Reflux Study (IRS) was conducted, and the IRS grading system was created and remains an internationally accepted standard today.
Erratum Volume 199, Number 5, Page 1202: Sentence 2 in Results in the Abstract should read: The 111 men treated with unilateral nerve sparing and the 75 treated with a nonnerve sparing procedure were grouped together.
Lower Urinary Tract Dysfunction and Associated Pons Volume in Wolfram Syndrome Wolfram syndrome (WFS) is a neurodegenerative disorder characterized by childhood-onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment and commonly bladder and bowel dysfunction. We hypothesize that there is an association between smaller pons, which contains the pontine micturition center, and abnormal lower urinary tract function.
Editorial Comment A complete response after multi-agent NAC is the target but it is achieved only a modest amount of the time (reference 2 in article). Negative transurethral bladder resection after NAC carries a high false-negative risk.1 Therefore, after NAC most patients should undergo consolidation with radical cystectomy or radiation.
The Role of Vitamin D Receptor Polymorphisms in Predicting Response to Therapy in Nonmuscle Invasive Bladder Carcinoma Although clinical and pathological predictors for bladder carcinoma recurrences and progression are relatively well defined, there is a paucity of genetic data and specifically, its association of SNPs in specific genes in predicting recurrence and progression following immunotherapy. The Vitamin D Receptor (VDR) gene has been found to regulate the immunomodulatory effects of Vitamin D and enhances the innate immunity system.We aim to look at three VDR Single Nucleotide Polymorphisms (SNP) and their predictive role on response to immunotherapy.
The Association of Aspirin Use with Survival Following Radical Cystectomy Aspirin may have antineoplastic properties through inhibition of inflammatory cytokines that regulate cell proliferation, angiogenesis and apoptosis. For patients with non-muscle invasive bladder cancer, aspirin use has been linked to a reduced risk of recurrence. Herein, we evaluated the association of aspirin with survival following radical cystectomy (RC).
Risk of Radiation from CT Urography in the Evaluation of Asymptomatic Microscopic Hematuria and Objectives: AUA guidelines for asymptomatic microscopic hematuria (AMH) recommend that patients undergo CT Urography (CTU), which is associated with high doses of ionizing radiation. The associated risk of secondary malignancy and mortality remain unknown. We herein model the risk of malignancy and associated mortality due to ionizing radiation from CTU relative to the additional diagnostic benefit offered over renal ultrasound.
Re: Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer D. E. Spratt, J. Zhang, M. Santiago-Jiménez, R. T. Dess, J. W. Davis, R. B. Den, A. P. Dicker, C. J. Kane, A. Pollack, R. Stoyanova, F. Abdollah, A. E. Ross, A. Cole, E. Uchio, J. M. Randall, H. Nguyen, S. G. Zhao, R. Mehra, A. G. Glass, L. L. C. Lam, J. Chelliserry, M. du Plessis, V. Choeurng, M. Aranes, T. Kolisnik, J. Margrave, J. Alter, J. Jordan, C. Buerki, K. Yousefi, Z. Haddad, E. Davicioni, E. J. Trabulsi, S. Loeb, A. Tewari, P. R. Carroll, S. Weinmann, E. M. Schaeffer, E. A. Klein, R. J.
Reply by Authors We agree with the points regarding the continued (and successful) role of conservative management, the use of hematoma diameter as a continuous variable and the need for a clinically relevant nomogram to enhance clinical decision-making. However, we disagree with the statement that ureteral stenting is “less relevant in relation to acute management of renal trauma.” Ureteral stenting represents a clinically relevant intervention for renal trauma, especially given that the AAST Organ Injury Scale specifies collecting system injury as an important factor stratifying renal trauma management.
Reply by Author There seems to be signaling that Rezūm therapy at 3-year followup has lower rates of surgical repeat treatment than some of the other minimally invasive therapies for benign prostatic hyperplasia. In addition, I agree that the definition of repeat treatment is narrow. Most patients would suggest that if they are still on a medication years after therapy, they are still on “treatment.” Ultimately the experience in the urological community, governed partly by safety and efficacy as well as reimbursement, will determine the long-term future of any minimally invasive therapy.
Re: Perinephric Hematoma Size is Independently Associated with the Need for Urological Intervention in Multisystem Blunt Renal Trauma This article is a timely and apt report on imaging specifics associated with urological interventions after renal trauma. As more renal injuries are managed nonoperatively, the importance of injury specifics beyond those captured by the AAST (American Association for the Surgery of Trauma) Organ Injury Scale becomes more apparent. Of 328 patients eligible for this study 194 (59%) had high grade renal injuries and only 7 (4%) underwent nephrectomy. This rate is low compared to a recent multi-institutional study showing a nephrectomy rate of 13% at level 1 United States trauma centers.
This Month in Adult Urology Large administrative databases increasingly are the source of information used in medical publishing. Inevitably, the reliability of the findings depends on the accuracy of the analyzed data. Errors in decimal point placement on recorded prostate specific antigen (PSA) values used in SEER (Surveillance, Epidemiology, and End Results) data called into question some studies in which PSA was an important variable. Similar issues with the VACCR (Veterans Affairs Central Cancer Registry) are reported by Guo et al (page 000) from Stanford, California.
Editorial Comment This article identifies errors in PSA values in the VACCR, a massive national cancer registry, compared to the gold standard of the medical record values. The PSA value in more than 25% of patients was found to be misclassified when using registry data alone.
Reply by Authors Many researchers have highlighted that contemporary management of VUR should always be risk adapted and individualized based on the history of pyelonephritis and subsequent renal parenchymal damage, presence of bladder and bowel dysfunction, and parental preference.1,2 Although 30.5% of the patients in our series required more than 1 endoscopic treatment, only 10.4% had the need for a third injection to cure their high grade VUR. In fact, our resolution rate of 69.5% after a single injection of Dx/HA suggests that it makes sense to give a child with grade IV or V reflux at least 1 chance at endoscopic treatment before considering more invasive procedures.
Editorial Comment Surgical correction is often considered in children with persistent high grade VUR, renal parenchymal scarring and/or recurrent febrile urinary tract infections. Secondary to its minimally invasive nature, the frequency of endoscopic injection using Dx/HA increased rapidly in the early 2000s, with a subsequent decline in more recent years paralleling an overall decrease in VUR diagnosis and antireflux surgery.1,2 The literature in aggregate suggests that endoscopic injection is a relatively effective treatment for most VUR, while emphasizing the impact of grade and structural/functional bladder anomalies on ultimate success rates.
Reply by Authors Flank positioning has the potential to improve outcomes and decrease complications not only in patients with obesity and pulmonary compromise, but also in a subgroup of patients with certain anomalies who are at higher risk for visceral injury. Mobility of the kidney during tract dilatation, although rare, is a drawback associated with the flank position. Renal mobility may result in short dilatation and failure to enter the calyceal system. Using a bi-prong forceps to dissect and dilate the tract under direct endoscopic vision as well as telescopic dilatation are salvage techniques to overcome kidney mobility.
Reply by Authors We agree with the comments that capturing patient reported HRQOL is paramount in BC research and care. We believe that the BUSS is unique because in 10 questions it explores the most vital issues to patients and is written in language appropriate for anyone with the disease. Thinking beyond pelvic toxicity, we created the BUSS as a holistic measure, focusing on global HRQOL.
Editorial Comment Oncology patients are confronted with physical and psychological consequences from the disease and treatment, which ultimately have a significant impact on overall HRQOL. In recent years PROs have increasingly had integral roles in clinical trials, quality of care assessment and comparative effectiveness research. Accurately assessing HRQOL in patients with BC is challenging due to the disparate courses and treatments in such patients (ie transurethral resection, intravesical therapy, cystectomy, chemotherapy and radiation therapy).
Editorial Comment The consequences of radical orchiectomy in a young man are substantial, including psychological distress,1 reduced fertility and an increased risk of testicular failure.2 If the testis could be preserved in the 5% to 10% cases of benign lesions which present as a testicular mass, these consequences may be avoided. Unfortunately it is not yet possible to accurately diagnose benign masses preoperatively.
Editorial Comment Once again Germany is leading voice in the field of testis sparing surgery for small lesions. This group formulated guidelines to help treat patients with small lesions that have a relatively high chance of being benign.
Editorial Comment This study is important as many have placed their faith in MRI to avoid unnecessary prostate biopsies. Perhaps it was misplaced? Further, increasingly we are learning that MRI is significantly operator dependent, adding yet another variable to the use of this technology to avoid biopsy. So how do we incorporate the results of the PROMIS trial (reference 8 in article) and this study, which are really from centers of experience, if not excellence?
Reply by Authors The comments adequately indicate the scenario. Currently many patients may require TEOMG, particularly patients who refuse mouth graft harvesting, patients with a congenitally small mouth, ie the Chinese population,1 patients with a small mouth opening due to previous trauma or surgery in the mandibular arch, patients requiring large bilateral graft harvesting, which represents a significant predictor of patient dissatisfaction (reference 24 in article), patients requiring large rectangular graft harvesting for 2-stage urethroplasty and patients with recurrent urethral stricture who have already undergone graft harvesting form each cheek.
Editorial Comment Anterior urethral strictures present a reconstructive challenge. Various techniques have been developed to improve the chances of long-term urethral patency, including oral mucosa grafts. Although harvesting buccal mucosa is an expedient technique which is cost-effective and done easily by reconstructive urologists, it is not a perfect solution and complications can arise.
Editorial Comment For nontraumatic and longer strictures of the anterior urethra the role of genital skin flaps has decreased slowly in the last 20 years. Flaps are now reserved for complex and post-radiation strictures.1 Today oral mucosal grafts have gained popularity as the material of choice for augmentation in most cases.
Prenatal Hydronephrosis: Another Swing of the Pendulum? Without question the recognition of prenatal hydronephrosis as a diagnostic tool has revolutionized pediatric urology and been of great benefit to our patients. However, one must also acknowledge that the diagnosis comes with significant burdens. Beyond the considerable economic costs there is the anxiety experienced by expectant parents and the physical toll of numerous imaging studies inflicted on these infants and young children. Finding the right balance between not wanting to miss a significant anatomical obstruction and limiting excessive testing and intervention has been a constant challenge with moving goalposts and evolving guidelines.
Editorial Comment Routine monitoring of PROs in cancer has been associated with decreased emergency room visits as well as improved HRQOL, patient-physician communication and even overall survival in patients with metastatic cancer.1 In bladder cancer PRO use may be limited by the variety of disease states, various PRO instruments and perhaps most importantly by time.
Reply by Authors It is true that we grouped together all patients who underwent radical cystectomy due to bladder cancer regardless of their history. However, this approach resembles a real-life setting and thus is translatable to other urology departments. More importantly, patients with bladder cancer and ureteral stenting were compared not only to those with nephrostomy tube insertion, but also to the majority with no drainage at all. The proportion of patients with pTa/pTis/pT1 disease was similar between the no drainage group (23%) and the ureteral stent group (28%), and the same was true for history of intravesical instillations (21% vs 25%).
This Month in Pediatric Urology The increasing use of ultrasound in children, especially serial longitudinal imaging for hydronephrosis, has resulted in identification of more renal cysts in children. Many of these cystic lesions are seen in asymptomatic children, indicating a clear need for guidelines to help determine whether additional evaluation with computerized tomography (CT) is necessary and to define followup protocols for low risk cystic lesions. There have been few studies comparing radiographic and pathological findings to confirm the validity of the Bosniak classification for evaluating renal cysts in children.
This Month in Adult Urology Magnetic resonance imaging (MRI) fusion guided prostate biopsy is being used increasingly for the diagnosis of prostate cancer but important questions remain. Is a negative MRI study sufficient to exclude high risk disease without a biopsy? Can a template biopsy be eliminated and targeted biopsy alone be performed? Two studies in this issue of The Journal compare MRI directed transrectal prostate biopsy with perineal template biopsies. Mortezavi et al (page 000) from Switzerland found that 19.9% of clinically significant cancers would have been missed if only 3 targeted fusion biopsy samples were performed compared to a perineal template.
Re: Stenting Prior to Cystectomy is an Independent Risk Factor for Upper Urinary Tract Recurrence The authors report that in patients undergoing radical cystectomy preoperative drainage of the collecting system with ureteral stenting may be associated with an increased risk of upper tract recurrence when compared to nephrostomy. Upper tract drainage for hydronephrosis was performed in 114 of the 1,005 patients in this study (11%), including 53 (46%) by ureteral stenting and 61 (54%) by percutaneous nephrostomy. Recurrence was observed in 7 patients (13%) with stents, 24 patients (3%) with no drainage and no patient with a nephrostomy.
Evaluation of an Aggressive Prostate Biopsy Strategy in Men Younger than 50 years of Age Longitudinal cohort studies and guidelines demonstrate that PSA ≥1 ng/mL in younger patients confer an increased risk of delayed prostate cancer (PC) death. In our institution we have used an aggressive biopsy strategy among younger patients with PSA of>1 ng/ml. Our objective was to determine the proportion of detected cancer and specifically, clinical significant cancer, with this strategy.
Reply by Authors The comments highlight the importance of this work and the need for additional confirmatory trials. Although our initial pilot study suggests an improvement in infectious complications in patients who received SIM (reference 22 in article), a larger study is needed to confirm these results. Accordingly a multicenter trial run through the SWOG (Southwest Oncology Group) known as S1600 or SIMmune (A Randomized Phase III Double-Blind Clinical Trial Evaluating the Effect of Immune-Enhancing Nutrition on Radical Cystectomy Outcomes) is set to launch in 2018.
Editorial Comment Despite decades of practice there has been minimal improvement in the morbidity of RC. Importantly a strong association exists between complications and nutritional status but there is limited evidence to guide urologists on the choice and effectiveness of nutritional interventions. The current study demonstrates that an immune enhanced formula may attenuate the inflammatory response in patients who undergo RC, suggesting the potential for supplementation to improve RC outcomes. However, the small sample size limits the ability to determine whether supplementation translates into a clinically relevant benefit such as decreased complications.
Editorial Comment The dissemination and implementation of evidence-based medicine across specialties is an ongoing challenge. That challenge is particularly evident in the field of perioperative nutrition. In 2011 Drover et al reported a systematic review of 35 randomized controlled trials of arginine supplemented immunonutrition in surgical patients, which identified a “substantial reduction in infection and shorter length of hospital stay.”1 Those studies were predominantly on gastrointestinal surgery and they included no urological studies.
Erratum Volume 199, Number 4, Page 954, Abstract: In sentence 1 in Material and Methods, the number of positive cores is 2 or fewer and the percentage of core involvement is 50% or less.
Editorial Comment The authors analyze use of serial ultrasound and diuretic renography when following patients with unilateral SFU grade 3 to 4 hydronephrosis. The issue at hand is predicting which hydronephrotic kidneys have obstruction that may threaten development or function. The authors present a cautionary tale, concluding that 13.3% to 14.1% of kidneys with stable or decreased hydronephrosis on ultrasound demonstrate worsening function on diuretic renography. While this finding should give pause to the pediatric urologist who relies solely on ultrasound when following children with hydronephrosis, no easy solution is afforded.
Editorial Comment The fate of the pediatric kidney exhibiting severe UTD is a concern for the pediatric urologist, the assumption being that the condition may be associated with a deleterious process that could affect renal function. The authors of this carefully designed study set out to determine if the changes observed through time on US correlate with functional findings on diuretic renography. The results of the study imply that they do not.
Editorial Comment Ryan et al present the results of a single arm study of in nmCRPC using abiraterone plus prednisone. PSA responses were excellent but time to PSA progression was not as impressive as I would have anticipated, given that patients had lower PSA levels and less advanced disease than in mCRPC trials (reference 2 in article). Were these results due to the reduced dose of prednisone? In these patients at high risk is nmCRPC more aggressive than in patients with slowly progressing mCRPC?
Editorial Comment The IMAAGEN trial investigators report data on treating a prospective cohort of men with nonmetastatic, castration resistant prostate cancer with abiraterone plus prednisone using a reduced dose of prednisone 5 mg daily. This dose change may seem trivial but using prednisone with abiraterone is important for toxicity reduction. Abiraterone depletes testosterone by inhibiting CYP17 conversion of androgen precursors to testosterone. However, these precursors are shunted into alternative enzymatic pathways.
Editorial Comment The authors present a case series of cystic renal masses in children, for which correlation between imaging and histology was available. They show rather elegantly that pediatric urologists should be worried about any lesion with solid components (ie Bosniak 3 or 4) and can perhaps safely observe the majority of those without solid components (Bosniak 1 or 2). Furthermore, their data seem to lend support to the modified Bosniak classification based on Doppler ultrasound suggested by Wallis et al (reference 5 in article), which can in turn lead to avoiding radiation is many children being assessed and followed for a cystic renal lesion.
Editorial Comment The authors report a single institution experience of renal cysts, correlating radiographic findings with pathology. They found that cysts with radiographic findings consistent with Bosniak 3 or 4 classification are more likely to have malignancy. As they note, this study does not mark the first time that pathological findings and radiological characteristics of the Bosniak classification, validated in adults, have been correlated in children. However, the prior study (reference 5 in article) had only 5 patients with radiology plus pathology results, and thus this latest series is substantially larger.
Editorial Comment OS has been a topic of great interest in the study of varicocele associated infertility in the last 2 decades. Studies have confirmed the association of sperm DNA damage with OS and mitochondrial inactivity (reference 17 in article).1 In this quest sperm mitochondrial proteomic studies provide insight into the structural and functional irregularities which in turn may explain the apparent sperm dysfunction.
Editorial Comment The authors have contributed to improve quality registration of care in men with localized prostate cancer by selecting a set of pertinent quality indicators from the literature, which is an essential first step in this process.
Validation of PI-RADS version 2 for the detection of prostate cancer The second version of the Prostate Imaging Reporting and Data System (PI-RADSv2) was introduced in 2015 to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging (mpMRI). Recently, low cancer detection rates (CDR) for PI-RADSv2 category 4 lesions were reported. Therefore the aim of the study was to evaluate the CDR of PI-RADSv2 in a large prospective cohort.
Menopause and Risk of Kidney Stones Metabolic changes due to menopause may alter urine composition and kidney stone risk but results from prior work on this association have been mixed. We examined menopause and risk of incident kidney stones and changes in 24-hour urine composition in the Nurses’ Health Study II.
Family history is under-estimated in children with isolated hypospadias: a French multicenter report of 88 families. Whereas familial forms of complex disorders/differences of sex development have been widely reported, data regarding isolated hypospadias are sparse and a family history is thought to be less frequent. We aimed 1-to determine the frequency of hypospadias in families of hypospadiac boys 2-to determine if theses familial forms exhibit a particular phenotype 3-to evaluate the prevalence of genetic defects of the main candidate genes.A prospective inclusion of 395 hypospadiac boys screened for family history with a standardized questionnaire, extensive clinical description, family tree and sequencing of AR, SF1, SRD5A2 and MAMLD1 was performed.
Reply by Authors The comment is correct. While our large administrative data set strongly suggests that neither specific surgeon experience nor mesh itself appears to be the cause of adverse outcomes after mesh based vaginal POP surgery, it does not include the granular details to accurately predict who will and who will not have long-term surgical success with or without mesh. However, the growing presence of “precision medicine,” ie tailoring medical decisions and treatments to an individual patient rather than to the population at large, is at hand.
Editorial Comment The saying, “hindsight is 20/20,” is an appropriate one in the setting of POP surgery. If the outcomes were known beforehand, the surgeon would be reassured that the correct procedure had been elected in the correct patient. Complications could be averted and outcomes optimized.
Reply by Authors We agree with the comment that there is a growing body of literature to support active surveillance in patients with cystic renal masses, including recent AUA (American Urological Association) (reference 20 in article) and CUA (Canadian Urological Association) (reference 4 in article) management guidelines. Our data demonstrated similar findings that patients with unifocal cystic renal cell carcinoma evaluated using a radiological threshold of greater than 50% cystic have an excellent prognosis on active surveillance on short-term followup.
Editorial Comment This study by Kashan et al adds to the growing body of literature suggesting that cystic renal cell carcinoma typically behaves in indolent fashion and has a favorable prognosis with or without surgical resection. Although most resected cystic lesions were found to be malignant, most patients had favorable pathology and no patient experience recurrence or metastatic disease during followup.
Reply by Authors The comment points out the rationale for choosing greater than 50% cystic on imaging as the cutoff of our exclusion criteria. Although this may seem arbitrary, we chose to evaluate only enhancing cystic renal masses that were greater than 50% cystic on computerized tomography in our study based on 2 reasons. 1) A recent study noted that at least a 45% cystic component on imaging was an independent prognostic factor for favorable survival (reference 3 in article). 2) It is a simple approach that can be easily performed by radiologists and applied to a clinical routine.
Editorial Comment The authors present outcomes in a subset of 138 pathologically identified cystic renal masses with a 50% or greater cystic component on preoperative imaging. Approximately three-fourths of these lesions proved to be malignant at resection. Most of these lesions were low grade and low stage, and none had metastasized by the 5-year followup. Aspects inherent to the Bosniak classification system (presence/size of solid component) proved prognostic in terms of malignant potential as did male gender.
Editorial Comment Does androgen deprivation therapy increase the risk of impaired cognition or Alzheimer disease in men with prostate cancer? Two large studies suggest that the risk is not increased.1,2 But other studies have shown an increased risk of Alzheimer disease and impaired cognition.3 Marzouk et al found no impact of androgen deprivation therapy on self-reported cognitive function in men with localized prostate cancer.
Reply by Authors We agree with the comment that we cannot ignore the increasing rate of sepsis after transrectal biopsy and the alarming rise of antimicrobial resistance which is causing it. However, although multiparametric magnetic resonance imaging of the prostate may enable us to decrease the number of unnecessary prostate biopsies that are performed, we still need to prevent sepsis in patients who require prostate biopsies because multiparametric magnetic resonance imaging reveals suspicious lesions.
Editorial Comment As antibiotic stewardship is increasingly emphasized, Jiang et al address the important question of whether alternative strategies to curb post-transrectal prostate biopsy infections effective. They present evidence that targeted prophylaxis based on rectal swab cultures is equivalent to nontargeted prophylaxis to prevent post-biopsy sepsis. Notably the nontargeted group included patients receiving single agent and multi-agent augmented prophylaxis, and the group with multi-agent augmented prophylaxis had the lowest rate of sepsis overall (0.29% vs 0.56% in the targeted group).
Editorial Comment Mortezavi et al provide an important contribution in this study evaluating the accuracy of mpMRI and FTB compared to a TTSPB reference standard. All 415 men underwent mpMRI and TTSPB. The 291 men (70%) with abnormal MRI also underwent FTB. This study nicely complements PROMIS (Prostate MRI Imaging Study) by evaluating MRI and FTB instead of conventional TRUS biopsy (reference 7 in article).
Editorial Comment In this clinically relevant study the authors assessed the diagnostic accuracy of mpMRI and FTB compared to TTSPB in a cohort of 415 consecutive patients.
Reply by Authors One of the acknowledged limitations of the current study is the lack of available data on the patient chief complaint. We and others have previously reported that most patients can identify a primary bothersome complaint that motivates them to seek physician care (reference 22 in article). Because these previous studies used the AUA-SI, they were limited by the fact that this questionnaire does not address urinary incontinence. The LURN observational cohort study did not capture the motivating complaint or bother related to urinary incontinence.
Editorial Comment Helfand et al present data on urinary incontinence on 477 men taking part in the LURN study. Post-void dribbling occurred in 41% of the men with 29% reporting urge urinary incontinence. Overall 51% subjects reported urinary incontinence. Erectile dysfunction, depression and anxiety scores were also associated with urinary incontinence. Significant predictors of urinary incontinence were age, race, sleep apnea and clinical site. This important study demonstrates a higher than expected incidence of male incontinence.
Editorial Comment The authors report a randomized, phase II induction trial of 4 vs 10 months of a gonadotrophin-releasing hormone receptor antagonist in men treated with intermittent therapy. There were no significant differences in the stated outcomes between the 2 induction times.
Editorial Comment Most large population analyses of muscle invasive bladder cancer confirm the gender trend encountered by urologists in practice. While the majority of those with muscle invasive bladder cancer are male, females tend to have worse cancer outcomes. Muscle invasive bladder cancer is not considered a gender dimorphic malignancy but the consistently increased mortality and the higher recurrence rate in females suggest that our current paradigms for diagnosis and treatment with a gender ambivalent approach should continue to be examined.
Editorial Comment The subject of gender specific outcomes in medicine in general and specifically in urological oncology has medical, policy making and social implications. It has not been investigated as rigorously as other issues. When using cancer and outcome as key words in PubMed®, one receives just over 250,000 items. However, adding gender specific lowers the number of results to 117. This underscores the fact that female patients are underrepresented in modern biomedical research. The past literature suggested disparities in health care, carcinogen exposure, genetics, hormone balance and social life as the possible mechanisms of worse outcomes in female patients with urothelial cancer.
Editorial Comment With this exhaustive and well designed meta-analysis Uhlig et al have cemented the finding that bladder cancer is deadlier for women than men. The authors highlighted the biological bases of these differences, including different carcinogenic effects of tobacco in women and the possible impact of estrogen on bladder cancer outcomes. However, each proposed mechanism has limited supporting evidence.
Editorial Comment Despite using the 2 new variables flank position and ultrasound access the authors claim good results during PNL. However, the clearance data are based on suboptimal postoperative imaging. It would be proper to look at this study from each aspect (flank position and ultrasound access) separately.
Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer Androgen deprivation therapy is associated with the development of diabetes and metabolic syndrome. To our knowledge its effect on the development of nonalcoholic fatty liver disease, a condition which frequently co-occurs with metabolic syndrome and other subsequent liver conditions such as liver cirrhosis, hepatic necrosis or any liver disease, has not been investigated.
The Value of a Urology Consult In this issue of The Journal of Urology®, Kurtzman et al (page 180) report a reduced risk of emergency department (ED) revisits and computerized tomography (CT) exposure for children seen by a urologist at their index presentation.1 This study raises many thought-provoking questions regarding delivery-of-care models for urological disease. Using the South Carolina Medical Encounter data, a robust administrative claims data set, the authors evaluated ED care patterns for first time pediatric stone formers.
This Month in Pediatric Urology This month we have 2 studies for which large pools of aggregated data were used. One article concerns pediatric urinary stones. Nephrolithiasis is a growing area of concern and may soon join hypospadias, vesicoureteral reflux, cryptorchidism and hydronephrosis as a leading common pediatric urology problem. The other article examines the status of bladder management and continence in the adult with spina bifida using data from the National Spina Bifida Patient Registry from 2009 to 2015.
Reply by Authors Despite tremendous improvements in the design of penile implants as well as the surgical techniques used to deploy them, infections invariably develop in a small percent of patients. The urologist is then faced with the decision to remove the device in its entirety or salvage it.
Editorial Comment The age-old dictum of explanting an infected penile prosthesis has been challenged in the last 2 decades by the seminal work of Mulcahy.1 Historically the infected penile prosthesis was removed and a second surgery, usually 6 to 12 weeks later, was required to implant a new penile prosthesis. Often the penis was shortened as a result of the fibrosis induced by prosthesis removal.
Reply by Authors The ability of MRI to detect aggressive PCa is fundamental to defining its role in routine diagnostic practice. We agree with the comments that in addition to Gleason score, IDC/CR findings have emerged as clinically relevant histopathological parameters of prognostic significance (reference 11 in article). We found increased biopsy detection of IDC/CR positive PCa in targeted lesions visualized on MRI compared with concurrent sampling of MRI negative regions of the prostate. Admittedly this did not comprise a 12-core systematic biopsy but we point out that most patients with IDC/CR underwent standard systematic biopsy before imaging, which was negative for tumor or demonstrated low grade, IDC/CR negative disease only.
Editorial Comment In this study Prendeville et al found that adding MRI-TBx to the prostate cancer diagnostic pathway improved detection of the IDC/CR pattern. It is important to recognize that the authors compared MRI-TBx against SMN-Bx rather than 12-core systematic biopsy, which is more typical of MRI fusion biopsy studies and standard clinical practice. Based on the biopsy scheme sextant biopsy was not given an equal opportunity to sample regions of the prostate containing MRI lesions. Moreover, a concurrent 12-core systematic biopsy may detect additional cancers missed by MRI-TBx due to targeting or registration error.
Editorial Comment Cribriform morphology can be present in Gleason grade 4 tumors as well as in intraductal carcinoma of the prostate. As these entities are considered high risk, it is now recommended that cribriform morphology be reported in biopsy pathology reports.1 The authors present a valuable perspective on the superior ability of MRI to detect cribriform histological patterns on targeted biopsy over standard biopsy. This contrasts with previous literature suggesting that cribriform Gleason pattern 4 tumors may be less visible on MRI (reference 23 in article).
Editorial Comment Followup imaging after PCNL should be obtained to assess for residual stone fragments and silent obstruction. There is also evidence that immediate postoperative imaging with CT may reduce readmissions due to missed complications (reference 28 in article). However, in the absence of clinical guidelines to recommend imaging type(s), frequency and interval it is not surprising that there is variation in imaging practices across the country.
This Month in Adult Urology Sleep disorders correlate with nocturia in men. Whether a similar association with daytime lower urinary tract symptoms exists is less well studied. In this multicenter evaluation of the NHANES (National Health and Nutrition Examination Survey) database Fantus et al (page 161) identified 3,071 men who had completed the sleep, prostate and kidney questionnaires.1 The 8.8% of men who reported a sleep disorder had a significantly higher body mass index, higher incidence of diabetes and greater comorbidity.
Predatory Publishing in Pediatric Urology In academic publishing predatory open access publishing is an exploitative business model that involves charging fees to authors without providing the editorial and publishing services associated with traditional journals (open access or not). Predatory publishing has become the buzzword in the last few years, as it permeates across the majority of medical and surgical subspecialties.
Reply by Authors The comment emphasizes some important points. We agree that the most desirable biomarker would be able to identify not only viable disease but also teratoma after chemotherapy. miRNAs may not meet this ideal definition but we must recall that in current clinical practice we have no biomarkers and only a handful of clinical predictive tools with known limitations. We believe that our suggested paradigm offers some improvement on this relative vacuum.
Editorial Comment Leão et al detail the ability of 3 serum miRNAs to predict residual viable GCT after chemotherapy in patients with nonseminomatous tumors treated with undergoing post-chemotherapy retroperitoneal lymph node dissection. A promising result with miR-371a-3p yielded an AUC of 0.87 with 100% sensitivity for residual masses less than 3 cm to predict viable GCT. However, as the authors correctly highlight, the predictive ability of miRNAs fell short for teratoma by incorrectly classifying 44% of teratomas less than 3 cm.
Editorial Comment An understanding of bladder management and continence among adults with spina bifida is currently lacking. In this article the authors describe the outcomes of 1,372 adults with spina bifida who participate in the National Spina Bifida Patient Registry. They compare the results between adults with MMC and nonMMC spina bifida, and between the adults and the 3,878 children in the registry. They found that urinary continence and use of clean intermittent catheterization increase with age. Not surprisingly, patients with nonMMC spina bifida are more continent than those with MMC.
Editorial Comment Whether vasectomy causes prostate cancer has been debated for 30 years. To date studies have primarily compared the prostate cancer incidence between men who underwent vasectomy and various control groups (reference 12 in article). Randall et al approached this topic differently, examining whether vasectomy reversal is associated with a reduced prostate cancer risk among men who have undergone vasectomy. According to the criteria of causality of Hill, if vasectomy truly causes prostate cancer, vasectomy reversal should theoretically decrease this risk.
Are Electronic and Paper Questionnaires Equivalent to Assess Patients with Overactive Bladder? Overactive bladder syndrome is defined as urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence in the absence of urinary tract infection or another obvious pathological condition. Electronic questionnaires have been used in a few specialties with the hope of improving treatment outcomes and patient satisfaction. However, they have not been widely used in the urological field. When treating overactive bladder, the main outcome is to improve patient quality of life.
Reply by Authors We appreciate the comments highlighting the importance of the impact of policy on the end user, the patient. Empirical evidence is critical to design an optimized and more egalitarian health care system. As mentioned our findings may add to the body of literature separating health insurance coverage from access to health care (reference 18 in article). Given the previous null effects of prostate cancer care coordination programs in vulnerable populations, it is best not to prematurely exalt care navigation as a panacea for health disparities but rather to carefully consider the contribution of each component of IMPACT (patient education, financial and social support) on the health of beneficiaries.
Editorial Comment The ACA has expanded insurance coverage to approximately 30 million Americans through insurance subsidies and expanded Medicaid eligibility.1 While it is often assumed that comprehensive insurance equates to unrestricted access to necessary health care services, a growing body of empirical evidence suggests that this is simply not the case. Alcalá et al recently found that compared to individuals with employer sponsored health insurance those with Medicaid and exchange insurance products were significantly less likely to be able to see a primary care physician or a specialist in California.
Editorial Comment Policies that impact population health often have unintended consequences for individuals. Nabhani et al found that compared with men who stayed in the encompassing, high touch IMPACT program men with prostate cancer who transitioned to insurance under the ACA from IMPACT had worse physical quality of life but no significant difference in mental health and prostate cancer specific quality of life.
Reply by Authors We agree that a simple reading system for prostatic MRI that can be used internationally in a standardized fashion is required. PI-RADS has achieved the first important step toward standardization on an international level. However, interreader variability when using the current PI-RADS version 2 is an issue, as observed in the literature. This finding may be due to subjectivity when reading the images, differences in protocols and/or scanner variations, experience level of the reading physician or sample errors of the different targeted biopsy methods.
Reply by Authors Retrospective observational data present challenges in terms of measurement and confounding factors. The aim of our study was to analyze practice patterns around imaging in children with blunt renal trauma to inform practices in the era of the ALARA (as low as reasonably achievable) principle. The lack of indications for repeat CT in our study is an important limitation. However, as stated in the results section, 54% of repeat scans were performed with delayed imaging. Additionally in the multivariable model we controlled for confounding factors that could lead to repeat scans unrelated to the urinary tract, such as whether the patient had multiple internal organs injured or underwent exploratory laparotomy.
Reply by Authors While being able to accurately predict volitional voiding after traumatic SCI is noteworthy, much remains to be accomplished. With an annual incidence of 17,000 new traumatic spinal cord injuries per year in the United States the fact that only 30% of patients recover the ability to void volitionally means that more than 12,000 persons annually sustain permanent genitourinary dysfunction following injury. As a result, continued efforts to recapitulate bladder function remain necessary in the more than 200,000 men and women nationally who cannot void following traumatic SCI.
Editorial Comment One of the most important questions patients ask shortly after SCI is, “Will I void again?” The authors used a large, well characterized data set of 4,327 patients with 1-year followup data from the United States NSCID (reference 14 in article) to answer this question. This work builds on the work of Pavese et al using lower extremity motor function to predict urinary continence and bladder emptying after 1 year (reference 13 in article). That work used a smaller data set of 1,250 patients with far fewer patients (111) available for external validation from the EMSCI.
Editorial Comment Acknowledging the limitations of administrative data sets and the inability to demonstrate causality, this study still highlights several important aspects of acute care for children with nephrolithiasis. First, many children will initially present to nonpediatric hospitals, representing an opportunity and need for engaging adult urology and ED colleagues in the care of these children. In addition, although rates of urological consultation were low, urology consult was associated with decreased rates of ED revisits and use of CT.
Reply by Authors We agree that a onetime screening effort designed as in this study is less likely to yield a reduction in prostate cancer specific mortality. Indeed, the Swedish arm of the ERSPC demonstrated a significant survival benefit in the intervention arm (reference 15 in article). It is also correct that this study is relatively small in comparison, although the control group included about 25,000 men or about a quarter the the size of the entire ERSPC.
Editorial Comment Large-scale randomized, controlled trials have unequivocally demonstrated that PSA screening reduces prostate cancer mortality.1,2 Lundgren et al report a contrasting finding from a screening trial begun in Stockholm in 1988. A total of 2,400 men 55 to 70 years old were invited to undergo onetime screening including PSA, digital rectal examination and transrectal ultrasound with quadrant biopsy if PSA was greater than 10 ng/ml. In the next 20 years prostate cancer mortality in this cohort was no different than in an age matched control group (RR 1.05, 95% CI 0.83–1.27).
Re: Risk Stratification of Equivocal Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate We read this article with great interest and propose further adjustments to the current PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 scoring to improve the discriminatory power of multiparametric magnetic resonance imaging (MRI). The authors conclude that PI-RADS score 3 lesions should be considered for followup rather than being considered equivocal. However, there are some fundamental concerns regarding the management of PI-RADS score 3 lesions.
Re: Missed Opportunities to Decrease Radiation Exposure in Children with Renal Trauma The authors performed a local retrospective review of the use of computerized tomography (CT) in the setting of pediatric renal trauma. They report that patients with high grade (3 or greater) renal trauma who did not undergo delayed imaging on the initial CT were more likely to undergo repeat CT. The central conclusion of the article is that failure to perform delayed imaging on initial CT may miss an opportunity to decrease radiation exposure. The authors recommend “obtaining delayed imaging on the initial CT in all stable pediatric patients with high grade (3 to 5) renal trauma” on the premise that this practice will decrease radiation exposure overall.
Is It Safe to Reduce Water Intake in the Overactive Bladder Population? A Systematic Review Overactive bladder imposes a significant socioeconomic burden on the health care system. It is a commonly held belief that increased fluid intake (8 glasses of water per day) is beneficial for health. However, increased fluid intake exacerbates overactive bladder symptoms. Thus, it is imperative that clinicians appropriately educate patients for whom increased water intake may be detrimental (women with overactive bladder), in contrast to patients with comorbidities that necessitate increased water intake (nephrolithiasis).
When Clinical Trials Disagree In clinical and public health research randomized trials are indispensable for learning about what works. Trials can avoid many known biases of observational studies and provide a seemingly simple recipe for inference, ie if outcomes differ significantly between groups, the intervention works. However, trials have well-known limitations. Results may not generalize to other populations or other time horizons. Also, perplexingly, trials of similar interventions may yield conflicting results. Unfortunately, in these situations there is no universally accepted recipe for making sense of the evidence.
Serum miRNA Predicts Viable Disease after Chemotherapy in Patients with Testicular Nonseminoma Germ Cell Tumor Retroperitoneal lymph node dissection is recommended for residual masses greater than 1 cm after chemotherapy of nonseminomatous germ cell tumors. Currently there is no reliable predictor of post-chemotherapy retroperitoneal lymph node dissection histology. Up to 50% of patients harbor necrosis/fibrosis only so that a potentially morbid surgery has limited therapeutic value. In this study we evaluated the ability of defined serum miRNAs to predict residual viable nonseminomatous germ cell tumors after chemotherapy.
FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical Trials: Future Direction for Research For 3 decades the 1988 NIDDK (National Institutes of Diabetes and Digestive and Kidney Diseases) criteria for the research definition of interstitial cystitis (IC) has not only driven the design and outcomes for clinical trials, but also shaped the definition of the clinical condition.1 In the last 4 decades only 2 interventions, intravesical dimethyl sulfoxide (RIMSO-50) and pentosan polysulfate sodium (Elmiron), have been approved (1978 and 1996, respectively) for the treatment of IC. On December 7, 2017 the FDA (U.S.
National Imaging Trends after Percutaneous Nephrolithotomy Followup imaging after percutaneous nephrolithotomy serves to detect postoperative complications, residual fragments and silent hydronephrosis. However, the timing and optimal imaging modality remain poorly defined. We describe imaging use patterns after percutaneous nephrolithotomy.
Addressing Financial Toxicity: The Role of the Urologist As improvements in medical technology continue, the costs of cancer care and number of cancer survivors will continue to increase. As a result, the prevalence of financial toxicity, or the financial hardships patients face during treatment, will also escalate. The impact of financial toxicity on patients with cancer and their families is concerning, and adverse consequences include worse patient well-being, medication adherence, out-of-pocket expenses and clinical outcomes.1 Although the problem has been identified, durable solutions are lacking.
Editorial Comment This is an interesting article addressing a not too uncommon scenario in which a patient on required antiplatelet therapy is in need of surgical resection of a suspicious renal mass. While it makes complete sense intuitively that patients on clopidogrel can potentially have more bleeding complications, only 8 patients were on continued clopidogrel therapy. Therefore, some observations have to be viewed with caution. For example, the fact that those patients who remained on clopidogrel had longer operative times could be an incidental finding unless the operative notes dictated state that the increased operative time was due to intraoperative bleeding.
WITHDRAWN: Re: Managing a Pessary Business This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at (http://www.elsevier.com/locate/withdrawalpolicy).
Re: Loss of the Urothelial Differentiation Marker FOXA1 is Associated with High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer.
Information for Authors The Journal of Urology® contains 3 sections: Adult Urology, Pediatric Urology and Urological Survey. Original clinical and translational research studies will be considered for publication in the Adult and Pediatric Urology Sections. Translational research manuscripts must have a clear and proximate translation to patient care, and only preclinical scientific studies that have the direct potential to translate into new and improved standards of care will be reviewed.
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