Among Active Surveillance Candidates Does Obesity Influence Tumor Aggressiveness and/or Location? The CDC (Centers for Disease Control and Prevention) estimates that more than a third of Americans are obese. In regard to prostate cancer (PC), obesity is linked to more aggressive cancers and increased PC mortality but a decreased risk of low grade PC.1 Indeed, at nearly every stage of disease obesity makes a more aggressive cancer. Obesity increases the risk of recurrence after surgery and radiation, and even increases the risk of castrate resistant PC after androgen deprivation therapy.1 The lone exception appears to be among men with metastatic castrate resistant PC.
Reply by Authors The newer alternative approaches to treatment for congenital urological malformation need to be critically assessed and evaluated as recommended by the IDEAL group for the potential benefit of our patients (reference 28 in article). The compassion to treat children and reduce morbidity is the centerpiece of all these endeavors.
A Laparoscopic Approach is Best for Retroperitoneal Lymph Node Dissection Retroperitoneal lymph node dissection continues to evolve as a treatment option for men with testicular cancer. While open RPLND remains the standard for surgical removal of retroperitoneal lymph nodes, use of RPLND has declined recently.1 This has been an appropriate decline for cases better managed with surveillance, but the increase in the use of chemotherapy instead of RPLND may be a disservice to our patients given the now recognized long-term consequences of chemotherapy. When faced with the choice between chemotherapy and open RPLND, many young men may choose chemotherapy to avoid the morbidity associated with open surgery.
A Laparoscopic Approach is Best for Retroperitoneal Lymph Node Dissection The management of testicular cancer is a model for the successful multidisciplinary approach to a solid malignancy, with a projected 95% survival rate for newly diagnosed cases in 2017. With a high likelihood of cure, investigators have focused on treatment related morbidity and maintaining quality of life, and gained insight into previously underappreciated issues, such as late relapse, reoperation and the long-term sequelae of treatment. Radiation and medical oncologists have relied on prospective randomized trials to test the lower bound of efficacy and establish new treatment paradigms, thereby generating Level 1 evidence.
The Nonpalpable Testis: A Narrative Review While the nonpalpable testis represents only a small portion of all cryptorchid testes, it remains a clinical challenge for pediatric urologists. Many controversies about the best evaluation and management exist. This narrative review serves as an update on what is known about the nonpalpable testis: etiology, pre-operative evaluation, the best surgical management, novel techniques, and ongoing controversies.
Reply by Authors We agree that more research is needed to solidify the role of the calcium-to-citrate ratio in predicting kidney stone recurrence in children. However, we want to clarify that although patients had received dietary advice, they were not administered pharmacological intervention during the observation period before collection of the 24-hour urine for metabolic profile.
Editorial Comment Prognostic factors predicting kidney stone recurrence in the pediatric population are lacking. Management decisions made in pediatric stone formers are often guided by adult data. Children have important differences in urinary risk factors relative to adults.1
Reply by Authors Thank you for your shared interest in US for this patient population. Our findings that the majority of patients who undergo initial US did not go on to require CT was somewhat surprising when looking through the eyes of the urologist. Due to the known limitations of US, urologists often use the information provided by CT (stone size, number, location and density) to help guide management. In addition, the finding of hydronephrosis on ultrasound, which serves as a surrogate for ureteral stone obstruction, is not always predictive of such.
Editorial Comment The authors present a single institution, retrospective review of more than 10,000 stone episodes. Overall 20% of subjects underwent renal ultrasound as the first imaging and 80% of this group avoided CT entirely. It is unclear whether these trends are representative of other institutions but they provide an example of what is possible with a commitment to using ultrasound as a first line diagnostic test for stones.
This Month in Adult Urology When partial nephrectomy is planned, conversion to radical nephrectomy is a possibility regardless of surgical approach. With a laparoscopic or robotic approach, complete kidney removal typically can be accomplished without conversion to open surgery. In this retrospective analysis of 1,023 planned robotic partial nephrectomies by Kara et al (page 000) from Cleveland, Ohio conversion to radical nephrectomy was necessary in 32 patients (3.1%).1 Tumor related factors, such as hilar involvement, positive margins or advanced disease stage, were the most common reasons for conversion but failure to improve was the reason in 5 cases.
This Month in Pediatric Urology Although typically thought of as an adult issue, management decisions of pediatric conditions, such as varicocele surgery and exposure to gonadotoxins, in childhood and adolescence can have direct consequences as well as long-term effects on fertility. Currently, for these patients the options are limited but there are now advances in fertility preservation which hold great promise.
Re: Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer W. U. Shipley, W. Seiferheld, H. R. Lukka, P. P. Major, N. M. Heney, D. J. Grignon, O. Sartor, M. P. Patel, J. P. Bahary, A. L. Zietman, T. M. Pisansky, K. L. Zeitzer, C. A. Lawton, F. Y. Feng, R. D. Lovett, A. G. Balogh, L. Souhami, S. A. Rosenthal, K. J. Kerlin, J. J. Dignam, S. L. Pugh and H. M. Sandler; NRG Oncology RTOG
Reply by Authors The thoughtful commentaries from Drs. Lemack and Dmochowski raise good followup points regarding the need for longitudinal and investigative studies of patients with chronic urinary retention. When writing this white paper, the CUR workgroup developed a partial list of needed research studies.
Editorial Comment “Dr. Consensus, we just received a referral for man with a PVR of 750 ml. The referring internist is requesting that you place a catheter and see him right away.” How many times have we all received such calls?
Editorial Comment The term “urinary retention” remains a poorly defined conceptual construct, enshrouded in urological lore, encumbered by incomplete evidence and confounded by irrational therapeutic intervention. Historically, this entity has been associated with the absolute requirement for urinary catheterization, and yet more recent experience derived from neurotoxin or neuromodulation clinical experience has identified the variability of an isolated PVR evaluation and subsequent impact on health status. The concern with PVR assessment is its inherent variability in bedside diagnostic methods.
Editorial Comment The field of fertility preservation is gaining a lot of attention. It is likely to continue to expand thanks to the speed of technological advances and increasing awareness of factors that can threaten the future reproductive ability of children and adolescents. The current state of affairs, promising new frontiers and ongoing controversies, is well summarized in this article by Johnson et al.
Re: Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations L. Albiges, A. A. Hakimi, W. Xie, R. R. McKay, R. Simantov, X. Lin, J. L. Lee, B. I. Rini, S. Srinivas, G. A. Bjarnason, S. Ernst, L. A. Wood, U. N. Vaishamayan, S. Y. Rha, N. Agarwal, T. Yuasa, S. K. Pal, A. Bamias, E. C. Zabor, A. J. Skanderup, H. Furberg, A. P. Fay, G. de Velasco, M. A. Preston, K. M. Wilson, E. Cho, D. F. McDermott, S. Signoretti, D. Y. Heng and T. K. Choueiri
Focal Laser Ablation of Prostate Cancer: Feasibility of MRI/US Fusion for Guidance Focal laser ablation (FLA) is a potential treatment for some men with prostate cancer (CaP). As currently practiced, FLA is performed by radiologists in a MRI unit (in-bore). We evaluated the safety and feasibility of performing FLA in a urology clinic (out-of-bore), using magnetic resonance imaging-ultrasound (MRI/US) fusion for guidance.
Editorial Comment OAB is a highly prevalent condition, impacting approximately 16% of adults in the United States and significantly reducing quality of life.1 The recommended treatment options are well described in the AUA (American Urological Society)/SUFU (Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction) OAB guidelines, including tier 1—behavioral therapy, tier 2—oral medications (antimuscarinics and β3-agonists) and tier 3—onabotulinumtoxinA, sacral neuromodulation and PTNS.2 The lack of long-term persistence of the oral medications is well documented.
Editorial Comment Despite evidence of benefit1 tibial nerve stimulation is not widely performed with current technology since the delivery of therapy is often resource intensive and the response is hard to predict. Percutaneous delivery of therapy and application of therapy by the patient potentially could revolutionize the use of tibial nerve stimulation. Needle-free (transcutaneous) stimulation, in which an implant is placed adjacent to the target site, thereby enabling the patient to self-administer tibial nerve stimulation, could clearly have a great impact.
Reply by Authors Our study suggests that urinary levels of IL-6 combined with bedside estimation of WBCs is a promising tool to differentiate ABU from a suspected episode of UTI. It also suggests that IL-6 could serve as a marker of treatment or a wait and see approach in suspected UTI cases. The added value of IL-6 in diagnosing UTI was recently tested in a pilot trial in an ABU prone nursing home population, resulting in a 20% reduction in antibiotic treatments without documented side effects (reference 25 in article).
Editorial Comment Hooton et al confirmed that colony counts of E. coli as low as 10 to 102 cfu/ml in midstream urine were sensitive for presence of E. coli in catheter urine and, thus, diagnostic for lower UTI in symptomatic women.1 However, in the same study no bacteriuria was found in catheter urine in 26% of symptomatic patients. On the contrary, in women with ABU recurrent symptomatic infections may even be prevented if left untreated.2 Thus, the clinical diagnosis of lower UTI has become much more important and a specific questionnaire was established.
Editorial Comment For many years the inappropriate use of antibiotics has been recognized as a major problem, leading to higher health care costs as well as increased antimicrobial resistance.1 On the other hand, no markers predicting the transition from ABU to symptomatic UTI have been available.2 Distinguishing ABU that does not require treatment from symptomatic UTIs may be a key to success for improving antibiotic stewardship (reference 7 in article). A biomarker that could indicate the time to begin antibiotic therapy is highly desirable.
Reply by Authors We agree that it would be important in clinical practice to know the effect of vitamin D supplementation on the risk of recurrence in kidney stone formers. Prior studies of urinary risk factors following vitamin D supplementation in stone formers seem reassuring.1,2 However, we could not evaluate the association between intake of vitamin D and risk of stone recurrence among participants with a history of kidney stones at baseline, since recurrence episodes had not been validated in our cohorts. Furthermore, we usually exclude participants with a history of kidney stones at baseline since the diagnosis of stones can lead to changes in dietary habits before the start of followup.
Reply by Authors Taguchi et al raise 2 points that we would like to address. As they mention, current guidelines advocate initiation of SRT before significant PSA increase. However, the guidelines do not define PSA less than 1 ng/ml as an acceptable limit and, in fact, support our findings regarding earlier initiation of SRT. According to ASCO (American Society of Clinical Oncology) and the AUA/ASTRO (American Society for Radiation Oncology) guideline, SRT is most effective when administered at lower PSA levels.
Reply by Authors Randomized cancer screening trials tend to concentrate on the screening arm because the information is readily available on those who are screened. However, the relative difference between the trial arms (eg in incidence and mortality) appears to be more dependent on the event rate in the control arm. Opportunistic PSA testing has become widespread but the pace and extent of such testing vary among populations. Furthermore, it is not only testing but also the rigor of the diagnostic followup procedures that ultimately affects incidence and mortality.
Editorial Comment Two multicenter trials have investigated the effectiveness of PSA testing on prostate cancer mortality. PLCO was performed in the United States, where PSA testing was widespread, with a 99% intervention rate and an 86% control rate, thus, comparing organized to opportunistic testing.1 This small absolute difference in PSA use lowered study power to detect the postulated expected mortality reduction between the arms.1 In contrast, ERSPC was done in 8 European countries, where PSA testing was initially rare, and it showed significant benefit.
Re: Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival The authors describe their work investigating the optimal definition of early salvage radiotherapy (SRT) following radical prostatectomy (RP) in 657 patients with long-term followup (9.8 years). While current guidelines advocate a pre-radiation prostate specific antigen (PSA) level of less than 1.0 ng/ml,1,2 a growing body of literature demonstrates that early SRT given at PSA 0.5 ng/ml or less is associated with better outcomes.3 However, few studies have investigated “very early” SRT with a pre-radiation PSA level of 0.2 ng/ml or less.
Ultrasound Shear Wave Elastography: A Novel Method to Evaluate Bladder Pressure Children with bladder dysfunction leading to increased storage pressure are at risk for renal deterioration. The current gold standard evaluation is urodynamics, an invasive test requiring catheterization. The aim of this study was to evaluate ultrasound shear wave elastography (SWE) as a novel means to assess bladder biomechanical properties associated with elevated bladder pressure.
Reply by Authors Based on the issues raised by Narayan et al, we wonder whether they reviewed our report thoroughly. The main issue regarding the risk of bias for nonrandomized single group studies must be understood in the context of our hypothesis for this meta-analysis. Our analysis does not aim for the conclusive outcome that includes comparative and noncomparative studies. However, it suggests a new objective context for current evidence and future studies by overcoming previous limitative meta-analyses that used noncomparative studies.
Reply by Authors In this retrospective study there could be various possible confounding factors such as primary and recurrent bladder cancer. Therefore, we analyzed only primary cases as suggested, which showed the significance of AST remained (HR 0.14, p = 0.0064). Also, the interval from previous diagnosis to enrollment could introduce bias leading to a long interval resulting in a low risk of recurrence. However, when investigated, those findings were comparable.
Editorial Comment These authors report on 32 patients with a rare entity, that is PFUD associated with a urethrorectal fistula, which was treated with standard urethroplasty and rectal closure techniques augmented by a gracilis flap. In a notable 30% of patients previous surgery without a gracilis flap failed, which may indicate that a gracilis flap is prudent in all but the smallest and easiest fistulas. The series also establishes that perineal approach urethroplasty and rectal fistula repair are technically feasible without the need for transrectal sphincter surgery, although inferior pubectomy may be required in almost half of the patients.
Editorial Comment Pelvic fractures can occasionally be associated with urethral injury and rectourethral fistulas. These entities are demanding to treat in isolation but even more so when present simultaneously. In this study Guo et al report their experience with bulbomembranous anastomotic urethroplasty with primary rectourethral fistula closure and gracilis interposition performed simultaneously via the perineal approach.
Re: Efficacy and Safety of Prostatic Arterial Embolization: Systematic Review with Meta-Analysis and Meta-Regression Shim et al report the results of a systematic review (SR) and meta-analysis evaluating the current evidence concerning prostatic artery embolization (PAE) for management of obstructive lower urinary tract symptoms. SRs have an important role in informing evidence-based clinical practice in urology. However, to avoid misleading conclusions, investigators should follow rigorous methodological standards such as those set by the Cochrane Collaboration1 and checklists such as the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) criteria.
Reply by Authors We agree with Diamond that the incidence of bilateral varicoceles in our series is a bit higher than in the literature. However, this increased rate does not reflect the prevalence of bilateral varicocele in adolescents. This finding may only reflect the incidence of bilateral varicocele in adolescents who present to our clinics with symptoms. In a previous study we found that the prevalence of bilateral varicocele is 10.8% at age 11 to 19 years (reference 1 in article). In addition, the incidence of bilateral varicocele is as high as 35% to 48% in adolescent varicocelectomy series in the literature (references 14, 17 and 30 in article).
Editorial Comment This provocative long-term controlled study will add to the controversy surrounding the appropriateness of adolescent varicocele repair. The findings strongly suggest that teenage patients benefit from surgery if there is evidence of testicular growth arrest and/or an abnormal semen analysis. Semen parameters, testosterone levels and paternity all appear improved by microscopic inguinal varicocele ligation.
Editorial Comment This is an important study since it adds to the limited literature regarding the impact of surgical correction of adolescent varicocele on future fertility (references 3 and 16 in article). The authors report on a large number of adolescents (408) deemed to be appropriate candidates for varicocele correction, of whom 70% underwent surgery and 30% declined surgery and served as controls. In the 9 to 10-year mean followup the paternity rates and semen parameters were superior in the surgical group.
Editorial Comment The data in this study are congruent with recommendations from the AUA (American Urological Association)/SUFU (Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction) guideline on nonneurogenic overactive bladder in adults (reference 5 in article). In this study individuals randomized to solifenacin or onabotulinumtoxinA 100 U experienced a reduction in incontinence episodes compared to placebo with the greatest improvement reported among individuals receiving onabotulinumtoxinA.
Editorial Comment In contrast to prior work demonstrating centralization of prostatectomies early in the dissemination of robotic techniques (reference 12 in article), these authors describe decentralization during 2009 to 2011, when the proportion of procedures in hospitals where 1 or more were performed per week increased from 15% to 28%. Unfortunately, as noted in the report, the authors were unable to examine this trend for a longer period due to the substantial change in NIS sampling methodology implemented in 2012.
Reply by Authors We understand the comments on our study and the fact that further research should focus on how the spatial distribution of intralesion targets could be determined. However, we believe that this study has finally started to fill a serious lack in targeted biopsy technique.
Editorial Comment The authors aimed to evaluate the minimum core number for better index tumor detection and characterization in 327 patients. Index lesions were sampled with 4 or 6 cores depending on lesion size (8 or less vs greater than 8 mm) using TRUS/MRI fusion guidance. The major positive core prevalence was observed in the center of targets. Gleason score heterogeneity was observed in 12.6% vs 26.4% of 8 or less vs greater than 8 mm targets. A Gleason 4 or greater pattern was more often observed in the center of lesions.
Editorial Comment The results of Porpiglia et al support the current practice at expert centers and are concordant with international recommendations1 and previous surgical studies (reference 24 in article). In MRI/ultrasound fusion targeted prostate biopsies a minimum of 2 cores must be taken per lesion, sampling the lesion center increases the likelihood of finding the highest Gleason pattern and differences in Gleason scores per core are more frequently found in larger lesions.
Editorial Comment It is critical to determine which men truly harbor indolent disease when deciding which men are suitable candidates for active surveillance for low risk prostate cancer. This is especially important for African American men, who have been shown to present with earlier, aggressive disease and are more likely to experience upgrading and biochemical failure after treatment when initially eligible for active surveillance.1,2 A plethora of serum, urine and tissue based tests add incremental value to the predictive ability of the known risk factors of PSA, Gleason sum and clinical tumor classification.
Editorial Comment Urologists performing PN by any approach face similar challenges, which must be articulated to the patient prior to the operation. Potential adverse events include bleeding, urinary fistula formation, infection and conversion to RN (reference 18 in article) if for technical reasons PN cannot be executed. This group of high volume robotic surgeons reports their RN conversion rate of 3.1% and the patients most likely to require conversion due to worse baseline kidney function, larger tumor size and greater tumor complexity.
Editorial Comment Robotic partial nephrectomy has advanced significantly. Early in its evolution cautious application dictated that complex tumors were avoided. Now with experience there are few, if any, tumors not amenable to RPN when OPN is possible, although not for all surgeons and institutions.
Robotic Intracorporeal Continent Cutaneous Diversion Robotic intra-corporeal urinary diversion has mostly been utilized for ileal conduit or orthotopic neobladder diversion. Herein, we present the initial series, detailed technique and outcomes of robotic intra-corporeal Indiana pouch, with minimum 1-year follow-up.
The Importance of Peer Review Winston Churchill is quoted as saying “Democracy is the worst form of government except all the others.” A similar sentiment about the peer review process for evaluating scientific manuscripts is often expressed by many. However, the fact is no alternative system has been developed which has proven to be superior to peer review, which is considered the backbone of scientific and medical research.
A Pediatric Urology Wish List for Spina Bifida Research The long-term prognosis for children with spina bifida (SB) has greatly improved in the last 50 years.1 Until the latter half of the 20th century children with SB infrequently lived to adolescence. In the early part of the 21st century adults with SB are now so numerous that urologists struggle with how best to cope with a “tidal wave” of patients with SB who have aged out of pediatric clinics.2 In the 1970s ileal conduits represented state-of-the-art urological care for patients with SB. In 2017 incontinent diversions are used only rarely.
Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation for Primary Vesicoureteral Reflux in Children The study by Boysen et al (page 1555) in this issue of The Journal represents a great step in helping us answer lingering questions regarding the current efficacy and safety of robot-assisted laparoscopic extravesical ureteral reimplantation (RALUR-EV) for the treatment of vesicoureteral reflux (VUR) in children.1 We praise the many contributors who embarked on this multi-institutional study with good intentions. It is imperative that we examine competitive surgical options concerning “QCCC” yield, ie quality (success and complication rate), convalescence (with associated pain medication requirements), cost and cosmesis.
2016 Journal of Urology Peer Reviewers Below is the list of peer reviewers who reviewed manuscripts for The Journal of Urology® in 2016 and who submitted their reviews on time. Our peer reviewers give their time, expertise and advice generously and objectively to the editors and authors. All participants in the process benefit from this interchange, and the readers benefit from the improved communications that result. We all owe these individuals a debt and our thanks.
This Month in Pediatric Urology There has been a great deal of interest in the potential benefit of in utero myelomeningocele closure since the MOMS (Management of Myelomeningocele Study) trial was published in 2011. This prospective trial demonstrated a significant reduction in the need for ventriculoperitoneal shunting and improved motor skills for patients who had undergone prenatal closure. Unfortunately there has not been equivalent improvement in the urological outcome for these children.
Choosing the Right Intervention for Treatment of Lower Urinary Tract Symptoms in Men Without ever being subjected to the scrutiny that has been expected of subsequent treatment innovations, transurethral resection of the prostate (TURP) came to be regarded as the gold standard surgical treatment for benign prostatic hyperplasia (BPH). The only randomized controlled trials that have properly scrutinized TURP have been those in which TURP was the control rather than the experimental arm of the study.
Editorial Comment This comparison paper of urine biomarkers between sacral neuromodulation and botulinum toxin injection for refractory OAB, which is based on another excellent study,1 has several stimulating findings that I like to highlight.
Editorial Comment Previously we have enthusiastically searched for urinary proteins to diagnose functional disorders of the bladder. To date no 1 biomarker has proved superior to the cardinal symptoms of the disease. The wide variability of urinary protein concentrations might result from different investigating methodology, urine collection and most likely the heterogeneity of the disease. OAB is a dynamic disorder and the symptoms may change with time.1 Previous studies have shown that functional alterations in urothelium, detrusor, sensory afferents or central nervous system, or inflammation might contribute to the development of OAB.
Re: Mortality among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial T. J. Johnston, G. L. Shaw, A. D. Lamb, D. Parashar, D. Greenberg, T. Xiong, A. L. Edwards, V. Gnanapragasam, P. Holding, P. Herbert, M. Davis, E. Mizielinsk, J. A. Lane, J. Oxley, M. Robinson, M. Mason, J. Staffurth, P. Bollina, J. Catto, A. Doble, A. Doherty, D. Gillatt, R. Kockelbergh, H. Kynaston, S. Prescott, A. Paul, P. Powell, D. Rosario, E. Rowe, J. L. Donovan, F. C. Hamdy and D. E. Neal; ProtecT Study Group
Organ Sparing Surgery in Penile Cancer: A Systematic Review Although penile cancer (PC) only represents 1% of all male cancers, the traditional treatment of total or subtotal penectomy carries devastating psychological and functional outcomes. Organ sparing surgery (OSS) in PC is an attractive option if it can provide satisfactory cancer control equivocal or near equivocal to standard techniques. In fact, these techniques are meeting increasing acceptance. Accordingly, the need to evaluate these options objectively is crucial in a comprehensive review is timely in order to increase awareness of these procedures, their applicability and provide guidance to the practicing urologist.
Penile Allotransplantation for Complex Genitourinary Reconstruction Reconstruction of complex functional structures is increasingly being performed with vascularized composite allo-transplantation (VCA). Penile transplantation is a novel VCA treatment option for severe penile tissue loss and disfigurement. Three allogeneic human penile transplantations have been reported. We review these cases as well as penile transplant indications, pre-clinical models, and immunosuppression therapy.
Cytoreductive Nephrectomy Renal Cell Carcinoma Patients with Venous Tumor Thrombus Careful selection is critical to identify metastatic renal cell carcinoma (mRCC) patients who are most likely to benefit from cytoreductive nephrectomy (CN). Surgery for mRCC patients with tumor thrombus is complex and may not benefit some patients with very poor overall survival (OS). The objective of this study was to evaluate whether preoperative variables or risk stratification systems could predict OS following CN.
Reply by Authors After stratification based on molecular status of a previous tumor, the assay combination had a cross-sectional sensitivity of 62%. When we consider the anticipatory effect over the first 12 months after the positive urine test, sensitivity would increase to 69% for the 3-assay combination. In addition, most aggressive recurrences were detected by the combination with a cross-sectional sensitivity of 83% for stage T1 or greater, or grade 3 recurrences.
Editorial Comment The suggestion that this biomarker combination could be used as an alternative to cystoscopy for low grade bladder cancer challenges current practice. AUA (American Urological Association) guidelines suggest that biomarkers should not be used in place of cystoscopy, and patients with low risk tumors need infrequent cystoscopic surveillance and do not require routine biomarker testing.1 The findings of 57% sensitivity and 59% specificity for surveillance of low grade bladder cancer is a modest improvement over a coin toss.
Editorial Comment The search for reliable urine based tests to identify (recurrent) bladder tumors has been a disappointing journey. Different markers have been evaluated with a wide range of sensitivities and specificities, probably based on patient selection and concomitant intravesical treatment. This is the reason why these markers are not included in guidelines and only cytology is mentioned in recommendations.
Re: Can Activities of Daily Living Predict Complications following Percutaneous Nephrolithotomy? Leavitt et al evaluated whether deficits in activities of daily living (ADLs) could predict complications after percutaneous nephrolithotomy, and how this prediction compares to the Charlson comorbidity index (CCI) and American Society of Anesthesiologists® (ASA®) classification. The authors concluded that ADLs are easily evaluated preoperatively and independently predict complications following percutaneous nephrolithotomy better than CCI or ASA classification.
Reply by Authors In support of the comment, the performance by Cxbladder in a mitomycin treatment setting is comparable with the overall performance of the test. We identified 74 cases in our clinical trial database in which treatment with mitomycin had been prescribed prior to presentation and urine sampling. In this set of patients Cxbladder Monitor had 91.6% sensitivity and 94.4% negative predictive value.
Editorial Comment The authors present an interesting analysis of a noninvasive urine test for monitoring patients with bladder cancer after transurethral resection of the bladder. The goal is to rule out recurrences and potentially reduce the number of cystoscopies. The results seem to be promising, particularly because of high sensitivity for detecting high grade recurrences.
Editorial Comment This collection of RALUR-EV data from 10 surgeons at multiple hospitals is perhaps a better reflection of true success and complication rates of RALUR-EV than previously published series. Unfortunately the 85% success rate of RALUR-EV falls significantly short of the success rates seen in open ureteral reimplantation. In addition, 31 of the ureters operated on (8.6% of total) were reflux grade 0 or I. If those ureters were eliminated from the study, the success rate might be even lower.
Editorial Comment The authors are to be credited for this attempt to benchmark robotic antireflux surgery. This operation has been challenged in its short life with highly variable success rates and nontrivial complications.
Re: Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy The authors performed a multicenter study of urinary DNA biomarkers to predict the risk of bladder cancer in patients with hematuria. Six DNA mutations and methylation biomarkers (FGFR3, TERT, HRAS, OTX1, ONECUT2 and TWIST1) were combined as a panel for diagnosis. This study provided more evidence regarding the accuracy of the urinary DNA panel combined with patient age in screening for bladder cancer, and cystoscopy was unnecessary for some individuals presenting with hematuria if the DNA detection was negative.
Reply by Authors The commentator correctly points out the main uncertainties involved with this new treatment from a clinical perspective. Importantly, he reminds us that hemostasis remains an issue following creation of the prostatic cavity by aquablation. The technique of hemostasis used in the current global, phase III study (known as the WATER Study), which has just completed enrollment, now involves catheter traction for 2 hours following surgery with the balloon of the Foley catheter inflated to 50% of the original prostate volume and positioned in the fossa under TRUS guidance.
Editorial Comment The use of a transrectal ultrasound guided, high pressure saline jet to ablate prostatic tissue (termed aquablation) is a highly novel approach for men with symptomatic BPH. Gilling et al report promising outcomes in a small multicenter trial of men with a mean prostate volume of 57.2 cc. The attraction of this technology is the speed with which tissue can be ablated with a mean aquablation treatment time of only 5 minutes. The high pressure saline waterjet is nonhemostatic so that the treatment is paired with standard resectoscope techniques for achieving hemostasis.
A 10-Year Retrospective Review of Nephrolithiasis in the Navy and Navy Pilots Little is known about the incidence of nephrolithiasis in the U.S. Navy, and Navy pilots must be kidney stone-free and are often referred for treatment of small asymptomatic stones. The primary objectives of this study were to determine the incidence of nephrolithiasis, CT scans performed, proportion undergoing treatment, and incidence of stone-related mishaps of Navy pilots compared with other Navy personnel.
Editorial Comment Although it is perhaps a forgotten entity, percussion has been shown to facilitate the passage of stone fragments (reference 13 in article). These authors report a novel percussion machine that creates vibrations to “shake up” stone fragments to improve passage. Similar in concept but using different technology, ultrasonic propulsion has been described to use focused ultrasound to move stones to facilitate passage and potentially relieve obstruction (reference 17 in article).1
This Month in Adult Urology From the earliest descriptions of medical procedures, management of lower urinary tract symptoms (LUTS) from benign prostate enlargement has been an area of controversy. This issue of The Journal of Urology® includes articles on the significant advances in the treatment of LUTS which have been made as well as a variety of available options. There are many ways to eliminate obstructing prostate tissue and which is best depends on a number of factors, including equipment availability, and surgeon preference and experience.
The Role of Intermittent Androgen Deprivation Therapy for Prostate Cancer The rationale for comparing intermittent (IAD) to continuous androgen deprivation (CAD) therapy was based on preclinical data that showed intermittent exposure to testosterone delayed time to castration resistance compared to CAD.1 As originally observed by Klotz et al, an additional benefit of IAD was the return of sexual function during the off treatment periods.2 The 2 largest phase 3 trials, S9346 (NCT00002651) in metastatic disease and NCIC JPR-7 (NCT00003653) in nonmetastatic disease, were based on the hypothesis that overall survival with IAD might at least be noninferior to that of CAD as a result of delaying time to castration resistance and that quality of life (QoL) would be better on IAD.
This Month in Pediatric Urology The pediatric articles in this issue of The Journal are about stone disease and surgical oncology. Like adults, children are now troubled frequently with urinary stones, and a common set of predisposing causes are dietary (hydration and sodium intake). Fortunately, unlike adults, children are not replicating the pattern of urology oncology but for those who do need urology oncology services, we have the results of a survey of the state of affairs in North America.
Outcomes of Prostate Cancer Screening by 5α-Reductase Inhibitor Use Prostate cancer screening with prostate specific antigen reduces prostate cancer mortality but leads to over diagnosis of indolent prostate cancer. The use of 5α-reductase inhibitors lowers prostate specific antigen and in theory could affect the performance of prostate specific antigen based screening. We evaluated the outcomes of prostate cancer screening in 5α-reductase inhibitors users.
Zinc as a Contributing Factor in Lithogenesis: Not Yet Ready for the Clinic Kidney stones are increasingly prevalent in children and adults, with associated estimated yearly health care costs in the United States exceeding $5 billion.1 Environmental and particularly dietary factors have a role in the risk of kidney stones. There is substantial evidence that decreased fluid, calcium and potassium intakes are major contributors to stone formation. On the other hand, evidence regarding the role of trace minerals such as zinc is quite scarce. In rats zinc has been shown to affect mineral metabolism and potentially stone formation by reducing deposition of calcium salts in the renal papillae.
News and Announcements President – Dr. Richard K. Babayan, 725 Albany St., Ste 3 B, Boston, Massachusetts 02118
Bladder capacity is a biomarker for a bladder-centric versus systemic manifestation in interstitial cystitis/bladder pain syndrome Interstitial cystitis/bladder pain syndrome (IC/BPS) presents a significant clinical challenge due to symptom heterogeneity and the myriad associated comorbid medical conditions. We recently reported that diminished bladder capacity (BC) may represent a specific IC/BPS sub-phenotype. The objective of this study is to investigate the relationship between anesthetic bladder capacity and clinical findings (urologic and non-urologic) in a cohort of IC/BPS patients who had undergone therapeutic urinary bladder hydrodistention.
Editorial Comment Because data supporting the use of AS have been derived from predominantly Caucasian cohorts, the appropriateness of AS in the African American population remains a subject of debate.1 These authors present outcomes in 234 men treated with AS in the French West Indies, where more than 90% of the population is of African descent. In a population in which 81% of individuals are at very low risk, the authors observed extremely low rates of metastasis (0.4%) and PCa mortality (0%) over a median followup of 4 years, consistent with findings in Caucasian men at similar risk (reference 5 in article).
Editorial Comment Ethnic disparity in men with newly diagnosed PCa is an increasingly important issue in the United States. These authors studied a cohort of mostly nonHispanic African Guadaloupian men, of whom 81.2% qualified for very stringent AS criteria composed of a hybrid of original Epstein and NCCN definitions of very low risk PCa. PSA density was the only finding that strongly predicted AS termination but it was not part of the AS selection criteria.
Editorial Comment Tan et al provide an interesting contribution to the urological health services literature on functional status and kidney cancer surgery. Using SEER-Medicare data, they found that poor functional status is independently associated with increased medical and geriatric complications but not with surgical complications after surgery. Resource utilization is higher in patients with worse functional status.
Editorial Comment In this article Tan et al provide a perspective on frailty as a determinant of value in treatment for renal cell cancer. Given the recent growth of advanced treatment modalities such focal therapy and robotic surgery, and more conservative approaches like active surveillance, there is a need to account for the value of renal cancer care. This will be especially important in coming years when alternative payment models such as bundled payments may make urologists accountable for outcomes and costs.
Re: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer Data are lacking for patient reported outcome measures comparing treatments for clinically localized prostate cancer. These authors compared patient reported outcomes in 1,643 men in the ProtecT trial, who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and yearly thereafter. Patients completed validated measures that assessed urinary, bowel and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer related quality of life was assessed at 5 years.
Re: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer J. L. Donovan, F. C. Hamdy, J. A. Lane, M. Mason, C. Metcalfe, E. Walsh, J. M. Blazeby, T. J. Peters, P. Holding, S. Bonnington, T. Lennon, L. Bradshaw, D. Cooper, P. Herbert, J. Howson, A. Jones, N. Lyons, E. Salter, P. Thompson, S. Tidball, J. Blaikie, C. Gray, P. Bollina, J. Catto, A. Doble, A. Doherty, D. Gillatt, R. Kockelbergh, H Kynaston, A. Paul, P. Powell, S. Prescott, D. J. Rosario, E. Rowe, M. Davis, E. L. Turner, R. M. Martin and D. E. Neal; ProtecT Study Group
Reply by Authors This study was part of a larger evaluation that included a controlled assessment of bowel functional outcomes in patients with ARMs treated with modern repairs.1–4 A high response rate was one of the strengths of this study, for which we can only thank our patients. Regarding choice of survey for erectile function, the Erection Hardness Score has been validated,5 and yields similar information to IIEF-5. Importantly we ascertained that erectile function sufficient for penetration was preserved in patients even with the most severe type of ARM (RUF) after posterior sagittal anorectoplasty.
Reply by Authors Ramos and Yu highlight the importance of a more targeted approach to thromboembolism prophylaxis in patients with bladder cancer. Bladder cancer is the second most common malignancy (after esophageal cancer) associated with high rates of postoperative TEEs.1 In our study additional risk of TEEs was posed in these patients by the application of platinum based neoadjuvant chemotherapy. Extended period thromboembolism prophylaxis following abdominopelvic cancer surgeries has been observed to reduce the incidence of venographically demonstrated thrombosis,2 and there are indications that extended VTE prophylaxis following radical cystectomy is warranted.
Editorial Comment Is a competitive spirit enough to improve one’s surgical outcomes? Does the Hawthorne effect truly impact surgical technique? In this innovative study, the authors implemented a CQPR strategy (reference 1 in article), a method that drives improved clinical performance by informing clinicians of their outcomes and those of their colleagues. Using 2 oncologic quality indicators, the investigators compiled surgeon score cards including 2 years of radical prostatectomy risk adjusted outcome data for each surgeon in the study.
Re: Multilocular Cystic Renal Cell Carcinoma: Pathological T Staging Makes No Difference to Favorable Outcomes and Should be Reclassified We studied in detail this publication describing 168 cases of renal tumor excision with long followup. The authors group these cases together based on the cystic architecture, referring to them as cystic renal cell carcinoma (RCC), and suggest that pathological tumor stage does not influence outcome in multilocular cystic (mc) RCC and needs to be reclassified. Although we support their observation regarding favorable prognosis with multilocular cystic renal neoplasm of low malignant potential (MCRNLMP, formerly mcRCC),1 we must comment on some aspects of the study from a pathology standpoint.
Trends in Imaging Use for the Evaluation and Followup of Kidney Stone Disease: A Single Center Experience Recent reports support renal ultrasound as the initial imaging study to evaluate patients with suspected renal colic. However, urologists often advocate for computerized tomography to better define stone size and location, especially before proceeding with endourological intervention. One concern with using ultrasound as initial imaging is that computerized tomography may be required later, obviating the reduction in costs and radiation gained by using ultrasound.
Triggered Urine Interleukin-6 Correlates to Severity of Symptoms in Nonfebrile Lower Urinary Tract Infections Objective diagnosis of symptomatic urinary tract infections in patients prone to asymptomatic bacteriuria is compromised by local host responses that are already present and the positive urine culture. We investigated interleukin-6 as a biomarker for nonfebrile urinary tract infection severity and diagnostic thresholds for interleukin-6 and 8, and neutrophils to differentiate between asymptomatic bacteriuria and urinary tract infection.
Editorial Comment The authors have assembled data supporting a hypothesis, and a widely held perception among pediatric urologists, that the volume of oncologic surgeries being done by pediatric urologists is quite low. This finding is not a surprise. There are a lot of surgeons and not many tumors. The cited studies (references 3 to 5 in article), along with a more recent report,1 suggest that there are at most small differences in outcomes between high and low volume hospitals. There do appear to be significant differences in outcomes between Children’s Oncology Group and nonChildren’s Oncology Group affiliated hospitals.
Editorial Comment In 2014 the Pediatric Urologic Oncology Working Group emailed a survey to Society for Pediatric Urology members concerning participation in oncology care. Of 200 responding pediatric urologists 22% denied performing cancer surgeries, in contrast to the 53.4% noted in the present study. While 25% of survey respondents claimed more than 6 surgeries, this study found that 4 cases comprise the 95th percentile for oncology volume.1 This discrepancy suggests recall bias by survey participants or sample biases within the case logs.
Reply by Authors Stepwise modular learning has been used to teach robot-assisted radical prostatectomy. The main challenge for establishing the reliability of some technically challenging steps is that the opportunity to perform these steps is given to trainees only when their surgical skills are almost at par to faculty performance. This difference was not noticeable in our study, probably due to small sample size. Crowd scoring is ineffective to assess the key technical nuances of any advanced surgical technique, although it may be effective to assess basic robot-assisted surgical skills.
Editorial Comment The methodology for the development of this procedure specific, objective tool to assess surgical skills for RARP should be commended despite some limitations to this study. During construct validation, only 4 of the 7 steps were significantly different between trainees and attending surgeons. A larger multi-institutional study should help with further validation of this tool. The potential to use this tool for milestones during residency training is appealing.
Editorial Comment Critical to the development of any surgical training program is the ability to objectively and reliably measure performance.1 These authors present the development of a procedure specific assessment tool for use during robotic prostatectomy. They provide a robust framework for iterative consensus development using Delphi methodology. The preliminary data on validity and reliability appear promising. However, external validation across a wider range of skill levels is needed to confirm its utility.
This Month in Adult Urology Physicians in general and surgeons in particular are noted for being independent and resistant to being told what to do. Increasingly, though, third party payers and regulatory agencies are using measurements of physician practice patterns and results to provide financial rewards and, sometimes, punitive actions. Beyond any incentive based programs is the potential influence of the observer effect. Sometimes called the “Hawthorne effect,” this principle contends that individuals may modify their behavior, potentially in a positive manner, simply because they are aware that they or their results are being observed.
Penile Cancer: Contemporary Lymph Node Management In penile cancer, the optimal diagnostics and management of metastatic lymph nodes are not clear. Advances in minimally invasive staging, including dynamic sentinel lymph node biopsy, have widened the diagnostic repertoire of the urologist. We aimed to provide an objective update of the recent trends in the management of penile squamous cell carcinoma, and inguinal and pelvic lymph node metastases.
Estimate of Opportunistic Prostate Specific Antigen Testing in the Finnish Randomized Study of Screening for Prostate Cancer Screening for prostate cancer remains controversial, although ERSPC (European Randomized Study of Screening for Prostate Cancer) showed a 21% relative reduction in prostate cancer mortality. The Finnish Randomized Study of Screening for Prostate Cancer, which is the largest component of ERSPC, demonstrated a statistically nonsignificant 16% mortality benefit in a separate analysis. The purpose of this study was to estimate the degree of contamination in the control arm of the Finnish trial.
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