Editorial Comment This large experience by Li et al highlights many dilemmas faced by patients in whom UTUC develops after cystectomy and it brings to the forefront prior observations that cystectomy is an important predictor of poor prognosis in patients with UTUC (references 2 and 3 in article).1,2 Post-cystectomy UTUC was frequently found in this study to be associated with locally advanced and lymph node metastatic disease. When nephroureterectomy was the initial treatment, subsequent chemotherapy was incapable of salvaging cases.
Reply by Authors Curvature less than 30 degrees can cause sexual dysfunction for the patient and/or his partner. However, 30 degrees is important because lesser curvature can be reliably straightened by dorsal plication, while 30-degree or greater bending corrected by plication is more likely to recur. Consequently, whether curvature is less than or greater than 30 degrees determines if the urethral plate is conserved or transected for TIP or STAG repair, respectively. Thus, we correct all ventral curvature but the means to do so vary by the extent.
Editorial Comment Successful hypospadias repair must address associated anomalies and, thus, is defined in part by ventral curvature. Despite the importance of chordee in determining the type of repair, outcomes are limited by an ambiguous definition of what constitutes substantial curvature. The authors describe their experience with STAG in patients with proximal hypospadias and 30-degree or greater VC, and report high success rates. In a survey of American Academy of Pediatrics Section on Urology members, the majority defined significant chordee as curvature greater than 20 degrees and 75% indicated they would proceed with direct intervention.
Reply by Authors The question of whether it is necessary to remove the entire seminal vesicles has thread through the urological literature for more than 20 years,1 initially to clarify the risk of recurrence in cases in which complete removal was unintentionally not achieved and more recently due to observational data suggesting potential functional benefits associated with limited dissection and subtotal removal (references 12 and 13 in article). A number of pelvic anatomical studies have delineated the course of the pelvic sympathetic and parasympathetic nerve fibers in relation to the base of the prostate and seminal vesicles, including the study cited by Costello (references 10 and 11 in article).
Editorial Comment Somehow over the years as radical prostatectomy surgery was developing and improving a hypothesis was formed that by sparing the tips of the seminal vesicles improvements in functional outcomes occurred. There was no anatomical basis for this hypothesis. Our anatomical studies at Royal Melbourne Hospital in 2004 demonstrated the location of the parasympathetic and sympathetic components of the neurovascular bundle (reference 11 in article). The hypogastric nerve supplies sympathetic intervention to the neurovascular bundle.
Prostate Arterial Embolization is a Viable Option for Treating Symptoms of Benign Prostatic Hyperplasia The need for new minimally invasive techniques to treat lower urinary tract symptoms secondary to benign prostatic hyperplasia is demonstrated by the numerous publications on this subject every year and supported by the American Urological Association.6 Among the recent minimally invasive procedures to be developed in this area are Rezūm (NxTHERA, Maple Grove, Minnesota), UroLift® (NeoTract, Pleasanton, California) and prostate artery embolization. PAE has been accepted as a viable treatment for prostate related hematuria for a number of years with hundreds of cases published in the literature.
Prostate Arterial Embolization is a Viable Option for Treating Symptoms of Benign Prostatic Hyperplasia When I was in medical school and contemplating what specialty to enter, one of my mentors strongly advised me to stay away from urology. I can almost hear the words today telling me about a new pill being developed that would shrink the prostate and eliminate all surgeries for benign prostatic hyperplasia (BPH). That pill, finasteride, has undergone its own tumultuous story and clearly was not a panacea for BPH. The overwhelming take home message is that “shrinking the prostate” is not the Holy Grail of treating lower urinary tract symptoms (LUTS).
Editorial Comment The 7-item self-administered AUA-SS has stood the test of time and become a worldwide standard to measure the burden of lower urinary tract symptoms among men with LUTS attributable to BPH. However, in several studies, including this one, men with lower health literacy have had problems understanding and completing AUA-SS. One approach to this problem is an interviewer administered AUA symptom index.1 As outlined in this report, another approach is to develop alternative measures such as FLOW, which are easier for such men to understand.
Editorial Comment Patients with high risk prostate cancer undergoing active treatment exhibit highly variable oncologic outcomes (reference 8 in article). A North American study suggested a further stratification of these individuals into high and very high risk groups to address this issue (reference 9 in article). This new classification was adopted by the NCCN guidelines.
Editorial Comment My previous mentor and chairman, Dr. Fray Marshall, used to speak of times past when renal mass equaled radical nephrectomy. However, numerous studies have demonstrated equivalent cancer specific mortality rates for PN compared to RN for clinical T1 tumors.1 While there is significant data on the deleterious effects of RN compared to PN on renal function and cardiovascular risk, the impact on overall mortality is controversial (reference 14 in article). The current thoughtful, retrospective study by Shah et al demonstrates lower recurrence-free survival for PN vs RN in patients with clinical T1 tumors that are up staged to pathological T3a disease.
Editorial Comment Up staging of clinical T1 RCC occurs when tumors invade small branches of renal veins or fat surrounding the kidney. Similar to prior studies (reference 3 in article) Shah et al describe an 11% risk of pathological up staging. Interestingly they found a higher recurrence risk in up staged cases following partial vs radical nephrectomy. After partial nephrectomy most recurrences were local, which may be amenable to curative local therapy and associated with favorable cancer specific survival in the absence of distant metastasis.
Reply by Authors We appreciate the comment and recognize the pioneering work of Dr. Parsons in the 1990s (references 1 and 2 in comment). In our preliminary work principal component analysis and unsupervised hierarchical clustering showed a clear separation between gene expression profiles in bladder biopsy tissues from subjects with low capacity (400 ml or less) compared to those with bladder capacity greater than 400 ml (reference 12 in article). These data are consistent with a bladder centric disease phenotype.
Editorial Comment These authors report BC while under anesthesia in more than 100 patients with IC. Results show that BC was inversely proportional to patient reported symptoms on several questionnaires and to age. The key message is that patients who are older have more bladder symptoms and lower BC, and we reported similar results.1 This message is critical because it emphasizes that IC is a chronic disease that begins when the symptoms are milder and intermittent. With time symptoms increase and bladder capacity decreases because the disease is destroying the bladder.
Editorial Comment While I am enthusiastic about focal ablation for prostate cancer based on personal clinical experience, there are many unresolved issues, including selection of candidates, extent of ablation, posttreatment assessment of oncologic control and the optimal energy source. Unfortunately the authors do not address these fundamental issues.
Rates and Risk Factors for Opioid Dependence and Overdose After Urologic Surgery Effective pain management is a critical component of the perioperative process, with opioids representing a mainstay of therapy. The opioid epidemic is a growing concern in the United States. The goal of this study was to quantify the risk of opioid dependence or overdose (ODO) among patients undergoing urologic surgery and to identify risk factors of ODO.
Editorial Comment MUSIC is an important health quality initiative in our field. This latest study reveals a surprisingly low 7.8% rate of repeat prostate biopsy in men with multifocal HGPIN or ASAP on initial biopsy, which is recommended under the most recent NCCN guidelines (reference 6 in article). Is this yet another example of suboptimal compliance with guideline or best practice driven care?
This Month in Pediatric Urology Evaluation of neuropathic and nonneuropathic bladder abnormalities in children has centered around the use of invasive urodynamics to determine bladder storage pressures and long-term renal risk. In the absence of alternative testing options some of these patients will be subjected to multiple urodynamic studies to evaluate treatment outcomes and changes. One of the newer ultrasound technologies successfully used in evaluation of other solid organs is ultrasound shear wave elastography (SWE). Sturm et al (page 000) from Chicago, Illinois present data from a pilot study measuring SWE values at different bladder filling volumes during standard urodynamic studies in 23 patients.
This Month in Adult Urology As I reviewed articles published in The Journal of Urology® in the last 100 years to prepare the Centennial issue, it was apparent that urological surgeons have been at the forefront of technical surgical advances since the inception of the specialty. This issue of The Journal, a few months over 100 years since the first, confirms that trend is continuing.
AUA Standard Operating Procedure for MRI of the Prostate The purpose of this review is to summarize the available data about the clinical and economic effectiveness of MRI in the diagnosis and management of prostate cancer and to provide practical recommendations for the use of MRI in the screening, diagnosis, staging and surveillance of prostate cancer.
Renal Mass and Localized Renal Cancer: AUA Guideline This AUA Guideline focuses on evaluation/counseling and management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.
Adjuvant therapy for high-risk localized kidney cancer– emerging evidence and future clinical trials We will review the literature on adjuvant therapies for patients with high-risk localized kidney cancer following surgical treatment. Two recently published prospective trials with conflicting results will be reconciled within the context of their respective designs. Finally, we will spotlight upcoming trials that use novel immunotherapy-based checkpoint inhibitors and have the potential to establish a new standard of care.
Reply by Authors If a varicocele is present, we are likely to recommend microsurgical repair as a treatment option because of the low recurrence rate (0.2%). We have observed no testicular atrophy in our experience with 1,500 microsurgical VRs. This repair can be accomplished in a 30-minute operation and is covered by insurance. Establishing useful tools to predict the improvement of spermatogenesis and avoid unnecessary surgery has been an important issue for a long time.
Re: Predictive Factors for Sperm Recovery after Varicocelectomy in Men with Nonobstructive Azoospermia Currently there are few options beyond surgical sperm retrieval to help patients with nonobstructive azoospermia (NOA) achieve pregnancy. In the clinic setting when we encounter a patient with NOA and varicocele, we ask ourselves, would this patient benefit from a varicocele repair (VR)? Also, what are the chances that this patient will have sperm in the ejaculate? In a meta-analysis by Weedin et al men with hypospermatogenesis on testis biopsy done at varicocele repair had the best chances of having sperm in the ejaculate, compared to those with Sertoli cell only syndrome (SCO) or maturation arrest (MA).
Reply by Authors We understand the view of Shah and Ioffe regarding the Prostate Health Index, that biopsy pathology is not the ideal end point for studies of prostate cancer markers.1 Biopsy pathology and the alternative suggested by Shah and Ioffe, ie radical prostatectomy pathology, are surrogate end points. This is why we have examined the value of the kallikrein panel for the clinically significant end point of long-term metastasis in men followed without screening or biopsy. We found that in men with increased prostate specific antigen (PSA) the panel had predictive discrimination of 0.87 for the long-term prediction of metastasis, compared to 0.81 for PSA alone.
Reply by Authors The most important principle of surgical prophylaxis is that it should prevent serious infection. To achieve this it should cover the potential pathogens and be present in adequate concentrations at the time of the procedure. Unfortunately the convenience of fluoroquinolones and the current AUA (American Urological Association) recommendations1 encourage the use of these agents, which are often administered for several days (reference 5 in article) and are much more likely to generate resistance than a single dose of carbapenem (reference 23 in article).
Editorial Comment An antimicrobial used for surgical prophylaxis should be administered for the shortest effective duration to minimize adverse effects, cost and the development of resistance.1 Ertapenem, a broad-spectrum agent from the carbapenem class for surgical prophylaxis, would seem to violate this principle.
Reply by Authors As noted in the discussion section, we are aware of the research of Shepard et al, in which they did not find a correlation between SWS and bladder compliance (reference 26 in article). The reasons for the discrepancy between our results and those obtained in their series are not entirely clear and deserve further investigation. Key differences in the methods between these 2 studies include variability between devices by manufacturer, the location of measurements on the bladder wall and the measurements of SWS at specific well-defined bladder volumes.
Editorial Comment Because urodynamic testing is invasive, there has been great interest in finding another modality for evaluating bladder compliance. Ultrasound SWE measures tissue fibrosis in situ. Since bladder fibrosis can cause poor compliance, this technology seems promising and may be a significant advance. The authors obtained SWS in 23 pediatric patients undergoing concurrent urodynamics. They found a significant correlation between bladder compliance and mean SWS of the anterior bladder wall.
Editorial Comment This retrospective study of almost 700,000 Navy personnel in a 10-year period examined stone disease among pilots. The issue deserves special attention. In civilians stones cause morbidity and pain (reference 3 in article) but among military pilots stones can be career and life altering. Currently Navy pilots can be grounded for even asymptomatic stones. This implies significant military costs and exposure of young, healthy individuals to potentially unnecessary surgery (reference 22 in article).
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 30) 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 resulting in increased storage pressure are at risk for renal deterioration. The current gold standard for evaluation of bladder pressures is urodynamics, an invasive test requiring catheterization. We evaluated ultrasound shear wave elastography as a novel means of assessing bladder biomechanical properties associated with increased 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 intracorporeal urinary diversion has mostly been done for ileal conduit or orthotopic neobladder diversion. We present what is to our knowledge the initial series, detailed technique and outcomes of the robotic intracorporeal Indiana pouch with a minimum 1-year followup.
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 allotransplantation. Penile transplantation is a novel vascularized composite allotransplantation 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, preclinical models and immunosuppression therapy.
Cytoreductive Nephrectomy for Renal Cell Carcinoma Patients with Venous Tumor Thrombus Careful selection is critical to identify those with metastatic renal cell carcinoma who are most likely to benefit from cytoreductive nephrectomy. Surgery in patients who have metastatic renal cell carcinoma with tumor thrombus is complex and may not benefit some patients with poor overall survival. We evaluated whether preoperative variables or risk stratification systems could predict overall survival following cytoreductive nephrectomy.
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 United States Navy. 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 and computerized tomography, proportion undergoing treatment and incidence of stone related mishaps in Navy pilots compared with other Navy personnel.
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.
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.
Bladder Capacity is a Biomarker for a Bladder Centric versus Systemic Manifestation in Interstitial Cystitis/Bladder Pain Syndrome Interstitial cystitis/bladder pain syndrome presents a significant clinical challenge due to symptom heterogeneity and the myriad associated comorbid medical conditions. We recently reported that diminished bladder capacity may represent a specific interstitial cystitis/bladder pain syndrome subphenotype. The objective of this study was to investigate the relationship between anesthetic bladder capacity, and urological and nonurological clinical findings in a cohort of patients with interstitial cystitis/bladder pain syndrome who had undergone therapeutic urinary bladder hydrodistention.
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.
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.
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