Re: Evaluation of the Azoospermic Male: A Committee Opinion K. Hwang, J. F. Smith, R. M. Coward, A. Penzias, K. Bendikson, S. Butts, C. Coutifaris, T. Falcone, G. Fossum, S. Gitlin, C. Gracia, K. Hansen, S. Jindal, A. La Barbera, J. Mersereau, R. Odem, R. Paulson, S. Pfeifer, M. Pisarska, R. Rebar, R. Reindollar, M. Rosen, J. Sandlow, D. Stovall and M. Vernon
This Month in Pediatric Urology In this issue of The Journal is an article about the practical aspects of managing the postoperative care of patients who have undergone a complex reconstructive operation, stressing the importance of approaching these patients in a consistent manner to help increase the likelihood of a smooth recovery. The other article in this issue focuses on a rare condition that afflicts only a few hundred patients but the neurourological manifestations suggest that what may be a confusing array of symptoms are traceable to a common root dysfunction in the pontine region of the brainstem.
Editorial Comment Combined performance of prostate MRI and targeted biopsy has been documented to improve diagnosis and risk stratification over standard of care approaches in recent large-scale studies (reference 4 in article).1,2 While there is growing interest in implementing MRI and targeted biopsy into routine practice,3 it is known that such a successful practice model is associated with a learning curve (references 12 and 13 in article).
Editorial Comment Decision aids should ideally promote clinical equipoise. However, the data from this study suggest some variation to which this is applied, given the differing results on how they altered the pre-exposure intent to undergo or recommend PSA screening. Although there was some change of opinion, a common theme is that the pre-exposure intent was unchanged in the majority of individuals who worked through any of these decision aids. The results are somewhat similar to our experience with testing a decision aid in a randomized controlled trial of a controversial aspect of prostate cancer care.
Editorial Comment Despite the mortality benefit of PSA screening1 and the improved specificity of detecting clinically significant disease with advanced imaging2 prostate cancer screening remains controversial because of the over diagnosis of indolent disease and the treatment related impact on sexual and urinary function. The ultimate goal of any cancer screening DA is to promote preference congruent and well informed screening decisions.3 Weiner et al measured the impact of various DAs on prostate cancer screening preferences in nearly 1,330 participants using a randomized survey.
Editorial Comment The authors incorporated MRI findings and MRI targeted biopsy pathology into established nomograms that are widely used for preoperative prediction of adverse pathological features. Rayn et al suggest that MRI targeted biopsy pathology provides significantly improved prognostication of adverse pathology when added to the Partin (reference 3 in article) and MSKCC (reference 4 in article) nomograms.
This Month in Adult Urology Published articles often refer to accepted treatments as the “gold standard,” typically meaning the treatment to which other approaches must be compared. Economists would scoff at such a phrase since gold reserve backing for currency has long been abandoned. Nonetheless, certain therapies are time tested and commonly accepted. One of these, certainly, is radical cystectomy for muscle invasive urothelial cancer of the bladder.
Reply by Authors Pearce et al are looking for a platform to let the urology community know about their observations regarding long-term use of PPS (Elmiron®) and potential ophthalmological complications, so much so that they have used a letter to the editor concerning our recent article on the FDA BRUDAC (Bone, Reproductive and Urologic Drugs Advisory Committee) criteria for interstitial cystitis/bladder pain syndrome as a pretext. While their letter has nothing at all to do with our article, we are happy that they have a chance to present their observations.
Editorial Comment The clinical significance of radiation exposure from imaging remains an area of debate and the authors provide a fresh perspective. Currently we know that radiation effects are cumulative in nature and yet no dose limit exists related to medical imaging and limited data reflect actual patient radiation exposure from imaging.1 The current study contextualizes these uncertain harms in the backdrop of CTU.
Re: FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical Trials: Future Direction for Research We read this article with interest. As mentioned by the authors, only 2 FDA (U.S. Food and Drug Administration) approved therapies for interstitial cystitis/bladder pain syndrome (IC/BPS) currently exist: oral pentosan polysulfate sodium (PPS) and intravesical dimethyl sulfoxide. We wish to alert readers to a concerning new observation of vision threatening retinal changes associated with long-term exposure to PPS. We recently reported our findings of retinal pigmentary changes in 6 patients undergoing long-term therapy with PPS.
Editorial Comment In this retrospective study the NCDB was used to evaluate practice patterns in patients with SRMs less than 4 cm between 2010 and 2014. Following adjustment the authors report a greater increase in the use of RPN or radical nephrectomy compared to AS. This change was significant even in patients who were 75 years of old or older and in those with multiple comorbidities (Charlson comorbidity index 2 or greater).
Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: The Role of a Negative Confirmatory MRI-US Fusion Biopsy Active surveillance (AS) has gained acceptance as an alternative to definitive therapy for many men with prostate cancer (PCa). Confirmatory biopsies to assess the appropriateness of AS are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. Our study sought to determine the prognostic implications of negative multi-parametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) guided fusion biopsy (FB) consisting of extended sextant, systematic biopsy (SB) plus mpMRI-guided targeted biopsy of suspicious MRI lesions.
Reply by Author A recent publication in The Journal demonstrated the opposite findings and showed poor quality of life in patients performing intermittent self-dilation.1 Patients experience pain and discomfort, and have difficulty with urethral self-dilation. They are referred or self-refer to a specialist to discuss surgical options to avoid intermittent catheterization. This finding certainly holds true in my reconstructive practice.
Reply by Authors Our report and others suggest that certain patients with muscle invasive bladder cancer can avoid or defer radical cystectomy following a clinical complete response to neoadjuvant platinum based chemotherapy. Although we observed favorable outcomes in this highly select group of patients, there are several limitations and points of caution that must be acknowledged, as the comments highlight.
Editorial Comment In this cohort of patients with rigorous followup these outcomes are favorable. However, 48% of patients experienced recurrence in the bladder, including 11% with MIBC and 37% with high grade NMIBC. This shortfall in bladder tumor local control is concerning, particularly in this highly selected cohort at centers where there is significant experience with bladder cancer and where hundreds of cystectomies are performed per year. Moreover, these results may not be applicable to the general community.
Editorial Comment As surgeons our job is to intervene where the natural course of disease would lead to worsening illness, suffering and premature death, and observe patients who can be safely surveilled without intervention. Mazza et al present a retrospective series of 148 patients with muscle invasive bladder cancer who elected observation without radical cystectomy after a complete response to neoadjuvant chemotherapy. In a group of carefully selected patients from 2 high volume academic centers treated by 2 experienced surgeons the authors found overall 90% 5-year survival, which is on par with studies of patients who receive NAC with cystectomy.
Re: Moving Beyond an Age-Old Intervention I agree with the author that urethroplasty is the preferred treatment for long or dense strictures. However, most patients have less complex strictures and many prefer a less invasive approach. I have had good results with direct incision or dilation of the stricture followed by a period of intermittent catheterization. Good long-term results are achieved in most patients with this approach, with high patient satisfaction.
Conversion from Cystine to Non-cystine Stones: Incidence and Associated Factors and Objectives: Cystinuric patients are often treated with medical alkanalization and shockwave lithotripsy – both are hypothesized to increase the risk of calcium phosphate stones. We performed a multi-center retrospective review to evaluate whether patients with cystinuria develop stones of other composition and with what frequency.
A contemporary analysis of dual inflatable penile prosthesis and artificial urinary sphincters outcomes Inflatable penile prostheses (IPP) and artificial urinary sphincters (AUS) are used to treat men with erectile dysfunction (ED) and stress urinary incontinence (SUI), respectively. After treatment of prostate cancer, men often experience ED and SUI. Dual prosthetic implantation can improve the quality of life of these men. We evaluated the reoperation outcomes in men who underwent dual implantation compared to each individually.
Editorial Comment The authors provide a retrospective review of a large, prospectively managed database of patients with metastatic renal cell carcinoma in South Korea who received a first line tyrosine kinase inhibitor. In this cohort of more than 1,000 patients the authors found that conditional survival improved with time after initial treatment with the tyrosine kinase inhibitor. This trend was mostly driven by patients with Heng poor risk disease.
Re: The Effect of Nerve Sparing Status on Sexual and Urinary Function: 3-Year Results from the CEASAR Study Avulova et al have performed a noteworthy study assessing the true impact of nerve sparing (NS) on the long-term functional outcomes of radical prostatectomy (RP). Walsh et al described the basic technique of NS RP more than 30 years ago.1 A multitude of studies have subsequently displayed functional improvements to potency and urinary continence (UC) with NS vs non-NS RP.2–4 Yet the effect of NS recently has been called into question.5,6
Editorial Comment The authors report the prospective implementation of an ERAS protocol for children undergoing urinary tract reconstruction with small bowel. In this small-scale study 15 patients treated after implementation of an ERAS protocol had shorter time to flatus, stool and discharge home compared to 15 patients treated before intervention. Although adult focused ERAS protocols have been described for various abdominal surgeries,1,2 this study reveals that an ERAS protocol can be successfully used in children despite the variability in physiology, social factors and evidence strength in the 2 populations.
Editorial Comment “Winds of change” blow for prostate cancer diagnostics. Recently published data from the PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image guidance or Not?) trial clearly emphasize the role of targeted biopsies over systematic biopsies (reference 1 in article). Some are ready to rely on MRI and discard routine systematic biopsies while some are more hesitant and still consider systematic biopsies essential.
Editorial Comment The authors argue against use of the term favorable intermediate risk disease to describe low volume GG2 cancer based on rates of adverse pathology of about 20%, which may not be considered favorable.
Reply by Authors We agree with the comments that there is a clear need for international consensus on hematuria evaluation.1 There remains a lack of consensus on the definition of hematuria. In the United Kingdom the term macroscopic hematuria has been supplanted by visible hematuria as it is easily relatable to patients for whom targeted campaigns to raise awareness of the significance of hematuria are in place.
Editorial Comment This study by Tan et al is a post hoc analysis of 3,556 patients enrolled in the DETECT I prospective multicenter observational study.1 Their goal was to determine whether RBUS could replace CTU for the investigation of patients with microscopic hematuria. The authors found that RBUS can safely replace CTU in patients with microscopic hematuria but CTU should be done to investigate gross hematuria.
Editorial Comment The DETECT I trial is an impressive pragmatic, multicenter, prospective observational trial that seeks to inform current practice regarding the optimal workup of hematuria, which is a common and expensive occurrence. This study adds important evidence to the growing body of literature questioning the usefulness of CTU in the workup of microscopic hematuria as recommended by AUA guidelines (reference 3 in article). Notably guidelines define microscopic hematuria as more than 3 red blood cells per high power field compared to a positive dipstick in DETECT.
Editorial Comment There is no standard of care for biochemical relapse after definitive therapy of prostate cancer. When confronted with treatment options, there are 2 extremes in the patient response, including, “Start ADT to get PSA down under any circumstance” and “Defer ADT for as long as possible.” The former reaction occurs despite education about the long natural history of biochemical relapse without ADT or disease characteristics that support a longer time to metastatic disease, such as longer PSA DT or a Gleason score less than 8.
Impact of Potassium Citrate vs. Citric Acid on Urinary Stone Risk in Calcium Phosphate Stone Formers No medication has been shown to be effective at preventing recurrence of calcium phosphate urinary stones. Potassium citrate may protect against calcium phosphate stones by enhancing urine citrate excretion and lowering urine calcium, but it raises urine pH which increases calcium phosphate saturation and may negate the beneficial effects. Citric acid can potentially raise urine citrate but not pH, and thus may be a useful countermeasure against calcium phosphate stones. We aimed to assess whether these two agents can significantly alter urine composition and reduce calcium phosphate saturation.
Editorial Comment This post hoc analysis of the well-known dietary trial of Borghi et al (reference 15 in article) addresses a knowledge gap regarding whether urinary supersaturation indexes predict kidney stone recurrence. It is important to note that in the original study the 24-hour urine parameters dramatically improved after intervention at week 1 and the improvements were generally sustained in the following years.
Hypospadias—Nature and Nurture Hypospadias is one of the most common conditions encountered and arguably one of the most challenging anomalies to be treated by pediatric urologists. The parental stress associated with this disorder naturally leads parents to ask 2 age-old questions: “Why did this happen?” and “Could this happen again in subsequent offspring?”
Reply by Authors For several decades it has been appreciated that multi-agent cisplatin based chemotherapy leads to a pathological complete response in about 30% to 40% of patients with muscle invasive urothelial cancer of the bladder and such a response confers a highly favorable prognosis. Ironically proving that a pathological complete response has occurred requires surgical removal of the bladder and the potential morbidity associated with the procedure.
Editorial Comment Muscle invasive bladder cancer is a challenging disease to treat. Balancing long-term disease control while minimizing short-term and long-term morbidity and maximizing quality of life is difficult when your tools are relatively toxic systemic chemotherapy, radiation therapy and radical cystectomy. Historically the urological community has been slow to consider alternate treatments compared to radical cystectomy as reflected in the relatively low use of neoadjuvant chemotherapy and trimodal therapy.
Editorial Comment In the current NCDB derived study short-term and long-term outcomes after chemotherapy of MIBC were evaluated in patients who did not undergo cystectomy or radiation after bladder tumor TUR. During a 10-year period 1,538 patients underwent chemotherapy alone after TUR while 17,866 underwent undergone cystectomy with or without chemotherapy. The authors noted that patients who did not undergo cystectomy had lower 30 and 90-day mortality rates than those who underwent cystectomy. The noncystectomy group was older, less insured, more likely to be African American, less likely to receive care at an academic facility and most importantly had poorer overall survival than patients who underwent cystectomy.
Editorial Comment Systemic chemotherapy prior to radical cystectomy has been shown to improve survival in MIBC with the best outcomes in patients who achieve a complete pathological response (pT0) (reference 8 in article). The current data from Audenet et al suggest that chemotherapy alone in select patients without cystectomy may result in up to 36% 5-year survival. The implication is that cystectomy can be safely delayed or even eliminated in some individuals with MIBC. However, these results must be interpreted with caution.
Re: MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis V. Kasivisvanathan, A. S. Rannikko, M. Borghi, V. Panebianco, L. A. Mynderse, M. H. Vaarala, A. Briganti, L. Budäus, G. Hellawell, R. G. Hindley, M. J. Roobol, S. Eggener, M. Ghei, A. Villers, F. Bladou, G. M. Villeirs, J. Virdi, S. Boxler, G. Robert, P. B. Singh, W. Venderink, B. A. Hadaschik, A. Ruffion, J. C. Hu, D. Margolis, S. Crouzet, L. Klotz, S. S. Taneja, P. Pinto, I. Gill, C. Allen, F. Giganti, A. Freeman, S. Morris, S. Punwani, N. R. Williams, C. Brew-Graves, J. Deeks, Y. Takwoingi, M.
Cost-Effectiveness of SelectMDx in Prostate Cancer Risk Assessment SelectMDx is a panel of urinary biomarkers used in conjunction with traditional risk factors to individualize risk prediction for clinically significant prostate cancer. In this study, we sought to characterize the cost-effectiveness of SelectMDx in a population of U.S. men with elevated PSA.
Reply by Authors We appreciate the comments acknowledging the PCM301 trial as the first published randomized study comparing PGA to active surveillance. We also agree that in carefully selected patients PGA reduces the aggregate treatment burden. This becomes a meaningful clinical benefit and an appropriate end point for clinical trials. After all, the benefit of AS itself is avoidance of the morbidity and the adverse impact on quality of life with RT. If PGA can further reduce the need for RT, it would provide a valuable supplement to active surveillance alone.
Editorial Comment These authors completed the first randomized, controlled trial demonstrating a benefit to partial prostate ablation in early stage prostate cancer, now with 4 years of followup. While we have traditionally looked for a benefit in cancer specific or overall survival before concluding that a cancer treatment is effective, this is hard to demonstrate even for prostatectomy for this disease. Thus, a reduction in the burden of care (ie radical whole gland prostate therapy) would also be beneficial as it reduces the cost and side effects of treatment.
Editorial Comment In the current issue Gill et al report long-term rates of RT in men enrolled in the PCM301 trial, which compared PGA by VTP and AS in men with low risk prostate cancer.1 They report that conversion rates to RT remained substantially lower at 2, 3 and 4 years of followup among men treated with VTP with the absolute risk reduction remaining constant at each year at 29%. Whether this demonstrates a delay in inevitable RT or whether some men will avoid RT altogether remains uncertain.
Erratum Volume 199, Number 5, Page 1182: The name of the sixth author in the string beneath the title is spelled Rashid Sayyid.
Erratum Volume 199, Number 5, Page 1136: Table 2, column 4, rows 6 and 7 should read Diarrhea +/or colitis… .
Reply by Authors Indeed, the relative value of manual evaluation by content experts compared to APMs remains to be seen. Our prior work suggests that APMs likely assess different aspects of surgery, given the statistically significant but low association between manually derived metrics and APMs (reference 12 in article). Moving forward, 1 form of assessment (manual or automated) will likely not replace the other but rather they will complement each other.
Editorial Comment Surgical education has moved away from process based curricula toward objective assessments of educational outcomes.1 This effort has increased emphasis on metrics of surgical skill acquisition as an essential component of surgical training programs. Several structured assessment tools have been validated in recent years which rely on manual evaluation (references 9 and 10 in article). While expert review provides the benchmark for skills assessment, because of its labor intensive nature and limitation of scale, there is ongoing work to understand the value of crowd assessed data and automated performance measures.
Editorial Comment Urine is an attractive noninvasive source of prostate cancer biomarkers. In this study Larsen et al performed droplet digital PCR to detect DNA methylation changes in GSTP1, APC, RASSF1A, PITX2 and C1orf114 in the urine of men undergoing prostate biopsy. The urinary biomarker panel achieved high accuracy for identifying patients with intermediate to high risk prostate cancer on biopsy when combined with clinical variables. The authors used microfiltration and repeat urine samples to overcome an important technical challenge related to the infrequent shedding of prostatic cells in urine.
Editorial Comment Postmenopausal women are at higher risk for bone loss and kidney stones. Epidemiological studies examining the associations between menopause and incident kidney stones are controversial. This study, which took advantage of the NHS II, provides valuable information showing an increased risk of kidney stones with natural and postoperatively induced menopause. An advantage is the presentation of kidney stone risk profiles in 658 participants with kidney stones before vs after menopause. This was important to explain the underlying pathophysiological mechanism of the development of kidney stones in this population.
Editorial Comment These authors present a comprehensive and yet concise systematic review on the inconsistencies of UTI definitions in intradetrusor onabotulinumtoxinA studies. They report that the UTI rate is often not reported and, when it is, the definition is highly variable. If the EAU and NIDRR definitions were applied, almost all studies would fail to meet the diagnostic criteria for UTI.
Editorial Comment A central question surrounding the practice of AS remains whether an interval of surveillance proves harmful to men who ultimately undergo curative surgery. Existing data suggest a limited negative effect of this delay, although evidence is neither consistent nor overwhelmingly conclusive (references 13 and 24 in article). The current study assessed 132 men who underwent RP after a median interval of 1.9 years on AS. The authors observed adverse surgical pathology in 39% of the cohort and a 10-year PSA relapse-free survival of 79.5% during longer term followup (median 10.9 years postoperatively, IQR 7.5–14.5).
Editorial Comment As we leave behind an era of physician directed outcomes and enter a new era focused on PROMs and patient subjective satisfaction this study by Cotter et al provides useful information when preoperatively counseling our patients awaiting anterior urethroplasty. As stated by the authors incontinence has been shown to affect postoperative satisfaction. Therefore, modulating patient expectations with regard to PMI is key, especially if the patient already experiences post-micturition dribbling. This study opens a door toward further evaluating the determinants of PMI, such as concomitant lower urinary tract symptoms.
Editorial Comment One of the greatest dilemmas in urethral reconstruction is how to approach stricture recurrences after urethroplasty. Redo urethroplasty is challenging. Dissection can be difficult in the scarred tissue and an already compromised blood supply decreases the chance of a successful outcome, making endoscopic management a tempting alternative. In smaller, single institutional cohorts good success with endoscopic management has been reported but variability in technique, prior repair and success rates often left room for doubt whether this would indeed be the preferred approach.
Editorial Comment This study by Sukumar et al is a retrospective multicenter review of the records of 53 patients who underwent endoscopic treatment for stricture recurrence after bulbar urethroplasty. In this cohort based on time to event analysis endoscopic treatment was successful in 41% of patients while the success rate after DVIU was higher than after urethral dilation (49% vs 10%).
Reply by Authors The choice of preoperative antibiotic will continue to be controversial. For each antibiotic there is an advantage and an inherent disadvantage, and, therefore, it will always be subject to critique. In this study nitrofurantoin was not tissue penetrating but only bactericidal.
Editorial Comment The authors have provided a level 1b, multicenter trial study and high quality publications on urolithiasis are desperately needed.1 Fatal infectious complications after PCNL should be prevented. Therefore, antibiotic prophylaxis is recommended but antibiotic overuse should be avoided in the era of increasing bacterial resistances. The noninferiority of short-term antibiotic application compared to 1-week pretreatment is an important finding confirming earlier reports.2 Nevertheless, the high sepsis rates of 12% and 14% question its cause and the choice of antibiotic.
Editorial Comment Unlike other diagnostic measures such as serological biomarkers, MRI is subject to several sources of variation. PI-RADSv2 is an effort to improve standardization to enhance clinical and scientific communication. Although the 5-tier system demonstrates a stepwise increase in the CDR, PI-RADS 4 lesions showed low CDRs in several studies. This is currently explained by the subjectivity of PI-RADS criteria (reference 10 in article).
Reply by Authors The added value of PSAD to PSA in the diagnostic algorithm of prostate cancer is not a new concept. However, the current study is among the recent few reports reexamining its diagnostic performance to detect clinically significant cancer and further refining a PSAD cutoff for this purpose. As discussed in the study these contemporary series show the optimum performance of PSAD when set to 0.1 ng/ml/cc or less.
Editorial Comment Avoiding unnecessary prostate biopsy is important to minimize the patient risk of complications such as infection and bleeding. Aminsharifi et al compared the performance of PSAD (PSA/volume) in 2,162 men with PSA 4 to 10 ng/ml undergoing initial biopsy. Based on a 96% negative predictive value the authors recommended a PSAD cutoff of less than 0.08 ng/ml/cc to determine the need for biopsy. Approximately 250 high grade cancers were caught and 5 were missed for every 1,000 men biopsied.
Editorial Comment Aminsharifi et al present their study on the predictive accuracy of PSAD for prostate cancer grade group 2 or greater. The study cohort consisted of 2,162 men with PSA in the diagnostic gray zone of 4 to 10 ng/ml, of whom 1,210 (56%) were African American. Interestingly the predictive accuracy of PSAD was independent of race and BMI. Stratification using a PSAD cutoff of 0.08 ng/ml/cc could have avoided 273 of 2,162 biopsies (13%), missing 48 of 622 grade group 1 cancers (8%) and 10 of 499 grade group 2 or greater cancers (2%).
This Month in Pediatric Urology Hypospadias represents one of the most common congenital anomalies encountered by pediatric urologists. Tremendous advances have occurred in the last few decades regarding surgical techniques but we still have only a vague understanding of the underlying risk factors. The exact genetic factors that create familial risk and the added impact of environmental endocrine disruptors and potential multi-generational epigenetic effects are still incompletely understood. We know that future male siblings of index patients with hypospadias are at increased risk but little information exists regarding the future risks when hypospadias is documented in the family history of previous generations.
Editorial Comment Bladder cancer has a marked male incidence of uncertain etiology.1 Mouse models show that androgen receptor and androgens convey an increased risk of bladder cancer after exposure to a carcinogen.2 Intriguingly an observational (not randomized) analysis of the PLCO (Prostate, Lung, Colorectal, and Ovarian) cancer screening trial showed a lower incidence of bladder cancer in men receiving finasteride (reference 5 in article).
Reply by Authors We appreciate the suggestion regarding further adjustments to visceral fat area and subcutaneous fat area with the addition of volumetric measurement (VAT and SAT). A single slice VFA/SFA measurement was chosen for our study since previously published data regarding increased risk of nephrolithiasis and visceral obesity were based on single slice measurements.7–9 When we conducted our analysis, no previous studies existed examining the relationship between volumetric abdominal adipose tissue measurements and nephrolithiasis risk.
Reply by Authors The comments by Temiz help to highlight the role of CSA as a predictor of post-nephron sparing renal function. It is known that the main variable affecting postoperative renal function is preserved renal volume.1 To date, there is no evidence that surgical approach (open, laparoscopic or robotic) has any effect on renal function after partial nephrectomy.2 Since the primary outcome of our study was renal function, we did not see any compelling reason to do a subgroup analysis based on surgical approach.
Re: Computerized Tomography Based Diagnosis of Visceral Obesity and Hepatic Steatosis is Associated with Low Urine pH We read this article with interest and propose further adjustments to the visceral fat area (VFA) and subcutaneous fat area (SFA) reported by the authors. For each computerized tomogram (CT) a single axial area measurement was obtained at L3-L4 in females regardless of body mass index (BMI), L2-L3 in males with BMI less than 40 kg/m2 and L1-L2 in males with BMI greater than 40 kg/m2 for visceral fat area and subcutaneous fat area. However, we maintain that a single axial area measurement was insufficient and inadequate to express visceral or subcutaneous fat area.
Reply by Authors Several years ago one of our fellows, Andrew Stec, who was a biomedical engineer, thought it would be helpful to obtain 3-D MRIs in all newborn exstrophy cases before and after closure. Our main interest at that time was distribution of the pelvic floor musculature before and after closure with and without pelvic osteotomy (reference 11 in article). Using this technology, along with new Brainlab technology intraoperative imaging, we have undertaken a U.S. Food and Drug Administration approved study that allows newborn and delayed closure under 3-D intraoperative guidance.
Editorial Comment The authors present a landmark and novel finding in the female patient with classic bladder exstrophy. Although the study is a retrospective analysis with a small sample size, the data and knowledge gained add vast amounts of information regarding the anatomy of female patients with bladder exstrophy. As with most good studies, this one generates more questions than answers. The immediate clinical value of this article should make anybody who performs closure of female bladder exstrophy cautious when dissecting the pelvic floor.
Reply by Authors We acknowledge that the missing information on serum levels of testosterone among the included TC survivors is a limitation of the current study. We recently performed a systematic review in which we found that radiotherapy, cisplatin based chemotherapy and more than 1 treatment line increase the risk of testosterone deficiency (total testosterone less than 10 nmol/l) compared to orchiectomy alone.1 However, to our knowledge it remains unknown whether mild biochemical testosterone deficiency causes symptoms such as decreased sexual desire and erectile dysfunction, and whether testosterone substitution should be offered to more than the approximately 5% of TC survivors reported in the current study.
Editorial Comment With 2,260 patients (a 60% response rate) and an impressive 17-year followup this study is the largest cohort and longest followup ever reported on sexual function among testis cancer survivors. This robust analysis from Bandak et al demonstrated that while the majority of survivors maintained normal erectile function, patients with testis cancer who underwent adjuvant treatment after orchiectomy were at higher risk for erectile dysfunction than those who underwent orchiectomy alone. These significant findings should guide patient discussions regarding the long-term effects of testis cancer treatment.
Editorial Comment The authors raise 3 important points. First, the familial incidence of hypospadias is underestimated and is more prevalent than previously reported (22.3%). Also, a positive family history is not correlated with type of hypospadias. Finally, genetic mutations are more frequently detected in familial cases.
This Month in Adult Urology The success with treatment of the overwhelming majority of patients with testis cancer is one of the most striking success stories in oncology. It also creates a situation in which survivors of the cancer are at risk for treatment related side effects for many decades. Although the potential impact on fertility has been studied extensively, other aspects of sexual function have not. Bandak et al (page 000) from Denmark evaluated 2,260 testis cancer survivors with a median 17-year followup using the International Index of Erectile Function questionnaire.
Finasteride—Nemesis of More Than 1 Urological Cancer? With the exponentially increasing costs of cancer therapies, there has been an increased emphasis on chemoprevention of disease. Emerging evidence demonstrates a potential role for the androgen axis in the development and progression of bladder cancer but the relationship has not been fully characterized.
Endoscopic Therapy for High Grade Vesicoureteral Reflux—First Line Therapy or Too Good to be True? In this issue of The Journal Friedmacher et al (page 650) present their results on endoscopic injection of dextranomer/hyaluronic acid (Dx/HA) copolymer in children with grade IV to V vesicoureteral reflux (VUR).1 The results are impressive: 100% of the children were successfully treated and not a single postoperative complication (other than rapidly resolving gross hematuria in 2 children) occurred during a median followup of 8.5 years. Taken at face value, these results seem to imply that we should be pushing families toward endoscopic management.
Reply by Authors We appreciate the comments on our study. There is clearly a road ahead and paths to tread to find the exact place of ultrasound SWE in the detection and phenotypic characterization of prostate cancer. There may be a place of combining this with MRI. However, publications in this area to date show promising results. What should be considered a discriminatory diagnostic cutoff level for benign and malignant lesions can be debated but there is some confidence that all studies in this area show differences in the relative stiffness estimates not only of cancer and noncancerous tissues but also of different Gleason grades (reference 12 in article).
Editorial Comment PCa detection remains a problem. Random TRUS biopsies have been the standard of care but they can often miss cancers and under grade the cancers that are identified. MRI has had success in identifying clinically significant PC and it may be helpful in active surveillance.1 SWE is a new technique that evaluates tissue stiffness.2 As most PCa is stiffer than normal prostate it can be detected by SWE and the stiffness appears to correlate with Gleason scores. However, benign prostatic nodules are also stiff, making evaluation of the central gland problematic with SWE.
Editorial Comment Imaging in localized prostate cancer is gaining importance. Specifically multiparametric MRI is frequently used for diagnosis, active surveillance, targeted biopsy and focal therapy. A major step in the acceptance and widespread use of MRI was the establishment of the standardized reporting system, PI-RADS® (Prostate Imaging-Reporting and Data System).1 Research on new techniques such as SWE should aim to establish comparable classification systems to catch up with MRI (reference 11 in article).
JU Forum The Journal of Urology® improves patient care by delivering to our readers the most current advances in the field, especially those with clinical implications and translation. Most often, this information is provided in the form of original scientific articles, review articles and guidelines. The Urological Survey section of The Journal broadens the focus to include pertinent papers published in other journals.
Editorial Comment In recent years there has been a dramatic increase in the number and availability of tools that assess risk following the diagnosis of PCa. These developments have occurred largely in 2 parallel tracks, including optimization of mpMRI, and discovery and validation of tissue based genomic tests (reference 4 in article).1 With little comparative study it has remained unclear whether these modalities are redundant or new prognostic value can be gleaned from additional testing (reference 17 in article).
Editorial Comment Genomic science has opened a new world of possibilities for understanding and treating men with prostate cancer. It enables for the first time ever the ability to directly assess the biological potential of the tumor in an individual and, thus, offers the promise of individualized treatment strategies based on biology rather than histology.
Editorial Comment This group examined a well characterized cohort of 183 patients who underwent IVC tumor thrombectomy and radical nephrectomy in a contemporary 10-year time frame at a highly experienced, high volume center. An important take home message is that symptomatic VTE develops postoperatively in a high fraction of patients, essentially more than 1 of 5, with VTE within 30 days after surgery in most of them. This is a much higher rate of VTE than has been observed for other complex genitourinary cancer surgeries, such as radical cystectomy.
Editorial Comment The incidence of VTE following major surgery is increased because of a pro-inflammatory hypercoagulable condition associated with anesthesia, surgical tissue manipulation and limited mobility during recovery. Cancer diagnosis also increases the risk of VTE and mortality is significantly higher in patients with cancer after a VTE diagnosis.1
Editorial Comment Among the many questions raised when prostate biopsy is to be MRI guided is what difference does it make if the MRI reveals more than 1 ROI? Patel et al help answer that question in the current study. It is not the number of ROIs but rather the degree of suspicion of any one of them, assessed in terms of the PI-RADS score, which portends the likelihood of serious cancer.
Editorial Comment The benefits of cytoreductive nephrectomy have been established based on the results of 2 prospective, randomized controlled trials that were done during the cytokine era (reference 2 in article).1 It is important to remember that most of the phase III trials which led to the approval of vascular endothelial growth factor receptor-tyrosine kinase inhibitors required initial CN prior to enrollment. Today initial CN continues to remain the recommended treatment in patients with mRCC in whom systemic therapy is anticipated (reference 1 in article).
Can we improve nonmuscle invasive bladder cancer guideline adherence with smarter risk stratification? Nonmuscle invasive bladder cancer (NMIBC) is one of the most complicated urological cancers to stage and treat accurately. Differing intravesical combinations among myriad clinical presentations gives NMIBC guidelines and their central component, risk stratification, greater importance. However, in a recent review adherence to some of the primary tenants of NMIBC treatment guidelines was sub-optimal. In the United States, Australia and Europe the use of restaging transurethral resection, bacillus Calmette-Guérin (BCG) therapy and a single perioperative instillation of chemotherapy ranged from 0.5% to 65%.
Reply by Authors We agree with the comments. As noted, there is growing awareness about other important side effects of ADT, which may be less familiar to urologists. These side effects include liver disease as well as important effects on cognition and even mood disorders (reference 3 in article).
Editorial Comment Using SEER data with Medicare linkage Gild et al assembled a large study cohort from which they advance the persuasive argument that ADT is associated with significant risks to liver health. In the absence of a significant prospective study SEER with Medicare linkage likely represents the best data source to study this question in an American population.
Editorial Comment NAFLD is the most common cause of liver disease in Western countries. Gild et al analyzed SEER-Medicare linkage observational data to determine the association between primary ADT and the potential subsequent development of NAFLD in patients with prostate cancer. While acknowledging the known limitations of administrative data, using restricting criteria for the cohort to overcome potential comorbidities and treatment related confounders, and applying using propensity score adjustments, the authors found that ADT is associated with a greater risk of liver disease, particularly NAFLD.
This Month in Pediatric Urology Vesicoureteral reflux (VUR) is one of the original conditions (along with hypospadias, cryptorchidism and hydronephrosis) that helped define the field of pediatric urology. There were a variety of open surgical options for VUR and one of the earliest concerns was trying to determine where these procedures fit into possible treatments versus observation on antibiotic prophylaxis and spontaneous resolution. To help answer this question, the International Reflux Study (IRS) was conducted, and the IRS grading system was created and remains an internationally accepted standard today.
Ethical Pitfalls When Estimating Life Expectancy for Patients with Prostate Cancer Mr. C is a 75-year-old man diagnosed with intermediate risk prostate cancer. The initial diagnosis was prompted by an increase in prostate specific antigen (PSA) from 2.6 to 3.6 ng/mL during 1 year of testosterone replacement therapy. The testosterone treatments were withheld. Magnetic resonance imaging (MRI) of the prostate identified 2 regions of interest. MRI-fusion biopsy diagnosed prostate cancer in 4 of 16 total cores. The patient was estimated to have a greater than 10-year life expectancy (he is an avid cyclist with a medical history significant for diverticulosis, osteoporosis, hypogonadism) and, consistent with guidelines, was offered definitive treatment (radiation or surgery) as well as surveillance after a detailed discussion.
Editorial Comment A complete response after multi-agent NAC is the target but it is achieved only a modest amount of the time (reference 2 in article). Negative transurethral bladder resection after NAC carries a high false-negative risk.1 Therefore, after NAC most patients should undergo consolidation with radical cystectomy or radiation.
The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy in Nonmuscle Invasive Bladder Carcinoma Clinical and pathological predictors of bladder carcinoma recurrence and progression are relatively well defined. However, there is a paucity of genetic data specifically on the association of single nucleotide polymorphisms in specific genes for predicting recurrence and progression following immunotherapy. The VDR gene was found to regulate the immunomodulatory effects of vitamin D and it enhances the innate immunity system. We evaluated 3 VDR single nucleotide polymorphisms and their predictive role on the response to immunotherapy.
The Association of Aspirin Use with Survival Following Radical Cystectomy Aspirin may have antineoplastic properties through the inhibition of inflammatory cytokines that regulate cell proliferation, angiogenesis and apoptosis. In patients with nonmuscle invasive bladder cancer aspirin use has been linked to a reduced risk of recurrence. We evaluated the association of aspirin with survival following radical cystectomy.
Risk of Radiation from Computerized Tomography Urography in the Evaluation of Asymptomatic Microscopic Hematuria The AUA (American Urological Association) guidelines for asymptomatic microscopic hematuria recommend that patients undergo computerized tomography urography, which is associated with high doses of ionizing radiation. To our knowledge the associated risk of secondary malignancy and mortality remains unknown. We modeled the risk of malignancy and associated mortality due to ionizing radiation from computerized tomography urography relative to the additional diagnostic benefit offered over renal ultrasound.
Re: Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer D. E. Spratt, J. Zhang, M. Santiago-Jiménez, R. T. Dess, J. W. Davis, R. B. Den, A. P. Dicker, C. J. Kane, A. Pollack, R. Stoyanova, F. Abdollah, A. E. Ross, A. Cole, E. Uchio, J. M. Randall, H. Nguyen, S. G. Zhao, R. Mehra, A. G. Glass, L. L. C. Lam, J. Chelliserry, M. du Plessis, V. Choeurng, M. Aranes, T. Kolisnik, J. Margrave, J. Alter, J. Jordan, C. Buerki, K. Yousefi, Z. Haddad, E. Davicioni, E. J. Trabulsi, S. Loeb, A. Tewari, P. R. Carroll, S. Weinmann, E. M. Schaeffer, E. A. Klein, R. J.
Reply by Authors We agree with the points regarding the continued (and successful) role of conservative management, the use of hematoma diameter as a continuous variable and the need for a clinically relevant nomogram to enhance clinical decision making. However, we disagree with the statement that ureteral stenting is “less relevant in relation to acute management of renal trauma.” Ureteral stenting represents a clinically relevant intervention for renal trauma, especially given that the AAST Organ Injury Scale specifies collecting system injury as an important factor stratifying renal trauma management.
Reply by Author There seems to be signaling that rezūm therapy at 3-year followup has lower rates of surgical repeat treatment than some of the other minimally invasive therapies for benign prostatic hyperplasia. In addition, I agree that the definition of repeat treatment is narrow. Most patients would suggest that if they are still on a medication years after therapy, they are still on “treatment.” Ultimately the experience in the urological community, governed partly by safety and efficacy as well as reimbursement, will determine the long-term future of any minimally invasive therapy.
Re: Perinephric Hematoma Size is Independently Associated with the Need for Urological Intervention in Multisystem Blunt Renal Trauma This article is a timely and apt report on imaging specifics associated with urological interventions after renal trauma. As more renal injuries are managed nonoperatively, the importance of injury specifics beyond those captured by the AAST (American Association for the Surgery of Trauma) Organ Injury Scale becomes more apparent. Of 328 patients eligible for this study 194 (59%) had high grade renal injuries and only 7 (4%) underwent nephrectomy. This rate is low compared to a recent multi-institutional study showing a nephrectomy rate of 13% at level 1 United States trauma centers.
This Month in Adult Urology Large administrative databases increasingly are the source of information used in medical publishing. Inevitably, the reliability of the findings depends on the accuracy of the analyzed data. Errors in decimal point placement on recorded prostate specific antigen (PSA) values used in SEER (Surveillance, Epidemiology, and End Results) data called into question some studies in which PSA was an important variable. Similar issues with the VACCR (Veterans Affairs Central Cancer Registry) are reported by Guo et al (page 541) from Stanford, California.
Editorial Comment This article identifies errors in PSA values in the VACCR, a massive national cancer registry, compared to the gold standard of the medical record values. The PSA value in more than 25% of patients was found to be misclassified when using registry data alone.
Reply by Authors Many researchers have highlighted that contemporary management of VUR should always be risk adapted and individualized based on the history of pyelonephritis and subsequent renal parenchymal damage, presence of bladder and bowel dysfunction, and parental preference.1,2 Although 30.5% of the patients in our series required more than 1 endoscopic treatment, only 10.4% had the need for a third injection to cure their high grade VUR. In fact, our resolution rate of 69.5% after a single injection of Dx/HA suggests that it makes sense to give a child with grade IV or V reflux at least 1 chance at endoscopic treatment before considering more invasive procedures.
Editorial Comment Surgical correction is often considered in children with persistent high grade VUR, renal parenchymal scarring and/or recurrent febrile urinary tract infections. Secondary to its minimally invasive nature, the frequency of endoscopic injection using Dx/HA increased rapidly in the early 2000s, with a subsequent decline in more recent years paralleling an overall decrease in VUR diagnosis and antireflux surgery.1,2 The literature in aggregate suggests that endoscopic injection is a relatively effective treatment for most VUR, while emphasizing the impact of grade and structural/functional bladder anomalies on ultimate success rates.
Evaluation of an Aggressive Prostate Biopsy Strategy in Men Younger than 50 Years of Age Longitudinal cohort studies and guidelines demonstrate that prostate specific antigen 1 ng/ml or greater in younger patients confer an increased risk of delayed prostate cancer death. At our institution we have used an aggressive biopsy strategy in younger patients with prostate specific antigen 1 ng/ml or greater. Our objective was to determine the proportion of detected cancer and specifically clinical significant cancer by this strategy.
Validation of Prostate Imaging-Reporting and Data System Version 2 for the Detection of Prostate Cancer The second version of the PI-RADS™ (Prostate Imaging Reporting and Data System) was introduced in 2015 to standardize the interpretation and reporting of prostate multiparametric magnetic resonance imaging. Recently low cancer detection rates were reported for PI-RADS version 2 category 4 lesions. Therefore the aim of the study was to evaluate the cancer detection rate of PI-RADS version 2 in a large prospective cohort.
Menopause and Risk of Kidney Stones Metabolic changes due to menopause may alter urine composition and kidney stone risk but results of prior work on this association have been mixed. We examined menopause and the risk of incident kidney stones, and changes in 24-hour urine composition in the NHS (Nurses’ Health Study) II.
Prostate Ablation Using High Intensity Focused Ultrasound: A Literature Review of the Potential Role for Patient Preference Information The FDA (Food and Drug Administration) recently allowed the marketing of 2 high intensity focused ultrasound devices for prostate tissue ablation indications after previous rejections for a prostate cancer indication due to insufficient data on clinical effectiveness or direct patient benefit. We reviewed the safety and effectiveness of high intensity focused ultrasound and knowledge regarding patient preferences, such as tolerance for adverse events associated with high intensity focused ultrasound ablation of tissue, in men with prostate cancer.
A Randomized Controlled Trial of Preoperative Prophylactic Antibiotics Prior to Percutaneous Nephrolithotomy in a Low Infectious Risk Population: A Report from the EDGE Consortium Single institution studies suggest a benefit of a week of preoperative antibiotics prior to percutaneous nephrolithotomy. These studies are limited by lower quality methodology, such as the inclusion of heterogeneous populations or nonstandard definitions of sepsis. The AUA (American Urological Association) Best Practice Statement recommends less than 24 hours of intravenous antibiotics but to our knowledge no other data exist on the duration or benefit of preoperative antibiotics. Using CONSORT (Consolidated Reporting of Trials) guidelines we sought to perform a rigorous multi-institutional trial to assess preoperative antibiotics in patients in whom percutaneous nephrolithotomy was planned and who were at low risk for infection.
Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer Androgen deprivation therapy is associated with the development of diabetes and metabolic syndrome. To our knowledge its effect on the development of nonalcoholic fatty liver disease, a condition which frequently co-occurs with metabolic syndrome and other subsequent liver conditions such as liver cirrhosis, hepatic necrosis or any liver disease, has not been investigated.
Predatory Publishing in Pediatric Urology In academic publishing predatory open access publishing is an exploitative business model that involves charging fees to authors without providing the editorial and publishing services associated with traditional journals (open access or not). Predatory publishing has become the buzzword in the last few years, as it permeates across the majority of medical and surgical subspecialties.
Editorial Comment Acknowledging the limitations of administrative data sets and the inability to demonstrate causality, this study still highlights several important aspects of acute care for children with nephrolithiasis. First, many children will initially present to nonpediatric hospitals, representing an opportunity and need for engaging adult urology and ED colleagues in the care of these children. In addition, although rates of urological consultation were low, urology consult was associated with decreased rates of ED revisits and use of CT.
When Clinical Trials Disagree In clinical and public health research randomized trials are indispensable for learning about what works. Trials can avoid many known biases of observational studies and provide a seemingly simple recipe for inference, ie if outcomes differ significantly between groups, the intervention works. However, trials have well-known limitations. Results may not generalize to other populations or other time horizons. Also, perplexingly, trials of similar interventions may yield conflicting results. Unfortunately, in these situations there is no universally accepted recipe for making sense of the evidence.
Editorial Comment This is an interesting article addressing a not too uncommon scenario in which a patient on required antiplatelet therapy is in need of surgical resection of a suspicious renal mass. While it makes complete sense intuitively that patients on clopidogrel can potentially have more bleeding complications, only 8 patients were on continued clopidogrel therapy. Therefore, some observations have to be viewed with caution. For example, the fact that those patients who remained on clopidogrel had longer operative times could be an incidental finding unless the operative notes dictated state that the increased operative time was due to intraoperative bleeding.
WITHDRAWN: Re: Managing a Pessary Business This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause.The full Elsevier Policy on Article Withdrawal can be found at (http://www.elsevier.com/locate/withdrawalpolicy).
Re: Loss of the Urothelial Differentiation Marker FOXA1 is Associated with High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer.
Information for Authors The Journal of Urology® contains 3 sections: Adult Urology, Pediatric Urology and Urological Survey. Original clinical and translational research studies will be considered for publication in the Adult and Pediatric Urology Sections. Translational research manuscripts must have a clear and proximate translation to patient care, and only preclinical scientific studies that have the direct potential to translate into new and improved standards of care will be reviewed.
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