Publications by authors named "Michael H Johnson"

77 Publications

Understanding Psychosocial and Sexual Health Concerns Among Women With Bladder Cancer Undergoing Radical Cystectomy.

Urology 2020 Aug 25. Epub 2020 Aug 25.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To better understand the physical and psychosocial components of female sexual dysfunction (FSD) among women undergoing radical cystectomy (RC) for bladder cancer (BCa).

Methods: We conducted semistructured individual interviews and a focus group with pre- and post-RC female patients and their partners regarding the impact of RC on sexual health and psychosocial wellbeing. Themes were inductively identified by 2 independent coders and subsequently organized into themes and subthemes using qualitative description and constant comparison.

Results: In the preoperative cohort, 6 women and 1 partner participated (50% contact rate, 75% participation rate). In the postoperative cohort, 16 women and 2 partners participated (61% contact rate, 64% participation rate). Major themes that emerged in interviews with both cohorts included concerns about changes to body image, the psychological impact of BCa diagnosis and treatment, concerns about the impact of RC on sexual function, and inadequacies in provider-led sexual health counseling. Participants varied in the importance they placed on sexual function, with factors such as age, relationship status, and oncologic concerns impacting prioritization, although both younger and older patients expressed a desire to retain the option of sexual function.

Conclusion: Female patients with BCa undergoing RC experience changes in body image, psychological distress, physical disruptions in sexual function, and inadequacies in sexual health counseling and education. Future efforts should be directed towards improving sexual health counseling and psychosocial support resources for women with BCa.
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http://dx.doi.org/10.1016/j.urology.2020.08.018DOI Listing
August 2020

Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.

Eur Urol 2021 Mar 17;79(3):364-371. Epub 2020 Aug 17.

The Greenberg Bladder Cancer Institute & James Buchanan Brady Urological Institute, Johns Hopkins Medicine, Baltimore, MD, USA.

Background: Standard of care for patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC) followed by consolidative therapy with either chemoradiation or radical cystectomy (RC). Some patients experience robust pathologic responses to NAC, and these have been reported to associate with somatic mutations in specific gene pathways including DNA damage response genes.

Objective: To evaluate the ability of post-NAC clinical restaging, with or without tumor sequencing, to predict final RC pathologic staging.

Design, Setting, And Participants: We reviewed our institutional review board-approved institutional database to identify patients with MIBC who underwent NAC followed by RC from 2003 to 2016. Following NAC prior to RC, cystoscopy was performed routinely, with resection of residual visible tumor and/or tumor base (transurethral resection [TUR]). For patients with pre-NAC tumor tissue available, tumor sequencing was performed. Outcome measurements and statistical analysis: Clinical restaging and tumor sequencing were evaluated for their ability to predict the final pathologic stage accurately at RC using chi-square or Fisher's exact test.

Results And Limitations: A total of 114 patients underwent restaging TUR following NAC and prior to RC. The diagnostic accuracy of post-NAC clinical restaging including TUR was poor, with 32% of patients being downstaged falsely when compared with their final RC pathology. Forty-nine patients had sequencing of pre-NAC tumor tissue, of whom 32 showed at least one mutation of interest. However, NAC responses and rates of false downstaging did not differ significantly according to tumor mutation status.

Conclusions: This study highlights the inaccuracy of post-NAC clinical restaging TUR with or without adjunctive tumor mutation analysis, to assess pathologic residual disease accurately. Caution must be taken when performing post-NAC restaging, especially when considering conservative management strategies such as active surveillance on this basis. Patient summary: Several groups are evaluating whether certain patients, whose bladder cancer responds well to upfront chemotherapy, may be able to forego cystectomy safely. We demonstrate that currently available staging tools and tumor DNA sequencing cannot identify such patients reliably and accurately.
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http://dx.doi.org/10.1016/j.eururo.2020.07.016DOI Listing
March 2021

High-dimensional Cytometry (ExCYT) and Mass Spectrometry of Myeloid Infiltrate in Clinically Localized Clear Cell Renal Cell Carcinoma Identifies Novel Potential Myeloid Targets for Immunotherapy.

Mol Cell Proteomics 2020 11 31;19(11):1850-1859. Epub 2020 Jul 31.

Bloomberg-Kimmel Institute for Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA. Electronic address:

Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC.
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http://dx.doi.org/10.1074/mcp.RA120.002049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664124PMC
November 2020

Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial.

Eur Urol 2020 09 19;78(3):360-368. Epub 2020 May 19.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation.

Objective: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort.

Design, Setting, And Participants: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018).

Intervention: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d.

Outcomes Measurements And Statistical Analysis: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed.

Results And Limitations: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection.

Conclusions: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection.

Patient Summary: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.
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http://dx.doi.org/10.1016/j.eururo.2020.05.001DOI Listing
September 2020

The association of broadband internet access with dermatology practitioners: An ecologic study.

J Am Acad Dermatol 2020 Dec 31;83(6):1767-1770. Epub 2020 Mar 31.

Department of Dermatology, Loma Linda University Health, Loma Linda, California.

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http://dx.doi.org/10.1016/j.jaad.2020.03.065DOI Listing
December 2020

Transcriptional profiling of tumor associated macrophages in human renal cell carcinoma reveals significant heterogeneity and opportunity for immunomodulation.

Am J Clin Exp Urol 2020 25;8(1):48-58. Epub 2020 Feb 25.

Bloomberg~Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine and The Sidney Kimmel Comprehensive Cancer Center Baltimore, MD 21231, USA.

Among the more notable immunotherapies are checkpoint inhibitors, which prevent suppressive signaling on T cells, thereby (re)activating them to kill tumor cells. Despite remarkable treatment responses to immune checkpoint blockade, with a subset of patients achieving complete responses, a large population have little-to-no response, dictating the necessity of further research in this field. Myeloid derived cells heavily infiltrate the tumor microenvironment (TME) of many cancers and are believed to have a number of potent anti-inflammatory effects. Here we use primary non-metastatic renal cell carcinoma to interrogate the gene expression profiles of M2-tumor associated macrophages (M2-TAMs). We performed Fluorescent Activated Cell (FACS) sorting on monocytes from the peripheral blood and tumors of fresh clear cell renal cell carcinoma (ccRCC) samples obtained after patients underwent a partial (7 patients-87.5%) or radical (1 patient-12.5%) nephrectomy. We then utilized NanoString gene expression profiling to show that TAMs express a heterogeneous transcriptional profile that does not cleanly fit into the traditional M1-M2 TAM paradigm. We identified expression of M1 associated costimulatory molecules, a multitude of diverse chemokines, canonical M2 associated molecules, as well as factors involved in the Complement system and checkpoint receptors. Our data are in agreement with other published literature investigating TAMs in various non-ccRCC TMEs, and support the growing literature concerning expression of Complement factors and checkpoint receptors on TAMs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076295PMC
February 2020

The incidence, predictors, and survival of disappearing small renal masses on active surveillance.

Urol Oncol 2020 02 6;38(2):42.e1-42.e6. Epub 2019 Nov 6.

James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, MD.

Objective: To evaluate the incidence, predictors, and survival for those small renal masses (SRM, solid mass ≤4 cm suspicious for a clinical T1a renal cell carcinoma) that disappear on imaging while undergoing active surveillance (AS).

Subjects/patients And Methods: The Delayed Intervention and Surveillance for SRM registry prospectively enrolled 739 patients with SRMs. Patients having at least 1 image showing no lesion were considered to have a "disappearing" SRM. Logistic regression assessed predictors of having a disappearing SRM and Kaplan-Meier estimates illustrated relative survival.

Results: Of 374 patients enrolled in AS, 22 (5.9%) experienced a disappearing SRM. Mean time to tumor disappearance was 2.0 years (SD = 1.9) and 50.0% reappeared on subsequent CT imaging. SRM disappearance, most commonly encountered on ultrasound imaging surveillance, was independently associated with tumors <1 cm on multivariable analysis (OR = 10.6 (95% CI: 1.1-100.3), P = 0.04). Furthermore, patients with disappearing SRMs were healthier than other patients on AS with no compromise in overall survival during follow-up (5-year survival = 100% vs. 73.2%, P = 0.06).

Conclusions: Approximately 5% of SRM on AS will disappear during follow-up on surveillance imaging. Most of these represent artifacts of heterogeneous imaging modalities, including ultrasound, and the SRM will reappear on subsequent imaging. Given the indolent nature of these lesions, disappearance events do not require reflex repeat imaging and patients should continue AS with their original surveillance schedule intact. A smaller percentage of patients undergoing AS for a SRM may have a mass the permanently disappears.
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http://dx.doi.org/10.1016/j.urolonc.2019.10.005DOI Listing
February 2020

Urothelial carcinoma within the prostatic utricle of an adult with hypospadias and Fanconi anemia.

Urol Case Rep 2020 Jan 15;28:101043. Epub 2019 Oct 15.

The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, 600 N. Wolfe. St., Baltimore, MD, 21287, USA.

Prostatic utricles are rare in the general population and are often otherwise unremarkable anatomic variants. These structures are contiguous with the prostatic urethra and are nevertheless susceptible to urothelial carcinoma. This case report discusses the first reported patient with Fanconi anemia with urothelial carcinoma within an enlarged prostatic utricle.
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http://dx.doi.org/10.1016/j.eucr.2019.101043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818153PMC
January 2020

Circulating Tumor Cell and Circulating Tumor DNA Assays Reveal Complementary Information for Patients with Metastatic Urothelial Cancer.

Eur Urol Oncol 2019 Sep 25. Epub 2019 Sep 25.

The James Buchanan Brady Urological Institute and Greenberg Bladder Cancer Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Despite considerable advances in the management of urothelial carcinoma (UC), better risk stratification and enhanced detection of minimal residual disease are still urgent priorities to prolong survival while avoiding the morbidity of overtreatment. Circulating tumor cells and DNA (CTCs, ctDNA) are two biologically distinct "liquid biopsies" that may potentially address this need, although they have been understudied in UC to date and their relative utility is unknown. To this end, matched CTC and ctDNA samples were collected for a head-to-head comparison in a pilot study of 16 patients with metastatic UC. CTCs were defined as cytokeratin- and/or EpCAM-positive using the RareCyte direct imaging platform. ctDNA was assayed using the PlasmaSelect64 probe-capture assay. 75% of patients had detectable CTCs, and 73% had detectable somatic mutations, with no correlation between CTC count and ctDNA. 91% of patients had tissue confirmation of at least one plasma mutation and, importantly, several clinically actionable mutations were detected in plasma that were not found in the matching tumor. A ctDNA fraction of >2% was significantly associated with worse overall survival (p=0.039) whereas CTC detection was not (p=0.46). Notably, using a predefined gene panel for ctDNA detection had a high but not complete detection rate in metastatic UC, similar to what has been described for a custom tissue-personalized assay approach. In sum, both liquid biopsies show promise in UC and deserve further investigation. PATIENT SUMMARY: New "liquid biopsy" blood tests are emerging for urothelial cancer aimed at early detection and avoiding overtreatment. Our results suggest that two such tests provide complementary information: circulating tumor cells may be best for studying the biological features of a person's cancer, whereas circulating tumor DNA may be better for early detection.
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http://dx.doi.org/10.1016/j.euo.2019.08.004DOI Listing
September 2019

Stage-specific conditional survival in renal cell carcinoma after nephrectomy.

Urol Oncol 2020 01 12;38(1):6.e1-6.e7. Epub 2019 Sep 12.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: Conditional survival (CS) represents the probability that a cancer patient will survive some additional number of years, given that the patient has already survived for a certain period of time. CS estimates, therefore, serve as better measures of survival probability compared to standard estimates as they incorporate patient survivorship. Stage-specific CS has not been widely investigated in the context of renal cell carcinoma (RCC) after nephrectomy. We aimed to examine this phenomenon.

Materials And Methods: We analyzed retrospective data on a population-based cohort of 87,225 surgically-treated RCC patients extracted from the Surveillance, Epidemiology, and End Results database (2004-2015) and on a similar validation cohort of 1,642 patients from our institution (1995-2015). 5-year cancer-specific CS estimates stratified by stage were obtained using the Kaplan-Meier method. Multivariable Cox regression analyses were performed to evaluate the possible variation in risk of cancer-specific mortality by stage at nephrectomy and with increasing postoperative survivorship.

Results: 5-year cancer-specific survival rates at time of nephrectomy for stage I, II, III, and IV patients in the population-based cohort were 97.4%, 89.9%, 77.9%, and 26.7%, respectively. Improvement in 5-year CS was mainly observed in surviving patients with advanced-stage disease; given 1, 2, 3, 4, and 5 years of survivorship after nephrectomy, the subsequent 5-year cancer-specific survival rates were, respectively, 79.3% (+1.8% increase over previous survival probability), 81.3% (+2.5%), 83.3% (+2.5%), 84.3% (+1.2%), and 85.1% (+1.0%) for stage III, and 34.6% (+29.6%), 42.5% (+22.8%), 49.0% (+15.3%), 55.7% (+13.7%), and 58.6% (+5.2%) for stage IV. A similar trend was established in the validation cohort. Findings were confirmed upon multivariable analyses.

Conclusions: CS after nephrectomy for RCC varies dramatically by stage of disease. Gains in CS over time occur primarily among patients with advanced-stage disease. Stage-specific CS estimates can help urologists better plan postoperative surveillance for RCC patients.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.011DOI Listing
January 2020

Surgical removal of renal tumors with low metastatic potential based on clinical radiographic size: A systematic review of the literature.

Urol Oncol 2019 08 13;37(8):519-524. Epub 2019 Jun 13.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Introduction: Many patients with small renal masses (SRM) undergo surgical resection of benign and potentially indolent renal masses. We review the available literature to quantify the proportion of renal tumors that are low-risk based on clinical radiographic size, and quantify the number of low-risk masses surgically removed in the United States.

Methods: We systematically reviewed the literature for studies including pathologic findings after excision of renal masses. Inclusion criteria required studies capture both benign and malignant histology at surgical pathology, tumor grade, and stratification by radiographic tumor size. We queried our institutional database using the same parameters. Meta-analysis results were applied to SEER incidence and management data for renal masses. Very-low-risk tumors were defined as benign or grade 1 cT1a, and low-risk tumors as benign, grade 1, or grade 2 cT1a.

Results: A total of 733 titles were reviewed at title screening with 6 full text articles and our institutional database included for meta-analysis. Pooled estimates of benign, very-low-risk, and low-risk tumors were stratified by tumor size: ≤2 cm (25.5%, 40.1%, and 89.3%), 2 to 3 cm (21.2%, 34.1%, and 84.5%), 3 to 4 cm (16.1%, 26.6%, and 77.1%), 4 to 6 cm (11.9%, 23.8%, and 66.4%), and >6 cm (7.2%, 12.6%, and 50.3%). An estimated 3,300 benign, 5,400 very-low-risk, and 13,600 low-risk SRMs were resected in 2014 in the United States.

Conclusion: A substantial portion of patients with SRM are undergoing surgical excision despite harboring tumors of low metastatic potential. The rate of high-grade histology increased with increasing clinical radiographic size, which can be used in counseling and decision-making regarding placement on active surveillance. The number of low-risk SRM removed annually in the United States increased from 8,500 in 2000 to 13,600 in 2014 with stabilization in recent years.
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http://dx.doi.org/10.1016/j.urolonc.2019.05.013DOI Listing
August 2019

Selecting Patients with Small Renal Masses for Active Surveillance: A Domain Based Score from a Prospective Cohort Study.

J Urol 2019 05;201(5):886-892

The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine , Baltimore , Maryland.

Purpose: We sought to identify predictors of active surveillance in a prospective cohort study of patients with a small renal mass demonstrating favorable outcomes. We generated a summary score to discriminate patients selected for active surveillance or primary intervention.

Materials And Methods: We analyzed the records of 751 patients from 2009 to 2018 who were enrolled in the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry to compare active surveillance and primary intervention in the domains of demographics, tumor characteristics, comorbidity and patient reported quality of life. Regression models were created to assess univariable and multivariable model discrimination by the AUC and quality by the AIC (Akaike information criterion). The DISSRM score was based on the most predictive combination of variables and validated for its association with overall survival by Kaplan-Meier survival curves and a Cox proportional hazards regression model.

Results: Of the patients 410 (55%) elected active surveillance and 341 (45%) elected primary intervention. Of the domains patient age, the Charlson comorbidity index, tumor diameter and the SF-12® Physical Component Score had the greatest discrimination for clinical selection into active surveillance. These domains made up the DISSRM score (AUC 0.801). The maximum DISSRM score was 7. The average score for active surveillance was 4.19 (median 4, IQR 2-6) and 72% of scores were 4 or greater. The average score for primary intervention was 3.03 (median 3, IQR 1-5) and 63% of scores were 3 or less. A higher DISSRM score was associated with worse overall survival, for example a score of 6-7 had a HR of 10.45 (95% CI 1.25-87.49, p = 0.03).

Conclusions: The DISSRM score represents a measure of oncologic and competing risks of death in various important domains in patients with a small renal mass. It could be used to guide the management selection. Patients with intermediate scores that express illness uncertainty may require additional workup, such as confirmatory biopsy, to reach a treatment decision.
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http://dx.doi.org/10.1097/JU.0000000000000033DOI Listing
May 2019

Use of delayed intervention for small renal masses initially managed with active surveillance.

Urol Oncol 2019 01 13;37(1):18-25. Epub 2018 Nov 13.

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD.

Introduction: A number of patients who elect active surveillance of their small renal masses (≤4 cm) subsequently pursue delayed intervention (DI). The indications, timing, and rates of DI have not been well determined prospectively.

Materials And Methods: Data from Delayed Intervention and Surveillance for Small Renal Masses, a prospective, multi-institutional registry was utilized to evaluate factors associated with DI between 2009 and 2018.

Results: Of 371 patients enrolled in AS, 46 (12.4%) pursued DI. Patients who pursued DI spent a median 12 months on surveillance (interquartile range 5.5-23.6), had better functional status (P < 0.01), and had greater median growth rate vs. those who remained on surveillance (0.38 vs. 0.05, P < 0.001). Indications for intervention included growth rate >0.5 cm/y for 23 (50%) patients, patient preference for 22 (47.8%) patients, and qualification for renal transplant in 1 (2.2%) patient. Thirty-two patients (69.6%) underwent nephron-sparing surgery, 5 (10.9%) underwent radical nephrectomy, and 9 (19.6%) underwent percutaneous cryoablation. Renal mass biopsy was utilized in 37 (11.4%) and 15 (32.7%) patients in the AS and DI arms, respectively (P = 0.04). No patients experienced metastatic progression or died of kidney cancer.

Conclusions: As nearly 50% of patients pursue DI secondary to anxiety in the absence of clinical progression, comprehensive counseling is essential to determine if patients are suitable for a surveillance protocol. AS remains a safe initial management option for many patients but may not be a durable strategy for patients who are acceptable surgical candidates with an extended life expectancy. DI does not compromise oncologic outcomes or limit treatment options.
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http://dx.doi.org/10.1016/j.urolonc.2018.10.001DOI Listing
January 2019

Patient Decision-making and Predictors of Genital Satisfaction Associated With Testicular Prostheses After Radical Orchiectomy: A Questionnaire-based Study of Men With Germ Cell Tumors of the Testicle.

Urology 2019 02 28;124:276-281. Epub 2018 Oct 28.

James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To better understand patient decision-making and genital satisfaction associated with postorchiectomy testicular prosthesis (TP) implantation in patients with germ cell tumors of the testicle.

Materials And Methods: An electronic survey to assess TP decision-making and genital satisfaction was distributed to patients via an institutional database (n = 70) and social media outlets (n = 167). Statistical analyses were performed using chi-square tests for categorical variables, Wilcoxon-Mann-Whitney tests for continuous variables, and multivariate regression analyses to identify independent predictors of receiving a prosthesis, genital satisfaction, and prosthesis satisfaction.

Results: 24.9% of respondents elected to receive a TP, but 42% of men without a prosthesis reported never being offered one. Identifying as a heterosexual man (2.86) and receiving a TP (odds ratio = 3.29) were both positive predictors of overall genital satisfaction. Having the orchiectomy performed at an academic institution (odds ratio = 2.87) was a positive predictor of testicular prosthesis TP placement. 89.8% of TP recipients were satisfied with the look of their prosthetic, but only 59.3% of respondents were satisfied with prosthetic feel.

Conclusion: There are high levels of genital satisfaction in those who elect to receive a TP postorchiectomy. Associations between TP placement, genital satisfaction, and sexuality merit further investigation. Our results also indicate that patients who pursue an orchiectomy at an academic institution are more likely to receive a TP. The use of social media to recruit study participants in urology should be explored further.
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http://dx.doi.org/10.1016/j.urology.2018.09.021DOI Listing
February 2019

Comparative effectiveness of management options for patients with small renal masses: a prospective cohort study.

BJU Int 2019 01 9;123(1):42-50. Epub 2018 Aug 9.

Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: To explore the comparative effectiveness of partial nephrectomy (PN), radical nephrectomy (RN), ablative therapies (ablation) and active surveillance (AS) for small renal masses (SRMs; tumour diameter ≤4.0 cm) in the domains of survival, renal function and quality of life (QoL) using the prospectively maintained Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry.

Patients And Methods: Estimated glomerular filtration rate (eGFR) was calculated from creatinine values to determine renal function. QoL was measured using the Short Form 12 (SF-12) questionnaire. The Kaplan-Meier method and Cox proportional hazards regression were used for survival analysis. The mixed-effects model was used for renal function and QoL analysis.

Results: Of 638 patients, 231 (36.2%) chose PN, 41 (6.4%) RN, 27 (4.2%) ablation and 339 (53.1%) AS. Cancer-specific survival at 7 years was 98.8% in PN patients and 100% in all other groups. Overall survival (OS) at 7 years was 87.9%, 90.2%, 83.5% and 66.1% in PN, RN, ablation and AS patients, respectively. The OS rate was significantly worse in the AS group than other groups and likely attributable to older age and increased comorbidities. The eGFR was lowest in RN patients but comparable in all other groups. QoL was lowest in AS patients due to lower physical health scores, but mental health scores were similar in all groups.

Conclusions: With excellent oncological outcomes in all groups, nephron-sparing approaches, like PN and ablation, are preferred over RN when intervention is indicated for SRMs. AS is a reasonable option for select patients, given the comparable oncological and mental health outcomes.
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http://dx.doi.org/10.1111/bju.14490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6301094PMC
January 2019

Management of advanced adenocarcinoma in Indiana Pouch urinary diversion.

Urol Case Rep 2018 Mar 11;17:53-55. Epub 2018 Jan 11.

The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, 1800 Orleans Street, Marburg 420, Baltimore, MD 21287, USA.

Adenocarcinoma is a rare finding following urinary diversion with gastrointestinal segments. This report describes an 80-year-old woman with a history of bladder cancer who subsequently developed a pT4 adenocarcinoma 8 years following her radical cystectomy and Indiana Pouch continent urinary diversion. An en bloc resection of the pouch and affected small bowel was performed and the patient underwent conversion to an ileal conduit diversion. We use this case to highlight a mechanism for possible pathogenesis and the management of adenocarcinoma in urinary diversions including the need for regular surveillance and the surgical approach.
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http://dx.doi.org/10.1016/j.eucr.2018.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782398PMC
March 2018

Comparison of Pathological Stage in Patients Treated with and without Neoadjuvant Chemotherapy for High Risk Upper Tract Urothelial Carcinoma.

J Urol 2018 07 4;200(1):68-73. Epub 2018 Jan 4.

Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; The Greenberg Bladder Cancer Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Purpose: High risk upper tract urothelial carcinoma has been associated with poor survival outcomes. Limited retrospective data support neoadjuvant chemotherapy prior to radical nephroureterectomy. To validate prior findings we evaluated differences in the pathological stage distribution in patients with high risk upper tract urothelial carcinoma based on the administration of neoadjuvant chemotherapy before radical nephroureterectomy.

Materials And Methods: We retrospectively analyzed the records of 240 patients with upper tract urothelial carcinoma at The Johns Hopkins Hospital from 2003 to 2017. Patients with biopsy proven high grade disease and a visible lesion on cross-sectional imaging were offered neoadjuvant chemotherapy prior to radical nephroureterectomy. A control group of a time matched cohort of patients with biopsy proven high grade disease underwent extirpative surgery alone. The chi-square and Fisher exact tests were used to evaluate clinical and pathological variables between the cohorts.

Results: There were 32 patients in the study group and 208 in the control group. Significantly lower pathological stage was noted in the study group than in the control group (p <0.001). Significantly fewer patients with pT2 disease or higher were treated with neoadjuvant chemotherapy (37.5% vs 59.6%, p = 0.02). There was a 46.5% reduction in the prevalence of pT3 disease or higher in study group patients without clinically node positive or low volume metastatic disease (25.9% vs 48.4%, p = 0.04). A 9.4% complete remission rate was observed in patients who underwent neoadjuvant chemotherapy.

Conclusions: Patients with high risk upper tract urothelial carcinoma treated with neoadjuvant chemotherapy were noted to have a lower pathological stage distribution than patients treated with radical nephroureterectomy alone.
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http://dx.doi.org/10.1016/j.juro.2017.12.054DOI Listing
July 2018

Selecting Patients with Small Renal Masses for Active Surveillance.

Anticancer Agents Med Chem 2018 ;18(7):931-939

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins Hospital, Baltimore, 21287 MD, United States.

The incidentally discovered, clinically-localized, small renal mass (clinical stage T1aN0M0, ≤4cm) is the most commonly diagnosed entity in Renal Cell Carcinoma (RCC) - now accounting for at least 40% of newly diagnosed renal tumors. Given the above argument, Active Surveillance (AS) has emerged as a viable management strategy for SRM. This review will examine and discuss the existing literature regarding selection criteria for AS. AS of clinical T1a renal masses is emerging as a safe and effective management strategy in selected patients, yet appropriate patient selection and counseling remains an area of great interest. Long-term clinical outcomes are just beginning to be reported, thus much of the supporting evidence on AS and patient selection is based on retrospective data of heterogeneous quality. Nevertheless, there are certain conclusions that can be drawn, despite these current limitations. Appropriate selection of candidates should include a comprehensive evaluation of competing health risks, tumor characteristics, and patient preferences.
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http://dx.doi.org/10.2174/1871520617666171113152225DOI Listing
June 2019

Low levels of PSMA expression limit the utility of F-DCFPyL PET/CT for imaging urothelial carcinoma.

Ann Nucl Med 2018 Jan 24;32(1):69-74. Epub 2017 Oct 24.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To explore the clinical utility of PSMA-targeted F-DCFPyL PET/CT in patients with metastatic urothelial carcinoma.

Methods: Three patients with metastatic urothelial carcinoma were imaged with F-DCFPyL PET/CT. All lesions with perceptible radiotracer uptake above background were considered positive. Maximum standardized uptake values were recorded for each detected lesion and findings on F-DCFPyL PET/CT were compared to those on conventional imaging studies. To further explore PSMA as a molecular target of urothelial carcinoma, RNA-sequencing data from The Cancer Genome Atlas were used to compare the relative expression of PSMA among cases of bladder cancer, prostate cancer, and clear cell renal cell carcinoma. Additionally, immunohistochemical staining for PSMA was performed on a biopsy specimen from one of the imaged patients.

Results: F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma, albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data revealed that bladder cancer had significantly lower levels of PSMA expression than both prostate cancer and clear cell renal cell carcinoma. Consistent with this observation, immunohistochemical staining of tissue from one of the imaged patients demonstrated a low level of neovascularization and nearly absent PSMA expression.

Conclusion: The relatively scant expression of PSMA by urothelial carcinoma likely limits the utility of PSMA-targeted PET imaging of this malignancy. Future research efforts should focus on the development of other molecularly targeted imaging agents for urothelial carcinoma.
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http://dx.doi.org/10.1007/s12149-017-1216-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881395PMC
January 2018

Hospital Charges and Length of Stay Following Radical Cystectomy in the Enhanced Recovery After Surgery Era.

Urology 2018 Jan 13;111:86-91. Epub 2017 Oct 13.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To report our center's experience with enhanced recovery after surgery (ERAS) pathway for radical cystectomy (RC), specifically evaluating complications, LOS, 30- and 90-day readmissions, and hospital charges. Pathways of this type have been shown to decrease the length of stay (LOS) and postoperative ileus. However, concerns persist that ERAS is costly and increases readmissions. To date, limited studies have evaluated these concerns.

Materials And Methods: Our ERAS protocol was implemented for RC in December 2015. Outcomes in ERAS patients were compared with those in RC patients from the time period before ERAS. Patients were excluded if they underwent concomitant nephroureterectomy.

Results: Fifty-six consecutive ERAS patients were compared with 54 pre-ERAS patients. The median charge for index hospitalization was $31,090 in the ERAS group and $35,489 in the pre-ERAS group (P = .036). The median LOS was 5.0 days in the ERAS group and 8.5 days in the pre-ERAS group (P = < .001). The pre-ERAS group had a significantly increased use of nasogastric tube (13.8% vs 30.0%) and parenteral nutrition (6.9% vs 20.4%). The overall complication rate (including infectious, renal, deep vein thrombosis and pulmonary embolism, myocardial infarction and stroke, and respiratory and gastrointestinal-related complications) was similar between the 2 groups (51.7% in the ERAS group and 62.0% in the pre-ERAS group, P = .28). Thirty- and 90-day readmissions also remained similar (19.0% vs 14.8%, P = .55, and 31.0% vs 27.7%, P = .64). The most common readmission reason was infection, specifically urinary tract infection.

Conclusion: Implementation of the ERAS pathway at our center resulted in significantly reduced LOS and total hospital charge, with comparable rates of complication and readmission, highlighting the need for ERAS pathways in patients undergoing RC.
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http://dx.doi.org/10.1016/j.urology.2017.09.010DOI Listing
January 2018

Multiple growth periods predict unfavourable pathology in patients with small renal masses.

BJU Int 2018 05 1;121(5):732-736. Epub 2017 Nov 1.

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To use the number of positive growth periods as a characterization of the growth of small renal masses in order to determine potential predictors of malignancy.

Patients And Methods: Patients who underwent axial imaging at multiple time points prior to surgical resection for a small renal mass were queried. Patients were categorized based on their pathological tumour grade and stage: favourable (benign, chromophobe and low-grade pT1-2 renal cell carcinoma [RCC]) vs unfavourable (high-grade of any stage and low-grade pT3-4 RCC). A positive growth period was counted each time the difference in greatest tumour diameters between two images was positive. The Cochran-Armitage trend test and Somers' D association were used to determine if the number of positive growth periods was correlated with unfavourable pathology.

Results: Of the 124 patients, 86 (69.4%) had favourable pathology and 38 (30.6%) had unfavourable pathology. Those who had favourable pathology were younger than those who had unfavourable pathology: median (interquartile range [IQR]) 61.0 (52.2-66.0) vs 68.5 (61.5-77.0); P < 0.001. The overall growth rate was higher in the unfavourable group, but was not statistically significant: mean (sd) 0.7 (1.7) vs 1.6 (2.8) cm/year; P = 0.07. There was a significant trend difference in the number of positive growth periods between favourability groups (P = 0.02). An association between increased number of positive growth periods and unfavourable pathology was observed: 0.15 (95% confidence interval 0.02, 0.29). The ratios of favourable to unfavourable pathology were 1.8, 1.0, 0.66, 0.59 and 0 as the number of positive growth periods increased from 0 to 4, respectively.

Conclusion: While overall growth rate was not predictive of pathology favourability, there was a positive association between the number of positive growth periods and unfavourable pathology. The number of positive growth periods may be a potential parameter for malignant potential in patients undergoing active surveillance for small renal masses.
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http://dx.doi.org/10.1111/bju.14051DOI Listing
May 2018

Incidence of T3a up-staging and survival after partial nephrectomy: Size-stratified rates and implications for prognosis.

Urol Oncol 2018 01 29;36(1):12.e7-12.e13. Epub 2017 Sep 29.

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD.

Background: The use of partial nephrectomy (PN) to treat renal cell carcinoma has grown to include larger, more complex tumors. Such tumors are more likely to be up-staged to pT3a and generate controversy regarding the oncologic safety of PN. We aimed to estimate the proportion of patients up-staged to T3a disease after PN, stratified by clinical stage, and characterize their survival.

Methods: From 1998 to 2013, pT1-pT3aN0M0 kidney cancer patients undergoing PN or radical nephrectomy (RN) were identified from the Surveillance Epidemiology and End Results registries. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease to stratified, up-staged pT3a patients undergoing PN. Also, we compared PN patients with up-staged pT3a disease to RN patients with pT3a disease.

Results: From the 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a was 4.2%, 9.5%, and 19.5% for cT1a, cT1b, and cT2, respectively. OS was worse for tumors up-staged from cT1a to pT3a, but not for cT1b or cT2 tumors. Up-staged pT3a tumors across all stage strata demonstrated worse CSS, with worse survival for larger tumors. Analysis revealed no difference in OS or CSS for up-staged pT3a PN patients compared to pT3a RN patients.

Conclusions: A greater proportion of patients experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse CSS across all clinical tumor stages after PN. However, our results do not demonstrate that patients up-staged after PN have compromised oncologic outcomes compared to all-comers with pT3a disease receiving RN.
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http://dx.doi.org/10.1016/j.urolonc.2017.09.005DOI Listing
January 2018

Growth Kinetics of Small Renal Masses on Active Surveillance: Variability and Results from the DISSRM Registry.

J Urol 2018 03 23;199(3):641-648. Epub 2017 Sep 23.

The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital (ACU, HDP, RA, MAG, MHJ, HG, MFR, BJT, MEA, PMP), Baltimore, Maryland; Division of Urology, Beth Israel Deaconess Medical Center (PC, AAW), Boston, Massachusetts; Department of Urology, Columbia University Medical Center (JMM), New York, New York.

Purpose: Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi-institutional study of patients with small renal masses.

Materials And Methods: Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi-institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates.

Results: We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died.

Conclusions: Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates.
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http://dx.doi.org/10.1016/j.juro.2017.09.087DOI Listing
March 2018

Bladder melanosis with concurrent urothelial carcinoma.

Urol Case Rep 2017 Nov 12;15:30-32. Epub 2017 Sep 12.

Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.

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http://dx.doi.org/10.1016/j.eucr.2017.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596324PMC
November 2017

Improving antibiotic prophylaxis in gastrointestinal surgery patients: A quality improvement project.

Ann Med Surg (Lond) 2017 Aug 15;20:6-12. Epub 2017 Jun 15.

Johns Hopkins Hospital, Baltimore, MD, USA.

Background: A surgical site infection (SSI) is a frequent complication following gastrointestinal surgery, but the careful selection and administration of prophylactic antibiotics can reduce the risk. The aim of this study was to develop a package of interventions that could be used to improve surgical antibiotic prophylaxis (SAP) at our institution.

Methods: A pre-post quality improvement project at a private hospital in Saudi Arabia was conducted between January 2014 until July 2016. A multidisciplinary team was assembled to identify and overcome barriers that were responsible for patients receiving suboptimal antibiotic prophylaxis. Patients were included if they had undergone surgery on their appendix, colon, rectum, or small intestine. Compliance with use of an adapted order form, as well as appropriate antibiotic selection, dosing, timing, and timing of re-dosing, were measured. Data on the rates of SSI before and after the intervention were also obtained.

Results: Of the 269 patients included in the study, 161 (61.5%) had appendix surgery, 86 (32.8%) had colorectal surgery, and 15 (5.7%) had small bowel surgery. The surgery was performed laparoscopically in 218 (83.5%) of patients. Utilization of the adapted order form increased from 1.8% to 92.0% following the intervention (p < 0.001). Compliance with a bundle of appropriate antibiotic selection, dosing and timing improved from 47.3% to 82.2% after the intervention (p < 0.001). Additionally, there was a non-statistically significant reduction in SSI rate (9.1% vs 5.1%; p = 0.27).

Conclusions: Our quality improvement intervention was successful in improving SAP for patients undergoing gastrointestinal surgery at our institution.
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http://dx.doi.org/10.1016/j.amsu.2017.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480815PMC
August 2017

Renal Functional Outcomes after Surgery, Ablation, and Active Surveillance of Localized Renal Tumors: A Systematic Review and Meta-Analysis.

Clin J Am Soc Nephrol 2017 Jul 8;12(7):1057-1069. Epub 2017 May 8.

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Departments of.

Background And Objectives: Management strategies for localized renal masses suspicious for renal cell carcinoma include radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance. Given favorable survival outcomes across strategies, renal preservation is often of paramount concern. To inform clinical decision making, we performed a systematic review and meta-analysis of studies comparing renal functional outcomes for radical nephrectomy, partial nephrectomy, thermal ablation, and active surveillance.

Design, Settings, Participants, & Measurements: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1997 to May 1, 2015 to identify comparative studies reporting renal functional outcomes. Meta-analyses were performed for change in eGFR, incidence of CKD, and AKI.

Results: We found 58 articles reporting on relevant renal functional outcomes. Meta-analyses showed that final eGFR fell 10.5 ml/min per 1.73 m lower for radical nephrectomy compared with partial nephrectomy and indicated higher risk of CKD stage 3 or worse (relative risk, 2.56; 95% confidence interval, 1.97 to 3.32) and ESRD for radical nephrectomy compared with partial nephrectomy. Overall risk of AKI was similar for radical nephrectomy and partial nephrectomy, but studies suggested higher risk for radical nephrectomy among T1a tumors (relative risk, 1.37; 95% confidence interval, 1.13 to 1.66). In general, similar findings of worse renal function for radical nephrectomy compared with thermal ablation and active surveillance were observed. No differences in renal functional outcomes were observed for partial nephrectomy versus thermal ablation. The overall rate of ESRD was low among all management strategies (0.4%-2.8%).

Conclusions: Renal functional implications varied across management strategies for localized renal masses, with worse postoperative renal function for patients undergoing radical nephrectomy compared with other strategies and similar outcomes for partial nephrectomy and thermal ablation. Further attention is needed to quantify the changes in renal function associated with active surveillance and nephron-sparing approaches for patients with preexisting CKD.
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http://dx.doi.org/10.2215/CJN.11941116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498358PMC
July 2017

Evaluation of gender-based disparities in time from initial haematuria presentation to upper tract urothelial carcinoma diagnosis: analysis of a nationwide insurance claims database.

BJU Int 2017 09 17;120(3):377-386. Epub 2017 May 17.

James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To investigate the length of time from initial haematuria presentation to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on this duration.

Patients And Methods: Patients with haematuria claims in the year prior to UTUC diagnosis were identified from the MarketScan database (2010-2014). Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC diagnosis. Multivariable Poisson regression models were used to determine factors associated with delayed UTUC diagnosis.

Results: Among 1 326 patients with UTUC, 469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95% CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists, UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new (RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94, 95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR 1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI 0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR 1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis.

Conclusion: A UTUC diagnosis was made >90 days after haematuria presentation in approximately one-third of patients. Men experienced a longer median interval from haematuria to UTUC diagnosis compared with women, but male gender was not an independent predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation were strongly associated with delayed diagnosis, especially among patients initially seen by non-urologists. Future interventions should focus on development of non-invasive techniques to improve clinical risk stratification of patients presenting with haematuria and to educate practitioners, especially non-urologists, with regard to the importance of a thoughtful haematuria evaluation and the common mimickers of UTUC, to help reduce delays in diagnosis.
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http://dx.doi.org/10.1111/bju.13878DOI Listing
September 2017

Mortality trends and the impact of lymphadenectomy on survival for renal cell carcinoma patients with distant metastasis.

Can Urol Assoc J 2016 Nov-Dec;10(11-12):389-395

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, United States.

Introduction: Current treatment paradigms for metastatic renal cell carcinoma (mRCC) invoke a combination of surgical and systemic therapies. We sought to quantify trends in mortality and performance of lymphadenectomy, as well as impact on survival for patients with mRCC.

Methods: The Surveillance, Epidemiology, and End Results registry (SEER) (1988-2011) identified patients with mRCC. Kaplan-Meier curves and Cox proportional hazards models with competing risks regression were employed to assess survival.

Results: 15 060 patients with mRCC were identified, with 6316 (41.9%) undergoing cytoreductive nephrectomy. Mean number of lymph nodes removed was 6.2, with mean 3.3 positive nodes among 1018 (43.9%) patients with positive nodes. Median overall survival (OS) increased from seven to 11 months (1999-2010), and finding a positive node decreased median cancer survival from 22 to nine months. Cancer-specific survival (CSS) showed significant decreases in mortality after 2005 (hazard ratio [HR] 0.71 [0.60-0.83] comparing 2010 to 1990). Lymphadenectomy was associated with decreased OS (HR 1.10 [1.03-1.16]; p=0.002) due to decreased CSS (HR 1.10 [1.04-1.17]; p<0.001) without increase in other-cause mortality (HR 0.94 [0.79-1.11]; p=0.455). However, more extensive lymphadenectomy ≥3 lymph nodes removed did not significantly impact OS or CSS. Number of positive lymph nodes was associated with decreased CSS.

Conclusions: mRCC continues to carry a poor prognosis, but current treatment paradigms have led to modest improvements in OS and CSS in recent years. Lymphadenectomy was found to play a prognostic rather than therapeutic role in the management of mRCC. The performance of lymphadenectomy should be limited based on clinical judgment and better incorporated into randomized trials of new systemic therapies to identify scenarios where implementation may improve survival.
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http://dx.doi.org/10.5489/cuaj.1999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167593PMC
January 2017

Partial vs Radical Nephrectomy for T1-T2 Renal Masses in the Elderly: Comparison of Complications, Renal Function, and Oncologic Outcomes.

Urology 2017 Feb 23;100:151-157. Epub 2016 Nov 23.

Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, Baltimore, MD.

Objective: To compare outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in patients 65 years and older.

Materials And Methods: Our institutional renal mass registry was queried for patients 65 and older with solitary cT1-T2 renal mass resected by PN or RN. Clinicopathologic features and perioperative outcomes were compared between groups. Renal function outcomes measured by change in estimated glomerular filtration rate (eGFR) and freedom from eGFR< 45 mL/min/1.73 m were analyzed. Multivariate Cox proportional hazard models for overall survival and cancer-specific survival were analyzed.

Results: Overall, 787 patients met inclusion criteria. Of these, 437 (55.5%) underwent PN and 350 (44.5%) underwent RN. Median follow-up was 36 months. Patients in the PN cohort were younger (median age 70.3 years vs 71.9 years, P < .001), had lower American Society of Anesthesiologists scores (2.6 vs 2.8, P = .001), smaller tumors (tumor diameter 2.8 cm vs 5.0 cm, P < .001), and lower proportion of renal cell carcinoma (76.7% vs 87.4%, P < .001). Perioperative outcomes were similar between PN and RN groups as were complications (37.8% vs 38.9%). Estimated change in eGFR was less in PN vs RN (6.4 vs 19.7, P < .001) at last follow-up. Overall survival and cancer-specific survival were equivalent between modalities.

Conclusion: Because the renal functional benefit of PN is realized over many years and the procedure has a higher historical complication rate than RN, some suspected elderly patients might benefit more from RN over PN. However, these data suggest that elderly patients are not harmed and may potentially benefit from PN. Age alone should not be a contraindication to nephron-sparing surgery.
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http://dx.doi.org/10.1016/j.urology.2016.10.047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274548PMC
February 2017

Longer average blood storage duration is associated with increased risk of infection and overall morbidity following radical cystectomy.

Urol Oncol 2017 02 19;35(2):38.e17-38.e24. Epub 2016 Oct 19.

The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Patients with bladder cancer undergoing radical cystectomy (RC) experience high rates of perioperative blood transfusions (PBTs) and morbidity. The aim of this study was to evaluate the effect of blood storage duration on the risk of adverse perioperative outcomes in this high-risk patient population.

Materials And Methods: In a retrospective review of RC patients from 2010 to 2014 who received PBTs, the average storage duration for all units transfused was used to classify patients as receiving older blood using 3 different definitions (≥21 days,≥28 days, and≥35 days). Multivariable Poisson regression models were used to determine the adjusted relative risk of perioperative infections and overall morbidity in those given older blood compared to fresher blood.

Results: Of the 451 patients undergoing RC, 205 (45%) received nonirradiated PBTs. In multivariable modeling, increasing average blood storage duration, as a continuous variable, was associated with an increased risk of infections (risk ratio [RR] = 1.08 per day, 95% CI: 1.01-1.17) and overall morbidity (RR = 1.08 per day, 95% CI: 1.01-1.15). Furthermore, ≥28-day blood storage (vs.<28) was associated with increased infections (RR = 2.69, 95% CI: 1.18-6.14) and morbidity (RR = 2.54, 95% CI: 1.31-4.95), and ≥35-day blood storage (vs.<35) was also associated with increased infections (RR = 2.83, 95% CI: 1.42-5.66) and morbidity (RR = 3.35, 95% CI: 1.95-5.77).

Conclusions: Although blood is stored up to 42 days, storage≥28 days may expose RC patients to increased perioperative infections and overall morbidity compared with storage<28 days. Prospective cohort studies are warranted in cystectomy and other high-risk surgical oncology patients to better determine the effect of blood storage duration.
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http://dx.doi.org/10.1016/j.urolonc.2016.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222715PMC
February 2017