Brady Presentations at the Mid-Atlantic American Urological Association Meeting, 2014

The Mid-Atlantic Section of the American Urological Association has met annually since 1941. This year the meeting is in Baltimore and offers the opportunity for urologists in practice, small and large hospitals to meet, share ideas and build lasting relationships. This year the Brady Urological Institute is well-represented. Some of the highlights include:

Arthur L. Burnett, MD, MBA

• A special topic lecture by Arthur Burnett on the "Efficacy of Early Penile Rehabilitation Following Radical Prostatectomy: Myth or Reality," Thursday, 3pm.
• Point/Counterpoint sessions led by:
  • Stephen Schatz on Endoscopic Management of BPH, Friday, 10:45am
  • Trinity Bivalacqua on BCG Refractory Superficial Bladder Cancer, Friday, 4:00pm
• Video Case Discussion of laparoscopic and robotic complications by Christian Pavlovich and Misop Han

In addition, faculty members, research fellows and residents will be giving over 25 podium and poster presentations over the course of three days. 

A full schedule of the Brady events are listed below.
To see the full listing of presentations and abstracts click here. 

ThurSDAY, September 18

SCIENTIFIC SESSION 1: 2-3pm

6. Percent Lymph Node Involvement Predicts Mortality after Inguinal Lymph Node Dissection for Penile Cancer. Mark W. Ball, Joan Ko, Deborah Kaye, George Netto, Stephania Bezerra, Arthur L Burnett, Trinity Bivalacqua.

MODERATED POSTER SESSION 1: 2-3pm

MP7.     Sickle Cell Disease in Priapism: Disparities in Care? Gregory A. Joice, Max Kates, Nikolai Sopko, Johanna Hannan, Trinity Bivalacqua.
MP9. Quantification of Feulgen Stain (DNA) Nuclear Morphometry Predicts Prostate Cancer Aggressiveness. Aniq ur rehman Gajdhar, Guangjing Zhul, James E. Verdone, Christine Davis, Jonathan I. Epstein, Robert W. Veltri.
MP11.     A Human Prostatic Bacterial Isolate Alters the Prostatic Microenvironment and Accelerates Prostate Cancer Progression. Brian W. Simonsl, Nicholas M. Durham, Tullia Bruno, Joseph Grosso, Anthony Schaeffer, Ashley E. Ross, Paula Hurley, David M. Berman, Charles G. Drakel, Praveen Thumbikaf, Edward M. Schaeffer.

DISPLAY POSTERS: 2P-8P

P5. Rnaseh2a Roles In Regulating Prostate Cancer Cell Cycle And Survival. Zhenhua Huang, Sr., Edward Schaeffer, Sr., Ashley Ross.
P15. Priapism Impact Profile (PIP) Questionnaire: Development and Initial Evaluation. Arthur L Burnett, Uzoma A. Anele, Irene N. Trueheart.
P17. Identification of Men With The Highest Risk of Early Disease Recurrence After Radical Prostatectomy. Debasish Sundi, Vinson Wang, Phillip M. Pierorazio, Misop Han, Alan W. Partin, Phuoc Tran, Ashley E. Ross, Trinity Bivalacqua.
P19. Robotic Retroperitoneal Lymph Node Dissection for Clinical Stage I NSGCT: Initial Study of Feasibility and Comparative Analysis. Mark W. Ball, GautamJayram, MichaelA. Gorin, Phillip M. Pierorazio, Mohamad E. Allaf.
P20. Grade Reclassification on Active Surveillance: Age Matters. Jeffrey Tosoian, Bruce Trock, Max Kates, Patricia Landis,Jonathan I. Epstein, H. Ballentine Carter.
P23. National Resource Utilization In Radical Cystectomy For Bladder Cancer. Jen Jane Liu, Nilay Gandhi, Christian Pavlovich, Trinity Bivalacqua.
P24. Glycolysis Is Necessary For Cell Motility And Cytoskeleton Remodeling In Epithelial To Mesenchymal Transition In Prostate Cancer Cells. Takumi Shiraish P,Jessie Huang, James E. Verdone, James Hernandez', Steven M. Mooney, StevenS. An, Kennth J. Pienta.
P25. Predicting the Risk of Non Organ Confined Prostate Cancer When Perineural Invasion Is Found on Biopsy. Michael A. Gorin, Heather Chalfin, Jonathan I. Epstein, Zhaoyong Feng, Alan W. Partin, Bruce Trock.
P27. Secondary Re Closure in Classic Bladder Exstrophy: The Johns Hopkins Experience. Brian M. Inouye, Heather N. DiCarlo, Ezekiel E. Young, Ali Tourchi,John Gearhart.

SPECIAL TOPIC LECTURE: 3-345p

"Efficacy of Early Penile Rehabilitation Following Radical Prostatectomy: Myth or Reality" -- Presenter: Arthur Burnett, M.D.

SCIENTIFIC SESSION 2: 330-4pm

8. 5-year Analysis of A MultiInstitutional, Prospective Clinical Trial of Delayed Intervention And Surveillance For Small Renal Masses: The Dissrm Registry. Phillip M. Pierorazio, MichaelA. Gorin, Mark W. Ball, Bruce Trock, Mohamad E. Allaf.
14. Do PreBiopsy Rectal Swabs for FluoroquiQolone Resistance Reduce Prostate BiopsyRelated Infections? Jason E. Michaud, Aniq Gajdhar, Lucinda Robinson, Stephen M. Schatz, Pravin K. Rao, E. James Wright, Christian P. Pavlovich.

MODERATED POSTER SESSION 2: 3:45-4-45pm

MP14. Phenotypic Heterogeneity in Small Renal Masses. Mark W. Ball, Stephania Bezerra, Michael A. Gorin, Christian P. Pavlovich, Phillip M. Pierorazio, George]. Netto, Mohamad E. Allaf.
MP16. Risk Factors for IntraProstatic Incision Into Malignant Glands at Radical Prostatectomy Nathaniel Readal, SungWoo Park, Bruce Trock, Elizabeth Humphreys, Jonathan I. Epstein, Alan W. Partin, Misop Han.
MP17. Predict Prostate Cancer Aggression with Multiple Biomarkers Using a Novel Quantitative Tissue Immunoassay. Guangjing Zhul, Zhi Uu, Christhunesa S. Christudass,Jonathan I. Epstein, Hui Zhang, Joon Yong Chung, Stephen M. Hewitt, Robert W. Veltri.
MPI5. Erectile Dysfunction after Recurrent Ischemic Priapism in Patients With and Without Sickle Cell Disease: A Characterization and Comparative Analysis of Risk Factors. Uzoma A. Anele, Irene N. Trueheart, Arthur L Burnett.
MP22. The Financial Impact of Robotic Technology for Partial and Radical Nephrectomy. Max Kates, Mark W. Ball, Hiten D. Patel, Michael A. Gorin, PhillipP. Pierorazio, Mohamad E. Allaf.
MP24. Increased a actin and TGFj31 Levels in Bladder Exstrophy Smooth Muscle Cells. Ezekiel E. Young', Eric Z Massanyi, Heather DiCarlo, Brian Inouye, John P. Gearhart, Larissa A. Shimoda.

FRIDAY, September 19

SCIENTIFIC SESSION 3: 745-9am

21. Long:-term Erectile Function Outcomes of Patients In A Randomized Controlled Trial of Nightly Vs OnDemand Penile Rehabilitation With Sildenafil After Nerve sparing Radical Prostatectomy. Nilay M. Gandhi, Lynda Z. Mettee, Zhaoyong Feng, Bruce Trock, Christian P. Pavlovich.
22. Variability in Medicare Utilization and Payment Among Urologists. Joan S. Ko, Heather Chalfin, Bruce Trock, Zhaoyong Feng, Elizabeth Humphreys, Sung-Woo Park, H. Ballentine Carter, Misop Han.

POINT-COUNTERPOINT: 1045-1130am

Endoscopic Management of Benign Prostatic Hyperplasia (BPH):Greenlight KTP laser vs. Bipolar TURP -- Moderator: Stephen Schatz, MD
Greenlight KTP: Gregg Eure, M.D. Urology of Virginia, Virginia Beach, VA
Bipolar TURP: William Jaffe, M.D. Penn Presbyterian Medical Center, Philadelphia, PA

VIDEO CASE PANEL DISCUSSION: 2-3pm

Management of Intraoperative Laparoscopic and Robotic Complications (or what to do when the sh.. hits the fan)
Moderators: Misop Han, M.D., Johns Hopkins Hospital, Baltimore, MD; Christian Pavlovich, M.D., Johns Hopkins, Baltimore, MD
Panelists:
David Chen, M.D., Fox Chase Cancer Center, Rockledge, PA
Costas Lallas, M.D., Thomas Jefferson University, Philadelphia, PA
Thomas Jarrett, M.D., George Washington University, Washington, DC

SCIENTIFIC SESSION 4: 3-4pm

25. Robotic Simple Prostatectomy for Symptomatic Large-Gland BPH: Safety, Feasibility, and Comparative Analysis. Mark W. Ball, GautamJayram, Christian P. Pavlovich, Misop Han.
28. Neoadjuvant Chemotherapy Prediction of Extravesical Cancer Control Based Off Pathologic Staging. Nilay M. Gandhi, Alex Baras,Jen Jane-Uu, Mark Schoenberg, George Netto, Trinity Bivalacqua.
30. African American Race is Associated with Adverse Oncologic Outcomes Following Prostatectomy: LongrTerm Follow Up. Farzana Faisal, Debasish Sundi, Ashley     Ross, Elizabeth R Humphreys, Alan W. Partin, Misop Han, Edward M. Schaeffer.

POINT-COUNTERPOINT: 4-445pm

BCG Refractory Superficial Bladder Cancer: Early Cystectomy vs.Salvage Intravesical Therapy
Moderators: Matthew Kaag, M.D., Penn State Hershey Medical Center, Hershey, PA
Early Cystectomy: Thomas Guzzo, M.D., University of Pennsylvania, Philadelphia, PA
Salvage Intravesical Therapy: Trinity Bivalacqua, M.D., Ph.D., Johns Hopkins Medical Center, Baltimore, MD

Dogs Detect Prostate Cancer: Give Hope for Better Diagnostic Test

German shepherds, Liu and Zoe, were trained to detect
prostate cancer in urine samples.

The diagnosis of prostate cancer is most often prompted by an elevated PSA (prostate specific antigen) level, or less commonly an abnormal digital rectal examination. An abnormality in PSA or digital rectal examination often prompts a prostate biopsy – almost X performed per year in the United States. However, PSA testing and digital rectal examination are far from perfect (See our prior blog on PSA Screening Controversies). Part of this stems from the fact that both normal and cancerous prostate cells make PSA. Distinguishing a normal PSA from a "cancerous" PSA can be very difficult. Therefore, the accuracy of detecting prostate cancer following an abnormal PSA test is only 30% - with a lot of room for improvement!!

An average dog nose has 200 million olfactory or smell-
sensing cells!  The average human has 5 million.

PSA is not the only molecule that prostate and prostate cancer cells release. For many years, researchers have been looking at the urine of men with and without prostate cancer in search of a better diagnostic test. Recently, researchers in Italy used two highly trained German shepherds to evaluate urine samples of men with and without prostate cancer – and the dogs were correct 98% of the time. Dogs have a dramatically stronger sense of smell than humans. The average human nose has approximately 5 million olfactory cells that detect volatile (airborne) compounds (our sense of smell) – dogs have 200 million. We have known this for years, making use of our canine friends in law enforcement, to detect drugs and bombs; and in medicine. In several studies, dogs have been able to detect the onset of epileptic seizures and to aid in the diagnosis of breast, lung and bladder cancers.

This study was completed in Italy with two German shepherds, a team of urologists, veterinarians, dog handlers, and over 900 urine samples from patients with and without prostate cancer. Three-hundred and sixty two men had prostate cancer in various stages, from very early, low-risk cancer to metastatic disease; the 540 men in the control group had neither benign prostatic hyperplasia nor prostate cancer. The dogs were exposed to half a dozen specimens at a time and were trained to sit down when they detected a cancer. The dogs were accurate in detecting either cancer or no cancer in 98% of cases. In fact, the sensitivity (or ability of the dogs to rule out cancer) was >99%; and if they identified cancer, they were right 97% of the time (specificity).

One of the biggest problems in using dogs in "sniffing" tests is that they can pick up on queues from their trainers. In this experiment, the trainers were completely blinded to the samples and the dogs were left to determine the status of the urine on their own. To ensure well-trained dogs, the process of teaching the dogs to smell cancer took over six months.

One of the biggest questions that remains is what were the dogs actually smelling? The dogs could be smelling a single molecule present in the cancer or a combination of chemicals produced by the cancer cells. In fact, it may not even be a cancer molecule, but a product of the microenvironment of that man's prostate that allowed the cancer to grow in the first place. Additional laboratory studies using complex gas chromatographers or "electronic noses" are needed to determine the exact molecule or chemicals present in the urine of men with prostate cancer. Whether dogs are in the future of prostate cancer detection remains to be seen, but this study proves that there is something detectable in the urine of men with prostate cancer that can be detected with incredible precision!

This study was presented by Dr. Gian Luigi Taverna, MD, at the American Urological Association (AUA) Annual Meeting in Orlando, Florida in May.  Read the abstract below:

PD19-01: Prostate Cancer Urine Detection Through Highly-Trained Dogs’ Olfactory System: A Real Clinical Opportunity 
Gianluigi Taverna*, Milan, Italy, Lorenzo Tidu, Grosseto, Italy, Fabio Grizzi, Guido Giusti, Mauro Seveso, Alessio Benetti, Rodolfo Hurle, Silvia Zandegiacomo, Luisa Pasini, Alberto Mandressi, Pierpaolo Graziotti, Milan, Italy
Abstract: PD19-01 
Introduction and Objectives: The analysis of volatile organic compounds (VOCs) in urines is a promising approach to cancer detection. Here, we establish the level of accuracy at which a rigorously trained canine olfactory system can recognize specific prostate cancer-VOCs in urine samples, thus reducing unnecessary prostate biopsies, and pinpointing patients at high-risk for prostate cancer. 
Methods: A total of 677 subjects were investigated. All the subjects included in the study were placed in one of two main Groups: Prostate Cancer Group (n = 320) and Control Group (n = 357). Prostate Cancer Group includes patients with PC ranging from those at very-low risk to metastatic PC. Control Group includes a large and heterogeneous cohort of healthy subjects or patients affected by non-neoplastic diseases or non-prostatic tumors. Each patient's clinical status and therapeutic regiment was known. We took into consideration all predictive values currently used in the clinical practice for prostate cancer management. Two dogs and a full-time, highly specialized, multidisciplinary team was dedicated. We have standardized a “work training” procedure and eliminated any possible olfactory interference. Each test was carried out blindfold. 
Results: The dogs achieved the following performances: Dog 1: sensitivity 100%, specificity 97.8%, accuracy 98.9%. Dog 2: sensitivity 98.6%, specificity 95.9%; accuracy 97.3%. When considered together, Dogs 1 + 2, we found an accuracy of 98.1% with a sensitivity of 99.2% and a specificity of 97.1%. Whether excluded the female control sub-groups we found that Dog 1 achieved a sensitivity of 100% and a specificity of 97.9%, while Dog 2 a sensitivity of 98.6% and a specificity of 94.5%. When evaluating the wrongly detected cases no differences were found between epidemiological, clinical or histopathological characteristics. 
Conclusions: The present study first demonstrates that a trained canine olfactory system detects specific PC-VOCs in urine samples from a large number of patients with PC at different stages and risks versus a heterogeneous control group, which is unthinkable in current clinical urological practice. Thanks to the early intuition, we have definitely turned what used to seem a myth into a real clinical opportunity.

New AUA Guidelines for Kidney Stones

Brian Matlaga, MD

The American Urological Association (AUA) recently released GUIDELINES FOR THE MEDICAL MANAGEMENT OF KIDNEY STONES.  Kidney stones are a common problem in the United States and are a disease with a high-rate of recurrence.  There are well-proven, effective treatments for the prevention of kidney stones.  However there is evidence that these treatment regimens are underutilized.  Brian Matlaga, MD, Associate Professor of Urology and Director of Stone Disease at the Brady Urological Institute was a member of the guideline committee tasked with standardizing the treatment of kidney stones.  Here he reviews some of the important features of the new Guideline.  Salient point are broken down into Evaluation, Dietary Therapies, Pharmacologic Therapies and Follow-Up.  Important studies are referenced.

EVALUATION

All patients with a newly diagnosed stone should undergo a screening evaluation.
This should include a dietary and medical history, serum chemistry evaluation, urinalysis and urine culture, and a stone analysis.

Important aspects of the medical history include signs, symptoms and comorbidities associated with stone disease (renal tubular acidosis, primary hyperparathyroidism, diabetes, gout, obesity); a dietary history (fluid, calcium, protein and fruit/vegetable intake); and pertinent medications (topiramate, zonisamide, acetazolamide, triamterene, probenecid, protease inhibitors, vitamin C).

When examining a serum chemistry:

• high calcium and low phosphate can indicate primary hyperparathyroidism
• a serum parathyroid hormone level should be checked only if primary parathyroidism is suspected
• low bicarbonate, low potassium and increased chloride may indicate distal renal tubular acidosis
• increased uric acid can indicate low pH or hyperuricosuria

A stone analysis should be obtained at least once for a patient with stones:

• cystine stones indicate cystinuria
• uric acid stones identify low urinary pH as a target for treatment
• struvite stones may coincide with recurrent urinary tract infections

24-hour metabolic testing should be completed in high-risk patients, interested first-time stone formers and recurrent stone formers.  This is based on data that supersaturation levels in 24-hour urinalyses consistently reflect stone composition and preventive treatments can result in reduction of supersaturation levels in most patients.[1]  

"High-risk" stone formers include those with:

• Family history 
• GI disease/bowel resection
• Gout
• Type II diabetes mellitus
• Obesity
• Distal renal tubular acidosis
• Primary hyperparathyroidism
• Nephrocalcinosis
• Recurrent urinary tract infections
• Children or adolescents
• Solitary kidney

DIET THERAPIES

Clinicians should recommend that all stone formers:

• increase fluid intake to achieve a urine volume of 2.5L each day.  
• limit sodium intake
• consume 1000-1200 mg/day of dietary calcium [2,3]  

Patients with uric acid stones, or calcium stones with high urinary uric acid, should limit intake of animal protein.

PHARMACOLOGIC THERAPIES

Thiazide diuretics should be offered to patients with high or relatively high urinary calcium and recurrent calcium stones.[4]
Potassium citrate should be offered to all patients with recurrent calcium stones and low urinary citrate.[5]
Thiazide diuretics and/or potassium citrate should be offered to patients with recurrent calcium stones and no other identifiable metabolic abnormalities.[6]

Allopurinol should be offered to patients with recurrent calcium oxalate stones, hyperuricosuria and normal urinary calcium.  Allopurinol should not be offered as first-line therapy to patients with uric acid stones, rather treatments to alter urinary pH should be considered.

FOLLOW-UP

Urinary parameters are believed to precede stone recurrence, therefore serial urine collections should be obtained to assess changes in stone risk factors.  Success of any treatment should therefore be gauged by improvement in urinary risk factors and ultimately into reduction in stone events.

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This blog entry was extracted from a recent presentation by Brian Matlaga, MD, the AUA GUIDELINES FOR THE MEDICAL MANAGEMENT OF KIDNEY STONES.  The Guideline Committee was led by Margaret S. Pearle, MD, PhD, Chair, and David S. Goldfarb, MD, Vice-chair.  To read the entire Guideline Document click on the link above or here.

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[1] Parks et al, KI 51: 894, 1997

[2] Borghi et al, J Urol 155: 839, 1996

[3] Borghi et al, NEJM 346:77, 2002

[4] Pearle, Roehrborn et al, J Endourol 13, 1999

[5] Barcelo et al, J Urol 150: 1761, 1993

[6] Ettinger et al, J Urol 158: 2069, 1997

AUA Highlights: Kidney Cancer, by Dr. Pierorazio

Kidney cancer is one of the major diseases treated by urologists and urologic oncologists.  Kidney cancer was well represented at this year's 2014 American Urological Association (AUA) Annual Meeting in Orlando, Florida.  Kidney cancer had a major seat in the AUA plenary sessions and the Society of Urologic Oncology (SUO) Meeting.  In addition, the scientific sessions were well attended and lively discussion often ensued.  Here are some of the highlights and commentary from the meeting, click on the links below to see webcasts or read the abstracts:

During the AUA Plenary: CROSSFIRE - CONTROVERSIES IN UROLOGY, kidney cancer thought-leaders Michael Jewett, Inderbir S. Gill, MD, MCh, Robert G. Uzzo, MD, Michael Blute, MD and John Libertino, MD debated "Minimally Invasive Partial Nephrectomy is the New Gold Standard for Renal Cancer."  (Follow the link above or click here to see the debate)  In general, the debate lacked strong evidence and was an endorsement of expert opinions.  However, Dr. Uzzo did an excellent job and laid out the argument, showing that while no Level 1 Evidence exists comparing minimally-invasive and open Partial Nephrectomy (PN), population-based data demonstrates an ever-increasing use of minimally-invasive surgery (MIS) and improved perioperative outcomes (length of stay, decreased blood loss and lower complications) for MIS.  However, oncologic outcomes (most importantly margin rates and cancer-specific survival) are equivalent between the two approaches.  Drs. Blute and Libertino argued for the continued use of open PN, citing the equivalent oncologic outcomes.  My take home was: there is a role for both minimally-invasive and open partial nephrectomy.  Outcomes are similar and the surgeon should perform the best operation for that given patient and tumor.

In the SUO Meeting, topics ranged from clinically localized to metastatic kidney cancer.  A major topic of focus at this meeting and throughout the week was clinical heterogeneity in kidney cancer. James Hsieh, MD, PhD, laid out an elegant argument for a "River Model" instead of "Branched Evolution" (akin to a tree) for the genetic evolution of kidney tumors.  He argued that as kidney tumors grow and progress, the genetics diverge and converge along several pathways, instead of following a number of linear progressions.  Other topics of interest including percutaneous renal mass biopsy and the treatment of metastatic disease.  Dr. Jewett discussed biopsy for all patients demonstrating a 94% concordance rate of low-grade renal cell carcinoma (RCC) in their Canadian series.  While these concordance rates are promising, they should be taken with consideration that most patients with small renal masses have low-grade tumors and therefore these numbers are skewed to predict insignificant disease.  In contrast, Dr. Uzzo argued for a more thoughtful approach and biopsy in only those patients in whom it would change mangement.  With regard to metastatic cancer, Dr. Figlin laid out a thoughtful paradigm for the treatment of advanced cancers based on objective response to systemic therapy, rather than picking from the list of options currently advocated by groups like the National Comprehensive Cancer Network (NCCN).

KIDNEY CANCER PSEUODOCAPSULE & ENUCLEATION

A number of posters and podiums focused on the biologic boundaries of renal cell carcinoma and its implications for positive surgical margins, enucleation and cancer control.  Alessandro Volpe and colleagues from Milan, Italy demonstrated that 40-50% of RCC invade the pseudocapsule and those tumors had a worse prognosis.  A group from Germany found that patients with a margin of 1mm or less had a higher rate of disease recurrence and kidney cancer death.  Finally, Dr. Ronald Boris and colleagues from Indiana looked at patients with clear-cell RCC and the complete tumor capsule and surrounding inflammation around the tumor.  They found that RCC rarely demonstrated capsular invasion, however found "gaps" in the tumor capsule gaps more often in late stages indicating there may be a loss of immune “control” over capsular penetration when elucidating the aggressive behavior of advanced ccRCC.

PD10-06: Classification of pseudocapsular invasion in organ-confined renal cell carcinoma: correlation with histological variables and prognostic impact.  Alessandro Volpe*, Antonia Di Domenico, Novara, Italy, Enrico Bollito, Turin, Italy, Cristina Bozzola, Novara, Italy, Riccardo Bertolo, Turin, Italy, Luisa Zegna, Paolo De Angelis, Novara, Italy, Daniele Amparore, Francesco Porpiglia, Turin, Italy, Carlo Terrone, Novara, Italy
PD10-08: Prognostic impact of tumor surrounding renal parenchyma in nephron sparing surgery – Is simple enucleation really enough? Stefan Aufderklamm*, Jörg Hennenlotter, Tilman Todenhöfer, Nicolas Senghaas, Georgios Gakis, Marcus Scharpf, Arnulf Stenzl, Christian Schwentner, Tuebingen, Germany
MP30-21: Pathologic variances in tumor capsule properties of clear cell renal cell carcinoma across various clinical stages Joseph M. Jacob*, Dibson D. Gondim, Jose A. Pedrosa, Muhammad T. Idrees, Ronald S. Boris, Indianapolis, IN

ACTIVE SURVEILLANCE FOR KIDNEY CANCER

Active surveillance (AS) was a hot topic given the recent questions of overtreatment in other diseases like prostate cancer.  The Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry is a multi-institutional study led by Johns Hopkins, that has followed nearly 200 patients over the past 5 years.  Six abstracts demonstrated results from DISSRM:

• PD10-09: DISSRM Score is an objective scoring system composed of age, ECOG performance status, tumor size, tumor complexity (RENAL Nephrometry) and Cardiovascular Index that identifies patients most suitable for AS.
• MP54-03: The 1st surveillance image for patients on AS can lead to highly variable growth rates.  Over the course of a year or more, most patients demonstrate a slow growth rate (approximately 1mm/year), however this can be grossly overestimated by the high-variability of GR in the first image within a few months of starting surveillance.  Hear the webcast at UroToday.
• MP54-04: Patients on AS have a decreasing GFR equivalent to patients undergoing PN, while both were superior to Radical Nephrectomy (RN).  It appeared that renal function was unaffected by tumor size or GR, however should be considered when choosing a management strategy.
• MP54-05: Quality-of-life was not adversely affected for patients on AS; in fact they had worse perception of physical health (reflecting their increased comorbidities and advanced age), but no change in mental health over time.
• MP64-09: In this analysis, tumors close to the renal hilum and collecting system had higher growth rates that other tumors, perhaps indicating more aggressive tumors, but at a minimum providing expectations for patients undergoing AS.
• PD17-06: With a median follow-up of 2 years, but a maximum of 5 years, the overall survival was equivalent among patients undergoing immediate treatment of AS. No patients undergoing AS died of kidney cancer.

Other groups also looked at AS cohorts: 

• PD17-04, PD17-05: Dr. Mehrazin and colleagues from Fox Chase looked at their AS experience and found that complex tumors were more likely to grow rapidly and examined outcomes for their patients with larger, cT1b renal tumors.  They found similar growth kinetics for larger and smaller tumors.  They found 34% of patients underwent surgery, but no patients died of kidney cancer.
• MP59-20: Dr. Dorin and colleageus looked at a conglomerate of small renal and complex cystic masses and found low growth rates and progression.  They found that GR decreased with increasing mass size and a 35% rate of intervention at 10-years.

PD10-09: The DISSRM Score: Objective Scoring System Identifies Patients with Small Renal Masses Most Suitable for Active Surveillance.  Phillip Pierorazio, Deborah Kaye*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD

MP54-03: First Surveillance Image for Patients with a Small Renal Mass Should Not Determine Outcome: Results from the DISSRM Registry.  Phillip Pierorazio, Nathaniel Readal*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD

MP54-04: Partial Nephrectomy is Equivalent to Active Surveillance in Preserving Renal Function for Patients with Small Renal Masses.  Matthew Danzig*, Rashed Ghandour, Srinath Kotamarti, Tina Schubert, Arindam RoyChoudhury, New York, NY, Phillip Pierorazio, Baltimore, MD, Ketan Badani, New York, NY, Mohamad Allaf, Baltimore, MD, James McKiernan, New York, NY

MP54-05: Mental Health Not Affected by Active Surveillance for Patients with Small Renal Masses: Quality of Life Results from the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry.  Phillip Pierorazio, Michael Gorin*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD

MP64-09: Prospective Analysis of Tumor Growth Rates Based on Patient Comorbidities and Imaging Characteristics from the DISSRM Registry: Implications for Future Nephron-Sparing Surgery.  Phillip Pierorazio, Mark Ball*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD

PD17-06: Active surveillance for small renal masses non-inferior to primary intervention: 5-year analysis of the multi-institutional, prospective DISSRM (delayed intervention and surveillance for small renal masses) Registry.  Phillip Pierorazio, Mark Ball*, Baltimore, MD, Matthew Danzig, Rashed Ghandour, New York, NY, Peter Chang, Robert Hartman, Andrew Wagner, Boston, MA, James McKiernan, New York, NY, Mohamad Allaf, Baltimore, MD

PD17-04: EXPERIENCE WITH ACTIVE SURVEILLANCE (AS) IN PATIENTS WITH RENAL MASS >4cm: ASSESSMENT OF GROWTH KINETICS AND OUTCOMES.  Reza Mehrazin*, Marc C. Smaldone, Alexander Kutikov, Jeffrey J. Tomaszewski, Tianyu Li, Timothy Ito, Philip Abbosh, Rosalia Viterbo, Richard E. Greenberg, David Y.T. Chen, Robert G. Uzzo, Philadelphia, PA

PD17-05: Tumor Anatomic Complexity Predicts Growth Kinetics of Renal Masses Under Active Surveillance.  Reza Mehrazin*, Marc C. Smaldone, Brian Egleston, Charlie Concodora, Jeffrey J. Tomaszewski, Philip Abbosh, Timothy Ito, Jason Lomboy, Alexander Chow, Rosalia Viterbo, Richard E. Greenberg, David Y.T. Chen, Alexander Kutikov, Robert G. Uzzo, Philadelphia, PA

MP59-20: Active Surveillance of Renal Masses: An Analysis of Growth Kinetics and Clinical Outcomes Stratified by Radiological Characteristics at Diagnosis.  Ryan Dorin, Antonio Cusano*, Max Jackson, Stuart Kesler, Anoop Meraney, Steven Shichman, Hartford, CT

IMPROVING THE DIAGNOSIS OF KIDNEY CANCER

A number of presentations demonstrated improved diagnostic techniques. Differentiating RCC and oncocytoma can be difficult based on enhanced axial imaging.  Simply looking at the presence of hematuria improved the ability to discriminate between the two entities (MP36-14).  In addition, using clinical parameters including tumor size, sex and RENAL nephrometry score could improve the ability to determine benign histology, malignant histology and potentially aggresive tumors (MP40-09).  For instance, women with <3cm tumors and low-complexity tumors had only a 64% chance of malignancy and on 9% had high-grade tumors; while 90% of men with >3cm tumors and nephrometry scores >8 had RCC and 35% had high-grade cancers.  Hear the webcast of this study at UroToday.

MP36-14: Can Hematuria be Used to Predict RCC vs. Oncocytoma Histology? Michael Hanzly*, Terry Creighton, Christine Murekeyisoni,, Elizabeth Devine, Shervin Badkhshan, Michael Mungillo, Thomas Schwaab, Eric Kauffman, Buffalo, NY

MP40-09: Preoperative predictors of malignancy and unfavorable pathology for clinical T1a renal tumors treated with partial nephrectomy.  Mark Ball*, Michael Gorin, Baltimore, MD, Sam Bhayani, St. Louis, MO, Craig Rogers, Detroit, MI, Michael Stifelman, New York, NY, Jihad Kaouk, Homayoun Zargar, Cleveland, OH, Susasn Marshall, New York, NY, Jeffrey Larson, St. Louis, MO, Phillip Pierorazio, Mohamad Allaf, Baltimore, MD

IMPROVING RENAL FUNCTIONAL OUTCOMES AFTER SURGERY

In an impressive, "out-of-the-box" presentation in a basic science section, Drs. Alexander and Dorai from New York Medical College used 5'AMP to induce a gobal hypometabolic state similar to to hibernation and were able to attenuate the effects of renal ischemia in an animal model (MP29-09).  A number of studies looked at surgically-induced chronic kidney disease (CKD-S).  Researchers found that patients who developed CKD-S had worse overall and cancer-specific survival (PD16-02).  The group from Columbia University found that there were no differences in renal functional outcomes or overall survival for patients undergoing PN or RN if they had no CKD or Stage 3 CKD and the only benefits with respect to nephron-sparing surgery was found in patients with intermediate levels of CKD (PD17-10).  Another study found that the benefits of PN were not observed in patients >65 years of age (MP54-20).  The benefits of nephron-sparing surgery with respect to renal function are well understood, however the patients who most benefit from nephron-sparing surgery is still to be defined.  

A number of other studies examined ischemia time and parenchyma saved during PN to predict renal functional outcomes.  Important observations from presentations included: there was no difference between zero ischemia and warm ischemia <30 minutes (MP54-13) and that quantity, not quality of parenchyma saved predicted renal functional outcome (PD17-03).  Finally, an important study using SEER, showed that patients with low-grade or any T1 clear-cell RCC with end-stage renal disease should proceed directly to transplant without a waiting time as there risk of recurrence was negligible and not increased due to immunosuppression (MP59-10).

MP29-09: INDUCTION OF HYPOMETABOLISM AS A NOVEL STRATEGY TO EXTEND WARM ISCHEMIA TIME IN PARTIAL NEPHRECTOMIES.  Bobby Alexander*, Meris James, Andrew Fishman, Michael Grasso, Thambi Dorai, Valhalla, NY
PD16-02: IMPACT OF RENAL SURGERY ON OVERALL, ONCOLOGIC, AND CARDIAC MORTALITY IN PATIENTS WITH STAGE I RENAL CELL CARCINOMA AND WITHOUT PREOPERATIVE RENAL INSUFFICIENCY.  Jason Woo*, Michael Liss, Nishant Patel, San Diego, CA, Reza Mehrazin, Memphis, TN, Hak Lee, San Diego, CA, Anthony Patterson, Jim Wan, Memphis, TN, Ithaar Derweesh, San Diego, CA
PD17-10: Renal Failure Following Partial vs Radical Stratified by Preoperative CKD Stage.  Solomon Woldu*, Matthew Danzig, Rashed Ghandour, Aaron Weinberg, Natasha Leigh, Ruslan Korets, Ketan Badani, James McKiernan, Guarionex Joel DeCastro, New York, NY
MP54-20: Overall survival and renal function of partial and radical nephrectomy among older patients with localized renal cell carcinoma: multicenter study.  Jae Seung Chung*, Busan, Korea, Republic of, Seok Soo Byun, Sang Eun Lee, Sung Kyu Hong, Sang Chul Lee, Seongnam, Korea, Republic of, Chang Wook Jeong, Hyeon Hoe Kim, Cheol Kwak, Ja Hyeon Ku, Seoul, Korea, Republic of, Yong June Kim, Cheongju, Korea, Republic of, Seok Ho Kang, Sung Hoo Hong, Won Suk Choi, Seoul, Korea, Republic of
MP54-13: The effects of prolonged warm ischemia on late renal function after robotic partial nephrectomy.  Oktay Akca*, Homayoun S. Zargar, Luis Felipe Brandao, Humberto Laydner, Riccardo Autorino, Jayram Krishnan, Dinesh Samarasekera, George P. Haber, Robert J. Stein, Jihad H. Kaouk, Cleveland, OH
MP59-10: Immunosuppression does not worsen disease-specific survival among patients with renal carcinoma who have undergone renal transplantation.  Bhalaajee Meenaski-Sundaram*, Oklahoma City, OK, Oluwakayode Adejoro, Sean Elliot, Minneapolis, MN, Puneet Sindhwani, Joel Slaton, Oklahoma City, OK
PD17-03: POORLY FUNCTIONING KIDNEYS RECOVER FROM ISCHEMIA DURING PARTIAL NEPHRECTOMY AS WELL AS STRONGLY FUNCTIONING KIDNEYS.  Maria Carmen Mir*, Toshio Takagi, Rebecca Campbell, Nidhi Sharma, Erick Remer, Jianbo Li, Sevag Demirjian, Jihad Kaouk, Steve C Campbell, Cleveland, OH

KIDNEY CANCER SURVIVAL & TREATMENT OF ADVANCED DISEASE

Finally, in the area of advanced disease, the group from MD Anderson demonstrated that lymph node dissection was protective in patients with T4 and metastatic disease (MP36-20).  For patients with renal vein thrombus, BMI<20, preoperative anemia, renal fat invasion, non-clear cell histology and grade 4 disease predicted survival (PD16-04).  Another presentation demonstrated that blood transfusion, in a dose-dependent fashion, was associated with worse survival for patients undergoing surgery for RCC (PD16-03).  Patients with >1cm and multiple lung nodules were more likely to have metastatic RCC (PD17-07).  When considering patients at highest risk for recurrence, those who recurred within 1 year of initial surgery had the highest mortality from RCC with rates of cancer-specific mortality decreasing with later follow-up (MP40-14).

MP36-20: Survival and Prognostic Variables Predicting Survival in T4 Renal Cell Carcinoma.  Dae Y. Kim*, Christopher G. Wood, Angie Busch, Wei Qiao, Pheroze Tamboli, Eric Jonasch, Nizar M. Tannir, Surena F. Matin, Jose A. Karam, Houston, TX
PD16-04: CURATIVE SURGERY IN RCC WITH THROMBUS; A COMPREHENSIVE RISK MODEL FROM A MODERN MULTICENTER ANALYSIS.  Tyler M. Bauman*, Madison, WI, Vitaly Margulis, Dallas, TX, Christopher G. Wood, Houston, TX, William P. Christensen, Madison, WI, Vishnukamal Golla, Houston, TX, Ramy F. Youssef, Laura-Maria Krabbe, Dallas, TX, David F. Jarrard, Tracy M. Downs, E. Jason Abel, Madison, WIPD16-03: The Impact of Perioperative Blood Transfusion on Survival Following Nephrectomy for Non Metastatic Renal Cell Carcinoma.  Brian Linder*, R. Houston Thompson, Bradley Leibovich, John Cheville, Christine Lohse, Dennis Gastineau, Stephen Boorjian, Rochester, MN
PD17-07: The Clinical Significance of Indeterminate Pulmonary Nodules in Renal Cell Carcinoma.  Roy Mano*, Emily Vertosick, Alexander Sankin, Michael Chevinsky, Yaniv Larish, Christopher Jakubowski, Andreas Hoetker, A Ari Hakimi, Daniel Sjoberg, Oguz Akin, Paul Russo, New York, NY
MP40-14: Predictors of cancer-specific survival after disease recurrence in patients with renal cell carcinoma: The effect of time to recurrence.  Malte Rieken*, Luis Kluth, Evanguelos Xylinas, New York, NY, Umberto Capitanio, Alberto Briganti, Milan, Italy, Laura-Maria Krabbe, Vitaly Margulis, Dallas, TX, Jay Raman, Mikhail Regelman, Hershey, PA, Tobias Klatte, Vienna, Austria, Matthew Kent, Daniel Sjoberg, New York, NY, Alexander Bachmann, Basel, Switzerland, Shahrokh Shariat, Vienna, Austria

To read the entire abstract follow the links below:
For podium presentations (PD5-), click here.
For poster presentations (MP10-), click here.

Phillip M. Pierorazio, MD is an Assistant Professor of Urology & Oncology, Director of the DISSRM Registry and Director of the Division of Testicular Cancer at the Brady Urological Institute at Johns Hopkins.  

AUA Best Abstracts from the Residents

The American Urological Assocation (AUA) Annual Meeting is a wonderful opportunity for urology residents, trainees and medical students to showcase the hard-work and research they have performed, as well as to meet other urologists, learn about the field and see cutting edge data.  Each of the residents below attended this year's AUA Meeting in Orlando, Florida to present individual research.  In addition to presenting their own work, they attended scientific sessions and interacted with other researchers.  Each resident has selected their own "Highlights" from the meeting and discuss them below.

To read the entire abstract follow the links below:
For podium presentations (PD5-), click here.
For poster presentations (MP10-), click here.

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Nilay Gandhi, MD; Senior Assistant (U3) Resident

**MP34-07: Differential Gene Expression In Responsive Versus Recurrent Non-muscle Invasive High-grade Urothelial Carcinomas After Induction BCG. Philip Ho*, Daniel Willis, Houston, TX, Saad Aldousari, Kuwait, Kuwait, Charles Guo, Colin Dinney, Xifeng Wu, Ashish Kamat, Houston, TX

Interesting research assessing mRNA differential expression identifying significant increase in the expression of genes involved with cell cycle progression, cell death/necrosis/apoptosis, and migration of antigen presenting cells. Extremely important to identify predictors of BCG response given likelihood of patient side effects and up to 40% failure rate after induction BCG.
**Also selected by Max Kates (below)


MP55-13: INTRAOPERATIVE BLOOD TRANSFUSION DURING RADICAL CYSTECTOMY INCREASES THE RISK OF DEATH FROM BLADDER CANCER COMPARED TO POSTOPERATIVE TRANSFUSION.  E. Jason Abel*, Madison, WI, Brian J. Linder, Rochester, MN, Tracy M. Downs, Tyler M. Bauman, Madison, WI, R. Houston Thompson, Prabin Thapa, Rochester, MN, Octavia N. Devon, Madison, WI, Robert F. Tarrell, Igor Frank, Matthew K. Tollefson, Rochester, MN, David F. Jarrard, Madison, WI, Stephen A. Boorjian, Rochester, MN

Assessment of 360 patients identifying 30% increased risk of death from bladder cancer in patients receiving intraoperative transfusion compared to those postoperatively. Also noted within older patients with more advanced stage disease. Critiques include likely multifactorial, requires stage for stage assessment to identify true clinical impact, no neoadjuvant chemo pts included.

Debasish Sundi, MD; Senior Assistant (U3) Resident

MP61-19: A novel role of the transcription factor TCF21 as a suppressor of bladder cancer metastasis.  Sima Porten*, Beat Roth, Jonathan Melquist, Woonyoung Choi, Shanna Pretzsch, Jolanta Bondaruk, Charles Guo, Bogdan Czerniak, David McConkey, Colin Dinney, Houston, TX

The transcription factor TCF21 may serve as a mediator of the transition from local to metastatic urothelial cancer.  A number of studies focused at this year's AUA looked at gene expression in the transition from local, to invasive, to metastatic urothelial cancer.  I am intrigued by this transition, and a better understanding of these gene transcripts, like the transciption factor in this presentation, may improve our understanding (and therefore treatment) of urothelial cancer metastases.


**PD34-08: Disparities in survival for California men with prosate cancer are more associated with socioeconomics than either race or insurance status. Thenappan Chandrasekar*, Kari Fish, Christopher Evans, Ralph DeVere White, Marc Dall'Era, Sacramento, CA

The podium is one of the three reports of Black race as an independent risk factor for adverse oncologic outcomes after radical prostatectomy after controlling for SES.  The other two include a 15 year-old study of SEER from our colleagues at UCSF and work done at Johns Hopkins by Farzana Faisal (below).
**Also selected by Farzana Faisal (below).

Mark W. Ball, MD; Lab Resident

MP59-18 Chronic Kidney Disease Due to Surgery (CKD-S): Relative Rates of Progression and Survival. Sevag Demirjian*, Cleveland, OH, Brian Lane, Grand Rapids, MI, Ithaar Derweesh, La Jolla, CA, Toshio Takagi, Amr Fergany, Steven Campbell, Cleveland, OH

This study evaluated progression of renal failure in a cohort of patients with GFR < 60 after surgery by classifying as  surgical chronic kidney diseaes (CKD) (normal  GFR before surgery) and medical CKD (low GFR before surgery) and a medical CKD only cohort. Overall patients with surgical CKD has less progression and increased overall survival compared to patients in either medical CKD cohort. This work bolsters previous work from the authors that shows a clear distinction between medical and surgical CKD.

MP54-20: Overall survival and renal function of partial and radical nephrectomy among older patients with localized renal cell carcinoma: multicenter study.  Jae Seung Chung*, Busan, Korea, Republic of, Seok Soo Byun, Sang Eun Lee, Sung Kyu Hong, Sang Chul Lee, Seongnam, Korea, Republic of, Chang Wook Jeong, Hyeon Hoe Kim, Cheol Kwak, Ja Hyeon Ku, Seoul, Korea, Republic of, Yong June Kim, Cheongju, Korea, Republic of, Seok Ho Kang, Sung Hoo Hong, Won Suk Choi, Seoul, Korea, Republic of

This multi-institutional study from Korea evaluated renal functional outcomes in patients >65 after radical and partial nephrecotmy. The authors found an increased incidence of new onset CKD in the RN cohort compared to partial nephrectomy (66.7 vs 26.3) but no difference in overall survival. Although not a perfect study and far from the whole story, this study addds another piece of evidence that may help define the ideal candidates for nephron-sparing surgery.

Jeffrey Tosoian, MD; Junior (U1) Resident

MP55-06: Prostate sparing cystectomy: 20 years single center experience.

Laura Mertens*, Richard Meijer, Remco de Vries, Jakko Nieuwenhuijzen, Henk van der Poel, Axel Bex, Bas van Rhijn, Wim Meinhardt, Simon Horenblas. Amsterdam, Netherlands.

These authors reported their experience over 20 years with performing prostate-sparing cystectomy (PSC) for muscle-invasive bladder cancer (MIBC) or refractory high risk non-MIBC, as opposed to the conventional radical cystoprostatectomy (RC), which is the generally accepted standard of care. They describe excellent disease-specific survival of 76.2% and 66.5% at 2 and 5 years, respectively. Functional outcomes were similarly impressive, with daytime continence, nighttime continence, and erectile function maintained in 96.2%, 81.9%, and 89.7%, respectively. 

As a junior resident who continues to learn about both standard and non-standard therapies, this abstract caught my attention because it diverged from my expectations. I am eager to compare these findings with the more conventional cystoprostatectomy. The authors note one local recurrence in the remnant prostatic epithelium, and I would be interested to learn more about this patient’s subsequent course. If this recurrence could presumably have been avoided by performing conventional RC, that raises an important question: as both patients and urologic oncologists, are we willing to risk one unnecessary recurrence for the possibility of improved functionality? I suspect the answer may vary significantly based on who you ask.

MP27-13: The impact on the type of ureteral stent to patient symptoms using USSQ : A prospective randomized controlled study.  Hyoungkeun Park*, Sangrak Bae, Sunghyun Paick, Hyunwoo Kim, Jutae Seo, Joonchul Kim, Wonhee Park, Yongsoo Lho, Hyeonggon Kim. Seoul, Korea.

These authors performed a randomized controlled trial comparing stent-related symptoms in patients treated with a conventional double-j ureteral stent versus a newly emerging stent which contains a softer distal end.  While the softer distal tip stents were designed with hopes of improving stent-related symptoms, hey ultimately found no significant differences between the two stent groups in reported urinary symptoms or pain as reported by the visual analogue pain scale.

This abstract stood out to me because it investigates what any urologic resident will tell you is a very common problem. In addition to being prevalent, stent pain is rather peculiar by nature. From patient to patient, stent-related symptoms can vary from completely absent to moderately severe, and our treatment options are largely limited. Studies have shown that alpha-blockers (e.g. tamsulosin) reduce stent-related symptoms, and others have suggested that additional agents such as anticholinergics (e.g. oxybutynin) or urinary tract analgesics (e.g. phenazopyradine) may improve patient symptoms. Regardless, these authors investigated a mechanical advancement in stent material with aims of decreasing discomfort. While their findings were negative, this abstract can help guide subsequent trials aimed at reducing symptoms associated with the all-too-common problem of stent pain.

Max Kates, MD; Junior (U1) Resident

For me, the theme of this years AUA was personalized medicine.  Nowhere was this more apparent than with bladder cancer, where we are heading towards a treatment paradigm of therapy tailored towards  tumor biology.  The following 3 abstracts fit squarely in this trend.

MP28-14: Targeting HER2 with Trastuzumab-DM1 (T-DM1) in HER2-overexpressing bladder cancer.  Tetsutaro Hayashi*, Wolfgang Jaeger, Igor Moskalev, Shannon Awrey, Na Li, Ladan Fazli, Vancouver, Canada, Wataru Yasui, Akio Matsubara, Hiroshima, Japan, Peter Black, Vancouver, Canada

In this study, the authors first identified HER2 overexpressing bladder cancer cell lines and then tested whether an agent targeting Her-2 had antitumor effects.  Bladder cancer has multiple tumor pathways, and this study gave insight into the future of bladder cancer care, where patients will be tested for protein expression, and their treatments will then be tailored to their specific species of bladder cancer.

MP34-14: Targeting epidermal growth factor receptor using photoimmunotherapy in the treatment of bladder cancer.  Sam Brancato*, Piyush Agarwal, Bethesda, MD

This study also foreshadowed the way medicine, oncology, and bladder cancer care will be  managed in the long-run.  Specific cell surface receptors on the urothelium that were upregulated in bladder malignancy were targeted using a monoclonal antibody that is bound to a flourescent dye, and targets in this case EGFR receptor.  A very unique technology will be interesting to follow as it moves beyond preclinical data.

MP34-07: Differential Gene Expression In Responsive Versus Recurrent Non-muscle Invasive High-grade Urothelial Carcinomas After Induction BCG.  Philip Ho*, Daniel Willis, Houston, TX, Saad Aldousari, Kuwait, Kuwait, Charles Guo, Colin Dinney, Xifeng Wu, Ashish Kamat, Houston, TX

The implications of this study is the BCG failure should be able to be identified prior to treatment by understanding the tumor's biology.  Treatment can then be tailored towards non BCG treatments in these refractory groups.  Ultimately,the tumor will provide a therapeutic blueprint for what will work in treating the cancer.

Hiten Patel, MD; Incoming Urology Resident

PD34-09: Does Prostate Cancer Gleason Pattern 3 Lack the Potential for Metastasis? Michael Vacchio*, Bo Xu, Diana Mehedint, Christine Murekeyisoni, Gissou Azabdaftari, James Mohler, Eric Kauffman, Buffalo, NY

The study provides further evidence that Gleason pattern 3 prostate cancer defined by the 2005 International Society of Urological Pathology guidelines lacks metastatic ability. It is important to note that tertiary pattern 4 or 5 was excluded. Although 1 of 451 patients had distant metastasis at a mean of 76 months, blinded pathologist re-review led to upgrading of the patient's prostatectomy specimen to Gleason 7 (12 of 18 men with biochemical failure who had negative margins were also upgraded).


PD31-03: Statin use and Survival after prostate cancer diagnosis in the Finnish Prostate Cancer Screening Trial.  Teemu Murtola*, Tampere, Finland, Liisa Määttänen, Kimmo Taari, Helsinki, Finland, Teuvo Tammela, Anssi Auvinen, Tampere, Finland

A dose-response relationship in statin use and prostate cancer mortality was observed among 6,220 men diagnosed with prostate cancer in the screening trial. The magnitude comparing users and non-users was impressive (HR 0.33 (0.23-0.49)) and supports more research into the relationship in the future. That being said, it is important to consider what the practical financial and side effect implications would be if the eventual debate is on widespread statin use as a preventative measure for men without high cholesterol - a group where the benefit, if any, is likely to be much lower.

Farzana Faisal, Medical Student

I found these two abstracts most interesting because they got me thinking about the research we are doing at Hopkins on racial disparities in prostate cancer.

PD34-08: Disparities in survival for California men with prostate cancer more associated with socioeconomics than either race or insurance status. Chandrasekar T, Fish K, Evans C, White RD, Dall'Era M.

These authors looked at over 360,000 men with PCa in the California Cancer Registry and found that SES, more so than race or insurance status, was the most important predictor of cancer specific survival and overall survival for men with localized or regional disease. These findings seem to contradict what we are showing with the Hopkins cohort - that AA race increases the risk of adverse pathology and BCR. However, a closer look at their data shows that AA race was still an independent predictor of survival outcomes even after adjusting for SES and insurance, and thus can be taken together with our findings to support the role of race as a biological contributor to tumor aggression and disparities in AA men.

MP78-06: Surgeon volume and disparities in postoperative complications among black men. Ruhotina N, Konijeti R, Reese S, Chung BL, Kibel A, Trinh QD, Chang SL.

This study concluded that lower access to high volume surgeons may be responsible for the increased risk of major Clavien complications post-prostatectomy for AA men. It's interesting to think about this factor of surgeon experience in terms of the increased risk of adverse pathology seen in AA men at prostatectomy, especially positive margins. This particular abstract prompted our group to start investigating the role of surgeon proficiency as factor in margin status and perhaps racial disparities.

Jason Cohen, Medical Student

PD34-01: Comparison of radical treatment and mortality in patients with non-metastatic prostate cancer in England and USA.  Ashwin Sachdeva*, Jan van der Meulen, Mark Emberton, Paul Cathcart, London, United Kingdom.

I thought it was interesting to see the differences in outcomes based on the variations in screening and treatment approaches.  It is something we do not get to see and is difficult to study with our own populations.

PD31-04: Do Environmental Factors Modify the Genetic Risk of Prostate Cancer? Stacy Loeb*, New York, NY, Sarah Peskoe, Corinne Joshu, Baltimore, MD, Wen-Yi Huang, Bethesda, MD, Richard Hayes, New York, NY, H. Ballentine Carter, William Isaacs, Elizabeth Platz, Baltimore, MD

This was an interesting talk on things that are often heard in the lay literature, with some corresponding data.  It also looks like it would lead to many research possibilities.


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Read the entire abstracts:
For podium presentations (PD5-), click here.
For poster presentations (MP10-), click here.

AUA Highlights: Testis Cancer, by Dr. Pierorazio

Although a relatively rare malignancy, testis cancer affects approximately 9k men and boys each year.  While not as common or popular as some other urological malignancies, representation in the scientific sessions at the 2014 American Urological Association (AUA) Annual Meeting in Orlando, Florida was excellent.  Here are some of the thematic highlights, click on the links below to read the abstracts:

1. Access to care, epidemiological variation and cost-effectiveness in the treatment of testis cancer.

Because testis cancer is a rare disease, understanding of early symptoms, screening and access to health care can have huge implications regarding the treatment and eventual outcomes of disease.  The following presentations addressed some of these issues.  

In a study of nearly 6,000 men in the SEER (Surveillance, Epidemiology, End Results) database, uninsured men were more likely to present with advanced or metastatic disease, get radiation therapy if they had Seminoma (indicating advanced disease) and die of testis cancer.
PD5-02: The impact of lack of insurance on testicular cancer prognosis in young patients in the United States. Data from the SEER data base. Mohamed Kamel*, Mohammed Elfaramawi, Supriya Jadhav, Rodney Davis, Little Rock, AR.

In another study involving the National Cancer Database Registry, investigators from Vanderbilt University looked at compliance rates with the National Comprehensive Cancer Network (NCCN) Guidelines - which recommend serum tumor markers be drawn prior orchiectomy.  The authors found that young patients, low income patients, those treated at an academic center outside of the South or Midwest were more likely to be treated in compliance with the NCCN Guidelines.
MP10-03: The Influence of Access to Care on Adherence to Clinical Practice Guidelines for Testis Cancer.  C.J. Stimson*, Zachary Reardon, Nashville, TN, Sanjay Patel, Chicago, IL, Harras Zaid, Samuel Kaffenberger, Daniel Barocas, Matthew Resnick, Sam Chang, Nashville, TN

In a second study using the National Cancer Database Registry, researchers looked at over 75k men with testis cancer and found that non-Caucasian men had higher rates of advanced (Stage III) disease and worse overall survival.  African-American men had the highest rates of testis cancer-specific death.

MP10-05: Influence of race on outcomes in testicular cancer: Analysis of 75902 patients in the National Cancer Database.  Claudio Jeldres*, Craig R. Nichols, Khanh Pham, Seattle, WA, Sia Daneshmand, Los Angeles, CA, Christian Kollmannsberger, Vancouver, Canada, Brandon Hayes-Lattin, Portland, OR, Erika Wolff, Katherine Odem-Davis, Christopher R. Porter, Seattle, WA

In a cost-effectiveness analysis, researchers from Kansas City, Kansas examined the role of testicular self-examination in asymptomatic men.  Using Medicare reimbursements to estimate costs, they calculated that the cost of treating an advanced stage testis cancer was roughly $50k, while the costs of office evaluation ranged from $150-600, and the cost of an orchiectomy for early-stage disease is approximately $20k.  Therefore, they concluded - contrary to the recommendation of the US Preventative Services Task Forces (USPSTF) - that testicular self-examination is cost-effective and should not be discouraged.
MP10-11: TESTICULAR SELF-EXAMINATIONS: A COST ANALYSIS. Michael Aberger*, Bradley Wilson, Jeffrey Holzbeierlein, Tomas Griebling, Ajay Nangia, Kansas City, KS

2. Treatment of early stage disease.

The treatment of Clinical Stage 1 testis cancer is evolving (click here to see our blog on the treatment of clinical stage 1 NSGCT).  Most patients are cured with orchiectomy alone, and the remainder can be salvaged with chemotherapy and/or surgery.  Therefore active surveillance is emerging as the most common management strategy for these patients with primary retroperitoneal lymph node dissection (RPLND) and chemotherapy as second options.  However, given the young age and relatively good health of men with testis cancer, the long-term implications of each management strategy are not fully realized.  These presentations address this topic.

To investigate the use of active surveillance for Stage 1 testis cancer, researchers in this study used data from the 75k men in the National Cancer Database Registry with testicular cancer.  For Clinical Stage 1 Seminoma, they found the rates of active surveillance increased from 25% to 55% over the time period from 1998-2011 with a concomitant decrease in radiation from 72% to 28%.  Interestingly, for non-seminomatous germ cell tumors the rates of active surveillance remained stable (58-66%) while rates of primary chemotherapy increased (28%) and retroperitoneal lymph node dissection (RPLND) decreased (12.9%) in 2011.  However, in 2011, 50% of patients with cT1a disease received chemotherapy and not active surveillance.
PD5-04: United States trends in patterns of care in clinical stage I testicular cancer: Results from the National Cancer Data Base (1998-2011).  Claudio Jeldres*, Craig R. Nichols, Khanh Pham, Seattle, WA, Sia Daneshmand, Los Angeles, CA, Christian Kollmannsberger, Vancouver, Canada, Brandon Hayes-Lattin, Portland, OR, Erika Wolff, Katherine Odem-Davis, Christopher R. Porter, Seattle, WA

In a retrospective study of 48 men with clinical stage 1 seminoma on active surveillance, only 2 patients recurred giving a 95% recurrence free survival at 3 years.
MP10-06: Lower-Than-Expect Relapse Rate Among Contemporary Patients with Clinical Stage I Seminoma Managed on Surveillance.  Cesar Ercole*, Cleveland, OH, Estefania Linares, Madrid, Spain, Maria Mir, Yaw Nyame, Daniel Greene, Timothy Gilligan, Andrew Stephenson, Cleveland, OH

In an update of prospective, single arm, phase II clinical trial, 40 patients with high-risk clinical stage 1 non-seminomatous germ cell tumors received one cycle of BEP (Bleomycin, Etoposide and Cisplatinum chemotherapy).  With 15-years of follow-up, one patient recurred and died of metastases, three developed a contralateral testis tumor and three developed a secondary malignancy.
MP10-09: Fifteen years after treatment with one adjuvant cycle of Etoposide, Bleomycin and Cisplatin chemotherapy outcomes in patients with high risk nonseminomatous germ cell tumors clinical stage I. Extended follow up of a prospective single arm clinical trial cohort. Alvaro Vidal Faune*, George N. Thalmann, Martin Fey, Urs E. Studer, Bern, Switzerland

3. Retroperitoneal lymph node dissection (RPLND) for advanced (retrocrural) disease

While the overall survival rate for patients with testis cancer is excellent, after chemotherapy, some patients will develop chemotherapy-resistant teratoma that must be resected surgically.  One of the more challenging locations for a teratoma is behind the diaphragm in the retrocrural space.  At Johns Hopkins, we do these surgeries with either thoracic or vascular surgeons depending on the location and appearance of the tumor.

Two of the leading centers in the treatment of advanced testicular cancer, Indiana University and Memorial Sloan Kettering Cancer Center in New York, presented their experiences with retrocrural metastases.  In both series, the majority of tumors were teratoma.  A variety of incisions were described, with the most common being an abdominal approach with trans-diaphragmatic access when necessary.  Both centers prescribed to joint surgery involving both urology and thoracic surgery.  At Johns Hopkins, we do these surgeries with either thoracic or vascular surgeons depending on the location and appearance of the tumor.
PD5-05: SURGICAL MANAGEMENT OF RETROCRURAL DISEASE IN TESTIS CANCER: OUTCOMES AND EVOLUTION OF PRACTICE.  Hristos Kaimakliotis*, K Clint Cary, Jose Pedrosa, Timothy Masterson, Richard Bihrle, Kenneth Kesler, Richard Foster, Indianapolis, IN
PD5-06: Retrocrural dissection during retroperitoneal lymph node dissection for testicular cancer.  Itay Sternberg*, Brett Carver, Melanie Bernstein, Joel Sheinfeld, New York, NY

Read the entire abstracts:
For podium presentations (PD5-), click here.
For poster presentations (MP10-), click here.


Phillip M. Pierorazio, MD is the Director of the Division of Testicular Cancer at the Brady Urological Institute at Johns Hopkins.  

AUA Highlights: Infertility, by Dr. Rao

Male infertility was well represented at AUA (American Urological Association) Annual Meeting 2014 in Orlando, Florida. In the plenary session, the risks of increased paternal age were outlined. Notably, children of older fathers are at higher risk of autism, schizophrenia, and achondroplasia (dwarfism). Although the relative increase in incidence of these conditions is alarming, the overall incidence remains low, even in children of older fathers. (Click here to see the video of this Critical Discussion: Advanced Paternal Age - What Are the Real Risks?)

A topic that received continued attention is the increased use of testosterone. This is of particular importance for men with impaired fertility. Use of testosterone replacement therapy causes reversible infertility in most men, however some patients may not recover even after discontinuing the medication. It is critical that men with low testosterone and infertility should not be treated with testosterone replacement therapy, but other alternative medications should be considered instead.

Much research was presented on the outcomes after varicocele. Notably, a meta-analysis of previous studies showed an improvement in pregnancy and life birth rates after varicocele repair in couples using assisted reproductive techniques such as IVF and ICSI. In addition, successful sperm retrieval rates were higher in men who underwent extraction procedures after varicocele repair compared to men with untreated varicoceles. (PD24-01; see below)

In addition, many studies were presented that investigated various genes and DNA modifications that may play a role in infertility. However, none of these will cause immediate change in the treatment of infertile men. Currently, here at the Brady, we are collaborating with many Hopkins scientists to investigate molecular causes for infertility. These studies include finding unidentified genes causing infertility, investigating whether transposons are interrupting critical DNA sequences of sperm production, and identifying other molecules that may play roles and in male infertility treatment for male contraception.

This blog was written by Pravin Rao, M.D., Assistant Professor and Director of Reproductive Medicine and Surgery at the Brady Urological Institute at Johns Hopkins.

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PD24-01: The role of varicocele repair prior to assisted reproductive technology 

Saneal Rajanahally*, Houston, TX, Edgar Kirby, Karen Crowell, Robert Coward, Chapel Hill, NC

Abstract: PD24-01 

Introduction and Objectives 

While it has been established that varicoceles can contribute to infertility, and that varicocele repair (VR) can improve semen parameters such that fertility can be achieved, the relationship between VR and subsequent success with assisted reproductive technologies (ART) has yet to be definitively elucidated. This study is a systematic review the available literature describing the impact of VR on ART outcomes. 

Methods 

A PubMed search from 1/1982-9/2013 was performed to identify prospective, prospective-controlled, and retrospective studies addressing the relationship between VR and ART outcomes in couples with male factor infertility. Studies were excluded if they did not include fertilization, pregnancy, and/or live birth rates. Statistical analysis was performed using Fisher’s exact test. 

Results 

Seven studies were identified (1 prospective, 4 prospective controlled, 2 retrospective). Five of 7 studies utilized intracytoplasmic sperm injection (ICSI), 1 reported in vitro fertilization (IVF) outcomes, and 1 used intrauterine insemination (IUI). There was no difference in fertilization rate between surgical and non-surgical groups (67.8% vs 66.1%). However, 245 of 505 patients (48.5%) who underwent VR achieved pregnancy compared with 199 of 475 (41.9%) with untreated varicocele (p<0.05). Live birth rate was significantly higher after VR (n=314, 46.5%) in comparison to the uncorrected varicocele cohort (n=374, 32.1%, p<0.001). Pregnancy (11.8% vs. 6.3%, p<0.05) and live birth rate (11.8% vs. 2.1%, p<0.05) per IUI cycle were both significantly higher in patients after VR in comparison to those untreated. Individuals with non-obstructive azoospermia (NOA) had a significantly higher sperm retrieval rate after VR (n=140, 57.1%) than those with NOA and untreated varicocele (n=218, 38.9%, p<0.005). 

Conclusions 

Available data in this systematic review demonstrate a higher pregnancy and live birth rate in men after VR compared with those with uncorrected varicoceles, along with increased sperm retrieval rates in men with NOA. The positive impact that VR may have on ART outcomes should be discussed with couples with male factor infertility due to varicocele. 

Date & Time: May 19, 2014 3:30 PM-5:30 PM 

Session Title: Infertility: Therapy 

Sources of Funding: None 

AUA 2014 Outstanding Posters

The American Urological Association (AUA) Annual Meeting, 2014 has been a tremendous success for the Brady Urological Institute.  With greater than 60 faculty and research presentations over a five day period, members of the Brady team have been extremely busy sharing our discoveries with the world.  On Saturday, May 18, 2014, 36 presentations were awarded "Outstanding Poster" designations for the entire meeting in three categories: benign disease, oncology and research.  Brady researchers were awarded two Outstanding Poster Awards, which we share below:

OUTSTANDING POSTER #1

OP1-04: Identification and Validation of Protein Biomarkers of Response to Neoadjuvant Chemotherapy in Muscle Invasive Urothelial Carcinoma 

Alexander Baras*, Nilay Gandhi, Enrico Munari, Sheila Faraj, Mohammad Hoque, Mark Schoenberg, Trinity Bivalacqua, George Netto, Baltimore, MD

Summary: Neoadjuvant chemotherapy improves survival for patients undergoing radical cystectomy for muscle-invasive urothelial cancers of the bladder.  The greatest survival benefit is seen in those patients in whom all cancer is eradicated from the bladder (pT0).  However, the prognosis for patients who fail to respond to chemotherapy or progress while on chemotherapy is poor.  Predicting who will and will not respond to chemotherapy has huge importance in this area.  Researchers from Hopkins identified two genetic markers that could be identified from tissue obtained prior to chemotherapy, to assess the potential response to the medication.  Further studies are needed, however these data may help identify patients best served by chemotherapy and those who should forego chemotherapy for a rapid cystectomy.

Introduction and Objectives Neoadjuvant chemotherapy (NAC) results in 5-10% increase in 5-year survival rate in muscle invasive bladder cancer (MIBC) patients. More importantly, those who achieve a complete response (ypT0) have a 5 year survival rate of 80% as opposed to 40% for those who do not. However, NAC is not widely utilized due to concerns related to delay of cystectomy, potential side-effects, and inability to predict effectiveness. Recently suggested molecular signatures of chemoresponsiveness, which could prove useful in this setting, are yet to be translated into clinical practice. 
Methods mRNA expression data from a prior report on a NAC-treated MIBC cohort (Kato et. al) were analyzed in combination with the antibody database of the Human Protein Atlas (HPA). We identified classifier candidate biomarkers that can be detected by immunohistochemistry (IHC) in TURB biopsy material prior to NAC. The candidate biomarkers were subsequently validated in an independent cohort of 52 MIBC specimens. Response to NAC was defined as the lack of residual MIBC at cystectomy. 
Results By filtering based on large amplitude mRNA changes and the area under the receiver operator curve (AUROC), we identified 21 genes whose mRNA expression profiles differentiate response to NAC (n=33), Figure 1A. Using the HPA, we found that commercially available antibiodies to the protein products of 8 of these genes exhibited differential staining across a set of urothelial carcinomas cataloged in the HPA. In addition, 12 normal tissues were identified from the HPA that can serve as positive and negative controls for the 8 proteins. Our initial studies with 2 of these markers in a multivariate logistic regression model have yielded strong performance (80% accuracy) in identifying patients in our independent validation cohort that are not likely to benefit from NAC due to chemoresistance (Fischer’s exact test p-value 0.02), Figure 1B & 1C. 
Conclusions We illustrate the feasibility of translating gene expression signature data on NAC response into an IHC classifier applicable to TURB specimens. The performance achieved by the initial two markers in our study is being further characterized and the other putative protein markers are being assessed in our TMA cohort. 

OUTSTANDING POSTER #2

OP1-10: Rho-kinase inhibition prevents nNOS uncoupling in the MPG, erectile dysfunction and increases neuronal outgrowth following cavernous nerve injury 

Johanna Hannan*, Xiaopu Liu, Ahmet Hoke, Arthur Burnett, Trinity Bivalacqua, Baltimore, MD
Funding: NIH K08DK090370 and Urology Care Foundation.

Summary: Post-radical prostatectomy erectile dysfunction is a major issue faced by many patients and urologists today.  In order to potentially improve ED, inhibition of molecules that potentiate nerve injury, RhoA and RhoKinase (ROCK), an experimental medication was given to rats with a nerve injury.  This experiemental medication, U-27632, a ROCK inhibitor, improved post-nerve injury erectile function by preventing nitric oxide degeneration and promoting nerve regrowth and regeneration.  This may be a medication suitable to prevent post-prostaetectomy ED in the future.

Introduction and Objectives RhoA and Rho-kinase (ROCK) are implicated in the inhibition axonal growth/neurite sprouting, and neurodegeneration via regulation of inflammation and apoptosis following peripheral nerve injury. We hypothesize that degeneration of the cavernous nerve (CN) after injury is due to increased RhoA/ROCK signaling in the major pelvic ganglion (MPG) leading to neuronal nitric oxide synthase (nNOS) uncoupling and nerve degeneration. This study aimed to characterize the role of ROCK inhibition in preserving erectile responses, penile contractions, nNOS uncoupling and neurite outgrowth following bilateral cavernous nerve injury (BCNI). 
Methods Male Sprague-Dawleys rats (12 wks) were separated into sham, BCNI and BCNI treated with Y-27632 (ROCK inhibitor, 5 mg/kg twice daily; n=8/group). 14 days after BCNI, groups underwent CN stimulation to determine erectile function. Penes were dissected and contractile responses to phenylephrine (PE) and electrical field stimulation (EFS) were assessed. MPGs were excised and protein (Western blots) and gene expression (q-PCR) of nNOS and growth associated protein 43 (GAP43) were assessed. Additional MPGs (n=3/group) were cultured in reduced growth factor matrigel for 48h and neurite growth was measured. 
Results While erectile function was severely decreased in BCNI rats, daily administration of Y-27632 improved erections 2-fold (p<0.05). nNOS MPG gene expression was decreased by 50% after BCNI and recovered to sham levels with Y-27632 (p<0.05). nNOS uncoupling was increased in BCNI MPGs and completely prevented in y-27632 treated rats (p<0.05). Cavernous contractile responses to PE were unchanged. EFS-mediated penile contractions were significantly lower following BCNI and treatment with Y-27632 increased EFS-mediated contractions 2-fold compared to sham and BCNI penes (p<0.05). MPG neurite outgrowth was unchanged in sham and BCNI; however, BCNI+Y MPGs had significantly increased growth (S:328±9μm; BCNI:349±14μm; BCNI+Y:405±11μm, p<0.05). GAP43, a growth protein highly expressed during axonal regeneration, was increased 25% following BCNI and 30% with Y-27632 treatment indicating treatment increased axonal growth. 
Conclusions Inhibition of ROCK preserved erections, prevented nNOS uncoupling, mediated increased neurite growth and increased nerve-mediated penile contractions in BCNI rats. Preventing the activation of RhoA/ROCK signaling in the MPG and CN after injury may inhibit neurodegeneration and post-radical prostatectomy erectile dysfunction. 


For more Brady Urological Presentations, visit the AUA2014 Website or stay tuned.