Research goals for the Division of Urology are to engage in investigations which have promise to move the field of urology forward. We also use our research efforts to educate our medical students, urology residents and research fellows on the importance of medical research and the proper way to develop and execute a research project. Some of our areas of interest are listed below:
- Prostate Imaging
- Prostate Cancer Active Surveillance
- Metabolomic Signature of Bladder Cancer
- Effect of Ketogenic Diet on Metabolomics of Prostate Cancer
- Catheter Associated Urinary Tract Infection
- Urologic Information Media
- Gender Disparities in Urology
David B. Leeser, MD
An Assessment of Humacyte's Human Acellular Vessel in Patients Needing Renal Replacement Therapy (HUMANITY)
- Sponsor: CTI Clinical Trial and Consulting Services
A prospective observational cohort study of patients with castration-resistant prostate cancer (CRPC) in the United States
The purpose of this prospective, observational study is to improve scientific understanding of prostate cancer patients with castration-resistant disease and the treatment patterns, quality of life and health care resources and costs associated with its management. This is a prospective, observational multi-center study of patients with CRPC in the United States.
- Sponsor: Astellas Pharma Global Development, Inc
Exploration of Host & Microbiological Biomarkers in Catheterized Urine Samples
Catheter-Associated Urinary Tract Infections (CAUTIs) are a significant healthcare problem resulting in significant morbidity, healthcare costs, and growing antibiotic resistance. The diagnosis of CAUTI is challenging due to limitations of current diagnostic testing and variable clinician judgment resulting in misdiagnosis and overtreatment. Enhanced diagnostic tools are needed to optimize CAUTI management. The host and urinary biomarkers associated with the development of CAUTI are poorly understood. Identification of biomarkers associated with CAUTI can provide further targets for preventative and diagnostic tools. To accomplish this, our group will utilize clinical urine samples from catheterized patients to identify candidate biomarkers that correlate with clinical CAUTI and are inversely correlated with uninfected patients. The identification of the array of biomarkers that are predictive of CAUTI will be a significant advancement, providing information for enhancing precision in clinical diagnostics for hospital-acquired-infections. Further studies will utilize candidate biomarkers of CAUTI in an integrated microfluidic sensor-treatment system designed to accurately sense colonization and potential biofilm formation. Ultimately biomarker exploration and the development of multimodal monitoring systems will enable comprehensive, real-time assessment of urine in catheterized patients. This offers opportunities for prevention, diagnosis, and effective as well as timely CAUTI intervention which is superior to that of current diagnostic techniques with implications for reduction in the misdiagnosis of CAUTI, inappropriate antibiotic use resulting in an increase in antimicrobial resistance and limited treatment options.
- Funding: American Urological Association Research Scholar Grant, UMB Institute for Clinical and Translational Research Accelerated Translational Incubator Collaboration Pilot Grant
Handheld point-of-care device to detect impending Catheter-Associated Urinary Tract Infection (CAUTI)
Indwelling bladder catheters quickly become colonized with bacteria, resulting in chronic asymptomatic bacteriuria (ASB) that is not indicative of infection. Catheters can also act as foci for catheter-associated urinary tract infection (CAUTI). Unfortunately, existing tests such as urine culture confuse ASB with true infection, leading to excessive use of antibiotics and rapid selection of resistant bacterial strains. With this project we are evaluating a handheld device that analyzes light passing through fluid-containing tubing in patients with a chronic indwelling catheter, without directly contacting fluid; the device has shown promise for optically differentiating CAUTI from ASB using sophisticated signal analysis algorithms.
- Funding: Maryland Innovation Initiative Application 2019-MII-5206
Improved detection of prostate cancer by integrating imaging
Our research group has been advancing the ability to more accurately detect and risk stratify prostate cancer by the integration of cutting-edge MRI and image-guided diagnostic tools such as MR/US fusion biopsy and robotic guided transperineal targeted biopsy. We have published extensively on this topic including in journals such as JAMA, New England Journal of Medicine, Journal of Clinical Oncology, Journal of the National Cancer Institute, and Lancet Oncology. We have demonstrated that integration of MRI and targeted biopsy improves the detection of aggressive prostate cancer by 30% as well as can dampen the unnecessary detection and potential overtreatment of clinically indolent tumors. The implications of these findings can impact improved ability to safely place patients on active surveillance, provide focal therapy, and cater treatment for aggressive cancer. We’re now researching how to take imaging-informed prostate cancer management to the next level by integrating AI into decision-making, using imaging for potential treatments such as focal therapy, examining advanced robotics guided by imaging, and evaluating the use of 3D printing as part of clinical care: We’re also studying in a national, NIH funded study how imaging can address racial disparities related to prostate cancer outcomes.
- Funding: NIH-National Insitutes of Health; DOD-Department of Defense
Prioritization of CER/PCOR on Prostate Cancer Active Surveillance: Community Consensus Initiative
Men newly diagnosed with localized prostate cancer (PCa) who have a low-risk disease profile are candidates for Active Surveillance (AS), the process of close monitoring in deferral of treatment if cancer progresses. AS avoids overtreatment and complications associated with prostate cancer therapy. Despite overwhelming support in national and international clinical guidelines, less than half of all eligible men initially opt for AS. Additionally, some men who do pursue AS eventually discontinue it in favor of treatment, despite no evidence of disease progression. The our group in collaboration with the PATIENTS Program at the University of Maryland Baltimore (UMB) seeks to begin addressing these unanswered Community Engaged Research (CER)/ Patient Centered Outcomes Research (PCOR) questions by bringing communities together, discussing AS challenges, and identifying areas of future research impactful to patients and physicians alike.
The proposed solution is convening members of key stakeholder communities, patients, spouses, caregivers, urologists, etc. to initiate a collaborative process to ensure appropriate focus (nationally and internationally) on immediate, shorter-term research initiatives. The initiative is designed to generate a prioritized list of unanswered questions in the PICOT (Population, Intervention, Comparison, Outcome, and Time) format that will facilitate meaningful future CER/PCOR centered on men with low-risk PCa. We are in the process of organizing and leading a national focused conference on this topic to address this issue.
- Funding: PCORI
Assessment of Patient Tolerance for Risk Associated with High Intensity Focused Ultrasound (HIFU) for the Ablation of Prostate Tissue
Patients living with prostate cancer have a unique perspective that informs choice about medical care. The goal of this research study is to assess patients’ perspectives on the benefits and risks associated with HIFU. Eligible prostate cancer patients will be identified and recruited from the University of Maryland Medical Center and surveyed regarding their understanding and opinions on prostate cancer management options. The survey tool was developed by the FDA research team based on literature review, interviews and publicly available data submitted to the FDA. The information obtained from this partnership with patients may help inform the FDA’s decision making for new prostate ablation devices.
- Funding: FDA-Food and Drug Administration
Using metabolomic signatures for risk-stratification and personalized treatment of bladder cancer
All cells in the body utilize metabolism to convert nutritional sources, such as fat, protein or carbohydrates, into energy and cellular building blocks for the tissues to grow and survive. It has been well understood that cancer cells not only require a higher rate of metabolism, or nutritional turnover, to survive and grow uncontrollably, but that the way cancer cells metabolism functions is different than normal cell metabolism. In bladder cancer, tumors tend to favor sugars such as glucose, and more aggressive tumors tend to be more reliant on this source. We utilize this information to study the role that the study of cellular metabolism, known as metabolomics, can help guide and improve the diagnosis and treatment of bladder cancer. Specifically, in this project we believe that understanding how cancer cell metabolism is functioning can give us insight as to how aggressive that cancer is. Furthermore, changes in metabolism due to treatments such as chemotherapy can provide early insights as to how the cancer is responding to that treatment. Such insight may be able to provide a significant early insight into how likely certain treatments are likely to be for individual tumors. Traditionally, the effectiveness of a chemotherapy is measured by starting treatment and waiting a few weeks to months to see if the tumors are shrinking. By utilizing cancer metabolomics, the early insight into cancer metabolic function may allow for more rapid decision making and moving on from ineffective treatments sooner.
- Funding: DOD, Maryland Industrial Partnerships Grant
Effect of ketogenic diet on the metabolomics profile on weight loss and PSA prostate-specific antigen of overweight prostate cancer patients on active surveillance
Men with indolent forms of prostate cancer are managed expectantly using active surveillance, with a goal of delaying treatment and its deleterious side effects. However, up to one-third of men experience progression with this approach and require treatment. Elevated body mass index (BMI) levels are associated with dramatically increased risk of such disease progression to prostate cancer. Therefore, we plan to conduct a feasibility study examining the utility of a 2-month ketogenic diet to stimulate weight loss as a potential approach in reducing the risk of cancer progression during active surveillance. We also hope to utilize this intervention time period as a window for collection of clinical data that may elucidate the mechanisms behind the benefits of weight loss in this setting.
- Funding: Nutrition Obesity Research Center (NORC)
Metabolic imaging of hyperpolarized [2-13C]pyruvate for improved diagnosis and risk-stratification of prostate cancer
Prostate cancer (PCa) is the second leading cause of cancer death in men; however most men with PCa will ultimately die of other causes. This has lead to the issue that since the treatment for prostate cancer carries significant complication risks with it as well, the risks of over treating men who would have died of other causes had they not been treated has to be weighed against the risks of undertreating those men who are risk of death from prostate cancer. Until recently, the most reliable methods to differentiate such men with low-risk versus high-risk disease was with the use of a physical exam, the blood test PSA, and biopsy results from the prostate. Such information was of benefit, but still lead to many men in whom the benefit from treatment remains uncertain. An emerging area of research is the study of cancer metabolism. It is believed by many that a better understanding of how cancer cells metabolize nutrients to survive will improve our ability to differentiate aggressive tumors from indolent ones. Tumor cells utilize energy sources such as sugars, fats, and protein (glucose, fatty acids, and amino acids) to generate energy and cellular building blocks for growth. It turns out that the way tumors utilize these energy sources is different than the way normal cells use these energy sources. The premise behind this study is to study how prostate cancer uses a specific energy source, pyruvate, and to understand how this utilization varies between benign tissues and indolent tumors versus aggressive tumors. It is our hypothesis that by understanding how tumors use pyruvate, specifically a particular nuclear labeled pyruvate with a heavy carbon atom on carbon two, [2-13C]pyruvate, we will better be able to differentiate aggressive from indolent prostate cancer. To perform these studies in the first aim of this study, prostate cells will be studied in the cell culture setting to examine how cells of varying aggressiveness metabolize [2-13C]pyruvate. Furthermore, specialized instruments will measure how the cells produce waste products of metabolism (lactic acid) as well as take in oxygen to maintain their metabolism.
- Funding: American Cancer Society; DOD-Department of Defense ; NIH-National Institutes of Health