Analysis of the AUA Guidelines: Strength of Evidence Correlates With Recommendation Levels.

INTRODUCTION: As part of its mission to provide the highest standards of clinical care, the AUA publishes guidelines on numerous urological topics. We sought to evaluate the caliber of evidence used establish the currently available AUA guidelines. METHODS: All available AUA guideline statements in 2021 were reviewed for their level of evidence and recommendation strength. Statistical analysis was performed to identify differences between oncological and nononcologic topics, and statements pertinent to diagnosis, treatment, and follow-up. A multivariate analysis was utilized to identify factors associated with strong recommendations. RESULTS: A total of 939 statements across 29 guidelines were analyzed; 39 (4.2%) were backed by Grade A evidence, 188 (20%) Grade B, 297 (31.6%) Grade C, 185 (19.7%) Clinical Principle, and 230 (24.5%) Expert Opinion. There was a significant association of oncology guidelines (6% vs 3%, P = .021) with more grade A evidence and less Grade C Evidence (24% vs 35%, P = .002). Statements pertaining to diagnosis and evaluation were more likely backed by Clinical Principle (31% vs 14% vs 15%, P < .01), treatment statements backed by B (26% vs 13% vs 11%, P < .01) and C (35% vs 30% vs 17%, P < .01) grade evidence, and follow-up statements backed by Expert Opinion (53% vs 23% vs 24%, P < .01). On multivariate analysis, strong recommendations were more likely supported by high-grade evidence (OR = 12, P < .01). CONCLUSIONS: The majority of evidence for the AUA guidelines is not high grade. Additional high-quality urological studies are needed to improve evidence based urological care.

Ureteral injury after posterior spinal fusion.

Entry into the retroperitoneal space during Minimally Invasive Transforaminal Lumbar Interbody Fusion (MI-TLIF) presents a rare possibility of iatrogenic ureteral injury. Rare complications of ureteral injury after previous open posterior spinal surgery have been reported however there is a paucity of reports after a minimally invasive technique. We now describe a case of ureteral injury after MI-TLIF.

Medicaid Patients Experience Longer Wait Times at Academic Urology Clinics Compared to Patients with Medicare.

INTRODUCTION: It has been established that Medicaid patients face unequal access to health care. There is a paucity of literature comparing wait times for Medicaid patients to those of patients with other types of insurance. We determined whether Medicaid patients experience longer wait times at academic urology clinics compared to patients with Medicare. METHODS: A prospective cross-sectional telephone survey was conducted in October 2016. The study involved collection of data from multiple academic centers with telephone interviews conducted from a single institution. Calls were made to all accredited urology residency programs (131). Earliest appointment times were established for fictional patients with Medicaid and then Medicare. The main outcome was the difference in wait times for a new patient appointment in a urology clinic for Medicaid vs Medicare patients. The wait time in days was the difference between the date of the appointment and the date of the telephone call. RESULTS: There were 108 academic urology clinics that accepted Medicaid and Medicare patients in our final analysis (82.4% participation rate). A 2-tailed t-test was performed with unequal variances for the wait times between Medicaid and Medicare groups. There was a significant difference (p <0.001) between mean wait times for a patient with Medicare (23 days, SD 20.8; 95% CI 19.0, 26.9) vs Medicaid (35 days, SD 27.5; 95% CI 30.0, 40.3). CONCLUSIONS: Our data suggest that Medicaid patients experience longer wait times for their initial outpatient urological evaluation. These findings may be used for future health policy considerations.

Diagnosis of bladder cancer with microelectromechanical systems-based cystoscopic optical coherence tomography.

OBJECTIVES: To examine the utility and potential limitations of microelectromechanical systems-based spectral-domain cystoscopic optical coherence tomography (COCT) so as to improve the diagnosis of early bladder cancer. METHODS: An optical coherence tomography catheter was integrated into the single instrument channel of a 22F cystoscope to permit white-light-guided COCT over a large field of view (4.6 mm wide and 2.1 mm deep per scan at 8 frames/s) and 10-microm resolution. Intraoperative COCT diagnosis was performed in 56 patients, with a total of 110 lesions examined and compared with biopsied histology. RESULTS: The overall sensitivity of COCT (94%) was significantly higher than cystoscopy (75%, P = .02) and voided cytology (59%, P = .005); the major enhancement over cystoscopy was for low-grade pTa-1 cancer and carcinoma in situ (P < .018). The overall specificity of COCT (81%) was comparable to voided cytology (88.9%, P = .49), but significantly higher than cystoscopy (62.5%, P = .02). CONCLUSIONS: The microelectromechanical systems-based COCT, owing to its high resolution and detection sensitivity and large field of view, offers great potential for "optical biopsy" to enhance the diagnosis of nonpapillary bladder tumors and their recurrences and to guide bladder tumor resection.

Functional phenotyping and genotyping of circulating tumor cells from patients with castration resistant prostate cancer.

Circulating tumor cells (CTCs) hold promise for studying advanced prostate cancer. A functional collagen adhesion matrix (CAM) assay was used to enrich CTCs from prostate cancer patients' blood. CAM ingestion and epithelial immuno-staining identified CTCs, which were genotyped using oligonucleotide array comparative genomic hybridization. The highest CTC counts were observed in men with metastatic castration resistant prostate cancer (CRPC) compared to castration sensitive prostate cancer. Copy number profiles for CRPC CTCs were similar to paired solid tumor DNA, and distinct from corresponding DNA from the residual CAM-depleted blood. CAM CTC enrichment may allow cellular and genetic analyses in prostate cancer.

Deficits in urological knowledge among medical students and primary care providers: potential for impact on urological care.

PURPOSE: Recent data indicate a decline in the urological education of third and fourth year medical students. To determine if this decline has an impact on the treatment of patients we performed a survey to evaluate the general level of knowledge, attitudes and practices with regard to common urological issues seen in a general medical practice among medical students and faculty involved in primary care at an academic institution. MATERIALS AND METHODS: A confidential questionnaire was distributed to attendings, residents and fellows, and the clinical medical students at our academic institution to ascertain how they evaluate and treat patients with common urological complaints. All responses were entered into SPSS statistical software. RESULTS: A total of 300 surveys were distributed, 150 of which were returned with complete information for data analysis. Knowledge with regard to various conditions including hematuria, recognition of an age specific abnormality in serum prostate specific antigen and overactive bladder was low for all groups. Furthermore, respondents demonstrated a low likelihood of requesting formal urological evaluation for these conditions. Exposure to a urology elective in medical school had a positive impact on some areas of urological evaluation. CONCLUSIONS: General urological knowledge with regard to the primary care setting is insufficient. The potential for impact on patient care is enormous. These data highlight the need for a definitive urological curriculum in medical school as well as continued education at the resident and faculty level with regard to evaluation, management and recognition of when to request formal urological evaluation in the primary care setting.

Wilm's tumor during pregnancy: report of laparoscopic removal and review of literature.

Wilm's tumor, or nephroblastoma, is a common renal tumor among children. Few cases of Wilm's tumor have been reported in women during pregnancy. The authors present a rare case of a pregnant female, who underwent laparoscopic excision of a large Wilm's tumor. The authors have also provided a review of the current literature.

Are patients aware of the association between smoking and bladder cancer?

PURPOSE: Smoking is the single greatest risk factor for bladder cancer. Since few studies have demonstrated the efficacy of screening for bladder cancer, primary prevention by decreasing the modifiable risk factors is the best defense. An aspect of modifying a behavioral risk factor is awareness of the association between behavior and disease. While many anti-smoking campaigns specifically focus on lung cancer, few mention bladder cancer. We evaluated the awareness of smoking as a risk factor for bladder cancer. MATERIALS AND METHODS: Between February and May 2005 we prospectively surveyed patients presenting to a urology clinic regarding their knowledge of risk factors for bladder cancer and other cancers. The questionnaire also captured data regarding patient smoking habits. RESULTS: A total of 280 patients completed the survey, including 34% who were younger than 50 years, 63% who were male, 89% who were white and 57% who were college graduates. Only 36% vs 98% of the sample reported that smoking was a risk factor for bladder vs lung cancer. Patients with a higher level of education and females were statistically more likely to be aware of the association between smoking and bladder cancer. CONCLUSIONS: Patients at a urology clinic had low overall knowledge regarding bladder cancer risk factors. Most patients queried had no idea regarding the relationship between bladder cancer and tobacco use regardless of smoking status. Our study suggests the need for the American public to be better educated to help combat smoking related cancers.

Noninvasive detection of prostate cancer by quantitative analysis of telomerase activity.

PURPOSE: Prostate cancer is the most common male malignancy and the second leading cause of male cancer death; therefore, there is urgent necessity for noninvasive assays for early detection of prostate cancer. Obtaining prostate tumor samples surgically is problematic because the malignancy is heterogeneous and multifocal and early-stage tumors are nonpalpable. In contrast, exfoliated cells represent the cancer status of the entire gland better due to the general tendency of cancer cells to exfoliate into biological fluids. The purpose of this study was to clarify whether quantitative analysis of telomerase activity in exfoliated cells in urine could serve as a reliable molecular marker of prostate malignancy. EXPERIMENTAL DESIGN: We analyzed prospectively post-prostatic examination-exfoliated cells from the urine of 56 patients undergoing routine prostate screening. Epithelial cells were isolated and enriched by immunomagnetic separation. Telomerase activity was analyzed by quantitative real-time PCR telomeric-repeat amplification protocol assay using Opticon MJ research instrument. RESULTS: We report now that all prostate cancer patients revealed high levels of telomerase activity thereby showing 100% of the assay sensitivity. In contrast, the majority of patients with clinically confirmed benign prostatic hyperplasia (BPH) did not express any telomerase activity (70% of all BPH patients), most likely presenting cancer-free cases, or expressed low levels of activity (18%). However, about 12% of BPH patients revealed high levels of telomerase activity that potentially can reflect hidden prostate cancer. CONCLUSIONS: We suggest that the quantitative analysis of telomerase activity can be useful for the selection of prostate cancer and cancer-free cases.

Membrane type 1-matrix metalloproteinase promotes human prostate cancer invasion and metastasis.

Development of metastases requires cancer cells to breach underlying basement membrane, migrate through interstitial stroma and gain access to blood or lymphatic vessels. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been linked with these processes. Expression of MT1-MMP in human prostate cancer correlates with the stage of this disseminated disease. The mechanism underlying this observation, however, still remains to be understood. To study the role of MT1-MMP in prostate cancer dissemination, endogenous and recombinant MT1-MMP expressed in human prostate cancer cell lines (DU-145 and LNCaP) were examined. Using FITC-labeled Matrigel, a soluble basement membrane extract coated coverslips, LNCaP cells stably expressing a chimera of MT1-MMP and Green Fluorescent Protein (MT1-GFP) degraded Matrigel and readily migrated over degraded substrates. The degradation of Matrigel by LNCaP cells expressing MT1-GFP was sensitive to MMP inhibitors, CT-1746 and TIMP-2, but not TIMP-1. Cell migration was dramatically enhanced by expression of MT1-MMP. By employing surgical orthotopic implantation of LNCaP cells stably expressing MT1-GFP into the prostate gland of immunodeficient mice, we demonstrated that MT1-MMP promotes lymph node and lung metastasis of prostate cancer cells. Together, these results emphasize the pivotal role of MT1-MMP in prostate cancer dissemination and confirm that MT1-MMP is a suitable target to prevent cancer metastasis.

Prostate cancer cell adhesion to bone marrow endothelium: the role of prostate-specific antigen.

Bone metastasis is the most frequent complication of prostate cancer (PC). Elucidation of the biological basis of this specificity is required for the development of approaches for metastatic inhibition. We investigated the possibility that the preferential attachment of PC cells to bone marrow endothelium (as opposed to endothelium from other organs) affects this specificity. We selected, from peptide phage-displayed libraries, peptide ligands to surfaces of PC cells (C4-2B) attenuated (30-40%) binding of C4-2B cells to bone marrow endothelial cells (BMECs). We then determined the molecules on the surface of C4-2B cells interacted with the selected peptides using column affinity chromatography and a cDNA expression phage-displayed library generated from C4-2B cells in T7 phage. We identified a phage from the cDNA library that specifically bound to one of the selected peptides-L11. This phage displayed the amino acid sequence homologous for the COOH-terminal portion of prostate-specific antigen (PSA). To examine the possible direct involvement of PSA in the interactions between PC and BMECs, we performed a cell-cell adhesion assay. Antibodies to PSA attenuated PC cells adhesion to BMECs. In addition, exogenous proteolytically active PSA modulated this adhesion. Finally, inactivation of mRNA coding PSA by a small interfering RNA (siRNA) diminished C4-2B cell adhesion to BMECs. These results indicate that PSA expressed as secreted and surface-associated molecules in C4-2B cells is involved in cell-cell interactions and/or digests components of bone marrow endothelium for preferential adhesion and penetration of PC cells. The suggested experimental approach is a promising strategy for identification of cell surface molecules involved in intercellular interactions.