Stephen J. Savage

Fluorescence in situ hybridization for detecting transitional cell carcinoma: implications for clinical practice.

To determine the diagnostic sensitivity of genetic studies using fluorescence in situ hybridization (FISH) for detecting both new and recurrent cases of transitional cell carcinoma (TCC) in a routine clinical practice setting, as bladder cancer has a significant risk of recurrence and progression to invasive disease and thus sensitive surveillance testing is very important.

Contemporary diagnosis and management of squamous cell carcinoma (SCC) of the penis

Whats known on the subject? and What does the study add?

Laparoscopic Cryoablation of Renal Masses: Which Lesions Fail?

OBJECTIVE To identify potential predictive characteristics of lesions which failed in laparoscopic renal cryoablation (LRC). We analyzed 47 lesions that underwent this approach. METHODS We reviewed 45 consecutive patients who underwent LRC of a renal mass between 2003 and 2008 at a single institution. A total of 47 masses were identified; all were treated by 2 surgeons. We analyzed patient age, ASA, pre- and postoperative creatinine, tumor size, location, number of cryoprobes used, and histology of the lesions. We reviewed imaging to identify characteristics of those lesions which failed LRC management, defined as lesions that demonstrated persistent enhancement and/or did not decrease in size within 6 months of therapy. RESULTS A total of 47 lesions in 45 patients were identified. The median follow-up was 13 months. Mean lesion size was 2.7 cm (range, 1.2-5.4), with 25 anterior and 22 lateral or posterior lesions. Of the biopsy samples from 40 of 47 lesions, renal cell carcinoma was found in 23, oncocytoma was found in 7, and 10 were benign or inconclusive. Treatment failure was noted in 8 of 47 lesions (17%), 7 of which (87.5% of failed lesions) had broad-based contact with the renal sinus. Broad-based lesions which made contact with the renal sinus were successfully treated 53.3% of the time, whereas lesions which lacked contact with the renal sinus were treated successfully 96.9% of the time (P <.01). CONCLUSIONS Broad-based central location of a renal mass may predict a significantly increased risk of failure of LRC and should be considered in patient counseling.

Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Trial

OBJECTIVE To evaluate asymptomatic men with elevated serum prostate-specific antigen (PSA) to determine whether a 6-week course of fluoroquinolone antibiotics lowers serum PSA and affects recommendations for prostate biopsy. MATERIALS AND METHODS A randomized, single-center prospective trial of 150 men with an initial elevated PSA was conducted. Patients were randomized to 6 weeks of ciprofloxacin or observation. Those patients with persistently elevated PSA were recommended to proceed with transrectal ultrasound-guided 12-core biopsy. Those with reduced PSA were offered transrectal ultrasound-guided biopsy but could opt to continue serial digital rectal examination/PSA. Patients were followed an average of 4.6 years to assess trends in PSA and biopsy results. RESULTS Of 136 men who completed the trial, 63 were in the treatment and 73 were in the observation group. The average PSA change from baseline was borderline statistically significant with a change of -0.68 ng/mL in the treatment arm and 0.01 ng/mL in the observation arm (P  =  .052). Of those who underwent biopsy, prostate cancer was diagnosed in the first biopsy in 24 (63%) of the treatment vs 27 (52%) of the observation group (P  =  .60) over follow-up. CONCLUSION In a cohort of asymptomatic men with elevated PSA, there was only a borderline statistically significant change in serum PSA between patients randomized to a 6-week course of fluoroquinolones vs observation, and there was no difference in positive prostate biopsy results. Our clinical recommendation is one should not treat patients with elevated serum PSA with antibiotics in the absence of clinical symptoms of prostatitis.

A Multi-Institutional Prospective Trial Confirms Noninvasive Blood Test Maintains Predictive Value in African American Men

Purpose: The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. Materials and Methods: Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. Results: Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. Conclusions: The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men.

A Multi-institutional Prospective Trial in the Veterans Affairs Health System confirms the 4Kscore maintains its Predictive value among African American Men

Purpose: The 4Kscore® test accurately detects aggressive prostate cancer and reduces unnecessary biopsies. However, its performance in African American men has been unknown. We assessed test performance in a cohort of men with a large African American representation. Materials and Methods: Men referred for prostate biopsy at 8 Veterans Affairs medical centers were prospectively enrolled in the study. All men underwent phlebotomy for 4Kscore test assessment prior to prostate biopsy. The primary outcome was the detection of Grade Group 2 or higher cancer on biopsy. We assessed the discrimination, calibration and clinical usefulness of 4Kscore to predict Grade Group 2 or higher prostate cancer and compared it to a base model consisting of age, digital rectal examination and prostate specific antigen. Additionally, we compared test performance in African American and nonAfrican American men. Results: Of the 366 enrolled men 205 (56%) were African American and 131 (36%) had Grade Group 2 or higher prostate cancer. The 4Kscore test showed better discrimination (AUC 0.81 vs 0.74, p <0.01) and higher clinical usefulness on decision curve analysis than the base model. Test prediction closely approximated the observed risk of Grade Group 2 or higher prostate cancer. There was no difference in test performance in African American and nonAfrican American men (0.80 vs 0.84, p = 0.32), The test outperformed the base model in each group. Conclusions: The 4Kscore test accurately predicts aggressive prostate cancer for biopsy decision making in African American and nonAfrican American men.

ACR Appropriateness Criteria® Renovascular Hypertension

Renovascular hypertension is the most common type of secondary hypertension and is estimated to have a prevalence between 0.5% and 5% of the general hypertensive population, and an even higher prevalence among patients with severe hypertension and end-stage renal disease, approaching 25% in elderly dialysis patients. Investigation for renal artery stenosis is appropriate when clinical presentation suggests secondary hypertension rather than primary hypertension, when there is not another known cause of secondary hypertension, and when intervention would be carried out if a significant renal artery stenosis were identified. The primary imaging modalities used to screen for renal artery stenosis are CT, MRI, and ultrasound, with the selection of imaging dependent in part on renal function. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Clinical Utility of Concurrent Single-Nucleotide Polymorphism Microarray on Fresh Tissue as a Supplementary Test in the Diagnosis of Renal Epithelial Neoplasms

OBJECTIVES The histologic and immunohistochemical variability of renal epithelial tumors makes classification difficult; with significant clinical implications, efforts to make the proper diagnoses are necessary. Single-nucleotide polymorphism (SNP) microarray analysis has been proposed as a supplementary study for the classification of renal epithelial neoplasms; however, its practical use in the routine clinical setting has not been explored. METHODS Surgical pathology cases that were classified histologically as renal epithelial tumor subtypes and had concurrent SNP microarray were retrospectively reviewed to correlate tumor morphology and SNP microarray results. RESULTS Of the 99 cases reviewed, 88 (89%) had concordant histologic and microarray results. Four (4%) cases were unclassifiable by microarray due to uncharacteristic chromosomal abnormalities. Seven (7%) of the 99 cases had discordant microarray and histologic diagnoses, and following review of the histology, the diagnoses in two of these cases were subsequently changed. CONCLUSIONS For most cases, concurrent SNP microarray confirmed the histologic diagnosis. However, discrepant microarray results prompted review of morphology and further ancillary studies, resulting in amendment of the final diagnosis in 29% of discrepant cases. SNP microarray analysis can be used to assist with the diagnosis of renal epithelial tumors, particularly those with atypical morphologic features.

Castration-Resistant Prostate Cancer: Sequencing Oral and Infusion Agents

Purpose of ReviewTo update treatment options and considerations for castration-resistant prostate cancer with specific attention to sequencing of agents based on available evidence and treatment rationale.Recent FindingsThe newest research developments over the last several years include multicenter studies that address the sequencing of therapies to improve the treatment of metastatic castration-resistant prostate cancer. Chemotherapy agents, as well as androgen receptor antagonists, are evolving, and there are new tests available to define which patients are more likely to benefit. In addition, there have been some additional trials looking into the safety and efficacy of combination treatment and new therapies.SummaryThere are multiple factors that should be considered to determine the sequence and/or combinations of therapies for metastatic castration-resistant prostate cancer that can improve quality of life and survival. Promising novel agents in combination with personalized medicine will likely continue to improve treatment of these patients.

Ultrasonography in prostate cancer: current roles and potential applications in radiorecurrent disease

The use of ultrasound technology for prostate cancer imaging has evolved over many years. In order to fully appreciate today’s application of prostate ultrasound in the primary diagnostic setting as well as for radiorecurrent prostate cancer, it is helpful to understand the progression of this technology from its inception. This review begins with a brief history of the development of ultrasonography for the prostate. This is followed by a summary of the data evaluating ultrasound in the primary diagnosis of prostate cancer. Its application in the post-treatment setting is then addressed. Finally, several emerging technologies are discussed, including contrast-enhanced ultrasound, elastography and HistoScanning. These new modalities may hold promise for identifying incompletely ablated prostate tissue following radiation therapy or other ablative techniques.