Edward N. Rampersaud

Radiation Exposure in the Acute and Short-Term Management of Urolithiasis at 2 Academic Centers

PURPOSE Diagnostic imaging has a central role in the evaluation and management of urolithiasis. A variety of modalities are available, each with benefits and limitations. Without careful consideration of imaging modalities in quantity and type patients may receive excessive doses of radiation during initial diagnostic and followup evaluations. Therefore, we determined the effective radiation dose associated with an acute stone episode and short-term followup. MATERIALS AND METHODS A multicenter retrospective study of all patients who presented with an acute stone episode was performed. The analysis included all imaging studies related to stone disease performed within 1 year of the acute event. Using accepted effective radiation dose standards for each of these examinations, the total radiation dose administered was calculated and compared by patient characteristics including stone location, stone number and intervention strategy. The primary outcome assessed was a total radiation dose greater than 50 mSv, the recommended yearly dose limit for occupational exposure by the International Commission on Radiological Protection. RESULTS We identified 108 patients who presented to our respective institutions with a primary acute stone episode between 2000 and 2006. The mean age in our cohort was 48.6 years and 50% of the patients were men. Patients underwent an average of 4 radiographic examinations during the 1-year period. Studies performed included a mean of 1.2 plain abdominal films of the kidneys, ureters and bladder (range 0 to 7), 1.7 abdominopelvic computerized tomograms (range 0 to 6) and 1 excretory urogram (range 0 to 3) during the first year of followup. The median total effective radiation dose per patient was 29.7 mSv (IQR 24.2, 45.1). There were 22 (20%) patients who received greater than 50 mSv. Analysis of stone location, number of stones, stone composition, patient age, sex and surgical intervention indicated no statistically significant difference in the probability of receiving a total radiation dose greater than 50 mSv. CONCLUSIONS A fifth of patients receive potentially significant radiation doses in the short-term followup of an acute stone event. Radiographic imaging remains an integral part of the diagnosis and management of symptomatic urolithiasis. While debate exists regarding the threshold level for radiation induced fatal malignancies, urologists must be cognizant of the radiation exposure to patients, and seek alternative imaging strategies to minimize radiation dose during acute and long-term stone management.

Targeted β-Adrenergic Receptor Kinase (βARK1) Inhibition by Gene Transfer in Failing Human Hearts

Background—Failing human myocardium is characterized by an attenuated contractile response to &bgr;-adrenergic receptor (&bgr;AR) stimulation due to changes in this signaling cascade, including increased expression and activity of the &bgr;-adrenergic receptor kinase (&bgr;ARK1). This leads to desensitization and downregulation of &bgr;ARs. Previously, expression of a peptide inhibitor of &bgr;ARK1 (&bgr;ARKct) has proven beneficial in several animal models of heart failure (HF). Methods and Results—To test the hypothesis that inhibition of &bgr;ARK1 could improve &bgr;-adrenergic signaling and contractile function in failing human myocytes, the &bgr;ARKct was expressed via adenovirus-mediated (Ad&bgr;ARKct) gene transfer in ventricular myocytes isolated from hearts explanted from 10 patients with end-stage HF undergoing cardiac transplantation. Ad&bgr;ARKct also contained the marker gene, green fluorescent protein, and successful gene transfer was confirmed via fluorescence and immunoblotting. Compared with uninfected failing myocytes (control), the velocities of both contraction and relaxation in the Ad&bgr;ARKct-treated cells were increased in response to the &bgr;-agonist isoproterenol (contraction: 57.5±6.6% versus 37.0±4.2% shortening per second, P <0.05; relaxation: 43.8±5.5% versus 27.5±3.9% lengthening per second, P <0.05). Fractional shortening was similarly enhanced (12.2±1.2% versus 8.0±0.9%, P <0.05). Finally, adenylyl cyclase activity in response to isoproterenol was also increased in Ad&bgr;ARKct-treated myocytes. Conclusions—These results demonstrate that as in animal models of HF, expression of the &bgr;ARKct can improve contractile function and &bgr;-adrenergic responsiveness in failing human myocytes. Thus, &bgr;ARK1 inhibition may represent a therapeutic strategy for human HF.

Small renal mass biopsy--how, what and when: report from an international consensus panel.

To discuss the use of renal mass biopsy (RMB) for small renal masses (SRMs), formulate technical aspects, outline potential pitfalls and provide recommendations for the practicing clinician. The meeting was conducted as an informal consensus process and no scoring system was used to measure the levels of agreement on the different topics. A moderated general discussion was used as the basis for consensus and arising issues were resolved at this point. A consensus was established and lack of agreement to topics or specific items was noted at this point. Recommended biopsy technique: at least two cores, sampling different tumour regions with ultrasonography being the preferred method of image guidance. Pathological interpretation: ‘non‐diagnostic samples’ should refer to insufficient material, inconclusive and normal renal parenchyma. For non‐diagnostic samples, a repeat biopsy is recommended. Fine‐needle aspiration may provide additional information but cannot substitute for core biopsy. Indications for RMB: biopsy is recommended in most cases except in patients with imaging or clinical characteristics indicative of pathology (syndromes, imaging characteristics) and cases whereby conservative management is not contemplated. RMB is recommended for active surveillance but not for watchful‐waiting candidates. We report the results of an international consensus meeting on the use of RMB for SRMs, defining the technique, pathological interpretation and indications.

Percent Tumor Involvement and Risk of Biochemical Progression After Radical Prostatectomy

PURPOSE Percent tumor involvement has been associated with biochemical progression in organ confined disease, although its role in predicting outcome in men with more advanced disease pathology is unclear. We hypothesized percent tumor involvement may be a good correlate of outcome in all stages of prostate cancer. MATERIALS AND METHODS We examined the association between percent tumor involvement in the radical prostatectomy specimen and the outcome measures of pathological stage and biochemical progression using multivariate logistic regression and Cox proportional hazards analysis, respectively, in 2,220 patients from the Duke Prostate Center radical prostatectomy database. RESULTS On multivariate analysis, percent tumor involvement significantly predicted the risk of positive margins (p <0.001), extracapsular extension (p <0.001), seminal vesicle invasion (p <0.001) and biochemical progression (HR 1.16, 95% CI 1.01-1.33, p = 0.035). The percent tumor involvement cut points of 5% or less, 6% to 20%, 21% to 50% and greater than 50% significantly separated men in groups with differing biochemical progression risk (p <0.001). In addition, these cut points were further able to stratify men among those with organ confined margin negative disease (p <0.001), either positive margins or extracapsular extension (p <0.001), and those with seminal vesicle invasion (p = 0.02). CONCLUSIONS Percent tumor involvement was a significant predictor of biochemical progression and was able to further stratify men who were already assigned to narrowly defined pathological groups. If confirmed in other studies, percent tumor involvement may enable the clinician to identify the high risk patient who stands to benefit the most from adjuvant therapy.

Prostate-specific antigen (PSA) and PSA velocity for prostate cancer detection in men aged < 50 years

Many of the papers in this section are specifically related to the complexities of PSA testing and prostatic biopsy. Increasingly PSA testing has become a constituent part of urological practice, and although most would maintain that its is the best urological marker for prostate cancer that we have, its failings have led us to examine its performance in microscopic detail, to help us to use it better for detecting prostatic cancer.

Gain of Chromosome 8q Is Associated With Metastases and Poor Survival of Patients With Clear Cell Renal Cell Carcinoma

The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease‐specific survival (DSS).

Clinical, Molecular, and Genetic Correlates of Lymphatic Spread in Clear Cell Renal Cell Carcinoma

BACKGROUND While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood. OBJECTIVE Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas. DESIGN, SETTING, AND PARTICIPANTS A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively. MEASUREMENTS Fisher exact test or the χ(2) test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread. RESULTS AND LIMITATIONS In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience. CONCLUSIONS The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.

Smoking Negatively Impacts Renal Cell Carcinoma Overall and Cancer-Specific Survival

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC.

Prognostic value of microvascular invasion in predicting the cancer specific survival and risk of metastatic disease in renal cell carcinoma: a multicenter investigation

PURPOSE While microvascular invasion is an accepted risk factor in various cancers, its prognostic role in renal cell carcinoma is still unclear. Therefore, a large multicenter study examining the experience of 5 international institutions was performed to evaluate the prognostic value of microvascular invasion in the occurrence of metastases and cancer specific survival. MATERIALS AND METHODS A total of 2,596 patients (475 with microvascular invasion and 2,121 without microvascular invasion) having up to 212 (median 22.4) months of followup were compared for differences in clinicopathological features, occurrence of metastases and cancer specific survival. RESULTS Patients with microvascular invasion presented with higher age (p = 0.001) and a worse Eastern Cooperative Oncology Group performance status (p <0.0001). Microvascular invasion was associated with larger tumor diameter (p <0.0001), higher Fuhrman grade (p <0.0001), more advanced pT stage (p <0.0001), and the presence of lymph node and distant metastases (p <0.0001). In particular, in nonmetastatic cases worse survival was associated with microvascular invasion (p <0.0001, HR 2.38). Univariate analysis demonstrated a strong correlation between microvascular invasion and cancer specific survival (p <0.0001). However, after controlling for gender, Eastern Cooperative Oncology Group performance status, Fuhrman grade and TNM stage statistical significance was lost. Of interest, low stage tumors with microvascular invasion were strongly correlated with the occurrence of metastases (p <0.0001). CONCLUSIONS Microvascular invasion occurs in nearly 1 of 5 patients with renal cell carcinoma, is tightly correlated with adverse clinicopathological features and is an independent predictor of metastatic spread including in those presenting with low stage tumors.

A man with saphenous vein graft aneurysms after bypass surgery.

Saphenous vein graft (SVG) aneurysms are a rare complication of coronary artery bypass graft surgery. Patients in whom these aneurysms form a fistula with either a cardiac chamber or mediastinal vessel are even more uncommon and present a difficult diagnostic and therapeutic challenge. We present a patient with SVG aneurysms and a fistula to the left atrium.