Faculty Bibliography

PURPOSE/OBJECTIVE:Percutaneous biopsy of small renal tumors has not been historically performed because of concern about complications and accuracy. We reviewed our experience with percutaneous needle biopsy of small renal masses to assess the safety and accuracy of the procedure, the potential predictors of a diagnostic result and the role of biopsy in clinical decision making. MATERIALS AND METHODS/METHODS:A total of 100 percutaneous needle biopsies of renal masses less than 4 cm were performed between January 2000 and May 2007 with 18 gauge needles and a coaxial technique under ultrasound and/or computerized tomography guidance. A retrospective chart review was performed to document the complication rate and the ability to obtain sufficient tissue for diagnosis. Tumor size, tumor type (solid vs cystic), image guidance, biopsy number and core length were assessed for the ability to predict a diagnostic biopsy. RESULTS:No tumor seeding or significant bleeding was observed. Of the core biopsies 84 (84%) were diagnostic for a malignant (66) or a benign (18) tumor. Larger tumor size and a solid pattern were significant predictors of a diagnostic result. Histological subtyping and grading were possible on core biopsies in 93% and 68% of renal cell carcinomas, respectively. A total of 20 patients underwent surgery after a diagnostic biopsy. The histological concordance of biopsies and surgical specimens was 100%. CONCLUSIONS:Percutaneous needle biopsy of renal masses less than 4 cm is safe and provides adequate tissue for diagnosis in most cases. Larger tumor size and a solid pattern are significant predictors of a successful biopsy. Renal tumor biopsy decreases the rate of unnecessary surgery for benign tumors and can assist the clinician with treatment decision making, especially in elderly and unfit patients.

PURPOSE/OBJECTIVE:To investigate differences in apparent diffusion coefficient (ADC) and T2 values between dense and sparse regions in prostate cancer. MATERIALS AND METHODS/METHODS:Eighteen patients (median age, 61 years; range, 44-72 years) gave informed consent for this retrospective Research Ethics Board-approved study. Prior to radical prostatectomy, ADC (b value, 600 sec/mm(2)) and T2 maps were obtained by using 1.5-T magnetic resonance (MR) imaging. Twenty-eight peripheral zone (PZ) tumors were reviewed by using whole-mount histologic findings, and regions assessed to contain primarily (>60%) normal PZ tissue were delineated. Tumors were categorized as "sparse" if more than 50% of their cross-sectional areas were these primarily normal PZ regions and were considered "dense" otherwise. Normal PZ tissue was outlined separately on the same section. Tumor and normal tissue outlines were transferred to corresponding ADC and T2 maps, and median values were calculated. Values were compared by using multiple regression analysis. Matched-pair tumor-to-normal tissue differences and log(2)-transformed ratios were assessed by using nonparametric tests. RESULTS:Thirty-six percent (10 of 28) of tumors were sparse; 64% (18 of 28) were dense. For both overall and intrapatient comparisons, dense tumors had significantly lower ADC and T2 values than normal PZ tissue (P < .05), but no significant differences were observed between sparse tumors and normal tissue. Log(2)-transformed tumor-to-normal tissue ratios were significantly less than zero for dense tumors for both ADC and T2 (P < .01) measurements but not for sparse tumors. Both matched-pair differences and log(2)-transformed ratios were significantly different between sparse and dense tumors (P < .01). ADC and T2 values were moderately correlated (Pearson correlation coefficient range, r = 0.770-0.804). CONCLUSION/CONCLUSIONS:Sparse prostate tumors have similar ADC and T2 values to those of normal PZ tissue. This may limit MR imaging detection and the assessment of tumor volume of some cancers.

Breast needle core biopsy (NCB) is now a standard diagnostic procedure in the triple assessment of screen detected breast lesions. Therefore, it is important to provide robust and up-to-date data on the performance of NCB in the screening setting. However, previous studies of NCB have suffered from either limitation in the number of assessed cases or included a mix of symptomatic and screen detected breast lesions. In this study, we have evaluated the performance of a large series of uniformly assessed NCBs of screen detected lesions (20001 cases) over a period of 10 years (1997-2007). Our results showed a gradual increase in the number of NCBs and an improvement of their performance over the period of the study; absolute sensitivity increased from 84.9% to 96.4% and complete sensitivity increased from 90.9% to 99.7%. There was also a gradual reduction in the number of surgical interventions after benign (B2) and negative (B1) NCB diagnoses. Our study provides data showing variance from the suggested thresholds for the measures of performance of NCB in the United Kingdom which could be used to provide updated evidence-based thresholds for assessment of performance of NCB diagnosis use in the assessment of breast cancer screen detected lesions in the UK and elsewhere.

Accurate Gleason score, pathologic stage, and surgical margin (SM) information is critical for the planning of post-radical prostatectomy management in patients with prostate cancer. Although interobserver variability for Gleason score among urologic pathologists has been well documented, such data for pathologic stage and SM assessment are limited. We report the first study to address interobserver variability in a group of expert pathologists concerning extraprostatic soft tissue (EPE) and SM interpretation for radical prostatectomy specimens. A panel of 3 urologic pathologists selected 6 groups of 10 slides designated as being positive, negative, or equivocal for either EPE or SM based on unanimous agreement. Twelve expert urologic pathologists, who were blinded to the panel diagnoses, reviewed 40x whole-slide scans and provided diagnoses for EPE and SM on each slide. On the basis of panel diagnoses, as the gold standard, specificity, sensitivity, and accuracy values were high for both EPE (87.5%, 95.0%, and 91.2%) and SM (97.5%, 83.3%, and 90.4%). Overall kappa values for all 60 slides were 0.74 for SM and 0.63 for EPE. The kappa values were higher for slides with definitive gold standard EPE (kappa=0.81) and SM (kappa=0.73) diagnoses when compared with the EPE (kappa=0.29) and SM (kappa=0.62) equivocal slides. This difference was markedly pronounced for EPE. Urologic pathologists show good to excellent agreement when evaluating EPE and SM. Interobserver variability for EPE and SM interpretation was principally related to the lack of a clearly definable prostatic capsule and crush/thermal artifact along the edge of the gland, respectively.

OBJECTIVE:Basal phenotype has been found to be an independent poor prognostic factor for breast cancer. The aim of this study was to assess the mammographic appearance of screening-detected breast carcinoma with the basal phenotype. MATERIALS AND METHODS/METHODS:A series of 1,944 consecutively enrolled patients with operable invasive breast cancer underwent immunohistochemical analysis with cytokeratin 5/6 and cytokeratin 14 markers to identify tumors exhibiting basal phenotype characteristics. Among those patients, 356 women with breast cancer were common to a prospectively collected database of screening-detected cases of breast cancer. The predominant mammographic appearance and any associated features were reported by experienced image readers blinded to phenotype status. A chi-square test was used to assess difference between the mammographic appearances of a group of tumors with the basal phenotype and those of a group with the nonbasal phenotype. RESULTS:Forty-one (12%) of the screening-detected tumors had basal phenotypic expression, and these were compared with 309 (88%) nonbasal tumors. Basal-phenotype tumors were significantly more likely to manifest as an ill-defined mass (basal phenotype, 25 [61%] of 41 tumors; nonbasal phenotype, 75 [24%] of 309 tumors; p < 0.001) or with comedo calcification (basal phenotype, nine [22%] of 41 tumors; nonbasal phenotype, 30 [10%] of 309 tumors; p = 0.019). Nonbasal-phenotype tumors were more likely to manifest as a spiculated mass (nonbasal phenotype, 150 [49%] of 309 tumors; basal phenotype, eight [20%] of 41 tumors; p < 0.001). The low rate of spiculation in basal tumors was independent of histologic grade. CONCLUSION/CONCLUSIONS:Screening-detected breast tumors with a basal phenotype have a mammographic appearance different from that of nonbasal tumors. This finding may explain the good prognostic value of mammographic spiculation reported in previous studies.

The loss of functional von Hippel-Lindau (VHL) tumor suppressor gene is associated with the development of clear-cell renal cell carcinoma (CC-RCC). Recently, VHL was shown to promote the transcription of E-cadherin, an adhesion molecule whose expression is inversely correlated with the aggressive phenotype of numerous epithelial cancers. Here, we performed immunohistochemistry on CC-RCC tissue microarrays to determine the prognostic value of E-cadherin and VHL with respect to Fuhrman grade and clinical prognosis. Low Fuhrman grade and good prognosis associated with positive VHL and E-cadherin immunoreactivity, whereas poor prognosis and high-grade tumors associated with a lack of E-cadherin and lower frequency of VHL staining. A significant portion of CC-RCC with positive VHL immunostaining correlated with nuclear localization of C-terminally cleaved E-cadherin. DNA sequencing revealed in a majority of nuclear E-cadherin-positive CC-RCC, subtle point mutations, deletions and insertions in VHL. Furthermore, nuclear E-cadherin was not observed in chromophobe or papillary RCC, as well as matched normal kidney tissue. In addition, nuclear E-cadherin localization was recapitulated in CC-RCC xenografts devoid of functional VHL or reconstituted with synthetic mutant VHL grown in SCID mice. These findings provide the first evidence of aberrant nuclear localization of E-cadherin in CC-RCC harboring VHL mutations, and suggest potential prognostic value of VHL and E-cadherin in CC-RCC.

The most prevalent mutations associated with the development of clear-cell renal cell carcinoma (CC-RCC) are the loss-of-function mutations of von Hippel-Lindau (VHL) tumor suppressor gene. These mutations invariably result in an inappropriate accumulation of HIF-alpha due to a failure of VHL as a substrate-recognition component of an E3 ubiquitin ligase complex to target HIFalpha for oxygen-dependent ubiquitin-mediated destruction. Stabilization of HIF-2alpha, but not HIF-1alpha, is the critical oncogenic event upon the functional loss of VHL in the development of CC-RCC. Here, we show that HIF-3alpha4, an alternatively spliced variant of human HIF-3alpha with similar domain structure as the murine inhibitory PAS protein (IPAS), forms an abortive transcriptional complex with HIF-2alpha and prevents the engagement of HIF-2 to the hypoxia-responsive elements (HREs) located in the promoter/ enhancer regions of hypoxia-inducible genes. In addition, the re-expression of HIF-3alpha4 in VHL-null 786-O CC-RCC cells via adenovirus decreases the endogenous expression of HIF-2-driven gene expression and suppresses the growth of 786-O tumor xenografts in SCID mice. These results suggest that HIF-3alpha4 is a naturally occurring dominant-negative HIF-3alpha splice isoform with tumor suppressive activity and support the targeted delivery of HIF-3alpha4 as a potential therapeutic option to curtail HIF-dependent tumor progression.

PURPOSE/OBJECTIVE:The incidence of renal cell carcinoma is increasing worldwide and there are new treatments for localized as well as metastatic tumors. The traditional role for percutaneous biopsy of renal masses has been limited, and so there is little general experience. There have been concerns about safety and accuracy. This review provides an update on the current techniques, indications and accuracy of needle biopsy of renal tumors. MATERIALS AND METHODS/METHODS:PubMed and MEDLINE were searched for English language reports of percutaneous needle core biopsy and fine needle aspiration of renal tumors that were published from 1977 to 2006. RESULTS:With the development of new biopsy techniques and wider experience with percutaneous probe ablation therapies the risk of tumor seeding appears negligible. Significant bleeding is unusual and almost always self-limiting. At centers with expertise needle core biopsy with or without fine needle aspiration appears to provide adequate specimens for an accurate diagnosis in more than 90% of renal masses. CONCLUSIONS:Percutaneous biopsy of renal masses appears to be safe and it carries minimal risk of tumor spread. Urologists should consider increasing the indications for renal biopsy of small renal masses that appear to be renal cell carcinoma, especially in elderly and unfit patients. With more experience and followup preoperative biopsy has the potential to decrease unnecessary treatment since up to a third of small renal masses are now reported to be benign at surgery. Percutaneous biopsy may also allow a better selection of renal tumors for active surveillance and minimally invasive ablative therapies. Finally, there is potential for stratifying initial therapy for metastatic renal cell carcinoma by histological subtype and in the future molecular characteristics.

OBJECTIVE:The objective of our study was to compare T2-weighted MRI alone and T2 combined with diffusion-weighted imaging (DWI) for the localization of prostate cancer. SUBJECTS AND METHODS/METHODS:T2-weighted imaging and DWI (b value = 600 s/mm2) were performed in 49 patients before radical prostatectomy using an endorectal coil at 1.5 T in this prospective trial. The peripheral zone of the prostate was divided into sextants and the transition zone into left and right halves. T2 images alone and then T2 images combined with apparent diffusion coefficient (ADC) maps (T2 + DWI) were scored for the likelihood of tumor and were compared with whole-mount histology results. Fixed window and level settings were used to display the ADC maps. Only tumors with an area of more than 0.13 cm2 (> 4 mm diameter) and a Gleason score of > or = 6 were considered significant. The area under the receiver operating characteristic curve (A(z)) was used to assess accuracy. RESULTS:In the peripheral zone, the A(z) value was significantly higher (p = 0.004) for T2 plus DWI (A(z) = 0.89) than for T2 imaging alone (A(z) = 0.81). Performance was poorer in the transition zone for both T2 plus DWI (A(z) = 0.78) and T2 (A(z) = 0.79). For the whole prostate, sensitivity was significantly higher (p < 0.001) with T2 plus DWI (81% [120/149]) than with T2 imaging alone (54% [81/149]), with T2 plus DWI showing only a slight loss in specificity compared with T2 imaging alone (84% [204/243] vs 91% [222/243], respectively). CONCLUSION/CONCLUSIONS:Combined T2 and DWI MRI is better than T2 imaging alone in the detection of significant cancer (Gleason score > or = 6 and diameter > 4 mm) within the peripheral zone of the prostate.

PURPOSE/OBJECTIVE:To prospectively evaluate the magnetic resonance (MR) imaging appearance of the prostate and periprostatic tissues after vascular targeted photodynamic therapy (VTP) with palladium-bacteriopheophorbide for locally recurrent carcinoma after external beam radiation therapy. MATERIALS AND METHODS/METHODS:Informed consent was obtained from all patients, and approval was obtained from the ethics review boards of all participating institutions. Nonenhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MR imaging examinations were performed at baseline and 1 week, 4 weeks, and 6 months after VTP in 25 men (age range, 58-83 years; mean age, 73 years) as part of a prospective phase I/II trial. Percentage of MR-depicted necrosis was defined as the volume of nonenhancing prostatic tissue 1 week after VTP divided by the volume of the prostate. Patterns of intra- and extraprostatic necrosis were recorded. Pearson correlation coefficients were used to test correlations between necrosis and prostate-specific antigen level. RESULTS:Contrast material-enhanced T1-weighted MR images obtained 1 week after therapy showed necrosis in all patients. Treatment margins were irregular in 21 of 25 patients. T2-weighted images showed no clear treatment boundaries in any patient. Extraprostatic necrosis involved the puborectalis or levator ani muscles in 22, obturator internus muscle in 12, periprostatic veins in three, pubic bone marrow in four, and anterior rectal wall in nine of the 25 patients. The neurovascular bundle appeared to be spared in all patients. Percentage of MR-depicted intraprostatic necrosis was correlated with percentage decrease in prostate-specific antigen level (from baseline) at 4 weeks (r=0.41, P=.04) and 12 weeks (r=0.45, P=.02). CONCLUSION/CONCLUSIONS:Contrast-enhanced MR imaging depicts irregular margins of intraprostatic treatment effect. This finding suggests varied tissue sensitivities to VTP with palladium-bacteriopheophorbide.