Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer.

PURPOSE: Prostate specific antigen has limited performance in detecting prostate cancer. The transcription factor GATA2 is expressed in aggressive prostate cancer. We analyzed the predictive value of urine extracellular vesicle GATA2 mRNA alone and in combination with a multigene panel to improve detection of prostate cancer and high risk disease. MATERIALS AND METHODS: GATA2 mRNA was analyzed in matched extracellular vesicles isolated from urines before and after prostatectomy (16) and paired urine and tissue prostatectomy samples (19). Extracellular vesicle GATA2 mRNA performance to distinguish prostate cancer and high grade disease was tested in training (52) and validation (165) cohorts. The predictive value of a multigene score including GATA2, PCA3 and TMPRSS2-ERG (GAPT-E) was tested in both cohorts. RESULTS: Confirming its prostate origin, urine extracellular vesicle GATA2 mRNA levels decreased significantly after prostatectomy and correlated with prostate cancer tissue GATA2 mRNA levels. In the training and validation cohort GATA2 discriminated prostate cancer (AUC 0.74 and 0.66) and high grade disease (AUC 0.78 and 0.65), respectively. Notably, the GAPT-E score improved discrimination of prostate cancer (AUC 0.84 and 0.72) and high grade cancer (AUC 0.85 and 0.71) in both cohorts when compared with each biomarker alone and PT-E (PCA3 and TMPRSS2-ERG). A GAPT-E score for high grade prostate cancer would avoid 92.1% of unnecessary prostate biopsies, compared to 61.9% when a PT-E score is used. CONCLUSIONS: Urine extracellular vesicle GATA2 mRNA analysis improves the detection of high risk prostate cancer and may reduce the number of unnecessary biopsies.

Costs of early adjuvant radiation therapy after radical prostatectomy: a decision analysis.

BACKGROUND: This analysis was carried out to evaluate the cost-effectiveness of adjuvant radiation therapy (ART) versus observation, using a decision analysis model based primarily upon the published results of the Southwest Oncology Group prospective trial (SWOG 8794). PATIENTS AND METHODS: A decision analysis model was designed to compare ART versus observation over a 10-year time horizon. Probabilities of treatment success, utilization of salvage treatments, and rates of adverse events were taken from published results of SWOG 8794. Cost inputs were based on 2010 Medicare reimbursement rates. Primary outcome measure was incremental cost per prostate-specific antigen (PSA) success (i.e. serum PSA level <0.4 ng/ml). RESULTS: ART results in a higher PSA success rate than observation with probability of 0.43 versus 0.22. The mean incremental cost per patient for ART versus observation was $6023. The mean incremental cost-effectiveness ratio was $26,983 over the 10-year period. CONCLUSIONS: ART appears cost effective compared with observation based upon this decision analysis model. Future research should consider more costly radiation therapy (RT) approaches, such as intensity-modulated RT, and should evaluate the cost-effectiveness of ART versus early salvage RT.

Molecular genetics of prostate cancer: clinical translational opportunities.

Prostate cancer (PC) development reflects a complex sequence of biologic and molecular events. Several inheritable and somatic genetic changes have been identified. The knowledge of the molecular basis of PC can improve our understanding of the causes of this common cancer and provide information on prognosis and treatment. To date, however, no molecular studies have yet yielded consistent information that is ready to be incorporated into clinical practice. We reviewed the current literature on the molecular biology of prostate cancer and analyzed different potential tumor markers according to the classical concepts of oncogenes, suppressor genes, and the more modern concepts of genes involved in detoxification or inflammatory pathways of cancer progression. This review aims to identify trends in PC research and suggests potential clinical applications for diagnosis, prognosis, prevention and treatment.

Molecular genetics of bladder cancer: targets for diagnosis and therapy.

Transitional cell carcinoma of the bladder is a common tumor. While most patients presenting superficial disease can be expected to do well following treatment, still many patients will return to our office with muscle invasive and metastatic disease. Survival in advanced bladder cancer is less than 50%. Tumors of similar histologic grade and stage have variable behavior, suggesting that genetic alterations must be present to explain the diverse behavior of bladder cancer. It is hoped that through the study of the subtle genetic alterations in bladder cancer, important prognostic and therapeutic targets can be exploited. Many new diagnostic tests and gene therapy approaches rely on the identification and targeting of these unique genetic alterations. A review of literature published on the molecular genetics of bladder cancer from 1970 to the present was conducted. A variety of molecular genetic alterations have been identified in bladder cancer. Oncogenes (H-ras, erbB-2, EGFR, MDM2, C-MYC, CCND1), tumor suppressor genes (p53, Rb, p21, p27/KIP1, p16, PTEN, STK15, FHIT, FEZ1/LZTS1, bc10), telomerase, and methylation have all been studied in bladder cancer. Several have proven to be potentially useful clinical targets in the prognosis and therapy of bladder cancer such as staining for p53 and gene therapy strategies such as p53 and fez1. Clinical trials targeting HER2/neu and the EGFR pathways are underway. The UroVysion bladder cancer assay relies on FISH to detect genetic alterations in this disease. Continuing identification of the molecular genetic alterations in bladder cancer will enhance future diagnostic and therapeutic approaches to bladder cancer. Capitalizing on these alterations will allow early detection, providing important prognostic information and unique targets for gene therapy and other therapeutic approaches.

Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells.

Intravesical administration of Bacillus Calmette-Guérin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG-specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA-dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.

Expression of transforming growth factor alpha in normal human adult kidney and enhanced expression of transforming growth factors alpha and beta 1 in renal cell carcinoma.

Normal kidney and renal cell carcinoma tissues from ten patients were studied for mRNA and DNA for both transforming growth factors alpha and beta 1. Northern and Southern hybridizations were conducted on samples extracted from the solid tumor and surrounding normal tissues and two tumor-derived cell lines. Low levels of constitutive expression of TGF-alpha mRNA were detected in all normal kidney tissues; six of the ten patients, however, demonstrated an increased (2- to 8-fold) expression of TGF-alpha in the tumor versus normal kidney as determined by densitometry of RNA blots. All ten patients had elevated mRNA levels for TGF-beta 1 in the tumor (2.5-to 22-fold increase) relative to normal kidney. Two tumor-derived cell lines also expressed TGF-alpha and TGF-beta 1 mRNA. Southern blot hybridization of the DNA extracted from the normal tumor pairs revealed no gene amplification or gross rearrangement for either the TGF-alpha or TGF-beta 1 genes. These results demonstrate the expected constitutive expression of TGF-beta 1 by normal kidney; however, the constitutive expression of TGF-alpha by Northern blot analysis in normal adult human kidney is previously unreported. Enhanced expression of TGF-alpha and TGF-beta 1 mRNA in solid tumor may be related to the development of renal cell carcinoma.

Detection of hematogenous micrometastasis in patients with prostate cancer.

The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk.

BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis. Adjuvant radiation treatment (ART, n=111), minimal residual disease (MRD) SRT (n=70) and SRT (n=83) were defined by PSA levels of <0.2, 0.2-0.49 and ⩾0.5 ng ml(-1), respectively, before radiation therapy (RT) initiation. Remaining 157 men who did not receive additional therapy before metastasis formed the no RT arm. Clinical-genomic risk was assessed by Cancer of the Prostate Risk Assessment Post-Surgical (CAPRA-S) and Decipher. Cox regression was used to evaluate the impact of treatment on outcome. RESULTS: During the study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on multivariable analysis for metastasis (P<0.05). Adjusting for clinical-genomic risk, SRT and no RT had hazard ratios of 4.31 (95% confidence interval, 1.20-15.47) and 5.42 (95% confidence interval, 1.59-18.44) for metastasis compared with ART, respectively. No significant difference was observed between MRD-SRT and ART (P=0.28). Men with low-to-intermediate CAPRA-S and low Decipher value have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. CONCLUSIONS: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and patients to balance risks of morbidity with improved oncological outcomes. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.

Decipher correlation patterns post prostatectomy: initial experience from 2 342 prospective patients.

BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed. For clinical testing, tumor specimen from the highest Gleason grade was sampled using a 1.5 mm tissue punch. Decipher scores were calculated based on a previously locked model. Correlations between Decipher score and clinicopathologic variables were computed using Spearman's rank correlation. Mixed-effect linear models were used to study the association of practice type and Decipher score. The significance level was 0.05 for all tests. RESULTS: Decipher score had a positive correlation with pathologic Gleason score (PGS; r=0.37, 95% confidence interval (CI) 0.34-0.41), pathologic T-stage (r=0.31, 95% CI 0.28-0.35), CAPRA-S (r=0.32, 95% CI 0.28-0.37) and patient age (r=0.09, 95% CI 0.05-0.13). Decipher reclassified 52%, 76% and 40% of patients in CAPRA-S low-, intermediate- and high-risk groups, respectively. We detected a 28% incidence of high-risk disease through the Decipher score in pT2 patients and 7% low risk in pT3b/pT4, PGS 8-10 patients. There was no significant difference in the Decipher score between patients from community centers and those from academic centers (P=0.82). CONCLUSIONS: Although Decipher correlated with baseline tumor characteristics for over 2 000 patients, there was significant reclassification of tumor aggressiveness as compared to clinical parameters alone. Utilization of the Decipher genomic classifier can have major implications in assessment of postoperative risk that may impact physician-patient decision making and ultimately patient management.

Immunologic approaches to the treatment of prostate cancer.

The presence of several organ-specific molecules that could serve as immunogens or targets of an immune attack, the nonessential nature of the prostate gland, the substantial failure rate after treatment of the primary tumor, and the lack of effective chemotherapy for metastatic disease make prostate cancer an ideal candidate for immunotherapy. This report reviews the current status of two novel approaches to the treatment of prostate cancer. The first is an effort to induce antitumor immunity by enriching the cytokine environment within the primary cancer by intraprostatic injection of Leukocyte Interleukin (Cel-Sci Corp, Vienna, VA), a mixture of natural cytokines that includes interleukin-1 beta (IL-1beta), IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). The second approach uses OncoVax-P (Jenner Biotherapies, Inc, San Ramon, CA), a vaccine consisting of liposome-encapsulated recombinant prostate-specific antigen (PSA) and lipid A. When administered as an emulsion or in association with bacillus Calmette-Guérin (BCG)/cyclophosphamide or GM-CSF with or without IL-2/cyclophosphamide, immunologic tolerance is broken as evidenced by the generation of humoral and cellular immunity. Both of these approaches have been shown to be feasible and safe, and are now being tested in patients with less advanced disease to determine if manipulation of the immune system can favorably influence clinical outcome.

The efficacy of early adjuvant radiation therapy for pT3N0 prostate cancer: a matched-pair analysis.

PURPOSE: This study examines the effect of adjuvant radiation therapy (RT) on outcome in patients with pT3N0 prostate cancer and makes comparisons to a matched control group. METHODS AND MATERIALS: At our center, 149 patients undergoing radical prostatectomy were found to have pT3N0 prostate cancer, had an undetectable postoperative prostate-specific antigen (PSA) level, and had no immediate hormonal therapy. Fifty-two patients received adjuvant RT within 3 to 6 months of surgery. Ninety-seven underwent radical prostatectomy alone and were observed until PSA failure. From these two cohorts, we matched patients 1:1 according to preoperative PSA (<10 ng/ml vs. >10 ng/ml), Gleason score (<7 vs. > or =7), seminal vesicle invasion, and surgical margin status. Seventy-two patients (36 pairs) were included in the analysis. Median follow-up time was 41 months. We calculated a matched-pairs risk ratio for cumulative risk of PSA relapse (a rise above 0.2 ng/ml). RESULTS: After controlling for the prognostic factors by matching, there was an 88% reduction (95% confidence interval [CI]: 78-93%) in the risk of PSA relapse associated with adjuvant RT. The 5-year freedom from PSA relapse rate was 89% (95% CI: 76-100%) for patients receiving adjuvant RT as compared to 55% (95% CI: 34-79%) for those undergoing radical prostatectomy alone. CONCLUSIONS: These data suggest that adjuvant RT for pT3N0 prostate cancer may significantly reduce the risk of PSA failure as compared to radical prostatectomy alone. Its effect on clinical outcome awaits further follow-up.

Effect of higher radiation dose on biochemical control after radical prostatectomy for PT3N0 prostate cancer.

PURPOSE: The appropriate radiation dose has not been determined for postoperative radiation therapy (RT) of prostate cancer. Postoperative PSA level is a useful marker of local residual disease, and may allow evaluation of RT dose-response after radical prostatectomy. METHODS AND MATERIALS: Between 1989 and 1996, 86 consecutive patients with pT3N0 prostate cancer who did not receive prior hormonal therapy or chemotherapy were irradiated postoperatively. All patients received 55.8 to 70.2 Gy (median = 64.8 Gy) to the prostatic/seminal vesicle bed. Patients were judged to be free of biochemical failure (bNED) if their PSA remained undetectable or decreased to undetectable level (< 0.2 ng/ml). The median follow-up time was 32 months from time of irradiation. RESULTS: Univariate and multivariate analyses of variables showed that the preRT PSA level was the most significant predictor of improved bNED survival (p < 0.001). Actuarial analyses of radiation dose grouped with preRT PSA levels found higher radiation dose to be significant (p < 0.05). For the 52 patients with an undetectable preRT PSA level, the 3-year bNED rate was 91% for patients irradiated to 61.5 Gy or more and 57% for those irradiated to lower doses (p = 0.01). For the 21 patients with preRT PSA level > 0.2 and < or = 2.0 ng/ml, the 3-year bNED rate was 79% for patients irradiated to 64.8 Gy or more and 33% for those irradiated to a lower dose (p = 0.02). No other preRT PSA interval or radiation dose level was associated with a dose-response function. CONCLUSION: In patients with pT3N0 prostate cancer after radical prostatectomy, a radiation dose-response function may be present and depends on the preRT PSA value. Patients with high postoperative PSA levels (> 2.0 ng/ml) may be less likely to benefit from higher doses of RT, and should be considered a group for which systemic therapy should be tested.

Does hormonal therapy influence sexual function in men receiving 3D conformal radiation therapy for prostate cancer?

PURPOSE: We evaluated the effect of three-dimensional conformal radiation therapy (3D-CRT) with or without hormonal therapy (HT) on sexual function (SF) in prostate cancer patients whose SF was known before all treatment. METHODS AND MATERIALS: Between March 1996 and March 1999, 144 patients received 3D-CRT (median dose = 70.2 Gy, range 66.6-79.2 Gy) for prostate cancer and had pre- and post-therapy SF data. All SF data were obtained with the O'Leary Brief SF Inventory, a self-administered, multidimensional, validated instrument. We defined total sexual potency as erections firm enough for penetration during intercourse. Mean follow-up time was 21 months (SD +/- 11 months). The Wilcoxon signed-rank test was used to test for significance of the change from baseline. RESULTS: Before 3D-CRT, 87 (60%) of 144 men were totally potent as compared to only 47 (47%) of 101 at 1-year follow-up. Of the 60 men totally potent at baseline and followed for at least 1 year, 35 (58%) remained totally potent. These changes corresponded to a significant reduction in SF (p < 0.05). Patients who had 3D-CRT alone were more likely to be totally potent at 1 year than those receiving 3D-CRT with HT (56% vs. 31%, p = 0.012); however, they were also more likely to be potent at baseline (71% vs. 44%, p = 0.001). Although these two groups had a significant reduction in SF from baseline, their change was not significantly different from each other. CONCLUSION: These data indicate that 3D-CRT causes a significant reduction in total sexual potency as compared to pretreatment baseline. The addition of HT does not appear to increase the risk of sexual dysfunction.

The surgical implications of herniation of the urinary bladder.

The urinary bladder is often involved in an inguinal hernia, but herniation of the entire bladder into the scrotum is rare. As many as 4% of inguinal hernias may involve the bladder, usually in the form of a sliding hernia. Most urinary bladder herniations are diagnosed at the time of inguinal herniorrhaphy, and are therefore most commonly repaired through an inguinal incision. If the diagnosis requires amendment, alternative surgical approaches are available. We studied two patients with massive inguinoscrotal herniation of the urinary bladder, commonly referred to as "scrotal cystocele." We reviewed the literature, incidence, causes, diagnosis, and surgical consideration of herniation of the urinary bladder, and gave particular attention to the interrelationship of bladder herniations with inguinal hernias.

Postsurgical outcomes assessment following varicocele ligation: laparoscopic versus subinguinal approach.

OBJECTIVES: To prospectively compare and objectively assess the postsurgical outcome parameters of both laparoscopic and open subinguinal techniques for varicocele ligation in infertile men. METHODS: A total of 41 evaluable patients with a history of infertility, abnormal semen analysis, and clinically diagnosed varicoceles underwent surgical ligation either by the insufflative intraperitoneal laparoscopic (n = 15), gasless laparoscopic (n = 7), or the open subinguinal (n = 19) approach. Most procedures (39 of 41) were performed in the outpatient setting, and patients were followed postoperatively for a minimum of 6 months. Postsurgical outcome was assessed by physical examination and review of a patient questionnaire quantifying the graded pain severity, analgesic requirements, and number of days to return to work. RESULTS: The average operative time was 82.3 +/- 26.5 minutes for insufflative intraperitoneal laparoscopic varicocelectomy, 170 +/- 55 minutes for gasless laparoscopic varicocelectomy, and 35.6 +/- 13.5 minutes for the open subinguinal approach. The analgesic requirement was 13.7 +/- 9.9 tablets for the insufflative laparoscopic group, 22.5 +/- 11 tablets for the gasless laparoscopic group, and 10.9 +/- 10.3 tablets for the open subinguinal group. The average number of days to return to work was 4.9 +/- 2.7 for the insufflative group, 6.6 +/- 2.6 for the gasless group, and 5.1 +/- 3.7 for the open subinguinal group. CONCLUSIONS: These results show no superiority of laparoscopic techniques over the standard open subinguinal technique with respect to hospital stay, analgesic requirements, or return to work. Laparoscopic techniques require excessive operative time, may have attendant complications, and require general anesthesia, limitations that preclude their routine application in varicocele ligation. However, the laparoscopic approach may have a role in the setting of other concurrently performed laparoscopic procedures.

Contact neodymium:yttrium-aluminum-garnet laser ablation of the external sphincter in spinal cord injured men with detrusor sphincter dyssynergia.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of contact neodymium:yttrium-aluminum-garnet (Nd:YAG) laser external sphincterotomy as an alternative treatment of detrusor-external sphincter dyssynergia (DESD). METHODS: Twenty-two spinal cord injured men with video-urodynamically verified DESD underwent external urinary sphincter ablation using the contact Nd:YAG laser. Three patients with bladder neck obstruction required concurrent contact laser bladder neck incision. Preoperative urodynamic parameters of voiding pressure, bladder capacity, and residual urine were compared with those obtained 1 year postoperatively. RESULTS: Each procedure was performed with the Nd:YAG contact laser set at 40 to 50 W, with a total accumulated energy of 23,800 to 60,000 J for each patient. The mean duration of surgery was 45 +/- 21 minutes. Bladder voiding pressure decreased from 87 +/- 23 preoperatively to 47 +/- 11 cm H2O at 12 months (P < 0.01). Residual urine volume decreased significantly, from 122 +/- 77 to 33 +/- 19 mL at 12 months (P < 0.01), and bladder capacity remained unchanged at 174 +/- 84 and 230 +/- 92 mL (P = 0.57). Three patients were found to have recurrent sphincter obstruction 1 year after laser sphincterotomy. Two patients experienced complications associated with condom catheter urinary drainage and returned to the use of an indwelling catheter. One patient experienced diminished reflex erectile function postoperatively. No patient required blood transfusion. No deleterious effects on renal function or symptoms of autonomic dysreflexia were noted. CONCLUSIONS: External urinary sphincter ablation using the contact Nd:YAG laser compares favorably with electrosurgical techniques.

A comparative analysis of prostate-specific antigen gene sequence in benign and malignant prostate tissue.

OBJECTIVES: Different molecular forms of prostate-specific antigen (PSA) appear to be expressed by benign prostatic hyperplasia (BPH) compared with prostate cancer. These differences are not well understood and may arise from aberrant RNA splicing, altered protein glycosylation, or variant PSA complexing to macroglobulins. To our knowledge, a direct comparison of PSA mRNA sequences in BPH versus prostate cancer to account for these differences has not been reported. The purpose of this study was to compare the complete PSA mRNA gene sequences in benign and malignant prostate tissue to determine whether altered PSA phenotypes are a result of gene mutations and to compare the published PSA sequences. METHODS: Total RNA was extracted from 17 prostate specimens from 8 patients, including matched benign and malignant prostate tissue in 6 patients. The samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) of the PSA coding sequence and part of the 3' untranslated region. Directed DNA sequencing was performed on these fragments. RESULTS: The benign and malignant prostate tissue cDNA sequence data of both strands were aligned and a computer analysis revealed 100% match with no evidence of mutation in prostate cancer compared to normal tissue. Sequence analysis did not reveal point mutations or aberrant splicing in any of the samples, including the matched malignant and nonmalignant tissues. Comparison with published sequences revealed infrequent and inconsistent sequence differences. CONCLUSIONS: These findings suggest that the PSA gene expressed in malignant prostate tissue is the wild type. PSA structural alterations previously reported in the literature may occur through post-transitional mechanisms. A detailed understanding of the possible differences in the PSA gene sequence is essential as we develop newer techniques that utilize RT-PCR to perform molecular diagnosis and staging of prostate cancer.

Renal vein thrombosis presenting as renal mass.

The excretory urogram of patients with acute renal vein thrombosis typically demonstrates symmetric enlargement of the involved kidney. We report a case of renal vein thrombosis that presented as a discrete renal mass on excretory urography and abdominal computerized tomography. The entity of renal vein thrombosis is briefly reviewed along with the computerized tomography findings seen in this setting.

Color Doppler imaging in predicting the biologic behavior of prostate cancer: correlation with disease-free survival.

OBJECTIVES: We investigated the association of transrectal color Doppler imaging (CDI) signal detection in localized prostate cancer with biologic behavior as assessed by tumor Gleason grade, seminal vesicle invasion, capsular and margin status, and actuarial biochemical freedom from relapse. METHODS: From 1991 to 1996, transrectal ultrasound with CDI and biopsy was performed in 2718 men using a 7.0-MHz probe optimized to detect color-coded blood flow within the gland and along the capsular margin. Color flow was graded on a scale from 0 to 2+, with 0 and 1+ representing no detectable flow and normal flow, and 2+ indicating increased flow. Color flow maps were constructed in 47 men with clinically localized prostate cancer treated by radical prostatectomy (RP) and compared to their whole mount RP specimen step sections. RESULTS: Color flow detected within the index tumor was graded as 2+ in 22 of 47 patients and 0 or 1+ in the remaining 25. Tumors graded 2+ correlated with higher Gleason grade, higher incidence of seminal vesicle invasion, and higher relapse rate, with only 11 of 22 patients disease free based on undetectable prostate-specific antigen (PSA) levels. In contrast, 24 of 25 patients with tumors graded 0 or 1+ are free of biochemical relapse with a median follow-up of 30.9 months. Patients with increased flow were 10.2 times more likely to relapse even after correction for other prognostic variables. In addition, tumors with 2+ capsular flow correlated with a higher incidence of non-organ-confined disease. CONCLUSIONS: Color-coded Doppler flow within the tumor and overlying capsule appears to correlate with both tumor grade and stage, respectively. Detection and grading of color-coded flow within biopsy-proven cancers may identify patients with a high likelihood of biochemical relapse.

Transrectal ultrasound-guided biopsy causes hematogenous dissemination of prostate cells as determined by RT-PCR.

OBJECTIVES: To determine if transrectal ultrasound-guided (TRUS) prostate biopsy causes dissemination of prostate cells into the circulation as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) targeted against prostate-specific antigen (PSA) mRNA. METHODS: RT-PCR PSA analysis was performed before and after prostatic invasive manipulations in 50 men. The cases consisted of 47 patients with TRUS and 3 with transurethral resection of the prostate (TURP). Peripheral venous blood (8 mL) was drawn before and within 60 minutes after the procedure. Total RNA was extracted from fractionated blood, and RNA/cDNA quality was assured and normalized with beta-actin RT-PCR analysis. The PSA primers hybridize exons 3 and 5, yielding a 254-basepair PCR product. The assay detects one LNCaP cell in a background of 100 million lymphoid cells and a single copy of PSA cDNA on an ethidium bromide gel. RESULTS: Among the 47 TRUS cases, 43 specimens were evaluable. Forty-two cases were negative before biopsy; among these patients, 4 cases (9.5%) converted to a positive RT-PCR PSA result. Both benign and malignant TRUS biopsies were capable of producing a positive RT-PCR PSA signal implicating iatrogenic dissemination of cells. All three TURP cases converted from a negative to a highly intense positive signal. CONCLUSIONS: We conclude that a positive RT-PCR PSA signal may result from release of prostate cells into the peripheral circulation after a TRUS biopsy and TURP. TURP causes greater dissemination than TRUS. Based on these preliminary data, we recommend that future molecular staging studies should be based on blood specimens drawn before performance of TRUS biopsy. This may be an important mechanism of prostate cancer dissemination meriting further investigations.