[Non-invasive urine tests in diagnosis and as prognostic markers for urinary bladder carcinoma. Comparison of the BTAstat and NMP 22 tests with immunocytology using monoclonal antibodies against Lewis X and 486p3/12]. / Nichtinvasive Urintests in der Diagnostik und als Prognosemarker beim Harnblasenkarzinom.

INTRODUCTION AND OBJECTIVES: The non-invasive detection of urothelial carcinoma remains challenging. The aim of this study was the prospective evaluation of urine markers for bladder carcinoma. We compared the NMP 22 and BTAstat tests with immunocytology (IC) using monoclonal antibodies against the Lewis X antigen and against 486p3/12. METHODS: NMP 22 and BTAstat were performed on urine samples, and IC with 486p3/12 and Lewis X staining was performed on urine samples as well as bladder wash specimens ( n=146) in patients ( n=115) undergoing transurethral resection on suspicion of bladder cancer (70 specimens) or follow up cystoscopy because of a history of bladder cancer (76 specimens). Bladder cancer was detected in 54 patients (pTa: n=25, pT1: n=20, pT2: n=8, CiS: n=1). Cut-off levels were 10 U/ml for the NMP 22, 30% positive cells for 486p3/12, and 5% positive cells for the Lewis X test. RESULTS: The BTAstat test was positive in 65 (44.5%) cases, the NMP 22 in 69 (47.3%) cases, IC with 486p3/12 and the Lewis X was positive in 52 (35.6%) and 109 (74.7%) cases, respectively. Sensitivity was 70.3% (BTAstat), 68.5% (NMP 22), 94.4% (Lewis X), and 68.5% (486p3/12), respectively. The specificity was 70.6% (BTAstat), 65.2% (NMP 22), 36.9% (Lewis X), and 83.6% (486p3/12), respectively. Among the patients with a false positive test 2/22 (9.0%) patients (BTAstat), 2/25 (8%) patients (NMP 22 test), 4/43 (9.3%) patients (Lewis X), and 3/11 (27%) patients (486p3/12), respectively, suffered from tumor recurrence. In contrast, among the patients with a correct negative test 2/39 (2.0%) (BTAstat), 2/36 (0.5%) (NMP 22), 0/18 (0%) (Lewis X), and 1/50 (2.0%) (486p3/12), respectively, suffered from tumor recurrence. CONCLUSIONS: IC with the Lewis X revealed a higher sensitivity than all of the tested, commercially available methods. Because of its high sensitivity and its high negative predictive value, the Lewis X test may be useful for screening a high-risk population. Patients with a false positive 486p3/12 test have an increased risk of tumor recurrence when compared with patients with a correct negative test.

[Suprarenal leiomyoma of the vena cava. A rare differential adrenal gland tumor diagnosis]. / Suprarenales Leiomyom der Vena cava. Eine seltene Differenzialdiagnose eines Nebennierentumors.

Leiomyomas are benign tumors that can arise in the smooth muscle and can appear practically everywhere; hence, they must be taken into consideration as a rare possibility in the differential diagnosis of numerous tumors. While leiomyomas of the peripheral vessels are a relatively common finding, they are rarely found in the central vessels. Only a few cases of leiomyomas in the vena cava are known. In contrast to malignant leiomyosarcomas, leiomyomas usually grow towards the lumen. We report on the rare case of a leiomyoma in the inferior vena cava that appeared in the image to be located in the adrenal gland. Therefore, transperitoneal extirpation of the site was undertaken. It was only during surgery that a tumor emanating from the vessel wall became apparent. Thus, after an initial laparoscopic approach it became necessary to change to open resection of the tumor with cavotomy and resection of the vessel wall. The histopathological work-up revealed a benign leiomyoma and further imaging diagnostics gave no indication for the presence of metastases.

Elevated tissue expression of hyaluronic acid and hyaluronidase validates the HA-HAase urine test for bladder cancer.

PURPOSE: We examined the expression of 2 bladder tumor markers, hyaluronic acid (HA) and hyaluronidase (HAase), in bladder tissues and correlated tissue staining with the inferences of the HA-HAase urine test, which detects bladder cancer. MATERIALS AND METHODS: A biotinylated HA binding protein and an antiHYAL1 antibody were used to localize HA and HYAL1 type HAase, respectively, in 83 bladder tissues. Immunoblot analysis was performed using an antiHYAL1 antibody to detect HYAL1. RESULTS: A total of 12 normal bladder tissues showed no (66%) to 1+ (34%) HA staining and 0 (83%) to 1+ (17%) HYAL1 staining. The staining intensity of HA and HYAL1 increased in 71 bladder tumor specimens on chi-square analysis (p <0.001). Grade 1 tumors demonstrated 1+ (50%) to 2+ (50%) staining for HA and 1+ to 3+ staining for HYAL1 (37%, 37% and 26%, respectively). Grades 2 and 3 tumors showed 2+ to 3+ HA (94%) and HYAL1 (79%) staining. HA was expressed in tumor associated stroma and in tumor cells, whereas only tumor cells expressed HYAL1. In bladder tumor tissues HYAL1 expression was confirmed by immunoblot analysis. In 33 of the 34 patients (97%) with bladder cancer from whom urine and tumor tissue specimens were obtained at the same time 2+ to 3+ staining of HA and/or HYAL1 in 12 and 21, respectively, constituted a positive HA-HAase urine test (kappa = 0.945). CONCLUSIONS: To our knowledge this is the first report of HA localization in bladder tissues and of HYAL1 in any normal or tumor tissue. A close correlation of elevated HA and HYAL1 levels in tumor tissues with a positive HA-HAase urine test indicates that in patients with bladder cancer tumor associated HA and HYAL1 are secreted in urine, causing the HA-HAase test to be positive.

[Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers]. / Hyaluronsäure und Hyaluronidase. Zwei neue Blasenkarzinommarker.

The heterogeneity of bladder cancer concerning progress of recurrence is an essential characteristic of this disease. Hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are intricately associated with bladder cancer angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine. In 513 urine specimens (261 bladder cancer patients, 252 patients without bladder cancer) and 83 bladder tissue specimens (71 bladder tumors, 12 normal bladder tissues), the accuracy of HA and HAase as tumor markers was studied. Elevated urinary HA levels (> or = 500 ng/ml), indicating a positive HA test, suggest the presence of bladder cancer regardless of tumor grade. Elevated urinary HAase levels (> or = 10 mU/mg) indicate high-grade (G2/G3) bladder cancer. The combined HA-HAase urine test showed 91% sensitivity and 84% specificity to detect bladder cancer. The HA-HAase test is equally sensitive for monitoring tumor recurrence. Immunohistochemistry (IHC) staining of HA and HAase in the G1 and G2/G3 bladder cancer specimens was significantly (p < 0.001) higher than in normal bladder tissue. HA and HAase appear to be useful markers in the diagnosis of bladder cancer. When compared with other noninvasive tests, the HA-HAase urine test may be less expensive and more accurate.

Significance of high-grade prostatic intraepithelial neoplasia in needle biopsy specimens.

OBJECTIVES: To examine the significance of high-grade prostatic intraepithelial neoplasia (HGPIN) in biopsy specimens. METHODS: We performed sextant biopsies on a series of 83 cystoprostatectomy specimens removed for bladder cancer. For each case the number of foci and volume of both HGPIN and prostate cancer were assessed in the prostatectomy specimens and compared with the number of biopsy specimens involved by HGPIN. RESULTS: We identified HGPIN in 82 (99%) of 83 prostatic glands, whereas prostate cancer was found in 41 cases (49%). Corresponding sextant biopsies harbored both HGPIN and prostate cancer in 6 cases (7%), whereas only HGPIN was diagnosed in 29 sextant biopsies (35%). There was a positive correlation between the number of biopsy specimens containing HGPIN and the volume and multifocality of HGPIN in the corresponding prostatic glands. Prostates with HGPIN on sextant biopsy contained prostate cancer significantly more often when compared to cases with no HGPIN on sextant biopsy. Frequency of concurrent prostate cancer was higher in cases with two or more biopsy specimens containing HGPIN than in cases with only one such biopsy specimen, but case numbers of these categories were too small to render this difference statistically significant. CONCLUSIONS: The presence of HGPIN in sextant biopsies is a significant predictor of concurrent prostate cancer. Multifocality of HGPIN is a useful parameter in assessing the extent of HGPIN in the corresponding prostates. Its value in predicting a significantly increased risk of concurrent prostate cancer needs to be further investigated in larger case studies.

Detection rate of histologically insignificant prostate cancer with systematic sextant biopsies and fine needle aspiration cytology.

PURPOSE: We evaluate the detection rate of insignificant prostate cancer and the rate of significant prostate cancer overlooked in the results of systematic sextant biopsy and fine needle aspiration biopsy of the prostate of asymptomatic men with serum prostate specific antigen concentrations less than 4.0 ng./ml. MATERIALS AND METHODS: We analyzed specimens from 133 consecutive patients with a mean age of 60 years undergoing cystoprostatectomy for bladder cancer. Six systematic biopsy specimens and 2 fine needle aspiration cytology samples were taken from the prostate immediately after cystoprostatectomy. The specimens were step sectioned and examined for prostate cancer. Insignificant prostate cancer was defined as any cancer with an aggregate volume 0.5 cm.3 or less. RESULTS: Incidental prostate cancer was found in 58 of the 133 patients (44%). Tumor volume was 0.5 cm.3 or less in 47 cases. Sextant biopsy detected 7 cancers, including 4 of 47 (9%) that were insignificant and 3 of 11 (27%) that were significant. Fine needle aspiration cytology also detected 7 cancers, including 3 (6%) and 4 (36%) that were insignificant and significant, respectively. CONCLUSIONS: Systematic sextant biopsy and fine needle aspiration cytology each diagnose prostate cancer in about 5% of asymptomatic men who have normal digital rectal examination and serum prostate specific antigen less than 4.0 ng./ml. However, many of the cancers thus detected are insignificant and most of the significant cancers are missed. Therefore, routine screening of such patients with sextant biopsy or aspiration cytology does not appear to be justified.

Local intratumor immunotherapy of prostate cancer with interleukin-2 reduces tumor growth.

BACKGROUND: This study was designed to determine the effectiveness and toxicity of local continuous immunotherapy for prostatic cancer. METHODS: 60 juvenile male Copenhagen rats with Dunning adenocarcinoma of the prostate, implanted subcutaneously into both flanks after proven tumor growth, were treated with either human interleukin-2 (IL-2) depot preparations (n = 30) or albumin (placebo) depot preparations (n = 30) implanted directly next to tumor site. IL-2 depots released IL-2 reliably for more than 24 days. Rat serum was tested during treatment for human IL-2, possibly absorbed from depots, and for rat interferon gamma. RESULTS: IL-2 treatment reduced tumor growth significantly (p < 0.001) compared with albumin treated sites or untreated contralateral sites. No toxicity was observed during treatment. That neither human IL-2 nor rat interferon gamma was detected in serum indicates an exclusively local IL-2 effect. CONCLUSIONS: IL-2 depot preparations reduce tumor growth in Dunning adenocarcinoma of the prostate significantly without toxicity.