Ursula Kuehs

The periprostatic autonomic nerves--bundle or layer?

BACKGROUND The functional outcome of a nerve-sparing radical prostatectomy (RP) depends on the knowledge of autonomic nerve distribution in correlation to the prostate. OBJECTIVE Recent literature has focused predominantly on the anterior prostate; this study evaluates the nerve distribution on the entire prostate, using a two-dimensional approach. DESIGN, SETTING, AND PARTICIPANTS From 17 non-nerve-sparing (NS) RP specimens, 77 whole mounted serial sections were immunostained with PGP9.5 and analyzed. INTERVENTION Each prostate half was divided into 12 sectors (three levels: apex, mid-part, base; four courses: anterior, anterolateral, posterolateral, posterior). MEASUREMENTS The extracapsular nerves were counted and classified by size (>200microm or <or=200microm). RESULTS AND LIMITATIONS Approximately two-thirds of the nerves were located in the posterolateral while 26.3/27.0% were located in the anterior and anterolateral. In the anterolateral, along the base-apex direction, the nerves decreased whereas they increased in the posterior. In the anterior, the highest counts were found in the mid-prostate. PGP 9.5 stain helps to determine the extracapsular nerve distribution, however, it does not allow a functional allocation. CONCLUSIONS The nerve course expands from the base in the mid-part to the anterior sector, before it narrows towards the apex in the posterior lateral and posterior sectors. Therefore, it is recommended that the surgeon focus on nerve preservation in particular at the apex, starting in the anterior at the mid section as well as the common posterolateral course.

Activation of PI3K Is Associated with Reduced Survival in Renal Cell Carcinoma

Objectives: The epidermal growth factor receptor- (EGFR) activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt) pathway is associated with tumorigenesis and progression. The aims of the present study were to determine the expression patterns of Akt pathway parameters PI3K, phosphatase and tensin homolog (PTEN), phosphor-Akt (p-Akt) and their combination, for their possible prognostic value in renal cell carcinoma (RCC). PTEN dephosphorylates the liquid product of PI3K. Methods: Tumor samples from 176 RCC patients were investigated for PTEN, p-Akt and PI3K expression by immunohistochemistry. Expression levels were correlated to clinical variables and postoperative outcome by uni- and multivariate statistical analysis. Results: The various expression levels within the tumor samples were independent of histological grade and tumor stage, due to different levels of activation of the PI3K/p-Akt pathway. The activation of PI3K protein was found to be significantly associated with reduced survival times (p = 0.0304, multivariate analysis). Analysis of combined biomarker expressions showed that decreased long-term survival was correlated with PTEN low/p-Akt high expression (p < 0.05). Conclusions: Activation of the PI3K pathway is significantly associated with adverse clinical outcome in RCC. Analysis of biomarker combinations might identify high-risk patients and a subsequent need to adapt treatment modalities. Molecular pathways regulating PI3K activation appear to be promising targets for drug development in the clinical management of RCC patients.

Combined application of cytology and molecular urine markers to improve the detection of urothelial carcinoma

The sensitivity of cytology for the detection of urothelial carcinoma (UC) is limited. Newer methods such as fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and protein markers have been developed to improve urine‐based detection of UC. As only little is known regarding the combined application of these markers, we investigated whether combinations of 4 of the most broadly available tests (cytology, FISH, uCyt+, and nuclear matrix protein 22 [NMP22‐ELISA]) may improve their diagnostic performance.

Topographical Sensitivity and Specificity of Endorectal Coil Magnetic Resonance Imaging for Prostate Cancer Detection

Objectives: Endorectal coil magnetic resonance imaging (EC-MRI) is useful to evaluate prostate cancer localization. Herein, we evaluate sensitivity and specificity of EC-MRI in different regions of the prostate by comparing the acquired images to whole-mount sections of the prostate after radical prostatectomy. Methods: 69 patients with localized prostate cancer were included. After virtually dividing the prostate into 12 sectors, results of EC-MRI were compared to corresponding whole-mount sections by contingency analysis. Sensitivity and specificity were calculated for each of the 12 areas as well as for the dorsal and ventral region. Results: Sensitivity right/left was dorsal apex/mid/base 41/41, 60/67 and 73/79%; ventral 33/52, 43/42 and 47/52%. Specificity right/left was dorsal apex/mid/base 92/89, 82/75 and 88/69%; ventral 100/100, 100/92 and 88/83%. Local sensitivity and specificity regarding dorsal versus ventral was 88/100 and 65/87%. Conclusions: Local sensitivity decreased from basodorsal to apicoventral direction, whereas local specificity increased in the same direction. Therefore, prostate cancers demonstrated by MRI are more prone to be detected in the basodorsal region, whereas less false-positive results are found in the apicoventral region. These variations in topographical specificity and sensitivity need to be considered before radical prostatectomy or MRI-guided biopsy.

Influence of Renal Excretory Function on the Performance of Urine Based Markers to Detect Bladder Cancer

PURPOSE In hematuria cases urine based tests are used to detect bladder cancer, although the diagnostic yield remains insufficient due to influencing variables, including urinary tract infection. Many patients are elderly with renal insufficiency and have proteinuria as an additional influencing factor. To our knowledge no data are available on the accuracy of urine based bladder cancer tests in conjunction with renal function. MATERIALS AND METHODS Urine samples of 449 patients with hematuria and histology were included in analysis. Cytology, fluorescence in situ hybridization, immunocytology and nuclear matrix protein 22 assay were done. Renal function was classified as normal, impaired or severely impaired based on serum creatinine, the glomerular filtration rate and proteinuria. False-positive rates were statistically compared in regard to renal function. RESULTS A total of 382 patients did not have bladder cancer. There was an increased false-positive rate for creatinine and the glomerular filtration rate. The nuclear matrix protein 22 test showed a 22.0% and 46.7% false-positive rate in the normal and limited function cohorts, respectively (p = 0.05). Similar trends were noted for proteinuria. Indeterminate significance was detected, separating those with severely impaired function for immunocytology and those in the normal group for fluorescence in situ hybridization (p = 0.08 and 0.06, respectively). Proteinuria was a significant factor for urine cytology with increased false-positive results in the absence of urinary tract infection (p = 0.0017 and 0.05, respectively). CONCLUSIONS To our knowledge this is the first study of renal function and the accuracy of urine based bladder cancer markers. Renal function influences the diagnostic yield. A decreased glomerular filtration rate was associated with increased false-positive nuclear matrix protein 22 results while proteinuria decreased urine cytology specificity. Renal function should be considered when urine based bladder cancer tests are interpreted.

Impact of different grades of microscopic hematuria on the performance of urine-based markers for the detection of urothelial carcinoma

OBJECTIVE To evaluate the performance of urine cytology (CYT), the UroVysion test [(fluorescence-in-situ-hybridization (FISH)], the uCyt+-test, and the nuclear matrix protein 22 ELISA (NMP22) at different grades of microscopic hematuria (HU) in a cohort of 2,365 patients suspicious for urothelial cell carcinoma (UCC). PATIENTS AND METHODS A cohort of 2,365 consecutive patients suspected to have UCC underwent testing of at least 1 of the 4 noninvasive urine markers followed by cystoscopy, upper urinary tract imaging and, in case of suspicious findings, transurethral biopsy and/or resection of suspicious lesions. The grade of microscopic HU was determined by dipstick evaluation and urine microscopy and subdivided into 4 grades. The test results were compared with the HU status by contingency analysis and Cochran-Armitage test for trend separated for patients without evidence of UCC and with histologically proven UCC. RESULTS In case of grade 0, I, II, and III HU, rates of false positive CYT were 13.0, 17.4, 16.3, and 19.5% (P = 0.02), false negative CYT distributed 37.9, 18.5, 20.0, and 15.5% (P = 0.0003). FISH was false positive in 16.7, 19.8, 19.8, and 23.3% (P = 0.051) and false negative in 42.7, 27.5, 25.9, and 25.0% (P = 0.1). The uCyt+ was false positive in 12.5, 16.9, 24.0 and 35.1% (P < 0.0001), and false negative in 57.1, 26.4, 31.5, and 12.7% (P = 0.0003). NMP22 was false positive in 35.3, 55.3, 75.2, and 79.7% (P < 0.0001) and false negative in 50.0, 36.2, 22.6, and 8.2% (P < 0.0001). CONCLUSION The extent of microscopic HU significantly influences the performance of noninvasive urine markers for UC. False positive rates of CYT, uCyt+, and NMP22 significantly increase with the degree of HU whereas false negative results of CYT, uCyt+, and NMP22 are less frequent in patients with high grade microscopic HU. These results underline the relevance of the grade of HU for the appropriate interpretation of urine tests.

Quantification of tumor cell burden by analysis of single cell lymph node disaggregates in metastatic prostate cancer.

The size of lymph node (LN) metastases in prostate cancer patients represents an important prognosticator, but histological work‐up may not reflect the true extent of tumor invasion. We present a novel technique (1) to detect early tumor cell dissemination and (2) to quantify the true tumor burden.

Point-of-Care Tests for Bladder Cancer: The Influencing Role of Hematuria.

Introduction. Several point-of-care tests (POCT) are available for the diagnosis of bladder cancer (BC). We evaluate the impact of HU (hematuria) on performance of POCTs. Materials and Methods. Urine from 10 donors was diluted with blood from 0.5 to 0.00625%. BladderCheckR, BTAstatR, BCMR, and BTAR tests were applied. Tests were additionally conducted in 54 patients with HU. HU was stratified according to the amount of erythrocytes (RBC)/μL using two systems: (1) no HU; mild microscopic HU; severe microscopic HU; gross HU; (2) I <25 RBCs; <250 II; ≥250 III. Results were compared to HU status and histopathology. Results. Gross HU became evident between 2090 RBCs/μL and 1065/μL. Addition of blood led to default tests in all 4: BladderCheckR 0.25%; BCM 0.025%, BioNexia 0.00625%, and BTAstat <0.00625%. Rates of false positives for BladderCheck, BTAstat, BCM, and BioNexia were 5.9, 11.8, 0, and 1.8% without HU and 0, 66.7, 44.4, and 66.7% with HU. BTAstat, BCM, and BioNexia were independently influenced by HU (P < 0.0002). Conclusions. NMP22-BladderCheck was most resistant to blood. The diagnostic yield of all others was significantly influenced by HU. A well-defined HU grading helps to define limits of HU for a reliable interpretation of BC-POCTs.

Impact of Clinical Parameters on the Diagnostic Accuracy of Endorectal Coil MRI for the Detection of Prostate Cancer

Objectives: Endorectal coil MRI (endoMRI) of the prostate is useful to evaluate tumor localization. There is little evidence on patient characteristics affecting its diagnostic performance. We evaluate the influence of clinical and histological parameters on the accuracy of endoMRI. Methods: Sixty-nine patients with prostate cancer were included. After virtually dividing the prostate into pixels of 1 cm2, results of endoMRI were compared with those from prostatectomy specimens’ whole-mount sections. Univariate and multivariate analyses were performed to calculate the impact of clinical and histological parameters on the number of appropriately described pixels. Results: In 9, no tumor could be demonstrated by endoMRI. 48.3% of patients were staged correctly, 23.3% were over- and 28.3% understaged. Mean rates of correctly labeled pixels were 0.44 (± 0.04 SEM) for tumor and 0.90 (± 0.01) for benign segments. In univariate analysis, the rate of correctly labeled tumor segments showed significant positive correlations with Gleason score ≧7 and negative correlations with prostate weight and multifocality. The rate of correctly labeled benign segments showed significant negative correlation with tumor weight. All factors were independent variables in multivariate analysis. Conclusions: The reliability of endoMRI depends on clinical parameters. Higher Gleason scores, unifocal tumors and smaller prostate volumes ameliorate endoMRI performance.

Prospective assessment of histological serial sectioning of pelvic lymph nodes in prostate cancer: a cost-benefit analysis

Study Type – Therapy (case series)