A. Fleischmann

Twenty years experience with an ileal orthotopic low pressure bladder substitute--lessons to be learned

PURPOSE We present the long-term results of a large consecutive series of patients undergoing ileal orthotopic bladder substitution following radical cystectomy. MATERIALS AND METHODS Between April 1985 and 2005 orthotopic bladder substitution with an ileal low pressure reservoir was performed in 482 patients (including 40 women) after radical and, if possible, nerve sparing cystectomy. In 447 cases the procedure was combined with an afferent ileal isoperistaltic tubular segment. The patients were followed prospectively. RESULTS In the 482 patients 61 early (less than 30 days) diversion related complications requiring prolonged hospital stay or readmission were noted and 115 late complications required treatment. At 1 year continence was good in 92% of patients during the day and in 79% at night. At last followup 93% of patients could void spontaneously. Of 442 evaluable men 99 (22.4%) reported having erections without and 68 (15.4%) with medical assistance. Ureteroileal stenosis was observed in 12 of 447 (2.7%) patients. Urethral recurrence was detected in 25 of 482 (5%) patients. A total of 15 (5%) patients received vitamin B12 substitution. Renal parenchyma decreased only in patients with preoperative or postoperative ureteral obstruction. After 10 years patients with normal renal function had no long-term acidosis and in 20 patients the incidence of osteoporosis resembled that of the normal population. CONCLUSIONS Ileal orthotopic bladder substitution combined with an afferent ileal tubular segment allows for good long-term functional results provided patients are restrictively selected, postoperative instructions are followed carefully, and typical complications such as outlet obstruction and hernias are treated early.

Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy.

PURPOSE We evaluate the outcome in patients with node positive bladder cancer with particular reference to the effect of individual characteristics of positive nodes on survival after meticulous pelvic lymphadenectomy at cystectomy. MATERIALS AND METHODS This prospective analysis contains 452 cases of bladder cancer staged preoperatively as N0M0, managed with pelvic lymphadenectomy and cystectomy between 1984 and 1997. A total of 83 (18%) patients with histologically confirmed node positive disease are included in our study. RESULTS The median overall survival of patients with positive nodes was 20 months. Median 5-year survival was 29%. Patients who survived were found with positive nodes at each site in the pelvis. The median survival of 57 patients with less than 5 positive nodes was 27 months, compared with 15 months for 26 with 5 nodes or more (log-rank test p = 0.0027). Median survival of 26 patients with no lymph node capsule perforation was 93 months, compared with 16 months for 57 with capsule perforation (p = 0.0004). The median survival of 18 patients with a maximum diameter of lymph node metastasis up to 0.5 cm. was 64 months, compared with 16 months for 65 with nodal metastasis greater than 0.5 cm. (p = 0.024). Contralateral positive nodes were found in 16 of 39 (41%) patients with unilateral bladder cancer. CONCLUSIONS Long-term survival is possible with node positive bladder cancer. Those patients with few as well as smaller and, therefore, unsuspected nodal metastases, and those without lymph node capsule perforation have the best results after removal of pelvic metastatic nodal disease. Because patients who survive may be found regardless of the site of pelvic nodal metastases, meticulous bilateral pelvic lymphadenectomy is warranted in all patients at the time of attempted curative cystectomy for bladder cancer, particularly if there is no clinical evidence of nodal involvement.

Nerve Sparing Open Radical Retropubic Prostatectomy—Does It Have an Impact on Urinary Continence?

PURPOSE We prospectively assessed the role of nerve sparing surgery on urinary continence after open radical retropubic prostatectomy. MATERIALS AND METHODS We evaluated a consecutive series of 536 patients who underwent open radical retropubic prostatectomy with attempted bilateral, unilateral or no nerve sparing, as defined by the surgeon, without prior radiotherapy at a minimum followup of 1 year with documented assessment of urinary continence status. Because outlet obstruction may influence continence rates, its incidence and management was also evaluated. RESULTS One year after surgery 505 of 536 patients (94.2%) were continent, 27 (5%) had grade I stress incontinence and 4 (0.8%) had grade II stress incontinence. Incontinence was found in 1 of 75 (1.3%), 11 of 322 (3.4%) and 19 of 139 patients (13.7%) with attempted bilateral, attempted unilateral and without attempted nerve sparing, respectively. The proportional differences were highly significant, favoring a nerve sparing technique (p <0.0001). On multiple logistic regression analysis attempted nerve sparing was the only statistically significant factor influencing urinary continence after open radical retropubic prostatectomy (OR 4.77, 95% CI 2.18 to 10.44, p = 0.0001). Outlet obstruction at the anastomotic site in 33 of the 536 men (6.2%) developed at a median of 8 weeks (IQR 4 to 12) and was managed by dilation or an endoscopic procedure. CONCLUSIONS The incidence of incontinence after open radical retropubic prostatectomy is low and continence is highly associated with a nerve sparing technique. Therefore, nerve sparing should be attempted in all patients if the principles of oncological surgery are not compromised.

Good outcome for patients with few lymph node metastases after radical retropubic prostatectomy.

BACKGROUND Conflicting results exist regarding the value of an extended pelvic lymph node dissection (PLND) in node-positive patients undergoing radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. OBJECTIVE To assess the long-term outcome in node-positive patients who underwent extended PLND followed by RRP. DESIGN, SETTING, AND PARTICIPANTS A consecutive series of 122 node positive patients with negative preoperative staging examinations, no neoadjuvant hormonal or radiotherapy, and who underwent extended PLND (>/=10 lymph nodes in the surgical specimen) followed by RRP were analyzed. None of the patients received immediate androgen deprivation therapy (ADT). INTERVENTION All patients underwent extended PLND followed by RRP. MEASUREMENTS Biochemical recurrence-free survival, cancer-specific, and overall survival were assessed using the Kaplan-Meier technique. RESULTS AND LIMITATIONS Median prostate-specific antigen (PSA) was 16ng/ml. At pathological examination 76% of the 122 patients had pT3-pT4 tumours, 50% seminal vesicle infiltration. A median of 22 nodes were removed per patient. Median cancer-specific survival at 5 and 10 yr was 84.5% and 60.1%, respectively. In patients with </=2 or >/=3 positive nodes removed, median cancer-specific survival at 10 yr was 78.6% and 33.4%, respectively (p<0.001). After a median period of 33 mo, 61 of the 122 patients (50%) received ADT, particularly those (69%) with >/=3 positive nodes removed. This retrospective study includes a significant percentage of patients with high tumour burden, and therefore may not reflect current patient series. CONCLUSIONS Patients with </=2 positive nodes detected after extended PLND followed by RRP had good long-term results and should not be denied treatment with curative intent. In contrast, prognosis was poor in patients with >/=3 positive nodes, despite extended PLND and despite ADT in 69% of patients.

Reliable gene expression measurements from degraded RNA by quantitative real-time PCR depend on short amplicons and a proper normalization

Quantitative reverse transcriptase real-time PCR (QRT-PCR) is a robust method to quantitate RNA abundance. The procedure is highly sensitive and reproducible as long as the initial RNA is intact. However, breaks in the RNA due to chemical or enzymatic cleavage may reduce the number of RNA molecules that contain intact amplicons. As a consequence, the number of molecules available for amplification decreases. We determined the relation between RNA fragmentation and threshold values (Ct values) in subsequent QRT-PCR for four genes in an experimental model of intact and partially hydrolyzed RNA derived from a cell line and we describe the relation between RNA integrity, amplicon size and Ct values in this biologically homogenous system. We demonstrate that degradation-related shifts of Ct values can be compensated by calculating delta Ct values between test genes and the mean values of several control genes. These delta Ct values are less sensitive to fragmentation of the RNA and are unaffected by varying amounts of input RNA. The feasibility of the procedure was demonstrated by comparing Ct values from a larger panel of genes in intact and in partially degraded RNA. We compared Ct values from intact RNA derived from well-preserved tumor material and from fragmented RNA derived from formalin-fixed, paraffin-embedded (FFPE) samples of the same tumors. We demonstrate that the relative abundance of gene expression can be based on FFPE material even when the amount of RNA in the sample and the extent of fragmentation are not known.

Extracapsular Extension of Pelvic Lymph Node Metastases From Urothelial Carcinoma of the Bladder Is an Independent Prognostic Factor

Purpose To analyze the prognostic impact of risk factors for urothelial carcinoma of the bladder (UCB) with pelvic lymph node (LN) metastases. Patients and Methods We analyzed a consecutive series of 507 patients with UCB who were preoperatively staged N0M0. One hundred one of 124 eligible patients who were treated with radical cystectomy and standardized extended bilateral pelvic lymphadenectomy with curative intent and had postoperatively confirmed LN metastases were evaluated in regard to recurrence-free and overall survival. Results A median of 22 nodes per patient (range, 10 to 43 nodes) were removed and examined. Median recurrence-free and overall survival durations were 17 months and 21 months (range for both, 1 to 191 months), respectively. In the multivariate analysis for recurrence-free survival, extracapsular extension of LN metastases was the strongest prognostic factor (P = .019). Other variables such as tumor stage (pT1/2 v pT3 and pT4), the number (< five v ≥ five), and the percentage (< 20...

Combined Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced and Diffusion-weighted Magnetic Resonance Imaging Facilitates Detection of Metastases in Normal-sized Pelvic Lymph Nodes of Patients with Bladder and Prostate Cancer

BACKGROUND Conventional cross-sectional imaging with computed tomography and magnetic resonance imaging (MRI) has limited accuracy for lymph node (LN) staging in bladder and prostate cancer patients. OBJECTIVE To prospectively assess the diagnostic accuracy of combined ultrasmall superparamagnetic particles of iron oxide (USPIO) MRI and diffusion-weighted (DW) MRI in staging of normal-sized pelvic LNs in bladder and/or prostate cancer patients. DESIGN, SETTING, AND PARTICIPANTS Examinations with 3-Tesla MRI 24-36 h after administration of USPIO using conventional MRI sequences combined with DW-MRI (USPIO-DW-MRI) were performed in 75 patients with clinically localised bladder and/or prostate cancer staged previously as N0 by conventional cross-sectional imaging. Combined USPIO-DW-MRI findings were analysed by three independent readers and correlated with histopathologic LN findings after extended pelvic LN dissection (PLND) and resection of primary tumours. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Sensitivity and specificity for LN status of combined USPIO-DW-MRI versus histopathologic findings were evaluated per patient (primary end point) and per pelvic side (secondary end point). Time required for combined USPIO-DW-MRI reading was assessed. RESULTS AND LIMITATIONS At histopathologic analysis, 2993 LNs (median: 39 LNs; range: 17-68 LNs per patient) with 54 LN metastases (1.8%) were found in 20 of 75 (27%) patients. Per-patient sensitivity and specificity for detection of LN metastases by the three readers ranged from 65% to 75% and 93% to 96%, respectively; sensitivity and specificity per pelvic side ranged from 58% to 67% and 94% to 97%, respectively. Median reading time for the combined USPIO-DW-MRI images was 9 min (range: 3-26 min). A potential limitation is the absence of a node-to-node correlation of combined USPIO-DW-MRI and histopathologic analysis. CONCLUSIONS Combined USPIO-DW-MRI improves detection of metastases in normal-sized pelvic LNs of bladder and/or prostate cancer patients in a short reading time.

Metallic magnetic calorimeters

Metallic magnetic calorimeters (MMC) are calorimetric particle detectors, typically operated at temperatures below 100 mK, that make use of a paramagnetic temperature sensor to transform the temperature rise upon the absorption of a particle in the detector into a measurable magnetic flux change in a dc‐SQUID. During the last years a growing number of groups has started to develop MMC for a wide variety of applications, ranging from alpha‐, beta‐ and gamma‐spectrometry over the spatially resolved detection of accelerated molecule fragments to arrays of high resolution x‐ray detectors. For x‐rays with energies up to 6 keV an energy resolution of 2.7 eV (FWHM) has been demonstrated and we expect that this can be pushed below 1 eV with the next generation of devices. We give an introduction to the physics of MMCs and summarize the presently used readout schemes as well as the typically observed noise contributions and their impact on the energy resolution. We discuss general design considerations, the micro‐fabrication of MMCs and the performance of micro‐fabricated devices. In this field large progress has been achieved in the last years and the thermodynamic properties of most materials approach bulk values allowing for optimal and predictable performance.

Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours.

BACKGROUND Her2, an alias for the protein of v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), might be an attractive therapeutic target in metastasising bladder cancer. Genotype and phenotype of primary tumours and their metastases may differ. OBJECTIVES Determine Her2 status in both tumour components to better assess the potential of anti-Her2 therapies. DESIGN, SETTING, AND PARTICIPANTS Histologic examination revealed lymph node metastases in 150 patients with urothelial bladder cancer clinically staged as N0M0. A tissue microarray was constructed with four tumour samples per patient: two from the primary tumour and two from nodal metastases. Her2 status was determined at the gene level by fluorescence in situ hybridisation (FISH) and at the protein level by immunohistochemistry (IHC). INTERVENTIONS All patients underwent cystectomy and standardised extended lymphadenectomy. MEASUREMENTS Overall survival was assessed according to HER2 gene status and protein expression in primary bladder cancers and lymph node metastases. RESULTS AND LIMITATIONS Her2 amplification was significantly more frequent in lymph node metastases (15.3%) than in matched primary bladder cancers (8.7%; p = 0.003). Her2 amplification in primary tumours was highly preserved in the corresponding metastases as indicated by only one amplified primary tumour without amplification of the metastasis. There was a high concordance in HER2 FISH results between both samples from the primary tumour (κ = 0.853) and from the metastases (κ = 0.930). IHC results were less concordant (κ=0.539 and 0.830). FISH and IHC results were poorly correlated in primary tumours (κ = 0.566) and metastases (κ = 0.673). While Her2 amplification in the primary tumour significantly predicted poor outcome (p = 0.044), IHC-based survival prediction was unsuccessful. CONCLUSIONS Her2 amplification in metastasising bladder cancer is relatively frequent, is homogeneous in each tumour component, and predicts early death. This suggests a high potential for anti-Her2 therapies. For patient selection, FISH might be more accurate than IHC.

Immunological microenvironment in prostate cancer: High mast cell densities are associated with favorable tumor characteristics and good prognosis

Number of intratumoral mast cells predicts survival in various cancers. The prognostic significance of such mast cells in surgically treated prostate cancer is unknown.