We strongly recommend extended radical lymphadenectomy to all patients undergoing radical cystectomy for bladder cancer to remove all metastatic tumor deposits completely. The operation can be conducted in routine clinical practice and our data may serve as a guideline for future standardization and quality control of the procedure.
Purpose: The HER2 oncogene is involved in the biology of many different tumor types and serves as a prognostic marker and a therapeutic target in breast cancer. In contrast to breast cancer, studies on Her2 overexpression and gene amplification in prostate cancer have yielded different results. The purpose of this study was to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in prostate cancer.Experimental Design: A tissue microarray containing >2,000 prostate cancers with follow-up data was used. Tissue microarray sections were analyzed on protein and DNA level using two different antibodies (HercepTest, DAKO; Novocastra NCL-CB11) and fluorescence in situ hybridization.Results: Immunohistochemical analyses showed highly similar results for both antibodies. Detectable Her2 immunostaining was observed in 17.2% for the HercepTest and in 22.5% for the Novocastra antibody with the vast majority of cases showing 1+ or 2+ staining. For both antibodies (HercepTest/ Novocastra), significant associations were found between positive staining and high Gleason grade (P < 0.0001, both), advanced pT stage (P < 0.0001/P = 0.0015), rapid tumor cell proliferation (P = 0.0004/P = 0.0071), and tumor recurrence (P < 0.0001, both). HER2 amplification was only found in 1 of 2,525 analyzable cases (0.04%).Conclusions: Low-level Her2 overexpression occurs at relevant frequency in prostate cancer and in the absence of gene amplification. Increased Her2 expression may potentially lead to an aggressive behavior of tumor cells through the stimulation of tumor cell proliferation because Her2 staining was shown to be significantly associated with Ki67 labeling index. These data argue for reconsidering anti-Her2 therapy, possibly with modified approaches. Clin Cancer Res; 16(5); 1553-60. ©2010 AACR.The Her2 protein, a transmembrane tyrosine kinase growth factor receptor, is found in normal and malignant epithelial cells and is involved in regulation of cell proliferation and differentiation (1). Her2 is well known as a strong prognostic factor and a successfully used therapeutic target in breast cancer (2). In 15% to 20% of breast cancer cases, Her2 is overexpressed as a consequence of gene amplification (2-4). Overexpressed Her2 protein serves as the therapeutic target for trastuzumab, a humanized monoclonal antibody (5, 6), which is now used both in a metastatic setting and as an adjuvant therapy of Her2-positive breast cancer.Many other tumor types, including prostate cancer, express increased levels of Her2, and evidence accumulates that trastuzumab can also be effective in Her2-positive tumors other than breast cancer. In previous studies, widely divergent rates for Her2 expression and amplification in primary prostate cancers have been reported. Rates of positivity range from 0% to 100% in immunohistochemical studies (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and from 0% to 53% in amplification analyses (18,(22)(23)(24). Most likely, these conflicting data are due...
Purpose: Deletions of 8p and gains of 8q belong to the most frequent cytogenetic alterations in prostate cancer. The target genes of these alterations and their biological significance are unknown.Experimental Design: To determine the relationship between chromosome 8 changes, and prostate cancer phenotype and prognosis, a set of 1.954 fully annotated prostate cancers were analyzed in a tissue microarray format by fluorescence in situ hybridization.Results: Both 8p deletions and 8q gains increased in number during different stages of prostate cancer progression. 8p deletions/8q gains were found in 26.1%/4.8% of 1,239 pT 2 cancers, 38.5%/9.8% of 379 pT 3a cancers, 43.5%/8.9% of 237 pT 3b cancers, 40.7%/14.8% of 27 pT 4 cancers, 39.1%/34.8% of 23 nodal metastases, 51.9%/33.3% of 27 bone metastases, and 45.5%/59.9% of 22 hormone refractory cancers (P < 0.0001 each). Both 8p deletions and 8q gains were also significantly associated with high Gleason grade and with each other (P < 0.0001 each). In primary tumors, 8p deletions were seen in only 27.3% of 1,882 cancers without 8q gain but in 57.4% of 122 tumors with 8q gain (P < 0.0001). Among cancers treated with radical prostatectomy, 8p deletions (P = 0.003) and 8q gains (P = 0.02) were associated with biochemical tumor recurrence. However, multivariate analysis (including prostate-specific antigen, pT/pN stage, Gleason score, and surgical margin status) did not reveal any statistically independent effect of 8p or 8q alterations on biochemical tumor recurrence.Conclusions: 8p deletions and 8q gains are relatively rare in early stage prostate cancer but often develop during tumor progression. The prognostic effect does not seem to be strong enough to warrant clinical application. Clin Cancer Res; 16(1); 56-64. ©2010 AACR.Prostate cancer is the most frequently diagnosed malignancy and the second most frequent cause of cancerrelated death among western males (1).Currently, clinical prediction tools rely solely on clinical (clinical stage), serologic (prostate-specific antigen), and histologic variables (Gleason grading; ref. 2).Because the development and progression of cancer is driven by molecular alterations, the analysis of molecular features may eventually allow better prediction of the behavior of individual cancers.Alterations on the DNA level would be especially suitable as prognostic markers. DNA alterations have the advantage of being less vulnerable to perioperative and postoperative ischemia or fixation procedures than RNA or proteins (3, 4). Deletions of 8p and gains of 8q are among the most frequent genomic alterations in prostate cancer. Several studies have proposed a relationship between 8p−/8q+ with adverse histopathologic findings (5-11). Studies suggesting associations with prostatespecific antigen progression, however, were limited to <100 cancers (12)(13)(14). Whereas considerable evidence points toward a role of chromosome 8 changes in prostate cancer biology, it is also evident that much larger patient cohorts are now needed to further cl...
Introduction Results for prosthesis implantation from everyday clinical practice within Europe are few. This report provides data on the most commonly used penile prostheses (the American Medical Systems [AMS] series). Aim The study aimed to assess, retrospectively, complications and patient satisfaction with AMS penile implants in 253 consecutive patients with erectile dysfunction from three European centers. Methods Pre, intra- and postoperative data were obtained from chart review, with a mean follow-up of 60 months; 200 patients were available for evaluation. Patient satisfaction data were collected using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. Main Outcome Measure Complications and patient satisfaction were assessed. Patient satisfaction was evaluated using a standardized assessment tool (the modified EDITS questionnaire). Results Major postoperative complications occurred in 40 (20%) patients, including 9 (22.5%) prosthesis infections, 18 (45%) mechanical failures, and 13 (32.5%) erosions. Patient satisfaction with the AMS 700CX, AMS Ambicor, and AMS 600-650 was 97%, 81%, and 75%, respectively; dissatisfaction was 0%, 5%, and 6%, respectively. Partner satisfaction with the AMS 700CX, AMS Ambicor, and AMS 600-650 was 91%, 91%, and 75%, respectively; dissatisfaction was 0%, 5%, and 6%, respectively. Erections were more natural (harder) than before with the AMS 700CX, AMS Ambicor, and AMS 600-650 in 91%, 85%, and 88%, respectively; hardness was the same as before in 9%, 15%, and 13%, respectively; no erections were less hard than before. Conclusions Postoperative complications differed from those reported in the literature, while patient satisfaction rates were roughly similar. The reporting of specific data for different implant types, plus the use of standardized assessment tools for patient satisfaction is significant as in the future, it will allow comparison of data between centers performing penile prosthesis implants using these devices.
A low pressure rectosigmoid reservoir for urine is created obviating the need for colostomy, augmentation or extensive bowel surgery. Antimesenteric splitting of the intestine at the rectosigmoid junction and subsequent side-to-side anastomosis are performed. Urodynamic data demonstrate that the detubularization is effective in rendering high pressure bowel contractions ineffective. Without the risk of damaging the mesentery the pouch is fixed at the promontory, which lessens the risk of ureteral kinking and upper urinary tract dilatation. The technique is indicated not only in cases of failed ureterosigmoidostomy but also for primary urinary diversion. All 47 patients who underwent the operation were evaluable with a followup of 1 to 20 months (mean 10 months). All patients are continent during the daytime with a mean emptying frequency of 5 times. All but 1 elderly woman are dry at night with a mean frequency of 1 episode. With the reservoir full the basal pressure was 24 cm. water and the highest peak pressure recorded was 35 cm. water. The low pressure improves continence, protects the upper urinary tract and even allows dilated ureters to be implanted.
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