Despite negative preoperative staging, pelvic lymphadenectomy and cystectomy for bladder cancer reveal a high percentage of unsuspected nodal metastases (24%) that have a 25% chance for long-term survival. This procedure also ensures a low pelvic recurrence rate even in lymph node-positive patients, and patients with locally advanced cancer have a 56% probability of 5-year recurrence-free survival.
Meticulous lymph node dissection reveals a high rate of metastases (25%). In patients with positive nodes time to progression is significantly correlated with the number of diseased nodes. Some patients with minimal metastatic disease remain free of prostate specific antigen relapse for more than 10 years after prostatectomy without any adjuvant treatment. Meticulous pelvic lymph node dissection, particularly in patients with micrometastases, seems not only to be a staging procedure, but may also have a positive impact on disease progression and long-term disease-free survival.
Bone morphogenic protein 7 (BMP7) counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity. Because epithelial-to-mesenchymal transition is involved in cancer, we investigated whether BMP7 plays a role in prostate cancer growth and metastasis. BMP7 expression in laser-microdissected primary human prostate cancer tissue was strongly down-regulated compared with normal prostate luminal epithelium. Furthermore, BMP7 expression in prostate cancer cell lines was inversely related to tumorigenic and metastatic potential in vivo and significantly correlated to E-cadherin/vimentin ratios. Exogenous addition of BMP7 to human prostate cancer cells dose-dependently inhibited transforming growth factor -induced activation of nuclear Smad3/4 complexes via ALK5 and induced E-cadherin expression. Moreover, BMP7-induced activation of nuclear Smad1/4/5 signaling transduced via BMP type I receptors was synergistically stimulated in the presence of transforming growth factor , a growth factor that is enriched in the bone microenvironment. Daily BMP7 administration to nude mice inhibited the growth of cancer cells in bone. In contrast, no significant growth inhibitory effect of BMP7 was observed in intraprostatic xenografts. Collectively, our observations suggest that BMP7 controls and preserves the epithelial phenotype
There were significant numbers of lymph node metastases at all 3 different areas of lymphadenectomy. Positive lymph nodes were found along the internal iliac artery in more than half (58%) of the patients and exclusively in 19%. Therefore, we consider lymph node dissection along the internal iliac (hypogastric) vessels essential for representative staging. Without this dissection a fifth of node positive cases would have been under staged and diseased nodes would have remained in more than half of the cases.
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