"Robot-assisted partial nephrectomy: Evaluation of learning curve for an experienced renal surgeon." Journal of Endourology.24,1. 57-61. (2010 Conclusions: The learning curve for RAPN is short for surgeons already experienced with LPN. The learning curve for portions performed under warm ischemia is slightly longer, implying that the critical portions of the procedure require more experience to become facile. Tumor size does not appear to have a significant impact on the learning curve for surgeons experienced with LPN.
Despite early detection programs, many patients with prostate cancer present with intermediate- or high-risk disease. We prospectively investigated whether 11C-acetate PET/CT predicts lymph-node (LN) metastasis and treatment failure in men planned for radical prostatectomy. Methods 107 men with intermediate-or-high-risk localized prostate cancer with negative conventional imaging underwent PET/CT with 11C-acetate. Five underwent LN staging only and 102 LN staging and prostatectomy. PET/CT findings were correlated with pathologic nodal status. Treatment-failure-free survival (TFFS) was estimated by Kaplan-Meier method. The ability of PET/CT to predict outcomes was evaluated by multivariate Cox proportional hazards analysis. Results PET/CT was positive for pelvic LN or distant metastasis in 36 of 107 patients (33.6%). LN metastasis was present histopathologically in 25 (23.4%). The sensitivity, specificity, positive- and negative-predictive values of PET/CT for detecting LN metastasis were 68.0%, 78.1%, 48.6% and 88.9% respectively. 64 patients failed: 25 with metastasis, 17 with persistent post-prostatectomy prostate specific antigen (PSA) >0.20 ng/mL, and 22 with biochemical recurrence (PSA >0.20 ng/mL after nadir) during follow-up for a median of 44.0 months. TFFS was worse in PET-positive than in PET-negative patients (p<0.0001) and in those with false-positive versus true-negative scans (p<0.01), suggesting that PET may have demonstrated nodal disease not removed surgically or identified pathologically. PET positivity independently predicted failure in preoperative (hazard ratio=3.26, p<0.0001) and postoperative (HR=3.07, p=0.0001) multivariate models. Conclusion In patients planned for or completing prostatectomy, 11C-acetate-PET/CT detects LN metastasis not identified by conventional imaging and independently predicts TTFS.
Transcription factor nuclear factor-kappaB (NF-kappaB) is held in the cytoplasm in an inactive state by IkappaB inhibitors. Oncogenic activation of NF-kappaB is achieved by stimulus-induced ubiquitination and subsequent proteasome-mediated degradation of IkappaBalpha. Once released from the inhibitor, NF-kappaB/p65 enters the nucleus. A pre-requisite for cytokine-induced IkappaBalpha ubiquitination and degradation is the phosphorylation of IkappaBalpha at S32/S36. Phosphorylation of IkappaBalpha alone, however, is not sufficient to trigger its degradation, suggesting other events must be required for regulating IkappaBalpha degradation. In this study, we tested the hypothesis that phosphorylation of p65 at 536 is required for TNF-alpha induced IkappaBalpha proteolysis that in turn controls p65 nuclear translocation. We observed that, without affecting IkappaBalpha phosphorylation, MEK1 inhibitor U0126 treatment inhibited not only p65-S536 phosphorylation but also TNF-alpha-induced polyubiquitination of IkappaBalpha thereby inhibiting IkappaBalpha degradation. With p65 S536 phosphorylation mutants and mimics, we further observed that the structural mutation of p65 serine 536 to alanine inhibited the recruitment of ubiquitin to the p65-containing complex. As a consequence of suppressing polyubiquitination of the p65-containing complex, degradation of p65 phosphorylation mutant-bound IkappaBalpha was also inhibited. Accordingly, the nuclear translocation of phosphorylation-impaired p65 was significantly reduced. These findings suggest that p65 phosphorylation plays a key role in stimulus-induced IkappaBalpha ubiquitination.
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