<p>Depletion of FZR1 leads to BRAF stabilization and subsequent ERK activation. Supplementary Figure S2. Depletion of FZR1 triggers the onset of premature senescence in primary melanocytes. Supplementary Figure S3. APCFZR1 promotes BRAF ubiquitination and subsequent degradation in a D-box dependent manner. Supplementary Figure S4. FZR1 disrupts the BRAF dimerization process. Supplementary Figure S5. Phosphorylation of FZR1 N-terminus by ERK and CYCLIN D1/CDK4 inhibits the APCFZR1 E3 ubiquitin ligase activity. Supplementary Figure S6. Pharmacologically inhibiting BRAF/ERK and CDK4 restores the APCFZR1 E3 ligase activity. Supplementary Figure S7. Depletion of FZR1 co-operates with PTEN deficiency to promote co-activation of BRAF/ERK and AKT oncogenic signaling both in vitro and in vivo. Supplementary Table S1. Mutation and deletion of FZR1 and 14 APC core complex subunits identified in melanoma patients from the TCGA melanoma dataset (cbioportal.org).</p>
ABSTRACT Objectives: To assess the rate of acute complications after radical retropubic prostatectomy (RRP) using contemporary surgical techniques and perioperative care. Materials and Methods: We reviewed the records of 306 consecutive patients who underwent RRP with or without bilateral pelvic lymph node dissection under low‐thoracic epidural anesthesia between October 1996 and April 1999. A standardized postoperative regimen was employed including early ambulation, epidural analgesia, and liquid diet the day after surgery. Results: The median length hospital stay was two nights. Acute complications occurred in 25 (8.2%) of 306 patients and were mostly minor. No thromboembolic or pulmonary events were noted, and there were no deaths. The 30‐day hospital readmission rate was 0.3%. Conclusion: The contemporary regimen of perioperative management employed in this series of men undergoing RRP results in short hospital stay and a low rate of primarily minor complications.
We developed models to predict post-laparoscopic radical or simple nephrectomy (LapNx) and post-laparoscopic partial nephrectomy (LapPNx) hospital duration of stay (DOS).We performed a retrospective review (design group) of all 726 patients (July 1997 to April 2004) who underwent LapNx or LapPNx at the Cleveland Clinic Foundation (CCF). Preoperative findings were recorded. Neural network algorithms were designed to predict the DOS before surgery. The models were then tested on a separate 252 patients from 6 different institutions, namely Tulane University Medical School, University of Arkansas for Medical Sciences, Cedars-Sinai Medical Center, University of Iowa, Mayo Clinic at Scottsdale and CCF.In the CCF design groups, the LapNx model accuracy was 73% to 74% and the LapPNx model 73% to 83%. Overall accuracy in the test groups at all 6 institutions was 72% (area under ROC 0.6 to 0.7) for the LapNx model and 52% to 81% (ROC 0.5 to 0.7) for the LapPNx model.The LapNx model provides 72% accuracy in predicting the DOS at all 6 institutions. The LapPNx model provided fair accuracy only at CCF and Tulane University Medical School. These models may streamline the delivery of care and continued testing will allow for further refinement.