SMAD4 loss predicts worse overall and distant metastasis-free survival in patients with resected pancreatic adenocarcinoma.

BACKGROUND: In select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA-sequencing (RNA-seq) expression is a robust method for predicting overall survival (OS) and distant metastasis-free survival (DMFS) in patients with resected pancreatic adenocarcinoma. METHODS: Utilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I-III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA-seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA-seq via multivariable models and receiver operator characteristic curves. RESULTS: In TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00-2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87-2.03; p = .19). Low SMAD4 RNA-seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17-2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14-2.54; p = .009). In the ICGC, increased SMAD4 RNA-seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86-.94) and DMFS (AUC, .84; 95% CI, .82-.87). CONCLUSIONS: In patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA-seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA-seq expression may be a useful marker to predict metastatic spread.

Updated Review: The Steroid Controversy for Management of Spinal Cord Injury.

BACKGROUND: Acute spinal cord injury (ASCI) is a devastating event that can have a profound impact on the lives of patients and their families. While no definitive medical treatment exists, the role of methylprednisolone (MP) in the management of ASCI and other spinal cord pathologies has been investigated in depth; however, its use remains contentious. While MP initially showed promise in the efficacy of ASCI treatment, more recent studies have questioned its use citing numerous systemic adverse effects. Pharmacologic treatments in this area are poorly understood due to the scarcity of knowledge surrounding the pathophysiology and heterogeneity of patients presenting with these conditions. Despite these shortcomings and due to the lack of alternative treatment options, MP is still widely used by physicians. METHODS: We review prior and current literature on the use of MP treatment for ASCI patients with a discussion of novel drug delivery systems that have demonstrated the potential to improve MP's bioavailability at the site of injury while minimizing systemic side effects. In addition, current views on the role of MP and dexamethasone in metastatic spinal cord compression and postoperative infection are reviewed. RESULTS: While some data support benefits in the use of steroids on spinal cord pathology, extensive research suggests at best limited effects and an unresolvable risk/benefit problem. CONCLUSIONS: At present, evidence regarding use of dexamethasone for MSCC is contentious, especially regarding dose regiments. Ultimately, further investigation into the use of steroids is required to determine its utility in treating patients with spinal cord pathology.