Pain control with continuous infusion preperitoneal wound catheters versus continuous epidural analgesia in colon and rectal surgery: A randomized controlled trial.

OBJECTIVE: To compare continuous infusion preperitoneal wound catheters (CPA) versus continuous epidural analgesia (CEA) after elective colorectal surgery. METHODS: An open-label equivalence trial randomizing patients to CPA or CEA. Primary outcomes were postoperative pain as determined by numeric pain scores and supplemental narcotic analgesia requirements. Secondary outcomes included incidence of complications and patient health status measured with the SF-36 Health Survey (Acute Form). RESULTS: 98 patients were randomized [CPA (N = 50, 51.0%); CEA (N = 48, 49.0%)]. 90 patients were included [ CPA 46 (51.1%); CEA 44 (48.9%)]. Pain scores were significantly higher in the CPA group in the PACU (p = 0.04) and on the day of surgery (p < 0.01) as well as supplemental narcotic requirements on POD 0 (p = 0.02). No significant differences were noted in postoperative complications between groups, aggregate SF-36 scores and SF-36 subscale scores. CONCLUSIONS: Continuous epidural analgesia provided superior pain control following colorectal surgery in the PACU and on the day of surgery. The secondary endpoints of return of bowel function, length of stay, and adjusted SF-36 were not affected by choice of peri-operative pain control.

Whole Genome Sequencing of Newly Established Pancreatic Cancer Lines Identifies Novel Somatic Mutation (c.2587G>A) in Axon Guidance Receptor Plexin A1 as Enhancer of Proliferation and Invasion.

The genetic profile of human pancreatic cancers harbors considerable heterogeneity, which suggests a possible explanation for the pronounced inefficacy of single therapies in this disease. This observation has led to a belief that custom therapies based on individual tumor profiles are necessary to more effectively treat pancreatic cancer. It has recently been discovered that axon guidance genes are affected by somatic structural variants in up to 25% of human pancreatic cancers. Thus far, however, some of these mutations have only been correlated to survival probability and no function has been assigned to these observed axon guidance gene mutations in pancreatic cancer. In this study we established three novel pancreatic cancer cell lines and performed whole genome sequencing to discover novel mutations in axon guidance genes that may contribute to the cancer phenotype of these cells. We discovered, among other novel somatic variants in axon guidance pathway genes, a novel mutation in the PLXNA1 receptor (c.2587G>A) in newly established cell line SB.06 that mediates oncogenic cues of increased invasion and proliferation in SB.06 cells and increased invasion in 293T cells upon stimulation with the receptor's natural ligand semaphorin 3A compared to wild type PLXNA1 cells. Mutant PLXNA1 signaling was associated with increased Rho-GTPase and p42/p44 MAPK signaling activity and cytoskeletal expansion, but not changes in E-cadherin, vimentin, or metalloproteinase 9 expression levels. Pharmacologic inhibition of the Rho-GTPase family member CDC42 selectively abrogated PLXNA1 c.2587G>A-mediated increased invasion. These findings provide in-vitro confirmation that somatic mutations in axon guidance genes can provide oncogenic gain-of-function signals and may contribute to pancreatic cancer progression.