The Cost of Postoperative Pancreatic Fistula Versus the Cost of Pasireotide: Results from a Prospective Randomized Trial.

OBJECTIVE: The objective of this study was to determine the costs of clinically significant postoperative pancreatic fistula (POPF) and to evaluate the cost-effectiveness of routine pasireotide use. SUMMARY OF BACKGROUND DATA: We recently completed a prospective randomized trial that demonstrated an 11.7% absolute risk reduction of clinically significant POPF with use of perioperative pasireotide in patients undergoing pancreaticoduodenectomy or distal pancreatectomy [POPF: pasireotide (n = 152), 9% vs placebo (n = 148), 21%; P = 0.006]. METHODS: An institutional modeling system was utilized to obtain total direct cost estimates from the 300 patients included in the trial. This system identified direct costs of hospitalization, physician fees, laboratory tests, invasive procedures, outpatient encounters, and readmissions. Total direct costs were calculated from the index admission to 90 days after resection. Costs were converted to Medicare proportional dollars (MP$). RESULTS: Clinically significant POPF occurred in 45 of the 300 randomized patients (15%). The mean total cost for all patients was MP$23,400 (MP$8,000 - MP$202,500). The mean cost for those who developed clinically significant POPF was MP$39,700 (MP$13,800 - MP$202,500) versus MP$20,500 (MP$8,000 - MP$62,900) for those who did not (P = 0.001). The mean cost of pasireotide within the treatment group (n = 152) was MP$3,300 (MP$300 - MP$3,800). The mean cost was lower in the pasireotide (n = 152) group than the placebo (n = 148) group; however, this did not reach statistical significance (pasireotide, MP$22,800 vs placebo, MP$23,900: P = 0.571). CONCLUSIONS: The development of POPF nearly doubled the total cost of pancreatic resection. In this randomized trial, the routine use of pasireotide significantly reduced the occurrence of POPF without increasing the overall cost of care.

Intralesional laser therapy for vascular malformations.

Intralesional laser therapy for the treatment of vascular malformations (VMs) has been previously reported for select patient populations. Larger studies, over a wider variety of indications, are needed to better define the potential role of this technology. In the current study, a 12-year, retrospective review of 44 patients who underwent 73 intralesional Nd:YAG or diode laser treatments of VMs was performed. The most commonly encountered lesions were venous malformations (66%) and the most commonly involved anatomic locations were the head and neck regions (41%) and lower extremity (39%). Primary indications for treatment were enlargement (73%) and pain (52%). Lesion size was reduced in 94% of cases after treatment and pain was improved in 91% of cases. Minor postoperative complications occurred in 16 (36%) patients. There was no difference in treatment response among various VM subtypes or anatomic locations (P=0.497, P=0.866) or in the incidence of complications (P=0.531, P=0.348). Age was the only factor associated with an increased risk of complications (odds ratio, 1.034; P=0.038). When used in accordance with the suggested guidelines, intralesional laser therapy is a safe and effective treatment modality for VMs of varying compositions and locations.

Outlier kinase expression by RNA sequencing as targets for precision therapy.

Protein kinases represent the most effective class of therapeutic targets in cancer; therefore, determination of kinase aberrations is a major focus of cancer genomic studies. Here, we analyzed transcriptome sequencing data from a compendium of 482 cancer and benign samples from 25 different tissue types, and defined distinct "outlier kinases" in individual breast and pancreatic cancer samples, based on highest levels of absolute and differential expression. Frequent outlier kinases in breast cancer included therapeutic targets like ERBB2 and FGFR4, distinct from MET, AKT2, and PLK2 in pancreatic cancer. Outlier kinases imparted sample-specific dependencies in various cell lines, as tested by siRNA knockdown and/or pharmacologic inhibition. Outlier expression of polo-like kinases was observed in a subset of KRAS-dependent pancreatic cancer cell lines, and conferred increased sensitivity to the pan-PLK inhibitor BI-6727. Our results suggest that outlier kinases represent effective precision therapeutic targets that are readily identifiable through RNA sequencing of tumors.