Metabolites of Purine Nucleoside Phosphorylase (NP) in Serum Have the Potential to Delineate Pancreatic Adenocarcinoma

Pancreatic Adenocarcinoma (PDAC), the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS) and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX). A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7) and Alpha Synuclein (aSyn), both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP) which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC

Robotic Inguinal Hernia Repair Outcomes: Operative Time and Cost Analysis.

BACKGROUND: Robotic inguinal hernia repair is the latest iteration of minimally invasive herniorrhaphy. Previous studies have shown expedited learning curves compared to traditional laparoscopy, which may be offset by higher cost and longer operative time. We sought to compare operative time and direct cost across the evolving surgical practice of 10 surgeons in our healthcare system. METHODS: This is a retrospective review of all transabdominal preperitoneal robotic inguinal hernia repairs performed by 10 general surgeons from July 2015 to September 2018. Patients requiring conversion to an open procedure or undergoing simultaneous procedures were excluded. The data was divided to compare each surgeon\u27s initial 20 cases to their subsequent cases. Direct operative cost was calculated based on the sum of supplies used intra-operatively. Multivariate analysis, using a generalized estimating equation, was adjusted for laterality and resident involvement to evaluate outcomes. RESULTS: Robotic inguinal hernia repairs were divided into two groups: early experience (n = 167) and late experience (n = 262). The late experience had a shorter mean operative time by 17.6 min (confidence interval: 4.06 - 31.13, p = 0.011), a lower mean direct operative cost by $538.17 (confidence interval: 307.14 - 769.20, p \u3c 0.0001), and fewer postoperative complications (p = 0.030) on multivariate analysis. Thirty-day readmission rates were similar between both groups. CONCLUSION: Increasing surgeon experience with robotic inguinal hernia repair is associated with a predictable reduction in operative time, complication rates, and direct operative cost per case. Thirty-day readmission rates are not affected by the learning curve