Controlling Nutritional Status score is superior to Prognostic Nutritional Index score in predicting survival and complications in pancreatic ductal adenocarcinoma: a Chinese propensity score matching study.

Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients' nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.

Enrichment of extracellular vesicles with lipid nanoprobe functionalized nanostructured silica.

Nanoscale extracellular vesicles (nEVs) have recently demonstrated potential value in cancer diagnostics and treatment monitoring, but translation has been limited by technical challenges in nEV isolation. Thus, we have developed a one-step nEV isolation platform that utilizes nEV size-matched silica nanostructures and a surface-conjugated lipid nanoprobe with an integrated microfluidic mixer. The reported platform has 28.8% capture efficiency from pancreatic cancer plasma and can sufficiently enrich nEVs for simpler positive identification of point mutations, particularly KRAS, in nEV DNA from the plasma of pancreatic cancer patients.

Size-based separation methods of circulating tumor cells.

Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. Compared to other "liquid biopsy" portfolios such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable advantages in analyses of transcriptomics, proteomics, and signal colocalization. Hence, CTCs hold the key to understanding the biology of metastasis and play a vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based enrichment features are prominent in CTC isolation. It is a label-free, simple and fast method. Enriched CTCs remain unmodified and viable for a wide range of subsequent analyses. In this review, we comprehensively summarize the differences of size and deformability between CTCs and blood cells, which would facilitate the development of technologies of size-based CTC isolation. Then we review representative size-/deformability-based technologies available for CTC isolation and highlight the recent achievements in molecular analysis of isolated CTCs. To wrap up, we discuss the substantial challenges facing the field, and elaborate on prospects.

In Situ Caging of Biomolecules in Graphene Hybrids for Light Modulated Bioactivity.

Remote and noninvasive modulation of protein activity is essential for applications in biotechnology and medicine. Optical control has emerged as the most attractive approach owing to its high spatial and temporal resolutions; however, it is challenging to engineer light responsive proteins. In this work, a near-infrared (NIR) light-responsive graphene-silica-trypsin (GST) nanoreactor is developed for modulating the bioactivity of trypsin molecules. Biomolecules are spatially confined and protected in the rationally designed compartment architecture, which not only reduces the possible interference but also boosts the bioreaction efficiency. Upon NIR irradiation, the photothermal effect of the GST nanoreactor enables the ultrafast in situ heating for remote activation and tuning of the bioactivity. We apply the GST nanoreactor for remote and ultrafast proteolysis of proteins, which remarkably enhances the proteolysis efficiency and reduces the bioreaction time from the overnight of using free trypsin to seconds. We envision that this work not only provides a promising tool of ultrafast and remotely controllable proteolysis for in vivo proteomics in study of tissue microenvironment and other biomedical applications but also paves the way for exploring smart artificial nanoreactors in biomolecular modulation to gain insight in dynamic biological transformation.

Novel and supplementary management of pancreatic fluid collections: Endoscopic ultrasound-guided drainage.

AIM: To compare efficacy and safety of endoscopic ultrasound (EUS)-guided and surgical drainage in pancreatic fluid collection management. METHODS: Data were obtained retrospectively from January 2012 to December 2016. Patients with pancreatic fluid collection were performed EUS-guided or surgical procedure. Main outcome measures including clinical efficiency, complication, duration of procedures, hospital stay and cost were analyzed. RESULTS: Thirty-six patients were enrolled into the study, including 14 in endoscopic group while 22 in the surgical group. Twelve (86%) patients were treated successfully by endoscopic approach while 21 (95%) patients benefited through surgical procedure. Endoscopic treatment had higher recurrence and complication rates than surgery, resulting in more re-interventions. Meanwhile, duration of procedure, hospital stay and cost were significantly lower in endoscopic group. CONCLUSION: Both approaches were effective and safe. EUS-guided approach should be the first-line treatment in mild and simple cases, while surgical approach should be considered as priority in severe and complex cases.

Rapid magnetic isolation of extracellular vesicles via lipid-based nanoprobes.

Extracellular vesicles (EVs) can mediate intercellular communication by transferring cargo proteins and nucleic acids between cells. The pathophysiological roles and clinical value of EVs are under intense investigation, yet most studies are limited by technical challenges in the isolation of nanoscale EVs (nEVs). Here, we report a lipid nanoprobe that enables spontaneous labelling and magnetic enrichment of nEVs in 15 minutes, with isolation efficiency and cargo composition similar to what can be achieved by the much slower and bulkier method of ultracentrifugation. We also show that the lipid nanoprobes, which allow for downstream analyses of nucleic acids and proteins, enabled the identification of EGFR and KRAS mutations following nEV isolation from blood plasma from non-small-cell lung-cancer patients. The efficiency and versatility of the lipid nanoprobe opens up opportunities in point-of-care cancer diagnostics.

Accuracy of routine multidetector computed tomography to identify arterial variants in patients scheduled for pancreaticoduodenectomy.

AIM: To assess the efficacy of cross-sectional multidetector computed tomography (MDCT) imaging without arterial reconstruction to identify aberrant right hepatic artery (RHA) and celiac artery stenosis (CAS) in patients scheduled for pancreaticoduodenectomy. METHODS: Patients with peri-ampullary and pancreatic head tumors who underwent routine preoperative MDCT and subsequent computed tomography (CT) angiography (CTA), conventional angiography or pancreaticoduodenectomy between September 2007 and August 2013 were identified. Retrospective analysis of imaging data was undertaken using CTA, conventional angiographic and surgical findings as the reference standards. The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MDCT in evaluation of aberrant RHA and CAS were calculated. RESULTS: A group of 458 patients met the inclusion criteria of this study to detect aberrant RHA, and 181 cases were included to identify CAS. Fifty-four (11.8%) patients were confirmed to have aberrant RHA, while 12 (6.6%) patients with CAS were demonstrated. MDCT yielded an accuracy of 98.5%, sensitivity of 96.3% and specificity of 98.8% in the detection of aberrant RHA. The sensitivity, specificity, PPV and NPV of MDCT for detecting CAS were 58.3%, 98.2%, 70% and 97.1%, respectively. CONCLUSION: Routine MDCT is recommended such that surgeons and radiologists be alerted to the importance of arterial variants on preoperative CT scans in patients scheduled for pancreaticoduodenectomy.

Nanostructured microfluidic digestion system for rapid high-performance proteolysis.

A novel microfluidic protein digestion system with a nanostructured and bioactive inner surface was constructed by an easy biomimetic self-assembly strategy for rapid and effective proteolysis in 2 minutes, which is faster than the conventional overnight digestion methods. It is expected that this work would contribute to rapid online digestion in future high-throughput proteomics.

MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1.

miRNA-218 is a highlighted tumor suppressor and its underlying role in tumor progression is still unknown. Here, we restored the expression of miRNA-218 in pancreatic cancer to clarify the function and potent downstream pathway of miRNA-218. The expressions of both miRNA-218 and its potent target gene ROBO1 were revealed by RT-PCR and western blotting analysis. Transfection of miRNA-218 precursor mimics and luciferase assay were performed to elucidate the regulation mechanism between miRNA-218 and ROBO1. Cells, stably expressing miRNA-218 followed by forced expression of mutant ROBO1, were established through co-transfections of both lentivirus vector and plasmid vector. The cell migration and invasion abilities were evaluated by migration assay and invasion assay respectively. An increased expression of ROBO1 was revealed in cell BxPC-3-LN compared with cell BxPC-3. Elevated expression of miRNA-218 would suppress the expression of ROBO1 via complementary binding to a specific region within 3'UTR of ROBO1 mRNA (sites 971-978) in pancreatic cancer cells. Stably restoring the expression of miRNA-218 in pancreatic cancer significantly downregulated the expression of ROBO1 and effectively inhibited cell migration and invasion. Forced expression of mutant ROBO1 could reverse the repression effects of miRNA-218 on cell migration and invasion. Consequently, miRNA-218 acted as a tumor suppressor in pancreatic cancer by inhibiting cell invasion and migration. ROBO1 was a functional target of miRNA-218's downstream pathway involving in cell invasion and migration of pancreatic cancer.

64-slice CT perfusion imaging of pancreatic adenocarcinoma and mass-forming chronic pancreatitis.

RATIONALE AND OBJECTIVES: To investigate 64 computed tomography (CT) perfusion imaging features of patients with pancreatic cancer and mass-forming chronic pancreatitis. MATERIALS AND METHODS: Between January 2003 and April 2010, 234 patients with pancreatic mass underwent 64-CT perfusion imaging. Among them, the histopathological results of 64 patients were proven to be pancreatic adenocarcinoma and 15 patients were proven to be mass-forming chronic pancreatitis. Additionally, CT perfusion imaging was performed in 33 healthy volunteers served as controls. The slice data were processed using CT perfusion software. Perfusion parameters including time density curve, blood flow, blood volume, permeability, peak enhancement, and time to peak were recorded. RESULTS: Blood flow was 77% lower in patients with pancreatic adenocarcinoma than in controls, 48% lower in patients with mass-forming chronic pancreatitis than in controls, and 56% lower in patients with pancreatic adenocarcinoma than with mass-forming chronic pancreatitis (P < .016). Blood volume was 65% lower in pancreatic adenocarcinoma than in controls, 27% lower in mass-forming chronic pancreatitis than in controls, and 53% lower in cancer than mass-forming chronic pancreatitis (P < .016). Permeability was 559% higher in pancreatic adenocarcinoma than in controls, 821% higher in mass-forming chronic pancreatitis than in controls, and 28% lower in cancer than mass-forming chronic pancreatitis (P < .016). Peak enhancement was 27% lower and time to peak 23% longer in pancreatic adenocarcinoma than mass-forming chronic pancreatitis (P < .016). Time-density curve showed the peak of mass-forming chronic pancreatitis is earlier and higher than that of pancreatic adenocarcinoma, and the peak of mass-forming chronic pancreatitis is later and lower than that of controls. CONCLUSION: CT perfusion imaging can provide additional quantitative hemodynamic information of pancreatic adenocarcinoma and mass-forming chronic pancreatitis.