Comparison of Uncinate Process Cancer and Non-Uncinate Process Pancreatic Head Cancer

The special anatomical position accounts for unusual clinicopathological features of uncinate process cancer. This study aimed to compare clinicopathological features of patients with uncinate process cancer to patients with non-uncinate process pancreatic head cancer. Total 160 patients with pancreatic head cancer were enrolled and classified into two groups: uncinate process cancer and non-uncinate process pancreatic head cancer. We found that the ratio of vascular invasion was significantly higher in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In addition, the rate of R1 resection was significantly higher in patients with uncinate process cancer. Furthermore, the median disease-free survival (11 months vs. 15 months, p= 0.043) and overall survival (15 months vs. 19 months, p= 0.036) after R0 resection were lower for uncinate process cancer. Locoregional recurrence was more frequent (p= 0.017) and earlier (12 months vs. 36 months; p= 0.002) in patients with uncinate process cancer than in patients with non-uncinate process pancreatic head cancer. In conclusion, uncinate process cancer is more likely to invade blood vessel and has worse prognosis due to the earlier and more frequent locoregional recurrence.Beijing Municipal Science & Technology Commission [Z131107002213043, Z161100000516038]SCI(E)[email protected]

Stem cell-like circulating tumor cells identified by Pep@MNP and their clinical significance in pancreatic cancer metastasis

ObjectiveThe circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.MethodsCTCs were captured by Pep@MNP. CTCs were identified via immunofluorescence with CD45, cytokeratin antibodies, and the CXCR4 positive CTCs were assigned to be HM-CTCs.ResultsThe over-expression of CXCR4 could promote the migration of pancreatic cancer cell in vitro and in vivo. In peripheral blood (PB), CTCs were detected positive in 79.0% of all patients (49/62, 9 (0–71)/2mL), among which 63.3% patients (31/49, 3 (0–23)/2mL) were HM-CTCs positive. In portal vein blood (PVB), CTCs were positive in 77.5% of patients (31/40, 10 (0–40)/2mL), and 67.7% of which (21/31, 4 (0–15)/2mL) were HM-CTCs positive CTCs enumeration could be used as diagnostic biomarker of pancreatic cancer (AUC = 0.862), and the combination of CTCs positive and CA19–9 increase shows improved diagnostic accuracy (AUC = 0.963). in addition, PVB HM-CTCs were more accurate to predict the early recurrence and liver metastasis than PB HM-CTCs (AUC 0.825 vs. 0.787 and 0.827 vs. 0.809, respectively).ConclusionsThe CTCs identified by Pep@MNP detection system could be used as diagnostic and prognostic biomarkers of PDAC patients. We identified and defined the CXCR4 over-expressed CTC subpopulation as highly metastatic-prone CTCs, which was proved to identify patients who were prone to suffering from early recurrence and metastasis

International expert consensus on laparoscopic pancreaticoduodenectomy

Importance: While laparoscopic pancreaticoduodenectomy (LPD) is being adopted with increasing enthusiasm worldwide, it is still challenging for both technical and anatomical reasons. Currently, there is no consensus on the technical standards for LPD.Objective: The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review: An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy. Statements were produced upon reviewing the literature and assessed by the members of the expert panel. The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019. The Web of Science, Medline, and Cochrane Library and Clinical Trials databases were searched, The search strategy included, but was not limited to, the terms 'laparoscopic', 'pancreaticoduodenectomy, 'pancreatoduodenectomy', 'Whipple's operation', and 'minimally invasive surgery'. Reference lists from the included articles were manually checked for any additional studies, which were included when appropriate. Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements. The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan, China.Findings: Twenty-eight international experts from 8 countries constructed the expert panel. Sixteen statements were produced by the members of the expert panel. At least 80% of responders agreed with the majority (80%) of statements. Other than three randomized controlled trials published to date, most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance: The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD. LPD is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.</p

Circulating cell-free DNA methylation analysis of pancreatic cancer patients for early noninvasive diagnosis

BackgroundAberrant hypermethylation of genomic DNA CpG islands (CGIs) is frequently observed in human pancreatic cancer (PAC). A plasma cell-free DNA (cfDNA) methylation analysis method can be utilized for the early and noninvasive detection of PAC. This study also aimed to differentiate PAC from other cancer types.MethodsWe employed the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, which targets approximately one-third of CGIs, on plasma samples from PAC patients (n = 50) and healthy controls (n = 52), as well as from cancerous and adjacent noncancerous tissue samples (n = 66). The method’s efficacy in detecting PAC and distinguishing it from hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC) was evaluated. Additionally, a methylation score and typing system for PAC was also established.ResultsWe identified a total of 120 cfDNA methylation biomarkers, including IRX4, KCNS2, and RIMS4, for the detection of PAC in blood. A panel comprising these biomarkers achieved a sensitivity of 97% and 86% for patients in the discovery and validation cohorts, respectively, with a specificity of 100% in both cohorts. The methylation scoring and typing systems were clinically applicable. Furthermore, we identified hundreds of differentially methylated cfDNA biomarkers between PAC and HCC, CRC, and GC. Certain combinations of these markers can be used in a highly specific (approximately 100%) algorithm to differentiate PAC from HCC, CRC, and GC in blood.ConclusionsOur study identified cfDNA methylation markers for PAC, offering a novel approach for the early, noninvasive diagnosis of PAC

Crosstalk between Pancreatic Cancer Cells and Cancer-Associated Fibroblasts in the Tumor Microenvironment Mediated by Exosomal MicroRNAs

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant digestive tumors, characterized by a low rate of early diagnosis, strong invasiveness, and early metastasis. The abundant stromal cells, dense extracellular matrix, and lack of blood supply in PDAC limit the penetration of chemotherapeutic drugs, resulting in poor efficacy of the current treatment regimens. Cancer-associated fibroblasts (CAFs) are the major stromal cells in the tumor microenvironment. Tumor cells can secrete exosomes to promote the generation of activated CAFs, meanwhile exosomes secreted by CAFs help promote tumor progression. The aberrant expression of miRNAs in exosomes is involved in the interaction between tumor cells and CAFs, which provides the possibility for the application of exosomal miRNAs in the diagnosis and treatment of PDAC. The current article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and CAFs in the tumor microenvironment, in order to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosome miRNA in human PDAC