Novel Implications of Exosomes and lncRNAs in the Diagnosis and Treatment of Pancreatic Cancer

Pancreatic cancer remains a leading cause of cancer-related deaths. Most patients are present with advanced stages of the disease at the time of diagnosis; thus, surgery, which is the best curative option for this malignancy, is no longer an effective treatment modality for affected individuals. As a likely source of “liquid biopsies,” exosomes, which are secreted by fusing intracellular multivesicular bodies with cell membranes, have relative stability and composition, allowing them to cover the entire range of cancer-related biomarkers, including cellular proteins, lipids, DNA, RNA, miRNA, and long non-coding RNAs (lncRNAs). To explore the early detection biomarkers of pancreatic cancer and to develop successful therapeutic intervention for this disease, assessing the implications of exosomes in pancreatic cancer patients is essential. In this chapter, we wish to focus on the possibility of using exosomes and lncRNAs in the clinical management of patients with pancreatic cancer. We will discuss the mechanisms of tumor formation under the exosomal action, demonstrate how circulating exosomes and lncRNAs have come into the research spotlight as likely biomarkers of pancreatic cancer, and discuss the applications of exosomes as transfer vectors in tumor therapeutics

A modified clinically relevant post-operative pancreatic fistula risk evaluation model based on ultrasound shear wave elastography: a prospective study

Objective·To modify previous clinically relevant post-operative pancreatic fistula (CR-POPF) risk evaluation models with quantitative evaluation of pancreatic tissue stiffness by ultrasound shear wave elastography (SWE).Methods·In this prospective study, the patients who were diagnosed as having pancreatic tumors and scheduled to undergo pancreatectomy at Zhongshan Hospital, Fudan University were initially enrolled, whose clinical information was collected. Virtual touch tissue imaging and quantification technology (VTIQ) assessment was applied to the patients within one week before the surgery to measure the shear wave velocity (SWV) of pancreatic lesions and the normal parenchyma of pancreatic body in the superficial layer of the portal vein. During the surgery, the surgeons qualitatively evaluated the stiffness of pancreases via direct palpation and divided them into soft pancreases and medium-hard pancreases. During the 3-week follow-up period after pancreatectomy, CR-POPF was diagnosed according to 2016 International Study Group of Pancreatic Fistula (ISGPF) standard. Peri-operative risk factors of CR-POPF were analyzed by univariate and multivariate Logistic regression to build the prediction model. Evaluation and comparison of diagnostic efficacy and clinical benefits among different models were then performed via receiver operating characteristic (ROC) curve and decision curve analysis (DCA).Results·From September 2021 to March 2022, 100 patients were enrolled in this study, including 33 patients (33.0%) who received pancreaticoduodenectomy (PD) and 67 patients (67.0%) who received distal pancreatectomy. CR-POPF was diagnosed in 35 patients (35.0%) during the 3-week post-pancreatectomy follow-up. Multivariate Logistic regression analysis revealed that the SWV value of the body part of pancreatic parenchyma in the superficial layer of the portal vein [lgOR=-2.934 (95%CI -4.387‒-1.479), P=0.000] and the presence of a non-dilated main pancreatic duct (≤3 mm) [lgOR=0.805 (95%CI 0.274‒1.335), P=0.003] were independent risk factors that significantly correlated with the occurrence of CR-POPF after pancreatectomy. The modified model based on the SWE parameter achieved the area under the ROC curve of 0.842, with the sensitivity, the specificity, the positive predictive value, the negative predictive value and the likelihood ratio of 85.7%, 64.6%, 70.5%, 81.8% and 2.422 in predicting CR-POPF. DCA revealed a better clinical benefit of the modified model compared to the previous prediction models [fistula risk score (FRS) and alternative fistula risk score (a-FRS)].Conclusion·The modified model based on the SWE parameter and identified clinical risk factors can make non-invasive, quantitative and objective evaluation of CR-POPF risk before pancreatectomy, and provide sufficient diagnostic efficacy and clinical benefits

Should Steroid Therapy Be Necessarily Needed for Autoimmune Pancreatitis Patients with Lesion Resected due to Misdiagnosed or Suspected Malignancy?

To explore whether steroid therapy should be needed for autoimmune pancreatitis patients after operation, eight AIP patients receiving operation were enrolled in this study from January 2007 to July 2013. All patients underwent liver function, CA19-9, and contrast-enhanced CT and/or MRI. Tests of IgG and IgG4 were performed in some patients. Tests of serum TB/DB, γ-GT, and γ-globulin were undergone during the perioperative period. Six cases receiving resection were pathologically confirmed as AIP patients and two were confirmed by intraoperative biopsy. For seven patients, TB/DB level was transiently elevated 1 day or 4 days after operation but dropped below preoperative levels or to normal levels 7 days after operation, and serum γ-GT level presented a downward trend. Serum γ-globulin level exhibited a downward trend among six AIP patients after resection, while an upward trend was found in another two AIP patients receiving internal drainage. Steroid therapy was not given to all six AIP patients until two of them showed new lines of evidence of residual or extrapancreatic AIP lesion after operation, while another two cases without resection received steroid medication. Steroid therapy might not be recommended unless there are new lines of evidence of residual extrapancreatic AIP lesions after resection

Induction of protective and therapeutic anti-pancreatic cancer immunity using a reconstructed MUC1 DNA vaccine

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is a common, highly lethal disease with a rising incidence. MUC1 is a tumor-associated antigen that is over-expressed in pancreatic adenocarcinoma. Active immunotherapy that targets MUC1 could have great treatment value. Here we investigated the preventive and therapeutic effect of a MUC1 DNA vaccine on the pancreatic cancer.</p> <p>Methods</p> <p>MUC1-various tandem repeat units(VNTR) DNA vaccine was produced by cloning one repeat of VNTR and inserting the cloned gene into the pcDNA3.1. In the preventive group, female C57BL/6 mice were immunized with the vaccine, pcDNA3.1 or PBS; and challenged with panc02-MUC1 or panc02 cell. In the therapeutic group the mice were challenged with panc02-MUC1 or panc02 cell, and then immunized with the vaccine, pcDNA3.1 or PBS. The tumor size and the survival time of the animals were compared between these groups.</p> <p>Results</p> <p>The DNA vaccine pcDNA3.1-VNTR could raise cytotoxic T lymphocyte (CTL) activity specific for MUC1. In the preventive experiment, the mice survival time was significantly longer in the vaccine group than in the control groups (<it>P </it>< 0.05). In the therapeutic experiment, the DNA vaccine prolonged the survival time of the panc02-MUC1-bearing mice (<it>P </it>< 0.05). In both the preventive and therapeutic experiments, the tumor size was significantly less in the vaccine group than in the control groups (<it>P </it>< 0.05). This pcDNA3.1-VNTR vaccine, however, could not prevent the mice attacked by panc02 cells and had no therapeutic effect on the mice attacked by panc02 cells.</p> <p>Conclusion</p> <p>The MUC1 DNA vaccine pcDNA3.1-VNTR could induce a significant MUC1-specific CTL response; and had both prophylactic and therapeutic effect on panc02-MUC1 tumors. This vaccine might be used as a new adjuvant strategy against pancreatic cancer.</p

Proteomics analysis of serum protein profiling in pancreatic cancer patients by DIGE: up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer has significant morbidity and mortality worldwide. Good prognosis relies on an early diagnosis. The purpose of this study was to develop techniques for identifying cancer biomarkers in the serum of patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples from five individuals with pancreatic cancer and five individuals without cancer were compared. Highly abundant serum proteins were depleted by immuno-affinity column. Differential protein analysis was performed using 2-dimensional differential in-gel electrophoresis (2D-DIGE).</p> <p>Results</p> <p>Among these protein spots, we found that 16 protein spots were differently expressed between the two mixtures; 8 of these were up-regulated and 8 were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of mannose-binding lectin 2 and myosin light chain kinase 2, which have not previously been implicated in pancreatic cancer, were observed. In an independent series of serum samples from 16 patients with pancreatic cancer and 16 non-cancer-bearing controls, increased levels of mannose-binding lectin 2 and myosin light chain kinase 2 were confirmed by western blot.</p> <p>Conclusions</p> <p>These results suggest that affinity column enrichment and DIGE can be used to identify proteins differentially expressed in serum from pancreatic cancer patients. These two proteins 'mannose-binding lectin 2 and myosin light chain kinase 2' might be potential biomarkers for the diagnosis of the pancreatic cancer.</p

Timing of surgery following SARS-CoV-2 infection: an international prospective cohort study.

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay