ObjectiveTo explore feasibility of mRNA vaccines as a novel strategy for individualized precision treatment of pancreatic cancer (PC). MethodThe recent domestic and international literature on vaccine research in PC was reviewed. ResultsThe heterogeneity between and within the pancreatic tumors had limited the efficacy of traditional vaccines based on cells, exosomes, proteins, peptides, or DNA for PC. The mRNA vaccine was considered as a promising alternative therapy due to its precise targeting, low toxicity, and ability to induce long-lasting immune memory. Breakthroughs in the tumor antigen recognition, immune subtype differentiation, and mRNA vaccine construction, the development strategy of PC mRNA vaccine would further facilitate the development of personalized precision medicine. The existing mRNA vaccines usually need to be combined with other immunotherapy methods to improve efficacy, while the development of preventive vaccines is still exploraing. ConclusionsmRNA vaccines, as an innovative and promising platform, offer a new hope for the development of PC vaccines. However, the heterogeneity of PC has resulted in poor efficacy with traditional vaccines. Although the limitations of traditional vaccines and the heterogeneity of PC itself, the more challenges of vaccine research of PC is facing, the advantages of mRNA vaccine still make it possible to treat PC. In the face of the challenge of complex characteristics of PC, more research is needed to support the transformation and application of mRNA vaccine in clinical therapy.
ObjectivesTo evaluate the economic efficacy of nab-paclitaxel (NAB-P) combined with gemcitabine (GEM) versus GEM alone in the treatment of metastatic pancreatic cancer in China.MethodsA Markov model simulating the costs and health outcomes was developed to estimate quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). The impact of parameter uncertainty on the model was assessed by deterministic one-way sensitivity analysis.ResultsNAB-P combined with GEM was shown superior efficacy compared to gemcitabine monotherapy, however with higher costs. The ICER between the two groups was 964 780.79￥/QALY.ConclusionsCompared with gemcitabine monotherapy, NAB-P combined with GEM is not cost-effective. The conclusion is confirmed by deterministic one-way sensitivity analysis.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
Objective To investigate safety and therapeutic effect of total pancreatectomy plus splenectomy for patient with pancreatic cancer. Methods The preoperative clinical data, surgical treatment, and postoperative conditions of 1 patient with pancreatic cancer who underwent the total pancreatectomy plus splenectomy in the Affiliated Hospital of Qinghai University in January 2018 were retrospectively analyzed. Results Combination of the patient clinical history, physical examination, laboratory and radiologic results, the patient was diagnosed with the pancreatic cancer. Then the patient underwent the Whipple procedure. During the operation, it was found that the texture of the pancreas was hard, and the spleen arteriovenous were considered to be invaded, and the multiple frozen section analysis during the operation showed that the surgical margin was positive. Eventually, the total pancreatectomy plus splenectomy was performed. The postoperative pathological analysis results revealed to the well-moderately differentiated tubular adenocarcinoma. When the condition of patient became stable, the pancreatin and insulin were required for long time. No severe complications occurred. The patient survived well after the surgery and no recurrence was observed for following-up of 3 months. Conclusion With improvement of surgical techniques and enhancement of postoperative management, total pancreatectomy can be used as a treatment for pancreatic cancer and it is still safe and feasible.
ObjectiveTo further evaluate the relation between usage of proton pump inhibitor (PPI) and the risk of pancreatic cancer. MethodThe observational studies were systematically searched in the databases of PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, and VIP. The combined odds ratio (OR) and 95% confidence interval (CI) of pancreatic cancer risk were estimated by the corresponding effect model according to the heterogeneous results, and the subgroup analysis, meta-regression, and sensitivity analysis were performed. In addition, the relation between the defined daily dose (DDD) and usage time of PPI and the pancreatic cancer risk were studied by using restricted cubic spline. ResultsA total of 14 studies were included, including 1 601 430 subjects. The meta-analysis result showed that usage of PPI was positively correlated with the risk of pancreatic cancer [I2=98.9%, OR (95%CI)=1.60 (1.21, 2.11), P<0.001]. The subgroup analysis results showed that usage of PPI would increase the risk of pancreatic cancer in the subgroups of literature published before 2018 [OR (95%CI)=1.88 (1.05, 3.38), P=0.034], non-Asian regions [OR (95%CI)=1.37 (1.04, 1.82), P=0.028], case-control studies [OR (95%CI)=1.59 (1.16, 2.18), P=0.004], cohort studies [OR (95%CI)=1.65 (1.13, 2.39), P=0.009], and high-quality studies [OR (95%CI)=1.62 (1.19, 2.20), P=0.002]. The dose-response curve showed that there was a nonlinear relation between the usage of PPI and the risk of pancreatic cancer (χ2linear=2.27, P=0.132; Pnonlinear=0.039). When the usage of PPI was 800 DDD or less, usage of PPI would increase the risk of pancreatic cancer, but there was no statistical significance when the usage of PPI was more than 800 DDD. The time-effect curve showed that there was a linear relation between the usage time of PPI and the risk of pancreatic cancer (χ2linear=6.92, P=0.009), and the risk of pancreatic cancer would increase by 2.3% if the usage of PPI increased by one month [OR=1.02, 95%CI (1.01, 1.04), P=0.009]. The sensitivity analysis confirmed that the results were stable by gradually eliminating each study, the OR (95%CI) of the risk of pancreatic cancer was 1.37 (1.08, 1.74) to 1.66 (1.22, 2.27), and the publication bias was not found by Egger test (P=0.594).ConclusionsFrom the results of this meta-analysis, usage of PPI will increase the risk of pancreatic cancer, and the dosage of PPI and usage time of PPI may be related to the risk of pancreatic cancer. The clinical usage of PPI should be strictly controlled, and the dosage and usage time should also be carefully considered.
ObjectiveTo summarize the current treatment status and progress of neoadjuvant chemotherapy for pancreatic cancer in order to improve the understanding of neoadjuvant chemotherapy and to guide clinical work.MethodThe relevant literatures at home and abroad on neoadjuvant chemotherapy for pancreatic cancer were readed and reviewed.ResultsNeoadjuvant chemotherapy could reduce tumor lesions, increase R0 resection rate, decrease postoperative complication rate, and improve patients’ survival, however, there was currently no high quality evidence-based medicine proof. At present, there was no unified neoadjuvant chemotherapy regimens for pancreatic cancer in the world. FOLFIRINOX, gemcitabine plus S-1, and gencitabine plus Nab-paclitaxel were the three common regimens we used. In addition, the neoadjuvant chemotherapy of pancreatic cancer had no uniform standard, and there were insufficient methods for evaluating therapeutic effects.ConclusionAlthough there are still some core problems need to be solved in neoadjuvant chemotherapy for pancreatic cancer, however, it’s curative effect is gradually recognized and widely used by clinicians, which is beneficial to provide a better prognosis for pancreatic cancer patients.
ObjectiveTo summarize the recent advances in the pathogenic mechanism of microorganisms and pancreatic cancer.MethodThrough the retrieval of relevant literatures, the recent progresses in the study of microorganism and pathogenesis of pancreatic cancer were reviewed.ResultsIn recent years, the potential role of intestinal microbiota in the pathogenic mechanism of pancreatic cancer had been studied. The studies found that the microbiome played an important role in the development of pancreatic cancer. Among them, the infections of Helicobacter pylori, oral pathogenic bacteria such as the Porphyromonas ginggivalis, Aggregatibacter actinomycetemcomitans and Phylum fusobacteria, and the changes of composition and diversity of intestinal microflora were closely related to the pancreatic cancer. The microorganisms induced the chronic inflammation and immune response through multiple pathways. The bacterial lipopolysaccharide stimulated the mutations in the KARS gene and mediated the inflammatory response by activating the nuclear factor-κB signaling pathway through Toll like receptor. The oral pathogenic microorganisms and Helicobacter pylori could also promote the cancer progression by secreting toxins that activated cancer-related signaling pathways.ConclusionsBacteria might be important carcinogens. These microorganisms promote development of cancer by causing chronic inflammation, activating cancer-related pathways, activating immune response, oxidative stress, and damaging DNA double strands.
ObjectiveTo analyze the R0 resection rate and survival time of pancreatic cancer with serum IgG4 elevated, and to discuss whether serum IgG4 can distinguish autoimmune pancreatitis from pancreatic cancer.MethodsThe retrospective cohort study was adopted. The clinical data of 146 patients with pancreatic cancer confirmed by histology in Affiliated Hospital of Qingdao University from January 2016 to December 2019 were analyzed retrospectively. According to the level of serum IgG4, they were divided into normal IgG4 group (<1.35 g/L, n=124) and IgG4 elevated group (≥1.35 g/L, n=22). The tumor R0 resection rate, survival time and whether complicated with AIP of the two groups were compared.ResultsOne hundred and one patients (81.5%) with normal serum IgG4 underwent radical surgery, while only 13 patients (59.1%) with elevated serum IgG4 underwent radical surgery, the difference was significant (P=0.019). The median survival time of patients with normal serum IgG4 was 18.7 months, while patients with elevated serum IgG4 was 8.1 months, there was no significant difference between the two groups (P=0.121). Subgroup analysis showed that the median survival time of patients with pancreatic ductal adenocarcinoma in the normal IgG4 group was 17.5 months, while the IgG4 elevated group was 6.8 months, the difference was significant (P=0.016). Only 1 case of pancreatic cancer with AIP in the 2 groups.ConclusionsSerum IgG4 ≥1.35 g/L indicates low radical resection rate in pancreatic cancer and poor prognosis in pancreatic ductal adenocarcinoma. Serum IgG4 can only be used as an auxiliary index to distinguish pancreatic cancer from autoimmune pancreatitis.
ObjectiveTo determine the prognostic significance of change of systemic immune inflammation index (SII) before and after neoadjuvant chemotherapy (NCT) in advanced pancreatic cancer.MethodsThe patients with advanced pancreatic cancer who received the NCT before pancreatectomy and met the inclusion and exclusion criteria of this study from January 2013 to December 2016 in the Panjin Liao-Oil Gem Flower Hospital were retrospectively collected. The patients were designed into an increased SII group (SII before NCT was lower than after NCT) and decreased SII group (SII before NCT was higher than after NCT) according to the change of SII before and after NCT. The laboratory data before and after NCT were collected to calculate the SII and to analyze the relationship between the change of SII before and after NCT and the clinical outcomes. The clinicopathologic characteristics and postoperative 3-year survival rate of the two groups were compared. The Cox regression was used to evaluate the influencing factors of postoperative survival of advanced pancreatic cancer.ResultsAll of 103 patients were included, 42 of whom in the increased SII group and 61 in the decreased SII group. The proportions of the intraoperative tumor size >3 cm, CA19-9>37 U/mL after NCT, and postoperative complications in the increased SII group were significantly higher than those in the decreased SII group (P<0.05). All 103 patients were followed up from 9 to 81 months with median 13 months, the 3-year cumulative survival rate of patients in the increased SII group was significantly lower than that of patients in the decreased SII group (19.0% versus 42.6%, P=0.012). The results of the multivariate analysis showed that the CA19-9>37 U/mL after NCT [HR=2.084, 95%CI (1.140, 3.809), P=0.017], postoperative complications [HR=1.657, 95%CI (1.009, 2.722), P=0.046], the absent of postoperative adjuvant chemotherapy [HR=1.795, 95%CI (1.085, 2.970), P=0.023], and the elevated SII after NCT [HR=1.849, 95%CI (1.111, 3.075), P=0.018] were the independent risk factors affecting postoperative 3-year survival rate of patients with advanced pancreatic cancer.ConclusionsThe change value of SII before and after NCT is an independent risk factor for the prognosis of patient with advanced pancreatic cancer, the elevated SII after NCT is a poor prognosis index in patient with advanced pancreatic cancer. However, the evaluations of larger controlled trials are necessary at multiple institutions before introduction of SII as a prognostic indicator in clinical practice.
ObjectiveTo understand the research status and future directions of circular RNA (circRNA) in pancreatic cancer, and to provide references for its further research.MethodThe recent literatures on studies of the role of circRNA in the pancreatic cancer were reviewed.ResultsThe retsults of high-throughput sequencing had shown that large amounts of circRNA expressed abnormally in the pancreatic cancer tissues and pancreatic cancer cell lines, and they participated in the occurrence and development of pancreatic cancer, drug resistance, autophagy, and immune escape by regulating downstream target molecules such as microRNA or RNA-binding protein.ConclusionCertain circRNAs with important function are expected to become biomarkers for early diagnosis of pancreatic cancer and molecular targets for treatment, so as to achieve goals of early diagnosis and targeted therapy of pancreatic cancer.