Clinical usefulness of scoring systems to predict severe acute pancreatitis : A systematic review and meta-analysis with pre and post-test probability assessment

Scoring systems for severe acute pancreatitis (SAP) prediction should be used in conjunction with pre-test probability to establish post-test probability of SAP, but data of this kind are lacking.To investigate the predictive value of commonly employed scoring systems and their usefulness in modifying the pre-test probability of SAP.Following PRISMA statement and MOOSE checklists after PROSPERO registration, PubMed was searched from inception until September 2022. Retrospective, prospective, cross-sectional studies or clinical trials on patients with acute pancreatitis defined as Revised Atlanta Criteria, reporting rate of SAP and using at least one score among Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Examination (APACHE)-II, RANSON, and Systemic Inflammatory Response Syndrome (SIRS) with their sensitivity and specificity were included. Random effects model meta-analyses were performed. Pre-test probability and likelihood ratio (LR) were combined to estimate post-test probability on Fagan nomograms. Pooled severity rate was used as pre-test probability of SAP and pooled sensitivity and specificity to calculate LR and generate post-test probability. A priori hypotheses for heterogeneity were developed and sensitivity analyses planned.43 studies yielding 14,116 acute pancreatitis patients were included: 42 with BISAP, 30 with APACHE-II, 27 with Ranson, 8 with SIRS. Pooled pre-test probability of SAP ranged 16.6%-25.3%. The post-test probability of SAP with positive/negative score was 47%/6% for BISAP, 43%/5% for APACHE-II, 48%/5% for Ranson, 40%/12% for SIRS. In 18 studies comparing BISAP, APACHE-II, and Ranson in 6740 patients with pooled pre-test probability of SAP of 18.7%, post-test probability when scores were positive was 48% for BISAP, 46% for APACHE-II, 50% for Ranson. When scores were negative, post-test probability dropped to 7% for BISAP, 6% for Ranson, 5% for APACHE-II. Quality, design, and country of origin of the studies did not explain the observed high heterogeneity.The most commonly used scoring systems to predict SAP perform poorly and do not aid in decision-making

Needle-Tract Seeding of Pancreatic Cancer after EUS-FNA: A Systematic Review of Case Reports and Discussion of Management

Needle-tract seeding (NTS) has been sporadically reported as complication of Endoscopic Ultrasound (EUS)-guided aspiration (FNA) in pancreatic adenocarcinoma (PDAC). However, the evidence of its treatment and outcome is sparse. Adhering to PRISMA guidelines, we conducted a systematic review of EUS-FNA NTS cases of PDAC and analyzed their management and outcome. Up to September 2022, the search query retrieved forty-five cases plus an unpublished case from our center, for a total of forty-six; 43.6% were male, with a mean age of 68.6 years. Thirty-four patients (87.1%) underwent an initial surgical resection, with only 44.1% and 5.9% undergoing adjuvant and neoadjuvant chemotherapy, respectively, and 5.9% undergoing both. The NTS nodule was mostly located in the posterior gastric wall, developing at a median of 19 months after primary resection; 82.4% underwent surgical resection of the seeding, while for 17.6%, palliative chemotherapy treatment. Follow-up after NTS diagnosis and treatment was reported for only twenty-three patients: when NTS was treated with surgery, the median overall survival was 26.5 months compared to 15.5 if treated with radio/chemotherapy. NTS after EUS-FNA of PDAC occurs late and might be treated aggressively with good results. Interestingly, only a low number of patients developing NTS underwent chemotherapy for the primary cancer, suggesting its possible protective role

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer:A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. Background: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. Materials and Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: CRD42022300408). Results: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I 2: 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I 2: 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P&lt;0.01). Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.</p

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer:A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. Background: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. Materials and Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: CRD42022300408). Results: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I 2: 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I 2: 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P&lt;0.01). Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.</p

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence meta-analysis to Estimate the Rate of low-yield Surgery

Objective: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. Summary background data: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRI) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well-quantified. Methods: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the CAPS goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408). Results: Twenty-three articles with 5,027 patients (median 109 patients/study, IQR 251) were included. The pooled prevalence of low-yield surgery was 2.1% [95%CI 0.9-3.7], I2 83%). In the subgroup analysis, this prevalence was non-significantly higher in studies that only included familial pancreatic cancer (FPC) subjects without known pathogenic variants (PV), compared to those enrolling PV carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% [95%CI 0.3-1.5], I2 24%). The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P&lt;0.01). Conclusions: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance

A scan of all coding region variants of the human genome, identifies 13q12.2-rs9579139 and 15q24.1-rs2277598 as novel risk loci for pancreatic ductal adenocarcinoma

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 x 10(-9)), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 x 10(-6)). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting re-analysis of genome-wide association studies (GWASs) in light of functional data.[GRAPHICS]

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk