Analyzing Intraductal Papillary Mucinous Neoplasms Using Artificial Neural Network Methodologic Triangulation

Intraductal papillary mucinous neoplasms (IPMN) are a type of mucinous pancreatic cyst. IPMN have been shown to be pre-malignant precursors to pancreatic cancer, which has an extremely high mortality rate with average survival less than 1 year. The purpose of this analysis is to utilize methodological triangulation using artificial neural networks and regression to examine the impact and effectiveness of a collection of variables believed to be predictive of malignant IPMN pathology. Results indicate that the triangulation is effective in both finding a new predictive variable and possibly reducing the number of variables needed for predicting if an IPMN is malignant or benign.

A novel staging system and clinical predictive nomogram for more accurate staging and prognosis of malignant pancreatic intraductal papillary mucinous neoplasms: a population-based study

Background The current guidelines of the American Joint Committee on Cancer (AJCC) for the staging of exocrine pancreatic tumors seem inapplicable to malignant pancreatic intraductal papillary mucinous neoplasms (IPMN). Therefore, we aimed to improve the accuracy of clinical staging and prognosis for malignant IPMN by modifiing current AJCC system. Methods We extracted data of 2001 patients with malignant IPMN from the Surveillance, Epidemiology, and End Results database between 2000 and 2016. Of these, 1401 patients were assigned to the primary cohort and 600 patients to the validation cohort. Results In Kaplan–Meier analysis of the primary cohort, the current AJCC guidelines were unable to distinguish between certain tumor substages (IA and IB in the 7th, IB and IIA in the 8th). The modified system that we regrouped based on the median overall survival and hazard ratios, was superior in tumor stage classifications. Age > 70 years, tumors located in the body or tail, high-grade differentiated tumors, surgery, chemotherapy, and tumor, lymph node, and metastasis (TNM) stage were identified as independent predictive factors for overall survival. Compared to that of TNM-based systems, the concordance index of the clinical predictive nomogram significantly improved (0.819; 95% confidence interval, 0.805–0.833), with excellent area under the receiver operating characteristic curves (1-, 3-, and 5-year: 0.881, 0.889, and 0.879, respectively). The calibration curves also showed good agreement between prediction and actual observation. The analysis of treatment modalities revealed that surgery resulted in better survival for all resectable malignant IPMN. The analysis of chemotherapy data reveals its potential in improving the prognosis of treatment for patients with locally advanced or distant metastases. Conclusions Our modified staging system improves the distinction of tumor stages. The nomogram was a more accurate and clinically reliable tool for prognosis prediction of patients with malignant IPMN.

P-P23 Adjuvant chemotherapy in the treatment of intraductal papillary mucinous neoplasms of the pancreas: systematic review and meta-analysis

Background The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. Methods A systematic search of Medline, Pubmed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. Results Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced risk of death in the overall cohort (HR 0.57, 95%-CI:0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95%-CI:0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95%-CI:3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95%-CI:0.20-1.43, p = 0.209). High heterogeneity (I2>75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy were reported for patients with stage III/IV disease, tumour size >2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. Conclusions Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

The association between serum ferritin levels and malignant intraductal papillary mucinous neoplasms

Background Serum ferritin levels are elevated in many malignancies. In this study, we showed the performance of serum ferritin in identifying malignant intraductal papillary mucinous neoplasms (IPMNs). Methods A total of 151 patients with pathologically confirmed IPMNs were enrolled. Serum tumor biomarker (carbohydrate antigen 19–9 (CA19–9) and carcinoembryonic antigen (CEA)) levels and serum ferritin levels were recorded. Lesion location, tumor size, diameter of the main pancreatic duct (MPD), mural nodule, and IPMN type, were collected from imaging examinations. IPMNs with high grade dysplasia and associated invasive carcinoma were considered malignant IPMNs. Results Serum ferritin levels in patients with malignant IPMNs were higher than those in patients with nonmalignant IPMNs (p < 0.05). Serum ferritin was an independent factor for the occurrence of malignant IPMNs (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.01–1.39). A similar trend was found between high serum ferritin (> 149 ng/ml) and malignant IPMNs (OR = 5.64, 95% CI:1.78–17.92). The area under the curve (AUC) of serum ferritin was higher than that of CEA and CA19–9 in identifying malignant IPMNs (AUC = 0.67 vs. AUC = 0.58, 0.65). The combination of serum ferritin with IPMN type showed a similar performance to MPD diameter and the combination of serum CA19–9 with IPMN types in identifying malignant IPMNs (AUC = 0.78 vs. AUC = 0.79, 0.77) and invasive carcinoma (AUC = 0.77 vs. AUC = 0.79, 0.79). Conclusions Elevated serum ferritin is a factor associated with malignant IPMNs. Serum ferritin may be a useful marker for identifying malignancy in IPMNs.

Bioinformatic Analysis and Integration of Transcriptome and Proteome Results Identify Key Coding and Noncoding Genes Predicting Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Background. Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). IPMNs are generally associated with high risk of developing malignancy and therefore need to be diagnosed and assessed accurately, once detected. Existing diagnostic methods are inadequate, and identification of efficient biomarker capable of detecting high-risk IPMNs is necessitated. Moreover, the mechanism of development of malignancy in IPMNs is also elusive. Methods. Gene expression meta-analysis conducted using 12 low-risk IPMN and 23 high-risk IPMN tissue samples. We have also listed all the altered miRNAs and long noncoding RNAs (lncRNAs), identified their target genes, and performed pathway analysis. We further enlisted cyst fluid proteins detected to be altered in high-risk or malignant IPMNs and compared them with fraction of differentially expressed genes secreted into cyst fluid. Results. Our meta-analysis identified 270 upregulated and 161 downregulated genes characteristically altered in high-risk IPMNs. We further identified 61 miRNAs and 14 lncRNAs and their target genes and key pathways contributing towards understanding of the gene regulation during the progression of the disease. Most importantly, we have detected 12 genes altered significantly both in cystic lesions and cyst fluid. Conclusion. Our study reports, for the first time, a meta-analysis identifying key changes in gene expression between low-risk and high-risk IPMNs and also explains the regulatory aspect through construction of a miRNA-lncRNA-mRNA interaction network. The 12-gene-signature could function as potential biomarker in cyst fluid for detection of IPMN with a high risk of developing malignancy.

A Novel Endoscopic Ultrasonography Imaging Technique for Depicting Microcirculation in Pancreatobiliary Lesions without the Need for Contrast-Enhancement: A Prospective Exploratory Study

Detective flow imaging endoscopic ultrasonography (DFI-EUS) provides a new method to image and detect fine vessels and low-velocity blood flow without using ultrasound contrast agents. The aim of this study was to evaluate the utility of DFI-EUS for pancreatobiliary lesions and lymph nodes. Between January 2019 and January 2020, 53 patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS were enrolled. The ability of DFI-EUS and e-FLOW EUS to detect vessels was compared with that of contrast-enhanced EUS. This article describes the DFI technique along with our first experience of its use for vascular assessment of pancreatobiliary lesions. Vessels were imaged in 34 pancreatic solid lesions, eight intraductal papillary mucinous neoplasms (IPMNs), seven gall bladder lesions, and four swollen lymph nodes. DFI-EUS (91%) was significantly superior to e-FLOW EUS (53%) with respect to detection of vessels (p < 0.001) and for discrimination of mural nodules from mucous clots in IPMN and gallbladder lesions from sludge (p = 0.046). Thus, DFI-EUS has the potential to become an essential tool for diagnosis and vascular assessment of various diseases.