Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in our understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21190

Recent Progress in Pancreatic Cancer

PDAC is an aggressive disease and early infiltrates peripancreatic tissues and adjacent organs, and gives distant metastasis and peritoneal involvement, making often surgical resection impossible. About 80% of PDACs are inoperable at the time of diagnosis. However, even if radiologically resectable, some PDAC microscopically involves the resection margins (pancreatic, retroperitoneal, or biliary, the retroperitoneal being the most important because it cannot be evaluated intraoperatorially) resulting in a nonradical excision. Local aggressiveness consists in the invasion of contiguous structures and organs (spleen, stomach, left adrenal gland, colon, and peritoneum), whereas distant metastases can occur in liver, lungs, adrenals, kidneys, bones, brain, and skin.

Pathology and Genetics

Background: Serum carbohydrate antigen (CA 19-9) is the most common tumor marker assessed in pancreatic cancer patients; nevertheless few articles have comprehensively evaluated the evidence for its utility in pancreatic cancer management.
 Methods: Literature search was performed using Medline with keywords “pancreatic cancer” “tumor markers” “CA 19-9” “diagnosis” “screening” “prognosis” “resectability” and “recurrence”. All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer.
 Results: Serum CA 19-9 is the most extensively validated pancreatic cancer biomarker with multiple clinical applications. CA 19-9 serum levels have a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients; but are not useful as a screening marker because of low positive predictive value (0.5-0.9%). Pre-operative CA 19-9 serum levels provide useful prognostic information as patients with normal levels ( 37 U/ml) (12-15 months). A CA 19-9 serum level of 100 U/ml suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥ 20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an increase. Important limitations to CA 19-9 serum level evaluation in pancreatic cancer include poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%).
 Conclusion: CA 19-9 is the most extensively studied and validated serum biomarker for the diagnosis of pancreatic cancer in symptomatic patients. CA 19-9 serum levels can provide important information with regards to prognosis, overall survival, and response to chemotherapy as well as predict post-operative recurrence. However, non-specific expression in several benign and malignant diseases, false negative results in Lewis negative genotype and an increased false positive results in the presence of obstructive jaundice severely limit the universal applicability of serum CA 19-9 levels in pancreatic cancer management.

/pdf/the-clinical-utility-of-serum-ca-19-9-in-the-diagnosis-2mrkxzum22.pdf

The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal

Summary: The GeneMANIA Cytoscape plugin brings fast gene function prediction capabilities to the desktop. GeneMANIA identifies the most related genes to a query gene set using a guilt-by-association approach. The plugin uses over 800 networks from six organisms and each related gene is traceable to the source network used to make the prediction. Users may add their own interaction networks and expression profile data to complement or override the default data.

Availability and Implementation: The GeneMANIA Cytoscape plugin is implemented in Java and is freely available at http://www.genemania.org/plugin/.

Contact:gary.bader@utoronto.ca; quaid.morris@utoronto.ca

/pdf/genemania-cytoscape-plugin-1v476pwvva.pdf

GeneMANIA Cytoscape plugin

The evolution of mass spectrometry-based proteomic technologies has advanced our understanding of the complex and dynamic nature of proteomes while concurrently revealing that no 'one-size-fits-all' proteomic strategy can be used to address all biological questions. Whereas some techniques, such as those for analyzing protein complexes, have matured and are broadly applied with great success, others, such as global quantitative protein expression profiling for biomarker discovery, are still confined to a few expert laboratories. In this Perspective, we attempt to distill the wide array of conceivable proteomic approaches into a compact canon of techniques suited to asking and answering specific types of biological questions. By discussing the relationship between the complexity of a biological sample and the difficulty of implementing the appropriate analysis approach, we contrast areas of proteomics broadly usable today with those that require significant technical and conceptual development. We hope to provide nonexperts with a guide for calibrating expectations of what can realistically be learned from a proteomics experiment and for gauging the planning and execution effort. We further provide a detailed supplement explaining the most common techniques in proteomics.

https://ccsb.stanford.edu/content/dam/sm/ccsb/documents/education/cbio243course/2010_Mallick_Proteomics_a_pragmatic_perspective.pdf

Proteomics: a pragmatic perspective

Akhilesh Pandey and colleagues describe a compendium of potential biomarkers that can be systematically validated by the pancreatic cancer community.

/pdf/a-compendium-of-potential-biomarkers-of-pancreatic-cancer-ply1t1b37u.pdf

A Compendium of Potential Biomarkers of Pancreatic Cancer

Availability of a freely accessible, dynamic and integrated database for primary immunodeficiency diseases (PID) is important both for researchers as well as clinicians. To build a PID informational platform and also as a part of action to initiate a network of PID research in Asia, we have constructed a web-based compendium of molecular alterations in PID, named Resource of Asian Primary Immunodeficiency Diseases ( RAPID), which is available as a worldwide web resource at http://rapid.rcai.riken.jp/. It hosts information on sequence variations and expression at the mRNA and protein levels of all genes reported to be involved in PID patients. The main objective of this database is to provide detailed information pertaining to genes and proteins involved in primary immunodeficiency diseases along with other relevant information about protein-protein interactions, mouse studies and microarray gene-expression profiles in various organs and cells of the immune system. RAPID also hosts a tool, mutation viewer, to predict deleterious and novel mutations and also to obtain mutation-based 3D structures for PID genes. Thus, information contained in this database should help physicians and other biomedical investigators to further investigate the role of these molecules in PID.

Sashikanth Gollapudi

Papers

A Compendium of Potential Biomarkers of Pancreatic Cancer

RAPID: Resource of Asian Primary Immunodeficiency Diseases