Stool Testing for Pancreatic Cancer
Condition: Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Observational

Summary: 
      The purpose of this study is to determine if pancreatic cancer/pre-cancer can be detected in
      early stages through the molecular analysis of stool samples. Investigators hypothesize that
      analysis of stool samples using digital melt curve (DMC) analysis, can be used as a sensitive
      and specific method to detect the common genetic abnormalities present in pancreatic cancers
      and pre-cancerous lesions of the pancreas.
    

Detailed description: 
      Pancreatic ductal adenocarcinoma (PDC) remains the fourth leading cause of cancer-related
      death in the United States. This is largely due to the fact that most patients present with
      advanced, unresectable disease, highlighting the critical need for a screening test for this
      disease. Stool testing is an approach that has not been explored for use in PDC screening.
      With the advent of stool-based DNA tests, it may be possible to target genetic abnormalities
      that have been recently characterized in PDC tumorigenesis.

      Aim: The aim of this study is to determine if deoxyribonucleic acid (DNA) alterations present
      in pancreatic cancer and precancerous intrapapillary mucinous neoplasms (IPMN) can be
      reliably recovered in matched stool.

      Methods: This is a case-control prospective study to determine the utility of a stool-based
      digital melt curve (DMC) assay in PDC screening. A total of 30 patients (18 with pancreatic
      cancer, 12 with IPMN) who will be undergoing pancreatic resection will be enrolled.
      Pancreatic neoplastic tissue will be isolated from their surgical specimens and the genes
      most commonly mutated in PDC will be sequenced from extracted DNA. In addition,
      hypermethylation at common promoter sites will be assessed by methylation-specific PCR. The
      genetic and epigenetic alterations isolated in pancreatic tissue will be utilized as the
      targets for stool DMC assay. Blinded technicians will process stool specimens from control
      patients as well as a matched control. The primary outcomes of this study will be the
      sensitivity and specificity of the stool DMC assay in detecting genetic mutations present in
      tumor or IPMN lesions.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Individuals with a diagnosis of pancreatic cancer/IPMN who are scheduled for surgical
        resection at Columbia University Medical Center's Pancreas Center will be accrued to this
        study.
      
Biospecimen description: 
      -  Tissue Collection: Fresh frozen resected tumor and IPMN tissue will be obtained whenever
           possible. All resected specimens, cancer and IPMN, will have histologic review to
           confirm the diagnosis. Ten slices of 10 microns each from each specimen will be prepared
           and sent to Mayo Clinic on dry ice.

        -  Stool Collection: Prior to any surgery, stool will be collected from both study and
           control patients. Collection containers and mailing materials will be provided to
           subjects at time of their recruitment. Stool specimens will be mailed directly to Mayo
           Clinic within 48 hours of collection. Stool will be stored at 80 °C until assayed.

        -  Stool DNA extraction: After stool is homogenized, crude stool DNA will be extracted and
           purified.

        -  Digital melt curve mutation analysis: Target gene copies in captured stool DNA and
           tissue DNA will be quantified with real-time PCR. To target the mutations detected in
           tumor specimens, we will utilize PCR primers that scan for specific gene abnormalities.
    
Keywords: Pancreatic Cancer; Intraductal Papillary Mucinous Neoplasm (IPMN); Stool-based digital melt curve (DMC) assay; Surgical resection for pancreatic cancer; Hereditary Pancreatic Cancer Syndrome; Genetic mutations linked to pancreatic cancer