This is a non-randomized natural history protocol in which patients undergoing surgery or endoscopy for suspected/ diagnosed pancreaticobiliary strictures are assigned to a) control (chronic pancreatitis, no pancreatic neoplasm, primary sclerosing cholangitis), b) non-carcinoma (bile duct stones, papillary stenosis, ), c) carcinoma non-pancreatic (ampullary and distal bile duct or cholangiocarcinoma) and d) pancreatic ductal adenocarcinoma (pancreatic cancer.

Visit 1 for all participants will consist of going over the Informed Consent form and talking with the patient about the study. If the patient agrees to participate, he/she will be asked to sign the form, and a copy will be given to him/her for his/her records. This will be conducted during the day of the endoscopic procedure before the participant is under anesthesia.

Consented participants will have 20ml of blood collected via venipuncture of peripheral vein drawn by the endoscopy unit staff during their endoscopy procedure. The blood will be collected into heparinized vacutainers and immediately labeled with study specific code identifier and placed at 4⁰C until processed (within 24hr).

For clinical purposes, tissue may be removed during the endoscopic procedures. This tissue will be given to the Diagnostic Pathology (DP) personnel associated with the case for analysis. The diagnostic sample will be processed for DP use and stored in the DP active archives. No additional tissue will be taken solely for the purposes of this research study. However, if DP approves the use of the remaining clinical diagnostic, small cores or slides will be taken after the diagnostic use from the approved paraffin-embedded tissue blocks for use in comparison/confirmatory analyses to the bile and blood analyses done for this research project.

During the endoscopic procedures a 5ml aspiration of bile fluid will be collected for this study with the endoscopic instrument. The fluid will be transferred to a sterile tube, sealed, and placed at 4⁰C until processed (within 24hr). Both blood and fluids samples will be transferred to Translational Research Institute (TRI) R&D for analysis.

Follow Up (follow up will take place for all groups listed on page 7 of the protocol under "Study Design" with the exception of group B) 2 weeks post procedure- A member of the research staff will call the participant to assess for any complications Periodic medical record auditing for outcome data will be collected every three months for up to 1 year after enrollment.

One year post procedure- A member of the research staff will call the participant to assess for any complications

Inclusion Criteria:

Screening Criteria for Potential Participants in the Study

1. Age: ≥18years old
2. Treatment: scheduled for clinical reason to undergo an ERCP at the CIE
3. Suspected of having biliary or pancreatic disease other than cancer (chronic pancreatitis, benign biliary strictures, post-liver transplant strictures, common bile duct stones, sphincter of Oddi dysfunction or suspected of having pancreatic or peri-ampullary malignancy (including pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary carcinoma, duodenal, carcinoma
4. Clinical or image data suggestive of pancreatic disease or the need for gastrointestinal or pancreatic inspection.
5. Willing and mentally able to provide consent

Exclusion Criteria:

1. Age: <18years old
2. Pregnant women
3. Post-bariatric surgery, hepaticojejunostomy and Bilroth II patients undergoing ERCP.
4. Not scheduled for endoscopic procedures for clinical reasons
5. No clinical or image data suggestive of need for clinical intervention (Endoscopy)
6. Not willing or able to sign informed consent..

Patients scheduled for ERCP at the Center for Interventional Endoscopy (CIE)