Inclusion Criteria - All Groups:

• All participants must sign an informed consent indicating that they are aware of the investigational nature of this study and willing to undergo study interventions, and authorizing the use of their protected health information for research purposes.
• Meet one set of group-specific inclusion criteria listed below.
• All participants must be ≥ 18 years old and ≤ 75 years at the time of enrollment.

Inclusion Criteria - No Pancreas Disease Controls:

• No personal history or symptoms of pancreatic disease.
• No upper abdominal symptoms
• *Participant will answer “No” and “None” to below questions to meet this criterion:
  • Have you had a stomach ache or pain more than SIX times in the past year?
  • □ YES            □ NO
• How many times have you had a feeling of WANTING TO THROW UP (nausea) in the last year?
  • □ NONE        □ ANY
• No family history of pancreatic disorders, celiac disease, cystic fibrosis.
• No history of acute infectious or inflammatory conditions requiring medical treatment or evaluation in the preceding 6 months (per provider clinical judgment).
• No history of cancer, except for non-melanoma skin cancers.
• No known pregnancy at the time of enrollment.
• No solid organ transplant or history of HIV/AIDS.
• Able to provide an informed consent.
• Not currently incarcerated.
• ASA 1-2.

Inclusion Criteria - Chronic Upper Abdominal Pain of Suspected Pancreatic Origin:

• Referred to a pancreas or GI clinic or admitted to the hospital for evaluation of unexplained upper abdominal pain of at least 3 months in duration for which a pancreatic origin is clinically considered in the differential diagnosis.*

* Pancreatic type pain is defined as epigastric pain that is often constant, often worsens post-prandially, and may radiate to the back. This can often be associated with lipase/amylase elevations that do not meet the threshold for diagnosis of AP (i.e. <3-fold upper limit of normal).

• No history of AP or CP.
• No prior endoscopic sphincterotomy or pancreatic surgery.
• Normal cross-sectional abdominal imaging (CT and MRI/MRCP).**

** CT and MRI/MRCP must be performed ≤24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment as “Chronic Abdominal Pain – Undifferentiated”. The second imaging study can be performed in this situation after the enrollment and the final assignment into the appropriate subgroup can be done after review of the imaging results.

• If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation and attempts will be made to complete this during follow-up as feasible. If the second study could not be performed, the subject will be assigned to Chronic upper abdominal pain group if the available study was normal or as Indeterminate CP if the available study shows Cambridge 1-2 findings.

Inclusion Criteria - Indeterminate CP with no history of AP:

• Referred to a pancreas or GI clinic or admitted to the hospital for evaluation of unexplained upper abdominal pain of at least 3 months in duration for which a pancreatic origin is clinically considered in the differential diagnosis*

* Pancreatic type pain is defined as epigastric pain that is often constant, often worsens post-prandially, and may radiate to the back. This can often be associated with lipase/amylase elevations that do not meet the threshold for diagnosis of AP (i.e. <3-fold upper limit of normal).

• No history of AP or CP.**

**AP is defined as compatible symptoms (upper abdominal pain) together with A) ≥ 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR).

• Cambridge grade I-II changes of CP# on cross-sectional imaging (CT or MRI/MRCP).***

*** CT and MRI/MRCP must be performed ≤24 months prior to enrollment OR within 6 months after study enrollment.  CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment as “Chronic Abdominal Pain – Undifferentiated”. The second imaging study can be performed in this situation after the enrollment and the final assignment into the appropriate subgroup can be done after review of the imaging results.

• If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation and attempts will be made to complete this during follow-up as feasible. If the second study could not be performed by month 6 after enrollment, the subject will be assigned to Chronic upper abdominal pain group if the available study was normal or as Indeterminate CP if the available study shows Cambridge 1-2 findings. 
• No prior endoscopic sphincterotomy or pancreatic surgery.

Inclusion Criteria - Acute Pancreatitis (AP):

•  History of one documented attack of AP in the preceding 18 months.*

* AP is defined as compatible symptoms (upper abdominal pain) together with A) ≥ 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR). Patient should not have had an attack of AP in the month prior to enrollment.

• Patients should not have had an ERCP prior to the episode of AP.
• Pancreatitis episode is not attributable to gallstones (i.e., suspected or definite biliary etiology), medications, trauma or autoimmune pancreatitis.
• Pancreatic necrosis, if present, is <50% (to be verified by a CPDPC site radiologist).
• Cambridge grade < III changes of CP# on cross-sectional imaging (CT or MRI/MRCP).***

*** CT and MRI/MRCP must be performed ≤ 24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment. The second study  can be performed in this situation after the enrollment.

• If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation. Final group assignment in this situation will be based on the available study.   
• No prior pancreatic surgery.

Inclusion Criteria - Recurrent Acute Pancreatitis (RAP):

• Two or more documented attacks of AP* separated by at least 1 month, with complete symptom resolution between the attacks.

* AP is defined as compatible symptoms (epigastric pain with nausea or vomiting) together with A) ≥ 3-fold elevation of serum amylase and/or lipase above upper limit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/or MR).

• Patient should not have had an ERCP prior to having first documented attack of pancreatitis.
• Cambridge grade < III changes of CP# on cross-sectional imaging (CT or MRI/MRCP)**

**CT and MRI/MRCP must be performed ≤24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment. The second study can be performed in this situation after the enrollment.

• Cambridge grade < III changes of CP# on cross-sectional imaging (CT or MRI/MRCP).**

**CT and MRI/MRCP must be performed ≤24 months prior to enrollment OR within 6 months after study enrollment. CT and MRI scans must be intravenous contrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP without secretin prior to enrollment is acceptable at baseline to be used for enrollment). If the patient has had only one imaging study, the patient is eligible for enrollment. The second study can be performed in this situation after the enrollment.

• If the second study was planned within 6 months after enrollment but could not be completed, it will not be considered as eligibility violation. Final assignment in this situation will be based on the available study.
• In a rare circumstance, the last imaging patient had was >24 months prior to enrollment. In this circumstance, the patient is still eligible for enrollment, and can undergo CT scan first, and if there is no evidence of Cambridge 3-4 findings, undergo an MRI/MRCP to fulfill entry criteria. If the planned studies could not be completed within 6 months after enrollment, the final group assignment will be in this situation will be based on the available study.
• Pancreatitis episodes are not attributable to gallstones, medications, trauma or autoimmune pancreatitis.
• No prior pancreatic surgery.

Inclusion Criteria - Definite Chronic Pancreatitis

• Presence of unequivocal CP (i.e., Cambridge grade ≥ 3) and/or parenchymal and/or ductal calcifications by cross-sectional imaging (IV contrast-enhanced MRI/MRCP or CT) verified by the CPDPC site radiologist.*

* Must exclude the possibility that calcifications are vascular. Calcifications noted by EUS only (and not correlated with CT) are not included as definite CP. A non-contrast CT scan or MRI/MRCP documenting definite CP as per criteria is acceptable for enrollment.

• Pancreatic histology diagnostic of CP (including findings of fibrosis [Ammann’s ≥ 6], chronic inflammation, and acinar loss) as verified by a CPDPC site pathologist, if pathology slides are available for review.

Exclusion Criteria:

• History of autoimmune or traumatic pancreatitis, or sentinel attack of acute necrotizing pancreatitis which   results in suspected disconnected duct syndrome.
• Primary pancreatic tumors - pancreatic ductal adenocarcinoma, suspected cystic neoplasm (> 1 cms in size or main duct involvement), neuroendocrine tumors, and other uncommon tumors. 
• Pancreatic metastasis from other malignancies.
• History of solid organ transplant, HIV/AIDS.
• Known isolated pancreatic exocrine insufficiency (e.g., in the absence of any eligible inclusion criteria).
• Participants must not have medical or psychiatric illnesses or ongoing substance abuse that in the investigator’s opinion would compromise their ability to tolerate study interventions or participate in longitudinal follow up.
• Patients with known abnormal creatinine (GFR < 30) or renal failure (applies to patients with chronic upper abdominal pain of suspected pancreatic origin and suspected CP (yellow) subgroups).
• Failure to agree for longitudinal follow-up.
• Known Pregnancy. All participants of childbearing potential, except if post-menopausal [i.e., no menses for ≥ 2 years] or had a hysterectomy, bilateral tubal ligation/clip (surgical sterilization) or surgical removal of both the ovaries), must have a negative urine or serum B-HCG pregnancy test documented within 2 days prior to any endoscopic or radiologic procedures done for research purposes. Any standard of care tests will follow institutional policies regarding pregnancy test.
• Currently incarcerated.
• Inability to get MRI/MRCP in patients with chronic abdominal pain of suspected pancreatic origin (Green II) or Suspected CP (Yellow groups) at baseline (e.g., metal object in the body which precludes performance of MRI).