Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies, the PROCEED Study

Inclusion Criteria:

• ALL GROUPS: All participants must sign an informed consent indicating that they areaware of the investigational nature of this study and willing to undergo studyinterventions, and authorizing the use of their protected health information forresearch purposes
• ALL GROUPS: Meet one set of group-specific inclusion criteria listed below
• ALL GROUPS: All participants must be >= 18 years old and =< 75 years at the time ofenrollment
• NO PANCREATIC DISEASE: No personal history or symptoms of pancreatic disease
• NO PANCREATIC DISEASE: No upper abdominal symptoms
• NO PANCREATIC DISEASE: No family history of pancreatic disorders, celiac disease,cystic fibrosis
• NO PANCREATIC DISEASE: No history of acute infectious or inflammatory conditionsrequiring medical treatment or evaluation in the preceding 6 months (per providerclinical judgment)
• NO PANCREATIC DISEASE: No history of cancer, except for non-melanoma skin cancers
• NO PANCREATIC DISEASE: No known pregnancy at the time of enrollment
• NO PANCREATIC DISEASE: No solid organ transplant or history of human immunodeficiencyvirus/acquired immunodeficiency syndrome (HIV/AIDS)
• NO PANCREATIC DISEASE: Able to provide an informed consent
• NO PANCREATIC DISEASE: Not currently incarcerated
• NO PANCREATIC DISEASE: American Society of Anesthesiologists (ASA) 1-2
• CHRONIC UPPER ABDOMINAL PAIN: Referred to a pancreas or gastrointestinal (GI) clinicor admitted to the hospital for evaluation of unexplained upper abdominal pain of atleast 3 months in duration for which a pancreatic origin is clinically considered inthe differential diagnosis
• Pancreatic type pain is defined as epigastric pain that is often constant, oftenworsens postprandially, and may radiate to the back. This can often be associatedwith lipase/amylase elevations that do not meet the threshold for diagnosis ofacute pancreatitis (AP) (i.e. < 3-fold upper limit of normal)
• CHRONIC UPPER ABDOMINAL PAIN: No history of AP or CP
• CHRONIC UPPER ABDOMINAL PAIN: No prior endoscopic sphincterotomy or pancreatic surgery
• CHRONIC UPPER ABDOMINAL PAIN: Normal cross-sectional abdominal imaging (CT andMRI/Magnetic resonance cholangiopancreatography [MRCP])
• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6months after study enrollment. CT and MRI scans must be intravenouscontrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP withoutsecretin prior to enrollment is acceptable at baseline to be used forenrollment). If the patient has had only one imaging study, the patient iseligible for enrollment as "Chronic Abdominal Pain - Undifferentiated". Thesecond imaging study can be performed in this situation after the enrollment andthe final assignment into the appropriate subgroup can be done after review ofthe imaging results. If the second study was planned within 6 months afterenrollment but could not be completed, it will not be considered as eligibilityviolation and attempts will be made to complete this during follow- up asfeasible. If the second study could not be performed, the subject will beassigned to chronic upper abdominal pain group if the available study was normalor as indeterminate CP if the available study shows Cambridge 1-2 findings
• INDETERMINATE CP: Referred to a pancreas or GI clinic or admitted to the hospital forevaluation of unexplained upper abdominal pain of at least 3 months in duration forwhich a pancreatic origin is clinically considered in the differential diagnosis
• Pancreatic type pain is defined as epigastric pain that is often constant, oftenworsens postprandially, and may radiate to the back. This can often be associatedwith lipase/amylase elevations that do not meet the threshold for diagnosis of AP (i.e. < 3-fold upper limit of normal)
• INDETERMINATE CP: 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)
• INDETERMINATE CP: Cambridge grade I-II changes of CP on cross-sectional imaging (CT orMRI/MRCP)
• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6months after study enrollment. CT and MRI scans must be intravenouscontrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP withoutsecretin prior to enrollment is acceptable at baseline to be used forenrollment). If the patient has had only one imaging study, the patient iseligible for enrollment as "Chronic Abdominal Pain - Undifferentiated". Thesecond imaging study can be performed in this situation after the enrollment andthe final assignment into the appropriate subgroup can be done after review ofthe imaging results. If the second study was planned within 6 months afterenrollment but could not be completed, it will not be considered as eligibilityviolation and attempts will be made to complete this during follow- up asfeasible. 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 theavailable study was normal or as indeterminate CP if the available study showsCambridge 1-2 findings
• INDETERMINATE CP: No prior endoscopic sphincterotomy or pancreatic surgery
• 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). Patientshould not have had an attack of AP in the month prior to enrollment.
• Patients should not have had an endoscopic retrogradecholangiopancreatography (ERCP) prior to the episode of AP
• AP: Pancreatitis episode is not attributable to gallstones (i.e. suspected or definitebiliary etiology), medications, trauma or autoimmune pancreatitis
• AP: Pancreatic necrosis, if present, is < 50% (to be verified by a ChronicPancreatitis, Diabetes and Pancreatic Cancer [CPDPC] site radiologist)
• AP: 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 6months after study enrollment. CT and MRI scans must be intravenouscontrast-enhanced and MRCP with secretin (a non contrast MRI and MRCP withoutsecretin prior to enrollment is acceptable at baseline to be used forenrollment). If the patient has had only one imaging study, the patient iseligible for enrollment. The second study can be performed in this situationafter the enrollment. If the second study was planned within 6 months afterenrollment but could not be completed, it will not be considered as eligibilityviolation. Final group assignment in this situation will be based on theavailable study
• AP: No prior pancreatic surgery
• RECURRENT AP: Two or more documented attacks of AP separated by at least 1 month, withcomplete 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 upperlimit of normal, AND/OR B) features of AP on cross-sectional imaging (CT and/orMR).
• Patient should not have had an ERCP prior to having first documented attackof pancreatitis
• RECURRENT AP: Cambridge grade < III changes of CP on cross-sectional imaging (CT orMRI/MRCP)
• CT and MRI/MRCP must be performed =< 24 months prior to enrollment OR within 6months after study enrollment. CT and MRI scans must be intravenouscontrast-enhanced and MRCP with secretin (a non-contrast MRI and MRCP withoutsecretin prior to enrollment is acceptable at baseline to be used forenrollment). If the patient has had only one imaging study, the patient iseligible for enrollment. The second study can be performed in this situationafter the enrollment. If the second study was planned within 6 months afterenrollment but could not be completed, it will not be considered as eligibilityviolation. Final assignment in this situation will be based on the availablestudy. In a rare circumstance, the last imaging patient had was > 24 months priorto enrollment. In this circumstance, the patient is still eligible forenrollment, and can undergo CT scan first, and if there is no evidence ofCambridge 3-4 findings, undergo an MRI/MRCP to fulfill entry criteria. If theplanned studies could not be completed within 6 months after enrollment, thefinal group assignment will be in this situation will be based on the availablestudy
• RECURRENT AP: Pancreatitis episodes are not attributable to gallstones, medications,trauma or autoimmune pancreatitis
• RECURRENT AP: No prior pancreatic surgery
• DEFINITE CP: Presence of unequivocal CP (i.e. Cambridge grade >= 3) and/or parenchymaland/or ductal calcifications by cross-sectional imaging (IV contrast-enhanced MRI/MRCPor CT) verified by the CPDPC site radiologist
• Must exclude the possibility that calcifications are vascular. Calcificationsnoted by EUS only (and not correlated with CT) are not included as definite CP. Anon-contrast CT scan or MRI/MRCP documenting definite CP as per criteria isacceptable for enrollment
• DEFINITE CP: Pancreatic histology diagnostic of CP (including findings of fibrosis [Ammann's >= 6], chronic inflammation, and acinar loss) as verified by a CPDPC sitepathologist, if pathology slides are available for review

Exclusion Criteria:

• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: History of autoimmune or traumaticpancreatitis, or sentinel attack of acute necrotizing pancreatitis which results insuspected disconnected duct syndrome
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Primary pancreatic tumors - pancreatic ductaladenocarcinoma, suspected cystic neoplasm (> 1 cms in size or main duct involvement),neuroendocrine tumors, and other uncommon tumors
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Pancreatic metastasis from other malignancies
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: History of solid organ transplant, HIV/AIDS
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Known isolated pancreatic exocrineinsufficiency (e.g. in the absence of any eligible inclusion criteria)
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Participants must not have medical orpsychiatric illnesses or ongoing substance abuse that in the investigator's opinionwould compromise their ability to tolerate study interventions or participate inlongitudinal follow up
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Patients with known abnormal creatinine (glomerular filtration rate [GFR] < 30) or renal failure (applies to patients withchronic upper abdominal pain of suspected pancreatic origin and suspected CP [yellow]subgroups)
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Failure to agree for longitudinal follow-up
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Known pregnancy. All participants ofchildbearing potential, except if post-menopausal [i.e. no menses for >= 2 years] orhad a hysterectomy, bilateral tubal ligation/clip (surgical sterilization) or surgicalremoval of both the ovaries), must have a negative urine or serum human chorionicgonadotropin (B-HCG) pregnancy test documented within 2 days prior to any endoscopicor radiologic procedures done for research purposes. Any standard of care tests willfollow institutional policies regarding pregnancy test
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Currently incarcerated
• ALL GROUPS EXCEPT NO PANCREATIC DISEASE: Inability to get MRI/MRCP in patients withchronic abdominal pain of suspected pancreatic origin (Green II) or suspectedCP(Yellow groups) at baseline (e.g. metal object in the body which precludesperformance of MRI)