EUS Ductal Evaluation in One Endoscopic Session for the Diagnosis of Exocrine Pancreas Disease
EUS Ductal Evaluation in One Endoscopic Session for the Diagnosis of Exocrine Pancreas Disease
The purpose of this study is, to develop a standard of care protocol using the combination of
 EUS, ePFT, and sEUS during one endoscopic session (instead of the three separate endoscopic
 sessions). The desired outcome is to diagnose CP and to establish an acceptable protocol for
 performing this combined technique. It is expected that combining these procedures will
 eliminate redundant portions of the procedures, reduce repeat visits to the hospital, reduce
 total recovery time for the patient, and will decrease the associated costs of separate
 procedures. Chronic pancreatitis (CP) is an irreversible, disease in which the pancreas
 becomes fibrotic ( thickened and scarred). Symptoms almost always include pain, and as the
 pancreas becomes progressively more fibrosed (thickened), pancreatic hormonal function is
 compromised with diarrhea and weight loss. However, while most physicians can readily
 diagnose patients with severe CP, early CP or "minimal-change" CP is difficult to detect,
 often due to the lack of radiologic findings, laboratory tests and classic symptoms. As a
 result, clinicians are searching for diagnostic tools which will allow for earlier, accurate
 detection of this disease, with the hope that appropriate therapy can be initiated before
 extensive thickening and scarring of the pancreas occurs.

 Diagnostic tools to evaluate the pancreas include Endoscopic Ultrasound (EUS),
 hormone-stimulated endoscopic pancreatic function tests (ePFT) and Secretin stimulated
 Endoscopic Pancreas Function Test (sPFT) using pancreatic fluid (containing bicarbonate)
 obtained from the duodenum (the part of the intestine where the stomach opens into the small
 bowel). EUS is increasingly being used as a diagnostic and treatment tool in pancreatic
 disease. Currently, hormone-stimulated ePFT is considered the best way to diagnose chronic
 pancreatitis (long-lasting inflammation and scarring of the pancreas), and removes the need
 for biopsy or surgery. It is also sensitive in detecting mild disease.

 These procedures are standard of care (the normal care you would receive) for the evaluation
 of CP. The purpose of this study, is to develop a standard of care protocol using the
 combination of EUS, ePFT, and sEUS during one endoscopic session, instead of three separate
 endoscopic procedures.
Combined EUS, e-PFT and sEUS Testing:

 The endoscopic procedures for this study will be performed by a single endoscopist at each
 center. It is expected that the combined EUS, ePFT and sEUS will be completed in less than 75
 minutes. Patient sedation will be accomplished via standard conscious (Midazolam, Fentanyl
 and/or Meperidine) sedation or monitored (Propofol) sedation as per the study investigator
 and America Society of Gastrointestinal Endoscopy (ASGE) and American Society of
 Anesthesiology (ASA) guidelines.

 A mechanical-radial EUS echoendoscope with color Doppler assessment capability will be passed
 via standard technique and the pancreas examined from the gastric and duodenal stations.
 Representative EUS images will be recorded on digital videotape/digital snapshot from the
 head, body and tail per the CRF. See Appendix B. These images will then become part of the
 patient's electronic medical record. The echoendoscope will be used to measure specific
 parenchymal (hyperechoic foci with shadowing, hyperechoic strands with shadowing, lobular
 contour, cysts, calculi) and ductal (main ductal diameter, irregularity, hyperechoic margins,
 stones and the presence of visible side branches) abnormalities. It is expected that this
 evaluation will be completed in approximately 10 minutes. Prior to secretin administration
 (baseline MPD diameters), the pancreatic duct diameter will be measured in the head, body,
 and tail using endosonographic calipers. The investigator will provide an initial assessment
 of the presence or absence of chronic pancreatitis prior to secretin administration.

 Next, the echoendoscope will be used to aspirate the gastric and duodenal lumens dry. The
 gastric and duodenal samples will then be discarded.

 Once the gastric and duodenal lumens have been aspirated dry, patients will be given a test
 dose of human secretin of 0.2 mcg (0.1mL) through an indwelling catheter in a peripheral vein
 to assess for a possible allergic response. Patients will be monitored at all times for
 evaluation of hemodynamic instability. If after one minute there is no evidence of an
 allergic reaction, the remaining full dose of secretin 0.2 mcg/kg IV will be given over one
 minute.

 Beginning at time 4 minutes after the completion of secretin intravenous infusion, the
 pancreatic duct diameter will be measured in the head, body, and tail using endosonographic
 calipers. Measurements of the pancreatic duct will occur sequentially at 4, 8, and 12 minutes
 following the conclusion of secretin administration. Representative images will also be
 obtained of each measurement at each time point. The echoendoscope will be used to measure
 specific parenchymal (hyperechoic foci with shadowing, hyperechoic strands with shadowing,
 lobular contour, cysts, calculi) and ductal abnormalities. The investigator will perform a
 follow-up assessment of chronic pancreatitis using additional data on post-secretin
 administration.

 The ePFT portion of the examination will then commence. The echoendoscope will be removed and
 a forward-viewing gastroscope placed into the stomach. Stomach contents will then be
 aspirated dry. The forward-viewing gastroscope will then be placed across the pylorus into
 the distal duodenum. Beginning time 15 minutes following the completion of the secretin
 infusion, duodenal samples (5-10 mL) will be collected through the suction channel of the
 echoendoscope. The samples will be collected in a standard endoscopic collection container
 and placed on ice. At time 30 and 45 minutes after the completion of secretin administation,
 samples will obtained in a similar fashion and placed in separate containers on ice. The
 procedure will then be completed and the patient brought to the same day recovery suite.

 At the conclusion of the procedure, the samples will be brought immediately to the hospital
 chemistry laboratory where they will be evaluated for bicarbonate concentration using the
 hospital autoanalyzer or frozen at -70 degrees Celsius if analysis is delayed. Using the
 autoanalyzer for this technique generally requires a three-fold dilution of the fluid
 contents. The highest bicarbonate concentration from the 3 samples will be considered the
 peak concentration. The diagnostic cut-off for pancreatic exocrine disease will be set at <
 80 mEq/L (80 mEq/L or greater indicates normal function).

 Patient participation in the study will be completed at the time of completion of their
 combined function testing. A telephone call will occur by the PI or designee to each patient
 within 3-7 days of study drug administration will serve as follow-up and complete the CRF.
Inclusion Criteria:

 1. Male or female, between the ages of 18-80 years old.

 2. Clinical suspicion of pancreatic exocrine disease.

 3. If female and not more than 1 year post-menopausal or surgically sterile, must use
 medically acceptable form of contraception or abstain from sexual activity during the
 study. Acceptable methods of birth control are: intrauterine device, implantable
 progesterone device, progesterone intramuscular injection, oral contraceptive (started
 at least one month prior to Screening Visit 1 and continuing for the duration of the
 trial), contraceptive patch, condoms with spermicide or abstinence.

 4. EUS and ePFT planned for structural and functional evaluation of the exocrine
 pancreas.

 5. Ability to undergo conscious sedation or monitored anesthesia.

 6. Willing and able to sign written informed consent.

 Exclusion Criteria:

 1. Symptoms of acute pancreatitis within 30 days of the combined function test.

 2. Severe cardiac disease (stable or unstable angina, congestive heart failure,
 uncontrolled arrhythmias, implantable defibrillator, severe valvular disease, etc).

 3. Severe pulmonary disease (COPD, severe asthma, interstitial lung disease, etc).

 4. Severe renal disease (history of acute or chronic renal failure and/or dialysis
 dependent and/or baseline creatinine >2.0 mg/dL).

 5. Pregnant or nursing.

 6. Ongoing illicit drug use or abuse.

 7. Ongoing moderate or severe alcohol use defined by greater than 30 grams alcohol/day.

 8. Acute pancreatitis as defined by the Atlanta Classification definition (see Appendix
 D) within the previous two months.

 9. Prior pancreatic surgery.

 10. Presence of a condition which may interfere with exocrine pancreatic functioning
 including celiac disease, type I diabetes mellitus, previous gastrectomy, cystic
 fibrosis or severe malnutrition (BMI <18).

 11. Exhibiting signs or symptoms of an episode of acute pancreatitis.

 12. Known allergy to secretin.

 13. Recent (within 30 days) use of medication that can potentially cause pancreatitis,
 such as metronidazole, tetracycline, sulfonamides.

 14. Use of any anticholinergic medication within 48 hours of enrollment.

 15. Any medical condition which in the judgment of the Investigator renders participation
 in this study medically inadvisable.

 16. Participation in an investigational clinical study for a drug or medical device within
 30 days prior to Screening Visit 1.

 17. Suspected or proven Sphincter of Oddi Dysfunction.

 18. Previous pancreatic endoscopic or surgical sphincterotomy

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