John GLieb II MD Assistant Professor of Clinical Medicine 6272014 Golden Rule Eat when you can Sleep when you can and Dont touch the pancreas House of God Outline Chronic Pancreatitis ID: 1042179
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1. Pancreatic Function TestingJohn G.Lieb II MDAssistant Professor of Clinical Medicine6/27/2014
2. Golden RuleEat when you canSleep when you can and…Don’t touch the pancreas!House of God
3. OutlineChronic Pancreatitis def, epidemiol, causesSpectrum of chronic pancreatitisWhen does steatorrhea occur, why, how, so what?Panc funct tests vs other tests for chronic pancStool/indirect Panc function testsDirect (often tube) panc function testsFuture Panc function testsCases
4. A Few Key Pearls for Chronic PancreatitisWhat is CP?There is very little evidence based medicine.Make the correct diagnosis.Stage the disease.Base therapy on the stage/etiology of disease.
5. What is CP?“Irreversible” damageHistologic evidence of inflammation, fibrosis, and destruction of exocrine (acinar) and endocrine (islet) tissue.Can be inferred by clinical evidence of Exocrine (secretory) and endocrine insufficiency.Obvious structural disease on radio.Calcifications, multiple beads and stricturesThe first three dogma being challengedPain or steatorrhea not necessary
6. Etiology of CPIDIOPATHICALCOHOL & TOBACCOHEREDITARYLieb and Toskes, Hosp Phys. Brd Rvw 2007
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8. Make the Correct DiagnosisChronically elevated amy/lip do not CP makeGullo’s1, vomitting, opiatesIn early CP, imaging and labs may be negative or equivocalAvoid labelling as CPAvoid sick role, pyschosocialeconomic consequen.Much acute relapsing pancreatitis is actually early chronic pancreatitisGullo L. JOP. 2006 Mar 9;7(2):241-2;
9. Consequences of Chronic PancPainSteatorrheaDiabetesBiliary obsB12 defCancer
10. Is Steatorrhea Present?Consequences are significantTreatment is chronic and expensive3-5$/enzyme pillInsurance co’s may require proofNow you have proven advanced chronic panc
11. Steatorrhea/Exocrine InsufficiencyHappens at 90% destruction of pancreasNonlinear, cliff
12. Consequences of SteatorrheaWeight loss/underweightVit A, D, K, E, B12 deficienciesMagnesium deficiencyOsteoporosisLow HDLHigher mortality in CP patients. From this?Oxalate renal stones
13. Is the Steatorrhea from the Pancreas?Non pancreatic steatorrhea quite commonMany pancreas patients have coexisting small bowel bacterial overgrowth or even sprueAutoimmune CP patients often have IBD
14. Diagnosis of CPStructural TestsCTMRI/MRCPEUSFunction TestsFecal fatSerum TrypsinFecal ElastaseGlucose/GTTPanc.PolypeptideS-MRCPS-EUSSSTE-SST
15. Pancreatic Function Tests (PFTs)Indirect (often tubeless)Fecal fatTrypsinGlucose/GGTPanc.polypeptideDual Label Schilling testDirectS-MRCPS-EUSeSSTSSTCCK/SSTBentiromide test (historical)Lundh test (Europe)
16. Tests to Diagnose CPEASY ON PTSTrypsinFecal ElastaseLipase/amylase Fecal fatCT panc protocolMRCP +/- secretin?EUS +/- secretin or elastog?Elastography?Diffusion weighted MRI?TOUGHERCPSST (secretin and/or CCK)Biopsy (trucuts, open)
17. Why use PFTs?To STAGE patients with CPTo test for steatorrheaTo diagnose early CPTO EXCLUDE EARLY CP WHEN STRUCTURAL TESTS ARE EQUIVOVAL (DIRECT/TUBE ONLY)Complement to structural testsTo ensure steatorrhea is from the pancreas
18. Quick and “dirty” PFTsTrypsinFecal fatFecal elastaseFecal chymotrypsinOnly stage disease, don’t usually pick up early disease.
19. TrypsinRarely done wellRIA (I131) >>>> ELISA<20pg/dL, correlates well with pancr. Steator.20-29 Equivocal, often small duct.>30 NormalA great way to distinguish Gullo’s from APIf >150, very specific for APIn practice values >80 or so are suggestive of APToskes, NEJM, 1984
20. Fecal fatSpot6 or more dropletsOnly picks up extensive steatorrhea72hrMust be on 100g fat diet several days before>7grams/24hrs is steatorrheaVery nonspecificNoncompliance highWatch out for olestra/olein/orlistat/ezetimibe (zetia)
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22. Fecal ElastaseFalse positives if watery stool (20% of CP have SBBO)<100 correlates well with steatorrhea100-200 borderline decreased>200 normal“Not affected” by porcine enzymesMust use monoclonal ELISA
23. Fecal ElastaseIntermediate (100-200) values PROBLEMATIC!Better if <50 cutoff??May be affected by porcine enzymes (Schneider, Stein clin chem. 2005)21% of asympt/nonpanc control pts >60yr had fec elast’s <200, 6% <100: Herzig et al. BMC geriatr. 2011 Jan 25;11:4CCK and SST correl. better with 72 h FF than FE.Hahn, Lankisch, et al. Pancreas 2008 Apr;36(3):274-8FE has missed pts with calcific CP!Amann, Toskes et al Pancreas 1996 Oct;13(3):226-30.
24. Fecal chymotrypsinNo longer availableCould help with compliance with enzymesDetects porcine enzymes
25. Sensi/Speci of iPFTs1VS Histology. S. Freedman. NEJM. CP. June 1, 1995. and Kitagawa et al. Pancreas. 1997 Nov;15(4):402-8 2 Gullo L, Ventrucci M, Tomassetti P, Migliori M, Pezzilli R Dig Dis Sci. 1999 Jan;44(1):210-3.3Hahn, Lankish, Lowenfels et al. Pancreas. 2005 Mar;30(2):189-914Amann and Toskes. Pancreas. 1996 Oct;13(3):226-30.5Toskes. NEJM. June 1984.
26. Direct Function testsBackgroundS-MCRPSSTe-SSTS-EUSCCK-SST
27. Physiology: Bkgnd for function tests
28. MRCP vs S-MRCP
29. EsophagusStomachDUODENUMJEJUNUMGastric PortDuodenal PortoropharynxDreiling Tube, 26F
30. SST vs histologyHayakawa AJG 1992
31. TESTSensi (early)Sensi (late)Sensi (Combined)SpecificitySST75%197%190%190%1E-SST-----------94%295%2ERCP66%393%3-----90%3S-MRCP------92%669%490%4,6EUS---------------70%5 ,90%8, 60%979%5,85%8 ,72%9MRCP25%775%7-----90%7Trypsin10%1080-90%10-----95%101VS Histology. S. Freedman. NEJM. CP. June 1, 1995. and Kitagawa et al. Pancreas. 1997 Nov;15(4):402-8 2VS ERCP. D. Conwell, J Vargo et al. Clev Clinic.3VS SST. Forsmark and Chowdhury. Aliment. Pharm. Ther. 2003. 17. 7334VS fecal elastase/ERCP/Trig BT. ARJ Schneider. J Clin Gastro. Oct 2006. Vol 40 No 9. 5VS eSST. Stevens, Conwell. Dig Dis Sci. Oct 10, 20076VS ERCP. Monil. Am J Roetgen. 2004. 183. 12677VS ERCP. Sugiyama. J Gastro. 2007. 42. 108.8VS Histo. Non calcific CP, but all went on to surgery for CP. M. Eloubeidi. Gastroint Endo. Sept 07. 5019VS eSST. D. Conwell. Dig Dis Sci. 2007. 52: 1206.10Toskes. NEJM. June 1984. Sensitivity/Specificity for CP
32. E-SSTProbably about as good as SSTDirect RCT still used sedation for SST tooOccupies EGD room for one hour45 minute collection only a few % less sens as 60 minuteRecent study by Conwell showed CCK stim may be more sensi (not true in past)More cumbersome.
33. S-EUSCombined EUS plus SSTBetter coding for SSTEUS may add something to SSTSee panc duct directly and after secretinToo much sedation needed?Does the operator get overloaded?Is all the bicarbonate collected?
34. EUS3-5 of: (3: Romagnuolo, GIE 2007, Raimondo and Conwell, 4-5)Foci, Strands, Lobularity (w/ w/o honeycombing) Hyperechoic duct walls, Visible side branches, Main PD dil (3,2,1mm), Calcific, CystsRosemont (GIE June 2009, Catalano, et al)Major criteria: (1) hyperechoic foci with shadowing and main pancreatic duct (PD) calculi and (2) lobularity with honeycombing. Minor criteria: cysts, dilated ducts > or =3.5 mm, irregular PD contour, dilated side branches > or =1 mm, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules
35. EUS: problemsSame as ERCP/MRCP/SST: DM, age, AP, prior modest ETOH, give subtle changes in absence of clinical chronic pancLots of inter and intraobserver variabilityChange in “gain” can have big impactLack of gold std (all post surgery, masses/cys)Small studies when compared to histo/SSTLieb, Farrell, Savides, Leblanc, Forsmark, Draganov, Wagh, submitted 2010
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38. SST-CCKCombined secretin and cholecystokinin StimulationNo better than SST aloneBut what about in CFTR mutations?
39. New HorizonsDiffusion weighted MRI with secretinEUS elastographyMR elastographyC14 bicarb breath testSecretin-PET
40. Diffusion weighted (DWI) MRI with secretinDWI measures sum of random motions of protonsLower values or delayed peak in chronic panc, esp with secretinIU says secretin not help, St. Louis U/Turkey says it does (1.5Tesla vs 3 Tesla?).Can also better distinuish AP from CANCERSmall insulinomas being detected.
41. EUS elastographyMeasure of tissue stiffness also uses sound waves to detect reverberations.Uses hitachi attachmnt to pentax linear EUS.Santiago de Compostella, Spain; France; Japan; GermanyA 2007 study showed was only 60% sensitive in detecting CP vs normal but in 2008 in GIE, a Danish group used neural network processing for quantitative rather than qualitative analysis and much improved—but analysis occurs after procedure.
42. Iglesias-Garcia, GIE Dec 2009
43. Magnetic Resonance ElastographyYin M, Chen J, Glaser KJ, Talwalkar JA, Ehman RL. Abdominal magnetic resonance elastography. Top Magn Reson Imaging. 2009 Apr;20(2):79-87.Better known for liver, but also works for pancreas/spleen.
44. Cases 29 yo female with two prior attacks of gallstone pancreatitis, s/p chole, now with chronic abd pain, normal CT/MRI/EGD/gastric emptying test, sounds like pancreas and EUS with 4minor criteria. What is your next test?
45. Case54 yo male former alcoholic (quit 8 yr) with history of acute pancreatitis in ICU 2 weeks 3 years ago. Still with chronic abd pain. CT with mild atrophy. EGD/GES neg. What is your next test and why?
46. Case65 yo female with chronic crampy abd pain and diarrhea. EGD/colo neg. CT with calcific CP (idiopathic). No duct dil. What is your next test?
47. Case con’tSpot fecal fat is positiveNext test if any?
48. Case55 yo diabetic female with crampy abd pain, mild weight loss, loose stools, spots of oil in bowl, hard to flush. CT scan, EGD/ colonosc, celiac labs neg.Fecal elastase 80What is your diagnosis and next step?
49. Take Home PointsKnow how to define CP, “irreversible“ damageEtiologies of CPLevel I Evidence in CP is rare—underfundingCP pts lie on a spectrum from minimal change to obvious disease. (stage)Do not eliminate the possiblity of early CP too early in diff dxMake a correct diagnosis. Interpret early stage disease with caution esp EUS/ERCP
50. Take Home Points Con’tDirect Function testing more accurate for early dzKnow strengths and weakness of the secretin stimulation test, S-MRCP, fecal elastase, EUSEasy tests (indirect PFT) like trypsin, fecal elastase are better at staging disease than at descriminating early CP from normal.New tests: diffMRI, S-MRCP, EUS-elastogr