1. Pancreatic Function Testing
John G.Lieb II MD
Assistant Professor of Clinical Medicine
6/27/2014

2. Don’t touch the pancreas!
Golden Rule
Eat when you can
Sleep when you can and…
Don’t touch the pancreas!
House of God

3. Outline Chronic Pancreatitis def, epidemiol, causes
Spectrum of chronic pancreatitis
When does steatorrhea occur, why, how, so what?
Panc funct tests vs other tests for chronic panc
Stool/indirect Panc function tests
Direct (often tube) panc function tests
Future Panc function tests
Cases

4. A Few Key Pearls for Chronic Pancreatitis
What 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” damage
Histologic 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 strictures
The first three dogma being challenged
Pain or steatorrhea not necessary

6. Etiology of CP ALCOHOL & TOBACCO IDIOPATHIC HEREDITARY
Lieb and Toskes, Hosp Phys. Brd Rvw 2007

8. Make the Correct Diagnosis
Chronically elevated amy/lip do not CP make
Gullo’s1, vomitting, opiates
In early CP, imaging and labs may be negative or equivocal
Avoid labelling as CP
Avoid sick role, pyschosocialeconomic consequen.
Much acute relapsing pancreatitis is actually early chronic pancreatitis
Gullo L. JOP Mar 9;7(2):241-2;

9. Consequences of Chronic Panc
Pain
Steatorrhea
Diabetes
Biliary obs
B12 def
Cancer

10. Is Steatorrhea Present?
Consequences are significant
Treatment is chronic and expensive
3-5$/enzyme pill
Insurance co’s may require proof
Now you have proven advanced chronic panc

11. Steatorrhea/Exocrine Insufficiency
Happens at 90% destruction of pancreas
Nonlinear, cliff

12. Consequences of Steatorrhea
Weight loss/underweight
Vit A, D, K, E, B12 deficiencies
Magnesium deficiency
Osteoporosis
Low HDL
Higher mortality in CP patients. From this?
Oxalate renal stones

13. Is the Steatorrhea from the Pancreas?
Non pancreatic steatorrhea quite common
Many pancreas patients have coexisting small bowel bacterial overgrowth or even sprue
Autoimmune CP patients often have IBD

14. Diagnosis of CP Structural Tests Function Tests CT MRI/MRCP EUS
Fecal fat
Serum Trypsin
Fecal Elastase
Glucose/GTT
Panc.Polypeptide
S-MRCP
S-EUS
SST
E-SST

15. Pancreatic Function Tests (PFTs)
Indirect (often tubeless)
Direct
Fecal fat
Trypsin
Glucose/GGT
Panc.polypeptide
Dual Label Schilling test
S-MRCP
S-EUS
eSST
SST
CCK/SST
Bentiromide test (historical)
Lundh test (Europe)

16. Tests to Diagnose CP EASY ON PTS TOUGH Trypsin Fecal Elastase
Lipase/amylase
Fecal fat
CT panc protocol
MRCP +/- secretin?
EUS +/- secretin or elastog?
Elastography?
Diffusion weighted MRI?
ERCP
SST (secretin and/or CCK)
Biopsy (trucuts, open)

17. Why use PFTs? To STAGE patients with CP To diagnose early CP
To test for steatorrhea
To diagnose early CP
TO EXCLUDE EARLY CP WHEN STRUCTURAL TESTS ARE EQUIVOVAL (DIRECT/TUBE ONLY)
Complement to structural tests
To ensure steatorrhea is from the pancreas

18. Quick and “dirty” PFTs Trypsin Fecal fat Fecal elastase
Fecal chymotrypsin
Only stage disease, don’t usually pick up early disease.

19. Trypsin Rarely done well RIA (I131) >>>> ELISA
<20pg/dL, correlates well with pancr. Steator.
Equivocal, often small duct.
>30 Normal
A great way to distinguish Gullo’s from AP
If >150, very specific for AP
In practice values >80 or so are suggestive of AP
Toskes, NEJM, 1984

20. Fecal fat Spot 72hr 6 or more droplets
Only picks up extensive steatorrhea
72hr
Must be on 100g fat diet several days before
>7grams/24hrs is steatorrhea
Very nonspecific
Noncompliance high
Watch out for olestra/olein/orlistat/ezetimibe (zetia)

22. Fecal Elastase False positives if watery stool (20% of CP have SBBO)
<100 correlates well with steatorrhea
borderline decreased
>200 normal
“Not affected” by porcine enzymes
Must use monoclonal ELISA

23. Fecal Elastase Intermediate (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 Jan 25;11:4
CCK and SST correl. better with 72 h FF than FE.
Hahn, Lankisch, et al. Pancreas 2008 Apr;36(3):274-8
FE has missed pts with calcific CP!
Amann, Toskes et al Pancreas 1996 Oct;13(3):

24. Fecal chymotrypsin No longer available
Could help with compliance with enzymes
Detects porcine enzymes

25. Sensi/Speci of iPFTs
1VS Histology. S. Freedman. NEJM. CP. June 1, and Kitagawa et al. Pancreas Nov;15(4):402-8
2 Gullo L, Ventrucci M, Tomassetti P, Migliori M, Pezzilli R Dig Dis Sci Jan;44(1):210-3.
3Hahn, Lankish, Lowenfels et al. Pancreas Mar;30(2):189-91
4Amann and Toskes. Pancreas Oct;13(3):
5Toskes. NEJM. June 1984.

26. Direct Function tests
Background
S-MCRP
SST
e-SST
S-EUS
CCK-SST

27. Physiology: Bkgnd for function tests

28. MRCP vs S-MRCP

29. Dreiling Tube, 26F DUODENUM JEJUNUM oropharynx Duodenal Port Esophagus
Gastric Port
Stomach
DUODENUM
JEJUNUM

30. SST vs histology
Hayakawa AJG 1992

31. Sensitivity/Specificity for CP
TEST
Sensi (early)
Sensi (late)
Sensi (Combined)
Specificity
SST
75%1
97%1
90%1
E-SST
------
-----
94%2
95%2
ERCP
66%3
93%3
90%3
S-MRCP
92%6
69%4
90%4,6
EUS
70%5 ,90%8, 60%9
79%5,85%8 ,72%9
MRCP
25%7
75%7
90%7
Trypsin
10%10
80-90%10
95%10
1VS Histology. S. Freedman. NEJM. CP. June 1, 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
4VS fecal elastase/ERCP/Trig BT. ARJ Schneider. J Clin Gastro. Oct Vol 40 No 9.
5VS eSST. Stevens, Conwell. Dig Dis Sci. Oct 10, 2007
6VS ERCP. Monil. Am J Roetgen
7VS ERCP. Sugiyama. J Gastro
8VS Histo. Non calcific CP, but all went on to surgery for CP. M. Eloubeidi. Gastroint Endo. Sept 07.
501
9VS eSST. D. Conwell. Dig Dis Sci : 1206.
10Toskes. NEJM. June 1984.

32. E-SST Probably about as good as SST
Direct RCT still used sedation for SST too
Occupies EGD room for one hour
45 minute collection only a few % less sens as 60 minute
Recent study by Conwell showed CCK stim may be more sensi (not true in past)
More cumbersome.

33. S-EUS Combined EUS plus SST Better coding for SST
EUS may add something to SST
See panc duct directly and after secretin
Too much sedation needed?
Does the operator get overloaded?
Is all the bicarbonate collected?

34. EUS 3-5 of: Rosemont (GIE June 2009, Catalano, et al)
(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, Cysts
Rosemont (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: problems
Same as ERCP/MRCP/SST: DM, age, AP, prior modest ETOH, give subtle changes in absence of clinical chronic panc
Lots of inter and intraobserver variability
Change in “gain” can have big impact
Lack of gold std (all post surgery, masses/cys)
Small studies when compared to histo/SST
Lieb, Farrell, Savides, Leblanc, Forsmark, Draganov, Wagh, submitted 2010

38. SST-CCK Combined secretin and cholecystokinin Stimulation
No better than SST alone
But what about in CFTR mutations?

39. New Horizons Diffusion weighted MRI with secretin EUS elastography
MR elastography
C14 bicarb breath test
Secretin-PET

40. Diffusion weighted (DWI) MRI with secretin
DWI measures sum of random motions of protons
Lower values or delayed peak in chronic panc, esp with secretin
IU says secretin not help, St. Louis U/Turkey says it does (1.5Tesla vs 3 Tesla?).
Can also better distinuish AP from CANCER
Small insulinomas being detected.

41. EUS elastography
Measure of tissue stiffness also uses sound waves to detect reverberations.
Uses hitachi attachmnt to pentax linear EUS.
Santiago de Compostella, Spain; France; Japan; Germany
A 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 Elastography
Yin M, Chen J, Glaser KJ, Talwalkar JA, Ehman RL. Abdominal magnetic resonance elastography. Top Magn Reson Imaging 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. Case
54 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. Case
65 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’t
Spot fecal fat is positive
Next test if any?

48. Case
55 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 80
What is your diagnosis and next step?

49. Take Home Points
Know how to define CP, “irreversible“ damage
Etiologies of CP
Level I Evidence in CP is rare—underfunding
CP pts lie on a spectrum from minimal change to obvious disease. (stage)
Do not eliminate the possiblity of early CP too early in diff dx
Make a correct diagnosis.
Interpret early stage disease with caution esp EUS/ERCP

50. Take Home Points Con’t
Direct Function testing more accurate for early dz
Know strengths and weakness of the secretin stimulation test, S-MRCP, fecal elastase, EUS
Easy 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