Pancreatic Function Testing
John G.Lieb II MD
Assistant Professor of Clinical Medicine
6/27/2014
Golden Rule
• Eat when you can
• Sleep when you can and…
• Don’t touch the pancreas!
– House of God
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
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.
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
Etiology of CP
ALCOHOL &
TOBACCO
Obstructive
IDIOPATHIC
Autoimmune
HEREDITARY
METABOLIC
Tropical
Lieb and Toskes, Hosp Phys. Brd Rvw 2007
Chronic Pancreatitis: the Spectrum
% Damage
30%
Damage
Starts
60%
80-90%
Structural damage
PAIN
Diabetes
(Pos CT/EUS/ERCP)
“Minimal ∆”
“Small Duct”
Steatorrhea
“BIG DUCT”
(pos secretin)
CANCER RISK
Pain may dec
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. 2006 Mar 9;7(2):241-2;
Consequences of Chronic Panc
•
•
•
•
•
•
Pain
Steatorrhea
Diabetes
Biliary obs
B12 def
Cancer
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
Steatorrhea/Exocrine Insufficiency
• Happens at 90% destruction of pancreas
– Nonlinear, cliff
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
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
Diagnosis of CP
Structural Tests
• CT
• MRI/MRCP
• EUS
Function Tests
• Fecal fat
• Serum Trypsin
• Fecal Elastase
• Glucose/GTT
• Panc.Polypeptide
• S-MRCP
• S-EUS
• SST
• E-SST
Pancreatic Function Tests (PFTs)
Indirect (often tubeless)
•
•
•
•
•
Fecal fat
Trypsin
Glucose/GGT
Panc.polypeptide
Dual Label Schilling test
Direct
• S-MRCP
• S-EUS
• eSST
• SST
• CCK/SST
• Bentiromide test (historical)
• Lundh test (Europe)
Tests to Diagnose CP
EASY ON PTS
TOUGH
•
•
•
•
•
•
•
•
•
• ERCP
• SST (secretin and/or CCK)
• Biopsy (trucuts, open)
Trypsin
Fecal Elastase
Lipase/amylase
Fecal fat
CT panc protocol
MRCP +/- secretin?
EUS +/- secretin or elastog?
Elastography?
Diffusion weighted MRI?
Why use PFTs?
• To STAGE patients with 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
Quick and “dirty” PFTs
•
•
•
•
•
Trypsin
Fecal fat
Fecal elastase
Fecal chymotrypsin
Only stage disease, don’t usually pick up
early disease.
Trypsin
•
•
•
•
•
•
•
•
Rarely done well
RIA (I131) >>>> ELISA
<20pg/dL, correlates well with pancr. Steator.
20-29 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
Fecal fat
• Spot
– 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)
Fecal Elastase
• False positives if watery stool (20% of CP have
SBBO)
• <100 correlates well with steatorrhea
• 100-200 borderline decreased
• >200 normal
• “Not affected” by porcine enzymes
• Must use monoclonal ELISA
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. 2011 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):226-30.
Fecal chymotrypsin
• No longer available
• Could help with compliance with enzymes
– Detects porcine enzymes
Sensi/Speci of iPFTs
1VS 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):189-91
4Amann and Toskes. Pancreas. 1996 Oct;13(3):226-30.
5Toskes. NEJM. June 1984.
Direct Function tests
•
•
•
•
•
•
Background
S-MCRP
SST
e-SST
S-EUS
CCK-SST
Physiology: Bkgnd for function tests
MRCP vs S-MRCP
oropharynx
Dreiling Tube,
26F
Duodenal
Port
Esophagus
Gastric
Port
Stomach
DUODENUM
JEJUNUM
SST vs histology
H isto lo g y
N
P ea k H C O 3
N o rm al
54
9 1 .7
E q u iv o cal
15
8 4 .5
M ild
10
7 0 .2
M o d erate
9
6 3 .4
S ev ere
20
5 0 .5
Hayakawa AJG 1992
Sensitivity/Specificity for CP
TEST
SST
E-SST
ERCP
Sensi (early) Sensi (late) Sensi (Combined) Specificity
75%1
-----66%3
S-MRCP -----EUS
------MRCP
25%7
Trypsin
1VS
10%10
97%1
----93%3
90%1
94%2
-----
90%1
95%2
90%3
92%6
-------75%7
69%4
90%4,6
70%5 ,90%8, 60%9 79%5,85%8 ,72%9
-----
80-90%10 -----
90%7
95%10
Histology. S. Freedman. NEJM. CP. June 1, 1995. and Kitagawa et al. Pancreas. 1997
Nov;15(4):402-8
2VS
3VS
ERCP. D. Conwell, J Vargo et al. Clev Clinic.
SST. Forsmark and Chowdhury. Aliment. Pharm. Ther. 2003. 17. 733
4VS 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, 2007
6VS ERCP. Monil. Am J Roetgen. 2004. 183. 1267
7VS 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.
501
9VS eSST. D. Conwell. Dig Dis Sci. 2007. 52: 1206.
10
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.
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?
• 3-5 of:
EUS
– (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
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
SST-CCK
• Combined secretin and cholecystokinin
Stimulation
• No better than SST alone
– But what about in CFTR mutations?
New Horizons
•
•
•
•
•
Diffusion weighted MRI with secretin
EUS elastography
MR elastography
C14 bicarb breath test
Secretin-PET
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.
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.
Iglesias-Garcia, GIE Dec 2009
Magnetic Resonance Elastography
• Yin 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.
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?
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?
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?
Case con’t
• Spot fecal fat is positive
• Next test if any?
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?
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
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