Sabato 20 Giugno 2015
Elastasi Fecale
Wirsungrafia con Secretina
Luca Frulloni
Dept of Medicine
Pancreas Center
University of Verona – Italy
Elastasi Fecale e MR con Secretina (sMRCP)
Applicazioni Diagnostiche
Elastasi Fecale
sMRCP
Test di
Funzione Esocrina
Pancreatica Diretto
Valutazione
ghiandolare
Valutazione
Sistema Duttale
Pancreatico
Test di Funzione Esocrina Pancreatica
Metodologia – Torgiano “Docet”
Test
Accuratezza
del test
Diagnosi
Probabilità
pre-test
Probabilità
post-test
Diagnosi di Pancreatite Autoimmune con sIgG4
in Presenza di Massa Pancreatica
Sensitivity
LR =
1-Specificity
Probabilità
AIP
IgG4
sensitivity =70% (0.7)
specificity = 95% (0.95)
--
+ malattia
autoimmune
0.7
LR per IgG4 =
= 14
0.05
Nomogramma di Fagan
Insufficienza Pancreatica Esocrina
Validità del Test di Funzione Vs. Popolazione Selezionata
Popolazione
selezionata
Prevalenza
Stimata
Sospetto Clinico
IPE
Test Diagnostici
Funzione Esocrina Pancreatica
Possibili Scenari Clinici
Prevalenza
Pancreatite cronica
Medio-Alta
Pancreatite ricorrente
Bassa
Neoplasie pancreatiche
Media
Post-chirurgia pancreatica
Altro
(i.e. diabete, fibrosi cistica,
dispepsia, diarrea, …)
Alta
Bassa
Funzione Esocrina Pancreatica
Ruolo di un Test Diagnostico nella Pratica Clinica
Diagnosticare una pancreatite cronica
Valutare la funzione esocrina pancreatica
- al momento del dosaggio
- nel tempo
Decidere se è necessaria una terapia sostitutiva
Pancreatic Exocrine Function
Fecal Elastase Test
1. .Non invasive, tubeless
2. .Pancreas-specific human protease
3. .Minimal changes during intestinal transit
4. .Stable (not degraded)
5. .Readily measured in stool samples
6. .Unaffected by pancreatic enzyme replacement therapy
7. .Inexpensive
Funzione Esocrina Pancreatica
Ruolo di un Test Diagnostico nella Pratica Clinica
Diagnosticare una pancreatite cronica
Valutare la funzione esocrina pancreatica
- al momento del dosaggio
- nel tempo
Decidere se è necessaria una terapia sostitutiva
Fecal Elastase test
Proposed Classification of Pancreatic Exocrine Insufficiency
normal
500 g/g
mild
insufficiency
200 g/g
severe
insufficiency
100 g/g
Author (Ref)
Comparative Groups
Comparison
Sensitivity
Specificity
Ammann (13)
HC, Malabsorption
S-P test, ERCP
surgery
100% (severe)
43% (mild-mod)
29%
Dominguez-Munoz (14)
Non pancreatic
diseases
ERCP, US, CT
100% (severe)
0% (mild-mod)
83%
Gullo (15)
Non pancreatic
diseases, HC
ERCP, US, clinic
77% (overall)
91.4 (mod-severe)
95.8%
Hardt (4)
No CP
ERCP
45.3 (overall)
57.4% (mod-severe)
75%
Lankish (16)
CP Non EPI
S-P test
53% (overall)
85% (severe)
100%
Leodolter (17)
No CP
ERCP, US, CT
50% (overall)
85% (severe)
100%
Loser (5)
GI diseases
S-C test
92% (overall)
100% (severe)
90%
Luth (3)
CP Non EPI
S-C test
84% (overall)
60% (severe)
78%
Stein (18)
CF
S-P test
96% (overall)
94%
Walkowiak (19)
No GI diseases
S-C test
89% (overall)
100% (severe)
96.4%
HC= healthy control CF=cystic fibrosis
S-P= secretin-pancreozymin S-C= secretin cerulein
EPI=pancreatic exocine insufficiency
Rothenbacher D et al, Scand J Gastroenterol, 2005; 40:697-704
Author (Ref)
Comparative Groups
Comparison
Sensitivity
Specificity
Ammann (13)
HC, Malabsorption
S-P test, ERCP
surgery
100% (severe)
43% (mild-mod)
29%
Dominguez-Munoz (14)
Non pancreatic
diseases
ERCP, US, CT
100% (severe)
0% (mild-mod)
83%
Gullo (15)
Non pancreatic
diseases, HC
ERCP, US, clinic
77% (overall)
91.4 (mod-severe)
95.8%
Hardt (4)
No CP
ERCP
45.3 (overall)
57.4% (mod-severe)
75%
Lankish (16)
CP Non EPI
S-P test
53% (overall)
85% (severe)
100%
Leodolter (17)
No CP
ERCP, US, CT
50% (overall)
85% (severe)
100%
Loser (5)
GI diseases
S-C test
92% (overall)
100% (severe)
90%
Luth (3)
CP Non EPI
S-C test
84% (overall)
60% (severe)
78%
Stein (18)
CF
S-P test
96% (overall)
94%
Walkowiak (19)
No GI diseases
S-C test
89% (overall)
100% (severe)
96.4%
HC= healthy control CF=cystic fibrosis
S-P= secretin-pancreozymin S-C= secretin cerulein
EPI=pancreatic exocine insufficiency
Rothenbacher D et al, Scand J Gastroenterol, 2005; 40:697-704
Funzione Esocrina Pancreatica
Ruolo di un Test Diagnostico nella Pratica Clinica
Diagnosticare una pancreatite cronica
Valutare la funzione esocrina pancreatica
- al momento del dosaggio
- nel tempo
Decidere se è necessaria una terapia sostitutiva
Fecal Elastase test
How evaluate it?
500 g/g
100%
<1 g/g
0%
mild
insufficiency
200 g/g
severe
insufficiency
100 g/g
Residual pancreatic function
normal
500 g/g
Fecal Elastase 1 “over the time”
Initial Diagnosis of Recurrent Pancreatitis
Final Diagnosis
Recurrent
Pancreatitis
Chronic
Pancreatitis
Funzione Esocrina Pancreatica
Ruolo di un Test Diagnostico nella Pratica Clinica
Diagnosticare una pancreatite cronica
Valutare la funzione esocrina pancreatica
- al momento del dosaggio
- nel tempo
Decidere se è necessaria una terapia sostitutiva
Impairment of Pancreatic Exocrine Function
The Problem of Definition
Terms used to identify patients who need treatment:
pancreatic exocrine insufficiency
maldigestion
steatorrhea
malnutrition
However, pancreatic exocrine insufficiency and a
subsequent maldigestion are present in some degree in all
patients suffering from chronic pancreatitis.
Impairment of Pancreatic Exocrine Function
Which patients need to be treated?
Residual pancreatic function
100%
maldigestion
10%
steatorrhea (overt, by FF output)
malnutrition (overt)
0%
Chronic Pancreatitis
Guidelines
China1
Type
Year
Indication for PERT
EL
RG
GL
2005
steatorrhea
–
–
2010
steatorrhea
1a
A
1b
A
2b
B
no methodology
Italian2
GL
weight loss
or symptoms of malabsorption
German3
GL
2012
steatorrhea (>15 g/24 h)
steatorrhea (7-15 g/24 h)
+ weight loss
or symptoms of malabsorption
Spanish4
GL
2013
steatorrhea (>15 g/24 h)
malabsorption or malnutrition
1 Chin
J Dig Dis, 2005; 6; 198-201
Liv Dis, 2010; 42 (suppl.1); S381-S406
3 Z Gastroenterol , 2012; 50: 1176-1224
4 Pancreatology , 2013: 13: 18-28
2 Dig
Impairment of PEI and Fecal Elastase
Clinical Questions
Is FE correlated with steathorrea?
Can FE identify patients with
non overt steatorrhea?
Author (Ref)
Comparative Group
Comparison
Sensitivity
Specificity
Ammann (13)
HC, Malabsorption
S-P test, ERCP
surgery
100% (severe)
43% (mild-mod)
29%
Dominguez-Munoz (14)
Non pancreatic
diseases
ERCP, US, CT
100% (severe)
0% (mild-mod)
83%
Gullo (15)
Non pancreatic
diseases, HC
ERCP, US, clinic
77% (overall)
91.4 (mod-severe)
95.8%
Hardt (4)
No CP
ERCP
45.3 (overall)
57.4% (mod-severe)
75%
Lankish (16)
CP Non EPI
S-P test
53% (overall)
85% (severe)
100%
Leodolter (17)
No CP
ERCP, US, CT
50% (overall)
85% (severe)
100%
Loser (5)
GI diseases
S-C test
92% (overall)
100% (severe)
90%
Luth (3)
CP Non EPI
S-C test
84% (overall)
60% (severe)
78%
Stein (18)
CF
S-P test
96% (overall)
94%
Walkowiak (19)
No GI diseases
S-C test
89% (overall)
100% (severe)
96.4%
HC= healthy control CF=cystic fibrosis
S-P= secretin-pancreozymin S-C= secretin cerulein
EPI=pancreatic exocine insufficiency
Rothenbacher D et al, Scand J Gastroenterol, 2005; 40:697-704
Pancreatic Exocrine Function in Chronic Pancreatitis
Correlation between FE and Fecal Fat Output
Benini L et al, Pancreatol, 2013; 34(2): 202-7
Pancreatic Exocrine Function in Chronic Pancreatitis
Correlation between FE and Fecal Fat Output
Benini L et al, Pancreatol, 2013; 34(2): 202-7
Pancreatic Exocrine Function in Cystic Fibrosis
FE Cut-off to Identify Patients with Steatorrhea
7 g/24 h
Walkowiak J et al, Scand J Gastroenterol, 1999; 34(2): 202-7
Pancreatic Exocrine Function in Chronic Pancreatitis
Correlation between FE and Steathorrea in NON operated patients
Fecal elastase extremely reduced
<10% normal value1
Normal value
500 g/g stools
Steatorrhea
10% of normal value
50 g/g stools
Di Magno E et al, N Engl J Med, 1973; 288: 813-5
Pancreatic Exocrine Function in Chronic Pancreatitis
Correlation between FE and Fecal Fat Output
Benini L et al, Pancreatol, 2013; 34(2): 202-7
Funzione Esocrina Pancreatica
Sincronia per una Corretta Digestione
Regolazione ormonale
CCK e Secretina
Svuotamento
Gastrico
Secrezione
Biliare
Lume
Duodenale
Secrezione
Pancreatica
Type of Pancreatic Surgery
Implications on Enteral Mixing
Whipple
Pyloro-Preserving
Puestow
pancreatic head resection
pancreatic head resection
pancreato-jejunostomy
Asynchrony among Biliary and Pancreatic Secretions and Chyme
Pancreatic Exocrine Function in Chronic Pancreatitis
FE Cut-off to Identify Patients with Steatorrhea
14 out of 19
74%
ONLY
in operated
patient
“…., the value of FE-1 at which we expect a 24 h fecal fat output of 7 g (the upper limit of
the normal range) is derived as 14 g/g in non-operated patients and as high as 207 g/g in
operated patients.”
Benini L et al, Pancreatol, 2013; 34(2): 202-7
Impairment of Pancreatic Exocrine Function
Which patients need to be treated?
Residual pancreatic function
100%
maldigestion
Is mild-moderate PEI clinical relevant?
Does correction of mild-moderate PEI
improve outcome?
10%
Steatorrhea (overt,  FF output)
Malnutrition (overt)
0%
Chronic Pancreatitis
Fecal Elastase Vs Vitamin D Levels
Mann STW et al, Dig Dis Sci, 2003; 48(3): 533-538
MR/MRCP Imaging
Problem Solving Tool
Non invasive
No radiations
Very rare adverse events after contrast medium injection
High contrast resolution
Investigation of biliary tree and pancreatic ductal system
Secretin stimulation
Pancreatic exocrine function evaluation after secretin stimulation
MR/MRCP Imaging
Problem Solving Tool
Non invasive
No radiation
Very rare adverse event after contrast medium injection
High contrast resolution
Investigation of biliary tree and pancreatic ductal system
Secretin stimulation
Pancreatic exocrine function evaluation after secretin stimulation
Secretin Stimulation
Physiology
Increase of fluids/bicarbonates
pancreatic secretion
Filling of pancreatic duct system
Modifications of
Sphincter of Oddi motility
Sphincter of Oddi
Manometric Findings in Healthy Subjects
basal pressure
phasic
wave
Jeneen GE et al, Gastroenterology, 1980; 78: 317-324
Sphincter of Oddi
Manometric Findings after Secretin Stimulation in Healthy Subjects
p<0.05
p<0.05
p<0.05
Frequency (N. phasic waves/min)
p<0.05
Secretin i.v.
1 UI/kg
Jeneen GE et al, Gastroenterology, 1980; 78: 317-324
Secretin Stimulation
Consequences
early phase
1-3 min
Main Pancreatic Duct
 fluids/bicarbonates
secretion
 SO contractions amplitude
 SO contractions frequency
SO MORE CLOSED
Dilation
late phase
3-10 min
Secretin
administration
 fluids/bicarbonates
secretion
 SO contractions amplitude
 SO contractions frequency
SO OPEN
Return to baseline value
Duodenal lumen filling
SO=sphincter of Oddi
MRCP after Secretin Stimulation (sMRCP)
Normal Findings
basal
7 min
3 min
10 min
sMRCP in Chronic Pancreatitis
Not Suggested when MPD Markedly Dilated (Advanced Stage)
sMRCP Function Test
Duodenal Filling
at 10 min after S
Grade 1 limited at duodenal bulb
severe insufficiency
basal
4 min
Grade 2 up to genu inferior
moderate insufficiency
Grade 3 beyond genu inferior
normal
6 min
10 min
Cappelliez O et al T et al, Radiology, 2000; 215: 358–364
sMRCP
Patient with Relapsing Pancreatitis
Persistent dilation of Wirsung duct at 10 min
Suspicion for Sphincter of Oddi Dysfunction
sMRCP Function Test
Comparison with Intraductal Secretin Test
Cappelliez O et al T et al, Radiology, 2000; 215: 358–364
R=0.573
p<0.001
Manfredi R et al., Radiol Med, 2012; 117(2); 282-292.
sMRCP in Chronic Pancreatitis
Cost
- MRI/MRCP = 300 €/400 $ (refund by Veneto Region)
- Secretin = 160 €/212 $ (in Verona Hospital)
- Time to perform sMRCP = 15-20 min longer than MRI/MRCP (30 min)
MR in Chronic Pancreatitis
Applications
Standard
MRCP
sMRCP
DWI
Hansen TM et al., World J Gastroenterol, 2013; 19(42): 7241-7246
Hansen TM et al., World J Gastroenterol, 2013; 19(42): 7241-7246
Elastasi Fecale – MRCP con secretina
Take Home Messages
1. Elastasi fecale = unico test di funzione esocrina pancreatica
disponibile
2. Nei pazienti con pancreatite (acuta, ricorrente, cronica)
3. La riduzione di elastasi fecale nel tempo è indice di una
cronicizzazione
4. La MR Addome è un esame completo, morfologico e funzionale
5. L’indicazione all’esecuzione di MR addome va attentamente
valutata poiché costoso