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100% (severe)
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