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Diagnosing of pancreatic exocrine insufficiency clinical and paraclinical approach
Matthias Löhr
Professor of Gastroenterology & Hepatology
Gastrocentrum
Karolinska University Hospital
Ätiologie Pathologie Pathophysiologie
Exokrine & endokrine Pankreasinsuffizienz
Epidemiologie Symptome Diagnose
laborchemisch Diagnostik
Pankreasfunktionstests Bildgebung Therapie
©M. Löhr 2013
What the pancreas does!
©M. Löhr 2013
Maldigestion because of
inadequate pancreatic enzyme activity
due to either - insufficient enzyme production - insufficient enzyme activation - early enzyme degradation
Matthias Löhr Löhr, Exocrine Pancreas Insufficiency, Uni•Med, 2010
Pancreatic Exocrine Insufficiency Definition
©M. Löhr 2013
Primary problem is in the pancreas - destruction - innervation
Secondary enzymes are released but do not work - anatomical changes - dysregulated activation - dysregulated inactivation
Matthias Löhr
Pancreatic Exocrine Insufficiency (PEI) Classification
Löhr, Exocrine Pancreas Insufficiency, Uni•Med, 2010
©M. Löhr 2013 Matthias Löhr
Maldigestion 2° to pancreatic enzyme deficiency!!
Deficiency of parenchyma • Chronic pancreatitis, cystic fibrosis, • Pancreatic cancer, S/P pancreatic resection Deficiency of secretion • Obstruction Papillary tumor • endogenous stimulation
Diabetes Mellitus • Inactivation
Zollinger Ellison Syndrome; Somatostatin-Tx
• Postcibal asynchronia
• S/P surgery • gastric/pancreatic
adapted from Keller & Layer, GUT 2005, 54 (Suppl. 6): vi9-29
1°
2°
©M. Löhr 2013
Matthias Löhr
WHO will develop pancreatic exocrine insufficiency?!!• Chronic pancreatitis
– alcoholic – hereditary – tropical – „idiopathic“ – autoimmune
• transient
• Diabetes mellitus
• Cystic fibrosis
• Rare metabolic defects – Schwachman-Diamond-Syndrome – (Co-) Lipase deficiency
• Pancreatic carcinoma patient
• Patient after (pancreatic) surgery – after gastric/duodenal/jejunal resection
1°
2°
Löhr, Exocrine Pancreas Insufficiency, Uni•Med, 2010
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab – Imaging – Function tests
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab – Imaging – Function tests
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Abdominal pain • Weight loss
• Digestive symptoms
– Diarrhea • Steatorrhea
– Flatulance – Bloating
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• WHO – m/f; old/young; family – Hx of gallstones/CCE
• WHEN did it start – Age at onset
• HOW – In conjunction with EtOH
• WHERE – Did the pain start
©M. Löhr 2013
• Presentation – A typical patient with
PEI has
• Abdominal pain • Loose bowel movements
– Diarrhea / Steatorrhea • Bloating • Flatulence
PEI – H & P!
NOT specific!
©M. Löhr 2013
How to diagnose PEI!
• Presentation – H & P
• Diagnostics
– Lab – Imaging – Function tests
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab – Imaging – Function tests
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab • Amylase & Lipase
”Elevated blood amylase has become a cornerstone in the diagnosis of [acute] pancreatitis.”
Elman et al., Arch Surg 1929;19:943-967
©M. Löhr 2013
Elevated pancreatic enzymes!
• Many causes • Even symptomatic
patients may have NO chronic pancreatitis
• In PEI, amylase and lipase could be below the LLN
Frulloni et al., JOP 2005, 6: 536-551
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab • Proalbumin • Mg, Zn • Vitamin 25-OH cholecalciferol • Retinol binding protein
Lindkvist et al.Pancreatology 2012, 12: 943-967 Löhr et al., uegj 2013, 1: 79-83
©M. Löhr 2013
How to diagnose PEI!
• Presentation – H & P
• Diagnostics
– Lab – Imaging – Function tests
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab – Imaging – Function tests
©M. Löhr 2013
Grade Enzymes Bicarbonate fecal fat Mild reduced normal normal Moderate reduced reduced normal Severe reduced reduced increased
Pancreatic function tests!
(acc to Lankisch, Dig Dis Sci, 1983)
Secretin-Pancreozymin-Test (SPT)!
©M. Löhr 2013
DiMagno & Layer in Go, The Pancreas from!DiMagno et al., NEJM 1977, 288: 854 and!DiMagno et al., Ann NY Acad Sci 1975, 252: 200!
Dynamics of PEI!
©M. Löhr 2013
Pancreatic function tests!
Test! mild PEI
moderate PEI
severe PEI
Evidence
Sensitivity (%) Sensitivity (%) Sensitivity (%) Specifity (%) f-Elastase-1 54% 75% 95% 85% (96% /
79%)$ 1a/b
Qualitative fat 0% 0% 78%§ 70%§ Chymotrypsin activity
<50% ca. 60% 80-90% 80-90% 1a/b
13C-breath tests (mixed Triglyceride)
62-100% 90-100% 80-90% 1b/2b
Siegmund & Löhr: Meta-analysis of pancreatic function tests. Z Gastroenterol 2004, 42: 1117-1128
• Pancreatic function testing may be used for the diagnosis of CP – Evidence 1c, recommendation B
• Secretin test (SPT) is the Gold Standard – Evidence 1b, recommendation A
• In clinical routine, non-invasive tests should be used
– Evidence 5, recommendation B – Fecal elastase-1 is widely available and can be used – The 13C breath test (MTG) is an alternative
©M. Löhr 2013
Diagnostic value of fecal elastase-1!• Test of choice
– Best of the available • Relatively speaking!
– Highly practicable
• Small amount of stool • Easy assay (ELISA)
– quick
– Reasonable cost/effort factor
25-83 % 33-100% 75-100%
Siegmund & Löhr: Meta-analysis of pancreatic function tests. Z Gastroenterol 2004, 42: 1117-1128
©M. Löhr 2013
Lipase vs. Elastase!
DiMagno & Layer in Go, The Pancreas from!DiMagno et al., NEJM 1977, 288: 854 and!DiMagno et al., Ann NY Acad Sci 1975, 252: 200! Benini et al., Pancreatology 2013, 13: 38-42!
©M. Löhr 2013
P. Hardt/M. Löhr: Use of FEC in PEI
0% 10% 20% 30% 40% 50% 60% 70% 80% 90%
100%
Sens
itivi
ty
mild moderate severe Control Fecal Elastase 1 Chymotrypsin [Löser et al. 1996]
Specificity Fecal elastase-1 comparison with SPT!
©M. Löhr 2013
Fecal elastase & degree of cP!
• Fecal elastase is – a good indicator of
severe chronic pancreatitis
• With significant EPI – A bad indicator of mild
and moderate chronic pancreatitis
Hardt et al., Pancreas 2002, 25: e6-e9
©M. Löhr 2013
Matthias Löhr
PEI in early chronic pancreatitis!• NO difference in FE-1 in patients with early cP
– You could throw a dice
Lankisch, Löhr et al., Gut 1998, 42: 551-554
©M. Löhr 2013
Fecal elastase-1 in CP!
• Disparity in operated vs. non-operated CP patients
• FE-1 < 15 = PEI?! – Low sens of fecal
fat
Benini et al., Pancreatology 2013, 13: 38-42!
©M. Löhr 2013
Matthias Löhr
Pseudo-PEI!• Diarrhea of non-pancreatic origin (IBS!) may mimic false-positive (i.e.
LOW ) fecal elastase-1 values => Lyophilisation of samples!
Fischer et al., SJG 2001
©M. Löhr 2013
Chronic pancreatitis - PEI!
• Presentation – H & P
• Diagnosis
– Lab – Imaging – Function tests
©M. Löhr 2013
Breath Test!
• Feed substrate with labeled C during stimulation meal
• Collect breath-out air in a bag
• Analyse in a MS or IR device
©M. Löhr 2013
Breath test!
©M. Löhr 2013
C13 Mixed-triglyceride breath test!
Domínguez-Munoz et al., CGH 2007, 5:484–488
©M. Löhr 2013
Changing concept of PEI!• PAST:
– Pancreatic exocrine insufficiency considered as an (isolated) organ defect
– Treatment of PEI guided by amelioration of symptoms
• Reversal of weight loss, bloating, steatorrhea
• TODAY: – Pancreatic exocrine insufficiency is
causing malnutrition – Treatment of PEI must look beyond
symptom control
Domínguez-Munoz et al., CGH 2007, 5:484–488
©M. Löhr 2013
Changing concept of PEI!
• The CONSEQUENCE of PEI is MALNUTRITION
©M. Löhr 2013
Vicious cycle of malnutrition!
• Vitamines o ADEK
• Minerals o Fe, Ca
• Trace elements o Mg, Zn, Mn Adapted from Best Practice & Research Clinical Gastroenterology 26 (2012) 663–675
©M. Löhr 2013 www.fightmalnutrion.eu
Vicious cycle of malnutrition!
©M. Löhr 2013
Malnutrition-InflammationComplex Syndrome (MICS)!
• In kidney disease a clear sequence of events has been described emerging from renal insufficiency to malnutrition
©M. Löhr 2013
• Malnutrition leads to deficits in micronutritients
• Lack of micronutritients leads to systemic inflammatory response (SIR)
Gorospe &Oxentenko, Best Practice 2012, 26: 663-675
©M. Löhr 2013 Merten, KliWo 1948, 26 (17/18): 261-262
©M. Löhr 2013
Evidence for malnutrition in PEI Vitamine Deficiencies"
cP CF β-carotine 89 % 90 % A 67 % 48 % E 71 % 70 % C 39 % 15 % B12 5 % 0 %
Löhr, Exocrine Pancreatic Insufficiency, Uni•Med 2010
©M. Löhr 2013
Vitamines & Trace Elements!
• Severe medical conditions as consequence of low vitamines, minerals, and trace elements
Gorospe & Oxentenko, Best Practice 2012, 26: 663-675
©M. Löhr 2013
Evidence for malnutrition in PEI Vitamine Deficiencies!
Sikkens et al., Pancreatology 2013, ePub
©M. Löhr 2013 Armstrong et al., Pancreatology 2007, 7: 37-44
Evidence for malnutrition in PEI Trace elements!
©M. Löhr 2013
Evidence for malnutrition in PEI Trace elements!
Armstrong et al., Pancreatology 2007, 7: 37-44
©M. Löhr 2013
©M. Löhr 2013
©M. Löhr 2013
Vitamins and SIR!
Duncan et al., Am J Clin Nutr 2012, 95: 64-71
©M. Löhr 2013
Vitamin D and Bone mineral density!
Sikkens et al., Pancreatology 2013, 13: 238-242
©M. Löhr 2013
Vitamin D and Bone mineral density!
Sikkens et al., Pancreatology 2013, 13: 238-242
©M. Löhr 2013
PEI & osteoporosis!
Duggan et al., Pancreas 2012; 41: 1119-1124
©M. Löhr 2013
PEI & osteoporosis!
Duggan et al., Pancreas 2012; 41: 1119-1124
©M. Löhr 2013
PEI & osteoporosis!• FE-1 correlates with
BMD • Low parameters of
bone metabolism
Haas & Löhr, submitted 2013
©M. Löhr 2013
What are the consequences!
• Measure malnutrition and not only the symptoms of PEI
• Treat malnutrition and not only the symptoms of PEI
©M. Löhr 2013
What are the consequences!
• Measure malnutrition and not only the symptoms of PEI
• Treat malnutrition and not only the symptoms of PEI
• Lack of interventional and long-term studies
Domínguez-Munoz et al., CGH 2007, 5:484–488
©M. Löhr 2013
How to measure malnutrition!• Clinical parameters
– BMI – Skin fold – Body impedance
• Laboratory parameters
– Vitamins • ADEK
– Trace elements – Key proteins
• RBP, (pre-) albumin
• Apparative – Body fat (CAT) – BMD – (EUS 4 PEI)
©M. Löhr 2013
How to improve diagnosing PEI!
www.e-p-c.org/hapaneu
©M. Löhr 2013
Bücher!
Thank you very much for your attention
