Transcript Chronic pancreatitis( Sanofi ) 2016

By
KHALED HEMIDA
‫عــن أبى هريرة رضى هللا عنــه أن‬
‫رســـول هللا صــلى هللا عليــه و سـلــم‬
‫قـــال ‪:‬‬
‫‪ ...‬و مــن ســـلك طــريقـــا يلتمــــس فيــه‬
‫عـلـمــــا ســهـــل هللا لـــه طـــر يقــــا الــى‬
‫الجنـــــة ‪.‬‬
‫رواه مســـــــلم‬
‫‪2‬‬
‫‪2004‬‬
Agenda
 Definition
 Epidemiology
 Pathogenesis
 Clinical presentation
 Complications
 Diagnosis
 Treatment
Pain in chronic pancreatitis could be improved
with all, except?
A)Antibiotics
b) Narcotics
c) Celiac block
e) Surgical drainage
f) Pancreatectomy
Definition
 Progressive inflammatory disease of the pancreas
characterized by irreversible structural changes can
resulting in irreversible exocrine and/ or endocrine
insufficiency
 Structural changes include:
– irregular sclerosis; focal or diffuse tissue destruction
– acinar cell +/or islet cell loss
– inflammatory cell infiltrates
– pancreatic duct abnormalities and obstruction
 Acute, recurrent acute, and CP thought as a disease
continuum.
Belgian consensus on chronic pancreatitis in adults and children
Epidemiology
 The incidence of CP ranges from 1.6 - 23 cases per
100,000 population per year worldwide.
 Chronic pancreatitis in the United States results in:
- > 122,000 outpatient visits and
- more than 56,000 hospitalizations per year.
Etiology and risk factors of chronic
pancreatitis
 In every CP case, clinicians should attempt to classify the
patient – after a thorough patient anamnesis covering :
- environmental factors, and
- personal & family history, and
- after standardized biochemical, immunological, & genetic
testing,
- detailed imaging studies

into one of the six etiologic groups of the TIGARO
classification
Belgian consensus on chronic pancreatitis in adults and children
Etiologic groups of chronic pancreatitis
according to the TIGAR-O classification system
Belgian consensus on chronic pancreatitis in adults and children
TIGARO classification
Pathophysiology
Ductal theory
(ducts are primary targets)
Acinar theory
(Toxic-metabolic
hypothesis)
Necrosis-fibrosis
theory
Strictures or stones
Etoh & metabolites
Repeated acute pancreatitis
Injure acinar cells
Cellular necrosis/apoptosis
Obstruction
Damage pancreas and
activate pancreatic
stellate cells
Chronic pancreatitis.
Chronic pancreatitis
Healing replaces necrotic
tissue with fibrosis
Chronic pancreatitis
Types according to etiology
Alcoholic CP (ACP)
 Pancreas processes ethanol efficiency but metabolites injure
acinar cells & activate stellate cells.
 Duration : Usually > 10-15 yrs with > 150g/day etoh
 < 10% heavy alcoholic s developed disease
cofactors are:
- genes,
- diet high in fat/protein,
- type of ethanol,
- deficiency of antioxidant or trace element,
- smoking
 Up to 40% of AAP does not progress to clinical CP though
may have histologic evidence.
 Some pts had ACP without having acute episodes previously.
 Stopping etoh ↓ rate of progression to exocrine and endocrine
insufficiency but does not stop it , but does ↓ recurrent AAP.
Idiopathic CP
Account for 10-30% of all CP
Two presentations
1. Early-onset (20-30y/o):
 Predominant feature of
pain;
 Calcification, exocrine &
endocrine insufficiency are
rare at presentation &
develops slowly (~ 25years)
 Complications occur in
20% of pts,
 Surgery for abd pain
ultimately indicated in
60% of pts.
2. Late onset (60-70y/o):
 Presents with less pain but
more commonly exocrine
and endocrine insufficiency
(40% at presentation).
Smoking
 Exposure to tobacco smoke shown to induce pancreatic
damage in animals.
 Common in Alcoholic CP and assoc. with ↑ panc.
calcifications and cessation after clinical onset, ↓ risk of
subsequent calcifications
 Strong independent risk factor for CP
 Associated with high rate of:
- secondary pancreatic cancer and
- overall mortality in pts with CP
Tropical pancreatitis
 Most common form of CP in southwest India, also reported
in Africa, SE Asia, Brazil.
 C/O:
- Abd. pain,
- severe malnutrition,
- exocrine or endocrine insufficiency
- rarely steatorrhea
-high rate of DM ( fibro calculous pancreatic diabetes),
 characterized by:
- large intra-ductal stones,
- markedly dilated main PD and
- gland atrophy.
 Unclear pathophys : ? ?
- genetic mutations, environmental triggers such as protein-calorie malnutrition,
- deficiencies of trace elements and micronutrients + oxidative stress,
- cyanogenic glycosides in cassava (tapioca – main dietary component),
- viral and parasitic infection.
Hereditary(Genetic) Pancreatitis
 Definition :
 Autosomal dominant
 Characterized by recurrent
attacks of severe pancreatitis
 Affect > 2 family members
 80 % penetrance
 Germline(inherited) mutation in
 Typically present by age of
PRSS1-cationic trypsinogen
gene
 Trypsin becomes resistance to
cleavage
 It can activate other digestive
enzymes giving rise to pancreatitis
20 years
 Increased risk of cancer
 Imaging:
- Calcification of pancreas
- Irregular dilated pancreatic
duct
Autoimmune pancreatitis
 AIP is best described as the pancreatic manifestation of a systemic
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fibro-inflammatory conditions ,as a part of IgG4 related systemic
diseases.
May be isolated ,or ass with IBD, PBS or Sjogren syndrome .
AIP mimics pancreatic cancer
AIP is predominantly seen in males over the age of 50 years.
Obstructive jaundice is the most common presenting symptom.
There is a classic presentation, which includes :
- obstructive jaundice,
- sausage shaped pancreatic enlargement with a low density rim,
- serum IgG4 elevation and
- dramatic response to steroids
 Relapses are quiet common and may need a prolonged course of steroids
Asian Diagnostic Criteria for AIP 2008
 Criterion I Imaging
 Both of the following criteria are required:
- Imaging of the pancreatic parenchyma: diffuse/segmental/focal
enlargement of the gland, occasionally with a mass and/or
hypo-attenuation rim
- Imaging of the pancreatic biliary ducts: diffuse/segmental/focal
pancreatic duct narrowing often with stenosis of the bile duct
Criterion II Serology :
- One of the following criteria are required:
- High levels of serum IgG or IgG4
- Detection of autoantibodies
Criterion III -Histopathology of Pancreatic Biopsy Lesion
- Lymphoplasmacytic infiltration with fibrosis (LPSP) &
- abundant IgG4 positive cell infiltration
Obstructive Chronic Pancreatitis
 Refers to distinct entity of generally single dominant
narrowing or stricture of main PD and related CP of
upstream glands.
 Pancreas divisum 4-11% population: Minor papilla
stricture
dilation of dorsal pancreatic duct
bile
obstruction
?acute pancreatitis and ↑ risk of CP

Treatment : Minor papilla sphincterotomy and stenting
 Sphincter of Oddi dysfunction:
- more ass. with acute or recurrent AP.
Miscellaneous Causes
 Recurrent or severe AP of any etiology
 HyperTG : (>1000mg/dl)
repeat clinical and subclinical
acute inflammation
CP
 Surgical necrosectomy or severe necrotizing gallstone
pancreatitis: assoc with exocrine and endocrine insuff and
↓ pancreatic function tests (PFTs)
 Asymptomatic pancreatic fibrosis
 ↑ frequency of CP in ESRD pts on HD ? CKD produce
asymptomatic pancreatic fibrosis
Diagnosis
Clinical Feature
 Abdominal Pain
- Described as boring, deep, penetrating epigastric pain
radiating to back, relieved by sitting or leaning forward;
- knee-chest position on left side, or squatting and clasping
knees to chest ; worsens with food % at night.
 Observation study show :
- ↓ pain over time,
- relief occur at time of development of diffuse calcifications,
- exocrine and endocrine insuff,
- “burn out” pain over time.
Steatorrhea
 Occurs when lipase < 10 % max output ~ feature of
advanced CP.
 Azotorrhea (protein maldigestion) if < 10 % proteases.
 Fat maldigestion occurs earlier, more severe than protein or
carbohydrate maldigestion.
 Characters of diarrhea:
- wt lost,
- bulky foul-smelling stools,
- Oil droplets, usually 3-4 bm/day
Diabetes
 Esp. common post pancreatic resection and tropical
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


(fibro calcific) pancreatitis.
Islet cells relatively resistant to destruction –mechanism of
disease complex
DM in CP is different from type 1 or 2 –
insulin producing beta and glucagon-producing alpha cells
injured ↑ risk of severe hypoglycemia with insulin ttt.
DM is as common as steatorrhea, median time to develop
~6-10 years.
Risk factors for DM :
- early onset pancreatic calcifications
- and resection of pancreatic tail.
 Weight loss (uncommon) due to :
- usually during painful flares or
- if concomitant SIBO or
- pancreatic or extra-pancreatic malignancy,
- severe etoh use
 Fat soluble vitamin deficiency
 Vit D deficiency
osteopenia (50-70% pts) and
osteoporosis (20% pts)
Classics of Chronic pancreatitis
 Pancreatic calcification
 Steatorrhea
 Diabetes mellitus

 Found in less than a third of pts with CP
How should chronic pancreatitis be
classified ?
I.
Pre-clinical stage with absent
or uncharacteristic symptoms
II.
Recurrent acute episodes of
pancreatitis without definite
signs of CP
III.
Further recurrent episodes with
intermittent or constant pain in
between and signs of CP, such
as duct dilatation and pancreatic
calcification on imaging
IV.
Final stage, mostly without acute
flares and absence or decreased
frequency of pain, possibly
associated with evidence of
endocrine and
exocrine insufficiency (burnout)
Diagnosis
 No single test is adequate
 Tests for function
 Tests for structure
 Both are more accurate in advanced disease
 Indicate large reserve functionally, late structural changes
 Big duct vs small duct disease
Tests of function
( hormone stimulation )
 Secretin/ secretin CCK


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
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test
Fecal elastase
Fecal chymotrypsin
Serum trypsinogen
(trypsin)
Fecal fat
Blood glucose
Tests of structure





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Endoscopic US
ERCP
MRI/MRCP
CT
Abdominal US
Plain abdominal film
Abnormal secretin stimulations test when >60 % affected
- Serum trypsinogen < 20 ng/ml,
- fecal elastase < 100 mcg/mg stool - severe exocrine insuf.
You shoul be very alert
!!!
Or you may loose your pateint
Imaging studies
 Belgian consensus on chronic pancreatitis in adults
and children: Statements on diagnosis and
nutritional, medical, and surgical treatment.
Delhaye M et al; Acta Gastro‐Enterologica Belgica 2014.
– U/S 1st‐line imaging CP; MRCP after secretin 2nd step
– Attempt to determine etiology: contributory genetic
etiology esp. CFTR, SPINK, PRSS1; “CTRC only recently
screened”
 Management conservative; ERCP for strictures and
stones
Plain X- ray
CT, MRCP, US
 Calcifications
 Ductal dilatation
 Enlargement of the pancreas
 Fluid collections (eg, pseudocysts)
Indications of ERCP
 Choice when calcifications
are not present and there
is no evidence of
steatorrhea.
 A normal study should notd
rule out the diagnosis of
chronic pancreatitis
 Provide useful information
on the status of the pancreatic
ductal system
 Abnormalities include :
1)luminal narrowing
2) Irregularities in the ductal
system with stenosis,
dilation, saculation,and
ectasia
3)Blockage of the duct by
calcium deposits
Endoscopic ultrasonography

The most predictive endosonographic feature is the presence
of stone

Other suggestive features include:







visible side branches
cysts
lobularity
irregular main pancreatic duct,
hyperechoic foci and strands
dilation of the main pancreatic duct
hyperechoic margins of the main pancreatic duct.
EUS
Complications
 Pseudo cyst formation
 Bile duct or duodenal obstruction
 Pancreatic ascites or pleural effusion
 Splenic vein thrombosis
 Pseudo aneurysms
 Pancreatic cancer
 Acute attacks of pancreatitis( particularly alcoholics
who continue drinking)
DIFFERENTIAL DIAGNOSIS
 Pancreatic cancer (most important)











older age
absence of a history of alcohol use
weight loss
a protracted flare of symptoms
onset of significant constitutional symptoms
pancreatic duct stricture greater than 10 mm in length on ERCP
Markers such as CA 19-9 and CEA
Peptic ulcer disease
Gallstones
Irritable bowel syndrome
Acute pancreatitis
Algorithm for investigation
Abdominal plain film
CT or US
MRCP
ERCP or EUS
Direct PFT
Consider other diagnosis
+
+
+
+
+
+
Chronic pancreatitis
Patient with suspected CP
(Abd. pain , jaundice, elevated serum amylase , lipase& liver enzymes
Contrast enhanced CT
Diagnostic for CP
If contemplating surgery
for stone , stricture or
pseudocyst consider
MRCP or EUS
To identify ductal
anatomy
Normal CT, but high
index of suspicious of
CP
Cystic or mass lesions
Suspicious of
malignancy
Consider EUS with FNAB
And pancreatic function
test
Consider EUS with
FNAB; fluid also can be
analyzed for tumor
markings eg,.CA19-9
‫مكـة المكـــرمة‬
Management Options for CP:
 PAIN : symptom affecting QOL
 Issues of exocrine, endocrine Insufficiency
 Managing Complications: stones, pseudocysts
- Medical
- Endoscopic
- Surgical
A. Pain in chronic pancreatitis
- Pain is the most disabling symptom in CP , which
significantly impacts QOL, and
- Is caused by several pathophysiological mechanisms.
- It should be assessed using the Izbicki score.
- The “pain ladder” approach is recommended for pain
treatment.
- In refractory cases, alternative treatments are
available
Belgian consensus on chronic pancreatitis in adults and children
IZBICKI pain score
Belgian consensus on chronic pancreatitis in adults and children
Pain Management
Traditional “Stepwise” Approach
 Stopping toxins; small meals and supplements




+/‐ Pancreatic enzyme supplements, acid suppression
+/‐ Antioxidants?
(negative: Gastro 2012 ANTICIPATE)
Analgesics: acetaminophen, NSAIDS; narcotics,
centrally acting agents (“neuropathic”), celiac nerve
blocks
Endoscopic therapies: decompression, stones, stents
Surgical options: decompression, resections
Dilemma: When do you become more aggressive?
vs Q. Harm of waiting “too long”?
Pancreatic enzyme supplements
 Not very effective
 Response may be better in young women with small duct
disease.
 MECHANISM:
 Suppression of feedback loops in the duodenum that regulate the
release of cholecystokinin (CCK), the hormone that stimulates digestive
enzyme secretion from the exocrine pancreas
 Six tablets of Viokase® which contains:
 16,000 units of lipase
 30,000 units of protease
 30,000 units of amylase.
 Pancreatic enzyme replacement
 2-3 enteric coated or 8 conventional tablets with meals
 adjuvants with conventional tablets – H2 blockers, PPI,
Na bicarbonate,
 Ca carbonate and Mg OH may even ppt steatorrhea.
 Steatorrhea
- Can be abolished if 10 % of normal lipase amount can be
delivered to the duodenum at the right time
 Limitations




Lipase is inactivated by gastric acid,
Food and enzyme emptying from the stomach is different,
Variable enzymatic activity of the preparation,
High potency prep.
1.Pancreatic enzyme therapy
30,000 iu Lipase/meal
Symptoms continue
2.Low fat diet
(50-75 gm/day)
Symptom
resolution
Symptoms continue
3.H2-receptor antagonist
Symptoms continue
4.Proton Pump Inhibitors
Symptoms continue
Failure: -False diagnosis
- Concomitant mucosal diseaese
Incorrect timing of medications - Loss of potency of enzymes
Analgesics
 If pancreatic enzyme therapy fails to control pain.
 Short course of narcotics coupled with low dose amitriptyline
and a NSAID.
 Simultaneous short-term hospitalization, with the patient kept
NPO to minimize pancreatic stimulation, may also be of
benefit in breaking the pain cycle.
 Chronic narcotic analgesia may be required in patients with
persistent significant pain.
 Long-acting agents such as Fentanyl patches are generally
more effective than short acting medications, which
last only three or four hours.
Surgery
Specialized approaches
 Celiac nerve blocks
 Endoscopic stenting of the pancreatic duct or pancreatic
sphincterotomy
 Extracorporeal shock wave lithotripsy
 Surgery
Indications for surgery
 Biliary or pancreatic stricture
 Duodenal stenosis
 Fistulas(peritoneal or pleural)
 Hemorrhage
 Intractable chronic abdominal pain
 Pseudocysts
 Suscpected pancreatic neoplasm
 Vascular complications
Surgical Interventions:
For Pain, Complications
 • Types:
– Decompression procedures for dilated PD
– Resections of affected portion of pancreas
– Denervation procedures: Ie splanchnicectomy
Total Pancreatectomy‐
Islet AutoTransplantation (TP‐IAT)
 Rationale TP: Removing all offending tissue to eliminate
pancreatitis, inflammation, pain, cancer risk
 Rationale IAT: To preserve islet cells to protect patient
from brittle type 3c diabetes
 Concerns:
– Irreversible; surgical complications
– Pain relief not always experienced
– Diabetes protection variable ; need pancreatic enzymes
– “Exchanging one chronic disease for another”
Specialized centers, criteria
Management algorithm for CP
Endocrine insufficiency
Diet ,insulin
Oral hypoglycemic agents
Pain
Exclude complications like ; cysts
Biliary or Duod. obstruction,cancer
Exocrine insufficiency
Enzyme
supplementation
Trial of medical ttt, analgesics, pancreatic
enzymes, antioxidants
Small duct disease
- Analgesics,
- Pancreatic enzymes,
- Antioxidants
- Pregabalin
- Nerve block
- Surgery
Pain persists
Endoscopic ttt (endotherapy)
- Stricture dilation
- Stent insertion
- Stones removal
- Minor papillotomy
Fail
Large duct disease
Pancreatic head mass
- Multiple strictures
- Stricture at tail of pancrease
-Multiple large duct calculi
- Duodenal obstruction
Surgery
Pain in chronic pancreatitis could be improved with all,
except?
 A)Antibiotics
 b) Narcotics
 c) Celiac block
 e) Surgical drainage
 f) Pancreatectomy
‫جـــــزاكــــم اللــــه خــــــيرا‬
‫علـــى‬
‫حســـن استمــــاعكــــم‬
‫‪69‬‬
‫‪2004‬‬