Chronic Pancreatitis

DR.(PROF.)BALVIR SINGHMD MEDICINE, FICP, FIACM, MAMS,INCHARGE- GASTROENTEROLOGY& ENDOSCOPY UNITS N MEDICAL COLLEGE AGRA

Chronic pancreatitis represents a continuous, prolonged, inflammatory and fibrosing process of

the pancreas with irreversible morphologic changes resulting in permanent endocrine and exocrine

pancreatic dysfunction. -Harrisons 18th Ed.

Acute pancreatitis and chronic pancreatitis are assumed to be different disease processes, and most cases of acute

pancreatitis do not result in chronic disease.

PREVALANCE

10-15/1,00,000 in western countries.

114-200/1,00,000 in southern India.

Typical age 35-55yrs

Chronic pancreatitis

Pathophysiology

Etiology

Clinical features

Diagnosis

Management

Complications

PATHOPHYSIOLOGY

Incompletely understood

Why 10% heavy alcoholics develop chronic pancreatitis and the rest not, or limited to asymptomatic pancreatic fibrosis

Alcohol is the most studied

Ductal obstruction hypothesis

Chronic alcohol

use

acinar and

ductal cell

protein rich

pancreatic juice, low in

volume and

HCO3

formation of

protein precipita

tes – plug

calcification of ppt – ductal stone

formation

ductule obstruct

ion

parenchymal

damage

Pancreatic ductal stone are seen in alcoholic, tropical, hereditary, idiopathic

Sleisenger and Fordtran’s - 10h edition.

Toxic metabolic hypothesis

(alcohol) Direct injurious effect on acinar and ductal cells

Increased membrane lipid peroxidation (oxidative stress), free radical production

Increase acinar cell sensitivity to pathogenic stimuli

Stimulate CholeCystoKinin(CCK) production (duodenal I cells) – activation of proinflammatory transcription factor

Necrosis fibrosis hypothesis

Repeated episodes of acute pancreatitis with cellular necrosis or apoptosis, healing replaces necrotic tissue with fibrosis

Evidence from natural history studies - more severe and frequent attacks

•Cystic fibrosis is assosiated with abnormalities of HCO3 secretion, ductal dilatation, ppt formation, pancreatic atrophy•Seen in 50% of idiopathic CP, not common in alcoholic CP

CFTR – cystic fibrosis

trans-membrane conductance

regulator

• Seen in pediatric Idiopathic CP, hereditary Pancreatitis, Tropical Pancreatitis; but not in chronic alcoholic pancreatitis

SPINK1 - serine protease inhibitor

Kazal type 1

Genetic forms

• Once trypsinogen is activated to trypsin, becomes resistant to inactivation and activate other proenzymes leading to episodes of acute pancreatitis– like necrosis fibrosis theory

PRSS1 – cationic trypsinogen gene

Etiologic factors associated With CP: TIGAR-O

TROPICAL PANCREATITISAfrica, India(AP,TN,KERLA), Brazil

A disease of early childhood and youth

> 90% before age of 40yrs

Prevalence in endemic areas: 1 in 500-800

Abdominal pain, malnutrition, exocrine and endocrine insufficiency Pancreatic caliculi – 90%

50% SPINK1 gene mutation.

AutoImmune Pancreatitis

5% of CP, more in males, middle age

12 – 50% ass. With other autoimmune diseases

abdominal pain, weight loss, jaundice

Imaging studies show focal or diffuse (sausage shaped) enlargement Diagnosis – clinical, imaging, IgG4, autoantibodiesTreatment – glucocorticoids 1-2m and tappering in 3-4m

Idiopathic Pancreatitis

Early onset • 20yr mean age, male=female• 96% pain• Calcification, exocrine or endocine

insufficiency develop slowly over time – 25, 26 -27.5 yrs

• CFTR, SPINK1 genesLate onset• Pain is less frequent 54%-75%• Age of onset 56yrs, m=f• 90% calcification is seen

• Chronic pancreatitis is a relapsing condition that presents with abdominal pain, occurring in 95% of cases.

• Pain;most common clinical feature, can be episodic, lasting hours to days, or it can persist for months or even years. The pain is characteristically steady in the epigastrium, and it frequently radiates to the back.

• Mechanism; increased pressure &ischeamia• Alteration in nociceptive nerves• Increased CCK level• Weight loss, • Steatorrhea. When <10% exocrine function remains• Azotorrhoea fallowed by carbohydrate maldigestion

Clincal features

Diabetes mellitus

1% of DM from CP some times called Type3 diabetes

• abnormal duct in 40-50% , • abnormal pancreatic function in 40-50%

In DM - pancreas is smaller,

Insulin is a trophic factor for exocrine function of the pancreas

Insulin deficiency + microangiopathy of DM lead to pancreatic damage

DM and CP cause effect relation is not clear

Diagnosis

▪ No single test is adequate ▪ Tests for function▪ Tests for structure ▪ Both are more accurate in

advanced disease .

Tests of function – hormone stimulation

• Direct Tests• Secretin/ secretin CCK stimulation test• Procedure- administer 0.2 mcg/kg recombinant

secretin and sample collected either by dreiling tube or endoscope over 60 mnts at 15 mnt aliquots and samples were analysed for HCO3 concentration

• Abnormal test;HCO3 conc. <80meq/ltr• Sentivity 74-90% ,specificity 80-90% • Measure HCO3/enzyme output by putting

orodeuodenal tube

• Fecal elastase<200mcg/gm of stool• Fecal chymotrypsin• Serum trypsinogen (trypsin)-<20ng/ml• Fecal fat-pt must take 100gm/day fat

3days prior to test 72 hrs stool collected-positive result >7gm of fat and >6 fat globule per HPF in microscope

• Blood glucose

Indirect Tests

Routine labarotory tests

Serum amylase and lipase

• May be elevated in acute exacerbations• Also found increased in pseudocyst,

ductal stricture, internal pancreatic fistula,pancreatic carcinoma,cholecystitis,ectopic pregnancy

Tests of structure• Plain film of the abdomen• CT• Ultrasonography • MRI, • particularly MRCP • ERCP

• Pancreatic calcifications are shown in 25-59% of patients. • This feature is pathognomonic for chronic pancreatitis. • Calcification is punctate or coarse, and it may have a focal, segmental, or

diffuse distribution.

chronic pancreatitis with marked calcification of the pancreatic parenchyma.

Plain films

The anatomic proximity of the pancreatic head and stomach antrum is constant, and enlargement of the pancreatic head usually causes effacement of the antrum. This finding has been termed the pad sign.

Upper gastrointestinal tract barium study shows a reverse 3 in the duodenum due to chronic pancreatitis.Pancreatic carcinoma can have a similar appearance

Upper GI tract barium series

Currently, CT is regarded as the imaging modality of choice for the

initial evaluation of suggested chronic pancreatitis.

The diagnostic features of:• pancreatic enlargement, • pancreatic calcifications, • pancreatic ductal dilatation,• thickening of the peripancreatic

fascia, and • bile duct involvement are depicted well on CT scans.

CT Findings

The sensitivity of plain film for detection of pancreatic calcifications is about 80 %, which is higher than that of sonography but lower than that of CT.

CT Findings

• Ultrasonography is the first modality to be used in patients presenting with upper abdominal pain, although the direct diagnosis of chronic pancreatitis is not always possible.

• In early disease, the pancreas may be enlarged and hypoechoic, with ductal dilatation. Later, the pancreas becomes heterogeneous, with areas of increased echogenicity and focal or diffuse enlargement.

Chronic pancreatitis in phase of exacerbation - an uneven outline of the

gland and heterogeneous structureof pancreatic tissue.

ULTRASOUND

• In late stages of the disease, the pancreas becomes atrophic and fibrotic, and it shrinks. These changes result in a small, echogenic pancreas with a heterogeneous echotexture.

• Pseudocysts may occur, and focal hypoechoic inflammatory masses may mimic pancreatic neoplasia.

• Calculi and calcification in the gland result in densely echogenic foci, which may show shadow

ULTRASOUND

ERCP is the most sensitive and specific technique in the investigation of chronic pancreatitis, although it is invasive and may cause an acute episode of pancreatitis and ascending cholangitis.

Endoscopic retrograde cholangiopancreatography (ERCP)

ERCP of normal pancreatic and biliary ducts.

ERCP

Endoscopic retrograde cholangiopancreatography (ERCP)

Mild pancreatitis may present with minimal dilation of the main pancreatic duct and some clubbing of the side branches of the duct

ERCP

Chronic Pancreatitis Endoscopic retrograde cholangiopancreatography (ERCP)

The patient with moderately-staged chronic pancreatitis shows moderate dilation of the main pancreatic duct (1.5 times the normal size) This is accompanied by moderate clubbing of the side branches of the main pancreatic duct

ERCP

Chronic Pancreatitis Endoscopic retrograde cholangiopancreatography (ERCP)

A characteristic "chain of lakes" appearance of the main pancreatic duct can be noted on ERCP in patients with severe chronic pancreatitis. The main pancreatic duct is enlarged (greater than 1.5 times) with increased tortuosity.There is severe clubbing and dilation of the side branches. Stone formation and occlusion of the pancreatic duct may occur in this stage of the disease

ERCP

Chronic Pancreatitis MRI, particularly MRCP, is a noninvasive technique. The combination of pancreatic parenchyma imaging sequences with MR angiography and secretin-enhanced MRCP offers the possibility of a comprehensive examination within a single diagnostic modality for evaluation of the full range of pancreatic diseases. (A) MRCP demonstrates a "double duct" stricture with proximal dilatation

of the common bile duct and pancreatic duct (arrow). A cystic lesion is seen between the common bile duct and the duodenal wall. (B) Fat-suppressed TSE T1-weighted image. Unenhanced (C) and delayed gadolinium-enhanced (D) T1-weighted images, demonstrate diffuse enhancement of the sheetlike mass, which corresponded to fibrotic tissue.

Groove pancreatitis

MRI

Classics of Chronic pancreatitis

Pancreatic calcification

• abnormal secretin stimulations test when >60 % affected• Serum trypsinogen < 20ng/ml, • Fecal elastase < 100mcg/mg stool - severe exocrine insuf.

Steatorrhea

Diabetes mellitus

Found in less than a third of pts with CP

34

Treatment

▪ Aim-Pain control and management of maldigestion

▪ Pain ▪ Analgesics-narcotics, SSRI,TCA,Gabapentine

▪ Avoid alcohol And tobacco▪ Low fat meals▪ Steatorrheoa▪ Pancreatic enzymes- REDUCES CCK reduces

secretory function and reduces pain▪ Non enteric coated Pancrelipase

▪ Creon,Panlipase▪ Ultresa.

▪ Octreotide-dual action ▪ Reduces pain by decreasing CCK▪ Nociceptive pain modification

Endoscopic Treatment

Endoscopic treatment

• Sphinctorotomy,• dilatation of strictures• caliculi removal• duct stenting

Complications–acute pancreatitis,Abscessductal damagedeath

Surgical Treatment

▪ Interactable pain control▪ Ductal drainage procedure

▪ Resection by WHIPPLE Procedure (local-95%) –causes pancreatic insufficiency

▪ Roux –en-Y▪ Splanchinectomy▪ celiac ganglionectomy▪ nerve block

Treatment of maldigestion

▪ Pancreatic enzyme replacement▪ 2-3 enteric coated with meals▪ adjuvants with conventional tablets – H2 blockers,

PPI, Na bicarbonate, ▪ Steatorrhea can be abolished if 10 % of

normal lipase amount can be delivered to the duodenum at the right time.

Approach

Complications

Chronic abdominal pain bile duct obstructionNarcotic addiction splenic vein thrombosisDM fistulasGastroperesis retinopathy

Maldigestion GI bleed

▪ joundice▪ Pseudocyst Cancer Pseudoaneurysm

Chronic Pancreatitis Occurs in 25%, mostly in alcoholics• Manifest as pain,mass ,nousea and vomiting• Diag. by usg,ct ,MRI,EUS• compressoion to vessels doudenum/stomach

infection,heamorrhage and fistula• Therapy for symptomatic ,complicated cyst can

be by-• surgical ,• percutaneous or• endoscopic drainage

(cystogastrotomy/cystojejunostomy)

pseudocyst

• Diabetes :• can develop in 70-90% of patients with chronic calcific

pancreatitis• Fistula formation-• external-due to surgical or percutaneous drainage• Internal- due to rupture of pseudocyst leading to

pacreatic ascites or pleural effusion • Diagnosed by high level of amylase>400U/ml• Pseudoaneurysms of large arteries close to the

pancreas• Stenosis of the common bile duct• Splenic and/or portal venous obstruction• Malignancy – incidence 4% CA 19-9 negative

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