Thuy Anh Le, MD May 31, 2011

Background CP is progressive inflammatory disorder where

pancreatic secretory parenchyma is destroy and replaced by fibrous tissue leading to malnutrition and DM.

Acute, recurrent acute, and CP thought as a disease continuum. Recurrent acute pancreatitis (AP) can develop into CP.

26,000 first listed diagnosis for admissions/year Prevalence has geographic variation Japan

35.5case/100K vs 26case/100K France most studies on alcohol CP.

Pathophysiology Ductal theory (ducts are primary targets):

strictures or stones obstruction CP. Acinar theory (Toxic-metabolic hypothesis):

etoh and metabolites injure acinar cells damage pancreas and activate pancreatic stellate cells

Necrosis-fibrosis theory: repeated acute pancreatitis cellular necrosis/apoptosis healing replaces necrotic tissue with fibrosis chronic pancreatitis. Supported by animal models and human studies

Pathophysiology (cont) Electrophilic stress theory: insufficient

protection by glutathione against electrophilic attack.

Cotoxins: tobacco Genetic or epigenetic background:

unexplained racial differences in rates of alcoholic chronic pancreatitis (ACP)

Mutations may produce or predispose to CP (CFTR, PRSS1, SPINK1).

Differences in microenvironment of the pancreas

Pathophysiology (cont) Background of gene mutations +/- environmental insult (etoh)

Activation of digestive enzymes w/in acinar cell inflammation progress or resolve

Continued cell metabolic and oxidative stresses or other trigger continue or repeated acinar cell injury with necrosis

Switch to anti-inflammatory response: resident macrophages produce cytokines and activated stellate cells lay down

extracellular matrix and fibrosis

Fibrosis start vicious circle of acinar cell ischemia and drive inflammatory-anti-inflammatory cycle.

Etiology

Excluding CF, 90-95% pts has alcoholic or idiopathic disease, rarely infectious, and drug induced causes are anecdotal.

Alcohol: cause of >70% of CP Idiopathic Toxic causes: i.e. tobacco Autoimmune: 2-4% cases - will not discuss

during this lecture Genetic

Alcoholic CP (ACP) Pancreas processes ethanol efficiency but metabolites injure

acinar cells & activate stellate cells. Usually >10-15 yrs with >150g/day etoh

Idiopathic Accounts for 10-30% of all CP Early-onset (20-30y/o): M=F,

Predominant feature of pain; calcification, exocrine & endocrine insufficiency rare at presentation & develops slowly (~mean 25years)

Complications in 20% pts, surgery for abd pain ultimately in 60% pts.

Late onset (60-70y/o): M=F Presents with less pain but more commonly exocrine

and endocrine insufficiency (40% at presentation) with median time to development of 16 and 11yrs respectively.

Smoking Exposure to tobacco smoke shown to

induce pancreatic damage in animals. Common in ACP 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 forms of CP in southwest India, also

reported in Africa, SE Asia, Brazil. Mean age 24y/o (>90% pts

Genetic PRSS1-cationic trypsinogen - (only mutation

sufficient to cause CP, others are co-factors) Causes hereditary pancreatitis by gain of function

trypsinogen activated to a trypsin form that is resistant to inactivation

SPINK1-trypsin inhibitor-associated with idiopathic CP

CFTR Abnormal bicarb secretion dilated pancreatic ducts,

intraductal precipitates, and pancreatic atrophy, association with idiopathic CP

>1200 known CFTR mutations

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 (2/2 stricture) dilation of dorsal pancreatic duct bile obstruction ?acute pancreatitis and risk of CP Tx w/ minor papilla sphincterotomy and stenting

Sphincter of Oddi dysfunction: more assoc with acute or recurrent AP. Abnormal sphincter pressures may be 2/2 CP than

cause. Response to sphincter ablation is poor.

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 DM: pancreas smaller (esp. DMI), PD abnormal in 40-50%

diabetic pts on ERCP, PFTs (by fecal elastase measurements or formal PFTs) is abnormal in 40-50% pts.

Wide variety of disease states and normal wear and tear (i.e. aging, etoh use) can produce histologic damage but not clinically significant.

Clinical Feature Abdominal Pain Described as boring, deep, penetrating epigastric pain

radiating to back, assoc n/v, relieved sitting or leaning forward; knee-chest position on 1 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.

Proposed causes Ischemia driven by pressure in ducts and tissues: surgical

drainage of PD pressure and assoc pain relief, not reproducible in ERCP-measured PD and pressure after endoscopic stenting not correlated with pain relief

Alterations in peripheral and central nociceptive nerves Complications of CP (duodenal or bile duct obstruction, pseudocyst

and 2/2 pancreatic CA), hyperstimulation of pancreas by CCK pressure w/in gland

Clinical Feature - Steatorrhea Occurs when lipase

Clinical Feature - Diabetes Esp. common post panc resection and tropical

(fibrocalcific) pancreatitis. Islet cells relatively resistant to destruction

mechanism of dz complex DM 2/2 CP different from type 1 or 2 insulin-

producing beta and glucagon-producing alpha cells injured risk of severe hypoglycemia with insulin tx.

DM is as common as steatorrhea, median time to develop ~6-10 years.

Risk factors are early onset panc calcifications and resection of pancreatic tail.

Diagnosis General classification of dz into: Big-duct dz: abnormal pancreatic duct;

assoc with functional abnormalities as DM or steatorrhea

Small-duct dz (aka minimal-change CP): absence of abnormal PD, less assoc with exocrine or endocrine insufficiency.

Gold standard of pancreatic histology usually not pursued b/c histologic changes not uniform, bx risky.

Pancreatic Function Tests (PFTs) Direct tests Measuring output of bicarb or enzymes from pancreas Study 108 pts combined secretin-CCK

Linear correlation of stimulated bicarb output with histologic severity normal (>80meq/L) vs. 70, 63 and 50 in mild, mod, severe CP with sens 67% and spec 81%

Overall sens 74-97% and spec 80-90% Indentifying pts with CP and functional abnormalities

but not yet have ERCP structural abnormalities Limitations: (1) not standardized (2) Limited to

referral centers (3) pts intolerance of oroduodenal tube for hour or more fore test (4) accurate measurements of [bicarb] and enzymes difficult false + in Billroth II, DM, celiac, cirrhosis, and recent acute pancreatitis

Direct PFTs

Useful in pts with presumed CP but no structural abnormalities, does not want ERCP

Variations of test: Use of sedation ERCP placement catheter into PD to collection

secretions x 15 minutes Sedation-EGD placement of oroduodenal tube

collection over 60min with timed aspirates Measure lipase output rather than bicarb

Pancreatic Function Tests (PFTs) Indirect tests Measuring panc enzymes in blood or stool Serum trypsinogen

Low level (

Imaging studies: X-rays: Diffuse calcifications very spec for CP vs.

focal calc in cystic and islet tumors of pancreas Abd u/s: findings of dilated PD, showing PD stone,

gland atrophy or enlargement, irregular gland margins, pseudocysts, parenchymal echotexture sen 50-80%, spec 80-90% Limited by poor view of pancreas 2/2 overlying gas or body

habitus, difficult to distinguish normal or age-related variability. Normal or severe findings is definitive but mild changes less specific.

CT: sen 75-90%, spec >85%. Most accurate in advanced CP after structural changes developed.

Radiographic Findings:

Grade US or CT findings

Normal No abnormal findings on a good-quality study visualizing the entire gland.

Equivocal One of the following: -Mild dilatation of the pancreatic duct (2-4mm) in the body of the gland -Gland enlargement 2 fold normal

Mild-Moderate One of the preceding findings plus at least one of the following: -Pancreatic duct dilation (>4mm) -Pancreatic duct irregularity -Cavities 10mm -Intraductal filling defects -Calculi/pancreatic calcifications -Ductal obstruction (stricture) -Severe duct dilatation or irregularity -Contiguous organ invasion

Grading of Chronic Pancreatitis by Ultrasonagraphy (US), Computued Tomography (CT)

From Sleisenger and Fordtrans

Imaging studies - cont MRI coupled with MRCP:

MRCP agree with ERCP results in 90% cases more discrepancy where PD is small (tail or side branches) or with subtle ductal changes.

Improved visualization with secretin injection ERCP:

Spec 80-100% and sens 70-90% and is de facto gold standard. Cambridge grading based on abnormalities seen in main PD and

side branches. Requires adequate filling to 2nd generation of side branches and w/o

motion artifacts Limitations: (1) Effect of aging on PD (focal of diffuse dilatation of

main PD and side branches, cystic cavities, and ductal calculi (2) temporary changes after acute panc months to resolve (3) panc adenoma changes resemble CP (4) PD stents produce new abnormalities (5) interobserver and intraobserver variability

Cambridge Grading of Chronic Pancreatitis on ERCP

Grade Main Pancreatic Duct Side Branches

Normal Normal Normal

Equivocal Normal 10mm) -Obstruction -Filling defects -Severe dilatation or irregularity

3 Abnormal

From Sleisenger and Fordtrans

Top: Mild pancreatitis with minimal dilation of main PD and some clubbing of side branches of duct

Bottom: Moderately-staged CP with moderate dilation of main PD (1.5x normal size) and moderate clubbing of side branches.

Severe CP: chain of lakes appearance alternating strictures and dilatation enlarged main PD with increased tortuosity and severe clubbing and dilation of side branches.

EUS: Features graded as present/absent total of 3 is positive. EUS and ERCP agree 80% pts highly accurate in advanced CP Rosemont criteria

Score >5 is high specific, 0-2 r/o CP, and in between considered indeterminate and be interpreted with clinical features.

Diagnosis of Chronic Pancreatitis on Endoscopic Ultrasonography

Parenchymal abnormalities Hyperechoic foci Hyperechoic strands Lobularity of contour Cysts

Ductal abnormalities Main duct dilatation Main duct irregularity Hyperechoic ductal walls Visible side branches Calcifications

Two types of EUS scopes: radial scanning (right) and linear array (left). The radial type scans in a plane perpendicular to the axis of the scope to produce 360 images similar to a CT "slice(bottom right).

The linear array type scans (bottom left) in a plane parallel to the axis of the scope. It has the advantage of allowing visualization of the needle while performing a procedure

Algorithm for diagnosis of CP

TREATMENT

Medical therapy Analgesics

Risk of addiction 10-30%. Broadly follow WHO guidelines for cancer pain.

Tramadol with dual-action analgesic (mu-opioid agonistic and monoaminergic properties) high doses equivalent to oral morphine in CP

Adjuncts: TCAs, SSRIs, and combined serotonin and norepinephrine reuptake inhibitors (duloxetine)

Cessation of alcohol and tobacco Complete abstinence etoh does not prevent progression. Cont etoh use + smoking mortality Most studies show pain or painful relapses in pts who stop

etoh pain cont 26% abstinent pts vs. 53% continued drinkers

Medical therapy (cont) Antioxidants

Pt with CP have oxidant stress (activates pancreatic stellate cells) and antioxidant capacity

Small RCTs showing mixture of antioxidants (selenium, beta-carotene, vit C, vit E and methionine) reduces pain, may curb dz progression

Monitor blood level of plasma and erythrocyte glutathione levels to see increase and check concentrations of micronutrients are not excessive.

Tx for 10 weeks is recommended b/f invasive procedure Octreotide:

pancreatic secretion and CCK levels. Has some direct anti-nociceptive effect separate from any

effect on enzyme secretion. However, largest trial has placebo response of 35-40%

Medical therapy (cont) Pancreatic enzyme therapy

Delivering proteases to duodenum or proximal jejunum denatures CCK-releasing factor CCK secretion pancreatic secretions avoid raising PD or tissue pressure or spilling digestive enzymes into interstitium if secretion occur against PD obstruction pain

Pancreatic secretion of volume and bicarbonate controlled by humoral and neural control so affect of feedback control system (controls enzyme secretion)may be limited.

RCTs 2 studies show non-enteric coated tablet form beneficial, 4 studies show enteric-coated microsphere no benefit. Feedback-sensitive small bowel is most proximal enteric-

coated pills may not release the majority of their proteases until reaching distal small bowel so non-enteric coated may work with concomitant PPI

Best response with less advanced dz, women, and pts with idiopathic CP

Endoscopic Therapy Pancreatic duct sphincterotomy

Therapy for cicatricial stenosis of sphincter causing obstructive CP rare form of CP.

For large stent placement or PD stone extraction. Needle-knife sphincterotome over small-caliber PD stent technique is

safer than pull-type sphincterotome in pts high risk for post-ERCP panc

For pancreas division causing dorsal PD dilation minor papilla sphincterotomy over stent.

Stent placement: to dilate and bypass stricture Large study 1000 pts 57% pt with single dominant stricture had

improve pain at 4.9years, 19% sig pain improvement but required ongoing endoscopic therapy

Sxs recur in 1/3 to 1/2 pts after initial clinical response Mechanism for improved pain unclear intraductal pressures not

clearly associated with pain symptoms. Complications: occur in ~20% pts, mortality 0.6% - (1) clogging of

stents (2) stent migration (3) ductal perforation

Endoscopic Therapy (cont) Pancreatic duct stone removal

Using extracorporeal shock-wave lithotripsy (ESWL) or intraductal instruments

No close correlation b/t presence of stones and pain.

Duct clearance ~60%, pain improvement or relief is 75-90%

RCT of ESWL vs. ESWL + endoscopic removal of stones: pain relapse at 2 years is 38% vs. 45%; tx cost 3x higher in ESWL + endoscopy. Study suggest that ESWL reduce size of stone to not obstructing and could be other effect on pain separate from ability to fragment stones.

Combined Endoscopic Therapy

Randomized 72 pts to endoscopic tx (sphincterotomy, stent therapy, or stone removal) vs. surgery (PD drainage or pancreatic resection) 1 year rates of pain relief similar; 5 years partial pain

relief or absence of pain was 61% vs. 86% - surgical group gained more wt. Limitations of study: endoscopic therapy was less aggressive than optimal and surgery more aggressive (80% had resection)

Randomized to aggressive endoscopic tx (ESWL as needed) vs. surgery (pancreaticojejunostomy or modified Puestow) Trial stopped early after 39 pts recruited d/t better

outcome from surgery Complete or partial pain relief was 32% vs. 75% surgery

Surgical Therapy Ductal drainage procedures Lateral pancreaticojejunostomy or modified Puestow:

PD opened longitudinally and anastomosed to defunctionalized limb of SB connected with Roux-en-Y anastomosis. Strictures incised and stones removed Require dilation of PD to >6-7mm easy ID and

anastomosis. Versus normal duct Puestow procedure Immediate pain relief 80%, long term 50% - unclear

why the decline in pain relief. Trade off b/t simplicity and low risk procedure for

gradual decrease results over time. Exocrine and endocrine unaffected by surgery

deteriorate as in unoperated pts.

Puestow Procedure

Surgical Therapy (cont) Pancreas resection + drainage of PD Whipple resection or Duodenum-preserving Whipple: pain relief

65-95% For pts with dz limited to pancreatic head Mortality at high volume 3%, early post-op complication (disruption of

moral motility and PD leaks) occur 50% cases. Duodenum-preserving pancreatic head resection (DPPHR or

Beger) vs. Frey (less pancreatic head is cored out leaving bile duct and peripancreatic vessels undisturbed) vs. Berne procedure Short term f/u these procedures same efficacy for pain relief more

DM in Whipples. DPPHR + Puestow: 5.7 years f/u 8.7% pts continued to have pain vs.

93% pre-op Beger vs. Frey similar post-op complications, efficacy, long term QoL. Post-op comp more common than modified Puestow but both short- and

long-term pain relief is better.

Whipple Procedure

Surgical Therapy (cont) More pancreatic resection: Resection of body and tail is for dz limited to this

area occurring usually after trauma to PD causing upstream obstruction.

Total or near-total pancreatectomy are rare coupled with islet cell autotransplantation pain relief 80-90% pts, insulin independence 40%

Complications for all surgery for CP: Pancreatic fistula, wound infection, delayed gastric

emptying, intra-abdominal abscess, pancreatitis, cholangitis, and bile leak. Pre- and post-op octreotide may reduce these risks esp. fistula.

Steatorrhea dev in 30-40% pt s/p drainage and 2/3 s/p panc resection. Enzyme supplements for all pts post surg

Distal Pancreatectomy

Nerve Blocks and Neurolysis Celiac plexus block (combo steroids +

long acting anesthetic like Bupivacaine) and celiac plexus neurolysis (injection absolute alcohol) by CT or EUS-guided: rarely use due to short duration of action

Thoracoscopic section of the greater splanchnic nerves to block central perception of nociceptive inputs pain relief 50-75% at 1 year, and 25-50% longer f/u.

Top left: percutaneous celiax plexus nerve block Top right: surgical approach Bottom left: Transgastric approach

Maldigestion and Steatorrhea ~30,000IU (90K USP) of lipase delivered to intestine with

each meal to eliminate steatorrhea - Enzyme supplements content varies usually in USP units.

Most enteric-coated form use microsphere too big to empty from stomach in synchrony with food and may not release contents until reach distal jejunum or ileum too distal to help.

Non-enteric coated give concomitant H2 or PPI. Gauge response by improvement in stool consistency, loss of

visible fat in stool and gain wt. Also check fat soluble deficiencies.

Failure: Inadequate dose or noncompliance change to more potent form. Need to spread out over course of meal and with smaller meals. Look for SIBO or celiac dz Replace dietary fat with medium-chain TG which doe not require

lipolysis or lipase for absorption.

Diabetes

An independent predictor of mortality Some pts may respond to oral

hypoglycemics but most require insulin Usually have lower insulin requirements that

DM type 1. Over vigorous attempts at tight blood

sugar control associated with tx-induced hypoglycemia is indicated in subgroup of hyperlipidemic pancreatitis.

Complications

Pseudocyst Occurs 25% pts with CP most common etoh CP. S/S pain, palpable mass, n/v (compression of

stomach or duodenum) jaundice (comp of bile duct) and bleeding.

Persistent elevated amylase/lipase is clue for pseudocyst.

CT/MRI used to gauge maturity of collection, and relation to other organs, MRI give info on contents (fluid vs. mix of fluid and solid)

70% communicate with PD, ERCP assoc 15% chance of infection of uninfected pseudocyst so do only after antibiotic given and therapy planned

Pseudocyst (cont) Natural hx not well defined, those assoc

with CP resolve far less than with AP and generally mature at time of diagnosis.

Complications occur in 20-40% includes compression of peripancreatic vessels, duodenum, stomach, or duodenum; infection; hemorrhage; fistula formation.

Mature

Pseudocyst (cont) Percutaneous tube drainage in CP pseudocyst discouraged

b/c frequent association with ductal obstruction downstream from fluid collection risk of fistula formation.

Endoscopic tx if collection accessible through papilla or wall of stomach or duodenum. Success rate 70-90%, complications 10% inc bleeding, infection, perforation. EUS-guided puncture help avoid nearby vessels. ERCP with stent placement of PD stricture or large duct disruption risk of pseudocyst recurrence.

Surgery tx: cyst decompression into loop of small bowel or stomach often w/ modified Puestow. Success 90%, mortality

GI Bleed

Pseudocyst: bleeding from small vessels in wall expansion of pseudocyst spontaneous decompression into GI lumen or into PD (hemosuccus pancreaticus)

Variceal bleeding from splenic vein thrombus Causes segmental of L-sided portal HTN

cardia/fundic varices sometimes EV as well. Risk of GV bleeding ~4% Splenectomy is curative for bleeding.

GI bleed (cont)

Pseudoaneurysm: form d/t enzymatic and pressure digestion of muscular wall of artery by pseudocyst. Seen in 21% pts with CP undergoing

angiogram but complicates 5-10% of all cases CP

May bleed into pseudocyst or adjacent viscus, peritoneum or PD.

Mortality at least 40%.

Bile duct obstruction Distal bile duct is w/in head of pancreas, inflammation

and fibrosis or pseudocyst CBD obstruction occurring 10% pts.

ERCP shows long tapered stenosis of distal bile duct In alcoholic pts liver bx may be needed to distinguish

biliary stenosis from intrinsic liver dz Increasing jaundice, biliary pain w/o other causes (i.e.

intrinsic liver dz) is indication for therapy. Definitive therapy: choledochojejunostomy or

choledochododenostomy. Endoscopic stent placement for long term management

requires multiple stent exchanges, & stent migration and obstruction are common.

Use of multiple parallel stents is better than single stent, and high rate of stent occlusion with uncoated stents.

Also must r/o malignancy with dev of new bile duct stenosis

Duodenal Obstruction 5% pts with CP have duodenal stenosis

associated with chronic inflam panc head Dx best with CT w/ oral contrast or UGIS b/c

extent of stenosis underestimated by EGD Trial of medical therapy to reduce inflammation surgery if conservative tx fails ~ bypass w/ gastrojejunostomy +/- drainage of bile duct and/or panc duct.

Resection of panc head can be considered at centers with high expertise for large inflamm mass or whom malignancy is a concern

Pancreatic Fistula External:

Usually occurs 2/2 surgical or percutaneous tx heals with complete bowel rest and hyperalimentation +/- octreotide 100ug SQ q8h can hasten closure can take weeks

Complications of abscess, bleeding. 75% pancreaticocutaneous fistula treated

endoscopically coupled with drainage of intra-abdominal collections.

Surgery for failed endoscopic therapy pancreatic resection (if fistula in tail) or fistulojejunostomy (fistula tract is capped with defunctionalized limb of jejunum.

Pancreatic Fistula Internal Occurs 2/2 rupture of pseudocyst fluid track to

peritoneal cavity (pancreatic ascites) or pleural space (pancreatic pleural effusion)

Pts may deny pain but c/o abd distention or sob, and some has no clear cut hx recent pancreatitis

Dx with high levels amylase in fluid, >4000U/L Conservative tx: bowel rest, parenteral

hyperalimentation, paracentesis or thoracentesis, octreotide, or PD stent highly effective (less effective for leak in tail of upstream from obstructed PD) surgery if tx fails

Malignancy Lifetime risk of panc cancer in CP is 4% - risk

highest in hereditary pancreatitis and smokers No reliable way to differentiate CP from CP c/b

adenoCA EUS is superior to CT or detecting coexisting

malignancy and allow bx, in some laparotomy is needed to make diagnosis

CA19-9 in 70-80% in panc adenoCA Incidence of extrapancreatic CA in pts with CP is

4-12% - most commonly upper GI cancers and lungs - ?related to concomitant tobacco use.

Dysmotility

Gastroparesis and antroduodenal dysmotility seen in CP - ?2/2 perigastric inflammation, hormonal changes assoc with CP or SE of narcotics.

Prognosis

Variable, depends on ongoing alcoholism or tobacco use

10 year survival 70%, and 20 year survival 45%

Cause of death is from other medical conditions associated with smoking, cont etoh abuse, pancreatic carcinoma, and post-op complications

References:

Sleisenger and Fordtrans 9th edition Braganza J. et al. Chronic pancreatitis.

The Lancet 2011; 377: 1181-97. DiMagno M. and DiMagno E. Chronic

pancreatitis. Current opinion in gastroenterology 2010. 26: 490-498.

Pictures Jonhs Hopkins GI website http://www.hopkins-gi.org

Q7:

Mutations in most of the following genes may cause acute and/or chronic pancreatitis.

Which one is the exception? A. Amylase B. Cationic trypsinogen C. SPINK1 D. Chymotrypsinogen C

A7: ANSWER: A The most common class of gene mutations that has

been associated with pancreatitis is trypsinogen . It is thought that trypsinogen mutations promote the development of pancreatitis by favoring generation of trypsin within the acinar cell. These mutations appear to enhance trypsinogen activation, reduce the levels of trypsin inhibitors, or decrease its degradation. \'Vhile mutations in the trypsin inhibitol; SPINKl and chymotrypsinogen C, increase the risk of developing pancreatitis, mutations in amylase are not associated with this disease. !2

Q14 A 30-year-old woman is evaluated for chronic relapsing abdominal pain that

is worse after meals. She underwent a laparoscopic cholecystectomy 3 years previously for chronic cholecystitis. She does not drink any alcohol and has only experienced weight loss of a few pounds over the last year. Her CBC and liver enzymes were normal. Her amylase level has been slightly elevated on occasions (

A14 Answer: D Patients with pancreas divisum who have chronic pancreatitis and pain

rarely respond to minor papilla sphincterotomy. Endoscopic therapy in the setting of pancreas divisum is most beneficial in patients with recurrent acute pancreatitis. Celiac plexus block is Ilighlyeffective for short-term pain relief associated with pancreatic ca rcinoma; however, it is rarely effective in patients with chronic pancreatitis. A lateral pancreaticojejunostomy is indicated for duct decompress ion in the setting of a dil ated main pancreatic duct. Pancreatic enzyme supplements are effective fo r pain relief by enhancing feedback inhibition of pancreatic secretion and appear to be most beneficial in patients with "small duct" chronic pancreatitis without steatorrhea. These patients have relatively normal pancrcatograms without duct dilation and tend to be young, middle-aged females without a histo ry of alcohol abuse. Non-entericcoated pancreati c enzymes preparations may be ll seful for the treatment of pain whereas enter ic-coated enzyme preparations are mo re useful for steatorrhea. Gastric acid can inactive the enzymes, particularly lipase, in non-enteric-coated preparations. Therefore, acid suppressive therapy is often required in conjunction with uncoated preparati o ns for maximum effectiveness

Q15 A 45-year-old woman with a long history of smoking and

alcohol abuse presents with a 6-month history of constant disabling abdominal pain. She has multiple calcifications on abdominal films, and MRCP reveals a dilated pancreatic duct with multiple strictures and stones. An EUS confirms a dilated pancreatic duct of 9 mm, plentiful calcifications,and fibrosis, especially in the head of the pancreatic head. Which of the following represents the most effective treatment strategy?

A. High doses of non-enteric-coated pancreatic enzymes with a PPI

B. ERCI' with stone removal andstenting C. Frey or Beger procedure withpancreatic head resection

andpancreaticoj ejunostomy D. Lateral pancreaticojejunostomy(Puestow procedure)

A15 ANSWER:D CRITIQUE Non-enteric-coated pancreatic enzymes might be effect ive,

especially in patients with early small duct disease, but are not believed to be effective in pain comrol in alcohoUc pancreatitis. In this patient with advanced disease and severe symptoms, enZ)lme supplements alone are unlikely to prove effective in controlling pain. ERCP with remova l of duct stones, stenting, dilat ion, and endotherapy is an opti on but in a patient with multiple strictures and stones is li kely to be unsuccessful. Furthermore, EUS showed that the pancreatic head was extensively di seased. Total pancreatectomy would be a last resort given the extent of the operation and the brittle diabetes that often results. Thus, in this otherwise healthy woman, operative decompression and drainage of the pancrea tic duct is a more attractive option and would likely res ul t in improvement in her pa in and narcotic requirement. The Frey procedure consists of a coring out of the head of the pancreas plus a pancreaticojejunostomy. Since she has considerable disease in the head, this patient is more likely to benefit from a Frey procedure than from a standardlateral pancreaticojejunostomy

A16 A 55-year-old man with a rustory of alcohol abuse and

chronic pancreatitis presents with an upper-GJ bleed requiring a transfusion of G units of packed cells. 1 Upper endoscopy reveals large gastric varices and duodenal erosions. Abdominal CT scanning shows gallstones in the gallbladder and multiple pancreatic calcifications with an enlarged spleen. The splenic vein appears occluded. Which of the following represents the most appropriate treatment?

A. Splenectomy B. Transjugular intrahepatic portosystemic shunt (TIPS)

procedure C. Glue injection into the gastric varices (obturation) D. Aggressive beta blockade

A16 ANSWER: A CRITIQUE The splenic vein meanders along the

posterior surface of the pancreas, where it can be affected by pancreatic inflammation that may lead to thrombosis. Chronic pancreatitis is an important ca use of noncirrhotic varices secondary to splenic vein thrombosis. The diagnosis of splenic vein thrombosis can be made by contrast-enhanced abdominal CT scanning or Doppler ultrasonography. Doppler ultrasound has a low sensitivity for splenic vein thrombosis, and if that is strongly suspected, a contrast CT or MR angiography is recommended. Splenectomy is usually curative. The other options would not be appropriate

Q17 A 60-year-old man with a history of chronic pancreatitis and

alcohol abuse presents with gradually increasing jaundice over 2 months and 2 weeks of pruritus. He is found to have an elevated bilirubin to G mg/dl (4 .5 mg/dl direct) and a threefold increase in the alkaline phosphatase. A CT scan shows pancreatic calcifications and dilation of the bile ducts and pancreatic ducts at the level of the head of the pancreas without a mass. A diagnosis of biliary obstruction secondary to chronic pancreatitis is made. Which of the following represents the best option?

A. ERCP with balloon dilation and placement of multiple plastic stents

B. ERCP with placement of a covered self-expanding metal stents

C. Roux-en-Y choledochojejunostomy D. ERCP with placement of an uncovered self-expanding

metal stent

A 17 ANSWER:C CRITIQUE ERCP with serial dilations and stenting is an effective therapy for benign

bile duct strictures, but in chronic pancreatitis only 25-50% respond. This poor response is presumably because of the differing pathogenesis between biliary strictures associated with chronic pancreatitis and postoperative strictures. In chronic pancreatitis, fibrotic tissue and calcification in the pancreatic head surrounds the bile ductj in the latter, only the duct wall is fibrotic. ERCP with placement of an uncovered self-expanding metal stent has been attempted; however, universal stent occlusion due to epithelial hyperplasia limits this approach. There has been some favorable experience regarding placement of fully covered self-expanding metal stents in patients with chronic pancreatitis-related common bile duct strictures, which is an off-label use in the United States. Unlike uncovered selfexpanding metal stents, it is usually possible to remove covered stems from the duct after several months. In preliminary studies there has been a significant complication rate with both stent placement and removal. Additional prospective studies with newer versions of covered metal stents are underway. The gold standard and most appropriate treatment in a patient who is a good surgical candidate remains a biliary enteric bypass . Of note, pancreatic cancer should be strongly suspected in any patient with chronic pancreatitis presenting with obstructive jaundice, even in the absence of a mass lesion on CT scan, and an EUS should be performed

A18 In patients with chronic pancreatitis with obstruction of

the main pancreatic duct by stones and or strictures that is thought to ca use pain, which of the following represents the most effective long-term management strategy?

A. Repeated endoscopic (ERCP) procedures with extra corporeal shock wave lithotripsy (ESWL), stone extraction, and stenting

B. Lateral pancreaticojejunostomy C. Placement of a self-expanding metal stent in the

pancreatic duct D. Uncoated pancreatic enzyme preparations

A 18 ANSWER:B CRITIQUE A randomized controlled study

comparing endoscopic therapy (ESWL, stone extraction, and srenting) to latera l pancreaticojejunostomy found surgical decompression to be more effective than endoscopic therapy in terms of longterm pain relief and symptomatic improvement. Metallic stent placement is contraindicated in the pancreatic duct. Pancreatic enzymes are unlikely to be helpful for pain relief in patients with disease that is this advanced