Benign Pancreatic disorders

Raika Jamali M.D.Gastroenterologist and Hepatologist

Sina HospitalTehran University of Medical Sciences

Regulation of Pancreatic Secretion

• Gastric acid is the stimulus for the release of secretin from the duodenum, which stimulates the secretion of water and electrolytes from pancreatic ductal cells.

• Release of cholecystokinin (CCK) from the duodenum and proximal jejunum is largely triggered by long-chain fatty acids, certain essential amino acids (tryptophan, phenylalanine, valine, methionine), and gastric acid itself. CCK evokes an enzyme-rich secretion from acinar cells in the pancreas.

• The parasympathetic nervous system (via the vagus nerve) exerts significant control over pancreatic secretion.

• Secretion evoked by secretin and CCK depends on permissive roles of vagal afferent and efferent pathways.

• Also, vagal stimulation effects the release of vasoactive intestinal peptide (VIP), a secretin agonist.

• Pancreatic exocrine secretion is influenced by inhibitory neuropeptides:

– somatostatin, – pancreatic polypeptide,– peptide YY, – neuropeptide Y, – calcitonin gene–related peptides,

• Although pancreatic polypeptide and peptide YY may act primarily on nerves outside the pancreas, somatostatin acts at multiple sites.

• The mechanism of action of these various factors has not been fully defined.

– pancreastatin, – enkephalin,– glucagon, – galanin.

• The ductal cells secrete bicarbonate, derived from plasma (93%) and intracellular metabolism (7%).

• Bicarbonate enters through the sodium bicarbonate cotransporter with depolarization caused by chloride efflux through the cystic fibrosis transmembrane conductance regulator (CFTR).

• Secretin and VIP, both of which increase intracellular cyclic AMP, act on the ductal cells opening the CFTR in promoting secretion.

• CCK potentiates the stimulatory effects of secretin.

• Acetylcholine also plays an important role in ductal cell secretion.

• Bicarbonate helps neutralize gastric acid and creates the appropriate pH for the activity of pancreatic enzyme.

• All pancreatic enzymes have pH optima in the alkaline range.

• The acinar cell is concerned with the secretion of pancreatic enzymes.

• Proteins synthesized by the endoplasmic reticulum are processed in the Golgi and then targeted to the appropriate site, whether that be zymogen granules, lysosomes, or other cell compartments.

• The pancreas secretes amylolytic, lipolytic, and proteolytic enzymes.

• Amylolytic enzymes such as amylase, hydrolyze starch to oligosaccharides and to the disaccharide maltose.

• Lipolytic enzymes include:– lipase, – phospholipase A2,

– cholesterol esterase.

• Bile salts inhibit lipase in isolation, but colipase, another constituent of pancreatic secretion, binds to lipase and prevents this inhibition.

• Bile salts activate phospholipase A and cholesterol esterase.

• Proteolytic enzymes include:– endopeptidases (trypsin, chymotrypsin), which act on internal peptide bonds of

proteins;– exopeptidases (carboxypeptidases, aminopeptidases), which act on the free carboxyl-

and amino-terminal ends of peptides, respectively;– elastase.

• The proteolytic enzymes are secreted as inactive precursors and packaged as zymogens.

• Enterokinase, an enzyme found in the duodenal mucosa, cleaves the lysine-isoleucine bond of trypsinogen to form trypsin.

• Trypsin then activates the other proteolytic zymogens in a cascade phenomenon.

• The neurologic stimulation is cholinergic by the vagus nerve.

• The stimulatory neurotransmitters are acetylcholine and gastrin-releasing peptides.

• These neurotransmitters activate calcium-dependent second messenger systems, resulting in the release of zymogen granules.

• VIP is present in intrapancreatic nerves and potentiates the effect of acetylcholine.

Autodigestion of the pancreas• Prevented by the packaging of pancreatic proteases in

precursor form and by the synthesis of protease inhibitor [i.e., pancreatic secretory trypsin inhibitor (PSTI) or SPINK1], which can bind and inactivate about 20% of trypsin activity.

• These protease inhibitors are found in:– the acinar cell, – the pancreatic secretions, – the α 1 and α 2 globulin fractions of plasma.

• Loss of any of these protective mechanisms leads to zymogen activation, autodigestion, and acute pancreatitis.

Enteropancreatic Axis and Feedback Inhibition

• Pancreatic enzyme secretion is controlled, by a negative feedback mechanism induced by active serine proteases in the duodenum.

• To illustrate, perfusion of the duodenal lumen with phenylalanine causes a prompt result in increased plasma CCK levels as well as increased secretion of pancreatic enzymes.

Acute pancreatitis

• varies from interstitial pancreatitis, which is usually a mild and self-limited disorder, to necrotizing pancreatitis, in which the extent of pancreatic necrosis may correlate with the severity of the attack and its systemic manifestations.

Interstitial pancreatitis

Necrotizing pancreatitis

Etiology

• Common Causes – Gallstones (including microlithiasis)– Alcohol (acute and chronic alcoholism)– Hypertriglyceridemia– Endoscopic retrograde cholangiopancreatography (ERCP),

especially after biliary manometry– Trauma (especially blunt abdominal trauma)– Postoperative (abdominal and nonabdominal operations)– Drugs (azathioprine, 6-mercaptopurine, sulfonamides,

estrogens, tetracycline, valproic acid, anti-HIV medications)– Sphincter of Oddi dysfunction

Etiology

• Uncommon Causes – Vascular causes and vasculitis (ischemic-hypoperfusion states after

cardiac surgery)– Connective tissue disorders – Thrombotic thrombocytopenic purpura (TTP)– Cancer of the pancreas– Hypercalcemia– Periampullary diverticulum– Pancreas divisum– Hereditary pancreatitis– Cystic fibrosis– Renal failure

Etiology• Rare Causes

– Infections (mumps, coxsackievirus, cytomegalovirus, echovirus, parasites)– Autoimmune (e.g., Sjögren's syndrome)

• Causes to Consider in Patients with Recurrent Bouts of Acute Pancreatitis without an Obvious Etiology – Occult disease of the biliary tree or pancreatic ducts, especially microlithiasis,

sludge– Drugs– Hypertriglyceridemia– Pancreas divisum– Pancreatic cancer– Sphincter of Oddi dysfunction– Cystic fibrosis– Idiopathic

Pathogenesis• Autodigestion is a currently accepted pathogenic

theory; • Pancreatitis results when proteolytic enzymes are

activated in the pancreas rather than in the intestinal lumen.

• A number of factors (e.g., endotoxins, exotoxins, viral infections, ischemia, anoxia, lysosomal calcium, and direct trauma) are believed to facilitate activation of trypsin.

• Activated proteolytic enzymes, especially trypsin, not only digest pancreatic and peripancreatic tissues but also can activate other enzymes,(such as elastase and phospholipase A2).

Activation of Pancreatic Enzymes

• The initial phase is characterized by intrapancreatic digestive enzyme activation and acinar cell injury.

• Trypsin activation appears to be mediated by lysosomal hydrolases such as cathepsin B that become colocalized with digestive enzymes in intracellular organelles;

• it is currently believed that acinar cell injury is the consequence of trypsin activation.

• The second phase of pancreatitis involves the activation, chemoattraction, and sequestration of leukocytes and macrophages in the pancreas, resulting in an enhanced intrapancreatic inflammatory reaction.

• The third phase of pancreatitis is due to the effects of cytokines, released by the inflamed pancreas, on distant organs.

ColipaseElastaseChymotrypsinPhospholipase A2Xanthynedehydrogenase

KallycreinC3aC5aPlasminogenXIIa Factor

Systemic circulation

Alfa2 + Trypsin

Alfa2-M

RESLiverSpleenBone marrowNodes

Clearance

ProcolipaseProelastase

ChymotrypsinogenProphospholipase A2

Xanthynedehydrogenase

ProkallycreinC3C5PlasminogenXII Factor

Kininogens

Kinins

Trypsinogen

Trypsin

Trypsin

PSTI + Trypsin

PSTI

Alfa1-AT + Trypsin

Alfa1-AT

MesotrypsinEnzyme Y

• Activated proteolytic enzymes, especially trypsin, activate other enzymes such as elastase and phospholipase A2.

• The active enzymes and cytokines then digest cellular membranes and cause:– proteolysis, – edema, – interstitial hemorrhage,– vascular damage, – coagulation necrosis, – fat necrosis, – and parenchymal cell necrosis.

• Cellular injury and death result in the liberation of bradykinin, vasoactive substances, and histamine that can produce vasodilation, increased vascular permeability, and edema with profound effects on many organs.

• The systemic inflammatory response syndrome (SIRS) and acute respiratory distress syndrome (ARDS) as well as multiorgan failure may occur as a result of this cascade of local as well as distant effects.

Acute Pancreatitis

Complications: •Vascular leakage•Hypovolemia•Shock•ARDS•Acute renal tubular necrosis

IL-1 TNF

N.O. PAF

IL-6

IL-8

Other leucocyte productsOxygen radicalsElastaseIFN-α,γIL-10IL-2

• There appear to be a number of genetic factors that can increase the susceptibility and/or modify the severity of pancreatic injury in acute pancreatitis.

• Four susceptibility genes have been identified: – (1) cationic trypsinogen mutations (PRSS1m, R122Hm, and

N291), – (2) pancreatic secretory trypsin inhibitor (SPINK1),– (3) CFTR, – (4) monocyte chemotactic protein (MCP-1).

• Experimental and clinical data indicate that MCP-1 may be an important inflammatory mediator in the early pathologic process of acute pancreatitis, a determinant of the severity of the inflammatory response, and a promoter of organ failure.

Approach to the Patient

• Abdominal pain, vary from a mild and tolerable discomfort and more commonly to severe, constant, and incapacitating distress. is steady and boring.

• Is located in the epigastrium and periumbilical region and often radiates to the back as well as to the chest, flanks, and lower abdomen.

• More intense when the patient is supine, and patients may obtain some relief by sitting with the trunk flexed and knees drawn up.

•

• Nausea, vomiting, and abdominal distention due to gastric and intestinal hypomotility and chemical peritonitis are also frequent complaints.

Physical examination• A distressed and anxious patient. • Low-grade fever, • Tachycardia, • Hypotension. • Shock

– (1) hypovolemia secondary to exudation of blood and plasma proteins into the retroperitoneal space and a "retroperitoneal burn" due to activated proteolytic enzymes;

– (2) increased formation and release of kinin peptides, which cause vasodilation and increased vascular permeability; and

– (3) systemic effects of proteolytic and lipolytic enzymes released into the circulation.

• Jaundice occurs infrequently; when present, it usually is due to edema of the head of the pancreas with compression of the intrapancreatic portion of the common bile duct.

• Erythematous skin nodules due to subcutaneous fat necrosis may occur.

• There are pulmonary findings(In 10–20% of patients), including:– Basilar rales, – Atelectasis, – Pleural effusion, (frequently left sided)

• Abdominal tenderness and muscle rigidity• Diminished bowel sounds• An enlarged pancreas with walled off necrosis or a

pseudocyst may be palpable in the upper abdomen later in the disease course

• A faint blue discoloration around the umbilicus (Cullen's sign) may occur as the result of hemoperitoneum,

• Blue-red-purple or green-brown discoloration of the flanks (Turner's sign) reflects tissue catabolism of hemoglobin.

• Grey Turner sign • Cullen’s sign

Laboratory Data• Increased level of serum amylase and lipase. Values

threefold or more above normal virtually clinch the diagnosis if gut perforation, ischemia, and infarction are excluded.

• No correlation between the severity of pancreatitis and the degree of lipase and amylase elevations.

• After three to seven days, total serum amylase values tend to return toward normal.

• Pancreatic isoamylase and lipase levels may remain elevated for 7 to 14 days

Markers of Severity within 24 Hours

• SIRS [temperature >38° or < 36°C, Pulse > 90, Tachypnea > 24, WBC > 12,000]

• Hemoconcentration (Hct >44%) • BISAP (bedside index of severity in acute pancreatitis)

– (B) Blood urea nitrogen (BUN) >22 mg% – (I) Impaired mental status – (S) SIRS: 2/4 present – (A) Age >60 years – (P) Pleural effusion

• Organ Failure – Cardiovascular: systolic BP <90 mmHg, heartrate >130 – Pulmonary: Pao2 <60 mmHg

– Renal: serum creatinine >2.0 mg%– Gastrointestinal: bleeding >500 mL/24 hours

Severity

• Risk Factors– Age > 60 years – Obesity, BMI > 30 – Comorbid disease

• Markers during Hospitalization – Persistent organ failure – Pancreatic necrosis – Hospital-acquired infection

Laboratory Data• Leukocytosis (15,000–20,000 leukocytes per L)• Hemoconcentration

– with hematocrit values >44% – and/or blood urea nitrogen (BUN) level >22 mg/Dl

• Hyperglycemia – decreased insulin release,– increased glucagon release,– increased output of adrenal glucocorticoids and

catecholamines.

• Hypocalcemia

Laboratory Data• Hyperbilirubinemia (>4.0 mg/dL) in 10%

– is transient– return to normal in four to seven days.

• Serum alkaline phosphatase • and aspartate aminotransferase levels are also

transiently elevated• Elevated serum lactic dehydrogenase levels (>500

U/dL)• Hypertriglyceridemia occurs in 5–10%

• Hypoxemia (arterial Po2 60 mmHg), which may herald the onset of ARDS.

• Electrocardiogram is occasionally abnormal in acute pancreatitis with ST-segment and T-wave abnormalities simulating myocardial ischemia.

CT Findings and Grading of Acute Pancreatitis [CT Severity Index (Ctsi)]

Grade Findings Score

A Normal pancreas: normal size, sharply defined, smooth contour, homogeneous enhancement, retroperitoneal

peripancreatic fat without enhancement

0

B Focal or diffuse enlargement of the pancreas, contour may show irregularity, enhancement may be inhomogeneous but there is no peripancreatic

inflammation

1

C Peripancreatic inflammation with intrinsic pancreatic abnormalities

2

D Intrapancreatic or extrapancreatic fluid collections 3

E Two or more large collections or gas in the pancreas or retroperitoneum

4

Necrosis score based on contrast-enhanced CT

Necrosis (%) Score

0 0

<33% 2

33-50% 4

>50% 6

CT severity index equals unenhanced CT score plus necrosis score; 6 = severe disease.

CT Scan of acute pancreatitis

• CT showssignificantswellingand inflammationof the pancreas

Gall stone pancreatitis by ERCP

Diagnosis

• Requires two of the following: – typical abdominal pain, – threefold or greater elevation in serum amylase

and/or lipase level, – and/or confirmatory findings on cross-sectional

abdominal imaging.

Differential diagnosis • (1) perforated viscus, especially peptic ulcer• (2) acute cholecystitis and biliary colic• (3) acute intestinal obstruction• (4) mesenteric vascular occlusion• (5) renal colic• (6) myocardial infarction• (7) dissecting aortic aneurysm• (8) connective tissue disorders with vasculitis• (9) pneumonia• (10) diabetic ketoacidosis.

Local complications

• Necrosis– Sterile – Infected – Walled-off necrosis

• Pancreatic fluid collections– Pancreatic abscess – Pancreatic pseudocyst

• Pain • Rupture • Hemorrhage • Infection

Local complications• Obstruction of gastrointestinal tract (stomach,

duodenum, colon)• Pancreatic ascites

– Disruption of main pancreatic duct – Leaking pseudocyst

• Involvement of contiguous organs by necrotizing pancreatitis– Massive intraperitoneal hemorrhage – Thrombosis of blood vessels (splenic vein, portal vein) – Bowel infarction

• Obstructive jaundice

Systemic complications

• Pulmonary– Pleural effusion – Atelectasis – Mediastinal abscess – Pneumonitis – Acute respiratory distress syndrome

• Cardiovascular– Hypotension – Hypovolemia – Sudden death – Nonspecific ST-T changes in electrocardiogram simulating myocardial

infarction

• Pericardial effusion

Systemic complications

• Hematologic– Disseminated intravascular coagulation

• Gastrointestinal hemorrhage– Peptic ulcer disease – Erosive gastritis – Hemorrhagic pancreatic necrosis with erosion into major blood vessels – Portal vein thrombosis, variceal hemorrhage

• Renal– Oliguria – Azotemia – Renal artery and/or renal vein thrombosis – Acute tubular necrosis

Systemic complications• Metabolic

– Hyperglycemia – Hypertriglyceridemia – Hypocalcemia

• Encephalopathy – Sudden blindness (Purtscher's retinopathy)– Central nervous system– Psychosis

• Fat emboli– Fat necrosis– Subcutaneous tissues (erythematous nodules) – Bone – Miscellaneous (mediastinum, pleura, nervous system)

Mild Acute Pancreatitis• The majority of patients • No organ failure or only transient organ failure• Will respond to simple supportive care :

– bowel rest, – intravenous hydration with crystalloid– analgesia.

• Oral intake can be resumed once the patient is:– essentially pain free – has no nausea or vomiting, – normal bowel sounds, – and is hungry.

• Typically, a clear liquid diet has been recommended for the initial meal,

• but a low-fat solid diet is a reasonable choice following recovery

• Patients with gallstone pancreatitis are at increased risk of recurrence.

• Therefore, laparoscopic cholecystectomy during the same admission is recommended.

• An alternative for patients who are not surgical candidates would be to perform an endoscopic biliary sphincterotomy.

Severe Acute Pancreatitis

• Vigorous fluid resuscitation take place. • Measurement of hematocrit and BUN every

12 hours is recommended to ensure adequacy of fluid resuscitation.

• A decrease in hematocrit and BUN during the first 12 to 24 hours is strong evidence that sufficient fluids are being administered

• Patients with persistent organ failure that does not respond to increased fluids and/or nasal oxygen to overcome hypoxemia as well as those patients with labored respirations that may herald respiratory failure should be transferred to an intensive care unit for aggressive hydration and close monitoring for the possible need of intubation with mechanical ventilation, hemodialysis, and support of blood pressure.

Chronic Pancreatitis and

Pancreatic Exocrine Insufficiency

Pathophysiology

• Irreversible damage to the pancreas as distinct from the reversible changes noted in acute pancreatitis.

• The presence of histologic abnormalities:– chronic inflammation,– fibrosis, – progressive destruction of both exocrine and

eventually endocrine tissue

Tigar-O Classification System

• Toxic-metabolic– Alcoholic – Tobacco smoking – Hypercalcemia – Hyperlipidemia – Chronic renal failure – Medications—phenacetin abuse – Toxins—organotin compounds (e.g., DBTC)

• Idiopathic– Early onset – Late onset – Tropical

Tigar-O Classification System

• Genetic– Hereditary pancreatitis – Cationic trypsinogen – PRSS1

– PRSS2

– CFTR mutations – SPINK1 mutations

• Autoimmune– Isolated autoimmune chronic pancreatitis – Autoimmune chronic pancreatitis associated with Sjögren's syndrome – Inflammatory bowel disease – Primary biliary cirrhosis

Tigar-O Classification System

• Recurrent and Severe Acute Pancreatitis– Postnecrotic (severe acute pancreatitis) – Recurrent acute pancreatitis – Vascular diseases/ischemia – Postirradiation

• Obstructive– Pancreas divisum – Sphincter of Oddi disorders (controversial) – Duct obstruction (e.g., tumor) – Preampullary duodenal wall cysts – Posttraumatic pancreatic duct scars

• Alcohol has a direct toxic effect on the pancreas.

• While patients with alcohol-induced pancreatitis generally consume large amounts of alcohol, some consume as little as 50 g/d.

• Prolonged consumption of socially acceptable amounts of alcohol is compatible with the development of chronic pancreatitis.

• Cigarette smoke leads to an increased susceptibility to pancreatic self-digestion and predisposes to dysregulation of duct cell CFTR function.

• It has become increasingly apparent that smoking is an independent, dose-dependent risk factor.

• Pancreatic stellate cells (PSC) are believed to play a role in maintaining normal pancreatic architecture that can shift toward fibrogenesis in the case of chronic pancreatitis

• Alcohol or additional stimuli lead to matrix metalloproteinase–mediated destruction of normal collagen in pancreatic parenchyma, which later allows for pancreatic remodeling.

• Proinflammatory cytokines (TNFα, ILB-1, IL-6) as well as oxidant complexes are able to induce PSC activity with subsequent new collagen synthesis.

• PSCs also possess transforming growth factor B–mediated self-activating autocrine pathways that may explain disease progression in chronic pancreatitis even after removal of noxious stimuli.

Etiologic Considerations

• Alcoholism is the most common cause of clinically apparent chronic pancreatitis,

• While cystic fibrosis is the most frequent cause

in children

• Idiopathic chronic pancreatitis. – up to 15% of patients with idiopathic pancreatitis

may have pancreatitis due to genetic defects

Hereditary chronic pancreatitis

• Gene encoding for trypsinogen.

• The defect prevents the destruction of trypsinogen and allows it to be resistant to the effect of trypsin inhibitor, become spontaneously activated, and to remain activated.

• Mutations of CFTR.

• This gene functions as a cyclic AMP–regulated chloride channel.

• In patients with cystic fibrosis, the high concentration of macromolecules can block the pancreatic ducts

• 1000 putative mutations of the CFTR gene

Monosymptomatic form of cystic fibrosis (chronic pancreatitis)

• Patients were adults when the diagnosis of pancreatitis was made;

• None had any clinical evidence of pulmonary disease,

• Sweat test results were not diagnostic of cystic fibrosis.

• Combination of two CFTR mutations and an N34S SPINK1 mutation increased the risk of pancreatitis 900-fold

Autoimmune Pancreatitis

• Mild symptoms usually abdominal pain, but without frequent attacks of pancreatitis,

• Presentation with obstructive jaundice • Diffuse swelling and enlargement of the pancreas, especially

the head, the latter mimicking carcinoma of the pancreas • Diffuse irregular narrowing of the pancreatic duct in ERCP • Increased levels of serum gamma globulins especially IgG4 • Presence of other autoantibodies (ANA,RF) • Can occur with other autoimmune diseases: Sjögren's

syndrome, primary sclerosing cholangitis, ulcerative colitis, rheumatoid arthritis

Autoimmune Pancreatitis

• Extra pancreatic bile duct changes such as stricture of the common bile duct and intrahepatic ducts

• Absence of pancreatic calcifications or cysts • Pancreatic biopsies reveal extensive fibrosis and

lymphoplasmacytic infiltration • Glucocorticoids are effective in alleviating symptoms,

decreasing size of the pancreas, and reversing histopathologic changes

• Two-thirds of patients present with either obstructive jaundice or a "mass" in the head of the pancreas mimicking carcinoma

• AIP can be diagnosed with at least one of three abnormalities:

– (1) diagnostic histology;– (2) characteristic findings on CT and

pancreatography combined with elevated IgG4 levels;

– (3) response to glucocorticoid therapy

Clinical Features

• The abdominal pain may be quite variable in location, severity, and frequency.

• The pain can be constant or intermittent with frequent pain-free intervals.

• Eating may exacerbate the pain, leading to a fear of eating with consequent weight loss.

• The spectrum of abdominal pain ranges from mild to quite severe, with narcotic dependence as a frequent consequence

Clinical Features • Maldigestion is manifested as chronic diarrhea,

steatorrhea, weight loss, and fatigue. • Patients with chronic abdominal pain may or

may not progress to maldigestion, and 20% of patients will present with symptoms of maldigestion without a history of abdominal pain

• Despite the steatorrhea, clinically apparent deficiencies of fat-soluble vitamins are surprisingly uncommon.

Laboratory data• In contrast to acute pancreatitis, the serum

amylase and lipase levels are usually not strikingly elevated in chronic pancreatitis.

• Elevation of serum bilirubin and alkaline phosphatase may indicate cholestasis secondary to common bile duct stricture caused by chronic inflammation.

• Many patients have impaired glucose tolerance with elevated fasting blood glucose levels

Laboratory data

• Diagnostic test with the best sensitivity and specificity is the secretin stimulation test.

• It becomes abnormal when 60% of the pancreatic exocrine function has been lost.

• This usually correlates well with the onset of chronic abdominal pain.

Laboratory data

• Vitamin B12 malabsorption in 40%. This can be corrected by the administration of oral pancreatic enzymes.

• A decrease of fecal elastase level to <100 g per gram of stool strongly suggests severe pancreatic exocrine insufficiency.

Imaging studies• Diffuse calcifications noted on plain film of the

abdomen usually indicate significant damage

• CT may show calcification, dilated ducts, or an atrophic pancreas, pseudocyst and pancreatic cancer.

• MRCP provides a direct view of the pancreatic duct and is now the diagnostic procedure of choice.

What are arrows?

CT - chronic pancreatitis

MRCP

• Whether EUS alone can detect early, noncalcific chronic pancreatitis with the same degree of accuracy as the hormone-stimulation test is controversial.

• Data comparing these modalities head-to-head have indicated that EUS is not a sensitive enough test for detecting early chronic pancreatitis.

• However, recent data suggest that EUS can be combined with endoscopic pancreatic function testing (EUS-ePFT) during a single endoscopy to screen for chronic pancreatitis in patients with chronic abdominal pain.

Complications• Narcotic addiction• Impaired glucose tolerance• Gastroparesis• Cobalamin malabsorption• Nondiabetic retinopathy• Effusions with high amylase content • Gastrointestinal bleeding• Jaundice• Cholangitis and/or biliary cirrhosis• Subcutaneous fat necrosis• Bone pain• Pancreatic cancer

Annular Pancreas

• When the ventral pancreatic anlage fails to migrate correctly to make contact with the dorsal anlage, the result may be a ring of pancreatic tissue encircling the duodenum.

• Such an annular pancreas may cause intestinal obstruction in the neonate or the adult.

• Symptoms of postprandial fullness, epigastric pain, nausea, and vomiting may be present for years before the diagnosis is entertained.

• The radiographic findings are symmetric dilation of the proximal duodenum with bulging of the recesses on either side of the annular band, effacement but not destruction of the duodenal mucosa, accentuation of the findings in the right anterior oblique position, and lack of change on repeated examinations.

• The differential diagnosis should include duodenal webs, tumors of the pancreas or duodenum, postbulbar peptic ulcer, regional enteritis, and adhesions.

• Patients with annular pancreas have an increased incidence of pancreatitis and peptic ulcer.

Pancreas divisum

• Occurs when the embryologic ventral and dorsal pancreatic anlagen fail to fuse, so that pancreatic drainage is accomplished mainly through the accessory papilla.

• Is the most common congenital anatomic variant of the human pancreas.

• Does not predispose to the development of pancreatitis in the great majority of patients .

• However, the combination of pancreas divisum and a small accessory orifice could result in dorsal duct obstruction.

MRCP of pancreas divisum

Macroamylasemia

• Amylase circulates in the blood in a polymer form too large to be easily excreted by the kidney.

• Elevated serum amylase value, a low urinary amylase value, and a Cam/Ccr ratio of <1%.

• The presence of macroamylase can be documented by chromatography of the serum

• Documented in a few patients with cirrhosis or non-Hodgkin's lymphoma.