Chapter 370 - Approach to the Patient with Pancreatic Disease

Question 1

Name the most common causes of pancreatitis.

Answer 1

“Although it is well-appreciated that pancreatitis is frequently secondary to biliary tract disease and alcohol abuse, it can also be caused by drugs, genetic mutations, trauma, and viral infections and is associated with metabolic and connective tissue disorders.”

Question 2

How frequently is the etiology of pancreatitis obscure?

Answer 2

“In ~30% of patients with acute pancreatitis and 25-40% of patients with chronic pancreatitis, the etiology initially can be obscure.”

Question 3

Summarize the epidemiology of acute and chronic pancreatitis.

Answer 3

“The incidence of acute pancreatitis is about 5-35/100 000 new cases per yer wordlide, with a mortality rate of about 3%. The incidence of chronic pancreatitis is about 4-8 new cases per 100 000 per year with a prevalence of 26-42 cases per 100 000. The number of patients admitted to the hospital who suffer with both acute and chronic pancreatitis in the United State is largely increasing and is now estimated to be 274 119 for acute pancreatitis and 19 724 for chronic pancreatitis. Acute pancreatitis is now the most common gastrointestinal diagnosis requiring hospitalization in the United States. Acute and chronic pancreatic disease costs an estimated 3 billion dollars annually in health care expenditures. These numbers may underestimate the true incidence and prevalence, because non-alcohol-induced pancreatitis has been largely ignored.”

Question 4

What is the prevalence of chronic pancreatitis at autopsy?

Answer 4

0,04 to 5%.

Question 5

How does one explain the difficulty in diagnosing chronic pancreatitis? Which tests should one use and what are their respective advantages and limitations?

Answer 5

“The diagnosis of chronic pancreatitis, especially in mild disease, is hampered by the relative inaccessibility of the pancreas to direct examination and the nonspecificity of the abdominal pain associated with chronic pancreatitis. Many patients with chronic pancreatitis do not have elevated blood amylase or lipase levels. Some patients with chronic pancreatitis develop signs and symptoms of pancreatic exocrine insufficiency, and thus, objective evidence for pancreatic disease can be demonstrated. However, there is a very large reservoir of pancreatic exocrine function. More than 90% of the pancreas mus be damage before maldigestion of fat and protein is manifested. Noninvasive, indirect tests of pancreatic exocrine function (fecal elastase) are much more likely to give abnormal results in patients with obvious advanced pancreatic disease (i.e., pancreatic calcification, steatorrhea, or diabetes mellitus) than in patients with occult disease. Invasive, direct tests of pancreatic secretory function (secretin tests) are the most sensitive and specific tests to detect early chronic pancreatic disease when imaging is equivocal or normal.”

Question 6

What is the usefulness of secretin tests?

Answer 6

When noninvasive and/or invasive imaging tests have given normal or inconclusive results, “tests using direct stimulation of the pancreas with secretin are the most sensitive.”

Question 7

Explain the usefulness of plasmatic amylase and lipase levels and their progression over the course of acute and chronic pancreatitis.

Answer 7

“Values greater than three times the upper limit of normal in combination with epigastric pain strongly suggests the diagnosis if gut perforation or infarction is excluded. In acute pancreatitis, the serum amylase and lipase are usually elevated within 24 h of onset and remain so for 3-7 days. Levels usually return to normal within 7 days”

“In the absence of objective evidence of pancreatitis by abdominal ultrasound, CT scan, MRCP, or EUS, mild to moderate elevations of amylase and/or lipase are not helpful in making a diagnosis of chronic pancreatitis.”

Question 8

In which situations should one expect a high level of amylase/lipase that goes beyond the 7 days window in acute pancreatitis?

Answer 8

“Levels usually return to normal within 7 days unless there is pancreatic ductal disruption, ductal obstruction, or pseudocyst formation.”

Question 9

Name the causes for normal plasmatic amylase/lipase levels during the course of pancreatitis.

Answer 9

(1) there is a delay (of 2-5 days) before blood samples are obtained;
(2) the underlying disorder is chronic pancreatitis rather than acute pancreatitis;
(3) Hypertrigliceridemia is present.

Question 10

Which organs might be responsible for amylase production and, in doing so, which conditions might be responsible for hyperamilasemia other than pancreatitis?

Answer 10

“The serum amylase can be elevated in other conditions, in part because the enzyme is found in many organs. In addition to the pancreas and salivary glands, small quantities of amylase are found in the tissues of the fallopian tubes, lung, thyroid, and tonsils and can be produced by various tumors (carcinomas of the lung, esophagus, breat, and ovary).”

Question 11

Isoamylase determination accurately distinguishes amylase elevation due to pancreatitis from other nonpancreatic causes.
True or False?

Answer 11

False.

Question 12

Which rare diagnosis should be searched in a patient with unnexplained hyperamylasemia?

Answer 12

Macroamylasemia.

Question 13

What is the meaning of elevated amylase on ascitic or pleural fluid?

Answer 13

“Elevation of ascitic fluid amylase occurs in acute pancreatitis as well as in (1) ascitis due to disruption of the main pancreatic dusct or a leaking pseudocyst and (2) other abdominal disorders that simulate pancreatitis (e.g., intestinal obstruction, intestinal infarction, or perforated peptic ulcer). Elevation of pleural fluid amylase can occur in acute pancreatites, chronic pancreatitis, carcinoma of the lung, and esophageal perforation.”

Question 14

Amylase determination is better than lipase determination in patients with renal failure.
True or False?

Answer 14

False.
“Lipase is the single best enzyme to measure for the diagnosis of acute pancreatitis. No single blood test is reliable for the diagnosis of acute pancreatitis in patients with renal failure. Pancreatic enzyme elevations are usually less than three times the upper limit of normal. Determining whether a patient with renal failure and abdominal pain has pancreatitis remains a difficult clinical problem. One study found that serum amylase levels were elevated in patients with renal dyfcuntion only when creatinine clearance was less than 0,8mL/s (less than 50mL/min). In such patients, the serum amylase level was invariably less than 500IU/L in the absence of objective evidence of acute pancreatitis. In that study, serum lipase and trypsin levels paralleled serum amylase values. With these limitations in mind, the recommended screening test for acute pancreatitis in renal disease is serum lipase.”

Question 15

How does one differentiate the features of pancreatic pseudocysts from pancreatic tumors and mass lesions?

Answer 15

“In pancreatic pseudocyst, the usual appearance is primarily that of smooth, round fluid collection. Pancreatic carcinoma distorts the usual landmarks, and mass lesions >3,0 cm are usually detected as localized, solid lesions.”

Question 16

Which factors might limit the use of ultrasonography (US) as the initial study for pancreatic disease?

Answer 16

“US is often the initial investigation for most patients with suspected pancreatic disease. However, obesity and excess small- and large-bowel gas can interfere with pancreatic imaging by US studies.”

Question 17

Compare computed tomography (CT) to ultrasonography (US) in the study of pancreatic disease.

Answer 17

“Computed tomography (CT) is the best imaging study for initial evaluation of a suspected pancreatic disroder and for the assessment of complications of acute and chronic pancreatitis. It is especially useful in the detection of pancreatic and peripancreatic acute fluid collections, fluid-containing lesions such as pseudocysts, walled-off necrosis, calcium deposits, and pancreatic neoplasms.”

Question 18

What are the feactures on computed tomography that favore an acute pancreatitis diagnosis?

Answer 18

“(1) enlargement of the pancreatic outline, (2) distortion of the pancreatic contour, and/or (3) a pancreatic fluid that has a different attenuation coefficient than normal pancreas.”

Question 19

Name the advantages of using the following contrast agents on CT-scan of pancreatic disease: (i) oral contrast; (ii) IV contrast.

Answer 19

(i) “oral, water-soluble contrast agents are used to opacify the stomach and duodenum during CT scans; this strategy permits more precise delineation of various organs as well as mass lesions.”
(ii) “Dynamic CT (using rapid IV administration of contrast) is useful in estimating the extent of pancreatic necrosis and in predicting morbidity and mortality.”

Question 20

CT scan should be used in the first 3 days if ultrasonography is normal or inconclusive regarding acute pancreatitis.
True or False?

Answer 20

False.

Question 21

Why is it that endoscopic ultrasonography (EUS) has largely replaced ERCP for diagnostic purposes in many centers, regarding a population with pancreatic disease?

Answer 21

“EUS allows one to obtain information about the pancreatic duct as well as the parenchyma nd has few procedure-related complications associated with it, in contrast to the 5-10% of post-ERCP pancreatitis observed. EUS is also helpful in detecting common bile duct stones in acute pancreatitis. Pancreatic masses can also be biopsied via EUs in cases with suspected pancreas cancer, and one can deliver nerve-blocking agents through EUS fine-needle injection in patients suffering from pancreatic pain from chronic pancreatitis or cancer.”

Question 22

Endocopisc ultrasonography and ERCP are similar to secretin testing in detecting early changes of chronic pancreatitis.
True or False?

Answer 22

True.
“Recent studies comparing EUS and ERCP to the secretin test in patients with unexplained abdominal pain suspected of having chronic pancreatitis show similar diagnostic accuracy in detecting early changes of chronic pancreatitis.”

Question 23

What are the limitations of magnetic resonance cholangiopancreatography (MRCP) in chronic pancreatitis?

Answer 23

“The main pancreatic duct and common bile duct can be seen well, but there is still a question as to whether changes can be detected consistently in the secondary ducts. The secondary ducts are not visualizaed in a normal pancreas.”

Question 24

Explain the role of T1 and T2 imaging magnetic resonance cholangiopancreatography (MRCP) in evaluating complications due to acute pancreatitis.

Answer 24

“In anteroposterior imaging, T2 imaging of fluid collections can differentiate necrotic debris from fluid in suspected walled-off necrosis, and T1 imaging can diagnose hemorrhage in suspected pseudoaneurysm rupture.”

Question 25

What is the role of endoscopic retrograde cholangiopancreatography (ERCP) in pancreatic disease?

Answer 25

“ERCP os primarily of therapeutic value after CT, eUS , or MRCP has detected abnormalities requiring invasive endoscopic treatment. ERCP can also be helpful at clarification of equivocal findings discovered with other imaging techniques.”

Question 26

What is the double-duct sign?

Answer 26

“Pancreatic carcinoma is characterized by stenosis or obstruction of either the pancreatic duct or the common bile duct; both ducstal systems are often abnormal (double-duct sign).”

Question 27

Cambridge classification is used to diagnose chronic pancreatitis using ERCP abnormalities findings.
True or False?

Answer 27

True.

Question 28

What is the effect of aging on biliary and pancreatic ducts?

Answer 28

“It is important to be aware that ERCP changes interpreted as indicating chronic pancreatitis actually may be due to the effects of aging on the pancreatic duct or sequelae of a recent attack of acute pancreatitis. Although aging may cause impressive ductal alterations, it does not affect the results of pancreatic function tests (i.e., the secretin test).”

Question 29

ERCP-induced pancreatitis occurs in 5-10% of patients. Is there any procedures to prevent this complication?

Answer 29

“Recent data suggests that pancreatic duct stenting and rectal indomethacin can decrease the incidence of ERCP-induced pancreatitis. ERCP should rarely be done for diagnostic purposes and should especially be avoided in high-risk patients.”

Question 30

Name the two tests of exocrine pancreatic function.

Answer 30

1. Direct stimulation of the pancreas by IV infusion of secretin followed by collection and measurement of duodenal contents.
2. Measurement of fecal pancreatic enzymes such as elastase.

Question 31

How should one interpret the secretin test?

Answer 31

“The secretin test, used to detect diffuse pancreatic disease, is based on the physiologic principle that the pancreatic secretory response is directly related to the functional mass of pancreatic tissue. In the standard assay, secretin is given IV in a dose of 0,2ug/Kg of synthetic human secretin as a bolus. Normal valuves for the standard secretin test are (1) volume output >2mL/Kg per hour, (2) bicarbonate (HCO3-) concentration >80mmol/L, and (3) HCO3- output >10mmol/L in 1 h. The most reproducible measurement, giving the highest level of discrimination between normal subjects and patients with chronic pancreatic exocrine insufficiency, appears to be the maximal bicarbonate concentration. A cutoff point below 80mmol/L is considered abnormal and suggestive of abnormal secretory function that is most commonly observed in early chronic pancreatitis.”

“It must be emphasized that an abnormal secretin test suggests only that chronic pancreatic damage is present.”

Question 32

Why is it that secretin test might detect chronic pancreatic lesion earlier than the measurement of fecal pancreatic enzymes?

Answer 32

“There may be a dissociation between the results of the secretin test and other tests of absorptive function. For example, patients with chronic pancreatitis often have abnormally low outputs of HCO3- after secretin but have normal fecal fat excretion. Thus the secretin test measures the secretory capacity of ductular epithelium, whereas fecal fat excretion indirectly reflects intraluminal lipolytic activity. Steatorrhea does not occur until intraluminal levels of lipase are markedly reduced, underscoring the fact that only small amounts of enzymes are necessary for intraluminal digestive activities.”

Question 33

How should one interpret the elastase-1 activity levels in stool?

Answer 33

“Decreased elastase-1 activity (FE-1) in stoll is an excellent test to detect severe pancreatic exocrine insufficiency (PEI) in patients with chronic pancreatitis and cystic fibrosis. FE-1 levels less than 200μg/g are normal; levels of 100-200μg/g are considered mild, and levels less than 100μg/g are severe for PEI. Although the test is simples and noninvasive, it can give false-positive results and has a low sensitivity. Fecal levels less than 50μg/g are definitive for PEi provided that the stool specimen is solid.”