Several tests have proved of value in the evaluation of pancreatic disease. Examples of specific tests and their usefulness in the diagnosis of acute and chronic pancreatitis are summarized in Table 340-1 and Fig. 340-1. At some institutions, pancreatic function tests are available and performed if the diagnosis of chronic pancreatic disease remains a possibility after noninvasive tests (ultrasound, computed tomography [CT], magnetic resonance cholangiopancreatography [MRCP]) or invasive tests (endoscopic retrograde cholangiopancreatography [ERCP], endoscopic ultrasonography [EUS]) have given normal or inconclusive results. In this regard, tests using direct stimulation of the pancreas with secretin are the most sensitive.
TABLE 340-1Tests Useful in the Diagnosis of Acute and Chronic Pancreatitis and Pancreatic Tumors ||Download (.pdf) TABLE 340-1 Tests Useful in the Diagnosis of Acute and Chronic Pancreatitis and Pancreatic Tumors
|Test ||Principle ||Comment |
|Pancreatic Enzymes in Body Fluids |
|Serum lipase ||Pancreatic inflammation leads to increased serum enzyme levels ||Enzyme measurement of choice for diagnosis of acute pancreatitis |
|Amylase || || |
|1. Serum ||Pancreatic inflammation leads to increased serum enzyme levels ||Simple; reliable if test results are three times the upper limit of normal (3× ULN) |
|2. Urine ||Renal clearance of amylase is increased in acute pancreatitis ||Infrequently used |
|3. Ascitic fluid ||Disruption of gland or main pancreatic duct leads to increased amylase concentration ||Can help establish source of ascites; false positives occur with intestinal obstruction and perforated ulcer; can also measure lipase |
|4. Pleural fluid ||Exudative pleural effusion with pancreatitis ||False positives occur with carcinoma of the lung and esophageal perforation |
|Studies Pertaining to Pancreatic Structure |
|Radiologic and radionuclide tests |
|1. Plain film of the abdomen ||Can be abnormal in acute and chronic pancreatitis ||Infrequently used |
|2. Upper gastrointestinal x-rays || ||Infrequently used |
|3. Ultrasonography (US) ||Can provide information on edema, inflammation, calcification, pseudocysts, and mass lesions ||Simple, noninvasive; sequential studies quite feasible; useful in diagnosis of gallstones; pancreas visualization limited by interference from overlying bowel gas |
|4. Computed tomography (CT) scan ||Permits detailed visualization of pancreas and surrounding structures, pancreatic fluid collection, pseudocyst; assessment of necrosis or interstitial disease ||Useful in the diagnosis of pancreatic calcification, dilated pancreatic ducts, and pancreatic tumors; may not be able to distinguish between inflammatory and neoplastic mass lesions |
|5. Magnetic resonance cholangiopancreatography (MRCP) ||Three-dimensional imaging has been used to produce very good images of the pancreatic-biliary ductal system by a noninvasive technique ||Has replaced ERCP as a diagnostic test; noninvasive |
|6. Endoscopic ultrasonography (EUS) ||High-frequency transducer used with EUS can produce very high-resolution images and depict changes in the pancreatic duct and parenchyma with great detail ||Can be used to assess gallstones, chronic pancreatitis, and pancreatic carcinoma |
|7. Endoscopic retrograde cholangiopancreatography (ERCP) ||Cannulation of pancreatic and common bile duct permits visualization of pancreatic-biliary ductal system ||Primarily a therapeutic procedure; invasive |
|Pancreatic biopsy with US or CT guidance ||Percutaneous aspiration biopsy of mass-forming lesions of the pancreas ||High diagnostic yield; laparotomy avoided; can be done with EUS for the evaluation of chronic pancreatitis, autoimmune pancreatitis, and pancreatic carcinoma |
|Tests of Exocrine Pancreatic Function |
|Direct stimulation of the pancreas with analysis of duodenal contents |
|1. Secretin test ||Secretin leads to increased output of pancreatic juice and HCO3–; pancreatic secretory response is related to the functional mass of pancreatic tissue ||Sensitive enough to detect occult disease; involves duodenal intubation and fluoroscopic placement of gastroduodenal tube; poorly defined normal enzyme response; overlap in chronic pancreatitis; large secretory reserve capacity of the pancreas; currently done at only a few medical centers |
|2. Endoscopic secretin test ||Replaces need for tube placement duodenum ||Sensitive enough to detect occult disease; high negative predictive value; avoids intubation and fluoroscopy; requires sedation |
|Measurement of intraluminal digestion products |
|1. Quantitative stool fat determination ||Lack of lipolytic enzymes brings about impaired fat digestion ||Reliable reference standard for defining severity of malabsorption; does not distinguish between maldigestion and malabsorption |
|Measurement of pancreatic enzymes in feces |
|1. Fecal elastase ||Pancreatic secretion of proteolytic enzymes; not degraded in intestine ||Diagnostic accuracy best if value is <100 μg/g performed on a solid stool |
A stepwise diagnostic approach to the patient with suspected chronic pancreatitis (CP). Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography (sMRCP/MRCP) are appropriate diagnostic alternatives to endoscopic retrograde cholangiopancreatography (ERCP). CT, computed tomography.
Pancreatic Enzymes in Body Fluids
The serum amylase and lipase levels are widely used as screening tests for acute pancreatitis in the patient with acute abdominal pain or back pain. Values greater than three times the upper limit of normal (3× ULN) in combination with epigastric pain strongly suggest the diagnosis of acute pancreatitis. 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 unless there is pancreatic ductal disruption, ductal obstruction, or pseudocyst formation. Approximately 85% of patients with acute pancreatitis have a threefold or greater elevated serum lipase and amylase levels. The values may be normal if (1) there is a delay (2–5 days) before blood samples are obtained, (2) the underlying disorder is chronic pancreatitis rather than acute pancreatitis, or (3) hypertriglyceridemia is present. Patients with hypertriglyceridemia and pancreatitis have been found to have spuriously low levels of amylase and perhaps lipase activity. 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.
The serum amylase can be elevated in other conditions (Table 340-2), 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, breast, and ovary). Isoamylase determinations do not accurately distinguish elevated blood amylase levels from pancreatic or nonpancreatic sources. In patients with unexplained hyperamylasemia, measurement of macroamylase can avoid numerous tests in patients with this rare disorder.
TABLE 340-2Causes of Hyperamylasemia and Hyperamylasuria ||Download (.pdf) TABLE 340-2 Causes of Hyperamylasemia and Hyperamylasuria
|Pancreatic Disease |
Chronic: ductal obstruction
Complications of pancreatitis
Ascites caused by pancreatic duct disruption
|Non-Pancreatic Disorders |
Salivary gland lesions
Carcinoma of the lung, esophagus, breast, or ovary
|Other Abdominal Disorders |
Biliary tract disease: cholecystitis, choledocholithiasis
Perforated or penetrating peptic ulcer
Intestinal obstruction or inflammation
Ruptured ectopic pregnancy
Elevation of ascitic fluid amylase occurs in acute pancreatitis as well as in (1) ascites due to disruption of the main pancreatic duct 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 pancreatitis, chronic pancreatitis, carcinoma of the lung, and esophageal perforation. 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 dysfunction only when creatinine clearance was <0.8 mL/s (<50 mL/min). In such patients, the serum amylase level was invariably <500 IU/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.
Studies Pertaining to Pancreatic Structure
Plain films of the abdomen, which once provided useful information in patients with acute and chronic pancreatitis, have been superseded by other more detailed imaging procedures (ultrasound, EUS, CT, MRCP).
Ultrasonography can provide important information in patients with acute pancreatitis, chronic pancreatitis, pseudocysts, and pancreatic carcinoma. Sonographic changes can indicate the presence of edema, inflammation, and calcification (not obvious on plain films of the abdomen), as well as pseudocysts, mass lesions, and gallstones. In acute pancreatitis, the pancreas is characteristically enlarged. In pancreatic pseudocyst, the usual appearance is primarily that of a smooth, round fluid collection. Pancreatic carcinoma distorts the usual landmarks, and mass lesions >3.0 cm are usually detected as localized, solid lesions. US is often the initial investigation for most patients with suspected pancreatic disease. However, obesity and excess intestinal bowel gas can interfere with pancreatic imaging by US studies.
Computed tomography is the best imaging study for initial evaluation of a suspected pancreatic disorder 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 (see Chap. 341, Figs. 341-1, 341-2, and 341-4), and pancreatic neoplasms. Acute pancreatitis is characterized by (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. 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. Dynamic CT (using rapid IV administration of contrast) is useful in estimating the extent of pancreatic necrosis and in predicting morbidity and mortality. CT provides clear images much more rapidly and essentially negates artifact caused by patient movement. If acute pancreatitis is confirmed with serology and physical examination findings, CT scan in the first 3 days is not recommended to avoid overuse and minimize costs. The major benefit of CT in acute pancreatitis is the diagnosis of pancreatic necrosis in patients not responding to conservative management within 72 h.
Endoscopic ultrasonography produces high-resolution images of the pancreatic parenchyma and pancreatic duct with a transducer fixed to an endoscope that can be directed onto the surface of the pancreas through the stomach or duodenum. EUS and MRCP have replaced ERCP for diagnostic purposes. EUS allows one to obtain information about the pancreatic duct as well as the parenchyma and 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. EUS has been studied as a diagnostic modality for chronic pancreatitis. Criteria for abnormalities on EUS in severe chronic pancreatic disease have been developed. There is general agreement that the presence of five or more of the nine criteria listed in Table 340-3 is highly predictive of chronic pancreatitis. 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. The exact role of EUS versus CT, ERCP, or function testing in the early diagnosis of chronic pancreatitis has yet to be clearly defined.
TABLE 340-3Endoscopic Ultrasonographic Criteria for Chronic Pancreatitis (Total Criteria = 9) ||Download (.pdf) TABLE 340-3 Endoscopic Ultrasonographic Criteria for Chronic Pancreatitis (Total Criteria = 9)
|Ductal ||Parenchymal |
|Stones ||Echogenic strands |
|Hyperechoic main duct margins ||Echogenic foci |
|Main duct irregularity ||Lobular contour |
|Main duct dilatation ||Cyst |
|Visible side branches || |
MRI and MRCP are now being used to view the bile ducts, pancreatic duct, and the pancreas parenchyma in both acute pancreatitis and chronic pancreatitis. For diagnostic imaging in chronic pancreatitis, non-breath-holding and three-dimensional turbo spin-echo techniques are being used to produce superb MRCP images. 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 visualized in a normal pancreas. Secretin-enhanced MRCP is emerging as a method to better evaluate ductal changes. 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.
As mentioned, EUS and MRCP have largely replaced ERCP in the diagnostic evaluation of pancreatic disease. As these techniques become more refined, especially with the administration of secretin, they may well be the diagnostic tests of choice to evaluate the pancreatic duct. ERCP is 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 (see Chap. 341, Fig. 341-1). Pancreatic carcinoma is characterized by stenosis or obstruction of either the pancreatic duct or the common bile duct; both ductal systems are often abnormal (double-duct sign). In chronic pancreatitis, ERCP abnormalities in the main pancreatic duct and side branches have been outlined by the Cambridge classification. The presence of ductal stenosis and irregularity can make it difficult to distinguish chronic pancreatitis from carcinoma. 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). Elevated serum amylase levels after ERCP have been reported in the majority of patients, and clinical pancreatitis in 5–10% of patients. Recent data suggest that pancreatic duct stenting and rectal indomethacin can decrease the incidence of ERCP-induced pancreatitis. ERCP should not be done for diagnostic purposes and should especially be avoided in high-risk patients.
PANCREATIC BIOPSY WITH RADIOLOGIC GUIDANCE
Percutaneous aspiration biopsy or a trucut biopsy of a pancreatic mass often distinguishes a pancreatic inflammatory mass from a pancreatic neoplasm.