Imaging studies: Most useful tests are ultrasound or CT scanning followed by endoscopic retrograde cholangiopancreatography (ERCP) (at which time fluid is also obtained for cytologic and pancreatic function studies). This combination will correctly diagnose or rule out cancer of the pancreas in ≥90% of cases. ERCP with brush cytology has S/S = ≤25%/≤100%. Radioisotope scanning of the pancreas may be done (⁷⁵Se) for lesions >2 cm.

Histology: Ultrasound-guided needle biopsy has reported sensitivity of 80-90%; false positives are rare.

Tumor markers: Serum markers for tumor (CA 19-9, CEA, and so on) are often normal. In carcinoma of the pancreas, CA 19-9 has S/S = 70%/87%, PPV = 59%, and NPV = 92%; there is no difference in sensitivity between local disease and metastatic disease. Often normal in early stages, they are not useful for screening. Increased values may help differentiate benign disease from cancer. It declines to normal in 3-6 months if cancer is completely removed, so it may be useful for prognosis and follow-up. It detects tumor recurrence 2-20 weeks before clinical evidence. It is not specific for the pancreas because high levels may also occur in other GI cancers, especially those affecting the colon and bile
duct. CEA level in bile (obtained by percutaneous transhepatic drainage) was reported increased in 76% of a small group of cases.

Testosterone: Dihydrotestosterone ratio <5 (normal approximately 10) in >70% of men with pancreatic cancer (due to increased conversion by tumor); less sensitive but more specific than CA 19-9 and present in higher proportion of stage I tumors.

Serum amylase and lipase: May be slightly increased in early stages (<10% of cases); with later destruction of the pancreas, they are normal or decreased. They may increase following secretin-pancreozymin stimulation before destruction is extensive; therefore, the increase is less marked with a diabetic glucose tolerance curve. Serum amylase response is less reliable. See Serum Glycoprotein 2.

Glucose tolerance: Curve is of the diabetic type, with overt diabetes in 20% of patients with pancreatic cancer. Flat blood sugar curve with IV tolbutamide tolerance test indicates destruction of islet cell tissue. Unstable, insulin-sensitive diabetes that develops in an older man should arouse suspicion of carcinoma of the pancreas.

Serum LAP: Increased (>300 U) in 60% of patients with carcinoma of the pancreas due to liver metastases or biliary tract obstruction. It may also be increased in chronic liver disease.

Other: Triolein-¹³¹I test demonstrates pancreatic duct obstruction with absence of lipase in the intestine, causing flat blood curves and increased stool excretion.

Core laboratory: Serum bilirubin is increased (12-25 mg/dL), mostly conjugated (increase persistent and nonfluctuating). Serum ALP is increased. Both urine and stool urobilinogen are absent. Increased serum cholesterol (usually >300 mg/dL) with esters is not decreased. Other liver function tests are usually normal. See Serum Glycoprotein 2.

Hematology: Increased prothrombin time (PT); normal after IV vitamin K administration.

Other: Secretin-cholecystokinin stimulation evidences duct obstruction when duodenal intubation shows decreased volume of duodenal contents (<10 mL/10-minute collection period) with usually normal bicarbonate and enzyme levels in duodenal contents. Acinar destruction (as in pancreatitis) shows normal volume (20-30 mL/10-minute collection period), but bicarbonate and enzyme levels may be decreased. Abnormal volume, bicarbonate, or both are found in 60-80% of patients with pancreatitis or cancer. In carcinoma, the test result depends on the relative extent and combination of acinar destruction and of duct obstruction.

Histology: Cytologic examination of duodenal contents shows malignant cells in 40% of patients. Malignant cells may be found in up to 80% of patients with periampullary cancer.

Lipase: Serum lipase increases within 3-6 hours with peak at 24 hours and usually returns to normal over a period of 8-14 days, is superior to amylase, increases to a greater extent, and may remain elevated for up to 14 days after amylase returns to normal. In patients with signs of acute pancreatitis, pancreatitis is highly likely (clinical specificity = 85%) when lipase ≥5× upper reference limit (URL), if values change significantly with time, and if amylase and lipase changes are concordant. (Lipase should always be determined whenever amylase is determined.) Urinary lipase is not clinically useful. It has been suggested that a lipase-amylase ratio >3 (and especially >5) indicates alcoholic rather than nonalcoholic pancreatitis. If lipase ≥5× URL, acute pancreatitis or organ rejection is highly likely but unlikely if <3× URL (Figure 7-1).

Amylase: Increase begins in 3-6 hours, rises rapidly within 8 hours in 75% of patients, reaches maximum in 20-30 hours, and may persist for 48-72 hours; there is >95% sensitivity during the first 12-24 hours. The increase may be ≤40× normal, but the height of the increase and rate of fall do not correlate with the severity of the disease, prognosis, or rate of resolution. In patients with signs of acute pancreatitis, amylase >3× ULN or >600 Somogyi units/dL is very suggestive of acute pancreatitis. An increase >7-10 days suggests an associated cancer of the pancreas or pseudocyst, pancreatic ascites, or nonpancreatic etiology. Similar high values may occur in obstruction of the
pancreatic duct; they tend to fall after several days; ≤19% of patients with acute pancreatitis (especially when seen more than 2 days after onset of symptoms) may have normal values, especially with an alcoholic etiology and longer duration of symptoms, even when dying of acute pancreatitis. It may also be normal in relapsing chronic pancreatitis and patients with hypertriglyceridemia (technical interference with test). It is frequently normal in acute alcoholic pancreatitis. Acute abdomen due to GI infarction or perforation rather than acute pancreatitis is suggested by only moderate increase in serum amylase and lipase (<3× URL) and evidence of bacteremia. Of patients with acute alcoholic intoxication, 10-40% have elevated serum amylase (about half are salivary type); they often present with abdominal pain, but increased serum amylase is usually <3× URL. Levels >25× URL indicate metastatic tumor rather than pancreatitis. Serum pancreatic isoamylase can distinguish elevations due to salivary amylase that may account for 25% of all elevated values. (In healthy persons, 40% of total serum amylase is pancreatic type and 60% is salivary type.) Only slight increase in serum amylase and lipase values suggests a different diagnosis than acute pancreatitis. Many drugs increase both amylase and lipase in serum.

Increased urinary amylase tends to reflect serum changes by a time lag of 6-10 hours, but sometimes, increased urine levels are higher and of longer duration than serum levels. The 24-hour level may be normal even when some of the 1-hour specimens show increased values. Amylase levels in hourly samples of urine may be useful. Ratio of amylase clearance to creatinine clearance is increased (>5%) and avoids the problem of timed urine specimens and also increased in any condition that decreases tubular reabsorption of amylase (e.g., severe burns, DKA, chronic renal insufficiency, multiple myeloma, acute duodenal perforation). It is considered not specific and now discouraged by some but still recommended by others.

Calcium: Serum level is decreased in severe cases 1-9 days after onset (due to binding to soaps in fat necrosis). The decrease usually occurs after amylase and lipase levels have become normal. Tetany may occur. (Rule out hyperparathyroidism if serum calcium is high or fails to fall in hyperamylasemia of acute pancreatitis.)

Bilirubin: Serum levels may be increased when pancreatitis is of biliary tract origin but is usually normal in alcoholic pancreatitis. Serum ALP, ALT, and AST may increase and parallel serum bilirubin rather than amylase, lipase, or calcium levels. Marked amylase increase (e.g., >2,000 U/L) also favors biliary tract origin. Fluctuation >50% in 24 hours of serum bilirubin, ALP, ALT, and AST suggests intermittent biliary obstruction.

Trypsin: Serum level is increased. High sensitivity makes a normal value useful for excluding acute pancreatitis. But low specificity (increased in large proportion of patients with hepatobiliary, bowel, and other diseases and renal insufficiency; increased in 13% of patients with chronic pancreatitis, 50% with pancreatic carcinoma) and RIA technology limit utility.

C-reactive protein (CRP): Level peaks 3 days after onset of pain; at 48 hours, sensitivity = 65-100% and PPV = 37-77%. Level of 150 mg/L distinguishes mild from severe disease.

Laboratory criteria for severe disease or predictor of mortality:

Laboratory findings due to predisposing conditions (may be multiple):

Laboratory findings due to complications:

Laboratory findings are often normal.

Imaging studies: CT, ultrasound, and ERCP are most accurate for diagnosing and staging chronic pancreatitis. Radioactive scanning of the pancreas (selenium) yields variable findings in different clinics.

Cholecystokinin-secretin test: Measures the effect of IV administration of cholecystokinin and secretin on volume, bicarbonate concentration, and amylase output of duodenal contents and increase in serum lipase and amylase. This is the most sensitive and reliable test (gold standard) for chronic pancreatitis especially in the early stages. However, it is technically difficult and is often not performed accurately; gastric contamination must be avoided. Some abnormality occurs in >85% of patients with chronic pancreatitis. Amylase output is the most frequent abnormality. When all three are abnormal, there is a greater frequency of abnormality in the tests listed below.

Serum pancreolauryl test: Fluorescein dilaurate with breakfast is acted on by a pancreas-specific cholesterol ester hydrolase-releasing fluorescein, which is absorbed from the gut and measured in serum, preceded by administration of secretin, and followed by metoclopramide. Reported S/S = 82%/91%.

Glucose tolerance test (GTT): In 65% of patients with chronic pancreatitis and frank diabetes in >10% of patients with chronic relapsing pancreatitis. When GTT is normal in the presence of steatorrhea, the cause should be sought elsewhere than in the pancreas.

Laboratory findings due to malabsorption: Occurs when >90% of exocrine function is lost.

Laboratory findings due to chronic pancreatitis and pancreatic exocrine insufficiency: