Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (124 page)

Carcinoma of the stomach should always be searched for by periodic prophylactic screening in high-risk patients, especially those with PA, gastric atrophy, or gastric polyps.
Cytology
: Exfoliative cytology positive in 80% of patients; false-positive result in <2%.

Tumor markers
: Increased serum CEA (>5 ng/dL) in 40–50% of patients with metastases and 10–20% of patients with surgically resectable disease. May be useful for postoperative monitoring for recurrence or to estimate metastatic tumor burden. Increased serum AFP and CA 19-9 in 30% of patients, usually incurable. Markers are not useful for early detection.

Gastric analysis
: Normal in 25% of patients. Hypochlorhydria in 25% of patients. Achlorhydria following histamine or betazole in 50% of patients.

Core laboratory
: Anemia due to chronic blood loss. Occult blood in stool.

DISORDERS OF THE PANCREAS

CARCINOMA OF THE PANCREAS

BODY OR TAIL

   Laboratory Findings

Imaging studies
: Most useful tests are ultrasound or CT scanning followed by 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. Declines to normal in 3–6 months if cancer is completely removed so may be useful for prognosis and followup. Detects tumor recurrence 2–20 weeks before clinical evidence. Not specific for 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-
¹³¹
I test demonstrates pancreatic duct obstruction with absence of lipase in the intestine, causing flat blood curves and increased stool excretion.

HEAD (SEE JAUNDICE)

The abnormal pancreatic function tests and increased tumor markers that occur with carcinoma of the body of the pancreas may be evident.

   Laboratory Findings

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 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.

CYSTIC FIBROSIS OF THE PANCREAS

Core laboratory
: Hypochloremic metabolic alkalosis and hypokalemia. Serum protein electrophoresis shows increasing IgG and IgA with progressive pulmonary disease; IgM and IgD are not appreciably increased. Serum albumin is often decreased (because of hemodilution due to cor pulmonale; may be found before cardiac involvement is clinically apparent). Serum chloride, sodium, potassium, calcium, and phosphorus are normal unless complications occur (e.g., chronic pulmonary disease with accumulation of CO
₂
; massive salt loss due to sweating may cause hyponatremia). Urine electrolytes are normal. Excessive loss of electrolytes in sweat and stool. Impaired glucose intolerance in approximately 40% of patients with glycosuria, and hyperglycemia in 8% precedes DM. Protein–calorie malnutrition, hypoproteinemia; fat malabsorption with vitamin deficiency. Stool and duodenal fluid show lack of trypsin digestion of x-ray film gelatin; useful screening test up to age 4; decreased chymotrypsin production.

Saliva findings
: Submaxillary saliva is more turbid, with increased calcium, total protein, amylase, chloride, and sodium but not potassium. These changes are not generally found in parotid saliva.

Other findings
: Overt liver disease, including cirrhosis, fatty liver, bile duct strictures, and cholelithiasis, in ≤5% of cases. Meconium ileus during early infancy. Chronic or acute and recurrent pancreatitis. Pancreatic insufficiency frequency by age 1 >90%; in adults >95%. Increased incidence of GI tract cancers. GU tract abnormalities with aspermia in 98% due to obstructive changes in the vas deferens and epididymis are confirmed by testicular biopsy.

MACROAMYLASEMIA IN VIVO ARTIFACT

   Definition

Complex of amylase with IgA, IgG, or other high molecular weight plasma proteins that cannot filter through the glomerulus due to its large size associated with no specific symptoms or disease states.

   Laboratory Findings

Core laboratory
: Serum lipase is normal; normal pancreatic-to-salivary amylase ratio. Urine amylase normal or low. Serum amylase
persistently
increased (often 1–4× normal) without apparent cause. Amylase–creatinine clearance ratio <1% with normal renal function is very useful for this diagnosis; should make the clinician suspect this diagnosis. Macroamylase is identified in serum by special gel filtration or ultracentrifugation technique.

   Limitations

   Macroamylase may be found in approximately 1% of randomly selected patients and 2.5% of persons with increased serum amylase level. Same findings may also occur in patients with normal molecular weight hyperamylasemia in which excess amylase is principally salivary gland isoamylase types 2 and 3.