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Middle-aged Woman With Abdominal Pain, Jaundice, and Anorexia

Article

For 3 weeks, a 52-year-old woman has had right-sided, intermittent, dullabdominal pain and jaundice; these symptoms have worsened in the past fewdays. The pain radiates to the back, worsens with movement, is somewhatrelieved in certain positions, and is unrelated to eating or defecation. Duringthe past 3 weeks, she has also noticed darkening of her urine, a profound decreasein appetite, and an increase in fatigue; she has lost considerable weightbut is unsure of the exact amount. She has had no nausea, vomiting, or melenaor other change in her bowel movements.

For 3 weeks, a 52-year-old woman has had right-sided, intermittent, dull abdominal pain and jaundice; these symptoms have worsened in the past few days. The pain radiates to the back, worsens with movement, is somewhat relieved in certain positions, and is unrelated to eating or defecation. During the past 3 weeks, she has also noticed darkening of her urine, a profound decrease in appetite, and an increase in fatigue; she has lost considerable weight but is unsure of the exact amount. She has had no nausea, vomiting, or melena or other change in her bowel movements.

HISTORY
Several weeks earlier, hepatitis C was diagnosed by enzyme-linked immunosorbent assay. Other than this, she has had no major illnesses and takes no long-term medications. She has had a variety of minor surgeries, including hemorrhoid surgery and biopsy of a benign breast lump. She does not use tobacco, alcohol, or illicit drugs. Review of systems reveals pruritus that has coincided with her other symptoms-although she attributes it to her soap, because it has occurred after bathing.

PHYSICAL EXAMINATION
The patient is alert, oriented, and able to converse. Temperature is 37.1oC (98.8oF); heart rate, 112 beats per minute; oxygen saturation, 98% on room air; and blood pressure, 140/86 mm Hg. Sclerae and mucosae are deeply icteric. No lymph nodes are palpable in the neck or supraclavicular region. Chest is clear; no heart murmurs or gallops are noted. The abdomen is soft, with good bowel sounds, but it is diffusely tender in the upper region-more so on the right. Palpation reveals no masses or organ enlargement. Stool is heme-negative; no rectal masses are evident. Neurologic examination reveals no focal findings.

LABORATORY AND IMAGING RESULTS
Hemoglobin level is 11.3 g/dL. White blood cell count and electrolyte levels are normal. Albumin level is 2.9 g/dL. Total bilirubin level is 19.1 mg/dL; alkaline phosphatase, 608 U/L; alanine aminotransferase, 74 U/L; and aspartate aminotransferase, 67 U/L. A CT scan of the abdomen reveals dilated intrahepatic ducts, a dilated gallbladder, and probable duodenal wall inflammation- but no obvious gallstones.

Which of the following is the most appropriate next step?

A. Paracentesis with analysis of ascitic fluid.

B. Measurement of hepatitis C viral load titer.

C. Endoscopic retrograde cholangiopancreatography (ERCP).

D. Measurement of serum carcinoembryonic antigen (CEA) level.

CORRECT ANSWER: C
This patient has the worrisome clinical triad of cholestasis, abdominal pain, and weight loss, which always suggests hepatobiliary or pancreatic malignancy. The differential diagnosis also includes biliary tract stone disease and sclerosing cholangitis. Hepatitis C does not usually cause jaundice of this degree so quickly; pronounced jaundice is usually seen late in the natural history of hepatitis C, when cirrhosis and/or hepatocellular dysfunction has developed. The diagnosis in this woman was recent, and she has little clinical or laboratory evidence of advanced disease; her transaminase levels are not markedly elevated. Thus, her jaundice is obstructive. A thorough investigation of the nature (by genotype) and extent (by viral load [choice B] and/or biopsy) of her hepatitis C is a secondary consideration here. Paracentesis of ascites with cell counts and cytologic analysis (choice A) can be helpful in patients with decompensated cirrhosis (by revealing elevated polymorphonuclear cell counts and spontaneous bacterial peritonitis) and in those in whom hepatoma is suspected. However, this procedure is not indicated here-again because this woman’s syndrome is relatively acute and not suggestive of either of these conditions. Moreover, no significant ascites was found either on physical examination (there was no shifting dullness or fluid wave) or on the CT examination. The primary method of diagnosis and treatment of many pancreatic and biliary diseases-especially those that produce obstructive jaundice, as seen here-is ERCP (choice C). This procedure can both diagnose and treat many diseases of the bile ducts, including gallstone disease and malignancy. Stones that may be overlooked with standard ultrasonography and CT are often detected-and effectively treated-with ERCP. ERCP has a major role in malignant biliary obstruction. Tissue diagnosis of cholangiocarcinoma based on cytology specimens from bile duct brushings or aspirated bile has a sensitivity of 75%.1Direct biopsy and tissue sampling techniques using ERCP have recently been developed that may increase this sensitivity.1 ERCP can also provide effective palliative therapy. The occluded duct can be stented, which relieves the jaundice, pruritus, and anorexia associated with malignant biliary obstruction. Newer metal stents remain open for an average of 19 months; they are a significant advance in the palliation of these cancers.2,3 A variety of tumor markers have been evaluated in the diagnosis of cholangiocarcinoma. However, none are sensitive or specific enough to provide an accurate diagnosis. Elevated CEA levels (choice D) are only 68% sensitive and 83% specific.2 The tumor marker carbohydrate antigen 19-9 (CA 19-9) may be slightly more accurate,4 and combining CEA and CA 19-9 levels into numerical indices has been proposed but remains investigational. These tumor markers are probably more useful in the assessment of treatment efficacy and in detection of disease recurrence.2,4

Outcome of this case. The patient underwent ERCP and a biliary duct mass was found, along with massive periportal and peripancreatic lymphadenopathy. Samples for biliary duct and bile duct cytology were obtained, and a metal stent was successfully placed. Over the next 5 days, her pruritus resolved and her bilirubin level quickly fell; the level was 4.9 mg/dL at discharge. The cytology specimens were reported as stage V cholangiocarcinoma. Endoscopic ultrasonography showed the tumor to be nonresectable. The patient is currently in the care of an oncologist.

References:

REFERENCES:


1.

Brugge WR, Van Dam J. Pancreatic and biliary endoscopy.

N Engl J Med.

1999;341:1808-1816.

2.

deGroen PC, Gores GJ, LaRusso NF, et al. Biliary tract cancers.

N Engl J Med.

1999;341:1368-1378.

3.

Baron TH. Expandable metal stents for the treatment of cancerous obstructionof the gastrointestinal tract.

N Engl J Med.

2001;344:1681-1687.

4.

Nichols JC, Gores GJ, LaRusso NF, et al. Diagnostic role of serum CA 19-9for cholangiocarcinoma in patients with primary sclerosing cholangitis.

MayoClin Proc.

1993;68:874-879.

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