Biliary Disease Differential Diagnoses

Updated: May 02, 2018
  • Author: Annie T Chemmanur, MD; Chief Editor: BS Anand, MD  more...
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DDx

Diagnostic Considerations

Important considerations

Choose the procedure that is appropriate for the patient. Know the limitations of the procedure. The presence of dense adhesions, advanced liver disease, unexpected cancer, or a severely inflamed gallbladder or encountering troublesome bleeding should prompt assessment of the need to convert a laparoscopic cholecystectomy to an open procedure.

Special concerns

Postcholecystectomy syndrome

The persistence, recurrence, or development of pain following the removal of the gallbladder is referred to as the postcholecystectomy syndrome. It occurs in 10%-15% of the 600,000 cholecystectomies performed annually in the United States.

A retained common duct stone can be identified in 0.3%-18% of cases. A history of recurrent biliary-type pain associated with nausea, vomiting, fever, and chills is suggestive of a retained common duct stone, and sonographic evidence of ductal dilation is supportive of this diagnosis. An intraoperative cholangiogram is very useful to exclude a retained common duct stone.

Biliary leaks or fistula occur in 0.1%-0.4% of all gallbladder operations. Leakage from the cystic duct stump is most common, but it may (1) emanate from accessory ducts along the gallbladder fossa, (2) be the result from an injury to a major extrahepatic duct, or (3) follow T-tube removal after open cholecystectomy and common bile duct exploration. In the past, these were associated with a mortality rate of about 30%.

Benign biliary strictures occur with a frequency of 0.1%-0.8% of all gallbladder operations. This usually is the result of an operative injury to the bile duct. The first type results from a surgical misadventure such as inadvertent duct ligation or placing clips on the bile duct. Only 10% of patients present with pain and jaundice in the first week, and another 60% present within 3 months of the surgery. The second type results either from ischemic injury or from crush injury from clamps. Many months or years may pass before mild cholestasis or symptoms develop when biliary sludge or stones form proximal to a stricture.

Cystic duct remnants are a rare and controversial cause of postcholecystectomy pain. The long cystic duct stump promotes bile stasis within which microlithiasis or stones may form. The passage of this material through the papilla is believed to cause intermittent biliary-type pain. In extremely rare instances, a neuroma or granuloma of the cystic duct stump can cause pain.

Sphincter of Oddi dysfunction

Sphincter of Oddi dysfunction is an uncommon, probably overdiagnosed, cause of biliary-type pain. The 2 subtypes are papillary stenosis and sphincter of Oddi dyskinesia. The former is a mechanical problem, and the latter is a functional problem.

Papillary stenosis is a mechanical problem involving an inflammatory stenosis of the duodenal papilla of Vater. It may be caused by choledocholithiasis, ascariasis, sclerosing cholangitis, pancreatitis, iatrogenic instrumentation of the duodenal papilla, peptic duodenitis, and Crohn disease involving the duodenum and cholesterolosis of the papilla. It is diagnosed manometrically when the sphincter of Oddi manometry reveals a basal sphincter pressure greater than 40 mm Hg that does not decrease in response to cholecystokinin (CCK) or amyl nitrate. It also may be diagnosed surgically via the inability to pass a #3 Bakes dilator through the sphincter or during endoscopic retrograde cholangiopancreatography (ERCP) via an inability to advance a 5F cannula retrograde over a wire placed into the bile duct.

Endoscopic sphincterotomy alleviates biliary-type pain in most, but not all, patients with papillary stenosis.

The term sphincter of Oddi dysfunction has been used to describe a clinical syndrome of biliary or pancreatic obstruction related to mechanical or functional abnormalities of the sphincter of Oddi.

Sphincter of Oddi dysfunction is diagnosed by a sphincter manometry study revealing a basal pressure greater than 40 mm Hg that is responsive to CCK or amyl nitrate. Other supportive features may include phasic wave contractions with a peak amplitude greater than 220 mm Hg, contraction duration greater than 8 seconds, and frequency of greater than 10 per minute. An increased percentage of retrograde contractions have also been cited. Abnormal sphincter motility is uncommon, identified in 1% of 454 patients following cholecystectomy; 14% of those were diagnosed with a postcholecystectomy syndrome.

HIV-associated cholangiopathy

Several biliary tract abnormalities are associated with human immunodeficiency virus (HIV) infection, but the CD4+ lymphocytes are usually below 100 cells per microliter before these problems develop. These include acalculous cholecystitis, papillary stenosis, and a sclerosing cholangitis–like picture. The causes include opportunistic infections, such as infection with cytomegalovirus, Cryptosporidium species, Enterocytozoon bieneusi, and Mycobacterium species, or neoplasms, such as Kaposi sarcoma and non-Hodgkin lymphoma. Liver-associated enzymes usually show a cholestatic picture, without significant hyperbilirubinemia, unless a neoplasm obstructs the bile duct. Medical therapy to date has been ineffective in treating opportunistic infections.

Ursodeoxycholic acid (UDCA) has been used in the treatment of primary sclerosing cholangitis, a disorder with similar intrahepatic changes to AIDS cholangiopathy. This observation has led to its experimental use in patients with acquired immunodeficiency syndrome (AIDS) cholangiopathy; results in a small number of patients have found an improvement in symptoms and a fall in the levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. The authors recommend giving UDCA in a dose 300 mg 3 times daily, primarily in patients who have intrahepatic ductal disease and markedly elevated liver function test results.

Vanishing bile duct syndrome

This is a rare syndrome affecting the intrahepatic bile ducts. Most patients are asymptomatic, but some may present with pruritus and, rarely, jaundice. The alkaline phosphatase level usually is elevated, along with gamma-glutamyltransferase (GGT), which may exceed 600 IU/L. Obtaining a wedge liver biopsy often is necessary to make the diagnosis. The cause of ductopenia may be related to developmental abnormalities of the intrahepatic biliary system, as in Alagille syndrome. On physical examination, frontal bossing and triangular facies may be noted, and tests that are more specific can reveal butterfly vertebrae and posterior embryotoxon of the eye. Progressive familial intrahepatic cholestasis is another type, caused by a genetic mutation of the membrane transporter for phospholipids (MDR3).

Other types are acquired and are associated with cystic fibrosis, systemic mastocytosis, histiocytosis-X, Hodgkin disease, and drug-induced hepatotoxicity. Patients without a clear association are diagnosed with idiopathic adult ductopenia.

Differential Diagnoses