Extrahepatic bile duct stricture and elevated CA 19-9: malignant or benign? (Case Report).

Abstract: Biliary obstruction due to a proximal bile duct stricture is commonly a result of cholangiocarcinoma. We describe a patient who began having intermittent episodes of jaundice 3 years after cholecystectomy. Despite endoscopic placement of a biliary stent and adequate biliary decompression, the serum CA 19-9 level remained elevated at 58 U/ml (normal <37 U/ml). Segmental bile duct resection and Roux-en-Y hepaticojejunostomy were done. The stricture was caused by a traumatic bile duct neuroma. Diagnostic and therapeutic considerations of this entity are discussed, with special emphasis on the value of noninvasive biliary imaging by magnetic resonance imaging (MRI), the utility and interpretation of the CA 19-9 level, and the role for resection or surgical biliary decompression.

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Obstructive jaundice due to a proximal bile duct stricture is rarely caused by a benign process, particularly in the absence of gallstones. (1,2) Biliary stenoses that are not accompanied by an obvious mass lesion frequently are difficult to diagnose, and malignant masquerade remains a problematic entity. (1) Under these circumstances, elevation of the biliary tumor marker CA 19-9 may aid in the diagnosis of cholangiocarcinoma and support an oncologic therapy approach that includes bile duct resection. (3) We report the case of a patient with jaundice, CA 19-9 elevation, and a proximal bile duct stricture due to a benign cause, and discuss its implications for the diagnostic and therapeutic approach to proximal bile duct strictures.

Case Report

A 65-year-old woman was seen because of a 7-year history of intermittent painless jaundice. She had had an uncomplicated open cholecystectomy 10 years earlier for symptomatic cholelithiasis. The first episode of jaundice occurred 3 years after the cholecystectomy and resolved spontaneously without specific treatment. After two additional episodes of jaundice, an endoscopic biliary stent was placed approximately 6 years after cholecystectomy. Liver biopsy at that time revealed no evidence of malignancy. Subsequently, two episodes of cholangitis necessitated biliary stent change.

At presentation, symptoms included intermittent mild right upper quadrant pain, which was self-limited and not associated with food intake. There was significant fatigue, but no weight loss, fever, or chills. Other aspects of the medical history were noncontributory. Physical examination revealed an afebrile, not jaundiced woman with no acute distress. The abdomen was soft and nontender, with a well-healed right upper quadrant incision, and no masses, ascites, or organomegaly. Complete blood count, electrolyte values, and coagulation profile were normal. Other laboratory values were total bilirubin 0.3 mg/dl, aspartate aminotransferase 38 U/L, alanine aminotransferase 45 U/L, alkaline phosphatase 191 U/L, carcinoembryonic antigen (CEA) <2.5 ng/ml, and CA 19-9 58 U/ml (normal, <37). Ultrasonography of the abdomen showed no evidence of cholelithiasis. Computed tomography of the abdomen revealed some intrahepatic and extrahepatic biliary dilation with a biliary stent in place, but no masses. Magnetic resonance i maging (MRI) of the abdomen with cholangiographic reconstruction showed an isolated stricture in the common hepatic duct close to the junction of the right and left hepatic ducts (Fig. 1), with moderate dilation of the common bile duct and cystic duct stump. The patient underwent laparotomy with segmental resection of the extrahepatic bile ducts, including the strictured area, and a Roux-en-Y hepaticojejunostomy reconstruction. The periductal connective tissue showed a prominent scar reaction, and the wall of the bile duct was diffusely thickened (Fig. 2). Bile culture isolates grew enterococci, Escherichia coli, Pseudomonas sp, and Klebsiella sp. Histopathologic analysis of the resected common hepatic duct revealed hypertrophic nerve tissue within the wall with numerous moderately thickened bundles of focally disorganized nerve branches characteristic of traumatic neuroma (Fig. 3). The patient tolerated the procedure well, was discharged after 1 week; and continued to be in good health more than 1 year after the operation.

Discussion

Obstructive jaundice due to a bile duct neuroma is a rare yet well-reported entity, with most descriptions in the form of case reports. (4-12) Characteristic for most symptomatic biliary neuromas is a history of previous cholecystectomy, with a symptom-free postoperative interval that can range from a few months to 35 years. (8) Aside from their causative role in mechanical bile duct obstruction, biliary neuromas have been implicated as a source for the pain of postcholecystectomy syndrome. (4,5) Although the mechanisms of neuroma formation are not completely understood, expression of acidic fibroblast growth factor (FGF) and FGF receptors has been shown, indicating a dysregulation of posttraumatic neuronal growth. (11) In our patient, too, a benign mechanism for biliary obstruction was suggested by the history of cholecystectomy and a long symptomatic interval without progressive symptoms or weight loss. The intermittent course with some spontaneous resolution of jaundice, the elevation of CA 19-9, and an ap parent ductal filling defect despite absence of a mass on MRI were unusual findings. Thus, we were not certain that a malignant mechanism could be safely excluded. For this reason, and because of the need to provide long-term biliary drainage without the risk of recurrent cholangitis, we recommended operative therapy. This patient's case invites discussion of two important aspects: the diagnostic approach to a biliary stricture in light of a possible malignancy, and the role of surgical treatment.

Benign bile duct strictures may result from trauma, local inflammation or infection, sclerosing cholangitis, or other mechanisms. (1, 2, 13-15) Unfortunately, many benign strictures present with some diagnostic features considered characteristic of malignancies and may mimic cancer. (1, 2, 14) The tumor marker CA 19-9 can be a useful indicator of upper gastrointestinal cancer, including cholangiocarcinoma. (16, 17) The magnitude of CA 19-9 elevation (>100 U/L is more predictive of cancer), and cholangitis or significant biliary obstruction are important modifiers that influence or limit its specificity and positive predictive value. (3, 16-18) In our patient, the relatively minor elevation of CA 19-9, combined with bacteriobilia and a normal CEA level, was not strongly suggestive of cancer. In addition, the long duration of symptoms and the intermittent exacerbations would be more supportive, though not entirely characteristic, of a benign process.

Endoscopic retrograde cholangiography and ductal brushing cytology are of limited value in the diagnosis of biliary strictures. (15, 18, 19) Noninvasive imaging techniques can provide important information, however. Intrahepatic bile duct dilation and a stricture longer than 14 mm are highly suggestive of malignancy. (19) Magnetic resonance cholangiography has a lower sensitivity (80%) but a high specificity (96%) for the diagnosis of a malignant bile duct structure. (20) A ductal wall mass may suggest a cancerous process. Recently, positron emission tomography has been used with success to delineate differences between benign and malignant biliary strictures, but experience with this modality is still limited. (18)

In view of these diagnostic challenges, therapeutic implications would seem to favor an aggressive approach, preferably resection and biliary reconstruction, to provide diagnostic information and address the long-term need for functional biliary drainage at the same time. For these reasons, we recommended an operative resectional approach in our patient, regardless of the ultimate nature of her biliary stricture. Outcome after resection generally is good, (14) and resection is preferred, though successful techniques for stricture repair (21) or extrahilar cholangioenteric bypass without resection have been described as well. (22) For biliary neuromas in particular, poor postoperative results have been correlated with a failure to excise. (8)

Whether biliary stents represent appropriate therapy in otherwise operable patients remains doubtful; aside from a possible diagnostic uncertainty, we would also be concerned about the associated risk of bacteriobilia and cholangitis in cases of bilioenteric stents. (23) In fact, removal of any stent and its duodenal connection is recommended if stricture resection is not possible and a biliary bypass is done. We conclude from the experience with our patient that the CA 19-9 level, endoscopic retrograde cholangiography, and stent placement were of no particular help to reach the recommendation for surgical therapy; diagnostic MRI and magnetic resonance cholangiography provided useful information for planning and conducting the resection.

Accepted January 14, 2002.

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RELATED ARTICLE: Key Points

* Biliary obstruction due to bile duct neuromas typically occurs after previous cholecystectomy.

* Proximal bile duct strictures can be imaged well with magnetic resonance cholangiography.

* Mild CA 19-9 elevation during jaundice or cholangitis is not necessarily indicative of cholangiocarcinoma.

* Endoscopic retrograde cholangiography and stenting of proximal bile duct strictures add little to diagnosis and management of the noninfected, operable patient.

* Bile duct resection and reconstruction may be indicated regardless of a benign or malignant stricture etiology.

From thc Departments of General Surgical Oncology and Anatomic Pathology, City of I-lope National Medical Center, Duane, CA.

Reprint requests to Roderich E. Schwarz, MD, PhD, Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Thc Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901. Email: [e-mail]

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