SEMINARS IN LIVER DISEASE-VOL.
1 1 , NO. 1 , 1991
Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) and cholangiocarcinoma are cholestatic diseases with different natural histories but all too frequently indistinguishable clinical presentations. This difficulty in distinguishing PSC from cholangiocarcinoma accounts for much of the controversy surrounding the association between these two entities. A typical example is that of a patient with a history of PSC for several years who presents with increasing jaundice and is found to have a cholangiocarcinoma. Some clinicians would contend that the patient had a cholangiocarcinoma all along which masqueraded as PSC. Another viewpoint is that the patient developed a cholangiocarcinoma in the setting of PSC. A hypothesis is that the chronic inflammatory process of PSC encourages malignant transformation of the biliary epithelium. This hypothesis is not unique; chronic inflammation caused by cholelithiasis' and Clonorchis sinensis' have been associated with carcinoma of the gallbladder and bile ducts. There is also clinical and pathologic evidence that supports an association between PSC and cholangiocarcinoma and suggests that PSC may be a premalignant condition. Herein, we will review the evidence supporting this unproven and highly controversial association and describe the clinical presentation, course, and management of patients thought to be afflicted with both entities.
PSC AND CHOLANGIOCARCINOMA An association between PSC and cholangiocarcinoma is suggested epidemiologically. Both entities share an established association with chronic ulcerative colitis. Liver disease has long been known to occur in patients with chronic ulcerative colitis. Indeed, histologic changes consistent with PSC, such as pericholangitis and interlobular hepatitis, were recognized in patients with chronic ulcerative colitis nearly 40 years ago.'.-' Clinically, these histologic findings were associated with a wide spectrum of signs and symptoms, ranging from the asymptomatic individual to intense jaundice and pruri-
From the Depcrrtment c$ General Surgery. Muyo Clinic, Ruchestrr, Minnesota Reprint requests: Dr. Rosen, Department of General Surgery, Mayo Clinic, Rochester, M N 55905
26
tus. With the advent of endoscopic retrograde cholangiography, the radiographic diagnosis of PSC was made more readily and an association between PSC and chronic ulcerative colitis became more apparent. Schrumpf et al' reported cholangiographic evidence of PSC in 19 of 336 patients (6%) with chronic ulcerative colitis. Conversely, approximately 70 to 80% of patients with PSC have chronic ulcerative colitis."-x Patients with chronic ulcerative colitis clearly have a predisposition to develop cholangiocarcinoma. Parker and Kendally reported a single patient with cholangiocarcinoma in an autopsy study of 39 livers from patients with chronic ulcerative colitis in 1954. Subsequently, many case report^""^ and several series"-18 have described cholangiocarcinoma in patients with chronic ulcerative colitis. Roberts-Thomson et al" observed four cases of cholangiocarcinoma in 292 chronic ulcerative colitis patients seen over a 14-year period, for a frequency of 1.4%. They estimated that the probability of both diseases occurring together by chance alone was extremely small (p
1 1 , NO. 1 , 1991
Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) and cholangiocarcinoma are cholestatic diseases with different natural histories but all too frequently indistinguishable clinical presentations. This difficulty in distinguishing PSC from cholangiocarcinoma accounts for much of the controversy surrounding the association between these two entities. A typical example is that of a patient with a history of PSC for several years who presents with increasing jaundice and is found to have a cholangiocarcinoma. Some clinicians would contend that the patient had a cholangiocarcinoma all along which masqueraded as PSC. Another viewpoint is that the patient developed a cholangiocarcinoma in the setting of PSC. A hypothesis is that the chronic inflammatory process of PSC encourages malignant transformation of the biliary epithelium. This hypothesis is not unique; chronic inflammation caused by cholelithiasis' and Clonorchis sinensis' have been associated with carcinoma of the gallbladder and bile ducts. There is also clinical and pathologic evidence that supports an association between PSC and cholangiocarcinoma and suggests that PSC may be a premalignant condition. Herein, we will review the evidence supporting this unproven and highly controversial association and describe the clinical presentation, course, and management of patients thought to be afflicted with both entities.
PSC AND CHOLANGIOCARCINOMA An association between PSC and cholangiocarcinoma is suggested epidemiologically. Both entities share an established association with chronic ulcerative colitis. Liver disease has long been known to occur in patients with chronic ulcerative colitis. Indeed, histologic changes consistent with PSC, such as pericholangitis and interlobular hepatitis, were recognized in patients with chronic ulcerative colitis nearly 40 years ago.'.-' Clinically, these histologic findings were associated with a wide spectrum of signs and symptoms, ranging from the asymptomatic individual to intense jaundice and pruri-
From the Depcrrtment c$ General Surgery. Muyo Clinic, Ruchestrr, Minnesota Reprint requests: Dr. Rosen, Department of General Surgery, Mayo Clinic, Rochester, M N 55905
26
tus. With the advent of endoscopic retrograde cholangiography, the radiographic diagnosis of PSC was made more readily and an association between PSC and chronic ulcerative colitis became more apparent. Schrumpf et al' reported cholangiographic evidence of PSC in 19 of 336 patients (6%) with chronic ulcerative colitis. Conversely, approximately 70 to 80% of patients with PSC have chronic ulcerative colitis."-x Patients with chronic ulcerative colitis clearly have a predisposition to develop cholangiocarcinoma. Parker and Kendally reported a single patient with cholangiocarcinoma in an autopsy study of 39 livers from patients with chronic ulcerative colitis in 1954. Subsequently, many case report^""^ and several series"-18 have described cholangiocarcinoma in patients with chronic ulcerative colitis. Roberts-Thomson et al" observed four cases of cholangiocarcinoma in 292 chronic ulcerative colitis patients seen over a 14-year period, for a frequency of 1.4%. They estimated that the probability of both diseases occurring together by chance alone was extremely small (p
