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School of Medicine
Immune Mediated Liver Diseases
A Randomized Study of Intraductal Mitomycin C Therapy for Primary Sclerosing Cholangitis
Marcia Canto, M.D., M.P.H.
Po-hung Chen, M.D.
Anthony Kalloo, M.D.
Mouen Khashab, M.D.
Anne Marie Lennon, M.D.
Patrick Okolo, M.D.
Eun Ji Shin, M.D.
Vikesh Singh, M.D., M.Sc.
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation, fibrosis and multifocal biliary strictures. Currently, there is no proven therapy to alter PSC progression except liver transplant.
Endoscopic retrograde cholangiography (ERC) is the standard of reference for diagnosis of PSC. Advantages of ERC include increased visual sensitivity to evaluate peripheral intrahepatic duct abnormalities and interventional capabilities such as mechanical dilation of obstructing strictures with or without stent placement.
While ERC acutely manages symptoms, the technique has a limited role, if any, in slowing the progression toward cholestatic liver failure. Dominant extrahepatic strictures, managed mechanically by balloon dilation and stent deployment, frequently recur, necessitating repeat ERC. Moreover, the small caliber of intrahepatic ducts is not amenable to mechanical manipulation by our current technologies.
Adjuvant mitomycin C (MMC) has been used to prevent scar formation following varied surgical interventions. MMC’s mechanism of action is to slow fibroblast cell division and proliferation. The fibroblast cells are the main source of the synthesis and deposition of scar tissue. Interruption of this process with MMC would therefore delay and perhaps prevent recurrent scar tissue formation in the bile ducts that lead to obstruction. The biliary strictures found in PSC present similar pathophysiology to that successfully treated with adjuvant mitomycin elsewhere.
The primary aim of the study is to determine the efficacy of mitomycin C intrabiliary bolus on survival and the progression of PSC. Other aims of the study are to determine the durable effect of mitomycin on interval duration between procedures, the total number of procedures needed over a two-year period for the routine management of PSC and the change of serum biochemical markers.
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