Asymptomatic Type I Mirizziʼs Syndrome Secondary to Busulfan Therapy

Abstract

Purpose: Background: Complications from asymptomatic gallstone disease are rare. In 1948, Mirizzi described a syndrome of hepatic duct obstruction in the setting of cholelithiasis and cholecystitis, presenting with jaundice, abdominal pain, and recurrent cholangitis. Risk factors for this condition, however, have not been well-elucidated. We describe the first-reported case of possible busulfan-induced Mirizzi syndrome in an asymptomatic patient. Case Report: A 63 year old female with a history of transfusion-dependent myelodysplastic syndrome and acute myelogic leukemia presented to her hematologist's office for a routine visit where she was noted to be icteric. The patient had received one dose of busulfan at 100 mg/m2 for consolidation therapy 7 weeks prior to admission following induction with Ara-C, idarubicin, and etoposide. She did not receive cyclophosphamide. She denied any abdominal pain or fever, however she had developed light-colored stools and dark urine for the past 4 days. Physical exam was notable for hepatomegaly and scleral icterus. Laboratories revealed a total bilirubin of 3.7, direct bilirubin 3.7, alkaline phosphatase 487, AST 234, ALT 430, and a white count of 3.5. An abdominal ultrasound and CT scan showed multiple gallstones, a thickened gallbladder wall, and biliary ductal dilation. Endoscopic retrograde cholangiography was performed which demonstrated a smooth 1.8 cm long stricture in the proximal CHD with upstream dilation of the right, left, and intrahepatic ducts. The cystic duct was not opacified. A plastic biliary stent was inserted, with good drainage achieved. She subsequently underwent open cholecystectomy where a markedly enlarged gallbladder was found, packed with multiple pigmented stones of nearly identical shape and size with the exception of a 2 cm stone obstructing the gallbladder neck and cystic duct. Histopathology revealed an acutely and chronically inflamed gallbladder with fibrous tissue. Conclusion: Busulfan may be a rare cause of acute cholecystitis during induction chemotherapy. In one case series, 5 out of 35 patients had acute cholecystitis within 18 days of treatment after receiving cyclophosphamide and busulfan, and all presented with abdominal pain and fever. Our patient was unique given the absence of symptoms, and the concomitant presentation of Mirrizi syndrome. It is unclear if the stones are due to crystallized drug or due to recurrent hemolysis. Acute cholecystitis and its complications should be considered in patients undergoing induction chemotherapy with busulfan.