Hepatolithiasis and intrahepatic cholangiocarcinoma: A review

Abstract

Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma (CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA (HL-CCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliary-enteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.

Keywords: Cholangiocarcinoma; Hepatolithiasis; Intrahepatic; Management.

Figure 1

Sixty-seven years old, female was admitted for cholangitis and treated with hepatic resection. She was followed and underwent second resection 1 year later. A: Abdominal computed tomography demonstrated that B2 IHD dilatation with stones and 2 cm sized low density lesion in liver S7; B: Liver, left, lateral, segmentectomy was done; C: BilIN1 and two were shown on dilated duct with glandular proliferation.

Figure 2

Sixty-seven years old, female was admitted for cholangitis and treated with hepatic resection. She was followed and underwent second resection 1 year later. A: Follow-up abdominal computed tomography. Exophytic hypodense mass in S7 of the liver was more enlarged with peripheral enhancement; B: Liver, S7, segmentectomy was done; C and D: Hematoxylin and eosin (HE) statin (C: × 12.5; D: × 200). Intraductal papillary neoplasm with an associated invasive carcinoma. 6 cm × 3 cm × 3 cm sized intraductal papillary neoplasm including 0.6 cm × 0.5 cm sized invasive tumor.

Figure 3

Molecular mechanism of hepatolithiasis-associated cholangiocarcinoma. HL-CCA: hepatolithiasis-associated cholangiocarcinoma; NF-κB: Nuclear factor kappa-B; EGFR: Epidermal growth factor receptor; PGE₂: Prostaglandin E2; COX-2: Cyclooxygenase-2; IPNB: Intraductal papillary neoplasm of the bile duct; BilIN: Biliary intraepithelial neoplasia.

Figure 4

Forty-six years old, female was admitted for cholangitis. A: Abdominal CT demonstrated that multiple calcified stones are present in the lateral segment of the left lobe; B: Liver, left lobectomy was performed, and there was no cancerous lesion; C: Abdominal computed tomography taken 14 mo after resection demonstrated development of cholangiocarcinoma in the caudate lobe of the liver.