BACKGROUND: There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis(PC), which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor(EGFR) inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.METHODS: After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.RESULTS: The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and β-glucuronidase activity.CONCLUSION: Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.
BACKGROUND: The high recurrence rate of hepatolithiasis and the high operative risk of right posterior, caudate or multiple lobe hepatectomy are the unsettled problems in hepatobiliary surgery. The present study was to investigate the efficacy of chemical hepatectomy performed via applying sequential embolization of the branches of the bile duct and portal vein to the targeted hepatic lobe. METHODS: The bile duct and portal vein branches of the median hepatic lobe of rats were treated with: 1) bile duct embolization followed by portal vein ligation(BDE+PVL) and 2) portal vein ligation followed by bile duct embolization(PVL+BDE). The efficacy of chemical hepatectomy in BDE+PVL and PVL+BDE groups was compared with that of sole BDE by histology and Western blotting analysis of collagen I expression. RESULTS: After six weeks of the chemical hepatectomy, rats in the BDE group showed hepatocyte damages, fibrosis and "selfcut" only in the periphery of the embolized lobe. In contrast, rats in the PVL+BDE and BDE+PVL groups exhibited complete necrosis of hepatocytes and replacement with proliferative ductules and collagen fibers, leading to complete fibrosis and "self-cut" phenomenon in the whole targeted lobe. Collagen I expression in the PVL+BDE group was slightly higher than that in the BDE+PVL group; however, no statistically significant difference was noted. CONCLUSION: The sequential embolization of the bile duct and portal vein branches to the targeted hepatic lobe may bea feasible and effective approach to acheive the ideal effect of chemical hepatectomy in a short period of time.
