title: Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis.
abstract: 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 beta-glucuronidase activity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, China. lfy_74@vip.163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Anuj
authors.initials: A
authors.lastname: Shrestha
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Ma
authors.forename: Nan-Sheng
authors.initials: NS
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000473:pathology*; D002761:Cholangitis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics; D016145:Endoscopy, Digestive System; D004848:Epithelium / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D015870:Gene Expression; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy; D019394:Ki-67 Antigen / Q000032:analysis; D020347:Lithiasis / Q000209:etiology*; D008107:Liver Diseases / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D055263:Mucin-3 / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D024042:Collagen Type I; D019394:Ki-67 Antigen; D055263:Mucin-3; D018809:Proliferating Cell Nuclear Antigen; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D005966:Glucuronidase; D000077156:Gefitinib