Yang Qin, Zhou Yong, Li Fu-Yu, Mao Hui, Shrestha Anuj, Ma Wen-Jie, Cheng Nan-Sheng, Zhang Wei
Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.
Hepatobiliary Pancreat Dis Int. 2015 Oct;14(5):509-15. doi: 10.1016/s1499-3872(15)60395-2.
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.
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.
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.
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.
目前尚无有效的药物可预防胆管镜取石术后结石复发或治疗作为肝内胆管结石病理基础的增生性胆管炎（PC）。本研究旨在探讨表皮生长因子受体（EGFR）抑制剂吉非替尼是否能抑制PC中的胆管增生和结石形成。
对94例肝内胆管结石患者进行胆管镜取石术后，在病变胆管腔内留置导管。随后，94例患者中的49例通过导管每周两次接受250mg吉非替尼溶液治疗，并在6周和12周时接受胆管镜活检。其余45例未接受吉非替尼治疗的肝内胆管结石患者作为对照。
与对照组相比，接受吉非替尼治疗12周的患者中EGFR、PCNA和I型前胶原的表达显著降低。与对照组相比，吉非替尼组患者的胆管上皮、黏膜下腺和胶原纤维增生程度低得多。吉非替尼治疗显著降低了黏蛋白3的表达和β-葡萄糖醛酸酶的活性。
术后吉非替尼治疗可显著抑制PC介导的增生和结石形成，这可能为预防肝内胆管结石患者的胆管再狭窄和结石复发提供一种新策略。
