超声内镜引导基因重组人溶瘤腺病毒植入治疗晚期胰腺癌初步研究

EUS-guided oncolytic adenovirus implantation in patients of non-operative pancreatic cancer

目的探讨EUS引导基因重组人5型腺病毒H101植入联合吉西他滨治疗晚期胰腺癌的安全性及其临床价值。方法自2007年5月-12月，共6例晚期胰腺癌患者于EUS引导下将H101分3点注入瘤体内，第2、9、16天行吉西他滨全身化疗，1个月为1个周期，共2个周期。采用计算机三维重建及灌注成像技术观察肿瘤体积改变及瘤体内部血流灌注情况，记录临床指标的改善、不良反应及并发症等。结果6例患者均按预定计划完成治疗，其中5例肿瘤体积较治疗前不同程度缩小（18．21％～38．65％），但差异无统计学意义（P=0．078）。1例肝脏转移灶明显缩小。灌注成像显示治疗后2周平均通过时间较治疗前明显延长（P=0．049），血流量、血容量及表面通透性呈有利改变。2例卡诺夫斯基量表评分提高，3例疼痛评分明显下降。3例患者已死亡（生存期分别为2．5、2．5、3个月），3例仍存活患者生存期分别为3、5、10个月。不良反应主要为发热和流感样症状，1例患者发生轻症胰腺炎。结论结果初步提示EUS引导基因重组人5型腺病毒植入治疗晚期胰腺癌临床安全、可行，与吉西他滨联合具有潜在缩小肿瘤体积、破坏肿瘤血供及改善患者生存质量的作用。

Objective To observe the safety and efficacy of oncolytic adenovirus （H101） implantation under EUS guidance combined with gemcitabine in patients of non-operative pancreatic cancer. Methods From May 2007 to December 2007, 6 patients with non-operative pancreatic cancer were enrolled in the study. H101 were implanted into 3 sites of the tumor under EUS guidance. Gemcitabine was given systemicly on d2, d9 and dl6 after implantation, and repeated 1 month later. Tumor size and perfusion were assessed by computed reconstruction and perfusion imaging. Changes of clinical indices, adverse effects and complications were also recorded. Results All patients completed the two periods of treatment as planned. Tumor size decreased in 5 cases（ 18. 21% -38.65% ）, but without statistical difference （P =0. 078）. The area of liver metastasis was found decreased in 1 case. Perfusion imaging showed significant increase of mean transit time （ P = 0. 049 ） and improvement in blood flow, blood volume and permeability surface at 2 weeks after the treatment. KPS increased in 2 patients and pain score decreased in 3 patients. Three patients died 2. 5, 2. 5 and 3 months respectively after the procedure, while 3 other patients are still alive with the survival time of 3, 5 and l0 months. Major adverse effects associated with H101 implantation were fever and flu-like symptoms. Mild acute pancreatitis occurred in 1 case. Conclusion EUS guided oncolytic adenovirus implantation in advanced pancreatic cancer is feasible and safe. With the combination of gemcitabine, it is capable of shrinking the tumor size, destroying the angiogenesis of the tumor and improving the patients living quality.