1、答辩委员会主席：论文答辩日期： 二一四年五月二十日院校地址：北京市复兴路28号 邮政编码：100853军医进修学院研究生学位论文原创性声明 秉承我院“敬业、勤奋、求实、创新”到学风，本人声明：所呈交的论文是我本人在导师指导下进行的研究工作及取得的研究成果。据我所知，除了文中特别加以标注和致谢的地方外，论文中不包含任何其他个人或具体已经发表或撰写过的研究成果，也不含为获得我院或其他教育机构的学位及证书而使用过的材料，对本文的研究作出贡献的个人或集体，均已在文中做了明确的说明并表示谢意。 申请学位论文与资料若有不实之处，本人承担一切相关责任。 论文作者签名： 日期：指导教师签名：研究生学位论文版权
2、使用授权书本人保证毕业离院后，发表论文或使用论文工作成果时署名单位为军医进修学院或解放军总医院。学院有权保留并向国家有关部门或机构送交论文原件、复印件和电子版本，可以采用影印、缩印、扫描或其它手段保存论文以供被查阅和借阅。学院可以公布学位论文的全部或部分内容（保密内容除外）。中文摘要（1）英文摘要（3）英文缩略词汇表（8）论文正文（8）前言（6） 第一部分 I125放射性粒子植入计划的三维模型设计及植入方法的研究 材料与方法（8） 结果（8） 讨论（15） 第二部分 术中I125放射性粒子植入治疗晚期胰腺癌的疗效分析结论（6）参考文献（30）文献综述（32）攻读学位期间发表文章情况（40）致
3、谢（41）中 文 摘 要本课题拟通过对无法切除的晚期胰腺癌患者进行术前三维数字模型的建立，来制定放射性粒子I125的肿瘤内植入计划并对粒子植入的方法进行研究，同时进行双旁路手术（胆肠、胃肠吻合）以解决患者目前存在的症状如疼痛、黄疸、胃排空障碍或术后可能出现的上述问题。胰腺癌预后很差，外科切除手术是唯一有可能治愈胰腺癌的治疗方式，但只有5%22%的患者可以接受根治性切除手术，无法行根治性切除的晚期胰腺癌病人只能接受各种各样的姑息性治疗。肿瘤内放射性粒子I125植入术是其中一种有效的治疗方法，我们通过综合分析文献及预实验后发现改进放射性粒子植入的方法，也就是说最大程度地按照肿瘤的立体形状，将粒子在
4、肿瘤空间内均匀地植入能提高患者的生存时间，同等条件下植入粒子越彻底、越精准、越能延长患者的生存时间。并且通过预实验我们发现部分患者能获得与根治性切除手术相同的生存时间，故本项目是一项以提高患者生存时间为主要预期目标，改善晚期肿瘤患者症状、生活质量为次要预期目标的临床研究。目的：本课题分为两个部分，第一部分从植入计划的三维模型设计及植入方法着手，运用三维软件系统对粒子植入进行术前三维模型的设计，预期达到手术中放射性粒子能完全覆盖肿瘤，没有盲点、冷点，同时又不伤及周围组织及血管的目的。第二部分按照我们设计的粒子植入方法，对晚期胰腺癌患者进行粒子植入手术，通过对患者生存期、生活质量的病例总结，分析可
5、行性与安全性，评估其临床价值。方法：根据相关纳入标准，运用EDDA三维重建软件系统，对在解放军总医院肝胆外科2009年1月至2013年12月收治的47例晚期胰腺癌患者，进行胰腺肿瘤与周围血管、组织的三维重建，并根据肿瘤立体空间位置的测算，计算粒子需要植入的数量，并模拟粒子植入的过程。手术中严格按照术前设计方案进行，对可能存在的盲点进行粒子的“补种”。随后就其影像学资料、治疗结果、随访情况等方面作一综合性分析及研究。并将我院同期行姑息性手术治疗的78例晚期胰腺癌患者作为对照组，将两组患者之间的临床资料进行对比分析。结果：1、研究期间，我科共对47例晚期胰腺癌患者实施粒子植入术，其中男性29例，女
6、性18例。年龄36-87岁，平均年龄57.612.0岁。2、运用EDDA三维重建软件系统对粒子植入进行术前三维模型的设计，进行胰腺肿瘤与周围血管、组织的三维重建，进行肿瘤立体空间位置的测算，计算粒子需要植入的数量，并模拟粒子植入的过程。3、所有患者均行术中I125植入术，粒子植入数为16粒-116粒，平均53.119.8粒，其中5例患者同时行胃肠吻合术、10例患者同时行胆肠吻合术、13例患者同时行胆肠吻合加胃肠吻合术、19例患者仅行粒子植入术。4、粒子组患者术后发生胃瘫11例、胆瘘1例、菌血症1例，9例患者出现胰瘘，分级为A级8例、B级1例，1例患者术后第12天发生腹腔出血，经保守治疗后好转，
7、并发症Clavien分级I级10例，II级13例，无围手术期死亡患者。粒子组术后并发症的总发生数要明显高于对照组患者，因此该组术后住院时间也要长于对照组患者。但粒子植入术并没有增加严重并发症（Clavien分级II级）的发生率、无围手术期死亡患者。粒子植入组患者胰瘘和胃瘫的发生率要高于对照组患者。25例首发症状以腹痛前来就诊患者，术后出院时仍有腹痛患者8例，分为轻度5例，重度3例，腹痛缓解率为88%（22/25）。本组资料中术后共11例患者出现胃瘫综合征，经统计分析考虑，术后胃瘫的发生与是否行胃肠吻合，以及行胃肠吻合的同时是否行粒子植入术密切相关。5、粒子组47例患者中42例得到随访，随访率为
8、89.4%，获得随访患者的1月、半年、1年、2年的生存率分别为97.6%、62.4%、25.8%、14.3%，平均生存时间为13.01.2个月，明显优于对照组患者。结论：1、对于不能行根治性切除的晚期胰腺癌患者，放射性粒子植入术是一种安全有效的治疗手段。2、放射性粒子植入术并不会增加患者的死亡风险，是安全可行的，其能明显延长晚期胰腺癌患者的生存时间，提高患者的生活质量。3、采用术前三维模拟粒子植入的方法，即最大程度地按照肿瘤的立体形状将粒子在肿瘤空间内均匀地植入，提高粒子植入的精确性，最大限度地延长患者的生存时间，甚至部分患者能获得与根治性切除手术相同的效果。关键词：晚期胰腺癌；I125粒子；
9、外科治疗；生存时间；生活质量AbstractIn this study, we through the establishment of unresectable advanced pancreatic cancer patients with preoperative three-dimensional digital model, research to develop radioactive seeds implantation of I125 planning and implantation method. At the same time through double bypass
10、 operation （biliary obstruction, gastrointestinal anastomosis） to solve patients present symptoms, such as pain, jaundice, gastric emptying and so on. Pancreatic cancer is very poor, surgical operation is the only cure method for the treatment of pancreatic cancer, but only 5% to 22% of patients can
11、 accepted radical resection operation, the other patients can only accept expectant treatment. Radioactive I125 seeds implantation is an effective method in the treatment of the improved pancreatic cancer. We found that radioactive seeds implantation through a comprehensive literature analysis and p
12、re-experiment can improve the survival time of the patients. That is to say the maximum implantation according to the three-dimensional shape of the tumor, in this case, we can prolong the survival time of patients. And through pre-experiment we found that some patients can obtain the same survival
13、time with radical resection operation. So this article targets are to improve the survival time of patients and improve the quality of life of patients.Objective: The purpose of this paper is divided into two parts, the first part starts from the 3D model design and implantation method. The design o
14、f 3D software system for the preoperative 3D model of particle implantation, is expected to fully cover the tumor and no blind spot, while not harming the surrounding tissues and the blood vessels. The second part according to the seeds implantation method. According to the quality of life, survival
15、 period of patients, the feasibility analysis of safety to evaluate its clinical value.Methods: According to the inclusion criteria, using EDDA 3D reconstruction software system, 47 patients with advanced pancreatic cancer in PLA General Hospital from 2009 January to 2013 December in our hospital de
16、partment of hepatobiliary surgery. We finished 3D reconstruction of pancreatic tumor and surrounding blood vessels, tissue, and according to the calculation of three-dimensional space position of the tumor, calculate the number of seeds needed implantation, and simulation of seed implantation. Opera
17、tion in strict accordance with the preoperative design, particle on the possible existence of blind spot. Analysis and research of imaging data, treatment, follow-up results etc. And in our hospital underwent palliative operation treatment of 78 patients with advanced pancreatic cancer as the contro
18、l group, the clinical data between the two groups of patients were compared and analyzed.Result.1. During the study period, a total of 47 cases of advanced pancreatic cancer patients with seeds implantation, including 29 cases of male, female 18 cases. Ages were 36-87 years old, and the average age
19、was 57.612 years old.2. The design of EDDA 3D reconstruction software system for preoperative 3D model of seed implantation, 3D reconstruction of pancreatic tumor and surrounding blood vessels, tissue, calculate tumor stereo space position, calculate the number of seeds needed implantation, and simu
20、late the process of particle implantation.3. All patients underwent intraoperative I125 implantation, implantation for 16 -116 seeds, with an average of 53.119.8 seeds, 5 of them underwent gastrointestinal anastomosis, 10 cases underwent biliary-enteric anastomosis, 13 cases underwent biliary-enteri
21、c anastomosis and gastrointestinal anastomosis, 19 patients only received seeds implantation.4. Seed group of patients with postoperative gastroparesis in 11 cases, 1 case of biliary fistula, 1 case of bacteremia, 9 patients had pancreatic fistula, 8 cases of Grade A, 1 case of Grade B, 1 patient oc
22、curred intraperitoneal hemorrhage at twelfth days after operation and cured by conservative therapy. Complications contains 10 cases of Clavien grade I, II grade of 13 cases, no peri-operation period death patients. Postoperative complications of seed group occurred significantly higher than the tot
23、al number of patients in the control group, and the postoperative hospitalization time was longer than control group patients. But seed implantation did not increase severe complications （Clavien grade II） incidence, no peri-operation period death patients. Seed implantation in patients of pancreati
24、c fistula and gastroparesis incidence was higher than that of the control group of patients. The first symptom of 25 cases with abdominal pain to patients, postoperative abdominal pain patients was 8 cases, divided into 5 mild cases, 3 severe cases, the remission rate of abdominal pain was 88%（22/25
25、）. The data of 11 patients with postoperative gastroparesis, through statistical analysis and consideration, the occurrence of postoperative gastroparesis is closely related to whether gastrointestinal anastomosis, and at the same time for seed implantation.5. S eed group of 47 patients, 42 cases we
26、re followed up, the follow-up rate was 89.4%. The one month, half of year, one year, and two year survival rates of particle group were 97.6%, 62.4%, 25.8% and 14.3%, the average survival time was 13.01.2 months. The survival rates and time were significantly higher than control group（P0.05）.Conclus
27、ion:1. For cant radical resection patients with advanced pancreatic cancer, radioactive seeds implantation is a safe and effective treatment method.2. Radioactive seeds implantation did not increase the risk of death in patients, is safe and feasible, which can obviously prolong the survival time of
28、 patients with advanced pancreatic cancer, improve the quality of life of patients.3. By using the method of preoperative three-dimensional simulation of particle implantation, namely the maximum according to the three-dimensional shape of tumor implantation, improve the accuracy of particle implant
29、ation, prolong the survival time of patients, and even some patients can obtain treatment as the radical operation.Keywords: Advanced pancreatic cancer; I125 seed; Surgical treatment; Survival time; Quality of life英文缩略语词表英文缩写英文全称中文全称TPStheraphy planning system计算机立体定位计划系统MSvmilliSievert毫西弗TACEtransarterial chemoembolization经导管动脉化疗栓塞RFAradiofrequency ablation射频消融术GyGray戈瑞CRComplete Response完全缓解PRPartial Response部分缓解I125Iodine-1
