125I放射性粒子气管支架对犬气管及周围组织放射性损伤的实验研究

【摘要】 目的 探讨于实验犬气管内放置125I放射性粒子气管支架后气管及周围组织（食管、主动脉弓、肺组织）的放射性损伤情况。方法 选取健康成年杂种犬24只,随机分为实验组和对照组,每组12只,在X线透视下经口行气管支架置入术,实验组支架装有2排共8颗0.7 mCi（25.9 MBq）125I放射性粒子,对照组为相同排列方式无放射性的空粒子。术后2、3和4个月分别抽取各组犬4只,复查影像学与实验室检查,处死后取支架留置段气管及周围组织（食管、主动脉弓、肺组织）行病理学检查。结果 观察过程中无实验动物死亡,实验犬呼吸、进食和发声均正常,SPECT/CT随防观察到实验组有1只犬发生1颗粒子脱落。两组实验犬气管组织随观察时间延长损伤程度加重,4个月损伤严重程度高于3个月组,3个月损伤严重程度高于2个月组,差异均有统计学意义（P＜0.05）。但实验组和对照组各亚组间对比,损伤程度相似,差异无统计学意义（P＞0.05）。所有实验犬支架留置段在各观察期内食管、主动脉弓及肺组织均无明显损伤,两间无明显差异,差异无统计学意义（P＞0.05）。结论 125I放射性粒子支架在实验犬气管中置入是可行的、安全的。     

食管内照射支架的研制及动物实验研究

目的通过在食管支架上预置125I粒子探索食管内照射支架研制的可行性;通过动物实验探讨内照射支架的安全性。方法(1)食管内照射支架的研制:用模具以塑料为原料制成刚好装填1颗125I粒子的“弹匣”,并将其缝制在食管支架外周,即制成食管内照射支架。(2)动物实验:选择实验用兔36只,分成4组。根据不同的照射剂量将实验组分为3组(单个粒子剂量×2颗粒子):A组22.2 MBq、B组44.4 MBq、C组66.6 MBq;D组为对照组,植入无放射粒子的支架。于术后2、4、8周分别取各实验组和对照组兔3只,处死前行食管造影、CT等检查,观察支架、粒子移位情况;支架标本分别行肉眼、光学显微镜(简称光镜)、电子显微镜(简称电镜)下观察;观察指标包括食管及其周围肺、支气管、大血管的损伤及程度。结果(1)食管内照射支架的研制:125I粒子能被牢固地固定在支架外周,动物实验证明:放射粒子装填方便,支架释放简单,支架释放过程及术后随访未发现125I粒子丢失。(2)动物实验:8周时实验组粒子附近食管壁增厚最明显[A组(4.2±0.3)mm,B组(4.3±0.3)mm,C组(4.5±0.3)mm],与对照组[(3.1±0.1)mm]比较差异有统计学意义(P<0.05),各实验组之间差异无统计学意义(P>0.05)。食管内径在上述观察期内实验组、对照组都表现为随时间的延长管腔逐渐变窄,8周时各实验组管腔直径[A组(5.7±0.2)mm,B组(5.6±0.3)mm,C组(5.6±0.3)mm]与对照组[(5.6±0.2)mm]比较差异无统计学意义(P>0.05)。8周内实验组支架周围的肺、气管、胸主动脉壁与对照组肉眼、光镜所见基本一致。但电镜下上述器官组织超微结构有轻微损伤。结论捆绑式食管内照射支架的设计、制作是可行的;动物实验表明:临床常用活度的125I放射粒子对食管周围肺、气管及大血管等正常器官组织造成的损伤是轻微的;125I放射粒子对支架引起的增生的食管黏膜无明显的抑制和刺激作用;125I放射粒子长时间植入体内可能对食管平滑肌有刺激增生作用。     

125I放射粒子在肿瘤介入治疗中的应用

目的 探索采用介入微刨技术进行放射粒子病灶内植入的可行性、安全性及疗效;比较不同影像设备在粒子植入术中的作用及优缺点。方法 入选30例患者,其中15例为晚期肿瘤转移患者,15例为失去手术机会的食管癌患者。粒子植入方法：在B超或CT定位下行经皮穿刺病灶内粒子植入术;在DSA监视下将捆绑有放射粒子的食管支架植入到食管病变部位。结果 在B超、CT及DSA监视下,除因操作原因造成食管内照射支架上丢失一颗放射粒子外,所有放射粒子均准确植入到位。术后随访,患者临床症状均有明显改善;未发现局部皮肤坏死、出血、感染、放射性肺炎、食管穿孔等与粒子照射相关的并发症;手术前后连续血象、免疫指标复查未发现显著性变化。ECT复查：放射源未发现泄漏。病灶复查：15例食管癌患者1个月后胸部CT复查示13例病变厚度和体积较术前有所缩小,2例病变增大,3例随访近13个月,CT复查病变厚度较术前明显变薄;5例直接置入无膜内照射支架患者中3例术后3个月胃镜复查并活检提示支架捆绑粒子部位肿瘤明显退缩,未发现肿瘤细胞生长。15例经皮穿刺植入粒子的患者在术后2个月病变明显缩小。结论 采用介入微创技术进行放射粒子病灶内植入是可行的、安全的,疗效是明确的。     

镍钛合金避孕栓对新西兰兔输卵管组织结构的影响

 目的 研究新西兰雌兔输卵管放置镍钛合金避孕栓对输卵管组织结构的影响.方法 18只新西兰雌兔随机分成实验组、自身对照组和正常对照组,实验组每只双侧各放置一个镍钛合金避孕栓,自身对照组每只仅右侧放置一只镍钛合金避孕栓,对侧不放置.正常对照组双侧均不放置镍钛合金避孕栓.分别于避孕栓植入后的第3个月、6个月和12个月检查雌兔的受孕和分娩状况,随后处死雌兔,取出避孕栓,肉眼并结合光镜检查输卵管组织结构的变化.结果 避孕栓置入3个月后,实验组的双侧输卵管及自身对照组的右侧输卵管黏膜皱襞参差不齐,黏膜及黏膜下层充血,水肿,黏膜皱襞间质有急性炎症细胞浸润,并有上皮层脱落现象.避孕栓放置6个月和12个月后,实验组的双侧和自身对照组右侧输卵管粘膜有少许炎性细胞浸润及纤维细胞的轻度增生.结论 镍钛合金避孕栓对雌兔输卵管组织和结构无明显的影响.     

经胆管192Ir内照射对犬胆管周围肝组织放射损伤的实验研究

目的:通过研究经胆管192Ir内照射(192Ir-internalirradiation,192 Ir-IIR)对胆管周围肝组织放射损伤,探讨经胆管192 Ir-IIR的有效治疗范围。方法:实验动物为雄性健康杂种犬4只,体重25~30kg。经手术将施源管植入胆管,根据预先设定的剂量及照射点进行胆管内近距离照射。放射源采用192Ir。内照射10天后处死动物,距离胆管壁由近及远按设计距离分别取1mm×1mm×1mm大小肝组织,常规制备光镜切片,作TUNEL染色;同时常规制备电镜切片。光镜下观察周围肝组织的放射损伤同时计数凋亡肝细胞。电镜下观察肝组织超微结构损伤变化并计数凋亡肝细胞。结果:在胆管最大耐受剂量50Gy时,距胆管15mm内肝细胞核出现不可逆性改变。结论:距放射源15mm可以作为有效治疗范围。     

食管内照射支架的研制及临床应用的初步结果

目的探索食管内照射支架研制、临床使用的可行性、安全性及初步疗效。方法选择合适的覆膜或裸食管支架，于支架外周按一定的规律固定上特制的可容纳放射粒子的鞘，根据患者病变的范围通过治疗计划系统(treatment plan system，TPS)计算出放射粒子的剂量，将放射粒子装进上述鞘内即制成食管内照射支架。临床选择15例食管癌患者，临床分级为Ⅱ～Ⅳ级，将放疗支架植入到患者病变食管内并进行临床随访。结果15例患者内照射支架均释放到位，释放过程顺利，释放过程中未出现放射粒子脱落现象；全身γ射线显像(ECT)复查未发现非靶器官显像；患者全身一般状况明显好转，血象和免疫指标亦未见明显变化，未出现如食管穿孔、出血等并发症；13例术后1个月CT复查提示病灶的厚度较术前变簿，2例变大，3例随访近8个月，CT复查病变厚度较术前明显变薄，胃镜检查并活检提示支架捆绑粒子部位肿瘤明显缩小，活检未发现肿瘤细胞生长。结论食管内照射支架临床使用是安全、可行、有效的，其临床长期疗效需进一步随访观察及对照研究。     

经胆管192Ir内照射对胆管、肝脏放射损伤的实验研究

目的 探讨经胆管192Ir内照射的安全性、可行性以及有效治疗范围,为肝门部胆管癌经胆管192Ir内照射提供理论依据.方法 取雄性健康杂种犬16只,据照射剂量随机分成4组,每组4只.内照射前从犬肝边缘切取1 cm3大小肝组织作对照研究.术中将近距离治疗施源器经胆囊送入胆囊管与肝总管汇合处并用金属夹固定,根据预先设定的剂量进行胆管内照射.10 d后处死动物,取被照射胆管中央部分长约5 mm胆管,及距离胆管壁由近及远按设计距离分别取1 mm3大小肝组织,制备光镜切片,作HE染色;同时用2.5%戊二醛固定后常规制备电镜切片.光镜下观察胆管及周围肝组织的放射损伤并对损伤程度评分.电镜下观察肝组织超微结构损伤变化并计数凋亡肝细胞.结果 经胆管192Ir内照射30 Gy时,胆管损伤达部分肌层;50 Gy时,胆管仅存外膜;60 Gy时,胆管出现全层坏死.胆管周围肝组织放射损伤随剂量增加而加重.在胆管最大安全耐受剂量50 Gy时,距胆管0～15 mm处肝细胞核出现不可逆性改变.结论 正常胆管对192Ir内照射有良好的耐受性.在胆管最大安全耐受剂量50 Gy时,经胆管192Ir内照射有效的治疗范围可达15 mm.     

拖入式内支架胆肠吻合新方法的实验研究

目的 研究拖入式内支架吻合技术对小口径胆肠吻合的影响。方法18只小型猪被随机分成两组：一组常规行间断缝合胆管空肠吻合术（n＝9,对照组）,另一组行拖入式内支架胆管空肠吻合术（n＝9,实验组）。结果实验组吻合时间明显短于对照组（13.1±1.8min vs 25.8±2.0min,P＜0.05）;术后6个月对照组胆肠吻合口内径明显小于实验组（2.9±0.2mm vs 3.8±0.3mm,P＜0.05）;所有内支架管都在56d内自行脱落排出;对照组2例发生吻合口狭窄,其余16例（对照组7例,实验组9例）肝功能、肝组织形态均正常。结论新的拖入式内支架吻合技术在小口径胆肠吻合中安全易行。     

125I粒子食管内照射支架治疗中晚期食管癌（附15例报告）

目的:探讨携带125I粒子食管内照射支架治疗中、晚期食管癌的可行性、安全性及初步疗效。方法:术前、术后行血常规、出凝血时间及肝肾功能监测,根据患者病变的大小估算出125I粒子数,选择合适的覆膜食管支架,于支架外周按一定的规律固定上125I放射粒子,制成食管内照射支架。选择15例临床分级为Ⅲ~Ⅳ期食管癌患者,将食管内照射支架植入到患者食管内并进行临床随访。结果:15例患者内照射支架均释放到位,释放过程顺利,释放过程中未出现放射粒子脱落现象。支架置入后患者一般状况明显好转,血液分析指标亦未见明显变化,未出现如食管穿孔、出血等并发症,术后3个月CT复查12例病灶较术前明显缩小、2例稍缩小、1例无明显变化;15例随访6个月,均未见出现食管再狭窄或食管瘘。结论:食管内照射支架临床使用是安全、可行、有效的;短期临床观察,治疗中、晚期食管癌携带125I粒子食管内照射支架优于传统支架。     

Effects of a holmium-166 incorporated covered stent placement in normal canine common bile ducts

PURPOSE: A specially designed self-expandable covered metallic stent incorporated with beta-emitting radioisotope, Holmium-166 (Ho-166), was developed for delivering intraluminal brachytherapy as well as for internal bile drainage in malignant biliary stricture. The purpose of the study was to demonstrate the safety and tissue response of the radioactive metallic stent on the normal canine common bile duct (CBD) prior to the clinical application. MATERIALS AND METHODS: Nitinol self-expandable stents (diameter; 4 mm, length; 20 mm) were covered with polyurethane membrane (50 microm thick) containing 21 to 135 muCi of Ho-166 (mean, 77.9 microCi). To prevent migration of stent, the membrane covered only the middle 1 cm of the stent and the ends of the stent were left uncovered. The stents were placed in the CBD of 20 healthy beagle dogs. For control, non-radioactive covered stents were placed in another three dogs. The dogs were killed 3 to 6 months after stent insertion and histopathologic examination of CBD was performed. RESULTS: There was no stent migration in all cases. Varying degrees of papillary mucosal hyperplasia leading to significant narrowing of the lumen was observed within the lumen of the bare portion and under the mucosal surface of the non-radioactive covered stents. However, fibrosis was noted in Ho-166 coated area, instead of mucosal hyperplasia. Severity of fibrosis was correlated with estimated radiation dose. Despite high dose, there was no perforation of CBD wall. The membrane of Ho-166 coat was disrupted in some cases of 6 months follow-up. CONCLUSIONS: Holmium-166 incorporated covered stents demonstrated fibrosis of CBD wall and inhibition of ingrowth of mucosal hyperplasia without serious complication such as perforation, while control group showed severe mucosal hyperplasia.     

Palliation of malignant bile duct obstruction with metallic biliary endoprostheses: technique, results, and complications.

Expandable metallic stents were placed in 34 patients with pathologically proved malignant bile duct obstruction to determine ease of insertion, benefits of a one-stage insertion, and cost-effectiveness relative to conventional plastic stents. Thirty-eight strictures, ranging in length from 1 to 7 cm (mean, 3.2 cm), were present in the 34 patients. Strictures were located in the lower common bile duct (n = 22), middle of the common bile duct (n = 6), and hilar confluence (n = 10). In 13 patients (38%) metallic stents were placed at the time of initial biliary drainage (one-stage procedure), while the remaining patients underwent stent placement within 1-7 days of biliary drainage (two-stage procedure). Biliary obstruction was relieved in 31 of 34 patients (91%). Three patients died within 14 days of stent insertion of unrelated causes, without any change in biliary status. Mean duration of follow-up for all patients was 5.3 months (range, 0.5-14 months). Four episodes of stent occlusion occurred in three patients (12% occlusion rate); each episode was treated successfully. The average length of hospital stay for patients who underwent a one-stage procedure was 13 days (range, 3-33 days) and was 20 days (range, 9-42 days) for patients who underwent a two-stage procedure. The facility of one-step insertion, low occlusion rate, and the many strategies available for treatment of occluded stents make metallic stents an attractive alternative to conventional plastic stents in palliating patients with malignant biliary obstruction.     

多支胆管梗阻的介入性引流技术

目的 探讨多支胆管梗阻介入性引流的方法及疗效。方法 ２１例多支胆管梗阻的患者根据不同情况,分别采用左右肝管同时植入支架内引流（１３例）、左右肝管间植入支架经右肝管外引流（３例）、右肝管支架内引流并左肝管外引流（３例）和右前叶肝管支架内引流并右后叶肝管外引流及左肝管内引流或外引流（２例）等内外引流技术进行治疗。结果 ２１例患者共植入胆道内支架３６枚,其中３５枚支架起到良好的内引流作用,１枚因位置不良     

犬胆管金属支架诱导p16、p53基因扩增的实验研究

目的 探讨胆道金属支架在诱导抑癌基因扩增方面的价值.方法 健康成年实验犬24只,采用经皮经肝穿刺胆囊的方法于犬胆总管下段植入支架1枚,术后正常喂养平均半年,再次麻醉后活体开腹取支架覆盖段胆管壁与支架上段胆管壁组织,通过逆转录聚合酶链反应(RT-PCR)方法检测所取组织p16、p53、p15、Bcl-2及K-ras基因的表达情况,计算两个部位胆管壁目的 基因表达阳性率,采用X~2检验进行统计学分析.结果 共20只实验犬建模成功.支架覆盖段胆管壁p16、p53基因表达阳性率分别为80%(16/20)、45%(9/20),支架上段胆管壁p16、p53基因表达阳性率分别为15%(3/20)、0,以上差异具有统计学意义(X~2值分别为16.94、9.17,P值均＜0.05).支架覆盖段胆管壁p15、Bcl-2、K-ras基因表达阳性率分别为60%(12/20)、100%(20/20)、0,支架上段胆管壁p15、Bcl-2、K-ras基因表达阳性率分别为70%(14/20)、100%(20/20)、0,两个部位间差异均无统计学意义(P值均＞0.05).结论 胆管壁p16、p53的扩增加强与胆道金属支架的植入有一定的相关性,对于不存在胆道支架植入禁忌证的恶性梗阻性黄疸患者建议行胆道支架植入术治疗.     

经皮肝胆管穿刺金属内支架植入治疗恶性梗阻性黄疸

目的：探讨经皮肝胆管穿刺金属内支架植入治疗恶性梗阻性黄疸临床应用价值。方法：108例患者中的9r7例均采用X线透视下经皮肝穿刺胆道内支架植入术治疗恶性梗阻性黄疸。根据梗阻部位的不同解剖决定放置支架的方式。结果：108例患者中,90例植入单支支架于肝总管或（和）胆总管,7例植入2支以上支架于总管和分支胆管,11例行外引流。全部患者2周内血清胆红素从（436±314）mol／L降低到（53±31）mol／L。结论：经皮肝穿刺内支架植入是治疗恶性胆道梗阻性的有效方法。     

放置胆管支架与儿童ERCP术后胰腺炎的关系

 目的 探讨放置胆管支架与儿童内镜逆行胰胆管造影(ERCP)术后胰腺炎(PEP)的关系。方法 基于美国国家住院患者样本(NIS)数据库中的儿童患者,使用复杂抽样资料的Logistic回归和多重填补方法进行评价,并根据性别进行亚组分析。结果 放置胆管支架的儿童患者,患PEP的风险较未放置胆管支架的高(OR: 1.44,95% CI: 1.05~1.99,P=0.0246)。亚组分析结果显示,男性儿童放置胆管支架者患PEP风险约为未放置者的1.9倍(OR: 1.89,95% CI: 1.08~3.31,P=0.0262);女性儿童患者未发现放置胆管支架与PEP患病相关联。结论 放置胆管支架与儿童ERCP术后发生PEP风险增加相关,因此对儿童放置胆管支架时,应采取预防措施、停止或更改手术方式等,以降低发生PEP的危险。     

Primary Patency of Wallstents in Malignant Bile Duct Obstruction: Single vs. Two or More Noncoaxial Stents

The purpose of this study was to determine the primary patency of two or more noncoaxial self-expanding metallic Wallstents (Boston Scientific, Natick, MA) and to compare this with the primary patency of a single stent in malignant bile duct obstruction. From August 2002 to August 2004, 127 patients had stents placed for malignant bile duct obstruction. Forty-five patients were treated with more than one noncoaxial self-expanding metallic stents and 82 patients had a single stent placed. Two patients in the multiple-stent group were lost to follow-up. The primary patency period was calculated from the date of stenting until the first poststenting intervention for stent occlusion, death, or the time of last documented follow-up. The patency of a single stent was significantly different from that of multiple stents (P = 0.0004). In the subset of patients with high bile duct obstruction, the patency of a single stent remained significantly different from that of multiple stents (P = 0.02). In the single-stent group, there was no difference in patency between patients with high vs. those with low bile duct obstruction (P = 0.43). The overall median patency for the multistent group and the single-stent group was 201 and 261 days, respectively. In conclusion, the patency of a single stent placed for malignant low or high bile duct obstruction is similar, and significantly longer than, that of multiple stents placed for malignant high bile duct obstruction. Given the median patency of 201 days, when indicated, percutaneous stenting of multiple bile ducts is an effective palliative measure for patients with malignant high bile duct obstruction.     

胆总管末端植入金属支架对肠胆反流的影响

目的 探讨胆总管末端植入金属支架后早期肠胆反流状况和反流性胆管炎的发生机制.方法 16例无胆系感染并排除肠梗阻及肠道、胆道手术病史的恶性低位胆管梗阻患者,通过经皮经肝胆管穿刺及单纯外引流后,于胆总管末端植入金属网状支架.在植入支架前进行血白细胞计数、中性粒细胞百分比和总胆红素、直接胆红素含量的检测.支架植入后2～5 d再次检查上述各项指标,并于拔管前2 h口服含有99锝m-二乙三氨五醋酸(99Tcm-DTPA)的水,2 h后检测胆汁中核素的放射性活度.对研究获得的计量资料,采用配对t检验或秩和检验,P＜0.05为差异有统计学意义.结果 支架植入后2～5 d,14例进行了胆汁99Tcm检测,其中12例于拔管前2 h胆汁中检测到99Tcm活度,放射计数占总摄入剂量的1.82%.2例胆汁中未检测到99Tcm.14例进行胆汁核素检测的患者均没有出现高热、寒战、黄疸加重的胆管炎表现,血白细胞计数和中性粒细胞百分比分别为(7.59±2.62)×109/L、0.74,与支架植入前的(7.94±3.84)×109/L和0.68相比,差异均没有统计学意义(分别为t=0.423、Z=1.036,P值均＞0.05);而血总胆红素和直接胆红素值的中位数分别为92.2和74.3 μmol/L,明显低于支架植入前的202.6和154.7 μmol/L,差异均具有统计学意义(Z值均为-3.170,P值均＜0.05).结论 胆总管末端植入支架后,早期就有较高的肠胆反流发生率,但没有反流性胆管炎的发生.     

恶性胆道梗阻ERCP表现及胆道内支架治疗

目的:评价ERCP在恶性胆道梗阻诊断及胆道内支架治疗的价值。方法:回顾性分析19例恶性胆道梗阻ERCP表现和内支架植入情况。结果:19例恶性胆道梗阻ERCP表现直接征象:胆管截断征9例、不规则偏心性或向心性狭窄9例、不规则充盈缺损1例。间接征象:梗阻近端胆总管中、重度扩张,肝内胆管扩张,呈软藤征;胆囊增大;胰管扩张等。19例共植入支架22个,一次操作成功率95.65%,低位梗阻减黄有效率达92.85%,高位梗阻减黄有效率达80.00%。结论:ERCP对于胆道梗阻定位、定性诊断有很大价值,胆道内支架引流术可以作为恶性胆道梗阻姑息性治疗的首选方法。     

Treatment of common bile duct obstruction by pancreatic cancer using various stents: single-center experience

PURPOSE: To compare the effectiveness of various means of stenting in patients with biliary obstruction caused by pancreatic cancer in a retrospective analysis. METHODS: Sixty-two patients with biliary obstruction due to unresectable pancreatic cancer underwent biliary stenting. On the basis of the findings obtained by percutaneous transhepatic cholangiography (10 patients) and endoscopic retrograde cholangiography (52 patients), the site of obstruction was distal to the hilar confluence, predominantly especially in the middle to lower third of the common bile duct. Polyurethane-covered Wallstents (9 mm in diameter) were inserted in 13 patients, while uncovered Wallstents (10 mm in diameter) were used in 10 patients and plastic stents (10 Fr and 12 Fr) were used in 39 patients. RESULTS: Stenting was successful in 34 patients (87.2%) treated with plastic stents and in 22 patients (95.7%) treated with Wallstents. Effective biliary drainage was achieved in 32 out of 34 patients (94.1%) treated with plastic stents and in 21 out of 22 patients (95.5%) treated with Wallstents. The cumulative patency rate was significantly higher for the uncovered and covered Wallstents compared to plastic stents, but was not significantly higher for covered than for uncovered Wallstents. Stent occlusion occurred in 23 patients (70%; all by clogging) from the plastic stent group, in two patients (22%; by tumor ingrowth) from the uncovered Wallstent group, and in one patient (9%; by clogging) from the covered Wallstent group. The survival rate showed no significant difference among the three stent groups. CONCLUSION: The Wallstent is effective for long-term palliation in patients with obstruction caused by pancreatic cancer invading the middle to lower part of the common bile duct. The covered Wallstent can prevent tumor ingrowth, a problem with the uncovered Wallstent. However, it may be necessary to take measures to prevent the migration or clogging of covered Wallstents.