经皮穿刺射频消融治疗椎体肿瘤的实验和临床研究
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摘要
目的一、通过对离体及活体猪椎体进行射频消融(radiofrequency ablation RFA),观察其骨质凝固性坏死范围及热场分布,探讨椎体RFA时脊髓的安全性以及椎体周围有无软组织损伤；二、RFA后,通过对活体标本的病理切片分析,观察其破坏程度及修复过程；三、对离体及活体RFA时热场分布进行比较,分析消融过程中椎体骨质内流动的血液及椎管内流动的脑脊液对消融局部温度的影响;四、对椎体血管瘤及椎体转移性肿瘤患者行RFA联合椎体成形术,评价患者临床症状、神经功能检查的缓解程度及生活质量的改善情况。方法一、离体实验部分：取30节新鲜成年猪椎体,随机分成两组。电极针深度分别为l0mm,20mmm。消融达稳态后按预先设计测温点测温。消融20分钟后,沿电极针轴位平面切开观察骨质凝固范围。二、活体实验部分：对两头小型香猪椎体行射频术,一头消融两个椎体后立即取标本行病理切片制作。第二头每周消融两个椎体,五周共消融10个椎体,第六周取标本行病理切片制作。每个椎体消融时按预先设计的测温点测消融0时刻、消融5分钟、10分钟、15分钟、20分钟各测温点的温度值。三、临床病例部分：对三例椎体转移瘤患者及一例椎体血管瘤患者行RFA及椎体成形术(percutaneous vertebroplasty, PVP),术前、术后24小时、48小时、一周、两周、四周,观察随访,进行VAS评分及WHO疼痛分级疗效评定。结果一、离体实验部分：各测温点在3.5分钟达稳态。靠电极越近温度上升越快。两组椎体周围软组织无损伤,当电极针深入椎体l0mm无脊髓损伤,电极针深入椎体20mmm可能会有脊髓损伤。两组测温点组内差异显著(p<0.05)。二、活体实验部分：各测温点0时刻温度值差异无显著意义(p>0.05)。当消融5分钟后电极针尖温度达到90℃以上时,各测温点的温度值差异有统计学意义(p<0.05)。电极针尖及椎体骨质内深1Omm位置的温度在消融5分钟后所测得的值明显高于椎体后壁及椎体的骨皮质表面,但各测温点的温度值均有升高,均高于0时刻各测温点的温度值。椎体骨质内深10mm位置的温度在消融5分钟后四个记录时刻的组内比较差异有统计学意义(p<0.05),温度总体上呈渐升的过程。椎体后壁消融5分钟后四个记录时刻的温度组内比较差异无统计学意义(p>0.05)。椎体骨皮质表面四个记录时刻的温度组内比较差异同样无统计学意义(p>0.05)。骨质破坏区消融后第二周开始纤维修复,第五周骨性骨痂修复及骨小梁贯穿。三、临床病例部分：术前术后神经系统检查,评价神经脊髓功能,术前VAS评分与术后各时间分值进行配对资料t检验,差异均有统计学意义(P<0.01),术后患者疼痛症状较术前明显改善,尤其术后一周VAS评分明显降低。术前疼与术后各时间WHO疼痛分级进行配对资料t检验,差异均有统计学意义(P<0.01)。结论1、在对椎体行RFA时,椎管内流动的脑脊液及椎体骨质内流动的血液会带走部分热量,骨皮质具有一定的隔热作用；2、对骨皮质保持完整的椎体行RFA时,不会引起神经、脊髓及周围软组织损伤；3、在活体动物实验中,椎体RFA后第二周开始纤维修复,第五周骨性骨痂修复及骨小梁贯穿。4、由于椎体RFA后,会引起椎体内部组织坏死,残留空腔,利于骨水泥充分分布。5、对椎体后壁被破坏的椎体转移性肿瘤或血管瘤RFA及PVP时,术前必须准确评估,术中谨慎操作,防止脊髓热损伤及骨水泥泄露压迫脊髓或神经根。6、RFA联合PVP可以有效缓解患者因椎体转移性肿瘤或椎体血管瘤引起的顽固性疼痛,提高生活质量。7、对椎体转移性肿瘤或血管瘤行RFA联合PVP可以有效预防椎体压缩性骨折和或患者截瘫。
Objective First, To carry out ex vivo and in vivo porcine vertebral radio frequency ablation, observe the scope of its bone coagulation and thermal field distribution. Explore the security of the spinal cord and availability of soft tissue injury around the vertebral when radiofrequency ablation. Second, after radiofrequency ablation, through the biopsy specimens of pathological section analysis, to observe the damage degree and repair process. Third, to compare ex vivo with in vivo thermal field distribution when radio frequency, analyze the effection of the flow of blood in vertebral bone and the flow of cerebrospinal fluid in vertebral canal on the process of ablation to local temperature. Fourth, to patient who suffer with vertebral metastases or vertebral hemangioma treated with radiofrequency ablation combined with vertebroplasty. Evaluation of clinical symptoms relief of pain degree and quality of life improvements and nerve function. Methods First, ex vivo experiment: 30 fresh adult porcine vertebrae were randomly divided into two groups. The depth of the needle electrodes were 10mm,20mm.After reach steady-state ablation According to the pre-designed temperature-point measure temperature. After ablation 20 minutes, along the electrode needle axial plane cut to observe the scope of coagulation area. Second, in vivo experiment:radiofrequency ablation ten vertebrae in 5 weeks.the one fetch two vertebral biopsy specimens make pathological section after ablation immediately. another ablation of ten vertebrae ablation of two vertebrae every week.,fetch all experimental vertebral biopsy specimens make pathological section on the sixth week. Every vertebrae according to the pre-designed temperature-point measure 0 times, ablation 5 minutes,10 minutes,15 minutes,20 minutes temperature. Third, clinical Cases:On three cases of vertebral metastases and one case of vertebral hemangiomas treated with radiofrequency ablation and vertebroplasty, preoperative and postoperative 24 hours、48 hours、one week、two weeks、four weeks to observe the follow-up, conduct the evaluation of VAS pain score and the classification of WHO pain treat efficacy. Results First, ex vivo experiment: the temperature in 3.5 minutes reached steady-state. Electrode on more recent the temperature rise more sooner. two groups were no around vertebral soft tissue injury. When the electrode needle depth 10mm without spinal cord injury,20mm deep needle electrode may have spinal cord injury. The temperature in two groups were different significantly (p＜0.05). Second, in vivo experiment:each temperature measuring point on "0" times was not significant difference (p> 0.05). After ablation 5 minutes,the ablation electrode tip temperature reach above 90℃,each temperature measurement point temperature difference was statistically significant (p＜0.05). Electrode tip and the vertebral bone position within 1cm deep in the melting temperature measured after 5 minutes was significantly higher than the value of the posterior vertebral body and vertebral bone cortex surface,but the temperature measurement points are increased and higher than 0 time each point of the measurement temperature.1cm deep within the vertebral bone position after 5 minutes the temperature in the melting point of the group of four record the difference was statistically significant (p＜0.05), The temperature was gradually rise process in the overall. After ablation 5 minutes, the temperature on posterior vertebral wall of the four records showed no significant difference compared in group(p> 0.05).Vertebral bone cortex surface temperature of four records also records showed no significant difference compared in group(p> 0.05). the second week after RFA vertebral fiber repair, the fifth week of repair of bone and trabecular bone throughout the callus. Third, clinical Cases:Preoperative and postoperative the evalution of VAS score for each time paired t test, the differences were statistically significant (P＜0.01). Postoperation, the patient pain symptom was significantly relieved compared with preoperation. VAS score decreased significantly especially after postoperative one week. Preoperative and postoperative the classification of WHO pain treat efficacy for each time paired t test, the differences were statistically significant (P＜0.01). Conclusion First, radiofrequency ablation the vertebrae, the cerebrospinal fluid flow in the spinal canal and the flow of blood in the vertebrae will take away some of the heat; bone cortex has some insulate function. Second, maintain the integrity of the vertebral cortical line of radiofrequency ablation will not lead to nerve, spinal cord and soft tissue injury. Third, In vivo experiments, the second week after RFA vertebral fiber repair, the fifth week of repair of bone and trabecular bone throughout the callus. Fourth, as the vertebral body after radiofrequency ablation, would lead to vertebral body necrosis, residual cavity, which will help polymtthy methacrylate full distribution. Fifth, radiofrequency ablation and vertebroplasty for the destruction of the posterior vertebral body with vertebral metastasis or vascular tumor need evaluate exactly on preoperation,be careful on operation, prevent polymtthy methacrylate leakage to compress spinal cord or nerve root. Sixth, radiofrequency ablation combined with vertebroplasty can relieve patient due to vertebral metastases or vertebral hemangiomas caused intractable pain, improve quality of life. Seventh, radiofrequency ablation combined with vertebroplasty treat the vertebral metastasis or hemangioma patient can be effective in preventing vertebral compression fractures or/and paraplegia.
Objective First, To carry out ex vivo and in vivo porcine vertebral radio frequency ablation, observe the scope of its bone coagulation and thermal field distribution. Explore the security of the spinal cord and availability of soft tissue injury around the vertebral when radiofrequency ablation. Second, after radiofrequency ablation, through the biopsy specimens of pathological section analysis, to observe the damage degree and repair process. Third, to compare ex vivo with in vivo thermal field distribution when radio frequency, analyze the effection of the flow of blood in vertebral bone and the flow of cerebrospinal fluid in vertebral canal on the process of ablation to local temperature. Fourth, to patient who suffer with vertebral metastases or vertebral hemangioma treated with radiofrequency ablation combined with vertebroplasty. Evaluation of clinical symptoms relief of pain degree and quality of life improvements and nerve function. Methods First, ex vivo experiment: 30 fresh adult porcine vertebrae were randomly divided into two groups. The depth of the needle electrodes were 10mm,20mm.After reach steady-state ablation According to the pre-designed temperature-point measure temperature. After ablation 20 minutes, along the electrode needle axial plane cut to observe the scope of coagulation area. Second, in vivo experiment:radiofrequency ablation ten vertebrae in 5 weeks.the one fetch two vertebral biopsy specimens make pathological section after ablation immediately. another ablation of ten vertebrae ablation of two vertebrae every week.,fetch all experimental vertebral biopsy specimens make pathological section on the sixth week. Every vertebrae according to the pre-designed temperature-point measure 0 times, ablation 5 minutes,10 minutes,15 minutes,20 minutes temperature. Third, clinical Cases:On three cases of vertebral metastases and one case of vertebral hemangiomas treated with radiofrequency ablation and vertebroplasty, preoperative and postoperative 24 hours、48 hours、one week、two weeks、four weeks to observe the follow-up, conduct the evaluation of VAS pain score and the classification of WHO pain treat efficacy. Results First, ex vivo experiment: the temperature in 3.5 minutes reached steady-state. Electrode on more recent the temperature rise more sooner. two groups were no around vertebral soft tissue injury. When the electrode needle depth 10mm without spinal cord injury,20mm deep needle electrode may have spinal cord injury. The temperature in two groups were different significantly (p＜0.05). Second, in vivo experiment:each temperature measuring point on "0" times was not significant difference (p> 0.05). After ablation 5 minutes,the ablation electrode tip temperature reach above 90℃,each temperature measurement point temperature difference was statistically significant (p＜0.05). Electrode tip and the vertebral bone position within 1cm deep in the melting temperature measured after 5 minutes was significantly higher than the value of the posterior vertebral body and vertebral bone cortex surface,but the temperature measurement points are increased and higher than 0 time each point of the measurement temperature.1cm deep within the vertebral bone position after 5 minutes the temperature in the melting point of the group of four record the difference was statistically significant (p＜0.05), The temperature was gradually rise process in the overall. After ablation 5 minutes, the temperature on posterior vertebral wall of the four records showed no significant difference compared in group(p> 0.05).Vertebral bone cortex surface temperature of four records also records showed no significant difference compared in group(p> 0.05). the second week after RFA vertebral fiber repair, the fifth week of repair of bone and trabecular bone throughout the callus. Third, clinical Cases:Preoperative and postoperative the evalution of VAS score for each time paired t test, the differences were statistically significant (P＜0.01). Postoperation, the patient pain symptom was significantly relieved compared with preoperation. VAS score decreased significantly especially after postoperative one week. Preoperative and postoperative the classification of WHO pain treat efficacy for each time paired t test, the differences were statistically significant (P＜0.01). Conclusion First, radiofrequency ablation the vertebrae, the cerebrospinal fluid flow in the spinal canal and the flow of blood in the vertebrae will take away some of the heat; bone cortex has some insulate function. Second, maintain the integrity of the vertebral cortical line of radiofrequency ablation will not lead to nerve, spinal cord and soft tissue injury. Third, In vivo experiments, the second week after RFA vertebral fiber repair, the fifth week of repair of bone and trabecular bone throughout the callus. Fourth, as the vertebral body after radiofrequency ablation, would lead to vertebral body necrosis, residual cavity, which will help polymtthy methacrylate full distribution. Fifth, radiofrequency ablation and vertebroplasty for the destruction of the posterior vertebral body with vertebral metastasis or vascular tumor need evaluate exactly on preoperation,be careful on operation, prevent polymtthy methacrylate leakage to compress spinal cord or nerve root. Sixth, radiofrequency ablation combined with vertebroplasty can relieve patient due to vertebral metastases or vertebral hemangiomas caused intractable pain, improve quality of life. Seventh, radiofrequency ablation combined with vertebroplasty treat the vertebral metastasis or hemangioma patient can be effective in preventing vertebral compression fractures or/and paraplegia.
引文
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1, 田建明,CT引导下经皮肿瘤消融术应用现状。介入放射学杂志,2007,16(12)：793-795。
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1, 田建明,CT引导下经皮肿瘤消融术应用现状。介入放射学杂志,2007,16(12)：793-795。
2, 邵培坚,周泽健,李伟科,等肢体骨肉瘤介入性综合治疗远期疗效分析。中华放射学杂志,2004,38(10)：1034～1037.
3, 王晋,沈靖南,韩土英,等。84例骨肉瘤生存分析。中国肿瘤临床,2002,29(4)：245-248。
4, Picci p, Bacci G, Ferrari S, et al Local recurrence after limb salvage pro-cedures for osteosarcoma:Crrelation with margins and chemot herapy induced necrosis J Bone Joint Surg(Am),1993,57 (suppl2) 211
5, Jaffe N, Patel SR, Beniamin RS Chemotheraoy in osteosarcoma Basis for application and antagonism to implementation:Early controversies surrounding it simplementation Hematol Oncol Clin North Am,1995,9(4):825.
6, Trapeznikov NN, Aliev MD, MacHak GN, et al Treatment of limb osteosarcoma at the tum of the century (half century of experience in rsearch). Vestnik Rossiiskoi Akademii Meditsinskikh Nauk/Rossiiskaia Akademii Meditsinskikh Nauk,2001, (9):46.
7, Glukhovskaia LLU. The application of intraarterial chemotherapy for the treatment of osteogenic sarcoma in children Naukove Tovarystvo Khirurhiv Ukrainy,1997, (2):12.
8, 陈航,陈义雄。动脉内灌注化疗及栓塞治疗骨与软组织恶性肿瘤的临床与病理观察。中国基层医药,2006,13(7)：1100-1101.
9, 赵增仁,晚期恶性骨肿瘤介入治疗的近期临床疗效观察。现代中西医结合杂志,2003,12(20)：2173.
10, Daniel D and Crawford J. Myelotoxicity from chemotherapy. Semin Oncol 2006,33(1):74-85.
11, Weycker D, Malin J, Edelsberg J, Glass A, Gokhale M, and Oster G Cost of neutropenic complications of chemotherapy. Ann Oncol 2008 19(3):454-460.
12, Go RS and Adjei AA. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin. J Cin Oncol 199917(1):409-422.
13, BC Cancer Agency. Cancer Drug Manual. British Columbia Agency.2006
14, Bikul Das, Roula Antoon等.Squalence selectively protects mouse bone mawow progenitors against cisplatin and carboplatin-induced cytotoxicity in vivo without protecting tumor growth Neoplasia 2008,10(10):1105-1119.
15, Breslau J, Eskridge JM. Preoperative embolization of spine tumors J Vasc Interv Radiol,1995, (6):871.
16,0 Reilly GV. Kleefield J. Klein LA, et al Embolization of solitary spinal meatstases from renal cell carcinoma:Altemative therapy for spinal cord or nerve root compression Surg Neurol,1989,3 (1):268.
17, Nagata Y. Nakano Y. Abe M, et al Osseousmetastases from hepatocellular carcinoma: Embolization for pain control Cardiovase Intervent Radiol,1989,1 (2):149.
18,Wittig JC, Bickels, Priebat D, et al. Osteosarcoma:a multidisciplinary approach to diagnosis and treatment. Am Fam physician,2002,65(6):1123-1132.
19, Cai YB, Niu XH, Zhang Q, et al. Long-term results of combined therapy for primary osteosarcoma in extrimities. Chin J Surg(Chinese),2000,38(5):329-331.
20, Jensen ME, Kallmes DE. Percutaneous vertebroplasty in the treatment of malignant spine disease [J].Caner J,2002,8:194-206.
21, Murphy KJ, Deramond H. Percutaneous vertebroplasty in benign and malignant disease[J]. Neuroimaging Clin N Am,2000,10:535-545.
22, 张贵祥,陆军,潘纪青,等。经皮穿刺椎体成形术的临床应用价值[J]。中华放射学杂志,2002,36： 300-304.
23, Gazelle GS, Goldberg SN, Solbiati L, Livraghi T. Tumor ablation with radio-frequency energy. Radiology 2000; 217:633-646.
24,Gangi A, Kaster B, Klinkert A, Dietemann JL. Injection of alcohol into bone metastases under CT guidance. J Comput Assist Tomogr 1994:18:932-935.
25,Manjubala I,Sastry TP, Kumar RV. J Hiomater Appl,2005 19(4):341-360.
26, L. Thanos. S.Mylona. P. Galani. D. Tzavoulis. V. Kalioras. S. Tanteles. M. Pomoni. Padiofrequency ablation of osseous metastases for the palliation of pain Skeletal Radiol 2008 37:189-194.
27, B. A. Georgy W.Wong. Plasma-Mediated radiofrequency ablation assisted percutaneous cement injection for treating advanced malignant vertebral compression fractures Original research.2007,28:700-705.