微创经椎间孔腰椎间融合术联合中药封包疗法治疗腰椎滑脱症的临床研究

Clinical study on minimally invasive transforaminal lumbar interbody fusion combined with traditional Chinese medicine packet therapy for treatment of lumbar spondylolisthesis

目的：观察微创经椎间孔腰椎间融合术（transforaminal lumbar interbody fusion,TLIF）联合中药封包疗法治疗腰椎滑脱症的临床疗效和安全性。方法：回顾性分析116例手术治疗的腰椎滑脱症患者的病例资料。28例采用开放TLIF治疗（TLIF组）、31例采用开放TLIF联合中药封包治疗（TLIF联合组）、27例采用微创TLIF治疗（MIS-TLIF组）、30例采用微创TLIF联合中药封包治疗（MIS-TLIF联合组）。微创TLIF采用CN12M009 Quadrant系统进行手术,中药封包疗法所用药物为消炎散。比较各组的并发症发生情况、手术时间、术中出血量、术后引流量、住院时间、疼痛视觉模拟量表（visual analogue scale,VAS）评分、Oswestry功能障碍指数（Oswestry disability index,ODI）评分、外周静脉血肌酸激酶（creatine kinase,CK）含量及多裂肌横截面积和灰度值。多裂肌横截面积和灰度值采用Image J v2.1软件在腰椎T2WI MRI上进行测量。结果：所有患者均获得随访,随访时间12~24个月。术后TLIF组2例患者出现神经损伤表现,使用神经营养药物治疗后逐渐好转;各组均未发生椎间隙感染、脑脊液漏、下肢深静脉血栓、内固定材料断裂或松动、椎间隙高度丢失、椎体间Cage下陷及移位等并发症。至末次随访时,所有患者腰椎滑脱均已复位,融合椎体均已获得骨性愈合。TLIF组和TLIF联合组手术时间比较,MIS-TLIF组和MIS-TLIF联合组手术时间比较,组间差异均无统计学意义;TLIF组和TLIF联合组手术时间均比MIS-TLIF组和MIS-TLIF联合组长（P=0.000,P=0.000;P=0.000,P=0.000）。TLIF组和TLIF联合组术中出血量比较,MIS-TLIF组和MIS-TLIF联合组术中出血量比较,组间差异均无统计学意义;TLIF组和TLIF联合组术中出血量均比MIS-TLIF组和MIS-TLIF联合组多（P=0.000,P=0.000;P=0.000,P=0.000）。TLIF组和TLIF联合组术后引流量比较,MIS-TLIF组和MIS-TLIF联合组术后引流量比较,组间差异均无统计学意义;TLIF组和TLIF联合组术后引流量均比MIS-TLIF组和MIS-TLIF联合组多（P=0.000,P=0.000;P=0.000,P=0.000）。TLIF组比TLIF联合组住院时间长（P=0.013）,MIS-TLIF组比MIS-TLIF联合组住院时间长（P=0.024）,TLIF组和TLIF联合组住院时间均比MIS-TLIF组和MIS-TLIF联合组长（P=0.000,P=0.000;P=0.000,P=0.000）。手术前后不同时间VAS评分的差异有统计学意义,即存在时间效应（F=1 635.341,P=0.000）。与术前相比,4组患者术后2 d、7 d、14 d、6个月、12个月时的VAS评分均减小（P=0.004,P=0.000,P=0.000,P=0.001;P=0.002,P=0.000,P=0.000,P=0.000;P=0.001,P=0.000,P=0.000,P=0.000;P=0.008,P=0.000,P=0.000,P=0.000;P=0.000,P=0.000,P=0.000,P=0.004）。4组VAS评分总体上比较,组间差异有统计学意义,即存在分组效应（F=129.520,P=0.000）。术前4组VAS评分比较,差异无统计学意义;术后2 d时,MIS-TLIF组和MIS-TLIF联合组VAS评分均小于TLIF组和TLIF联合组（P=0.000,P=0.000;P=0.000,P=0.000）;TLIF组与TLIF联合组比较、MIS-TLIF组与MIS-TLIF联合组比较,组间差异均无统计学意义;术后7 d、14 d、6个月、12个月时,MIS-TLIF联合组VAS评分均小于MIS-TLIF组（P=0.000;P=0.000;P=0.000;P=0.000）,MIS-TLIF组VAS评分均小于TLIF联合组（P=0.000;P=0.000;P=0.000;P=0.003）,TLIF联合组的VAS评分均小于TLIF组（P=0.000;P=0.000;P=0.000;P=0.006）;时间因素与分组因素存在交互效应（F=18.500,P=0.000）。手术前后不同时间ODI评分的差异有统计学意义,即存在时间效应（F=2 857.334,P=0.000）。与术前相比,4组患者术后2 d、7 d、14 d、6个月、12个月时的ODI评分均减小（P=0.013,P=0.000,P=0.000,P=0.003;P=0.008,P=0.000,P=0.000,P=0.001;P=0.003,P=0.000,P=0.000,P=0.002;P=0.005,P=0.000,P=0.000,P=0.000;P=0.000,P=0.000,P=0.000,P=0.031）。4组ODI评分总体上比较,组间差异有统计学意义,即存在分组效应（F=173.869,P=0.000）。术前4组ODI评分比较,差异无统计学意义;术后2 d时,MIS-TLIF组和MIS-TLIF联合组的ODI评分均小于TLIF组和TLIF联合组（P=0.000,P=0.003;P=0.000,P=0.000）;TLIF组与TLIF联合组比较、MIS-TLIF组与MIS-TLIF联合组比较,组间差异均无统计学意义;术后7 d、14 d、6个月、12个月时,MIS-TLIF联合组ODI评分均小于MIS-TLIF组（P=0.000;P=0.000;P=0.003;P=0.000）,MIS-TLIF组ODI评分均小于TLIF联合组（P=0.000;P=0.000;P=0.006;P=0.000）,TLIF联合组的ODI评分均小于TLIF组（P=0.004;P=0.000;P=0.002;P=0.000）。时间因素与分组因素存在交互效应（F=23.108,P=0.000）。手术前后不同时间外周静脉血CK含量的差异有统计学意义,即存在时间效应（F=5 355.427,P=0.000）。与术前相比,4组患者术后2 d、7 d、14 d、6个月时外周静脉血CK含量均增加（P=0.002,P=0.000,P=0.000,P=0.000;P=0.002,P=0.000,P=0.000,P=0.007;P=0.000,P=0.000,P=0.000,P=0.012;P=0.008,P=0.000,P=0.000,P=0.000）。4组外周静脉血CK含量总体上比较,组间差异有统计学意义,即存在分组效应（F=662.238,P=0.000）。术前及术后6个月时4组外周静脉血CK含量比较,差异均无统计学意义;术后2 d时,MIS-TLIF组和MIS-TLIF联合组的CK含量均小于TLIF组和TLIF联合组（P=0.002,P=0.006;P=0.000,P=0.000）;TLIF组与TLIF联合组比较、MISTLIF组与MIS-TLIF联合组比较,组间差异均无统计学意义;术后7 d、14 d时,MIS-TLIF联合组的CK含量均小于MIS-TLIF组（P=0.000;P=0.000）,MIS-TLIF组的CK含量均小于TLIF联合组（P=0.000;P=0.009）,TLIF联合组的CK含量均小于TLIF组（P=0.008;P=0.000）。时间因素与分组因素存在交互效应（F=133.581,P=0.000）。手术前后不同时间多裂肌横截面积的差异有统计学意义,即存在时间效应（F=4 633.716,P=0.000）。与术前相比,4组患者术后14 d、6个月、12个月时多裂肌横截面积均减小（P=0.002,P=0.000,P=0.000,P=0.000;P=0.001,P=0.000,P=0.000,P=0.025;P=0.001,P=0.000,P=0.000,P=0.000）。4组多裂肌横截面积总体上比较,组间差异有统计学意义,即存在分组效应（F=849.382,P=0.000）。术前4组多裂肌横截面积比较,差异无统计学意义;术后14 d、6个月、12个月时,MIS-TLIF联合组的多裂肌横截面积均大于MIS-TLIF组（P=0.006;P=0.000;P=0.000）,MIS-TLIF组的多裂肌横截面积均大于TLIF联合组（P=0.000;P=0.000;P=0.000）,TLIF联合组的的多裂肌横截面积均大于TLIF组（P=0.000;P=0.000;P=0.000）。时间因素与分组因素存在交互效应（F=155.619,P=0.000）。手术前后不同时间多裂肌灰度值的差异有统计学意义,即存在时间效应（F=2 679.510,P=0.000）。与术前相比,4组患者术后14 d、6个月、12个月时多裂肌灰度值均减小（P=0.009,P=0.000,P=0.000,P=0.000;P=0.008,P=0.000,P=0.000,P=0.000;P=0.004,P=0.000,P=0.000,P=0.024）。4组多裂肌灰度值总体上比较,组间差异有统计学意义,即存在分组效应（F=453.201,P=0.000）。术前4组多裂肌灰度值比较,差异无统计学意义;术后14 d、6个月、12个月时,MIS-TLIF联合组的多裂肌灰度值均大于MIS-TLIF组（P=0.002;P=0.000;P=0.000）,MIS-TLIF组的多裂肌灰度值均大于TLIF联合组（P=0.000;P=0.000;P=0.000）,TLIF联合组的多裂肌灰度值均大于TLIF组（P=0.000;P=0.000;P=0.000）。时间因素与分组因素存在交互效应（F=56.039,P=0.000）。结论：采用微创TLIF联合中药封包疗法治疗腰椎滑脱症具有安全性好、创伤小、住院时间短、术后疼痛轻、恢复快等优点,值得临床推广应用。

Objective： To observe the clinical curative effects and safety of minimally invasive transforaminal lumbar interbody fusion（ TLIF） combined with traditional Chinese medicine（ TCM） packet therapy in the treatment of lumbar spondylolisthesis. Methods： The medical records of 116 patients with lumbar spondylolisthesis were analyzed retrospectively. Twenty- eight patients were treated with open TLIF（ TLIF group）,thirty- one patients were treated with open TLIF combined with TCM packet therapy（ TLIF combined- treatment group）,twenty- seven patients were treated with minimally invasive TLIF（ MIS- TLIF group）,while the others were treated with MIS-TLIF combined with TCM packet therapy（ MIS- TLIF combined- treatment group）. CN12M009 Quadrant system was used for MIS- TLIF surgery,and Xiaoyan San（ 消炎散） was used for TCM packet therapy. The complications,operative times,intraoperatve blood loss,postoperative drainage,hospital stay,pain visual analogue scale（ VAS） scores,Oswestry disability index（ ODI） scores,peripheral venous blood creatine kinase（ CK） contents and cross sectional areas（ CSA） and gray values of multifidus were compared between the 4 groups. The CSA and gray values of multifidus were measured by using Image J v2. 1 software on T2- weighted MRI of lumbar spine. Results： All patients in the4 groups were followed up for 12- 24 months. Nerve injuries were found in 2 patients in TLIF group after surgery,and the patients improved gradually after treatment with neurotrophic drugs. No complications such as intervertebral space infection,cerebrospinal fluid leakage,lower extremity deep venous thrombosis,breakage or loosening of internal fixators,loss of interspace height loss and sag and displacement of intervertebral cage were found in all of the groups. All patients obtained reduction of lumbar spondylolisthesis and bone union of fused vertebra at last follow- up. There was no statistical difference in operative time between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. The operative time was longer in TLIF group and TLIF combined-treatment group compared to MIS- TLIF group and MIS- TLIF combined- treatment group（ P = 0. 000,P = 0. 000; P = 0. 000,P =0. 000）. There was no statistical difference in intraoperatve blood loss between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. The intraoperatve blood loss were more in TLIF group and TLIF combined- treatment group compared to MIS- TLIF group and MIS- TLIF combined- treatment group（ P = 0. 000,P = 0. 000; P = 0. 000,P =0. 000）. There was no statistical difference in postoperative drainage between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. The postoperative drainage were more in TLIF group and TLIF combined-treatment group compared to MIS- TLIF group and MIS- TLIF combined- treatment group（ P = 0. 000,P = 0. 000; P = 0. 000,P =0. 000）. The hospital stay was longer in TLIF group compared to TLIF combined- treatment group（ P = 0. 013） and was longer in MIS-TLIF group compared to MIS- TLIF combined- treatment group（ P = 0. 024）,and was longer in TLIF group and TLIF combined- treatment group compared to MIS- TLIF group and MIS- TLIF combined- treatment group（ P = 0. 000,P = 0. 000; P = 0. 000,P = 0. 000）.There was statistical difference in VAS scores between different timepoints before and after the surgery,in other words,there was time effect（ F = 1 635. 341,P = 0. 000）. The VAS scores decreased in all of the 4 groups at 2,7,14 days and 6 and 12 months after the surgery compared to pre- surgery（ P = 0. 004,P = 0. 000,P = 0. 000,P = 0. 001; P = 0. 002,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 001,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 008,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 000,P = 0. 000,P = 0. 000,P = 0. 004）. There was statistical difference in VAS scores between the 4 groups in general,in other words,there was group effect（ F = 129. 520,P = 0. 000）. There was no statistical difference in VAS scores between the 4 groups before surgery. The VAS scores were lower in MIS- TLIF group and MIS- TLIF combined- treatment group compared to TLIF group and TLIF combined- treatment group at 2 days after the surgery（ P = 0. 000,P =0. 000; P = 0. 000,P = 0. 000）. There was no statistical difference in VAS scores between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. At 7,14 days and 6 and 12 months after the surgery,the VAS scores were lower in MIS- TLIF combined- treatment group compared to MIS- TLIF group（ P = 0. 000; P = 0. 000; P = 0. 000; P =0. 000）,and were lower in MIS- TLIF group compared to TLIF combined- treatment group（ P = 0. 000; P = 0. 000; P = 0. 000; P =0. 003）,and were lower in TLIF combined- treatment group compared to TLIF group（ P = 0. 000; P = 0. 000; P = 0. 000; P = 0. 006）.There was interaction between time factor and grouping factor（ F = 18. 500,P = 0. 000）. There was statistical difference in ODI scores between different timepoints before and after the surgery,in other words,there was time effect（ F = 2 857. 334,P = 0. 000）. The ODI scores decreased in all of the 4 groups at 2,7,14 days and 6 and 12 months after the surgery compared to pre- surgery（ P = 0. 013,P = 0. 000,P = 0. 000,P = 0. 003; P = 0. 008,P = 0. 000,P = 0. 000,P = 0. 001; P = 0. 003,P = 0. 000,P = 0. 000,P = 0. 002; P = 0. 005,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 000,P = 0. 000,P = 0. 000,P = 0. 031）. There was statistical difference in ODI scores between the 4 groups in general,in other words,there was group effect（ F = 173. 869,P = 0. 000）. There was no statistical difference in ODI scores between the 4groups before surgery. At 2 days after the surgery,the ODI scores were lower in MIS- TLIF group and MIS- TLIF combined- treatment group compared to TLIF group and TLIF combined- treatment group（ P = 0. 000,P = 0. 003; P = 0. 000,P = 0. 000）,and there was no statistical difference in ODI scores between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. At 7,14 days and 6 and 12 months after the surgery,the ODI scores were lower in MIS- TLIF combined-treatment group compared to MIS- TLIF group（ P = 0. 000; P = 0. 000; P = 0. 003; P = 0. 000）,and were lower in MIS- TLIF group compared to TLIF combined- treatment group（ P = 0. 000; P = 0. 000; P = 0. 006; P = 0. 000）,and were lower in TLIF combined- treatment group compared to TLIF group（ P = 0. 004; P = 0. 000; P = 0. 002; P = 0. 000）. There was interaction between time factor and grouping factor（ F = 23. 108,P = 0. 000）. There was statistical difference in peripheral venous blood CK contents between different timepoints before and after the surgery,in other words,there was time effect（ F = 5 355. 427,P = 0. 000）. The peripheral venous blood CK contents increased in all of the 4 groups at 2,7,14 days and 6 months after the surgery compared to pre- surgery（ P = 0. 002,P = 0. 000,P = 0. 000,P =0. 000; P = 0. 002,P = 0. 000,P = 0. 000,P = 0. 007; P = 0. 000,P = 0. 000,P = 0. 000,P = 0. 012; P = 0. 008,P = 0. 000,P = 0. 000,P =0. 000）. There was statistical difference in peripheral venous blood CK contents between the 4 groups in general,in other words,there was group effect（ F = 662. 238,P = 0. 000）. There was no statistical difference in peripheral venous blood CK contents between the 4 groups before surgery and at 6 months after the surgery. At 2 days after the surgery,the peripheral venous blood CK contents were lower in MIS-TLIF group and MIS- TLIF combined- treatment group compared to TLIF group and TLIF combined- treatment group（ P = 0. 002,P =0. 006; P = 0. 000,P = 0. 000） and there was no statistical difference between TLIF group and TLIF combined- treatment group and between MIS- TLIF group and MIS- TLIF combined- treatment group. At 7 and 14 days after the surgery,the peripheral venous blood CKcontents were lower in MIS- TLIF combined- treatment group compared to MIS- TLIF group（ P = 0. 000; P = 0. 000）,and were lower in MIS- TLIF group compared to TLIF combined- treatment（ P = 0. 000; P = 0. 009）,and were lower in TLIF combined- treatment group compared to TLIF group（ P = 0. 008; P = 0. 000）. There was interaction between time factor and grouping factor（ F = 133. 581,P = 0. 000）.There was statistical difference in the CSA of multifidus between different timepoints before and after the surgery,in other words,there was time effect（ F = 4 633. 716,P = 0. 000）. The CSA of multifidus decreased in all of the 4 groups at 14 days and 6 and 12 months after the surgery compared to pre- surgery（ P = 0. 002,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 001,P = 0. 000,P = 0. 000,P = 0. 025; P = 0. 001,P = 0. 000,P = 0. 000,P = 0. 000）. There was statistical difference in the CSA of multifidus between the 4 groups in general,in other words,there was group effect（ F = 849. 382,P = 0. 000）. There was no statistical difference in the CSA of multifidus between the 4 groups before surgery. At 14 days and 6 and 12 months after the surgery,the CSA of multifidus were greater in MIS- TLIF combined- treatment group compared to MIS- TLIF group（ P = 0. 006; P = 0. 000; P = 0. 000）,and were greater in MIS- TLIF group compared to TLIF combined- treatment group（ P = 0. 000; P = 0. 000; P = 0. 000）,and were greater in TLIF combined- treatment compared to TLIF group（ P =0. 000; P = 0. 000; P = 0. 000）. There was interaction between time factor and grouping factor（ F = 155. 619,P = 0. 000）. There was statistical difference in the gray values of multifidus between different timepoints before and after the surgery,in other words,there was time effect（ F = 2 679. 510,P = 0. 000）. The gray values of multifidus decreased in all of the 4 groups at 14 days and 6 and 12 months after the surgery compared to pre- surgery（ P = 0. 009,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 008,P = 0. 000,P = 0. 000,P = 0. 000; P = 0. 004,P = 0. 000,P = 0. 000,P = 0. 024）. There was statistical difference in the gray values of multifidus between the 4 groups in general,in other words,there was group effect（ F = 453. 201,P = 0. 000）. There was no statistical difference in the gray values of multifidus between the 4groups before surgery. At 14 days and 6 and 12 months after the surgery,the gray values of multifidus were greater in MIS- TLIF combined- treatment group compared to MIS- TLIF group（ P = 0. 002; P = 0. 000; P = 0. 000）,and were greater in MIS- TLIF group compared to TLIF combined- treatment group（ P = 0. 000; P = 0. 000; P = 0. 000）,and were greater in TLIF combined- treatment group compared to TLIF group（ P = 0. 000; P = 0. 000; P = 0. 000）. There was interaction between time factor and grouping factor（ F = 56. 039,P = 0. 000）.Conclusion： The combination therapy of minimally invasive TLIF and TCM packet therapy has such advantages as high safety,less trauma,short hospital stay,less postoperative pain and fast recovery in treatment of lumbar spondylolisthesis,so it is worthy of popularizing in clinic.