肝癌射频消融术后MDCT评价与病理表现的对照研究:动物实验与临床
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摘要
目的观察兔肝VX2肿瘤RFA术后的MDCT平扫和常规三期动态扫描及灌注扫描表现,比较肿瘤RFA术后不同时间点残余肿瘤与治疗反应带之间的增强扫描各期相CT值和灌注扫描各参数值差异,并分析两种扫描方法对于肿瘤RFA术后残瘤和治疗反应带的鉴别价值。观察肝细胞癌RFA术后的MDCT平扫和常规三期动态扫描及灌注扫描表现,比较RFA术后不同时间点内肿瘤残余/局部再发、肝内远处再发和治疗反应带之间的增强扫描各期相CT值和灌注扫描各参数值差异,并初步探讨两种检查方法对于肝癌RFA术后肿瘤与治疗反应带的鉴别价值。
     资料与方法将24只肝VX2瘤兔分为4组,每组6只,分别行RFA治疗。对上述4组瘤兔分别在射频治疗后的第1天、3天、7天和14天行CT平扫和常规动态三期增强扫描及灌注扫描,并于影像检查后处死瘤兔,取病理学标本以备与影像学对照。观察灌注扫描的TDC曲线形态、各灌注参数(BF、BV、MTT、PS和HAF)的伪彩图,在上述4个时间点比较残余肿瘤与射频治疗反应带之间的平扫和三期增强扫描的CT值差异及各灌注参数值差异,以确定CT增强的哪些期相和CT灌注扫描中哪些灌注参数在何时间点对于残余肿瘤和炎性反应带具有鉴别诊断意义。
     对36例临床确诊的肝细胞癌共45个瘤灶行RFA治疗,在RFA治疗后的1天、1月、3月、6月和1年5个时间点行肝脏CT动态三期增强检查和CT灌注扫描,每个时间点上行两种CT扫描方式的病例数分别为21、22、16、16、23例。应用CT常规增强检查和灌注检查,将肿瘤肿瘤残余/局部再发、肝内远处再发分别同炎性反应带和瘤周正常肝组织进行比较,对其各期相CT值和各灌注参数进行对比,从而判断两种扫描方式对肿瘤和炎症、瘤周正常肝的鉴别是否有显著差异,那种方法更具有诊断价值。
     结果CT三期增强检查中,1天和3天组残余肿瘤与炎性反应带的各期CT值比较均无统计学差异;而在7天组中动脉期、门静脉期和14天组中动脉期CT值均有显著差异。残余肿瘤与炎性反应带灌注参数比较,其中血流量(BF)值在各时间点均有统计学差异,血容量(BV)值和肝动脉指数(HAF)值除在7天组无统计学意义外,其余三个时间点均有统计学差异。综合4个时间组数据,经曲线下面积(ROC)分析,BF、BV、HAF三个灌注参数对于残余肿瘤与炎性反应带的鉴别有统计学意义。在大体病理学检查中,发现残余肿瘤组的标本由消融中心向外共包括4种组织,即A坏死区,B炎反应及纤维带,C肿瘤残余带,和D癌旁肝组织,无肿瘤残留组则无C带。有肿瘤残留组则在炎性反应带和癌旁组织之间存在肿瘤细胞。
     1天组和1月组中残余肿瘤与炎性反应带间在平扫和三期增强CT值比较中均无统计学差异,而在3月组中CT平扫、动脉期、门静脉期CT值比较中肿瘤与炎症之间均有显著性差异(P<0.01)。在6月和1年组中肿瘤与瘤旁肝组织的CT扫描各期CT值对比中均有显著差异,其中动脉期和门静脉期P<0.01。在灌注扫描中,残存肿瘤与炎性反应带比较,1天、1月和3月组中参数血流量(BF)、血容量(BV)和肝动脉指数(HAF)在各时间点均有显著性统计学差异,且除3月组中BV值差异为P<0.05外,其余均为P<0.01;在6月组和1年组的肿瘤与瘤周正常肝灌注参数值间的比较中,BF、PS和HAP在两个时间点均表现出明显的统计学差异(P<0.01),BV在1年组中出现统计学差异。
     结论1.兔肝VX2肿瘤射频消融后残余肿瘤模型制作简单可行,成功率高。
     2.射频消融后病理学研究:RFA后病灶周围炎性反应带可能是CT强化带形成的病理学基础,炎细胞反应在3天达到高峰,随后逐渐减小,14天时多为纤维组织替代。
     3.常规CT动态增强扫描很难在RFA后1、3天正确鉴别残余肿瘤和炎性反应带,7、14天的CT增强检查可鉴别二者。
     4.原发性肝癌RFA治疗后早期阶段会出现病灶旁的炎性反应带,并在3个月内消失。RFA治疗后早期炎性反应带的CT增强程度与部分残余肿瘤相似。
     5.动态增强CT三期扫描能够鉴别RFA后3月组中的肿瘤残余/局部再发、肝内远处再发与炎性反应带,6月组和1年组的炎性反应带消失,CT增强检查能有效地鉴别肿瘤与瘤旁肝组织,从而在上述3个时间点能够满足临床诊断需要。
     6.CT灌注检查的BF、HAF不仅能够在6月和1年时间点上鉴别再发肿瘤与瘤旁肝组织,而且其BF、BV、HAF能够在1天、1月和3月时间点上鉴别残留肿瘤与炎症,很好地弥补了增强CT在RFA后早期的鉴别盲点。
     7.根据本研究病例组中肿瘤残余/局部复发和肝内远处再发出现的时间点和例数,提出肝癌射频消融术后CT检查的扫描方案。
Objective:The purpose was to observe the findings of hepatic VX2 tumor in rabbitsafter radiofrequency ablation(RFA)using both unenhanced,contrast enhancedmulti-detector CT and CT perfusion.To analyse the CT attenuation values onpre-enhanced and tri-phase contrast-enhanced examination and different parametervaluesof CT perfusion among the different days after RFA therapy,to compare thedifferences between remnant tumor and inflammatory reaction after RFA therapy.Todiscuss the value of both contrast enhanced CT and perfusion CT in differentiatigremnant tumor from inflammatory reaction.The purpose was to observe the findingsof HCC after RFA using both unenhanced,triphase contrast enhanced MDCT andCT perfusion.To analyse the CT attenuation values on pre-enhanced,tri-phasecontrast-enhanced examination and different parameter values of CT perfusion amongthe different period after RFA therapy,to compare the differences between localtumor progression (LTP),intrahepatic distant recurrence (IDR)and inflammatoryreaction after RFA therapy.To discuss the value of both contrast enhanced CT andperfusion CT in differentiatig LTP,IDR from inflammatory reaction.
     Materials and Methods:Twenty-four rabbits with hepatic VX2 tumor were assignedinto four groups,6 rabbits each group.In each group,three rabbits were establishedthe remnant tumor model,the others three rabbits were no remnant tumor after RFAtherapy.Each group were evaluated by contrast enhanced CT and perfusion CTduring the course of ld,3d,7d,14d after RFA,respectively.After imaging evaluation,they will be killed and observed in pathology.To observe the findings of contrastenhanced CT and perfusion CT,and register the CT attenuation value and perfusionparameters value,acquire the time density curve and artifact color images of differentperfusion parameters such as BF,BV,MTT,PS and HAF.To compare the differencesof the CT attenuation value and perfusion parameters value between remnant tumorand inflammatory reaction after RFA therapy among the 4 groups,respectively.Todefine which phases of contrast enhanced CT and parameters of perfusion CT candifferentiate remnant tumor from inflammatory reaction effectively through statisticalanalysis.
     We studied 36 patients with 45 HCCs who were treated with percutaneous RFablation.Triphase contrast enhanced CT and perfusion CT were performed at the timeof lday,1 month,3 month,6month and 1 year after RFA therapy.There were 21,22,16,16,23 HCCs that were examined by both contrast enhanced CT and perfusionCT at 5 periods (that mentioned above)after RFA therapy,respectively.Among them,2,3,8,5,6 LTPs,IDRs were found at the 5 periods,respectively.There were 19,14,3 HCCs which had surrounding inflammatory reaction at the time of 1d,1m,3m,respectively.To compare the differences between LTP,IDR and inflammatoryreaction (hepatic tissure around RFA focuse at time of 6m and 1 y)on both the CTattenuation value of unenhanced,contrast enhanced CT and the perfusion parametersof perfusion CT.after RFA therapy.To discuss the value of the two methods of CTscan in differentiatig LTP,IDR and inflammatory reaction (hepatic tissure aroundRFA focuse).
     Results:There had no statistical differences between remnant tumor andinflammatory reaction on every phase of unenhanced and tri-phase contrast enhancedCT in the group of 1d and 3d after RFA therapy.They,however,had significantdifference on the arterial and portal venous phase in the group of 7d,and on thearterial phase in the group of 14d.There had significant difference between remnanttumor and inflammatory reaction on the perfusion parameter of BF in all the groups,and they had significant difference on the parameter of BV and HAF in all the groupsbut 7d group.Considered all the data of four groups,the perfusion parameter of BF,BV,HAF had significant difference in differentiating remnant tumor frominflammatory reaction through ROC analysis.There were four types of tissue can beseen on the pathological sample,from inner portion to outer portion were necrosisarea,inflammatory reaction and fibrous zone,remnant tumor and hepatic tissurewhich surrounding the RFA focus,there was no remnant tumor zone in the group ofablated completely.RFA necrosis area,inflammatory reaction area (transform tofibrous tissue after 7 days)and the area of hepatocellular edema can be seen onmicroscopy examination in the group of remnant tumor,and tumor cells can be seenbetween the area of inflammatory reaction and hepatocellular edema in the group ofablated completely.
     There had no statistical differences between LTP,IDR and inflammatoryreaction on every phase of unenhanced and tri-phase contrast enhanced CT at time ofld and lm.after RFA therapy.However,there had significant differences on theunenhanced CT scan and the phase of arterial and portal venous at time of 3m afterRFA therapy(P<0.01).There had significant differences between LTP,IDR andhepatic tissue around RFA focuse on every phase of unenhanced and tri-phasecontrast enhanced CT at time of 6m and 1 y after RFA therapy.There had significantdifferences between LTP,IDR and inflammatory reaction on the perfusion parametersof BF,BV,HAF at time of ld,lm,3m after RFA therapy,however,they had nosignificant differences on the perfusion parameters of MTT and PS at all time afterRFA therapy,except for the PS at time of 3m(P<0.05).There had significantdifferences between LTP,IDR and hepatic tissue around RFA focuse on the perfusionparameters of BF,PS and HAF at time of 6m and 1y,BV at 1y after RFA therapy.Considered all the data of earlier three groups,the perfusion parameter of BF,BV,HAF had significant difference in differentiating LTP,IDR from inflammatoryreaction through ROC analysis,the value of Az were 0.955,0.891,0.929,respectively.
     Conclusion:1.The remnant hepatic tumor of VX2 rabbits after RFA were alike thehumans'HCC residue and local recurrence,it can be copied easily and successfully.
     2.Ring like enhancement of RFA focuse on the contrast enhanced CTexamination may be based on the pathological change of inflammatory reactionaround it.Inflammatory reaction arrived its' peak at the day 3,then subsidedeventually,it can be substituted by fibrous tissue at day 14.
     3.It was hard to differentiate remnant tumor from inflammatory reaction atday 1 and day 3 using only triphase contrast enhanced CT examnination,however,itcan be done at day 7 and day 14.
     4.Inflammatory reaction may be appeared around the HCC focuse at earlierphase after RFA therapy,and subsided eventually at the subsequent 3 months.Theyhad similar enhancement in contrast enhanced CT scan between LTP,IDR andinflammatory reaction among part of cases.
     5.Tri-phase contrast enhanced CT scan could differentiate LTP,IDR from inflammatory reaction at time of 3m,and it could also differentiate between LTP,IDRand hepatic tissue around RFA focuse at time of 6m and 1 y after RFA therapy,that is,tri-phase contrast enhanced CT scan could meet the need of clinical diagnosis at timeof 3m,6m and ly after RFA therapy.Tri-phase contrast enhanced CT scan could notdifferentiate LTP,IDR from inflammatory reaction at time of ld and lm after RFAtherapy,because of their similar enhancement,it could differentiate throughmorphological change.
     6.Perfusion CT could differentiate LTP,IDR from hepatic tissue around RFAfocuse not noly on the parameters of BF,HAF at time of 6m and l y,but also BF,BV,HAF at time of ld,lm and 3m.Perfusion CT could make up the blind spot ofdifferentiate diagnosis that contrast enhanced CT could not do at the earlier phaseafter RFA therapy.
     7.We suggested that a new follow-up CT scan protocol after RFA therapyshould be performed at time of 1,3,6,9 and 12 month after RFA therapy.
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    2.Liver Cancer Study Group Of Japan.Primary liver cancer in Japan: clinicopathologic and results of surgical treatment.Ann Surg 1990;211:277-84
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