【作者】 陈亮；

【导师】 丁晓毅；

【作者基本信息】 上海交通大学 ， 影像医学与核医学， 2015， 博士

【摘要】 伴有软组织肿块的骨巨细胞瘤经局部刮除术后复发的深入分析目的:通过回顾分析伴有软组织肿块的骨巨细胞瘤(GCTB)患者经局部刮除术后复发率,寻找能预测与局部刮除术后复发有关的软组织肿块核磁共振影像特征。材料和方法:回顾分析48例伴有软组织肿块骨巨细胞瘤患者。所有患者均行局部刮除手术。所有病例按软组织肿块的MR影像及病理特征(如软组织肿块的大小、数量、边界是否完整、周围组织受累、软组织肿块MR信号强度、增强MR信号特征和Jaffe分级)分组。各组局部刮除术后复发率差异比较采用卡方检验(chi-square test)或卡方值校正的连续性检验(chi-square test andχ2 value correction for continuity)。与局部刮除术后复发有关的软组织肿块MR影像特征的危险因素评估采用多因素回归分析检验(multivariate logistic regression analysis)。p<0.05认为有统计学差异。结果:在MR图像上,当骨巨细胞瘤伴有较大软组织肿块、多发软组织肿块或软组织肿块边界不完整时,采用局部刮除手术后复发率较高,结果具有统计学差异(p<0.05)。在软组织肿块周围组织受累、Jaffe分级组中,其局部刮除术后复发率之间没有统计学差异(p>0.05)。软组织肿块的大小、数量和边界是否完整是骨巨细胞瘤病灶经刮除术后复发的独立危险因素(p<0.05)。结论:当GCTB伴有较大软组织肿块、多发软组织肿块或软组织肿块边界不完整时,采用局部刮除术后复发率较高。临床遇到具有此类软组织肿块MR影像特征的GCTB患者,在选择外科手术治疗方案时,其局部刮除术后较高的复发率需要充分考虑。三期对比增强核磁共振检查在预测骨巨细胞瘤恶变的价值目的:通过对骨巨细胞瘤(GCTB)、复发良性骨巨细胞瘤(RBGCTB)、继发恶性骨巨细胞瘤(SMGCTB)三期动态对比增强MR图像上时间-信号强度曲线特征的比较,寻找能预测骨巨细胞瘤恶变的新线索。材料与方法:回顾分析21例经手术病理确诊为骨巨细胞瘤的患者。所有病例均在术后复发。其中,9例复发病例病理证实为SMGCTB,12例复发病例术后病理证实为RBGCTB。病例分为四组:A组:术前GCTB(n=9);B组:术后SMGCTB(n=9);C组:术前GCTB(n=12);D组:术后RBGCTB(n=12)。病灶在三期动态对比增强MR图像上增强指数(EI)计算公式:EI(t)=[S(t)-S(0)]/S(0),其中S(0)是病灶T1加权平扫图像上的平均信号强度,S(t)是病灶在动态对比增强MR图像不同期相的信号强度(t分别为注射造影剂后30,60和180秒)。每组病灶在动态对比增强MR检查不同期相的增强指数差异检验采用单因素方差分析(One-Way ANOVA analysis)。在三期动态对比增强MR图像上,病灶的时间-信号强度增强曲线的上升和下降斜率值比较采用同样方法。p<0.05认为有统计学差异。结果:在三期动态对比增强MR图像上,SMGCTB的时间-信号强度曲线的特点是早期造影剂快速流入和延迟期造影剂快速廓清。GCTB和RBGCTB的时间-信号强度曲线的特点是早期造影剂快速流入和延迟期造影剂缓慢廓清。在三期动态对比增强MR图像第一期相中,各组间的增强指数没有统计学差异(p>0.05)。在三期动态对比增强MR图像的第二期和第三期中,各组间的增强指数存在统计学差异(p<0.05)。B组(SMGCTB)增强指数较其他三组低。时间-信号强度曲线的上升斜率值在各组间无统计学差(p>0.05)。时间-信号强度曲线下降斜率值在各组间存在统计学差异(p<0.05)。B组(SMGCTB)下降斜率的平均绝对值较其他组高(p<0.05)。结论:三期动态对比增强MR图像的时间-信号强度增强曲线特征可为预测骨巨细胞瘤术后恶变提供有价值的线索。动态对比增强MR检查是GCTB患者术前和术后重要的影像随访资料。骨巨细胞瘤边缘组织和中央组织基质金属蛋白酶-9表达与MRI影像意义的初步研究目的:通过比较骨巨细胞瘤中央组织和边缘组织MMP-9表达水平并对照MR图像特征,以期发现肿瘤内部不同部位MMP-9表达差异及其与MRI影像学意义,为肿瘤内部不同部位肿瘤细胞采用不同靶点治疗提供参考依据。材料与方法:收集经手术后病理证实为骨巨细胞瘤并行局部瘤段切除手术患者新鲜标本或石蜡固定标本17例。每例标本在病灶中央和边缘各取材4处。其中4例标本行半定量RT-PCR、Western blot蛋白免疫印迹法测定标本MMP-9 m RNA和MMP-9蛋白的表达。所有标本均行连续切片HE染色和MMP-9免疫组化染色。同时,对GCTB边缘组织和中央组织MMP-9免疫组化染色程度与MR图像特征关系进行评估。计量资料采用均数±标准误(mean±standard error)表示。两组资料样本均数差异的检验采用Student’s t-tests检验。多组资料样本均数检验采用方差分析检验(one-way analysis of variance ANOVA)或卡方值校正的连续性检验(chi-square test orχ2 value correction for continuity)。各组间样本均数两两差异检验采用(Dunnett’s post-test)检验。分类变量样本均数差异比较使用Chi-square test检验,p<0.05被认为有统计学差异。结果:在免疫组化染色病例中,GCTB边缘组织MMP-9染色程度大于2级(++)时,其阳性率为77.94%,中央组织MMP-9染色程度大于2级(++)时,其阳性率为29.41%。两者间具有统计学差异,p<0.05。RT-PCR实验结果显示GCTB边缘组织、中央组织和周围正常组织中MMP-9 m RNA相对表达水平分别为0.88±0.07、0.35±0.04和0.12±0.03,各组间有统计学差异,p<0.05。Western blot实验结果显示MMP-9蛋白在GCTB边缘组织、中央组织和周围正常组织相对表达水平分别为0.92±0.04,0.42±0.06和0.13±0.02,各组间有统计学差异,p<0.05。GCTB边缘组织MMP-9 m RNA和蛋白的相对表达水平较中央组织和周围正常组织高。在MR图像表现为局部骨质破坏并软组织肿块形成的病例中,边缘组织MMP-9免疫组化染色程度为2-3级的样本数大于染色程度为0-1级的样本数,结果有统计学差异,p<0.05。中央组织MMP-9染色程度的差异与MR图像表现为局部骨质破坏及软组织肿块形成之间无统计学差异,p>0.05。GCTB边缘组织和中央组织MMP-9染色程度差异与MR图像表现为邻近组织受累、MRI信号特征、MRI增强特征之间无统计学差异,p>0.05。结论:骨巨细胞瘤边缘组织MMP-9表达高于中央组织。骨巨细胞瘤边缘组织MMP-9的高表达可能与局部骨质破坏并软组织肿块有相关。如果以MMP-9作为骨巨细胞瘤生物学标记物或潜在治疗靶点时,需考虑其在肿瘤内部不同部位的差异表达。更多还原

【Abstract】 Deep Analysis of local recurrence of giant cell tumor of bone with soft tissue extension after intralesional curettageObjective: Our purpose was to assess local recurrent rate of giant cell tumor of bone(GCTB) with soft tissue extension to spot new clues for the prediction of which characteristic features of the soft tissue extension best indicated the recurrence of GCTB after intralesional curettage.Materials and methods: 48 cases of GCTB with soft tissue extension after intralesional curettage were recruited. Patients were divided into two groups based on various objective features of the soft tissue extension, such as size, number, margin, adjacent tissues evolvement, signal intensity characteristics, static enhancement and Jaffe’s grade. Difference of local recurrence rate in each group was compared by chi-square test and χ2 value correction for continuity. Risk factors were assessed by multivariate logistic regression analysis.Results: Local recurrence rate had significant difference in groups of extended soft tissue’s size, number and margin(p <0.05). There was no significant statistical difference in groups of adjacent tissues evolvement and Jaffe’s grade(p >0.05). Soft tissue’s size, number and margin were independent risk factors of local recurrence of GCTB with soft tissue extension after intralesional curettage(p<0.05).Conclusions: The local recurrence rate of GCTB with soft tissue extension treated by intralesional curettage would be higher if the extended soft tissue is large, multiple and without integrated bone-envelope around. When meeting such conditions, we advocate the higher recurrence rate should be taken into full consideration for the choice of appropriate surgical procedures.Triple-Phase Dynamic MRI: A New Clue to Predict Malignant Transformation of Giant Cell Tumor of BoneObjective: Our purpose was to compare characteristics of time-intensity curve on triple-phase dynamic contrast-enhanced MRI among groups of giant cell tumor of bone(GCTB), recurrent benign giant cell tumor of bone(RBGCTB), and secondary malignant giant cell tumor of bone(SMGCTB) to find clues to predict the malignant transformation of GCTB.Subjects and methods: 9 cases of SMGCTB, 12 cases of RBGCTB were involved in our study. Cases were divided into four groups: group A, GCTB(n=9); group B, SMGCTB(n=9); group C, GCTB(n=12); group D, RBGCTB(n=12). Enhancement index(EI) of lesion on DCEMRI was calculated using formula: EI(t)=[S(t)-S(0)]/S(0), where S(0) was signal intensity of lesion on non-contrast-enhanced T1-weighted images and S(t) was signal intensity of lesion on DCEMRI(t=30,60,180 sec).Enhancement index of each group in each phase was compared using One-Way ANOVA analysis. Slope values of time-intensity curve were compared by the same way.Results: Time-intensity curve of SMGCTB was characterized by a steep upward slope followed by an early and rapid washout phase. Time-intensity curve of GCTB and RBGCTB was characterized by a steep slope followed by a relatively slow washout phase. No significant difference of enhancement index was found in the first phase(p>0.05). There was significant difference in the second and the third phase(p<0.05). Enhancement index of group B(SMGCTB) was smaller. There was difference of descending slope value(p<0.05) and no difference of rise slope value(p>0.05).Conclusions: Dynamic contrast-enhanced MRI appears a helpful method to find new clue to predict the malignant transformation of GCTB. We suggest patients of GCTB should take DCEMRI examination before and after operation and DCEMRI should be important data of clinical followed-up.Expression and MRI Significance of Matrix Metalloproteinase-9 in Peripheral tissue and Central tissue of GCTBObjective: Our purpose was to compare MMP-9 expression in peripheral tissue, central tissue in giant cell tumor of bone(GCTB) and MMP-9 protein expression with MRI parameters to find evidences of multiple therapeutic targets of GCTB.Subjects and methods: 17 cases of GCTB were involved in our study. 4 specimens in peripheral tissue, central tissue and normal tissue in each GCTB case were chosen respectively. 4 cases were examined by RT-PCR and Western-blot to test MMP-9 m RNA and protein expression. All cases were examined by immunohistochemical staining and HE staining. The correlations of MMP-9 immunohistochemical staining grade and MRI parameters were also evaluated. Data were expressed as mean ± standard error. Student’s t-tests were used to compare two sets of data. The relative expression of MMP-9 m RNA and protein were compared using One-Way ANOVA analysis with Dunnett’s posttest for comparisons of more than two data sets. Non-parametric statistics(chi-square test or χ2 value correction for continuity) were applied to data with abnormal distribution and p values of <0.05 were considered statistically significant.Results: MMP-9 immunohistochemical staining grade which were over 2 grade(++) in peripheral tissue(77.94%) was higher than that in central tissue(29.41%), p<0.05. MMP-9 m RNA relative expression levels in peripheral tissue, central tissue and normal tissue were 0.88±0.07, 0.35±0.04 and0.12±0.03 respectively. MMP-9 protein relative expression levels in peripheral tissue, central tissue and normal tissue were 0.92±0.04, 0.42±0.06 and 0.13±0.02 respectively. Higher MMP-9m RNA and protein expression levels were detected in peripheral tissue. p<0.05. On MRI which showed local bone destruction with soft tissue extension, the numbers of MMP-9 immunohistochemical staining grade shown as 2-3 grade in peripheral tissue were more than that shown as 1-2 grade. No significant difference between cases which showed as local bone destruction with soft tissue extension on MRI and MMP-9 immunohistochemical staining grade in central tissue was found. There was no significant difference was found between MMP-9 immunohistochemical staining grade in peripheral tissue, central tissue of GCTB and other MRI characteristics.Conclusions: The MMP-9 relative expression in peripheral tissue was higher than that in central tissue of GCTB. The over expression of MMP-9 in peripheral tissue of GCTB was correlated to local bone destruction with soft tissue extension on MRI. If we took MMP-9 as a biomarker or potential therapeutic target of GCTB, the different expression level in different part of GCTB should be taken into full consideration.更多还原