胃肠间质瘤-229.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,GIST,1,定义,2,临床特点,和,检查手段,3,病理学,和,影像学,表现,4,药物治疗,5,预后,定义,主要发生于消化管道含有梭形细胞、非普通型上皮样细胞或含有两种细胞并显示,CD117,活性的间叶细胞瘤。,胃肠道间叶源性肿瘤（,gastrointestinal mesenchymal tumor,GIMT,）与,GIST,概念与所含肿瘤范围不同，,GIMT,中约,73%,为,GIST,，其他,GIMT,有平滑肌瘤、平滑肌肉瘤、脂肪瘤、神经鞘瘤和胃肠道自主神经肿瘤（,gastrointestinal autonomic nerve tumor,GANT,）等。,History,before 1983:regarded as,leiomyomas,leiomyosarcomas,or,leiomyoblastomas,schwannomas,1983:Mazur and Clark,differ,GISTs,from smooth muscle,(,immunostaining,and electron microscopy),1998:,Kindblom,morphological and,immunophenotypic,similarities to ICC,1998:,Hirota,gain-of-function mutations in the,protooncogene,c-kit in,GISTs,2003:,Heinrich,mutations in,PDGFRa,(class III,tyrosin,kinase,),命名由来,临床特点,平均年龄,54.5,岁,40,岁以前少见。,无特异性临床症状和体征,临床表现和消化道其它肿瘤类似,决定于肿瘤的大小,发生部位,肿物与胃肠的关系,及肿瘤系良性、潜在恶性及恶性有关。,肿瘤直径,2 cm,者,常无症状,常在癌症普查、体检和其它手术时无意中发现。,最常见的症状是中上腹部不适和腹部肿块（,50%,70%,）,便血（,20%,50%,）,小肠,GISTs,可表现为疼痛,便血或肠梗阻等。,6070%,stomach,2030%,Small int.,5%,5,转移率高达,15%,30%,坏死率极高：,5cm,以上坏死率,100%,转移至肝多见，且一般囊性变，故需和囊肿鉴别,检查手段,X,线吞钡或灌肠,B,超及内镜超声,CT,或,MRI,内镜,影像学表现,X,线吞钡造影特征：一般腔内生长表现为充 盈缺损，当发生坏死时，钡剂与空气进入时可以形成起液面。肠道钡餐检查主要为肠管受压推移改变,肠曲增宽。,小 肠,CT,增强：可以了解血供关系。,CD34,组织学特点,CD117,CD34,SMA,S-100,Desmin,GIST,7494%,60%-70%,30%-40%,5%,1%-2%,leimyoma,10%-15%,schwannoma,Fletcher.(2002),病理鉴别诊断,When CD117 is negative,the diagnosis of GIST can still be made if the histology is typical and S100,SMA and,desmin,staining are negative,CD117,1,C-KIT,蛋白产物,GIST,的高特异性的标记物,GIST,表达,CD117,阳性者达到,95%,以上，平滑肌瘤、平滑肌肉瘤、神经鞘瘤,CD117,阴性，以此为鉴别依据。,Table 2.Risk of Aggressive Behavior in,GISTs,(Fletcher et al,2002),Size(largest dimension),Mitotic Count,very low risk,2 cm,5/50 HPF,low risk,2-5 cm,5/50 HPF,intermediate risk,5 cm,6-10/50 HPF,5-10 cm,5 cm,5/50 HPF,10 cm,any mitotic rate,预后,生物学行为的判定,影响,GISTs,生物学行为的因素有,:,有无邻近脏器的侵犯及远处转移,有无粘膜侵犯,核分裂相数目,瘤体大小,肿瘤细胞密集程度,细胞异型性,有无出血坏死,细胞增殖指数,以及发生部位等,47%,的恶性间质瘤可有转移，转移部位多位肝脏，继为腹膜、肺、骨、淋巴结等,恶性标准,临床上还可根据局部浸润、转移、复发、肿瘤部位判定。,如：肯定恶性指标包括：转移（组织学证实）；侵润至邻近器官；原发的大肠的间质瘤有基层侵润。,潜在恶性指标：,肿瘤长径在胃部,5.5cm,，在肠道,4cm,；核分裂相在胃部,5/50HPE,（高倍视野），在肠道,1/50HPF,；肿瘤坏死；核异形性明显；细胞丰富；小上皮细胞呈细胞巢或腺泡状排列。,Cause,Common,mesenchymal,precursor cell,ICCs,Smooth muscle cell,GIST cell,Cause,KIT,Gain-of-function mutations of the c-,kit,proto-oncogene.,This gene encodes a,transmembrane,receptor for a growth factor,scf,(stem cell factor).,The,c-kit,/CD117 receptor is expressed on,ICCs,and a large number of other cells,mainly bone marrow cells,mast cells,melanocytes,and several others.,PDGFRA,Cause,格列卫,蛋白酪氨酸激酶,BCR-ABL,蛋白 阿利克斯,梅塔博士,(Dr.Alex Matter)1993,年小分子化合物抑制激酶家族中的蛋白激酶,C(Protein Kinase C)STI571,2001,年,5,月,10,日批准通过它上市，总共审批时间,2,个半月 治疗,Chronic Myeloid Leukemia,，,CML,GLEEVEC,抑制 两种激酶,PDGF-R(platelet-derived growth factor receptor),和,C-Kit,。,2002,年,FDA GLEEVEC,对,GIST,的治疗作用。,C-Kit,还涉及到小细胞肺癌,(Small Cell Lung Cancer),的形成,Treatment,Surgery-,Surgery is the first step in treatingGIST and is often curative,.,Imatinib,(,Gleevec,),-,Imatinib,(,Gleevec,)is FDA-approved for,unresectable,and metastatic GIST.,Sunitinib,(,Sutent,),-,Sunitinib,(,Sutent,)is FDA-approved for GIST resistant to,imatinib/Gleevec,and for patients who are intolerant of,imatinib/Gleevec,.,Hepatic artery,embolization,-,Embolization,is a surgical procedure for liver metastases of GIST.,Radiofrequency ablation,-RFA is a surgical procedure for liver metastases of GIST.,GIST,的组织学证据,不能手术：,伊马替尼 400 mg/日,疾病稳定或 有效,继续,伊马替尼 400 mg/日,疾病进展,全身进展,原发能够手术：,切除,不能完全切除：,伊马替尼,400,mg/,日,完全切除：,伊马替尼辅助治疗（正在临床试验阶段）,增加剂量至,800 mg/日,舒尼替尼,局部进展,增加剂量至,800,mg/,日,+,局部治疗,(,手术，射频消融，,激光热疗,),进入临床试验：,伊马替尼,6,00 mg/,日,+RAD001,进入临床试验：,Nilotinib,vs.,最佳支持治疗,转移性：,伊马替尼,400,mg/,日,腹部肿瘤的证据，,GIST,鉴别诊断,分期,进行活检，如制定治疗方案需要,治疗后可切除：切除,预后,GISTs,临床行为难测,如,1,至,2,大小肿瘤也有发生转移者。胃间质瘤,5,转移率高达,15%,30%;,肠间质瘤,5,转移率可达,50%,。,GISTs,的,5,年生存率,50%,60%,10,年生存率,35%,43%,。高度恶性间质瘤,5,年死亡率,100%;,低度恶性间质瘤,5,年生存率大于,75%,。恶性,GISTs,当发生在胃时比小肠好。,10,年生存率,:,胃,95%,小肠,17%,Consensus meeting for the management of gastrointestinal,stromal,tumors.,Report of the GIST Consensus Conference of 20-21 March 2004;Ann,Oncol,.2005 Apr;16(4):566-78.,Corless,CL,Fletcher JA,Heinrich MC.,Biology of gastrointestinal,stromal,tumors.,J,Clin,Oncol,.2004 Sep 15;22(18):3813-25.,DeMatteo,RP(editor).,Multidisciplinary Management of Primary and Metastatic GIST,Highlights from an educational activity offered during the Society of Surgical Oncologys 2008 Annual Cancer Symposium,March 13-16,2008 in Chicago,Illinois.,Demetri,GD.Gastrointestinal,stromal,tumors.Chapter 29 in VT,DeVita,Jr.,S Hellman,and SA Rosenberg(editors),Cancer:Principles and Practice of Oncology,7th edition.Philadelphia:Lippincott Williams&Wilkins,2005.,Reference,