胃肠道间质瘤伊马替尼术前治疗进展

目的 探讨伊马替尼术前治疗胃肠道间质瘤（gastrointestinal stromal tumor,GIST）的作用。 方法 采用文献复习的方法,对研究伊马替尼术前治疗GIST的文献加以综述。 结果 伊马替尼术前治疗是进展期GIST的有效治疗手段,能显著提高患者的手术切除率,延长总体生存时间。 结论 术前伊马替尼治疗转移性或局部进展期GIST疗效较好,应参考GIST基因分型结果个体化术前给药,值得进一步深入临床研究。     

胃肠道间质瘤的诊治现状与进展

目的总结胃肠道间质瘤（GIST）的发病机制及流行病学特点,探讨其诊断及治疗并分析其预后。方法复习与GIST的发病机制、流行病学、诊断、治疗及预后方面有关的文献并对其进行综述。结果 GIST为非上皮源性肿瘤,起源于Cajal间叶细胞,是消化道最常见的间叶性肿瘤,约占消化道肿瘤的1%～3%,中位发病年龄为40～60岁,胃为最好发部位。目前认为,GIST的发病机制与原癌基因c-kit或血小板源性生长因子受体α（PDGFRα）基因突变有密切关系,但PDGFRα和c-kit基因突变不会同时出现在同一患者中。GIST的临床表现缺乏特异性,临床诊断主要依靠内镜及影像学技术,最终确诊依靠病理学检查。目前对GIST的治疗以手术与分子靶向药物治疗为主,其预后与肿瘤危险度分级及治疗干预密切相关。结论 GIST是具有恶性潜能的肿瘤,其危险度分级是指导临床治疗及预后评估的重要指标,GIST的预防、诊断、治疗及复发的预防有待进一步研究。     

胃肠道间质瘤的分子靶向治疗

胃肠道间质瘤（GIST）主要由突变的c-kit或血小板源性生长因子受体α（PDGFRα）基因驱动.分子靶向药物伊马替尼（imatinib）的问世,成为了GIST患者分子靶向治疗里程碑式的进展.但伊马替尼根据GIST的基因型不同,而显示出不同活性,且KIT和PDGFRα突变状态和其突变外显子的类型与GIST对酪氨酸激酶抑制剂的临床反应相关.因此需要对不同突变类型的GIST患者进行突变类型检测,并分别选择相应的酪氨酸激酶抑制剂治疗.尽管酪氨酸激酶抑制剂在很大程度上改善了GIST患者的生存状态,但大约有20%的GIST原发对imatinib耐药,且多数患者在酪氨酸酶抑制剂治疗2年内形成继发耐药,因此将来GIST的治疗可能更加倾向于多种药物、多类药物,靶向多层面的胞内信号转导通路的联合使用.     

基因突变检测在胃肠间质瘤诊断和治疗中的应用及其价值

c-kit和PDGFRA基因突变是胃肠间质瘤（GIST）最重要的分子特征。对这两个基因突变的检测对于诊断KIT阴性GIST具有重要意义,同时还可以用于预测酪氨酸激酶受体抑制剂的治疗效果。此外,近年来更多的研究关注于把基因突变状态作为判断GIST预后因子的可行性。     

胃肠道间质瘤的分子靶向治疗

分子靶向药物的出现,改变了胃肠道间质瘤(GIST)的治疗模式.伊马替尼400 mg/d被推荐为转移性GIST的标准一线治疗方案.伊马替尼标准剂量治疗失败后,增加伊马替尼剂量或换用舒尼替尼治疗可进一步延长患者生存时间,同时新的分子靶向药物显示出了治疗GIST的潜在活性.GIST完整切除术后,伊马替尼辅助治疗可改善中高度复发风险患者的无复发生存率.伊马替尼术前治疗可提高手术切除率,但是否使患者生存获益尚未得到最终证实.c-kit和(或)血小板源性生长因子受体α(PDGFRα)基因突变可以预测伊马替尼与舒尼替尼的疗效,同时亦有助于辅助治疗获益人群的筛选.     

胃肠道间质瘤36例临床分析

目的总结胃肠道间质瘤(GIST)的临床特点、诊断与治疗方法。方法回顾性分析36例胃肠道间质瘤患者的临床和病理资料。结果36例GIST患者均行手术治疗,其中良性20例,交界性10例,恶性6例。30例患者获随访2~3年,其中2例死于肿瘤复发转移,1例术后28个月复发再行手术治疗。结论GIST术前诊断较困难,确诊依赖于病理学检查。手术是主要治疗方法,分子靶向治疗具有辅助意义。     

胃肠间质瘤病理诊断和分子检测

胃肠间质瘤（GIST）的病理诊断和分子检测对临床治疗和预后判断非常重要。从事GIST诊治的临床医生和病理医生均应熟悉GIST的临床病理学特点和分子检测相关内容,并了解一些容易被误诊为GIST的肿瘤类型,避免误诊和误治,使GIST病人从最大程度上获益。     

基因芯片在乳腺癌基因分子分型及个体化治疗方面的应用

乳腺癌是严重威胁女性健康的恶性肿瘤之一,发病率高,临床上主要借助影像学、针刺细胞学、病理学等方法进行乳腺癌的早期诊断和治疗,但乳腺癌的基因异质性导致相同病理分期的患者对临床治疗有不同的反应且预后不同.确定一种能够准确反映乳腺癌临床分型、预测疗效及预后的分子和基因分型,对于指导乳腺癌个体化治疗和改善乳腺癌患者的预后具有重要意义.本文对基因芯片在乳腺癌分子、基因分型方面的研究及其在个体化诊疗方面的应用作一综述.     

分子靶向治疗胃肠间质瘤的进展

胃肠间质瘤(gastrointestinal stromal tumor,GIST)是最常见的胃肠道间叶源性肿瘤.其发病率约占消化道肿瘤的1%,年发病率为15/100万,发病中位年龄约为60岁.约有20%～30%的患者是GIST高度侵袭危险人群[1].由于GIST对常规放疗及化疗均极不敏感,既往手术是其主要且惟一有效的治疗手段,然而高危GIST患者极易复发.以前对于GIST.无法切除或转移复发患者缺乏良好对策,近年来随着GIST.发病机制的进一步阐明,分子靶向治疗药物伊马替尼和舒尼替尼在临床应用中取得了令人瞩目的疗效,现将其研究进展综述如下.     

胃肠间质瘤靶向治疗耐药的分子机制及治疗策略

胃肠间质瘤（GIST）是胃肠道最常见的间叶源性肿瘤。功能获得性突变所致的c-kit或PDGFRA受体酪氨酸激酶异常活化是大多数GIST发病的关键因素。伊马替尼及舒尼替尼等分子靶向药物可特异性抑制酪氨酸激酶受体活化．其作为治疗晚期GIST及高危GIST术后辅助治疗的一线治疗地位已经得到广泛认可,并成为了实体肿瘤分子靶向治疗的经典模型。但同时以上药物的耐药问题一直是临床治疗中的棘手难题和研究热点。许多因素与发生伊马替尼或舒尼替尼耐药有关,其中．KIT／PDGFRA的基因突变是决定耐药与否的主要原因。此外,可能还涉及基因扩增、杂合性丢失和近膜热点区域之外的旁路激活及药物血浆浓度等原因。对于出现肿瘤耐药的患者,应根据不同的耐药原因,采取相应的个体化治疗策略,以期提高治疗效果,改善患者生活质量。     

胃肠间质瘤靶向治疗耐药机制及治疗策略新进展

胃肠间质瘤是胃肠道最常见的间叶组织来源肿瘤．获功能性突变的KIT和PDGFRA受体酪氨酸激酶异常活化是多数胃肠间质瘤发病的关键因素。伊马替尼和舒尼替尼等分子靶向药物是晚期或不可切除胃肠间质瘤患者疗效确切的一线及二线治疗选择,但伊马替尼耐药是临床中的棘手问题及研究热点。本文对伊马替尼耐药的分子机制和耐药后治疗策略的选择以及靶向治疗的新进展进行讨论。未来分子生物学指导下的个体化治疗有望进一步提高胃肠间质瘤疗效,改善患者生存。     

Combined surgical and molecular therapy: the gastrointestinal stromal tumor model

OBJECTIVE: This review describes the pathologic and epidemiologic features of gastrointestinal stromal tumor (GIST) as well as the contemporary management of this tumor. The integration of surgery and treatment with targeted molecular agents in the treatment of GIST is highlighted. SUMMARY BACKGROUND DATA: GIST is the most common mesenchymal tumor of the gastrointestinal tract. Its cellular origin from the interstitial cell of Cajal and distinctness from smooth muscles tumors were only recently appreciated. The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST. METHODS: We conducted a review of the English literature on GIST. The pathology, epidemiology, diagnosis, and treatment of this tumor are summarized with particular emphasis on recent developments in the field. RESULTS: GIST is a rare tumor that usually arises from the stomach or small intestine. It is characterized by immunohistochemical staining for KIT. Treatment of primary localized tumors is surgical. The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. The treatment of unresectable, recurrent, or metastatic GIST is primarily imatinib treatment. The integration of surgery or ablative modalities is often employed, particularly when all disease is amenable to gross resection or destruction, or when GIST becomes resistant to imatinib. Newer tyrosine kinase inhibitors, such as sunitinib are the subject of ongoing investigation. CONCLUSIONS: The treatment paradigm for GIST has required the integration of surgery and molecular therapy and this will likely serve as a paradigm for the treatment of other solid tumors as targeted agents are developed.     

重视野生型胃肠间质瘤的诊断与治疗

胃肠间质瘤是胃肠道最常见的间叶源性肿瘤．c．kil基因或PDGFRA基因的功能获得性突变是其最重要的特征。有10％～15％的胃肠间质瘤不存在c—kit基因及PDGFRA基因的突变．称为野生型胃肠间质瘤。这一类胃肠问质瘤在分子机制及临床特征上与突变型胃肠间质瘤有湿著差异．且其本身存在高度异质性。临床医师在诊断与治疗野生型胃肠间质瘤时应当引起足够的重视。     

������θ���������ٴ�����

??Reoperation for recurrent gastrointestinal stromal tumors CAI Jian-qiang. Department of Abdominal Surgical Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
Abstract Surgical resection is still the primary curative treatment for gastrointestinal stromal tumor(GIST) patients. However, postoperative recurrence and metastasis of tumors are the major causes of treatment failure and patients death. Surgery is not the best choice for recurrent GIST. It is considerable to combine surgical and molecular therapy to increase the overall survival of GIST patients.     

Gastrointestinal stromal tumor surgery and adjuvant therapy

Gastrointestinal stromal tumors (GIST) are a unique class of mesenchymal tumors identified within the past decade. Intense molecular and genetic study has been used to characterize these tumors and develop treatment strategies. Although the mainstay of treatment remains surgical resection, therapy targeted at inhibiting tyrosine kinases has had dramatic results. Because of the rapid accumulation of information about the diagnosis and treatment of these tumors, the National Comprehensive Cancer Network convened a GIST task force to provide updated recommendations in 2010. As understanding of these tumors advances, rapid changes in recommendations will continue and should warrant regular updates in tumor management.     

复发性胃肠间质瘤再次手术

外科手术目前仍是胃肠间质瘤（GIST）病人获得根治的最佳手段,但术后复发转移是GIST病人治疗失败及死亡的主要原因。对于复发性GIST,外科治疗并不是最佳选择,应联合酪氨酸激酶抑制剂甲磺酸伊马替尼,结合病人的不同情况,个体化制定综合治疗方案,以提高病人总生存期。     

Laparoscopic approach of gastric gastrointestinal stromal tumors (GISTs): is it still a courageous choice? Report of two cases

Gastrointestinal stromal tumors (GISTs) are a well-defined clinicopathologic and molecular tumor entity, representing the most common gastrointestinal mesenchymal neoplasm. Differential diagnosis between GIST and other mesenchymal malignancies is crucial, given the successful management using targeted therapy in metastatic GIST. The mainstay of treatment remains surgery, complete tumor resection being the most important independent prognostic factor. Videolaparoscopic approach is still controversial for the high risk of tumor rupture or bleeding. Here we report 2 cases of GIST surgically resected using a videolaparoscopic approach and discuss the efficacy of this technique in selected patients.     

胃肠间质瘤免疫疗法及新策略的研究进展

胃肠道间质瘤（GIST）是源自Cajal间质细胞的软组织肿瘤,是胃肠道肉瘤的一种常见类型。靶向药物的发现大大提高了GIST的生存率,而伊马替尼作为靶向药物,已经成为GIST的一线治疗药物。然而,最近研究发现,大多数患者已经对伊马替尼产生了耐药性。最新的研究表明,免疫疗法,包括基于免疫检查点抑制剂和伊马替尼联合疗法、细胞因子、抗KIT抗体、双特异性单克隆抗体疗法和其他新型策略,对治疗胃肠道间质瘤也是有效的。在本综述中,将讨论免疫疗法和其他新策略在治疗胃肠道间质瘤中的作用。     

A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) occur primarily in the wall of the intestine and are characterized by activating mutations in the receptor tyrosine kinases genes KIT or PDGFRA. The diagnosis of GIST relies heavily on the demonstration of KIT/CD117 protein expression by immunohistochemistry. However, KIT expression is absent in approximately 4% to 15% of GIST and this can complicate the diagnosis of GIST in patients who may benefit from treatment with receptor tyrosine kinase inhibitors. We previously identified DOG1/TMEM16A as a novel marker for GIST using a conventional rabbit antipeptide antiserum and an in situ hybridization probe. Here, we describe 2 new monoclonal antibodies against DOG1 (DOG1.1 and DOG1.3) and compare their staining profiles with KIT and CD34 antibodies on 447 cases of GIST. These included 306 cases with known mutational status for KIT and PDGFRA from a molecular consultation service. In addition, 935 other mesenchymal tumors and 432 nonsarcomatous tumors were studied. Both DOG1 antibodies showed high sensitivity and specificity for GIST, with DOG1.1 showing some advantages. This antibody yielded positive staining in 370 of 425 (87%) scorable GIST, whereas CD117 was positive in 317 of 428 (74%) GIST and CD34 in 254 of 430 (59%) GIST. In GIST with mutations in PDGFRA, 79% (23/29) showed DOG1.1 immunoreactivity while only 9% (3/32) and 27% (9/33) stained for CD117 and CD34, respectively. Only 1 of 326 (0.3%) leiomyosarcomas and 1 of 39 (2.5%) synovial sarcomas among the 935 soft tissue tumors examined showed positive immunostaining for DOG1.1. In addition, DOG1.1 immunoreactivity was seen in fewer cases of carcinoma, melanoma, and seminoma as compared with KIT.     

胃肠间质瘤的诊治进展

经过近20年的研究,胃肠间质瘤(GIST)的诊断及治疗取得了巨大进步。手术是局限型无转移GIST的首选治疗方法。目前,对于进展期GIST患者来说,伊马替尼为一线靶向治疗药物,辅助治疗尚未完全结合不同的基因型进行个体化指导。期待未来更多的研究结果的公布能为临床治疗提供更好的指导。