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甲磺酸伊马替尼(格列卫)治疗转移性胃肠道间质瘤(GISTs)的外科治疗综述

A review of the surgical management of metastatic gastrointestinal stromal tumours (GISTs) on imatinib mesylate (Glivec).

作者信息

Barnes G, Bulusu V R, Hardwick R H, Carroll N, Hatcher H, Earl H M, Save V E, Balan K, Jamieson N V

机构信息

Directorate of Surgery, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK.

出版信息

Int J Surg. 2005;3(3):206-12. doi: 10.1016/j.ijsu.2005.04.001. Epub 2005 Sep 12.

Abstract

Gastrointestinal stromal tumours (GISTs) are defined as a group of C-KIT positive mesenchymal tumours of the gastrointestinal tract. Although they may arise throughout the gut, the commonest sites are stomach and small intestine. Over 80% of metastases are to the liver and omentum. Targeted therapy (imatinib) can inhibit C-KIT and thereby aberrant tumoural proliferation. Imatinib may induce shrinkage of lesions and cystic change. Such physical changes often correspond with reduced metabolic activity demonstrated by (18-FDG)PET scans. These changes may enable metastatectomy reducing tumour pain and the risk of haemorrhage and rupture in the short term. In the long term, resection may lessen the risk of recurrence by removing potentially resistant clones. The precise role of palliative resection for GIST metastases on imatinib remains unclear. Imatinib has changed the natural history of metastatic GISTs, with increased survival times. Surgery remains an important management strategy in the metastatic setting because complete pathological responses are rare with imatinib. Surgery is likely to provide the best palliation, greatest reduction in tumour burden and eliminate resistant clones. A multidisciplinary team approach with expertise concentrated in a few centres specialising in the management of these rare tumours is vital to the successful outcome. Future issues regarding the management of differential response of the metastases to imatinib are highlighted. With the emergence of techniques enabling identification of the precise mutational status of the C-KIT oncogene, the imatinib/surgery sequence could be tailored to the type of C-KIT mutation.

摘要

胃肠道间质瘤(GISTs)被定义为一组胃肠道的C-KIT阳性间充质肿瘤。尽管它们可能出现在整个肠道,但最常见的部位是胃和小肠。超过80%的转移灶位于肝脏和网膜。靶向治疗(伊马替尼)可抑制C-KIT,从而抑制异常的肿瘤增殖。伊马替尼可能会导致病变缩小和囊性变。这些物理变化通常与(18-FDG)PET扫描显示的代谢活性降低相对应。这些变化可能使转移灶切除术在短期内减轻肿瘤疼痛以及降低出血和破裂风险。从长远来看,切除可能通过去除潜在的耐药克隆来降低复发风险。姑息性切除对伊马替尼治疗的GIST转移灶的确切作用仍不清楚。伊马替尼改变了转移性GISTs的自然病程,延长了生存时间。手术在转移性疾病的治疗中仍然是一项重要的管理策略,因为伊马替尼很少能带来完全的病理缓解。手术可能提供最佳的姑息治疗效果,最大程度减轻肿瘤负荷并消除耐药克隆。一个多学科团队方法,其专业知识集中在少数几个专门管理这些罕见肿瘤的中心,对于取得成功结果至关重要。文中强调了关于转移灶对伊马替尼不同反应的管理的未来问题。随着能够识别C-KIT癌基因精确突变状态的技术的出现,伊马替尼/手术顺序可以根据C-KIT突变类型进行调整。

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