进展期胃肠间质瘤的合理诊疗策略

随着对胃肠间质瘤（GIST）认识的提高。临床上诊断为GIST患者的比例逐年升高。早期GIST行手术完整切除预后良好,而进展期GIST无论是在单纯手术治疗阶段、单纯伊马替尼靶向治疗阶段还是手术联合伊马替尼治疗阶段,手术后再复发、伊马替尼耐药和靶向药物多重耐药等问题仍然是目前治疗的难点。大量的临床证据显示．合理的治疗策略可以改善进展期GIST患者的预后。进展期GIST绝不能单纯认为是内科或者外科疾病,需要包括肿瘤外科、肿瘤内科、病理科、影像科和介入科等多学科协作组的综合诊疗。本文结合目前国内外最新研究进展．基于循证医学证据和笔者经验．提出进展期GIST的合理诊疗策略．以期达到早期发现、初期预防和恰当管理的目标．从而改善患者预后．延长生存期．     

靶向治疗时代胃肠间质瘤的外科理念

胃肠间质瘤（GIST）是胃肠道最常见的间质肿瘤。长期以来外科治疗是首选也是惟一的治疗手段,随着GIST靶向治疗的到来,外科治疗模式也不断发展。无论是手术原则、手术技术、手术时机,还是手术联合靶向治疗为主的多学科治疗模式,都在循证医学的基础上进行了细化和发展。外科完全切除仍是原发局限可切除GIST治疗的金标准。而对于进展期GIST,靶向治疗的介入彻底改变了此类病人的预后。对伊马替尼治疗有效的进展期GIST病人,联合外科手术切除为主的综合治疗模式是目前研究的热点。     

对复发转移性胃肠间质瘤手术还是不手术

复发转移性胃肠间质瘤（GIST）的处理是目前临床治疗的一大难题。国际上一些大型临床试验显示．伊马替尼治疗可显著改善复发转移GIST患者的生存期。而手术联合伊马替尼已成为转移GIST的理想治疗方法。然而．两者如何联合应用尚存在争议。伊马替尼可能影响凝血机制．因此,建议术前1周停药。细胞减灭术在复发转移性GIST中有一定的临床疗效,可与靶向药物联合应用。而复发转移GIST的临床试验尚需进一步评价。     

复发性胃肠间质瘤诊治对策及评价

原发性胃肠间质瘤（GIST）完整手术切除后出现复发是临床常见问题,包括局部原位复发、腹腔播散种植和远隔脏器转移3种类型。伊马替尼等靶向药物的问世改善了复发性GIST的治疗方式和结局。应用影像学手段精确评估复发病灶状态,仔细了解病人服药情况和一般身体状况有助于科学选择治疗策略。伊马替尼是复发性GIST的首选治疗,但很少出现病理学完全缓解,连续治疗应持续到病人无法耐受或疾病出现进展。结合靶向治疗,适宜的外科手术切除复发或转移病灶能给病人带来生存获益。     

进展期胃肠间质瘤的诊治进展

目的总结进展期胃肠间质瘤(GIST)的诊断及治疗进展。方法通过检索相关文献资料,就近年来关于进展期GIST的诊断及治疗进展情况进行综述。结果进展期GIST的诊断主要依靠CT、MRI等影像学以及内镜或超声内镜等辅助检查,考虑术前行伊马替尼治疗的GIST患者可以行穿刺活检确定诊断。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,其次为舒尼替尼和其他新型靶向药物。在靶向药物治疗的基础上联合手术、射频消融、栓塞化疗等多学科综合治疗能给进展期GIST患者带来更多的临床获益。结论 GIST易转移,临床医生应做到早诊断、早治疗。在靶向药物治疗的基础上根据患者的具体情况采取个体化治疗。     

晚期胃肠道间质瘤靶向治疗后的外科治疗

目的探讨手术对于伊马替尼治疗后晚期胃肠道间质瘤（GIST）患者的临床疗效。方法回顾性分析13例术前予以伊马替尼治疗,然后接受手术切除的晚期GIST患者的临床资料。结果13例伊马替尼治疗后手术切除的患者中,有3例为局部晚期原发肿瘤,10例为复发或转移患者。治疗有效（RD组）的5例中有4例、疾病进展（PD组）的8例中有1例共计5例（38．5％）患者肿瘤获得完全切除。RD组无疾病进展生存（PFS）为24．8个月,PD组的PFS为2．8个月,两组比较,差异有统计学意义（P〈0．01）。RD组和PD组患者的总生存率比较,差异无统计学意义（P〉0．05）。结论在对伊马替尼治疗有效的晚期GIST患者中,伊马替尼治疗后再行外科手术切除是可行的。     

胃肠间质瘤治疗进展

胃肠间质瘤（GIST）是胃肠道最常见的间叶来源肿瘤。大部分患者存在c-kit或PDGFRa基因突变。手术根治性切除是治疗胃肠间质瘤的基石,但是术后复发率较高。近年来,以伊马替尼为代表的靶向治疗大大提高了GIST治疗效果。对于手术可以切除的患者,手术切除联合新辅助或辅助治疗改善了高危患者的预后：对于手术不可切除的患者,靶向治疗也有效地抑制、延缓了病情的进展。     

胃肠间质瘤的外科及靶向治疗策略

众所周知,伊马替尼等靶向药物改变了胃肠间质瘤（GIST）病人的治疗策略。但目前伊马替尼等的应用已从单纯药物治疗模式向与外科治疗联合应用的模式转变。PET?CT显像结果与临床症状缓解相一致,可早期评价GIST病人的疗效。动态增强超声造影已成为GIST靶向药物治疗疗效评价新的功能成像方法。对于高危的GIST病人,术后应采用伊马替尼辅助治疗1~2年。新辅助治疗在GIST中的应用已被广泛接受。目前认为对于伊马替尼耐药的病例,应用舒尼替尼治疗是安全可接受的。     

酪氨酸激酶抑制剂联合手术治疗转移性胃肠间质瘤

目的 探讨酪氨酸激酶抑制剂（TKI）甲磺酸伊马替尼或舒尼替尼联合手术治疗晚期转移性胃肠间质瘤（GIST）的临床疗效.方法 回顾分析中山大学附属第一医院2007年6月至2009年12月接受TKI治疗后进行手术治疗的转移性GIST患者临床病理资料.结果 共计15例转移性GIST患者在TKI治疗后接受肿瘤切除手术.术前TKI治疗反应分别为疾病控制6例（40.0%）,局限性进展4例（26.7%）,全面性进展5例（33.3%）.手术相关并发症发生率20.0%.全组患者中位无进展生存期18.7个月.其中疾病控制和局限性进展组患者术后无进展中位生存期25.0个月,全面性进展组则仅为3.0个月（P＜0.01）;疾病控制和局限性进展组患者至今仍全部存活,而全面性进展组患者中位总生存期为10.5个月（P＜0.01）.结论 靶向治疗后,疾病控制或局限性进展的晚期转移性GIST患者行手术治疗安全有效,而全面性进展患者手术治疗不能改善其预后,应谨慎选择.     

靶向治疗高危胃肠道间质瘤的临床疗效

目的:探讨应用伊马替尼治疗高危胃肠道间质瘤(GIST)的临床疗效。方法:回顾性分析2010年1月—2015年6月收治的56例接受伊马替尼靶向治疗的高危GIST患者临床资料,并对疗效进行分析。结果:19例无手术切除机会的患者经伊马替尼(400 mg/d)治疗6~8个月后,无完全缓解(CR)者,部分缓解(PR)14例,疾病稳定(SD)4例,疾病进展(PD)1例;7例(36.8%)PR患者获得手术切除机会。35例行手术切除后服用伊马替尼(400 mg/d)1年,随访3例复发,1年复发率8.6%;2例终断服药,无法评估疗效。结论:伊马替尼治疗GIST疗效肯定,对于高危GIST患者,术前新辅助化疗能让无法手术切除的肿瘤获得手术机会,术后辅助化疗可能提高无瘤生存率,不良反应较轻能够耐受。     

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??Surgery management for patients with gastrointestinal stromal tumor in the era of targeted therapy YE Ying-jiang, WANG Shan. Department of Gastrointestinal Surgery, Peking University People’s Hospital, Beijing 100044, China
Corresponding author: WANG Shan, E-mail: shwang60@263.net.
Abstract Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract. For long time, the only proven therapy was surgery. The use of imatinib for targeted therapy has marked a new era in treatment. The surgical management of GIST has rapidly changed in the era of targeted therapy, and gotten advances in surgical principle, surgical technique and time of surgery, based on evidence-based medicine. Multidisciplinary approaches included targeted treatment and surgical treatment are the future to successfully treat patients with GIST. Complete resection without tumor rupture is still gold standard of curative treatment for localized, resectable, primary disease. In advanced patients, imatinib has been the standard treatment. For patients with advanced GIST responsive to imatinib, combined surgical plus targeted therapy may be most effective and improve survival.     

Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib

Background Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated. Methods Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. Results Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery. Conclusions Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs. Presented in part at the Annual Meeting of the Society of Surgical Oncology, Atlanta, GA, March 2005.     

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目的探讨对伊马替尼继发耐药的复发和转移的晚期胃肠道间质瘤(gastrointestinal stromal tumors,GIST)的治疗策略。方法回顾性分析复旦大学附属中山医院2000—2009年对伊马替尼继发耐药的复发和转移的晚期8例GIST病人的临床资料。结果所有病人均行手术治疗,完整切除原发肿瘤后,肿瘤复发和(或)转移,口服伊马替尼治疗产生继发耐药,采取手术切除复发和转移灶(特别是耐药病灶)联合伊马替尼等靶向治疗为主的综合治疗模式,均获得较好的治疗效果。1例死亡,存活96个月;其余7例仍存活,目前存活时间65～145个月,平均98.6个月。结论伊马替尼继发耐药的复发和转移的晚期GIST,选择手术联合酪氨酸激酶抑制剂靶向治疗为主的多学科综合治疗模式,参考肿瘤的基因状态,采取个体化治疗,可取得较好的疗效。     

Surgery for gastrointestinal stromal tumour in the post-imatinib era

Gastrointestinal stromal tumour (GIST) is a rare tumour. Historically, surgery has been the only effective treatment. The prognosis of patients with gastrointestinal stromal tumour is poor. Even after apparently 'curative' surgical resection more than 50% of patients relapse. The development of an effective novel targeted therapy against GIST (imatinib mesylate) is a success story of molecular biology that has dramatically altered the management of patients with these tumours. However, as follow up of patients who have initially responded to imatinib has increased, it has become evident that such hopes of cure were premature because responses to imatinib are of limited duration. Unresolved issues include the role of imatinib as an induction (neo-adjuvant) therapy prior to surgery, or as adjuvant treatment after surgery, the role of surgery in patients with a differential or partial response and the role of surgery in patients with isolated metastatic disease. In the present paper the biology and natural history of GIST are reviewed, and the complexities of surgical management that exist in the context of an effective, but not curative, biological therapy, are addressed.     

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.     

对伊马替尼继发耐药的晚期胃肠道间质瘤治疗策略探讨

目的 探讨对伊马替尼继发耐药的复发和转移的晚期胃肠道间质瘤（gastrointestinal stromal tumors, GIST）的治疗策略。方法 回顾性分析复旦大学附属中山医院2000—2009年对伊马替尼继发耐药的复发和转移的晚期8例GIST病人的临床资料。结果 所有病人均行手术治疗,完整切除原发肿瘤后,肿瘤复发和（或）转移,口服伊马替尼治疗产生继发耐药,采取手术切除复发和转移灶（特别是耐药病灶）联合伊马替尼等靶向治疗为主的综合治疗模式,均获得较好的治疗效果。1例死亡,存活96个月;其余7例仍存活,目前存活时间65~145个月,平均98.6个月。结论 伊马替尼继发耐药的复发和转移的晚期GIST,选择手术联合酪氨酸激酶抑制剂靶向治疗为主的多学科综合治疗模式,参考肿瘤的基因状态,采取个体化治疗,可取得较好的疗效。