胃肠道间质瘤诊治研究进展

胃肠道间质瘤（GIST）是起源于间叶组织的消化道肿瘤，确诊依靠病理学诊断，基因诊断提供了新的思路。GIST对放化疗不敏感，手术仍是主要的治疗方法，（甲磺酸）伊马替尼的问世给GIST的治疗带来了突破性的进展。     

胃肠道间质瘤的诊治研究进展

回顾总结近几年国内外关于胃肠道间质瘤（GISTs）在诊断治疗方面研究进展。GISTs的确诊需要依靠病理诊断及免疫组织化学，手术是GISTs主要的治疗方法，甲磺酸伊马替尼给GISTs的治疗带来了突破性的进展。     

胃肠道间质瘤

 胃肠道间质瘤（GIST）是近年来国内外关注的课题。其概念、发病机制、组织病理学、诊断与治疗方面均有很大进展，尤其是免疫组织学的发现和伊马替尼（商品名：格列卫）的靶向治疗，使GIST的诊断与治疗出现了新的飞跃，给这类患者带来福音，具有里程碑式的意义。     

胃肠道间质瘤的诊治

 引言胃肠道间质瘤 (gastrointestinalstromaltumor ,GIST)是一个随着临床病理技术发展而逐渐成熟的概念 ,是消化道最常见的间叶组织源性肿瘤。大量研究表明 ,以往诊断的胃肠道平滑肌肿瘤及神经鞘瘤大多数都属于GIST。目前比较公认的GIST的定义为 :GIST是胃肠道除外平滑肌肿瘤和神经鞘瘤及神经纤维瘤的、富于细胞且表达CD117的梭形、上皮样或多形性的间叶源性肿瘤 ,起源于向ICC(interstitialcellsofcajal)分化的未定形的间充质细胞。由于GIST确切的定义、组织来源、生物学行为、良恶性判断以及与胃肠道其他间叶性肿瘤的关系现存有不同意见 ,以致临床上诊断和治疗均较为困难。本文就GIST的目前诊治作一简要介绍。1　GIST的临床特征及生物学行为国外文献报道 ,GIST发病率约 1～ 2人 / 10万 ,占胃肠道肿瘤的 1%～ 4 % ,发病中位年龄在 5 5～ 6 5岁之间 ,4 0岁以前发病很少 ,儿童患此病更为罕见 ;男性稍多见或男、女性发病率相近 ;最常见于胃(6 0 %～ 70 % ) ,其次是小肠 (2 0 %～ 30 % ) ,结肠和直肠仅占 5...     

胃肠道间质瘤23例临床分析

目的 探讨胃肠道间质瘤的临床表现、诊断和治疗。方法 回顾性分析1995年11月至2004年1月收治23例胃肠道间质瘤的临床资料。结果 23例中病变部位在胃的9例，小肠8例，食管3例，直肠2例，十二指肠1例。全部行手术治疗，恶性10例，良性9例，交界性4例。18例术后随访1～99月，随访期内死亡8例。结论 胃肠道间质瘤临床表现无特异性，病理检查是确诊的依据，手术切除是最主要的治疗方法。     

胃肠道间质瘤32例临床分析

目的：提高对胃肠道间质瘤（gastrointestinal stomal tumor,GIST)的认识和诊治水平。方法：回顾分析总结32例GIST的临床资料,结果：患者平均年龄42．7岁,男女比为17：15,病灶均为单发,部位以胃及小肠最多见,分别为13例（40．6％）和15例（46．9％）,病理诊断良性21例（65．6％）,交界性5例（15．6％）,恶性6例（18．8％）,结合肿瘤临床生物学行为,重新划分为GIST良性18例（56．3％）,交界性4例（12．5％）,恶性10例（31．3％）,32例均获手术切除,一复发2例,肝转移4例,死亡4例。结论：GIST是一类具有恶性倾向的肿瘤,局部切除是足够而有效的治疗,术后应长期严密随访,对复发和／或转移者应持积极态度,多次姑息切除,辅以TACE可望延长病人生存期。     

胃肠道间质瘤诊断治疗进展

胃肠道间质瘤缺乏特异性的临床表现,术前诊断主要依靠相关辅助检查。随着相关辅助检查设备和技术的进步,胃肠道间质瘤的术前诊断率也得到相应提升。近年来由于新型手术器械的发明与使用,胃肠道间质瘤的外科治疗方式也在发生着变化。新型靶向药物的应用为胃肠道间质瘤患者提供了更多的治疗选择。作者就胃肠道间质瘤术前诊断及治疗现状与进展进行了综述。     

胃肠道间质瘤诊断方法的研究进展

胃肠道间质瘤（gastrointestinal stromal tumor,GIST）是起源于胃肠道间叶组织的肿瘤,由于GIST存在恶性潜能,且多数GIST患者无明显临床症状,所以GIST的早期发现、诊断和治疗显得尤为重要。GIST通常在内窥镜、超声内镜（endoscopic ultrasound,EUS）检查中发现。GIST的诊断取决于形态学和免疫组织化学染色,因此组织样本的充足性是其关键。近年来,新的成像技术的应用和分子生物学的发展提高了GIST的诊断准确率,并为GIST的预后及辅助治疗提供了依据。     

胃肠道间质瘤35例诊治分析

目的 总结胃肠道间质瘤的临床诊断与治疗方法.方法 回顾性分析35例胃肠道间质瘤患者的临床和病理资料.结果 33例胃肠道间质瘤患者行手术治疗.其中极低危险性6例,低危险性10例,中危险性8例,高危险性9例.25例患者获随访1～3 a,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,2例术后口服甲磺酸伊马替尼,其余20例患者术后定期复查,未再进行相关治疗.结论 胃肠道间质瘤确诊依赖于术后病理和免疫组化检查,手术是其主要治疗方法,分子靶向治疗具有辅助作用.     

31例胃肠道间质瘤的临床诊治分析

目的：探讨胃肠道间质瘤的诊断和治疗。方法：收集经手术病理证实的31例胃非上皮肿瘤，全部经CD117、CD34检测。其中18例行近侧胃切除，4例行全胃切除，9例行胃远侧切除，切除范围在5crn以上。并对其中27例随访。结果：31例100％胃非上皮肿瘤CD117、25例81％CD34，其中良性12例、恶性19例。随访27例(良性11例、恶性16例)，良性中6例随访6a～10a未复发，5铡2a～5a无复发，恶性16例，5a生存率47％。结论：胃的非上皮肿瘤应统称为胃肠道间质瘤。手术切除仍是其主要的治疗方法。     

胃肠道间质瘤临床病理特点及诊治分析

目的 探讨胃肠道间质瘤(GIST)临床病理特点及诊治情况.方法 对31例GIST患者的临床资料进行回顾性分析.结果 全部患者均行手术治疗.31例GIST患者发生部位以胃(19例61.3%)和空肠(6例19.3%)为主.首发症状以腹痛、腹胀(20例64.5%)和消化道出血(12例38.7%)、腹部包块(8例25.8%)为主要表现.病理报告良性13例、潜在恶性2例、恶性16例.免疫组化CD117阳性28例(90.3%),CD34阳性26例(83.9%).结论 (1)GIST消化道症状无特异性,术前确诊率低,易造成误诊;(2)CD117和CD34阳性可以作为GIST的诊断标志;(3)治疗应以局部切除为主,恶性者应扩大切除范围.     

甲磺酸伊马替尼治疗胃肠道间质瘤的研究进展

胃肠道间质瘤（GIST）是胃肠道及腹腔最常见的间叶源性肿瘤,对常规的放疗、化疗均不敏感。外科手术是局限性GIST患者的主要治疗方式,但术后复发率较高。对于术前、术后辅助、复发、转移及不能手术切除的患者,酪氨酸激酶抑制剂甲磺酸伊马替尼对其有较好的治疗效果。本文对甲磺酸伊马替尼治疗胃肠道间质瘤的研究进展作一综述。     

Diagnostic and treatment strategy for small gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini‐GISTs) (1‐2 cm) and pathologic GISTs (micro‐GISTs) (<1 cm) are frequently reported. Most mini‐GISTs and almost all micro‐GISTs of the stomach may exhibit benign clinical behavior, and only mini‐GISTs with high‐risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini‐GISTs with high‐risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow‐up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal and colorectal GISTs, surgery is indicated irrespective of size because of their greater malignant potential. Otherwise, mini‐GISTs without high‐risk features, micro‐GISTs, and small submucosal tumors measuring <5 cm without high‐risk features may be followed by periodical endoscopic ultrasonography. Although surgical approaches and operative methods are selected according to tumor size, location, growth pattern, and surgical teams, laparoscopic surgery has produced similar oncologic outcomes and is less invasiveness compared with open surgery. After resection, pathologic examination for diagnosis and risk assessment is mandatory, and genotyping is also recommended for high‐risk GISTs. Endoscopic resection techniques, although feasible, are not routinely indicated for most mini‐GISTs or micro‐GISTs. Cancer 2016;122:3110–8 . © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.     

Genetic aberrations of gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm in the gastrointestinal tract and is associated with mutations of the KIT or PDGFRA gene. In addition, other genetic events are believed to be involved in GIST tumorigenesis. Cytogenetic aberrations associated with these tumors thus far described include loss of 1p, 13q, 14q, or 15q, loss of heterozygosity of 22q, numeric chromosomal imbalances, and nuclear/mitochondrial microsatellite instability. Molecular genetic aberrations include loss of heterozygosity of p16(INK4A) and p14(ARF), methylation of p15(INK4B), homozygous loss of the Hox11L1 gene, and amplification of C-MYC, MDM2, EGFR1, and CCND1. GISTs in patients with neurofibromatosis type 1 appear to lack the KIT and PDGFRA mutations characteristic of GISTs and may have a different pathogenetic mechanism. Gene mutations of KIT or PDGFRA are critical in GISTs, because the aberrant versions not only are correlated with the specific cell morphology, histologic phenotype, metastasis, and prognosis, but also are the targets of therapy with imatinib and other agents. Furthermore, specific mutations in KIT and PDGFR appear to lead to differential drug sensitivity and may in the future guide selection of tyrosine kinase inhibitors. Activation of the receptor tyrosine kinases involves a signal transduction pathway whose components (mitogen-activated protein kinase, AKT, phosphoinositide 3-kinase, mammalian target of rapamycin, and RAS) are also possible targets of inhibition. A new paradigm of classification, integrating the standard clinical and pathological criteria with molecular aberrations, may permit personalized prognosis and treatment.     

人胃肠道和胃肠外间质瘤microRNA表达谱的比较

目的:比较消化道原发胃肠道间质瘤(gastrointestinal stromal tumors,GISTs)与胃肠外间质瘤(extra-gastrointestinal stromaltumors,EGISTs)microRNA(miRNA)表达谱的差异,分析其与肿瘤原发部位、突变类型等因素间的关系。方法:收集西京医院病理科的8例石蜡样本(5例GISTs、3例EGISTs),利用安捷伦人miRNA表达谱芯片(芯片覆盖866个人miRNA)进行分析。同时通过PCR扩增后直接测序,明确8例样本的基因突变类型。结果:芯片数据经非监督层次聚类分析,显示8例样本分为3簇,具有相同突变类型的1例胃部GIST和1例EGIST构成第1簇,2例胃部GISTs构成第2簇,其余4例(2例小肠GISTs和2例EGISTs)构成第3簇。将5例GISTs按部位分成2组(胃部和肠道),3例EGISTs分别加入miRNA表型相似的组,2组比较后发现12个miRNA表达有显著差异;预测的靶基因多数参与KIT/PDGFRA的信号转导,其中有5个在肠道组显著下调,部分已有报道与肿瘤的演进相关。比较GISTs和EGISTs的表达谱,发现仅有3个miRNA的表达差异具有统计学意义。结论:GISTs和EGISTs的miRNA表型相似,均与肿瘤部位及突变类型关系密切,因此miRNA表型的分析可能有助于GISTs在分子水平上的分类。     

Surgery including liver resection for metastatic gastrointestinal stromal tumors or gastrointestinal leiomyosarcomas

BACKGROUND: In recent years, imatinib mesylate (STI 571), a tyrosine kinase inhibitor, has shown short-term clinical usefulness for gastrointestinal stromal tumor or gastrointestinal leiomyosarcoma (GIST). The value of surgical resection, including hepatectomy, for metastatic GIST remains unknown. Our aim was to evaluate the outcome of surgical resection, including hepatectomy, for metastatic GIST at a single institute. METHODS: Eighteen patients who underwent hepatectomy for metastatic GIST were identified and the clinicopathological data of these patients were analyzed retrospectively. RESULTS: The primary site of GIST included stomach in 10, duodenum in five, ileum in two and esophagus in one patient. A hemihepatectomy or greater resection was undertaken in eight patients. Six patients underwent simultaneous resection for primary and hepatic disease. There was no in-hospital mortality in this series. The post-hepatectomy 3- and 5-year survival rates were 63.7 and 34.0% respectively, with a median of 36 (17-227) months. Recurrence after the initial hepatectomy was documented in 17 patients (94%), and metastatic mass of the remnant liver developed in 15 of these 17 patients (88%). Three patients survived >5 years after the initial hepatectomy who underwent multiple surgical resections during this period. No clinicopathological characteristic was a significant predictive factor for survival. CONCLUSIONS: Multiple surgical resections, including hepatectomy, may contribute to important palliation in selected patients with metastatic GIST. Surgical cure seems to be difficult due to the high frequency of repeat metastasis to various sites. Therefore, adjuvant therapy must be required in the treatment of metastatic GIST.     

Tailored management of primary gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma and can form along the entire gastrointestinal tract. Over the last 20 years, considerable advances have been made in our understanding of the biology of GISTs. The advent of tyrosine kinase inhibitors has provided effective medical therapy for the first time. In fact, given that GIST typically is driven by either a KIT or PDGFRA gene mutation, it has become a paradigm of targeted molecular therapy. In addition, diagnostic and surgical techniques have been refined. Here, the critical aspects of primary GISTs and how they are now managed with an integrated approach are summarized. Treatment plans are developed based on specific pathologic and molecular features of the tumor. The authors outline the general principles of therapy and highlight some of the nuances. Particular focus is given to diagnosis, surgical considerations, and the use of preoperative and postoperative tyrosine kinase inhibitors.