胃肠道间质瘤的腹腔镜外科治疗

胃肠道间质(gastrointestinal stromal tumor,GIST)近年随着免疫组化及电镜技术的发展而提出的新的病理学概念,其包括以往的胃肠道平滑肌瘤、平滑肌肉瘤、神经鞘瘤等。GIST是一种具有潜在恶性的肿瘤,手术切除是目前治疗GIST最有效的方案,现对我院自1998年起收治的8例GIST病人进行分析,探讨其诊断及腹腔镜手术治疗的体会。     

Outcome following surgical therapy for gastrointestinal stromal tumors

We have pursued an approach of complete resection for patients with gastrointestinal stromal tumors (GISTs), including multivisceral resection, for patients with disease involving adjacent organs. We have also extended the limits of resection to include patients with metastatic disease who were treated with imatinib mesylate. The aim of this study is to report the outcomes and prognostic factors associated with this clinical approach. Study subjects were identified using the pathology database at our institution; for inclusion in the study group, patients must have undergone surgical resection for a KIT-positive gastrointestinal stromal tumor between January 1992 and March 2004. We calculated survival by using the Kaplan-Meier method. Univariate and multivariate analysis was performed using log-rank analysis and the Cox proportional hazards model. Thirty-four patients met the study criteria. Fifty-nine percent of patients had GISTs of gastric origin, 20.6% had duodenal GISTs, and the remainder was comprised of a variety of other sites. Twenty-two (64.7%) patients underwent single-organ resection, and 12 patients (35.3%) underwent multivisceral resection. Estimated actuarial survival at 5 years was 65.2%. Seven patients (five patients with metastases, one patient with locally advanced disease, and one patient with organ-confined disease) received imatinib mesylate. Independent predictors of poor survival included incomplete resection, metastatic disease at presentation, and high mitotic index. Mitotic index and the presence of metastases remain the primary predictors of postoperative survival. Complete surgical resection, even if multivisceral resection is required, is associated with improved survival. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation).     

腹腔镜手术治疗胃和小肠胃肠间质瘤疗效分析

目的探讨原发局限性胃和小肠胃肠间质瘤（GIST）腹腔镜手术切除的可行性和短期效果。方法回顾性分析2010年10月至2013年4月间在中山大学附属第一医院接受腹腔镜手术治疗的20例胃GIST和6例小肠GIST患者的临床病理资料。结果26例患者中行手辅助腹腔镜胃GIST切除3例,其余23例均行腹腔镜辅助切除手术,无一例中转开腹。根据肿瘤部位和生长方式,行胃局部切除术18例,远端胃部分切除2例,小肠部分切除6例。肿瘤直径（4．5±1．6）cm,手术时间（96．0±28．2）min,术中出血量（49．6±38．6）ml。术后胃肠功能恢复时间（2．3±0．7）d,术后住院时间（6．8±1．9）d。术后吻合口出血1例,保守治疗治愈。术后病理按照改良NIH标准显示,极低度恶性危险（极低危）1例（3．8％）,低危13例（50．0％）,中危9例（34．6％）,高危3例（11．5％）。术后随访3～32（中位数15）月,未发现复发或死亡病例。结论原发局限性胃或小肠GIsT腹腔镜切除创伤小、恢复快,短期效果满意。     

Aggressive surgery for liver metastases from gastrointestinal stromal tumors

Background/Purpose. The utility of hepatectomy for patients with metastatic liver tumors from gastrointestinal stromal tumors (GISTs) was evaluated in the present study. Methods. Between 1989 and 2001, ten patients with liver metastases from GIST (four men and six women; age, 34–77 years) underwent hepatectomy at our hospital. All patients underwent complete resection of the primary tumor and hepatectomy with or without microwave coagulation therapy (MCT) for all detectable hepatic tumors. Results. The median survival time after hepatectomy was 39 months (range, 1 to 96 months). There was one postoperative death. One patient is still alive with relapse of hepatic tumors, and the remaining eight patients died of disease (liver in six, peritoneum in one, and bone in one). Relapse of hepatic tumors occurred in seven patients. The disease-free rate after hepatectomy was 22% at 2 years and 11% at 5 years. The survival times of the four patients who received hepatic arterial chemoembolization for recurrent hepatic metastases were 7 months (still alive), 17, 23, and 28 months (average, 19 months). Conclusions. Our data suggest that aggressive surgery (hepatectomy and MCT) for all detectable hepatic tumors and hepatic arterial chemoembolization for recurrent hepatic metastases improve survival. Received: March 31, 2002 / Accepted: September 24, 2002 RID="*" ID="*" Offprint requests to: Y. Shima     

Management of gastrointestinal stromal tumors

A gastrointestinal stromal tumor (GIST) is a rare mesenchymal malignancy of the gastrointestinal (GI) tract. Malignant GISTs were first defined as a separate entity from a collection of nonepithelial malignancies of the GI tract in the 1980s and 1990s based on pathologic and clinical behavior. The discovery of activating KIT mutations as a near-uniform occurrence in these tumors greatly influenced the classification [1] and revolutionized therapeutic management of these tumors. To meet the next challenges, newer tyrosine kinase inhibitors and targeted agents are being developed with the goal of providing improved response rates or alternative therapies for patients progressing on established agents. In this article, the authors describe the management of GISTs, concentrating on surgical management and targeted therapies.     

胃肠道间质瘤的预后

随着对胃肠道间质瘤（gastrointestinal stromal tumor，GIST）分子生物学的认识和激酶抑制剂类靶向治疗药物的诞生，GIST的预后也发生了明显改善，疾病缓解率和手术切除率显著提高，生存期延长。不同的临床病理因素和治疗方法对GIST病人生存期具有根本影响。     

胃肠道及胃肠道外间质瘤216例临床病理学特点分析

目的 探讨胃肠道间质瘤（gastrointestinal stromal tumor,GIST）和胃肠道外间质瘤（extragastrointestinal stromal tumor,EGIST）的临床病理和免疫组化特点及其诊断标准。方法 回顾性分析天津医科大学总医院及第二医院2000-2009年已确诊的216例GIST和EGIST病人的临床资料,其中,天津医科大学总医院175例,天津医科大学第二医院41例。 结果 216例病人中,男性112例,女性104例,男女比例为1.077 : 1;发病年龄15~91岁,中位年龄58岁;肿瘤原发于胃肠道者182例,以胃多见;胃肠道外者34例,以肠系膜多见。肿瘤直径0.8～30.0cm,由梭形细胞和上皮样细胞组成,细胞排列呈交叉束状、漩涡状及巢状。214例CD117呈阳性。临床多表现为消化道出血、腹部疼痛、腹部肿块及肠梗阻等症状。 结论 GIST较EGIST多见;胃肠道以中、高度危险者多见,胃肠道外以高度危险者多见。临床治疗原则首选广泛手术切除。     

腹腔镜手术治疗胃肠道间质瘤

胃肠道间质瘤（gastrointestinal stromal turnors,GIST）是一种较为少见的胃肠道非上皮源性的间充质肿瘤。由于其组织来源复杂，以往常被诊断为平滑肌瘤，平滑肌肉瘤或神经鞘瘤等。94％的GIST由于c—kit基因突变，导致酪氨酸激酶受体kit过度表达。因此，目前主要依靠其分子特点以及免疫组化表现对GIST作出病理诊断。     

The effect of surgery and grade on outcome of gastrointestinal stromal tumors

HYPOTHESIS: Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. DESIGN AND SETTING: A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. PATIENTS: Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. MAIN OUTCOME MEASURES: Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. RESULTS: Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. CONCLUSION: Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor prognosis, with decreased survival, and increased local and/or distant recurrence.     

胃肠间质瘤的外科治疗

近年来,关于胃肠间质瘤(gastrointestinal stromal tumor,GIST)的研究已越来越受到国内外医学界的重视。2005年美国NCI(National Cancer Institute)的一项回顾性调查报告显示,年发病率为0.68/10万;瑞典报道年发病率为14.5/100万。我国尚无GIST发病率的调查数据。GIST具有肿瘤边界清楚、质地较脆、常有假包膜、淋巴转移少     

基因突变与胃肠道间质瘤研究进展

摘要：c kit及血小板源性生长因子受体α（platelet derived growth factor receptor alpha,PDGFRA）的功能增强性突变是导致胃肠道间质瘤（GIST）的主要原因。c kit基因及PDGFRA基因的突变位点及突变方式对肿瘤的临床特征有明显影响。笔者就基因突变与GIST的关系进行综述。     

胃肠管间质瘤的综合治疗进展

胃肠管间质瘤为一种胃肠管最常见的原发性间质细胞肿瘤,具有偶发性及无症状性的特点.外科治疗仍是无转移胃肠管间质瘤的首选治疗.但术后复发率较高.针对肿瘤的分子生物学特点,通过联合分子靶向药物的治疗,能够改善该病的预后.     

胃肠道间质瘤的鉴别诊断

胃肠道间质瘤（gastrointestinal stromal tumors，GIST）的名称提出后，其概念和内涵经历了不同时期的演变。在广义的GIST概念影响下，将GIST诊断为平滑肌肿瘤、可能平滑肌肿瘤、可能神经鞘肿瘤、未定分化肿瘤，不但从中英文字面上，而且一定程度从概念上导致了GIST与胃肠道间叶源性肿瘤（gastrointestinal mesenchymal tumors，GIMT）的混淆。此外，部分研究者还提出了胃肠道自主神经瘤（gastrointestinal autonomic tumors，GANT）的概念。现在，GIST特指由c—kit基因或PDGFRa基因驱动、由梭形或上皮样细胞组成、表达CD117、向卡哈尔细胞分化的消化道最常见的GIMT。是适合分子靶向药物格列卫（STI-571，imatinib mesylate，gleevec，norvatis）治疗的肿瘤之一。     

Laparoscopic management of gastrointestinal stromal tumors

Background Surgery remains the standard for nonmetastatic gastrointestinal stromal tumors (GISTs). Laparoscopic surgery should be considered for these tumors as their biologic behavior lends them to curative resection without requiring large margins or extensive lymphadenectomies. Methods A retrospective review was performed of patients who underwent laparoscopic treatment of GISTs by surgeons at the Mount Sinai Medical Center from 2000-2005. Records were reviewed with respect to patient demographics, medical history, diagnostic workup, operative details, postoperative course, and pathologic characteristics. Results Laparoscopic surgery was attempted in 43 patients with GISTs. The average age was 65 years and 21 were women. Fifty-six percent of patients presented with anemia or gastrointestinal bleeding. The tumors were located in the stomach (65%) and in the small bowel (35%). The mean tumor sizes were 4.6 cm (stomach) and 3.7 cm (small bowel). Gastric operations included laparoscopic wedge (29%), sleeve (21%), and partial (29%) gastrectomies. The three gastric conversions were due to local invasion of tumor into adjacent organs or proximity to the gastroesophageal junction. Small bowel operations included laparoscopic resections with extracorporeal (47%) and intracorporeal anastamoses (33%). Conversion in small bowel operations was associated with coincidental pathology in addition to the GIST. This consisted of an associated bowel perforation and a synchronous colonic carcinoma. There was one mortality and a 9% morbidity rate, including an evisceration requiring reoperation. All tumors were pathologically confirmed with CD117 immunohistochemistry. Conclusions In light of their biologic behavior, GISTs should be considered for laparoscopic resection. This minimally invasive approach to these tumors can be performed safely and reliably.     

Laparoendoscopic management of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) account for 1% to 3% of all resected gastric tumors and are the most common submucosal mass found in the stomach. The preoperative characterization of malignancy is often difficult, and excision is the most common management option. Reported techniques are endoscopic, laparoendoscopic, and laparoscopic. The excision can be intracorporeal or extracorporeal, intragastric or transgastric. Different methods are used based on the location of the tumor. We present two cases of a three-port laparoendoscopic transgastric technique. This method can be used safely for both anteriorly and posteriorly located lesions.     

胃肠道间质瘤的规范化治疗

Gastrointestinal stromal tumors (GISTs) is a subset of mesenchymal tumors and represents the most common mesenchymal neoplasm of gastrointestinal tract.In the last decade,GISTs has become well known because of the effectiveness of imatinib mesylate.The molecular targets for tyrosine kinase receptor inhibitor are not only of importance for the treatment of patients but also useful for the development of a novel drug modalities and new strategies in basic cancer therapy.The improved understanding of the molecular mechanism of GISTs has made its diagnosis standardized.Many multicenter phase Ⅱor phase Ⅲ clinical trials have been completed to establish the role of adjuvant and neoadjuvant therapy.It is important to select the correct management strategy,which is multidisciplinary,integrated,and individualized.This paper provides an overview of the rational treatment of GISTs at present.     

胃肠道间质瘤的内科治疗

胃肠道间质肿瘤（gastrointestinal stromal tumor，GIST）是胃肠道中一种特殊的肿瘤。近年来随着对GIST分子病理的深入研究和靶向药物的应用，GIST越发引起人们的关注。在GIST传统治疗中，手术切除至今仍是GIST惟一根治性治疗手段。但复发率极高。而放射治疗很少应用于GIST的治疗，因为其邻近器官对射线过于敏感，而肿瘤本身对射线抵抗，仅应用于减少盆腔等部位复发转移所致的疼痛或不适。多种化疗方案被试用于残留、复发的以及转移的GIST，但不论是阿霉索、异环磷酰胺、丝裂霉素、氮希咪胺、足叶乙甙、顺铂及其他细胞毒药物单药还是联合化疗，客观有效率均〈7％。目前未发现单药有效率超过10％的药物，所以不主张化学治疗GIST。对于局限在腹膜的病人术后加用腹腔内化疗，仅适用于对格列卫耐药的病人。     

胃肠道间质瘤的临床研究

目的探讨胃肠道间质瘤（GIST）临床病理特点、手术治疗及预后。方法对1997年4月至2008年6月间84例手术切除的GIST患者的临床病理资料进行回顾性分析,并评价预后。结果84例GIST位于胃42例,小肠24例,食管5例,直肠6例,胃肠道外7例;肿瘤直径（5．6±4．8）cm,肿瘤组织免疫组织化学检测CD117阳性表达率为96．4％。79例行肿瘤完全切除,5例行姑息切除或肿瘤活检。78例获随访患者1、3、5年生存率分别为92．0％、79．2％和72．0％,根据肿瘤直径和核分裂像计数分级的Fletcher恶性程度风险分级与生存率有密切关系（P〈0．01）,极低度风险组、低度风险组生存率与高度风险组生存率间差异有统计学意义（P值分别为0．003及0．000）。结论GIST的Fletcher分级与患者术后生存率有关。对高度风险者,需积极施行切除范围较大的手术。     

Laparoscopic resection of gastrointestinal stromal tumors

BACKGROUND: Laparoscopic resection has become an accepted approach to gastrointestinal stromal tumors (GISTs), with acceptable early results published in the literature. Long-term recurrence rates, however, are still unclear, and the management of tumors in challenging locations requires exploration. METHODS: A retrospective analysis of all patients undergoing a laparoscopic resection of gastric GIST in our institution between November 1997 and July 2004 was performed. RESULTS: A total of 14 patients with 15 tumors were evaluated, 5 of which were located high on the lesser curve. All the patients had an attempted laparoscopic approach, with the following procedures performed: stapled wedge excision (n = 8), excision and manual sewing technique (n = 4), and distal gastrectomy (n = 1). Overall, there was a 15% (n = 2) conversion rate. Lesions found in the fundus and greater curvature areas were easily resected via simple stapled wedge excision. High lesser curve tumors were more difficult to manage and required a combination of methods for complete excision and preservation of the gastrointestinal junction including intraoperative gastroscopy, excision and manual sewing technique, and reconstruction over an esophageal bougie. There were no postoperative complications, and the length of hospital stay was 4.6 +/- 1.9 days. At a median follow-up period of 46.5 months (mean, 37.4 +/- 26 months), one patient experienced a recurrence (18 months postoperatively), with eventual disease-related death. CONCLUSION: The laparoscopic approach to gastric GIST tumors is safe and associated with acceptable short- and intermediate-term results. High lesser curve GISTs can be safely approached laparoscopically using various techniques to ensure an adequate resection margin without compromise of the GE junction.