【作者】 龚勋；

【导师】 陈宗祐； 孙鹏； 项建斌；

【作者基本信息】 复旦大学 ， 临床医学， 2008， 硕士

【摘要】 背景:胃肠间质瘤(Gastrointestinal Stromal Tumor,GIST)是消化道内少见的肿瘤,占全部胃肠道肿瘤的1～3%,却是间质肿瘤中最常见的。从1983年Mazur等第一次将GIST从平滑肌瘤及平滑肌肉瘤中区别开,到1998年Hirota等发现c-kit基因获得性突变是GIST的本质特征,再到2002年伊马替尼作为第一个分子靶向治疗肿瘤的药物在临床的广泛使用,我们对GIST的认识和治疗在25年中有了飞速的发展。但是,早期症状不典型及术后易复发仍然是困扰广大外科医生的难题。同时,影响GIST的预后因素也因研究者的不同而存在不少差异。目的:对复旦大学附属华山医院1999年—2006年间于我院住院治疗,并行手术经病理证实为胃肠间质瘤(GIST)的患者进行回顾性研究,探讨胃肠间质瘤的临床特点,手术疗效及影响预后的因素,协助临床治疗。方法:选取1999年11月—2006年12月于复旦大学附属华山医院住院手术治疗并经病理确诊为胃肠间质瘤的病例,进行电话和随访信随访。比较性别,年龄,起病症状,肿瘤部位,手术方式,术前有无转移,淋巴结清扫,免疫病理学标志及Flecther分级等对预后的影响。统计分析采用SPSS13.0软件处理,对单因素采用Kaplan-Meier法绘制生存曲线,Log-Rank法检验组间差异。多因素分析采用Cox模型分析,所有数据分析结果以p＜0.05认为具有统计学差异。结果:一、临床特点:本组确诊为GIST患者共105例,其中男性49.5%(52/105),女性50.5%(53/105)。发病年龄20～83岁,平均55.84±14.37岁。首发症状为消化道出血症状者(包括呕血、黑便、贫血)占31.4%(33/105),腹胀不适者占23.8%(25/105),腹痛者占15.2%(16/105),无意中发现或体检时发现者占29.5%(31/105)。肿瘤部位胃53.3%(56/105),小肠28.57%(30/105),结直肠11.43%(12/105),后腹膜6.67%(7/105)。瘤体长径0.5～30cm不等,平均7.04±5.24cm。根据肿瘤大小及核分裂象进行Flecther分级,其中极低风险组9.53%(10/105),低风险组33.33%(15/105),中度风险组23.81%(25/105),高风险组33.33%(35/105)。二、病理特点:GIST细胞形态以梭形细胞为主、上皮样细胞为主或二者混合。所有患者均检测CD117及CD34,其中CD117阳性占83.8%(88/105),CD34阳性占80%(84/105);部分患者检测S-100及p53。三、外科手术治疗:所有105例患者均接受了手术,其中行根治手术者86例,姑息性切除者19例。行根治手术患者中13例行联合脏器切除,包括脾、门静脉、子宫+双侧附件及whipple术等。21例患者行淋巴结清扫,共清扫林巴结111枚,均无转移。四、随访及结果分析:采用电话及随访信随访,其中失访20人,完成随访85人,随访率80.95%。随访结束时间为2007年10月。随访结果包括生存(删失)及死亡。对85位完成随访的患者的单因素生存分析显示:肿瘤部位、手术方式、术前有无转移、Fletcher分级是影响预后的因素。对多变量的Cox回归分析显示,术前有无转移是影响预后的独立因素(P=0.020),而Fletcher分级也可能是预示预后的因素之一(P=0.072)。结论:1、手术完整切除是GIST治疗的重要手段。2、首诊有无转移是影响总体生存率的独立因素。3、Fletcher分级是临床判断预后的简单有效的方法。4、伊马替尼可以显著延长肿瘤无法切除患者的生存时间,但确切疗效还需大样本临床研究。更多还原

【Abstract】 Background:Gastrointestinal stromal tumors(GISTs),a kind of rare tumor,take 1～3%of all tumors in digestive tract,but represent the most common mesenchymal tumor of the digestive tract.Since 1983,when Mazur and his colleagues distinguished GISTs from leiomyoma and leiomyosarcoma for the first time,our understanding of GISTs have dramatically improved as Hirota found the acquired mutation of c-kit,which is now thought to be the basic character of GISTs.Imatinib has been considered as a new effective treatment for GISTs since 2002.But GIST still troubled surgeons because it is lack of typical symptom and recurrence is very common.Besides,there is no consensus of risk factors because different researchers have different results.Objective:To investigate the clinical characters,surgical management and prognosis factors of patients diagnosed as GIST from 1999 to 2006 in Huashan Hospital.Method:Collect all cases of operated GISTs with pathological evidence between November 1999 and December 2006 and follow up by telephone and letters.Gender, age,clinical manifestations,locations of tumors,surgical method,lymphadenectomy, immunophenotype,and Fletcher classification are analyzed to identify factors that predict survival rate.All data were analyzed by SPSS13.0.Survival curve was drawed by Kaplan-Meier method.The univariate analysis was done by Log-Rank test and multivariate analysis was done by Cox regression.The level of significance was set at P＜0.05.Results:1.Clinical Features:All 105 cases were diagnosed as GIST,with 49.5%male and 50.5%female.Age ranged from 20～83.31.4%patients presented bleeding of alimentary tract(including haematemesis,melena and anemia),while 24.8%presented abdominal distention or indisposition,14.3%abdominal pain and 29.5%were detected only by physical or assistant examination.The locations of tumors:stomach 53.3%,small intestine 28.57%,colon and rectum 11.43%,post-peritonium 6.67%.Tumor size ranged from 0.5～30cm,with an average of 7.04cm.According to Fletcher classification,Patients were classified as following:very low risk 9.53%,low risk 33.33%,intermediate risk 23.81%,high risk 33.33%。2.Pathological Features:GISTs mainly presented as spindle cells,epithelioid cells or mixture of above the two.In all cases,CD117 and CD34 had been detected.83.8%(88/105) were positive in CD117 and 80%(84/105) were positive in CD34.S-100 and p53 were partially detected.3.Surgical Management:All 105 patients underwent operation.86 underwent radical resection and 19 underwent partial resection.21 patients underwent lymphadenectomy and no metastasis was found in all 111 lymph nodes.4.Follow-up and Results:Follow-up was done by both telephone and letters.85 patients finished the follow-up and 20 were defaulting.The status of patients was recorded as alive or dead. The follow-up ended in November 2007.The univariate analysis showed that locations of tumors,preoperative metastasis, operation type,Fletcher classification predicted a poor prognosis,while multivariate analysis showed preoperative metastasis was the only independent factor that predicted a poor prognosis(P=0.020) and Fletcher classification also might be an indicator though there is no statistical significance(P=0.072) in this research.Conclusion:1.Radical resection is still an important management for GISTs.2.Preoperative metastasis is an independent factor that predicts a poor prognosis.3.Fletcher Classification may be a simple and effective method to predict the prognosis of GISTs.4.Imatinib significantly prolongs life span in recurrence cases,but the results should be confirmed by further studies.更多还原