90例中老年小腸間質瘤臨床分析

90例中老年小腸間質瘤臨床分析

羅振國周逸嬋徐偉邵耘

目的分析中老年小腸間質瘤(small intestinal stromal tumor,SIST)的臨床病理特征,為臨床診治提供經驗。方法回顧性分析2010年1月至2016年10月南京醫科大學第一附屬醫院收治的90例原發完全切除的中老年SIST病人的臨床病理特征及術后隨訪資料。結果納入90例SIST病人中,男53例(58.9%),女37例(41.1%),平均年齡(61.41±9.68)歲。腫瘤平均直徑(5.72±3.05)cm,其中位于十二指腸36例(40.0%),空腸41例(45.6%),回腸13例(14.4%)。最常見的臨床癥狀是消化道出血,共51例(56.7%)。危險度評估中,高度危險性33例(36.7%),中度危險性16例(17.6%),低度及極低度危險性33例(36.7%)。所有SIST病人接受完全切除手術,術后隨訪中,12例出現腫瘤復發,隨訪過程中無病人死亡。所有病人1年無復發生存率(relapse-free survival,RFS)為98.9%,3年RFS為95.7%,5年RFS為77.6%。結論SIST好發于中老年人,臨床表現各異,核分裂象、危險度是影響本組病人無復發生存的獨立危險因素。

小腸間質瘤; 中老年; 臨床特征

胃腸道間質瘤(gastrointestinal stromal tumors,GIST)是消化道最常見的間葉源性腫瘤,約占胃腸道腫瘤的0.1%～3%。GIST可發生在全消化道,以胃和小腸多見,食管、結直腸、網膜等部位少見[1]。小腸是GIST好發部位,但因起病隱匿,臨床表現無特異性,且檢查困難,易耽誤病情。研究顯示,小腸間質瘤(SIST)預后比原發胃間質瘤差[2],而目前關于中老年SIST缺乏大樣本多中心的研究。本研究對南京醫科大學第一附屬醫院收治的中老年SIST病人的臨床資料進行回顧性分析,以加深對中老年SIST的認識。

1 資料及方法

1.1 研究對象 本研究納入我院2010年1月至2016年10月收治的90例中老年(≥40歲)原發完全切除的SIST病人的臨床資料,男53例,女37例;年齡41～83歲,平均(61.41±9.68)歲。

1.2 研究內容 回顧性分析全部病例的臨床特點、術后病理、免疫組化表達和隨訪資料。術后病理由兩位病理專家審閱確認,術后根據2008年美國國立衛生院(NIH)的GIST危險度分級標準進行分級。見表1。

表1 GIST危險度分級標準

1.3 術后隨訪 病人出院后行電話或門診隨訪,隨訪起始時間為手術日期,終點事件定義為腫瘤復發或隨訪結束，共隨訪90例,隨訪時間2～83月。無復發生存時間定義為手術之日至腫瘤復發或隨訪結束所經歷的時間。

1.4 統計分析 采用SPSS 20.0統計學軟件進行統計分析。計量資料以均數±標準差表示。利用Kaplan-Meier法計算無復發生存率(RFS),以Log-rank檢驗進行單因素分析,具有統計學意義的變量進行Cox多因素回歸分析。P<0.05為差異有統計學意義。

2 結果

2.1 一般資料及臨床特點 SIST臨床癥狀不典型,最常見的臨床癥狀是消化道出血,共51例(56.7%),其次為貧血37例(41.1%),腹痛32例(35.6%),消瘦11例(12.2%),腹塊7例(7.8%),腸梗阻、血尿、穿孔各2例(2.2%)。7例(7.8%)中老年SIST病人合并有胃癌、肝癌、胰腺癌等腫瘤病史。37例貧血病人血紅蛋白為28～112 g/L,平均(68.51±24.36) g/L,其中<90 g/L者28例。

2.2 危險度評估及免疫組化表達 本組SIST中,腫瘤位于十二指腸36例(40.0%),空腸41例(45.6%),回腸13例(14.4%);腫瘤直徑0.6～17 cm,平均直徑(5.72±3.05) cm;腫瘤破裂1例;高度危險性33例(36.7%),中度危險性16例(17.6%),低度及極低度危險性33例(36.7%)。免疫組化檢測中,CD117及DOG-1陽性各89例(98.9%),CD34陽性42例(47.8%)。

2.3 隨訪 術后隨訪90例,隨訪過程中無病人死亡。所有病人1年RFS為98.9%, 3年RFS為95.7%,5年RFS為77.6%。單因素預后分析顯示,腫瘤直徑、部位、核分裂象、危險度與病人術后5年無復發生存相關。見表2。COX多因素分析預后分析表明,核分裂象、危險度是影響病人無復發生存的獨立危險因素(HR=6.733,95%CI:2.062～21.989,P=0.002;HR=7.220,95%CI:1.554～33.543,P=0.012)。

表2 SIST復發的單因素分析

3 討論

SIST約占GIST的20%～30%,是原發性小腸腫瘤的常見病理類型。SIST好發于中老年人,男性多見,以空腸及十二指腸為好發部位[3]。本研究SIST平均直徑5.72 cm,小于國外報道的平均直徑[4],考慮與近年來影像學及內鏡檢查技術進步,檢出率增高有關。SIST的臨床表現各異,主要與腫瘤位置、大小、性質有關,最常見的癥狀為消化道出血,據報道,大約23%～33%的GIST首發癥狀為消化道出血,主要表現為糞便潛血、黑糞、便血、嘔血[5]。本組資料中,56.7%的SIST病人因消化道出血就診,高于既往報道,可能與病人重視程度逐漸提高及SIST特點有關,對于不明原因消化道出血應排查SIST。SIST所致消化道出血引起的貧血往往較嚴重,本研究37例貧血病人中,中度以上貧血占75.7%(28例),與國外研究相符[6]。因臨床癥狀缺乏特異性,且部分病人無癥狀,SIST的早期診斷依賴于影像學檢查、膠囊內鏡、小腸鏡等手段,但早期診斷仍有困難。本研究中,7%的SIST合并其他惡性腫瘤,以消化道腫瘤多見,低于歐美文獻報道[7]。

SIST起源于小腸Cajal間質細胞,依靠病理及免疫組化確診。C-Kit和血小板源性生長因子受體α(platelet-derived growth factor receptor alpha,PDGRFA)突變在間質瘤發生發展中起重要作用[8]。研究表明,c-Kit基因表達的CD117在GIST中表達率高達90%～95%[9],本組資料中CD117陽性率為98.9%,提示CD117對GIST具有較好的診斷敏感性。CD34作為早期應用于GIST診斷的標志物,本研究中陽性率僅為47.8%,遠低于CD117。DOG-1是近年發現的鈣調控的氯離子通道蛋白,Xu等[10]研究發現DOG-1和CD117對GIST的診斷敏感性相似。值得注意的是,約5%～10%的GIST中CD117無表達,且CD117在黑色素瘤、血管肉瘤、肌纖維母細胞瘤等腫瘤中亦有表達,所以聯合DOG-1及CD34等標記物有利于提高診斷準確率。

SIST主要治療方法為手術切除,但完全切除后仍有復發可能[11],本研究中12例SIST病人出現術后復發。GIST的改良NIH危險度分級標準將腫瘤位置、大小、核分裂象以及腫瘤是否破裂作為GIST的獨立預后參數[12]。國內研究亦報道,上述參數是老年GIST預后的獨立影響因素[13]。本研究中,腫瘤大小、部位、核分裂象、危險度分級與RFS相關,且核分裂象與危險度分級是SIST預后的獨立危險因素,與既往研究結果基本一致[14]。有報道指出，伴有消化道出血的GIST預后更差[15],本研究結果顯示,消化道出血與預后無關,可能SIST與GIST預后尚存在差異。

本研究尚有許多不足:(1)部分SIST病人無癥狀,本研究所納入的人群不能完全代替整體。(2)樣本量小,且為單中心研究,還需要多中心大樣本研究進一步證實。

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Clinicalanalysisofninetycasesofmiddle-agedandelderlypatientswithsmallintestinalstromaltumors

LUOZhen-guo.

DepartmentofGeriatrics,theFirstPeople’sHospitalofChangzhou,Changzhou213003,China；

ZHOUYi-chan,XUWei,SHAOYun.

DepartmentofGeriatricGastroenterology,theFirstAffiliatedHospitalofNanjingMedicalUniversity,Nanjing210029,China

ObjectiveTo analyze the clinicopathological features of primary small intestine stromal tumors(SIST) so as to provide experience for clinical diagnosis and treatment.MethodsThe clinicopathological features of 90 patients with primary SIST, which had been completely removed, were analyzed retrospectively from January 2010 to October 2016 in the First Affiliated Hospital of Nanjing Medical University.ResultsThere were 53 males and 37 females among the 90 patients with SIST, with an average age of 61.41 ± 9.68 years. The average diameter of the tumor was 5.72 ± 3.05 cm. Among them, 36 cases (40.0%) were located in duodenum, 41 cases (45.6%) in jejunum and 13 cases (14.4%) in ileum. The most common clinical symptoms were gastrointestinal bleeding, with a total of 51 cases (56.7%). There were 33 cases (36.7%) with high risk, 16 cases (17.6%) with moderate risk, 33 cases (36.7%) with low and extremely low risk of the 90 patients. All patients with SIST underwent complete resection, and 12 patients relapsed, and no patients died during the follow-up. All patients had a 1-year relapse-free survival (RFS) of 98.9%, a 3-year RFS of 95.7% and a 5-year RFS of 76.6%. Univariate prognostic analysis showed that tumor diameter (P=0.008), location (P=0.018), mitosis (P<0.001) and NIH risk grade (P=0.003) were associated with postoperative RFS. COX multivariate analysis showed that mitosis and NIH risk grade were independent risk factors of SIST (HR=6.733, 95%CI: 2.062-21.989,P=0.002;RR=7.220, 95%CI: 1.554-33.543,P=0.012).ConclusionsNuclear mitotic and NIH risk grade are independent risk factors of the prognosis.

small intestinal stromal tumor; middle-aged and aged; clinical characteristic

江蘇省自然科學基金(BK20151038)

213003 江蘇省常州市,常州市第一人民醫院干部一科(羅振國);210029 江蘇省南京市,南京醫科大學第一附屬醫院老年消化科(周逸嬋,徐偉,邵耘)

徐偉,Email: xw2000mail@njmu.edu.cn

R 735.32

A

10.3969/j.issn.1003-9198.2017.12.008

2017-06-12)