90例中老年小腸間質(zhì)瘤臨床分析

90例中老年小腸間質(zhì)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(zhì)瘤(small intestinal stromal tumor,SIST)的臨床病理特征,為臨床診治提供經(jīng)驗(yàn)。方法回顧性分析2010年1月至2016年10月南京醫(yī)科大學(xué)第一附屬醫(yī)院收治的90例原發(fā)完全切除的中老年SIST病人的臨床病理特征及術(shù)后隨訪資料。結(jié)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(xiǎn)度評(píng)估中,高度危險(xiǎn)性33例(36.7%),中度危險(xiǎn)性16例(17.6%),低度及極低度危險(xiǎn)性33例(36.7%)。所有SIST病人接受完全切除手術(shù),術(shù)后隨訪中,12例出現(xiàn)腫瘤復(fù)發(fā),隨訪過程中無病人死亡。所有病人1年無復(fù)發(fā)生存率(relapse-free survival,RFS)為98.9%,3年RFS為95.7%,5年RFS為77.6%。結(jié)論SIST好發(fā)于中老年人,臨床表現(xiàn)各異,核分裂象、危險(xiǎn)度是影響本組病人無復(fù)發(fā)生存的獨(dú)立危險(xiǎn)因素。

小腸間質(zhì)瘤; 中老年; 臨床特征

胃腸道間質(zhì)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(fā)生在全消化道,以胃和小腸多見,食管、結(jié)直腸、網(wǎng)膜等部位少見[1]。小腸是GIST好發(fā)部位,但因起病隱匿,臨床表現(xiàn)無特異性,且檢查困難,易耽誤病情。研究顯示,小腸間質(zhì)瘤(SIST)預(yù)后比原發(fā)胃間質(zhì)瘤差[2],而目前關(guān)于中老年SIST缺乏大樣本多中心的研究。本研究對(duì)南京醫(yī)科大學(xué)第一附屬醫(yī)院收治的中老年SIST病人的臨床資料進(jìn)行回顧性分析,以加深對(duì)中老年SIST的認(rèn)識(shí)。

1 資料及方法

1.1 研究對(duì)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(fā)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?jī)?nèi)容 回顧性分析全部病例的臨床特點(diǎn)、術(shù)后病理、免疫組化表達(dá)和隨訪資料。術(shù)后病理由兩位病理專家審閱確認(rèn),術(shù)后根據(jù)2008年美國國立衛(wèi)生院(NIH)的GIST危險(xiǎn)度分級(jí)標(biāo)準(zhǔn)進(jìn)行分級(jí)。見表1。

表1 GIST危險(xiǎn)度分級(jí)標(biāo)準(zhǔn)

1.3 術(shù)后隨訪 病人出院后行電話或門診隨訪,隨訪起始時(shí)間為手術(shù)日期,終點(diǎn)事件定義為腫瘤復(fù)發(fā)或隨訪結(jié)束，共隨訪90例,隨訪時(shí)間2～83月。無復(fù)發(fā)生存時(shí)間定義為手術(shù)之日至腫瘤復(fù)發(fā)或隨訪結(jié)束所經(jīng)歷的時(shí)間。

1.4 統(tǒng)計(jì)分析 采用SPSS 20.0統(tǒng)計(jì)學(xué)軟件進(jìn)行統(tǒng)計(jì)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示。利用Kaplan-Meier法計(jì)算無復(fù)發(fā)生存率(RFS),以Log-rank檢驗(yàn)進(jìn)行單因素分析,具有統(tǒng)計(jì)學(xué)意義的變量進(jìn)行Cox多因素回歸分析。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 一般資料及臨床特點(diǎn) 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(xiǎn)度評(píng)估及免疫組化表達(dá) 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(xiǎn)性33例(36.7%),中度危險(xiǎn)性16例(17.6%),低度及極低度危險(xiǎn)性33例(36.7%)。免疫組化檢測(cè)中,CD117及DOG-1陽性各89例(98.9%),CD34陽性42例(47.8%)。

2.3 隨訪 術(shù)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(yù)后分析顯示,腫瘤直徑、部位、核分裂象、危險(xiǎn)度與病人術(shù)后5年無復(fù)發(fā)生存相關(guān)。見表2。COX多因素分析預(yù)后分析表明,核分裂象、危險(xiǎn)度是影響病人無復(fù)發(fā)生存的獨(dú)立危險(xiǎn)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(fù)發(fā)的單因素分析

3 討論

SIST約占GIST的20%～30%,是原發(fā)性小腸腫瘤的常見病理類型。SIST好發(fā)于中老年人,男性多見,以空腸及十二指腸為好發(fā)部位[3]。本研究SIST平均直徑5.72 cm,小于國外報(bào)道的平均直徑[4],考慮與近年來影像學(xué)及內(nèi)鏡檢查技術(shù)進(jìn)步,檢出率增高有關(guān)。SIST的臨床表現(xiàn)各異,主要與腫瘤位置、大小、性質(zhì)有關(guān),最常見的癥狀為消化道出血,據(jù)報(bào)道,大約23%～33%的GIST首發(fā)癥狀為消化道出血,主要表現(xiàn)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(bào)道,可能與病人重視程度逐漸提高及SIST特點(diǎn)有關(guān),對(duì)于不明原因消化道出血應(yīng)排查SIST。SIST所致消化道出血引起的貧血往往較嚴(yán)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(xué)檢查、膠囊內(nèi)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(xiàn)報(bào)道[7]。

SIST起源于小腸Cajal間質(zhì)細(xì)胞,依靠病理及免疫組化確診。C-Kit和血小板源性生長(zhǎng)因子受體α(platelet-derived growth factor receptor alpha,PDGRFA)突變?cè)陂g質(zhì)瘤發(fā)生發(fā)展中起重要作用[8]。研究表明,c-Kit基因表達(dá)的CD117在GIST中表達(dá)率高達(dá)90%～95%[9],本組資料中CD117陽性率為98.9%,提示CD117對(duì)GIST具有較好的診斷敏感性。CD34作為早期應(yīng)用于GIST診斷的標(biāo)志物,本研究中陽性率僅為47.8%,遠(yuǎn)低于CD117。DOG-1是近年發(fā)現(xiàn)的鈣調(diào)控的氯離子通道蛋白,Xu等[10]研究發(fā)現(xiàn)DOG-1和CD117對(duì)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(dá),且CD117在黑色素瘤、血管肉瘤、肌纖維母細(xì)胞瘤等腫瘤中亦有表達(dá),所以聯(lián)合DOG-1及CD34等標(biāo)記物有利于提高診斷準(zhǔn)確率。

SIST主要治療方法為手術(shù)切除,但完全切除后仍有復(fù)發(fā)可能[11],本研究中12例SIST病人出現(xiàn)術(shù)后復(fù)發(fā)。GIST的改良NIH危險(xiǎn)度分級(jí)標(biāo)準(zhǔn)將腫瘤位置、大小、核分裂象以及腫瘤是否破裂作為GIST的獨(dú)立預(yù)后參數(shù)[12]。國內(nèi)研究亦報(bào)道,上述參數(shù)是老年GIST預(yù)后的獨(dú)立影響因素[13]。本研究中,腫瘤大小、部位、核分裂象、危險(xiǎn)度分級(jí)與RFS相關(guān),且核分裂象與危險(xiǎn)度分級(jí)是SIST預(yù)后的獨(dú)立危險(xiǎn)因素,與既往研究結(jié)果基本一致[14]。有報(bào)道指出，伴有消化道出血的GIST預(yù)后更差[15],本研究結(jié)果顯示,消化道出血與預(yù)后無關(guān),可能SIST與GIST預(yù)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(jìn)一步證實(shí)。

[1] Guller U, Tarantino I, Cerny T, et al. Revisiting a dogma: similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis [J]. Gastric Cancer, 2017, 20(1):49-60.

[2] Nishida T, Blay JY, Hirota S, et al. The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines [J]. Gastric Cancer, 2016, 19(1):3-14.

[3] Xing GS, Wang S, Sun YM, et al. Small bowel stromal tumors: Different clinicopathologic and computed tomography features in various anatomic sites [J]. PLoS One, 2015, 10(12):e144277.

[4] Baheti AD, Shinagare AB, O’Neill AC, et al. MDCT and clinicopathological features of small bowel gastrointestinal stromal tumours in 102 patients: a single institute experience [J]. Br J Radiol, 2015, 88(1053):20150085.

[5] Wang M, Xu J, Zhang Y, et al. Gastrointestinal stromal tumor: 15-years’ experience in a single center [J]. BMC Surg, 2014, 14:93.

[6] Lopes LF, Ojopi EB, Bacchi CE. Gastrointestinal stromal tumor in Brazil: clinicopathology, immunohistochemistry, and molecular genetics of 513 cases [J]. Pathol Int, 2008, 58(6):344-352.

[7] Pandurengan RK, Dumont AG, Araujo DM, et al. Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor [J]. Ann Oncol, 2010, 21(10):2107-2111.

[8] Giuliano K, Nagarajan N, Canner J, et al. Gastric and small intestine gastrointestinal stromal tumors: Do outcomes differ? [J]. J Surg Oncol, 2017, 115(3):351-357.

[9] Yan W, Zhang A, Powell MJ. Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors [J]. Chin J Cancer, 2016, 35(1):68.

[10] Xu C, Han H, Wang J, et al. Diagnosis value of CD117 and PDGFRA, alone or in combination DOG1, as biomarkers for gastrointestinal stromal tumors [J]. Ann Transl Med, 2015, 3(20):308.

[11] Wang H, Chen P, Liu XX, et al. Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors [J]. World J Surg Oncol, 2014, 12:89.

[12] Koo DH, Ryu MH, Kim KM, et al. Asian consensus guidelines for the diagnosis and management of gastrointestinal stromal tumor [J]. Cancer Res Treat, 2016, 48(4):1155-1166.

[13] 喬靜靜,張保國,陳錦飛. 老年患者胃腸道間質(zhì)瘤預(yù)后因素分析[J]. 實(shí)用老年醫(yī)學(xué), 2012, 26(3):218-220.

[14] Brudvik KW, Patel SH, Roland CL, et al. Survival after resection of gastrointestinal stromal tumor and sarcoma liver metastases in 146 patients [J]. J Gastrointest Surg, 2015, 19(8):1476-1483.

[15] 李若彤,張國敬,付蔚華,等. 胃腸間質(zhì)瘤合并消化道出血的預(yù)后分析[J]. 中華腫瘤雜志, 2016, 38(5):377-380.

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(xué)基金(BK20151038)

213003 江蘇省常州市,常州市第一人民醫(yī)院干部一科(羅振國);210029 江蘇省南京市,南京醫(yī)科大學(xué)第一附屬醫(yī)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)