方 碩 詹 成 張 毅 姚光宇 謝曉楓 張永星△ 范 虹

(1復(fù)旦大學(xué)附屬中山醫(yī)院胸外科,2病理科 上海 20032)

131例縱隔原發(fā)性神經(jīng)源性腫瘤手術(shù)治療的臨床經(jīng)驗(yàn)分析

方 碩1詹 成1張 毅1姚光宇1謝曉楓2張永星1△范 虹1

(1復(fù)旦大學(xué)附屬中山醫(yī)院胸外科,2病理科 上海 20032)

目的 分析縱隔原發(fā)性神經(jīng)源性腫瘤行手術(shù)治療患者的臨床特征、治療方法和預(yù)后情況。方法 回顧性分析復(fù)旦大學(xué)附屬中山醫(yī)院胸外科2008年1月至2014年12月期間已行手術(shù)且病理證實(shí)為縱隔原發(fā)性神經(jīng)源性腫瘤共131例患者的臨床資料,包括臨床特征、影像學(xué)表現(xiàn)、手術(shù)方式、病理學(xué)形態(tài)和預(yù)后。結(jié)果 131例患者中男性78例(59.5%),女性53例(40.5%);有癥狀者59例(45.0%),無(wú)癥狀者72例(55.0%);腫瘤位于左后縱隔61例,右后縱隔69例,前縱隔1例。電視輔助胸腔鏡手術(shù)(video-assisted thoracic surgery,VATS)98例(74.8%),VATS輔助胸部小切口手術(shù)5例(3.8%),開(kāi)胸手術(shù)28例(21.4%)。除1例惡性神經(jīng)鞘瘤行姑息性切除外,其他均完整切除,無(wú)圍手術(shù)期死亡。病理類(lèi)型顯示良性神經(jīng)鞘瘤98例(74.8%),神經(jīng)節(jié)細(xì)胞瘤24例(18.3%),惡性神經(jīng)鞘瘤2例(1.5%),神經(jīng)纖維瘤2例(1.5%),副神經(jīng)節(jié)瘤2例(1.5%),原始神經(jīng)外胚層腫瘤(primitive neurotodermal tumour,PNET)2例(1.5%),神經(jīng)母細(xì)胞瘤1例(0.8%)。術(shù)后隨訪12～95個(gè)月,平均53個(gè)月,1例PNET因腫瘤廣泛轉(zhuǎn)移死亡,1例惡鞘姑息切除術(shù)后20天死亡,2例因其他原因死亡,其余均無(wú)瘤存活至2016年1月。結(jié)論 縱隔神經(jīng)源性腫瘤多無(wú)特異性臨床癥狀,絕大部分為良性,手術(shù)切除預(yù)后良好,但惡性腫瘤則預(yù)后較差。

縱隔腫瘤; 神經(jīng)源性腫瘤; 臨床特征; 手術(shù)治療; 預(yù)后

神經(jīng)源性腫瘤是縱隔最常見(jiàn)的腫瘤之一,占全部縱隔腫瘤的10.0%～34.0%[1,2],上海市胸科醫(yī)院1957—1999年間共行縱隔腫瘤手術(shù)2 638例,其中神經(jīng)源性腫瘤499例(18.9%)[3]。其分類(lèi)較為復(fù)雜,病理類(lèi)型與年齡相關(guān),解剖關(guān)系多變,治療方法不盡相同[4],本文通過(guò)對(duì)縱隔神經(jīng)源性腫瘤的分類(lèi)、臨床表現(xiàn)、輔助檢查、治療方法和結(jié)果及預(yù)后等進(jìn)行分析和總結(jié),以期為臨床診斷和個(gè)體化治療提供參考價(jià)值。

資 料 和 方 法

復(fù)旦大學(xué)附屬中山醫(yī)院胸外科2004年至2014年間行縱隔腫瘤手術(shù)患者共計(jì)2 467例,其中神經(jīng)源性腫瘤253例(10.3%)。對(duì)2008年1月至2014年12月期間由本院胸外科行手術(shù)且病理證實(shí)為縱隔原發(fā)性神經(jīng)源性腫瘤共131例患者的臨床資料進(jìn)行統(tǒng)計(jì)分析,總結(jié)患者的一般情況、臨床表現(xiàn)、輔助檢查、手術(shù)方法和結(jié)果及疾病預(yù)后情況,術(shù)后隨訪12～95個(gè)月,平均隨訪53個(gè)月。神經(jīng)源性腫瘤病理類(lèi)型較為復(fù)雜,與年齡關(guān)系密切,根據(jù)神經(jīng)細(xì)胞的胚胎發(fā)生可分為3類(lèi)[5],本研究入選患者的縱隔原發(fā)性神經(jīng)源性腫瘤分類(lèi)如表1所示。

表1 131例患者神經(jīng)源性腫瘤分類(lèi)Tab 1 Classifications of primary neurogenic tumors in 131 case

結(jié) 果

一般情況 131例患者中男性78例,女性53例,年齡15～76歲,中位年齡46歲;病理類(lèi)型顯示良性神經(jīng)鞘瘤98例(74.8%),神經(jīng)節(jié)細(xì)胞瘤24例(18.3%),惡性神經(jīng)鞘瘤、神經(jīng)纖維瘤、副神經(jīng)節(jié)瘤、原始神經(jīng)外胚層腫瘤(primitive neurotodermal tumor,PENT)各2例(1.5%),神經(jīng)母細(xì)胞瘤1例(0.8%)。其中良性腫瘤126例,惡性腫瘤5例。

臨床表現(xiàn) 多數(shù)患者無(wú)明顯癥狀(72例,55.0%),發(fā)生胸痛、胸悶、咳嗽、咳痰、上肢麻木、眼瞼下垂、面部無(wú)汗等有癥狀者59例(45.0%),其中由腫瘤而非肺部感染、心臟病等其他疾病引起的直接相關(guān)癥狀者34例(26.0%),包括胸背疼痛不適11例,胸悶5例,面部無(wú)汗4例,眼瞼下垂3例,上肢發(fā)麻刺痛3例、肩胛區(qū)酸脹不適2例,咳嗽咳痰2例,進(jìn)食梗阻2例,上肢無(wú)汗1例,上肢肌肉萎縮1例,活動(dòng)后氣促1例,口唇麻木1例,血壓升高1例。

輔助檢查 CT影像學(xué)檢查結(jié)果顯示原發(fā)灶位置情況:左側(cè)縱隔61例(左上縱隔27例,左后縱隔34例,左前縱隔1例),右側(cè)縱隔69例(右上縱隔32例,右后縱隔37例),前縱隔1例。腫瘤最小1 cm×0.5 cm×0.7 cm,最大18 cm×15 cm×4.5 cm。

手術(shù)方法和結(jié)果 電視輔助胸腔鏡手術(shù)(video-assisted thoracic surgery,VATS)手術(shù)98例(74.8%),VATS輔助胸部小切口入路5例(3.8%),開(kāi)胸手術(shù)28例(21.4%),其中右后外側(cè)切口入路9例(6.9%),左后外側(cè)切口入路7例(5.3%),VATS中轉(zhuǎn)開(kāi)胸5例(3.8%),胸部正中劈開(kāi)入路2例(1.5%),VATS輔助胸骨正中劈開(kāi)和右外側(cè)切口入路、VATS和脊柱旁后入路、脊柱旁后入路、頸切口入路、鎖骨上和左外側(cè)切口入路各1例(0.8%)。涉及VATS手術(shù)共計(jì)110例,其中側(cè)臥位98例,側(cè)俯臥位12例。有2例為啞鈴型腫瘤,其中1例女性患者(16歲)因發(fā)熱咳嗽CT檢查發(fā)現(xiàn)右下后縱隔處見(jiàn)9.8 cm×5.0 cm軟組織團(tuán)塊(圖1),呈分葉狀,邊界清,增強(qiáng)后無(wú)明確強(qiáng)化,腫塊周?chē)琴|(zhì)無(wú)明顯破壞,腫瘤主體位于胸腔,部分深入椎間孔,Ⅰ期VATS手術(shù)切除胸腔縱隔內(nèi)腫瘤。術(shù)后病理顯示為節(jié)細(xì)胞神經(jīng)瘤(圖2)。12天后行Ⅱ期脊柱旁入路,術(shù)中見(jiàn)腫瘤基底與T10～T11椎間孔及肋間神經(jīng)聯(lián)系緊密,切除T10～T11關(guān)節(jié)突,顯露椎間孔,在肉眼可及范圍切除腫瘤,植入椎弓根螺釘固定,植骨。15個(gè)月后取出脊柱內(nèi)固定。3次手術(shù)均預(yù)后良好。

圖1 1例女性患者(16歲)術(shù)前胸部CTFig 1 Preoperative chest CT of a female patient (16 y)

Separated ganglion cells stained by HE were in fascicular neuro spindle.

女性患者,57歲,增強(qiáng)CT如圖3所示,左后下縱隔占位,緊貼胸主動(dòng)脈及胸椎邊緣,邊界光整,約6.0 cm×5.5 cm,神經(jīng)鞘瘤與主動(dòng)脈外膜關(guān)系密切。術(shù)中探查見(jiàn)腫塊位于膈肌上方的左后縱隔內(nèi),約8 cm×6 cm×4 cm,與主動(dòng)脈外膜關(guān)系密切且向右側(cè)壓迫主動(dòng)脈。自主動(dòng)脈發(fā)出兩支粗短滋養(yǎng)動(dòng)脈長(zhǎng)入腫瘤。于滋養(yǎng)動(dòng)脈根部緊貼主動(dòng)脈以10 mm Hem-o-lock夾閉血管后切斷。術(shù)后發(fā)生夾閉處主動(dòng)脈狹窄,二次手術(shù)剪斷Hem-o-lock,滋養(yǎng)血管回縮形成降主動(dòng)脈破口,縫合破口,解除阻斷。術(shù)后出現(xiàn)腎功能衰竭、貧血、活動(dòng)性出血,予透析治療后好轉(zhuǎn)。術(shù)后石蠟病理切片HE染色顯示為神經(jīng)鞘瘤(圖4)。

圖3 1例女性患者(57歲)術(shù)前胸部CTFig 3 Preoperative chest CT of a female patient (57 y)

131例患者中完整切除腫瘤130例,1例姑息性切除患者為女性,54歲,腫瘤生長(zhǎng)廣泛,CT示后縱隔見(jiàn)約7.5 cm×15 cm形態(tài)不規(guī)則的團(tuán)塊影(圖5),增強(qiáng)后病灶不均勻強(qiáng)化,病灶與食管關(guān)系密切,與左心房及胃底部胃壁分界不清,部分包繞降主動(dòng)脈。術(shù)中冰凍示間葉組織來(lái)源惡性腫瘤,與左下肺、主動(dòng)脈、食管、下腔靜脈、心包界限不清,通過(guò)食管裂孔深入腹腔,無(wú)法完整切除,VATS下姑息性切除,術(shù)后20天因多臟器衰竭死亡。術(shù)后石蠟病理切片HE染色顯示為惡性神經(jīng)鞘瘤(圖6)。

疾病預(yù)后術(shù)后隨訪12～95個(gè)月,平均隨訪時(shí)間53個(gè)月,20例失訪,隨訪完成率85%,術(shù)后發(fā)生切口或胸部疼痛7例,在由腫瘤而非肺部感染、心臟病等其他疾病引起的直接相關(guān)癥狀者34例患者中,胸背疼痛不適改善5例,上肢發(fā)麻刺痛改善3例,眼瞼下垂、面部無(wú)汗、肩胛區(qū)酸脹不適、活動(dòng)后氣促改善各1例,進(jìn)食梗阻解除1例,咳嗽咳痰、胸悶消失各1 例,血壓恢復(fù)正常1 例。1例惡性神經(jīng)鞘瘤患者手術(shù)時(shí)已發(fā)生廣泛轉(zhuǎn)移術(shù)后20天死亡,1例術(shù)后2年半因罹患胰腺癌死亡,1例術(shù)后3年因腦梗死亡,1例PENT患者術(shù)后復(fù)發(fā),轉(zhuǎn)移至肺、胸膜、縱隔淋巴結(jié)、膈肌、肝,3年后死亡,另外1例PENT患者失訪。

A:The upper right corner shows schwann tumor cells and the left bottom corner shows specific lymphocyte sheath of schwanomas (HE,40×);B:Spindle tumor cells arranged in fascicular structure,which showed Antoni A zone and Antoni B zone with mucoid degerenation (HE,100×).

圖5 1例女性患者(54歲)術(shù)前胸部CTFig 5 Preoperative chest CT of a female patient (54 y)

Rich tumor cells presented fishbone like structure or arranged in whorled and storiform patternwith cell atypia(HE staining,40×).

討 論

縱隔神經(jīng)源性腫瘤包括神經(jīng)鞘源性腫瘤、自主神經(jīng)節(jié)源腫瘤、自主神經(jīng)副神經(jīng)節(jié)細(xì)胞瘤和周?chē)窠?jīng)外胚葉瘤,發(fā)生于后縱隔者約占90%～95%[6-7],本組只有1例位于前縱隔,其他均位于后縱隔,除惡性神經(jīng)鞘瘤、神經(jīng)母細(xì)胞瘤、PENT為惡性腫瘤外其他均為良性腫瘤,惡性多見(jiàn)于兒童和老年患者[8]。常缺乏特異性臨床表現(xiàn),多于體檢時(shí)發(fā)現(xiàn)(本組72例中占55.0%)。本組中25例患者因感冒、肺部感染、心臟病等其他疾病進(jìn)行影像檢查時(shí)偶然發(fā)現(xiàn)神經(jīng)源性腫瘤,占19%,由神經(jīng)源性腫瘤直接引起非特異癥狀者34例,僅占26%。腫瘤較小時(shí)一般無(wú)癥狀,腫瘤較大或者毗鄰重要器官神經(jīng)血管等可表現(xiàn)為壓迫癥狀如胸背疼痛、霍納氏綜合癥、上肢麻木刺痛、肩胛區(qū)酸脹不適,即使良性腫瘤也會(huì)出現(xiàn)咯血甚至大量血胸[4,9]。嗜鉻性副神經(jīng)節(jié)細(xì)胞瘤可引起兒茶酚胺增多癥,本組1例患者表現(xiàn)為血壓升高。腫瘤如生長(zhǎng)于椎間孔可出現(xiàn)脊髓壓迫癥狀。診斷主要依靠CT和MRI檢查,對(duì)腫瘤的位置和形態(tài)學(xué)變化可清晰顯示。CT下良性神經(jīng)源性腫瘤通常邊緣光整,分界清晰,腫瘤長(zhǎng)期壓迫可造成瘤體周?chē)琴|(zhì)改變,如肋間隙增寬、椎體和肋骨后端出現(xiàn)壓跡或破壞,壓迫氣管可出現(xiàn)氣管縮窄,壓迫食管可出現(xiàn)食管突然扭曲,如出現(xiàn)椎間孔擴(kuò)大應(yīng)加做MRI以明確是否為啞鈴型腫瘤。

在封閉的胸腔中有很多重要器官和組織結(jié)構(gòu),即使良性縱隔腫瘤也會(huì)引起嚴(yán)重的癥狀[10],縱隔神經(jīng)源性腫瘤有繼續(xù)生長(zhǎng)增大趨勢(shì),壓迫周?chē)堋⑸窠?jīng)、食管、氣管等組織,生長(zhǎng)于椎管內(nèi)的腫瘤通常會(huì)壓迫脊髓,良性神經(jīng)源性腫瘤有潛在惡變可能性[11]。因?yàn)榇┐汤щy,術(shù)前難以獲得病理診斷,無(wú)論患者有無(wú)癥狀或者腫瘤良惡性,一經(jīng)診斷通常手術(shù)切除,術(shù)中快速冰凍可以提示腫瘤類(lèi)型和良惡性,根據(jù)腫瘤大小、部位、是否粘連、是否侵入椎管選擇VATS或開(kāi)放性手術(shù),惡性神經(jīng)鞘瘤對(duì)放化療不敏感[4],但PENT經(jīng)放化療后體積可縮小已被證明是安全有效的方法[12]。1992年,Landreneau等[13]首次報(bào)道使用胸腔鏡切除縱隔神經(jīng)鞘瘤,近年來(lái)VATS手術(shù)應(yīng)用越來(lái)越多,具有創(chuàng)傷小、暴露清晰、預(yù)后快等優(yōu)點(diǎn)[14-17],但是應(yīng)做好VATS中轉(zhuǎn)開(kāi)胸的準(zhǔn)備[18]。Daiko等[19]首次報(bào)道VATS下俯臥位行縱隔腫瘤切除術(shù),俯臥位下無(wú)需助手牽拉心肺臟器,可自然下垂,可以很好的暴露后縱隔,少量出血會(huì)積聚在胸腔下方,不會(huì)使手術(shù)野模糊。但是俯臥位下如果發(fā)生大出血或者腫瘤無(wú)法腔鏡下切除等原因需要中轉(zhuǎn)開(kāi)胸則必須再次更換手術(shù)體位,因此我們多采用側(cè)俯臥位,以便在緊急情況下中轉(zhuǎn)開(kāi)胸。對(duì)于大多數(shù)惡性腫瘤、胸腔鏡無(wú)法達(dá)到的特殊部位及腫瘤體積過(guò)大或者粘連嚴(yán)重者應(yīng)選擇開(kāi)放性手術(shù)。大多數(shù)神經(jīng)源性腫瘤有包膜,出現(xiàn)粘連或與血管關(guān)系密切應(yīng)提防大出血。啞鈴型神經(jīng)源性腫瘤的手術(shù)處理比較棘手,術(shù)前應(yīng)明確檢查,否則切除胸腔內(nèi)腫瘤時(shí)易造成椎管內(nèi)出血壓迫。手術(shù)方式多樣,根據(jù)兩端腫瘤大小、位置選擇手術(shù)入路,通常需要聯(lián)合脊柱后入路[14,20-22],對(duì)于體積較小的腫瘤采用單一前入路或單一脊柱后入路,如果腫瘤體積較大應(yīng)聯(lián)合前入路和脊柱后入路。本組2例啞鈴型腫瘤根據(jù)不同的位置大小選用了不同的手術(shù)策略。近年來(lái)已有達(dá)芬奇手術(shù)應(yīng)用于縱隔神經(jīng)源性腫瘤的安全性、可行性報(bào)道[23-24],但是價(jià)格昂貴,且需要更大群體的研究和更長(zhǎng)時(shí)間的隨訪驗(yàn)證。

綜上所述,神經(jīng)源性腫瘤是縱隔腫瘤中最常見(jiàn)的腫瘤,病理類(lèi)型多樣,在成人中最多見(jiàn)的是良性神經(jīng)鞘瘤,其次為神經(jīng)節(jié)細(xì)胞瘤,其他類(lèi)型較為罕見(jiàn);良性居多,多無(wú)特異性臨床癥狀,大多為體檢發(fā)現(xiàn);診斷主要依靠術(shù)前CT和MRI,一般位于后縱隔,位置及與周?chē)K器毗鄰關(guān)系多變,需要根據(jù)術(shù)前影像結(jié)合術(shù)中解剖制定個(gè)體化手術(shù)策略。良性腫瘤預(yù)后很好,惡性腫瘤預(yù)后較差。

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Clinical experience of primary neurogenic tumors in mediastinum with surgical treatment in 131 cases

FANG Shuo1, ZHAN Cheng1, ZHANG Yi1, YAO Guang-yu1, XIE Xiao-feng2, ZHANG Yong-xing1△, FAN Hong1

(1DepartmentofThoracicSurgery,2DepartmentofPathology,ZhongshanHospital,FudanUniversity,Shanghai200032,China)

Objective To analyze the clinical features,methods of treatment and prognosis of primary neurogenic tumors of mediastinum in patients taking surgical intervention. Methods A database was maintained retrospectively of all patients undergoing surgery for tumor and pathologically diagnosed with primary neurogenic tumors of mediastinum,managed in the Department of Thoracic Surgery,Zhongshan Hospital,Fudan University,Shanghai between Jan.,2008 and Dec.,2014.This work analyzed retrospectively the information about clinical and imaging features,surgical techniques and outcome extracted from medical records. Results Among the 131 cases,78 cases (59.5%) were males,53 cases (40.5%) were females;72 cases were diagnosed incidentally (55.0%),while the other 59 cases (45.0%) suffered from different symptoms.The posterior mediastinum was the most principal location with 61 cases in the left and 69 cases in the right,and 1 case remained in the anterior mediastinum.Total 98 cases (74.8%) underwent surgeries via video-assisted thoracic surgery (VATS),5 cases (3.8%) took VATS surgery with small incision,and 28 cases (21.4%) experienced open thoracotomy,with no mortality during perioperative period.Gross total resection was obtained in 130 patients (99.2%).The remaining patient underwent a palliative resection for malignant schwannomas.Of the patients,98 cases had benign schwannomas (74.8%),24 cases had gangliocytomas (18.3%),2 cases had malignant schwannomas (1.5%),2 cases had neurofibromas (1.5%),2 cases had paragangliomas (1.5%),2 cases hadprimitive neurotodermal tumor (PNET) (1.5%) and 1 case had neuroblastomas (0.8%).All patients were followed up from 12 to 95 months with an average of 53 months.A patient with PNET died of tumor metastasis,a patient with malignant schwannomas died after palliative ectomy,and 2 cases died of other reasons.The rest survived until Jan., 2016 with tumor free. Conclusions Nearly no specific clinical symptoms occur in neurogenic tumors of mediastinum.Most of neurogenic tumors of mediastinum are benign with optimistic prognosis after surgical treatment.While malignant neurogenic tumorsusually come with poor prognosis,which places special emphasis on early diagnose together with surgical treatment.

mediastinal neoplasms; neurogenic tumors; clinical characteristics; surgical treatment; prognosis

國(guó)家自然科學(xué)基金(81401875)

R734.5

A

10.3969/j.issn.1672-8467.2017.02.012

2016-05-25;編輯:段佳)

△Corresponding author E-mail:zhang.yongxing@zs-hospital.sh.cn

* This work was supported by the National Natural Science Foundation of China (81401875).