劉豆豆 劉亦菲 張廷杰 程木華
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·述評(píng)·
PET/CT在子宮內(nèi)膜癌中的應(yīng)用
劉豆豆劉亦菲張廷杰程木華
通訊作者簡(jiǎn)介:程木華,醫(yī)學(xué)博士,教授,主任醫(yī)師,博士生導(dǎo)師?,F(xiàn)任中山大學(xué)附屬第三醫(yī)院核醫(yī)學(xué)科主任,中山大學(xué)附屬第三醫(yī)院核醫(yī)學(xué)教研室主任,中山大學(xué)醫(yī)學(xué)影像核醫(yī)學(xué)課程負(fù)責(zé)人之一,廣東省中西醫(yī)結(jié)合學(xué)會(huì)核醫(yī)學(xué)專(zhuān)業(yè)委員會(huì)副主任委員,廣東省醫(yī)療行業(yè)協(xié)會(huì)醫(yī)學(xué)影像管理分會(huì)的副主任委員,中華醫(yī)學(xué)會(huì)核醫(yī)學(xué)分會(huì)治療學(xué)組委員,中國(guó)醫(yī)學(xué)影像技術(shù)研究會(huì)核醫(yī)學(xué)分會(huì)委員,廣東省醫(yī)學(xué)會(huì)核醫(yī)學(xué)分會(huì)常委,JNPC雜志編委,多個(gè)國(guó)內(nèi)外雜志特邀審稿專(zhuān)家。精通單光子發(fā)射計(jì)算機(jī)體層攝影術(shù)/計(jì)算機(jī)X線體層掃描(SPECT/CT)、正電子發(fā)射型計(jì)算機(jī)體層攝影術(shù)/計(jì)算機(jī)X線體層掃描(PET/CT)的各種疾病影像診斷及疑難雜癥的影像分析;擅長(zhǎng)甲狀腺系列疾病診治,尤其在甲狀腺疾病的鑒別診斷,甲狀腺癌、甲狀腺功能亢進(jìn)131I治療和皮膚血管瘤敷貼治療等方面具有豐富臨床經(jīng)驗(yàn)。主要從事分子核醫(yī)學(xué)的基礎(chǔ)及臨床研究,獲得國(guó)家自然科學(xué)基金以及參與省部科研基金等支持的多個(gè)科研課題。近5年發(fā)表學(xué)術(shù)論文60多篇,其中SCI雜志收錄論文10多篇,參編6本專(zhuān)著。1997年獲中山醫(yī)科大學(xué)醫(yī)療成果三等獎(jiǎng)1項(xiàng),2013年獲計(jì)算機(jī)軟件著作權(quán)專(zhuān)利1項(xiàng),2014年獲廣東省科技成果獎(jiǎng)三等獎(jiǎng)1項(xiàng)。
子宮內(nèi)膜癌是婦科常見(jiàn)的惡性腫瘤之一,總體預(yù)后較好,準(zhǔn)確的術(shù)前分期及評(píng)估子宮外受累風(fēng)險(xiǎn)決定了手術(shù)方式和范圍。正電子發(fā)射型計(jì)算機(jī)體層攝影術(shù)/計(jì)算機(jī)體層掃描不僅在診斷子宮內(nèi)膜癌盆腔、腹主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)處轉(zhuǎn)移及評(píng)價(jià)預(yù)后、復(fù)發(fā)診斷等方面具有其獨(dú)特的價(jià)值,而且原發(fā)灶的最大標(biāo)準(zhǔn)攝取值、腫瘤代謝總體積和病灶總糖酵解量等參數(shù)更有望作為術(shù)前評(píng)估子宮內(nèi)膜癌預(yù)后的重要無(wú)創(chuàng)性指標(biāo)。
正電子發(fā)射體層攝影術(shù);子宮內(nèi)膜癌;復(fù)發(fā);淋巴結(jié)轉(zhuǎn)移
子宮內(nèi)膜癌(EC)是女性婦科常見(jiàn)的腫瘤之一,約占女性總惡性腫瘤的7%,占女性生殖道惡性腫瘤的20%~30%[1]。美國(guó)癌癥協(xié)會(huì)最新數(shù)據(jù),2016年預(yù)計(jì)EC新發(fā)60 050例(7%)、死亡10 470例(4%),其中預(yù)計(jì)新發(fā)人數(shù)已超過(guò)宮頸癌(12 990例),是女性繼乳腺癌、肺癌、結(jié)直腸癌外的第四大惡性腫瘤,占婦科惡性腫瘤的首位[2]。在我國(guó),隨著人均壽命的延長(zhǎng)、飲食結(jié)構(gòu)的改變、節(jié)育器和性激素替代治療的應(yīng)用,EC發(fā)病率正逐年上升,2015年預(yù)計(jì)EC的發(fā)生率和死亡率分別為63.4/100 000和21.8/100 000[3]。EC臨床癥狀典型,75%患者就診時(shí)為早期,總體預(yù)后較好,Ⅰ~Ⅳ期的5年平均生存率分別為85%、70%、50%、18%,但仍有20%~25%的患者在3年內(nèi)復(fù)發(fā),合并區(qū)域盆腔淋巴結(jié)、腹主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移的EC患者生存率分別僅為57.0%、49.4%[4-5]。
EC分Ⅰ型和Ⅱ型,其中以Ⅰ型最常見(jiàn),約占90%,好發(fā)于絕經(jīng)早期,多在子宮內(nèi)膜增生的基礎(chǔ)上發(fā)生癌變,分化及預(yù)后良好;Ⅱ型為非子宮內(nèi)膜樣腺癌,包括漿液型乳頭狀癌、透明細(xì)胞癌及癌肉瘤等,好發(fā)于老年女性,預(yù)后差,較早發(fā)生轉(zhuǎn)移或浸潤(rùn)。目前按FIGO分期及組織分化程度將Ⅰ型EC分為G1~G3級(jí)(高-中-低分化),低危指Ⅰ型G1 /G2級(jí)FIGO ⅠA期,中危指Ⅰ型G1 /G2級(jí)FIGO ⅠB期或Ⅰ型G3級(jí)FIGO ⅠA期,高危指Ⅱ型G3級(jí)FIGOⅠB 或FIGO Ⅱ~ Ⅳ期[6]。EC治療首選手術(shù),術(shù)式的選擇和范圍取決于EC分期及子宮外受累的風(fēng)險(xiǎn),因此術(shù)前準(zhǔn)確地評(píng)估原發(fā)灶范圍、子宮肌層浸潤(rùn)深度、子宮頸、子宮旁受累程度、淋巴結(jié)或遠(yuǎn)處轉(zhuǎn)移情況,術(shù)后定期監(jiān)測(cè)以評(píng)估復(fù)發(fā)、轉(zhuǎn)移對(duì)手術(shù)方式的選擇及判斷預(yù)后至關(guān)重要。
與傳統(tǒng)影像學(xué)檢查相比,正電子發(fā)射型計(jì)算機(jī)體層攝影術(shù)/計(jì)算機(jī)體層掃描(PET/CT)在病變形態(tài)、解剖改變前便可發(fā)現(xiàn)代謝、功能的異常,從而可提前發(fā)現(xiàn)早期的病變。18F-氟代脫氧葡萄糖(18F-FDG)PET的主要原理是靜脈注射的葡萄糖類(lèi)似物18F-FDG,通過(guò)細(xì)胞膜上的葡萄糖轉(zhuǎn)運(yùn)體進(jìn)入細(xì)胞,被胞漿中的己糖激酶磷酸化,后者既不能被特異度的果糖-1-激酶進(jìn)一步分解,也不能去磷酸化而溢出,故而長(zhǎng)時(shí)間滯留于細(xì)胞內(nèi)。胞漿中6-磷酸-18F-FDG的量反映了組織細(xì)胞的葡萄糖代謝水平,而大部分惡性腫瘤葡萄糖高代謝特點(diǎn)使其呈18F-FDG高攝取。正常子宮體呈低代謝,絕經(jīng)前婦女的卵巢和子宮內(nèi)膜FDG攝取隨月經(jīng)周期呈生理性波動(dòng),排卵期和月經(jīng)期子宮內(nèi)膜的標(biāo)準(zhǔn)攝取值(SUV)通常高于增殖期和分泌期,而卵巢約81%FDG攝取在卵泡晚期及黃體早期增高。絕經(jīng)后婦女的子宮內(nèi)膜及卵巢攝取18F-FDG非常少,若絕經(jīng)后子宮內(nèi)膜或卵巢、附件局限性代謝增高,一般需要進(jìn)一步檢查或隨訪,而卵巢在排除良性病變前基本上考慮為惡性[7-10]。了解女性生殖系統(tǒng)在月經(jīng)周期中各階段攝取18F-FDG情況,對(duì)子宮內(nèi)膜的生理、病理性改變的鑒別至關(guān)重要。因此對(duì)于絕經(jīng)前患者,PET/CT檢查的理想時(shí)間應(yīng)是月經(jīng)周期前或后。
分段診斷刮宮和宮腔鏡檢查為術(shù)前診斷EC類(lèi)型和級(jí)別的金標(biāo)準(zhǔn),但不能判斷肌層浸潤(rùn)的深度及周?chē)址盖闆r,不能用于分期,同時(shí)分段診刮為非直視下操作,診刮組織物有限,其準(zhǔn)確度易受影響,特別是EC合并子宮內(nèi)膜不典型復(fù)雜性增生時(shí)容易漏診,因此術(shù)前需結(jié)合影像學(xué)檢查評(píng)價(jià)EC的范圍[11]。惡性腫瘤細(xì)胞增殖快,糖酵解增高,典型的EC在PET/CT上常表現(xiàn)為增厚的子宮內(nèi)膜或腫塊,18F-FDG高攝取。但是子宮內(nèi)膜增生、子宮內(nèi)膜炎、子宮內(nèi)膜息肉及宮腔積膿等良性病變也攝取18F-FDG,呈假陽(yáng)性[12]。繼發(fā)于子宮內(nèi)膜增生基礎(chǔ)上的小灶性癌變(部分ⅠA),由于PET空間分辨率較低,當(dāng)腫瘤細(xì)胞尚不足以表現(xiàn)出糖代謝改變時(shí)呈假陰性。Kakhki等[13]的薈萃分析中發(fā)現(xiàn)雖然PET/CT在診斷EC原發(fā)灶的敏感度和特異度高達(dá)81.8% (77.9%~85.3%)和89.8% (79.2%~96.2%),但是仍不推薦PET/CT作為EC篩查及原發(fā)灶初始診斷的首選影像學(xué)檢查方法。因?yàn)镸RI對(duì)EC肌層浸潤(rùn)深度的診斷準(zhǔn)確度高達(dá)90%以上,Gallego等[14]在51例EC患者的前瞻性研究中,發(fā)現(xiàn)表觀彌散系數(shù)(ADC)診斷子宮肌層浸潤(rùn)深度與術(shù)中冰凍切片的準(zhǔn)確度一致,均為90.2%,比MRI常規(guī)序列準(zhǔn)確度更高,甚至提出若術(shù)前行MRI常規(guī)序列+彌散加權(quán)成像(DWI)+ADC圖,將有望免去冰凍組織切片檢查。
子宮肌層浸潤(rùn)的深度決定EC的臨床分期,小于50%為ⅠA期,大于50%為ⅠB期,ⅠB期提示患者中-高危,大約30%ⅠB期患者發(fā)生淋巴結(jié)轉(zhuǎn)移,而淋巴結(jié)轉(zhuǎn)移是預(yù)后不良的指征。PET/CT評(píng)價(jià)肌層受累深度仍有一定的局限性,特別是ⅠA期。Antonsen等[15]分析了318例ⅠA~ⅣB EC患者PET/CT、MRI和二維超聲的表現(xiàn),同時(shí)對(duì)比了均行3種影像學(xué)檢查的133例患者診斷腫瘤浸潤(rùn)程度的情況,其中PET/CT的敏感度、特異度及準(zhǔn)確度分別88.9%、43.5%、63.9%,MRI和二維超聲相應(yīng)為88.9%、57%、66.7%和69.4%、74.4%、73.2%,PET/CT及MRI有相似的功效,二維超聲雖然敏感度相對(duì)較低,但是特異度和準(zhǔn)確度最高,PET/CT及MRI的陰性預(yù)測(cè)值均在92%以上,提示PET/CT可以篩選出無(wú)深肌層浸潤(rùn)的患者,從而避免過(guò)度手術(shù),特別是育齡期及一般情況差的患者。在宮頸侵犯方面,三者特異度和準(zhǔn)確度均較高,但是敏感度均較低。
研究表明,區(qū)域淋巴結(jié)轉(zhuǎn)移是影響EC預(yù)后的重要因素,F(xiàn)IGO建議把盆腔淋巴結(jié)轉(zhuǎn)移評(píng)為ⅢC1期,主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移評(píng)為ⅢC2期,而腹腔或腹股溝區(qū)淋巴結(jié)轉(zhuǎn)移評(píng)為Ⅳ期。對(duì)淋巴結(jié)轉(zhuǎn)移灶早期、準(zhǔn)確的判斷在EC分期上至關(guān)重要。PET/CT作為無(wú)創(chuàng)的檢查,結(jié)合病灶代謝及解剖的優(yōu)勢(shì),可在術(shù)前發(fā)現(xiàn)常規(guī)CT及MRI未能確診的、在淋巴結(jié)形態(tài)及密度改變前的5~9 mm微小淋巴結(jié)轉(zhuǎn)移灶,以及單純的腹主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移和腸系膜、腹腔等遠(yuǎn)處隱匿性的轉(zhuǎn)移灶。雖然有學(xué)者認(rèn)為,MRI在診斷淋巴結(jié)轉(zhuǎn)移上有一定的優(yōu)勢(shì),但是Park等[16]分析比較53例患者的PET/CT和MRI表現(xiàn),發(fā)現(xiàn)無(wú)論是盆腔淋巴結(jié)還是腹主動(dòng)脈旁淋巴結(jié),PET/CT均較MRI有較高的敏感度和特異度。Antosen等[15]的研究也證實(shí)PET/CT較MRI的敏感度更高(85.7% vs. 57.1%)。但是 Kitajima等[17]卻發(fā)現(xiàn)磁共振彌散加權(quán)成像(DWI)較PET/CT有較高的敏感度(83% vs. 38%),但是特異度 (51% vs. 96%) 及準(zhǔn)確度(57% vs. 86%)均較低,這可能與DWI主要反映的是細(xì)胞內(nèi)水分子擴(kuò)散有關(guān),DWI的信號(hào)受細(xì)胞密度、細(xì)胞膜完整性以及T2信號(hào)的影響,若細(xì)胞密度足夠高或者存在T2穿透效應(yīng),即使正常的淋巴結(jié)也可表現(xiàn)為高信號(hào)。Kakhki等[13]分析16篇文章,結(jié)果顯示PET/CT診斷淋巴結(jié)轉(zhuǎn)移的敏感度雖然僅有72.3%,但是特異度和準(zhǔn)確度卻高達(dá)92.9%和95%。Crivellaro等[18]比較了76例臨床Ⅰ期高危EC患者術(shù)后病理與PET/CT顯像結(jié)果,發(fā)現(xiàn)診斷淋巴結(jié)轉(zhuǎn)移的敏感度達(dá)78.6%,但是特異度和陰性預(yù)測(cè)值高達(dá)98.4%和95.3%,并且淋巴結(jié)轉(zhuǎn)移與原發(fā)灶最大標(biāo)準(zhǔn)攝取值(SUVmax)、腫瘤代謝總體積 (MTV)、病灶總糖酵解量(TLG)相關(guān)。多項(xiàng)研究均表明,PET/CT在診斷淋巴結(jié)轉(zhuǎn)移中有較高的特異度,但是敏感度相對(duì)稍低,可能是病灶攝取FDG的量受病灶葡萄糖轉(zhuǎn)運(yùn)體、己糖激酶、葡萄糖-6-磷酸酶的水平影響,只有當(dāng)病灶含有足夠的腫瘤細(xì)胞(104~107)才能使增強(qiáng)的葡萄糖代謝在PET/CT上表現(xiàn)出來(lái),而對(duì)低級(jí)別或組織學(xué)為漿液型或黏蛋白型癌的檢出率欠佳[19]。
在初始診斷時(shí),4%~6%的EC患者已經(jīng)發(fā)生遠(yuǎn)處轉(zhuǎn)移[5]。Kakhki等[13]報(bào)道,PET/CT診斷轉(zhuǎn)移灶的敏感度和特異度均在95%以上,Grisaru等[20]的研究發(fā)現(xiàn)PET/CT診斷轉(zhuǎn)移灶的準(zhǔn)確度高達(dá)100%,比同期傳統(tǒng)影像學(xué)(MRI, CT, 超聲) 多發(fā)現(xiàn)28%的病灶,這主要是因?yàn)镻ET/CT為全身顯像,其對(duì)病灶的檢出率較局部檢查更高,特別是隱匿的、非常規(guī)位置的病灶,比如網(wǎng)膜、腹盆腔外組織(鎖骨上淋巴結(jié)、縱隔淋巴結(jié)等)以及肌肉內(nèi)轉(zhuǎn)移灶,Ho等[21]和Ortas等[22]就分別報(bào)道了經(jīng)PET/CT發(fā)現(xiàn)EC右側(cè)棘突旁肌內(nèi)轉(zhuǎn)移及早期EC僅腹股溝淋巴結(jié)轉(zhuǎn)移的少見(jiàn)病例,而這些特殊部位的遠(yuǎn)處轉(zhuǎn)移灶往往是傳統(tǒng)影像學(xué)檢查容易忽略的。
EC缺乏特異性的腫瘤標(biāo)記物,使臨床評(píng)估療效、監(jiān)測(cè)復(fù)發(fā)和轉(zhuǎn)移有一定的困難,PET/CT在病灶大小變化的基礎(chǔ)上結(jié)合SUV的變化反映療效。Nishiyama等[23]發(fā)現(xiàn)利用病灶18F-FDG攝取變化評(píng)價(jià)治療反應(yīng)的敏感度和特異度高達(dá)90%和80%。Sharma等[24]隨訪了101例懷疑復(fù)發(fā)的EC患者(51例復(fù)發(fā)),PET/CT診斷復(fù)發(fā)的敏感度、特異度及準(zhǔn)確度分別達(dá)88.9%、93.6%和91%,其中76例患者在1個(gè)月內(nèi)同時(shí)給予傳統(tǒng)影像學(xué)檢查(CI)評(píng)價(jià)復(fù)發(fā)與否,發(fā)現(xiàn)PET/CT相對(duì)CT(包括增強(qiáng)CT)和(或)MRI對(duì)治療后可疑復(fù)發(fā)的患者在診斷復(fù)發(fā)時(shí)有更高的特異度(96.4% vs. 62%)、準(zhǔn)確度(92.1% vs. 76.3%)、陽(yáng)性預(yù)測(cè)值(97.7% vs. 78.4%) 和陰性預(yù)測(cè)值(84.3% vs. 72%),但是兩者的敏感度相當(dāng)(89.5% vs. 85.1%)。Kadkhodayan等[25]報(bào)道PET/CT診斷EC治療后復(fù)發(fā)的敏感度高達(dá)95.8%,特異度為92.5%,并改變了22%~35%患者的治療方式。Ozcan Kara等[26]的研究也證實(shí)了這點(diǎn),該研究中PET/CT診斷EC治療后復(fù)發(fā)的敏感度更高達(dá)100%,敏感度及準(zhǔn)確度明顯優(yōu)于傳統(tǒng)影像及腫瘤標(biāo)記物糖鏈抗原125。鑒于低劑量CT較差的組織分辨率,很多臨床工作者建議采用PET結(jié)合增強(qiáng)CT評(píng)估EC復(fù)發(fā),但是Kitajima等[27]對(duì)比了PET增強(qiáng)CT與低劑量CT,發(fā)現(xiàn)兩者在評(píng)價(jià)復(fù)發(fā)方面無(wú)明顯差異。
PET/CT不僅可提供影像資料,還可進(jìn)行定量分析,其中常用定量指標(biāo)為SUVmax,與腫瘤的增殖、侵襲性以及葡萄糖轉(zhuǎn)運(yùn)體的表達(dá)有關(guān)。多項(xiàng)研究發(fā)現(xiàn),原發(fā)灶SUVmax越高,病灶侵襲性越強(qiáng)、預(yù)后越差、越易復(fù)發(fā)或轉(zhuǎn)移[7,28-32]。Nakamura等[30]隨訪了106例EC患者,發(fā)現(xiàn)原發(fā)灶SUVmax較高的患者無(wú)疾病進(jìn)展生存率及總體生存率均低于原發(fā)灶SUVmax相對(duì)低的患者,Ⅲ、Ⅳ期患者尤為明顯。多項(xiàng)研究證實(shí)原發(fā)灶SUVmax是總生存率的獨(dú)立預(yù)后因素,并且原發(fā)灶SUVmax在16.42~18.51為判斷預(yù)后的截?cái)嘀礫30-32]。但是,SUVmax僅代表腫瘤單一的代謝最活躍點(diǎn),不能評(píng)估整個(gè)腫瘤負(fù)荷,故而有學(xué)者提出了其他的定量指標(biāo),例如MTV和TLG。Liu等[33]收集了15例ⅣB期患者治療前的PET/CT,發(fā)現(xiàn)MTV和TLG可很好地預(yù)測(cè)總生存率,當(dāng)MTV大于450 ml時(shí)預(yù)后非常差,需要更積極的治療方式,但是該研究樣本量太少并且有選擇性偏倚。Shim等[34]分析了84例Ⅰ~Ⅳ期EC患者術(shù)前MTV與TLG,當(dāng)MTV ≥ 17.15 ml 、TLG ≥ 56.43時(shí),患者更易發(fā)生淋巴結(jié)轉(zhuǎn)移及術(shù)后復(fù)發(fā),是預(yù)測(cè)腫瘤復(fù)發(fā)的獨(dú)立因素。但是,目前有關(guān)MTV和TLG在EC中應(yīng)用的研究比較少,并且尚無(wú)勾畫(huà)MTV的統(tǒng)一標(biāo)準(zhǔn),使得這2個(gè)參數(shù)在臨床上應(yīng)用仍受到一定的限制。
PET/CT在EC盆腔、腹主動(dòng)脈旁淋巴結(jié)轉(zhuǎn)移、遠(yuǎn)處轉(zhuǎn)移及評(píng)價(jià)預(yù)后、復(fù)發(fā)診斷等方面具有其獨(dú)特的價(jià)值,不僅可以指導(dǎo)手術(shù)方式的選擇,避免不必要的過(guò)度手術(shù),而且原發(fā)灶SUVmax、MTV、TLG更有望作為一種術(shù)前評(píng)估預(yù)后的重要無(wú)創(chuàng)性參數(shù)。但是,PET/CT顯像在EC術(shù)前診斷存在不足,即便在子宮肌層浸潤(rùn)方面,其效能僅與MRI相似。但是,將PET/CT與MRI設(shè)備的結(jié)合應(yīng)用,不僅彌補(bǔ)了PET/CT在評(píng)估原發(fā)灶浸潤(rùn)范圍的不足,提高了單純MRI診斷淋巴結(jié)轉(zhuǎn)移的準(zhǔn)確度,而且最大化地降低了術(shù)后盆腔結(jié)構(gòu)紊亂對(duì)鑒別腫瘤復(fù)發(fā)的影響,增加了肝臟轉(zhuǎn)移瘤檢出的敏感度。也許將來(lái)PET/MRI有可能為EC的診斷開(kāi)創(chuàng)新的格局。
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(本文編輯:林燕薇)
Application of PET/CT in endometrial carcinoma
Liu Doudou, Liu Yifei, Zhang Tingjie, Cheng Muhua.
Department of Nuclear Medicine, the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China Corresponding author, Cheng Muhua,E-mail:chmarka@163.com
Endometrium carcinoma is one of the most common malignant tumors in gynecology, and the overall prognosis is good. Accurate preoperative staging and assessment of the risk of ectopic involvement determine the surgical approach and scope. PET/CT has a unique value in diagnosis of endometrium carcinoma, lymph node metastases of pelvic and para-aortic, distant metastasis, evaluating prognosis and recurrence diagnosis, etc. Furthermore, parameters such as maximum standard uptake value of primary lesion, total volume of cancer metabolism and total lesion glycolysis, etc, are expected to be the important non-invasive index to evaluate the prognosis of endometrial carcinoma.
Positron emission tomography; Endometrial carcinoma; Recurrence;Lymph node metastasis
10.3969/j.issn.0253-9802.2016.08.001
510630 廣州,中山大學(xué)附屬第三醫(yī)院核醫(yī)學(xué)科
,程木華,E-mail:chmarka@163.com
2016-05-05)