胰腺導管內(nèi)乳頭狀黏液瘤診治進展

蔚藍色淼 2018-04-13

展開全文

胰腺導管內(nèi)乳頭狀黏液腫瘤（IPMN）是一種罕見的胰腺囊性腫瘤，上世紀70年代和80年代第一次報道了該病例[1]。20世紀90年，IPMN正式被命名，并成為胰腺囊性腫瘤一個特殊疾病[2]。IPMN占所有胰腺腫瘤的不足10%，及所有胰腺囊性腫瘤的25%左右[3]。大多數(shù)IPMN患者年位于60歲至70歲之間。男性患病率略高于女人[4]。近年來，隨著大量檢查儀器和外科器械的發(fā)明以及許多創(chuàng)新手術(shù)技術(shù)的不斷涌現(xiàn)， IPMN在診斷、治療以及預后等各個方面均取得了巨大進展。本文針對IPMN在診斷及外科治療及其預后等方面做一綜述。

1：定義及其分型
1.1 胰腺導管內(nèi)乳頭狀黏液腫瘤（IPMN）起源于胰腺導管上皮，呈乳頭狀增生，分泌過多的黏液，其特征是囊性或囊性擴張的分支胰管（Branch Ductal-IPMN，BD-IPMN和/或主胰管（Main Ductal-IPMN，MD-IPMN）。IPMN是一個可見的實體，不同于胰腺上皮內(nèi)腫瘤（PanIN），它被定義為一個微觀病變[5]。IPMN腫瘤大多位于胰腺頭（70%），約20%位于胰體及胰尾，約10% - 5%呈腺體彌漫性受累。大多數(shù)是單發(fā)病灶但20% - 40%為多發(fā)病灶[ 6.7]。
1.2 IPMN根據(jù)它們的結(jié)構(gòu)來源分為：胰腺主導管（16%至36%），胰腺支導管型（BD）（40%到65%）和混合或組合式（15%至23%）[ 8.9 10.11]，這種分類反映了重要的生物學差異及預后[ 12.13]。主胰管可輕度擴張，也可同時伴有胰腺萎縮。混合型表現(xiàn)為胰腺鉤突分支胰管擴張合并主胰管擴張，也可表現(xiàn)為體尾部分支胰管和主胰管擴張的組合。然而，并不是所有IPMN病例都被認為存在潛在的惡性[14.15]，如腫瘤內(nèi)出現(xiàn)>10 mm的實性結(jié)節(jié)、主胰管擴張>10mm、彌漫性或多中心起源、壁內(nèi)鈣化及糖尿病臨床癥狀，應高度警惕，提示為惡性IPMN。大多數(shù)MDIPMN和混合型IPMN，臨床表現(xiàn)出惡性腫瘤的特征（即重度異型增生或癌），其中45%與浸潤性癌相關(guān)[ 16.17.18]。相反，大多數(shù)BD型顯示低度發(fā)育不良，只有約15%是與浸潤性癌。
2 診斷及鑒別診斷：
2.1鑒別診斷：根據(jù)患者年齡，臨床表現(xiàn)和放射學結(jié)果。[ 16.19.20.21.22.23.24.25.26]，胰腺的幾個病變可以與IPMN相鑒別，其中最可能被誤診為IPMN的胰腺疾病包括慢性胰腺炎、粘液性囊腺瘤，單純性囊腫，漿液性囊腺瘤，和假性囊腫[27.28] 。
2.2診斷:胰腺囊性腫瘤的術(shù)前診斷準確性仍需優(yōu)化。目前臨床挑戰(zhàn)是建立一個可根據(jù)臨床隨訪和影像學確定是否需要手術(shù)。多層螺旋CT3D重建作為一種非侵入性的，方便和廣泛應用的成像方法，可以提供詳細的資料，對胰腺囊性病變[29]?！拜^大”的大小對非侵入性的成像可以做出診斷，而EUS-FNA可以幫助識別“小”囊腫，高級別/浸潤性腫瘤[30]。超聲內(nèi)鏡（EUS）和細針穿刺（FNA）聯(lián)合，該項技術(shù)被廣泛用于診斷實施,。據(jù)報道增強超聲內(nèi)鏡（CE-EUS）可將BD-IPMN合并壁結(jié)節(jié)的診斷率提高到98%[31]，Iannicelli等人提到胰泌素刺激與MRCP能夠更好地顯示腫瘤和導管系統(tǒng)之間的關(guān)系，從而確定診斷[32 ]。Chen等人發(fā)現(xiàn),超聲造影將BD-IPMN與漿液性囊腺瘤分辨出來是有幫助的[33]。
3. 治療：
因MD-IPMN有較大的惡變可能性，國際胰腺學會（IAP）推薦手術(shù)切除MD-IPMN，但是對于BD-IPMN的治療取決于腫瘤是否有浸潤傾向[34]；同樣仙臺共識指南也制定了對于IPMN的治療手段；他們于2006年出臺了相關(guān)指南并于2012年進行了修正，2012仙臺標準建議對于MD-IPMN患者推薦手術(shù)切除，而對于分支胰管內(nèi)乳頭狀黏液性腫瘤（BD-IPMN）內(nèi)徑達3厘米或更大的沒有任何額外的“高風險”的因素存在，可密切觀察。對于BD-IPMN的治療療更加傾向于保守，治療手段取決于腫瘤的大小、胰管直徑、存在胰腺炎與否等方面[16]，但這些指導方針基于專家意見，而不是存在強大的臨床數(shù)據(jù)，仍需大量臨床數(shù)據(jù)的支持。對于IPMN浸潤型行配套輔助放化療，可根據(jù)患者的術(shù)中及術(shù)后病理結(jié)果，包括所有陽性淋巴結(jié)和淋巴結(jié)陰性的患者，制定方案，霍普金斯大學一個團隊的研究表明，輔助化療將減少57%的死亡率，對于淋巴結(jié)轉(zhuǎn)移陽性的患者，輔助化療效果更加明顯[35]。
5. 總結(jié)：
雖然IPMN占胰腺腫瘤的比例不足10%。然而，值得關(guān)注的是，如果未經(jīng)恰當?shù)奶幚淼?，他們中的一些可能會跟隨不典型增生的癌序列，從而進展為浸潤性癌。因為IPMN的發(fā)病率較低，我們對IPMN這種疾病的認識仍是不完整的。盡管放射學科及各種檢查技術(shù)的進步，它仍然有時很難從其他良性病變區(qū)分。但就目前來說,對于MD-IPMN患者，適合手術(shù)切除。對于具有侵襲性IPMN治療，是將胰體尾切除術(shù)并周圍淋巴結(jié)清掃，同時限制切除無創(chuàng)性病變。對于IPMN的診療指南，仍需臨床大數(shù)據(jù)的支持。
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