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      當(dāng)代前列腺動(dòng)脈栓塞術(shù)的文獻(xiàn)

      2019-06-09 08:40回顧譚宏宇祝清國(guó)
      醫(yī)學(xué)信息 2019年6期
      關(guān)鍵詞:良性前列腺增生

      回顧 譚宏宇 祝清國(guó)

      摘要:前列腺動(dòng)脈栓塞術(shù)作為一種嶄新的放射介入技術(shù),用于治療良性前列腺增生繼發(fā)下尿路癥狀的患者。良性前列腺增生癥是一種常見于中老年男性患者的臨床病癥,它常導(dǎo)致典型的下尿路癥狀,包括夜尿、尿頻、尿急、尿流率下降、排尿躊躇、不完全排空感等。通常在排除腫瘤、炎癥、中樞神經(jīng)系統(tǒng)疾病等病因后,由良性前列腺增生所引起的輕中度下尿路癥狀可行觀察療法或藥物治療,而對(duì)于中重度癥狀患者,則多建議手術(shù)治療。自早期偶然發(fā)現(xiàn)選擇性地前列腺動(dòng)脈栓塞術(shù)能治療因前列腺增生繼發(fā)的惡性出血,且可緩解下尿路癥狀之后,該方法被越來越多的臨床學(xué)者所接受,并積極探索該技術(shù)的實(shí)用性、安全性及有效性。目前,前列腺動(dòng)脈栓塞術(shù)仍未成為良性前列腺增生癥的標(biāo)準(zhǔn)療法。本文將重點(diǎn)回顧關(guān)于前列腺動(dòng)脈栓塞術(shù)的相關(guān)文獻(xiàn),包括個(gè)案、動(dòng)物研究、回顧性或前瞻性隊(duì)列研究等,對(duì)該技術(shù)進(jìn)行總結(jié)。

      關(guān)鍵詞:良性前列腺增生;前列腺動(dòng)脈栓塞術(shù);介入放射學(xué);下尿路癥狀

      中圖分類號(hào):R697.3? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?文獻(xiàn)標(biāo)識(shí)碼:A? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?DOI:10.3969/j.issn.1006-1959.2019.06.017

      文章編號(hào):1006-1959(2019)06-0048-04

      Abstract:As a new radiological interventional technique, prostate artery embolization is used to treat patients with benign prostatic hyperplasia secondary to lower urinary tract symptoms. Benign prostatic hyperplasia is a clinical condition common in middle-aged and elderly men. It often leads to typical lower urinary tract symptoms, including nocturia, frequent urination, urgency, decreased urinary flow rate, urinary fistula, incomplete emptying, etc. . Usually after the exclusion of tumors, inflammation, central nervous system diseases and other causes, mild to moderate urinary tract symptoms caused by benign prostatic hyperplasia are feasible observation therapy or drug treatment, and for patients with moderate to severe symptoms, surgery is recommended. Since the early accidental discovery of selective prostate artery embolization for the treatment of malignant hemorrhage secondary to benign prostatic hyperplasia, and can alleviate the symptoms of lower urinary tract, this method has been accepted by more and more clinical scholars, and actively explore the technology. Practicality, safety and effectiveness. At present, prostate arterial embolization has not become the standard treatment for benign prostatic hyperplasia. This article will focus on reviewing relevant literature on prostate artery embolization, including case studies, animal studies, retrospective or prospective cohort studies, and summarize the technique.

      Key words:Benign prostatic hyperplasia;Prostatic artery embolization;Interventional radiology; Lower urinary tract symptoms

      下尿路癥狀(lower urinary tract symptoms,LUTS)是一種常見臨床病征,在40歲以上的男性中常見[1],表現(xiàn)為尿頻、尿急、進(jìn)行性排尿困難、尿潴留等儲(chǔ)尿期癥狀及尿路變細(xì)及排尿中斷、滴瀝等排尿期癥狀及排尿后癥狀,與良性前列腺增生(benign prostate hyperplasia,BPH)引起的膀胱出口梗阻和刺激有關(guān)[2]。輕度LUTS治療主要以調(diào)整生活方式為主,而中重度LUTS可從藥物治療中獲益,如5α還原酶抑制劑、α受體阻滯劑、毒蕈堿受體拮抗劑、磷酸二酯酶抑制劑、植物制劑等[3]。對(duì)于繼發(fā)難治性下尿路癥狀的前列腺肥大患者,則主要采用前列腺手術(shù)治療為主。經(jīng)尿道前列腺電切術(shù)(transurithral resection of prostate,TURP)是金標(biāo)準(zhǔn),但其術(shù)后有一些潛在的并發(fā)癥,包括TURP綜合征(生理鹽水灌注導(dǎo)致的電解質(zhì)紊亂)、急性尿潴留、泌尿道感染、膀胱頸痙攣、尿道狹窄、逆行射精、勃起功能障礙、尿失禁及出血等[4]。而對(duì)于極其巨大的前列腺增生患者來說,開放性前列腺手術(shù)(open prostatectomy,OP)則是其一線治療方案,但術(shù)后住院時(shí)間會(huì)相對(duì)延長(zhǎng)[5],并出現(xiàn)泌尿道感染、尿失禁、尿道狹窄、膀胱頸痙攣等并發(fā)癥,更有可能出現(xiàn)大出血需要輸血治療,嚴(yán)重時(shí)會(huì)引起患者死亡[3]?;谝陨蠋c(diǎn),臨床亟待需要侵入性更小的手術(shù)治療方案,TURP的替代方案如像經(jīng)尿道微波熱療(TUMT)、經(jīng)尿道針刺消融術(shù)(TUNA)、經(jīng)尿道激光氣化術(shù)(PVP)、尿道前列腺懸提術(shù)(PUL)等。OP的替代方案有經(jīng)尿道激光前列腺剜除術(shù)(HoLRP)、腹腔鏡或機(jī)器人輔助地前列腺切除術(shù)等。近年來,前列腺動(dòng)脈栓塞術(shù)(prostatic artery embolization,PAE)異軍突起,作為一種新興的、安全且有效的手術(shù)替代方案治療繼發(fā)LUTS的BPH患者[6]。與其他手術(shù)方案對(duì)比,其優(yōu)勢(shì)在于:侵入性降到最小、無需住院、術(shù)后康復(fù)時(shí)間短、出現(xiàn)嚴(yán)重并發(fā)癥的風(fēng)險(xiǎn)低。然而,盡管有著可靠的數(shù)據(jù)支持著這項(xiàng)有前景的技術(shù),但PAE尚未成為BPH繼發(fā)LUTS患者的標(biāo)準(zhǔn)治療方案之一,依然需要更進(jìn)一步的研究予以支持。本文旨在回顧該技術(shù)的淵源、發(fā)展歷程、療效,并對(duì)既往發(fā)表的個(gè)案報(bào)道、動(dòng)物實(shí)驗(yàn)、回顧性或前瞻性隊(duì)列研究等進(jìn)行總結(jié)。

      1發(fā)展歷程

      自Mitchell ME等[7]首次將介入栓塞子宮肌瘤的技術(shù)轉(zhuǎn)向治療前列腺出血之后,隨著介入技術(shù)、微導(dǎo)管技術(shù)的進(jìn)一步發(fā)展,更微小的血管也能夠進(jìn)行栓塞[8-10]。DeMeritt JS等[10]報(bào)道了DSA輔助下采用150~250 μm聚乙烯醇經(jīng)右側(cè)髂內(nèi)動(dòng)脈完成了對(duì)膀胱下動(dòng)脈的栓塞,成功緩解了患者難以控制的血尿癥狀,研究觀察到LUTS明顯緩解,同時(shí)未見不良反應(yīng)和性功能障礙等并發(fā)癥,提示PAE可用于治療BPH。

      2動(dòng)物實(shí)驗(yàn)

      PAE的動(dòng)物實(shí)驗(yàn)于上個(gè)世紀(jì)八十年代就有文獻(xiàn)報(bào)道。巴西Sun F等[11,12]為了證明PAE的可行性及安全性,對(duì)豬、犬的動(dòng)物模型進(jìn)行栓塞研究,術(shù)后療效均可,并對(duì)組織病理上的特點(diǎn)及改變機(jī)制進(jìn)行進(jìn)一步的闡述。而Brook OR等[13]另辟蹊徑,在動(dòng)態(tài)對(duì)比增強(qiáng)磁共振成像(DCE-MRI)下對(duì)三種不同規(guī)格的栓塞劑進(jìn)行分析,栓塞前后繪制比格犬前列腺實(shí)質(zhì)及尿道周圍組織的灌注曲線圖予以求證。邱志磊等[14]的激素誘導(dǎo)動(dòng)物模型實(shí)驗(yàn)結(jié)果也對(duì)PAE給予了支持。

      3前列腺動(dòng)脈的解剖結(jié)構(gòu)

      前列腺動(dòng)脈(PA)直徑十分細(xì)小,在解剖學(xué)上極其復(fù)雜且變化多端。因此,要辨別其開口,或是將其從并行的血管分枝中區(qū)分出來,又或是從細(xì)小的動(dòng)脈吻合支將其識(shí)別,對(duì)術(shù)者來說是一種挑戰(zhàn)。想要成功地進(jìn)行PAE,避免非靶向的栓塞,全面了解其脈管結(jié)構(gòu)及與周圍組織的關(guān)系至關(guān)重要。

      早期Clegg EJ[15]對(duì)尸體盆腔脈管的研究介紹了前列腺由來源多變異的膀胱-前列腺動(dòng)脈供血,對(duì)腺體內(nèi)穿支動(dòng)脈的特殊螺旋樣結(jié)構(gòu)進(jìn)行了大致描述。此后Bouissou H等[16]提出了“頭側(cè)PA”及“尾側(cè)PA”的概念,并對(duì)其走行及供血特點(diǎn)加以說明;Garcia-Monaco R等[17]則將其描述為上下兩蒂,但走行及供血范圍大體一致。國(guó)內(nèi)Wang MQ[18]在DSA及錐體束CT輔助下對(duì)PA數(shù)量、來源及吻合支等數(shù)據(jù)進(jìn)行較為詳細(xì)地統(tǒng)計(jì)與分析。

      4 PAE的臨床療效

      4.1前瞻性研究? Antunes AA等[19]等報(bào)道了11例因BPH繼發(fā)急性尿潴留行PAE的研究,結(jié)果顯示PAE成功率為91%,平均隨訪日期為22.3個(gè)月,術(shù)后12個(gè)月隨訪,IPSS平均改善2.8分,QoL平均下降0.4分,Qmax提升6.6 ml/s,逼尿肌壓力下降了34.2 cm H2O,PSA則從12.1 ng/ml降至4.3 ng/ml,患者的總體臨床數(shù)據(jù)及尿流動(dòng)力學(xué)參數(shù)在術(shù)后都有所提高。Gao YA等[20]則通過隨機(jī)對(duì)照試驗(yàn)對(duì)TURP及PAE進(jìn)行研究,文獻(xiàn)共報(bào)道114例患者,隨機(jī)分成PAE組及TURP組,PAE手術(shù)成功率小于TURP(94.7%<100.0%),各組術(shù)后臨床指標(biāo)(IPSS、QoL、Qmax、PVR、PSA及PV)較入院時(shí)均顯著提高;對(duì)于TURP組來說,IPSS、QoL、Qmax、PVR在術(shù)后1~3個(gè)月時(shí)改善優(yōu)于PAE組;對(duì)于PSA及PV的改善情況,該組則在全程隨訪過程都表現(xiàn)出明顯優(yōu)勢(shì);但術(shù)后2年,兩組間的這些臨床指標(biāo)相差甚小。而在不良事件及并發(fā)癥的發(fā)生率方面,PAE表現(xiàn)較差(52.6% vs 29.8%)。英國(guó)學(xué)者Somani BK等[21]也于同年發(fā)表了相關(guān)研究,對(duì)具有顯著臨床癥狀的BPH患者行PAE治療的初步結(jié)果顯示患者IPSS均值24分,PV均值94.9 ml,6個(gè)月時(shí)IPSS及QoL分別為12分、2分,PV及Qmax改善了42%及32%,隨訪過程中未見PAE相關(guān)的嚴(yán)重并發(fā)癥。Wang MQ等[22]對(duì)高齡群體(>75歲)進(jìn)行研究,術(shù)前數(shù)據(jù)顯示高齡組基礎(chǔ)疾病多,Qmax、PV、PRV、PSA、IIEF-5表現(xiàn)較年輕組差,總體手術(shù)成功率為147/157(93.6%),手術(shù)時(shí)間及成功率同樣表現(xiàn)較差(115.0±25.0 vs 95.0±15.0,P=0.037;90.5% vs 96.8%,P=0.061),考慮為老年人更可能出現(xiàn)血管斑塊因素所致;術(shù)后隨訪,除IIEF-5外,余數(shù)據(jù)均與術(shù)前表現(xiàn)有顯著統(tǒng)計(jì)學(xué)差異;但老年組PV減少更多(41.9%,P=0.031)。Carnevale FC等[23]對(duì)TURP與初始PAE組及“先近端栓塞,后遠(yuǎn)端栓塞(PErFecTED)”的PAE組臨床及尿流動(dòng)力結(jié)果進(jìn)行了隨機(jī)對(duì)照實(shí)驗(yàn),顯示這三個(gè)組的IPSS、QoL、Qmax、PV均顯著改善;尤其是在IPSS評(píng)分,TURP組及“PErFecTED”組顯著低于初始PAE組,且這兩組間無顯著差異;而對(duì)于PV、Qmax來說,TURP則較其他兩組更具有優(yōu)勢(shì),但TURP并發(fā)癥發(fā)生率更高,包括尿失禁(26.7%),前列腺包膜破裂(6.7%),逆行射精(100%)等。

      4.2回顧性研究? Bagla S等[24]于2015年將其早期PAE試驗(yàn)例數(shù)擴(kuò)充至78例,評(píng)估3組不同PV(1組:PV<50 ml,2組:PV在50~80 ml,3組:PV>80 ml)之間的AUA評(píng)分、QoL及IIEF。78例患者中75例雙側(cè)栓塞成功,其中僅出現(xiàn)了2例輕微并發(fā)癥,為腹股溝血腫及泌尿道感染;該團(tuán)隊(duì)還表示3組患者AUA癥狀評(píng)分及QoL均減少,但組間AUA癥狀評(píng)分、QoL及IIEF無明顯統(tǒng)計(jì)學(xué)差異。Pisco JM[25]團(tuán)隊(duì)對(duì)630例患者進(jìn)行近五年的中長(zhǎng)期隨訪結(jié)果顯示:門診即可行PAE,術(shù)后可立即出院578例,218例(34.6%)在術(shù)后出院時(shí)即表達(dá)LUTS明顯緩解;手術(shù)成功618例(98.10%),其中雙側(cè)栓塞572例(92.6%),單側(cè)栓塞46例(7.4%);術(shù)中85.2%的患者均未感受到疼痛。47例失訪,104例臨床癥狀未改善或加重,85例短期(1年內(nèi)),14例中期(1~3年),5例長(zhǎng)期(3~6.5年);患者IPSS、Qmax、QoL、PV、PSA、PVR與術(shù)前相比差異具有統(tǒng)計(jì)學(xué)意義;并發(fā)癥包括1例局部膀胱壁缺血壞死及1例間斷反復(fù)發(fā)作的恥骨后疼痛,余下如血尿、血精、尿頻等并發(fā)癥均為輕度,自行緩解;總體臨床成功率分別為85.1%(短期12個(gè)月內(nèi))、81.9%(中期)、76.3%(長(zhǎng)期6.5年),提示PAE可作為一線治療方法的迭代方案。Isaacson AJ等[26]首次通過球囊裝置成功施行PAE。他們利用了該裝置抗反流的特點(diǎn)對(duì)平均年齡為65歲的12例患者進(jìn)行了栓塞(栓塞劑未統(tǒng)一標(biāo)準(zhǔn)),平均隨訪(22±8)個(gè)月,IPSS、QoL明顯改善(P<0.01),除尿頻、排尿困難等一過性栓塞并發(fā)癥,余未見輕微或嚴(yán)重的發(fā)癥。

      4.3個(gè)案? Kisilevzky N等[27]對(duì)1例PV約300 cm3的58歲男性患者施行PAE手術(shù),因術(shù)中發(fā)現(xiàn)PA借助主干APA反流栓塞劑至陰莖動(dòng)脈及海綿體動(dòng)脈,進(jìn)而出現(xiàn)了龜頭尿道外口處部分缺血壞死灶;術(shù)后積極擴(kuò)血管、抗炎及局部皮膚護(hù)理,術(shù)后14 d龜頭壞死區(qū)域部分皮下可見新生肉芽組織,拔除尿管后患者已能自行排尿;第40天時(shí)壞死區(qū)全部愈合,患者排尿順暢,開始規(guī)律的性生活。術(shù)后60 d隨訪,PV縮小至150 g,幾乎未見PVR,PSA也從24 ng/dl降為5.42 ng/dl。Kably I等[28]曾積極治療過一位低風(fēng)險(xiǎn)前列腺癌伴肉眼血尿及尿潴留的患者,既往行膀胱鏡下碎石治療,后病情復(fù)發(fā),膀胱鏡檢查提示顯著增大的前列腺兩側(cè)葉及中葉和數(shù)顆直徑約2~3 cm的結(jié)石,擬行PAE以縮小前列腺葉體積后再行手術(shù)取出結(jié)石;手術(shù)成功進(jìn)行,術(shù)后48 h后患者意外在家自行排出7顆結(jié)石,且無明顯痛感及血尿癥狀。術(shù)后隨訪3個(gè)月,IPSS從21分下降為2分,QoL為1分,男性性健康量表得分也從21分(輕度性功能障礙)提升至24分(正常性功能),PSA則從10.87 ng/ml下降為0.4 ng/ml,影像學(xué)檢查也提示PV減少了約70%。分析可能的原因是短期內(nèi)前列腺質(zhì)地的改變(凝固性壞死)促進(jìn)了結(jié)石順利進(jìn)入尿道排空。

      4.4其他? Shim SR等[29]通過薈萃分析和Meta回歸系統(tǒng)評(píng)價(jià)了往年多篇PAE相關(guān)文獻(xiàn),認(rèn)可了PAE的安全性及有效性,但納入的文獻(xiàn)并未客觀地評(píng)判PAE的療效,且未對(duì)PAE的缺點(diǎn)(如AUR、輻射暴露等)給予足夠地重視,目前PAE仍然不及標(biāo)準(zhǔn)治療方法。Maclean D等[30]針對(duì)PAE術(shù)后療效的預(yù)測(cè)提供了不同的看法。其成功栓塞數(shù)十名患者,記錄隨訪期間包括IPSS、QoL、PV等數(shù)據(jù),經(jīng)由Pearson雙變量分析及多元線性回歸分析以評(píng)估臨床改善與其他變量之間的關(guān)聯(lián)強(qiáng)度,最后發(fā)現(xiàn)“前列腺初始體積”及“術(shù)后3個(gè)月時(shí)的體積減少的百分比”能很好地預(yù)示12個(gè)月時(shí)的臨床療效。

      5總結(jié)與展望

      依現(xiàn)有數(shù)據(jù)來說,PAE似乎是治療由BPH引起的LUTS的有效且安全的一種微創(chuàng)技術(shù),其方便、快捷,于門診即可快速開展。然而,即便是經(jīng)驗(yàn)十足的介入放射科醫(yī)師,PAE也依然具有挑戰(zhàn)性,因此掌握盆腔血管尤其是PA的解剖特點(diǎn)和準(zhǔn)確的術(shù)前及術(shù)中影像學(xué)檢查顯得尤為重要。

      盡管有多項(xiàng)研究證明PAE在改善LUTS方面是安全且有效的,但RCT數(shù)據(jù)量仍不夠龐大。此外,也需更充足更有說服力的數(shù)據(jù)來支持PAE在改善泌尿道癥狀方面的優(yōu)勢(shì)。而未來的實(shí)驗(yàn)設(shè)計(jì)應(yīng)圍繞著以下要素展開:多中心、前瞻性的RCTs--PAE與OP、TURP以及其他經(jīng)尿道的手術(shù)等治療方法做對(duì)比、長(zhǎng)期隨訪工作等。當(dāng)有了更全面的RCT、更龐大的患者群以及更長(zhǎng)久的隨訪工作,那么PAE在BPH治療方案中的地位將更難以撼動(dòng)。另外,還有以下若干問題亟待解決:栓塞材料的最佳類型和規(guī)格、復(fù)雜解剖條件下導(dǎo)管種類的抉擇收益、預(yù)防栓塞劑反流及非靶器官栓塞的手術(shù)技巧、不同動(dòng)脈穿刺途徑的潛在益處及輔助影像檢查的搭配策略等。

      參考文獻(xiàn):

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      收稿日期:2018-12-6;修回日期:2019-1-17

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