譚書(shū)韜,吳 斌

TURP術(shù)前非那雄胺應(yīng)用時(shí)間對(duì)圍術(shù)期出血的影響

譚書(shū)韜,吳 斌*

目的 評(píng)價(jià)術(shù)前非那雄胺應(yīng)用時(shí)間對(duì)經(jīng)尿道前列腺切除術(shù)(Transurethral resection of prostate,TURP)術(shù)中及術(shù)后出血量的影響。方法 226例良性前列腺增生癥(Benign prostatic hyperplasia,BPH)患者,術(shù)前服用1周非那雄胺5 mg的80例患者納為1周組,服用2周的78例患者納為2周組,未服用非那雄胺的68例患者納為對(duì)照組,比較三組的手術(shù)時(shí)間、術(shù)中出血量、術(shù)中及術(shù)后沖洗液量、術(shù)后沖洗時(shí)間、出血指數(shù)及強(qiáng)度等。結(jié)果 226例TURP術(shù)均獲得成功。與對(duì)照組比較,1周組和2周組的手術(shù)時(shí)間縮短、術(shù)中失血量、術(shù)中及術(shù)后沖洗液量減少，出血指數(shù)均顯著降低,2周組術(shù)后沖洗時(shí)間、出血強(qiáng)度顯著降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。與1周組比較,2周組手術(shù)時(shí)間縮短，術(shù)中失血量、術(shù)中沖洗液量減少，出血指數(shù)顯著降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論 TURP術(shù)前2周服用非那雄胺可有效縮短TURP手術(shù)時(shí)間,減少術(shù)中及術(shù)后失血量。

良性前列腺增生;TURP;出血;非那雄胺

0 引言

經(jīng)尿道前列腺切除術(shù)(Transurethral resection of prostate,TURP)是藥物控制不佳的中重度良性前列腺增生(Benign prostatic hyperplasia,BPH)的標(biāo)準(zhǔn)治療,是手術(shù)治療的金標(biāo)準(zhǔn)[1]。術(shù)中及術(shù)后出血是TURP最常見(jiàn)的并發(fā)癥之一,可能導(dǎo)致術(shù)中視野差、患者血流動(dòng)力學(xué)不穩(wěn)定、血凝塊填塞膀胱,甚至需要二次手術(shù)治療[2]。過(guò)去幾十年,為了減少TURP術(shù)中及術(shù)后出血,研究者嘗試應(yīng)用過(guò)各種形式的促凝劑或硬化劑(如纖維蛋白粘合劑等),但這些方法的應(yīng)用有一定的困難或局限性,有的甚至導(dǎo)致前列腺窩瘢痕的形成,導(dǎo)致術(shù)后排尿困難。由于5α-還原酶抑制劑非那雄胺對(duì)前列腺內(nèi)血管生長(zhǎng)因子的調(diào)節(jié)作用,有研究者已經(jīng)開(kāi)始注意其對(duì)于減少TURP圍術(shù)期出血的治療效果。目前已證明，應(yīng)用非那雄胺可減少前列腺內(nèi)血管內(nèi)皮生長(zhǎng)因子(VEGF,一種有效的血管生成生長(zhǎng)因子)的表達(dá)以及微血管密度(MVD)的水平[3]。但對(duì)術(shù)前服用藥物的時(shí)間尚缺乏深入研究。本文探討了術(shù)前服用非那雄胺不同時(shí)間對(duì)TURP圍術(shù)期出血的影響,現(xiàn)報(bào)道如下。

1 資料與方法

1.1 臨床資料 選取2011年6月至2016年6月我院泌尿外科收治的行TURP患者226例,隨機(jī)分為對(duì)照組68例。服用非那雄胺1周組(1周組)80例和服用非那雄胺2周組(2周組)78例,統(tǒng)計(jì)三組患者年齡、前列腺體積、國(guó)際前列腺癥狀評(píng)分(IPSS)，殘余尿量、最大尿流率、前列腺切除重量等一般資料。

1.2 納入及排除標(biāo)準(zhǔn) 納入標(biāo)準(zhǔn):患者年齡60～80歲,前列腺體積40～80 mL,有BPH手術(shù)指征,患者有手術(shù)要求,除外手術(shù)禁忌及藥物禁忌,服用阿司匹林者停用2周以上。

排除標(biāo)準(zhǔn):前列腺體積>80 mL或<40 mL;伴神經(jīng)源性膀胱;伴凝血功能異常;術(shù)前服用治療BPH的植物藥或性激素制劑;術(shù)后病理報(bào)告并發(fā)有前列腺癌者。

1.3 方法 1周組術(shù)前口服非那雄胺1周,1次/d,每次5 mg;2周組術(shù)前口服非那雄胺2周,1次/d,每次5 mg;對(duì)照組術(shù)前不應(yīng)用非那雄胺。術(shù)前患者完善國(guó)際前列腺癥狀評(píng)分(IPSS),前列腺特異性抗原(PSA),前列腺超聲,最大尿流率,尿流動(dòng)力學(xué)檢查。前列腺體積計(jì)算公式為π/6×長(zhǎng)度(cm)×寬度(cm)×高度(cm)。采用腰-硬聯(lián)合麻醉,手術(shù)均由同一組泌尿外科醫(yī)生完成,沖洗液應(yīng)用4%甘露醇,手術(shù)切除范圍均達(dá)到前列腺外科包膜。

1.4 觀察指標(biāo) 記錄每例手術(shù)時(shí)間,術(shù)中、術(shù)后沖洗液量及術(shù)后沖洗時(shí)間。術(shù)中出血量測(cè)定:沖洗液桶內(nèi)加入肝素液,手術(shù)后充分?jǐn)噭驔_洗液,取5 mL標(biāo)本檢測(cè)血紅蛋白濃度,檢測(cè)方法為氰化高鐵血紅蛋白比色法。出血量(mL)=沖洗液中血紅蛋白濃度(g/L)×沖洗液量(L)/患者術(shù)前的血紅蛋白濃度(g/L)×1 000[4]。根據(jù)每例患者的前列腺切除組織重量和手術(shù)時(shí)間,計(jì)算出血指數(shù)(平均切除每克前列腺組織的失血量)及出血強(qiáng)度(平均每分鐘的出血量)。

2 結(jié)果

2.1 一般資料比較 三組患者的年齡、前列腺體積、IPSS評(píng)分、術(shù)前最大尿流率、手術(shù)切除前列腺重量比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表1。

表1 三組一般資料比較

2.2 觀察指標(biāo)比較 與對(duì)照組比較,1周組手術(shù)時(shí)間、術(shù)中失血量、術(shù)中沖洗液量、術(shù)后沖洗時(shí)間、出血指數(shù)均明顯降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。與對(duì)照組比較,2周組術(shù)后沖洗液量、出血強(qiáng)度顯著降低(P<0.05)。2周組與1周組比較,手術(shù)時(shí)間、術(shù)中沖洗液量、術(shù)中失血量、出血指數(shù)差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。見(jiàn)表2。

表2 三組臨床指標(biāo)比較

注：*與對(duì)照組比較，P<0.05；#與1周組比較，P<0.05

3 討論

BPH是引起老年男性下尿路癥狀(LUTS)最主要的原因之一,60歲以上的老年男性中約有超過(guò)一半受其影響,BPH患者不但前列腺腺體增生,其血管生成也明顯增加[5]。TURP是中重度BPH患者手術(shù)治療的常用術(shù)式,其中最重要的并發(fā)癥之一是術(shù)中及術(shù)后出血[6]。探索術(shù)前適當(dāng)用藥,從而有效控制TURP術(shù)中及術(shù)后出血,特別是對(duì)于那些手術(shù)風(fēng)險(xiǎn)較高的BPH患者,將提高TURP的安全性。非那雄胺是一種Ⅱ型5α-還原酶抑制劑,可以阻止睪酮變?yōu)榛钚愿叩碾p氫睪酮(DHT)。有研究已經(jīng)證明，前列腺內(nèi)血管受DHT影響,其可以誘導(dǎo)前列腺上皮和基質(zhì)細(xì)胞血管活性介質(zhì)的表達(dá),如VEGF[7]。有研究表明,BPH合并血尿患者的MVD顯著高于未合并血尿的患者,說(shuō)明MVD可以作為前列腺微血管增殖的指示之一,同時(shí)，其可能在TURP圍術(shù)期出血中起重要作用[8]。VEGF表達(dá)增加及MVD被認(rèn)為是導(dǎo)致BPH相關(guān)頑固性血尿的主要機(jī)制,亦是TURP術(shù)中及術(shù)后出血的主要原因之一[9]。作為5α-還原酶抑制劑,非那雄胺可降低前列腺內(nèi)DHT的水平。Lekas等[10]研究表明，非那雄胺可以降低前列腺內(nèi)MVD及VEGF水平。Donohue等[3]研究表明，應(yīng)用非那雄胺2周后,前列腺標(biāo)本的MVD顯著降低。Jia等[11]在動(dòng)物模型中使用增強(qiáng)磁共振成像評(píng)估前列腺的微循環(huán),發(fā)現(xiàn)服用非那雄胺后前列腺血流灌注明顯減少。 為了降低TURP術(shù)中及術(shù)后出血,可以術(shù)前應(yīng)用5α-還原酶抑制劑減少前列腺微循環(huán),減少BPH患者的MVD及TURP術(shù)中、術(shù)后出血[12]。Hagerty等[13]首先提出術(shù)前應(yīng)用非那雄胺治療對(duì)患者有益,能夠顯著減少輸血、血塊填塞膀胱和持續(xù)性肉眼血尿等情況。?zdal等[14]研究表明，TURP術(shù)前應(yīng)用非那雄胺可以減少術(shù)中及術(shù)后出血,療效肯定。Crea等[15]研究表明，術(shù)前應(yīng)用非那雄胺可以減少術(shù)后血紅蛋白的降低水平。Pastore等[16]研究表明,TURP術(shù)前應(yīng)用5α-還原酶抑制劑度他雄胺，有利于抑制術(shù)后血紅蛋白的下降。另有一項(xiàng)研究表明,TUPR術(shù)前應(yīng)用度他雄胺，可以有效減少大前列腺(>50 mL)的術(shù)中失血[17]。本研究結(jié)果顯示,與對(duì)照組比較，1周組的手術(shù)時(shí)間縮短，術(shù)中失血量減少，術(shù)中沖洗液量減少，術(shù)后沖洗時(shí)間縮短，出血指數(shù)降低，2周組的術(shù)后沖洗液量、出血強(qiáng)度也優(yōu)于對(duì)照組。提示術(shù)前服用非那雄胺可減少TURP術(shù)中及術(shù)后的出血。

關(guān)于TURP術(shù)前治療的最佳時(shí)間尚未達(dá)成共識(shí)。TURP術(shù)中及術(shù)后出血量與前列腺組織內(nèi)血管生成及腺體內(nèi)血管密度有關(guān),而5α-還原酶抑制劑作用一定時(shí)間后才可對(duì)前列腺血管生成及密度產(chǎn)生影響[18]。目前，國(guó)內(nèi)TURP術(shù)前應(yīng)用非那雄胺的時(shí)間有1周或2周[19-20],而對(duì)于最優(yōu)應(yīng)用時(shí)間缺乏相應(yīng)研究。國(guó)際上TURP術(shù)前應(yīng)用5α-還原酶抑制劑的時(shí)間較國(guó)內(nèi)延長(zhǎng)。Khwaja等[21]研究表明，術(shù)前服用非那雄胺2周，可顯著減少前列腺組織中的MVD。Donohue等[3]在TURP術(shù)前2周應(yīng)用非那雄胺的患者中也觀察到了這種血管生成抑制效果。而Aminsharifi等[22]認(rèn)為，服用非那雄胺2周，可減少TURP術(shù)中出血,對(duì)于大體積前列腺的手術(shù)，可以適當(dāng)延長(zhǎng)服用非那雄胺時(shí)間。Pastore等[23]研究表明,另一種5α-還原酶抑制劑度他雄胺使用6周，可減少BPH手術(shù)的出血量。新近研究認(rèn)為，對(duì)于一般TURP,術(shù)前應(yīng)用非那雄胺2周，可有效減少術(shù)中及術(shù)后出血[21-22]。本研究結(jié)果也表明，術(shù)前應(yīng)用非那雄胺2周,在手術(shù)時(shí)間、術(shù)中沖洗液量、術(shù)中失血量、出血指數(shù)方面均明顯優(yōu)于服用1周者,可以更好地降低圍術(shù)期的出血。

綜上所述,TURP術(shù)前應(yīng)用非那雄胺，能有效減少術(shù)中及術(shù)后出血,術(shù)前應(yīng)用2周非那雄胺更為適宜。未來(lái)仍需進(jìn)一步的研究來(lái)探索TURP術(shù)前應(yīng)用非那雄胺的最適宜時(shí)間。

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Effect of different courses of preoperative finasteride on perioperative bleeding in patients with

TURP TAN Shu-tao,WU Bin*

(Department of Urology,Shengjing Hospital of China Medical University,Shenyang 110004,China)

Objective To evaluate the effect of different courses of preoperative finasteride on the amount of perioperative bleeding during and after transurethral resection of prostate (TURP).Methods Totally 226 patients with benign prostatic hyperplasia (BPH) were scheduled for TURP,80 of them received 5 mg of finasteride daily for 1 week before surgery (group A),78 of them received finasteride for 2 weeks (group B),and the other 68 patients didn′t receive finasteride (control group).The operating time,intraoperative blood loss,intraoperative & postoperative irrigating fluid volume,postoperative irrigating time,bleeding index and intensity of the three groups were compared.Results The operation was successfully completed in 226 cases.Compared with control group,the operating time,intraoperative blood loss,intraoperative & postoperative irrigating fluid volume and bleeding index of group A and group B were significantly decreased,and the postoperative irrigating time and blood loss of group B were significantly decreased,the differences being significant (P<0.05).There were significant differences in the operating time,intraoperative blood loss,intraoperative irrigating fluid volume and bleeding index between group A and group B(P<0.05).Conclusion The use of finasteride two weeks before TURP can shorten the operating time and reduce perioperative and postoperative bleeding.

BPH;TURP;Bleeding;Finasteride

2016-09-18

中國(guó)醫(yī)科大學(xué)附屬盛京醫(yī)院泌尿外科,沈陽(yáng) 110004

*通信作者

10.14053/j.cnki.ppcr.201703012