低位直腸癌的治療

李政昌

·述評(píng)·

低位直腸癌的治療

李政昌

從1998年開(kāi)始，針對(duì)低位直腸癌，成功大學(xué)附屬醫(yī)院結(jié)直腸癌治療團(tuán)隊(duì)一直使用術(shù)前放射及化學(xué)治療，之后再行手術(shù)治療，同時(shí)建造保護(hù)性腸造口。術(shù)后加以輔助化療，化療療程結(jié)束后，再將腸道造口關(guān)閉。十年來(lái)，大多數(shù)患者都能順利完成治療且都存活至今，在此介紹我們的治療經(jīng)驗(yàn)。

直腸腫瘤； 直腸結(jié)腸切除術(shù)，重建性； 放射治療劑量； 藥物療法，聯(lián)合

傳統(tǒng)上針對(duì)低位直腸癌，唯一的手術(shù)根治方法就是腹會(huì)陰全切除手術(shù)(abdominoperineal resection,APR)。自從Heald[1]教授于1982年發(fā)表了直腸及全系膜切除手術(shù)(total mesorectal excision，TME)后，低位直腸癌的治療方法有了長(zhǎng)足的進(jìn)步。這個(gè)手術(shù)最大的效果就是有效降低了癌癥局部復(fù)發(fā)率。同時(shí)，隨著醫(yī)師外科解剖知識(shí)的進(jìn)步、新化療藥物的誕生，直腸癌的整體存活率也有顯著提高。對(duì)于局部侵犯較厲害的低位直腸癌而言，很多臨床報(bào)告都指出，術(shù)前放射及化學(xué)治療能夠有效縮小腫瘤的體積，提高了腫瘤完整切除的比率，且患者肛門括約肌保留的比率也大為提高[2-3]。為求更好的腫瘤控制率，腫瘤科醫(yī)師開(kāi)始加入了更新、更強(qiáng)的化療藥。但是，更新、更強(qiáng)的化療藥有時(shí)候會(huì)對(duì)患者造成較大的毒性，甚至無(wú)法再接受后續(xù)的治療。有鑒于此，我們的治療團(tuán)隊(duì)從1998年開(kāi)始，在術(shù)前采用較低劑量的5-氟尿嘧啶配合放射治療，目標(biāo)是讓患者接受完整療程后，仍有體力接受手術(shù)治療，以提高治愈的機(jī)會(huì)，且為了減少低位直腸癌患者術(shù)后吻合口漏的發(fā)生，我們采用暫時(shí)性橫結(jié)腸或回腸造瘺的方法，大幅度提升了保存肛門括約肌的機(jī)率。

一、手術(shù)治療低位直腸癌的相關(guān)因素

對(duì)于中低位直腸癌，外科醫(yī)師會(huì)在患者俯臥的姿勢(shì)下，用硬式直腸鏡或肛診來(lái)初步判定腫瘤距離肛門口的距離及腫瘤侵犯腸壁深度，再用計(jì)算機(jī)斷層掃描檢查局部淋巴結(jié)及遠(yuǎn)處擴(kuò)散的程度，以決定是否需要接受術(shù)前放化療。若上述檢查仍無(wú)法確診，需行核磁共振或直腸超聲內(nèi)鏡檢查以幫助臨床診斷。在接受完整放化療后，需再做相同檢查，以評(píng)估治療的成效。術(shù)后的肛門功能及排便次數(shù)會(huì)以紀(jì)念斯隆-凱特林癌癥中心的肛門功能評(píng)分(memorial sloan-kettering cancer center anal function scores，MSK-AF)[4]做為判定。

對(duì)于已接受術(shù)前放化療的直腸癌患者，“遠(yuǎn)端切除邊緣”(distal resection margin)是一個(gè)影響腫瘤局部復(fù)發(fā)的重要因素。我們的治療經(jīng)驗(yàn)顯示，接受術(shù)前放化療和全系膜切除手術(shù)的低位直腸癌患者都能達(dá)到至少2 cm的遠(yuǎn)端切除邊緣[5]。有研究顯示，這類患者只需達(dá)到1 cm的遠(yuǎn)端切除邊緣就已足夠[6]。此外，環(huán)周切緣(circumferential resection margin)是另一個(gè)重要的預(yù)后因素[7]。對(duì)直腸癌患者而言，腫瘤如果侵犯到手術(shù)的環(huán)周切緣，患者的5年存活率、癌癥的局部復(fù)發(fā)及遠(yuǎn)處轉(zhuǎn)移率都會(huì)受到很大的影響[8-9]。這種影響對(duì)于術(shù)前未接受放療的患者尤其明顯。對(duì)于術(shù)前已接受放療的患者，腫瘤侵犯至環(huán)周切緣的機(jī)會(huì)大大減少，雖然對(duì)癌癥局部復(fù)發(fā)及遠(yuǎn)處轉(zhuǎn)移的影響仍然存在，但相對(duì)于未接受放療的患者而言其影響較小。近年來(lái)的研究顯示，若術(shù)前的放化療能達(dá)到病理腫瘤細(xì)胞完全緩解(pathological complete response，PCR)，則患者術(shù)后的局部復(fù)發(fā)率會(huì)明顯降低[10-12]。

在低位直腸癌患者中，和未接受術(shù)前放化療的患者相比，接受過(guò)術(shù)前放化療的患者手術(shù)標(biāo)本中通常不會(huì)找到很多淋巴結(jié)，通常都會(huì)少于12個(gè)[13-14]。但是，如果在這樣的手術(shù)標(biāo)本中仍能夠發(fā)現(xiàn)淋巴結(jié)轉(zhuǎn)移，往往提示患者不良的預(yù)后[15]。經(jīng)我科室手術(shù)的患者，其術(shù)后標(biāo)本的淋巴結(jié)個(gè)數(shù)平均為8個(gè)，這一結(jié)果和西方大型試驗(yàn)EORTC trial 22921結(jié)果相符[5,16-25]。

以往很多外科醫(yī)師都會(huì)爭(zhēng)論，對(duì)于直腸切除的患者，是否要加上保護(hù)性的橫結(jié)腸或回腸造口以減少吻合口漏的機(jī)率[17]。近年來(lái)，愈來(lái)愈多的臨床結(jié)論逐漸朝向常規(guī)建造保護(hù)性橫結(jié)腸或回腸造口以減少手術(shù)后的并發(fā)癥發(fā)生[18-20]。近期的一篇Meta分析顯示，在結(jié)直腸癌患者中，術(shù)后吻合口漏對(duì)于癌癥的局部復(fù)發(fā)及存活率都有不良的影響[21]。我們的患者若術(shù)前接受過(guò)放化療，術(shù)中會(huì)常規(guī)地建造保護(hù)性橫結(jié)腸或回腸造口，因此我們的早期及晚期手術(shù)并發(fā)癥發(fā)生率都相對(duì)較低。對(duì)于大多數(shù)的患者，在切除直腸后我們都會(huì)建造一個(gè)保護(hù)性的橫結(jié)腸造口，方法是在右上腹壁打開(kāi)一個(gè)切口，再將橫結(jié)腸經(jīng)由此切口拉到體外，用一根軟管穿過(guò)橫結(jié)腸的系膜并固定在皮膚上作為支撐，然后切開(kāi)橫結(jié)腸，用可吸收線將腸壁和皮膚做一整圈的縫合。我們認(rèn)為，不需要在腸道與腹壁間做加強(qiáng)性的縫合，這樣的好處是當(dāng)需要關(guān)閉造口時(shí)，橫結(jié)腸與腹壁的界面比較容易分開(kāi)。之后我們只需要切除一圈橫結(jié)腸黏膜與皮膚的交界即可將橫結(jié)腸縫合關(guān)閉，手術(shù)時(shí)間短且操作簡(jiǎn)單，不需要切除整個(gè)造口以及腸道縫合手術(shù)，術(shù)后并發(fā)癥的發(fā)生率自然較少。除了早期已有復(fù)發(fā)或轉(zhuǎn)移的患者未接受腸造口關(guān)閉手術(shù)，其余的患者都可以關(guān)閉其保護(hù)性腸造口。所以，根據(jù)我們的經(jīng)驗(yàn)，常規(guī)建造保護(hù)性腸造口，不只可以減少手術(shù)后并發(fā)癥的發(fā)生，而且可以保證患者的安全治療。

另外，患者在接受手術(shù)后，由于直腸失去了收納糞便的功能，患者術(shù)后的排便次數(shù)會(huì)明顯增加，生活質(zhì)量也會(huì)受到很大的影響。有研究顯示，術(shù)前放療對(duì)于術(shù)后肛門括約肌功能的恢復(fù)會(huì)有影響[22]。我們的經(jīng)驗(yàn)顯示，在患者接受腸道造口關(guān)閉手術(shù)后的第1個(gè)月，只有約1/3的患者能有滿意的大便次數(shù)(每天約1～4次，且無(wú)明顯失禁)；但在造口關(guān)閉2年后，近90%的患者有滿意的大便次數(shù)。換句話說(shuō)，每天的排便次數(shù)會(huì)隨著時(shí)間而改善，大約在術(shù)后2年時(shí)達(dá)到穩(wěn)定狀態(tài)[23]。

從1998年至今，成功大學(xué)附屬醫(yī)院的低位以及局部侵犯較嚴(yán)重的直腸癌患者，大多都可接受完整的放療及化療，在治療6至8周后再接受手術(shù)治療。截至2009年，有21%接受術(shù)前放化治療的患者達(dá)到了病理腫瘤細(xì)胞完全緩解，將近50%的患者腫瘤可以縮小一半以上，且只有1.6%的患者有三級(jí)以上的放射或化療毒性反應(yīng)。約90%的術(shù)后患者會(huì)接受為期六個(gè)月的術(shù)后輔助化療。長(zhǎng)期追蹤的結(jié)果顯示患者5年存活率達(dá)到83.6%，5年無(wú)癌復(fù)發(fā)存活率達(dá)到69.3%，局部癌癥復(fù)發(fā)率達(dá)到3%。我們的結(jié)果和其他同樣使用術(shù)前放射及化學(xué)治療的前瞻性試驗(yàn)結(jié)果相同[24]。大多數(shù)的試驗(yàn)都能達(dá)到8%～20%的病理腫瘤細(xì)胞完全緩解率，少數(shù)報(bào)告可達(dá)到30%的病理腫瘤細(xì)胞完全緩解率[25-26]，這是因?yàn)樵囼?yàn)通常加入了更強(qiáng)的化療或靶向藥物，治療的同時(shí)會(huì)增加并發(fā)癥的發(fā)生，也會(huì)使患者不愿意繼續(xù)接受治療。

綜上所述，成功大學(xué)附屬醫(yī)院結(jié)直腸癌治療團(tuán)隊(duì)的經(jīng)驗(yàn)顯示，針對(duì)低位直腸癌患者，術(shù)前放射及化學(xué)治療可以達(dá)到較好的病理腫瘤細(xì)胞緩解率，又因?yàn)槎拘暂^低，患者都能承受完整的治療過(guò)程。此方法即在放射治療后的6至8周行直腸全系膜切除術(shù)及保護(hù)性橫結(jié)腸造口手術(shù)，可以保證高質(zhì)量手術(shù)的實(shí)施，有利于癌癥的局部控制、減少患者的痛苦。

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李政昌.低位直腸癌的治療[J/CD].中華結(jié)直腸疾病電子雜志，2013，2(5)：214-216.

Thetreatmentoflowrectalcancer

LIZheng-chang

DivisionofColorectalSurgery,DepartmentofSurgery,NationalChengKungUniversityHospital,CollegeofMedicine,NationalChengKungUniversity,Tainan70403,Taiwan

Correspondingauthor:LIZheng-chang，Email:leejc@mail.ncku.edu.tw

Since 1998,the multidisciplinary team of colorectal cancer started to perform neoadjuvant radiochemotherapy for lower rectal cancer.For every patient who completed the neoadjuvant radiochemotherapy treatment course,total mesorectal excision with defunctioning colostomy or ileostomy would be done.After completion of post-operative adjuvant chemotherapy,the defunctioning colostomy or ileostomy would be closed surgically.We presented our treatment results here.

Rectal neoplasms； Proctocolectomy，restorative； Radiotherapy dosage； Drug therapy，combination

10.3877/cma.j.issn.2095-3224.2013.05.01.

70403 臺(tái)南，成功大學(xué)醫(yī)學(xué)院附設(shè)醫(yī)院外科部(Email：Leejc@mail.ncku.edu.tw)

2013-08-15)

(本文編輯：陳瑛罡)