Article(id=1199337299759694228, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199337298941804946, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2689.2023.0510, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1672416000000, receivedDateStr=2022-12-31, revisedDate=null, revisedDateStr=null, acceptedDate=1676217600000, acceptedDateStr=2023-02-13, onlineDate=1763873894872, onlineDateStr=2025-11-23, pubDate=1706371200000, pubDateStr=2024-01-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1763873894872, onlineIssueDateStr=2025-11-23, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1763873894872, creator=13701087609, updateTime=1763873894872, updator=13701087609, issue=Issue{id=1199337298941804946, tenantId=1146029695717560320, journalId=1189873630562394117, year='2024', volume='49', issue='1', pageStart='1', pageEnd='120', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1763873894677, creator=13701087609, updateTime=1763874094669, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1199338137823572576, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199337298941804946, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1199338137823572577, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1199337298941804946, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=10, endPage=16, ext={EN=ArticleExt(id=1199337300107821466, articleId=1199337299759694228, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Strategic planning for paying attention to anal preservation in low rectal cancer, columnId=1199337300007158168, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issue on Rectal Cancer Surgery and Perioperative Treatment Strategies, runingTitle=null, highlight=null, articleAbstract=

Based on the background of a multidisciplinary treatment team and the increasing high-quality life aspirations of patients, the preservation of anal function for patients with low rectal cancer has undergone changes in recent years. With the optimization of neoadjuvant therapy, refinement of surgical techniques, and the deepening of the concept of anal preservation after surgery, the concept of anal preservation for low rectal cancer has gradually shifted from traditional simple surgery to comprehensive treatment, and anal preservation surgery tends to be more accurate preservation. The goal of comprehensive treatment is to preserve good anal function and reduce surgical damage. However, comprehensive treatment for anal preservation in low rectal cancer is still in its infancy, and there is no consensus on the strategy planning for anal preservation. Therefore, summarizing various preoperative, intraoperative, and postoperative treatment strategies for low rectal cancer is of great significance for the selection of anal preservation schemes for patients with low rectal cancer. This article focus on exploring the optimization of neoadjuvant therapy models, "watch and wait" plans, the development of anal preservation techniques, and postoperative and preservation strategies, aiming to review the current status of anal preservation strategy planning for low rectal cancer.

, correspAuthors=Bo Feng, authorNote=null, correspAuthorsNote=
E-mail:
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基于多学科诊疗模式背景和患者日益增长的高质量生活意愿,近年来低位直肠癌保肛策略发生改变。随着新辅助治疗模式的优化、手术术式的精化以及术后保肛理念的深入人心,低位直肠癌保肛策略逐渐从传统的单纯手术转变为综合治疗,保肛手术也更倾向于精准、极限保肛。综合治疗旨在为患者保留良好的肛门功能,减轻手术损伤。但低位直肠癌保肛综合治疗仍处于新兴发展阶段,对保肛的策略规划尚未达成共识。因此,总结各类低位直肠癌术前、术中、术后的治疗策略,对于低位直肠癌患者保肛方案的选择具有重要意义。本文着重探讨新辅助治疗模式的优化、“观察等待”方案、保肛技术的发展以及术后保肛策略等,旨在对低位直肠癌保肛策略规划的现状进行综述。

, correspAuthors=冯波, authorNote=null, correspAuthorsNote=
冯波,E-mail:
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徐玺谟,硕士研究生,主要从事结直肠癌的基础与临床研究

冯波,主任医师,硕士研究生导师,任上海交通大学医学院附属瑞金医院胃肠外科副主任。担任中华医学会外科学分会结直肠外科学组委员,中国医师协会结直肠肿瘤医师委员会微创解剖学组副主任委员,中国医师协会外科医师分会MDT医师青年委员会副主任委员,中国医师协会结直肠肿瘤医师委员会青委会副主任委员,中国研究型医院学会结直肠肛门外科委员会副主任委员,中国性学会结直肠肛门功能外科分会副主任委员,中国医师协会外科医师分会TaTME专业委员会副主任委员。主持国家自然科学基金、上海市科委等多个研究项目,牵头国内外多个RCT临床研究,以通信作者/第一作者在JAMA Surgery、International Journal of Surgery、Molecular Cancer等杂志发表论文30余篇。荣获教育部科技进步奖一等奖、上海市科技进步奖二等奖、中华医学科学技术奖二等奖、上海医学科技奖一等奖等多项奖项。

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冯波,主任医师,硕士研究生导师,任上海交通大学医学院附属瑞金医院胃肠外科副主任。担任中华医学会外科学分会结直肠外科学组委员,中国医师协会结直肠肿瘤医师委员会微创解剖学组副主任委员,中国医师协会外科医师分会MDT医师青年委员会副主任委员,中国医师协会结直肠肿瘤医师委员会青委会副主任委员,中国研究型医院学会结直肠肛门外科委员会副主任委员,中国性学会结直肠肛门功能外科分会副主任委员,中国医师协会外科医师分会TaTME专业委员会副主任委员。主持国家自然科学基金、上海市科委等多个研究项目,牵头国内外多个RCT临床研究,以通信作者/第一作者在JAMA Surgery、International Journal of Surgery、Molecular Cancer等杂志发表论文30余篇。荣获教育部科技进步奖一等奖、上海市科技进步奖二等奖、中华医学科学技术奖二等奖、上海医学科技奖一等奖等多项奖项。

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重视低位直肠癌保肛策略规划
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徐玺谟 1, 2 , 冯波 1, 2, *
解放军医学杂志 | 直肠癌手术及围手术期治疗策略专题 2024,49(1): 10-16
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解放军医学杂志 | 直肠癌手术及围手术期治疗策略专题 2024, 49(1): 10-16
重视低位直肠癌保肛策略规划
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徐玺谟1, 2, 冯波1, 2, *
作者信息
  • 1上海交通大学医学院附属瑞金医院普外科,上海 200025
  • 2上海市微创外科临床研究中心,上海 200025
  • 徐玺谟,硕士研究生,主要从事结直肠癌的基础与临床研究

    冯波,主任医师,硕士研究生导师,任上海交通大学医学院附属瑞金医院胃肠外科副主任。担任中华医学会外科学分会结直肠外科学组委员,中国医师协会结直肠肿瘤医师委员会微创解剖学组副主任委员,中国医师协会外科医师分会MDT医师青年委员会副主任委员,中国医师协会结直肠肿瘤医师委员会青委会副主任委员,中国研究型医院学会结直肠肛门外科委员会副主任委员,中国性学会结直肠肛门功能外科分会副主任委员,中国医师协会外科医师分会TaTME专业委员会副主任委员。主持国家自然科学基金、上海市科委等多个研究项目,牵头国内外多个RCT临床研究,以通信作者/第一作者在JAMA Surgery、International Journal of Surgery、Molecular Cancer等杂志发表论文30余篇。荣获教育部科技进步奖一等奖、上海市科技进步奖二等奖、中华医学科学技术奖二等奖、上海医学科技奖一等奖等多项奖项。

通讯作者:

冯波,E-mail:
Strategic planning for paying attention to anal preservation in low rectal cancer
Xi-Mo Xu1, 2, Bo Feng1, 2, *
Affiliations
  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • 2Shanghai Clinical Medical Center for Minimally Invasive Surgery, Shanghai 200025, China
出版时间: 2024-01-28 doi: 10.11855/j.issn.0577-7402.2689.2023.0510
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基于多学科诊疗模式背景和患者日益增长的高质量生活意愿,近年来低位直肠癌保肛策略发生改变。随着新辅助治疗模式的优化、手术术式的精化以及术后保肛理念的深入人心,低位直肠癌保肛策略逐渐从传统的单纯手术转变为综合治疗,保肛手术也更倾向于精准、极限保肛。综合治疗旨在为患者保留良好的肛门功能,减轻手术损伤。但低位直肠癌保肛综合治疗仍处于新兴发展阶段,对保肛的策略规划尚未达成共识。因此,总结各类低位直肠癌术前、术中、术后的治疗策略,对于低位直肠癌患者保肛方案的选择具有重要意义。本文着重探讨新辅助治疗模式的优化、“观察等待”方案、保肛技术的发展以及术后保肛策略等,旨在对低位直肠癌保肛策略规划的现状进行综述。

低位直肠癌  /  保肛手术  /  新辅助治疗  /  观察等待

Based on the background of a multidisciplinary treatment team and the increasing high-quality life aspirations of patients, the preservation of anal function for patients with low rectal cancer has undergone changes in recent years. With the optimization of neoadjuvant therapy, refinement of surgical techniques, and the deepening of the concept of anal preservation after surgery, the concept of anal preservation for low rectal cancer has gradually shifted from traditional simple surgery to comprehensive treatment, and anal preservation surgery tends to be more accurate preservation. The goal of comprehensive treatment is to preserve good anal function and reduce surgical damage. However, comprehensive treatment for anal preservation in low rectal cancer is still in its infancy, and there is no consensus on the strategy planning for anal preservation. Therefore, summarizing various preoperative, intraoperative, and postoperative treatment strategies for low rectal cancer is of great significance for the selection of anal preservation schemes for patients with low rectal cancer. This article focus on exploring the optimization of neoadjuvant therapy models, "watch and wait" plans, the development of anal preservation techniques, and postoperative and preservation strategies, aiming to review the current status of anal preservation strategy planning for low rectal cancer.

low rectal cancer  /  anal preservation surgery  /  neoadjuvant therapy  /  watch and wait
徐玺谟, 冯波. 重视低位直肠癌保肛策略规划. 解放军医学杂志, 2024 , 49 (1) : 10 -16 . DOI: 10.11855/j.issn.0577-7402.2689.2023.0510
Xi-Mo Xu, Bo Feng. Strategic planning for paying attention to anal preservation in low rectal cancer[J]. Medical Journal of Chinese People’s Liberation Army, 2024 , 49 (1) : 10 -16 . DOI: 10.11855/j.issn.0577-7402.2689.2023.0510
直肠癌是消化道最为常见的恶性肿瘤之一,我国直肠癌发病率和死亡率分别居全球恶性肿瘤第4、5位,且呈现年轻化和发病率上升的趋势[1]。医学上通常将距肛缘5 cm以内的直肠癌归类为低位直肠癌[2]。由于低位直肠癌保肛手术存在较高的复杂性和挑战性,对其策略规划的研究一直备受关注。然而,随着直肠癌术前分期评估方法的改进、新辅助治疗模式的不断优化以及多种低位直肠癌保肛手术的广泛应用,低位直肠癌保肛率已经逐渐增高,目前已达到50%~79%[3-6]。因此,低位直肠癌保肛的综合治疗需得到充分的关注,对低位直肠癌保肛的策略规划也亟需统一。本文全面总结低位直肠癌保肛策略规划的现状,着重探讨新辅助治疗模式的优化、“观察等待”策略以及保肛技术的发展,以期为低位直肠癌患者保肛方案的选择提供借鉴。
近年来,随着多学科团队(multi-disciplinary team,MDT)在结直肠癌综合诊断和治疗方面的努力,直肠癌的治疗水平不断提升。局部进展期直肠癌(locally advanced rectal cancer,LARC)局部复发和远处转移的发生率较高,是MDT诊治的重点和难点。新辅助治疗可显著提高手术切除率,提供保肛机会,甚至达到病理完全缓解(pathological complete response,pCR)或临床完全缓解(clinical complete response,cCR),降低局部复发率,是LARC治疗的重大突破[7]。因此亟需结合国内外先进经验,对新辅助治疗模式进行优化和探索,以提高国内低位直肠癌保肛治疗的综合水准。
目前针对LARC治疗的主流模式,通常是长程放化疗联合全直肠系膜切除术(total mesorectal excision,TME),术后辅助为期3~6个月的化疗[8-9]。这一治疗模式虽然显著提高了R0切除率,降低了局部复发风险并增加了保肛机会,但其缺点也逐渐显现:(1)长程放化疗耗时5周,部分患者因不良反应较大而难以耐受,且pCR率仅为10%~20%,仅能降低局部复发率,无法改善生存;(2)放化疗后6~8周才可达到显著的肿瘤退缩,从发病至手术的时间间隔超过3个月,未能及时进行全身化疗,对于部分患者有导致肿瘤复发的风险;(3)手术并发症较多,常需行保护性造口,且需于辅助化疗结束后方可行造口回纳;(4)由于手术并发症和患者体力等因素,辅助化疗往往不能及时开展,增加了肿瘤复发转移的风险。相比之下,欧洲各国一直将术前短程放疗(5 Gy×5)作为直肠癌术前放化疗的标准模式之一,其优势在于显著缩短了放疗时间,局部控制及总生存期(overall survival,OS)均与长程同步放化疗无明显差异[8-9],但放疗后1周即进行手术治疗,此时原发肿瘤尚未明显退缩,pCR率较低。而长程放化疗6~8周后进行手术,在5-氟尿嘧啶(5-fluorouracil,5-FU)/卡培他滨协同增敏的情况下,可充分展现放疗对局部晚期直肠癌缩瘤降期的效果,pCR率常达10%以上,并可改善R0切除率和保肛率[10]
为提高低位直肠癌的治疗效果,国内外学者不断对短程放疗进行探索优化。由于延长放疗与手术的间隔期可提高pCR率,Stockholm 临床研究对短程放化疗后立即手术与延期6~8周手术的疗效进行对比,结果显示,后者的pCR率由0.5%提高至12.5%,两组具有相似的局部复发率、远处生存率和总生存率[11]。STELLAR试验也探讨了LARC短程放疗的疗效:研究组(n=298)首先行短程放疗(25 Gy/5Fx),后行CAPOX方案化疗4个周期;对照组行长程同步放化疗(50 Gy/25Fx)同步卡培他滨,放疗后6~8周进行手术,两组术后再分别给予2或6个周期CAPOX化疗。结果显示,研究组3年无病生存率为64.5%,非劣效于对照组的62.3%(P<0.001)。进一步亚组分析显示,研究组的(pCR+cCR)率、3年总生存率均明显高于对照组(22.5% vs. 12.6%,P=0.001;86.5% vs. 75.1%,P=0.001)[12]。以上研究结果表明,短程放化疗联合其他治疗方式,可作为低位直肠癌的有效治疗策略之一,为临床治疗提供了新的思路和选择。
长期以来,直肠癌手术前同步放化疗的首选药物为5-FU或卡培他滨[13],相较于单纯放疗,这些药物可显著增强放疗的敏感性,降低局部复发率及肿瘤临床分期,但无法延长OS。为进一步提高治疗效果,一些期临床研究在卡培他滨的基础上,每周同步加用奥沙利铂[14-19]或伊立替康[20]增敏。尽管有部分研究发现pCR率有所提高,但多数研究未能复制这些结果。因此,目前在长期同步放化疗中,5-FU或卡培他滨仍是放疗增敏的“最佳搭档”。
随着MDT模式的发展,结直肠癌的治疗策略逐渐向个性化治疗转变。为了提高术前治疗效果,降低术后复发率和提高保肛率,越来越多的靶向药物和免疫药物被应用于直肠癌新辅助放化疗。表皮生长因子单克隆抗体西妥昔单抗与其配体结合后可阻断RAS/RAF/MAPK通路的活化,从而抑制肿瘤生长。化疗联合西妥昔单抗可进一步提高疗效,多项研究表明,新辅助放化疗联合西妥昔单抗可明显提高RAS野生型局部晚期直肠癌患者的pCR率和局部控制率[21-22]。贝伐珠单抗是一种针对人血管内皮细胞生长因子的单克隆抗体,可抑制肿瘤血管生成,从而抑制肿瘤生长。此外,贝伐珠单抗还可改善肿瘤组织毛细血管通透性,重塑血管床,促进化疗药物对肿瘤组织的渗透。贝伐珠单抗联合化疗是RAS突变型转移性结直肠癌的一线用药。Dutch-M1研究表明,进展期直肠癌采用贝伐珠单抗联合新辅助放化疗治疗的cCR率和准pCR率分别达到26%和16%,2年生存率可达到80%,提示在新辅助治疗背景下,联合使用贝伐珠单抗和化疗可显著提高治疗效果,为低位直肠癌患者的保肛提供了可能[23]。近年来,免疫检查点阻断治疗(immune checkpoint blockage,ICB)在结直肠癌治疗中显示出巨大的潜力,针对程序性死亡受体1(programmed cell death 1,PD-1)及其配体(programmed cell death 1 ligand 1,PD-L1)的治疗在一系列临床试验中展现出较好的效果。多项研究证实,抗PD-1治疗可使31.1%~71.0%的高度微卫星不稳定(microsatellite instability-high,MSI-H)或错配修复缺陷(deficient mismatch repair,dMMR)直肠癌患者达到CR或PR[24-26],这为低位直肠癌患者提供了潜在的保肛可能。
随着多学科治疗模式的发展,为促进直肠癌的肿瘤退缩,提高pCR率和R0切除率,以及降低远处转移的风险,当前有趋势将直肠癌的辅助化疗完全提至术前,即TNT。TNT主要分为巩固化疗和诱导化疗,分别是在同步放化疗后在TME前或同步放化疗前进行。
部分研究表明,巩固化疗可进一步提高直肠癌患者的pCR率和无病生存率,从而降低肿瘤复发的风险。如Marco等[27]研究发现,在同步放化疗后进行0、2、4和6个周期的mFOLFOX6方案巩固化疗的4组直肠癌患者的pCR率分别为20%、23%、26%和37%,不同治疗组间的无病生存率差异有统计学意义(P=0.004);而诱导化疗则可提高直肠癌患者的pCR率、无病生存率和无远处转移生存率,从而进一步降低肿瘤复发和远处转移的风险。如PRODIGE 23试验评估了诱导化疗对LARC的作用,该研究试验组采用mFOLFIRINOX(CF/5-FU+伊立替康+奥沙利铂三药联合)方案化疗6次后,行TME及长程同步放化疗,对照组先接受同步长程放化疗,然后在TME术后进行辅助化疗,辅助化疗时间试验组为3个月,对照组为6个月,结果显示,试验组的pCR率(27.8% vs. 12.1%,P<0.001)、无病生存率(75.7% vs. 68.5%,P=0.034)和无远处转移生存率(78.8% vs. 71.7%,P=0.017)均明显高于对照组,从另一方面验证了TNT模式的疗效[28]。综上,TNT治疗直肠癌疗效显著,对提高直肠癌患者的pCR率以及降低复发和远处转移风险具有重要意义。
为达到尽可能高的病理有效应答率或保肛率,笔者认为,现阶段的新辅助治疗策略应有如下要求:(1)灵活运用短程放疗,提高pCR率。(2)随着化疗±靶向/免疫治疗的发展,有充分依据将其用于围放疗期,以进一步提高放疗疗效。(3)尽量采用TNT,一方面实现最大程度的缩瘤降期,提高R0切除率和保肛率;另一方面可避免因手术并发症或体力虚弱所导致的辅助化疗的延误,还能尽早回纳造口,提高患者生活质量。
对于接受新辅助治疗后达到cCR的患者,根治性切除术可能导致过度医疗。在保证根治的前提下,最大限度地减少对肛门功能的影响,提高患者生活质量,是目前直肠癌治疗追求的目标,因此,基本不影响功能的“观察等待”策略受到越来越多的关注和重视,目前的理念也逐渐从传统的“一刀切”转变为“不开刀”。
“观察等待”方案是一种非标准的治疗方案,但随着TNT的提出,其在新辅助治疗后获得cCR的直肠癌患者中得到了广泛的应用。该方案是指在术前或新辅助治疗后出现完全缓解时不立即进行手术,而是选择观察和等待。2004年Habr-Gama等[29]开创性地提出了这一方案,研究发现,接受“观察等待”方案的cCR直肠癌患者是安全有效的,5年总生存率达到100%,5年无病生存率为92%[30]。同时,一项前瞻性随机对照研究发现,“观察等待”策略可在不影响生存率的情况下更好地保留患者的肛门(2年无病生存率>70%,器官保留率>40%),提高患者的生活质量[31]。据报道,97%接受“观察等待”方案的患者局部复发发生于cCR的前2年,且局限于肠壁[32]。对于发生肿瘤再生的患者,83.8%~95.4%的复发患者仍可行挽救手术[33-34],且82.0%~92.0%的患者可保留肛门,其生活质量不受影响[35-36]。然而,目前缺乏高质量的前瞻性数据来评估“观察等待”方案对患者远期生存的影响。有研究报道,在接受新辅助放化疗的488例直肠癌患者中,术前19%被诊断为cCR,但术后仅有10%的患者最终诊断为pCR[37],提示“观察等待”方案存在潜在的较高的复发率和转移率。因此对于“观察等待”方案,密切随访必不可少。
基于以上研究,笔者认为,对新辅助治疗后达到cCR的患者可在充分知情同意和密切随访的前提下,对部分患者尝试“观察等待”方案,从而最大程度地保留肛门功能。
TME是直肠癌的标准术式,但对于低位直肠癌,TME术式由于骨盆本身的解剖结构以及腔镜的刚性结构而存在一定的技术难度[38]。随着解剖学、医学影像学的发展,外科医师对盆腔结构的理解逐渐加深,近年来直肠癌保肛手术治疗策略发生了变化,更多的经肛手术应用于临床,低位直肠癌患者精准保肛乃至极限保肛成为可能。
经肛腔镜局部切除术包括经肛门内镜显微手术(transanal endoscopic microsurgery,TEM)和经肛门微创手术(transanal minimally invasive surgery,TAMIS)[39-40]。经肛腔镜局部切除术是早期直肠癌(T1期)的适应证[41-43]。随着直肠癌多学科治疗模式的建立,术前新辅助放化疗成为治疗进展期直肠癌的重要策略之一。经过新辅助放化疗后,低位直肠癌患者出现显著降期,甚至达到cCR,为肿瘤局限于肠壁的患者提供了“以点代面”的局部切除治疗方案,如经肛腔镜局部切除术。González等[44]认为,对于新辅助放化疗后ypT0-1的进展期直肠癌患者,选择经肛腔镜局部切除术可达到与根治性手术相似的肿瘤学疗效。Borschitz等[45]的研究显示,ypT0(局部复发率0%)和ypT1(局部复发率2%)是直肠癌预后的保护因素,而ypT2患者术后局部复发率明显增高(6%~20%)。直肠肿瘤TAMIS术后的局部复发率为2.7%,而TEM术后为2%~16%,两种手术方式的远期疗效相似,且在低位直肠癌患者中安全可行[9,42-43,46]
笔者根据本中心的经验及国外的研究报道,认为针对接受新辅助治疗后达到ypT0-1且有保肛意愿的低位直肠癌患者,可考虑作为扩大经肛腔镜局部切除术的适应证[47]
ISR是一种针对极低位直肠癌的保肛手术,可部分或完全切除内括约肌及直肠纵肌,实现拓展直肠远端切缘至肛缘,并以手工吻合或器械吻合形式行结肛吻合。自1994年提出以来,ISR被认为是极限保肛的“最后一道防线”[48]。随着新辅助治疗的广泛应用和微创技术的发展,ISR在临床上的应用策略也发生了改变。有研究发现,新辅助治疗后,ISR组(经过倾向性评分匹配)与腹会阴切除术(abdominoperineal resection,APR)组5年总生存率(89.5% vs. 76.7%,P=0.056)、5年无病生存率(76.3% vs. 57.8%,P=0.080)和5年无局部复发生存率(90.8% vs. 79.2%,P=0.103)差异无统计学意义[49],提示新辅助治疗后行ISR的患者肿瘤学结局与行APR的患者无明显差异,且ISR能够保留肛门,保证患者的生活质量。但ISR术后患者具有短期较重的肛门功能障碍。一项系统性综述显示,ISR术后出现大便失禁、排气失禁、排便急迫症状者分别占29.1%、23.8%、18.6%[50]。然而多数低位直肠癌患者ISR术后肛门功能可在6~12个月逐渐改善,最后趋于稳定[51-52]。因此,笔者认为,即使将手术适应证扩大到T3-T4期低位直肠癌,对新辅助治疗反应较好的低位直肠癌患者行ISR仍是安全的,可获得良好的肿瘤学结局和功能学结局。
TaTME是一种针对低位直肠癌的新兴技术,自2010年提出以来备受关注[53],该技术可实现精准保肛,且“自下而上”的独特入路尤其适用于肥胖、低位及超低位直肠癌、狭窄骨盆等困难病例。作为一项新兴技术,TaTME的近远期疗效亟待证实。目前多项研究已确定TaTME术式的近期疗效。Yao等[54]的全国TaTME多中心登记注册研究结果显示,1283例TaTME患者术中中转率为2.4%,术后并发症发生率为18.4%,吻合口漏发生率为5.8%。同样,Liu等[55]的TaLaR研究结果显示,TaTME组与腹腔镜TME组的近期疗效无明显差异。上述研究结果提示,TaTME术式应用于低位直肠癌的治疗安全可靠,其近期疗效与腹腔镜TME相当。但需要注意的是,由于对“自下而上”入路经验的缺乏和较长的学习曲线,一些不良事件的发生风险较高[56-58]。一项多中心回顾性研究结果显示,接受结构化培训后,前10例TaTME术后并发症尤其是吻合口漏发生率较后10例高,且病理结果较后10例差[59],提示目前的结构化培训仍需精进。目前尚缺乏TaTME术式的远期结局研究,且由于荷包缝合过程中可能导致肿瘤细胞泄漏,该技术存在一定的局部复发风险。例如,挪威、荷兰等国均报道TaTME术后较多患者发生多灶性局部复发,并暂停了TaTME技术的应用,这为外科医师敲响了警钟[60-61]。而国际性前瞻性随机对照研究COLOR 及TaLaR研究正在进行中。笔者认为,虽然经历了10多年的曲折发展,目前的研究表明TaTME术式是安全有效的,对于肥胖、低位和超低位直肠癌、狭窄骨盆等患者可能获益更多。外科医师需接受规范的结构化培训,熟练掌握TaTME技术后谨慎开展。相信随着高质量前瞻性对照研究的开展,TaTME的疗效将进一步得到证实,使更多低位直肠癌患者免受永久性造口的痛苦。
综上,随着新辅助治疗的发展,目前对于低位直肠癌保肛手术的策略有较大变化,从传统的Dixon术式或Hartman二期手术逐渐转变为“不开刀”“开小刀”及“经肛开”。对于新辅助治疗后达到cCR的患者,若保肛意愿极为强烈,可在密切随访下采用“观察等待”策略;对于ypT0-1期及“观察等待”后肿瘤复发的患者,可采取经肛腔镜局部切除术;对于肿瘤位置极低伴狭窄骨盆的患者,可采取ISR或TaTME术式精准保肛。
随着新辅助放疗和保肛手术的发展,术后保肛策略愈加重要。放疗可导致盆腔神经损伤和盆腔组织纤维化,已被确认为低位直肠癌术后低位前切除综合征(low anterior resection syndrome,LARS)的独立危险因素[62-63]。由于肿瘤位置低,预防性回肠造口在术中越来越常见,然而预防性回肠造口后吻合口长期没有粪便通过,回纳后易发生LARS甚至吻合口废用性狭窄[64-65]。因此,外科医师不仅要对低位直肠癌患者术前以及手术做好安排,术后更要统筹兼顾,以免前功尽弃。目前认为,术后应尽早、规范开始肛门功能康复锻炼,如提肛运动等。一项多中心随机对照试验显示,直肠癌保肛术后患者进行12周的盆底肌肉训练后,术后第4、6个月LARS症状分级较未训练组轻[66]。此外,造口回纳时间也与术后LARS的发生有关。研究发现,术后6个月是患者的窗口期,在此期间回纳造口有利于肛门功能恢复,可降低LARS的严重程度[67]
伴随着新辅助治疗模式、手术方式的不断优化,低位直肠癌精准保肛乃至极限保肛已成为可能。外科医师应对低位直肠癌患者术前、术中、术后的保肛策略进行统筹规划。然而目前低位直肠癌保肛综合治疗在实践上仍属于探索阶段,部分新兴术式的肿瘤学等临床证据尚不充分。未来期待开展更多相关的临床研究以获得高级别的循证医学证据,使更多的低位直肠癌患者获益。
  • 转化医学国家重大科技基础设施(上海)开放课题项目(TMSK-2021-503)
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2024年第49卷第1期
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doi: 10.11855/j.issn.0577-7402.2689.2023.0510
  • 接收时间:2022-12-31
  • 首发时间:2025-11-23
  • 出版时间:2024-01-28
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  • 收稿日期:2022-12-31
  • 录用日期:2023-02-13
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Translational Medicine Program of Major National Science and Technology Infrastructure(TMSK-2021-503)
转化医学国家重大科技基础设施(上海)开放课题项目(TMSK-2021-503)
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    1上海交通大学医学院附属瑞金医院普外科,上海 200025
    2上海市微创外科临床研究中心,上海 200025

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2种不同金属材料的力学参数

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种数
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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