摘要
对于新辅助放化疗(nCRT)后达到临床完全缓解(cCR)或近cCR的中低位直肠癌患者,如何在不显著降低肿瘤学预后的同时尽可能保留肛门功能成为医生和患者共同关注的焦点。本研究探讨在cCR或近cCR的直肠癌患者中使用局部切除术作为保留肛门的方法的安全性与可行性。
回顾性分析2014年3月—2023年7月在中国医学科学院北京协和医院51例nCRT后达到cCR或近cCR并行局部切除术的中低位直肠癌患者的临床特征、影像学和病理学表现、手术结果、肿瘤学和功能结果。
51例患者中男性34例,女性17例;平均年龄(61±14)岁。nCRT前影像学分期cT1~2N0 12例(23.5%)、cT3N0 13例(25.5%)、cT1~3N0~1 19例(37.4%),cT1~3N2 7例(13.7%);肿瘤平均距肛门距离为(4.5±1.1)cm。nCRT后均达到cCR或近cCR,并接受了局部切除手术,其中40例(78.4%)行经肛门内镜显微手术(TEM)、7例(13.7%)行经肛门微创手术(TAMIS),4例(7.8%)行传统经肛门局部切除术。术后并发症发生率为27.5%(14/51),其中Clavien-Dindo并发症分级Ⅰ级比例为71.4%。术后组织学显示,ypT0 26例(51.0%),ypT1 8例(15.7%),ypT2 16例(31.4%),ypT3 1例(2.0%);病理结果与术前影像一致率为54.9%。中位随访时间60(34~79)个月,观察到4例(7.8%)局部复发、12例(23.5%)远处转移和5例(9.8%)因病死亡。术后6个月时Wexner评分和低位前切除综合征(LARS)评分均较nCRT后明显下降[Wexner:1(0~2)vs. 2(1~5);LARS:3.3±5.75 vs. 4.3±6.86,均P<0.01]。
全直肠系膜切除术是Ⅱ~Ⅲ期直肠癌标准的手术方
局部切除术通常应用于直肠良性肿瘤或T1N0直肠
本研究对51例在nCRT后评估临床分期为cCR或近cCR,并在北京协和医院基本外科接受了肿瘤局部切除术的中低位直肠癌患者进行回顾性分析,以探索其安全性、肿瘤学及功能学结果,为指导患者诊断和治疗提供参考。
对2014年3月—2023年7月在北京协和医院进行nCRT后经评估为cCR或近cCR,接受局部切除术的直肠癌患者进行回顾性分析。纳入标准:⑴ 经组织学证实为直肠腺癌;⑵ 影像学证实无远处转移(distant metastase,DM);⑶ 肿瘤距离肛门外缘≤10 cm;⑷ nCRT后6~8周再次评估肿瘤cCR或近cCR;⑸ 患者充分了解根治性手术、“W&W”策略、局部切除术风险及收益后,选择行局部切除术。排除标准:患者人口学信息、临床和病理特征、影像学结果、化疗和放疗方案、手术结果、肿瘤学结果、生活质量等资料不全及失访患者被排除在本次分析之外,最终纳入51例患者。
cCR或近cCR标准参考《直肠癌新辅助治疗后等待观察策略专家共识(2020版)
所有患者在放疗完成后8~12周在全身麻醉下进行局部切除术。具体手术方式包括经肛门内镜显微手术(transanal endoscopic microsurgery,TEM

图1 TEM手术过程 A:电刀标记切除范围;B:完整切除直肠病变;C:缝合创面;D:切除后的标本
Figure 1 Procedure of TEM A: Electrocautery marking of the resection margin; B: Complete resection of the rectal lesion; C: Suturing of the wound; D: Resected specimen

图2 患者治疗流程
Figure 2 The process of treatment
主要终点为肿瘤复发,包括局部复发(local recurrence,LR)(管腔或直肠系膜中的肿瘤复发)及DM(非直肠及系膜的其他器官或组织中的转移)。次要终点为:无病生存(disease-free survival,DFS)、总生存(overall survival,OS)和肛门功能。DFS定义为没有肿瘤复发和因病死亡,OS定义为没有因肿瘤原因死亡。随访时间为手术日期到终点事件或最后1次随访日期。
手术后2~3周患者在门诊进行复查,医师将进行DRE并记录术后短期并发症(创面愈合不良、直肠穿孔、创面出血、盆腔感染等)。而后按术后2年内每3个月随访1次,2~5年内每半年随访1次,5年后每年随访1次的频率进行直肠癌常规随
研究共纳入51例患者,其中男性34例,女性17例;平均年龄为(61±14)岁;平均体质量指数(BMI)为(24.90±2.93)kg/
肿瘤分期 | nCRT前影像分期 | nCRT后影像分期 | 手术后病理分期 |
---|---|---|---|
T分期 | |||
0 | 0(0.0) | 22(43.1) | 26(51.0) |
1 | 2(3.9) | 15(29.4) | 8(15.7) |
2 | 21(41.2) | 14(27.5) | 16(31.4) |
3 | 28(54.9) | 0(0.0) | 1(2.0) |
N分期 | |||
0 | 25(49.0) | 51(100.0) | — |
1 | 19(37.3) | 0(0.0) | — |
2 | 7(13.7) | 0(0.0) | — |
TNM分期 | |||
0 | 0(0.0) | 22(43.1) | — |
Ⅰ | 12(23.5) | 29(56.9) | — |
Ⅱ | 13(25.5) | 0(0.0) | — |
Ⅲ | 26(51.0) | 0(0.0) | — |
所有患者均按标准完成了直肠病变完整、全层切除,没有患者中转为根治性手术,其中40例(78.4%)接受TEM术、7例(13.7%)接受TAMIS术、4例(7.8%)接受传统经肛门切除术。平均手术时间(63.5±29.0)min,无术中并发症。所有患者术后6 h可以下床活动,术后第1天可以进食流食。中位术后住院时间3(2~4)d。14例(27.5%)患者出现术后并发症,其中Clavien-Dindo并发症分级Ⅰ级10例(71.4%),其中2例为体温升高,6例为少量便血,2例为血尿;Ⅱ级2例(14.3%),均为尿潴留,予留置尿管后缓解;Ⅲ级2例(14.3%),1例为创面裂开感染,另1例为直肠穿孔,2例均行横结肠造口术。8例患者术后出现肛门疼痛,使用镇痛药物超过3 d。
51例患者中,TRG 0级27例(52.9%)、1级10例(19.6%)、2级13例(25.5%)、3级1例(2.0%)。在判断直肠壁局部肿瘤是否有残留(T分期)方面,病理结果为pT0 26例、pT1 8例、pT2 16例、pT3 1例,与术前影像一致率为54.9%。3例患者底切缘阳性,2例患者侧切缘阳性;2例患者病理提示为黏液腺癌,2例患者病理提示为低分化腺癌。其中1例低分化腺癌且pT2患者、1例侧切缘阳性pT1患者及1例底切缘阳性pT1患者接受了根治手术(
序号 | cT | cN | ycT | ycN | 术后病理 | 浸润深度 | TRG | 侧切缘 | 底切缘 | 根治性手术方案 |
---|---|---|---|---|---|---|---|---|---|---|
1 | 3 | 0 | 1 | 0 | 低分化腺癌 | 2 | 2级 | (-) | (-) | 腹腔镜腹会阴联合直肠癌根治术 |
2 | 0 | 0 | 0 | 0 | 局灶癌变 | 1 | 1级 | (+) | (-) | 腹腔镜腹会阴联合直肠癌根治术 |
3 | 3 | 1 | 2 | 0 | 腺癌 | 1 | 3级 | 0 | 可疑(+) | 腹腔镜腹会阴联合直肠癌根治术 |
中位随访期为60(34~79)个月。4例(7.8%)观察到肿瘤LR,中位至复发时间16(1~26)个月。其中1例患者再次接受了TEM术,术后病理提示为直肠腺瘤;1例患者接受了腹腔镜腹会阴联合直肠癌根治术;1例患者接受盆腔放疗,1例患者同期并发肝、肺转移,化疗后最终导致死亡。12例(23.5%)出现DM,中位至转移时间27.5(13~76)个月。5例(9.8%)因肿瘤死亡,中位至死亡时间54(31~85)个月。3例患者因基础疾病死亡。至随访结束时,所有患者DFS率为64%,OS率为76%(

图3 患者的生存曲线 A:DFS曲线;B:OS曲线
Figure 3 Patient survival curves A: Disease-free survival curve; B: OS curve
治疗前淋巴结阴性的患者有4例发生DM;淋巴结阳性的患者中有8例发生转移(P=0.21)。12例因保肛意愿强烈而行新辅助治疗的Ⅰ期患者中,1例肿瘤复发;39例局部进展期患者中,11例发生肿瘤复发(P=0.30)。26例术后病理分期pT0的患者中有7例发生肿瘤复发(
生存情况 | cCR(n=22) | 近cCR(n=29) | P | pT0(n=26) | 非pT0(n=22 | P |
---|---|---|---|---|---|---|
肿瘤复发 | 7(31.8) | 5(17.2) | 0.23 | 7(26.9) | 5(22.7) | 0.74 |
死亡 | 3(13.6) | 2(6.9) | 0.64 | 2(7.7) | 3(13.6) | 0.65 |
注: 1)除外3例追加根治手术患者
Note: 1) Excluding the 3 patients who underwent additional radical surgery
出院后门诊随访过程中共14例(27.5%)经DRE发现创面裂开,患者主要表现为间断黏液血便、排便次数多,其中1例患者在术后出现大便失禁、2例患者术后出现肛门疼痛、排便困难,Wexner评分达8分。研究中共有4例患者接受了腹会阴联合直肠癌根治术手术,有永久性肠造口。在nCRT后及术后6个月分别对患者进行Wexner评分和LARS评分,nCRT后患者中位Wexner得分2(1~5),术后6个月中位Wexner得分1(0~2)(P<0.01);nCRT后平均LARS评分4.3±6.86,术后6个月平均LARS评分3.3±5.75(P<0.01)。
对于nCRT后判断为cCR的中低位直肠癌患者,器官保留策略越来越多地应用于临床实践,包括“W&W”策略和局部切除术。一些研
既往研
局部切除术作为一种经自然腔道的手术方法,特别是TEM、TAMIS这样的微创手术,具有术中视野清晰、创伤小、术中出血量少,术后恢复快、保留肛门括约肌等优点。但其术后短期内存在肛门疼痛、创面裂开、肛门括约肌功能受损等并发
根据现有指
局部切除术可以去除直肠壁上可能残留的肿瘤病灶。从理论上讲,它有助于更好地局部控制腔内肿瘤的再生。在本研究中,LR率仅为7.8%,DM率23.5%,优于目前所报道的“W&W”策
本研究为单中心的回顾性研究,由于样本量较小,可能存在选择偏倚和混杂偏倚。研究中部分患者对术后辅助推荐治疗方案依从性不佳,可能导致治疗结局存在误差。未来尚需要进行大样本、多中心、随机对照研究来进一步探索局部切除适应证问题及术后远期预后问题。
局部切除术作为一种保留器官、保留功能的手术方法,在nCRT后达到cCR或近cCR的直肠癌患者中有一定的应用价值。它能够整块切除肠壁残留病灶,并判断其病理特征,对于pT0患者可更安全地进行等待观察,使部分患者避免不必要的根治性手术。同时其作为一种微创的治疗方式,具有手术创伤小、术后恢复快、并发症发生少的优势,不仅能够保留直肠,且能够保留肛门功能。但局部切除术并不能替代根治性手术。对nCRT后达到cCR或近cCR的直肠癌患者应仔细评估,当患者难以耐受根治性手术或保留肛门意愿强烈时可谨慎选择局部切除术。
作者贡献声明
邱小原负责完成临床数据收集和统计、文献资料收集分析及文章初稿的写作;周皎琳、陆君阳、牛备战参与数据收集和分析;林国乐、邱辉忠负责指导研究设计、论文写作及修改。全体作者均对文章作出贡献,阅读并同意提交最终版本。
利益冲突
所有作者均声明不存在利益冲突。
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