摘要
结直肠癌是最常见的恶性肿瘤之一,在我国其发病率和死亡率均逐年上升。2018年,结直肠癌研究领域在肿瘤的筛查和治疗方面均有进展,主要体现在:(1)筛查:我国首次将多靶点粪便基因检测作为推荐的筛查技术写入专家共识;肠镜做为肠癌筛查的核心技术,其对于右侧肠癌的筛查意义也得到进一步的支持,伴随着人工智能技术在肠镜检查中的应用,其筛查的效率和准确度都将大大提高;以循环肿瘤细胞为代表的新的筛查技术和以分子遗传学为基础的个体化筛查方案是未来发展的方向。(2)治疗方面:手术作为结直肠癌治疗的核心,从技术角度来说已经相当成熟,传统腹腔镜手术已经成为结直肠癌手术优先选择,无论开放手术、机器人手术、单孔腹腔镜手术,均未发现优于多孔腹腔镜手术。外科学家的研究重心是精准地选择手术方式和保护并改善功能,比如为了减少新辅助放疗后直肠癌手术患者的并发症和改善生活质量,笔者团队提出的"天河术"等。化疗作为结直肠癌治疗的基础,在多方面都展现了良好的效果,对于局限于腹膜转移的结直肠癌,在高质量的肿瘤减灭术后,全身系统的化疗更为重要;而在此基础上,腹腔热灌注化疗并未带来明显的生存获益,反而增加了术后并发症的风险。FOLFOX方案(奥沙利铂、氟尿嘧啶)化疗达到了与新辅助放化疗相似的3年无病生存率(DFS),对放疗的临床价值提出了挑战。虽然多项研究证实,全程新辅助化疗(TNT)可以提高结直肠癌患者的病理完全缓解率(pCR)和DFS,但化疗也并不能一味地向扩大化发展,如何综合患者临床特征和分子生物学标记物筛选出需要化疗的高危人群,以及根据患者基因特征个体化用药,也是目前的研究热点。免疫治疗作为肿瘤学的颠覆者正在改变结直肠癌诊疗的各个方面:为了适应免疫治疗,重新修订了实体肿瘤疗效评估标准——iRECIST,免疫评分也有望重新定义肿瘤临床分期体系,无论是针对晚期肿瘤的CheckMate-142研究和早期肿瘤新辅助治疗的NCT03026140研究,都取得了喜人的结果。虽然靶向表皮生长因子受体和血管内皮生长因子的治疗未看到明显的新进展,但是新的靶向药物如Eltanexor(ETLA、KPT-8602)和cobimetinib(MEK抑制剂)已经在临床研究中观察到了很好的疗效。根据患者肿瘤相关信号通路检测结果,跨指南选择靶向药物治疗也是研究的方向。虽然IWWD研究结果给"等待-观察"策略不小的打击,但随着TNT方案的探索、更精确的影像学疗效评估以及免疫治疗的应用,"等待-观察"策略也将会重新受到重视。近年来我们看到了人工智能技术的蓬勃发展,虽然在医学领域还处于探索阶段,但必将在未来重塑结直肠癌诊疗的各个环节,引领研究的方向。
Colorectal cancer is one of the most common malignant tumors,and its incidence and mortality are increasing year by year in China.In 2018,for the first time,the FIT-DNA test was written into the expert consensus as the recommended screening technology in China.As the core technology of colorectal cancer screening,colonoscopy for right colon cancer is further supported.With the application of artificial intelligence technology in colonoscopy,the efficiency and accuracy of screening will be greatly improved.New screening technologies represented by circulating tumor cell(CTC)and individualized screening programs based on molecular genetics are future directions.As the core of colorectal cancer treatment,surgery has become quite mature.Traditional laparoscopic surgery has become an optimal choice for colorectal cancer surgery.Open surgery,robotic surgery and single-incision laparoscopic surgery have not been found superior to multiport laparoscopic surgery.The focus of surgical research is to precisely select surgical methods,and to protect normal physiological function of patients.For example,in order to reduce complications and improve quality of life in patients undergoing rectal cancer surgery after neoadjuvant radiotherapy,the "Tianhe surgery" was invented by the authors’ team.Chemotherapy as the basis of colorectal cancer treatment has shown good results in many aspects: The PRODIGE-7 trial has confirmed that systemic chemotherapy is more important for colorectal peritoneal metastasis after high quality cytoreductive surgery(CRS).While the addition of hyperthermic intraperitoneal chemotherapy(HIPEC)with oxaliplatin does not result in the better overall survival(OS),but increases the risk of postoperative complications.The FOWARC study has found that the FOLFOX regimen(oxaliplatin and fluorouracil)achieved a 3-year disease-free survival(DFS)rate similar to that of neoadjuvant chemoradiotherapy,challenging the clinical value of radiotherapy.Although several studies have confirmed that total neoadjuvant therapy(TNT)can improve pathological complete response(pCR)rate and DFS of patients with colorectal cancer,we do not recommend unretricted expansion of chemotherapy.How to combine the clinical characteristics and molecular biological markers to select high-risk groups for chemotherapy,and how to use personalized medicine according to the genetic characteristics of patients,are also hot spots of current research.Immunotherapy is a game-changer in all aspects of colorectal cancer.In order to adapt to the immune therapy,the efficacy evaluation standard of solid tumors(iRECIST)has been revised.Immune score could redefine tumor clinical staging system.Both the Checkmate-142 study for advanced tumors and the NCT03026140 study on neoadjuvant treatment for early tumors showed promising results.Although no significant progress has been seen in the EGFR-targeted therapy and VEGFR-targeted therapy,new targeted drugs such as Eltanexor(ETLA,kpt - 8602)and cobimetinib(MEK inhibitor)have been found to be effective in clinical studies.According to the detection results of tumor-related signaling pathways in patients,cross-guidance selection of targeted drug therapy is also the direction of research.Although the IWWD research results give a big blow to the "watch and wait" strategy,with the exploration of TNT plan,more accurate imaging efficacy evaluation and the application of immunotherapy,the "watch and wait" strategy will also receive new attention.In recent years,we have seen the rapid development of artificial intelligence technology.Although it is still in the exploratory stage in the field of medicine,it will certainly reshape all aspects of colorectal cancer diagnosis and treatment in the future,leading the research direction.
作者
蔡建
王磊
Cai Jian;Wang Lei(Department of Colorectal Surgery,the Sixth Affiliated Hospital, Sun Yat-sen University,Guangzhou 510655,China)
出处
《中华胃肠外科杂志》
CAS
CSCD
北大核心
2019年第1期9-16,共8页
Chinese Journal of Gastrointestinal Surgery
基金
科技部支撑计划[结直肠重大疾病关键诊疗技术研究(2014BA109806)]
国家自然科学基金[TGF-β调控VEGF介导血管新生平衡紊乱在慢性放射性肠炎纤维化中的作用及其分子(81573078)].
关键词
结直肠肿瘤
筛查
手术
化疗
免疫治疗
靶向药物
人工智能
Colorectal neoplasms
Screening
Surgery
Chemotherapy
Immunotherapy
Targeted drugs
Artificial intelligence
作者简介
通信作者:王磊,Email:wang19@mail.sysu.edu.cn,电话:020—38254052.
