精准医疗时代低位直肠癌选择性侧方淋巴结清扫价值与策略

随着生物分析技术、基因测序以及大数据分析工具的出现,医学进入了精准医疗时代。临床影像等技术的进步和发展,肿瘤患者术前精准临床分期判断及分子生物学信息的获得使得个体化的精准医疗成为可能,精准医疗时代对直肠癌的诊治提出了新的要求,不同部位的直肠癌治疗方案亦有所差异。手术治疗仍然是当今治疗直肠癌的主要方式,对于侧方淋巴结清扫问题一直存有争议,究其原因侧方淋巴结转移（lateral pelvic lymph node metastasis,LPLM）是全身系统性转移还是局部转移。笔者认为,低位直肠癌诊治应在充分推广诊疗规范的基础上,通过对数据的分析,筛选行侧方淋巴结手术治疗的获益人群,根据精确的诊断分期控制手术指征与范围,减少不必要的创伤及过度治疗从而真正实现精准医疗。     

直肠癌侧方淋巴结清扫的再思考

直肠淋巴流向的研究从1895年D. Gerota的研究开始,提出了直肠淋巴流向可以分为上、中、下三个方向,经过很多学者的进一步研究修正,现普遍认为侧方淋巴流向可以分为4个方向：1.前方,由膀胱下动脉,前列腺动脉,经闭孔动脉到髂总动脉;2.沿直肠中动脉到髂内动脉;3.沿着骶中动脉和骶外侧动脉到腹主动脉分叉部位;4.沿着直肠下动脉到髂内动脉。侧方淋巴结转移主要发生在低位直肠癌,浸润深度大于肌层者,而转移的侧方淋巴结并不包括在直肠癌全直肠系膜切除术（TME）范围之内。NCCN直肠癌诊疗指南中没有提及侧方淋巴结的概念,日本大肠癌规约则认为有适应证的低位直肠癌应行侧方淋巴结清扫术。西方学者认为直肠癌侧方淋巴结转移是全身疾病,侧方淋巴结清扫难以改善总体临床结局;日本学者则认为是局部疾病,对低位直肠癌规范手术为TME＋侧方淋巴结清扫。西方学者认为术前放化疗可替代侧方淋巴结清扫;东方学者则认为对于术前放化疗不敏感的直肠癌患者,侧方淋巴结清扫术仍不失为一个可供选择的治疗方案。低位直肠癌患者是否应行预防性盆腔侧方淋巴结清扫仍存在争议,但治疗性侧方淋巴结清扫术则是日本的直肠癌规范治疗。不少研究报道了腹腔镜侧方淋巴结清扫术的初步探索结果,认为其是安全有效的,但其与开放手术的远期肿瘤学结果对比仍需多中心随机对照研究验证。     

侧方淋巴结清扫在国内低位直肠癌治疗中应用的Meta分析

目的:评价侧方淋巴结清扫在国内低位直肠癌治疗中应用价值.方法:运用M e t a分析的方法对我国2005-01/2015-09公开发表的有关侧方淋巴结清扫在低位直肠癌中应用的11篇文献资料进行综合分析.结果:侧方清扫组手术时间明显长于未清扫组,合并加权均数差(weighted mean d i ff e r e n c e,W M D)为47.79 m i n,且差异有统计学意义(P0.00001).侧方清扫组手术失血量高于未清扫组,合并加权均数差为27.84 m L,且差异有统计学意义(P0.0001).侧方淋巴结清扫组5年生存率高于未清扫组(59.8%vs 51.3%),差异具有统计学意义P0.05(P=0.02).侧方淋巴结清扫组三年生存率明显高于未清扫组(81.6%vs63.5%),差异具有统计学意义(P0.00001).侧方淋巴结清扫组的局部复发率明显低于未清扫组(8.4%vs 16.9%),差异具有统计学意义(P=0.0003).Ⅰ期及ⅡA期行侧方淋巴结清扫对于局部复发的影响差异无统计学意义(PⅠ期=0.96,PⅡA期=0.05).Ⅲ期低位直肠癌侧方淋巴结清扫组局部复发率明显低于未清扫组(14.5%vs 22.1%),P0.05(P=0.01)差异具有统计学意义.结论:我国低位直肠癌患者行侧方淋巴结清扫能有效的延长患者的5年生存率及3年生存率,降低局部复发率(尤其是Ⅲ期低位直肠癌),改善患者预后,但会增加手术时间及术中出血量.     

直肠癌侧方淋巴结清扫中国临床开展的现状

尽管目前东西方对于直肠癌侧方淋巴结清扫仍存争议,但中国学术界依据现有的循证医学证据制定了符合中国国情的侧方淋巴结清扫相关共识、指南和规范。相较于日本,国内侧方淋巴结清扫指征把握更加严格,仅当有明确影像学证据疑诊存在侧方淋巴结转移时,才会选择性进行清扫,常规清扫区域也仅限于髂内和闭孔周围。基于全面了解盆腔解剖结构的前提下,以筋膜为导向的两间隙清扫现已成为中国侧方淋巴结清扫的主流方案,该术式在明确清扫边界、保护神经功能、彻底清除侧方淋巴结等方面具有明显优势。未来随着更多的高质量侧方淋巴结清扫研究的进行,将会有更多的证据来规范直肠癌侧方淋巴结清扫的临床应用。     

体外离断直肠在NOSES Ⅰ式低位直肠癌根治术中的应用（附六例报告）

近年来,经自然腔道取标本手术（NOSES）已然在结直肠外科得到广泛的认可和运用,其在保证根治效果的同时,极大地减轻患者术后的痛苦。随着对NOSES理论体系认识的加深,NOSES Ⅰ式又得到了进一步更新完善和改良,而近年来达芬奇机器人应用于NOSES手术又能够克服传统腹腔镜的一些操作局限,本文为达芬奇机器人应用于改良NOSES Ⅰ式在低位直肠癌根治术的可行性及经验分享。     

达芬奇机器人手术系统在直肠癌侧方淋巴结清扫中的应用进展

达芬奇机器人手术系统具有三维高清图像和操作稳定灵活的优势,已广泛应用于直肠癌手术,并成为侧方淋巴结清扫的新方法。本文在介绍机器人手术系统特点的同时,结合本中心的经验对机器人侧方淋巴结清扫的应用现状进行回顾,并对其关键技术进行介绍。目前,机器人侧方淋巴结手术的安全性和有效性已得到肯定,与腹腔镜及开腹手术相比具有潜在优势。相信随着手术设备的进步和高质量临床研究的开展,机器人手术系统将在直肠癌侧方淋巴结清扫手术中发挥更重要的作用。     

Prognostic significance of lateral lymph node dissection in node positive low rectal carcinoma

Purpose  

This study was performed to identify patients who would benefit from lateral lymph node (LLN) dissection for advanced low rectal carcinoma.     

Laparoscopy-assisted lateral pelvic lymph node dissection for advanced rectal cancer

In Japan, there has been no indication of laparoscopic surgery for advanced lower rectal cancer because of the problem about the treatment of lateral pelvic lymph node metastasis. We report a new technique which allows lateral pelvic lymph node dissection like in open surgery for advanced rectal cancer. After laparoscopic total mesorectal excision for rectal cancer, a surgical incision of approximately 8 cm is placed in the supra-pubic area. Then, the latero-vesical area of the retroperitoneum, latero-vesical space is dissected bluntly with forceps. The external iliac artery and vein are taped and lymph node dissection is performed. As the external iliac vein is pulled internally, fatty tissue including lymph nodes in the obturator space is separated from the psoas major muscle. After completing of such a procedure, the obturator nerve is indentified in the fatty tissue with surrounding lymph nodes. As the external iliac vein is pulled laterally, fatty tissue including lymph nodes in the oburator space is dissected by fat aspiration procedure (FAP) using a suction tip. FAP is helpful to confirm the vascular system, by which the obturator space is skeletonized and anatomical structures are identified clearly.     

Prognostic value of lateral lymph node metastasis for advanced low rectal cancer

AIM： To evaluate the risk factors for lateral lymph node metastasis in patients with advanced low rectal cancer, in order to make the effective selection of patients who could benefit from lateral lymph node dissection, as well as the relationship of lateral lymph node metastasis with local recurrence and survival of patients with advanced low rectal cancer. METHODS： A total of 96 consecutive patients who underwent curative surgery with lateral pelvic lymphadenectomy for advanced lower rectal cancer were retrospectively analyzed. The relation of lateral lymph node metastasis with clinicopathologic characteristics, local recurrence and survival of patients was identified. RESULTS： Lateral lymph node metastasis was observed in 14.6% （14/96） of patients with advanced low rectal cancer. Lateral lymph node metastasis was detected in 10 （25.0%） of 40 patients with tumor diameter ≥ 5 cm and in 4 （7.1%） of 56 patients with tumor diameter 〈 5 cm. The difference between the significant （X^2 = 5.973, P = two groups was statistically 0.015）. Lateral lymph node metastasis was more frequent in patients with 4/4 diameter of tumor infiltration （7 of 10 cases, 70.0%）, compared with patients with 3/4, 2/4 and 1/4 diameter of tumor infiltration （3 of 25 cases, 12.0%; 3 of 45 cases, 6.7%; 1 of 16 cases, 6.3%） （X^2 = 27.944, P = 0.0001）. The lateral lymph node metastasis rate was 30.0% （9 of 30 cases）, 9.1% （4 of 44 cases） and 4.5% （1 of 22cases） for poorly, moderately and well-differentiated carcinoma, respectively. The difference between the three groups was statistically significant （X^2 = 8.569, P = 0.014）. Local recurrence was 18.8% （18 of 96 cases）, 64.3% （9 of 14 cases）, and 11.0% （9 of 82 cases） in patients with advanced low rectal cancer, in those with and without lateral lymph node metastasis, respectively. The difference between the two groups was statistically significant （X^2 = 22.308, P = 0.0001）. Kaplan-Meier survival analysis showed significant impr     

Lateral lymph node dissection for lower rectal cancer

BACKGROUND/AIMS: This study was conducted to evaluate the effects of lateral lymph node dissection (LLD) on overall survival, disease-free survival, and local recurrence for the patients with lower rectal cancer. METHODOLOGY: From 1990 through 2000, 169 consecutive patients with T2 (TNM classification) or more advanced, extended lower rectal cancer (located below the peritoneal reflection) underwent curative resection at Kanagawa Cancer Center were reviewed. One hundred and forty-three patients who underwent LLD and the 26 patients who did not were entered in this study. RESULTS: Cox's multivariate regression analysis showed T stage (TMN classification), N stage (TNM classification), and LLD were found to be significantly related to the rates of both cumulative survival and disease-free survival. That mean LLD was identified as a significant prognostic factor. But disease-free survival did not differ significantly between the patients who underwent LLD and those who did not undergo LLD in stage I, II, or III disease (p = 0.3681, p = 0.1815, and p = 0.0896, respectively). The local recurrence rate was similar in patients who received LLD (17.5 percent) and in those who did not receive LLD (23.1 percent; p = 0.498). But 7 patients with lateral lymph node metastasis (33.3 percent) remained disease free. And these patients had local lateral lymph node metastasis and benefited from LLD. CONCLUSIONS: LLD can substantially improve outcomes in selected patients at high risk for lateral lymph node metastasis. A randomized controlled clinical study is necessary to clarify the role of LLD in the treatment of rectal cancer.