联合肝脏离断和门静脉结扎二步肝切除术治疗结直肠癌肝转移的研究现状

目前,结直肠癌肝转移的最佳治疗策略仍是根治性手术切除,而对于巨大肿瘤或者多发肿瘤患者,常常面临肝切除术后残余肝脏体积不足的问题,容易出现术后肝衰竭等严重并发症。联合肝脏离断和门静脉结扎二步肝切除术(ALPPS)是一种新颖的二步肝切除术,可使残余肝在一期术后快速增生,增加肝脏肿瘤的可切除性,降低术后肝衰竭的风险。虽然ALPPS可实现肿瘤R0切除,延长患者生存期。但因其较高的术后并发症率和病死率饱受争议,结合国内外相关研究,对ALPPS在结直肠癌肝转移中的应用现状及临床价值进行阐述。     

结直肠癌肝转移影像诊断策略

超声、CT、MRI、PET/CT及PET/MR在结直肠癌肝转移诊治中广泛应用,NCCN指南提出结直肠癌肝转移影像学诊断首选增强MR,但对于每个结直肠癌肝转移患者如何选择合适的影像学检查,充分合理地应用有限的资源是临床关注的重点。结合国内外文献及笔者多年的MDT经验,对于结直肠癌肝转移患者,在参照指南的基础上更要结合患者自身病情,由多学科专家讨论做出合理的影像诊断。     

脂肪性肝病与结直肠癌肝转移的关系

目的 研究脂肪性肝病对结直肠癌肝转移的影响.方法 回顾性研究1993年1月至2002年12月共890例临床资料完整的结直肠癌患者,其中127例伴脂肪肝.763例无脂肪肝.分别统计两组患者的一般情况、病理资料、肝转移及术后近期死亡情况等临床资料,同时随访患者术后生存期、术后异时性肝转移并进行统计分析.结果 脂肪肝组肝转移7例,明显少于非脂肪肝组(102例,P=0.012).脂肪肝组肿瘤平均直径[(4.15±1.80)cm]小于非脂肪肝组[(4.77±2.25)cm,P=0.0016].脂肪肝组主要为Dukes A期(41/121,33.9%)和B期(40/121,33.1%)患者,而非脂肪肝组以Dukes B期(247/732,33.7%)和C期(232/732,31.75%)患者为主,差异有统计学意义(P＜O.05).两组获得随访资料的患者术后7年内远期生存率比较差异无统计学意义(P=0.3024).结论 脂肪性肝病患者结直肠癌肝转移率低,脂肪性肝病可能通过某种机制抑制肝脏转移性肿瘤的生长.     

腹腔镜与开腹肝切除术治疗结直肠癌肝转移效果和安全性比较的Meta分析

目的系统评价腹腔镜肝切除(LLR)与开腹肝切除(OLR)治疗结直肠癌肝转移(CRLM)的临床效果和安全性。方法计算机检索中文(知网、万方、维普)和英文数据库(PubMed、Cochrane library、Embase)关于LLR与OLR治疗CRLM的临床对照研究,检索时间为数据库建立至2019年6月。中文检索词包括:结直肠癌肝转移、腹腔镜肝切除术、开腹肝切除术;英文检索词包括:colorectal cancer,colorectal liver metastases,laparoscopic hepatectomy,laparoscopic liver resection,open hepatectomy,open liver resection。对纳入的研究进行质量评价和数据提取后,采用RevMan5. 3软件进行Meta分析。结果纳入23项研究,共计4204例患者,其中LLR组1558例,OLR组2646例。Meta分析结果显示,与OLR组比较,LLR组术中出血量减少[均数差(MD)=-145. 48,95%可信区间(95%CI):-190. 96～-100. 00,P 0. 001]、输血率降低[比值比(OR)=0. 41,95%CI:0. 29～0. 60,P 0. 001]、术后并发症发生率降低(OR=0. 55,95%CI:0. 47～0. 65,P 0. 001)、术后住院时间缩短(MD=-2. 69,95%CI:-3. 29～-2. 10,P 0. 001)。两组在手术时间、围手术期病死率、R0切除率、1年和5年总体生存率及无瘤生存率等方面差异均无统计学意义(P值均 0. 05)。结论 LLR治疗CRLM是安全可行的,且近期疗效优于OLR,但该结论仍需更多临床随机对照试验来予以验证。     

介入治疗在结直肠癌肝转移中的作用

结直肠癌(colorectal cancer,CRC)是我国常见的恶性肿瘤,发病率逐年增高,已跃居第3~5位,在大城市增幅更快[1]。肝脏是CRC的常见转移部位,国外报道约30%的患者伴有同时性CRC肝转移(colorectal liver metastases,CRLM)[2],5年累积异时性CRLM发生率也有14.5%左右,约有76.8%的患者仅发生肝内转移而无其他肝外转移[3],CRLM是     

同时性结直肠癌肝转移患者的生存分析

目的分析结直肠癌合并同时性肝转移患者的生存状况和相关影响因素。 方法回顾性分析2000年至2010年复旦大学附属中山医院收治的1061例结直肠癌合并同时性肝转移患者的病例。收集所有患者的临床资料、病理特征、治疗策略、住院费用、随访状况等,进行生存状况分析,并采用单因素和Cox比例风险回归模型等分析影响结直肠癌肝转移生存的相关因素。 结果肝转移灶可切除患者中,同期切除肠道原发灶和肝转移灶与分期切除患者的住院费用分别为25693元、34129元(P<0.05),手术并发症(分别为24.5%、20.5%)和总生存期方面(分别为48.5月、47.0月)无显著差异。肝转移灶不可切除且原发灶无症状的患者中,原发灶切除的患者总体中位生存时间明显好于原发灶未切除的患者(分别为19.0月、9.3月,P<0.001)。肠道原发灶分化Ⅲ～Ⅳ级、肝转移灶≥4个、最大肝转移灶直径≥5 cm、肝外转移、肠道原发灶未手术切除和肝转移灶非手术治疗是影响肠癌同时性肝转移患者预后的独立危险因素。将上述6个危险因素各设定为1分,所有患者分为低风险组(0～1分)、中风险组(2～3分)和高风险组(4～6分),5年存活率分别为51%、16%和0%(P<0.001)。 结论结直肠癌合并同时性肝转移患者中,原发灶和转移灶均可切除的可予以同期切除,原发灶可切除且无出血梗阻症状的不可切除的肝转移仍建议在合适时机切除肠道原发灶。根据上述6个独立预后因素所建立的预测模型可以指导临床采取合适的治疗方案。     

结直肠癌肝转移的可切除性判断

结直肠癌最好发的转移部位是肝脏,手术是治愈结直肠癌肝转移并获得长期生存的唯一可能方式。就目前多学科治疗背景下,高效能的化疗方案联合靶向药物以及多种手术方式,如传统二步肝切除联合门静脉栓塞术/门静脉结扎术（portal vein embolization,PVE/portal vein ligation,PVL）及联合肝脏劈离及门静脉结扎的二期肝切除（associating liver partition and portal vein ligation for staged hepatectomy,ALPPS）的出现,包括各种消融等局部治疗手段拓展了过去对于肝脏可切除性的定义,而依据新的可切除标准对于可切除性的判断仍存在较大差异,本文将就肝脏可切除性判断展开探讨。     

结直肠癌肺转移的外科治疗

结直肠癌是我国的常见恶性肿瘤,发病率居第三位。约20%的结直肠癌初诊时就伴有远处转移,其中肺是最常见的转移部位之一。大量文献表明,对于结直肠癌伴有局限性肺转移的患者手术切除转移病灶,术后的5年生存率为21%～64%。存在其他可切除转移灶并不是手术禁忌。对于手术耐受良好的肺部转移瘤术后复发的患者,再次手术仍可生存获益。距离病灶0.5cm～1.0cm楔形切除是肺外周型病灶的经典术式。对于结直肠癌肺转移瘤手术胸腔淋巴结清扫仍有不同观点。目前公认的结直肠癌肺转移预后不良的因素包括：多发肺转移瘤、癌胚抗原水平升高、胸内淋巴结转移、无瘤间期较短。基于精准医学的个体化治疗将是未来进一步改善预后的关键。     

不可切除的结直肠癌肝转移灶局部治疗进展

肝脏是结直肠癌发生转移最主要的靶器官,手术切除是治疗肝转移最理想的方式,但对于不可切除的肝转移,局部控制是治疗的首要目标,在全身化疗的基础上,局部治疗发挥了重要的强化和补充作用。目前常用的局部治疗方式包括消融治疗、肝脏导向化疗、放射治疗等。近年来这些方式在低毒副作用、高可重复性、长期控制等方向均有一定的进展。     

结直肠癌肝转移相关microRNA的研究现状

肿瘤的转移是一个多步骤复杂的过程,肝转移是结直肠癌最常见的转移方式之一,对转移机制的理解和深入研究有助于寻求解决结直肠癌肝转移的方法,当前研究认为microRNA参与了肿瘤的转移与复发,通过对结直肠癌肝转移相关microRNA的研究,为疾病的发生发展、诊断治疗及预后等方面的研究提供了新的思路。归纳了结直肠癌肝转移相关microRNA的研究进展,回顾了microRNA的生物学功能以及分子机制,表明microRNA在肿瘤转移领域具有重要的意义,尤其在结直肠癌肝转移方面发挥着重要的作用。     

Comparison of surgical outcomes in patients with colorectal liver metastases versus non‐colorectal liver metastases: A Chinese experience

Aim: To compare the surgical treatment outcomes between patients with colorectal liver metastases (CLM) and non‐colorectal liver metastases (NCLM). Methods: The study population consisted of 132 patients undergoing hepatectomy at Tianjin Medical University Cancer Hospital between January 1996 and December 2008. Survival analyses were used to assess the differences in prognosis and survival between groups. Results: The primary tumor site was colorectal in 60 (45.5%), breast in 16 (12.1%), lung in 14 (10.6%), non‐colorectal gastrointestinal in 12 (9.1%), genitourinary in 10 (7.6%), pancreatobiliary tumor (n = 8, 6.1%) and others in 12 (9.1%). A curative liver resection was performed in all patients by pathological findings. After a median follow‐up of 32 months, the overall 3‐ and 5‐year survival rate was 44.7 and 29.5% in all patients, respectively. The 3‐ and 5‐year survival rates were 53.3 and 36.7% for liver metastases from colorectal tumors, 62.5 and 43.8% from breast, 60.0 and 40.0% from genitourinary neoplasm, 41.7 and 25.0% from non‐colorectal gastrointestinal cancer, 28.5 and 15.0% from lung, 12.5 and 0% from pancreatobiliary malignancies, and 41.7 and 8.3% from other sites, respectively. Conclusions: Hepatic resection is an effective and safe treatment for liver metastases mainly depending on primary tumor sites. Hepatic metastases from non‐colorectal gastrointestinal cancer, pulmonary and pancreatobiliary malignancies have the worst prognosis; those from breast and genitourinary neoplasm show the best prognosis.     

Searching for the link; mechanisms underlying liver regeneration and recurrence of colorectal liver metastasis post partial hepatectomy

Despite excellent treatment of primary colorectal cancer, the majority of deaths occur as a result of metastasis to the liver. Recent population studies have estimated that one quarter of patients with colorectal cancer will incur synchronous or metachronous colorectal liver metastasis. However, only one quarter of these patients will be eligible for potentially curative resection. Tumor recurrence occurs in reportedly 60% of patients undergoing hepatic resection, and the majority of intrahepatic recurrence occurs within the first 6 months of surgery. The livers innate ability to restore its homeostatic size, and volume facilitates major hepatic resection that currently offers the only chance of cure to patients with extensive hepatic metastases. Experimental and clinical evidence supports the notion that following partial hepatectomy, liver regeneration (LR) paradoxically drives tumor progression and increases the risk of recurrence. It is becoming increasingly clear that the processes that drive liver organogenesis, regeneration, and tumor progression are inextricably linked. This presents a major hurdle in the management of colorectal liver metastasis and other hepatic malignancies because therapies that reduce the risk of recurrence without hampering LR are sought. The processes and pathways underlying these phenomena are multiple, complex, and cross‐communicate. In this review, we will summarize the common mechanisms contributing to both LR and tumor recurrence.     

结直肠癌肝转移腹腔镜/机器人同期联合切除技术指南(2017修订)

肝脏是结直肠癌患者常见的远处转移器官,在临床诊断结直肠癌时,已有15%~25%合并同时性肝转移^（[1-2]）。近年来其诊治理念不断更新,外科技术发展迅速,患者的生存效果显著改善,同时在很大程度上也得益于诊治规范化程度的提高,诊治指南对于规范其临床实践过程发挥着重要作用。目前的专家共识是,外科手术是此类患者可能获得长期生存的确定性手段;但在具体手术方式决策上,则存在着分期手术、     

Practical questions in liver metastases of colorectal cancer: general principles of treatment

Liver metastases of colorectal cancer are currently treated by multidisciplinary teams using strategies that combine chemotherapy, surgery and ablative techniques. Many patients classically considered non-resectable can now be rescued by neoadjuvant chemotherapy followed by liver resection, with similar results to those obtained in initial resections. While many of those patients will recur, repeat resection is a feasible and safe approach if the recurrence is confined to the liver. Several factors that until recently were considered contraindications are now recognized only as adverse prognostic factors and no longer as contraindications for surgery. The current evaluation process to select patients for surgery is no longer focused on what is to be removed but rather on what will remain. The single most important objective is to achieve a complete (R0) resection within the limits of safety in terms of quantity and quality of the remaining liver. An increasing number of patients with synchronous liver metastases are treated by simultaneous resection of the primary and the liver metastatic tumours. Multilobar disease can also be approached by staged procedures that combine neoadjuvant chemotherapy, limited resections in one lobe, embolization or ligation of the contralateral portal vein and a major resection in a second procedure. Extrahepatic disease is no longer a contraindication for surgery provided that an R0 resection can be achieved. A reverse surgical staged approach (liver metastases first, primary second) is another strategy that has appeared recently. Provided that a careful selection is made, elderly patients can also benefit from surgical treatment of liver metastases.     

Laparoscopic major hepatectomy can be safely performed with colorectal surgery for synchronous colorectal liver metastasis

Background

The optimal strategy for resectable synchronous colorectal liver metastases remains controversial. Although some authors advocate a staged treatment, an increasing number of studies have reported that combined colorectal and liver resection is safe. Laparoscopic combined resection in primary colorectal cancer with synchronous liver metastases has been reported but there are no specific data for major liver resections. In the present study, we evaluated the feasibility of a simultaneous entirely laparoscopic procedure, in the light of the benefits of laparoscopy in both colon and liver surgery, and discussed the benefits of this strategy.

Methods

Two cases are presented of totally laparoscopic major liver resections associated with laparoscopic colorectal resections for synchronous liver metastases with the emphasis on the technical aspects. Duration of surgery, blood loss and post-operative outcome were evaluated.

Results

Laparoscopic right hepatectomy or left hepatectomy with simultaneous colon resection for liver metastasis was feasible and safe with only one suprapubic 5-mm trocar added to the usual trocar sites. The mean duration of surgery was 327 min with a mean estimated blood loss of 200 ml. The post-operative course was uneventful.

Discussion

In selected patients, laparoscopic major hepatectomies for unilobular synchronous metastases can be safely performed simultaneously with colorectal surgery.     

经肝动脉化疗栓塞术治疗结直肠癌肝转移的研究进展

肝脏是公认的结直肠癌最普遍的转移器官,根治性切除术被认为是唯一可能治愈结直肠癌肝转移的治疗方案。但仅有约20%的患者能够接受手术治疗。对于已丧失手术机会的患者,经肝动脉化疗栓塞术(TACE)是被国内外学者广泛采用的首选治疗方案之一。介绍了现阶段临床上TACE治疗结直肠癌肝转移的应用基础、适应证、禁忌证、疗效、化疗药物及栓塞剂等。认为TACE是一种疗效肯定、微创、副反应少的姑息性治疗方案,可以作为不可切除结直肠癌肝转移患者的首选治疗方案。     

Fascin、CD_（24）、CD_（73）、Hsp27与大肠癌亲器官转移的相关性探讨

目的观察CD24、CD73、Hsp27和Fascin蛋白在大肠癌组织中的表达,探讨其与大肠癌亲器官转移的相关性及临床病理意义。方法应用免疫组织化学技术检测Fascin、CD24、CD73和Hsp27蛋白在20例无转移大肠癌和19例同时伴有淋巴结和肝脏转移的大肠癌的不同部位癌组织中的表达。结果转移性大肠癌原发灶与未转移大肠癌比较,CD73、Fascin的表达差异显著（P=0.009,0.009）,Hsp27、CD24的表达无明显差异。CD24在淋巴结转移灶的表达与肝转移灶和原发灶比较,差异显著（P=0.000,0.001）;原发灶和肝转移灶的表达比较,差异不显著。CD73肝转移灶的表达与淋巴结转移灶和原发灶比较差异显著（P=0.003,0.000）;而淋巴结转移灶和原发灶的表达比较无明显差异。Hsp27在肝转移灶的表达与原发灶比较,无明显差异;与淋巴结转移灶比较,差异显著（P=0.001）;在原发灶与淋巴结转移灶的表达比较差异显著（P=0.021）。Fascin在原发灶的表达与肝转移灶、淋巴结转移灶比较无明显差异。结论 CD24与大肠癌淋巴结转移相关,可能是大肠癌淋巴结转移的预测因子之一;CD73、Hsp27的高表达与大肠癌肝转移有关,Fascin的表达与大肠癌转移有关,但与大肠癌转移至淋巴结或肝脏无相关性。     

结直肠癌肝转移预后因素分析及治疗方式对生存期的影响

目的研究在原发癌切除术后,结直肠癌肝转移患者的临床特征与预后之间的相关性。方法对118例结直肠癌肝转移患者13个临床病理特征进行单因素生存分析及多因素COX风险回归模型的分析。各种治疗方法对1、3、5 a生存率及中位生存期的影响应用生存寿命表法进行比较。结果手术组的生存期明显长于姑息治疗组和未治疗组。原发癌的TNM分期、术前CEA、肝转移灶的最大径和发现时间、肝外转移的存在以及原发癌切除术后的治疗方式等6个因素对结直肠癌肝转移患者的中位生存期存在显著性影响（P〈0.05）。原发癌的TNM分期、术前CEA、肝转移灶的大小与结直肠癌肝转移长期生存的危险性呈正相关。结论结直肠癌肝转移患者的临床病理特征与患者预后有着密切关系。手术治疗,特别是手术联合全身化疗、肝动脉介入化疗等综合治疗比单纯治疗具有更佳的疗效。