不可切除结直肠癌肝转移的转化性治疗策略

手术是治疗结直肠癌肝转移最有效的也是惟一有可能治愈的手段,但是大多数结直肠癌肝转移病人并不能够行肝转移灶切除手术。近些年,用各种细胞毒药物和（或）靶向药物等使不可切除的肝转移病灶缩小,转化为可切除,继而行手术切除,从而获得治愈的可能。转化性治疗的目的是获得最佳反应率,而不是获得最大反应率。术前转化性化疗应选择高效化疗方案,并尽量缩短疗程。具体方案选择方面,KRAS野生型病人推荐西妥昔单抗联合FOLFOX/FOLFIRI,其中5-氟尿嘧啶持续给药,而KRAS突变型病人考虑贝伐珠单抗联合两药化疗或者三药化疗方案。在行转化性治疗时,一旦转移灶转化为可切除,应积极手术切除。     

结直肠癌肝转移的外科治疗进展

一、手术适应证及手术时机的选择结直肠癌单纯转移至肝脏者占结直肠癌患者的 2 5 %,局限于肝一叶者又占肝转移的 2 5 %,因此结直肠癌出现肝转移且为单个结节或局限于一个肝叶的不超过 5 %,这部分患者行根治性肝切除率极高 ,可达 95 %左右[1] 。目前手术指征包括 :(1)肝转移病灶为孤立结节或病变范围较局限 ;(2 )无肝外转移或邻近脏器 (膈肌、门静脉 )转移 ;(3)结直肠癌切除后肝转移 ,原发癌灶局部复发可切除者 ;(4 )肝转移癌灶手术切除后复发者 ,病灶较局限 ,且无肝外转移也可考虑再次手术切除 ;(5 )出现肺部转移可行手术治疗者。Ｖｏｇｔ等…     

通过转化治疗提高结直肠癌肝转移手术切除率的新进展

目的了解通过转化治疗提高结直肠癌肝转移手术切除率的外科治疗新进展,评估预后评估模型在肝内转移灶切除术后的应用价值,进一步指导患者术后的综合治疗,从而控制疾病快速进展,改善患者的生存质量。方法收集国内外有关结直肠癌肝转移外科治疗新进展的文献,就结直肠癌肝转移的手术切除指征、预后评估模型以及如何通过转化治疗提高其手术切除率的新进展进行综述。结果通过积极的转化治疗,能够使部分结直肠癌肝转移患者接受手术切除肝内转移灶。对于自始至终均无法接受手术切除肝内转移灶的患者,术前化疗、分子靶向治疗药物、多种介入治疗等转化治疗方案均不失为安全、有效的治疗方法,其对患者的生活质量的提高、生存时间的延长有一定的效果。结论我们应该加强对结直肠癌肝转移转化治疗的重视,积极推动预后评估模型在肝内转移灶切除术后的应用。     

��ֱ������ת��ת�����ƺ�����ʱ������ʽѡ��

肝脏是结直肠癌最常见的转移部位,手术切除是惟一可能治愈的方法,通过积极的转化治疗可以使一部分不可切除的肝转移病灶转化为可切除,并获得良好的生存。基于转化治疗后肝切除预后与转化治疗的线数、疗程等有关,多程化疗后带来的肝脏毒性及术后并发症增加等情况,建议在高强度、高效化疗适当疗程后,肿瘤退缩至符合可切除标准即可。关于最佳手术方式、同期肝转移原发灶与转移灶处理先后顺序问题,目前没有定论,建议由多学科综合治疗团队根据具体情况制定个体化的治疗方案。     

结直肠癌肝转移的转化治疗

对结直肠癌肝转移来说,手术是惟一的治愈手段。但80%的病人初始是不可切除的,将不可切除肝转移转化为可切除是提高结直肠癌总体存活率的关键。目前常用的转化手段有全身化疗（包括单纯化疗、化疗联合靶向药物等）、肝动脉灌注（HAI）、射频消融（RFA）、联合门静脉结扎或栓塞的分期肝切除、联合肝脏分隔及门静脉结扎的二步肝切除等。了解各种转化治疗的有效率和适应证是选择合适治疗的前提。     

���Ӱ���ҩ����ת���Խ�ֱ�����ۺ������еĺ���Ӧ�����о�����

根据病人状况和治疗目标设定治疗策略是目前结直肠癌重要治疗原则。对于潜在可切除的转移性结直肠癌,更高的肿瘤缓解率将不可切除病灶转化为可切除病灶的概率进一步提高,达到延长总生存期甚至治愈的目的,因此选择客观缓解率高的联合方案更适合;对于不可切除但肿瘤进展迅速同时合并明显临床症状的病人,缩小肿瘤、延长肿瘤控制时间、改善生活质量应作为主要治疗目标,因此具备近期疗效高的联合方案适于该类病人;对于肿瘤进展缓慢的不可切除的转移性结直肠癌,选择毒性反应相对较小的方案延缓肿瘤增长应作为合理的策略,单药对该类病人也具有一定价值。临床研究证实分子靶向药物联合化疗进一步提高了转移性结直肠癌的客观疗效以及生存期,但在转移性结直肠癌综合治疗中如何根据病人状况及肿瘤特点,通过多学科协作分析,筛选出分子靶向药物敏感的疗效预测因子、探讨分子靶向药物与细胞毒药物之间的相互作用、探寻其耐药机制,合理应用分子靶向药物,优化最佳治疗方案,并选择恰当的时机、是实现治疗目标、改变病人疾病转归的重要保证。     

晚期结直肠癌的外科治疗进展

尽管结直肠癌的综合治疗有了很大的进展,但局部晚期(T3期和T4期)以及转移性结直肠癌的治疗仍然是具有挑战性的课题.新辅助放化疗、靶向治疗等研究取得了许多令人鼓舞的结果,但从外科处理的角度,仍然有诸多争议存在.包括对局部晚期结直肠癌多脏器切除的扩大根治指征、对结直肠癌肝转移和肺转移的最优化处理策略等.R0切除是转移病灶的首选处理策略,但仅适用于部分患者.利用化疗联合靶向药物的转化治疗策略将部分不可切除的转移肿瘤转化为可切除,也为进一步的外科治疗创造了机会.本文从局部晚期结直肠癌、结直肠癌肝和肺转移的外科治疗为切入点,简要阐述晚期结直肠癌的治疗进展.     

伴有同时性不可切除肝转移的结直肠癌患者治疗的思考

对于肝转移灶不可切除的结直肠癌患者,需要经过多学科刚队讨论,采用全身化疗、介入化疗和肝转移灶消融毁损术等多种方法改善患者预后．应结合患各和肿瘤的特征将患者分为不同组刖,制定各自的治疗同标和治疗策略。其中部分患者,如果化疗后可能转化为潜在可切除,建议给予强化的三药联合方案,尽髓缩短疗程,从而获得肿瘤的最佳反应率．继而行手术切除。KRAS野乍型的患并推荐西妥子单抗联合FOLFOX或FOLFIRI方案,而且旦转移灶转化为可切除,就应该积极手术切除。埘十肝转移灶不可切除且原发灶尤症状的患者,手术切除原发灶似乎可以获得生存收益。关于非手术治疗的选择,目前临床上还存在争议。     

Ⅳ期结直肠癌转移病灶的局部根治性与姑息性处理进展

正手术完全切除肝/肺转移灶仍是目前治愈结直肠癌肝/J|肺转移的最佳方法,推荐符合手术适应证的患者在适当的时机接受手术治疗初始不可切除的患者推荐经多学科团队讨论后,行全身和(或)局部治疗,以期转化为可切除并择期接受手术此外,射频消融(RFA)、立体定向放疗(SBRT)等局部治疗也逐渐被认为可达到根治转移灶的效果现分别探讨结直肠癌肝转移、肺转移、腹膜转移和盆腔转移中局部治疗的进展。     

肝移植治疗不可切除性直肠癌肝转移1例

本例不可切除性直肠癌肝转移患者确诊直肠癌时已合并肝内不可切除多发转移, 切除原发病灶后采用FOLFOX方案化疗+贝伐珠单抗靶向治疗。2年后患者肝内转移灶增多增大, 未见肝外转移灶及原位复发, 实施肝移植手术, 术后采用他克莫司+西罗莫司免疫抑制方案, 雷替曲塞化疗。肝移植3年后, 本例患者肿瘤复发, 总生存期为6年。本例提示, 对于不可切除性结直肠癌肝转移患者, 在未发现原位复发及其他远隔转移的情况下实施肝移植手术可以提高患者的生活质量并获得较好的预后。     

结直肠癌肝转移的新辅助治疗

随着人们生活水平的提高以及饮食结构的改变,结直肠癌发病率呈逐年上升的趋势.约有25%的结直肠癌患者发现时即伴有肝转移.原发肿瘤联合肝转移灶一起切除能够提高患者的生存期,因此如何能够提高结直肠癌肝转移患者的手术切除率成为治疗的关键.新辅助治疗的提出为结直肠癌肝转移患者的治疗提供了新的契机.     

�����г���ֱ������ת�Ʋ���ԭ����Ĵ���

结直肠癌肝转移发生率高,且临床就诊者大多数肝转移灶为不可切除。尽管关于不可切除结直肠癌肝转移病人原发灶的处理尚有一定争议,但随着结直肠癌原发灶处理经验的积累,多学科综合治疗团队(MDT)模式的开展,转化性治疗思维的应用,"个体化治疗"原则的实施,针对不可切除结直肠癌肝转移病人原发灶的处理逐步形成包括手术切除原发灶在内较合理的综合治疗体系。手术切除、新辅助治疗与姑息治疗的合理选择是改善不可切除结直肠癌肝转移病人生存质量及提高生存期,获得最佳治疗效果的关键。     

不同阶段结直肠癌肝转移的手术策略

结直肠癌患者容易发生肝转移,手术是目前治疗结直肠癌肝转移的最佳手段。但肝转移的发生时机不同,所采取的手术策略也不同。结直肠癌确诊时发生肝转移的患者,其手术时机一直存在争议;结直肠癌根治术后发生肝转移的患者只要具有手术指征,均应再次实施手术治疗;部分暂不能手术的结直肠癌肝转移患者,多采用化疗、RFA、介入等辅助治疗可使患者重新获得手术机会,但在临床应用中也存在不少困惑。因此,针对不同阶段的结直肠癌肝转移,应采用多学科综合治疗,制订个体化的治疗方案才是改善患者预后的关键。     

Was leisten Darmkrebszentren bei der Diagnostik und Therapie kolorektaler Lebermetastasen?

Successful resection of liver metastases increases overall survival and can even be a curative approach in patients with colorectal cancer (CRC) and isolated liver metastases. Resection of liver metastases has clearly changed the therapy of this group of patients and has become a standard procedure that is being used increasingly more. Accordingly, liver metastasis resection has been included in the German evidence-based guidelines and also in international guidelines on the treatment of CRC. The treatment of colorectal liver metastases requires a multidisciplinary team of experts in the disease, including experienced radiologists, medical oncologists, radiotherapists, pathologists and surgeons. The interdisciplinary approach to the treatment in specialized tumor boards staffed by qualified experts is a prerequisite for successful certification as a colorectal cancer center by the German Cancer Society. Regular audits ensure that these requirements and that defined quality indicators regarding the tumor board and primary and secondary liver metastasis resection, are fulfilled. The certification system of the colorectal cancer centers requires and promotes conditions that allow an optimal and guideline-oriented treatment of colorectal liver metastases both at the level of personnel and infrastructure of a given center. The high primary and secondary resection rates in these centers testify that the multidisciplinary teams are effective. A detailed analysis of the audit reports reveals the close collaboration of all partners within the certified networks. These networks also comprise external cooperation with highly specialized hospitals if and when necessary. However, the annual report of the certificated colorectal cancer centers also demonstrates areas for further improvements in multidisciplinary cooperation.     

Tumoricidal effects and patient survival after hyperthermic liver perfusion

Hyperthermic liver perfusion for four hours at 42.0 degrees C to 42.5 degrees C was used as the sole modality of therapy for cancer confined to the liver in eight patients. Two patients had melanoma, one had cholangiolar carcinoma of the liver, and five had liver metastases from colorectal carcinoma. Two postoperative deaths occurred, both in patients with colorectal carcinoma metastases. Response was indicated by computed tomographic and/or liver biopsy or autopsy findings of tumor necrosis. There were five responders to hyperthermic liver perfusion among the six survivors. Hyperthermic liver perfusion was an effective tumoricidal agent for hepatic metastases from colorectal cancer; ie, tumor necrosis occurred in all five patients, as well as in the two who died, as shown by autopsy findings. Conversion to a disease-free state with hyperthermic perfusion may be possible with other treatment modalities used in combination or sequence.     

Additive Chemotherapie bei Lebermalignomen zur Verbesserung der Operabilität

Complete tumor resection is the only curative option for patients with colorectal liver metastases. Hepatic resection is frequently not possible for technical reasons: because of large tumors, multiple or bilateral metastases, or tumors that are too close to vessels. In these cases chemotherapy might downstage the tumor volume and facilitate secondary curative resection in patients initially not eligible for curative surgery. Treatment with fluorouracil (5-Fu) alone has resulted in disappointing response rates of about 10-20% in patients with colorectal liver metastases, which make these protocols useless in the neoadjuvant setting. Because regional chemotherapy into the hepatic arteria results in significantly higher response rates (40-50%), some studies have documented some success in secondary curative surgery after regional chemotherapy of initially unresectable colorectal liver metastases. However, regional chemotherapy is invasive and therefore not standard therapy for every patient with colorectal liver metastases. Recently new exciting treatment options have become available for colorectal cancer. Combinations of chemotherapy consisting of irinotecan and 5-Fu/FA or oxaliplatin and 5-Fu/FA result in response rates of 50% and can be considered a new standard first-line chemotherapy for patients with metastatic colorectal cancer. Recently, two encouraging retrospective studies have been published with chronomodulated chemotherapy of oxaliplatin and 5-Fu/FA in the setting of neoadjuvant chemotherapy for patients with unresectable colorectal liver metastases. With this multidisciplinary approach, antitumor activity of chemotherapy appears to be translated into a long-term survival benefit and some patients with initially unresectable colorectal liver metastases can potentially be cured. As a consequence, on the premises of close cooperation between surgeons and internists, more patients with metastatic colorectal cancer will be cured in the future.     

多学科团队模式下结直肠癌肝转移的转化性治疗（附86例报告）

目的 探索适用于初始不可切除的结直肠癌肝转移（colorectal liver metastases,CLMs）病人转化性治疗的多学科团队（MDT）模式,评价转化性治疗的安全性和有效性。方法 回顾性分析2008年1月至2011年12月复旦大学附属中山医院经过MDT诊治模式并转化性治疗成功的86例CLMs病人的临床资料,评价MDT诊治模式下转化性治疗的实施及近远期疗效,并分析预测病人预后的因素。结果 86例病人随访41.0（24～68）个月,转移灶复发73例,39例死亡。病人的1、2、3年累积总存活率（OS）分别为90.6%、75.6%、65.1%;中位生存时间为（47.5±3.1）个月。1、2、3年无疾病存活率（DFS）分别为72.1%、48.8%、31.4%,中位DFS时间（22.0±2.9）个月,与99例初始可切除性CLMs的OS和DFS相比差异无统计学意义（P >0.05）。86例病人围手术期病死率1.5%,手术并发症发生率24.4%且经过积极支持治疗后均痊愈。肿瘤缓解程度与早期肿瘤退缩对转化性治疗病人的预后有预测作用。结论 对于不可切除的CLMs,MDT指导下的转化性治疗安全、有效,转化治疗成功病人的中期生存效果与初始可切除性CLMs相似,长期生存效果值得期待。     

Efficacy of direct electrical current therapy and laser-induced interstitial thermotherapy in local treatment of hepatic colorectal metastases: an experimental model in the rat

BACKGROUND: Local antitumoral therapy of metastases is an important tool in the palliative treatment of advanced colorectal cancer. Several authors have recently reported on successful local treatment of different malignant diseases with low-level direct current therapy. The aim of the present study was to compare the effectiveness of direct current therapy with the established laser-induced thermotherapy (LITT) on experimental colorectal liver metastases. MATERIALS AND METHODS: Colorectal metastases were induced in 49 BD IX rats by injection of colon cancer cells beneath the liver capsule. Three weeks after induction, tumor volumes and sizes were estimated with magnetic resonance imaging and by manual measurement of the largest tumor diameter, and two treatment groups and two control groups were established. Direct current (80 C/cm(3)) versus LITT (2 W; 5 to 10 min) was locally applied via laparotomy. Control groups were sham treated. Tumor growth was analyzed 5 wk after therapy by manual measurement of the maximal diameter and histopathological examination was performed. RESULTS: Measurement of tumor sizes 5 wk after therapy confirmed a significant antitumoral effect of direct current (1.6-fold tumor enlargement) and of LITT (1.3-fold tumor enlargement), compared with controls (2.8-fold and 2.9-fold tumor enlargement). However, after 5 wk, LITT was significantly more effective in limiting tumor growth than direct current treatment (P 相似文献