同时性结直肠癌肝转移治疗策略

同时性结直肠癌肝转移(colorectal cancer with synchronous liver metastases,SCRLM)的治疗方法较多,其治疗要区分可切除和不可切除,很多治疗观点仍有争论,方法不能统一而论。作者通过分析比较国内外的相关报道,综合阐述,以促治疗达成规范,治疗效果能有所提高,为临床提供参考价值。     

结直肠癌可切除肝转移灶的术前化疗文献复习

结直肠癌是常见的肿瘤之一,近一半的患者最终会发生肝转移,肝转移灶切除是唯一的治愈方法。对于评估为可切除的肝转移灶,由于其术后复发率高,患者生存时间并未有显著延长,术前影像学难以发现的肝内微小转移灶成为局部复发的重要因素之一。术前化疗可以减少微小转移灶,增加R0切除（完整切除）率,减少术后复发风险。但是,是否所有术前评估为可切除肝转移灶的结直肠癌患者均可以从术前化疗中获益仍存在争议。     

同时性结直肠癌肝转移危险因素分析

目的：探讨影响结直肠癌肝转移的临床病理相关因素。方法：收集2010年至2014年南京大学鼓楼医院普外科结直肠癌患者201例的临床病理资料,分析同时性结直肠癌肝转移与临床病理因素的关系。采用非条件Logistic回归单因素分析,对有统计学意义的变量进行非条件Logistic回归多因素分析。结果：201例结直肠癌患者中,肝转移45例。单因素分析显示,肿瘤最大径、CEA、CA199、CA125、肿瘤T分期、分化程度、病理组织类型、糖尿病、肿瘤位置、吸烟是影响结直肠癌肝转移的危险因素。Logistic多因素分析,结果显示肿瘤最大径、CEA、CA199、CA125、肿瘤分化程度、病理类型、糖尿病是肝转移的独立危险因素。结论：肿瘤最大径、CEA、CA199、CA125、肿瘤分化程度、病理类型、糖尿病是同时性结直肠癌肝转移的独立危险因素。     

结直肠癌同时性肝转移同期切除切口与近期预后探讨

目的：结直肠癌同时性肝转移（synchronous colorectal liver metastases ,sCRLM ）同期切除时,切口是外科医生需要考虑的技术问题。本研究旨在探讨切口对同期切除近期预后的影响。方法：回顾性分析2009年1 月至2014年12月北京大学肿瘤医院肝胆胰外Ⅱ科37例同期切除的sCRLM 患者的临床数据。结果：Mercedes 切口（Mer）组19例,正中切口（Mid）组18例。2 组间患者一般情况、大体积肝切除比例、手术时间、术中出血量、术中第一肝门阻断时间无显著性差异。正中切口组中直肠患者更多（P < 0.001）。 2 组共发生并发症11例（32.4%）,其中Mer组9 例（47.4%）,Mid组3 例（16.7%）,两组比较无显著性差异（P = 0.08）。 术后住院时间 Mer组（22.1 ± 9.5）d,Mid组（17.2 ± 6.7）d,两组比较无显著性差异（P = 0.08）。当患者 BMI（bodymassindex）< 25时,并发症Mer组5 例（38.5%）,Mid组0 例（0%）,两组比较有显著性差异（P = 0.046）。 术后住院时间Mer 组（22.1 ± 10.5）d,Mid组（15.7 ± 5.3）d,P = 0.051。结论：sCRLM 患者进行同期切除时,正中切口可以满足术野暴露要求,相比Mercedes 切口,对直肠术野的暴露更有优势;当BMI<25时,正中切口可能会有更好的近期预后。     

结直肠癌同时性肝转移的预后因素分析

目的 探究结直肠癌同时性肝转移患者的临床病理特点,并分析影响其预后的相关因素,以期指导外科治疗决策.方法 回顾性分析中山大学附属第一医院自1994年8月至2009年12月收治的结直肠癌同时性肝转移患者231例,分析其预后与临床病理凶素的关系.结果 确诊时合并肝转移患者占同期结直肠癌患者总数的8.46%(231/2732).该组患者1、3、5年生存率分别为70.2%、21.9%,和11.4%,中位生存时间19个月.单因素分析显示:肿瘤周径(P=0.017)、浆膜侵犯(P=0.000)、肝转移分期(P=0.000)、浸润深度(P=0.010)、肿瘤分化程度(P=0.007)、手术方式(P=0.000)和化疗(P=0.041)影响患者预后.肝转移H1组患者1、3和5年生存率分别为88.4%、39.7%和21.3%,肝转移H2组分别为64.1%、15.7%和7.8%,肝转移H3组分别为55.0%、9.2%和0.0%(P<0.01).根治性手术组患者1、3和5年生存率分别为84.6%、37.9%和19.8%.姑息手术组分别为60.2%、24.0%和0.05%,减状手术或者未手术组1、3、5年生存率分别为37.0%、0.09%和0.0%(P<0.01).Cox回归模型多因素分析显示,只有肝转移分期(P=0.000)和手术方式(P=0.010)是结直肠癌肝转移患者的独立预后因素.结论 结直肠癌肝转移分期影响预后.应早期发现和诊治.对于结直肠癌仅有肝转移的患者应尽可能手术切除原发灶和肝转移病灶.化疗可以改善姑息术后患者的预后.     

结直肠癌肝转移外科治疗策略

目前手术切除是结直肠癌肝转移（CRLM）唯一具有治愈可能的治疗方式。近年来随着全身化疗及靶向药物的发展、肝动脉灌注化疗的应用,对于CRLM 治疗的有效率明显升高,通过手术获益的患者逐渐增多;而如射频消融、二步切除等外科技术的进步,也为更多CRLM 患者提供了治愈的机会。多学科诊疗模式（MDT ）也为更多CRLM 患者的个体化诊治创造了机会,使未来CRLM 的治疗向更加精准的方向发展。     

结直肠癌肝转移的治疗进展

结直肠癌肝转移是影响结直肠癌预后的重要因素，治疗方案包括手术治疗、化疗（全身静脉化疗和介入治疗）、基因治疗和局部治疗（射频消融、激光消融、无水酒精注射和冷冻切除术）等，其中手术是目前唯一有效的治愈手段，手术死亡率1％～2．8％，术后5年生存率34％-38％，但仅有10％．25％结直肠癌肝转移患者确诊时适合于手术切除，因此各种非手术治疗的作用正日益受到关注。本文对结直肠癌肝转移的综合治疗作一综述。     

结直肠癌肝转移治疗进展

结直肠癌肝转移是影响结直肠癌患者生存率的主要原因，目前对其治疗尚无最佳方案。肝叶切除术是治疗肝转移癌的“金标准”，对于3个以下的肝脏转移灶，行肝叶切除术是最佳选择。而对于无手术指征的肝转移患者，使用去氧氟尿苷的肝动脉化疗可获得较高的缓解率。随着生理周期化疗、基因治疗、射频消融治疗、肝血流阻断灌注治疗等方法的发展，结直肠癌肝转移患者的治愈率有望获得提高。     

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer

Background:

In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS).

Methods:

In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment.

Results:

From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1% complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001).

Conclusions:

FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.     

肝移植在结直肠癌肝转移中的价值

结直肠癌是全球范围内发病率和死亡率均高的恶性肿瘤之一,早期容易发生转移,而肝脏恰是结直肠癌远处转移的最常见器官.随着肝移植技术的发展与进步,不可切除性结直肠癌肝转移患者获得了长期生存的新机遇.近年来,挪威奥斯陆大学医院在肝移植治疗不可切除性结直肠癌肝转移的领域中取得了一系列巨大突破,引起了世界各地学者的广泛关注.随后,...     

结直肠癌肝转移术后化疗远期疗效的Meta分析

目的用Meta分析的方法,评价化疗对可切除结直肠肝转移患者长期疗效的影响。方法检索1990-01-2013-12发表于PubMed、Embase、Cochrane Library和万方数据库中收集化疗对可切除结直肠肝转移患者长期疗效随机对照试验的文章,有2名评价员独立按照纳入及排除标准,筛选及提取数据并评估研究的方法学质量,利用Cochrane协作网提供的RevMan 5.1.4软件进行Meta分析。结果共纳入8篇随机对照试验,样本量885例,手术+化疗组409例,单纯手术组476例。Meta分析结果显示,与单纯手术组患者相比,手术+化疗组患者并不具备长期生存的优势,两组差异无统计学意义,HR=0.92,95%CI为0.80~1.06,P=0.25,I2=17%。但在亚组分析中,手术+静脉化疗组与单纯手术组相比,两组差异有统计学意义,HR=0.80,95%CI为0.63~1.00,P=0.05,I2=0;手术+肝动脉化疗组与单纯手术组相比,两者差异无统计学意义,HR=1.00,95%CI为0.84~1.21,P=0.96,I2=30%。在分析无疾病进展时间时,化疗组可以增加患者的无疾病进展时间,HR=0.77,95%CI为0.67~0.88,P=0.000 2,I2=25%。在亚组分析中,手术+静脉化疗组(HR=0.75,95%CI为0.62~0.92,P=0.004,I2=0)与单纯手术组相比差异有统计学意义,但手术+肝动脉化疗组与单纯手术组差异无统计学意义,HR=0.72,95%CI为0.51~1.02,P=0.07,I2=54%。结论全身静脉化疗对于提高和改善结直肠癌肝转移手术患者的长期生存及无疾病进展时间是有帮助的,但静脉化疗的时间及方案选择还需大样本前瞻性研究进一步证实。     

大肠癌伴肝转移患者的预后因素

目的探讨影响大肠癌伴肝转移患者预后的因素.方法1995年5月-1999年12月间本院外科手术治疗的64例大肠癌伴肝转移患者,部分患者全身化疗或肝动脉插管化疗,并对其临床资料进行统计分析.结果本组大肠癌肝转移患者占大肠癌患者10.2%.肝转移灶大小、术前CEA水平、原发灶切除、辅助治疗方式为影响生存的独立的预后因素.年龄、性别、肿瘤部位、分化程度、肝转移灶数目与预后无关.肝转移灶＞5cm、术前CEA＞100μg/ml、原发灶未切除的患者的生存时间(3.52月)显著低于其他患者(21.60月).结论治疗方式对肠癌肝转移患者预后影响显著,应积极切除原发灶、治疗转移灶.肝动脉插管化疗优于全身化疗.肝转移灶大小、术前CEA水平是重要的预后指标.     

Liver metastases from colorectal cancer: Technique of liver resection

Liver resection has become standard for the treatment of metastatic colorectal cancer (CRC): anterior approach, hanging manoeuvre, or total vascular exclusion techniques as well as 3‐dimensional imaging enable safe resections even in difficult cases. Furthermore, modern chemotherapy, portal vein embolization/ligation, and two‐stage procedures increase the resectability of metastasis, and repeat resections are feasible for recurrence. In addition to characteristics of the primary, CEA, extent of metastasis, resection margins, and extrahepatic disease, hilar lymph node metastases appear prognostic. J. Surg. Oncol. 2013;107:579–584. © 2012 Wiley Periodicals, Inc.     

Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer

BACKGROUND:

The optimal combination of available therapies for patients with resectable synchronous liver metastases from rectal cancer (SLMRC) is unknown, and the pattern of recurrence after resection has been poorly investigated. In this study, the authors examined recurrence patterns and survival after resection of SLMRC.

METHODS:

Consecutive patients with SLMRC (disease‐free interval, ≤12 months) who underwent complete resection of the rectal primary and liver metastases between 1990 and 2008 were identified from a prospective database. Demographics, tumor‐related variables, and treatment‐related variables were correlated with recurrence patterns. Competing risk analysis was used to determine the risk of pelvic and extrapelvic recurrence.

RESULTS:

In total, 185 patients underwent complete resection of rectal primary and liver metastases. One hundred eighty patients (97%) received chemotherapy during their treatment course, and 91 patients (49%) received pelvic radiation therapy either before (N = 65; 71.4%), or after (N = 26; 28.6%) rectal resection. The 5‐year disease‐specific survival rate was 51% for the entire cohort with a median follow‐up of 44 months for survivors. One hundred thirty patients (70%) developed a recurrence: Eighteen patients (10%) had recurrences in the pelvis in combination with other sites, and 7 of these (4%) had an isolated pelvic recurrence. Recurrence pattern did not correlate with survival. Competing risk analysis demonstrated that the likelihood of a pelvic recurrence was significantly lower than that of an extrapelvic recurrence (P < .001).

CONCLUSIONS:

Of the patients with SLMRC who developed recurrent disease, systemic sites were overwhelmingly more common than pelvic recurrences. The current results indicated that the selective exclusion of radiotherapy may be considered in patients who are diagnosed with simultaneous disease. Cancer 2012. © 2012 American Cancer Society.