220例结直肠癌同时肝转移患者临床预后分析

背景与目的:结直肠癌是国内常见的肿瘤之一,结直肠癌同时肝转移的发生率可高达10%～25%。本文探讨影响结直肠癌同时肝转移患者预后的因素和治疗的选择。方法:回顾性分析1995年12月至2002年12月中山大学肿瘤防治中心收治的初治结直肠癌同时肝转移患者220例,对其临床资料进行统计分析。用Kaplan-Meier法对结直肠癌同时肝转移患者的预后进行单因素分析,用Cox模型进行多因素分析。结果:本组病例5年生存率为5.52%,中位生存时间为12.93个月。用Kaplan-Meier及log-rank法对临床特征进行单因素生存分析,有统计学意义的变量因素包括:肝转移灶数目、肝转移灶最大径、肝转移灶分布、肝外是否存在侵犯或转移、确诊时CEA水平、局部区域淋巴结有无转移、病理类型。对临床治疗方式进行单因素生存分析,有统计学意义的变量因素包括:治疗方式、原发灶是否完全切除和化疗方案的选择。用Cox模型进行多因素分析后发现:肝转移灶分布肝叶数、肝转移灶最大径、肝外是否存在侵犯或转移、确诊时CEA水平、治疗模式、原发病灶是否切除、化疗方案为独立的预后危险因素。结论:对于结直肠癌同时肝转移的患者,肝转移灶最大直径超过5cm、肝转移灶分布超过一叶、存在肝外侵犯或转移灶和CEA水平超过200μg/L提示患者预后不良。对于仅有肝转移的结直肠癌患者应尽可能手术根治原发灶以及转移灶,对于手术不能切除的肝转移灶可考虑行全身化疗和/或介入治疗,全身化疗最好选用含草酸铂的方案。     

不同治疗方法对结直肠癌肝转移患者预后的影响

目的 探讨不同治疗方法对结直肠癌肝转移患者预后的影响.方法 对300例结直肠癌首发肝转移患者的诊治过程及肝转移后生存情况进行回顾性分析.结果 结直肠癌肝转移灶完全切除者、姑息切除者和无法切除者的肝转移后中位生存期分别为48、19和18个月(P=0.000).对于无法行肝转移灶完全切除的患者,肝转移后化疗联合局部治疗和不治疗患者的肝转移后中位生存期分别为23个月和6个月(P=0.000).一线治疗有效患者和无效患者的肝转移后中位生存期分别为24个月和16个月(P=0.000).单因素生存分析结果显示,原发肿瘤的治疗方式、肝转移灶的手术方式、肝转移后的综合治疗以及一线治疗的疗效均与预后相关(均P<0.05).多因素分析结果显示,肝转移灶的手术方式、肝转移后的综合治疗和肝转移后一线治疗的疗效是影响结直肠癌肝转移患者预后的独立因素(P<0.05).结论 肝转移灶完全切除、肝转移后进行综合治疗以及肝转移后一线治疗有效的结直肠癌肝转移患者预后好.     

结直肠癌局限性肝转移的治疗

[目的]探讨结直肠癌局限性肝转移多种治疗方法的价值。[方法]对我院1987年-2000年收治的原发癌根治术后的引例结直肠癌局限性肝转移患者进行回顾性研究。[结果]原发癌加肝转移灶切除患者1、3、5年生存率分别为85.7％、46.9％、32.1％,而肝转移灶未治疗的患者分别为26.7％、0、0,两者的差异均有显著性（P<0.05）;肝转移灶微波固化和无水酒精注射及肝脏区域化疗合并组患者1、3、5年生存率分别为 74.2％、42.9％、19.2％,其与肝转移灶切除组的差异均无显著性（P>0.05）,与肝转移灶未治疗组的1、3年生存率差异有显著性（P<0.05）。[结论]1结直肠癌局限性肝转移患者,应尽可能彻底切除原发癌和肝转移灶,肝转移灶微波固化和无水酒精注射及肝脏区域化疗是其治疗的重要补充。     

结直肠癌切除同期射频消融肝转移的临床应用

肝脏是结直肠癌转移的最常见部位。有10％～25％的患者初次就诊或外科治疗时就发现肝转移，约20％的患者在结直肠癌手术后的一段时期发生肝转移。不经治疗的肝转移癌患者中位生存期仅5～9个月。因此，对肝转移癌的有效治疗十分重要。我们对13例结直肠癌肝转移患者实施结直肠癌切除同期肝转移灶射频消融治疗，总结报道如下。     

结直肠癌肝转移患者临床预后的多因素分析

目的:探讨影响结直肠癌肝转移患者预后的相关临床病理因素及其治疗方法的选择.方法:回顾性分析贵州省肿瘤医院1997年3月-2007年3月收治的146例结直肠癌肝转移患者,对其相关的临床病理资料进行统计学分析,应用寿命表法计算生存率,绘制Kaplan-Meier生存曲线并应用log-rank检验对患者的临床病理特征及治疗方法进行单因素分析,应用COX回归模型进行多因素分析并计算预后指数(prognostic index, PI),根据PI值将患者分为不同的危险组,并比较各组的生存率.结果:全组总的1、3和5年生存率分别为62.0%、15.5%和6.2%.单因素分析显示,病理类型﹑肿瘤细胞分化程度、确诊时血清癌胚抗原(carcinoembryonic antigen,CEA)水平﹑是否有区域淋巴结转移、肝转移瘤大小及数目﹑肝转移灶分布、肝转移瘤诊断时间﹑是否合并肝外侵犯﹑肝转移灶是否手术﹑是否行化疗及化疗方案的选择等与结直肠癌肝转移患者的预后相关.多因素分析显示,确诊时血清CEA水平﹑有无肝外转移﹑肝转移瘤大小及数目﹑原发病灶切除和化疗方案为独立的预后影响因素.高危组﹑中危组和低危组患者生存率的两两比较,差异有统计学意义﹙P＜0.05﹚.结论:治疗方法的选择对结直肠癌肝转移患者的预后具有重要影响,积极治疗原发病灶及转移灶可提高患者的生存率.血清CEA水平﹑有无肝外转移﹑肝转移瘤大小和数目等因素与预后明显相关.PI值可用于结直肠癌肝转移患者的预后评估.     

结直肠癌肝转移诊治进展

肝转移是影响结直肠癌患者预后的主要因素。手术切除肝转移灶目前公认最有效治疗手可明显提高结直肠癌患者的生存率。原发肿瘤的生物学特性，肝转移灶的数量，手术切缘情况等因素可影响手术预后，肝转移灶切除术后复发再手术切除可进一步提高远期疗效。     

198例结直肠癌肝转移患者外科治疗的疗效分析

背景与目的:肝脏是结直肠癌常见的转移部位,35%的患者在确诊时已发生肝转移,肝转移患者的预后较差。尽管手术切除、化疗、射频消融术、介入治疗等手段应用于临床,但治疗效果不同。本研究探讨结直肠癌肝转移外科治疗的临床疗效。方法:对我院5年间经病理检查证实的198例结直肠癌肝转移患者的临床资料进行回顾性分析。根据治疗方法的不同进行分组:根治性切除组46例(23.2%)、姑息性切除组43例(21.7%)、手术探查组或最佳支持治疗组29例(14.6%)、肝动脉置泵化疗组41例(20.7%),全身化疗组39例(19.7%);对其生存期进行比较和统计学分析。结果:根治性切除组中位生存期37.1个月,5年生存率为31.2%;姑息性切除组的中位生存期14.3个月,5年生存率为0;肝动脉置泵化疗组的中位生存期21.3个月,5年生存期为7.5%;全身性化疗和探查组或最佳支持治疗组的中位生存期分别为18.7个月、6.3个月,均无5年生存者。根治性切除组与其他组比较,中位生存期有统计学意义(P<0.01)。结论:根治性切除是提高结直肠癌肝转移患者生存率的重要手段;姑息性切除治疗效果并不优于辅助性治疗,对于不能根治性切除的病例可采用肝动脉置泵化疗。     

选择性体内放疗对不可切除结直肠癌肝转移的治疗

结直肠癌在远处转移中肝转移比例达50％～75％,但只有10％～15％的肝转移患者能获得手术切除的机会,且易复发.选择性体内放疗(SIRT)是用于肝脏定向的新型放射疗法,对于不可切除的结直肠癌肝转移,该疗法单独或联合其他疗法可缩小癌灶,延长患者生存期,并可能改善总生存率.     

新辅助化疗在结直肠癌肝转移治疗中的作用

目的 探讨新辅助化疗在结直肠癌肝转移治疗中的作用。方法 选取76例接受新辅助化疗的结直肠癌肝转移患者,观察新辅助化疗前后原发灶及肝转移灶大小、血清CEA水平变化情况,分析其根治性手术切除率、化疗不良反应、手术并发症以及根治性手术切除患者及其他治疗方式患者的2年生存情况。结果 新辅助化疗后,大部分患者原发灶、肝转移灶体积明显缩小,血清CEA水平明显下降,与接受新辅助化疗前相比,差异有统计学意义（P＜0.05）。其中肝转移灶获CR 0 例,PR 51 例, SD 24 例, PD 1例, 有效率为66.11%（51/76）;原发灶获CR 0 例,PR 44 例, SD 30例, PD 2例, 有效率为57.89% （44/76）。新辅助化疗不良反应以周围神经炎、消化道反应、骨髓抑制等为主,多为Ⅰ～Ⅱ级,未出现Ⅳ级不良反应。根治性手术切除率为30.26%（23/76）,手术并发症发生率为3.95%（3/23）。Kaplan-Meier生存分析显示,行根治性手术切除的结直肠癌肝转移患者2年生存情况显著优于其他治疗方法的患者（P＜0.05）。结论 新辅助化疗应用于肝转移灶潜在可切除的结直肠癌肝转移患者,使部分患者肝转移灶缩小,提高根治性手术切除率,改善预后,不良反应可耐受,是一种安全、有效的治疗方法。     

伴有同时性肝转移结直肠癌的外科治疗

目的探讨伴有同时性肝转移结直肠癌的外科治疗及其适应证。方法收集经外科手术治疗的116例伴有同时性肝转移的结直肠癌患者的临床资料,进行生存分析,并通过单因素分析和Cox比例风险模型多因素分析确定患者预后的影响因素。结果116例患者均行结直肠癌原发肿瘤切除,18例行同期肝转移瘤切除。围手术期死亡2例(1.7%),术后发生并发症者17例(14.7%)。全组患者5年生存率为14.29%,肝转移瘤切除患者5年生存率为32.12%。多因素分析显示,肝转移瘤切除、腹腔扩散、介入治疗和全身化疗是影响预后的最主要因素。结论伴有同时性肝转移的结直肠癌患者,选择外科手术切除肿瘤病灶,并辅助综合治疗可延长患者的生存时间。     

Successful treatment with cetuximab combination chemotherapy in a case of FOLFOX-refractory rectal cancer with previously unresectable multiple liver metastases leading to complete resection

Most colorectal cancer patients with liver metastases are not resectable upon initial diagnosis. Recently, chemotherapy improves overall survival of initially unresectable patients by allowing tumor downstaging and complete resection. We report a FOLFOX-refractory rectal cancer patient with unresectable multiple liver metastases, whose tumors could be downstaged and completely resected after initiation of FOLFIRI with cetuximab. Case: A 41-year-old male demonstrated rectal cancer with unresectable multiple liver metastases. He was treated by FOLFOX4 therapy as first-line chemotherapy. After initiating 14 courses, he was treated by FOLFIRI with cetuximab because of disease progression. After initiation of chemotherapy, radiographic examination demonstrated remarkable reduction of primary rectal tumor and metastatic liver tumors. He underwent complete rectal tumor resection after 13 courses of chemotherapy, and metastatic liver tumor resection after 18 courses of chemotherapy.     

Progress in metastatic colorectal cancer: growing role of cetuximab to optimize clinical outcome

The prognosis of metastatic colorectal cancer remains poor despite advances made in recent years, particularly with new treatments directed towards molecular targets. Cetuximab, a chimeric immunoglobulin (Ig)G1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer. As an IgG1 antibody, cetuximab may exert its antitumour efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The benefits of cetuximab in metastatic colorectal cancer are well documented in clinical trials and are acknowledged in the approval and licensing of this agent. There is evidence of the role of cetuximab not only in irinotecan-refractory or heavily pretreated patients, but also of the efficacy and safety of the addition of this agent to FOLFIRI (irinotecan/5-fluorouracil/leucovorin) in first-line metastatic colorectal cancer, with an enhanced effect in 5-fluorouracil patients with Kirsten rat sarcoma (KRAS) wild-type tumours. In these patients, a recent meta-analysis of the pooled Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) and Oxaliplatin and Cetuximab in First-Line Treatment of mCRC (OPUS) patient populations confirms that the addition of cetuximab to first-line chemotherapy achieves a statistically significant improvement in the best overall response, overall survival time, and progression-free survival (PSF) compared with chemotherapy alone. In nonresectable colorectal liver metastases, cetuximab plus FOLFOX-6 (oxaliplatin/5-fluorouracil/leucovorin) or cetuximab plus FOLFIRI increased significantly resectability of liver metastases, including R0 resections. Also, preliminary data indicate that cetuximab can be administered in a more convenient 2-week schedule in combination with standard chemotherapy. Cetuximab is generally well tolerated. Acne-form rash is the most frequent toxicity. Up to the present time, the results obtained with targeted therapy combinations are not as encouraging as initially expected. The identification of biomarkers associated with disease control, including KRAS and BRAF mutation status in patients treated with cetuximab, is changing the current management of metastatic colorectal cancer. Clinical and molecular predictive markers of response are under active evaluation in order to better select patients who could benefit from cetuximab treatment, with the aim of both optimising patient outcomes and avoiding unnecessary toxicities.     

Do we need biologic agents in preoperative systemic therapy of liver metastases?

Liver metastases from colorectal cancer are common in patients who present with an initial diagnosis of metastatic disease or in those with recurrence. Without treatment, patients with metastatic disease have a poor prognosis. However, with surgical resection of the metastases, many patients may have the opportunity for long-term survival. The use of chemotherapy in patients undergoing surgery has augmented the long-term survival benefits that are gained with surgery. The use of preoperative chemotherapy may convert a portion of initially unresectable liver metastases to resectable ones. A growing body of literature is helping to define the role of chemotherapy in this setting. The introduction of newer biologic agents (eg, cetuximab and bevacizumab) has led to meaningful improvements in response rates and survival for metastatic colorectal cancer patients. However, further trials are required to better determine the benefits of chemotherapy and biologic agents in the management of patients with liver metastases.     

FOLFOX plus cetuximab for a patient with metastatic colorectal cancer with icterus due to multiple liver metastases

The prognosis of patients with advanced colorectal cancer with icterus is dismally poor, and adequate chemotherapy for these patients has not been established yet. A 59-year-old male with fatigue, anorexia and icterus with serum total bilirubin 9.7 mg/dL was referred to our institution. He was diagnosed with advanced sigmoid colon cancer with multiple liver metastases. A biopsy specimen of the primary tumor showed well-differentiated adenocarcinoma without KRAS mutation. Since biliary drainage was impossible due to diffuse liver metastases, we initiated combination chemotherapy with 5-fluorouracil, Leucovorin, oxaliplatin (modified FOLFOX6) and cetuximab. The doses of 5-fluorouracil and oxaliplatin were reduced, but cetuximab was administered at the standard dosage. After 3 courses of chemotherapy, total bilirubin dropped to 0.8 mg/dL. No significant toxicity other than grade-2 skin toxicity and neuropathy was observed, and the patient has continued chemotherapy on an outpatient basis. Combination chemotherapy with mFOLFOX6 plus cetuximab was effective and feasible in this case of metastatic colon cancer with icterus due to diffuse liver metastasis.     

大肠癌肝转移的治疗策略与进展

肝脏转移是大肠癌(CRC)最常见远处转移器官和主要死亡原因,对于适合手术治疗的肝挝脏转移,手术是首选的方法,不能手术治疗的则应该选择化疗、靶向治疗、肝动脉介入化疗、放射治疗和射频或冷冻消融治疗.CRC肝转移的治疗要有整体观念,同时要注重局部治疗.     

西妥昔单抗单周和双周方案治疗晚期大肠癌的对比研究

 目的　比较西妥昔单抗250 mg／m2单周方案和500 mg／m2双周方案分别联合化疗治疗晚期大肠癌的近期疗效及安全性。方法　56例晚期大肠癌患者,ECOG行为状态评分0～2分,均有可评价病灶（RECIST 2000标准）。西妥昔单抗单周方案联合化疗组30例,给药方法为400 mg／m2第1周,以后250 mg／m2每周重复应用;双周方案联合化疗组26例,给药方法为500 mg／m2第1周,以后每两周重复应用。两组均以完成8周治疗或出现疾病进展为治疗终点。结果　西妥昔单抗单周方案联合化疗组28例可评价疗效：完全缓解（CR）1例,部分缓解（PR）7例,疾病稳定（SD）11例,疾病进展（PD）9例,有效率28.6 %,疾病控制率67.9 %;双周方案联合化疗组26例可评价疗效：CR 0例,PR 8例,SD 9例,PD 9例,有效率30.8 %,疾病控制率65.4 %,两组比较差异无统计学意义（P＞0.05）。两组Ⅲ～Ⅳ度不良反应主要表现为皮疹、恶心、中性粒细胞减少及白细胞减少,两组比较差异也无统计学意义（P＞0.05）。结论　西妥昔单抗单周和双周方案分别联合化疗治疗晚期大肠癌疗效相近,不良反应均可耐受。     

Portal venous gas following chemotherapy for colorectal cancer liver metastasis

The standard of care for patients with colorectal liver metastases is a combination of chemotherapy and surgery. New chemotherapy regimens with biologic agents (cetuximab, bevacizumab) have been shown to increase tumor response rates. Although this might be beneficial and this is an expected endpoint, it should be noted that patients with synchronous colorectal and liver metastases are at risk of septic complications. We recently encountered a case of hepatic portal venous gas after two cycles of chemotherapy in a patient with right colon cancer liver metastases. Complete necrosis of the liver metastasis subsequently turned into a liver abscess, which fistulized in the right portal vein. Infection of the necrotized metastasis was thought to be promoted by the colic tumor. Although this is a dramatic situation, it does not contraindicate a curative surgical resection.     

A case report of conversion therapy for initially unresectable colorectal cancer liver metastases after cetuximab as third-line treatment

The introduction of monoclonal antibodies into the treatment protocols for metastatic colorectal cancer(mCRC)has significantly improved outcomes. There are some patients with mCRC, initially judged unresectable, who become resectable after chemotherapy. For patients with isolated liver metastases, surgical resection is recommended when feasible. We experienced a case in which an initially unresectable mCRC liver metastases converted into a resectable one after cetuximab monotherapy as third-line treatment. The sample from hepatectomy was a pathologically complete response; no remnants were detected. The management of liver metastases contributes to improvements in the clinical setting. For conducting a multimodal treatment of mCRC, the participation of various specialists such as medical oncologists, colorectal/hepaticsurgeons and diagnostic/therapeutic radiologists is indispensable. Furthermore, it is necessary to construct an evidence-based consensus on potentially resectable CRC liver metastases in each hospital.     

结直肠癌肝转移患者生存情况及预后因素分析

目的 探讨结直肠癌肝转移患者的生存情况及其预后相关因素.方法 采用Kaplan-Meier和多因素回归分析方法,分析112例有完整随访资料的结直肠癌肝转移患者的生存情况及影响预后的相关因素.结果 112例患者的中位生存时间为18.3个月,1、2、3和5年生存率分别为60.8%、35.0%、20.3%和4.8%.单因素分析显示,患者性别、年龄、原发肿瘤部位、化疗与否、肿瘤的病理类型与患者的总生存时间无关(P＞0.05),而原发肿瘤治疗方法、肝脏转移时间、原发肿瘤大体类型、肝脏转移灶手术与否和临床分期与患者的预后有关(P＜0.05).多因素回归分析显示,肝脏转移灶手术与否、原发肿瘤大体类型和临床分期是影响结直肠癌肝转移患者预后的主要因素(P＜0.05).结论 对于结直肠癌肝转移的患者应积极切除肝转移病灶,延长患者生存时间.