肝动脉灌注在结直肠癌肝转移治疗中的应用现状及前景

肝转移是结直肠癌主要的转移模式及治疗关键。相对于全身化疗,肝动脉灌注（hepatic arterial infusion, HAI）给药方式可使肝脏局部药物浓度升高,而外周血液中药物浓度较低,全身不良反应相对较低。《中国肿瘤临床》于2015年第20期邀请中山大学肿瘤防治中心李宇红教授综述了肝动脉灌注化疗在结直肠癌肝转移的转化化疗、肝切除术后辅助治疗及结直肠癌根治性切除术后的肝转移预防方面的作用与价值。     

肝动脉药盒灌注氟脲苷联合全身化疗治疗不可切除老年结直肠癌肝转移

目的 探讨经肝动脉药盒灌注（HAI）氟脲苷（FUDR）联合全身化疗治疗不可切除老年结直肠癌肝转移患者的疗效及安全性.方法 对18例不可手术切除的老年结直肠癌肝转移回顾性分析.所有患者采用一种改进的介入方法植入肝动脉药盒,术后第2天开始接受HAI FUDR联合全身化疗.对治疗疗效、毒副反应及随访结果进行分析.结果 18例患者的总有效率为94.4%,其中完全缓解1例（5.6%）,部分缓解16例（88.9%）,疾病进展1例（5.6%）.8例患者转化为可手术切除,转化率为44.4%.中位无进展生存时间为26.0个月,中位总生存时间为30.2个月.结论 HAI FUDR联合全身化疗是治疗不可切除老年结直肠癌肝转移的一种安全有效的方法,可获得较高的手术切除率.     

肝动脉灌注化疗治疗胃癌同时多发性肝转移的疗效观察

 目的 评估肝动脉灌注化疗（HAI）联合姑息性胃切除术治疗胃癌同时多发性肝转移的疗效。 方法 按治疗方法不同将29例胃癌同时多发性肝转移患者分为HAI组和non-HAI组,回顾性分析HAI化疗的疗效。 结果 HAI化疗后CR4例,PR7例,有效率78.6%; HAI组的中位生存期为13.7月,non HAI组中位生存期为9.4月,经Log rank检验,差异有统计学意义（P＜0.05）。 结论 HAI化疗能有效控制胃癌同时多发性肝转移患者的转移灶,可作为此类患者的治疗选择。     

肝癌化疗的研究进展

尽管有各种治疗模式，不能切除肝细胞癌(UHCC)仍存在较差的自然病程，其治疗主要集中在化疗和化疗相关治疗。全身化疗和化疗相关治疗如肝动脉栓塞化疗(TACE)、肝动脉灌注化疗(HAI)、经皮注射化疗(PICT)和化学药物预防等，近年来发展迅速并有广阔的应用前景。     

大肠癌肝转移86例外科综合治疗

 目的 探讨大肠癌肝转移外科综合治疗的方法及临床效果。方法 对86例大肠癌肝转移患者均在行大肠癌根治术的同时，分别配合部分肝切除、全身静脉化疗、介入化疗、无水酒精注射、腹腔化疗泵植入等方法进行治疗。结果 本组74例原发癌位于左半或右半结肠，12例原发癌位于直肠，肝转移灶发生在左半结肠者明显多于右半结肠者，两组差异有极显著性（P＜0.01）；在综合治疗中，以左、右半结肠癌根治性切除（R2-R3）+肝转移癌部分肝切除术+静脉化疗组疗效较佳，其3年生存率明显高于其他组，差异有极显著性（P＜0.01）。而各组间五年生存率无显著差异（P＜0.05）。结论 大肠癌肝转移患者，视肝转移灶在肝内的部位，大小，多少进行合理的综合治疗，能提高病人的生存质量和生存期。     

肝癌化疗的研究进展

尽管有各种治疗模式,不能切除肝细胞癌(UHCC)仍存在较差的自然病程,其治疗主要集中在化疗和化疗相关治疗.全身化疗和化疗相关治疗如肝动脉栓塞化疗(TACE)、肝动脉灌注化疗(HAI)、经皮注射化疗(PICT)和化学药物预防等,近年来发展迅速并有广阔的应用前景.     

肝动脉灌注化疗与全身化疗治疗胃肠道肿瘤肝转移的对比分析

目的：比较肝动脉灌注化疗与全身化疗治疗胃肠道肿瘤肝转移癌的疗效和毒副作用。方法：60例病人被随机分成动脉灌注组（30例）和全身化疗组（30例），动脉灌注组：25例病人施行肝动脉化疗药灌注并行肿瘤供血动脉栓塞，5例病人单纯肝动脉药物灌注，化疗方案：亚叶酸钙＋氟尿嘧啶＋羟基喜树碱＋顺铂。全身化疗组：化疗药同动脉灌注组。结果：与全身化疗组比较，动脉灌注组近期有效率、半年和1年生存率明显提高，统计学分析有明显差异（P〈0．05），治疗进展时问、中位生存时间、3年生存率无明显差异（P〉0．05），恶心呕吐、腹泻、脱发的发生率显著减少（P〈0．01），白细胞减少、口腔炎显著减少（P〈0．05）。结论：与全身化疗比较，肝动脉灌注化疗对治疗胃肠道肿瘤肝转移癌效率高、副作用轻、生存情况明显改善。     

大肠癌肝转移的治疗体会（附28例报告）

自1989年－1995年共收治28例大肠癌肝转移的病人，在大肠癌根治的基础上，采用各种方法治疗肝转移癌，取一定疗效，其中行肝叶切除4例，肝动脉结扎置管化疗和门静脉属支置管化疗10例，放射介入肝动脉栓塞化疗8例，B超引导下无水酒精注射5例，全身化疗加免疫治疗1例，均不同程度革延长了生存期。大肠癌发生肝转移癌的发生率较高，如能早期发现并予以切除，可获得较好的疗效，影响手术切除的因素有（1）手术的时机；（2）肝脏切除量；（3）适宜的手术指征。肝切除以外的其它治疗方法如全身化疗加免疫疗法，对于不能手术的弥散型肝转移癌仍不失为较好的治疗方法。     

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。     

初始可切除结直肠癌肝转移术后辅助化疗的研究进展

结直肠癌是目前全球第三大常见的恶性肿瘤，大约有50%的患者在病程中发生肝转移。结直肠癌肝转移(CRLM)分为初始可切除和不可切除。肝切除术目前被认为是治疗CRLM唯一潜在的治愈方法，患者5年生存率约为37%～40%。但肝切除术后这部分患者仍然存在较高的复发风险，因此选择合适的辅助治疗尤为重要。目前CRLM患者术后辅助化疗存在争议，以往前瞻性临床研究发现术后辅助化疗能延长无进展生存时间，但无法改善总生存时间。最近部分研究在化疗基础上联合靶向药物或肝动脉灌注化疗(HAIC)等应用于术后CRLM患者，以期获得更好的疗效。本文就可切除CRLM术后辅助化疗的应用现状及研究进展作一综述。     

Chemotherapy for liver metastasis of colorectal cancer

In colorectal cancer, liver metastasis is the most common and most important prognostic factor. Although surgical resection is the first choice of treatment for liver metastasis of colorectal cancer, there are many cases we cannot choose the surgical treatment. The chemotherapy is very important in such cases. We examined 18 cases of unresectable liver metastases from colorectal cancer which were adapted a hepatic arterial infusion of 5-FU (HAI) with a weekly high-dose infusion method (WHF) as the first-line treatment, and then systemic chemotherapy of CPT-11 in combination with 5-FU as the second-line treatment. The response rate of this treatment is 72% (13/18) and the 1-, 2-, 3-year survival rates were 100% (16/16), 83% (10/12), and 50% (5/10), respectively. The combination chemotherapy of HAI with systemic chemotherapy using CPT-11 seemed to be an effective treatment method.     

Hepatic artery infusion in the treatment of colorectal cancer metastases

The most common site of metastasis from colorectal carcinoma is the liver. Surgical resection of hepatic metastases can result in long-term survival. The majority of patients have unresectable disease, however, and even if hepatic metastases are resected, most patients will still experience relapse, often in the liver. Hepatic arterial infusion (HAI) of chemotherapy allows high concentrations of a drug to be delivered directly to hepatic metastases with minimal systemic toxicity. HAI therapy has been used to treat unresectable isolated hepatic metastases of colorectal cancer and has also been investigated as adjuvant therapy after resection. This review examines the role of HAI as therapy for both unresectable and resectable hepatic metastases.     

Adjuvant hepatic arterial infusion after resection of hepatic metastasis from colorectal cancer

We examined retrospectively the efficacy of hepatic arterial infusion (HAI) chemotherapy comparing systemic treatment as adjuvant therapy after the curative resection of hepatic metastasis from colorectal cancer. Seventeen cases of HAI and 8 of the systemic treatment were enrolled in this study. We compared the pattern of recurrent sites and the overall survival rate between the two groups. There was no difference in a patients' background. Intrahepatic recurrence rate was lower and extrahepatic recurrence rate was higher in the HAI group, but not significant. The 1-, 3-, and 5-year overall survival rate was 94, 72, and 49% in the HAI group and 100, 100, and 50% in the systemic treatment group (p = 0.29), respectively. HAI chemotherapy did not contribute to the elongation of survival time in comparison with systemic treatment. This study indicates that there is no efficacy of HAI alone after the resection of hepatic metastasis from colorectal cancer and that there is need to use systemic chemotherapy together with HAI to prevent an extrahepatic recurrence.     

Systemic chemotherapy for advanced colorectal cancer with liver metastasis

We report the progress of systemic chemotherapy for advanced colorectal cancer with liver metastasis. It must be noted that the purpose of this treatment is to prolong the symptom-free period. Review of hepatic arterial infusion (HAI) compared with systemic chemotherapy for the treatment of unresectable liver metastases from colorectal cancer showed that was attained with HAI a much higher response rate and survival benefit than systemic chemotherapy. However, systemic chemotherapy has shown progress since that time. Regarding administration methods, continuous injection is better than bolus injection for 5-FU. New modulators of 5-FU have also became available, such as leucovorin, CPT-11, and I-OHP. Futhermore, many studies of 5-FU-based combination therapy have shown that the mean survival time (MST) and response rate (RR) are now close to those of HAI. Finally, the combination with HAI with systemic chemotherapy using CPT-11 resulted in the highest RR of 74%. Further trials of such combination therapy will be performed in the future.     

Regional chemotherapy: a focus on hepatic artery infusion for colorectal cancer liver metastases

Regional infusion strategies have been used as a treatment modality in multiple cancers, including ovarian, appendiceal, and colorectal cancers. Perhaps the most illustrative use of regional therapy is that of hepatic arterial infusion (HAI) for liver metastases from colorectal cancer. The administration of chemotherapy by HAI is logical and has theoretic advantages over systemic chemotherapy for the treatment of hepatic metastases from colorectal cancer. With the use of an appropriately chosen chemotherapy agent, HAI can generate an increase in hepatic tumor drug exposure as compared with intravenous delivery of the same agent. This article reviews the pharmacologic benefits of HAI therapy and the contemporary trials performed and underway.     

Hepatic arterial infusion of chemotherapy for hepatic metastases from colorectal cancer.

BACKGROUND: Sixty percent of colon cancer patients develop liver metastasis. Only 25% of those have potentially resectable hepatic metastases, and approximately 58% of those patients relapse. METHODS: We review the indications and the technical aspects of hepatic artery infusion (HAI) of chemotherapy, as well as the efficacy, morbidity, and outcomes. RESULTS: HAI of chemotherapy has been used following hepatic metastasectomy, in patients with unresectable metastases, or in combination with other agents. Floxuridine, the chemotherapeutic agent most studied, is administered through an implantable subcutaneous infusion pump connected to a surgically placed hepatic artery catheter, which delivers the chemotherapeutic agents at a slow fixed rate. Treatment-related toxicities include chemical hepatitis, biliary sclerosis, and peptic ulceration. Some trials report a survival benefit for HAI over systemic chemotherapy with acceptable toxicity. CONCLUSIONS: Regional perfusion chemotherapy can be logistically and technically complicated to deliver. The development of newer systemic agents with superior efficacy in the treatment of metastatic colorectal cancer will likely diminish the role of regional perfusion therapy in the future.     

Hepatic arterial infusion chemotherapy for colorectal liver metastases

Hepatic metastases are a frequent complication of colorectal cancer. Resection of liver metastases can result in long-term survival. However, the majority of patients have unresectable disease. Alternative methods in Japan for treating these patients are hepatic arterial infusion (HAI) chemotherapy with administration of 1,000 mg/m2 of 5-FU over 5 hours. We summarize the status of HAI chemotherapy in terms of colorectal hepatic metastases today. HAI chemotherapy produced higher response rates compared with systemic chemotherapy, but did not demonstrate elongation of survival time in many trials. Important problems remaining to be solved are the technical aspects of percutaneous implantation of intraarterial catheters connected to a subcutaneous infusion reservoir and studies of combined therapy with systemic chemotherapy. Furthermore, in order to finally determine the position of HAI for colorectal liver metastases, it is necessary to conduct a comparative study versus systemic chemotherapy, using the survival time as the primary end point.     

Hepatic artery infusion of chemotherapy following resection of liver metastases

Conclusions HAI chemotherapy, when added to systemic chemotherapy following resection of liver metastases, significantly reduces the risk of hepatic progression of colorectal cancer and results in a greater proportion of patients surviving 2 years after resection. However, median overall survival and median overall progression-free survival are not significantly improved by the addition of HAI chemotherapy. The addition of HAI chemotherapy produces greater toxicity and a higher rate of hospitalization for management of toxicity. Better systemic chemotherapy is still sorely needed to optimize the management of patients with metastatic colorectal cancer.     

Prehepatectomy chemotherapy using hepatic artery infusion plus systemic chemotherapy for liver metastases from colorectal cancer

The purpose of this study was to determine the efficacy of hepatic artery infusion (HAI) plus systemic chemotherapy (SYS) as the prehepatectomy chemotherapy for liver metastases from colorectal cancer. Clinicopathologic data were available for 117 patients who were treated with chemotherapy before liver surgery. Response rate of chemotherapy and frequency of liver resection after chemotherapy of patients treated with HAI/SYS (n=26; 65% and 96%, respectively) were higher than those treated with HAI alone (n=63; 41% and 70%) or SYS alone (n=28; 25% and 42%). Histological examination of adjacent nonneoplastic liver confirmed that severe sinusoidal dilatation was less frequent in HAI/SYS group than in SYS group, and moderate to severe steatosis was also less frequent in HAI/SYS group as compared to HAI group. The combination of regional HAI and systemic chemotherapy is an effective prehepatectomy regimen for the treatment of patients with aggressive liver metastases from colorectal cancer.     

Regional and systemic chemotherapy for primary hepatobiliary cancers and for colorectal cancer metastatic to the liver

Hepatic arterial infusional (HAI) chemotherapy is based on the premise that primary and metastatic tumors derive their blood supply from the hepatic artery, whereas normal liver derives its blood supply from the portal vein. This approach has been extensively studied in liver-only colorectal metastasis patients, with 10 published prospective randomized clinical trials comparing fluoropyrimidine-based HAI therapy with systemic chemotherapy. Most of these studies showed a statistically significant superior response rate and improved disease-free survival with HAI chemotherapy compared with systemic fluoropyrimidine-based chemotherapy alone. More advanced chemotherapeutic regimens including biologically targeted agents have clearly impacted survival in metastatic colorectal cancer patients and are currently under investigation with HAI-based trials. In contrast, hepatobiliary tumors remain difficult to treat with overall poor response and survival with systemic chemotherapy. Few clinical trials have attempted to address the role of HAI-based therapy for these regional tumors, although encouraging response rates up to 60% have been reported. Therefore, the regional approach for hepatobiliary tumors deserves further investigation as well as randomized trials for adequate comparison to new systemic chemotherapies.