中国结直肠癌肝转移诊断和综合治疗指南（V2023）

肝脏是结直肠癌血行转移最主要的靶器官，结直肠癌肝转移是结直肠癌治疗的重点和难点之一。为了提高我国结直肠癌肝转移的诊断和综合治疗水平，自2008年起各学组联合编写《中国结直肠癌肝转移诊断和综合治疗指南》并后续进行多次修订，以期指导对结直肠癌肝转移患者进行全面评估，精准地制定个体化的治疗目标，开展综合治疗，达到预防肝转移发生、提高肝转移灶局部毁损率、延长长期生存和改善生活质量的目的。此次修订后的《中国结直肠癌肝转移诊断和综合治疗指南（V2023）》包括结直肠癌肝转移的诊断和随访、预防、多学科团队作用、手术及其他毁损治疗、可达到“无疾病证据”状态结直肠癌肝转移的新辅助和辅助治疗、无法达到“无疾病证据”状态结直肠癌肝转移的综合治疗等六部分，汇集总结国内外该领域的先进经验和最新成果，内容详尽，可操作性强。     

结直肠癌肝转移的外科治疗

结直肠癌患者容易出现肝转移,肝转移是影响结直肠癌患者预后的主要原因之一.手术是目前治愈结直肠癌肝转移的唯一方法.本文主要总结了近年来结直肠癌肝转移患者肝转移病灶的手术进展情况:包括通过新辅助化疗或分阶段肝切除等方法提高肝转移病灶的手术切除率、肝转移灶切缘对患者预后的影响、同时性结直肠癌肝转移患者手术时机的选择、腹腔镜下肝转移灶切除的影响及优势,肝移植在结直肠癌肝转移患者中的应用等.本文旨在结合结直肠肝转移的手术进展和患者的实际情况,为患者选择最佳的治疗方案,从而提高患者的生存时间.     

结直肠癌肝转移治疗的研究进展

结直肠癌肝转移的发生率和死亡率很高,是影响结直肠癌预后的重要因素.因此,找到合理的治疗方案显得尤为重要.目前手术切除仍被认为是唯一可能有效的治愈手段,但能手术根治的患者仅占少数.因此,随着医疗技术的发展,肝转移癌治疗经验的积累,多学科综合治疗理念逐渐被广泛应用,是确保结直肠癌肝转移患者获得最佳治疗策略的根本,亦是今后结直肠癌肝转移治疗的发展方向.多学科综合治疗方案包括手术切除、新辅助化疗、肝动脉化疗栓塞、放射疗法、射频消融术、冷冻疗法、无水乙醇注射术及中医药治疗等,一种或多种方法联合应用可明显提高患者的生存率并改善生活质量,本文对结直肠癌肝转移的综合治疗进展作一综述.     

结直肠癌肝转移的治疗

结直肠癌肝转移是结直肠癌患者最主要的致死原因之一。结直肠癌肝转移的治疗方法很多,手术切除是其中的标准治疗方法,此外还有一些非手术治疗的方法,此文就结直肠癌肝转移的相关治疗方法作一综述。     

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。     

结直肠癌肝转移的手术治疗进展

肝转移是结直肠癌患者的主要死亡原因之一。15％～25％的结直肠癌患者在发现原发灶的同时确定有肝转移,另外有25％的结直肠癌患者将来会出现异时性肝转移,其中20％-35％的患者肝脏为惟一转移部位。孤立性肝脏转移未经治疗的结直肠癌患者中位生存期为5～9个月。不过,临床上发现,某些比较早期的结直肠癌就已出现肝转移,分化比较好的结直肠癌似乎更容易发生肝转移。因此,结直肠癌出现肝转移并不意味着失去治愈机会。目前手术切除仍然是结直肠癌肝转移的主要治疗手段。现将其手术治疗进展情况综述如下。     

术前血清CEA、CA19-9、CA50联合检测在结直肠癌肝转移预测中的应用

目的研究术前血清CEA、CA19-9、CA50联合检测在结直肠癌肝转移预测中的应用价值。 方法选择2015年1月至2017年1月在中国医学科学院肿瘤医院接受手术治疗的结直肠癌患者316例为研究对象,其中结直肠癌伴有肝转移的患者158例作为实验组,并按照性别、年龄等匹配结直肠癌不伴有肝转移的患者158例作为对照组。对所有患者的术前血清癌胚抗原（CEA）、糖类抗原19-9（CA19-9）以及糖类抗原50（CA50）进行检测,采用单因素及多因素分析以上肿瘤标志物单独或联合检测在结直肠癌肝转移中的预测价值。 结果单因素及多因素分析结果表明,术前血清CEA、CA19-9、CA50升高与结直肠癌发生肝转移显著相关（P<0.05）,CEA、CA19-9、CA50单独预测结直肠癌肝转移的敏感度分别为62.7%、57.4%、67.1%;特异度分别为58.2%、53.5%、56.6%。CEA、CA19-9、CA50联合诊断预测直肠癌肝转移的敏感度和特异度分别为74.3%、76.3%。 结论术前血清CEA、CA19-9、CA50升高是结直肠癌肝转移的独立预测因素,但三者单独预测结直肠癌肝转移的敏感度和特异度均较低。三者联合检测对于预测结直肠癌肝转移的敏感度和特异度均较高,可以作为结直肠癌肝转移的预测模型。     

人肝转移结直肠癌微小核糖核酸表达谱的初步研究

目的 研究人肝转移结直肠癌、无肝转移结直肠癌中微小核糖核酸(miRNA)的表达谱,筛选与结直肠癌肝转移相关的miRNA.方法 收集25例手术切除结直肠癌标本液氮储存.分别选取3例无肝转移和3例肝转移结直肠癌组织,提取组织总RNA,采用illumina miRNA芯片技术检测两种组织中miRNA的表达,筛选两种不同组织中差异表达miRNA,采用实时定量PCR技术在全部结直肠癌组织中对芯片检测结果进行验证.结果 肝转移结直肠癌组织与无肝转移结直肠癌组织中miRNA表达有明显差异,与无肝转移结直肠癌组织相比,在肝转移结直肠癌组织中差异表达的miRNA有28个,其中4个上调,24个下调.肝转移结直肠癌组织中miR-139-3p表达量为1.75±0.40,较无肝转移上调(0.69±0.58,P<0.05),而miR-19a在肝转移中的表达量为0.39±0.20,较无肝转移下调(1.38±0.98,P<0.05),miRNA芯片结果与定量RT-PCR结果一致.结论 miRNA的异常表达可能与结直肠癌的肝转移有关,特异的miRNA表达谱可以为结直肠癌的肝转移提供新的诊断和治疗靶点.     

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。     

结直肠癌远隔转移的治疗策略

世界范围内结直肠癌发病率持续增高,结直肠癌的疗效和预后都有显著改善。然而,结直肠癌的远隔转移仍然是结直肠癌治疗的难点和重点。本文回顾了结直肠癌远隔治疗的历史,总结了结直肠癌肝转移、肺转移、盆腔局部转移和腹膜转移的治疗策略和疗效。     

Long-term medical care of testicular cancer survivors

Testicular cancer is the most common solid tumor diagnosed in men 20 to 35 years of age. Because of highly effective treatments that may include surgery, chemotherapy, and radiation therapy, most patients become long-term survivors. Health-related issues that confront testicular cancer survivors include the late medical effects of chemotherapy, the late relapse of disease, the development of second cancers, the effect of the disease and treatment on fertility, and the psychosocial consequences. This case-based discussion focuses on the primary care physician's evaluation and management of a long-term survivor of testicular cancer who was previously treated with surgery and chemotherapy.     

Regional and systemic chemotherapy for advanced colorectal cancer

Progress in regional arterial infusion therapy for metastatic cancer confined to the liver from colorectal primary and in systemic chemotherapy for widespread disease has been limited. Despite considerable search for effective antitumor agents, only few drugs have been shown to have efficacy to warrant additional evaluation alone or in multidrug regimens. Despite high response rates reported with regional therapy and some of the systemic chemotherapy regimens, significant prolongation of the overall survival on these treatment programs remains to be documented. Although chemotherapy for advanced large bowel cancer is only moderately effective at present, patients do obtain substantial benefit occasionally. Thus, chemotherapy should be attempted and there should be trials of new treatment regimens to find effective treatments for these patients.     

Is there an optimal neoadjuvant therapy for locally advanced pancreatic cancer?

Treatment of locally advanced pancreatic cancer is challenging. Despite continuing research, effective treatments continue to be elusive with median survival of only 8-12 months. Treatment options for locally advanced pancreatic cancer include radiation therapy, concurrent chemoradiation or chemotherapy. It is felt that radiation therapy is a suboptimal treatment as most of patients will die of systemic disease. In the past, radiation with 5-FU was the standard treatment for locally advanced pancreatic cancer. But now radiation has been used with combination other chemo agents such as paclitaxel or gemcitabine in order to increase the efficacy. Chemotherapy such as gemcitabine alone or gemcitabine doublet also has been studied in patients with locally advanced pancreatic cancer as well with overall survival being approximately the same magnitude as chemoradiation. The exact role of chemoradiation or chemotherapy in treatment of locally advanced pancreatic cancer is yet to be defined. Hence, this review summarizes and compares of role of radiation, chemoradiation and chemotherapy in treating this disease.     

Progress in the treatment of pulmonary metastases after liver transplantation for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and is the third leading cause of cancer-related death. Liver transplantation (LT) has become a curative treatment for patients with HCC. However, recurrence and metastasis after LT are the main factors reducing long-term survival in patients, and the lung is the most common site of metastasis after LT for HCC, although metastasis to liver, para-aortic lymph nodes and renal periphery are observed. Thus, the treatment of pulmonary metastases after LT for HCC has become a hot research topic, the successful treatment of pulmonary metastases can significantly prolong the survival of LT patients. Although single conventional treatment (chemotherapy, surgery and external beam radiation therapy), immunosuppression, image-guided minimally invasive therapy (radiofrequency ablation, microwave ablation, cryoablation, and brachytherapy) and molecular targeted drugs have had a significant effect, patients do not have durable remission and the long-term survival rate is disappointing. Therefore, improving existing treatments and identifying a more effective combination therapy are important research issues in the prevention and treatment of pulmonary metastases after LT for HCC. The paper reviewed single conventional treatments, new treatments, and combination therapy, to provide a basis for the best treatment of these patients.     

Recent advances in multidisciplinary management of hepatocellular carcinoma

The incidence of hepatocellular carcinoma(HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinaryteam should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.     

人工肝和干细胞在肝衰竭治疗中的进展

目前肝衰竭的治疗手段主要包括内科综合治疗、人工肝支持系统治疗、肝移植和干细胞移植等,近些年人工肝支持系统和干细胞移植在肝衰竭治疗方面取得了较大的进展。介绍了临床上常用的非生物型人工肝治疗方法和生物型人工肝的细胞来源、细胞培养方式、生物反应器及临床应用等。探讨了干细胞治疗肝衰竭的机制和临床应用。针对人工肝和干细胞治疗肝衰竭临床疗效欠佳的问题,提出了两者联合治疗肝衰竭的可行性。     

Therapeutic strategies for hepatic metastasis of colorectal cancer: overview

To determine the treatment strategy for hepatic metastases of colorectal cancer, it is important to take into account whether metastases are still localized in the liver, or whether the tumor has metastasized throughout the body. For liver-limited metastasis, hepatectomy is the therapeutic strategy that offers the best prospect of improving a patient's prognosis if the case is deemed resectable. In cases when surgery is not indicated for hepatic metastases of colorectal cancer, chemotherapy is the first-choice treatment. Chemotherapy for colorectal cancer has made vast strides in recent years through advances such as the development of molecular targeted drugs. In cases where chemotherapy is effective and surgical resection becomes possible (conversion chemotherapy), the long-term prognosis may be good. The value of preoperative chemotherapy in resectable cases (neoadjuvant chemotherapy) has also been reported. The improvement in prognosis achieved by eradicating tiny latent metastases is important in conversion therapy, as well as in neoadjuvant chemotherapy. It will be important to achieve further improvements in the prognoses of patients with hepatic metastases of colorectal cancer through a combination of advances in diagnostic imaging, improvements in surgical techniques, and more effective chemotherapy treatments.     

Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency

Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.     

介入治疗在中晚期肝癌降期中的作用

介入治疗已成为中晚期肝癌姑息治疗的主力军。与此同时,在肝癌降期领域,介入治疗也发挥着越来越重要的作用,通过局部介入治疗可使中晚期肝癌的瘤灶体积减小、数量减小使之符合肝癌移植或者切除术标准。介入降期技术包括经肝动脉化疗栓塞术、药物缓释微球、经动脉放射性栓塞治疗以及各种消融治疗技术(射频消融、微波消融、冷冻消融、酒精消融)等。最佳的介入降期策略仍未达成共识,但是通过开展高级别循证医学研究,对不同方法的最佳可获益人群进行筛选,评估不同介入降期策略对后续肝移植手术在手术难度、安全性、术后疗效等方面的影响,有望提升介入治疗在中晚期肝癌降期的效果。     

Treatment of hepatocellular carcinoma

Hepatocellular carcinoma is one of the most common cancers worldwide. The incidence of this disease is also increasing in the Western world. Typically, HCC is diagnosed when patients have already reached an advanced stage of the disease and the prognosis is poor. Potentially curative treatment options include surgical resection or liver transplantation and can be offered to patients with adequate liver function and tumour stage. Other non-surgical treatment options such as radiofrequency ablation, cryoablation, ethanol or acetic acid injection, transarteriel chemoembolisation radiation therapy and systemic chemotherapy can be offered either alone or in combination to selected groups of patients. These treatments can improve (tumour-free) survival and in a few cases even cure the patient.