结直肠癌腹膜转移的治疗

全球结直肠癌发病率逐年增加,对于无远处播散的患者,手术切除原发肿瘤和区域淋巴结清扫是唯一可能治愈的方法。但一些患者仍会出现肝脏、肺和腹膜等部位转移。全身化疗联合肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）应作为腹膜转移癌的标准治疗,是迄今治疗效果最好的方案。本文将对结直肠腹膜转移的发病现状、机制、特点及诊疗进展进行综述。      

结直肠癌伴腹膜转移治疗的研究进展

结直肠癌是全球第三大常见癌症，也是与癌症相关死亡的第四大常见原因。转移性疾病仍然是结直肠癌死亡的主要原因，除了淋巴和血源传播途径外，结直肠癌还会引起肿瘤细胞的腹腔传播，最终导致腹膜癌。随着各种治疗的进展，转移性结直肠癌患者的预后明显改善，但对伴有腹膜转移的患者疗效并不理想。最近越来越多的研究表明，肿瘤细胞减灭术(CRS)和腹腔热灌注化疗(HIPEC)可使结直肠癌伴腹膜转移患者受益，预后较好，腹腔内加压气溶胶化疗(PIPAC)、新辅助化疗、Radspherin短距离辐射等新型疗法也相继出现。本文就结直肠癌伴腹膜转移的治疗研究进展作一综述。     

结直肠癌腹膜转移的多学科综合治疗

腹膜转移是结直肠癌常见转移部位之一,传统观念认为其预后差,没有手术治疗的价值。近年来,随着外科技术、精确控温的腹腔热灌注化疗以及多学科综合治疗的进步,对结直肠癌腹膜转移的认识和治疗策略发生很大的变化,拟就这一问题进行综述。在预后方面,如果仅行姑息性化疗,结直肠癌腹膜转移的预后差于肝、肺等非腹膜部位的转移;但对于一部分合适的患者施行完全性腹膜减瘤术联合腹腔热灌注化疗,则可能使部分患者获得长期生存;腹膜转移癌的预后因素包括腹膜播散癌指数、减瘤术完全性程度、是否合并腹膜外转移(肝脏等)、腹膜表面疾病严重程度评分和日本腹膜分期等。在治疗方面,完全性腹膜减瘤术联合腹腔热灌注化疗以及全身治疗(化疗+靶向治疗),可能是最佳的多学科综合治疗策略。     

结直肠癌腹膜转移治疗的临床研究进展

腹膜是结直肠癌转移的第三常见部位。结直肠癌腹膜转移通常被认为是终末期疾病,预后差。随着系统性药物治疗的进展,转移性结直肠癌患者预后明显改善,但腹膜转移患者生存获益仍然较少。腹膜肿瘤细胞减灭术和腹腔热灌注化疗能够显著改善腹膜转移患者的预后。新型治疗方法如腹腔加压气溶胶化疗、腹腔MOC31PE抗毒素治疗等也随之出现。本文将对结直肠癌腹膜转移治疗的临床研究进行综述。     

结直肠癌腹膜转移伴卵巢转移的治疗现状与挑战

腹膜是结直肠癌转移的好发部位。出现腹膜转移的女性结直肠癌患者常伴有卵巢转移。通常认为出现腹膜转移和卵巢转移的女性结直肠癌进展迅速且预后极差,目前仍无有效的治疗手段。虽然结直肠癌患者接受化疗及靶向药物后可显著改善预后,但同时伴有腹膜转移和卵巢转移的女性结直肠癌患者却无法明显获益。许多研究证实肿瘤细胞减灭术（CRS） 联合腹腔内热灌注化疗（HIPEC）可延长这类患者的生存期,改善生活质量。本文综述了结直肠癌腹膜转移和卵巢转移患者的诊治现状和相关进展。     

腹腔微环境与结直肠癌腹膜转移关系的研究进展

腹膜转移是结直肠癌（colorectal cancer,CRC）常见的转移方式之一,通常预示着患者不良的预后。腹膜衬贴于腹盆壁内面和腹盆腔各脏器的表面,具有丰富的血液供应和大量常驻和迁移到此处的特定类型的细胞。腹腔中的多种细胞成分,细胞外基质以及局部特殊的理化性质共同构成了一个复杂和相对稳定的腹腔微环境;多种细胞在此环境中可以被结直肠癌细胞所诱导,参与并为肿瘤的生长、侵袭和腹膜转移提供适宜的“土壤”。本文就这些腹腔中参与构成腹腔微环境的主要细胞成分进行综述。      

腹腔热灌注化疗治疗结直肠癌腹膜癌

结直肠癌局域性进展可形成腹膜癌，大约10％的患者初诊即发现腹膜癌，有4％～19％的患者在根治术后随访期发生腹膜癌，25％～35％的复发患者以腹膜癌为唯一表现。全身化疗对此类腹膜癌只是姑息性治疗，中位生存期不足6个月。缩瘤术加腹腔热灌注化疗则可清除宏观和微观癌细胞。荷兰癌症中心的Ⅰ、Ⅱ、Ⅲ期临床试验总结分析表明，接受完全缩瘤术加腹腔热灌注化疗者的中位生存期可达42．9个月，1、3、5年生存率分别是95％、56％和43％，明显高于传统治疗方法，已成为英国、法国、意大利、荷兰、西班牙和澳大利亚等国的标准治疗。     

结直肠癌腹膜种植转移的相关因素分析

  目的   探讨影响结直肠癌腹膜种植转移的临床病理相关因素。   方法   收集2005年1月至2009年12月广西医科大学第一附属医院的结直肠癌患者1 170例的临床病理资料, 研究结直肠癌腹膜种植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, 并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   1 170例结直肠癌患者中, 腹膜种植转移92例(7.86%)。单因素分析显示, 患者的年龄、肿瘤部位、浸润肠腔周径、肿瘤最大径、组织病理学类型、分化程度、肠壁浸润深度、淋巴结转移和血CEA水平与结直肠癌腹膜转移有关。Logistic多因素分析显示, 肿瘤部位、浸润肠腔周径、分化程度、肠壁浸润深度、淋巴结转移和血CEA水平与结直肠癌腹膜转移的有关。   结论   肿瘤部位、浸润肠腔周径、分化程度、肠壁浸润深度、淋巴结转移和血CEA水平是结直肠癌发生腹膜转移的独立相关因素。      

结直肠癌腹膜转移的治疗: 新事实、新知识和新未来

腹膜转移是结直肠癌的常见转移方式,即使进行积极治疗,结直肠癌腹膜转移患者的预后仍较差。近年来,腹腔加压气溶胶化疗（pressurized intraperitoneal aerosol chemotherapy,PIPAC）作为一种新的腹腔内化疗方式受到了广泛关注,全球多个国家的研究者开展了大量与PIPAC相关的前瞻性研究和临床试验,对于腹膜癌患者来说,PIPAC已成为一种安全有效的且有前景的治疗方式,多个医疗中心已经将其用于治疗腹膜癌患者。随着PIPAC相关的临床证据越来越多,其在临床中的应用越发受到重视。本文就PIPAC治疗结直肠癌腹膜转移的理论基础、发展历程、操作流程、适应证、禁忌证、药物方案和临床应用的最新进展进行综述,以期为临床实践和研究提供参考。     

Experimental radioimmunotherapy of small peritoneal metastases of colorectal origin

Radioimmunotherapy using radiolabeled monoclonal antibodies (MoAbs) directed against tumor-associated antigens might be an effective treatment modality for small volume disease. Our aim was to optimize an experimental model of radioimmunotherapy for small peritoneal metastases of colorectal origin using the anti-CEA MoAb MN-14. In nude mice with intraperitoneal (i.p.) LS174T tumors, a protein dose-escalation study was carried out to determine the maximal dose of radioiodinated MN-14 to be used in radioimmunotherapy. The biodistribution of radioiodinated MN-14 was determined after intravenous (i.v.) and i.p. administration. Finally, the therapeutic efficacy of escalating activity doses of (131)I-labeled MN-14 (62.5-500 microCi) was assessed and compared to that of unlabeled MN-14 or 500 microCi of (131)I-labeled irrelevant control antibody. At protein doses higher than 25 microg, uptake in tumor was reduced, presumably due to saturation of tumor antigen. During the first 24 hours i.p. administration led to higher tumor uptake and higher tumor:blood ratios than i.v. administration. Median survival of the control groups was 38 days (unlabeled MN-14) and 52 days ((131)I-labeled nonspecific antibody). Median survival of the groups treated with increasing activity doses of (131)I-labeled MN-14 was 42 days (62.5 microCi), 49 days (125 microCi), 63 days (250 microCi) and 101 days (500 microCi), respectively (p < 0.0001 compared to unlabeled MN-14). The present study shows that the anti-CEA-antibody MN-14 preferentially accumulates in i.p. LS174T tumor xenografts after both i.p. and i.v. administration. Intraperitoneal radioimmunotherapy using (131)I-labeled MN-14 delays significantly the outgrowth of peritoneal LS174T metastases, even at relatively low activity doses.     

结直肠癌腹膜转移的治疗:新事实、新知识和新未来

结直肠癌腹膜转移（colorectal cancer peritoneal metastasis,CRCPM）一直是荷兰临床肿瘤学研究的重点领域之一,对比系统化疗加姑息手术治疗,CRCPM患者更易从肿瘤细胞减灭术（cytoreductive surgery,CRS）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）中获益,CRS+HIPEC在治疗CRCPM中已具有稳定的临床基础。目前,荷兰建立了全国肿瘤登记处,对所有腹膜癌病例进行详细登记和分析。本文重点介绍了荷兰CRCPM最新研究,包括流行病学研究、多中心随机临床试验、基础和转化研究的新成果,给出了国际热点问题和学术争鸣的荷兰答案,提出了腹膜肿瘤学未来发展的新机遇和新方向。      

Update on clinical trials in colorectal cancer peritoneal metastasis

Abstract

Background/purpose: Peritoneal metastases (PM) arising from colorectal cancer (CRC) can be treated using cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in select patients.

Objective: To review clinical trials that were reported during the 10th International Congress on Peritoneal Surface Malignancies and dedicated to the treatment of CRC-PM.

Methods: Ten clinical trials were presented at the 10th Peritoneal Surface Oncology Group International (PSOGI) meeting in November 2016 in Washington DC. The flow charts of the studies were identified on ClinicalTrials.gov. Additional data were collected regarding the author’s presentations during the meeting.

Results: Four trials (Dutch, French, Italian and Spanish) focussed on a preventive strategy to decrease the rate of CRC-PM. Inclusions were closed for the French study – ProphyloCHIP. Two trials were specific, with one American study dedicated to appendix cancer and one French study testing phase 1 intraperitoneal oxaliplatin drug administration. CRS and HIPEC for PM were compared in others trials with different intraperitoneal treatments without hyperthermia or with no intraperitoneal treatment or with intravenous chemotherapy. Inclusions were closed for the French study – PRODIGE 7.

Conclusion: The number of recruiting trials evaluating CRS and HIPEC in the prevention or therapy of CRC PM is increasing, and these have been activated in the US and different European countries. It could be postulated that in less than a decade, clinical results will change the common practice and validate the impact of PSOGI on cancer treatment.     

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。     

Treatment and prevention of peritoneal carcinomatosis from colorectal cancer

PC from colorectal cancer is a terminal illness for which intravenous chemotherapy is the current standard treatment. However, a recent Dutch randomized study established the efficacy of maximal cytoreductive surgery plus IPCH to achieve statistically significant prolonged survival of these patients. In the near future, improvements of IPCH techniques and progress in selecting patients by radiologic imaging, by molecular biologic studies or further refinement of quantitative prognostic indicators will permit better results. Prospective studies must be conducted in the prevention of carcinomatosis in well-defined high-risk patients.