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。     

结直肠癌卵巢转移组织中CDX-2与CK7和CK20的表达及其临床意义

目的:探讨结直肠癌卵巢转移组织中CDX-2与CK7和CK20的表达及其临床意义,为结直肠癌卵巢转移的诊断和治疗提供理论依据.方法:回顾性分析结直肠癌卵巢转移患者54例临床病理资料.采用免疫组织化学(SP法)检测和分析20例原发卵巢癌及结直肠癌卵巢转移患者癌组织中CDX-2、CK7和CK20的表达.对临床病理特征进行单因素及多因素分析.结果:CDX-2,CK7和CK20在原发性卵巢癌组织中的阳性表达率分别为0(0/20),95％ (19/20),15％ (3/20),在结直肠癌卵巢转移组织中的阳性表达率分别为100％(20/20),10％(2/20),90％ (18/20),差异有统计学意义(P ＜0.05);Cox回归模型多因素分析结果显示:卵巢包块大小、转移发生时间、腹膜种植转移、卵巢转移灶是否切除、是否化疗是影响结直肠癌卵巢转移患者预后的独立危险因素(P＜0.05).卵巢包块大、卵巢转移灶未切除、同时性卵巢转移、伴有腹膜转移、未行化疗的结直肠癌卵巢转移患者生存期短,预后差.结论:通过检测原发卵巢癌及结直肠癌卵巢转移组织中CDX-2、CK7和CK20的表达,有助于鉴别诊断原发卵巢癌与结直肠癌卵巢转移;尽量创造卵巢转移灶切除的机会可能有助于提高结直肠癌卵巢转移患者生存期.     

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。      

细胞减灭术联合腹腔热灌注化疗治疗结直肠癌腹膜转移的临床应用与展望

结直肠癌为我国常见恶性肿瘤之一, 其发病率逐年上升。腹膜为结直肠癌第2常见转移部位, 早期诊断困难, 预后不良。既往多采取全身性系统静脉化疗作为腹膜转移的主要治疗策略, 其全身不良反应明显, 且不能有效控制肿瘤进展。近年来, 外科技术、理念、设备的不断发展以及新的化疗药物与靶向药物的出现改善了结直肠癌腹膜转移患者的生存质量及预后。细胞减灭术(CRS)联合腹腔热灌注化疗(HIPEC)可在有效清除腹腔内游离癌细胞与亚临床病灶的同时, 减轻化疗药物带来的全身不良反应, 最大程度上实现宏观与微观的肿瘤根治, 目前, CRS+HIPEC已被国内外作为结直肠癌腹膜转移的一线治疗方案。文章分析总结了CRS+HIPEC治疗结直肠癌腹膜转移的生存疗效、预后因素分析、化疗安全性等问题, 探讨了HIPEC治疗目前存在的问题与争议。     

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。     

西妥昔单抗联合FOLFIRI方案及腹腔灌注治疗结直肠癌腹膜转移一例

结直肠癌在全球男性常见恶性肿瘤中占第四位,女性中占第三位,其发病率呈逐年上升趋势。腹膜转移是仅次于肝、肺转移的最常见部位之一。。尸检时发现结直肠癌腹膜转移的发生率高达40%。因常引起肠梗阻或者腹腔积液,严重影响患者的生活质量,其预后较其他部位转移的患者更差。在使用了氟尿嘧啶为基础的全身化疗药后,此类患者的中位生存期仅为5.2～7个月。随着一些新的化疗药物（如：奥沙利铂和伊立替康）和分子靶向药物（如：西妥昔单抗和贝伐珠单抗）,以及外科减瘤术联合腹腔内热灌注化疗（hyperther-mic intraperitoneal chemoperfusion, HIPEC ）的联合应用，此类患者的生存期有了很大程度的延长。     

结直肠癌卵巢转移的临床特征及诊治策略

结直肠癌卵巢转移属少见转移类型,发病率低,在影像学上与原发性卵巢癌无法区分。因其极易被漏诊或误诊、对全身化疗反应差、无标准治疗手段等原因,结直肠癌卵巢转移患者的预后不容乐观。该文综述了结直肠癌卵巢转移的临床特征和诊治策略,以期为临床实践提供参考。     

结直肠癌卵巢转移的外科治疗及预后分析

目的探讨结直肠癌卵巢转移的外科治疗及影响患者预后的因素。方法搜集67例结直肠癌卵巢转移患者的资料,预后影响因素的单因素分析采用Log rank检验,多因素分析应用Cox比例风险模型进行回归分析。结果单侧卵巢转移、单纯卵巢转移、肿瘤转移仅限于盆腔内者多行根治性切除。全组67例结直肠癌卵巢转移患者总的1、3、5年生存率分别为71.0%、18.7%和9.2%。单因素分析结果显示,单纯卵巢转移、转移灶局限于盆腔内、单侧或双侧转移、手术方式是影响结直肠癌卵巢转移患者预后的主要因素(P<0.05)。多因素分析结果显示,仅手术方式是结直肠癌卵巢转移患者预后的独立影响因素(OR=3.531,P<0.001)。结论结直肠癌卵巢转移应行积极的外科治疗,争取根治性切除,有助于延长患者的生存时间。     

58例晚期卵巢癌患者发生腹腔内转移后的临床特征、疗效及预后影响因素分析

目的 探讨晚期卵巢癌患者发生腹腔转移后的临床特点、疗效,并探讨预后的影响因素。方法 回顾性分析湖北省天门市第一人民医院肿瘤科3个病区2013年1月—2016年1月期间病理诊断明确、初诊且临床资料齐全的65例晚期卵巢癌患者,其中发生腹腔转移的58例,对58例患者预后影响因素进行单因素和多因素生存分析。结果 58例诊断卵巢癌腹腔转移患者的平均年龄为(49.2±6.5)岁,从确诊卵巢癌到发生腹腔转移的平均时间为11个月,卵巢癌腹腔转移患者的中位生存时间为8周,而7例未发生腹腔转移者的中位生存时间为15周。单因素生存曲线比较显示,患者婚姻状况、生育史、哺乳史、恶性腹水、新辅助化疗、综合治疗(化疗+开腹的肿瘤细胞减灭术+腹腔热灌注化疗)、腹腔转移瘤数目、残余病灶大小、患者的生存质量(卡氏评分)、血浆中D-二聚体水平、尿液中微量白蛋白的水平与患者的预后均有关(P＜0.05)。Cox多因素回归模型分析显示,患者生育史、综合治疗、血浆中D-二聚体的水平、尿液中微量白蛋白水平为影响患者预后的独立危险因素(P＜0.05)。结论 晚期卵巢癌腹腔转移患者生存时间短,预后差;新辅助化疗联合肿瘤细胞减灭术及术后腹腔热灌注化疗,短期疗效好,既能提高晚期卵巢癌治疗有效性,又可改善晚期患者的生存质量;治疗前血浆中D-二聚体水平以及尿液中微量白蛋白持续维持在高水平或者不降低的患者,治疗效果差,预后也差,提示二者可以作为一种新的判断预后的指标。     

Early Start of Chemotherapy after Resection of Brain Metastasis from Colon Cancer with Synchronous Multiple Liver Metastases

Brain metastasis (BM) is infrequent in colorectal cancer (CRC) patients. Although BM from CRC is a late-stage phenomenon with an extremely poor prognosis, some subsets of patients would benefit from a multidisciplinary management strategy. The prognosis of patients with BM from CRC is associated with the curability of the therapy for BM and number of metastatic organs. The start of chemotherapy treatment usually requires a delay of about 4 weeks after surgical resection in patients with primary CRC having synchronous distant metastasis. However, there is no evidence to indicate the required length of this delay interval. In addition, there is a chance that a patient may die because postoperative chemotherapy was not started soon enough and a metastatic tumor was able to develop rapidly. Here, we present a case where combination chemotherapy with capecitabine and oxaliplatin (XELOX) was started within 1 week after resection of BM from colon cancer for synchronous multiple liver metastases. To our knowledge, this is the first report of the start of chemotherapy, involving treatments such as folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and XELOX within 1 week after resection of BM from colon cancer with synchronous multiple liver metastases. These findings suggest possible changes in the start time of chemotherapy after surgery in the future.Key Words: Colorectal cancer, Chemotherapy, Brain metastasis, Surgery, XELOX     

"When and how are peritoneal metastases of colo-rectal origin treatable"

Peritoneal metastasis (PM) of colorectal cancer (CRC) origin can be treated and cured. This article presents a practical guide for CRC surgeons facing a patient with PM and presents the different options of treatment at expert centers on peritoneal surface malignancies.The unexpected finding of PM could be overwhelming, especially during an emergency CRC surgery. Clear indications on managing these situations call for clarification to avoid any negative impact on the oncologic outcome of patients with CRC.All patients with PM of CRC origin must be evaluated by a tumor board or multidisciplinary team specialized in the management of peritoneal surface malignancies since currently there are available options of treatment for patients with resectable peritoneal disease, unresectable peritoneal disease, and even patients with synchronous liver metastases (LM) could benefit from a multimodal approach.     

122例结直肠癌卵巢转移患者的临床病理特征及预后

目的探讨结直肠癌卵巢转移患者的临床病理特征和预后。方法回顾性分析2010—2015年中国医学科学院肿瘤医院收治的122例结直肠癌卵巢转移患者的临床病理资料,生存分析采用Kaplan-Maier法,预后影响因素分析采用Log rank检验和Cox比例风险模型。结果122例结直肠癌卵巢转移患者的中位总生存时间(OS)为19.7个月,1、3、5年生存率分别为72.1%、24.7%和9.9%。122例患者中,行卵巢切除99例(81.1%)。行卵巢切除患者的中位OS(21.9个月)高于未行卵巢切除的患者(10.3个月,P<0.01)。单纯卵巢转移、原发肿瘤切除和卵巢转移灶切除均与患者的总生存有关(均P<0.01);原发肿瘤切除和卵巢转移灶切除为影响患者总生存的独立因素(均P<0.01)。结论结直肠癌卵巢转移患者接受积极的手术治疗,包括原发肿瘤切除术和卵巢转移灶切除术,可能获得生存改善。     

结直肠癌脑转移的临床特点和预后

目的 探讨结直肠癌脑转移的临床特点及预后.方法 筛选1 714例结直肠癌患者中脑转移病例36例,对其临床资料进行回顾性分析.结果 结直肠癌患者中脑转移2.1％ (36/1 714),占同期脑转移病例的3.3％.患者多为男性(21/36,58.3％)、直肠癌(19/36,52.8％)和诊断时分期为Ⅲ和Ⅳ期者(32/36,88.9％).其中分期是无脑转移生存的独立预后因素(HR=2.072,P=0.042).单发脑转移占55.6％(20/36).94.4％(34/36)的患者在发生脑转移的同时伴有颅外转移,其中肺是最常见的伴随转移器官(22/36,61.1％).递归分级分析(recursive partitioning analysis,RPA)分级为Ⅰ、Ⅱ和Ⅲ级患者的中位脑转移后生存时间分别为未达到、17个月和3个月(P=0.002).多因素分析显示,脑转移时患者的卡氏(Karnofsky performance status,KPS)评分是脑转移后生存的独立预后因素(HR=8.797,P=0.044),而放化疗未发现可改善脑转移患者的预后.结论 结直肠癌脑转移发生率较低,RPA是评估患者预后的重要指标,脑转移后放化疗未改善患者的预后.     

上皮性卵巢癌脑转移的现状分析

脑部是上皮性卵巢癌转移的少见部位, 但近20年来发生率有所提高。多数患者以头痛症状就诊, 诊断依赖于CT或MRI影像学检查。目前尚无一个统一的治疗规范, 采取手术和放化疗在内的综合治疗可以使患者受益。特别对于单发脑转移灶者, 以手术为主的综合治疗可以改善患者预后。立体定向放疗的应用为该治疗提供了新的前景。该病的预后差, 相关预后因素尚有争议, 目前一致认为患者一般情况良好和未合并颅外病灶有利于预后。      

晚期肺癌肝转移的综合治疗进展

肝脏是肺癌血液转移常见的部位。存在肝转移患者病情迅速发展，多在7个月内死亡。因此，采取积极有效的治疗措施，对进一步改善晚期肺癌患者的预后有极其重要的意义。目前，针对肺癌肝转移的治疗还没有达成统一的治疗计划，常见的治疗方法有手术治疗、全身化疗、介入治疗、射频消融治疗、立体定向放疗、靶向治疗、免疫治疗等。对此，我们就近年来肺癌肝转移的综合治疗进展作一综述。     

Diagnostic Nodes of Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Among Colorectal Cancer Patients: A Swiss National Multicenter Survey

BackgroundThe management of patients with colorectal cancer (CRC) with peritoneal metastases is challenging, and the roles of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are unclear and debated among experts.Materials and MethodsThe experts of the Swiss Peritoneal Cancer Group were contacted and agreed to participate in this analysis. Experts from 9 centers in Switzerland provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Their responses were converted into decision trees on the basis of objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies.ResultsThe final treatment algorithms included a total of 5 decision criteria (age, Peritoneal Cancer Index [PCI], extraperitoneal metastases, Peritoneal Surface Disease Severity Score, and various risk factors [RF]) and 2 treatment options (HIPEC, yes or no). HIPEC was never recommended for patients without peritoneal metastases in the absence of RF for peritoneal metastases. For patients with a PCI ≤15 without organ metastases, all centers recommended CRS/HIPEC. There was also a consensus not to perform CRS/HIPEC in elderly patients (80 years and older), those with a PCI >20, and those with unresectable metastases. For patients with a PCI = 16 to 20, there was no consensus.ConclusionMultiple decision criteria relevant to all participating centers were identified. Because patient selection for CRS/HIPEC remains difficult, uniform criteria for the term “high risk” for peritoneal metastases and systemic metastases are helpful. Future trials and guidelines should take these criteria into account.     

Analysis of Prognosis of 122 Colorectal Cancer Patients with Concurrent Liver Metastasis

OBJECTIVE To explore prognostic factors and treatment choices for colorectal cancer (CRC) patients with concurrent liver metastases (CLM).METHODS The data of the 122 CRC patients with CLM, who were treated in our hospital from January 2000 to December 2005, were collected. Overall survival rate of the patients in our group was analyzed using Kaplan-Meier method, and the univariate and multivariate analyses of the 18 factors affecting the survival rate, including clinicopathologic factors and treatment methods, were conducted using Log-rank test and Cox regression model (SPSS13.0).RESULTS The median survival time of the 122 patients with CRC was 13 months. The 1, 2, 3 and 5-year survival rate was 52.46%, 24.59% , 12.30% and 3.28% , respectively. Univariate analysis combined with Kaplan-Meier curve revealed that the factors of prognosis included the size of the primary tumor, the levels of differentiation, lymphatic status, cancerous ileus (CI), the number, size and distribution of liver metastases, extrahepatic involvement, the serum CEA level at diagnosis, treatment modality, the extent of primary resection, chemotherapeutic modality and regimen. Multivariate analysis showed that CI,differentiation levels, serum CEA value at diagnosis and treatment modality were the independent prognostic factors of CRC patients with CLM.CONCLUSION For the CRC patients with CLM, poor differentiation of the tumor and CI, as well as a high CEA level indicate an unfavorable prognosis. Treatment choice is of special significance in treating the CRC patients with CLM, so active radical excision of the primary tumor and liver metastasis is strongly recommended in the CRC patients with hepatic metastasis alone. Interventional chemotherapy has advantages compared with the whole-body chemotherapy via peripheral vein, and the regimen of systemic chemotherapy containing oxaliplatin is preferred.