晚期结直肠癌化疗的研究现状

美国纽约大学癌症研究所血液和肿瘤教授．著名的胃肠道肿瘤专家Hochster教授近期在上海就结直肠癌的化疗及其进展等问题发表了演讲。并与国内肿瘤治疗领域的专家进行了近距离的讨论，现将Hochsler教授演讲内容和他与国内肿瘤化疗医生所进行的互动讨论作一概述。     

结直肠癌外科治疗的国内外新进展

随着科学技术的发展,结直肠癌的外科治疗手段和方法和取得了很大进展.本文就结直肠癌外科治疗新方法、新辅助治疗和靶向治疗近年来国内外进展综述如下.一、外科治疗手段的进展目前,结直肠癌外科治疗新方法包括经肛门内窥镜微创手术(transanal endoscopic microsurgery,TEM)、腹腔镜技术、达芬奇操作系统(da Vinci surgical system)、经自然孔道内镜外科技术(natural orifice transluminal endoscopic surgery,NOTES).     

单克隆抗体治疗晚期或转移性结直肠癌的进展

结直肠癌是我国最常见的恶性肿瘤之一。2008年卫生部肿瘤防止办公室发布的2006年我国恶性肿瘤发病率数据和十大恶性中路发病率最新排序,结直肠癌位列第4位。《2008年中国卫生统计年鉴》指出2004~2005年前十位恶性肿瘤死亡率（合计）中,结直肠癌死亡率上升到第5位,有7·25×10万死于结直肠癌[1]。目前对结直肠癌的治疗仍是以手术为主、辅以局部或全身放疗及化疗的综合治疗。靶向治疗使到转移性结直肠癌（mCRC）的治疗效果得到了进一步提高,成为一种新的治疗手段。现只就单克隆抗体治疗晚期或转移性结直肠癌的现状、最新的研究进展作一综述。     

结直肠癌肝转移的综合治疗

目的 总结和分析结直肠癌肝转移的早期诊断与治疗效果。方法 对19例结直肠癌肝转移患者通过检测血液癌胚抗原(CEA)、B超、CT扫描等检查．提出早期诊断及治疗方案。对肝转移灶根治切除的7例患者术后常规行肝动脉或门静脉插管皮下埋泵区域化疗术(DDS)．与12例仅行肝转移灶根治切除的患者进行1、3年生存率的比较。结果 早期诊断结直肠癌肝转移并到根治切除且术后行DDS的患者与单纯肝转移灶根治切除组1、3年生存率分别为86％、60％和66％、40％,统计学分析具有显著差异。结论 结直肠癌肝转移根治切除辅助术后行DDS治疗效果最好。     

结直肠癌综合治疗的规范化实施

结直肠癌目前位居全世界常见恶性肿瘤的第3位。我国结直肠癌发病率逐年上升,每年约有40万新发病例,目前在我国消化系统恶性肿瘤中列第2位。近年来多学科综合治疗成为结直肠癌的主要治疗模式,它以循证医学为基础,强调诊疗的规范化及个体化,为病人提供最佳的诊疗效果。目前,我国肿瘤专科仍面临着一些亟待解决的问题,需要一套强有力的规范化制度。应该依据病人的具体情况、癌肿特点、病理及生物学特性,根据病人经济情况有计划、合理的应用现有治疗手段,制定出一套符合我国病人人群特点的整体规范化治疗方案,以期提高治愈率和病人的生活质量。     

靶向治疗BRAFV600E突变型晚期结直肠癌28例疗效观察

为观察靶向治疗V-raf鼠肉瘤病毒癌基因同源体B(BRAF)V600E突变型晚期结直肠癌患者的疗效,将56例BRAFV600E突变型晚期结直肠癌患者随机分为对照组和观察组,每组28例。对照组患者采用BRAF抑制剂治疗,观察组患者采用BRAF抑制剂和西妥昔单抗治疗,观察2组患者的疗效、血清肿瘤标志物水平以及不良反应发生率。结果显示,观察组患者总有效率明显高于对照组(P <0.05);治疗前2组患者血清肿瘤标志物水平比较差异无统计学意义(P>0.05),治疗后观察组患者血清肿瘤标志物水平低于对照组(P <0.05);2组患者均无明显不良反应(P>0.05)。结果表明,对BRAFV600E突变型晚期结直肠癌患者行靶向治疗时,选择BRAF抑制剂和西妥昔单抗治疗,疗效显著,且安全性高。     

调整XELOX方案用法治疗老年晚期结直肠癌的疗效观察

为观察调整XELOX方案用法治疗老年晚期结直肠癌的疗效及安全性,本研究通过调整XELOX方案用法,对36例老年（年龄≥65岁）晚期结直肠癌患者进行化疗。具体化疗方案：卡培他滨每次1250mg／m2,2次／d,d1-7,d13-21,口服;奥沙利铂65mg／m2静脉滴注2h,d1,d15;28d为一周期。结果表明,36例患者中,部分缓解15例,疾病稳定11例,疾病进展10例,总有效率为41．7％（15／36）,临床获益率为72．2％（26／36）。中位疾病进展时间为7．1个月。主要不良反应为恶心呕吐、中性粒细胞和血小板减少、肝功能损害,多为I、Ⅱ度。结果表明,调整XELOX方案用法治疗老年晚期结直肠癌疗效好,不良反应发生率低,安全有效。     

结直肠癌肝转移的治疗进展

肝脏是结直肠癌转移的最常见器官，10％～25％的结直肠癌患者在确立诊断时即已存在肝转移，另有20％～25％的患者在肠癌术后发生肝转移，因此结直肠癌肝转移的发生率可高达50％，而能获得手术切除者仅占lO％～20％。近年来随着新的化疗药物的应用，局部介入治疗技术的发展，使一部分患者的肝癌缩小而获得二期切除。     

结直肠癌治疗的新概念--综合治疗的发展和展望

大肠癌作为实体瘤,最有效的治疗方法一直是以外科手术切除为主。但从外科手术治疗的历史来看,经一个世纪的努力,根治性切除后病人的5年生存率一直徘徊在50％左右,从范围较小的局部切除到广泛的淋巴清扫或多脏器联合切除的扩大根治术都未能达到令人满意的结果,究其原因,固然早期诊断、早期手术所占比例不高是一十分重要的原因,但即使在根治性切除后仍有较高的局部复发率和远处器官转移率,因此这种高达30％～50％的总发病率清楚地显示了手术治疗的能力有限。当前在直肠癌根治性切除手术中,直肠系膜全切除(total mesotectal excision,TME)操作虽然使局部复发率有了明显下降,普遍达到10％以下,但并     

高强度聚焦超声在结直肠癌肝转移治疗中的研究现状

肝脏是结直肠癌最常见也最重要的转移部位,而肝转移是结直肠癌治疗失败最重要的因素之一。手术切除治疗结直肠癌肝转移(CRLM)疗效确切,但手术切除率低且复发率高,化疗、放疗副作用较大,射频消融并发症较多,高温、冷冻等其他治疗效果均不理想。高强度聚焦超声(HIFU)是近年来发展迅速的实体肿瘤局部消融新技术,其不仅具有创伤小、并发症少、恢复快及肿瘤组织坏死确切等优点,还能在有效消融肿瘤病灶的同时保存和提高宿主抗肿瘤免疫能力。近年来,HIFU局部消融在临床治疗中的应用逐步深入,本文拟就其治疗结直肠癌肝转移的机制、现状作一简要综述,并探讨目前存在的问题,展望临床应用前景。     

New active drugs for the treatment of advanced colorectal cancer

Newer active drugs have been recently added to the pharmacological armamentarium for the treatment of metastatic colorectal cancer. Aflibercept, a recombinant fusion protein composed of the extracellular domains of human vascular endothelial growth factor receptors (VEGFR) 1 and 2 and the Fc portion of human immunoglobulin G1 (IgG1), is an attractive second-line option in combination with folfiri for patients who have failed folfox +/- bevacizumab. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGFR-2, provided similar results in the same setting. Tas-102, an oral fluoropyrimidine, and regorafenib, a multi-tyrosine kinase inhibitor, are both able to control the disease in a considerable proportion of patients when all other available treatments have failed. These new therapeutic options along with the emerging concept that previous therapies may also be reitroduced or rechallenged after regorafenib and Tas-102 failure are bringing new hope for thousands of patients and their families.     

Surviving colorectal cancer

About a quarter of a million people in the UK are living with a diagnosis of colorectal cancer. As more patients are being diagnosed and subsequently cured, the demands on currently available follow-up services will increase. We know that cure can come at the cost of bowel, urinary, neurological and sexual problems - most of these issues are underestimated, poorly understood and inadequately managed by clinicians. At this point in time follow-up services neither meet patients’ needs for rehabilitation and support, nor are they the most cost-effective way to pick up treatable recurrence. As part of the survivorship program the diagnosis of cancer can also be an important opportunity to stimulate lifestyle changes to help reduce recurrence rates and improve quality of life. There is now a shift in management of these people with a greater focus on recovery, health and well-being after cancer treatment. Through the National Cancer Survivorship Initiative (NCSI) a model of change addressing these issues has been outlined.     

Nonresectional palliative abdominal surgery for patients with advanced colorectal cancer

Objective Nonresectional palliative abdominal surgery (e.g. defunctioning stoma/bypass) may be appropriate for patients unsuitable for curative resection, to deal with complications of advanced colorectal malignancy such as obstruction. Our aim was to review the outcome of surgery in these patients within our institution. Method All patients undergoing palliative surgery without resection for colorectal carcinoma between July 1998 and January 2007 were identified from our prospectively compiled colorectal cancer database. Data were extracted related to patients’ demographics, presentation, tumour site, operative intervention, complications, oncological therapies, length of hospital stay and postoperative survival. Results One hundred and ninety‐three patients were identified with a median age of 79 years (31–94 years). Fifty per cent were operated on an emergent basis for obstruction or perforation, and 50% on an elective basis. One hundred and sixty‐nine patients had defunctioning stomas formed of which 156 were loop stomas. Twenty‐four patients underwent bypass procedures. Thirty‐day mortality rate was 13.5% and postoperative morbidity rate 47%. Median survival was 247 days, with 1‐year survival of 38%. Patients undergoing operation on an emergent basis had poorer long‐term survival (127 vs 320 days, P = 0.002). Conclusion Nonresectional palliative abdominal surgery is associated with relatively high morbidity and mortality, particularly when performed in the emergency setting. However, in this patient group with a very poor outlook, it may be offered with reasonable survival expectations.     

80岁以上高龄结直肠癌外科治疗临床探讨

目的探讨80岁以上高龄结直肠癌的临床特点及外科治疗方法。方法收集我院2001年1月至2009年6月诊治的85例80岁以上高龄结直肠癌患者临床资料,分析其临床及诊治特点、术后并发症及预后。结果手术率94.12%,根治率80%,术后并发症发生率21.25%,手术死亡率1.25%;1、3、5年生存率分别为61.1%、57.5%、37.5%;52.5%死于肠癌,47.5%死于他病。结论年龄并非高龄结直肠癌患者的手术禁忌,只要加强围手术期处理,可取得较好的近期效果,但远期疗效并不理想。     

用多学科团队模式推动结直肠癌的规范化治疗

由于结直肠癌的新发病例数不断上升和结直肠癌治疗的复杂性不断增加,结肠癌的规范化诊疗显得尤为重要,多学科团队(multidisciplinary team,MDT)的诊疗模式可以使临床诊断更加准确,促进建立合理的治疗流程,促进不同学科专家更好地进行沟通和信息共享,并监督结直肠癌病人治疗的连贯性,保证治疗方案如期实施;而且能提高医院效率及质量,降低医院费用及成本,减少浪费;为年轻医生提供学习的机会。用 MDT 模式推动结直肠癌规范化诊治,能够给病人带来更多获益。     

高龄大肠癌术后并发症防治体会(附86例报告)

目的 总结高龄大肠癌患者术后并发症防治的经验。方法回顾性分析手术治疗的86例70岁以上老年人大肠癌病例资料。结果所有患者均行手术治疗（13例因并发结直肠梗阻而行急症手术）,其中64例（73．3％）属根治性切除（D3）,13例肿瘤姑息性切除,6例仅永久性结肠造口术．3例剖腹探查加肿瘤种植结节或转移淋巴结活检术。总切除率为89．5％。无手术死亡病例。15例发生并发症共21例次,占17．4％,其中肺部感染7例、切口感染7例、切Ⅵ裂开3例、尿潴留1例,心力衰竭2例、脑血管意外1例等,无吻合口瘘。本组获得随访77例,其中1年生存率是85．7％（66／77）,3年生存率70％（54／77）5年生存率41．5％（32／77）。结论做好高龄大肠癌的术前准备（包括内科伴发病的处理）,正确掌握不同术式的适应证和手术操作以及术后处理,可有效提高手术成功率,降低死亡率和术后并发症的发生。     

Prognostic significance of lymphovascular or perineural invasion in patients with locally advanced colorectal cancer

Background

This study was designed to evaluate the prognostic significance of the positivity of lymphovascular (LVI) and perineural invasion (PNI) in patients with locally advanced colorectal cancer.

Methods

From January 1999 to December 2009, 1,437 consecutive patients who underwent curative surgery for stage II or III colorectal cancer were analyzed. Patients were then categorized into 4 groups: LVI−/PNI− (n = 850), LVI+ only (n = 178), PNI+ only (n = 271), and LVI+/PNI+ (n = 138).

Results

With a median follow-up period of 56 months, the 5-year overall survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 82%, 73%, 71%, and 56%, respectively (P < .001), and the 5-year disease-free survival rates of patients with LVI−/PNI−, LVI+ only, PNI+ only, and LVI+/PNI+ were 80%, 70%, 65%, and 46%, respectively (P < .001). In multivariate analysis, LVI+/PNI+ was an independent prognostic factor for both overall survival (P < .001) and disease-free survival (P < .001).

Conclusions

Positivity of both LVI and PNI is a strong predictor of overall and disease-free survival in patients with stages II and III colorectal cancer.     

综合治疗时代晚期肝癌治疗的全局观

晚期肝癌严重威胁我国人民的生命和健康.肝脏的解剖结构及生理功能决定了肝癌具有天然的化疗耐药的特点.目前已有多种靶向治疗药物获批用于晚期肝癌的一线和二线治疗.免疫治疗的出现使肝癌的治疗进入新的时代.靶向与免疫治疗药物在机制上具有协同作用,而且二者的联合使用已在临床上使更多的晚期肝癌病人获益.同时,在靶向联合免疫的全身治疗...     

老年人结直肠癌的外科治疗（附98例分析）

目的探讨老年结直肠癌患者的外科治疗情况。方法回顾性分析98例经外科治疗的60岁以上结直肠癌患者的临床资料。结果老年结直肠癌患者入院前误诊率为52%,并存病为57.2%,手术切除率为92%,术后并发症发生率为32.6%,围手术期死亡率3%。结论手术切除是老年结直肠癌患者最好治疗方法,但早期诊断,合理处理并存病,选择适当的手术方式,积极预防和治疗并发症是外科手术治疗成功的关键。