炎症性肠病的癌变预防及氨基水杨酸类制剂的潜在化学预防作用

虽然炎症性肠病(IBD)最终发展为结直肠癌的概率较低,但IBD相关性结直肠癌一直被认为是最令人担忧的并发症.近年来,该领域进展颇多,如确定了癌变的危险因素,癌症预防相关研究的证据日益增多.目前认为IBD发展为结直肠癌的最大危险因素是疾病持续时间,成功的预防策略应包括对这些远期结局进行早期干预.本文旨在综述该领域的最新进展,包括IBD相关性结直肠癌的流行病学特征、发病机制和化学预防,特别强调5-氨基水杨酸盐(5-ASA)疗法.     

炎症性肠病发病机制及治疗的研究进展

炎症性肠病(IBD)是一种肠道的特发性、慢性和复发性炎性疾病,其发病机制非常复杂,受到遗传、环境和微生物因素之间相互作用的影响,目前生物制剂治疗存在诸多缺陷。结直肠慢性炎性反应是结直肠癌发生发展的关键因素,IBD与结直肠癌高度相关,早期防治IBD对于预防癌变具有重要意义。     

炎症性肠病病人一级亲属结直肠癌发病率：一项人群基础队列研究[英]／Askling J…∥Lancet

炎症性肠病(IBD)病因不明，已明确遗传易感性在该病发病机制中起重要作用，鉴于IBD还是结直肠癌发生的重要风险因素，因此，IBD病人亲属也可能有遗传发生结直肠癌高风险。本研究的目的旨在评估．IBD病人一级亲属结直肠癌发病率，并研究IBD与结直肠癌发生之间的关系。     

炎症性肠病癌变的研究进展

炎症性肠病(IBD)是一组肠道慢性非特异性炎性疾病，其确切的病因不明。近年来，IBD的发病率逐年增高，IBD相关结直肠癌(IBD-CRC)是其一种严重的并发症。本文就IBD-CRC的流行病学、癌变机制、危险因素、监测和预防等内容作一简要综述。     

Toll样受体在炎症性肠病发病机制、并发症及治疗中的作用研究进展

炎症性肠病（IBD）是一种多因素导致的慢性非特异性自身免疫性疾病，发病机制复杂。Toll样受体（TLR）是模式识别受体，可诱导炎症反应。TLR在IBD中异常表达，在IBD的发生发展中占重要地位。TLR通过髓样分化因子（MyD88）依赖性通路和MyD88非依赖性通路影响肠黏膜屏障与免疫细胞分化，参与IBD的发生发展；TLR与IBD并发症密切相关，TLR下游炎症因子可促进肠纤维化，诱导炎症相关性结直肠癌，还可促进IBD患者血栓形成；临床可基于TLR基因多态性治疗IBD并判断预后，益生菌或内外源性调控物质可通过TLR通路改善IBD病情。     

5-ASA在炎症性肠病相关结直肠癌中的化学预防作用

癌变是溃疡性结肠炎(ulcerative colitis,UC)最严重的并发症,其预防手段包括内镜监测、分子生物标志物、手术治疗及化学预防。5-氨基水杨酸盐(5-aminosalicylic acid,5-ASA)是轻-中度UC患者的一线用药,其对炎症性肠病(inflammatory bowel disease,IBD)相关结直肠癌的化学预防作用及机制尚不十分明确。本文较全面地阐述5-ASA的化学预防作用及机制研究进展,旨在为临床实践中预防IBD相关癌变用药方案提供更多依据。     

纤维素饮食及其代谢产物与结直肠癌的化学预防

以合成或天然物质抑制癌前病变的发展是结直肠癌化学预防的重要环节。纤维素来源于植物成分．多项流行病学调查和临床试验结果证实高纤维素饮食可降低结直肠癌的发生率。纤维素的剂量、使用时机、时间长短及其种类均可影响癌变过程。纤维素饮食预防结直肠癌的机制包括纤维素在结肠中经厌氧菌发酵产生丁酸盐等短链脂肪酸（SCFA），通过抑制组蛋白脱乙酰基酶（HDAC）而提高抑癌基因p21^WAF1相关染色体活性，从而阻滞细胞周期。本文就纤维素饮食及其代谢产物与结直肠癌化学预防的相关研究结果作一简要分析。     

放大色素内镜联合窄带成像对炎症性肠病相关异型增生和结直肠癌的诊断价值

目的 探讨放大内镜联合靛胭脂染色和窄带成像技术（NBI），对炎症性肠病（IBD）相关的异型增生和结直肠癌的诊断价值。 方法 在长病程IBD患者结肠镜检查中，先后应用白光、NBI和靛胭脂染色放大观察，对可疑病变实施靶向活检或切除，以病理诊断为金标准评估该方法对IBD的筛查效果。 结果 共纳入长病程IBD患者45例，其中16例（17处病变）检出异型增生或癌，包括低级别异型增生12例（26.7％），高级别异型增生4例（8.9％），结肠癌1例（2.2％）。靶向活检的阳性率为13.2％（17／129）。NBI国际结直肠内镜（NICE）分型和工藤分型的检出率分别为81.3％（13／16）和75.0％（12／16），二者联合的检出率为100％。在合并异型增生和结肠癌的患者中，随着年龄增长（P=0.027）和病程延长（P=0.013），病变恶性程度有加重的趋势。高级别异型增生和结肠癌的病变直径［（2.5±1.4）cm］大于低级别异型增生［（0.6±0.4）cm］（P=0.003）。 结论 对于IBD相关异型增生和结直肠癌，放大色素内镜联合NBI可有效检出病变并判断其性质，为正确治疗奠定基础。     

5-氨基水杨酸在炎症性肠病及其相关性结直肠癌中的作用新机制

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）,5-氨基水杨酸（5-ASA）是IBD治疗中最经典的抗炎剂。IBD患者结直肠癌（CRC）的发病率较正常人群明显增高,长期使用5-ASA可减少IBD患者发生CRC的风险。5-ASA传统的抗炎机制是通过影响抑制前列腺素合成、调节各种细胞因子的产生而发挥抗炎作用的,新近研究发现5-ASA可能通过氧化物酶体增殖物激活受体（PPAR）-γ途径发挥抗炎和抗瘤作用。本文就5-ASA的作用新机制作一简要概述。     

5-氨基水杨酸类药物有效预防炎症性肠病合并结直肠癌

在工业化国家，溃疡性结肠炎(UC)的发病率维持在0．005％-0.01％．其中以瑞典最高，英国和美国次之，我国的UC发病率较低。克罗恩病(CD)的发病率在过去30年内增加了6倍。现约为0．004％。尽管IBD合并的结直肠癌只占普通人群结直肠癌的1％～2％，但结直肠癌仍为IBD的严重并发症，是1／6 IBD患者的死亡原因^[1]。Eaden等^[2]对116项     

Colorectal cancer in inflammatory bowel disease: Results of the 3rd ECCO pathogenesis scientific workshop (I)

Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.     

Mesalamine Protects Against Colorectal Cancer in Inflammatory Bowel Disease

Background  

Individuals with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC) compared with the general population. Previous studies show this risk is strongly associated with dysplasia, extent of disease, duration of disease, and degree of inflammation, while chemoprevention of CRC has less support.     

Dysplasia and colorectal cancer surveillance in inflammatory bowel disease

Introduction: Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used. However recent data suggests that chromoendoscopy is a better method of surveillance. Using 5-aminosalicylic acid agents primarily for chemoprevention is an ongoing debate however, when prescribed along with other strategies to control inflammation, their use is considered of benefit. This review presents current understanding of risk factors of neoplasia focusing on dysplasia and preventive strategies.

Areas covered: PubMed search was done using key words to assess current evidence. Along with genetics, risk factors, strategies that modify the risk of dysplasia, and CRC in IBD are discussed in detail.

Expert commentary: The role of our strategies in modifying CRC risk needs further assessment. Future research should aim to fill knowledge gaps such as high quality evidence for Chromoendoscopy and development of molecular markers for dysplasia detection. Our ultimate goal would be to eliminate CRC and is possible by better understanding of key pathogenic mechanisms in IBD.     

炎症性肠病合并血液系统肿瘤

炎症性肠病(IBD)合并血液系统肿瘤临床上较罕见。近年IBD患者中血液系统肿瘤的发病风险是否增加已受到越来越多的关注。多数研究认为免疫抑制剂尤其是嘌呤类似物可增加IBD患者淋巴瘤的发病风险,而IBD中白血病和骨髓增生异常综合征(MDS)的发病风险是否增加仍需进一步研究。IBD合并血液系统肿瘤的发病机制尚不明确,造血干细胞移植可能是其最佳的治疗选择。     

Has the risk of colorectal cancer in inflammatory bowel disease decreased?

The association between inflammatory bowel disease(IBD)and colorectal cancer(CRC)has been acknowledged for almost a century and is assumedly promoted by a chronic inflammation-driven carcinogenic process in the intestine in combination with a genetic predisposition.The magnitude of the risk of CRC in IBD remains a continuing subject of debate.The early,high risk estimates for CRC in IBD were most likely overestimated due to selected patient populations originating from tertiary referral centers with a disproportional high percentage of patients with severe disease.Later population-based studies calculating risk estimates from a broad spectrum of IBD patients have found the risk to be significantly lower.At present,there is evidence that IBD patients with longstanding and extensive disease with uncontrolled inflammation are those at increased risk.Additional,other recognized risk factors include early age at onset,family history of CRC,and concomitant primary sclerosing cholangitis.A significant amount of effort is put into identifying potential preventive factors of CRC in IBD,including surveillance programs and chemopreventive agents but the individual effect of these remains uncertain.Interestingly,recent studies have reported a decline in risk of CRC over time.Surveillance programs and the new treatment strategies,particular biological treatment might be part of the reason for the observed decline in risk of CRC in IBD over time but future studies will have investigate this assumption.     

From inflammation to colitis-associated colorectal cancer in inflammatory bowel disease: Pathogenesis and impact of current therapies

The risk of colorectal cancer (CRC) is higher in patients with inflammatory bowel disease (IBD). Population-based data from patients with ulcerative colitis (UC) estimate that the risk of CRC is approximately 2- to 3-fold that of the general population; patients with Crohn's disease appear to have a similar increased risk. However, the true extent of colitis-associated cancer (CAC) in undertreated IBD is unclear. Data suggest that the size (i.e., severity and extent) and persistence of the inflammatory process is largely responsible for the development of CRC in IBD. As patients with IBD and CRC have a worse prognosis than those without a history of IBD, the impact of current therapies for IBD on CAC is of importance. Chronic inflammation of the gut has been shown to increase the risk of developing CAC in both UC and CD. Therefore, control of inflammation is pivotal to the prevention of CAC. This review presents an overview of the current knowledge of CAC in IBD patients, focusing on the role of inflammation in the pathogenesis of CAC and the potential for IBD drugs to interfere with the process of carcinogenesis by reducing the inflammatory process or by modulating pathways directly involved in carcinogenesis.     

难治性炎症性肠病临床特征分析

背景：近年炎症性肠病（IBD）的发病率逐渐增高，对常规治疗反应差甚至无反应的患者亦逐渐增加，如何处理难治性IBD已成为临床医师面临的一大难题。目的：探讨难治性IBD患者的临床特征，从而提高对该病的认识和诊治水平。方法：收集1998年12月～2007年12月浙江中医药大学附属第一医院确诊的229例IBD患者。根据是否使用激素及其治疗结果，将人选患者分为难治组和有效组，比较两组患者的一般情况、临床症状、内镜表现、实验室检查结果和并发症情况。结果：难治组和有效组分别纳入26例和25例IBD患者，分别占总数的11．4％和10．9％。难治组患者首次接受全身糖皮质激素治疗前的中位病程显著长于有效组（18个月对7个月，P〈0．05）。两组临床症状、内镜表现和病变部位相比差异无统计学意义。起病时，难治组C反应蛋白（CRP）水平显著高于有效组[（45．5±36．8）mg/L对（19．2±15．3）mg／L，P〈0．05]，红细胞沉降率（ESR）水平显著高于有效组[（45．9±37．1）mm／h对（21．9±12．7）mm／h，P〈0．051，血清白蛋白显著低于有效组[（24．2±10．2）g／L对（33．4±7．6）g，L，P〈0．05]，且并发症发生率显著高于有效组（38．5％对4．0％，P〈0．05）。结论：难治性IBD临床症状和内镜表现与激素治疗有效的中-重度IBD无异，但接受激素治疗前的病程较长，起病时CRP、ESR和血清白蛋白水平与预后可能相关。     

炎症性肠病患者血浆TRAF1的表达及其临床意义

目的比较炎症性肠病患者血浆肿瘤坏死因子受体相关因子-1（tumor necrosis factor receptor-assoc iated factor-1,TRAF-1）水平和正常对照者的差异,分析血浆TRAF1水平对炎症性肠病的诊断价值以及与内镜下疾病活动性的相关性。方法共纳入62例克罗恩病患者、64例溃疡性结肠炎患者和56例正常对照者。应用酶联免疫吸附试验（Enzym e-linked immuno-sorbent assay,ELISA）分析炎症性肠病患者和正常对照者血浆中TRAF1蛋白的表达,受试者工作特征曲线（rece iver-operating characteristic,ROC）分析血浆TRAF1水平对克罗恩病和溃疡性结肠炎的诊断价值,应用Pearson相关分析研究血浆TRAF1水平与内镜下疾病活动性的相关性。结果克罗恩病患者（P=0.000）和溃疡性结肠炎患者（P=0.000）血浆TRAF1水平显著高于正常对照者,同时TRAF1对区分克罗恩病患者和正常对照者（P=0.000）以及区分溃疡性结肠炎患者和正常对照者（P=0.000）具有显著的诊断价值。克罗恩病患者血浆TRAF1表达水平和内镜下疾病活动指数呈较低的负相关（r=-0.260,P=0.041）,而溃疡性结肠炎患者血浆TRAF1水平与内镜下疾病活动程度无显著相关性（r=0.029,P=0.821）。结论炎症性肠病患者血浆TRAF1水平增高,血浆TRAF1水平对区分炎症性肠病患者和正常对照者具有诊断价值,但血浆中TRAF1的水平不能反应内镜下疾病活动程度。     

Reduction of colorectal cancer risk in patients with Crohn's disease

Patients with inflammatory bowel disease (IBD)-either Crohn's disease (CD) or ulcerative colitis (UC)-are at increased risk for developing cancers of the gastrointestinal tract, particularly colorectal cancer (CRC). Because of the relative rarity of IBD in the general population, it has been difficult to quantify this risk; nonetheless, within particular subsets of IBD patients, the cumulative risk of developing dysplasia and CRC may be substantial. Efforts to reduce this risk have included both prophylactic surgery and endoscopic screening programs. Despite the impact this disease has on quality of life and life expectancy, an optimal strategy for reducing the risk has yet to be defined. This article reviews the current literature relating to the risk of cancer for patients with IBD and methods available to help reduce this risk.     

Carcinogenesis in inflammatory bowel disease

Patients with longstanding ulcerative colitis (UC) and Crohn's disease (CD) have an increased risk of colorectal cancer (CRC). CRC accounts for approximately 15% of all deaths in patients with inflammatory bowel disease (IBD). The molecular pathway leading to CRC in IBD appears to differ from the well-known adenoma-to-CRC sequence, given the fact that these cancers appear to arise from either flat dysplastic tissue or dysplasia-associated lesions or masses. The risk of CRC for patients with IBD increases by 0.5-1% yearly, 8-10 years after diagnosis. Patients with a young age at disease onset, more extensive colitis, greater inflammatory burden, concomitant primary sclerosing cholangitis, and a family history of CRC are at greatest risk. Most cancers arise in pancolitis and there is little or no increased risk associated with proctitis while left-sided colitis carries an intermediate cancer risk. The CRC risk in patients with colonic CD is similar to that of UC. Colonic dysplasia is a precursor to CRC in IBD. There is no clear evidence that surveillance colonoscopy prolongs survival in patients with extensive colitis. Newer endoscopic and molecular techniques are being assessed for their effectiveness in augmenting conventional surveillance.