溃疡性结肠炎的方方面面

1、会计学1溃疡性结肠炎的方方面面溃疡性结肠炎的方方面面I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571607.nTurner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al. Management of pediatric ulcerative colitis: a joint ECCO and ESPGHAN evidence-based co

2、nsensus guidelines. J Pediatr Gastroenterol Nutr 2012.nTurner D, Travis SP, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, et al. Consensus for managing acute severe ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESP

3、GHAN. Am J Gastroenterol 2011;106:57488.nLike the initial Consensus on the management of Crohns disease, the current Consensus is grouped into three parts: definitions and diagnosis; current management; and management of special situations. nThis first section concerns aims, methods and definitions

4、of the Consensus, as well as classification, diagnosis, imaging and pathology of UC. nThe second section on current management includes treatment of active disease, maintenance ofmedically-induced remission and surgery of UC.nThe third section on special situations includes pouch disorders, cancer s

5、urveillance, pregnancy, paediatrics, psychosomatics, extra-intestinal manifestations and alternative therapy.and management of special situations.nPreviously included chapters on pregnancy and pediatrics are no longer included in this guideline, as specific ECCO Consensus Guidelines on Reproduction

6、and Pregnancy and Pediatric UC (together with ESPGHAN) cover these topics extensively.Ouyang QAPDW 2004 Chinese IBD working groupJ Gastroenterol Hepatol. 2007脂肪酸的细菌，这些细菌数量减少，导致维持肠上皮细胞生长和代谢的丁酸盐和其他短链脂肪酸等营养物质减少。同时。溃疡性结肠炎患者肠道内产硫化氢的细菌增多，硫化氢具有抑制丁酸盐和其他短链脂肪酸等营养物质生存及直接影响肠上皮细胞新陈代谢的功能。n上述细菌菌群失调导致肠上皮细胞营养缺乏，影响了肠

7、黏膜屏障功能。nDuchmann R。Kaiser I，Hermann E，et a1Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)Clin Exp Immunol，1995102：448455nFrank DN， St Amand AL， Feldman RA， et a1Molecularphylogenetic characterization of microbial community imbalances in hu

8、man inflammatory bowel diseasesProc Natl Acad Sci USA，2007，104：1378013785ulcerative colitis: results after control of smoking factor. Korean J. Gastroenterol. 1998; 32: 5560.nVleggaar FP, Lutgens MW, Claessen MM. Review article: the relevance of surveillance endoscopy in long-lasting inflammatory bo

9、wel disease. Aliment. Pharmacol. Ther. 2007; 26 (Suppl. 2): 4752.bloody diarrhea (“hematochezia”). nActive inflammatory anorectal lesions result in urgency of defecation and cramps around defecation (“tenesmus”). UC patients often complain of lower left quadrant pain. nExtraintestinal Manifestations

10、Wafik El-Diery and David Metz, Section EditorsDiagnostics of Inflammatory Bowel DiseaseGastroenterology，2007;133:16701689218694nReese GE, Constantinides VA, Simillis C et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclearantineutrophil cytoplasmic antibodies in infl

11、ammatory bowel disease. Am J Gastroenterol. 2006 (Oct); 101 (10): 241022.nBossuyt XSerologic markers in inflammatofy bowel diseaseC1in Chem 2006：52：171一181值均o05)。初步筛选出UC患者与健康对照者存在明显差异的39个蛋白点，选择其中9个点。经质谱分析发现触珠蛋白，热休克转录因子2，受体酪氨酸激酶、醛脱氢酶、载脂蛋白c一、中心粒旁物质l在UC患者中表达水平升高，角蛋白1，细丝蛋白A结合蛋白1、肌球蛋白3在UC患者中表达水平降低。n结论 采用

12、蛋白质组学2-DE和质谱技术，筛选并鉴定出与UC相关的9个血清蛋白质，为提供新的UC生物学行为研究分子标志物奠定基础。n缪应雷，等. 溃疡性结肠炎血清差异蛋白的筛选研究. 中华消化杂志. 2010 , 30 (12): 898-901.CMV的风险增加。结肠活检组织的炎症和溃疡部位可见CMV包涵体, 且研究发现生长旺盛的细胞如肉芽组织或溃疡深部更易发现CMV感染推测CMV可通过单核细胞到达炎症黏膜并可在黏膜内增殖且对炎症黏膜具有特殊亲和力。nCMV急性感染可显著提高血清和肠道自然杀伤细胞、白细胞介素(IL)6、TNF-a、IFN1水平提示CMV感染可改变黏膜免疫提高宿主对炎症的易感性nCMV感

13、染可激活原癌基因、激酶、转录因子致肿瘤发生。可能是IBD患者结直肠癌发病率较高的原因之一例。nMatsuoka K, 1wao Y，Mori T，et a1Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patientsAm J Gastroenterol，2007，102：331-337对照.通过聚合酶链反应( PCR)和Cd毒素快速测试试剂盒(CDTK)方法对粪便样本中毒素A、毒素B基因进行检测,采用SPSS软件进行统计分析.n结果

14、 纳入研究的130例IBD患者中,Cd感染者16例(12.3),其中UC 10例(16.7),CD 6例(8.6)；对照组中未发现Cd感染者(x2=15.779,P=0.000).处于活动期的IBD患者Cd感染率显著高于非活动期患者(x2=10.092,P=0.001).结肠型CD患者的感染率为4/14,显著高于其他类型的CD患者(x2=13.125,P=0.001).轻度UC患者Cd感染率为4.5、中度为14.3、重度为6/17(x2=6.667,P=0.037)；轻度CD患者的Cd感染率为0、中度为4.2、重度为5/16,感染率随疾病严重程度的上升而增高(x2=13.907,P=0.000

15、).使用广谱抗生素的患者与未使用者其Cd感染率差异无统计学意义(x2=1.414,p=0.378);免疫抑制剂与广谱抗生素同时使用者和单用广谱抗生素者Cd感染率差异亦无统计学意义(x2=0.330,P=0.962).n结论 IBD患者中存在着一定的Cd感染率,尤其是处于疾病活动期的患者,感染率随IBD疾病严重程度的上升而增高.n袁耀宗，等. 难辨梭状芽孢杆菌与炎症性肠病难辨梭状芽孢杆菌与炎症性肠病关系的初步研究关系的初步研究. 中华消化杂志. 2012， 32 (4)：88-89.in the secretions overlying most mucosal surfaces that in

16、teract directly with external pathogens, including saliva, tears, vaginal secretions, feces, synovial fluid, and mammalian breast milk. It is a major component of the secondary granules of polymorphonuclear neutrophils and is shown to be a primary factor in the acute inflammatory response. In the in

17、testinal lumen, fecal lactoferrin levels quickly increase with the influx of neutrophils during inflammation.nSugi and colleagues investigated lactoferrin, polymorphonuclear neutrophil (PMN) elastase, andlysozyme together with myeloperoxidase in fecal material and whole-gut lavage fluid from IBD pat

18、ients.nLanghorst J, Elsenbruch S, Mueller T et al. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm. Bowel Dis. 2005; 11: 108591.Judd TA，Day AS，Lemberg DA，et a1Update of fecal markers of inflammation in inflammatory bowel diseaseJ

19、Gastroenterol Hepat012011，26：14931499n检查所见的主要改变为：n(1)黏膜粗乱和(或)颗粒样改变；n(2)肠管边缘呈锯齿状或毛刺样，肠壁有多发性小充盈缺损；n(3)肠管短缩，袋囊消失呈铅管样。Ulcerative colitis with backwash ileitis. Axial CT enterographic sections show continuous involvement of the large bowel (white arrrows) and backwash ileitis (black arrow in b).Elsayes K

20、M，AIHawary MM，Jagdish J，et a1CT enterography：principles，trends，and interpretation of findingsRadiographics，2010，30：19551970Danese S，Fiocehi CUlcerative colitisN Engl J Med，2011365：1713 1725n 结肠镜检查并活组织检查(后文简称活检)是UC诊断的主要依据。n 结肠镜下UC病变多从直肠开始，呈连续性、弥漫性分布，表现为：n (1)黏膜血管纹理模糊、紊乱或消失，黏膜充血、水肿、质脆、自发或接触出血和脓性分泌物附着，

21、亦常见黏膜粗糙、呈细颗粒状；n (2)病变明显处可见弥漫性、多发性糜烂或溃疡；n (3)可见结肠袋变浅、变钝或消失以及假息肉、桥黏膜等。n (A) UC with mild inflammation and reduced haustration, vascular transparency is missing. n (B) Moderate inflammation with reduced haustration. The mucosa is edematous, covered with fibrin, and shows multiple erosions.n (C) Severe

22、inflammation with inflammatory narrowing of the lumen through pseudopolyps.n 内镜下黏膜染色技术能提高内镜对黏膜病变的识别能力，结合放大内镜技术，通过对黏膜微细结构的观察和病变特征的判别，有助UC诊断，n 姜泊，等放大内镜结合黏膜染色技术诊断溃疡性结肠炎附1 16例放大内镜形态分析现代消化及介入诊疗，2005，10：116118n Subtle lesions as seen at small-bowel capsule endoscopyn Bourreille A，Ignjatovic A，Aabakken L，e

23、t a1Role of smallbowel endoscopy in the management of patients with inflammatory bowel disease：an international OMED-ECCO consensusEndoscopy，2009，41：618637Riley SA, Mani V, Goodman MJ, et al. Microscopic activity in ulcerative colitis: what does it mean? Gut. 1991;32:174178.n (D, E) Crypt abscess in

24、 UC. (F) Pseudopolyp formation. L, lymph follicle.n Nikolaus S，Schreiber SDiagnostics of inflammatory bowel diseaseGastroenterology，2007，133：16701689Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol. Suppl. 1989; 170: 26;discussion 1619.夏冰，等. 缺血性结肠炎与溃疡性结肠炎的临床鉴别诊断.

25、 胃肠病学. 2010， 15(11)： 681-683.炎症性肠病诊断与治疗的共识意见（2012年广州）Truelove SC, Witts LJ. Cortisone in ulcerative colitis. Final report on a therapeutic trial. BMJ 1955;2:10411048.Satsangi J，Silverberg MS，Vermeire S，et a1The Montreal classification of inflammatory bowel disease：controversies，consensus，and implica

26、tionsGut2006，55：749753Satsangi J，Silverberg MS，Vermeire S，et a1The Montreal classification of inflammatory bowel disease：controversies，consensus，and implicationsGut2006，55：749753Stange EF，Travis SP，Vermeire S，et al，European evidence-based Consensus on the diagnosis and management of ulcerative colit

27、is：definitions and diagnosisJ Crohns Colitis，2008，2：123Baron JHConnell AMLennard-Jones JEVariation between observers in describing mucosal appearances in proctocolitisBr Med J. 1964。1：8992Travis SP, Schnell D, Krzeski P, AbreuMT, Altman DG, Colombel JF, et al. Developing an instrument to assess the

28、endoscopic severity of ulcerative colitis: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Gut 2012;61:53542.钱家鸣，等. 溃疡性结肠炎的临床表现和分型. 现代消化及介入诊疗. 2008， 13 (2)： 111-114.UC .nA number of parenteral corticosteroids have been tested in the treatment of severe UC . There was no obvious differen

29、ces in treatment response between the various steroidsnHowever, there was no evidence to support increasing the corticosteroid dose beyond 60 mg / day of methylprednisolone or equivalentnTruelove SC , Jewell DP . Intensive intravenous regimen for severe attacks of ulcerative colitis . Lancet 1974 ;

30、1 : 1067 70 .nTurner D , Walsh CM , Steinhart AH et al. Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a metaregression. Clin Gastroenterol Hepatol 2007 ; 5 : 103 110 .the ACT trial experience. Gut 2005;54(Suppl VII):A58.nReinisch W, Sandborn WJ,

31、Rutgeerts P, et al. Infliximab treatment for ulcerative colitis: comparable clinical response, clinical remission, and mucosal healing in patients with disease duration = 3 years. Gastroenterology 2008;134(Suppl 1):A495.nFidder HSchnitzler F， Rutgeerts P ，et a1 Longterm safety of inflixjmab for the

32、treatment of inflammatory boweI disease：a single center cohort studyGut2009，58(4)：50l-508nRutgeerts P, Vermeire S，Van Assehe GBiological therapies for inflammatory bowel diseasB Gastroenterology. 2009，136：l 1821197Gine JJ, Dolz C. Enteral nutrition in inflammatory bowel disease. Gut 1986; 27 (Suppl.

33、 1): 7680.nGonzalez-Huix F , Fernandez-Banares F , Esteve-Comas M et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis . Am J Gastroenterol 1993 ; 88 : 227 32 .nF, Gine JJ, Dolz C. Enteral nutrition in inflammatory bowel disease. Gut 1986; 27(Suppl. 1): 7680.nGon

34、zalez-Huix F , Fernandez-Banares F , Esteve-Comas M et al. Enteral versus parenteral nutrition as adjunct therapy in acute ulcerative colitis . Am J Gastroenterol 1993 ; 88 : 227 32 .nSherman PM，Ossa jc，JohnsonHenry KUnraveling mechanisms of action of probiotiesNutr Clin Pract，2009，24：1014nGuslandi

35、MAntibiotics for inflammatory bowel disease：do theywork? Eur J Gastroenterol Hepatol，2005，17：145-147nPerencevich M, Burakoff R. Use of antibioticsin the treatment of inflammatory bowel disease. Inflamm Bowel Dis. 2006; 12: 65164.nToruner M, Loftus EV Jr, Harmsen WS et al. Risk factors for opportunis

36、tic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 92936.cyclosporin appears to be as effective as 4 mg/kg/day and is thus preferred from the standpoint of safety.nLong term response rates following short term treatment with intravenous cyclosporin in controlled

37、trials ranged from 45% (without azathioprine maintenance) to 78% (with azathioprine).nThere is a small risk of opportunistic infection and death (12%) during combined cyclosporin, corticosteroid, and azathioprine therapy, but lower doses of cyclosporin may improve the safety profile.nToxicity may be

38、 reduced at a dose of 2 mg/kg/day intravenous cyclosporin.nLoftus CG，Loftus EV Jr，Sandborn WJCyclosporin for refractory ulcerativecolitisGUt2003，52; 172173nCheifetz AS，Stern JGarud Sel a1Cyclosporine is safe and effective in patients with severe ulcerative colitisJ Clin Gastroenter0120ll，45107 -11 2

39、nIts immunosuppressive effect appears to be mediated, in part, through inhibition of IL-2synthesis and release, as well as a decrease in the number of IL-2 receptors on activated lymphocytes.nAlthough its mode of action is similar to that of ciclosporin (CsA), the immunosuppressive effect is 30100 times greater in vitro and 1020 times greater in vivo than that of CsA.谢谢！and management of special situations.nPreviously included chapters on pregnancy and pediatrics are no longer included in this guideline, as specific ECCO Consensus Guidelines on Reproduction and Pregnancy a