1、Introduction vIBD是一種病因尚不十分清楚的慢性非特異性腸道炎癥，包括是一種病因尚不十分清楚的慢性非特異性腸道炎癥，包括UC和和CD 。v其發病率呈逐年上升趨勢，且多為青壯年發病，臨床表現復雜，并發癥嚴其發病率呈逐年上升趨勢，且多為青壯年發病，臨床表現復雜，并發癥嚴重，腸外表現多樣，嚴重影響個人生活質量和社會生產力。重，腸外表現多樣，嚴重影響個人生活質量和社會生產力。v此外，因其有癌變的風險，備受廣大醫生的重視。此外，因其有癌變的風險，備受廣大醫生的重視。v近年來在國內外近年來在國內外IBD基礎與臨床研究高潮迭起，基礎研究的成果直接指向基礎與臨床研究高潮迭起，基礎研究的成果直接指

2、向臨床治療，取得了劃時代的進展。臨床治療，取得了劃時代的進展。v探討和摸索適合國人的治療方案以降低重癥探討和摸索適合國人的治療方案以降低重癥UC的并發癥和死亡率顯得十分的并發癥和死亡率顯得十分重要。重要。Introduction vUlcerative colitis is characterized by mucosal inflammation of the colon. vThe pathology is inflammatory and the disease course is relapsing and remitting with intermittent symptoms of

3、 rectal bleeding and diarrhea.vApproximately 25% of patients develop a chronic active or a rapidly fulminate disease course.vChronic inflammation can lead to dysplasia and cancer. vApproximately 20% of patients require colectomy with ileoanal pouch or stoma.vVelayos FS, Terdiman JP, Walsh JM. Effect

4、 of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2005;100:13451353.ConsensusvStange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, et al. European evidence-based Consensus on the di

5、agnosis and management of ulcerative colitis: definitions and diagnosis. J Crohns Colitis 2008;2:123.vVan Assche G，Dignass A，Panes J，et a1The second European evidence-based Consensus on the diagnosis and management of ulcerative colitis：Definitions and diagnosisJ Crohns Colitis，20104：7 27vMowat C, C

6、ole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571607.vTurner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, et al. Management of pediatric ulcerative colitis: a joint ECCO and ESPGHAN evidence-

7、based consensus guidelines. J Pediatr Gastroenterol Nutr 2012.vTurner 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 Grou

8、p of ESPGHAN. Am J Gastroenterol 2011;106:57488.Management consensus of inflammatory bowel disease forthe AsiaPacific region 2006vAbstract: At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the AsiaPacific region, but several studies have shown an incr

9、eased incidence and prevalence of IBD in this region. vCompared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohns disease (CD). In addition to geographic differences, ethnic differences have been

10、 observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients.vIn general, the clinical course of IBD seems to be less severe in the AsiaPacific regi

11、on than in Western countries.vDiagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. S

12、o far,vWestern diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary t

13、o obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. vThe management of IBD also poses some special problems in the AsiaPacific Region. There is often a delay in using proper medications for IBD, and alternative l

14、ocal remedies are still widely used. With a combination ofWestern guidelines and regional experiences, similar principles can be used for induction and maintenance of remission.A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensi

15、ve and individualized approaches are suggested for different IBD patients. vDeeper understanding of disease pathogenesis and the unique characteristics of IBD in the AsiaPacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents woul

16、d improve the therapeutic outlook of IBD in this region.The Asia-Pacific consensus on ulcerative colitis 2010European evidence-based consensus on the diagnosis/management of ulcerative colitis 2008vThis document sets out the current European Consensus on the diagnosis andmanagement of UC, reached by

17、 the European Crohns and Colitis Organisation (ECCO) at a meeting held in Berlin on 20th October 2006. vECCO is a forum for specialists in inflammatory bowel disease from 23 European countries. vLike the initial Consensus on the management of Crohns disease, the current Consensus is grouped into thr

18、ee parts: definitions and diagnosis; current management; and management of special situations. vThis first section concerns aims, methods and definitions of the Consensus, as well as classification, diagnosis, imaging and pathology of UC. vThe second section on current management includes treatment

19、of active disease, maintenance ofmedically-induced remission and surgery of UC.vThe third section on special situations includes pouch disorders, cancer surveillance, pregnancy, paediatrics, psychosomatics, extra-intestinal manifestations and alternative therapy.2nd European evidence-based consensus

20、 on the diagnosis/management of ulcerative colitis 2012vThis document updates the previous European Consensus on the diagnosis and management of UC, and was finalised by the European Crohns and Colitis Organisation (ECCO) at a meeting held in Dublin in February 2011. vECCO is a forum for specialists

21、 in inflammatory bowel disease from 31 European countries. vLike the initial Consensus on the diagnosis and management of ulcerative colitis,68 this updated Consensus is grouped into three parts: definitions and diagnosis; current management; and management of special situations.vPreviously included

22、 chapters on pregnancy and pediatrics are no longer included in this guideline, as specific ECCO Consensus Guidelines on Reproduction and Pregnancy and Pediatric UC (together with ESPGHAN) cover these topics extensively.Backgroundv潰瘍性結腸炎（UC）1859年由Wilks首先描述，1920年被醫學界公認，我國于1956年首次報道。v特發性潰瘍性結腸炎診斷及治療標準（

23、草案）（1978年杭州）v潰瘍性結腸炎的診斷及療效標準（1993年太原）v對潰瘍性結腸炎診斷治療規范的建議（2000年杭州）v對我國炎癥性腸病診斷治療規范的共識意見（2007年濟南）v炎癥性腸病診斷與治療的共識意見（2012年廣州）v從中可以看出每一次補充和修改都反映了我國對該病認識的逐步提高，治療逐漸規范化。第九屆中華消化病學分會炎癥性腸病學組成員名單 v名譽組長：歐陽欽 v組長：胡品津 v副組長：錢家嗚 夏 冰 吳開春 冉志華 v秘書：王玉芳 高 翔 v核心成員：胡品津 歐陽欽 鄭家駒 錢家嗚 夏 冰 吳開春 冉志華 劉占舉 鐘 捷 吳小平 陳旻湖 胡仁偉 v組員：歐陽欽 鄭家駒 鄧長生

24、劉新光 胡品津 錢家鳴 夏 冰 吳開春 李俊霞 呂愈敏 顧 芳 劉玉蘭 王曉娣 韓 英 朱 峰 冉志華 劉占舉 鄭 萍 鐘 捷 龐 智 曹 茜 陳旻湖 智發朝 姜 泊 張亞歷 鐘英強 沙衛紅胡仁偉 王玉芳 甘華田 鄒開芳 吳小平 繆應蕾 江學良 于成功 梅 俏 王承黨 郭長存 盧雪峰 高 翔 霍麗娟Ulcerative colitis in China: Retrospective analysis of 3100hospitalized patientsvBackground & Aims: This retrospective study analyzed the clinical cha

25、racteristics of hospitalized patients with ulcerative colitis (UC) in China.vMethods: A total of 3100 hospitalized patients with UC admitted to 23 hospitals in China from 1990 to 2003 were retrospectively investigated and their clinical characteristics were analyzed.vResults: A male/female ratio of

26、1.34/1.00 was found in the 3100 patients, who had an average age of 44 15.1 years at diagnosis. Of the patients, 2972 (95.9%) had active UC. Active UC was mild in 35.4% of the 2972 patients, moderate in 42.9% and severe in 21.7%. Of the 2726 patients with a description of their lesion extent, 14.8%

27、had proctitis, 26.4% had proctosigmoiditis, 25.0% had left-sided colitis, 6.3% had extensive colitis, 25.8% had pancolitis and 1.7% had regional colitis. The predominant complaints of the patients with UC were bloody diarrhea (48.2%), abdominal pain (67.3%) and mucus stools (58.4%). Among these pati

28、ents, 13.6% had extraintestinal manifestations and 9.6% had related complications. A differential diagnosis was difficult to make, as there were 19 varieties of the disease; infectious enterocolitis had a misdiagnosis rate of 22.9% before admission. The main medications for UC in China were aminosal

29、icylates (66.8%) and steroids (42.8%). Only 94 (3%) of the patients required colectomy and only 19 (0.6%) died of UC.vConclusions: Compared with UC in Western countries, ulcerative colitis in China has some differences in clinical characteristics. Therefore, a further population-based epidemiologica

30、l study is required to determine the prevalence and incidence rates of UC in China.Ouyang QAPDW 2004 Chinese IBD working groupJ Gastroenterol Hepatol. 2007EpidemiolgyvThe incidence of UC ranged from 1.0 to 2.0 per 100 000 person years. The prevalence of UC has ranged from 4.0 to 44.3 per 100 000. vI

31、n a recent study, the speculated prevalence was 11.6/100 000 in China.vCompared to time trends in the West, there appears to be a time lag phenomenon involving incidence and and prevalence of IBD with regard to the Asian experience.vOuyang Q, Tandon R, Goh KL et al. Management consensus of inflammat

32、ory bowel disease for the Asia-Pacific region. J Gastroenterol. Hepatol. 2006; 21: 177282.vLennrd-Jones JE. Incidence of infammatory bowel disease across Europe:is there a difference between north and south?. Gut 1996; 39: 690-697. Etiology and Pathogenesisv目前對IBD病因和發病機制的認識可概括為：v環境因素作用于遺傳易感者，在腸道菌群叢的

33、參與下，啟動了腸道免疫系統及非免疫系統，最終導致免疫反應和炎癥過程。v可能是由于抗原的持續刺激或（及）免疫調節紊亂，這種免疫炎癥反應表現為過度亢進或難于自限。vBaumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet 2007;369:16271640. vBrown SJ，Mayer IThe immune response in inflammatory bowel diseaseAm J Gastroenterol，2007，102：20582069vBernstein CN，

34、Shanahan FDisorders of a modern lifestylel reconciling the epidemiology of inflammatory bowel diseasesGut，2008，57：1185-1191菌群失調vIBD患者腸遭細菌存在菌群失調，正常細菌數量減少，而致病菌、條件致病菌數量明顯增多。vDuchmann等 發現。正常人對其體內腸道菌群及抗原物質耐受，而IBD患者腸黏膜免疫細胞對失調的腸道菌群及抗原物質失去了耐受。這一發現證實了IBD患者腸道菌群及抗原物質能誘導腸黏膜異常免疫反應。vFrank等 發現IBD患者腸道菌群中擬桿菌、厚壁菌類減少，

35、而變形桿菌及放線菌等增多。由于在腸道內，擬桿菌、厚壁菌是主要的裂解食物纖維產生丁酸鹽和其他短鏈脂肪酸的細菌，這些細菌數量減少，導致維持腸上皮細胞生長和代謝的丁酸鹽和其他短鏈脂肪酸等營養物質減少。同時。潰瘍性結腸炎患者腸道內產硫化氫的細菌增多，硫化氫具有抑制丁酸鹽和其他短鏈脂肪酸等營養物質生存及直接影響腸上皮細胞新陳代謝的功能。v上述細菌菌群失調導致腸上皮細胞營養缺乏，影響了腸黏膜屏障功能。vDuchmann R。Kaiser I，Hermann E，et a1Tolerance exists towards resident intestinal flora but is broken in

36、active inflammatory bowel disease (IBD)Clin Exp Immunol，1995102：448455vFrank DN， St Amand AL， Feldman RA， et a1Molecularphylogenetic characterization of microbial community imbalances in human inflammatory bowel diseasesProc Natl Acad Sci USA，2007，104：1378013785Family historyvKitahora et al. found a

37、 strong familial occurrence in UC among Japanese patients. In a Korean study, a similar familial aggregation was also reported.vKitahora T, Utsunomiya T, Yokota A. Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committe

38、e of Inflammatory Bowel Disease in Japan. J. Gastroenterol. 1995; 30 (Suppl. 8): 58.vPark ER, Yang SK, Myung SJ et al. Familial occurrence of ulcerative colitis in Korea. Korean J. Gastroenterol. 2000; 36: 7704.Risk factorsvObjective To screen the risk factors of inflammatory bowel disease(IBD)by ca

39、se investigationvMethords 72 determined IBD patients and 72 paired healthy subjects were surveyed with an organized inventory comprising of relevant items to IBDCOX regression method was used to screen the statistically significant risk factors for IBDvResults COX regression indicated the statistica

40、l significance in stressmilk and fried food over the other postulated risk factorsfor IBDvConclusion Stress，milk and fried food are the potential risk factors for IBDvKaichun Wu et al. Investigation on the risk factors of inflammatory bowel disease：A paired study of 72 cases. Chin J Gastroenterol He

41、patol. 2006, 15(2): 161-162Protective factorsvA study from Japan found a protective effect of smoking for UC. Nam et al. found that appendectomy was protective against UC in their group of Korean patients.vA case-control study of ulcerative colitis in relation to dietary and other factors in Japan.

42、The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J Gastroenterol. 1995; 30 (Suppl. 8): 912.vNam SW, Yang SK, Jung HY et al. Appendectomy and the risk of developing ulcerative colitis: results after control of smoking factor. Korean J. Gastroenterol. 1998; 32:

43、5560.vVleggaar FP, Lutgens MW, Claessen MM. Review article: the relevance of surveillance endoscopy in long-lasting inflammatory bowel disease. Aliment. Pharmacol. Ther. 2007; 26 (Suppl. 2): 4752.Clinical PresentationvIntestinal Symptomsv70% of patients with UC report 5 bowel movements during acute

44、phases. vThe main reason for diarrhea is colonic inflammation, but bile acid and food malabsorption secondary to inflammation in the terminal ileum or the proximal small bowel can contribute to this symptom. vA history of surgical resections can be seminal in explaining symptoms. vAcute phases of UC

45、 almost always present with bloody diarrhea (“hematochezia”). vActive inflammatory anorectal lesions result in urgency of defecation and cramps around defecation (“tenesmus”). UC patients often complain of lower left quadrant pain. vExtraintestinal ManifestationsWafik El-Diery and David Metz, Sectio

46、n EditorsDiagnostics of Inflammatory Bowel DiseaseGastroenterology，2007;133:16701689腸外表現(Extraintestinal manifestations)v腸外表現包括：v皮膚黏膜表現(如口腔潰瘍、結節性紅斑和壞疽性膿皮病)v關節損害(如外周關節炎、脊柱關節炎等)v眼部病變(如虹膜炎、鞏膜炎、葡萄膜炎等)、v肝膽疾病(如脂肪肝、原發性硬化性膽管炎、膽石癥等)v血栓栓塞性疾病等。v Mendoza JL, Lana R, Taxonera C et al. Extraintestinal manifestati

47、ons in inflammatory bowel disease: differences between Crohns disease and ulcerative colitis. Med. Clin. (Barc.) 2005; 125: 297300.并發癥(Complications)v并發癥包括：v中毒性巨結腸 （toxic megacolon）v腸穿孔v下消化道大出血v上皮內瘤變和癌變v錢家鳴, 等.潰瘍性結腸炎合并中毒性巨結腸六例及文獻復習. 中華內科雜志J. 2012，51(9): 694-697/vChow DK，Leong RW，Tsoi KK, et a1Longte

48、rm followup of ulcerative colitis in the Chinese populationAm J Gastroenterol，2009，104：647-654Serological markersvThe two most widely studied serological markers in inflammatory bowel disease in recent years have been p-ANCA and ASCA. The clinical utility of p-ANCA or ASCA testing in the diagnosis o

49、f inflammatory bowel disease, in patients with non-specific gastrointestinal symptoms, is limited because of the varying seroprevalence of these antibodies in patients with inflammatory bowel disease and the inadequate sensitivity of the assays.vLawrance IC, Murray K, Hall A, Sung JJ, Leong R. A pro

50、spective comparative study of ASCA and pANCA in Chinese and Caucasian IBD patients. Am. J. Gastroenterol. 2004; 99: 218694vReese GE, Constantinides VA, Simillis C et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflamma

51、tory bowel disease. Am J Gastroenterol. 2006 (Oct); 101 (10): 241022.vBossuyt XSerologic markers in inflammatofy bowel diseaseC1in Chem 2006：52：171一181Serum proteinsv目的 應用蛋白質組學尋找潰瘍性結腸炎(UC)血清差異蛋白，初步探索UC可能的生物標志物。v方法 收集UC患者30例和健康對照者30名的血清標本，雙向凝膠電泳(2-DE)分離等量混合血清的蛋白質，運用圖像分析軟件進行比較和分析，識別差異表達蛋白質。應用基質輔助激光解吸電

52、離飛行時間質譜(MAI，DI-TOF-MS)鑒定部分差異蛋白質點。v結果 UC組和對照組之間年齡、體重指數、吸煙情況和飲滔量的差異均無統計學意義(P值均o05)。初步篩選出UC患者與健康對照者存在明顯差異的39個蛋白點，選擇其中9個點。經質譜分析發現觸珠蛋白，熱休克轉錄因子2，受體酪氨酸激酶、醛脫氫酶、載脂蛋白c一、中心粒旁物質l在UC患者中表達水平升高，角蛋白1，細絲蛋白A結合蛋白1、肌球蛋白3在UC患者中表達水平降低。v結論 采用蛋白質組學2-DE和質譜技術，篩選并鑒定出與UC相關的9個血清蛋白質，為提供新的UC生物學行為研究分子標志物奠定基礎。v繆應雷，等. 潰瘍性結腸炎血清差異蛋白的篩

53、選研究. 中華消化雜志. 2010 , 30 (12): 898-901.尿白蛋白v目的： 探討炎癥性腸病患者尿中白蛋白的臨床意義。v方法：對臨床確診的32例IBD患者（UC 27例，CD 5 例 ) 在疾病的不同時期，用免疫放射比濁法測定尿中白蛋白，并結合臨床 Harvey 和 Bradshaw 指數進行綜合分析，選取25例健康人為正常對照。v結果：患者尿白蛋白活動期比緩解期明顯增高（0.002）， Harvey 和 Bradshaw 指數呈正相關（活動期 r=0.76, P0.001；靜止期 r=0.73, P0.001）?；颊吣蛑邪椎鞍酌黠@高于正常人（活動期 P0.001, 緩解期, P

54、0.005）。v結論： 患者尿中白蛋白可作為判斷患者疾病活動情況的指標。v鄧長生. 炎癥性腸病患者尿白蛋白的臨床意義. 武漢大學學報. 2002， 23 (1)： 88-89.巨細胞病毒(CMV)v巨細胞病毒(CMV)屬皰疹病毒科B屬雙鏈DNA病毒，近年隨著IBD與CMV研究的深入，發現CMV在IBD的發生和疾病進展中起一定作用，且對IBD的臨床診治亦有一定指導價值。vPfau 等發現CMV更易感染肉芽組織生長細胞CMV對炎癥的趨向性使IBD患者感染CMV的風險增加。結腸活檢組織的炎癥和潰瘍部位可見CMV包涵體, 且研究發現生長旺盛的細胞如肉芽組織或潰瘍深部更易發現CMV感染推測CMV可通過單

55、核細胞到達炎癥黏膜并可在黏膜內增殖且對炎癥黏膜具有特殊親和力。vCMV急性感染可顯著提高血清和腸道自然殺傷細胞、白細胞介素(IL)6、TNF-a、IFN1水平提示CMV感染可改變黏膜免疫提高宿主對炎癥的易感性vCMV感染可激活原癌基因、激酶、轉錄因子致腫瘤發生?？赡苁荌BD患者結直腸癌發病率較高的原因之一例。vMatsuoka K, 1wao Y，Mori T，et a1Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patientsA

56、m J Gastroenterol，2007，102：331-337難辨梭狀芽孢桿菌 （Clostridium difficile ）v目的 通過對炎癥性腸病(IBD)患者糞便中難辨梭狀芽孢桿菌(Cd)的檢測,了解IBD患者中該菌的感染情況及其與IBD的關系.v方法 收集2009年12月至2011年1月上海交通大學醫學院附屬瑞金醫院消化科確診的IBD患者130例,包括潰瘍性結腸炎(UC)患者60例及克羅恩病(CD)患者70例.同時收集腸易激綜合征(IBS)患者及無腸道疾患的健康人群各60例為對照.通過聚合酶鏈反應( PCR)和Cd毒素快速測試試劑盒(CDTK)方法對糞便樣本中毒素A、毒素B基因

57、進行檢測,采用SPSS軟件進行統計分析.v結果 納入研究的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)；對照組中未發現Cd感染者(x2=15.779,P=0.000).處于活動期的IBD患者Cd感染率顯著高于非活動期患者(x2=10.092,P=0.001).結腸型CD患者的感染率為4/14,顯著高于其他類型的CD患者(x2=13.125,P=0.001).輕度UC患者Cd感染率為4.5、中度為14.3、重度為6/17(x2=6.667,P=0.037)；輕度CD患者的Cd感染率為0、中度為4.2、重度為5/16,感染率隨疾病嚴重程度的

58、上升而增高(x2=13.907,P=0.000).使用廣譜抗生素的患者與未使用者其Cd感染率差異無統計學意義(x2=1.414,p=0.378);免疫抑制劑與廣譜抗生素同時使用者和單用廣譜抗生素者Cd感染率差異亦無統計學意義(x2=0.330,P=0.962).v結論 IBD患者中存在著一定的Cd感染率,尤其是處于疾病活動期的患者,感染率隨IBD疾病嚴重程度的上升而增高.v袁耀宗，等. 難辨梭狀芽孢桿菌與炎癥性腸病難辨梭狀芽孢桿菌與炎癥性腸病關系的初步研究關系的初步研究. 中華消化雜志. 2012， 32 (4)： 88-89.Fecal markersvCalprotectin (FCP),

59、 a heterocomplex of S100A8 and S100A9, is a calcium-binding protein with antimicrobial protective properties derived predominately from neutrophils, and to a lesser extent, from monocytes and reactive macrophages. It constitutes approximately 5% of the total protein and up to 60% of the cytosolic pr

60、otein in human neutrophils. As such, the fecal calprotectin concentration is proportional to the influx of neutrophils into the intestinal tract, a hallmark of active IBD.vLactoferrin is an iron-binding glycoprotein identified in the secretions overlying most mucosal surfaces that interact directly