中国溃疡性结肠炎的研究现状与对策

1概况 溃疡性结肠炎(UC)1859年由Wilks首先描述,1920年被医学界公认,我国于1956年首次报道.过去认为该病欧美多见,亚非少见,但近几十年研究表明,UC在我国也是一种较常见的消化道疾病,并且正在逐渐成为消化病学研究的一个新热点,尽管我国目前还缺乏UC的流行病学资料,但据<世界华人消化杂志>2000年3月[1]对1978年以来几次重要的全国性消化会议的资料统计,该病发病率和患病率在我国有明显增加趋势:1978年杭州第一次全国消化系统疾病学术会议报告的病例为337例,1999年西安第六次全国消化系统疾病学术会议报告病例为例达1627例;1986年成都全国慢性腹泻研讨会报告的病例为581例,1996年江西全国肠病研讨会报告的病例为1412例;特别是1993年太原全国慢性非感染性肠道疾病学术研讨会上报告的病例达3065例,远远超过UC高发区全欧洲同期(1991/1993)新诊断的患者数1397例.     

中国溃疡性结肠炎10218例的特点

目的分析中国溃疡性结肠炎患者的特点.方法对从1981年到2000年20年间中国医学文献报告及我院确诊的1021 8例患者进行分析结果①病例数目20年间,中国医学文献报告及我院确诊的患者共10218例,其中最近10年报告的病例数目是前10年3.8倍.②病变范围直肠乙状结肠炎和直肠炎占70.20%,左半结肠炎占22.50%,广泛性或全结肠炎占7.30%.③病变类型初发型34.8%,慢性反复发作型52.6%,慢性持续性10.7%,急性暴发性1.9%.④病程75.5%患者小于5年,15.5%患者在5年和10年之间,只有9.1%患者大于10年.⑤肠外表现6.1%患者有肠外表现.⑥年龄发病的平均年龄是40.7岁(范围从6岁～80岁,高峰年龄段是30岁～49岁).⑦性别男女比是1.09.⑧吸烟病情严重程度和吸烟之间无负相关(P＞0.05),⑨家族遗传性270例患者中有4例有家族史.⑩治疗单纯采用西药(氨基水杨酸类或/和皮质激素)治疗的占18.6%,单纯采用中医治疗的占20.1%,采用中西医结合治疗的占59.1%,手术1.3%,其他治疗占0.9%.结论中国溃疡性结肠炎的病例数目在过去10年中显著增加,病变主要以左半结肠为主,病程短,肠外表现少见,发病年龄相对较大,男女比例数目大致相等,家族遗传少见,吸烟与病情轻重之间无显著相关,中医药治疗在中国广泛应用.     

溃疡性结肠炎的诊断、分型及疗效标准

1 溃疡性结肠炎的西医诊断、分型及疗效标准 我国在1978年杭州全国消化系统疾病学术会议上制定了第一个《特发性溃疡性结肠炎诊断及治疗标准(草案)》,后经1986年成都慢性腹泻会议,特别是经1993年太原全国慢性非感染性肠道疾病学术研讨会讨论修订后的新标准(太原标     

内镜下导管注药治疗重度溃疡性结肠炎

目的观察经内镜下注药对重度溃疡性结肠炎的治疗效果.方法随机对106例重度溃疡性结肠炎患者,应用内镜Bc-9L导管将中、西药物混合液直接注入病变部位进行治疗.选用药物锡类散、肿痛安、维生素、替硝唑、免疫抑制剂等.局部给药后,采取特殊体位,保留药液3h以上,1次/d,每4wk～6wk为一疗程.本组患者男72例,女34例,年龄20岁～73岁,其中30岁～59岁85例(80.2%),病程6mo～15a以上,临床表现多以腹痛、腹泻、粘液便或粘液血便为主.病变部位在直乙状结肠64例(60.37%),右半结肠24例(22.64%),全结肠18例(16.98%).结果经4wk～6wk治疗症状体征消失,镜检溃疡愈合86例(81.14%),症状体征基本消失,镜检溃疡范围缩小超过60%者10例(9.43%),症状体征有改善,镜检溃疡范围缩小未达50%者10例,视为无效,本组治疗有效率达90.6%.结论经内镜直接局部注药对重复溃疡性结肠炎有明显治疗作用.     

一氧化氮与溃疡性结肠炎

目的综述一氧化氮与溃疡性结肠炎的关系及研究进展,提高对一氧化氮在溃疡性结肠炎发病中重要性的认识.方法本文通过文献检索和查阅,回顾性总结近年国内外对一氧化氮与溃疡性结肠炎关系的研究进展,从三方面进行综述.结果①NO在溃疡性结肠炎患者体内的合成异常大量研究表明正常人群结肠粘膜既有cNOS又有iNOS,但肌层以cNOS为主;而UC患者结肠粘膜层则以iNOS为主,UC患者结肠粘膜iNOS活性增加与炎症程度呈平行关系.溃疡性结肠炎患者NO合成增加,iNOS活性增高,以致致癌性物质亚硝盐合成增多,是UC结肠癌发病率增高的原因之一.②NO在溃疡性结肠炎发病机制中的作用许多学者研究动物炎症损伤模型后发现,炎症初期NO抗炎作用表现在维持微循环完整性,松弛血管平滑肌,增加肠粘膜血流并抑制血小板、白细胞在内皮细胞表面粘附、积聚,防止血栓形成,同时抑制髓过氧化物酶活性,保护上皮屏障及促进上皮修复的作用.随着炎症的发展、持续,大剂量NO释放致组织、细胞损伤显得尤为突出.NO导致损伤作用的机制可能有三个途径.@在NO合成过程中,伴有超氧阴离子O2产生,合成过氧化亚硝酸盐(OONO),一旦质子化迅速蜕变为OH及NO2,具有很强的生物氧化性,可造成组织损伤.bNO是机体抵抗细胞内微生物及其他致病因子的第一道防线,能直接作用于微生物,也可用于启动免疫防御系统,若作用过强则造成自身正常组织损伤.CL-精氨酸通过NO介导细胞内传递、降低靶细胞内CAMP/CGMP比例,可激活NK,LAK细胞,直接增加两种细胞毒性;若作用过甚,势必造成正常组织损伤.③针灸治疗溃疡性结肠炎的iNOS基因调控表明,针灸可以抑制模型大鼠脾脏、结肠粘膜iNOSmRNA,IL-1βmRNA的表达,降低NO在组织中的浓度及组织细胞对炎症的反应性,从而有利于炎症的消除及组织的修复.结论溃疡性结肠炎是一种以直肠、结肠粘膜及粘膜下层炎症为特征的慢性非特异性炎症性肠病.合成异常的NO在炎症过程中充当了双重角色.既有其保护作用,又有杀伤毒性及促炎作用,这取决于NO产生部位、数量及作用持续时间.针灸可以降低NO在组织中的浓度及组织细胞对炎症的反应性,从而有利于炎症的消除及组织的修复.     

溃疡性结肠炎的其他治疗

氨基水杨酸类药物和皮质类固醇类药物目前仍然是治疗溃疡性结肠炎的主要药物,具有起效快,近期临床缓解率高等优点,但停药后易复发,长期用药副反应增多,部分顽固性患者疗效并不理想.中药是我国治疗溃疡性结肠炎的特色,中西医结合治疗是我国的优势,已被广泛应用,也已经取得了一定的效果,但疗效并无根本改善.因此,寻找更为理想有效,副反应少的药物和方法成为溃疡性结肠炎研究的重点.现将除上述治疗以外的其他一些有一定实用价值的药物和方法简单介绍如下:     

溃疡性结肠炎研究的新进展

病因和发病机制尚未阐明,未能建立理想的动物模型及治疗效果不够理想成为溃疡性结肠炎(UC)研究的难点和重点.近年来,在上述诸方面都取得了一些新进展,本文就此作一简述.     

重视消化系疾病大样本资料的分析研究总结

0 引言消化系疾病是常见病多发病,我国又是世界上人口最多的国家,因此,无论是发病率高的疾病,还是发病率低的疾病,患病人数的绝对值都是非常大的样本.对这些大样本资料进行分析研究总结,不仅有利于阐明某一疾病在我国的发病特点,诊治情况,而且对世界消化学的发展也具有重要意义.     

527例溃疡性结肠炎临床与病理分析

目的 评价临床、内镜及活检三者在溃疡性结肠炎(UC)诊断中的作用。方法 总结我院10年间经肠镜诊断为UC的病例，分析其临床、内镜表现及部分活检资料。结果 527例确诊为UC，其中误诊34例，结肠镜诊断正确率为93．9％。UC临床主要表现为腹泻(88％)、粘液脓血便(52％)。结肠镜表现以粘膜充血水肿(94％)、糜烂溃疡(75％)最多见，病变部位以直、乙结肠为主(51％)，呈弥漫性、连续性分布。活检特征性表现为炎症程度重(49％)，固有层弥漫性混合性炎细胞浸润(76％)、杯状细胞减少(71％)、隐窝扭曲(63％)、萎缩(47％)、隐窝炎(45％)、隐窝脓肿(36％)及绒毛状表面(39％)。结论 UC的诊断应强调临床、内镜及活检相结合。     

溃疡性结肠炎及克罗恩病的内镜活检病理特点分析

目的 总结溃疡性结肠炎（UC）及克罗恩病（CD）的病理形态学特点,为其诊断提供借鉴.方法 收集临床首次诊断并经病理科证实的UC患者180例、CD患者106例,资料包括年龄、性别及病变累及肠道的部位,并选用病理组织学标准对病变的黏膜结构改变、黏膜慢性炎症细胞浸润、黏膜急性炎症改变、黏膜上皮改变进行评价,比较两类患者间的差异.结果 和CD病例比较,UC病例出现黏膜结构紊乱的比例较高（P＜0.05）,出现局灶间断性炎症的比例较低（P＜0.05）,隐窝炎、隐窝脓肿及固有膜内中性粒细胞浸润发生率较高（P＜0.05）,表面上皮变扁或糜烂、黏液细胞减少的发生率较高.肉芽肿样小结、假幽门腺化生及裂隙状溃疡改变仅出现在CD病例.180例UC病例中90%（162例）病例病变部位局限于结肠.106例CD病例中28%（30例）病变部位局限于回盲部,56%（59例）病变累及到2个及以上不同部位.结论 肠镜活检病理诊断UC及CD是一个综合分析的过程.若病变局限于回盲部或胃肠道多部位累及,黏膜出现肉芽肿样小结、局灶间断性炎细胞浸润、假幽门腺化生等改变则倾向于CD诊断;若病变局限于结肠,黏膜出现弥漫一致性炎或明显的黏膜结构改变、黏膜上皮改变则倾向于UC诊断.     

MAGNIFYING COLONOSCOPY FOR THE DIAGNOSIS OF INFLAMMATORY CHANGES IN ULCERATIVE COLITIS

Background: Endoscopic observation is the most effective method for the evaluation of staging in ulcerative colitis (UC). However, in cases with very mild inflammatory activity, histopathological diagnosis may also be required. Unfortunately, biopsy‐related accidents are not uncommon. As an alternative, we have used a magnifying colonoscope commonly used for tumor diagnosis to examine in detail the colon mucosa of UC patients in clinical remission, and then compared these findings relative to conventional endoscopy using histopathological diagnosis. Subjects and Methods: Among UC cases examined by colonoscopy between April 2000 and April 2005, 27 cases without hematochezia for at least 1 month were enrolled in this study. Following observations of inflammatory changes using conventional colonoscopy, magnifying observation and biopsies at a total of 144 sites were evaluated. Using histopathological standards, acute‐phase inflammation was indicated by the presence of neutrophil infiltration, whereas chronic‐phase inflammation was indicated by infiltration of lymphocytes, plasma cells and eosinophils. Results: Indicators of significant inflammation by conventional observation was erosion. Under magnification, inflammation appears as superficial defects in mucosa and small whitish spots. When the presence of infiltrating neutrophils was used as a positive histological marker for inflammation, there was no difference in the accuracy of diagnosis by conventional observation (95.1%) versus magnifying observation (97.2%). In contrast, when lymphocyte infiltration was used as a marker, the accuracy of diagnosis increased significantly (88.2%) using magnifying observation relative to conventional observation (61.1%). Conclusions: Magnifying endoscopy can be used effectively in the evaluation of minute mucosal changes in cases of UC remission.     

Morphologic criteria applicable to biopsy specimens for effective distinction of inflammatory bowel disease from other forms of colitis and of Crohn's disease from ulcerative colitis

BACKGROUND: Inflammatory bowel disease (IBD)--and Crohn's disease (CD) and ulcerative colitis (UC) in particular--could be more reliably diagnosed by using biopsy criteria incorporating the colorectal distribution of specific histologic features. The aim of this study was to elucidate criteria distinguishing IBD from other forms of colitis (non-IBD), and CD from UC on the basis of multiple colorectal biopsies. METHODS: We examined multiple biopsy specimens (mean, 6.1) from 299 consecutive Japanese subjects with active colitis and performed multiple logistic regression analyses on 70 histologic features, from which 2 equations were constructed for the probabilities (P(IBD) and P(CD)) of a) IBD (versus non-IBD), and b) CD (versus UC), respectively, being present. On the basis of a receiver-operating characteristic curve, we determined four cut-off values for P(IBD) and constructed the criteria, consisting of the five categories 'definite IBD', 'probable IBD', 'unknown', 'probable non-IBD', and 'definite non-IBD'. The criteria for CD versus UC were constructed in a similar manner. Their validities were evaluated using 132 Canadian subjects. RESULTS: The statistically significant histologic features were as follows: for IBD, crypt architectural abnormalities, basal plasmacytosis with severe chronic inflammation, and distal Paneth cell metaplasia; for CD, segmental crypt architectural abnormalities and mucin depletion, mucin preservation at the active sites, and focal chronic inflammation without crypt atrophy. In the categories of probable IBD and probable non-IBD, both sensitivities and specificities exceeded 97%. Probable CD and probable UC showed high specificities of more than 97%, and their sensitivities were 94% and 89%, respectively. Kappa statistics showed these criteria to be sufficiently reproducible. CONCLUSIONS: Specific histological features together with their distribution can reliably diagnose IBD, distinguish CD from UC, and provide an estimate of the probability of the underlying disease being present.     

A Prospective Study of First Attacks of Inflammatory Bowel Disease and Infectious Colitis: Histologic Course during the 1st Year after Presentation

Schumacher G. Kollberg B, Sandstedt B. A prospective study of first attacks of inflammatory bowel disease and infectious colitis. Histologic course during the 1st year after presentation. Scand J Gastroenterol 1994:29:318-332.

To investigate the possibilities of differentiating between inflammatory bowel disease (IBD) and infectious colitis on histologic grounds, a prospective histologic study of 105 patients with a first attack of colitis was undertaken. Rectal biopsies were performed on four occasions during 1 year. The strongest predictor of IBD was basal plasmacytosis. followed by more than two vertical crypt branches per medium-power field, crypt distortion, villous mucosa, and mucosal atrophy. These signs were rarely found among patients with infectious colitis. Their frequency increased with the interval between initial symptoms and the first biopsy. To study the development of histologic features in the absence of treatment, the IBD patients were divided into groups depending on this interval. Focal or diffuse basal plasmacytosis increased from 38% in the group with an interval of 1-15 days to 89% in those who presented in 121-300 days, and crypt distortion from 0% to 78%, whereas absence of signs indicating IBD decreased from 62% to 11%. The presence of focal basal plasmacytosis seems to be the earliest sign of IBD. The frequency of histologic signs indicating IBD was maximal (88%) at the 1-week biopsy. After recovery, the basal plasmacytosis and villous mucosa decreased, whereas crypt distortion and mucosal atrophy remained unchanged. Early treatment did not prevent the appearance of any feature.     

溃疡性结肠炎与感染性结肠炎临床和病理比较分析

目的　比较溃疡性结肠炎 (UC)与感染性结肠炎 (IC)临床表现、内镜及组织学特点等方面的不同。方法　复习 1996～ 2 0 0 1年我院住院的 12 7例UC和 14 3例IC患者的临床资料 ,比较两组患者的临床表现及常规实验室检查指标 ;盲法比较其中 46例UC和 42例IC患者内镜及组织学表现。结果　两组患者的病程、起病方式、有无血便、诱因、腹痛、恶心呕吐、发热等比较差异有显著性 (P <0 .0 0 1)。血白细胞计数及血色素比较差异有显著性 (P <0 .0 0 1)。内镜表现中提示UC的指标为弥漫性分布、粗糙颗粒变、自发性出血、袋囊变浅、肠管短缩及息肉。提示IC的指标为病变呈灶性分布。组织学表现中弥漫性混合性或慢性固有层炎症、隐窝扭曲与分叉、隐窝萎缩、绒毛状表面、基底浆细胞增多有助于UC的诊断。结论　结肠镜及粘膜活检有助于UC和IC的诊断     

Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review

Upper gastrointestinal(UGI) tract involvement of inflammatory bowel disease(IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis(UC), atypical UC, Crohn's disease(CD) and IBD unclassified.Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid(non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD,is histologically characterized by increased intraepithelial lymphocytes(> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis,villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.     

Effects of sulfasalazine on biopsy mucosal pathologies and histological grading of patients with active ulcerative colitis

AIM: To investigate the mechanisms of sulfasalazine (SASP) in the treatment of ulcerative colitis (UC). METHODS: Changes of pathological signs and histological grading of 106 patients with active UC were observed before and after the treatment with SASP, 1 g, thrice daily for 6 wk. RESULTS: The effect of SASP on the vasculitis in lamina propria was 48.2% and 17.4% in the mild active UC (P<0.001) and 68% and 26.7% in the moderate active UC (P<0.001) before and after treatment. Fibroid necrosis of vessel wall was found in one case of mild UC and two cases of moderate UC before treatment and was not found after treatment. No thrombosis was found in mild UC before and after treatment, while thrombosis was found in one case of moderate UC before treatment. The effect on mucosal glandular abnormality was 30.4% and 13.0% in mild UC (P<0.05), and 42% and 40% in moderate UC (P>0.05) before and after treatment. The rate of eosinophil infiltration was 98.2% and 80.4% in mild UC (P<0.01), and 100% and 91.1% in moderate UC (P<0.05) before and after treatment. The effect on crypt abscess was 21.4% and 4.4% in mild UC (P<0.05), and 48% and 13.3% in moderate UC (P<0.001) before and after treatment. The effect on mucosal pathohistological grading was 2.00+/-0.84 and 0.91+/-0.46 in mild UC (P<0.001), and 2.49+/-0.84 and 1.31+/-0.75 in moderate UC (P<0.001) before and after treatment. CONCLUSION: SASP can improve small vessel lesions and crypt abscesses and reduce neutrophilic and eosinophilic leukocyte infiltration in inflammatory mucosa of UC.     

Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease

BACKGROUND AND AIM: Colorectal Paneth cell metaplasia (PCM) is known to be a sign of idiopathic inflammatory bowel disease (IBD), although its distribution and histogenesis are not fully understood. Objectives of this research were to investigate the spatial distribution of PCM in IBD and other forms of colitis (non-IBD), and to find stimuli causing PCM. METHODS: We studied multiple biopsy specimens from 181 patients with ulcerative colitis (UC), 159 with Crohn's disease (CD), 448 with non-IBD, and 78 normal controls. Paneth cell metaplasia frequency, at each colorectal site, was evaluated to find possible differences among diseases, phases of activity, and extents of disease. RESULTS: In non-IBD and controls, PCM was rarely (0-1.9%) seen at distal sites, but frequently (up to 48.7%) found at the ascending colon and cecum (P < 0.001). Paneth cell metaplasia frequency was significantly higher in IBD than in non-IBD patients and controls at distal sites (P < 0.001), but did not differ significantly between UC and CD, or among active, resolving, and quiescent phases. In UC, proctitis and left-sided colitis rarely displayed PCM at unaffected sites. Multiple logistic regression analysis revealed that PCM was positively associated with crypt distortion and mononuclear cell infiltration (P < 0.005), but negatively or not significantly associated with crypt atrophy, mucin depletion, acute inflammation, or phase of activity. CONCLUSIONS: Paneth cell metaplasia is a non-specific phenomenon in the proximal colon, but distal PCM, which occurs exclusively in affected mucosa, is a useful marker indicating IBD, even in the inactive phase. Regression analysis suggests that repair and regeneration may be the most potent stimuli causing PCM.     

缺血性结肠炎与溃疡性结肠炎临床诊断对比分析

目的对比分析缺血性结肠炎及溃疡性结肠炎临床特点与组织病理学的差异,为临床鉴别诊断提供依据。方法收集广西医科大学第一附属医院2010~2013年20例缺血性结肠炎及30例溃疡性结肠炎患者性别、病程、年龄、基础疾病史、临床表现,肠镜结果及病理特点等资料,并进行对比分析。结果缺血性结肠炎发病以60岁以上老年人为主,起病急,病程短,多伴有高血压、糖尿病等基础疾病,溃疡性结肠炎以中青年患者为主,病程长,伴随基础疾病较少见,前者临床表现以腹胀、呕吐多见,后者以黏液血便及里急后重症状较多见。缺血性结肠炎肠镜下病变较少累及直肠,多出现黏膜水肿,溃疡多呈纵行,溃疡性结肠炎常累及直肠,常合并炎性假息肉,溃疡以地图状为主,病变部位呈连续性。病理上,缺血性结肠炎以血管扩张充血、间质水肿及血管壁增厚多见,而炎性细胞浸润及隐窝脓肿较少见。结论结合年龄、既往病史、临床症状及内镜、组织病理学检查结果,有助于缺血性结肠炎与溃疡性结肠炎的鉴别诊断。