克罗恩病的发病机制和治疗进展

克罗恩病（Crohn＇s disease,CD）是一种以小肠为主,累及全层节段性全胃肠道的非特异性炎症性肠道疾病（inflammatory bowel disease,IBD）。该病须与溃疡性结肠炎、急性感染性结肠炎等鉴别诊断。该病存亚洲的发病率远低于西方国家,近10年来在我国的发病率有明显上升趋势。CD的病因与发病机制尚不明确,临床表现也复杂多样,且容易误诊,复发率高。在过去的10多年里,遗传和肠道免疫领域取得的研究成果为我们在研究IBD病因以及治疗上提供了新的思路。本文就CD的发病机制和治疗进展作一综述。     

Pathogenesis of postoperative recurrence in Crohn's disease

The majority of patients with Crohn's disease (CD) require surgery during the course of their disease, but such surgery is typically not curative. Although some studies suggest that the disease state is theoretically reset to its earliest phase following surgery, disease phenotype and natural history of CD do not change significantly after surgery, leading to high rates of recurrence. Factors predisposing to this recurrence are not well defined, so there is a need for and a unique opportunity to develop a better understanding of the pathogenesis of recurrent inflammation and associated risk factors after an ileocolic resection. This paper reviews the postoperative disease outcome and evolution based on defining the combination of the patient's microbial flora, environmental exposure history, immune response and genetic make-up.     

克罗恩病肠道纤维化的发生机制和临床治疗

肠道纤维化是克罗恩病的特征表现,其反复发作导致的肠道狭窄是克罗恩病最严重的并发症之一,目前治疗手段有限.本文对克罗恩病肠道纤维化发生机制及目前治疗手段进行综述.     

Pathogenesis of gall stones in Crohn's disease: an alternative explanation.

The increased prevalence of gall stones in Crohn's disease is thought to be related to depletion of the bile salt pool due either to terminal ileal disease or after ileal resection. This study was designed to examine whether this hypothesis is correct and explore alternative explanations. Two hundred and fifty one randomly selected patients (156 females, 95 males, mean age 45 years) were interviewed and screened by ultrasonography to determine the prevalence of gall stones in a large population of patients with Crohn's disease. Sixty nine (28%) patients had gall stones proved by ultrasonography (n = 42), or had had cholecystectomy for gall stone disease (n = 27). The risk factors for the development of gall stones including sex, age, site, and duration of disease, and previous intestinal resection were examined by multivariate analysis. Age and duration of disease were positive risk factors for gall stones and were covariables. The site of disease and of previous intestinal resection did not predispose to gall stones. Previous surgery was an independent risk factor for the development of gall stones, the risk increasing with number of laparotomies. It is suggested that mechanisms other than ileal dysfunction may predispose to gall stones. Postoperative gall bladder hypomotility with biliary sludge formation may be precursors of gall stone formation in patients with Crohn's disease.     

Endoscopy and Crohn's Disease: Endoscopic Approach to the Pathogenesis of Crohn's Disease

Abstract: This review describes endoscopic and histopathological findings in Crohn's disease with reference to its pathogenesis. The number of patients with Crohn's disease has markedly and rapidly increased during the last 10 years in Japan. Minute lesions such as aphthoid ulcers as an early lesion in Crohn's disease were at first discussed endoscopically and histopathologically. Recent advances concerning the mechanism of how aphthoid ulcers may occur revealed that they are induced by mucosal ischemia due to vasculitis. Longitudinal ulcers and cobblestone appearance were observed only in advanced Crohn's disease. Finally, the etiology of Crohn's disease was reviewed from the viewpoint of infectious agents and immunological abnormalities which were clarified from the study of endoscopic biopsy specimens.     

Crohn's disease

One theory of the pathogenesis of Crohn's disease is that rather than being caused by a unique environmental agent, it is the result of an abnormal immune response in the gastrointestinal tract. Recent studies indicate that Crohn's disease in its early stages is frequently associated with the presence of circulating antigen-non-specific suppressor T cells. Such T cells are also found in experimental inflammation caused by Chlamydia organisms in the gastrointestinal tract of nonhuman primates. Taken together, these data suggest that the suppressor T cells are markers of an underlying and persistent, antigen-specific immune response to an as yet unidentified antigen or set of antigens. We postulate that this underlying antigen-specific response is the result of a primary immunoregulatory abnormality involving an imbalance between the effects of antigen-specific helper and suppressor T cells which recognize a common antigen or antigens present in the mucosal environment.     

The dilemma of Crohn's disease: Crohn's disease and appendectomy

Conclusion The results of our clinical study, generally supported by the recent literature and a consensus of colorectal surgeons, indicate that an appendectomy can safely be performed in the presence of Crohn's ileitis. When fistulas do occur, they originate in the small bowel and not in the appendiceal stump. Non-granulomatous appendicitis does occur in the course of regional enteritis. The advantage of appendectomy in the face of regional enteritis is that it simplifies evaluation of abdominal pain in the future.     

Polymorphism of monocyte chemoattractant protein 1 in Crohn's disease

BACKGROUND AND AIMS: The chemokine MCP-1 is thought to be important for the recruitment of mononuclear cells and the maintenance of inflammation in inflammatory bowel disease. We investigated whether MCP-1 protein expression is correlated with the degree of mucosal inflammation in patients with Crohn's disease. Furthermore, we studied whether a functional single nucleotide polymorphism (G or A) located in the distal regulatory region of the MCP-1 gene is associated with Crohn's disease and/or its phenotype. PATIENTS AND METHODS: MCP-1 concentration in tissue homogenates was analyzed in mucosal biopsy specimens of 31 patients with Crohn's disease and 48 controls by enzyme-linked immunosorbent assay, and the correlation with an endoscopic macroscopic score was analyzed. In 179 patients with Crohn's disease and 189 controls MCP-1 genotyping was carried out by polymerase chain reaction restriction fragment length polymorphism technique. Subgroup phenotypic analysis was performed according to the Vienna classification. RESULTS: MCP-1 tissue concentrations were significantly associated with the macroscopic degree of inflammation. The gene frequency of the different MCP-1 alleles did not differ from healthy controls. However, the G/A and G/G genotype was significantly decreased in patients with a later onset of the disease and both genotypes presented also less frequently with a fistulizing disease behavior. CONCLUSION: The degree of intestinal inflammation in Crohn's disease is associated with MCP-1 tissue levels. Furthermore there is evidence for an association of different disease behavior with different MCP-1 genotypes.     

The dilemma of Crohn's disease: Ileoduodenal fistula complicating Crohn's disease

Summary Nine cases of duodenal fistula complicating Crohn's disease are reported. All nine patients were male. Four patients had Crohn's disease of the ileum and five had ileocolitis. No patient had primary duodenal Crohn's disease. Because attempt at primary closure of the duodenal defect may fail, our treatment of choice has been formal cross-cut two-layered duodenojejunal anastomosis with extensive drainage of the area postoperatively. This treatment has been associated with no mortality and little morbidity, and no late recurrence of duodenal fistula. Formerly Special Fellow at the Cleveland Clinic Hospital, Cleveland, Ohio.     

Perianal Crohn's disease

PURPOSE: This study relates our experience with local surgical management of perianal Crohn's disease. METHOD: Of 1,735 patients with Crohn's disease seen between 1980 and 1990, records of 66 patients (3.8 percent) with symptomatic perianal Crohn's disease treated by local operations were retrospectively reviewed to study outcome of local surgical intervention. RESULTS: All patients had intestinal disease that was limited to the colon in 32 patients (48 percent), ileocolonic region in 22 patients (33 percent), and ileum in 12 patients (18 percent). Types of perianal disease encountered included perianal suppuration (57), anal fistula (47), anal fissure (21), anal stenosis (5), gluteal abscess (3), scrotal abscess (2), and anovaginal fistula (2). A total of 321 episodes of anal complications necessitated 256 local surgical interventions. Local anorectal operations performed included simple incision and drainage of abscess (57), fistulotomy (35), incision and drainage of complex anorectal abscesses and fistulas and insertion of seton (24), internal sphincterotomy (6), fissurectomy (1), and anal dilation (3). Of 24 patients with horseshoe abscesses and fistulas managed with insertion of a seton and 35 patients who underwent fistulotomy as a primary procedure or in conjunction with drainage of an abscess, none experienced fecal incontinence as a direct result of the operation. Thirteen patients required proctectomy to control perianal disease, and a similar number underwent total proctocolectomy for extensive intestinal disease. Forty patients (61 percent) continue to retain a functional anus. CONCLUSION: Patients with symptomatic low anal fistula involving minimum sphincter musculature can be treated safely with fistulotomy. In treatment of patients with horseshoe abscesses and high fistulas, aggressive local surgical intervention using a seton permits preservation of the sphincter and good postoperative function.Poster presentation at the meeting of the American Gastroenterological Association, Digestive Disease Week, San Diego, California, May 14 to 17, 1995.     

Colonic Crohn's disease

The present review deals with the elective and emergency management of colonic Crohn's disease (CD). Failed medical therapy is among the most common indications for the operative treatment. In case of fistula the operation is usually a resection of the diseased segment of colon with wedge or segmental excision and closure of the secondarily involved organ. The incidence of Crohn's colonic stricture ranges from 5% to 17%. The main indication for performing a total colectomy and ileoproctostomy in patients with extensive Crohn's colitis is to avoid a permanent ileostomy and preserve rectal function. The authors performed 60 laparoscopic procedures: 35 ileocolic resections, 10 total colectomies, 10 loop ileosigmoidectomies, and 1 proctectomy. In conclusion, the choice of operation depends on many factors, such as the site and extent of disease. In some select instances a segmental resection of CD may afford better function than an ileoproctostomy. Received: 21 June 1999 / Accepted in revised form: 8 March 2000     

Duodenal Crohn's disease

Duodenal Crohn's disease is a rare condition not frequently encountered by the general or colo-rectal surgeon. Manifestations of Crohn's disease may appear in the duodenum as result of primary involvement, or secondary to complications of more distal gastrointestinal disease. Symptoms of duodenal Crohn's are often non-specific, and diagnosis can be difficult. This paper presents a summary of the published literature on duodenal Crohn's disease, including a review of the surgical approaches to this uncommon problem. Received: 6 November 2000 / Accepted: 16 January 2001     

The dilemma of Crohn's disease: Ileosigmoidal fistula complicating Crohn's disease

Summary Between 1965 and 1975, 27 patients underwent surgical treatment for ileosigmoidal fistulas complicating Crohn's disease at the Cleveland Clinic. There was no death and no anastomotic leak. The preferred procedure is resection of the ileocecal area involved by Crohn's disease with ileocolic anastomosis and a separate segmental resection of the sigmoid colon with colocolic anastomosis. A covering temporary loop ileostomy is used when there is associated pelvic sepsis or small-bowel obstruction.     

Perianal Crohn's disease

Various approaches to the management of perianal Crohn's Disease are discussed. In general, surgically, a conservative approach is taken because of the concern that wounds associated with the disease tend to heal poorly.     

Fistulizing Crohn's disease

Fistulas are common in Crohn's disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas.