Prevention and treatment of postoperative recurrence of Krohn's disease

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Crohn's disease (Crohn's disease CD) is a chronic recurrent gastrointestinal inflammatory disease, despite the use of drugs in clinic, such


Crohn's disease (Crohn's disease CD) is a chronic recurrent gastrointestinal inflammatory disease, despite the use of drugs in clinic, such as 5- aminosalicylic acid (5-ASA), corticosteroids, immunosuppressive agents, and biological agents (such as anti-tumor necrosis factor monoclonal antibody, infliximab) treatment, the operation rate is still high. Foreign reports have 50%-80% CD patients need surgery, especially in patients with severe complications (such as fistula, stenosis, abscess, perforation) and medical treatment is invalid, the majority of recurrence after surgical treatment, surgical treatment again. Due to the lack of attention to patients and doctors, the operation rate is not high. In the literature, 1 years after endoscopic surgery, 28%-73% was found to be associated with recurrence of intestinal mucosal inflammation in patients with. Therefore, it is especially important to prevent recurrence and clinical treatment.

Postoperative recurrence of CD includes clinical, endoscopic, histological and imaging findings. Clinical relapse mainly refers to the recurrence of clinical symptoms, abdominal pain, diarrhea, as well as the impact of daily life, CD activity index (CDAI) > 200. Histological recurrence mainly refers to the inflammatory changes in the intestinal mucosa tissue, the presence of structural changes in the glands, intestinal epithelial cells proliferation, necrosis or fall off, white blood cell infiltration and ulceration, etc.. Endoscopic recurrence mainly refers to in the absence of clinical, endoscopic findings and anastomosis of proximal bowel mucosal inflammation, usually in postoperative endoscopy diagnosed in June.

Mechanism and inducement of postoperative recurrence

The mechanism of postoperative recurrence is still unclear, and it is found that bacterial antigen is an important motivating factor. Rutgeerts found that ileal resection combined with enterostomy to defecate by ileo colonic anastomosis, anastomotic and ileal mucosal inflammation will not relapse; however, if the stool to continue through mucosal inflammation after anastomotic recurrence, and the recurrence of anastomotic site in the end of the small intestine. It was found that the proximal intestinal mucosa of anastomotic stoma was associated with recurrence after operation. The main causes of recurrence after CD were as follows: 1) smoking, smoking significantly increased postoperative recurrence, for a large number of smokers (³ 15 /d) recurrence rate was higher. Studies have shown that 5 years after the recurrence rate of smokers was 36%, while non-smokers were only about $20%. 2) disease related factors: patient age, duration of disease, is associated with the stricture and penetrating like inflammation, extent of disease, severity, ileum colon anastomosis, especially penetrating lesions (perforation, abscess, fistula). 3) surgery related factors: end to side anastomosis and anastomosis than end end anastomosis and the extent of surgery, complications and whether mucosa non caseous granuloma and blood transfusion and so on. Another study found that bleeding, obstruction, and postoperative anastomotic leakage was associated with recurrence, but some scholars do not support. In conclusion, smoking and perforation are the most important factors for postoperative recurrence.

Two, the diagnosis of postoperative recurrence

At present, endoscopic, histopathological and imaging examinations are often used to determine the recurrence of CD, but these results are still different from the occurrence of the disease. The markers, such as CRP, anti neutrophil cytoplasmic antibody (pANCA) and anti Saccharomyces cerevisiae antibody (ASCA) and calcium binding protein or fecal lactoferrin clinical value. Rutgeerts proposed by endoscopy, according to endoscopic anastomotic stoma or upper intestinal mucosal inflammation grade judgment of postoperative recurrence. For the specific I-0 level: normal mucosa inflammation, inflammation and ulcer; I-1: less than 5 ulcer; I-2: > 5 ulcer, ulcer between the normal mucosa; I-3; intestinal (small) scattered in aphthous ulcers and mucosal inflammation lesions; I-4: diffuse mucosal inflammation with large ulcers, nodular hyperplasia or inflammatory bowel stenosis. Clinical observation of endoscopic mucosal grade I-0 or I-1, 80%-85% patients 3 years without recurrence, the recurrence rate of < 5%; and I-2 and I-3 in mucosal inflammation grading, I-4, within 3 years of clinical symptoms and the recurrence rate were 15%, 40% and 90%. Endoscopic mucosal inflammation was preceded by recurrence of clinical symptoms, mucosal inflammation in patients with grade I-2 showed an exacerbation of disease; I-3 and I-4 class suggested a critical condition, poor prognosis. Therefore, endoscopic examination revealed that the more severe mucosal inflammation, the more severe the disease, usually with endoscopic mucosal inflammation grade ³ I-2 level that CD recurrence. Based on the importance of endoscopy, endoscopic examination was performed in June. Colonoscopy and small bowel endoscopy are superior and can be used to analyze the intestinal mucosa. Capsule endoscopy can also be used to observe mucosal edema, ulcer and stenosis, which is more suitable for the high inflammatory lesions in the upper ileum.

Three, the treatment of postoperative recurrence

The current clinical treatment of postoperative recurrence of CD is still not standardized treatment guidelines, except in the preoperative nutritional support therapy, perioperative treatment, gastrointestinal medicine and surgery experts should together medical discussions to make reasonable surgical plan according to the patient's condition, postoperative patients should be entrusted to give up smoking, enhanced nutritional support therapy.

1.5-ASA 5-ASA: the use of drugs to reduce CD prophylactic postoperative recurrence remains controversial, found after oral administration of 5-ASA can reduce the CD postoperative recurrence rate and intestinal mucosal inflammation degree of previous clinical analysis, but the bulk of cases from Italy clinical meta-analysis found that endoscopic 5-ASA can only reduce the recurrence of 18% patients. Based on the limited role of 5-ASA, there is no need for preventive treatment for asymptomatic patients with low risk. The European IBD consensus guidelines recommend that > 2g/d's preventive treatment of 5-ASA can reduce postoperative recurrence of CD.

2 glucocorticoid: clinical studies have shown that glucocorticoids may be effective in some patients, can alleviate the proximal anastomosis and mucosal inflammation, but because of the long-term use is accompanied by serious side effects, clinical efficacy remains to be seen, but is ineffective in preventing the recurrence of CD after operation.

3 antibiotics: the literature reported that the use of metronidazole (mg/kg/d) within 7 days after surgery began in March, significantly reducing the recurrence of CD after endoscopic surgery. Other studies found that the clinical recurrence rate of CD was significantly lower after 1 years of treatment with Ornidazole (1g/d). Despite the use of these drugs to reduce the clinical recurrence of CD, but due to long-term use of serious complications, clinical application is limited.

4: immunosuppressant azathioprine /6- mercaptopurine (AZA/6-MP) can effectively treat CD, symptom control, maintenance of remission, and can effectively control the postoperative recurrence of CD. The use of AZA to 2-4 weeks after operation (2-2.5 mg/kg) treatment, colonoscopy after March found endoscopic recurrence rate was 34.3%, while the control group was 52.6%; 1 years after treatment, colonoscopy found endoscopic recurrence was 43.7%, and 69% in the control group, and AZA treatment after endoscopic mucosal inflammation grade significantly reduce. Clinical study found that after 5 years of long-term maintenance of AZA for more than 3 years, the survival rate was significantly prolonged. While methotrexate (MTX) in the clinical treatment of recurrence after CD reported little.

Although the study found that: 5 probiotic bacteria in fecal antigen in the postoperative recurrence of CD plays an important role, and the postoperative recurrence in higher bacterial concentrations of anastomotic and proximal small bowel region, but clinical studies showed that probiotics treatment is still not sure about the effect of CD recurrence.

6 biological immunotherapy: recent reports using infliximab in 2-4 weeks after operation after intravenous treatment (5 mg/kg), zeroth, 2, 6 weeks each time, and then use an interval of 8 weeks, found that mucosal inflammation recurrence rate was 9.1% after 1 years of endoscopic observation, significantly lower than the control group 84.6%, endoscopic mucosal inflammation grading is significantly reduced; histopathological examination revealed inflammation recurrence rate was 27%, significantly lower than the control group 85%; and the clinical remission rate was 90.9%, 15.4% higher than the control group; CDAI integral is also at a low level. Therefore, anti TNF monoclonal antibody plays an important role in the control of clinical symptoms, maintenance of remission and prevention of postoperative recurrence in patients with CD.

Four, CD postoperative clinical treatment plan

The first surgical treatment, if only for the stricture, no smoking in low-risk patients, no general postoperative need drug treatment, after 6-12 months of colonoscopy, if found no recurrence of inflammation, annual follow-up endoscopic examination, without treatment. The smoking history, with intestinal perforation, lesions involving the colon, ileum resection of high-risk patients with > 10 cm, 5-ASA after operation (3-4 g/d) in prophylactic treatment after 6-12 months of colonoscopy, if there is no recurrence of inflammation, annual follow-up endoscopic examination, without treatment; if it is found that the intestinal mucosal inflammation recurrence then, oral AZA (2.0-2.5 mg/kg/d) or 6-MP (1.0-1.5 mg/kg/d) long-term maintenance treatment, follow-up colonoscopy every year. Reoperative treatment for patients, advice, use AZA (2.0-2.5 mg/kg/d) or 6-MP (1.0-1.5 mg/kg/d) 6-12 months of treatment, recurrence of colonoscopy, without recurrence, continue treatment, annual colonoscopy follow-up; if endoscopic recurrence, recommend the use of infliximab treatment.

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