ABSTRACT
Background: Some of the active perianal fistulizing Crohn's disease (CD) patients achieving remission with infliximab (IFX) therapy would develop relapse of perianal fistula within weeks to years after discontinuation of IFX therapy. Aims: To assess the outcomes of patients with perianal fistulizing CD after discontinuation of IFX therapy and the risk factors for relapse of perianal fistula. Methods: The clinical data of patients with perianal fistulizing CD who received IFX therapy at Shanghai Renji Hospital between June 2013 and May 2019 and stopped IFX therapy after achieving complete or partial radiological remission were collected retrospectively and analyzed. Demographic data, clinical and imaging characteristics, as well as data of IFX treatment and relapse of perianal fistula were extracted. Kaplan-Meier analysis was performed to calculate the cumulative probabilities of perianal and luminal relapse, while Cox proportional hazards model was applied to identify the risk factors for relapse. Results: A total of 56 perianal fistulizing CD patients who had been treated with IFX and stopped IFX therapy were included. Of them 26 achieved complete radiological remission and 30 achieved partial radiological remission. The median follow-up time was 20.5 months. Twenty-one patients (37.5%) had relapse of perianal fistula. The cumulative probabilities of perianal relapse were 29.0%, 33.7% and 42.8% at 12, 24 and 60 months after IFX discontinuation, respectively; and the cumulative probabilities of luminal relapse were 21.7%, 31.2% and 56.4% at 12, 24 and 60 months after IFX discontinuation, respectively. Multivariate analysis showed that non-stricturing and non-penetrating type (HR=9.711, 95% CI: 1.210-77.939, P=0.032) and involvement of rectum (HR=3.034, 95% CI: 1.119-8.231, P=0.029) were independent risk factors for relapse of perianal fistula, while the frequency of using of IFX therapy was a protective factor (HR=0.885, 95% CI: 0.792-0.990, P=0.032). Conclusions: There is a high risk of relapse of perianal fistulizing CD after discontinuation of IFX therapy. Non-stricturing and non-penetrating type and rectal involvement are risk factors for relapse of perianal fistula, and increasing the frequencies of using IFX therapy is crucial for the maintenance of remission.
ABSTRACT
Perianal fistulizing Crohn's disease (pfCD)often indicates aggressive and refractory phenotype. Two-thirds of the patients with pfCD will relapse,so the treatment is really challenging. Currently,biological agents have made great progress. The application of biological agents such as infliximab brings new hope to the treatment of pfCD. This article reviewed the application of biological agents in treatment of pfCD.
ABSTRACT
DNA copy number variation is an important pathogenic factor of human diseases and might be involved in the pathogenesis and pathological process of inflammatory bowel disease (IBD).Aims: To investigate the copy number variation of CNTNAP3 gene and its significance in Crohn''s disease (CD).Methods: A total of 101 active CD patients admitted from Jul.2009 to Dec.2010 at Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled.Eighty healthy subjects were served as controls.Peripheral blood or intestinal mucosa samples of CD patients were collected, and the copy number variation of CNTNAP3 gene was screened and validated by array-based comparative genomic hybridization (aCGH, n=8) and real-time PCR (n=93);expression of CNTNAP3 encoding protein was determined by ELISA (n=55).Results: A large fragment copy number amplification was revealed by aCGH at chromosome 9p13 region (including CNTNAP3 gene) in untreated CD patients.Real-time PCR confirmed that the copy number of CNTNAP3 gene was amplified in peripheral blood of CD patients, especially steroid-naive patients as compared with the normal controls (208 616.4±126 984.7 and 233 453.3±113 520.8 vs.161 750.2 ±53 940.3, P0.05).Furthermore, the plasma CNTNAP3 level in CD patients with amplified copy number was not correlated with the simplified endoscopic score for CD (P>0.05).Conclusions: Copy number amplification of CNTNAP3 gene might be involved in the pathogenesis of CD in Chinese population.Glucocorticoid treatment and smoking might affect the copy number variation of CNTNAP3 gene.Plasma CNTNAP3 level cannot discriminate CD patients from healthy subjects.Conclusions of this study needs to be further demonstrated and discussed.
ABSTRACT
Objective To explore the role of a novel regulatory molecule-microRNA in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT in order to provide a new reversal target for muhidrug resistance.Methods MicroRNA expression profiling in the hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT were detected by microRNA array using microRCURYTM LNA Array V8.1 to screen multi-drug resistance(MDR)-related microRNAs.Specific stem-loop primers were used for reverse-transcribing cDNA and the expression of some MDR-related microRNAs were analyzed by the real-time PCR.Results The absorbance ratios of total RNA used for total RNA preparation was further confirmed by denaturing agarose gel electrophoresis.Compared to SW1116,28 microRNAs were down-regulated and 36 microRNAs were up-regulated in SW1116/HCPT cell line.The expression of two down-regulated microRNAs(hsa-miR-452 and hsa-miR-373*)and one up-regulated microRNA(hsa-miR-506)were confirmed by real-time PCR.The results of hsa-miR-452 and hsa-miR-506 were consistent with microRNA array nalysis,however,the expression of hsa-miR-373* may play a key role in the process of hydroxycamptothecin-resistant human colon cancer cell line SW1116/HCPT.