Indications for 5-aminosalicylate in inflammatory bowel disease:Is the body of evidence complete?

Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and con- comitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related co- lonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dos- age to improve compliance. Therefore, due to its supe- rior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, pae- diatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.

Lymphogranuloma venereum proctosigmoiditis is a mimicker of inflammatory bowel disease

There has been an increasing prevalence of lymphogranuloma venereum(LGV) or Chlamydia trachomatis(C.trachomatis) cases among the men who have sex with men(MSM) population,particularly in Europe and North America.These cases may present with an incomplete or undisclosed history and proctosigmoiditis without characteristic adenopathy syndrome.During the initial evaluation and colonoscopy,there is a strong clinical and endoscopic suspicion of inflammatory bowel disease(IBD) by virtue of presentation and endoscopic and histological findings.The diagnosis of IBD is subsequently modified to LGV proctosigmoiditis when one or more of the following transpire:(1) there is failure of response to IBD therapy;(2) additional components of history(MSM/travel) may be identified;(3) return of initially performed Chlamydia antibody test is positive;and(4) response to antibiotics effective against Chlamydia.We describe three such cases initially suspectedto be an inflammatory bowel disease and subsequently identified as C.trachomatis proctosigmoiditis.

IC5, a dithiocarbamate derivative, inhibits colon cancer cell proliferation in vitro and colitis-associated colorectal carcinogenesis in vivo

Colorectal cancer （CRC） is one of the leading causes of cancer-related deaths, and inflammatory bowel diseases and dysregulated cell proliferation play important roles in colorectal carcinogenesis. Therefore, inhibition of inflammatory signaling and cell proliferation is used as a major strategy for chemoprevention of CRC. In the present study, it was found that IC5, a dithiocarbamate derivative, could inhibit the proliferation of LoVo human colon cancer cells in a concentration-dependent manner, with an IC50 of 22 gM. The anti-proliferation effect of IC5 was accompanied by a significant cell cycle arrest in G2/M phase. Further study revealed that IC5 significantly inhibited NF-~B signaling in LoVo cells, suggesting that IC5 could inhibit inflammatory responses. We then evaluated the in vivo efficacy of IC5 to inhibit colitis-associated colorectal carcinogenesis using an azoxymethane （AOM）/dextran sodium sulfate （DSS） mouse model. AOM/DSS treatment resulted in a CRC incidence of 58.3%, while the incidences were decreased to 37.5% and 25% in mice orally administered with 50 and 100 mg/kg IC5, respectively. In addition, IC5 also reduced the plasma levels of alanine aminotransferase and asparatate aminotransferase. Taken together, these results suggested that IC5 could prevent colitis-associated colorectal carcinogenesis, and more attention should be paid to it as a cancer chemopreventive agent in further investigation.

Pathogenesis of Inflammatory Bowel Disease and the Action Mechanism of Moxibustion

To organize the researches on the pathogenesis of inflammatory bowel disease （IBD） and the reports of moxibustion for IBD in recent years, for summarizing the current status of the pathogenesis study on IBD and the mechanism research on moxibustion for IBD, and giving suggestion to the further study on the action of moxibustion in managing this disease.

High-risk human papilloma virus infection and cervical neoplasm in female inflammatory bowel disease patients:a cross-sectional study

Background and aim:This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus(HPV)infection,especially types 16 and 18,and cervical neoplasia in female Inflammatory bowel disease(IBD)patients.Methods:From July 2014 to January 2017,sexually active,female,Chinese IBD patients(21–60 years)and age-matched controls underwent cervical ThinPrep cytology testing(TCT)and high-risk HPV-DNA detection,and completed questionnaires about awareness of cervical cancer and HPV.Cervical dysplasia was categorized as cervical intraepithelial neoplasia(CIN)1,2 and 3.Results:Of 124 IBD patients(30 ulcerative colitis and 94 Crohn’s disease),17(13.7%)had high-risk HPV among whom 9(7.3%)had HPV 16/18 infection and 4(3.2%)had cervical CIN(3 CIN 3,1 CIN 1)by pathology.Among 372 controls,33(8.9%)had high-risk HPV and only 1(0.3%)had HPV 16 infection.Cervical TCT detected atypical squamous cells of unknown significance in one control;no control had CIN.The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls(both P<0.001).The HPV-infection rate was higher in patients administered methotrexate[P=0.005,odds ratio(95%confidence interval)4.76(1.471–15.402)]or more than two immunosuppressants[P=0.013,odds ratio(95%confidence interval)3.64(1.255–10.562)].Thiopurine,steroid,infliximab and disease behavior/location were not associated with HPV infection.Only 29.3%of patients had undergone cervical-cancer screening.Awareness of HPV infection and HPVrelated cervical cancer was poor(28.2%).Conclusions:Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia,which may be associated with immunosuppressants.Education and routine follow-up with HPV-DNA testing and TCT are recommended,especially in female Chinese IBD patients.

Colorectal cancer resection rates in patients with inflammatory bowel disease:a population-based study

Background and objective:Inflammatory bowel disease(IBD)is associated with an increased risk of colorectal cancer(CRC).This study aimed to analyse the trends in rates of resection for IBD-related CRC in the USA.Methods:We used the Nationwide Inpatient Sample from 1995 to 2012.Temporal trends in age-adjusted rates of resection for CRC in the setting of IBD were analysed using multivariate Joinpoint regression models.The primary outcome was surgical resection of CRC in the setting of IBD.Results:We included 3597168 IBD discharges in the present study,of which 275479 underwent CRC resection between 1995 and 2012.The annual CRC resection rates among IBD population decreased significantly from 1995 to 2012.This decrease was significant in all age groups with an annual decrease of 393(P<0.001),359(P<0.001),293(P<0.001)and 159(P<0.001)per 100000 IBD discharges between 1995 and 2012 for age groups 18–39,40–49,50–74 and>75 years,respectively.The annual IBD-CRC resection rate per 100000 IBD discharges for proximal CRC decreased by 149(P<0.001),130(P<0.001),95(P<0.001)and 50(P<0.001),respectively,and the annual distal CRC resections per 100000 IBD discharges decreased by 104(P<0.001),123(P<0.001),123(P<0.001)and 82(P<0.001),respectively,for age groups 18–39,40–49,50–74 and>75 years,between 1995 and 2012.On multivariate Poisson regression analysis,after adjustment for age and sex,CRC resections decreased by 3.9%each year from 1995 to 2012.Conclusions:CRC resection rates among IBD patients have continued to decrease annually from 1995 to 2012.There is a population-level decrease in resection of both proximal and distal CRC reflecting a decreasing incidence of IBD-related CRC incidence in the USA.

Vedolizumab use in patients with inflammatory bowel diseases undergoing surgery:clinical trials and post-marketing experience

Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.