Poor engagement and adherence predict neoplasia in inflammatory bowel disease: a case-control study

Background

Colorectal adenocarcinoma is an important and preventable complication of inflammatory bowel disease (IBD). A previous case series suggested mental health issues and poor engagement in care as novel risk factors.

Aims

To confirm the role of patient engagement in care in the development of neoplasia using a case-control methodology.

Methods

Patients in a single referral centre from 2007 to 2017 with colorectal adenocarcinoma, high-grade dysplasia or multifocal low-grade dysplasia were included as neoplasia cases. Each case was assigned up to three matched controls (matched for age, gender, underlying disease, IBD type and phenotype and disease duration). Novel and known risk factors were compared between groups.

Results

Thirty-two cases with 88 matched controls were included. Patients with neoplasia were more likely to have poor adherence to, or engagement with, care (odds ratio (OR) 4.79). They were also more likely to have chronic use of opioids (OR 3.86) and long-term prednisolone (OR 2.97). Of note, no difference was found in measures of socioeconomic disadvantage, reflecting equitable access to healthcare in the public institution where the care was studied. As previously shown, patients with neoplasia had multiple markers of increased cumulative burden of inflammation, including more IBD-related hospital admissions, elevated inflammatory markers and severe inflammation at colonoscopy.

Conclusions

This study confirms poor adherence or engagement with care as a new risk factor for colorectal adenocarcinoma in patients with IBD; identifying a vulnerable group whom clinicians should endeavour to engage in order to avoid this catastrophic complication.     

Dietary anthocyanins as a complementary medicinal approach for management of inflammatory bowel disease

Inflammatory bowel disease (IBD) is thought to result from a chronic or relapsing activation of the immune system in the GI tract. A growing body of evidence confirms the health benefits of dietary anthocyanins as plant-derived natural agents. The aim of this review is to provide an overview of several natural products rich in anthocyanins used worldwide for the treatment of IBD. Anthocyanins possess both protective and therapeutic functions in the management of IBD by alleviating oxidative stress processes, cytoprotective functions, downregulation of inflammatory cytokines and suppressing cellular signaling pathways of inflammatory processes. In conclusion, the consumption of anthocyanin-rich natural formulations must be promoted on the basis of their possible function in the prevention and treatment of gastrointestinal inflammatory disorders.     

A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a recurrent idiopathic inflammatory condition, characterized by disruption of the gut mucosal barrier. This mechanistic review aims to highlight the significance of plant-derived natural compounds as dietary supplements, which can be used in addition to restricted conventional options for the prevention of IBD and induction of remission. Various clinical trials confirmed the effectiveness and tolerability of natural supplements in patients with IBD. Mounting evidence suggests that these natural compounds perform their protective and therapeutic effect on IBD through numerous molecular mechanisms, including anti-inflammatory and immunoregulatory, anti-oxidative stress, modulation of intracellular signaling transduction pathways, as well as improving gut microbiota. In conclusion, natural products can be considered as dietary supplements with therapeutic potential for IBD, provided that their safety and efficacy is confirmed in future well-designed clinical trials with adequate sample size.     

Original research: Influence of comorbidities on treatment considerations for first-line biologic prescribing in patients with inflammatory bowel disease in the UK

BackgroundAnti-tumour necrosis factor (anti-TNF) therapies are the most commonly used biologics for inflammatory bowel disease (IBD), but for patients with a comorbidity, newer agents may be a more appropriate treatment choice.AimsTo investigate the impact of comorbidities in patients with IBD, on first-line biologic prescribing habits of IBD-specialist healthcare practitioners in the UK.MethodsIBD-specialist physicians and nurses were asked to answer an online survey, considering different prescribing scenarios in ulcerative colitis (UC) and Crohn’s disease (CD). Respondents could indicate a preference for anti-TNFs or newer biologics, both in the absence and presence of 10 common comorbidities.ResultsA total of 120 IBD-specialist healthcare professionals (HCPs) completed the survey. In the absence of comorbidities, anti-TNFs were favoured; infliximab was the preferred first-line biologic in both UC and CD (43% and 37% of respondents, respectively). On introducing comorbidities, the largest shift in prescribing behaviour was for vedolizumab, with preference increasing by 27% and 21%, compared with infliximab, which fell by 14% and 9% in UC and CD, respectively. Chronic/recurring infection (46%), congestive heart failure (≤44%) and malignancies (≤43%) were the most commonly selected comorbidities for vedolizumab treatment.ConclusionsClinicians adapt their biologic prescribing habits in patients with IBD with comorbidities, considering known contraindications and precautions. A preference for vedolizumab is evident in many cases, however, for several comorbid scenarios, including demyelinating disorders, chronic obstructive pulmonary disease and malignancy, anti-TNFs are prescribed despite known risks. It is important that continual re-evaluation of the IBD treatment landscape is undertaken by HCPs, in alignment with recommendations in published guidelines.     

Osteoprotegerin: A novel biomarker for inflammatory bowel disease and gastrointestinal carcinoma

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily of proteins. Although initial data illustrated the key role that OPG plays in bone turnover, numerous recent reports indicate that OPG is also an important factor in inflammatory pathways and tumor cell survival. OPG contributes directly to inflammatory processes and has been evaluated as a novel non‐invasive biomarker of gut inflammation. Furthermore, OPG affects cell turn‐over, differentiation, death, and survival via extracellular pathways, correlating with worse prognosis in inflammatory bowel diseases and several gastrointestinal carcinomas. It is now clear that OPG has multiple functions and characteristics. This review gives an overview of OPG, highlights its roles in different extracellular pathways, and outlines how OPG could be used as a novel non‐invasive biological marker in inflammatory bowel diseases and gastrointestinal carcinomas.     

Toxicity and response to thiopurines in patients with inflammatory bowel disease

The use of thiopurines is well established in the management of inflammatory bowel disease. A wealth of data and experience, amassed over several decades, supporting their efficacy has recently been challenged by trials that failed to show a benefit in Crohn’s disease when used early in the disease course, although other trials continue to support their role both as monotherapy and in combination with anti-TNF. Recent reports of previously unrecognized toxicity have also emerged. Fortunately, the absolute incidence of serious toxicity remains low, and an improved understanding of how best to minimize risk and the recognition of groups of patients at higher risk of toxicity from thiopurines means that they remain a relatively safe therapy in the majority of patients. In this paper, we review the literature evaluating the role of thiopurines in inflammatory bowel disease as well as their toxicity. We conclude that education regarding the spectrum of thiopurine side effects and optimal monitoring during therapy may help with optimizing safety and efficacy of these important medications.     

Relationship between methylation and colonic inflammation in inflammatory bowel disease

AIM:To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients.METHODS:We evaluated the methylation status of 2genes(SLIT2 and TGFB2)in 226 biopsies taken from62 colonoscopies of 38 patients(29 ulcerative colitis and 9 Crohn’s colitis)using methylation-specific melting curve analysis.The relationships between methylation status and clinical,biological,endoscopic and histological activities were evaluated.Twenty-three of the 38patients had a second colonoscopy and were included in a longitudinal analysis.Numerical results were given as the means±SD of the sample and range,except when specified.Student t analysis,U Mann Whitney and ANOVA factor were used to compare the means.Qualitative results were based on theχ2 test.RESULTS:SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission(55%vs 18%,P<0.001).SLIT2 methylation was also higher in samples with acute inflammation(56.5%)than in samples with chronic(24%)or absent inflammation(15%)(P<0.001).For TGFB2methylation,the correlation was only significant with endoscopic activity.Methylation was higher in the distal colon for both genes(P<0.001 for SLIT2 and P=0.022for TGFB2).In the multivariate analysis,only inflammation status(and not disease duration or extension)was independently associated with SLIT2 methylation[OR=6.6(95%CI:1.65-27.36),P=0.009].In the longitudinal analysis,the maintenance of endoscopic remission was protective for methylation.CONCLUSION:Endoscopic and histological inflammation are predictive for SLIT2 methylation.     

Specificities of the intestinal microbiota in patients with inflammatory bowel disease and Clostridium difficile infection

Clostridium difficile infection (CDI) is a common complication in inflammatory bowel disease (IBD) and has been associated with poor IBD outcome. Intestinal microbiota composition in IBD patients with CDI has not been specifically evaluated to date. The fecal microbiota of 56 IBD patients, including 8 in flare with concomitant CDI, 24 in flare without CDI, and 24 in remission, as well as 24 healthy subjects, was studied using 16S sequencing. Analysis was performed using the Qiime pipeline. Compared to IBD patients without CDI, IBD patients with CDI had more pronounced dysbiosis with higher levels of Ruminococcus gnavus and Enterococcus operational taxonomic units (OTUs) and lower levels of Blautia and Dorea OTUs. Correlation network analysis suggested a disrupted ecosystem in IBD patients in flare, particularly in those with CDI. In patients with IBD, CDI is associated with a more pronounced intestinal dysbiosis with specific alterations in intestinal microorganisms.     

Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease

Background: There may be an increased risk of colorectal cancer after cholecystectomy, but the literature is not consistent. It is also possible that any risk might be associated with gallstones rather than cholecystectomy. Methods: In a prospective necropsy study of 8563 cases, all 219 cases of a previous cholecystectomy were pair-matched to subjects with gallstones and to subjects with a normal gallbladder. In a second study all 192 cases of colorectal cancers were pair-matched to cancer-free subjects. Results: The odds ratio (OR) for developing colorectal cancer after cholecystectomy compared with a normal gallbladder was 1.0 (95% confidence interval, 0.30-3.34) and with unoperated gallstones was 0.88 (0.27-2.76). Conclusions: This study fails to support an association between cholecystectomy or gallstones and colorectal cancer. For those cases of colorectal cancer versus controls, the OR for previous cholecystectomy was 0.70 (0.23-2.04) and for gallstone disease was 0.93 (0.58-1.48).     

High and low body mass index may predict severe disease course in children with inflammatory bowel disease

Objectives: Inflammatory bowel disease (IBD) has been historically associated with underweight and malnutrition. The impact of both underweight and obesity on the clinical course of IBD in adults is controversial. This study described the association between body mass index (BMI) at diagnosis to disease course in children with IBD.

Methods: We reviewed the medical records of children with IBD from the database of the ‘Dana-Dwek’ Children’s Hospital between 2010 and 2016. Demographic and anthropometric data were collected as were disease characteristics, course and therapy. Patients were categorized in quartiles according to BMI percentiles at diagnosis (Q1–Q4).

Results: Of 100 children who were identified, 62 had Crohn’s disease (CD) and 38 had ulcerative colitis (UC). The median age (interquartile range, IQR) at diagnosis was 13.7 (range 11.9–15.2) years. The median (IQR) follow-up was 2.1 (1.2–3.8) years. At diagnosis, 46 children (46%) were in Q1, 20 (20%) in Q2, 19 (19%) in Q3 and 15 (15%) in Q4. Prolonged time to diagnosis was associated with BMI in Q1 and Q4, as well as high disease activity at diagnosis (p?p?=?.016) and anti-tumor necrosis factor (TNF) therapy (HR 4.489 and 3.972, respectively, p?=?.021).

Conclusions: BMI in the lower and upper quartiles was associated with more severe disease course in children with IBD. BMI may serve as a simple and highly accessible predictor of pediatric IBD course and prognosis.     

Who and how to screen for cancer in at-risk inflammatory bowel disease patients

Inflammatory bowel diseases (IBDs) include both Crohn’s disease and ulcerative colitis and both diseases are marked by inflammation within the gastrointestinal tract. Due to long-standing inflammation, IBD patients are at increased risk of colorectal cancer, especially patients with chronic inflammation, pancolitis, co-diagnosis of primary sclerosing cholangitis and a longer duration of disease. Small bowel inflammation places Crohn’s patients at an increased risk of small bowel cancer. A higher risk of skin cancers, lymphomas and cervical abnormalities is also seen in IBD patients; this is likely related to both disease factors and the presence of immunosuppressive medication. This article reviews which patients are at an increased risk of IBD-associated or IBD treatment-associated cancers, when to begin screening and which screening methods are recommended.     

Motivational interviewing in inflammatory bowel disease patients: A useful tool for outpatient counselling

Background

Most inflammatory bowel disease patients miss follow-up visits and are non-adherent to therapy due to the lack of an engaging patient–physician relationship. Motivational interviewing is a patient-centred counselling method used to elicit/strengthen motivation towards change. The aim of this study was to assess the role of motivational interviewing in patients affected by inflammatory bowel disease.

Methods

The study included consecutive patients with inflammatory bowel disease presenting for the first consultation (June 2012–February 2013). All consultations were carried out applying the motivational interviewing approach. After each consultation, patients filled out a questionnaire asking demographic data, and their past and current experience.

Results

Overall, 23 males (51.1%) and 22 females (48.9%), mean age 36.1 ± 15.2 years, were enrolled. Before and after experiencing the motivational interviewing approach (mean visit duration 41.5 ± 8.7 min) “overall satisfaction rate”, “physician's communication skills”, and “perceived empathy” were 60% vs 100%, 40% vs 95.6%, and 40% vs 100%, respectively. Satisfaction was lower in patients affected by indeterminate colitis (p = 0.004), and of younger age (p = 0.02).

Conclusion

The motivational interview approach is appreciated by inflammatory bowel disease patients. Despite being time-consuming, the motivational interview appears considerably worthwhile at the first visit and in younger patients. Motivational interviewing can help physicians to deal with their patients, moving from “cure” to “care”.     

5-ASA在炎症性肠病相关结直肠癌中的化学预防作用

癌变是溃疡性结肠炎(ulcerative colitis,UC)最严重的并发症,其预防手段包括内镜监测、分子生物标志物、手术治疗及化学预防。5-氨基水杨酸盐(5-aminosalicylic acid,5-ASA)是轻-中度UC患者的一线用药,其对炎症性肠病(inflammatory bowel disease,IBD)相关结直肠癌的化学预防作用及机制尚不十分明确。本文较全面地阐述5-ASA的化学预防作用及机制研究进展,旨在为临床实践中预防IBD相关癌变用药方案提供更多依据。