Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps.

BACKGROUND: Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. METHODS: High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. RESULTS: Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. CONCLUSION: Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

Endoscopic Resections in Inflammatory Bowel Disease: A Multicentre European Outcomes Study.

BACKGROUND AND AIMS: Inflammatory bowel disease is associated with an increased risk of colorectal cancer, with estimates ranging 2-18%, depending on the duration of colitis. The management of neoplasia in colitis remains controversial. Current guidelines recommend endoscopic resection if the lesion is clearly visible with distinct margins. Colectomy is recommended if complete endoscopic resection is not guaranteed. We aimed to assess the outcomes of all neoplastic endoscopic resections in inflammatory bowel disease. METHODS: This was a multicentre retrospective cohort study of 119 lesions of visible dysplasia in 93 patients, resected endoscopically in inflammatory bowel disease. RESULTS: A total of 6/65 [9.2%] lesions <20 mm in size were treated by ESD [endoscopic submucosal dissection] compared with 59/65 [90.8%] lesions <20 mm treated by EMR [endoscopic mucosal resection]; 16/51 [31.4%] lesions >20 mm in size were treated by EMR vs 35/51 [68.6%] by ESD. Almost all patients [97%] without fibrosis were treated by EMR, and patients with fibrosis were treated by ESD [87%], p < 0.001. In all, 49/78 [63%] lesions treated by EMR were resected en-bloc and 27/41 [65.9%] of the ESD/KAR [knife-assisted resection] cases were resected en-bloc, compared with 15/41 [36.6%] resected piecemeal. Seven recurrences occurred in the cohort. Seven complications occurred in the cohort; six were managed endoscopically and one patient with a delayed perforation underwent surgery. CONCLUSIONS: Larger lesions with fibrosis are best treated by ESD, whereas smaller lesions without fibrosis are best managed by EMR. Both EMR and ESD are feasible in the management of endoscopic resections in colitis.

Depressive symptoms in inflammatory bowel disease: an extraintestinal manifestation of inflammation?

Depressive symptoms are reported by more than 20% of people with inflammatory bowel disease (IBD), while sleep difficulties and fatigue are even more common. Co-morbid depressive symptoms predict a poor IBD course, including increased risk of relapse and surgery, which is inconsistently improved by psychological treatments. Rather than being distinct systems, there is compelling evidence for bidirectional communication between gut and brain, driven by neural, metabolic, endocrine and inflammatory mediators. An emerging concept is that depressive symptoms may be mechanistically linked to excess inflammation and dysregulation of the gut-brain axis. Given the close link between the intestinal microbiota and host immune responses, patients prone to shifts in their intestinal microbiome, including smokers, those with poor diet and early life stress, may be exposed to exaggerated immune responses. Excess inflammation is associated with brain changes (depressive symptoms, fatigue, sleep difficulties) and worsening gastrointestinal symptoms, which are exacerbated by psychological distress. Equally, treatments both for depressive symptoms and IBD provide opportunities to break this cycle by reducing the causes and effects of inflammation. As well as addressing potential risk factors such as smoking and diet, treatments to alter the microbiome may reduce depressive symptoms. Observational evidence suggests that anti-inflammatory treatments for IBD may improve co-morbid depressive symptoms correlating with reduction in inflammation. With a growing range of treatments targeting inflammation centrally, peripherally and in the gut, IBD provides a unique model to understand the interplay between brain and gut in the pathogenesis of depressive symptoms, both in IBD and in the whole population.

A multi-centre audit of excess steroid use in 1176 patients with inflammatory bowel disease.

BACKGROUND: Corticosteroids are central to inducing remission in inflammatory bowel disease (IBD) but are ineffective maintenance agents. AIM: To benchmark steroid usage in British outpatients and assess factors associated with excess exposure. METHODS: We recorded steroid use in unselected IBD outpatients. Cases meeting criteria for steroid dependency or excess were blind peer reviewed to determine whether steroid prescriptions were avoidable. Associations between steroid use and patient/institutional factors were analysed. RESULTS: Of 1176 patients, 30% received steroids in the prior 12 months. 14.9% had steroid dependency or excess, which was more common in moderate/severe ulcerative colitis (UC) than Crohn's disease (CD) (42.6% vs 28.1%; P = .027). Steroid dependency or excess was deemed avoidable in 49.1%. The annual incidence of inappropriate steroid excess was 7.1%. Mixed-effects logistic regression analysis revealed independent predictors of inappropriate steroid excess. The odds ratio (OR, 95%CI) for moderate/severe compared to mild/quiescent disease activity was 4.59 (1.53-20.64) for UC and 4.60 (2.21-12.00) for CD. In CD, lower rates of inappropriate steroid excess were found in centres with an IBD multi-disciplinary team (OR 0.62 [0.46-0.91]), whilst dedicated IBD clinics protected against inappropriate steroid excess in UC (OR 0.64, 95% CI 0.21-0.94). The total number of GI trainees was associated with rates of inappropriate steroid excess. CONCLUSIONS: Steroid dependency or excess occurred in 14.9% of British IBD patients (in 7.1% potentially avoidable). We demonstrated positive effects of service configurations (IBD multi-disciplinary team, dedicated IBD clinics). Routine recording of steroid dependency or excess is feasible and should be considered a quality metric.

Safety of Anti-TNF Treatment in Liver Transplant Recipients: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Little is known about the risk of serious infection when combining anti-tumour necrosis factor [TNF] therapy for refractory inflammatory bowel disease [IBD] with immunosuppression after liver transplantation [LT]. Our aim was to investigate the infection risk in this patient group by systematic review and meta-analysis of the available data. METHODS: A search was conducted for full papers and conference proceedings through September 2015, regarding liver transplant recipients and anti-TNF therapy. All studies were appraised using the adapted Newcastle-Ottawa Scale [NOS]. Two reviewers independently extracted patient data [age, duration of follow-up, number of all infections, number of serious infections, time since transplant]. As an additional control population, primary sclerosing cholangitis [PSC]-IBD patients from the Leiden University Medical Center [LUMC] LT cohort were used. Poisson regression was used to compare serious infections (according to International Conference on Harmonisation [ICH] definition) per patien-year follow-up between the anti-TNF and control groups. RESULTS: In all 465 articles and abstracts were identified, of which eight were included. These contained 53 post-LT patients on anti-TNF therapy and 23 post-LT patients not exposed to anti-TNF therapy. From the LUMC LT-cohort, 41 PSC patients with PSC-IBD not exposed to anti-TNF therapy were included as control population. The infection rate for TNF-exposed patients was 0.168 serious infections per patient year, compared with 0.149 in the control patients (rate ratio 1.12 [95% confidence interval: 0.233-5.404, P = 0.886]. When correcting for time since transplant, the infection rate was 0.194 in the TNF-exposed vs 0.115 in the non-exposed [p = 0.219]. CONCLUSIONS: No significant increase in the rate of serious infection was observed in LT recipients with PSC-IBD during exposure to anti-TNF therapy.

Systematic review: bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?

BACKGROUND: Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis (UC), are chronic conditions attributed to an aberrant immune response to luminal triggers. Recently, published work suggests a pathogenic role for bile acids in this context. AIM: To perform a systematic review of studies investigating the role of bile acids in intestinal inflammation and present potentially relevant clinical implications. METHODS: Pubmed search for English language articles published up to May 2015. Terms used were: 'bile', 'bile acid', 'barrier', 'small bowel injury', 'Crohn's' and 'colitis'. RESULTS: Experimental studies support a variable role for bile acids in intestinal barrier homoeostasis. This may be attributed to different physicochemical properties, variable effects on epithelia and immune cells via bile acids-specific receptors, or through a cross-talk with the gut microbiome. A reduction in the bile acids pool, with lower concentrations of secondary forms, has been recognised for some time in Crohn's disease and associated to ileal dysfunction and bile acids malabsorption. Recent work suggests that these changes, including an increase in sulphated forms, are related to inflammatory activity in both Crohn's disease and UC. The detrimental effects of 'western diet' elements such as emulsifiers and fat, which have been implicated in the development of the current IBD and obesity epidemics, may also be bile acid-mediated. CONCLUSIONS: Although there are only a few observational clinical studies to support an interaction, in vivo human and animal studies support an association between bile acids metabolism, the gut microbiome and intestinal inflammation. This may well prove to have significant diagnostic and therapeutic implications.

Microvascular caliber changes in intramucosal and submucosally invasive esophageal cancer.

BACKGROUND AND STUDY AIM: Intrapapillary capillary loops (IPCLs) show distinct pattern changes corresponding to tumor progression and depth of invasion, important for in vivo characterization of superficial squamous cell carcinoma (SCC). We examined the relation between invasion depth and histopathologic IPCL diameter. PATIENTS AND METHODS: Prospectively, before lesion resection, magnification endoscopy and narrow band imaging were used to identify IPCL patterns of type V1 (corresponding to tumors limited to the mucosa; 10 patients) and type Vn (submucosally invading tumors; 10 patients). Post-resection, IPCL samples (type I [normal mucosa], n = 103; V1, n = 113; Vn, n = 100) were stained with hematoxylin & eosin, CD34, and desmin, and vessel diameter measured using light microscopy. RESULTS: Mean (standard deviation [SD]) histopathologic calibers of IPCLs of types I, V1, and Vn were significantly different, being 7.7 (2.8) µm, 21.9 (7.4) µm, and 65.2 (22.9) µm; type 1 vs. V1, P < 0.001; V1 vs. Vn, P < 0.001. CONCLUSIONS: Magnification endoscopy observation of IPCLs allows in vivo discrimination between intramucosal and submucosally invasive cancer.

Methotrexate for Crohn's disease: experience in a district general hospital.

Controlled trials have demonstrated the efficacy of methotrexate (MTX) in the induction and maintenance of remission in patients with luminal Crohn's disease, but its use outside of specialist centres remains limited. We present a case series of 24 patients treated with parenteral MTX in a district general hospital. Patients received an induction course of 25 mg weekly for 16 weeks, followed by maintenance doses of 15 mg weekly. Nineteen patients achieved remission during the induction period. Of these, 10 were maintained in remission for more than 12 months. In total, there were six relapses within 1 year and five drug withdrawals due to side effects during the observation period. Of the six relapses, three required surgical intervention (with two of these re-starting methotrexate postoperatively) and three were recommenced on maintenance MTX after a short period at an increased dose. Our results are similar to outcomes achieved in large, randomized, controlled trials and indicate that MTX can be used safely and effectively for the treatment of refractory Crohn's disease in the district general hospital setting.