Carolina Palmela

Adherent-invasive Escherichia coli in inflammatory bowel disease

Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli, and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn’s disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.

Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.

Antigenic response to CT-P13 and infliximab originator in inflammatory bowel disease patients shows similar epitope recognition

To test the cross‐immunogenicity of anti‐CT‐P13 IBD patients’ sera to CT‐P13/infliximab originator and the comparative antigenicity evoked by CT‐P13/infliximab originator sera.

Towards curative therapy in gastric cancer: Faraway, so close!

Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer (GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments.

New Trends in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal (GI) tract. In the past decade a shift in the treatment paradigm of IBD has ensued. The availability of drugs capable of inducing mucosal healing, combined with the recognition that IBD is not an intermittent disease, but rather a progressive one causing bowel damage and disability, led us to a more stringent strategy. Tailored therapy with more aggressive treatment in high-risk patients, treating beyond symptoms, intervening early before damage occurs, optimizing therapeutic regimens, and actively pursuing sustained remission and sustained control of inflammation are strategies that are slowly being incorporated in our clinical practice. Furthermore, new drugs targeting different immunological pathways, such as vedolizumab, have recently been approved and therefore more therapeutic resources for patients failing anti-tumour necrosis factor alpha (anti-TNFα) agents will be available. The future years look promising for IBD. Hopefully the new trends in IBD management, combined with new drugs, will make possible to change the course of disease and provide better therapy and quality of life for patients suffering from this disabling disease.Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal (GI) tract. In the past decade a shift in the treatment paradigm of IBD has ensued. The availability of drugs capable of inducing mucosal healing, combined with the recognition that IBD is not an intermittent disease, but rather a progressive one causing bowel damage and disability, led us to a more stringent strategy. Tailored therapy with more aggressive treatment in high-risk patients, treating beyond symptoms, intervening early before damage occurs, optimizing therapeutic regimens, and actively pursuing sustained remission and sustained control of inflammation are strategies that are slowly being incorporated in our clinical practice. Furthermore, new drugs targeting different immunological pathways, such as vedolizumab, have recently been approved and therefore more therapeutic resources for patients failing anti-tumour necrosis factor alpha (anti-TNFα) agents will be available. The future years look promising for IBD. Hopefully the new trends in IBD management, combined with new drugs, will make possible to change the course of disease and provide better therapy and quality of life for patients suffering from this disabling disease.

The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease:

Background Patients with primary sclerosing cholangitis associated with inflammatory bowel disease (PSC-IBD) have a very high risk of developing colorectal neoplasia. Alterations in the gut microbiota and/or gut bile acids could account for the increase in this risk. However, no studies have yet investigated the net result of cholestasis and a potentially altered bile acid pool interacting with a dysbiotic gut flora in the inflamed colon of PSC-IBD. Aim The aim of this study was to compare the gut microbiota and stool bile acid profiles, as well as and their correlation in patients with PSC-IBD and inflammatory bowel disease alone. Methods Thirty patients with extensive colitis (15 with concomitant primary sclerosing cholangitis) were prospectively recruited and fresh stool samples were collected. The microbiota composition in stool was profiled using bacterial 16S rRNA sequencing. Stool bile acids were assessed by high-performance liquid chromatography tandem mass spectrometry. Results The total stool bile acid pool was significantly reduced in PSC-IBD. Although no major differences were observed in the individual bile acid species in stool, their overall combination allowed a good separation between PSC-IBD and inflammatory bowel disease. Compared with inflammatory bowel disease alone, PSC-IBD patients demonstrated a different gut microbiota composition with enrichment in Ruminococcus and Fusobacterium genus compared with inflammatory bowel disease. At the operational taxonomic unit level major shifts were observed within the Firmicutes (73%) and Bacteroidetes phyla (17%). Specific microbiota-bile acid correlations were observed in PSC-IBD, where 12% of the operational taxonomic units strongly correlated with stool bile acids, compared with only 0.4% in non-PSC-IBD. Conclusions Patients with PSC-IBD had distinct microbiota and microbiota-stool bile acid correlations as compared with inflammatory bowel disease. Whether these changes are associated with, or may predispose to, an increased risk of colorectal neoplasia needs to be further clarified.

Adenoma Detection Rate: I Will Show You Mine if You Show Me Yours

Background: Colorectal cancer (CRC) is the first cause of cancer-related mortality in Portugal. CRC screening reduces disease-specific mortality. Colonoscopy is currently the preferred method for screening as it may contribute to the reduction of CRC incidence. This beneficial effect is strongly associated with the adenoma detection rate (ADR). Aim: Our aim was to evaluate the quality of colonoscopy at our unit by measuring the currently accepted quality parameters and publish them as benchmarking indicators. Methods: From 5,860 colonoscopies, 654 screening procedures (with and without previous fecal occult blood testing) were analyzed. Results: The mean age of the patients was 66.4 ± 7.8 years, and the gender distribution was 1:1. The overall ADR was 36% (95% confidence interval [CI] 32-39), the mean number of adenomas per colonoscopy was 0.66 (95% CI 0.56-0.77), and the sessile serrate lesion detection rate was 1% (95% CI 0-2). The bowel preparation was rated as adequate in 496 (76%) patients. The adjusted cecal intubation rate (CIR) was 93.7% (95% CI 91.7-95.8). Most colonoscopies were performed under monitored anesthesia care (53%), and 35% were unsedated. The use of sedation (propofol or midazolam based) was associated with a higher CIR with an odds ratio of 3.60 (95% CI 2.02-6.40, p < 0.001). Conclusion: Our data show an above-standard ADR. The frequency of poor bowel preparation and the low sessile serrated lesion detection rate were acknowledged, and actions were implemented to improve both indicators. Quality auditing in colonoscopy should be compulsory, and while many units may do so internally, this is the first national report from a high-throughput endoscopy unit.

Review ArticleNew Trends in Inflammatory Bowel DiseaseNovas Estratégias Terapêuticas na Doença Inflamatória do Intestino

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal (GI) tract. In the past decade a shift in the treatment paradigm of IBD has ensued. The availability of drugs capable of inducing mucosal healing, combined with the recognition that IBD is not an intermittent disease, but rather a progressive one causing bowel damage and disability, led us to a more stringent strategy. Tailored therapy with more aggressive treatment in high-risk patients, treating beyond symptoms, intervening early before damage occurs, optimizing therapeutic regimens, and actively pursuing sustained remission and sustained control of inflammation are strategies that are slowly being incorporated in our clinical practice. Furthermore, new drugs targeting different immunological pathways, such as vedolizumab, have recently been approved and therefore more therapeutic resources for patients failing anti-tumour necrosis factor alpha (anti-TNFα) agents will be available. The future years look promising for IBD. Hopefully the new trends in IBD management, combined with new drugs, will make possible to change the course of disease and provide better therapy and quality of life for patients suffering from this disabling disease.Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease of the gastrointestinal (GI) tract. In the past decade a shift in the treatment paradigm of IBD has ensued. The availability of drugs capable of inducing mucosal healing, combined with the recognition that IBD is not an intermittent disease, but rather a progressive one causing bowel damage and disability, led us to a more stringent strategy. Tailored therapy with more aggressive treatment in high-risk patients, treating beyond symptoms, intervening early before damage occurs, optimizing therapeutic regimens, and actively pursuing sustained remission and sustained control of inflammation are strategies that are slowly being incorporated in our clinical practice. Furthermore, new drugs targeting different immunological pathways, such as vedolizumab, have recently been approved and therefore more therapeutic resources for patients failing anti-tumour necrosis factor alpha (anti-TNFα) agents will be available. The future years look promising for IBD. Hopefully the new trends in IBD management, combined with new drugs, will make possible to change the course of disease and provide better therapy and quality of life for patients suffering from this disabling disease.

Consecutive negative findings on colonoscopy during surveillance predict a low risk of advanced neoplasia in patients with inflammatory bowel disease with long-standing colitis: results of a 15-year multicentre, multinational cohort study

Objectives Surveillance colonoscopy is thought to prevent colorectal cancer (CRC) in patients with long-standing colonic IBD, but data regarding the frequency of surveillance and the findings thereof are lacking. Our aim was to determine whether consecutive negative surveillance colonoscopies adequately predict low neoplastic risk. Design A multicentre, multinational database of patients with long-standing IBD colitis without high-risk features and undergoing regular CRC surveillance was constructed. A ‘negative’ surveillance colonoscopy was predefined as a technically adequate procedure having no postinflammatory polyps, no strictures, no endoscopic disease activity and no evidence of neoplasia; a ‘positive’ colonoscopy was a technically adequate procedure that included at least one of these criteria. The primary endpoint was advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia or CRC. Results Of 775 patients with long-standing IBD colitis, 44% (n=340) had >1 negative colonoscopy. Patients with consecutive negative surveillance colonoscopies were compared with those who had at least one positive colonoscopy. Both groups had similar demographics, disease-related characteristics, number of surveillance colonoscopies and time intervals between colonoscopies. No aCRN occurred in those with consecutive negative surveillance, compared with an incidence rate of 0.29 to 0.76/100 patient-years (P=0.02) in those having >1 positive colonoscopy on follow-up of 6.1 (P25–P75: 4.6–8.2) years after the index procedure. Conclusion Within this large surveillance cohort of patients with colonic IBD and no additional high-risk features, having two consecutive negative colonoscopies predicted a very low risk of aCRN occurrence on follow-up. Our findings suggest that longer surveillance intervals in this selected population may be safe.

Self-Expandable Metal Stents for Colorectal Cancer: From Guidelines to Clinical Practice

Introduction Colonic self-expandable metal stent placement is widely used for palliation of obstructive colorectal cancer. The European recommendations for stent placement as a bridge to elective surgery in obstructive colorectal cancer were recently reviewed. The aim of this study was to evaluate the efficacy and safety of stent placement in obstructive colorectal cancer and to discuss these recent guidelines. Materials and methods Demographic characteristics, procedure indications, complications and final outcome in patients with obstructive colorectal cancer who underwent endoscopic stent placement between January 2012 and June 2015 were retrospectively analyzed. Statistical analysis was performed with SPSS V22. Results Thirty-six patients were included, 20 (56%) women, mean age 70.6 ± 10.9 years. Stent placement as a bridge to elective surgery was performed in 75% (n = 27) of patients and with palliation intent in 25% (n = 9). In 94% (n = 34) of procedures, technical and clinical success was achieved. A total of eleven (11%) complications were observed: 2 migrations and 9 perforations. No procedure related death was recorded. When stents were placed as a bridge to surgery, average time between endoscopic procedure and surgery was 11.7 ± 9.4 days (excluding three patients who underwent neoadjuvant chemotherapy). Six perforations were recorded in this group: one overt and five silent (three during surgery and two after histopathological examination of the resected specimen). Twenty-one patients underwent adjuvant chemotherapy. During the follow-up period of 14.7 ± 10.9 months recurrence was observed in five patients. None of the recurrence occurred in the group of patients with perforation. Conclusions In this study, stent placement was an effective procedure in obstructive colorectal cancer. It was mainly used as a bridge to elective surgery. However, a significant rate of silent perforation was observed, which may compromise the oncological outcome of these potentially curable patients. Prospective real life studies are warranted for a better definition of actual recommendations.