Narrow Band Imaging versus White Light for the Detection of Sessile Serrated Colorectal Lesions: A Randomized Clinical Trial.

Background: Colorectal cancer (CRC) is a leading cause of cancer. The detection of pre-malignant lesions by colonoscopy is associated with reduced CRC incidence and mortality. Narrow band imaging has shown promising but conflicting results for the detection of serrated lesions. Methods: We performed a randomized clinical trial to compare the mean detection of serrated lesions and hyperplastic polyps ≥10 mm with NBI or high-definition white light (HD-WL) withdrawal. We also compared all sessile serrated lesions (SSLs), adenoma, and polyp prevalence and rates. Results: Overall, 782 patients were randomized (WL group 392 patients; NBI group 390 patients). The average number of serrated lesions and hyperplastic polyps ≥10 mm detected per colonoscopy (primary endpoint) was similar between the HD-WL and NBI group (0.118 vs. 0.156, p = 0.44). Likewise, the adenoma detection rate (55.2% vs. 53.2%, p = 0.58) and SSL detection rate (6.8% vs. 7.5%, p = 0.502) were not different between the two study groups. Withdrawal time was higher in the NBI group (10.88 vs. 9.47 min, p = 0.004), with a statistically nonsignificant higher total procedure time (20.97 vs. 19.30 min, p = 0.052). Conclusions: The routine utilization of narrow band imaging does not improve the detection of serrated class lesions or any pre-malignant lesion and increases the withdrawal time.

Introdução: O cancro do cólon e reto é a neoplasia mais frequente considerando os dois géneros. . A deteção de lesões pré-malignas por colonoscopia está associada a uma redução da incidência e da mortalidade. Estudos sobre a utilização da luz de banda estreita (NBI) na deteção de lesões serreadas tiveram resultados promissores, mas heterogéneos. Métodos: Realizámos um ensaio clínico randomizado para comparar o número médio de lesões serreadas e lesões hiperplásicas ≥10 mm com NBI ou luz branca de alta-definição (HD-WL). Como resultados secundários comparámos a prevalência e as taxas de deteção de lesões serreadas sésseis, adenomas e todas as lesões. Resultados: Foram randomizados 782 doentes (392 no grupo HD-WL e 390 no grupo NBI). O número médio de lesões serreadas e hiperplásicas ≥10 mm não apresentou diferença estatisticamente significativa entre dois grupos (0.118 vs. 0.156, p = 0.44). A taxa de deteção de adenomas (55.2% vs. 53.2%, p = 0.58) e a taxa de deteção de lesões serreadas sésseis (6.8% vs. 7.5%, p = 0.502) também não foram diferentes. O tempo de retirada foi maior no grupo NBI (10.88 vs. 9.47 min, p = 0.004) e o tempo total de procedimento teve um ligeiro aumento não atingindo significância estatística (20.97 vs. 19.30 min, p = 0.052). Conclusão: A utilização da luz NBI por rotina não aumenta a deteção de lesões serreadas nem de qualquer lesão pré-maligna e aumenta o tempo de retirada na colonoscopia.

Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Intestinal Ultrasound in Inflammatory Bowel Disease: A Valuable and Increasingly Important Tool.

Background: Intestinal ultrasound is emerging as a non-invasive tool for monitoring disease activity in inflammatory bowel disease patients due to its low cost, excellent safety profile, and availability. Herein, we comprehensively review the role of intestinal ultrasound in the management of these patients. Summary: Intestinal ultrasound has a good accuracy in the diagnosis of Crohn's disease, as well as in the assessment of disease activity, extent, and evaluating disease-related complications, namely strictures, fistulae, and abscesses. Even though not fully validated, several scores have been developed to assess disease activity using ultrasound. Importantly, intestinal ultrasound can also be used to assess response to treatment. Changes in ultrasonographic parameters are observed as early as 4 weeks after treatment initiation and persist during short- and long-term follow-up. Additionally, Crohn's disease patients with no ultrasound improvement seem to be at a higher risk of therapy intensification, need for steroids, hospitalisation, or even surgery. Similarly to Crohn's disease, intestinal ultrasound has a good performance in the diagnosis, activity, and disease extent assessment in ulcerative colitis patients. In fact, in patients with severe acute colitis, higher bowel wall thickness at admission is associated with the need for salvage therapy and the absence of a significant decrease in this parameter may predict the need for colectomy. Short-term data also evidence the role of intestinal ultrasound in evaluating therapy response, with ultrasound changes observed after 2 weeks of treatment and significant improvement after 12 weeks of follow-up in ulcerative colitis. Key Messages: Intestinal ultrasound is a valuable tool to assess disease activity and complications, and to monitor response to therapy. Even though longer prospective data are warranted, intestinal ultrasound may lead to a change in the paradigm of inflammatory bowel disease management as it can be used in a point-of-care setting, enabling earlier intervention if needed.

Contexto: A ecografia intestinal na doença inflamatória intestinal tem ganho importância crescente como exame não invasivo para monitorizar a atividade de doença, pelos seus custos reduzidos, excelente perfil de segurança e disponibilidade. Neste artigo realizamos uma revisão sobre o papel da ecografia intestinal no manejo destes doentes. Sumário: Na doença de Crohn, a ecografia intestinal tem uma boa acuidade no diagnóstico, avaliação da atividade e extensão da doença, assim como na avaliação de complicações, como estenoses, fístulas e abcessos. Apesar de não estarem validados, vários scores têm sido desenvolvidos para avaliar a atividade de doença. É de realçar a importância da ecografia intestinal na avaliação da resposta à terapêutica.A melhoria dos parâmetros ecográficos é observada tão precocemente como quatro semanas e persiste durante o seguimento a curto e longo prazo. Os doentes sem melhoria ecográfica parecem ter uma maior necessidade de intensificação terapêutica, corticóides, internamento ou cirurgia. À semelhança da doença de Crohn, a ecografia intestinal tem uma boa acuidade na avaliação ao diagnóstico, atividade e extensão da doença na colite ulcerosa. Na colite ulcerosa grave, um maior espessamento da parede intestinal à admissão está associado a maior necessidade de terapêutica de resgate e a ausência de melhoria deste parâmetro pode predizer a necessidade de colectomia. A ecografia também permite a avaliação da resposta à terapêutica na colite ulcerosa, com alterações observadas após duas semanas de tratamento e mantendo melhoria significativa após 12 semanas. Mensagemchave: A ecografia intestinal é um método importante para avaliar a atividade de doença, complicações e monitorizar a resposta à terapêutica na doença inflamatória intestinal. Apesar de serem necessários mais estudos prospetivos, a ecografia intestinal pode levar a uma mudança de paradigma no manejo destes doentes, uma vez que pode ser utilizada no momento de prestação de cuidados, permitindo uma intervenção precoce quando necessário.

Phenotype-Genotype Correlation in Colorectal Cancer: A Real-Life Study.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a heterogeneous disease with distinctive genetic pathways, such as chromosomal instability, microsatellite instability and methylator pathway. Our aim was to correlate clinical and genetic characteristics of CRC patients in order to understand clinical implications of tumour genotype. METHODS: Single-institution retrospective cohort of patients who underwent curative surgery for CRC, from 2012 to 2014. RAS and BRAF mutations were evaluated with the real-time PCR technique Idylla®. Mismatch repair deficiency (dMMR) was characterized by absence of MLH1, MSH6, MSH2 and/or PMS2 expression, evaluated by tissue microarrays. Overall survival (OS) and disease-free survival (DFS) were assessed using survival analysis. RESULTS: Overall, 242 patients were included (males 57.4%, age 69.3 ± 12.9 years; median follow-up 49 months). RAS-mutated tumours were associated with reduced DFS (p = 0.02) and OS (p = 0.045) in stage I-III CRC. BRAF-mutated tumours were more predominant in females and in the right colon, similarly to dMMR tumours. BRAF status did not influence OS (4 years)/DFS (3.5 years) in stage I-III disease. However, after relapse, length of survival was 3.5 months in BRAF-mutated tumours in contrast to 18.6 months in BRAF wild-type tumours (p = NS). No germline mutations in mismatch repair genes were so far identified in the patients with dMMR tumours. Molecular phenotype (RAS, BRAF and MMR) did not influence OS in metastatic patients. Our small sample size may be a limitation of the study. CONCLUSION: In our cohort, RAS-mutated tumours were associated with worse DFS and OS in early-stage CRC, whereas the remaining molecular variables had no prognostic influence.

INTRODUÇÃO: O cancro colo-rectal (CCR) é uma doença heterogénea, com vias genéticas distintas, nomeadamente instabilidade cromossómica, instabilidade de microssatélites e via metiladora. O nosso objetivo foi correlacionar as características clínicas e genéticas dos doentes com CCR e, deste modo, conhecer as implicações na prática clínica do genótipo tumoral. MÉTODOS: Estudo de coorte retrospectivo unicêntrico de doentes diagnosticados com CCR e submetidos a cirurgia com intuito curativo, entre 2012 e 2014. As mutações RAS e BRAF foram avaliadas pela técnica de real time PCR Idylla®. A deficiência de mismatch repair (MMR) foi avaliada pela técnica de tissue microarrays e definida pela ausência de expressão de MLH1, MSH6, MSH2 e/ou PMS2. A sobrevivência global (SG) e a sobrevivência livre de doença (SLD) foram avaliadas por análise de sobrevivência. RESULTADOS: No total, foram incluídos 242 doentes (homens 57.4%, idade 69.3 ± 12.9 anos, mediana de seguimento de 49 meses). Os tumores RAS-mutados associaram-se a menor SLD (p = 0.02) e SG (p = 0.045) em doentes com CCR estadio I­III. Os tumores BRAF-mutados foram mais frequentes em mulheres e nos tumores do cólon direito, assim como os tumores com deficiência para MMR. O status BRAF não influenciou a SG (4 anos)/SLD (3.5 anos) nos estadio I­III. Contudo, após a recidiva, o tempo de sobrevivência foi de 3.5 meses nos tumores BRAF-mutados, em comparação com 18.6 meses nos tumores sem esta mutação (p = NS). Não se identificaram mutações germinativas nos genes de mismatch repair nos doentes com tumores deficientes para estas proteinas (dMMR). O perfil molecular (RAS, BRAF e MMR) não influenciou a sobrevivência global dos doentes com metástases ao diagnóstico. O tamanho da amostra pode ser uma limitação do estudo. CONCLUSÃO: Na nossa coorte, os tumores RASmutados associaram-se a pior SLD e SG nos estádios precoces de CCR. Os restantes marcadores moleculares não influenciaram o prognóstico dos doentes.

Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis.

BACKGROUND: The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed. METHODS: This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation). RESULTS: Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04). CONCLUSIONS: The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.

Inflammatory Bowel Disease Patients' Perspectives during COVID-19 Pandemic: Results from a Portuguese Survey.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) do not seem to be at increased risk of infection by SARS-CoV-2, but there is a concern whether immunosuppressive therapy may be associated with more severe disease. Several clinical practice recommendations have been published to help guide IBD care during the COVID-19 pandemic. Nonetheless, few studies have addressed patients' perspectives and fears. We aimed to evaluate Portuguese IBD patients' perspectives on the clinical management of their disease during the SARS-CoV-2 pandemic as well as the impact on their professional life. METHODS: An anonymous electronic survey was created using REDCap and was distributed by the Portuguese Association of Inflammatory Bowel Disease (APDI) between May and August 2020. Patients' perspectives on immunosuppressive therapy, disease management, interaction with gastroenterology departments, and the impact of the pandemic in their professional life were assessed. Patients' proposals to improve medical care were also evaluated. Descriptive analysis and logistic regression were performed. RESULTS: A total of 137 participants answered the survey (79.6% females, mean age 41.7 ± 12.1 years). Although having IBD and receiving treatment with immunosuppressors (thiopurines, steroids, or biologics) were considered promotors of anxiety, most patients (85.4%) agreed that disease remission was a priority and only a minority of patients interrupted their treatment during the pandemic. In multivariate analysis, active disease, biologic treatment, and use of corticosteroids in the last 3 months were perceived by the patients as high-risk features for increased risk of SARS-Cov-2 infection and more severe disease. Fifty-nine patients (44%) believed that their follow-up was influenced by the pandemic and only 58.8% felt that they had the opportunity to discuss their therapeutic options with their doctor. Sixty-three patients (46.0%) were working from home during the pandemic, although this decision was related to IBD and immunosuppressive therapy in only 36.5 and 39.7% of the cases, respectively. Areas where care could have been improved during the pandemic were identified by patients, namely enhancement of the communication with IBD professionals, conciliation of telemedicine with face-to-face appointments, and facilitation of the interaction between patients and employers. CONCLUSION: Most patients agreed that maintaining IBD remission is crucial, and only a minority of the patients stopped their treatment as per their own initiative. IBD status only had a small influence on patients' professional activity during the COVID-19 outbreak, with most changes being related to the pandemic itself.

Early life exposures and the risk of inflammatory bowel disease: Systematic review and meta-analyses.

BACKGROUND: Early life exposures impact immune system development and therefore the risk of immune-mediated diseases, including inflammatory bowel disease (IBD). We systematically reviewed the impact of pre-, peri­, and postnatal exposures up to the age of five years on subsequent IBD diagnosis. METHODS: We identified case-control and cohort studies reporting on the association between early life environmental factors and Crohn's disease (CD), ulcerative colitis (UC), or IBD overall. Databases were search from their inception until May 24th, 2019 until July 14th, 2020. We conducted meta-analyses for quantitative review of relevant risk factors that were comparable across studies and qualitative synthesis of the literature for a wide range of early life exposures, including maternal health and exposures during pregnancy, perinatal factors, birth month and related-factors, breastfeeding, hygiene-related factors and social factors, immigration, antibiotics, offspring health, including infections, and passive smoking. PROSPERO registration: CRD42019134980. FINDINGS: Prenatal exposure to antibiotics (OR 1.8; 95% CI 1.2-2.5) and tobacco smoke (OR 1.5; 95% CI 1.2-1.9), and early life otitis media (OR 2.1; 95% CI 1.2-3.6) were associated with IBD. There was a trend towards an association between exposure to antibiotics in infancy and IBD (OR: 1.7, 95% CI 0.97, 2.9), supported by positive data on population-based data. Breastfeeding was protective against IBD. Other early life risk factors had no association with IBD, but data were limited and heterogenous. INTERPRETATION: Early life is an important period of susceptibility for IBD development later in life. Tobacco smoke, infections and antibiotics were associated positively, and breastfeeding was associated negatively with IBD. Our findings offer an opportunity to develop primary prevention strategies. FUNDING: This study did not receive any funding.

Conjugal inflammatory bowel disease: a systematic review and European survey.

BACKGROUND: The frequency of inflammatory bowel disease (IBD) is increased after marriage to an individual with the disease. Importantly, the offspring of these couples have a significant risk for developing the disease. Herein, we aimed to better characterize conjugal IBD. METHODS: A systematic literature search was conducted with predetermined search criteria. Relevant manuscripts reporting on couples with IBD and their offspring were selected. Concomitantly, a cross-sectional survey was conducted of couples where both members were affected with IBD, as well as their offspring, and electronically distributed by patients' associations. RESULTS: We identified 20 reports of IBD in couples, for a total of 68 couples. Of these, 66% were concordant regarding IBD type and 66% were diagnosed after cohabitation. The overall prevalence of IBD in the offspring of these couples was 29%. Our survey identified 58 couples with IBD, with 62% being concordant regarding IBD type; 42.9% were diagnosed prior to cohabitation, in 12.5% one spouse was diagnosed before and the other after cohabitation, and in 44.6% the onset of disease occurred after cohabitation for both. The prevalence of IBD in children born from these couples was 10%. The probability of developing disease in the progeny was 2% at 10 years, 12% at 15 years, and 16% at 20 years of age. CONCLUSIONS: IBD in couples occurs mostly after marriage to an individual with disease or after many years of cohabitation. In a modern cohort, the risk for the progeny was around 16% by the age of 20, lower than previously reported.

Mode of Delivery Does Not Affect the Risk of Inflammatory Bowel Disease.

BACKGROUND: Recent evidence suggests that exposures in early life that are known to influence microbiome development may affect the risk of developing inflammatory bowel disease (IBD). Cesarean section has been associated with altered colonization of commensal gut flora and is thought to predispose to immune-mediated diseases later in life. AIMS: To evaluate the risk of IBD, Crohn's Disease (CD), and Ulcerative Colitis (UC) according to mode of delivery (C-section vs vaginal delivery). METHODS: A systematic search was performed in PubMed and Embase. The primary outcome was the risk of IBD in individuals delivered vaginally compared to those born by C-section. Secondary outcomes were UC and CD risk according to mode of delivery and IBD risk in individuals born by emergent compared to elective C-section. Publication bias was evaluated by funnel plots and Egger's test. Study's quality was characterized using the Newcastle-Ottawa Scale. RESULTS: Ten studies fulfilled the inclusion criteria, of which seven were population-based. No publication bias was detected. Overall, 14.164 IBD patients and 4.206.763 controls were included. Being born by C-section was not associated with increased risk of IBD [OR 1.01, 95% CI (0.81-1.27), p = 0.92], CD [OR 1.15, 95% CI (0.94-1.42), p = 0.18] or UC [OR 0.94, 95% CI (0.61-1.45), p = 0.79]. No differences were found between emergent and elective C-section in IBD [OR 1.05, 95% CI (0.59-1,87), p = 0.87]. Substantial heterogeneity was found in statistical analysis, and further studies are needed. CONCLUSION: Overall, the risk of developing IBD was not affected by mode of delivery.

De-escalation of medical therapy in inflammatory bowel disease.

Treatment strategies for inflammatory bowel disease (IBD) now increasingly target deep remission, yet the resultant more aggressive use of medical therapy is associated with potentially serious adverse events and significant costs. It is, therefore, of vital importance to consider when, how and in whom medical therapy may be safely de-escalated. This issue is of great potential relevance in the current SARS-Cov-2 pandemic. In this review, we first discuss the rationale for drug withdrawal in IBD, before considering the available data on withdrawal of 5-aminosalicylates (5-ASA), immunomodulators (IM) and biological therapy in both ulcerative colitis (UC) and Crohn's Disease (CD). We consider how to identify patients most appropriate for drug withdrawal and outline a potential monitoring strategy for the early detection of relapse following drug withdrawal. We conclude with important future perspectives in this challenging field, and highlight ongoing trials that are likely to shape practice in the years to come.

Review article: withdrawal of 5-aminosalicylates in inflammatory bowel disease.

BACKGROUND: 5-aminosalicylates (5-ASA) are widely used in inflammatory bowel disease (IBD), but emerging evidence suggests that they may be safely withdrawn in significant subsets of patients. This is important to address: 5-ASA therapy accounts for up to 25% of total healthcare costs in ulcerative colitis (UC), while almost a third of patients with Crohn's disease (CD) receive long-term 5-ASA despite no clear evidence of benefit. Further, rationalising medication burden may improve overall adherence and outcome. AIMS: To summarise the rationale for 5-ASA withdrawal, review the current evidence in both UC and CD and consider the data surrounding colorectal cancer (CRC) prevention, guiding an evidence-based withdrawal strategy. METHODS: PubMed was searched to identify relevant studies. Only papers published in English were reviewed, with priority given to randomised clinical trials and meta-analyses. RESULTS: For patients with UC, consideration of 5-ASA withdrawal should be made on a case-by-case basis, but it appears safest for those in deep remission without any of the following risk factors: younger age (<40 years), remission for less than 2 years, a history of multiple flares, extensive disease. 5-ASA withdrawal should also be considered in patients with UC escalated to biologic therapy who have achieved remission and in all patients with CD. Although 5-ASA therapy may have chemopreventive benefits for CRC, the cost-benefit ratio appears significant, and this indication is not justified by evidence in those who have achieved remission and are continuing therapy with other agents, or in those in sustained remission without a history of extensive disease. CONCLUSIONS: Although the majority of patients with IBD receive 5-ASA during their disease course, safe withdrawal appears possible in many, with important implications for both health economics and patient experience. A number of unanswered questions, however, remain.

De-escalation of Therapy in Inflammatory Bowel Disease.

PURPOSE OF REVIEW: Currently, inflammatory bowel disease treatment is based on immunomodulators (IM) and/or biologic as this strategy may prevent the development of irreversible damage. Nevertheless, long-term treatment may be associated with non-negligible side effects and with high costs, and therefore the question on whether therapy can be de-escalated is often posed in clinical practice. RECENT FINDINGS: Recent studies have shown a predictable rate of relapse after stop biologic or IM therapy withdrawal. Overall, around 40-50% of patients will eventually relapse over the following year after drug withdrawal, and the rates will increase over time. Stratification of patients and therapeutic drug monitoring could be promising alternatives to guide therapeutic management. We reviewed the current evidence on de-escalation strategy and summarised the recent results on discontinuation and dose reduction. Nowadays, de-escalation strategy is still a case-by-case decision in highly selected patients.