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PURPOSE: Comparative studies on efficacy of treatment strategies for anastomotic leakage (AL) after low anterior resection (LAR) are almost non-existent. This study aimed to compare different proactive and conservative treatment approaches for AL after LAR. METHODS: This retrospective cohort study included all patients with AL after LAR in three university hospitals. Different treatment approaches were compared, including a pairwise comparison of conventional treatment and endoscopic vacuum-assisted surgical closure (EVASC). Primary outcomes were healed and functional anastomosis rates at end of follow-up. RESULTS: Overall, 103 patients were included, of which 59 underwent conventional treatment and 23 EVASC. Median number of reinterventions was 1 after conventional treatment, compared to 7 after EVASC (p < 0.01). Median follow-up was 39 and 25 months, respectively. Healed anastomosis rate was 61% after conventional treatment, compared to 78% after EVASC (p = 0.139). Functional anastomosis rate was higher after EVASC, compared to conventional treatment (78% vs. 54%, p = 0.045). Early initiation of EVASC in the first week after primary surgery resulted in better functional anastomosis rate compared to later initiation (100% vs. 55%, p = 0.008). CONCLUSION: Proactive treatment of AL consisting of EVASC resulted in improved healed and functional anastomosis rates for AL after LAR for rectal cancer, compared to conventional treatment. If EVASC was initiated within the first week after index surgery, a 100% functional anastomosis rate was achievable.
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INTRODUCTION: Intestinal ultrasound [IUS] is useful for assessment of inflammation, complications, and treatment follow-up in inflammatory bowel disease [IBD] patients. We aimed to study outcomes and impact on disease management for point-of-care [POC] IUS in IBD patients. METHODS: Two patient cohorts undergoing POC IUS [January 2016-July 2018 and October 2019-December 2019] were included retrospectively. Disease management after IUS was analysed and IUS outcomes were compared with symptoms, biomarkers, and additional imaging within 8 weeks from IUS. To study differences in use of IUS over time, cohorts were compared. RESULTS: In total, 345 examinations (280 in Crohn's disease [CD]/65 in ulcerative colitis [UC]) were performed. Present inflammation on IUS was comparable between symptomatic and asymptomatic CD [67.6% vs 60.5%; pâ =â 0.291]. In 60%, IUS had impact on disease management with change in medication in 47.8%. Additional endoscopy/magnetic resonance imaging [MRI] was planned after 32.8% examinations, showing good correlation with IUS in 86.3% [ρâ =â 0.70, pâ <0.0001] and 80.0% [ρâ =â 0.75, pâ <0.0001] of cases, respectively. Faecal calprotectin was higher in active versus inactive disease on IUS [664 µg/g vs 79 µg/g; pâ <0.001]. Over the years, IUS was performed more frequently to monitor treatment response and the use of MRI was reduced within the cohort. CONCLUSIONS: POC IUS affects clinical decision making and could detect preclinical relapse in CD patients, with potential to reduce additional endoscopy or MRI. In addition, the paradigm expands towards monitoring treatment and close follow-up for IUS. Based on our results, we propose a POC IUS algorithm for follow-up of IBD patients.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Algoritmos , Doença Crônica , Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/complicações , Doença de Crohn/diagnóstico por imagem , Gerenciamento Clínico , Fezes , Humanos , Inflamação/complicações , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Sistemas Automatizados de Assistência Junto ao Leito , Estudos RetrospectivosRESUMO
AIM: Although has been suggested that an appendectomy has a positive effect on the disease course in patients with ulcerative colitis (UC), recent studies indicate a potential increase in risk of colectomy and colorectal cancer (CRC). This study aimed to evaluate the rates of colectomy and CRC after appendectomy in UC patients using a nationwide prospective database [the Initiative on Crohn and Colitis Parelsnoer Institute - Inflammatory Bowel Disease (ICC PSI-IBD) database]. METHOD: All UC patients were retrieved from the ICC PSI-IBD database between January 2007 and May 2018. Primary outcomes were colectomy and CRC. Outcomes were compared in patients with and without appendectomy, with a separate analysis for timing of appendectomy (before or after UC diagnosis). RESULTS: A total of 826 UC patients (54.7% female; median age 46 years, range 18-89 years) were included. Sixty-three (7.6%) patients had previously undergone appendectomy: 24 (38.1%) before and 33 (52.4%) after their diagnosis of UC. In multivariate analysis, appendectomy after UC diagnosis was associated with a significantly lower colectomy rate compared with no appendectomy [hazard ratio (HR) 0.16, 95% C: 0.04-0.66, P = 0.011], and the same nonsignificant trend was seen in patients with an appendectomy before UC diagnosis (HR 0.35, 95% CI 0.08-1.41, P = 0.138). Appendectomy was associated with delayed colectomy, particularly when it was performed after diagnosis of UC (P = 0.009). No significant differences were found in the CRC rate between patients with and without appendectomy (1.6% vs 1.2%; P = 0.555). CONCLUSION: Appendectomy in established UC is associated with an 84% decreased risk of colectomy and a delay in surgery. Since the colon is in situ for longer, the risk of developing CRC remains, which underscores the importance of endoscopic surveillance programmes.
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Colite Ulcerativa , Neoplasias Colorretais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia , Colectomia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Anastomotic leakage (AL) is still a common and feared complication after low anterior resection (LAR) for rectal cancer. The multifactorial pathophysiology of AL and lack of standardised treatment options requires a multi-modal approach to improve long-term anastomotic integrity. The objective of the IMARI-trial is to determine whether the one-year anastomotic integrity rate in patients undergoing LAR for rectal cancer can be improved using a multi-interventional program. METHODS: IMARI is a multicentre prospective clinical effectiveness trial, whereby current local practice (control cohort) will be evaluated, and subsequently compared to results after implementation of the multi-interventional program (intervention cohort). Patients undergoing LAR for rectal cancer will be included. The multi-interventional program includes three preventive interventions (mechanical bowel preparation with oral antibiotics, tailored full splenic flexure mobilization and intraoperative fluorescence angiography using indocyanine green) combined with a standardised pathway for early detection and active management of AL. The primary outcome is anastomotic integrity, confirmed by CT-scan at one year postoperatively. Secondary outcomes include incidence of AL, protocol compliance and association with AL, temporary and permanent stoma rate, reintervention rate, quality of life and functional outcome. Microbiome analysis will be conducted to investigate the role of the rectal microbiome in AL. In a Dutch nationwide study, the AL rate was 20%, with anastomotic integrity of 90% after one year. Based on an expected reduction of AL due to the preventive approaches of 50%, and increase of anastomotic integrity by a standardised pathway for early detection and active management of AL, we hypothesised that the anastomotic integrity rate will increase from 90 to 97% at one year. An improvement of 7% in anastomotic integrity at one year was considered clinically relevant. A total number of 488 patients (244 per cohort) are needed to detect this difference, with 80% statistical power. DISCUSSION: The IMARI-trial is designed to evaluate whether a multi-interventional program can improve long-term anastomotic integrity after rectal cancer surgery. The uniqueness of IMARI lies in the multi-modal design that addresses the multifactorial pathophysiology for prevention, and a standardised pathway for early detection and active treatment of AL. TRIAL REGISTRATION: Trialregister.nl ( NL8261 ), January 2020.
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Protectomia , Neoplasias Retais , Anastomose Cirúrgica , Fístula Anastomótica , Humanos , Estudos Prospectivos , Qualidade de VidaRESUMO
AIM: To investigate whether subjective radiologist grading of motility on magnetic resonance enterography (MRE) is as effective as software quantification, and to determine the combination of motility metrics with the strongest association with symptom severity. MATERIALS AND METHODS: One hundred and five Crohn's disease patients (52 male, 53 female, 16-68 years old, mean age 34 years old) recruited from two sites underwent MRE, including a 20 second breath-hold cine motility sequence. Each subject completed a Harvey-Bradshaw Index (HBI) symptom questionnaire. Five features within normally appearing bowel were scored visually by two experienced radiologists, and then quantified using automated analysis software, including (1) mean motility, (2) spatial motility variation, (3) temporal motility variation, (4) area of motile bowel, (5) intestinal distension. Multivariable linear regression derived the combination of features with the highest association with HBI score. RESULTS: The best automated metric combination was temporal variation (p<0.05) plus area of motile bowel (p<0.05), achieving an R2 adjusted value of 0.036. Spatial variation was also associated with symptoms (p<0.05, R2 adjusted = 0.034); however, when visually assessed by radiologists, none of the features had a significant relationship with the HBI score. CONCLUSION: Software quantified temporal and spatial variability in bowel motility are associated with abdominal symptoms in Crohn's disease. Subjective radiologist assessment of bowel motility is insufficient to detect aberrant motility. Automated analysis of motility patterns holds promise as an objective biomarker for aberrant physiology underlying symptoms in enteric disorders.
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Doença de Crohn/diagnóstico por imagem , Motilidade Gastrointestinal/fisiologia , Intestino Delgado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adolescente , Adulto , Idoso , Doença de Crohn/fisiopatologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Intestino Delgado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Radiologistas , Índice de Gravidade de Doença , Software , Adulto JovemRESUMO
INTRODUCTION: Real-life patterns of anti-tumour necrosis factor (anti-TNF) use remain largely unknown. We aimed to investigate survival rates, clinical outcomes and costs of anti-TNF agents in a large population of patients with inflammatory bowel disease (IBD). METHODS: Health insurance data from 22,082 IBD patients were provided by Achmea Healthcare. Time to anti-TNF discontinuation, treatment intensification, corticosteroid initiation and hospitalisation were analysed in patients starting on anti-TNF treatment from January 2008 until December 2014. Treatment regimens were analysed at different time points. RESULTS: In this cohort, 855 and 1199 subjects started infliximab and adalimumab treatment, respectively. The median time to anti-TNF discontinuation was 600 days (IQR 156-1693). The proportion of subjects receiving intensified treatment increased over time (infliximab at 3 vs. 24 months: 22.2% vs. 33.6%, p = 0.01; adalimumab at 3 vs. 24 months: 10.5% vs. 19.3%, p < 0.001). Cessation of anti-TNF treatment was less common in Crohn's disease patients (HR 0.79, p = 0.001) and in patients receiving intensified treatment (HR 0.62, p = 0.001). Immunomodulator use was associated with a longer time to corticosteroid initiation (HR 0.80, p = 0.048), but not with longer drug survival (HR 0.99, p = 0.617). Hospitalisation was more common in Crohn's patients (HR 1.49, p = 0.011). Corticosteroid initiation was lower in Crohn's patients (HR 0.57, p < 0.001) and in patients using infliximab (HR 0.55, p < 0.001). CONCLUSIONS: Discontinuation of anti-TNF therapy occurred earlier than previously reported and was associated with a diagnosis of ulcerative colitis and non-intensified anti-TNF treatment. Immunomodulator use at the start of anti-TNF treatment was associated with a longer time to corticosteroid initiation, but not with longer drug survival.
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Adalimumab/uso terapêutico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/economia , Corticosteroides/uso terapêutico , Adulto , Estudos de Coortes , Custos de Medicamentos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Fatores Imunológicos/economia , Infliximab/economia , Seguro Saúde , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Países Baixos , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: The number of patients with inflammatory bowel disease [IBD], of non-Caucasian descent in Western Europe, is increasing. We aimed to explore the impact of ethnicity and country of birth on IBD phenotype. METHODS: IBD patients treated in the eight University Medical Centers in The Netherlands [Dutch IBD Biobank] were divided into two groups according to their ethnicity: 1] Caucasian patients of Western and Central European descent [CEU]; and 2] patients of non-Caucasian descent [non-CEU]. The non-CEU group was subdivided according to country of birth, into: born in The Netherlands or Western Europe [non-CEU European born]; or born outside Western-Europe who migrated to The Netherlands [non-CEU non-European born]. Both comparisons were analysed for phenotype differences [by chi-square test]. RESULTS: The Dutch IBD Biobank included 2921 CEU patients and 233 non-CEU patients. Non-CEU Crohn's disease [CD] patients more often had upper gastro-intestinal disease [16% vs 8%, p = 0.001] and anal stenosis [10% vs 4%, p = 0.002] than CEU CD patients. The use of anti-tumour necrosis factor [TNF] agents and immunomodulators was higher in non-CEU IBD patients than in CEU IBD patients [45% vs 38%, p = 0.042] and [77% vs 66%, p = 0.001], respectively. Non-CEU IBD patients born in Europe [n = 116] were diagnosed at a lower age than non-CEU IBD patients born outside Europe [n = 115] [at 22.7 vs 28.9 years old, p < 0.001]. CONCLUSION: Non-Caucasians had more severe disease behaviour than Caucasians. Non-CEU patients born in Europe were diagnosed at a lower age with IBD than those born outside Europe who migrated to The Netherlands.
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Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Fístula Intestinal/etnologia , Fenótipo , Características de Residência , Adulto , Idade de Início , Idoso , Canal Anal/patologia , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Constrição Patológica/etnologia , Doença de Crohn/genética , Doença de Crohn/terapia , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Despite improvements in medical therapy, the majority of patients with Crohn's disease still require surgery. The aim of this study was to report safety, and clinical and surgical recurrence rates, including predictors of recurrence, after ileocaecal resection for Crohn's disease. METHODS: This was a cohort analysis of consecutive patients undergoing a first ileocaecal resection for Crohn's disease between 1998 and 2013 at one of two specialist centres. Anastomotic leak rate and associated risk factors were assessed. Kaplan-Meier estimates were used to describe long-term clinical and surgical recurrence. Univariable and multivariable regression analyses were performed to identify risk factors for both endpoints. RESULTS: In total, 538 patients underwent primary ileocaecal resection (40·0 per cent male; median age at surgery 31 (i.q.r. 24-42) years). Median follow-up was 6 (2-9) years. Fifteen of 507 patients (3·0 per cent) developed an anastomotic leak. An ASA fitness grade of III (odds ratio (OR) 4·34, 95 per cent c.i. 1·12 to 16·77; P = 0·033), preoperative antitumour necrosis factor therapy (OR 3·30, 1·09 to 9·99; P = 0·035) and length of resected bowel specimen (OR 1·06, 1·03 to 1·09; P < 0·001) were significant risk factors for anastomotic leak. Rates of clinical recurrence were 17·6, 45·4 and 55·0 per cent after 1, 5 and 10 years respectively. Corresponding rates of requirement for further surgery were 0·6, 6·5 and 19·1 per cent. Smoking (hazard ratio (HR) 1·67, 95 per cent c.i. 1·14 to 2·43; P = 0·008) and a positive microscopic resection margin (HR 2·16, 1·46 to 3·21; P < 0·001) were independent risk factors for clinical recurrence. Microscopic resection margin positivity was also a risk factor for further surgery (HR 2·99, 1·36 to 6·54; P = 0·006). CONCLUSION: Ileocaecal resection achieved durable medium-term remission, but smoking and resection margin positivity were risk factors for recurrence.
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Ceco/cirurgia , Doença de Crohn/cirurgia , Íleo/cirurgia , Adulto , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica , Feminino , Humanos , Laparoscopia , Masculino , Complicações Pós-Operatórias , Recidiva , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIM: T cells are key players in the chronic intestinal inflammation that characterises Crohn's disease. Here we aim to map the intestinal T-cell receptor [TCR] repertoire in patients with Crohn's disease, using next-generation sequencing technology to examine the clonality of the T-cell compartment in relation to mucosal inflammation and response to therapy. METHODS: Biopsies were taken from endoscopically inflamed and uninflamed ileum and colon of 19 patients with Crohn's disease. From this cohort, additional biopsies were taken after 8 weeks of remission induction therapy from eight responders and eight non-responders. Control biopsies from 11 patients without inflammatory bowel disease [IBD] were included. The TCRß repertoire was analysed by next-generation sequencing of biopsy RNA. RESULTS: Both in Crohn's disease patients and in non-IBD controls, a broad intestinal T-cell repertoire was found, with a considerable part consisting of expanded clones. Clones in Crohn's disease were more expanded [p = 0.008], with the largest clones representing up to as much as 58% of the total repertoire. There was a substantial overlap of the repertoire between inflamed and uninflamed tissue and between ileum and colon. Following therapy, responders showed larger changes in the T-cell repertoire than non-responders, although a considerable part of the repertoire remained unchanged in both groups. CONCLUSIONS: The intestinal T-cell repertoire distribution in Crohn's disease is different from that in the normal gut, containing profoundly expanded T-cell clones that take up a large part of the repertoire. The T-cell repertoire is fairly stable regardless of endoscopic mucosal inflammation or response to therapy.
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Doença de Crohn/imunologia , Doença de Crohn/patologia , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Linfócitos T/patologia , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Biópsia , Budesonida/uso terapêutico , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Células Clonais/efeitos dos fármacos , Colo/patologia , Doença de Crohn/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Íleo/patologia , Inflamação/imunologia , Inflamação/patologia , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Linfócitos T/efeitos dos fármacos , Adulto JovemRESUMO
AIM: During the last decade, treatment protocols have changed for patients with ileocolic Crohn's disease. Anti-tumour necrosis factor (anti-TNF) has become part of standard medical treatment, usually in a step-up approach. The aim was to analyse if improved medical treatment has resulted in more limited ileocolic resections and a longer interval between diagnosis and surgery. METHOD: Patients undergoing ileocolic resection for Crohn's disease were included (1999-2014). Patient characteristics were compared to the results of a population-based study (between 2004 and 2010) previously performed in the catchment area of the present tertiary referral centre. Time trends were analysed using the Cochrane-Armitage trend, Spearman's correlation coefficient and linear regression. RESULTS: In total, 195 patients undergoing ileocolic resection were included. Patient characteristics were not significantly different from the background cohort, confirming a representative study group. Sixty-three patients were men (32.3%, median age at surgery 30.0 years, interquartile range 23.0-40.0). Anti-TNF and immunomodulator use prior to surgery increased significantly during the study period (χ2 = 49.1, P < 0.001). Over the years, a significant increase in time from diagnosis to operation was found (median 39.0 months, interquartile range 12.0-86.0, rho 0.175, P = 0.014). The length of the resected ileum did not change significantly (median 20.0 cm, interquartile range 12.0-30.0, rho -0.107, P = 0.143). The number of fistulas or postoperative complications that needed re-intervention was not significantly different between the groups with or without anti-TNF. CONCLUSION: This study demonstrated that over time patients with ileocolic Crohn's disease who eventually underwent ileocolic resection have been treated more intensively medically; however, this did not result in reduced specimen size.
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Colectomia/estatística & dados numéricos , Doença de Crohn/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Colectomia/métodos , Colo/patologia , Colo/cirurgia , Terapia Combinada , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Íleo/patologia , Íleo/cirurgia , Fatores Imunológicos/uso terapêutico , Modelos Lineares , Masculino , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND AND AIMS: Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS: A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS: In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (7,905 [95% confidence interval 6,234 - 9,864] vs 6,017 [5,186 - 6,946] in never-smokers and 5,710 [4,687 - 6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years ( 5,135 [95% CI 4,122 - 6,303] vs 9,342 [6,010 - 12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS: Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.
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Colite Ulcerativa/economia , Colite Ulcerativa/epidemiologia , Efeitos Psicossociais da Doença , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Custos de Cuidados de Saúde , Qualidade de Vida , Fumar/economia , Fumar/epidemiologia , Adulto , Idoso , Colite Ulcerativa/tratamento farmacológico , Comorbidade , Doença de Crohn/tratamento farmacológico , Eficiência , Emprego/estatística & dados numéricos , Feminino , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Estudos Prospectivos , Índice de Gravidade de Doença , Abandono do Hábito de Fumar/economia , Inquéritos e Questionários , Exacerbação dos SintomasRESUMO
AIM: The introduction of anti-tumour necrosis factor (anti-TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti-TNF for Crohn's perianal fistula. METHOD: Studies evaluating the effect of setons and anti-TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end-point was the fistula closure rate. Partial closure and recurrence rates were secondary end-points. RESULTS: Ten studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti-TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0-91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti-TNF with placebo showed no significant difference in complete or partial closure in meta-analysis (risk difference 0.12, 95% CI -0.06 to 0.30 and 0.09, 95% CI -0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti-TNF in two trials with follow-up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014). CONCLUSION: Closure and recurrence rates after seton drainage as well as anti-TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti-TNF may be beneficial in achieving perianal fistula closure.
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Doença de Crohn/complicações , Drenagem/métodos , Fármacos Gastrointestinais/uso terapêutico , Fístula Retal/terapia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Períneo/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fístula Retal/etiologia , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Smoking affects the course of disease in patients with ulcerative colitis (UC) and Crohn's disease (CD). We aimed to study the association between smoking and extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: We cross-sectionally explored the association between smoking and EIMs in IBD in three cohort studies: (1) the COIN study, designed to estimate healthcare expenditures in IBD; (2) the Groningen study, focused on cigarette smoke exposure and disease behaviour in IBD; and (3) the JOINT study, evaluating joint and back manifestations in IBD. RESULTS: In the COIN, Groningen and JOINT cohorts, 3030, 797 and 225 patients were enrolled, of whom 16, 24 and 23.5% were current smokers, respectively. Chronic skin disorders and joint manifestations were more prevalent in smoking IBD patients than in non-smokers (COIN, 39.1 vs 29.8%, p <0.01; Groningen, 41.7 vs 30.0%, p <0.01) in both CD and UC. In the JOINT cohort, smoking was more prevalent in IBD patients with joint manifestations than in those without (30.3 vs 13.0%, p <0.01). EIMs appeared to be more prevalent in high- than in low-exposure smokers (56.0 vs 37.1%, p = 0.10). After smoking cessation, the prevalence of EIMs in IBD patients rapidly decreased towards levels found in never smokers (lag time: COIN cohort, 1-2 years; Groningen cohort, within 1 year). CONCLUSIONS: There is a robust dose-dependent association between active smoking and EIMs in both CD and UC patients. Smoking cessation was found to result in a rapid reduction of EIM prevalence to levels encountered in never smokers.
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Doenças Inflamatórias Intestinais/complicações , Fumar/efeitos adversos , Adulto , Artrite/etiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/etiologia , Colite Ulcerativa/patologia , Doença de Crohn/complicações , Doença de Crohn/etiologia , Doença de Crohn/patologia , Estudos Transversais , Feminino , Humanos , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Dermatopatias/etiologia , Abandono do Hábito de FumarRESUMO
MiR-511-3p is embedded in intron 5 of the CD206/MRC1 gene Mrc1, expressed by macrophage and dendritic cell populations. CD206 and miR-511-3p expression are co-regulated, and their contribution to intestinal inflammation is unclear. We investigated their roles in intestinal inflammation in both mouse and human systems. Colons of CD206-deficient mice displayed normal numbers of monocytes, macrophage, and dendritic cells. In experimental colitis, CD206-deficient mice had attenuated inflammation compared with wild-type (WT) mice. However, neither a CD206 antagonist nor a blocking antibody reproduced this phenotype, suggesting that CD206 was not involved in this response. Macrophages isolated from CD206-deficient mice had reduced levels of miR-511-3p and Tlr4 compared with WT, which was associated with reduced pro-inflammatory cytokine production upon lipopolysaccharides (LPS) and fecal supernatant stimulation. Macrophages overexpressing miR-511-3p showed 50% increase of Tlr4 mRNA, whereas knockdown of miR-511-3p reduced Tlr4 mRNA levels by 60%, compared with scrambled microRNA (miRNA)-transduced cells. Response to anti-tumor necrosis factor (TNF) treatment has been associated with elevated macrophage CD206 expression in the mucosa. However, in colon biopsies no statistically significant change in miR-511-3p was detected. Taken together, our data show that miR-511-3p controls macrophage-mediated microbial responses and is involved in the regulation of intestinal inflammation.
Assuntos
Colite/imunologia , Colo/imunologia , Macrófagos/imunologia , Glicoproteínas de Membrana/genética , MicroRNAs/genética , Receptores de Superfície Celular/genética , Animais , Células Cultivadas , Colite/induzido quimicamente , Sulfato de Dextrana , Feminino , Regulação da Expressão Gênica , Humanos , Lipopolissacarídeos/imunologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
OBJECTIVES: Randomized trials demonstrated that chromoendoscopy is superior to white light endoscopy with random biopsy sampling (WLE) for the detection of dysplasia in patients with inflammatory bowel disease (IBD). Whether implementing chromoendoscopy can increase the detection of dysplasia in clinical practice is unknown. METHODS: Patients with ulcerative colitis (UC) and Crohn's disease (CD) undergoing colonoscopic surveillance between January 2000 and November 2013 in three referral centers were identified using the patients' medical records. In recent years, the use of high-definition chromoendoscopy was adopted in all three centers using segmental pancolonic spraying of 0.1% methylene blue or 0.3% indigo carmine (chromoendoscopy group). Previously, surveillance was performed employing WLE with random biopsies every 10 cm (WLE group). The percentage of colonoscopies with dysplasia was compared between both groups. RESULTS: A total of 440 colonoscopies in 401 patients were performed using chromoendoscopy and 1,802 colonoscopies in 772 patients using WLE. Except for a higher number of CD patients with extensive disease and more patients with a first-degree relative with colorectal cancer (CRC) in the chromoendoscopy group, the known risk factors for IBD-associated CRC were comparable between both groups. Dysplasia was detected during 48 surveillance procedures (11%) in the chromoendoscopy group as compared with 189 procedures (10%) in the WLE group (P=0.80). Targeted biopsies yielded 59 dysplastic lesions in the chromoendoscopy group, comparable to the 211 dysplastic lesions detected in the WLE group (P=0.30). CONCLUSIONS: Despite compelling evidence from randomized trials, implementation of chromoendoscopy for IBD surveillance did not increase dysplasia detection compared with WLE with targeted and random biopsies.
Assuntos
Biópsia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etiologia , Detecção Precoce de Câncer/métodos , Doenças Inflamatórias Intestinais/complicações , Programas de Rastreamento/métodos , Vigilância da População/métodos , Adulto , Idoso , Colite Ulcerativa/complicações , Corantes , Doença de Crohn/complicações , Feminino , Humanos , Índigo Carmim , Masculino , Azul de Metileno , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Posterior rectal dissection during ileal pouch-anal anastomosis (IPAA) can be performed in the total mesorectal excision (TME) or close rectal dissection (CRD) plane. The aim of this study was to compare morbidity and quality of life (QoL) in patients having TME or CRD during proctectomy followed by IPAA for benign disease. METHODS: In this randomized clinical trial, patients undergoing IPAA were allocated to TME or CRD. Thirty-day morbidity was determined and QoL assessed using Short Form 36, GIQLI (GastroIntestinal Quality of Life Index) and COREFO (COloREctal Functional Outcome) questionnaires. The primary outcome (pouch compliance) of the trial is to be reported separately. RESULTS: Fifty-nine patients were included, 28 in the CRD and 31 in the TME group. Baseline data were similar, except for more previous abdominal surgery in the TME group. Operating time was longer for patients having CRD (195 min versus 166 min for TME; P = 0·008). More patients in the TME group had a primary defunctioning ileostomy (7 of 31 versus 1 of 28 for CRD; P = 0·055). Severe complications occurred more frequently in the TME group (10 of 31 versus 2 of 28 for CRD). QoL was better in the CRD group for several subscales of the questionnaires measured at 1, 3 and 6 months after surgery. At 12 months, QoL was similar in the two groups for all subscales. CONCLUSION: CRD led to a lower severe complication rate and better short-term QoL than wide TME.
Assuntos
Bolsas Cólicas , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Reto/cirurgia , Polipose Adenomatosa do Colo/cirurgia , Adulto , Canal Anal/cirurgia , Anastomose Cirúrgica/métodos , Feminino , Humanos , Doenças Inflamatórias Intestinais/cirurgia , Tempo de Internação , Masculino , Proctocolectomia Restauradora/métodos , Método Simples-Cego , Resultado do TratamentoRESUMO
AIM: The study aimed to determine the effectiveness and direct medical costs of early surgical closure of the anastomotic defect after a short course of Endo-sponge® therapy of the presacral cavity, compared with conventional treatment in patients with anastomotic leakage after ileal pouch-anal anastomosis (IPAA). METHOD: Patients with anastomotic leakage after IPAA undergoing early surgical closure of the anastomotic defect after a short Endo-sponge® treatment were prospectively followed and compared with a consecutive cohort of patients with an anastomotic leak treated by creation of a loop ileostomy and occasional drainage of the presacral cavity. RESULTS: A total of 15 patients were treated with early surgical closure and 29 were treated conventionally. In the early surgical closure group, the Endo-sponge® treatment was continued for a median of 12 days [interquartile range (IQR) 7-15 days] with a median of 3 (IQR 2-4) Endo-sponge® changes. Secondary anastomotic healing was achieved in all patients (n = 15) in the early surgical closure group compared with 52% (n = 16) in the conventional treatment group (P = 0.003). Closure of the anastomotic defect was achieved after a median of 48 (25-103) days in the early surgical closure group compared with 70 (IQR 49-175) days in the conventional treatment group (P = 0.013). A functional pouch was seen in 93% and 86% of the patients in each group. There was no significant difference in direct medical cost. CONCLUSION: Early surgical closure after a short period of Endo-sponge® treatment is highly effective in treating anastomotic leakage after IPAA without increasing cost.
Assuntos
Polipose Adenomatosa do Colo/cirurgia , Fístula Anastomótica/cirurgia , Colite Ulcerativa/cirurgia , Bolsas Cólicas , Ileostomia/métodos , Proctocolectomia Restauradora/métodos , Adulto , Anastomose Cirúrgica/métodos , Estudos de Coortes , Intervenção Médica Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento de Ferimentos com Pressão Negativa/métodos , Estudos Prospectivos , Reoperação , Estudos Retrospectivos , Adulto JovemRESUMO
AIM: Risk factors for postoperative complications in patients undergoing emergency colectomy for severe colitis in inflammatory bowel disease have hardly been studied. Therefore, this study aimed to define predictors of a complicated postoperative course in these patients. METHOD: A retrospective review was performed of 71 consecutive patients who underwent emergency colectomy for severe colitis between 1999 and 2012 at a tertiary referral centre. Complications were graded according to the Clavien-Dindo classification. Patients with a complication Grade II or higher were compared with those with no complications or a Grade I complication. RESULTS: Nineteen patients (26.7%) had at least one postoperative complication classified as Clavien-Dindo Grade II or higher. In the group with postoperative complications, patients had a higher age (mean 45 vs 35 years, P = 0.020) and a higher body mass index (BMI) (mean 25.9 vs 21.0 kg/m(2), P = 0.006). Length of preoperative hospital stay (median 15 vs 6 days, P = 0.032) was longer in the group with postoperative complications. During the study period, the preoperative hospital stay decreased by 0.8 days per study year (95% CI 0.2-1.5 days, P < 0.001). This did not influence the complication rate over time, however. CONCLUSION: Factors increasing the risk of complications after emergency colectomy for severe colitis were a higher age, a higher BMI and a longer preoperative hospital stay.