RESUMO
BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.
Assuntos
Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/mortalidade , Neoplasias/complicações , Neoplasias/mortalidade , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Neoplasias/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
Until 1998, intestinal transplantation (SBT) had not been performed in our region of Flanders, Belgium. Potential SBT activity was not known and selection criteria had not been validated. A multidisciplinary SBT program was launched in 1998. We analyzed requests for SBT and outcomes in these patients whether with or without SBT. Listing for SBT was only considered for patients with irreversible short bowel syndrome who had developed life-threatening complications of total parenteral nutrition, but whose general condition was still thought compatible with surgery and immunosuppression. During the study period 1998 to 2004, one third of the requests for SBT (10/31) were deemed suitable. SBT in this group was lifesaving (100% survival) when performed in time. Mortality in this group without SBT was high (67%). Two thirds of the patients (21/31) did not fulfill the SBT inclusion criteria, either because they were "too moribund" to tolerate transplantation or because they were "too well". This preliminary study emphasized the importance of (1) early referral of potential SBT candidates, (2) adherence to strict criteria for listing patients for SBT, and (3) referral of intestinal donors to procurement organizations.
Assuntos
Intestino Delgado/transplante , Adulto , Criança , Europa (Continente) , Humanos , Nutrição Parenteral Total , Seleção de Pacientes , Transplante Homólogo/fisiologia , Resultado do TratamentoRESUMO
BACKGROUND: (99m) Technetium scintigraphy ((99m) TS) is the 'gold standard' for measuring gastric emptying (GE), but it is associated with a radiation exposure. For this reason, the (13) C-octanoic acid breath test ((13) C-OBT) was developed for measuring GE of solids. The objective of this study was to determine normal values for gastric half-emptying time (t1/2 GE) of solids in healthy children. METHODS: Gastric emptying of a standardized solid test meal consisting of a pancake evaluated with (99m) TS and (13) C-OBT was compared in 22 children aged between 1 and 15 years with upper gastrointestinal symptoms. Subsequently, the (13) C-OBT was used to determine normal values for GE of the same solid test meal in 120 healthy children aged between 1 and 17 years. KEY RESULTS: The results showed a significant correlation (r = 0.748, p = 0.0001) between t1/2 GE measured with both techniques in the group of children with upper gastrointestinal symptoms. In the group of healthy children, mean t1/2 GE was 157.7 ± 54.0 min (range 71-415 min), but t1/2 GE decreased with age between 1 and 10 years and remained stable afterward. There was no influence of gender, weight, height, body mass index, and body surface area on t1/2 GE. CONCLUSIONS & INFERENCES: Normal values for GE of solids measured with the (13) C-OBT using a standardized methodology were determined in healthy children. We propose to use this method and corresponding reference ranges to study GE of solids in children with gastrointestinal problems.
Assuntos
Caprilatos/análise , Isótopos de Carbono/análise , Esvaziamento Gástrico/fisiologia , Refeições/fisiologia , Adolescente , Testes Respiratórios/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Padrões de Referência , Espectrofotometria Infravermelho/métodosRESUMO
Liver metastases in colorectal cancer patients decreases the expected 5 year survival rates by a factor close to nine. It is generally accepted that resection of liver metastases should be attempted whenever feasible. This manuscript addresses the optimal therapeutic plan regarding timing of resection of synchronous liver metastases and the use of chemotherapy in combination with resection of synchronous metachronous liver metastases. The aim is to pool all published results in order to attribute a level of evidence to outcomes and identify lacking evidence areas. A systematic search of guidelines, reviews, randomised controlled, observational studies and updating a meta-analysis was performed. Data were extracted and analysed. Data failed to demonstrate an effect of timing of surgery or use of chemotherapy on overall survival. Concomitant resection of liver metastases and the primary tumour may result in lower postoperative morbidity. Systemic peri-operative chemotherapy may improve progression free survival compared to surgery alone.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/diagnóstico , Terapia Combinada/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Gradação de Tumores , Estadiamento de Neoplasias , Fatores de Tempo , Resultado do TratamentoRESUMO
While the role of microflora is well established in the development of inflammatory bowel disease (IBS); data is still emerging regarding IBS as the knowledge on brain-gut interaction grows. For both patient groups multiple efficacious treatments exist, but there are still unmet needs as long term disease control remains an issue. Given the importance of the microbiome on the development of the immune system and the interaction between the microbiome and the host organism, this "route" is being examined increasingly as a therapeutic possibility in both pathologies with variable results. We here provide a short overview on the existing data, meta-analysis and single studies, on probiotic treatment in both diseases.
Assuntos
Trato Gastrointestinal/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Probióticos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Medicina Baseada em Evidências , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/microbiologia , Metanálise como Assunto , Resultado do TratamentoRESUMO
Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
Assuntos
Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Doença de Crohn/terapia , Nutrição Enteral , Imunossupressores/uso terapêutico , Quimioterapia de Manutenção/métodos , Indução de Remissão/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adolescente , Corticosteroides/efeitos adversos , Algoritmos , Ácidos Aminossalicílicos/uso terapêutico , Antibacterianos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Azatioprina/uso terapêutico , Criança , Humanos , Infliximab , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Talidomida/uso terapêuticoRESUMO
INTRODUCTION: Magnetic Resonance enterography (MRE) is an imaging modality avoiding ionizing radiation and the discomfort associated with enteroclysis. The results of MRE at diagnosis in the patients of the Belgian pediatric Crohn registry (Belcro) are compared to endoscopical and histological results. METHODS: Results of MRE, endoscopy and histology were obtained from the medical charts and assigned to one of the following segments: jejunum, ileum, ascending colon, transverse colon, descending colon or rectosigmoid. MRE images were reviewed in a blinded way by 4 radiologists with specific interest in pediatric MRE. RESULTS: From the Belcro registry, twenty-two patients underwent a MRE during their work-up for Crohn disease. The results of endoscopy, histology and MRE were concordant (either all negative or positive) in the ileum in 16/18 patients and in the rectosigmoid, descending colon, transverse colon and ascending colon in resp 9, 8, 8 and 8/22 patients. In the non-concordant cases (MRE colon negative but endoscopy and/or histology positive), MRE could not reflect the subtle endoscopic or histologic lesions such as erosions that were described.In 4 cases where ileocaecal valve intubation was impossible ileal MRE findings were abnormal. MRE detected ileal stenosis, jejunal lesions and fistula in resp 4/22, 3/22 en 2/22 patients. The 100% and 75% interobserver agreement was resp 50-82% and 773-100% according to the different intestinal segments. CONCLUSIONS: MRE is a promising imaging modality avoiding radiation in Crohn disease. It should probably become the technique of first choice for the evaluation of extensive small bowel disease in children with Crohn disease.
Assuntos
Doença de Crohn/patologia , Endoscopia Gastrointestinal/métodos , Intestinos/patologia , Imageamento por Ressonância Magnética/métodos , Sistema de Registros , Adolescente , Bélgica , Criança , Endoscopia Gastrointestinal/estatística & dados numéricos , Feminino , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Variações Dependentes do ObservadorRESUMO
AIM: A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. METHODS: Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. RESULTS: Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. CONCLUSION: In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice.
Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Sistema de Registros , Adolescente , Distribuição por Idade , Idade de Início , Anti-Inflamatórios/uso terapêutico , Bélgica/epidemiologia , Criança , Pré-Escolar , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Quimioterapia Combinada , Humanos , Imunossupressores , Lactente , Modelos Logísticos , Monitorização Fisiológica/métodos , Análise Multivariada , Prevalência , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não ParamétricasRESUMO
Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD.
Assuntos
Anticorpos Monoclonais , Doença de Crohn , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/economia , Bélgica/epidemiologia , Criança , Efeitos Psicossociais da Doença , Doença de Crohn/tratamento farmacológico , Doença de Crohn/economia , Doença de Crohn/epidemiologia , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/economia , Humanos , Infliximab , Infusões Intravenosas , Masculino , Conduta do Tratamento Medicamentoso , Farmacovigilância , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: TPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). However, in one previous study, only about » of MS episodes in Crohn's Disease patients under AZA can be attributed to TPMT deficiency. Recently, new TPMT mutations have been described and our aim is to investigate their clinical relevance before and after a first MS episode on thiopurine therapy. METHODS: Clinical data from 61 IBD patients having developed MS during AZA therapy were collected. Sequencing analysis was carried out on TPMT cDNA for the presence of all currently known mutations. RESULTS: Only TPMT *2, *3A and *3C mutations were found in this cohort. TPMT mutations were observed in 15 out of 61 patients (25%). Four out of 15 were homozygous for a TPMT mutation (low methylator, LM genotype) and 11 were heterozygous (intermediate methylator, IM genotype). Median delays of MS onset were 2, 2.75 and 6months in the LM, IM and HM (high methylator, wild type TPMT) groups, respectively. After the first MS episode, 36 patients resumed thiopurine treatment of which 13 experienced a second MS episode. This second episode was also rarely associated with TPMT mutations. CONCLUSIONS: One quarter of MS episodes during AZA were associated with TPMT deficient genotype. After a first leucopenia episode, thiopurine therapy may be resumed in a majority of patients independently of their TPMT genotype.
Assuntos
Azatioprina/efeitos adversos , Hipersensibilidade a Drogas/complicações , Doenças Inflamatórias Intestinais/complicações , Metiltransferases/genética , Erros Inatos do Metabolismo da Purina-Pirimidina/complicações , Adolescente , Adulto , Idoso , Azatioprina/uso terapêutico , Análise Mutacional de DNA , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/genética , Feminino , Genótipo , Humanos , Imunossupressores , Doenças Inflamatórias Intestinais/tratamento farmacológico , Leucopenia , Masculino , Pessoa de Meia-Idade , Mutação , Pancitopenia/induzido quimicamente , Pancitopenia/genética , Erros Inatos do Metabolismo da Purina-Pirimidina/etiologia , Erros Inatos do Metabolismo da Purina-Pirimidina/genética , Estudos Retrospectivos , Adulto JovemAssuntos
Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Gastroenterologia , Padrões de Prática Médica , Adolescente , Adulto , Fatores Etários , Bélgica , Criança , Feminino , Humanos , MasculinoRESUMO
In 61 cystic fibrosis (CF) patients, the small intestinal mucosa was studied at the time of diagnosis before starting therapy. In 19 out of 61 patients, partial villous atrophy on light microscopy and shortened villi on stereomicroscopic examination were seen. On the biopsy specimens, maltase, sucrase, lactase and alkaline phosphatase activities were studied. Comparison of the enzymatic activities in CF patients having damaged mucosa and a group of patients having similar mucosal lesions of unspecified origin (UTID), reveals a significantly more pronounced decrease of the alkaline phosphatase activity (p < 0.005) in the CF patients. This is in agreement with previous reported results in CF patients with normal mucosa. The abnormal mucosal findings could be due to the decreased neutralization of the gastric content delivered into the duodenum, the early inflammatory reaction present in the CF mucosa and/or to the impaired synthesis of membrane glycoproteins and enzymes secondary to the CFTR mutation.
Assuntos
Fibrose Cística/enzimologia , Fibrose Cística/patologia , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Intestino Delgado/enzimologia , Biópsia por Agulha , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Ativação Enzimática , Feminino , Humanos , Imuno-Histoquímica , Lactente , Intestino Delgado/patologia , Lactase/metabolismo , Masculino , Microvilosidades , Probabilidade , Prognóstico , Valores de Referência , Sacarase/metabolismo , alfa-Glucosidases/metabolismoRESUMO
The study concerns the maltase, saccharase, lactase and alkaline phosphatase activity in small intestinal biopsy specimens from 61 consecutively admitted, untreated, Caucasian cystic fibrosis patients. A group of 319 age matched controls admitted during the same time period for undefined gastrointestinal or nutritional disorders acted as the controls. In order to eliminate morphological damage as a confounding factor, the enzyme activities were studied in small intestinal biopsy specimens having both normal stereomicroscopic and histological features. It was shown that neither maltase nor saccharase activity was different in the two groups, in contrast to lactase and alkaline phophatase activity, that was significantly lower in cystic fibrosis patients. The differences could not be explained by the nutritional status as judged by the body mass index. Lactase activity is known to be easily affected by numerous enteropathies. As the information on alkaline phosphatase activity is limited, the low activity is discussed in more detail. Taking into account the literature data, the low alkaline phosphatase activity is tentatively attributed either to enhanced release from the brush border or to the faulty handling of alkaline phophatase protein in the post-golgi compartments secondary to the accumulation of incorrectly glycosylated CFTR in the same cell structures.