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2.
BMC Gastroenterol ; 19(1): 5, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621600

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.


Assuntos
Doenças Inflamatórias Intestinais/classificação , Doenças Inflamatórias Intestinais/genética , Adolescente , Adulto , Idoso , Biomarcadores , Biópsia , Dieta , Meio Ambiente , Feminino , Microbioma Gastrointestinal , Genótipo , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Transcriptoma , Sequenciamento do Exoma , Adulto Jovem
3.
Ann Surg Oncol ; 24(7): 1828-1834, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28303427

RESUMO

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. METHODS: During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid 18F-FDG-PET/CT or 18F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. RESULTS: EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. CONCLUSIONS: EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes.


Assuntos
Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Endossonografia/métodos , Neoplasias Esofágicas/patologia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Idoso , Biópsia por Agulha Fina , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Gut ; 65(9): 1505-13, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-25986944

RESUMO

OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.


Assuntos
Carcinoma Ductal Pancreático , Endossonografia , Imageamento por Ressonância Magnética , Pâncreas/diagnóstico por imagem , Cisto Pancreático , Neoplasias Pancreáticas , Adulto , Doenças Assintomáticas , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Estudos de Coortes , Pesquisa Comparativa da Efetividade/métodos , Detecção Precoce de Câncer/métodos , Endossonografia/métodos , Endossonografia/estatística & dados numéricos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos , Pâncreas/patologia , Cisto Pancreático/diagnóstico , Cisto Pancreático/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Estudos Prospectivos
5.
Ann Surg Oncol ; 23(Suppl 5): 1021-1028, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-21547703

RESUMO

BACKGROUND: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. METHODS: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. RESULTS: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. CONCLUSIONS: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Tomografia por Emissão de Pósitrons , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Fluordesoxiglucose F18 , Humanos , Funções Verossimilhança , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Período Pré-Operatório , Estudos Prospectivos , Compostos Radiofarmacêuticos
6.
Pancreatology ; 15(1): 46-52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25511908

RESUMO

BACKGROUND: Chronic pancreatitis is a complex disease with many unanswered questions regarding the natural history and therapy. Prospective longitudinal studies with long-term follow-up are warranted. METHODS: The Dutch Chronic Pancreatitis Registry (CARE) is a nationwide registry aimed at prospective evaluation and follow-up of patients with chronic pancreatitis. All patients with (suspected) chronic or recurrent pancreatitis are eligible for CARE. Patients are followed-up by yearly questionnaires and review of medical records. Study outcomes are pain, disease complications, quality of life, and pancreatic function. The target sample size was set at 500 for the first year and 1000 patients within 3 years. RESULTS: A total of 1218 patients were included from February 2010 until June 2013 by 76 participating surgeons and gastroenterologist from 33 hospitals. Participation rate was 90% of eligible patients. Eight academic centers included 761 (62%) patients, while 25 community hospitals included 457 (38%). Patient centered outcomes were assessed by yearly questionnaires, which had a response rate of 85 and 82% for year 1 and 2, respectively. The median age of patients was 58 years, 814 (67%) were male, and 38% had symptoms for less than 5 years. DISCUSSION: The CARE registry has successfully recruited over 1200 patients with chronic and recurrent pancreatitis in about 3 years. The defined inclusion criteria ensure patients are included at an early disease stage. Participation and compliance rates are high. CARE offers a unique opportunity with sufficient power to investigate many clinical questions regarding natural course, complications, and efficacy and timing of treatment strategies.


Assuntos
Pancreatite Crônica , Sistema de Registros , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Avaliação de Resultados em Cuidados de Saúde , Medição da Dor , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
7.
Neth J Med ; 68(9): 360-4, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20876916

RESUMO

BACKGROUND: In the assessment of patients with a clinical suspicion of malignant pancreatic disease, computed tomography (CT) findings are sometimes negative or inconclusive. AIMS: To determine whether endoscopic ultrasonography (EUS) with or without fine needle aspiration (EUS÷FNA) was conclusive in patients with a clinical suspicion of pancreatic malignancy, in whom CT scan was negative or inconclusive. METHODS: Retrospective case series in a tertiary referral centre. From February 2006 to December 2007, EUS÷FNA was performed in all patients suspected of having malignant pancreatic disease with negative or inconclusive CT findings. Main outcome measurement was the diagnostic yield of EUS in these patients. RESULTS: 34 patients had a negative (n=11) or inconclusive (n=23) CT scan. EUS÷FNA established a correct diagnosis in 30÷34 cases (88%). Malignancy was diagnosed in 19÷34 patients and nonmalignant disease in 8÷34 cases. In 3÷34 patients no lesions were found and no malignant disease developed during follow-up (mean=728 days). EUS÷FNA was inconclusive in 4÷34 patients. CONCLUSION: In patients with a clinical suspicion of pancreatic malignancy with negative or inconclusive CT findings, EUS÷FNA was able to establish a diagnosis in 88% of cases. EUS should therefore be considered a diagnostic modality in this complex group of patients.


Assuntos
Endossonografia/instrumentação , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Adulto Jovem
8.
Cancer Imaging ; 9: 19-28, 2009 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-19414293

RESUMO

AIM: In this feasibility study we investigated whether magnetic resonance imaging (MRI) with ultrasmall superparamagnetic iron oxide (USPIO) can be used to identify regional and distant lymph nodes, including mediastinal and celiac lymph node metastases in patients with oesophageal cancer. PATIENTS AND METHODS: Ten patients with a potentially curative resectable cancer of the oesophagus were eligible for this study. All patients included in the study had positive lymph nodes on conventional staging (including endoscopic ultrasound, computed tomography and fluorodeoxyglucose-positron emission tomography). Nine patients underwent MRI + USPIO before surgery. Results were restricted to those patients who had both MRI + USPIO and histological examination. Results were compared with conventional staging and histopathologic findings. RESULTS: One patient was excluded due to expired study time. Five out of 9 patients underwent an exploration; in 1 patient prior to surgery MRI + USPIO diagnosed liver metastases and in 3 patients an oesophageal resection was performed. USPIO uptake in mediastinal lymph nodes was seen in 6 out of 9 patients; in 3 patients non-malignant nodes were not visible. In total, 9 lymph node stations (of 6 patients) were separately analysed; 7 lymph node stations were assessed as positive (N1) on MRI+USPIO compared with 9 by conventional staging. According to histology findings, there was one false-positive and one false-negative result in MRI + USPIO. Also, conventional staging modalities had one false-positive and one false-negative result. MRI + USPIO had surplus value in one patient. Not all lymph node stations could be compared due to unforeseen explorations. No adverse effects occurred after USPIO infusion. CONCLUSION: MRI+USPIO identified the majority of mediastinal and celiac (suspect) lymph nodes in 9 patients with oesophageal cancer. MRI+USPIO could have an additional value in loco-regional staging; however, more supplementary research is needed.


Assuntos
Meios de Contraste , Neoplasias Esofágicas/patologia , Ferro , Imageamento por Ressonância Magnética/métodos , Óxidos , Idoso , Dextranos , Neoplasias Esofágicas/cirurgia , Estudos de Viabilidade , Feminino , Óxido Ferroso-Férrico , Humanos , Aumento da Imagem , Metástase Linfática , Nanopartículas de Magnetita , Masculino , Pessoa de Meia-Idade
10.
Ned Tijdschr Geneeskd ; 152(18): 1037-41, 2008 May 03.
Artigo em Holandês | MEDLINE | ID: mdl-18547024

RESUMO

--Cholangiocarcinoma is a rare malignancy originating from the biliary epithelium. The disease can arise anywhere in the biliary tract: intrahepatic, perihilar or distal. The overall prognosis for cholangiocarcinoma is poor. --The treatment necessitates a multidisciplinary approach. --Radical resection of the extrahepatic bile ducts, usually in combination with concomitant partial liver resection, remains the only curative treatment. --Liver transplantation in combination with neoadjuvant chemoradiation therapy seems to be promising in a highly selected group of patients. --Palliative treatment should be targeted at adequate biliary drainage, preferably by stenting. --Radiotherapy and systemic chemotherapy are not standard treatment and should be applied in an experimental setting only. --New options such as photodynamic therapy and tyrosine kinase inhibitors are promising, but still experimental treatments.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangiocarcinoma/diagnóstico , Transplante de Fígado , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/terapia , Terapia Combinada , Humanos , Cuidados Paliativos , Prognóstico , Resultado do Tratamento
11.
Endoscopy ; 40(6): 464-71, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18543134

RESUMO

BACKGROUND AND STUDY AIMS: To assess the prognostic importance of standardized uptake value (SUV) for 18F-fluorodeoxyglucose (FDG) at positron emission tomography (PET) and of EUS parameters, in esophageal cancer patients primarily treated by surgery. PATIENTS AND METHODS: Between October 2002 and August 2004 a prospective cohort study involved 125 patients, with histologically proven cancer of the esophagus, without evidence of distant metastases or locally irresectable disease based on extensive preoperative work-up, and fit to undergo major surgery. Follow-up was complete until October 2006, ensuring a minimal potential follow-up of 25 months. RESULTS: The median SUV was 0.27 (interquartile range 0.13 - 0.45), and was used as cutoff value between high (n = 62) and low (n = 63) SUV. Patients with a high SUV had a significantly worse disease-specific survival compared with patients with a low SUV (P = 0.04). Tumor location (P = 0.005), EUS T stage (P < 0.001), EUS N stage (P = 0.006) and clinical stage (P < 0.006) were also associated with disease-specific survival. However, in multivariate analysis only EUS T stage appeared to be of independent prognostic significance (P = 0.007). CONCLUSION: In esophageal cancer patients, EUS T stage, EUS N stage, location and SUV of the primary tumor are pretreatment factors that are associated with disease-specific survival. However, only EUS T stage is an independent prognostic factor.


Assuntos
Endossonografia/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/mortalidade , Estadiamento de Neoplasias/métodos , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Biópsia por Agulha , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagectomia/mortalidade , Feminino , Fluordesoxiglucose F18 , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Probabilidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento
12.
Dis Esophagus ; 21(4): 334-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18477256

RESUMO

We aim to determine the effect of splenectomy on clinical outcome in patients with cancer of the distal esophagus and gastro-esophageal junction (GEJ) after a curative intended resection. From January 1991 to July 2004, 210 patients underwent a potentially curative gastroesophageal resection with an extended nodal dissection. The study group was divided into: group I with splenectomy, consisting of 66 patients (31.4%), and group II without splenectomy, of 144 patients. Splenectomy was performed for oncological reasons. Medical records were reviewed retrospectively. Postoperative complications occurred in 27 patients (40.9%) in group I and in 68 patients (47.2%) in group II (P = 0.4). The overall mortality was not significantly different between both groups (P = 0.7). There was a higher administration of red blood cells during surgery (P < or = 0.001), increased operating room (OR) time (P < or = 0.001) and longer intensive care unit (ICU) stay (P = 0.01) in group I. Independent prognostic factors for survival were outcome of surgery, nodal metastases, gender, complications and ICU stay. Sepsis was a strong prognostic factor among the complications. The 1 and 2-year survival was significantly higher in group II; 75% and 67% (P = 0.032) compared to 69% and 56% (P = 0.017) in group I, respectively. However, the 5-year survival was not different in both groups (29% in group I and 60% in group II, P = 0.191). Splenectomy had no marked effect on mortality and morbidity after curative resection of esophageal cancer. Splenectomy had a significant increase in blood transfusions with prolonged OR time and ICU stay and decreased short-term survival.


Assuntos
Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica , Esplenectomia , Adulto , Idoso , Neoplasias Esofágicas/mortalidade , Esofagectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Mortalidade , Prognóstico , Estudos Retrospectivos , Esplenectomia/estatística & dados numéricos , Análise de Sobrevida
13.
Neth J Med ; 65(10): 368-71, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18057458

RESUMO

BACKGROUND: Spontaneous pneumomediastinum has been infrequently reported as a complication of diabetic ketoacidosis. Evidence-based guidelines are currently not available to help in choosing the best diagnostic approach. METHODS: We conducted a systematic review of the literature and looked for diagnostic clues that might indicate the need for a work-up to rule out oesophageal perforation. RESULTS: In all 56 published cases of spontaneous pneumomediastinum associated with diabetic ketoacidosis, the condition was self-limiting. We report one additional case of a 31-year-old female who presented with a spontaneous pneumomediastinum and also epidural pneumatosis, complicating diabetic ketoacidosis. CONCLUSION: Important pathology, such as oesophageal rupture, was not detected in any of the reported cases, and we suggest a restrictive diagnostic work-up.


Assuntos
Cetoacidose Diabética/fisiopatologia , Enfisema Mediastínico/diagnóstico , Enfisema Mediastínico/fisiopatologia , Adulto , Cetoacidose Diabética/complicações , Cetoacidose Diabética/diagnóstico , Feminino , Humanos , Enfisema Mediastínico/complicações , Enfisema Mediastínico/etiologia
14.
Br J Surg ; 94(12): 1515-20, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17902092

RESUMO

BACKGROUND: The detection of distant metastases in patients with oesophageal cancer may be improved with [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), preventing unnecessary surgical explorations. The aim of this study was to assess the additional value of FDG-PET after a state-of-the-art preoperative staging protocol. METHODS: All patients in this prospective cohort study were staged with multidetector computed tomography, endoscopic ultrasonography and external ultrasonography of the neck, both combined with selective fine-needle aspiration cytology. Patients considered eligible for curative surgery after these investigations underwent FDG-PET. RESULTS: FDG-PET revealed suspicious hot spots in 30 (15.1 per cent) of 199 patients. Metastases were confirmed in eight (4.0 per cent). In six of these, distant metastases were confirmed before surgery, but exploratory surgery was necessary for histological confirmation in the other two. All eight upstaged patients had clinical stage III-IV disease before FDG-PET (6.6 per cent of 122 with stage III-IV disease). In seven patients (3.5 per cent) hot spots appeared to be synchronous neoplasms, mainly colonic polyps. However, those in the remaining 15 (7.5 per cent) were false positive, leading to unnecessary additional investigations. CONCLUSION: FDG-PET improves the selection of patients with oesophageal cancer for potentially curative surgery, especially in stages III-IV. However, the diagnostic benefit is limited after state-of-the-art staging, and so broad implementation in daily clinical practice is questionable.


Assuntos
Neoplasias Esofágicas/patologia , Fluordesoxiglucose F18 , Metástase Neoplásica/patologia , Compostos Radiofarmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Estadiamento de Neoplasias/métodos , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos
15.
Aliment Pharmacol Ther ; 26 Suppl 2: 57-65, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18081650

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn's disease (CD) is multigenic disorder. Tremendous progress has been achieved in unravelling the genetic background of IBD. It has led to the discovery of mutations in NOD2 associated with ileal CD and numerous other genes have been found to be associated with IBD susceptibility. METHODS: A review of the literature on the genetic background of IBD was performed. RESULTS: It is only partially understood how mutations in NOD2 lead to CD. Mouse models, in vitro data and studies in humans offer conflicting data as regards whether there is a loss or gain of function of NOD2 in CD. Several additional genes have been identified of which only a few are currently being recognized as potential disease causing or disease modifying genes. Promising candidate genes include TLR4, MDR1, NOD1 (CARD4), DLG5 as well as the IBD5 locus including SLC22A4/5. CONCLUSIONS: Although genetic research has not yet led to a better prediction of the disease course or patient selection for medical therapy, remarkable progress has been made in the understanding of the pathogenesis of IBD. For future genetic research, accurate phenotyping of patients is very important and large population-based cohorts are needed. Eventually, genetic research may be able to classify different disease phenotypes on a more detailed molecular basis and may provide important contributions in the development of new therapeutic approaches.


Assuntos
Predisposição Genética para Doença/genética , Doenças Inflamatórias Intestinais/genética , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD2/genética , Receptor 4 Toll-Like/genética , Humanos
16.
Scand J Gastroenterol Suppl ; (243): 55-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16894670

RESUMO

Treatment strategies for Crohn's disease are targeted toward lifelong management. Optimization of outpatient care is mandatory, because of many clinics facing capacity issues, and, along with routine follow-up of patients with inflammatory bowel disease, is putting increasing pressure on outpatient clinics. Recent studies demonstrate clearly that alternative management strategies are feasible and effective with a high rate of patient satisfaction. It is recommended that future research evaluates the way in which medical care is provided and explores the long-term effects of novel management strategies in IBD. This approach can then be extrapolated to other chronic conditions.


Assuntos
Assistência Ambulatorial , Doenças Inflamatórias Intestinais/terapia , Colite Ulcerativa/terapia , Doença de Crohn/terapia , Humanos , Satisfação do Paciente
17.
Dig Liver Dis ; 38(11): 834-45, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16920047

RESUMO

BACKGROUND: Three major polymorphisms of the Caspase-Activation Recruitment Domain containing protein 15 gene have been described to be associated with Crohn's disease. Genotype-phenotype studies reported in literature provide conflicting data on disease localisation and behaviour. We investigated the relation of Caspase-Activation Recruitment Domain containing protein 15 with inflammatory bowel disease and Crohn's disease phenotypic characteristics in a large Dutch cohort and performed a pooled analysis on inflammatory bowel disease patients and Crohn's disease phenotypic characteristics reported in association studies. METHODS: We genotyped 781 cases and 315 controls for the R702W, G908R and 1007fsinsC variants and for six microsatellite markers in and close to Caspase-Activation Recruitment Domain containing protein 15. In the pooled analysis data of 7201 inflammatory bowel disease patients and 3720 controls from 20 studies were included. RESULTS: Association was found for Crohn's disease with R702W and 1007fsinsC, including several disease characteristics, and not for ulcerative colitis. In the pooled analysis all three common Caspase-Activation Recruitment Domain containing protein 15 variants showed strong association with Crohn's disease (p<0.00001; odds ratio varying from 3.0 for single heterozygotes to 14.7 for compound heterozygotes) and not with ulcerative colitis. Phenotype analysis showed association with small bowel involvement, stricturing and penetrating disease. CONCLUSION: Caspase-Activation Recruitment Domain containing protein 15 is associated with Crohn's disease and not with ulcerative colitis. All three common Crohn's disease-associated variants are associated with small bowel involvement, the G908R and 1007fsinsC alleles also being associated with a complicated disease course.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Proteína Adaptadora de Sinalização NOD2/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Polimorfismo de Nucleotídeo Único
18.
Scand J Gastroenterol Suppl ; (243): 39-45, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16782621

RESUMO

Intestinal transplantation for intestinal failure is no longer an experimental procedure, but an accepted treatment for patients who fail total parenteral nutrition (TPN) therapy. Early referral for evaluation for small bowel transplantation has to be considered in patients with permanent intestinal failure who have occlusion of more than two major veins, frequent line-related septic episodes, impairment of liver function or an unacceptable quality of life. With the increased experience in post-transplant patient care and newer forms of induction (thymoglobulin, IL-2 receptor antagonists) and maintenance (tacrolimus) therapies the 1-year graft survival has increased to 65% for isolated and to 59% for liver/small bowel transplantation, and is further improving. Rejection, bacterial, fungal and viral (CMV, EBV) infection, post-transplant lymphoproliferative disease (PTLD) and graft versus host disease (GvHD) are the most common complications after intestinal transplantation. Although most of the long-term survivors are TPN-independent and have a good quality of life, the risk of the procedure and long-term adverse effects of immunosuppressive medication limits small bowel, or liver/small bowel transplantation only to patients with severe complications of TPN therapy.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/tendências , Intestino Delgado/transplante , Adulto , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Imunossupressores/uso terapêutico , Enteropatias/cirurgia , Intestino Delgado/irrigação sanguínea , Intestino Delgado/patologia , Pessoa de Meia-Idade , Países Baixos , Nutrição Parenteral Total
19.
Scand J Gastroenterol Suppl ; (243): 158-64, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16782636

RESUMO

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.


Assuntos
Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Fatores Etários , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Neoplasias do Colo/etiologia , Neoplasias do Colo/prevenção & controle , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Europa (Continente)/epidemiologia , Ácido Fólico/administração & dosagem , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Vigilância da População , Fatores de Risco , Fatores Sexuais
20.
Ned Tijdschr Geneeskd ; 150(1): 12-7, 2006 Jan 07.
Artigo em Holandês | MEDLINE | ID: mdl-16440618

RESUMO

10-15% of patients with ulcerative colitis experience a severe episode of colonic inflammation that does not respond to mesalazine and oral corticosteroids. These patients require hospitalisation and treatment with intravenous corticosteroids. However, 25% of these patients do not respond to treatment. In these cases, intravenous cyclosporin is effective. Infliximab, an antibody against tumour necrosis factor alpha, is also beneficial. With these new treatment options, the colectomy rate in the acute phase has declined to about 35%. Other new therapies are under investigation in phase 2 and 3 trials. Surgery remains an important treatment option. Patients, gastroenterologists and surgeons should be involved in the clinical decision-making process.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Corticosteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/cirurgia , Ciclosporina/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab , Administração dos Cuidados ao Paciente , Indução de Remissão
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