RESUMO
BACKGROUND AND AIMS: For a highly selected group of patients with unresectable perihilar cholangiocarcinoma (pCCA), liver transplantation (LT) is a treatment option. The Dutch screening protocol comprises nonregional lymph node (LN) assessment by EUS, and whenever LN metastases are identified, further LT screening is precluded. The aim of this study is to investigate the yield of EUS in patients with pCCA who are potentially eligible for LT. METHODS: In this retrospective, nationwide cohort study, all consecutive patients with suspected unresectable pCCA who underwent EUS in the screening protocol for LT were included from 2011 to 2021. During EUS, sampling of a "suspicious" nonregional LN was performed based on the endoscopist's discretion. The primary outcome was the added value of EUS, defined as the number of patients who were precluded from further screening because of malignant LNs. RESULTS: A total of 75 patients were included in whom 84 EUS procedures were performed, with EUS-guided tissue acquisition confirming malignancy in LNs in 3 of 75 (4%) patients. In the 43 who underwent surgical staging according to the protocol, nonregional LNs with malignancy were identified in 6 (14%) patients. Positive regional LNs were found in 7 patients in post-LT-resected specimens. CONCLUSIONS: Our current EUS screening for the detection of malignant LNs in patients with pCCA eligible for LT shows a limited but clinically important yield. EUS with systematic screening of all LN stations, both regional and nonregional, and the sampling of suspicious lymph nodes according to defined and set criteria could potentially increase this yield.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Transplante de Fígado , Humanos , Estudos de Coortes , Estudos Retrospectivos , Tumor de Klatskin/diagnóstico por imagem , Tumor de Klatskin/cirurgia , Tumor de Klatskin/patologia , Endossonografia/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND AIMS: Fully covered metal stents (FCSEMSs) are increasingly used for treatment of biliary anastomotic strictures (ASs) after liver transplantation (LT), requiring fewer endoscopic interventions than does treatment with multiple plastic stents (MPSs). Previous studies, however, have reported adverse events such as stent migration and pancreatitis. The intraductal FCSEMS (ID-FCSEMS) potentially avoids these disadvantages. This study aimed to assess the efficacy and safety of ID-FCSEMSs compared with MPSs for AS. METHODS: The cohorts of LT patients treated for AS with endoscopic stenting between 2010 and 2019 from 2 Dutch liver transplantation centers were retrospectively analyzed. Patients treated with ID-FCSEMSs or MPSs were included. RESULTS: 80 patients (44 with ID-FCSEMSs vs 36 with MPSs) were included, with a median follow-up time of 52 versus 64 months (P = .183). Stricture resolution was 93% in the ID-FCSEMS versus 97% in the MPS group (P = 1.000) after a median of 19 and 26 weeks, respectively (P = .031). The median number of ERCPs was 2 in the ID-FCSEMS group versus 4 in the MPS group (P < .001). Stricture recurrence occurred in 33% of ID-FCSEMS versus 29% of MPS patients (P = .653) after a median of 24 and 55 weeks (P = .403). Stent migration occurred in 16% of ID-FCSEMS versus 39% of MPS patients (P = .020). Post-ERCP fever was observed in 34% of ID-FCSEMS patients compared with 14% of MPS patients (P = .038). No significant differences were found in pancreatitis rate between the groups, being 6.8% for ID-FCSEMSs and 5.6% for MPSs (P = .816). CONCLUSION: ID-FCSEMSs for the treatment of AS after LT provides similar stricture resolution and recurrence rates as MPSs, though with a significant reduction of procedures needed.
Assuntos
Colestase , Transplante de Fígado , Pancreatite , Stents Metálicos Autoexpansíveis , Humanos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Resultado do Tratamento , Stents/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatite/etiologia , Plásticos , Colestase/etiologia , Colestase/cirurgiaRESUMO
BACKGROUND AND AIMS: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury. The aim of this investigator-initiated FITCH trial (Fibrates for cholestatic ITCH) was to assess effects of bezafibrate on pruritus in patients with PSC, PBC, and SSC. METHODS: Patients with moderate to severe pruritus (≥5 of 10 on visual analog scale [VAS]) due to PSC, PBC, or SSC were recruited for this double-blind, randomized, placebo-controlled trial between 2016 and 2019. Patients received once-daily bezafibrate (400 mg) or placebo for 21 days. The primary end point was ≥50% reduction of pruritus (VAS; intention-to-treat). RESULTS: Of 74 randomized patients, 70 completed the trial (95%; 44 PSC, 24 PBC, 2 SSC). For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to ≥50% reduction of severe or moderate pruritus (P = .003). For secondary end points, bezafibrate reduced morning (P = .01 vs placebo) and evening (P = .007) intensity of pruritus (VAS) and improved the validated 5D-Itch questionnaire (P = .002 vs placebo). Bezafibrate also reduced serum alkaline phosphatase (-35%, P = .03 vs placebo) correlating with improved pruritus (VAS, P = .01) suggesting reduced biliary damage. Serum bile acids and autotaxin activity remained unchanged. Serum creatinine levels tended to mildly increase (3% bezafibrate, 5% placebo, P = .14). CONCLUSIONS: Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. TRIAL REGISTRATION: Netherlands Trial Register, ID: NTR5436 (August 3, 2015), ClinicalTrials.gov ID: NCT02701166 (March 2, 2016).
Assuntos
Bezafibrato/administração & dosagem , Colangite Esclerosante/complicações , Cirrose Hepática Biliar/complicações , Prurido/tratamento farmacológico , Adulto , Bezafibrato/efeitos adversos , Colangite Esclerosante/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Cirrose Hepática Biliar/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Prurido/diagnóstico , Prurido/etiologia , Prurido/psicologia , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Escala Visual AnalógicaRESUMO
Liver transplantation for primary sclerosing cholangitis (PSC) can be complicated by recurrence of PSC (rPSC). This may compromise graft survival but the effect on patient survival is less clear. We investigated the effect of post-transplant rPSC on graft and patient survival in a large European cohort. Registry data from the European Liver Transplant Registry regarding all first transplants for PSC between 1980 and 2015 were supplemented with detailed data on rPSC from 48 out of 138 contributing transplant centres, involving 1,549 patients. Bayesian proportional hazards models were used to investigate the impact of rPSC and other covariates on patient and graft survival. Recurrence of PSC was diagnosed in 259 patients (16.7%) after a median follow-up of 5.0 years (quantile 2.5%-97.5%: 0.4-18.5), with a significant negative impact on both graft (HR 6.7; 95% CI 4.9-9.1) and patient survival (HR 2.3; 95% CI 1.5-3.3). Patients with rPSC underwent significantly more re-transplants than those without rPSC (OR 3.6, 95% CI 2.7-4.8). PSC recurrence has a negative impact on both graft and patient survival, independent of transplant-related covariates. Recurrence of PSC leads to higher number of re-transplantations and a 33% decrease in 10-year graft survival.
Assuntos
Colangite Esclerosante , Transplante de Fígado , Teorema de Bayes , Colangite Esclerosante/cirurgia , Humanos , Transplante de Fígado/efeitos adversos , Recidiva , Sistema de Registros , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Single-operator peroral cholangioscopy (sPOCS) is considered a valuable diagnostic modality for indeterminate biliary strictures. Nevertheless, studies show large variation in its characteristics and measures of diagnostic accuracy. Our aim was to estimate the diagnostic accuracy of sPOCS visual assessment and targeted biopsies for indeterminate biliary strictures. Additional aims were: estimation of the clinical impact of sPOCS and comparison of diagnostic accuracy with brush cytology. METHODS: A retrospective single-center study of adult patients who underwent sPOCS for indeterminate biliary strictures was performed. Diagnostic accuracy was defined as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The clinical impact of sPOCS was assessed by review of medical records, and classified according to its influence on patient management. RESULTS: 80 patients were included, with 40â% having primary sclerosing cholangitis (PSC). Prior ERCP was performed in 88â%, with removal of a biliary stent prior to sPOCS in 55â%. The sensitivity, specificity, PPV, and NPV for sPOCS visual impression and targeted biopsies were 64â%, 62â%, 41â%, and 84â%, and 15â%, 65â%, 75â%, and 69â%, respectively. The clinical impact of sPOCS was limited; outcome changed management in 17â% of patients. Sequential brush cytology sensitivity, specificity, PPV, and NPV were 47â%, 95â%, 80â%, and 83â%. CONCLUSIONS: The diagnostic accuracy of sPOCS for indeterminate biliary strictures was found to be inferior to brush cytology, with a low impact on patient management. These findings are obtained from a select patient population with a high prevalence of PSC and plastic stents in situ prior to sPOCS.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Adulto , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos , Colangiopancreatografia Retrógrada Endoscópica , Constrição Patológica/etiologia , Endoscopia do Sistema Digestório , Humanos , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Intestinal transplantation is the standard treatment for patients with intestinal failure with severe complications due to parenteral nutrition; however, rejection leads to graft failure in approximately half of both adult and pediatric recipients within 5 years of transplantation. Although intensive immunosuppressive therapy is used in an attempt to reduce this risk, commonly used treatment strategies are generally practice- and/or expert-based, as head-to-head comparisons are lacking. In this ever-developing field, biologicals designed to prevent or treat rejection are used increasingly, with both infliximab and vedolizumab showing potential in the treatment of acute cellular rejection in individual cases and in relatively small patient cohorts. To help advance progress in clinical care, we review the current use of biologicals in intestinal transplantation, and we provide future perspectives to guide this progress.
Assuntos
Rejeição de Enxerto , Intestinos , Humanos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Intestinos/transplante , Intestinos/imunologia , Produtos Biológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Transplante de Órgãos/efeitos adversos , Animais , Infliximab/uso terapêuticoRESUMO
BACKGROUND: High-output intestinal fistulas and small bowel enterostomies are associated with morbidity and mortality. Current standard treatment for output reduction consists of fluid and dietary restrictions and medical therapy. There is conflicting evidence regarding the use of somatostatin analogues for output reduction. AIM: The aim of this study is to investigate whether lanreotide, added to current standard treatment, further reduces intestinal output in patients with high-output fistulas and enterostomies. METHODS: This was an open-label, multicentre, randomised controlled trial. Adult patients with a high-output intestinal fistula (>500 mL/24 h) or small bowel enterostomy (>1500 mL/24 h) more than 4 weeks post-surgery and receiving standard medical treatment (dietary- and fluid restriction, PPI, loperamide and codeine) for at least 2 weeks were eligible for inclusion. We randomised patients 1:1 between continuing standard treatment (control), and subcutaneous lanreotide 120 mg every 4 weeks with standard treatment. The primary outcome was the number of responders, with response defined as an output reduction of ≥25%, 8 weeks after randomisation. We also investigated the proportional change in output. RESULTS: We randomised 40 patients; 17 had a fistula and 23 a small bowel enterostomy. There were 9/20 responders in the intervention group and 2/20 in the control group (p = 0.013). The proportional output reduction was -26% (IQR -4 to -38) in the intervention group, compared to an increase of 4% (IQR 20 to -13) in the control group (p = 0.004). CONCLUSIONS: In patients with a high-output fistula or small bowel enterostomy, addition of lanreotide to current standard treatment can provide a clinically relevant output reduction. TRIAL REGISTRATION: EudraCT: 2013-003998-10.
Assuntos
Enterostomia , Fístula Intestinal , Intestino Delgado , Peptídeos Cíclicos , Somatostatina , Humanos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Peptídeos Cíclicos/uso terapêutico , Peptídeos Cíclicos/administração & dosagem , Enterostomia/métodos , Resultado do Tratamento , Intestino Delgado/cirurgia , Adulto , Fístula Intestinal/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêuticoRESUMO
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, but are associated with serious adverse events like pancreatitis. Current guidelines are limited to the first step in treating acute ICI-related pancreatitis with steroids but lack treatment advices for steroid dependent pancreatitis. We describe a case series of 3 patients who developed ICI-related pancreatitis with chronic features such as exocrine insufficiency and pancreatic atrophy at imaging. Our first case developed after treatment with pembrolizumab. The pancreatitis responded well after discontinuation of immunotherapy but imaging showed pancreatic atrophy and exocrine pancreatic insufficiency persisted. Cases 2 and 3 developed after treatment with nivolumab. In both, pancreatitis responded well to steroids. However during steroid tapering, pancreatitis recurred and the latter developed exocrine pancreatic insufficiency and pancreatic atrophy at imaging. Our cases demonstrate resemblances with autoimmune pancreatitis based on clinical and imaging findings. In line, both diseases are T-cell mediated and for autoimmune pancreatitis azathioprine is considered as maintenance therapy. Guidelines of other T-cell mediated diseases like ICI-related hepatitis suggest tacrolimus. After adding tacrolimus in case 2 and azathioprine in case 3, steroids could be completely tapered and no new episodes of pancreatitis have occurred. These findings support the idea that the treatment modalities for other T-cell mediated diseases are worthwhile options for steroid dependent ICI-related pancreatitis.
Assuntos
Pancreatite Autoimune , Insuficiência Pancreática Exócrina , Pancreatite , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Azatioprina/uso terapêutico , Tacrolimo/uso terapêutico , Pancreatite Autoimune/tratamento farmacológico , Prova Pericial , Pancreatite/diagnóstico , Pancreatite/etiologia , Insuficiência Pancreática Exócrina/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
Background & Aims: Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries. Methods: In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29-10.11) years post-LT. Results: In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5-5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08-2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC. Conclusions: An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC. Impact and implications: Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.
RESUMO
OBJECTIVES: Smoking behavior and genetic variations are important factors for the development of Crohn's disease (CD), but studies investigating the interaction between smoking and genetic background are scarce. We studied allelic associations of 19 confirmed variants located in 14 CD-associated genes or loci, in CD patients stratified for active smoking at diagnosis and passive smoking in childhood. METHODS: Genotyping data of 19 CD-associated single-nucleotide polymorphisms (SNPs) were available for 310 CD patients and 976 controls. Data on active smoking at diagnosis and passive smoking in childhood were obtained through a written questionnaire and a review of medical charts. RESULTS: The loci associated in smoking, but not in non-smoking, CD patients were 5p13.1 (rs17234657), DLG5 (rs2165047), NKX2-3 (rs10883365), and NOD2 (R702W). The loci associated in non-smoking, but not in smoking, CD patients were IL23R (rs7517847), 5p13.1 (rs9292777), IRGM (rs13361189 and rs4958847), IL12B (rs6887695), and CCNY (rs3936503). PTPN2 (rs2542151) was only associated in the smoking CD cohort (P=0.041), and not in the entire cohort (P=0.23) or in the non-smoking CD cohort (P=0.80). In passively smoking CD patients, associations with 13 SNPs in 9 loci were found, including PTPN2. In non-passive smoking CD patients, only associations with NOD2 (1007fsinsC and G908R) were found. CONCLUSIONS: The difference in associated genes between smoking and non-smoking CD patients implies a complex gene-environment interaction. Therefore, genetic studies of CD should be stratified for smoking behavior, as otherwise moderately associated genes such as PTPN2 can be missed.
Assuntos
Doença de Crohn/genética , Predisposição Genética para Doença/epidemiologia , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Fumar/genética , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Alelos , Estudos de Coortes , Intervalos de Confiança , Doença de Crohn/epidemiologia , Feminino , Seguimentos , Estudo de Associação Genômica Ampla , Humanos , Incidência , Subunidade p40 da Interleucina-12/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Probabilidade , Valores de Referência , Medição de Risco , Fatores Sexuais , Fumar/epidemiologia , Estatísticas não Paramétricas , Proteínas Supressoras de Tumor/genética , Adulto JovemRESUMO
Long-term morbidity and survival after orthotopic liver transplantation (OLT) are to a large degree determined by cardiovascular disease and cancer. Tobacco use is a well-known risk factor for both. The aim of this study was to examine smoking behavior before and after OLT and to define groups at risk for resuming tobacco use after OLT. In addition, we looked for a relation between smoking and morbidity after OLT. All 401 adult patients with a follow-up of at least 2 years after OLT were included. Data were collected from the charts. A questionnaire about smoking habits at 4 time points before and after OLT was sent to all 326 patients alive, and 301 (92%) patients responded. Both before and after OLT, 53% of patients never used tobacco, and around 17% were active smokers. Of the active smokers during the evaluation for OLT, almost one-third succeeded in cessation, often during the waiting time for OLT. Twelve percent of former smokers restarted smoking, mainly after OLT. Tobacco use was the highest in patients with alcoholic liver disease (52% were active smokers before OLT, and 44% were after OLT) and the lowest in patients with primary sclerosing cholangitis (1.4% were active smokers before OLT). At 10 years, the cumulative rate of malignancies was 12.7% in active smokers versus 2.1% in nonsmokers (P = 0.019). No effect on skin cancer or cardiovascular disease was found. In conclusion, smoking is a serious problem after OLT and increases the risk for malignancy. Prevention programs should focus not only on active smokers but also on former smokers.
Assuntos
Transplante de Fígado , Abandono do Hábito de Fumar , Fumar , Adolescente , Adulto , Idoso , Colangite Esclerosante/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Inquéritos Epidemiológicos , Hepatite C/cirurgia , Humanos , Cirrose Hepática Biliar/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Análise de Sobrevida , Adulto JovemRESUMO
INTRODUCTION: Extended criteria donor (ECD) livers are increasingly accepted for transplantation in an attempt to reduce the gap between the number of patients on the waiting list and the available number of donor livers. ECD livers; however, carry an increased risk of developing primary non-function (PNF), early allograft dysfunction (EAD) or post-transplant cholangiopathy. Ischaemia-reperfusion injury (IRI) plays an important role in the development of these complications. Machine perfusion reduces IRI and allows for reconditioning and subsequent evaluation of liver grafts. Single or dual hypothermic oxygenated machine perfusion (DHOPE) (4°C-12°C) decreases IRI by resuscitation of mitochondria. Controlled oxygenated rewarming (COR) may further reduce IRI by preventing sudden temperature shifts. Subsequent normothermic machine perfusion (NMP) (37°C) allows for ex situ viability assessment to facilitate the selection of ECD livers with a low risk of PNF, EAD or post-transplant cholangiopathy. METHODS AND ANALYSIS: This prospective, single-arm study is designed to resuscitate and evaluate initially nationwide declined ECD livers. End-ischaemic DHOPE will be performed for the initial mitochondrial and graft resuscitation, followed by COR of the donor liver to a normothermic temperature. Subsequently, NMP will be continued to assess viability of the liver. Transplantation into eligible recipients will proceed if all predetermined viability criteria are met within the first 150 min of NMP. To facilitate machine perfusion at different temperatures, a perfusion solution containing a haemoglobin-based oxygen carrier will be used. With this protocol, we aim to transplant extra livers. The primary endpoint is graft survival at 3 months after transplantation. ETHICS AND DISSEMINATION: This protocol was approved by the medical ethical committee of Groningen, METc2016.281 in August 2016 and registered in the Dutch Trial registration number TRIAL REGISTRATION NUMBER: NTR5972, NCT02584283.
Assuntos
Transplante de Fígado/métodos , Soluções para Preservação de Órgãos , Preservação de Órgãos/métodos , Sobrevivência de Tecidos , Substitutos Sanguíneos , Sobrevivência de Enxerto , Hemoglobinas , Artéria Hepática , Humanos , Hipotermia Induzida , Bombas de Infusão , Veia Porta , Estudos Prospectivos , Ressuscitação , Reaquecimento , Coleta de Tecidos e ÓrgãosRESUMO
BACKGROUND: Combination therapy of thiopurines and anti-tumor necrosis factor alpha (TNF-α) antibodies is the most effective medical treatment of Crohn's disease (CD). Data on thiopurines and anti-TNF-α antibodies in preventing surgical recurrence (need for re-resection) of CD are scarce. Therefore, we analyzed which factors were involved in surgical recurrence of CD in a large cohort of patients with CD operated in a regional and a university hospital. METHODS: This is a retrospective cohort study of 567 patients who underwent surgery for CD. Clinical data and risk factors for surgical recurrence were analyzed, focusing on medical therapy and hospital type. RESULTS: Overall, 237 (41.8%) patients developed a surgical recurrence, after a median of 70 (2-482) months. Before surgical recurrence, 235 patients (41.4%) and 116 patients (20.5%) used thiopurines and anti-TNF-α antibodies, respectively. Multivariate analysis identified 3 independent risk factors associated with surgical recurrence of CD. A higher risk was seen in patients with colonic disease compared with patients with ileal disease (hazard ratio, 1.56; 95% confidence interval, 1.10-2.21; P = 0.012) and in patients using multiple types of medication (hazard ratio, 1.38; 95% confidence interval, 1.25-1.54; P < 0.001). However, a lower risk was seen in patients using thiopurines (hazard ratio, 0.51; 95% confidence interval, 0.34-0.77; P = 0.001). CONCLUSIONS: Thiopurines are effective in preventing surgical recurrence of CD. The role of anti-TNF-α antibodies seems promising as well. Combination therapy of thiopurines and anti-TNF-α antibodies for prevention of surgical recurrence of CD should be studied in a randomized trial.
Assuntos
Azatioprina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Mercaptopurina/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Prevenção Secundária , Centros Médicos Acadêmicos , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Doença de Crohn/mortalidade , Doença de Crohn/cirurgia , Estudos Transversais , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
OBJECTIVE: Smoking is detrimental for Crohn's disease (CD), but beneficial for ulcerative colitis (UC). Earlier, we studied the effects of active and passive smoking in CD and UC patients from a university hospital. This study was conducted to assess the same effects in patients from a regional hospital. METHODS: A questionnaire focusing on cigarette smoke exposure was sent to 382 patients. Returned questionnaires (84%: 128 CD and 192 UC patients) were incorporated into a retrospective chart review about disease behaviour and received therapy. RESULTS: At diagnosis there were 52% (95% confidence interval: 43-60%) smokers among CD patients, 40% in a control population and 25% (95% confidence interval: 18-31%) among UC patients. There were less former (19 vs. 31%, P = 0.013) and never smokers at diagnosis (30 vs. 44%, P = 0.009) in CD than in UC. No detrimental effects of active or passive smoking on the course of CD were observed. UC patients who continued smoking after diagnosis needed less often two or more hospitalizations than never smokers (5 vs. 25%, P = 0.036). Otherwise no clear beneficial effects of active smoking on UC were observed. Passively smoking UC patients experienced more often extraintestinal manifestations (25 vs. 7%, P = 0.029) than nonpassive smokers. CONCLUSION: Also in a regional hospital inflammatory bowel disease population smoking is a risk factor to develop CD and protects against developing UC. We found no detrimental effects of smoking on the disease course of CD and no clear beneficial effects on the course of UC.
Assuntos
Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Hospitais Universitários , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Smoking is a remarkable risk factor in inflammatory bowel disease (IBD), with negative effects on Crohn's disease (CD) and positive effects on ulcerative colitis (UC). This makes different changes in smoking behaviour after diagnosis between CD and UC likely. Changes in active smoking, cessation plans and passive smoking were studied in IBD patients. METHODS: 820 IBD patients were sent a questionnaire on active and passive smoking, and cessation plans. A total of 675 (82%) patients (380 CD and 295 UC) responded. RESULTS: More ever smoking UC patients stopped smoking before diagnosis than CD patients (63% vs 22%; p<0.001), resulting in 30% former smokers at diagnosis in UC and 13% in CD (p<0.001). The smoking cessation rates at and after diagnosis are equal between CD and UC. Half of the CD patients stopped smoking after diagnosis leading to less present smokers in CD than in a control population (26% (95% confidence interval: 21.1%-29.9%) vs 33%). For both CD (22% vs 35%; p=0.044) and UC (24% vs 53%; p=0.024) continuing smokers after diagnosis were less often higher educated than quitters. Cessation plans (89%), passive smoking in childhood and present passive smoking were not different between CD and UC patients. CONCLUSION: There are no differences in changes in smoking behaviour at and after diagnosis between CD and UC patients, suggesting a lack of knowledge in these patients about the link between their disease and smoking behaviour. However, CD patients seem less refractory to smoking cessation than the general population. Therefore it is worthwhile putting energy in helping CD patients stop smoking.
Assuntos
Colite Ulcerativa/epidemiologia , Colite Ulcerativa/psicologia , Doença de Crohn/epidemiologia , Doença de Crohn/psicologia , Abandono do Hábito de Fumar/psicologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Comportamento de Escolha , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Feminino , Hospitais Universitários , Humanos , Masculino , Países Baixos , Educação de Pacientes como Assunto , Fatores de Risco , Autorrelato , Fumar/psicologia , Adulto JovemRESUMO
BACKGROUND: Smoking is a remarkable risk factor for inflammatory bowel disease (IBD), aggravating Crohn's disease (CD) while having beneficial effects on ulcerative colitis (UC). We studied the effects of active and passive smoking in Dutch IBD patients. METHODS: A questionnaire focusing on cigarette smoke exposure was sent to 820 IBD patients. Returned questionnaires were incorporated into a retrospective chart review, containing details about disease behavior and received therapy. RESULTS: In all, 675 IBD patients (380 [56%] CD and 295 [44%] UC) responded. At diagnosis there were 52% smokers in CD, 41% in the general population, and 28% in UC. The number of present smokers in CD is lower than in the general population (26% versus 35%). No detrimental effects of active smoking on CD were observed, but passive smokers needed immunosuppressants and infliximab more frequently than nonpassive smokers. Active smoking had beneficial effects on UC, indicated by reduced rates of colectomy, primary sclerosing cholangitis, and backwash-ileitis in active smokers compared to never smokers, and higher daily cigarette dose correlated with less extensive colitis and a lower need for therapy. Furthermore, smoking cessation after diagnosis was detrimental for UC patients, indicated by increased needs for steroids and hospitalizations for patients that stopped smoking after compared to before the diagnosis. CONCLUSIONS: Active smoking is a risk factor for CD, but does not affect the outcome; passive smoking is detrimental for the outcome of CD patients. In UC, active smoking shows dose-dependent beneficial effects. Our data suggest that passive smoking is a novel risk factor for CD.