RESUMO
INTRODUCTION: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities. METHODS: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups. RESULTS: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 µg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 µg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 µg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 µg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 µg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083). CONCLUSION: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose.
Assuntos
Doença de Crohn , Fármacos Gastrointestinais , Infliximab , Imageamento por Ressonância Magnética , Fístula Retal , Humanos , Doença de Crohn/sangue , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Estudos Transversais , Fístula Retal/sangue , Fístula Retal/etiologia , Fístula Retal/tratamento farmacológico , Infliximab/sangue , Infliximab/uso terapêutico , Infliximab/administração & dosagem , Masculino , Feminino , Adulto , Fármacos Gastrointestinais/sangue , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem , Pessoa de Meia-Idade , Adulto Jovem , Índice de Gravidade de Doença , Indução de RemissãoAssuntos
Prostatectomia , Fístula Retal , Retalhos Cirúrgicos , Doenças Uretrais , Fístula Urinária , Humanos , Masculino , Fístula Retal/cirurgia , Fístula Retal/etiologia , Fístula Urinária/etiologia , Fístula Urinária/cirurgia , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Doenças Uretrais/cirurgia , Doenças Uretrais/etiologia , Retalhos Cirúrgicos/transplanteRESUMO
BACKGROUND: Fistulizing perianal Crohn's disease poses a treatment challenge, and researchers postulate that this phenotype in young male patients could have a worst outcome. OBJECTIVE: Thus, the aim of this study was to assess whether sex influences the response to treatment for these patients. METHODS: This systematic review (PROSPERO CRD42022319629) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. We selected articles published in English, Spanish, Portuguese, and Italian between 2010 and 2020 in the PubMed and Science Direct databases. According to the PICO acronym, prospective studies in patients older than 18 years with the objective of treating fistulizing perianal Crohn's disease were selected. Studies in pediatric populations, retrospective, without treatment objectives, and that included only rectovaginal fistulas or a single sex were excluded. Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. RESULTS: Of the 1887 articles found, 33 were included. Most studies used anti-TNF drugs as treatment (n=11). Ten studies had subgroup analyses; of them, the two studies reporting sex differences used infliximab and adalimumab as treatment and showed that women had a longer fistula closure time than men. CONCLUSION: This systematic review showed that few data corroborate the difference between sexes in the treatment of fistulizing perianal Crohn's disease, possibly having a greater relationship with the phenotype. However, considering the lack of results, further studies with this objective and with standardization of fistulas and response assessment methods are needed.
Assuntos
Doença de Crohn , Fístula Retal , Criança , Humanos , Masculino , Feminino , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fístula Retal/etiologia , Fístula Retal/terapia , Resultado do Tratamento , Infliximab/uso terapêuticoRESUMO
Perianal fistula is a common complication of Crohn disease, and it is a great burden on the life and psychology of patients, but its treatment is still a difficult problem to face. In recent years, progress in the treatment of Crohn disease has progressed rapidly due to the advent of biological agents, but there has been a lack of research on perianal fistula in Crohn disease, and the direction of research has been scattered; therefore, the author reviews the traditional treatment of perianal fistula in Crohn disease in the context of the available literature and discusses emerging and potential therapeutic approaches. (AU)
Assuntos
Doença de Crohn/complicações , Fístula Retal/cirurgia , Fístula Retal/etiologia , Oxigênio/uso terapêutico , Terapia Biológica , Fístula Retal/tratamento farmacológico , Células-Tronco Mesenquimais , Imunossupressores/uso terapêuticoRESUMO
INTRODUCTION: Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry. MATERIALS AND METHODS: A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test. RESULTS: Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038). CONCLUSIONS: Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology.
Assuntos
Doença de Crohn , Fístula Retal , Humanos , Infliximab/uso terapêutico , Doença de Crohn/terapia , Doença de Crohn/tratamento farmacológico , Colômbia , Estudos Retrospectivos , Anticorpos Monoclonais/uso terapêutico , Resultado do Tratamento , Terapia Combinada , Fístula Retal/etiologia , Fístula Retal/terapia , Sistema de RegistrosRESUMO
One of the most challenging phenotypes of Crohn's disease is perianal fistulizing disease (PFCD). It occurs in up to 50% of the patients who also have symptoms in other parts of the gastrointestinal tract, and in 5% of the cases it occurs as the first manifestation. It is associated with severe symptoms, such as pain, fecal incontinence, and a significant reduction in quality of life. The presence of perianal disease in conjunction with Crohn's disease portends a significantly worse disease course. These patients require close monitoring to identify those at risk of worsening disease, suboptimal biological drug levels, and signs of developing neoplasm. The last 2 decades have seen significant advancements in the management of PFCD. More recently, newer biologics, cell-based therapies, and novel surgical techniques have been introduced in the hope of improved outcomes. However, in refractory cases, many patients face the decision of having a stoma made and/or a proctectomy performed. In this review, we describe modern surgical management and the most recent advances in the management of complex PFCD, which will likely impact clinical practice.
Assuntos
Doença de Crohn , Incontinência Fecal , Fístula Retal , Estomas Cirúrgicos , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Humanos , Qualidade de Vida , Fístula Retal/etiologia , Fístula Retal/cirurgiaRESUMO
BACKGROUND: Crohn's disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells. AIM: Systematic literature review to determine the different ways of adipose-derived mesenchymal stem cells administration in humans with luminal refractory and perianal fistulizing Crohn's disease. METHODS: It was conducted a search for articles (from 2008 to 2018) on PubMed and ScienceDirect databases using the keywords Crohn's disease, fistulizing Crohn's disease, luminal Crohn's disease and transplantation of mesenchymal stem cells or mesenchymal stem cells or stromal cells. Thirteen publications were selected for analysis. RESULTS: Only one study referred to the luminal Crohn´s disease. The number of cells administered was variable, occurring mainly through subcutaneous adipose tissue by liposuction. It could be highlighted the autologous transplant with exclusive infusion of mesenchymal stem cells. The procedures involved in pre-transplant were mainly curettage, setons placement and stitching with absorbable suture, and conducting tests and drug treatment for luminal Crohn´s disease. During transplant, the injection of mesenchymal stem cells across the fistula path during the transplant was mainly on the intestinal tract wall. CONCLUSION: Although the use of mesenchymal stem cells is promising, the transplant on the luminal region should be more investigated. The injection of mesenchymal stem cells, exclusively, is more explored when compared to treatment with other products. The preparation of the fistulizing tract and the location of cell transplantation involve standardized health care in most studies.