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1.
Dis Colon Rectum ; 64(4): 446-458, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33399407

RESUMEN

BACKGROUND: The Parks classification has been used for the classification of anal fistula for several years, but it does not allow for risk factors for failure after surgery. OBJECTIVE: This study aimed to describe a modification of the Parks classification of anal fistula and examine its predictive validity in the assessment of the outcome of anal fistula in terms of failure of healing and fecal incontinence. DESIGN: This is a retrospective review of a prospective database. SETTING: This study was conducted in the Colorectal Surgery Unit, Mansoura University Hospitals. PATIENTS: Adult patients with anal fistula who underwent surgery were included. INTERVENTIONS: Five risk factors for failure after fistula surgery were identified from the literature and were examined by multivariate analysis of our patients. Four risk factors proved to be significant independent predictors of failure: secondary extensions, horseshoe fistula, previous fistula surgery, and anterior anal fistula in women. We modified the Parks classification by dividing the transsphincteric type into high and low and by grouping supra- and extrasphincteric anal fistulas into 1 group. The first 3 stages were subdivided according to the absence or presence of predictors of failure. MAIN OUTCOME MEASURES: The primary outcome measured was the validity of the modified Parks classification with regard to the rates of failure and fecal incontinence after surgical treatment of each stage of anal fistula. RESULTS: A total of 665 patients with cryptoglandular anal fistula were included. Failure rates increased from 2.3% (95% CI, 0.9%-4.7%), to 17.4% (95% CI, 10.8%-25.9%), 19.5% (95% CI, 15%-24.6%), and 30.7% (95% CI, 9.1%-61.4%) across the 4 stages. The area under the receiver operating characteristic curve was 0.90 (95% CI, 0.85-0.94) indicating the strong discriminative ability of the final multivariable predictive model. The increase in failure and incontinence rates across the fistula stages was significant. LIMITATIONS: This is a retrospective, single-center study. CONCLUSION: Inclusion of predictors of poor outcome into the modified classification helped differentiate simple and complex fistulas within each stage and between the different stages, which can help in assessment and decision making for anal fistula. See Video Abstract at http://links.lww.com/DCR/B441. MODIFICACIN DE LA CLASIFICACIN DE PARKS DE LA FSTULA ANAL CRIPTOGLANDULAR: ANTECEDENTES:La clasificación de Parks se ha utilizado para la clasificación de la fístula anal durante varios años, sin embargo, no tuvo en cuenta los factores de riesgo de fracaso después de la cirugía.OBJETIVO:Describir una modificación de la clasificación de Parks de fístula anal y examinar su validez predictiva en la evaluación de los resultados de la fístula anal en términos de fracaso de la cicatrización e incontinencia fecal.DISEÑO:Revisión retrospectiva de la base de datos prospectiva.AJUSTE:Unidad de Cirugía Colorrectal, Hospital Universitario de Mansoura.PACIENTES:Pacientes adultos con fístula anal intervenidos quirúgicamente.INTERVENCIONES:Se identificaron cinco factores de riesgo de fracaso después de la cirugía de fístula de la literatura y se examinaron mediante análisis multivariante de nuestros pacientes. Cuatro factores de riesgo demostraron ser importantes predictores independientes de fracaso: extensiones secundarias, fístula en herradura, cirugía de fístula previa y fístula anal anterior en mujeres. Modificamos la clasificación de Parks dividiendo el tipo transesfinteriano en alto y bajo y agrupando la fístula anal supraesfinteriana y extraesfinteriana en un grupo. Las tres primeras etapas se subdividieron según la ausencia o presencia de predictores de fracaso.PRINCIPALES MEDIDAS DE RESULTADO:Validez de la clasificación de Parks modificada con respecto a las tasas de fracaso e incontinencia fecal después del tratamiento quirúrgico de cada etapa de la fístula anal.RESULTADOS:Se incluyeron 665 pacientes con fístula anal criptoglandular. Las tasas de fracaso aumentaron del 2,3% (IC del 95%: 0,9-4,7%), al 17,4% (IC del 95%: 10,8 al 25,9%), 19,5% (IC del 95%: 15-24,6%) y 30,7% (95% IC: 9,1- 61,4%) en las cuatro etapas. El área bajo la curva característica operativa del receptor fue 0,90 (IC del 95%: 0,85-0,94), lo que indica una fuerte capacidad discriminativa del modelo predictivo multivariable final. El aumento en las tasas de fracaso e incontinencia en las etapas de la fístula fue significativo.LIMITACIONES:Estudio retrospectivo, unicéntrico.CONCLUSIÓN:La inclusión de predictores de mal resultado en la clasificación modificada ayudó a diferenciar las fístulas simples y complejas dentro de cada etapa y entre las diferentes etapas, lo que puede ayudar en la evaluación y toma de decisiones para la fístula anal. Consulte Video Resumen en http://links.lww.com/DCR/B441.


Asunto(s)
Incontinencia Fecal/epidemiología , Glándulas Perianales/patología , Fístula Rectal/clasificación , Fístula Rectal/cirugía , Adulto , Animales , Manejo de Datos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento
3.
Aliment Pharmacol Ther ; 51(7): 719-727, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32080886

RESUMEN

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedades del Ano/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Adulto , Animales , Estudios de Cohortes , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Glándulas Perianales/patología , Fístula Rectal/tratamiento farmacológico , Recurrencia , Resultado del Tratamiento , Adulto Joven
4.
Front Immunol ; 10: 1244, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31258526

RESUMEN

Adipose mesenchymal stem cells (ASC) are considered minimally immunogenic. This is due to the low expression of human leukocyte antigens I (HLA-I), lack of HLA-II expression and low expression of co-stimulatory molecules such as CD40 and CD80. The low rate of observed immunological rejection as well as the immunomodulatory qualities, position ASC as a promising cell-based therapy for the treatment of a variety of inflammatory indications. Yet, few studies have addressed relevant aspects of immunogenicity such as ASC donor-to-patient HLA histocompatibility or assessment of immune response triggered by ASC administration, particularly in the cases of presensitization. The present study aims to assess allo-immune responses in a cohort of Crohn's disease patients administered with allogeneic ASC (darvadstrocel formerly Cx601) for the treatment of complex perianal fistulas. We identified donor-specific antibodies (DSA) generation in a proportion of patients and observed that patients showing preexisting immunity were prone to generating DSA after allogeneic therapy. Noteworthy, naïve patients generating DSA at week 12 (W12) showed a significant reduction in DSA titer at week 52 (W52), whereas DSA titer was reduced in pre-sensitized patients only with no specificities against the donor administered. Remarkably, we did not observe any correlation of DSA generation with ASC therapeutic efficacy. In vitro complement-dependent cytotoxicity (CDC) studies have revealed limited cytotoxic levels based upon HLA-I expression and binding capacity even in pro-inflammatory conditions. We sought to identify CDC coping mechanisms contributing to the limited cytotoxic killing observed in ASC in vitro. We found that ASC express membrane-bound complement regulatory proteins (mCRPs) CD55, CD46, and CD59 at basal levels, with CD46 more actively expressed in pro-inflammatory conditions. We demonstrated that CD46 is a main driver of CDC signaling; its depletion significantly enhances sensitivity of ASC to CDC. In summary, despite relatively high clearance, DSA generation may represent a major challenge for allogeneic cell therapy management. Sensitization may be a significant concern when evaluating re-treatment or multi-donor trials. It is still unknown whether DSA generation could potentially be the consequence of donor-to-patient interaction and, therefore, subsequently link to efficacy or biological activity. Lastly, we propose that CDC modulators such as CD46 could be used to ultimately link CDC specificity with allogeneic cell therapy efficacy.


Asunto(s)
Enfermedad de Crohn/terapia , Fístula/terapia , Rechazo de Injerto/inmunología , Trasplante de Células Madre Mesenquimatosas , Glándulas Perianales/patología , Complicaciones Posoperatorias/inmunología , Tejido Adiposo/citología , Adulto , Animales , Células Cultivadas , Estudios de Cohortes , Activación de Complemento , Enfermedad de Crohn/complicaciones , Femenino , Fístula/complicaciones , Rechazo de Injerto/etiología , Antígenos HLA/inmunología , Humanos , Inmunidad Humoral , Inmunización , Isoantígenos/inmunología , Masculino , Proteína Cofactora de Membrana/metabolismo , Células Madre Mesenquimatosas/citología , Glándulas Perianales/cirugía , Trasplante Homólogo
7.
Inflamm Bowel Dis ; 25(7): 1227-1236, 2019 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-30576474

RESUMEN

BACKGROUND: Perianal complications in patients with Crohn's disease are common and have a negative impact on the patients' quality of life. Data about the long-term disease course of perianal Crohn's disease in the era of biological treatment are limited. In this population-based cohort study, we sought to investigate the occurrence, clinical risk factors, and disease course of perianal disease. METHODS: A total of 213 Crohn's disease patients were included in a prospective population-based inception cohort. Data were retrieved from medical records and national health administrative databases. Perianal disease was defined as a perianal fistula and/or abscess. Associations between outcomes and covariates were analyzed by Cox regression analysis. RESULTS: A total of 48 (22.5%) patients developed perianal disease after 10 years. Colonic disease location (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.01-3.92) and penetrating behavior (HR, 5.65; 95% CI, 2.65-12.03) were associated with the development of perianal disease. The cumulative risk of undergoing abdominal surgery was 51% after 10 years. Patients with perianal disease had a higher rate of resection (HR, 3.92; 95% CI, 1.86-8.67) and hospitalization (HR, 1.01; 95% CI, 1.00-1.01). There was no significant difference in the rate of sick leave, unemployment, or disability pension between patients with and without perianal disease. CONCLUSIONS: Patients with perianal disease carry a higher risk of surgery and hospitalization, and this suggests a more severe disease course and poorer prognosis among these patients, even in the era of biological treatment. These findings underline the importance of optimizing treatment strategies for patients with perianal disease.


Asunto(s)
Enfermedades del Ano/epidemiología , Enfermedad de Crohn/epidemiología , Glándulas Perianales/patología , Adolescente , Adulto , Animales , Enfermedades del Ano/patología , Enfermedades del Ano/terapia , Enfermedad de Crohn/patología , Enfermedad de Crohn/terapia , Dinamarca/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Adulto Joven
9.
Vet Clin North Am Small Anim Pract ; 49(1): 53-65, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30213533

RESUMEN

Canine perianal fistulas are painful sinus tracts and ulcers that spontaneously develop in the skin around the anus. Middle-aged German shepherd dogs are most commonly affected and may have a genetic susceptibility. Although the disease was once believed related to conformational factors and primarily managed surgically, an immune-mediated pathogenesis is now recognized. Long-term medical management with immunomodulatory agents has become standard of care for canine perianal fistulas. Perianal fistulas can be debilitating and have a negative impact on quality of life of dogs and owners. Accurate diagnosis and aggressive medical therapy are key to successful management of canine perianal fistulas.


Asunto(s)
Enfermedades del Ano/veterinaria , Enfermedades de los Perros/diagnóstico , Fístula/veterinaria , Glándulas Perianales/patología , Animales , Enfermedades del Ano/diagnóstico , Perros , Fístula/diagnóstico , Medicina Veterinaria/tendencias
10.
Vet Clin Pathol ; 47(4): 634-637, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30415503

RESUMEN

BACKGROUND: Perianal (hepatoid) gland tumors are common in dogs, and the distinction between the benign and malignant forms is clinically important. Cytology of these tumors typically contains many large hepatoid cells and fewer small basal cells. OBJECTIVES: The objective of this study was to determine whether the proportion of the smaller basaloid reserve cells in cytologic samples from perianal tumors correlates with malignancy. METHODS: Eighty-three cases of cytologically diagnosed perianal gland tumors with corresponding histopathologic sections were identified from two separate institutions and included six (7.2%) malignant tumors and 77 (92.8%) benign tumors. The proportion of basal cells from each sample was evaluated. RESULTS: No difference between these groups was found, although the study was sufficiently powered to detect an approximately 1.5-fold change in basal cell proportion. CONCLUSIONS: This report found no evidence that the proportion of basal cells in canine perianal tumor cytology is an indication of the potential for malignancy. We, therefore, do not recommend citing this feature in cytologic reports or when communicating with clinicians.


Asunto(s)
Neoplasias de las Glándulas Anales/patología , Enfermedades de los Perros/patología , Neoplasias de las Glándulas Anales/diagnóstico , Animales , Estudios de Casos y Controles , Enfermedades de los Perros/diagnóstico , Perros , Femenino , Masculino , Glándulas Perianales/citología , Glándulas Perianales/patología , Estudios Retrospectivos
11.
Gastroenterol. hepatol. (Ed. impr.) ; 41(9): 576-582, nov. 2018. tab
Artículo en Español | IBECS | ID: ibc-178125

RESUMEN

Los agentes anti-factor de necrosis tumoral (anti-TNF) son fármacos de uso común en los pacientes con enfermedad inflamatoria crónica intestinal (EICI) y han demostrado ser efectivos en inducción y mantenimiento en enfermedad de Crohn y colitis ulcerosa, así como en pacientes con afectación fistulizante perianal. Sin embargo, la evidencia relativa al uso de estos fármacos en otros escenarios dentro de EICI es menos sólida. Es el caso de la enfermedad de Crohn con afectación estenosante, penetrante o perianal no fistulizante, de las manifestaciones extraintestinales de la EICI y de las complicaciones del reservorio ileoanal. El objetivo de esta revisión fue realizar un análisis de la literatura disponible y determinar el papel de los anti-TNF en la práctica clínica en pacientes afectos por estas complicaciones


Anti-tumor necrosis factor agents (anti-TNF) drugs are commonly used in patients with inflammatory bowel disease (IBD) and have proven effective in both induction and maintenance therapy in luminal Crohn's disease and ulcerative colitis. Their efficacy has also been proven in fistulising perianal Crohn's disease. However, the evidence in other scenarios, such as stricturing, penetrating and non-fistulising perianal Crohn's disease, extraintestinal IBD manifestations and ileoanal reservoir complications, is not as robust. The aim of this review was to perform an analysis of the available literature and to determine the role of anti-TNF drugs in common clinical practice in patients affected by these complications


Asunto(s)
Humanos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Enfermedad de Crohn/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedad Crónica , Constricción Patológica/fisiopatología , Estudios de Cohortes , Estudios Prospectivos , Fístula Rectal/tratamiento farmacológico , Glándulas Perianales/patología , Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico
13.
Vet Clin Pathol ; 47(4): 649-653, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30347120

RESUMEN

Fine-needle aspirates from a perianal mass on an 8-year-old, intact male, Miniature Poodle presenting for tenesmus showed a uniform population of well-differentiated hepatoid cells with no notable criteria of malignancy. The cytologic diagnosis was a perianal gland tumor, with adenoma likely given the cytomorphology. The abdominal ultrasound revealed multiple, markedly enlarged, intra-abdominal lymph nodes. LN aspirates also showed well-differentiated polygonal, hepatoid cells displaying no notable cellular atypia. The presence of the metastasis led to the interpretation of a well-differentiated, malignant perianal gland tumor despite the benign cellular appearance. Histopathology of the surgically excised perianal mass and one enlarged abdominal lymph node revealed lobules of uniform polygonal hepatoid cells arranged in organized islands and trabeculae surrounded by a single layer of uniform reserve cells. Few mitotic figures were present. The only histopathologic indication of malignancy within the primary mass was the presence of small islands of well-differentiated hepatoid cells infiltrating into adjacent tissue and possible lymphatic invasion. The histopathologic diagnosis was perianal gland adenocarcinoma. Most textbooks describe perianal gland adenocarcinomas as showing increased cellular atypia including pleomorphism, disorganization of hepatoid cells, and increased numbers of pleomorphic reserve cells with mitotic figures. This case is an example of the occurrence of a well-differentiated perianal gland tumor with metastasis and highlights the importance of realizing that with these tumors, a benign cytologic and histologic appearance may not correlate with biologic behavior. To the authors' knowledge, this is the first case reporting both the cytologic and histologic appearance of a well-differentiated metastatic hepatoid gland tumor.


Asunto(s)
Neoplasias de las Glándulas Anales/patología , Enfermedades de los Perros/patología , Neoplasias de las Glándulas Anales/diagnóstico , Animales , Biopsia con Aguja Fina/veterinaria , Enfermedades de los Perros/diagnóstico , Perros , Ganglios Linfáticos/patología , Masculino , Glándulas Perianales/patología
14.
Expert Opin Biol Ther ; 18(7): 737-745, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29939815

RESUMEN

INTRODUCTION: Crohn's disease (CD) is a chronic, recurring, idiopathic disease which is associated with imbalanced mucosal immune response, manifesting as a chronic inflammation of any location throughout the gastrointestinal tract. The purpose of currently available therapy is to suppress the heightened immune response. However, these treatments have no direct influence on the healing process of damaged tissues. The mesenchymal stem cell (MSC) therapy may represent a new alternative solution in both luminal and fistulizing CD, as it is able to inhibit the inflammation and promote the regeneration process at the same time. AREAS COVERED: Aim of this review is to summarize the existing clinical data about the clinical impact of MSC therapy in luminal and perianal fistulizing CD. EXPERT OPINION: Clinical trials demonstrated that MSC transplantation has an outstanding, durable efficacy with low fistula recurrence in biological therapy-refractory fistulizing CD; however, further clinical trials are required to confirm its effectiveness in luminal CD. Unlike to biological therapy, MSCs are able to promote the regeneration process of damaged tissues as well. This additional benefit besides their sustained immunosuppressive effect with no decrease of efficiency over time makes MSCs a new, highly potential therapeutic approach in the management of inflammatory bowel disease.


Asunto(s)
Enfermedad de Crohn/terapia , Trasplante de Células Madre Mesenquimatosas , Animales , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/patología , Humanos , Inflamación , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/terapia , Fístula Intestinal/epidemiología , Fístula Intestinal/etiología , Fístula Intestinal/patología , Fístula Intestinal/terapia , Trasplante de Células Madre Mesenquimatosas/estadística & datos numéricos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Glándulas Perianales/patología , Fístula Rectal/epidemiología , Fístula Rectal/etiología , Fístula Rectal/patología , Fístula Rectal/terapia , Cicatrización de Heridas
15.
Inflamm Bowel Dis ; 24(11): 2452-2460, 2018 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-29860270

RESUMEN

Background: The differentiation between intestinal tuberculosis (ITB) and Crohn's disease (CD) is a challenge. The aim of this study was to investigate a predictive model for differential diagnosis between ITB and CD. Methods: A total of 268 patients who were suspected of having ITB or CD were prospectively recruited between January 2013 and September 2016. The clinical, laboratory, radiological, endoscopic, and histological features were investigated and subjected to univariate and multivariate analyses. The final predictive model was developed based on the regression coefficients of multivariate logistic regression. To validate the model, the same regression equation was tested on the other group. Results: A total of 239 patients had a final diagnosis, including 86 ITB and 153 CD. Five variables (perianal disease, pulmonary involvement, longitudinal ulcer, left colon, and ratio of tuberculosis-specific antigen to phytohaemagglutinin) were selected for the predictive model to discriminate between ITB and CD. In the predictive model of the training data set, the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy, with a cutoff level of 0.29, were 0.975 (95% confidence interval [CI], 0.939-0.993), 96.7%, 90.7%, and 92.8%, respectively. Application of the predictive model to the validation data set showed similar performance in distinguishing ITB from CD. The area under the ROC curve, sensitivity, specificity, and accuracy were 0.950 (95% CI, 0.871-0.987), 88.5%, 93.5%, and 91.7%, respectively. Conclusions: This 5-marker predictive model could be conveniently used by clinicians to draw a reliable differential diagnosis between ITB and CD in clinical practice. 10.1093/ibd/izy154_video1izy154.video15790725497001.


Asunto(s)
Biomarcadores/análisis , Colon/patología , Enfermedad de Crohn/diagnóstico , Glándulas Perianales/patología , Fitohemaglutininas/análisis , Úlcera/patología , Adulto , Animales , Antígenos Bacterianos/análisis , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Tuberculosis Gastrointestinal/diagnóstico
16.
Aliment Pharmacol Ther ; 47(9): 1253-1260, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29520808

RESUMEN

BACKGROUND: Patient reported outcomes regarding perianal disease and faecal incontinence in the community-based inflammatory bowel disease population are poorly described. AIMS: To determine the impacts of perianal disease and faecal incontinence on quality of life and employment in inflammatory bowel disease patients. METHODS: For this cross-sectional study, a comprehensive survey was sent out to members of the Dutch National Crohn's and Colitis patient organisation. Validated questionnaires regarding faecal incontinence and active perianal disease were used to estimate its prevalence's. The effect on the quality of life (36-Item Short Form Survey) and on employment status (multivariate binary regression analysis) was assessed in this inflammatory bowel disease population. RESULTS: A total number of 1092 returned questionnaires (58% responders) were used for analysis; 750 respondents (69%) were female; mean age was 47 years (IQR 35-59). In 621 patients (57%) Crohn's disease, in 422 (39%) ulcerative colitis and in 49 (4%) patients unclassifiable inflammatory bowel disease was self-reported. The 114 patients (10%) with a stoma were excluded for continence related analyses. Faecal incontinence was reported in 555 patients (57%), was comparable between the different inflammatory bowel disease diagnoses and affected all 36-Item Short Form Survey subscales adversely (incontinence vs continence: Physical functioning 75 vs 84, P < 0.0001; Limitations due to physical health 49 vs 63, P < 0.0001; Limitations due to emotional problems 49 vs 64, P < 0.0001; Energy/fatigue 47 vs 53, P < 0.0001; Emotional well-being 71 vs 74, P = 0.005; Social functioning 63 vs 73, P < 0.0001; Pain 66 vs 75, P < 0.0001; General health 41 vs 48, P < 0.0001). Active perianal disease was reported in 39% Crohn's disease, 16% ulcerative colitis (84% fissures) and 20% unclassifiable inflammatory bowel disease patients. Faecal incontinence was more common in patients with perianal disease (67% vs 53%, P = 0.003). When correcting for age, disease duration, inflammatory bowel disease-related surgery and faecal incontinence, active perianal disease was independently affecting employment (OR 0.67; 95% CI 0.50-0.91; P = 0.01). CONCLUSIONS: Faecal incontinence and perianal disease are quality of life determining factors. Faecal incontinence needs more attention among clinicians, and development of new (drug) therapies needs to be focussed on perianal disease.


Asunto(s)
Enfermedades del Ano/epidemiología , Empleo/estadística & datos numéricos , Incontinencia Fecal/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Calidad de Vida , Adulto , Animales , Enfermedades del Ano/etiología , Enfermedades del Ano/psicología , Estudios Transversales , Incontinencia Fecal/etiología , Incontinencia Fecal/psicología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/psicología , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Glándulas Perianales/patología , Prevalencia , Encuestas y Cuestionarios
17.
Gastroenterol. hepatol. (Ed. impr.) ; 41(3): 205-221, mar. 2018. ilus, tab
Artículo en Español | IBECS | ID: ibc-171135

RESUMEN

Las tiopurinas (azatioprina y mercaptopurina) se usan frecuentemente en pacientes con enfermedad inflamatoria intestinal. En este documento, revisaremos sus principales indicaciones, así como aspectos prácticos de seguridad, eficacia y modo de empleo. Sus usos principales son el mantenimiento de la remisión en la enfermedad corticodependiente o tras el control de un brote grave de colitis ulcerosa con ciclosporina, la prevención de la recurrencia posquirúrgica en enfermedad de Crohn y el empleo en terapia combinada junto con biológicos. El 30-40% de pacientes no responderá al tratamiento y un 10-20% no tolerará el tratamiento por efectos adversos. Antes de iniciarlas, se recomienda evaluar el estado de inmunización frente a ciertas infecciones; la determinación previa de la actividad de la tiopurina·metiltransferasa (TPMT) no es imprescindible, pero permite mayor seguridad inicial. La dosis adecuada es de 2,5mg/kg/día para azatioprina y de 1,5mg/kg/día para mercaptopurina. Algunos efectos adversos son idiosincrásicos (intolerancia digestiva, pancreatitis, fiebre, artromialgias, exantema y algunos casos de hepatotoxicidad). Otros son dosis-dependientes (mielotoxicidad y otros tipos de hepatotoxicidad) y su vigilancia debe mantenerse mientras dure el tratamiento. Si son ineficaces o aparecen efectos adversos, puede recurrirse al cambio de tiopurina, la reducción de dosis, combinar dosis bajas de azatioprina con alopurinol y determinar metabolitos antes de descartar su uso. Los tumores de piel distintos al melanoma, los linfomas y los tumores del tracto urinario se han relacionado con su administración. Las tiopurinas son fármacos seguros en la concepción, gestación y lactancia (AU)


Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects. Before they are prescribed, immunisation status against certain infections should be checked. Determination of thiopurine methyltransferase activity (TPMT) is not mandatory but it increases initial safety. The appropriate dose is 2.5mg/kg/day for azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and other types of hepatotoxicity), and their surveillance should never be interrupted during treatment. If therapy fails or adverse effects develop, management can include switching from one thiopurine to the other, reducing the dose, combining low doses of azathioprine with allopurinol and assessing metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use is safe during conception, pregnancy and breastfeeding (AU)


Asunto(s)
Humanos , Masculino , Femenino , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Purinas/uso terapéutico , Enfermedad de Crohn/complicaciones , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Biomarcadores de Tumor/análisis , Glándulas Perianales , Glándulas Perianales/patología , Azatioprina/uso terapéutico
19.
In Vivo ; 31(4): 543-549, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28652418

RESUMEN

BACKGROUND/AIM: Hemorrhoidectomy is often associated with significant postoperative complications that may result in slow wound healing. The traditional Chinese medicine (TCM) compound Sophora flavescens (CSF) has shown efficacy on many inflammatory disorders. The aim of the present study was to examine the efficacy of CSF on wound healing in a rat model of perianal ulceration. MATERIALS AND METHODS: A rat model of perianal ulceration was induced by subcutaneous injection of 75% glacial acetic acid. The animals with induced perianal ulcer received topical treatment of low, medium, and high doses of CFS twice daily. Potassium permanganate (PP); 0.02%) was given to the animals for comparison. Macroscopic and histological assessments of the ulcerated area were performed after treatment. The expression of pro-inflammatory cytokines prostaglandin E2 (PGE2) and interleukin-8 (IL-8) was detected by immunohistochemical analysis. RESULTS: Topical administration of medium- and high-dose CSF significantly enhanced perianal ulcer healing as compared to the untreated control (p<0.05). The macroscopic ulceration score was significantly reduced only in the high-dose CSF-treated group as compared to the control (p<0.01). All doses of CSF and PP ameliorated histological damages in the rats with induced perianal ulceration. High-dose CSF or PP significantly reduced the expression of PGE2 and IL-8 as compared to the control (p<0.01). No treatment-related toxicity was found in either the CSF- or the PP-treated mice. CONCLUSION: CSF enhances wound healing in a rat model of perianal ulceration. The inhibitory effect of CSF on pro-inflammatory cytokines PGE2 and IL-8 may be involved in the mechanism of enhanced wound-healing.


Asunto(s)
Extractos Vegetales/farmacología , Sophora/química , Úlcera/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Humanos , Medicina Tradicional China , Glándulas Perianales/efectos de los fármacos , Glándulas Perianales/patología , Extractos Vegetales/química , Permanganato de Potasio/administración & dosificación , Ratas , Úlcera/patología
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