Search

Background Anal fistula treatment aims to eradicate the fistula, preserve the sphincter, prevent recurrence, and allow an early return to daily activities for the patient. Because of the difficulty of achieving these goals, stem cell-based therapy has emerged for the treatment of complex perianal fistula with promising results. Objective The objective of this study was to evaluate the safety of allogeneic mesenchymal stem cells in the treatment of complex anal fistula in patients without Crohn's disease. Design This was a prospective nonrandomized phase I clinical trial. Settings This study was conducted at a second-level hospital. Patients Twenty consecutive patients diagnosed with a complex fistula were included. Interventions All patients received 40 × 106 allogeneic mesenchymal stem cells. In patients with 2 tracts, 20 × 106 stem cells were applied on each tract. Main outcome measures The patients were discharged 24 hours after the procedure and were evaluated at 1, 2, 4, 8, 16, and 24 weeks after the application. The long-term follow-up was performed 1 year after the procedure. Results The procedure was performed in a total of 20 patients from October 1, 2016, to October 31, 2017; 1 patient was eliminated from the final data analysis. No adverse effects were reported within the first 24 hours, and all the patients were discharged asymptomatic. Three patients (15%) presented with perianal abscess. In 1 patient, the abscess appeared at the fourth week, and, in the other 2 patients, the abscess was diagnosed at week 8. Complete closure was achieved in 13 (69%) patients. Limitations This was a nonrandomized controlled trial. Conclusion The use of allogeneic mesenchymal stem cells as a treatment is a safe option for the management of complex perianal fistula not associated with Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B443. Seguridad de las clulas madre mesenquimales alognicas derivadas del tejido adiposo para el tratamiento de fstulas perianales complejas no asociadas con la enfermedad de crohn ensayo clnico de fase i ANTECEDENTES:El tratamiento de la fistula anal tiene como objetivo erradicar la fistula, preservar el esfinter, prevenir la recurrencia y permitir un retorno temprano a las actividades diarias del paciente. Debido a la dificultad de alcanzar estos objetivos, ha surgido una terapia basada en celulas madre para el tratamiento de la fistula perianal compleja con resultados prometedores.OBJETIVO:El objetivo de este estudio fue evaluar la seguridad de las celulas madre mesenquimales alogenicas en el tratamiento de la fistula anal compleja en pacientes sin enfermedad de Crohn.DISENO:Este fue un ensayo clinico prospectivo no aleatorizado de fase I.AMBIENTE:Este estudio se realizo en un hospital de segundo nivel.PACIENTES:Veinte pacientes consecutivos diagnosticados de fistula compleja.INTERVENCIONES:Todos los pacientes recibieron 40 x 106 celulas madre mesenquimales alogenicas, en pacientes con dos tractos, se aplicaron 20 x 106 celulas madre en cada tracto.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron dados de alta 24 horas despues del procedimiento y fueron evaluados 1, 2, 4, 8, 16, 24 semanas despues de la aplicacion. El seguimiento a largo plazo se realizo un ano despues del procedimiento.RESULTADOS:El procedimiento se realizo en un total de 20 pacientes desde el 1 de octubre de 2016 al 31 de octubre de 2017; un paciente fue eliminado del analisis de datos final. No se informaron efectos adversos en las primeras 24 horas, todos los pacientes fueron dados de alta asintomaticos. Tres pacientes (15%) presentaron absceso perianal. En un paciente, el absceso aparecio a la cuarta semana y en los otros dos pacientes el absceso se diagnostico en la octava semana. El cierre completo se logro en 13 (69%) de los pacientes.LIMITACIONES:Este fue un ensayo controlado no aleatorio.CONCLUSION:El uso de celulas madre mesenquimales alogenicas como tratamiento es una opcion segura para el manejo de la fistula perianal compleja no asociada con la enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B443.

Colorectal cancer (CRC) is the fourth leading worldwide cause of cancer-associated mortalities. Nuclear factor-κB (NF-κB) is a transcriptional regulator of multiple genes associated with CRC. Tumor tissue were compared with normal adjacent mucosa from 30 sporadic patients with CRC were investigated. A total of 8 non-CRC patients were analyzed as a control group. In the present study, the protein expression of NF-κB/p65 was detected by immunohistochemistry, and the gene expression profiles of cyclin D1 (CCND1), prostaglandin-endoperoxide synthase 2, vascular endothelial growth factor A, matrix metallopeptidase 9, BCL2 apoptosis regulator (BCL2), BCL2 like 1, nitric oxide synthase 2, tumor necrosis factor and arachidonate lipoxygenase were detected by reverse transcription-quantitative polymerase chain reaction. NF-κB/p65 and genes expression profiles were classified according to tumor-node-metastasis (TNM) clinicopathological parameters, followed by statistical analysis. Higher protein expression of NF-κB/p65 in the cytoplasm of tumor tissues compared with adjacent normal mucosa was reported; this increment was positively associated with all clinicopathological parameters, except for tumor localization site. The selected genes demonstrated a diverse associative pattern when analyzed with clinicopathological parameters. CCND1 was positively associated with all TNM parameters and BCL2 was negatively associated with all TNM parameters, thus indicating their importance as strong molecular biomarkers for CRC. According to these results, not all selected genes regulated by NF-κB/p65 show increased expression during CRC development, whereas the transcription factor did. The present study suggests that NF-κB/p65 overexpression is necessary for CRC establishment and progression, but its transcriptional activity is not sufficient to regulate all target genes in CRC. NF-κB/p65 and the gene expression profiles reported in the present study may be therapeutically useful. Considering the heterogeneity of the disease, the particular evaluation of these molecules may allow for the selection of proper diagnosis, treatment and follow-up for patients with sporadic CRC.