RESUMEN
BACKGROUND/PURPOSE: Injectable bulking therapy has emerged as a treatment for fecal incontinence (FI), however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic acid with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI. METHODS: Seven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FIQL and SF-36 quality of life questionnaires. RESULTS: Before treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8-52). At 6â¯months, the corresponding figures were 5.3 (median 4, range 0-19, pâ¯=â¯0.018), and at 18â¯months the figures were 4.3 (median 2, range 1-20, pâ¯=â¯0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6â¯months was noted (pâ¯=â¯0.04). No serious adverse events occurred. CONCLUSIONS: NASHA/Dx is a promising treatment option for selected adult patients with persistent FI after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level IV.
Asunto(s)
Malformaciones Anorrectales/complicaciones , Dextranos/uso terapéutico , Incontinencia Fecal , Ácido Hialurónico/análogos & derivados , Adulto , Dextranos/administración & dosificación , Incontinencia Fecal/etiología , Incontinencia Fecal/terapia , Humanos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Inyecciones , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Endoscopic injection of bulking agents has been widely used to treat urinary incontinence, often due to urethral sphincter complex insufficiency. The aim of the study was to develop a novel injectable bioactive collagen-fibrin bulking agent restoring long-term continence by functional muscle tissue regeneration. Fibrin micro-beads were engineered using a droplet microfluidic system. They had an average diameter of 140⯵m and recombinant fibrin-binding insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1) was covalently conjugated to the beads. A plasmin fibrin degradation assay showed that 72.5% of the initial amount of α2PI1-8-MMP-IGF-1 loaded into the micro-beads was retained within the fibrin micro-beads. In vitro, the growth factor modified fibrin micro-beads enhanced cell attachment and the migration of human urinary tract smooth muscle cells, however, no change of the cellular metabolic activity was seen. These bioactive micro-beads were mixed with genipin-crosslinked homogenized collagen, acting as a carrier. The collagen concentration, the degree of crosslinking, and the mechanical behavior of this bioactive collagen-fibrin injectable were comparable to reference samples. This novel injectable showed no burst release of the growth factor, had a positive effect on cell behavior and may therefore induce smooth muscle regeneration in vivo, necessary for the functional treatment of stress and other urinary incontinences. STATEMENT OF SIGNIFICANCE: Urinary incontinence is involuntary urine leakage, resulting from a deficient function of the sphincter muscle complex. Yet there is no functional cure for this devastating condition using current treatment options. Applied physical and surgical therapies have limited success. In this study, a novel bioactive injectable bulking agent, triggering new muscle regeneration at the injection site, has been evaluated. This injectable consists of cross-linked collagen and fibrin micro-beads, functionalized with bound insulin-like growth factor-1 (α2PI1-8-MMP-IGF-1). These bioactive fibrin micro-beads induced human smooth muscle cell migration in vitro. Thus, this injectable bulking agent is apt to be a good candidate for regeneration of urethral sphincter muscle, ensuring a long-lasting treatment for urinary incontinence.
Asunto(s)
Colágeno/química , Reactivos de Enlaces Cruzados/química , Fibrina/uso terapéutico , Inyecciones , Microfluídica/métodos , Microesferas , Incontinencia Urinaria/tratamiento farmacológico , Animales , Movimiento Celular , Supervivencia Celular , Módulo de Elasticidad , Fibrina/farmacología , Humanos , Factor I del Crecimiento Similar a la Insulina , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Tamaño de la Partícula , Ratas , Reología , Incontinencia Urinaria/patología , ViscosidadRESUMEN
Many patients with fecal incontinence respond to conservative measures based upon a careful assessment and a multimodality approach that Is within the expertise of the practicing gastroenterologist. However, there Is a need for new and effective strategies when conservative therapy fails. This article reviews established therapies for fecal incontinence, such as biofeedback, as well as new therapies that have been approved by the US Food and Drug Administration (FDA), such as sacral neuromodulation and an injectable bulking agent. Also reviewed are some of the newer approaches that have not yet been approved by the FDA or that have uncertain efficacy.