Treatment of faecal incontinence with autologous expanded mesenchymal stem cells: results of a pilot study.

AIM: Management of faecal incontinence (FI) remains challenging because no definitive optimal treatment for this condition has yet been determined. Regenerative medicine could be an attractive therapeutic alternative for treating FI. Here, we aimed to determine the safety and feasibility of autologous expanded mesenchymal stem cells derived from adipose tissue (AdMSCs) in the treatment of patients diagnosed with structural FI. METHOD: This was a randomized, multicentre, triple-blinded, placebo-controlled pilot study conducted at four sites in Spain with 16 adults with FI and a sphincter defect. Autologous AdMSCs were obtained from patients from surgically excised adipose tissue. These patients were intralesionally infused with a single dose of 4 × 107 AdMSCs or a placebo while under anaesthesia. We assessed the safety and feasibility of the treatment as the cumulative incidence of adverse events and the treatment efficacy using the Cleveland Clinic Faecal Incontinence Score, Faecal Incontinence Quality of Life score and Starck criteria to classify sphincter defects and anorectal physiology outcomes. RESULTS: Adipose tissue extraction, cell isolation and intralesional infusion procedures were successful in all the patients. There was only one adverse event connected to adipose tissue extraction (a haematoma), and none was associated with the injection procedure. There were no significant differences in any of the assessed clinical, manometric or ultrasonographic parameters. CONCLUSION: This study indicates that this infusion procedure in the anal sphincter is feasible and safe. However, it failed to demonstrate efficacy to treat patients with structural FI.

Platelet-rich plasma (PRP) versus fibrin glue in cryptogenic fistula-in-ano: a phase III single-center, randomized, double-blind trial.

PURPOSE: To compare the clinical outcome of autologous platelet-rich growth factor (PRP) with commercial fibrin glue in the management of high cryptogenic fistulae-in-ano. METHOD: The study was conducted at a single center between July 2012 and July 2015 and performed as a phase III, randomized, double-blind comparison of autologously prepared PRP versus fibrin glue for cryptoglandular anal fistulae without active sepsis. Patients were assessed with clinical and endosonographic follow-up. Patients were followed up at 1 week and then at 3, 6, and 12 postoperative months. The primary outcome measure was the fistula healing rate (complete, partial, and non-healing) with secondary outcome measures assessing fistula recurrence, continence status, quality of life, and visual analog pain scores. RESULTS: Of the 56 enrolled patients, 32 were PRP-treated and 24 were fibrin-treated. The groups were well matched for fistula type with an improved overall healing rate for PRP-treated over fibrin-treated cases (71% vs. 58.3%, respectively; P = 0.608); a complete healing rate of 48.4% vs. 41.7%, respectively; and a partial healing rate of 22.6% vs. 16.7%, respectively. The median pain scores of PRP-treated patients were lower at the first visit with a greater initial pain decrease early during follow-up. Improvements in pain reduction impacted the quality of life measures (P = 0.035). All adverse events were minor and no patient experienced a negative impact on continence. CONCLUSION: Treatment of complex cryptoglandular anal fistula with autologous PRP is as effective as fibrin glue with less cost and no adverse effect on continence.

Local Mesenchymal Stem Cell Therapy in Experimentally Induced Colitis in the Rat.

BACKGROUND: Multipotent mesenchymal stem cells (MSCs) have been used in inflammatory bowel diseases because of their immunomodulatory and regenerative properties. We investigated their local use in an experimental model of colitis in the rat. MATERIALS AND METHODS: Colitis was induced into 20 Wistar rats with local TNBS instillation. Allogeneic stem cells were derived from rat adipose tissue and labeled with PKH2 linker dye with creation of a control and a second group treated by a local injection into the rectal wall of 2×106 allogeneic adipose tissue-derived stem cells (ADSCs). The thicknesses of different components of the rectum were measured with comparisons made in different parts of the colon of the Hunter inflammatory score. PKH2-dyed ADSCs were detected by fluorescence microscopy. RESULTS AND CONCLUSIONS: Total colitis was induced in 19/20 rats with homing of fluorescent ADSCs. to the crypt base and perivascular space of the submucosa. There were no differences in component rectal wall thicknesses with a higher Hunter score in the treated group compared with the controls, in the rectum (3.8±2.74 vs. 1.5±2.37, respectively; p=0.017) and in right colon (2.5±1.08 vs. 0.20±0.42, respectively; p=0.0001). Local colonic injection of allogeneic adipose stem cells. in experimental colitis is feasible and safe. There is demonstrable homing of cells in chemically-induced colitis both to the treated region and parts of the colon distant to the MSC treatment site. Such cells readily proliferate in vitro and could potentially be a source for future treatment of resistant disease.

Factibility and security study of the PICS-AF™ plug for the treatment of cryptoglandular anal fistula. / Estudio de factibilidad y seguridad del plug de colágeno (PICS-AF™) en el tratamiento de la fístula anal criptoglandular.

INTRODUCTION: The PICS-AF™ (Curaseal Inc.) device is a new plug made of collagen that has a retention system in the internal orifice. This pilot study was designed to assess both the feasibility and safety of this plug in the treatment of trans-sphincteric anal fístulas. METHODS: A total of 44 patients (34 men), with a mean age of 54.68±7.3, with trans-sphincteric anal fístulas were included in the study; 34 of them were analyzed. All patients were examined according to a strict preoperative protocol and until 6 months after surgery. The feasibility of the procedure and the adverse events were analyzed. RESULTS: Finally, 34 patients were operated on, and in 30 of them the plug was used. Therefore, the feasibility was calculated at 88%. There was a total of 16 adverse events, 4recorded as not related (3 mild and one moderate) and 12 related to the procedure or to the device implanted. Of these, 5were mild, 5moderate and 2severe. The majority of the events reported were related to proctalgia (4 patients) or infection at the implant site (4 patients). CONCLUSIONS: The present study indicates that the new collagen plug can be placed effectively and with an acceptable complication rate.

Estudio de factibilidad y seguridad del plug de colágeno (PICS-AF(TM)) en el tratamiento de la fístula anal criptoglandular / Factibility and security study of the PICS-AF(TM) plug for the treatment of cryptoglandular anal fistula

INTRODUCCIÓN: El dispositivo PICS-AF(TM) es un nuevo tapón hecho de colágeno que tiene un sistema de retención en el orificio fistuloso interno. Este estudio piloto ha sido diseñado para evaluar la factibilidad y seguridad de este dispositivo en el tratamiento de las fístulas anales criptoglandulares transesfinterianas. MÉTODOS: Un total de 44 pacientes (34 hombres) con diagnóstico de fístula transesfinteriana fueron incluidos en el estudio, de los cuales 34 fueron seleccionados. Todos los pacientes fueron examinados según un protocolo estricto antes de la cirugía y hasta 6 meses después. Se analizaron la factibilidad del procedimiento y los acontecimientos adversos. RESULTADOS: El dispositivo se colocó sin incidencias en 30 de los 34 pacientes (factibilidad del 88%). Se evidenciaron un total de 16 acontecimientos adversos, 4registrados como no relacionados con el procedimiento (3 leves y uno moderado) y 12 relacionados con el procedimiento o el dispositivo implantado. De ellos, 5fueron leves, 5moderados y 2graves. La mayoría de los efectos adversos reportados fueron proctalgia (4 pacientes) o infección en el sitio del implante (4 pacientes). CONCLUSIONES: El presente estudio indica que el nuevo tapón de colágeno puede ser colocado de forma efectiva y con una tasa de complicaciones aceptable

INTRODUCTION: The PICS-AF(TM) (Curaseal Inc.) device is a new plug made of collagen that has a retention system in the internal orifice. This pilot study was designed to assess both the feasibility and safety of this plug in the treatment of trans-sphincteric anal fístulas. METHODS: A total of 44 patients (34 men), with a mean age of 54.68±7.3, with trans-sphincteric anal fístulas were included in the study; 34 of them were analyzed. All patients were examined according to a strict preoperative protocol and until 6 months after surgery. The feasibility of the procedure and the adverse events were analyzed. RESULTS: Finally, 34 patients were operated on, and in 30 of them the plug was used. Therefore, the feasibility was calculated at 88%. There was a total of 16 adverse events, 4recorded as not related (3 mild and one moderate) and 12 related to the procedure or to the device implanted. Of these, 5were mild, 5moderate and 2severe. The majority of the events reported were related to proctalgia (4 patients) or infection at the implant site (4 patients). CONCLUSIONS: The present study indicates that the new collagen plug can be placed effectively and with an acceptable complication rate

Validation of a new scoring system: Rapid assessment faecal incontinence score.

AIM: To implement a quick and simple test - rapid assessment faecal incontinence score (RAFIS) and show its reliability and validity. METHODS: From March 2008 through March 2010, we evaluated a total of 261 consecutive patients, including 53 patients with faecal incontinence. Demographic and comorbidity information was collected. In a single visit, patients were administered the RAFIS. The results obtained with the new score were compared with those of both Wexner score and faecal incontinence quality of life scale (FIQL) questionnaire. The patient without influence of the surgeon completed the test. The role of surgeon was explaining the meaning of each section and how he had to fill. Reliability of the RAFIS score was measured using intra-observer agreement and Cronbach's alpha (internal consistency) coefficient. Multivariate analysis of the main components within the different scores was performed in order to determine whether all the scores measured the same factor and to conclude whether the information could be encompassed in a single factor. A sample size of 50 patients with faecal incontinence was estimated to be enough to detect a correlation of 0.55 or better at 5% level of significance with 80% power. RESULTS: We analysed the results obtained by 53 consecutive patients with faecal incontinence (median age 61.55 ± 12.49 years) in the three scoring systems. A total of 208 healthy volunteers (median age 58.41 ± 18.41 years) without faecal incontinence were included in the study as negative controls. Pearson's correlation coefficient between "state" and "leaks" was excellent (r = 0.92, P < 0.005). Internal consistency in the comparison of "state" and "leaks" yielded also excellent correlation (Cronbach's α = 0.93). Results in each score were compared using regression analysis and a correlation value of r = 0.98 was obtained with Wexner score. As regards FIQL questionnaire, the values of "r" for the different subscales of the questionnaire were: "lifestyle" r = -0.87, "coping/behaviour" r = -0.91, "depression" r = -0.36 and "embarrassment" r = -0.90, (P < 0.01). A multivariate analysis showed that all the scoring systems measured the same factor. A single factor may explain 80.84% of the variability of FI, so all the scoring systems measure the same factor. Patient's continence improves when RAFIS and Jorge-Wexner scores show low values and when the values obtained in the FIQL questionnaire are high. CONCLUSION: RAFIS is a valid and reliable tool to assess Faecal Incontinence.