F. de la Portilla

Expanded allogeneic adipose-derived stem cells (eASCs) for the treatment of complex perianal fistula in Crohn's disease: results from a multicenter phase I/IIa clinical trial.

PurposeThe management of perianal fistula in patients with Crohn’s disease is an extremely challenging medical problem as many fistulas do not respond to available treatments. The objectives were to assess the safety and efficacy of a suspension of expanded adipose-derived allogeneic mesenchymal stem cells (eASCs) for the treatment of complex perianal fistula in Crohn’s diseaseMethodsAn open-label, single-arm clinical trial was conducted at six Spanish hospitals. Twenty-four patients were administered intralesionally with 20 million eASCs in one draining fistula tract. A subsequent administration of 40 million eASCs was performed if fistula closure was incomplete at week 12. Subjects were followed until week 24 after the initial administration.ResultsTreatment-related adverse events did not indicate any clinical safety concerns after 6xa0months follow-up. The full analysis of efficacy data at week 24 showed 69.2xa0% of the patients with a reduction in the number of draining fistulas, 56.3xa0% of the patients achieved complete closure of the treated fistula achieved, and 30xa0% of the cases presenting complete closure of all existing fistula tracts. Of note, closure was strictly defined as: absence of suppuration through the external orifice and complete re-epithelization, plus absence of collections measured by magnetic resonance image scan (MRI). Furthermore, MRI Score of Severity showed statistically significant differences at week 12 with a marked reduction at week 24.ConclusionsLocally injected eASCs appear to be a simple, safe, and beneficial therapy for perianal fistula in Crohn’s disease patients. Additional studies are needed to further confirm the efficacy of the eASCs.

Evaluation of the use of PTQTMimplants for the treatment of incontinent patients due to internal anal sphincter dysfunction

Objectiveu2002 This study reports the results of injectable silicone PTQTM implants for faecal incontinence due to internal anal sphincter (IAS) dysfunction.

Long-term efficacy of dextranomer in stabilized hyaluronic acid (NASHA/Dx) for treatment of faecal incontinence

AIMnRandomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long-term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12 months after treatment. The objective of this study was to evaluate the long-term efficacy and safety of NASHA/Dx, assessed 24 months after treatment.nnnMETHODnThis study was a 24-month follow-up assessment of patients treated with NASHA/Dx under open-label conditions. Data on FI episodes and quality of life measures were collected from diaries over the 28-day period immediately preceding the 24-month assessment. Adverse events were collected.nnnRESULTSnEighty-three of 115 patients completed the 24-month follow-up assessment. At 24 months, 62.7% of patients were considered responders and experienced a ≥ 50% reduction in the total number of FI episodes. The median number of FI episodes declined by 68.8% (P < 0.001). Episodes of both solid and liquid stool incontinence decreased. The mean number of incontinence-free days increased from 14.6 at baseline to 21.7 at 24 months (P < 0.001). Incontinence scores and FI quality of life scores also showed significant improvements. The most common adverse events (AEs) were proctalgia (13.3%) and pyrexia (9.6%). The majority of AEs were mild to moderate, self-limited and resolved within 1 month of the injection.nnnCONCLUSIONnNASHA/Dx is safe, effective and durable over a 24-month period with a majority of patients experiencing significant improvement in multiple symptoms associated with FI.Randomized, controlled trials have demonstrated the efficacy and safety of injectable bulking agents for the treatment of faecal incontinence (FI), although the long‐term outcome has not been assessed. NASHA/Dx gel, a biocompatible, nonallergenic bulking agent consisting of nonanimal stabilized hyaluronic acid and dextranomer microspheres, has demonstrated efficacy and safety for up to 12 months after treatment. The objective of this study was to evaluate the long‐term efficacy and safety of NASHA/Dx, assessed 24 months after treatment.

The Rabbit as an Animal Model for Proctology Research: Anatomical and Histological Description

ABSTRACT Purpose: This study was designed to describe the surgical anatomy and histology of the rabbit anorectum comparing it to that of humans, in order to decide whether it can be a good experimental model for research in proctology. Material and Methods: This study of the anorectal region was performed on six female New Zealand white rabbits, weighting between 2.5–2.9 kg. An autopsy was performed immediately after sacrificing the animal and an anatomical and histological description was performed. Results: The mean rectum and anal canal lengths were of 7.2 cm and 0.9 cm, respectively. The macroscopic study showed that the musculature of the anal canal is formed by the coccygeus muscle, which serves as puborectalis in humans. It also defined an external anal sphincter with a deep and superficial portion. The histological evaluation showed similarity to that of humans, with mucosa of simple columnar type, muscularis mucosae, a small submucosa, with a muscular wall divided into internal and external layers, separated by the myenteric plexus. Conclusion: The great similarity to both the anatomy and the histology of humans, appropriate size and easy-handling and care, make the rabbit an attractive animal for the use as experimental and research model in proctology.

Gore Bio-A® Fistula Plug for complex anal fistula: the results should be interpreted cautiously

Dear Sir, We are grateful for the comments made by Stelzner et al. [1] regarding our article ‘Outcome of extralevator abdominoperineal excision compared with standard surgery: results from a single centre’ [2]. We agree that case mix and variations in surgical technique may be two important explanations for the diverging results in the literature. It is also possible that some degree of heterogeneity due to case mix is present in our study. We have performed a subgroup analysis that included only tumours located within 4 cm from the anal verge. The results in this subgroup did not differ from those in the entire group, but the perforation rate was higher in the extralevator abdominoperineal excision (ELAPE) group compared with some other series [3,4], and we congratulate those authors on their good results. The results of standard APE in our study showed low rates of circumferential resection margin involvement compared with figures reported for controls in some other studies [3–5]. Again case mix could in part explain these results. In conclusion, although pooled data [6] indicate superiority to extended APE, our results with a higher number of wound revisions indicate that improvements in the technique could be made. Regardless of the method of reconstruction there are a considerable number of patients with wound complications after ELAPE [5,7,8]. These issues should be addressed, as should details of when to apply the technique, to achieve results that are acceptable in all perspectives.

Microstructural, mechanical, and histological evaluation of modified alginate-based scaffolds.

Scaffolds are three-dimensional structures used for tissue regeneration being the base in tissue engineering. These scaffolds are obtained from natural and/or synthetic polymers and they should satisfy some specific requirements such as biocompatibility, suitable mechanical, and microstructural properties to favor cellular adhesion and neovascularization. This work shows a preclinic study about the production of low and medium molecular weight alginate through the use of calcium salts (calcium glutamate). The results showed prove that better structures, distribution, and pore sizes as well as better mechanical properties correspond to medium molecular weight alginate and higher calcium salts concentration. This type of scaffold, after muscular cells cultivation, has been proved as an excellent material for muscle growth. The histopathological analysis shows a low inflammatory response, without a foreign body reaction, suitable neovascularization and good fibroblasts incorporation.

Treatment of transsphincteric fistula-in-ano with growth factors from autologous platelets: results of a phase II clinical trial

PurposeThe aim of this paper is to evaluate to the safety, feasibility and efficacy of a novel treatment for transsphincteric cryptoglandular fistula: injection of autologous plasma rich in growth factors (PRGF) into the fistula tract accompanied by sealing using a fibrin plug created from the activated platelet-poor fraction of the same plasma.MethodThis article is a prospective, phase II clinical trial. The procedure was externally audited. Thirty-six patients diagnosed with transsphincteric fistula-in-ano were included. All patients underwent follow-up examinations at 1xa0week and again at 3, 6 and 12 months after discharge. Main outcome measures safety (number of adverse events), feasibility and effectiveness of the treatment.ResultsA total of 36 patients received the study treatment, with the procedure found to be feasible in all patients. A total of seven adverse events (AE) related to the injected product or surgical procedure were identified in 4 of 36 patients. At the end of the follow-up period (12 months), 33.3% of patients (12/36) had achieved complete fistula healing and 11.1% of patients (4/36) had achieved partial healing. In total, this amounted to 44.4% of patients (16/36) being asymptomatic at final follow-up. In successfully healed patients, a gradual reduction in pain was observed, as measured using a Visual Analog Scale (VAS) (pxa0=xa00.0278). Compared to baseline, a significant improvement in Wexner score was seen in patients achieving total or partial healing of the fistula (pxa0=xa00.0195).ConclusionsThe study treatment was safe and feasible, with apparently modest efficacy rates. Continence and pain improvement following treatment may be considered predictive factors for healing.

Is the interval from surgery to ileostomy closure a risk factor for low anterior resection syndrome

Low anterior resection syndrome (LARS) comprises a collection of symptoms affecting patients after restorative surgery for rectal cancer. The aim of the present study was to analyse the incidence of LARS in patients undergoing rectal cancer surgery with and without subsequent ileostomy and to determine whether the interval to ileostomy closure is a factor associated with its occurrence.

Anti-Inflammatory Local Effect of Hydroxytyrosol Combined with Pectin-Alginate and Olive Oil on Trinitrobenzene Sulfonic Acid-Induced Colitis in Wistar Rats

ABSTRACT Purpose: Evaluate the efficacy of hydroxytyrosol in the local treatment of inflammatory colitis. Currently, the existing treatments for inflammatory bowel diseases does not cure the disease and it is associated with high rates of side effects and complications. Hydroxytyrosol is a phenyl-ethyl-alcohol derived from the hydrolysis of oleuropein and present in olive oil, previous studies have demonstrated the anti-inflammatory effect of dietary hydroxytyrosol supplement, with no toxicity. Materials & Methods: Colitis has been induced by using Trinitrobenzene Sulfonic Acid at 40 rats. They were divided into four groups randomly: 10 rats without treatment; 10 rats with pectin/alginate mixture; 10 rats treated with pectin/alginate + olive oil; 10 rats treated with pectin/alginate + olive oil + hydroxytyrosol. Animals were sacrificed 10 days after induction of trinitrobenzene sulfonic acid, receiving 5 days of continuous treatment. Samples of the rectal area were studied and observed under a microscope to determine the damage by Hunter scoring modified, assessing inflammatory infiltration, number of intestinal walls involved, damage to the mucosal architecture, and edema. Results: When the rectum was analyzed in a global way, nonsignificant differences were observed; however, when performing an individualized analysis, statistically significant differences in the inflammatory infiltrate are present in the samples, which were evaluated using the ANOVA and Student-T statistics. Conclusions: Local treatment with the natural antioxidant hydroxytyrosol combined with pectin/alginate and olive oil of inflammatory bowel disease has been shown to be effective against inflammatory infiltration of TNBS-induced colitis.

Ultrasonographic evidence of Gatekeeper™ prosthesis migration in patients treated for faecal incontinence: a case series

BackgroundFaecal incontinence (FI) is both a medical and social problem, with an underestimated incidence. For patients with internal anal sphincter damage, implantation of biomaterial in the anal canal is a recognised treatment option. One such material, Gatekeeper™, has previously shown promising short- and medium-term results without any major complications, including displacement. The main aim of the present study is to assess the degree to which displacement of Gatekeeper prostheses may occur and to determine whether this is associated with patient outcomes.MethodsSeven patients (six females) with a mean age of 55.6xa0years [50.5–57.2] and a mean FI duration of 6xa0±xa02xa0years were prospectively enrolled in the study. Each subject was anaesthetised and underwent implantation of six prostheses in the intersphincteric region, guided by endoanal 3D ultrasound (3D-EAU). Follow-up was performed at post-interventional months 1, 3, and 12 (median 12xa0±xa04xa0months), during which data were obtained from a defaecation diary, Wexner scale assessment, anorectal manometry (ARM), 3D-EAU, and a health status and quality of life questionnaire (FIQL).ResultsAt 3-month follow-up, 3D-EAU revealed displacement of 24/42 prostheses in 5/7 patients. Of these, 15 had migrated to the lower portion and 9 to the upper portion of the anal canal and rectum. Despite this migration, treatment was considered successful in 3/7 patients. In one patient, it was necessary to remove a prosthesis due to spontaneous extrusion.ConclusionsWe have shown that displacement of the Gatekeeper™ prosthesis occurs, but is not associated with poorer clinical outcomes.