Observational Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2015; 21(11): 3330-3336
Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3330
Recurrent anal fistulae: Limited surgery supported by stem cells
Damian Garcia-Olmo, Hector Guadalajara, Ines Rubio-Perez, Maria Dolores Herreros, Paloma de-la-Quintana, Mariano Garcia-Arranz
Damian Garcia-Olmo, Hector Guadalajara, Maria Dolores Herreros, Mariano Garcia-Arranz, Hospital Fundación Jimenez Díaz, IIS-FJD, 28040 Madrid, Spain
Damian Garcia-Olmo, Maria Dolores Herreros, Colorectal Surgery Unit, University Hospital Fundación JiménezDíaz, 28040 Madrid, Spain
Ines Rubio-Perez, Paloma de-la-Quintana, Colorectal Surgery Unit, La Paz University Hospital, 28046 Madrid, Spain
Mariano Garcia-Arranz, Cell Therapy Laboratory, University Hospital Fundación Jiménez Díaz, 28040 Madrid, Spain
Author contributions: Garcia-Olmo D and Guadalajara H contributed equally to the design of the study, performed the surgical procedures, and acquired and analyzed all data, supervised the project, and wrote the first draft of the paper; Rubio-Perez I collaborated in the analysis and interpretation of data, critically revised the main text and content, and wrote the final version of the paper; Herreros MD collaborated in design and conception of the study and performed the surgical interventions; de-la-Quintana P contributed to the first acquisition of data from patients in the outpatient clinics and their analysis; Garcia-Arranz M provided cell resources and managed all regulatory and legal aspects related to the study, participating in design and conception, and contributed to the revision of contents related to cell behavior and physiology; all authors revised and approved the final version to be published.
Ethics approval: This work recruited patients under a Compassionate-use Program, which is legislated by the Royal Spanish Decree 1015/2009, 19th of July. We had to make an individual request for every patient to the Spanish Agency for Medicines and Health Products (AEMPS).
Informed consent: Consents were signed by the attending surgeons and the patients.
Conflict-of-interest: García-Olmo D and Garcia-Arranz M, have applied for two patents related with this study entitled “Identification and isolation of multipotent cells from non-osteochondral mesenchymal tissue” (WO 2006/057649) and “Use of adipose tissue-derived stromal stem cells in treating fistula” (WO 2006/136244). García-Olmo D is a member of the Advisory Board of Tigenix SAU. This manuscript has not been published nor has been presented as a podium/poster presentation in a scientific meeting.
Data sharing: Participants gave informed consent for sharing of patient data. The risk of identification is very low, as the research is committed to keeping the anonymity of the patients.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hector Guadalajara, MD, PhD, Hospital Fundación Jimenez Díaz, IIS-FJD, Avda, Reyes Católicos 2, 28040 Madrid, Spain. hector.guadalajara@fjd.es
Telephone: +34-91-5504822 Fax: +34-91-5504849
Received: October 2, 2014
Peer-review started: October 3, 2014
First decision: October 29, 2014
Revised: November 18, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: March 21, 2015

AIM: To study the results of stem-cell therapy under a Compassionate-use Program for patients with recurrent anal fistulae.

METHODS: Under controlled circumstances, and approved by European and Spanish laws, a Compassionate-use Program allows the use of stem-cell therapy for patients with very complex anal fistulae. Candidates had previously undergone multiple surgical interventions that had failed to resolve the fistulae, and presented symptomatic recurrence. The intervention consisted of limited surgery (with closure of the internal opening), followed by local implant of stem cells in the fistula-tract wall. Autologous expanded adipose-derived stem cells were the main cell type selected for implant. The first evaluation was performed on the 8th postoperative week; outcome was classified as response or partial response. Evaluation one year after the intervention confirmed if complete healing of the fistula was achieved.

RESULTS: Ten patients (8 male) with highly recurrent and complex fistulae were treated (mean age: 49 years, range: 28-76 years). Seven cases were non-Crohn’s fistulae, and three were Crohn’s-associated fistulae. Previous surgical attempts ranged from 3 to 12. Two patients presented with preoperative incontinence (Wexner scores of 12 and 13 points). After the intervention, six patients showed clinical response on the 8th postoperative week, with a complete cessation of suppuration from the fistula. Three patients presented a partial response, with an evident decrease in suppuration. A year later, six patients (60%) remained healed, with complete reepithelization of the external opening. Postoperative Wexner Scores were 0 in six cases. The two patients with previous incontinence improved their scores from 12 to 8 points and from 13 to 5 points. No adverse reactions or complications related to stem-cell therapy were reported during the study period.

CONCLUSION: Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases, sparing fecal incontinence risk, and improving previous scoring.

Keywords: Adipose-derived stem cells, Cell therapy, Compassionate use, Crohn’s disease, Fistula-in-ano

Core tip: Our group has performed various clinical trials with adipose stem cells. Patients with very complex fistulae, multiple previous surgeries, and treatment failure are generally not able to enter these studies despite the benefit and “last chance” of cure. We present the results of a Compassionate-use Program, which enabled the application of stem-cell therapy to these patients, under strict regulations. Ten patients were treated, and after one year of follow-up, we conclude that adipose stem cells are effective and safe, and 60% of the patients achieved complete healing.