Advertisement

Techniques in Coloproctology

, Volume 22, Issue 2, pp 107–113 | Cite as

Micro-fragmented adipose tissue injection for the treatment of complex anal fistula: a pilot study accessing safety and feasibility

  • G. Naldini
  • A. Sturiale
  • B. Fabiani
  • I. Giani
  • C. Menconi
Original Article

Abstract

Background

The aim of the present study was to evaluate the safety and efficacy of autologous, micro-fragmented and minimally manipulated adipose tissue injection associated closure of the internal opening in promoting healing of complex anal fistula.

Methods

A pilot study was conducted on patients referred to our center with anal fistula, from April 2015–December 2016. Inclusion criteria were age over 16 years old and a diagnosis of complex anal fistula according to the American Gastroenterological Association classification The patients were divided into 2 groups; the “first time group” (Group I) in which micro-fragmented adipose tissue injection with closure of the internal opening was the first sphincter-saving procedure, and the “recurrent group” (Group II) consisting of patients who had failed prior sphincter-saving procedures. The procedure was carried out 4–6 weeks after seton placement. Follow-up visits were scheduled at 7 days, and 1, 3, 6 and 12 months after surgery. Fistula healing was defined as the closure of the internal and external openings without any discharge.

Results

Out of 47 patients with complex transsphincteric anal fistula, 19 met the inclusion criteria and were selected to undergo the procedure. Twelve of these patients (Group I) had micro-fragmented adipose tissue injection as first-line treatment, and 7 (Group II) had failed previous sphincter-saving procedures. The mean operative time was 55 ± 6 min (range 50–70 min). The mean postoperative pain score measured with the visual analog pain scale was 2 ± 1.4 (range 0–4). No intraoperative difficulties related to the use of the kit were recorded. There were no cases of postoperative fever or abdominal sepsis related to the procedure and no post-treatment perianal bleeding or impaired anal continence. Only 3 cases of minor abdominal wall hematoma that did not require any treatment and 1 case of perianal abscess were observed. Patients were evaluated for a mean follow-up time of 9 ± 3.1 months (range 3–12 months). The overall healing rate was 73.7, 83.3% for Group I and 57.1% for Group II.

Conclusions

The injection of autologous, micro-fragmented and minimally manipulated adipose tissue associated with closure of the internal opening is a safe, feasible and reproducible procedure and may enhance complex anal fistula healing.

Keywords

Adipose tissue Anal Canal Muscles Lipogems Fistula Lipectomy 

Notes

Authors’ contribution

GN, AS and IG contribute to the conception and of the study and to the drawing up of the manuscript; AS, IG and BF contribute to the data acquisition, analysis and interpretation; AS, CM and GN contribute to the critical revision of the manuscript and to the approval of the version to be published.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

Supplementary material 1 (MP4 157885 kb)

References

  1. 1.
    Zanotti C, Martinez-Puente C, Pascual I, Pascual M, Herreros D, Garcia-Olmo D (2007) An assessment of the incidence of fistula-in-ano in four countries of the European Union. Int J Colorectal Dis 22(12):1459–1462CrossRefPubMedGoogle Scholar
  2. 2.
    American Gastroenterological Association (2003) American Gastroenterological Association medical position statement: perianal Crohn’s disease. Gastroenterology 125(5):1503–1507CrossRefGoogle Scholar
  3. 3.
    Farmer RG, Hawk WA, Turnbull RB Jr (1975) Clinical patterns in Crohn’s disease: a statistical study of 615 cases. Gastroenterology 68(4 Pt 1):627–635PubMedGoogle Scholar
  4. 4.
    Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB (2003) AGA technical review on perianal Crohn’s disease. Gastroenterology 125(5):1508–1530CrossRefPubMedGoogle Scholar
  5. 5.
    Amato A, Bottini C, De NP et al (2015) Evaluation and management of perianal abscess and anal fistula: a consensus statement developed by the Italian Society of Colorectal Surgery (SICCR). Tech Coloproctol 19(10):595–606CrossRefPubMedGoogle Scholar
  6. 6.
    Kontovounisios C, Tekkis P, Tan E, Rasheed S, Darzi A, Wexner SD (2016) Adoption and success rates of perineal procedures for fistula-in-ano: a systematic review. Colorectal Dis 18(5):441–458CrossRefPubMedGoogle Scholar
  7. 7.
    Limura E, Giordano P (2015) Modern management of anal fistula. World J Gastroenterol 21(1):12–20CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gimble JM, Guilak F, Bunnell BA (2010) Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther 1(2):19CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Zuk PA, Zhu M, Ashjian P et al (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zuk PA, Zhu M, Mizuno H et al (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7(2):211–228CrossRefPubMedGoogle Scholar
  11. 11.
    Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9(1):11–15CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Chamberlain G, Fox J, Ashton B, Middleton J (2007) Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 25(11):2739–2749CrossRefPubMedGoogle Scholar
  13. 13.
    Mennigen R, Laukotter M, Senninger N, Rijcken E (2015) The OTSC(R) proctology clip system for the closure of refractory anal fistulas. Tech Coloproctol 19(4):241–246CrossRefPubMedGoogle Scholar
  14. 14.
    Prosst RL, Joos AK, Ehni W, Bussen D, Herold A (2015) Prospective pilot study of anorectal fistula closure with the OTSC Proctology. Colorectal Dis 17(1):81–86CrossRefPubMedGoogle Scholar
  15. 15.
    Prosst RL, Ehni W, Joos AK (2013) The OTSC(R) Proctology clip system for anal fistula closure: first prospective clinical data. Minim Invasive Ther Allied Technol 22(5):255–259CrossRefPubMedGoogle Scholar
  16. 16.
    Dubois A, Carrier G, Pereira B et al (2015) Therapeutic management of complex anal fistulas by installing a nitinol closure clip: study protocol of a multicentric randomised controlled trial–FISCLOSE. BMJ Open 5(12):e009884CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Giordano P, Sileri P, Buntzen S et al (2016) A prospective multicentre observational study of Permacol collagen paste for anorectal fistula: preliminary results. Colorectal Dis 18(3):286–294CrossRefPubMedGoogle Scholar
  18. 18.
    Hammond TM, Porrett TR, Scott SM, Williams NS, Lunniss PJ (2011) Management of idiopathic anal fistula using cross-linked collagen: a prospective phase 1 study. Colorectal Dis 13(1):94–104CrossRefPubMedGoogle Scholar
  19. 19.
    Narang SK, Keogh K, Alam NN, Pathak S, Daniels IR, Smart NJ (2017) A systematic review of new treatments for cryptoglandular fistula in ano. Surgeon 15(1):30–39CrossRefPubMedGoogle Scholar
  20. 20.
    Fabiani B, Menconi C, Martellucci J, Giani I, Toniolo G, Naldini G (2017) Permacol collagen paste injection for the treatment of complex anal fistula: 1-year follow-up. Tech Coloproctol 21(3):211–215CrossRefPubMedGoogle Scholar
  21. 21.
    Caplan AI (2007) Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. J Cell Physiol 213(2):341–347CrossRefPubMedGoogle Scholar
  22. 22.
    Tremolada C, Colombo V, Ventura C (2016) Adipose Tissue and mesenchymal stem cells: state of the art and Lipogems(R) technology development. Curr Stem Cell Rep 2:304–312CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bianchi F, Maioli M, Leonardi E et al (2013) A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant 22(11):2063–2077CrossRefPubMedGoogle Scholar
  24. 24.
    von Heimburg D, Hemmrich K, Haydarlioglu S, Staiger H, Pallua N (2004) Comparison of viable cell yield from excised versus aspirated adipose tissue. Cells Tissues Organs 178(2):87–92CrossRefGoogle Scholar
  25. 25.
    Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173CrossRefPubMedGoogle Scholar
  26. 26.
    Panes J, Garcia-Olmo D, Van AG et al (2016) Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn’s disease: a phase 3 randomised, double-blind controlled trial. Lancet 388(10051):1281–1290CrossRefPubMedGoogle Scholar
  27. 27.
    Herreros MD, Garcia-Arranz M, Guadalajara H, De La Quintana P, Garcia-Olmo D (2012) Autologous expanded adipose-derived stem cells for the treatment of complex cryptoglandular perianal fistulas: a phase III randomized clinical trial (FATT 1: fistula Advanced Therapy Trial 1) and long-term evaluation. Dis Colon Rectum 55(7):762–772CrossRefPubMedGoogle Scholar
  28. 28.
    Garcia-Olmo D, Herreros D, Pascual I et al (2009) Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 52(1):79–86CrossRefPubMedGoogle Scholar
  29. 29.
    Garcia-Arranz M, Herreros MD, Gonzalez-Gomez C et al (2016) Treatment of Crohn’s-related rectovaginal fistula with allogeneic expanded-adipose derived stem cells: a Phase I-IIa clinical trial. Stem Cells Transl Med 5(11):1441–1446CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • G. Naldini
    • 1
  • A. Sturiale
    • 1
  • B. Fabiani
    • 1
  • I. Giani
    • 1
  • C. Menconi
    • 1
  1. 1.Proctological and Perineal Surgery UnitCisanello University HospitalPisaItaly

Personalised recommendations