Cristián Gallardo interviews Lilli Lundby, Consultant Colorectal Surgeon, Department of Surgery and Pelvic Floor Unit at the Aarhus University Hospital in Denmark.

Cristián Gallardo: Dear Dr Lundby, first of all thank you for agreeing to speak with us about such an important subject: the management of complex anal fistulas mainly in Crohn’s disease patients.

Lilli Lundby: Thank you for the invitation. Surgical treatment of complex anal fistulas is a challenge and it is a great pleasure to get the opportunity to talk about how we manage these patients in our centre.

CG: We would like to begin by asking you to give a brief summary of the main approach to complex anal fistulas at your centre.

LL: Our department is a tertiary centre for complex anal fistulas and we receive more than 300 new referrals annually for patients with anal fistulas.

The overall treatment strategy for complex anal fistulas is to eliminate the sepsis, simplify the complexity of the fistula and then permanently close the fistula without any damage to the anal sphincter function.

Our first approach is to examine the patient under general anaestesia including anal endosonography and make a plan for further treatment of the fistula. In some cases MRI can be helpful. In order to prepare the fistula for final closure, a loose seton will be placed and repeated curettage and revisions will be performed until the secretory activity is reduced.

For patients with Crohn's disease (CD) collaboration with gastroenterologists is very important. In MDT conferences we discuss all patients with complicated perineal CD and ensure that the medical treatment is optimal.

When the fistula is suitable for an attempt at final closure, the surgical procedure will be tailored to the anatomical structure of the fistula. The optional sphincter-preserving procedures in our department are LIFT, plug, advancement flap, VAAFT and injection of freshly collected autologous adipose tissue.

CG: We have seen with great expectation the results published by you and your colleagues using freshly collected autologous adipose tissue in anal fistula patients. In relation to this, which patients are you specially treating with this technique?

LL: Since 2015 we have used injection of freshly collected adipose tissue for patients with cryptoglandular origin of the fistula, selected anovaginal fistulas and for patients with Crohn’s disease. Generally, the procedure is suited for fistulas where sphincter-saving procedures are an option.

However, in cases where the fistula has been revised several times due to extensions or multiple tracts and the tissue in the anal canal is very fibrotic with a wide internal opening, injection of autologous adipose tissue is the preferred method.

In special cases of very active complex fistulas we use autologous adipose tissue to accelerate the healing process and reduce inflammation and secretion without attempting to close the internal opening.

CG: What are the main results obtained using this new technique?

LL: Injection of autologous adipose tissue is an important supplement to other sphincter-saving procedures. The success rate of fistula closing is, in general, very difficult to compare among centres because the definition of fistula healing varies significantly. In our clinic we use very strict criteria for fistula healing defined as no symptoms of discharge, and no visible external and no palpable internal opening. Furthermore, fistula healing on MRI is defined as having no signs of a fluid-conducting tract. The healing rates after injection of freshly harvested autologous adipose tissue are currently comparable to other methods using cultivated stem cells. With continuous technical improvements of the procedure we will expect even better results in future analyses.

CG: As you know, treatment of perianal fistulas with cultured mesenchymal stem cells derived from adipose tissue or allogeneic adipose-derived stem cells has shown promising results in both Crohn's disease (CD) patients and non-CD patients. What are the main advantages of this new technique, the injection of freshly collected autologous adipose tissue, over previous techniques?

LL: First, the freshly collected adipose tissue is easily available in most patients and it needs only a minimum of preparation before being ready for injection. Second, the treatment including liposuction, closure of the internal opening and injection of the prepared adipose tissue only requires a single surgical procedure lasting about 60 minutes. Third, there is no need for laboratory facilities and cell culture. Forth, the procedure is inexpensive as it in total only costs approximately 1000€.

CG: What, from your point of view, is the mechanism of healing of this technique?

LL: Cleaning of the fistula tract with removal of all the granulation tissue and a meticulous closure of the internal opening are very important factors in providing optimal healing conditions. Adipose-derived mesenchymal stem cells are believed to be the active components in adipose tissue, able to release bioactive and immunomodulatory substances that can promote tissue repair and thus healing of the fistula. However, there is still many unanswered questions about mechanism of action of this technique.

CG: In comparison to other alternatives such as using either cultured autologous or allogeneic adipose-derived stem cells, does the use of freshly collected adipose tissue achieve a reasonable number of stromal (mesenchymal) stem cells?

LL: We have performed some studies (unpublished) characterising the adipose tissue prepared for injection. The investigated samples of freshly harvested and prepared adipose tissue contain mature adipocytes, a mixture of living stromal cells, stromal stem cells, endothelial cells and immune cells. The number of stem cells in the sample is dependent on how the fat is prepared. However, our investigations indicate that the amount of mesenchymal stem cells vary between 10% to 50% of the stromal vascular fraction obtained from liposuction. Further studies will show if it is possible to increase the concentration of stem cells in the prepared fat for injection.

CG: Do you think this technique is safe and reproducible?

LL: The procedure is safe and feasible. We have not seen deterioration of the functional outcome scores postoperatively. The number of complications is acceptable (5%) and the most common serious complication is development of an abscess. The reproducibility of the results still has to be investigated in future studies

CG: What are the future prospects for the procedure?

LL: I believe that regenerative therapies will play an important role in the future treatment for anal fistulas. Cell therapy is a rapidly growing area of research. There is still a lot of unanswered question especially concerning the mechanism of action and there is a great potential for improvements of the technique and thus for improvement of the successrates for fistula healing.

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