Introduction

Anal fistulas remain a challenge to surgeons because of their high recurrence rate.¹ A refractory disease course might prompt multiple surgical interventions with possible risk of damage to the anal sphincters with subsequent faecal incontinence. Therefore, patients should receive conservative treatment.² Consequently, at present, several sphincter-saving methods are offered, such as mucosal advancement flap (MAF) and ligation of intersphincteric fistula tract (LIFT) or less invasive ones, such as video-assisted anal fistula treatment (VAAFT), negative pressure wound therapy (NPWT), setons, fibrins and plugs, but associated with a higher risk of recurrence. An attempt to close the internal opening without jeopardising the function of the sphincter is a major advantage of those methods.³ Application of platelet-rich plasma (PRP) or porcine-derived paste (PDP) has appeared recently in the field of anal fistula therapy. PRP is an autologous product obtained from the whole blood. The value of plasma lies on its ability to soak the adjacent soft tissues relative to fistulous tract with high concentration of platelet-derived growth factors to accelerate the healing process.⁴ By contrast, PDP consists of collagen retrieved from porcine dermis, which becomes a scaffold promoting formation of a fresh granulation tissue and subsequent fistula closure.⁵ This study aimed to assess preliminary results of recurrent anal fistula treatments with PRP in comparison with PDP.

Materials and Method

Medical records of 50 patients with primary or recurrent high anal fistulas of cryptoglandular origin treated between 2017 and 2020 were retrospectively evaluated. Patients were divided into two groups: The PRP group consisted of 25 patients, including 13 (52%) male and 12 (48%) female, with median age of 32 [interquartile range (IQR): 29-39] years. The PDP group consisted of 25 patients, including14 (56%) male and 11 (44%) female, with median age of 38 (IQR: 32-41) years. Previous anal operations such as excision, fistulotomy, MAF and LIFT were performed in 19 (76%) patients from the PRP group and in 18 (72%) patients from the PDP group (Table 1). Patients underwent digital rectal examination and probing and/or dyeing of fistulous tracts under anaesthesia. High trans-sphincteric fistulas were diagnosed if more than the lower one-third of the anal sphincter was involved.² Application of either PRP or PDP was preceded with loose seton pre-treatment in all patients with purulent discharge. Then, application of bio-products was preferred for patients with a relatively long and narrow fistulous tract and with a small bore internal orifice, especially if PDP application was considered. The use of PRP or PDP depends on the surgeon and type of anal fistula. The length of the fistulous tract and the diameter of the internal opening were assessed after digital rectal examination. Curettage and cauterisation of fistulous tracts to remove the epithelium and infected granulation tissue, followed by irrigation of those canals, trimming of external orifices and simple closure of the internal orifice, were performed in all patients. The procedure was accomplished with application of PRP in the first group and PDP in the latter group. Then, 15 mL of whole blood was centrifuged just before the procedure to obtain 1 mL of PRP, using a commercial kit (Xerthra PRP Kit, Biovico, Poland). The concentrate was administered into adjacent tissues surrounding fistulous tracts, beginning from the internal orifice towards the external orifice. The penetration depth was controlled with the index inserted into the anal canal or by transrectal ultrasonography (TRUS). The procedure was repeated three times every fortnight according to the protocol until the therapeutic effect was achieved, and applications can be repeated if it was clinically justified. Then, a fistulous canal was filled with the paste Permacol (Covidien, Mansfield, MA) in one procedure. The external orifices were left open in all patients. Fistula closure was defined as the absence of discharge after gentle finger compression of an external orifice and of perianal tissues. The closure was confirmed by TRUS.⁶ Patients were evaluated in an outpatient department within 1, 6 and 12 months following final PRP or PDP application. The evaluation consisted of digital rectal examination, TRUS and completion of the Wexner questionnaire.⁷ Patients with non-cryptoglandular fistulas, e.g. Crohn’s, post-radiation and cancerous anal fistulas, were excluded from this investigation.

Statistical Analysis

Analysed data were presented as medians with range or IQR. Categorical data were presented as percentages. Differences in components of demographic characteristics among two groups were detected by Mann-Whitney U tests or chi-square test. The chi-square test was also used to examine the significance of the fistula closure rate between the groups. Changes in the Wexner score within and between groups were identified by Wilcoxon signed-rank tests or Mann-Whitney U tests, respectively. A p-value less than 0.05 was considered significant. All analyses were performed using the statistical package STATISTICA v. 13.1 (Stat Soft. Inc., Tulsa, OK, USA). The application of PRP and PDP in anal fistulas was approved by the Bioethics Committee at the University. All participants/patients signed an informed consent before this study.

Results

Complete closure of anal fistulas was achieved in 16 (64%) patients from the PRP group compared with 9 (36%) patients from the PDP group, and the difference was significant (p=0.048). The healing time ranged from 4 to 8 weeks in the PRP group with application of PRP repeated 3-5 times. Closure of anal fistulas in the PDP group occurred within 4–12 weeks. In the PRP group, anal fistula remained closed in 19 patients at the sixth month and in 16 patients at the 12^th month, but were healed in 11 and 9 patients in the PDP group, respectively. No significant difference in demographic characteristics was found between the groups, except for the higher mean age of the patients in the PRP group (p=0.010). Mild to moderate form of faecal incontinence, such as gases or liquid stools, was recognised in half of the patients from both groups before therapy and the change in the Wexner score after treatment was not significant (PRP, p=0.120; PDP, p=0.065).

Discussion

Conservative surgery is indicated for most complex and recurrent anal fistulas because of the high recurrence rates and avoidance of damage to the sphincters with subsequent faecal incontinence. Several sphincter-saving methods such as MAF, LIFT, VAAFT, NPWT, fibrins and plugs have been introduced recently.³ All these methods, except for MAF with efficacy approaching 50%, require further clinical investigation, since representative randomised trials have not yet been available.⁸ As regards LIFT, it relies on the identification of the space between the internal and external sphincters and on mobilisation and partial excision of the fistulous tract within that space. The efficacy of LIFT is below 50%.⁹ By contrast, VAAFT enables accurate debridement of fistulous tracts under sight control and closure of the internal opening. Equipment costs are major disadvantages of VAAFT. However, preliminary results of VAAFT are encouraging, with more than half of fistula closure.¹⁰ Vacuum therapy shows its potential for the management of anal fistulas. NPWT can be defined as a sphincter-saving procedure, because the anal sphincter is left intact. Moreover, it is a more effective kind of surgical drainage than use of loose setons.¹¹ With regard to fibrins, the fistulous tract is sealed with fibrin glue, starting from the external opening. A major advantage is the opportunity to repeat the procedure several times as necessary. The low efficacy of fibrins of 14%-60% is a major drawback.¹² Conversely, a plug is a bioabsorbable prosthesis made from porcine intestinal submucosa. It serves as scaffolding for host cell proliferation. As major advantage, it can be performed multiple times, but its efficacy is approximately 30% because of frequent rejections.¹³ The PDP consists of collagen type I and elastin fibres retrieved from porcine dermis. During the manufacturing process, cells are removed to reduce immunological response against foreign antigens. The collagen also undergoes cross-linking, which results in increased resistance to degradation, reduction of tissue antigenicity, higher durability and greater strength. Importantly, the paste is a slowly absorbable material, and the collagen becomes a scaffold that enables cellular infiltration and neovascularisation. The dissolution process takes on average a few months, after which the paste is replaced with patient’s dense and strong scar tissue. If compared with synthetic pastes, biological pastes induce milder inflammatory response and a more orderly collagen deposition. In addition, the cross-linked materials showed greater resistance to collagenase digestion. The major drawback is the relatively low efficacy, mainly due to frequent leakage of the paste from the fistulous tract before the occurrence of cellular infiltration and neovascularisation.^5,14

PRP is an autologous product obtained from whole blood through gradient density centrifugation. Results achieved after PRP application were better than those after PDP and other aforementioned conservative methods. The plasma not only serves as a fibrin tissue adhesive and a scaffold for cellular infiltration, but also promotes wound healing by increasing cellular proliferation, angiogenesis and collagen synthesis owing to a high concentration of platelet-derived growth factors within the soft tissues adjacent to the fistulous tracts. Mechanical compression of the fistulous tract by injecting plasma into the tissues adjacent to anal fistulas is another PRP mode of action. Finally, it carries no risk of allergies and transmitting infections, since it is an autologous product.⁴

Study Limitations

This study has several limitations, such as a retrospective study design and a small sample size. However, the study might be considered in further meta-analyses.

Conclusion

Preliminary results of local PRP application in patients with recurrent, cryptoglandular anal fistulas showed a higher rate of fistula closure than PDP treatment. However, application of either PRP or PDP might be repeated several times if recurrences occur. Both methods could be combined with other conservative, sphincter-saving methods of surgery in a selected group of patients mainly with recurrent, high cryptoglandular anal fistulas. Such methods might be recommended as novel sphincter-saving procedures for recurrent anal fistulas.

Ethics

Ethics Committee Approval: The application of platelet-rich plasma as well as of a porcine-derived acellular dermal paste in anal fistulas was approved by the Bioethics Committee at the University.

Informed Consent: All participants/patients signed an informed consent before this study.

Peer-review: Externally and internally peer reviewed.

Authorship Contributions

Surgical and Medical Practices: J.H., J.C., T.B., Concept: T.B., Design: J.H., Data Collection or Processing: J.C., Analysis or Interpretation: B.K.,  Literature Search: J.C.,  Writing: J.H.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.