Treatment of recalcitrant esophagocutaneous fistula by platelet-rich-plasma-fibrin glue: A case study

Abstract

Introduction

Recalcitrant esophagocutaneous fistula is a very uncommon complication after neck surgery. Management of this non-healing fistula has long been a topic of debate. This report provides an approach for treating it.

Presentation of case

A 65-year-old woman presented nineteen years after branchial cleft cyst surgery with cyst recurrence associated with swelling. Sonography displayed a collection in the front of the left carotid artery in the suprasternal notch. On the CT, a similar finding was seen, a collection with gaseous density in front of the left sternocleidomastoid and a hypodense nodule on the right lobe of the thyroid. The pathology report describes an abscess with many macrophages and neutrophils, fat necrosis, microcalcification, and foreign body reaction around amorphous bodies. Again, surgical resection of the swelling area and tract was done and an esophago-cutaneous fistula was developed after surgery which did not heal after 6 months.

Clinical discussion

According to accelerating the healing time and complete closure of chronic wounds such as lower-extremity diabetic ulcers, persistent pneumothorax, anal fistula, and recalcitrant gastrocutaneous fistula by using platelet-rich plasma (PRP) and fibrin glue (FG); PRP-FG can be considered as a safe and effective treatment option for chronic wound healing. So, for treatment of this fistula, PRP-FG was used. PRP-FG was obtained from the patient's blood and injected into the fistula tract. The discharge was stopped after one week and the fistula was cured.

Conclusion

PRP-FG injection into the fistula tract provides a simple and non-invasive approach for the treatment of recalcitrant esophagocutaneous fistula.

Highlights

• •Treatment of recalcitrant esophagocutaneous fistula is controversial.
• •Platelet-rich plasma (PRP) and fibrin glue (FG) can used to manage the fistula.
• •In this case, the fistula healed well by using autologous PRP-FG injection.

1. Introduction

The formation of esophagocutaneous fistula is an unusual event. Common reasons for fistula formation are low-grade infection, esophageal injury during operation or after trauma, pressure necrosis, loose implants, and bone graft. Neck/throat pain, dysphagia, fever, and subcutaneous emphysema are the most frequent clinical symptoms. Usually, spontaneous closure is achievable following antibiotic therapy and parenteral nutrition, however, in some cases, the fistula cannot be healed [1].

Branchial cleft cysts account for almost 20 % of pediatric neck masses [2]. They usually appear at the end of childhood or adolescence when a previously unknown cyst gets infected. Only a very small percentage may present for the first time in adulthood [3]. The cysts are approximately constant in their position in the neck, anterior to the sternocleidomastoid muscle [4].

Branchial cleft cysts are further subdivided based on developmental origin [5]. A fistula tract to the skin will be formed following recurrent infections of branchial cysts. Recurring infections can make surgical removal difficult and increase the danger of damage to major structures like the facial nerve when the parotid gland is engaged [6]. Severe acute infections of the third or fourth branchial cleft cysts can lead to pharyngeal edema resulting in swallowing issues and obstruction of the respiratory tract. Management of branchial cleft cysts starts with the control of the infection if present. The mass is usually removed after the infection is eliminated to avoid further issues [7]. In rare cases, a persistent esophagocutaneous fistula may be developed. We report a case of recalcitrant fistula following surgery of recurrent branchial cleft cyst, where autologous platelet-rich plasma (PRP) and fibrin glue (FG) have been applied for treatment. Our work has been reported in line with the SCARE criteria [8].

2. Case presentation

A 65-year-old female, a known case of Sjögren's syndrome of 20 years ago, had a cystic neck mass which had been expanded every time with a common cold. Cyst, fibrotic tissue, and its tract followed to supratonsillar area were resected surgically. On the pathology report, the branchial cleft cyst was confirmed. Nineteen years after surgery, she returned with the recurrence of the cyst presented by swelling in the supraclavicular area on the thyroid zone. Sonography displayed a collection in the front of the left carotid artery in the suprasternal notch. On the CT, a similar finding was reported, a collection with gaseous density in front of the left sternocleidomastoid and a hypodense nodule on the right lobe of the thyroid. Endoscopy did not reveal any defect in the oropharynx or nasopharynx. The pathology report describes an abscess with many macrophages and neutrophils, fat necrosis, microcalcification, and foreign body reaction around amorphous bodies like part of food, or remaining suture. Again, a surgical resection of the swelling area and tract was done. An esophago-cutaneous fistula was developed after surgery which did not heal after 6 months. The surgeon and patient did not want to do surgery again (Fig. 1. A: patient drinks milk before treatment). Based on our institutional experiences, autologous PRP-FG protocol was recommended.

Fig. 1.

The serial photography of the treatment of the patient. (A) Esophago-cutaneous fistula before the treatment by PRP-Fibrin Glue, (B) Improvement of esophagocutaneous fistula after treatment.

3. PRP and FG preparation and application

Autologous PRP-FG preparation was prepared according to our previous method in four steps [9]: 1) sixty cc peripheral blood was taken in nine cc clinical grade citrate buffer. 2) four cc PRP was obtained by first centrifugation at 2000 ×g for two min and then second centrifugation at 4000 ×g for eight min and the supernatant plasma was transferred to another sterile tube and left four cc PRP. 3) The fibrinogen was prepared from plasma related to step 2. After freezing at −70 °C and thawing at 4 °C, the plasma was centrifuged at 6500 ×g for five min. The precipitated fibrinogen was separated from the supernatant plasma and left four cc. 4) Thrombin preparation: 10 % calcium gluconate was added to ten cc separated plasma from step 3. The clot was created after thirty min, it was shaken quickly and centrifuged at 3500 ×g for three min and one cc supernatant plasma was transferred to another sterile tube that contained thrombin. Four cc of PRP, four cc FG and one cc thrombin were mixed and injected into the fistula tract through the external orifice, and the patient was discharged 4 h after PRP-FG application from the hospital.

There were no complications during and after the injection. The discharge of the fistula was stopped after one week and patiently considered herself clinically cured. After 4 months of follow-up, the patient was completely satisfied and happy (Fig. 1. B: patient drinks milk after treatment).

4. Discussion

This case study shows that autologous PRP-FG can cure a recalcitrant esophagocutaneous fistula safely which developed after surgery for branchial cleft cysts. The outstanding repair of the fistula is related to the application of the main contributor components in regenerative tissue such as platelets and FG together.

Optimal fistula healing requires the well-coordinated processes of proliferation, cell migration, remodeling, and extracellular matrix deposition which platelet growth factors and FG scaffold are instrumental in triggering and sustaining these events [10].

PRP gives optimal local concentrations of regenerative growth factors for fistula treatment. In platelets, growth factors are found in α-granules and dense granules. The α-granules contain these factors: TGF-β, PDGF, IGF, FGF, EGF, VEGF, and ECGF; which take part in cell differentiation, cell proliferation, chemotaxis, and angiogenesis.

Dense granules contain serotonin, histamine, calcium, dopamine, and adenosine. Serotonin and histamine by increasing the capillary permeability, allow the inflammatory cells to penetrate the fistula and stimulate macrophages. Thus, bioactive factors play an important role in the regenerative process by regulating cell recruitment, cell replication, and cell differentiation [11,12]. PRP has the best performance when the blood platelet level is 4 to 5 times higher than the initial level. Lower concentrations may not improve healing and higher concentrations may not increase healing. Feng et al. reported that “PRP has antibacterial activity against Candida albicans, Cryptococcus neoformans, Escherichia coli, and Staphylococcus aureus” [13].

FG is a local biological sealant in which thrombin cleaves the fibrinopeptide A and B monomers from the fibrinogen chain, which polymerize to form a robust fibrin clot ten times stronger than a physiological clot at the site of application. This clot produces a crucial temporary extracellular matrix and is actively used by cells to initiate fibrin-mediated responses for instance cell adhesion, proliferation, and migration [14].

Fibrin clots promote fistula repair by forming a provisional matrix and provoking local fibroblast proliferation and collagen synthesis, which are then replaced by connective tissue and new blood vessels. Fibrin clot halts fibrosis [15]. FG has two important functions: 1) delivery of growth factors to promote fistula repair; and 2) creating a temporary robust scaffold [16].

In the present case report, the application of autologous FG provided additional value in reducing cost and avoiding the transfer of any blood-borne diseases.

5. Conclusion

A case is presented where autologous PRP-FG injection into the fistula tract offered a simple, and non-invasive procedure for healing of recalcitrant fistula which was developed after surgery. This case offers further evidence in order to support the efficacy of autologous PRP-FG treatment in recalcitrant wound and fistula healing and also underlines the necessity for larger double-blind, multi-center studies.

Consent

Written consent for the publication of this case report and its accompanying images has been acquired from the patient. No information in the submitted manuscript can be used to identify the patient.

Declaration of informed consent

Written consent for the publication of this case report and its accompanying images has been acquired from the patient. No information in the submitted manuscript can be used to identify the patient.

Ethical approval

Ethical clearance is not required for this case report, according to our institution's research ethics committee. The committee has verified that the report adheres to standard clinical practices and does not involve experimental interventions or the need for additional data collection.

Funding

The author(s) received NO financial support for the preparation, research, authorship, and/or publication of this manuscript.

Author contribution

All authors contributed to the conceptualization, data collection, and manuscript writing. All authors have read and approved the final aspects of this manuscript.

Guarantor

Daryoush Hamidi Alamdari.

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Conflict of interest statement

None.