Platelet-rich Plasma Injection for Enterocutaneous Fistula: A Case Report

An ECF is an abnormal communication between the small or large bowel and the skin. It can lead to prolonged hospitalization, pain, discomfort, additional surgery, and serious psychological problems.¹ Most ECFs occur secondary to surgical complications, and postoperative fistulas account for 75% to 85% of all intestinal fistulas.² Management of ECF is difficult and requires multidisciplinary care, including that of gastroenterologists, surgeons, wound care specialists, and dietitians. Conventional treatments include the use of growth inhibitors (eg, octreotide) to reduce fistula output as well as closure of fistulas with materials such as fibrin glue and 3-dimensional printed fistula stents.³ For most postoperative ECFs, further surgery is planned only if satisfactory results are not achieved with nonsurgical treatment.⁴

PRP is a blood product rich in platelets made from a patient’s own blood by centrifugation. The healing properties of PRP are well documented. Platelets contain 3 types of granules—α, δ, and lysosomes—of which α granules are the most unique and most abundant type and contain the bulk of the platelet secretome.⁵

After PRP is activated, α granules begin to release a large number of growth factors and cytokines within 10 minutes, such as vascular endothelial growth factor, tumor growth factor β, platelet-derived growth factor, and endothelial growth factor.⁶ These factors act synergistically to promote angiogenesis, fibroplasia, and epithelial re-formation.^7,8

Compared with standard of care, PRP can both seal the fistula to reduce fistula output and release a large number of growth factors and anti-inflammatory factors, thus providing a suitable environment for cell proliferation and migration. In addition, PRP is an autologous agent, which eliminates concerns about disease transmission or immunogenic reactions.⁹ Thus, in a patient with a low-output ECF and without sepsis, PRP may be superior to standard of care. In the case reported herein, fistula repair was achieved after a single injection of PRP.

A 52-year-old male with a history of duodenal perforation and duodenal fistula repair surgery was hospitalized owing to long-term leakage at the drain site, which had not closed by 7 months after drain removal. The effluent volume was 10 mL per 24 hours (Figure 1A). The patient provided permission to publish the case details and associated images.

The patient reported that after the drainage tube was removed he performed regular dressing changes at the wound site, but the wound did not heal and repeated ulceration occurred. Since the onset of the disease, the patient had not experienced significant abdominal pain or fever postoperatively. The physical examination findings on presentation to the authors were as follows: height, 175 cm; weight, 80 kg; and BMI, 26.1 kg/m². A nonhealing wound with a diameter of approximately 0.5 cm was observed in the left upper abdomen.

There was a small amount of light-yellow fluid exuding from the wound, and there was no obvious redness or swelling around the wound. Laboratory test results were as follows: white blood cell count, 5.3 × 10⁹/L; red blood cell count, 5.28 × 10¹²/L; hemoglobin level, 155 g/L; platelet count, 287 × 10⁹/L; C-reactive protein level, 2 mg/L; blood glucose level, 7.36 mmol/L; and albumin, 50.6 g/L. The authors of the present report suspected that the wound on the skin surface of the abdominal wall may have been connected to the intestinal cavity.

Whether or not the sinus was connected to the intestinal cavity could not be determined based on computed tomography of the abdomen; however, angiography of the sinus confirmed the authors’ suspicion. The diagnosis of ECF was made based on contrast radiologic examination findings (Figure 1B, 1C). Because of the lack of evidence of sepsis in this patient and the low-output ECF, the authors believe the lack of growth factors resulted in long-term nonhealing of the drain site. In this setting, traditional methods such as octreotide and negative pressure wound therapy may not achieve the desired effect because these treatments cannot provide the necessary growth factors to the site.

The PRP was made with a sample of 50 mL of autologous blood. The PRP and thrombin were injected into the fistula through an injection device containing a union tee. The tube extending from the injection device was inserted into the fistula, after which PRP and thrombin were injected as the tube was retracted outward so that the PRP was instantly activated into gel that remained in the fistula to promote wound healing (Figure 2A).

One week after treatment, minimal secretion of the fistula was observed. The fistula closed within 2 weeks following treatment with PRP (Figure 2B). At 6-month follow-up, the patient no longer felt abdominal distension and abdominal pain, and no complications had been reported.

Despite advances in antibiotics and surgical techniques, the management of ECF remains extremely challenging. The principles of ECF treatment are well defined and generally accepted. Initial treatment includes fluid resuscitation and electrolyte rebalancing, control of sepsis with antibiotics, and drainage of infected pus when necessary. Subsequent treatment steps include nutritional support, control of fistula output, and treatment of the skin around the fistula.¹ The goal of treatment is to close the fistula with minimal morbidity and mortality. More effective treatments are needed to hasten fistula healing and reduce the number of reoperations required.

The most common cause of chronic wounds (ie, wounds of ≥3 months’ duration) is abnormal growth factors. Conventional therapies, such as dressings and surgical debridement, do not provide satisfactory healing because they cannot provide the necessary growth factors to regulate the healing process. Creating a suitable growth environment for the wound is the key to healing a chronic wound.

The use of PRP for the topical treatment of chronic wounds is based on the understanding that the concentration of growth factors in chronic wounds is low.⁹ The application of PRP to ECF is based on the same principle. Natural healing without the use of additional growth factors is relatively difficult. PRP is well suited as a novel and harmless topical treatment for chronic cavity wounds with inadequate blood supply.¹⁰ Additionally, the anti-inflammatory properties of leukocytes in PRP have antimicrobial effects on wound healing and may promote fistula closure.¹¹

At the time of this writing, no studies reporting the results of PRP treatment for ECF had been published; however, some studies have reported promising results concerning the efficacy of PRP in the management of many fistulas. One study reported successful healing after treatment with PRP in a patient with a fistula following bursitis of the lateral malleolus; prior efforts to manage the fistula with conventional wound therapy had been unsuccessful.¹² In a different study, PRP was injected into the submucosa around a tracheobronchial fistula to close the fistula.¹³ Other studies have confirmed the effectiveness of PRP in the treatment of anal and rectovaginal fistulas.^14-16 The application of PRP in the management of long-term nonhealing ECF provides sufficient growth factors to accelerate healing and sealing of the fistula. In the case reported in this study, the use of PRP in the treatment of ECF had positive results and led to closure of the fistula.

This case report has limitations, one of which is that it involves only one patient treated at a single institution. More rigorous and systematic studies will help to evaluate the therapeutic effect of PRP on postoperative ECF, so as to help surgeons better solve the problem of postoperative ECF nonunion. In addition, because PRP requires the collection of the patient’s own blood, there are certain contraindications, such as thrombocytopenia or platelet dysfunction. This will result in a small number of patients being unable to undergo PRP treatment. The authors suggest that guidelines should be revisited after larger and more thorough investigations are carried out, provided larger studies confirm the efficacy of PRP in the management of ECF.

As shown in this case, PRP may be an appropriate treatment option for patients with ECF with no signs and symptoms of generalized sepsis or peritonitis to promote fistula closure and to decrease time to healing. This treatment can reduce the patient’s pain and can be a reliable option for surgeons before performing surgical treatment. The authors of this case report recommend application of PRP in the management of nonhealing fistulas.