Local injection of platelet-rich plasma offers a new therapeutic option for the treatment of esophagotracheal fistula: a case report

Abstract

Esophagotracheal fistula (ETF), one of the most serious complications in the treatment of esophageal cancer, presents a complex management challenge. Early diagnosis and treatment are crucial to alleviate clinical symptoms and improve the quality of life of patients with ETF. The most commonly used method for treating ETF is esophageal stenting. However, because of the variable location and size of the fistula, stent placement alone sometimes fails to completely close the fistula, and complications such as fracture and displacement of the esophageal stent may occur. Therefore, safer and more effective methods for the treatment of ETF are required. In recent years, the application of bioactive factors to promote human tissue repair and wound healing has increased and achieved good therapeutic results. We herein describe a case in which we performed endoscopic injection of platelet-rich plasma directly into the ETF site and achieved a favorable outcome. This case suggests that local injection of platelet-rich plasma is a novel treatment modality for ETF.

Introduction

Esophageal cancer is a malignant tumor originating from the mucosal epithelium of the esophagus. It is characteristically invasive and associated with high morbidity and mortality rates. According to the Global Cancer Statistics 2020, esophageal cancer ranks seventh among all malignant tumors worldwide and has the fourth highest overall mortality rate. ¹ The most serious complication of esophageal cancer is the development of an esophagotracheal fistula (ETF), which has a reported occurrence rate of 5% to 10% in patients undergoing transthoracic esophagectomy. ² The incidence of ETF following chemotherapy alone is 6%. ³ The incidence of ETF following radiotherapy is 6.98%. ⁴ An ETF is an abnormal passage that forms between the esophagus and the trachea, and it has a variety of causes. Its primary clinical manifestations include dysphagia, choking, recurrent lung infections, and respiratory difficulties. ⁵ If left untreated, ETF can lead to sepsis, respiratory failure, and even death. Therefore, early detection and treatment of ETF is essential to improve patients’ prognosis and quality of life. ETF may be managed by conservative treatment, surgical treatment, or stent placement. With the continuous development of medical technology, the treatment of ETF has undergone significant advances. For example, bioactive factors have been used to promote human tissue repair and wound healing, and they have been widely applicated in the clinical setting. One notable example is the use of platelet-rich plasma (PRP) in local injection therapy, which has shown promise in the management of difficult-to-treat wounds. We herein describe a patient with ETF who was treated with endoscopic PRP injection into the fistula site.

Case report

A 70-year-old man had undergone thoracoscopic and laparoscopic resection of esophageal cancer 3 years previously. Following the operation, he underwent endoscopic esophageal balloon dilatation and esophageal stenting for recurrent episodes of food impaction. He had a medical history of hypertension and cerebral infarction. The patient was admitted to our hospital because of anterior chest discomfort and paroxysmal coughing. Upper gastrointestinal imaging revealed contrast leakage at the anastomosis to the bronchus following surgery for esophageal cancer. The passage of contrast through the anastomosis was not significantly obstructed, leading to the diagnosis of an ETF (Figure 1(a)). Subsequent gastrointestinal endoscopic examination and treatment was recommended (Figure 2(a)). The treatment plan and potential complications were discussed with the patient and his family, who provided written informed consent. The institutional review board (Hebei General Hospital Ethics Committee 2023) approved the study protocol (Approval No. 2023157). The patient provided written informed consent before voluntarily undergoing treatment. He also provided written consent for publication of this case. The reporting of this study conforms to the CARE guidelines. ⁶

Figure 1.

Comparison of upper gastrointestinal imaging results. (a) The patient underwent upper gastrointestinal imaging, which indicated the presence of postoperative esophageal cancer. Contrast leakage was observed at the anastomotic site. The contrast extended into the bronchus without significant obstruction to its passage through the anastomosis. Therefore, the possibility of an esophagotracheal fistula was considered and (b) In the postoperative review of esophageal cancer, oral iodine passed smoothly through the residual esophagus and anastomosis. Slight narrowing of the anastomosis was seen, with no leakage of contrast medium and no obvious signs of destruction.

Figure 2.

Comparison of gastroscopic findings. (a) The patient was admitted to the hospital because of esophageal stenosis and the presence of an esophagotracheal fistula. (b) The stenotic segment was dilated using a balloon, and 6 mL of platelet-rich plasma was injected around the fistula using an injection needle. (c) One month after the operation, significant improvement was observed in the fistula. Subsequently, 10 mL of platelet-rich plasma was reinjected at multiple points around the fistula using a needle and (d) Gastroscopy was conducted 3 months postoperatively, revealing no discernible fistula.

The patient underwent gastroscopy under intravenous anesthesia. The examination revealed an esophageal stenosis located 25 cm from the incisors, accompanied by a 0.8- × 0.8-mm mild depression adjacent to the stenosis in a grid-like pattern and a visible defect. The stenosis was dilated with a balloon under direct endoscopic vision, and 6 mL of PRP was injected into the submucosa around the fistula with a syringe needle. A coated metal stent of 8 cm in length and 1.8 cm in diameter was then inserted, helping the surgical procedure to be smoothly executed (Figure 2(b)). After the operation, the patient was given acid-suppressive and anti-infective symptomatic treatment, and no complications such as perforation, bleeding, or infection were observed. One month later, the patient’s choking symptoms were relieved; however, he reported an obvious foreign body sensation in the chest area. After discussion with the patient and his family, gastroscopy was performed again, and the coated metal stent was removed. The fistula was found to have significantly improved, and 10 mL of PRP was injected again at multiple points around the fistula (Figure 2(c)). Three months later, the patient reported that the discomfort in the anterior thoracic region had markedly improved and that he did not choke on liquid food. Gastroscopy showed that the fistula had healed (Figure 2(d)).

Discussion

ETF is a refractory condition that occurs when an abnormal connection is present between the esophagus and the trachea. The presence of an ETF can result in leakage of food and/or air from the esophagus into the trachea, leading to symptoms such as choking, dry cough, and dysphagia. In addition, the presence of the fistula hinders oral intake, making the patient vulnerable to weight loss and pulmonary infections. Such complications can have a significant impact on quality of life. The diagnosis of ETF relies on the patient’s medical history, clinical manifestations, and diagnostic procedures such as imaging, gastroscopy, or bronchoscopy. Gastroscopy and bronchoscopy are the primary diagnostic techniques for confirming the presence of an ETF. ⁷ Direct visualization allows the location and size of the fistula to be determined, enabling an appropriate treatment plan to be selected. PRP has shown unique advantages in promoting tissue repair and wound healing, and it has received considerable attention in clinical studies investigating its therapeutic effects on gastrointestinal fistulas. Yamaguchi et al. ⁸ demonstrated the beneficial effect of PRP treatment on intestinal anastomotic healing in rats during proximal jejunostomy. The study revealed that this effect was dose-dependent, suggesting that optimizing the concentration of PRP may further enhance the healing process of the intestinal anastomosis in rats. Hermann et al. ⁹ assessed the therapeutic effect of PRP in patients with ulcerative colitis. In their study, nine (69%) patients achieved complete closure of rectovaginal fistulas, and the fistulas remained closed for 6 to 12 months. PRP also reduces inflammation and fibrosis, alleviating pain and inflammation in the tissue surrounding the fistula. In a recent study, autologous PRP was submucosally injected around tracheobronchial fistulas under bronchoscopic guidance to achieve fistula closure. ¹⁰ PRP treatment resulted in healing of the tracheobronchial fistulas in all three patients in that study. No patients developed treatment-related complications or fistula-associated symptoms. Damien et al. ¹¹ recently conducted a study in which they administered local injections of autologous PRP to patients who developed ETF following total laryngectomy. The administration of autologous PRP resulted in complete closure of the fistula, leading to resolution of respiratory and swallowing problems. This safe, noninvasive local treatment represents a novel therapeutic approach to fistula repair.

PRP is a concentrated form of platelets extracted from autologous blood by centrifugation, and it contains three to five times the concentration of platelets found in whole blood. PRP possesses biological properties that initiate wound repair through the degradation of alpha-granules within platelets. Activation of platelets in PRP by activators such as thrombin and calcium chloride leads to the release of numerous growth factors from the alpha-granules, including platelet-derived growth factor, epidermal growth factor, transforming growth factor, vascular endothelial growth factor, and others. Platelet-derived growth factor stimulates cell proliferation, cell differentiation, and collagen synthesis. Vascular endothelial growth factor promotes vascular endothelial cell proliferation and capillary formation. Fibroblast growth factor stimulates new cell growth and tissue repair. Epidermal growth factor facilitates wound healing and angiogenesis. Transforming growth factor, which is abundant in various tissues and cells, promotes tissue regeneration and plays a crucial role in wound healing. These properties serve as the foundation for the use of PRP in wound treatment.

In this case report, PRP was injected directly into the fistula site. The growth factors and cytokines present in PRP promote tissue healing and repair at the fistula site. They also reduce the size of the fistula hole, accelerate fistula closure, and exert anti-infective and anti-inflammatory effects. In addition, local injections offer targeted therapy, minimizing systemic exposure and avoiding potential complications. This nonsurgical approach presents a promising treatment option for high-risk patients who are ineligible for surgical intervention, avoiding the side effects and risks associated with traditional surgery. However, efficacy may vary on a case-by-case basis, and specific treatment outcomes should be assessed individually for each patient. Despite the successful application of PRP in treating chronic non-healing wounds, there is a lack of evidence from large-scale in vitro animal cell models and multicenter randomized controlled clinical studies. Therefore, further research is needed to determine how biotechnological methods such as PRP can be effectively used to treat chronic non-healing wounds based on the patient’s condition.

Conclusions

This case report highlights the potential benefits of PRP injections as a therapeutic approach for ETF. However, further research involving a larger cohort of patients is needed to confirm these findings.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231220874 - Supplemental material for Local injection of platelet-rich plasma offers a new therapeutic option for the treatment of esophagotracheal fistula: a case report

Supplemental material, sj-pdf-1-imr-10.1177_03000605231220874 for Local injection of platelet-rich plasma offers a new therapeutic option for the treatment of esophagotracheal fistula: a case report by Jing Han, Lihui Yue, Weizhuang Jia, JunLong Li, Yan Liu and Xichun Zhu in Journal of International Medical Research