Bradykinin Receptor B1 and C-Reactive Protein as Prognostic Factors for Pharyngocutaneous Fistula Development After Laryngectomy

Abstract

Pharyngocutaneous fistulae (PCF) are one of the most common complications after laryngectomy. Predisposing risk factors have been studied, yet knowledge to determine which patients are prone to developing a fistula remains scarce. This study aims to establish prognostic parameters to identify individual patients at risk for PCF development. As PCF and inflammation seem to be interwoven, this work focuses on markers able to detect an inflammatory response. We retrospectively analyzed all patients who had undergone a laryngectomy at our clinic in the years 2007 to 2017 (n = 182). Immunohistochemical expression of bradykinin type 1 and 2 receptor and vascular endothelial growth factor receptor 2 was studied in all available tumor samples. Additionally, the clinical inflammation parameters 'body temperature', 'pain', 'c-reactive protein (CRP)', and 'leucocytes' were postoperatively tracked in all patients. The times between fistula diagnosis, therapeutic approach, and hospital discharge were recorded. We found a strong correlation between inflammation and the formation of a fistula. High bradykinin 1 receptor expression in the tumor samples correlated with postoperative PCF development. Persistently elevated CRP and leukocyte levels beyond the 6th postoperative day were also risk factors. A decreased time lapse between PCF diagnosis and surgical revision clearly correlated with a shorter hospital stay. In this study, we identified a bradykinin 1 receptor positive patient group at high risk for development of PCF. We recommend close monitoring for fistula formation in these patients to ensure timely intervention.

Inflammation‐Based Score (Combination of Platelet Count and Neutrophil‐to‐Lymphocyte Ratio) Predicts Pharyngocutaneous Fistula After Total Laryngectomy

“…One study reported that, the application of platelet‐rich fibrin (PRF) in suture repair of the pharynx reduces the incidence of PCF; PRF influences the expression of various cytokines and growth factors 32 . Another report revealed that the expression of bradykinin 1 receptor, which plays an important role in the inflammatory response, is a risk factor for PCF 33 …”

“…32 Another report revealed that the expression of bradykinin 1 receptor, which plays an important role in the inflammatory response, is a risk factor for PCF. 33 In a study by Aires et al involving 157 patients with squamous cell carcinoma of the larynx, patients with NLR >2.5, exhibited a higher risk of developing PCF after total laryngectomy. 9 Our results corroborate this finding.…”

Using post‐operative trend in C‐reactive protein to predict fistula in neopharyngeal repairs following laryngectomy and pharyngectomy surgery in fifty‐five patients

“…Koob et al 2 recently reported that persistently elevated CRP beyond post‐operative day six was a risk factor for fistula formation after laryngectomy. However, there are limited data relating to CRP in head and neck surgery.…”

“…Pharyngocutaneous fistula is a major post‐operative complication; one recent meta‐analysis reported the incidence at 21% 1 . Uncontrolled salivary leakage through the fistula results in infection, impaired wound healing, risk of saliva‐induced erosion of a major vessel, increased cost of treatment and has a negative effect on the patient's physical and psychological well‐being 2 . Studies have identified risk factors for fistula formation 1,3 but there is less research to identify those patients at risk of fistula formation, specifically for laryngectomy‐related neopharyngeal repairs.…”

Surgical emphysema as an early sign for pharyngocutaneous fistula following total laryngectomy: a case report

“…The relevance of wound amylase concentration for early detection of PCF has been shown in many studies [10]. Koob and his colleagues described the role of Bradykinin Receptor B1 and C-reactive protein as prognostic factors for pharyngocutaneous fistula development after laryngectomy [11].…”