Response to Letter by Spartalis et al: Platelet-Rich Fibrin in Total Laryngectomy: Further Study Concerns

We read with great interest the letter titled Platelet-rich fibrin in total laryngectomy: long-term safety concerns by Spartalis et al (Facial Plast Surg 2021. Doi: 10.1055/s-0041-1729636). The progressive transformation of normal cells into highly malignant derivatives entails the accumulation of several genetic changes. On increasing mutated cell division as a result of promotion phenomena, the risk increases for new oncogenic molecular alterations to occur, capable of inducing malignant transformation and tumor progression. Augmented mitosis in a clonal cell line triggered by a mutagenic event increases possibility of successive mutagenic events. However, this phenomenon could require more continuous doses in time than those applied in platelet-rich fibrin (PRF) therapy, taking into account that extracellular growth factors (GFs) degrade within 7 to 10 days. Then, all the GFs released are native and act on the cell membrane and not inside the nucleus; they activate cytoplasmic signaling proteins and, therefore, generate normal gene expression, unlike mutagens (e.g., smock and radiation), which are undeniably carcinogenic. Therapeutic GF-rich concentrates can sometimes act as promoters (rather than initiators) of carcinogenesis by increasing division and growth of mutant cells. Since GFs are metabolized at around 7 to 10 days, any possible carcinogenic effect would require prolonged administration than the therapy used in this study. In a review of the literature, no evidence of a relationship between the therapeutic use of PRF and cancerous transformation of normal or dysplastic tissue was found. In fact, by existing data, no definitive information about how and when PRF should be used is provided.

Pharyngocutaneous fistula is the most common complication following total laryngectomy. Incomplete excision of the tumor and coexisting complications were related to a higher chance of fistula formation. Therefore, in our study, all patients underwent primary tumor location (TL) with clinical early stage of laryngeal squamous cell carcinoma; patients with no uncontrolled systemic comorbidities also received the same treatment according to the standard operating procedure of “post-TL treatment without complications” in our hospital department. All surgeons performed the same TL-technique procedures with selective neck dissection and frozen sections from all subjects to show that the tumor had a free margin. In our study, after one and half years follow-up, no recurrent cases were found. Several literatures had stated that the rate of tumor recurrence after total laryngectomy was not associated with the manifestation of a fistula during the postoperative period.

Notwithstanding the preliminary study and limited number of patients evaluated, our results represent preliminary interesting data that need to be confirmed. Even if many applications for in situ regenerative medicine and tissue engineering have been developed, the use of platelet concentrates still proves to be controversial in existing literature. There have been no published references to the risk of infection, disease transmission, or any other undesirable effects associated with the use of PRF. On the other hand, little is known of the ideal concentrations of each GF or the optimum dosage for each concrete therapeutic situation. Furthermore, additional unidentified factors may also exist. Our current concern is to further follow up our patients because some authors had suggested that cancer risks are present due to the large quantity of GFs released by PRF administration.

Publication History

Article published online:
20 July 2021