Effect of Intra-Operative Topical 5-Fluorouracil Post-Functional Endoscopic Sinus Surgery: A Randomized Controlled Trial

Original Article Iranian Journal of Otorhinolaryngology, Vol.37(2), Serial No.139, Mar-2025 Effect of Intra-Operative Topical 5-Fluorouracil Post-Functional Endoscopic Sinus Surgery: A Randomized Controlled Trial * Lekhaa Mohanraj1, Somu Lakshmanan2, Urvashi Singh3 Abstract Introduction: Endoscopic nasal surgery has numerous potential adverse effects, adhesions are at the top of the list. 5fluorouracil (5-FU), which is an analogue of pyrimidine, is utilized in a wide variety of areas for the purpose of preventing adhesions. In the present investigation, our purpose was to analyze the impact of intra-operative application of 5-flurouracil in the nasal cavity following FESS, as well as to evaluate both subjective and objective outcomes. Materials and Methods: Following the acquisition of institutional ethical approval, a testing procedure that was randomized, prospective, and double-blinded was carried out. After the FESS, a cotton swab soaked in 1 mL of 5flurouracil at 5 mg/mL was inserted in one side of the nasal cavity and a saline-soaked one in the other. Both of these swabs were kept in place for a period of five minutes. Postoperatively, patients were assessed over 6 months duration, wherein, adhesions, discharge, crustation, edema and polypoidal changes were analyzed. Subjective symptoms such as nasal block, nasal discharge and loss of smell were also assessed. Results: At the one-week follow-up, the test group had a significantly higher incidence of adhesions (32% vs. 11.76%, respectively) (p = 0.004) than the control group. Mucosal edema, crusting, polypoidal change and nasal discharge continued to significantly diminish in both groups. Furthermore, improvement in smell perception in the test group at the 20th week post-operatively was statistically significant (p= 0.014). Conclusions: Adhesions are less common in the early postoperative period in individuals who underwent FESS with or without polypectomy when 5-FU is administered topically. There is also an improvement in smell perception with a reduction of mucosal edema, crusting, polypoidal change and nasal discharge enabling better healing. Keywords: Randomized Control Trial, Functional Endoscopic Sinus Surgery, Outcomes, 5-Fluorouracil, Adhesions, Synechia. Received date: 21 Jul 2024 Accepted date: 21 Jan 2025 *Please cite this article; Mohanraj L, Lakshmanan S, Singh U. Effect of Intra-Operative Topical 5-Fluorouracil PostFunctional Endoscopic Sinus Surgery: A Randomized Controlled Trial. Iran J Otorhinolaryngol. 2025:37(2):57-63. Doi: 10.22038/ijorl.2025.80571.3709 1Senior Registrar, ENT & Head and Neck Surgery, Madras ENT Research Foundation (MERF), RA Puram, Chennai, India. of ENT and Head and Neck Surgery,Sri Ramachandra Medical College and Research Institure, Chennai, India. 3 Department of ENT and Head and Neck Surgery, Apollo Hospitals, Chennai, India. *Corresponding Author: Senior Registrar, ENT & Head and Neck Surgery, Madras ENT Research Foundation (MERF), RA Puram, Ch 600028. E-mail – 2Department Copyright©2025 Mashhad University of Medical Sciences. This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 International License https://creativecommons.org/licenses/by-nc/4.0//deed.en 57 Mohanraj L, et al Introduction Inflammation of the nasal and paranasal sinus mucosa for at least twelve weeks is referred to as chronic rhinosinusitis (1). Three factors remain crucial for the normal physiological functioning of paranasal sinus: patency of the osteo-meatal unit (OMU), normal muco-ciliary transport and normal quality and quantity of secretions. With little tissue damage, nasal surgeries strive to cure disease, enhance nasal air flow, and enable sinus drainage by removing obstructions. Trauma to tissues can happen either directly during surgery or indirectly as a result of aberrant healing processes, including the formation of adhesions following the procedure (2). Adhesions represent one of the most frequent complications following endoscopic nasal procedures and are a reason for revision (3). As a means to reduce adhesions postsurgery, nasal splints, packing and spacers have been attempted (4-6). By blocking the enzyme thymidylate synthase, which is essential for DNA synthesis, the pyrimidine analogue 5-fluorouracil (5-FU) is able to reduce the proliferation of fibroblasts. Adhesions and difficulties connected to epithelial development can be effectively reduced using 5-FU, which is utilized by numerous medical specialties. For the treatment of actinic keratosis and psoriasis, its safety has been well-established in the fields of ophthalmology (7) and dermatology (8,9). In this study, we examined the objective and subjective outcomes of utilizing topical 5-FU on nasal cavity post-functional endoscopic sinus surgery. Materials and Methods From October 2021 through July 2023, our tertiary care teaching hospital in southern India conducted a randomized, double-blind controlled experiment (CTRI/2021/03/032286) in the department of ENT and Head and Neck Surgery. Inclusion Criteria 1. Patients of either gender who are between the ages of 18 and 65 years 2. Chronic rhinosinusitis with or without polyposis who have not responded to medication treatment 3. Lund-Mackay Scoring difference of ≤2 between both sides in CT-PNS. EXCLUSION CRITERIA 1. Revision endoscopic sinus surgery 2. A difference of 3 or more in the Lund Mackay scoring on both sides in CT-PNS. 3. Patients with uncontrolled diabetes mellitus and hypertension 4. Known allergy to 5-fluorouracil 5. Pregnancy and lactation 6. Pre-existing septal perforation or adhesion Study Design Following the use of the Two Proportion Hypothesis testing method, the sample size was 68, with 80% power and 5% alpha error. We considered 'p' values below 0.05 statistically significant. Pre-operative Evaluation A diagnosis of CRS was made based on the EPOS Criteria (10). Those enrolled in the study had no benefit from maximum medical therapy, which involved a trial of oral antibiotics and steroidal nasal sprays for 3 months. Pre operative anaesthetic evaluation was done for all patients. A written informed consent was obtained. Materials, set-up and technique General anesthesia was used for the functional endoscopic sinus surgery. Pledgets soaked with oxymetazoline (0.05%) were used for preoperative nasal packing. The surgical technique described by Messerklinger was followed for all patients. The surgery included an uncinectomy using a backbiter. The maxillary ostium was enlarged using a microdebrider. Anterior and posterior ethmoidectomy was done using a combination of instruments like curette, forceps and microdebrider. Ethmoidal bulla was removed using a curette or forceps to further expose the OMC. Ancillary procedures such as inferior turbinate submucous resection and septoplasty were performed when required. In patients with CRSwNP, sphenoidotomy and frontal sinusotomy was performed when indicated. Upon completion of surgery, (...truncated)