Topical Application Of MMC Research Articles

Effect of topical application of mitomycin-c as an adjuvant treatment of laryngotracheal stenosis

Background Laryngotracheal stenosis (LTS) has become more frequent because of prolonged endotracheal intubation (PEI). The endoscopic treatment of LTS is often associated with high recurrence rate owing to excessive fibrosis. Mitomycin-c (MMC) inhibits fibroblast proliferation, so it is used at the time of endoscopic dilation to improve outcomes. Objective The aim was to assess the effect of application of topical MMC in the treatment of LTS to prevent recurrence of stenosis. Patients and methods A prospective study was carried out on 20 patients with LTS subjected to endoscopic dilatation. All patients were divided to two groups: group A (case group) included 10 patients with LTS who were subjected to endoscopic dilatation with topical application of MMC (0.5 mg/ml), and group B (control group) included 10 patients with LTS who were subjected to endoscopic dilatation without topical application of MMC. A neck computed tomography scan was done for all patients to detect the site and length of stenotic area. Results In group A, LTS was due to PEI in six (30%) patients, due to laryngoscleroma in three (30%) patients, and due to Wegener’s granulomatosis in one (10%) patients, whereas in group B, it was due to PEI in four (40%) patients, due to rhinoscleroma in four (40%) patients, and due to Wegener’s granulomatosis in two (2%) patients. The most common site of stenosis was subglottic and trachea in both groups. Most of the patients in case group ended up with grade 2 dyspnea (mild dyspnea with no limitation to daily activities), whereas three patients in control group achieved this outcome, with a statistically significant difference (P=0.043). None of the patients in the case group developed postoperative stridor 6 months after surgery, compared with four patients in the control group. Conclusion Topical application of MMC as an adjuvant treatment for endoscopic management of LTS has shown good results, low recurrence rate, and high success rate.

Comparative evaluation of decellularized bovine omentum alone and in combination with mitomycin-C in the management of corneal injuries in dogs.

Background and Aim:Ulcerative corneal lesions are common ocular affections encountered in veterinary ophthalmology, having a higher incidence in dogs with brachycephalic conformation. Prompt and effective diagnosis and repair are necessary to avoid corneal perforation and restore vision. Corneal wound healing is a complex phenomenon often resulting in vision impairment as a consequence of corneal fibrosis and pigmentation. The present study investigated the efficacy of decellularized and gamma-irradiated bovine omentum as an extracellular matrix scaffold in the reconstruction of extensive and full-thickness corneal defects, and the cytotoxic effects of mitomycin-C (MMC) to prevent corneal fibrosis and pigmentation.Materials and Methods:Twelve injured corneas of eleven dogs irrespective of breed, age, and sex were randomly divided into Groups I and II, consisting of six corneas each. Under general anesthesia, corneal grafting with decellularized and gamma-irradiated bovine omentum was carried out in Group I, whereas Group II corneas underwent single time intra-operative application of topical MMC for 2 min before corneal grafting with the same material. Epithelialization of cornea and observations including corneal edema, neovascularization, the extent of pigmentation, corneal clarity, and scarring was recorded on days 7, 14, 21, and 60 postoperatively.Results:All corneas in Group I showed early epithelialization by day 7 compared to Group II where the MMC delayed epithelialization in 50% of the corneas. Visual function scores improved greatly from 0.17±0.17 in Group II on the day of presentation to 1.0±00 by the end of the observation period compared to Group I (from 0.33±0.15 to 0.88±0.11). Although epithelialization and corneal healing were delayed, 50% of the corneas recovered with undetectable corneal scar and melanosis at the end of the observation period in Group II due to the anti-fibrotic effect of MMC.Conclusion:From the present study, it was concluded that re-epithelialization of the cornea was enhanced by corneal grafting with decellularized bovine omentum, and application of MMC was effective in delaying corneal fibrosis and pigmentation.

A randomized controlled trial of adjuvant mitomycin-c in endoscopic surgery for laryngotracheal stenosis.

Topical mitomycin-C (MMC) application is a commonly accepted adjuvant therapy in the surgical treatment for laryngotracheal stenosis (LTS). However, the efficacy of MMC has not been examined in a prospective, randomized clinical trial in humans. We aimed to examine the efficacy of MMC in the treatment of LTS patients as compared to a placebo-controlled group. Prospective, randomized, double-blind, placebo-controlled clinical trial. Fifteen patients with LTS were enrolled in a 24-month trial and randomized into one of two groups: 1) endoscopic surgical treatment with topical application of MMC or 2) endoscopic surgical treatment with topical application of saline. Postoperatively, patients were evaluated at standardized intervals with a symptom questionnaire and spirometry. Subsequent surgery was performed as needed based on relapse of stenosis on exam and patient-reported symptom severity. The average interval between surgical treatments was 17.9 months in the placebo group and 17.4 months in the MMC group (P = .95). There was no difference in magnitude of peak inspiratory flow (PIF) improvement between groups. The average magnitude of PIF change was 1.3 L/sec and 1.1 L/sec for the placebo and MMC groups, respectively (P = .64). Similarly, there was no difference in magnitude of symptom improvement or duration of symptom improvement between the two groups. This prospective, randomized. double-blind. placebo-controlled trial suggests that the use of MMC as a topical adjuvant therapy has no additional benefit in the endoscopic surgical management of LTS. Further study is needed. 1b Laryngoscope, 130:706-711, 2020.

Role of Topical Mytomycin C Application in Improving Outcome of Functional Endoscopic Sinus Surgery

Background: functional endoscopic sinus surgery, (FESS), is a minimally invasive surgical procedure that opens up the paranasal sinus ostia with an endoscope. Endoscopic sinus surgery is seen as the standard treatment in chronic rhinosinusitis and Sinonasal polyposis. Objective: it was to assess the efficacy of intra and postoperative topical application of Mitomycin C after endoscopic sinus surgery in reducing adhesions and scar formation and improving outcome of FESS. Patients and Methods: this study included 60 cases (24 female (40%) and 36 male (60%) ranging in age from 18 to 50 years) with mean 34 bilateral chronic rhinosinusitis with or without sinonasal polyposis undergoing functional endoscopic sinus surgery. Every patient in this study had been submitted for full history taking, general examination, full ENT examination routine preoperative laboratory investigations and computerized tomography study on the nose and paranasal sinuses. Functional endoscopic sinus surgery had been done for all patients. Results: In our study, bilateral nasal obstruction was presented in 46 patients (76.6%), anterior nasal discharge was presented in 22 patients (36.6%), posterior nasal discharge was presented in 18 patients (30%), headache was presented in 40 patients (66.6%) and facial pain was presented in 12 patients (20%). Endoscopic assessment of the patients 2 months after F.E.S.S revealed that the adhesions presented in 32 sides (26.7%) mainly occurred on the control side 25 (41.7%) while the Mitomycin C side showed minimal adhesions 7 (11.7%) with significant P value (0.04). Conclusion: Topical application of MMC at end of FESS has beneficial role in prevention of adhesion formation and synechiae without any side effects/complications.

Systemic Absorption of Mitomycin-C When Used in Pterygium Surgery.

To determine whether scleral topical application of mitomycin-C (MMC) results in measurable plasma levels of systemic absorption. The study comprised 27 patients who were treated with MMC 0.2 mg/mL (0.02%) for 60 seconds during pterygium surgery. Blood samples were taken 30 minutes after surgery and evaluated by the human plasma liquid chromatography tandem-mass spectrometry method to determine the presence of MMC. The amount of MMC in 27 samples tested was determined as below 0.25 ppb (ng/mL). In this study of 27 patients treated with topical application of MMC for pterygium surgery, there was no measurable evidence of systemic drug absorption. Although systemic absorption has been found with the use of larger quantities of MMC, there is an extremely low likelihood of systemic absorption or toxicity of MMC after pterygium surgery.

Systemic absorption of mitomycin-C when used in refractive surgery

To determine whether corneal topical application of mitomycin-C (MMC) results in measurable plasma levels of systemic absorption. Madigan Army Medical Center, Refractive Surgery Center, Fort Lewis, Washington, and Micro-Constants Laboratory, San Diego, California, USA. Case-control study. The study comprised male and female active-duty soldiers having excimer laser photorefractive keratectomy with MMC. Patients who met inclusion criteria were asked to provide a blood sample immediately after being treated with MMC 0.2 mg/mL (0.02%) for 30 seconds. Human plasma samples were evaluated by liquid chromatography mass spectrometry to determine whether MMC was present. Thirty samples were submitted for evaluation. There was zero detection of MMC in the submitted samples. The quantifiable limit was greater than 10.0 ng/mL. All samples were below this. In this study of 30 patients with topical application of MMC for refractive surgery, there was no measurable evidence of systemic absorption. Although systemic absorption has been found with use in larger quantities, it was not known whether MMC toxicity concerns could be extrapolated to the refractive surgery population. This information allows counseling of patients on the extremely low likelihood of systemic absorption or toxicity following current techniques for refractive surgery. No author has a financial or proprietary interest in any material or method mentioned.

Effect of topical application of mitomycin-C on wound healing in a postlaminectomy rat model: An experimental study

The aim of this study was to investigate the effects of topical application mitomycin-C (MMC) on wound healing after laminectomy. 60 adult male SD rats were equally and randomly divided into five groups. Laminectomy was performed at the level of L1 in all rats. After hemostasis was achieved, cotton pads soaked with saline and MMC (0.1mg/ml, 0.3mg/ml, 0.5mg/ml and 0.7mg/ml) were directly subjected to the exposed dura for 5min in each group. Two weeks after laminectomy all the rats were killed. The vertebral column including the back scar tissue and muscles was obtained to make paraffin sections. The hematoxylin–eosin staining and Masson staining were performed with the obtained paraffin sections. The number of the fibroblast and the capillary density were counted by the hematoxylin–eosin staining slice. The extent of epidural fibrosis and the expression of vascular endothelial growth factor (VEGF) were evaluated by the immunohistochemical slice through a computer image analysis system. Our data showed that the number of fibroblast, capillary density and fibrotic tissue in the 0.5 and 0.7mg/ml MMC groups was significantly lower than the control, 0.1 and 0.3mg/ml MMC groups; while the expression of VEGF in control and 0.1mg/ml MMC groups was notably higher than 0.3, 0.5 and 0.7mg/ml MMC groups. Topical application of MMC above the concentration of 0.3mg/ml could affect all steps of the wound healing process via inhibiting the angiogenesis and fibroblast proliferation, thus delayed the wound healing after laminectomy.

Photorefractive Keratectomy With Mitomycin-C for Consecutive Hyperopia After Radial Keratotomy

To evaluate the safety, efficacy, and stability of excimer laser photorefractive keratectomy (PRK) and mitomycin-C (MMC) 0.02% for consecutive hyperopia after radial keratotomy (RK). A prospective, nonrandomized, noncomparative interventional case series of 35 eyes (22 patients) with consecutive hyperopia after RK. All eyes were treated with PRK, using a single intraoperative topical application of MMC 0.02% for 60 seconds. Uncorrected visual acuity, best spectacle-corrected visual acuity, refraction, slit-lamp evidence of corneal haze, and endothelial cell counts were evaluated for up to 18 months after surgery. Postoperative follow-up was 9.6 +/- 5.5 months (ranged from 3 to 18 months). The mean spherical equivalent was +3.36 +/- 1.94 diopters preoperatively and +0.27 +/- 1.38 diopters 12 months after surgery. The uncorrected visual acuity was > or =20/30 in 37.1% of the eyes at 1 month and 78.6% of the eyes at 12 months. At 12 months, 14% of the eyes lost up to 1 line of Snellen acuity in the best spectacle-corrected visual acuity. No corneal haze was observed and the endothelial cell counts remained unchanged postoperatively (P > 0.05). PRK with MMC 0.02% for consecutive hyperopia after RK seems to be a safe and effective procedure at least in the short-term period of 6 months.

Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: Are two applications better than one?

Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short-term improvement, is often associated with long-term relapse. Mitomycin-C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3-6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application. A randomized, prospective, double-blind, placebo-controlled clinical trial. Twenty-six patients with laryngotracheal stenosis due to idiopathic subglottic stenosis, postintubation stenosis, or Wegener's granulomatosis entered a protocol to receive three endoscopic CO(2) laser and dilation procedures over a 3-month interval. At the first procedure, after radial CO(2) laser incision and airway dilation, all patients received topical application of MMC (0.5 mg/mL) to the airway lesion. One month later, a second endoscopic incision and dilation was performed and the patients were randomized to either a second application of mitomycin-C or to application of saline placebo. A third dilation procedure was performed 2 months later, without MMC application. Patients were followed for up to 5 years for relapse of airway stenosis with clinical symptoms sufficient to require a subsequent procedure. The relapse rates at 1, 3, and 5 years were 7%, 36%, and 69% for patients treated with two applications of MMC compared to 33%, 58%, and 70% for patients treated with one application of MMC. The median interval to relapse was 3.8 years in the two-application group, compared with 2.4 years in the one-application group. This prospective randomized double-blind placebo-controlled trial suggests that, in the endoscopic management of laryngotracheal stenosis, two applications of MMC given 3-4 weeks apart after airway radial incision and dilation reduces the restenosis rate for 2 to 3 years after treatment when compared to a single application. However, restenosis and delayed symptom recurrence continues so that at 5 years the relapse rates are the same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic stenosis in the majority of patients.

Resultados de la aplicación de mitomicina en la dacriocistorrinostomía endonasal y endocanalicular con láser diodo

Aim of the studyTo study the effects, secondary effects and security of the intrasurgical application of mitomicyn C during endonasal and endocanalicular dacryocystorhinostomy with diode laser (TLA-ELA DCR). MethodsWe carried out a randomized, prospective, interventional and double blind study in 200 patients: intrasurgical mitomicyn C was applied in 150 of then (0.4 mgr/0.2 ml) for 5 minutes by means of a polivinil acetate dressing over the osteotomy. In other 50 patients MMC was not used we followed up at 24 hours, 10 days and 1, 3 and 6 months after surgery. Endoscopic aspects and possible complications were valued. The results were compared using the Chi-squared test with the Yates correction. We looked for the presence or abscense of secondary effects in the application of mitomicyn C. ResultsThe average follow up was 15.25 months (range 6 to 21 months). The percentages of alterations for excesive scarring were 21.77% in patients without and MAC 8.03% in the ones MMC. The difference was statisticaly significant (p= 0.02). We did not find secondary effects due to application of mitomcyn. ConclusionsIntrasurgical application of topical MMC during TLA-ENL DCR reduces the number of pathological findings due to scarring of the surrouding area of the new drainage without secondary effects.

Increased expression of epidermal growth factor receptors in the tracheal epithelia after topical mitomycin-C in rabbits

The aim is to examine histopathological changes and expression of epidermal growth factor receptor (EGFR) in tracheal epithelia caused by application of topical mitomycin-C (MMC) in rabbit model after the tracheotomy procedure. The conventional tracheotomy was performed in 16 rabbits. They were randomly divided into two equal groups. The first group was applied MMC at a concentration of 0.4 mg/ml around tracheotomy for 5 min, and the other group was not taken a treatment as a control. The animals were sacrificed at the end of 4 weeks. Their tracheas were evaluated with H&E and Masson's trichrome histochemically, and with antiepidermal growth factor receptor immunohistochemically. Results showed that there was no significant difference between MMC and control group for inflammatory cells ( P = 0.09). The numbers of fibroblasts and subepithelial tissue thickness in the group exposed to MMC were significantly lower than the control group ( P < 0.05). In contrast, the percentage of EGFR in the application of MMC group was significantly higher than the control group ( P < 0.05). The application of topical MMC on airway epithelia after tracheotomy showed significant elevation in the levels of epithelial EGFR expression compared to controls in a rabbit model. The activation of epithelial EGFR may facilitate epithelial healing, but further studies are needed to assess the effect of topical MMC on respiratory epithelia.

Topical Mitomycin-C for subepithelial fibrosis after refractive corneal surgery

ObjectiveTo determine the effectiveness of mitomycin-C (MMC), 0.02%, in preventing recurrence of corneal subepithelial fibrosis after debridement and/or keratectomy in patients who have undergone refractive corneal surgery. DesignNoncomparative case series. ParticipantsEight eyes of five patients with corneal subepithelial fibrosis who had previously undergone radial keratotomy (n = 4) or photorefractive keratectomy (n = 4). InterventionAll eyes underwent epithelial debridement followed by a single intraoperative application of MMC (0.02%) for 2 minutes followed by saline irrigation. The eyes were then patched, or a bandage contact lens placed until epithelial healing was complete. Main outcome measuresCorneal clarity and best-corrected visual acuity (BCVA). ResultsIn all cases, the cornea remained clear with no recurrence throughout the follow-up period (6–25 mos., mean, 13.8 mos). No adverse reactions were reported. BCVA improved in all cases. ConclusionsSubepithelial fibrosis can be a visually disabling condition after refractive corneal surgery. Topical application of MMC (0.02%) may be a successful method of preventing recurrence of subepithelial fibrosis after debridement.