Topical Application Of Mitomycin Research Articles

Prevention of Epidural Fibrosis in Rats by Local Administration of Mitomycin C or Daunorubicin.

Epineural adhesion after peripheral nerve surgery is common. The purpose of this study was to evaluate the macroscopic and histopathologic effects of topical mitomycin C and daunorubicin on epineural scar formation. In this study, we used 15 rats (30 nerves). Two test groups and one control group were created. Sciatic nerve exposure was created bilaterally in each group (30 nerve examinations in total). In experimental group 1, cotton pads that had absorbed mitomycin C (0.5 mg/ml) were placed onto the nerves for 5 minutes while in experimental group 2, cotton pads that had absorbed daunorubicin (0.2 mg/ml) were placed onto the nerves for 5 minutes and cotton pads that had absorbed saline were applied to the control group. Eight weeks after the first surgery, surgical dissection was performed for the evaluation of neurolysis sites. Epineural adhesions were classified utilizing a numerical grading layout. We did not find any adverse effect with topically applied mitomycin C and daunorubicin. Within the 3 groups, no significant difference was seen in skin and fascia-muscle cavity closure (p > 0.05). Macroscopically, mitomycin C and daunorubicin decreased the adhesion of sciatic nerve to adjacent structures. There was intensive epineural scar formation in the control group. Scar tissue thickness and fibroblast/fibrocyte cell number were less in the two test groups compared with the control group (p < 0.001). There was no statistical difference between the two test groups. Epineural scar formation after peripheral nerve surgery may be reduced by using topical application of mitomycin C and daunorubicin.

Mitomycin C in the Therapy of Recurrent Esophageal Strictures: Hype or Hope?

Esophageal strictures refractory to conservative treatment represent a major problem in children. The application of Mitomycin C to the site of stricture has been introduced, but the experience with this novel approach remains very limited. Systematic review of publications on the topical application of Mitomycin C in children with persistent esophageal stricture. We identified 11 publications including 31 cases. The underlying cause of stricture was caustic ingestion in 19 (61.2%), esophageal surgery in 7 (22.6%), and others in 5 children (16.2%). The median age of the patients was 48 months (range 4 to 276 months). In the majority of cases cotton pledgets soaked in solution of Mitomycin C were applied endoscopically. Various other techniques such as drug-eluting stents were used. Mitomycin C was applied from 1 to 12 times within intervals from 1 to 12 weeks. The concentrations of Mitomycin C varied considerably between 0.1 and 1 mg/mL. After a mean follow-up time of 22 (6 to 60) months complete relief of symptoms was reported for 21 children (67.7%), and 6 (19.4%) had a partial relief. In four children (12.9%) Mitomycin C treatment failed. No direct or indirect adverse effects were reported. The short-term results of topical Mitomycin C application for refractory esophageal stricture reported in the literature are very encouraging. Prospective studies are mandatory to determine the optimal time points, dosage, and modalities of treatment before a recommendation can be given.

Efficacy of preoperative injection versus intraoperative application of mitomycin in recurrent pterygium surgery

Purpose:To determine the efficacy of preoperative subconjunctival injection of mitomycin C a day before surgery in the management of recurrent pterygium.Materials and Methods:Randomized comparative case series. Fifty eyes with recurrent pterygium were randomly divided into two groups; the mitomycin injection group (25 eyes) and the mitomycin application group (25 eyes). The mitomycin injection group underwent preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before bare sclera pterygium excision surgery. The mitomycin application group underwent bare sclera pterygium excision with topical application of mitomycin C (same concentration).Results:At one year of follow-up, 24 of 25 eyes (96%) in the mitomycin injection group and 23 of 25 (92%) eyes in the mitomycin application group were free of recurrence. The difference was statistically insignificant. As regards postoperative complications, delayed epithelization (more than two weeks) occurred in two eyes (8%) in the mitomycin injection group and in one eye (4%) in the mitomycin application group. Scleral thinning was reported in one eye (4%) in the mitomycin application group which resolved within three weeks after surgery, no other serious postoperative complications were reported.Conclusion:Preoperative subconjunctival injection of mitomycin C in low dose (0.1 ml of 0.15 mg/ml) a day before pterygium surgery is a simple and effective modality for management of recurrent pterygium. It has the advantage of low recurrence and complications’ rate.

Needling Augmented With Topical Application of Mitomycin C for Management of Bleb Failure

To study the effect of topical application of mitomycin C on enhancing the efficacy of needling in the management of bleb failure. Thirty-six eyes of 32 consecutive patients with an intraocular pressure over 21 mmHg, without bleb or with a thick, flat bleb after the second postoperative month after trabeculectomy, were included in the study. Needling with mitomycin C was performed in the other 18 eyes with bleb failure (group A) and needling without antimetabolite was performed in 18 eyes (group B). Topical application of mitomycin C (0.4 mg/mL) with a microsponge over the conjunctiva at the failed bleb for 5 minutes (group A) was performed; after irrigation, the needling procedure was the same in both groups. A 30-gauge needle was used to perforate the area of subconjunctival and subscleral fibrosis and to reestablish flow; conjunctival puncture was at least 7 mm away from the bleb and no sutures were taken after needling. Follow-up was performed for 1 year after needling. Overall, 55 needling procedures were performed; needling was done twice in 17 eyes in group B, whereas only 2 eyes needed more than 1 needling procedure in group A. The difference was statistically highly significant, and the mean follow-up was 8.9 ± 3.7 months. Mean intraocular pressure was 28.9 ± 4.2 mm Hg and 27.8 ± 4.7 mm Hg in group A and group B respectively before any intervention; this decreased to a mean of 19.8 ± 2.7 mm Hg and 20.5 ± 4.8 mm Hg respectively without medication after 6 months of last needling. Complications included diffuse corneal punctate epitheliopathy lasting for 2 to 3 weeks (2 eyes in group A), subconjunctival hemorrhage (3 eyes in each group), and hyphema (2 eyes in each group). Topical application of mitomycin C with needle revision seems to be an extremely effective way to revive failed filtration surgery. The incidence of complications related to mitomycin C was minimal.

Significance of adjunctive mitomycin C in endoscopic dacryocystorhinostomy

Purpose The purpose of this study is to observe the effect of intraoperative topical application of mitomycin C (MMC) on the results of endoscopic dacryocystorhinostomy. Design This is a prospective, randomized, controlled, single-blind study. Settings Hospitalized treatment was done in a tertiary medical college hospital and research center that deals with a predominantly rural population. Patients Patients with primary acquired postsaccal obstruction causing chronic dacryocystitis were considered. Methods A total of 38 patients were randomized into either a mitomycin group or a control group. Both of these groups were subjected to an identical surgical procedure, except that 0.2 mg/dL of MMC was used in the mitomycin group, whereas normal saline was used in the control group. The follow-up period was at least 6 months. An asymptomatic patient with a visible stoma at nasendoscopy and free flow of saline into the nose with lacrimal syringing after 6 months after surgery was used as criteria for defining a successful result. Results The success rate was 82.3% when MMC was used and 85.7% among the controls ( P > .05). Granulations, adhesions, and obliterative sclerosis occurred in a similar number of patients of both groups. However, granulations and adhesions did not have a bearing on the success rate in either group. Conclusion Mitomycin C did not appear to influence the occurrence of granulations, synechiae, or obliterative sclerosis, nor did it alter the success rate significantly.

Post-Intubation Tracheoesophageal Fistula with Posterior Glottic Web

Tracheoesophageal fistula (TEF) after prolonged intubation could present as chronic aspiration and could be mistaken as unilateral or bilateral vocal fold palsy, especially when there was combined posterior glottic synechia. We present a case of post-intubation TEF which was successfully treated with tracheal resection and anastomosis with primary esophageal closure. The accompanying posterior glottic web was treated by endoscopic technique of web lysis, with topical application of mitomycin C solution.

Role of mitomycin C in reducing keloid recurrence: patient series and literature review

To study the role of mitomycin C in reducing keloid recurrence. Prospective, randomised, controlled trial. Tertiary care referral centre. Case series of 20 patients presenting with 26 pinna swellings, mostly following ear piercing. We used the technique of surgical shave excision combined with topical application of mitomycin C and secondary wound healing, in all 26 pinnae. Patients were followed up six to 24 months post-operatively. No recurrences were noted during this period. Keloids are fibrotic lesions resulting from abnormal wound healing. The uncontrolled proliferation of normal tissue healing processes results in scarring that enlarges well beyond the original wound margins. Successful treatment of keloids remains a challenge because this disease process has a high propensity for recurrence. Various therapies have previously been reported, and success rates are highly variable. We believe that shave excision followed by topical mitomycin C application is a promising treatment option for the management of pinna keloids.

Successful treatment of tracheal stenosis by rigid bronchoscopy and topical mitomycin C: a case report

Tracheal stenosis is a known complication of prolonged intubation. It is difficult to treat and traditional surgical approach is associated with significant risk and complications. Recurrent stenosis due to granulation tissue necessitates repeated procedures. We describe a case of short web-like tracheal stenosis (concentric membranous stenosis less than 1 cm in length without associated cartilage damage) managed by a minimally invasive thoracic endoscopic approach. Topical application of Mitomycin C, a potent fibroblast inhibitor reduces granulation tissue formation and prevents recurrence.

Técnicas de dilatação broncoscópica e aplicação tópica de mitomicina C no tratamento da estenose traqueal pós-entubação – A propósito de dois casos clínicos

Tracheal stenosis follows any injury to the airway mucosa, such as ischaemic, traumatic and other injuries.The treatment of tracheal stenosis remains a challenging problem despite all the advances in endoscopic and surgical techniques. Scar formation and reestenosis are the main causes of treatment failure.The authors present two cases of successful treatment of a tracheal stenosis after tracheal injury from pro longed oro-tracheal intubation / tracheostomy following dilatation with rigid broncoscope and laser therapy, associated with topical application of mitomycin C as an adjuvant treatment.Rev Port Pneumol 2010; XVI (1): 149-156

Congenital glottic web: Management and anatomical observation

Congenital anterior glottis web is a rare congenital laryngeal anomaly presenting usually by either dysphonia or airway obstruction. Several ways for managing this condition have been proposed including endoscopic, as well as external techniques. The purpose of this study is to present our experience and to review the experience of others with cases of congenital glottic web regarding their diagnosis, classification and management. It is a retrospective study, which included six infants and children; two groups were identified; first group included 3 patients who were treated by endoscopic laser lysis of webs, followed by topical application of mitomycin C (MMC) to the fresh wound, and the other group included 3 patients who underwent open surgical correction, by Laryngotracheal reconstruction (LTR). Information recorded included; age, sex, presentation, grading of lesions, surgery performed, residual web, and outcome. Assessment and documentation of subglottic extension independent from the glottic extension of the web was also done. All webs were grade 2, 3 and 4 according to Cohen's classification. We observed in five cases that high grade webs (grade 3 and 4) usually had thick subglottic extension, but in one case (case 2 laser) high grade web (grade 4) had thin subglottic extension. Complications included; two recurrences one after laser surgery and the other one after LTR. All appropriate patients were decannulated post LTR. Use of laser and MMC is good in thin glottic webs; LTR is indicated in glottic webs with thick subglottic extension. Not all high grade webs have thick subglottic extension. So, thickness of web and subglottic extension has to be assessed during microlaryngeal surgery, by laser incision and examination of web thickness to determine the appropriate management.

Die topische Applikation von Mitomycin C in der Behandlung von Stenosen und Narben in Hohlorganen in der Hals-Nasen-Ohrenheilkunde – Ein Erfahrungsbericht aus 10 Jahren

The antibiotic und antitumoral effect of Mitomycin C (MMC), a derivative of Streptomyces caespitosus, has been known since 1956. Besides its use as an adjunction in the treatment of breast, lung and prostate cancer, or as a second-line cytostatic drug for head and neck squamous cell carcinoma (HNSCC), since 1963, MMC has also been successfully used in the suppression of post-operative scar formation, particularly in the field of ophthalmology. This is due to its modulation of fibroblast activity, which enables decreased scarring and fibrosis. In this résumé, we wish to recapitulate our long years of experience in the topical application of Mitomycin C in the treatment of scar formation and stenosis in head and neck organs. A retrospective analysis on the basis of clinical disease courses and findings (image documentation, questionnaires, pulmonary function tests) covering an examination period of 10 years, was performed on 40 patients with stenosising lesions and a mean age of 54 years. The fields of application included laryngeal, tracheal, oesophageal stenosis and stenosis of the external ear canal and the choane. After combined application of MMC and surgical intervention in cases of recurrent stenosising processes in head and neck organs, especially the larynx and the trachea, a sustained improvement was achieved in the pre-operative stenosis level as well as in the pre-operative, severely limited, forced inspiratory volume in 1 second (F1V1). The topical application of MMC appears to be an effective adjunction as a concept of treatment for stenosising, scar-forming lesions. This topical application, however, is not a substitute for correct diagnosis and appropriate surgical treatment. It must be regarded as a purely adjunctive manoeuvre. During the 10 years in which it was used, the clinical findings confirmed an enhancement in the containment of complex cases without the occurrence of any complications.

Primary Sebaceous Carcinoma of the Corneaoscleral Limbus With Pagetoid Recurrence

We report a sebaceous carcinoma confined to the corneoscleral limbus without involvement of the eyelid. A 60-year-old man, who showed multiple masses on the corneaoscleral limbus and limbal ulceration but with normal eyelids, underwent surgical en-bloc excision of the masses. Histopathologic examination revealed a sebaceous carcinoma. Three weeks after excision, multiple pagetoid recurrences were found along the bulbar conjunctiva 2 mm away from the limbus. After the application of topical mitomycin C, the pagetoid spread regressed completely. After a 2 year follow-up, no other local or systemic recurrences were observed. This report shows that the ulcerative mass which is confined to only the corneoscleral limbus may be a sebaceous carcinoma even without eyelid involvement. Topical mitomycin C may be effective for treating pagetoid spread of sebaceous carcinoma of limbal origin.

The effect of mitomycin C as fibrosis preventive agent during craniectomies

Object. The authors conducted a study to determine the effectiveness of mitomycin C (MMC) in preventing epidural fibrosis in rats which underwent craniectomy.Methods. Craniectomies were performed in the right frontoparietal region; after the procedure the animals had been divided in 2 groups of 10 each. Cotton pads soaked with 0.1 mg/ml MMC or saline (control) were applied to the operative sites. Four weeks after craniectomy the rats were sacrificed, and epidural fibrosis was evaluated histologically. The dura mater thickness, the density of epidural fibrosis, arachnoidal involvement, and bone regeneration were determined.Results. No obvious adhesion formed in the rats in the MMC group, but severe epidural adhesions were found in control group. The duramater thickness, the density of epidural fibrosis, and arachnoidal involved rat number in the MMC group were significantly lower than in control groups.Conclusions. Epidural fibrosis can be a devastating condition that forms after craniectomy. Topical application of mitomycin C may be a successful method of preventing epidural fibrosis following craniectomy.

Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence

Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence

Tracheo-carinal reconstructions using extrathoracic muscle flaps☆

Prospective evaluation of tracheo-carinal airway reconstructions using pedicled extrathoracic muscle flaps for closing airway defects after non-circumferential resections and after carinal resections as part of the reconstruction for alleviation of anastomotic tension. From January 1996 to June 2006, 41 patients underwent tracheo-carinal airway reconstructions using 45 extrathoracic muscle flaps (latissimus dorsi, n=25; serratus anterior, n=18; pectoralis major, n=2) for closing airway defects resulting from (a) bronchopleural fistulas (BPF) with short desmoplastic bronchial stumps after right upper lobectomy (n=1) and right-sided (pleuro) pneumonectomy (n=13); (b) right (n=9) and left (n=3) associated with partial carinal resections for pre-treated centrally localised tumours; (c) partial non-circumferential tracheal resections for pre-treated tracheal tumours, tracheo-oesophageal fistulas (TEF) and chronic tracheal injury with tracheomalacia (n=11); (d) carinal resections with the integration of a muscle patch in specific parts of the anastomotic reconstruction for alleviation of anastomotic tension (n=4). The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. The patients were followed by clinical examination, repeated bronchoscopy, pulmonary function testing and CT scans. The minimum follow-up time was 6 months. Ninety-day mortality was 7.3% (3/41 patients). Four patients (9.7%) sustained muscle flap necrosis requiring re-operation and flap replacement without subsequent mortality, airway dehiscence or stenosis. Airway dehiscence was observed in 1/41 patients (2.4%) and airway stenosis in 1/38 surviving patients (2.6%) responding well to topical mitomycin application. Follow-up on clinical grounds, by CT scans and repeated bronchoscopy, revealed airtight, stable and epithelialised airways and no recurrence of BPF or TEF in all surviving patients. Tracheo-carinal airway defects can be closed by use of pedicled extrathoracic muscle flaps after non-circumferential resections and after carinal resections with the muscle patch as part of the reconstruction for alleviation of anastomotic tension.

Comparison Between Mitomycin C and Chitosan for Prevention of Anterior Glottic Steno After CO2 Laser Cordectomy in Dogs

To compare the effectiveness of an immediate application of topical mitomycin C (MMC) with chitosan for prevention of anterior glottic stenosis (AGS) after microsurgical resecting of both vocal fold with CO2 laser, including the anterior commissure, in a canine model. Prospective randomized experimental study. Twenty-four canine larynges were injured by a microresecting procedure of both vocal folds with a CO2 laser. The dogs were randomly divided into three groups for treatment, respectively with MMC, chitosan, or isotonic sodium chloride solution (control) for 5 minutes immediately after surgery. One week after the initial surgery, three dogs in each group were randomly selected, the ultrastructures of the fibroblasts were examined with a transmission electronic microscope, and expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) were evaluated by enzyme-linked immunosorbent assay (ELISA). Three weeks after surgery, the remaining dogs' glottic web were lysed and repeatedly treated with MMC, chitosan, or isotonic sodium chloride solution. The glottic wound healing and AGS formation were examined every week, and all larynges were harvested and examined histologically 6 weeks after the initial surgery. Results included 1) transmission electronic microscope examination of the ultrastructures of the fibroblasts indicated that both MMC and chitosan inhibited the proliferation of fibroblast; 2) the expression of bFGF and TGF-beta1 increased both in the MMC group and the chitosan group, and the expression of bFGF in the chi-tosan group was higher than in the MMC group (P = .010), while the expression of TGF-beta1 was lower (P = .000);3) the extent of AGS formation was decreased both in the MMC group and the chitosan group, while it was less in the chitosan group than in the MMC group (P = .047); 4) the grade of collagen content between the MMC group and the chitosan group was not significantly different (P = .5). Chitosan is more effective in preventing AGS after CO2 laser cordectomy than MMC.

A comparison of the effectiveness of mitomycin C and 5-fluorouracil in the prevention of peridural adhesion after laminectomy

The effectiveness of the topical application of mitomycin C (MMC) or 5-fluorouracil (5FU) in preventing peridural adhesion after laminectomy was compared in this study. Laminectomies were performed at L-1 in 30 rats. Cotton pads soaked with 0.1 mg/ml MMC, 25 mg/ml 5FU, or 9 mg/ml saline (control) were applied to the operative sites. To evaluate neurological deficits pre- and postoperatively, somatosensory evoked potentials were monitored and the Basso-Beattie-Bresnahan locomotion test was performed. Four weeks postlaminectomy the rats were killed, and peridural scar adhesion was evaluated histologically. The level of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts were determined. The degree of peridural adhesion was classified according to the Rydell standard. No obvious adhesion formed in the rats in the MMC group, but severe peridural adhesions were found in those in the 5FU and control groups. The content of hydroxyproline, the area of peridural scar tissue, and the number of fibroblasts in the MMC group were significantly lower than those in the 5FU and control groups. The topical application of MMC rather than 5FU may be a successful method of preventing postlaminectomy peridural adhesions.

Topical application of mitomycin C in the treatment of esophageal and tracheobronchial stricture: a report of 2 cases

We present 2 cases of successful treatment of recurrent anastomotic strictures using a topical application of mitomycin C. In the first case, a 4-year-old boy had a cervical cyst excised, which appeared to be an ectopic gastric mucosa. He consequently presented severe stenosis at the origin of the cervical esophagus that needed repeated balloon dilatations. The second case is about a 12-year-old girl who presented a traumatic complete rupture of the right mainstem bronchus managed by primary repair, with subsequent anastomotic stricture. Both patients were successfully managed with topical application of mitomycin C (1 mg/mL), and needed no more dilatations.

Topical application of mitomycin after shave-removal is an effective therapy for patients with keloid scars,

Topical application of mitomycin after shave-removal is an effective therapy for patients with keloid scars,

Application of topical mitomycin C to the base of shave-removed keloid scars to prevent their recurrence

Keloid scars are formed by over-activity of fibroblasts producing collagen and they cause significant morbidity both from their appearance and from their symptoms. Existing treatments are often unsatisfactory. Topical mitomycin C is known to inhibit fibroblast proliferation. To determine whether application of mitomycin C to the base of shave-removed keloids would prevent their recurrence. Ten patients had all or part of their keloid shave-removed. After haemostasis topical mitomycin C 1 mg mL(-1) was applied for 3 min. This application was repeated after 3 weeks. The keloids were photographed before treatment and the patients were reviewed every 2 months for a total of 6 months when a final photograph of the keloid site was taken. The patients and the Clinical Trials Unit staff scored the outcome on a linear analogue scale of 0-10, where 0 = disappointed and 10 = delighted. The pretreatment and 6-month post-treatment photographs were also assessed by two dermatologists who were not involved in the clinical trial. Four of the 10 patients were delighted with the outcome of treatment and only one was disappointed. On average there was an 80% satisfied outcome. This new treatment of keloids has been shown to be effective in the majority of patients but further studies are required to confirm this benefit.