Mitomycin C Application Research Articles

The Role of Mitomycin C in Preventing Synechia and Stenosis after Endoscopic Sinus Surgery

Synechia and stenosis formation after endoscopic sinus surgery (ESS) represents a potential source of surgical failure. Mitomycin C (MMC) has been used successfully in other fields to decrease postoperative scar formation. We hypothesize that the topical application of MMC reduces the incidence of stenosis and synechia formation after ESS. This study is a randomized, controlled, single-blinded study based in a tertiary care teaching hospital. After routine ESS, a pledget soaked in MMC (0.5%) was randomly placed into the middle meatus of one nasal cavity for 5 minutes and a pledget soaked in saline was placed in the contralateral side in each patient. A blinded observer followed the patients for any evidence of stenosis or synechia formation. The medical records of enrolled patients were reviewed for demographics, diagnosis, prior surgery, type of sinus surgery, complications, incidence of stenosis/synechia, and need for further procedures. Twenty-nine patients were included in the final analysis. The mean follow-up period was 15 months (range, 3-32 months). There were no complications in this series. Eight patients experienced 10 episodes of synechia formation and one patient experienced 1 episode of synechia formation and 1 episode of stenosis of the maxillary sinus ostium. Seven of the 12 episodes of synechia/stenosis occurred on the side of the MMC application and the remaining 5 episodes occurred on the side opposite to the MMC application. This difference was not statistically significant. The topical application of MMC did not decrease the incidence of stenosis and synechia formation after ESS.

Application of mitomycin-c for head and neck keloids

Objectives: Keloids of the head and neck are a relatively common entity in darkly pigmented individuals, occurring in 5%-15% of skin wounds. Despite a wide range of available treatments, recurrence rates remain high. This study reviews the effectiveness of using a combination of surgical excision and topical mitomycin c (a chemotherapeutic agent that inhibits fibroblast proliferation) for the treatment of head and neck keloids. Methods: Ten consecutive patients, treated by the same surgeon, underwent the combination of surgical excision of keloids and the application of topical mitomycin-C. The patients were all evaluated preoperatively and were then followed long-term (6–14 months) for recurrence. Results: The combination of surgical excision with the application of topical mitomycin C was highly effective in treating head and neck keloids in this study. There were 9 of 10 patients who had successful excision of the keloid lesions with no recurrence, for a success rate of 90%. One of the 10 patients treated with surgical excision and topical mitomycin-C had a recurrence. Conclusions: The successful treatment of keloids continues to be a challenging endeavor as there is a high propensity for recurrence of this disease process. There have been many reports on various therapies in the literature and success rates are highly variable. In this series of patients, the combination of surgical excision and topical mitomycin C was 90% successful. These are promising results for an alternative treatment option in the management of head and neck keloids.

The effects of topical and injected mitomycin c on wound healing

Objectives: To determine the effect of topical and injected Mitomycin C (MMC) on skin wound healing by examining wound strength and histology. Methods: Paramedian incisions were placed on the back of each of 18 adult male Sprague-Dawley rats. The wounds were treated with topical MMC, intradermal MMC (0.5 mg/mL), or normal saline and closed with staples. Two animals in each study arm were sacrificed at 1 and 2 weeks, and 1 and 6 months. After wound harvest 1 section was reserved histologic examination (blinded) with H & E staining and TFG-B1-specific immunohistochemical staining. Using a tensiometer, the remaining wound sections were used to evaluate the force needed to cause wound dehiscence. Kruskal-Wallis and Mann-Whitney tests were used for statistical comparison. Results: Application of topical MMC resulted in decreased wound integrity compared with saline-treated animals at 1 week ( P < 0.001), 2 weeks ( P < 0.001), and 1 month ( P < 0.001). Intradermal MMC showed decreased wound integrity 1 week ( P < 0.001), 2 weeks ( P > 0.001), and 1 month ( P > 0.001). (Six month data pending.) Small areas of skin necrosis occurred in 7 of 8 animals receiving intradermal MMC, and no animals in the other groups. There was no consistent difference in fibroblast proliferation or concentration of TGF-B1 between saline and MMC-treated animals. Conclusions: Intradermal MMC can cause skin necrosis. MMC-treated wounds had decreased wound strength compared to controls. Despite the wound strength changes, no consistently identifiable histological changes in fibroblast proliferation or TGF-B1 expression was noted. This data suggest cautious use of MCC in clinical situations when wound breaking strength is critical.

Early corneal edema following topical application of mitomycin-C

Purpose: To determine the effect of mitomycin-C (MMC) on the cornea after a single intraoperative application. Setting: Department of Ophthalmology, Far Eastern Memorial Hospital, Ban-Chiao, Taipei, Taiwan. Methods: Mechanical epithelium debridement of the central 10.0 mm of the cornea was performed in 63 pigmented rabbits. One group of corneas (MMC1, n = 42) was soaked with MMC 0.01% solution for 2 minutes; the second group (MMC2, n = 42) was soaked with MMC 0.02% solution for 2 minutes. Control corneas (n = 42) were soaked with balanced salt solution for 2 minutes. Changes in the central corneal thickness, clarity, epithelial defect size, endothelial cell density, and endothelial apoptosis in the 3 groups were examined on days 0, 1, 2, 3, 5, 7, and 14. Results: There was a dose-dependent increase in corneal thickness, decrease in corneal clarity, and increase in endothelial apoptosis after a single intraoperative application of MMC. The endothelium was significantly swollen and became pleomorphic and polymegethic with a concomitant decrease in endothelial cell density, also in a dose-dependent manner. Conclusions: A single application of MMC on the corneal surface caused dose-dependent corneal edema and endothelial apoptosis in the rabbit model. Further clinical study of human eyes is warranted.

Rhinoscleroma: A case report and update on medical and surgical management

Objectives: Rhinoscleroma is a chronic, progressive, granulomatous infection caused by Klebsiella rhinoscleromatis. The bacteria can infect the upper and/or lower airways, with the sinonasal cavity being affected 95%-100% of the time. We present the case of a 42-year-old Hispanic man who presented with Stage 3 rhinoscleroma, resulting in nasopharyngeal, glottic, and subglottic stenosis. Methods: The patient was taken to the operating room for direct microlaryngoscopy. A posterior cordotomy of the left vocal fold and laser radial incisions/dilation of the subglottis were performed along with topical application of Mitomycin-C. Results: Biopsies of the nasopharygeal and subglottic lesions showed inspissated mucin with foamy histiocytes, gram negative bacilli, and acute and chronic inflammation with fibrosis. Cultures were positive for Klebsiella rhinoscleromatis, sensitive to gatifloxacin. These pathological findings were consistent with Stage 3 rhinoscleroma. The patient was treated with a 6-month course of gatifloxacin. Purulent rhinorrhea and airway difficulties were improved at 6 weeks and resolved at 6 months. Conclusion: We report a case of synchronous rhinoscleromatous lesions. A combination treatment of surgical laser debridement, Mitomycin-C and long-term fluoroquinolones appears to be effective in treating this condition. There are 3 stages of rhinoscleroma and with prompt recognition and early treatment, the natural history of the disease can be halted. The advantages of fluoroquinolones over traditional antibiotic treatment for this condition (tetracycline) include low incidence of side effects, once daily dosing and concentration within the macrophages, the region of bacterial replication. When surgical treatment is necessary, stenosis can be effectively managed with CO 2 laser treatments and Mitomycin-C.

Airway complications from topical mitomycin-c

Problem: Topical application of mitomycin-C appears to be a useful adjunct in reducing cicatricial scarring of the airways. Human and animal studies have demonstrated the efficacy and safety of mitomycin topically in the treatment of airway stenosis at concentrations ranging from 0.4 mg/cc to 10 mg/cc. Although no reports of mitomycin toxicicity have been reported in the otolaryngology literature, the ophthalmologic literature has documented serious, vision-threatening complications resulting from the use of topical mitomycin-C. The purpose of this study is to report complications related to mitomycin-C use in the treatment of glottic and subglottic stenosis. Risk factors associated with these complications are identified. Methods: A retrospective chart review of all patients treated by the senior author for glottic, subglottic, and tracheal stenosis during a 4-year period was performed to determine incidence of complications. Variables studied were: patient age and gender, location and severity of stenosis, medical comorbidities, length of procedure, postoperative instrumentation of the airway, and mitomycin-C concentration. Results: Sixty-six cases of adjuvant topical mitomycin-C use following laser laryngoscopic treatment and dilation for upper airway stenosis were identified in a total of 45 patients. Complications due to local toxicity of mitomycin-C occurred in 4 patients of 66 (or 6%), manifested by accumulation of fibrinous debris at the operative site, resulting in partial airway obstruction, and the need for emergent airway intervention. A significantly higher percentage of complications occurred when supersaturated mitomycin-C (10 mg/cc) was used ( P < 0.05). Conclusion: Caution should be exercised when using topical mitomycin-C in the treatment of airway stenosis. Local tissue effects from fibroblast inhibition may, in some instances, lead to the accumulation of fibrinous exudates that can obstruct the airway in the early postoperative period. Significance: This is the first study describing serious complications and potential risk factors related to topical mitomycin-c use in the endoscopic treatment of upper airway stenosis. Support: None reported.

How to repair total nasopharyngeal stenoses with functional obturators and mitomycin-c

Objectives: Severe nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP) is a dreaded complication. Very little is written about successful treatment as attempts at correction frequently fail. Severe stenosis of the nasopharynx drastically worsens speech, swallowing, and obstructive sleep apnea (OSA). We present our successful experience with severe stenosis focusing on a simple functional repair utilizing topical Mitomycin-C as well as differing daytime and nighttime palatal obturators. Methods: Three adults with near total nasopharyngeal stenosis secondary to UPPP were referred to our institution after multiple failed attempts at repair. Each presented with severe OSA on polysomnogram (PSG) with excessive daytime somnolence and voice and swallowing complaints. Under general anesthesia, a CO 2 laser creates an opening in the nasopharynx. Removable and adjustable palatal obturators are fashioned to keep the nasopharynx open with a daytime insert piece with a small obturator hole for diminished velopharyngeal insufficiency and a nighttime one without an insert to maximize recumbent airflow. Obturators are removed 6 months later with topical application of mitomycin-C as a fibroblast inhibitor. All patients were followed clinically for over 1 year and received posttreatment PSG. Results: All patients experienced resolution of their stenosis. Swallowing and voice complaints resolved. OSA was either eliminated or any residual OSA was successfully treated with nasal CPAP. Serial videoendoscopic images throughout the treatment phase demonstrate the effectiveness of this new technique. Conclusions: Severe nasopharyngeal stenosis is a rare but devastating complication of UPPP. We introduce a simple technique utilizing functional palatal obturators and topical mitomycin-C and describe our success with this treatment algorithm.

Effectiveness of postoperative measures in reducing adhesions after ESS: A systematic review

Problem: Adhesions are one of the most common causes for endoscopic sinus surgery (ESS) failures. Though meticulous postoperative debridement as well as various other interventions have commonly been undertaken partly to prevent the development of this complication, the basis behind these time-consuming and costly practices is largely empirical. We therefore set out to evaluate the evidence supporting postoperative debridement and other postoperative measures in preventing adhesion formation after ESS. Methods: The Cochrane Controlled Trials Register, MEDLINE, EMBASE, and the references of relevant articles were searched. Selection criteria included all randomized controlled trials that compared adhesion rates of adult ESS patients who were subjected to any form of postoperative intervention versus no or alternative intervention. Results: A total of 4 relevant research papers were identified. The interventions evaluated were all different and included postoperative debridement, 2 different types of hyaluronic acid sinus dressing and topical mitomycin-C application. All of the studies showed no significant difference in preventing adhesions, except for the study evaluating cross-linked hyaluronic acid dressing, which showed a statistically significant benefit in reducing adhesion formation (overall adhesion score 1.2 + 0.1 versus 2.1 + 0.1, P = 0.0001). Conclusion: The evidence available thus far seemed to suggest that the majority of current postoperative interventions, including the common practice of intensive postoperative sinus cleaning, did not significantly reduce adhesions. However, further evaluation to clarify the usefulness and role of these various measures is required. In addition, standardized intervention and outcome measures need to be devised to ensure quality data collection. Significance: This systematic review revealed that current post-ESS care regimens to reduce adhesion formation are not evidence based. It highlights the need for standardizing reporting parameters, and collecting more good quality data. Until then, postoperative care remains empirical. Support: None reported.

Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits

purpose To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits.methods Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (10 animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope.results MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes.conclusions MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.

The successful management of congenital laryngeal web with endoscopic lysis and topical mitomycin-C

Laryngeal web is a rare congenital anomaly. The primary goals of management for congenital laryngeal web are to provide a patent airway and to achieve a good voice quality. However, vocal cords have a tendency for fibrosis and granulation tissue formation after surgical interventions. Traditionally, the treatment of choice for laryngeal web is laryngofissure and placement of a stent or keel. This report presents the successful management of a congenital laryngeal web in a 10-month-old boy with endoscopic lysis and topical mitomycin-C application.

Does Topical Mitomycin-C Improve the Surgical Outcomeof Bilateral Congenital Choanal Atresia Repair?

Bilateral congenital choanal atresia (CCA) in newbornscarries significant morbidity and mortality. Many surgical approaches have been described for its correction but none of the approaches have proved superior in preventing postoperative granulation tissue and restenosis. Recently, topical Mitomycin C (MMC) has been used intraoperatively to prevent the formation of granulation tissue and restenosis in choanal atresia repair. We report a series of three consecutive patients who underwent bilateral CCA repair and received topical MMC intraoperatively. We have used topical MMC in CCA repair for the first time in Qatar and report the outcome of these patients. Case 1 was a preterm child (29 gestational weeks) who underwent transnasal repair. Case 2 had CHARGE association and case 3 had no other anomalies, both of whom underwent transpalatal repair. In case 1, we had used topical MMC \ during revision surgery with improved outcome. In cases 2 and 3, topical MMC was applied during primary repair and in addition both received a second application selectively at the margins of the choanae 6 weeks after stent removal. Case 3 needed further dilatation of the choanae four months after second application of topical MMC. None of our patients developed any local or systemic side effects. To our knowledge, bilateral CCA repair in a 29 weeks gestational age child has not been reported in the literature. Our study suggests that topical MMC may be a useful adjunctive therapy in choanal atresia repair.

P.1.189 Venlafaxine and SSRIs: Pooled remission analysis

Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation. To reduce the recurrence rate, surgery is the main strategy, in combination with adjacent procedures or adjunctive therapy. One of the most common adjunctive agents, mitomycin C (MMC), is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications. A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low-density lipoprotein (LDL) receptors. In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL ([email protected]) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 μg/ml [email protected] for 24 h (MMC concentration: 0.6 μg/ml); 2) 0.2 mg/ml MMC for 5 min then cultured for 24 h after MMC removal; and 3) normal culture without any drug treatment. At 24 h, the anti-proliferative effect of [email protected] in activated pterygium fibroblasts was similar to that of MMC (cell viability: 46.2 ± 5.5% vs 40.5 ± 1.1%, respectively, P = 0.349). Furthermore, the cytotoxicity of [email protected] to normal fibroblasts with or without VEGF stimulation was significantly lower than that of traditional MMC (cell viability: 75.6 ± 4.4% vs 36.0 ± 1.5%, respectively, P < 0.001; 84.7 ± 5.5% vs 35.7 ± 1.3%, P < 0.001). The binding of fluorescently labeled [email protected] in fibroblasts was assessed using confocal fluorescence microscopy. The uptake of targeted nanoparticles in fibroblasts was time dependent and saturated at 6 h. VEGF-activated pterygium fibroblasts showed more uptake of [email protected] than normal fibroblasts with or without VEGF activation (both P < 0.001). Our data strongly suggest that [email protected] had an effective antiproliferative role in activated pterygium fibroblasts, with reduced toxicity to normal fibroblasts compared to traditional application of MMC. LDL-mediated drug delivery might have great potential in the management of pterygium recurrence.

Outcome of double-headed pterygium surgery.

To evaluate the postoperative outcome and recurrence rate of bare sclera technique combined with intraoperative application of mitomycin C (MMC) 0.02% for 5 minutes in the treatment of primary and recurrent double-head pterygia. A prospective, noncomparative interventional case series of 13 eyes in 13 patients with primary (n = 10) or recurrent double-head pterygia in one eye operated on by one surgeon (R.A.). They all had bare sclera excision combined with intraoperative application of MMC 0.02% for 5 minutes. All patients were followed postoperatively for recurrence of the lesion, aesthetic outcome, and incidence of eye complications. Mean follow-up was 36.3 +/- 3.8 months for the patients with primary and 28.4 +/- 2.7 months for the patients with recurrent double-head pterygia. There was only one recurrence in one of the three eyes in the group with recurrent pterygia (33.33%). The only significant complication observed was a pyogenic granuloma in two of the recurrent and one of the primary cases. The bare sclera technique combined with intraoperative MMC 0.02% for 5 minutes is an effective and safe procedure for double-head pterygia. This method can serve as a useful alternative to amniotic membrane transplantation in countries where the latter is not available and in patients in whom conjunctival autograft is not feasible.

Mitomycin C eliminates the short-term intraocular pressure rise found following Molteno tube implantation.

Molteno implants remain popular for treating recalcitrant glaucomas. This study aimed to assess the effect of mitomycin C (MMC) use with Molteno tube implantation upon intraocular pressure (IOP) control and complication rates. In particular, the study aimed to assess any change that MMC might have upon the postoperative hypertensive phase. A retrospective case record study was conducted of all patients undergoing double plate Molteno implant surgery by one surgeon over 5 years. Eyes with recalcitrant glaucoma unresponsive to previous surgery, or deemed unlikely to succeed with trabeculectomy, underwent double plate Molteno tube implantation. Eyes that had MMC (0.3 mg/mL, 3 min) applied to Tenon's capsule over the secondary plate were compared with eyes that underwent surgery without adjunctive MMC application. Twenty-seven eyes received MMC and were similar to 26 eyes not receiving MMC in terms of glaucoma subtype, age, sex, previous surgery, preoperative IOP and postoperative IOP lowering agents. Those not receiving MMC had raised IOP 31-90 days post implantation compared with MMC treated eyes (P < 0.01) and more often received oral antifibrosis medication (P < 0.05). Complications were no more common with MMC except for initial overdrainage. Significant systemic complications from the use of oral antifibrosis medication were common. The findings suggest a useful role for MMC. Caution is advised in case selection for MMC use. Mitomycin C treatment over the secondary plate alone permits removal of this plate if MMC-related complications occur without requiring removal of the whole implant.

Transconjunctival mitomycin-C in needle revisions of failing filtering blebs

Purpose To report the efficacy and safety of transconjunctival mitomycin-C as an adjunct to needle revision of failing filtering blebs. Design Retrospective, consecutive, noncomparative interventional case series. Participants Forty-one patients (42 eyes) undergoing bleb revisions by a single surgeon at a single institution from May 1997 to January 2001. Methods The authors retrospectively reviewed charts of 42 eyes that underwent needle revision of the failing filtering bleb using transconjunctival application of mitomycin-C. Needling of the bleb was performed with a 25-gauge needle. The site of the needle puncture was sutured and followed by application of transconjunctival mitomycin-C (0.5 mg/ml) by means of a sponge left in contact with the conjunctival epithelium for 6 minutes. A group of patients received additional subconjunctival injections of 5-fluorouracil in the postoperative period. Success was defined as a reduction in intraocular pressure of 30% without the use of antiglaucoma medications and no further surgical procedures to control intraocular pressure. Main outcome measures Intraocular pressure, visual acuity, complications, number of glaucoma medications used at the final visit. Results Mean preoperative intraocular pressure was 22.1 ± 8.0 mmHg, which was reduced by 9.6 ± 7.9 mmHg to a mean postoperative intraocular pressure of 12.5 ± 6.1 mmHg. Mean follow-up was 17.6 ± 13.5 months. Kaplan-Meier survival analysis showed a probability of continued success at 12 months of 76.1%, and at 24 months of 71.6%. The most common complication was hyphema in 7.1% of patients. Twenty-six eyes also received postoperative injections of 5-fluorouracil. Conclusions Transconjunctival mitomycin-C may enhance success of the needling procedure in failing filtering blebs.

Mitomycin C-activity effected by vitamins B1, C, E and beta-carotene under irradiation with gamma-rays.

Vitamin B1 (thiamine) can essentially effect the activity of mitomycin C (MMC), added individually or in combination with antioxidant vitamins (C, E-acetate, beta-carotene) as found in experiments in vitro (Escherichia coli bacteria, AB 1157) under irradiation with gamma-rays. The environment plays a crucial role. In airfree media vitamin B1 leads to a 2-fold increase of the MMC-efficiency, but adding vitamin C it decreases. In the presence of all vitamins (B1, C, E-ac., and beta-carotene) the MMC-action increases about 1.8-fold. In aerated media vitamin B1 causes an about 4-times increase of the MMC-efficiency, but by adding vitamin B1 and C the MMC-activity decreases by a factor of two, whereas in the presence of B1, C, E-ac., and beta-carotene it rises again to 2.6-fold. In environment saturated with N2O (conversion of e(-)aq into OH radicals) a different picture is observed. The presence of vitamin B1 or vitamin B1 + C causes a strong decrease of the MMC-efficiency, but the addition of all vitamins (B1, C, E-ac., and beta-car.) leads to a small increase of the cytostatic action. The results demonstrate the influence of vitamin B1 used individually or in combination with other antioxidants on the MMC-efficiency and the strong effect of the environment. The results are of interest for the application of MMC in radiotherapy.

Silicone nasolacrimal intubation with mitomycin-C: a prospective, randomized, double-masked study

Objective To determine if mitomycin-C (MMC) application during silicone intubation (SI) can effectively substitute for dacryocystorhinostomy (DCR) or Jones tube insertion. Design A prospective, randomized, double-masked study. Participants Twenty-four patients (7 males, 17 females; aged 2–69 years) with 27 eyes (three bilateral cases) with an obstructed lacrimal system who were candidates for DCR or Jones tube. Methods All study patients underwent SI with application in a randomized, double-masked fashion of MMC or placebo, with the former receiving 0.2 mg/ml MMC for 2 minutes before SI. Main outcome measures Clinical assessment of tearing and discharge; Schirmer I and II tests at 1, 3, 6, and 12 months; and the need for eventual DCR or Jones tube insertion. Results Follow-up ranged from 13 to 23 months (mean, 18 months; median, 17 months). Seven of the 12 eyes in the MMC group and 8 of the 15 eyes in the placebo group had a successful outcome and remained symptom free. The difference was not statistically significant ( P = 0.79). Dacryocystorhinostomy or Jones tube was performed in five eyes in the MMC group and in seven eyes in the placebo group 3 to 18 months later; all had successful outcome and no complications. Untoward effects of MMC application included a slit canaliculus and a transient conjunctival injection. A successful outcome using this combined technique does not appear to correlate with age, gender, laterality, and intraoperative bleeding observed at the punctum or for the duration of symptoms. Conclusions Mitomycin-C application during SI did not benefit outcome. Complications from such application were mild and infrequent.

Modifying Subsceral Fluid Pressure in an Experimental Model of Mitomycin-C Diffusion

Background: Episcleral application of mitomycin-C (MMC) during glaucoma filtration surgery hinders the post-operative wound healing. Diffusion through the sclera might result in a toxic effect on the ciliary body resulting in reduced aqueous humor production leading to post-operative hypotony. We developed an experimental model to investigate the influence of intraocular pressure on the diffusion of MMC through the sclera and in subscleral compartments.Methods: Scleral quadrants of 10 human donor eyes were mounted on PMMA tubes filled with saline imitating the intraocular volume. By height variation of a coupled infusion line different intraocular pressures were simulated (0, 8, 23 and 80mmHg). Additionally the model included a subscleral sponge to mimic the compartment of the ciliary body. The episcleral sides of the scleral quadrants were exposed for 1min to sponges soaked with 200μgml−1 MMC. An 8-mm-diameter scleral disk was punched out with a trephine and horizontally dissected with a kryotome. The MMC concentrations of scleral layers, epi-and subscleral sponges and the fluid within the tubes were analysed by means of high-performance liquid chromatography.Results: The MMC concentration gradually declined from the episcleral sponge (165μgml−1) to the superficial (3.3μgml−1) and deep scleral layers (1.2μgml−1), and to the subscleral sponge (0.2μgml−1). We were able to detect very small concentrations of MMC in the fluid within the PMMA tubes (0.01μgml−1).Conclusion: We developed a new experimental in vitro model for investigating transscleral MMC diffusion. The different simulated intraocular pressures had no effect on the concentration gradient through the investigated compartments of our model.

Pharmacokinetics of intra-arterial mitomycin C in the chemoembolization treatment of liver metastases with polyvinylalcohol or degradable starch microspheres.

In cancer treatment, arterial blood flow reduction by embolization combined with intra-arterial chemotherapy may be advantageous by achieving high and prolonged drug concentrations in the tumor, and lower systemic drug exposure. The pharmacokinetics of intra-arterial mitomycin C (MMC) was investigated in patients with liver metastases undergoing chemoembolization treatment. The chemoembolization treatment consisted of the use of polyvinylalcohol microspheres (ITC-Contour, diameter 150-250 micro m, irreversible vessel occlusion, 20 mg MMC, 15 patients) followed by sealing of the supplying artery with Ethibloc. Alternatively, starch microspheres (Spherex, diameter 45 micro m, biologically degradable, 10 ml of suspension containing 60 mg starch/ml, 20 mg MMC in 7 patients, 15 mg/m2 body surface in 3 patients) were used. MMC was infused over 6 min into the artery supplying the tumor. Serum MMC concentrations were determined from peripheral venous blood samples [protein precipitation with acetonitrile, reverse-phase HPLC with ultraviolet detection (C18 column, elution with 0.01 M, pH 6.5 phosphate buffer/methanol, v/v 70:30, 365 nm)]. The pharmacokinetic parameters were computed assuming an open two-compartment model and linear kinetics. The disposition parameters for MMC in patients treated with polyvinylalcohol microspheres were comparable to data from the literature (C(max)=913+/-98 ng/ml, T(max)=7.7+/-0.3 min, V(c)=0.27+/-0.03 l/kg, V(ss)=0.59+/-0.07 l/kg, Cl=757+/-67 ml/min, T(1/2 alpha)=5.8+/-0.8 min, T(1/2 beta)=50.4+/-4.1 min). There was no significant difference in the disposition parameters for MMC between patients treated with polyvinylalcohol microspheres and those treated with starch microspheres ( P>0.05). In particular, there was no significant difference in the standardized AUC between the groups; this implies that the systemic toxicity of MMC is comparable when polyvinylalcohol microspheres and ethibloc (AUC 1472+/-123 microg min/l per 1 mg MMC) or starch microspheres (AUC: 1448+/-172 microg min/l per 1 mg MMC) are used. The AUC values found in this study do not indicate a reduction in the systemic toxicity of MMC if applied intra-arterially in combination with embolizing microspheres, when compared to the AUC values in the literature for intra-arterial application without embolization, or intravenous MMC application. The amount of starch microspheres may have been too small to cause marked effects. On the other hand, there is a very wide range of AUC values reported in the literature for different application modes, and the use of such historical controls is not adequate for detecting more subtle advantages of the chemoembolization procedure, which may, however, exist.

Intraoperative episcleral versus postoperative topical application of mitomycin-C for trabeculectomies

Objective To assess the efficacy of a new application technique of mitomycin-C to enhance the outcome of filtering surgery in cases of complicated glaucoma. Design Randomized clinical trial. Participants Fifty consecutive patients scheduled for glaucoma surgery in one large surgical center. Intervention Patients underwent routine trabeculectomy. In group 1, mitomycin-C (0.05 mg/ml) was applied topically to the filtering bleb on days 1, 2, and 3 after surgery (postoperative application). In group 2, mitomycin-C (0.2 mg/ml) was applied by means of to a sponge during surgery (intraoperative application). Main outcome measures Preoperative and postoperative intraocular pressure (IOP) values, visual acuity, the need for antiglaucoma medication, previous surgical procedures, and the need for further surgical interventions were monitored. Results Sufficient follow-up data were available from 24 of 25 patients in each of the two groups. The follow-up ranged from 12 to 28 months and was evaluated at 12 months for all patients. The mean IOP decreased from 27.3 to 15.5 mmHg in group 1 and from 29.0 to 17.5 mmHg in group 2. The average number of medications decreased from 2.3 and 2.4 to 0.9 and 0.8 ( P = 0.68; t test) in groups 1 and 2, respectively, at the 12-month visit. Hypotony was more frequent in group 2, in which the only case of hypotony maculopathy occurred. There was a tendency of more eyes with lower IOP values in this group. The rate of loss of visual acuity of more than 2 lines was higher in group 2. Failures were more frequent in group 2 (7 of 24) compared with group 1 (1 of 24) ( P = 0.04, chi-square test). Conclusions To our knowledge, this is the first prospective, randomized clinical study to evaluate the efficacy of this different technique of mitomycin-C application. The postoperative application of mitomycin-C was effective, having few failures. This application of mitomycin-C may be associated with a lower rate of complications when used in eyes with complicated forms of glaucoma.