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Intraoperative mitomycin C 0.02% for pterygium: effect of duration of application on recurrence rate.

PURPOSE: To compare the effect of a 3- and 5-minute intraoperative application of topical mitomycin C 0.02% on the recurrence of pterygium. METHODS: A comparative, prospective clinical design was used. The study population consisted of 134 consecutive patients with unilateral primary advanced pterygium (growth of 3 mm or more horizontally from the limbus). All underwent excision of the lesion, leaving the sclera bare. At completion of surgery, topical mitomycin C 0.02% was applied for 3 minutes in the first 60 patients (group A) and for 5 minutes in the remaining 74 patients (group B). The patients were followed for 26 months by slit-lamp biomicroscopic examination of the anterior segment. Recurrent pterygium was defined as the postoperative appearance of a fibrovascular tissue crossing the limbus. RESULTS: After 12 months of follow-up, pterygium recurred in 20 patients (33.3%) in group A and in two patients (2.7%) in group B. After 15 months, the recurrence rates were 36.6% and 5.4%, respectively, and remained unchanged at 26 months. There were no cases of drug toxicity in either group. CONCLUSIONS: Five-minute intraoperative application of a single dose of 0.02% mitomycin C is safe and more effective than a 3-minute application in recurrence of pterygium.

Adult↗

Combined mitomycin C application and free flap conjunctival autograft in pterygium surgery.

PURPOSE: To evaluate the long-term postoperative outcome and complication rate of combined intraoperative low-dose mitomycin C application and free conjunctival autograft for the treatment of pterygium. METHODS: In a prospective, consecutive, noncomparative case series, a series of 46 consecutive patients (50 eyes) with primary pterygium (43 eyes) or recurrent pterygium (7 eyes) were studied. The patients' ages ranged from 23.0 to 80.0 years (mean, 53.4 years). All patients underwent pterygium excision combined with intraoperative low-dose mitomycin C application (0.02% for 2 minutes) and free conjunctival autograft. The mean follow-up period was 29.2 months (range 12 to 41 months). The main outcome measures were recurrence of pterygium and postoperative complications. RESULTS: Pterygium recurred to a small extent (0.5 mm) in one eye (2%) of a patient with recurrent pterygium. There were no intraoperative complications. Subconjunctival graft hematoma appeared soon after surgery and resolved spontaneously in five eyes (10%). One eye developed transient high intraocular pressure without optic nerve or visual field defect, and one eye developed mild symblepharon. There were no sight-threatening complications or serious side effects. CONCLUSIONS: By applying a single low dose of mitomycin C combined with free conjunctival autograft during pterygium excision, the recurrence rate of pterygium can be markedly reduced.

Adult↗

The effect of mitomycin-C on the biodistribution of 99Tcm-MDP in Balb/c mice.

Drug therapy can alter the biodistribution of radiopharmaceuticals. We studied the effect of mitomycin-C, a drug used in oncology, on the biodistribution in mice of 99Tcm-methylene diphosphonic acid (99Tcm-MDP). Three doses of mitomycin-C were administered. After the last dose, 99Tcm-MDP was injected and the animals were killed. The organs were isolated, their weight determined and the percent per gram injected dose (%ID/g) calculated. The %ID/g had increased in the pancreas, ovary, stomach, uterus, kidneys, spleen, thymus, heart, liver and lungs, but did not change significantly in thyroid, bone or brain. As a change in 99Tcm-MDP uptake by bone is not observed, a modification to bone scintigraphy is not required. As mitomycin-C treatment altered 99Tcm-MDP uptake in some organs, any hot spots should be evaluated carefully to avoid a misdiagnosis.

Animals↗

Late-onset blebitis/endophthalmitis: incidence and outcomes with mitomycin C.

PURPOSE: To assess the outcomes of patients who had late infections after undergoing filtering surgery with mitomycin C with respect to treatment, resultant vision, and maintenance of intraocular pressure. METHODS: A retrospective review of 233 eyes that underwent trabeculectomy with mitomycin C with or without coincident cataract extraction and intraocular lens insertion from August 1993 to June 1997 was undertaken. Records were examined for postoperative infection occurring at least 6 months after filtering surgery. Age, sex, date, and type of surgery were reviewed and entered into a computerized database. RESULTS: Bleb infections occurred in 6 of 233 (2.6%) eyes that underwent mitomycin C filtering surgery. Four of these developed endophthalmitis. The average postoperative time until infection was 24.7 months. Two patients had bleb leaks, one of which progressed to endophthalmitis. On resolution of infection, all blebs remained functional, and vision returned to preblebitis acuities in 67%. CONCLUSION: Aggressive topical antibiotic therapy with daily observation may be appropriate in selected cases of late-onset blebitis and endophthalmitis. Eyes may continue to have good visual outcomes and functioning filters without need for additional surgery or hospitalization. Early recognition and appropriate management of infections may play a role in these outcomes.

Aged↗

Conjunctival dysfunction and mitomycin C-induced hypotony.

PURPOSE: To determine the role of a physically intact conjunctiva in the development of chronic hypotony after mitomycin C-enhanced trabeculectomy. METHOD: Three patients with mitomycin C-related hypotonic maculopathy, but without a leak on Siedel test, had a thorough evaluation of the bleb area and an anterior segment fluorescein angiography. The bleb was excised and a pedicle flap, rotated from the temporal conjunctiva, was sutured to cover the defect superiorly. The scleral flap and its sutures were not disturbed. The excised bleb was subjected to light and electron microscopy. RESULTS: The Seidel test result was negative in all patients, but late phases of the anterior segment angiography showed a generalized seepage of aqueous from the bleb. After revision of the bleb, there was a gradual increase in the intraocular pressure, a reversal of the hypotonic maculopathy, and consequent improvement in visual acuity in all three patients, stable up to a minimum follow-up of 18 months. On histopathologic examination, the basement membrane was thickest under thin areas of the epithelium and thinnest below thicker epithelial layers. CONCLUSION: A dysfunctional conjunctival barrier, as evidenced by the "sweating" of the bleb and histopathologic alterations in the epithelial barrier, could be responsible for the hypotonic maculopathy in these patients. Excision of the conjunctiva alone and replacement by a pedicle conjunctival graft offers a safe and effective method of treating chronic hypotony after mitomycin C-augmented trabeculectomy in such patients.

Adolescent↗

Combined Baerveldt glaucoma drainage implant and trabeculectomy with mitomycin C for refractory glaucoma.

PURPOSE: To describe the surgical technique and clinical outcomes of a procedure for refractory glaucoma, concurrent Baerveldt glaucoma implant (BGI) and trabeculectomy with mitomycin C. MATERIALS AND METHODS: Medical records of all patients who underwent combined Prolene-ligated BGI and trabeculectomy with mitomycin C were retrospectively reviewed. Main outcome measures were intraocular pressure (IOP), number of glaucoma medications, visual acuity, and complications. Kaplan-Meier survival analysis was used to determine success, defined as IOP < 22 mm Hg, no reoperation for glaucoma, and no loss of light perception vision. RESULTS: The mean +/- SD follow-up period for 38 eyes of 36 patients was 34 +/- 36 months (range, 3-121 months), during which 18 of 38 eyes (47%) required laser suture lysis of the Prolene suture. Intraocular pressure was reduced from a mean (+/- SD) preoperative value of 35.7 +/- 12.8 to 12.7 +/- 4.7 mm Hg at 1-year follow-up and 11.9 +/- 5.5 mm Hg at the last follow-up visit ( < 0.001). Number of medicines used for glaucoma was reduced from a mean +/- SD preoperative value of 2.5 +/- 0.9 to 0.5 +/- 0.6 at 1-year follow-up and 0.6 +/- 0.8 at the last follow-up visit ( < 0.001). LogMar visual acuity remained stable at mean of 1.15 +/- 0.85 preoperatively, compared with 1.14 +/- 1.05 at 1-year follow-up, but declined to 1.61 +/- 1.01 at the last follow-up visit, a loss of an average of four lines of vision ( = 0.004). Cumulative success was 91% at year 1, 86% at year 2, and 81% at year 3. Three eyes (8%) had suprachoroidal hemorrhages, one eye (3%) needed reoperation for an extruded implant, one (3%) eye had poor vision due to chronic hypotony, three eyes (8%) required additional glaucoma surgery during the postoperative period, and one eye (3%) needed revision of the implant for pressure control. CONCLUSIONS: Combined BGI and mitomycin C trabeculectomy provides excellent postoperative IOP control in patients with refractory glaucoma.

Adult↗

The effects of hyaluronic acid, epidermal growth factor, and mitomycin in an experimental model of acute traumatic tympanic membrane perforation.

HYPOTHESIS: The goal of this study was to evaluate the effects of hyaluronic acid, epidermal growth factor, and mitomycin C on the healing of acute experimental traumatic perforations of the tympanic membrane. BACKGROUND: Most acute perforations of the tympanic membrane heal spontaneously. However, some form of surgical treatment (i.e., myringoplasty) is needed for nonhealing perforations. Because the closure occurs by squamous epithelial migration, drugs that stimulate this regenerative process may aid in the closure of the perforation, obviating the need for more extensive treatments. METHODS: Bilateral perforations of the tympanic membrane were created in 30 rats, divided into three groups (A, B, C). The perforations in the right ears were treated with hyaluronic acid, epidermal growth factor, or mitomycin C. Those in the left ears were left untreated for comparison. To examine the healing process in different periods, 5 animals were killed in each group at days 3, 5, 7, 9 and 14. The other 5 animals in each group were observed daily to determine the duration of perforation closures. Thirty surgical specimens (5 right sides from each group and all 15 left sides in all groups) were histopathologically examined for tympanic membrane thickness, fibroblastic reaction, neovascularization, and crust morphology. RESULTS: Hyaluronic acid and epidermal growth factor applications significantly shortened the healing in acute experimental traumatic perforations of the tympanic membrane (p = 0.0432); however, the difference between them was not significant (p = 0.3160). On the other side, tympanic membrane perforations treated with topical mitomycin C showed no evidence of closure. There were no significant differences in the histologic parameters between the treated groups and their contralateral control ears. CONCLUSION: Hyaluronic acid and epidermal growth factor accelerated the closure of acute tympanic membrane perforations in rats. This may make them clinically useful in augmenting the efficiency of conservative treatments of acute perforations of the tympanic membrane.

Adjuvants, Immunologic↗

Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106).

OBJECTIVE: The aim of this study was to evaluate the activity and toxicity of a combination regimen of CPT-11 and mitomycin-c as second-line chemotherapy for pretreated patients with advanced, metastatic, or both, gastric adenocarcinoma. MATERIALS AND METHODS: Patients with pretreated metastatic disease or early relapsed after adjuvant chemotherapy were enrolled. Entry criteria included histologic/cytologic diagnosis of gastric adenocarcinoma, age 18 to 75 years, performance status > or =70 (Karnofsky scale), bi-dimensionally measurable disease. Patients received CPT-11 and mitomycin-c at the dosage of 150 mg/m2 on days 1 and 15, and 8 mg/m2 on day 1, respectively, every 4 weeks. The disease evaluation was done every 3 cycles. RESULTS: Among the 38 patients we observed, 1 (3%) complete response and 11 (29%) partial responses for an overall response rate of 32% according to an intent-to-treat analysis. The median duration of response was 6.5 months. The median time to progression was 4 months with a median overall survival 8 months. All patients were evaluable for toxicity and the only grade 3-4 observed toxicities were leukopenia (8%), neutropenia (21%), and anemia (5%). CONCLUSIONS: The combination of CPT-11 and mitomycin-c is an active and well tolerated second-line treatment in pretreated gastric cancer patients. Further studies are needed to test its role in first-line treatment.

Adenocarcinoma↗

Long-term results after bare sclera pterygium resection with excimer smoothing and local application of mitomycin C.

PURPOSE: To evaluate the long-term results and complications after bare sclera pterygium excision with local application of mitomycin C and consecutive smoothing of the wound area with an excimer laser (PTK). METHODS: This was an observational case series of 133 eyes of 101 patients who underwent pterygium surgery using the bare sclera technique. Thirty-one of these treated eyes (23%) were recurrences with a mean of 3 previous operations. After pterygium surgery, phototherapeutic keratectomy with an ArF:excimer laser was performed in the area of the excision. Additionally, all patients were treated with mitomycin C 0.02% twice daily for 4 days. Median follow-up was 53 months (minimum, 36). RESULTS: In the group with primary pterygia, 3 recurrences occurred after 6, 12, and 28 months (recurrence rate, 2.9%). In the group with previous pterygium operations, 2 recurrences (recurrence rate, 6.4%) were recorded. Uncorrected visual acuity of all treated patients improved from 0.61 preoperatively to 0.79 postoperatively (P < 0.0001), best corrected visual acuity increased from 0.82 to 0.91 (P = 0.0001) [LogMAR]. Mean astigmatism was significantly reduced from 1.54 D preoperatively to 0.61 D postoperatively (P < 0.0001). In 7 eyes, discrete granulomas developed postoperatively (5.3%); in 3 cases (2.3%), dellen formation occurred that persisted for a maximum of 4 months. No further complications were recorded during the follow-up. CONCLUSIONS: Pterygium excision using the bare sclera technique, phototherapeutic keratectomy, and local application of mitomycin C 0.02% eyedrops is a safe method with good functional results and a low recurrence rate.

Corneal Diseases↗

Treatment of cystic epithelial downgrowth with intralesional administration of mitomycin C.

PURPOSE: To report a case of postoperative cystic epithelial downgrowth treated with needle aspiration and intralesional administration of mitomycin C. METHODS: Case report. A 60-year-old woman with a history of right cataract surgery 7 years ago presented with decreased vision of 1/60. The reduced vision was diagnosed secondary to a large acquired cystic epithelial downgrowth on the surface of the iris occluding the pupil. RESULTS: The cystic epithelial downgrowth was treated with aspiration and intralesional administration of mitomycin C solution. There was no evidence of recurrence on follow-up 1 year after the procedure. CONCLUSIONS: Treatment of acquired cystic epithelial downgrowth with needle aspiration and intralesional administration of mitomycin C resulted in a satisfactory outcome without undertaking more extensive and invasive surgical treatments.

Antibiotics, Antineoplastic↗

Slit-lamp needle revision of failed filtering blebs using high-dose mitomycin C.

PURPOSE: To investigate the efficacy of bleb needle revision with high-dose mitomycin C in reviving failed filtering blebs after 1 year. PATIENTS AND METHODS: We reviewed the charts of 44 patients with one eye that had undergone bleb needle revision with a mixture of 0.1 mL of mitomycin (0.4 mg/mL) mixed with 0.1 mL of non-preserved 1% lidocaine. At least 12 months of follow-up were required. A successful bleb needle revision was defined as one that did not require a subsequent needling, glaucoma surgery, or medication to reach an intraocular pressure (IOP) greater than 4 mm Hg but less than 22 mm Hg. A qualified success was defined as a successful bleb needle revision that required subsequent needling or medication. RESULTS: The bleb needle revision with high-dose mitomycin was a success or qualified success after 12 months in 28 patients or 64% (95% confidence interval, 50% to 78%). The baseline IOP in these patients was 26.7 +/- 8.2 mm Hg (range 15 to 48 mm Hg) using an average of 1.5 +/- 1.5 glaucoma medications. The IOP after 1 year was 13.6 +/- 4.0 (range 6 to 21 mm Hg) with an average of 0.5 +/- 0.8 medications. Of 44 patients, 17 (39%) were successes and 11 (25%) were qualified successes. CONCLUSION: Bleb needle revision with high-dose MMC was effective in reducing the IOP in 64% of eyes with a failed filtering bleb with minimal long-term complications.

Adult↗

Outcomes of laser suture lysis after initial trabeculectomy with adjunctive mitomycin C.

PURPOSE: To evaluate and compare outcomes of eyes that underwent laser suture lysis (LSL) after initial trabeculectomy with mitomycin C (MMC) to those that did not require such an intervention. METHODS: We reviewed the charts of consecutive patients with open-angle glaucoma who underwent initial trabeculectomy with mitomycin C at the Jules Stein Eye Institute between 1998 and 2003. Primary outcome measures were intraocular pressure (IOP) control at 1 year and success rate of trabeculectomy according to following criteria: criteria A, IOP < 21 mm Hg with >or=20% IOP reduction and criteria B, IOP < 15 mm Hg with >or=30% IOP reduction. Kaplan-Meier survival analysis and Cox's proportional hazards regression analysis were used to estimate and determine influence of laser suture lysis on success rates after trabeculectomy. RESULTS: Laser suture lysis was performed in 95 eyes (84 patients) whereas 146 eyes (121 patients) did not require it. IOP was significantly higher at 12 months in laser suture lysis eyes compared with non-laser suture lysis eyes (12.9 +/- 5.2 mm Hg versus 11.0 +/- 4.1 mm Hg; P = 0.04). Laser suture lysis eyes also had decreased success rates with criteria B (57% compared with 73% at 1 year for non-LSL eyes; P = 0.005). However, only late laser suture lysis (last LSL session >10 days after trabeculectomy) was associated with worse outcome in Cox's proportional hazards model using criteria B (HR = 2.26; P = 0.004). Late hypotony occurred in 4% and 1% of non-LSL and LSL eyes, respectively. CONCLUSIONS: Eyes that undergo laser suture lysis >10 days after initial trabeculectomy with mitomycin C are more likely to have poorer long-term IOP control than eyes not requiring laser suture lysis or eyes undergoing laser suture lysis <or=10 days after surgery.

Aged↗

Successful treatment with mitomycin C eye drops for conjunctival diffuse intraepithelial neoplasia with sebaceous features.

Conjunctival biopsy specimens from the right eye of a 66-year-old woman who had a 10-year history of an irritated and swollen right upper eyelid were diagnosed as diffuse intraepithelial neoplasia with sebaceous features. The treatment consisted of two courses, 2 weeks apart, of 0.02% mitomycin C eye drops. Biopsies performed after completion the second course showed no evidence of neoplastic involvement. Severe trichiasis that developed after the biopsies was managed surgically. Today, 46 months after completion of mitomycin C treatment, the conjunctiva shows no inflammation, the eyelid is not swollen or irritated, and there is no clinical indication of recurrence. This case report demonstrates that conjunctival diffuse intraepithelial neoplasia of the conjunctiva with sebaceous features can be successfully treated by treatment with mitomycin C drops.

Aged↗

Radiofrequency myringotomy with the topical use of mitomycin C: an experimental study.

OBJECTIVE: To assess the use of radiofrequency myringotomy in combination with mitomycin C as an alternative myringotomy technique on rabbits. STUDY DESIGN: Experimental animal research protocol. SETTING: University of Crete, School of Medicine, Medical Experimental Education and Research Center. METHODS: Radiofrequency myringotomies were performed under general anesthesia on both ears of 20 rabbits. Mitomycin C (0.3 mg/ml) pledgets were applied in the right ears (study group) and saline pledgets in the left ears (control group). Animals were monitored using otomicroscopy weekly until myringotomy closure. Kaplan-Meier survival techniques were used to compare myringotomy patency time between the two sides. INTERVENTION: Radiofrequency myringotomy under general anesthesia on both ears of 20 rabbits. MAIN OUTCOME MEASURE: Myringotomy patency time. RESULTS: The mean patency time of the study group was 5.45 weeks (95% confidence interval, 5.185-5.715 weeks). The mean patency rate for the control side was 1.60 weeks (95% confidence interval, 1.38-1.82 weeks). The Breslow (generalized Wilcoxon) test showed the study group to have significantly longer patency of radiofrequency myringotomy than the control group (p<0.0001). CONCLUSION: The patency period of radiofrequency myringotomy was not long enough to be proposed as an alternative to the insertion of ventilation tubes, although mitomycin C had a significant adjunct effect in prolonging the patency rate of radiofrequency myringotomy on rabbits.

Administration, Topical↗

Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy.

BACKGROUND: Haemophilus aphrophilus is a rare cause of ocular infection. It has been reported once as a cause of late-onset endophthalmitis in a patient with an inadvertent bleb after cataract surgery. We present a case of Haemophilus aphrophilus bleb infection after a mitomycin trabeculectomy. METHODS: A 56-year-old woman presented with a bleb infection 10 weeks after a mitomycin C augmented trabeculectomy at a University tertiary referral practice of one of the authors (GET). The causative organism was Haemophilus aphrophilus, identified by the Toronto Public Health Laboratory, Ontario, Canada. RESULTS: The bleb infection resolved following topical, subconjunctival and intravenous antibiotic therapy. A formal bleb revision was required to repair a persistent bleb leak. CONCLUSION: Patients who have had trabeculectomies augmented with mitomycin C may be predisposed to bleb infection with unusual organisms. Prompt diagnosis and treatment is necessary to control the infection. Increased awareness and communication with laboratory personnel may increase the isolation of this fastidious organism.

Anti-Bacterial Agents↗

Use of topical mitomycin C in myoplasty of the medial rectus muscle of rabbits.

To possibly reduce postoperative adhesions that occur after ocular myoplasties, we investigated the topical effects of 0.04% mitomycin C on the repaired areas of the medial rectus muscle using an equine renal capsule preserved in 98% glycerin for reinforcement of the sutures. Twenty-four rabbits, divided into two groups of 12 animals each [untreated (control) and treated group (MMC)], were submitted to surgical rupture of the medial rectus muscle of one eye and repair of the defect 24 h later with sutures and an equine renal capsule. Post-operative prophylactic treatment of the two groups consisted of the administration of eye drops containing neomycin, polymyxin B and dexamethasone at regular 6-h intervals for eight consecutive days and daily rinsing with physiological saline. MMC animals received additional treatment with topical 0.04% mitomycin C every 6 h for 14 consecutive days. Slit lamp biomicroscopy showed greater irritation of the ocular surface in MMC animals during the first days post operatively. Adhesions were observed at 15 and 30 days of assessment in the two groups, but were more extensive in control animals at 60 days. Histopathology revealed inflammatory exudation in both groups, which was greater in MMC animals. Mitomycin C (0.04%) instilled at 6-h intervals for 14 consecutive days reduced the occurrence of fibrosis in the myoplastic areas. However, the equine renal capsule was found to be of little benefit for the reinforcement of myoplasties.

Administration, Topical↗

A phase-1 study of sequential mitomycin C and 5-aminolaevulinic acid-mediated photodynamic therapy in recurrent superficial bladder carcinoma.

OBJECTIVE: To report a phase-1 study of patients with recurrent superficial bladder cancer treated with photodynamic therapy (PDT) using sequential mitomycin C and 5-aminolaevulinic acid (ALA). PATIENTS AND METHODS: Twenty-four patients were treated, the primary endpoint being the safety and tolerability of combined therapy at increasing doses of ALA and light. RESULTS: Mitomycin C instillation was followed by ALA concentrations of 6%, 8% or 10%; there was no effect on toxicity. The light dose, at a wavelength of 635 nm, was increased from zero to 25 J/cm(2), with the upper fluences producing transient symptoms. There were no episodes of skin photosensitivity or systemic toxicity. A total fluence of 25 J/cm(2) represented the upper light dose for the tolerability of this procedure by patients. There were no persistently high urinary symptom scores or reduction in functional bladder capacity up to > or =24 months of follow-up. In this group, cumulative tumour recurrences were none at 4, two at 8, six at 12, nine at 18 and 11 at 24 months after PDT, respectively. CONCLUSION: Sequential mitomycin C and ALA-PDT is a safe and well tolerated treatment, with potential for managing difficult-to-control superficial transitional cell carcinoma and carcinoma in situ of the bladder.

Aged↗

Systemic allergic contact dermatitis from intravesical instillation of the antitumor antibiotic mitomycin C.

6 cases of contact allergy to the antitumor antibiotic mitomycin C from intravesical instillation are described. Reports suggest that up to 9% of patients treated with mitomycin C for chemoresection/prevention of superficial bladder cancer will develop cutaneous side-effects. Patients may present either with vesicular dermatitis of the hands and feet and/or dermatitis of the genitals, or with more widespread eruptions. Probably most, if not all, skin reactions are caused by contact allergy. The distribution is suggestive of systemic contact dermatitis from mitomycin C absorbed from the vesical mucosa.

Administration, Intravesical↗