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Intraoperative mitomycin C in the treatment of cicatricial obliterations of conjunctival fornices.

PURPOSE: To investigate whether the intraoperative use of topical mitomycin C improved the postoperative outcome in cases of cicatricial obliteration of conjunctival fornices. METHODS: Ten eyes of five patients were subjected to surgical lysis of the synechiae followed by intraoperative application of 0.4 mg mitomycin C per milliliter of saline for 3 to 5 minutes. RESULTS: After a follow-up period of 12 to 19 months, no recurrence of synechiae was observed, the conjunctival fornices remained open, and conjunctival overgrowths on the cornea did not recur. No adverse effect was observed. CONCLUSION: Intraoperative application of mitomycin C proved useful in the surgical treatment of cicatricial shrinkage of conjunctival fornices.

Administration, Topical↗

Treatment of recurrent conjunctival epithelial neoplasia with topical mitomycin C.

PURPOSE: To study the effect of topical mitomycin C on conjunctival squamous neoplasia. METHODS: Three patients with recurrent conjunctival epithelial neoplasia were treated with topical mitomycin C 0.04%. RESULTS: Six to 9 months after treatment, no patient had clinical evidence of tumor recurrence. Conjunctival biopsy in two patients and cytology in one patient showed no evidence of tumor 1 to 4 months after treatment. One patient required short-term treatment for corneal edema and epithelial toxicity. CONCLUSION: Topical mitomycin C caused tumor regression without recurrence for 6 to 9 months after treatment.

Administration, Topical↗

Mitomycin C therapy for corneal intraepithelial neoplasia.

We treated three patients who had intraepithelial neoplasia involving the visual axis and a subsequent decrease of visual acuity with topical mitomycin C 0.02% four times daily for ten to 22 days. In two of the three cases, the intraepithelial neoplasia was histologically confirmed. The intraepithelial neoplastic lesion was replaced by biomicroscopically normal epithelium within nine weeks of the beginning of drug administration and did not recur during the four to 12 months of follow-up. Adverse reactions to topical mitomycin in two patients ranged from minimal conjunctival hyperemia after 14 days to marked hyperemia, ocular pain, and blepharospasm after 22 days. These signs and the symptoms, however, disappeared after the drug was discontinued. Administration of topical mitomycin C 0.02% for two weeks may be an effective treatment for corneal intraepithelial neoplasia that affects the visual axis.

Administration, Topical↗

Combined phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy with mitomycin C.

PURPOSE: We evaluated the effectiveness of combined phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy with mitomycin C in patients with coexisting cataract and glaucoma. METHODS: We conducted a retrospective review of the records of 21 consecutive patients who had combined phacoemulsification, posterior chamber intraocular lens implantation, and trabeculectomy with mitomycin C. Patients were selected for the combined procedure on the basis of the degree to which intraocular pressure was controlled, toleration of medical therapy, degree of glaucomatous optic nerve damage, and extent of visual impairment because of cataract. Nine (43%) of the 21 patients had previous incisional surgery and were at high risk of surgical failure. All patients had at least six months' follow-up. Sixteen (76%) of 21 patients had at least one year of follow-up. RESULTS: The mean preoperative intraocular pressure was 20.8 +/- 5.0 mm Hg (range, 13 to 35 mm Hg), which decreased to a mean postoperative intraocular pressure of 15.1 +/- 3.1 mm Hg (range, 9 to 21 mm Hg) as measured at last follow-up (P = .0002). The intraocular pressure was controlled between 6 and 21 mm Hg) in all patients at last follow-up. Seventeen (81%) of 21 patients had a best-corrected visual acuity of 20/40 or better at last follow-up. No patient had a decrease in visual acuity after surgery. Fifteen (71%) of 21 patients were using no antiglaucoma medications at last follow-up. Four of the remaining six patients were using one medication, and two were using two medications. A hyphema (less than 1.0 mm) was seen in seven (33%) of 21 patients and was the most common postoperative complication. No patient had a postoperative wound or bleb leak or a shallow anterior chamber. No patient developed symptomatic hypotony. CONCLUSIONS: The glaucoma triple procedure with adjunctive mitomycin C appears to be a safe and effective surgical technique for treating selected patients with coexisting cataract and glaucoma.

Adult↗

Mitomycin C trabeculectomy in eyes with cicatricial conjunctiva.

PURPOSE: To demonstrate favorable outcome of mitomycin C-augmented trabeculectomy in eyes with broad cicatricial conjunctiva created by previous surgeries. METHODS: Forty-six eyes (40 patients) with extensive conjunctival scarring that had undergone mitomycin C trabeculectomy were reviewed retrospectively. RESULTS: After a mean follow-up +/- SD of 13.7 +/- 7.8 months (range, 6 to 36 months), intraocular pressure was well controlled, below or equal to 16 mm Hg and 21 mm Hg, respectively, in 33 (72%) and 44 (96%) of the 46 eyes. In all eyes, a functional filtering bleb was present during the follow-up periods. CONCLUSION: Mitomycin C trabeculectomy after dissection of conjunctival scar tissue may be useful for treating refractory glaucoma.

Adult↗

Trabeculectomy with adjunctive mitomycin C in pediatric glaucoma.

PURPOSE: To determine the safety and efficacy of trabeculectomy with adjunctive mitomycin C in patients 17 years of age or younger, and to identify risk factors for failure of this surgical technique. METHODS: Retrospective review of consecutive cases of pediatric glaucoma that underwent mitomycin C augmented trabeculectomy between January 1991 and December 1995. Forty-nine patients (60 eyes) with a mean age of 7.6 years (range, 6 weeks to 17.6 years) were identified and followed up until repeat glaucoma surgery, or after a minimum of 6 months. Success was defined as intraocular pressure control of 22 mm Hg or less with or without topical glaucoma control medication, no evidence of glaucoma progression, no further glaucoma surgery necessary, and no visually devastating complication. RESULTS: Cumulative probabilities of success +/- SD for 49 eyes (one eye per patient) were 67% +/- 13% at 12 months and 59% +/- 15% at 24 months. Multivariate regression analysis yielded the following characteristics as significantly increased risk for failure: age of less than 1 year at time of surgery (risk ratio, 5.6; confidence interval, 2.1 to 14.7; P = .0005), and aphakia (risk ratio, 2.7; confidence interval, 1.1 to 6.9; P = .0364). Shallow anterior chamber (17 [28%] of 60 eyes) and serous choroidal detachment (13 [22%] of 60 eyes) were the most common complications. Four (11%) of 38 eyes with obtainable Snellen acuity were noted to have a decrease in best-corrected visual acuity of more than 2 Snellen lines or loss of light perception. In 5 (8%) of 60 eyes bleb-related endophthalmitis was noted. CONCLUSIONS: Trabeculectomy with adjunctive mitomycin C is generally effective for the treatment of pediatric glaucoma, especially in phakic children over 1 year of age. However, late-onset bleb-related endophthalmitis is a substantial risk in this patient population.

Adolescent↗

Treatment of recurrent conjunctival papillomatosis with mitomycin C.

PURPOSE: To report an effective treatment for recurrent squamous papillomas of the conjunctiva with excision and application of mitomycin C. METHOD: Case report. RESULTS: A 5-year-old African-American girl with recurrent squamous papillomas of the right bulbar and palpebral conjunctiva was treated with multiple therapies, including excision, cryotherapy, and conjunctival injection of alpha-interferon; all therapies were followed by recurrence. After treatment with excision followed by intraoperative application of mitomycin C to the involved conjunctiva, the patient had no recurrence in a 30-month period. CONCLUSIONS: Excision with application of mitomycin C was successful in managing a case of squamous papillomatosis that was resistant to traditional therapy.

Antibiotics, Antineoplastic↗

[Mitomycin C: prevention and treatment of anterior glottic synechia].

OBJECTIVES: Topical applications of mitomycin C to the anterior glottis may prevent anterior glottic synechia (prevention group) or restenosis (treatment group). METHODS: In the prevention group, six patients with glottic carcinoma involving the anterior commissure were treated by transoral laser surgery. Repeated procedures were performed in one patient. For the six patients in the treatment group, the anterior glottic synechia was secondary to frontolateral laryngectomy (three patients), transoral laser therapy for laryngeal papillomatosis (two patients) or bilateral glottic carcinoma (one patient). Mitomycin C (0.4 mg/ml) was used as a topical application on the anterior commissure for a duration of 4 minutes. Outcome was assessed clinically at three months using a visual scale: no synechia (success), micro-synechia (partial failure), and synechia (failure). RESULTS: In the prevention group, there were six successes and one partial failure. In the treatment group, there were two successes, three partial failures, and one failure. No side effects were noted. CONCLUSION: Topical application of mitomycin C was effective to prevent anterior glottic synechia after transoral laser surgery for glottic carcinoma involving the anterior commissure. It is an alternative to endolaryngeal keel in patients with sequellar synechia. These preliminary results should be further evaluated in a larger series.

Adult↗

Mitomycin C primary trabeculectomy with releasable sutures in primary glaucoma.

PURPOSE: To evaluate the effects of mitomycin C and a releasable suture technique on outcomes of primary trabeculectomy in primary glaucoma patients. METHODS: A prospective analysis of patients who underwent primary trabeculectomy with a mitomycin C concentration of 0.2 mg/mL for 2 minutes. For closing the scleral flap, releasable sutures were used in 18 patients (17 eyes), Group 1, or permanent sutures in 18 patients (20 eyes), Group 2. Clinical outcome factors including postoperative intraocular pressure (IOP), visual acuity, and incidence of complications were determined. RESULTS: The mean follow-up periods were 8.1 +/- 1.3 months in Group 1 and 8.3 +/- 1.3 months in Group 2. The postoperative reduction in IOP was highly significant (P <.0001) at all time intervals in both groups. In all measurement of IOP before the second week, mean IOP in Group 2 was found significantly lower than the mean IOP in Group 1 (P =.01). No statistically significant differences were found between the groups at later mean IOP measurements. At the last visit, the complete success rate was 88.8% in Group 1 and 85.0% in Group 2. No serious complications such as hypotonous maculopathy were observed in any patient. CONCLUSION: Primary trabeculectomy with mitomycin C in eyes with primary glaucoma showed effective IOP pressure reduction. There were no cases of serious complications. In the early postoperative period IOP was controlled better in the releasable suture group.

Adult↗

Mitomycin C in combination with orchiectomy for newly diagnosed metastatic prostate cancer: preliminary results on a randomized trial.

The preliminary results of a randomized trial comparing orchiectomy versus orchiectomy and mitomycin C in 119 newly diagnosed metastatic prostate cancer patients are presented. Of 109 evaluable patients 57 were treated with orchiectomy alone and 52 received adjuvant intravenous mitomycin C. Mean interval to progression was 13 months in the orchiectomy group versus 11 months in the mitomycin C group. Preliminary analysis did not demonstrate a favorable effect of the combination with this chemotherapeutic agent compared to orchiectomy alone (p = 0.3).

Aged↗

Phase II study of interferon-alpha and chemotherapy (5-fluorouracil and mitomycin C) in metastatic renal cell cancer.

A total of 49 patients with metastatic renal cell cancer underwent recombinant interferon-alpha 2a therapy combined with chemotherapy. Before therapy the patients without nephrectomy underwent angioinfarction of the primary renal tumor. Combined treatment included interferon at 5 x 10(6) units per m.2 intramuscularly daily, 5-fluorouracil at 750 mg./m.2 daily by continuous infusion intravenously (days 1 to 5) and mitomycin C at 5 mg./m.2 per day intravenously (days 1 and 2) repeated every 28 days. Of the patients 17 (35%, 95% confidence interval 22 to 49%) responded, and all 17 had partial remission that lasted a median of 7.1 months (range 4.2 to 20.9+ months). Response rate differed by metastatic sites: lung 46% (18 of 39 patients), lymph nodes 46% (6 of 13), mediastinum 20% (2 of 10) and liver 18% (2 of 11). Grade 3 to 4 toxicity (World Health Organization) included neutropenia (79% of the patients), thrombocytopenia (45%), stomatitis (34%), diarrhea (8%), nausea (18%) and central nervous system disorders (18%). The overall 35% response rate suggests that the combination of interferon-alpha 2a, 5-fluorouracil and mitomycin C is synergistic. Future studies are needed to confirm this finding and to assess the role of mitomycin C.

Antineoplastic Combined Chemotherapy Protocols↗

Intravesical bacillus Calmette-Guerin or mitomycin C in the treatment of carcinoma in situ of the bladder following prior pelvic radiation therapy.

A total of 20 patients received intravesical bacillus Calmette-Guerin (BCG) or mitomycin C for the treatment of carcinoma in situ following previous pelvic radiation therapy. Of the patients 14 (70%) responded completely after 1 or 2 courses of intravesical therapy. Mean followup from diagnosis of carcinoma in situ currently is 15.7 months. Complications of BCG and mitomycin C therapy were compared to the established complications of intravesical therapy with these agents. The incidences of fever greater than 103F, hematuria and bladder contracture were increased in patients receiving BCG following radiation therapy, although the cause of bladder contracture was probably multifactorial in our patient population. Our data suggest that BCG and mitomycin C are safe and biologically effective agents for the intravesical treatment of carcinoma in situ after pelvic radiation therapy.

Administration, Intravesical↗

Mitomycin C bladder instillation therapy for bladder tumors.

Patients with bladder tumors underwent a course of topical bladder instillation of 20 mg. mitomycin C in 20 ml. sterilized distilled water 3 times weekly for a total of 20 procedures. In 22 of the 50 patients (44 per cent) the tumors disappeared completely, while in 16 patients (32 per cent) there was partial disappearance and in 12 patients (24 per cent) there was no affect. Therefore, the total effective rate was 76 per cent. We concluded from our studies that mitomycin C topical therapy could be applied to low stage and low grade bladder tumors less than 1 cm. in diameter, without regard to the number of tumors. We now use mitomycin C topical therapy in all cases of bladder tumors. Local bladder reaction was noted in 3 cases but a complete course of therapy was accomplished in each case--in 2 cases without interruption of treatment and in 1 case by delaying treatment for 1 week. Abnormal values of hematocrit, white blood cells and platelets in blood were not observed during therapy.

Administration, Topical↗

Metabolic activation of mitomycin C by NADPH-ferredoxin reductase in vitro.

Mammalian NADPH-ferredoxin reductase (EC 1.18.1.2) functions in the mitochondrial electron transport chain for cytochrome P-450-dependent steroid hydroxylation. Significant homology of three-dimensional structure exists in the surroundings of FAD between NADPH-ferredoxin reductase and NADH-cytochrome b5 reductase. The latter is involved in the bioreduction of mitomycin C (MC), a prototype antitumor agent. In this study, we assessed the capacity of NADPH-ferredoxin reductase to activate MC. Mitomycin C increased the NADPH oxidase activity of NADPH-ferredoxin reductase. In the absence of ferredoxin, the Km value of NADPH-ferredoxin reductase for MC was 73.5 +/- 2.3 microM. While in the presence of 500 nM ferredoxin, a Lineweaver-Burk plot exhibited a biphasic curve. NADPH-ferredoxin reductase-mediated reduction of MC resulted in the formation of an alkylated complex of 4-(p-nitrobenzyl) pyridine and an increase in plasmide DNA single-strand breaks under hypoxic conditions. With the addition of 500 nM ferredoxin, the amount of the alkylated complex of 4-(p-nitrobenzyl) pyridine and the plasmide DNA single-strand breaks increased by 40% and 37%, respectively. However, neither alkylated complex of 4-(p-nitrobenzyl) pyridine nor DNA strand breaks was observed in the presence of SOD and catalase under aerobic conditions. These findings demonstrate that NADPH-ferredoxin reductase is capable of catalyzing the bioactivation of mitomycin C under hypoxic conditions in vitro.

Alkylation↗

Bladder wall fibrosis following intravesical mitomycin treatment for superficial bladder cancer.

Mitomycin is used extensively for the prevention of recurrence of superficial bladder cancer. Most treatment regimens of mitomycin are long term, since this seems more effective in preventing recurrence. During treatment some patients develop cystitis of variable severity, which may lead to mucosal ulcerations and cessation of treatment. We report a case in which long-term treatment with mitomycin, following a single episode of transitional cell bladder cancer, has led to bladder fibrosis and loss of its function, without evidence of tumor recurrence.

Administration, Intravesical↗

Efficacy of probing the nasolacrimal duct with adjunctive Mitomycin-C for epiphora in adults.

PURPOSE: To investigate the efficacy and safety of adjunctive low-dose mitomycin-C during lacrimal probing for adults with blocked nasolacrimal ducts. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: From January 1998 to December 2000, a total of 32 adult patients (36 eyes) seen with epiphora caused by primary nasolacrimal duct obstruction was treated and evaluated. INTERVENTION: Lacrimal probing with adjunctive mitomycin-C (0.2 mg/ml). MAIN OUTCOME MEASURES: Objective evaluation of patency with irrigation, as well as patients' subjective assessment of improvement. RESULTS: For 32 of the treated eyes (89%), the nasolacrimal duct remained open 9 months after treatment. Repeat procedure was successful for two of the remaining four eyes with recurrent obstruction during follow-up, yielding an overall patency rate of 94%. Patient satisfaction was assessed after 9 months and indicated that the epiphora was at least mildly improved for 30 (83%) of the treated eyes. Watering was completely absent for nine eyes (25%), rated as moderately improved for 17 (47%), and mildly improved for 4 (11%). No complications were encountered over the 9-month follow-up period. CONCLUSIONS: Our experience suggests good long-term results for probing with adjunctive, topical Mitomycin-C for cases of adult epiphora caused by obstruction of the nasolacrimal duct followed by repeat procedure if necessary. It can be recommended as a simple, effective, and minimally invasive technique, with no significant complications resulting from low-dose use in our study.

Aged↗

Topical mitomycin-C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma.

PURPOSE: To evaluate the efficacy of topical mitomycin-C for pagetoid invasion of the conjunctiva by sebaceous gland carcinoma. DESIGN: Prospective noncomparative consecutive interventional case series. INTERVENTION: All patients received topical 0.04% mitomycin-C four times daily for 1 week followed by 1 week off medication. The treatment cycles were repeated until resolution of the conjunctival malignancy was clinically evident. PARTICIPANTS: Four patients with histopathologically proven intraepithelial (pagetoid) invasion of the conjunctiva by sebaceous gland carcinoma were managed with this regimen. RESULTS: The mean patient age was 78 years. Before treatment, the main tumor site included the upper eyelid in two cases and the lower eyelid in two cases. Previous resection of the tumor had been performed elsewhere in three cases over the prior 6 years. At the time of our examination, map biopsies confirmed pagetoid invasion involving 25% to 90% of the conjunctival surface, with bulbar, forniceal, and tarsal conjunctival involvement in all four cases and corneal extension in one case. There was no evidence of deep tumor within the conjunctival stroma or tarsus in any case. After treatment, medication intolerance and early discontinuation occurred in one patient, and continued tumor progression was documented. Of the remaining three patients, chemotherapy was used for a mean of four cycles with complete resolution of the pagetoid invasion, confirmed histopathologically in two cases, and without recurrence in all three cases over 12 months (mean) follow-up. The medication caused moderate temporary local irritation but no serious intraocular or extraocular complications. CONCLUSIONS: Preliminary evidence suggests that topical mitomycin-C is effective treatment for pagetoid invasion of the conjunctiva by sebaceous gland carcinoma. Longer follow-up is necessary to assess the duration of tumor control.

Adenocarcinoma, Sebaceous↗

Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil.

PURPOSE: The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea. METHODS: Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU. RESULTS: Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing. CONCLUSION: These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.

Animals↗