Mitomycin-C induced improvement in superficial bladder tumors: A morphologic and immunohistochemical evaluation

Summary Twenty bladder biopsies from ten patients with superficial transitional cell carcinoma were obtained prior to and following therapy with intravesical mitomycin-C. Each biopsy was evaluated histologically and immunohistochemically for A, B, H blood group antigen (BGA) expression. A, B and H blood group antigens were identified using monoclonal anti-A, B and H antibody and were localized with the avidin-biotin-peroxidase complex (ABC) technique. Particular attention was directed toward flat urothelial lesions and the urothelium adjacent to papillary tumors. Routine histologic evaluation showed improvement in posttherapy biopsies compared to corresponding pre-therapy biopsies in 7/10 cases but was equivocal in 3/10 cases. Immunohistochemical evaluation, however, showed improvement in all 10 cases, as judged by increased urothelial BGA expression. This increase in urothelial BGA expression after intravesical mitomycin-C therapy suggests a therapy induced improvement in dysplastic urothelium which was not uniformly evident on routine histologic examination.Presented in part at the 73rd Annual Meeting of International Academy of Pathology, March 1984, San Francisco, California, USA     

Interaction between gemcitabine and mitomycin-C in vitro

Both gemcitabine (2′,2′-difluorodeoxycytidine; dFdCyd) and mitomycin-C (MMC) are active against several solid malignancies. dFdCyd is an attractive agent for use in combination with drugs which damage DNA and with radiation therapy because of its ability to inhibit DNA replication and repair as well as its radiosensitizing effect. We hypothesized that the repair of MMC adducts in DNA might be inhibited by dFdCyd leading to a synergistic effect. To test this possibility, we studied the effect of combining dFdCyd and MMC in HT29 human colon carcinoma cells in vitro. The cells were exposed to a variety of drug concentration ratios and schedules, then assessed for clonogenic survival. D₅₀ values (drug concentration at which clonogenicity is inhibited by 50%) were calculated, and the interactive effects of the two drugs were evaluated using median effect analysis. In this approach, if the calculated combination index (CI) is <1, 1, or >1, it indicates synergism, additivity, or antagonism, respectively (Chou and Talalay 1984). We found that marked synergy (CI of 0.5–0.7) was produced by concurrent exposure to mitomycin and gemcitabine. In contrast, sequential treatment led only to additivity. These findings suggest that, when combined in an appropriate schedule, the chemosensitizing effect of gemcitabine may be beneficial in the treatment of malignancies which are sensitive to MMC. Received: 19 November 1998 / Accepted: 21 June 1999     

Preservation of Function and Histologic Appearance in the Injured Glottis With Topical Mitomycin-C

Objective: To evaluate the functional and histological effects of a single application of topical mitomycin-C after laser injury in the posterior canine glottis. Study Design: A prospective, randomized study of 16 canines. Methods: A supersaturated (1%) solution of topical mitomycin-C was applied to a unilateral, laser-induced injury near the cricoarytenoid joint in eight dogs. The mitomycin-soaked pledget was placed immediately after induction of the injury and was left in contact with exposed cartilage for 3 minutes. The opposite side was not injured to provide an internal control. In eight additional dogs, the same laser injury was allowed to heal untreated. After 6 weeks, the animals were sacrificed and their larynges harvested. Arytenoid adduction sutures were placed bilaterally, and the force required to bring the vocal folds to midline was measured for each side using tensiometry. Gross and microscopic histological analysis was performed. Statistical analysis was accomplished using a two-tailed Student t test of unpaired samples, and the Wilcoxon Signed Rank Test where appropriate. Results: The mitomycin-C treated larynges demonstrated improved cricoarytenoid joint mobility (P = .007), decreased granulation tissue development (P = .03), and complete prevention of secondary “vocal granuloma” formation (P = .0004) when compared with eight dogs with identical laser injuries allowed to heal untreated. No complications were noted. Conclusions: This study demonstrates functional preservation and improved histological appearance of the injured glottis after a single treatment with topical mitomycin-C. Potential applications of these findings include prophylactic use of topical mitomycin-C on glottic insults that commonly progress from granulation tissue formation to scarring and decreased vocal fold function.     

Neoplasia intraepitelial conjuntival. Interferón como terapia de rescate tras fracaso de la mitomicina C

Clinical caseThe case of a 60 year-old male with a conjunctival lesion diagnosed as conjunctival intraepithelial neoplasia (CIN), who was treated with mitomycin-C for 3 weeks with minimal improvement. The therapy was change to interferon 2B. Six month later, and after a complete remission of the lesion, the treatment was suspended, with no signs of relapse.DiscussionThe treatment of these lesions is currently made with chemotherapy and immunotherapy agents, such as mitomycin-C, 5-fluorouracil, and interferon alfa 2B. The latter, even although is the least used, gives excellent results with fewer secondary effects than mitomycin-C, resulting in an optimal therapy for the non-invasive treatment of CIN lesions.     

Scleral free auto-implant plug with mitomycin as limitation of trepanosclerectomy flow in glaucoma filtering surgery

The purpose of this study is to evaluate the effect of trephination with free scleral auto-implant plug exposed to Mitomycin-C out of the eye, in surgical treatment of primary open-angle glaucoma (POAG), in comparison with efficacy of trabeculectomy with MMC (32 eyes with POAG of patients, younger than 55 years — group 1). Trephination with scleral auto-implant plug with MMC was done on 35 eyes of patients, younger than 55 years, with POAG (group 2). The postoperative follow-up was 28.52 ± 8.78 months. Surgical procedure: A limbal 1.0 mm diameter trephination is made beneath the limbus-based conjunctival flap, a small iridectomy is performed. From the external layers of the trephine button one third of the corneoscleral thickness, in the form of a thin disc, is excised. The scleral disc, a free auto-implant, is dipped into liquid containing MMC with concentration 0.2 mg/ml for 5 minutes, outside the eye. Afterwards the scleral disc soaked with MMC is carefully irrigated with 150 ml of BSS and placed in the external part of the trephine fistula in primary position and stabilized with two interrupted 10-0 nylon sutures. The operation is ended as a typical trabeculectomy. The final success rate in terms of IOP (IOP < 14 mmHg) was 100%, without or with antiglaucoma medication, in both groups, but the number of postoperative complications was significantly lower in group 2. Trephination with free scleral auto-implant plug soaked with MMC may represent a viable alternative to trabeculectomy with MMC; the scleral plug may be taken out of the eye and exposed to antimetabolite outside the eye to minimize toxicity.     

翼状胬肉术中应用丝裂霉素与羊膜移植的效果比较

目的 观察翼状胬肉术中应用丝裂霉素与新鲜羊膜移植的效果.方法 将66例(72眼)原发性翼状胬肉随机分为两组,丝裂霉素C组33例(36眼),羊膜移植组33例(36眼).结果 丝裂霉素C组术后复发2眼(复发率为5.56％);羊膜移植组术后复发1眼(复发率为2.50％).结论 翼状胬肉术中应用丝裂霉素C与移植羊膜均能有效降低胬肉术后的复发率.两组比较差异无统计学意义(P＞0.05).     

定量丝裂霉素在小梁切除术中的应用观察

目的:观察定量丝裂霉素应用于小梁切除术中抗增殖的疗效及并发症发生率。方法:慢性闭角型青光眼术48例(66只眼)分两组,用药组小梁切除加丝裂霉素6.6ug应用;对照组单纯小梁切除。比较两组术后滤过泡存在时间及并发症发生率。用UBM检查滤过泡形态及浅前房原因,OCT检查黄斑水肿。结果:用药组33只眼,术后3个月时3只眼滤过泡囊样变。UBM检查1年时31只眼滤过泡形态良好,2只眼包裹瓣下有潜腔。术后Ⅱ°浅前房1只眼。UBM示睫状体浅脱离。对照组术后1年滤过泡粘连8只眼(P=0.039)。2只眼囊变。25只眼滤泡形态良好。术后浅前房Ⅱ°4只眼,UBM示2只眼睫状体脱离。术后1年眼压用药组15.88mmHg±2.64mmHg,对照组15.52mmHg±2.45mmHg。OCT检查无黄斑水肿发生。结论:小梁切除术中小剂量应用丝裂霉素滤过泡形成率高,安全无严重并发症发生。     

In vitro Antigenotoxicity of Ulva rigida C. Agardh （Chlorophyceae） Extract against Induction of Chromosome Aberration,Sister Chromatid Exchange and Micronuclei by Mutagenic Agent MMC

Objective To determine the in vitro possible clastogenic and cytotoxic activities of Ulva rigida crude extracts （URE）, and identify their antigenotoxic and protective effects on chemotherapeutic agent mitomycine-C （MMC）. Methods Anti-clastogenic and anti-genotoxic activities of Ulva rigida crude extracts （URE） were studied using chromosome aberration （CA）, sister chromatid exchange （SCE）, and micronuclei （MN） tests in human lymphocytes cultured in vitro. Results The chromosome aberration, sister chromatid exchange or micronuclei tests showed that URE at concentrations of 10, 20, and 40 lag/mL had no clastogenic activity in human lymphocyte cell culture. Three doses of URE significantly decreased the number of chromosomal aberrations and the frequencies of SCE and MN when compared with the culture treated with MMC （P〈0.0001）. Conclusion Although URE itself is not a clastogenic or cytotoxic substance, it possesses strong antigenotoxic, anti-clastogenic, and protective effects on MMC in vitro.     

Mitomycin C and conjunctival autograft for recurrent pterygium

Purpose To observe the efficiency of intraoperative low-dose Mitomycin-C combined with conjunctival autograft in the treatment of recurrent pterygium. Methods Fifteen eyes with recurrent pterygium were included in this study. The mean age of the patients was 51.6 ± 11.4 (9 men, 6 women). All patients underwent excision of the pterygium tissue and subconjunctival fibrous tissue with a no cautery approach. 0.2 mg/ml Mitomycin-C (0.02%) was applied for 3 min. Conjunctival autograft was obtained from the superotemporal bulbar conjunctiva of the same eye. Eyes were followed for a mean period of 21.0 ± 9.1 months. Results Recurrence was seen in two eyes (13.3%) during the follow-up period. The only complication seen was graft edema (two eyes; 13.3%) which healed after pressure patching. Graft necrosis, scleral melting or failure of revascularization was not noted. Conclusion Intraoperative application of 0.2 mg/ml Mitomycin-C combined with conjunctival autograft reduces recurrence in recurrent pterygium cases, with minimal complications.     

Phase II study of mitomycin-C, adriamycin, cisplatin (MAP) and Bleomycin-CCNU in patients with advanced cancer of the anal canal: An eastern cooperative oncology group study E7282

Summary Metastatic anal cancer is a rare disease in the Western hemisphere and current treatment modalities are not effective. In this study, patients with advanced epithelial cancer of the anal canal received MAP followed by Bleomycin and CCNU upon progression of disease. Twelve out of twenty eligible patients had a partial response 60%, (95% CI {36% −81%}). No complete responses were observed. The median survival was 15 months (95% CI {6–20} months). The median time to progression or death was 8 months (95% CI {4–9 months}). Toxicities were moderate and tolerable with routine supportive care; there were 2 cases of grade 3 vomiting, 2 cases of respiratory distress (one grade 1 and one grade 3), one case each of grade 3 leg cramps and cardiac arrhythmia. Of particular note were 7 cases of grade 3 hematologic toxicity. Two patients had grade 4 leukopenia and thrombocytopenia, respectively, that resolved without sequelae. The combination therapy of MAP followed by Bleomycin and CCNU for patients with advanced anal cancer, not amenable to radiotherapy or surgery, results in a moderate objective response but with moderate toxicities. This regimen and sequence is worthy of further study especially in combination with colony stimulating factors, however, its tolerability may be most applicable for patients who have had minimal prior therapy. This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, MD, Chair) and supported in part by Public Health Service grants CA14958, CA23318, CA13650, CA25988, CA15488, CA 66636, CA21115 from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.