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Abstract Purpose Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. Methods Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. Results Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p 0.05). No serious adverse effects were reported. Conclusions Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN .

To date, there is only one study investigating the physicochemical stability of diluted mitomycin (MMC) solutions prepared by using urea-containing Mitomycin medac as starting material. The aim of the study was to test the solubility of the new MMC formulation with regard to highly concentrated solutions and determine the physicochemical stability of clinically relevant MMC concentrations stored under different conditions in various primary containers.

AIM: To evaluate the safety and efficacy of posterior scleral application (a modified technique) of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma. METHODS: This retrospective study included 101 patients (115 eyes) with glaucoma (aged 12–83y) who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method. A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus. The mitomycin C concentration and exposure time were 0.2–0.5 mg/mL and 1–5min, respectively. Intraocular pressure, best-corrected visual acuity, and hypotensive medications were recorded at baseline and at the final visit. Complications, interventions required, and bleb morphology were recorded postoperatively. The primary outcome was trabeculectomy safety, including complications and bleb morphology; the secondary outcome was the trabeculectomy success rate. RESULTS: At the final follow-up [median 28mo, range 7–67mo and interquartile range (IQR) 13mo], the qualified (cumulative) success rate was 93.0% and the complete success rate was 60.0%. No bleb-related complications were observed. The mean height, extent, and vascularity grades were 0.6±0.9, 1.1±0.4, and 2.4±0.9, respectively. All Seidel tests were negative. The mean posteriority grade was 0.8±0.4. CONCLUSION: Trabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.

AbstractTrabeculectomy with adjunctive use of Mitomycin C (MMC) has been a benchmark for glaucoma filtration surgery for decades. However, there are many variations in the ways that the sponges soaked with MMC are applied during the trabeculectomy surgery. We herein describe our way of placing the MMC-soaked sponges to improve the safety and efficacy of the trabeculectomy. The sponges are placed vertically and posteriorly with the long side of the sponge perpendicular to the limbus, not parallel. This will reduce the size of the conjunctival wound at the limbus to preserve more virgin conjunctiva that can be used for repeated trabeculectomy when needed. This will also facilitate a more posteriorly directed flow of aqueous drainage that, in turn, may increase the success rate of the trabeculectomy. We have obtained encouraging results in our practice, and further large-scale randomized studies seem warranted.

To demonstrate a technique for minimally invasive endoscopic management of posterior urethral strictures, including those at the bladder neck and vesicourethral anastomosis. Herein, we have included endoscopic video footage from 3 patients with posterior urethral strictures, including 1 at the bladder neck, 1 at the vesicourethral anastomosis, and 1 in the bulbomembranous urethra. In each patient, we perform a direct visualization internal urethrotomy (DVIU) with incisions at the 5 and 7 o'clock positions to widen the urethral lumen, followed by injection of 2 mg mitomycin C (MMC) in a total volume of 5 mL sterile water. Herein, we describe our technique for the endoscopic management of posterior urethral strictures, including those in the prostatic urethra and bladder neck. MMC injection, in conjunction with traditional DVIU, adds minimally to the complexity and length of the procedure but may substantially improve long-term surgical outcomes. Bladder outlet obstruction due to stenosis or stricture of the posterior urethra is a common urologic diagnosis whose etiology can often be traced to prior urethral manipulation or iatrogenic trauma. While Americal Urological Assicuation (AUA) guidelines state that dilation or direct visualization internal urethrotomy (DVIU) should be offered for bulbar strictures measuring less than 2 cm in length, recent evidence suggests that DVIU with or without MMC injection may have utility in the management of bladder neck or vesicourethral anastomotic contractures. We have found that DVIU with subsequent MMC injection is a viable minimally invasive approach for the treatment of posterior urethral strictures. While more data are needed to better understand the long-term success rates of these procedures, this approach should be considered for patients with a bladder outlet obstruction secondary to a short stricture of the posterior urethra, bladder neck, or vesicourethral anastomosis. [ABSTRACT FROM AUTHOR]

Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success.

Isolated from Streptomyces caespitosus, mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It has been employed in pterygium surgery, ocular surface neoplasia, and refractive surgery. Currently, there is no definite consensus on the treatment protocols for each of the aforementioned applications. Although its benefits in the management of corneal and external diseases are promising, MMC use has potential complications including endothelial cell loss, corneal perforation, scleral melt, secondary glaucoma, iritis, and endophthalmitis. This article will review the literature regarding the use of MMC in the field of cornea and external disease and describe protocols employed with corresponding outcomes.

Abstract Objectives The objectives of the study are to explore tolerability, acceptability and oncological outcomes for patients with high‐risk non‐muscle‐invasive bladder cancer (NMIBC) treated with hyperthermic intravesical chemotherapy (HIVEC) and mitomycin‐C (MMC) at our institution. Patients and Methods Our single‐institution, observational study consists of consecutive high‐risk NMIBC patients treated with HIVEC and MMC. Our HIVEC protocol included six weekly instillations (induction), followed by two further cycles of three instillations (maintenance) (6 + 3 + 3) if there was cystoscopic response. Patient demographics, instillation dates and adverse events (AEs) were collected prospectively in our dedicated HIVEC clinic. Retrospective case‐note review was performed to evaluate oncological outcomes. Primary outcomes were tolerability and acceptability of HIVEC protocol; secondary outcomes were 12‐month recurrence‐free, progression‐free and overall survival. Results In total, 57 patients (median age 80.3 years) received HIVEC and MMC, with a median follow‐up of 18 months. Of these, 40 (70.2%) had recurrent tumours, and 29 (50.9%) had received prior Bacillus Calmette–Guérin (BCG). HIVEC induction was completed by 47 (82.5%) patients, but only 19 (33.3%) completed the full protocol. Disease recurrence (28.9%) and AEs (28.9%) were the most common reasons for incompletion of protocol; five (13.2%) patients stopped treatment due to logistical challenges. AEs occurred in 20 (35.1%) patients; the most frequently documented were rash (10.5%), urinary tract infection (8.8%) and bladder spasm (8.8%). Progression during treatment occurred in 11 (19.3%) patients, 4 (7.0%) of whom had muscle invasion and 5 (8.8%) subsequently required radical treatment. Patients who had received prior BCG were significantly more likely to progress (p = 0.04). 12‐month recurrence‐free, progression‐free and overall survival rates were 67.5%, 82.2%, and 94.7%, respectively. Conclusions Our single‐institution experience suggests that HIVEC and MMC are tolerable and acceptable. Oncological outcomes in this predominantly elderly, pretreated cohort are promising; however, disease progression was higher in patients pretreated with BCG. Further randomised noninferiority trials comparing HIVEC versus BCG in high‐risk NMIBC are required.

Abstract Introduction Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. Methods This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon’s capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon’s capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. Results Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon’s capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. Conclusion Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon’s capsule seems to be the safer application site of MMC during trabeculectomy.

Polychromatophilic erythrocytes (PCE) are a suitable target to assess both acute and chronic genotoxic stress in in vivo models. Mitomycin C (MMC), an alkylating mutagenic agent forming cross-links between DNA strands, is widely employed to induce genotoxic stress in experiment and, specifically, to evaluate chromosomal genotoxicity in mouse erythrocytes using the in vivo micronucleus test. While most of the available studies focus on acute genotoxic stress caused by high doses of mutagens, there are very few works aimed at studying chronic mutagenic exposures. The aim of the present study was to determine MMC concentration that would induce chromosomal genotoxic, but not cytotoxic, effect in apolipoprotein E gene knockout mice (ApoE–/–) during chronic exposure to this agent. The design of the study included four groups of ApoE–/– mice injected with two different MMC doses, 0.1 and 0.5 mg/kg, once and thrice a week, as well as two control group. Each group consisted of four females and one male. To assess genotoxicity, 1000 PCE isolated from the femoral bone marrow were counted in each sample, the cells with micronuclei were identified, and the percentage of reticulocytes was counted. A dose of 0.5 mg/kg showed a clear cytotoxic effect, as manifested in impaired erythropoiesis (reduced percentage of reticulocytes). A dose of 0.1 mg/kg induced a pronounced genotoxic effect without reaching the threshold of cytotoxicity. These results can be instrumental in selecting MMC doses for the experiments that require the modeling of chronic genotoxic stress in laboratory animals. [ABSTRACT FROM AUTHOR]

Background Extramammary Paget disease (EMPD) is a cutaneous neoplasm that can metastasize to the lymph nodes and distant organs, resulting in a poor prognosis. For unresectable distant metastases of EMPD, no consensus has been reached regarding optimal chemotherapy owing to a lack of data. Objectives To evaluate the efficacy of three regimens: docetaxel (DTX) monotherapy; combination therapy with 5-fluorouracil, epirubicin, carboplatin, vincristine and mitomycin C (FECOM); and tegafur (S-1) monotherapy. Methods This single-centre retrospective study included 32 patients diagnosed with unresectable EMPD and treated with chemotherapy between 2002 and 2022 at the National Cancer Center Hospital in Japan. Patient characteristics, responses to treatment and survival data were evaluated for each of the first-line therapies. Results Among the 17 patients who received DTX monotherapy, the response rate (RR) and disease control rate (DCR) were 47% and 77%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 12.3 months [95% confidence interval (CI) 6.1–26.6] and 19.2 months (95% CI 8.5–not reached), respectively. Among the 11 patients who received combination FECOM chemotherapy, the RR and DCR were 55% and 64%, respectively. The median PFS and OS were 6.8 months (95% CI 3.5–not reached) and 13.4 months (95% CI 8.6–21.3), respectively. Among the four patients who received S-1 monotherapy, the RR and DCR were 0% and 25%, respectively. The median PFS and OS were 5.4 months (95% CI 2.3–not reached) and 12.5 (95% CI 2.3–not reached) months, respectively. Conclusions Further investigations with prospective analysis are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Zonula occludens‐1 (ZO‐1) is a scaffolding protein of tight junctions, which seal adjacent epithelial cells, that is also expressed in adherens junctions. The distribution pattern of ZO‐1 differs among stratified squamous epithelia, including that between skin and oral buccal mucosa. However, the causes for this difference, and the mechanisms underlying ZO‐1 spatial regulation, have yet to be elucidated. In this study, we showed that epithelial turnover and proliferation are associated with ZO‐1 distribution in squamous epithelia. We tried to verify the regulation of ZO‐1 by comparing normal skin and psoriasis, known as inflammatory skin disease with rapid turnover. We as well compared buccal mucosa and oral lichen planus, known as an inflammatory oral disease with a longer turnover interval. The imiquimod (IMQ) mouse model, often used as a psoriasis model, can promote cell proliferation. On the contrary, we peritoneally injected mice mitomycin C, which reduces cell proliferation. We examined whether IMQ and mitomycin C cause changes in the distribution and appearance of ZO‐1. Human samples and mouse pharmacological models revealed that slower epithelial turnover/proliferation led to the confinement of ZO‐1 to the uppermost part of squamous epithelia. In contrast, ZO‐1 was widely distributed under conditions of faster cell turnover/proliferation. Cell culture experiments and mathematical modelling corroborated these ZO‐1 distribution patterns. These findings demonstrate that ZO‐1 distribution is affected by epithelial cell dynamics. [ABSTRACT FROM AUTHOR]

Since EXTRA, a non-randomized phase II trial with 31 patients, explored the use of capecitabine, mitomycin and radiation therapy (RT) in the treatment of localized squamous cell carcinoma of the anal canal (SCCAC), this treatment has been considered as an acceptable alternative to infusional 5-FU. However, the differences in efficacy between capecitabine and 5-FU in chemoradiation therapy (CRT) with simultaneous integrated boost (SIB) radiation therapy (SIB-IMRT) for local SCCAC are not well documented. Patients included in this prospective monocentric cohort study were treated with SIB-RapidArc (a unique RT method treatment for all patients: identical technique, volume and constraints for at-risk organs), mitomycin C and 5-FU each day of RT for 7 weeks (group 1) or capecitabine each day of RT (group 2). Patients treated between July 2009 and August 2017 (group 1) and between November 2012 and April 2018 (group 2) for local SCCAC T2-4 classified as N, M0 or T, N1-3, M0 were included. Primary endpoints were progression-free survival (PFS) and acute toxicities. Results: One hundred forty-seven patients were included, 91 in group 1 and 56 in group 2. The two groups were statistically comparable in terms of sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and TNM. With a median duration of follow-up of 53.5 months, the PFS rate at 3 years was 80% for group 1 and 75% for group 2 (p = 0.32). The 3-year colostomy-free survival rate was 92% for group 1 and 85% for group 2 (p = 0.11). The rate of patients with at least one grade 3 or higher acute toxicity was 35.5% in group 1 and 21.4% in group 2 (p = 0.10), with a trend of fewer acute toxicities with capecitabine. Conclusion: Capecitabine/mitomycin in combination with SIB RapidArc radiation therapy for anal cancer seems as effective as 5-FU-based chemotherapy and is well tolerated with minimal toxicity. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy followed by surgery for locoregionally advanced penile carcinoma (LAPSCC) is associated with severe toxicity and a 1-year survival probability of ∼50%. We aimed to evaluate the safety and efficacy of chemoradiotherapy (CRT) as the primary treatment for LAPSCC and the association of high-risk human papillomavirus (hrHPV) with the outcome. This was a prospective, single-center, single-arm study of CRT in LAPSCC, defined as a large/inoperable primary tumor, large palpable nodes, suspicion of extranodal extension or pelvic nodal involvement, and no distant metastases. CRT consisted of 49.5 Gy (33 × 1.5 Gy) on affected inguinal and pelvic areas combined with intravenous mitomycin C on day 1 and capecitabine on radiation days. Primary tumors and positron emission tomography/computed tomography–positive deposits received a boost of 59.4 Gy (33 × 1.8 Gy). The response was evaluated by 18F-fluorodeoxyglucose positron emission tomography/computed tomography. If feasible, patients with residual/recurrent disease underwent salvage surgery. The primary endpoint was 1-year progression-free survival (PFS), reached when 1-year PFS was ≥50%. Other endpoints were 2-year PFS, overall survival, and toxicity rates. Kaplan-Meier survival curves were compared using the log-rank test. Thirty-three patients were included: 29 (88%) with stage IV disease (T4 any-N M0 and/or any-T N3 M0) and 8 (24%) with hrHPV-positive disease. Median follow-up was 41 months. Thirty-two completed CRT. Eleven (33%) experienced ≥1 grade 3 treatment-related adverse event. There were no grade 4 or 5 treatment-related events. Twenty-four patients (73%) responded, including 13 (39%) complete responses. Nine patients (27%) underwent salvage surgery, and an additional 8 patients underwent later surgery (together 52%). One- and 2-year PFS were 34% and 31%, respectively. One- and 2-year overall survival were 73% and 46%, respectively. No significant difference between patients with hrHPV-positive and -negative tumors was observed. CRT is a viable treatment option for LAPSCC with acceptable toxicity. CRT can result in an enduring response. If patients have residual tumor, salvage surgery is feasible. HrHPV status was not associated with outcomes. [ABSTRACT FROM AUTHOR]

Background: Congenital Choanal Artesia (CCA) is a rare cause of upper airway obstruction, yet it is the most common congenital anomaly of the nose. While the unilateral condition could be undiagnosed, bilateral CCA may be life-threatening, especially for newborns. Some CCA may be associated with other congenital abnormalities, which leads to a systematic screening during the diagnostic assessment. The diagnosis is easy. However, surgical management is still controversial. Methods: We conducted a retrospective study gathering data on management of CCA over 42 months. We reported epidemiological aspects and results of our series, and discussed management issues. Results: We operated 22 choanae using the endoscopic technique. The age of bilateral CCA patients on the day of surgery ranged from 8 to 21 days (mean 11.7+/_ 2.6 days). Their birth weight ranged from 2.9 to 4.5 kg (mean 3.4 +/_ 0.5 kg), and their gestational age ranged from 30 to 41 weeks. Surgery duration for neonatal bilateral CCA repair ranged from 75 to 110 min (mean 90 min +/_ 11.5 min). We performed an exclusive endonasal endoscopic approach for all patients with no stenting or mitomycin C application. We deplore one post operative complication related to minor palatal perforation resolved spontaneously. Conclusion: Since newborns solely depend on nasal breathing during the first month of life, bilateral CCA is an emergency. Endonasal endoscopic management is the primary procedure. Currently, surgery steps are standardized. However, how to prevent post-operative synechiae and restenosis is still controversial. The mainstream is meticulous post-operative nursing with frequent endonasal saline irrigation, regular removal of crust, and prevention of inflammation due to reflux or infection. [ABSTRACT FROM AUTHOR]

A multicomponent reaction eliminates operational challenges and boosts the atom economy of the reaction process. A vast class of compounds known as pyrrolidine‐derived heterocycles act as crucial scaffolding for anticancer drugs. The scientists are inspired to create several pyrrolizine derivatives and test their potential antitumor activity against a wide range of cancer types by Mitomycin C's unique anticancer capabilities. We developed an efficient and highly discriminating three‐component reaction between isatin/indenoquinoxaline, l‐phenyl alanine, and quinolinyl‐derived chalcones in methanol results in the synthesis of biologically active novel spiro pyrrolidines that contain three pharmacophoric cores, heterocyclic quinoline scaffold, pyrrolidines, and oxindoles in a single‐molecular framework viz 1,3‐dipolar cycloaddition reaction. FT‐IR, NMR, and mass spectroscopic methods were used to elucidate the structures of the synthesized compounds. With butyrated hydroxy toluene serving as a positive control, the synthesized compounds were tested for antioxidant properties utilizing nitric oxide, 1,1‐diphenylpicrylhydrazide, and super oxide radicals, and the results were analyzed. [ABSTRACT FROM AUTHOR]

Objective: To compare the success rate of external dacryocystorhinostomy with intramucosal injection and sponge application of Mitomycin C to circumosteal mucosa. Study Design: Quasi-experimental study Place and Duration of Study: Eye Department, Combined Military Hospital, Jhelum Cantt Pakistan, from Feb 2019 to Dec 2021. Methodology: One hundred ten patients were selected and randomly allocated into two equal Groups labelled Group-A and Group-B. Group-A patients received 0.1ml of intramucosal injection of 0.02% Mitomycin C, and Group-B patients had 0.02% Mitomycin C applied with a sponge to the circumboreal mucosa. The result of DCR was evaluated at six months and declared successful if the patients were asymptomatic of epiphora and a patent lacrimal passage was found on probing and irrigation. Failure was defined as symptomatic epiphora along with regurgitation on probing and syringing. In failed cases, nasal endoscopy was performed along with probing. Results: Success rates of external dacryocystorhinostomy in the Intramucosal Injection Group was 96%, and in the Sponge Application Group, it was 92%. A comparison of both techniques depicted a statistically insignificant difference in success rate (p=0.60). Conclusion: Mitomycin C use as an adjunctive agent during external dacryocystorhinostomy is a safe and effective technique in achieving a high rate of success, and the route of application, whether applied topically or injected intramucosal does not significantly affect the outcome of this procedure. [ABSTRACT FROM AUTHOR]

The treatment of implant‐associated bacterial infections and biofilms is an urgent medical need and a grand challenge because biofilms protect bacteria from the immune system and harbor antibiotic‐tolerant persister cells. This need is addressed herein through an engineering of antibody‐drug conjugates (ADCs) that contain an anti‐neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non‐specific counterpart, in suspension and within biofilms, in vitro, and in an implant‐associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms. [ABSTRACT FROM AUTHOR]

Background: Bacillus Calmette–Guerin (BCG) maintenance therapy is the standard adjuvant treatment of high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). However, the problems of shortages and the adverse effects, both local and systemic, that it causes lead to the search for alternatives with devices that improve the penetration of intravesical chemotherapeutics. Materials and methods: Prospective observational study was conducted from August 2018 to August 2022. Patients diagnosed with intermediate and high-risk NMIBC without CIS who received one of the following three treatments were included: BCG in induction protocol with six weekly instillations and maintenance with three weekly instillations at months 3, 6, and 12. MMC was applied by Physionizer® 30 device with a current of 20 mA for 30 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (EMDA group). MMC was applied by COMBAT BRS System V2.0 device at 43 ± 0.5 ℃ for 60 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (HIVEC group). The primary objective was to compare the 24-month recurrence-free rate between the three groups. The secondary objectives were to evaluate the rate free of progression at 24 months and the degree of toxicity of the treatments. Results: One hundred and eighty-three patients divided into a HIVEC group with sixty-one patients, EMDA group with fifty-nine patients, and BCG group with sixty-three patients. After a mean follow-up of 25 months (IQR 13–36), the 24-month recurrence-free rate was 82.1% for HIVEC, 80% for EMDA, and 84.6% for BCG (p > 0.05), and a progression-free rate at 24 months of 95.6% for HIVEC, 98.3% for EMDA, and 92.9% for BCG (p > 0.05). No statistically significant differences were found between the three groups with respect to the degree of reported adverse events. Conclusion: Adjuvant treatment with BCG or MMC applied with COMBAT or EMDA does not present differences in the recurrence-free rate and progression at 24 months in our population of patients with intermediate- and high-risk NMBC without CIS. [ABSTRACT FROM AUTHOR]

In this study, the biological properties of novel borenium and borinium compounds in terms of their oxidative, genotoxic, and cytotoxic effects were assessed on cultured human peripheral blood cells, as well as several types of cancer cells. Our results revealed that the borinium compounds yielded the best results in terms of supporting total antioxidant capacity (TAC). In fact, borenium 1, borenium 2, borenium 3, borinium 4, and borinium 5 compounds elevated TAC levels of cultured human blood cells at rates of 42.8%, 101.5%, 69.8%, 33.3%, and 49.2%, respectively. There were no statistically significant differences (p > 0.05) between the negative control and the groups treated with all borinium and borenium concentrations from the micronucleus (MN) and chromosome aberration (CA) assays, demonstrating the non-genotoxic effects. Moreover, borenium 1 (60.7% and 50.7%), borenium 2 (70.4% and 57.2%), borenium 3 (53.1% and 45.2%), borinium 4 (55.1% and 48.1%), and borinium 5 (51.0% and 36.1%) minimized the mitomycin C(MMC)-induced genotoxic damages at different rates as determined using CA and MN assays, respectively. Again, it was found that the borinium compounds exhibited higher cytotoxic activity on cancer cells when compared to borenium compounds. Consequently, in light of our in vitro findings, it was suggested that the novel borinium and borenium compounds could be used safely in pharmacology, cosmetics, and various medical fields due to their antioxidant and non-genotoxic features, as well as their cytotoxicity potential on cancer cells. [ABSTRACT FROM AUTHOR]

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell–targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of trabeculectomy (Trab MMC) on visual field (VF) progression in eyes with glaucoma and high myopia.Patients and Methods: Patients diagnosed with primary open-angle glaucoma or exfoliation glaucoma who underwent Trab MMC as the first glaucoma surgery along with ≥ 3 VF tests preoperatively and postoperatively were enrolled. High myopia was defined as an axial length ≥ 26.5 mm. Postoperative reductions in intraocular pressure (IOP) were assessed by survival analysis using IOP measurements obtained preoperatively. The longitudinal trends of the outcome measures were evaluated using linear mixed models.Results: Thirty-five eyes of 32 patients were included in this study, including 22 eyes of 20 patients in non-highly myopic group and 13 eyes of 12 patients in highly myopic group. IOP decreased after Trab MMC, and the survival rate did not differ significantly in relation to axial length. Linear mixed-model analyses suggested that the inhibitory effects of Trab MMC on the rate of mean deviation (MD) changes were significant in the non-highly myopic group (− 0.53 ± 0.15 dB/year preoperatively to − 0.16 ± 0.13 dB/year postoperatively; P = 0.004), but not in the highly myopic group (− 0.66 ± 0.19 dB/year preoperatively to − 0.48 ± 0.18 dB/year postoperatively; P = 0.32).Conclusion: Trab MMC reduced IOP in both highly myopic and non-highly myopic eyes, and IOP reduction was very similar in both groups. The VF deterioration rate decreased in both groups, but the change was weaker and nonsignificant in the highly myopic group. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of Ex-PRESS implantation (EXP) with that of trabeculectomy (TLE) with mitomycin C for maintaining low target intraocular pressure (IOP) in patients with open-angle glaucoma.Patients and Methods: Patients were randomly assigned to receive EXP or TLE. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤ 18 mmHg [criterion A], 5 mmHg ≤ IOP ≤ 15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤ 12 mmHg [criterion C]) representing reductions of at least 20% below the baseline on two consecutive follow-up visits 3 months post-surgery, with or without antiglaucoma medication and without further glaucoma surgery. Participants were divided into three subgroups based on baseline mean deviation (MD) values: early (MD ≥ − 6 dB), moderate (− 6 dB > MD ≥ − 12 dB), and advanced (− 12 dB > MD). Survival rates were calculated by subgroup.Results: A total of 73 patients, including 30 in the EXP group and 43 in the TLE group, were included in the study. No significant differences in baseline ocular or demographic characteristics were found between the two groups. No significant difference in IOP was noted every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the EXP and TLE groups, respectively. Moreover, there was no difference in success rate based on glaucoma level. Many glaucoma medications administered before surgery were associated with a higher failure rate in the TLE group but not in the EXP group.Conclusion: Both procedures resulted in similar IOP reductions and success rates for a low target IOP. The number of preoperative glaucoma medications was a risk factor for TLE failure. [ABSTRACT FROM AUTHOR]

We evaluated the use of BCG and Mitomicin C instillations administered with Electromotive Drug Administration (EMDA) in patients with nonmuscle invasive bladder cancer in whom Bacillus Calmette-Guerin (BCG) therapy had failed, in order to provide bladder preservation for these patients. We evaluated the oncological outcomes and tolerability in a long follow up This treatment seems to be safe and to provide good responses in well selected patients, without a high progression rate. Background: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed.Objectives: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. Material and Methods: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. Results: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. Conclusion: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases. [ABSTRACT FROM AUTHOR]

Purpose: Mitomycin C (MMC) is normally used to avoid scar formation in trabeculectomy. There has been a shift from conventional delivery via soaked sponges to preoperative injection of MMC. This study aimed to compare the effectiveness of a modified two-stage low-dose intra-Tenon injection with soaked sponges of MMC for trabeculectomy over a 1-year follow-up period. Methods: This retrospective study enrolled patients with glaucoma undergoing modified trabeculectomy with a two-stage intra-Tenon injection (0.01%, 0.1 mL) or soaked sponges (0.02%) of MMC. In the former group, patients received intra-Tenon injection of MMC (the first stage) at least 4 h before trabeculectomy (the second stage). Patient characteristics, preoperative and postoperative intraocular pressure, antiglaucoma medication use, complications, and post-trabeculectomy surgical interventions were recorded during a 1-year follow-up period. Results: There were 36 and 35 eyes in the injection and sponge groups, respectively, in 58 patients. The injection group showed significantly lower intraocular pressure (p < 0.05) at every time point except on postoperative day 1 and week 1, fewer medications at the 1-year follow-up (p = 0.018), and a higher complete success rate (p = 0.011) than the sponge group. Both techniques showed a significant reduction in intraocular pressure and medication use at the 1-year follow-up. There were no significant differences in complications between both groups. Conclusion: Our two-stage intra-Tenon MMC injection technique resulted in lower postoperative intraocular pressure, less antiglaucoma medication use, and fewer needling revisions compared to the sponge technique. [ABSTRACT FROM AUTHOR]

Purpose: Ocular surface squamous neoplasia (OSSN) comprises a wide spectrum of squamous tumors, from which corneal/conjunctival intraepithelial neoplasia (CIN) is the most common one. The classic treatment is complete excision, but recurrence rates are high. Antineoplastic drugs such as mitomycin C (MMC) and interferon alpha 2b (IFNα2b) have been used as adjuvants or as primary treatment. To evaluate the efficacy and safety of topical IFNα2b and MMC in patients with CIN, a phase IIb double-blind clinical trial was performed. Methods: Patients diagnosed with localized CIN were evaluated by slit lamp and impression cytology and were randomly given MMC 0.04% or INF2b (1 million IU/mL) 4 times daily until neoplasia resolution. Time of resolution and frequency of adverse effects were analyzed to determine the pharmacological efficacy and safety of both medications. Results: Seventeen patients were included. Nine patients were treated with MMC and 8 with IFNα2b. All patients responded to treatment. The resolution time in days was 59.11 ± 24.02 in patients treated with MMC and 143.50 ± 47.181 in those treated with IFNα2b (p < 0.001). In the MMC group, one recurrence was reported (11%). There were no recurrences at 2 years of follow-up in the IFNα2b group. Regarding adverse effects, one or more mild adverse reaction occurred in 77% of patients managed with MMC and in 50% of patients managed with IFNα2b (p > 0.05). No serious adverse effects were reported. Conclusions: Topical chemotherapy with MMC and IFNα2b demonstrate pharmacological safety and efficacy. Therefore, these drugs could be considered as primary therapies for localized CIN. [ABSTRACT FROM AUTHOR]

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10–15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5–68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17–92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC. [ABSTRACT FROM AUTHOR]

Purpose: Since there is a lack of clear information regarding the benefit to combine supportive therapies (such as artificial tears) to mitomycin C (MMC) in the treatment of ocular surface neoplasia, the primary purpose of the study was to evaluate hyaluronic acid eye drops and hyaluronic acid-conjugated lactobionic acid (LACTOyal FREE) eye drops as supportive therapy. Methods: Retrospective evaluation of patients with ocular surface squamous neoplasia or conjunctival melanocytic tumor treated with MMC, who had used also artificial tears as supportive treatment. A 6-month follow-up with evaluation of subjective and objective tests for ocular surface integrity was conducted. Results: A total of 35 patients were analyzed, most of them with squamous disease (71.4%). The break-up time (BUT), Ocular Surface Disease Index (OSDI) and Schirmer test values showed a significant difference at any time point with overall population. No statistical difference was found among subgroups (Lactoyal vs No Lactoyal). Conclusion: The use of an ancillary therapy based on hyaluronic acid allows to improve both subjective and objective ocular parameters, reducing MMC induced adverse effects. Meantime, hyaluronic acid-conjugated lactobionic acid eye drops highlighted the same advantages with a more positive trend in OSDI results. [ABSTRACT FROM AUTHOR]

Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the C57BL/6 mouse recurrent erosion model. Here, high resolution imaging of mouse corneas was performed at D1, D7, and D28 after dulled-blade debridement injury in C57BL/6 mice. Around 50% of these mice have frank corneal erosions at D28 after wounding. A detailed assessment of corneas revealed the involvement of M2 macrophages in both frank and developing erosions at early stages of their formation. [ABSTRACT FROM AUTHOR]

Anamnesis: A descriptive series of six cases of dogs with glaucoma are presented comparing the fibrosis inhibition effect of three drugs used during trabeculectomy (TEC). Clinical findings: The patients were diagnosed with primary chronic closedangle glaucoma refractory to topical medical treatment with no pupillary light reflex and negative eyeblink response to threat and ocular pain. Therapeutic approach: Two patients received an intraoperative application of bevacizumab; two received 5-fluorouracil; and two, mitomycin C. Intraocular pressure (IOP) and filtering ampoule were observed on days 1, 7, 30, 60, and 90 post-surgery. Results and conclusion: Bevacizumab regulated IOP under 25 mmHg, constituting the drug of choice for dogs with primary closed-angle glaucoma without previous positive response to topical therapy and subjected to TEC, when compared with 5-fluorouracil and MMC regarding the inhibitory effect of fibrosis. [ABSTRACT FROM AUTHOR]

To measure the changes in treatment patterns for non-muscle invasive bladder cancer before and during the Bacillus Calmette-Guerin (BCG) drug shortage. We used a 5% random sample of Medicare beneficiaries and identified 7971 bladder cancer patients (2648 pre-BCG shortage and 5323 during the shortage) ≥66 years of age who received intravesical treatment within 1 year of diagnosis between 2010 and 2017. The BCG shortage period was defined from July 2012 ongoing. Full induction treatment with BCG, mitomycin C, gemcitabine, or other intravesical agents was defined as receiving ≥5 of 6 treatments within 60 days. State-level BCG use before and during the drug shortage was compared in US states reporting at least 50 patients in each period. Independent variables included year of index date, age, sex, race, rurality, and region of residence. BCG utilization rates decreased 5.9% in the shortage period (95% CI (−8.2%)-(−3.7%)). The proportion of patients that completed a full induction course of BCG decreased from 31.0% in the pre-shortage period to 27.6% in the shortage period (P =.002). 84% of reporting states (16 of 19) had decreased BCG utilization ranging between 5% and 36% compared to pre-shortage rates. During the BCG drug shortage, eligible bladder cancer patients were less likely to receive gold standard intravesical BCG with a large variation in treatment patterns between US states. [ABSTRACT FROM AUTHOR]

Purpose: Ethanol and mitomycin C (MMC) are clinically used to treat corneal diseases such as LASEK and LASIK surgery. In this study, we investigated the effects of time-dependent alcohol and MMC in cultured rat limbal stem cells (LSCs) to determine the appropriate time for the use of this compound in the clinical setting. Methods: LSCs (N = 10 eyes) isolated from male Wistar rats were cultured and characterized; then, isolates were divided into three groups. One group was exposed to a 20% concentration of ethanol for 5, 10, 15, 20, 25, and 30 s, and cell viability was assessed one, three, and five days following ethanol exposure using an MTT assay. To investigate the effect of MMC, cells in the second group were treated with 0.02% MMC in various periods (i.e., 15 s, 30 s, 60 s, 90 s, and 120 s) and time-dependent responses of cultured LSCs were recorded. Cells in the third group were co-treated with ethanol and MMC; then, dose and time dependency was evaluated. Results: In comparison with the viable cells in the control group, ethanol markedly decreased the viability of cells in a time-dependent manner in days one and three. On day five, the viability of LSCs was improved significantly (p < 0.05) in comparison with day one. The number of viable progenitor cells was significantly decreased after MMC treatment in a time-dependent manner, as determined by the MTT assay (p < 0.001). The use of mitomycin, along with alcohol, decreased cell viability in all groups treated with ethanol + MMC compared to the control on days one, three, and five (p < 0.0001). Conclusions: Our findings suggest that ethanol and MMC reduced cell viability in cultured LSCs in a time-dependent manner. In addition, when LSCs were exposed to alcohol alone, they had a better recovery process within 5 days in comparison to when exposed to mitomycin alone or mitomycin + alcohol. [ABSTRACT FROM AUTHOR]

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Abstract Background Although traditional surgical procedures for glaucoma (such as trabeculectomy and tube-shunt implantation) can significantly reduce intraocular pressure (IOP), they are associated with numerous complications, some of which are vision-threatening, or involve prolonged recovery or a highly intensive postoperative course. Micro-invasive glaucoma surgery (MIGS) procedures have shown better safety but reduced efficacy in achieving target IOP. Combinations of these methods have led to the development of subconjunctival micro-invasive procedures with safety comparable to traditional surgery and greater efficacy than minimally invasive methods. This review describes the use of one of these devices, the poly(styrene-block-isobutylene-block-styrene) (SIBS)-based PreserFlo MicroShunt (Santen, Emeryville, CA), in the surgical treatment of patients with glaucoma. Main text The MicroShunt is an 8.5-mm tube made of an inert polymer with no endplate, an internal diameter of 70 μm, and fins intended to prevent peritubular flow and anchor the device within the sclera to prevent proximal migration into the eye. Following ab externo implantation, the tube provides a conduit for flow of aqueous humor from the anterior chamber into the subconjunctival/sub-Tenon space. Clinical trials to date have shown that, when paired with mitomycin C (MMC) treatment, MicroShunt implantation significantly reduced both IOP and the number of glaucoma medications. These IOP-lowering results were found both when surgery was performed alone and with phacoemulsification. The MicroShunt also showed a safety profile comparable to that of traditional filtering surgery. Conclusions The MicroShunt and other novel subconjunctival procedures have shown substantial IOP reductions while mitigating hypotony-related complications. MMC, which modulates fibrosis and scarring postoperatively, is essential to surgical success. Randomized, long-term clinical trials will further clarify the role of controlled micro-incisional device-assisted ab externo glaucoma filtering surgery in long-term glaucoma management.

Aim To compare between the outcomes of cauterized conjunctival autograft (CA) with and without mitomycin C (MMC) in primary pterygium surgery. Patients and methods This prospective interventional comparative study included 50 eyes in 50 patients with primary pterygium. Patients were randomly assigned into two equal groups: group 1 underwent pterygium excision with cauterized CA fixation, and group 2 underwent pterygium excision with cauterized CA fixation and intraoperative application of 0.02% MMC for 3 min. All patients underwent a preoperative, first day, first week, first month, third month, and sixth month postoperative ophthalmic examination. Any intraoperative or postoperative complications were recorded. Primary outcomes were reported as incidence of recurrence and any major (sight threatening) complications. Secondary outcomes were reported as any minor complications. Results A total of 50 patients (28 males and 22 females, with male to female ratio 1 : 1.3) were included in this study. Complications encountered in our study included recurrence of pterygium, which occurred in one (4%) eye in group 1 and 0 eyes in group 2. Two (8%) eyes in group 1 versus one (4%) eye in group 2 showed subconjunctival hemorrhage, one (4%) eye in group 2 showed focal scleral thinning, and one (4%) eye in group 2 showed a corneal epithelial defect. There was no statistically significant difference between the two groups regarding the incidence of any complication (P>0.05). Conclusion Cauterized CA without MMC is a safe and effective procedure for the surgical treatment of primary pterygium. There was no added benefit to intraoperative MMC application.

Background Punctal stenosis is a progressive constriction of the puncta with resultant epiphora. One of the most effective treatment options is one- to four-snip punctoplasty with or without mitomycin C (MMC). Aim The aim of this study was to assess the effectiveness of intraoperative MMC in increasing the success rate of three-snip punctoplasty in cases of punctal stenosis. Patients and methods This is a nonrandomized interventional prospective comparative study that was conducted at the Department of Ophthalmology, Al-Hussein and Bab El Sheria Al-Azhar University Hospitals, Cairo, Egypt. It included 31 eyes of 18 patients who underwent three-snip punctoplasty. The patients were divided into two groups: group 1 (15 eyes), in which MMC was not used during surgery, and group 2 (16 eyes), in which MMC was used intraoperatively for 2 min. Complete ocular examinations were performed in all patients using the slit lamp. Punctal stenosis grading was done as follows: grade 0 (absent punctum), grade 1 (a membrane covering the papilla), grade 2 (less than average size, however, can be recognized), grade 3 (normal), grade 4 (small slit

PURPOSE: To develop a new dry eye syndrome (DES) animal model by injecting mitomycin C (MMC) into the lacrimal glands (LGs) of rabbits evaluated by clinical examinations. MATERIALS AND METHODS: A volume of 0.1 mL of MMC solution was injected in the LG and the infraorbital lobe of the accessory LG of rabbits for DES induction. Twenty male rabbits were separated into three groups, the control group, and different concentration of MMC, (MMC 0.25: 0.25 mg/mL or MMC 0.50: 0.5 mg/mL) were tested. Both MMC-treated groups received MMC twice injection on day 0 and day 7. Assessment of DES included changes in tear production (Schirmer's test), fluorescein staining pattern, conjunctival impression cytology, and corneal histological examination. RESULTS: After MMC injection, no obvious changes in the rabbit's eyes were noted by slit-lamp examination. Both the MMC 0.25 and the MMC 0.5 groups revealed decreased tear secretion after injection, and the MMC 0.25 group showed a continuous decrease in tear secretion up to 14 days. Fluorescent staining showed punctate keratopathy in both MMC-treated groups. In addition, both MMC-treated groups demonstrated decreased numbers of conjunctival goblet cells after injection. CONCLUSION: This model induced decreased tear production, punctate keratopathy, and decreased numbers of goblet cells, which are consistent with the current understanding of DES. Therefore, injecting MMC (0.25 mg/mL) into the LGs is an easy and reliable method to establish a rabbit DES model which can apply in new drug screening.

Background: The aim was to evaluate the long-term outcome and efficacy of primary trabeculectomy with adjunctive mitomycin c (MMC) for treating glaucoma. Methods: We examined the medical records of 286 eyes that underwent trabeculectomy between 2008 and 2009 at the University Eye Hospital in Freiburg, Germany. Preoperative and follow-up data were collected, including intraocular pressure (IOP) measurements, surgical glaucoma interventions, and prescribed glaucoma medication. The first success criterion was defined as IOP ≤ 15 mmHg with no use of pressure-lowering medication by the patient, the second criterion was defined as the absence of surgical revision, and the third criterion as no further IOP-lowering surgery excluding early revisions following trabeculectomy. Statistical analyses comprised Cox regression and Kaplan–Meier survival estimations. Results: The mean follow-up duration was 1841 days (5 years). The mean preoperative IOP was 26.1 mmHg. Evaluating the success criteria at the time of average follow-up yielded a success rate of only 25% for the first criterion but 80% for both the second and third success criteria. Conclusions: The findings suggest that trabeculectomy with adjunctive MMC can be an effective procedure for permanently lowering IOP. However, surgical revisions and/or further glaucoma surgeries might still be needed. The long-term success rate is lower in comparison to previous research, which may be explained by the stricter success criteria in our study.

Objective: Toxic anterior segment (TASS) is a rare acute sterile anterior segment inflammation that typically develops within 12 to 24 hours after an anterior segment surgery. The purpose of this case report is to alert surgeons to the possibility of this complication following any anterior segment surgery, including trabeculectomy, and to highlight the possible etiologies and measures to prevent it.Patient and method: A 58-year-old male glaucoma patient was initially managed medically for primary open angle glaucoma with antiglaucoma medications. There was rapidly progressive glaucomatous optic nerve damage in his left eye within the following year, despite the use of antiglaucoma medications, hence the need for trabeculectomy.Result: The post-operative condition of the patient’s eye was stormy with diffuse limbus-to-limbus corneal edema and profound Descemet’s membrane folds, among other features of TASS, with associated deteriorating visual acuity. Conclusion: Although there is no documented report of TASS following trabeculectomy with mitomycin C, surgeons should be alerted to this possibility. Preventive measures include extreme care to avoid errors while preparing and administering diluted solutions, especially medications that are administered into the intracameral space.

The morphological response of HepG2 cells to mitomycin C was analyzed using a multichannel quartz crystal microbalance system equipped with a home-built movable microscope that enables the simultaneous acquisition of cell images and measurements of eight-channel quartz crystal microbalance. After 24 h of cell seeding, mitomycin C was injected into the culture medium. During the attachment process, the resonant frequency decreased, and the curves fitted well with the first-order lag response. Analysis of the response to mitomycin C revealed that the resonant frequency response curves varied with mitomycin C concentration. When the mitomycin C concentration was 20 μmol L−1, the response to the change in resonant frequency was rapid, and the response curves fitted well with the first-order lag response. The first-order lag response indicates that the response occurred simultaneously for all cells. The results showed that the time constant was independent of the tested mitomycin C concentration between 20 and 100 μmol L−1. These results suggested that different cell death processes occurred by mitomycin C. The findings of this study suggest that the system can be used to investigate cell death in adherent cells.

The main purpose of this study is to evaluate and understand the clinical profile of patients presenting to an Indian tertiary care referral centre with Laryngotracheal Stenosis (LTS) and also to emphasise on the outcomes after treatment in these patients. This is a prospective observational study conducted at a tertiary care referral centre which included 18 patients diagnosed with LTS. All patients were evaluated clinically and radiologically to evaluate the degree of stenosis, site and length of the stenotic segment involved, intervened surgical procedure, intraoperative and postoperative complications following the procedure were all documented and taken into consideration. The data collected was analysed. The most common etiological cause of LTS was post intubation (77.8%). 61.5% among the 13 intubated patients had a history of intubation for more than 10 days. 83.3% of the cases had stenosis at the level of the subglottis and cervical trachea level. Post intubational airway stenosis is the most common cause of LTS. A precise assessment of the laryngotracheal complex is the cornerstone of LTS management. The choice of treatment depends on the location, severity, and length of stenosis, as well as on the patient's comorbidities, history of previous interventions, and on the expertise of the surgical team. Application of topical Mitomycin c during surgery reduces the incidence of granulations. Close postoperative follow up for a long time and the necessity of more than one intervention improves results and can spare patients the morbidity and mortality associated with acute airway obstruction. [ABSTRACT FROM AUTHOR]

A viral shunt can occur when phages going through a lytic cycle, including lysogenic phages triggered by inducing agents (e.g. mitomycin C), results in host lysis and the release of cell constituents and virions. The impact of a viral shunt on the carbon, including methane cycle in soil systems is poorly understood. Here, we determined the effects of mitomycin C on the aerobic methanotrophs in a landfill cover soil. To an extent, our results support a mitomycin C-induced viral shunt, as indicated by the significantly higher viral-like particle (VLP) counts relative to bacteria, elevated nutrient concentrations (ammonium, succinate), and initially impaired microbial activities (methane uptake and microbial respiration) after mitomycin C addition. The trend in microbial activities at <2 days largely corresponded to the expression of the pmoA and 16S rRNA genes. Thereafter (>11 days), the active bacterial community composition significantly diverged in the mitomycin C-supplemented incubations, suggesting the differential impact of mitomycin C on the bacterial community. Collectively, we provide insight on the effects of mitomycin C, and potentially a viral shunt, on the bacteria in the soil environment. [ABSTRACT FROM AUTHOR]

Isolated from Streptomyces caespitosus, mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It has been employed in pterygium surgery, ocular surface neoplasia, and refractive surgery. Currently, there is no definite consensus on the treatment protocols for each of the aforementioned applications. Although its benefits in the management of corneal and external diseases are promising, MMC use has potential complications including endothelial cell loss, corneal perforation, scleral melt, secondary glaucoma, iritis, and endophthalmitis. This article will review the literature regarding the use of MMC in the field of cornea and external disease and describe protocols employed with corresponding outcomes. [ABSTRACT FROM AUTHOR]

Results from HIVEC-II show no oncological benefit from chemohyperthermia over the control treatment. Adverse events following chemohyperthermia were low of grade and short-lived, although these patients were less likely to complete their treatment. Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non–muscle-invasive bladder cancer (NMIBC). To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC. HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital. Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min. The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat. A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51–69%) in the CHT arm and 60% (95% CI 50–68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62–1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09–10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83–9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77–8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control). CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment. The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non–muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment. [ABSTRACT FROM AUTHOR]

Introduction: Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. Methods: This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon's capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon's capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. Results: Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon's capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. Conclusion: Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon's capsule seems to be the safer application site of MMC during trabeculectomy. [ABSTRACT FROM AUTHOR]