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Experimental Eye Research Apr 2022Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven... (Review)
Review
Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven treatment is lowering intraocular pressure (IOP), the most important risk factor. Glaucoma filtration surgery (GFS) can effectively lower IOP. However, approximately 10% of all surgeries fail yearly due to excessive wound healing, leading to fibrosis. GFS animal models are commonly used for the development of novel treatment modalities. The aim of the present review was to provide an overview of available animal models and anti-fibrotic drug candidates. MEDLINE and Embase were systematically searched. Manuscripts until September 1st 2021 were included. Studies that used animal models of GFS were included in this review. Additionally, the snowball method was used to identify other publications which had not been identified through the systematic search. Two hundred articles were included in this manuscript. Small rodents (e.g. mice and rats) are often used to study the fibrotic response after GFS and to test drug candidates. Due to their larger eyes, rabbits are better suited to develop medical devices. Novel drugs aim to inhibit specific pathways, e.g. through the use of modulators, monoclonal antibodies, aqueous suppressants or gene therapy. Although most newly studied drugs offer a higher safety profile compared to antimetabolites, their efficacy is in most cases lower when compared to MMC. Current literature on animal models and potential drug candidates for GFS were summarized in this review. Future research should focus on refining current animal models (for example through the induction of glaucoma prior to undertaking GFS) and standardizing animal research to ensure a higher reproducibility and reliability across different research groups. Lastly, novel therapies need to be further optimized, e.g. by conducting more research on the dosage, administration route, application frequency, the option of creating combination therapies, or the development of drug delivery systems for sustained release of anti-fibrotic medication.
Topics: Animals; Fibrosis; Filtering Surgery; Glaucoma; Intraocular Pressure; Mice; Mitomycin; Models, Animal; Pharmaceutical Preparations; Rabbits; Rats; Reproducibility of Results
PubMed: 35114212
DOI: 10.1016/j.exer.2022.108972 -
Annals of Medicine and Surgery (2012) May 2022Direct Vision Internal Urethrotomy (DVIU) is regarded as the most popular and frequently used minimal invasive approach for treating urethral stricture. However, the... (Review)
Review
OBJECTIVES
Direct Vision Internal Urethrotomy (DVIU) is regarded as the most popular and frequently used minimal invasive approach for treating urethral stricture. However, the application of this procedure is limited due to the high recurrence rate. Recent trials have the benefit of mitomycin C as adjuvant therapy to reduce the stricture recurrence in DVIU procedures. In this meta-analysis, we aim to determine the efficacy of mitomycin C as adjuvant therapy for DVIU.
METHODS
A systematic literature search was carried out from Embase, ScienceDirect, and PubMed published up to September 2021. Relevant Randomized Controlled Trials (RCTs) were screened using our eligibility criteria. The quality assessment of the RCT was assessed using Cochrane RoB 2. The outcome was measured as an Odds Ratio (OR) with 95% Confidence Intervals (CIs). Statistical analyses were performed using RevMan 5.4.
RESULTS
We included four RCTs in the meta-analysis, with a total of 392 patients with urethral strictures undergoing DVIU. The pooled analysis showed a significantly lower recurrence rate in patients undergoing DVIU with additional treatment of mitomycin C compared to the control group (OR 0.27, 95% CI 0.16-0.45, p < 0.0001).
CONCLUSION
Our findings highlight the benefit of adjuvant treatment with mitomycin C to reduce the incidence of urethral stricture recurrence after DVIU procedures.
PubMed: 35638056
DOI: 10.1016/j.amsu.2022.103576 -
International Archives of... Jan 2020Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. To evaluate the effectiveness and safety of... (Review)
Review
Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time ≥ one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61-76%; I = 17.3%). A total of 52% of the patients (95%CI: 39-64%, 11 studies; I = 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36-61%, 11 studies; I = 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3-18%, 9 studies; I = 79.8%). The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis.
PubMed: 31915466
DOI: 10.1055/s-0039-1700582 -
World Journal of Urology Dec 2022Urothelial carcinoma has a higher incidence in renal transplanted patients according to several registries (relative risk × 3), and the global prognosis is inferior... (Review)
Review
PURPOSE
Urothelial carcinoma has a higher incidence in renal transplanted patients according to several registries (relative risk × 3), and the global prognosis is inferior to the general population. The potential impact of immunosuppressive therapy on the feasibility, efficacy, and complications of endovesical treatment, especially Bacillus Calmette-Guerin, has a low level of evidence. We performed a systematic review that aimed to assess the morbidity and oncological outcomes of adjuvant endovesical treatment in solid organ transplanted patients.
METHODS
Medline was searched up to December 2021 for all relevant publications reporting oncologic outcomes of endovesical treatment in solid organ transplanted patients with NMIBC. Data were synthesized in light of methodological and clinical heterogeneity.
RESULTS
Twenty-three retrospective studies enrolling 238 patients were included: 206 (96%) kidney transplants, 5 (2%) liver transplants, and 2 (1%) heart transplants. Concerning staging: 25% were pTa, 62% were pT1, and 22% were CIS. 140/238 (59%) patients did not receive adjuvant treatment, 50/238 (21%) received mitomycin C, 4/238 (2%) received epirubicin, and 46/238 (19%) received BCG. Disease-free survival reached 35% with TURBT only vs. 47% with endovesical treatment (Chi-square test p = 0.08 OR 1.2 [0.98-1.53]). The complication rate of endovesical treatment was 12% and was all minor (Clavien-Dindo I).
CONCLUSION
In solid organ transplanted patients under immunosuppressive treatment, both endovesical chemotherapy and BCG are safe, but the level of evidence concerning efficacy in comparison with the general population is low. According to these results, adjuvant treatment should be proposed for NMIC in transplanted patients as in the general population.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Retrospective Studies; BCG Vaccine; Administration, Intravesical; Adjuvants, Immunologic; Organ Transplantation; Neoplasm Invasiveness; Neoplasm Recurrence, Local
PubMed: 36367586
DOI: 10.1007/s00345-022-04188-9 -
The Cochrane Database of Systematic... Aug 2021Trabeculectomy is a surgical treatment for glaucoma to lower intraocular pressure with high success rates; however, it is often associated with an increased rate of... (Review)
Review
BACKGROUND
Trabeculectomy is a surgical treatment for glaucoma to lower intraocular pressure with high success rates; however, it is often associated with an increased rate of cataract formation. Cataract can cause symptoms such as glare in bright conditions, foggy vision, and difficulty in driving at night. Cataract extraction surgery is highly successful in improving vision, but it comes at a cost of trabeculectomy failure, with a reported risk of 30% to 40%. An additional intervention to promote trabeculectomy survival after cataract extraction is needed. This review encompassed all adjunctive therapies used at the time of cataract surgery to increase trabeculectomy survival rate.
OBJECTIVES
To investigate the effect of the adjunctive modulation of wound healing during cataract surgery on the survival of a previously functioning trabeculectomy.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 April 2021.
SELECTION CRITERIA
We planned to include all randomised controlled trials (RCTs) of participants who had a functioning trabeculectomy and were undergoing cataract surgery that compared any adjunctive therapy intended to modulate wound healing (such as 5-fluorouracil, mitomycin C, or anti-vascular endothelial growth factor (VEGF) therapy) with no adjuvant therapy. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Our primary outcome was trabeculectomy failure at 6 months and 12 months after cataract surgery. Secondary outcomes were mean intraocular pressure difference from pre-cataract surgery baseline to 6 to 18 months post-cataract surgery; number of medications required to control eye pressure compared to before cataract surgery; bleb appearance as measured by a summation score of the Moorfields bleb grading system or other equivalent numerical grading systems; visual field progression measured by difference in mean deviation from baseline; and any complications.
MAIN RESULTS
We did not identify any RCTs of adjunctive modulation of wound healing during cataract surgery to promote survival of a previous trabeculectomy.
AUTHORS' CONCLUSIONS
There is a need for an RCT to investigate the role of adjuvant wound modulating therapy at the time of cataract surgery to promote survival of a functioning trabeculectomy.
Topics: Cataract; Cataract Extraction; Glaucoma; Humans; Trabeculectomy; Wound Healing
PubMed: 34355804
DOI: 10.1002/14651858.CD013664.pub2 -
Urologic Oncology Apr 2023Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies. (Review)
Review
BACKGROUND
Non-muscle invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence and progression, despite surgery and adjuvant therapies.
OBJECTIVE
To analyze the published results on the effectiveness of mitomycin C (MMC) applied with an electromotive drug administration device (EMDA) in the treatment of patients with non-muscle invasive bladder tumors.
METHOD
A systematic review was conducted using the PubMed and Google Scholar search platforms. We selected the studies that included the recurrence and/or progression rates or complete response rate in patients diagnosed with NMIBC according to their treatment and included MMC applied with EMDA. The last search was performed in November 2021.
RESULTS
The search yielded 64 articles; 11 articles met the selection criteria. In two of the 11 selected articles, mitomycin C was applied with an EMDA device (MMC-EMDA) as an ablative treatment, avoiding surgery in 50% of the patients. In 1 of the 11 studies, the application of MMC-EMDA was used as an induction treatment using a single preoperative instillation with promising results. In the remaining 8 studies, adjuvant MMC was applied with the EMDA device; in 3 of these 8 cases, treatment with MMC-EMDA alone was applied initially. In another3 cases the same treatment was applied after nonresponse to bacillus Calmette Guerin (BCG), and in the last 2 studies, MMC-EMDA was applied in combination with the classic therapy (BCG). All the studies selected supported the efficacy and safety of MMC-EMDA in patients with intermediate and high- risk bladder cancer. In 3 studies, adjuvant therapy with MMC-EMDA was performed in nonresponders to BCG, finding that adjuvant therapy with MMC-EMDA applied to BCG nonresponders without CIS avoided or delayed surgery.
CONCLUSIONS
The application of EMDA-enhanced MMC has been studied at different times of disease and with different administration protocols. It appears to delay bladder tumor recurrence and progression in certain populations. However, the methodological limitations of the published studies prevent definitive conclusions about its efficacy.
Topics: Humans; Mitomycin; Antibiotics, Antineoplastic; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms; Administration, Intravesical; Neoplasm Invasiveness
PubMed: 36328923
DOI: 10.1016/j.urolonc.2022.09.016 -
Scientific Reports Aug 2022Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical... (Meta-Analysis)
Meta-Analysis
Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.
Topics: Administration, Topical; Carcinoma, Squamous Cell; Conjunctival Neoplasms; Eye Neoplasms; Fluorouracil; Humans; Interferon alpha-2; Mitomycin; Retrospective Studies; Treatment Outcome
PubMed: 35987957
DOI: 10.1038/s41598-022-18545-6 -
Frontiers in Medicine 2022Pterygium is a common ocular surface disease. Recurrence is the greatest concern in the treatment of pterygium. Thus, a standardized and effective treatment modality...
BACKGROUND
Pterygium is a common ocular surface disease. Recurrence is the greatest concern in the treatment of pterygium. Thus, a standardized and effective treatment modality with minimal risk for complications is needed for the management of pterygium. The aim of this systematic review and meta-analysis was to evaluate different tissue grafting options, including conjunctival autograft (CAG) with mitomycin C (MMC), CAG alone, and amniotic membrane transplantation (AMT), for the management of primary pterygium.
METHODS
We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases for relevant studies. We included randomized controlled trials (RCTs) in which CAG + MMC and AMT were compared with surgical excision with CAG alone for the treatment of primary pterygium. The rates of recurrence and adverse events reported in the studies were also evaluated. Risk ratio (RR) was used to represent dichotomous outcomes. The data were pooled using the inverse variance weighting method. The quality of the evidence derived from the analysis was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials.
RESULTS
Twelve RCTs ( = 1144) were deemed eligible and included for analysis. Five RCTs had a low risk of bias, five had some concerns, and two had a high risk of bias. Subgroup analysis showed a statistically significant reduction in the rate of pterygium recurrence after CAG + MMC (RR = 0.12; 95% confidence interval [CI], 0.02-0.63). This outcome was rated as high-quality evidence according to the GRADE criteria. There were insignificant differences between the rates of recurrence after AMT and CAG (RR = 1.51; 95% CI, 0.63-3.65). However, this result was rated as low-quality evidence. Regarding adverse events, patients treated using AMT showed significantly lower rates of adverse events than those treated using CAG (RR = 0.46; 95% CI, 0.22-0.95). However, this finding was rated as low-quality evidence as well. CAG + MMC showed a safety profile comparable to that of surgical excision with CAG alone (RR = 1.81; 95% CI, 0.40-8.31). This result was also rated as low-quality evidence.
CONCLUSION
A single intraoperative topical application of 0.02% MMC during excision of pterygium followed by CAG has significantly shown to decrease the rate of pterygium recurrence to 1.4% with no severe complications.
PubMed: 36438046
DOI: 10.3389/fmed.2022.981663 -
Frontiers in Oncology 2023With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant...
Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guérin instillation in non-muscle-invasive bladder cancer: a network meta-analysis.
INTRODUCTION
With the shortage of bacillus Calmette-Guérin (BCG) vaccine, it is important to find an alternative to BCG instillation, which is the most commonly used adjuvant treatment for non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumor treatment (TURBt) to delay tumor recurrence. Hyperthermia intravesical chemotherapy (HIVEC) with mitomycin C (MMC) is a potential treatment choice. We aim to compare HIVEC with BCG instillation for the preventive efficacy of bladder tumor recurrence and progression.
METHODS
A network meta-analysis (NMA) was taken with MMC instillation and TURBt as the attached comparators. Randomized controlled trials (RCTs) with NIMBC patients after TURBt were included. Articles with pure BCG unresponsive patients and combined therapies were excluded. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023390363).
RESULTS
It was found that HIVEC had a non-significant 22% relative reduction in bladder tumor recurrence compared with BCG instillation [HIVEC vs. BCG: HR 0.78, 95% credible interval (CrI) 0.55-1.08] and a nonsignificant higher risk of bladder tumor progression (BCG vs. HIVEC: HR 0.77, 95% CrI 0.22-3.03).
DISCUSSION
HIVEC is a potential alternative to BCG, and it is expected to be the standard therapy for NMIBC patients after TURBt during the global shortage of BCG.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO identifier, CRD42023390363.
PubMed: 37251942
DOI: 10.3389/fonc.2023.1164932 -
Ophthalmology and Therapy Jun 2020To evaluate the effect of mitomycin-C (MMC) on the success of external (Ex-DCR) or endoscopic dacryocystorhinostomy (En-DCR).
PURPOSE
To evaluate the effect of mitomycin-C (MMC) on the success of external (Ex-DCR) or endoscopic dacryocystorhinostomy (En-DCR).
METHOD
A systematic review of randomized clinical trials of Ex- or En-DCR with and without the use of MMC to treat primary acquired nasolacrimal duct obstruction (NLDO) was done. Two authors independently searched six databases from 1990 to 2019, using the terms "dacryocystorhinostomy" and "mitomycin-C." Statistical and meta-analyses were performed using RevMan 5.3 software.
RESULTS
Twenty-seven studies involving 2158 surgeries were included in this systematic review. The Ex-DCR group comprised 14 studies [odds ratio (OR): 2.74; 95% confidence intervals (CI) 1.54-4.87; I = 30%], while the En-DCR group 13 studies (OR: 1.69; 95% CI 1.21-2.37; I = 0%). The use of MMC slightly increased the success rate of Ex- or En-DCR (OR: 2.1; 95% CI 1.52-2.9; I = 14%).
CONCLUSION
The intraoperative use of MMC is safe and slightly improves the success rate of Ex- or En-DCR. However, the evidence was very weak.
PubMed: 32342404
DOI: 10.1007/s40123-020-00253-x