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Eye (London, England) Jun 2020Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could... (Review)
Review
Pterygia are common conjunctival degenerations with well-documented risk factors but an unclear pathogenesis. Better understanding of the pathogenesis of pterygium could lead to improved surgical outcomes and decreased postoperative recurrence. Currently, pterygium excision with conjunctival autograft remains the preferred surgical technique to decrease pterygium recurrence. Many adjuvant therapies have been used in pterygium surgery to varying degrees of success. Topical cyclosporine, an immunosuppressive medication, in conjunction with conjunctival autograft was found to be most successful in decreasing pterygium recurrence according to a recent meta-analysis. Other adjuvant therapies such as mitomycin-C (MMC), 5-fluorouracil (5-FU), and beta-irradiation have also been used, though usage of these may cause multiple adverse effects. Recent research indicates that interactions between mouse double minute 2 (MDM2) and p53 could play a role in the occurrence of pterygium. Nutlin, an MDM2 antagonist, was found to have significantly less toxicity in conjunctival cells when compared with MMC on laboratory analysis of pterygium samples.
Topics: Animals; Conjunctiva; Follow-Up Studies; Mice; Mitomycin; Ophthalmologic Surgical Procedures; Pterygium; Recurrence; Transplantation, Autologous
PubMed: 32029918
DOI: 10.1038/s41433-020-0786-3 -
European Urology Sep 2022BC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer (MIBC), demonstrated improvement in locoregional control by adding... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
BC2001, the largest randomised trial of bladder-sparing treatment for muscle-invasive bladder cancer (MIBC), demonstrated improvement in locoregional control by adding fluorouracil and mitomycin C to radiotherapy (James ND, Hussain SA, Hall E, et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012;366:1477-88). There are limited data on long-term recurrence risk.
OBJECTIVE
To determine whether benefit of adding chemotherapy to radiotherapy for MIBC is maintained in the long term.
DESIGN, SETTING, AND PARTICIPANTS
A phase 3 randomised controlled 2 × 2 factorial trial was conducted. Between 2001 and 2008, 458 patients with T2-T4a N0M0 MIBC were enrolled; 360 were randomised to radiotherapy (178) or chemoradiotherapy (182), and 218 were randomised to standard whole-bladder radiotherapy (108) or reduced high-dose-volume radiotherapy (111). The median follow-up time was 9.9 yr. The trial is registered (ISRCTN68324339).
INTERVENTION
Radiotherapy: 55 Gy in 20 fractions over 4 wk or 64 Gy in 32 fractions over 6.5 wk; concurrent chemotherapy: 5-fluorouracil and mitomycin C.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Locoregional control (primary endpoint), invasive locoregional control, toxicity, rate of salvage cystectomy, disease-free survival (DFS), metastasis-free survival (MFS), bladder cancer-specific survival (BCSS), and overall survival. Cox regression was used. The analysis of efficacy outcomes was by intention to treat.
RESULTS AND LIMITATIONS
Chemoradiotherapy improved locoregional control (hazard ratio [HR] 0.61 [95% confidence interval {CI} 0.43-0.86], p = 0.004) and invasive locoregional control (HR 0.55 [95% CI 0.36-0.84], p = 0.006). This benefit translated, albeit nonsignificantly, for disease-related outcomes: DFS (HR 0.78 [95% CI 0.60-1.02], p = 0.069), MFS (HR 0.78, [95% CI 0.58-1.05], p = 0.089), overall survival (HR = 0.88 [95% CI 0.69-1.13], p = 0.3), and BCSS (HR 0.79 [95% CI 0.59-1.06], p = 0.11). The 5-yr cystectomy rate was 14% (95% CI 9-21%) with chemoradiotherapy versus 22% (95% CI 16-31%) with radiotherapy alone (HR 0.54, [95% CI 0.31-0.95], p = 0.034). No differences were seen between standard and reduced high-dose-volume radiotherapy.
CONCLUSIONS
Long-term findings confirm the benefit of adding concomitant 5-fluorouracil and mitomycin C to radiotherapy for MIBC.
PATIENT SUMMARY
We looked at long-term outcomes of a phase 3 clinical trial testing radiotherapy with or without chemotherapy for patients with invasive bladder cancer. We concluded that the benefit of adding chemotherapy to radiotherapy was maintained over 10 yr.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Fluorouracil; Follow-Up Studies; Humans; Mitomycin; Muscles; Urinary Bladder Neoplasms
PubMed: 35577644
DOI: 10.1016/j.eururo.2022.04.017 -
Ophthalmology Dec 2022To report 5-year treatment outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To report 5-year treatment outcomes in the Primary Tube Versus Trabeculectomy (PTVT) Study.
DESIGN
Multicenter randomized clinical trial.
PARTICIPANTS
A total of 242 eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 patients in the tube group and 117 patients in the trabeculectomy group.
METHODS
Patients were enrolled at 16 clinical centers and randomly assigned to treatment with a tube shunt (350-mm Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC) (0.4 mg/ml for 2 minutes).
MAIN OUTCOME MEASURES
The primary outcome measure was the rate of surgical failure, defined as intraocular pressure (IOP) > 21 mmHg or reduced < 20% from baseline, IOP ≤ 5 mmHg, reoperation for glaucoma, or loss of light perception. Secondary outcome measures included IOP, glaucoma medical therapy, and visual acuity.
RESULTS
The cumulative probability of failure after 5 years of follow-up was 42% in the tube group and 35% in the trabeculectomy group (P = 0.21; hazard ratio = 1.31; 95% confidence interval = 0.86-2.01). At 5 years, IOP (mean ± standard deviation) was 13.4 ± 3.5 mmHg in the tube group and 13.0 ± 5.2 mmHg in the trabeculectomy group (P = 0.52), and the number of glaucoma medications (mean ± standard deviation) was 2.2 ± 1.3 in the tube group and 1.3 ± 1.4 in the trabeculectomy group (P < 0.001).
CONCLUSIONS
Trabeculectomy with MMC and tube shunt surgery produced similar IOPs after 5 years of follow-up in the PTVT Study, but fewer glaucoma medications were required after trabeculectomy. No significant difference in the rate of surgical failure was observed between the 2 surgical procedures at 5 years.
Topics: Humans; Trabeculectomy; Follow-Up Studies; Glaucoma Drainage Implants; Glaucoma; Intraocular Pressure; Mitomycin; Treatment Outcome
PubMed: 35835337
DOI: 10.1016/j.ophtha.2022.07.003 -
Der Ophthalmologe : Zeitschrift Der... Mar 2021The main goals of glaucoma treatment are to preserve the visual function and maintain as high a quality of life as possible at a cost acceptable to society. Therefore,... (Review)
Review
BACKGROUND
The main goals of glaucoma treatment are to preserve the visual function and maintain as high a quality of life as possible at a cost acceptable to society. Therefore, it is crucial to carefully observe each individual patient in order to determine an individual and personalized treatment approach.
MATERIAL AND METHODS
This article summarizes the advantages and disadvantages of medicinal glaucoma treatment as well as traditional methods of glaucoma surgery, based on the current state of knowledge. The article explains the various mechanisms of action of new minimally invasive procedures, introduces the methods mostly commonly used in Germany and gives recommendations for preoperative care and postoperative follow-up.
RESULTS/CONCLUSION
In addition to the plethora of medicinal glaucoma treatments and classical surgical procedures, new minimally invasive treatment alternatives have become available in the past few years. The latter are an option for an earlier surgical intervention, especially in naïve or previously treated patients who appear to be unsuitable for medicinal treatment.
Topics: Germany; Glaucoma; Humans; Intraocular Pressure; Mitomycin; Quality of Life; Retrospective Studies; Trabeculectomy; Treatment Outcome
PubMed: 32632493
DOI: 10.1007/s00347-020-01146-x -
Eye (London, England) Apr 2023Ocular surface squamous neoplasia (OSSN) is the most common non-melanocytic tumour of the ocular surface. Surgical excision with wide margins using the "no-touch" method... (Review)
Review
Ocular surface squamous neoplasia (OSSN) is the most common non-melanocytic tumour of the ocular surface. Surgical excision with wide margins using the "no-touch" method was originally the most popular treatment for OSSN. However, in the past two decades, the use of topical medications for OSSN treatment has gained a reputation amongst ophthalmologists for being an effective alternative to surgical excision. Furthermore, technological advancements, such as those seen in high-resolution optical coherence tomography (HR-OCT) for the anterior segment, have facilitated the diagnosis and monitoring of OSSN. When selecting a topical agent, interferon alpha-2b (IFNα-2b) and 5-fluorouracil (5-FU) are two of the gentlest medications used for OSSN and are often considered first line therapies due to their high-resolution rates and mild side effect profiles. Mitomycin C (MMC), on the other hand, has a highly toxic profile; therefore, while effective, in our hands it is considered as a second-line treatment for OSSN if the other modalities fail. In addition, newer and less studied agents, such as immune checkpoint inhibitors, retinoic acid, aloe vera, and anti-vascular endothelial growth factor have anti-neoplastic properties and have shown potential for the treatment of OSSN. We enclose an updated literature review of medical treatments for OSSN.
Topics: Humans; Conjunctival Neoplasms; Fluorouracil; Mitomycin; Interferon alpha-2; Eye Neoplasms; Carcinoma, Squamous Cell; Retrospective Studies
PubMed: 36754986
DOI: 10.1038/s41433-023-02434-x -
Turkish Journal of Ophthalmology Jun 2023Isolated from , mitomycin C (MMC) has various applications in the management of corneal and external disease due to its ability to modulate cellular proliferation. It... (Review)
Review
Isolated from , 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.
Topics: Humans; Mitomycin; Photorefractive Keratectomy; Lasers, Excimer; Cornea
PubMed: 37345314
DOI: 10.4274/tjo.galenos.2023.97932 -
Ophthalmic Plastic and Reconstructive...This study aimed to report the performance of the large language model ChatGPT (OpenAI, San Francisco, CA, U.S.A.) in the context of lacrimal drainage disorders.
PURPOSE
This study aimed to report the performance of the large language model ChatGPT (OpenAI, San Francisco, CA, U.S.A.) in the context of lacrimal drainage disorders.
METHODS
A set of prompts was constructed through questions and statements spanning common and uncommon aspects of lacrimal drainage disorders. Care was taken to avoid constructing prompts that had significant or new knowledge beyond the year 2020. Each of the prompts was presented thrice to ChatGPT. The questions covered common disorders such as primary acquired nasolacrimal duct obstruction and congenital nasolacrimal duct obstruction and their cause and management. The prompts also tested ChatGPT on certain specifics, such as the history of dacryocystorhinostomy (DCR) surgery, lacrimal pump anatomy, and human canalicular surfactants. ChatGPT was also quizzed on controversial topics such as silicone intubation and the use of mitomycin C in DCR surgery. The responses of ChatGPT were carefully analyzed for evidence-based content, specificity of the response, presence of generic text, disclaimers, factual inaccuracies, and its abilities to admit mistakes and challenge incorrect premises. Three lacrimal surgeons graded the responses into three categories: correct, partially correct, and factually incorrect.
RESULTS
A total of 21 prompts were presented to the ChatGPT. The responses were detailed and were based according to the prompt structure. In response to most questions, ChatGPT provided a generic disclaimer that it could not give medical advice or professional opinion but then provided an answer to the question in detail. Specific prompts such as "how can I perform an external DCR?" were responded by a sequential listing of all the surgical steps. However, several factual inaccuracies were noted across many ChatGPT replies. Several responses on controversial topics such as silicone intubation and mitomycin C were generic and not precisely evidence-based. ChatGPT's response to specific questions such as canalicular surfactants and idiopathic canalicular inflammatory disease was poor. The presentation of variable prompts on a single topic led to responses with either repetition or recycling of the phrases. Citations were uniformly missing across all responses. Agreement among the three observers was high (95%) in grading the responses. The responses of ChatGPT were graded as correct for only 40% of the prompts, partially correct in 35%, and outright factually incorrect in 25%. Hence, some degree of factual inaccuracy was present in 60% of the responses, if we consider the partially correct responses. The exciting aspect was that ChatGPT was able to admit mistakes and correct them when presented with counterarguments. It was also capable of challenging incorrect prompts and premises.
CONCLUSION
The performance of ChatGPT in the context of lacrimal drainage disorders, at best, can be termed average. However, the potential of this AI chatbot to influence medicine is enormous. There is a need for it to be specifically trained and retrained for individual medical subspecialties.
Topics: Humans; Dacryocystorhinostomy; Lacrimal Duct Obstruction; Nasolacrimal Duct; Mitomycin; Intubation; Silicones
PubMed: 37166289
DOI: 10.1097/IOP.0000000000002418 -
Nature Aging May 2023The mysteries behind immune aging and its related inflammation are being unmasked. The research of Jin et al. reveals that the defective turnover of damaged mitochondria...
The mysteries behind immune aging and its related inflammation are being unmasked. The research of Jin et al. reveals that the defective turnover of damaged mitochondria in CD4 T cells from aged individuals results in the exacerbated secretion of mitochondrial DNA, fuelling inflammaging and impairing immune responses.
Topics: T-Lymphocytes; Mitomycin; Mitochondria
PubMed: 37198439
DOI: 10.1038/s43587-023-00412-2 -
Molecules (Basel, Switzerland) May 2021This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-]benzimidazoles, and... (Review)
Review
This review article provides a perspective on the synthesis of alicyclic and heterocyclic ring-fused benzimidazoles, imidazo[4,5-]benzimidazoles, and imidazo[5,4-]benzimidazoles. These heterocycles have a plethora of biological activities with the iminoquinone and quinone derivatives displaying potent bioreductive antitumor activity. Synthesis is categorized according to the cyclization reaction and mechanisms are detailed. Nitrobenzene reduction, cyclization of aryl amidines, lactams and isothiocyanates are described. Protocols include condensation, cross-dehydrogenative coupling with transition metal catalysis, annulation onto benzimidazole, often using CuI-catalysis, and radical cyclization with homolytic aromatic substitution. Many oxidative transformations are under metal-free conditions, including using thermal, photochemical, and electrochemical methods. Syntheses of diazole analogues of mitomycin C derivatives are described. Traditional oxidations of -(cycloamino)anilines using peroxides in acid via the -amino effect remain popular.
Topics: Benzimidazoles; Cyclization; Imidazoles; Mitomycin
PubMed: 34064312
DOI: 10.3390/molecules26092684 -
The Urologic Clinics of North America Feb 2020Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been... (Review)
Review
Non-muscle-invasive bladder cancer can be a challenging disease to manage. In recent years, hyperthermia therapy in conjunction with intravesical therapy has been gaining traction as a treatment option for bladder cancer, especially if Bacillus Calmette-Guerin might not be available. Trials of intravesical chemotherapy with heat are few and there has been considerable heterogeneity between studies. However, multiple new trials have accrued and high-quality data are forthcoming. In this review, we discuss the role of combined intravesical hyperthermia and chemotherapy as a novel approach for the treatment of bladder cancer.
Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Humans; Hyperthermia, Induced; Mitomycin; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 31757301
DOI: 10.1016/j.ucl.2019.09.008