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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 -
The Journal of Urology Oct 2023Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).
PURPOSE
Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer.
MATERIALS AND METHODS
This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events.
RESULTS
Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria.
CONCLUSIONS
Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.
Topics: Humans; Male; Female; Prospective Studies; Transurethral Resection of Bladder; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Mitomycin; Administration, Intravesical; Neoplasm Invasiveness; Neoplasm Recurrence, Local
PubMed: 37548555
DOI: 10.1097/JU.0000000000003645 -
The Lancet. Oncology Jun 2020Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical...
Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial.
BACKGROUND
Most patients with low-grade upper tract urothelial cancer are treated by radical nephroureterectomy. We aimed to assess the safety and activity of a non-surgical treatment using instillation of UGN-101, a mitomycin-containing reverse thermal gel.
METHODS
In this open-label, single-arm, phase 3 trial, participants were recruited from 24 academic sites in the USA and Israel. Patients (aged ≥18 years) with primary or recurrent biopsy-proven, low-grade upper tract urothelial cancer (measuring 5-15 mm in maximum diameter) and an Eastern Cooperative Oncology Group performance status score of less than 3 (Karnofsky Performance Status score >40) were registered to receive six instillations of once-weekly UGN-101 (mitomycin 4 mg per mL; dosed according to volume of patient's renal pelvis and calyces, maximum 60 mg per instillation) via retrograde catheter to the renal pelvis and calyces. All patients had a planned primary disease evaluation 4-6 weeks after the completion of initial therapy, in which the primary outcome of complete response was assessed, defined as negative 3-month ureteroscopic evaluation, negative cytology, and negative for-cause biopsy. Activity (complete response, expected to occur in >15% of patients) and safety were assessed by the investigator in all patients who received at least one dose of UGN-101. Data presented are from the data cutoff on May 22, 2019. This study is registered with ClinicalTrials.gov, NCT02793128.
FINDINGS
Between April 6, 2017, and Nov 26, 2018, 71 (96%) of 74 enrolled patients received at least one dose of UGN-101. 42 (59%, 95% CI 47-71; p<0·0001) patients had a complete response at the primary disease evaluation visit. The median follow-up for patients with a complete response was 11·0 months (IQR 5·1-12·4). The most frequently reported all-cause adverse events were ureteric stenosis in 31 (44%) of 71 patients, urinary tract infection in 23 (32%), haematuria in 22 (31%), flank pain in 21 (30%), and nausea in 17 (24%). 19 (27%) of 71 patients had study drug-related or procedure-related serious adverse events. No deaths were regarded as related to treatment.
INTERPRETATION
Primary chemoablation of low-grade upper tract urothelial cancer with intracavitary UGN-101 results in clinically significant disease eradication and might offer a kidney-sparing treatment alternative for these patients.
FUNDING
UroGen Pharma.
Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma; Drug Carriers; Drug Compounding; Female; Humans; Hydrogels; Israel; Kidney Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Grading; Time Factors; Treatment Outcome; United States; Urothelium
PubMed: 32631491
DOI: 10.1016/S1470-2045(20)30147-9 -
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 -
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 -
Cell Communication and Signaling : CCS Jun 2023Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness... (Review)
Review
Cancer stem cells (CSCs) are considered to be responsible for tumor recurrence and metastasis. Therefore, clarification of the mechanisms involved in CSC stemness maintenance and cell fate determination would provide a new strategy for cancer therapy. Unregulated cellular energetics has been accepted as one of the hallmarks of cancer cells, but recent studies have revealed that mitochondrial metabolism can also actively determine CSC fate by affecting nuclear stemness gene expression. Herein, from the perspective of mito-nuclear communication, we review recent progress on the influence of mitochondria on CSC potential from four aspects: metabolism, dynamics, mitochondrial homeostasis, and reactive oxygen species (ROS). Video Abstract.
Topics: Humans; Neoplasm Recurrence, Local; Cell Differentiation; Mitomycin; Mitochondria; Neoplastic Stem Cells; Reactive Oxygen Species
PubMed: 37370081
DOI: 10.1186/s12964-023-01160-x -
Journal Francais D'ophtalmologie Nov 2021Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion... (Review)
Review
Corneal haze represents subepithelial corneal fibrosis, a manifestation of a pathological healing process. It occurs as a result of an epithelial-stromal lesion involving a break in the epithelial barrier. It is an inflammatory response that involves the migration, multiplication and differentiation of keratocytes into mature myofibroblasts, causing loss of corneal transparency. Although it is a transient phenomenon, this complication is feared following refractive photokeratectomy (PRK), because it can cause alterations in the quality of vision, refractive regression and decreased visual acuity. The severity of these symptoms is correlated with the severity of the corneal haze, which can be assessed clinically or by objective means such as corneal densitometry measurement. The frequency and severity of corneal haze increase with the depth of photoablation in PRK and are therefore increased during the treatment of severe ametropia. Considering that no consensus exists, the application of mitomycin C (MMC) intraoperatively and topical corticosteroids postoperatively are conventionally used to inhibit collagen synthesis, sometimes in combination with various protocols depending on the center or surgeon. This review of the literature reports the current knowledge on corneal haze, in order to better understand it and optimise its prevention in the context of a decreased MMC supply, which has occurred in the past and could recur in the future.
Topics: Cornea; Corneal Opacity; Humans; Lasers, Excimer; Mitomycin; Photorefractive Keratectomy
PubMed: 34538661
DOI: 10.1016/j.jfo.2021.05.006