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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 -
The Cochrane Database of Systematic... Jun 2021It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or recurrent setting following transurethral resection of a bladder tumor. This is an update of a Cochrane Review first published in 2012. Since that time, several randomized controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for NMIBC.
SEARCH METHODS
We performed a comprehensive literature search of the Cochrane Library, MEDLINE, Embase, four other databases, trial registries, and conference proceedings to 11 September 2020, with no restrictions on the language or status of publication.
SELECTION CRITERIA
We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the included studies and extracted data for the primary outcomes: time to recurrence, time to progression, grade III to V adverse events determined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), and the secondary outcomes: time to death from bladder cancer, time to death from any cause, grade I or II adverse events determined by the CTCAE v5.0 and disease-specific quality of life. We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE.
MAIN RESULTS
We included seven studies with 1222 participants with NMIBC across five comparisons. This abstract focuses on the primary outcomes of the three most clinically relevant comparisons. 1. Gemcitabine versus saline: based on two years' to four years' follow-up, gemcitabine may reduce the risk of recurrence over time compared to saline (39% versus 47% recurrence rate, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54 to 1.09; studies = 2, participants = 734; I = 49%; low-certainty evidence), but the CI included the possibility of no effect. Gemcitabine may result in little to no difference in the risk of progression over time compared to saline (4.6% versus 4.8% progression rate, HR 0.96, 95% CI 0.19 to 4.71; studies = 2, participants = 654; I = 53%; low-certainty evidence). Gemcitabine may result in little to no difference in the CTCAE grade III to V adverse events compared to saline (5.9% versus 4.7% adverse events rate, risk ratio [RR] 1.26, 95% CI 0.58 to 2.75; studies = 2, participants = 668; I = 24%; low-certainty evidence). 2. Gemcitabine versus mitomycin: based on three years' follow-up (studies = 1, participants = 109), gemcitabine may reduce the risk of recurrence over time compared to mitomycin (17% versus 40% recurrence rate, HR 0.36, 95% CI 0.19 to 0.69; low-certainty evidence). Gemcitabine may reduce the risk of progression over time compared to mitomycin (11% versus 18% progression rate, HR 0.57, 95% CI 0.32 to 1.01; low-certainty evidence), but the CI included the possibility of no effect. We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to mitomycin (RR 0.51, 95% CI 0.13 to 1.93; very low-certainty evidence). The analysis was only based on recurrent NMIBC. 3. Gemcitabine versus Bacillus Calmette-Guérin (BCG) for recurrent (one-course BCG failure) high-risk NMIBC: based on 6 months' to 22 months' follow-up (studies = 1, participants = 80), gemcitabine may reduce the risk of recurrence compared to BCG (41% versus 97% recurrence rate, HR 0.15, 95% CI 0.09 to 0.26; low-certainty evidence) and progression over time (16% versus 33% progression rate, HR 0.45, 95% CI 0.27 to 0.76; low-certainty evidence). We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to BCG (RR 1.00, 95% CI 0.21 to 4.66; very low-certainty evidence). In addition, the review provides information on the comparison of gemcitabine versus BCG and gemcitabine versus one-third dose BCG. AUTHORS' CONCLUSIONS: Based on findings of this review, gemcitabine may have a more favorable impact on recurrence and progression-free survival than mitomycin but we are very uncertain as to how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high risk disease who have previously failed BCG. The underlying low- to very low-certainty evidence indicates that our confidence in these results is limited; the true effects may be substantially different from these findings; therefore, better quality studies are needed.
Topics: Adjuvants, Immunologic; Administration, Intravesical; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; BCG Vaccine; Bias; Cause of Death; Confidence Intervals; Deoxycytidine; Disease Progression; Drug Administration Schedule; Humans; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Saline Solution; Urinary Bladder Neoplasms; Gemcitabine
PubMed: 34125951
DOI: 10.1002/14651858.CD009294.pub3 -
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 -
Ophthalmology Dec 2021To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG). (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG).
DESIGN
One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe.
PARTICIPANTS
Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy.
METHODS
Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes).
MAIN OUTCOME MEASURES
The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use and adverse events.
RESULTS
Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation, -12.34 decibels [dB]). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% vs. 72.7%, respectively; P < 0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1 ± 4.9 mmHg at baseline to 14.3 ± 4.3 mmHg (-29.1%; P < 0.01) at year 1, with a mean of 0.6 ± 1.1 glaucoma medications (baseline 3.1 ± 1.0; P < 0.01). In the trabeculectomy group, mean IOP decreased from 21.1 ± 5.0 mmHg to 11.1 ± 4.3 mmHg (-45.4%; P < 0.01), with a mean of 0.3 ± 0.9 glaucoma medications (baseline 3.0 ± 0.9; P < 0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P < 0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% vs. 28.9%; P < 0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients.
CONCLUSIONS
Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.
Topics: Adult; Aged; Aged, 80 and over; Alkylating Agents; Antihypertensive Agents; Female; Follow-Up Studies; Glaucoma Drainage Implants; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Mitomycin; Prospective Studies; Prosthesis Implantation; Single-Blind Method; Tonometry, Ocular; Trabeculectomy; Treatment Outcome; Visual Acuity; Visual Fields
PubMed: 34051211
DOI: 10.1016/j.ophtha.2021.05.023 -
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 -
Cancers Mar 2021Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy... (Review)
Review
Prior to the 1980s, the primary management of localized anal cancer was surgical resection. Dr. Norman Nigro and colleagues introduced neoadjuvant chemoradiotherapy prior to abdominoperineal resection. Chemoradiotherapy 5-fluorouracil and mitomycin C afforded patients complete pathologic response and obviated the need for upfront surgery. More recent studies have attempted to alter or exclude chemotherapy used in the Nigro regimen to mitigate toxicity, often with worse outcomes. Reductions in acute adverse effects have been associated with marked advancements in radiotherapy delivery using intensity-modulated radiation therapy (IMRT) and image-guidance radiation delivery, resulting in increased tolerance to greater radiation doses. Ongoing trials are attempting to improve IMRT-based treatment of locally advanced disease with efforts to increase personalized treatment. Studies are also examining the role of newer treatment modalities such as proton therapy in treating anal cancer. Here we review the evolution of radiotherapy for anal cancer and describe recent advances. We also elaborate on radiotherapy's role in locally persistent or recurrent anal cancer.
PubMed: 33801992
DOI: 10.3390/cancers13061208 -
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