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Urology Oct 2020Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of...
Chemoablation is an emerging treatment for urothelial carcinomas. This review provides an overview of the evidence for intracavitary chemoablation in the treatment of urothelial carcinomas. The benefits of such agents include a reduction in morbidity and diseased organ preservation. While numerous agents have shown promise, research is limited due to small patient cohorts, varying follow-up, and no standardized methodology to assess response. Therefore, to date, chemoablation has not been widely adopted. This may change as a novel mitomycin formulation has recently been approved for treating low-grade upper tract urothelial carcinoma. Future studies are ongoing which evaluate other promising chemoablation options in urothelial carcinoma.
Topics: Administration, Intravesical; Antineoplastic Agents; Aziridines; BCG Vaccine; Carcinoma, Transitional Cell; Clinical Trials as Topic; Cystoscopy; Deoxycytidine; Epirubicin; Ethanol; Forecasting; Humans; Indolequinones; Injections, Intralesional; Interferon-alpha; Interleukin-2; Mitomycin; Urinary Bladder Neoplasms; Urothelium; Gemcitabine
PubMed: 32540302
DOI: 10.1016/j.urology.2020.05.066 -
Cancer Medicine Nov 2020Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study... (Meta-Analysis)
Meta-Analysis
Intravesical instillation therapy is the mainstay of prophylaxis of tumor recurrence and progression in non-muscle-invasive bladder cancer. However, there is no study evaluating the superiority of monotherapy. The aim of this study is to compare the efficacy of preventing recurrence and progression of intravesical monotherapies via network meta-analysis (NMA) of randomized controlled trials. Database searches were conducted on Embase, Ovid Medline, Web of Science, ScienceDirect, Cochrane Library, and ClinicalTrials.com from the time of establishment to February 6, 2020. The monotherapies included Bacille Calmette-Guérin (BCG), mitomycin C (MMC), interferon (IFN), adriamycin, epirubicin, gemcitabine (GEM), and thiotepa (THP). A Bayesian consistency network model was generated under a random-effects model. The superiority of therapy was identified based on the surface under the cumulative ranking curve (SUCRA). Fifty-seven studies with 12462 patients are included. NMA shows that GEM (SUCRA = 0.92), BCG (SUCRA = 0.82), and IFN (SUCRA = 0.78) are the top three effective drugs to reduce recurrence. GEM (SUCRA = 0.87) is the most effective therapy to prevent progress, followed by BCG, MMC, THP, and IFN with similar efficacy. Subgroup analysis of pairwise meta-analysis and NMA was performed on publication year, trial initiation year, study origin, center involvement, sample size, drug schedule, tumor characteristics, and trial quality to address confounding factors, which suggests the robustness of the results with stable effect sizes. Network meta-regression also indicates consistent rank by analyzing year, sample size, and quality. Compared with BCG, GEM is also a promising therapy with favorable efficacy to reduce tumor recurrence and progression. IFN and MMC could be alternative therapies for BCG with slightly inferior efficacy in recurrence prevention and similar efficacy in progression prevention. However, the results of this study should be treated with caution since most of the included studies are of moderate to high risk of bias.
Topics: Administration, Intravesical; Antineoplastic Agents; Clinical Trials as Topic; Disease Progression; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Network Meta-Analysis; Progression-Free Survival; Risk Assessment; Risk Factors; Time Factors; Urinary Bladder Neoplasms
PubMed: 33040478
DOI: 10.1002/cam4.3513 -
Frontiers in Surgery 2019To identify different endoscopic techniques for treatment of idiopathic subglottic stenosis (iSGS) and evaluate treatment results. Embase and Cochrane Library were...
To identify different endoscopic techniques for treatment of idiopathic subglottic stenosis (iSGS) and evaluate treatment results. Embase and Cochrane Library were searched for publications on endoscopically treated iSGS. Identified interventions included procedures with cold knife, dilation (rigid or balloon), or laser (CO or Nd:YAG), used in several combinations and supplemented with mitomycin C and/or corticosteroids. Primary endpoint was time interval between successive endoscopic procedures. Secondary endpoints were stenosis recurrence rate, total number of interventions per patient during follow-up, tracheotomy rate, and rate of open surgery. Eighty-six abstracts were reviewed and 15 series were included in the analysis. Mean sample size was 57 subjects (range 10-384, σ 90.84) and mean age was 47 years (range 36-54, σ 4.45). Time interval ranged from 2 to 21 months [weighted mean (WM): 12]. Rate of stenosis recurrence ranged from 40 to 100% (WM: 68%). Mean amount of interventions per patient varied between 1.8 and 8.3 (WM: 3.7). Tracheotomy rate varied between 0 and 26% (WM: 7%) and rate of open surgery varied between 0 and 27% (WM: 10%). Single modality CO lasering showed highest rate of recurrence, highest amount of interventions, and shortest time interval. Combined techniques generated overall better outcomes. A multitude of endoscopic techniques are being used for treating iSGS, all with a considerable recurrence rate. In this review, no superior modality could be identified. Consequently, endoscopic management could be considered a valuable primary treatment option for iSGS, but open surgery still plays an important role.
PubMed: 31998744
DOI: 10.3389/fsurg.2019.00075 -
The Cochrane Database of Systematic... Apr 2020Nasolacrimal duct obstruction (NLDO) is a condition that results in the overflow of tears (epiphora) or infection of the nasolacrimal sac (dacryocystitis). The etiology... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nasolacrimal duct obstruction (NLDO) is a condition that results in the overflow of tears (epiphora) or infection of the nasolacrimal sac (dacryocystitis). The etiology of acquired NLDO is multifactorial and is not fully understood. Dacryocystorhinostomy (DCR) is the surgical correction of NLDO, which aims to establish a new drainage pathway between the lacrimal sac and the nose. The success of DCR is variable; the most common cause of failure is fibrosis and stenosis of the surgical ostium. Antimetabolites such as mitomycin-C (MMC) and 5-fluorouracil (5-FU) have been shown to be safe and effective in reducing fibrosis and improving clinical outcomes in other ophthalmic surgery settings (e.g. glaucoma and cornea surgery). Application of antimetabolites at the time of DCR has been studied, but the utility of these treatments remains uncertain.
OBJECTIVES
Primary objective: To determine if adjuvant treatment with antimetabolites improves functional success in the setting of DCR compared to DCR alone. Secondary objectives: To determine if anatomic success of DCR is increased with the use of antimetabolites, and if the surgical ostium is larger in participants treated with antimetabolites.
SEARCH METHODS
We searched the Cochrane Register for Controlled Trials (CENTRAL) (which contains the Cochrane Eye and Vision Trials Register) (2019, Issue 9), Ovid MEDLINE, Embase.com, PubMed, LILACS (Latin American and Caribbean Health Sciences Literature database), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic searches. We last searched the electronic databases on 6 September 2019.
SELECTION CRITERIA
We only included randomized controlled trials. Eligible studies were those that compared the administration of antimetabolites of any dose and concentration versus placebo or another active treatment in participants with NLDO undergoing primary DCR and reoperation. We only included studies that had enrolled adults 18 years or older. We also included studies that used silicone intubation as part of the DCR procedure.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently screened the search results, assessed risk of bias, and extracted data from the included studies using an electronic data collection form.
MAIN RESULTS
We included 31 studies in the review, of which 23 (1309 participants) provided data relating to our primary and secondary outcomes. Many of the 23 studies evaluated functional success, while others also assessed our secondary outcomes of anatomic success or ostium size, or both. Study characteristics Participant characteristics varied across studies, with the age of participants ranging from 30 to 70 years. Participants were predominantly women. These demographics correspond to those most frequently affected by nasolacrimal duct obstruction. Almost all of the studies utilized MMC as the antimetabolite, with only one using 5-FU. We assessed most trials as at unclear risk of bias for most domains. Conflicts of interest were not frequently reported, although the antimetabolites used are generic medications, and studies were not likely to be conducted for financial interest. Findings Twenty studies provided data on the primary outcome of functional success, of which 7 (356 participants) provided data at 6 months and 14 (909 participants) provided data beyond 6 months. At six months, the results showed no evidence of effect of antimetabolite on functional success (risk ratio (RR) 1.12, 95% confidence interval (CI) 0.98 to 1.29; low-certainty evidence). Beyond six months, the results favored the antimetabolite group (RR 1.15, 95% CI 1.07 to 1.25; moderate-certainty evidence). Fourteen studies reported data on the secondary outcome of anatomic success, of which 4 (306 participants) reported data at 6 months and 12 (831 participants) provided data beyond 6 months. Results at six months showed no evidence of effect of antimetabolite on anatomic success (RR 1.02, 95% CI 0.95 to 1.11; low-certainty evidence). Beyond six months, participants in the antimetabolite group were more likely to achieve anatomic success than those receiving DCR alone (RR 1.09, 95% CI 1.04 to 1.15; moderate-certainty evidence). At six months and beyond six months follow-up, two studies reported mean change in ostium size. We did not conduct meta-analysis for the various follow-up periods due to clinical, methodological, and statistical heterogeneity. However, point estimates from these studies at six months consistently favored participants in the antimetabolite group (low-certainty evidence). Beyond six months, while point estimates from one study favored participants in the antimetabolite group, estimates from another study showed no evidence of a difference between the two groups. The certainty of evidence at both time points was low. Adverse events Adverse events were rare. One study reported that one participant in the MMC group experienced delayed wound healing. Other studies reported no significant adverse events related to the application of antimetabolites.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that application of antimetabolites at the time of DCR increases functional and anatomic success of DCR when patients are followed for more than six months after surgery, but no evidence of a difference at six months, low-certainty of evidence. There is low-certainty evidence that combining antimetabolite with DCR increases the size of the lacrimal ostium at six months. However, beyond six months, the evidence remain uncertain. Adverse effects of the application of antimetabolites were minimal.
Topics: Antimetabolites; Chemotherapy, Adjuvant; Combined Modality Therapy; Dacryocystorhinostomy; Female; Follow-Up Studies; Humans; Lacrimal Duct Obstruction; Male; Mitomycin; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 32259290
DOI: 10.1002/14651858.CD012309.pub2 -
Urologic Oncology Sep 2024Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices... (Review)
Review
INTRODUCTION
Intravesical treatment for non-muscle invasive bladder cancer (NMIBC) aims to reduce recurrences and stop progression. Hyperthermia-enhanced chemotherapy with devices like COMBAT BRS, Unithermia, and BR-TRG-I is a promising alternative to conventional Bacillus de Calmette Guerin (BCG) therapy.
OBJECTIVE
To systematically review the efficacy of hyperthermia generated by conduction devices in the treatment of NMIBC.
MATERIAL AND METHODS
The review followed the preferred reporting items for systematic reviews and meta-analyses guidelines. A search was performed in the PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov databases. Two reviewers independently assessed the eligibility of candidate studies and abstracted data from studies that met the inclusion criteria. The primary endpoint was assessment of recurrence. Secondary objectives included evaluation of treatment progression and safety.
RESULTS
Thirty studies meeting inclusion criteria underwent data extraction. In intermediate-risk NMIBC patients, COMBAT versus mitomycin C (MMC) in normothermia revealed no superiority in reducing recurrence or progression. High-risk NMIBC patients using COMBAT achieved similar or superior outcomes to BCG. BR-TRG-I demonstrated superior results over normothermia in intermediate- and high-risk NMIBC patients. Unithermia proved less effective than BCG in high-risk NMIBC. Progression outcomes were promising with COMBAT and BR-TRG-I, but comprehensive analysis was limited due to inconsistent assessment across studies. Adverse events were primarily mild-moderate, with some device-specific differences.
CONCLUSIONS
Studies on conduction hyperthermia present great variability, which do not allow us to determine the superiority of 1 device over another in terms of recurrence, progression, and/or adverse effects. Further research with consistent administration protocols is crucial for definitive conclusions.
Topics: Humans; Urinary Bladder Neoplasms; Hyperthermia, Induced; Treatment Outcome; Neoplasm Invasiveness; Administration, Intravesical; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38670818
DOI: 10.1016/j.urolonc.2024.03.013 -
PloS One 2021Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure...
BACKGROUND
Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure shows an unsatisfying stricture recurrence rate which could be improved by addition of local therapies.
OBJECTIVES
To provide an overview of both preclinical and clinical studies in order to investigate current level of evidence on the addition of local therapy to improve urethral stricture recurrence rates after endoscopic procedures.
METHODS
We performed a literature search in December 2020 and August 2021 using Cochrane, Embase, PubMed, Scopus and Web of Science and identified articles through combinations of search terms for 'urethral stricture disease', 'stricture formation' and 'local interventions'. We used the SYRCLE, RoB-2 and ROBINS-I tools to assess risk of bias across included studies. We did not perform a meta-analysis due to methodological differences between studies.
RESULTS
We included 32 articles in the qualitative analysis, 20 of which were preclinical studies and 12 clinical studies. Regarding preclinical articles using an animal model, nearly all interventions showed to have a positive effect on either urethral fibrosis, urethral stricture formation and/or fibrotic protein expression levels. Here, immunosuppressants and chemotherapeutics seemed most promising for possible clinical purposes. Regarding clinical studies, mitomycin-C and hyaluronic acid and carboxymethylcellulose showed positive effects on urethral stricture recurrence rates with low to intermediate risk of bias across studies. However, the positive clinical effects of mitomycin-C and steroids seemed to decrease in studies with a longer follow-up time.
CONCLUSION
Although local adjuvant use of mitomycin-C or hyaluronic acid and carboxymethylcellulose may carry clinical potential to improve urethral structure recurrence rates after endoscopic procedures, we believe that a large, well-designed RCT with a yearlong follow-up time is necessary to identify the true clinical value.
Topics: Animals; Extracellular Matrix; Humans; Publication Bias; Risk; Urethral Stricture
PubMed: 34614033
DOI: 10.1371/journal.pone.0258256 -
Medical Archives (Sarajevo, Bosnia and... Jun 2022Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the... (Meta-Analysis)
Meta-Analysis
Comparison Between Intravesical Chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB Alone With Recurrence Rate of Non-Muscle Invasive Bladder Cancer: Meta-Analysis.
BACKGROUND
Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the fourth most common cancer in men and eighth most common women malignancy in the world. This makes bladder cancer a "silent killer" and it needs appropriate treatment planning. Single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB) is recommended by EAU guideline, but its use remains a controversy.
OBJECTIVE
Study aimed to analyze benefit of intravesical chemotherapy following TURB in terms of recurrency of non-muscle invasive bladder cancer (NMIBC).
METHODS
Systematic review and meta-analysis of randomized controlled trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC (pTa-pT1) patients was conducted. Studies searched throughout Medline, PubMed, Embase, and Cochrane in December 2018. Keywords were intravesical chemotherapy, combination, transurethral resection, bladder cancer. Inclusion criteria were RCT studies, subjects in study were treated single immediate chemotherapy instillation after TURB compared to TURB alone in patient with pTa-pT1 urothelial carcinoma of the bladder. Trials with additional treatment prior to first reccurence were not eligible. Studies using recurrence rate as dependent variable. From 361 studies, in total 11 studies were eligible for this meta-analysis.
RESULTS
From those 11 studies, it is shown that intravesical chemotherapy using Epirubicin and Mitomycin-C following TURB showed significant decrease of recurrence rate of bladder cancer even to progression of the disease compared to TURB alone (p<0.05) with pooled Risk Ratio were 0.69 and pooled heterogeneity (I) were 26.6%.
CONCLUSION
This meta-analysis study showed that combination therapy of intravesical chemotherapy after TURB is superior to TURB alone in showing the recurrence rate of NMIBC.
Topics: Administration, Intravesical; Carcinoma, Transitional Cell; Epirubicin; Female; Humans; Male; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms
PubMed: 36200115
DOI: 10.5455/medarh.2022.76.198-201 -
The Journal of Laryngology and Otology Oct 2019Acquired anterior glottic web poses a significant challenge to laryngologists given its propensity to recur following treatment, and there are a wide variety of...
BACKGROUND
Acquired anterior glottic web poses a significant challenge to laryngologists given its propensity to recur following treatment, and there are a wide variety of described techniques.
METHODS
A systematic review of the medical literature was undertaken in order to identify all articles pertaining to the management of acquired anterior glottic web.
RESULTS
Thirteen studies meeting the inclusion criteria were identified and analysed. All were retrospective series, with varying surgical techniques and outcome measures. Only two studies reported on the use of topical mitomycin C.
CONCLUSION
Mucosal graft techniques and keel placement appear to improve success rates, but both carry risks and disadvantages. Based on the available evidence, the use of topical agents such as mitomycin C cannot be recommended in the management of acquired anterior glottic web.
PubMed: 31530291
DOI: 10.1017/S0022215119001920 -
European Journal of Surgical Oncology :... Feb 2021Colorectal cancer (CRC) is a rare condition in the pediatric population, but it is usually associated with worse prognosis compared to the adult population. Surgical...
Colorectal cancer (CRC) is a rare condition in the pediatric population, but it is usually associated with worse prognosis compared to the adult population. Surgical resection is the gold standard and most effective treatment for CRC. Cytoreductive surgery (CRS) and Heated Intra-Peritoneal Chemotherapy (HIPEC) is a feasible option in resectable primary tumour with carcinomatosis and non-evidence of extra-abdominal disease. Although it is very uncommon in children when performed, CRS-HIPEC is based on the description by Sugarbaker et al. and the two most common administrated drugs are Cisplatin and Mitomycin-C. We present a review of the cases found in the literature of peritoneal carcinomatosis from CRC treated with CRS and HIPEC in children. A systematic search was performed in the major databases up to February 2020. We included all the reviews and studies reporting clinical data on pediatric patients with peritoneal colorectal carcinomatosis. Nine cases were extracted from the literature. Patient age was between 11 and 16 years old. All patients underwent neoadjuvant chemotherapy. All patients were treated with HIPEC and the majority of them received a complete cytoreduction (CC-0). At follow-up, three patients were found free from disease with an average time of follow up of 74 weeks (40-100). In 33% of cases, recurrence was described. No postoperative death within 30 days from surgery was observed. CRS and HIPEC can be a feasible option for CRC peritoneal carcinomatosis in children. Because CRC is unusual among the pediatric population, multi-institutional studies should be done to achieve larger cohorts and a more reliable analysis.
Topics: Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Child; Colorectal Neoplasms; Cytoreduction Surgical Procedures; Humans; Peritoneal Neoplasms; Prognosis
PubMed: 32888733
DOI: 10.1016/j.ejso.2020.08.021 -
Eye & Contact Lens Nov 2019To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury.
OBJECTIVES
To evaluate recent studies on available and experimental therapies in preventing or minimizing corneal stromal scarring after injury.
METHODS
We performed an Entrez PubMed literature search using keywords "cornea," "scarring," "haze," "opacity," "ulcer," "treatments," "therapies," "treatment complications," and "pathophysiology" resulting in 390 articles of which 12 were analyzed after filtering, based on English language and publication within 8 years, and curation for relevance by the authors.
RESULTS
The 12 articles selected included four randomized control trials (RCTs) (two were double-blinded placebo-controlled RCTs, one was a prospective partially masked RCT, and one was an open-label RCT), two retrospective observational studies, and six laboratory-based studies including two studies having in vivo and in vitro experiments, one was in vivo study, one was ex vivo study, and the last two were in vitro studies. The current mainstay for preventing or minimizing corneal scarring involves the use of topical corticosteroids and local application of mitomycin C. However, supportive evidence for their use in clinical practice from well-designed RCTs is lacking. Laboratory studies on topical rosiglitazone therapy, vitamin C prophylaxis, gene therapy, and stem cell therapy have shown promising results but have yet to be translated to clinical research.
CONCLUSION
There is a need for more robust randomized controlled trials to support treatments using topical corticosteroids and mitomycin C. Furthermore, their clinical efficacy and safety profile should be compared with new treatments that have shown promising results in the laboratory setting. Ultimately, the goal should be to personalize cornea scarring treatment according to the most effective treatment for the specific underlying pathology.
Topics: Administration, Ophthalmic; Alkylating Agents; Cicatrix; Corneal Injuries; Corneal Stroma; Drug Therapy, Combination; Glucocorticoids; Humans; Mitomycin; Ophthalmic Solutions; Prednisone
PubMed: 30724841
DOI: 10.1097/ICL.0000000000000584