Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.
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ABSTRACT:
SUBMITTER: Queiroga TLO
PROVIDER: S-EPMC6946955 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis.
Queiroga Thereza L O TLO Cataneo Daniele C DC Martins Regina H G RHG Reis Tarcisio A TA Cataneo Antônio J M AJM
International archives of otorhinolaryngology 20191220 1
<b>Introduction</b> Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. <b>Objective</b> To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. <b>Data synthesis</b> 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 res ...[more]
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Project description:Laryngotracheal stenosis is an obstructive respiratory disease that leads to voicing difficulties and dyspnea with potential life-threatening consequences. The majority of incidences are due to iatrogenic etiology from endotracheal tube intubation; however, airway scarring also has idiopathic causes. While recent evidence suggests a microbial contribution to mucosal inflammation, the microbiota associated with different types of stenosis has not been characterized. High-throughput sequencing of the V4 region of the16S rRNA gene was performed to characterize the microbial communities of 61 swab samples from 17 iatrogenic and 10 adult idiopathic stenosis patients. Nonscar swabs from stenosis patients were internal controls, and eight swabs from four patients without stenosis represented external controls. Significant differences in diversity were observed between scar and nonscar samples and among sample sites, with decreased diversity detected in scar samples and the glottis region. Permutational analysis of variance (PERMANOVA) results revealed significant differences in community composition for scar versus nonscar samples, etiology type, sample site, groups (iatrogenic, idiopathic, and internal and external controls), and individual patients. Pairwise Spearman's correlation revealed a strong inverse correlation between Prevotella and Streptococcus among all samples. Finally, bacteria in the family Moraxellaceae were found to be distinctly associated with idiopathic stenosis samples in comparison with external controls. Our findings suggest that specific microbiota and community shifts are present with laryngotracheal stenosis in adults, with members of the family Moraxellaceae, including the known pathogens Moraxella and Acinetobacter, identified in idiopathic scar. Further work is warranted to elucidate the contributing role of bacteria on the pathogenesis of laryngotracheal stenosis.IMPORTANCE The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.
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Project description:ImportanceLaryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS.ObjectiveTo determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro.Design, setting, and participantsThis in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis-derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016.InterventionsTreatment with interferon-γ, 10 ng/mL.Main outcomes and measuresCellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed.ResultsAmong the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, -6515 cells; 95% CI, -10 630 to -2600 cells) to 6 (mean difference, -47 521 cells; 95% CI, -81 285 to -13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts.Conclusions and relevanceInterferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.
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Project description:BackgroundLumbar spinal stenosis (LSS) is caused by neural compression due to narrowing of the lumbar spinal canal or neural foramen. Surgical intervention is a standard treatment for LSS; however, the steep increase in the surgical rate, post-operative complications, and comparatively low long-term satisfaction are considered to be limitations of this surgical approach. Conversely, acupotomy is a minimally invasive technique that combines the effects of conventional acupuncture with micro-incision, which may offer an alternative to surgery for the treatment of LSS. This review was conducted to investigate and critically review the current evidence on the efficacy and safety of acupotomy for LSS.MethodsEleven databases were searched from their respective inception dates to December 28, 2018. Randomized controlled trials (RCTs) comparing acupotomy and wait-list, sham treatment, or active controls were included. The quality of the included studies was assessed using risk-of-bias tool.ResultsSeven RCTs were included in this review and meta-analysis. The methodological quality of the included studies was generally poor. The acupotomy treatment group was associated with significantly lower visual analogue scale scores (range 0∼10) (5 RCTs; mean difference [MD] -1.55, 95% confidence interval [CIs] -2.60 to -0.50; I = 94%) and higher Japanese Orthopedic Association Score (3 RCTs; MD 4.70, 95% CI 3.73 to 5.68; I = 0%) compared to the active control group. In subgroup analysis based on the type of active controls, acupotomy retained significant benefits over lumbar traction and acupuncture, as well as over lumbar traction, spinal decompression, and acupuncture. Safety data were reported in only 1 study, and no adverse events occurred in either the acupotomy or the acupuncture control group.ConclusionAccording to current evidence, acupotomy might be beneficial for treating LSS. Acupotomy showed consistent superiority over lumbar traction, but the results were mixed in comparisons with other interventions, such as spinal decompression and acupuncture. However, the findings should be interpreted cautiously, given the poor methodological quality of the included studies, and potential small-study effects. Further larger, high-quality, rigorous RCTs should be conducted on this topic and rigorous reporting of acupotomy procedures and safety data should be encouraged.
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Project description:ObjectiveTo evaluate the application of the Ologen implant compared to mitomycin C (MMC) on the outcome of trabeculectomy and to examine the balance of risks and benefits.MethodsA systematic literature search (Pubmed, Embase, the Cochrane Library, and the Chinese Biomedicine Database) was performed. Randomized controlled trials comparing the Ologen implant with MMC in trabeculectomy were selected. The efficacy measures were the weighted mean differences (WMDs) for the intraocular pressure reduction (IOPR), the reduction in glaucoma medications, and the relative risks (RRs) for success rates. The tolerability measures were RRs for adverse events. The pooled effects were calculated using the random-effects model.ResultsSeven randomized controlled trials including 227 eyes were included in this meta-analysis. The WMDs of the IOPR comparing the Ologen group with the MMC group were -2.98 (95% Cl: -5.07 to -0.89) at one month, -1.41 (-3.72 to 0.91) at three months, -1.69 (-3.68 to 0.30) at six months, -1.94 (-3.88 to 0.01) at 12 months, and 0.65 (-2.17 to 0.47) at 24 months. There was no statistically significance except at one and 12 months after surgery. No significant difference in the reduction in glaucoma medications or complete and qualified success rates were found. The rates of adverse events also did not differ significantly between Ologen and MMC.ConclusionsThe Ologen implant is comparable with MMC for trabeculectomy in IOP-lowering efficacy, reduction in the number of glaucoma medications, success rates, and tolerability. However, the results should be interpreted cautiously since relevant evidence is still limited, although it is accumulating. Further large-scale, well-designed randomized controlled trials are urgently needed.
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Project description:BACKGROUND:Degenerative lumbar spinal stenosis is a condition related to aging in which structural changes cause narrowing of the central canal and intervertebral foramen. It is currently the leading cause for spinal surgery in patients over 65 years. Interspinous process devices (IPDs) were introduced as a less invasive surgical alternative, but questions regarding safety, efficacy, and cost-effectiveness are still unanswered. OBJECTIVES:The aim of this study was to provide complete and reliable information regarding benefits and harms of IPDs when compared to conservative treatment or decompression surgery and suggest directions for forthcoming RCTs. METHODS:We searched MEDLINE, EMBASE, Cochrane Library, Scopus, and LILACS for randomized and quasi-randomized trials, without language or period restrictions, comparing IPDs to conservative treatment or decompressive surgery in adults with symptomatic degenerative lumbar spine stenosis. Data extraction and analysis were conducted following the Cochrane Handbook. Primary outcomes were pain assessment, functional impairment, Zurich Claudication Questionnaire, and reoperation rates. Secondary outcomes were quality of life, complications, and cost-effectiveness. This systematic review was registered at Prospero (International prospective register of systematic reviews) under number 42015023604. RESULTS:The search strategy resulted in 17 potentially eligible reports. At the end, nine reports were included and eight were excluded. Overall quality of evidence was low. One trial compared IPDs to conservative treatment: IPDs presented better pain, functional status, quality of life outcomes, and higher complication risk. Five trials compared IPDs to decompressive surgery: pain, functional status, and quality of life had similar outcomes. IPD implant presented a significantly higher risk of reoperation. We found low-quality evidence that IPDs resulted in similar outcomes when compared to standard decompression surgery. Primary and secondary outcomes were not measured in all studies and were often published in incomplete form. Subgroup analysis was not feasible. Difficulty in contacting authors may have prevented us of including data in quantitative analysis. CONCLUSIONS:Patients submitted to IPD implants had significantly higher rates of reoperation, with lower cost-effectiveness. Future trials should improve in design quality and data reporting, with longer follow-up periods.
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