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Systematic Reviews Mar 2023Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities... (Review)
Review
BACKGROUND
Keloids are pathologic scars that pose a significant functional and cosmetic burden. They are challenging to treat, despite the multitude of treatment modalities currently available.
OBJECTIVE
The aim of this study was to conduct an evidence-based review of all prospective data regarding keloid treatments published between 2010 and 2020.
METHODS
A systematic literature search of PubMed (National Library of Medicine), Embase (Elsevier), and Cochrane Library (Wiley) was performed in November of 2020. Search strategies with the keywords "keloid" and "treatment" were performed by a medical librarian. The search was limited to prospective studies that were peer-reviewed, reported on clinical outcomes of keloid therapies, and were published in the English language between January 1, 2010, and November 24, 2020.
RESULTS
A total of 3462 unique citations were identified, of which 108 studies met inclusion criteria. Current literature supports silicone gel or sheeting with corticosteroid injections as first-line therapy for keloids. Adjuvant intralesional 5-fluorouracil (5-FU), bleomycin, or verapamil can be considered, although mixed results have been reported with each. Laser therapy can be used in combination with intralesional corticosteroids or topical steroids with occlusion to improve drug penetration. Excision of keloids with immediate post-excision radiation therapy is an effective option for recalcitrant lesions. Finally, silicone sheeting and pressure therapy have evidence for reducing keloid recurrence.
CONCLUSIONS
This review was limited by heterogeneity of subject characteristics and study outcome measures, small sample sizes, and inconsistent study designs. Larger and more robust controlled studies are necessary to further understand the variety of existing and emerging keloid treatments, including corticosteroids, cryotherapy, intralesional injections, lasers, photodynamic therapy, excision and radiation, pressure dressings, and others.
Topics: Humans; Prospective Studies; Keloid; Fluorouracil; Adrenal Cortex Hormones; Verapamil; Treatment Outcome
PubMed: 36918908
DOI: 10.1186/s13643-023-02192-7 -
The Cochrane Database of Systematic... Apr 2020Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid, including administration of a pleurodesis agent (via a chest tube or thoracoscopy) or placement of an indwelling pleural catheter (IPC). This is an update of a review published in Issue 5, 2016, which replaced the original, published in 2004.
OBJECTIVES
To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success and to quantify differences in patient-reported outcomes and adverse effects between interventions.
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and three other databases to June 2019. We screened reference lists from other relevant publications and searched trial registries.
SELECTION CRITERIA
We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE, comparing types of sclerosant, mode of administration and IPC use.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data on study design, characteristics, outcome measures, potential effect modifiers and risk of bias. The primary outcome was pleurodesis failure rate. Secondary outcomes were adverse events, patient-reported breathlessness control, quality of life, cost, mortality, survival, duration of inpatient stay and patient acceptability. We performed network meta-analyses of primary outcome data and secondary outcomes with enough data. We also performed pair-wise meta-analyses of direct comparison data. If we deemed interventions not jointly randomisable, or we found insufficient available data, we reported results by narrative synthesis. For the primary outcome, we performed sensitivity analyses to explore potential causes of heterogeneity and to evaluate pleurodesis agents administered via a chest tube only. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We identified 80 randomised trials (18 new), including 5507 participants. We found all except three studies at high or unclear risk of bias for at least one domain. Due to the nature of the interventions, most studies were unblinded. Pleurodesis failure rate We included 55 studies of 21 interventions in the primary network meta-analysis. We estimated the rank of each intervention's effectiveness. Talc slurry (ranked 6, 95% credible interval (Cr-I) 3 to 10) is an effective pleurodesis agent (moderate certainty for comparison with placebo) and may result in fewer pleurodesis failures than bleomycin and doxycycline (bleomycin versus talc slurry: odds ratio (OR) 2.24, 95% Cr-I 1.10 to 4.68; low certainty; ranked 11, 95% Cr-I 7 to 15; doxycycline versus talc slurry: OR 2.51, 95% Cr-I 0.81 to 8.40; low certainty; ranked 12, 95% Cr-I 5 to 18). There is little evidence of a difference between the pleurodesis failure rate of talc poudrage and talc slurry (OR 0.50, 95% Cr-I 0.21 to 1.02; moderate certainty). Evidence for any difference was further reduced when restricting analysis to studies at low risk of bias (defined as maximum one high risk domain in the risk of bias assessment) (pleurodesis failure talc poudrage versus talc slurry: OR 0.78, 95% Cr-I 0.16 to 2.08). IPCs without daily drainage are probably less effective at obtaining a definitive pleurodesis (cessation of pleural fluid drainage facilitating IPC removal) than talc slurry (OR 7.60, 95% Cr-I 2.96 to 20.47; rank = 18/21, 95% Cr-I 13 to 21; moderate certainty). Daily IPC drainage or instillation of talc slurry via IPC are likely to reduce pleurodesis failure rates. Adverse effects Adverse effects were inconsistently reported. We performed network meta-analyses for the risk of procedure-related fever and pain. The evidence for risk of developing fever was of low certainty, but suggested there may be little difference between interventions relative to talc slurry (talc poudrage: OR 0.89, 95% Cr-I 0.11 to 6.67; bleomycin: OR 2.33, 95% Cr-I 0.45 to 12.50; IPCs: OR 0.41, 95% Cr-I 0.00 to 50.00; doxycycline: OR 0.85, 95% Cr-I 0.05 to 14.29). Evidence also suggested there may be little difference between interventions in the risk of developing procedure-related pain, relative to talc slurry (talc poudrage: OR 1.26, 95% Cr-I 0.45 to 6.04; very-low certainty; bleomycin: OR 2.85, 95% Cr-I 0.78 to 11.53; low certainty; IPCs: OR 1.30, 95% Cr-I 0.29 to 5.87; low certainty; doxycycline: OR 3.35, 95% Cr-I 0.64 to 19.72; low certainty). Patient-reported control of breathlessness Pair-wise meta-analysis suggests there is likely no difference in breathlessness control, relative to talc slurry, of talc poudrage ((mean difference (MD) 4.00 mm, 95% CI -6.26 to 14.26) on a 100 mm visual analogue scale for breathlessness; studies = 1; participants = 184; moderate certainty) and IPCs without daily drainage (MD -6.12 mm, 95% CI -16.32 to 4.08; studies = 2; participants = 160; low certainty). Overall mortality There may be little difference between interventions when compared to talc slurry (bleomycin and IPC without daily drainage; low certainty) but evidence is uncertain for talc poudrage and doxycycline. Patient acceptability Pair-wise meta-analysis demonstrated that IPCs probably result in a reduced risk of requiring a repeat invasive pleural intervention (OR 0.25, 95% Cr-I 0.13 to 0.48; moderate certainty) relative to talc slurry. There is likely little difference in the risk of repeat invasive pleural intervention with talc poudrage relative to talc slurry (OR 0.96, 95% CI 0.59 to 1.56; moderate certainty).
AUTHORS' CONCLUSIONS
Based on the available evidence, talc poudrage and talc slurry are effective methods for achieving a pleurodesis, with lower failure rates than a number of other commonly used interventions. IPCs provide an alternative approach; whilst associated with inferior definitive pleurodesis rates, comparable control of breathlessness can probably be achieved, with a lower risk of requiring repeat invasive pleural intervention. Local availability, global experience of agents and adverse events (which may not be identified in randomised trials) and patient preference must be considered when selecting an intervention. Further research is required to delineate the roles of different treatments according to patient characteristics, such as presence of trapped lung. Greater attention to patient-centred outcomes, including breathlessness, quality of life and patient preference is essential to inform clinical decision-making. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.
Topics: Adult; Bleomycin; Doxycycline; Dyspnea; Fever; Humans; Iodine; Network Meta-Analysis; Pleural Effusion, Malignant; Pleurodesis; Quinacrine; Randomized Controlled Trials as Topic; Talc; Treatment Failure
PubMed: 32315458
DOI: 10.1002/14651858.CD010529.pub3 -
Interventional Neuroradiology : Journal... Apr 2021Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such...
BACKGROUND
Orbital and peri-orbital venolymphatic malformations (VLM) are low flow vascular malformations. Intralesional bleomycin is now commonly being used to treat such malformations.
OBJECTIVE
The purpose of this systematic review is to synthesize evidence on the safety and efficacy of bleomycin/pingyangmycin sclerotherapy for the treatment of orbital and peri-orbital VLM.
METHODS
We searched Medline, Embase, Scopus and Cochrane database for studies reporting outcomes of bleomycin/pingyangmycin sclerotherapy for orbital and peri-orbital VLM between 1974 to April 5th, 2019. Nine retrospective cohort studies enrolling 132 patients were included. Two reviewers independently screened and extracted data and assessed the risk of bias. Predefined outcome measures were subjective and objective reduction of the lesion and associated complications.
RESULTS
Subjective reduction of the lesions was seen in 96.2% of the studies. Objective reduction of the lesion and symptomatic improvement were reported in 91.6 and 95% of the studies respectively. Non responders were 9.0%. Minor adverse events were reported in 18.1% of the studies. Major complications like pulmonary toxicity or pulmonary fibrosis was not encountered in any of the included studies. Quality of evidence was generally low.
CONCLUSION
Bleomycin/pingyangmycin sclerotherapy is very effective and relatively safe for the treatment of orbital and periorbital VLM and is not associated with any major side effects including pulmonary fibrosis. The systematic review is limited mainly due to low quality of the included studies with retrospective design.
Topics: Bleomycin; Humans; Injections, Intralesional; Retrospective Studies; Sclerosing Solutions; Sclerotherapy; Treatment Outcome; Vascular Malformations
PubMed: 33175616
DOI: 10.1177/1591019920972514 -
Drug Delivery and Translational Research Jun 2023Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and... (Review)
Review
Needle-free jet injectors are used for the intralesional treatment of various dermatological indications. However, a systematic review that evaluates the efficacy and safety of these treatments has not been published. The objectives of this study are to evaluate the efficacy and safety of needle-free jet injections for dermatological indications and to provide evidence-based treatment recommendations. An electronic literature search was conducted in April 2022. Two reviewers independently selected studies based on predefined criteria and performed a methodological quality assessment using the Cochrane Collaborations risk-of-bias 2.0 assessment tool and Newcastle-Ottawa Scale. Thirty-seven articles were included, involving 1911 participants. Dermatological indications included scars, alopecia areata, hyperhidrosis, nail diseases, non-melanoma skin cancer, common warts, local anesthesia, and aesthetic indications. Keloids and other types of scars (hypertrophic, atrophic, and burn scars) were investigated most frequently (n = 7). The included studies reported favorable efficacy and safety outcomes for intralesional jet injector-assisted treatment with triamcinolone acetonide/hexacetonide, 5-fluorouracil, bleomycin, or hyaluronic acid. Two high-quality studies showed good efficacy and tolerability of intralesional jet injections with a combination of 5-fluorouracil and triamcinolone acetonide in hypertrophic scars and with saline in boxcar and rolling acne scars. No serious adverse reactions and good tolerability were reported in the included studies. Overall, the methodological quality of the included studies was low. Limited evidence suggests that needle-free jet injector-assisted intralesional treatment is efficacious and safe for hypertrophic and atrophic acne scars. More well-powered RCTs investigating the efficacy and safety of jet injector treatment in dermatology are warranted to make further evidence-based recommendations.
Topics: Humans; Triamcinolone Acetonide; Dermatology; Keloid; Fluorouracil; Acne Vulgaris; Treatment Outcome
PubMed: 36884194
DOI: 10.1007/s13346-023-01295-x -
Brazilian Journal of Otorhinolaryngology 2023At present, bleomycin has been widely used in the treatment of Lymphatic Malformations (LMs). This study aims to perform a meta-analysis to investigate the effectiveness... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
At present, bleomycin has been widely used in the treatment of Lymphatic Malformations (LMs). This study aims to perform a meta-analysis to investigate the effectiveness and influencing factors of bleomycin in the treatment of LMs.
METHODS
We conducted a systematic review and meta-analysis to clarify the relationship between bleomycin and LMs. PubMed, ISI Web of Science and MEDLINE were searched.
RESULTS
A total of 21 studies (including 428 cases) about bleomycin sclerotherapy for LMs were included in the current meta-analyses. We calculated pooled effective rate and 95% Confidence Interval (95% CI) using random effects model to evaluate the relations between bleomycin and LMs. The results suggested that the effective rate of bleomycin was the combined effective rate was 84.0% (95% CI 0.81‒0.87) and ranged from 39% (95% CI 0.22‒0.56) to 94% (95% CI 0.87-1.02). The heterogeneity among the studies was substantial (I=61.7%, p= 0.000). In subgroup analyses, it was observed that among retrospective study and prospective study, the estimated effective rate was 80.0% (95% CI 0.76‒0.84) and 91.0% (95% CI 0.85‒0.97), respectively. In terms of the dosage, the combined effective rates of weight-based group and fixed-dose group were 86% (95% CI 0.83‒0.90) and 74.0% (95% CI 0.66‒0.82), respectively. There was no significant publication bias in Egger's test (p=0.059, 95% CI -3.81 to 0.082), but Begg's test did (p=0.023), and the funnel plot is asymmetric.
CONCLUSION
Our study suggested that bleomycin was safe and effective in the treatment of LMs and was primarily dose dependent.
Topics: Humans; Sclerotherapy; Bleomycin; Retrospective Studies; Prospective Studies; Treatment Outcome; Lymphatic Abnormalities
PubMed: 37423005
DOI: 10.1016/j.bjorl.2023.101285 -
Cancers Apr 2021Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative... (Review)
Review
Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma.
PubMed: 33919139
DOI: 10.3390/cancers13091993 -
Journal of Clinical and Experimental... Nov 2019The aim of this study was to systematically review the literature for studies that investigated the effects of sclerosing agents on head and neck hemangiomas. (Review)
Review
BACKGROUND
The aim of this study was to systematically review the literature for studies that investigated the effects of sclerosing agents on head and neck hemangiomas.
MATERIAL AND METHODS
Clinical trials, cohort studies, and descriptive studies were considered eligible and selected in a two-phase process. Six main electronic databases, in addition to three grey literature databases, were searched. Risk of bias (RoB) was assessed using the "Meta-Analysis of Statistics Assessment and Review Instrument" checklist. From fifty-six considered eligible, five were finally included.
RESULTS
One article were judged at low, one at moderate, and three at high RoB. The sclerosing agents investigated were sodium tetradecyl sulphate (n=2), ethanolamine oleate (n=1), pingyangmycin (n=1) and bleomycin (n=1). Overall, good results were achieved on the treatment of head and neck hemangiomas with intralesional sclerotherapy. Most commonly reported adverse effects included pain, swelling, fever, necrosis, transient facial palsy, and anorexia.
CONCLUSIONS
Considering the limited number of included studies, intralesional sclerotherapy on the management of HN hemangiomas presented overall good results with minor adverse reactions, especially in regards to smaller lesions. Sclerotherapy, sclerosing solutions, vascular neoplasms, hemangioma.
PubMed: 31700578
DOI: 10.4317/jced.56143 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
Stem Cell Research & Therapy Aug 2021Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from... (Review)
Review
Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (- 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.
Topics: Bleomycin; COVID-19; Humans; Idiopathic Pulmonary Fibrosis; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Quality of Life
PubMed: 34420515
DOI: 10.1186/s13287-021-02551-y -
Skin Health and Disease Jun 2022While treatment options exist for solitary or disseminated Kaposi sarcoma (KS) disease, there are currently no standardized clinical treatment guidelines for cutaneous...
BACKGROUND
While treatment options exist for solitary or disseminated Kaposi sarcoma (KS) disease, there are currently no standardized clinical treatment guidelines for cutaneous KS.
OBJECTIVE
This systematic review seeks to identify safe and effective topical treatments for cutaneous KS lesions.
METHODS
We conducted a systematic review using peer-reviewed articles from January 1970 to September 2021 published in the PubMed/MEDLINE and EMBASE databases.
RESULTS
From the initial search that yielded 590 studies, 34 met the inclusion criteria and were selected. Of the 34 studies, seven were clinical trials, 26 were case reports/series and one was a multicentre study. A total of 634 patients were included in our review. The three most common topical treatments used for cutaneous KS were imiquimod, alitretinoin and timolol. Topical alitretinoin was used in three case reports and three clinical trials. Topical imiquimod was used in eight case reports, one prospective phase II cohort study and one comparative single-blinded non-controlled clinical study. Topical timolol was used in nine case reports/series. Our review also identified reports of less widely used topical treatments for cutaneous KS. These include topical diphencyprone (DPCP), all--retinoic-acid, rapamycin and bleomycin-dimethylsulfoxide (BLM-DMSO) which achieved variable response rates but have not been widely studied.
CONCLUSION
Topical alitretinoin, imiquimod and timolol demonstrated positive responses for cutaneous KS and the treatments were well tolerated. These three topical treatment modalities could be considered by clinicians when treating cutaneous KS.
PubMed: 35677916
DOI: 10.1002/ski2.107