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Photodiagnosis and Photodynamic Therapy Sep 2022Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX... (Review)
Review
Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX during its formation is almost painless and as effective. Recent studies suggest that this gentle simultaneous activation can be performed indoors by replacing daylight with a suitable light source. We aimed to systematically review efficacy and tolerability of indoor gentle PDT of AKs using various light sources. We systematically searched MEDLINE, Embase, and the Cochrane Library for clinical studies of treatment efficacy or adverse events. Indoor gentle PDT consists of application of methyl aminolevulinate or 5-aminolevulinic acid on the skin prior to long time illumination, starting no later than one hour after application. Fifteen studies met the selection criteria, enrolling 518 patients with more than 5,000 AKs undergoing indoor gentle PDT. The studies mainly included thin AKs comprised of 8 uncontrolled studies and 7 randomized controlled trials (RCT) of which 3 were designed as non-inferiority RCTs. Results from both controlled and uncontrolled trials indicated good treatment tolerability with very low pain scores like those of daylight PDT. Reduction of AK lesions 3 months after indoor gentle PDT in RCTs ranged from 52% to 79%, which is comparable to classic and daylight PDT. All 3 non-inferiority RCTs reported that indoor gentle PDT was non-inferior in terms of efficacy to classic PDT. The included studies used varying treatment protocols with different pretreatments, incubation time, light sources, and irradiation time. No standard protocol for indoor gentle PDT exists yet.
Topics: Aminolevulinic Acid; Humans; Keratosis, Actinic; Photochemotherapy; Photosensitizing Agents; Sunlight; Treatment Outcome
PubMed: 35421601
DOI: 10.1016/j.pdpdt.2022.102858 -
Reviews in Endocrine & Metabolic... Jun 2022Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is... (Review)
Review
Fluorescence-guided detection of pituitary neuroendocrine tumor (PitNET) tissue during endoscopic transsphenoidal surgery available agents, their potential, and technical aspects.
Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future.
Topics: Adenoma; Fluorescent Dyes; Humans; Indocyanine Green; Neuroendocrine Tumors; Pituitary Neoplasms; Retrospective Studies
PubMed: 35344185
DOI: 10.1007/s11154-022-09718-9 -
Journal of Clinical Medicine Mar 2022Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for...
Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Actinic keratosis (AK) is a chronic skin condition that may progress to cutaneous squamous cell carcinoma. We conducted a systematic review of efficacy and safety for key treatments for AK of the face and scalp, including the novel 5-day tirbanibulin 1% ointment. MEDLINE, PubMed, Embase, Cochrane Library, clinical trial registries and regulatory body websites were searched. The review included 46 studies, of which 35 studies included interventions commonly used in Europe and were sufficiently homogenous to inform a Bayesian network meta-analysis of complete clearance against topical placebo or vehicle. The network meta-analysis revealed the following odds ratios and 95% credible intervals: cryosurgery 13.4 (6.2-30.3); diclofenac 3% 2.9 (1.9-4.3); fluorouracil 0.5% + salicylic acid 7.6 (4.6-13.5); fluorouracil 4% 30.3 (9.1-144.7); fluorouracil 5% 35.0 (10.2-164.4); imiquimod 3.75% 8.5 (3.5-22.4); imiquimod 5% 17.9 (9.1-36.6); ingenol mebutate 0.015% 12.5 (8.1-19.9); photodynamic therapy with aminolevulinic acid 24.1 (10.9-52.8); photodynamic therapy with methyl aminolevulinate 11.7 (6.0-21.9); tirbanibulin 1% 11.1 (6.2-20.9). Four sensitivity analyses, from studies assessing efficacy after one treatment cycle only, for ≤25 cm treatment area, after 8 weeks post-treatment, and with single placebo/vehicle node confirmed the findings from the base case. Safety outcomes were assessed qualitatively. These results suggest that tirbanibulin 1% offers a novel treatment for AK, with a single short treatment period, favourable safety profile and efficacy, in line with existing topical treatments available in Europe.
PubMed: 35329979
DOI: 10.3390/jcm11061654 -
Journal of Clinical and Experimental... Mar 2022Dentists now have access to a wide range of unique treatment methods as a result of substantial scientific and technological breakthroughs in the field of dentistry.... (Review)
Review
BACKGROUND
Dentists now have access to a wide range of unique treatment methods as a result of substantial scientific and technological breakthroughs in the field of dentistry. Photodynamic therapy (PDT) is a non-invasive treatment procedure that use photosensitizers, a specific wavelength of light, and the production of singlet oxygen and reactive oxygen species (ROS) to kill undesired eukaryotic cells (such as oral tumors) and harmful microbes. In several disciplines of dentistry, it is seen as a valid therapeutic option. The purpose of this study was to examine the effectiveness and side effects of PDT in the treatment of oral premalignant lesions.
MATERIAL AND METHODS
Three search engines (PubMed, ISI Web of Science, and the Cochrane Library) were used to conduct a systematic review using the phrases photodynamic therapy and PDT in combination with other terms. To define our study eligibility criteria, we used the Population, Intervention and Comparison, Outcomes, and Study design technique.
RESULTS
Initial results were 33. Definitely, 18 studies met our selection criteria.
CONCLUSIONS
Our analysis suggests ALA- PDT as a promising therapeutic modality for OEL lesions which should be treated first with the topical ALA-PDT using either the LED or laser light for successful clinical outcome for OEL lesions. Photodynamic Therapy, Photosensitizer, Aminolevulinic Acid (ALA), Methylene Blue (MB), Toludine Blue, Oral Leukoplakia, Oral Erythroplakia, Oral Verrucous hyperplasia, Oral Lichen Planus.
PubMed: 35317296
DOI: 10.4317/jced.59348 -
Frontiers in Oncology 2022Several studies have confirmed the impact of 5-aminolevulinic acid (5-ALA) on the extent of resection in newly diagnosed glioblastoma (GBM). However, there are...
BACKGROUND
Several studies have confirmed the impact of 5-aminolevulinic acid (5-ALA) on the extent of resection in newly diagnosed glioblastoma (GBM). However, there are controversies on the 5-ALA fluorescence status in recurrent GBM surgery, with specific reference to pseudoprogression or radionecrosis; therefore, the safety and accuracy of surgical planning in 5-ALA-assisted procedures in the recurrent context are still unclear.
MATERIALS AND METHODS
This is a systematic review and meta-analysis of comparative studies on the use of 5-ALA in newly diagnosed and recurrent GBM, consistently conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Data on fluorescence status and correlation between fluorescence and histological findings were collected. We performed a meta-analysis of proportions to estimate the pooled rates of each outcome.
RESULTS
Three online medical databases (PubMed, Scopus, Cochrane Library) were screened, 448 articles were evaluated, and 3 papers were finally included for data analysis. Fluorescence rate was not different between newly diagnosed and recurrent GBM [p = 0.45; odds ratio (OR): 1.23; 95% CI: 0.72-2.09; I = 0%], while the rate of 5-ALA fluorescence-positive areas not associated with histological findings of GBM cells was higher in recurrent GBM (p = 0.04; OR: 0.24; 95% CI: 0.06-0.91; I = 19%). Furthermore, there were no cases of radionecrosis in false-positive samples, while inflammation and signs of pseudoprogression were found in 81.4% of the cases.
DISCUSSION AND CONCLUSIONS
Therefore, a robust awareness of 5-ALA potentialities and pitfalls in recurrent GBM surgery should be considered for a cognizant surgical strategy. Further clinical trials could confirm the results of the present meta-analysis.
PubMed: 35252015
DOI: 10.3389/fonc.2022.848036 -
Dermatology and Therapy Jan 2022Microneedling (MN) is a minimally invasive procedure involving the induction of percutaneous wounds with medical-grade needles. In this literature review, we investigate... (Review)
Review
INTRODUCTION
Microneedling (MN) is a minimally invasive procedure involving the induction of percutaneous wounds with medical-grade needles. In this literature review, we investigate clinical data on MN for the treatment of hair loss disorders.
METHODS
A literature search was conducted through PubMed up to November 2021 to identify original articles evaluating the use of MN on hair loss disorders. The database was searched using the following keywords: "microneedling," "micro needling," "micro needle," "microneedle," "needle," "dermaroller" and "alopecia," "hair loss," "alopecia," "areata," "cicatricial," or "effluvium," RESULTS: A total of 22 clinical studies featuring 1127 subjects met our criteria for inclusion. Jadad scores ranged from 1 to 3, with a mean of 2. As an adjunct therapy, MN improved hair parameters across genders and a range of hair loss types, severities, needling devices, needling depths of 0.50-2.50 mm, and session frequencies from once weekly to monthly. Across 17 investigations totaling 911 androgenic alopecia (AGA) subjects, MN improved hair parameters when paired with 5% minoxidil, growth factor solutions, and/or platelet-rich plasma (PRP) topicals, or when introduced to subjects whose hair count changes had plateaued for ≥ 6 months on other treatments. Across four investigations on 201 alopecia areata (AA) subjects, MN improved hair parameters as a standalone therapy versus cryotherapy, as an adjunct to 5-aminolevulinic acid and photodynamic therapy, and equivalently when paired with topical PRP versus carbon dioxide laser therapy with topical PRP. Across 657 subjects receiving MN, no serious adverse events were reported.
CONCLUSIONS
Clinical studies demonstrate generally favorable results for MN as an adjunct therapy for AGA and AA. However, data are of relatively low quality. Significant heterogeneity exists across interventions, comparators, and MN procedures. Large-scale randomized controlled trials are recommended to discern the effects of MN as a standalone and adjunct therapy, determine best practices, and establish long-term safety.
PubMed: 34854067
DOI: 10.1007/s13555-021-00653-2 -
Pharmaceuticals (Basel, Switzerland) Mar 20215-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in... (Review)
Review
5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.
PubMed: 33800109
DOI: 10.3390/ph14030229 -
BJU International Sep 2021To assess whether single immediate intravesical chemotherapy (SIIC) adds value to bladder tumour management in combination with novel optical techniques: enhanced... (Meta-Analysis)
Meta-Analysis
Impact of enhanced optical techniques at time of transurethral resection of bladder tumour, with or without single immediate intravesical chemotherapy, on recurrence rate of non-muscle-invasive bladder cancer: a systematic review and network meta-analysis of randomized trials.
OBJECTIVE
To assess whether single immediate intravesical chemotherapy (SIIC) adds value to bladder tumour management in combination with novel optical techniques: enhanced transurethral resection of bladder tumour (TURBT).
METHODS
A systematic search was performed using the PubMed and Web of Science databases in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for network meta-analyses. Studies that compared recurrence rates among intervention groups (TURBT with photodynamic diagnosis [PDD] ± SIIC, narrow-band imaging [NBI] ± SIIC, or white-light cystoscopy [WLC] + SIIC) and a control group (TURBT with WLC alone) were included. We used the Bayesian approach in the network meta-analysis.
RESULTS
Twenty-two studies (n = 4519) met our eligibility criteria. Out of six different interventions including three different optical techniques, compared to WLC alone, blue-light cystoscopy (BLC) plus SIIC (odds ratio [OR] 0.349, 95% credible interval [CrI] 0.196-0.601) and BLC alone (OR 0.668, 95% CrI 0.459-0.931) were associated with a significantly lower likelihood of 12-month recurrence rate. In the sensitivity analysis, out of eight different interventions compared to WLC alone, PDD by 5-aminolevulinic acid plus SIIC (OR 0.327, 95% CrI 0.159-0.646) and by hexaminolevulinic acid plus SIIC (OR 0.376, 95% CrI 0.172-0.783) were both associated with a significantly lower likelihood of 12-month recurrence rate. NBI with and without SIIC was not associated with a significantly lower likelihood of 12-month recurrence rate (OR 0.385, 95% CrI 0.105-1.29 and OR 0.653, 95% CrI 0.343-1.15).
CONCLUSION
Blue-light cystoscopy during TURBT with concomitant SIIC seems to yield superior recurrence outcomes in patients with non-muscle-invasive bladder cancer. The use of PDD was able to reduce the 12-month recurrence rate; moreover, concomitant SIIC increased this risk benefit by a 32% additional reduction in odds ratio. Although using PDD could reduce the recurrence rate, SIIC remains necessary. Moreover, ranking analysis showed that both PDD and NBI, plus SIIC, were better than these techniques alone.
Topics: Administration, Intravesical; Combined Modality Therapy; Cystectomy; Humans; Neoplasm Recurrence, Local; Network Meta-Analysis; Randomized Controlled Trials as Topic; Urethra; Urinary Bladder Neoplasms
PubMed: 33683778
DOI: 10.1111/bju.15383 -
The Cochrane Database of Systematic... Jan 2021Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in...
BACKGROUND
Multiple studies have identified the prognostic relevance of extent of resection in the management of glioma. Different intraoperative technologies have emerged in recent years with unknown comparative efficacy in optimising extent of resection. One previous Cochrane Review provided low- to very low-certainty evidence in single trial analyses and synthesis of results was not possible. The role of intraoperative technology in maximising extent of resection remains uncertain. Due to the multiple complementary technologies available, this research question is amenable to a network meta-analysis methodological approach.
OBJECTIVES
To establish the comparative effectiveness and risk profile of specific intraoperative imaging technologies using a network meta-analysis and to identify cost analyses and economic evaluations as part of a brief economic commentary.
SEARCH METHODS
We searched CENTRAL (2020, Issue 5), MEDLINE via Ovid to May week 2 2020, and Embase via Ovid to 2020 week 20. We performed backward searching of all identified studies. We handsearched two journals, Neuro-oncology and the Journal of Neuro-oncology from 1990 to 2019 including all conference abstracts. Finally, we contacted recognised experts in neuro-oncology to identify any additional eligible studies and acquire information on ongoing randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs evaluating people of all ages with presumed new or recurrent glial tumours (of any location or histology) from clinical examination and imaging (computed tomography (CT) or magnetic resonance imaging (MRI), or both). Additional imaging modalities (e.g. positron emission tomography, magnetic resonance spectroscopy) were not mandatory. Interventions included fluorescence-guided surgery, intraoperative ultrasound, neuronavigation (with or without additional image processing, e.g. tractography), and intraoperative MRI.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the search results for relevance, undertook critical appraisal according to known guidelines, and extracted data using a prespecified pro forma.
MAIN RESULTS
We identified four RCTs, using different intraoperative imaging technologies: intraoperative magnetic resonance imaging (iMRI) (2 trials, with 58 and 14 participants); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around winter 2020. We identified no published trials for intraoperative ultrasound. Network meta-analyses or traditional meta-analyses were not appropriate due to absence of homogeneous trials across imaging technologies. Of the included trials, there was notable heterogeneity in tumour location and imaging technologies utilised in control arms. There were significant concerns regarding risk of bias in all the included studies. One trial of iMRI found increased extent of resection (risk ratio (RR) for incomplete resection was 0.13, 95% confidence interval (CI) 0.02 to 0.96; 49 participants; very low-certainty evidence) and one trial of 5-ALA (RR for incomplete resection was 0.55, 95% CI 0.42 to 0.71; 270 participants; low-certainty evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants; therefore, the trial provided very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-certainty evidence). Overall, the proportion of reported events was low in most trials and, therefore, issues with power to detect differences in outcomes that may or may not have been present. Survival outcomes were not adequately reported, although one trial reported no evidence of improvement in overall survival with 5-ALA (hazard ratio (HR) 0.82, 95% CI 0.62 to 1.07; 270 participants; low-certainty evidence). Data for quality of life were only available for one study and there was significant attrition bias (very low-certainty evidence).
AUTHORS' CONCLUSIONS
Intraoperative imaging technologies, specifically 5-ALA and iMRI, may be of benefit in maximising extent of resection in participants with high-grade glioma. However, this is based on low- to very low-certainty evidence. Therefore, the short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. Network and traditional meta-analyses were not possible due to the identified high risk of bias, heterogeneity, and small trials included in this review. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, one non-systematic review of economic studies suggested that, compared with standard surgery, use of image-guided surgery has an uncertain effect on costs and that 5-ALA was more costly. Further research, including completion of ongoing trials of ultrasound-guided surgery, is needed.
Topics: Aminolevulinic Acid; Bias; Brain Neoplasms; Glioma; Humans; Intraoperative Care; Magnetic Resonance Imaging, Interventional; Network Meta-Analysis; Neuronavigation; Optical Imaging; Randomized Controlled Trials as Topic
PubMed: 33428222
DOI: 10.1002/14651858.CD013630.pub2 -
Diagnostics (Basel, Switzerland) Dec 2020: A very important aspect in the treatment of high-grade glioma is gross total resection to reduce the risk of tumor recurrence. One of the methods to facilitate this... (Review)
Review
: A very important aspect in the treatment of high-grade glioma is gross total resection to reduce the risk of tumor recurrence. One of the methods to facilitate this task is intraoperative fluorescence navigation. The aim of the study was to compare the dyes used in this technique fluorescent intraoperative navigation in terms of the mechanism of action and influence on the treatment of patients. : The review was carried out on the basis of articles found in PubMed, Google Scholar, and BMC search engines, as well as those identified by searched bibliographies and suggested by experts during the preparation of the article. The database analysis was performed for the following phrases: "glioma", "glioblastoma", "ALA", "5ALA", "5-ALA", "aminolevulinic acid", "levulinic acid", "fluorescein", "ICG", "indocyanine green", and "fluorescence navigation". : After analyzing 913 citations identified on the basis of the search criteria, we included 36 studies in the review. On the basis of the analyzed articles, we found that 5-aminolevulinic acid and fluorescein are highly effective in improving the percentage of gross total resection achieved in high-grade glioma surgery. At the same time, the limitations resulting from the use of these methods are marked-higher costs of the procedure and the need to have neurosurgical microscope in combination with a special light filter in the case of 5-aminolevulinic acid (5-ALA), and low specificity for neoplastic cells and the dependence on the degree of damage to the blood-brain barrier in the intensity of fluorescence in the case of fluorescein. The use of indocyanine green in the visualization of glioma cells is relatively unknown, but some researchers have suggested its utility and the benefits of using it simultaneously with other dyes. : The use of intraoperative fluorescence navigation with the use of 5-aminolevulinic acid and fluorescein allows the range of high-grade glioma resection to be increased.
PubMed: 33339439
DOI: 10.3390/diagnostics10121100