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Photodiagnosis and Photodynamic Therapy Jun 2024Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates...
A Nomogram to Predict Anal Condyloma Acuminatum Recurrence in HIV-negative Patients Following Photodynamic Therapy: A Decade-Long Retrospective Clinical Study at a Single Tertiary Hospital.
BACKGROUND
Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT.
METHODS
A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling.
RESULTS
Among the 176 patients included, 33 (18.75%) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95% CI: 0.818-0.935) and a significant net benefit in decision curve analysis.
CONCLUSIONS
The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.
PubMed: 38871015
DOI: 10.1016/j.pdpdt.2024.104245 -
Photodiagnosis and Photodynamic Therapy Jun 2024This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). (Review)
Review
BACKGROUND
This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC).
METHODS
Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature.
RESULTS
The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin®, Foscan® and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin® and Foscan® were the most used photosensitisers, counting more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue.
CONCLUSIONS
Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations considering four photosensitisers, Photofrin® was the most used but more recent photosensitisers like Foscan have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
PubMed: 38857775
DOI: 10.1016/j.pdpdt.2024.104242 -
F1000Research 2024Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic...
BACKGROUND
Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions.
CASE PRESENTATION
The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT.
RESULTS
A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications.
CONCLUSION
The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.
Topics: Humans; Male; Adult; Photochemotherapy; Lichen Planus, Oral; Mouth Mucosa; Low-Level Light Therapy; Combined Modality Therapy; Aminolevulinic Acid
PubMed: 38854440
DOI: 10.12688/f1000research.146733.1 -
Life Sciences Jun 2024As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its... (Review)
Review
As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT.
PubMed: 38852796
DOI: 10.1016/j.lfs.2024.122808 -
Photodiagnosis and Photodynamic Therapy Jun 2024Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated...
BACKGROUND
Acne vulgaris is a species-specific human disease. To date, there has been no established human sebocyte cell line of Asian origin. Our previous study has demonstrated the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of acne vulgaris, primarily attributed to its cytotoxic properties; however, its regulatory mechanism remains largely unknown.
OBJECTIVES
To establish an immortalized human sebocyte cell line derived from the Chinese population and investigate the underlying mechanism of ALA-PDT.
METHODS
Human primary sebocytes were transfected with the human tert gene (h-tert). The biological characteristics, including cell proliferation, cell markers, and sebum secretion function, were compared between primary sebocytes and the immortalized sebocytes (XL-i-20). Stimulations such as ALA-PDT, were applied respectively to both primary sebocytes and XL-i-20 cells to assess changes in their cellular functions. The transcriptome differences between primary sebocytes and XL-i-20 sebocytes were investigated using RNA-seq analysis. The XL-i-20 cell line was used to establish a sebaceous gland (SG) organoid culture, serving as a representative model of SG for the investigation of ALA-PDT.
RESULTS
The h-tert immortalized sebocyte cell line exhibited the ability to be consecutively cultured for more than fifty passages. Both primary and immortalized cells expressed sebaceous marker, epithelial membrane antigens (EMA, or MUC-1), Cytokeratin 7 (CK7) and adipose differentiation-related protein associated antigens (ADRP), and maintained sebum secretion function. The proliferative capacity of XL-i-20 was found to be significantly higher than that of primary sebocytes. The responses of XL-i-20 to ALA-PDT were indistinguishable from those elicited by primary sebocytes. Cell viability and sebum secretion were decreased after ALA-PDT in both two cell lines, and lipid-related proteins (SREBP-1/PPARγ) were down-regulated. The transcriptome data consistently demonstrated upregulation of genes related to inflammatory response and downregulation of genes involved in lipid metabolism in both cell types following PDT. The analysis of common differential genes of primary sebocytes and XL-i-20 sebocytes post ALA-PDT showed that TNF signaling pathways, MAPK signaling pathways and JAK-STAT signaling pathways were activated. The SG organoids were spherical, which expressed markers of FANS and PLET1. Ki-67 was down-regulated after ALA-PDT.
CONCLUSIONS
We have developed an h-tert immortalized sebocyte cell line from an Asian firstly, which maintains the essential characteristics of its parent primary sebocytes. Moreover, XL-i-20 sebocyte exhibited a significant respond to ALA-PDT, demonstrating comparable phenotypic and molecular changes to primary sebocytes. Therefore, XL-i-20 and its derived SG organoid serve as appropriate in vitro models for investigating the efficacy and mechanisms of ALA-PDT in SG-related diseases.
PubMed: 38848883
DOI: 10.1016/j.pdpdt.2024.104238 -
Clinical, Cosmetic and Investigational... 2024ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical...
OBJECTIVE
ALA-PDT (5-aminolevulinic acid photodynamic therapy) is a central modality in the treatment of skin diseases. Increasing the bioavailability of ALA remains a critical issue. With this in mind, our study explores a novel route of ALA delivery by loading acrylic nanoparticles (ANPs).
METHODS
ALA-ANPs were synthesized by emulsion polymerisation and characterised by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effects of ALA-ANPs on HaCaT cell line were evaluated, including characteristics, morphological changes, protoporphyrin IX (PpIX) fluorescence kinetics, reactive oxygen species (ROS) levels, mitochondrial membrane potential and ki67 expression in these cells.
RESULTS
The ANPs had uniform sizes, smooth surfaces and excellent light transmittance, with diameters of 150-200 nm. In contrast, the ALA - ANPs had uneven surfaces and poor light transmittance, with diameters of 220-250 nm. During 12 hours of co-incubation of HaCaT cells with ALA, the intracellular accumulation of PpIX increased over time. Notably, after 6 hours of incubation, PpIX levels induced by 1.81 mg/mL ALA-ANPs exceeded those induced by 1.0 mM ALA (). CCK-8 results showed a positive correlation between PDT-induced inhibition of HaCaT cell proliferation and ALA concentration when ALA concentration remained below 2.0 mM. Compared to the 1.0 mM ALA group, the 1.81 mg/mL ALA-ANPs group showed decreased mitochondrial membrane potential, ki67 immunofluorescence intensity and cell proliferation. In contrast, ROS levels were significantly increased in the 1.81 mg/mL ALA-ANPs group (p < 0.01).
CONCLUSION
Loading ANPs provide improved stability and potency for ALA. The ALA-ANPs-PDT approach has superior inhibitory effects on HaCaT proliferation in vitro.
PubMed: 38835518
DOI: 10.2147/CCID.S458525 -
Frontiers in Immunology 2024
Topics: Humans; Cellular Microenvironment; Animals; Skin Diseases; Epithelial Cells; Skin
PubMed: 38831926
DOI: 10.3389/fimmu.2024.1428209 -
PloS One 2024Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy...
OBJECTIVES
Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy volunteers.
DESIGN
Prospective cohort study.
SETTING
Measurements were performed in Leiden University Medical Center, the Netherlands.
PARTICIPANTS
Healthy volunteers enrolled from July to September 2020.
INTERVENTIONS
Two ALA plasters were placed parasternal left and right, with a 3-hour time interval, to examine the influence of the calendar time on the value of mitoPO2. We measured mitoPO2 at 4, 5, 7, 10, 28, and 31 hours after ALA plaster 1 application, and at 4, 5, 7, 25, and 28 hours after ALA plaster 2 application.
PRIMARY AND SECONDARY OUTCOME MEASURES
At each time point, five mitoPO2 measurements were performed. Within-subject variability was defined as the standard deviation (SD) of the mean of five measurements per timepoint of a study participant. The between-subject variability was the SD of the mean mitoPO2 value of the study population per timepoint.
RESULTS
In 16 completed inclusions, median mitoPO2 values and within-subject variability were relatively similar over time at all time points for both plasters. An increase in overall between-subject variability was seen after 25 hours ALA plaster time (19.6 mm Hg vs 23.9 mm Hg after respectively 10 and 25 hours ALA plaster time).
CONCLUSIONS
The mitoPO2 values and within-subject variability remained relatively stable over time in healthy volunteers. An increase in between-subject variability was seen after 25 hours ALA plaster time warranting replacement of the ALA plaster one day after its application.
TRIAL REGISTRATION
ClinicalTrials.gov with trial number NCT04626661.
Topics: Humans; Male; Female; Healthy Volunteers; Adult; Oxygen; Prospective Studies; Mitochondria; Middle Aged; Aminolevulinic Acid; Oxygen Consumption; Young Adult; Netherlands
PubMed: 38829894
DOI: 10.1371/journal.pone.0300602 -
BMC Biomedical Engineering Jun 2024Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical...
BACKGROUND
Visualization of cancer during breast conserving surgery (BCS) remains challenging; the BCS reoperation rate is reported to be 20-70% of patients. An urgent clinical need exists for real-time intraoperative visualization of breast carcinomas during BCS. We previously demonstrated the ability of a prototype imaging device to identify breast carcinoma in excised surgical specimens following 5-aminolevulinic acid (5-ALA) administration. However, this prototype device was not designed to image the surgical cavity for remaining carcinoma after the excised lumpectomy specimen is removed. A new handheld fluorescence (FL) imaging prototype device, designed to image both excised specimens and within the surgical cavity, was assessed in a clinical trial to evaluate its clinical utility for first-in-human, real-time intraoperative imaging during index BCS.
RESULTS
The imaging device combines consumer-grade imaging sensory technology with miniature light-emitting diodes (LEDs) and multiband optical filtering to capture high-resolution white light (WL) and FL digital images and videos. The technology allows for visualization of protoporphyrin IX (PpIX), which fluoresces red when excited by violet-blue light. To date, patients have received bodyweight (BW) 5-ALA orally 2-4 h before imaging to facilitate the accumulation of PpIX within tumour cells. Tissue types were identified based on their colour appearance. Breast tumours in sectioned lumpectomies appeared red, which contrasted against the green connective tissues and orange-brown adipose tissues. In addition, ductal carcinoma in situ (DCIS) that was missed during intraoperative standard of care was identified at the surgical margin at <1 mm depth. In addition, artifacts due to the surgical drape, illumination, and blood within the surgical cavity were discovered.
CONCLUSIONS
This study has demonstrated the detection of a grossly occult positive margin intraoperatively. Artifacts from imaging within the surgical cavity have been identified, and potential mitigations have been proposed.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01837225 (Trial start date is September 2010. It was registered to ClinicalTrials.gov retrospectively on April 23, 2013, then later updated on April 9, 2020, to reflect the introduction of the new imaging device.).
PubMed: 38822389
DOI: 10.1186/s42490-024-00079-9 -
Photodiagnosis and Photodynamic Therapy May 2024Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to...
Effectiveness of 5-aminolevulinic acid photodynamic therapy in treating dissecting cellulitis of the scalp and pathological changes in skin lesions: A retrospective study.
BACKGROUND
Dissecting cellulitis of the scalp (DCS) has a significant impact on the physical well-being and body image of the patient. Since DCS often responds poorly to conventional treatments, there is a need to identify alternative treatment strategies. This study aimed to explore the effectiveness of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating DCS.
METHODS
Twelve male patients with DCS treated solely with ALA-PDT between June 2022 and June 2023 at our institution were enrolled in this study. Two patients underwent a biopsy before and after treatment for comparison. The efficacy of the treatments was assessed 10 days after treatment by evaluating the symptom scores recorded on medical records and by assessing the photographs acquired before and after treatment. In addition, the impact of the treatment on pain relief and median recurrence rate were also extracted.
RESULTS
Out of the 12 enrolled patients, the majority of the patients (75%) had a significant reduction in the nodules or abscesses. The pain relief was significant in 3 patients (25%), and moderate in 7 patients (58.3%). For the subcutaneous sinus tract symptoms, 3 patients (27.3%) showed moderate improvement, and 7 (63.6%) had a mild improvement. Six patients (75%) had mild improvement in their alopecia. The pathology results showed a decrease in the number of lymphocytes, macrophages, and neutrophils within the skin lesions following the administration of ALA-PDT.
CONCLUSION
ALA-PDT can effectively reduce the DCS symptoms and the number of lymphocytes, macrophages, and neutrophils within the skin lesions.
PubMed: 38821237
DOI: 10.1016/j.pdpdt.2024.104227