OBJECTIVE: To explore whether microneedle pretreatment can significantly improve the efficacy and safety of 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) in the treatment of oral leukoplakia. METHODS: A non-randomized controlled clinical trial was conducted. Patients with clinical and pathological diagnosis of oral leukoplakia in the Department of Oral Mucosa, Peking University School and Hospital of Stomatology were divided into experimental group and control group. The control group was treated with conventional ALA-PDT, and the experimental group was pretreated with micro- needle buckling under superficial anesthesia with lidocaine before conventional ALA-PDT. The clinical manifestations of the two groups were recorded, the lesion area was measured, the clinical efficacy was evaluated, the number of treatment sessions and treatment unit duration were analyzed, and the pain after treatment was evaluated by visual analogue scale. The above data of the two groups were statistically analyzed. RESULTS: A total of 11 patients were included in the experimental group and 19 patients were included in the control group. The complete remission rate of the experimental group and the control group was 45.5% and 36.8%, the partial remission rate was 54.5% and 57.9%, and the no remission rate was 0% and 5%, respectively. There was no significant difference in the treatment effect between the two groups. Meanwhile, the treatment unit duration of the experimental group and the control group were (9.05±5.74) min/cm² and (21.38±15.44) min/cm², respectively, and the number of treatment sessions were (2.36±0.67) times and (3.58±1.57) times, respectively. These differences between the two groups were statistically significant (t=-3.125, P < 0.05; t=-2.932, P < 0.05). Similarly, multiple linear regression analysis with 7 factors including age, dysplastic pathology, lesion classification, etc., also confirmed that pretreatment could significantly shorten the treatment unit duration (P < 0.05). In addition, there was no significant difference in pain score (visual analogue scale) between the two groups after treatment, and the microneedle puncture pretreatment did not increase the adverse reactions of ALA-PDT treatment. CONCLUSION Microneedle pretreatment followed by conventional ALA-PDT shows a good clinical effect on oral leukoplakia, which can significantly shorten the clinical treatment time, reduce the number of visits, and save medical costs.
Humans ; Photochemotherapy/instrumentation* ; Leukoplakia, Oral/drug therapy* ; Aminolevulinic Acid/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; Needles ; Photosensitizing Agents/therapeutic use* ; Aged ; Combined Modality Therapy

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as certain forms of non-melanoma skin cancer (NMSC) or keratinocyte carcinoma, are the most common forms of malignant neoplasms worldwide (Sharp et al., 2024). BCC and cSCC have been identified as two major components of NMSC, comprising one-third of all malignancies (Burton et al., 2016). Generally speaking, patients with NMSC tend to have relatively favorable survival outcomes, while different histopathological subtypes of NMSC exhibit distinct biological behaviors (Stătescu et al., 2023). Keratinocyte carcinoma, although not considered as deadly as melanoma, tends to metastasize if left untreated (Civantos et al., 2023; Nanz et al., 2024). cSCC can evolve locally, then aggressively metastasize, invade, and even lead to fatal consequences in a subset of patients (Winge et al., 2023). A solid, pigmented, smooth plaque or a hyperkeratotic papule with or without central ulceration and hemorrhage appears to be characteristic of cSCC (Thompson et al., 2016; Zhou et al., 2023). Of note, a rare type of intraepidermal cSCC in situ often appears as a velvety, demarcated, slightly raised erythematous plaque on the genitalia of men (Yamaguchi et al., 2016). Accounting for approximately 16.0% of scalp tumors and with a rising incidence, cSCC is now the second most common NMSC in humans (Verdaguer-Faja et al., 2024). According to the latest statistics, up to 2%‒5% of cSCCs in situ may gradually progress into invasive cSCCs in the final step (Rentroia-Pacheco et al., 2023). Several risk factors for the carcinogenesis and development of cSCC have been identified, including age, accumulative exposure to ultraviolet light radiation A and B, human papillomavirus infection, arsenic ingestion, chronic scarring, xeroderma pigmentosa, a relevant history of ionizing radiation, androgenetic alopecia in males, and immunosuppression therapy (Martinez and Otley, 2001; Welsch et al., 2012; Mortaja and Demehri, 2023).
Humans ; Aminolevulinic Acid/therapeutic use* ; Skin Neoplasms/pathology* ; Photochemotherapy/methods* ; Female ; Carcinoma, Squamous Cell/pathology* ; Middle Aged ; Photosensitizing Agents/therapeutic use* ; Carcinoma, Basal Cell/drug therapy*

With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature. Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
Aminolevulinic Acid ; administration & dosage ; therapeutic use ; Humans ; Leukoplakia, Oral ; therapy ; Photochemotherapy ; methods ; Photosensitizing Agents ; administration & dosage ; therapeutic use ; Practice Guidelines as Topic

OBJECTIVETo evaluate the photodynamic therapy (PDT) against multi-antibiotic-resistant Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S.epidermidis) obtained from patients with chronic rhinosinusitis (CRS).

METHODSForty-five CRS patients who had been given medical treatment but still needed endoscopic surgery were included in this study. The mucus from middle meatus was collected from these patients during surgery, followed by separation of S. aureus and S. epidermidis and drug sensitive test. The strains which could form biofilm were selected. Light emitting diode (LED) array with a major wavelength of (633±10) nm was used as light source and 5-Aminolevulinic acid (ALA) was used as photosensitizer in this PDT experiment. The safe range of LED dose and ALA concentration which were not toxic to bacteria by themselves were confirmed, and then did PDT experiment on S. aureus and S. epidermidis. The data of bacterial colony forming unit were transformed to lgCFU before statistical analysis.The Graph Pad Prism 5 software was used to analyzed the data.

RESULTSThirteen S. aureus and 16 S. epidermidis were included in this experiment(from 45 patients), all of them were multi-antibiotic-resistant bacteria, and four of S. aureus and five of S. epidermidis could form biofilm in each group. In planktonic S. aureus experiment, the mean lgCFU was 8.32±0.31 in control group whereas the experiment group was 6.47±0.67 (t=9.01, P<0.01), and in planktonic S. epidermidis experiment the final data was 8.34±0.20 (control group) and 6.97±0.59 (experiment group) (t=8.84, P<0.01). In biofilm S. aureus experiment, the mean lgCFU was 8.68±0.05 (control group), 6.90±0.96(experiment group) (t=3.68, P<0.05); and in biofilm S. epidermidis experiment the data was 8.67±0.05 (control group), 7.29±0.61 (experiment group, t=5.07, P<0.01).

CONCLUSIONOur results demonstrated that ALA-mediated PDT on multi-antibiotic-resistant S. aureus and S. epidermidis from CRS patients was effective in vitro. Additional work defining if the PDT treatment would damage the nasal mucosa and further checking the effectiveness of PDT in vivo is still needed.

Aminolevulinic Acid ; therapeutic use ; Anti-Bacterial Agents ; Biofilms ; Drug Resistance, Multiple, Bacterial ; Humans ; Light ; Photochemotherapy ; Photosensitizing Agents ; therapeutic use ; Rhinitis ; drug therapy ; microbiology ; Sinusitis ; drug therapy ; microbiology ; Staphylococcal Infections ; complications ; drug therapy ; Staphylococcus

Although 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) has been demonstrated to be a novel and effective therapeutic modality for some human malignancies, its effect and mechanism on glioma are still controversial. Previous studies have reported that 5-ALA-PDT induced necrosis of C6 rat glioma cells in vitro. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on C6 gliomas implanted in rats in vivo. Twenty-four rats bearing similar size of subcutaneously implanted C6 rat glioma were randomly divided into 3 groups: receiving 5-ALA-PDT (group A), laser irradiation (group B), and mock procedures but without any treatment (group C), respectively. The growth, histology, microvessel density (MVD), and apoptosis of the grafts in each group were determined after the treatments. As compared with groups B and C, the volume of tumor grafts was significantly reduced (P<0.05), MVD was significantly decreased (P<0.001), and the cellular necrosis was obviously increased in group A. There was no significant difference in apoptosis among the three groups. The in vivo studies confirmed that 5-ALA-PDT may be an effective treatment for gliomas by inhibiting the tumor growth. The mechanism underlying may involve increasing the cellular necrosis but not inducing the cellular apoptosis, which may result from the destruction of the tumor microvessels.
Aminolevulinic Acid ; pharmacology ; therapeutic use ; Animals ; Brain Neoplasms ; blood supply ; drug therapy ; pathology ; Cell Line, Tumor ; Glioma ; blood supply ; drug therapy ; pathology ; Microvessels ; drug effects ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Xenograft Model Antitumor Assays

BACKGROUNDPhotodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an emerging technique for the treatment of genital human papillomavirus (HPV)-induced benign and premalignant lesions. We report here in a case series of condyloma acuminata (CA) in pregnancy successfully treated with ALA-PDT.

METHODSFive pregnant patients with CA received three to four times treatment respectively. Patients were followed up for 6 - 23 months after treatment.

RESULTSThe clearance rate of genital warts was 100%. No recurrence was found during the follow-up period. Major adverse events reported were mild erosion, pain, and local edema. All pregnancies resulted in healthy live births without delivery complications.

CONCLUSIONSPDT with topical ALA seems to be safe and effective in the treatment of CA in pregnancy. It demonstrated high clearance rate of warts, was well-tolerated by patients, and showed no adverse effects on mothers or fetuses. ALA-PDT may be an ideal strategy of treatment for pregnant women with CA.

Adult ; Aminolevulinic Acid ; therapeutic use ; Condylomata Acuminata ; drug therapy ; Female ; Humans ; Photochemotherapy ; methods ; Pregnancy

OBJECTIVETo investigate the efficacy, adverse reaction and prognosis of liquid nitrogen freezing combined with 5-aminolaevulinic acid-photodynamic therapy (ALA-PDT) in the treatment of condyloma acuminatum in men.

METHODSWe collected medical histories and conducted physical examinations for 35 male patients with condyloma acuminatum in the outpatient department, and treated them by liquid nitrogen freezing combined with ALA-PDT every 7-10 days. We recorded the skin lesions and adverse events each time and followed up the patients at 4 and 24 weeks after treatment.

RESULTSThe 35 patients were aged 17-71 (median 31) years, and their average course of disease was 30-180 (mean 60) days. The skin lesion area was reduced remarkably after 3 times of liquid nitrogen freezing combined with ALA-PDT, 16-140 (median 38) mm2 for the first time, 6-63 (median 13) mm2 for the second, and 0-10 (median 3) mm2 for the third, with statistically significant differences (P < 0.01). Two cases (5.7%) relapsed at 4 weeks and 4 cases (11.4% ) at 24 weeks.

CONCLUSIONLiquid nitrogen freezing combined with ALA-PDT is better than either liquid nitrogen freezing or ALA-PDT alone for the treatment of condyloma acuminatum in men.

Adolescent ; Adult ; Aged ; Aminolevulinic Acid ; administration & dosage ; therapeutic use ; Condylomata Acuminata ; therapy ; Cryotherapy ; Humans ; Male ; Middle Aged ; Photochemotherapy ; Prognosis ; Young Adult

OBJECTIVETo observe the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for treating psoriasis vulgaris in guinea pigs.

METHODSExperimental psoriasis vulgaris was induced in guinea pigs by application of 5% propranolol on the ear skin. After dressing of the skin lesion with 20% ALA solution for 4 h, the lesions were irradiated with a semiconductor laser at the wavelength of 635 nm and energy density of 12 J/cm(2). The guinea pigs were divided into control group, ALA only group, light only group, single ALA-PDT treatment group and twice ALA-PDT treatment group. In each group, gross observation and biopsy of the skin lesions was conducted on days 7, 14, 21 and 28 after the treatment.

RESULTSIn terms of gross observation of the lesion, epidermal thickness and proliferating cell nuclear antigen (PCNA) expression, ALA-PDT treatment showed obvious therapeutic effect on the skin lesion, and two treatment sessions resulted in better effect than a single session.

CONCLUSIONALA-PDT can cure psoriasis vulgaris lesions characterized by abnormal epidermal proliferation in guinea pigs, and multiple treatment sessions can achieve better effects.

Acne Vulgaris ; drug therapy ; Aminolevulinic Acid ; therapeutic use ; Animals ; Guinea Pigs ; Photochemotherapy ; Photosensitizing Agents ; therapeutic use ; Psoriasis ; drug therapy

OBJECTIVETo investigate the efficacy and safety of photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) on cervical condylomata acuminata.

METHODSPatients with cervical condylomata (n=30) were allocated into primary and recurrent group, and were given topical ALA under occlusive dressing for 3 hours followed by irradiation with semiconductor laser at a dose of 100 Jcm(-2) and a power of 100 mW. The treatment was repeated 7 days later if the lesion was not completely removed after the first treatment. Complete response rate and recurrence rate of wart lesions as well as rate of adverse reaction were analyzed.

RESULTSThe total complete response rate of PDT was 100% and the total recurrence rate was 5% after 3 months of follow-up. Recurrence rate of recurrent group was significantly lower than that of prior managements (100%, P<0.01). The side effects of PDT in patients mainly included mild burning and/or stinging restricted to the illuminated areas, and was significant lower than their own control (25% vs. 100%, P<0.05).

CONCLUSIONCompared with conventional therapies, topical application of ALA-PDT is a simple, effective, safe, well-tolerated, and low recurrence rate treatment for cervical condylomata acuminata.

Adult ; Aminolevulinic Acid ; therapeutic use ; Condylomata Acuminata ; drug therapy ; Female ; Humans ; Middle Aged ; Photochemotherapy ; adverse effects ; Photosensitizing Agents ; therapeutic use ; Recurrence ; Uterine Cervical Diseases ; drug therapy ; Young Adult

OBJECTIVETo investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoricidal mechanism.

METHODSCultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9 MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay.

RESULTSThe tumor model was successfully developed. The tumor in the nude mice emitted the red fluorescence under the Leica LT-9 MACIMSYSPULS. The tumor volumes were (0.189+/-0.010) cm(3), (0.183+/-0.011) cm(3), (0.185+/-0.019)cm(3), (0.182+/-0.015)cm(3) for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294+/-0.010) cm(3), (0.280+/-0.013) cm(3), (0.278+/-0.016) cm(3), (0.183+/-0.014) cm(3); at day 7, (0.409+/-0.016) cm(3), (0.411+/-0.009) cm(3), (0.407+/-0.015) cm(3), (0.221+/-0.008) cm(3); at day 14, (0.970+/-0.055) cm(3), (0.976+/-0.054) cm(3), (0.981+/-0.032)cm(3), (0.318+/-0.005) cm(3); at day 21, (1.495+/-0.059) cm(3), (1.513+/-0.057) cm(3), (1.524+/-0.063) cm(3), (0.446+/-0.042) cm(3) (F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups.

CONCLUSIONS5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic acid-mediated photodynamic therapy (ALA- PDT) appears to be a promising therapy for human gastric cancer, whose mechanism involves in the destruction of the tumors partly by apoptosis other than necrosis.

Aminolevulinic Acid ; therapeutic use ; Animals ; Cell Line, Tumor ; Female ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neoplasms, Experimental ; Photochemotherapy ; Stomach Neoplasms ; therapy ; Xenograft Model Antitumor Assays