Peripheral blood CD4+ T cell count predicts recurrence of condyloma acuminatum after photodynamic therapy in HIV-positive patients.

BACKGROUND: Few studies have reported postoperative relapse of condyloma acuminatum (CA) after 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in human immunodeficiency virus (HIV) positive patients. METHODS: The clinical data of HIV-positive CA patients treated with ALA-PDT from October 2018 to December 2019 were analyzed retrospectively. Univariate and multivariate Cox regression was used to analyze the variables related to postoperative recurrence. Pearson correlation test was employed to analyze the correlation between CD4+ T cell count and postoperative recurrence rate. Kaplan-Meier method was used to compare the CA recurrence after ALA-PDT in low CD4 group and high CD4 group. RESULTS: A total of 38 HIV-positive patients with CA were included in the study. Among them, 26 patients experienced CA recurrence within 6 months, and the recurrence rate was 68.4%. CD4+ T cell count was 187.0 (79.0-596.0) cells/µl in relapsed patients and 406.0 (89.0-612.0) cells/µl in non-relapsed patients, showing a statistically significant difference (p = .005). Pearson correlation coefficient analysis revealed a negative correlation between CD4+ T cell count and postoperative recurrence rate (p = .005, r = -.443). Univariate regression analysis showed that CD4+ T cell count was correlated with postoperative recurrence, hazard ratio (HR) was 0.99 [95% Confidence interval (CI) = 0.99-1.0, p = .012]. Multivariate Cox regression analysis showed that with the low CD4+ T cell count as the reference, the high CD4+ T cell count was negatively correlated with postoperative recurrence (HR = 0.09, 95% CI 0.01-0.87, p = .038). CONCLUSIONS: Peripheral blood CD4+ T cell count can predict the CA recurrence rate after ALA-PDT in HIV-positive patients.

Rational of topical photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) for treatment of endocervical canal low-grade squamous intraepithelial lesion with high-risk human papillomavirus infection.

BACKGROUND: The detection and continuous monitoring of low-grade squamous intraepithelial lesions (LSIL) within the endocervical canal pose considerable challenges, and the effectiveness of ablation treatment is also constrained. In this context, the potential efficacy of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) in targeting these concealed lesions merits exploration. The present study undertakes a comprehensive analysis of the clinical effectiveness and safety aspects associated with the utilization of 5-ALA PDT. METHODS: A retrospective analysis was conducted on a cohort of 13 patients who were diagnosed with LSIL within the endocervical canal, concomitant with high-risk human papillomavirus (hrHPV) infection. These patients were subjected to treatment with 5-ALA PDT and subsequently monitored over a period of 3-6 months following the intervention. RESULTS: The study cohort comprised 13 patients, among whom 4 presented with isolated lesions within the endocervical canal, 5 exhibited LSIL involving both the endocervical canal and the cervix vaginal portion, 3 displayed LSIL within the endocervical canal in conjunction with vaginal involvement, and 1 patient demonstrated lesions across all three of these anatomical sites. All identified lesions underwent therapeutic intervention via 5-ALA PDT. Before treatment initiation, 9 patients returned positive results in the liquid-based cytologic test (LBC), 4 displayed concurrent multiple hrHPV infections, and 5 manifested infections specifically with HPV 16/18. Subsequent to the application of 5-ALA PDT, regression was observed in the LBC results of all patients, with only 3 individuals retaining a singular type of hrHPV infection. Adverse reactions following treatment encompassed mild aberrant vaginal secretions and mild to moderately pronounced distending abdominal discomfort, all of which were remitted within a span of 7 days. CONCLUSIONS: Within the context of LSIL within the endocervical canal in association with hrHPV infection, the findings affirm the efficacy and safety of 5-ALA PDT as a viable therapeutic modality.

Modified 5-aminolevulinic acid photodynamic therapy reduces pain and improves therapeutic effects in cutaneous squamous cell carcinoma mouse model.

BACKGROUND AND OBJECTIVES: Conventional ALA-PDT (C-PDT) has limited efficacy in cutaneous squamous cell carcinoma (cSCC), and there is obvious pain during treatment, which limits its clinical application. We sought to modify photodynamic therapy into a more painless and effective treatment. METHODS: We modified C-PDT by reducing the incubation time of the pro-sensitizer and increasing the light dose; we named this method modified ALA-PDT (M-PDT). We compared the pain response and curative effect between C-PDT and M-PDT in cSCC mouse models. Pain-related proteins were examined by western blot analysis and immunohistochemistry. Tumor progression-associated signaling pathways were analyzed by RNA-seq and western blot analysis. Reactive oxygen species (ROS) generation was measured with a ROS test kit and Microplate reader. RESULTS: M-PDT greatly reduced pain during treatment. Interestingly, when the cSCC tumor volume increased to 150-200 mm3 , M-PDT almost completely eliminated the tumors, while C-PDT did not. The better curative effect of M-PDT might be due to the stronger suppression of the Stat3, Erk1/2, and mTOR signaling pathways. Moreover, flow cytometry demonstrated that M-PDT could recruit CD8+ T cells to inhibit cSCC progression. Further investigation determined that the different mechanisms of C-PDT and M-PDT were related to more ROS generation induced by M-PDT. CONCLUSIONS: Our results suggest that M-PDT, which is more painless and effective than C-PDT, is expected to provide a solution for the treatment of cSCC.

Management of patients with positive margin after conization for high-grade cervical intraepithelial lesions.

BACKGROUND AND OBJECTIVE: To evaluate the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in the treatment of patients with positive margin in comparison to regular follow-up, and a repeat cervical conization. MATERIALS AND METHODS: A retrospective analysis was conducted using 83 patients with pathologically confirmed high-grade cervical intraepithelial neoplasia (CIN) with a positive margin after conization. The management methods and patient prognosis were analyzed and compared. RESULTS: Thirty-five, 33, and 15 patients were treated for regular follow-up, ALA-PDT, and a repeat cervical conization, respectively. About 33.3% (5/15) patients had residual lesions of low-grade CIN and above after recognization. The clinical characteristics of patients in the three groups were similar. The residual lesion rates of patients selected for follow-up, ALA-PDT, and recognization were 34.3% (12/35), 9.1% (3/33), and 0% (0/15), respectively, at 6-month follow-up (p = 0.004). The HPV clearance rates were 31.3%, 66.7%, and 84.6%, respectively (p = 0.01). Further analysis showed that a positive margin in the inscribed margin of the cervical canal (p = 0.022) and persistent HR-HPV positive tests after initial conization (p = 0.003) significantly increased the risk of residual disease. At 2-year follow-up, the recurrence rates of lesions were 3.3% and 26.1% in the ALA-PDT and follow-up groups, respectively (p = 0.021). Notably, the recurrence rates were not significantly different between the ALA-PDT and recognization groups (3.3% vs. 6.7%) (p = 0.561). CONCLUSION: ALA-PDT is an effective treatment for patients with a positive margin after cervical conization for high-grade CIN. Compared with regular follow-up, ALA-PDT can reduce residual and recurrence rate. Moreover, there was no significant difference in the efficacy between AlA-PDT and recognization.

Combined therapy of 5-aminolevulinic acid photodynamic therapy and intense pulsed light for rosacea.

Rosacea is difficult to treat. Therefore, new alternative modalities are necessary to demonstrate. The present study was conducted to assess the efficacy and safety of the combined therapy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and intense pulsed light (IPL) for rosacea to provide a new treatment option for rosacea. The study was conducted from November 2017 to April 2019 at the Department of Dermatology, The First Hospital of China Medical University. Patients aged 18-65 years and diagnosed clinically as erythematotelangiectatic (ET) or papulopustular (PP) rosacea were enrolled. Three times of ALA-PDT at 10 days interval followed by 3 times of IPL at 3-4 weeks interval were defined as 1 session and applied to the whole face of each patient. ALA-PDT: 5% ALA, red light (fluency dose 60-100 mW/cm2, 20 min); IPL: 560/590/640 nm, double/triple-pulse mode, pulse width 3.0 to 4.5 ms, delay time 30-40 ms, energy fluency 14-17 J/cm2. Ten patients were enrolled in the study. Among them, 4 patients received only 1 session, while 6 patients received 2 sessions. After all treatments, 50% of patients achieved 75-100% improvement, and 30% achieved 50-75% improvement. Forty percent of patients were graded very satisfaction and 30% graded moderate satisfaction. All noninvasive measurements showed no significant differences among all time points (p > 0.05). The side effects were pain, burning sensation, itching, erythema, desquamation, slight edema, slight exudation, and hyperpigmentation. All of which were tolerable and recovered in a few days. The combined therapy of ALA-PDT and IPL showed an effective option for rosacea with a safety profile.

[5-aminolevulinic acid photodynamic therapy for condyloma acuminata with high-risk HPV infection and local cellular immunoactivity of the patient].

OBJECTIVE: To observe the clinical effects of the 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on condyloma acuminata with high-risk human papillomavirus (HPV) infection and cellular immunoactivity in the local tissue of the patient. METHODS: From January 2015 to January 2017, we treated 47 cases of condyloma acuminata with high-risk HPV infection in our hospital by simple excision of the wart (the control group, n = 21) or 1－5 times of ALA-PDT plus wart excision (the observation group, n = 26) and observed the changes in the number of warts and recurrence at 6 months after surgery. We excised all the warts in the control group and those >5 mm before ALA-PDT and >2 mm at 48 hours after 1－5 times of ALA-PDT in the observation group, followed by examination of the counts of CD4+ and CD8+ T cells, CD4+ / CD8+ ratio, and number of CD68+ macrophages in the local tissue by immunohistochemistry. RESULTS: In the control group, the warts were completely removed in all the 21 cases but recurred in 9 (42.9%) at 6 months after surgery. In the observation group, 5 times of ALA-PDT achieved complete removal of the warts in 16 (61.5%) of the 26 patients, partial removal in 7 (26.9%), and inefficient removal in 3 (11.5%), with a total effective removal rate of 88.5% (23/26), a significantly lower 6-month recurrence rate (11.5% ï¼»3/26ï¼½) than in the control (P < 0.05), but no such severe complications as festering, scarring and pigmentation. Compared with the control group and the baseline, the observation group showed remarkable increases after 1, 3 and 5 times of ALA-PDT in the counts of CD4+ T lymphocytes (31.21 ± 6.23 and 30.27 ± 5.63 vs 56.88 ± 4.72, 54.67 ± 2.84 and 42.62 ± 2.31, P < 0.05) and CD8+ T cells (25.31 ± 3.51 and 27.35 ± 3.78 vs 48.87 ± 2.47, 45.41 ± 3.17 and 37.58 ± 3.32, P < 0.01) and the CD4+ / CD8+ ratio (1.21 ± 0.52 and 1.09 ± 0.37 vs 1.68 ± 0.52, 1.63 ± 0.45 and 1.42 ± 0.13, P < 0.05 or P < 0.01), but exhibited no significant change in the count of CD68+ macrophages in the local tissue (23.31 ± 1.54 and 20.25 ± 1.28 vs 22.31 ± 2.73, 23.17 ± 2.41 and 21.35 ± 3.72, P > 0.05). CONCLUSIONS: ALA-PDT, with its advantages of high efficiency, little invasion and high safety, is effective for the treatment of condyloma acuminata with high-risk HPV infection and it can also improve cellular immunoactivity in the local tissue and reduce recurrence.

Is the step-up therapy of topical 5-aminolevulinic acid photodynamic therapy effective and safe for the patients with recalcitrant facial flat wart?

Facial flat wart, caused by human papilloma virus type 3 and less often, type 10, 27, and 41, often brings many cosmetic problems to children and young adults. Considering the disturbing cosmetic problem, the treatment of facial flat wart is always frustrating and often unsuccessful, although there are many treatment modalities. Considering the possible serious side effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), we designed step-up therapy of ALA-PDT on different clinical phases of facial flat wart. As a new protocol of ALA-PDT, we found the step-up therapy of ALA-PDT could also receive excellent effects with the lower side effects. Meanwhile, the tolerance of patients to ALA-PDT could improve with subsequent treatment sessions and escalating doses of ALA-PDT.

The efficacy of 5-aminolevulinic acid photodynamic therapy for pediatric vulvar lichen sclerosus.

BACKGROUND: Prepubertal girls are one of the vulnerable populations of vulvar lichen sclerosus (VLS), which results in a decreased quality of life and increases risk of vulvar cancer. But the therapeutic effects of traditional topical remedies are unsatisfactory in some pediatric patients. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for refractory VLS patients, but no study has been conducted in child patients. METHODS: The patients included in this study underwent three sessions of ALA-PDT at 2-week intervals. All patients were evaluated for objective clinical appearances and subjective symptoms quantitatively. Statistical analysis comparing parameters at baseline and after three-time ALA-PDT was performed. RESULTS: A total of seven VLS girl patients were included in this study. Both primary objective appearances (lesion size and depigmentation) and subjective symptoms (itching and burning pain) were improved remarkably after the third treatment. Besides, adverse effects, mainly as pain and post-treatment edema, were mild and could be tolerated. CONCLUSIONS: ALA-PDT is an effective and safe therapeutic option for VLS girl patients. Compared with adult patients, the symptoms resolved more quickly in child patients.

Clinical efficacy analysis of 5-aminolevulinic acid photodynamic therapy for vulvar lichen sclerosus.

OBJECTIVE: The purpose of this study is to analyze the efficacy of photodynamic therapy in the treatment of vulvar lichen sclerosus who do not respond to topical glucocorticoid therapy, analyze whether there are factors that affect the efficacy, and identify adverse reactions to the treatment. METHOD: This retrospective study included 42 patients with vulval lichen sclerosis treated with ALA-PDT. Basic data of all patients were collected, and the clinical symptoms and signs of the patients before treatment were evaluated. After one year of treatment, the clinical efficacy was evaluated and analyzed whether there were any factors that affected the treatment effect. RESULT: One year after the ALA-PDT treatment, the clinical effective rate was 64.29 % (27/42), the general effective rate was 19.05 % (8/42), the ineffective rate was 4.76 % (2/42), and the recurrence rate was 11.90 % (5/42). There was no correlation between menopause, number of births given, body mass index, duration of disease, treatment times and treatment effect. For patients with severe itching and atrophy, PDT was less effective. Adverse effects were minimal and no structural complications were reported. CONCLUSION: ALA-PDT can obviously alleviate itching in VLS patients, improve skin elasticity, skin color and reduce lesion area. ALA-PDT for VLS has a low recurrence rate and few side effects.

Therapeutic and fluorescence evaluation of 20% 5-aminolevulinic acid-mediated photodynamic therapy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. METHODS: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80-100 mW/cm2) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. RESULTS: One week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment. CONCLUSION: AK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.

Combination of biopsy forceps excision and ALA-PDT for the treatment of cervical condylomata acuminata.

BACKGROUND: Human papilloma virus (HPV) infection and cervical condyloma acuminatum (CA) often co-exist. Although there are many methods to treat cervical CA, high recurrence rate and cervical scars are still troublesome. Biopsy forceps excision combined with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a feasible approach for cervical CA, but its efficacy and limitation need to be evaluated. METHODS: This retrospective study consisted of 49 patients aged 18-50 years with a histologically or colposcopic confirmed cervical CA and with HPV infection. Patients were treated with biopsy forceps excision and ALA-PDT. The efficacy was evaluated through HPV typing and colposcopy directed biopsy. RESULTS: Three months after the combination treatment the total lesion remission rate was 93.88 % (46/49) and the HPV clearance rate was 83.67 % (41/49). One patients showed some residual lesions and two patients showed new lesions. Recurrence rate was 4.34 % at 6 months follow-up. There was no significant difference in HPV clearance rate at 3 and 6 months follow-up. Univariate analysis showed that the combination treatment was less effective for patients who had size of visible lesion > 1.5 cm2. Adverse effects were minimal and no structural complications were reported. The main side effects were abdominal pain and increased vaginal secretions. CONCLUSION: Combination of biopsy forceps excision and ALA-PDT is safe and effective for eliminating cervical condylomata lesion and eradicating HPV infection. Colposcopic evaluation is recommended before and after treatment.

A prospective, split-face, randomized controlled trial of intense pulsed light-photodynamic therapy for seborrhea.

BACKGROUND: Seborrhea poses a common cosmetic concern in adolescents and young adults, often accompanied by enlarged pores, and contributing to various skin conditions, including acne vulgaris and seborrheic dermatitis. At present, there is a lack of effective treatment for this problem, and the potential of photodynamic therapy (PDT) in reducing sebum remains inconclusive. OBJECTIVE: This exploratory, prospective, single-center, double-blinded, randomized split-face controlled trial aimed to compare the efficacy and safety of intense pulsed light-photodynamic therapy (IPL-PDT) versus IPL therapy for seborrhea. METHODS: Participants with seborrhea underwent 3 times of IPL treatment (590 nm, 15-17 J/cm2 based on patient's tolerance) for one hemifacial part and IPL-PDT treatment for the other. Follow-up assessment was conducted up to 8 weeks after the final treatment. RESULTS: Compared with single IPL treatment, IPL-PDT can significantly inhibit sebum secretion and decrease pore size. PDT group exhibited no additional damage to the skin barrier, with even lower transepidermal water loss (TEWL). Additionally, the PDT group showed superior improvement in scores of porphyrins, red areas, and ultraviolet (UV) spots. Both groups experienced only mild topical adverse effects, well tolerated by the participants. CONCLUSION: IPL-PDT is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function.

Evaluation of combination of ALA-PDT and interferon for cervical low-grade squamous intraepithelial lesion (LSIL).

BACKGROUND: Cervical LSIL is a precancerous disease which requires regular follow-up. High risk patients need active interventions. Interferon and topical PDT have been used in the treatment of cervical LSIL. The aim of this study was to evaluate the combination use of topical PDT and interferon in the treatment of cervical LSIL. MATERIALS AND METHODS: A prospective study was carried out involving 159 women with cervical LSIL and high risk human papillomaviruses (hr-HPV) infection. Patients were divided into three groups. Group 1-receiving interferon suppository only, Group 2-receiving 19 mg/cm2 ALA plus post PDT interferon, and Group 3-receiving 38 mg/cm2 ALA plus post PDT interferon. The primary endpoint was pathological regression. The secondary endpoints were the HPV negative conversion rate and the adverse effects of treatment. RESULTS: At 6-12 months after PDT, for Group 1, the effective rate, CR rate and HPV negative conversion rate was 48.3 %, 43.3 % and 24.0 %, respectively. For Group 2, the effective rate, CR rate and HPV negative conversion rate were 89.3 %, 71.4 %, and 72.4 %, respectively. For Group 3, the effective rate, CR rate and HPV negative conversion rate were 91.5 %, 66.1 %, and 64.4 %, respectively, significantly higher than those of interferon only group. Two ALA dose group study showed similar efficacy. No patient experienced serious adverse effects. CONCLUSIONS: ALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL.

The Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Lichen Sclerosus: A Meta Analysis.

Background: Lichen sclerosus (LS) is a chronic inflammatory dermatosis that occurs mainly in the anogenital area and causes itching, soreness, atrophy and scarring, which may result in burying of the clitoris in females and phimosis in males. Photodynamic therapy (PDT) has been suggested during the past years as an alternative non-invasive treatment for LS, but there is still no meta-analysis to evaluate its efficacy and safety. Aims: To assess the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) for treatment of LS. Methods: We undertook a meta-analysis using the methodology of the Cochrane Collaboration and the guideline of PRISMA. A systematic literature search was carried out in PubMed, EMBASE, The Cochrane Library, WanFang Data, CBM and CNKI up to 30 June 2020. Randomized controlled trials (RCTs) were compared with ALA-PDT, corticosteroids or tacrolimus ointments for treating LS. The risk of bias for each trial was rated according to the Cochrane Handbook. Risk ratios (RR) with 95% confidence intervals (CI) were utilized to express the comparative outcomes. Results: We included 4 RCTs with a total of 184 participants. The meta-analysis showed ALA-PDT was better than topical ointments in treating LS (total effective rate: RR 1.38 [95% CI 1.19-1.60]). Conclusions: The current limited evidence supports the efficacy and safety of ALA-PDT in treating LS. The adverse reactions included pain, swelling, redness and exfoliation which would decrease with the continuing sessions of treatment. Further high-qualified RCTs of large samples are necessarily needed.

Comparative study of topical 5-aminolevulinic acid photodynamic therapy and surgery for the treatment of vulvar squamous intraepithelial lesion.

BACKGROUND: Vulvar squamous intraepithelial lesion (SIL) is a precursor lesion of vulvar squamous cell carcinoma. The current clinical treatments for vulvar SIL cause damage to the vulvar structure, chronic pain and psychological distress. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive therapy for intraepithelial lesions. The objective of this study was to compare the clinical efficacy and safety of ALA-PDT with local surgical resection for vulvar SIL. METHODS: A total of 56 patients with vulvar SIL were enrolled in this retrospective study. Among them, 16 patients received local resection and 40 patients received ALA-PDT. HPV genotyping and ThinPrep cytologic test (TCT) were used to evaluate treatment efficacy. In addition, colposcopy-directed biopsy was performed in all patients at 3-month follow-up and in patients with positive high-risk human papillomavirus (HR-HPV) and/or abnormal TCT results during the follow-up. RESULTS: At 3-month follow-up and in HSIL group the complete remission (CR) rate of the ALA-PDT group and surgery group was 90.6% (29/32) and 87.5% (14/16) (P = 1.000), respectively. The HPV clearance rate of the ALA-PDT group and surgery group was 45.2% (14/31) and 43.8% (7/16) (P = 0.927), respectively. The average numbers of ALA-PDT treatments were 5.34 for HSIL patients and 4.88 for LSIL patients, respectively. The CR rate of HSIL patients and LSIL patients was 90.6% (29/32) and 75.0% (6/8) (P = 0.550), respectively. The HPV clearance rate of HSIL patients and LSIL patients was 45.2% (14/31) and 37.5% (3/8) (P = 1.000), respectively. The ALA-PDT group showed similar clinical efficacy and milder adverse effects compared with the surgical group. CONCLUSION: ALA-PDT showed similar clinical efficacy as surgery in the treatment of vulvar SIL, but with milder adverse effects and maintaining the integrity of the vulvar structure.

5-aminolevulinic acid photodynamic therapy combined with wart curettage treatment for intractable urethral condylomata acuminata. A case report.

Condylomata acuminata (CA) is caused by human papillomavirus (HPV). It is one of the most common sexually transmitted diseases (STD). The lesions mainly occur in the external genitalia and perianal areas, rarely involves in urethral and usually localized at the distal 3 cm of the urethral orifice. Because of the special anatomical site, treating urethral CA is challenging and it has high recurrence rate after treatment. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) can successfully treat urethral CA, however, the experience of using ALA-PDT combined with wart curettage to treat intractable urethral CA is still very limited. In here, we reported an intractable urethral CA case with effective remission after receiving combination therapy. Wart curettage combine with ALA-PDT is an expeditious, economical, and well-tolerated treatment method.

Surgery plus photodynamic therapy for a diabetic patient with cutaneous infectious granuloma caused by Curvularia lunata.

Curvularia lunata (C. lunata) can be easily found in environment and plants and rarely causes human infections. Antifungal agents have been the primary approach to treat such infections; however, adverse hepatotoxic reactions may require discontinuation of the long-term use of antifungal agents in patients with pre-existing liver diseases. New therapeutic approaches are thus needed to cope with these circumstances. Here, we report a 66-year-old diabetic female patient, suffering from a rapidly growing lesion on the nose for 2 months. The patient was diagnosed with cutaneous fungal infection caused by C. lunata, which was based on mycological study and ITS sequencing. The lesion was completely disappeared after a combination of surgery and 3 times of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) at 9- day intervals. The patient did not receive any antifungal agents during the treatment. There was no recurrence at 6-month fellow-up. In the following in vitro study, C. Lunata growth was significantly inhibited by ALA-PDT treatment. Therapeutic success in this patent suggests that the ALA-PDT method could be a promising treatment for cutaneous fungal infection caused by C. Lunata and others.

5-aminolevulinic acid photodynamic therapy combined with carbon dioxide laser therapy is a safe and effective treatment for vaginal intraepithelial neoplasia.

BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a precursor of vaginal carcinoma that is often treated with CO2 laser therapy. However, recurrence after laser therapy is common, so new approaches are needed to enhance treatment effectiveness. The aim of this study was to investigate the efficacy and safety of combining 5- aminolevulinic acid photodynamic therapy (5-ALA-PDT) with CO2 laser therapy for the treatment of VaIN. METHODS: Clinical data from 40 VaIN patients who received CO2 laser therapy with or without ALA-PDT were retrospectively analyzed. Cytology, human papillomavirus (HPV) status, colposcopic images, and histopathology before and after treatment were compared, and treatment efficacy, adverse reactions, and patient prognosis were assessed. RESULTS: There was no significant difference in the cure rate between the CO2 laser group and the CO2 laser+5-ALA-PDT group after 12 months of follow-up. The difference in HPV clearance rate between the CO2 laser only group and the CO2 laser + 5-ALA-PDT group was significant at 6 and 12 months after treatment but not at 3 months after treatment. 10% patients in the CO2 laser only group experienced adverse events, while no serious adverse events were observed in the CO2 laser + 5-ALA-PDT group. CONCLUSIONS: 5-ALA-PDT combined with CO2 laser therapy appears to be a safe and effective treatment for VaIN that results in a high rate of HPV clearance with few side effects.

Efficacy and safety of microneedling, fractional CO2 laser, and cryotherapy combined with 5-aminolevulinic acid photodynamic therapy in the treatment of actinic keratosis: A multicenter prospective randomized controlled study.

BACKGROUND: Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO2 laser can facilitate the penetration of photosensitizer, while cryotherapy can treat deeper tissues but is not suitable for field cancerization. OBJECTIVE: To investigate the efficacy of microneedling, fractional CO2 laser, and cryotherapy in combination with PDT for AK. METHODS: Patients with AK were randomized into 4 groups, including group A with microneedling + PDT, group B with fractional CO2 laser + PDT, group C with cryotherapy + PDT, and group D with PDT. After 12 weeks, the clinical, dermoscopic, and reflectance confocal microscopy (RCM) outcomes were assessed. RESULTS: A total of 129 patients were included in this study, with 31, 30, 35, and 31 patients in each group, yielding clinical response rates of 90.3%, 93.3%, 97.1%, and 74.2%, respectively (P=0.026). The RCM response rates were 71.0%, 80.0%, 85.7%, and 54.8%, respectively (P=0.030). The dermoscopic response rates were 77.4%, 83.3%, 88.6%, and 60.0%, respectively (P=0.039). Group C showed the best efficacy in terms of clinical, dermoscopic, and RCM outcomes. CONCLUSIONS: All three treatments improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy.

Halofuginone enhances the anti-tumor effect of ALA-PDT by suppressing NRF2 signaling in cSCC.

BACKGROUND: 5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of skin diseases including cSCC (cutaneous squamous cell carcinoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer cells. For now, there are no published study focusing on the combination use of ALA-PDT with HL to improve clinical efficacy of cSCC. OBJECTIVE: In this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism. METHODS: The human epidermoid carcinoma cell line SCL-1 was treated with ALA-PDT or/ and HL, and cell viability, cell migration, ROS production, apoptosis were evaluated by CCK-8, colony formation, scratch assay, DCFH-DA probe, flow cytometry, respectively. The protein expression of NRF2 signaling was examined by western blot. RESULTS: HL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related ß-catenin, p-Erk1/2, p-Akt and p-S6K1 expression. Overexpression of NRF2 conferred resistance to co-treatment's effects on c-Myc, Cyclin D1, Bcl-2, as well as cell proliferation. HL also strengthened ALA-PDT's inhibition of tumor volume in cSCC mouse model and elevated ROS generation of ALA-PDT. CONCLUSION: HL enhances the anti-tumor effect of ALA-PDT in vitro and in vivo. HL has the potential to enhance the anti-tumor effect of ALA-PDT in cSCC via inhibiting NRF2 signaling.