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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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALA-PDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumor-infiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC.

• PDT is an efficient, safe, and non-invasive treatment method for VLS. • PDT treatment can be considered for VLS with ineffective topical glucocorticoid therapy. • For patients with severe itching and atrophy, PDT was less effective. Menopause status, number of birth given, BMI, and duration of disease did not affect treatment outcomes. 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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

• Photodynamic therapy is effective for vulvar lichen sclerosus girl patients. • The symptoms resolved more quickly in child patients than adult patients. • Adverse effects were tolerable, mainly pain and post-treatment edema. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

• This prospective study investigated the efficacy of intravaginal interferon alone a nd ALA-PDT combined with interferon in the treatment of cervical LSIL, and initially explored the effect of different ALA doses on the efficacy. • The combination of cervical ALA-PDT and post-PDT use of intravaginal interferon was feasible and tolerable. • Two ALA doses were used in this study and both showed similar outcomes in treating cervical LSIL. 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. 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. 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. ALA-PDT combined with interferon therapy was feasible and tolerable. Two ALA dose groups showed similar outcomes in treating cervical LSIL. [ABSTRACT FROM AUTHOR]

• ALA-PDT is an effective and safe alternative treatment for vulvar SIL and its effect is unaffected by the grade of lesions. • Comparing with surgical resection, ALA-PDT shows advantages of less trauma, fewer adverse reactions and rapid functional recovery. • ALA-PDT is more suitable for the treatment of multisite vulvar lesions. 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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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., (© 2023 Wiley Periodicals LLC.)

• Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. PDT monotherapy resulted in a clinical response rate of 74.2%, while combination therapy with microneedling, fractional CO 2 laser, and cryotherapy yielded clinical response rates of 90.3%, 93.3%, and 97.1%, respectively (P = 0.026). All three combination treatments (microneedling, fractional CO 2 laser, and cryotherapy) improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy. Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO 2 laser can facilitate the penetration of photosensitizer, while cryotherapy can treat deeper tissues but is not suitable for field cancerization. To investigate the efficacy of microneedling, fractional CO 2 laser, and cryotherapy in combination with PDT for AK. Patients with AK were randomized into 4 groups, including group A with microneedling + PDT, group B with fractional CO 2 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. 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. All three treatments improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy. [ABSTRACT FROM AUTHOR]

• This is the first report about severe hypertrophic scar induced by facial hidradenitis suppurativa (HS). • 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) is an effective non-invasive therapy targeted to hidden infections. • The treatment combined with peel-off and high concentration single-dose 5-ALA PDT is a recommended for severe facial hypertrophic scar induced by HS. Hidradenitis suppurativa (HS) is a type of chronic suppurative inflammatory reaction of the hair follicles characterized by recurrent dermal abscesses, sinus tracts and scars. In this report, one case of severe hypertrophic scar induced by facial HS achieved resolution of skin lesions after combined treatment with high concentration single-dose 5-aminolevulinic acid photodynamic therapy (5-ALA PDT). No recurrence was observed up to eleven months of follow-up. The 5-ALA PDT based treatment could improve the severe hypertrophic scar induced by HS in an effective and safe manner. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO 2 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 CO 2 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 CO 2 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., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Background The effect of 5-aminolevulinic acid photodynamic therapy on keratinocyte proliferation and apoptosis in condyloma acuminatum tissues was evaluated. Methods An immunohistochemical method and TdT-mediated dUTP nick end labeling were performed to detect the positive expression of the keratinocyte proliferation-related gene Ki-67 and apoptosis, respectively, in condyloma acuminatum tissues. Results Of 52 cases, 44 showed positive expression of Ki-67 in condyloma acuminatum keratinocytes before the treatment, with a positive expression rate of 84.62% (44/52), an expression strength of mostly ++ − +++, and a Ki-67 proliferation index of 80.26 ± 5.07%. After treatment, 22 cases showed positive expression of Ki-67 in condyloma acuminatum keratinocytes, with a positive expression rate of 42.31% (22/52), an expression strength of mostly − − ++, and a proliferation index of 42.67 ± 3.06%. The differences in the positive expression rate, expression strength, and proliferation index in the before- and after-treatment groups were statistically significant ( χ 2 = 20.070, P < 0.001). For visible apoptotic cells in condyloma acuminatum keratinocytes before the 5-aminolevulinic acid photodynamic treatment, the expression strength was mostly + − ++, and the average apoptotic index was 13.94 ± 2.35%; after treatment, the expression strength was mostly ++ − +++, and the average apoptotic index was 73.88 ± 7.65%; the difference in the apoptotic index between the before and after treatment groups was statistically significant ( P < 0.001). Conclusion 5-Aminolevulinic acid photodynamic therapy can inhibit the proliferation and promote the apoptosis of keratinocytes, and represents an effective mechanism for treating condyloma acuminatum. [ABSTRACT FROM AUTHOR]

• Condylomata acuminata occurred in the urethra is uncommon. • ALA-PDT combined with wart curettage treatment were effective in intractable urethral CA patient. • Wart curettage treatment before ALA-PDT can improve the therapeutic effect of PDT and reduce side-effects. 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. [ABSTRACT FROM AUTHOR]

• 5-ALA-PDT combined with CO 2 laser therapy is a safe and effective treatment for VaIN that results in a high rate of HPV clearance with few side effects. • Our findings suggest that treatment of high vaginal intraepithelial lesions with CO 2 laser therapy and 5-ALA-PDT under colposcopy guidance is safe and effective, and can lead to disease cure and clearance of HPV infection in most patients. Vaginal intraepithelial neoplasia (VaIN) is a precursor of vaginal carcinoma that is often treated with CO 2 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 CO 2 laser therapy for the treatment of VaIN. 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. 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 CO 2 laser only group and the CO 2 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 CO 2 laser only group experienced adverse events, while no serious adverse events were observed in the CO 2 laser + 5-ALA-PDT group. 5-ALA-PDT combined with CO 2 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. [ABSTRACT FROM AUTHOR]

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is a method using a photosensitizer and light radiation for disease treatment, and is currently used for the treatment of skin cancers, precancerous lesions and viral warts. The present study aimed to investigate the effect of ALA-PDT on human cervical cancer through the regulation of microRNA-143 (miR-143) and the Bcl-2/Bax signaling pathway. The results demonstrated that ALA-PDT reduced proliferation, increased cytotoxicity and induced apoptosis in HeLa human cervical carcinoma cells. Reverse transcription-quantitative polymerase chain reaction analysis demonstrated that the expression levels of miR-143 were increased following ALA-PDT treatment. Western blotting indicated that the expression levels of Bcl-2 and Bax were significantly reduced and increased, respectively, by ALA-PDT treatment. In addition, upregulation of miR-143 expression reduced Bcl-2 expression and increased Bax expression in HeLa cells. However, downregulation of miR-143 expression inhibited the effect of ALA-PDT on Bcl-2/Bax protein expression. In conclusion, the current study demonstrated that ALA-PDT affected human cervical cancer via the activation of miR-143 and the suppression of the Bcl-2/Bax signaling pathway. [ABSTRACT FROM AUTHOR]

• ALA-PDT is an effective, safe and alternative treatment for cervical HSIL. • Positive HR-HPV E6/E7 mRNA affects the effect of ALA-PDT for cervical HSIL. • ALA-PDT is inapplicable to those with persistently positive E6/E7 mRNA before and after treatment. E6 and E7 high-risk human papillomavirus (HR-HPV) oncoproteins are closely associated with the initiation and progression of cervical cancer (CC) and pre-cancerous lesions. Cervical high-grade squamous intraepithelial lesions (HSIL), as pre-cancerous lesions, have a 5% chance of progressing to invasive cancer. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel non-invasive targeted therapy for intraepithelial lesions. Herein, we analyzed the effect of HR-HPV E6/E7 mRNA on ALA-PDT for cervical HSIL. A retrospective analysis of 148 HR-HPV-positive patients diagnosed with cervical HSIL and receiving ALA-PDT was carried out. ALA-PDT was performed with 20% ALA thermosensitive gel, and irradiation at wavelength of 635 nm and density of 80–100 J/cm2 for 20–30 min. The therapeutic instruments of LED and semiconductor laser were applied for cervical lesions and lesions in endocervical canal, respectively. All patients were tested for HPV E6/E7 mRNA before and after PDT, and then followed up at 3, 6, and 12 months after treatment, and every six months thereafter. At the 6-month follow up, the complete remission (CR) rate of patients' lesions was 86.5% (128/148), whereas the total HPV clearance rate was 72.3% (107/148). It was evident that positive E6/E7 mRNA before treatment had a significant effect on HPV clearance rate (66.3% VS 81.4%, P = 0.045) and CR rate (80.9% VS 94.9%, P = 0.015). The E6/E7 mRNA associated with HPV16/18 and HPV16/18 combined with other HR-HPV (HPV16/18 and other HR-HPV) affected HPV clearance (P = 0.035) and lesions CR (P = 0.039), respectively. Moreover, persistently positive E6/E7 mRNA after treatment was closely associated with poor efficacy (HPV clearance rate: P = 0.000, CR rate: P = 0.000). Throughout the follow up period, two cases recurred but none of the patients progressed. This study has shown that ALA-PDT is an effective, safe, and alternative treatment for cervical HSIL, especially for the patients of childbearing age. However, its efficacy is relatively poor in patients with persistently positive E6/E7 mRNA before and after treatment, who are relatively insensitive to ALA-PDT. [ABSTRACT FROM AUTHOR]

• 5-Aminolevulinic acid (5-ALA) photodynamic therapy (PDT) is effective in the treatment of high-grade vaginal intraepithelial neoplasia (VAIN), and there was no significant difference in the efficacy compared with surgical excision. • 5-ALA-PDT has no serious adverse reactions and can maintain the structural and functional integrity of the target organ, which is safer than surgical excision. • 5-ALA-PDT has more advantages in the treatment of multifocal and dispersive lesions compared to surgical excision. To compare the clinical efficacy and safety of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and local surgical excision in the treatment of high-grade vaginal intraepithelial neoplasia (VAIN). This was a retrospective study of a single center. Patients with biopsy-proven high-grade VAIN were counseled on the option of excision or ALA-PDT. After treatment patients were followed up at 3, 6 and 12 months and every 6 months afterwards. Clinical data of two groups were analyzed. Sixty patients were treated with ALA-PDT and 40 patients underwent excision surgery. The clinical characteristics of patients in the two groups were similar. The mean ages of patients treated with ALA-PDT and local surgical excision were 41.93+13.08 (18-70) and 43.25+11.64 (22–61) years old, respectively. The treatment times of PDT for patients in the ALA-PDT group were 5.48±1.41 (2-8) times. At 3–6 months after treatment, the overall complete remission (CR) rate was 93.33% (56/60) in PDT group and 82.5% (33/40) in local surgical excision group. In PDT group , a 12- and 24-month follow-up, the total HPV clearance rate was 68.97% and 77.55%, respectively. At 12-month and 2-year follow-up after local surgical excision, the total HPV clearance rate was 60% and 64.52%, respectively. Further analysis showed that the clinical efficacy was comparable between the two treatments. Patients over 45 years old exhibited a lower HPV clearance rate (P <0.05) than those under 45 years old. It was also observed that persistent HPV infection is a major risk factor for persistent disease. Further comparative analyses showed no significant difference in the CR rate and treatment times between VAINII and VAINIII in ALA-PDT group. Moreover, 4 patients (11.36%) developed recurrent lesions during follow-up after ALA-PDT, whereas 3 patients (8.33%) in the local excision group developed recurrent lesions. In addition, there was no significant difference in the recurrent rate between two groups. ALA-PDT shows similar efficacy and less side effects compared to local surgical excision. [ABSTRACT FROM AUTHOR]

• Condyloma Acuminatum in Special Sites can not be ignored. • Cryotherapy for pretreatment is likely to improve the effects of PDT. • Cryotherapy combined with ALA-PDT may be superior to traditional therapy and topical drugs in clinical treatment. Condyloma acuminatum is a benign tumor principally resulting from a human papillomavirus type 6 or 11 infection. The lesions mostly damage the genital and perianal squamous epithelium and skin but occasionally emerge outside the perianal and genital regions. We studied the cases of a 29-year-old man with left nasal vestibule vegetation and a 22-year-old woman with left nipple vegetation. Each was diagnosed with condyloma acuminatum by histopathological examination and a human papillomavirus DNA test. The two patients received cryotherapy combined with 5-aminolevulinic acid photodynamic therapy and experienced no relapses during follow-up. These results suggest that physicians cannot ignore condyloma acuminatum outside the perianal and genital regions during diagnosis and treatment. Additionally, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy is not only safe and effective for the treatment of condyloma acuminatum in special sites, but it is also less destructive to the affected regions. Thus, cryotherapy combined with 5-aminolevulinic acid photodynamic therapy may have more advantages than traditional therapy in the treatment of condyloma acuminatum in special sites. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• ALA-PDT is an effective, safe and alternative treatment for HR-HPV positive VAIN. • Age, HPV subtype, history of hysterectomies affect the effect of ALA-PDT for VAIN. • ALA-PDT treats VAIN without damaging the structure and function of tissues. Recent data has shown increased rate of vaginal intraepithelial neoplasia (VAIN) in younger individuals. Traditional VAIN treatments exert adverse effects on the anatomy and functions of the vagina. Topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a novel, non-invasive targeted therapy for intraepithelial lesions. Here, we aimed to investigate the efficacy and safety of ALA-PDT in VAIN with high-risk HPV (HR-HPV) infection. This study enrolled a total of 82 HR-HPV-positive women diagnosed with VAIN, who were receiving ALA-PDT. The effect of ALA-PDT was evaluated using HPV genotyping and Thinprep cytologic test (TCT). Besides, colposcopy directed biopsies were performed in all patients at 3-month follow-up, and in patients with positive HR-HPV and/or abnormal TCT results during the follow-up period. Our data showed that the HPV clearance rate was 53.7% (44/82) at 6-month follow-up and 67.1% (55/82) at 12-month follow-up. Patients with HPV16/18 combined with other HR-HPV (HPV16/18 & other HR-HPV) infection, those with a history of hysterectomy and/or older age were had significantly lower HPV clearance rate. Besides, the lesion complete remission (CR) rate was 90.2% (74/82). These results show that HPV16/18 & other HR-HPV infection was associated with significantly lower CR rates. Throughout the follow-up, 2 cases had persistent lesions (2.4%), 6 cases had partial remission (7.3%), 2 cases recurred (2.7%) but none of the patients had disease progression. Taken together, our data showed that ALA-PDT is an effective, safe, and alternative treatment for VAIN patients with HR-HPV infection. However, the ALA-PDT efficacy was relatively poor in patients with older age, HPV16/18 & other HR-HPV infection and/or those with a history of hysterectomy. [ABSTRACT FROM AUTHOR]

Lesions in both the cervix and vagina require an efficacious non-invasive treatment therapy such as 5-Aminolevulinic acid photodynamic therapy(5-ALA-PDT). In this study, we evaluate clinical efficacy and safety of 5-ALA PDT for cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia (CIN & VAIN). A retrospective analysis was performed on 48 patients diagnosed with CIN & VAIN and receiving 5-ALA PDT. All patients were first followed up at 3, 6 and 12 months after treatment, then every 6 months thereafter. Out of 1051 patients referred for CIN (4.56%), 48 were diagnosed with CIN&VAIIN. The patients had statistically significant average vaginal and cervical lesion areas of 1.22 and 0.41 cm2 respectively. 4 patients were lost during follow-up. The patients' complete remission (CR) rate was 88.64% (39/44) at 3–6 months after treatment, while the total HPV clearance rate was 46.34 and 60.98% at 3- and 12-months follow-up,respectively. HPV16/18 combined with other high-risk human papillomaviruses (hrHPV) (HPV16/18 and other hrHPV) infection exhibited a lower HPV clearance rate (P = 0.006). The treatment time in high-grade intraepithelial neoplasia (HSIL) was higher than that of low-grade intraepithelial neoplasia (LSIL). Notably, atypical vessels and endocervical canal lesions involvement significantly affected 5-ALA PDT. Moreover, 5 patients had residual lesions (11.36%) during follow-up, one patient presented recurrence (2.56%), while 4 had successful pregnancy. 5-ALA-PDT is a non-invasive, effective, and safe therapy for treating CIN & VAIN and can maintain the structural and functional integrity of target organs. However, its efficacy is relatively poor in patients with endocervical canal lesions involvement, atypical vessels, and HPV16/18 and other hrHPV infection. • 5-Aminolevulinic acid (5-ALA) photodynamic therapy(PDT) can simultaneously treat cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia(VAIN). • 5-Aminolevulinic acid (5-ALA) photodynamic therapy(PDT) has no serious adverse reactions and can maintain the structural and functional integrity of the target organ. It is a good choice especially for patients with fertility requirements. • 5-Aminolevulinic acid (5-ALA) photodynamic therapy(PDT) had a long-term effect on HPV clearance. • For patients with endocervical canal lesions involvement or atypical blood vessels, the effect of 5-Aminolevulinic acid (5-ALA) photodynamic therapy(PDT) was relatively poor. [ABSTRACT FROM AUTHOR]

• This study explored the possible mechanisms of ALA-PDT in the treatment of CA. • CA tissues before and at one week after treatment were examined. • TRL4 and NF-κB expression in the keratinocytes of CA after treatment were evaluated. • ALA-PDT relieved the local immuno-suppressive state in the keratinocytes. Condyloma acuminatum (CA) is a common sexually transmitted disease caused by human papillomaviruses. Five-aminolevulinic acid-photodynamic therapy (ALA-PDT) can promote the apoptosis of keratinocytes and inhibit proliferation; however, the effect of ALA-PDT on the immune mechanism of CA tissue is not well understood. In this study, we examined the changes in Toll-like receptor 4 (TRL4) and nuclear factor kappa B (NF-κB) expression in CA tissues before ALA-PDT treatment to determine its effects and possible immune mechanisms. Immunohistochemistry (streptavidin-peroxidase) was used to detect the expression of TLR4 and NF-κB in the keratinocytes of the patients with CA before and after ALA-PDT treatment. Before treatment, the positive TLR4 and NF-κB expression rates in the keratinocytes of the patients with CA were 86.53% (45/52) and 94.23% (49/52), respectively, whereas after treatment, these rates were 44.23% (23/52) and 38.46% (20/52), respectively. Positive TLR4 and NF-κB expression in the keratinocytes of CA was mostly ++ to +++ in intensity before ALA-PDT and mostly ranged from – to + after treatment. The positive expression rate and intensity of TLR4 and NF-κB in the two groups before and after ALA-PDT were significantly different (P < 0.05). There was a positive correlation between the expression of TLR4 and NF-κB in the CA tissues after ALA-PDT (r = 0.486, P < 0.05). ALA-PDT may relieve local immunosuppressive states by reducing TLR4 and NF-κB expression and jointly promoting CA regression, which is a potential molecular mechanism of ALA-PDT in CA treatment. [ABSTRACT FROM AUTHOR]

• Halofuginone enhances the anti-tumor effect of ALA-PDT in cSCC. • Halofuginone enhances the anti-tumor effect of ALA-PDT via NRF2 signaling. • Halofuginone combined ALA-PDT may assist in cSCC therapy. 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. In this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism. 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. HL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related β-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. 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. [ABSTRACT FROM AUTHOR]

• Condylomata acuminata occurred in the urethra is uncommon. • ALA-PDT combined with holmium laser were effective even in patients with almost whole-urethral CA. Condylomata acuminata (CA) caused by human papillomavirus, often involves the external genitalia, perianal skin, and other moist mucous membranes. Urethral involvement is uncommon and little recognized, and usually limited to the distal 3 cm of the meatus. It is difficult to treat CA involving the urethra because of the anatomical location, risk of complications and recurrence. One effective method for the treatment of CA located at the urinary meatus is 5-aminolevulinic acid photodynamic therapy (ALA-PDT). However, experience of using this method for the treatment of whole urethral CA is still very limited. Herein, we treated a whole urethral CA successfully with photodynamic and holmium laser therapies. The case of a 25-year-old patient who underwent kidney transplant effected by intraurethral CA is presented and discussed. Catheter implantation and (or) immunosuppression treatment increases the risk of urethral condyloma acuminatum. The ALA-PDT is a safe, straightforward, effective, and well-tolerated treatment procedure for intraurethral CA. ALA-PDT combined with holmium laser treatment can successfully treat kidney transplant patients with intraurethral CA. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALA-PDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumor-infiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC., Competing Interests: The authors declare no conflict of interest in this work., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

• Verruca plana is a huge cosmetic burden for mainly adolescents and young adults. • Using whole-face approach, ALA-PDT can target the entire affected area, which may help wiping out latent or subclinical HPV infection. • All lesions cleared out 1 month after the last ALA-PDT session. Follow-up of at least 12 months was carried out in this study. 4 out 6 cases remained relapse-free at the end of follow-up. Verruca plana, also known as flat wart, is a common viral skin infection by human papillomavirus types 3, 10, 28 and 41. It's mostly prevalent on the facial area of children and young adults, becoming a heavy cosmetic burden on these patients. In this study, we report 6 cases of verruca plana predominantly affecting the visage, which are treated with 10% 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). In general, all 6 patients showed complete clearance of lesions 1 month after treatment. And clearance of lesions sustained in 4 out of 6 patients for at least 12 months after treatment. The results of this study suggest that ALA-PDT could be an effective treatment modality for verruca plana, especially for cases recalcitrant to other treatments. Nevertheless, more measures should be taken to prevent PDT-related adverse events. [ABSTRACT FROM AUTHOR]

• Topical ALA photodynamic therapy is an effective and minimally invasive modality for actinic cheilitis, skin squamous cell carcinoma in situ and skin microinvasive squamous cell carcinoma (Already know). • Photofrin/Foscan-mediated photodynamic therapy was demonstrated good effect for early-stage superficial oral or lip SCC. However, it requires a period of controlled light exposure for 2–4 weeks (Already know). • Topiacl ALA photodynamic also achieved good effect for early-stage lip SCC (Tis-T2N0M0) and requires little light precautions (Newly added). • Topical ALA-PDT can preserve structure and esthetic function (Newly added). Squamous cell carcinoma (SCC) of the lip removed by surgery may cause lip dysfunction and scar. ALA-PDT (5-Aminolevulinic acid photodynamic therapy) is a minimally invasive treatment for superficial SCC in situ. However, few studies reported the use of topical ALA-PDT to manage lip SCC. Between 2015 and 2017, 6 patients with Tis to T2 lip squamous cell carcinoma without evidence of lymph node spread, were treated with topical ALA-PDT at Shanghai Skin Disease Hospital. Clinical responses and side effect were evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) at 1 month, 6 months, 12 months and 24 months after ALA-PDT. All of the 6 patients achieved complete response (CR) by 2–7 sessions of ALA-PDT. There was no relapse during 24 months follow up for 4 patients. Two out of 6 patients relapsed at 10 months and 20 months post PDT but achieved CR again by 1–3 more sessions of PDT. There was no functional or aesthetic problem. Topical 5-Aminolevulinic acid photodynamic could be considered a potential alternative therapeutic option for early-stage lip squamous cell carcinoma without lymph node spread. [ABSTRACT FROM AUTHOR]

• M-PDT inhibits cSCC cell proliferation by activating p-JNK, p-p38 and inhibiting p-Erk1/2. • M-PDT inhibits cSCC cell proliferation by inhibiting PP5 and demethylation/phosphorylation of PP2A. • M-PDT inhibits cSCC cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway. We previously demonstrated that M-PDT is painless and effective in precancerous skin diseases treatment. However, whether M-PDT is effective in cSCC and the underlying inhibitory mechanism remains enigmatic. We aims to unveil the effect of M-PDT on cSCC cell proliferation and the regulatory effect of M-PDT on MAPK signaling. The proliferation and migration of cSCC cells were revealed by CCK8 assay, tumor sphere formation assay and scratch assay respectively. The expression of MAPKs was examined by western blot. The activity of PP2A and PP5 was regulated by inhibitor and recombinant adenoviruses. Here, we show that M-PDT inhibits cSCC cell proliferation by activating p-JNK, p-p38 and inhibiting p-Erk1/2, as well as activation of PP2A and inactivation of PP5. Furthermore, pharmacological inhibition of PP2A conferred resistance to M-PDT's suppression on p-Erk1/2 and attenuated inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP2A showed the contrary results. Pharmacological inhibition of PP5 potentiated M-PDT's elevation on p-JNK and strengthened inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP5 exhibited the contrary results. Our findings indicate that M-PDT inhibits cSCC cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

• In this study, we added dermoscopic assessments for the outcomes of 5-Aminolevulinic acid photodynamic therapy for vulvar lichen sclerosus. • Our study reveals that after sessions of 5-Aminolevulinic acid photodynamic therapy for vulvar lichen sclerosus, the dermoscopic features related with improved clinical manifestations were also improved. • Dermoscopic assessment may be useful to monitor the response to treatments for indicating minute changes invisible to unaided eyes, such as vessels, white shiny streaks, and follicular plugs. To date, there have been no satisfactory treatments to cure vulvar lichen sclerosus (LS). 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been introduced in the treatment of vulvar lichen sclerosus (VLS), but no dermoscopic assessment has been conducted. The included patients received six ALA-PDT sessions at 2-week intervals. After the third and sixth treatment, all patients were evaluated for clinical and dermoscopic variables with numeric scores assigned to each parameter. Twenty-four VLS patiens were included in this study. Both primary objective signs (lesion size and depigmentation) and subjective symptoms (itching and burning pain) were improved remarkably after the third treatment, and further improvements were obtained after the sixth treatment. Among the dermoscopic variables, the early changes were the decreased score of bright white or white-yellowish structureless areas and the increased score of vessels, and further changes of these two dermoscopic features were observed after the sixth treatment. There were no changes in pink structureless areas, white shiny streaks, follicular plugs, brown structureless areas, purple dots, and erosions after the third treatment, but after the sixth treatment, the scores of these dermoscopic features decreased significantly except that the score of brown structureless areas increased siginificantly. There was no change in the score of peppering blue-gray dots. Both pain and erosions during the treatment could be tolerated. ALA-PDT is effective for VLS. In addition, dermoscopic assessment may be more precise for indicating minute changes invisible to unaided eyes which are useful to monitor the response to treatments. [ABSTRACT FROM AUTHOR]

• Exploring PTCH1 mutations responsible for NBCCS. • ALA-PDT and excision surgery have a good respond to the NBCCS. • The results broaden the spectrum of PTCH1 mutations responsible for NBCCS. This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS. [ABSTRACT FROM AUTHOR]

• Pretreatment with toenail shinning combined with 5-ALA photodynamic therapy was an effective therapy for onychomycosis. • Shinning toenails with a nail file promoted the penetration depth of 5-ALA, and then enhancing the efficacy of therapy. • For onychomycosis, the combined therapy was low cost, convenient, feasible and worth promoting. Onychomycosis is the most common nail disease. There are various treatments available, the majority of which are topical and systemic therapies. However, the poor nail penetration, systemic side effects and the poor compliance of the patients lead to limited efficacy. Photodynamic therapy may be an option. Yet, the penetration of photosensitizer into the nail plate needs to be improved. Here, we report a case of onychomycosis successfully treated with 20 % 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). Toenail thinning with a common nail file was given before PDT. This suggest that thinning toenails, combining with topical ALA-PDT may be an effective, feasible, and safe alternative for the treatment of onychomycosis, especially for cases recalcitrant or inappropriate to other conventional therapies. [ABSTRACT FROM AUTHOR]

Perifolliculitis capitis abscedens et suffodiens (PCAS), also known as dissecting cellulitis of the scalp (DCS), is a rare, chronic, suppurative inflammatory disease of the scalp which may evolve into cicatricial alopecia. Its refractory nature has a detrimental impact on patients' quality of life. Here, we report five cases of PCAS treated with 5% 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT), prior to which different methods of surgical intervention were given. The surgical interventions were under local anesthesia. In general, all surgical interventions, pretreatments and PDT were well tolerated. 4 patients showed complete clearance of lesions and 1 patient attained significant improvement of symptoms 1 month after treatment. This suggested that surgical interventions, combined with topical ALA-PDT could be an effective, minimally-invasive, and safe alternative for PCAS, especially for cases recalcitrant to other conventional therapies. [ABSTRACT FROM AUTHOR]

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% ［3/26］) 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.