Lasers in Surgery and Medicine

Comparison of Topical 5‐Aminolevulinic Acid Photodynamic Therapy With the Loop Electrosurgical Excision Procedure for Patients With Cervical High‐Grade Squamous Intraepithelial Neoplasia: A Prospective and Propensity‐Matched Analysis

ABSTRACTObjectiveTo evaluate the efficacy of 5‐aminolevulinic acid photodynamic therapy (PDT) for high‐grade squamous intraepithelial lesions of the cervix associated with high‐risk human papillomavirus (HPV) infection.MethodsIn this study, 120 patients who received treatment for high‐grade squamous intraepithelial lesions of the cervix from March 2023 to March 2024 were followed up prospectively, which were categorized into the PDT and loop electrosurgical excision procedure (LEEP) groups and matched 1:1 using a propensity score. The regression rate of the lesions and the HPV clearance rate were compared between the groups at 6 and 12 months. Factors affecting the clearance rate were analyzed.ResultsAt the 6‐ and 12‐month follow‐ups, no significant difference was observed in the rate of lesion regression between the PDT (86.7%, 91.7%) and LEEP groups (85.0%, 93.3%) (p > 0.05), nor the HPV clearance rate (55.0%, 76.7% vs. 65.0%, 78.3%) (p > 0.05). Neither group had any lesions that progressed to Grade 3 or invasive cervical carcinoma at follow‐up. According to regression analysis, thinprep cytology test (TCT) results influenced lesion regression in the PDT group.ConclusionCompared to the LEEP, 5‐aminolevulinic acid PDT had a similar rate of lesion regression and HPV clearance for the treatment of high‐grade squamous intraepithelial lesions of the cervix; thus, PDT offers an alternative and effective minimally invasive approach.

Photodetection and Safety of 5‐Aminolevulinic Acid‐Induced Porphyrin in Patients With Cervical Intraepithelial Neoplasia

Background and Objectives5‐Aminolevulinic acid (5‐ALA) is a porphyrin‐based photosensitizer and has been used for photodynamic therapy of cervical intraepithelial neoplasia (CIN). In this study, photodetection and safety of 5‐ALA‐induced porphyrin in CIN tissues were assessed.Study Design/Materials and MethodsA total of 42 patients for whom colposcopy or loop electrosurgical excision procedure (LEEP) was planned were administered 10%, 20%, or 30% 5‐ALA locally on the surface of the cervix for 1.5–18 hours. At different times after application, the fluorescence intensity of 5‐ALA‐induced porphyrin on CIN and non‐CIN lesions of the cervix was detected.ResultsFluorescence intensity was correlated with drug concentration and application time. With 20% 5‐ALA, the porphyrin fluorescence intensity increased over time, reaching a peak after 6 hours of application intervals in CIN. There was no significant difference in fluorescence intensity between CIN lesions and chronic cervicitis (benign tissue) or among CIN lesions of different severities. Three adverse events were considered related to the drug; however, these had no significant correlation with the drug concentration or application time.Conclusions5‐ALA at 10%–30% concentration is safe in patients with CIN. For further treatment, we recommend the application of 20% 5‐ALA, 6 hours before photodynamic therapy in CIN.Clinical Trial RegistrationThis study was registered at http://www.chinadrugtrials.org.cn (registration number: CTR20130326) in accordance with the requirements of the National Medical Products Administration in China. Considering that there is no English version of the above website, we made a retrospective registration on http://www.chictr.org.cn (registration number ChiCTR1800016755) in 2018. Lasers Surg. Med. © 2020 Wiley Periodicals LLC

Efficacy of a New Therapeutic Option for Vulvar Intraepithelial Neoplasia: Superficial Shaving Combined With Photodynamic Therapy

Background and ObjectiveVulvar intraepithelial neoplasia (VIN), a precancerous lesion, is difficult to treat by excision or ablation due to high recurrence rates. Photodynamic therapy (PDT) is a minimally invasive therapeutic procedure and is now widely used to treat non‐melanoma skin diseases. However, the clinical response rates of VIN to single PDT are unstable. The reason may be the limited light penetration into deep tissues. Objective: To retrospectively evaluate the clinical response and recurrence of VIN after combined treatment with superficial shaving and PDT.Study Design/Materials and MethodsSeventeen patients with VIN were enrolled. All patients had multifocal high‐grade VIN that had failed to respond to various therapies. Superficial shaving was performed only once and prior to the first 5‐aminolaevulinic acid (5‐ALA)‐PDT cycle. Generally, the procedure of 5‐ALA PDT for each patient was performed in three sessions. Clinical response, recurrence, cosmetic outcomes, adverse events, patient satisfaction, quality of life, and mental health were assessed. The expression of p16 and Ki‐67 in pre‐ and post‐treatment tissue was detected.ResultsA clinical response of 94% was observed in 17 patients, who were administered combination therapy, over an observation period of 12 months. Approximately, 71% of patients had excellent cosmetic outcomes. All patients had satisfactory therapeutic effects and significant improvements in quality of life and mental health. Downregulation of p16 and Ki‐67 may have been correlated with recurrence after 5‐ALA‐PDT.ConclusionCombined treatment with superficial shaving and 5‐ALA‐PDT is a safe and effective option for VIN. In particular, combination therapy is recommended for patients with large, multifocal, high‐grade lesions; repeated recurrence; and strong willingness to maintain vulvar configuration and function. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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

AbstractBackground and ObjectiveTo 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 MethodsA 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.ResultsThirty‐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).ConclusionALA‐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.

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

AbstractBackgroundThe 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.MethodsA 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.ResultsThe 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.ConclusionsWithin 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.

Fluorescence and Multiphoton Imaging for Tissue Characterization of a Model of Postmenopausal Ovarian Cancer

Background and ObjectivesTo determine the efficacy of targeted fluorescent biomarkers and multiphoton imaging to characterize early changes in ovarian tissue with the onset of cancer.Study Design/Materials and MethodsA transgenic TgMISIIR‐TAg mouse was used as an animal model for ovarian cancer. Mice were injected with fluorescent dyes to bind to the folate receptor α, matrix metalloproteinases, and integrins. Half of the mice were treated with 4‐vinylcyclohexene diepoxide (VCD) to simulate menopause. Widefield fluorescence imaging (WFI) and multiphoton imaging of the ovaries and oviducts were conducted at 4 and 8 weeks of age. The fluorescence signal magnitude was quantified, and texture features were derived from multiphoton imaging. Linear discriminant analysis was then used to classify mouse groups.ResultsImaging features from both fluorescence imaging and multiphoton imaging show significant changes (P < 0.01) with age, VCD treatment, and genotype. The classification model is able to classify different groups to accuracies of 75.53%, 69.53%, and 86.76%, for age, VCD treatment, and genotype, respectively. Building a classification model using features from multiple modalities shows marked improvement over individual modalities.ConclusionsThis study demonstrates that using WFI with targeted biomarkers, and multiphoton imaging with endogenous contrast shows promise for detecting early changes in ovarian tissue with the onset of cancer. The results indicate that multimodal imaging can provide higher sensitivity for classifying tissue types than using single modalities alone. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.