Photodynamic anticancer activity evaluation of novel 5-aminolevulinic acid and 3-hydroxypyridinone conjugates.

5-Aminolevulinic acid (ALA) and its derivatives, serving as the endogenous precursor of the photosensitizer (PS) protoporphyrin IX (PpIX), successfully applied in tumor imaging and photodynamic therapy (PDT). ALA and its derivatives have been used to treat actinic keratosis (AK), basal cell carcinoma (BCC), and improve the detection of superficial bladder cancer. However, the high hydrophilicity of ALA and the conversion of PpIX to heme have limited the accumulation of PpIX, hindering the efficiency and potential application of ALA-PDT. This study aims to evaluate the PDT activity of three rationally designed series of ALA-HPO prodrugs, which were based on enhancing the lipophilicity of the prodrugs and reducing the labile iron pool (LIP) through HPO iron chelators to promote PpIX accumulation. Twenty-four ALA-HPO conjugates, incorporating amide, amino acid, and ester linkages, were synthesized. Most of the conjugates, exhibited no dark-toxicity to cells, according to bioactivity evaluation. Ester conjugates 19a-g showed promoted phototoxicity when tested on tumor cell lines, and this increased phototoxicity was strongly correlated with elevated PpIX levels. Among them, conjugate 19c emerged as the most promising (HeLa, IC50 = 24.25 ± 1.43 µM; MCF-7, IC50 = 43.30 ± 1.76 µM; A375, IC50 = 28.03 ± 1.00 µM), displaying superior photodynamic anticancer activity to ALA (IC50 > 100 µM). At a concentration of 80 µM, the fluorescence intensity of PpIX induced by compound 19c in HeLa, MCF-7, and A375 cells was 18.9, 5.3, and 2.8 times higher, respectively, than that induced by ALA. In conclusion, cellular phototoxicity showed a strong correlation with intracellular PpIX fluorescence levels, indicating the potential application of ALA-HPO conjugates in ALA-PDT.

Combined versus conventional photodynamic therapy with 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) for actinic keratosis: A randomized, single-blind, prospective study.

BACKGROUND: Photodynamic therapy (PDT) has become one of the most effective therapies for the treatment of actinic keratosis, allowing the removal of more than one lesion in a single session. However, the pain sustained by the patient during treatment and local skin reactions can limit its use. OBJECTIVES: To determine the efficacy and safety of combined PDT (daylight PDT followed by conventional PDT) vs conventional PDT 12 weeks after treatment. METHODS: The study was performed as a randomized, single-center, non-inferiority clinical trial with two parallel groups. A total of 51 patients with grade I and II AKs on the scalp or face were randomized. Twenty-five patients received one session of combined PDT (combPDT), and 26 patients received one session of conventional PDT (cPDT). The primary endpoint was the reduction of AKs, 12 weeks after treatment. The secondary endpoint was the reduction in pain and local skin reaction. RESULTS: The reduction rate of grade I and II AKs was similar in combPDT and cPDT, showing no statistically significant differences between both groups, 76.67% vs 86.63% [P = .094] and 80.48% vs 83.08% [P = .679], respectively. However, pain was significantly lower in the combPDT group (2.56 vs 5, P < .01), as were local skin reactions. CONCLUSIONS: CombPDT has proven to be as effective as cPDT for the treatment of grade I and II AKs located on the scalp and face. Furthermore, combPDT has been shown to be considerably more tolerable than cPDT, causing only mild local skin reactions.

Live, Genetically Attenuated, Cold-Chain-Free Cholera Vaccine-A Research and Development Journey: Light at the End of a Long Tunnel.

Cholera, a diarrheal disease caused by Vibrio cholerae (V. cholerae) O139 and O1 strains, remains a public health problem. The existing World Health Organization (WHO)-licenced, killed, multiple-dose oral cholera vaccines demand 'cold-chain supply' at 2 °C-8 °C. Therefore, a live, single-dose, cold-chain-free vaccine would relieve significant bottlenecks and costs of cholera vaccination campaigns. Our cholera vaccine development journey started in 2000 at Universiti Sains Malaysia with isolation of the hemA gene from V. cholerae, followed by development of a gene mutant vaccine candidate VCUSM2 against V. cholerae O139 in 2006. In 2010, VCUSM2 reactogenicity was reduced by replacing its two wild-type ctxA gene copies with mutated ctxA to produce strain VCUSM14. Introducing the hemA gene into VCUSM14 created VCUSM14P, a strain with the 5-aminolaevulinic acid (ALA) prototrophic trait and excellent colonisation and immunological properties (100% protection to wild-type challenged rabbits). It was further refined in Asian Institute of Medicine, Science and Technology (AIMST University), with completion of single- and repeated-dose toxicity evaluations in 2019 in Sprague Dawley (SD) rats, followed by development of a novel cold-chain-free VCUSM14P formulation in 2020. VCUSM14P is unique for its intact cholera toxin B, a known mucosal adjuvant. The built-in adjuvant makes VCUSM14P an ideal vaccine delivery platform for emerging diseases (e.g. severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] and tuberculosis). Our vaccine formulation mimics natural infection, remains non-reactogenic and immunogenic in vivo, and protects against infection and disease. It will also cost less and be less cumbersome to distribute due to its stability at room temperature. These features could revolutionise the outreach of this and other vaccines to meet global immunisation programmes, particularly in low-resourced areas. The next stage of our journey will be meeting the requisite regulatory requirements to produce the vaccine for rollout to countries where it is most needed.

Treatment of superficial basal cell carcinoma with 7.8% 5-aminolaevulinic acid nanoemulsion-based gel (BF-200 ALA) and photodynamic therapy: Results in clinical practice in a tertiary hospital.

Photodynamic therapy (PDT) is an effective treatment option for the treatment of superficial basal cell carcinoma (sBCC). Recent publications have demonstrated that PDT with 7.8% 5-aminolaevulinic acid nanoemulsion-based gel (BF-200 ALA-PDT) is an effective and safe alternative for the treatment of sBCC). To investigate the efficacy and safety of 7.8% 5-aminolaevulinic acid nanoemulsion-based gel (BF-200 ALA)-PDT for the treatment of sBCC. A non-controlled, open-label single centre study was conducted. Patients received one PDT cycle with two PDT sessions one-week apart. In case that clinical-dermoscopy evaluation of treatment outcome revealed remaining lesions, a second PDT cycle was performed. The clinical results at the dermoscopy and fluorescence diagnosis level were histologically confirmed in all patients. Treatment response was evaluated 3, 6, and 12 months after last PDT session. A total of 31 patients (12 men and 19 women), with a median age of 63.74 years were included in this study. 3-month after PDT-session, 23/31 patients were complete responders (74.19%) after two BF-200 ALA -PDT sessions. Esthetic outcome was considered good-to-excellent. 5 Aminolevulinic acid 7.8% nanoemulsion-based gel (BF-200 ALA) PDT is an effective therapy option for the treatment of sBCC. Complete clearance rates were higher in those patients who received only one PDT cycle. These results show a similar tendency as shown in other publications.

5-aminolaevulinic acid-based photodynamic therapy induces both necrosis and apoptosis of keratinocytes in plantar warts.

BACKGROUND: 5-aminolaevulinic acid (ALA)-based photodynamic therapy (ALA-PDT) is an effective treatment for proliferative skin diseases. Many studies revealed that ALA-PDT induces apoptosis of cancer cells. However, the mechanism of PDT in warts is not fully elucidated. OBJECTIVE: This study was designed to explore the efficacy of ALA-PDT for plantar warts and its possible mechanism. METHODS: Twenty-five patients with plantar warts underwent four rounds of ALA-PDT at weekly intervals. Therapeutic effects were observed 1 month since last treatment. The adverse reactions were also recorded during and after the procedure. To observe histological changes, 5 patients accepted tissue biopsies before and 24 h after first PDT treatment. RESULTS: Twenty-two patients (88%) showed a complete response. Twenty patients complained of a mild burning sensation during treatment, and four patients developed local edema immediately after red light exposure. Five patients had burns after treatment, which disappeared within 24 h. Histologically, epidermal keratinocytes demonstrated remarkable necrocytosis and apoptosis after PDT. CONCLUSIONS: ALA-PDT is highly effective for treatment of plantar warts. The most common adverse effects observed in patients are pain and edema. ALA-PDT might eradicate plantar warts by activating both necrosis and apoptosis to trigger the death of proliferating keratinocytes.

5-aminolaevulinic acid (ALA), enhances heme oxygenase (HO)-1 expression and attenuates tubulointerstitial fibrosis and renal apoptosis in chronic cyclosporine nephropathy.

BACKGROUND: Cyclosporine-A (CsA) is an immunosuppressant indicated for various immunological diseases; however, it can induce chronic kidney injury. Oxidative stress and apoptosis play a crucial role in CsA-induced nephrotoxicity. The present study evaluated the protective effect of combining 5-aminolaevulinic acid with iron (5-ALA/SFC), a precursor of heme synthesis, to enhance HO-1 activity against CsA-induced chronic nephrotoxicity. METHODS: Mice were divided into three groups: the control group (using olive oil as a vehicle), CsA-only group, and CsA+5-ALA/SFC group. After 28 days, the mice were sacrificed, and blood and kidney samples were collected. In addition to histological and biochemical examination, the mRNA expression of proinflammatory and profibrotic cytokines was assessed. RESULTS: Renal function in the 5-ALA/SFC treatment group as assessed by the serum creatinine and serum urea nitrogen levels was superior to that of the CsA-only treatment group, demonstrating that 5-ALA/SFC significantly attenuated CsA-induced kidney tissue inflammation, fibrosis, apoptosis, and tubular atrophy, as well as reducing the mRNA level of TNF-α, IL-6, TGF-ß1, and iNOS while increasing HO-1. CONCLUSION: The activity of 5-ALA/SFC has important implications for clarifying the mechanism of HO-1 activity in CsA-induced nephrotoxicity and may provide a favorable basis for clinical therapy.

Effect of light polarization on the efficiency of photodynamic therapy of basal cell carcinomas: an in vitro cellular study.

In an in vitro study, the effect of light polarization on the efficiency of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) of basal cell carcinoma (BCC) was investigated. Three states of light polarization (non-polarized, linearly polarized, and circularly polarized) were considered. Cells were exposed to green (532 pm 20 nm) irradiation from light emitting diodes. Cell survival was measured by the colorimetric assay (WST-1) and Trypan blue staining. The colorimetric assay showed a pronounced decrease in the cell viability (up to 30%) using polarized light compared to the non-polarized one in the wavelength region used. Similar results were obtained by the cell counting method (20-30% increase in cell death). The observed effect was dependent on the concentration of photosensitizer. The effect is more expressed in the case of linearly polarized light compared to the circularly polarized one. Results show that the use of polarized light increases the efficiency of in vitro ALA-PDT of BCC. Utilizing polarized light, it is possible to obtain the same effect from PDT by lower concentrations of photosensitizer. Additionally, the concentration dependency of PDT response and photo-bleaching is also reduced.

5-aminolaevulinic acid patch-photodynamic therapy in the treatment of actinic cheilitis.

BACKGROUND: Actinic cheilitis (AC) is a common disease caused by chronic ultraviolet exposure. OBJECTIVE: Alacare is a self-adhesive, skin coloured 5-aminolaevulinic acid (ALA) patch that has been developed for the treatment of mild to moderate actinic keratosis (AK). Considering the good results in the treatment of AK, the standardized delivery of ALA and the simple application Alacare patch- photodynamic therapy (PDT) appears as an interesting treatment option for AC. METHODS: We retrospectively assessed the efficacy, tolerability and cosmetic outcome of Alacare patch-PDT in eleven patients with AC. After occlusion with the Alacare patches for 4 hours, the AC lesions were illuminated with narrowband red light and a dose of 37 J/cm2 . All patients were clinically assessed for efficacy, side effects and cosmetic outcome at 3, 6, 9 and 12 months after treatment. RESULTS: Complete clinical response at the 3-month follow-up was achieved in eight of 11 patients (72,7%) and 12 of 15 AC lesions (80,0%), respectively. Up to the final 12-month follow-up, a recurrence was observed in two lesions. The complete clinical cure rate at 1 year after Alacare patch-PDT, thus, was 66,6% (10/15 lesions). The cosmetic outcome of the treatment was excellent in all cases. CONCLUSION: Alacare patch-PDT was found to have substantial efficacy in the treatment of mild to moderate AC. Given its ease of use, absence of long-term side effects and the excellent cosmetic results Alacare patch-PDT might be considered as a promising new treatment option for the management of AC.

Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents.

5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy.

5-aminolevulinic acid induced photodynamic reactions in diagnosis and therapy for female lower genital tract diseases.

Since the patients suffering from female lower genital tract diseases are getting younger and younger and the human papilloma virus (HPV) infection is becoming more widespread, the novel non-invasive precise modalities of diagnosis and therapy are required to remain structures of the organ and tissue, and fertility as well, by which the less damage to normal tissue and fewer adverse effects are able to be achieved. In all nucleated mammalian cells, 5-Aminolevulinic acid (5-ALA) is an amino acid that occurs spontaneously, which further synthesizes in the heme biosynthetic pathway into protoporphyrin IX (PpIX) as a porphyrin precursor and photosensitizing agent. Exogenous 5-ALA avoids the rate-limiting step in the process, causing PpIX buildup in tumor tissues. This tumor-selective PpIX distribution after 5-ALA application has been used successfully for tumor photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Several ALA-based drugs have been used for ALA-PDD and ALA-PDT in treating many (pre)cancerous diseases, including the female lower genital tract diseases, yet the ALA-induced fluorescent theranostics is needed to be explored further. In this paper, we are going to review the studies of the mechanisms and applications mainly on ALA-mediated photodynamic reactions and its effectiveness in treating female lower genital tract diseases.

Effect of topical 5-aminolevulinic acid photodynamic therapy versus therapy combined with CO2 laser pretreatment for patients with cervical high-grade squamous intraepithelial lesions.

OBJECTIVE: To evaluate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with CO2 laser pretreatment (Laser+ALA-PDT) on patients with cervical high-grade squamous intraepithelial lesions (HSILs). METHODS: A total of 114 patients treated by ALA-PDT or Laser+ALA-PDT at 3 centers were retrospectively reviewed. The effective rate, cure rate of lesions as well as high-risk human papillomavirus (HR-HPV) regression rate and persistent infection rate in the 2 groups were compared according to 3-6 month and 9-12 months follow-ups. The characteristics and risk factors for ineffective cases were evaluated by regression analysis. RESULTS: At the 3-6month follow-up, the effective rate was significantly higher in the Laser+ALA-PDT group than in the ALA-PDT group (96.6% vs. 81.3%, p = 0.048). A total of 79.3% of the laser+ALA-PDT patients achieved cure rate compared with 61.3% of the ALA-PDT patients (p = 0.082). In the Laser+ALA-PDT group, the HR-HPV-negative rate was significantly higher (72.4% vs. 50.7%, p = 0.045), while the persistence rate was significantly lower (20.7% vs. 42.7%, p = 0.037). At the 9-12month follow-up, the cure rate was 83% in the ALA-PDT group, 17% lower than that in the Laser+ALA-PDT group (p = 0.055). A total of 20.8% of patients in the ALA-PDT group and 5.3% in the Laser+ALA-PDT group showed persistent HR-HPV infection (p = 0.120). Pretreatment HR-HPV type, multiple infections and treatment modality were relevant factors for PDT outcome. CONCLUSIONS: For patients with cervical HSIL, laser+ALA-PDT shows better efficiency and HPV regression compared with ALA-PDT. HPV16/18 and multi-infection may be risk factors for ineffective treatment with ALA-PDT.

Case report: Acne vulgaris treatment with 5-Aminolaevulinic acid photodynamic therapy and adalimumab: a novel approach.

Acne vulgaris is a common skin condition that affects a large proportion of teenagers and young adults. Despite the availability of various treatment options, many patients experience inadequate relief or intolerable side effects. Photodynamic therapy (PDT) is a growing interest in the treatment of acne vulgaris, with 5-Aminolaevulinic acid (ALA) being one of the most commonly used photosensitizers. Adalimumab is a biologic medication used to treat inflammatory skin conditions such as Psoriasis and Hidradenitis suppurativa (HS), which targets TNF-α. Combining different therapies, such as ALA-PDT and adalimumab, can often provide more effective and longer-lasting results. This report presents the case of a patient with severe and refractory acne vulgaris who was treated with a combination of ALA-PDT and adalimumab, resulting in significant improvement in the condition. The literature review highlights the significant comorbidity associated with acne, emphasizing the need for potential of TNF-α inhibitors for its effective treatments that address physical symptoms and ALA-PDT is known to treat scar hyperplasia, and to prevent or minimize the formation of post-acne hypertrophic scars. The combination of TNF inhibitors and ALA-PDT or adalimumab has shown promising results in treating inflammatory skin conditions, including severe and refractory acne vulgaris, as per recent studies.

The response of the canine mammary simple carcinoma and carcinosarcoma cells to 5-aminolaevulinic acid-based photodynamic therapy: An in vitro study.

BACKGROUNDS: Canine mammary gland tumors (CMGTs) are heterogeneous tumors and share many similar features with human breast cancer. Despite the improvement of current treatment options, new treatment modalities are required to effectively kill tumor cells without general toxicity in the treatment of CMGTs. Photodynamic therapy (PDT) is a promising method for cancer treatment. However, there is a limited study evaluating the therapeutic efficacy of PDT in the treatment of CMGTs. METHODS: In this context, we, for the first time, investigated the therapeutic potential of 5-aminolaevulinic acid (5-ALA) mediated PDT at 6 and 12 J/cm2 in two different subtypes [Tubulopapillary carcinoma (TPC) and carcinosarcoma (CS)] cells via different molecular analysis. The cytotoxic effects of 5-ALA/PDT on these cells were analyzed by intracellular PpIX level, WST-1 and ROS analysis. Furthermore, the underlying moleculer mechanism of 5-ALA/PDT mediated apoptotic effects on TPC and CS cells were evaluated Annexin V, AO/PI, RT-PCR and western blot analysis. RESULTS: The 5-ALA/PDT treatment upon irradiation considerably inhibited the viability of both TPC and CS cells (p<0.01) and caused apoptotic death through elevated ROS levels, the activation of Caspase-9, and Caspase-3, and the overexpression of Bax. However, the response of TPC and CS cells to 5-ALA/PDT was different. CONCLUSIONS: Our preliminary in vitro findings provide novel insights into the molecular mechanisms underlying 5-ALA/PDT mediated apoptosis in both TPC and CS cells. However, the therapeutic response of CMGT cells to 5-ALA/PDT is limited.

Effectiveness of photodynamic therapy with 5-aminolevulinic acid on HPV clearance in women without cervical lesions.

BACKGROUND: High-risk HPV (hrHPV) not only increases the risk of cervical precancerous lesions and cervical cancer, but also adds psychological burden to HPV-positive women. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive and highly tissue-selective therapy. We aim to investigate the clinical efficacy of ALA-PDT for elimination of cervical hrHPV infection in HPV-positive women without cervical lesions. METHODS: A total of 57 hrHPV-positive women without pathologically proved cervical lesions received three treatments of ALA-PDT in total. HPV DNA testing and pap cytology were performed in all patients. Patients with positive HPV16/18 or abnormal TCT results received colposcopic biopsy during the follow-up. RESULTS: hrHPV clearance rate was 56.1 % (32/57) at 3-month follow-up and 68.1 % at 6-month follow-up. 100 % of HPV 18 and 87.5 % of HPV16 infections were cleared while the clearance rate was 48.8 % among those positive for 12 other high-risk types. Multivariate analysis showed HPV16/18 infection was associated with significantly higher clearance rate. HPV clearance rate in patients with multiple-type HPV infection was significantly lower than that in patients with single-type HPV infections. CONCLUSIONS: ALA-PDT is effective on treating hrHPV infection in patients with no cervical lesions. HPV16/18 positive cases can benefit most from ALA-PDT. Multitype-infected women need more sessions of 5- ALA-PDT to eradicate hrHPV infection.

Novel Visualization Methods Assisted Transurethral Resection for Bladder Cancer: An Updated Survival-Based Systematic Review and Meta-Analysis.

BACKGROUND: Photodynamic diagnosis and narrow-band imaging could help improve the detection rate in transurethral resection (TUR) of bladder cancer. It remained controversial that the novel visualization method assisted transurethral resection (VA-TUR) could elongate patients' survival compared to traditional TUR. METHODS: We performed electronic and manual searching until December 2020 to identify randomized controlled trials comparing VA-TUR with traditional TUR, which reported patients' survival data. Two reviewers independently selected eligible studies, extracted data, assessed the risk of bias. Meta-analysis was conducted according to subgroups of types of visualization methods (A) and clinical stage of participants. Publication bias was detected. RESULTS: We included 20 studies (reported in 28 articles) in this review. A total of 6,062 participants were randomized, and 5,217 participants were included in the analysis. Only two studies were assessed at low risk of bias. VA-TURB could significantly improve the recurrence-free survival (RFS) (HR = 0.72, 95% CI: 0.66 to 0.79, P <0.00001, I2 = 42%) and progression-free survival (PFS) (HR = 0.62, 95% CI: 0.46 to 0.82, P <0.0008, I2 = 0%) compared with TUR under white light. The results remain stable whatever the type of visualization method. The difference could be observed in the non-muscle-invasive bladder cancer (NMIBC) population (P <0.05) but not in the mixed population with muscle-invasive bladder cancer (MIBC) participants (P >0.05). CONCLUSION: VA-TUR could improve RFS and PFS in NMIBC patients. No significant difference is found among different types of VA-TUR. VA-TUR may be not indicated to MIBC patients.

Effectiveness of photodynamic therapy in women of reproductive age with cervical high-grade squamous intraepithelial lesions (HSIL/CIN2).

OBJECTIVE: To evaluate the histologic response rate of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia 2 (CIN2) of the cervix after photodynamic therapy (PDT) treatment in women with fertility requirements. MATERIALS AND METHODS: A retrospective study was carried out comprising 31 female patients aged 20-38 years with histologically confirmed HSIL/CIN2 with high-risk human papillomavirus (hrHPV) infection. Patients were treated with three sessions of 20% 5-aminolevulinic acid (5-ALA) PDT at intervals of 7-14 days. All patients had a follow-up including cytology, HPV testing and colposcopy-directed biopsy after PDT treatment at the 6-month and 12-month follow-up points. The main outcome measure was efficacy, defined as complete histologic remission 12 months after PDT. Secondary outcomes were the remission of HPV infection and the adverse effects of PDT treatment. RESULTS: At the 12-month follow-up, 21 out of 27 patients (77.78%) and 4 out of 27 patients (14.81%) showed histologic disappearance and histologic regression, respectively. Only 7.41% (2/27) patients persisted with HSIL/CIN2. In addition, no patients progressed to CIN3 or carcinoma. The total baseline HPV remission rate was 62.96% (17/27). The remission rate of HPV16/18 was statistically significant compared to the other hrHPV (57.14% vs. 100%, p = 0.016) in the group with HISL/CIN2 disappearance. Adverse events were mild, with increased vaginal secretion and abdominal pain being the most common complaints. There was no report of adverse events such as vaginal bleeding, colporrhagia, ulcer, or abdominal pain after PDT treatment. CONCLUSIONS: 5-ALA-PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with HSIL/CIN2 who have fertility requirements.

The effect of 5-Aminolaevulinic Acid Photodynamic Therapy versus CO2 laser in the Treatment of Cervical Low-grade Squamous Intraepithelial Lesions with High-Risk HPV Infection: A non-randomized, controlled pilot study.

BACKGROUND: There are insufficient studies comparing the efficacy of 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) against CO2 laser therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with high-risk human papillomavirus (HR-HPV), especially for long-term efficacy. METHODS: Patients with cervical LSIL and HR-HPV infection were divided into two treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4-6 months and 12 months after the treatment. RESULTS: (1) Among 277 patients, 176 patients received 5-ALA PDT and 101 patients received CO2 laser therapy. (2) 4-6 months after treatment, there was no significant difference between two groups in the complete remission (CR) rates of cervical LSIL and the clearance rate of HR-HPV infection. (3) 12 months after treatment, compared with the CO2 laser group, the CR rates of cervical LSIL in the 5-ALA PDT group was significantly higher than the CO2 laser group. There was no statistical difference in the clearance rate of HR-HPV infection between the two groups. (4) 12 months after treatment, the recurrence rate of cervical lesions and the reinfection rate of HR-HPV infection in 5-ALA PDT group were significantly lower than those in CO2 laser group. CONCLUSION: The effect of 5-ALA PDT is similar to CO2 laser at 4-6 months. The long-term efficacy of 5-ALA PDT appears better than CO2 laser. As a non-invasive treatment, 5-ALA PDT is a highly effective therapeutic procedure for cervical LSIL with HR-HPV infection.

Performance of Narrow Band Imaging (NBI) and Photodynamic Diagnosis (PDD) Fluorescence Imaging Compared to White Light Cystoscopy (WLC) in Detecting Non-Muscle Invasive Bladder Cancer: A Systematic Review and Lesion-Level Diagnostic Meta-Analysis.

Despite early detection and regular surveillance of non-muscle invasive bladder cancer (NMIBC), recurrence and progression rates remain exceedingly high for this highly prevalent malignancy. Limited visualization of malignant lesions with standard cystoscopy and associated false-negative biopsy rates have been the driving force for investigating alternative and adjunctive technologies for improved cystoscopy. The aim of our systematic review and meta-analysis was to compare the sensitivity, specificity, and oncologic outcomes of photodynamic diagnosis (PDD) fluorescence, narrow band imaging (NBI), and conventional white light cystoscopy (WLC) in detecting NMIBC. Out of 1,087 studies reviewed, 17 prospective non-randomized and randomized controlled trials met inclusion criteria for the study. We demonstrated that tumor resection with either PDD and NBI exhibited lower recurrence rates and greater diagnostic sensitivity compared to WLC alone. NBI demonstrated superior disease sensitivity and specificity as compared to WLC and an overall greater hierarchical summary receiver operative characteristic. Our findings are consistent with emerging guidelines and underscore the value of integrating these enhanced technologies as a part of the standard care for patients with suspected or confirmed NMIBC.

Photodynamic detection of a feline meningioma using 5-aminolaevulinic acid hydrochloride.

CASE SUMMARY: The present study describes the case of a feline meningioma that was detected using 5-aminolaevulinic acid hydrochloride (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence at surgery. An extra-axial mass in the temporoparietal region was observed by MRI. Following craniectomy and durotomy, photodynamic detection (PDD) was performed for detection of the tumour. Intratumour PpIX was detected using fluorescence spectrum evaluation and high-performance liquid chromatography. PDD revealed bright fluorescence of PpIX induced by 5-ALA, facilitating fluorescence-guided resection of the tumour tissue. Postoperative examination demonstrated an intratumour PpIX protein concentration of 16.8 nmol/g, and based on histopathological findings we diagnosed the mass as meningioma. RELEVANCE AND NOVEL INFORMATION: PDD using 5-ALA has been used to identify the surgical margins during resection of primary human brain tumours. Recently, we have reported post-mortem PDD using 5-ALA for a canine glioblastoma. To our knowledge, this technique has not been previously used for the detection and resection of feline brain tumours. Our findings suggest that PDD using 5-ALA is useful for intraoperative fluorescence-guided resection of malignant meningioma in cats.

Efficacy of 5-aminolevulinic acid and LED photodynamic therapy in cervical intraepithelial neoplasia: A clinical trial.

BACKGROUND: 5-Aminolaevulinic acid (5ALA) is a precursor of the strong sensitizer protoporphyrin IX (PpIX) in the heme synthesis pathway. We conducted aclinical trial designed to evaluate the efficacy and safety of 5ALA photodynamic therapy (PDT) using a light-emitting diode (LED) in patients with cervical intraepithelial neoplasia (CIN). METHODS: Data for 51 CIN patients who underwent 5ALA-PDT between 2012 and 2017 were prospectively analysed. After a 20 % 5ALA jelly formulation was topically applied to the cervix, the region was irradiated with red light at approximately 633 nm to excite PpIX for treatment. We estimated outcomes by cytology, pathology, and human papilloma virus (HPV) testing after PDT. RESULTS: Patients underwent two PDT sessions at one-week intervals during outpatient treatment and achieved favourable results without photosensitivity and severe adverse events. Over a long follow-up period, 96.1 % of all patients showed some positive effects, including approximately 70 % with a complete response (CR), 10 % with a partial response, and 15 % with downgrades. The HPV clearance rate in patients with CR was 79.4 %. Recurrence occurred in five patients who mostly remained HPV-positive after PDT. CONCLUSIONS: Based on our study, topical 5ALA-PDT using an LED light source potentially represents a safe treatment for CIN on an outpatient basis.