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Aim: The aim of our study was to explore the factors influencing cerebral edema and intracranial pressure in glioblastoma multiforme (GBM) patients who undergo photodynamic therapy (PDT) after resection., Approach: This was a retrospective controlled study of GBM patients treated with PDT-assisted resections of varying scope from May 2021 to August 2023. The baseline clinical data, cerebral edema volumes, intracranial pressure values, and imaging data of the GBM patients were collected for statistical analysis., Results: A total of 56 GBM patients were included. Thirty of the patients underwent gross total resection (GTR), and the other 26 patients underwent subtotal resection (STR). We found that the cerebral edema volume and the mean intracranial pressure in patients who underwent GTR were lower than those in patients who underwent STR. Moreover, univariate analysis showed that the scope of tumor resection was an independent factor affecting cerebral edema and intracranial pressure after PDT., Conclusions: Compared with STR, PDT combined with GTR significantly reduced postoperative brain edema volume and intracranial pressure in GBM patients., (© 2024 Wiley Periodicals LLC.)

Background: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution., Methods: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale., Results: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination., Conclusions: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT., (© 2024 Wiley Periodicals LLC.)

Background: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades., Aim: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities., Method: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C 0 ), with data weighted by cohort size, was used to evaluate the final efficacy for each modality., Result: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C 0 , 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C 0 , 0.54 vs. 0.46, p = 0.714), and young children (C 0 , 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults., Conclusion: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children., (© 2024 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

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.)

Elsinochrome A (EA) is a perylene quinone natural photosensitizer, photosensitizer under light excitation generates reactive oxygen species (ROS) to induce apoptosis, so can be used for treating tumors, that is so-called photodynamic therapy (PDT). However, the molecular mechanism, especially related to apoptosis and autophagy, is still unclear. In this study, we aimed to explore the mechanism of EA-PDT-induced B16 cells apoptosis and autophagy. The action of EA-PDT on mitochondrial permeability transition pore (MPTP), mitochondrial membrane potential (MMP) and the mitochondrial function were researched by fluorescence technique and Extracellular Flux Analyzer. Illumina sequencing, tandem mass tags Quantitative Proteomics and Western Blot studied the mechanism at the gene and protein levels. The results indicated that EA-PDT had excellent phototoxicity in vitro. EA could bind to the mitochondria. EA-PDT for 5 min caused MPTP opening, MMP decreasing and abnormal mitochondrial function with a concentration-dependent characteristic. EA-PDT resulted in an increase intracellular ROS and the number of autophagosomes. Caspase2, caspase9 and tnf were upregulated, and bcl2, prkn, atg2, atg9 and atg10 were downregulated. Our results indicated that EA-PDT induced cell apoptosis and autophagy through the mediation of ROS/Atg/Parkin. This study can provide enlightenment for exploring potential targets of drug development for the PDT of melanoma., (© 2023 Wiley Periodicals LLC.)

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current treatments but lectin-based therapy targeting cell surface glycans could be a promising new horizon. Here, we report a novel lectin-based phototherapy (Lec-PT) that combines the PDAC targeting ability of rBC2LCN lectin to a photoabsorber, IRDye700DX (rBC2-IR700), resulting in a novel and highly specific near-infrared, light-activated, anti-PDAC therapy. Lec-PT cytotoxicity was first verified in vitro with a human PDAC cell line, Capan-1, indicating that rBC2-IR700 is only cytotoxic upon cellular binding and exposure to near-infrared light. The therapeutic efficacy of Lec-PT was subsequently verified in vivo using cell lines and patient-derived, subcutaneous xenografting into nude mice. Significant accumulation of rBC2-IR700 occurs as early as 2 hours postintravenous administration while cytotoxicity is only achieved upon exposure to near-infrared light. Repeated treatments further slowed tumor growth. Lec-PT was also assessed for off-target toxicity in the orthotopic xenograft model. Shielding of intraperitoneal organs from near-infrared light minimized off-target toxicity. Using readily available components, Lec-PT specifically targeted pancreatic cancer with high reproducibility and on-target, inducible toxicity. Rapid clinical development of this method is promising as a new modality for treatment of pancreatic cancer., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background and Objectives: Conventional ALA-PDT (C-PDT) has limited efficacy in cutaneous squamous cell carcinoma (cSCC), and there is obvious pain during treatment, which limits its clinical application. We sought to modify photodynamic therapy into a more painless and effective treatment., Methods: We modified C-PDT by reducing the incubation time of the pro-sensitizer and increasing the light dose; we named this method modified ALA-PDT (M-PDT). We compared the pain response and curative effect between C-PDT and M-PDT in cSCC mouse models. Pain-related proteins were examined by western blot analysis and immunohistochemistry. Tumor progression-associated signaling pathways were analyzed by RNA-seq and western blot analysis. Reactive oxygen species (ROS) generation was measured with a ROS test kit and Microplate reader., Results: M-PDT greatly reduced pain during treatment. Interestingly, when the cSCC tumor volume increased to 150-200 mm 3 , M-PDT almost completely eliminated the tumors, while C-PDT did not. The better curative effect of M-PDT might be due to the stronger suppression of the Stat3, Erk1/2, and mTOR signaling pathways. Moreover, flow cytometry demonstrated that M-PDT could recruit CD8 + T cells to inhibit cSCC progression. Further investigation determined that the different mechanisms of C-PDT and M-PDT were related to more ROS generation induced by M-PDT., Conclusions: Our results suggest that M-PDT, which is more painless and effective than C-PDT, is expected to provide a solution for the treatment of cSCC., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: Photodynamic therapy (PDT) is a cancer treatment modality mediated by reactive oxygen species (ROS). However, the intracellular antioxidant defense system antagonizes PDT-generated ROS, impeding PDT efficacy. This study aimed to evaluate the enhancement of PDT cytotoxicity by its combination with natural antioxidants in pro-oxidant concentrations., Methods: A rich natural antioxidant mixture originating from Pinus halepensis bark extract was studied for its potential to enhance the efficacy of m-tetrahydroxyphenylchlorin (m-THPC)-PDT on LNCaP prostate cancer cells, in vitro. Various P. halepensis concentrations, at two different incubation times, were used in combination with m-THPC-PDT. Assessment of cellular viability and intracellular ROS levels evaluated the treatments' outcome. A novel method was developed for the assessment of the intracellular ROS levels, based on image analysis and data extraction from fluorescence microscopy images., Results: P. halepensis bark extract increased the intracellular ROS levels in a concentration-dependent but not in an incubation-dependent manner. The higher concentrations used (≥50 μg/ml) reduced cellular viability even by 50%. One hour pretreatment with 30 μg/ml P. halepensis before m-THPC-PDT exceeded the levels of cellular death by approximately 15%., Conclusions: The results provided evidence of the cytotoxic effect of P. halepensis bark extract on LNCaP cells, showing the potential of P. halepensis to be used as an anticancer agent in prostate cancer treatment. The results also provided evidence of enhancement of m-THPC-PDT by P. halepensis bark extract showed the potential to be used as a supplementary agent to improve prostate cancer PDT treatment., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: Control of burn wound infection is difficult due to the increase in drug-resistant bacteria and deteriorated immune responses. In this study, we examined the usefulness of methylene blue (MB)-mediated antimicrobial photodynamic therapy (aPDT) with illumination by a light-emitting diode (LED) array for controlling invasive infections from the wound to inside the body for rats with an extended deep burn infected with Pseudomonas aeruginosa., Study Design/materials and Methods: An MB solution with the addition of ethanol, ethylene-diamine-tetra-acetic acid disodium salt, and dimethyl sulfoxide was used as a photosensitizer (PS). An extended deep burn was made on the dorsal skin in rats and the wounds were infected with P. aeruginosa. The rats were divided into three groups: control (no treatment; n = 14), PS mixture application alone (PS alone group; n = 10), and aPDT group (n = 14). For aPDT, after the PS mixture was applied onto the surface of infected wounds, the wounds were illuminated with a 665-nm LED array at an intensity of 45 mW/cm 2 three times per treatment, with an illumination duration of 20 minutes and an interval of 10 minutes. The treatment was repeated each day for 7 consecutive days (day 0-day 6). Bacterial numbers on the wound surface and the weights and survival rates of the animals were evaluated daily. At the endpoints, bacterial numbers in the liver and blood were counted. Since the PS mixture showed high dark toxicity against P. aeruginosa in vitro, the influence of the PS mixture application onto healthy skin was also examined in vivo., Results: Even in the aPDT group, rapid bacterial regrowth was observed on the wound surface after each day's treatment, but the geometric mean values of the bacterial numbers before and after each aPDT were considerably lower than those in the control group. Application of the PS mixture alone showed a clear bactericidal effect only at day 0, which is attributable to the formation of biofilms after day 1. Rats in the aPDT group showed a smaller weight loss, a higher ratio of no bacterial migration at the endpoints, and significantly higher survival rates than those in the other two groups. Effects of repeated application of the PS mixture onto healthy skin were not evident., Conclusions: Application of MB-mediated aPDT with illumination by a high-intensity LED array daily for seven consecutive days was effective for suppressing invasive infection from the wound to inside the body in rats with an extensive deep burn infected with P. aeruginosa, resulting in significant improvement of their survival. Lasers Surg. Med. © 2021 Wiley Periodicals LLC., (© 2021 Wiley Periodicals LLC.)

Background and Objectives: Photodynamic therapy (PDT) has gained widespread popularity in the last decades because of its distinctive advantages over the other commonly used cancer treatments. PDT dosimetry is a crucial factor in achieving a good optimization of PDT treatment planning. PDT dosimetry is a complex task since light dose as well as photosensitizer and oxygen concentrations in tissue need to be measured (ideally continuously) to be able to fully characterize the biological response. Light dose in PDT is routinely measured by the optical fibers that provide dose data at a limited number of discrete points and are not able to capture spatial dose profiles. The objective of this study is to propose and develop a new optical method for online monitoring of the dose profile data for PDT., Study Design/materials and Methods: Using the digital holography technique, first, the general sketch of an experimental setup for PDT light dosimetry is provided. The theory behind the proposed method for using the experimental setup in PDT light dosimetry is fully described, and its limits of validity are determined. In a proof of principle study, the ability of the method for online monitoring of the absorbed light dose profile in PDT is evaluated by a simple experimental setup., Results: The experimental results confirm the usefulness of the proposed method in providing continuous online dose profiles. The absorbed light dose profiles from an infrared light source in a quartz cell containing water are measured and shown. The depth-dose curves are extracted and it is shown that how these dosimetric data can be used for assisting the physicians in determining the appropriate spatiotemporal characteristics for treating the infected tissues and solid tumors with the required light dose amounts. A conversion relation is also derived for transforming the measured light dose with the proposed method to the most frequently used dose values by PDT practitioners, in terms of light power per square area., Conclusions: There is no restriction in using the method with other commonly used light sources in PDT, like light-emitting diodes and filtered lamps, with different wavelengths in visible or infrared regions of the spectrum. More complex experimental setups can be used in future studies to study the role of accumulated photosensitizers in malignant tissues. The proposed method in this study can also be used for light dose monitoring in other biomedical applications, where light is used for treating special diseases, and patients must receive sufficient amounts of light dose. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Background and Objective: Vulvar 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 Methods: Seventeen 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., Results: A 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., Conclusion: Combined 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., (© 2019 Wiley Periodicals, Inc.)

Photosensitizers (PSs) are ideal cancer theranostic drugs that can be administered as both fluorescence imaging reagents and photodynamic therapy (PDT) drugs. To improve the tumoritropic behavior of PSs, nanoliposomes are presently being considered as optimal PSs carriers. Although nanoliposomal PSs have been utilized in clinical therapy, PSs localization and photosensitive processing in nanoliposomal PSs are rarely observed on nanoscale. Investigating changes in the fine structure of nanoliposomes under photosensitive processing will further our understanding of the photosensitive effect on nanoliposomal PSs. In this study, nanoliposomes co-encapsulating the PSs benzoporphyrin derivative monoacid A (BPD) and the photoswitchable probe Cy5-927 were prepared to realize PDT and nanoscale super-resolution optical imaging. The fine structures of nanoliposomal BPD and Cy5-927 (LBC) were visualized by a home-built stochastic optical reconstruction microscopy (STORM). Our PDT results showed that the photorelease and PDT efficiency of BPD were not decreased by co-encapsulating with Cy5-927 in LBC. Taken together, LBC can be used as a new optical probe and PDT reagent for investigating changes in nanoliposomes fine structure and micro-interaction in the cellular process of PDT. Therefore, our results deepened our understanding of liposome-based PDT for optimizing cancer treatment. © 2019 International Society for Advancement of Cytometry., (© 2019 International Society for Advancement of Cytometry.)

Background and Objectives: Décolleté photodamage is a common condition typically treated with light and energy-based devices. This study investigated the efficacy and safety of a fractional 1,927 nm thulium laser (TL) alone and combined with photodynamic therapy (PDT)., Study Design/materials and Methods: In a 12-week follow-up study, participant décolletés were divided into four treatment areas and randomized to receive a single treatment with field-directed TL, PDT, combination TL-PDT, or lesion-directed curettage control. All actinic keratoses (AKs) underwent lesion-directed curettage before randomization. TL was delivered at 20 mJ/mb, 500 mJ/cm 2 fluence, 5 W, and 8 (n = 6 pts.) or 16 (n = 6 pts.) passes. PDT was performed with 16% methyl aminolevulinate (MAL) creme incubated for 3 h, followed by red light-emitting diode light at 37 J/cm 2 . Outcome measures included clinical assessment of overall photodamage and specific subcomponents, assisted by optical coherence tomography (OCT) imaging., Results: Twelve women with moderate to severe photodamage on the décolleté and a cumulative total of 184 thin grade I AKs were included. Field-directed treatments TL and combination TL-PDT equally improved the overall photodamage, mottled pigmentation, and rhytides compared with lesion-directed control (P < 0.05). The skin texture improved by TL alone and was further improved by combining TL and PDT (P < 0.05). Median AK complete responses were similar for field-directed interventions TL-PDT (100%), TL (90%), PDT (82%), and lesion-directed curettage control (52%) (P = 0.464). Patients presented with mild local skin responses, slightly more pronounced when combining TL with PDT versus individual treatments (P < 0.05). No scarring or adverse events were observed., Conclusions: The 1,927 nm fractional thulium laser is an effective, tolerable, and safe field-directed treatment for décolleté photodamage. Provided alone, TL proved to be as effective as combined TL-PDT for overall photodamage, while a greater improvement in skin texture was achieved using TL and PDT in combination. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Background and Objectives: Treatment of photoaging and intrinsic aging of the chest, with the associated concerns of skin roughness, uneven pigmentation, laxity, atrophy, and telangiectasias, can be problematic because of the potential for worsened esthetic outcomes with existing treatments. This study assessed the efficacy and safety of using nonablative fractional laser therapy (FLT) pretreatment with photodynamic therapy (PDT) versus PDT alone for chest rejuvenation., Study Design/materials and Methods: In a randomized, evaluator-blinded, split-sided study, adult female patients with photodamage to the chest received three treatment courses over an 8-week period with follow-up visits at Weeks 12 and 20. FLT was applied to one side of the chest, randomly assigned at baseline, followed by aminolevulinic acid-based PDT, delivered using a thermal, short incubation, broad area technique, to both sides of the chest. In-person and photographic assessments were conducted using five-point scales to evaluate outcomes including rhytides, pigmentation, skin texture, and telangiectasias., Results: Eleven adults completed the study, of whom 11 had improved scores for rhytides and 10 had improved scores for skin texture at Week 20. There was no significant difference in any efficacy outcome between FLT and PDT and standard PDT alone. The severity of adverse events was rated significantly greater with the combined FLT-PDT treatment vs PDT alone., Conclusions: Significant improvements were observed vs baseline for both sides of the chest treated with FLT-PDT or standard PDT following three treatment sessions. No significant difference in efficacy was observed between treatment approaches, although adverse events were more severe on the FLT-pretreated side. This study was not registered as it qualified as a nonsignificant risk study. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc., (© 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.)

Background and Objectives: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture., Study Design/materials and Methods: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist., Results: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds., Conclusions: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Vascular-targeted low-dose photodynamic therapy (L-PDT) was shown to improve chemotherapy distribution in malignant pleural tumors such as malignant pleural mesothelioma (MPM). However, the mechanisms triggered by L-PDT on the tumor vasculature are still debated. In pericyte and endothelial cell co-cultures, we show that pericytes exhibit enhanced sensitivity towards L-PDT compared to endothelial cells, displaying actin stress fibers and cellular contraction via Rho/ROCK kinase signaling myosin light chain and focal adhesion kinase phosphorylation (MLC-P, FAK-P). We then confirm, in two separate MPM models, in mice the phosphorylation of the MLC in pericytes specifically following L-PDT. Furthermore, while L-PDT does not affect tumor vascular density or diameter, we show that it enhances tumor vascular pericyte coverage, leads to a drop in tumor interstitial fluid pressure and enhances the transport of FITC-dextran throughout tumors. In conclusion, L-PDT has the potential to stabilize the tumor vascular bed which improves vascular transport. The mechanism described in the present study may help translate and optimize this approach in patients. Lasers Surg. Med. 51:550-561, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Background: Dissecting cellulitis of the scalp (DCS) is difficult to be treated and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is considered to be a potential treatment for inflammatory skin diseases., Objective: To analyze the efficacy and safety of ALA-PDT on DCS., Materials and Methods: The treatment areas of DCS patients were incubated with freshly prepared 10% ALA for 3 hours. The 633 ± 10 nm light with the intensity of 80-100 mw/cm 2 was used as the irradiation source of ALA-PDT, and the irradiation time was 20-30 minutes. Three sessions were applied at an interval of 10-15 days. According to the reduction of lesions and the improvements of patients' symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded., Results: Seven male DCS patients finished the treatments and assessments. One month after three sessions of treatment, one patient recovered, three patients received significant improvement, and one patients received medium improvement. At the 3-month follow-up, two patients recovered, four patients received significant improvement, and one patients received medium improvement. The patients tolerated well to the therapy without any severe adverse effects., Conclusion: 10% ALA-PDT is effective and safe on male DCS patients. As a localized and less invasive treatment, it provides a preferable choice for DCS patients. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Objectives: Compared to normal cells, malignant cells have a high degree of aerobic glycolysis, also known as the Warburg effect. Therefore, supplementing photodynamic therapy (PDT), an established cancer therapy, with metabolic inhibitors can augment the mitochondrial damage by depleting ATP. To assess the combined impact of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) and PDT on apoptosis and autophagy in human breast cancer cells, and examine the molecular basis., Methods: Calcium-AM/PI double staining was used to evaluate cell viability. Reactive oxygen species (ROS), mitochondria membrane potential (MMP), nuclear morphology, and autophagosomes were measured using specific fluorescent markers. In addition, translocation of the apoptosis inducing factor (AIF) from the mitochondria to nucleus was imaged by confocal laser scanning microscopy, and DNA fragmentation was measured using PI staining and comet assay. PGC-1α expression, oxidative phosphorylation, ATP levels, and autophagy related proteins were detected by qRT-PCR, seahorse bioscience XF P extracellular flux analyzer, and Western blotting, respectively., Results: Compared to with either monotherapy, 2-DG+PDT resulted in significantly higher cytotoxicity in the three breast cancer cell lines (MDA-MB-231, MCF-7, and 4T1), which was consistent with tumor growth regression trends seen in the 4T1 xenograft model. A synergistic augmentation of mitochondrial dysfunction (in terms of ROS generation, MMP loss, and PGC-1α down-regulation) and ATP depletion was seen in cells receiving 2-DG and PDT. In addition, nuclear translocation of AIF and the subsequent DNA damage indicated that the cytotoxic effects were mediated by a caspase-independent mechanism, which was relieved by the ROS scavenger N-acetylcysteine. Autophagy via the AMP-activated protein kinase (AMPK) was also observed following 2-DG+PDT, and reversed upon pre-treatment with the autophagy inhibitor 3-methyladenine., Conclusions: The anti-cancer effects of 2-DG+PDT are mediated by both mitochondria triggered apoptosis and AMPK-mediated autophagy. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: Photodynamic therapy (PDT) using δ-aminolevulinic acid (ALA) photosensitization has shown promise in clinical studies for the treatment of early-stage oral malignancies with fewer potential side effects than traditional therapies. Light delivery to oral lesions can also carried out with limited medical infrastructure suggesting the potential for implementation of PDT in global health settings., Objectives: We sought to develop a cost-effective, battery-powered, fiber-coupled PDT system suitable for intraoral light delivery enabled by smartphone interface and embedded electronics for ease of operation., Methods: Device performance was assessed in measurements of optical power output, spectral stability, and preclinical assessment of PDT response in ALA-photosensitized squamous carcinoma cell cultures and murine subcutaneous tumor xenografts., Results: The system achieves target optoelectronic performance with a stable battery-powered output of approximately 180 mW from the fiber tip within the desired spectral window for PpIX activation. The device has a compact configuration, user friendly operation and flexible light delivery for the oral cavity. In cell culture, we show that the overall dose-response is consistent with established light sources and complete cell death of ALA photosensitized cells can be achieved in the irradiated zone. In vivo PDT response (reduction in tumor volume) is comparable with a commercial 635 nm laser., Conclusions: We developed a low-cost, LED-based, fiber-coupled PDT light delivery source that has stable output on battery power and suitable form factor for deployment in rural and/or resource-limited settings. Lasers Surg. Med. 9999:1-7, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly killing tumor cells through heat and reactive oxygen species, PTT and PDT can also induce various antitumor effects. In particular, the resultant massive tumor cell death after PTT and PDT triggers immune responses, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. The antitumor effects can be enhanced by immune checkpoint blockage therapy. This article reviewed the recent advances of nanoparticle-based PTT and PDT, summarized the studies on nanoparticle-based photothermal and photodynamic immunotherapies in vitro and in vivo, and discussed challenges and future research directions., (© 2018 UICC.)

Objective: In the setting of lung cancer, photodynamic therapy (PDT) is typically used to treat centrally located endobronchial tumors. The development of navigational bronchoscopy has opened the potential for using PDT to treat peripheral lung tumors. However, there is limited information about the feasibility of this approach for treating peripheral lung cancers, and about its effects on surrounding healthy lung tissue. We studied the use of PDT delivered by electromagnetic navigational bronchoscopy to treat peripheral lung cancer in dogs., Materials and Methods: Three dogs with peripheral lung adenocarcinomas were given intravenous porfimer sodium (Photofrin® [Pinnacle Biologics, Inc., Chicago, IL]) to photosensitize the tumors, then navigational bronchoscopy was used to deliver photoradiation. One week after PDT, the tumors and involved lung lobe were surgically excised and evaluated histologically., Results: PDT was successful in all three dogs and was associated with tolerable and manageable adverse effects. Tissue sections from within PDT-treated tumors showed regions of coagulative central necrosis admixed with small numbers of inflammatory cells, and arterial thrombosis. Viable adenocarcinoma was seen in the surrounding areas., Conclusion: These results suggest that PDT can be successfully deployed to treat peripheral lung cancers using navigational bronchoscopy. Furthermore, damage to surrounding noncancerous tissues can be minimized with accurate placement of the optical fiber. Studies of this modality to treat peripheral lung cancers in humans may be warranted. Lasers Surg. Med. 50:483-490, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: Topical photodynamic therapy is an established treatment modality for various dermatological conditions, including actinic keratosis. In Europe, the approved protocols for photodynamic therapy of actinic keratosis involve irradiation with either an Aktilite CL 128 lamp or daylight, whereas irradiation with the Blu-U illuminator is approved in the United States. Many other protocols using irradiation by a variety of light sources are also clinically efficient., Objectives: This paper aims to compare 10 different protocols with clinically proven efficacy for photodynamic therapy of actinic keratosis and the available spectral irradiance of the light source. Effective irradiance, effective light dose, and local damage are compared. We also investigate whether there is an association between the complete response rate at 3 months and the effective light dose or local damage., Methods: The effective irradiance, also referred to as protoporphyrin IX-weighted irradiance, is obtained by integrating the spectral irradiance weighted by the normalized absorption spectrum of protoporphyrin IX over the wavelength. Integrating the effective irradiance over the irradiation time yields the effective light dose, which is also known as the protoporphyrin IX-weighted light dose. Local damage, defined as the total cumulative singlet oxygen molecules produced during treatment, is estimated using mathematical modeling of the photodynamic therapy process. This modeling is based on an iterative procedure taking into account the spatial and temporal variations in the protoporphyrin IX absorption spectrum during treatment., Results: The protocol for daylight photodynamic therapy on a clear sunny day, the protocol for daylight photodynamic therapy on an overcast day, the photodynamic therapy protocol for a white LED lamp for operating rooms and the photodynamic therapy protocol for the Blu-U illuminator perform better than the six other protocols-all involving red light illumination-in terms of both effective light dose and local damage. However, no association between the complete response rate at 3 months and the effective light dose or local damage was found., Conclusions: Protocols that achieve high complete response rates at 3 months and low pain scores should be preferred regardless of the effective light dose and local damage. Lasers Surg. Med. 50:576-589, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: Photodynamic therapy (PDT) is a minimally invasive treatment for malignant tumors. The aim of this study was to determine the efficacy of PDT in patients with head and neck squamous cell carcinoma (HNSCC)., Methods: Thirty-three patients with HNSCC were treated with porfimer sodium-mediated PDT followed by intraoperative light activation at 630 nm via fiber optic microlens delivered after 48 hours of injection., Results: The complete response (CR) rate was 72.7%, while the efficacy (CR + partial response) rate was 97.0%. The rate of good local control (i.e., CR without recurrence after PDT) achieved after the initial PDT (82.6%) was significantly higher than that achieved after the second or third PDT (10%); this rate remained at 62.1% without functional disturbance and disfigurement even after excluding four previously untreated patients. The final local control rate following PDT plus additional therapies was 73.8%., Conclusions: PDT is an effective therapy to treat HNSCC, and leads to an improved quality of life in patients with residual or recurrent disease. Lasers Surg. Med. 50:420-426, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Purpose: Photodynamic therapy (PDT) is a promising treatment modality to be added in the management of glioblastoma multiforme (GBM). Light distribution modeling is required for planning and optimizing PDT. Several models have been developed to predict the light propagation inside biological tissues. In the present study, two analytical methods of light propagation emitted from a cylindrical fiber source were evaluated: a discrete and a continuous method., Methods: The two analytical approaches were compared according to their fluence rate results. Several cylindrical diffuse lengths were evaluated, and the relative deviation in the fluence rates was estimated. Moreover, a sensitivity analysis was conducted to compute the variance of each analytical model., Results: The discrete method provided fluence rate estimations closer to the Monte-Carlo simulations than the continuous method. The sensitivity study results did not reveal significant differences between the variance of the two analytical models., Conclusions: Although the discrete model provides relevant light distribution, the heterogeneity of GBM tissues was not considered. With the improvement in parallel computing that drastically decreased the computing time, replacing the analytical model by a Monte-Carlo GPU-accelerated code appeared relevant to the GBM case. Nonetheless, the analytical modeling may still function in the optimization algorithms, which might be used in the Photodynamic treatment planning system. Lasers Surg. Med. 50:523-534, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objectives: To investigate the blood flow characteristics of polypoidal choroidal vasculopathy (PCV) using optical coherence tomography angiography (OCTA) and to analyse photodynamic therapy (PDT) effects on choroidal remodelling in PCV., Materials and Methods: Diagnostic indocyanine green angiography and OCTA were performed. All patients underwent PDT with full-dose verteporfin and were followed up with enhanced-depth imaging optical coherence tomography., Results: At baseline, a branching vascular network (BVN) was clearly demonstrated in all patients with PCV who underwent OCTA examinations as opposed to polyps. Additionally, the choroidal thickness (266 [range: 74-456] µm) showed a positive relationship with polyp size (0.59 [range: 0.33-0.94] mm 2 , r = 0.679, P = 0.0022). The subfoveal choroidal thickness and choroidal thickness at polyp sites increased within 1 day after PDT and atrophied 1-3 months after PDT., Conclusions: The differences in imaging characteristics between BVNs and polyps on OCTA were presumably due to both blood turbulence (different flow orientations) within polyps and the velocities detectable on OCTA. Moreover, the choroidal remodelling effects of PDT in PCV suggested the occurrence of transitional reactive inflammatory choroidal vascular hyperpermeability and choroidal exudation. PCV involved the entire choroids rather than only focal lesions. Lasers Surg. Med. 50:427-432, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: Patients suffering from malignant gliomas have a poor prognosis. For the surgical treatment of these tumors, 5-aminolevulinic acid (5-ALA) has become a new standard., Aims: This review intends to provide an overview over current status, significance, limitations, and future perspectives of 5-ALA based fluorescence guided surgery and photodynamic therapy for brain tumor patients., Materials and Methods: From peer reviewed publications on the many aspects connected with this topic, those with potential clinical relevance were selected and put in the context of our own experience., Results and Discussion: The high tumor selectivity of accumulation of fluorescent protoporphyrin IX (PpIX) after systemic administration of 5-ALA enables intra-operative fluorescence guidance, which is unimpaired by brainshift and does not require expensive equipment. The neurosurgical aim of complete resection of enhancing tumor can now more easily be achieved, which improves prognosis in these patients. Nevertheless, despite better surgery tumors will inevitably recur. In order to further prolong survival, the phototoxic properties of PpIX are presently being exploited in clinical trials of post-operative or interstitial photodynamic therapy (PDT)., Conclusion: 5-ALA based fluorescence guidance and PDT offer an intriguing new option for the management of malignant gliomas. Lasers Surg. Med. 50:399-419, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc., (© 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.)

Background: High-grade gliomas are primary brain tumors that have shown increasing incidence and unfavorable outcomes. Local control is crucial to the management of this pathology. Photodynamic therapy (PDT), based on the light-induced activation of a photosensitizer (PS), achieves local treatment by inducing selective lesions in tumor tissue., Objectives: Previous studies have reported the outcomes of PDT for glioblastoma via immunohistological data. Our study aimed to evaluate MRI findings, including diffusion, and perfusion sequences, compared with immunohistological data from the same population to address the efficiency of light fractionation., Materials and Methods: Twenty-six "nude" rats grafted with human U87 cells into the right putamen underwent PDT. After PS precursor (5-ALA) intake, an optical fiber was introduced into the tumor. The rats were randomized into the following groups: those without illumination and those that received two or five fractions of light. Treatment effects were assessed with early high-field MRI to measure the volume of necrosis and edema using diffusion and perfusion sequences; the MRI results were compared with immunohistology results, including necrosis and apoptosis markers., Results: Elevated diffusion values were observed on MRI in the centers of the tumors of the treated animals, especially in the 5-fraction group (P < 0.01). Perfusion was decreased around the treatment site, especially in the 5-fraction group (P = 0.024). The MRI findings were consistent with previously published histological data. The median volume of necrosis was significantly different between the sham group and treated groups, 0 mm 3 versus 2.67 mm 3 , P < 0.001. The same trend was previously observed in histology data when grading the absence or presence of necrosis and when the presence of necrosis was significantly more predominant for the treated group than for the untreated group (P < 001). Additionally, cell death represented by apoptosis marker data (TUNEL method) was significantly higher in the 5-fraction group than in the 2-fraction group (P = 0.01)., Conclusion: Diffusion and perfusion MRI revealed histological lesions. Interstitial PDT (iPDT) induced specific lesions in the tumor tissue, which were observed with MRI and confirmed by histopathological analysis. Thus, MRI may provide a non-invasive and reliable tool to assess treatment outcomes after PDT. Lasers Surg. Med. 50:460-468, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objective: The purpose of this study was to investigate the effect of two-step irradiance schedule in relieving pain during PDT of CA., Methods: The study was a prospective, controlled trial of 141 CA patients who were randomly divided into Group A (two-step irradiance schedule) and Group B (single-dose cold compress). The numeric rating scales (NRS) of patients' pain were recorded at 5, 10, 15, and 20 minutes during each PDT., Results: The efficacy of PDT and NRS scores of patients in the two groups were compared. There was no significant difference in gender, age, lesion site, and disease course between the two groups (P > 0.05). In addition, the cure rate of patients in the two groups was not significantly different (97.1% vs. 95.8%, χ 2  = 0.000, P = 1.000). However, the NRS scores at different time points and number of PDT sessions were significantly different (F = 198.233 and 165.224, respectively, P < 0.05). The NRS scores of patients in Group A were significantly lower than those of patients in Group B (F = 82.762, P < 0.0001). Moreover, the NRS scores at different positions were significantly different (F = 28.286, P < 0.0001). The NRS scores of penis were significantly lower than those of the vulva and crissum (P < 0.05)., Conclusions: Compared with single-dose cold compress, two-step irradiance schedule could more significantly reduce the patients' pain degree during treatment, especially for vulva and crissum. Lasers Surg. Med. 49:908-912, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Following photodynamic therapy with 5-aminolevulinic acid (ALA-PDT), patients experience inflammation that may be partially attributable to H1 histamine receptor activation. The objective of this study was to evaluate the impact of antihistamines upon adverse effects following ALA-PDT., Study Design/materials and Methods: This was a randomized, placebo-controlled clinical trial conducted at a single study site. Twenty subjects with facial actinic keratoses were randomized to ALA-PDT plus cetirizine 10 mg (n = 10) versus placebo daily (n = 10) from 3 days pre-treatment to 3 days post-treatment for a total of 7 days. Signs of inflammation including erythema, edema, crusting, exudation, vesiculation, and erosion were evaluated on post-treatment days 1, 2, 3, 7, 30, 90, and 180. Actinic keratosis counts, investigator-rated Global Assessment Improvement Score (GAIS), healing, tolerability, and subject satisfaction were also assessed., Results: Erythema, edema, crusting, exudation, vesiculation, and erosion were not different between treatment groups. Actinic keratoses were significantly reduced by day 30 in both the antihistamine and placebo groups (P = 0.01 and 0.0009, respectively), with results sustained to day 60 in the antihistamine group and day 180 for the placebo group. However, counts were not different between groups at any time point. Investigator-rated GAIS, subject satisfaction, healing, and tolerability were similar between treatment groups., Conclusion: This study suggests that while H1 antihistamines do not impair the efficacy of ALA-PDT, they also do not relieve post-treatment inflammation and discomfort. Lasers Surg. Med. 49:738-742, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Low-dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo-induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake., Material and Methods: In a pleural sarcoma and adenocarcinoma rat model (n = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm 2 ) followed by intravenous Lipoplatin® (5 mg/kg) administration. Tumor and normal tissue IFP were assessed before and up to 1 hour following photoinduction. Lipoplatin® uptake was determined 60 minutes following photoinduction. We then treated the pleura of tumor-free minipigs with high dose photodynamic therapy (PDT) (0.0625 mg/kg Visudyne®, 30 J/cm 2 , n = 5) followed by Lipoplatin (5 mg/kg) administration., Results: In rodents, photoinduction resulted in a significant decrease of IFP (P < 0.05) in both tumor types but not in the surrounding normal lung, equally exposed to light. Also, photoinduction resulted in a significant increase of Lipoplatin® uptake in both tumor types (P < 0.05) but not in normal lung. Tumor IFP variation and Lipoplatin® uptake fitted an inverted parabola. In minipigs, high dose photodynamic treatment resulted in pleural IFP increase of some animals which predicted higher Lipoplatin® uptake levels., Conclusion: Normal and tumor vasculatures react differently to PDT. Continuous IFP monitoring in normal and tumor tissues is a promising biomarker of vessel photoinduction. Moderate drop in tumor with no change in normal tissue IFP are predictive of specific Lipoplatin® uptake by cancer following PDT. Lasers Surg. Med. 49:773-780, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Alternative treatments are needed to achieve consistent and more complete port wine stain (PWS) removal, especially in darker skin types; photodynamic therapy (PDT) is a promising alternative treatment. To this end, we previously reported on Talaporfin Sodium (TS)-mediated PDT. It is essential to understand treatment tissue effects to design a protocol that will achieve selective vascular injury without ulceration and scarring. The objective of this work is to assess skin changes associated with TS-mediated PDT with clinically relevant treatment parameters., Study Design/materials and Methods: We performed TS (0.75 mg/kg)-mediated PDT (664 nm) on Sprague Dawley rats. Radiant exposures were varied between 15 and 100 J/cm 2 . We took skin biopsies from subjects at 9 hours following PDT. We assessed the degree and depth of vascular and surrounding tissue injury using histology and immunohistochemical staining., Results: TS-mediated PDT at 0.75 mg/kg combined with 15 and 25 J/cm 2 light doses resulted in vascular injury with minimal epidermal damage. At light dose of 50 J/cm 2 , epidermal damage was noted with vascular injury. At light doses >50 J/cm 2 , both vascular and surrounding tissue injury were observed in the forms of vasculitis, extravasated red blood cells, and coagulative necrosis. Extensive coagulative necrosis involving deeper adnexal structures was observed for 75 and 100 J/cm 2 light doses. Observed depth of injury increased with increasing radiant exposure, although this relationship was not linear., Conclusion: TS-mediated PDT can cause selective vascular injury; however, at higher light doses, significant extra-vascular injury was observed. This information can be used to contribute to design of safe protocols to be used for treatment of cutaneous vascular lesions. Lasers Surg. Med. 49:767-772, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objective and Study Design: Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling., Methods: This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated., Results: The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol., Conclusion: This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: To study the mechanisms of human glioblastoma cell resistance to methyl ester pyropheophorbide-a-mediated photodynamic therapy (MPPa-PDT) and the relationship between the cells and adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2)., Study Design/materials and Methods: The sensitivity of four human glioma cell lines (U87, A172, SHG-44, and U251) to MPPa-PDT was detected with a CCK-8 assay. Cell apoptosis, intracellular MPPa, and singlet oxygen were tested with flow cytometry. The mRNA and protein expression of ATP-binding cassette transporters (ABCG2, MRP1, and MDR1) were detected by PCR and Western blot, respectively., Results: Both the sensitivity to MPPa-PDT and intracellular MPPa in A172 were the lowest among the four cell lines, while expression of ABCG2 mRNA and protein in A172 were the highest. The intracellular MPPa and ROS in A172 receiving MPPa-PDT significantly increased after using the ABCG2 inhibitor fumitremorgin C (FTC). Both cell viability and apoptosis in A172 cells undergoing MPPa-PDT were significantly improved with FTC., Conclusions: ABCG2 plays a significant role in the resistance of A172 to MPPa-PDT. Lasers Surg. Med. 49:719-726, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: The estimated incidence of cutaneous squamous cell carcinoma (SCC) is 700,000 cases per year. In the US, SCC incidence is highest among fair skinned adults older than 50 years of age. Thus, as the population ages, the reported number of SCCs will likely increase in the future. Photodynamic therapy (PDT) is an FDA approved therapy for treatment of actinic keratoses (AKs), a precursor to cutaneous SCC lesions. The FDA approved incubation time of the photosensitizing agent 5-aminolevulinic acid (ALA) is 14-18 hours. Recent studies have investigated short ALA incubation times of 1-3 hours with ALA and PDT demonstrating treatment success. Therefore, the question exists whether ALA incubation periods of less than 30 minutes are efficacious. Herein, we evaluate the efficacy of short ALA incubation periods by measuring apoptosis after 10, 15, and 20 minutes of ALA incubation., Study Design/materials and Methods: AG13145 normal human dermal fibroblasts HDFs were incubated with 10, 15, or 20 minute of ALA at various concentrations (0, 0.05, 0.075, 0.1, 0.25, 0.375, 0.5, 1, and 2 mM). After ALA incubation, samples were treated with 1,000 seconds (16 minutes 40 seconds) of Blu-U fluorescent blue light (417 ± 5 nm) for a fluence of 10 J/cm 2 . Immediately following treatment with blue light, samples were collected and stained for apoptosis and necrosis with annexin-V and 7-aminoactinomycin D (7-AAD), and then analyzed by flow cytometry., Results: HDFs incubated with ALA for 10 minute at 36 °C followed by 10 J/cm 2 of blue light had no statistically significant changes in apoptosis. HDFs incubated with ALA for 15 or 20 minutes at 36 °C followed by 10 J/cm 2 of blue light had statistically significant increases in the percentages of cells positive for apoptosis in the 0.5, 1.0, and 2.0 mM ALA doses (P < 0.05)., Conclusions: We found that incubation of ALA for at least 15 minutes followed by 10 J/cm 2 of blue light resulted in a statistically significant increase in apoptosis. Lasers Surg. Med. 49:592-598, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objectives: Image-based treatment planning can be used to compute the delivered light dose during interstitial photodynamic therapy (I-PDT) of locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The objectives of this work were to evaluate the use of surface fiducial markers and flexible adhesive grids in guiding interstitial placement of laser fibers, and to quantify the impact of discrepancies in fiber location on the expected light dose volume histograms (DVHs)., Methods: Seven gel-based phantoms were made to mimic geometries of LA-HNSCC. Clinical flexible grids and fiducial markers were used to guide the insertion of optically transparent catheters, which are used to place cylindrical diffuser fibers within the phantoms. A computed tomography (CT) was used to image the markers and phantoms before and after catheter insertion and to determine the difference between the planned and actual location of the catheters. A finite element method was utilized to compute the light DVHs. Statistical analysis was employed to evaluate the accuracy of fiber placement and to investigate the correlation between the location of the fibers and the calculated DVHs., Results: There was a statistically significant difference (P = 0.018) between all seven phantoms in terms of the mean displacement. There was also statistically significant correlation between DVHs and depth of insertion (P = 0.0027), but not with the lateral displacement (P = 0.3043). The maximum difference between actual and planned DVH was related to the number of fibers (P = 0.0025) and the treatment time., Conclusions: Surface markers and a flexible grid can be used to assist in the administration of a prescribed DVH within 15% of the target dose provided that the treatment fibers are placed within 1.3 cm of the planned depth of insertion in anatomies mimicking LA-HNSCC. The results suggest that the number of cylindrical diffuser fibers and treatment time can impact the delivered DVHs. Lasers Surg. Med. 49:599-608, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background: Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a localized treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen, which results in the formation of cytotoxic species. The delivery of fractionated light may enhance treatment efficacy by reoxygenating tissues., Objective: To evaluate the efficiency of two light-fractionation schemes using immunohistological data., Materials and Methods: Human U87 cells were grafted into the right putamen of 39 nude rats. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomly divided into three groups: without light, with light split into 2 fractions and with light split into 5 fractions. Treatment effects were assessed using brain immunohistology., Results: Fractionated treatments induced intratumoral necrosis (P < 0.001) and peritumoral edema (P = 0.009) associated with a macrophagic infiltration (P = 0.006). The ratio of apoptotic cells was higher in the 5-fraction group than in either the sham (P = 0.024) or 2-fraction group (P = 0.01). Peripheral vascularization increased after treatment (P = 0.017), and these likely new vessels were more frequently observed in the 5-fraction group (P = 0.028)., Conclusion: Interstitial PDT with fractionated light resulted in specific tumoral lesions. The 5-fraction scheme induced more apoptosis but led to greater peripheral neovascularization. Lasers Surg. Med. 49:506-515, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Current osteosarcoma therapies cause severe treatment-related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti-vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark- and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20-tetrakis(meta-hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2-derived osteosaroma cell line (K7M2L2) in vitro. Second, the tumor- and metastasis-suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time- and dose-dependent and resulted in mTHPC and light dose-dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan p < 0.05, Foslip p < 0.001) tumor growth inhibition in both models. A significant (Foscan p < 0.001, Foslip p < 0.001) immune system-dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T-lymphocytes at the primary tumor site. In conclusion, mTHPC-based PDT is effective in clinically relevant experimental osteosarcoma and suppresses lung metastasis in immunocompetent mice with beneficial effects of the liposomal mTHPC formulation Foslip., (© 2016 UICC.)

Introduction: The non-invasive vulvar Paget's disease is an intra-epidermal carcinoma with glandular characteristics. It appears like an erythematous plaque. The main symptoms are pruritus and pain. The standard treatment is surgical excision in depth. This treatment is complicated with a severe morbidity and photodynamic therapy can be an alternative choice. However, the pain experienced during the photodynamic treatment of vulvar lesion is intense and leads to a premature interruption of the treatment. The light emitting fabric is a part of a device under clinical evaluation for the treatment of actinic keratosis with photodynamic therapy. We report the observation of a vulvar Paget's disease treated by this device with a satisfactory result and an excellent tolerance., Clinical Observation: The patient has been diagnosed with non-invasive vulvar Paget's disease for 25 years. The disease recurred constantly despite several imiquimod applications, LASER treatments and conventional photodynamic therapy. These procedures were complicated with intense pain. To improve the tolerance, we performed three PDT sessions a month apart using a 16% methyl-aminolevulinate cream (Metvixia® Galderma, Lausanne, Switzerland) with the light emitting fabric at low irradiance (irradiance = 6 mW/cm 2 -fluence = 37 J/cm 2 ) with a satisfactory result and an excellent tolerance., Discussion: There are no controlled trials evaluating the efficacy of photodynamic therapy in the treatment of vulvar Paget's disease. The treatment and follow-up protocols in the literature are heterogeneous. Pain is the most common side effect with greater intensity for perineal locations where photodynamic therapy is impractical outside of anesthesia or hypnosis., Conclusion: We report the case of a multirecidivant non-invasive vulvar Paget's disease treated with a satisfactory result and an excellent tolerance by the new light emitting fabric device. A specific study is required but the light emitting fabric could be indicated for the treatment of Paget disease of perineal location. Lasers Surg. Med. 49:177-180, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Photodynamic therapy (PDT) has been used as a therapeutic alternative to treat periodontitis, especially in challenging sites that require additional periodontal therapy such as residual pockets. The aim of this split-mouth randomized trial was to evaluate the microbiological and clinical effects of PDT on non-surgical treatment of unresponsive pockets., Study Design/materials and Methods: A split-mouth, randomized controlled clinical trial was conducted in 15 patients presenting at least two residual pockets (probing pocket depth [PPD] ≥5 mm with bleeding on probing [BoP]) in single-rooted teeth in supportive periodontal therapy. The selected sites randomly received: (1) SRP + PDT: scaling and root planing combined with photodynamic therapy (methylene blue as a photosensitizer), or (2) SRP: scaling and root planing alone. The concentrations of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were evaluated using a Real-time PCR technique at baseline and 3, 7, 14, and 90 days. Clinical parameters were assessed at baseline and 3 months post-therapies., Results: Both treatments promoted clinical improvements, with additional benefits to the SRP + PDT group in PPD reduction and clinical attachment level gain (P < 0.05) after 3 months. Only the SRP + PDT group exhibited a statistically significant reduction in the levels of A. actinomycetemcomitans on the 3rd and 7th days after therapy (P < 0.05), and a lower concentration of this pathogen was detected at 7 days in the SRP + PDT group when compared to the other therapy (P < 0.05)., Conclusion: The combined therapeutic approach SRP + PDT may reduce A. actinomycetemcomitans levels for a short-term period, associated with additional improvement in clinical parameters in treating residual pockets. Lasers Surg. Med. 48:944-950, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)