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1.
Topical treatment with oleocanthal extract in reducing inflammatory reactions after photodynamic therapy: a prospective quasi-experimental pilot study.
Segura Palacios, JM, Blázquez Sánchez, N, Rivas Ruiz, F, Aguilar Bernier, M, Ramírez López, B, Sánchez, MEF, de Troya Martín, M
Complementary therapies in medicine. 2019;:298-301
Abstract
OBJECTIVE Photodynamic therapy (PDT) is an effective treatment against skin field cancerization. Its main side effect is local inflammation in the treated area. The phenolic compound oleocanthal (decarboxy methyl ligstroside aglycone), which is present in extra virgin olive oil (EVOO), has anti-inflammatory properties. The purpose of this study was to evaluate the topical efficacy of an oily fluid enriched with oleocanthal (OC) extract, in comparison with a conventional oily fluid, in reducing the degree of inflammatory reaction after conventional PDT. METHODS Quasi-experimental pilot study, before-after with a control group, performed with a cohort of consecutive patients diagnosed with actinic keratosis/field cancerization (AK/FC) in the forehead and/or scalp, treated by PDT. The study was carried out from April 2016 to November 2017 at a speciality hospital in southern Spain. A group of 24 consecutive patients received the topical application, three times daily for one week, of an emollient oily fluid in the area treated with PDT. Subsequently, another group, of 23 consecutive patients, received the same treatment pattern with an oily fluid enriched with OC extract. The post-PDT inflammatory reaction was measured by an independent member of the hospital's dermatology department, using the following visual scale of erythema (from 0 to 4).The assessment was conducted at 30 min and at 48 h post-PDT. RESULTS In the assessment at 48 h after treatment, the inflammation had improved more among the patients treated with OC (median: 25%, 95%CI: -5.3 to 28.5) than in the non-OC group (median: 0%; 95%CI: -45.2 to -6.2). The difference was statistically significant (p<0.01), and the Cohen's d value was 0.89 (large effect). At three months after PDT, a complete response had been obtained by 60.9% of the patients treated with OC compared to 29.2% of the non-OC group, and the difference was close to statistical significance (p=0.059). CONCLUSIONS The topical application of an oily fluid enriched with OC extract achieved a greater reduction in post-PDT cutaneous inflammation and a better treatment response, in comparison with the application of a conventional oily fluid.
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2.
Combination of tacalcitol ointment and photodynamic therapy for the treatment of follicular mucinosis of the scalp.
Giuffrida, R, Borgia, F, Marafioti, I, Riso, G, Cannavò, SP
Photodiagnosis and photodynamic therapy. 2019;:487-489
Abstract
Follicular mucinosis (FM) is a rare inflammatory disorder histologically characterized by mucin deposition in the follicular epithelium. There is no standard therapy for FM and several treatments have been described in the literature. We present the case of a 59 year-old female affected by a recalcitrant FM with diffuse scalp alopecia, in which complete clinical remission was achieved after a combination of topical tacalcitol and photodynamic therapy.
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3.
Improving in vitro photodynamic therapy through the development of a novel iron chelating aminolaevulinic acid prodrug.
Curnow, A, Perry, A, Wood, M
Photodiagnosis and photodynamic therapy. 2019;:157-165
Abstract
BACKGROUND Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of cancers and precancers. It is particularly useful in its topical form in dermatology but improvement of efficacy is required to widen its application. METHODS An ester between aminolaevulinic acid (ALA) and CP94 was synthesised (AP2-18) and experimentally evaluated to determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could be improved. A biological evaluation of AP2-18 was conducted in cultured human primary cells with both PpIX fluorescence and cell viability (as determined via the neutral red assay) being assessed in comparison to the PpIX prodrugs normally utilised in clinical practice (aminolaevulinic acid (ALA) or its methyl ester (MAL)) either administered alone or with the comparator iron chelator, CP94. RESULTS No significant dark toxicity was observed in human lung fibroblasts but AP2-18 significantly increased PpIX accumulation above and beyond that achieved with ALA or MAL administration +/- CP94 in both human dermal fibroblasts and epithelial squamous carcinoma cells. On light exposure, the combined hydroxypyridinone iron chelating ALA prodrug AP2-18 generated significantly greater cytotoxicity than any of the other treatment parameters investigated when the lowest concentration (250 μM) was employed. CONCLUSIONS Newly synthesised AP2-18 is therefore concluded to be an efficacious prodrug for PpIX-induced PDT in these dermatologically relevant human cells, achieving enhanced effects at lower concentrations than currently possible with existing pharmaceuticals.
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4.
Corneal crosslinking: Current protocols and clinical approach.
Beckman, KA, Gupta, PK, Farid, M, Berdahl, JP, Yeu, E, Ayres, B, Chan, CC, Gomes, JAP, Holland, EJ, Kim, T, et al
Journal of cataract and refractive surgery. 2019;(11):1670-1679
Abstract
Members of the ASCRS Cornea Clinical Committee performed a review of the current literature on the corneal crosslinking (CXL) procedure for treating corneal ectasia. The members explored the data on the techniques currently in use and under investigation, including their advantages, safety profiles, risks, and cost analyses, compared with data on corneal transplantation. They concluded that CXL limits the progression of keratoconus, thus reducing the need for transplantation. They also found that compared with permitting the disease to progress naturally, CXL techniques carry significant and long-term cost and safety benefits, primarily by reducing the need for corneal transplantation. Studies of various CXL techniques (eg, epithelium-on treatment, changes in ultraviolet light parameters, riboflavin composition) continue with the ultimate goal of improving the procedure's safety and efficacy.
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5.
Phase 1 study of EUS-guided photodynamic therapy for locally advanced pancreatic cancer.
DeWitt, JM, Sandrasegaran, K, O'Neil, B, House, MG, Zyromski, NJ, Sehdev, A, Perkins, SM, Flynn, J, McCranor, L, Shahda, S
Gastrointestinal endoscopy. 2019;(2):390-398
Abstract
BACKGROUND AND AIMS Locally advanced pancreatic cancer (LAPC) has a poor prognosis. There are limited data describing the use of photodynamic therapy (PDT) for pancreatic cancer in humans. We hypothesized that EUS-guided PDT for LAPC is safe, technically feasible, and produces a dose- and time-dependent increasing degree of image-defined tumor necrosis. METHODS In a single-center, prospective, dose-escalation phase 1 study, patients with treatment-naïve LAPC received intravenous porfimer sodium (Concordia Laboratories Inc, St Michael, Barbados) followed 2 days later by EUS-PDT. EUS-PDT was performed by puncture with a 19-gauge needle and insertion of a 1.0-cm light diffuser (Pioneer Optics, Bloomfield, Conn) and illumination with a 630-nm light (Diomed Inc, Andover, Mass). A CT scan 18 days after PDT was done to assess for change in pancreatic necrosis. Nab-paclitaxel (125 mg/ m2 intravenously) and gemcitabine (1000 mg /m2 intravenously) were initiated 7 days after CT and given weekly for 3 of 4 weeks (1 cycle) until disease progression or unacceptable toxicity. RESULTS Twelve patients (mean age, 67 ± 6 years; 8 male) with tumors (mean diameter, 45.2 ± 12.9 mm) in the head and/or neck (8) or body and/or tail (4) underwent EUS-PDT. Compared with baseline imaging, increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%) after EUS-PDT. The mean overall increases in volume and percentage necrosis were 10 ± 26 cm3 (P = .20) and 18% ± 22% (P = .016), respectively. After a median follow-up of 10.5 months (range, 1.0-37.4 months), median progression-free (PFS) and overall survival (OS) were 2.6 months (95% confidence interval, 0.7, not estimable) and 11.5 months (95% confidence interval, 1.1, 16.9), respectively. Surgical resection was attempted in 2 patients, and pathology showed a complete response (n = 1) and residual 2-mm tumor (n = 1). There were 8 serious adverse events and none related to EUS or EUS-PDT. CONCLUSION EUS-PDT for LAPC appears to be safe and produces measurable imaged-defined tumor necrosis. Phase 2 studies are warranted. (Clinical trial registration number: NCT01770132.).
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6.
Randomized Study of Collagen Cross-Linking With Conventional Versus Accelerated UVA Irradiation Using Riboflavin With Hydroxypropyl Methylcellulose: Two-Year Results.
Hagem, AM, Thorsrud, A, Sandvik, GF, Drolsum, L
Cornea. 2019;(2):203-209
Abstract
PURPOSE To compare the clinical outcome 2 years after corneal collagen cross-linking (CXL) with conventional and accelerated ultraviolet A (UVA) irradiation using riboflavin with hydroxypropyl methylcellulose. METHODS Prospective randomized controlled study. Forty patients with keratoconus (40 eyes) were randomized to either CXL using conventional 3 mW/cm UVA irradiation for 30 minutes (CXL30 group) or accelerated 9 mW/cm UVA irradiation for 10 minutes (CXL10 group). In both groups, a solution of 0.1% riboflavin with 1.1% hydroxypropyl methylcellulose (methylcellulose-riboflavin) was used. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and Scheimpflug tomography were performed at baseline and after 24 months. RESULTS Both groups had statistically significant improvement in CDVA and maximum keratometric reading compared with baseline; however, with no statistically significant difference in the change between the 2 groups. No significant changes in flattest, steepest and mean keratometry (K1, K2 and K mean) were found in either of the groups. There were no statistically significant changes in ECD in either group after 2 years or in the difference in the change between the 2 groups. A literature review showed comparative clinical outcome after accelerated CXL compared with conventional CXL; however, in several studies, there was a tendency for less pronounced corneal flattening after accelerated CXL. CONCLUSIONS Improvement in visual acuity and maximum keratometric reading 2 years after CXL was found after both conventional and accelerated UVA irradiation using methylcellulose-riboflavin. This suggests that when using riboflavin with methylcellulose, the less time-consuming accelerated protocol is a valuable and effective option in CXL treatment.
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7.
Role of photodynamic therapy in the treatment of esophageal cancer.
Wu, H, Minamide, T, Yano, T
Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2019;(5):508-516
Abstract
Photodynamic therapy (PDT), a treatment of choice for cancer, induces a photochemical reaction, thereby eradicating tumor cells. This is achieved through the administration of a photosensitizer drug, which is activated with a laser after localization to the tumor mass, and is an approved curative endoscopic ablative treatment for superficial esophageal squamous cell carcinoma (ESCC) in Japan. PDT has been approved for dysplastic Barrett's esophagus and as a palliative treatment for patients with symptomatic obstructive esophageal cancer in US. However, its adverse events and complicated procedure and the development of alternative endoscopic procedures such as endoscopic submucosal dissection, radiofrequency ablation and cryotherapy, have largely limited the practice of PDT in esophageal cancer worldwide. Recently, owing to the invention of second-generation PDT using talaporfin sodium and diode laser, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. As a salvage treatment for patients with local failure after chemoradiotherapy (CRT), PDT has shown promising complete response with less phototoxicity and shorter sun shade period. In addition, the efficacy and safety of PDT in patients with local failure of ESCC after CRT were shown in several clinical trials. The direction of the study interest of the next-generation PDT is the safety and potential expansion of the indications for its application in the future. This review covers the PDT for the treatment of ESCC and dysplastic Barrett's esophagus, with special focus on the role of PDT in practice for esophageal cancer.
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8.
Noninvasive real-time assessment of riboflavin consumption in standard and accelerated corneal crosslinking.
Lombardo, M, Lombardo, G
Journal of cataract and refractive surgery. 2019;(1):80-86
Abstract
PURPOSE To estimate the noninvasive riboflavin concentration in the corneal stroma using a new ultraviolet-A (UVA) theranostic device for corneal crosslinking (CXL). SETTING Vision Engineering Italy srl, Rome, Italy. DESIGN Experimental study. METHODS Fourteen human donor corneas were treated according to conventional (UVA irradiance of 3 mW/cm2 for 30 minutes) and rapid (10 mW/cm2 for 9 minutes) riboflavin-UVA CXL protocols using a theranostic UVA device. Five additional samples were treated by 0.5 mW/cm2 for 9 minutes and used as positive controls to determine riboflavin photodegradation under near ambient lighting conditions. A 20% dextran-enriched 0.1% riboflavin solution was used in all cases. The device consisted of a UVA light source; a red-green-blue camera, which acquires the fluorescence images of the cornea during treatment; and a single-board computer for managing the overall operations and the raw data processing. RESULTS Preirradiation stromal soaking for 30 minutes achieved highly consistent intrastromal riboflavin concentration in all tissues (mean 0.015% ± 0.003% [SD]). There were no differences in the kinetics curves of riboflavin consumption between the 2 UVA irradiation protocols; the intrastromal riboflavin concentration decreased exponentially, with a mean constant energy rate of 2.8 ± 0.2 J/cm2. In the control group, the intrastromal riboflavin concentration decreased quasilinearly. CONCLUSIONS The theranostic device provided estimates of the intrastromal concentration of riboflavin noninvasively during treatment. In the 3 to 10 mW/cm2 range of power densities, the consumption of riboflavin in the stroma by UVA irradiation was only energy dependent in accordance with the Bunsen-Roscoe law.
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9.
Two-year follow-up of corneal cross-linking and refractive surface ablation in patients with asymmetric corneal topography.
Malta, JBNS, Kaz Soong, H, Moscovici, BK, Campos, M
The British journal of ophthalmology. 2019;(1):137-142
Abstract
AIMS: To evaluate the safety and efficacy of corneal cross-linking (CXL) followed by photorefractive keratectomy (PRK) for refractive correction in patients with bilateral asymmetric topography. METHODS Forty-four patients (88 eyes) were enrolled in this prospective randomised clinical trial. CXL with subsequent PRK after 6 months was performed in one eye (study group), and PRK alone was performed in contralateral eyes (control group). Patients were followed for 24 months after PRK. Outcome measures investigated included visual acuity (VA), refraction, aberrometry, topography, pachymetry and endothelial cell count. Groups were compared with linear mixed regression and repeated measures logistic regression. Multiple comparison adjustment with the Holm procedure was performed. RESULTS At baseline, the logMAR VA (best spectacle corrected) in study and control groups was 0.12±0.13 (mean±SD) and 0.08D±0.14, respectively, and axial inferior-superior index (IS) (topographic IS) in study and control groups were 0.59D±0.31D and 0.58D±0.32D, respectively. After 24 months, a mean under correction of -0.50D was observed in both groups. Change from baseline in logMAR VA in study and control groups was 0.00D±0.08D and -0.02D±0.10D, respectively. Frequency of haze at 30 months in study and control group eyes was, respectively, 18.2% and 4.6% (p=0.05). There was no statistical difference between groups in spherical aberration and coma after adjustment for multiple comparisons. CONCLUSIONS Non-simultaneous CXL followed by PRK may be performed safely, and refractive results over a 2-year follow-up are highly similar in virgin and previously cross-linked corneas. Despite using mitomycin C, corneal haze can be significantly higher in the first year after PRK in eyes pretreated with CXL.
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10.
Advances in the application of upconversion nanoparticles for detecting and treating cancers.
Li, K, Hong, E, Wang, B, Wang, Z, Zhang, L, Hu, R, Wang, B
Photodiagnosis and photodynamic therapy. 2019;:177-192
Abstract
The detection and treatment of cancer cells at an early stage are crucial for prolonging the survival time and improving the quality of life of patients. Upconversion nanoparticles (UCNPs) have unique physical and chemical advantages and likely provide a platform for detecting and treating cancer cells at an early stage. In this paper, the principle of UCNPs as chemical sensors based on fluorescence resonance energy transfer (FRET) has been briefly introduced. Research progress in such chemical sensors for detecting and analyzing bioactive substances and heavy metal ions at the subcellular level has been summarized. The principle of UCNP-based nanoprobe-targeting of cancer cells has been described. The research progress in using nanocomposites for cancer cell detection, namely cancer cell targeted imaging and tissue staining, has been discussed. In the field of cancer treatment, the principles and research progress of UCNPs in photodynamic therapy and photothermal therapy of cancer cells are systematically discussed. Finally, the prospects for UCNPs and remaining challenges to UCNP application in the field of cancer diagnosis and treatment are briefly described. This review provides powerful theoretical guidance and useful practical information for the research and application of UCNPs in the field of cancer.