A clinical evaluation of the efficacy of photodynamic therapy in the treatment of erosive oral lichen planus: A case series

BackgroundErosive oral lichen planus (EOLP) poses a substantial risk of malignant transformation into squamous cell cancer. The absence of established treatment gives way to alternative therapeutic strategies, including photodynamic therapy. The aim of the study was to evaluate the efficacy of PDT in the treatment of EOLP.MethodsTwelve female patients aged 63–80 with 22 OLP lesions (16 on the buccal mucosa, 6 on gingiva and tongue), underwent authors’ own PDT scheme with the use of 5% solution of 5-aminolevulinic acid (ALA) as photosensitizer. An ALA-saturated occlusive dressing was applied directly onto a lesion and surrounding mucosa 2 h prior to illumination with a custom-made diode lamp (light of 630 nm, dose of 300 mW). After a series of 10 weekly illumination sessions the patients were monitored for 12 months.ResultsThe mean size of lesions before treatment was 1.46 cm² ± 1.44. The lesions on the buccal mucosa were smaller (1.06 cm² ± 0.98) than those on the gingiva and tongue (2.63 cm² ± 1.93). Post-treatment improvement encompassed 16 lesions, 5 of which were in remission. The mean reduction in size after 10-session therapy was 8,05%. The healing continued and further reduction in size (by 69.13%) took place during the 12-month observation: 39.62% of lesions within the buccal mucosa and full remission of all lesions on the gingiva and tongue.ConclusionsThe results suggest that PDT offers non-invasive treatment of lesions in oral mucosa and may become an alternative and complementary method to those currently in use. Further studies involving larger groups of patients should be undertaken before it becomes routine practice.     

Treatment of unresectable extrahepatic cholangiocarcinoma using hematoporphyrin photodynamic therapy: A prospective study

BackgroundThe available evidence of Photodynamic therapy (PDT) combined with stent placement treatment for unresectable extrahepatic cholangiocarcinoma (EHCC) is still insufficient. It also remains unclear whether PDT influences systemic inflammatory response.AimTo explore the clinical efficacy and safety of the combination treatment and the systemic inflammatory response in patients with EHCC.MethodsPatients with unresectable EHCC underwent either the combined treatment using Hematoporphyrin PDT and stent placement (PDT + stent group, n = 12) or stent-only (stent group, n = 27). The primary end-point was overall survival. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. Quality of life was assessed using the Karnofsky performance scale (KPS) every 3 months.ResultsAverage survival time (13.8 vs. 9.6 months), and 6-month (91.7% vs. 74.1%), and 1-year (58.3% vs. 3.7%) survival rates of PDT + stent group were significantly increased compared with the stent group. KPS scores in the PDT + stent group were significantly improved. TNF-α and IL-6 levels were significantly increased in the PDT + stent group.ConclusionHematoporphyrin-PDT combined with stent placement is an effective and safe treatment for EHCC. The treatment might promote systemic inflammatory response.     

Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma

BackgroundPhotodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor.ObjectiveTo assess methylene blue (MB) as a PDT agent for the treatment of respiratory tract cancer in animal models.MethodsMB-induced PDT was performed on 7 subcutaneous NCI-H460 lung adenocarcinoma xenografts in nude mice and 9 induced squamous cell cancer in the hamster cheek pouch model. In mice, PDT was carried out on right-sided tumors after intratumoral injection of methylene blue 1% (w/v) and illumination at 630 nm at 200 J/cm (Diomed PDT 630), with the left tumor used as control (illumination alone or MB alone). The tumoral volume was assessed before and 15 days after PDT.ResultsFourteen xenografts were treated in mice, including seven treated with MB-PDT, producing a 52% mean tumor volume regression (1568 mm³ vs. 544 mm³) compared to seven control cases in which tumor volume increased (p = 0.007; Mann-Whitney test). Nine cheek pouch induced carcinomas were treated in the hamster group, with a mean volume decrease of 85.8% (from 44.8% to 100%) (initial mean volume = 210 mm³ vs. post PDT mean volume = 97 mm³). Histology analysis showed 4/9 complete responses.ConclusionIntratumoral MB appears efficient as PDT agent for cancer treatment in animal models. Further studies are needed to assess the safety and efficacy of MB-associated PDT for the treatment of lung cancer in humans.     

Photodynamic therapy in the management of basal cell carcinoma: Retrospective evaluation of outcome

IntroductionPhotodynamic therapy (PDT) is a relatively new method of treating various kinds of pathologies. In this retrospective study, a total of 148 patients with basal cell carcinoma (BCC) were treated with surface illumination methyl aminolevulinate – photodynamic therapy (MAL-PDT) or meta-tetrahydroxyphenylchlorin (mTHPC-PDT). Comparisons with the clinical features, rate of recurrence and overall outcome were made.Materials and methodsSurface illumination PDT was offered under local or general anaesthesia. For thin BCCs, the 16% strength cream (MAL) was applied topically 3 h prior to tissue illumination. A single-channel 628 nm diode laser was used for illumination and light was delivered at 100J/cm² per site. For thick BCCs, 0.05 mg/kg mTHPC was administered intravenously prior to tissue illumination. A single-channel 652 nm diode laser was used for illumination and light was delivered at 20J/cm² per site. Lesion response evaluation was carried out according to RECIST.ResultsThe MAL-PDT sub-group included 86 patients with 127 thin BCCs; 80 patients had complete response (CR) after one round of treatment. The mTHPC-PDT sub-group included 62 patients with 116 thick BCCs; 60 patients had complete response after one round of treatment. Statistically significant factors associated with complete response to MAL-PDT included superficial BCC histotype (P < 0.001), ≤0.5 mm tumour thickness (P < 0.001) and lack of ulceration (P < 0.001). While for the mTHPC-PDT sub-group, both superficial and nodular types responded significantly better than invasive type (P < 0.001); the lack of ulceration was insignificant factor in achieving complete response.ConclusionPDT achieved high efficacy in the treatment of basal cell carcinomas with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients.     

Treatment of peritoneal carcinomatosis with photodynamic therapy: Systematic review of current evidence

BackgroundPeritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis.MethodsWe systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017).ResultsThree human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15–300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0–4 [4 = highest]: PDT 3.4 ± 1.0 vs. control 0.4 ± 0.6, p < 0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p < 0.001).ConclusionPDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.     

Photodynamic therapy: An option in mycosis fungoides

BackgroundPhotodynamic therapy (PDT) is a well-known and effective treatment for non-melanoma skin-cancer. Numerous studies have also shown its effectiveness in mycosis fungoides. The aim of the study was to analyse MF patients treated with PDT at the Dermatology Unit of Bologna University.MethodsWe retrospectively analysed MF patients treated with PDT over the last ten years. Each PDT protocol consisted of the appliance for 3 h under an occlusive film dressing on each lesion of a one-mm-thick layer of 16% methyl aminolaevulinate (MAL) 160 mg/g cream (Metvix^®, Galderma, Paris, France). The cream was then removed and the skin was exposed to 630 nm red light from a diode lamp (Aktilite^®, Galderma Benelux, Rotterdam, the Netherlands), with a total radiation dose of 37 J/cm2 for 9 mins. A protocol of one session every month was scheduled. The treated lesions were clinically examined, before each treatment.ResultsFour cases, three male and one female, had been treated with PDT. Two patch lesions on the plantar area, one leg and the pubic area were treated. The number of PDT sessions ranged from 4 to 9. Two complete remissions and two partial remissions were observed. A low-to-mild burning sensation was reported during the treatment, and persisted over the next day; no further side effects were observed.ConclusionsOur series shows that PDT can be considered an effective second-line treatment in patients characterised by a disease located in difficult-to-treat anatomical areas such as the feet and the pubic area.     

Retrospective analysis of therapeutic effect and prognostic factors on early glottic carcinoma

ObjectiveTo investigate the therapeutic effect of surgery, radiotherapy and photodynamic therapy on early glottic carcinoma and prognostic factors.MethodsRetrospective analysis of 202 cases with early glottic carcinoma (Tis-T2N0M0) underwent surgery (n = 152), radiotherapy (n = 20) and PDT (n = 30) from 2000 to 2013 The KPS score, the disease-free survival (DFS), overall survival (OS), local control (LC), larynx preservation rate, laryngeal function were evaluated. The methods of χ ²test or Fisher's exact probability method, Kaplan Meier method, log-rank test of Kaplan-Meier method, Cox proportional hazards model were used to analyze the data.ResultsThere was no statistical significance in OS, DFS and LC among the three groups. The laryngeal function preservation rate of RT group, PDT group and Surgery group were 90%, 86.7% and 65.1% respectively, with the former two groups significantly superior to Surgery group. While there is no statistical significance between RT group and PDT group. Single factor analysis showed that KPS score before treatment, vocal fold mobility limitation and differentiation degree could have an effect on prognosis. Multivariate regression analyses indicated that anterior commissure invasion, T stage and KPS score before treatment were independent adverse prognostic factors for OS. T stage and differentiation degree were adverse prognostic factors for DFS. T stage was also an adverse factor of LC. Thirty-three cases experienced local recurrence or cervical lymph node metastasis. Three groups showed no statistical difference in local recurrence or lymph node metastasis, with twenty-two cases in Surgery group, four in RT group and seven in PDT group.ConclusionsThe therapeutic effect was approximate in surgery group, radiotherapy group and photodynamic group, and all three treatment regimens achieved good clinical effect. Radiotherapy and photodynamic therapy may be the first or very important treatment on early stage glottic squamous cell cancer (Tis ∼ T₂N₀M₀). However only 6 patients underwent PDT for T2 disease, making definitive treatment conclusions for this subgroup unclear.     

Skin fluorescence following photodynamic therapy with NPe6 photosensitizer

BackgroundThe second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period.MethodsThe NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10 min after NPe6 administration as well as at the time of PDT (4–5 h after administration), at discharge (2 or 3 days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT.ResultsNine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2–3 days after administration) in most cases and it decreased at 1 or 2 weeks after PDT.ConclusionsThe fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT.     

Knowledge,behavior and attitudes of dental practitioners towards photodynamic therapy use in dental practice

BackgroundThe aim of the present study was to assess knowledge, behavior and attitudes of dental practitioners (DPs) towards photodynamic therapy (PDT) in dental clinical practice.MethodsA cross-sectional study was performed and a 13-item survey questionnaire was given to DPs practicing in 13 different teaching hospitals in Karachi, Pakistan. Questions were aimed at exploring the knowledge of DPs regarding PDT and their attitude towards PDT and perceptions that may influence clinical practices. Chi-square and spearman coefficient were conducted to compare subgroups and correlate factors with the knowledge score of DPs.ResultsA total of 509 questionnaires were completed (response rate = 82%). Median age of participants was 34 years and 70% were females. Most DPs demonstrated good knowledge related to PDT, and nearly 77%, 69% and 62% were aware of the mechanism of action and the role of photosensitizers in PDT respectively. It was reported that 74% of the respondents expressed that they are comfortable to know about PDT in detail for their clinical practice. A cumulative 54% disagreed that discussing the option for PDT with their patients was peripheral to their role as clinicians. A striking 82% would like to attend seminars and workshops on PDT. Significant difference was found among senior lecturers and assistant professors for the knowledge items (p < 0.05). No statistical correlation was found between the knowledge items score of DPs and their behavior (r = 0.18; p = 0.762), attitude (r = 0.04; p = 0.594) and self-rated knowledge (r = 0.42; p = 0.854).ConclusionDental practitioners showed adequate knowledge regarding PDT and its use in dentistry. However, expertise with regards to handling and training is warranted so that DPs could use PDT in their dental practice.     

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study

BackgroundPhotodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma.MethodsAn MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660 nm) at different power densities (1.25–180 J/cm²), the photosensitizer methylene blue (MB) at concentrations of 0.39–100 μM, PDT (12.5 μM MB and laser power densities from 1.25 to 180 J/cm²), and PDT (12.5 μM MB and a laser density of 120 J/cm²) plus ERL (1 μM).ResultsThe laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone.ConclusionsThe sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.     

Endobronchial photodynamic therapy under fluorescence control: Photodynamic theranostics

BackgroundPhotodynamic therapy (PDT) has several advantages. However, one of the disadvantages is its inability to be individualized according to biological characteristics of malignant tumors. The objective of this study was to investigate a strategy for individualized endobronchial PDT in the treatment of centrally located non-small cell lung cancer.MethodsNew approach suggests taking fluorescence-based measurements of chlorine E6 photosensitizer (PS) accumulation in the malignant tumor tissue, and assess PS consumption rate during PDT. Two randomized groups of 45 patients took part in the comparative study of standard PDT procedure, 662 nm, pulse-periodic mode, therapeutic light (reference group – RG) versus the investigated individualized approach under fluorescence control after irradiation with violet light, 408 nm, diagnostic light (study group – SG). The PDT-treatment parameters and results of follow-up bronchoscopy were compared between the groups.Results43 (96%) of 45 patients in SG demonstrated intense fluorescence in the area of the tracheal/bronchial tumor stenosis. 4 (9%) of 45 patients (SG) demonstrated fluorescence of mucosa areas distant from the main tumor lesion after violet light irradiation. Mean fluence during the whole PDT procedure was 95 ± 20 J/cm² (range 60–130 J/cm²), which was significantly lower than in RG (p = 0.01). Total exposure time was significantly lower in SG (365 ± 65 s), compared with RG (690 ± 65 s), P = 0.001. According to the follow-up bronchoscopy the difference in the PDT-treatment results between the groups is statistically insignificant.ConclusionsThe investigated strategy suggests using fluorescence control of the efficacy of PDT-treatment (photodynamic theranostics) to optimize and individualize the PDT procedure.     

Efficacy of high-dose-rate interstitial brachytherapy in patients with oral tongue carcinoma

PurposeTo evaluate the results of high-dose-rate (HDR)-interstitial brachytherapy (ISBT) in oral tongue carcinomas.Methods and MaterialsBetween September 1999 and August 2007, 50 patients were treated for oral tongue carcinoma with HDR-ISBT. The patient's mean age was 58 years. Forty-two patients were in T1–2 stage and 8 patients were in T3 stage; 16 patients were in N+ stage and 34 patients in N0 stage. Exclusive ISBT was given to 17 patients (34%) in T1–2 N0 stage and complementary to external beam radiotherapy (EBRT) to 33 patients (66%). A perioperative technique was performed on 14 patients. The median total dose was 44 Gy when HDR was used alone (4 Gy per fraction) and 18 Gy when complementary to 50 Gy EBRT (3 Gy per fraction).ResultsThe median followup was 44 months. Actuarial disease-free survival rates at 3 and 5 years were 81% and 74%, respectively. Local failure developed in 7 patients. Actuarial local control (LC) rates were 87% and 79% at 3 and 5 years in T1–2 stage 94.5% and 91% and T3 stage 43% and 43% (with salvage surgery). Exclusive HDR cases showed LC in 100% of the cases, and the combined group (EBRT + HDR) showed LC in 80% and 69% of the cases at 3 and 5 years (p = 0.044). Soft-tissue necrosis developed in 16% and bone necrosis in 4% of the cases.ConclusionsHDR brachytherapy is an effective method for the treatment of oral tongue carcinoma in low-risk cases. Doses per fraction between 3 and 4 Gy yield LC and complication rates similar to low-dose rate. The perioperative technique promises encouraging results.     

Photodynamic therapy in oral potentially malignant disorders—Critical literature review of existing protocols

IntroductionOral cancer is a serious public health issue. Apart from its high rate of prevalence, incidence and mortality, it can often result in more complex and expensive treatment when diagnosed late. Potentially malignant disorders (PMDs) can precede oral cancer, and are usually treated by surgical excision. However, in many cases patients are elderly and multiple interventions may be required. Photodynamic therapy (PDT) is a simple alternative, which has been successfully used in the treatment of oral PMDs.ObjectiveDue to the lack of standardization regarding photosensitizers (PTSs), types of irradiation, and methods of application, the objective of this study was to analyze existing PDT protocols in an attempt to identify the one that demonstrates greater efficiency, reliability and feasibility in the treatment of oral PMDs for both researchers and clinicians.MethodsOriginal clinical studies published only in English between 1993 and 2016 were searched in Pubmed/Medline database using the following keywords: photodynamic therapy; oral potentially malignant disorder; oral premalignant lesions. Review articles; experimental studies; case-reports; commentaries; and letters to the Editor were excluded from the selection.Results and conclusionBased on the 16 studies selected, the topical 5-ALA-20% PTS, associated to a LED light applied for 15 min with a 7-day interval between sessions emerged as the most frequently used PDT protocol, with satisfactory results. Due to its low rate of side effects, this PDT protocol presents good potential for the treatment of oral PMDs. Further clinical studies are required to ascertain its long-term validity in preventing oral cancer.     

Photodynamic therapy with high-power LED mediated by erythrosine eliminates Enterococcus faecalis in planktonic forms

BackgroundThe failure of endodontic treatment is linked to the presence of microorganisms, particularly Enterococcus faecalis, in the root canals. This study evaluated the effectiveness of photodynamic therapy (PDT) using erythrosine irradiated by a high-power curing light on a planktonic suspension culture of E. faecalis.MethodsBacterial suspensions of E. faecalis were adjusted and then mixed in a 1:1 proportion, in triplicate, in treatment groups by varying the length of irradiation time (120 and 240 s) and the molarity of the erythrosine (5 and 10 μM). In order to verify the post-treatment bactericidal effect, a count of the viable bacteria was performed (CFU mL⁻¹) and transformed into Log10 CFU. The one-way ANOVA with Tukey post-hoc test was applied to check for differences between the groups.ResultsThe bacteria were completely eradicated in the groups that used PDT with 5 μM 240 s, 10 μM 120 s and 10 μM 240 s (p ≪ 0.001). The effect of the PDT 5 μM 120 s group was significant (p ≪ 0.05) in comparison with the groups using only light or only erythrosine. Positive control (exposure to 2.5% NaClO for 120 and 240 s) completely eradicated E. faecalis. The negative control (PBS) did not alter the quantities of E. faecalis CFU with 9.605 Log10 CFU at 120 s and 9.621 Log10 CFU at 240 s.ConclusionPDT with erythrosine in a concentration of 10 μM and high-power LED is capable of totally eliminating E. faecalis in planktonic suspension.     

5-Aminolevulinic acid-based photodynamic therapy of chordoma: In vitro experiments on a human tumor cell line

BackgroundChordomas are very rare tumors of the skull base and the sacrum. They show infiltrating and destructive growth and are known to be chemo- and radio-resistant. After surgical resection, the recurrence rate is high and overall survival limited. As current adjuvant treatments are ineffective, new treatment concepts are urgently needed. 5-aminolevulinic acid-based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. However, it is unknown so far, whether chordomas accumulate protoporphyrin IX (PPIX) after application of 5-ALA and whether they are sensitive to subsequent 5-ALA based PDT.MethodsThe immortalized human chordoma cells U-CH2 were used as in vitro model. After incubation for 4 h or 6 h with different 5-ALA concentrations, PPIX accumulation was determined by flow cytometry. To assess sensitivity to PDT, chordoma cells were incubated at 30.000 cells/well (high cell density) or 15.000 cells/well (low cell density) with graded doses of 5-ALA (0–50 μg/ml) in 96-well plates and subsequently exposed to laser light of 635 nm wavelength (18.75 J/cm²). Cell survival was measured 24 h after exposure to laser light using the WST-1 assay.ResultsU-CH2 cells dose-dependently accumulated PPIX (ANOVA; p < 0.0001). PPIX fluorescence was significantly higher, when cells were incubated with 5-ALA for 6 h compared to 4 h at higher 5-ALA concentrations (ANOVA/Bonferroni; p ≤ 0.05 for ≥ 30 μg/ml 5-ALA). For both cell densities, a 5-ALA dose-dependent decline in viability was observed (ANOVA; p < 0.0001). Viability was significantly lower at higher 5-ALA concentrations, when 30.000 cells/wells were treated compared to 15.000 cells/well (ANOVA/Bonferroni; p ≤ 0.001 for ≥ 30 μg/ml 5-ALA). LD50 was 30.25 μg/ml 5-ALA.ConclusionThe human UCH-2 cell line was a very useful in vitro model to study different effects of 5-ALA based PDT. For the first time, it could be shown that human chordoma cells may be destroyed by 5-ALA/PDT.     

Clinical efficacy of photodynamic therapy adjunctive to scaling and root planing in the treatment of chronic periodontitis: A systematic review and meta-analysis

PurposeTo evaluate the clinical efficacy of photodynamic therapy (PDT) adjunctive to scaling and root planing (SRP) in patients with untreated chronic periodontitis based on up-to-date evidence.MethodsMEDLINE and the Cochrane Library were systematically searched to identify eligible randomized controlled trials (RCTs), supplemented by a manual literature search. Mean differences (MD) and the corresponding 95% confidence intervals (CI) of probing depth (PD) reduction and clinical attachment level (CAL) gain were synthesized. The I² test and Q statistics were used to determine the inter-study heterogeneity. Subgroup analysis based on smoking status was performed.ResultsEleven RCTs with a total of 243 subjects were included. Significant improvement in PD reduction (MD = 0.13, CI:0.02–0.24, p = 0.02) and marginal significant improvement in CAL gain (MD = 0.18, CI:−0.005–0.363, p = 0.056) were observed in favor of SRP+PDT at 3 months. When evaluated at 6 months after baseline, the association of PDT with SRP resulted in a significant benefit in PD reduction (MD = 0.40, CI:0.05–0.74, p = 0.03), but not in CAL gain (MD = 0.37, CI:−0.18–0.93, p = 0.18). Subgroup analysis revealed that the combined therapy produced no significant improvements in PD and CAL at neither 3 months nor 6 months for studies with smokers. No treatment-related adverse events or side effects had been reported by the included studies.ConclusionsPooled analysis suggests a short-term benefit of PDT as an adjunct to SRP in clinical outcome variables. However, evidence regarding its long-term efficacy is still insufficient and no significant effect has been confirmed in terms of CAL gain at 6 months. Future clinical trials of high methodological quality are needed to establish the optimal combination of photosensitizer and laser configuration.     

Does supplemental photodynamic therapy optimize the disinfection of bacteria and endotoxins in one-visit and two-visit root canal therapy? A randomized clinical trial

AimTo evaluate the effectiveness of supplemental photodynamic therapy (PDT) in optimizing the removal of bacteria and endotoxins from primarily infected root canals after one-visit and two-visit treatments.MethodologyTwenty-four primarily infected root canals with apical periodontitis were selected and randomly divided into one-visit (n = 12) and two-visit treatment groups (n = 12). Chemo-mechanical preparation (CMP) was performed by using the single-file reciprocating technique + 2.5% NaOCL and a final rinse with 17% EDTA. The photosensitizer agent (methylene blue 0.1 mg/mL) was applied to root canals for 60 s before application of laser with a potency of 60 mW and energy density of 129 J/cm² for 120 s after CMP in the one-visit treatment and after 14-day inter-appointment medication with Ca(OH)₂ + Saline solution (SSL) in the two-visit treatment. Samples were collected before and after root canal procedures. Endotoxins were quantified by chromogenic limulus amebocyte lysate assay. Culture techniques were used to determine bacterial colony-forming unit counts.ResultsBacteria and endotoxins were detected in 100% of the initial samples, with median values of 1.97 × 10⁵ CFU/mL and 24.983 EU/mL, respectively. The CMP using single-file reciprocating technique was effective in the reduction of bacteria and endotoxins (All, p < 0.05). The supplemental PDT was effective in reducing bacterial load in the one-visit (p < 0.05) but not in the two-visit treatment after use of Ca(OH)₂ medication for 14 days (p > 0.05). In the two-visit group, after 14 days of inter-appointment medication with Ca(OH)₂, a significant reduction in the median levels of endotoxins was found in comparison to CMP alone (from 1.041 to 0.094 EU/mL) (p < 0.05). Despite the type of treatment, the supplemental PDT was not effective against endotoxins (p > 0.05).ConclusionsThe photodynamic therapy optimized the disinfection of bacteria from root canals in one-visit but not for two visit treatment modality with the accomplishment of calcium hydroxide medication. Despite the type of treatment, the supplemental PDT was not effective against endotoxins.     

A randomized split-face clinical trial analyzing daylight photodynamic therapy with methyl aminolaevulinate vs ingenol mebutate gel for the treatment of multiple actinic keratoses of the face and the scalp

IntroductionDaylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs).The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB.MethodsTwo symmetrical contralateral areas of 25 cm², harboring a similar (5–10) number of AKs, were selected and randomly assigned either to a 3 days’ IMB treatment cycle or to a single session of dlPDT. The day after the local skin reaction (LSR) score was registered. Patients’ scored pain (assessed through VAS method) after the treatment, and time needed for wound closure, were subsequently registered. After 90 days, the complete remission (CR) rate recorded for both single lesions and patients, the cosmetic outcome and the patients’ preference, were assessed.Results22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55 ± 1.82 with IMB and 2.05 ± 0.72 with dlPDT (p < 0.01). The mean LSR score was 9.91 ± 4.24 and 4.59 ± 4.03 (p < 0.01), respectively. The mean days necessary for wound closure were 9.45 ± 3.51 and 4.36 ± 1.18 days (p < 0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p = NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment.ConclusionsA 3 days’ treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients’ preference.     

In vitro evaluation of adhesion/proliferation of human gingival fibroblasts on demineralized root surfaces by toluidine blue O in antimicrobial photodynamic therapy

BackgroundAntimicrobial photodynamic therapy (aPDT) in Dentistry has important effects as bacterial destruction in areas with periodontal disease. Some dyes applied in aPDT could present low pH and, consequently, result in tooth demineralization. This study evaluated demineralization produced by aPDT with toluidine blue O (TBO) at low pH and analyzed adhesion/proliferation of human gingival fibroblasts (HGF).MethodsIn the 1st phase, bovine enamel and root dentin fragments received 2 treatments: PDT4 group (TBO–100 μg/ml—pH 4–60 s) plus laser (660 nm, 45 J/cm², 1.08 J, 30 mW, 30 s, spot 0.024 cm², 1.25 W/cm², sweeping, non-contact) and CA group (citric acid plus tetracycline—pH 1–180 s). Surface hardness loss and tooth wear were statistically analyzed (Student’s t test, ANOVA/Tukey, p < 0.05). In the 2nd phase, human dentin fragments were divided in C (control group—scaling and root planing), PDT4 and CA. HGF (10⁴, 5th passage) were cultured on these fragments for 24, 48 and 72 h and counted in scanning electron microscopy photographs. Number of HGF was analyzed using repeated-measures ANOVA and Tukey (p < 0.05).ResultsPercentage of surface hardness loss was similar in dentin for PDT4 (71.5%) and CA (76.1%) (p > 0.05) and higher in enamel for CA (68.0%) compared to PDT4 (34.1%) (p < 0.05). In respect to wear, no difference was found between PDT4 (dentin: 12.58 μm, enamel: 12.19 μm respectively) and CA (dentin: 11.74 μm and enamel: 11.03 μm) (p > 0.05). Number of HGF was higher after 72 h in CA group (2.66, p < 0.05) compared to PDT4 (2.2) and C (1.33).ConclusionPDT4 is not as aggressive as CA for enamel. However, dentin demineralized promoted by PDT4 does not stimulate HGF adhesion and proliferation as CA.     

Evaluation of photodynamic therapy on fibroblast viability and cytokine production

BackgroundThe aim of this study was to evaluate the effects of photodynamic therapy with curcumin (PDT) comparatively to 5% sodium hypochlorite (NaOCl) and saline solution on cell viability and cytokine (IL-1β and IL-6) production by mouse fibroblasts.MethodsSixty seconds of pre-irradiation time with curcumin 500 mg/L and Led wavelength (λ) 480 nm, 72 J cm², for 300 s was used for PDT. Solutions were diluted in culture medium DMEM (1 × 10⁴ cells) and placed into 24-well cell culture plates with mouse fibroblasts L-929. Culture medium was used as control. After 6, 24 and 48 h, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) was used to evaluate the cell viability and the supernatant was collected for cytokine evaluation using enzyme-linked immunosorbent assay (ELISA). The results were statistically analyzed by ANOVA and BonFerroni correction (p < 0.05) for MTT and Kruskal–Wallis test and Dunn (p < 0.05) for ELISA.ResultsPDT and saline solution presented low cytotoxic effect similar to the control group (p > 0.05) while 5% NaOCl was more cytotoxic than PDT (p < 0.05) in all periods of time. All materials similarly expressed IL-1β and IL-6 regardless to the experimental period (p < 0.05).ConclusionsPDT with curcumin was not cytotoxic to L929 fibroblasts differently from 5% NaOCl. In all groups occurred similar expression of IL-1β and IL-6.