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1.
Oral Dis ; 30(2): 504-517, 2024 Mar.
Article in English | MEDLINE | ID: mdl-36648368

ABSTRACT

OBJECTIVES: To investigate the role of oral lichen planus (OLP) on the long-term prognosis of oral epithelial dysplasia (OED). METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.


Subject(s)
Carcinoma, Squamous Cell , Lichen Planus, Oral , Mouth Neoplasms , Humans , Lichen Planus, Oral/pathology , Mouth Neoplasms/pathology , Retrospective Studies , Cohort Studies , Carcinoma, Squamous Cell/pathology , Hyperplasia , Prognosis
2.
Int Angiol ; 42(5): 448-456, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37943292

ABSTRACT

BACKGROUND: Arteriovenous malformations (AVMs) are developmental defects in the vascular system with abnormal connections between arteries and veins. A minority of AVMs are characterized by aggressive growth and continue to proliferate despite maximal surgical and interventional therapy. We report our outcomes with the use of thalidomide as the only UK specialist center adopting this novel approach for the management of AVMs refractory to conventional therapy. METHODS: This was a retrospective case series which included only complex and proliferative AVM lesions (Schobinger grade III and IV). All patients prescribed thalidomide on a compassionate basis between September 2006 and August 2022 after attempts at embolosclerotherapy without satisfactory response were reviewed. RESULTS: Eleven patients were included in our study. The median total duration of thalidomide use was 10 months. Two thirds of patients with pain (six of nine) reported an improvement, three quarters reported a reduction in swelling (six of eight) and all who presented with bleeding reported improvement in overall volume or frequency (four of four). Over the study period, 45% achieved a non-proliferative state with no further target vessel demonstrable on angiography. Mild, tolerable side effects such as fatigue were common (73%). There was only one major adverse reaction (neutropenia) necessitating cessation of therapy. CONCLUSIONS: We can conclude that thalidomide is able to reduce the symptom burden for patients with complex and proliferative AVMs that were refractory to established treatment modalities. Adverse effects are common, but the benefit achieved from taking thalidomide in otherwise treatment resistant cases outweighs the risks, most of which are manageable.


Subject(s)
Embolization, Therapeutic , Intracranial Arteriovenous Malformations , Radiosurgery , Humans , Retrospective Studies , Thalidomide/adverse effects , Intracranial Arteriovenous Malformations/diagnosis , Intracranial Arteriovenous Malformations/etiology , Intracranial Arteriovenous Malformations/surgery , Treatment Outcome , Radiosurgery/adverse effects , Embolization, Therapeutic/adverse effects
3.
J Biomed Opt ; 28(8): 082809, 2023 08.
Article in English | MEDLINE | ID: mdl-37483565

ABSTRACT

Significance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed. Aim: Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL). Approach: A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions (<2 cm diameter and <5 mm depth) were systemically (in oral solution) administered three doses of 20 mg/kg ALA (total 60 mg/kg). Lesion site PpIX and auto-FL were imaged using the multichannel FL and polarized white-light oral cancer imaging probe before/after ALA administration and after light delivery (fractionated, total 100 J/cm2 of 635 nm red LED light). Results: The handheld device was conducive for access to lesion site images in the oral cavity. Segmentation of ratiometric images in which PpIX FL is mapped relative to auto-FL enabled improved demarcation of lesion boundaries relative to PpIX alone. A relative FL (R-value) threshold of 1.4 was found to segment lesion site PpIX production among the patients with mild to severe dysplasia malignancy. The segmented lesion size is well correlated with ultrasound findings. Lesions for which R-value was >1.65 at the time of treatment were associated with successful outcomes. Conclusion: These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Photochemotherapy , Humans , Aminolevulinic Acid/therapeutic use , Smartphone , Mouth Neoplasms/pathology , Photochemotherapy/methods , Protoporphyrins/metabolism , Photosensitizing Agents/therapeutic use
4.
J Biophotonics ; 16(7): e202300046, 2023 07.
Article in English | MEDLINE | ID: mdl-37017292

ABSTRACT

Phototherapy incorporating photobiomodulation therapy and antimicrobial photodynamic therapy has been utilised as antioxidants in symptomatic oral lichen planus (OLP) management; however, its role of intervention remains controversial. The aim of this systematic review of CRD42021227788 PROSPERO (an international prospective register of systematic reviews in health and social care) registration number was to oversee and determine phototherapy efficacy in patients with symptomatic OLP, identifying and bridging the literature gaps by proposing recommendations for future studies. A search strategy was developed in consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Various electronic databases were exercised to search for randomised controlled clinical trials (RCTs). Several search engines were employed to analyse a total of 177 studies of which nine included. A wide range of utilised laser and light-emitted diode wavelengths between 630 and 808 nm and irradiance ranged between 10 and 13 mW/cm2 were noted. 67% of studies reported a high risk of bias and a high heterogeneity obtained from numerical data for quantitative analysis, therefore meta-analysis was impossible to conduct. Despite inconsistency and diversity in phototherapy parameters, treatment protocols, photosensitiser (type, concentration and method of application) and outcome assessment tools, the majority of the studies showed positive results compared with standard care treatments. Hence, a necessity to perform well-designed RCTs with robust methodology is warranted, after acknowledging the current drawbacks and addressing the suggested recommendations highlighted in our review. Moreover, advanced knowledge in understanding further phototherapy-antioxidants molecular mechanistic in symptomatic OLP is required.


Subject(s)
Lichen Planus, Oral , Low-Level Light Therapy , Photochemotherapy , Humans , Antioxidants , Lichen Planus, Oral/radiotherapy , Lichen Planus, Oral/drug therapy , Photochemotherapy/methods , Phototherapy , Randomized Controlled Trials as Topic
5.
Photodiagnosis Photodyn Ther ; 39: 103019, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35850459

ABSTRACT

Ulcers in the oral mucosa is a relatively common, although challenging, entity in oral medicine, as it can arise due to a wide range of traumatic, infective, autoimmune, and neoplastic disorders. Although histopathology of lesional and peri­lesional tissues remains the gold standard for persistent oral breaching, optical coherence tomography (OCT) has been recently suggested as a potential ally to enhance the early or non-invasive diagnosis of likely causation. The aim of the present study was to provide an in-vivo OCT analysis and description from a sample of 70 patients affected by traumatic or neoplastic-related ulcers, located on the buccal mucosa, tongue or gingiva, and compare the OCT data with those of 20 patients with healthy oral mucosa. OCT dynamic scans revealed clear distinction of epithelial layer (EP), lamina propria (LP) of healthy buccal mucosa, gingiva, and tongue as well as allowing observation of the keratin layer in gingiva, and the subepithelial vascularization of each site. Traumatic lesions had an EP of reduced in thickness, with an irregular, if not disrupted surface. Interestingly, LP seemed to preserve its reflectiveness and vascularization only in the traumatic lesions. Among neoplastic lesions, regardless their site of onset, both EP integrity/homogeneity, and LP reflectiveness/vascularization were lost and unrecognizable when compared to their healthy counterparts. OCT scanning allowed some differentiation between traumatic and malignant ulcers and thus may a useful and non-invasive means of determining the need and/or urgency of histopathological examination of oral lesions.


Subject(s)
Oral Ulcer , Photochemotherapy , Humans , Mouth Mucosa/diagnostic imaging , Mouth Mucosa/pathology , Oral Ulcer/pathology , Photochemotherapy/methods , Tomography, Optical Coherence/methods , Ulcer/pathology
6.
Photodiagnosis Photodyn Ther ; 38: 102843, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35367616

ABSTRACT

BACKGROUND: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery. METHODS: 30 patients with T1N0M0 buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps. Tumour limits were defined by external ultrasound (US), white light photos and increased tumour fluorescence after oral administration of the photosensitising agent ALA (60 mg/kg, divided doses), monitored by a smartphone fluorescence imaging device. 100 J/cm2 LED light (635 nm peak) was delivered followed by repeat fluorescence to assess photobleaching. US and biopsy were repeated after 7-17 days. This trial is registered with ClinicalTrials.gov, NCT03638622, and the study has been completed. FINDINGS: There were no significant complications or discomfort. No sedation was required. No residual disease was detected in 22 out of 30 patients who completed the study (26 of 34 lesions, 76% complete tumour response, 50 weeks median follow-up) with up to 7.2 mm depth of necrosis. Treatment failures were attributed to large tumour size and/or inadequate light delivery (documented by limited photobleaching). Moderately differentiated lesions were more responsive than well-differentiated cancers. INTERPRETATION: This simple and low-cost adaptation of fluorescenceguided PDT is effective for treatment of early-stage malignant oral lesions and may have implications in global health.


Subject(s)
Mouth Neoplasms , Photochemotherapy , Aminolevulinic Acid/therapeutic use , Humans , India , Mouth Neoplasms/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use
7.
Photodiagnosis Photodyn Ther ; 38: 102800, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35283295

ABSTRACT

INTRODUCTION: Healthcare related quality of life (QoL) is defined as the impact one's level of health and wellbeing has on a number of domains, including physical, mental, spiritual and social functions. Photodynamic therapy (PDT), a cancer treatment modality, is increasingly used to treat or palliate head and neck pathologies. Due to the complex nature of this area of the body, both the pathology and the treatment of it can severely affect the quality of life. Thus far, no questionnaire has been developed which focuses on quality-of-life post-PDT of head and neck pathologies. PATIENTS AND METHODS: We have developed the University College London Quality of Life Questionnaire for Patients undergoing PDT in the Head and Neck, using meta-tetra(hydroxyphenyl)chlorin (mTHPC) as the photosensitiser. This was modified from the University of Washington quality of life (UW-QOL) questionnaire. Thirty-eight patients who received mTHPC-PDT for various head and neck pathologies completed the questionnaire, with a mean follow-up of 56 days. RESULTS: All patients reported improved QoL following mTHPC-PDT. The main problem that was reported was post-PDT pain, which is a common side effect. Visual symptoms, breathing, speaking and swallowing problems improved significantly in the 4th week following treatment and significant improvement in activities of daily living, social life, mood and anxiety were reported in the subsequent weeks. CONCLUSIONS: mTHPC-PDT confers improvement in QoL score in selected head and neck cancer patients with figures comparable to other treatment modalities. This exploratory study demonstrated patterns of QoL outcome. Further work needs to be done for survey validation and inclusion of a larger cohort which will allow optimal sub-group analysis and help guide further interventions.


Subject(s)
Head and Neck Neoplasms , Photochemotherapy , Activities of Daily Living , Head and Neck Neoplasms/drug therapy , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Quality of Life
8.
Photodiagnosis Photodyn Ther ; 36: 102520, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34496299

ABSTRACT

BACKGROUND: The primary aim of this prospective study is to demonstrate the technical feasibility of OCT to map real tumor margins and to monitor skin changes that occurred post- PDT. Moreover, to optimize PDT efficacy based on the relationship between measured OCT features and treatment outcome. MATERIAL AND METHODS: A series of 12 patients with overall 18 facial skin lesions were investigated by OCT before surface illumination by PDT to determine tumor free margins. Monitoring of the healing process was undertaken at 3, 6 and 12 months post-PDT. Parameters measured by the in vivo OCT during healing phase were the organization of skin layer and the degree skin fibroses for the active center and peripheral transit zone of the treated lesion. Clinical and aesthetics assessment was carried out at 12-month post-PDT. RESULTS: Distinct microstructural differences between normal skin, pre-cancer, cancer, and the transition zone between the two tissues were observed on OCT images. In the subsequent healing phase, OCT demonstrate marked delineation and organization of skin layer at late stage of healing. Early features showing bizarre non-homogenous disorganized layering (scab) but afterwards, OCT was able to differentiate between different histological layers. One lesion demonstrated clinical healing by fibrosis (scar) without sign of recurrence. Another lesion demonstrated skin erythema. Only one lesion did not response to treatment despite margins clearance. The CR rate was 95% at the end of the study. The cosmetic effect was "excellent" in 89% of the patients. CONCLUSIONS: This feasibility study lays the groundwork for using OCT as a real-time, noninvasive monitoring device for PDT in patients with skin cancer.


Subject(s)
Photochemotherapy , Skin Neoplasms , Humans , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Prospective Studies , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/drug therapy , Tomography, Optical Coherence
9.
Photodiagnosis Photodyn Ther ; 36: 102528, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34509683

ABSTRACT

A 77-year-old Caucasian male was diagnosed with squamous cell cancer of the right ear. The patient elected to take part in the first-in-man phase I TPCS2a based bleomycin photochemical internalization (PCI). On Day 0, The patient received the photosensitiser [Amphinex (TPCS2a)], by slow intravenous injection. Four days later, surface illumination based (PCI) was implemented 3 h after the slow infusion of Bleomycin. Four weeks following the infusion of the photosensitiser, the cancerous area turned into black rigid mass with clear demarcation from the macroscopically normal skin. The size of the treated area has been substantially reduced. Histopathologic assessment of the excised necrotic mass revealed no viable tumour and the excised margins (PCI-treated margins) were tumour-free. This case was a clear indication that PCI is a clinically relevant technique that has potential in the treatment of such cancers to avoid radical intervention.


Subject(s)
Carcinoma, Squamous Cell , Photochemotherapy , Aged , Bleomycin , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Humans , Male , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use
10.
Photodiagnosis Photodyn Ther ; 36: 102493, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34419675

ABSTRACT

BACKGROUND: Skin cancer continues to be the most common cancer in the Caucasian population. Over the past two decades, researchers around the world started assessing the possibility of diagnosing tissue pathologies by using optical systems. In this study, we aimed to use in vivo optical coherence tomography (OCT) technology to describe the morphologic features of normal and pathologic skin conditions. MATERIALS AND METHODS: In this study, 72 patients with suspected skin pre-cancer/cancer were recruited. The lesions were subjected to in vivo OCT scanning using compact size probe. The main scanned areas were the centre of the lesion, periphery of the lesion and control reading at least 2cm from the lesion periphery but within the same dermatomal distribution. Following assessment, each lesion was surgically excised. All acquired OCT images were correlated with the corresponding histopathology images to ensure an accurate diagnosis and appropriate co-localisation of abnormal lesion on both OCT image and pathology slide. This was achieved in every resected lesion. RESULTS: Histopathological analysis revealed that of the 96 macroscopically suspicious scanned lesions 26 were actinic keratosis (AK), 51 were basal cell carcinoma (BCC) and 19 were cutaneous squamous cell carcinoma (SCC). Different layers of healthy skin can be distinguished with clear demarcation between the epidermis and papillary dermis. An increase in epidermal thickness was observed in OCT images in AK that appeared relatively hyperintense. Cutaneous SCC was characterized by hypoechoic signal free spaces within the dermis and damaged of dermal-epidermal junction. BCCs were visualized as hypoechoic structures but showed a mixed echogenicity. Solid nodular BCC appeared as single or multiple areas with no clear arrangement surrounding low-reflectivity lobular structures surrounded. Cystic structures were identifiable by signal-free areas adjacent to healthy skin. Sensitivity and specificity for in vivo OCT in diagnosing these lesions were impressive, based on this small sample size. CONCLUSIONS: OCT have shown that there are qualitative differences in OCT image features of skin with varying degrees of pathology, and between normal and pathological skin. This study indicates that in vivo OCT shows a good promise as a useful optical diagnostic technique in diagnosing skin pathologies.


Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Photochemotherapy , Skin Neoplasms , Carcinoma, Basal Cell/diagnostic imaging , Humans , Photochemotherapy/methods , Photosensitizing Agents , Prospective Studies , Skin Neoplasms/diagnostic imaging , Tomography, Optical Coherence
11.
Photodiagnosis Photodyn Ther ; 34: 102255, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33727132

ABSTRACT

INTRODUCTION: Oral lichen planus (OLP) is a common oral inflammatory condition. Against symptomatic atrophic-erosive OLP, topical steroids, or photobiomodulation (PBM) are deployed. Optical coherence tomography (OCT) provides a real-time, non-invasive, tissue investigation. Aim of this study was to evaluate modifications of OCT pattern in patients with painful atrophic-erosive OLP, before and after treatment with PBM, comparing those results with patients treated with topical steroid. METHODS: Two groups of 20 OLP patients were evaluated. Group A underwent two daily application of 0.05 % clobetasol propionate for 8 weeks; group B was treated with eight weekly PBM sessions using a 980/645 nm diode laser. OCT scans were performed before and after treatment, and six months after end of the proposed protocol. Changes of width of stratified epithelium (EP) and lamina propria (LP) were quantified. RESULTS: After 8-weeks, both groups experienced a significant increase of EP width (p < 0.05), and a significant decrease of LP width (p < 0.05), with Δ-EP in Group A significantly higher than Group B (p = 0.0015); conversely, Δ-LP was not significantly different (p > 0.05). After six months, significant increase of EP width remained only in group B (p = 0.01), with no significant decrease of LP mean width in both groups (p > 0.05). CONCLUSIONS: Increase of EP and decrease of LP might be explained as consequence of clobetasol and PBM ability to promote epithelial healing, and to reduce interface inflammation. When investigated with OCT, clobetasol appears to provide more significant short-term structural changes, whereas PBM might guarantee long-term alterations.


Subject(s)
Lichen Planus, Oral , Photochemotherapy , Administration, Topical , Anti-Inflammatory Agents/therapeutic use , Glucocorticoids/therapeutic use , Humans , Lichen Planus, Oral/drug therapy , Lichen Planus, Oral/therapy , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Tomography, Optical Coherence
12.
Br Dent J ; 229(6): 355-360, 2020 09.
Article in English | MEDLINE | ID: mdl-32978578

ABSTRACT

The rates of oropharyngeal squamous cell carcinoma have continued to rise secondary to the increasing prevalence of the human papillomavirus (HPV). HPV-related disease is typically found in younger patients who do not have the traditional risk factors for malignancy. General dental practitioners (GDPs) often examine patients regularly and may therefore have an opportunity to identify oropharyngeal malignancies at an early stage. However, many GDPs are unfamiliar with oropharyngeal anatomy, pathology and clinical examination. This review summarises the key points in identifying patients with oropharyngeal malignancy who necessitate urgent referral.


Subject(s)
Alphapapillomavirus , Oropharyngeal Neoplasms , Papillomavirus Infections , Dentists , Humans , Oropharyngeal Neoplasms/diagnosis , Oropharyngeal Neoplasms/epidemiology , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Professional Role
13.
J Photochem Photobiol B ; 211: 112009, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32862089

ABSTRACT

Oral lichen planus (OLP) is a common premalignant chronic inflammatory disorder. Optical Coherence Tomography (OCT) provides a real-time, non-invasive, and in-situ optical signature using light of varying wavelengths to examine tissue. Aim of the present study was to assess the possible role of OCT as diagnostic tool for atrophic-erosive OLP by examining OCT scans of healthy buccal mucosa, and comparing their ultrastructural features with those of a buccal mucosa affected by atrophic-erosive OLP, using their histopathological counterparts as the gold standard. Through grayscale (enface scan) and an application in which the vascularization of the tissue is visible (dynamic scan), it was possible to distinguish the healthy from the lichenoid pattern from 20 controls (12 M; 8 F; mean age: 41.32 years) and 20 patients with histologically confirmed atrophic-erosive OLP (7 M; 13 F; mean age: 64.27 years). In detail, mean width of stratified squamous epithelium (EP) and lamina propria (LP) were evaluated. Among controls, EP and LP showed a mean width of 300 (±50) and of 600 (±50) µm respectively; among cases, disruption of membrane basement prevented from any measurement. Furthermore, a differential pattern of EP and LP emerged between the two groups: a light-grayish, hypo-reflective, homogeneous area of EP recurring in controls turned into a hyper-reflective, non-homogeneous area among cases. Dynamic scan showed a differential profile of LP vascularization, varying from a hypo-reflective red area with small blood vessels in the control group, to a hypo/hyper-reflective area, completely overrun by a denser, wider blood flow amid OLP cases. Although histopathological examination remains the gold standard for OLP diagnosis, OCT could be a potentially helpful tool for the clinician and the pathologist, since it allows analysis of the vascularization of the sample without adversely affecting histological processing.


Subject(s)
Lichen Planus, Oral/drug therapy , Mouth Mucosa/diagnostic imaging , Tomography, Optical Coherence/methods , Adult , Biopsy , Female , Humans , Kinetics , Lichen Planus, Oral/pathology , Light , Male , Middle Aged , Mouth Mucosa/physiology , Mouth Mucosa/ultrastructure , Precancerous Conditions/metabolism
14.
J Biomed Opt ; 25(6): 1-10, 2020 04.
Article in English | MEDLINE | ID: mdl-32279466

ABSTRACT

SIGNIFICANCE: India has one of the highest rates of oral cancer incidence in the world, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. Photodynamic therapy (PDT) has emerged as an effective modality with potential for treating early stage disease in resource-limited settings, while photosensitizer fluorescence can be leveraged for treatment guidance. AIM: Our aim was to assess the capability of a simple smartphone-based device for imaging 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence for treatment guidance and monitoring as part of an ongoing clinical study evaluating low-cost technology for ALA-based PDT treatment of early oral cancer. APPROACH: A total of 29 subjects with <2 cm diameter moderately/well-differentiated microinvasive ( < 5 mm depth) oral squamous cell carcinoma lesions (33 lesions total, mean area ∼1.23 cm2) were administered 60 mg / kg ALA in oral solution and imaged before and after delivery of 100 J / cm2 total light dose to the lesion surface. Smartphone-based fluorescence and white light (WL) images were analyzed and compared with ultrasound (US) imaging of the same lesions. RESULTS: We present a comparative analysis of pre- and post-treatment fluorescence, WL, and US images of oral lesions. There was no significant difference in the distribution of lesion widths measured by fluorescence and US (mean widths of 14.5 and 15.3 mm, respectively) and linear regression shows good agreement (R2 = 0.91). In general, PpIX fluorescence images obtained prior to therapeutic light delivery are able to resolve lesion margins while dramatic photobleaching (∼42 % ) is visible post-treatment. Segmentation of the photobleached area confirms the boundaries of the irradiated zone. CONCLUSIONS: A simple smartphone-based approach for imaging oral lesions is shown to agree in most cases with US, suggesting that this approach may be a useful tool to aid in PDT treatment guidance and monitoring photobleaching as part of a low-cost platform for intraoral PDT.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Photochemotherapy , Aminolevulinic Acid , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/drug therapy , Humans , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/drug therapy , Optical Imaging , Photosensitizing Agents/therapeutic use , Protoporphyrins , Smartphone
15.
J Clin Med ; 9(2)2020 Feb 14.
Article in English | MEDLINE | ID: mdl-32075165

ABSTRACT

Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin. This new intervention has also been found appealing for intracellular delivery of drugs incorporated into nanocarriers and for cancer vaccination. PCI is currently being evaluated in clinical trials. Data from the first-in-human phase I clinical trial as well as an update on the development of the PCI technology towards clinical practice is presented here.

16.
Photochem Photobiol ; 96(3): 680-683, 2020 05.
Article in English | MEDLINE | ID: mdl-31901218

ABSTRACT

Photochemical internalization (PCI) depends on the delivery of sublethal photodynamic reaction to facilitate the work of a chemotherapeutic agent. We discuss our experience in managing a patient with extensive squamous cell carcinoma of the right face and scalp under the TPCS2a -based bleomycin PCI treatment protocol. In this case, an 84-year-old Caucasian received 0.25 mg kg-1 of TPCS2a (Amphinex® , PCI Biotech AS, Oslo, Norway). Surface illumination photochemical internalization was carried out after 4 days, which was preceded by the chemotherapeutic agent infusion (Bleomycin). After one week from the illumination time, tissue necrosis was evident and tumor shrinkage was most noticeable at day 14 postillumination. Follow-up at 6 weeks continued to show tissue healing and regeneration with no clinical evidence of recurrence. Multiple surgical biopsies were taken at 1 and 3 months postillumination and found to be tumor free. PCI's depth of effect has been very significant with negligible damage to the collateral tissues. This technology has a role in interventional oncology especially when managing challenging cases.


Subject(s)
Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Skin Neoplasms/drug therapy , Squamous Cell Carcinoma of Head and Neck/drug therapy , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/therapeutic use , Bleomycin/therapeutic use , Face , Humans , Male , Remission Induction , Scalp , Treatment Outcome
17.
Skin Res Technol ; 26(2): 153-162, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31544983

ABSTRACT

BACKGROUND: In this immediate ex vivo study, we aimed to identify the structures of normal and pathological facial skin using optical coherence tomography (OCT) and compared them to the gold standard histopathology. MATERIAL AND METHODS: A total of 53 patients, with 57 suspicious facial lesions, participated in this study. A set of variables have been highlighted by the pathologist to represent the minimum unique features that could be used to diagnose a skin pathology have been included in a checklist. One pathologist used this checklist while examining the histopathology slides and one clinician while examining the OCT images. The data from both checklists have been reviewed and compared. RESULTS: Optical coherence tomography's overall accuracy in diagnosing AK was 83%. Best accuracy was achieved in diagnosing BCC and was 97%, while it was 85% for cutaneous SCC. OCT failed to diagnose LM with an accuracy of 33.3% based on the two parameters of the pathology checklist, while it was 81% for malignant melanoma. CONCLUSION: This study proved the success of OCT in identifying structural changes in normal and pathological facial skin. Further studies to prove its usefulness in vivo are recommended.


Subject(s)
Face , Skin Neoplasms , Skin , Tomography, Optical Coherence/methods , Adult , Aged , Aged, 80 and over , Biopsy , Face/diagnostic imaging , Face/pathology , Female , Histocytochemistry , Humans , Male , Middle Aged , Reproducibility of Results , Skin/diagnostic imaging , Skin/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathology
18.
Skin Res Technol ; 26(3): 338-342, 2020 May.
Article in English | MEDLINE | ID: mdl-31777106

ABSTRACT

INTRODUCTION: Photodynamic therapy (PDT) is a relatively new method of treating skin cancers. This prospective study highlights the use of PDT in the management of basal cell carcinomas (BCCs) and T1N0 cutaneous squamous cell carcinomas (SCCs) involving the periorbital area. MATERIALS AND METHODS: Surface illumination PDT was offered under local anaesthesia. mTHPC was administered intravenously. A single-channel 652 nm diode laser was used for illumination, and light was delivered at 20 J/cm2 per site. Lesion response evaluation was carried out according to response evaluation criteria in solid tumours (RECIST). RESULTS: After the first round of treatment, all cutaneous T1N0 SCC patients had complete response (CR) and continued to be in remission until last clinic review. For BCC patients, 12/14 patients had CR. The two remaining patients underwent a second round of treatment and also achieved a CR. All BCC patients were in remission at the last clinic review. Using visual analogue scale (VAS), 15 patients reported that this treatment gave them "excellent" cosmetic outcome (VAS 9-10). CONCLUSION: Photodynamic therapy achieved high efficacy in the treatment of periorbital BCCs and cutaneous SCCs with greatly reduced morbidity and disfigurement.


Subject(s)
Carcinoma, Basal Cell/drug therapy , Carcinoma, Squamous Cell/drug therapy , Mesoporphyrins/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Administration, Intravenous , Adult , Aged , Female , Humans , Male , Mesoporphyrins/administration & dosage , Mesoporphyrins/adverse effects , Middle Aged , Neoplasm Staging/methods , Photochemotherapy/adverse effects , Photochemotherapy/statistics & numerical data , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Prospective Studies , Skin Neoplasms/pathology , Treatment Outcome
20.
Photodiagnosis Photodyn Ther ; 29: 101616, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31811948

ABSTRACT

BACKGROUND: The assessment of cutaneous cancer margins intra-operatively or in the immediate postoperative phase can guide the operator into achieving clear margins. Achieving clear (tumour-free) margins following surgery is an essential factor that can reduce morbidity and disfigurement. The aim of present study was to determine the accuracy of optical coherence tomography in assessing cutaneous cancer margins of the face. MATERIALS AND METHODS: The excised tissue specimens that were examined, in this study, were acquired from 70 patients with 70 facial cancer lesions, with no nodal disease. Forty lesions were basal cell carcinomas (150 margins; 27 tumour positive) and the remaining thirty were cutaneous squamous cell carcinomas (112 margins; 22 tumour positive). These 70 resected lesions were subjected to optical coherence tomography (OCT) in the immediate ex vivo phase to assess each specimen's four margins status (anterior, posterior, medial and lateral). Two reviewers, blinded to the diagnosis, carried out the assessment of the acquired OCT images and measured the mean thickness. Intra- and inter-reviewer agreement was also calculated. RESULTS: On OCT, tumour-involved margins displayed sudden change in thickness associated with architectural changes. BCC-involved margins showed homogenous oval nests with dark rim and dark cysts or an empty space below dermo-epidermal junction depending on the sub-type. In the case of cutaneous SCC-involved margins, the DEJ had lost its integrity with/out the presence of small bright clusters in the papillary dermis and damage to the superficial epidermal layers. The mean thickness of the whole epidermal layer of the tumour-free margin was 128 µm, while for the BCC-involved margin 640 µm, and for the cutaneous SCC-involved margin 810 µm. The sensitivity of using OCT in examining BCC-involved margins was 88.9-92.6 % and the specificity was 96.8-98.4 %. For cutaneous SCC-involved margins, the sensitivity was 81.8-91.0 % and the specificity 85.6-91.1 %. There was "strong" inter-reviewer agreement on the BCC-involved margins, while the agreement was "moderate" for the cutaneous SCC-involved margins. CONCLUSION: OCT provides good accuracy in identifying cutaneous cancer margins. This can potentially be used to guide and monitor resection in real-time. Tumour thickness could be measured due to the thin skin of the face, but may be more difficult to measure accurately in thick tumours and/or thick skin areas.


Subject(s)
Carcinoma, Basal Cell , Photochemotherapy , Skin Neoplasms , Carcinoma, Basal Cell/diagnostic imaging , Carcinoma, Basal Cell/surgery , Humans , Margins of Excision , Photochemotherapy/methods , Photosensitizing Agents , Skin Neoplasms/diagnostic imaging , Tomography, Optical Coherence
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