CO2 lasers in the management of potentially malignant and malignant oral disorders

The CO2 laser was invented in 1963 by Kumar Patel. Since the early 1970s, CO2 laser has proved to be an effective method of treatment for patients with several types of oral lesions, including early squamous cell carcinoma. Laser surgery of oral premalignant disorders is an effective tool in a complete management strategy which includes careful clinical follow-up, patient education to eliminate risk factors, reporting and biopsying of suspicious lesions and any other significant lesions. However, in a number of patients, recurrence and progression to malignancy remains a risk. CO2 laser resection has become the preferred treatment for small oral and oropharyngeal carcinomas. Laser resection does not require reconstructive surgery. There is minimal scarring and thus, optimum functional results can be expected. New and improved applications of laser surgery in the treatment of oral and maxillofacial/head and neck disorders are being explored. As more surgeons become experienced in the use of lasers and as our knowledge of the capabilities and advantages of this tool expands, lasers may play a significant role in the management of different pathologies

Structural validation of oral mucosal tissue using optical coherence tomography

Background: Optical coherence tomography (OCT) is a non-invasive optical technology using near-infrared light to produce cross-sectional tissue images with lateral resolution. Objectives: The overall aims of this study was to generate a bank of normative and pathological OCT data of the oral tissues to allow identification of cellular structures of normal and pathological processes with the aim to create a diagnostic algorithm which can be used in the early detection of oral disorders. Material and methods: Seventy-three patients with 78 suspicious oral lesions were referred for further management to the UCLH Head and Neck Centre, London. The entire cohort had their lesions surgically biopsied (incisional or excisional). The immediate ex vivo phase involved scanning the specimens using optical coherence tomography. The specimens were then processed by a histopathologist. Five tissue structures were evaluated as part of this study, including: keratin cell layer, epithelial layer, basement membrane, lamina propria and other microanatomical structures. Two independent assessors (clinician and pathologist trained to use OCT) assessed the OCT images and were asked to comment on the cellular structures and changes involving the five tissue structures in non-blind fashion. Results: Correct identification of the keratin cell layer and its structural changes was achieved in 87% of the cohort; for the epithelial layer it reached 93.5%, and 94% for the basement membrane. Microanatomical structures identification was 64% for blood vessels, 58% for salivary gland ducts and 89% for rete pegs. The agreement was “good” between the clinician and the pathologist. OCT was able to differential normal from pathological tissue and pathological tissue of different entities in this immediate ex vivo study. Unfortunately, OCT provided inadequate cellular and subcellular information to enable the grading of oral premalignant disorders. Conclusion: This study enabled the creation of OCT bank of normal and pathological oral tissues. The pathological changes identified using OCT enabled differentiation between normal and pathological tissues, and identification of different tissue pathologies. Further studies are required to assess the accuracy of OCT in identification of various pathological processes involving the oral tissues

Current practice in the management of frontal sinus fractures

Fractures of the frontal sinus are seen predominantly, although not exclusively, in young men and are usually the result of road traffic accidents or falls. These types of injury may present to either ENT, Maxillofacial, Plastic or Neurosurgery teams, and understanding of a clear management protocol is desirable for each of the specialties. The optimal management of these injuries is becoming more uniformly adopted although some areas of contention still persist. The aim of treatment has always been directed at creating a 'safe sinus' that is not complicated by the late sequelae of infection or mucocele formation. The difficulty lies in being able to predict which patients are likely to develop these complications. The aim of this paper is to evaluate the literature and offer a rationale for the management of these injuries

Hydraulic Fracturing And Reservoir Simulation Modeling Of Enhanced Geothermal System Optimization For Economical Energy Production

Enhanced Geothermal Systems (EGS) have the potential for sustainable energy production but require large upfront expenditures and strategic development to be profitable. To reduce costs and increase energy output, this work integrates hydraulic fracturing (HF) modeling with reservoir simulation optimization to improve EGS design and operating efficiency. EGS uses hot, dry rock geothermal resources, mostly crystalline and sedimentary rocks with poor permeability. Shear stimulation is preferred over hydraulic fracturing in EGS reservoirs, but a comprehensive HF strategy is still lacking. This study fills this gap by evaluating hydraulic fracturing and proppant use for optimal EGS development. Hydraulic fracturing in EGS development lacks a cohesive method; thus, its practicality and cost-effectiveness must be investigated. After thorough literature research, simulation-based pattern modeling evaluates heat capacity, recovery factor, mass flow rate, thermal energy recovery, pressure drop, and heat loss. Laboratory procedures include crushing and SEM analysis evaluate proppants under varied closure stresses. Results suggest high-resistance ceramics are best proppants. Furthermore, a 3D numerical simulation model optimizes fracture patterns, with varying fracture permeability improving extraction efficiency by 38% over 30 years. Net Present Value (NPV) and Levelized Cost of Energy (LCOE) show positive NPV when power prices surpass US$150/MWh, suggesting project feasibility. Below US$120/MWh, NPV is negative, threatening project viability. Integrating hydraulic fracturing modeling and reservoir simulation optimization could improve EGS development efficiency and profitability. Optimizing proppant selection and fracture patterns is key to using EGS for sustainable energy generation

Disulfonated tetraphenyl chlorin (TPCS2a)–induced photochemical internalisation of bleomycin in patients with solid malignancies: A first-in-man phase I dose escalation clinical trial

BACKGROUND: Photochemical internalisation, a novel minimally invasive treatment, has shown promising preclinical results in enhancing and site-directing the effect of anticancer drugs by illumination, which initiates localised chemotherapy release. We assessed the safety and tolerability of a newly developed photosensitiser, disulfonated tetraphenyl chlorin (TPCS2a), in mediating photochemical internalisation of bleomycin in patients with advanced and recurrent solid malignancies. METHODS: In this phase 1, dose-escalation, first-in-man trial, we recruited patients (aged ≥18 to <85 years) with local recurrent, advanced, or metastatic cutaneous or subcutaneous malignancies who were clinically assessed as eligible for bleomycin chemotherapy from a single centre in the UK. Patients were given TPCS2a on day 0 by slow intravenous injection, followed by a fixed dose of 15 000 IU/m2 bleomycin by intravenous infusion on day 4. After 3 h, the surface of the target tumour was illuminated with 652 nm laser light (fixed at 60 J/cm2). The TPCS2a starting dose was 0·25 mg/kg and was then escalated in successive dose cohorts of three patients (0·5, 1·0, and 1·5 mg/kg). The primary endpoints were safety and tolerability of TPCS2a; other co-primary endpoints were dose-limiting toxicity and maximum tolerated dose. The primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00993512, and has been completed. FINDINGS: Between Oct 3, 2009, and Jan 14, 2014, we recruited 22 patients into the trial. 12 patients completed the 3-month follow-up period. Adverse events related to photochemical internalisation were either local, resulting from the local inflammatory process, or systemic, mostly as a result of the skin-photosensitising effect of TPCS2a. The most common grade 3 or worse adverse events were unexpected higher transient pain response (grade 3) localised to the treatment site recorded in nine patients, and respiratory failure (grade 4) noted in two patients. One dose-limiting toxicity was reported in the 1·0 mg/kg cohort (skin photosensitivity [grade 2]). Dose-limiting toxicities were reported in two of three patients at a TPCS2a dose of 1·5 mg/kg (skin photosensitivity [grade 3] and wound infection [grade 3]); thus, the maximum tolerated dose of TPCS2a was 1·0 mg/kg. Administration of TPCS2a was found to be safe and tolerable by all patients. No deaths related to photochemical internalisation treatment occurred. INTERPRETATION: TPCS2a-mediated photochemical internalisation of bleomycin is safe and tolerable. We identified TPCS2a 0·25 mg/kg as the recommended treatment dose for future trials. FUNDING: PCI Biotech

Non-metastatic cutaneous squamous cell carcinoma treated with photodynamic therapy using intravenous mTHPC

INTRODUCTION Photodynamic therapy (PDT) is a method of treating various pathologies. In this retrospective study with prospective intent, a total of 22 patients with T1/T2 N0 cutaneous squamous cell carcinoma (SCC) were treated with intravenous mTHPC (meta-tetrahydroxyphenylchlorin) and surface illumination PDT. Comparisons with the clinical features, rate of recurrence and overall outcome were made. MATERIALS AND METHODS Surface illumination PDT was offered under local anaesthesia. 0.05 mg/kg mTHPC was administered intravenously into the midcubital vein 48 h prior to tissue illumination. 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 Tumors (RECIST). RESULTS Clinical assessment revealed that 16 patients had lesions of <2 cm in size (T1), while the rest were T2. No nodal involvement was identified in any of the patients. None of the patients had a locally recurrent lesion. During the 3-year follow-up, 20/22 patients had complete response (CR) and this was after one round of treatment. Two patients suffered from recurrent disease within 3 years of the follow-up, and they underwent surgical resection. CONCLUSION PDT achieved high efficacy in the treatment of T1N0 cutaneous squamous cell carcinoma with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients

The future of medical diagnostics: Review paper

While histopathology of excised tissue remains the gold standard for diagnosis, several new, non-invasive diagnostic techniques are being developed. They rely on physical and biochemical changes that precede and mirror malignant change within tissue. The basic principle involves simple optical techniques of tissue interrogation. Their accuracy, expressed as sensitivity and specificity, are reported in a number of studies suggests that they have a potential for cost effective, real-time, in situ diagnosis. We review the Third Scientific Meeting of the Head and Neck Optical Diagnostics Society held in Congress Innsbruck, Innsbruck, Austria on the 11th May 2011. For the first time the HNODS Annual Scientific Meeting was held in association with the International Photodynamic Association (IPA) and the European Platform for Photodynamic Medicine (EPPM). The aim was to enhance the interdisciplinary aspects of optical diagnostics and other photodynamic applications. The meeting included 2 sections: oral communication sessions running in parallel to the IPA programme and poster presentation sessions combined with the IPA and EPPM posters sessions. © 2011 Jerjes et al; licensee BioMed Central Ltd

Apparent Complete Response of a Treatment Refractory and Recurrent Squamous Cell Carcinoma Lesion to Photochemical Internalization: A Clinical Case Study

Photochemical internalisation (PCI) depends on the delivery of sub‐lethal 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 0.25mg/kg of TPCS2a (Amphinex®). Surface illumination photochemical internalisation 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 tumour shrinkage was most noticeable at day 14 post‐illumination. 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 post‐illumination and found to be tumour 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

Epithelial tissue thickness improves optical coherence tomography's ability in detecting oral cancer

BACKGROUND OCT is a non-invasive imaging technique that enables the measurement of epithelial thickness and architectural changes, which can help in the diagnosis of pre-cancerous and cancerous lesions. The purpose of the study was to assess whether epithelial tissue thickness improves optical coherence tomography’s ability in detecting oral cancer. PATIENTS AND METHODS Surgically resected oral margins from 60 patients diagnosed with oral squamous cell carcinoma were subjected to OCT. Three OCT measurements (immediate, 1 h and 24 h post-resection) were conducted per resected tissue specimen to look at the effect of saline and formalin on the specimen and its effect on the reproducibility of the OCT. OCT was, then, used to measure the epithelial tissue thickness in cancer-free and cancer-involved margins in eight oral anatomical locations. This data was, then, combined with architectural changes data to calculate the sensitivity and specificity. RESULTS An overall of 189 cancer-free margins and 51 cancer-involved margins had their epithelial thickness measured using OCT and compared to histopathology. With regards to the validity of the OCT and histopathological measurements, epithelial thickness showed good correlation between different readings at all oral sites. With regards to the reproducibility of the OCT measurements, the mean epithelial thickness for all measurements at first (immediate) and second (1 h post-resection – saline preserved) measurements was not significantly different. Underestimation of the epithelial depth in cancer-free margins was 20 μm, while in the cancer-involved margins was 10 μm. Combining data from architectural changes and epithelial thickness, a sensitivity of 92% and a specificity of 94% was achieved. CONCLUSION Oral epithelium measurements using OCT were valid compared to those made with gold standard pathology. Measurements made using OCT was also reproducible with minor underestimation. Epithelial thickness, combined with architectural changes, led to high accuracy in differentiating between cancer-free and cancer-involved margins