Prognosis of oral epithelial dysplasia in individuals with and without oral lichen planus.

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.

Structural validation of facial skin using optical coherence tomography: A descriptive study.

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.

Periorbital skin cancers subjected to mTHPC-photodynamic therapy: A prospective study.

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.

Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man 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/m(2) 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/cm(2)). 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.

mTHPC-mediated photodynamic therapy of early stage oral squamous cell carcinoma: a comparison to surgical treatment.

BACKGROUND: mTHPC-mediated photodynamic therapy (PDT) is used for treatment of early head and neck squamous cell carcinoma. This study is a retrospective comparison of PDT with transoral surgery in the treatment of early primary squamous cell carcinoma of the oral cavity/oropharynx. METHODS: PDT data were retrieved from four study databases; surgical results were retrieved from our institutional database. To select similar primary tumors, infiltration depth was restricted to 5 mm for the surgery group. A total of 126 T1 and 30 T2 tumors were included in the PDT group, and 58 T1 and 33 T2 tumors were included in the surgically treated group. RESULTS: Complete response rates with PDT and surgery were 86 and 76% for T1, respectively, and for T2 63 and 78%. Lower local disease-free survival for PDT compared to surgery was found. However, when comparing the need for local retreatment, no significant difference for T1 tumors was found, while for T2 tumors surgery resulted in significantly less need for local retreatment. No significant differences in overall survival between surgery and PDT were observed. CONCLUSIONS: PDT for T1 tumors results in a similar need for retreatment compared to surgery, while for T2 tumors PDT performs worse. Local disease-free survival for surgery is better than for PDT. This may be influenced by the benefit surgery has of having histology available. This allows an early decision on reintervention, while for PDT one has to follow a wait-and-see policy. Future prospective studies should compare efficacy as well as morbidity.

Strategies of airway management for head and neck photo-dynamic therapy.

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive treatment modality which has great clinical implications, especially in head and neck oncology. Post-operative swelling is a well-documented consequence of PDT. It is paramount the airway remains patent for these patients. A tracheostomy remains the gold standard treatment modality for base of tongue tumours susceptible to post operative PDT inflammation, which can lead to a compromised airway. We have carried out a retrospective study to outline the airway management strategies employed for head and neck cancer patients treated with PDT and suggest recommendations for future management. MATERIALS AND METHODS: This retrospective clinical study utilises 88 patients (53 males and 35 females) treated at the UCLH Head and Neck Center, London (between 2006 and 2013), for treatment of various lesions with superficial and/or interstitial PDT, when the airway could potentially be compromised. RESULTS: Of the 88 patients selected 60 had interstitial PDT (iPDT) and 13 had superficial PDT (sPDT). Fifteen patients were treated with both iPDT and sPDT. Among the iPDT patients 19 had a trachestomy; two patients a Quicktrach; four a Cook Airway Exchange Catheter (CEAC); one a percutaneous tracheostomy; one a needle tracheostomy and 33 patients did not receive any temporary airway pathways. Among the sPDT patients two had a trachestomy. Although the majority of patients did not suffer any major incidents, one sPDT patient required an emergency tracheostomy two days post-operatively. CONCLUSION: Airway management is vital when planning PDT treatment for tongue based tumours. Consider a more conventional approach when the lesion being targeted is located at a higher risk site: Floor of mouth/posterior tongue/tongue base or when multiple oral sites are being treated.

Emerging potential of phototherapy in management of symptomatic oral lichen planus: A systematic review of randomised controlled clinical trials.

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.

Early experience of thalidomide therapy for high-grade peripheral and facial arteriovenous malformations.

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.

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance.

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.

Stromal features are predictive of disease mortality in oral cancer patients.

Worldwide, approximately 405 000 cases of oral cancer (OSCC) are diagnosed each year, with a rising incidence in many countries. Despite advances in surgery and radiotherapy, which remain the standard treatment options, the mortality rate has remained largely unchanged for decades, with a 5-year survival rate of around 50%. OSCC is a heterogeneous disease, staged currently using the TNM classification, supplemented with pathological information from the primary tumour and loco-regional lymph nodes. Although patients with advanced disease show reduced survival, there is no single pathological or molecular feature that identifies aggressive, early-stage tumours. We retrospectively analysed 282 OSCC patients for disease mortality, related to clinical, pathological, and molecular features based on our previous functional studies [EGFR, αvß6 integrin, smooth muscle actin (SMA), p53, p16, EP4]. We found that the strongest independent risk factor of early OSCC death was a feature of stroma rather than tumour cells. After adjusting for all factors, high stromal SMA expression, indicating myofibroblast transdifferentiation, produced the highest hazard ratio (3.06, 95% CI 1.65-5.66) and likelihood ratio (3.6; detection rate: false positive rate) of any feature examined, and was strongly associated with mortality, regardless of disease stage. Functional assays showed that OSCC cells can modulate myofibroblast transdifferentiation through αvß6-dependent TGF-ß1 activation and that myofibroblasts promote OSCC invasion. Finally, we developed a prognostic model using Cox regression with backward elimination; only SMA expression, metastasis, cohesion, and age were significant. This model was independently validated on a patient subset (detection rate 70%; false positive rate 20%; ROC analysis 77%, p < 0.001). Our study highlights the limited prognostic value of TNM staging and suggests that an SMA-positive, myofibroblastic stroma is the strongest predictor of OSCC mortality. Whether used independently or as part of a prognostic model, SMA identifies a significant group of patients with aggressive tumours, regardless of disease stage.

Long-term outcomes following Foscan®-PDT of basal cell carcinomas.

BACKGROUND AND OBJECTIVE: In a previous publication we showed that mTHPC-PDT (Foscan®-PDT) is an effective treatment of basal cell carcinomas (BCCs) in "difficult to treat" locations and presented optimized treatment parameters to reduce costs and side effects. Now we present long-term results of the same study population. STUDY DESIGN/MATERIALS AND METHODS: Following PDT of a total of 460 BCCs in 117 subjects, the patients/lesions were followed-up for a mean duration of 42 (range: 2-72) months. Two patients dropped out of follow-up; 13 patients died of unrelated causes. Recurrences were treated either by repeated PDT or other established methods. RESULTS: The sustained clearance rate was 93.7% and the overall treatment success rate was 90.7%. Kaplan-Meier analysis revealed an estimated recurrence free fraction of patients at 5 years of 95.1%, 92.4%, 85.1%, and 74.0% for the four different photosensitizer dose groups (0.06-0.15, 0.05, 0.04, and 0.03 mg/kg). High-risk lesions (recurrences, thickness >3 mm) recurred more often than low-risk ones, and recurrences mostly (>50%) occurred during the first year of follow-up. CONCLUSION: Long-term outcomes of high-dose (0.06-0.15 mg/kg) and reduced-dose (0.05 mg/kg) Foscan®-PDT in "difficult to treat" BCCs compare favorably with other methods, even in high-risk lesions (recurrent and/or thick lesions). A recommended combination of treatment parameters for low-dose therapy seems to be: 0.05 mg/kg Foscan®, 24 hours drug-light interval (DLI), fluence ≥40 J/cm(2) . Prospective randomized studies are needed to look into low-dose mTHPC-PDT of BCCs in more detail and to directly compare it with other treatments.

CO2 laser of oral dysplasia: clinicopathological features of recurrence and malignant transformation.

The use of the CO(2) laser in the management of oral dysplastic lesions has become a more common practice. Very few studies have evaluated recurrence, residual disease malignant transformation, and overall outcome in patients undergoing such a procedure. In this prospective study, a total of 123 oral dysplastic lesions from 77 consecutive patients were treated with the CO(2) laser (resection and/or ablation). The average age was 58 ± 4.8 years. The patients' recovery was uneventful and no complications were reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 6.4 years, and biopsies taken in case of changes suggestive of malignant development. Homogenous leukoplakias were identified in 31 patients, non-homogenous leukoplakias in 34 patients, whereas 12 patients had erythroplakias. Ex- and life-long smokers formed 88.3% of the recruited patients. While people who currently smoke and drink formed 55.8% of the cohort. Erythroplakias were solely identified in heavy life-long smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth, and buccal mucosa. Moderate dysplasia was identified in 42 patients while 18 patients had severe dysplasia. Laser resection margins in selected cases (68 patients) were clear in 53 and showed mild-moderate dysplasia in the involved margins. The rate of recurrence had no significant association with the location but the severity of epithelial dysplasia. The rate of first recurrence after laser surgery was approximately 19.5%. Malignant transformation was observed in eight patients (10.4%), in the tongue and the floor of mouth. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. Laser resection/ablation is recommended for oral dysplasia to prevent not only recurrence and malignant transformation but also postoperative oral dysfunction encountered by other conventional modalities.

Quality of life following photodynamic therapy for head and neck pathologies: An exploratory study.

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.

In vivo evaluation of traumatic and malignant oral ulcers with optical coherence tomography: A comparison between histopathological and ultrastructural findings.

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.

Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India.

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.

Interstitial PDT for vascular anomalies.

INTRODUCTION: Photodynamic therapy is a proven therapeutic modality in the management of variety of pathologies involving the human body. Our aim in this clinical study is to prospectively evaluate the outcome following interstitial photodynamic therapy for patients with vascular anomalies. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. MATERIALS AND METHODS: Forty-three patients were referred to the UCLH Head and Neck Centre for treatment of vascular anomalies of the head and neck, including: infantile and congenital haemangiomas, venous, lymphatic and arteriovenous malformations. After multidisciplinary discussion, all patients underwent interstitial photodynamic therapy under general anaesthesia, using 0.15 mg/kg mTHPC as the photosensitising agent. Following treatment, patients were followed-up for a mean of 21 months. RESULTS: Fifteen out of nineteen patients who presented with long-term pain reported improvement after treatment. Also, 7/8 reported significant reduction of bleeding related to their vascular anomaly. Improvement of swelling was reported by 28/35 patients; while reduction of infection episodes was evident in 8/11 patients and 31/36 reported reduction in the disfigurement caused by their pathology. Significant reduction of swallowing problems was reported in 9/12 patients, and breathing problems in 7/9 patients. Clinical assessment showed that half of the patients had 'good response' to the treatment. Moderate clinical response was reported by 13 (30.2%) patients. Radiological assessment comparing imaging 6-week post-PDT to the baseline showed moderate response in 11 (25.6%) patients and significant response in 15 (34.9%) patients. CONCLUSION: This study on 43 patients with vascular anomalies undergoing interstitial photodynamic therapy provided evidence that PDT is a successful modality in the management of these pathologies that are resistant to conventional modalities, with minimal side effects.

Photodynamic therapy outcome for oral dysplasia.

INTRODUCTION: Photodynamic therapy (PDT) is a minimally invasive surgical intervention used in the management of tissue disorders. It can be applied before, or after, any of the conventional modalities, without compromising these treatments or being compromised itself. MATERIALS AND METHODS: In this prospective study, a total of 147 consecutive patients with oral potentially malignant disorders were treated with surface illumination PDT, using 5-ALA or mTHPC as the photosensitizer. The average age was 53 ± 8.9 years. The patients' recovery was uneventful and no complications reported. Comparisons with the clinical and histopathological features and rate of recurrence as well as malignant transformation were made. The patients were followed-up for a mean of 7.3 years. ANALYSIS AND RESULTS: Homogenous leukoplakias were identified in 55 patients, non-homogenous leukoplakias in 73 patients, whereas 19 patients had erythroplakias. Ex- and current lifelong smokers formed 84.4% of the recruited patients. While people who currently smoke and drink formed 38.1% (56 patients) of the cohort. Erythroplakias were mainly identified in heavy lifelong smokers. The most common identified primary anatomical locations were the lateral border of tongue, floor of mouth and retromolar area. Moderate dysplasia was identified in 33 patients while 63 patients had severe dysplasias; and 32 patients had a histopathological diagnosis of carcinoma in situ. The rate of recurrence in laser surgery was approximately 11.6%. Malignant transformation was observed in 11 patients (7.5%), in the tongue, floor of mouth and retromolar area. Recurrence and malignant transformation was mainly identified in erythroplakias and non-homogenous leukoplakias. The final outcome of the cohort showed that 11 (7.5%) suffered from progressive disease, 5 (3.4%) had stable disease, 12 (8.2%) were considered partially responsive to the therapy. Complete response was identified in 119/147 patients (81%). CONCLUSION: 5-ALA-PDT and/or mTHPC-PDT offer an effective alternative treatment for oral potentially malignant disorders.

Photodynamic therapy outcome for T1/T2 N0 oral squamous cell carcinoma.

INTRODUCTION: This new prospective clinical study assessed the oncological outcomes following surface illumination mTHPC-photodynamic therapy of T1/T2 N0 oral squamous cell carcinoma (OSCC) patients. MATERIAL/METHODS: Thirty-eight patients participated in this study. Their mean age at the first diagnosis of OSCC was 58.0 years. Common clinical presentation was an ulcer mainly identified in the tongue, floor of mouth (FOM), or buccal mucosa. Current and ex-smokers represented 89.5% of the cohort; while current and ex-drinkers were 86.8%. Clinically nine patients had T1 disease while 29 had T2 disease. RESULTS: Pathological analysis revealed that 12 patients had well differentiated SCC, 16 moderately differentiated and 10 had poorly-differentiated cancer. All patients were discussed in a multidisciplinary meeting and, subsequently, underwent mTHPC-PDT. PDT was repeated in 6- to 7-month period following the first round when residual tumor was identified in the treated site. At last clinic review post-PDT, 26/38 patients showed complete normal clinical appearance of their oral mucosa in the primary tumor site. Recent surgical biopsies from the study cohort showed that 17 had normal mucosa, five with hyperkeratinization, 10 with dysplastic changes and six showed recurrent SCC. The overall recurrence was 15.8% and the 5-year survival was 84.2%. Death from loco-regional and distant disease spread was identified in three patients. The recurrence group comprised six patients. Most common presentation was an ulcer involving the buccal mucosa or retromolar area, identified in current or ex-smokers and current drinkers. The surgical margins in this group were also evaluated following laser or surgical excision and reconstruction. CONCLUSIONS: mTHPC-photodynamic therapy (up to three rounds) is a comparable modality to other traditional interventions in the management of low-risk tumors of the oral cavity. Although, sometimes, multiple rounds of the treatment is required, morbidity following PDT is far less when compared to the three conventional modalities: surgery, radiotherapy, and chemotherapy.

Photodynamic therapy: The minimally invasive surgical intervention for advanced and/or recurrent tongue base carcinoma.

INTRODUCTION: The management of tongue base carcinoma continues to be a major challenge in head and neck oncology. Our aim in this prospective study was to evaluate the outcome following ultrasound-guided interstitial photodynamic therapy (US-iPDT) of stage IV tongue base carcinoma patients. Patients' reports on quality of life with clinical and radiological evaluation were the main end point parameters used to assess the outcome. MATERIAL AND METHODS: Twenty-one consecutive patients referred to the UCLH Head and Neck Centre for treatment of advanced and/or recurrent tongue base cancer were included in this study. Two-thirds of the referred patients had not been offered further conventional therapeutic options apart from palliative treatment. It was decided, by the multidisciplinary team, that the only available option was to offer US-iPDT under general anesthesia, using mTHPC (Foscan®) as the photosensitizing agent. Following treatment, patients were followed-up for a mean of 36 months (min. 21, max. 45). RESULTS: Nine of the 11 patients who presented with breathing problems reported improvement after treatment. Also, 19 of the 21 patients reported improvement of swallowing. Improvement of speech was reported by 11 of 13 patients. Clinical assessment showed that more than half of the patients had "good response" to the treatment and about a third reported "moderate response." Radiological assessment comparing imaging 6-week post-PDT to the baseline showed stable pathology with no change in size in four patients, minimal response in seven patients, moderate response in six patients, and significant response in two patients. Eight patients died; four of which due to loco-regional disease; and two from distant tumor spread. Kaplan-Meir survival curve was generated from the survival and follow-up data. CONCLUSIONS: Photodynamic therapy is a successful palliative modality in the treatment of advanced and/or recurrent tongue base carcinoma.

An explanation for the worsened prognosis in some cancer patients of perioperative transfusion: the time-dependent release of biologically active growth factors from stored blood products.

Over 25 years ago Francis reported an association between blood transfusion and worsened cancer prognosis. Subsequently there has been much debate over whether there is in fact such an association, and if so, what is its underlying mechanism. Allogeneic blood transfusion is the most frequent allo-transplantation procedure performed on a routine basis with no prior HLA-typing. 50% of the recipients of unprocessed red cells and platelets become allo-immunised. It is our proposition that as result of normal physiological ageing and metabolic processes (with depletion of ATP and reduction of active membrane processes), there is leaching of biologically active substances from the cells into stored blood products. These leached bioactive substances have immuno-modulatory effects, which may in part explain the increased likelihood of postoperative sepsis and adult respiratory distress syndrome in transfusion recipients. They also promote cell growth and angiogenesis and may therefore have a direct effect on tumour growth. We provide evidence to support a possible hypothesis which could explain much of the conflicting clinical and experimental evidence.