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

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

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.     

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up

ObjectivesPhotodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up.Materials and methodsThirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm² using a 630-nm wavelength excimer dye laser.ResultsSix months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed.ConclusionPDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.     

Widespread osteolytic lesions of the long bones in basal cell nevus syndrome

Three members of a family, father, daughter, and son, with the basal cell nevus syndrome are presented. A very unusual manifestation of widespread cyst-like osteolytic lesions in all the tubular bones was observed in the father, together with osteoblastic spotty osteopoikilotic lesions in the skull and the mandible of the same patient. Cyst-like osteolytic lesions have been described previously in this syndrome, mainly in the phalanges. We believe that such lesions can occur in any bone.     

How we treat a superficial basal cell carcinoma with topical photodynamic therapy in Dundee

Topical photodynamic therapy (PDT) is a highly effective treatment for superficial basal cell carcinoma (SBCC) (Morton CA, Brown SB, Collins S, et al. Guidelines for topical photodynamic therapy: report of a workshop of the British Photodermatology Group. Br J Dermatol 2004;146:552–67). Treatment is well tolerated, performed on an outpatient basis and can be repeated, and excellent outcomes and cosmetic results can be achieved. We have experience of over 3000 topical PDT treatments for superficial non-melanoma skin cancer and dysplasia in the Photobiology Unit in Dundee and I will present our own experience of how to treat an SBCC with topical PDT in this article (Ibbotson SH, Moseley H, Brancaleon L, et al. Photodynamic therapy in dermatology: Dundee clinical and research experience. Photodiagn Photodyn Ther 2004;1:211–23).     

Photodynamic therapy in the management of pre-malignant head and neck mucosal dysplasia and microinvasive carcinoma

The management of head and neck mucosal dysplasia and microinvasive carcinoma is an appealing strategy to prevent the development of invasive carcinomas. While surgery remains the standard of care, photodynamic therapy (PDT) offers several advantages including the ability to provide superficial yet wide field mucosal ablative treatment. This is particularly attractive where defining the extent of the dysplasia can be difficult. PDT can also retreat the mucosa without any cumulative fibrotic complications affecting function. To date, clinical experience suggests that this treatment approach can be effective in obtaining a complete response for the treated lesion but long term follow-up is limited. Further research efforts are needed to define not only the risk of malignant transformation with PDT but also to develop site specific treatment recommendations that include the fluence, fluence rate and light delivery technique.     

Photodynamic therapy (PDT) of lung cancer: experience of the Tokyo Medical University

Endoscopic low (Photodynamic therapy (PDT)) or high (vaporization) power laser treatment has been recognized as a lung-sparing local therapeutic modality that can achieve remarkable responses. This paper reviews the experience of our institution since 1978 in the treatment of lung cancer using laser. Endoscopic ablation of tracheobronchial malignancies is mainly intended to reduce respiratory distress and improve quality of life. Effective results were obtained in 143 (81%) of the 177 lesions. PDT is extremely attractive and has been used for the various purposes. In the curative PDT for centrally located early stage lung cancer, complete response (CR) rate was achieved in 86.4% (165 out of 191 lesions). Overall 5-year survival rate was 57.6% and the lung cancer specific 5-year survival rate was 92.5%. With regard to palliative PDT to opening obstructed bronchi in advanced cases, more than 50% opening of the obstruction was accomplished in 75%. Preoperative PDT was performed in 32 patients with lung cancer for the purpose of either reducing the extent of resection or increasing operability. The initial purpose of PDT was achieved in 27 of 32 patients treated. Conversion to an operable condition was achieved in 4 of 5 originally inoperable cases. In 23 of 27 patients who were originally candidates for pneumonectomy, it became possible to reduce the extent of resection to lobectomy or sleeve lobectomy. PDT could be used to treat peripheral tiny lung cancers safely and without unacceptable effects on surrounding tissue. The authors believe that PDT has a great potential and will achieve further development in the future.     

氨基酮戊酸光动力疗法治疗基底细胞癌

目的观察氨基酮戊酸-光动力疗法（5-aminolevulinic acid photodynamic therapy,5-ALA-PDT）治疗基底细胞癌的疗效。方法基底细胞癌患者42例,局部采用5-ALA-PDT治疗。20%ALA霜剂涂于患者皮损和周围正常皮肤0.5～1.0 cm处,厚度约1 mm,持续湿敷,外加塑料薄膜封包,4 h后He-Ne激光照射,功率密度100～200 mW/cm^2,时间30 min,每次能量密度180～360 J/cm^2,两次光动力治疗时间间隔1～2周,共治疗3～6次。结果 42例基底细胞癌中,完全缓解29例,部分缓解8例,总有效率88.1%;39例（92.9%）患者美容效果满意;无一例患者出现严重不良反应。结论局部5-ALA-PDT治疗基底细胞癌安全有效、美容效果好、不良反应少。     

Photodynamic therapy activated STAT3 associated pathways: Targeting intrinsic apoptotic pathways to increase PDT efficacy in human squamous carcinoma cells

5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC–Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation (p< 0.05), but there was no significant difference when the photosensitizer reached to 4.8 mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle (p < 0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24 h after 5-ALA-PDT treatment.     

Visualization of basal cell carcinoma by fluorescence diagnosis and independent component analysis

Photodynamic detection (PDD) of skin tumours is based on the visualization of a fluorophores, with the ability to accumulate in tumour tissue, by the use of fluorescence imaging. Of particular importance is the application of δ-5-aminolaevulinic acid (ALA) that, through the process of biosynthesis causes formation of the protoporphyrin IX (PpIX). The PpIX has the ability of selective fluorescence after basal cell carcinoma (BCC) has been treated with ALA. Higher concentration of PpIX in tumour tissue compared to surrounding normal skin is the basis for PDD. Our contribution in this preliminary study is application of the independent component analysis (ICA) to extract the BCC spatial map, by processing fluorescent RGB image acquired under excitation with 405 nm light. Comparative performance analysis with other two widely used image processing methods: ratio imaging and optimal threshold based imaging, reveals that ICA produces BCC spatial map that is most consistent in term of diagnostic quality by both visual assessment and calculation of the BCC demarcation line. We believe this represents a solid basis for the design of a compact and low-cost multi-spectral fluorescence imaging system, capable for real time calculation of the skin tumour demarcation.     

Intracranial extension of basal cell carcinoma of the scalp

A case of recurrent basal cell carcinoma of the right occipital scalp is reported. Plain film, CT, and MRI examinations of the head demonstrated direct neoplastic invasion through the occipital bone and meninges into the right cerebellar hemisphere.     

Photodynamic therapy and endoscopic mucosal resection as minimally invasive approaches for the treatment of early esophageal tumors: Pre-clinical and clinical experience in Lausanne

Esophageal cancer, when detected at an early stage, has a very good probability of being eradicated by surgery or radiotherapy. However, less aggressive treatments also tend to provide high rates of cure without the side effects of radical surgery or radiotherapy. Among them, photodynamic therapy and endoscopic mucosal resection have been experienced as alternative techniques for mucosal ablation in patients with superficial squamous-cell carcinoma (SCC) of the esophagus, or high-grade dysplasia and early stage adenocarcinoma arising in Barrett's esophagus. We report on the results of our clinical experience with photodynamic therapy and discuss about its advantages and limitations. We also present a pre-clinical study, which had evaluated the feasibility, efficacy, and safety of a promising new method of endoscopic mucosal resection (EMR) based on the use of a modified rigid esophagoscope. The animal model chosen was the sheep because of its similarities with humans regarding the thickness and histologic structure of the esophagus. This new resection modality offers a promising approach in comparison with other options currently available, namely EMRs performed with flexible gastroscopes. It appears to be superior in terms of the size of the resected specimen, the precision and regularity of the resection depth, and the accuracy of histological diagnosis with safety margins.     

基底细胞痣综合征的影像诊断简

目的探讨基底细胞痣综合征（BCNS）特征性的临床、影像及病理表现。方法对我院收治的2例经病理证实患者的临床及影像资料进行报道及回顾性分析,并进行相关文献复习。结果2例均有特征性的颌骨多发囊肿,肋骨分叉;其中1例有颅内异常钙化。结论目前文献对BCNS确诊的病例报道较少。由于BCNS具有临床及影像特征表现,因此提高对该病的认识,对临床早期诊断及治疗有积极的意义。