Photodynamic therapy and photodiagnosis for Barrett''s oesophagus and early oesophageal carcinoma

Over the last few decades the there has been a huge increase in the incidence of oesophageal adenocarcinoma, surpassing that of any other solid tumour. Barrett's oesophagus is recognised as a pre-malignant cursor. Surveillance programmes have evolved to monitor Barrett's oesophagus, with the intention to detect early malignant transformation. Using photosensitive agents photodiagnosis is developing to detect this transformation before it is visible endoscopically to allow early treatment. Photodynamic therapy is a non-thermal endoscopic ablative technique, which incorporates the same photosensitive agents to treat Barrett's oesophagus as well as malignant disease. In this article we review the present status of photodiagnosis and photodynamic therapy in the management of Barrett's oesophagus and early oesophageal carcinoma.     

Photodynamic therapy for Barrett's oesophagus and oesophageal carcinoma—How I do it

We have considerable experience in the use of both ALA and Photofrin-induced photodynamic therapy in the treatment of Barrett's oesophagus (with and without dysplasia) and both early and advanced oesophageal carcinoma. The drugs used and the techniques vary depending on the condition being treated. The techniques and doses used for the various conditions are outlined here.     

Barrett's oesophagus and photodynamic therapy (PDT)

Barrett's oesophagus is a precursor of oesophageal adenocarcinoma. This cancer has the fastest growing incidence of any solid tumour in the Western world. Surveillance of Barrett's oesophagus is routinely undertaken to detect early malignant transformation. However, ablative endoscopic treatments are available and these can obliterate the abnormal epithelium, allowing neo-squamous re-growth. Photodynamic therapy (PDT) using haematoporphyrin derivative (HpD)/porfimer sodium (Photofrin^®), m-tetrahydroxyphenyl chlorin (mTHPC) and 5-aminolaevulinic acid (ALA) utilise such a technique. In this non-thermal method of ablation, the photosensitisers, together with light and oxygen, produce local tissue destruction. The use of PDT ablation of Barrett's oesophagus is reviewed.     

Photodynamic therapy for Barrett''s oesophagus: How I do it

Endoscopic photodynamic therapy (PDT) for Barrett's oesophagus with high-grade dysplasia or early carcinoma is undertaken after full investigation. Endoscopic assessment is mandatory to determine the extent of the Barrett's segment and neoplastic changes. Photofrin at 2 mg/kg bw is used, followed 24–72 h later by illumination of 630 nm light, 200 J/cm of lesion. The whole of the Barrett's segment should be exposed to illumination. Patients are followed up endoscopically at 3 months.     

Photodynamic therapy for Barretts’ adenocarcinoma associated with an Angelchik device

We present a novel case of an elderly patient with a Barrett's adenocarcinoma in the presence of an Angelchik prosthesis. We aim to draw attention to issues relating to metaplastic Barretts’ oesphagus and its adenocarcinoma complications and highlight relevant issues in multimodal endoscopic management and palliation using photodynamic therapy in the presence of the device.     

Endoscopic photodynamic therapy for oesophageal disease

Photodynamic therapy is a very important technique for the eradication of widespread oesophageal mucosal disease which has the potential to degenerate to cancer. Patients unsuitable or unwilling to undergo radical therapy can be cured using photodynamic therapy. We predominantly treat patients with high-grade dysplasia in Barrett's oesophagus. Lesions that are visible macroscopically are removed using endoscopic mucosal resection. The remaining area is then treated in 5 cm segments at 3 monthly intervals with separate photosensitisation using endoscopic photodynamic therapy.     

The current role of photodynamic therapy in oesophageal dysplasia and cancer

Over the last 15 years photodynamic therapy (PDT) has become a viable treatment for pre-malignant and malignant disease of the oesophagus. Its initial use was in the palliation of oesophageal malignant obstruction bringing improved swallowing hence increasing nutritional intake and improving general quality of life. As the therapeutic boundaries of PDT have stretched, current studies look at the role of PDT in the treatment of pre-malignant dysplastic Barrett's epithelium and early malignancy as a curative mucosal ablative technique. As a curative treatment in early oesophageal cancer, PDT provides an alternative treatment to oesophagectomy for those more elderly or less medically fit patients.This paper reviews the uses of photodynamic therapy in oesophageal cancer with reference to the available publications on its use in the palliation of oesophageal cancer and treatment of early cancer and high grade dysplasia in Barrett's mucosa.     

Barrett食管的光动力学治疗

探讨光动力学疗法（PDT）治疗Barrett食管的有效性。对比各种类型光敏剂治疗Barrett食管的优点和不足，比较PDT与其他内镜下治疗Barrett食管的疗效及其并发症。PDT疗法Barrett食管具有损伤小，造成穿孔等并发症的机会较小，且对于一些边界不清或者多病灶的病变可减少治疗遗漏等特点，但可造成食管狭窄且某些光敏剂需要长达一个月的避光期造成患者治疗期间不方便。PDT是一种可重复性，侵袭性小，特异性强而疗效可靠的一种治疗Barratt食管的方法，不仅对不典型增生而且对早期癌都有疗效，与其他内镜下治疗联合可提高治疗效果。     

PDT for Barrett's esophagus: Status and unsolved problems

PDT had been proposed in gastroenterology for various indications and the esophageal cancer treatment had been among the very first having been approved. However, PDT failed to be a real breakthrough. One reason for it was that although it had been approved for the palliative treatment of advanced tumors, PDT only has by nature a limited in-depth efficacy fitting better to the treatment and often the cure of “early cancers”. For this reason PDT has also been proposed for the treatment of Barrett's esophagus (BE) with high-grade dysplasias. Barrett's mucosa (BM) is a field of a specialized metaplastic columnar epithelium replacing the normal stratified squamous epithelium or mucosa lining the distal esophagus. In this case, PDT has to destroy an area of thin tissues spread eventually over a wide area instead of a mass of tissues. Something important is that existing treatments allow the treatment of foci of dysplastic tissues but not the regression of the whole BM. BE is thus an unsolved medical problem having medical as well as economic consequences as BM being likely to transform into a cancer has to be carefully surveyed. The esophageal cancer, an adenocarcinoma, has to be surgically removed when it is possible something pretty heavy with a high morbidity. Economic burnt is also important with high survey costs independently to the additional surgical costs in case of diagnosed cancer.Treatments proposed for non or mild dysplastic BM regression have in common to have an inhomogenous impact on the target. Treatments for high-grade dysplasia (HGD, the ultimate pathological step before cancer) are based on mucosectomy and are limited to small areas of tissues. Recently circumferential mucosectomy had been proposed but at a higher risk making it suitable only to highly experienced hands in infrequent indications.     

Photodynamic therapy for prostate cancer: One urologist's perspective

Photodynamic therapy (PDT) has slowly found its place in the treatment of human disease. Currently, photodynamic therapy is being explored as a treatment option for localized prostate cancer. PDT for the treatment of prostate cancer will require ablation of both malignant and non-malignant glandular epithelium. Ablation of both malignant and normal epithelium adds a new treatment dimension since traditionally PDT has not targeted normal epithelial tissue. PDT for prostate cancer as currently envisioned will present challenges in terms of in situ monitoring of light, drug concentration, p_O2 levels and biologic endpoints. The introduction of vascular-targeted photosensitizers fundamentally alters the traditional axioms for successful PDT treatment by obviating the need for “selective” tumor localization. Should clinical trials demonstrate the utility of this approach, patients with organ-confined disease will benefit.     

Photodynamic therapy in dermatology beyond non-melanoma cancer: An update

Photodynamic therapy (PDT) employs a photosensitizer (PS) and visible light in the presence of oxygen, leading to production of cytotoxic reactive oxygen species, which can damage the cellular organelles and cause cell death. In dermatology, PDT has usually taken the form of topical application of a precursor in the heme biosynthesis pathway, called 5-aminolevulinic acid (or its methyl ester), so that an active PS, protoporphyrin IX accumulates in the skin. As PDT enhances dermal remodeling and resolves chronic inflamation, it has been used to treat cutaneous disorders include actinic keratoses, acne, viral warts, skin rejuvenation, psoriasis, localized scleroderma, some non-melanoma skin cancers and port-wine stains. Efforts are still needed to mitigate the side effects (principally pain) and improve the overall procedure.     

Photodynamic therapy for tracheal thyroid metastasis

We report the case of a patient with recurrence of follicular carcinoma of the thyroid 8 years after surgical resection followed by external beam radiotherapy and radio-iodine treatment. The patient was treated by endoscopic photodynamic therapy (PDT) with complete endoscopic response after 12 months with good symptom relief.     

Photodynamic therapy in the palliative treatment of esophageal cancer

Esophageal carcinoma is one of the most common cancers in the world and has an increasing incidence in Western civilisation and poor prognosis. In most cases palliative treatment is the only kind of therapy, which can be applied.In the Department of Digestive Tract Diseases, Medical University, Lodz, Poland, we have used PDT in two cases of palliative therapy of advanced esophageal cancer in cervical location of esophagus.We find PDT very promising, minimally invasive, safe and easy technique to perform for esophageal cancer of cervical localization.     

Photodynamic therapy for chest wall recurrence from breast cancer

Breast cancer is common with over 230,000 new cases diagnosed each year in North America alone. While great strides have been made to achieve excellent cancer control and survival, a significant minority of patients fail locally. While initial salvage to regain disease control is of the utmost importance, it is not universally successful. This leads to a therapeutic quagmire. Additional surgery, radiation and chemo-hormonal therapy are possible, but they are usually highly morbid with low success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate patient population. This report analyzes and reviews the role of photodynamic therapy for patients with chest wall re-recurrence from breast cancer.     

Photodynamic therapy as initial treatment for small choroidal melanomas

PurposeTo evaluate Verteporfin photodynamic therapy (PDT) as primary treatment for small, posterior choroidal melanoma.DesignRetrospective cohort review.Subjects, participants and controlsRetrospective case note review of 20 patients with small juxtapapillary and juxtafoveal choroidal melanomas treated with PDT at the Liverpool Ocular Oncology Clinic.MethodsPatient and tumour characteristics, PDT session details, visual acuity and B-scan ultrasonography measurements as well as colour fundus photographs at each examination were collated and analysed.Main outcome measuresLocal tumour control and Best Corrected Visual Acuity (BCVA).ResultsThe 20 patients (14 male, 6 female) had a mean age of 61.2 years (range, 40–85) and were treated between 2001 and 2012. Seven tumours were amelanotic, while 13 were pigmented. Of 20 melanomas, 11 (55%) showed complete regression on B-scan ultrasonography and colour photography; five (25%) showed partial regression; four (20%) remained unchanged and two (10%) showed further growth, for which alternative standard treatment was required. Baseline BCVA was 0.1 logMAR (mean; range 0.0–0.6) compared to a post-PDT BCVA of 0.4 logMAR (mean; range −0.2 to 1.7) over a follow-up of 60.0 months (mean; range 25–156 months).ConclusionsPDT can induce tumour regression in a significant proportion of small, posterior, choroidal melanomas but is less reliable than other forms of therapy. It may have a role in patients with special visual requirements if they accept the increased risk of treatment failure requiring radiotherapy.     

Photodynamic therapy for pancreatic carcinoma: experimental and clinical studies

Pancreatic carcinoma is the sixth leading cause of cancer-related mortality in the United Kingdom, with an overall 5-year survival of less than 5%. Attempted curative surgery is possible in less than 20% of cases and is associated with a 5-year survival of just 10–20%. Palliative radio-chemotherapy improves symptoms of pancreatic cancer but rarely extends median survival beyond 12 months. There is a need to develop novel therapies that improve outcome. Photodynamic therapy, which is a way of producing localised non-thermal tissue necrosis with light, is currently under evaluation as a treatment for pancreatic cancer. This review will examine some of the mechanisms underlying photodynamic therapy, and the preclinical work, which has led to this treatment being piloted in human studies.     

Photodynamic therapy for onychomycosis: A systematic review

Other than a cosmetic concern, Onychomycosis is also a prevalent nail disease, which is extremely difficult to treat, and sometimes is refractory to conventional therapy. Moreover, many patients are not eligible to take oral antifungals owing to polypharmacy and comorbidities. Systemic side effects seen with oral antifungals have lead to patient nonadherence and adverse events. Therefore, newer therapies are being investigated for onychomycosis that would be free of systemic complications posed by oral therapy. Photodynamic therapy (PDT) is one of those being currently studied, which involves the use of photosensitizer and a light source to excite the photosensitizer to generate reactive oxygen species. The present review will put some light on PDT as an upcoming treatment modality for onychomycosis. We performed a systematic review of the literature to find the articles relevant to the use of PDT for onychomycosis. From the primary search of 43 articles, 17 papers are included in this review.