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.     

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。     

光动力学-微循环效应研究方法的建立与评价

目的改进活体微循环观测方法,建立更适合光动力学研究的微循环观察方法并加以验证。 方法采用Wistar大鼠肠系膜微循环观察模型,通过微循环血流流态、红细胞流柱宽度和血流流速三种指标评价该方法是否适合于光动力学-微循环效应的研究,并通过光敏剂介导的光动力学-微循环损伤效应予以验证。实验分为空白对照组、单纯激光组、单纯光敏剂HpD组、HpD-PDT组。每组Wistar大鼠10只。 结果实验观察120min,活体肠系膜微循环观察组血流流态正常,未见明显红细胞聚集、微血栓形成等改变,红细胞流柱宽度百分率未见明显下降（P〉0.05）,血流速度未见明显减慢（P〉0.05）。单纯激光组和单纯光敏剂组对微循环无明显影响,与观察的活体肠系膜微循环空白对照组比较差异无显著意义（单纯激光组P〉0.05;单纯光敏剂组P〉0.05）。在观察光动力学效应的HpD-PDT组,可见明确的光动力学损失效应,与空白对照组之间差异有显著意义（P〈0.05）。 结论改良大鼠肠系膜-活体微循环观察技术,方法可行,能够在较长时间内维持微循环正常的结构和循环动态,实现对微循环光动力学损伤效应的动态观察。     

B超引导经皮介入光动力治疗中晚期肝癌30例

为探讨治疗中晚期肝癌的理想方法，扩大和发展光动力疗法，自１９９４年６月起，我们应用光动力疗法（ＰＤＴ）治疗中晚期肝癌３０例，其中肝细胞癌２８例、腺癌２例。肿瘤直径７～１０ｃｍ的１３例、１０ｃｍ以上至１６ｃｍ的１７例。伴肺转移５例、骨转移５例、门静脉或腔静脉浸润４例。首次治疗１９例、其他方法治疗无效或复发者１１例。本研究采用氩激光泵浦染料激光器系统，获得６３０ｎｍ波长的连续波治疗光。光敏剂选用血卟啉衍生物（ＨｐＤ）。治疗时通过Ｂ超引导经皮肝穿，将光纤导入肿瘤组织中布点照射。治疗后未见肝功能明显损伤，未出现肝穿出血、腹膜炎等严重并发症，没有一个月内病情恶化者。有１４例患者只作一次治疗，其中５例出院后失访；另９例肿瘤部分缓解率为２２％。１６例患者接受二、三次治疗，肿瘤部分缓解率达到６２％。随访病例中有８例已存活１年以上。     

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.     

点阵组织间照射光动力疗法治疗恶性肿瘤疗效分析

本文报道自1985年以来应用激光光纤点阵组织间照射光动力疗法,治疗口腔颌面部和体表进展期癌37例。结果显示。一次治疗后近期总有效率达100％,其中完全效应占89％,明显效应占11％。对33例完全效应患者随访6年,无瘤生存4年以上12例,其中超过5年的7例。文中讨论了点阵组织间照射光动力疗法的临床意义,分析了疗效影响因素,探讨了综合治疗问题和适应证选择等问题。     

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.     

Photodynamic therapy in the esophagus

Photodynamic therapy (PDT) involves in situ photo-activation of photosensitizers by light at appropriate wavelength, generating highly active singlet oxygen and free radicals. For esophageal mucosal dysplasia such as high-grade dysplasia or intramucosal cancer, curative endoluminal therapy including PDT is now a reality. We review the role of PDT in the esophagus for the past two decades. The light for PDT can be delivered endoluminally freehand by cylindrical diffusers, via inflatable balloon stabilizers or microlens fibers. Porfimer sodium (Photofrin^®) is the only approved photosensitizer for PDT in the esophagus in North America, Europe and Japan. In addition, 5-aminolaevulinic acid (ALA), m-tetra(hydroxyphenyl)chlorin (m-THPC) and benzoporphyrin derivative monoacid ring A (BPD-MA) are other photosensitizers are being evaluated. More randomized clinical trials with long term follow up data are needed to further establish the role of PDT and other endoluminal ablative therapies either on their own or in combination to demonstrate survival benefits, quality of life advantages and cost-effectiveness. Changes in light delivery, timing, dosimetry and new endoscopic devices are needed to possibly improve all aspects of effectiveness. PDT was used mainly for palliation of advanced obstructing cancer of the esophagus at the gastrointestinal junction. More recently, because of the rising detection of the high-grade dysplasia in Barrett’s esophagus, a curative role of PDT in being realized.     

Barrett食管及相关并发症的X线探讨

目的:通过16例经内窥镜及病理证实为Barrett食管的钡餐检查表现,初步探讨Barrett食管及其并发症放射学检查的意义。方法:回顾性分析16例Barrett食管的内窥镜和气钡检查的记录及表现,着重探讨气钡检查的X线表现。结果:食管内窥镜和组织学检查全部病例均有炎症改变,其他可见胃食管反流、食管溃疡和食管腺癌。放射学钡餐检查结果:Barrett食管炎4例,Barrett食管溃疡7例,Barrett食管癌5例。结论:Barrett食管及其并发症至今无明确放射学征象,改进对“Z”线的检查技术和方法,有可能提高其发现率。钡餐发现胃食管反流、食管裂孔疝同时并发食管炎、食管溃疡及食管癌者均应考虑到本症的可能。     

肿瘤光动力学疗法的并发症及其防治

本文重点综述肿瘤光动力学疗法可能发生的并发症及其防治措施，如光敏药物过敏、皮肤光毒性反应、渗出、毛细血管渗漏综合征、空腔形器官穿孔、瘢痕狭窄、感染、出血和其他并发症。     

光动力学疗法净化造血干细胞的研究现状

随着对光动力学疗法（photodynamic therapy，PDT）作用机制的深入研究和新型光敏剂的研发，PDT的应用已经拓展到多种肿瘤性疾病和非肿瘤性疾病的治疗，其中肿瘤性疾病包括皮肤癌、胃癌、食管癌等，而非肿瘤性疾病以鲜红癍痣、年龄相关性黄斑变性、痤疮等为代表。 近年来，PDT行体外造血干细胞净化已成为PDT应用的另一新领域。实验证明PDT能够有效地杀灭多种肿瘤细胞，如白血病细胞、淋巴瘤细胞，且没有细胞周期特异性，对耐药肿瘤细胞同样有效，而对正常造血干细胞损伤轻微。目前应用PDT净化造血干细胞的试验与临床研究正成为国内外学者所关注的热点问题。     

Brain PDD and PDT unlocking the mystery of malignant gliomas

Malignant brain tumours (MBTs) have one of the worst outcomes of human cancers today and their incidence is on the increase. Current treatment failure is usually due to local recurrence of the tumour rather than distant metastasis. In the last three decades we have seen many novel and potentially effective treatment strategies rise rapidly to the rescue. Sadly, however, the majority of these approaches were not good enough to withstand the harsh reality of the sceptical gaze of the scientific eye or the stringent health economics of this millennium. PDD and PDT, however, is one of the few therapies fighting back and still standing today. The results of its randomised controlled trials are eagerly awaited. To date the literature suggests that both PDD and PDT significantly prolong the time to tumour progression, reduce local recurrence, increase radical resection and prolong overall survival of MBTs. PDD and PDT are well tolerated by patients and worthwhile pursuing.     

PDT experience in Brazil: A regional profile

The success of PDT and its establishment into the existent hall of therapeutic modalities depends on the collection of reported experiences from around the world. In that sense, it is important to report approaches taken by different countries and what their views are on the future of PDT. Following this idea, we present our clinical experience in photodynamic therapy (PDT) in Brazil, as well as the experimental advances coming up in parallel with clinical implementation. This report is a consequence of pioneering work in a collaborative program involving the Physics Institute in São Carlos, São Paulo State (SP), Brazil, the Medical School of the University of São Paulo, Ribeirão Preto, SP, Brazil and the Cancer Hospital Amaral Carvalho, Jaú, SP, Brazil. This collaborative program, begun in 1997, with the first patient treated in 1999, has treated over 400 patients by late 2004. About 80% of lesions were located in the head and neck or skin, but experience is being built in esophagus, bladder, gynecology, and cutaneous recurrence of breast cancer, among others. The overall results have shown to be compatible with previously reported data. Modifications, whose goal is to improve patient benefit and optimize results, are being implemented as we gain experience. In parallel with the clinical development, several laboratories have started studying experimental whose purpose is to analyze the clinical results and to contribute to the worldwide effort to bring PDT to the forefront of therapies offered to patients. We present the overall results of our 5 years experience as well as the whole implementation process.     

Clinical PD/PDT in North America: An historical review

The healing properties of light have been appreciated for thousands of years. However, the harnessing of light energy to create a rigorous and reliable means to diagnose and treat human disease is only a relatively recent phenomenon. Despite outstanding results from ancient history and subsequent reemergence and refinement of this knowledge over the last 100 years, it took again the hand of serendipity to open the modern age of Photodiagnosis and Photodynamic Therapy. Based on the prescience and perseverance of a handful, the under appreciated observations of tumor fluorescence and photodynamic action have been brought to a worldwide audience. This review highlights the development of clinical Photodiagnosis and Photodynamic Therapy, emphasizing the significant events and milestones taking place in North America.     

The history of PDT in Norway: Part one: Identification of basic mechanisms of general PDT

Photodynamic therapy (PDT) is now an established treatment of malignant and premalignant dysplasias. A number of first and second generation photosensitizers have been studied in Norway. The aim has been to improve PDT efficiency and applicability. Many critical details regarding the mechanisms of PDT were elucidated by researchers in Norway. In this review we focus on the most important findings related to these basic mechanisms, such as generation of singlet oxygen, estimations of its lifetime, the oxygen effect itself, the subcellular localization of photosensitizers with different properties, their photodegradation during PDT and their tumour selectivity.     

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.     

PD/PDT for gynecological disease: A clinical review

The evolution of diagnostic and interventional procedures for gynecologic disease has led to organ, sexual and reproductive sparing treatments. Photodiagnosis (PD) and photodynamic therapy (PDT) may play a great role for gynecological patients as both offer the potential to achieve these goals.PD/PDT for a wide variety of diagnostic and therapeutic interventions have shown potential for excellent clinical outcomes. However, significant limitations remains, both clinically and dosimetrically, that prevent consistent results. When those limitations are resolved PD/PDT could move to the forefront of gynecological therapy.This clinical review highlights the outcomes and shortcomings of PD/PDT through the peer reviewed literature for gynecological sites.     

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

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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.