内镜分子影像技术诊断Barrett食管及其相关性肿瘤的研究进展

Barrett食管是食管下段复层鳞状上皮被化生的单层柱状上皮所替代的一种病理现象,可伴或不伴肠上皮化生[1].在欧美国家食管腺癌的发病率呈快速上升趋势,Barrett食管是食管腺癌的重要危险因素,因此对Barrett食管及其早期病变的早发现、早诊断及早治疗是降低食管腺癌发病率的有效措施.目前,诊断Barrett食管的主要方法是白光内镜检查结合组织病理学活检,但内镜检查时容易漏诊,且随机活检会漏掉大约50％的病变组织[2-4].因此,急需一种新的技术来解决这个问题,而分子影像学是一种新的诊断手段.     

经内镜射频治疗Barrett食管73例临床分析

Barrett食管（Barrett＇s esophagus，BE）是指食管下段的复层磷状上皮被有肠化的单层柱状上皮所替代的一种病理现象，又名柱状上皮细胞食管。Barrett食管是一种癌前病变状态，其发生食管癌的危险性较一般人群高30～50倍，发生率为每年1／150。此类患者一般需终身内镜监测以早期检出食管腺癌，提高存活率。现行的治疗方法主要是抑酸药物治疗和外科食管切除术，但前者只能控制反流症状，不会减少发生癌变的危险性，后者有一定的手术致死率、手术并发症及手术禁忌证。我科自2002～2004年于内镜下经射频治疗Barrett食管73例。现将结果报告如下。     

光敏剂分子信标的研究与应用进展

光动力疗法(Photodynamic Therapy,PDT)是一种联合利用光、光敏剂和氧分子,通过光动力反应选择性地治疗疾病的靶向疗法。光敏剂作为PDT的关键要素之一,其性能直接决定着PDT的疗效。笔者首先介绍了应用于PDT的光敏剂分子信标(photosensitizer molecular beacons,PMB)的基本原理,重点分析和总结了PMB中特异性肽链、淬灭基团和光敏剂等组分的研究进展。最后展望了PMB的发展趋势和潜在应用前景。     

光动力疗法在宫颈上皮瘤变中的应用

目的:本研究系统分析了光动力疗法(photodynamic therapy,PDT)治疗宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)的疗效和安全性。方法:通过对Pubmed及中国知网中涉及的相关文献以及2012年8月至2017年12月,笔者采用PDT治疗宫颈上皮瘤变的情况进行分析和总结。结果:局部和系统给药途径的光敏剂均可用于宫颈上皮瘤变的PDT治疗,系统给药方式采用的光敏剂主要为Photofrin和血卟啉注射液,局部给药方式采用的光敏剂5-氨基酮戊酸(ALA)为主,亦可使用氨基酮戊酸甲酯(MAL)、氨基己糖酮戊酸(HAL)、dihematoporphyrin ether(DHE)等。PDT照射光源通常采用波长630～635 nm的红光,多种PDT治疗光参量被用于CIN的治疗。基于局部用光敏剂的PDT疗法治疗主要用于CINⅠ～Ⅱ级的治疗,其有效率为50%～95%,基于系统用光敏剂的PDT疗法主要用于CINⅡ～Ⅲ级的治疗,其有效率为CR 88%～100%。基于局部和系统用光敏剂的PDT疗法对宫颈结构和机能均有较好的保护作用。结论:PDT治疗宫颈上皮内瘤变是一种安全、有效的方法,但局部和系统两种给药方式的PDT治疗的疗效比较还需进行大样本的研究,从而对PDT治疗的光参量进行优化。     

类风湿性关节炎的光动力学疗法

类风湿性关节炎(rheumatoid arthritis,RA)是一种以关节滑膜炎症为主要病理变化的自身免疫性疾病,如不及时治疗病变会继续加重甚至致残.光动力学疗法(photodynamic therapy,PDT)是近几年兴起的治疗RA的新颖疗法,作为一种选择性杀伤病变组织而不伤及正常组织、创伤小的新型疗法,有着广泛的发展前景.笔者简述PDT的原理,着重综述PDT治疗RA可用的光敏剂和PDT治疗条件的优化.     

光声敏化剂在光动力疗法与声动力疗法中的作用研究

正近年来,针对癌症的治疗出现了两种新方法,光动力疗法(PDT)和声动力疗法(SDT)。两者都是光敏剂(声敏剂)和物理手段相结合的治疗方法。PDT是指向机体内注入光敏剂,通过血液到达病灶组织,光敏剂在一定波长激光照射下,吸收能量发生光化学反应,产生活性单线态氧将肿瘤细胞杀死。PDT与传统的治疗手段相比具有选择性高、不良反应小的优点,此外光敏剂本身无毒副作用,机体不会产生抗药性。目前PDT在临床上用于多种疾病的治疗,包括肿瘤、     

凋亡相关基因与肿瘤光动力学疗法的疗效

光动力学疗法(PDT)是指利用光敏剂和光治疗肿瘤的一种非手术疗法,于20世纪70年代开始应用于人类肿瘤的治疗.随着对PDT作用机制及影响疗效因素的深入研究,凋亡相关基因的表达和PDT疗效的关系尤为引人关注.本文综合了国内近年在此方面的研究动态,着重讨论科凋亡相关基因及其与PDT疗效的关系,并对PDT诱导肿瘤细胞凋亡或坏死做一概述.     

两种光敏剂对鲜红斑痣光动力学疗法的疗效影响

目的 评价两种光敏剂对鲜红斑痣的光动力学疗法(PDT)疗效的影响,进一步评价该疗法治疗鲜红斑痣的有效性和安全性.方法 根据就诊顺序,将30例鲜红斑痣患者随机分成两组,每组15例,进行PDT,一组接受癌光啉(PSD-007),另一组接受血卟啉单甲醚(HMME),3个疗程后总结分析两种光敏剂对疗效的影响.结果 治疗3个疗程后,PSD-007组的患者完全治愈率为33.3%,明显高出HMME组的6.7%;显效率前者为100%,而后者仅为80%.结论 PSD-007作为光敏剂的光动力学疗法的疗效优于HMME-PDT;PDT治疗鲜红斑痣的疗效可靠、安全性好,值得临床进一步推广.     

光动力疗法治疗银屑病的研究进展

光动力疗法（photodynamic therapy,PDT）是建立在光敏剂基础上的治疗方法。当用特定波长的光照射,产生大量的活性氧物质,从而造成细胞的损伤和死亡,以达到治疗目的。早期PDT在皮肤科主要用于肿瘤的治疗并取得疗效,新近研究者应用PDT治疗银屑病,也取得一定疗效。然而尚需大量的比较性研究以及PDT治疗方案的优化以确定PDT在银屑病治疗中的地位。     

光动力治疗三要素及肿瘤光动力治疗后复发问题的探索

光动力疗法(photodynamic therapy,PDT)是一种联合利用光敏剂、光和氧,通过光动力反应选择性地治疗肿瘤的局部靶向疗法。光敏剂、激光和氧是光动力疗法的三个重要元素,本文主要从PDT的三要素及PDT后肿瘤复发进展的原因进行了综述。     

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 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's esophagus: diagnosis by double-contrast esophagography

A blinded, retrospective study was performed to determine the role of double-contrast esophagography in diagnosing Barrett's esophagus. The study group consisted of 200 patients who had double-contrast esophagrams and endoscopy because of severe reflux symptoms. The radiographs were reviewed by two gastrointestinal radiologists who had no knowledge of the endoscopic findings. Patients were classified as being at high risk for Barrett's esophagus if the radiographs revealed a high stricture or ulcer or a reticular mucosal pattern; at moderate risk if the radiographs revealed a distal peptic stricture and/or reflux esophagitis; and at low risk if none of the aforementioned findings were present. When these radiologic criteria were used, 10 patients (5%) were thought to be at high risk, 73 (37%) at moderate risk, and 117 (58%) at low risk for Barrett's esophagus. Endoscopic correlation revealed biopsy-proved Barrett's mucosa in nine (90%) of 10 patients at high risk, in 12 (16%) of 73 at moderate risk, and in only one (1%) of 117 at low risk for Barrett's esophagus. Thus, endoscopy is clearly indicated for patients in the high-risk group. Because of the lower prevalence of Barrett's esophagus in the moderate-risk group, clinical judgment should be used in deciding when to perform endoscopy in these patients. However, most patients were in the low-risk group, and the prevalence of Barrett's esophagus was so low in this group that endoscopy does not appear to be warranted. Thus, the major value of double-contrast esophagography is its ability to separate patients into high-, moderate-, and low-risk groups for Barrett's esophagus to determine the relative need for endoscopy and biopsy.     

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.     

Bare fiber photodynamic therapy using porfimer sodium for esophageal disease

During Digestive Disease Week 2005 in Chicago, Illinois, our group of 10 gastrointestinal photodynamic therapists met to discuss variations in procedural technique and treatment protocols. An extensive review of the use of photodynamic therapy (PDT) for esophageal disease has recently been published elsewhere [Wolfsen HC. Present status of photodynamic therapy for high-grade dysplasia in Barrett's esophagus. J Clin Gastroenterol 2005;39(3):189–202]. This report, based mostly on clinical experience and common sense rather than evidence-based medicine, is a detailed discussion of pragmatic issues. In summary, our centers treat patients with Barrett's dysplasia, Barrett's or squamous cell carcinoma using the photosensitizer porfimer sodium (2 mg/kg total body weight) and bare fiber PDT (no fiber centering devices). Aggressive suppression of gastric acid is uniformly emphasized. The most common technique variables were the light energy source, light dosimetry and the amount of Barrett's mucosa treated during a course of PDT. Standardization of porfimer sodium PDT procedures and light dosimetry may enhance treatment outcomes.     

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.     

Efficacy of radiologic studies in the detection of Barrett's esophagus

Esophageal radiography using two different air-contrast techniques was used to examine 30 patients with Barrett's esophagus and 18 controls. All patients had upper gastrointestinal endoscopy and biopsy of the esophagus. The radiographs were randomized, masked, and then interpreted by two radiologists blinded to the endoscopic and biopsy diagnosis. Depending upon the diagnostic strategy of the radiologist, sensitivity varied from 0.36 to 0.83 and specificity from 0.56 to 1.00. A typical receiver-operating-characteristic curve was generated. Esophageal radiography is effective in identifying those patients who have stricture and ulceration as a complication beyond the epithelial transformation. However, because of low sensitivity, it is not a satisfactory method for identifying most cases of Barrett's esophagus.     

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.     

肿瘤光动力疗法：理论基础及治疗策略

肿瘤的传统治疗方案主要包括手术治疗、放疗及化疗等,而光动力疗法（Photodynamic therapy,PDT）是肿瘤治疗领域内一项新的、引人注目的方法。它的基本过程是利用特定波长的光照射选择性蓄积在病变处的光敏剂,光敏剂随之活化并与氧分子作用产生具有细胞毒性的单线态氧及活性氧物质,经过直接与间接作用最终导致肿瘤细胞死亡。光动力疗法治疗肿瘤副作用小,对实体肿瘤尤其是浅表性肿瘤,如皮肤基底细胞癌等有着良好的治疗效果。光敏剂、光及组织氧是现代光动力疗法概念的重要组成部分。本文回顾并综述了光动力疗法的理论基础及治疗策略。     

Barrett's esophagus and its relationship to cancer.

The authors present an overview on the current status of Barrett's esophagus. Pathogenesis, histological classification, prevalence, and incidence regarding relationship to adenocarcinoma frequency are described. The accuracy of endoscopic diagnosis and the role of radiology for an optimal high risk patient's screening program are discussed according to the author's experience.