Optimal conditions for successful ablation of high-grade dysplasia in Barrett’s oesophagus using aminolaevulinic acid photodynamic therapy

Abstract

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA-PDT) is an attractive alternative to PDT with porfimer sodium for the treatment of high-grade dysplasia (HGD) in Barrett's oesophagus (BO) because of the shorter duration of light photosensitivity and low risk of oesophageal stricture formation. Published results, however, show marked variation in its efficacy, and optimum treatment parameters have not been defined. This study investigated how the dose of ALA and the colour of the illuminating light influenced the biological effect. Twenty-seven patients were enrolled into a randomised controlled trial of red versus green (635 nm or 512 nm) laser light activation for the eradication of HGD with ALA-PDT in Barrett's oesophagus. A further 21 patients were subsequently treated with the most effective regimen. Regular endoscopic follow-up with quadrantic biopsies every 2 cm was performed. The primary outcome measure was eradication of HGD. Patient's receiving ALA at 30 mg/kg relapsed to HGD more than those receiving 60 mg/kg (P = 0.03). Additionally, for those treated with ALA 60 mg/kg, red laser light was more effective than green laser light (P = 0.008). Kaplan-Meier analysis of the 21 patients who were subsequently treated with this optimal regimen demonstrated an eradication rate of 89% for HGD and a cancer-free proportion of 96% at 36 months' follow-up. Using an ALA dose of 60 mg/kg activated by 1,000 J/cm red laser light, we found that ALA-PDT was a highly effective treatment for high-grade dysplasia in Barrett's oesophagus.

ALA PDT for high grade dysplasia in Barrett's oesophagus: review of a decade's experience

“…17,18 It is of historical interest that comparable studies were not performed for porfimer sodium until recently, in an attempt to reduce the incidence of oesophageal strictures. 19 At the start of these studies, all patients were given ALA as a single dose of 30mg/kg dissolved in water, 4 hours before light delivery.…”

Tumor Affinity Photosensitizers for Photodynamic Therapy

“…，消化器内視鏡診断ではバレット食 道腺癌 14) や潰瘍性大腸炎を背景とした colitic cancer 15) などの癌種で PDD への臨床応用への試みがなされてい る．5-ALA を用いた PDT ではバレット上皮の異型上皮 を対象にした海外での報告が散見される 16,17) ． 5. 第三世代の光感受性物質 さらに腫瘍細胞選択性を高め，抗腫瘍効果を向上さ せるべく，優れた第三世代の光感受性物質の開発が行 われている 18) ．それらの多くはキャリアー分子を光感 受性物質に連結したものが多く，キャリアーとしては， monosaccharide 19) , ペプチド (Fig.2 (a) ) ． Hela 細胞での検討では，クロリン単体に比べ，グルコー ス連結クロリン (Glucose conjugated chlorin; G-クロリン) ， Fig.4 Antitumor efffects of G-chlorin PDT against xenograft model of gastrointestinal stromal tumor (GIST).…”

A systematic review of photodynamic therapy in the treatment of pre-cancerous skin conditions, Barrett’s oesophagus and cancers of the biliary tract, brain, head and neck, lung, oesophagus and skin

“…97 In a small trial comparing ALA with red or green light, there were no major complications. 105 Differences in fever and sudden death were not significant between PDT and APC groups in one trial.…”

“…Two of the three additional trials to be discussed in this section were reported as a full paper, 102,105 while the other was reported as an abstract only.…”