C. J. Stoddard

Photodynamic therapy for dysplastic Barrett's oesophagus: a prospective, double blind, randomised, placebo controlled trial

BACKGROUND AND AIMS Photodynamic therapy (PDT) is a treatment in which cell damage is achieved by the action of light on a photosensitising agent. We have assessed the potential use of PDT in the ablation of Barretts oesophagus. METHODS Thirty six patients with dysplastic Barretts oesophagus receiving acid suppression medication with omeprazole were randomised to receive oral 5-aminolaevulinic acid (ALA) 30 mg/kg or placebo, followed four hours later by laser endoscopy. Follow up endoscopy was performed at one, six, 12, and 24 months. RESULTS Of 18 patients in the ALA group, a response was seen in 16 (median decrease in area in the treated region 30%; range 0–60%). In the placebo group, a decrease in area of 10% was observed in two patients with no change in 16 (median 0%; range 0–10%; treatment vplacebo, p<0.001). No dysplasia was seen in the columnar epithelium within the treatment area of any patient in the PDT group. However, in the placebo group, persistent low grade dysplasia was found in 12 patients (p<0.001). There were no short or long term major side effects. The effects of treatment were maintained for up to 24 months. CONCLUSIONS This is the first randomised controlled trial of PDT for Barretts oesophagus. It demonstrates that ALA induced PDT can provide safe and effective ablation of low grade dysplastic epithelium.

Endoscopic ablation of Barrett's oesophagus: a randomized‐controlled trial of photodynamic therapy vs. argon plasma coagulation

Background : Barretts oesophagus is the major risk factor for oesophageal adenocarcinoma. 5‐Aminlevulinic acid‐induced photodynamic therapy and argon plasma coagulation have been shown to be effective for ablating Barretts oesophagus, but a comparative trial of these two modalities has not been reported.

Ablation treatment for Barrett oesophagus: what depth of tissue destruction is needed?

AIM: To establish the depth of Barretts columnar epithelium and normal squamous oesophageal epithelium, in order to determine the depth of destruction required in ablation treatment for Barrett oesophagus. METHODS: Histological specimens from 100 cases of Barrett oesophagus and 100 samples of normal squamous oesophageal epithelium were studied. Using a system of multiple measurements until the change in cumulative mean values varied by less than 5%, the overall mean and normal range of depth was calculated for each type of epithelium. RESULTS: Barrett columnar epithelium is minimally thicker (mean (SEM) 0.50 (0.004) mm; range 0.39 to 0.59 mm) than normal squamous epithelium (0.49 (0.003) mm; 0.42 to 0.58 mm), although this difference is probably too small to be of clinical relevance. CONCLUSIONS: Although there are numerous clinical reports of various methods of ablation treatment for Barrett oesophagus, little attention has been paid to the depth of tissue destruction required. This is the first study to look specifically at this issue, and it provides information on the necessary depth of epithelial ablation.

5-Aminolevulinic acid photosensitization of dysplastic Barrett's esophagus: a pharmacokinetic study.

Photodynamic therapy (PDT) using 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) may have a role in the treatment of dysplastic Barretts esophagus. Before ALA‐induced PDT can be used clinically, optimum treatment parameters must be established. In this study of 35 patients, the issues of drug dosage, time interval between drug and light delivery and side effects of oral ALA administration are addressed. Spectrofluoro‐metric analysis of tissue samples demonstrates that oral ALA administration induces porphyrin accumulation in esophageal tissues, with maximum levels at 4–6 h. High‐performance liquid chromatography confirms the identity of this porphyrin as PpIX, and fluorescence microscopy analysis demonstrates that it preferentially accumulates in the esophageal mucosa, rather than in the underlying stroma. Side effects of ALA administration included malaise, headache, photosensitivity, alopecia, transient derangement of liver function, nausea and vomiting. Fewer side effects and less hepatic toxicity was seen with 30 mg/kg than 50 mg/kg ALA. In conclusion, oral ALA administration induces preferential PpIX accumulation in the esophageal mucosa, with peak PpIX fluorescence noted at 4 h and minimal systemic toxicity at a dose of 30 mg/kg.

Colonic myoelectrical activity in man: comparison of recording techniques and methods of analysis.

Both monopolar and bipolar recordings of human colonic myoelectrical activity have been made on 29 occasions from implanted serosal electrodes attached to either the ascending colon or transverse colon. Visual and computer analysis of the signals were made and the incidences of the two electrical rhythms present in the colon were compared for the two recording techniques, recording sites, and methods of analysis. The percentage incidence of both rhythms was similar for the mono and bipolar recording techniques in both parts of the colon. The incidence of the two rhythms in the transverse colon was approximately twice that recorded in the ascending colon, this being true for both recording techniques and methods of analysis, but neither was detected for more than 50% of the time. It is concluded that the methods of data analysis probably account for the differing incidences of electrical activity in the human colon that have been reported previously.

The immediate and delayed effects of different types of vagotomy on human gastric myoelectrical activity.

The immediate and delayed effects of different types of vagotomy on the antral myoelectrical activity have been studied in 52 patients who had previously undergone either highly selective vagotomy (HSV) or truncal vagotomy and pyloroplasty (TV + P) for the treatment of chronic duodenal ulceration up to eight years previously. The frequency of the electrical activity was not statistically different between the two types of operation. After HSV the triphasic waveshape of the antral myoelectrical activity was retained; it was recorded more frequently in the delayed tests (98.0 plus or minus 1-7%) of the recording period than in immediate tests (74-7 plus or minus 6-5%) whereas mean amplitude in the immediate tests (1-59 plus or minus 0-13 mV) was not significantly changed in the delayed tests (1-49 plus or minus 0-08mV). After TV + P the waveform was more sinusoidal in shape, being recorded more often in the delayed tests (91-7 plus or minus 2-7%) than in the immediate tests (41-4 plus or minus 8-9%) although the mean amplitude between the immediate (0-090 plus or minus 0-06 mV) and delayed tests (0-94 plus or minus 0-07 mV) was not significantly different. The only significant change in the myoelectrical activity with the passage of time after vagotomy was an increase in the percentage activity.

The effects of varying the extent of the vagotomy on the myoelectrical and motor activity of the stomach

The effects of varying the extent of vagotomy on the myoelectrical and motor activity of the stomach have been successfully studied in 21 patients undergoing either truncal, selective, or highly selective vagotomy for the treatment of chronic duodenal ulceration. The mean percentage time that regular antral myoelectrical activity was recorded preoperatively was 95·8% ± 1·0 and this was decreased following highly selective vagotomy (74·0% ± 6·6), selective vagotomy (37·8% ± 12·4), and truncal vagotomy (30·2% ± 10·4). The mean amplitude of the pacesetter potential was less following truncal (0·86 mV ± 0·05), selective (1·32 mV ± 0·09), and highly selective vagotomy (1·67 ± 0·09) than in preoperative studies (2·21 mV ± 0·12). Following truncal and selective vagotomies the triphasic waveform of the pacesetter potential changed to a sinusoidal shape. No significant change in the mean preoperative frequency of the myoelectrical activity (3·03 cpm ± 0·08) occurred after vagotomy. Thus the changes in the electrical activity of the stomach are related to the extent of the vagal denervation. Intravenous administration of insulin did not alter these patterns except after highly selective vagotomy when the amplitude of the electrical waves, the incidence of action potentials, and percentage motor activity were increased.

Use of autoregressive-modelling techniques for the analysis of colonic myoelectrical activity in man

Monopolar and bipolar recordings of human colonic myoelectric activity have been made on 29 occasions from implanted serosal electrodes attached to either the ascending colon or transverse colon. The records were analysed visually by fast-Fourier-transform techniques and by autoregressive modelling. The results obtained by autoregressive modelling, which is a completely objective technique, were compared with the results obtained by visual and fast-Fourier-transform techniques. It is concluded that the autoregressive-modelling technique gives results which correlate well with visual analysis by a trained observer, and has the advantage of a numerical print out of frequency together with automatic significance detection. The technique would enable accurate comparison of results to be made by research groups working on colonic myoelectrical activity.