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A study is conducted with the aim to compare 5-aminolevulinic acid induced photodynamic therapy (ALA-PDT) with argon plasma coagulation (APC) with respect to complete reversal of BarrettEs oesophagus (BO). The administration of APC or ALA-PDT in combination with APC in multiple treatment sessions results in complete reversal of BarrettEs epithelium in nearly two third of the patients.

Background: Data on cancer risk in patients with long-segment Barrett's oesophagus (BO) from older studies are often difficult to interpret, since the definition of BO has evolved from an endoscopical to a histological diagnosis. In this work the diagnoses in the Rotterdam BO cohort on current standards was redefined to obtain more accurate data on cancer risk in patients who had not undergone standard endoscopic surveillance. In addition, it was determined which patient factors present at index endoscopy were associated with neoplastic progression in BO. Methods: The Rotterdam BO cohort comprises all patients with ≥3 cm BO, diagnosed at endoscopy between 1973 and 1984. In the present study, only patients with intestinal metaplasia were included ( n = 105). Follow-up data were obtained by questionnaires and/or interviews with patients or treating physicians. A Kaplan-Meier analysis was used to estimate 20-year risks. Results: The mean length of the BO was 7.1 cm (range: 3-15 cm). Cancer in BO developed in 6/105 (6%) patients, and high-grade dysplasia (HGD) in 5/105 (5%) patients during 1329 patient-years of follow-up, which equals one cancer case per 221 patient-years and one HGD case per 266 patient-years. After a mean follow-up of 12.7 years, 72 (69%) patients had died; only 4 of them died of oesophageal cancer or its treatment. A longer length of BO was associated with an increased risk of progression to HGD or cancer ( P < 0.02). Six of 24 patients who ever had low-grade dysplasia progressed to HGD or cancer 2-16 years after a diagnosis of BO. Conclusions: The annual risk of developing HGD or adenocarcinoma in patients with long-segment BO is 0.83%. Death due to adenocarcinoma is, however, uncommon, even in a cohort of patients with long-segment BO. [ABSTRACT FROM AUTHOR]

5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis, which is used for ALA-based photodynamic therapy (ALA-PDT), was studied in tissues of 10 patients with Barrett's oesophagus (BE) and adenocarcinoma of the oesophagus (AC) undergoing oesophagectomy at a mean time interval of 6.7 h after the ingestion of ALA (60 mg kg(-1)). In BE, AC, squamous epithelium (SQ) and gastric cardia, the activities of the haem biosynthetic enzymes porphobilinogen deaminase (PBG-D) and ferrochelatase (FC) and the PDT power index--the ratio between PBG-D and FC in BE and AC in comparison with SQ--were determined before ALA ingestion. Following ALA administration, ALA, porphobilinogen, uroporphyrin I and PPIX were determined in tissues and plasma. The PDT power index did not predict the level of intracellular accumulation of PPIX found at 6.7 h. In BE, there was no selectivity of PPIX accumulation compared to SQ, whereas in half of patients with AC selectivity was found. Higher haem biosynthetic enzyme activities (i.e. PBG-D) and lower PPIX precursor concentrations were found in BE and AC compared to SQ. It is therefore possible that PPIX levels will peak at earlier time intervals in BE and AC compared to SQ. [ABSTRACT FROM AUTHOR]

Reduced expression of E-cadherin, a cell-cell adhesion molecule, is observed in oesophageal adenocarcinomas and correlates with less favourable pathological parameters and survival. To determine if genetic events lead to reduced E-cadherin expression in these patients, we screened all 16 exons of the E-cadherin gene for mutations with the polymerase chain reaction single-strand conformation polymorphism analysis (PCR-SSCP) technique in 49 resection specimens, including four loco-regional lymph node metastases, four established cell lines and four xenografts. Fifteen exon-spanning primer pairs were used, and in nine amplicons aberrant bands were detected. Sequencing of the amplicons revealed a one base-pair deletion (codon 120; exon 3) in cell lines JROECL 47 and JROECL 50 leading to a premature downstream stop codon. Polymorphisms were identified for amplicons 1, 4/5, 11, 12, 13, 14 and 16 corresponding with data from the literature. Three new polymorphisms were detected for amplicons 2, 3 and 4/5. Loss of heterozygosity (LOH) of the E-cadherin locus on 16q22.1 was examined with four polymorphic markers. LOH was found in 31 of the 48 informative cases (65%). These results show that, despite the frequent LOH of the E-cadherin locus, mutations in the E-cadherin gene are rare events and can not be held responsible for down-regulation of E-cadherin observed in the majority of adenocarcinomas of the oesophagus. [ABSTRACT FROM AUTHOR]