Endoscopy Photodynamic Therapy
Photodynamic therapy (PDT) has lost importance in daily clinical practice during recent years. In Barrett’s oesophagus it has involved a variety of agents, including porfimer sodium and 5-aminolevulinic acid (5-ALA).19–21
Only sodium porfimer is available in the US, whereas 5-ALA is more often used in Europe.
PDT has several disadvantages leading to a dramatic decrease in its use: PDT with porfimer sodium is expensive and associated with a high complication rate. Photosensitivity and stricture formation may occur in up to 30% of patients. The use of 5-ALA appears to be associated with considerably fewer complications and has shown promising results. Nevertheless, given the advent of other techniques with a more favourable side effect profile, PDT appears to have only a limited role today.
Radiofrequency Ablation
In recent years, in most centres PDT has been replaced by RFA of Barrett’s epithelium . Simultaneously, the role of APC has decreased, even though APC is still used especially in short-segment Barrett’s oesophagus. RFA involves the application of high-power radiofrequency energy using bipolar electrodes, causing rapid heating of the tissue with ablation to a depth of approximately 0.5mm. A balloon catheter 3cm in length with circular electrodes delivering the energy designed for circumferential ablation (HALO-360) is used for long segments of Barrett’s epithelium. A focal device (HALO-90) that fits over the tip of the endoscope can be used for ablation of smaller areas.
In a US multicentre registry with 16 centres, the safety and efficacy of RFA in patients with HGIN in Barrett’s oesophagus were investigated.22 One hundred and forty-two patients were included. Strictures occurred in only one patient and no buried glands were found during follow-up. Out of the 92 patients with at least one follow-up endoscopy, complete removal of HGIN was confirmed in 90.2%. However, only 54.3% of Barrett’s epithelium could be successfully eradicated.
A large prospective randomised sham controlled trial investigated the efficacy of RFA in 127 patients with LGIN (n=63) and HGIN (n=64) from 19 US centres.23
Patients were 2:1 randomised to RFA or sham treatment. The one-year analysis demonstrated that 74% of patients randomised to RFA achieved complete clearance of Barrett’s metaplasia compared with 0% in the sham arm.
Two recently published studies from the Amsterdam group combined ER of visible neoplastic lesions with circumferential and focal RFA of the remaining Barrett’s oesophagus containing HGIN in 23 patients.24,25
Endoscopic Resection
In general, it can be recommended to replace the term ‘endoscopic mucosal resection’ with ‘endoscopic resection’, which is now widely used. This change derives from the fact that during the procedure, not only the mucosa, but also the submucosal layer is resected.
Complete remission was achieved in 99% of cases, and the calculated five-year overall survival rate was 98%. None of the patients died of Barrett’s neoplasia, and metachronous lesions were observed in 11% after a mean of 36.7 months.
This study of ER in a highly selected cohort of patients with low-risk Barrett’s carcinoma does not reflect the general population of patients with Barrett’s neoplasia, but clearly demonstrates the safety and efficacy of the method in an expert centre. The results in terms of the complete response rate and recurrence rate are not quite as good in a general patient population with HGIN and mucosal Barrett’s cancer, with the majority not fulfilling the low-risk criteria.27,28
The largest series so far on endoscopic treatment of early Barrett’s neoplasia in 349 patients was published recently by our group.28
We
Ablation without prior ER was performed in 10 patients with flat HGIN. Complete elimination of neoplasia and Barrett’s metaplasia was possible in all of the 23 included patients and none of the 836 biopsies of the neo-squamous mucosa contained sub-squamous Barrett’s oesophagus.
RFA seems to provide a high rate of complete Barrett’s eradication without residual Barrett’s mucosa underneath the newly developed squamous epithelium (buried glands). In addition, the complication rate seems to be very low, especially compared with PDT. RFA seems to be an effective adjunct to ER for ablation of the remaining non-dysplastic Barrett’s epithelium after successful resection of all localisable HGIN and adenocarcinoma.
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treated 61 patients with HGIN and 288 with mucosal adenocarcinoma. ER was performed in 279 patients, PDT with 5-ALA as a photosensitiser in 55 patients and both methods were combined in 13 patients for treatment of neoplastic Barrett’s oesophagus. Treatment was highly effective with a remission rate of 96.6%. However, during a follow-up of more than five years, metachronous and recurrent neoplasia was observed in 21.5% of cases. Most patients were re-treated successfully and long-term complete response was achieved in 94.5%. Long-term survival of patients treated for Barrett’s neoplasia in this series did not significantly differ from that of the normal German population with the same age and gender distribution.
Those results clearly demonstrated that ER is safe and effective in patients with HGIN and mucosal Barrett’s cancer up to five years of
EUROPEAN GASTROENTEROLOGY & HEPATOLOGY REVIEW
Until recently, few studies with large patient numbers or long follow-up were available for ER. A recent study by our group has now provided excellent long-term results for ER in 100 consecutive patients with low-risk mucosal Barrett’s cancer (lesion diameter <20mm and macroscopically type I (polypoid), IIa (flat and slightly elevated), IIb (flat and level) or IIc (flat, depressed <10mm); well- or moderately differentiated histological grade; lesions limited to the mucosa proven by histology of the resected specimens; and no invasion of lymph vessels or veins).27
Only the removal of all neoplastic lesions by ER provides specimens that can be evaluated by the pathologist in terms of infiltration depth and risk factors for lymphatic spread to prevent undertreatment. Afterwards, ablation of the non-dysplastic Barrett’s mucosa can significantly reduce the rate of metachronous neoplasia or recurrences. Pouw et al. treated 16 patients with adenocarcinoma and seven patients with HGIN in the EURO-I study.26
ER was performed
for all visible lesions followed by RFA of the remaining Barrett’s segment. Neoplasia and intestinal metaplasia were eradicated in 95 and 88% of patients.
As with ablative techniques other than ER, RFA does not allow tissue confirmation of efficacy, leaving a measure of uncertainty for each patient. Therefore, an ablative treatment method should never be chosen as the primary treatment tool for neoplasia in Barrett’s oesophagus, such as HGIN or early cancer.
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