Patients Undergoing Photodynamic Therapy for Barrett’s Dysplasia

Results

Treatment Results: Effect of Gender and Barrett's Segment Length

We have treated 102 consecutive patients with Barrett's HGD or mucosal adenocarcinoma with a median follow-up of 1.6 years (range: 0.5-6.5; Table 1). All patients were treated with a single course of PDT and complete ablation of Barrett's glandular epithelium has been confirmed in a majority of patients (56%; 57 patients). In the remaining patients, any residual Barrett's mucosa was thermo ablated at follow-up endoscopy using an argon beam coagulator. While most of our patients are elderly men, our study included a larger number of women compared with previous studies that typically include around 10% women.[12,13] There appeared to be no significant differences between men and women with regards to age, Barrett's segment length, treatment outcome (complete ablation of glandular epithelium), stricture rate or follow-up time. Mucosal adenocarcinoma patients had lengths of Barrett's glandular epithelium that were significantly shorter than those in patients with HGD. Mucosal adenocarcinoma patients experienced a higher success rate of complete Barrett's ablation (76% vs. 52% for Barrett's HGD patients) but this difference did not reach statistical significance (P = 0.07; Table 2).Barrett's Dysplasia and Carcinoma Detection at Surveillance vs. Index Endoscopy

Only a slight majority of patients (55 patients; 54%) were referred from endoscopy surveillance programmes where these patients had been monitored for Barrett's disease over a median of 5 years. Most of these patients (39 patients; 89%) had symptoms of chronic acid reflux disease. The remaining 47 patients referred for endoscopic ablation therapy had been diagnosed at their index endoscopy with Barrett's dysplasia or carcinoma without a prior diagnosis of Barrett's dysplasia (Table 3). Most of these patients presented with non-reflux-related symptoms including gastrointestinal bleeding, chest pain and dysphagia (Table 4). The length of the Barrett's segment was significantly longer (median 5 cm, range: 1-16) for surveillance patients compared with those diagnosed on index endoscopy (median 3 cm, range: 1-10, P < 0.001). There was no difference in the oesophageal vs. non-oesophageal symptoms between surveillance and index endoscopy patients.Complications Associated With Photodynamic Therapy

Treatment complications are summarized in Figure 1. Oesophageal stricture requiring dilation occurred in 20% of patients who underwent a median of five dilation procedures to restore stable lumen patency. These strictures generally have the endoscopic appearance of blanched, thickened, inelastic mucosa similar to strictures related to external beam radiation. Dilations were performed in the usual manner with Savary or American dilators over a guidewire, with or without the use of fluoroscopic guidance. Tight post-PDT strictures tend to reform rapidly so repeat dilation is performed at short intervals (every 10-14 days) until a stable lumen is established. Photocutaneous toxicity (severe sunburn-like reactions) occurred in 18% of patients related to inadvertent exposure to sunlight especially within the first 2 weeks after treatment when cutaneous porfimer sodium concentrations are highest. All patients responded to medical therapy (typically a short course of oral corticosteroids), none required hospitalization and there have been no long-term sequelae. Cardiovascular complications occurred in two patients. One man with Barrett's HGD developed new onset atrial fibrillation after receiving PDT to a 15 cm Barrett's segment. Cardiac evaluation found no significant underlying coronary artery disease and PDT-associated inflammation and irritation of the left atrium adjacent to the proximal oesophagus was the presumed cause of atrial fibrillation. He was given oral anticoagulant therapy on an out-patient basis and converted spontaneously to normal sinus rhythm. Five years later, he has had no further problems with cardiac dysrythmias. The other patient had significant coronary artery disease and history of heart failure. After PDT delivery to a 12 cm Barrett's segment, she developed recurrent congestive heart failure that required hospitalization and medical treatment. She recovered uneventfully with medical treatment. Oesophageal perforation occurred in one man treated for a 7 cm segment Barrett's HGD who developed severe chest pain within 2 days after PDT. The physical examination was otherwise unchanged and he did not manifest haemodynamic instability or cardiopulmonary symptoms. Contrast oesophageal radiography found no sign of perforation but CT documented free air in the chest and abdomen implicating a transient perforation at the gastro-oesophageal junction probably related to vomiting. Admitted for observation, bowel rest and antibiotics, his symptoms completely resolved during a 1-week hospitalization, without the need for surgery. Overall, complications occurred in 41% of patients.

Figure 1. (click image to zoom) Percentage of patients with serious adverse events associated with photodynamic therapy (PDT). Oesophageal strictures requiring dilation occurred in 20% of patients and photosensitivity-requiring intervention occurred in 18%. There were two patients with a cardiac complication (one with new onset atrial fibrillation and one with an exacerbation of congestive heart failure). Finally, there was one oesophageal perforation that resolved without surgical intervention.

Incomplete ablation of Barrett's neoplasia occurred in four patients (4%). Despite our intensive surveillance endoscopy protocol, we have not found residual subsquamous glands in any other patients. In three of these patients, the residual disease was detected within 8 weeks of PDT at follow-up surveillance endoscopy when biopsies taken throughout the segment of previously treated Barrett's segment documented subsquamous glandular HGD or carcinoma. Argon plasma coagulation, therefore, was not utilized in any of these patients. Neither CT nor EUS detected mucosal or para-oesophageal abnormalities. Subsequently, oesophagectomy successfully resected the oesophageal intramucosal disease without evidence of submucosal disease and no sign of lymph node involvement. The fourth patient had previously undergone endoscopic mucosal resection elsewhere documenting intramucosal carcinoma with extensive thermal cautery effect limiting evaluation of deeper tissue layers. However, CT and EUS documented abnormal oesophageal lymphadenopathy 8-12 weeks after PDT. Despite chemoradiation therapy and oesophagectomy, as described below, the patient developed metastatic adenocarcinoma.

Previous PageSection 3 of 4Aliment Pharmacol Ther 20(10):1125-1131, 2004. © 2004 Blackwell Publishing
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