Background Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. Methods Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. Results Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P Ͻ 0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses, as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P ϭ 0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P ϭ 0.01). Conclusions Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.

Chylothorax is an uncommon complication of oesophagectomy. In a review of 537 oesophageal resections there were 11 cases of chylothorax, an incidence of 2.0 per cent. There was no correlation with site, size, penetration, lymph node status, length or type of tumour but there was a significant correlation between chylothorax and the type of operative procedure carried out. The incidence in 95 transhiatal resections was 10.5 per cent. The incidence following 442 transthoracic procedures was 0.2 per cent (P less than 0.001) with one chylous fistula occurring after a three-stage oesophagectomy. Initial management was conservative with chest drainage and total parenteral nutrition. Thoracotomy and duct ligation was subsequently carried out in three patients and was successful in two. The third patient died. Conservative management alone was successful in four out of eight patients, with closure of the fistula at a median of 35 days (range 14-42 days). Four patients treated conservatively died. Transhiatal oesophagectomy greatly increases the risk of chylothorax, a condition that carries a high mortality rate (46 per cent in this series) whether managed conservatively or by surgical intervention.

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.

Fasting and postprandial intragastric bile acid concentrations have been estimated and compared in patients with complications of Barrett's oesophagus, patients with Barrett's oesophagus without complications, patients with oesophagitis and a group of normal subjects who acted as controls. There was no significant difference in fasting intragastric bile acid concentrations between the groups. Postprandial bile acid concentrations were significantly greater in the patients with complications of Barrett's than in the remaining groups at 60, 90 and 120 min. Significant concentrations of bile acids were seen in gastric juice of unaltered pH and may be undetected on intra-oesophageal pH monitoring. Duodenogastric reflux may be implicated in the pathogenesis of complications of Barrett's oesophagus.

SUMMARYThe proinflammatory cytokines play a central role in mediating cellular and physiological responses, and levels may reflect immune system effectiveness. In this study, the effect of ageing on the inflammatory response was examined using a novel method to detect production of the proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-a), IL-6 and IL-1b. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors of different ages were incubated for 0, 24, 48 and 72 h with or without phorbol 12-myristate 13-acetate (PMA) stimulation. At each time point these cells were permeabilized and incubated with secondary conjugated FITC MoAbs specific for each cytokine. A flow cytometric system was developed to quantify specific intracellular fluorescence in T cells (CD3 þ ) and monocytes (CD14 þ ). TNF-a, IL-6 and IL-1b production in cell culture supernatants was also measured using ELISAs. In older subjects, flow cytometry detected significant increases in intracellular T cell TNF-a and IL-6 (P < 0·05). IL-1b was not detected in any of the T cell samples. Likewise, the monocytes of older subjects demonstrated increased intracellular levels of all three cytokines, but these increases were not significant (P > 0·05). These changes in intracellular proinflammatory cytokine levels may explain some of the exaggerated inflammatory responses seen in elderly patients.