Defining a positive circumferential resection margin in oesophageal cancer and its implications for adjuvant treatment.

BACKGROUND: A positive circumferential resection margin (CRM) has been associated with a poorer prognosis in oesophageal and oesophagogastric junctional (OGJ) cancer. The College of American Pathologists defines the CRM as positive if tumour cells are present at the margin, whereas the Royal College of Pathologists also include tumour cells within 1 mm of this margin. The relevance of these differences is not clear and no study has investigated the impact of adjuvant therapy. The aim was to identify the optimal definition of an involved CRM in patients undergoing resection for oesophageal or OGJ cancer, and to determine whether adjuvant radiotherapy improved survival in patients with an involved CRM. METHODS: This was a single-centre retrospective study of patients who had undergone attempted curative resection for a pathological T3 oesophageal or OGJ cancer. Clinicopathological variables and distance from the tumour to the CRM, measured to ± 0.1 mm, were correlated with survival. RESULTS: A total of 226 patients were included. Sex (P = 0·018), tumour differentiation (P = 0·019), lymph node status (P < 0·001), number of positive nodes (P < 0·001), and CRM distance (P = 0·042) were independently predictive of prognosis. No significant survival difference was observed between positive CRM 0-mm and 0·1-0·9-mm groups after controlling for other prognostic variables. Both groups had poorer survival than matched patients with a CRM at least 1 mm clear of tumour cells. Among patients with a positive CRM of less than 1 mm, those undergoing observation alone had a median survival of 18·6 months, whereas survival was a median of 10 months longer in patients undergoing adjuvant radiotherapy, but otherwise matched for prognostic variables (P = 0·009). CONCLUSION: A positive CRM of 1 mm or less should be regarded as involved. Adjuvant radiotherapy confers a significant survival benefit in selected patients with an involved CRM.

Glutathione supplementation to University of Wisconsin solution causes endothelial dysfunction.

INTRODUCTION: Glutathione (GSH) is added to University of Wisconsin (UW) organ preservation solution to protect against oxidative stress. This study assesses the effect of GSH-supplementation on endothelial function in tissues subjected to cold ischaemia and compares its effects to a mono-ethyl ester equivalent (GSH-MEE) and S-nitrosated GSH (GSNO). METHODS: Rat aortic rings were stored for 1 h or 48 h in cold, hypoxic UW solution with or without GSH (3 mM), GSH-MEE (3 mM) or GSNO (100 mciroM) supplementation. Aortic rings were reoxygenated in warm Krebs solution; smooth muscle function was assessed by responses to phenylephrine (PE), and endothelial function by vasodilatation to the endothelium-dependent dilator, acetylcholine (ACh). The protective effects against oxidant-induced endothelial cell death were assessed in cultured human umbilical vein endothelial cells (HUVEC). RESULTS: Supplementation of UW with either GSH or GSH-MEE had no effect on vascular responses to PE, but smooth muscle contraction was significantly attenuated in rings incubated for 48 h with GSNO. Endothelium-dependent relaxation was significantly impaired in tissues stored under hypoxic conditions in GSH, GSH-MEE and GSNO supplemented UW solution for 1 h. However, impairment at 48 h was significantly more pronounced in GSH-treated vessels. Cultured HUVEC death was exacerbated by GSH and GSH-MEE in unstressed cells and in those stressed with a superoxide anion generator. CONCLUSIONS: GSH supplementation of UW solution exacerbates cold-ischaemia induced endothelial dysfunction. GSNO did not share the detrimental effects of GSH and promoted NO-mediated vasodilatation.

Stability of ascorbic acid in orange juice exposed to light and air during storage.

Single-strength orange juice prepared from three nationally available brands of frozen orange juice concentrate was analyzed for ascorbic acid after exposure to light and air for varying periods up to eighteen days. For two of the brands, brown, foil-covered bottles offered no greater protection against ascorbic acid loss than clear glass bottles. Storage time appeared to be a greater contributor to ascorbic acid loss than type of container in two brands. One brand showed both the effect of storage time and type of container, since the juice stored in the brown bottle lost significantly less ascorbic acid after the same period than juice stored in the clear bottle.