• Clinical impact of tumour involvement of the anastomotic doughnut in oesophagogastric cancer surgery.

      Sillah, Abdul Karim; Griffiths, Ewen A; Pritchard, S A; Swindell, Ric; West, Catharine M L; Page, Richard; Welch, I M; Department of Gastrointestinal Surgery, University Hospital of South Manchester NHS Foundation Trust, UK. (2009-04)
      INTRODUCTION: Published colorectal cancer surgery data suggest no role for the analysis of the anastomotic doughnuts following anterior resection. The usefulness of routine histological analysis of the upper gastrointestinal doughnut is not clear. Our study assessed the impact of cancer involvement of the doughnut on clinical practice. Factors associated with doughnut involvement and the effect on patients' survival were also analysed. PATIENTS AND METHODS: The clinicopathological details of 462 patients who underwent potentially curative oesophagogastrectomy for cancer with a stapled anastomosis between 1994 and 2006 in two specialist centres were retrospectively analysed. Univariate, multivariate and survival analyses were carried out. RESULTS: Approximately 5% of doughnuts (22 of 462) were histologically involved with cancer. Microscopic involvement of the proximal resection margin, local lymph node metastasis and lymphatic invasion within the main resected specimen were independently associated with doughnut involvement (all P < 0.05). However, these three factors taken together failed to predict doughnut involvement. Doughnut involvement was an independent adverse prognostic factor for overall survival (P = 0.0013). CONCLUSIONS: In contrast to findings in colorectal surgery, doughnut involvement with cancer appears to have useful prognostic information following oesophagogastrectomy. Routine histological analysis of upper gastrointestinal doughnuts is justified. Doughnut involvement could potentially strengthen the indications for adjuvant therapy in the future.
    • Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis.

      Griffiths, Ewen A; Pritchard, S A; McGrath, S M; Valentine, Helen R; Price, Patricia M; Welch, I M; West, Catharine M L; Academic Department of Radiation Oncology, School of Cancer & Imaging Sciences, The University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK. (2008-03-11)
      The study investigated hypoxia-associated markers (HIF-2alpha, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2alpha in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n=20), Helicobacter pylori-associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. Relationships between HIF-2alpha expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2alpha was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2alpha-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2alpha-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2alpha had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2alpha has no role as a routine prognostic indicator. However, the high expression of HIF-2alpha suggests that it may be of value as a potential therapeutic target.