Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Union Internacional Contra la Cancrum/American Joint Committee on Cancer.

BACKGROUND: In the surgical management of gastric carcinoma, regional lymphatic spread is of prognostic importance. The fifth edition of the Union Internacional Contra la Cancrum classification has been shown to be reproducible, practical and of significant prognostic use. The tumour node metastasis (TNM) system requires at least 15 lymph nodes to be acquired and examined for staging to be accurate. This has raised concern over the consistency with which the requisite numbers of nodes would be acquired. This study was performed to assess how consistently surgically managed cases of gastric cancer in the West Midlands fulfilled this requirement to allow accurate staging. METHODS: Data from the West Midlands Cancer Intelligence Unit on all cases of gastric cancer registered from 1998 to 1999 were obtained and the number of lymph nodes documented for each surgically managed case was assessed. RESULTS: Overall, only 31.0 per cent of surgically resected cases could be assessed accurately according to the TNM system. The proportion staged accurately varied widely across hospitals from 10.9 to 76.0 per cent. CONCLUSION: These results reflect the need for improved N staging across the region to aid the appropriate multimodal treatment of patients.

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial.

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.

The long term results of endoscopic surveillance of premalignant gastric lesions.

BACKGROUND: A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. AIMS: This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. PATIENTS: A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. METHODS: Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. RESULTS: Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. CONCLUSIONS: In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.

Redefining surgery for gastric cancer.

BACKGROUND: Despite encouraging retrospective and non-randomized trials, two large prospective, randomized trials of D1 vs D2 resections show double the mortality in the D2 group, with no increase in long-term survival. However, the D2 resection still offers the only hope of cure when N2 nodes are involved. We propose a reclassification of the International Union Against Cancer TNM "N" staging to a system with an anatomical basis that is useful in defining the surgery performed. Junctional nodes lying between the N1 and N2 tiers will act as a guide to surgery. Where these nodes are uninvolved, the probability of gastric bed (N2) involvement is low and the radical D2 dissection with its higher mortality and morbidity can be avoided.CONCLUSION: Such "stage-appropriate" surgery will reduce the number of D2 resections while ensuring that patients with N2 disease are not denied curative surgery. A prospective, randomized, controlled trial of targeted surgery is required.