Maurizio Degiuli

BACKGROUND: It is still unclear whether D2 lymphadenectomy improves the survival of patients with gastric cancer and should therefore be performed routinely or selectively. The aim of this multicentre randomized trial was to compare D2 and D1 lymphadenectomy in the treatment of gastric cancer. METHODS: Between June 1998 and December 2006, patients with gastric adenocarcinoma were assigned randomly to either D1 or D2 gastrectomy. Intraoperative randomization was implemented centrally by telephone. Primary outcome was overall survival; secondary endpoints were disease-specific survival, morbidity and postoperative mortality. RESULTS: A total of 267 eligible patients were allocated to either D1 (133 patients) or D2 (134) resection. Morbidity (12.0 versus 17.9 per cent respectively; P = 0.183) and operative mortality (3.0 versus 2.2 per cent; P = 0.725) rates did not differ significantly between the groups. Median follow-up was 8.8 (range 4.5-13.1) years for surviving patients and 2.4 (0.2-11.9) years for those who died, and was not different in the two treatment arms. There was no difference in the overall 5-year survival rate (66.5 versus 64.2 per cent for D1 and D2 lymphadenectomy respectively; P = 0.695). Subgroup analyses showed a 5-year disease-specific survival benefit for patients with pathological tumour (pT) 1 disease in the D1 group (98 per cent versus 83 per cent for the D2 group; P = 0.015), and for patients with pT2-4 status and positive lymph nodes in the D2 group (59 per cent versus 38 per cent for the D1 group; P = 0.055). CONCLUSION: No difference was found in overall 5-year survival between D1 and D2 resection. Subgroup analyses suggest that D2 lymphadenectomy may be a better choice in patients with advanced disease and lymph node metastases. REGISTRATION NUMBER: ISRCTN11154654 (http://www.controlled-trials.com).

BACKGROUND: A randomized clinical trial was performed to compare D1 and D2 gastrectomy in specialized Western centres. This paper reports short-term results. METHOD: A total of 267 patients with gastric cancer were randomly assigned to either a D1 or a D2 procedure in five specialized centres. Based on the findings of the phase II trial and published phase III trials, a prespecified non-inferiority boundary at 12 per cent difference between groups was set regarding total morbidity. RESULTS: In the intention-to-treat analysis, the overall morbidity rate after D2 and D1 dissections was 17.9 and 12.0 per cent respectively (P = 0.178), with a 95 per cent confidence interval of the difference of 0 to 13.0 per cent, slightly exceeding the prespecified non-inferiority limit. There was a single duodenal stump leak in the D2 arm (0.7 per cent). The postoperative 30-day mortality rate was 3.0 per cent after D1 and 2.2 per cent after D2 gastrectomy (P = 0.722). CONCLUSION: In specialized centres the rate of complications following D2 dissection is much lower than in published randomized Western trials. D2 dissection, in an appropriate setting, can therefore be considered a safe option for the radical management of gastric cancer in Western patients. REGISTRATION NUMBER: ISRCTN11154654 (http://www.controlled-trials.com).

Curative resection is the treatment of choice for potentially curable gastric cancer. Two major Western studies in the 1990s failed to show a benefit from D2 dissection. They showed extremely high postoperative mortality after D2 dissection, and were criticised for the potential inadequacy of the pretrial training in the new technique of D2 dissection, prior to the phase III studies being initiated. The inclusion of pancreatectomy and splenectomy in D2 dissection was associated with increased morbidity and mortality. Following these results, we started a phase II trial to evaluate the safety and efficacy of pancreas-preserving D2 dissection. The results of this trial regarding the safety of pancreas preserving D2 dissection were published in 1998. In this paper, we present the survival results of this phase II trial to confirm the rationale of carrying out a phase III study comparing D1 vs D2 dissection for curable gastric cancer. Italian patients with histologically proven gastric adenocarcinoma were registered in the Italian Gastric Cancer Study Group Multicenter trial. The study was carried out based on the General Rules of the Japanese Research Society for Gastric Cancer. A strict quality control system was achieved by a supervising surgeon of the reference centre who had stayed at the National Cancer Center Hospital, Tokyo, to learn the standard D2 gastrectomy and the postoperative management. The standard procedure entailed removal of the first and second tier lymph nodes. During total gastrectomy, the pancreas was preserved according to the Maruyama technique. Complete follow-up was available to death or 5 years in 100% of patients and the median follow-up time was 4.38 years. Out of 297 consecutive patients registered, 191 patients were enrolled in the study between May 1994 and December 1996. The overall morbidity rate was 20.9%. The postoperative in-hospital mortality was 3.1%. The overall 5-year survival rate among all eligible patients was 55%. Survival was strictly related to stage, depth of wall invasion, lymph node involvement and type of gastrectomy (distal vs total). Our results suggest a survival benefit for pancreas-preserving D2 dissection in Italian patients with gastric cancer if performed in experienced centres. A phase III trial among exclusively experienced centres is urgently needed.