Abad et al Table 1 Deﬁnition of “R” and “D”. R refers to the type of resection carried out. D refers to the extent of the lymph node dissection R0 R1 R2 D1 D2 Curative resection without residual disease Resection with curative intention but with microscopic residual disease Palliative resection with macroscopic residual disease Resection of tumor and adjacent nodes only Resection including coeliac and perigastric nodes up to >3 cm of the primary T aspect. The study by the German group (German Gastric Cancer Study group) Roder et al 1993 (record study) showed that patients in stages II and IIIA who had undergone R0 and D2 surgery (>25 nodes resected) gained signiﬁcant im- provement in survival compared with those patients who had undergone standard resection. The Dutch study (Bonenkamp et al 1999) (randomized study) and the Cuschieri study (Cus- chieri et al 1999) reached the opposite conclusion – that D2 surgery should not be considered as the standard treatment. In this study, the extent of the surgery (D1 vs. D2) entailed better staging of patients, without showing improvement in survival for the stages. However, it is difﬁcult to ignore that in the German study, the survival at 5 years increased from 26% to 55% in stage II for D2 surgery. In this context, the role of adjuvant chemotherapy has not been deﬁned. There are other relatively recent studies with signiﬁcant results, although the majority of these could not be reproduced, or lack statistical power due to the small number of cases (Table 4). The studies by Cirera et al (1999) and Neri et al (2001) are worth a separate mention. In the study by Neri et al the treatment used was epirubicin, 5-ﬂuorouracil (5-FU) and leucovorin (LV). We can include this as a more common treatment than those used in most studies that make up the meta-analyses published until now. All patients had positive nodes; 88% of patients received the scheduled treatment. The average survival for the group treated was 31 months, almost double that of the control group, which had an aver- age survival of 18 months (p < 0.01). The survival at 5 years Table 2 Survival at 5 years by stage and location of tumor Stage Overall Antrum/pylorus Cardia/fundus IA 78% 81% 64% IB 58% 65% 42% II 34% 38% 24% IIIA 20% 23% 13% IIIB 8% 6% 6% IV 7% 9% 6% 564 Table 3 Distribution of gastric cancer relapses Local Peritoneal Distant Ref. 23% 54% 54% Schwarz et al 2002 42%–48% 21%–52% 25%–46% Marrelli et al 2002 29% 72% 18% Macdonald et al 2001 38%–93% 30%–43% 49% Gunderson et al 2002 was 30% of treated patients in contrast with 13% of the control group. Although there was toxicity grade 3–4, with 12% of patients having mucositis, 8.7% diarrhoea and 7% leukopenia, the level of toxicity was acceptable and there were no cases of hospitalization. The study by Cirera et al involved 156 patients, all in stage III including cases of N0. In this study, the treatment was very simple and included a single dose of mitomycin (MMC) followed by 3 months of oral tegafur daily. It is important to highlight that all the patients included had undergone R0 D2 surgery. The results were highly signiﬁcant, with 56% survival at 5 years for the treated group and 31% for the control group (p = 0.04). In this case, the price of obtaining the survival beneﬁt was minimal, with only one case of grade 3 toxicity. Although conﬁrmation studies with a greater number of cases are necessary, these data should not be ignored. In the study by Cirera et al the greatest percentage of relapses were local and peritoneal, reaching 33% in the non-treated group. Although no signiﬁcant results were reached, the study developed by ITMO group (Italian Trials in Medical Oncology) is very interesting. There were 274 patients included in it with T3, T4 or N1, N2. Chemotherapy consisted of two cycles of EAP (etoposide, adriamycin, and cisplatin) followed by two cycles of 5FULV according to Machover’s scheme with leucovorin. Survival at 5 years was 48% for the control group and 52% for the treatment group without signiﬁcant statistical differ- ence. The highest beneﬁt was for patients N+ with more than 6 nodules whose survival was 22% and 42% respectively. The authors also point out the importance of the D2 surgery performed in the study, inﬂuencing the high survival achieved in both groups (Bajetta et al 2002). Some molecular alterations have been described in gastric cancer as indicative factors of different biological behavior and prognosis which may relate to the different results achieved. We quote as an example the microsatellite instability, present in 13%–44% of sporadic gastric cancers which confers better prognosis (dos Santos et al 1996) or some speciﬁc somatic changes that can occur in p53 without a clear prognosis or in p16INK4 related to gastroesophageal junction cancers (Wong et al 1997). The anatomical location Therapeutics and Clinical Risk Management 2007:3(4)