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Makuuchi et al. J Cancer Metastasis Treat 2018;4:26  I  http://dx.doi.org/10.20517/2394-4722.2018.15                         Page 5 of 9

                                   Survival rate (%)
                                    100

                                    80


                                    60                             R0 (n = 17)

                                    40

                                                         R1 (n = 7)           P = 0.078
                                    20

                                     0
                                                 1                   2                    3                   4                    5
                                                             Survival time (years)

               Figure 1. OS curve of 24 patients. There were 17 patients who underwent R0 resection and 7 patients who underwent R1 resection. The
               5-year OS was better in patients who underwent R0 resection (38.8%) than in those who underwent R1 resection (0%), although the
               difference was not statistically significant (P = 0.078). OS: overall survival

               no difference in survival between these two patterns of invasion (P = 0.324). According to these studies,
               if R0 resection is considered possible, PD should be performed for patients with either primary tumor or
               metastatic lymph node invasion to the pancreatic head.


               Regarding the therapeutic benefit of PD for patients with tumors infiltrating the duodenum, no unified
               view has been obtained so far. Yonemura et al.  reported a survival benefit of PD over gastrectomy for T4b
                                                       [8]
                                                                      [10]
               tumors, but not for tumors with duodenal invasion. Ajisaka et al.  evaluated 69 gastric cancer patients with
               duodenal invasion; among them, 22 patients underwent PD and 47 patients underwent gastrectomy alone.
               When a negative resection margin was achieved (i.e., R0 resection), the 5-year survival rates were almost
               the same (37.3% for PD vs. 33.8% for gastrectomy alone), although patients who underwent PD had more
               frequent adjacent tissue infiltration and significantly longer extent of duodenal invasion. They also found
               that survival was worse when duodenal invasion was from lymph node metastasis than from the primary
               tumor. Therefore, they concluded that curative PD for gastric cancer improved the survival of patients with
               duodenal invasion, except when duodenal invasion was of the nodal type.

               Two studies have investigated the survival benefit of PD for patients with extensive lymph node metastases.
                             [8]
               Yonemura et al.  reported that PD improved the 5-year survival rate of patients with N3 lymph node
               metastasis (33% vs. 17%, P < 0.05). They used the first English edition of the Japanese Classification of Gastric
                         [21]
               Carcinoma , in which there were five N stages, with N3 referring to metastases in the hepatoduodenal, pre-
               and retropancreatic, and superior mesenteric nodes. In contrast, Hirose et al.  demonstrated that compared
                                                                                [9]
               with palliative gastrectomy, PD had a tendency to not improve MST for patients with N3 lymph node
               metastases (19 months vs. 20 months, the differences were not significant). Therefore, it is difficult to reach a
               conclusion from these opposing results.


               The other reported factors associated with better survival in patients who underwent PD included well-
                                        [15]
               differentiated histologic type , adjuvant intravenous chemotherapy , and metastatic lymph nodes less
                                                                          [17]
                        [14]
               than seven . Based on our experience of patients who underwent PD for gastric cancer, the 5-year overall
               survival (OS) rate was 27.5% and the MST was 17.2 months. The 5-year OS rate was 38.8% in patients
               who underwent R0 resection (n = 17) and 0% in those who underwent R1 resection (n = 7), although this
               difference was not statistically significant (P = 0.078), possibly due to the small sample size [Figure 1].
               The OS curves of patients who underwent R0 resection are shown in Figure 2. The 5-year survival rate
               was significantly higher in patients with predominantly pancreatic invasion than in those with duodenal
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