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Page 4 of 9                                     Ida et al. J Cancer Metastasis Treat 2018;4:22  I  http://dx.doi.org/10.20517/2394-4722.2017.75

               Table 1. Literature overview of outcomes following hepatectomy for gastric cancer liver metastases
                Ref.              Year    Country     Study      No. of    3-year OS   5-year OS   MST
                                                      interval   patients                        (months)
                Takemura et al. [12]   2012   Japan   1993-2011    64        50.0       37.0       34.0
                          [13]
                Kinoshita et al.    2015   Japan     1990-2010     256       41.9       31.1       31.1
                Tiberio et al. [14]    2015   Italy   1997-2011    53        14.0       9.3        13.0
                Oki et al. [16]    2016   Japan      2000-2010     94        51.4       42.3       40.8
                Tiberio et al. [18]    2016   Italy   1990-2013    105       20.3       13.1       14.6
                       [15]
                Guner et al.      2016    South Korea   1998-2013   68       40.6       30.0       24.0
                       [17]
                Song et al.       2017    China      2001-2012     96        47.6       21.7       34.0
               OS: overall survival; MST: median survival time
               Although chemotherapy has been successful and surgical cases are increasing, there is no evidence for the
               recommended chemotherapy regimen in this particular situation. Therefore, systemic chemotherapy is
               performed with reference to the treatment recommended by the guidelines . However, Tiberio et al.  reported
                                                                                                [18]
                                                                            [1]
               that adjuvant chemotherapy was a prognostic factor. Therefore, adjuvant chemotherapy after hepatectomy
               will be discussed as increasingly more cases are accumulated.

               Peritoneal dissemination
               The peritoneum is a frequent site for metastases in patients with advanced gastric cancer, and peritoneal
               dissemination is one of the most important life-threatening factors in such patients. Systemic chemotherapy
               is administered to patients with peritoneal dissemination as well as other patients with stage IV gastric
               cancer. Systemic chemotherapy for gastric cancer has steadily progressed in recent years, and 5-fluorouracil-
               based or cisplatin-based regimens are generally accepted as possible standard chemotherapy. However, an
               adequate therapeutic effect has not been obtained. Otherwise, the treatment strategy for patients with only
               positive peritoneal cytology remains controversial. The Japanese Gastric Cancer Association advocates
               classification of free cancer cells in the peritoneal cavityas M1, and surgery with curative intentis not
               indicated according to the treatment algorithm of the current guidelines. However, the guidelines suggest
               that a cytology-positive status in the absence of other noncurative factors (i.e., macroscopic disease) can be
               managed with D2 gastrectomy and perioperative chemotherapy .
                                                                     [1]
               Intraperitoneal  (i.p.) chemotherapy  has recently been  conducted to  improve  the treatment outcomes for
               peritoneal dissemination. Ishigami et al.  developed a regimen involving the addition of weekly i.p. paclitaxel
                                                [19]
               (PTX) to an established systemic chemotherapy regimen of S-1 and intravenous PTX for the treatment of
               peritoneal metastasis of gastric cancer. The i.p. PTX was administered to enhance antitumor activity against
               peritoneal metastasis by maintaining a high concentration of the drug in the peritoneal cavity over a long
               period, and its clinical effects have been verified by several convincing clinical trials involving patients with
               ovarian cancer with peritoneal metastasis . In a phase II trial conducted by Ishigami et al. , 40 patients with
                                                  [20]
                                                                                          [21]
               gastric cancer that was positive for peritoneal metastases and/or peritoneal cytology were enrolled. The authors
               reported a 1-year OS rate of 78%. In addition, malignant ascites disappeared or decreased in 13 of 21 (62%)
               patients, and cancer cells detected by peritoneal cytology diminished in 24 of 28 (86%) patients. In a phase
               III trial comparing this i.p. chemotherapy to S-1 plus cisplatin (PHOENIX-GC trial), the primary analysis
               did not show the statistical superiority of the i.p. regimen (P = 0.08; HR, 0.72; 95% CI, 0.49-1.04), however,
               prolongation of the MST by 2.5 months was recognized in the i.p. group, and the i.p. chemotherapy could
               thus be considered a promising treatment option . Furthermore, Ishigami et al.  performed a retrospective
                                                                                  [23]
                                                        [22]
               study of 100 cases of P1 and/or CY1 gastric cancer and found that conversion surgery was performed in 64
               patients, among whom R0 resection was performed in 44 (69%).

               Table 2 shows the promising results of several phase II clinical trials of i.p. taxanes after 2010. In these series,
               the 1-year OS rates were 69% to 78%, with an MST of 16.2 to 24.6 months [21,24-27] . Notably, the possibility of
               negative peritoneal cytology was very high at 81.8% to 97.0%.
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