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Ida et al. J Cancer Metastasis Treat 2018;4:22  I  http://dx.doi.org/10.20517/2394-4722.2017.75                                    Page 3 of 9

               all patients was 29.8 months, although these premature data were calculated after a median follow-up time
               of only 12.4 months. However, only D2 lymph node dissection was performed in that study; the fact that
               PAND was not performed should be considered . The authors’ strategy was to convert chemotherapy to
                                                         [7]
               surgical therapy for selected responders in the hope that up to six cycles of chemotherapy might cure the
               cancers outside the confines of standard surgical dissection. In contrast, the Japanese investigators treated
               patients by neoadjuvant chemotherapy to eliminate micrometastases that may or may not have been present,
               followed by surgery with curative intent to dissect all cancerous tissues that had been detected prior to the
               treatment. Therefore, the philosophy behind the two strategies is quite different.

               Whether the preoperative diagnosis of para-aortic lymph node metastasis is reliable must be considered when
               discussing these treatment options. Lymph node metastasis is currently diagnosed when the lymph node
               diameter shows either a minor axis of ≥ 8 mm or major axis of ≥ 10 mm on abdominal computed tomography
               (CT). The JCOG 1302A trial, which evaluated the accuracy of clinical diagnosis and pathological stage III
               gastric cancer, showed that the sensitivity and specificity of the CT criteria for nodal metastasis were 62.5%
                                                   [8]
               (505/808) and 65.7% (278/423), respectively . A recent prospective study indicated that multidetector-row CT
               achieved relatively high overall accuracy (76%) in preoperative detection of nodal metastasis . Furthermore,
                                                                                            [9]
               Marrelli et al.  reported that the sensitivity and specificity of multidetector-row CT in detecting para-aortic
                           [10]
               lymph node metastasis were encouragingly high at 85% and 95%, respectively. Improvements in diagnostic
               accuracy also contribute to improvements in diagnostic modality.

               Liver metastases
               Colorectal liver metastases are widely considered targets of surgery with curative intent because they often
               present as liver-only diseases, and R0 resection showed favorable survival in a recent clinical study .
                                                                                                        [11]
               However, the necessity of surgical resection of liver metastases of gastric cancer is still controversial.

               The guidelines do not recommend surgery for stage IV gastric cancer; therefore, most patients with liver
               metastases of gastric cancer receive systemic therapy . In contrast, several studies have shown that long-term
                                                           [1]
               survival can be obtained by performing hepatectomy for liver metastases of gastric cancer. However, only
               retrospective analyses of small cohorts collected over several decades have been performed, and most were
               single-institution studies. No prospective trial exploring the benefits of hepatectomy has been conducted.


               We reviewed the 7 largest studies reported from 2012 to 2017, each with ≥ 50 patients who underwent
               hepatectomy for liver metastases from gastric cancer [12-17]  [Table 1]. In these series, the 3- and 5-year OS
               rates were 14.0% to 51.4% and 9.3% to 42.3%, respectively, with a median survival time (MST) of 13.0 to
               40.8 months [12-18] . Solitary metastasis or a small number of metastatic nodules was highlighted as a favorable
               prognosis in most of the studies. After multivariate analysis, Oki et al.  reported that more than two liver
                                                                           [16]
               metastases [hazard ratio (HR), 2.14; 95% confidence interval (CI), 1.16-3.97] and Kinoshita et al.  reported
                                                                                                [13]
               that three or more liver metastases are independent factors that is associated with worse prognosis (HR,
               2.33; 95% CI, 1.62-3.36). Oki et al.  also reported that the presence of three or more lymph node metastases
                                           [16]
               was a factor that is associated with worse prognosis. Moreover, a size of ≥ 3 cm  or ≥ 5 cm [12,13]  or serosal
                                                                                   [15]
               invasion [12,13,18]  have been reported as an independent risk factors for the primary gastric cancer itself.
               However, these reports were the results of accumulation of cases over a long period of 10 to 20 years. Therefore,
               with the given the recent advances in imaging studies, it is possible that the diagnosis of the number of liver
               metastasis might not be reliable. Thus, hepatectomy may be considered for patients with a small number
               of metastatic nodules and not restricted to a solitary tumor, provided that no other noncurative factor is
               present. At present, it may be reasonable to keep the indication for hepatectomy when a patient has three or
               fewer metastases.
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