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Page 2 of 9                          Makuuchi et al. J Cancer Metastasis Treat 2018;4:26  I  http://dx.doi.org/10.20517/2394-4722.2018.15

               The pancreas is the organ most frequently invaded by gastric cancer [3-6] . When a tumor and/or
               lymphadenopathy invades the pancreatic head or infiltrates the duodenum, pancreaticoduodenectomy
               (PD) is the only possible treatment for achieving R0 resection. However, PD is a highly invasive procedure
               that cannot be performed on all patients. Since the first reported case of a patient who underwent PD for
                                  [7]
               gastric cancer in 1978 , all case series published [8-17]  were retrospective and single-center studies and no
               prospective study has been done. Because of the limited number of patients and heterogeneous data of the
               studies, definite indications for PD have not been established. Here we reviewed the literature on PD for
               gastric cancer and our own experience to clarify short- and long-term outcomes and the role of PD in gastric
               cancer.


               METHODS OF LITERATURE SEARCH
               We conducted a literature search on PubMed using keywords “gastric cancer”, “pancreaticoduodenectomy”,
               and “multivisceral resection” considering articles published until November 2017. We excluded inaccessible
               abstracts or articles not written in English. In addition, we reviewed patients who underwent distal or
               total gastrectomy with PD at Shizuoka Cancer Center (Shizuoka, Japan) between September 2002 and
               December 2015. We collected patients’ characteristics and pathological and surgical findings from our
               database and individual patients’ electronic medical records. In addition, we statistically analyzed our data
               using R Statistics version 3.4.0 (R Foundation for Statistical Computing, Vienna, Austria). Furthermore, we
               calculated 5-year survival rates using the Kaplan-Meier method and compared them between the groups
               using the log-rank test. The statistical significance of data was defined as P < 0.05.


               SHORT-TERM SURGICAL OUTCOMES
                                                                                             [7]
               PD is a highly invasive procedure that requires high surgical skills. When Buchholtz et al.  first reported
               PD for gastric cancer in 1978, they concluded that this treatment should not be performed because of the
               unacceptable risk without an additional and greater degree of palliation or likelihood of cure; however, they
               did not discuss their reasons in detail. Several studies have demonstrated short-term surgical outcomes of
               PD, including intraoperative blood loss, operation time, morbidity, and mortality [Table 1] [8-17] . The median
               amount of blood loss was reported to be > 1000 mL and the median operation time was as long as 7 h.


               Although several studies have concluded that PD for gastric cancer is feasible in terms of safety, the
               incidence of postoperative complications ranged widely from 22% to 74%, probably because of discrepancies
               in the definitions of complication. No study defined the exact criteria for postoperative complications
               because many of these reports were published before the definitive criteria for postoperative complications,
                                           [18]
               the Clavien–Dindo classification , were established. The mortality rate of PD was reported to be from 0%
               to 13%; however, the definition of the period of operative death differed among the studies; some defined
               mortality as death from any cause within 30 days after surgery, whereas the others did not mention the
                                              [14]
               period. The study by Nunobe et al. , who defined mortality as death from any cause before discharge,
               reported the highest mortality of 13%.
                                [16]
               Although Min et al.  reported the lowest complication rate of 22% among the reported rates of the previous
               studies, they also demonstrated one of the highest mortality rates, which was 11%. These results meant that
               half of the patients who suffered from postoperative complications died; this 50% mortality rate among
               patients who suffered postoperative morbidity seemed to be a bit high, which was possibly due to the
                                                                                 [8]
               variable definitions of all the complications. At the same time, Yonemura et al.  reported a 23% incidence of
               pancreatic fistula, but did not report the incidence of all complications.

                        [11]
               Saka et al.  reported the highest complication rate of 74%, with pancreatic fistula being the most frequent in
               44% of patients; all patients recovered with conservative management and none reported operation-related
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