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Page 4 of 12 Kamiya et al. J Cancer Metastasis Treat 2018;4:35 I http://dx.doi.org/10.20517/2394-4722.2017.76

Lymph node dissection
Lymph node dissection is an important part of achieving local tumor control in gastric cancer treatment,
and there has been much debate over the years on the optimal extent of this dissection. Traditionally, D2
lymph node dissection has been performed in Japan as standard practice since the 1960s, on the basis of
[13]
excellent long-term outcomes in Japanese case series . In Japan, D2 is the norm, while many surgeons in
the West still prefer to perform D1 dissection. One of the reasons is the results of the well-known Dutch
[33]
randomized clinical trial , which compared the survival advantage of D2 lymph node dissection with D1
resection, failing to demonstrate any benefits in D2 group in the main overall survival analysis. However, in
this trial the postoperative mortality was very high in the D2 arm, which counterweighed any potential sur-
vival advantage of the extended lymph node dissection at 5 years follow-up. A stratified analysis showed that
a large proportion of the morbidity and mortality in the D2 group was related to synchronous splenectomy
and pancreatectomy while in the subgroup of patients without pancreaticosplenectomy the risk of relapse
was significantly lower in the D2 compared to D1 group. However, in 10-year follow-up there was a signifi-
[34]
cant advantage in overall survival for the D2 group , despite the great losses in the early postoperative pe-
[35]
riod. This and other publications showing excellent short term outcomes after D2 gastrectomy in Western
high volume centres has led to the current Western consensus that D2 dissection should be the standard
[5]
procedure if carried out in specialized, high-volume centers .
Laparoscopic gastrectomy
Laparoscopic gastrectomy was launched in 1991 and the first laparoscopic total gastrectomy with D2 lymph-
adenectomy for advanced gastric cancer was reported in 2000 in Japan [36,37] . The clinical objective with this
technique was to minimize the surgical access trauma while still providing the same oncological operation,
in terms of T- and N-radicality, as open gastrectomy. Advantages suggested and to some extent proven with
laparoscopic gastrectomy, compared to open surgery, are less postoperative pain, earlier recovery of bowel
function, shorter hospital stay and better cosmetic result [37-39] . Furthermore, the concern from sceptics re-
garding the efficacy of the laparoscopic lymphadenectomy, has been relieved, as the number of harvested
[40]
lymph nodes has been shown to be comparable to that of open surgery . Although laparoscopic distal gas-
trectomy for early gastric cancer is gradually accepted as an oncologically safe alternative to open gastrec-
tomy in Europe, laparoscopic total gastrectomy and laparoscopic D2 lymph node dissection for advanced
cases are still considered challenging, due to their technical nature. With respect to surgical and oncological
safety, these procedures should be carefully implemented in experienced hands at centres with high annual
caseloads.

ADJUNCT THERAPY
Many clinical phase III trials on adjunct therapy for gastric cancer have been conducted worldwide. Despite
high-level evidence supporting the principle of adjuvant or neoadjuvant treatment, there is no standard of
care for adjunct treatment in gastric cancer. Main landmark trials are summarized in Table 2. The two major
[41]
studies of adjunctive therapy in western populations, the North American Intergroup INT0116 trial , the
[42]
MAGIC trial , demonstrated two major directions, postoperative chemoradiotherapy (CRT) and periop-
[43]
erative CT. Through many clinical trials, new regimens such as FLOT , enhancement of preoperative treat-
ment, and application of molecular targeted therapeutics are attracting much attention.

Postoperative chemotherapy and chemoradiotherapy
[41]
The INT0116 trial, the first randomized study evaluating the benefit of adjuvant CRT , and a subsequent
retrospective Dutch trial demonstrated that postoperative CRT improved OS and reduced local recurrence
[34]
rates following D1 lymph node dissection or R1 resection . Also the additional survival benefit of adjuvant
[44]
[45]
CT has shown by Asian phase III ACTS-GC and CLASSIC trial in Asian patients. However, the ART-
[46]
IST trial , a phase III trial from Korea, and the recent Dutch CRITICS trial failed to show a survival advan-
tage of postoperative additional radiation therapy to perioperative CT [47,48] . In the CRITICS trial, only 47%