TUGAS BAHASA INGGRIS

TEMU 2

A12-B
KELOMPOK 3

I GEDE GARGITA (18.321.2867)

NI KADEK AYU DEWI CAHYANI (18.321.2877)
NI KETUT VERAWATI NANDINI (18.321.2887)
NI LUH PUTU DITA PUSPITA SARI (18.321.2896)

PROGRAM STUDI KEPERAWATAN PROGRAM SARJANA

SEKOLAH TINGGI ILMU KESEHATAN
WIRA MEDIKA BALI
DENPASAR
2020
JJCO Japanese Journal of
Clinical Oncology
Japanese Journal of Clinical Oncology, 2016, 46(11) 1062–1071
doi: 10.1093/jjco/hyw117
Advance Access Publication Date: 30 August 2016
Special Lecture Note

Special Lecture Note

The current state of stomach cancer surgery

in the world

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Yasuhiro Kodera*
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

*For reprints and all correspondence: Yasuhiro Kodera, Department of Gastroenterological Surgery, Nagoya University
Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. E-mail: ykodera@med.
nagoya-u.ac.jp
Received 12 June 2016; Accepted 27 July 2016

Abstract
The incidence of gastric cancer and the number of gastric cancer patients that a surgeon treats annu-
ally are so vastly different between countries and regions that it is not easy to define which type of
gastric cancer surgery should be considered the global standard. Nevertheless, a consensus that D2
dissection is the most appropriate way to treat resectable advanced gastric cancer has arguably
been reached after long-term follow-up and flexible interpretation of the Dutch D1 versus D2 trial and
evidence from the Japan Clinical Oncology Group 9501 study which denied survival benefit of more
extensive lymphadenectomy. After the Japan Clinical Oncology Group 9501 trial, surgeons gradually
lost interest in attempting to improve survival through extended resection and instead began to
expend greater resources on establishing and standardizing the technique of minimally invasive sur-
gery and proving its oncological non-inferiority compared with the conventional approach.
Laparoscopic distal gastrectomy has become an option in daily clinical practice in the Far East, and
more demanding procedures such as laparoscopic total gastrectomy and laparoscopic surgery for
advanced gastric cancer are currently being explored in clinical trials from the viewpoint of both
safety and oncological feasibility. In addition, the high proportion of early-stage cancer in the Far
East prompted surgeons to develop limited surgery such as proximal gastrectomy and pylorus-
preserving gastrectomy, which warrant further evaluation regarding benefits in terms of post-
operative nutritional state and/or quality of life measurements to convince the rest of the world.

Key words: gastrectomy, lymph node dissection, laparoscopic surgery, limited surgery

Introduction large-scale clinical trials in surgery and oncology, and efficiency in

Although gastric cancer remains a major health problem in several
countries and regions, the incidence has been particularly high in the
Far East, including People’s Republic of China (China), Japan,
Korea and Taiwan (1). Surgery remains the only treatment modality
with potential to cure gastric cancer, although prognostic relevance
of multimodality strategy has been well-documented. Infrastructure
for screening, early diagnosis and surgical treatment was primarily
established in Japan, and was rapidly disseminated to other coun-
tries in the Far East. Currently, Korea has been the most successful
country in centralization of the patients so that several hospitals in
and around Seoul perform well over 1000 gastrectomies annually (2).
This situation prompted researchers in that country to organize
patient accrual was such that they have began to take central roles
in pivotal international clinical trials. China has become another ris-
ing force in generating evidences through clinical trials, although the
quality of care may not be as standardized throughout the country
as it is in Korea, given the extremely large population. In the mean
time, Taiwan has been the only country in the world that published
a positive data in a surgical randomized trial comparing extended
versus limited lymphadenectomy (3). In some other parts of the
world, and particularly in the USA and Western Europe, the inci-
dence of gastric cancer has declined and efforts for screening and
early detection has not been an issue of higher priority over manage-
ment of other diseases. Thus, gastric cancer in the West is often

© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 1062

found as more advanced disease and is either inoperable or in need
of more radical surgery for resection. This fundamental difference in
the background will have to be taken into consideration when dis-
cussing why the quality and diversity of surgical care for gastric cancer
had not been similar throughout the world.
Biology of gastric cancer and philosophy behind
lymph node dissection for early gastric cancer
Gastric cancer occurs due to genetic changes (Mutations ) in
stomach cells, which cause these cells to grow abnormally and out
of control. These cells are called cancer cells. Gastric cancer is a
disease with aggressive biology, and is known to eventually
disseminate simultaneously by several metastatic routes, creating a
mixed pattern of treatment failure that is considered char- acteristic
of the disease . (4). While detection of micrometastases and
isolated cancer cells in the bone marrow (5) or in the form of circu-
lating tumor cells (6) have been reported even in early-stage cancer,
clinical relevance of these cells along with whether they indeed are
representing viable cancer cells remain questionable, given the excel-
lent long-term survival of patients with early cancer who underwent
curative resection (7). According to a large case series, hematogen-
ous metastases are occasionally observed once cancer invades into
the proper muscle layer (8), and the incidence of peritoneal metasta-
ses through dissemination directly from the serosal surface rise
abruptly once cancer invades the serosa (9).
In contrast, cancer cells spread through the lymphatics even dur-
ing relatively early stages. In Japan, it has for a long time been cus-
tomary that surgeons who took part in surgery perform ex-vivo
lymph node retrieval (10). In other words, they scrutinize the
resected specimens after surgery and harvest lymph nodes from the
adipose tissues that were removed en bloc with the stomach. One
Figure 1. Lymph node stations in numbers as determined by the Japanese Classification of Gastric Carcinoma (11).
Jpn J Clin Oncol, 2016 , Vol. 46, No. 11 1063
bottle containing formalin is prepared for each lymph node station
as numbered by the Japanese Classification of Gastric Carcinoma
(Fig. 1) (11), and lymph nodes retrieved from one lymph node station
are dipped into the corresponding bottle, so that a surgeon will leave
behind up to around 20 bottles accompanied with a stomach
immersed in formalin after being opened and neatly pinned on a
board. Analysis of a vast number of surgically resected specimens
treated this way have shown that the incidence of nodal metastasis
increases incrementally as cancer invades deeper into the stomach
wall, and that the incidence of lymphatic metastasis approaches 20%
as the tumor invades into the submucosa (12). This denotes, in the-
ory, that lymphadenectomy is desirable even for early gastric cancer.
Through such database, it was also possible to define a criteria
whereby the risk of harboring nodal metastasis is virtually nil for
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cancers which satisfy that criteria (13); namely, differentiated type
cancer with a diameter of 2 cm or less without ulcerative findings.
These criteria have in turn been serving as the absolute criteria to
perform the endoscopic submucosal dissection (ESD) which, using
the natural orifice, is the least invasive type of surgery for gastric can-
cer (14). In addition, it was clear that lymph node metastasis from
early (T1-stage) cancer rarely spreads into the second tier lymph
nodes, encouraging surgeons to devise and evaluate various limited
gastrectomies often accompanied with limited D1 (dissection of peri-
gastric lymph nodes en bloc with the stomach) or D1+ (dissection of
suprapancreatic lymph nodes along the common hepatic artery and
around the celiac axis in addition to D1) lymph node dissection.
Prevalence of gastric cancer, lack of symptoms that facilitate diag-
nosis and extremely poor outcome of advanced/metastatic cancer
prompted the Japanese community to adopt screening programs and
to train physicians who are devoted to early diagnosis. Barium
1064 The current state of stomach cancer surgery in the world
swallow had long been the method for screening, and finding early-
stage cancers through the double contrast technique became some-
thing of a cult among the gastroenterologists and radiologists in the
latter-half of the twentieth century. As a typical example, late Dr
Masakazu Maruyama, a legendary gastroenterologist, wrote a text
book describing practical tips of the double contrast technique in
which he accused an anonymous fellow surgeon of extending the
stomach thoughtlessly when pinning it down on a board for pho-
tography followed by fixation in formalin, as a result of which a
subtle fold he had delineated beautifully in the radiograph had van-
ished from the photograph of the resected specimen. This meticu-
lousness and enthusiasm has been passed on to the endoscopists
who now struggle to find candidates for the ESD. Consequently,
well over 50% of gastric cancer diagnosed in Japan (7) and Korea
currently fall into Stage I, which is in stark contrast with the
situation in other countries.
As mentioned previously, Stage I gastric cancer that does not sat-
isfy the criteria for the ESD has a possibility, albeit remote, of har-
boring nodal metastases, and is therefore deemed eligible for
gastrectomy with D1, D1+ or D2 (more extensive dissection of
suprapancreatic lymph nodes along the hepatic and splenic artery
and around the celiac artery in addition to the perigastric lymph
nodes) lymphadenectomy according to the Japanese guidelines (14).
This overtly cautious attitude when treating early gastric cancer ori-
ginates from the time when finding an early cancer was a consider-
able challenge, made possible only by gastroenterology specialists
who were deeply dedicated to the early diagnosis. Task of a surgeon
at the time had been to avoid any unnecessary death due to subopti-
mal surgery and to raise and sustain the survival rate of patients
with early gastric cancer to as near 100% as possible to meet the
expectation of both the patients and those who detected the disease.
The high incidence of early gastric cancer that nevertheless was
indicated for the relatively complex surgery meant that, in compari-
son with other countries, surgeons in Japan and Korea were allowed
numerous opportunities to train themselves to perform lymphade-
nectomy by exposing major arteries and the pancreas without being
hindered by a bulky tumor, being held back by poor nutritional con-
dition of the patients, or feeling uncomfortable with a thought that
insufficient lymphadenectomy could easily lead to disease recurrence.
Lymphadenectomy for advanced resectable
gastric cancer
For more advanced cancer, the incidence of metastasis to each of the
nodal stations would increase, and more extensive nodal dissection
should be required. The Japanese surgeons adopted D2 dissection, a
systemic en bloc lymph node dissection to remove the second tier or
the suprapancreatic nodes, exposing the pancreas as well as major
vessels such as the common hepatic artery, proper hepatic artery,
splenic artery and the portal vein. Their philosophy was that all
lymph nodes that had the possibility of harboring metastasis should be
resected. Maruyama et al. created a computer program by which the
incidence of metastasis could be estimated for each lymph node station
once data regarding some preoperative predictors are entered (15).
However, an advanced disease may have developed into a systemic
disease and may harbor micrometastases to the distant organs in
which case the extended lymphadenectomy would become futile. To
avoid this problem, Sasako proposed a therapeutic index which can
be calculated through multiplying the incidence of metastasis to
each lymph node station by the observed 5-year survival rate of
patients with metastasis to that station (16). Lymph node stations
with low therapeutic indices could then be excluded from the list to
be resected, but most stations within the range of D2 dissection
were found to have sufficient therapeutic indices.
The long-term survival of the patients with curatively resected
gastric cancer had been different between the Western countries and
Japan where the D2 dissection had been the standard, even when
stage-by-stage comparisons were made (17). It was still unclear
whether this difference was due to the difference in tumor biology
between the regions, the stage migration (a phenomenon in which
more extensive lymphadenectomy leads to detection of a greater
number of nodal metastasis and pushes the patient into more
advanced stage, leading to improvement in stage-by-stage survival),
or the therapeutic effect of extended nodal dissection itself. To clar-
ify prognostic relevance of extended lymphadenectomy, several D2
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versus D1 randomized trials were conducted, of which the Dutch
and British trials had been the ones with sufficient statistical consid-
erations and sample size. However, these attempts failed to show
survival benefit of D2 dissection, at least partially because of high
operative mortality in the D2 arm reflected by the steep decline of
the survival curve for that arm early at the initial phase of the
follow-up (18,19). Eventually, the long-term follow-up of the Dutch
trial revealed significant increase in death due to gastric cancer
among the D1 group (20), suggesting that the D2 might have done
better had the surgery and postoperative care been conducted more
appropriately. The surgical mortality has now declined considerably
in the Netherlands and the UK due to surgical training and central-
ization of the patients to high-volume hospitals (21), and the princi-
pal investigator of the British trial declared that the results of their
trial are no longer sustainable arguments against D2 gastrectomy
today (22).
In the mean time, the Japanese investigators belonging to the
most prestigious study group of the surgeons and oncologists, the
Japan Clinical Oncology Group (JCOG), conducted JCOG9501, a
randomized comparison of D2 dissection with D2 plus para-aortic
lymph node dissection (PAND) (23). Only patients who were with-
out evidence of enlarged lymph nodes in the para-aortic regions
were eligible for inclusion. Long-term survivors had been reported
among patient with metastasis to the para-aortic nodes after PAND
in several Japanese retrospective case series (mostly published in
Japanese), and PAND had been widely performed by the Japanese
high-volume centers at the time. JCOG9501 became the first oppor-
tunity to show in a prospective trial setting quality of the Japanese
gastric surgery in terms of low mortality (0.8% for each arm), but
proved outright that there is no survival benefit in PAND which
took significantly longer operating time and resulted in greater
blood loss. The trial results at once brought the enthusiastic argu-
ments in Japan in support of the PAND to an end and D2 remained
the standard of care. The PAND is currently performed after neoad-
juvant chemotherapy only to treat patients with bulky lymph node
metastasis, including patients with a small number of enlarged nodes
in the para-aortic region, following favorable results from a series of
Phase II trials (24,25). It has also been conducted for selected
patients by the Italian surgeons (26), who claim some long-term sur-
vivors as did the Japanese surgeons before the JCOG9501 trial.
However, the interest of most of the surgeons has moved on from
the extended surgery to minimally invasive surgery.
Prognostic relevance of other components of the formal Japanese
D2 dissection such as splenectomy in case of cancer of the upper-
third stomach (JCOG0110) and bursectomy (JCOG1001) has more
recently been addressed by randomized Phase III trials. JCOG0110
has become the first prospective trial to prove statistically that total

gastrectomy without splenectomy is not inferior to total gastrectomy
with splenectomy (27), although the Western surgeons had already
discarded the idea of routinely performing splenectomy from their
experience with the D1 versus D2 Phase III trials (18,19).
The issue of surgical approach
Increase in the incidence of gastric cancer surgery by the laparo-
scopic or laparoscopy-assisted approach is shown in Fig. 2. The first
laparoscopic surgery for gastric cancer was a wedge resection by
Ohgami et al. (28). Assistance by endoscopy was often needed as a
guide to locate the tumor, to ensure sufficient resection margin and
to avoid excessive resection which may cause deformity and induce
stenosis of the stomach. In addition, oncological safety could not be
ensured once the tumor was outside the indication for the less inva-
sive endoscopic resection, because wedge resection does not permit
traditional systemic lymphadenectomy. The technique to locate and
excise the tumor in an ideal way developed further in the form of
Laparoscopic and Endoscopic Cooperative Surgery (29), and the
technique is currently in use for resection mainly of the gastrointes-
tinal stromal tumors. For cancer surgery in which exposure of the
gastric lumen to the peritoneal cavity is not desirable, further innov-
ation in the form of Non-exposed Endoscopic Wall-inversion
Surgery has been reported (30). Again, the need for lymphadenect-
omy confines its use for gastric cancer to exceptional situations
unless the sentinel node concept (31), now under reevaluation, could
be validated as a method to reliably identify the node-negative dis-
ease. On the other hand, the aging population and increase in the
proportion of elderly and frail gastric cancer patients could broaden
the applicability of these procedures. It may make sense to avoid
gastrectomy with systemic lymphadenectomy in elderly patients
with relatively low-risk of nodal metastases, especially when the dis-
ease is located in the upper-stomach.
all laparoscopic gastric cancer surgery
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
Figure 2. The annual number of laparoscopic gastric cancer surgery performed in Japan. The number increased exponentially as the laparoscopic gastrectomy
was approved by the Ministry of Health and Welfare in April 2006 (arrow). The data are derived from a questionnaire survey conducted by the Japan Society for
Endoscopic Surgery, in which the questionnaire was sent to 2412 institutions that includes members of the society and the res ponse retrieved from 1380
institutions.
Jpn J Clin Oncol, 2016 , Vol. 46, No. 11 1065
A distal gastrectomy with systemic lymphadenectomy was first
performed laparoscopically by Kitano et al. and reported in 1994 (32).
The technique was rapidly learnt and improved by a small number of
the ‘first-generation’ surgeons in Japan, and safety and feasibility of the
laparoscopic approach for early-stage cancer treated between 1994 and
2003 were eventually reported on the multi-institutional basis (33).
However, there were some cancer recurrences that were hard to explain
or accept during the early attempts by laparoscopic approach (34), and
patients did at the beginning suffer from higher morbidity than would
seem acceptable nowadays (35).
Nevertheless, the number of laparoscopic distal gastrectomy per-
formed in Japan increased exponentially after 2006, when the
Ministry of Health and Welfare approved the use of laparoscopic
approach for distal/total gastrectomy and to reimburse the cost of
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surgery plus some extra cost needed when this approach was
selected (Fig. 2). Although laparoscopic gastrectomy was usually
performed in selected patients with early gastric cancer, surgeon in
the Far East benefitted from sufficient number of opportunities to
train themselves with the laparoscopic approach thanks to the abun-
dance of clinically Stage I (cStage I) cancers, and to prepare for the
subsequent step of testing safety and oncological feasibility in more
advanced cancers (36,37).
JCOG decided after some reluctance that the laparoscopic
approach could be clinically too meaningful to be ignored as trivial
attempts and proceeded to evaluate the new approach. Some pre-
parations such as inclusion of prominent laparoscopic surgeons as
new members in the study group and qualification of new gener-
ation of laparoscopic surgeons to participate in the trial (38,39)
were necessary before JCOG could launch a Phase II study,
JCOG0703, to explore feasibility of the laparoscopic distal gastrec-
tomy for cStage I gastric cancer in 2007. The incidence of anasto-
motic leakage and pancreatic fistula, the primary endpoint, was
much less at 1.7% (3 of 176 patients) than had been expected (40).
Reflecting this result, the Japanese Guidelines for the Treatment of
1066 The current state of stomach cancer surgery in the world

Gastric Cancer revised the position of laparoscopic distal gastrec-
tomy for cStage I gastric cancer in 2014 from a promising but
experimental treatment to an option in daily clinical practice.
However, laparoscopic surgery for more advanced gastric cancer
and laparoscopic total gastrectomy remain to be categorized as
experimental procedures that should best be evaluated in clinical
trials (14).
In 2009, the JCOG proceeded further to conduct a Phase III
trial, JCOG0912, to prove non-inferiority of the laparoscopic
approach in terms of 5-year survival rate compared with the open
approach (41), and completed recruitment of 920 patients with
cStage I cancer by 2015. However, the number of events is currently
estimated to be too small to statistically prove the non-inferiority.
Although there was an option proposed by the biostatisticians to
was 4.7% (4/86), Grade 3 or higher morbidity rate was 5.8% and
mortality was 0% (42). Thus, safety of the laparoscopic distal gas-
trectomy to treat advanced cancer was proven. The Phase III part is
still recruiting patients as of June 2016.
In fact, these consistent efforts to eventually integrate laparo-
scopic surgery into clinical practice were not swift enough to claim
Japan as the number one in this area of research. While the Japanese
investigators were struggling, the Korean investigators had been
more cooperative and completed accrual in two important large-
scale trials organized by the Korean Laparoscopy-Assisted Surgery
Society (KLASS). KLASS-01, an open versus laparoscopy trial for
cStage I cancer that is resectable by distal gastrectomy, was conducted
as a mega-trial involving 1416 patients. The safety and quality of life
data have already been analyzed, the laparoscopy group showing

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revise the study protocol and expand the sample size, several partici- lower complication rate (13.0% versus 19.9%, P = 0.001) (43).
pating surgeons voted against this idea, presumably because they Analysis of the final survival data are expected by the end of 2016.
have began to believe through their clinical experience that laparo- Subsequently, they conducted KLASS-02, another open versus
scopic distal gastrectomy for early gastric cancer is feasible, and felt laparoscopy Phase III trial for clinically T2∼T4a gastric cancer, resect-
able by distal gastrectomy, with 3-year relapse-free survival as the pri-
that it has become increasingly difficult to persuade a patient to
mary endpoint (44). This is also a large-scale trial with a sample size
cooperate by being randomized. Again, laparoscopic gastrectomy
of 1050, but the patient recruitment was prompt and has already ter-
had already been approved by the government back in 2006 and
minated in 2015. They also conducted a Phase II study to evaluate
cost reimbursed by the social insurance, and the number of laparo-
feasibility of laparoscopic total gastrectomy (KLASS-03) and success-
scopic distal gastrectomy performed by general surgeons outside of
fully recruited 170 patients from 17 institutions (45). These facts
the trial had been consistently on the rise by the time the JCOG trial
show the sheer strength of the Korean infrastructure in that the
had been ongoing (Fig. 3).
patients are concentrated in a small number of super high-volume
Under these circumstances, another group of more prominent
hospitals around Seoul. Once the members from dedicated centers
laparoscopic surgeons decided they could not wait for the next step
agree upon conducting a trial, recruitment of patients is conducted
until the results of the JCOG trial becomes available, and started a
quite effortlessly despite the ambitious sample size.
Phase II/III open versus laparoscopy trial for clinically T2~T4a/
The paucity of early-stage cancers in China relative to Korea and
N0~2 gastric cancer that can be resected by distal gastrectomy with
Japan encouraged surgeons in that country to attempt laparoscopic
D2 dissection (JLSSG0901). In the Phase II part looking at safety of
surgery for more advanced gastric cancer. Apparently, some Chinese
the laparoscopic approach in the treatment of advanced gastric can-
surgeons still managed to accumulate experience with early-stage
cer, the incidence of either anastomotic leakage or pancreatic fistula

laparoscopic distal gastrectomy

10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0

till 2015
Preliminary report from the first JCOG0703 JCOG0912
generation surgeons (33) till 2016
JLSSG0901

till 2015
KLASS-01 KLASS-02

Figure 3. The annual number of laparoscopic distal gastrectomy performed in Japan. Accrual time of several Japanese and Korean studies and trials related to
laparoscopic distal gastrectomy described in the text are shown underneath. The data are derived from a questionnaire survey conducted by the Japan Society
for Endoscopic Surgery, in which the questionnaire was sent to 2412 institutions that includes members of the society and the response retrieved from 1380
institutions.

cancer so that they did not feel too uncomfortable when applying the
laparoscopic approach to more advanced cancer. Thus, a randomized
open versus laparoscopic trial for advanced gastric cancer (cT2~4a,
cN0~3, M0, resectable by distal gastrectomy) was conducted in 2012
and accrual of 1056 patients was completed by the end of 2014 (46).
There was no significant difference between the two groups in post-
operative morbidity (15.2% in the laparoscopy group and 12.9% in
the open surgery group, P = 0.285) and mortality (0.4% in the laparo-
scopic group and 0% in the open surgery group, P = 0.249). The
3-year overall survival rate, the primary endpoint, will soon be avail-
able, and could become the first data from an adequately designed
Phase III open versus laparoscopy trials that show non-inferiority of
the laparoscopic approach to treat advanced gastric cancer.
While distal gastrectomy by the laparoscopic approach has been
extensively tested, challenging surgeons proceeded to conduct total
gastrectomy (47) and gradually extended the indication to more
advanced cancer, remnant cancer (48) and junctional cancer
(49,50). Laparoscopic gastrectomy that involves esophagojejunost-
omy is generally considered more demanding due to technical diffi-
culty in the totally laparoscopic anastomosis, and it is clear by
looking at the annual number of laparoscopic total gastrectomies
performed in Japan that an exponential increase in the number of
total/proximal gastrectomies performed began ~1 year after that of
distal gastrectomy (Fig. 4). The anastomosis can be completed either
by using a circular stapler, with the anvil head introduced either
orally (51,52) or from the esophageal stump (53), or by using linear
staplers (54–56). Alongside the KLASS-03 study, the JCOG is cur-
rently recruiting patients for a Phase II trial to evaluate the safety of
laparoscopic total/proximal gastrectomy (JCOG1401). Besides
results from these clinical trials, both retrospective and prospective
data comparing open versus laparoscopic total/distal surgery using
big data derived from the National Clinical Database will soon be
available in Japan for reference.
The place of robotic surgery
Recent development of robotic surgery as an option to facilitate
minimally invasive surgery deserves some comments. The Da Vinci
laparoscopic total + proximal gastrectomy
2500
2000
1500
1000
500
total gastrectomy
Figure 4. The annual number of laparoscopic total and proximal gastrectomy performed in Japan. The data are derived from a questionnaire survey conducted
by the Japan Society for Endoscopic Surgery, in which the questionnaire was sent to 2412 institutions that includes members of the society and the response
retrieved from 1380 institutions.
Jpn J Clin Oncol, 2016 , Vol. 46, No. 11 1067
system currently dominates the global market share of the master-
slave type robotic devices used for gastrointestinal cancer surgery.
This system has strengths such as EndoWrist equipped with add-
itional degrees of freedom, elimination of the fulcrum effect, high-
resolution three-dimensional images that can be magnified and
reduced human tremor, and facilitates surgeons to overcome several
shortcoming inherent to the laparoscopic approach (57). Decrease in
the incidence of surgical complications when compared with the lap-
aroscopic surgery has been reported for gastric cancer surgery from
a leading Japanese institution with experience of >200 cases (58). In
Japan, however, robotic surgery is approved by the government as a
treatment to be covered by the national insurance only for prostatec-
tomy and partial nephrectomy, as of 2016. The health insurance sys-
tem in that country requires not only the cost for surgery but also
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the entire cost for hospital admission, drugs and other expenses
related to surgery and preoperative and postoperative care included,
to be paid either by the institution or the patient, when any device
or drug that is not approved by the government is used during the
treatment. Institutions with particular ambition and strategic consid-
erations might take resolute action to either partially or totally cover
these costs (59), and only a handful of surgeons who are supported
by these strategic, wealthy or generous institutions could perform
Da Vinci surgery and accumulate sufficient experience to be able to
join a government approved and industry sponsored clinical trial.
That trial, approved by the Ministry of Health and Welfare in 2014,
is a one arm prospective study to explore benefits of the robotic sur-
gery, in which the hypothesis to prove is that the incidence of Grade
III postoperative complications in gastrectomy for cStage I/II gastric
cancer be reduced to 3.2% as opposed to 6.5% which has been
observed in the corresponding surgery performed laparoscopically
in three leading participating institutions. It is hoped that if the pri-
mary endpoint is met in that trial, the government would approve
the use of Da Vinci system at institutions that fulfill several criteria
demonstrating prior experiences with the robotic surgery and
expertize in the laparoscopic surgery. Rather sarcastically, only the
top-notch surgeons who would comfortably perform gastrectomy
laparoscopically without relying on this expensive system are quali-
fied to use it in Japan at this moment.
proximal gastrectomy
1068 The current state of stomach cancer surgery in the world

In South Korea, the health insurance system is more flexible in
that only the cost needed to operate the Da Vinci system need to be
covered by the patient while other expenses during the hospital
admission can be covered by the social insurance. This prompted
laparoscopic surgeons to perform robot-assisted surgery upon
request from the patients, and the greatest number of robot-assisted
gastrectomy in the world has so far been performed in Korea.
Several Japanese surgeons have stayed at Yonsei University, one of leading
Korean institutions in robotic surgery, to learn the technique (60).
A non-randomized prospective study that compared the robotic
with laparoscopic surgery in that country has shown morbidity to
be extremely low in both approaches, but the robotic surgery needed
longer operating time and was significantly more expensive (61).
Perhaps one of the reasons for difficulty in detecting benefits of the
simulators, it may be necessary for them to take full advantage of the
laparoscopic approach in that all participants in surgery can share
the view of the operator and that videos are invariably recorded for
repeated viewing and discussion. Easier access to the robotic surgery
and more frequent opportunities for training with that modality will
likely be helpful under such circumstances, given the shorter learning
curve for acquisition of relevant surgical skills (64).
The issue of limited surgery for early gastric
cancer
Total gastrectomy and distal gastrectomy that dissects two-thirds or
more of the stomach are the only types of gastrectomy that has been

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robotic surgery is similar to the situation in Japan. The Korean sur-
geons who attempted robotic surgery had already acquired profi-
ciency in laparoscopic maneuvers through extensive training and
experience in laparoscopic surgery, again taking the advantage of
the greatest patient resource per a selected surgeon in a society
where cancer patients are efficiently centralized to super high-
volume hospitals (2,62).
In the Western countries, introduction of the laparoscopic
approach may have been hindered by the paucity of resectable gastric
cancer (early-stage gastric cancer in particular), a higher proportion
of obese and morbid patients, and the predominance of lesions
located in the proximal stomach. Despite efforts for centralization,
surgeons in the West will need to acquire surgical skills through
hands-on training with much smaller number of patients than in the
Far East. Furthermore, these patients often suffer from bulky cancer
that may have been heavily pretreated. Through centralization and
surgical training, they have successfully decreased the surgical mor-
bidity and mortality rates in open surgery. However, introduction of
the laparoscopic approach has not been easy and, according to the
national administrative database in UK, the rate of laparoscopic
approach among all patients who were operated for gastric cancer
was 16.1% in 2009 (63). Besides acquiring laparoscopic skills
through participating in more common and less demanding types of
surgery as well as training themselves with box trainers and virtual
defined as standard gastrectomy in the Japanese Gastric Cancer
Treatment Guidelines (14), and has been performed worldwide.
Proximal gastrectomy for cancer of the upper-third stomach and
pylorus-preserving gastrectomy (PPG) for cancer of the middle-third
stomach are the two commonly performed surgical procedures that
fall into the category of limited surgery (Fig. 5). These, accompanied
with less extensive D1 or D1+ lymphadenectomy, could replace the
standard gastrectomy in cases of early gastric cancer, and have been
conducted mainly in Japan and Korea where early cancers are
prevalent. However, advantage of limited surgery over standard sur-
gery in terms of improvements in quality of life or nutritional status
has not been robustly shown by formal randomized trials.
Proximal gastrectomy has been considered as an option for
patients with junctional cancer (65) and early cancer of the upper-
third stomach (14). This procedure mandates preservation of blood
supply to the distal stomach, namely the right gastric artery and suf-
ficient length of the right gastroepiploic artery, meaning that dissec-
tion of lymph node Nos. 5, 6 must be abandoned and dissection of
the distal portions of Nos. 4d and 3b will have to be compromised.
In addition, some surgeons prefer meticulous surgical technique to
preserve the hepatic branch from the anterior vagal trunk and the
celiac branch from the posterior vagal trunk. Since the pyloric
branch which is considered to control the pyloric ring bifurcates
from the hepatic branch, either pyloric bougie or pyloroplasty might

(a)
4sb (b)
4d 4sb

4sa

6
3 3a 2
1 1
7 7
9 9
8a 8a 11p

Pylorus-preserving Proximal gastrectomy

gastrectomy

Figure 5. Figure showing pylorus-preserving gastrectomy (Fig. 5a) and proximal gastrectomy (Fig. 5b) with lymph nodes to be dissected (dissection of lymph
node stations in blue is needed for D1 dissection and lymph node stations in orange for D1+ dissection). The figures are taken from the Japanese Gastric
Cancer Treatment Guidelines version 4 (14).

be needed in the event that the hepatic branch is sacrificed. Whether
the patients really benefit from receiving this type of resection
instead of total gastrectomy could be rather controversial, given the
high incidence of severe reflux esophagitis that had been observed
among those who underwent esophagogastrectomy (66). In add-
ition, patients who are treated by proximal gastrectomy has been
considered to be at risk of developing cancer of the gastric remnant,
since cancer of the distal stomach had been more commonly seen in
the Asian patients compared with that of the proximal stomach.
Currently, there are two options for preventing the reflux
esophagitis. One is addition of the anti-reflux procedure after the
esophagogastrectomy. The double flap technique has become par-
ticularly popular in Japan (67), but size of the remnant stomach will
have to be relatively large to be eligible for this type of reconstruc-
tion. Another option is to interpose a short jejunal segment between
the esophagus and the gastric remnant (68). In a relatively large
single-institutional study 65 patients who underwent proximal gas-
trectomy reconstructed by jejunal interposition were compared with
117 patients who underwent total gastrectomy with Roux-Y recon-
struction for clinically T1 cancer. Significant differences in body
weight loss, decline in serum hemoglobin and incidence of Dumping
syndrome were observed and proximal gastrectomy was considered
as beneficial (69). More recently, a double-tract reconstruction,
which is more easily performed by the laparoscopic approach, has
gained popularity (70).
As a tool to conduct more convincing comparisons between various
types of gastrectomy, integrated questionnaires for assessment of living
status and quality of life, the Post-Gastrectomy Symptom Rating Scale
(PGSAS)-45, was compiled by the Japanese Postgastrectomy Syndrome
Working Party (71). In the process of validating this questionnaire,
the working party conducted a multi-institutional study in which the
health-related quality of life was measured at one time point
>12 months after various types of surgery for Stage I gastric cancer.
Subsequently, several comparisons between various subsets of patients
were conducted from data obtained in this study. In a comparison
between proximal gastrectomy (n = 193) and total gastrectomy
(n = 393), significant differences were observed in the magnitude of
body weight loss and subscales looking at necessity for additional
meals, diarrhea and Dumping syndrome, all in favor of proximal gas-
trectomy (72). Another study looking only at 115 patients who under-
went proximal gastrectomy followed by esophagogastrectomy
identified large remnant stomach, addition of anti-reflux procedure,
and the use of pyloric bougie as predictors of better quality of life (73).
Further prospective studies using this or other tools (74,75) to evaluate
health-related quality of life with focus on the postgastrectomy syn-
drome are warranted to confirm advantage of performing proximal
gastrectomy and to find optimal method of reconstruction.
PPG has been increasingly used in surgery for early-stage cancer
of the middle stomach (76). In this procedure, a short segment of
the antrum (usually 2–4 cm), often referred to as a pyloric cuff, is
preserved with the pyloric ring. In addition to preservation of the
right gastric artery, increasing attention has been paid to the anat-
omy of the infrapyloric artery which could be preserved without
compromising the removal of No. 6 lymph nodes if it bifurcates
from the anterior superior pancreaticoduodenal artery or gastroduo-
denal artery. It will have to be sacrificed if it bifurcates from the
right gastroepiploic artery as seen in 23% of the patients (77), unless
a surgeon decides to divide the right gastroepiploic artery distal to
the bifurcation. Anatomy of the infrapyloric veins have also been
studied (78). Preservation of the infrapyloric vessels, where possible,
is considered to decrease the incidence of gastric stasis, a common
Jpn J Clin Oncol, 2016 , Vol. 46, No. 11 1069
complication after the PPG occurring in around 8% of the patients (79).
In addition, preservation of the hepatic branch from the anterior vagal
trunk is considered mandatory to preserve the pyloric function.
A single-institution study comparing 116 patients treated by lap-
aroscopic PPG with 176 patients treated by laparoscopic distal gas-
trectomy was reported from Korea and revealed significantly lower
incidence of surgical complications in the PPG group (7.8% versus
17%, P = 0.023), with the exception of delayed gastric emptying. In
addition, better nutritional status in terms of serum protein and
albumin and lower incidence of gallstone were observed for the PPG
group (80). A comparison of health-related quality of life between
patients who received PPG and those treated with distal gastrectomy
using data from the aforementioned validation study of the PGSAS-
45 revealed significant difference in favor of PPG in diarrhea sub-
Downloaded from https://academic.oup.com/jjco/article/46/11/1062/2445898 by guest on 23 November 2020
scale, dumping subscale and frequency of additional meals (81). In
addition, patients with larger proximal gastric remnant benefitted
from superior quality of life in terms of several subscales of the
PGSAS-45 questionnaires (82). Since convincing data from a pro-
spective trial remain lacking, KLASS-04 study was launched in
Korea to evaluate LAPPG in comparison with the laparoscopy-
assisted distal gastrectomy (45).
Unfortunately, the issue of limited surgery has not aroused suffi-
cient interest from the Western investigators, fundamentally because
of paucity of cStage I cancers for whom the extent of lymphadenect-
omy could be compromised. In addition, at least some Western sur-
geons are more interested in avoidance of major gastrectomy
through sentinel node navigation (31), which is easier to understand
as a concept than various limited surgery procedures which are not
necessarily easy to perform and are currently not supported by robust
evidence regarding improvements in postoperative quality of life.
Conclusion
Various efforts to develop optimal surgery to cure advanced resect-
able gastric cancer converged to D2 dissection and D2 without
splenectomy in case of total gastrectomy. Although not a focus of
this review article, this surgery will have to be combined with
evidence-based adjuvant therapy to achieve the best possible out-
come. On the other hand, high proportion of early-stage cancer
diagnosed in Japan and Korea led to development of limited surgery
options although benefits of these procedures have not yet been
robustly proven in prospective studies. Hard evidence in support of
laparoscopic surgery has begun to accumulate, and robotics may be
helpful to apply the minimally invasive approach to perform more
complex surgery in the future, pending the issue of high cost.
Acknowledgement
The author received research grant from Johnson & Johnson and Covidien
Japan and lecture fee from Johnson & Johnson outside of the submitted work.
Conflict of interest statement
None declared.
References
1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality
worldwide: sources, methods and major patterns in GLOBOCAN 2012.
Int J Cancer 2015;136:E359–86.
1070 The current state of stomach cancer surgery in the world
2. Kodera Y. Extremity in surgeon volume: Korea may the place to go if you
want to be a decent gastric surgeon. Gastric Cancer 2016;19:323–5.
3. Wu CW, Hsiung CA, Lo SS, et al. Nodal dissection for patients with gas-
tric cancer: a randomized controlled trial. Lancet Oncol 2006;7:309–15.
4. Averbach AM, Jacquet P. Strategies to decrease the incidence of intra-
abdominal recurrence in resectable gastric cancer. Br J Surg 1996;
83:726–33.
5. Maehara Y, Yamamoto M, Oda S, et al. Cytokeratin-positive cells in
bone marrow for identifying distant micrometastasis of gastric cancer.
Br J Cancer 1996;73:83–7.
6. Mimori K, Fukagawa T, Kosaka Y, et al. A large-scale study of MT1-
MMP as a marker for isolated tumor cells in peripheral blood and bone
marrow in gastric cancer cases. Ann Surg Oncol 2008;15:2934–42.
7. Nashimoto A, Akazawa K, Isobe Y, et al. Gastric cancer treated in 2002
in Japan: 2009 annual report of the JGCA nationwide registry. Gastric
Cancer 2013;16:1–27.
8. Yoshikawa K, Maruyama K. Characteristics of gastric cancer invading to
the proper muscle layer: with special reference to mortality and cause of
death. Jpn J Clin Oncol 1985;15:499–503.
9. Koga S, Kaibara N, Iitsuka Y, Kudo H, Kimura A, Hiraola H. Prognostic
significance of intraperitoneal free cancer cells in gastric cancer patients.
J Cancer Res Clin Oncol 1984;108:236–8.
10. Afaneh C, Levy A, Selby L, et al. Ex vivo lymphademectomy during gas-
trectomy for adenocarcinoma optimizes lymph node yield. J Gastrointest
Surg 2016;20:165–71.
11. Japanese Gastric Cancer Association. Japanese classification of gastric
carcinoma: 3rd english edition. Gastric Cancer 2011;14:101–12.
12. Fukutomi H, Sakita T. Analysis of early gastric cancer cases collected
from major hospitals and institutes in Japan. Jpn J Clin Oncol 1984;14:
169–79.
13. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node
metastasis from early gastric cancer: estimation with a large number of
cases at two large centers. Gastric Cancer 2000;3:219–25.
14. Japan Gastric Cancer Association. Japanese guidelines for treatment of
gastric cancer, 4th edition. Gastric Cancer 2016, in press.
15. Bollschweiler E, Boettcher K, Hoelscher AH, et al. Preoperative assess-
ment of lymph node metastases in patients with gastric cancer: evaluation
of the Maruyama Computer program. Br J Surg 1992;79:156–60.
16. Sasako M, McCulloch P, Kinoshita T, Maruyama K. New method to
evaluate the therapeutic value of lymph node dissection for gastric cancer.
Br J Surg 1995;82:346–51.
17. Wanebo HJ, Kennedy BJ, Chmiel J, Steele G, Winchester D, Osteen R.
Cancer of the stomach. A patient care study by the American College of
Surgeons. Ann Surg 1993;218:583–92.
18. Bonenkamp JJ, Hermans J, Sasako M, Van de Velde CJH. Extended
lymph node dissection for gastric cancer. N Engl J Med 1999;340: 908–
14.
19. Cuschieri A, Weeden S, Fielding J, et al. Patient survival after D1 and D2
resections for gastric cancer: long-term results of the MRC randomized
surgical trial. Br J Cancer 1999;79:1522–30.
20. Songun I, Putter H, Kranenbarg EM, Sasako M, van de Velde CJ.
Surgical treatment of gastric cancer: 15-year follow-up results of the ran-
domised nationwide Dutch D1D2 trial. Lancet Oncol 2010;11:439–49.
21. Coupland VH, Lagergren J, Luchtenborg M, et al. Hospital volume, pro-
portion resected and mortality from oesophageal and gastric cancer: a
population-based study in England, 2004–2008. Gut 2013;62:961–6.
22. Cuschieri A, Hanna GB. Meta-analysis of D1 versus D2 gastrectomy for
gastric adenocarcinoma: let us move on to another era. Ann Surg 2014;
259:e90.
23. Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or
with para-aortic nodal dissection for gastric cancer. N Engl J Med 2008;
359:453–62.
24. Yoshikawa T, Sasako M, Yamamoto S, et al. Phase II study of neoadjuvant
chemotherapy and extended surgery for locally advanced gastric cancer.
Br J Surg 2009;96:1015–22.
25. Tsuburaya A, Mizusawa J, Tanaka Y, et al. Neoadjuvant chemotherapy
with S-1 and cisplatin followed by D2 gastrectomy with para-aortic
lymph node dissection for gastric cancer with extensive lymph node
metastasis. Br J Surg 2014;101:653–60.
26. Roviello F, Pedrazzani C, Marrelli D, et al. Super-extended (D3) lymphade-
nectomy in advanced gastric cancer. Eur J Surg Oncol 2010;36:439–46.
27. Sano T, Sasako M, Mizusawa J, et al. Randomized controlled trial to
evaluate splenectomy in total gastrectomy for proximal gastric carcinoma
(JCOG0110). Ann Surg 2016, in press.
28. Ohgami M, Otani Y, Kumai K, Kubota T, Kim YI, Kitajima M.
Curative laparoscopic surgery for early gastric cancer: five years
experience. World J Surg 1999;23:187–92.
29. Hiki N, Yamamoto Y, Fukunaga T, et al. Laparoscopic and endoscopic
cooperative surgery for gastrointestinal stromal tumor dissection. Surg
Endosc 2008;22:1729–35.
30. Mitsui T, Niimi K, Yamashita H, et al. Non-exposed endoscopic
wall-inversion surgery as a novel partial gastrectomy technique. Gastric
Downloaded from https://academic.oup.com/jjco/article/46/11/1062/2445898 by guest on 23 November 2020
Cancer 2014;17:594–9.
31. Kitagawa Y, Takeuchi H, Takagi Y, et al. Sentinel node mapping for gas-
tric cancer: a prospective multicenter trial in Japan. J Clin Oncol 2013;
31:3704–10.
32. Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted
Billroth I gastrectomy. Surg Laparosc Endosc 1994;4:146–8.
33. Kitano S, Shiraishi N, Uyama I, Sugihara K, Tanigawa N, Japanese
Laparoscopic Surgery Study Group. A muliticenter study on oncologic
outcome of laparoscopic gastrectomy for early cancer in Japan. Ann Surg
2007;245:68–72.
34. Fujiwara M, Kodera Y, Misawa K, et al. Longterm outcomes of early-
stage gastric carcinoma patients treated with laparoscopy-assisted
surgery. J Am Coll Surg 2008;206:138–43.
35. Fujiwara M, Kodera Y, Kasai Y, et al. Laparoscopy-assisted distal gas-
trectomy with systemic lymph node dissection for early gastric carcinoma:
a review of 43 cases. J Am Coll Surg 2003;196:75–81.
36. Park DJ, Han S-U, Hyung WJ, et al. Long-term outcomes after laparoscopy-
assisted gastrectomy for advanced gastric cancer: a large-scale multicenter
retrospective study. Surg Endosc 2012;26:1548–33.
37. Shinohara T, Satoh S, Kanaya S, et al. Laparoscopic versus open D2 gas-
trectomy for advanced gastric cancer: a retrospective cohort study. Surg
Endosc 2013;27:286–94.
38. Mochizuki Y, Kodera Y, Fujiwara M, et al. Single-institute
prospective trial of laparoscopy-assisted distal gastrectomy with
systemic lymph node dissection for early gastric carcinoma. Gastric
Cancer 2012;15: 124–30.
39. Yoshikawa T, Cho H, Rino Y, et al. A prospective feasibility and safety
study of laparoscopy-assisted distal gastrectomy for clinical stage I gastric
cancer initiated by surgeons with much experience of open gastrectomy
and laparoscopic surgery. Gastric Cancer 2013;16:126–32.
40. Katai H, Sasako M, Fukuda H, et al. Safety and feasibility of
laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dis-
section for clinically stage I gastric cancer: a multicenter phase II trial
(JCOG 0703). Gastric Cancer 2010;13:238–44.
41. Nakamura K, Katai H, Mizusawa J, et al. A phase III study of
laparoscopy-assited versus open distal gastrectomy with nodal dissection
for clinical stage IA/IB gastric cancer (JCOG0912). Jpn J Clin Oncol
2013;43:324–7.
42. Inaki N, Etoh T, Ohyama T, et al. A multi-institutional, prospective,
phase II feasibility study of laparoscopy-assisted distal gastrectomy with
D2 lymph node dissection for locally advanced gastric cancer. World J
Surg 2015;39:2734–41.
43. Kim W, Kim HH, Han SU, et al. Gastrectomy for stage I gastric cancer:
short-term outcomes from a multicenter randomized controlled trial
(KLASS-01). Ann Surg 2016;263:28–35.
44. Hur H, Lee HY, Lee HJ, et al. Efficacy of laparoscopic subtotal gastrec-
tomy with D2 lymphadenectomy for locally advanced gastric cancer: the
protocol of the KLASS-02 multicenter randomized controlled clinical trial.
BMC Cancer 2015;15:335.
45. Kim K-H, Kim S-H, Kim M-C. How much progress has been made in
minimally invasive surgery for gastric cancer in Korea? A viewpoint from
Korean prospective clinical trials. Medicine (Baltimore) 2014;93:e233.

46.Hu Y, Huang C, Sun Y, et al. Morbidity and mortality of laparoscopic
versus open D2 distal gastrectomy for advanced gastric cancer: a rando-
mized controlled trial. J Clin Oncol 2016;34:1350–7.
47. Shinohara T, Kanaya S, Taniguchi K, Fujita T, Tanaga K, Uyama I.
Laparoscopic total gastrectomy with D2 lymph node dissection for gastric
cancer. Arch Surg 2009;144:1138–42.
48. Tsunoda S, Okabe H, Tanaka E, et al. Laparoscopic gastrectomy
for rem- nant gastric cancer: a comprehensive review and case series.
Gastric Cancer 2016;19:287–92.
49.Noshiro H, Miyasaka Y, Okashi M, Iwasaki H, Ikeda O, Uchiyama A.
Minimally invasive esophagogastrectomy for esophagogastric junctional
cancer. Ann Thorac Surg 2012;93:214–20.
50. Takiguchi S, Miyazaki Y, Shinno N, et al. Laparoscopic
mediastinal dis- section via an open left diaphragm approach for
advanced Siewert type II adenocarcinoma. Surg Today 2016;46:129–34.
51. Kunisaki C, Makino H, Oshima T, et al. Application of the transorally
inserted anvil (OrVil) after laparoscopy-assisted total gastrectomy. Surg
Endosc 2011;25:1300–05.
52. LaFemina J, Vinuela EF, Schattner MA, Gerdes H, Strong VE.
Esophagojejunal reconstruction after total gastrectomy for gastric cancer
using a transorally inserted anvil delivery system. Ann Surg Oncol 2013;
20:2975–83.
53. Wada N, Kurokawa Y, Takiguchi S, et al. Feasibility of laparoscopy-
assisted total gastrectomy in patients with clinical stage I gas- tric cancer.
Gastric Cancer 2014;17:137–40.
54. Inaba K, Satoh S, Ishida Y, et al. Overlap method: novel intracorporeal
esophagojejunostomy after laparoscopic total gastrectomy. J Am Coll
Surg 2010;211:25–9.
55. Nagai E, Ohuchida K, Nakata K, et al. Feasibility and safety of intracor-
poreal esophagojejunostomy after laparoscopic total gastrectomy: inverted
T-shaped anastomosis using linear staplers. Surgery 2013;153:732–738.
56. Okabe H, Obama K, Tsunoda S, Tanaka E, Sakai Y. Advantage of com-
pletely laparoscopic gastrectomy with linear stapled reconstruction: a
long-term follow-up study. Ann Surg 2014;259:109–16.
57. Terashima M, Tokunaga M, Tanizawa Y, et al. Robotic surgery for gas-
tric cancer. Gastric Cancer 2015;18:449–57.
58. Suda K, Man-I M, Ishida Y, Kawamura Y, Satoh S, Uyama I. Potential
advantages of robotic radical gastrectomy for gastric adenocarcinoma in
comparison with conventional laparoscopic approach: a single institu-
tional retrospective comparative study. Surg Endosc 2015;29:673–85.
59. Tokunaga M, Sugisawa N, Kondo J, et al. Early phase II study of robot-
assisted distal gastrectomy with nodal dissection for clinical stage IA
gastric cancer. Gastric Cancer 2013;17:542–547.
60. Okumura N, Son T, Kim YM, et al. Robotic gastrectomy for
elderly gas- tric cancer patients: comparisons with robotic gastrectomy
in younger patients and laparoscopic gastrectomy in the elderly. Gastric
Cancer 2015, Epub ahead of print.
61. Kim HI, Han SU, Yang HK, et al. Multicenter prospective comparative
study of robotic versus laparoscopic gastrectomy for gastric adenocarcinoma.
Ann Surg 2016;263:103–9.
62. Kim CY, Nam BH, Cho GS, et al. Learning curve for gastric cancer sur-
gery based on actual survival. Gastric Cancer 2016;19:631–638.
63. Mamidanna R, Almoudaris AM, Bottle A, Aylin P, Faiz O, Hanna GB.
National outcomes and uptake of laparoscopic gastrectomy for cancer in
England. Surg Endosc 2013;27:3348–58.
64.Zhou J, Shi Y, Qian F, et al. Cumulative summation analysis of learning
curve for robot-assisted gastrectomy in gastric cancer. J Surg Oncol 2015;
111:760–767.
65. Kodera Y, Yamamura Y, Shimizu Y, et al. Adenocarcinoma of the gastroeso-
phageal junction in Japan: relevance of Siewert↩s classification applied
to 177 cases resected at a single institution. J Am Coll Surg 1999;189:594–
601.
Jpn J Clin Oncol, 2016 , Vol. 46, No. 11 1071
66.Nakamura M, Nakamori M, Ojima T, et al. Reconstruction after prox-
imal gastrectomy for early gastric cancer in the upper third of the sco-
mach: An analysis of our 13-year experience. Surgery 2014;156:57–63.
67. Kuroda S, Nishizaki M, Kikuchi S, et al. Double flap technique as an
anti-reflux procedure in esophagogastrostomy after proximal gastrec-
tomy. J Am Coll Surg. 2016;233:e7–e13.
68. Katai H, Sano T, Fukagawa T, Shinohara H, Sasako M. Prospective
study of proximal gastrectomy for early gastric cancer in the upper third
of the stomach. Br J Surg 2003;90:850–853.
69. Ohashi M, Morita S, Fukagawa T, Oda I, Kushima R, Katai H.
Functional advantages of proximal gastrectomy with jejunal interposition
over total gastrectomy with Roux-en-Y esophagojejunostomy for early
gastric cancer. World J Surg 2015;39:2726–33.
70. Yang K, Bang HJ, Almadani ME, et al. Laparoscopic proximal gastrec-
tomy with double-tract reconstruction by intracorporeal anastomosis with
Downloaded from https://academic.oup.com/jjco/article/46/11/1062/2445898 by guest on 23 November 2020
linear staplers. J Am Coll Surg 2016;222:e39–45.
71. Nakada K, Ikeda M, Takahashi M, et al. Characteristics and clinical rele-
vance of postgastrectomy syndrome assessment scale (PGSAS)-45: newly
developed integrated questionnaires for assessment of living status and
quality of life in postgastrectomy patients. Gastric Cancer 2015;18: 147–
58.
72. Takiguchi N, Takahashi M, Ikeda M, et al. Long-term quality-of-life com-
parison of total gastrectomy and proximal gastrectomy by Postgastrectomy
Syndrome Assessment Scale (PGSAS)-45: a nationwide multi-institutional
study. Gastric Cancer 2015;18:407–16.
73. Inada T, Yoshida M, Ikeda M, et al. Evaluation of QOL after proximal
gastrectomy using a newly developed assessment scale (PGSAS-45).
World J Surg 2014;38:3152–62.
74. Nakamura M, Hosoya Y, Umeshita K, et al. Postoperative quality of life:
development and validation of the ‘Dysfunction After Upper
Gastrointestinal Surgery’ scoring system. J Am Coll Surg 2011;213:
508–14.
75. Honda M, Wakita T, Onishi Y, et al. Development and validation of a
symptom scale to evaluate postoperative patients with esophagogastric
cancer. J Am Coll Surg 2014;219:895–903.
76. Morita S, Katai H, Saka M, Fukagawa T, Sano T, Sasako M. Outcome of
pylorus-preserving gastrectomy for early gastric cancer. Br J Surg 2008;
95:1131–35.
77. Haruta S, Shinohara H, Ueno M, Udagawa H, Sakai Y, Uyama I.
Anatomical consideration of the infrapyloric artery and its associated
lymph nodes during laparoscopic gastric cancer surgery. Gastric Cancer
2015;18:876–80.
78. Nishizawa N, Yamashita K, Shinohara H, Sakuramoto S, Hosoda K,
Watanabe M. Anatomical knowledge for the infra-pyloric vein preserva-
tion during the laparoscopy-assisted pylorud-preserving gastrectomy. Dig
Surg 2016;33:363–70.
79. Nunobe S, Hiki N, Fukunaga T, et al. Laparoscopy-assisted pylorus-pre-
serving gastrectomy: preservation of vagus nerve and infrapyloric blood
flow induces less stasis. World J Surg 2007;31:2335–40.
80. Suh YS, Han DS, Kong SH, et al. Laparoscopy-assisted pylorus-
preserving gastrectomy is better than laparoscopy-assisted distal
gastrectomy for middle-third early gastric cancer. Ann Surg
2014;259:485–93.
81. Fujita J, Takahashi M, Urushihara T, et al. Assessment of postoperative
quality of life following pylorus-preserving gastrectomy and Billroth-I
gastrectomy in gastric cancer patients: results of the nationwide
postgastrectomy syndrome assessment study. Gastric Cancer 2016;19:
302–11.
82. Namikawa T, Hiki N, Kinami S, et al. Factors that minimize
postgastrect- omy symptoms following pylorus-preserving gastrectomy:
assessment using a newly developed scale (PGSAS-45). Gastric Cancer
2015;18: 397–406
1 MainTopic
Gastric cancer is a disease with aggressive biology, and is known to eventually
disseminate simultaneously by several metastatic routes, creating a mixed pattern of
treatment failure that is considered char- acteristic of the disease (4). While detection of
micrometastases and isolated cancer cells in the bone marrow (5) or in the form of circu-
lating tumor cells (6) have been reported even in early-stage cancer, clinical relevance of
these cells along with whether they indeed are representing viable cancer cells remain
questionable, given the excel- lent long-term survival of patients with early cancer who
underwent curative resection (7). According to a large case series, hematogen- ous
metastases are occasionally observed once cancer invades into the proper muscle layer (8),
and the incidence of peritoneal metasta- ses through dissemination directly from the
serosal surface rise abruptly once cancer invades the serosa (9).In contrast, cancer cells
spread through the lymphatics even dur- ing relatively early stages. In Japan, it has for a
long time been cus- tomary that surgeons who took part in surgery perform ex-vivo lymph
node retrieval (10). In other words, they scrutinize the resected specimens after surgery
and harvest lymph nodes from the adipose tissues that were removed en bloc with the
stomach

2 Support
Gastric cancer occurs due to genetic changes (Mutations ) in stomach cells, which
cause these cells to grow abnormally and out of control. These cells are called cancer
cells.

3 Prevention
These facts show the sheer strength of the Korean infrastructure in that the
patients are concentrated in a small number of super high-volume hospitals around Seoul.
Once the members from dedicated centers agree upon conducting a trial, recruitment of
patients is conducted quite effortlessly despite the ambitious sample size. The paucity of
early-stage cancers in China relative to Korea and Japan encouraged surgeons in that
country to attempt laparoscopic surgery for more advanced gastric cancer. Apparently,
some Chinese surgeons still managed to accumulate experience with early-stage cancer
so that they did not feel too uncomfortable when applying the laparoscopic approach to more
advanced cancer.