REVIEW ARTICLES

e-ISSN 1643-3750
© Med Sci Monit, 2019; 25: 3537-3541
DOI: 10.12659/MSM.916475

Received:
Accepted:
2019.03.25
2019.04.23 Recent Advances in the Surgical Treatment of
Published: 2019.05.13
Advanced Gastric Cancer: A Review
Authors’ Contribution: AEF Zhaoyang Tan Department of General Surgery, The Second Xiangya Hospital of Central South
Study Design A University, Changsha, Hunan, P.R. China
Data Collection B
Statistical Analysis C
Data Interpretation D
Manuscript Preparation E
Literature Search F
Funds Collection G

Corresponding Author: Zhaoyang Tan, e-mail: [email protected]

Source of support: Self financing

Gastric cancer is a common malignancy with a poor prognosis, and surgical treatment remains the first-line
approach to treatment to provide a cure. Despite advances in surgical techniques, radiotherapy, chemother-
apy, and neoadjuvant therapy, gastric cancer remains the second leading cause of cancer death worldwide.
Although the 5-year survival rate of early gastric cancer can reach >90%, due to the low early diagnosis rate,
most patients present with advanced-stage gastric cancer. Therefore, there has been increasing interest in im-
proving surgical treatment of advanced gastric cancer. Lymph node dissection is an important part of the sur-
gical treatment of advanced gastric cancer due to the high incidence of lymph node metastasis. Although pro-
spective studies have confirmed the safety and feasibility of laparoscopic surgery for early gastric cancer, the
relevant treatment models of advanced gastric cancer still need to be further explored and validated. This re-
view aims to provide an update on the recent advances in the surgical treatment of advanced gastric cancer.

MeSH Keywords: Laparoscopes • Lymph Node Excision • Stomach Neoplasms

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REVIEW ARTICLES Surgical treatment of advanced gastric cancer
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Background of lymph nodes (D1+a) and the simultaneous dissection of

lymph nodes in groups 7, 8a and 9 D1 lymph nodes (D1+b).
Worldwide, gastric cancer is the fourth most common cancer If six groups of lymph nodes are found to contain metastases,
and the second leading cause of cancer-related mortality and is then the dissection that removes 14v lymph nodes is called
associated with high morbidity [1]. The etiology and pathogen- D2+ 14v. According to the latest guidelines, if cancer invades
esis of gastric cancer remain to be established, and although the duodenum, the lymph nodes behind the pancreatic head
some causal factors have been identified, primary prevention (13 groups) should be dissected and is defined as D2+13.
remains a challenge [2]. Currently, there are no screening meth-
ods to detect gastric cancer, and because patients with early Inaki et al. suggested that D1+a dissection was only suitable
gastric cancer are usually symptom-free, there is a low rate for early gastric cancer in which the tumor was located in the
of early diagnosis of gastric cancer. Therefore, most patients distal stomach. D1+b dissection is suitable for the treatment
(>70%) present with advanced gastric cancer [3]. of early gastric cancer in the proximal stomach, but this type
of lymph node dissection may not be suitable for the treat-
Epidemiological studies have shown that the incidence of ment of advanced gastric cancer [10]. To address the ques-
gastric cancer in young people is gradually increasing [4]. tion regarding what extent of lymph node dissection is more
Therefore, it is particularly important to improve surgical treat- beneficial for patients with gastric cancer, Songun et al. [11]
ment options for advanced gastric cancer. There has been re- showed in a 15-year follow-up study, that the local recurrence
cent progress in improving medical and surgical technology, rate for patients undergoing D2 lymph node dissection was
and increased understanding of the pathogenesis of gastric significantly lower than that of patients undergoing D1 re-
cancer has resulted in approaches to the prevention of gas- section, indicating that increasing lymph node dissection had
tric cancer, and the development of targeted therapies [5]. survival benefits. However, Degiuli et al. performed a further
However, despite the rapid development of radiotherapy, stratified study that showed that D2 lymph node dissection
chemotherapy, and immunotherapy, surgical resection remains did not improve the 5-year survival rate for patients with T1
the only possible cure for gastric cancer [6–8]. Complete tumor gastric cancer [12]. In contrast, the 5-year survival rate of D2
resection and lymph node dissection combined with neoad- lymph node dissection in patients with T2–T4 gastric cancer was
juvant chemotherapy and postoperative adjuvant radiother- greater than that in the D1 group (59% vs. 8%) [12]. In 2012,
apy and chemotherapy have been shown to significantly im- Seevaratnam et al. published a meta-analysis of D1 compared
prove the postoperative survival time of patients with gastric with D2 lymph node dissection and analyzed patient outcome
cancer [9]. In particular, for the surgical treatment of gastric in five randomized controlled trials [13]. Meta-analysis showed
cancer, there continue to be studies that refine and compare there was no statistical difference in the 5-year survival rate
open and laparoscopic gastric surgery [10]. This review aims of patients with T1-T2 (55.4% in the D1 group and 52.3% in
to provide an update on the recent advances in the surgical the D2 group) (P=0.46) [13]. For patients with a higher T stage
treatment of advanced gastric cancer. (T3–4), there was a trend towards survival benefits in favor of
D2 (13.5% for D1 and 19.5% for D2) [13].

The Extent of Lymph Node Dissection in In a phase II trial conducted by the Japan Clinical Oncology
Advanced Gastric Cancer Group (JCOG), patients with locally advanced gastric cancer
and paragastric lymph node metastases and/or paraaortic me-
Lymph node dissection, performed during surgical resection tastases received neoadjuvant chemotherapy (S-1 plus cispla-
for gastric cancer is used for staging but also has an impor- tin), followed by extended dissection of abdominal para-aortic
tant impact on patient prognosis. D1, D2, and D3 gastrectomy lymph nodes (16 groups) [14]. The overall 3-year and 5-year
for gastric cancer include the perigastric Group 1, Group 2, survival rates were 59% and 53%, respectively [14]. Based on
and Group 3 lymph nodes, respectively. The current standard these results, Japanese surgeons now suggest that D2 gastrec-
of care for curative surgery for gastric cancer is for D2 gas- tomy plus para-aortic lymph node dissection after neoadjuvant
trectomy. Lymph node dissection is performed to determine chemotherapy may improve outcome in advanced gastric can-
the extent of lymph node involvement with metastases and cer with positive lymph nodes or extensive metastasis of N2
to improve outcome from surgery. The benefit of lymph node lymph nodes [15]. For lymph node dissection and prophylactic
dissection beyond D2 gastrectomy for advanced gastric re- splenectomy, JCOG conducted the 0110 clinical study and con-
mains controversial. cluded that when there was no direct invasion of the spleen or
splenic hilar lymph node metastasis under direct vision, sple-
In addition to the D1, D2 and D3 lymph node dissection, dif- nectomy with the clearance of the splenic hilum, splenic ar-
ferent degrees of subclasses have been suggested such as tery, and lymph nodes was not necessary [16]. In 2014, a study
D1 lymph node dissection with an additional seventh group showed that dissection of the superior mesenteric vein lymph

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Surgical treatment of advanced gastric cancer
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REVIEW ARTICLES

node (14v) combined with D2 gastrectomy improved progno- open distal gastrectomy, and D2 lymph node dissection [27].
sis in patients with stage III and IV distal gastric cancer, but The initial large multicenter retrospective cohort analysis was
this finding requires further verification with future controlled performed for stage T2–T4a gastric cancer with or without
clinical studies [17]. lymph node metastasis or distant metastasis [27]. The find-
ings showed that laparoscopy was safe and effective [27].
Therefore, based on the above results, D2 lymph node dissec- As to whether D2 radical surgery increased the risk of postop-
tion is recommended as a standard procedure in oncological erative complications, the CLASS team study showed that age
surgery guidelines for the treatment of advanced gastric can- ³65 years (OR=1.72; P <0.05), accompanied by multiple com-
cer, including guidelines from the Medical Oncology Society of plications (OR=2.76; P<0.05) increased the risk of postopera-
Japan, South Korea, and Europe. The National Comprehensive tive complications after laparoscopic D2 radical gastrectomy
Cancer Network (NCCN) in the US also recommends D1 or mod- for gastric cancer [27]. However, according to the number of
ified D2 lymph node dissection for advanced gastric cancer [18]. complications, the study concluded that there was no statis-
tical correlation between patient age ³65 years and postoper-
ative complications [27]. A meta-analysis also showed a lap-
Laparoscopic Surgery for Advanced Gastric aroscopic approach for D2 total gastrectomy did not increase
Cancer patient morbidity [28].

Laparoscopic surgery for the treatment of early gastric can- However, global clinical studies have mainly included lapa-
cer is performed routinely worldwide and is recommended as roscopic distal gastrectomy and total gastrectomy, and there
a standard treatment in Japan and South Korea. The results have been no randomized studies that have compared lapa-
from two prospective trials (KLASS 01 and JCOG 0703) have roscopic radical gastrectomy for distal gastric cancer, and lap-
further confirmed the safety and feasibility of laparoscopic sur- aroscopic-assisted total gastrectomy as an alternative to tra-
gery for early gastric cancer [19,20]. There have been further ditional surgical methods. The main reasons for the lack of
studies that have supported the use of laparoscopy-assisted studies are that the technique of total laparoscopic gastrec-
gastrectomy for advanced gastric cancer, but this type of sur- tomy remains to be standardized, even by experienced sur-
gery requires training and experience [21–23]. However, the use geons and is a complex procedure, and also there is no stan-
of minimally invasive techniques remains controversial for the dardized method for performing the anastomosis between the
treatment of advanced-stage tumors, mainly because of con- esophagus and the jejunum. Therefore, the use of laparoscopic
cerns about the adequacy of surgical resection and the ability methods for total gastrectomy for early gastric cancer and ad-
to adequately perform surgical lymph node dissection [24]. vanced gastric cancer remain rarely performed.

A multicenter randomized controlled trial of stage II/III gastric

cancer (JLSSG0901) from the Japanese Laparoscopic Surgery Resection of the Lesser Omentum for
Study Group (JLSGG) was conducted in patients with ad- Advanced Gastric Cancer
vanced gastric cancer [10]. To evaluate whether laparoscopic
surgery can achieve the same results as open surgery, the There remains controversy about whether or not to perform
main endpoint of JLSSG0901 was relapse-free survival, pend- omental resection during radical gastrectomy for gastric cancer.
ing the disclosure of level I evidence [10]. A phase III clinical The Japan gastric Cancer Association have recommended that
trial (KLASS-02) from the Korea Laparoscopic Gastrointestinal only patients with gastric cancer with serous infiltration should
Surgery Group was conducted to evaluate the long-term efficacy be treated with omental resection [29]. In 2012, Fujita et al. re-
of laparoscopic D2 lymph node dissection in the treatment of ported the findings from a randomized controlled trial of the
advanced gastric cancer (cT2–T4a/cN0–N1) [25]. There was long-term outcome of omentectomy during standard total or
no significant difference in the short-term curative effect be- distal D2 gastrectomy [30]. There was no significant difference
tween the two methods, and showed that the average learn- in the 3-year cumulative survival rate between the omental re-
ing curve of laparoscopic gastric cancer surgery was 42 cases, section group and the non-resection group (85.6% vs. 79.6%;
which provided a useful reference [25]. A single-center study P=0.443) [30]. Subgroup analysis showed that the 3-year cumu-
showed that the combination of laparoscopic gastrectomy and lative survival rate was 69.8% in the omental resection group,
the Enhanced Recovery After Surgery (ERAS) protocol in pa- and 50.2% in the non-resection group (P=0.043), and the inci-
tients with gastric cancer was feasible and resulted in good dence of abdominal metastasis in patients without omentec-
clinical outcome [26]. The Chinese Laparoscopic Gastrointestinal tomy was significantly higher than that in patients who un-
Surgery Research Group (CLASS) conducted a randomized con- derwent omentectomy (13.2% vs. 8.7%) [30]. However, JCOG
trolled trial (LASS-01) of laparoscopic gastrectomy for gastric followed this study with a large multicenter randomized con-
cancer in China and compared treatment with laparoscopy, trolled trial (JCOG1001) that assessed the long-term benefits

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 Tan Z.:
REVIEW ARTICLES Surgical treatment of advanced gastric cancer
© Med Sci Monit, 2019; 25: 3537-3541

of D2 lymph node dissection combined with omental resec- Conclusions

tion in patients with T3–T4 advanced gastric cancer [31].
Compared with the omental preservation group, the operation Currently, patients with advanced gastric cancer are still mainly
time and intraoperative blood loss were significantly increased treated by surgery, combined with intraperitoneal chemother-
in the omental resection group, and the 3-year survival rates apy and hyperthermic perfusion therapy, to improve surgical
were 83.3% and 86.0%, respectively [31]. The findings from treatment. Because T and N staging before and during surgery
this study indicated that patients with stage T3 or T4 gastric is not very reliable, D2 lymphadenectomy is recommended.
cancer did not benefit from routine omental resection [31]. With the advent of individualized and personalized medicine,
Yamamura et al. found that if gastric cancer micrometastases continued improvements in the treatment of advanced gastric
involved the omental sac, as confirmed by polymerase chain cancer require support from randomized clinical trials, which
reaction (PCR), there was also likely to be tumor spread to the are also needed to provide evidence to support D2 lymph
abdominal cavity, and omental resection was very unlikely to node dissection following neoadjuvant chemotherapy. Most
improve patient survival [32]. of the studies on the role of total laparoscopic gastrectomy
and omental resection are have included small study popu-
Currently, surgeons in Japan usually perform omental resection lations and adequately powered controlled prospective stud-
according to the recommendations from the Japanese guidelines ies are still required to reduce the limitations of selection bias
and includes resection of the transverse mesocolon and pancre- and heterogeneity. Continued studies are required to deter-
atic capsule (narrow omental sac resection). The advantage of mine the optimal approaches for the surgical treatment of pa-
omental sac resection during radical gastrectomy is the possible tients with advanced gastric cancer.
prevention of peritoneal dissemination, metastasis, and tumor
recurrence. However, omental resection increases the surgical Conflict of interest
difficulty and the operation time, and there is a risk of damag-
ing mesenteric vessels and the pancreas resulting in bleeding None.
and pancreatic leak. Open gastrectomy also prolongs the op-
eration time and requires the use of a general anesthetic with
an increase in surgical and anesthetic complications.

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