Content uploaded by Shun Zhang
Author content
All content in this area was uploaded by Shun Zhang on Jun 04, 2020
Content may be subject to copyright.
Available via license: CC BY-NC 4.0
Content may be subject to copyright.
World Journal of
Gastrointestinal Oncology
World J Gastrointest Oncol 2019 August 15; 11(8): 567-651
ISSN 1948-5204 (online)
Published by Baishideng Publishing Group Inc
W J G O World Journal of
Gastrointestinal
Oncology
Contents Monthly Volume 11 Number 8 August 15, 2019
REVIEW
567 Current surgical treatment of esophagogastric junction adenocarcinoma
Zhang S, Orita H, Fukunaga T
MINIREVIEWS
579 Hypofractionated particle beam therapy for hepatocellular carcinoma-a brief review of clinical effectiveness
Hsu CY, Wang CW, Cheng AL, Kuo SH
ORIGINAL ARTICLE
Basic Study
589 SFRP4 expression correlates with epithelial mesenchymal transition-linked genes and poor overall survival
in colon cancer patients
Nfonsam LE, Jandova J, Jecius HC, Omesiete PN, Nfonsam VN
599 KMT2D deficiency enhances the anti-cancer activity of L48H37 in pancreatic ductal adenocarcinoma
Li SS, Jiang WL, Xiao WQ, Li K, Zhang YF, Guo XY, Dai YQ, Zhao QY, Jiang MJ, Lu ZJ, Wan R
622 shRNA-interfering LSD1 inhibits proliferation and invasion of gastric cancer cells via VEGF-C/PI3K/AKT
signaling pathway
Pan HM, Lang WY, Yao LJ, Wang Y, Li XL
Retrospective Study
634 Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant
treatment of localized gastric or gastroesophageal junction cancer: A retrospective study
Basso V, Orry D, Fraisse J, Vincent J, Hennequin A, Bengrine L, Ghiringhelli F
642 Retrospective evaluation of lymphatic and blood vessel invasion and Borrmann types in advanced proximal
gastric cancer
Gao S, Cao GH, Ding P, Zhao YY, Deng P, Hou B, Li K, Liu XF
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
I
Contents World Journal of Gastrointestinal Oncology
Volume 11 Number 8 August 15, 2019
ABOUT COVER Editorial Board Member of World Journal of Gastrointestinal Oncology, Florin
Burada, MD, PhD, Associate Professor, Department of Medical Genetics
and Human Genomics Laboratory, Research Center of Gastroenterology
and Hepatology, University of Medicine and Pharmacy of Craiova, Craiova
200349, Romania
AIMS AND SCOPE World Journal of Gastrointestinal Oncology (World J Gastrointest Oncol, WJGO,
online ISSN 1948-5204, DOI: 10.4251) is a peer-reviewed open access
academic journal that aims to guide clinical practice and improve diagnostic
and therapeutic skills of clinicians.
The WJGO covers topics concerning carcinogenesis, tumorigenesis,
metastasis, diagnosis, prevention, prognosis, clinical manifestations,
nutritional support, etc. The current columns of WJGO include editorial,
frontier, field of vision, review, original articles, case report.
We encourage authors to submit their manuscripts to WJGO. We will give
priority to manuscripts that are supported by major national and
international foundations and those that are of great clinical significance.
INDEXING/ABSTRACTING The WJGO is now indexed in Science Citation Index Expanded (also known as
SciSearch®), PubMed, and PubMed Central. The 2019 edition of Journal Citation
Reports® cites the 2018 impact factor for WJGO as 2.758 (5-year impact factor: 3.220),
ranking WJGO as 52 among 84 journals in gastroenterology and hepatology (quartile in
category Q3), and 131 among 229 journals in oncology (quartile in category Q3).
RESPONSIBLE EDITORS FOR
THIS ISSUE
Responsible Electronic Editor: Yun-Xiaojian Wu
Proofing Production Department Director: Xiang Li
NAME OF JOURNAL
World Journal of Gastrointestinal Oncology
ISSN
ISSN 1948-5204 (online)
LAUNCH DATE
February 15, 2009
FREQUENCY
Monthly
EDITORS-IN-CHIEF
Monjur Ahmed, Rosa M Jimenez Rodriguez, Pashtoon Murtaza Kasi
EDITORIAL BOARD MEMBERS
https://www.wjgnet.com/1948-5204/editorialboard.htm
EDITORIAL OFFICE
Jin-Lei Wang, Director
PUBLICATION DATE
August 15, 2019
COPYRIGHT
© 2019 Baishideng Publishing Group Inc
INSTRUCTIONS TO AUTHORS
https://www.wjgnet.com/bpg/gerinfo/204
GUIDELINES FOR ETHICS DOCUMENTS
https://www.wjgnet.com/bpg/GerInfo/287
GUIDELINES FOR NON-NATIVE SPEAKERS OF ENGLISH
https://www.wjgnet.com/bpg/gerinfo/240
PUBLICATION MISCONDUCT
https://www.wjgnet.com/bpg/gerinfo/208
ARTICLE PROCESSING CHARGE
https://www.wjgnet.com/bpg/gerinfo/242
STEPS FOR SUBMITTING MANUSCRIPTS
https://www.wjgnet.com/bpg/GerInfo/239
ONLINE SUBMISSION
https://www.f6publishing.com
© 2019 Baishideng Publishing Group Inc. All rights reserved. 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
E-mail: bpgoffice@wjgnet.com https://www.wjgnet.com
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
II
W J G O World Journal of
Gastrointestinal
Oncology
Submit a Manuscript: https://www.f6publishing.com World J Gastrointest Oncol 2019 August 15; 11(8): 567-578
DOI: 10.4251/wjgo.v11.i8.567 ISSN 1948-5204 (online)
REVIEW
Current surgical treatment of esophagogastric junction
adenocarcinoma
Shun Zhang, Hajime Orita, Tetsu Fukunaga
ORCID number: Shun Zhang
(0000-0002-3493-1247); Hajime Orita
(0000-0002-8263-7069); Tetsu
Fukunaga (0000-0003-4802-8945).
Author contributions: All authors
equally contributed to this paper
with conception and design of the
study, literature review and
analysis, drafting and critical
revision and editing, and final
approval of the final version.
Supported by Japan China
Sasakawa Medical Fellowship.
Conflict-of-interest statement: No
potential conflicts of interest.
Open-Access: This article is an
open-access article which was
selected by an in-house editor and
fully peer-reviewed by external
reviewers. It is distributed in
accordance with the Creative
Commons Attribution Non
Commercial (CC BY-NC 4.0)
license, which permits others to
distribute, remix, adapt, build
upon this work non-commercially,
and license their derivative works
on different terms, provided the
original work is properly cited and
the use is non-commercial. See:
http://creativecommons.org/licen
ses/by-nc/4.0/
Manuscript source: Invited
manuscript
Received: February 26, 2019
Peer-review started: February 27,
2019
First decision: June 4, 2019
Revised: June 26, 2019
Accepted: July 16, 2019
Shun Zhang, Department of Gastroenterology Surgery, Shanghai East Hospital (East Hospital
Affiliated to Tongji University), Shanghai 200120, China
Shun Zhang, Hajime Orita, Tetsu Fukunaga, Department of Gastroenterology and Minimally
Invasive Surgery, Juntendo University Hospital, Tokyo 113-8431, Japan
Corresponding author: Tetsu Fukunaga, MD, PhD, Professor, Department of Gastroenterology
and Minimally Invasive Surgery, Juntendo University Hospital, 3-1-3 Hongo, Bunkyo-ku,
Tokyo 113-8431, Japan. t2fukunaga@juntendo.ac.jp
Telephone: +81-0358021556
Fax: +81-0358021557
Abstract
The incidence of esophagogastric junction (EGJ) adenocarcinoma has shown an
upward trend over the past several decades worldwide. In this article, we review
previous studies and aimed to provide an update on the factors related to the
surgical treatment of EGJ adenocarcinoma. The Siewert classification has
implications for lymph node spread and is the most commonly used
classification. Different types of EGJ cancer have different incidences of
mediastinal and abdominal lymph node metastases, and different surgical
approaches have unique advantages and disadvantages. Minimally invasive
surgeries have been increasingly applied in clinical practice and show
comparable oncologic outcomes. Endoscopic resection may be a good therapy for
early EGJ cancer. Additionally, there is still a great need for well-designed, large
RCTs to forward our knowledge on the surgical treatment of EGJ cancer.
Key words: Esophagogastric junction cancer; Surgery; Lymph nodes; Siewert
classification
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Core tip: This is a review article on the current strategies for the surgical management of
esophagogastric junction (EGJ) cancer. This article covers the different aspects related
with the surgical treatment of EGJ cancer and provides comparison between different
modalities discussed.
Citation: Zhang S, Orita H, Fukunaga T. Current surgical treatment of esophagogastric
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
567
Article in press: July 16, 2019
Published online: August 15, 2019
P-Reviewer: Ouaissi M, Bintintan
VV, Karamouzis MV
S-Editor: Dou Y
L-Editor: A
E-Editor: Qi LL
junction adenocarcinoma. World J Gastrointest Oncol 2019; 11(8): 567-578
URL: https://www.wjgnet.com/1948-5204/full/v11/i8/567.htm
DOI: https://dx.doi.org/10.4251/wjgo.v11.i8.567
INTRODUCTION
Gastrointestinal (GI) cancers are aggressive diseases, accounting for more than one-
fourth of the newly diagnosed cancers worldwide (more than 4 million new cases per
year). Among the GI cancers, the esophagogastric junction, or esophagogastric
junction (EGJ), is a special anatomical site with a remarkably high risk of
adenocarcinoma. The incidence of EGJ adenocarcinoma has shown an upward trend
over the past several decades both in the West and East[1-3]. Due to its location between
the esophagus and stomach, some investigators regard EGJ cancer as an entity
separate from esophageal and gastric cancers. There has been much debate as to the
pathogeny, diagnosis, classification, and optimal therapy for EGJ cancer, and the
debate continues[4].
The definition of the location of the EGJ by endoscopy or upper GI radiography
and its appearance on histopathology are different. The EGJ or Z-line is theoretically
defined as the histological transition from the squamocolumnar junction between the
esophagus and stomach. Actually, this transition does not occur exactly in the
anatomical transition between the esophagus and stomach[5]. In clinical practice, the
EGJ is defined by the proximal margin of the longitudinal folds of the stomach
transformed by the tubular esophagus.
In this article, we review previous studies and aimed to provide an update on the
different aspects related to the surgical treatment of EGJ cancer.
EGJ CANCER CLASSIFICATION
To improve the diagnosis and to allow the comparison of treatment results, Siewert
and coworkers developed a system that separated EGJ tumors into three subtypes
based purely on the macroscopic location of the tumor epicenter[6] (Table 1). Type I
tumors are with an epicenter 1-5 cm above the EGJ; type II: Those within 1 cm above
and 2 cm below the EGJ; and type III: Those 2-5 cm below the EGJ. The Siewert
classification has practical implications for lymph node spread and is the most
commonly used classification. The aim of the Siewert classification is not only for
prognosis but also for therapeutic decision-making.
In the current (8th) edition of the TNM classification of malignant tumors, EGJ
adenocarcinoma was redefined. Tumor epicenters within 2 cm proximal or distal to
the EGJ are staged as esophageal adenocarcinomas, and those whose epicenters are
more than 2 cm distal from the EGJ are staged as gastric cancer. The TNM
classification also indicated that using the genetic signature of EGJ cancers may
identify the cell of origin for cancer staging more accurately than the gross location of
the tumor[7,8]. Cancer genetics will be included in the next (9th) edition staging of EGJ
cancers.
Japanese gastric cancer treatment guidelines define EGJ cancer as a tumor (≤ 4 cm
diameter) with an epicenter located within 2 cm of the EGJ, whether adenocarcinoma
or squamous cell carcinoma. The Japanese classification was based on retrospective
data from 3177 patients operated on between 2001 and 2010 from 273 institutions[9].
Siewert type III and part of Siewert type I tumors are not covered by the Japanese
classification.
THE IMPORTANCE OF THE PRECISE LOCALIZATION OF
TUMORS
EGJ cancers have unique characteristics that make the risk of lymph node (LN)
metastasis high, and both the mediastinal and abdominal fields are the main
lymphatic drainage areas. The surgical approach and type of lymphadenectomy have
a close relationship with LN metastasis. The pattern of LN spread is also closely
related to the location of the EGJ tumor. To develop the optimal treatment for EGJ
cancers, it is important to identify the exact tumor location and estimate the exact
length and depth of esophageal and gastric invasion preoperatively.
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
568
Table 1 Different classification of esophagogastric junction cancer
System Classification Description
Siewert classification Type I 1-5 cm above the EGJ
Type II Within 1 cm above and 2 cm below the EGJ
Type III 2-5 cm below the EGJ
AJCC/UICC TNM Esophageal adenocarcinomas Within 2 cm proximal or distal to the EGJ
Gastric cancer More than 2 cm distal from the EGJ
Japanese classification - A tumor (≤ 4 cm diameter) with an epicenter
locating within 2 cm of the EGJ, whether
adenocarcinoma or squamous cell carcinoma
EGJ: Esophagogastric junction; AJCC: American Joint Committee on Cancer; UICC: Union for International Cancer Control.
The precise localization of tumors can be frequently difficult to assess through
endoscopic ultrasound (EUS) and computed tomography (CT), which are thought to
be the best techniques currently available. This is particularly problematic for Siewert
II type cancer. EUS precisely localizes tumors only 66% of the time, and CT precisely
localizes tumors 57% of the time, compared to final operative pathology[10].
LYMPH NODE METASTASES ACCORDING TO THE
SIEWERT CLASSIFICATION
EGJ cancers have unique characteristics, and lymphatic drainage occurs in both the
mediastinal and abdominal areas. Adequate LN lymphadenectomy is an important
key to oncologically successful surgical resection. The incidence of LN metastases
increases with the depth of tumor infiltration, but LN location depends on the tumor
location. Siewert’s group reported the incidence of lymph node metastasis based on
1602 consecutive surgical patients[11]. Type II and type III cancers showed a higher risk
of LN metastases. The incidence of metastasis was 51.9%, 65.2%, and 77.8% for type I,
type II, and type III, respectively. Studies from Japan report that the incidence of
metastasis was 64.1% and 75% for type II and III, respectively[12]. The data were based
on 126 patients who underwent curative resection.
LN METASTASES IN TYPE I EGJ CANCER
Type I EGJ cancers metastasize to lower mediastinal LNs, and 15% metastasize to
upper mediastinal LNs. Paracardial regions and lower posterior mediastinal LNs are
the most frequently observed locations in type I cancers[11]. More recent studies from
Japan yielded similar results. LNs, including nos. 1, 2, 3a, and 7, had a frequent
incidence of metastasis[13], while other LNs were rarely involved. Therefore, total
gastrectomy for type I cancer is not routine due to the extremely rare risk of LN
metastases in the lower perigastric LNs. A surgical approach allowing both upper
perigastric and mediastinal lymphadenectomy would be suitable for type I cancer.
LN METASTASES IN TYPE II EGJ CANCER
Most studies focus on Siewert type II cancer, since it is considered the true EGJ tumor,
and the characteristics of metastases to mediastinal LNs remain debatable. The extent
of lymph node dissection determines the surgical field and the type of surgery. In
particular, it has an important influence on the topic of the transabdominal approach
due to the potential risk of leaving positive nodes in the mediastinal region. Twelve
percent of LN metastases involve lower mediastinal regions among surgical patients
reported by Siewert’s group. They also indicated that as the location of the tumor
approaches the gastric side, the incidence of mediastinal LN metastases gradually
decreases, while the incidence of abdominal LN metastases increases[11].
Many other studies have indicated that the location of mediastinal LN metastases is
closely related to the distance from the EGJ to the tumor. A Japanese multicenter
study retrospectively analyzed 315 pT2-4 Siewert II patients who received R0 or R1
resection. The results showed that the incidence of metastasis or recurrence was 4%,
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
569
7%, and 11% in the upper, middle, and lower mediastinal LNs, respectively. Among
315 patients in the study by Kurokawa et al[14], 176 underwent LN dissection in the
lower mediastinal region, and the metastasis rate in the lower mediastinal nodes was
17.6%. In 139 other patients who did not undergo dissection, the researchers described
a long follow-up period. The recurrence rate among these 139 patients was 3.6%.
Therefore, the researchers combined metastasis with recurrence to determine the final
overall rate of metastasis or recurrence, which was 11.4%. We should recognize that
recurrence does not always reflect metastasis at the time of surgery. This point was
the limitation of their study. It also revealed that the length of esophageal invasion
correlated with the number and location of mediastinal LN metastases. The incidence
of metastasis was much higher when the length of esophageal invasion was > 3 cm for
the upper or middle mediastinal nodes and > 2 cm for the lower mediastinal nodes[14].
The authors indicated that based on this result, if esophageal invasion of > 3 cm is
noted, the upper and middle mediastinal LNs should be harvested. A systematic
review reported that the frequency of LN metastasis in the lower mediastinal stations
ranged from 7.5 to 23.8%, whereas patients with upper mediastinal node involvement
had a frequency of LN metastasis below 4%[15].
Several retrospective studies of abdominal LN metastasis in type II cancer were
performed in Japan[12,13,16-19]. Fujitani et al[16], Yoshikawa et al[13] and Yamashita et al[17] all
reported that the incidence of metastasis was especially low in the lower perigastric
LNs (nos. 4d-6), whereas it was higher in the upper half of perigastric LNs (nos. 1, 2,
and 3) and the second-tier LNs (nos. 7, 9, and 11). LN nos. 1 and 3 had the highest
metastasis incidence (up to 39.1%)[12], and that in the celiac axis around the splenic
artery and the splenic hilum was less than 10%[12,18]. However, if the distance from the
EGJ to the distal end of the tumor was more than 5 cm, the LN metastasis incidence at
the greater curvature (nos. 4sa, 4sb, 4d, and 6) or antrum was as high as 20%[19]. These
results may indicate that harvesting the perigastric nodes of the lower half of the
stomach is not beneficial if the distance from the EGJ to the anal edge of the tumor is
greater than 5 cm.
Taken together, these results show that type II cancers mainly metastasize to the
abdominal LNs around the stomach. The lower mediastinal compartment is the most
common site of mediastinal LN metastases. Esophagectomy with proximal
gastrectomy might be enough in type II cancer; however, it is better that the lower
mediastinal compartment be routinely sampled during the operation. An accurate
preoperative evaluation of the length of esophageal invasion is therefore essential, as
it can be used as a reference point for mediastinal LN metastases.
LN METASTASES IN TYPE III EGJ CANCER
Regarding type III cancer, perigastric LNs are the most common metastasis areas,
with approximately 2% to 18% of them having simultaneous positive mediastinal
nodes[20-23]. Among the perigastric LNs, nos. 4sa, 4sb, 4d, 8a, 9, and 11p show a high
risk of metastasis, whereas LN nos. 1, 2, 3, and 7 do not[20,24]. Although the incidence of
LN no. 10 metastasis ranges from 10%-20%, there is no survival benefit associated
with adding a splenectomy to a D2 lymphadenectomy[25,26]. It is recommended that the
splenectomy be performed only to obtain R0 resection[27,28]. Notably, a splenic hilar
lymphadenectomy is technically difficult and quite sophisticated due to the deeply
located operative field, limited space, and tortuous and variant vessels at this site.
With the accumulation of experience, new technological emergences and new surgical
energy instruments, this procedure has gradually become possible.
Taken together, these results indicate that total gastrectomy should be conducted
for type III cancers to obtain enough LNs, but splenectomy is not routine only to
obtain R0 resection.
TUMOR SIZE AND INVASION WITH LN METASTASIS
The depth of tumor invasion is another factor that is significantly correlated with the
presence of distal positive nodes[29], with an incidence of ≥ 60% in T2 and ≥ 85% in T3-
4 patients[20,21]. It was also reported that tumor size is a predictor of LN metastasis,
especially in large tumors (> 4 cm)[30].
LYMPHADENECTOMY AND PROGNOSIS
LN metastasis is also an indicator of prognosis. The highest risk factor is the number
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
570
of metastatic LNs ≥ 7[15,31]. Locoregional LN involvement is associated with improved
survival compared with para-aortal or other distant LNs[15]. In a systematic review
including 2252 type II cancer patients, ≥ 7 metastatic LNs (N3) indicated much worse
survival (2.0%-17.4%) compared to no LN metastasis (up to 82.7%)[15]. Whether a more
extensive lymphadenectomy in EGJ cancer is correlated with survival benefits has not
been determined. Extended dissection might improve the prognosis, but the
morbidity and mortality rates might also increase. In particular, some studies from the
West have shown no superior survival rates compared with the East when using a
more extended lymphadenectomy[31-34]. A multicenter retrospective study from the
United States indicated that the number of LNs harvested was an independent
predictor for survival after surgery. The authors concluded that a minimum of 23
regional LNs harvested can offer a survival benefit[35]. A cohort study of 262 pN0 type
II patients from China also confirmed this conclusion. The researchers indicated that
more than 15 LNs were recommended for patients undergoing curative resection[36].
Whether a more extensive lymphadenectomy in EGJ cancer can provide more
survival benefit was recently challenged. A Dutch study found no benefit from an
extended lymphadenectomy for type II disease[37]. A study from the United Kingdom
(n = 606)[38] and another recent retrospective cohort study from Denmark (n = 510)[31]
also showed no significant difference in survival between the extended and the less
extended lymphadenectomy.
Therefore, although LN metastasis puts a patient at high risk and is considered an
indicator of a poor prognosis, existing evidence does not support the benefits of an
extensive lymphadenectomy. Moderately extensive lymph node removal may be
enough to maximize the outcomes after EGJ cancer surgery.
PROXIMAL RESECTION MARGIN
The definition of R0 resection for EGJ is important. Feith et al[11] retrospectively
analyzed 1602 patients and found that the 5-year survival rate was 43.2% for a
negative margin versus 11% for a positive margin. However, the optimal extent of
esophagus resection required for the prevention of recurrence and longer survival
remains controversial[18,39-42]. Ito et al[43] advocated the proximal gross margin length of
at least 6 cm in patients with Siewert type II/III EGJ cancers, while Mariette et al[39]
advocated that 8 cm is necessary to prevent local recurrence.
A longer proximal margin length can ensure a negative margin, but it can also
increase the operation difficulty. An increasing number of studies have indicated that
a shorter proximal resection length may prove to be an adequate oncologic margin.
Barbour et al[40] reported that 5 cm of a grossly normal in vivo (approximately 3.8 cm ex
vivo) proximal esophagus was associated with improved survival for patients (≥ T2
and ≤ 6 positive lymph nodes) with Siewert types I/II/III. There were 58 patients with
more than 6 positive LNs. However, both univariate and multivariable analyses
showed that the proximal margin carried no prognostic significance for these patients.
Mine et al[18] reported another study of an even shorter proximal margin in Siewert
type II and III patients who received a transhiatal (TH) total gastrectomy. They
indicated improved survival with a proximal resection margin of 3.0 cm in vivo
(approximately 2.0 cm ex vivo)[18]. Feng et al[42] found that the proximal margin length
had no relationship with the survival of patients with Siewert type II/III EGJ cancers.
They concluded that a negative proximal margin may be sufficient during the surgical
resection of Siewert type II/III tumors[42]. A similar result was reported from the
United States Gastric Cancer Collaborative[44]. The authors found that the proximal
margin length was not associated with local recurrence or overall survival. They
suggested that achieving a specific proximal margin distance should be abandoned.
In conclusion, there is a trend that a shorter proximal resection margin is being
adopted in clinical practice due to similar oncology outcomes. Surgery is much easier
if the distal esophagus can be dissected through a transabdominal approach rather
than a transthoracic approach in an attempt to pursue a longer proximal margin.
SURGERY CHOICE ACCORDING TO THE SIEWERT
CLASSIFICATION
The key factors to a successful oncologic surgery are as follows: curative R0 resection,
adequate LN dissection, and the minimization of surgical morbidity. An esophago-
gastrectomy with a moderate, adequate lymphadenectomy is still considered the
standard surgical strategy for EGJ cancer, although there are some differences
according to Siewert types.
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
571
Because type I cancers arise from the distal esophagus, most experts and guidelines
recommend that they be treated surgically as esophageal cancer, with an
esophagogastrectomy plus both mediastinal and upper perigastric LN resection. For
type II cancers, some individuals recommend an esophagectomy with a proximal
gastrectomy, which allows the dissection of both the abdominal and mediastinal LNs.
Others advocate for a total gastrectomy and extended lymph node dissection with a
TH approach into the posterior mediastinum[45]. For type III cancers, an
esophagogastrectomy includes a total gastrectomy plus a distal esophagectomy via
laparotomy, by which the diaphragm is opened. The final anastomosis site is in the
distal part of the thoracic cavity. GI anastomosis is commonly an esophago-
jejunostomy with a Roux-en-Y reconstruction[46]. However, there is still no consensus
as to which surgical approach is suitable for an esophagogastrectomy. To summarize,
there are three main approaches for EGJ cancer resection - all are based on the Siewert
classification (Table 2): (1) The right transthoracic (RT) approach (the 2-step Ivor-
Lewis approach or the 3-step McKeown approach); (2) The left transthoracic (LT)
approach; and (3) The TH approach. Every approach has potential advantages and
disadvantages.
The transthoracic approach is usually performed with a laparotomy plus a
thoracotomy and sometimes with a cervical incision, allowing exploration of the
entire mediastinum. The final anastomosis is performed in the intrathoracic area (Ivor
Lewis approach) or the cervical area (McKeown approach). The potential advantages
of the RT approach are as follows: (1) There is a sufficient distance of the proximal
resection margin even in advanced EGJ cancers with extensive esophageal invasion;
and (2) It allows the exposure to the entire mediastinum to harvest even the upper
mediastinal LN. This procedure may especially benefit advanced-stage patients with
long esophageal invasion. Due to the low rate of invaded upper mediastinal LNs, the
Ivor Lewis approach without upper mediastinal LN dissection is usually performed
in Western countries[47]. The LT consisting of the left thoracoabdominal (LTA)
approach and left thoracophrenolaparotomy is not commonly used, although it has
the following advantages: (1) A sufficient proximal margin can be ensured; (2) Body
position change is not needed during the operation; and (3) The surgical procedure
around the esophageal hiatus is easy to perform under direct visualization. TH
esophagectomy is usually performed through a laparotomy with a cervical incision,
without a thoracotomy. Surgical stress, particularly respiratory damage, is the main
disadvantage of a thoracotomy. The TH approach consisting of the TH surgical
operation from the abdomen to the lower mediastinum minimizes such disadvantages
due to the avoidance of a thoracotomy. Changes in body position are also not needed
during the TH operation.
TH is inappropriate for esophageal cancer due to limited periesophageal LN
harvesting. However, many studies on esophageal cancer have demonstrated no
significant survival advantage for more radical surgery[48], and TH can be used to treat
esophageal cancer, with similar OS and even less morbidity[49]. Regarding EGJ cancers,
few studies comparing TH and the transthoracic approach have been reported.
Two randomized controlled trials comparing transthoracic with TH eso-
phagectomy were performed in the West and East[50,51]. The Dutch phase III clinical
trial (n = 205) compared RT with TH in patients with type I or type II EGJ cancer. The
RT group did not achieve a survival benefit but instead exhibited higher
postoperative morbidity[50]. In a subgroup analysis, the 5-year OS rate was similar
between RT and TH for patients with type II cancer but higher following RT than TH
for patients with type I cancer[37]. The authors concluded that RT may be
recommended only for patients with type I tumors and not type II tumors. The
Japanese phase III trial (n = 67) compared oncologic outcomes between LTA and TH
in patients with type II or type III EGJ cancer. However, due to limited efficacious
resection, the trial was stopped at the first interim analysis[51]. After 10 years of follow-
up, the LTA achieved no benefits in OS or DFS and did not reduce the cancer
recurrence rate in LNs. However, the LTA was associated with higher morbidity and
mortality[52]. Based on these results, the researchers suggested that the LTA be avoided
as a surgical therapy for adenocarcinoma of the EGJ or the gastric cardia. In Japan, the
consensus is that Siewert type II and type III cancers should be treated by an
abdominal, TH approach with en bloc lower mediastinal dissection with a length of
esophageal invasion ≤ 3 cm.
A United Kingdom cohort study (n = 664) found no differences between TH and
transthoracic approaches regarding survival or tumor recurrence in patients with
esophageal or EGJ cancer[32]. Yan et al[53] conducted a systematic review of 2202
patients to compare the clinical outcomes between TH and open thoracic
esophagectomy in EGJ cancer. The TH group showed decreased hospitalization,
operation time, and blood loss, with less LN dissection. The complication and survival
rates were not different between these approaches. A subtype analysis showed no
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
572
Table 2 Different approach for esophagogastric junction cancer
Approach Surgical technique Procedure Disadvantage
RT Ivor Lewis Midline laparotomy Limited proximal margin
Requirement of body position change
Surgical stress is significant
Mckeown Right thoracotomy Increased risk for recurrent laryngeal
nerve injury
Midline laparotomy Surgical stress is significant
Left cervical
LT LTA Left thoracotomy extended to upper
midline laparotomy
No middle or upper thoracic
lymphadenectomy
Surgical stress is significant
Left thoracophrenolaparotomy Transdiaphragmatic thoracotomy No middle or upper thoracic
lymphadenectomy
Midline laparotomy Surgical stress is significant
TH - Midline laparotomy Limited proximal margin
Left cervical Surgical view of the lower
mediastinum is poor
No middle or upper thoracic
lymphadenectomy
TG - Midline laparotomy Limited proximal margin
No thoracic lymphadenectomy
RT: Right Transthoracic; LT: Left Transthoracic; TH: transhiatal; TG: Total Gastrectomy.
significant differences according to the Siewert type[53]. Omloo et al[37] compared the
transthoracic and TH approaches for esophagectomy and found that the TH approach
was associated with a lower morbidity; however, better medium-term survival with
transthoracic esophagectomy was observed in two subgroups: patients with type I
AEG and those with ≤ 8 metastatic nodes.
Taken together, existing evidence does not support one technique over the other
regarding oncological outcomes. Future large RCTs are still needed to examine these
techniques and their effects on long-term OS.
MINIMALLY INVASIVE SURGERIES FOR EGJ CANCER
Minimally invasive surgeries are the gold standard in many fields of surgery. The first
minimally invasive esophagectomy was described by Cuschieri et al[54] in 1993, and
after one year, Kitano et al[55] reported the first minimally invasive gastrectomy. Since
then, the techniques for gastric cancer have evolved from laparoscopic assisted to total
laparoscopic surgery, and the techniques for esophagectomy have also evolved from
hybrid approaches to an entirely minimally invasive manner. Both minimally invasive
surgeries show similar surgical and oncological outcomes compared with open
surgeries, especially in early-stage patients. Zhou et al[56] conducted a systematic
review of minimally invasive esophagectomy approaches for esophageal or EGJ
cancer. The review that included 1 RCT and 47 observational studies indicated that
minimally invasive procedures (n = 4509) have lower pulmonary complications
compared with open surgery (n = 6347). There were no differences in anastomotic
leak or gastric tip necrosis between the two groups[56]. However, in the minimally
invasive procedures group, the authors included not only total minimally invasive
procedures but also thoracoscopy-assisted or hybrid procedures.
For type I and II cancers, there are different minimally invasive techniques
according to transthoracic or TH approaches compared to open surgery. Usually, the
minimally invasive Ivor-Lewis technique is the main choice, although intrathoracic
anastomosis is sometimes difficult. The operation starts with a laparoscopy with a
proximal gastrectomy plus a lymphadenectomy. Then, the operation is followed by a
right thoracoscopy, including esophagus mobilization and a mediastinal
lymphadenectomy between the area from the carina to the azygos vein. The gastric
tube is pulled into the thorax through the hiatus to create an intrathoracic
anastomosis. The anastomosis methods include end-to-side anastomosis with a
manual or circular stapler (with or without an OrVil device)[57] and side-to-side
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
573
anastomosis with a linear stapler (with or without barbed sutures)[58].
The minimally invasive McKeown procedure commences with a right thoracoscopy
followed by esophagus dissection and a mediastinal lymphadenectomy, which are
similar to the previous description of the Ivor Lewis technique. Subsequently, the
patient’s position is changed to a supine position, and then a laparoscopic
gastrectomy with a lymphadenectomy is performed. The formation of the gastric tube
is also similar to that descried in the Ivor Lewis technique. After the laparoscopy, a
left cervical incision is made, and the divided esophagus is anastomosed with a
gastric tube manually using end-to-end anastomosis[59]. van Workum et al[60]
conducted a systematic review (n = 1681) to compare the totally minimally invasive
McKeown and Ivor Lewis technique used for esophageal and EGJ cancers. The Ivor
Lewis group showed decreased RLN trauma, hospitalization, and blood loss
compared to the McKeown group, while the anastomotic leakage rate was not
different[60]. It is noteworthy that the evidence is limited, and all included studies were
cohort studies with a moderate risk of bias. It is still uncertain which minimally
invasive technique is suitable. The Netherlands is now performing the first
randomized controlled trial containing 200 patients between minimally invasive
McKeown and Ivor Lewis approaches. This clinical trial is powered for finding
differences in morbidity, the severity of complications and quality of life[61]. The
minimally invasive TH procedure consists of a laparoscopy and a left cervical incision
followed by a gastrectomy plus a lymphadenectomy and TH dissection of the distal
esophagus through a laparoscopy. The gastric tube is created extracorporeally and
then pulled into the cervical area where the anastomosis is made[62].
For type III cancers, a laparoscopic gastrectomy is the main choice. A total D2
gastrectomy is performed, and the duodenum is divided using a liner stapler. The
diaphragm is opened, and the distal esophagus is mobilized. Only the distal
periesophageal LNs are resected, and then the vagal nerves and esophagus above the
cancer are transected. Because of the limited size of the hiatus, the OrVil® (Medtronic,
Inc., Minneapolis, MN, United States) is usually used to perform the end-side
esophagojejunostomy anastomosis[63].
In conclusion, there is still no agreement about the ideal type of minimally invasive
surgery, and existing evidence does not support that one technique is much better
than the other. Many anastomotic methods can be adopted, such as manual, circular
stapler, linear stapler, and even robot-assisted anastomoses. Large randomized
controlled trials are still needed to test which minimally invasive technique is most
suitable for EGJ cancer.
ENDOSCOPIC RESECTION FOR EARLY EGJ CANCER
Endoscopic resection (ER), including endoscopic mucosal resection (EMR) and
endoscopic submucosal dissection (ESD), is used to remove superficial neoplasms
from the GI tract[64,65]. However, the curative resection criteria, particularly for type II
cancers, differ between esophageal cancer and gastric cancer, since the rate of LN
metastasis is different[66].
The indications for ER in early EGJ adenocarcinoma are also under study. A
Japanese multicenter study retrospectively analyzed 458 esophageal or EGJ
adenocarcinoma patients who received surgical or ER treatment. Lymphovascular
involvement, a poorly differentiated tumor, and lesion size > 30 mm were
independent risk factors for metastasis. Mucosal and submucosal cancers with
invasion of less than 500 µm without the abovementioned risk factors may also be
suitable for ER[67].
Favorable oncological results were also reported in several studies. A systematic
review analyzed 359 early EGJ adenocarcinoma patients who received ESD treatment.
More than 20% of tumors were reported to have deep submucosal invasion (> 500
mm from the muscularis mucosa). The en bloc resection and complete resection rates
were 98.6% and 87%, respectively. Patients with curative resection showed no local
recurrence or distant metastases[68]. A Korean retrospective study demonstrated
similar 5-year OS rates between ESD and surgery (93.9% vs 97.3%, respectively, P =
0.37). Local recurrence and cancer-related deaths were not observed[69]. Recently, a
retrospective study from 13 centers in Japan reported the long-term outcomes of ER
for EGJ adenocarcinoma. The 5-year cumulative incidences of local recurrence were
13% for EMR and 0.5% for ESD. In this study, patients were classified into 2 groups
based on the risk of metastasis according to the histologic features. Patients at a low
risk for metastasis were defined as those with mucosal cancer without LVI and a
poorly differentiated component or those with a cancer with an SM depth ≤ 500 μm
without LVI, without a poorly differentiated component, and measuring ≤ 30 mm.
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
574
High-risk patients were defined as those with mucosal and SM EGJ (except for low-
risk criteria). According to the abovementioned risk factors for LN metastasis, there
were 277 patients in the low-risk group and 95 patients in the high-risk group. The 5-
year OS rates of the low-risk group, the high-risk group with additional treatment,
and the high-risk group without additional treatment were 93.9%, 77.7%, and 81.6%,
respectively. The authors concluded that patients with a low risk for LN metastasis
may obtain favorable long-term outcomes after ER treatment[70].
Therefore, ER may be a good therapy for early-stage (intramucosal) EGJ cancer. Not
all patients with early EGJ cancer can be treated with ER. The incidence of metastasis
should be understood, and a confirmation of the indication would maximize the
benefits of ER for early EGJ cancer. However, RCTs are needed to inform the benefits
and harms of ER therapy for early EGJ cancer.
CONCLUSION
The incidence of EGJ cancer is increasing. Tumor location is an important factor in
determining the optimal surgical therapy for EGJ. The Siewert classification has
implications for lymph node spread and is the most commonly used classification.
Different types of EGJ cancer have different incidences of mediastinal and abdominal
LN metastases, and different surgical approaches have unique advantages and
disadvantages. The length of the tumor and the depth of tumor invasion should also
be considered when deciding the proper surgical technique. An extensive
lymphadenectomy may not provide additional benefits. Minimally invasive surgeries
are increasingly applied in clinical practice and show comparable oncologic outcomes.
ER may be a good therapy for early EGJ cancer. Additionally, there is still a great need
for well-designed large RCTs to forward our knowledge in the surgical treatment of
EGJ cancer.
ACKNOWLEDGEMENTS
The authors thank Prof. Mike Gibson (Vanderbilt University School of Medicine,
United States) for his critical correction of the English language in the manuscript.
REFERENCES
1Imamura Y, Watanabe M, Toihata T, Takamatsu M, Kawachi H, Haraguchi I, Ogata Y, Yoshida N, Saeki
H, Oki E, Taguchi K, Yamamoto M, Morita M, Mine S, Hiki N, Baba H, Sano T. Recent Incidence Trend
of Surgically Resected Esophagogastric Junction Adenocarcinoma and Microsatellite Instability Status in
Japanese Patients. Digestion 2019; 99: 6-13 [PMID: 30554205 DOI: 10.1159/000494406]
2Steevens J, Botterweck AA, Dirx MJ, van den Brandt PA, Schouten LJ. Trends in incidence of
oesophageal and stomach cancer subtypes in Europe. Eur J Gastroenterol Hepatol 2010; 22: 669-678
[PMID: 19474750 DOI: 10.1097/MEG.0b013e32832ca091]
3Bollschweiler E, Wolfgarten E, Gutschow C, Hölscher AH. Demographic variations in the rising
incidence of esophageal adenocarcinoma in white males. Cancer 2001; 92: 549-555 [PMID: 11505399
DOI: 10.1002/1097-0142(20010801)92:3<549::aid-cncr1354>3.0.co;2-l]
4Kauppila JH, Lagergren J. The surgical management of esophago-gastric junctional cancer. Surg Oncol
2016; 25: 394-400 [PMID: 27916171 DOI: 10.1016/j.suronc.2016.09.004]
5Riddell RH. The genesis of Barrett esophagus: has a histologic transition from gastroesophageal reflux
disease-damaged epithelium to columnar metaplasia ever been seen in humans? Arch Pathol Lab Med
2005; 129: 164-169 [PMID: 15679412]
6Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg 1998;
85: 1457-1459 [PMID: 9823902 DOI: 10.1046/j.1365-2168.1998.00940.x]
7Hayakawa Y, Sethi N, Sepulveda AR, Bass AJ, Wang TC. Oesophageal adenocarcinoma and gastric
cancer: should we mind the gap? Nat Rev Cancer 2016; 16: 305-318 [PMID: 27112208 DOI:
10.1038/nrc.2016.24]
8Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric
adenocarcinoma. Nature 2014; 513: 202-209 [PMID: 25079317 DOI: 10.1038/nature13480]
9Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric
Cancer 2017; 20: 1-19 [PMID: 27342689 DOI: 10.1007/s10120-016-0622-4]
10 Parry K, Haverkamp L, Bruijnen RC, Siersema PD, Offerhaus GJ, Ruurda JP, van Hillegersberg R.
Staging of adenocarcinoma of the gastroesophageal junction. Eur J Surg Oncol 2016; 42: 400-406 [PMID:
26777127 DOI: 10.1016/j.ejso.2015.11.014]
11 Feith M, Stein HJ, Siewert JR. Adenocarcinoma of the esophagogastric junction: surgical therapy based
on 1602 consecutive resected patients. Surg Oncol Clin N Am 2006; 15: 751-764 [PMID: 17030271 DOI:
10.1016/j.soc.2006.07.015]
12 Goto H, Tokunaga M, Miki Y, Makuuchi R, Sugisawa N, Tanizawa Y, Bando E, Kawamura T, Niihara M,
Tsubosa Y, Terashima M. The optimal extent of lymph node dissection for adenocarcinoma of the
esophagogastric junction differs between Siewert type II and Siewert type III patients. Gastric Cancer
2014 [PMID: 24658651 DOI: 10.1007/s10120-014-0364-0]
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
575
13 Yoshikawa T, Takeuchi H, Hasegawa S, Nozaki I, Kishi K, Ito S, Ohi M, Mine S, Hara J, Matsuda T,
Hiki N, Kurokawa Y. Theoretical therapeutic impact of lymph node dissection on adenocarcinoma and
squamous cell carcinoma of the esophagogastric junction. Gastric Cancer 2016; 19: 143-149 [PMID:
25414051 DOI: 10.1007/s10120-014-0439-y]
14 Kurokawa Y, Hiki N, Yoshikawa T, Kishi K, Ito Y, Ohi M, Wada N, Takiguchi S, Mine S, Hasegawa S,
Matsuda T, Takeuchi H. Mediastinal lymph node metastasis and recurrence in adenocarcinoma of the
esophagogastric junction. Surgery 2015; 157: 551-555 [PMID: 25532434 DOI:
10.1016/j.surg.2014.08.099]
15 Okholm C, Svendsen LB, Achiam MP. Status and prognosis of lymph node metastasis in patients with
cardia cancer - a systematic review. Surg Oncol 2014; 23: 140-146 [PMID: 24953457 DOI: 10.1016/j.sur-
onc.2014.06.001]
16 Fujitani K, Miyashiro I, Mikata S, Tamura S, Imamura H, Hara J, Kurokawa Y, Fujita J, Nishikawa K,
Kimura Y, Takiguchi S, Mori M, Doki Y. Pattern of abdominal nodal spread and optimal abdominal
lymphadenectomy for advanced Siewert type II adenocarcinoma of the cardia: results of a multicenter
study. Gastric Cancer 2013; 16: 301-308 [PMID: 22895616 DOI: 10.1007/s10120-012-0183-0]
17 Yamashita H, Katai H, Morita S, Saka M, Taniguchi H, Fukagawa T. Optimal extent of lymph node
dissection for Siewert type II esophagogastric junction carcinoma. Ann Surg 2011; 254: 274-280 [PMID:
21772128 DOI: 10.1097/SLA.0b013e3182263911]
18 Mine S, Sano T, Hiki N, Yamada K, Kosuga T, Nunobe S, Yamaguchi T. Proximal margin length with
transhiatal gastrectomy for Siewert type II and III adenocarcinomas of the oesophagogastric junction. Br J
Surg 2013; 100: 1050-1054 [PMID: 23754647 DOI: 10.1002/bjs.9170]
19 Mine S, Kurokawa Y, Takeuchi H, Kishi K, Ito Y, Ohi M, Matsuda T, Hamakawa T, Hasegawa S,
Yoshikawa T, Hiki N. Distribution of involved abdominal lymph nodes is correlated with the distance
from the esophagogastric junction to the distal end of the tumor in Siewert type II tumors. Eur J Surg
Oncol 2015; 41: 1348-1353 [PMID: 26087995 DOI: 10.1016/j.ejso.2015.05.004]
20 Pedrazzani C, de Manzoni G, Marrelli D, Giacopuzzi S, Corso G, Minicozzi AM, Rampone B, Roviello
F. Lymph node involvement in advanced gastroesophageal junction adenocarcinoma. J Thorac Cardiovasc
Surg 2007; 134: 378-385 [PMID: 17662776 DOI: 10.1016/j.jtcvs.2007.03.034]
21 Meier I, Merkel S, Papadopoulos T, Sauer R, Hohenberger W, Brunner TB. Adenocarcinoma of the
esophagogastric junction: the pattern of metastatic lymph node dissemination as a rationale for elective
lymphatic target volume definition. Int J Radiat Oncol Biol Phys 2008; 70: 1408-1417 [PMID: 18374226
DOI: 10.1016/j.ijrobp.2007.08.053]
22 Mönig SP, Baldus SE, Zirbes TK, Collet PH, Schröder W, Schneider PM, Dienes HP, Hölscher AH.
Topographical distribution of lymph node metastasis in adenocarcinoma of the gastroesophageal junction.
Hepatogastroenterology 2002; 49: 419-422 [PMID: 11995464]
23 Kakeji Y, Yamamoto M, Ito S, Sugiyama M, Egashira A, Saeki H, Morita M, Sakaguchi Y, Toh Y,
Maehara Y. Lymph node metastasis from cancer of the esophagogastric junction, and determination of the
appropriate nodal dissection. Surg Today 2012; 42: 351-358 [PMID: 22245924 DOI:
10.1007/s00595-011-0114-4]
24 Hosokawa Y, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Kato Y, Daiko H, Nishimura M,
Katsumata K, Sugiyama Y, Kinoshita T. Clinicopathological features and prognostic factors of
adenocarcinoma of the esophagogastric junction according to Siewert classification: experiences at a single
institution in Japan. Ann Surg Oncol 2012; 19: 677-683 [PMID: 21822549 DOI:
10.1245/s10434-011-1983-x]
25 Hasegawa S, Yoshikawa T, Rino Y, Oshima T, Aoyama T, Hayashi T, Sato T, Yukawa N, Kameda Y,
Sasaki T, Ono H, Tsuchida K, Cho H, Kunisaki C, Masuda M, Tsuburaya A. Priority of lymph node
dissection for Siewert type II/III adenocarcinoma of the esophagogastric junction. Ann Surg Oncol 2013;
20: 4252-4259 [PMID: 23943020 DOI: 10.1245/s10434-013-3036-0]
26 Nunobe S, Ohyama S, Sonoo H, Hiki N, Fukunaga T, Seto Y, Yamaguchi T. Benefit of mediastinal and
para-aortic lymph-node dissection for advanced gastric cancer with esophageal invasion. J Surg Oncol
2008; 97: 392-395 [PMID: 18236414 DOI: 10.1002/jso.20987]
27 Mariette C, Piessen G, Briez N, Gronnier C, Triboulet JP. Oesophagogastric junction adenocarcinoma:
which therapeutic approach? Lancet Oncol 2011; 12: 296-305 [PMID: 21109491 DOI:
10.1016/S1470-2045(10)70125-X]
28 Lutz MP, Zalcberg JR, Ducreux M, Ajani JA, Allum W, Aust D, Bang YJ, Cascinu S, Hölscher A,
Jankowski J, Jansen EP, Kisslich R, Lordick F, Mariette C, Moehler M, Oyama T, Roth A, Rueschoff J,
Ruhstaller T, Seruca R, Stahl M, Sterzing F, van Cutsem E, van der Gaast A, van Lanschot J, Ychou M,
Otto F; First St Gallen EORTC Gastrointestinal Cancer Conference 2012 Expert Panel. Highlights of the
EORTC St. Gallen International Expert Consensus on the primary therapy of gastric, gastroesophageal and
oesophageal cancer - differential treatment strategies for subtypes of early gastroesophageal cancer. Eur J
Cancer 2012; 48: 2941-2953 [PMID: 22921186 DOI: 10.1016/j.ejca.2012.07.029]
29 Ielpo B, Pernaute AS, Elia S, Buonomo OC, Valladares LD, Aguirre EP, Petrella G, Garcia AT. Impact of
number and site of lymph node invasion on survival of adenocarcinoma of esophagogastric junction.
Interact Cardiovasc Thorac Surg 2010; 10: 704-708 [PMID: 20154347 DOI: 10.1510/icvts.2009.222778]
30 Shimada H, Suzuki T, Nakajima K, Hori S, Hayashi H, Takeda A, Arima M, Gunji Y, Koide Y, Ochiai T.
Lymph node metastasis with adenocarcinoma of the gastric cardia: clinicopathological analysis and
indication for D1 dissection. Int Surg 1999; 84: 13-17 [PMID: 10421011]
31 Okholm C, Fjederholt KT, Mortensen FV, Svendsen LB, Achiam MP. The optimal lymph node dissection
in patients with adenocarcinoma of the esophagogastric junction. Surg Oncol 2018; 27: 36-43 [PMID:
29549902 DOI: 10.1016/j.suronc.2017.11.004]
32 Davies AR, Sandhu H, Pillai A, Sinha P, Mattsson F, Forshaw MJ, Gossage JA, Lagergren J, Allum WH,
Mason RC. Surgical resection strategy and the influence of radicality on outcomes in oesophageal cancer.
Br J Surg 2014; 101: 511-517 [PMID: 24615656 DOI: 10.1002/bjs.9456]
33 Hulscher JB, Van Sandick JW, Offerhaus GJ, Tilanus HW, Obertop H, Van Lanschot JJ. Prospective
analysis of the diagnostic yield of extended en bloc resection for adenocarcinoma of the oesophagus or
gastric cardia. Br J Surg 2001; 88: 715-719 [PMID: 11350447 DOI: 10.1046/j.1365-2168.2001.01746.x]
34 Yamashita H, Seto Y, Sano T, Makuuchi H, Ando N, Sasako M; Japanese Gastric Cancer Association and
the Japan Esophageal Society. Results of a nation-wide retrospective study of lymphadenectomy for
esophagogastric junction carcinoma. Gastric Cancer 2017; 20: 69-83 [PMID: 27796514 DOI:
10.1007/s10120-016-0663-8]
35 Peyre CG, Hagen JA, DeMeester SR, Altorki NK, Ancona E, Griffin SM, Hölscher A, Lerut T, Law S,
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
576
Rice TW, Ruol A, van Lanschot JJ, Wong J, DeMeester TR. The number of lymph nodes removed predicts
survival in esophageal cancer: an international study on the impact of extent of surgical resection. Ann
Surg 2008; 248: 549-556 [PMID: 18936567 DOI: 10.1097/SLA.0b013e318188c474]
36 Wu XN, Liu CQ, Tian JY, Guo MF, Xu MQ. Prognostic significance of the number of lymph nodes
examined in node-negative Siewert type II esophagogastric junction adenocarcinoma. Int J Surg 2017; 41:
6-11 [PMID: 28323156 DOI: 10.1016/j.ijsu.2017.03.028]
37 Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van Dekken H, Ten Kate FJ, Obertop H,
Tilanus HW, van Lanschot JJ. Extended transthoracic resection compared with limited transhiatal resection
for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial. Ann Surg
2007; 246: 992-1000; discussion 1000-1 [PMID: 18043101 DOI: 10.1097/SLA.0b013e31815c4037]
38 Lagergren J, Mattsson F, Zylstra J, Chang F, Gossage J, Mason R, Lagergren P, Davies A. Extent of
Lymphadenectomy and Prognosis After Esophageal Cancer Surgery. JAMA Surg 2016; 151: 32-39
[PMID: 26331431 DOI: 10.1001/jamasurg.2015.2611]
39 Mariette C, Castel B, Balon JM, Van Seuningen I, Triboulet JP. Extent of oesophageal resection for
adenocarcinoma of the oesophagogastric junction. Eur J Surg Oncol 2003; 29: 588-593 [PMID: 12943624
DOI: 10.1016/S0748-7983(03)00109-4]
40 Barbour AP, Rizk NP, Gonen M, Tang L, Bains MS, Rusch VW, Coit DG, Brennan MF.
Adenocarcinoma of the gastroesophageal junction: influence of esophageal resection margin and operative
approach on outcome. Ann Surg 2007; 246: 1-8 [PMID: 17592282 DOI:
10.1097/01.sla.0000255563.65157.d2]
41 Mine S, Sano T. Authors' reply: Proximal margin length with transhiatal gastrectomy for Siewert type II
and III adenocarcinomas of the oesophagogastric junction (Br J Surg 2013; 100: 1050-1054). Br J Surg
2014; 101: 735-736 [PMID: 24723024 DOI: 10.1002/bjs.9504]
42 Feng F, Tian Y, Xu G, Liu S, Liu Z, Zheng G, Guo M, Lian X, Fan D, Zhang H. The length of proximal
margin does not influence the prognosis of Siewert type II/III adenocarcinoma of esophagogastric junction
after transhiatal curative gastrectomy. Springerplus 2016; 5: 588 [PMID: 27247885 DOI:
10.1186/s40064-016-2240-3]
43 Ito H, Clancy TE, Osteen RT, Swanson RS, Bueno R, Sugarbaker DJ, Ashley SW, Zinner MJ, Whang EE.
Adenocarcinoma of the gastric cardia: what is the optimal surgical approach? J Am Coll Surg 2004; 199:
880-886 [PMID: 15555971 DOI: 10.1016/j.jamcollsurg.2004.08.015]
44 Postlewait LM, Squires MH, Kooby DA, Poultsides GA, Weber SM, Bloomston M, Fields RC, Pawlik
TM, Votanopoulos KI, Schmidt CR, Ejaz A, Acher AW, Worhunsky DJ, Saunders N, Swords D, Jin LX,
Cho CS, Winslow ER, Cardona K, Staley CA, Maithel SK. The importance of the proximal resection
margin distance for proximal gastric adenocarcinoma: A multi-institutional study of the US Gastric Cancer
Collaborative. J Surg Oncol 2015; 112: 203-207 [PMID: 26272801 DOI: 10.1002/jso.23971]
45 Brown AM, Giugliano DN, Berger AC, Pucci MJ, Palazzo F. Surgical approaches to adenocarcinoma of
the gastroesophageal junction: the Siewert II conundrum. Langenbecks Arch Surg 2017; 402: 1153-1158
[PMID: 28803334 DOI: 10.1007/s00423-017-1610-9]
46 Di Leo A, Zanoni A. Siewert III adenocarcinoma: treatment update. Updates Surg 2017; 69: 319-325
[PMID: 28303519 DOI: 10.1007/s13304-017-0429-9]
47 Giacopuzzi S, Bencivenga M, Weindelmayer J, Verlato G, de Manzoni G. Western strategy for EGJ
carcinoma. Gastric Cancer 2017; 20: 60-68 [PMID: 28039533 DOI: 10.1007/s10120-016-0685-2]
48 Chang AC, Ji H, Birkmeyer NJ, Orringer MB, Birkmeyer JD. Outcomes after transhiatal and transthoracic
esophagectomy for cancer. Ann Thorac Surg 2008; 85: 424-429 [PMID: 18222237 DOI: 10.1016/j.athor-
acsur.2007.10.007]
49 Boshier PR, Anderson O, Hanna GB. Transthoracic versus transhiatal esophagectomy for the treatment of
esophagogastric cancer: a meta-analysis. Ann Surg 2011; 254: 894-906 [PMID: 21785341 DOI:
10.1097/SLA.0b013e3182263781]
50 Hulscher JB, van Sandick JW, de Boer AG, Wijnhoven BP, Tijssen JG, Fockens P, Stalmeier PF, ten
Kate FJ, van Dekken H, Obertop H, Tilanus HW, van Lanschot JJ. Extended transthoracic resection
compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 2002;
347: 1662-1669 [PMID: 12444180 DOI: 10.1056/NEJMoa022343]
51 Sasako M, Sano T, Yamamoto S, Sairenji M, Arai K, Kinoshita T, Nashimoto A, Hiratsuka M; Japan
Clinical Oncology Group (JCOG9502). Left thoracoabdominal approach versus abdominal-transhiatal
approach for gastric cancer of the cardia or subcardia: a randomised controlled trial. Lancet Oncol 2006; 7:
644-651 [PMID: 16887481 DOI: 10.1016/S1470-2045(06)70766-5]
52 Kurokawa Y, Sasako M, Sano T, Yoshikawa T, Iwasaki Y, Nashimoto A, Ito S, Kurita A, Mizusawa J,
Nakamura K; Japan Clinical Oncology Group (JCOG9502). Ten-year follow-up results of a randomized
clinical trial comparing left thoracoabdominal and abdominal transhiatal approaches to total gastrectomy
for adenocarcinoma of the oesophagogastric junction or gastric cardia. Br J Surg 2015; 102: 341-348
[PMID: 25605628 DOI: 10.1002/bjs.9764]
53 Yan R, Dang C. Meta-analysis of Transhiatal Esophagectomy in carcinoma of esophagogastric junction,
does it have an advantage? Int J Surg 2017; 42: 183-190 [PMID: 28343029 DOI:
10.1016/j.ijsu.2017.03.052]
54 Cuschieri A. Endoscopic subtotal oesophagectomy for cancer using the right thoracoscopic approach.
Surg Oncol 1993; 2 Suppl 1: 3-11 [PMID: 8252219 DOI: 10.1016/0960-7404(93)90052-Z]
55 Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy-assisted Billroth I gastrectomy. Surg Laparosc
Endosc 1994; 4: 146-148 [PMID: 8180768]
56 Zhou C, Zhang L, Wang H, Ma X, Shi B, Chen W, He J, Wang K, Liu P, Ren Y. Superiority of Minimally
Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal
Cancer: A Meta-Analysis. PLoS One 2015; 10: e0132889 [PMID: 26196135 DOI:
10.1371/journal.pone.0132889]
57 Wiesel O, Whang B, Cohen D, Fisichella PM. Minimally Invasive Esophagectomy for Adenocarcinomas
of the Gastroesophageal Junction and Distal Esophagus: Notes on Technique. J Laparoendosc Adv Surg
Tech A 2017; 27: 162-169 [PMID: 27858584 DOI: 10.1089/lap.2016.0430]
58 Irino T, Tsai JA, Ericson J, Nilsson M, Lundell L, Rouvelas I. Thoracoscopic side-to-side
esophagogastrostomy by use of linear stapler-a simplified technique facilitating a minimally invasive Ivor-
Lewis operation. Langenbecks Arch Surg 2016; 401: 315-322 [PMID: 26960591 DOI:
10.1007/s00423-016-1396-1]
59 Luketich JD, Alvelo-Rivera M, Buenaventura PO, Christie NA, McCaughan JS, Litle VR, Schauer PR,
Close JM, Fernando HC. Minimally invasive esophagectomy: outcomes in 222 patients. Ann Surg 2003;
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
577
238: 486-94; discussion 494-5 [PMID: 14530720 DOI: 10.1097/01.sla.0000089858.40725.68]
60 van Workum F, Berkelmans GH, Klarenbeek BR, Nieuwenhuijzen GAP, Luyer MDP, Rosman C.
McKeown or Ivor Lewis totally minimally invasive esophagectomy for cancer of the esophagus and
gastroesophageal junction: systematic review and meta-analysis. J Thorac Dis 2017; 9: S826-S833 [PMID:
28815080 DOI: 10.21037/jtd.2017.03.173]
61 van Workum F, Bouwense SA, Luyer MD, Nieuwenhuijzen GA, van der Peet DL, Daams F,
Kouwenhoven EA, van Det MJ, van den Wildenberg FJ, Polat F, Gisbertz SS, Henegouwen MI,
Heisterkamp J, Langenhoff BS, Martijnse IS, Grutters JP, Klarenbeek BR, Rovers MM, Rosman C.
Intrathoracic versus Cervical ANastomosis after minimally invasive esophagectomy for esophageal cancer:
study protocol of the ICAN randomized controlled trial. Trials 2016; 17: 505 [PMID: 27756419 DOI:
10.1186/s13063-016-1636-2]
62 Parry K, Haverkamp L, Bruijnen RC, Siersema PD, Ruurda JP, van Hillegersberg R. Surgical treatment of
adenocarcinomas of the gastro-esophageal junction. Ann Surg Oncol 2015; 22: 597-603 [PMID: 25190126
DOI: 10.1245/s10434-014-4047-1]
63 Ai B, Zhang Z, Liao Y. Laparoscopic and thoracoscopic esophagectomy with intrathoracic anastomosis for
middle or lower esophageal carcinoma. J Thorac Dis 2014; 6: 1354-1357 [PMID: 25276383 DOI:
10.3978/j.issn.2072-1439.2014.07.38]
64 Singh T, Sanaka MR, Thota PN. Endoscopic therapy for Barrett's esophagus and early esophageal cancer:
Where do we go from here? World J Gastrointest Endosc 2018; 10: 165-174 [PMID: 30283599 DOI:
10.4253/wjge.v10.i9.165]
65 Meng FS, Zhang ZH, Wang YM, Lu L, Zhu JZ, Ji F. Comparison of endoscopic resection and
gastrectomy for the treatment of early gastric cancer: a meta-analysis. Surg Endosc 2016; 30: 3673-3683
[PMID: 26659235 DOI: 10.1007/s00464-015-4681-0]
66 Osumi H, Fujisaki J, Omae M, Shimizu T, Yoshio T, Ishiyama A, Hirasawa T, Tsuchida T, Yamamoto Y,
Kawachi H, Yamamoto N, Igarashi M. Clinicopathological features of Siewert type II adenocarcinoma:
comparison of gastric cardia adenocarcinoma and Barrett's esophageal adenocarcinoma following
endoscopic submucosal dissection. Gastric Cancer 2017; 20: 663-670 [PMID: 27783167 DOI:
10.1007/s10120-016-0653-x]
67 Ishihara R, Oyama T, Abe S, Takahashi H, Ono H, Fujisaki J, Kaise M, Goda K, Kawada K, Koike T,
Takeuchi M, Matsuda R, Hirasawa D, Yamada M, Kodaira J, Tanaka M, Omae M, Matsui A, Kanesaka T,
Takahashi A, Hirooka S, Saito M, Tsuji Y, Maeda Y, Yamashita H, Oda I, Tomita Y, Matsunaga T, Terai
S, Ozawa S, Kawano T, Seto Y. Risk of metastasis in adenocarcinoma of the esophagus: a multicenter
retrospective study in a Japanese population. J Gastroenterol 2017; 52: 800-808 [PMID: 27757547 DOI:
10.1007/s00535-016-1275-0]
68 Park CH, Kim EH, Kim HY, Roh YH, Lee YC. Clinical outcomes of endoscopic submucosal dissection
for early stage esophagogastric junction cancer: a systematic review and meta-analysis. Dig Liver Dis
2015; 47: 37-44 [PMID: 25454708 DOI: 10.1016/j.dld.2014.10.011]
69 Gong EJ, Kim DH, Ahn JY, Jung KW, Lee JH, Choi KD, Song HJ, Lee GH, Jung HY, Kim HS, Lee IS,
Kim BS, Yoo MW, Oh ST, Yook JH, Kim BS. Comparison of long-term outcomes of endoscopic
submucosal dissection and surgery for esophagogastric junction adenocarcinoma. Gastric Cancer 2017;
20: 84-91 [PMID: 27995482 DOI: 10.1007/s10120-016-0679-0]
70 Abe S, Ishihara R, Takahashi H, Ono H, Fujisaki J, Matsui A, Takahashi A, Goda K, Kawada K, Koike T,
Takeuchi M, Tsuji Y, Hirasawa D, Oyama T. Long-term outcomes of endoscopic resection and
metachronous cancer after endoscopic resection for adenocarcinoma of the esophagogastric junction in
Japan. Gastrointest Endosc 2019; 89: 1120-1128 [PMID: 30576649 DOI: 10.1016/j.gie.2018.12.010]
WJGO https://www.wjgnet.com
August 15, 2019 Volume 11 Issue 8
Zhang S et al. Current surgical treatment of EGJ cancer
578
Published By Baishideng Publishing Group Inc
7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Telephone: +1-925-2238242
Fax: +1-925-2238243
E-mail: bpgoffice@wjgnet.com
Help Desk:https://www.f6publishing.com/helpdesk
https://www.wjgnet.com
© 2019 Baishideng Publishing Group Inc. All rights reserved.
