Lotti Marco MD - Cancer of the Oesophago-Gastric Junction

Carcinoma of the Gastric Cardia:
Transhiatal Approach
Marco Lotti MD
Division of Advanced Surgical Oncology
Department of General Surgery 1
Papa Giovanni XXIII Hospital – Bergamo - Italy
XXVII CONGRESSO NAZIONALE SPIGC
SOCIETÀ POLISPECIALISTICA ITALIANA DEI GIOVANI CHIRURGHI
Brescia, 11-13 giugno 2015
PROGRAMMA SCIENTIFICO
11 - 13 giugno 2015
©2015 Marco Lotti – mlotti@hpg23.it

Recurrence with surgery alone
Percentage of Siewert I Siewert II Siewert III
Perioperative Deaths 3 - 5 2.5 -5 5 – 6.5
Recurrence at 2 and 5 years 45 - 70 55 - 75 65 - 72
• haematogenous 55 55 30 - 45
• local/anastomotic 35 30 25
• peritoneal 7 15 35 -55
• lymph node 20 30 25
- coeliac axis 40 25 /
- porta 30 33 /
- retrocrural/aortocaval 10 25 80
- cervical/mediastinal 30 25 20

The Randomized Trials

• TRANSHIATAL ESOPHAGECTOMY: the tumor
and its adjacent lymph nodes were dissected
en bloc. A 3-cm-wide gastric tube was
constructed. The left gastric artery was
transected at its origin, with resection of
local lymph nodes. Celiac lymph nodes were
dissected only when there was clinical
suspicion of involvement. Anastomosis in
the neck.
• TRANSTHORACIC ESOPHAGECTOMY: the
thoracic duct, azygos vein, ipsilateral pleura,
and all periesophageal tissue in the
mediastinum were dissected en bloc. The
paracardial, lesser-curvature, left-gastric-
artery (along with lesser-curvature), celiac
trunc, common-hepatic-artery, and splenic-
artery nodes were dissected, and a gastric
tube was constructed.
• A mean (±SD) of 16±9 nodes were identified
in the resection specimen after transhiatal
resection, and 31± 14 after transthoracic
resection (p<0.001). 1662 · N Engl J Med, Vol. 347, No. 21 · November 21, 2002 · www.nejm.org
The New England Journal of Medicine
EXTENDED TRANSTHORACIC RESECTION COMPARED WITH LIMITED
TRANSHIATAL RESECTION FOR ADENOCARCINOMA OF THE ESOPHAGUS
JAN B.F. HULSCHER, M.D., JOHANNA W. VAN SANDICK, M.D., ANGELA G.E.M. DE BOER, PH.D.,
BAS P.L. WIJNHOVEN, M.D., JAN G.P. TIJSSEN, PH.D., PAUL FOCKENS, M.D., PEEP F.M. STALMEIER, PH.D.,
FIEBO J.W. TEN KATE, M.D., HERMAN VAN DEKKEN, M.D., HUUG OBERTOP, M.D., HUGO W. TILANUS, M.D.,
AND J. JAN B. VAN LANSCHOT, M.D.
ABSTRACT
Background Controversy exists about the best sur-
gical treatment for esophageal carcinoma.
Methods We randomly assigned 220 patients with
adenocarcinoma of the mid-to-distal esophagus or ad-
enocarcinoma of the gastric cardia involving the dis-
tal esophagus either to transhiatal esophagectomy or
to transthoracic esophagectomy with extended en bloc
lymphadenectomy. Principal end points were overall
survival and disease-free survival. Early morbidity and
mortality, the number of quality-adjusted life-years
gained, and cost effectiveness were also determined.
Results A total of 106 patients were assigned to un-
dergo transhiatal esophagectomy, and 114 to undergo
transthoracic esophagectomy. Demographic charac-
teristics and characteristics of the tumor were similar
in the two groups. Perioperative morbidity was higher
after transthoracic esophagectomy, but there was no
significant difference in in-hospital mortality (P=0.45).
After a median follow-up of 4.7 years, 142 patients
had died — 74 (70 percent) after transhiatal resection
and 68 (60 percent) after transthoracic resection (P=
0.12). Although the difference in survival was not sta-
tistically significant, there was a trend toward a surviv-
al benefit with the extended approach at five years:
disease-free survival was 27 percent in the transhiatal-
esophagectomy group, as compared with 39 percent
in the transthoracic-esophagectomy group (95 per-
cent confidence interval for the difference, ¡1 to 24
percent [the negative value indicates better survival
with transhiatal resection]), whereas overall survival
was 29 percent as compared with 39 percent (95 per-
percent).
Conclusions Transhiatal esophagectomy was asso-
ciated with lower morbidity than transthoracic esoph-
agectomy with extended en bloc lymphadenectomy.
Although median overall, disease-free, and quality-
adjusted survival did not differ statistically between
the groups, there was a trend toward improved long-
term survival at five years with the extended transtho-
racic approach. (N Engl J Med 2002;347:1662-9.)
Copyright © 2002 Massachusetts Medical Society.
From the Departments of Surgery (J.B.F.H., J.W.S., H.O., J.J.B.L.), Medica
Psychology (A.G.E.M.B., P.F.M.S.), Cardiology (J.G.P.T.), Gastroenterolog
(P.F.), and Pathology (F.J.W.K.), Academic Medical Center, University o
Amsterdam, Amsterdam; the Departments of Surgery (B.P.L.W., H.W.T.) and
Pathology (H.D.), Erasmus University Hospital Rotterdam, Rotterdam; and
RADIAN and Medical Technology Assessment (P.F.M.S.), Nijmegen — al
in the Netherlands. Address reprint requests to Dr. van Lanschot at the Aca
demic Medical Center at the University of Amsterdam, Department of Sur
gery, Suite G4-112, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
or at j.j.vanlanschot@amc.uva.nl.
ONG-TERM survival after surgery with cur-
ative intent for adenocarcinoma of the dista
esophagus and gastric cardia is only 20 per-
cent.1,2 Surgery is generally considered to of-
fer the best chance for cure, but opinions differ on how
to improve survival by surgery. One strategy aims at
decreasing early postoperative risk by the use of lim-
ited cervicoabdominal (transhiatal) esophagectomy
without formal lymphadenectomy. Another is in-
tended to improve long-term survival by performing
a combined cervicothoracoabdominal resection, with
wide excision of the tumor and peritumoral tissues and
extended lymph-node dissection in the posterior medi-
astinum and the upper abdomen (transthoracic esoph-
agectomy with extended en bloc lymphadenectomy).1-5
We studied whether transthoracic esophagectomy
with extended en bloc lymphadenectomy sufficiently
improves overall, disease-free, and quality-adjusted sur-
vival over the rates with transhiatal esophagectomy to
compensate for the possibly higher perioperative mor-
bidity and mortality and the increased costs of the
treatment.
METHODS
Study Design
The study was performed in two academic medical centers, each
performing more than 50 esophagectomy procedures per year. The
eligible patients had histologically confirmed adenocarcinoma of the
mid-to-distal esophagus or adenocarcinoma of the gastric cardia in
volving the distal esophagus, had no evidence of distant metastases
(including the absence of histologically confirmed tumor-positive
cervical lymph nodes and unresectable celiac lymph nodes), and
did not have unresectable local disease. These patients were random
ly assigned to undergo transhiatal esophagectomy or transthoracic
esophagectomy with extended en bloc lymphadenectomy between
April 1994 and February 2000.
Patients had to be older than 18 years of age and in adequate
physical condition to undergo surgery (as indicated by their assign
ment to American Society of Anesthesiologists class I or II6). Ex
clusion criteria were previous or coexisting cancer, previous gastric
or esophageal surgery, receipt of neoadjuvant chemotherapy or ra
L
Downloaded from nejm.org on May 25, 2015. For personal use only. No other uses without permission.
Copyright © 2002 Massachusetts Medical Society. All rights reserved.
Surgical Consequences
type I
Fig. 2.5
Different lymphadenectomy
in the mediastinum
and even in the abdomen©2015 Marco Lotti – mlotti@hpg23.it

0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival 391624334043475473110TTE
28101721323539526995THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival 391624334043475473110TTE
28101721323539526995THE
Numbers at risk
THE
TTE
FIGURE 2. Overall survival of all patients after
transhiatal (drawn line) or transthoracic (dotted
line) esophagectomy (P ϭ 0.71) based on per
protocol analysis and after exclusion of patients
who did not undergo surgical resection.
Test for interaction:
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Outcome is overall survival
Type I (n=90)
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Type II (n=115)
Lokalisation:
# positive nodes:
p=0.39
p=0.07
0 (n=55)
Lokalisation:
# positive nodes:
p=0.39
p=0.07
1-8 (n=104)
Lokalisation:
# positive nodes:
p=0.39
p=0.07
9+ (n=46)
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Lokalisation:
# positive nodes:
p=0.39
p=0.07
Location
>8 (n=46)
Omloo et al Annals of Surgery • Volume 246, Number 6, December 2007
Extended Transthoracic Resection Compared With Limited
Transhiatal Resection for Adenocarcinoma of the Mid/Distal
Esophagus
Five-Year Survival of a Randomized Clinical Trial
Jikke M. T. Omloo, MD,* Sjoerd M. Lagarde, MD,* Jan B. F. Hulscher, MD,*
Johannes B. Reitsma, MD, PhD,† Paul Fockens, MD, PhD,‡ Herman van Dekken, MD, PhD,§
Fiebo J. W. ten Kate, MD,¶ Huug Obertop, MD,ʈ Hugo W. Tilanus, MD, PhD,ʈ
and J. Jan B. van Lanschot, MD࿣
Objective: To determine whether extended transthoracic esopha-
gectomy for adenocarcinoma of the mid/distal esophagus improves
long-term survival.
Background: A randomized trial was performed to compare surgi-
cal techniques. Complete 5-year survival data are now available.
Methods: A total of 220 patients with adenocarcinoma of the distal
esophagus (type I) or gastric cardia involving the distal esophagus
(type II) were randomly assigned to limited transhiatal esophagec-
tomy or to extended transthoracic esophagectomy with en bloc
lymphadenectomy. Patients with peroperatively irresectable/incur-
able cancer were excluded from this analysis (n ϭ 15). A total of 95
patients underwent transhiatal esophagectomy and 110 patients
underwent transthoracic esophagectomy.
Results: After transhiatal and transthoracic resection, 5-year sur-
vival was 34% and 36%, respectively (P ϭ 0.71, per protocol
analysis). In a subgroup analysis, based on the location of the
primary tumor according to the resection specimen, no overall
survival benefit for either surgical approach was seen in 115 patients
with a type II tumor (P ϭ 0.81). In 90 patients with a type I tumor,
a survival benefit of 14% was seen with the transthoracic approach
(51% vs. 37%, P ϭ 0.33). There was evidence that the treatment
effect differed depending on the number of positive lymph nodes in
the resection specimen (test for interaction P ϭ 0.06). In patients
(n ϭ 55) without positive nodes locoregional disease-free survival
after transhiatal esophagectomy was comparable to that after trans-
thoracic esophagectomy (86% and 89%, respectively). The same
was true for patients (n ϭ 46) with more than 8 positive nodes (0%
in both groups). Patients (n ϭ 104) with 1 to 8 positive lymph nodes
in the resection specimen showed a 5-year locoregional disease-free
survival advantage if operated via the transthoracic route (23% vs.
64%, P ϭ 0.02).
Conclusion: There is no significant overall survival benefit for
either approach. However, compared with limited transhiatal resec-
tion extended transthoracic esophagectomy for type I esophageal
adenocarcinoma shows an ongoing trend towards better 5-year
survival. Moreover, patients with a limited number of positive
lymph nodes in the resection specimen seem to benefit from an
extended transthoracic esophagectomy.
(Ann Surg 2007;246: 992–1001)
The incidence of adenocarcinoma of the esophagus and gas-
troesophageal junction is rapidly rising. It is an aggressive
disease with early lymphatic and hematogenous dissemination.
Long-term survival rates barely exceed 25%, even after surgery
with curative intent.1,2
Surgery is still considered the best cura-
tive treatment option. However, much controversy concerning
the optimal surgical approach exists.
Two main operation techniques are currently advo-
cated. Limited transhiatal esophagectomy (THE) (without
formal lymphadenectomy) aims at decreasing early postop-
erative morbidity and mortality. Whereas extended transtho-
racic esophagectomy (TTE) with en bloc lymphadenectomy
is intended to improve long-term survival by performing a
combined (cervico) thoracoabdominal resection, with wide
excision of the tumor and peritumoral tissues and extended
lymph node dissection in the posterior mediastinum and
upper abdomen.
From the *Departments of Surgery, †Clinical Epidemiology, Biostatistics,
and Bioinformatics, and ‡Gastroenterology, Academic Medical Center,
University of Amsterdam, Amsterdam, The Netherlands; §Department of
Pathology, Erasmus Medical Center, Rotterdam, The Netherlands; ¶De-
partment of Pathology, Academic Medical Center, University of Amster-
dam, Amsterdam, The Netherlands; and ࿣Department of Surgery, Eras-
mus Medical Center, Rotterdam, The Netherlands.
Supported by ZonMw Health Care Efficiency Research (945-04-510; to
J. M. T. O.).
Supported by the Maag Lever Darm Stichting (Dutch Digestive Foundation,
04-77; to S. M. L.).
Supported by the Dutch Health Care Insurance Funds Council (1996-041; to
J. B. F. H.).
Reprints: Jikke M. T. Omloo, Department of Surgery, Academic Medical
Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,
The Netherlands. E-mail: j.m.omloo@amc.uva.nl.
Copyright © 2007 by Lippincott Williams & Wilkins
ISSN: 0003-4932/07/24606-0992
DOI: 10.1097/SLA.0b013e31815c4037
Annals of Surgery • Volume 246, Number 6, December 2007992
1662 · N Engl J Med, Vol. 347, No. 21 · November 21, 2002 · www.nejm.org
ABSTRACT
percent).
From the Departments of Surgery (J.B.F.H., J.W.S., H.O., J.J.B.L.), Medical
Psychology (A.G.E.M.B., P.F.M.S.), Cardiology (J.G.P.T.), Gastroenterology
(P.F.), and Pathology (F.J.W.K.), Academic Medical Center, University of
RADIAN and Medical Technology Assessment (P.F.M.S.), Nijmegen — all
in the Netherlands. Address reprint requests to Dr. van Lanschot at the Aca-
demic Medical Center at the University of Amsterdam, Department of Sur-
gery, Suite G4-112, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands,
ative intent for adenocarcinoma of the distal
treatment.
METHODS
Study Design
mid-to-distal esophagus or adenocarcinoma of the gastric cardia in-
did not have unresectable local disease. These patients were random-
physical condition to undergo surgery (as indicated by their assign-
ment to American Society of Anesthesiologists class I or II6). Ex-
or esophageal surgery, receipt of neoadjuvant chemotherapy or ra-
L
t). Local–regional recurrence occurred in 14 per-
and 12 percent of patients, respectively; distant re-
ence in 25 percent and 18 percent; and both in 18
cent and 19 percent (P=0.60). For the transhiatal
transthoracic procedures, the median disease-free
rval was 1.4 years (95 percent confidence inter-
0.8 to 2.0) and 1.7 years (95 percent confidence
rval, 0.7 to 2.7), respectively (P=0.15) (Fig. 1).
estimated rate of disease-free survival at five years
27 percent (95 percent confidence interval, 19 to
percent) after transhiatal resection, as compared
h 39 percent (95 percent confidence interval, 30 to
percent) after transthoracic resection. The 95 per-
t confidence interval for the difference in the rates
¡1 percent to 24 percent (the negative value indi-
s that survival was better with transhiatal resection).
t the end of follow-up, 142 patients had died —
cent) and 68 in the transthoracic group (60 percent;
P=0.12). Thirteen patients died of causes unrelated
to cancer. The median overall survival was 1.8 years (95
percent confidence interval, 1.2 to 2.4) after transhi-
atal resection and 2.0 years (95 percent confidence in-
terval, 1.1 to 2.8) after transthoracic resection with ex-
tended en bloc lymphadenectomy (P=0.38) (Fig. 2).
The estimated rate of overall survival at five years was
29 percent (95 percent confidence interval, 20 to 38
percent) after transhiatal resection, as compared with
39 percent (95 percent confidence interval, 30 to 48
percent) after transthoracic resection. The 95 percent
confidence interval for the difference was ¡3 percent
to 23 percent. The median number of quality-adjust-
ed life-years after transhiatal resection was 1.5 (95 per-
cent confidence interval, 0.8 to 2.1), as compared with
1.8 (95 percent confidence interval, 1.1 to 2.4) after
Figure 1. Kaplan–Meier Curves Showing Disease-free Survival among Patients Randomly Assigned to Transhiatal
Esophagectomy or Transthoracic Esophagectomy with Extended en Bloc Lymphadenectomy.
100
80
60
40
20
0
876543210
Years
Transhiatal esophagectomy
CumulativeDisease-freeSurvival(%)
NO. AT RISK
Transhiatal
mesophagectomy
Transthoracic
mesophagectomy
106
114
68
69
47
53
32
39
20
31
15
20
11
13
4
7
Transthoracic esophagectomy
Five years later the survival benefit
is less than expected
“Although survival did not differ statistically
between the groups, there was
a trend toward improved 5y survival
with the extended transthoracic approach.”
“There is no significant survival benefit for
either approach. However, transthoracic
esoph. for type I esophageal adk shows an
ongoing trend towards better 5y survival.” ©2015 Marco Lotti – mlotti@hpg23.it

Esophagus
long-term survival.
64%, P ϭ 0.02).
(Ann Surg 2007;246: 992–1001)
upper abdomen.
J. M. T. O.).
04-77; to S. M. L.).
J. B. F. H.).
ISSN: 0003-4932/07/24606-0992
DOI: 10.1097/SLA.0b013e31815c4037
ABSTRACT
percent).
From the Departments of Surgery (J.B.F.H., J.W.S., H.O., J.J.B.L.), Medical
Psychology (A.G.E.M.B., P.F.M.S.), Cardiology (J.G.P.T.), Gastroenterology
(P.F.), and Pathology (F.J.W.K.), Academic Medical Center, University of
RADIAN and Medical Technology Assessment (P.F.M.S.), Nijmegen — all
in the Netherlands. Address reprint requests to Dr. van Lanschot at the Aca-
demic Medical Center at the University of Amsterdam, Department of Sur-
gery, Suite G4-112, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands,
ative intent for adenocarcinoma of the distal
treatment.
METHODS
Study Design
mid-to-distal esophagus or adenocarcinoma of the gastric cardia in-
did not have unresectable local disease. These patients were random-
physical condition to undergo surgery (as indicated by their assign-
ment to American Society of Anesthesiologists class I or II6). Ex-
or esophageal surgery, receipt of neoadjuvant chemotherapy or ra-
L
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
24101520242426273347TTE
145912161920263343THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
24101520242426273347TTE
145912161920263343THE
Numbers at risk
THE
TTE
0,2
0,4
0,6
0,8
1,0
survival
THE
TTE
0,2
0,4
0,6
0,8
1,0
survival
THE
TTE
A
B
FI
I a
ta
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
24101520242426273347TTE
145912161920263343THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
24101520242426273347TTE
145912161920263343THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7 8 9 10 11
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
survival
Numbers at risk
THE
TTE
A
B
FI
I a
ta
es
pa
tri
“Patients were stratified to a type 1 and type 2,
according to the endoscopy report.
The gastroenterologists and surgeons were perhaps a
bit too prone to call a tumor type I esophageal. For
that reason several tumors were called esophageal
when they were actually in the gastrocardial region.
We thought it was better to look at the actual
localization site in the pathology report and that is
the reason for the difference in numbers.”
“No difference is not no results” is
difficult to accept

0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
locoregionaldiseasefreesurvival
361012202627TTE
37913202528THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
361012202627TTE
37913202528THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
27816243352TTE
1456173252THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
27816243352TTE
1456173252THE
Numbers at risk
THE
TTE
01931TTE
12615THE
Numbers at risk
THE
TTE
0
0
0 1 2 3 4 5
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
THE
TTE
A B
C
FIGURE 5. A, Locoregional disease-free survival of all patients without positive lymph nodes in the resection specimen after
transhiatal (drawn line) or transthoracic (dotted line) esophagectomy (P ϭ 0.64). B, Locoregional disease-free survival of all
patients with 1 to 8 positive lymph nodes in the resection specimen after transhiatal (drawn line) or transthoracic (dotted line)
esophagectomy (P ϭ 0.02). C, Locoregional disease-free survival of all patients with more than 8 positive lymph nodes in the
resection specimen after transhiatal (drawn line) or transthoracic (dotted line) esophagectomy (P ϭ 0.24).
Esophagus
long-term survival.
64%, P ϭ 0.02).
(Ann Surg 2007;246: 992–1001)
upper abdomen.
J. M. T. O.).
04-77; to S. M. L.).
J. B. F. H.).
ISSN: 0003-4932/07/24606-0992
DOI: 10.1097/SLA.0b013e31815c4037
“Based on this
best available
evidence, we
favor an extended
transthoracic
procedure for
type I esophageal
carcinoma,
especially if there
is a limited
number of
suspicious nodes,
and a (limited)
transhiatal
procedure for
type II carcinoma
of the gastric
cardia. “

0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
361012202627TTE
37913202528THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
361012202627TTE
37913202528THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
27816243352TTE
1456173252THE
Numbers at risk
THE
TTE
0 1 2 3 4 5 6 7
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
27816243352TTE
1456173252THE
Numbers at risk
THE
TTE
01931TTE
12615THE
Numbers at risk
THE
TTE
0
0
0 1 2 3 4 5
follow-up (years)
0,0
0,2
0,4
0,6
0,8
1,0
THE
TTE
A B
C
FIGURE 5. A, Locoregional disease-free survival of all patients without positive lymph nodes in the resection specimen after
transhiatal (drawn line) or transthoracic (dotted line) esophagectomy (P ϭ 0.64). B, Locoregional disease-free survival of all
patients with 1 to 8 positive lymph nodes in the resection specimen after transhiatal (drawn line) or transthoracic (dotted line)
esophagectomy (P ϭ 0.02). C, Locoregional disease-free survival of all patients with more than 8 positive lymph nodes in the
resection specimen after transhiatal (drawn line) or transthoracic (dotted line) esophagectomy (P ϭ 0.24).
Esophagus
long-term survival.
64%, P ϭ 0.02).
(Ann Surg 2007;246: 992–1001)
upper abdomen.
J. M. T. O.).
04-77; to S. M. L.).
J. B. F. H.).
ISSN: 0003-4932/07/24606-0992
DOI: 10.1097/SLA.0b013e31815c4037
“Based on this
best available
evidence, we
favor an extended
transthoracic
procedure for
type I esophageal
carcinoma,
especially if there
is a limited
number of
suspicious nodes,
and a (limited)
transhiatal
procedure for
type II carcinoma
of the gastric
cardia. “
5yr OS:
TTE 39%
THE 19%
Meaning:
TTE is useful to
9% of pts who
undergo TTE
Look: this is
“locoregional disease free”
survival (!!!)

2.2.4
type I II III
Fig. 2.5
TRANSHIATAL APPROACH: total gastrectomy
with D2 lymphadenectomy (including
splenectomy). Additional dissection of the
lymph nodes along the left inferior phrenic
vessels and the para-aortic nodes lateral to
the aorta and above the left renal vein was
done in curable patients. Mediastinal
resection included the lower oesophagus and
only the perioesophageal lymph nodes.
TRANSTHORACIC APPROACH: the same
procedure as that for TH was done in the
abdominal cavity, including
lymphadenectomy. Through an oblique
incision over the left thorax a thorough
mediastinal nodal dissection below the left
inferior pulmonary vein was undertaken with
oesophagectomy of sufficient length.
A median of 68 nodes were identified in the
resection specimen after transhiatal resection,
and 60 after transthoracic resection.
644 http://oncology.thelancet.com Vol 7 August 2006
Left thoracoabdominal approach versus abdominal-
transhiatal approach for gastric cancer of the cardia or
subcardia: a randomised controlled trial
Mitsuru Sasako,Takeshi Sano, Seiichiro Yamamoto, Motonori Sairenji, Kuniyoshi Arai,Taira Kinoshita, Atsushi Nashimoto, Masahiro Hiratsuka,
for the Japan Clinical Oncology Group (JCOG9502)
Summary
Background Because of the inaccessibility of mediastinal nodal metastases, the left thoracoabdominal approach (LTA)
has often been used to treat gastric cancer of the cardia or subcardia. In a randomised phase III study, we aimed to
compare LTA with the abdominal-transhiatal approach (TH) in the treatment of these tumours.
Methods Between July, 1995, and December, 2003, 167 patients were enrolled from 27 Japanese hospitals and randomly
assigned to TH (n=82) or LTA (n=85). The primary endpoint was overall survival, and secondary endpoints were
disease-free survival, postoperative morbidity and hospital mortality, and postoperative symptoms and change of
respiratory function. The projected sample size was 302. After the first interim analysis, the predicted probability of
LTA having a significantly better overall survival than TH at the final analysis was only 3·65%, and the trial was closed
immediately. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number
NCT00149266.
Findings 5-year overall survival was 52·3% (95% CI 40·4–64·1) in the TH group and 37·9% (26·1–49·6) in the LTA
group. The hazard ratio of death for LTA compared with TH was 1·36 (0·89–2·08, p=0·92). Three patients died in
hospital after LTA but none after TH. Morbidity was worse after LTA than after TH.
Interpretation Because LTA does not improve survival after TH and leads to increased morbidity in patients with
cancer of the cardia or subcardia, LTA cannot be justified to treat these tumours.
Introduction
By contrast with the notable decrease in the incidence of
distal gastric cancer, frequency of adenocarcinoma in the
oesophagogastric junction has increased, especially in
developed countries.1–3
The Siewert classification for
these tumours is now widely accepted.4
Studies of
adjuvant treatment for gastric cancer with chemotherapy
or chemoradiotherapy have included tumours in the
oesophagogastric junction.5,6
However, no evidence
suggests that oesophagogastric-junction tumours can be
treated in the same way as gastric cancers; if thoracotomy
is mandatory for oesophagogastric-junction tumours,
they should not be included in studies on the treatment
of gastric cancers. So far, only one prospective randomised
controlled trial7
has been undertaken to compare the
effects of surgical treatments in Siewert type 1 and 2
tumours in the oesophagogastric junction. Although the
trial was slightly underpowered, it suggested that
extended transthoracic resection resulted in better
survival than a restricted transhiatal resection. However,
a systematic review8
comparing surgical treatments for
lower oesophageal carcinoma showed a higher morbidity
for transthoracic resection than for transhiatal resection,
but with similar survival.
In eastern Asian countries, including Japan, most
tumours in the oesophagogastric junction are of Siewert
type 2 and 3.9
The occurrence of lower mediastinal
lymph-node metastasis from type 2 and 3 tumours is
reported to be 10–40%.10–16
Some researchers10,11
claim that
a thoracotomy is needed to thoroughly dissect the
mediastinal nodes and to obtain a safe surgical margin,
although mediastinal lymph-node metastasis is an
indicator of poor prognosis. Other studies12,13
recommend
the use of a transhiatal resection, because patients with
mediastinal-lymph-node metastasis have poor prognosis
even if a more extensive procedure was done. Advances
in circular stapling devices have enabled surgeons to
make safe intrathoracic or mediastinal anastomosis
without thoracotomy.
In 1995, the Gastric Cancer Surgical Study Group of the
Japan Clinical Oncology Group (GCSSG/JCOG) initiated
a multicentre, randomised controlled trial with the aim
to compare the effects of the left thoracoabdominal
approach (LTA) with the abdominal-transhiatal approach
(TH) on patients with cancer of the cardia or subcardia
(JCOG 9502).
Methods
Patients
Our study was designed as a multicentre, prospective,
randomised phase III trial. The study protocol was
approved by the clinical trial review committee of JCOG
and the institutional review boards of all 27 participating
Japanese hospitals before the initiation of the study, and
all patients provided written informed consent. Eligibility
criteria included: histologically proven adenocarcinoma
Lancet Oncol 2006; 7: 644–51
Published Online July 12, 2006
DOI:10.1016/S1470-2045(06)
70766-5
See Reflection and Reaction
page 613
National Cancer Centre,Tokyo,
Japan (Prof M Sasako MD,
T Sano MD, SYamamoto PhD);
Kanagawa Cancer Centre,
Kanagawa, Japan
(M Sairenji MD); Metropolitan
Komagome Hospital,Tokyo,
Japan (K Arai MD); National
Cancer Centre East Hospital,
Kashiwa, Japan
(T Kinoshita MD); Niigata
Cancer Centre Hospital,
Niigata, Japan
(A Nashimoto MD); and Osaka
Medical Centre for Cancer and
Cardiovascular Diseases, Osaka,
Japan (M Hiratsuka MD)
Correspondence to:
Prof Mitsuru Sasako, National
Cancer Centre Hospital,Tokyo
104-0045, Japan
msasako@gan2.ncc.go.jp
2.2.4
type I II III
Fig. 2.5
Different lymphadenectomy
in the lower mediastinum©2015 Marco Lotti – mlotti@hpg23.it

er
or
as
es
d
d
d
TH (n=82) LTA (n=85)*
Type of gastrectomy
Total 79 80
Proximal 3 3
Not resected 0 2
Reconstruction method
Roux-en-Y 75 76
Interposition 5 3
Other 2 4
Length of resected oesophagus (cm)
Median (range) 4·2 (2·0–9·5) 4·5 (2·0–8·5)
Splenectomy
Yes 78 81
No 4 4
Pancreatic-tail resection
Yes 22 13
No 60 72
Thoracotomy
Intercostal 3 79
Transabdominal 10 3
None 69 3
Dissected lymph nodes (median [range])
Total 68 (14–147) 60 (16–160)
Mediastinal 2 (0–13) 8 (0–24)
Para-aortic 7 (0–63) 6 (0–60)
Operation time (min)
Median (range) 305 (100–620) 338 (73–635)
Blood loss (mL)
Median (range) 673 (55–3500) 655 (55–2174)
Allogeneic blood transfusion
Yes 25 39
No 57 46
Data are number of patients unless stated otherwise. *Two patients undergoing
(Continued from previous page)
Oesophageal invasion (cm)
Median (range) 1·6 (0–4·5) 1·2 (0–7·0)
Washing cytology
Negative 69 73
Positive 11 9
Not done 2 3
Residual tumour
R0 76 75
R1/2 6 10
Para-aortic nodal metastasis
Positive 13 9
Negative 59 64
Not dissected 10 12
Mediastinal nodal metastasis
Positive 3 9†
Negative 79 74
Not dissected 0 2
Data are numberof patientsunless statedotherwise. *Data not available fortwo
patients in LTA groupwhodid notundergo resection becauseof peritoneal seeding.
†Includes five patientswith Siewerttype 2tumours and fourwithothertypes.
Left thoracoabdominal approach versus abdominal-
transhiatal approach for gastric cancer of the cardia or
subcardia: a randomised controlled trial
Mitsuru Sasako,Takeshi Sano, Seiichiro Yamamoto, Motonori Sairenji, Kuniyoshi Arai,Taira Kinoshita, Atsushi Nashimoto, Masahiro Hiratsuka,
Summary
Background Because of the inaccessibility of mediastinal nodal metastases, the left thoracoabdominal approach (LTA)
has often been used to treat gastric cancer of the cardia or subcardia. In a randomised phase III study, we aimed to
compare LTA with the abdominal-transhiatal approach (TH) in the treatment of these tumours.
Methods Between July, 1995, and December, 2003, 167 patients were enrolled from 27 Japanese hospitals and randomly
assigned to TH (n=82) or LTA (n=85). The primary endpoint was overall survival, and secondary endpoints were
disease-free survival, postoperative morbidity and hospital mortality, and postoperative symptoms and change of
respiratory function. The projected sample size was 302. After the first interim analysis, the predicted probability of
LTA having a significantly better overall survival than TH at the final analysis was only 3·65%, and the trial was closed
immediately. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number
NCT00149266.
Findings 5-year overall survival was 52·3% (95% CI 40·4–64·1) in the TH group and 37·9% (26·1–49·6) in the LTA
group. The hazard ratio of death for LTA compared with TH was 1·36 (0·89–2·08, p=0·92). Three patients died in
hospital after LTA but none after TH. Morbidity was worse after LTA than after TH.
Interpretation Because LTA does not improve survival after TH and leads to increased morbidity in patients with
cancer of the cardia or subcardia, LTA cannot be justified to treat these tumours.
Introduction
By contrast with the notable decrease in the incidence of
distal gastric cancer, frequency of adenocarcinoma in the
oesophagogastric junction has increased, especially in
developed countries.1–3
The Siewert classification for
these tumours is now widely accepted.4
Studies of
adjuvant treatment for gastric cancer with chemotherapy
or chemoradiotherapy have included tumours in the
oesophagogastric junction.5,6
However, no evidence
suggests that oesophagogastric-junction tumours can be
treated in the same way as gastric cancers; if thoracotomy
is mandatory for oesophagogastric-junction tumours,
they should not be included in studies on the treatment
of gastric cancers. So far, only one prospective randomised
controlled trial7
has been undertaken to compare the
effects of surgical treatments in Siewert type 1 and 2
tumours in the oesophagogastric junction. Although the
trial was slightly underpowered, it suggested that
extended transthoracic resection resulted in better
survival than a restricted transhiatal resection. However,
a systematic review8
comparing surgical treatments for
lower oesophageal carcinoma showed a higher morbidity
for transthoracic resection than for transhiatal resection,
but with similar survival.
In eastern Asian countries, including Japan, most
tumours in the oesophagogastric junction are of Siewert
type 2 and 3.9
The occurrence of lower mediastinal
reported to be 10–40%.10–16
Some researchers10,11
claim that
a thoracotomy is needed to thoroughly dissect the
mediastinal nodes and to obtain a safe surgical margin,
although mediastinal lymph-node metastasis is an
indicator of poor prognosis. Other studies12,13
recommend
the use of a transhiatal resection, because patients with
mediastinal-lymph-node metastasis have poor prognosis
even if a more extensive procedure was done. Advances
in circular stapling devices have enabled surgeons to
make safe intrathoracic or mediastinal anastomosis
without thoracotomy.
In 1995, the Gastric Cancer Surgical Study Group of the
Japan Clinical Oncology Group (GCSSG/JCOG) initiated
a multicentre, randomised controlled trial with the aim
to compare the effects of the left thoracoabdominal
approach (LTA) with the abdominal-transhiatal approach
(TH) on patients with cancer of the cardia or subcardia
(JCOG 9502).
Methods
Patients
Our study was designed as a multicentre, prospective,
randomised phase III trial. The study protocol was
approved by the clinical trial review committee of JCOG
and the institutional review boards of all 27 participating
Japanese hospitals before the initiation of the study, and
all patients provided written informed consent. Eligibility
Lancet Oncol 2006; 7: 644–51
Published Online July 12, 2006
DOI:10.1016/S1470-2045(06)
70766-5
See Reflection and Reaction
page 613
National Cancer Centre,Tokyo,
Japan (Prof M Sasako MD,
T Sano MD, SYamamoto PhD);
Kanagawa Cancer Centre,
Kanagawa, Japan
(M Sairenji MD); Metropolitan
Komagome Hospital,Tokyo,
Japan (K Arai MD); National
Cancer Centre East Hospital,
Kashiwa, Japan
(T Kinoshita MD); Niigata
Cancer Centre Hospital,
Niigata, Japan
(A Nashimoto MD); and Osaka
Medical Centre for Cancer and
Cardiovascular Diseases, Osaka,
Japan (M Hiratsuka MD)
Correspondence to:
Prof Mitsuru Sasako, National
Cancer Centre Hospital,Tokyo
104-0045, Japan
msasako@gan2.ncc.go.jp
TH LTA

cT2 20 20
cT3/4 62 65
Pathological tumour category†‡§
pT1b 2 1
pT2a 10 6
pT2b 24 35
pT3 39 37
pT4 7 4
Pathological node category†‡
pN0 14 15
pN1 24 27
pN2 30 25
pN3/4 14 16
Pathological node category†§
pN0 14 15
pN1 35 28
pN2 16 26
pN3 17 14
No. of positive nodes*† 5 (0–53) 5 (0–52)
Histological oesophageal invasion (cm)*† 1⋅6 (0–4⋅5) 1⋅2 (0–7⋅0)
Residual tumour
R0 76 75
R1/2 6 10
*Values are median (range). †Data not available for two patients in the left
thoracoabdominal (LTA) group who did not undergo surgical resection
owing to M1 disease. ‡Japanese Classification of Gastric Carcinoma, 12th
edition16; §International Union Against Cancer (UICC) TNM
classification, 6th edition17
. TH, transhiatal; OGJ, oesophagogastric
junction.
disease), no further treatment was allowed unless recur-
a Overall survival
0
0·1
No. at risk
TH
LTA
76
75
b Disease-free survival
56
49
46
37
41
33
37
27
36
25
35
25
31
20
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
1 2 3 4 5
Disease-freesurvival
6 7
Fig. 2 Kaplan–Meier curves of a overall and b dis
survival in all randomized patients by treatment g
transhiatal approach; LTA, left thoracoabdomina
a Hazard ratio (HR) 1⋅42 (95 per cent c.i. 0⋅98 to
and P = 0⋅060, 1- and 2-sided log rank test respec
1⋅28 (0⋅87 to 1⋅89; P = 0⋅892 and P = 0⋅215, 1- an
rank test respectively)
Histological type†
Differentiated 42 43
Undifferentiated 40 40
Clinical tumour category‡§
cT2 20 20
cT3/4 62 65
pT1b 2 1
pT2a 10 6
pT2b 24 35
pT3 39 37
pT4 7 4
pN0 14 15
pN1 24 27
pN2 30 25
pN3/4 14 16
pN0 14 15
pN1 35 28
pN2 16 26
pN3 17 14
No. of positive nodes*† 5 (0–53) 5 (0–52)
Histological oesophageal invasion (cm)*† 1⋅6 (0–4⋅5) 1⋅2 (0–7⋅0)
Residual tumour
R0 76 75
R1/2 6 10
*Values are median (range). †Data not available for two patients in the left
thoracoabdominal (LTA) group who did not undergo surgical resection
owing to M1 disease. ‡Japanese Classification of Gastric Carcinoma, 12th
edition16; §International Union Against Cancer (UICC) TNM
classification, 6th edition17
. TH, transhiatal; OGJ, oesophagogastric
0
No. at risk
TH
LTA
82
85
a Overall survival
72
63
61
52
51
44
47
38
42
31
40
28
37
24
1 2 3 4 5 6 7
0
0·1
No. at risk
TH
LTA
76
75
b Disease-free survival
56
49
46
37
41
33
37
27
36
25
35
25
31
20
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
1 2 3 4 5
6 7
Fig. 2 Kaplan–Meier curves of a overall and b dis
survival in all randomized patients by treatment g
transhiatal approach; LTA, left thoracoabdomina
a Hazard ratio (HR) 1⋅42 (95 per cent c.i. 0⋅98 to
Left thoracoabdominal and transhiatal approaches to total gastrectomy
Table 1 Patient characteristics
TH group
(n = 82)
LTA group
(n = 85)
Age (years)* 60 (36–75) 63 (38–75)
Sex ratio (M : F) 71 : 11 63 : 22
Borrmann type
0–2 36 37
3 or 5 46 48
Siewert classification†
Type II 52 43
Type III 27 36
Non-OGJ tumour 3 4
Tumour size (cm)*† 6⋅2 (2⋅5–19) 7⋅0 (2⋅0–18)
cT2 20 20
cT3/4 62 65
pT1b 2 1
pT2a 10 6
pT2b 24 35
pT3 39 37
pT4 7 4
pN0 14 15
0
0·1
No. at risk
TH
LTA
82
85
a Overall survival
72
63
61
52
51
44
47
38
42
31
40
28
37
24
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
1 2 3 4 5
Overallsurvival
6 7
0·6
0·7
0·8
0·9
1·0
survival
344 Y. Kurokawa, M. Sasako, T. Sano, T. Yoshikawa, Y. Iwasaki, A. N
Table 2 Sites of first recurrence
TH group (n = 82) LTA group (n = 85) P*
Lymph nodes 12 (15) 19 (22) 0⋅235
Peritoneum 9 (11) 10 (12) 1⋅000
Liver 8 (10) 9 (11) 1⋅000
Lung 5 (6) 5 (6) 1⋅000
Pleura 3 (4) 1 (1) 0⋅362
Other 5 (6) 2 (2) 0⋅271
Values in parentheses are percentages. TH, transhiatal; LTA, left
thoracoabdominal. *Fisher’s exact test, two-sided.
type. At operation, 141 patients (62 TH, 79
went mediastinal node dissection and 145 (72
had para-aortic node dissection. The rate of
mediastinal nodes was 5 per cent (3 of 62) in th
and 11 per cent (9 of 79) in the LTA group. T
rate in para-aortic nodes was 18 per cent (13
per cent (9 of 73) respectively.
Operative details, including morbidity an
postoperative symptoms and postoperative
function, have been reported previously13,18. M
167 patients
0
0·1
No. at risk
TH
LTA
52
43
a Siewert type II
47
39
41
34
34
29
31
23
26
18
26
16
24
14
20
14
16
10
13
8
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
1 2 3 4 5
Overallsurvival
6 7 8 9 10
TH
LTA
0
0·1
No. at risk
TH
LTA
27
36
b Siewert type III
24
21
19
17
17
15
16
15
16
13
14
12
13
10
11
9
8
8
6
5
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
1 2 3 4 5
Overallsurvival
6 7 8 9 10
Fig. 4 Kaplan–Meier curves of overall survival in patients with a
Siewert type II and b Siewert type III tumours by treatment
group. TH, transhiatal approach; LTA, left thoracoabdominal
63)
app
the
P =
III
44
and
app
the
tho
the
(H
T
10
5 p
par
com
Th
con
per
Dis
Th
con
of t
the
Th
ren
bid
no
app
cor
per
me
len
35% vs 29%
p=0.496
44% vs 22%
p=0.05
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
Y. Kurokawa1
, M. Sasako2
, T. Sano3
, T. Yoshikawa6
, Y. Iwasaki4
, A. Nashimoto7
, S. Ito8
, A. Kurita9
,
J. Mizusawa5
and K. Nakamura5
1Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, 2Department of Surgery, Hyogo College of
Medicine, Nishinomiya, 3Department of Surgery, Cancer Institute Hospital, 4Department of Surgery, Tokyo Metropolitan Cancer and Infectious
Disease Centre, Komagome Hospital and 5
Japan Clinical Oncology Group Data Centre, National Cancer Centre, Tokyo 6
Department of Surgery,
Kanagawa Cancer Centre, Yokohama 7
Department of Surgery, Niigata Cancer Centre Hospital, Niigata 8
Department of Gastroenterological Surgery,
Aichi Cancer Centre Hospital, Nagoya and 9
Department of Surgery, National Hospital Organization Shikoku Cancer Centre, Matsuyama, Japan
Correspondence to: Professor M. Sasako, Department of Surgery, Hyogo College of Medicine, 1–1, Mukogawa-cho, Nishinomiya, Hyogo 663–8501, Japan
(e-mail: msasako@hyo-med.ac.jp)
Background: The optimal surgical approach for treatment of oesophagogastric junction (OGJ) cancer
is controversial. A randomized clinical trial (JCOG9502) comparing transhiatal (TH) and left thoraco-
abdominal (LTA) approaches was stopped after the first interim analysis owing to limited efficacy for
LTA resections. Complete 10-year follow-up data are now available.
Methods: Patients with histologically proven adenocarcinoma of the OGJ or gastric cardia with
oesophageal invasion of 3 cm or less were randomized to a TH or LTA approach. Both groups underwent
total gastrectomy and splenectomy with D2 nodal dissection plus para-aortic lymphadenectomy above
the left renal vein. For LTA, a thorough mediastinal lymphadenectomy below the left inferior pulmonary
vein was also mandatory. The primary endpoint was overall survival.
Results: A total of 167 patients (82 TH, 85 LTA) were enrolled. The 10-year overall survival rate was
37 (95 per cent c.i. 26 to 47) per cent for the TH approach and 24 (15 to 34) per cent for the LTA
technique (P = 0⋅060). The hazard ratio for death was 1⋅42 (0⋅98 to 2⋅05) for the LTA technique. Subgroup
analysis based on the Siewert classification indicated non-significant survival advantages in favour of the
TH approach.
Conclusion: LTA resections should be avoided in the treatment of adenocarcinoma of the OGJ or gastric
cardia. Registration number: NCT00149266 (https://www.clinicaltrials.gov).
Paper accepted 4 December 2014
Published online 21 January 2015 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9764
Introduction
The incidence of adenocarcinoma of the oesophago-
gastric junction (OGJ) has increased in developed countries
over the past 20 years1,2
. Although surgery is considered
essential as part of a curative treatment strategy for most
patients, survival remains poor even in those who undergo
R0 resection, with or without additional therapy3. To
improve the R0 resection rate and long-term outcomes,
extended surgery with en bloc lymphadenectomy has been
attempted for many years. When considering tumours
arising from the cardia (Siewert type III4), or those at the
OGJ (Siewert type II) with minimal oesophageal extension
where total gastrectomy seems appropriate, left thoraco-
abdominal (LTA) and transhiatal (TH) approaches have
been advocated for curative resection. There is no clear
information to indicate whether the operative approach
influences long-term outcome.
In East Asian countries, including Japan, the majority of
OGJ tumours are Siewert types II and III5. The incidence
of lower mediastinal lymph node metastasis from type
II and III tumours is reported to range from 10 to 40
per cent6–12. Some institutions prefer the LTA to the
TH approach in order to perform lymph node dissection
in the lower mediastinal field and obtain a safe surgical
margin6,7, whereas others prefer the TH technique owing
© 2015 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
Table 1 Patient characteristics
TH group
(n = 82)
LTA group
(n = 85)
Age (years)* 60 (36–75) 63 (38–75)
Sex ratio (M : F) 71 : 11 63 : 22
Borrmann type
0–2 36 37
3 or 5 46 48
Siewert classification†
Type II 52 43
Type III 27 36
Non-OGJ tumour 3 4
Tumour size (cm)*† 6⋅2 (2⋅5–19) 7⋅0 (2⋅0–18)
cT2 20 20
cT3/4 62 65
pT1b 2 1
pT2a 10 6
pT2b 24 35
pT3 39 37
pT4 7 4
pN0 14 15
pN1 24 27
pN2 30 25
pN3/4 14 16
pN0 14 15
0
0·1
No. at risk
TH
LTA
82
85
a Overall survival
72
63
61
52
51
44
47
38
42
31
40
28
37
24
0·2
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1 0
1 2 3 4 5
Overallsurvival
6 7
0·3
0·4
0·5
0·6
0·7
0·8
0·9
1·0
“Left thoraco-abdominal resections should be avoided in the treatment of adenocarcinoma
of the esophago-gastric junction or gastric cardia. “©2015 Marco Lotti – mlotti@hpg23.it

The Meta-Analyses

Figure 2. Forest plot of 5-year overall survival rates for RCTs and non-RCTs. a: RCTs; b: non-RCTs. The 95% confidence interval (CI) for the
hazard ratio for each study is represented by a horizontal line and the point estimate is represented by a square. The size of the square corresponds
to the weight of the study in the meta-analysis. The 95% CI for pooled estimates is represented by a diamond. Data for a fixed-effects model are
shown as there was no statistical heterogeneity. df = degrees of freedom; I2
= percentage of the total variation across studies due to heterogeneity;
IV = Inverse Variance; SE = standard error; Z = test of overall treatment effect.
doi:10.1371/journal.pone.0037698.g002
Transthoracic Resection for GEJ Cancers
Transthoracic Resection versus Non-Transthoracic
Resection for Gastroesophageal Junction Cancer: A
Meta-Analysis
Kun Yang1.
, Hai-Ning Chen2.
, Xin-Zu Chen1
, Qing-Chun Lu2
, Lin Pan2
, Jie Liu1
, Bin Dai1
, Bo Zhang1
*, Zhi-
Xin Chen1
, Jia-Ping Chen1
, Jian-Kun Hu1
1 Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China, 2 West China School of
Medicine, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China
Abstract
Background: The aim of this meta-analysis is to evaluate the impact of transthoracic resection on long-term survival of
patients with GEJ cancer and to compare the postoperative morbidity and mortality of patients undergoing transthoracic
resection with those of patients who were not undergoing transthoracic resection.
Method: Searches of electronic databases identifying studies from Medline, Cochrane Library trials register, and WHO Trial
Registration etc were performed. Outcome measures were survival, postoperative morbidity and mortality, and operation
related events.
Results: Twelve studies (including 5 RCTs and 7 non-RCTs) comprising 1105 patients were included in this meta-analysis,
with 591 patients assigned treatment with transthoracic resection. Transthoracic resection did not increase the 5-y overall
survival rate for RCTs and non-RCTs (HR = 1.01, 95% CI 0.80- 1.29 and HR = 0.89, 95% CI 0.70- 1.14, respectively). Stratified by
the Siewert classification, our result showed no obvious differences were observed between the group with transthoracic
resection and group without transthoracic resection (P.0.05). The postoperative morbidity (RR = 0.69, 95% CI 0.48- 1.00 and
OR = 0.55, 95% CI 0.25- 1.22) and mortality (RD = 20.03, 95% CI 20.06- 0.00 and RD = 0.00, 95% CI 20.05- 0.05) of RCTs and
non-RCTs did not suggest any significant differences between the two groups. Hospital stay was long with thransthoracic
resection (WMD = 25.80, 95% CI 210.38- 21.23) but did not seem to differ in number of harvested lymph nodes, operation
time, blood loss, numbers of patients needing transfusion, and reoperation rate. The results of sensitivity analyses were
similar to the primary analyses.
Conclusions: There were no significant differences of survival rate and postoperative morbidity and mortality between
transthoracic resection group and non-transthoracic resection group. Both surgical approaches are acceptable, and that one
offers no clear advantage over the other. However, the results should be interpreted cautiously since the qualities of
included studies were suboptimal.
Citation: Yang K, Chen H-N, Chen X-Z, Lu Q-C, Pan L, et al. (2012) Transthoracic Resection versus Non-Transthoracic Resection for Gastroesophageal Junction
Cancer: A Meta-Analysis. PLoS ONE 7(6): e37698. doi:10.1371/journal.pone.0037698
Editor: Robert S. Phillips, University of York, United Kingdom
Received July 14, 2011; Accepted April 25, 2012; Published June 4, 2012
Copyright: ß 2012 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by Projects (2008SZ0168) in the Science & Technology Pillar Program, Scientific and Technological Department of Sichuan
Province, People’s Republic of China( http://www.scst.gov.cn/info/) and a grant from National Natural Science Foundation of China (No.81071777). (http://www.
nsfc.org.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: zhangbo7310@126.com
. These authors contributed equally to this work.
Introduction
Gastroesophageal junction (GEJ) cancer has been gradually
considered as an entity separate from both esophageal cancer and
gastric cancer [1]. Although a decline in incidence of gastric
carcinoma, there has been a tendency of proximal migration of
carcinoma in Western countries [2–4]. A kind of classification
proposed by Siewert & Stein, which includes three types, was
widely accepted for GEJ cancer [5]. According to the classifica-
tion, type 1 is defined as tumors whose centers are located 1 to
5 cm above the gastroesophageal junction (distal esophageal
adenocarcinoma); type 2, adenocarcinoma with its epicenter
located between 1 cm proximal and 2 cm distal of the GEJ, is
defined as a true cardia carcinoma; and the center of the type 3
tumor lies 2 to 5 cm distal to the GEJ (subcardial gastric
carcinoma) [5].
Surgery is the mainstay treatment although the prognosis is
poor. Controversies, especially on operation route, still exist. The
debate on the question whether transthoracic (TT) resection or
non- transthoracic resection is better for GEJ cancer remains
continuing. Transthoracic resection was advocated with intent to
prolong the survival, because mediastinal lymph nodes could be
observed and dissected under the direct vision and a safe surgical
PLoS ONE | www.plosone.org 1 June 2007 | Volume 7 | Issue 6 | e37698
There were no significant
differences of survival rate
and postoperative
morbidity and mortality
between transthoracic
resection group and non-
transthoracic resection
group.
Both surgical approaches
are acceptable, and no one
offers clear advantage over
the other.
However, the results
should be interpreted
cautiously since the
qualities of included
studies were suboptimal.

Study or subgroup log(hazard ratio) SE Weight Hazard ratio Hazard ratio
IV, random, 95%CI IV, random, 95%CI
Nakamura 2008 0.49 0.24 23.4% 1.63 (1.02, 2.61)
Omloo 2007 -0.03 0.19 28.7% 0.97 (0.67, 1.41)
Sasako 2006 0.3 0.24 23.4% 1.35 (0.84, 2.16)
Zheng 2010 -0.28 0.23 24.4% 0.76 (0.48, 1.19)
Total (95%CI) 100.0% 1.11 (0.81, 1.54)
Heterogeneity: Tau
2
= 0.06; χ2
= 6.53, df = 3 (P = 0.09); I2
= 54%
Test for overall effect: Z = 0.65 (P = 0.51)
0.01 0.1 1 1.0 100
Favours transthoracic Favours transhiatal
IV, fixed, 95%CI IV, fixed, 95%CI
Omloo 2007 -0.05 0.32 100.0% 0.95 (0.51, 1.78)
Total (95%CI) 100.0% 0.95 (0.51, 1.78)
Heterogeneity: Not applicable
0.01 0.1 1 1.0 100
Nakamura 2008 0.62 0.44 16.0% 1.86 (0.78, 4.40)
Omloo 2007 -0.06 0.24 53.8% 0.94 (0.59, 1.51)
Sasako 2006 0.17 0.32 30.2% 1.19 (0.63, 2.22)
Total (95%CI) 100.0% 1.13 (0.80, 1.59)
Heterogeneity: χ2
= 1.88, df = 2 (P = 0.39); I2
= 0%
0.01 0.1 1 1.0 100
Nakamura 2008 0.54 0.59 28.2% 1.72 (0.54, 5.45)
Sasako 2006 0.5 0.37 71.8% 1.65 (0.80, 3.40)
Total (95%CI) 100.0% 1.67 (0.90, 3.08)
Heterogeneity: χ2
= 0.00, df = 1 (P = 0.95); I2
= 0%
0.01 0.1 1 1.0 100
Figure 5 Forest plot of overall survival in the transthoracic group vs transhiatal group of cancers of the esophagogastric junction. A: All Siewert types; B:
SiewertⅠ; C: Siewert Ⅱ; D: Siewert Ⅲ. IV: Inverse variance.
Wei MT et al. TT vs TH for esophagogastric cancer
A
B
C
D
Transthoracic vs transhiatal surgery for cancer of the
esophagogastric junction: A meta-analysis
Ming-Tian Wei, Yuan-Chuan Zhang, Xiang-Bing Deng, Ting-Han Yang, Ya-Zhou He, Zi-Qiang Wang
Ming-Tian Wei, Yuan-Chuan Zhang, Xiang-Bing Deng, Ting-
Han Yang, Ya-Zhou He, Zi-Qiang Wang, Department of Gas-
trointestinal Surgery, West China Hospital, Sichuan University,
Chengdu 610041, Sichuan Province, China
Author contributions: Wei MT and Wang ZQ designed the
research; Wang ZQ provided supervision; Wei MT and He YZ
performed the research; Deng XB and Yang TH performed a
literature search and collected the data; Wei MT and Zhang YC
analyzed the data and wrote the paper.
Supported by National Natural Science Foundation of China,
No. 81172373
Correspondence to: Zi-Qiang Wang, Professor, Department
of Gastrointestinal Surgery, West China Hospital, Sichuan Uni-
versity, No. 37 Guo Xue Alley, Chengdu 610041, Sichuan Prov-
ince, China. wangzqzyh@163.com
Telephone: +86-28-85422480 Fax: +86-28-81654035
Received: November 20, 2013 Revised: February 13, 2014
Accepted: March 5, 2014
Published online: August 7, 2014
Abstract
AIM: To compare the efficacy and safety of the trans-
thoracic and transhiatal approaches for cancer of the
esophagogastric junction.
METHODS: An electronic and manual search of the
literature was conducted in PubMed, EmBase and the
Cochrane Library for articles published between March
1998 and January 2013. The pooled data included the
following parameters: duration of surgical time, blood
loss, dissected lymph nodes, hospital stay time, anasto-
motic leakage, pulmonary complications, cardiovascular
complications, 30-d hospital mortality, and long-term
survival. Sensitivity analysis was performed by exclud-
ing single studies.
RESULTS: Eight studies including 1155 patients with
cancer of the esophagogastric junction, with 639 pa-
tients in the transthoracic group and 516 in the tran-
shiatal group, were pooled for this study. There were
no significant differences between two groups concern-
ing surgical time, blood loss, anastomotic leakage, or
cardiovascular complications. Dissected lymph nodes
also showed no significant differences between two
groups in randomized controlled trials (RCTs) and non-
RCTs. However, we did observe a shorter hospital stay
(WMD = 1.92, 95%CI: 1.63-2.22, P < 0.00001), lower
30-d hospital mortality (OR = 3.21, 95%CI: 1.13-9.12,
P = 0.03), and decreased pulmonary complications (OR
= 2.95, 95%CI: 1.95-4.45, P < 0.00001) in the tran-
shiatal group. For overall survival, a potential survival
benefit was achieved for type Ⅲ tumors with the tran-
shiatal approach.
CONCLUSION: The transhiatal approach for cancers
of the esophagogastric junction, especially types Ⅲ,
should be recommended, and its long-term outcome
benefits should be further evaluated.
© 2014 Baishideng Publishing Group Inc. All rights reserved.
Key words: Transthoracic surgery; Transhiatal surgery;
Cancer of the esophagogastric junction; Meta-analysis
Core tip: Surgical resection is the optimum therapy
for cancer of the esophagogastric junction, and the
transthoracic and transhiatal approaches are the two
major surgical approaches used worldwide. However,
considerable debate exists on the superior benefits of
the two approaches regarding their efficacy and safety.
We conducted this meta-analysis to address the issue.
The results indicated a shorter hospital stay, lower 30-d
hospital mortality and decreased pulmonary complica-
tions with the transhiatal approach compared with the
transthoracic approach. Moreover, a potential survival
benefit was achieved for type Ⅲ tumors using the tran-
shiatal approach.
Wei MT, Zhang YC, Deng XB, Yang TH, He YZ, Wang ZQ.
Transthoracic vs transhiatal surgery for cancer of the esophago-
Transthoracic vs transhiatal surgery for cancer of the
esophagogastric junction: A meta-analysis
Ming-Tian Wei, Yuan-Chuan Zhang, Xiang-Bing Deng, Ting-Han Yang, Ya-Zhou He, Zi-Qiang Wang
Ming-Tian Wei, Yuan-Chuan Zhang, Xiang-Bing Deng, Ting-
Han Yang, Ya-Zhou He, Zi-Qiang Wang, Department of Gas-
trointestinal Surgery, West China Hospital, Sichuan University,
Chengdu 610041, Sichuan Province, China
Author contributions: Wei MT and Wang ZQ designed the
research; Wang ZQ provided supervision; Wei MT and He YZ
performed the research; Deng XB and Yang TH performed a
literature search and collected the data; Wei MT and Zhang YC
analyzed the data and wrote the paper.
Supported by National Natural Science Foundation of China,
No. 81172373
Correspondence to: Zi-Qiang Wang, Professor, Department
of Gastrointestinal Surgery, West China Hospital, Sichuan Uni-
versity, No. 37 Guo Xue Alley, Chengdu 610041, Sichuan Prov-
ince, China. wangzqzyh@163.com
Telephone: +86-28-85422480 Fax: +86-28-81654035
Received: November 20, 2013 Revised: February 13, 2014
Accepted: March 5, 2014
Published online: August 7, 2014
Abstract
AIM: To compare the efficacy and safety of the trans-
thoracic and transhiatal approaches for cancer of the
esophagogastric junction.
METHODS: An electronic and manual search of the
literature was conducted in PubMed, EmBase and the
Cochrane Library for articles published between March
1998 and January 2013. The pooled data included the
following parameters: duration of surgical time, blood
loss, dissected lymph nodes, hospital stay time, anasto-
motic leakage, pulmonary complications, cardiovascular
complications, 30-d hospital mortality, and long-term
survival. Sensitivity analysis was performed by exclud-
ing single studies.
RESULTS: Eight studies including 1155 patients with
cancer of the esophagogastric junction, with 639 pa-
tients in the transthoracic group and 516 in the tran-
shiatal group, were pooled for this study. There were
no significant differences between two groups concern-
ing surgical time, blood loss, anastomotic leakage, or
cardiovascular complications. Dissected lymph nodes
also showed no significant differences between two
groups in randomized controlled trials (RCTs) and non-
RCTs. However, we did observe a shorter hospital stay
(WMD = 1.92, 95%CI: 1.63-2.22, P < 0.00001), lower
30-d hospital mortality (OR = 3.21, 95%CI: 1.13-9.12,
P = 0.03), and decreased pulmonary complications (OR
= 2.95, 95%CI: 1.95-4.45, P < 0.00001) in the tran-
shiatal group. For overall survival, a potential survival
benefit was achieved for type Ⅲ tumors with the tran-
shiatal approach.
CONCLUSION: The transhiatal approach for cancers
of the esophagogastric junction, especially types Ⅲ,
should be recommended, and its long-term outcome
benefits should be further evaluated.
Key words: Transthoracic surgery; Transhiatal surgery;
Cancer of the esophagogastric junction; Meta-analysis
Core tip: Surgical resection is the optimum therapy
for cancer of the esophagogastric junction, and the
transthoracic and transhiatal approaches are the two
major surgical approaches used worldwide. However,
considerable debate exists on the superior benefits of
the two approaches regarding their efficacy and safety.
We conducted this meta-analysis to address the issue.
The results indicated a shorter hospital stay, lower 30-d
hospital mortality and decreased pulmonary complica-
tions with the transhiatal approach compared with the
transthoracic approach. Moreover, a potential survival
benefit was achieved for type Ⅲ tumors using the tran-
shiatal approach.
Wei MT, Zhang YC, Deng XB, Yang TH, He YZ, Wang ZQ.
Transthoracic vs transhiatal surgery for cancer of the esophago-
META-ANALYSIS
Submit a Manuscript: http://www.wjgnet.com/esps/
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx
DOI: 10.3748/wjg.v20.i29.10183
10183 August 7, 2014|Volume 20|Issue 29|WJG|www.wjgnet.com
World J Gastroenterol 2014 August 7; 20(29): 10183-10192
ISSN 1007-9327 (print) ISSN 2219-2840 (online)
For overall survival, no
significance was found
in either all Siewert’ s
types or single
Siewert’s type.
A potential survival
benefit was achieved
for type III tumors
using the transhiatal
approach compared
with the transthoracic
approach.
We conclude that, for
cancers of the
esophagogastric
junction (especially for
Siewert’s type III
tumors) the transhiatal
approach should be
recommended as the
optimal choice.

Lotti Marco MD - Cancer of the Oesophago-Gastric Junction

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