Surgery xxx (2021) 1e9
Contents lists available at ScienceDirect
Surgery
journal homepage: www.elsevier.com/locate/surg
Evolution of gastrectomy for cancer over 30-years: Changes in
presentation, management, and outcomes
S. Michael Griffin, OBE, MD, PRCSEda, Sivesh K. Kamarajah, BMedSci, MBChBa,b,
Maziar Navidi, MB, ChB, FRCSEda, Shajahan Wahed, MD, FRCSEnga,
Arul Immanuel, MD, FRCSEda, Nick Hayes, FRCSEnga,
Alexander W. Phillips, MD, MA, FRCSEda,c,*
a
Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle-Upon-Tyne, UK
Institute of Cellular Medicine, Newcastle University, Newcastle-Upon-Tyne, UK
c
School of Medical Education, Newcastle University, Newcastle upon Tyne
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Accepted 25 January 2021
Available online xxx
Background: Gastric cancer has seen a considerable change in management, and outcomes for the past
30 years. Historically, the overall prognosis has been regarded as poor. However, the use of multimodal
treatment, and integration of enhanced recovery pathways have improved short and long-term outcomes. The aim of this study was to evaluate the changing trends in presentation, management, and
outcomes for patients undergoing surgical treatment for gastric cancers over 30 years.
Methods: Data from consecutive patients undergoing gastrectomy with curative intent for gastric
adenocarcinoma between 1989 and 2018 from a single-center, high-volume unit were reviewed. Presentation method, management strategies and outcomes were reviewed. Patients were grouped into
successive 5-year cohorts for comparison and evaluation of changing trends.
Results: Between 1989 and 2018, 1,162 patients underwent gastrectomy with curative intent for cancer.
Median age was 71 years (interquartile range, 6376 years) and 763 (66%) were male. Patient presentation changed with epigastric discomfort now the most common presentation (67%). An improvement
in overall complications from 54% to 35% (P ¼ .006) and mortality from 8% to 1% (P < .001) was seen over
the time period and overall survival improved from 28 months to 53 months (P < .001).
Conclusion: Both short-term and long-term outcomes have significantly improved over the 30 years
studied. The reasons for this are multifactorial and include the use of perioperative chemotherapy, the
introduction of an enhanced recovery pathway, and improved preoperative assessment of patients
through a multidisciplinary input.
© 2021 Elsevier Inc. All rights reserved.
Introduction
Gastric cancer is the third leading cause of cancer death and the
fifth most common cancer in the world.1 Worldwide, approximately 1 million new cases of gastric cancer are diagnosed annually.2 The 5-year overall survival for resectable gastric cancer is
approximately 20% to 30% worldwide. However, a survival of 70%
S.M. Griffin and S.K. Kamarajah contributed equally.
* Reprint requests: Alexander W. Phillips, MD, MA, FRCSEd, Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle University Trust Hospitals,
Newcastle-Upon-Tyne, UK.
E-mail address: awphillips@doctors.net.uk (A.W. Phillips);
Twitter: @smgriffin3, @sivesh93, @Maz_surgery, @ArulImmanuel,
@AlexWPhillips7
https://doi.org/10.1016/j.surg.2021.01.040
0039-6060/© 2021 Elsevier Inc. All rights reserved.
has been achieved in Japan and in other Eastern countries, where
the high incidence of the disease is managed with screening programs to find tumors at an earlier stage, and patients receive radical
surgery at high-volume centers.3
Throughout the past 2 decades, there have been significant
changes in the management of patients with gastric cancers. Neoadjuvant treatment is increasingly used and in some countries is
now regarded as the gold standard for those with locally advanced
disease.3,4 A standardized surgical dissection and the adherence to
oncological principles even when using minimally invasive techniques are important in obtaining good survival rates.5e8 There is
also an increasing appreciation of improving the whole patient
pathway involving prehabilitation before surgery and enhanced
recovery pathways in the immediate postoperative setting.9 Understanding the impact of interventions and identifying areas
2
S.M. Griffin et al. / Surgery xxx (2021) 1e9
where little progress has been made is key to determining which
components of treatment need further targeting to try and improve
outcomes.
This study evaluates outcomes after gastric resection for the past
30 years in a single high-volume UK center. Key changes in management strategy and their potential impact have been highlighted,
along with areas where little progress has been made. The aim was
to help identify which potential areas may lend themselves to
further improvement and identify areas of research to target to help
enhance outcomes.
reconstruction, in a retro-colic fashion. A 45 cm roux limb is created
with a 2 layered continuous jejunal-jejunal anastomosis.
A subtotal gastrectomy with D2 lymphadenectomy is carried out
in a similar fashion. However, the stomach is transected with a
stapling devise, leaving a small remnant based on 2 to 3 short
gastric vessels. The Roux limbs is prepared as above and an end-toside gastro-jejunostomy is fashioned as a Hoffmeister valve with a
handsewn, 2 layered anastomosis.
Methods
Consecutive patients treated for adenocarcinoma of the stomach
between January 1989 and December 2018 from the Northern
Oesophagogastric Unit, Newcastle upon Tyne were included. Patients were discussed at a multidisciplinary meeting and subsequently received neoadjuvant chemotherapy followed by surgery
(either total gastrectomy or subtotal gastrectomy) or had surgery as
their initial curative management. Patients were identified from a
contemporaneously maintained database.
Histopathological reporting was carried out by specialist
gastrointestinal pathologists using a standardized proforma. This
was in line with guidelines produced by the Royal College of Pathologists, which included tumor type and differentiation, depth of
tumor infiltration, and tumor regression.12,13 The total number of
nodes from each location and nodal metastases were recorded
along with the presence of extracapsular, lymphatic, and venous
and perineural invasion. Lymph node groups were dissected from
the specimen by the operating surgeon and analyzed separately by
the pathologist.14 The pathological stage was determined using the
American Joint Committee on Cancer eighth edition TNM staging
system, which was retrospectively applied to earlier specimens.15
Pretreatment staging
Follow-up and definition of recurrence
All patients were staged according to standardized protocols
which include endoscopy with biopsy specimen, and a thoracoabdominal computed tomography scan. During the timeframe
of this study positron emission tomography/computed tomography
scan evolved to be a necessary component for patients being
considered for radical (curative) treatment and endoscopic ultrasonography was used selectively. Staging laparoscopy with washings for cytology was used in potential cases of locally advanced
disease. In patients with histology proven, locally advanced malignancy, that was resectable, without metastases (cT1Nþ or
cT3þN0-3) perioperative chemotherapy followed by surgery was
the main treatment option after the integration of Medical
Research Council Adjuvant Gastric Infusional Chemotherapy
(MAGIC) study.10 Patients with a histology other than adenocarcinoma and those with metastatic disease at the time of the operation were excluded.
Patients were followed up until death or for 10 years. Patients
were seen at 3 to 6 monthly intervals in the first 2 years, 6 monthly
for 2 years, and then annually. Recurrence of disease was based on
clinical grounds and confirmed endoscopically or radiologically.
The minimum follow-up used for long-term survival was 36
months.
Patient population
Pathology and staging
Complications
Multiple neoadjuvant regimens were used in the present study
determined by the standard of care and recruiting clinical trials at
the time of treatment with patients treated earlier in the time
period having unimodality surgery. However, the majority of patients with locally advanced cancer received chemotherapy as per
the MAGIC regime. Total gastrectomy or subtotal gastrectomy with
D2 lymph node dissection was performed within 4 to 8 weeks after
completion of the neoadjuvant therapy using an open approach.
Complications were recorded contemporaneously. Presence of
complications was defined as has been done previously.16 As well as
recording the occurrence of complications they were also classified
according to severity using the Accordion17 and Clavien-Dindo
scores.18 Statistical analysis
Categorical variables were compared using the c2 test. Nonnormally distributed data were analyzed using the Mann-Whitney
U test. Survival was estimated using Kaplan-Meier survival curves
and compared using the log-rank test. Multivariable analyses used
Cox proportional hazards models. Comparison of outcomes between 5-year periods (1989e1993, 1994e1998, 1999e2003,
2004e2008, 2009e2013, 2014e2018) was also performed,
although for long survival patients were only analyzed up to 2017 to
provide a minimum 36 months follow-up for survivors. Data
analysis were performed using R Foundation Statistical software (R
3.2.2) with TableOne, ggplot2, Hmisc, Matchit, and survival packages (R Foundation for Statistical Computing, Vienna, Austria), as
previously reported.19
Surgical technique
Results
Resections were carried out using a standardized open approach
with a radical en bloc D2 lymphadenectomy.11 Proximal tumors and
patients diagnosed with linitis plastica were treated with a total
gastrectomy. Patients with a distal tumor where adequate clearance (>5 cm) could be achieved received a subtotal gastrectomy. A
standardized approach was used throughout the time period with a
bursectomy where possible, and en bloc lymph node dissection. For
total gastrectomy, an esophageal-jejunal anastomosis was
routinely formed using a circular stapler with a roux-en-Y
Baseline demographics
Treatment
Between 1989 and 2018, 1,162 patients underwent gastrectomy for gastric cancer. Median age of the entire cohort was
71 years (interquartile range, 6376 years) and 763 (66%)
patients were male. Overall median survival for the entire
cohort was 32 months (interquartile range, 1477 months).
The majority of patients underwent subtotal gastrectomy (54%,
n ¼ 623 patients).
S.M. Griffin et al. / Surgery xxx (2021) 1e9
3
Table I
Baseline demographics and trends in patient presentation
n
Age presentation (median [IQR])
Sex, male (%)
BMI (median [IQR])
Smoking status (%)
Current
Ex-smoker
Never
Unknown
Alcohol status (%)
Current
Ex-drinker
Never
Unknown
ASA grade (%)
Grade 1
Grade 2
Grade 3
Grade 4
Unknown
Clinical presentation
Weight loss (%)
Anorexia (%)
Vomiting/regurgitation (%)
Epigastric discomfort (%)
Epigastric pain (%)
Retrosternal pain (%)
Dysphagia (%)
Unknown
Can eat normally
Difficulty with solids
Liquids only
Soft or liquid food only
Total dysphagia
Odynophagia (%)
Nausea (%)
Jaundice (%)
Hepatomegaly (%)
Anemia (%)
Reflux (%)
Overall
19891993
19941998
19952003
20042008
20092013
20142018
1162
71 [63e76]
763 (66)
25 [23e28]
24
68 [58e73]
20 (83)
25 [23e27]
120
69 [64e74]
86 (72)
23 [21e26]
203
69 [62e75]
137 (67)
24 [22e27]
276
71 [63e76]
188 (68)
25 [23e29]
287
71 [63e77]
178 (62)
25 [23e29]
252
72 [64e78]
154 (61)
26 [24e29]
264 (23)
496 (43)
378 (33)
24 (2)
9
7
8
0
(38)
(29)
(33)
(0)
40 (33)
47 (39)
32 (27)
1 (1)
44
77
71
11
64 (23)
137 (50)
70 (25)
5 (2)
56 (20)
126 (44)
102 (36)
3 (1)
51 (20)
102 (40)
95 (38)
4 (2)
692 (60)
61 (5)
376 (32)
33 (3)
17 (71)
1 (4)
6 (25)
0 (0)
54 (45)
6 (5)
44 (37)
16 (13)
121 (60)
6 (3)
60 (30)
16 (8)
173 (63)
20 (7)
83 (30)
0 (0)
171 (60)
21 (7)
94 (33)
1 (0)
156 (62)
7 (3)
89 (35)
0 (0)
82 (7)
513 (44)
404 (35)
14 (1)
149 (13)
1 (4)
6 (25)
3 (12)
0 (0)
14 (58)
12 (10)
31 (26)
19 (16)
2 (2)
56 (47)
21 (10)
63 (31)
59 (29)
2 (1)
58 (29)
19 (7)
138 (50)
100 (36)
4 (1)
15 (5)
26 (9)
155 (54)
97 (34)
5 (2)
4 (1)
3 (1)
120 (48)
126 (50)
1 (0)
2 (1)
598
203
346
464
378
131
(51)
(17)
(30)
(40)
(33)
(11)
17 (71)
10 (42)
9 (38)
3 (12)
14 (58)
3 (12)
79 (66)
47 (39)
51 (42)
8 (7)
75 (62)
14 (12)
110 (54)
53 (26)
58 (29)
76 (37)
86 (42)
34 (17)
133 (48)
58 (21)
63 (23)
110 (40)
65 (24)
23 (8)
146 (51)
22 (8)
96 (33)
99 (34)
69 (24)
37 (13)
113 (45)
13 (5)
69 (27)
168 (67)
69 (27)
20 (8)
32 (3)
877 (75)
149 (13)
23 (2)
71 (6)
10 (1)
37 (3)
222 (19)
4 (0)
4 (0)
322 (28)
248 (21)
0 (0)
16 (67)
4 (17)
1 (4)
3 (12)
0 (0)
2 (8)
6 (25)
0 (0)
0 (0)
4 (17)
3 (12)
0 (0)
79 (66)
25 (21)
4 (3)
10 (8)
2 (2)
11 (9)
38 (32)
0 (0)
0 (0)
41 (34)
39 (32)
3 (1)
158 (78)
26 (13)
4 (2)
10 (5)
2 (1)
8 (4)
48 (24)
0 (0)
3 (1)
51 (25)
47 (23)
15 (5)
228 (83)
21 (8)
3 (1)
8 (3)
1 (0)
4 (1)
48 (17)
0 (0)
1 (0)
75 (27)
50 (18)
11 (4)
211 (74)
36 (13)
4 (1)
23 (8)
2 (1)
6 (2)
53 (18)
4 (1)
0 (0)
70 (24)
60 (21)
3 (1)
185 (73)
37 (15)
7 (3)
17 (7)
3 (1)
6 (2)
29 (12)
0 (0)
0 (0)
81 (32)
49 (19)
(22)
(38)
(35)
(5)
P value
.01
.068
<.001
.001
<.001
<.001
.001
<.001
.002
<.001
<.001
.034
.003
.001
<.001
.032
.076
.12
.026
BMI, body mass index; IQR, interquartile range.
Patient presentation
During this 30-year time period, there was an increase in the
number of patients undergoing gastrectomy in each 5-year
period (Table I). During the study period presenting symptoms
changed with a significant fall in the number of patients presenting with weight loss, from 71% in the initial time period to
45% (P ¼ .001) in the final time period, this correlated with a
small increase in body mass index (BMI) of patients at presentation from 25 kg/m2 to 26 kg/m2 (P < .001) and fewer patients
presenting with anorexia, from 42% in the early time cohort to
5% (P < .001; Table I). The most common presentation for patients in the most recent cohort was epigastric discomfort which
67% stated as a symptom, compared with 7% to 12% in the
earliest 2 cohorts (P < .001). Patient presentation with regurgitation and odynophagia fell steadily over the years studied from
38% to 27% (P ¼ .002) and 8% to 2% (P ¼ .001).
Changes in stage at presentation and surgery
Those that underwent surgery were increasingly at a more
advanced clinical stage (stage III) with 11% of patients in the earlier
cohort having stage III disease, compared with 56% in the final
cohort (P < .001; Table II). There was a significant change in the
surgery performed with more than 70% of patients in the early
cohort undergoing a total gastrectomy compared with approximately 40% in the latter years.
Changes in pathology
Median lymph node yield was significantly less in the first 2
cohorts (19e25 nodes, respectively) compared with the last cohorts
(28e35 nodes, P < .001), longitudinal R1 resection rates were
significantly reduced from 21% to 6% (P ¼ .002).
Patient outcomes
Overall survival improved more than the 30 years studied (Fig 1,
A and B). Median survival increased between each cohort from 28.3
months in the first cohort, to 53 months final cohort (P < .001).
Overall, there was a steady improvement in survival by stage in
each time period (Fig 2, AC).
Postoperative complications are presented in Table II. The
overall complication rates were 42%, with a significant decrease
from 54% to 35% (P ¼ .006). There was also a significant decrease in
rates of major complications from 16% to 4% (P < .001). The most
common complications were pulmonary complications followed by
cardiac complications, surgical site infections, and anastomotic
leaks. There was a significant decrease in pulmonary and cardiac
complications. This was accompanied by a fall in in-patient and
4
S.M. Griffin et al. / Surgery xxx (2021) 1e9
Table II
Trends in operative management and pathological assessment
n
Total gastrectomy (%)
Overall treatment (%)
Neoadjuvant chemotherapy þ surgery
Surgery only
Overall pathological stage (%)
Stage 0
Stage IA
Stage IB
Stage IIA
Stage IIB
Stage IIIA
Stage IIIB
Unknown
Pathological outcomes
Tumor grade (%)
Moderate
Poor
Unknown
LN examined (median [IQR])
LN positive (median [IQR])
Margin status R1 (%)
Lymph involvement (%)
Venous involvement (%)
Perieneural involvement (%)
Extracapsular spread ¼ yes (%)
Postoperative outcomes
Critical care stay (median [IQR])
Duration of stay (median [IQR])
Overall complications ¼ Yes (%)
None
Clavien-Dindo grade 1/2
Clavien-Dindo grade 35
Superficial infection (%)
Pulmonary complications
Cardiac complications
Anastomotic leaks
In hospital mortality (%)
30-day mortality
Overall
1989e1993
1994e1998
1995e2003
2004e2008
2009e2013
2014e2018
1162
539 (46)
24
17 (71)
120
89 (74)
203
113 (56)
276
107 (39)
287
110 (38)
252
103 (41)
294 (25)
868 (75)
0 (0)
24 (100)
0 (0)
120 (100)
2 (1)
201 (99)
59 (21)
217 (79)
114 (40)
173 (60)
119 (47)
133 (52)
36 (3)
205 (18)
181 (16)
200 (17)
193 (17)
150 (13)
93 (8)
104 (9)
1
3
1
4
4
6
1
4
3 (3)
10 (8)
15 (13)
14 (12)
28 (23)
19 (16)
8 (7)
23 (19)
3 (2)
28 (14)
31 (15)
31 (15)
41 (20)
26 (13)
8 (4)
35 (17)
4 (1)
64 (23)
55 (20)
60 (22)
46 (17)
28 (10)
11 (4)
8 (3)
5 (2)
50 (17)
47 (16)
50 (17)
40 (14)
39 (14)
39 (14)
17 (6)
20
50
32
41
34
32
26
17
477 (44)
528 (49)
67 (6)
28 [20e38]
1 [0e6]
89 (8)
631 (54)
469 (40)
556 (48)
173 (15)
6 (27)
12 (55)
4 (18)
25 [16e30]
4 [1e9]
5 (21)
11 (46)
6 (25)
4 (17)
0 (0)
47 (43)
58 (53)
5 (5)
19 [13e29]
4 [0e9]
17 (14)
59 (49)
33 (28)
57 (48)
0 (0)
83 (47)
87 (50)
5 (3)
25 [19e36]
3 [0e7]
20 (10)
124 (61)
87 (43)
116 (57)
1 (0)
110 (45)
117 (48)
18 (7)
29 [22e40]
1 [0e6]
13 (5)
149 (54)
105 (38)
131 (47)
28 (10)
122 (44)
143 (52)
11 (4)
28 [21e35]
1 [0e5]
19 (7)
171 (60)
152 (53)
152 (53)
83 (29)
109 (45)
111 (45)
24 (10)
35 [25e44]
0 [0e3]
15 (6)
117 (46)
86 (34)
96 (38)
61 (24)
0 [0e2]
13 [10e18]
490 (42)
572 (58)
383 (33)
117 (9)
83 (7)
101 (9)
86 (7)
80 (7)
46 (4)
34 (3)
0 [0e2]
14 [11e16]
13 (54)
11 (46)
9 (38)
4 (16)
1 (4)
4 (17)
1 (4)
0 (0)
2 (8)
2 (8)
0 [0e0]
13 [12e20]
40 (33)
80 (67)
27 (22)
13 (10)
0 (0)
12 (10)
14 (12)
10 (8)
8 (7)
5 (4)
0 [0e4]
15 [13e22]
96 (47)
107 (53)
64 (32)
32 (15)
19 (9)
29 (14)
21 (10)
20 (10)
20 (10)
16 (8)
0 [0e0]
14 [12e19]
133 (48)
143 (52)
107 (39)
26 (9)
36 (13)
32 (12)
31 (11)
16 (6)
8 (3)
5 (2)
0 [0e2]
13 [10e18]
119 (41)
168 (59)
96 (33)
23 (7)
16 (6)
14 (5)
8 (3)
22 (8)
6 (2)
4 (1)
0 [0e2]
8 [7e12]
89 (35)
163 (65)
80 (32)
9 (4)
11 (4)
10 (4)
11 (4)
12 (5)
2 (1)
2 (1)
P value
<.001
<.001
<.001
(4)
(13)
(4)
(17)
(17)
(25)
(4)
(17)
(8)
(20)
(13)
(16)
(14)
(13)
(10)
(7)
.029
<.001
<.001
.002
.009
<.001
<.001
<.001
<.001
<.001
.006
<.001
<.001
<.001
<.001
.185
<.001
<.001
IQR, interquartile range; LN, lymph node.
30-day mortality from 8% to 1% between the first and last cohorts
(P < .001), respectively.
Notable interventions
A number of notable interventions occurred during the time
frame of this study. These are highlighted in Fig 3, which demonstrates the trend in number of cases performed and also demonstrates the relative impact on 5-year survival, duration of stay, and
the proportion of patients with more advanced disease.
Discussion
This study gives a unique insight into the changes in gastric
cancer presentation, management, and outcomes during a 30-year
period. Furthermore, it provides 10 years of follow-up, which has
not previously been reported in the field of gastric cancer in a
Western population.
The results presented demonstrate a significant increase in 5year survival during the time period. Overall, the median survival
was 32 months; however, well over 50% of patients were alive at 5years in the latest cohort, compared with under 25% in the first 2
cohorts. In addition, there has been an improvement in short-term
outcomes, with a large drop in the duration of stay of patients such
that the median duration of stay in the final cohort was 8 days,
which corresponded to the institution of an enhanced recovery
pathway, and a fall in inpatient mortality from 4% to 1% in the latest
time frame.
Furthermore, there was a fall in complication rate which may
have contributed toward the duration of stay. Overall complications
fell from 42% to 35%, but more importantly the rate of “significant”
complications (Clavien-Dindo grades 3 and above) has dropped
from 16% to 4% in the latest cohort, which compares favorably with
a recent large national study from the Netherlands.20,21 These more
severe complications are more likely to impact on patient stay and
potentially affect postoperative quality of life.
There are several factors that may have contributed toward
improved outcomes, although it is impossible to establish a direct
cause and effect relationship. The integration of a standardized
enhanced recovery pathway, may have served to ensure uniform
care for patients, with a standardized analgesic regime (which has
dispensed with epidurals and now favors rectus sheath catheters,
and patient controlled analgesia as well as intrathecal diamorphine
at induction),22,23 early mobilization and a uniform approach to
nutrition. This multimodal analgesic regime, without epidural, reduces the incidence hypotension, which can limit a patients’ ability
to mobilize, and may have contributed toward the reduction in
pulmonary complications.
Despite the fall in complications there has been an increase in
treating patients with poorer initial fitness as indicated by American Society of Anesthesiologists (ASA), which was used as a surrogate for this measure. Other patient parameters which may have
S.M. Griffin et al. / Surgery xxx (2021) 1e9
5
Changes to Survival
A
1989-1993
1994-1998
1995-2003
n
24
120
203
Median Survival, months
28.3 (17.5-49.1)
22.5 (19.3-35.1)
28.4 (21.7-41.1)
2004-2008
2009-2013
276 81.4 (53.3-105.7)
287 53.0 (35.5-65.2)
2014-2018
252 NR
64.9
NR
Fig 1. Overall survival in time cohorts and by stage.
contributed toward short-term outcomes include BMI, smoking
status, and alcohol intake. With regards to BMI, there has been a
minimal increase in the median BMI of patients during the study
period from 25 to 26. Perhaps more noticeable was the proportion
of current smokers (defined as smoking within 6 weeks of their
surgery). This has dropped dramatically from 38% to 20%, and
indeed the proportion that have never smoked has risen similarly.
This may have a major contribution toward patients’ improved
postoperative recovery.
The improved survival is perhaps not unexpected given that
perioperative chemotherapy has become the standard of care for
patients with locally advanced disease since the MAGIC study was
published.10 Although the MAGIC study demonstrated a 13%
improvement in 5-year survival associated with the use of perioperative chemotherapy, the results in this study show an almost
doubling of survival in the era of perioperative treatment. However,
perioperative chemotherapy is likely to only account for a small
proportion of the improved outcomes seen, with lower mortality
(down from 8% to 1% in the latest cohorts), and lower morbidity,
which has been shown to lead to poorer long-term outcomes.24,25
In addition, improved patient staging, with better cross-sectional
imaging and laparoscopy to diagnose occult metastatic disease
may have helped contribute improve patient selection and the
optimization of treatment. It is not possible to identify the impact of
6
S.M. Griffin et al. / Surgery xxx (2021) 1e9
B
1989-1993
1994-1998
1995-2003
2004-2008
2009-2013
2014-2018
n
24
120
203
276
287
252
Median Survival, months
28.3 (17.5-49.1)
22.5 (19.3-35.1)
28.4 (21.7-41.1)
81.4 (53.3-105.7)
53.0 (35.5-65.2)
NR 64.9
NR
Fig 1. (continued).
individual changes in improving these outcomes, but it is likely to
be multifactorial, with a standardized surgical technique used by all
the surgeons,11 an experienced team involved in staging and
managing patients post-surgery, and most latterly a multifaceted
enhanced recovery pathway, which takes a holistic approach to
patient care.
This study also demonstrated a change in presenting symptoms
over 30 years. There was a steady trend toward fewer patients
presenting with weight loss and anorexia and more presenting
with abdominal discomfort and pain. These changes may correspond with increasing access to endoscopy allowing symptoms that
may have previously been ignored to be investigated.26 Indeed,
there were more patients with stage 0 and I disease in the latter
cohorts, although part of this may be owing to the impact of
downstaging by neoadjuvant treatment on patients some of this
might be owing to referrals from primary care based on symptoms
that may have previously been ignored.
It was also noticeable that there was a significant change in
operation performed with approximately 70% of early operations
being a total gastrectomy, which fell to around 40% in the latter
cohorts. This is in contrast to what has been previously documented with a trend toward more proximal and junctional cancers.27 Although proximal tumors are associated with obesity,
which did not change greatly over the time period, and greater
sociodemographic index, it is perhaps more likely that this trend is
owing to an inherent ethos amongst the department to treat
S.M. Griffin et al. / Surgery xxx (2021) 1e9
A
7
B
C
Fig 2. Five-year survival for (A) stage I, (B) stage II, and (C) stage III disease during each of the time periods.
junctional tumors by esophagectomy, which were not included in
this study.
The major shortcoming of this study is that the data are derived
from a single center, so the question remains are these findings
translatable to wider populations? The surgical procedures were
carried out by a small cohort of 12 surgeons with a standardized
approach during the 30 years of this study. To add to this, patients
were looked after on a specialist esophagogastric ward. These all
help demonstrate the excellent outcomes that can be achieved.
Moreover, surgical technique has not changed over the time period,
which helps demonstrate the impact of the other interventions that
have occurred over the time and the need for constantly reflecting
on how patient management can be improved. The most recent
intervention has been the implementation of a prehabilitation
program for all patients undergoing esophagogastric surgery
enabling them to maintain fitness while receiving neoadjuvant
chemotherapy.28 Prehabilitation has been shown to aid patients in
maintaining fitnesss,29 and a pragmatic approach that is accessible
to all patients has been instituted.
Additional upcoming research involves studies evaluating
pathways to help patient rehabilitation with some evidence already
that a multidisciplinary program can improve cardiopulmonary
fitness post-surgery.30 In addition, this study does not include data
about patient comorbidities which may have changed over time.
ASA was used as a surrogate marker of fitness and the results
indicated a greater proportion with a higher ASA grade in the latter
years. This might suggest poorer overall fitness in these patients;
however, other factors, such as being a current smoker at the time
8
S.M. Griffin et al. / Surgery xxx (2021) 1e9
Fig 3. Evolution in number of cases, survival, and duration of stay correlated with major interventions. Bars demonstrate the number of cases each year. CPEX, cardiopulmonary
exercise testing; ERAS, enhanced recovery after surgery; MDT, multidisciplinary team.
of surgery, have fallen significantly and may contribute toward the
fall in pulmonary complications. Furthermore, there is no information on the quality of life of patients after surgery. This is an
important factor given the improved survivorship and will need to
be the focus of future research.
Additional work to aid prognostication for patients to aid
management is an important consideration. The TNM may potentially include histopathological markers, such as perineural and
lymphovascular invasion, which may provide increased accuracy at
prognosis and guide physicians in how patients are followed
up.31e33 The ability to identify biomarkers, which aid with prognostication and help guide decisions regarding the use of neoadjuvant treatment, need further investigation, given the known
deleterious effect of neoadjuvant treatment on fitness,34 and the
routine use of biomarkers such as the presence of microsatellite
instability may influence the patient pathway particularly the use
of perioperative chemotherapy.35
More investigations into the nutritional support of patients
undergoing gastrectomy needs to be evaluated. Although a previous randomized controlled trial from this center did not show any
benefit from omega-3 fatty acid supplementation on clinical outcomes,36 a more recent meta-analysis has shown preoperative
immune modulating nutrition may shorten stay and reduce complications.37 Careful consideration of nutrition in these patients
may also contribute toward improved long-term outcomes particularly with the associated risk of pancreatic insufficiency and
longer term malnutrition.38,39
In conclusion, there has been considerable progress for the past
30 years with regards to both perioperative outcomes and longterm survival in patients with gastric cancer. This study does not
examine patient quality of life which needs to be addressed. All the
patients had open surgery, and it may be that a move toward
laparoscopic surgery could improve these outcomes with several
recent studies suggesting comparable long term outcomes40e42
and the potential for robotic surgery to have an equally effective
oncological profile.43 Although laparoscopic surgery has not been
adopted at this center, there has been recent commencement of a
robotic program. It has been felt by the surgeons involved that this
may confer advantages with excellent visualization and improved
surgical dexterity. Potentially this may provide long-term quality of
life improvements and even add to surgeon longevity. However,
care must be taken not to compromise oncological outcomes in a
drive to perform minimally invasive procedures. Changes in the
management of early gastric cancers toward organ preserving
endoscopic therapy may also need to be considered with further
research required to establish whether endoscopic submucosal
dissection carried any advantage over endoscopic mucosal resection and to determine if organ preserving treatment is achievable in
more advanced cancers.44
This study highlights that continual improvement in outcomes
can be achieved by making changes to the patient pathway. There
are a number of areas for further research, identification of those
who will most benefit from neoadjuvant treatment, the impact of
prehabilitation, and a rehabilitation pathway for patients after
enhanced recovery which may all go to improve outcomes further.
Funding/Support
No direct or indirect funding was received for this work.
Conflict of interest/Disclosure
The authors declare no related conflicts of interest.
Acknowledgment
The authors would like to thank Helen Jaretkze, NOGU datamanager for help with preparation of this manuscript.
S.M. Griffin et al. / Surgery xxx (2021) 1e9
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