ARTICLE IN PRESS

Surgical Oncology (2007) 16, 267275

Available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/suronc

REVIEW

Palliative management of gastric cancer

Steven C. Cunninghama,b, Richard D. Schulickc,
a

Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
Department of Surgery, University of Maryland Medical Center, Baltimore, MD 21201, USA
c
Department of Surgery, The Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Rm.
442, Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231-1000, USA
b

KEYWORDS
Gastric cancer;
Palliation

Summary
Advanced gastric cancer and its palliative treatment have a long and interesting history.
Today, gastric adenocarcinoma is the second leading cause of cancer death worldwide.
Unfortunately, many cases are not diagnosed until late stages of disease, which
underscores the importance of the palliative treatment of gastric cancer. Palliative care
is best defined as the active total care of patients whose disease is not responsive to
curative treatment. Although endoscopy is the most useful method for securing the
diagnosis of gastric adenocarcinoma, computed tomography may be useful to assess local
and distant disease. The main indication for the institution of palliative care is the
presence of advanced gastric cancer for which curative treatment is deemed inappropriate. The primary goal of palliative therapy of gastric cancer patients is to improve quality,
not necessarily length, of life. Four main modalities of palliative therapy for advanced
gastric cancer are discussed: resection, bypass, stenting, and chemotherapy. The choice of
modality depends on a variety of factors, including individual patient prognosis and goals,
and should be made on case-by-case basis. Future directions include the discovery and
development of serum or stool tumor markers aimed at prevention, improving
prognostication and stratification, and increasing awareness and education.
& 2007 Elsevier Ltd. All rights reserved.

Contents
History, epidemiology, and definitions.
Clinical presentation . . . . . . . . . . .
Classification and staging. . . . . . . . .
Diagnosis . . . . . . . . . . . . . . . . . . .
Indications for palliative management
Aims of palliative management . . . . .
Modalities for palliative management .

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Corresponding author. Tel.: +1 410 614 9879; fax: +1 410 614 9882.

E-mail address: rschulick@jhmi.edu (R.D. Schulick).

0960-7404/$ - see front matter & 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.suronc.2007.08.004

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268
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268
269
269
269
270

ARTICLE IN PRESS
268

S.C. Cunningham, R.D. Schulick

Resection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Bypass. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Stenting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Gastrectomy, peritonectomy, and perioperative intraperitoneal chemotherapy. . . . . . . . . . . . . . . . . . .
Future directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Prognostication and stratification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Increasing education and awareness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Key points . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

History, epidemiology, and definitions

Advanced cancer has been a problem at least since the
Jurassic Period, as evidenced in the metastatic cancer
recently described in a dinosaur fossil [1,2]. The earliest
documentation of advanced human cancer is found in the
Ebers and Smith papyri, which date from ca. 1600 BC and
contain what may be the first reports of gastric cancer [3].
A case of an advanced tumor, with its surrounding swollen
veins resembling a crab and its limbs, suggested to the
ancient Greeks to coin the term cancer (carcinoma,
from karkinoma, from karknoma), a word that derives from
the word for crab [4,5]. In 1881, the first successful
resection of an advanced gastric cancer was performed in
Vienna by Theodor Billroth [6].
Today, gastric cancer is the second leading cause of
cancer death worldwide [7] and there are 22,280 new
patients with gastric cancer annually in the United States,
11,430 of whom will die of their disease [8]. The
epidemiology of gastric cancer was recently reviewed [9].
While the incidence of distal gastric cancers is decreasing,
gastric cardia tumors, paralleling adenocarcinoma of the
distal esophagus, are increasing in incidence, accounting for
nearly half of all stomach cancers among men in the United
States and the United Kingdom. Incidence peaks in the fifth,
sixth, and seventh decades of life and men bear a two-fold
and five-fold greater risk than women for developing
noncardia and cardia cancers, respectively. In addition,
incidence rates are higher among lower socioeconomic
classes.
In a recent review of the gastric cancer literature, the
5-year survival rates following resection of gastric adenocarcinoma in North America and Europe, with and without
negative margins, was 4050% and 2040%, respectively
[10]. Unfortunately, many cases are so advanced at diagnosis
as to preclude curative resection [1114], a fact that
underscores the importance of palliative treatment of
advanced gastric cancer.
Review of the literature on palliative treatment of
advanced cancer reveals that the term palliation is
employed in an unhelpfully wide variety of ways [1517].
According to the Oxford English Dictionary, to palliate, from
the Latin, palliare (to cloak or cover), means to alleviate
without effecting a cure [5]. In agreement with the World
Health Organizations definition, palliative care has been
defined in an American College of Surgeons Palliative Care
Symposium as the active total care of patients whose
disease is not responsive to curative treatment [18,19].

270
271
271
271
272
272
272
272
272
273
273

Regarding gastric cancer in particular, surgical palliation has

been defined as a procedure employed with the primary
intention of improving quality of life or relieving symptoms
caused by an advanced gastric malignancy [16,17].

Clinical presentation
Patients with gastric cancer most commonly present with
pain and weight loss, but may be asymptomatic. Dysphagia
may also be present if tumors are proximal, but when they
are distal, nausea and vomiting may predominate from
gastric outlet obstruction. Early satiety may be more
common in cases of diffuse infiltrative gastric adenocarcinoma, also known as linitis plastica, whose characteristic
appearance earned it the common name leather-bottle
stomach. Advanced gastric cancer, unlike early cancer, may
present characteristic findings on physical examination,
such as palpable disease felt in the left supraclavicular
fossa (Virchows node), in or around the umbilicus (Sister
Mary Joseph node), in the pelvic cul-de-sac (Blumers shelf,
via rectal exam), on the ovaries (Kruckenbergs tumor, via
pelvic exam), and, uncommonly, in the left axillary fossa
(Irishs node). Advanced lesions can cause bleeding, perforation, and obstruction and the severity of these presentations
ranges from mild and elective to severe and emergent.

Classification and staging

Gastric tumors are classified predominantly depending on
the location of origin. In one of the largest and most recent
series of gastric adenocarcinoma in North America, tumors
most commonly originated in the cardia in 37% patients,
followed by the antrum in 20%, the body in 5%, the fundus in
4%, the pylorus in 3%, and multiple or overlapping locations
in 31% [10]. This distribution may, however, represent a
skewed population that presents to a high-volume academic
center, as opposed to the community setting, where most
surgeons operate.
Gastric cancers are staged using the American Joint
Committee on Cancer Tumor-Nodes-Metastasis (TNM) system
[20] (Table 1). This sixth edition of the AJCC staging system
differs from the previous edition only in the division of stage
T2 lesions (those invading the muscularis propria or the
subserosa) into T2a lesions (invading the muscularis propria)
and T2b lesions (invading the subserosa) [20,21]. TNM stage
correlates significantly with survival following resection of
gastric adenocarcinoma (reviewed in reference [10]).

ARTICLE IN PRESS
Palliative management of gastric cancer

Table 1

269

Staging of gastric adenocarcinoma.

Stage

Tumor

Node

Metastasis

0
IA

Tis
T1

N0
N0

M0
M0

IB

T1
T2a/b

N1
N0

M0
M0

II

T1
T2a/b
T3

N2
N1
N0

M0
M0
M0

IIIA

T2a/b
T3
T4

N2
N1
N0

M0
M0
M0

IIIB

T3

N2

M0

IV

T4
T1-3
Any T

N1-3
N3
Any N

M0
M0
M1

Tis, carcinoma in situ; T1, tumor invades lamina propria or

submucosa; T2, tumor invades muscularis propria (a) or
subserosa (b); T3, tumor penetrates serosa without invasion
of adjacent structures; T4, tumor invades adjacent structures; N0, no regional nodal metastasis; N1, metastasis in 16
regional nodes; N2, metastasis in 715 regional nodes; N3,
metastasis in 415 regional nodes; M0, no distanta metastasis; M1, distant metastasis.
Modified from AJCC staging, 6th ed. Abbreviations: HA,
hepatic artery; PV, portal vein; LN, lymph node; AJCC,
American Joint Committee on Cancer [permission not
requested by authors].

Diagnosis
Endoscopy is the most useful method for securing the
diagnosis of gastric adenocarcinoma. While early disease
may occur as flat plaques, subtle polypoid lesions, or shallow
ulcers, advanced cancers are typically ulcerated with raised
or irregular borders and a necrotic base. Differentiation of
malignant from benign lesions is possible by endoscopic
biopsy, with an accuracy of 495% if multiple biopsy
specimens are obtained [9599]. Brush cytology may further
increase diagnostic accuracy [22]. Other endoscopic techniques are currently under investigation, such as fluorescence
endoscopy [23], narrow-band imaging [24], and optical
coherence tomography [25], but will be more relevant for
early than for advanced cancers.
The role of endoscopic ultrasound (EUS) in the staging of
gastric cancer has been studied. Although initial studies
were optimistic, reporting an accuracy of 88% for T stage
and nearly 80% for N stage [26], subsequent studies found Tand N-stage accuracies to be only 68% and 5766%,
respectively [27,28], suggesting that this modality may have
limited usefulness in the staging of gastric cancer patients.
Although now largely supplanted by endoscopy, barium
contrast radiography has played an important role in the
diagnosis of gastric neoplasms. When double-contrast (air
and barium) methods are used, diagnostic accuracy may
approach 90%. Findings typical of a malignant gastric
neoplasm such as gastric adenocarcinoma include the

presence of a gastric wall mass, mucosal ulceration, or

other loss of mucosal detail, and distortion of the gastric
contour. Despite such a respectable diagnostic accuracy,
barium contrast radiography, unlike gastrointestinal endoscopy, suffers from the inability to perform biopsy and
therapeutic maneuvers during the same intervention.
Computed tomography (CT) and magnetic resonance
imaging (MRI) are both useful not only for primary diagnosis
of gastric adenocarcinoma, but also for secondary diagnosis
of metastatic disease. CT has the advantage of being faster,
less expensive, and more widely available. When oral and
intravenous contrast is used, CT can provide useful detail of
tumor infiltration, ulceration and visceral metastasis. While
the ability of CT to detect lymphatic metastasis has been
poor in the past [29] more recent studies have concluded
that helical CT is effective for detection of metastatic
lymphadenopathy from gastric cancer [30].
However, even state-of-the-art abdominopelvic CT scanning
techniques cannot reliably detect cancerous involvement of
normal-sized lymph nodes, or enlargement of lymph nodes
outside of the abdomen and pelvis, and have limited ability to
detect peritoneal metastasis. Imaging of peritoneal metastasis
was recently reviewed by Lim et al. and may be achieved by a
combination of CT and positron emission tomography (PET)
scanning: CT evidence of peritoneal metastasis includes nodular,
plaque-like or infiltrative lesions in the peritoneal fat or on the
peritoneal surface; parietal peritoneal thickening or enhancement; small bowel wall thickening or distortion, and, most
commonly, ascites [31]. Evidence of peritoneal metastasis on
PET scanning with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)
includes two main patterns: (1) a diffuse FDG uptake throughout
the entire abdomen and pelvis, obscuring normally discrete
visceral outlines, and (2) discrete foci of FDG uptake in locations
that do not correspond to known visceral or nodal locations
[31]. It should be noted, however, that while PET is an area of
active experimentation, it is still considered an investigational
modality and is not currently universally reimbursed.

Indications for palliative management

Palliation should be regarded not as the opposite of cure,
but rather as having its own distinct indications, goals and
challenges, with consideration for each patient on a caseby-case basis [32,33]. In general, the primary indications for
the institution of a palliative course of therapies include the
presence of an illness for which curative treatment is
deemed inappropriate, as determined by the patient or the
disease, usually by both. Unfortunately, few data exist that
define the specific indications for a palliative course in the
management of gastric cancer, and this decision is often
made based on the combined experiences and impressions
of the patient and surgeon.

Aims of palliative management

The goals of palliative treatment are most simply stated as
improving quality, not necessarily length, of life. The unique
challenges of palliative therapy are manifold but the most
fundamental challenge may be to find a balance between
being honest and forthright with patients regarding prognosis and still supporting in them a sense of hope regarding

ARTICLE IN PRESS
270

S.C. Cunningham, R.D. Schulick

quality of life [15]. This often involves a redirection of

expectations (from quantity to quality of life) that challenges patients and providers alike. According to a Society
of Surgical Oncology survey [34], surgeons, when asked what
they considered the important goals of palliative procedures, reported that symptom relief, pain relief, and
maintaining patient independence and function were most
important, followed by symptom avoidance, decreased
hospitalization, improved body image, and minimizing
burden of care. The goal of increasing patient survival
received the lowest priority scores, and had the broadest
range of responses. Nevertheless, as discussed below, some
have argued that so-called palliative gastrectomy is a
worthwhile procedure, in part for its possible ability to
extend survival in patients with advanced gastric cancer
[3538]. In any case, any intervention with palliative intent
should be undertaken with due attention paid to the
meaning that the patient ascribes to the intervention, since
the meaning perceived by the patient impacts the patients
response to the intervention [39]. The need for paying such
attention becomes clear when one considers that any
palliative intervention is an intervention that may well be
one of the last major events in the patients life.

Modalities for palliative management

Resection
Table 2 shows the results of select studies evaluating the
role of resection in cases of advanced gastric cancer. One of

Table 2

the first studies to evaluate the role resection as a palliative

treatment for advanced gastric cancer was published in 1958
by Lawrence and McNeer in New York [40]. They evaluated
1623 cases of gastric cancer from 1931 to 1955 and found
that while 34% had a curative resection, nearly half
underwent a noncurative operation, half of whom (23% of
the total) underwent a palliative operation. The vast
majority (98%) of these palliative operations were bypasses
in the 1930s, whereas by the 1950s the majority (74%) were
resections. Of those resections, subtotal, but not total
gastrectomy was found to be effective palliation: more than
half of the subtotal resections had relief of symptoms that
were graded good or fair. Subsequent work done by
ReMine and published in 1979, and by Meijer et al. in 1983,
was consistent with the conclusions of the earlier study, viz.,
total gastrectomy was found not to be a satisfactory
palliative procedure compared to partial gastrectomy
[41,42]. Despite these studies, and perhaps facilitated by
the same advances in surgical technique that may have been
responsible for the aforementioned trend in the 1950s
toward more resection as the palliative operation of choice,
total gastrectomy was suggested in 1991 by Monson et al. to
be a worthwhile palliative procedure, providing prolongation of good quality of life [86]. However, because only
tumor location, and not tumor extent per se was the
indication for total gastrectomy in 70% of the 53 patients in
Monsons study, comparison of this study with previous and
subsequent studies of advanced-stage gastric cancer may
not be possible. Since the late 1990s, there have been
several more series published (Table 2). Most of these
studies qualified the extent of the advanced gastric cancer,

Selected series of palliative gastric resection.

Author [reference]

N resected

Morbidity/
mortality (%)a

Median survival
(mo)

Increased
quantity of life
claimed

Increased quality
of life claimed

Lawrence and McNeer [40]

ReMine [41]
Meijer et al. [42]
Monson et al. [86]
Ouchi et al. [45]
Hartgrink et al. [46]
Medina-Franco et al. [43]
Kahlke et al. [47]
Samarasam et al. [44]
Saidi et al. [38]

108
52
26
53c
64
156
40
123
107
24

NR/1128
NR/6.5
NR/7.7
NR/8
NR/1.6
50/20
26/2.6
4049/815
NR/NR
33/8.7

9
NR
9.5
19
NR
8.1
13
46
24
13i

Yes
Yes/Nob
Yes/Nob
Yes
Yes/Nod
Yes/Nof
Yes
No
Yes/Noh
Yes

Yes/Nob
NR
Yes
Yes
Noe
NR
Yes
Yes/Nog
Yes
NR

Abbreviations: N, number; M&M, morbidity and mortality.

a
For all patients.
b
Yes, if no partial gastrectomy; No, if total.
c
All operations were total gastrectomies for advanced cancer, but indications were tumor location (proximal) in 70% of cases and
tumor extent in 30%.
d
Yes, if no peritoneal metastases do not spread beyond adjacent peritoneum.
e
Hospital-free survival taken as surrogate for QOL.
f
Yes, if one or no sites of tumor spread; No, if more.
g
Yes, if major symptoms (gastrointestinal bleeding from the tumor, perforation, ileus, or gastric obstruction); No, if minor symptoms
(all other patients).
h
Yes, if two or fewer sites of tumor spread; No, if more.
i
Mean, not median.

ARTICLE IN PRESS
Palliative management of gastric cancer

271

and found a survival benefit after resection if the number of

distant sites of spread was limited to one or two [38,4346].
Regarding increased quality of life, i.e., the equally if not
more important consideration in judging the benefit of a
palliative operation, the last six studies in Table 2 are
divided on this issue: three claim an increased quality of life
after resection [43,44,47], and three either claim that there
is not an increase, or do not report on quality of life
[38,45,46].

Bypass
With some consistency, studies evaluating palliative operations using operative bypass alone in the treatment of
advanced gastric cancer have shown no or little benefit
[40,41,43,45]. Although resection has been found to be
superior palliation compared to bypass in most patients,
there is some evidence that in those patients whose primary
symptoms are due to gastric outlet obstruction, bypass
operations may provide symptomatic relief, which occurred
in 60% of patients according to one study [43]. When
laparoscopic bypass was compared to open bypass in a series
of 68 patients with advanced gastric cancer undergoing
gastrojejunostomy (GJ) in Korea, laparoscopic bypass was
found to be superior to open GJ [48]. Compared to open
bypass, laparoscopically operated patients had less suppression of immune function, less pain, earlier recovery of bowel
movements, and shorter hospital stay. However, quality of
life was not analyzed in detail and therefore little
conclusion can be made from this study regarding the
effectiveness of bypass, per se, as a palliative procedure.
Furthermore, for the group of patients who have gastric
outlet obstruction as the primary source of their symptoms,
gastroenterostomy has been found by at least one prospective randomized study to be less effective than endoscopic
stenting [49]. The decision of operative bypass versus
endoscopic stenting should be made on a case-by-case basis
taking into account each the patients life expectancy.

Stenting
The palliative treatment of malignant gastric outlet
obstruction by stenting was first reported in 1992 by Truong
et al. in Germany [50]. Since then there have been several
Table 3

hundred cases reported in the literature, including single

case reports, case series, and randomized prospective trials
(Table 3). The vast majority are case reports and series,
which are recently summarized in a metaanalysis of 606
cases [51]. In approximately one-third of cases, obstruction
was caused by gastric cancer, one-third by pancreatic
cancer, and one-third by other cancers. Initial stent
deployment was successful in 97% of cases, and clinical
success claimed in nearly 90% of cases. Severe complications
occurred in only 1% of cases, but the overall complication
rate was 28% and late failure by obstruction of the stent
occurred in 17% of patients, typically due to progressive
tumor growth. The most commonly employed device was
the WallstentTM (Boston Scientific, Natwick, MA, USA) (in
74% of patients), which has the advantage over other stents
that it can be recaptured for repositioning and redeployment.

Chemotherapy
The available literature on chemotherapy for advanced
gastric cancer suggests that there may be a small benefit.
However, trials are generally based on the premise that the
gold-standard primary endpoint is patient survival, i.e.,
quantity, not necessarily quality, of life afforded the
patient. Chemotherapy for advanced gastric cancer was
recently reviewed [5254], and need not be rereviewed
here. In brief, a number of trials have indeed produced
evidence that chemotherapy improves survival compared to
best supportive care [5557]. Select recent phase II
randomized controlled trials are summarized in Table 4.
Although there is a wide range of combinations of
chemotherapeutic agents tested in clinical trials, most
regimens are 5-fluorouracil (5-FU)-based. In Britain and
Australia, the combination of epirubicin, cisplatin, and 5-FU
(ECF) is widely used, but has not received wide acceptance
in the United States, likely because of concerns for systemic
toxicity [58]. In the recently reported randomized controlled trial of perioperative ECF versus resection alone,
which claimed a significant survival benefit for gastric
cancer patients in the ECF arm, 490% of those patients
suffered nausea, vomiting, diarrhea, neurological effects,
skin effects, stomatitis, hemoglobinopathy, thrombocytopenia, and other hematologic abnormalities [59].

Selected studies of stenting of malignant obstruction in advanced gastric cancer.

Author [reference]

Stent type

N patients
stented

Initial success
rate

Complications
(%)

Recurrence
(late
obstructive
symptoms)

Mean
survival
(mo)

Increased
quality of life
claimed

Kim et al. [87]

Adler and Baron [88]
Mittal et al. [89]
Dormann et al. [51]
Jeong et al. [90]
Fiori et al. [49]
Mosler et al. [91]

SECS
SEMS
NR
Meta-analysis
SEMS
SEMS
SEMS

26
36
16
606
24
9
36

90
100
100
97
96
100
92

0
6
0
28
20
11
8

15
22
0
17
20
0
36

4
3
2
3
4
NR
4

Yes
Yes
Yes
Yes
Yes
Yes
Yes

Abbreviations: SECS, self-expanding coil stents; SEMS, self-expanding metal stents; NR, not reported.

ARTICLE IN PRESS
272

Table 4

S.C. Cunningham, R.D. Schulick

Selected recent phase-II chemotherapy trials for advanced gastric cancer.

Author [reference]

Arms

Conclusions

Response rate (%)

Improved QOLa

Thuss-Patience [92]

DF versus ECF

38

NR

Moehler [93]

ILF versus ELF

43

NR

Park [94]

PF versus DF

DF provided similar survival

and progression times, but
less toxic
ILF provided better response
rate
Similar response rates

42

Improved functional but

worse symptoms scores in
both arms

Abbreviations: DF, docetaxel and 5-FU; ECF, epirubicin, cisplatin, and 5-FU; ILF, irinotecan, 5-FU, and leucovorin; ELF, 5-FU, leucovorin,
and etoposide; PF, paclitaxel and 5-FU.
a
Quality of Life (as measured with a validated version of the European Organization for Research and Treatment of Cancer [EORTC]
QLQ-C30 Questionaire).

Gastrectomy, peritonectomy, and perioperative

intraperitoneal chemotherapy
The treatment of advanced gastric cancer with the
combination of gastrectomy, peritonectomy, and intraperitoneal chemotherapy has been evaluated for patients with
tumors that are locally metastatic (to peritoneum). Several
studies have recently been published showing some promise
for highly selected patients [6066]. However, despite the
advanced stage of the patients gastric cancers, these
studies are generally performed with curative, not palliative, intent, placing them more or less outside the scope of
the current review. Recent work on this modality has been
reviewed elsewhere [37,67,68].

Future directions
Prevention
Clearly the best way to improve the treatment of advanced
gastric cancer is to prevent it. To this end, population-wide
screening programs are in place in high-incidence regions of
the world, such as Japan [9]. However, in North America and
Europe, where the incidence of this devastating disease is
lower, the ability to effectively screen is prohibitively low,
resulting in the irony that cases present at more advanced
stages in low-incidence regions. Nevertheless, other novel
screening interventions await development, such as immunohistochemical or endoscopic detection of early occurrence or recurrence in selected high-risk populations. For
example proteins such as glycoprotein-87, claudin-4, stratifin, MKK4, Das-1, and liverintestinal cadherin have
recently been identified immunohistochemical markers of
gastric cancer precursor lesions [6972]. If antibodies to
these proteins could be linked to endoscopically visible tags,
then early occurrence or recurrence could theoretically be
detected endoscopically without biopsy in high-risk populations. Other, still less-invasive techniques for cancer screening are currently under evaluation. The most promising,
given its noninvasive nature, is screening of fecal samples
for evidence of undiagnosed cancer. Following in the steps
of the fecal occult blood test and genetic screening of fecal
samples for colon cancer, preliminary studies have begun to

evaluate the role of gastric cancer markers, including

pyruvate kinase and carcinoembryonic antigen, in stool
samples [73,74].

Prognostication and stratification

Given that improved prevention of advanced gastric cancer
will not be absolutely successful, another important aim for
future work is to improve the ability of practitioners to more
accurately prognosticate the course of disease and to better
stratify patients. Many papers report the ability of novel
markers to prognosticate disease course. Unfortunately,
many of these suffer from a number of problems: some are
never validated in independent data sets, others are
immunohistochemical markers whose optimal labeling intensity cannot be calibrated due to a paucity of knowledge
of the markers biology, and others have not included
sufficient numbers of samples. In our institution, we have
recently sought to overcome all three problems by taking
advantage of a large gastric cancer database [10], using a
genetically calibrated immunohistochemical assay [75] to
test tissue microarrays from database patients, and confirming the findings of a previous study using an independent
dataset [76]. The marker in these studies was the tumorsuppressor protein MKK4. The MKK4 gene is lost in about
510% of nearly every cancer type evaluated [7779].
Because loss of MKK4 protein immunolabeling in gastric
cancer sample was found to be highly significantly associated with poor survival after resection of advanced gastric
cancer [76], it may prove useful for stratification. For
example, the identification of a tumors MKK4 status as
detected on a preoperative needle biopsy could plausibly
identify more aggressive disease in patients who might
benefit from neoadjuvant therapy or from an extended
resection. For a given population, MKK4 immunolabeling of
advanced gastric cancer samples may be used to increase
the power of clinical trials by increasing the ability to
stratify enrolled patients.

Increasing education and awareness

As discussed above, the term palliation is used in a
wide range of sometimes inconsistent ways [1517]. This

ARTICLE IN PRESS
Palliative management of gastric cancer
observation suggests the need for increasing awareness and
education among practitioners. To this end, the Palliative
Care Taskforce of the American College of Surgeons (ACS)
has recently held several palliative care symposia
[18,8083], including a focus on palliative care in surgical
resident education [80]. Recent initiatives include such as
the National End-of-Life Residency Training Project [84,85],
the addition of palliative care educational material to the
ACS website, and the incorporation of test questions on
palliative care into future editions of the Surgical Education
and Self-Assessment Program.

Key points
1. Palliative care is best defined as the active total care of
patients whose disease is not responsive to curative
treatment.
2. Endoscopy is the most useful method for securing the
diagnosis of gastric adenocarcinoma, and computed
tomography is useful to assess local and distant advanced
disease. PET and EUS are two investigational adjunctive
means of diagnosis and staging.
3. The primary goal of palliative therapy of gastric cancer
patients is to improve quality, not necessarily length, of
life.
4. Resection of advanced gastric cancer may prolong
survival, but the literature is divided regarding the
effect of resection on quality of life.
5. Surgical bypass alone is not supported by the weight of
the literature as a worthwhile palliative intervention for
most patients with advanced gastric cancer. Some
evidence does suggest that in those patients whose
primary symptoms are due to gastric outlet obstruction,
bypass operations may provide symptomatic relief, and
laparoscopic bypass, when possible, provides better
palliation than open bypass.
6. Endoscopic stenting is a well-tolerated intervention
initially effective at relieving symptoms of obstruction
in about 97% of cases, but the number of patients
suffering late recurrent obstructive symptoms approaches 20%.
7. Several recent randomized clinical trials of chemotherapy
for advanced gastric cancer have shown a small survival
benefit, but the impact of quality of life in unclear.
8. Important areas for future work include developing novel
serum or stool tumor markers aimed at prevention,
improving prognostication and stratification, and increasing awareness and education.

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