CARCINOMA STOMACH

GASTRIC CARCINOMA
Chairperson:-Dr NARAYAN HEBSUR
ASSOCIATE PROF AND UNIT CHIEF
DEPT OF GENERAL SURGERY,KIMS
HUBLI
Speaker:-Dr ABHISHEK KUMAR,3rd yr pg

DIVISIONS OF STOMACH –
 Cardia
 Fundus
 Body / Corpus
 Pyloric antrum
 Pyloric canal

GE Junction –
 Z – line /
Squamocolumnar jn.
 Rugal folds
 Fat pad
 Collar of Helvetius /
Loop of Willis

PYLORUS
• Prepyloric vein of
Mayo

VASCULAR SUPPLY
CELIAC TRUNK
• Lt gastric artery
• Rt gastric artery
• Lt gastroepiploic artery
• Rt gastroepiploic artery
• Short gastric arteries
• Inferior phrenic arteries

LYMPHATICS
4 zones
Celiac group
Thoracic
duct
Paracardial
LGE nodes
RGE nodes
Left gastric nodes

LAYERS OF STOMACH
SubserosalCT

INNERVATION
PARASYMPATHETIC
• Vagus -
left/anterior
- hepatic branch
- anterior n. of Latarjet
right/posterior
- criminal n. of Grassi
- celiac branch
SYMPATHETIC
• Greater splanchinic nerve (T5-9)
ENTERIC NERVOUS SYSTEM
• Meissner’s plexus (submucosal)
• Auerbach’s myenteric plexus
Rt. vagus
Celiac
br.

GASTRIC NEOPLASM
Epithelial
Mesenchymal
1.Primary
Adenocarcinoma
Gastrointestinal stromal tumors
‘GIST’
Lymphoma
2. Secondary:
invasion from adjacent tumors.
Benign Malignant

GASTRIC NEOPLASMS BENIGN TUMORS
•Gastric polyps
•They are usually an incidental finding on endoscopy
detected in 2-4% of gastroscopic evaluation.
•Fundic gland polyps constitute 47% of all the gastric
polyps and do not have malignancy potential.
•Typically presents as 2-3mm sessile lesions in body and
fundus
•Gastric polyps can occur in 53% of the patients with
familial adenomatous polyposis or gardners syndrome.
•May be associated with colorectal neoplasms in 60% of
patients.
Cancer: Principles and Practice of Oncology 6th edition (July 2001): by Vincent T. Devita (Editor), Samuel Hellman,
Steven A. Rosenberg (Editor) By Lippincott
Williams & Wilkins Publishers

GASTRIC POLYPS are of two types :
•Hyperplastic
•Adenomatous
Hyperplastic polyps are most frequently observed polyps
and constitute 28-75%(1) of all gastric polyps.
•They usually arise in the setting of chronic atrophic
gastritis 40-75%(2) of the time.
•Frank adenocarcinoma is detected in 2%(3) of
hyperplastic polyps , when detected polypectomy is
indicated.
1,2,3Cancer: Principles and Practice of Oncology 6th edition (July 2001): by Vincent T. Devita (Editor), Samuel
Hellman, Steven A. Rosenberg (Editor) By Lippincott

ADENOMATOUS POLYPS
•Account for 10% of all the gastric polyps
•Most commonly are solitary , sessile ,Antral
Adenomas are of 3 types
-Tubular
-Tubulovillous
-Villous

•Gastric adenocarcinomas may be found in
21% of cases with increased risk in larger size
and villous variety.
•Polyps > 4cms in diameter may harbour
carcinoma in 40% of the time.
•Focal carcinomas were found in 6% of flat
tubular adenomas and 33% of villous and
tubulovillous adenomas.

TREATMENT :
•Endoscopic polypectomy is sufficient treatment if entire
polyp is removed and there is no invasive cancer in the
specimen.
•Operative excision - sessile lesions more than 2 cms.
Polyps found to have areas of invasive tumor or
-polyps symptomatic to pain or bleeding.
•Because of increased risk for coincident gastric
carcinoma these patients are to be followed closely by
serial endoscopies .

Introduction.
•Carcinoma stomach is the major cause of mortality
world wide.
•Its prognosis tends to be poor with cure rates little
better than 10-15%, better results were obtained in
Japan where disease is common.
•It is essentially a curable disease provided it is detected
at an appropriate stage and treated adequately,
•Early diagnosis is the key to success.
•Only treatment modality that is able to cure the
disease is resectional surgery.

Gastric Carcinoma
55 year old Japanese male who is living in Japan
& working in industry.
DEFINITION Malignant lesion of the stomach.Epidemiology & Risk Factors
Can occur at any age
But Peak incidece
Is 50-70 years old.
It is more aggressive
In younger ages.
Japan has the world
highest Rate of
gastric cancer.
Studies have confirmed
that incidence decline in
Japanese immigrant to
America.
dust ingestion
from a variety
of industrial
processes
may be a risk.
Twise more common
In male than in female
Incidence of Gastric Carcinoma:
Japan 70 in100,000/year
Europe 40 in 100,000/year
UK 15 in 100,000/year
USA 10 in 100,000/year
It is decreasing worldwide.

THE MAGNITUDE OF PROBLEM
Male : Lung > Prostate > Colorectal > Stomach
4th most common cancer in men
Female : Breast > Cervix > Colorectal > Lung > Stomach
5th most common cancer in women
• 2nd most commom cause of cancer death
• Poor prognosis
• India : Kashmir - 36/1,00,000
Chennai - 15/1,00,000
Bangalore - 10.6/1,00,000
 Around 45-50% of gastric carcinoma present with an
inoperable disease.

Gastric Carcinoma:
Risk Factors
Predisposing :
1. Pernicious anemia
& atrophic gastritis
(achlorhydra)
2. Previous gastric
resection
3. Chronic peptic ulcer
(give rise to 1%)
4. Smoking.
5. Alcohol.
Environmental:
1.H.pylori infection
Sero(+)patients
have 6-9 folds risk
2.low
socioeconomic
Status
3. Nationality
(JAPAN)
4. Diet (prevention)
Genetic:
1.Blood group A
2.HNPCC:
Heriditory non-
polyposis colon
cancer.

•The etiology of gastric cancer is likely multifactorial.
Factors Associated with Increased Risk of Developing
Stomach Cancer

RISK FACTORS
Nutritional
• Salted/smoked meat or fish (nitrate  N-nitroso compounds)
• Low fresh fruits and vegetable (ascorbic acid)
• High complex carbohydrate consumption
• Low fat or protein consumption

Environmental
• Poor food preparation (smoked, salted)
• Lack of refrigeration
• Poor drinking water (e.g., contaminated well water)
• Smoking
Medical
• Prior gastric surgery (bile gastritis)
• H. pylori infection (not a/w tumors of cardia)
• Gastric atrophy and gastritis

Hereditary
• Hereditary diffuse gastric cancer (E-catherin – CDH1 gene)
80% lifetime incidence
prophylactic total gastrectomy
• Familial Adenomatous polyposis (APCgene, MUTYH gene)
10%-20% risk ∞ size
Pedunculated- Endoscopic removal
Sessile and >2cm- excise
• Duodenal Polyps
• Li – Fraumeni syndrome / SBLA syndrome (p53)
• Lynch syndrome / HNPCC -hereditary nonpolyposis colorectal cancer (MLH1 or
MSH2 mutation)
Others
• Male gender
• Pernicious anaemia (achlorhydria)
• Proto oncogene overexpression – c-met , k-sam , c-erbB2
• Inactivation of tumor suppressor gene – p53 and p16

H.Pylori & Gastric carcinoma
• RESERVOIRS: human, primates, cats,
sheeps.
• Gram-negative spiral bacillus.
• Grows at pH: 4.5-9
• M/C site of colonisation - antrum

Virulence :
cagA gene
Mutation : p53
Over-expression : COX-2, cyclin D2
Decrease expression : p27
Microsatellite instability

PPI and Gastric cancer
Impact of PPI on
incidence of gastric
cancer has not been
elucidated.
....Sabiston
textbook of surgery 19th ed.
• PPI blocks H+-K+ pump
• Hypergastrinemia
• Hyperplasia of G-cells & ECL cells
• Carcinoid tumors in rats
In patients with H.pylori on long term PPI,
the low acid environment allows bacteria
to colonize the gastric body, leading to
corpus gastritis.
1/3rd develop atrophic gastritis.
(a risk factor for carcinoma)

HISTOLOGICAL TYPES OF GASTRIC CANCER
• Adenocarcinoma – 90%
• Lymphoma – 5%
• GIST – Gastrointestinal stromal tumors – 2%
• SCC – Squamous cell carcinoma - <1%
• Carcinoid tumors - <1%
• Adenocanthoma - <1%
• Signet ring cell Carcinoma
• Although no normal lymphoid tissue is found in
the gastric mucosa, the stomach is the most
common site for lymphomas of the gastrointestinal
tract.

Signet ring cell carcinoma (SRCC)
• Rare form of highly malignant adenocarcinoma
• Cells contain abundant mucin in the cytoplasm. So nucleus is shifted to periphery to
produce “signet ring” shape.
• Location – M/c in stomach; and less frequently in breast, gallbladder, urinary bladder,
and pancreas
• Contrary to others gastric cancer, the incidence of SRCC of the stomach is rising.
• SRCC tumors grow in characteristic sheets, which makes diagnosis using standard
imaging techniques, like CT and PET scans, less effective.
• Causes:
- inherited - mutations in CDH1 gene (cell-cell adhesion glycoprotein E-cadherin)
Once these cells lose E-cadherin, their motility increases
- APC gene mutation
• Prognosis
Early SRCC – better or atleast similar to than of non-SRCC
Advanced SRCC – poor than non-SRCC and lower chemosensitivity and peritoneal
carcinomatosis is the most frequent metastatic site.
A ring that kills….

PATHOLOGIC CLASSIFICATION
1) Borrmann classification system
(1926)
2) Lauren Classification System
(1965)
3) WHO System (1990)

• Based on macroscopic apperance
• Useful as endoscopic finding
BORRMANN CLASSIFICATION
Protruded type
Depressed type
Type 1
Type 2
Type 3
Type 4
Type 5
Phymatoid/polypoid
Ulcerative
Infiltrative ulcerative
Diffuse infiltrative
Can’t be classified

INTESTINAL type DIFFUSE type
Environmental Familial
Gastric atrophy, Intestinal metaplasia Blood type A
M > F F > M
Increasing incidence with age Younger age group
Gland formation Poorly differentiated
Hematogenous spread Transmural, lymphatic spread
Microsatellite instability
APC gene mutation
Decreased E-cadherin (CDH1 gene)
Inactivation of tumor suppressor genes p53, p16
Exophytic, bulky lesion Ulcerating lesion
Frequent intraperitoneal metastasis.
LINITIS PLASTICA
LAUREN CLASSIFICATION

WHO Classification of Gastric Cancer
Classification based on morphologic features
 Adenocarcinoma – divided according to the growth
pattern in :
- papillary
- tubular
- mucinous
- signet ring
 Adenosquamous cell carcinoma
 Squamous cell carcinoma
 Undifferentiated
 Unclassified

Spread of Gastric Cancer
Direct Spread
Blood-borne
metastasis
Lymphatic spread
Transperitoneal
spread
Tumor penetrates the
muscularis, serosa &
Adjacent organs
(Pancreas,colon &liver)
What is important here is
Virchow’s node
(Trosier’s sign)
Usually with extensive
Disease where liver 1st
Involved then lung &
Bone
This is common
Anywhere in peritoneal cavity
(Ascitis)
Krukenberg tumor (ovaries)
Sister Joseph nodule
(umbilicus)

Pattern of Nodal Metastases from Gastric Cancer

Clinical Presentation
Most patients present with advanced stage..
why?
They are often asymptomatic in early stages.
Common clinical Presentation:
The patient complained of loss of appetite that was
followed by weight loss of 10Kg in 4 weeks.
He had notice
epigastric discomfort & postprandial fullness.
He presented to the ER complaining of vomiting of
large quantities of undigested food & epigastric
distension.
Dyspepsia
epigastric pain
Bloating
early satiety
nausea & vomiting*
dysphagia*
anorexia
weight loss
upper GI bleeding
(hematemesis, melena,
iron deficiency anemia)

signs
-Anemia.
-Wt.loss ( cachexia)
-Epigastric mass,Hepatomegaly,Ascitis
-Jaundice.
-Blumers shelf
-Virchows node
-Sister mary joseph node
-Krukenberg tumor
-Irish node

• 2011 consensus guidelines
advocate that patients ≥ 55yr with new onset
dyspepsia and
all those with alarm features
should have an urgent (within two weeks)
gastroscopy

“Alarm” features suggestive of gastric
cancer
• New onset dyspepsia in patients >55 years of age
• Family history of UGI cancer
• Unintentional weight loss
• Upper or lower GI bleeding
• Progressive dysphagia
• Iron deficiency anaemia
• Persistent vomiting
• Palpable mass
• Palpable lymph nodes
• Jaundice

Screening
•most successful in high-risk areas.
•A variety of screening tests have been studied in
Japanese patients, with a sensitivity and specificity of
approximately 90%.
•Screening typically includes the use of double-contrast
barium radiographs or upper GI endoscopy.
• In some Japanese studies, up to 60% of patients
actively participating in routine mass screening
programs have the disease and up to 60% of newly
diagnosed patients have Stage I Disease (Early Gastric
Cancer).

•limitations of a mass screening program when the
entire population at risk is not effectively screened.
•
A low serum pepsinogen I/I I ratio used to better
select patients .It increased risk for atrophic gastritis
and gastric cancer.
Pretreatment Staging Tumor Markers
•CEA & CA19-9 levels correlate with depth of tumor
invasion, presence of lymphatic metastasis, extent of
tumor stage and ultimately with patient survival.

•The sensitivity of CEA as a marker of gastric cancer
is low, but when the CEA level is elevated, it generally
correlates with stage.
•Elevated serum Î²-HCG and CA 125 levels in gastric
cancer before chemotherapy may reflect not just
tumor burden but also aggressive biology;
•However, the utility of these markers in staging is
limited.

THE GOLD STANDARD
 It allows taking biopsies
 Safe (in experienced hands)
UGI ENDOSCOPY

EGD esophagogastroduodenoscopy
Diagnostic accuracy is 98%
if upto 7 biopsies is taken.
Double Contrast barium upper GI x-ray
Diagnostic accuracy 90%
WHY?
Diagnostic study of Choice
1.Early superficial gastric mucosal lesion
can be missed.
2. can’t differentiate b/w benign ulcer &
Ulcerating adenocarcinoma.

X-ray showing Gastric ulcer
With symmetrical radiating
Mucosal folds.
By histology, no evidence of
Malignancies was observed.
X-ray showing Extensive
carcinoma involving
the cardia & Fundus
Pyloric stenosis

Diagnosis
• Double contrast barium
swallow has 90%
accuracy and is cost
effective.
– No ability to distinguish
between malignant and
benign ulcers.

Morphology
• Polypoid
• Ulcerative
• Superficial spreading
• Linitis plastica

UGI ENDOSCOPY,contd.
 You may see an ulcer (25%), polypoid mass (25%),
superficial spreading (10%),or infiltrative (linnitis
plastica)-difficult to be detected-
 Accuracy 50-95% it depends on gross
appearance,size,location & no. of biopsies

IF YOU SEE ULCER ASK UR
SELF…BENIGN OR MALIGNANT?
MALIGNANTBENIGN
Irregular outline with
necrotic or hemorrhagic
base
Round to oval punched out
lesion with straight walls &
flat smooth base
Irregular & raised marginsSmooth margins with
normal surrounding
mucosa
AnywhereMostly on lesser curvature
Any sizeMajority<2cm
Prominent & edematous
rugal folds that usually do
not extend to the margins
Normal adjoining rugal
folds that extend to the
margins of the base

T1a
T1b
Depth of tumor
invasion Number of involved LN
Presence or absence of
metastatic disease
TX – Primary tumor
can’t be assessed
T0 – No evidence of
primary tumor
Tis- Carcinoma in situ
Mucosa
Submucosa
Muscularis
propria
Subserosal
CT
Serosa
T3 – gastro-
colic/hepatic lig.,
greater or lesser
omentum

REGIONAL LYMPH NODES (N)
Based on number of LN involved and not the location
 In 1997, nodal classification changed from using the location of the
involved lymph nodes to the number of lymph nodes
pN1, 1–6 nodes
pN2, 7–15 nodes
pN3, >15 nodes
-Requires a minimum of 15 nodes in the resection specimen
-Avrg no. of nodes evaluated - 10, only 30% of pts have at least 15
nodes evaluated

NX - Regional lymph node(s) cannot be assessed
N0 - No regional lymph node metastasis§
N1 - Metastasis in 1-2 regional lymph nodes
N2 - Metastasis in 3-6 regional lymph nodes
N3 - Metastasis in 7 or more regional lymph nodes
N3a - 7-15 nodes
N3b - 16 or more nodes
M0 - No distant metastasis
M1 - Distant metastasis
DISTANT METASTASIS (M)
Because of inadequate nodal evaluation
In the 7th edition of the AJCC classification, a minimum of 7
nodes are required.

TNM Stage
T1 T2 T3 T4a T4b
N0 IA IB IIA IIB IIIB
N1 IB IIA IIB IIIA IIIB
N2 IIA IIB IIIA IIIB IIIC
N3 IIB IIIA IIIB IIIC IIIC

Physical examination
Blood tests
Imaging
Skin changes
Palpable mass
CBC – anaemia
S.E. – GOO
LFT
EUS
CECT

Staging
• 2 major staging systems for gastric carcinoma
– American Joint Committee on Cancer classification
– Japanese Classification of Gastric Carcinoma
• Japanese classification uses T and M staging similar to the
AJCC system
• Nodal staging is significantly different
– The Japanese classification focuses on
• Anatomic location of the nodes, which are designated by
stations

Staging
– AJCC classification
• T stage based on depth of tumor (not size)
• Changes in the 7th edition of AJCC classification
– E-G junction tumors or tumors in the cardia <5cm from
E-G junction extending into E-G junction
• Staged using the TNM staging for esophageal cancer
Rüdiger et al. Ann Surg 2000; 232-353
– Tumors <5cm from E-G junction that don’t extend into
esophagus
• staged as gastric cancers

Staging
– In 1997, nodal classification changed from using the
location of the involved lymph nodes to the number of
lymph nodes (pN1, 1–6 nodes; pN2, 7–15 nodes; pN3,
>15 nodes)
– This requires a minimum of 15 nodes in the resection
specimen
– Avrg no. of nodes evaluated - 10, only 30% of pts have at
least 15 nodes evaluated
Coburn NG et al. Cancer 2006;107(9): 2143–51.
Schwarz RE, Smith DD. Ann Surg Oncol 2007;14(2):317–28.
Smith DD, Schwarz RR, Schwarz RE. J Clin Oncol 2005;23(28):7114–24

Staging
– Because of inadequate nodal evaluation
• In the 7th edition of the AJCC classification, a
minimum of 7 nodes are required (pN1, 1–2 nodes;
pN2, 3–6 nodes; pN3, -7 nodes)
• Comparison of survival
– Using 6th and 7th edition in same population of pts
– Stage stratified survival difference
– This has implications for interpretation and comparison
of outcomes from studies that use 6th vs 7th edition
Warneke VS et al. J Clin Oncol 2011; 29: 2364

Staging
• Recent studies propose examining the metastatic lymph node
ratio (MLR)
– Ratio between metastatic nodes and total evaluated nodes
– More valuable in inadequate node evaluation
– Strongest negative prognostic factors for survival on
multivariate analyses
Persiani R et al. Eur J Surg Oncol 2008;34(5):519–24
Lee SY et al. Int J Oncol 2010;36(6):1461–7.
Sianesi M et al. J Gastrointest Surg 2010;14(4):614–9.

Changes in the 7th edition of AJCC classification
GE junction tumors
or
tumors in the cardia <5cm from GE junction extending
into GE junction
Staged using the TNM staging for esophageal cancer
Rüdiger et al. Ann Surg 2000; 232-353

• Nodal staging is significantly different
– Focuses on Anatomic location of the nodes, which are
designated by stations
– recommendes nodal basin dissection dependent on the
location of the primary

Right
paracardial
Left
paracardial
lesser
curvature
short gastric
left
gastroepiploic
right
gastroepiploic
Suprapyloric
Infrapyloric
left gastric
artery
common hepatic
CELIAC

Splenic
hilum
Proximal & distal
splenic
Hepatoduodenal ligament
-Hepatic artery
-Portal vein
-Bile duct
Posterior of
pancreatic
head
superior mesenteric vein
superior mesenteric artery
15
middle colic
artery and vein
Mesentric
root
Transverse mesocolon

16a1
aortic hiatus
16a2
16b1
16b2
Celiac trunk
Lt. renal vein
Inferior mesentric
artery
20
Esophageal hiatus
No. 17 anterior surface of pancreas head
No. 18 inferior margin on the pancreas
No. 19 Infradiaphragmatic LN

Staging Evaluation
• Once the diagnosis is established, further studies are
directed at staging to assist with therapeutic decisions
• EUS and CT are primary radiological staging
modalities
• Others – MRI, PET scan, laparoscopy

CT scanning and endoscopic ultrasonography (EUS) are complementary.
CT scanning is used first to stage the gastric carcinoma; if no metastases and
no invasion of local organs are found, EUS is used to refine the local stage.
The depth of tumor invasion is not accurately assessed with CT, and the
investigation of choice for this indication is EUS.
Unlike CT and MRI, EUS can depict individual layers of the gastric wall, with
a rotating high-frequency probe

Endoscopy and Endoscopic Ultrasound
(stomach is filled with water)
(biopsy)
– T staging -
The gastric wall is visualized as 5 concentric bands:
Mucosa - Echogenic
Muscularis mucosa - Hypoechoic
Submucosa - Echogenic
Muscularis propria - Hypoechoic
Serosa - Echogenic
– N staging - presence and location of peri-visceral lymph nodes
or detection of malignant cells by EUS guided trans-visceral
FNA
– Less useful for M staging, due to limited depth of penetration
However, with low frequency newer echo-endoscopes, much of the liver can be surveyed
and sampled from the stomach and duodenum
In the future, EUS may play a role in determining those patients who
require further aggressive investigation of metastatic disease (e.g.,
laparoscopy) and those who do not.
gastric tumor -
hypoechoic mass

Staging Evaluation
– Accuracy for T staging - 64%
Bhandari S et al. Gastrointest Endosc 2004;59:619-26
– Sensitivity for N staging – 70 to 100%
EUS image of T1 cancer. Thick dark arrow demonstrates
mucosal tumor invading the broad white layer of
hyperechoic submucosa (white arrow) but not disrupting
the dark layer (hypoechoic) of the muscularis propria
(thin dark arrow)

• CT scan
– Useful in identifying distant metastases, especially in the liver
Paramo JC et al. Ann Surg Oncol1999;6:379-84
Davies J et al. Gut 1997;41:314-9
CT demonstrates T4 gastric carcinoma of proximal body
with extension into perigastric fat and involvement of
splenic artery

Computed Tomography
• useful for M staging
- primary method for detection of intra-
abdominal metastatic disease, with an overall
detection rate of approximately 85%.
For detecting SENSITIVITY SPECIFICITY
Liver metastasis 75% 99%
Peritoneal
metastasis
33% 95%

T staging and N staging –
 The accuracy of T and N stages as determined
by CT is less accurate than EUS.
Sabiston textbook of surgery 19th ed.
Paramo JC et al. Ann Surg Oncol1999;6:379-84
Irving, recent advances in surgery.
 CT and MRI are not useful in distinguishing
between enlarged nodes due to reactive
changes and those due to tumor.

Staging Evaluation
• MRI
– When CT iodinated contrast is contraindicated
– For T staging, MR is comparable or minimally superior to CT
Sohn KM et al. AJR Am J Roentgenol 2000;174:1551-7
– Improvement in detection of metastatic disease compared with
CT, when the contrast Ferumoxtran-10 is used (sensitivity 100%)
Coburn NG. J Surg Oncol 2009;99(4):199–206
Motohara T, Semelka RC. Abdom Imaging 2002;27(4):376–83

MRI
When CT iodinated contrast is contraindicated
• For T staging, MR is comparable or minimally superior to CT
Sohn KM et al. AJR Am J Roentgenol 2000;174:1551-7
• Inferior to CT in N staging
• M staging - Improvement in detection of metastatic disease
compared with CT, when the contrast Ferumoxtran-10 is used
(sensitivity 100%)
Coburn NG. J Surg Oncol 2009;99(4):199–206
Motohara T, Semelka RC. Abdom Imaging 2002;27(4):376–83

PET scan
• not currently a primary staging modality.
• Only 50% gastric cancers are PET-avid
• PET response to neoadjuvant therapy seen after 14 days of
treatment strongly correlates with survival, therefore for
monitoring response to these therapies, sparing unresponsive
patients further toxic treatment

Staging Evaluation
• PET
– Useful in staging, recurrence detection and measuring therapy
response
– Detect node metastases before nodes are enlarged on CT
– Sensitivity for nodal staging – 23 to 73%
Yoshioka T et al. J Nucl Med 2003;44:690-9
– Limitations
• False +ve results from infectious or inflammatory processes
• Lower sensitivity for small lesions

Staging Evaluation
– High FDG uptake
• Associated with greater depth of invasion, size of tumor and
lymph node metastases
• Significantly lower survival rate
Mochiki E et al. World J Surg 2004;28:247-53
– Combined PET and CT (PET/CT)
• Recently introduced
• Perform both a PET and CT scan in the same session and
fuse the images.
• Excellent contrast resolution of PET
• Excellent spatial resolution of CT.
• Improved accuracy of PET/CT compared with PET alone
Antoch G et al. J Clin Oncol 2004 1;22:4357-68

Staging Evaluation
• Laparoscopy
– In 1985, report by Shandall and Johnson
• Detection of metastatic disease to the liver or peritoneum
• Sensitivity - 100%, specificity - 84%
• Avoidance of laparotomies - 29% of pts
– Now nodal staging is possible with laparoscopic ultrasound
– NCCN recommend laparoscoy in loco-regional gastric cancer
(M0) to guide further management
Jaffer A et al. http://www.nccn.org, v.1.2006

Staging Evaluation
– Implications
• In resectable pts for staging
• In unresectable pts – determination of benefits of combined
chemo-radiation (radiation may not be appropriate in
metastatic disease)
Jaffer A et al. http://www.nccn.org, v.1.2006
• Staging before entry into neo-adjuvant trials
D’Ugo DM et al. J Am Coll Surg 2003;196:965-74
– Not necessary in T1 or T2 lesions given the low incidence of
metastases
– Not indicated in the pre-op evaluation of gastric remnant
cancers, since they do not tend to develop peritonea metastasis.

classification of Esophagogastric Junction Cancers
•Siewert classification, this system recognizes three
distinct clinical entities that arise within 5 cm of the
junction of the tubular esophagus and the stomach:
•Type 1—adenocarcinoma of the distal esophagus,
which usually
-arises from an area with specialized intestinal
metaplasia of the esophagus (i.e., Barrett's
esophagus) and may infiltrate the esophagogastric
junction from above.

•Type 2-adenocarcinoma of the cardia, which arises
from the epithelium of the cardia or from short
segments with intestinal metaplasia at the
esophagogastric junction.
Type 3 -adenocarcinoma of the subcardial stomach,
which may infiltrate the esophagogastric junction or
the distal esophagus from below.
•The assignment of tumors to one of these subtypes is
based on morphology and the anatomic location of the
epicenter of the tumor.

•Classification can be performed based on the results of
contrast radiography, endoscopy, CT and operative
findings.
•The Siewert classification has important therapeutic
implications.
•
The lymphatic drainage routes differ for type 1 versus
type II and III lesion.
•The lymphatic pathways from the lower esophagus pass
cephalic (into the mediastinum) and caudal (toward the
celiac axis).
•In contrast, the lymphatic drainage from the cardia and
subcardial regions is toward the celiac axis, splenic
hilum, and paraaortic nodes.

•Thus, the Siewert classification provides a practical
means for choosing among surgical options.
•For type I tumors, esophagectomy is required,
whereas type II and in 111 tumors can be treated by
transabdominal extended gastrectomy.
(resection of the stomach and distal intraabdominal
esophagus).

SURGICAL THERAPY – the only prospective of cure
Objective : Complete resection of gastric tumor with a wide (≥6cm) margin
what is R status ?
Describes tumor status after resection
• R0 – microscopically margin-negative resection.
• R1 – macroscopic clearance of tumour but microscopic margins are positive.
• R2 – gross residual disease.
…Hermanek, 1994

Total gastrectomy should not as a routine procedure for gastric
adenocarcinoma.
Patients in whom R0 resection can be obtained, a more limited gastric
resection (e.g., proximal esophagogastrectomy or distal subtotal gastrectomy)
provides the same survival result less perioperative morbidity.
Surgery
Endoscopic
sub-mucosal
resection
Hemi-
gastrectomy
Subtotal
gastrectomy
Total
gastrectomy

Surgery
• Best chance for long-term survival - complete surgical
eradication of a tumor with resection of adjacent nodes
• 6 factors determine the extent of gastric resection
– Tumor stage
– Tumor histology or type
– Tumor location
– Nodal drainage
– Peri-operative morbidity
– Long-term gastro-intestinal function

Surgery
• Indications for unresectability
– Distant metastases
– Invasion of a major vascular structure such as the aorta
– Encasement or occlusion of the hepatic artery or celiac
axis/proximal splenic artery
– Nodes behind or inferior to the pancreas, aorto-caval region, into
the mediastinum, or in the porta hepatis
• Distal splenic artery involvement is not an indicator of
unresectability

EMR and ESR
EMR (Endoscopic mucosal resection)
injection of a substance under the targeted lesion to act as a cushion,
lesion is then removed with a snare or suctioned into a cap and snared
.
ESR (Endoscopic sub-mucosal resection)
injection of a substance under the targeted lesion to act as a cushion,
submucosa is instead dissected under the lesion with a specialized knife.
This enables removal of larger and potentially deeper lesions
 higher rates of R0 resections and a lower rate of local recurrence, but
 technically demanding and has more adverse events.

• Tumor resection techniques
– Anterior wall tumors
• Sub-mucosal tumors – stapled wedge resection
• Large extra- or intra-luminal tumors
• Ultrasonic shears are used to excise the tumor
• Requires the closure of a large gastrotomy

– Posterior wall tumors
• Small intra-luminal or larger extra-luminal tumors
• Stapled wedge resection
• Division of the short gastric vessels is required
• Larger intra-luminal tumors
• Requires anterior gastrostomy

• Small intra-luminal tumors close to the lesser
curvature
• Percutaneous intra-gastric technique

Disadvantage
Incomplete resection d/t large tumor size or unrecognised LN metastasis
A Japanese study
N = 5000
• small tumors, regardless of ulcer status, and
• nonulcerated tumors, regardless of size,
did not have associated lymph node disease.
patients with submucosal invasion less than 500 μm behaved similarly to
patients who had completely intramucosal
tumors.
Guidelines for ESR
 All intramucosal tumors (any size) without ulceration
 Differentiated mucosal tumors of <3cm, with/without ulceration
 Limited submucosal invasion with size <3cm & without ulceration

Distal 1/3rd tumor :
Distal gastrectomy
Hemigastrectomy
Subtotal gastrectomy
Middle 1/3rd tumor :
 Subtotal gastrectomy
 Total gastrectomy

Proximal 1/3rd tumor :
 Proximal esophago-gastrectomy (if R0 resection possible) but l/t
symtomatic reflux
 Total gastrectomy

– Gastric cancers within the proximal stomach
• Worse prognosis
• Harrison conducted retrospective study
– 391 pts
– To determine whether the type of operation (TG vs PSG)
affects outcome
– Excluded pts who underwent esophago-gastrectomy
– No significant difference in the 5-year survival (41 vs
43%)
– Conclusion
• PSG with adequate –ve margins is oncologically
acceptable
Harrison LE et al. Surgery 1998;123(2):127–30

• TG is preferred by some surgeons because
– Extremely low incidence of reflux esophagitis
• Roux-en-Y reconstruction performed during TG
compared to PSG
Buhl K et al. Eur J Surg Oncol 1990; 16:404

Extent of lymph node dissection
 D1
Perigastric nodes (station 1-6)
Conservative node dissection
 D2
D1 + left gastric, Common hepatic,celiac & splenic L.N.(7-11)
Extended node dissection
 D3
D2 + Hepato-duodenal ligament, retropancreatic & mesenteric root (12-16)
Super-extended lymphadenectomy
 D4
D3 + para-aortic and para colic LN dissection

– Extended lymphadenectomy (D2 to D4)
• Performed by most of Japanese surgeons
• Removal of larger number of nodes
– Greater the probability of positive nodes
– More accurately stages disease extent
– Minimize stage migration (the “Okie phenomenon”,
described by Will Rodgers)
– Explain better survival results in Asian patients
Bunt AM et al. J Clin Oncol 1995; 13:19.37
de Manzoni G et al. Br J Cancer 2002; 87:171

– Two main arguments against the routine use of an extended
lymphadenectomy
• Higher morbidity and mortality
• Lack of a survival benefit in most large randomized trials
– Medical Research Council (MRC) trial
• Prospective randomized trial
• 400 pts undergoing curative resection to D1 or D2
lymphadenectomy
• Coclusion
– Postoperative morbidity was significantly greater in the
D2 group - 46 vs28%, operative mortality - 13 vs 6%
– Due to splenectomy and distal pancreatectomy to achieve
complete node dissection
Cuschieri A et al. Lancet 1996; 347:995

Extent of nodal dissection D1 v/s D2
most controversial area in gastric cancer management
Non japanese literature
D2 lymphadenectomy, when compared with a D1 dissection, has increased surgical
morbidity, without a benefit in survival.
One criticism of the Western data is that although randomized, the D2 group did not
differentiate between patients who had a splenectomy and those who did not.
Subsequent subgroup analysis of the D2 without splenectomy group has shown
results similar to the Japanese studies, with increased survival and no significant
increase in morbidity.
Japanese literature
Increased survival in patients undergoing a D2 dissection, with no increased or
minimal increase in morbidity.

Resectable or not ?
 Involvement of other organ per se does not imply incurability, provided that it
can be removed ….Bailey and love’s short practice of surgery 26th ed.
 Therapeutic nihilism should be avoided &, in low risk patient, an aggressive
attempt to resect all tumor should be made. The primary tumor may be resected en
bloc with adjacent involved organs (eg., pancreas, transverse colon, or spleen)
……Schwartz’Princilpes of Surgery 10th ed.
 A solitary metastatic nodule in liver is also no indication against curable
resection.
..(CSDT) Current Diadnosis and Treatment, Surgery 14th ed.

Steps in Total gastrectomy
Long mid-line incision or b/l subcostal incision (chevron)
Detachment of greater omentum from
colon
anterior layer of mesocolon is dissected
from mesocolonic vessels
Dissect upto inferior border of
pancreas and divide Rt GE vessels
Dissect upto splenic hilum, ligate Lt.
GE & short gastric
dissect lesser omentum
from the undersurface
of the Liver extending
back to the right crus
and mobilizing the right
aspect of G-E junction.
Divide duodenum with GIA stapler

close the duodenal stump with
interrupted horizontal 3-0 absorbable
mattress sutures, essentially
"dunking“ the duodenum.
Dissection of porta, hepatic artery, &
celiac axis is completed from above
down
Left gastric artery divided at its
origin f/b clearance of right crus
and celiac axis
dissection of all the tissue from
Lt. crus & paracardial LNs
Mobilization of esophageal
hiatus by detaching the
peritoneal reflection from
the diaphragm
Divide esophogus sharply by knife
or scissors

Steps in Subotal gastrectomy
1) Mobilization of the greater curvature
with omentectomy & division of left
gastroepiploic vessels
2) lnfrapyloric mobilization with
ligation of the right gastroepiploic
vessels
3) Suprapyloric mobilization with
ligation of the right gastric vessels
4) Duodenal transection
5) D2 lymphadenectomy, with
dissection of the porta hepatis,
common hepatic artery, left gastric
artery, celiac axis, & splenic artery,
and ligation of left gastric vessels
6) Gastric transection

Peri-operative Chemotherapy
 MAGIC trial
Randomised controlled study of 503 pts. With stage II or higher gastric cancer that
compared perioperative chemotherapy with surgery alone.
CEF (Cisplatin, Epirubicin, 5-FU) - 3 cycles as neo-adjuvent CT
- 3 cycles as adjuvent CT
5-yr survival, rate of local recurrence & distant metastasis were improved in CT
group
 UK National Cancer Institute trial
OEX (Oxaliplatin, Epirubicin, Capecitabine)
longer overall survival than with CEF and decreased incidence of thromboembolic
phenomenon by substituting oxaliplatin for cisplatin

Intraperitoneal Chemotherapy (IPC)
 Recurrence following curative resection is likely due to peritoneal
carcinomatosis.
 Systemic CT : blood-peritoneal barrier prevents the chemotherapeutic agents
from achieving their cytotoxic effect.
 IPC : administering high doses of chemotherapy directly to the peritoneum
whilst reducing the systemic effects.
 HIPC (hypothermia Intraperitoneal Chemotherapy )
 increased risk of neutropaenia and intra-abdominal abscesses.

Adjuvent Radiotherapy
INT(0116) trial demonstrates improvement in DFS and OS with post-operative
chemoradiation than with surgery alone.
Radiotherapy is limited, due to its position near vital organs like kidney spinal cord,
pancreas, liver & bowel.
Stomach itself is highly sensitive, tends to bleed and ulcerate with EBRT.
Intraoperative radiotherapy (IORT)
Takahashi & Abe in 1986, Japan randomized 211 patient IORT (25- 40 Gy) Vs
surgery alone claims ↑ in 5-yr SR with IORT.
Chen & Song 1994, China randomized stage 3 & 4 patients for surgery with IORT
Vs surgery alone claims ↑ in SR only in stage 3.
Sindelar & Tepper et al in 1993 , NCI (National Cancer institute) claims no survival
benefit with IORT, but improvement in local recurrence (44% Vs 92%, p < 0.001).
Still it needs to define the role of IORT in gastric carcinoma.

Reconstruction after surgery
After total gastrectomy  Roux-en-Y esophago-jejunostomy
Division of jejunum with GIA
stapler
end-to-side esopago-
jejunostomy

full-thickness running
suture
Placement of the
EEA stapler through
the divided loop
Completion of the stapled anastomosis
and closure of the end of the loop with
a stapler.
 Jejunal loop should be at least 40 cm from the subsequent jejunojejunal anastomosis to
minimize esophageal reflux.

Alternative reconstruction with
the EEA stapler using a separate
enrerotomy and end-to-end
anastamosis
Jejunal pouch / Omega pouch
Pouch creation can be done safely without increased
morbidity or mortality without significantly increasing the
operative time.
QOL was significantly better in pts with pouch
reconstruction.
Gertler R et al. Am J Gastroenterol 2009; 104(11):2838–51
make the pouch first by two passages of the GIA
stapler and then perform the Esophago-jejunal
anastomosis

Completed Roux-en-Y reconstruction
Post-op :
Unless fever or ileus develops, the patient is
allowed ice on the 1st day and can be given
nutrient by the 5th day.
Any concern clinically for anastomotic leak can
be confirmed by a Gastrografin Swallow, which
is not routine

After Subtotal gastrectomy  Loop gastro-jejunostomy (Bilroth II) or
Roux-en-Y gastrojejunostomy
Stomach divided at greater curvature for 6-8 cm by knife (site of future
anastamosis) and then completely divided with GIA stapler
Staple line inverted with
suture
Anticolic Bilroth II
Retrocolic Bilroth II
Bilroth II

Standard technique for a two-layer, hand-sewn gastrojejunal anastomosis
After placement of corner
sutures, a back row of interrupted
3-0 silk Lembert sutures is
placed
jejunostomy is made with
cautery
inner layer anastomosis
is constructed in running, full-
thickness fashion with 3-0 PDS
Anterior
row of
interrupted
3-0 silk
Lembert
sutures

After Subtotal gastrectomy  Roux-en-Y gastrojejunostomy
jejunum is divided with GIA
stapler approx. 20cm distal to
the ligament of Treitz
end-to-side Roux-en-Y
gastrojejunostomy is created
with a Roux limb at least
45cm in length to avoid
reflux

• Reconstruction following TG
– Most common option
• E-S esophago-jejunostomy with distal drainage of the
duodenum by Roux-en-Y entero-enterostomy
– Meta-analysis by Gertler
• Review from 13 randomized control trials
• Assessed the value of jejunal S-pouch formation as a gastric
substitute after TG.
• Conclusion
– Pouch creation can be done safely without increased
morbidity or mortality without significantly increasing
the operative time or LOS. QOL was significantly better
in pts with pouch reconstruction
Gertler R et al. Am J Gastroenterol 2009; 104(11):2838–51

• Advanced procedures
– Laparoscopic resection
• Meta-analysis of 5 randomized trials and18 non-randomized
comparisons of laparoscopic versus open gastrectomy came
to following conclusions
– Mean number of lymph nodes retrieved by laparoscopic
surgery was close to that retrieved by open procedure
– Conversion rate – 0 – 3%
– Significantly less postoperative morbidity after a
laparoscopic procedure
– No difference in long term survival

• In the revised Japanese Gastric Cancer Treatment Guidelines
– Laparoscopy-assisted gastrectomy -eligible for stage IA
and IB cancers.
Kodera Y et al. J Am Coll Surg 2010; 211(5):677–86
• Laparoscopic gastrectomy with D2 lymphadenectomy
– Performed safely
– Less blood loss
– Lengthier operative times
Tanimura S et al. Surg Endosc 2008; 22(5):1161–4.
Kawamura H et al. World J Surg 2008;32(11):2366–70

Laparoscopic resection
Meta-analysis of 5 randomized trials and 18 non –randomized comparisons of
laparoscopic versus open gastrectomy came to following conclusions
 Mean number of lymph nodes retrieved by laparoscopic surgery was
close to that retrieved by open procedure
 Less blood loss
 Lengthier operative times
 Conversion rate – 0 – 3%
 Significantly less postoperative morbidity after a laparoscopic procedure
 No difference in long term survival
Tanimura S et al. Surg Endosc 2008; 22(5):1161–4.
Kawamura H et al. World J Surg 2008;32(11):2366–70
Revised Japanese Gastric Cancer Treatment Guidelines
Laparoscopy-assisted gastrectomy eligible for - stage IA and IB (T1N1,
T2N0) cancers.
Kodera Y et al. J Am Coll Surg 2010; 211(5):677–86

Robot assisted Surgery
Robot assisted surgery (RAS)
Advantages
• Provides articulated movement
• Eliminates physiologic tremor
• Steady camera platform allows more precise instrument
movement and dissections
Song J et al. Ann Surg 2009;249(6):927–32

– Gastric cancers within the distal stomach
• Bozzetti conducted randomized trial
– 618 pts
– Evaluation of impact of SG vs TG on the oncologic
outcome
– Conclusion
• Both procedures have a similar survival probability
• SG associated with a better nutritional status and
quality of life provided that the proximal margin falls
in healthy tissue
Bozzetti F et al. Ann Surg 1999; 230:170

• Gouzi conducted multi-centric post-operative controlled trial
– 169 pts
– Postoperative mortality and the 5-year survival were
compared for adenocarcinoma of antrum
– Conclusion
• TG - overall complication - 32 %, peri-operative
mortality rates - 1.3%
• SG – overall complication - 34% , peri-operative
mortality rates - 3.2%
• No difference in the 5-year survival rate (48%)
Gouzi JL et al. Ann Surg 1989; 209:162

– Mid-gastric lesions or infiltrative disease (linitis plastica)
• Nodal involvement is frequent
• May require TG for complete excision

• Extended resection for T4 disease
– Multi-organ resections - frequently indicated in T4 disease
– Assessment of adjacent organ invasion by preoperative CT or
intra-operative assessment is unreliable
– Series by Sandler
• 21 pts undergoing multi-organ resections
• only 8 (38%) had pathologically confirmed T4 disease
• Preoperative CT is inaccurate in assessing T4 lesions, with a
positive predictive value of only 50%
Sandler RS et al. Dig Dis Sci 1984;29:703-8

– Recent studies suggest that 5-year survival rates may be as low
as 16%
Kunisaki C et al. J Am Coll Surg 2006;202:223-30
– Regardless, it can be performed with little increased morbidity
with the expectation that long-term survival is possible in
approximately one third of patients with RO resections.

• Extent of nodal dissection
– Lymph node involvement - most important independent
prognostic factors
– Japanese first reported cohort studies - disease-free and overall
survival is increased with radical lymphadenectomies
Inada T et al. Anticancer Res 2002;22:291-4.
– Appropriate extent of nodal dissection - most controversial area
in gastric cancer management

• Surgery based on tumor location
– Bulky tumor fixed to the pancreatic head
• High risk for occult metastatic disease
• Consider staging laparoscopy or neo-adjuvant chemotherapy
• Might require Whipple’s procedure

– Robot assisted surgery (RAS)
• Advantages
– Provides articulated movement
– Eliminates physiologic tremor
– Steady camera platform allows more precise instrument
movement and dissections
Song J et al. Ann Surg 2009;249(6):927–32
• Series by Song
– 100 pts with early gastric cancer
– Robot-assisted gastrectomy, using the da Vinci Surgical
System
– TG – 33, SG – 67 (with D1 dissection)

Treatment of Advanced Disease (StageIV)
Palliative Systemic Chemotherapy versus Best
Supportive Care
As is the case for other solid tumors, the modest activity
and substantial toxicity of cytotoxic chemotherapy raised
the question as to whether palliative use of the available
agents was worth it, that is, there was controversy as to
whether or not there was an advantage to early initiation
of systemic therapy versus best supportive care.

•Wagner et al. performed a meta-analysis for the Cochran
collaboration of several of these studies.
•Patients receiving chemotherapy as part of their treatment
had a better overall survival than those receiving best
supportive care only, with an overall HR of 0.39 .
•The median survival was improved from 4.3 months for
best supportive care to approximately 11 months for
chemotherapy.
•Wagner et al. concluded that the evidence supporting
initiating chemotherapy for patients with advanced
incurable gastric cancer was convincing.

•The average quality-adjusted survival for chemotherapy
patients was superior to best supportive care patients (6
months vs. 12 months).
Single-Agent Chemotherapy
•Fluorouracil -parent fluorinated pyrimidine.
•One method involved the use of rapid intravenous
injections on a weekly basis or daily for 5 consecutive
days.
•the major toxicities reported ---are mucositis, diarrhea, or
mild myelosuppression.

•Because continuous intravenous infusion schedules
can be cumbersome, oral analogs of 5-FU have been
studied in gastric cancer.
•. These are UFT (tegafur and uracil),
• S1 (tegafur and two modulators, 5-chloro-2,4-
dihydroxypyridine and potassium oxonate), and
• capecitabine

•Platinum compounds, --cisplatin
response rate of approximately 15% was reported.
toxicities --are nausea and vomiting, peripheral
neuropathy, ototoxicity, and nephropathy.
•Taxanes --paclitaxel and docetaxel
•The overall response rate was 19.1%.
• toxicities ---neutropenia, alopecia, and edema.
Allergic reactions were seen in about 25% of patients.
• The most common doses schedule was docetaxel
100 mg/m2
every 3 weeks.

•Irinotecan -Both as a single agent and in
combination.
When used alone, response rates of 15% to 25% have
been reported in both previously treated and untreated
patients.
The major toxicities of irinotecan are
myelosuppression and diarrhea.
•Anthracyclines
response rate for doxorubicin of 17%, and for
epirubicin 19%.

Single-Agent versus Combination
Chemotherapy
•In the recent Cochrane review.
•The difference in average survival, however, was quite
modest, 7 months for combination chemotherapy
versus slightly less than 6 months for single agents.
•Wagner et al. found that including anthracyclines in a
fluorouracil-cisplatin combination had a modest
advantage over cisplatin-fluorouracil alone.
•Oxaliplatin and capecitabine are also being used in
combination chemotherapy,

Combination Chemotherapy
•Cisplatin-Fluorouracil
•One of the most widely used.
• Cycles were given on an every 28-day basis.
•Major objective tumor regression was reported in 20% to
30% of patients.
-Median survival ranging from 7.2 to 8.6 months.
-Two-year survival was between 7% and 10%.

Docetaxel, Cisplatin, and Fluorouracil
•The median time to progression was 3.7 months for
patients receiving cisplatin-fluorouracil, and 5.6 months
for those receiving DCF.
•Survival was also modestly increased from 8.6 months
for cisplatin-fluorouracil to 9.2 months for DCF.
•The 2-year survival rate was, however, more than
doubled for DCF (8.8% for cisplatin-fluorouracil and
18.4% for DCF).

Epirubicin, Cisplatin, and Fluorouracil
•ECF was more effective both in terms of response rate and
for median survival 8.7 months .
• Two-year survival 14%.
•Median duration of survival -9.4 months
•1-year survival 40%.
Cisplatin Plus Irinotecan
•Response rates were encouraging, and toxicity was
tolerable.
Fluorouracil-Leucovorin-Oxaliplatin
•Overall response rates of approximately 50% were
reported.
- median overall survival of 10 to 12 months.

Targeted Therapy
•Bevacizumab
A humanized monoclonal antibody that binds the
vascular endothelial growth factor ligand.
Shah et al. have reported the results of a phase II to study
combining cisplatin plus irinotecan with Bevacizumab.
Bevacizumab was given at 15 mg/kg on a once every 3-
week basis.
Concluded that Bevacizumab could safely be given with
cytotoxic chemotherapy, including in patients in whom the
primary tumor was still in place.
Cancer: Principles and Practice of Oncology 6th edition (July 2001): by Vincent T. Devita
(Editor), Samuel Hellman, Steven A. Rosenberg (Editor) By Lippincott

Epidermal Growth Factor
Receptor Tyrosine Kinase
Inhibitors
Erlotinib and gefitinib
Modest single agent activity has
been reported.
Cetuximab, an antibody to the
epidermal growth factor receptor,
is undergoing study as a single
agent and also in combination
with systemic cytotoxic
chemotherapy.

Surgery for Palliation
•Because the survival for patients with advanced gastric
cancer is so poor, any proposed operation should have a
good chance of providing sustained symptomatic relief
while minimizing the attendant morbidity and need for
prolonged hospitalization.
•Resection may provide palliation of symptoms; however,
survival after total gastrectomy is exceedingly poor,
ranging from 3 months to 1yr.

•Once amenable only to open GJ,distal obstructions
may now be alleviated by the endoscopic placement
of self expanding endoluminal stents.Such stents
are effective in upto 85% of patients,with an
uninterrupted duration of function of 5-6months.
•Thus, whenever possible,patients who have Ml
disease should be approached by nonoperative
means.

Radiation for Palliation
•To date, no studies have evaluated the use of
radiation therapy in patients with locally recurrent or
metastatic carcinoma.
•Its use is limited to palliation of symtoms such as
bleeding or controlling pain secondary to local tumor.
s

Gastric Lymphoma
Epidemiology
•The stomach is the most common site of lymphomas in
the GI system.
•Primary gastric lymphoma is still relatively uncommon,
accounting for less than 15% of gastric malignancies and
2% of lymphomas.
•Patients often present with vague symptoms, namely
epigastric pain,early satiety, and fatigue.
•Constitutional B symptoms are very rare.
Primary gastric lymphoma Ahmad M Al-AkwaaNeelam Siddiquiand Ibrahim A Al-Mofleh

•peak incidence in the sixth and seventh decades, and
are more common in men(male-to-female ratio of 2:1).
•most commonly occur in the gastric antrum but can
arise from any part of the stomach.
Pathology
•In the management of gastric lymphomas,
it is important to determine not only the stage of
disease but also the subtype of lymphoma.

•The most common gastric lymphoma is diffuse large B-
cell lymphoma (55%),
extranodal marginal cell lymphoma (MALT)(40%),
Burkitt's lymphoma 3%), and
 mantle cell and follicular lymphomas (each <1%).
• MALT lymphoma were recently reclassified as extranodal
marginal zone lymphomas of MALT-type.
most commonly preceded by H-pylori associated gastritis.

Evaluation
•Endoscopy generally reveals nonspecific gastritis or
gastric ulcerations, with mass lesions being unusual.
•Endoscopic ultrasound is useful to determine the
depth of gastric wall invasion, specifically to identify
patients at risk for perforation secondary to full-
thickness involvement of the gastric wall.

•Evidence of distant disease should be sought
through upper airway examination, bone marrow
biopsy, and CT of the chest and abdomen to detect
lymphadenopathy.
•Any enlarged lymph nodes should undergo biopsy.
H. pylori testing should be performed.

Staging Systems for Primary Gastrointestinal
Non-Hodgkin’s Lymphoma
Staging
•Best Staging remains controversial

Treatment
•Most centers employ a multimodality treatment
program for patients with gastric lymphoma.
•The role of resection in gastric lymphoma remains
controversial,
• Many patients are now being treated with
chemoradiation therapy alone.
•The most common chemotheraphy combination is
CHOP(cyclophospamide, doxorubicin vincristine and
prednisalone) .
•Radiation therapy is limited in usefulness for larger
tumors with local complications of radiation therapy,
such as stricture,enteritis, and secondary tumor
formation.

•The diagnosis of lymphoma discovered
unexpectedly at operation can be confirmed by frozen
section. Additionally, fresh tissue should be sent for
flurescence-activated cell sorting,
immunohistochemistry and genetic analysis.
•If isolated stage IE or 11E lymphoma is encountered,
surgical removal of all gross disease is ideal.

•Recent evidence suggests that early-stage MALT
lymphomas as well as some cases of very limited
diffuse large B-cell lymphoma may be effectively
treated by H-pylori eradication alone.
•Successful eradication resulted in remission in more
than 75% of cases. However, careful follow-up is
necessary, with repeat endoscopy in -2 months to
document clearance of the infection as well as
biannual endoscopy for 3 years to document
regression.

•The presence of transmural tumor extension,
nodal involvement,
transformation into a large cell phenotype,t(ll;18),
 or nuclear BCL-10 expression all predict failure after
H. pylori eradication alone.
•A small subset of MALT lymphoma patients are H-
pylori negative.
In these patients, consideration should be given to
surgical resection, radiation, and chemotherapy.
•The 5-year disease-free survival rate with
multimodality treatment is greater than 95% in stage IE
and 75% in stage 11E disease.

Gastric Carcinoids
•Gastric carcinoids constitute up to 5% of all carcinoids
•Gastric carcinoids arise from enterochromaffin-like cells
of the fundus of the stomach.
•Commonly discovered as an incidental finding during the
workup for other symptoms, when a yellow nodule is found
in the fundus of the stomach.

•Patients may complain of histamine-producing
symptoms, such as cutaneous flushing,
bronchospasm, itching, and lacrimation.
•Diagnosed by gastric biopsy,
histologic chromogranin,
features of dysplasia,
 mucosal atrophy, and the degree of mucosal invasion
diagnosed by both biochemical and histologic means.
• Upper gastrointestinal endoscopy, including EUS, is
also essential to evaluate the number, size, extent, and
location of lesions.

•CT of the abdomen is essential to exclude metastasis
to the liver and nodal involvement.
Treatment
•For patients with either type I or II carcinoids, and
with tumors less than 1 cm or with fewer than three to
five lesions, -endoscopic polypectomy or endoscopic
mucosal resection, with endoscopic surveillance every
6 months.

•Type III disease should be considered for en bloc
resection with lymphadenectomy, depending on the tumor
size, although the high incidence of hepatic metastasis
should tamper this decision.
•5-year survival rates -type I or II 60% and 75%.
-type III less than 50%.
•Follow-up
-consists of plasma chromogranin determinations.
Plasma gastrin
-urinary 5-hydroxyindoleacetic acid (5-HIAA) less
sensitive.

•GISTs are the most common mesenchymal tumors of the stomach
•Stomach being the most common location (40%),
small intestine (32%).
•Predominantly found in males, median age at diagnosis of 63 years.
• The presenting features varied --- include bleeding (38%), abdominal
pain (11.8%), and rupture (1%); 12% of patients have no symptoms.
• The median size 6 cm.
•Regardless of the location of these tumors in the stomach, R0
resection remains the treatment of choice,
•Tumor size (>5 cm) and mitotic index (>5/50 hpf), are associated with
a less favorable prognosis.
Giant gastrointestinal stromal tumor (GIST) of the stomach cause of high bowel obstruction: surgical management
Alessandro Cappellani,Gaetano PiccoloEmail author,Francesco Cardì,Andrea Cavallaro,Emanuele Lo
Menzo,Vincenzo Cavallaro,Antonio Zanghì,Maria Di Vita and
Massimiliano Berretta
World Journal of Surgical Oncology201311:172
Gastric Intestinal Stromal Tumors of the Stomach

The origion: Intestinal Cells of Cajal ‘ICC;s’ autonomic nervous
system.
The distinction bw benign & malignant is unclear. In general terms,
the larger the tumor & greater mitotic activity, the more likely to
metastases.

• Tumor location in the
-gastroesophageal junction or fundus,
-ulceration,
-coagulative necrosis, and
- mucosal invasion ------ poor outcome.
• Antral tumors and with unresectable or metastatic
disease are offered treatment with Imatinib ( an oral
tyrosine kinase inhibitor).
• They may then be re-evaluated for potential resection if
they demonstrate response to treatment.

Summary
• 6 cm margin clearance of tumour is recommended.
• D2 lymphadenectomy is essential.
• Resection of greater & lesser omentum is necessary.
• Splenopancreatectomy only on indicated cases.
• For proximal lesion varying length of esophagus
should be excised.
• Judicious decision should be taken for total, proximal
& distal gastrectomy.
• All patient should receive chemoradiation.

Summary
• EUS and CT are primary staging modalities
• PET useful in staging, recurrence detection and measuring therapy
response
• Laparoscoy useful in loco-regional gastric cancer (M0) to guide
further management
• Japanese classification focuses on anatomic location of the
nodes(designated by stations)
• In AJCC classification nodal stage is based on number of involved
nodes
• Proximal gastric cancers – TG preferred because of less incidence
complication

Summary
• Distal gastric tumors – SG preferred
• Assessment of adjacent organ invasion by preoperative CT or intra-operative
assessment is unreliable
• Extended lymphadenectomy (D2 to D4)
• More accurately stages disease extent
• Explain better survival results in Asian patients
• Higher morbidity and mortality
• Lack of a survival benefit in most large randomized trials
• QOL was significantly better in pts with pouch reconstruction
• Gastrostomy and jejunostomy - little role in gastric cancer

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