Gastric CA by Dr. Aregawi Kassa

Management Of Gastric Cancer
Aregawi kassa , MD
11/01/2012 G.C
MU-CHS
11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 1

Introduction
Described as early as 3000BC
Most common & lethal cancer

2nd most common killer of all malignancies
Significant geographical , ethnic & socio-

economic differences in distribution
Highest in Eastern Asia, South America &
Eastern Europe

Remains to be a difficult Disease to cure
Late presentation & advanced Disease
High recurrence even if resected
Decrease incidence and mortality rates for gastric

CA during past 75 years
A decline in the intestinal type compared with
the diffuse type
Recognition of some risk factors
Popularization of refrigerators

Pathogenesis of Gastric Ca
According to Laurens classification

2 distinct types of Gastric Ca
A. Intestinal Type (Well differentiated)
B. Diffuse Type (Un differentiated)
Both have
Distinct morphologic appearance,
Pathogenesis &
Genetic profiles

Premalignant lesions
For Intestinal type

Chronic Gastritis/Chronic atrophic gastritis
(hypochlorohydria/Achlorohydria)
Intestinal metaplasia
Dysplasia (Low or High grades)
Adenocarcinoma
Risk factors

a major cause of stomach cancer, especially cancers in the
lower (distal) part of the stomach.
H. Pylori may lead to inflammation (chronic atrophic gastritis) and
infection pre-cancerous changes of the inner lining of the stomach
Stomach cancer is more common in men than in women.

Gender
There is a sharp increase in stomach cancer after the age of

50.
Most people diagnosed with stomach cancer are in their late
Aging 60s, 70s, and 80s.

It is most common in Asian/Pacific Islanders.
Ethnicity
An increased risk of stomach cancer is seen with diets

containing large amounts of smoked foods, salted fish
and meat, and pickled vegetables.
Nitrates and nitrites are substances commonly found in
cured meats. They can be converted by certain
Diet bacteria, such as H. pylori, into compounds that have
been found to cause stomach cancer in animals.
On the other hand, eating fresh fruits and vegetables
that contain antioxidant vitamins (such as A and C)
appears to lower the risk of stomach cancer.

Smoking increases stomach cancer
risk, particularly for cancers of the
upper portion of the stomach closest
to the oesophagus.
Tobacco use The rate of stomach cancer is about
doubled in smokers.
Being very overweight or obese has

emerged as a possible cause of
cancers of the cardia (the part of the
stomach nearest the oesophagus),
Obesity but the strength of this link is not
yet clear.

This may be because it allows more nitrite-producing
bacteria to be present. Also, acid production goes down
after ulcer surgery, and there may be reflux (backup) of
Previous bile from the small intestine into the stomach.
stomach The risk continues to increase for as long as 15 to 20
surgery
years after surgery.
Certain cells in the stomach lining normally make

intrinsic factor (IF), which is a substance needed to
absorb vitamin B12 from foods.
Pernicious People without enough IF may end up with a vitamin
anaemia B12 deficiency, which affects the body's ability to make
new red blood cells.
a condition in which excess growth of the stomach lining

leads to the formation of large folds in the lining and to
low levels of stomach acid.
Menetrier Because this disease is very rare, the exact increase in the
disease risk of stomach cancer is not known.

Hereditary diffuse gastric cancer is an inherited
condition that greatly increases the risk of developing
stomach cancer.
This condition is quite rare, but the lifetime stomach
Inherited cancer
cancer risk among affected people is about 70% to
syndromes 80%.
Researchers recently discovered the gene (E-
cadherin/CDH1) responsible for this condition.
Hereditary non-polyposis colorectal cancer (HNPCC,

also known as Lynch syndrome) and familial
adenomatous polyposis (FAP) are also inherited
genetic disorders. They cause a greatly increased risk
of getting colorectal cancer and a slightly increased
risk of getting stomach cancer in family members who
Inherited cancer have these gene mutations.
syndromes People who carry mutations of the inherited breast
cancer genes BRCA1 and BRCA2 may also have a
higher rate of stomach cancer.

For unknown reasons, individuals with Type A blood have
an increased risk of developing gastric cancer.
Type A blood
People with several first-degree relatives who have had

stomach cancer are more likely to develop this disease
Family history of
gastric cancer
Epstein-Barr virus has also been found in the stomach

cancers of about 5% to 10% of people with this disease.
These people tend to have a slower growing, less
Epstein-Barr aggressive cancer with a lower tendency to spread.
infection

Benign Gastric conditions
Gastric polyps
Especially the Adenomatous type
Gastric Ulcer not with duodenal ulcer

Clinical Presentation
1. History
Asymptomatic - superficial & surgically curable
Weight loss & Persistent abdominal pain
Anorexia
Nausea, Abdominal pain & early satiety
Due to tumor mass
Palpable abdominal mass long-standing growth,
regional extension

Dysphagia
Melena ,or Haematemesis
In <20% of patients
Pseudoachalasia Syndrome
Involvement of Auerbachs plexus or
Due to malignant Obstruction at G-E junction

Clinical Presentation(Cont)
2. Physical Signs
Most Signs indicate an advanced disease
intraabdominal lymph nodes
supraclavicular lymph nodes (virchows node)

Ovary (Krukenbergs tumor)
Periumbilical lyph node (Sister Mary Joseph node)
Peritoneal cul-de-sac (Blumers shelf): palpable on

rectal or vaginal examination

Malignant ascites
Liver most common site for hematogenous

spread of tumor
Feculent Emesis: Gastro colic fistula

GOO (Gastric Outlet Obstruction)
Small bowel obstruction

Pleural effusions
Unusual clinical features (Para-neoplastic
manifestations)
Migratory thromboplebitis,
Microangiopathic hemolytic anemia &
Acanthosis nigrans
Hypercoagulable state

Work Up (DIAGNOSIS)
1. Lab Studies
CBC: To R/O Anemia
Electrolytes & LFT
Serologic markers
Carcino-embryonic Ag (CEA)
Increased in 45-50% of cases
Cancer Antigen (CA19-9)
Increased in 20% of the cases

2.Double contrast radiographic examination
Simplest procedure epigastric complaints
Helps detect small lesions by improving
mucosal detail
Stomach should be distended decreased
distensibility may be the only indication of
diffused infiltrative carcinoma

Work Up(Cont)
3. Upper GI-Endoscopy
More sensitive & specific
Tissue Dx & Anatomical localization
50% of malignant ulcers appear benign grossly
Single Bx: 70% sensitivity
Brush cytology may increase sensitivity
7 biopsies: From ulcer margin & base
Increases sensitivity to 98%
Diagnosing Linitis plastica may be difficult
Mucosal Biopsy may be falsely negative b/c
submucosa is affected

Work Up(Cont)
4. Endoscopic U/S
Precise in staging &
assessing depth of
invasion or involvement
of adjacent structures

5. Barium Studies
Can identify both malignant ulcers &
infiltrative lesions
As high as 50% false negativity in early
cases
75% accuracy
In LINITIS PLASTICA
Barium meal may be superior than
Endoscopy
Decreased distensibility , stiff, Leather-
Flask appearing stomach

Work Up(Cont)
6. Abdomino-pelvic Ultrasound or CT- scan
Done after settling the Diagnosis
Secondaries <5mm may be missed
Sensitivity limited if L.N. size is<8mm
Only 50-70% accuracy in assessing T-stage of
the Disease
False positive if inflammatory LAP present
7. PET
Using 18-flurodeoxy glucose
More sensitive than CT in detecting distant
spread
May be False negative if tumor cells have low
metabolic activity
Work Up(Cont)
8. CXR
To R/O metastatic lesions
9. Staging Laparascopy
More sensitive than CT & EUS
Can directly see Liver surface,
peritoneum& Local L.Ns.
Indicated in all medically fit individuals
10. Histo-pathology
Tells us the histological sub-type

Gross Morphology & Histologic Sub-types
1. Gross appearance of pathology specimens
A. Ulcerative
B. Polypoid
C. Schirrhous(Diffuse Linitis Plastica)
D. Superficial Spreading
E. Multicentric
F. Barrett Ectopic Adenocarcinoma

2. Histologic Sub-types
1. Adenocarcinomas (Tubular , Papillary ,
Mucinous , Signet-ring or Undeferentiated)
2. Lymphomas
3. Stromal Tumors
4. Carcinoid tumors
5. Adenoacanthomas and
6. SCC

Patterns Of Spread
1.Direct extension
Omentum
Pancreas
Diaphragm
Transverse Colon , Meso- Colon
2. Lymphatic spread
3. Hematogenous spread
4. Transperitoneal spread

Staging
Staging Systems
2Major Classifications
1. Japanese Classification (Based on L.N stations)
2. TNM staging
T-Stage: Dependent on depth of invasion
,not size
N-Stage: Based on # of positive L.Ns
rather than proximity of L.Ns to the
primary tumor
TNM-Staging

Staging system for gastric ca
Stage TNM Features No. of Cases % 5 year survival,
%
0 TisN0M0 Node negative; 1 90

Limited to mucosa
IA T1N0M0 Node negative; 7 59
Invasion of lamina propria or
submucosa
IB T2N0M0 Node negative; 10 44
Invasion of muscularis
propria
II T1N2M0 Node positive; invasion 17 29
T2N1M0 beyond mucosa but within
wall
T3N0M0 Node negative, extension
through wall
IIIA T2N2M0 Node positive; invasion of 21 15
T3N1-2M0 muscularis propria or
through wall
IIIB T4N0-1M0 Node negative; adherence to 14 9
surrounding tissue
IV T4N2M0 Node positive; adherence to 30 3
surrounding tissue
T1-4N0-2M1 Distant metastases
TREATMENT

SURGICAL TREATMENT
Complete surgical removal of the tumor with
resection of adjacent lymph nodes
Only chance for cure
Provides the best palliation
Provides the most accurate staging
Possible in <1/3 of patients

SURGICAL TREATMENT cont.
Subtotal gastrectomy distal carcinomas
Total or near-total gastrectomies more

proximal tumors
???Extended lymph node dissection

Operative Mx
1st Successful Gastric resection: In 1881 by Billroth
Patient died 14mos latter
Extent of Gastric resection
Total Gastrectomy Vs Ro (Complete removal of
primary tumor with negative surgical margins)

Operative Mx(Cont)
Extent of Gastric resection
Is site Dependent
Focuses on complete removal of the gastric Ca
4-5cm margin from the gross edge of the
tumor

Operative Mx(Cont)
Total Gastrectomy
Increased Mortality & Morbidity
Does not have survival benefit
Proximal Resections
Appear to have similar perioperative
Morbidity/Mortality to total gastrectomy
Extended Organ Resection

Reserved for Node negative T4 lesions
Invaded portions of the Diaphragm ,Pancreas , Spleen
, Adrenal gland or Colon
Operative Mx(Cont)
Endoscopic Sub-mucosal Resection

May be justified for mucosal cancers
3% will be expected to have positive L.Ns
Sub-mucosal Cancer
20% nodal positivity
Consider limited Laparascopic resections OR
limited open operations

Distal Sub-total Gastrectomy
11/01/2012G.C Billroth II Aregawi Kassa-Mx of Gastric Ca 44

Distal Sub-total Gastrectomy
Billroth I Roux-en- Y
Total gastrectomy with roux-in-Y anastomosis

Operative Techniques(Cont)
3. Proximal Gastrectomy
For proximal Adeno-Carcinoma
Alkaline reflux may be a problem
Many still prefer total gastrectomy for
proximal lesions

3.Proximal Gastrectomy

Operative Techniques(Cont)
Extent of L.N. Dissection
The extent of L.N. involvement can be
predicted by the site of the primary lesion
Extent of Node dissection can then be
standardized
At least 15 L.Ns should be sampled
With15 L.Ns sampled , accurate N-staging can
be obtained

D1 Lymphadenectomy: Dissection of Perigastric L.Ns
D2 Lymphadenectomy: Dissection of Hepatic , Lt Gastric

, Celiac & Splenic a.as as well as those in splenic
hilum(Extended lymphadenectomy
D3 Lymphadenectomy: D2+ Dissection of L.Ns in the

portahepatis & Peri Aortic L.Ns(Super extended
lymphadenectomy)

Extent of L.N. Dissection
D1 Lymphadenectomy
D2 and D3 Lymphadenectomy
11/01/2012G.CAregawi Kassa-Mx of Gastric Ca 52
Adjuvant & Neo-adjuvant Rx Of Gastric Cancer
80% of patients experience a local recurrence

at some time in their illness
Neo-adjuvant Chemo Rx
Administered as a means of Down
Staging a locally advanced tumor

Local Palliation For Advanced Gastric Ca
Majority of patients require palliation at some point in
the course of the illness
Palliative Rx for advanced Disease can be either LOCAL

or SYSTEMIC
Cytotoxic Chemo Rx: Most effective for metastatic Ds,

inadequate for local Symptoms

Local Palliation For Advanced Gastric Ca
(Cont)
Locally advanced OR Locally recurrent Diseases
requires multidicipilinary MX
Endoscopic
Surgical
RT or Other approaches
Palliative resection(Gastrectomy)
May provide symptomatic relief
Pain
Bleeding
Obstruction
Perforation
Non-Surgical Palliation
A. Endoscopic stent placement : For obstructive

Symptoms
B. Radiation Rx : To control pain , bleeding , or

obstruction
C. Endoscopic Laser Rx : To palliate dysphagia due to

obstruction
Laser Photocoagulation: large tumors with diffuse
bleeding

5Year survival rates
Stage0 : >90%
Stage Ia: 60-80%
StageIb: 50-60%
Stage II: 30-40%
Stage IIIA: 20%
Stage IIIb: 10%
Stage IV: <5%

Gastric Lymphoma
Acount for 4% of gastric malignancies
Stomach is the commonest site of primary GI Lymphoma
>95% are NHL and Most are B-cell types
Thought to arise in MALT

In the setting of chronic Gastritis stomach acquires
MALT which can undergo malignant transformation
H-Pylori thought to be the culprit

Low grade MALT Lymphoma
May undergo degeneration to high grade Lymphoma
When H-Pylori is eradicated , Gastritis improves , Low
grade MALT often disappears
High grade Gastric Lymphoma: requires

aggressive oncologic treatment

Gastric Lymphoma(Cont)
Similar symptoms as Gastric Ca patients

Systemic Symptoms: Fever , Weight loss and Night
sweat: Occur in about 50% of patients
Tumor may bleed or obstruct

LAP/Organomegally : suggest systemic disease
Dignosis is based on Endoscopy & Biopsy

Much of the tumor may be submucosal

Radical subtotal Gastrectomy
For tumor limited to stomach & regional L.Ns
Primary Chemo therapy without operation
Good results
Perforation & bleeding is a recognized complication

Malignant Gastrointestinal Stromal Tumor
Acount 1% gastric malignancy
Arise in the mesenchymal tissue
From a multi-potential cell line of origin
Varying patterns of differentiation
Smooth muscle type
Epitheloid type

Malignant Gastrointestinal Stromal
Tumor(Cont)
2/3rd of all gut malignant GISTs occur in stomach
Epithelial cell stromal GIST
Most common cell type arising in the stomach
Cellular spindle type
Next most common

Tumor(Cont)
They are submucosal tumors, slow growing
Smaller lesions found incidentally
Symptoms may ulcerate & cause bleeding
Larger lesions produce symptoms

Weight loss
Abdominal pain
Fullness
Early satiety & bleeding
Tumor(Cont)
Abdominal mass may be palpated
Spread is Hematogenous , rarely lymphatic

To liver &/or lung
Diagnosis is by Endoscopy & Biopsy , EUS (Endoscopic

ultrasound) , CT-scan

Tumor(Cont)
Most GIST occur in the body of the stomach
Can also occur in the Fundus or Antrum
Almost always solitary
Wedge resection with adequate margin is adequate

Prognosis depends on tumor size &Mitotic count
Invasion of adjacent structures is evidence of malignancy

If safe ,En-block resection of involved surrounding
organs

Tumor(Cont)
Most patients with low grade lesions are cured
80% 5Yr survival
30% 5Yr survival for high grade lesions
GISTs are usually positive for the proto-oncogen C-Kit
IMATINIB (Gleevec)
Blocks the activity of the tyrosine kinase product of C-
kit
Shows promising activity in patients with metastatic
or unresectable GIST

Gastric Carcinoid Tumors
They are unusual in stomach compared to mid-gut &
hindgut locations
Gastric Carcinoids
Comprise 3% of GI Carcinoids
Clearly have malignant potential
Patients with Atrophic Gastritis or Pernicious Anemia
are at an increased risk
Tumors are submucosal , may be quite small

Biopsy may be difficult
EUS: To define size &depth of the lesion

They should be resected
Endoscopic removal: If confined to mucosa
Survival is excellent for node negative pts(>90% 5Yr

survival)
Node positive patients: have 50% survival

Summary
Gastric Ca remains to be one of the most common form
& the 2nd most common killer of all malignancies
Most patients present late

H-Pylori infection plays a key role
Preoperative assessment of the extent of the disease is

important
Surgery is the only curative Rx option
Screening & early detection may have a role in high risk

communities

Thank u

Gastric CA by Dr. Aregawi Kassa

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Management Of Gastric Cancer

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 1

Most common & lethal cancer

Significant geographical , ethnic & socio-

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 2

Decrease incidence and mortality rates for gastric

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 3

According to Laurens classification

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 4

For Intestinal type

Dysplasia (Low or High grades)

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 6

Stomach cancer is more common in men than in women.

There is a sharp increase in stomach cancer after the age of

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 7

An increased risk of stomach cancer is seen with diets

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 8

Being very overweight or obese has

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 9

Certain cells in the stomach lining normally make

a condition in which excess growth of the stomach lining

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 10

Hereditary non-polyposis colorectal cancer (HNPCC,

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 11

People with several first-degree relatives who have had

Epstein-Barr virus has also been found in the stomach

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 12

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 13

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 14

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 15

supraclavicular lymph nodes (virchows node)

Periumbilical lyph node (Sister Mary Joseph node)

Peritoneal cul-de-sac (Blumers shelf): palpable on

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 16

Liver most common site for hematogenous

Feculent Emesis: Gastro colic fistula

Small bowel obstruction

Microangiopathic hemolytic anemia &

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 18

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 19

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 20

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 21

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0 TisN0M0 Node negative; 1 90

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 37

Possible in <1/3 of patients

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 38

Subtotal gastrectomy distal carcinomas

Total or near-total gastrectomies more

???Extended lymph node dissection

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 39

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 40

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 41

Extended Organ Resection

Endoscopic Sub-mucosal Resection

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 43

11/01/2012G.C Billroth II Aregawi Kassa-Mx of Gastric Ca 44

11/01/2012G.C Aregawi Kassa-Mx of Gastric Ca 46