Gastric cancer 胃癌

(Gastric adenocarcinoma)
Department of Gastroenterology
Sir Run Run Shaw Hospital

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 Gastric cancer
• Epidemiology
• Etiology and Pathogenesis
– Genetics
– Precancerous changes
• Clinic features
• Diagnosis
– Pathology
• Treatment
• Preventions
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Epidemiology

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 Etiological Factors of Gastric Cancer

H. pylori Genetic factors

Gastric
Cancer

Environmental Precancerous
factors changes
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 H. Pylori infection

Epidemiological
studies
RF: 2.8~6 folds

Type I carcinogen
1994 by IARC
Attributable risk
50%~73%
Animal modes
(Mongolian gerbil)
Gastric Cancer
Honda et al . 1998
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Watanabe et al. 1998
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 Environmental factors
Lower socioeconomic
status
Mucosal damage
Poor food storage

Pro-carcinogen/
Micronutrition
Carcinogen
GC

Tobacco/alcohol
Lack of antioxidant
Eating salted/
Smoked food
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 Dietary factors
• Refrigeration food 9

• Fresh fruits and vegetables

• Fresh fish
• Pickled and salted
• Nitrates
• Red meat/ aflatoxins
 Others
• Cigarette smoking: A carcinogen
• Alcohol
• Obesity
• Inherited predisposition
– Intestinal type: related to environmental causes
– Diffuse type: related to genetic

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 The Correa Pathway
for Intestinal-type Gastric Carcinoma

Intestinal Dysplasia Intramucosal

Antritis
metaplasia LG
H. Pylori
infection
Multifocal Atrophy
HG
(lose glands) Invasive

Journal of Digestive Diseases 2012; 13; 2–9

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 Normal

Foveloar

Isthmis
Neck

Body

Journal of Digestive Diseases 2012; 13; 2–9

Atrophy and intestinal metaplasia
Intestinal metaplasia and high-grade dysplasia

goblet cells

High grade dysplagia

as there are double
layers of nucleus

Journal of Digestive Diseases 2012; 13; 2–9

 Genetic factors

• The majority of gastric tumor are sporadic in nature

• There are rare inherited gastric cancer predisposition traits

such as germline 2-3
p53 (Li-Fraumeni syndrome)
E-cadherin (CDH1) alterations
in diffuse gastric cancers

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Precancerous changes

Precancerous lesions

Precancerous conditions

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 Precancerous lesions
• Defined as those pathological changes predisposed to
gastric cancer
dysplasia

• 10% of patients may progress in severity

• majority of patients either regress or remain stable
• High-grade dysplasia may be only a transient phase in the
progression to gastric cancer
• occurs in atrophic gastritis or intestinal metaplasia
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 Precancerous condition
• Defined as those clinical setting with higher risk of
developing gastric cancer
Chronic atrophic gastritis
Gastrectomy
Pernicious anemia Decrease in red blood cells when the body can’t absorb enough vitamin B12

Menetrier’s disease Excessive mucosal hypertrophy associated with protein loss, associated with gastric neoplasia. Common
in middle-aged men. Also known as Giant hypertrophic gastritis

Chronic gastric ulcer Usually caused by H. Pylori bacteria or non-steroidal anti-inflammatory drugs (NSAIDs)

Gastric polyps Autoimmune gastritis individuals develop gastric polyps. Autoimmune atropgic gastritis (AAG) is a chronic
disease that affects the corpus-fundus of the stomach, and is characterized by the development of two
types of auto-antibodies; anti-parietal cells antibodies and anti-intrinsic factor antibodies.

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Chronic atrophic gastritis

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Atrophy range
 Range of atrophy related with cancer
prevalence
• 对于局限于窦部的轻至中度萎缩患者，没有证据建议
进行监测（证据质量：中； 推荐强度：强）
Menetrier’s disease

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Chronic gastric ulcer

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Gastric polyps

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Clinical manifestation

• Early Gastric Cancer

• Advanced Gastric Cancer

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 Clinical manifestation
Early Gastric Cancer Advanced Gastric
Cancer

Asymptomatic or silent 80% <5%

Peptic ulcer symptoms 10% 20%
Nausea or vomiting 8% 30%
Anorexia 8% 30%
Early satiety 5% 20%
Abdominal pain 2% 50%
Gastrointestinal blood loss <2% 20
Weight loss <2% 60%
Dysphagia <1% 20
Abdominal mass or fullness 0 5% 27
 Complications

• GI bleeding 5%

• Pylorus/cardia obstruction

• Perforation ulcer type

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 Laboratory tests

Iron deficiency anemia

Fecal occult blood test

(FOBT)
Tumor markers (CEA, CA19-9)

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 Diagnosis

Endoscopic diagnosis
--Biopsy needed for definitive diagnosis
--Detection of early gastric cancer
Radiologic diagnosis
Tumor markers

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 Endoscopic diagnosis

• In patients with signs and symptoms suggestive of

GC, and/or with compatible risk factors , the
diagnostic procedure of choice could be
an endoscopic examination
• The diagnostic criteria for early or advanced
gastric cancer under endoscopy are based on the
JRSGC and Bormann’s classification

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 Endoscopic diagnosis
• White-light endoscopy(WLE)
• Chromoendoscopy
• Magnification Endoscopy and Narrow-Band
Imaging （ME-NBI）
• Optimal band imaging system(OBI)
• Endoscopic ultrasonography（EUS）
• Autofluorescence Endoscopy(AFE)
• Confocal laser endomicroscopy（ CLE）
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Chromoendoscopy

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Chromoendoscopy

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ME-NBI

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Optimal band imaging
system(OBI)

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Endoscopic features of GC

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 Differential diagnosis

Gastric Cancer

Gastric Ulcer

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 Radiologic diagnosis

• For reasons of cost and availability, radiography

may sometimes be the first diagnostic procedure

• Classic signs of malignant gastric ulcer

asymmetric/distorted ulcer crater
ulcer on the irregular mass
irregular/distorted mucosal folds
adjacent mucosa with distorted area gastricae
nodularity, mass effect, or loss of distensibility 39
 Radiologic diagnosis

Distal GC Proximal GC Linitis plastica

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 Pathology

Stages
Morphology
Pathohistologic classification
Metastasis

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 Stages
• Early stage
limited in the mucosa and sub-mucosa layers, no matter
with or without lymph node metastasis
Classified by the Japanese Reseach Society for Gastric
Cancer (JRSGC)

• Advanced stage
invaded over sub-mucosa
According to Bormann’ classification
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Stages

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 TNM
• TX, NX or MX indicates 'not assessed'.
T0 - no evidence of primary tumour.
Tis - carcinoma in situ (intraepithelial).
T1 - invades lamina propria or submucosa.
T2 - invades muscularis propria or
subserosa (not visceral peritoneum).
T3 - penetrates visceral peritoneum but not
adjacent structures.
T4 - invades adjacent structures
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 TNM
• N0 - no LN metastasis.
N1 - 1-6 lymph nodes.
N2 - 7-15 lymph nodes.
N3 - more than 15 lymph nodes
• M0 - no distant metastasis.
M1 - distant metastasis, in portal lymph
node, mesenteric, retroperitoneal or more
distant
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Stages

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Morphology---early stage

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Morphology---early stage

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Morphology---early stage

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 Histology

Adenocarcinoma 90%
Lymphoma 5%
Stromal 2%
Carcinoid <1%
Metastasis <1%
Adenosquamous/squamous <1%
Miscellaneous <1%
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 Adenocarcinoma
• Lauren classification Intestinal Type Diffuse Type

– Intestinal type
= Environmental = Familial
= Gastric Atrophy, intestinal = Blood Type A
metaplasia =F>M
=M>F = Younger age group

– Diffuse type
= Increasing incidence with age
= Gland Formation
= Hematogenous Spread
= Exophytic, bulky lesion
= Poorly differentiated
= Transmural, lymphatic spread
= Ulcerating lesion, Frequent
intraperitoneal metastasis

• Location
Inactivation of tumor suppressor genes p53, p16

– Antrum 58% The pyloric antrum is the lower or distal portion above the duodenum. The
opening between the stomach and the small intestine is the pylorus.

– Cardia 20% The entrance to the stomach at the bottom of the esophagus. Main parts of the
stomach include: pylorus antrum, body, fundus and cardia.

– Body 15%
– Whole 7%
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 Adenocarcinoma

Intestinal type Diffuse type 52

 Growth pattern
• Expanding type
grew an mass and by expansion
resulting in the formation of discrete tumor
nodules with relatively good prognosis

• Infiltrative type
invaded individually
with poor prognosis
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 Metastasis

Direct invasion
Lymph node dissemination
Blood spread

Intraperitoneal colonization
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 Special term
• Blumer shelf
A shelf palpable by reactal examination, due to metastatic
tumor cells gravitating from an abdominal cancer and
growing in the rectovesical or rectouterine pouch

• Krukenberg tumor
A tumor in the ovary by the spread of stomach cancer
 Special signs & terms
Linitis plastica: diffusely infiltrating with a
rigid stomach

Virchow’s node: supraclavicular

lymphadenopathy (left)

Irish’s node: axillary lymphadenopathy

Sister Mary Joseph’s node: umbilical

lymphadenopathy 56
 Linitis plastica

• The entire stomach is invaded with cancer, leading

to a leather bottle like appearance 57
Virchow’s node

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 Sister Mary Joseph’s node

a palpable nodule bulging into the umbilicus as a result of

metastasis of a malignant cancer in the pelvis or abdomen.
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 Detection of EGC

• Very important

• Endoscopic screening
general population or high risk persons

• Japan and Korea are the countries that had conducted

large nationwide mass population screening of
symptomatic individuals for gastric malignancy
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 Treatment

EMR/ESD

Surgical resection

Treatment depends to a Adjuvant therapy

large degree on where
the cancer started in the
stomach and how far it Palliative therapy
has spread
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Endoscopic mucosal resection

Gastric cancer
lesion confined
to mucosa layer

Endoscopic ultrasound
(EUS) is helpful in
stageing GC

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EMR

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ESD
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ESD

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取了2块，
病理高分化腺癌
局部腺体欠典型

2017年活检病理：局部腺体欠典型
2019年活检病理：局部腺体不典型
73
50岁女性，胃癌伴转移
58岁女性，体检，萎缩性胃炎
Sample size: 3.4*2.2cm，type: 0-Ⅱb
Tumor size: 约0.5*0.25cm; signet ring cell carcinoma
Invasion depth: LPM
Margin(-)
 •病灶大小
•溃疡有无
differentiated •分化程度
undifferentiated •深度判断
 Surgical resection

• the goal of surgery is to remove all

of the stomach cancer

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 Surgical resection

• Removing a portion of the stomach

(subtotal gastrectomy).
• Removing the entire stomach (total
gastrectomy).
• Removing lymph nodes to look for cancer.
• Surgery to relieve signs and symptoms

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 Chemotherapy

• Adjuvant chemotherapy may increase 5 years

survival rates and decrease the relapse rates

• Combination chemotherapy are recommended

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 Radiation therapy
• be used before surgery (neoadjuvant radiation) to
shrink a stomach tumor so it's more easily
removed.
• be used after surgery (adjuvant radiation) to kill
any cancer cells that might remain around the
stomach.
• often combined with chemotherapy.
• In cases of advanced cancer, radiation therapy
may be used to relieve side effects caused by a
large tumor.
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 Palliative therapy

• Needed for obstruction, pain or

haemorrhage and jaundice

• use of drugs, surgery and radiotherapy

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Metal stent

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 Stage 0

• be treated by surgery . No chemotherapy or

radiation therapy is needed.
• Surgery with either subtotal gastrectomy or
total gastrectomy is often the main
treatment for these cancers. Nearby lymph
nodes are removed as well.
• Some small stage 0 cancers can be treated
by ESD
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 Stage IA

• Removed by total or subtotal gastrectomy.

The nearby lymph nodes are also removed.
•

• ESD maybe an option for some small T1a

cancers.
• No further treatment is usually needed after
surgery.
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Stage IB-1

• The main treatment for this stage of

stomach cancer is surgery (total or subtotal
gastrectomy).

• Chemotherapy (chemo) or chemoradiation

(chemo plus radiation therapy) may be
given before surgery to try to shrink the
cancer and make it easier to remove.
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 Stage IB-2

• either chemoradiation or chemotherapy

alone can been recommend after surgery.

• Another option for patients who were

treated with chemotherapy before surgery is
to give them the same chemo (without
radiation) after surgery.

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 Stage II

• The main treatment is surgery to remove all or

part of the stomach, the omentum, and nearby
lymph nodes.
• Many are treated with chemo or
chemoradiation before surgery to try to shrink
the cancer and make it easier to remove.

• Treatment after surgery may include chemo

alone or chemoradiation. 89
 Stage III

• Surgery is the main treatment . Some patients

may be cured by surgery (along with other
treatments), while for others the surgery may
be able to help control the cancer or help
relieve symptoms.
• Some people may get chemotherapy or
chemoradiation before surgery to try to shrink
the cancer and make it easier to remove. 90
 Stage IV

• Stage IV stomach cancer has spread to distant

organs, a cure is usually not possible.

• But treatment can often help keep the cancer

under control and help relieve symptoms. This
might include surgery, such as a gastric bypass or
even a subtotal gastrectomy in some cases, to
keep the stomach and/or intestines from becoming
obstructed (blocked) or to control bleeding. 91
 Prognosis

• The TNM classification/staging of gastric cancer

is the best prognostic indicator

• The 5 years survival rate depends on the depth of

gastric cancer invasion

• Patients in whom tumors are resectable for cure

also have good prognosis
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 Prevention
• Eradication of H. Pylori infection,especially in
those high risk population
family history of gastric cancer
chronic gastritis with apparent abnormality (atrophy, IM)
post early gastric cancer resection
gastric ulcer

• Management of dietary risk factor

intake adequate amount of fruits, vegetables
minimize their intake of salty/smoked foods
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 Prevention

• Tightly follow up those with precancerous

condition

• Endoscopic or radiologic screening

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Any questions?

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