Metastatic Adenocarcinoma of Stomach

• Adenocarcinoma of the Stomach

• Definition

• Malignant gland forming neoplasm of the stomach, exclusive of the EGJ and gastric cardia

Gastric Cancer

Epidemiology

Forth common types of cancer

Second most common cancer related death

Geographic variations (ten times)

Continuing decline

Primarily a decline of distal GC

(2000) (2000)

Geographic variations

Gastric Cancer

Environmental factors

H. pylori Genetic factors

Etiological Factors of Gastric Cancer

Precancerous changes

The role of H. Pylori infection in gastric carcinogensis

Type I carcinogen1994 by IARC

Gastric Cancer

Attributable risk50%~73%

Epidemiological studie

Environmental factors

Environmental factors are involved

Japanese immigrants in US: 25%

Second generation: >50%

Subsequent generations: comparable to General US population

Environmental factors

Lower socioeconomic status

Tobacco/alcohol

Fresh vegetable/fruits/Micronutrition

Poor food storage

Eating salted/Smoked food

Mucosal damage

Pro-carcinogen/Carcinogen

Lack of antioxidant

GASTRIC CANCERC

Genetic factors

• The majority of gastric tumor are sporadic in nature

• There are rare inherited gastric cancer predisposition.

Precancerous changes

Precancerous lesions

Precancerous conditions

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

Nature history of gastric dysplasia

No

Dysplasia

No

DysplasiaMild

Dysplasia

Mild

Dysplasia

Moderate

Dysplasia

Moderate

Dysplasia

High-grade

Dysplasia

High-grade

Dysplasia

Gastric

adenocarcinoma

Gastric

adenocarcinoma

5 years5 years 5 years5 years

5 years5 years

3 months-2 years3 months-2 years

10%10%

10%10%

50%-90%50%-90%

60%60%60%60%

10%10%

Precancerous condition

• Defined as those clinical setting with higher risk of

developing gastric cancer

Chronic atrophic gastritis

Gastrectomy

Pernicious anemia

Menetrier’s disease

Chronic gastric ulcer

Gastric polyps

Postulated sequence of histologic events in the progression to gastric adenocarcinoma and potential contributory factors

H. PyloriH. Pylori Other factorsOther factors

Chronic Superficial Gastritis

Chronic Superficial Gastritis

Intestinal Metaplasia

Intestinal Metaplasia

Atrophic Gastritis

Atrophic Gastritis DysplasiaDysplasia

FAP or Adenomas

FAP or Adenomas

Gastric Adenocarcinoma

Gastric Adenocarcinoma

Other factorsOther factors

AssociationAssociation Strong Association

Strong Association

Pathology

Stages

Morphology

Pathohistologic classification

Metastasis

Stages

• Early stage limited in the mucosa and sub mucosa layers, no matter with or without lymph node metastasis Classified by the Japanese Society for Gastric Cancer <1cm <0.5cm

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

TNM classification (UICC)

0 Tis N0 M0 III A T2 N2 M0

I A T1 N0 M0 T3 N1 M0

I B T1 N1 M0 T4 N0 M0

T2 N0 M0 III B T3 N2 M0

II T1 N2 M0 IV T4 N2 M0

T2 N1 M0 T1~3 N3 M0

T3 N0 M0 any T any N M1

Morphology---Early stage

Morphology---Early stage

Morphology---Early stage

Morphology ---Advanced stage

Histopathological classification

Histology

Adenocarcinoma 90%

Lymphoma 5%

Stromal 2%

Carcinoid <1%

Metastasis <1%

Adenosquamous/squamous <1%

Miscellaneous <1%

Origin (Lauren)

• Intestinal type

associated with most environmental risk factors

carries a better prognosis

shows no familial history

• Diffuse type

consists of scattered cell clusters with poor prognosis

Growth pattern (Ming)

• Expanding type

grew en mass and by expansion

resulting in the formation of discrete tumor nodules

with relatively good prognosis

• Infiltrative type

invaded individually

with poor prognosis

Metastasis

Direct invasion

Lymph node dissemination

Blood spread

Intraperitoneal colonization

Special term

• Blumer shelf

A shelf palpable by rectal 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

Clinical manifestationSigns and Symptoms

Early Gastric Cancer

Asymptomatic or silent 80%

Peptic ulcer symptoms 10%

Nausea or vomiting 8%

Anorexia 8%

Early satiety 5%

Abdominal pain 2%

Gastrointestinal blood loss <2%

Weight loss <2%

Dysphagia <1%

Signs and Symptoms

Advanced Gastric Cancer

Weight loss 60%

Abdominal pain 50%

Nausea or vomiting 30%

Anorexia 30%

Dysphagia 25%

Gastrointestinal blood loss 20%

Early satiety 20%

Peptic ulcer symptoms 20%

Abdominal mass or fullness 5%

Asymptomatic or silent <5%

Duration of symptoms

Less than 3 month 40%

3-12 months 40%

Longer than 12 month 20%

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

Sister Mary Joseph’s node

Laboratory tests

Iron deficiency anemia

Fecal occult blood test (FOBT)

Tumor markers (CEA, Ca19-9)

Diagnosis

Endoscopic diagnosis

--- biopsy needed for definitive diagnosis

Radiologic diagnosis

Detection of early gastric cancer

Endoscopic diagnosis

• In patients with signs and symptoms suggestive of

GC, and/or with compatible risk factors or paraneoplastic

conditions, 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

Endoscopic features of gastric cancer

Radiologic diagnosis • For reasons of cost and availability, radiography may sometimes be the first diagnostic procedure performed

• Classic radiography signs of malignant gastric ulcer

asymmetric/distorted ulcer crater

ulcer on the irregular mass

irregular/distorted mucosal folds

adjacent mucosa with obliterated /distorted area gastric

nodularity, mass effect, or loss of dispensability

Radiologic diagnosis

Distal GC Proximal GC Linitis plastica

Detection of early gastric cancer

• Endoscopic screening

general population or high risk persons

• Careful observation

Differential diagnosis

Gastric Cancer

Gastric Ulcer

Complications

• GI bleeding 5%

• Pylorus/cardia obstruction

• Perforation ulcer type

Treatment

Surgical resection

EMR

Adjuvant therapy

Palliative therapy

Endoscopic mucosal resection

Gastric cancer lesion confined to mucosa layer

Endoscopic ultrasound (EUS) is helpful in stageing GC

Endoscopic mucosal resection

Endoscopic mucosal resection

Chemotherapy Regimen Approximate Survival

Response rate BenefitFluorouracil +doxorubicin 30% No

+ mitomycin (FAM)

Fluorouracil + doxorubicin 30% No

Semustine (FAMe)

Fluorouracil + doxorubicin 30% No

+ cisplatin (FAP)

Etoposide + doxorubicin 40% No

+ cisplatin (EAP)

Etoposide + leucovorin 30% No

+ fluorouracil (ELF)

Fluorouracil +doxorubicin 40% Unconfirmed

+ methotrexate (FAMTX)

AIM OF COMBINATION THERAPYAIM OF COMBINATION THERAPY

INCREASED EFFICACYINCREASED EFFICACY

Different mechanisms of action Compatible side effects

Different mechanisms of resistance

ACTIVITYACTIVITY SAFETYSAFETY

Side effects of chemotherapySide effects of chemotherapy

Mucositis

Nausea/vomiting

Diarrhea

Cystitis

Sterility

Myalgia

Neuropathy

Alopecia

Pulmonary fibrosis

Cardiotoxicity

Local reaction

Renal failure

Myelosuppression

Phlebitis

Metal stent

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

Prevention

• Eradication of H. Pylori infection 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

Prevention

• Tightly follow up those with precancerous condition

• Endoscopic or radiologic screening