Gastric cancer

By: NURUL AIN ALAN HAFIFI

GROUP 915TH COURSE

2012

Anatomy

Physiology Cell Type Distinctive Ultrastructural

FeaturesMajor Functions

Surface-foveolar mucous cells

Apical stippled granules up to 1  m in diameter

Production of neutral glycoprotein and bicarbonate to form a gel on the gastric luminal surface; neutralization of hydrochloric acida;

Mucous neck cell Heterogeneous granules 1–2  m in diameter dispersed throughout the cytoplasm

Progenitor cell for all other gastric epithelial cells; glycoprotein production; production of pepsinogens I and II

Parietal cell Surface membrane invaginations (canaliculi); tubulovesicle structures; numerous mitochondria;

Production of hydrochloric acid production of intrinsic factor production of bicarbonate

Chief cell Moderately dense apical granules up to 2  m in diameter; prominent supranuclear Golgi apparatus; extensive basolateral granular endoplasmic reticulum

Production of pepsinogens I and II, and of lipase

Cardiopyloric mucous cell

Mixture of granules like those in mucous neck and chief cells; extensive basolateral granular endoplasmic reticulum

Production of glycoprotein Production of pepsinogen II

 

Gastric cancer O GC is one of the most frequent malignant diseases (2 place in

structure of malignant diseases)O The rate of morbidity decreases during last decades (first of

all in economically developed countries) – BUT!O Annually in the world 1 million new cases of GC are

registered O The rate of morbidity widely varies depending on region (the

greatest disease is noted at men of Japan - 114 on 100.000, the least among white women of the USA -less than 5 on 100.000)

O The majority of developing countries concern to be the countries with a high rate of morbidity (50 and more on 100 thousands)

O The men’s morbidity in 1,5-2 times larger than women’s O The rate of morbidity increases after 50 years, and reaches a

maximum in 60-70 years

Gastric Cancer

Epidemiology

One of the most common types of cancer

Second most common cancer related death

Geographic variations (ten times)

Continuing decline

(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

Helicobacter Pylori

infection

Epidemiological studies

Also associated with risk of MALT

lymphomaPrimary cause ofGastric Cancer

Higher rik to get Gastric adenocarcinoma

Environmental factors

Lower socioeconomic status

Tobacco/alcohol

Low intake of Fresh vegetable/fruits/Micronutrition

Poor food storage

Eating salted/Smoked food

Mucosal damage

Pro-carcinogen/Carcinogen

Lack of antioxidant

GC

Genetic factors

• The majority of gastric tumor are sporadic in nature

• There are rare inherited gastric cancer predisposition traits such as germline p53 (Li-Fraumeni syndrome) E-cadherin (CDH1) alterations in diffuse gastric cancers

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 to gastric adenocarcinoma• 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 (diseases) 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

Correa hypothesis

Type of GCHistologically

a. Adenocarcinoma

b. Leiomyosarcoma

c. Lymphomas

d. Carcinoid Tumours

The macroscopic forms of gastric cancers are classified by (Bormann classification) into:-

1. Polypoid or Proliferative

2. Ulcerating

3. Ulcerating/Infiltrating

4. Diffuse Infiltrating (Linnitus-

Plastica)

v

Japanese classification

STAGING OF GASTRIC CANCER:

a. TNM System

b. CT Staging

c. PHNS Staging System (Japanese)

P-factor (Peritoneal dissemination)

H-factor (The presence of hepatic metastases)

N-factor (Lymphnodes involvement)

S-factor (Serosal invasion)

TNM classification (UICC)

Stages

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

• Advanced stage invaded over submucosa According to Bormann’ classification

Morphology---early stage

Morphology---early stage

Morphology---early stage

Morphology ---advanced stage

Pathohistologic classification

HistologyAdenocarcinoma 90%Lymphoma Leiomyoma Carcinoid

Metastasis

Direct invasion

Lymph node dissemination

Blood spread

Intraperitoneal colonization

Gastric lymph nodes

Lymph node station number

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

EVALUATION OF GASTRIC CANCER:

History Clinical manifestation

Investigations

Clinical manifestation

Signs and SymptomsEarly Gastric CancerAsymptomatic 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 CancerWeight 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)

• Sister Mary Joseph’s node: umbilical

lymphadenopathy

Linitis plastica

Sister Mary Joseph’s node

Investigation O A. Upper gastero intestinal endoscopy with

multiple biopsy and brush cytology

O B. Radiology:O CT Scan of the chest and abdomenO US upper abdomen O Barium meal

O C. Diagnostic laparoscopy

Endoscopic features of gastric cancer

Radiologic diagnosis

Distal GC Proximal GC Linitis plastica

Detection of early gastric cancer

• Endoscopic screening general population or high risk persons

• Careful observation

• Japan is the only country that had conducted large nationwide mass population screening of asymptomatic individuals for gastric malignancy

Complications

•Malnutrition•Malabsorption •Bowel obstruction •Gastrointestinal bleeding • Pylorus/cardia obstruction• Perforation ulcer type

Treatment of GC

OSurgical OChemotherapyORadiotherapy

Surgery (Early or Advanced Cancer)

O Endoscopic mucosal resection EMRO Subtotal (partial) gastrectomy: This approach is

often used if the cancer is in the lower part of the stomach close to the intestines. Only part of the stomach is removed, sometimes along with part of the esophagus or the first part of the small intestine. Nearby lymph nodes are also removed

O Total gastrectomy: This method is used if the cancer has spread throughout the stomach. It is also often used if the cancer is in the upper part of the stomach. The surgeon removes all of the stomach.

Endoscopic mucosal resection(EMR)

Gastric cancer lesion confined to mucosa layer

Endoscopic ultrasound (EUS) is helpful in stageing GC

Endoscopic mucosal resection (EMR)

Endoscopic mucosal resection (EMR)

Subtotal gastrectomy

Total gastrectomy

Chemotherapy

• Adjuvant chemotherapy may increase 5 years survival rates and decrease the relapse rates

• Combination chemotherapy are recommended

Principles of Combination Chemotherapy

• Only those agents proven effective should be used• Each agent used should have a different mechanism of action• Each drug should have a different spectrum of toxicity• Each drug should be used at maximum dose• Agents with similar dose-limiting toxicities can be combined safely only by reducing doses, resulting in decreased effects

Chemotherapy Regimen Approximate Survival Response rate BenefitFluorouracil +doxorubicin 30% No+ mitomycin (FAM)Fluorouracil + doxorubicin 30% NoSemustine (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)

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

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 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