Gastric cancer

By: NURUL AIN ALAN HAFIFI GROUP 91 5TH COURSE 2012

Anatomy

Physiology
Cell Type Distinctive Ultrastructural Features Apical stippled granules up to 1 m in diameter Major Functions Production of neutral glycoprotein and bicarbonate to form a gel on the gastric luminal surface; neutralization of hydrochloric acida; Progenitor cell for all other gastric epithelial cells; glycoprotein production; production of pepsinogens I and II Production of hydrochloric acid production of intrinsic factor production of bicarbonate Production of pepsinogens I and II, and of lipase

Surface-foveolar mucous cells Mucous neck cell

Heterogeneous granules 12 m in diameter dispersed throughout the cytoplasm Surface membrane invaginations (canaliculi); tubulovesicle structures; numerous mitochondria; Moderately dense apical granules up to 2 m in diameter; prominent supranuclear Golgi apparatus; extensive basolateral granular endoplasmic reticulum

Parietal cell
Chief cell

Cardiopyloric mucous cell

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

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

O O O

structure of malignant diseases) The rate of morbidity decreases during last decades (first of all in economically developed countries) BUT! Annually in the world 1 million new cases of GC are registered 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) The majority of developing countries concern to be the countries with a high rate of morbidity (50 and more on 100 thousands) The mens morbidity in 1,5-2 times larger than womens The rate of morbidity increases after 50 years, and reaches a maximum in 60-70 years

Epidemiology
One of the most common types of cancer
(2000)

Second most common cancer related death

(2000)

Gastric Cancer

Continuing decline

Geographic variations (ten times)

Geographic variations

Etiological Factors of Gastric Cancer

H. pylori

Genetic factors

Gastric Cancer

Environmental factors

Precancerous changes

The role of H. Pylori infection in gastric carcinogensis

Epidemiological studies
Higher rik to get Gastric adenocarcinoma

Helicobacter Pylori infection

Primary cause of Gastric Cancer

Also associated with risk of MALT lymphoma

Environmental factors
Lower socioeconomic status
Mucosal damage

Poor food storage Low intake of Fresh vegetable/fruits /Micronutrition

Tobacco/alcohol Pro-carcinogen/ Carcinogen

GC

Lack of antioxidant Eating salted/ Smoked food

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

5 years No Dysplasia 60% Mild Dysplasia 60% 5 years 10% Moderate Dysplasia 5 years 3 months-2 years Gastric adenocarcinoma 50%-90% 10% 10% High-grade Dysplasia

Precancerous condition
Defined as those clinical setting (diseases) with

higher risk of developing gastric cancer

Chronic atrophic gastritis Gastrectomy Pernicious anemia Menetriers disease Chronic gastric ulcer Gastric polyps

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

Correa hypothesis
H. Pylori Other factors FAP or Adenomas Other factors

Chronic Superficial Gastritis

Intestinal Metaplasia

Gastric Adenocarcinoma

Atrophic Gastritis

Dysplasia

Association

Strong Association

Type of GC
Histologically

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 (LinnitusPlastica)

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
Histology Adenocarcinoma Lymphoma Leiomyoma Carcinoid 90%

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 Symptoms
Early Gastric Cancer Asymptomatic or silent Peptic ulcer symptoms Nausea or vomiting Anorexia Early satiety Abdominal pain Gastrointestinal blood loss Weight loss
Dysphagia 80% 10% 8% 8% 5% 2% <2% <2%

<1%

Signs and Symptoms

Advanced Gastric Cancer Weight loss Abdominal pain Nausea or vomiting Anorexia Dysphagia Gastrointestinal blood loss Early satiety Peptic ulcer symptoms Abdominal mass or fullness Asymptomatic or silent 60% Duration of symptoms 50% Less than 3 month 40% 30% 3-12 months 40% 30% Longer than 12 month 20% 25% 20% 20% 20% 5% <5%

Special signs & terms

Linitis plastica: diffusely infiltrating with a rigid stomach Virchows node: supraclavicular lymphadenopathy (left)

Sister Mary Josephs node: umbilical

lymphadenopathy

Linitis plastica

Sister Mary Josephs node

Investigation
O A. Upper gastero intestinal endoscopy

with multiple biopsy and brush cytology

O B. Radiology:

O
O O

CT Scan of the chest and abdomen US upper abdomen 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
O Surgical O Chemotherapy O Radiotherapy

Surgery (Early or Advanced Cancer)

O Endoscopic mucosal resection EMR O 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 Response rate
30% 30%

Survival
No No

Benefit
Fluorouracil +doxorubicin + mitomycin (FAM) Fluorouracil + doxorubicin Semustine (FAMe) Fluorouracil + doxorubicin + cisplatin (FAP) Etoposide + doxorubicin + cisplatin (EAP) Etoposide + leucovorin + fluorouracil (ELF) Fluorouracil +doxorubicin Unconfirmed + methotrexate (FAMTX)

30%
40% 30% 40%

No
No No

Side effects of chemotherapy

Mucositis

Alopecia

Pulmonary fibrosis Nausea/vomiting

Cardiotoxicity
Local reaction Renal failure

Diarrhea
Cystitis Sterility Myalgia

Myelosuppression
Phlebitis

Neuropathy

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