gastric cancer physio

Gastric Cancer

By: Saeid Afshar

(Ph.D. student of molecular medicine )

November 2014

Hamadan university of medical science

Molecular medicine and genetic department

introduction

• Gastric cancer has been described as

early as 3000 BC in hieroglyphic

inscriptions and papyri manuscripts from

ancient Egypt. The first major statistical

analysis of cancer incidence and mortality

(using data gathered in Verona, Italy from

1760 to 1839) showed that gastric cancer

was the most common and lethal cancer.

http://www.uptodate.com/

INCIDENCE

• Gastric cancer is one of the most common

cancers worldwide

• Gastric cancer used to be the leading

cause of cancer deaths in the world until

the 1980s when it was overtaken by lung

cancer .


INCIDENCE

• The worldwide incidence of gastric cancer

has declined rapidly over the recent few

decades . Part of the decline may be

due to the recognition of certain risk

factors such as H. pylori and other

dietary and environmental risks.


GEOGRAPHICAL VARIATION

• The incidence of gastric cancer varies with

different geographic regions.

• Rates are highest in Eastern Asia, Eastern

Europe, and South America, while the

lowest rates are in North America and

parts of Africa .


• Over 70 percent of gastric cancers occur

in developing countries .

• Gastric cancer is more common in men

than in women, in both developed and

developing countries.

• There are also substantial differences in

incidence among different ethnic groups

within the same region .


GEOGRAPHICAL VARIATION

Geographical Variation in Gastric Cancer Incidence

Parkin DM. International variation. Oncogene 2004; 23: 6329-6340

Pathology

• The risk of gastric cancer is greater among

lower socioeconomic classes. Migrants

from high- to low-incidence nations

maintain their susceptibility to gastric

cancer, while the risk for their offspring

approximates that of the new homeland.

（Dan L. Longo，2012）

• These findings suggest that an

environmental exposure, probably

beginning early in life, is related to the

development of gastric cancer, with dietary

carcinogens considered the most likely

factor(s).


Pathology

• About 85% of stomach cancers are

adenocarcinomas, with 15% due to

lymphomas and gastrointestinal stromal

tumors (GIST) and leiomyosarcomas.

•

gastrointestinal stromal tumors Leiomyosarcoma


Pathology

• Gastric adenocarcinomas may be

subdivided into two categories: a diffuse

type , in which cell cohesion is absent, so

that individual cells infiltrate and thicken

the stomach wall without forming a

discrete mass; and an intestinal type ,

characterized by cohesive neoplastic cells

that form glandlike tubular structures.


Pathology

• Diffuse cancers have defective intercellular

adhesion, mainly as a consequence of loss of

expression of E-cadherin.

• Intestinal-type lesions are frequently

ulcerative, more commonly appear in the

antrum and lesser curvature of the stomach,

and are often preceded by a prolonged

precancerous process, often initiated by

Helicobacter pylori infection.


Pathology

• While the incidence of diffuse carcinomas

is similar in most populations, the intestinal

type tends to predominate in the high-risk

geographic regions and is less likely to be

found in areas where the frequency of

gastric cancer is declining. Thus, different

• etiologic factor(s) are likely involved in

these two subtypes.


Pathology

• In the United States

• , ~30% of gastric cancers originate in the distal stomach,

• ~20% arise in the midportion of the stomach,

• and ~37% originate in the proximal third of the stomach.

• The remaining 13%involve the entire stomach.


Pathology

A: the Endoscopic image of an ulcerating adenocarcinoma. B. Ulcerating

adenocarcinoma, pictorial representation. Picture courtesy: John Hopkins Medicine-

Gastroenterology and Hepatology department. ‘An introduction to Gastric cancer’, 2012.

Etiology

• The long-term ingestion of highconcentrations of nitrates in dried, smoked,and salted foods appears to be associatedwith a higher risk. The nitrates are thought tobe converted to carcinogenic nitrites bybacteria Such bacteria may be introducedexogenously through the ingestion of partiallydecayed foods, which are consumed inabundance worldwide by the lowersocioeconomic classes.


Etiology

• Bacteria such as H. pylori may also contribute to this effect by causing chronic gastritis, loss of gastric acidity, and bacterial growth in the stomach.

• Loss of acidity may occur when acid-producing cells of the gastric antrum have been removed surgically to control benign peptic ulcer disease or when achlorhydria, atrophic gastritis, and even pernicious anemia develop in the elderly.


Etiology

• H. pylori has not been associated with the

diffuse, more proximal form of gastric

carcinoma .

• Individuals with blood group A have a

higher incidence of gastric cancer than

persons with blood group O; this

observation may be related to differences

in the mucous secretion, leading to altered

mucosal protection from carcinogens.（Dan L. Longo，2012）

Etiology

• A germ-line mutation in the E-cadherin gene

( CDH1 ), inherited in an autosomal

dominant pattern and coding for a cell

adhesion protein, has been linked to a high

incidence of occult diffuse-type gastric

cancers in young asymptomatic carriers.


Etiology

• In keeping with the stepwise model of

carcinogenesis, K-ras mutations appear to be

early events in intestinal-type gastric cancer.

• C-met expression is amplified in about 1 in 5

cases and correlates with advanced stage.


Etiology

• About half of intestinal-type tumors have

mutations in tumor suppressor genes such

as TP53

• Epigenetic changes (especially increased

methylation) has been correlated with

higher risk of invasive disease.

（Dan L. Longo，2012）A genetic model for colorectal tumorigenesis.

Clinical features

• Gastric cancers, when superficial and surgically curable, usually produce no symptoms. As the tumor becomes more extensive, patients may complain of an insidious upper abdominal discomfort varying in intensity from a vague, postprandial fullness to a severe, steady pain.

• Anorexia, often with slight nausea, is very common but is not the usual presenting complaint.


Clinical features

• Weight loss may eventually be observed,

and nausea and vomiting are particularly

prominent with tumors of the pylorus

• Dysphagia and early satiety may be the

major symptoms caused by diffuse lesions

originating in the cardia. （Dan L. Longo，2012）

Risk Factors for Gastric

Cancer• Definite—surveillance suggested

• Familial adenomatous polyposis

• Gastric adenomas

• Gastric biopsy revealing high-grade dysplasia

• Definite

• Chronic atrophic gastritis

• Gastric metaplasia or biopsy

• Helicobacter pylori infection

• Hereditary nonpolyposis colorectal cancer

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Risk Factors for Gastric

Cancer• Possible

• Excess alcohol ingestion

• Hamartomas

• High intake of salted, pickled, or smoked foods

• Low intake of fruits and vegetables

• Ménétrier’s disease

• Peutz-Jeghers syndrome

• Tobacco smoking

• Probable

• History of subtotal gastrectomy (> 20 years)

• Pernicious anemia

• Tobacco smoking (adenocarcinoma of cardia)



Diagnosis

• The initial diagnosis of gastric carcinoma

often is delayed because up to 80 percent

of patients are asymptomatic during the

early stages of stomach cancer.

• Unfortunately, in the United States, most

cases of gastric cancer are discovered

only after local invasion has advanced.



Diagnostic

• A double-contrast radiographic (barium)

examination is the simplest diagnostic

procedure for the evaluation of a patient

with epigastric complaints.

Courtesy of Norman Joffe, MD.Graphic 61767 Version 5.0


Diagnostic

• Endoscopy provides the most specific and

sensitive means of diagnosis of gastric

cancers. Gastrointestinal endoscopy

allows the physician to visualize and

biopsy the mucosa of the esophagus,

stomach, duodenum, and most of the

jejunum.

http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/stomach_canc

er.html

Diagnostic


TREATMENT

Gastric Adenocarcinoma• Complete surgical removal of the tumor

with resection of adjacent lymph nodes

offers the only chance for cure. However,

this is possible in less than a third of

patients. A subtotal gastrectomy is the

treatment of choice for patients with distal

carcinomas, while total or near-total

gastrectomies are required for more

proximal tumors.（Dan L. Longo，2012）

TREATMENT

Gastric Adenocarcinoma

http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/stomach_cancer.html

TREATMENT



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TREATMENT


• Gastric adenocarcinoma is a relatively

radioresistant tumor, and adequate control

of the primary tumor requires doses of

external beam irradiation that exceed the

tolerance of surrounding structures, such

as bowel mucosa and spinal cord.


TREATMENT

Gastric Adenocarcinoma• As a result, the major role of radiation

therapy in patients has been palliation of

pain. Radiation therapy alone after a

complete resection does not prolong

survival. In the setting of surgically

unresectable disease limited to the

epigastrium, patients treated with 3500–

4000 cGy did not live longer than similar

patients not receiving radiotherapy;（Dan L. Longo，2012）

TREATMENT

Gastric Adenocarcinoma• however, survival was prolonged slightly

when 5-fluorouracil (5-FU) plus leucovorin

was given in combination with radiation

therapy (3-year survival 50% vs 41% for

radiation therapy alone). In this clinical

setting, the 5-FU may be functioning as a

radiosensitizer.


TREATMENT

Gastric Adenocarcinoma• The administration of combinations of

cytotoxic drugs to patients with advanced

gastric carcinoma has been associated with

partial responses in 30–50% of cases;

responders appear to benefit from treatment.

• Such drug combinations have generally

included cisplatin combined with epirubicin or

docetaxel and infusional 5-FU, or with

irinotecan.


TREATMENT

Gastric Adenocarcinoma• Despite this encouraging response rate,

complete remissions are uncommon, the partial responses are transient, and the overall influence of multidrug therapy on survival has been unclear.

• However, combination chemotherapy administered before and after surgery as well as postoperative chemotherapy combined with radiation therapy reduces the recurrence rate and prolongs survival.


metastasis

• When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.

• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

• The metastatic tumor is the same type of cancer as the primary tumor. For example, if thyroid cancer spreads to the lung, the cancer cells in the lung are actually thyroid cancer cells. The disease is metastatic thyroid cancer, not lung cancer.

http://www.cancer.gov/cancertopics/pdq/treatment/unusual-cancers-childhood/patient/

Thanks for your attention

gastric cancer physio

Health & Medicine

development of gastric

lethal cancer

lung cancer

leading cause of cancer

percent of gastric cancers

incidence of diffuse

lowincidence nations

stomach cancers