Gastric cancer is one of the most common cancers worldwide. While rates have declined in recent decades, it remains the third leading cause of cancer death. Risk factors include H. pylori infection, smoking, and diets high in salted/pickled foods. Most cases are adenocarcinomas. Symptoms often do not appear until the cancer has spread. Treatment involves surgical removal of the tumor along with chemotherapy and radiation, but the outcomes remain poor as most cases are advanced at time of diagnosis.

1. Gastric Cancer
By: Saeid Afshar
(Ph.D. student of molecular medicine )
November 2014
Hamadan university of medical science
Molecular medicine and genetic department

2. 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/

3. 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 .
http://www.uptodate.com/

4. 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.
http://www.uptodate.com/

5. 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 .
http://www.uptodate.com/

6. • 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 .
http://www.uptodate.com/

7. GEOGRAPHICAL VARIATION
Geographical Variation in Gastric Cancer Incidence
Parkin DM. International variation. Oncogene 2004; 23: 6329-6340

8. 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）

9. • 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).
（Dan L. Longo，2012）

10. Pathology
• About 85% of stomach cancers are
adenocarcinomas, with 15% due to
lymphomas and gastrointestinal stromal
tumors (GIST) and leiomyosarcomas.
•
gastrointestinal stromal tumors Leiomyosarcoma
（Dan L. Longo，2012）

11. 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.
（Dan L. Longo，2012）

12. 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.
（Dan L. Longo，2012）

13. 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.
（Dan L. Longo，2012）

14. 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.
（Dan L. Longo，2012）

15. 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.

16. Etiology
• The long-term ingestion of high
concentrations of nitrates in dried, smoked,
and salted foods appears to be associated
with a higher risk. The nitrates are thought to
be converted to carcinogenic nitrites by
bacteria Such bacteria may be introduced
exogenously through the ingestion of partially
decayed foods, which are consumed in
abundance worldwide by the lower
socioeconomic classes.
（Dan L. Longo，2012）

17. 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.
（Dan L. Longo，2012）

18. 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）

19. 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.
（Dan L. Longo，2012）

20. 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.
（Dan L. Longo，2012）

21. 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.

23. 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.
（Dan L. Longo，2012）

24. 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）

25. 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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26. 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)
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27. 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.
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28. 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
（Dan L. Longo，2012）

29. 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

30. Diagnostic
（Dan L. Longo，2012）

31. Diagnostic
（Dan L. Longo，2012）

32. 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）

33. TREATMENT
Gastric Adenocarcinoma
http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/stomach_cancer.html

34. TREATMENT
Gastric Adenocarcinoma

35. TREATMENT
Gastric Adenocarcinoma
http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/stomach_canc
er.html

36. http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/stomach_canc
er.html

37. TREATMENT
Gastric Adenocarcinoma
• 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.
（Dan L. Longo，2012）

38. 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）

39. 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.
（Dan L. Longo，2012）

40. 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.
（Dan L. Longo，2012）

41. 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.
（Dan L. Longo，2012）

42. 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/

43. Thanks for your attention