Cancer: Introduction, Pathology, Epidemiology
Dimitrios H. Roukos, MD, Niki
J. Agnantis, MD, Michael Fatouros, MD, and Angelos M. Kappas,
From the Departments of Surgery (DHR, MF, AMK) and Pathology
(NJA), Ioannina University School of Medicine, 45110 Ioannina,
Gastric carcinoma is a malignant disease, which
starts in the stomach. Despite declining incidence still remains
the second cause of death of all malignancies worldwide. It
is a major health problem for two reasons: In Asia, East Europe
and developing countries the incidence decreases slowly. In
USA and West Europe although incidence decreases sharply, mortality
of diagnosed gastric cancer remains high.[1-4]
Adenocarcinoma of the stomach still remains a major health problem.
There has been an decrease in incidence of this cancer worldwide
but the degree of this reduction varies considerably among different
1. In USA
and West Europe gastric cancer decreases dramatically in the
last 50 years. In USA only 21,700 new gastric cancer cases are
expected in 2001. However, despite advances in research and
current treatment improvements, mortality of diagnosed gastric
cancer remains very high.
2. In China (1,3 billion population), Japan, Korea and other
East countries the decrease in incidence is much slowly and
gastric cancer remains one of the most common malignancy and
a leading cause of death from cancer.
3. In developing
countries the decrease in incidence is also slow.[1-4]
The world's population is expected to increase from the current
6.1 billion to 9.3 billion during the next 50 years (United
Nations Population Division) with Africa and Asia experiencing
the greatest population growth. Since gastric cancer decreases
there slowly, is expected an increased number of new cases in
developing countries and Asia. The challenge of controlling
the disease in these areas can not obviously resolved by endoscopic
screening for early detection or sophisticated staging with
subsequent tailored multidisciplinary approach which appear
completely unrealistic now or in the near future. A rethinking
about effective management strategy of the disease is needed.
The stomach is a sack-like organ between esophagus (a tube-shaped
organ that carries food through the neck and chest to the stomach)
and duodenum (first part of the small intestine). The stomach
holds food and mixed it by secreting gastric juice into a thick
fluid called chyme, which is then emptied into the duodenum.
The stomach is divided into three different sections. The upper
third, proximal stomach, closed to the esophagus is consisted
of gastroesophageal junction (cardia) and fundus, the middle
third of the stomach, the body and the lower portion (closed
to the intestine) is the distal stomach consisted of the antrum
and pylorus. Pylorus acts as a valve to control emptying of
the stomach contents into the duodenum. The stomach wall includes
from the inner to out lining 4 layers, the mucosa, submucosa,
muscularis propria, subserosa and serosa). The stomach has two
curves, the lesser and greater curves, in which is attached
the lesser and greater omentum respectively. Other organs next
to the stomach, apart of esophagus and duodenum, are the colon,
liver, spleen, and pancreas.
How does gastric carcinoma grow and spread?
Cells divided, grow and accumulated form tumors. Both benign
and malignant tumors grow in an uncontrolled way. But it is
only cells of malignant tumors that invade surrounding tissues,
travel in blood and lymphatic systems and home into distant
organs where they form secondary tumors (metastasis).[5-6]
Malignant primary gastric cancer cells at first confined into
the mucosal layer (intra-mucosal cancers) and after a rather
long natural history progress infiltrating the other layers
of the wall stepwise (submucosa, muscularis propria, subserosa,
serosa). When at diagnosis the cancer invasion is confined to
mucosa or submucosal layer is defined as early gastric cancer
(EGC), whereas invasion into muscularis propria or beyond it
is defined as advanced gastric cancer (AGC). If stomach cancers
left untreated, can spread and disseminate in a variety of forms:
Through serosa infiltrating the adjacent organs (T4-cancers:
spleen, transverse colon, liver, pancreas, etc)
Due cancer cells which exfoliated from tumors penetrated serosal
surface of the stomach (T3, T4-cancers). These cells may implant
and proliferate in peritoneal surface cavity leading to peritoneal
Due cancer cells that released from the original tumor and enter
the lymphatic or blood circulation, migrate and form seconadary
tumors (metastasis) in distant target-organs (liver, lung) and
The term gastric cancer or gastric carcinoma refers to adenocarcinoma
of the stomach that accounts for around 90% of all stomach malignant
tumors. The remainder malignant lesions of the stomach are gastric
lymphomas (about 2%-7%) which in majority of cases are lymphoma
of mucosa-associated lymphoid tissue (MALT-concept) and other
rare tumors sush as gastric stromal tumors (sarcomas) developed
from the muscle or connective tissue of the stomach wall, and
EPIDEMIOLOGY AND BIOLOGY
The incidence of gastric adenocarcinoma decreases worldwide.[1-4,8,9]
There have however been major geographical differences even
among different areas in the same country. The incidence decreases
dramatically in USA and many western European countries but
much more slowly in far East (China, Japan, Korea), South America
(Kolombia. Puerto Rico), Central Europe (Poland) and developing
contries. In the USA, gastric cancer decreases now 1.4% per
year and it is now only one-fourth (21700 new cases are expected
in 2001 [1:www.cancer.org]) as common as it was in 1930.[1,3,9]
Why does gastric cancer incidence decrease?
The reasons for the decreased incidence of gastric cancer have
not been elucidated. As possible factors have been reported
a decreased consumption of salt-preserved foods and an increased
consumption of fresh fruits and vegetables after the widespread
introduction of refrigeration.[4-9]
Does declining incidence of gastric adenocarcinoma related
to the sub-site (cardia/non-cardia)?
The declining incidence of gastric cancer in the USA and Western
Europe largely reflects a decline in distal lesions, whereas,
in contrast, there has been a steady rise in the incidence of
adenocarcinoma of the proximal stomach and the gastroesophageal
junction in the USA and Europe.[9-11] However, more recent data
from Sweden indicate an overall decline in incidence of cancers
distal to the gastric cardia by 9% [95% CI 6-12%] per year),
but did not confirm a rise of cardia cancer which has been remained
Gastric adenocarcinoma is classified according to WHO (adenocarcinoma,
signet ring-cell carcinoma and undifferentiated carcinoma) but
in the last years the Lauren-classification into two major
subtypes (intestinal type and diffuse type carcinomas) is now
predominantly used worldwide.
The histological classification of gastric carcinoma into the
intestinal type and diffuse type is based on the criteria proposed
by Lauren. The proportion of intestinal type accounts for
approximately 50%, that of the diffuse type 35% and the remainder
15% is characterized as ''unclassifie'' or mixed type cancer.[13-16]
The intestinal type is characterized by cohesive neoplastic
cells forming glandlike tubular structures, whereas in diffuse
type cell cohesion is absent, so that individual cells infiltrate
and thicken the stomach wall without forming a discrete mass.
This difference in microscopic growth pattern is also reflected
in the different macroscopic appearance of the two histological
subtypes. Whereas for intestinal type the macroscopic margins
correspond approximately to the microscopic spread, the diffuse
type as a poorly differentiated cancer can extend submucosally
far beyond its macroscopic borders. This difference in tumor
spread of the two types of Lauren-classification is of clinical
importance in decision-making about appropriate treatment option.
The intestinal type predominate in high-risk areas, occur more
often in distal stomach, and is often preceded by a prolonged
precancerous phase, whereas diffuse tumors prevail among young
patients and women and the contribution of hereditary factors
to their causation is higher.
WORLD Health Organization (WHO) - and Lauren-classification:
How to combine?
reports now the WHO-classification is used while in some others
the histologic classification according to the Lauren. Thus,
there is confusion among phycisians. It is therefore useful
and of practical value to see whether these two classifications
systems can easily and simply be combined. Indeed, in general,
well and moderately differentiated cancer of WHO correspond
to intestinal type according to Lauren, whereas poor differentiated
or undifferentiated or signet ring cell -carcinoma to the diffuse
type carcinoma respectively.
Is there a difference in time trends incidence of the
two histologic sub-types?
The decline in overall incidence of gastric carcinoma during
this century appears to be largely attributable to a decrease
of the intestinal-type lesions, while the occurrence of diffuse
type is thought to have remained more stable.[9,14,15] Most
recent epidemiological data from North Europe (Sweden) however,
indicate that both types decline markedly, at similar rapidity,
and with no significant trend differences between the intestinal
and diffuse types.
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