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MINISTRY OF HEALTH OF UKRAINE
VINNITSA NATIONAL PIROGOV MEMORIAL MEDICAL
UNIVERSITY
"CONFIRM"
at the methodical meeting
Department of Ray diagnostics,
Ray therapy and Oncology
Head of the department
As. of Prof., M.S.D. Kostyuk A.G.
________________________
"______" ________ 2013 year
METHODICAL GUIDELINES
For self-study for students in preparing for the practical (seminary) lessons
Subject of Study
Oncology
Module No
1
Theme No
4
Topic of Lesson
Stomach cancer.
Risk factors. Classification by TNM. Methods of
diagnostics. Clinics. Treatment: surgery, radiotherapy,
chemotherapy, combined.
Course
5
Faculty
General Medicine
2
Topicality. Stomach cancer is uncommon before the age of 40 but thereafter
the incidence increases with age, reaching a peak between the ages of 60 and 65. For
some unknown reason, in most countries males are affected about two or three times
more commonly than females. In the past, cancer of the lower or middle stomach was
one of the more serious and more common cancers affecting mankind but
fortunately, over recent years, it has become less common. Stomach cancer has
distinct racial, geographic and dietary associations. It is about seven times more
common in Japan and Korea and three or four times more common in Eastern Europe
than in the US. Epidemiological studies suggest it has a direct close and relationship
to diet. People who have a diet that is high in animal fats, (especially chemically
preserved meats) and low in fresh fruit and vegetables have a greater risk of
developing stomach cancer. It may be related to a high intake of chemical food
preservatives and other methods of food preparation, curing, storage and
preservation. For example the high intake of smoked fi sh in Japan has been
incriminated. There is also a high incidence among people of northern Iceland who
eat large amounts of crude smoked fish as opposed to a lower incidence in the people
of southern Iceland who have a different diet. In Korea, the custom of eating a great
deal of red pepper and possibly other irritating spices in food is thought to be signifi
cant.
Learning Objectives:
1. Epidemiology of Stomach cancer.
2. Ethiology and Risk factors.
3. Differential diagnosis.
3. Morphology of Stomach cancer.
4. Classification TNM Stomach cancer.
5. Methods for obtaining of material for cytological and histological examination
6. Diagnostic of Stomach cancer
7. Treatment of Stomach cancer.
8. Types of surgical treatments.
9. Indications and contraindications for chemo- and radiotherapy.
10. Complication and adverse event of chemo- and radiotherapy
11. Survival and prognosis.
12. Follow-up.
13. Palliative care
3
Gastric cancer
Gastric cancer is the second most common cause of cancer-related death in the
world. Many Asian countries, including Korea, China, Taiwan, and Japan, have very
high rates of gastric cancer. Every year more then 21,000 new cases of gastric cancer
are diagnosed in the United States and 11,210 persons are dying of the stomach
cancer. The median age for gastric cancer in the United States is 70 years for males
and 74 years for females. Gastric cancer remains a difficult disease to cure in
Western countries, primarily because most patients present with advanced disease.
Even patients who present in the most favourable condition and who undergo
curative surgical resection often die of recurrent disease.
Gastric anatomy.
The stomach begins at the gastroesophageal junction and ends at the duodenum. The
stomach has 3 parts. The uppermost part of the stomach is the cardia, and the largest
and middle part is called the body.
The stomach wall is made up of 5 layers. From the lumen out, the layers include the
mucosa, the submucosa, the muscularis layer, the subserosal layer, and the serosal
layer. The peritoneum of the greater sac covers the anterior surface of the stomach.
The site of the cancer is classified on the basis of its relationship to the long axis of
the stomach. Approximately 40-50% of cancers develop in the lower part, 30-40% in
the middle part, and 15% in the upper part, and 10% involve more than one part of
the organ.
Frequency
United States
Gastric cancer is the seventh leading cause of cancer deaths. More than 22,000 new
cases are diagnosed each year, of which 11,430 are expected to die. In 2007, 21,260
new cases of gastric cancer (13,000 men; 8,260 women) will be diagnosed with
stomach cancer in the United States, and 11,210 persons (6,610 men; 4,600 women)
will die of the disease.
International
Adenocarcinoma of the stomach is the 4-th most common cancer worldwide.
Stomach cancer affected 850,000 people, of which 522,000 men and 328,000 women
died of stomach cancer. The highest death rates are recorded in Chile, Japan, South
America, and the former Soviet Union.
4
Mortality/Morbidity
The 5-year survival rate for curative surgical resection ranges from 30-50% for
patients with stage II disease and from 10-25% for patients with stage III disease.
Because these patients have a high likelihood of local and systemic relapse, some
physicians offer them adjuvant therapy. The operative mortality rate for patients
undergoing curative surgical resection at major academic centers is less than 3%.
Race
The rates of gastric cancer are higher in Asian and South American countries than in
the United States. Japan, Chile, and Venezuela have developed early screening
program that detects patients with early stage disease. These patients appear to do
quite well.
In the United States, Asian and Pacific Islander males and females have the highest
incidence of stomach cancer, followed by black, Hispanic, white, American Indian.
Sex
Gastric cancer affects slightly more men than women.
Age
Most patients are elderly at diagnosis. The median age for gastric cancer in the
United States is 70 years for males and 74 years for females. The gastric cancers that
occur in younger patients may represent a more aggressive variant.
Clinical
History

In the United States, about 25% of stomach cancer cases present with localized
disease, 31% present with regional disease, and 32% present with distant metastatic
disease;

Early disease has no associated symptoms; however, some patients with
incidental complaints are diagnosed with early gastric cancer. Most symptoms of
gastric cancer reflect advanced disease. Patients may complain of indigestion, nausea
or vomiting, dysphagia, postprandial fullness, loss of appetite, anaemia, melena,
hematemesis, and weight loss.

Late complications include ascites; pilorostenosis, diphagia; bleeding;
intrahepatic jaundice caused by hepatic metastases; cachexia of tumor origin.
5
Physical

All physical signs are late events, and almost invariably the signs develop too
late for curative procedures.

Signs may include a palpable enlarged stomach; hepatomegaly; periumbilical
metastasis (Sister Mary Joseph nodule); and enlarged lymph nodes such as the
following: Virchow nodes (ie, left supraclavicular) and Irish node (anterior
axillary). Some patients have weight loss and others may present with melena
or pallor from anemia.

Paraneoplastic syndromes such as dermatomyositis, acanthosis nigricans are
poor prognostic features.

Other associated abnormalities also include peripheral thrombophlebitis and
microangiopathic hemolytic anemia.
Causes
Several factors are implicated in the development of gastric cancer, including diet,
Helicobacter pylori infection, previous gastric surgery, pernicious anemia,
adenomatous polyps, chronic atrophic gastritis, prior radiation exposure or inherited
syndromes. Gastric cancer may often be multifactorial involving both inherited
predisposition and environmental factors.

Diet
A diet rich in pickled vegetables, salted fish, excessive dietary salt, and
smoked meats correlates with an increased incidence of gastric cancer.
o
A diet that includes fruits and vegetables rich in vitamin C may have a
protective effect.
o

Smoking
Smoking is associated with an increased incidence of stomach cancer in
a dose-dependent manner, both for number of cigarettes and duration of smoking.
o
Smoking increases the risk of cardiac and noncardiac forms of stomach
cancer. Cessation of smoking reduces the risk.
o
A meta-analysis of 40 studies estimated that the risk was increased by
approximately 1.5- to 1.6-fold and was higher in men.
o

Helicobacter pylori infection
Chronic bacterial infection with H pylori is the strongest risk factor for
stomach cancer.
o
6
H pylori may infect 50% of the world's population, but much less than
5% of infected individuals develop cancer. It may be that only a particular strain of H
pylori, one of which is capable of producing the greatest amount of inflammation, is
especially associated with the risk of malignancy.
o
H pylori infection is associated with chronic atrophic gastritis, and
patients with a history of prolonged gastritis have a 6-fold increase in their risk of
developing gastric cancer. Interestingly, this association is particularly strong for
tumors located in the antrum, body, and fundus of the stomach but does not seem to
hold for tumors originating in the cardia.
o

Previous gastric surgery
Previous surgery is implicated as a risk factor. The rationale is that
surgery alters the normal pH of the stomach, which may in turn lead to metaplastic
and dysplastic changes in luminal cells.
o
Retrospective studies demonstrate that a small percentage of patients
who undergo gastric polyp removal have evidence of invasive carcinoma within the
polyp. This discovery has led some researchers to conclude that polyps might
represent premalignant conditions.
o

o
Genetic factors
Some 10% of stomach cancer cases are familial in origin.
Genetic factors involved in gastric cancer remain poorly understood,
though specific mutations have been identified in a subset of gastric cancer patients.
Other hereditary syndromes with a predisposition for stomach cancer include
hereditary nonpolyposis colorectal cancer, Li-Fraumeni syndrome, familial
adenomatous polyposis, and Peutz-Jeghers syndrome.
o
Ebstein-Barr virus: The Epstein-Barr virus may be associated with an
unusual form of stomach cancer (<1%), lymphoepithelioma like carcinoma.
o
Pernicious anemia: Pernicious anemia associated with advanced
atrophic gastritis and is a risk factor for gastric carcinoma.
o

Gastric ulcers
Gastric cancer may develop in the remaining portion of the stomach
following a partial gastrectomy for gastric ulcer.
o
o

Benign gastric ulcers may develop into malignancy.
Obesity: Obesity increases the risk of gastric cardiac cancer.
7

Radiation exposure: Atomic bomb survivors exposed to radiation have had an
increased risk of stomach cancer. Other populations exposed to radiation may also
have an increased risk of stomach cancer.
Laboratory Studies

Carcinoembryonic antigen (CEA) is increased in 45-50% of cases.

Cancer antigen (CA) 19-9 is elevated in about 20% of cases.
Imaging Studies

Esophagogastroduodenoscopy has a diagnostic accuracy of 95%.
o
This relatively safe and simple procedure provides a permanent color
photographic record of the lesion.
o
This procedure is also the primary method for obtaining a tissue
diagnosis of suspected lesions. Biopsy of any ulcerated lesion should
require at least 6 biopsies taken from around the lesion because of
variable malignant transformation.
o
In selected cases, endoscopic ultrasound may be helpful in assessing
depth of penetration of the tumor or involvement of adjacent structures.

Double-contrast upper gastrointestinal series and barium swallows may be
helpful in delineating the extent of disease when obstructive symptoms are
present or when bulky proximal tumors prevent passage of the endoscope to
examine the stomach distal to an obstruction (more common with
gastroesophageal [GE]-junction tumors). These studies are only 75% accurate
and should for the most part be used only when upper GI endoscopy is not
feasible.

Chest radiograph is done to evaluate for metastatic lesions.

CT scan or MRI of the chest, abdomen, and pelvis assess the local disease
process as well as evaluate potential areas of spread (ie, enlarged lymph nodes,
possible liver metastases).

Endoscopic ultrasound allows for a more precise preoperative assessment of
the tumor stage.
Histologic Findings
Adenocarcinoma of the stomach constitutes 90-95% of all gastric malignancies. The
second most common gastric malignancies are lymphomas. Gastrointestinal stromal
tumors formerly classified as either leiomyomas or leiomyosarcomas account for 2%
8
of gastric neoplasms. Carcinoids (1%), adenoacanthomas (1%), and squamous cell
carcinomas (1%).

Adenocarcinoma of the stomach is subclassified according to histologic
description as follows: tubular, papillary, mucinous, or signet-ring cells, and
undifferentiated lesions.

Macroscopic types are also classified by gross appearance: polypoid (exophit
Forms) ,ulcerative (mesofit), nfiltrative (diffuse linitis plastica), superficial
spreading, multicentric,

Researchers also employ a variety of other classification schemes. The Lauren
system classifies gastric cancer pathology as either Type I (intestinal) or Type
II (diffuse). An appealing feature of classifying patients according to the
Lauren system is that the descriptive pathologic entities have clinically
relevant differences.
Staging
The 2006 American Joint Committee on Cancer (AJCC) Cancer Staging Manual
presents the following TNM classification system for staging gastric carcinoma:

Spread patterns
o
Cancer of the stomach can spread directly, via lymphatics, or
hematogenously.
o
Direct extension into the omentum, pancreas, diaphragm, transverse
colon or mesocolon, and duodenum is common.
o
The abundant lymphatic channels within the submucosal and subserosal
layers of the gastric wall allow for easy microscopic spread.
o
Lymphatic drainage is through numerous pathways and can involve
multiple nodal groups (eg, gastric, gastroepiploic, celiac, porta hepatic,
splenic, suprapancreatic, pancreaticoduodenal, paraesophageal, and
paraaortic lymph nodes).
o
The cancer also spreads hematogenously, and liver metastases are
common.
Surgical Care

Type of surgery
9

o
In general, most surgeons perform a total gastrectomy, an
esophagogastrectomy for tumors of the cardia and gastroesophageal
junction, and a subtotal gastrectomy for tumors of the distal stomach.
o
A randomized trial comparing subtotal with total gastrectomy for distal
gastric cancer revealed similar morbidity, mortality, and 5-year survival
rates.
o
Because of the extensive lymphatic network around the stomach and the
propensity for this tumor to extend microscopically, traditional teaching
is to attempt to maintain a 5-cm surgical margin proximally and distally
to the primary lesion.
Lymph node dissection
The extent of lymph node dissection is defined by the designation D. A D1
dissection includes just the perigastric lymph nodes. A classic D2 dissection also
includes nodes along the hepatic, left gastric, celiac, and splenic arteries as well as
those in the splenic hilum. Dissections which include nodes along the porta
hepatis, retropancreatic, and periaortic regions are classified as D3.
 Outcome
o
The 5-year survival rate for a curative surgical resection ranges from 6090% for patients with stage I, 30-50% for patients with stage II disease,
and 10-25% for patients with stage III disease.
o
Because these patients have a high likelihood of local and systemic
relapse, some physicians offer adjuvant therapy.
Deterrence/Prevention
A diet that includes fruits and vegetables rich in vitamin C may have a protective
effect.
Prognosis

Unfortunately, only a minority of patients with gastric cancer who undergo a
surgical resection will be cured of their disease. The majority of patients have
a recurrence.

Adjuvant therapy: The pattern of failure prompted a number of investigations
into adjuvant therapy. The rationale behind radiotherapy is to provide
additional local-regional tumor control. Adjuvant chemotherapy is used either
as a radiosensitizer or as definitive treatment for presumed systemic
metastases.
o
Adjuvant radiotherapy
10

o

Moertel and colleagues randomized postoperative patients with
advanced gastric cancer to receive 40 Gray (Gy) of radiotherapy
or 40 Gy of radiotherapy with 5-FU as a radiosensitizer and
demonstrated improved survival associated with the combined
modality therapy.
Adjuvant chemotherapy
Numerous randomized clinical trials comparing combination chemotherapy in the
postoperative setting to surgery alone did not demonstrate a consistent survival
benefit.
A European randomized trial also demonstrated survival benefit when patients
were treated with 3 cycles of preoperative chemotherapy (epirubicin, cisplatin, and 5fluorouracil) followed by surgery and then 3 cycles of postoperative chemotherapy
compared with surgery alone. The benefit was comparable to that obtained with
postoperative chemoradiation in the US trial. However, the Gastric Chemotherapy
Group for Japan did not demonstrate a significant survival benefit with neoadjuvant
chemotherapy.

o
Platinum-based chemotherapy in combinations such as epirubicin/cisplatin/5FU or docetaxel/cisplatin/5-FU represents the current first-line chemotherapies.
Other active regimens include irinotecan and cisplatin and other combinations
with oxaliplatin and irinotecan.
o
Bevacizumab, a monoclonal antibody against vascular endothelial growth
factor (VEGF) is currently being evaluated for use in advanced gastric cancer.
Suggested Reading:
1. Manual Of Clinical Oncology, - Dennis A. Casciato, Barry B. Lowitz, 2000
2. Oxford Handbook of Oncology, - Oxford University Press, 2002
3. Basics of Oncology, - Frederick O. Stephens · Karl R. Aigner, 2009
4. HARRISON’S Manual of Oncology, - Bruce A. Chabner, Thomas J. Lynch,
Jr., Dan L. Longo, 2008