GASTRIC Dr Lusine Harutyunyan

MALIGNANCIES
 DEFINITION

Stomach cancer, also known

as gastric cancer, is a cancer that
develops from the lining of
the stomach.
ANATOMY 1
The stomach begins at the gastroesophageal junction and ends at the duodenum. The stomach has
three parts: the uppermost part is the cardia; the middle and largest part is the body, or fundus; and
the distal portion, the pylorus, connects to the duodenum. These anatomic zones have distinct
histologic features. The cardia contains predominantly mucin-secreting cells. The fundus contains
mucoid cells, chief cells, and parietal cells. The pylorus is composed of mucus-producing cells and
endocrine cells.
The stomach wall is made up of five layers. From the lumen out, the layers are as follows:
•Mucosa
•Submucosa
•Muscularis
•Subserosa
•Serosa
ANATOMY 2
Externally, the peritoneum of the greater sac covers the anterior surface of the stomach.
A portion of the lesser sac drapes posteriorly over the stomach. The gastroesophageal
junction has limited or no serosal covering.
The right portion of the anterior gastric surface is adjacent to the left lobe of the liver
and the anterior abdominal wall. The left portion of the stomach is adjacent to the
spleen, the left adrenal gland, the superior portion of the left kidney, the ventral portion
of the pancreas, and the transverse colon.
The site of stomach cancer is classified on the basis of its relationship to the long axis of
the stomach. Approximately 40% of cancers develop in the lower part, 40% in the
middle part, and 15% in the upper part; 10% involve more than one part of the organ.
Most of the decrease in gastric cancer incidence and mortality in the United States has
involved cancer in the lower part of the stomach; the incidence of adenocarcinoma in the
cardia has actually shown a gradual increase.
EPIDEMIOLOGY
 6th most common cancer worldwide
 3rd most common cause of cancer-related death in the world
Although rates are low in North America and Northern Europe—in the United States, stomach malignancy
is currently the 15th most common cancer [2] —the disease remains difficult to cure in Western countries,
primarily because most patients present with advanced disease.
Decreases in gastric cancer have been attributed in part to widespread use of refrigeration, which has had
several beneficial effects: increased consumption of fresh fruits and vegetables; decreased intake of salt,
which had been used as a food preservative; and decreased contamination of food by carcinogenic
compounds arising from the decay of unrefrigerated meat products. Salt and salted foods may damage the
gastric mucosa, leading to inflammation and an associated increase in DNA synthesis and cell proliferation.
Other factors likely contributing to the decline in stomach cancer rates include lower rates of
chronic Helicobacter pylori infection, thanks to improved sanitation and use of antibiotics, and increased
screening in some countries.
The World Health Organization estimates that in 2018, gastric cancer accounted for 783,000 deaths
worldwide.
TYPES
CAUSES
Causes
Gastric cancer may often be multifactorial, involving both inherited predisposition and
environmental factors. Environmental factors implicated in the development of gastric cancer
include the following:
•Diet
•Helicobacter pylori infection
•Previous gastric surgery
•Pernicious anemia
•Adenomatous polyps
•Chronic atrophic gastritis
•Radiation exposure
DIET

A diet rich in pickled vegetables, salted

fish, salt, and smoked meats correlates with
an increased incidence of gastric cancer.
A diet that includes fruits and vegetables
rich in vitamin C may have a protective
effect.
 please check:
https://www.cancer.gov/publications/patien
t-education/eatinghints.pdf
SMOKING

Smoking is associated with an increased

incidence of stomach cancer in a dose-
dependent manner, both for number of
cigarettes and for duration of smoking.
Smoking increases the risk of cardiac and
noncardiac forms of stomach
cancer. [15] Cessation of smoking reduces the
risk. 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.
HELICOBACTER PYLORI
INFECTION 1
Chronic bacterial infection with H pylori is the strongest risk factor for stomach cancer.
H pylori may infect 50% of the world's population, but many fewer than 5% of infected individuals develop cancer.
It may be that only a particular strain of H pylori is strongly associated with malignancy, probably because it is
capable of producing the greatest amount of inflammation. In addition, full malignant transformation of affected
parts of the stomach may require that the human host have a particular genotype of interleukin (IL) to cause the
increased inflammation and an increased suppression of gastric acid secretion. For example, IL-17A and IL-17F are
inflammatory cytokines that play a critical role in inflammation. Wu et al found that carriage of IL-17F 7488GA and
GG genotypes were associated with an increased risk of gastric cancer.
H pylori infection is associated with chronic atrophic gastritis, and patients with a history of prolonged gastritis have
a sixfold increased 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.
A large-scale, long-term study from Korea—which along with China and Japan is a high-risk country for gastric
cancer—concluded that in patients with a family history of gastric cancer, treatment of H pylori infection more than
halves their risk of developing gastric cancer. In the study, which included 1676 patients ages 40 to 65 years with
confirmed H pylori infection and at least one first-degree relative with gastric cancer, patients were randomized to
triple antibiotic therapy or placebo and followed with surveillance endoscopy every 2 years.
Over a median follow-up of 9.2 years, gastric cancer developed in 1.2% of patients in the treatment group, versus
HELICOBACTER PYLORI
INFECTION 2
A study by Cheung et al found that risk of gastric cancer was increased in patients who
used proton pump inhibitors (PPIs) long-term after successful treatment for H
pylori infection. [21] In the study, which included 63,397 patients from a territory-wide
Hong Kong health database with a median follow-up of 7.6 years, PPIs use was associated
with more than a doubled risk of gastric cancer (hazard ratio [HR] 2.44; 95% confidence
index [CI], 1.42 to 4.20). The risk increased with duration of PPIs use, as follows:
•≥1 year - HR 5.04 (95% CI 1.23–20.61)
•≥2 years - HR 6.65 (95% CI 1.62–27.26)
•≥3 years - HR 8.34 (95% CI 2.02–34.41)
The relevance of this study to clinical practice remains uncertain, however, as the results
could be due to residual confounding or detection bias.
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.
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.
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. For example, germline truncating mutations of the E-
cadherin gene (CDH1) are detected in 50% of diffuse-type gastric cancers, and families that
harbor these mutations have an autosomal dominant pattern of inheritance with a very high
penetrance.
Other hereditary syndromes with a predisposition for stomach cancer include the following:
•Hereditary nonpolyposis colorectal cancer
•Li-Fraumeni syndrome
•Familial adenomatous polyposis
•Peutz-Jeghers syndrome
BISPHOSPHONATES

A large cohort study examined whether

use of oral bisphosphonates was
associated with an increased risk of
esophageal or gastric cancers. No
significant difference was observed for
increased risk of esophageal or gastric
cancers between the bisphosphonate
cohort and the control group.
OTHER CAUSES
•Infection with the Epstein-Barr virus may be associated with a rare (< 1%) form of
stomach cancer, lymphoepithelioma-like carcinoma.
•Pernicious anemia associated with advanced atrophic gastritis and intrinsic factor
deficiency is a risk factor for gastric carcinoma.
•Gastric cancer may develop in the remaining portion of the stomach following a
partial gastrectomy for gastric ulcer. Benign gastric ulcers may themselves develop
into malignancy.
•Obesity increases the risk of gastric cardia cancer.
•Radiation exposure: Survivors of atomic bomb blasts have had an increased rate of
stomach cancer. Other populations exposed to radiation may also have an increased
rate of stomach cancer.
DIAGNOSIS 1
Testing
The goal of obtaining laboratory studies is to assist in determining optimal therapy.
Potentially useful tests in patients with suspected gastric cancer include the
following:
•CBC: May be helpful to identify anemia, which may be caused by bleeding, liver
dysfunction, or poor nutrition; approximately 30% of patients have anemia
•Electrolyte panels
•Liver function tests
•Tumor markers such as CEA and CA 19-9: Elevated CEA in 45-50% of cases;
elevated CA 19-9 in about 20% of cases
DIAGNOSIS 2
Imaging studies
Imaging studies that aid in the diagnosis of gastric cancer in patients in whom the disease is
suggested clinically include the following:
•Esophagogastroduodenoscopy (EGD): To evaluate gastric wall and lymph node involvement
•Double-contrast upper GI 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
•Chest radiography: To evaluate for metastatic lesions
•CT scanning or MRI of the chest, abdomen, and pelvis: To assess the local disease process and
evaluate potential areas of spread
•Endoscopic ultrasonography (EUS): Staging tool for more precise preoperative assessment of the
tumor stage
DIAGNOSIS 3
Biopsy
Biopsy of any ulcerated lesion should include at least six specimens taken from around the lesion
because of variable malignant transformation. In selected cases, endoscopic ultrasonography may be
helpful in assessing depth of penetration of the tumor or involvement of adjacent structures.
Histologically, the frequency of different gastric malignancies is as follows [3] :
• Adenocarcinoma - 90-95%
• Lymphomas - 1-5%
• Gastrointestinal stromal tumors (formerly classified as either leiomyomas or leiomyosarcomas) - 2%
• Carcinoids - 1%
• Adenoacanthomas - 1%
• Squamous cell carcinomas - 1%
DIFFERENTIAL DIAGNOSIS
• Acute Gastritis
• Atrophic Gastritis
• Bacterial Gastroenteritis
• Chronic Gastritis
• Esophageal Cancer
• Esophageal Stricture
• Esophagitis
• Malignant Neoplasms of the Small Intestine
• Non-Hodgkin Lymphoma (NHL)
• Peptic Ulcer Disease
• Viral Gastroenteritis
 CLASSIFICATION

Please check: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418539/#:~:text=The%202010%20WHO%20classification

 CLINICAL PRESENTATION
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.
Signs and symptoms of gastric cancer include the following:
• Indigestion
• Nausea or vomiting
• Dysphagia
• Postprandial fullness
• Loss of appetite
• Melena or pallor from anemia
• Hematemesis
• Weight loss
• Palpable enlarged stomach with succussion splash
• Enlarged lymph nodes such as Virchow nodes (ie, left supraclavicular) and Irish node (anterior axillary)
PHYSICAL EXAMINATION
All physical signs are late events. By the time they develop, the disease is almost
invariably too far advanced for curative procedures.
Signs may include a palpable enlarged stomach with succussion splash; hepatomegaly;
periumbilical metastasis (Sister Mary Joseph nodule); and enlarged lymph nodes such
as Virchow nodes (ie, left supraclavicular) and Irish node (anterior axillary). Blumer
shelf (ie, shelflike tumor of the anterior rectal wall) may also be present. Some patients
experience weight loss, and others may present with melena or pallor from anemia.
Paraneoplastic syndromes such as dermatomyositis, acanthosis nigricans, and circinate
erythemas are poor prognostic features.
Other associated abnormalities include peripheral thrombophlebitis and
microangiopathic hemolytic anemia.
LABORATORY STUDIES
• Upper gastrointestinal (GI) tract endoscopy and biopsy
• Chest/abdomen/pelvic computed tomography (CT) with oral and intravenous contrast
• Positron emission tomography (PET) – CT evaluation if no evidence of M1 disease is found, and if
clinically indicated
• Complete blood cell count (CBC) and comprehensive chemistry profile
• Endoscopic ultrasound if no evidence of M1 disease is found
• Endoscopic resection for early-stage cancers
• Biopsy of metastatic disease as clinically indicated
• Microsatellite instability (MSI) and deficient mismatch repair (dMMR) testing if metastatic disease is
documented/suspected
• HER2-neu and programmed death ligand 1 (PD-L1) testing if metastatic adenocarcinoma is documented
or suspected
 TNM STAGING 1
The 2017 American Joint Committee on Cancer (AJCC) Cancer Staging Manual presents the following TNM
classification system for staging gastric carcinoma :
Primary tumor (T)
See the list below:
• TX - Primary tumor cannot be assessed
• T0 - No evidence of primary tumor
• Tis - Carcinoma in situ, intraepithelial tumor without invasion of lamina propria
• T1 - Tumor invades lamina propria, muscularis mucosae, or submucosa
• T1a - Tumor invades lamina propria or muscularis mucosae
• T1b - Tumor invades submucosa
• T2 - Tumor invades muscularis propria
• T3 - Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures
• T4 - Tumor invades serosa (visceral peritoneum) or adjacent structures
• T4a - Tumor invades serosa (visceral peritoneum)
TNM STAGING 2
Regional lymph nodes (N)
See the list below:
• NX - Regional lymph node(s) cannot be assessed
• N0 - No regional lymph node metastases
• N1 - Metastases in 1-2 regional lymph nodes
• N2 - Metastases in 3-6 regional lymph nodes
• N3 - Metastases in 7 or more regional lymph nodes
• N3a - Metastases in 7-15 regional lymph nodes
• N3b - Metastases in 16 or more regional lymph nodes
Distant metastasis
See the list below:
• M0 - No distant metastasis
CLINICAL STAGING
•Stage 0 - Tis, N0, M0
•Stage I - T1-2, N0, M0
•Stage IIA - T1-2, N1-3, M0
•Stage IIB - T3, N0, M0 or T4a, N0, M0
•Stage III - T3, N0, M0 or; T4a, N1-3, M0
•Stage IVA - T4b, any N, M0
•Stage IVB - Any T, any N, M1
 COMPLICATIONS
• Pathologic peritoneal and pleural effusions
• Obstruction of the gastric outlet, gastroesophageal junction, or small bowel
• Bleeding in the stomach from esophageal varices or at the anastomosis after surgery
• Intrahepatic jaundice caused by hepatomegaly
• Extrahepatic jaundice
• Inanition from starvation or cachexia of tumor origin
 Early postoperative complications include anastomotic failure, bleeding, ileus, transit failure at the
anastomosis, cholecystitis (often occult sepsis without localizing signs), pancreatitis, pulmonary infections,
and thromboembolism. Further surgery may be required for anastomotic leaks.
 Late mechanicophysiologic complications include dumping syndrome, vitamin B-12 deficiency, reflux
esophagitis, and bone disorders, especially osteoporosis.
 Postgastrectomy patients often are immunologically deficient, as measured by blastogenic and delayed
cutaneous hypersensitivity responses.
TREATMENT 1
Surgery
The surgical approach in gastric cancer depends on the location, size, and locally invasive
characteristics of the tumor.
Types of surgical intervention in gastric cancer include the following:
•Total gastrectomy, if required for negative margins
•Esophagogastrectomy for tumors of the cardia and gastroesophageal junction
•Subtotal gastrectomy for tumors of the distal stomach
•Lymph node dissection: Controversy exists regarding extent of dissection; the National
Comprehensive Cancer Network (NCCN) recommends D2 dissections over D1 dissections; a
pancreas- and spleen-preserving D2 lymphadenectomy provides greater staging information
and may provide a survival benefit while avoiding its excess morbidity when possible [4]
TREATMENT 2
Chemotherapy
Antineoplastic agents and combinations of agents used in managing gastric cancer include the following:
• Platinum-based combination chemotherapy: First-line regimens include epirubicin/cisplatin/5-FU or
docetaxel/cisplatin/5-FU; other regimens include irinotecan and cisplatin; other combinations include oxaliplatin and
irinotecan
• Trastuzumab in combination with cisplatin and capecitabine or 5-FU: For patients who have not received previous
treatment for metastatic disease
• Ramucirumab for the treatment of advanced stomach cancer or gastroesophageal (GE) junction adenocarcinoma in
patients with unresectable or metastatic disease following therapy with a fluoropyrimidine- or platinum-containing
regimen
• Pembrolizumab for gastric or GE junction carcinoma in patients expressing PD-L1 with disease progression on or
after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if
appropriate, HER2/neu-targeted therapy
• Trastuzumab deruxtecan for locally advanced or metastatic HER2-positive gastric or GE junction adenocarcinoma in
patients who have received a prior trastuzumab-based regimen
TREATMENT 3
Neoadjuvant, adjuvant, and palliative therapies
Potentially useful therapies in gastric cancer include the following:
• Neoadjuvant chemotherapy
• Intraoperative radiotherapy (IORT)
• Adjuvant chemotherapy (eg, 5-FU)
• Adjuvant radiotherapy
• Adjuvant chemoradiotherapy
• Palliative radiotherapy
• Palliative-intent procedures (eg, wide local excision, partial gastrectomy, total gastrectomy, simple
laparotomy, gastrointestinal anastomosis, bypass)
SURVIVAL RATES
•Stage IA - 94%
•Stage IB - 88%
•Stage IIA - 82%
•Stage IIB - 68%
•Stage IIIA - 54%
•Stage IIIB - 36%
•Stage IIIC - 18%
•Stage IV - 5%
Unfortunately, only a minority of patients with gastric cancer who undergo surgical resection
will be cured of their disease. Most patients have a recurrence.
PREVENTION
A diet that includes fruits and vegetables rich in
vitamin C may have a protective effect.

A review of eight trials by Rothwell et al found

allocation to aspirin reduced death caused by
cancer. A latent period of more than 5 years was
observed for stomach cancer.