Description
Gastric carcinoma, also known as stomach cancer, is a malignant tumour originating from the lining of the stomach and commonly located in the pyloric antrum. It is a significant cause of cancer-related morbidity and mortality globally. Despite advances in diagnosis and treatment, the prognosis for gastric cancer remains poor, particularly in advanced stages.
Pathogenesis
Gastric carcinomas may arise via several pathogenic mechanisms, but the majority are thought to develop through a multistep process of gastric mucosal changes. This starts from chronic gastritis, often due to Helicobacter pylori infection, progressing to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually invasive cancer.
Subtypes
Gastric carcinoma can be categorised into two main histological subtypes:
- Intestinal type (most common, 70%): Characterised by cohesive cells that form gland-like tubular structures. It is associated with H. pylori infection, dietary factors, smoking, and chronic gastritis.
- Diffuse type (30%): Characterised by poorly cohesive, signet ring cells that do not form glandular structures. These tumours are often more aggressive and are associated with a worse prognosis.
Epidemiology, Risk Factors & Associations
Gastric cancer is the third leading cause of cancer-related death worldwide, with the highest incidence in Eastern Asia, Eastern Europe, and South America. Males are affected twice as often as females. Age is a significant risk factor, with most patients diagnosed over the age of 60.
Risk factors and associations include:
- Helicobacter pylori infection: Strongest known risk factor, involved in approximately 75% of all gastric cancers
- Dietary factors: High intake of nitrites and nitrates (salted, smoked, or poorly preserved foods), and low intake of fruits and vegetables
- Smoking: Doubles the risk of gastric cancer
- Pernicious anaemia, chronic atrophic gastritis, and gastric polyps
- Genetic factors: Certain inherited conditions such as hereditary diffuse gastric cancer and familial adenomatous polyposis increase the risk.
Clinical Features
Patients may present with non-specific symptoms such as dyspepsia, early satiety, weight loss, abdominal pain, nausea, or vomiting. Haematemesis or melena, may indicate advanced disease or complications. Palpable abdominal mass, ascites, or lymphadenopathy may be noted on physical exam. Lymphatics spread
may reveal left supraclavicular adenopathy. There may be enlarged ovary (Krukenberg’s tumour) by peritoneal spread.
Complications
Complications of gastric cancer include gastric outlet obstruction, perforation, bleeding, and metastasis. The most common sites of metastasis are the liver, peritoneum, and lymph nodes.
Subtypes
Gastric carcinomas can also be classified according to their location in the stomach (proximal, middle, distal), their macroscopic appearance (polypoid, fungating, ulcerated, diffusely infiltrative), and the Lauren classification (intestinal, diffuse, and mixed types).
Pathological Features
Histopathology
Histologically, gastric carcinomas can be classified into two main types according to the Lauren classification:
- Intestinal type: Tumour cells are cohesive and form gland-like structures. Often there is an inflammatory reaction in the stroma.
- Diffuse type: Characterised by poorly cohesive cells, often with a signet-ring appearance. They infiltrate the stroma in a scattered manner, leading to thickening of the gastric wall (“linitis plastica“).
Genetics
The most common genetic alterations in gastric cancer involve TP53, HER2/neu, and CDH1 genes. A subset of gastric cancers is associated with microsatellite instability.
Biochemistry
Several tumour markers may be elevated in gastric cancer, including carcinoembryonic antigen (CEA) and CA19-9, but they are not specific for the disease.
Radiological Features
General Features
- Typically appears as an irregular thickening of the gastric wall, though its appearance can vary.
- Early-stage disease may only show subtle mucosal abnormalities
- Advanced stages can exhibit significant wall thickening, a mass, or an ulcerative lesion.
- The lesion can be anywhere within the stomach, but is most commonly found in the antrum or the lesser curvature of the stomach.
Features suggestive of advanced disease or complications include:
- Direct invasion into adjacent organs (pancreas, liver, colon, or anterior abdominal wall)
- Distant metastases (most commonly to the liver, peritoneum, and distant lymph nodes)
- Lymphadenopathy, especially along the lesser curvature, left gastric artery, coeliac axis, and hepatoduodenal ligament
- Gastric outlet or bowel obstruction
- Ascites or peritoneal nodularity suggestive of peritoneal carcinomatosis
CT
- Thickening of the gastric wall
- Enhancement of the tumour, usually less than that of normal gastric mucosa
- Enlarged regional lymph nodes
- Direct invasion into adjacent organs or metastatic disease.
MRI
- T1WI: Typically appears as a low-signal-intensity mass relative to the high signal intensity of the gastric wall.
- T2WI: The tumour appears as a high-signal-intensity mass, often with heterogeneity due to necrosis or mucin production.
- •C+ (Gadolinium-enhanced): The tumour shows early and persistent enhancement.
- DWI/ADC: Restricted diffusion within the tumour is noted due to high cellularity.
- Fat-suppressed T1-weighted images: Useful in detecting peritoneal or omental metastasis, which show up as high-signal-intensity lesions.
Fluoroscopy
- On barium studies, gastric carcinoma may appear as an irregular ulcer, a mass, or diffuse thickening of the gastric wall which does not demonstrate normal peristalsis. The presence of an irregular, nodular, or destroyed gastric mucosal pattern is suggestive.
PET
- FDG-PET can be used in the detection of distant metastases, recurrence after treatment, and to monitor the response to therapy.
EUS
- Particularly useful for assessing the depth of invasion (T stage) and the involvement of regional lymph nodes (N stage).
Grading and Staging
The grade of gastric carcinoma is based on its degree of differentiation. The staging of gastric carcinoma is typically done using the TNM system from the American Joint Committee on Cancer.
Differential Diagnosis
- Gastric lymphoma: May present with similar clinical and imaging findings. Endoscopic biopsy and immunohistochemical staining are usually necessary for differentiation.
- Gastric GIST: Typically appears as a submucosal mass with non-specific enhancement on CT.
- Gastric polyps or hyperplastic gastric folds: May be differentiated based on typical benign features and lack of malignant characteristics such as irregular borders or deep ulceration.
- Gastric metastasis: Consider in patients with a known primary malignancy elsewhere.
Management
- The mainstay of gastric cancer treatment is surgery, which may be preceded or followed by chemotherapy or chemoradiation. Decisions regarding management are typically made in a multidisciplinary setting.
- A tissue biopsy obtained either through endoscopy or during surgery is crucial for definitive diagnosis and further management planning.