Gastric cancer is a malignant tumour arising from the epithelial lining of the stomach. It is one of the major gastrointestinal malignancies and remains a significant cause of cancer-related morbidity and mortality worldwide.

Gastric cancer is frequently diagnosed at an advanced stage because early disease is often asymptomatic or presents with non-specific gastrointestinal symptoms. Late presentation contributes to poor prognosis, especially in patients with locally advanced or metastatic disease.

Approximately 90–95% of gastric cancers are adenocarcinomas, arising from gastric mucosal glandular cells. Other less common gastric malignancies include gastric lymphoma, gastrointestinal stromal tumours (GIST), and neuroendocrine tumours.

Management depends on tumour stage, histological subtype, molecular characteristics, and patient performance status. Curative treatment requires a multidisciplinary approach involving surgery, chemotherapy, radiotherapy, targeted therapy, and supportive care.

Epidemiology

Gastric cancer remains one of the most common cancers globally, with geographical variation in incidence.

• It is more common in males than females.

• Incidence increases with advancing age.

• Most cases occur after the age of 50 years.

• Gastric adenocarcinoma accounts for approximately 90–95% of gastric malignancies.

The disease burden is higher in regions with:

• High prevalence of Helicobacter pylori infection.

• Dietary exposure to smoked and salt-preserved foods.

• Limited access to early diagnostic services.

In Tanzania, gastric cancer contributes significantly to gastrointestinal cancer burden and commonly presents at an advanced stage, requiring referral to specialized oncology centres.

Risk factors

Risk factors for gastric cancer include environmental, infectious, genetic, and lifestyle-related factors.

1. Age

• Risk increases progressively with advancing age.

• Most cases occur among older adults.

2. Gender

• Gastric cancer is more common in males.

3. Helicobacter pylori infection

Chronic infection with H. pylori causes:

• Chronic gastritis.

• Gastric mucosal atrophy.

• Intestinal metaplasia.

• Dysplasia.

• Gastric adenocarcinoma.

4. Epstein–Barr virus (EBV)

• Associated with a subset of gastric cancers.

• Causes molecular changes promoting malignant transformation.

5. Dietary factors

Increased risk is associated with:

• Smoked foods.

• Salt-preserved foods.

• High intake of processed foods.

Protective factors include:

• Adequate intake of fresh fruits and vegetables.

6. Tobacco smoking

Smoking increases the risk of gastric cancer through chronic exposure to carcinogenic substances.

7. Genetic factors

Associated conditions include:

• Familial gastric cancer.

• Hereditary diffuse gastric cancer syndrome.

• Familial adenomatous polyposis.

• Lynch syndrome.

8. Premalignant gastric conditions

• Chronic atrophic gastritis.

• Gastric intestinal metaplasia.

• Gastric adenomas.

• Previous partial gastrectomy.

Pathophysiology

Gastric cancer develops through progressive genetic and cellular changes causing uncontrolled growth of gastric epithelial cells.

The common pathway for intestinal-type gastric adenocarcinoma includes:

1. Chronic gastric mucosal inflammation.

2. Gastric atrophy.

3. Intestinal metaplasia.

4. Dysplasia.

5. Invasive carcinoma.

H. pylori infection plays a major role by causing persistent inflammation and DNA damage.

Tumour progression occurs through:

• Local invasion into gastric wall layers.

• Lymphatic spread to regional lymph nodes.

• Hematogenous spread to distant organs.

Common metastatic sites include:

• Liver.

• Peritoneum.

• Lung.

• Bone.

Clinical presentation

Clinical presentation varies depending on tumour location, stage, and presence of metastases.

Early gastric cancer may cause minimal symptoms, resulting in delayed diagnosis.

Advanced disease commonly presents with:

• Progressive gastrointestinal symptoms.

• Weight loss.

• Malnutrition.

• Features of gastric outlet obstruction or bleeding.

Symptoms

Upper gastrointestinal symptoms

Epigastric pain

• Common presenting symptom.

• May worsen with food intake.

Early satiety

• Feeling full after eating a small amount of food.

• Suggests reduced gastric capacity due to tumour infiltration.

Dyspepsia

• Persistent indigestion.

• Bloating.

• Abdominal discomfort.

Nausea and vomiting

May occur due to obstruction, especially with distal gastric tumours.

Symptoms due to obstruction

Distal gastric tumours may cause:

• Persistent vomiting.

• Difficulty with food passage.

• Abdominal fullness.

Symptoms due to bleeding

Gastric cancer may cause:

• Occult gastrointestinal bleeding.

• Melena.

• Haematemesis (less common).

Symptoms due to advanced disease

• Unintentional weight loss.

• Loss of appetite.

• Fatigue.

• General weakness.

Clinical signs

Clinical examination findings may include:

General signs

• Pallor due to chronic blood loss.

• Cachexia.

• Poor nutritional status.

Abdominal findings

• Epigastric mass.

• Abdominal tenderness.

• Hepatomegaly due to liver metastases.

Signs of metastatic disease

Virchow node

• Left supraclavicular lymph node enlargement.

Sister Mary Joseph nodule

• Periumbilical metastatic lymph node.

Other findings

• Ascites due to peritoneal spread.

Differential diagnosis

Differential diagnoses of gastric cancer include:

• Peptic ulcer disease.

• Chronic gastritis.

• Gastric polyp.

• Gastric lymphoma.

• Gastrointestinal stromal tumour (GIST).

• Pancreatic malignancy.

• Gallbladder disease.

• Functional dyspepsia.

Diagnostic criteria

Diagnosis should be suspected in patients presenting with:

• Persistent epigastric pain.

• Epigastric pain worsened by food intake.

• Early satiety.

• Unexplained weight loss.

• Gastrointestinal bleeding.

• Palpable epigastric mass.

• Features of gastric outlet obstruction.

Definitive diagnosis requires:

• Upper gastrointestinal endoscopy.

• Biopsy demonstrating malignant histology.

Investigations

Laboratory investigations

Full blood count (FBC)

Used to assess:

• Anaemia due to chronic gastrointestinal bleeding.

• Baseline treatment status.

Liver function tests (LFTs)

Assess:

• Liver involvement.

• Baseline chemotherapy suitability.

Renal function tests

Includes:

• Urea.

• Creatinine.

Important before chemotherapy, particularly cisplatin-based regimens.

Stool occult blood test

Used to detect:

• Hidden gastrointestinal bleeding.

Tumour markers

Carcinoembryonic antigen (CEA)

• May be elevated in gastric cancer.

• Useful mainly for monitoring response and recurrence.

HER2 testing

Immunohistochemistry (IHC) for HER2 status

Used to identify patients eligible for targeted therapy with trastuzumab.

Imaging investigations

Chest X-ray (CXR)

Used for:

• Baseline assessment.

• Detection of pulmonary metastases.

Double contrast barium meal

May demonstrate:

• Gastric filling defects.

• Irregular mucosal patterns.

• Obstruction.

CT scan of abdomen and pelvis

Used for staging:

• Primary tumour extent.

• Lymph node involvement.

• Liver metastases.

• Peritoneal disease.

Abdominal ultrasound scan

Useful for:

• Detection of abdominal metastases.

• Assessment of liver involvement.

Endoscopy and biopsy

Upper gastrointestinal endoscopy

Allows:

• Direct visualization of gastric lesions.

• Assessment of tumour location.

• Biopsy collection.

Histopathology

Confirms:

• Adenocarcinoma.

• Tumour differentiation.

• Histological subtype.

Staging

Gastric cancer is staged using the TNM staging system.

T – Primary tumour

Determined by:

• Depth of gastric wall invasion.

• Extension into adjacent organs.

N – Regional lymph nodes

Determined by:

• Number and location of involved lymph nodes.

M – Distant metastases

Assessment of spread to:

• Liver.

• Peritoneum.

• Lung.

• Other organs.

Staging determines treatment intent:

• Curative treatment.

• Disease control.

• Palliation.

Management

Management should follow a multidisciplinary approach based on:

• Tumour stage.

• Resectability.

• Histology.

• HER2 status.

• Patient fitness.

Management pathway:

1. Confirm diagnosis with endoscopy and biopsy.

2. Perform staging investigations.

3. Assess nutritional and functional status.

4. Provide definitive treatment where possible.

5. Provide palliative care for advanced disease.

Non-pharmacological treatment

Surgical treatment

Surgery remains the main curative treatment for localized gastric cancer.

Partial gastrectomy

Indicated for:

• Distal gastric tumours where adequate margins can be achieved.

Total gastrectomy

Indicated for:

• Proximal gastric cancers.

• Extensive disease involving most of the stomach.

Lymph node dissection

Performed together with gastrectomy for accurate staging and disease control.

Palliative surgery

Bypass surgery

Used to relieve:

• Gastric outlet obstruction.

• Inability to tolerate oral feeding.

Nutritional support

Management includes:

• Dietary counselling.

• Enteral feeding when required.

• Management of cancer-related malnutrition.

Radiotherapy

Radiotherapy may be used:

Adjuvant therapy

• After surgery with chemotherapy in selected patients.

Palliative therapy

Used for:

• Bleeding control.

• Pain relief.

• Symptom improvement.

Pharmacological treatment

Perioperative chemotherapy

Used before and after surgery in locally advanced resectable gastric cancer.

Regimen 1: ECF regimen

5-Fluorouracil (5-FU) – 500 mg/m² – intravenous bolus – day 1ANDEpirubicin – 50 mg/m² – intravenous infusion over 30 minutes – day 1ANDCisplatin – 60 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

Regimen 2

Capecitabine – 625 mg/m² – oral – every 12 hours – daily for 21 daysANDEpirubicin – 50 mg/m² – intravenous infusion over 30 minutes – day 1ANDCisplatin – 60 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

Regimen 3

5-Fluorouracil – 200 mg/m²/day – continuous intravenous infusion – day 1 to day 4ANDEpirubicin – 50 mg/m² – intravenous infusion over 30 minutes – day 1ANDCisplatin – 60 mg/m² – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

Treatment for locally advanced and metastatic gastric adenocarcinoma

Regimen 1

Paclitaxel – 175 mg/m² – intravenous infusion over 3 hours – day 1ANDCarboplatin – AUC 5 – intravenous infusion over 1 hour – day 1

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

HER2-positive disease

Add:

Trastuzumab – 6 mg/m² – intravenous infusion over 2 hours – loading dose day 1then:

Trastuzumab – 4 mg/m² – intravenous infusion – every 14 days

Regimen 2

Docetaxel – 60 mg/m² – intravenous infusion over 2 hours – day 1ANDCisplatin – 60 mg/m² – intravenous infusion over 1 hour – day 1AND5-Fluorouracil – 750 mg/m² – continuous intravenous infusion over 24 hours – day 1 to day 4

Frequency:

• Every 21 days.

Duration:

• 6 cycles.

For HER2-positive disease:

Add trastuzumab as above.

Palliative chemotherapy

Used for metastatic disease or patients unsuitable for curative treatment.

Capecitabine – 1000 mg/m² – oral – every 12 hours – day 1 to day 14

Frequency:

• Every 3 weeks.

Duration:

• 6 cycles or until:

  • Disease progression.

  • Intolerable toxicity.

Management according to underlying cause

Gastric adenocarcinoma

Management depends on stage:

Early-stage disease

• Surgical resection.

• Gastrectomy with lymph node dissection.

Locally advanced disease

• Perioperative chemotherapy.

• Surgery if resectable.

• Adjuvant chemoradiotherapy where indicated.

Metastatic disease

• Systemic chemotherapy.

• HER2-targeted therapy for HER2-positive tumours.

• Symptom-directed palliative care.

Gastric MALT lymphoma

Gastric MALT lymphoma is associated with chronic H. pylori infection.

Management includes:

1. H. pylori eradication therapy.

2. Chemotherapy or radiotherapy depending on disease extent.

Gastrointestinal stromal tumour (GIST)

Patients with:

• CD117-positive GIST

respond well to targeted therapy.

Treatment:

Imatinib – oral – dose according to tumour characteristics and oncology protocol

Used for:

• Advanced disease.

• Unresectable disease.

• High-risk disease.

Referral

All patients with suspected or confirmed gastric cancer should be referred to specialized cancer centres for multidisciplinary management.

Referral should involve:

• Surgical oncology.

• Medical oncology.

• Radiation oncology.

• Gastroenterology.

• Nutrition specialists.

Urgent referral indications

• Significant gastrointestinal bleeding.

• Gastric outlet obstruction.

• Severe weight loss.

• Malnutrition.

• Evidence of metastatic disease.

Complications

Disease-related complications

• Gastric outlet obstruction.

• Gastrointestinal bleeding.

• Severe malnutrition.

• Perforation (rare).

• Metastatic disease.

• Ascites due to peritoneal spread.

Treatment-related complications

Surgery

• Anastomotic leakage.

• Nutritional deficiencies.

• Infection.

Chemotherapy

• Myelosuppression.

• Nausea and vomiting.

• Renal toxicity from cisplatin.

• Cardiotoxicity from epirubicin.

Radiotherapy

• Gastritis.

• Fatigue.

• Local tissue injury.

Prognosis

Prognosis depends mainly on:

• Stage at diagnosis.

• Tumour histology.

• Lymph node involvement.

• Presence of metastases.

• Response to therapy.

• Patient nutritional status.

Early-stage gastric cancer treated surgically has better outcomes, whereas advanced metastatic disease has limited survival despite treatment.

Prevention

Preventive strategies include:

• Early detection and treatment of H. pylori infection.

• Avoid tobacco smoking.

• Reduce intake of smoked and salt-preserved foods.

• Increase consumption of fruits and vegetables.

• Maintain healthy body weight.

• Surveillance of high-risk individuals with hereditary gastric cancer syndromes.

• Early evaluation of persistent dyspepsia, weight loss, or gastrointestinal bleeding.