Gastric carcinoma refers to malignant neoplasms arising from the lining of the stomach, most commonly adenocarcinomas . It ranks among the leading causes of cancer-related deaths worldwide, often diagnosed at an advanced stage due to vague, non-specific symptoms.
Etiology and Risk Factors
Infectious
- Helicobacter pylori infection (strongly associated with intestinal-type gastric cancer)
- Epstein-Barr Virus (EBV) infection
Pre-malignant Conditions
- Chronic atrophic gastritis (especially autoimmune gastritis → pernicious anemia)
- Intestinal metaplasia
- Gastric adenomas
- Barrett's esophagus (though more commonly associated with esophageal adenocarcinoma)
Environmental & Lifestyle
- High intake of smoked, salted, pickled foods (nitrosamines)
- Cigarette smoking
- Alcohol consumption
- Low intake of fresh fruits and vegetables
Medical History
- Gastric ulcers (especially with H. pylori)
- Partial gastrectomy (bile reflux and remnant gastritis)
- History of radiation therapy to the upper abdomen
Genetic/Hereditary
- Familial Adenomatous Polyposis (FAP)
- Hereditary Diffuse Gastric Cancer (HDGC) – CDH1 mutation
- Lynch syndrome (HNPCC)
Clinical Features
Non-Specific Symptoms (Often described as 5 A’s) :
- Asthenia (weakness/fatigue)
- Abdominal pain (epigastric, retrosternal, or back; may mimic PUD)
- Anorexia with early satiety and nausea
- Anemia (due to chronic GI bleeding)
- Achlorhydria
Common Presentations
- Weight Loss – Most frequent presenting symptom
- Epigastric Pain – Worse postprandially; may be relieved by antacids
- Vomiting – Especially with tumors near the pylorus
- Dyspepsia, early satiety
- Gastrointestinal Bleeding – Hematemesis or melena (10%)
- Dysphagia – Suggests proximal (cardioesophageal junction) involvement
- Constipation – From poor intake
Signs Suggestive of Metastasis
| Feature | Implication |
|---|---|
| Jaundice | Hepatic or porta hepatis involvement |
| Virchow’s Node | Left supraclavicular LN metastasis |
| Sister Mary Joseph Nodule | Periumbilical nodule from peritoneal spread |
| Blumer's Shelf | Palpable rectal shelf (posterior cul-de-sac metastasis) |
| Krukenberg Tumor | Ovarian metastases (bilateral mucin-producing signet ring cells) |
| Acanthosis Nigricans | Paraneoplastic marker |
| Trousseau’s Sign | Migratory thrombophlebitis (more common in pancreatic CA) |
Physical Examination Findings
- Pallor (anemia)
- Cachexia, dehydration
- Palpable epigastric mass (advanced)
- Hepatomegaly (liver metastasis)
- Ascites (malignant)
- Lymphadenopathy (Virchow’s node, left supraclavicular)
- Umbilical nodule (Sister Mary Joseph)
- Pelvic shelf on DRE (Blumer’s shelf)
Diagnostic Evaluation
First-Line Investigation
- Esophagogastroduodenoscopy (EGD) with biopsy and brush cytology
- Gold standard
- ≥6 biopsies from suspicious lesions
Imaging
| Test | Use |
|---|---|
| Barium meal (double contrast) | Alternative if endoscopy not available |
| Endoscopic Ultrasound (EUS) | Best for assessing tumor invasion depth & nodal spread |
| CT scan (abdomen & pelvis) | Staging, assess resectability, detect metastases |
| PET-CT | Whole-body staging; useful for detecting occult metastases |
| Abdominal Ultrasound | Evaluate liver metastases, ascites, Krukenberg tumor |
| Chest X-ray | Pulmonary metastasis assessment |
| Laparoscopy | Detect peritoneal seeding, operability, cytology washout |
Laboratory Tests
- CBC – Microcytic anemia from chronic blood loss
- Liver Function Tests (LFTs) – Elevated bilirubin, ALP if liver metastasis
- CEA (Carcinoembryonic Antigen) – Elevated in advanced disease, useful for follow-up
- Stool occult blood test – Often positive
Staging – TNM (AJCC 8th Edition)
T – Tumor Invasion
- Tis – Carcinoma in situ
- T1 – Submucosa
- T2 – Muscularis propria
- T3 – Subserosa
- T4a – Serosa
- T4b – Adjacent organs (e.g., pancreas, colon, liver)
N – Regional Lymph Nodes
- N0 – No lymph node involvement
- N1 – 1–2 nodes
- N2 – 3–6 nodes
- N3 – ≥7 nodes
M – Distant Metastasis
- M0 – No distant spread
- M1 – Metastasis present (e.g., liver, peritoneum, lungs)
Principles of Management
- Management depends on tumor stage , location , histology , patient performance status , and metastatic spread .
- Multidisciplinary approach : Surgery, oncology, gastroenterology, radiology, and palliative care.
Curative Treatment (Localized/Resectable Disease)
Surgical Resection – Mainstay of Treatment
Type of Surgery
| Location of Tumor | Procedure |
|---|---|
| Distal stomach | Subtotal (distal) gastrectomy |
| Proximal or diffuse tumor | Total gastrectomy |
| Tumor extends to adjacent organs | En bloc resection |
Surgery includes D2 lymphadenectomy (removal of perigastric + regional nodes). D1 alone is insufficient for curative intent.
Neoadjuvant Therapy (Pre-operative Chemotherapy)
- Indicated for stage ≥ IB (T2+ or N+) disease
- Improves survival and resectability
- Example regimen:
FLOT = 5-FU + Leucovorin + Oxaliplatin + Docetaxel
Adjuvant Therapy (Post-operative)
- Given after surgery to reduce recurrence
- Options:
- Chemoradiotherapy (e.g., 5-FU + radiation)
- Adjuvant chemotherapy alone (especially in Asia – S-1 based)
Unresectable/Advanced/Metastatic Gastric Cancer
Palliative Care Goals
- Alleviate symptoms
- Prolong survival
- Maintain quality of life
Palliative Interventions
| Symptom | Intervention |
|---|---|
| Gastric outlet obstruction | Endoscopic stent / Gastrojejunostomy |
| Bleeding tumor | Endoscopic hemostasis / Radiotherapy |
| Pain, nausea | Opioids, antiemetics |
| Ascites | Paracentesis, diuretics |
| Obstructive jaundice | Biliary stenting |
Systemic Chemotherapy
- Extends survival in metastatic disease
- Common regimens:
- FOLFOX : 5-FU + leucovorin + oxaliplatin
- EOX : Epirubicin + Oxaliplatin + Capecitabine
- FLOT
- HER2-positive tumors: Add trastuzumab (HER2-targeted therapy)
- MSI-H/dMMR tumors: Respond to immune checkpoint inhibitors (e.g., pembrolizumab)
Targeted & Immunotherapy (Advanced Disease)
| Target | Drug | Indication |
|---|---|---|
| HER2 | Trastuzumab | HER2+ gastric adenocarcinoma |
| VEGF | Ramucirumab | 2nd-line for advanced disease |
| PD-1 | Nivolumab / Pembrolizumab | MSI-H or PD-L1+ tumors |
Surveillance Post-Treatment
- Regular physical exams, labs, imaging (CT)
- Frequency: every 3–6 months for 2 years, then annually
- Monitor for recurrence, nutritional status (especially post-gastrectomy)
Nutritional Support
- Small frequent meals, high protein and calorie intake
- Vitamin B12 supplementation (if total gastrectomy)
- Monitor for dumping syndrome
- Dietician referral is essential
Prognosis
- Prognosis depends on stage:
- Localized: 5-year survival ~70%
- Regional spread: ~30–50%
- Metastatic: <10%
- Early detection dramatically improves outcomes
High-Yield Clinical Pearls
| Concept | Key Point |
|---|---|
| Most curable subtype | Intestinal-type (especially early-stage) |
| Best for early-stage detection | Japan/Korea use mass endoscopic screening |
| MSI-H tumors | Good response to immunotherapy |
| Most important prognostic factor | Stage at diagnosis |
| Recurrence monitoring | CEA & imaging |
| Common recurrence | Peritoneal carcinomatosis |
