Gastric Cancer Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: This is one of the top 10 most common cancers in Malaysian men. The key problem is late presentation; the majority of our patients present with advanced, incurable disease, leading to a high mortality-to-incidence ratio.
High-Yield Definition: Gastric adenocarcinoma is a malignancy arising from the epithelial cells of the stomach lining. Over 90% of stomach cancers are adenocarcinomas.
Clinical One-Liner: Basically, it's a cancer of the stomach lining that patients ignore as "gastric" for too long, often driven by H. pylori infection.
II. Etiology & Risk Factors
Etiology: Primarily caused by chronic inflammation leading to sequential mucosal changes (the Correa cascade), most commonly initiated by chronic Helicobacter pylori infection. Epstein-Barr virus (EBV) is another, less common, infectious trigger.
Risk Factors:
Non-modifiable:
Ethnicity: This is crucial in Malaysia. Incidence is significantly higher in Chinese and Indians compared to Malays.
Age: Risk increases sharply after 50 years old.
Gender: Male > Female (~2:1).
Genetic: Family history of gastric cancer, hereditary syndromes (e.g., Lynch syndrome, Hereditary Diffuse Gastric Cancer - CDH1 mutation).
Modifiable:
Helicobacter pylori infection: The single most important risk factor.
Diet: High intake of salted, smoked, or pickled foods. Low intake of fresh fruits and vegetables.
Smoking: Established risk factor.
Alcohol: Heavy consumption.
Previous Gastric Conditions: Chronic atrophic gastritis, pernicious anaemia, previous partial gastrectomy.
III. Quick Pathophysiology
Think of it as a step-ladder process, known as the Correa cascade. It starts with chronic inflammation from an insult like H. pylori. This leads to atrophic gastritis (loss of normal gastric glands), which is then replaced by intestinal metaplasia (stomach lining starts to look like intestinal lining). This metaplastic tissue can then become dysplastic, which is the final pre-cancerous step before it progresses to invasive adenocarcinoma. This entire process can take years.
IV. Clinical Assessment
Red Flags & Immediate Actions:
New-onset dysphagia: Urgent OGDS referral within 2 weeks.
Persistent vomiting / Signs of gastric outlet obstruction: Keep patient nil by mouth (NBM), insert a Ryle's tube on free drainage, start IV drips, and alert your senior/surgical team.
Melaena / Haematemesis: Secure two large bore IV cannulae, send FBC and Group & Crossmatch (GXM), start IV pantoprazole, and escalate immediately for an emergency endoscopy.
Unexplained weight loss >10% or palpable epigastric mass: Warrants urgent investigation; present the case in the next ward round for an OGDS slot.
History:
Common (>50%): Often asymptomatic in early stages. Vague epigastric pain, persistent dyspepsia not responding to standard treatment, early satiety.
Less Common (10-50%): Nausea, anorexia, heartburn.
Rare (<10%, but indicates advanced disease): Frank symptoms from complications - dysphagia (GOJ involvement), vomiting (outlet obstruction), melaena/haematemesis (bleeding tumour).
Physical Examination:
Often unremarkable in early disease.
Key signs of advanced disease:
General: Cachexia, pallor (from anaemia).
Abdomen: Palpable epigastric mass, hepatomegaly (metastases), ascites.
Metastatic Signs:
Virchow's node: Left supraclavicular lymphadenopathy.
Sister Mary Joseph nodule: Umbilical nodule.
Krukenberg tumour: Ovarian metastases (may be found on PR exam as a pelvic mass).
Acanthosis nigricans: Paraneoplastic sign.
Clinical Pearl: Have a very low threshold to scope middle-aged (40+) Chinese and Indian patients presenting with new-onset dyspepsia, especially if associated with any alarm features. Don't just treat them with endless PPIs.
V. Diagnostic Workflow
Differential Diagnosis:
Peptic Ulcer Disease (PUD):
Points For: Epigastric pain, history of NSAID use or H. pylori.
Points Against: Malignant ulcers often have heaped-up, irregular edges.
How to Differentiate: Endoscopy with biopsy is mandatory. All gastric ulcers must be biopsied and re-scoped to ensure healing, as they can be malignant.
Gastroesophageal Reflux Disease (GORD):
Points For: Heartburn, regurgitation, worse on lying flat.
Points Against: Systemic symptoms like weight loss are absent.
How to Differentiate: Response to PPI is usually good. Endoscopy if alarm features are present.
Functional Dyspepsia:
Points For: Chronic dyspeptic symptoms with no identifiable organic cause.
Points Against: A diagnosis of exclusion. Red flags must be absent.
How to Differentiate: Normal endoscopy.
Investigations Plan:
Bedside / Initial:
Vital signs: Check for tachycardia/hypotension in bleeding patients.
First-Line Labs & Imaging:
FBC: To detect anaemia from chronic or acute bleeding.
Renal profile, LFTs, Albumin: Baseline for chemotherapy fitness and to check for liver metastases or malnutrition.
Tumour markers (CEA, CA19-9): Not for diagnosis. Used as a baseline to monitor treatment response in advanced disease if initially elevated.
Confirmatory / Gold Standard:
Oesophagogastroduodenoscopy (OGDS) with Biopsy: This is the definitive diagnostic test. Multiple biopsies (at least 5-8 as per Pan-Asian ESMO guidelines) should be taken from the ulcer edge and base.
Staging CT Scan: Contrast-enhanced CT of the Thorax, Abdomen, and Pelvis is mandatory to stage the disease (assess tumour extent, nodal involvement, and distant metastases) once cancer is confirmed.
Staging Laparoscopy: May be considered in potentially resectable cases to rule out small peritoneal metastases not visible on CT.
VI. Staging & Severity Assessment
We use two key systems to classify and stage the cancer, which dictates our entire management plan.
1. Lauren Histological Classification:
Intestinal Type: Forms glandular structures. More common in older males, associated with environmental factors (H. pylori, diet), often arises from intestinal metaplasia, and carries a slightly better prognosis.
Diffuse Type: Poorly cohesive cells, no glands, often with "signet-ring" cells. Tends to affect younger patients (including women), has a stronger genetic link, infiltrates the stomach wall extensively (linitis plastica), and carries a worse prognosis.
2. TNM Staging (AJCC 8th Edition):
T (Tumour): Describes the depth of tumour invasion through the stomach wall (T1=submucosa, T2=muscularis propria, T3=subserosa, T4=invades serosa or adjacent structures).
N (Nodes): Describes the number of regional lymph nodes involved (N0=none, N1=1-2, N2=3-6, N3=7+).
M (Metastasis): Presence of distant spread (M0=no, M1=yes).
Impact: These are combined to give a stage from I (early) to IV (metastatic). Stage I-III is potentially curable. Stage IV is treated with palliative intent.
VII. Management Plan
Management is decided in a multidisciplinary team (MDT) meeting with surgeons, oncologists, and radiologists. The approach depends entirely on the stage.
Immediate Stabilisation (The ABCDE Plan):
This is for acute presentations like bleeding or obstruction.
Airway, Breathing, Circulation: Resuscitate as needed. Give IV fluids, transfuse blood if haemodynamically unstable (aim Hb > 7-8 g/dL).
IV Pantoprazole 80mg bolus then 8mg/hr infusion for active bleeding.
Keep NBM and insert NGT for gastric outlet obstruction.
Definitive Treatment (The Ward Round Plan):
Localised Disease (Stage I-III - Curative Intent):
Perioperative Chemotherapy: The standard of care for T2 or node-positive disease. Usually the FLOT regimen (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel) given before and after surgery. This improves survival compared to surgery alone.
Surgery: Radical gastrectomy (subtotal or total, depending on location) with a D2 lymphadenectomy (removal of specified lymph node stations). This is a major operation.
Advanced/Metastatic Disease (Stage IV - Palliative Intent):
The goal is to prolong survival and maintain quality of life.
First-Line Systemic Therapy: Combination chemotherapy, typically a platinum (Oxaliplatin) and a fluoropyrimidine (Capecitabine or 5-FU).
Biomarker-Guided Therapy: Before starting treatment, the biopsy sample must be tested for:
HER2: If positive (amplified), Trastuzumab (a targeted antibody) is added to chemotherapy.
PD-L1 (CPS score): If CPS ≥ 5, Nivolumab (an immunotherapy agent) is added to chemotherapy.
MSI status: If MSI-High, immunotherapy may be an option.
Second-Line & Beyond: Options include Ramucirumab, Paclitaxel, or Irinotecan depending on patient fitness and previous treatments.
Long-Term & Discharge Plan:
Nutritional support: Crucial post-gastrectomy. Involve the dietitian. Patients need small, frequent meals and may need supplements (Iron, B12, Calcium, Vitamin D).
Surveillance: Follow-up in clinic. Surveillance endoscopy may be planned.
Palliative Care: Early referral for patients with advanced disease is essential for symptom control.
VIII. Complications
Immediate (Disease-related):
Upper GI Bleeding: Management: Resuscitate, IV PPI, urgent OGDS for haemostasis.
Gastric Outlet Obstruction: Management: NGT decompression, IV fluids. May require surgical bypass or endoscopic stenting.
Perforation: Management: Surgical emergency requiring laparotomy and repair/resection.
Short-Term (Treatment-related):
Anastomotic Leak: Management: A major surgical complication requiring re-operation or conservative management with drains and antibiotics.
Post-gastrectomy Dumping Syndrome: Management: Dietary modification (small, low-carb meals), advice from dietitian.
Long-Term (Treatment-related):
Malnutrition & Vitamin Deficiencies: Management: Lifelong monitoring and supplementation (B12 injections, oral iron/calcium).
Recurrence: Management: Palliative systemic therapy.
IX. Prognosis
The prognosis is highly dependent on the stage at diagnosis.
In Malaysia, the prognosis is generally poor due to late presentation. The mortality-to-incidence ratio is high.
5-Year Overall Survival:
Stage I: >70-80%
Stage II-III: 30-50% (with perioperative chemo + surgery)
Stage IV: <5%
Key Prognostic Factors: Stage (especially lymph node status - 'N' stage), Lauren classification (diffuse is worse), and achieving a complete surgical resection (R0).
X. How to Present to Your Senior
Use the SBAR format. Be concise.
"Dr., for review please. This is Mr. Lim in Bed 10, a 65-year-old Chinese man with a history of dyspepsia, who presented with a one-month history of anorexia and 5kg weight loss.
On examination, he is pale and there is mild epigastric tenderness. His haemoglobin is 9.1.
My main differential is gastric malignancy.
I have already sent off his FBC and renal profile. I would like to request an urgent OGDS for him. Can we get him on the list for tomorrow?"
XI. Summary & Further Reading
Top 3 Takeaways:
Have a high index of suspicion for gastric cancer in older Chinese/Indian patients with new-onset dyspepsia and alarm symptoms.
The definitive diagnosis is by OGDS and multiple biopsies. Staging is with a CT scan.
Management is stage-dependent: perioperative chemotherapy and surgery for curative intent vs. palliative chemotherapy ± targeted/immunotherapy for metastatic disease.
Key Resources:
Primary Guideline: Pan-Asian adapted ESMO Clinical Practice Guidelines for... gastric cancer (2023) - This is the key consensus statement involving Malaysian experts.
Local Context: A Review of Gastric Cancer Research in Malaysia (2019)
International Reference: UpToDate - Search for "Clinical features, diagnosis, and staging of gastric cancer".
