Prostate
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Etiology & Risk Factors
Stomach cancer is a multifactorial disease, with over 90% of cases being adenocarcinomas. The etiology is generally divided into environmental triggers and genetic predispositions.
Environmental & Lifestyle Triggers
- Infectious Agents: Helicobacter pylori remains the primary risk factor, causing chronic atrophic gastritis and intestinal metaplasia. Epstein-Barr Virus (EBV) is associated with approximately 10% of cases, often exhibiting a distinct immune-rich phenotype.
- Dietary Factors: High intake of salted, smoked, or nitrate-preserved foods; low intake of fresh fruits and vegetables.
- Lifestyle: Tobacco smoking (increases risk by ~60%) and heavy alcohol consumption.
- Obesity: Strongly linked to Gastric Cardia and Gastroesophageal Junction (GEJ) cancers.
Genetic & Familial Predisposition
- Hereditary Diffuse Gastric Cancer (HDGC): Driven by germline mutations in the CDH1 gene (encoding E-cadherin). Prophylactic total gastrectomy is often indicated for carriers.
- Lynch Syndrome: Germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2).
- Other Syndromes: Familial Adenomatous Polyposis (FAP), Li-Fraumeni Syndrome (TP53), and BRCA1/BRCA2 mutations.
Clinical Manifestations (Symptoms)
Symptoms are often insidious, leading to frequent late-stage diagnoses.
Early-Stage Symptoms
- Vague dyspepsia (indigestion) or epigastric discomfort.
- Early satiety (feeling full quickly).
- Occult gastrointestinal bleeding leading to iron-deficiency anemia.
Advanced-Stage Symptoms
- Unintentional weight loss and anorexia.
- Dysphagia: Common in cardia/GEJ tumors.
- Nausea/Vomiting: Persistent vomiting may indicate gastric outlet obstruction.
- Physical Signs of Metastasis:
- Virchow’s Node: Left supraclavicular lymphadenopathy.
- Sister Mary Joseph Nodule: Periumbilical metastasis.
- Blumer’s Shelf: Palpable mass in the rectovesical or rectouterine pouch.
Paraneoplastic Syndromes
- Trousseau Syndrome: Migratory thrombophlebitis.
- Leser-Trélat Sign: Sudden onset of multiple seborrheic keratoses.
- Acanthosis Nigricans: Hyperpigmented, velvety skin patches (axilla/neck).
- Paraneoplastic Polyarthritis: Rare, symmetric arthritis that precedes diagnosis.
Diagnostic Workup
The “Gold Standard” is Upper Endoscopy (EGD) with multiple biopsies (at least 6-8 samples for adequate yield).
Biomarker Testing
Upon diagnosis of advanced disease, universal testing for the following is mandatory:
- HER2/neu: Standard IHC/ISH testing.
- PD-L1 Expression: Measured via Combined Positive Score (CPS).
- MSI/MMR Status: To identify candidates for immunotherapy.
- CLDN18.2 (Claudin 18.2): Now a critical biomarker for HER2-negative patients.
Investigations & Staging
Imaging Modalities
- CT Chest/Abdomen/Pelvis (with oral/IV contrast): Initial tool for staging and detecting visceral metastases.
- Endoscopic Ultrasound (EUS): The most accurate modality for T (depth of invasion) and N (regional node) staging.
- PET-CT: Used to detect occult distant metastases (M-stage) not seen on CT, though less sensitive for diffuse-type or mucinous tumors.
- Diagnostic Laparoscopy: Recommended for all tumors to rule out radiographically occult peritoneal carcinomatosis.
Treatment Overview
A multidisciplinary team (MDT) approach is required.
Surgery
- Standard: Radical Gastrectomy (Total or Subtotal) with D2 Lymphadenectomy.
- Minimal Invasive Surgery (MIS): Robotic or laparoscopic-assisted gastrectomy is now common for early and select locally advanced cases, offering faster recovery.
Radiotherapy
- Techniques: IMRT (Intensity-Modulated Radiation Therapy) is the standard to minimize dose to the heart, liver, and kidneys.
- Role: Primarily used as adjuvant therapy in patients with suboptimal (D0/D1) lymph node dissection or as palliative therapy for bleeding/obstruction.
Systemic Therapy
- Perioperative (FLOT Regimen): 5-FU, Leucovorin, Oxaliplatin, and Docetaxel is the preferred standard.
- Immunotherapy:
- Nivolumab: Combined with chemotherapy for PD-L1 CPS ≥5 (1st line).
- Durvalumab: Recently integrated into perioperative protocols (e.g., MATTERHORN trial).
- Targeted Therapy:
- Zolbetuximab (Vyloy): A first-in-class antibody targeting CLDN18.2, used in combination with chemotherapy for CLDN18.2-positive/HER2-negative advanced disease.
- Trastuzumab Deruxtecan (T-DXd): Standard for HER2-positive patients in later lines of therapy.
Emerging Therapies
- Zanidatamab: A bispecific antibody targeting two distinct HER2 epitopes, showing high efficacy in HER2-amplified GEJ cancers.
- CLDN18.2 CAR-T Therapy: Early-phase trials are showing promising responses in refractory gastric adenocarcinoma.
- Antibody-Drug Conjugates (ADCs): Novel agents like Disitamab Vedotin are expanding treatment options for "HER2-low" populations.
Medical Disclaimer
This document is intended for healthcare professionals for informational purposes only.
It does not constitute medical advice, diagnosis, or treatment.
Treatment decisions should be made by qualified oncologists based on individual patient factors and the most recent NCCN or local guidelines.
Always verify drug dosages and indications against official prescribing information.