Gastric cancer Medical Services in China

Gastric cancer, also known as stomach cancer, is a malignant neoplasm arising from the epithelial lining of the gastric mucosa—most commonly adenocarcinoma (accounting for over 90% of cases). It typically develops through a multistep carcinogenic cascade: chronic gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → invasive adenocarcinoma. This progression is strongly associated with persistent Helicobacter pylori infection, which induces chronic inflammation, oxidative DNA damage, and aberrant cell proliferation. Other pathogenic mechanisms include Epstein-Barr virus (EBV) integration in ~10% of cases, microsatellite instability (MSI-H), and CDH1 germline mutations in hereditary diffuse gastric cancer (HDGC). Globally, gastric cancer ranks fifth in incidence and fourth in cancer-related mortality, with an estimated 969,000 new cases and 738,000 deaths annually (GLOBOCAN 2022). Incidence is markedly higher in East Asia (especially Korea, Japan, and China), Eastern Europe, and parts of Central and South America—regions where high-salt diets, smoked/preserved foods, smoking, and widespread H. pylori prevalence converge. In China alone, gastric cancer accounts for approximately 40% of global cases, with age-standardized incidence rates exceeding 25 per 100,000 in high-risk provinces. Key modifiable risk factors include long-standing H. pylori infection (relative risk ~3–6), tobacco use (2-fold increased risk), excessive salt intake, low fruit/vegetable consumption, and heavy alcohol consumption. Non-modifiable risks include male sex (2:1 male-to-female ratio), advanced age (median diagnosis at 68 years), family history, blood type A, and genetic syndromes such as Lynch syndrome or HDGC. Early-stage disease is often asymptomatic; later symptoms—including persistent epigastric pain, early satiety, unintentional weight loss, nausea, vomiting (sometimes with hematemesis), and iron-deficiency anemia—frequently indicate locally advanced or metastatic disease. Diagnosis relies on upper gastrointestinal endoscopy with systematic biopsy, enhanced by chromoendoscopy or magnification techniques in high-prevalence regions. Staging integrates EUS, contrast-enhanced CT, and sometimes PET-CT or diagnostic laparoscopy. Quality of life is profoundly impacted: patients experience significant nutritional compromise due to impaired gastric digestion and motility, fatigue from chronic inflammation and anemia, anxiety related to prognosis (5-year survival drops from >70% in Stage I to <10% in Stage IV), and psychosocial burden affecting work capacity, social engagement, and caregiver dynamics. Palliative care integration—addressing pain, nausea, depression, and nutritional support—is essential across all stages to preserve dignity and functional independence.

Gastric cancer, or gastric adenocarcinoma, is a heterogeneous malignancy arising from the glandular epithelium of the stomach mucosa. Its pathogenesis involves a multistep cascade—often described by the Correa model—progressing from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and ultimately invasive carcinoma. While no single cause accounts for all cases, gastric cancer results from complex interactions among infectious agents, host genetics, environmental exposures, and lifestyle factors.

The most well-established causative agent is chronic infection with Helicobacter pylori (H. pylori), present in over 90% of non-cardia gastric cancers. H. pylori induces persistent inflammation, oxidative DNA damage, and disruption of gastric epithelial cell turnover. Strains expressing the cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) confer higher oncogenic risk due to enhanced pro-inflammatory signaling and epithelial barrier dysfunction. Eradication of H. pylori significantly reduces gastric cancer incidence, particularly when performed before the onset of preneoplastic changes.

Dietary factors serve as major modifiable triggers and risk amplifiers. High intake of salted, smoked, pickled, or nitrate-preserved foods promotes gastric mucosal injury and endogenous nitrosamine formation—potent carcinogens that alkylate DNA. Conversely, diets deficient in fresh fruits and vegetables—sources of antioxidants (e.g., vitamin C, selenium, beta-carotene) and dietary fiber—are associated with elevated risk. Smoking tobacco doubles the risk of gastric adenocarcinoma, likely through direct mucosal toxicity, systemic inflammation, and impaired DNA repair. Heavy alcohol consumption, though less consistently linked than in hepatocellular or esophageal cancers, contributes synergistically with H. pylori and smoking.

Genetic susceptibility plays a critical role in a subset of cases. Hereditary diffuse gastric cancer (HDGC) syndrome, caused by germline pathogenic variants in CDH1 (encoding E-cadherin), confers up to 70–80% lifetime risk of diffuse-type gastric cancer and mandates prophylactic gastrectomy in confirmed carriers. Other hereditary syndromes include Lynch syndrome (mismatch repair gene mutations—MLH1, MSH2, MSH6, PMS2, EPCAM), which increases risk for intestinal-type gastric cancer; familial adenomatous polyposis (APC gene); and Li-Fraumeni syndrome (TP53). Genome-wide association studies have identified common low-penetrance polymorphisms in genes involved in inflammation (e.g., IL-1β, TNF-α), H. pylori response (TLR4), and folate metabolism (MTHFR), further underscoring host genetic modulation of risk.

Environmental and socioeconomic determinants are strongly implicated. Gastric cancer incidence is markedly higher in East Asia (Japan, Korea, China), Eastern Europe, and Central and South America—regions where H. pylori prevalence is high and traditional diets are salt- and nitrite-rich. Lower socioeconomic status correlates with increased risk, likely reflecting earlier H. pylori acquisition, limited access to refrigeration (leading to reliance on salted/preserved foods), and reduced healthcare utilization for early detection and eradication therapy. Occupational exposures—including dusts and fumes in coal mining, metal processing, and rubber manufacturing—have been associated with modestly elevated risks, possibly via chronic irritation or co-carcinogenic effects.

Additional clinical risk factors include pernicious anemia (autoimmune atrophic gastritis with achlorhydria and intrinsic factor deficiency), prior gastric surgery (e.g., Billroth II resection >15 years prior, associated with bile reflux and bacterial overgrowth), and Epstein-Barr virus (EBV)-positive gastric carcinoma (found in ~10% of cases, typically proximal or remnant stomach tumors with distinct molecular features including PD-L1 upregulation and PIK3CA mutations). Chronic use of proton pump inhibitors (PPIs) remains controversial; while long-term acid suppression may promote gastric atrophy in H. pylori-positive individuals, current evidence does not support PPIs as independent carcinogens.

In summary, gastric cancer arises from cumulative insults: microbial (H. pylori), dietary (high salt, low antioxidants), behavioral (smoking), genetic (CDH1, MMR genes), and environmental (socioeconomic, occupational). Prevention strategies emphasize H. pylori screening/eradication in high-risk populations, dietary modification, smoking cessation, and targeted genetic counseling for families with hereditary syndromes.

Gastric cancer—also known as stomach cancer—is a malignant neoplasm arising from the gastric mucosa, most commonly of adenocarcinoma histology (accounting for >90% of cases). It remains a leading cause of cancer-related mortality worldwide, particularly in East Asia, Eastern Europe, and parts of South America. Due to its anatomical location and insidious progression, gastric cancer often remains asymptomatic or presents with nonspecific, easily overlooked manifestations in early stages, contributing to delayed diagnosis and poorer prognosis. Understanding the symptomatology across disease phases is critical for timely recognition and intervention by gastroenterologists.

Early symptoms are frequently subtle, intermittent, and indistinguishable from benign gastrointestinal disorders. Patients may report mild, persistent epigastric discomfort or a vague sense of fullness after eating small amounts (early satiety), which is often attributed to functional dyspepsia or gastritis. Other early indicators include unexplained anorexia, subtle weight loss (<5% body weight over 3–6 months), and occasional nausea without vomiting. Some individuals experience mild, intermittent postprandial bloating or belching. Importantly, early-stage gastric cancer—particularly lesions confined to the mucosa or submucosa (T1a/T1b)—may be entirely asymptomatic and detected only incidentally during upper endoscopy performed for unrelated indications (e.g., screening in high-risk populations or evaluation of iron-deficiency anemia).

As the tumor advances locally (T2–T4) or metastasizes, typical symptoms become more pronounced and persistent. Progressive epigastric pain—often described as dull, burning, or gnawing—is reported by approximately 60–75% of patients at diagnosis; unlike peptic ulcer disease, this pain typically does not correlate with meals and shows poor response to proton pump inhibitors or antacids. Hematemesis (vomiting blood) or melena (black, tarry stools) occurs in 15–30% of cases and reflects tumor-associated mucosal erosion or ulceration. Occult gastrointestinal bleeding may manifest solely as iron-deficiency anemia, evidenced by fatigue, pallor, exertional dyspnea, and reduced exercise tolerance—often the first laboratory clue in otherwise asymptomatic individuals. Progressive dysphagia suggests proximal (cardiac or fundal) tumor extension into the gastroesophageal junction, while persistent nausea and recurrent non-bilious vomiting indicate distal gastric outlet obstruction, especially when associated with visible gastric peristalsis or succussion splash on physical exam.

Accompanying symptoms reflect systemic inflammation, metabolic derangement, or paraneoplastic phenomena. Significant unintentional weight loss (>10% body weight over 6 months) is present in >65% of advanced cases and correlates with tumor burden and cachexia—a multifactorial syndrome driven by cytokine-mediated catabolism (e.g., TNF-α, IL-6, IFN-γ). Fatigue is nearly universal in advanced disease and results from anemia, malnutrition, chronic inflammation, and tumor-derived factors. Anorexia is frequently profound and precedes measurable weight loss. Less common but clinically significant accompanying features include new-onset thromboembolic events (e.g., deep vein thrombosis or migratory superficial thrombophlebitis—Trousseau’s sign), acanthosis nigricans (velvety hyperpigmented skin folds), or paraneoplastic dermatomyositis—each warranting urgent oncologic evaluation. Patients may also develop hypoalbuminemia-related peripheral edema or ascites secondary to portal vein invasion or peritoneal carcinomatosis.

Complications arise from local invasion, metastatic spread, or treatment-related sequelae. Gastrointestinal hemorrhage can progress to hemodynamic instability or require transfusion. Gastric outlet obstruction leads to gastric retention, electrolyte imbalances (hypokalemia, hypochloremic metabolic alkalosis), and nutritional depletion. Perforation—though rare (<2%)—presents acutely with severe abdominal pain, rigidity, and signs of peritonitis. Direct invasion into adjacent structures may cause pancreatitis (via pancreatic head infiltration), jaundice (due to common bile duct compression), or left supraclavicular lymphadenopathy (Virchow’s node), indicating nodal metastasis. Peritoneal carcinomatosis commonly causes malignant ascites, bowel obstruction, and diffuse abdominal pain. Hepatic metastases may result in right upper quadrant pain, hepatomegaly, or coagulopathy. Distant metastases to lungs (cough, hemoptysis, dyspnea), bone (pathologic fractures, hypercalcemia), or brain (headache, focal neurologic deficits) occur in late-stage disease.

Diagnosis relies on a multimodal approach. Upper gastrointestinal endoscopy with systematic biopsy remains the gold standard: high-definition white-light endoscopy supplemented by chromoendoscopy (indigo carmine or acetic acid) or image-enhanced techniques (narrow-band imaging, linked-color imaging) improves detection of flat or depressed early lesions. At least six biopsies should be obtained from suspicious areas—including the ulcer margin and base—to maximize diagnostic yield. Endoscopic ultrasound (EUS) is indispensable for locoregional staging: it accurately differentiates T1–T2 (confined to gastric wall) from T3–T4 (transmural invasion) and assesses regional lymph node involvement (N staging) with ~80–85% sensitivity. Contrast-enhanced CT of the chest, abdomen, and pelvis evaluates distant metastases (M staging), including liver, lung, adrenal, and peritoneal deposits. PET-CT adds value in detecting occult nodal or extraregional disease but has limited utility for mucosal-only lesions due to low FDG avidity. Serum biomarkers—including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9)—lack sensitivity for early detection but may aid in monitoring treatment response or recurrence.

Differential diagnosis must exclude both benign and malignant mimics. Functional dyspepsia, chronic gastritis (especially autoimmune or H. pylori-associated), peptic ulcer disease, and gastric lymphoma (MALT lymphoma) commonly present with overlapping symptoms such as epigastric pain, early satiety, and anemia. Gastric lymphoma may demonstrate endoscopic features resembling adenocarcinoma (ulceration, mass), necessitating deeper biopsies and immunohistochemistry. Gastroesophageal reflux disease (GERD) and eosinophilic gastroenteritis can mimic early satiety and nausea. Benign gastric polyps (hyperplastic, fundic gland) rarely cause symptoms unless large or pedunculated. Metastatic disease to the stomach (e.g., from breast or melanoma) is exceedingly rare but must be considered in patients with known primary malignancy. Non-gastric causes of iron-deficiency anemia—including celiac disease, colonic neoplasms, or menorrhagia—require exclusion, particularly in younger patients without classic risk factors (e.g., age >50, family history, chronic atrophic gastritis, pernicious anemia, or prior gastric surgery). Ultimately, definitive diagnosis rests on histopathological confirmation via endoscopic biopsy, with molecular profiling (e.g., HER2 immunohistochemistry/FISH, MSI/MMR testing, PD-L1 expression) increasingly guiding targeted and immunotherapeutic strategies.

Gastric cancer—also known as stomach cancer—is a malignant neoplasm arising from the gastric mucosa, most commonly adenocarcinoma. Its management requires a multidisciplinary approach integrating endoscopic evaluation, histopathological staging, molecular profiling, and individualized therapeutic planning. Treatment strategies are stratified by tumor stage (per AJCC/UICC TNM 8th edition), patient performance status, comorbidities, and biomarker status (e.g., HER2, PD-L1, MSI-H/dMMR). In the Department of Gastroenterology, initial diagnosis and conservative management—including surveillance, chemoprevention, and symptom control—are central to early-stage and unresectable or metastatic disease.

Conservative treatment is indicated for patients with early gastric cancer (T1a or select T1b lesions) without lymphovascular invasion, those unfit for surgery due to advanced age or severe comorbidities, or those with widespread metastatic disease where palliation supersedes curative intent. Endoscopic resection—specifically endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)—is the cornerstone of minimally invasive curative therapy for intramucosal (T1a) and superficial submucosal (T1b SM1, ≤500 µm invasion) cancers meeting strict criteria (e.g., well-to-moderately differentiated, <2 cm, no ulceration). ESD achieves higher en bloc and R0 resection rates (>90%) compared to EMR and is widely adopted in high-volume centers across China. For unresectable locally advanced or metastatic disease, conservative management focuses on nutritional optimization (including enteral feeding support when gastroparesis or obstruction occurs), antiemetic regimens (e.g., 5-HT3 antagonists + NK1 receptor antagonists), proton pump inhibitors for acid-related symptoms, and opioid-based analgesia for pain control. Psychosocial support and palliative care integration are initiated early to improve quality of life.

Pharmacotherapy plays a pivotal role across disease stages. Adjuvant chemotherapy—typically capecitabine/oxaliplatin (XELOX) or S-1 monotherapy—is standard after D2 gastrectomy for stage II–III disease, improving 5-year overall survival by 10–15% versus surgery alone. Neoadjuvant chemotherapy (e.g., FLOT regimen: 5-FU, leucovorin, oxaliplatin, docetaxel) is increasingly used for locally advanced resectable tumors (cT3–4/N+), enhancing R0 resection rates and downstaging. For HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, trastuzumab combined with platinum-fluoropyrimidine chemotherapy remains first-line; newer agents such as trastuzumab deruxtecan show promising activity in pretreated patients. Immune checkpoint inhibitors have transformed systemic therapy: nivolumab plus chemotherapy is approved for first-line advanced gastric/GEJ cancer regardless of PD-L1 status, while pembrolizumab is indicated for MSI-H/dMMR or PD-L1–positive (CPS ≥1) tumors. Targeted therapies including ramucirumab (anti-VEGFR2 monoclonal antibody) are used as second-line monotherapy or in combination with paclitaxel. Supportive medications include erythropoiesis-stimulating agents for chemotherapy-induced anemia, granulocyte colony-stimulating factors for neutropenia prophylaxis, and bisphosphonates or denosumab for bone metastases.

Surgical treatment remains the only potentially curative modality for non-metastatic gastric cancer. Radical gastrectomy with D2 lymphadenectomy—removal of perigastric (stations 1–6) and celiac axis–adjacent (stations 7–11) lymph nodes—is the global standard for clinical T2–T4 or node-positive disease. Laparoscopic and robotic-assisted D2 gastrectomy are now routinely performed in tertiary Chinese hospitals, offering reduced postoperative pain, shorter hospital stays (median 6–8 days), faster return of gastrointestinal function, and comparable oncologic outcomes to open surgery at 3–5 years. Total gastrectomy is preferred for proximal or diffuse-type (linitis plastica) tumors, while distal or subtotal gastrectomy suffices for distal antral cancers. Reconstruction options include Roux-en-Y esophagojejunostomy (total gastrectomy) or Billroth I/II or Roux-en-Y gastrojejunostomy (subtotal). Postoperative pathology guides adjuvant therapy decisions, with meticulous reporting of margin status (R0 vs R1/R2), lymph node yield (>16 nodes recommended), and tumor regression grade following neoadjuvant therapy.

China offers distinct advantages in gastric cancer management. First, its high incidence (~40% of global cases) has fostered unparalleled clinical expertise and procedural volume—many top-tier hospitals perform >500 gastrectomies annually, correlating with lower perioperative mortality (<2%) and superior long-term survival. Second, China leads in real-world implementation of ESD, with standardized training programs, national ESD quality benchmarks, and AI-assisted endoscopic imaging (e.g., deep learning algorithms for real-time lesion characterization) enhancing diagnostic accuracy. Third, rapid regulatory approval pathways (e.g., NMPA’s conditional approval program) enable timely access to novel agents like fruquintinib (anti-angiogenic TKI) and zolbetuximab (CLDN18.2-targeted therapy), often months ahead of Western markets. Fourth, integrated traditional Chinese medicine (TCM) is evidence-informed adjunctive care: formulas such as Jianpi Yangzheng Xiaoji decoction demonstrate improved tolerance to chemotherapy, reduced fatigue, and enhanced immune parameters in randomized trials—though used strictly as supportive, not alternative, therapy.

Recovery advice emphasizes structured, stage-specific rehabilitation. Post-endoscopic resection patients should adhere to a clear liquid diet for 24 hours, advance to soft foods over 5–7 days, avoid NSAIDs and anticoagulants for 2 weeks, and undergo surveillance endoscopy at 3, 6, and 12 months. After gastrectomy, patients require lifelong nutritional monitoring: small, frequent meals (6–8/day); avoidance of simple carbohydrates to prevent dumping syndrome; supplementation with vitamin B12 (intramuscular or high-dose oral), iron, calcium, and vitamin D; and referral to a registered dietitian. Physical recovery includes early ambulation (day 1 post-op), progressive resistance training to counteract sarcopenia, and pulmonary hygiene to prevent atelectasis. Psychologically, patients benefit from structured counseling addressing body image concerns, fear of recurrence, and adjustment to altered digestion. All patients should undergo annual upper endoscopy and CT surveillance per guidelines (e.g., JSGC or CSCO), with attention to family history—first-degree relatives warrant screening endoscopy starting at age 40 or 10 years younger than the youngest affected relative. Finally, smoking cessation and alcohol abstinence are non-negotiable, given their synergistic carcinogenic effects with H. pylori infection and dietary nitrosamines.