Gastric cancer

• The stomach is divided into 5 anatomical components:

  • Cardia - entry into the stomach
  • Fundus
  • Body
  • Antrum
  • Pylorus - entry into the duodenum
• The whole whole stomach is composed of columnar epithelium
• The majority of gastric cancers are adenocarcinomas, the rest are mostly lymphomas
• Adenocarcinomas are histologically divided into two subtypes:

  • Intestinal type - most common
  • Diffuse type
• Epidemiology:

  • Highly variable depending on the geographical location
  • More common in older people, >50% of patients in UK being over 75 years old
  • More common in men
  • Strongly linked to environmental factors
• The gram negative bacterium Helicobacter pylori has a significant role in the aetiology of gastric cancer.
• Environmental risk factors:

  • Smoking - increased risk of gastritis, peptic ulcers and malignancy
  • High salt intake - risk combined with presence of H. pylori infection
  • Inadequate intake of fruit and vegetables
  • Meat consumption
• H. pylori

  • Gram negative spiral bacterium that colonises the stomach
  • Causes both acute and chronic inflammation that promotes abnormal cellular growth, genetic mutations and dysplasia
  • Oncogenic CagA protein
• Patient related risk factors:

  • Genetic polymorphisms
  • Pernicious anaemia
  • Hereditary diffuse gastric cancer
• Hereditary diffuse gastric cancer:

  • Autosomal dominant
  • Mutations in the CDH1 gene
  • Median age at diagnosis is 38 years
  • Usually undergo prophylactic total gastrectomy
  • Also increased risk of lobular breast cancer
• The Correa cascade describes the classic sequence of histological lesions for adenocarcinoma:

  1. Normal gastric mucosa
  2. Chronic non-atropic gastritis
  3. Chronic atropic gastritis
  4. Intestinal metaplasia
  5. Dysplasia
• Distal e.g. antrum or pylorus cancers are more likely to be intestinal type and associated with H.pylori infection
• Symptoms:

  • Constitutional symptoms - fevers, lethargy
  • Dysphagia - involvement of gastric cardia
  • Indigestion
  • Dyspepsia
  • Nausea/vomiting
  • Haematemesis/melaena
  • Post-prandial fullness
• Signs:

  • Pallor - anaemia
  • Cachexia
  • Lymphadenopathy - Virchow node
  • Hepatomegaly - metastasis
  • Sister Mary Joseph nodule - periumbilical metastasis
• Spread:

  • Direct spread into the transverse colon - can results in a gastrocolic fistula which can cause faecal vomiting
  • Remote lymph node spread - Virchow lymph node via the thoracic duct, giving a palpable mass (Troisier sign)
  • Haematogenous spread - liver, lungs, brain and bone
• Paraneoplastic syndromes:

  • Acanthosis nigricans - velvety hyperpigmentation of the skin, usually in skin folds e.g. axilla
  • Dermatomyositis - inflammatory myopathy characterised by a helicotropic rash (purple rash around the eyes) and Gottron's papules (red areas over the knuckles)
  • Erythema gyratum repens - erythematous rash with a ring shaped appearance. Usually involves the limbs and trunk.
• Gastric outlet obstruction:

  • When there is obstruction to emptying of the stomach at the pylorus
  • Due to fibrotic stricture or obstructing tumour
  • Early satiety, abdominal fullness, nausea, vomiting and weight loss
  • On auscultation of the stomach there may be a succussion splash - sloshing sound heart on patient movement due to a full stomach
• 2WW:

  • Upper abdominal mass consistent with gastric cancer
  • Dysphagia
  • >55 years with weight loss and one of: upper abdominal pain, reflex or dyspepsia
• Gastric cancer is diagnosed using upper GI endoscopy (gastroscopy) and biopsies of suspected lesions
• Human epidermal growth factor receptor 2 (HER2) testing should be completed on patients with metastatic gastric cancer as treatment directed against the HER2 receptor may be used in treatment regimens.
• Cancer stage is based on tumour size, presence of lymph node involvement and distant spread. We call these three factors ‘TNM’ (tumour, nodes, metastasis).
• Treatment options:

  • Surgery: resection of gastric or gastro-oesophageal tumours (e.g. gastrectomy).
  • Endoscopic techniques: mucosal resection or mucosal dissection
  • Radiotherapy: use of high energy rays to destroy cancer cells.
  • Chemotherapy: use of anti-cancer medications to destroy cancer cells
  • Targeted cancer drugs: monoclonal antibodies against certain receptors (e.g. HER2)
  • Palliative care: use of chemotherapy or radiotherapy for disease or symptom control without aiming to cure
  • Best supportive care: focus primarily on symptoms and quality of life without systemic treatments.
• Surgery:

  • Involves removal of the whole stomach or only a portion. The remaining stomach or oesophagus is then joined to the jejunum:
  • Subtotal gastrectomy
  • Total gastrectomy
  • Oesophago-gastrectomy
• The 5 year survival of gastric cancer is poor at around 20%
• Troisier sign:

  • Palpable left supraclavicular node (Virchow's node)
  • Sign of metastatic abdominal malignancy
  • Typically gastric malignancy
• Acanthosis nigricans:

  • Paraneoplastic syndrome of gastric cancer
  • Dark, thick and velvety skin in body folds and creases (typically armpits, groin and neck)
  • Caused by certain cytokines produced by tumour stimulating keratinocytes, melanocytes and fibroblasts
  • Also stimulated by hyperinsulinemia so also seen in obesity, T2DM and PCOS
• Type of gastric cancer depends on cell involved:

  • Columnar epithelium = adenocarcinoma
  • Special nerve cells = GIST (gastrointestinal stromal tumour)
  • Immune system cells = lymphoma
  • Neuroendocrine cells (G-cells) = carcinoid
• Intestinal adenocarcinoma:

  • Most common
  • Can be further subdivided
  • Tend to be bulky tumours e.g. fungating mass or malignant ulcers
• Diffuse adenocarcinoma:

  • Less common
  • Not bulky, more infiltrative - spreads extensively below mucous membrane causing wall thickening and rigidity
  • Entire stomach contracts and looks like a leather bottle - lintis plastica
  • Classically signet cells seen on histology
  • Worse prognosis
• Risk factors:

  • Age (60-70)
  • Male
  • H. pylori and EBV
  • Autoimmune atropic gastritis - causes pernicious anaemia
  • Previous stomach surgery
  • Family history/genetics
  • Diet - carcinogens, smoked fish, meat and salt
  • Smoking
  • Alcohol
  • Obesity
  • Blood group A - increased risk of H.pylori
• Lab tests:

  • Bloods: FBC, U+Es, LFTs(mets), bone profile(mets), clotting screen
  • Consider checking iron studies - some evidence iron deficiency increases risk of gastric cancer
  • Consider checking for pernicious anaemia (risk factor)
• Special tests:

  • Upper GI endoscopy - OGD for visualisation and biopsy
  • Biopsy sent for:
  • Histology - classify and grade neoplasm
  • Clo test - H. pylori
  • Immunochemistry to plan treatment
• Staging:

  • CT TAP to look for metastases (many have these at diagnosis)
  • Staging laparoscopy - CT scan can miss small nodules on stomach serosa, peritoneum, omentum and liver surface
  • PET scan - radiolabelled glucose, high uptake by cancer cells. Monitor disease progression or recurrence
• Management:

  • Upper GI MDT discussion
  • Review nutrition
  • Surgery to resect cancer e.g. partial or total gastrectomy
  • Endoscopy - mucosal resection
  • Radiotherapy
  • Chemotherapy
  • Targeted drugs - e.g. HER2 receptor positive
  • Palliative care e.g. pyloric stent for gastric outlet obstruction
• Troisier sign is the presence of a palpable left supraclavicular node (Virchow node) and is considered a sign of metastatic abdominal malignancy (typically gastric)