Gastric Carcinoma

Gastric cancer is the second most common cause of cancer-related death in the world. It is a difficult disease to cure in Western countries, mainly because most patients present with advanced disease. 50% involve the pylorus, 25% the lesser curve and 10% the cardia. 2-8% of gastric cancers are lymphomas.

• The incidence in England and Wales for men is 20 per 100,000 and for women 7 per 100,000.¹
• There are unexplained wide international variations, being especially common in Japan, China and parts of South America.
• There has been a marked increase in the incidence of adenocarcinoma of the proximal stomach (especially around the cardia) in the past two decades with a corresponding decrease in incidence in distal gastric cancer.¹

Risk factors

• Increasing age: 90% of gastric cancers occur in those aged over 55 years.²
• More common in men than women.
• Strongly associated with poor socio-economic status.
• Helicobacter pylori: there is a 2.5 fold increased risk of gastric cancer in infected individuals. However the relationship between infection and cancer in the cardia region is currently unclear and it is possible that eradication of Helicobacter pylori may increase the risk of cardia cancer.¹
• Diet: diets containing low levels of fresh fruit and vegetable consumption increase the risk of gastric cancer. A high level of salt and preserved foods may also increase the risk.
• Smoking.
• Atrophic gastritis, pernicious anaemia, post-gastrectomy, Ménétrier's disease.
• Familial risk: families with a very high incidence have been identified. There is a 2 to 3-fold increased risk to first-degree relatives of gastric cancer patients. There is a link between E-cadherin gene mutations and some familial gastric cancers.
• Blood group A (relative risk is 1.2).
• Hypogammaglobulinaemia.

• Non-specific with dyspepsia, weight loss, vomiting, dysphagia and anaemia.
• Early gastric cancer often has symptoms suggesting a benign aetiology. 70% of patients with early gastric cancer only have symptoms of uncomplicated dyspepsia and are not complicated by anaemia, dysphagia, or weight loss.
• Clinical diagnosis is therefore very inaccurate in distinguishing between organic and non-organic disease. All at-risk patients with dyspepsia should be considered for endoscopy.
• The majority of patients present with advanced disease and alarm symptoms such as weight loss, vomiting, anorexia, abdominal pain and anaemia.
• Treatment with antisecretory drugs may delay diagnosis or result in a misdiagnosis on first endoscopy. Proton pump inhibitors may appear to heal malignant ulcers and so a diagnosis needs to be established before such agents are used in at risk patients.³
• Signs suggesting incurable disease, e.g. epigastric mass, hepatomegaly, jaundice, ascites, Troisier's sign (an enlarged left supraclavicular node - Virchow's node), acanthosis nigricans.

Immediate referral

• Significant acute gastrointestinal bleeding

Urgent referral (within 2 weeks)

• Patients of any age with dyspepsia who present with any of the following should have an urgent referral for endoscopy or referral to a specialist in upper gastrointestinal cancer:
  • Chronic gastrointestinal bleeding
  • Progressive dysphagia
  • Progressive unintentional weight loss
  • Persistent vomiting
  • Iron deficiency anaemia
  • Epigastric mass
  • Suspicious barium meal result
• Patients aged 55 years and older with unexplained and persistent recent-onset dyspepsia
• Patients presenting with the following, even in the absence of dyspepsia, should have an urgent referral for endoscopy or referral to a specialist in upper gastrointestinal cancer:
  • Dysphagia
  • Unexplained upper abdominal pain and weight loss, with or without back pain
  • Upper abdominal mass
  • Obstructive jaundice (depending on clinical state)
• Consider urgent referral for:
  • Persistent vomiting and weight loss in the absence of dyspepsia
  • Unexplained weight loss
  • Iron deficiency anaemia
• Consider urgent referral for patients with unexplained worsening of their dyspepsia who are known to have any of the following risk factors:
  • Barrett's oesophagus
  • Dysplasia
  • Atrophic gastritis (pernicious anaemia)
  • Intestinal metaplasia
  • Peptic ulcer surgery more than 20 years ago
• Helicobacter pylori status should not affect the decision to refer for suspected cancer

• Check full blood count (possible anaemia) and liver function tests.
• Rapid access flexible endoscopy is the investigation of choice. Biopsies can be taken and small lesions evaluated more fully than is possible with radiological studies. Antisecretory therapy should be ideally withheld until after endoscopy to avoid misdiagnosis.
• All gastric ulcers should be biopsied (multiple ulcer edge biopsies), as even malignant ulcers may appear to heal on drug treatment. Gastric ulcers should also be followed up until healing with repeat biopsy.

Patients with gastric cancer should undergo careful pre-operative staging to enable appropriate management.

• Spread is local, lymphatic, blood-borne and trans-coelomic, e.g. to ovaries (Krukenberg's tumour).
• Initial staging assessment should include spiral CT of the thorax and abdomen to determine the presence or absence of metastatic disease.
• In the absence of metastatic disease, assessment of operability is preferably made by endoscopic ultrasound.
• Adjuncts to staging include chest radiography, trans-abdominal ultrasound, magnetic resonance imaging, bronchoscopy and laparoscopy.

• All patients with gastric cancer should be screened for nutritional deficiency and consideration of nutritional support.⁵
• Symptom control includes treatment for pain, nausea, constipation, depression and mouth care.

Surgery

• Surgery is the treatment of choice for gastric cancer. The most important indicator for resectability and survival after surgery is early diagnosis and therefore early stage of disease at operation. Perioperative mortality is about 2%.
• Distal (antral) tumours should be treated by subtotal gastrectomy and proximal tumours by total gastrectomy.
• Limited gastric resections should presently only be used for palliation or in the very elderly.
• Patients with curable cancers of the stomach should undergo a D2 lymphadenectomy (removing distant lymph nodes). Excision of the primary lesion together with the omenta and first two tiers of lymph nodes (N1 and N2) that drain the affected area of the stomach can cure patients, even in the presence of lymph node metastases.¹
• The distal pancreas and spleen should not be removed as part of a resection for a cancer in the distal two thirds of the stomach. There is increasing evidence that removal of the spleen has an adverse effect on prognosis. The distal pancreas should be removed only when there is direct invasion and still a chance of a curative procedure in patients with carcinoma of the proximal stomach. Resection of the spleen and splenic hilar nodes should only be considered in patients with tumours of the proximal stomach located on the greater curvature/posterior wall of the stomach close to the splenic hilum where the incidence of splenic hilar nodal involvement is likely to be high.

Chemotherapy and radiotherapy

• There is insufficient evidence to state with any certainty whether adjuvant chemotherapy without radiotherapy after surgery is helpful.⁶
• Post-operative chemoradiotherapy has been shown to improve survival in the short-term (median 3.3 year follow up) but has yet to be evaluated fully for long-term benefit.^7,8
• Intraperitoneal chemotherapy remains investigational.
• 5-FU is the most effective chemotherapeutic agent. A combination of 5-FU with other agents is superior to single agent treatment. Various combinations are being explored including the combination of epirubicin, cisplatin and continuous infusion of 5-FU (ECF)⁹ and bi-weekly infusions of 5-FU, eucovorin, oxaliplatin and docetaxel.

Palliative care

• A multidisciplinary approach to care is essential.
• Palliative care is often needed for obstruction, pain or haemorrhage and involves judicious use of drugs, surgery and radiotherapy.
• Palliative chemotherapy for locally advanced and/or metastatic disease provides quality of life and survival benefit. Various combinations are being explored including epirubicin, cisplatin and continuous infusion of 5-FU (ECF)⁹ and twice-weekly oxaliplatin, leucovorin, fluorouracil and docetaxel.¹⁰ Pre-operative downstaging of locally advanced disease with chemotherapy may enable resection of previously inoperable cancers.
• Currently there is no indication to recommend second-line chemotherapy. Its role should remain in the context of a clinical trial. Second-line palliative chemotherapy following failure of first-line chemotherapy is still investigational but trials of docetaxel and epirubicin, and also of irenotecan, have demonstrated significant benefits.¹¹
• Those with distal obstructing tumours may benefit from a subtotal gastrectomy or gastrojejunostomy. Stenting of gastric cardia tumours relieves dysphagia.
• Endoscopic laser therapy may be of help in unresectable obstruction or to control bleeding lesions.
• Blood transfusion may be appropriate for symptomatic anaemia.
• Corticosteroids or megestrol acetate should be considered for management of anorexia.⁵
• Coeliac plexus nerve blocks may be effective in controlling resistant pain.

• The overall 5-year survival rate varies from almost nil for patients with disseminated disease to almost 50% survival for patients with localised resectable distal gastric cancers.
• Even with apparent localised disease, the 5-year survival is only 10% to 15% in patients with proximal gastric cancer.
• Stage 0 gastric cancer confined to mucosa has a >90% 5-year survival after gastrectomy with lymphadenectomy but gastric cancer is seldom diagnosed at this stage outside Japan.
• Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon.

• A diet with high intakes of fruit and vegetables (at least five servings per day), smoking cessation and reduction of excessive alcohol intake are likely, although not yet proven, to reduce the incidence of gastric cancer. Vitamin supplements are not known to have any effect.
• It is not known whether the mucosal changes induced by longstanding Helicobacter pylori infection are reversible and whether eradication will therefore influence the development of cancer.