Gastric Cancer

Gastric cancer is the fifth most common cancer globally and is the second highest cause of cancer related deaths, mostly due to patients presenting late with advanced disease.

The majority (>90%) of gastric cancers arise from the gastric mucosa as adenocarcinomas. The remainder are a mixture of connective tissue, lymphoid or neuroendocrine malignancies.

In this article, we shall look the risk factors, clinical features and management of a patient with gastric cancer.


Risk Factors

In many Western countries, rates of gastric cancer have fallen dramatically in the past few decades (mainly due to an improved diet and treatment of Helicobacter Pylori infections). However, it remains extremely common in Far Eastern countries such as Japan and Korea.

The major risk factors for developing gastric cancer include:

  • Male
  • Helicobacter Pylori infection
  • Increasing age
  • Smoking
  • Diet heavy in salt
  • Heavy alcohol consumption
  • Family history
  • Pernicious anaemia

Helicobacter Pylori

Fig 1 - Scanning electron micrograph image of H. Pylori.

Fig 1 – Scanning electron micrograph image of H. Pylori.

The most important modifiable risk factor identified in developing gastric cancer is infection of the stomach mucosa by Helicobacter Pylori. A recent meta-analysis investigating the relationship between H. Pylori and gastric cancer estimated that the risk was nearly six times higher for H. Pylori-infected people than for uninfected people.

H. Pylori is a Gram negative helical bacterium that produces the urease enzyme, acting to break down urea into COand ammonia. The ammonia neutralises stomach acid, allowing the bacterium to create an alkaline microenvironment. It subsequently sets off a cycle of repeated damage to the epithelial cells, leading to inflammation, ulceration, and ultimately gastric neoplasia.

Whilst around 60% of the world’s population are infected with H. Pylori, less than 0.5% will develop gastric adenocarcinoma.


Clinical Features

The symptoms of gastric cancer are frequently vague and non-specific, with patients often presenting at an advanced stage.

The common presenting symptoms include dyspepsia, dysphagia, nausea & vomiting, melena and haematemesis. Non-specific cancer symptoms (anorexia, weight loss, or anaemia) are markers of late stage disease.

Fig 2 - Acanthosis nigricans, hyperpigmentation of the skin creases.

Fig 2 – Acanthosis nigricans, hyperpigmentation of the skin creases.

On examination, clinical signs are usually completely absent, especially in the early stages. In advanced disease, findings include:

  • Signs of anaemia – e.g. pale conjunctiva.
  • Jaundice and hepatomegaly – secondary to liver metastasis.
  • Acanthosis nigricans –  hyperpigmentation of the skin creases, a non-specific sign seen in gastric cancer
  • Trossier’s sign –  an enlarged Vircow’s node.
  • Palpable epigastric mass

In the UK, only 40% of patients with gastric cancer are diagnosed via the urgent pathway. The rest are diagnosed after a non-urgent referral, an emergency hospital admission, or were referred by another hospital specialist. It is therefore important to remember that anorexia or weight loss are markers of late stage disease rather than being essential for diagnosis. If in doubt, patients should be referred for endoscopy.


Differential Diagnosis

Gastric cancer often presents with non-specific symptoms, and consequently there are a wide range of potential differential diagnoses.

Important diagnoses to consider include peptic ulcer disease, GORD, and pancreatic cancer.


Investigations

Laboratory Tests

Any patient presenting with clinical features of gastric cancer, including haematemesis or melena, will warrant a full blood count. Liver function tests may also be requested if there is any evidence of liver metastases.

A CEA (carcinoembryonic antigen) is a marker of gastric malignancy and will be positive in 50% of patients with gastric cancer. However, practically it is of little use in the diagnosis of the disease and many centres do not test for it routinely.

Imaging

The primary investigation of any suspected gastric cancer is an urgent upper GI endoscopy, allowing for direct visualisation of any malignancies and any biopsies taken as needed.

Biopsies from suspected gastric malignancies can be sent for:

  • Histology – for classification and grading of any neoplasia present
  • CLO test – for the presence of H. Pylori.
  • HER2/neu protein expression – this will allow for targeted monoclonal therapies if present.

NICE guidelines suggest a cancer pathway referral for any patients presenting with symptoms suggestive of an upper GI malignancy. Specifically, any patients with dysphagia or >55yrs with weight loss and upper abdominal pain, dyspepsia, or reflux requires an urgent endoscopy. A non-urgent endoscopy is suggested in those with haematemesis alone.

CT scan may show thickening of the gastric wall but does not allow direct visualization or biopsy (and hence firm tissue diagnosis, which is required before starting treatment). It is therefore only an acceptable alternative in patients who are unfit for any invasive treatment (including chemotherapy).

Fig. 3 - (A) Early stage gastric cancer (B) Linitis Plastica, whereby the malignancy has invaded most of the stomach and produced a 'leather-bottle' type appearance

Fig. 3 – (A) Early stage gastric cancer (B) Linitis Plastica, whereby the malignancy has invaded most of the stomach and produced a ‘leather-bottle’ type appearance

Staging Investigations

In order to plan treatment, all patients need a CT Chest-Abdomen-Pelvis and a staging laparoscopy (to look for peritoneal metastases). The most commonly used staging system for gastric cancers is TNM.

As gastric cancers are not very “PET avid” (do not take up the radioactive tracer well), PET scans are rarely used in staging gastric cancers.


Management

All patients should be discussed at a specialist upper GI cancer multi-disciplinary team meeting.

Ensuring adequate nutrition is essential and challenging in these patients. Each patient should undergo nutritional status assessment and be seen by a dietician if necessary. Many patients need formal nutritional support via a nasogastric tube or a RIG (radiologically inserted gastrostomy) tube.

Curative Treatment

The mainstay of curative treatment is surgical. Patients who are fit enough should be offered peri-operative chemotherapy (3 cycles of neoadjuvant chemotherapy before surgery and then, if still fit post-op, 3 cycles of adjuvant chemotherapy afterwards*).

*This based on the MAGIC trial which showed a 13% 5-year survival advantage in patients who received peri-operative chemotherapy compared to those who underwent surgery alone. The chemotherapy regime used was epirubicin, cisplatin and 5-FU (ECF). 5-FU is usually replaced by its oral form, capecitabine.

The aim of surgery is to achieve loco-regional control by removing the tumour and its local lymph nodes:

  • Proximal gastric cancers – total gastrectomy.
  • Distal gastric cancers (antrum or pylorus) – subtotal gastrectomy.

Many methods of reconstructing the alimentary anatomy have been tried historically. The most commonly used method is the Roux-en-Y reconstruction as it gives the best functional result, in particular with less bile reflux.

Patients with T1a tumours (tumours confined to the muscularis mucosa) may be offered an Endoscopic Mucosal Resection (EMR). This has the advantage of a greatly reduced morbidity, mortality and quality of life impact. However, it can only be used in early tumours due to the risk of local lymph node invasion in tumours that have invaded beyond the muscularis mucosae, making its use in clinical practice quite rare.

Fig 4 - Total gastrectomy and Roux-en-Y reconstruction

Fig 4 – Total gastrectomy and Roux-en-Y reconstruction

Gastrectomy Complications

Gastrectomy is a major operation. Mortality rates remain between 2-5% and quality of life remains poor for up to 6 months after surgery.

Specific complications include death (3-5%), anastomotic leak (5-10%), re-operation, dumping syndrome, and vitamin B12 deficiency (patients need 3-monthly vitamin B12 injections).

Palliative Management

Palliative options include chemotherapy, best supportive care, stenting (for patients who have gastric outlet obstruction secondary to an obstructing cancer), or surgery.

Surgical palliative care (usually distal gastrectomy or bypass surgery) is best used when stenting fails or is not available, yet can also be used (cautiously!) for palliation of bleeding tumours.


Complications

The main complications of gastric cancers are gastric outlet obstruction, iron deficiency anaemia, perforation and malnutrition.

The 10-year survival rate for stomach cancer overall is 15%, yet this will vary depending on staging. Most gastric cancers will present at an advanced stage with metastasis, which have a 5 year survival of <5%.

Further Reading

Gastric cancer
Van Cutsem E et al., The Lancet

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