Carcinoma of the Oesophagus

Carcinoma of the oesophagus is a common, agressive tumour which is increasing in frequency.

Several histological types are seen, almost all of which are epithelial in origin. The vast majority of these tumours will be either squamous cell carcinoma (SCC) or adenocarcinoma (AC).

In the last two decades there has been a particular rise in the amount of AC seen,¹ to the extent that this has now overtaken SCC as the most common form of oesophageal tumour in some developed countries.

Incidence

• Carcinoma of the oesophagus represents the fifth most common malignant tumour in the developed world.
• In the UK the incidence is of the order 10 per 100,000 population.
• The number of new cases of AC in the UK is approximately 5 per 100,000 and the UK has the highest incidence of oesophageal AC of all countries from which figures are available.
• Males are more commonly affected by AC than females with a ratio of 7:1,² and for all forms of oesophageal carcinoma with a M:F ratio of 2:1.
• The median age at presentation is 60 years.

The incidence of oesophageal carcinoma varies considerably with geographical location with high rates in China and Iran, where it has been directly linked to the preservation of food using nitrosamines. AC is seen more frequently in Caucasian populations whereas SCC is more frequent in people of African descent. In the last 30 years the incidence of AC has increased more than 350% in the West.

Risk factors

• The use of tobacco and alcohol are strong risk factors for both SCC and AC, and have a synergistic effect in this respect for squamous cell cancer and additive effect for AC. Cigarette smoking is associated with a 10 fold increase in risk for SCC, and a 2-3 fold increase in risk for AC.³The relative increase in risk caused by smoking remains high even after 30 years of giving up smoking for AC, but reduces within 10 years for SCC.⁴
• Barrett's oesophagus, which is a precursor of AC.
• Chronic inflammation and stasis from any cause increase the risk of oesophageal SCC e.g. strictures due to caustic injury or achalasia.
• Tylosis and Plummer Vinson syndrome are also associated with an increased risk for SCC.
• Obesity has been linked with increased risk for AC but reduced risk for SCC. It is thought that this may be due to the fact that obesity increases the risk of gastro-oesophageal reflux disease (GORD), in turn increasing the risk of Barrett's oesophagus.

• Dysphagia
• Weight loss
• Loss of appetite
• Odynophagia
• Hoarseness
• Melaena
• Retrosternal pain
• Intractable hiccups
• Lymphadenopathy

These include:

• Oesophageal stricture from any cause
• Compression of the oesophagus from external sources e.g. enlarged lymph glands or bronchial carcinoma
• Intramural benign tumours e.g. leiyomyoma
• Metastatic tumours - most commonly from breast

The investigation of a patient with symptoms suggestive of oesophageal carcinoma may include:

• Full history - smoking, alcohol, previous GORD or stricture, weight loss, dysphagia, melaena
• Examination - anaemia, lymphadenopathy, evidence of metastases
• FBC
• Fine needle aspiration - of any palpable cervical lymph node
• CXR - looking for evidence of metastases
• Double contrast barium swallow
• CT/MRI scan of chest and upper abdomen - for staging purposes
• Endoscopic ultrasound - increases accuracy of staging
• Fluorodeoxyglucose (FDG)-PET scan - for accuracy of staging
• Endoscopy - with brushings and biopsy of any lesion seen
• ± bronchoscopy - in high oesophageal tumours or if hoarseness or haemoptysis present

Primary treatment modalities include surgery alone or chemotherapy with radiation therapy.^5,6

Supportive non-pharmacological measures

• Many patients will present late in the disease process with unresectable disease. For this group of patients the emphasis will be on palliation and symptom relief.
• Radiotherapy or laser ablation may be of use in reducing tumour bulk, and the use of stents may be useful in the short to mid term to help with swallowing.
• Photodynamic therapy can be used for palliation in advanced disease.⁷
• Nutritional status may be maintained by the use of liquid feeds, enteral nutrition or PEG tubes.

Pharmacological

• Pain relief should be maintained at a level at which the patient experiences little, or no pain.

Surgery

• Oesophagectomy remains the treatment of choice for patients with resectable tumours, although there remains some controversy as to whether or not block dissection of the lymph nodes at the same time confers any added advantage.⁸ Operative mortality is in the order of 2-23%.
• Oesophagectomy may be thorascopically assisted.⁹ This is a minimally invasive procedure. The advantage is quicker recovery and fewer lung complications, but offset by a longer operating time and greater likelihood of incomplete resection.
• Photodynamic therapy (PDT) is an alternative to major surgery.¹⁰ A photosensitising agent is injected and then activated by exposing the tumour to light, usually a low power laser, via an endoscope. The agent absorbs energy from the light and produces high energy oxygen molecules that destroy tumour cells. This is an outpatient procedure, under sedation. One series 5 year disease specific survival was 76% in 56 treated with PDT as monotherapy.
• Pre-operative adjuvant therapy with drugs and radiation is used in some centres. It is advocated by some, however meta-analysis has failed to show any advantage over surgery alone for resectable tumours.^11,12

The patients pre-operative status and co-morbidity are strong predictors of outcome.
The prognosis for oesophageal carcinoma varies depending on the stage at presentation:

• The overall 5 year survival rate for resectable tumours ranges from 10-25%.
• 5 year survival rates for stage 1 oesophageal cancer range from 80-94%
• 5 year survival rates for stage 3 are between 10-14% ¹³

Earlier detection through screening and surveillance will improve survival rates. However, standard diagnostic tools e.g. endoscopy with biopsy, have several limitations as screening tools - including low negative predictive value and relatively high cost.

Recently developed biomarkers such as FISH and improved imaging techniques, may help overcome current problems and provide improved screening and surveillance for oesophageal cancer.¹⁴