The oesophagus is the muscular tube that connects the bottom of the neck with the stomach, carrying food though the chest. The muscles in the tube push lumps of chewed food downward. The cells lining the oesophagus are mainly squamous cells, which are flat. However, the cells in the bottom part of the oesophagus can change into ones that are similar to those found in the stomach if, over time, acid reflux/ heartburn has been present.
There are therefore two main types of oesophageal cancer: Squamous Cell Cancer and Adenocarcinoma.
The two main types of oesophageal cancer have both separate and overlapping causes.
Squamous Cell Cancer of the Oesophagus
Smoking and Drinking are the main risk factors for this disease
Eating foods that contain certain nitrogen chemicals, such as pickled vegetables, increases the risk of oesophageal cancer (as does Betel nut chewing). An increase in the incidence has been seen in regions where tea is drunk at very hot temperatures.
It is thought that Zinc may be protective.
Individuals who have a disease called ‘achalasia’, where the muscles of the oesophagus do not move well, are at increased risk, as are those who have chemically caused narrowing’s. Tylosis is another disease that has a raised risk of developing squamous cell oesophageal cancer; it causes a darkening of the palms and soles and is an inherited condition.
Adenocarcinoma of the Oesophagus
It is thought that virtually every case of adenocarcinoma of the oesophagus arises from an area of the lining of the oesophagus that has undergone a change. This change happens because acid, formed in the stomach has been washing over the lining for a long time. This process turns the cells lining the oesophageal lumen into ones that resemble those found in the stomach. These changes are called Barrett’s oesophagus. Patients with this may have had heartburn for a long time, but as many as 40% of people with Barrett’s oesophagus have not had any symptoms.
Barrett’s oesophagus is a premalignant condition detected in the majority of patients with oesophageal or gastro-oesophageal adenocarcinoma – cancers that, once established, have a low survival rate (perhaps 5-15% five year survival).
Barrett’s oesophagus is diagnosed in approximately 15% of patients undergoing oesophagoscopy for for reflux/oesophagitis symptoms and is an important condition because of its premalignant status. The progression from low grade dysplasia Barrett’s to high grade (as detected by a biopsy of the affected area at the bottom of the oesophagus) is a sinister development with a higher risk of imminent frank malignant change.
Smoking may increase the risk of oesophageal adenocarcinoma, but the association is not as strong as with squamous cell carcinoma.
Obesity is a definite risk factor, probably because it increases the risk of Barrett’s Oesophagus, described above.
Oesophageal cancer is becoming more common. In 2004 there were 6600 cases in the UK, accounting for 3% and 2%of all cancers in men and women respectively. It is the adenocarcinomas that tend to occur in the looser part of the oesophagus that is increasing in incidence.
Symptoms & diagnosis: Oesophageal cancer
The first symptom is usually difficulty in swallowing, first to very solid, dry foods, but then progressing to less solid food. There may be a sensation of the food sticking that goes away with drinking fluids to force the food past an obstruction. Weight loss and a reduced appetite are also possible.
Chest pain is possible, and sometimes coughing immediately after swallowing can occur if an abnormal connection between the swallowing tube and the breathing tube (trachea) has been made by the tumour.
If a patient has difficulty swallowing the first investigation that is done is usually an X ray taken whilst swallowing a liquid that shows up on X ray pictures. This is called a Barium Swallow. It shows up narrowing’s in the oesophagus and areas where the lining is irregular. If there is an abnormality, the next usual test is an endoscopy.
This uses a flexible camera that is passed through the mouth in to the throat and then down the oesophagus. The procedure is done under sedation, i.e. the patient is given a medicine to make them sleepy to reduce the discomfort of the procedure.
The endoscopy allows the doctor to look directly at the oesophagus and to take a sample (a biopsy) of any abnormal areas.
These samples are examined under the microscope to look for cancer cells. The type of the cancer can also be determined.
The ‘stage’ of any cancer is a description of its size, local spread and distant spread. Defining the stage is crucial in deciding the most appropriate treatment and whether it is possible to aim to cure the disease. Scans are the most important method of working out the stage of the disease.
Oncologist will use internationally recognised systems of staging, but the principles are to decide the following:
The main concern whether the growth is confined to the oesophagus or whether it has spread to other organs.
Where the disease is localised then it may be possible to aim for a cure, otherwise palliation is the best approach.
Treatment & outcomes: Oesophageal cancer
The treatment of oesophageal cancer depends on the aim of therapy, which in turn is decided on by considering the stage of the disease and how well the patient is.
When the tumour is only at the oesophagus, then it may be possible to aim to cure the disease.
The exact treatment then depends on the type of oesophageal tumour present.
For most adenocarcinomas (usually occurring towards the distal end of the stomach), an operation is required. Furthermore, unless the tumour is very small, then the potential success of the treatment may be improved by 2 to 3 courses of chemotherapy before the operation.
These cancers may arise in an area of Barrett’s oesophagus – an inflammation of the mucosa/lining of the distal oesophagus, which may precede the cancer by many years and requires careful endoscopic follow-up, once found, as part of a ‘screening programme for this disease. (Occasionally, a ‘mucosal stripping procedure may pre-empt cancer developing in this condition). Adenocarcinoma of the distal oeasophagus my have all the characteristics of a stomach adenocarcinomoa (the common type of gastric cancer, including the occasional expression of the driving oncogene: Her-2. This is important as the drug trastuzumab/Herceptin will have a role, usually in conjunction with taxane based chemotherapy in the systemic therapy (as may the ‘smart’ drug: Ramucurumab).
The operation itself is major and removes a long length of the oesophagus (to get clear margins above and below the cancer), either through incisions in the abdomen and left neck, or through on in the abdomen and the side of the chest. The stomach is pulled up to fill the gap – see figure. It is important this sort of surgery is done in a centre where it is performed routinely, and by a specialised surgeon. Patients also should be fit for such a major operation.
After the operation, the details of the resected specimen are considered and further chemotherapy may be given, particularly if it was given before the operation. Some oncologists recommend a combination of chemotherapy and radiotherapy, particularly if the ‘safety margin’ around the tumour is narrow.
For Squamous Cell Carcinomas, if the tumour is small and the patient is fit, then an operation as described above is usually offered. In larger tumours that are still potentially curable, then a combination of chemotherapy and radiotherapy given at the same time may be chosen. It has been shown that the success rate of chemoradiotherapy may be the same as surgery. The radiotherapy is given on a daily basis, Monday to Friday, for 5 to 6 weeks. The chemotherapy is given at the beginning and towards the end of the radiotherapy course. The usual drugs used are Cisplatin and 5-Flourouracil. Chemo-radiotherapy is quite tough treatment which has a number of side effects, including tiredness, sore swallowing and nausea and vomiting – usually occurring maximally towards the end of the radiotherapy and taking several weeks after therapy to subside. Regular blood tests need to be done as well.
Sometimes the aim of the treatment is to control the disease as well as possible, aiming to help the patient live as long as possible as well as possible. Primarily, the aim is to ease symptoms and maximise quality of life, but not to cure.
The best way of improving severe swallowing difficulties is by placing a stent across any obstruction in the oesophagus. A stent is an expandable tube that can be placed within the tumour and will then hold open the tube to allow food to pass down. If the obstruction is very tight, or the tumour is very high or low in the oesophagus, placing a stent is not possible. However, when it can be used, it improves swallowing problems relatively quickly.
If a stent cannot be placed, then a feeding tube may need to be placed directly through the abdominal wall into the stomach. This allows liquid food to be given, maintaining the patients nutrition if they cannot swallow. It also allows medicines to be given as required.
Radiotherapy can be given to help improve swallowing. The treatment is usually given over 1 to 3 weeks, either daily or twice a week. The treatment has relatively few side effects but can take a few weeks to have an effect on the tumour to improve swallowing.
Chemotherapy can also be given to shrink the tumour and attempt to treat cancer that may have spread to other places. Chemotherapy has a number of side effects and the potential benefit must be carefully weighed against the disadvantages.
Other ways of treating oesophageal tumours to open any obstructions and improve swallowing include laser treatment that may vaporise the tumour and ‘brachytherapy’. This is where radiotherapy can be given from a narrow tube placed inside the oesophagus, so the treatment is delivered very close to the tumour whilst minimising the dose to nearby organs.
What to do when the cancer is resistant to the foregoing therapies or has spread/metastasised?
The need to assess whether any adenocarcinomas of the gastrointestinal junction have a driving mutation: e.g. Her-2, which is ‘druggable’ should be tested. and a wider genomic profile is probably worthwhile, albeit with a minority chance of finding another druggable mutation.
Newer ‘smart’ drugs like Ramucurumab may be of therapeutic use for distal oesophageal adenocarcinoms, which resemble gastric cancer – particularly whe the genomics testing does not suggest a hopeful alternative.
For other cancers, it is worthwhile seeing if there is hypermutation (e.g. MMR deficiency) or PDL1 expression at high level as both these predict for response to immunotherapy.
Secondline chemotherapy can be helpful, but usually only brings temporary responses and the overall long term prognosis for metastatic oesophageal cancer is not good.
Credit: Dr. P. N. Plowman MD> The Oncology Clinic, 20 Harley Street, London W1G 9PH. (Advanced Genomics). Tel: +44-207-631-1632
For patients who are reasonably fit and have localised disease on scanning, then cure is a possibility. It is impossible to give an individual patient an exact timescale, and hard to generalise information applied to studies of hundreds or thousands of patients.
The prognosis depends partly on the stage of the disease and how well the tumour responds to treatment. Many doctors will give a percentage probability of survival after a certain time period. However, one does not know how well a patient will do until after the treatment is given and some patients will be cured and some will suffer a return of the disease soon after the end of treatment.
There is no screening programme for oesophageal cancer, given its relative rarity. If patients have a very strong family history of ‘Tylosis’, then a screening programme may be individualised for them.
Patients with Barrett’s oesophagus have a perhaps 1% chance per year of contracting oesophageal cancer, but this risk rises to as high a 5% per year if there are ‘high grade’ changes on biopsy of the affected area at the lower end of the oesophagus); screening/surveillance oesophagoscopies are recommended. The intervals between these oesophagoscopies is debated and perhaps once every three years is enough for those with low grade changes on biopsy. However, for those with high grade (dysplastic) changes on biopsy, either more frequent oesphagoscopies or even recourse to early surgery (or endoscopic mucosal resection) is recommended.