Oesophageal Cancer

Oesophageal cancer is a malignant tumour, most common in people over the age of 50, that mainly affects the middle or lower oesophagus and leads to swallowing difficulties. Smoking and heavy alcohol intake are risk factors; people with certain disorders of the oesophagus (such as Barrett’s oesophagus) are also at increased risk.

Symptoms

The tumour is often present for some time before it begins to cause symptoms. Early symptoms may include pain on, and difficulty in, swallowing foods and/or liquids. The patient’ s condition progressively worsens to a point where food is immediately regurgitated and there is rapid weight loss. Regurgitated fluid spilling into the trachea (windpipe) often causes respiratory infections.

Diagnosis, treatment, and outlook

Diagnosis usually involves a barium swallow (see barium X-ray examinations) to detect an obstruction in the oesophagus and a biopsy (removal of a small sample of tissue for microscopic analysis) taken during endoscopy. Treatment depends on whether or not the cancer has spread to surrounding structures. Removal of the oesophagus may be possible in some localized, and early diagnosed, cancer. Radiotherapy may cause regression of the cancer, relieve symptoms, and occasionally cure older patients who might not be suitable for major surgery. Permanent insertion of a rigid tube (a stent) through the tumour, or laser treatment to burn through it, can help temporarily to relieve symptoms and improve nutrition. The outlook depends on whether the cancer has spread at the time of diagnosis. In cases in which there is no spread and surgery is carried out successfully, 50 per cent of patients survive for more than five years. If the cancer is more widespread, less than a quarter of patients survive longer than one year.

Oesophageal Cancer in more detail - technical article

Essentials

A common cancer, usually of squamous cell histology, that is particularly prevalent in China (male incidence 28/100 000), southern and eastern Africa, and Japan. Typical presentation is with dysphagia, initially to solids and then to liquids. Staging investigations include contrast-enhanced CT, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET scan), and endoscopic ultrasonography. In patients who are fit and suitable for surgery, neoadjuvant chemotherapy is commonly given, but most patients are elderly with comorbid disease and unsuitable for curative surgery, and many others present with advanced disease such that palliation with or without systemic therapy is the only option. For locally advanced inoperable patients, chemoradiation in preference to radiation alone may confer a survival benefit. Specific palliation for dysphagia can include laser, brachytherapy, external beam therapy or stenting. Overall survival is less than 40% at 2 years.

Introduction

There are approximately 12 000 new cases of oesophageal cancer in the United Kingdom per year). Mortality rates closely resemble incidence and, despite some progress in diagnosis and treatment, there has been little overall impact on the disease. The incidence of oesophagogastric carcinoma is increasing, with the male European age-standardized rate per 100 000 population rising from 7.8 to 13.4 between 1971 and 2005. The corresponding rates for women were 4.2 to 4.9. Worldwide, there is an 18-fold variation in male incidence rates between different regions and an almost 40 fold variation in female rates. There is also ethnic variation, with a six times higher rate in black men than in white men. Most cases (80–85%) of oesophageal cancer are diagnosed in developing countries, where it is the fourth most common cancer in men. The usual histology is squamous cell carcinoma, although the incidence of adenocarcinoma is increasing. This increase is likely to be environmental, although no single agent has been identified and it is uncertain whether or not it is related to the increase in Barrett’s oesophagus.

Predisposing factors

It has been proposed that the family of Napoleon Bonaparte had a predisposition to stomach cancer, although epidemiological and genetic aetiologies are somewhat wrong-footed by the conclusion that ‘An analysis of Bonaparte’s case may convince one that human predisposition to cancer is a phenomenon of an unstable, variable nature, which is easily broken by marriage’. More classically described is tylosis, a syndrome of familial oesophageal cancer and hyperkeratosis of the palms and soles, as well as thickening of the oral mucosa. For an affected family member, the estimated lifetime risk of cancer is 92% by age 70. The linkage has been localized to chromosome 17q25 and associated with down-regulation of the cytoglobin gene.

Environmental factors that may be incriminated in oesophageal cancer include smoking and high alcohol intake, also achalasia, oesophageal strictures due to ingestion of corrosives, radiotherapy, and coeliac disease. The Paterson–Kelly (Plummer–Vinson) syndrome, characterized by iron deficiency anaemia, glossitis, postcricoid webs, and dysphagia has been associated with squamous carcinoma in up to 20% of cases, most commonly in Scandinavian populations.

Clinical features

Approximately 55% of patients have cancers in the lower section of the oesophagus, 30% in the upper section, and 15% in the middle section. Middle and upper oesophageal cancers are more likely to be squamous cell carcinomas, whereas those in the lower oesophagus are commonly adenocarcinoma, potentially arising from a Barrett’s oesophagus.

Patients classically present with dysphagia, initially to solids and then to liquids. Other late symptoms such as dyspnoea, a hoarse voice, constant pain and weight loss suggest advanced disease and confer a poor prognosis. Initial diagnosis is made at upper gastrointestinal endoscopy or occasionally contrast radiology, and confirmed by endoscopic biopsy. Standard staging investigations include contrast-enhanced CT, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (the FDG-PET scan), and endoscopic ultrasonography.

Management

In patients who are fit and suitable for surgery, neoadjuvant chemotherapy is commonly given and confers an improvement in survival from 34% after oesophagectomy alone to 43% at 2 years. For locally advanced inoperable patients, or patients unfit for surgery chemoradiation in preference to radiation alone may confer a survival of 38% vs 10% at 2 years, although these data come from a small unrepeated study. Attempts to combine surgery and chemoradiation or neoadjuvant chemotherapy and chemoradiation have failed to demonstrate a survival advantage and there is still debate as to the best approach. Surgery

Surgery is performed using a transhiatal or thoracic approach. There is increasing evidence to suggest that a two-phase oesophagectomy (abdomen and right or left chest approach) with a two-field lymphadenectomy (abdomen and thorax) is oncologically favoured, but this remains controversial.

Palliative approaches

Most patients with oesophageal cancer are elderly with comorbid disease and are unsuitable for curative surgery and 40% of patients present with advanced disease in whom palliation is the only option. Specific palliation for dysphagia can include laser, brachytherapy, external beam therapy, or stenting.

Laser endoscopic therapy vaporizes exophytic tumour under direct vision without mechanical stress on the oesophageal wall so that stenting is usually not required. Successful tumour recanalization can be achieved in more than 90% of appropriately selected patients, and a return to eating solids is seen in most patients after treatment. However, laser therapy needs to be repeated every 4–6 weeks as the tumour regrows. The palliation can be improved with radiation, either external beam or brachtherapy.

Palliative chemotherapy improves survival, although this remains poor with a 1 year survival of 40%. It is likely that three drug combinations offer the best results. Survival and prognosis can be predicted using microRNA arrays, but these methodologies have yet to be prospectively validated.