Oesophageal Cancer
October 24, 2017
ORLISTAT
October 24, 2017
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​Oesophageal Cancer

Epidemiology

Carcinoma of the oesophagus is a common, aggressive tumour. 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).

Over a period of two decades the incidence of SCC has remained relatively stable or declined (particularly associated with smoking and alcohol), whilst there has been a rapid rise in the amount of AC seen, particularly in Caucasian males. This has now overtaken SCC as the most common form of oesophageal tumour in some developed countries.

The majority of cases (80-85%) are diagnosed in less developed countries; most of these are SCC.

Incidence

Carcinoma of the oesophagus is the 8th most common cancer in the world. Annual incidence of 18.0 per 100,000 in men and 8.5 per 100,000 in women. The male:female ratio for the adenocarcinoma subgroup is 52:10.

An average of 42% of cases were diagnosed in people aged 75 years and over, with more than eight out of ten (83%) occurring in those aged 60 and over.

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.

Hazardous aspects

The use of tobacco and alcohol are strong risk factors for both SCC and AC and have a synergistic effect in this respect for SCC and additive effect for AC. Cigarette smoking is associated with a 10-fold increase in risk for SCC and a 2- to 3-fold increase in risk for AC.

The relative increase in risk caused by smoking remains high for AC, even after 30 years of giving up smoking, but reduces within 10 years for SCC.

Barrett’s oesophagus, which is a precursor of AC.

Chronic inflammation and stasis from any cause increase the risk of oesophageal SCC – eg, strictures due to caustic injury or achalasia.

Tylosis and Paterson-Brown-Kelly syndrome are also associated with an increased risk for SCC. Obesity has been linked with increased risk for AC but reduced risk for SCC. Obesity increases the risk of gastro-oesophageal reflux disease (GORD), in turn increasing the risk of Barrett’s oesophagus.

The relationship between obesity and the rise in AC has, however, been questioned. A review of the Connecticut Tumor Registry data between 1940-2007 showed that the increase in AC seen in the 1960s predated the rise in obesity by a decade. The authors of the review propounded that this may have been linked to a decrease in the incidence of Helicobacter pylori infection or environmental factors.

One Japanese study showed a link between oesophageal cancer and tooth loss.

A family history of hiatal hernia is a risk factor for oesophageal adenocarcinoma, and some people appear to have a genetic predisposition to developing types of gastro-oesophageal cancers.

Appearance

The classic RED FLAG symptoms are:

Dysphagia.

Vomiting.

Anorexia and weight loss.

Symptoms of gastrointestinal-related blood loss.

Oesophageal cancers often present late in the progress of the disease, because approximately 75% of the circumference of the oesophagus must be involved before symptoms of ‘food sticking’ are experienced. As a result, approximately half of the patients who present as a result of developing symptoms, will already have an unresectable tumour or distant metastases.

Symptoms and signs of oesophageal cancer which may cause a patient to present to a doctor include:

Dysphagia

Weight loss

Loss of appetite

Odynophagia

Hoarseness

Melaena

Retrosternal pain

Intractable hiccups

Lymphadenopathy

Distinguished Interpretation

These include:

Oesophageal stricture fromany cause.

Compression of the oesophagus from external sources – eg, enlarged lymph glands or bronchial carcinoma.

Achalasia

Gastric cancer

Intramural benign tumours – eg, leiomyoma. Metastatic tumours – most commonly from breast.

Investigations

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

FBC, U&E, LFT, glucose, CRP.

Urgent endoscopy – with brushings and biopsy of any lesion seen.

Other possible staging investigations include:

CXR – looking for evidence of metastases. Double-contrast barium swallow.

CT/MRI scan of the chest and upper abdomen – for staging purposes.

Fluorodeoxyglucose positron emission tomography (FDG-PET) scan – for accuracy of staging (combined with CT).

Less commonly:

Endoscopic ultrasound – increases accuracy of staging.

Fine-needle aspiration – of any palpable cervical lymph node; ±

Bronchoscopy – in high oesophageal tumours or if hoarseness or haemoptysis is present.

Chromoendoscopy (use of dyes), high-resolution endoscopy, spectroscopy, narrow band imaging (optical filter technology that improves the visibility of blood vessels) and autofluorescence (exploits the natural emission of light by biological tissues) are other modalities being investigated.

Staging

T category Depth of infiltration N category Regional lymph nodes
Tis Carcinoma in situ NX Nodes cannot be assessed
T1 Invasion of lamina propria/submucosa N0 No node spread
T2 Invasion of muscularis propria N1 Regional node metastases
T3 Invasion of adventitia M0 No distant spread
T4 Invasion of adjacent structures M1 Distant metastases

Management

Primary treatment modalities include surgery alone or with chemotherapy or radiation therapy Options should be selected after discussion with the patient, following a multidisciplinary meeting to consider staging, nutritional status and comorbidities.

Surgery

Antibiotic and antithrombotic prophylaxis should be instituted.

Endoscopic mucosal resection and submucosal dissection is an option for patients with early oesophageal cancer.

Endoscopy is frequently combined with other modalities Ex: Photodynamic therapy (PDT). 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. In one series, five-year disease-specific survival was 76% in 56 treated with PDT as monotherapy.

Other techniques employed with endoscopy to treat early cancers include lasers, electrocoagulation, argon plasma coagulation (APC) and radiofrequency ablation.

Endoscopic resection can also be used for more advanced tumours when the patient is unwilling or unfit to undergo more invasive surgery.

Oesophagectomy is the treatment of choice for most advanced cancers. The approach may be either through the diaphragm (transhiatal) or transthoracic and there is no clear evidence to support one method over the other.

Minimally-invasive (endoscopic) oesophagectomy is also possible.

Abdominal lymphadenectomy is beneficial in both SCC and AC. Mediastinal lymphadenectomy is of benefit in SCC but in AC the evidence base is less supportive.

Chemoradiotherapy is recommended for localised SCC of the proximal oesophagus. More distally, surgery may also be required.

Pre-operative chemoradiotherapy is recommended for AC. Pre-operative radiotherapy alone is of no benefit but chemotherapy before surgery improves survival.

Palliation

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, brachytherapy, chemotherapy, electrocautery or plasma/laser ablation may be of use (primarily in reducing tumour bulk and bleeding). Photodynamic therapy may also be used for palliation in advanced disease.

Trastuzumab in combination with cisplatin/fluoropyrimidine should be considered for patients with HER2-positive oesophago-gastric junctional AC.

Stenting is a first-line option to assist swallowing.

Nutritional status may be maintained by the use of liquid feeds, enteral nutrition or percutaneous endoscopic gastrotomy (PEG) tubes.

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

The Outlook

The patient’s pre-operative status, comorbidity and presence or absence of metastases are strong predictors of outcome. The prognosis for oesophageal carcinoma varies depending on the stage at presentation. The overall five-year survival rate is 20-25% for all stages. Not surprisingly, lymph node involvement equates with a poorer prognosis. The survival rate for AC and SCC are the same.

A study of 1,085 patients who underwent oesophagectomy showed a 4% operative mortality rate and a 23% survival rate. For patients who had pre-operative chemoradiotherapy, the prognosis improved to 48%.

Obviation

Reducing risk factors (obesity, smoking and alcohol) should help.

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