Tumours of the oesophagus

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Benign tumours of the oesophagus

Benign tumours of the oesophagus account for less than 1% of all oesophageal neoplasms. Leiomyomas are the most common; rarer entities include papillomas, fibrovascular polyps, granular cell tumours, adenomas, haemangiomas, neurofibromas, and lipomas.

Leiomyomas are smooth-muscle tumours arising in the oesophageal wall. They are usually solitary, well encapsulated with an intact overlying mucosa, and grow slowly. Most small (>5 cm) leiomyomas are asymptomatic and are incidental finding on barium study (see Barium contrast study showing the typical features of a leiomyoma of the oesophagus with a smooth semilunar defect in the contour of the oesophageal lumen and an intact mucosa, clear borders and a sharp angle between the tumour and the normal wall.). Diagnosis is made from the typical appearance on imaging, and endoscopy reveals intact mucosa. Sometimes leiomyomas can grow as an annular lesion producing dysphagia. There is no good evidence that they undergo malignant transformation to leiomyosarcoma.

Barium contrast study showing the typical features of a leiomyoma of the oesophagus with a smooth semilunar defect in the contour of the oesophageal lumen and an intact mucosa, clear borders and a sharp angle between the tumour and the normal wall.

Small, asymptomatic leiomyomas can be observed. Surgical removal is warranted for symptomatic or large leiomyomas (<5 cm). Simple enucleation is performed. Oesophageal resection is occasionally necessary for large or annular tumours.

Malignant tumours of the oesophagus

Epidemiology

Oesophageal cancer is the ninth most common cancer and the sixth most frequent cause of cancer death worldwide. Squamous cell cancer is the most common. There is marked geographical variation in the incidence of oesophageal cancer. Countries in the so-called ‘Asian oesophageal cancer belt’, which stretches from eastern Turkey and east of the Caspian Sea through northern Iran, northern Afghanistan and southern areas of the former Soviet Union, such as Turkmenistan, Uzbekistan and Tajikistan, to northern China and India, have high incidence rates. The disease is also common in the Transkei province of South Africa, and Kenya. In high incidence areas, the occurrence of oesophageal cancer is 50- to 100-fold higher than in the rest of the world, for instance the incidence rate is over 160 per 100 000 population in Henan Province of China and is only 2 to 3 per 100 000 population in North America, Australia, and most areas of Europe.

Smoking and alcohol intake are the main aetiological agents, though in certain areas, other dietary factors are implicated (see Table 19, “Factors associated with pathogenesis of oesophageal cancer”). Patients with other aerodigestive malignancies have a 5–8% risk of developing synchronous or metachronous oesophageal squamous tumours, probably because of exposure to the same environmental carcinogens and the phenomenon of ‘field cancerization’.

Table 19. Factors associated with pathogenesis of oesophageal cancer
Environmental factors Specific conditions * Predisposes to squamous cell cancers.
† Predisposes to adenocarcinomas.
Smoking History of aerodigestive tract malignancy*
Alcohol consumption Achalasia*
Hot beverages* Lye corrosive stricture*
N-nitroso compounds* Plummer vinson (paterson kelley) syndrome*
Betel nut chewing*
Deficiencies of*: Tylosis
Green vegetables Barrett's oesophagus†
Vitamins A, C and E
Niacin
Riboflavin
Beta-carotene
Zinc
Molybdenum
History of radiation to mediastinum (e.g. ca breast)
Low socio-economic class*
Obesity†
Fungal toxin or viral infection

In western countries, the most striking change in epidemiology in the past three decades was the increase in incidence of adenocarcinomas of the lower oesophagus and gastric cardia. In the United States, the rate of adenocarcinoma has risen by more than 350% since 1970, surpassing squamous cell cancer around 1990. This shift in cell type is not apparent in Asian or African countries. The phenomenon is believed to be related to gastro-oesophageal reflux disease, obesity, and the pre-malignant condition of Barrett's oesophagus. Barrett's oesophagus is a condition in which the squamous epithelium of the distal oesophagus is replaced by a columnar epithelium characterized by the presence of specialized intestinal metaplasia. Diagnosis used to rely on endoscopic finding of a length of columnar epithelium of more than 3 cm, but current definition centres on histological identification rather than absolute length. The prevalence of adenocarcinoma in patients with Barrett's oesophagus averages about 13%, equivalent to at least a 30-fold increase in the risk of cancer compared to the general population. The Barrett's epithelium progresses through low-grade to high-grade dysplasia to invasive cancer. It is also suggested that the high prevalence of Helicobacter pylori infection in the East has a protective role against reflux, and hence Barrett's oesophagus and cancer. This hypothesis remains controversial.

Surgical pathology

Squamous cell cancers and adenocarcinomas constitute the majority, together accounting for over 95% of all cancers. Other tumours, all of which are uncommon, include muco-epidermoid carcinoma, small cell carcinoma, adenoid cystic carcinoma, adenosquamous carcinoma, basaloid squamous cell carcinoma, sarcomas, lymphoma and melanoma. In countries where increase in adenocarcinomas is not observed, the majority of squamous cell cancers are located in the middle or lower portions of the oesophagus, while adenocarcinomas are mostly gastric cardia in position. This is in contrast to theWest, where most adenocarcinomas are found in the lower oesophagus and gastric cardia.

In patients with Barrett's oesophagus, the premalignant dysplastic stages allow endoscopic surveillance to be carried out; however the optimal interval, benefits and cost-effectiveness are uncertain since most patients with oesophageal carcinoma present without a history of Barrett's oesophagus. Endoscopic ablation of Barrett's mucosa by laser, photodynamic therapy or other means followed by intensive acid suppressive therapy or fundoplication has been advocated in order to revert the epithelium to a squamous type. Whether such strategies can halt the progression to cancer is still under investigation.

The oesophagus has a rich plexus of intramural and submucosal lymphatics. Lymphatic spread tends to spread early and longitudinally, even to the neck and abdomen. Multi-centric tumours and submucosal spread should be searched for when a diagnosis of oesophageal cancer is made.

Clinical features

Oesophageal tumours are generally described with respect to their location in the oesophagus. The cervical oesophagus extends from the cricopharyngeus muscle at C6 level to the thoracic inlet (approximately 18 cm from the upper incisor teeth). The upper third of the intrathoracic oesophagus extends from the thoracic inlet to the tracheal bifurcation (24 cm), the middle third includes the proximal half of the oesophagus between the tracheal bifurcation to the diaphragmatic hiatus, the lower third being the distal half of this segment, and a short segment of abdominal oesophagus remains. The junction between the middle and lower thirds corresponds to approximately 32 cm from the upper incisor teeth, and the gastro-oesophageal junction ends at 40 cm.

Increasing incidence of adenocarcinomas of the lower oesophagus and cardia has prompted a classification of adenocarcinomas around the gastrooesophageal junction, which includes adenocarcinomas found within a distance of 5 cm proximal and distal to the gastro-oesophageal junction (Classification of adenocarcinomas around the gastro-oesophageal junction.). Depending on the bulk and epicentre of the tumours, type I tumours are lower oesophageal (many are Barrett's) adenocarcinomas, type II centres at the cardia, and type III are subcardiac cancers. It is suggested that the three types differ in pathologic and clinical features.

Classification of adenocarcinomas around the gastro-oesophageal junction.

Most patients are more than 50 years of age, with a male predominance. Dysphagia is the most common symptom, and is rapid in onset, progressing from difficulty in swallowing solid food and later to liquid within a matter of weeks. Symptom of dysphagia is usually not felt until the tumour is advanced. The site of the ‘hold-up’ sensation has only a modest correspondence to the location of the tumour; it is usually located above, but not below, the actual site of obstruction.

Regurgitation, loss of weight, and substernal pain or discomfort are common. Hoarseness signifies recurrent laryngeal nerve palsy from direct tumour infiltration or from lymphatic spread and is thus a poor prognostic sign. Coughing or choking on eating may be due to aspiration, predisposed by the presence of vocal cord palsy if present, or the development of an oesophageal-respiratory fistula. Squamous cell cancers of the oesophagus rarely bleed. Patients with dysphagia and also evidence of gastrointestinal bleeding are more likely to have adenocarcinomas of the gastrooesophageal junction. Exsanguinating haemorrhage from an oesophageal-aortic fistula is rare. Cervical lymph nodes should be searched for. Haematogenous spread to the lungs, liver, bones and other visceral organs, as well as hypercalcaemia from bone metastases or as a paraneoplastic phenomenon, are not infrequent.

Investigations

A barium swallow identifies the location and length of oesophageal narrowing, mucosal irregularity, dilatation of the proximal oesophagus, and the ‘shouldering’ impression made by the upper border of the tumour (see Barium contrast study showing the typical features of a leiomyoma of the oesophagus with a smooth semilunar defect in the contour of the oesophageal lumen and an intact mucosa, clear borders and a sharp angle between the tumour and the normal wall.). Features suggestive of advanced disease include deformity of the oesophageal axis, and sinuses that extend into the mediastinum or frank fistulation into the respiratory track. Most tumours present at an advanced stage, so diagnosis is not problematic. In earlier lesions, biopsies together with brush cytology improve the diagnostic accuracy. The application of Lugol's iodine stain helps direct biopsies to dysplastic or early mucosal lesions, since only normal oesophageal mucosa is stained brown, and the interested areas will remain unstained.

Barium contrast study showing the typical features of a leiomyoma of the oesophagus with a smooth semilunar defect in the contour of the oesophageal lumen and an intact mucosa, clear borders and a sharp angle between the tumour and the normal wall.

Staging methods

Accurate pre-operative staging allows selection of the most appropriate treatment. Current TNM staging classifications are shown in Table 20, “Stage groupings for oesophageal cancer”. Bronchoscopic examination is mandatory for tumours in close proximity to the tracheo-bronchial tree. Direct tumour infiltration precludes surgical resection. Vocal cord paralysis suggests recurrent laryngeal nerve involvement. A pan-endoscopy also serves to examine the rest of the upper aerodigestive tract to look for other synchronous tumours. The use of computed tomography (CT) scans to assess the depth of oesophageal wall penetration, the degree of contiguous mediastinal structures and regional lymph node involvement are not sufficiently accurate except in overtly advanced cases. The obliteration of a ‘fat plane’ around the oesophagus may suggest extra-oesophageal infiltration although the paucity of fat especially in patients who have substantial weight loss makes this inaccurate. CT scans are more useful to detect distant metastases.

Table 20. Stage groupings for oesophageal cancer
T: Primary tumour
Tx Tumour cannot be assessed
Tis In situ carcinoma
T1 Tumour invading lamina propria or the submucosa, does not breach submucosa
T2 Tumour invading into but not beyond the muscularis propria
T3 Tumour invades the adventitia but not the adjacent structure
T4 Tumour invades the adjacent structure
N: Regional lymph nodes*
NX Regional nodal status cannot be assessed
N0 No regional lymph node involvement
N1 Regional lymph node involved
M: Distant metastases
Mx Distant metastases cannot be assessed
M0 No distant metastasis
M1a Upper thoracic oesophagus with metastases to cervical nodes
Lower thoracic oesophagus with metastases to coeliac nodes
M1b Upper thoracic oesophagus with metastases to other non-regional nodes or other distant sites
Lower thoracic oesophagus with metastases to other non-regional nodes or other distant sites
Middle thoracic oesophagus with metastases to cervical, coeliac, other non-regional nodes or other distant sites
Stage T N M * For cervical oesophageal cancer, regional nodes are the cervical nodes. For intrathoracic cancers, the mediastinal and perigastric nodes (excluding coeliac nodes), are considered regional.
Stage 0 Tis N0 M0
Stage I T1 N0 M0
Stage IIa T2 N0 M0
T3 N0 M0
Stage IIb T1 N1 M0
T2 N1 M0
Stage III T3 N1 M0
T4 N0#x2013;N1 M0
Stage IVa Any T Any N M1a
Stage IVb Any T Any N M1b

Endoscopic ultrasonography (EUS) is best in T-stage and regional nodal (N) staging, the accuracy of determining T-stage ranges between 85% and 90%, while N-staging accuracy approximates 70% to 90%. Recent advances also allow EUS-guided fine needle aspiration cytology of suspicious lymph nodes to be carried out.

Positron-emission tomography (PET) with 18-F-fluoro-deoxy-D-glucose (FDG) is increasingly used, and is of particular value in picking up distant nodal or systemic metastases. Sensitivity, specificity and accuracy rates for the detection of distant metastases of 88%, 93% and 91% respectively are reported, but localregional staging of N1 disease seems inferior to EUS. Laparoscopic and thoracoscopic staging are practised in selected centres. The former may be useful for lower oesophageal or cardiac tumours, the latter is more invasive, and its use is unlikely to gain widespread support.

Principles of treatment

A simplied therapeutic algorithm is shown in Management protocol for patients with oesophageal cancer.. Patients with obvious disseminated disease should be palliated by non-surgical means. Those with early disease generally do well with surgical resection, provided an R0 resection (curative procedure with macroscopic and microscopic clear margins) can be performed. In patients with local-regional advanced disease, upfront combined treatments including chemotherapy and radiotherapy are often used, and subsequent surgical resection depending on response. There is, however, no clear evidence that this gives superior result to surgical resection alone.

Management protocol for patients with oesophageal cancer.

Operative treatment

Contraindications against surgical resection include presence of distal visceral or nodal metastases, direct infiltration of the tracheo-bronchial tree or aorta, although sometimes accurate diagnosis of the latter may be established pre-operatively. The indication for palliative surgery has lessened, while other effective options are available.

Potential surgical candidates should have a careful risk assessment especially with regards to cardiopulmonary status. Smoking should be stopped and active chest physiotherapy instituted. Pre-operative enteral nutrition or parenteral nutrition may be beneficial.

For tumours of the middle and lower third of the oesophagus, the most often performed operation is the Lewis-Tanner (Ivor Lewis) operation (see A Lewis-Tanner (Ivor Lewis) oesophagectomy with intra-thoracic esophago-gastrostomy.). The stomach, the blood supply of which is based on the right gastric and right gastroepiploic vessels, is mobilised via laparotomy. A pyloroplasty or pyloromyotomy is performed to enhance gastric drainage. The oesophagus is then resected through a right thoracotomy. The stomach is delivered up into the thorax via the diaphragmatic hiatus to anastomose with the divided oesophagus near the apex of the thoracic cavity.

A Lewis-Tanner (Ivor Lewis) oesophagectomy with intra-thoracic esophago-gastrostomy.

In type II and III tumours around the gastrooesophageal junction, an extended total gastrectomy with a distal oesophageal resection is often performed, although some surgeons advocate a proximal gastric and distal oesophageal resection. Both can be accomplished via the abdomen or with an additional thoracotomy.

In tumours of the upper thoracic oesophagus, oesophagectomy can be performed through a right thoracotomy, then by simultaneous left cervical and abdominal incisions the stomach can be prepared and delivered up to the neck for anastomosis (McKeown's procedure; see A three-phase oesophagectomy. The colon is placed in the retrosternal route in this example with anastomosis in the neck.).

A three-phase oesophagectomy. The colon is placed in the retrosternal route in this example with anastomosis in the neck.

In transhiatal oesophagectomy, the oesophagus is ‘shelled’ out by the surgeon's hand introduced in the posterior mediastinum via the diaphragmatic hiatus and the neck without a thoracotomy. This partly blind procedure may lead to injury to mediastinal structures, such as the membranous trachea, and has also been criticised as an inadequate cancer operation. In experienced hands however, it is safe, and its proponents claim similar survival to the transthoracic approach. Various minimal-access methods including combinations of thoracoscopy, laparoscopy and mediastinostomy have been attempted. The myriad of surgical methods implies a lack of consensus to which is the best. Proof of their superiority over conventional techniques is not forthcoming.

Most surgeons perform lymphadenectomy of the upper abdomen and mediastinum (two-field dissection). Some surgeons, especially in Japan, advocate the addition of bilateral neck dissection (three-field dissection) because of the high incidence of positive cervical lymph nodes found when neck dissection is carried out (up to 30%), and better cure rate is claimed. Again the optimal extent of lymph node dissection is a controversial subject.

The stomach is most commonly used for oesophageal substitution. In patients with previous gastric surgery, other substitutes like the colon or jejunum can be used. In cases where the substitute is brought to the neck for anastomosis, the posterior mediastinum (orthotopic), retrosternal route or subcutaneous space are alternatives.

Tumours of the cervical oesophagus require the resection of the larynx and pharynx, and the stomach is usually used to restore continuity (pharyngo-laryngo-oesophagectomy). A terminal tracheostome is performed and alternative voice rehabilitation is required. For tumours limited to the postcricoid region, resection need not involve the thoracic oesophagus and a free jejunal graft can be placed in the neck to restore intestinal continuity after pharyngo-laryngectomy. For these tumours, in order to preserve the larynx, often non-operative treatment such as chemoradiation therapy is used as an alternative to surgical resection.

Complications of surgery

Pulmonary complications are the most common, followed by cardiac problems (see Table 21, “Complications after oesophagectomy”). Cessation of smoking, peri-operative chest physiotherapy, care to avoid fluid overload, and regular bronchoscopic clearance of retained sputum are beneficial. Early tracheostomy in patients who have poor cough effort, especially in those who have vocal cord paralysis, is invaluable for facilitation of sputum suction. Atrial arrhythmia is also common; most are benign and are controlled with appropriate medication. It is important, however, to look for an underlying cause since it may be indicative of pulmonary or surgical septic pathologies.

Table 21. Complications after oesophagectomy
Note: Surgical complications are technique- and operator-dependent, thus incidences can vary.
* Relatively common occurrence.
† Should be all uncommon.
Medical

Surgical

  • Intra-operative or post-operative haemorrhage
  • Tracheo-bronchial tree injury
  • Recurrent laryngeal nerve injury
  • Anastomotic leakage
  • Gangrene of conduit
  • Intra-thoracic gastric outlet obstruction or gastric stasis
  • Herniation of bowel through diaphragmatic hiatus
  • Chylothorax
  • Empyema
  • Wound infection

Cardiac

  • Atrial arrhythmia*
  • Myocardial infarction
  • Cardiac failure

Pulmonary

  • Atelectesis*
  • Pneumothorax
  • Bronchopneumonia with or without aspiration*
  • Sputum retention*
  • Pleural effusion*
  • Pulmonary embolism

Other medical†

  • Renal failure
  • Hepatic failure
  • Stroke

Surgical complications are mostly related to faulty techniques. Anastomotic leak, which was once a common event, should now be rare in specialised centres (<5%). Treatment principle involves adequate drainage, antibiotics and nutritional support. Convincing evidence exists that demonstrates a hospital-volume and surgeon-volume outcome relationship with complex surgery like oesophagectomy. Mortality rate in dedicated centres is below 5%.

Non-operative treatments

Chemotherapy and radiotherapy

In the past, external-beam radiation has been used as the main alternative to surgery. Relief of dysphagia is however less effective, and radiation strictures may develop. Chemoradiation therapy gives superior result to radiation alone in the treatment of oesophageal cancer, both in terms of response rate, local control, and long-term survival. Radiotherapy alone has thus mostly a palliative role in patients who cannot tolerate the addition of chemotherapy. Brachytherapy, or intraluminal radiotherapy, whereby radioactivity is delivered in close proximity to the tumour via a tube placed inside the oesophagus, can also produce good palliation.

As neo-adjuvant or adjuvant therapy with surgery, neither radiotherapy and/or chemotherapy has been conclusively demonstrated to improve overall survival compared to surgical resection alone. Only patients with good response tend to benefit. All these treatments have potential disadvantages, such as prolonging treatment time and toxicities and increasing perioperative morbidity.

Most commonly used conventional drugs used for oesophageal cancer are cisplatin and flurouracil. New drugs are being explored. Search for reliable markers for prediction of response to chemoradiation is important, so that potentially toxic treatments are not given to those unlikely to respond. Various serological, histological, and molecular markers are being examined; metabolic imaging by PET scan, with its measurement of ‘tumour activity’, shows some promise in predicting response early in the course of treatment.

Other treatment options

For early mucosal lesions, endoscopic mucosectomy can be performed. The mucosal cancer is ‘raised’ by injecting saline in the submucosal plane; it is then snared by an electrocautery loop as in polypectomy.

Placement of a prosthetic tube across the tumour stenosis may be indicated in patients not otherwise suitable for other treatment to palliate the symptom of dysphagia. Traditional tubes placed by laparotomy (e.g. Celestin tube, Mousseau-Barbin tube) or oesophagoscopy under sedation (e.g. Atkinson tube, Souttar tube) are now rarely used since they have been superseded by a variety of self-expanding metallic stents (see A self-expanding metallic oesophageal stent in situ.). Placement of these stents is less traumatic and immediate complications are less.

A self-expanding metallic oesophageal stent in situ.

Laser therapy (Neodymium:yttrium aluminium garnet [Nd:YAG] laser) vaporises the tumour to restore luminal patency. Recannulation often requires repeated treatment sessions, and the effect is temporary.

Other less commonly used non-surgical options include injection of the tumour with alcohol or chemotherapeutic agents, photodynamic therapy, and use of a bicap heater probe. The choice of therapy depends on availability, cost and consideration of efficacy.

Prognosis

Overall prognosis remains poor with oesophageal cancer because of late disease presentation. At the authors' institution, in patients with squamous cell carcinomas and who undergo surgical resection alone, 5-year survival of patients with stage I, II, III and IV disease are 83%, 32%, 13% and 7% respectively. The figures were 31% and 8% for R0 and R1/2 resections, and were 35% and 15% for those with node negative and positive disease respectively. In large Western series, it has been suggested that overall survival in patients with adenocarcinomas is better that those with squamous cell cancers.

Surgery remains the mainstay treatment for oesophageal cancer, offering the most complete and lasting restoration of swallowing ability and a chance of cure. In specialised centres oesophageal surgery can be performed safely on a wide spectrum of patients. For centres with less experience, more restrictive patient selection is essential. How to integrate various combined multimodality treatment programmes of chemotherapy and radiotherapy deserves more study, and their impact on long-term prognosis should be evaluated in wellconducted clinical trials.
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