Article about diseases of the oesophagus - technical
Defective conduit function of the oesophagus readily induces clinical symptoms and may have serious effects on nutrition and the lungs, the latter resulting from aspiration of gastro-oeophageal contents. Oesophageal pain and dysphagia caused by benign or malignant diseases of the muscular layer or epithelium are often disabling.
The oesophagus is exposed to numerous hostile environments including carcinogens in food or those derived from tobacco, betal nuts and other ingested sources. Reflux disease may be associated with exposure to corrosive upper gastrointestinal secretions, the chronic effects of which are also associated with malignant disease — adenocarcinoma — as well as stricture formation related to the action of pepsin.
Diagnosis and treatment of suspected oesophageal disease has been enhanced by the introduction of endoscopic techniques, but in some circumstances radiological investigations and dynamic studies of oesophageal motor function using manometry provide essential guidance for diagnosis of achalasia, oesophageal spasm and motor disorders related to systemic diseases such as scleroderma.
Direct visualization of the oesophagus combined with biopsy offers immediate benefit for the diagnosis of mucosal diseases such as: (1) infections due to candida and herpes simplex virus; (2) benign and malignant strictures; (3) bleeding lesions – including varices.
Particular oesophageal disorders
Gastro-oesophageal reflux disease is by far the most common oesophageal disorder and usually arises from excessive exposure of the distal oesophagus to gastric contents (acid and/or bile). Presentation can be with obviously digestive symptoms (e.g. heartburn, dyspepsia) or with extra-oesophageal manifestations (e.g. hoarseness, cough). The history is pivotal for diagnosis because of the extremely high prevalence of reflux-induced symptoms and the lack of a definitive, inexpensive diagnostic test. A trial of acid-suppression therapy can be used as an aid to diagnosis, with endoscopy the first choice test when investigation is required. Proton pump inhibitors are the mainstay of treatment.
Gastro-oesophageal reflux disease may be complicated in 5-10% of cases by Barrett’s oesophagus, a columnar epithelial metaplasia which predisposes to the development of adenocarcinoma and hence requires endoscopic surveillance. Limited surgical procedures to excise pre-malignant tissue as well as laser ablative methods are currently being evaluated.
Oesophageal adenocarcinoma and tumours of the gastro-oesophageal junction usually occur in association with Barrett’s oesophagus. Inexorable progression of dysphagia to solids, and eventually to liquids, over several weeks is the almost universal presentation. Staging using the TNM system is essential for all patients fit for radical therapy. Surgery is the treatment of choice in early stage disease. Prognosis is dismal except where screening programmes identify early, asymptomatic cases: only about 25% of those presenting with symptoms are potentially curable by surgery, and the overall 5-year survival rate is about 13%.
Primary oesophageal motor disorders include idiopathic achalasia and achalasia-like states and are characterized by increased lower oesophageal sphincter (LOS) tone, absence of LOS relaxation with swallowing, and impairment of peristalsis of the oesophageal body. Presentation is typically with dysphagia for solids. Oesophageal manometry is the only sensitive method for diagnosis. Treatment is with (1) agents that relax the lower oesophageal sphincter, (2) mechanical disruption of the sphincter, and (3) pharmacological poisoning of the remaining excitatory nerves to the sphincter with botulinum toxin. Oesophageal motor disorders secondary to systemic disease include systemic sclerosis.
Diffuse oesophageal spasm presents with episodic chest pain and/or dysphagia resulting from abnormal contractions of the distal half of the oesophageal body in the absence of any precipitating structural stenosis. The diagnosis is usually made on the basis of the history and the exclusion of other problems. There is no specific therapy: reassurance is the most important management since the intensity and nature of symptoms often gives rise to great concern.
Numerous miscellaneous conditions affect the oesophagus, including motor disorders related to neurodegenerative diseases, amyloidosis, oesophageal rupture (either spontaneous, as in Boerhaave’s syndrome or, as a complication of interventions such as dilatation procedures for benign peptic strictures).
The oesophagus is responsible for transporting food to the stomach without compromising the safety of the airway. Imprecise muscle coordination of the oropharynx and the oesophageal body can have serious consequences such as aspiration pneumonia and malnutrition. Diseases of the oesophagus generally present with symptoms of pain or dysphagia either alone or in combination (odynophagia). True oesophageal dysphagia should be distinguished from oropharyngeal dysphagia, an abnormality of transfer of food from the mouth to the oeosphagus, by a careful history. Other symptoms and signs of oesophageal disease include weight loss, anaemia, cough, hoarse voice, and breathlessness secondary to aspiration pneumonia. The most common oesophageal disorder is gastro-oesophageal reflux disease which should be taken seriously because of its profound impact on quality of life in some people and since it can be a precursor to oesophageal adenocarcinoma. The diagnosis of oesophageal disease may generally be determined by a thorough history and a small number of focused investigations outlined below.
Diagnosis and treatment of suspected oesophageal disease has been enhanced by the introduction of endoscopic techniques, but in some circumstances radiological investigations and dynamic studies of oesophageal motor function using manometry provide essential guidance for diagnosis of achalasia, oesophageal spasm, and motor disorders related to systemic diseases such as scleroderma.
An oesophagogastroduodenoscopy is usually the first investigation of choice to determine whether there is a mechanical cause for the symptoms and whether there is any evidence of inflammation or mucosal damage. Direct visualization of the oesophagus combined with biopsy as appropriate, offers immediate benefit for the diagnosis of mucosal diseases such as: (1) infections due to candida and herpes simplex virus; (2) benign and malignant strictures; (3) bleeding lesions, including varices. Although the endoscopic appearances may be suggestive of a motility disorder this is not the investigation of choice for assessing oesophageal function. Endoscopic technology is advancing rapidly and enhanced magnification coupled with permutations in the parts of the light spectrum used for image processing (e.g. narrow band imaging) permit a more detailed analysis of the mucosa in real time. It is hoped that these technologies will aid diagnosis, e.g. of dysplasia.
Endoscopic ultrasound is an important staging investigation for oesophageal cancer (see below) and also has a role in characterizing submucosal lesions.
A plain cervical and chest radiograph should be taken in cases where oesophageal perforation is suspected. The barium or gastrograffin swallow has largely been superseded by endoscopy for the diagnosis of structural abnormalities; however, it can be a useful guide prior to interventions such as endoscopic stent insertion and to evaluate conduit functioning postoperatively. Useful information can also be obtained about the motor function of the pharynx and oesophagus by videotaping the images and analysing, in slow-motion replay, repeated tests of standardized stimuli such as bread or barium tablets. Optimal results from radiology are achieved when there is a partnership between a clinician and a radiologist who both have a special interest in oesophageal motor disorders, so that the examination technique can then be tailored accordingly. CT scanning and positron emission tomography, increasingly as part of a combined procedure (CT-PET), are part of the staging investigations for oesophageal cancer (see below). MRI has a limited role for oesophageal disease.
Oesophageal function testing
Techniques are now available for the precise measurement of oesophageal motor function. These include oesophageal manometry, intraluminal impedance monitoring, video fluoroscopy, and high-resolution oesophageal manometry with isocontour mapping. Together these techniques build a dynamic picture of the physiological sequence of events and the effectiveness of contraction which can be compared with resultant functional outcome. These tests may also have a clinical role for explaining symptoms to patients even in the absence of therapy.
Oesophageal manometry provides the most direct indication of patterns of oesophageal motor function. It is most helpful in the diagnosis of dysphagia, after exclusion of fixed, structural defects. Manometry may also be useful to confirm the placement of intraluminal devices such as pH probes and to assess pre- and postoperative results following surgery for achalasia or reflux. It may be performed as a stationary test with a liquid swallow or as a prolonged, ambulatory 24-h manometry. This is conventionally performed with a transnasal catheter although, more recently, wireless devices have become available. To determine the association between reflux episodes and symptoms pH catheters can be used to provide either a stationary or ambulatory recording. Again wireless devices are increasingly used. Ambulatory monitoring is particularly useful to determine the association between symptoms and episodes of acid reflux in a minority of patients in whom the origin of troublesome symptoms is unclear. This test is generally performed off medication but may occasionally be useful to assess response to therapy.
Radionuclide measurement of oesophageal transit
Computerized scintigraphic analysis of the movement of swallowed radiolabelled boluses can give quantitative information about the patterns of movement of material down the oesophagus. However, its poor spatial resolution makes it an inadequate method for the display of oesophageal anatomy. If structural abnormalities have been adequately excluded, slow or interrupted transit suggests abnormal motility, although patterns of transit are usually nonspecific.
Continued in these articles:
- Gastro-oesophageal reflux disease - technical article
- Gastro-oesophageal reflux disease - not technical
- Oesophageal Cancer
Oesophageal cancer is also covered in this article further below (with different content).
Primary oesophageal motor disorders
Idiopathic achalasia and achalasia-like states
These disorders are characterized by increased lower oesophageal sphincter tone, absence of lower oesophageal sphincter relaxation with swallowing, and impairment of peristalsis of the oesophageal body. Idiopathic achalasia, which was first described over 300 years ago, accounts for more than 95% of cases and has an annual incidence of approximately 1 to 2 per 100 000. It affects all ages, but is diagnosed most often in early to mid adult life. Primary familial achalasia, which is genetically transmitted accounts for less than 1% of cases.
There are a number of causes of secondary or pseudoachalasia. The most common are due to malignant infiltration of the gastro-oesophageal junction which has been reported with carcinoma of the stomach, oesophagus, lung, pancreas, and prostate, and with lymphoma. It may also be a manifestation of paraneoplastic neural dysfunction. Chagas’ disease is an important cause worldwide and can sometimes accompany the intestinal pseudoobstructive syndrome. There are a number of other secondary causes including oesophageal amyloidosis and sarcoidosis. Achalasia can also occur in associated with neurodegenerative diseases including Parkinson’s disease and cerebellar ataxia.
Impairment of inhibitory neural control of the distal oesophagus is the universal abnormality. The clearest evidence is degeneration of myenteric inhibitory neurons which, in the early stages, is associated with an inflammatory response. There is increasing evidence that the resulting nitric oxide deficiency may be causative.
Dysphagia with solids is almost universal, but the symptoms may extend to include liquids and regurgitation is also prominent. The regurgitated material tastes bland because it never enters the stomach. Cramping chest pain occurs in some patients during an early hypercontracting phase of the disorder. Weight loss is seen in patients with disabling dysphagia. The course of symptoms over time is variable in contrast to the progressive symptoms in patients with a malignant cause. Over a prolonged period of a hypertonic lower oesophageal sphincter, continuing oesophageal dilatation may result with increasing regurgitation. When this occurs, respiratory problems secondary to aspiration can become a major feature.
Idiopathic achalasia is diagnosed on average 2 years after its first presentation. Oesophageal manometry is the only sensitive method for demonstration of the characteristic motor dysfunction. It is not unusual for manometry to be diagnostic of achalasia even though barium studies have been judged to be normal. In advanced disease a barium swallow may reveal gross oesophageal dilatation with a gastro-oesophageal junction that tapers smoothly to a closed sphincter, with occasional spurts of flow into the stomach.
As noted above, idiopathic achalasia and achalasia-like states should be distinguished from constriction of the gastro-oesophageal junction by an infiltrating or encasing malignancy at the cardia. This can be difficult to ascertain with certainty. If there are any grounds to suspect malignancy then an endoscopy should be performed including multiple biopsies from the gastro-oesophageal junction. CT scanning may also be helpful in these circumstances.
There are three potential approaches to treatment: drug therapy with agents that relax the lower oesophageal sphincter, mechanical disruption of the sphincter by either pneumatic dilatation or surgical myotomy, and pharmacological poisoning of the remaining excitatory nerves to the sphincter with botulinum toxin. The results of reduction of lower oesophageal sphincter pressure with drugs such as calcium antagonists and β-adrenergic agonists compare poorly with mechanical techniques.
Oesophagomyotomy can now be performed as a laparoscopic or thoracoscopic procedure. It is highly effective but is associated with a 5 to 10% risk of troublesome gastro-oesophageal reflux. This risk can be minimized by the incorporation of an antireflux procedure.
Balloon dilatation is an attractive approach because of its simplicity and low cost, but it often needs to be repeated and may fail in up to 40% of patients, especially those who are young. It also carries a risk of perforation of about 5%. With the development of minimally invasive surgery for oesophagomyotomy, balloon dilatation is generally reserved for older patients who have other medical problems that increase the risks of surgery.
Endoscopic injection of the sphincter with botulinum toxin acts on residual excitatory nerves, thereby lowering sphincter pressure. Short-term results are comparable to those of pneumatic dilatation but the procedure usually has to be repeated within 1 to 2 years. The toxin is also relatively expensive. It is a simple, low-risk procedure and most applicable to patients with significant coexisting morbidity which renders them unfit for dilatation or myotomy.
When oesophageal dilatation is present, prompt treatment is indicated because of the morbidity and poor therapeutic outcome associated with gross oesophageal dilatation.
Results are excellent if effective treatment is applied before the development of major dilatation, despite the persistence of major physiological abnormalities. Achalasia carries a significantly increased risk for oesophageal malignancy (squamous cell and, more recently appreciated, adenocarinoma) up to three decades later. The prevalence ranges from 2 to 7% (or a standardized incidence ratio of around 10) in the most comprehensive reports. There is no apparent reduction of this risk with treatment. It is not usual practice to undertake surveillance for this condition.
Oesophageal motilty disorders - non-technical (similar content)
Diffuse oesophageal spasm
Episodic chest pain and/or dysphagia resulting from abnormal contractions of the distal half of the oesophageal body in the absence of any precipitating structural stenosis. There are no generally agreed criteria for diagnosis.
The aetiology of this disorder is poorly understood. Stress is an unlikely primary precipitant but may exacerbate the problem. Good prevalence data are lacking but it affects all age groups.
Virtually all patients have episodic, crushing central retrosternal pain which can be excruciating and may be misinterpreted as cardiac ischaemia. Intermittent dysphagia occurs in about two-thirds of patients and leads to temporary abandonment of eating until symptoms abate. Episodes of oesophageal obstruction usually last for approximately 30 min but can last for several hours. In most patients, symptomatic episodes occur less than once a month but in severe cases these may occur several times a week, or each time food intake is attempted.
Due to the intermittent nature of the problem investigations may be normal. Most frequently the diagnosis is made on the basis of the history and the exclusion of other problems that may mimic diffuse oesophageal spasm such as myocardial ischaemia and a Schatzki ring (see below). Oesophageal manometry may show intermittent, simultaneous, prolonged, and vigorous oesophageal contractions interspersed with normal swallow-induced peristalsis. Relaxation of the lower oesophageal sphincter is normal thus excluding achalasia as a cause. 24-h ambulatory manometry may improve diagnostic accuracy by increasing the likelihood of capturing symptomatic episodes.
Barium swallow may show trapping of contrast beads in the distal oesophagus—the ‘corkscrew oesophagus’—or sustained obliteration of the distal oesophageal lumen. This is not the investigation of choice.
There is no specific therapy. Smooth muscle relaxants such as nitrites, nitrates (given as sublingual spray), and calcium antagonists may reduce symptoms but their use is often limited by side effects. In many patients, reassurance is the most important management since the intensity and nature of symptoms gives rise to great concern. Opiate therapy is sometimes necessary. In the rare case of frequent, disabling spasm oesophagomyotomy can give good relief.
The major significance is impairment of quality of life and concern about life-threatening cardiac disease. There is no consistent progression over time. There are several reports of progression of diffuse oesophageal spasm to achalasia but in most of these it seems likely that achalasia was initially misdiagnosed as diffuse oesophageal spasm.
Hypertensive peristalsis or nutcracker oesophagus
This is defined purely by the manometric demonstration of primary peristaltic pressure waves in the oesophageal body that have peaks in excess of 250 mmHg in a symptomatic patient. There is preservation of the normal peristaltic pattern with a broad progression of the time of onset of the contraction wave in the oesophageal body.
It is not clear if this is a true motor disorder or whether it represents the upper end of a continuum of peristaltic wave amplitudes. It has been shown to vary over time within individuals. There are indications that psychological factors can influence peristaltic amplitude. A minority of patients with hypertensive peristalsis also experience episodes of diffuse oesophageal spasm, suggesting that their underlying dysfunction may be related and involve neural control mechanisms.
The only clinical significance of hypertensive peristalsis is its relationship to noncardiac chest pain. Hypertensive peristalsis alone does not produce dysphagia or derangement of oesophageal transit, because, by definition, peristalsis is preserved.
Treatment and prognosis
These are discussed in the section on noncardiac chest pain.
Nonspecific oesophageal motor disorders
There are likely to be several mechanisms involved. The intermittent occurrence of dysfunctions suggests that they are due to defective neural control.
Swallow-induced distal oesophageal body contraction waves with multiple peaks stand out from the other patterns not only functionally but also symptomatically. This pattern is loosely associated with the hypercontraction disorders of diffuse oesophageal spasm and hypertensive peristalsis, but sometimes does not appear to have any clinical significance. Hypocontraction dysfunctions, recently termed ‘ineffective’ peristalsis, are associated with defective triggering and progression of both primary and secondary peristalsis. Failure to develop a propagated pressure wave of sufficient strength to maintain closure of the oesophageal lumen leads to deranged oesophageal transit. This probably explains the association of these disorders with mild intermittent dysphagia which occurs characteristically with solids. The nonobstructive dysphagia and slow oesophageal acid clearance seen in gastro-oesophageal reflux disease are due to such dysfunction. Secondary oesophageal body peristalsis has not yet been widely evaluated, but it is probably an important cause of intermittent dysphagia, since, at least in patients with nonobstructive dysphagia and reflux disease, dysfunction of secondary peristalsis is substantially more common than primary peristaltic dysfunction. Oesophageal manometry with an adequate number of recording points in the oesophageal body is the only sensitive means for diagnosis.
In most cases patients seek reassurance and an explanation about the origin of their symptoms. Prokinetic agents may improve triggering and amplitude of peristaltic contractions and so, theoretically, of transit. Secondary peristaltic dysfunction may be more troublesome, but there is no good information on the effect of prokinetic or other drugs on this.
These dysfunctions do not remit spontaneously. Patients are often helped by the measures outlined in the section on general management of oesophageal dysphagia, which minimize the demands on oesophageal transport mechanisms and provide propulsive forces that substitute for oesophageal contractions.
Noncardiac chest pain
Implicit in this rather circuitous and negative label is the view that this pain has a cardiac-like quality, but there is no evidence for a cardiac origin. The oesophagus is the next most likely origin, but it is unlikely that all such pain arises from the oesophagus.
Evidence for triggering of pain by reflux or oesophageal motor dysfunction has been found in between one-fifth and one-half of patients evaluated. Oesophageal mucosal pain due to gastro-oesophageal reflux is the most common and helpful diagnosis. Frank oesophageal spasm associated with achalasia and diffuse oesophageal spasm is an unusual but convincing cause of noncardiac chest pain. In the majority of patients, most episodes of pain occur independently of reflux and any motor abnormality, although many of these patients have nonspecific oesophageal motor disorders or hypertensive peristalsis (see above). Sustained contraction of the longitudinal muscle has been identified by prolonged intraluminal ultrasonography in association with a high proportion of episodes of pain. Nevertheless, in many patients noncardiac chest pain appears to be a primary oesophageal hypersensitivity disorder and any motor disorder may be an epiphenomenon. Recent work to understand the neurophysiological basis for the hypersensitivity suggests that there may be distinct phenotypic subclasses of disease based on enhanced afferent transmission defects vs heightened secondary cortical processing.
By definition, the pain resembles cardiac pain in its sensation and distribution. It can be very intense and distressing, can disturb sleep, and may be worse during periods of emotional stress. Postprandial occurrence, in association with heartburn, suggests that it may be caused by reflux. When pain is associated with dysphagia, vigorous achalasia or oesophageal spasm are very possible.
Myocardial ischaemia should first be excluded as the cause. Endoscopy should then be performed followed by oesophageal pH and motility studies when symptoms are disabling. Investigation can be unrewarding.
Reassurance is essential to prevent repeated hospital admissions for fear of a cardiac cause. If the pain is triggered by gastro-oesophageal reflux, high-level acid-suppression therapy should be tried (see section on gastro-oesophageal reflux disease). Achalasia and diffuse oesophageal spasm should be treated on their own merits. In patients with no clear cut diagnosis, treatment with anxiolytics and antidepressants has been found to be moderately effective. Agents that reduce the strength of oesophageal contraction, such as calcium antagonists, appear ineffective in hypertensive peristalsis.
Oesophageal motor disorders secondary to systemic disease
Oesophageal motility may be affected by a number of systemic diseases (Table 4). These diseases may affect the striated or smooth muscle itself or the neural control.
The division of the oesophageal musculature into striated and smooth muscle components is revealed clearly by the myopathic diseases that affect the oesophageal musculature. In patients with peripheral myopathy this would normally have already been diagnosed. Weak or absent oesophageal contraction in the affected segment has the expected adverse impact on oesophageal transit, with a pattern of symptoms similar to the hypocontraction states of nonspecific oesophageal motor disorders (see above). The management of these dysfunctions is along general lines (see section on general management of oesophageal dysphagia).
|Table 4 Systemic diseases associated with disturbance to oesophageal symptoms|
|Systemic diagnosis||Oesophageal symptom(s)||Pathophysiology|
|Systemic sclerosis (limited and diffuse types)||Dysphagia, heartburn, regurgitation, weight loss||Oesophageal dysmotility, lower oesophageal sphincter incompetence, oesophagitis, columnar lined oesophagus|
|Mixed connective tissue disease||Dysphagia||Oropharyngeal and body dysmotility|
|Sjögren’s syndrome||Dysphagia||Xerostomia, oesophageal mucosal dryness|
|Polymyositis/dermatomyositis||Dysphagia, nasal regurgitation, aspiration||Oropharyngeal and body dysmotility|
|Systemic lupus erythematosus||Dysphagia, odynophagia|
|Rheumatoid arthritis||Dysphagia, odynophagia||Oesophageal body dysmotility, oesophageal vasculitis, atlantoaxial subluxation|
|Paget’s disease||Atlantoaxial subluxation, oesophageal vasculitis, secondary amyloid, micrognathia|
|Neuromuscular disorders||Dysphagia, chronic aspiration, disordered phonation|
|Myotonic dystrophy||Dysphagia||Oropharyngeal and oesophageal dysmotility|
|Myasthenia gravis||Dysphagia||Oropharyngeal and oesophageal dysmotility|
|Chronic intestinal pseudoobstruction||Dysphagia||Oesophageal dysmotility|
|Vasculitic syndromes||Dysphagia, odynophagia, chest pain, haematemesis||Oesophageal vasculitis, ulcers, pharyngeal stenosis|
|Diabetes mellitus||Dysphagia||Oesophageal dysmotility|
|Alcohol abuse||Dsyphagia, odynophagia, heartburn||Oesophageal dysmotility, oesophagitis, varices and haematemesis|
|Infiltrative disorders (amyloidosis, sarcoidosis)||Dysphagia||Oesophageal dysmotility|
Diseases of oesophageal smooth muscle
Systemic sclerosis (scleroderma)
60% of cases are limited cutaneous scleroderma, previously called CREST (calcinosis, Raynaud’s syndrome, (o)esophageal dysphagia, sclerodactyly, telangiectasia) syndrome. The remaining 40% of cases are now termed diffuse cutaneous scleroderma, with widespread involvement of other organs apart from the skin. The timing of onset of symptoms from oesophageal involvement are very variable in relation to other manifestations but are sometimes the presenting complaint. Oesophageal muscle atrophy and fibrosis are the cardinal features, but neuropathic abnormalities may also contribute to dysfunction. Smooth muscle peristalsis and the tone of the lower oesophageal sphincter is feeble or absent (Table 4).
Troublesome reflux symptoms are the most common consequence of loss of function. The pattern of dysphagia resembles that seen in nonspecific oesophageal motor disorder (see above). If dysphagia is severe, peptic stricture should be excluded, as complete loss of oesophageal smooth muscle peristalsis rarely leads to disabling dysphagia.
Reflux disease is frequently severe and should be managed by high-level medical therapy in order to prevent complications such as stricture (see above). Antireflux surgery is relatively contraindicated because of the poor propulsive function of the oesophageal body.
A scleroderma-like picture of oesophageal dysfunction is sometimes seen in other connective tissue disorders such as mixed connective tissue disease. The smooth muscle segment is also involved in systemic myopathies including polymyositis–dermatomyositis and myotonic dystrophy. It should be remembered that in addition to effects on motility rheumatological disorders may also lead to oesophageal symptoms via a combination of effects including mucosal dryness and associated reflux disease (Table 4).
Abnormal oesophageal motility is common in diabetes mellitus, and may be a feature of amyloidosis, chronic alcoholism, and the pseudoobstructive syndrome. In these disorders, the disturbance is believed to be primarily due to dysfunction of neural control mechanisms.
Disorders of striated muscle
Involvement of the striated muscle segment of the oesophagus is rare and patients usually present with high dysphagia, often in association with oropharyngeal dysfunction. The inflammatory myopathies (dermatomyositis, polymyositis, and inclusion body myositis), the muscular dystrophies (myotonia dystrophica and oculopharyngeal dystrophy), and myasthenia gravis are the most common causes.
General management of oesophageal dysphagia
Symptomatic treatment of dysphagia is frequently necessary because of the limited options and efficacy of specific treatments for oesophageal disorders. Although these measures may appear obvious, this aspect of management is commonly neglected by both patient and physician.
Optimization of bolus consistency
Large particles of solid food may impact on strictures. Large boluses require greater propulsive force even in the absence of stricture, and may trigger oesophageal spasm. Boluses should therefore be small and, in some circumstances, reduced to semiliquid or liquid form. Poor dentition should be treated. In some patients, defects of oesophageal function may be so severe that the diet should be puréed. Consultation with a dietitian will assist patients in identifying and preparing suitable food and in maintaining nutrition.
Assistance with oesophageal transit
Liquids assist transit by reducing the viscosity of food and providing a pressure head in the oesophagus. Gas generated within the oesophageal body from effervescent drinks can act as a piston which displaces oesophageal contents into the stomach in the erect position and may be sufficient to overcome an achalasic sphincter. The value of gravity in assisting transit should never be forgotten. Patients with severely impaired oesophageal transit should be advised to swallow medications in the upright position and with plenty of water so as to avoid injurious contact of the oesophagus with potentially corrosive tablets.
Alternative/supplementary approaches to feeding
Rarely, the above measures fail to maintain nutrition. Percutaneous endoscopic gastrostomy should then be used.
Oesophageal neoplasms (cancers)
The two most frequently occurring malignancies of the oesophagus are adenocarcinoma and squamous cell carcinoma, defined according to the histopathological characteristics. Occasionally mixed cell types are seen. Cure is only possible in the small minority (10–20%) of patients whose disease presents early. Several approaches are possible for palliation, although data are somewhat conflicting about the relative merits of each.
Oesophageal adenocarcinoma and tumours of the gastro-oesophageal junction
Over 80% of adenocarcinomas arising in the oesophagus occur in association with oesophageal columnar metaplasia, or Barrett’s oesophagus. In the cases with no co-incident Barrett’s the oesophageal mucous glands or the adjacent gastric cardia mucosa are presumably the source of malignant change.
As discussed above, columnar oesophageal metaplasia occurs in the context of chronic gastro-oesophageal reflux disease usually manifest as heartburn symptoms. The incidence of oesophageal adenocarcinoma has increased rapidly in Western countries over the past 20 to 30 years, surpassing the incidence of squamous cell carcinoma in these populations. The disease has a male preponderance. An increase in the prevalence of reflux disease related to the rise in obesity and reduced prevalence of Helicobacter pylori infection, with consequent increase in gastric acid secretion, are plausible explanations.
Dysplasia and carcinoma in situ are asymptomatic. Inexorable progression of dysphagia to solids, and eventually to liquids, over several weeks is the almost universal presentation. Dysphagia usually occurs only when the tumour has become circumferential or bulky. Sometimes, malignant mucosal ulceration presents with pain. Substantial weight loss has often occurred by the time of presentation.
Endoscopy and biopsy is the first investigation of choice. The lesion may be stricturing or exophytic. Multiple biopsies should be taken to avoid a missed diagnosis due to sampling bias. In stricturing lesions, dilatation for diagnostic purposes should be avoided if possible due to the risk of perforation. Biopsies can usually be taken from the proximal portion of the stricture even if intubation is limited. Brush cytology may be a useful adjunct to diagnosis but biopsies are preferable to confirm invasion. If performed, a barium swallow typically reveals a stricture with an irregular, lobulated mucosal outline. However, it is important to note that occasionally the barium appearance mimics a benign peptic stricture.
Occasionally, an asymptomatic oesophageal carcinoma is diagnosed when endoscopy is done for some other reason. Early lesions arising in Barrett’s mucosa may be inconspicuous endoscopically or be associated with a nodule or ulcer.
Staging using the TNM system is essential for all patients fit for radical therapy in order to optimize management. The staging criteria of gastro-oesophageal junction tumours will depend on whether the cancer is thought to arise primarily in the oesophagus or proximal stomach. CT scanning is very useful to determine nodal status and the presence of any distant metastases which most commonly affect the liver, lungs, adrenal glands and peritoneum. In order to obtain the best views the stomach should be distended with water before scanning. In the absence of metastatic disease on the CT scan, endoscopic ultrasound should be performed to determine the degree of invasion through the oesophageal wall (T stage). Paraoesophageal lymph nodes can also be assessed and sampled if necessary using fine needle aspiration. Positron emission tomography can provide further information on whether lymph nodes are involved and to characterize distant spread. Ideally this is now increasingly performed in combination with CT (CT-PET). Bronchoscopy or thoracoscopy can be useful to look for signs of airway infiltration in proximal disease.
For disease limited to the mucosa, endoscopic therapy may be sufficient. In early stage disease extending into the submucosa and beyond surgery is the treatment of choice as it achieves high rates of cure. The surgical approach depends on the location of the tumour. A transthoracic approach is standard (Ivor Lewis) but other options such as a transhiatal operation have a lower morbidity if a less radical lymph node resection is required. If lymph nodes are involved (N1) or if the cancer is invading through the muscularis and into the adventitia (T3) then multimodal therapy is usually required. By the time the disease is stage T2, it is usually associated with lymph node involvement. Multimodal therapy generally involves neo-adjuvant chemotherapy which in some cases is combined with radiotherapy prior to surgery. The precise algorithm will depend on the details of the individual case and the local expertise. Combined modality therapies have significant morbidity and mortality and an expert multidisciplinary approach, which takes into account quality of life issues for the patient, is required to achieve the best results.
When curative treatment is not possible, palliation of dysphagia poses many challenges and the field is hampered by a lack of critical comparisons. Surgery is not a good palliative option because of its morbidity and mortality. Radiotherapy applied as external beam or internal brachytherapy can provide useful relief from dysphagia. There may, however, be a temporary worsening of symptoms due to mucositis and nasogastric feeding may be required over this period. Peroral dilatation of malignant strictures, except prior to stent insertion, should be avoided due to the risk of perforation. Peroral placement of stenting tubes (usually covered, to prevent tumour ingrowth), laser photocoagulation, argon plasma coagulation, injection of sclerosants and radiotherapy (external beam or brachytherapy) are all options for the management of dysphagia which have potential for improving the quality of life. Laser and injection therapies are most useful when there is an exophytic tumour component. Stent insertion has the advantage of being a once-only treatment with immediate effect, although pain after insertion can sometimes be a problem. Alternative endoscopic therapies can provide more physiological improvements in swallowing.
Oesophagopulmonary fistula is a distressing development which usually causes pneumonia and persistent cough and which can sometimes be controlled by stenting. Bleeding can be managed with radiotherapy, argon plasma coagulation, or laser.
Palliative chemotherapy can increase survival and help symptoms in carefully selected patients fit enough to withstand the treatment. Other critical aspects of palliative care include pain control as well as nutritional advice and support (e.g. oral supplements) which are best done within the context of an expert multidisciplinary team.
This remains dismal except where screening programmes identify early, asymptomatic cases. In patients presenting with symptomatic disease only about one-quarter of patients are deemed to be potentially curable by surgery, and the overall 5-year survival rate is approximately 13%.
Squamous cell carcinoma
Squamous cell carcinoma has marked geographical variation. It is common in the developing world with an annual incidence of 6 in 100 000 men and 1.6 in 100 000 women. There are areas of especially high incidence (northern China, northern Iran, Kazakhstan, and the Transkei region of South Africa with >35/100 000 cases per year). Its incidence is stable in Western countries where it is six times more common in black men than in white men.
The striking geographical variation in incidence suggests a major aetiological contribution from environmental factors. The risk factors include heavy alcohol use, tobacco, and dietary factors including high rates of consumption of nitrosamines and aflatoxins. Other factors implicated are previous treatment for head and neck cancers, Plummer Vinson syndrome, human papilloma virus infection, vitamin A deficiency, chronic candida infection, injury to the oesophageal mucosa due to ingestion of a corrosive substance years previously, and chronic irritation from oesophageal retention in achalasia. Invasive carcinoma is preceded by mucosal dysplasia and carcinoma in situ and there may be a lag phase of many years which affords the possibility for screening in high-risk regions. Some patients may be genetically predisposed to this cancer. The best-documented example is tylosis, which is an autosomal dominant condition with associated palmar and plantar hyperkeratosis. Linkage studies suggest that the causative gene resides on chromosome 17q25.
Symptoms and staging
The presentation and investigation algorithms for squamous cell carcinoma are essentially as described for adenocarcinoma. Patients may present to the ear, nose and throat department if the dysphagia is very high or if hoarseness is a key symptom. Orolaryngsocopy may reveal the cause but flexible oesophagoscopy is usually required.
In very high-risk areas screening programmes have been set up which generally hinge on cytological sampling methods using either standard endoscopy or nonendoscopic balloons and mesh catheters. Lugol’s iodine spray can be very useful to highlight dysplastic mucosa and newer endoscopic techniques such as narrow band imaging can be a useful aid to diagnosis.
The treatment is essentially similar for all oesphageal malignancies. Squamous carcinomas are generally more radiosensitive than adenocarcinomas and radiotherapy can be given as definitive treatment either alone or combined with chemotherapy. The standard multimodal therapy generally involves neo-adjuvant chemotherapy, with or without radiotherapy, before surgery. Again the precise algorithm will depend on the details of the individual case and the local expertise. Unfortunately, for many patients palliative therapy is all that can be offered. Critical aspects of palliative care include pain control as well as nutritional advice and support (e.g. oral supplements) which are again best done within the context of an expert multidisciplinary team.
As for adenocarcinoma this remains dismal except where screening programmes identify early, asymptomatic cases. The overall 5-year survival rate is less than 20%.
Other primary oesophageal tumours
Other primary malignant tumours are rare and all have a poor prognosis. These include malignant melanoma, lymphoma, carcinoid, leiomyosarcoma, neuroendocrine carcinoma (small-cell carcinoma), adenoid cystic carcinoma, and pseudosarcoma reflecting the cell types present within the oesophagus. These tumours show a mixture of polypoid and infiltrating features and are usually only clearly distinguished from the more common malignancies by histology.
Although rare in the oesophagus, gastrointestinal stromal tumours (which were previously classified as smooth muscle tumours) are the most common benign oesophageal tumour although they may have malignant potential. Approximately one-half of patients are asymptomatic and the remainder exhibit symptoms which may include dysphagia, retrosternal chest pain, pyrosis, cough, odynophagia, and weight loss. Bleeding is unusual, in contrast to gastric gastrointestinal stromal tumours. They are usually intramural but can become pedunculated and they usually only cause symptoms if they are very large, or on a long pedicle. On endoscopy the mucosa is intact but there may be central umbilication or ulceration. Because of the submucosal nature of the lesion biopsy is often negative and endoscopic ultrasonography is a useful diagnostic tool which can be combined with fine needle aspiration. The majority have a gain of function mutation of the protooncogene growth factor receptor c-kit. The malignant potential is determined by the size and mitotic index. Most small lesions do not require treatment. Surgery should be considered in symptomatic patients or when the risk of malignant transformation is high. Treatment with a tyrosine kinase inhibitor can be useful for metastatic disease.
Other benign intramural tumours of the oesophagus include lipomas and granular cell tumours. The main risk of these is that they are mistaken for malignant tumours and operated on inappropriately.
Squamous cell papillomas of the mucosa can mimic a polypoid squamous carcinoma and so should be removed endoscopically for histological diagnosis.
Abnormalities of oesophageal anatomy
Non-neoplastic abnormalities which distort oesophageal anatomy may interfere with normal function or may merely pose difficulties in the interpretation of findings.
Sliding hiatus hernia
Around 90% of hiatus hernias are of this type, in which the gastro-oesophageal junction is displaced upwards into the thorax, giving a simple shaped pouch of intrathoracic stomach. This can be mistaken for a columnar-lined oesophagus unless the anatomical landmarks are clearly defined. These landmarks include the proximal extent of the gastric folds and the pallisading of vessels in the squamous oesophagus.
The phreno-oesophageal ligament is effaced in sliding hiatus hernia, but it is not clear whether this is a primary defect of gastric anchorage.
Many patients with hiatus hernia are asymptomatic. Despite this, physiological studies indicate that herniation of the gastro-oesophageal junction impairs its function as an antireflux barrier by removing the normal diaphragmatic crural compression from the lower oesophageal sphincter. Thus, hiatus hernia can be taken as a risk factor for reflux disease, but not an abnormality that makes the diagnosis.
Symptoms of gastro-oesophageal reflux are the only ones of major significance. These should be treated along conventional lines (see gastro-oesophageal reflux disease).
This is essentially that of any associated reflux disease.
Rolling or para-oesophageal hiatus hernia
A variable part of the stomach herniates through the hiatus alongside a normally situated gastro-oesophageal junction. This pattern of herniation may produce a gross disturbance of gastric anatomy, usually with a narrow exit from the herniated pouch into the main stomach cavity. Some rolling hernias are also associated with displacement of the gastro-oesophageal junction above the hiatus, in which case these are known as mixed hernias.
Obstruction and distension of the pouch causes upper abdominal discomfort and can progress to strangulation. Gastric volvulus can occur because of the laxity of the gastric anchorage and may obstruct the gastro-oesophageal junction. Both of these problems have a very high mortality and demand urgent surgery. It is controversial whether elective surgery should be performed to reduce and anchor rolling hiatus hernias in order to remove these risks.
Unfortunately, there are no adequate data on the degree of risk associated with rolling hiatus hernia.
Schatzki ring (B ring)
This is a characteristic short luminal stenosis which occurs at the gastro-oesophageal junction. It is made up only of mucosa and submucosa, and may narrow the lumen to a few millimetres or cause a clinically insignificant minor indentation.
This is unknown. They have been postulated to be congenital although evidence now suggests that they can occur in later life. Reflux and pill oesophagitis have been implicated.
With mechanically significant rings, intermittent dysphagia occurs on eating solids. Meat is often the culprit, leading to the common term of ‘steakhouse syndrome’. Episodes of bolus obstruction are not unusual, with associated chest pain caused by powerful oesophageal contractions. Failure to recognize a Schatzki ring frequently leads to the incorrect diagnosis of primary diffuse oesophageal spasm. Endoscopy is the investigation of choice. If barium studies are performed adequate distal oesophageal distension during the barium swallow is essential for detection and this is best achieved by prone-oblique views.
No treatment may be necessary. Disruption of the ring by simple peroral dilatation or endoscopic diathermy or laser is very rewarding, as the dysphagia and chest pain are cured, sometimes after many years of symptoms. However, there is a significant incidence of recurrence and repeated dilatations at intervals are often needed.
Other rings and webs
Other short oesophageal stenoses may develop because of peptic stricture, muscular rings, and cervical webs with iron-deficiency anaemia (Plummer–Vinson syndrome) or without.
Oesophageal diverticula and pseudodiverticula
Wide-mouthed multiple diverticula are characteristic of scleroderma oesophagus. In the nonsclerodermatous oesophagus diverticula occur in the mid and distal oesophagus, both types probably being ‘blow-outs’ secondary to hypercontraction motor disorders. These can become very large. It is rare for them to cause symptoms, but they may be associated with dysphagia and regurgitation of retained contents. Unless symptoms are disabling, they are best left undisturbed because leakage is common following surgical removal.
Multiple intramural outpouchings of barium are characteristic of intramural pseudodiverticulosis which appears to be due to dilatation of the ducts of submucosal glands by an unknown process.
Extrinsic oesophageal compression
This is a relatively common cause of dysphagia, and is most often a result of malignant mediastinal lymphadenopathy. Barium swallow or endoscopy usually shows a relatively long constriction of the oesophageal lumen of variable calibre, associated with a normal mucosal appearance. Dilatation of such a compression is usually unrewarding because of its elastic recoil. Mechanically significant extrinsic compression may also result from an enlarged heart, a dilated or unfolded aorta, or an aortic aneurysm. Kyphosis may accentuate the mechanical impact of these abnormalities. Mechanical changes along the cervical spine can also interfere with swallowing such as atlantoaxial spurs, osteophytes associated with osteoarthritis, and Forestier’s disease. In patients with rheumatoid arthritis atlantoaxial joint subluxation can lead to dysphagia and other signs of spinal cord compression (Table 4). Congenital vascular abnormalities can also compress the oesophagus in adults, an aberrant right subclavian artery being by far the most common.
Mechanical, chemical, and radiation trauma
These mucosal tears extend across the gastro-oesophageal junction and are normally induced by vigorous straining associated with vomiting. Bleeding is the only consequence of significance. In 10% of cases bleeding is severe enough to cause hypovolaemia. The history is usually quite characteristic, but definitive diagnosis requires endoscopy. Continued bleeding usually responds to endoscopic injection, electrocoagulation, vascular embolization, or vasopressin infusion. Very rarely, surgery is needed to under-run a persistently bleeding artery at the base of the tear.
Barogenic oesophageal rupture (Boerhaave’s syndrome)
In this uncommon condition, straining and vomiting cause oesophageal rupture, most often in the left lower third of the oesophagus. High-volume spillage of the gastric contents into the pleural space causes shock and pain in the chest and upper abdomen with radiation to the back, left chest, or shoulder. The chest radiograph becomes abnormal only some hours after rupture. Surgical repair and drainage are usually necessary, and if this is delayed beyond 24 h the mortality is very high. Unfortunately, diagnostic delay is not unusual.
Iatrogenic oesophageal perforation
Physicians encounter this problem most often as a result of their involvement in dilatation of oesophageal strictures, pneumatic bag dilatation for achalasia, or through problems with the management of oesophageal varices by balloon tamponade. Even with meticulous technique and appropriate equipment, oesophageal perforation can occur. Perforation is strongly suggested by development of chest or epigastric pain directly after instrumentation, sometimes with dyspnoea. Pneumothorax and surgical emphysema are diagnostic. Any suspicion of perforation should be acted upon by taking a chest radiograph which should be repeated in several hours if it is negative. Broad-spectrum antibiotics should be given on suspicion, as they are most effective in minimizing the risks of mediastinitis when given from the outset. Surgical consultation should occur promptly; the choice between conservative and surgical management needs to be individualized. Increasingly, instrumental perforation is being managed nonsurgically with nasogastric suction, antibiotics, and intravenous nutrition with good results, primarily because instrumental injury usually occurs when the stomach is empty.
Definition and aetiology
Strong acids and alkalis are both very damaging to the oesophagus and are found in high concentrations in many agents commonly used in the household for cleaning and maintenance. Laryngeal and gastric injuries may overshadow oesophageal injury. Because of their relative lack of taste, alkaline solutions are more likely to be swallowed accidentally in large amounts. Alkaline injury is especially deep; acid tends to form a superficial coagulant, which limits penetration.
The severity and extent of injury are immensely variable and cannot be predicted accurately from estimates of the volume ingested. Around one-half of patients with a history of caustic ingestion have no significant injury. Oropharyngeal and laryngeal injury confirm caustic ingestion and can be a major threat to the airway, but do not predict the existence and severity of oesophageal injury which causes odynophagia, dysphagia, or haematemesis. Prompt fibreoptic panendoscopy appears to be safe. This may be normal or show only patchy mucosal oedema, erythema, and small haemorrhagic ulcers, indicative of superficial damage with a good prognosis. Extensive and circumferential ulceration, and grey or brown/black ulceration suggest transmural injury.
Patients with severe injury must be observed closely for signs of perforation. Nasogastric suction should be used with the administration of broad-spectrum antibiotics as these appear to reduce the severity of infective complications. The use of steroids is controversial, the balance of evidence tending to oppose their use. Oesophageal stricture is to be expected with severe injury and appears not to be prevented by routine dilatation in the first 2 weeks after injury. A barium study should be done at 2 to 3 weeks to screen for stricturing, and then subsequently at about 3-monthly intervals thereafter for a year, so that the development of stricturing is recognized at a stage when dilatation may have some impact.
The main short- to medium-term risk is the development of stricture. Caustic strictures are difficult and hazardous to treat by peroral dilatation so that about half of patients require oesophageal resection. In the long term (average onset 40 years after injury) carcinoma of the oesophagus is a major hazard, the risk being 1000 to 3000 times the expected risk.
Chemotherapy-induced oesophageal problems
Chemotherapy causes oesophageal problems in several ways. Therapy may impair mucosal defences by affecting cell turnover leading to ‘mucositis’. This in turn may reduce resistance of the mucosa to damage from other agents, and increase susceptibility to infective oesophagitis from immune suppression. Oesophageal transit and acid clearance may be impaired through the neurotoxic effects of some agents. Fistulation or perforation may occur through cytotoxic effects on a malignancy in the oesophageal wall. It has been reported that combination chemotherapy is associated with the development of oesophageal columnar metaplasia in women being treated for breast cancer.
Other non-neoplastic mucosal diseases
Skin and systemic diseases associated with lesions of the oropharynx may also involve the oesophagus. These include epidermolysis bullosa, Behçet’s disease, lichen planus, pemphigus vulgaris, bullous pemphigoid, benign mucous membrane (cicatrial) pemphigoid, and drug-induced disease (Stevens–Johnson syndrome and toxic epidermal necrolysis).
Chronic, and less frequently acute, graft vs host disease may cause severe oesophageal problems through mucosal desquamation or mural damage. Resultant stricturing shows considerable variation in appearance. Rarely, Crohn’s disease can cause indolent, craggy ulceration and/or stricturing. Oesophageal sarcoidosis can mimic Crohn’s disease.