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Diseases of the oesophagus 

Diseases of the oesophagus
Chapter:
Diseases of the oesophagus
Author(s):

Rebecca Fitzgerald

DOI:
10.1093/med/9780199204854.003.1507_update_001

July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Chapter reviewed, minor changes made and further reading added.

Updated on 28 November 2012. The previous version of this content can be found here.
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Essentials

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, betel nuts, and other ingested sources and hence carcinomas can occur. Chronic reflux disease from exposure to corrosive upper gastrointestinal secretions are also associated with malignant disease—adenocarcinoma—as well as benign stricture formation related to the action of pepsin.

Introduction

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.

Investigation

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.

Endoscopy

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.

Radiology

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.

Gastro-oesophageal reflux disease

This is by far the most common oesophageal disorder and management should be tailored to the severity, which may vary considerably.

Definition

Some reflux of gastric and duodenal contents into the oesophagus occurs in everybody due to vagally mediated transient lower oeophageal sphincter relaxations. It should only be considered a disease when it gives rise to symptoms or complications sufficient to impair quality of life. Pathogenic reflux may occur without causing mucosal damage. The terms reflux or peptic oesophagitis should be reserved for circumstances when endoscopy demonstrates that the oesophageal mucosa is clearly breached by the action of the refluxed gastric contents. Minor changes such as erythema, oedema, or friability have been shown to be very unreliable indicators of the presence of oesophagitis. The disease can be further classified into oesophageal and extra-oesophageal syndromes using the Montreal classification.

Aetiology

In most patients reflux disease arises from the excessive exposure of the distal oesophagus to gastric contents which are primarily acid and/or bile. This is usually because of an abnormal frequency or duration of reflux episodes. In a few patients, however, symptoms arise with relatively normal levels of acid exposure, presumably because of sensitization of the oesophageal mucosa. In normal individuals excessive reflux is prevented by the lower oesophageal sphincter and an external sphincter formed by the crural diaphragm. Pathological reflux generally occurs as a result of defective neural control of the lower oesophageal sphincter. Hiatus hernia is common in patients with reflux disease and causes displacement of the sphincter from the hiatus formed by the diaphragmatic crura. Most reflux occurs during the day, usually after food, but lying down will ameliorate the antireflux effect of gravity and nocturnal reflux can be a disabling symptom. Refluxate is cleared from the oesophagus by peristalsis and swallowed saliva. Slow clearance of oesophageal acidification contributes significantly to prolonged acid exposure in about 50% of patients. This can be an important contributor to severe gastro-oesophageal reflux disease in systemic disorders such as scleroderma which affect gut motility.

Risk factors for gastro-oesophageal reflux disease include heritability (up to 30% of the risk), obesity, and age but not gender. Alcohol and smoking may play a role. Asthma increases the risk as do medications which relax the lower oesophageal sphincter such as calcium channel antagonists, nitrates, anticholinergics, and methyl xanthines.

Consequences of excessive reflux

Symptoms

These are an important source of disability. Evidence suggests that heartburn occurring on more than 2 days a week causes significant impairment of quality of life. However, presentation may be with the less specific symptom of dyspepsia (or epigastric discomfort), belching, nausea or with regurgitation, and dysphagia due to either stricture or motor dysfunction of the oesophageal body. There are a number of extra-oesophageal manifestations of reflux including respiratory symptoms such as hoarseness, persistent cough, and asthma. Chronic sinusitis, otalgia, and glue ear may also be associated with reflux.

Complications of reflux disease

The chemical insult from excessive exposure of the mucosa to gastro-duodenal contents leads to distal oesophageal erosion or ulceration in between 40 and 60% of patients with troublesome reflux symptoms and columnar-lined (Barrett’s) oesophagus in between 5 and 10% of individuals, as discussed in detail below. The extent of ulceration varies greatly, from tiny patches of erosion to extensive circumferential ulceration in a small minority. Peptic stricture sufficient to cause dysphagia is typically only associated with severe oesophagitis. When strictures are severe this may lead to malnutrition. Bleeding from oesophagitis may occur but is rarely life-threatening except when it occurs from a deep ulcer associated with columnar metaplasia.

Diagnosis and assessment of severity

History

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 for reflux disease. A trial of acid-suppression therapy can be used as an aid to diagnosis.

Endoscopy

When investigation is required, endoscopy is the first choice as it is the only test that can give sensitive recognition and grading of oesophagitis (e.g. Los Angeles classification system) and reliable diagnosis of oesophageal columnar metaplasia (Barrett’s oesophagus). Endoscopy also allows for the effective identification of significant peptic strictures, other types of oesophagitis (discussed below), and peptic ulcer disease as well as malignancies. The value of endoscopy as the initial investigation is greatly enhanced by the accurate diagnosis of endoscopic biopsy and, where indicated, cytology brushings. As discussed above, however, most patients with reflux disease do not have endoscopically visible mucosal damage, so a negative endoscopy does not exclude the diagnosis of reflux disease (so-called nonerosive reflux disease).

Oesophageal function tests

The place of these is summarized in Fig. 15.7.1. Oesophageal manometry and ambulatory 24-h pH monitoring have a limited but important role in the diagnosis of reflux disease (Fig. 15.7.2). Oesophageal pH monitoring is most useful in patients with troublesome symptoms but without endoscopic signs of oesophagitis in whom a trial of therapy has failed, and patients with atypical symptoms that cannot be clearly related to reflux. Patients with suspected reflux symptoms but with no endoscopic evidence of oesophagitis who are being considered for antireflux surgery should also undergo oesophageal pH monitoring.

Fig. 15.7.1 Principal decision paths for management of reflux disease.

Fig. 15.7.1
Principal decision paths for management of reflux disease.

Fig. 15.7.2 Section of a 24-h oesophageal pH monitoring study showing the association of heartburn with episodes of acid reflux after a meal.

Fig. 15.7.2
Section of a 24-h oesophageal pH monitoring study showing the association of heartburn with episodes of acid reflux after a meal.

Recently, multichannel oesophageal impedance monitoring (Fig. 15.7.3) has been shown to distinguish between swallowed or refluxed fluid and gas, although at present its use is mainly confined to the research setting. Combined with pH monitoring, it may identify individuals with ‘nonacid’ who fail to respond to treatment. Bile reflux can be assessed using Bilitec probes, but these are not routinely available anywhere.

Fig. 15.7.3 Example impedance images obtained from six impedance and two pH channels placed in the oesophagus. (a) Impedance changes for normal liquid swallow. Usually air is ahead of liquid bolus. (b) Mixed (gas and liquid) acid reflux episode. Mixed reflux is more frequent than liquid only reflux. Gas (belch) reflux is evidenced by short rise in impedance migrating rapidly into the proximal oesophagus. (c) Nonacid reflux. Oesophageal pH is unchanged, while impedance channels are showing a liquid reflux episode migrating into the proximal oesophagus.

Fig. 15.7.3
Example impedance images obtained from six impedance and two pH channels placed in the oesophagus. (a) Impedance changes for normal liquid swallow. Usually air is ahead of liquid bolus. (b) Mixed (gas and liquid) acid reflux episode. Mixed reflux is more frequent than liquid only reflux. Gas (belch) reflux is evidenced by short rise in impedance migrating rapidly into the proximal oesophagus. (c) Nonacid reflux. Oesophageal pH is unchanged, while impedance channels are showing a liquid reflux episode migrating into the proximal oesophagus.

(Courtesy of Qasim Aziz, Professor of Physiology, Barts and the London School of Medicine and Dentistry.)

Barium swallow and meal

This is an inappropriate primary diagnostic test; it is of no value for the detection of abnormal reflux, and is insensitive for the diagnosis of oesophagitis and cannot grade it. Other pathologies such as gastric ulcer and oesophageal stricture are demonstrated with reasonable sensitivity, but adequate evaluation of these findings requires endoscopic biopsy. However, barium swallow is the best method for recognizing extrinsic oesophageal compression which may be producing symptoms that could be interpreted as being due to reflux, and in the assessment of an anatomically complex hiatus hernia. The mere demonstration of hiatus hernia, however, does not necessarily indicate the presence of reflux disease.

Principles of management

The major aims of treatment are to provide adequate symptomatic relief and control of oesophagitis. Reduction of oesophagitis to minor patchy erosions is probably sufficient to prevent the complications of oesophagitis, although adequate symptomatic relief is usually achieved only when oesophagitis is completely healed.

Tailoring and titration of therapy

The severity and frequency of symptoms and the endoscopic findings should be used to choose an appropriate level of initial therapy (Fig. 15.7.1). There is some debate about whether to treat patients with a high or low dose of acid-suppressant drugs initially. An initial trial of low- to medium-dose empirical therapy has the disadvantage of giving less precise diagnostic information, and often gives only slow relief of symptoms. Patients with severe oesophagitis will usually not respond adequately to low dose acid-suppression. Initial high-dose proton pump inhibitor therapy is likely to give more immediate confirmation of the diagnosis and prompt relief of symptoms. For optimum cost-effectiveness and to reduce complications high dose treatment should be followed by a step-down approach to long-term therapy as outlined in Fig. 15.7.1.

Nondrug measures and antacids

The efficacy of these traditional approaches is often overrated. The most useful measures are avoidance of large meals and provocative foods, drinks, and physical activities. The benefits to reflux disease of stopping smoking, weight loss, and elevation of the bed head are uncertain. Antacids will not usually prevent symptoms, but may be effective in aborting episodes of heartburn. These low-cost measures are worth a trial in patients with mild intermittent symptoms and should be used as maintenance therapy if they prove effective, provided that their impact on lifestyle is acceptable to the patient.

Acid suppression

Inhibition of secretion of gastric acid makes gastric juice less injurious but does not stop reflux. This has deservedly become the most widely used drug therapy because of its high efficacy and adjustability. Proton pump inhibitors are the mainstay of treatment because of their effectiveness in reduction of food-stimulated acid secretion and their greater overall efficacy in control of acid secretion compared with histamine-2 receptor antagonists. However, histamine-2 receptor antagonists can be a useful adjunct to proton pump inhibitors for controlling nocturnal reflux.

Long-term treatment with acid suppressants maintains patients free of symptoms and oesophagitis indefinitely, but withdrawal is usually associated with prompt relapse. The maintenance dose appears to be the same as the lowest effective healing dose. There have been concerns about the safety of long-term acid suppression ever since the introduction of istamine-2 receptor antagonists. To date, follow-up of patients treated continuously for 10 years or more with acid suppression has shown no evidence of any effects of significance, but in the context of patients who may require treatment with these agents for decades, more extensive follow-up is still needed. Given these theoretical safety considerations and also drug cost, long-term treatment of reflux disease with these agents should use the lowest effective dose. In some patients use of proton pump inhibitors is limited by side effects such as diarrhoea and patients on long-term therapy may be prone to increased gastrointestinal infections due to loss of the antimicrobial effects of low gastric pH.

Motility stimulants

The best researched, most efficacious motility stimulant is cisapride, which is a parasympathomimetic that acts as a serotonin 5-HT4 receptor agonist. It mainly acts through enhancing oesophageal acid clearance as well as increasing muscle tone in the lower oesophageal sphincter. Unfortunately, cisapride can have effects on cardiac conductance that may rarely lead to sudden death at peak serum levels, especially when various drugs are co-administered. Cisparide has therefore been withdrawn from the market in many countries and should only be used cautiously in severe cases. Alternative prokinetics such as metoclopramide and domperidone may be useful adjuncts, again when used in combination with acid-suppression therapy.

Endoscopic antireflux procedures

Techniques include endoscopic suturing, radiofrequency energy delivery to the lower oesophageal sphincter, and submucosal prosthetic implants. Effectiveness has mainly been assessed in uncontrolled trials without long-term follow-up data. There is no place for such therapies outside clinical trials at present.

Antireflux surgery

In skilled hands, antireflux surgery is a very effective long-term therapy. Negative factors are the dependence of the results on the expertise of the surgeon and the morbidity and small (approximately 0.5%) mortality associated with the surgery itself. Laparoscopic antireflux surgery (usually a Nissen fundoplication) is a major advance, as it achieves good control of reflux with a major reduction in the morbidity inherent in the more traditional approach.

Choice between medical and surgical therapies

Selection of a medical or surgical therapy should take account of the severity of disease and the risks of antireflux surgery specific to the patient. It should also take account of the patient’s age, both from the point of view of operative risk and the time over which the patient will need treatment for reflux disease, the cost of effective medical therapy, and, naturally, the preferences of the patient. The choice between medical therapies should be largely governed by the local cost of the alternatives that give the necessary level of treatment, as all of the first-line options are effective, safe, and well tolerated.

Management of complications of reflux disease

The important complication of oesophageal columnar metaplasia is discussed in a separate section below.

Peptic stricture

Dysphagia secondary to stricture formation needs to be distinguished from the more common dysphagia seen in patients with reflux disease which is due to defective triggering and control of oesophageal body peristalsis (see the section on nonspecific oesophageal motor disorders, below). Peptic stricture is managed by a combination of peroral dilatation and healing of oesophagitis by either medical or surgical means. All strictures should be treated as malignant until proven otherwise by repeated biopsy. Provided oesophagitis is healed, stricture is usually not an ongoing problem.

Respiratory complications

Respiratory disease may occur either as a result of direct aspiration of refluxed gastric contents or from the reflex effects of gastro-oesophageal reflux. It is difficult to prove that reflux disease which coexists with respiratory disease is actually the cause of the respiratory problem. The best investigative approach is probably a trial of high-level acid inhibition with at least a double dose of proton pump inhibitor and prokinetics for at least 2 months. Management of respiratory disease by antireflux surgery is not guaranteed to be successful.

Regurgitation

Voluminous regurgitation is the main symptom in a small subgroup of patients with reflux disease. They may present complaining of vomiting, but a detailed history reveals that there is no prior nausea, and no effort involved in the appearance of the gastric content in the mouth. The determinants of high-volume reflux and regurgitation have not been defined. Treatment with proton pump inhibitors and prokinetics can have substantial benefits, but in more severe cases antireflux surgery is usually the only effective management.

Noncardiac chest pain

Reflux is also an important cause of noncardiac chest pain (see below).

Oesophageal columnar metaplasia (Barrett’s oesophagus)

Definition and nomenclature

Oesophageal columnar metaplasia (Barrett’s oesophagus) is defined as the conversion of the normal stratified squamous epithelium with a columnar-lined mucosa which may have characteristics of gastric or intestinal epithelium. The lack of international consensus on the definition of this disease has led to confusion in the literature. However, it is widely accepted that it is the subtype characterized by intestinal metaplasia with goblet cells which has the highest risk for malignant progression and in many countries the term Barrett’s oesophagus has been restricted to this subtype. The extent of the metaplasia may vary from 1 cm to the entire oeosophageal length and there appears to be a correlation between the length of the segment and the proximal extent of reflux exposure. The metaplasia generally starts in the distal oesophagus although discrete columnar islands may occur. The accepted nomenclature for describing the endoscopic features is the Prague classification in which C indicates circumferential involvement in centimetres and M is the maximal disease extent in centimetres (e.g. C2,M5 for a 5 cm segment with 3 cm of metaplastic tongues).

Aetiopathogenesis

Columnar metaplasia occurs in the context of chronic gastro-oesopageal reflux, predominantly in white males. Its incidence appears to have increased, even taking into account the more frequent use of endoscopy, and the reasons for this are still under intense scrutiny. Possible explanations include an increase in obesity leading to an increased susceptibility to reflux and the reduced prevalence of Helicobacter pylori infection with a consequent increase in gastric acid secretion. Columnar metaplasia carries a 40-fold increased risk for the development of oesophageal adenocarcinoma compared with the general population, which equates to an annual incidence of 0.1 to 0.4% in nondysplastic Barrett’s, depending on the length of the segment and the presence of intestinal metaplasia. The risk for cancer significantly increases with the presence of dysplasia and endoscopic surveillance is therefore generally advocated.

Management

Surveillance hinges on the subjective interpretation of dysplasia in multiple, random biopsies (usually quadrantic biopsies every 2 cm according to the Seattle protocol). The frequency of surveillance depends on the degree of dysplasia (Table 15.7.1). This arduous protocol has not been uniformly accepted since no data from randomized controlled trials support a reduction in population mortality from oesophageal adenocarcinoma using this approach. On the other hand, the outcome for individuals with symptomatic invasive adenocarcinoma is universally poor compared with surveillance-detected disease. Failure to discuss the risk for adenocarcinoma and the option of endoscopic surveillance with a patient who has oesophageal columnar metaplasia could well be viewed as an indefensible lapse of practice, despite the uncertainties about cost-effectiveness.

Table 15.7.1 Surveillance protocol for columnar lined (Barrett’s) oesophagus for patients willing and fit to undergo regular endoscopy

Histopathological diagnosis

Endoscopy frequency

Clinical management

  • Intestinal metaplasia

  • No dysplasia

2 years

Treat heartburn symptoms with PPI

  • Intestinal metaplasia

  • Indefinite intraepithelial neoplasia/dysplasia

6 months after index finding. Annual if changes persist. Revert 2 yearly when 2 consecutive endoscopies no dysplasia

Ensure adequate acid suppression to prevent inflammation confounding diagnosis

  • Intestinal metaplasia

  • Low grade intraepithelial neoplasia

6 months after index finding. Annual if changes persist. Revert 2 yearly when 2 consecutive endoscopies no dysplasia (caution if multifocal change)

Ensure adequate acid suppression to prevent inflammation confounding diagnosis

  • Intestinal metaplasia

  • High grade intraepithelial neoplasia

Confirm diagnosis with assessment by two independent pathologists

  • Consider endoscopic therapy—method depending on comorbidity and focality of lesion

  • If endoscopic resection shows disease extending into the submucosa, surgical resection is recommended

The treatment of high-grade intraepithelial neoplasia (dysplasia) in oesophageal columnar metaplasia is controversial. First, the diagnosis should be corroborated by two independent pathologists (Table 15.7.1). Increasingly, endoscopic mucosal resection can be used as a diagnostic adjunct to determine depth of invasion. This will inform management decisions and in some cases will turn out to be a therapeutic local excision. Endoscopic ultrasound may be useful but there is a danger of overestimating the depth of invasion. The management options will be determined by the extent of dysplasia and the fitness of the individual as well as local expertise. Oesophagectomy (which may be performed as a transhiatal or a laparoscopic procedure with a limited lymph node resection) is now generally reserved for invasive disease extending into the submucosa since endoscopic resection of localized lesions coupled with ablative therapy, generally using radiofrequency ablation, is now supported by randomized control trial evidence with encouraging data on durability. Some centres favour frequent continued surveillance until there is clear evidence of invasion but with the advent of effective endoscopic therapies this is questionable. Lack of detailed knowledge about the natural history of high-grade dysplasia makes the decision-making process especially difficult. Discussion with a multidisciplinary team with expertise in oesophageal cancer is recommended, as well as full consultation with the patient.

Barrett’s oesophagus may also be associated with deep benign oesophageal ulceration within the columnar-lined segment and strictures usually at the squamocolumnar junction. Very rarely ulcers can erode into mediastinal structures or the pleural space although this is encountered much less frequently with the ready availability of acid suppressants.

The diagnosis and management of invasive oeosphageal adenocarcinoma are discussed in the malignancy section.

Nonreflux causes of oesophagitis

Infective oesophagitis

Infective oesophagitis has become more prevalent with the increasing number of people who are immunosuppressed through HIV infection or chemotherapy. The more important causes of infective oesophagitis are summarized in Table 15.7.2. Immune status is a major determinant of the pattern of infection and simultaneous infection with two or more infective agents is not unusual (Table 15.7.2). Helicobacter pylori does not appear to be of any primary significance in the pathogenesis of oesophageal mucosal disease.

Table 15.7.2 Major causes of infective oesophagitis

Pathogen

Management

Remarks

Immunocompetent patients

Candida albicans

Topical/oral antifungals

By far the most common

Herpes simplex

Aciclovir if severe

Unusual, may denude mucosa

Varicella zoster

Aciclovir if severe

In association with chickenpox/herpes zoster

Bacteria

Rare in well individuals

Immunocompromised patients

Candida albicans

Systemic antifungals

Most common; oral disease almost diagnostic

Cytomegalovirus

Prophylaxis and treatment with ganciclovir or foscarnet

Serpiginous to giant ulcers in distal half

Herpes simplex

Prophylaxis and treatment with aciclovir or foscarnet

Circumscribed ulcers, raised edges to coalescence. Oral lesions

Tuberculosis

Conventional

From miliary and local spread

Gram-positive cocci, Gram-negative bacilli

Intravenous antibiotics

Often with systemic infection

Syphilis

Conventional

Associated with tertiary syphilis elsewhere. Inflammatory stricture

Patients may present with pain or dysphagia. Viral oesophagitis can sometimes cause major haemorrhage. The dysphagia is generally secondary to superficial mucosal damage and inflammation, but some disorders damage the full thickness of the oesophageal wall and so lead to stricturing.

A full history to determine the setting in which the oesophageal problem occurs is often very helpful. Cutaneous or oral disease can inform the oesophageal diagnosis. Endoscopy is the investigation of choice since the mucosal appearance and the distribution of oesophageal lesions can be virtually diagnostic. In addition, biopsies and brushings allow for histological diagnosis and identification of fungal elements, viral inclusions, or rarely, pathogenic bacteria.

Although infective oesophagitis may be severe in immunocompetent patients it is characteristically self-limiting and topical therapy is normally all that is needed. Immunocompromised patients usually need aggressive, systemic therapy to resolve the infection (Table 15.7.2). Some infections tend to recur, which can cause major disability.

Eosiniphilic oesophagitis

Eosinophilic oeosphagitis (sometimes referred to as allergic oesophagitis) affects children and adults worldwide, with a male preponderance. The incidence appears to be increasing in line with other associated allergic conditions such as asthma, hay fever, allergic rhinitis, and atopic dermatitis. Although the exact aetiology is not understood there does seem to be an aberrant immune-mediated response and activated eosinophils may cause activation of acetyl choline via histamine. Food impaction and dysphagia are the common presenting symptoms. Heartburn is often present but refractory to standard treatments for gastro-oesophageal reflux disease. Approximately 50% of patients will have other allergic symptoms. Endoscopy is the investigation of choice and the findings range from grossly abnormal to normal. Findings include a small-calibre oesophagus, proximal strictures, white exudates, oeosphageal rings, and fragile mucosa. The diagnosis is made on oesophageal biopsy in which there is a dense eosiniphilic infiltration within the epithelium (>15 per high power microscopy field) in both proximal and distal biopsies; and exclusion of other possible causes including proton pump responsive oesophageal eosinophilia (Fig. 15.7.4). If the eosinophilic infiltration is more generalized this suggests eosinophilic gastroenteritis. There is a lack of randomized controlled trial evidence to guide treatment. Strategies include dietary elimination in consultation with an allergy assessment and steroids given topically or systemically in severe cases. Endoscopic food disimpaction and dilatation may be necessary. There are some data on leukotriene inhibitors and anti-interleukin-5 antibody therapy, but limited data on the long-term outcome for these patients.

Fig. 15.7.4 Histopathological appearance of eosinophilic oesophagitis: Low power (a) and high power (b).

Fig. 15.7.4
Histopathological appearance of eosinophilic oesophagitis: Low power (a) and high power (b).

(Courtesy of Vicki Save, Lothian University Hospital, NHS Trust.)

Medication-induced oesophagitis

This entity was only recognized in 1970. The chemical properties of medications pose hazards to the oesophageal mucosa because of its relative susceptibility to injury through pH-dependent mechanisms. This susceptibility arises in part from the high local concentrations of medications that occur in the oesophageal lumen, since pills move surprisingly slowly through the normal oesophagus especially at the level of the aortic arch. Defective oesophageal transport, poor pill design, increased mucosal susceptibility to injury, and poor pill-taking technique contribute to the problem. Medications known to have an especially high risk for oesophageal damage are listed in Table 15.7.3.

Table 15.7.3 Common causes of medication-induced oesophagitis

Severe injury—high risk

Slow-release potassium chloride

Aspirin and nonsteroidal anti-inflammatory drugs

Doxycycline/tetracycline

Quinidine

Alendronate

Potassium chloride

Less severe injury—high risk

Many antibiotics

Iron supplements

Occasional injury

Ascorbic acid

Mexiletine

Slow-release theophylline

Captopril

Phenytoin

Zidovudin

Corticosteroids

Symptoms are those for any form of stricture associated oesophagitis, and much pill-induced injury probably goes unrecognized. Injury at the distal oesophagus, the other common site of hold-up, may be commonly misdiagnosed as being due to reflux disease.

Medications and formulations with a high risk of injury should be identified and avoided if possible, especially in older patients with reflux disease or abnormal oesophageal transit. Pill transit is facilitated if medications are taken in the erect position with plenty of water. Pharmaceutical companies need to pay more attention to the use of shapes, sizes, and coatings that can assist transit of pills through the oesophagus. Stricturing may occasionally require surgery.

Caustic injury

See ‘Caustic ingestion’, below.

Primary oesophageal motor disorders

Idiopathic achalasia and achalasia-like states

Definition

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.

Aetiology

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.

Symptoms

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.

Diagnosis

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 (Fig. 15.7.5).

Fig. 15.7.5 Chest radiograph and barium studies from a case of advanced achalasia.

Fig. 15.7.5
Chest radiograph and barium studies from a case of advanced achalasia.

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.

Treatment

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. Randomized controlled trial evidence shows that laparoscopic myotomy has similar efficacy to pneumatic dilation, and both procedures have a risk of leading to troublesome gastro-oesophageal reflux (10–20%). In patients having surgery 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.

Prognosis

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.

Diffuse oesophageal spasm

Definition

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.

Aetiology

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.

Symptoms

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.

Diagnosis

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.

Treatment

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.

Prognosis

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

Definition

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 (Fig. 15.7.6). 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.

Fig. 15.7.6 Oesophageal manometric tracing in a patient with hypertensive peristalsis.

Fig. 15.7.6
Oesophageal manometric tracing in a patient with hypertensive peristalsis.

Aetiology

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.

Symptoms

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

Definition

These are departures from normal patterns of oesophageal motor function which do not actually define specific diseases, but which are of clinical significance. These are separate from oeosphageal dysmotility arising in association with diseases such as gastro-oesophageal reflux disease, diabetes, and other autonomic neuropathies. Nonspecific oesophageal motor disorder is the commonest single functional diagnosis made in most oesophageal manometric laboratories.

Aetiology

There are likely to be several mechanisms involved. The intermittent occurrence of dysfunctions suggests that they are due to defective neural control.

Symptoms

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.

Treatment

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.

Prognosis

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

Definition

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.

Aetiology

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.

Symptoms

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.

Diagnosis

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.

Treatment

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 15.7.4). These diseases may affect the striated or smooth muscle itself or the neural control.

Table 15.7.4 Systemic diseases associated with disturbance to oesophageal symptoms

Systemic diagnosis

Oesophageal symptom(s)

Pathophysiology

Rheumatological disorders

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

Seronegative spondyloarthropathies

Dysphagia

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

Other disorders

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

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).

Diseases of oesophageal smooth muscle

Systemic sclerosis (scleroderma)

Definition and aetiology

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 15.7.4).

Symptoms

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.

Treatment

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.

Other rheumatological disorders

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 15.7.4).

Other disorders

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 (see Chapter 15.6). 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

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

Definition

Over 80% of adenocarcinomas arising in the oesophagus occur in association with oesophageal columnar metaplasia, or Barrett’s oesophagus (Fig. 15.7.7). 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.

Fig. 15.7.7 Barrett’s associated adenocarcinoma. (a) demonstrates the endoscopic view in which tongues of salmon pink columnar lined mucosa are seen extending beyond the exophytic tumour mass. (b) is the corresponding endoscopic ultrasound image of this case in which the tumour is seen to invade through the muscularis (T3).

Fig. 15.7.7
Barrett’s associated adenocarcinoma. (a) demonstrates the endoscopic view in which tongues of salmon pink columnar lined mucosa are seen extending beyond the exophytic tumour mass. (b) is the corresponding endoscopic ultrasound image of this case in which the tumour is seen to invade through the muscularis (T3).

Aetiology

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.

Symptoms

Dysplasia and carcinoma in situ are asymptomatic and this has led to discussions about screening in high-incidence areas of the world. 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

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 (Fig. 15.7.8). 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) (see Fig. 15.7.7). 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.

Fig. 15.7.8 (a) Transaxial CT staging of a type 3 tumour of the gastro-oesophageal junction (primarily within the proximal stomach and extending into the oesophagus). (b) Reformatted view of a gastro-oesophageal junction tumour with extensive involvement of lower oesophagus extending into the proximal stomach with proximal oesophageal dilatation.

Fig. 15.7.8
(a) Transaxial CT staging of a type 3 tumour of the gastro-oesophageal junction (primarily within the proximal stomach and extending into the oesophagus). (b) Reformatted view of a gastro-oesophageal junction tumour with extensive involvement of lower oesophagus extending into the proximal stomach with proximal oesophageal dilatation.

(Courtesy of Dr Nicholas Carroll, Consultant Radiologist, Addenbrooke’s Hospital Cambridge.)

Treatment

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.

Prognosis

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.

Aetiology

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 (Fig. 15.7.9).

Fig. 15.7.9 Lugol’s iodine spray reveals early squamous cell carcinoma as seen by white light (a) and with narrow-band imaging (b).

Fig. 15.7.9
Lugol’s iodine spray reveals early squamous cell carcinoma as seen by white light (a) and with narrow-band imaging (b).

(Courtesy of Mr Peter Safranek, Consultant Upper Gastrointestinal Surgeon, Addenbrooke’s Hospital, Cambridge.)

Treatment

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.

Prognosis

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

Definition

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.

Aetiology

The phreno-oesophageal ligament is effaced in sliding hiatus hernia, but it is not clear whether this is a primary defect of gastric anchorage.

Symptoms

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.

Treatment

Symptoms of gastro-oesophageal reflux are the only ones of major significance. These should be treated along conventional lines (see gastro-oesophageal reflux disease).

Prognosis

This is essentially that of any associated reflux disease.

Rolling or para-oesophageal hiatus hernia

Definition

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.

Symptoms

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.

Prognosis

Unfortunately, there are no adequate data on the degree of risk associated with rolling hiatus hernia.

Schatzki ring (B ring)

Definition

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.

Aetiology

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.

Symptoms

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 (Fig. 15.7.10). 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.

Fig. 15.7.10 Endoscopic appearance of a Schatzki ring.

Fig. 15.7.10
Endoscopic appearance of a Schatzki ring.

(Courtesy of Dr Ewen Cameron, Consultant Gastroenterologist, Addenbrooke’s Hospital, Cambridge.)

Treatment

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 15.7.4). 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

Mallory–Weiss tear

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.

Caustic ingestion

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.

Symptoms

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.

Treatment

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.

Prognosis

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.

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