**2. Evaluation**

The most common causes of esophageal dysphagia are listed in Table 1.


**Table 1.** Common diseases of esophageal dysphagia and endoscopic management

The acceptance of endoscopy as a gold standard for testing for mucosal disease may bias evaluations of the sensitivity of other diagnostic modalities. Given that endoscopy was used as the gold standard for mucosal disease, the sensitivity of radiology could not have exceeded that of endoscopy [3].

If the patient history, barium swallow, or both suggest achalasia, manometry to confirm the diagnosis should generally precede the endoscopic evaluation, to better prepare for endo‐ scopic therapy.

### **2.1. GERD: Peptic esophageal stricture**

**2. Evaluation**

92 Seminars in Dysphagia

**Benign diseases** Yes

Esophageal web Yes

Eosinophilic esophagitis Yes

Caustic injury Yes

Radiation injury Yes

Drug-induced stricture Yes

Postendoscopic therapy stricture Yes

Diffuse esophageal spasm No

**Table 1.** Common diseases of esophageal dysphagia and endoscopic management

**Malignant diseases**

squamous cell)

**Motility disorders**

Esophageal carcinoma (adeno and

The most common causes of esophageal dysphagia are listed in Table 1.

Bougie Balloon

Peptic stricture Yes Transoral incisionless fundoplication

Schatzki ring Yes Electrocautery incision with a needle-knife

Anastomotic stricture Yes Biodegradable stent

Head and neck tumor No Self-expanding metal stents (SEMS)

Extrinsic compression No Self-expanding metal stents (SEMS)

Achalasia Yes Peroral endoscopic myotomy (POEM)

**Endoscopic dilation Other endoscopic treatments**

Radiofrequency ablation

Injection of corticosteroids or triamcinolone

papillotome

Yes Self-expanding metal stents (SEMS)

Injection of botulinum toxin

White light endoscopy is now the standard investigation procedure for identifying esophageal injury. An experienced endoscopist who takes the time to methodically inspect the esophagus is generally expected to succeed in diagnosing reflux esophagitis. There has been evidence, however, of interindividual variability in the endoscopic diagnosis of erosive reflux esopha‐ gitis and other lesions of the upper gastrointestinal tract. Krugmann reported detailed endoscopic findings for GERD [4]. Peptic esophageal stricture as a consequence of gastroeso‐ phageal reflux disease is the most frequent among benign esophageal strictures [6]. The typical case of peptic esophageal stricture is shown in Figure 1. There are multiple etiologies for benign esophageal stricture or stenosis, but the most frequent is the peptic stricture resulting from pathologic acid exposure in GERD. Dysphagia is a common symptom. When dysphagia is encountered, accurate diagnostic procedures (barium esophagogram, upper endoscopy with biopsies) have to be performed to exclude malignant causes first. Strictures can be divided into two categories anatomically: "simplex" or "complex." The former are short, focal, nonangu‐ lated, and wide enough to allow an endoscope to easily pass through. The latter are long and angulated, with a severely narrowed diameter. The strictures are also sometimes scored based on three parameters to optimize the therapeutic decisions: the stricture diameter, stricture length, and degree of difficulty of stricture dilation [7]. After this scoring, the stricture can be classified as type I (mild), type II (moderate), or type III (severe or critical). This classification is also useful for predicting the most appropriate therapeutic option.

**Figure 1.** Peptic structure

### **2.2. NERD (Nonerosive Reflux Disease)**

NERD is a subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions or breaks on conventional endoscopy, without recent acid-suppressive therapy [8]. Most patients with typical reflux symptoms show no evidence of erosive esophagitis on endoscopy. Upper gastrointestinal endoscopy is required to establish a diagnosis of NERD. Further investigation is required when alarming symptoms are present. Routine random biopsy is not currently recommended for the diagnosis of NERD. Additional diagnostic information is provided by ambulatory 24-hour intraesophageal pH-metry and impedance measurement with reflux-related symptom correlation.

#### **2.3. Schatzki ring and esophageal web**

Narrowing of the esophagus can be due to either a benign or malignant stricture formation, webs (mucosa or submucosa alone), or rings (mucosa, submucosa, and muscle). Esophageal rings and webs are both membranous structures in which a thin fold of tissue creates at least a partial obstruction of the esophageal lumen. Esophageal webs usually measure 2–3 mm wide. The obstruction is a smooth extension of normal esophageal tissue made up of mucosa or submucosa alone. Webs can be found anywhere along the esophagus, but classically they appear in the anterior postcricoid area of the upper esophagus. A web at this site constitutes the Paterson Brown–Kelly syndrome, otherwise known as Plummer–Vinson syndrome in the USA [9].

Esophageal rings are concentric, smooth, thin extensions of normal esophageal tissue, usually 3–5 mm thick. They consist of mucosa, submucosa, and muscle. Rings are often detected incidentally at barium studies or endoscopy. There is no sex difference in the incidence of rings overall, though multiple rings are usually found in young men. Rings are classified as types A, B, and C [9]. The A ring, an uncommon type located a few centimeters proximal to the esophagogastric squamocolumnar junction, is thought to be caused by normal physiologic smooth muscle contractions. The B ring (more commonly known as Schatzki ring) is actually a web, as it involves only mucosa and submucosa and tends to appear in the distal esophagus and as the proximal part of a hiatus hernia. The B ring is nonprogressive and usually presents in patients aged over 50 who experience intermittent dysphagia to solid food over periods spanning months or years. The C ring, another rare type, is found in the most distal portion of the esophagus. On X-ray, the C ring manifests as an indentation caused by diaphragmatic crural pressure. A and C rings are both unlikely to be readily seen on upper endoscopy. Hence, the B ring (Schatzki ring) is the most common esophageal ring found on either esophagogram or endoscopy. Schatzki rings rarely cause symptoms. Overall, esophageal rings with luminal narrowing significant enough to cause symptoms (13 mm or less) are seen in only about 0.5% of all esophagograms.

#### **2.4. Head and neck tumor and esophageal tumor**

A core cancer-specific symptom of head and neck tumors is difficulty in swallowing [10]. Most patients with tumors of the head and neck or esophagus present for medical attention because of dysphagia.

Among the many symptoms of esophageal cancer, dysphagia may have an especially adverse effect on quality of life (QOL) [11]. Dysphagia is the predominant symptom in more than 70% of patients with esophageal cancer. The optimum management of dysphagia caused by advanced primary EC has not yet been established, although continued progress toward this goal has been achieved in recent years.

Apart from the weight loss that may result, an inability to swallow comfortably or a tendency to regurgitate food may spoil meals shared with families and friends or induce patients to withdraw from social situations.

Granular cell tumors and solitary fibrous tumors of the cervical esophagus also cause dys‐ phagia [12, 13].

### **2.5. Eosinophilic esophagitis and infection**

**2.2. NERD (Nonerosive Reflux Disease)**

94 Seminars in Dysphagia

**2.3. Schatzki ring and esophageal web**

USA [9].

of all esophagograms.

of dysphagia.

**2.4. Head and neck tumor and esophageal tumor**

NERD is a subcategory of GERD characterized by troublesome reflux-related symptoms in the absence of esophageal mucosal erosions or breaks on conventional endoscopy, without recent acid-suppressive therapy [8]. Most patients with typical reflux symptoms show no evidence of erosive esophagitis on endoscopy. Upper gastrointestinal endoscopy is required to establish a diagnosis of NERD. Further investigation is required when alarming symptoms are present. Routine random biopsy is not currently recommended for the diagnosis of NERD. Additional diagnostic information is provided by ambulatory 24-hour intraesophageal pH-metry and

Narrowing of the esophagus can be due to either a benign or malignant stricture formation, webs (mucosa or submucosa alone), or rings (mucosa, submucosa, and muscle). Esophageal rings and webs are both membranous structures in which a thin fold of tissue creates at least a partial obstruction of the esophageal lumen. Esophageal webs usually measure 2–3 mm wide. The obstruction is a smooth extension of normal esophageal tissue made up of mucosa or submucosa alone. Webs can be found anywhere along the esophagus, but classically they appear in the anterior postcricoid area of the upper esophagus. A web at this site constitutes the Paterson Brown–Kelly syndrome, otherwise known as Plummer–Vinson syndrome in the

Esophageal rings are concentric, smooth, thin extensions of normal esophageal tissue, usually 3–5 mm thick. They consist of mucosa, submucosa, and muscle. Rings are often detected incidentally at barium studies or endoscopy. There is no sex difference in the incidence of rings overall, though multiple rings are usually found in young men. Rings are classified as types A, B, and C [9]. The A ring, an uncommon type located a few centimeters proximal to the esophagogastric squamocolumnar junction, is thought to be caused by normal physiologic smooth muscle contractions. The B ring (more commonly known as Schatzki ring) is actually a web, as it involves only mucosa and submucosa and tends to appear in the distal esophagus and as the proximal part of a hiatus hernia. The B ring is nonprogressive and usually presents in patients aged over 50 who experience intermittent dysphagia to solid food over periods spanning months or years. The C ring, another rare type, is found in the most distal portion of the esophagus. On X-ray, the C ring manifests as an indentation caused by diaphragmatic crural pressure. A and C rings are both unlikely to be readily seen on upper endoscopy. Hence, the B ring (Schatzki ring) is the most common esophageal ring found on either esophagogram or endoscopy. Schatzki rings rarely cause symptoms. Overall, esophageal rings with luminal narrowing significant enough to cause symptoms (13 mm or less) are seen in only about 0.5%

A core cancer-specific symptom of head and neck tumors is difficulty in swallowing [10]. Most patients with tumors of the head and neck or esophagus present for medical attention because

impedance measurement with reflux-related symptom correlation.

The incidence of eosinophilic esophagitis (EoE) is registering an increase in adults. An allergic reaction to food is now established to play an important role in its etiology, and dietary interventions and biologic agents to block the inflammatory cascade are thought to hold promise as novel fields of clinical research. Biopsies should be obtained from the proximal and distal esophagus to evaluate for eosinophilic esophagitis in patients who present with dysphagia together with endoscopic findings suggestive or not suggestive of EoE, and also in patients without esophageal mechanical obstruction. Patients usually present with dysphagia, food impaction, and/or reflux-like symptoms, and biopsy of the esophagus typically shows more than 15 eosinophils per high-power field [14]. The dysphagia predominantly seen in EoE has been attributed to both organic and nonorganic (i.e., motility) disorders. Endoscopically, a normal-appearing esophagus is usually incompatible with a diagnosis of EE, although the findings can be subtle. EGD findings implicative of EoE include an attenuation of the subepi‐ thelial vascular pattern, linear furrowing (possibly extending along the whole length of the esophagus), surface exudates composed of eosinophils, or abscesses or strictures [15,16].

Endoscopic evaluation of the gastrointestinal tract remains a cornerstone of diagnosis, especially in patients with advanced immunodeficiency who are at risk for opportunistic infections (OIs) [17]. Infectious esophagitis may be caused by fungal, viral, bacterial, or even parasitic agents [18]. Acute onset of symptoms such as dysphagia and odynophagia is typical of this condition. Candida esophagitis most commonly appears in patients with hematologic malignancies or AIDS, or who use steroids for the treatment of disorders. Candida esophagitis is usually diagnosed when white mucosal plaque-like lesions are seen on esophagogastro‐ duodenoscopy. HSV esophagitis occurs most frequently in solid organ and bone marrow transplant recipients.

The diagnosis of herpes simplex virus esophagitis is usually based on endoscopic findings confirmed by histopathological examination. Well-circumscribed ulcerous lesions with a "volcano-like" appearance may appear in the mucosa of the distal esophagus, typically with diameters of less than 2 cm. Diffuse erosive esophagitis may also be present.

Cytomegalovirus esophagitis is observed in patients who have undergone transplanta‐ tion, are on long-term dialysis, are infected with HIV, or are receiving chronic steroid therapy. Esophagogastroduodenoscopy usually reveals large solitary ulcers or erosions in the distal esophagus.

#### **2.6. Esophagitis induced by caustic injury, radiation injury, or drugs**

A patient with a usual history of caustic substance ingestion and prolonged hospitalization for severe caustic damage was hospitalized again because of an increase in dysphagia and odynophagia [19]. The gold standard of safely assessing the depth, extent of caustic ingestion injury, and appropriate therapeutic regimen is EGD. The patients underwent EGD within 24 hours of admission and mucosal damage was graded using Zagar's modified endoscopic classification scheme [19].

Radiation therapy (RT), the primary modality for patients with tumors of the upper aerodigestive tract, allows larynx preservation [20]. Proximal esophageal strictures occur in 2–16% of patients after radiation therapy for cancers of the lung or head and neck. RT-induced laryngeal edema (due to inflammation and lymphatic disruption) is a common and expected side effect. Progressive edema and associated fibrosis detected by endoscope or barium swallowing can lead to long-term problems with phonation and swallowing. Aspiration pneumonia associated with dysphagia after intensive chemo radiation therapy has recently been reported at a growing frequency.

Drug-induced esophagitis mainly presents as chest pain, odynophagia, and dysphagia. In the agents known to induce esophagitis, antibiotics are the most common culprit. Other causative agents include nonsteroidal anti-inflammatory drugs, antihypertensive drugs, acetamino‐ phen, oral hypoglycemic agents (glimepiride), bisphosphonates (alendronate, ibandronate), ascorbic acid, and warfarin [21]. The most frequent endoscopic site of drug-induced esopha‐ gitis is the middle third of the esophagus. On endoscopy, drug-induced esophagitis manifests as ulcers of various forms such as kissing ulcers, erosions, or ulcers with bleeding, as patchy sections coated with drug materials or impacted pill fragments, or sometimes as strictures.

#### **2.7. Achalasia**

Achalasia is regarded as a disease exclusively involving the smooth muscle. About 70–80% of patients have absent or incomplete lower esophageal sphincter (LES) relaxation with wet swallows, while the remainder have complete but shortened relaxation [22]. The typical endoscopic findings are shown in Figure 2A,B. Patients with esophageal stasis are often unaware of this condition. Heartburn, though not infrequent, bears little relationship to the esophageal acid exposure in achalasia, regardless of whether heartburn is elicited by GER or esophageal stasis. Endoscopic examination can readily differentiate these disorders in most cases, although manometry may sometimes be required to make the distinction in equivocal cases. Readers may find interest in the AGA's recent technical review of the clinical uses of esophageal manometry and detailed descriptions of the procedure. Esophageal manometry is the gold standard test for esophageal motility disorders [23]. Esophageal manometry has been shown to be especially useful for definitively diagnosing achalasia or diffuse esophageal spasm and for detecting esophageal motor abnormalities associated with collagen-vascular disease.

(a) Fluid‐filled esophagus (b) Dilated esophagus

**Figure 2.** Achalasia

therapy. Esophagogastroduodenoscopy usually reveals large solitary ulcers or erosions in

A patient with a usual history of caustic substance ingestion and prolonged hospitalization for severe caustic damage was hospitalized again because of an increase in dysphagia and odynophagia [19]. The gold standard of safely assessing the depth, extent of caustic ingestion injury, and appropriate therapeutic regimen is EGD. The patients underwent EGD within 24 hours of admission and mucosal damage was graded using Zagar's modified endoscopic

Radiation therapy (RT), the primary modality for patients with tumors of the upper aerodigestive tract, allows larynx preservation [20]. Proximal esophageal strictures occur in 2–16% of patients after radiation therapy for cancers of the lung or head and neck. RT-induced laryngeal edema (due to inflammation and lymphatic disruption) is a common and expected side effect. Progressive edema and associated fibrosis detected by endoscope or barium swallowing can lead to long-term problems with phonation and swallowing. Aspiration pneumonia associated with dysphagia after intensive chemo radiation therapy has recently

Drug-induced esophagitis mainly presents as chest pain, odynophagia, and dysphagia. In the agents known to induce esophagitis, antibiotics are the most common culprit. Other causative agents include nonsteroidal anti-inflammatory drugs, antihypertensive drugs, acetamino‐ phen, oral hypoglycemic agents (glimepiride), bisphosphonates (alendronate, ibandronate), ascorbic acid, and warfarin [21]. The most frequent endoscopic site of drug-induced esopha‐ gitis is the middle third of the esophagus. On endoscopy, drug-induced esophagitis manifests as ulcers of various forms such as kissing ulcers, erosions, or ulcers with bleeding, as patchy sections coated with drug materials or impacted pill fragments, or sometimes as strictures.

Achalasia is regarded as a disease exclusively involving the smooth muscle. About 70–80% of patients have absent or incomplete lower esophageal sphincter (LES) relaxation with wet swallows, while the remainder have complete but shortened relaxation [22]. The typical endoscopic findings are shown in Figure 2A,B. Patients with esophageal stasis are often unaware of this condition. Heartburn, though not infrequent, bears little relationship to the esophageal acid exposure in achalasia, regardless of whether heartburn is elicited by GER or esophageal stasis. Endoscopic examination can readily differentiate these disorders in most cases, although manometry may sometimes be required to make the distinction in equivocal cases. Readers may find interest in the AGA's recent technical review of the clinical uses of esophageal manometry and detailed descriptions of the procedure. Esophageal manometry is the gold standard test for esophageal motility disorders [23]. Esophageal manometry has been shown to be especially useful for definitively diagnosing achalasia or diffuse esophageal spasm and for detecting esophageal motor abnormalities associated with collagen-vascular disease.

**2.6. Esophagitis induced by caustic injury, radiation injury, or drugs**

the distal esophagus.

96 Seminars in Dysphagia

classification scheme [19].

**2.7. Achalasia**

been reported at a growing frequency.

#### **2.8. Diffuse esophageal spasm**

Diffuse esophageal spasm (DES) is an uncommon disorder characterized by an impairment of ganglionic inhibition in the distal esophagus. Upper endoscopy should be performed as an initial evaluation of esophageal symptoms consistent with spastic disorders [24]. No specific endoscopic abnormality appears in most cases, but the endoscopist may notice disordered esophageal contractions. DES is defined by the presence of simultaneous contractions on conventional manometry. In higher resolution recordings by HRM with EPT, however, the propagation velocity varies greatly along the length of the esophagus and often progresses rapidly in some regions. Esophageal manometry, the putative gold standard in the diagnosis of achalasia, classically shows aperistalsis and failure of relaxation of the lower esophageal sphincter.

#### **2.9. Extrinsic compression**

Dysphagia is also caused by extrinsic compression of the esophagus associated with media‐ stinal diseases, tumors such as lung cancer and lymphoma, or infections such as tuberculosis or histoplasmosis [1,3].
