2417 Gastrointestinal Endoscopy CHAPTER 322

FIGURE 322-53 Peptic esophageal stricture associated with esophagitis.

FIGURE 322-54 Schatzki’s ring at the gastroesophageal junction.

FIGURE 322-55 Eosinophilic esophagitis. Multiple circular rings of the esophagus

creating a corrugated appearance and an impacted grape at the narrowed

esophagogastric junction. The diagnosis requires biopsy with histologic finding of

>15–20 eosinophils/high-power field.

and family history. Individuals with inflammatory bowel disease, a history of colorectal polyps or cancer, family members with adenomatous

polyps or cancer, or certain familial cancer syndromes (Fig. 322-64)

are at increased risk for colorectal cancer. An individual without these

factors is generally considered at average risk.

Screening strategies are summarized in Table 322-3. While fecal

immunochemical tests (FIT) for heme or stool tests for occult blood

have been shown to decrease the mortality rate from colorectal cancer,

they do not detect some cancers and many polyps. FIT-DNA multitargeted stool DNA tests appear to be more sensitive, but direct visualization of the colon is the gold standard method for detection of polyps

and cancers and remains a preferred screening strategy. Sigmoidoscopy

is also used for colorectal cancer screening. However, the distribution

of colon cancers has changed in the United States over time, with

proportionally fewer rectal and left-sided cancers than in the past.

Large American studies of colonoscopy for screening of average-risk

individuals show that cancers are roughly equally distributed between

the left and right colon and half of patients with right-sided lesions

have no polyps in the left colon. Visualization of the entire colon thus

appears to be the optimal strategy for colorectal cancer screening and

prevention.

Computed tomography colonography (CTC) is a radiologic technique that images the colon with CT following rectal insufflation of

the colonic lumen. Computer rendering of CT images generates an

electronic display of a virtual “flight” along the colonic lumen, simulating colonoscopy (Fig. 322-65). Findings detected during CTC often

require subsequent conventional colonoscopy for confirmation and

treatment.

■ DIARRHEA

Most cases of diarrhea are acute, self-limited, and due to infections or

medication. Chronic diarrhea (lasting >6 weeks) is more often due to a

primary inflammatory, malabsorptive, or motility disorder; is less likely

to resolve spontaneously; and generally requires diagnostic evaluation.

Patients with chronic diarrhea or severe, unexplained acute diarrhea

often undergo endoscopy if stool tests for pathogens are unrevealing.

The choice of endoscopic testing depends on the clinical setting.

Patients with colonic symptoms and findings such as bloody

diarrhea, tenesmus, fever, or leukocytes in stool generally undergo

sigmoidoscopy or colonoscopy to assess for colitis (Fig. 322-9). Sigmoidoscopy is an appropriate initial test in most patients. Conversely,

patients with symptoms and findings suggesting small-bowel disease,

with occult blood in the stool should undergo colonoscopy to diagnose

or exclude colorectal neoplasia, especially if they are >50 years old or

have a family history of colonic neoplasia. Whether upper endoscopy

is also indicated depends on the patient’s symptoms.

The small intestine may be the source of chronic intestinal bleeding,

especially if colonoscopy and upper endoscopy are not diagnostic.

The utility of small-bowel evaluation varies with the clinical setting

and is most important in patients in whom bleeding causes chronic

or recurrent anemia. In contrast to the low diagnostic yield of smallbowel radiography, positive findings on capsule endoscopy are seen in

50–70% of patients with suspected small-intestinal bleeding. The most

common finding is mucosal vascular ectasia. CT and MR enterography

accurately detect small-bowel masses and Crohn’s disease and are also

useful for initial small-bowel evaluation. Deep enteroscopy may follow

capsule endoscopy for biopsy of lesions or to provide specific therapy,

such as argon plasma coagulation of vascular ectasias (Fig. 322-63).

■ COLORECTAL CANCER SCREENING

The majority of colon cancers develop from preexisting colonic adenomas, and colorectal cancer can be largely prevented by the detection

and removal of adenomatous polyps (Video V5-24). The choice of

screening strategy for an asymptomatic person depends on personal

2418 PART 10 Disorders of the Gastrointestinal System

C D

C

FIGURE 322-57 Endoscopic management of peptic stricture. A. Peptic stricture. B. Through-the-scope balloon dilation of stricture. C. Improvement in luminal diameter after dilation.

A

FIGURE 322-56 Zenker’s diverticulum. A. Contrast esophagography demonstrates a moderate-sized Zenker’s diverticulum. B. Endoscopic view of the Zenker’s diverticulum

(left) relative to the true esophageal lumen (right) separated by the diverticular septum. C. Flexible endoscopic diverticulotomy using an electrosurgical knife. D. Appearance

post diverticulotomy.

B

A B

2419 Gastrointestinal Endoscopy CHAPTER 322

A B C

A B

FIGURE 322-58 Endoscopic management of an esophagogastric anastomotic stricture. A. Recurrent anastomotic stricture despite periodic balloon dilation. B. Needle-knife

electroincision of stricture. C. Improvement in luminal opening after therapy.

FIGURE 322-59 Palliation of malignant dysphagia. A. Obstructing distal esophageal cancer. B. Palliative stent placement.

such as large-volume watery stools, substantial weight loss, and malabsorption of iron, calcium, or fat, may undergo upper endoscopy with

duodenal aspirates for assessment of bacterial overgrowth and biopsies

for assessment of mucosal diseases, such as celiac sprue.

Many patients with chronic diarrhea do not fit either of these patterns. In the setting of a long-standing history of alternating constipation and diarrhea dating to early adulthood, without findings such as

blood in the stool or anemia, a diagnosis of irritable bowel syndrome

may be made without direct visualization of the bowel. Steatorrhea and

upper abdominal pain may prompt evaluation of the pancreas rather

than the gut. Patients whose chronic diarrhea is not easily categorized

often undergo initial colonoscopy to examine the entire colon and

terminal ileum for inflammatory or neoplastic disease (Fig. 322-66).

■ MINOR HEMATOCHEZIA

Bright red blood passed with or on formed brown stool usually has an

anal, rectal, or sigmoid source (Fig. 322-67). Even trivial amounts of

hematochezia should be investigated with colonoscopy and/or flexible

sigmoidoscopy together with anoscopy to exclude polyps or cancers,

especially in patients >40 years old and those with a personal or family

history of colorectal polyps or cancer. Patients reporting red blood

on the toilet tissue only, without blood in the toilet or on the stool,

are generally bleeding from a lesion in the anal canal; careful external

inspection, digital examination, and sigmoidoscopy with anoscopy

may be sufficient for diagnosis in such cases.

■ PANCREATITIS

About 20% of patients with pancreatitis have no identified cause

after routine clinical investigation (including a review of medication

and alcohol use; measurement of serum triglyceride, calcium, and

immunoglobulin G subclass 4 levels; abdominal ultrasonography; and

CT or MRI). Endoscopic assessment leads to a specific diagnosis in the

majority of such patients, often altering clinical management. Endoscopic investigation is particularly appropriate if the patient has had

more than one episode of pancreatitis.

Microlithiasis, or the presence of microscopic crystals in bile, is

a leading cause of previously unexplained acute pancreatitis and is

sometimes seen during abdominal ultrasonography as layering sludge

or flecks of floating, echogenic material in the gallbladder. EUS may

identify previously undetected microlithiasis.

Previously undetected chronic pancreatitis, pancreatic malignancy,

or pancreas divisum may be diagnosed by either ERCP or EUS. Autoimmune pancreatitis is often suspected based on CT, MRI, or serologic

findings, but it may first become apparent during EUS and may require

EUS-guided pancreatic biopsy for histologic diagnosis.

Severe pancreatitis often results in pancreatic fluid collections.

Symptomatic pseudocysts and areas of walled-off pancreatic necrosis can be drained into the stomach or duodenum endoscopically,

using transpapillary and transmural endoscopic techniques. Pancreatic

necrosis can be debrided by direct endoscopic necrosectomy (Video

V5-2) via an endoscopically created transmural drainage site.

■ CANCER STAGING

Local staging of esophageal, gastric, pancreatic, bile duct, and rectal

cancers can be obtained with EUS (Fig. 322-20). EUS with fine-needle

aspiration (Fig. 322-21) currently provides the most accurate preoperative assessment of local tumor and nodal staging, but it does not detect

many distant metastases. Details of the local tumor stage can guide

treatment decisions including resectability and need for neoadjuvant

2420 PART 10 Disorders of the Gastrointestinal System

A B

C D

FIGURE 322-60 Placement of biliary and duodenal self-expanding metal stents (SEMS) for obstruction caused by pancreatic cancer. A. Endoscopic retrograde

cholangiopancreatography (ERCP) demonstrates a distal bile duct stricture (arrow). B. A biliary SEMS is placed. C. Contrast injection demonstrates a duodenal stricture

(arrow). D. Biliary and duodenal SEMS in place.

FIGURE 322-61 Celiac sprue. Scalloped duodenal folds in a patient with celiac

sprue.

FIGURE 322-62 Capsule endoscopy. Images of a mildly scalloped jejunal fold

(left) and an ileal tumor (right) in a patient with celiac sprue. (Images courtesy of

Dr. Elizabeth Rajan; with permission.)

therapy. EUS with transesophageal needle biopsy may also be used to

assess the presence of non-small-cell lung cancer in mediastinal nodes.

OPEN-ACCESS ENDOSCOPY

Direct scheduling of endoscopic procedures by primary care physicians without preceding gastroenterology consultation, or openaccess endoscopy, is common. When the indications for endoscopy

are clear-cut and appropriate, the procedural risks are low, and the

patient understands what to expect, open-access endoscopy streamlines patient care and decreases costs.

2421 Gastrointestinal Endoscopy CHAPTER 322

FIGURE 322-63 Small-bowel vascular ectasia. A. Actively bleeding mid-jejunal vascular ectasia identified by double-balloon enteroscopy. B. Ablation of vascular ectasia

with argon plasma coagulation (APC). C. Hemostasis secured following APC.

A B

C

FIGURE 322-64 Familial adenomatous polyposis. Numerous colon polyps in a

patient with familial adenomatous polyposis syndrome.

Patients referred for open-access endoscopy should have a recent

history, physical examination, and medication list that are available

for review when the patient comes to the endoscopy suite. Patients

with unstable or symptomatic cardiovascular or respiratory conditions

should not be referred directly for open-access endoscopy. Those with

particular conditions who are undergoing certain procedures should be

prescribed prophylactic antibiotics prior to endoscopy (Table 322-1).

In addition, patients taking anticoagulants and/or antiplatelet drugs

may require adjustment of these agents before endoscopy based on the

procedural risk for bleeding and their underlying risk for a thromboembolic event (Table 322-2).

Common indications for open-access EGD include dyspepsia resistant to a trial of appropriate therapy, dysphagia, gastrointestinal bleeding, and persistent anorexia or early satiety. Open-access colonoscopy

is often requested in men or postmenopausal women with irondeficiency anemia, in patients with hematochezia or occult blood

in the stool, in patients with a previous history of colorectal adenomatous polyps or cancer, and for colorectal cancer screening.

Flexible sigmoidoscopy is commonly performed as an open-access

procedure.

2422 PART 10 Disorders of the Gastrointestinal System

TABLE 322-3 Colorectal Cancer Screening Strategies

CHOICES/RECOMMENDATIONS COMMENTS

Average-Risk Patients

Asymptomatic individuals ≥45 years old Colonoscopy every 10 yearsa Preferred cancer prevention strategy

Multitargeted stool DNA test every 3 years

Annual FIT or FOBT, multiple take-home specimen cards, with or

without sigmoidoscopy every 5–10 years

Less sensitive than colonoscopy; colonoscopy if

results are positive

Does not detect many polyps; colonoscopy if results

are positive

CT colonography every 5 years Colonoscopy if results are positive

Flexible sigmoidoscopy every 5 years Does not detect proximal colon polyps and cancers;

colonoscopy if an adenomatous polyp is found

Personal History of Polyps or CRC

1–2 small (<1 cm) adenomas with low-grade

dysplasia

Repeat colonoscopy in 5–10 yearsa Assuming complete polyp resection. Interval may

vary based on prior personal history and family

history

3–10 adenomas, or any high-risk adenomab Repeat colonoscopy in 3 yearsa

; subsequent colonoscopy based

on findings

Assuming complete polyp resection

>10 adenomas Repeat colonoscopy in <3 years based on clinical judgmenta Consider evaluation for FAP or HNPCC; see

recommendations below

Piecemeal removal of a sessile polyp Exam in 2–6 months to verify complete removal

Small (<1 cm) hyperplastic polyps of sigmoid

and rectum

Repeat colonoscopy in 10 yearsa Those with hyperplastic polyposis syndrome merit

more frequent follow-up

Sessile serrated adenoma/polyp <10 mm,

without dysplasia

Sessile serrated adenoma/polyp ≥10 mm or

with dysplasia, or ≥2 serrated polyps

Repeat colonoscopy in 5 yearsa

Repeat colonoscopy in 3 yearsa Serrated polyposis syndrome merits more frequent

follow-up

Incompletely removed serrated polyp ≥1 cm Exam in 2–6 months to verify complete removal

Colon cancer Evaluate entire colon around the time of resection, then repeat

colonoscopy in 1 yeara

Subsequent colonoscopy in 3 years if the 1-year

examination is normal

Inflammatory Bowel Disease

Long-standing (>8 years) ulcerative pancolitis

or Crohn’s colitis, or left-sided ulcerative

colitis of >15 years’ duration

Colonoscopy with biopsies every 1–2 years Consider chromoendoscopy or other advanced

imaging techniques for detection of flat dysplasia

during colonoscopy

Family History of Polyps or CRC

First-degree relatives with only small tubular

adenomas

Same as average risk

One first-degree relative with CRC or

advanced adenoma at age ≥60 years

Colonoscopy every 10 years starting at age 40

One first-degree relative with CRC or

advanced adenoma at age <60 years, or two

first-degree relatives with CRC or advanced

adenomas at any age

Colonoscopy every 5 years beginning at age 40 years or 10 years

younger than age at diagnosis of the youngest affected relative,

whichever is earlier

Familial adenomatous polyposis (FAP) Sigmoidoscopy or colonoscopy annually, beginning at age

10–12 years

Consider genetic counseling and testing; consider

screening family members

Hereditary nonpolyposis colorectal cancer

(HNPCC; Lynch syndrome)

Serrated polyposis syndrome (SPS)

Colonoscopy every 2 years beginning at age 20–25 years (or 10

years younger than the youngest first-degree relative was when

diagnosed with CRC) until age 40, then annually thereafter

Colonoscopy at age 40 (or the same age at which the youngest

first-degree relative was when diagnosed with SPS, or 10 years

younger than the youngest first-degree relative was when

diagnosed with CRC), then every 1–2 years thereafter

Consider histologic evaluation for microsatellite

instability in tumor specimens of patients who

meet modified Bethesda criteria; consider genetic

counseling and testing, consider screening family

members

Consider screening family members, even of patients

with multiple serrated polyps who do not meet SPS

criteria.

a

Assumes good colonic preparation and complete examination to cecum. b

High-risk adenoma: any adenoma ≥1 cm in size or containing high-grade dysplasia or villous

features.

Abbreviations: CRC, colorectal cancer; FIT, fecal immunochemical test; FOBT, fecal occult blood test.

Sources: Adapted from U.S. Preventative Services Task Force Draft Guidelines released in 2020 (https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/

colorectal-cancer-screening) and American Cancer Society Guidelines (https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/acsrecommendations.html), both accessed on December 12, 2020. See also G Mankaney et al: Serrated polyposis syndrome. Clin Gastroenterol Hepatol 18:777, 2020.

When patients are referred for open-access colonoscopy, the

primary care provider may need to choose a colonic preparation.

Commonly used oral preparations include polyethylene glycol lavage

solution, with or without citric acid. A “split-dose” regimen improves

the quality of colonic preparation. Osmotic purgative preparations

(such as sodium phosphate) are also effective but may cause fluid and

electrolyte abnormalities and renal toxicity, especially in patients with

renal failure or congestive heart failure and those >70 years of age.

2423 Diseases of the Esophagus CHAPTER 323

FIGURE 322-65 Virtual colonoscopy image of a colon polyp (arrow). (Image

courtesy of Dr. Jeff Fidler; with permission.)

FIGURE 322-66 Crohn’s ileitis. Edema, erythema, ulcers, and exudates involving the

terminal ileum.

FIGURE 322-67 Internal hemorrhoids with bleeding stigmata (arrow) as seen on

retroflexed view of the rectum.

■ FURTHER READING

ASGE Standards of Practice Committee et al: Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 81:81, 2015.

ASGE Standards of Practice Committee et al: Open-access endoscopy. Gastrointest Endosc 81:1326, 2015.

Barkun AN et al: Management of nonvariceal upper gastrointestinal

bleeding: Guideline recommendations from the international consensus group. Ann Intern Med 171:805, 2019.

Garcia-Tsao G et al: Portal hypertensive bleeding in cirrhosis: Risk

stratification, diagnosis, and management: 2016 practice guidance by

the American Association for the Study of Liver Diseases. Hepatology

65:310, 2017.

Rex DK et al: Colorectal cancer screening: Recommendations for

physicians and patients from the U.S. Multi-Society Task Force on

Colorectal Cancer. Gastroenterology 153:307, 2017.

Shaheen NJ et al: ACG clinical guideline: Diagnosis and management

of Barrett’s esophagus. Am J Gastroenterol 111:30, 2016.

Strate LL et al: ACG clinical guideline: Management of patients with

acute lower gastrointestinal bleeding. Am J Gastroenterol 111:459,

2016.

323 Diseases of the

Esophagus

Peter J. Kahrilas, Ikuo Hirano

ESOPHAGEAL STRUCTURE AND FUNCTION

The esophagus is a hollow, muscular tube coursing through the posterior mediastinum joining the hypopharynx to the stomach with a

sphincter at each end. It functions to transport food and fluid between

these ends, otherwise remaining empty. The physiology of swallowing,

esophageal motility, and oral and pharyngeal dysphagia are described

in Chap. 44. Esophageal diseases can be manifested by impaired function or pain. Key functional impairments are swallowing disorders and

excessive gastroesophageal reflux. Pain, sometimes indistinguishable

from cardiac chest pain, can result from inflammation, infection, dysmotility, or neoplasm.

SYMPTOMS OF ESOPHAGEAL DISEASE

The clinical history remains central to the evaluation of esophageal

symptoms. A thoughtfully obtained history will often expedite management. Important details include weight gain or loss, gastrointestinal

bleeding, dietary habits including the timing of meals, smoking, and

alcohol consumption. The major esophageal symptoms are heartburn, regurgitation, chest pain, dysphagia, odynophagia, and globus

sensation.

Heartburn (pyrosis), the most common esophageal symptom, is

characterized by a discomfort or burning sensation behind the sternum

that arises from the epigastrium and may radiate toward the neck.

Heartburn is an intermittent symptom, most commonly experienced

after eating, during exercise, and while lying recumbent. The discomfort is relieved with drinking water or taking an antacid but can occur

frequently, interfering with normal activities including sleep. The

association between heartburn and gastroesophageal reflux disease

(GERD) is so strong that empirical therapy for GERD has become

accepted management. However, the term heartburn is often misused

and/or referred to using other terms such as indigestion or repeating,

making it important to clarify the intended meaning.

Regurgitation is the effortless return of food or fluid into the pharynx without nausea or retching. Patients report a sour or burning fluid

in the throat or mouth that may also contain undigested food particles. Bending, belching, or maneuvers that increase intraabdominal

2424 PART 10 Disorders of the Gastrointestinal System

pressure can provoke regurgitation. A clinician needs to discriminate

among regurgitation, vomiting, and rumination. Vomiting is preceded

by nausea and accompanied by retching. Rumination is a behavior in

which recently swallowed food is regurgitated and then reswallowed

repetitively for up to an hour. Although there is some linkage between

rumination and cognitive deficiency, the behavior is also exhibited by

unimpaired individuals.

Chest pain is a common esophageal symptom with characteristics

similar to cardiac pain, sometimes making this distinction difficult.

Esophageal pain is usually experienced as a pressure-type sensation in

the mid chest, radiating to the mid back, arms, or jaws. The similarity

to cardiac pain is likely because the two organs share a nerve plexus

and the nerve endings in the esophageal wall have poor discriminative

ability among stimuli. Esophageal distention or even chemostimulation

(e.g., with acid) will often be perceived as chest pain. Gastroesophageal

reflux is the most common cause of esophageal chest pain.

Esophageal dysphagia (Chap. 44) is often described as a feeling of

food “sticking” or even lodging in the chest. Important distinctions are

between uniquely solid food dysphagia as opposed to liquid and solid,

episodic versus constant dysphagia, and progressive versus static dysphagia. If the dysphagia is for liquids as well as solid food, it suggests

a motility disorder such as achalasia. Conversely, uniquely solid food

dysphagia is suggestive of a stricture, ring, or tumor. Of note, a patient’s

localization of food hang-up in the esophagus is notoriously imprecise.

Approximately 30% of distal esophageal obstructions are perceived

as cervical dysphagia. In such instances, the absence of concomitant

symptoms generally associated with oropharyngeal dysphagia such as

aspiration, nasopharyngeal regurgitation, cough, drooling, or obvious

neuromuscular compromise should suggest an esophageal etiology.

Odynophagia is pain either caused by or exacerbated by swallowing.

Although typically considered distinct from dysphagia, odynophagia

may manifest concurrently with dysphagia. Odynophagia is more

common with pill or infectious esophagitis than with reflux esophagitis

and should prompt a search for these entities. When odynophagia does

occur in GERD, it is likely related to an esophageal ulcer or extensive

erosions.

Globus sensation, also known as globus pharyngeus, is the perception of a lump or fullness in the throat that is felt irrespective of

swallowing. Although such patients are frequently referred for an

evaluation of dysphagia, globus sensation is often relieved by the act

of swallowing. As implied by its alternative name, “globus hystericus,”

globus sensation often occurs in the setting of anxiety or obsessivecompulsive disorders. Clinical experience teaches that it is often attributable to GERD.

Water brash is excessive salivation resulting from a vagal reflex triggered by acidification of the esophageal mucosa. This is not a common

symptom. Afflicted individuals will describe the unpleasant sensation

of the mouth rapidly filling with salty thin fluid, often in the setting of

concomitant heartburn.

DIAGNOSTIC STUDIES

■ ENDOSCOPY

Endoscopy, also known as esophagogastroduodenoscopy (EGD), is

the most useful test for the evaluation of the proximal gastrointestinal tract. Modern instruments produce high-quality, color images of

the esophageal, gastric, and duodenal lumen. Endoscopes also have

an instrumentation channel through which biopsy forceps, injection

catheters for local delivery of therapeutic agents, balloon dilators, or

devices for hemostasis or removal of mucosal lesions can be used. The

key advantages of endoscopy over barium radiography are as follows:

(1) increased sensitivity for the detection of mucosal lesions; (2) vastly

increased sensitivity for the detection of abnormalities mainly identifiable by color, such as Barrett’s metaplasia or vascular lesions; (3)

the ability to obtain biopsy specimens for histologic examination of

suspected abnormalities; and (4) the ability to dilate strictures during

the examination. Submucosal endoscopy has emerged as a diagnostic

modality for assessment of subepithelial lesions and therapy of esophageal motility disorders. The main disadvantages of endoscopy are low

sensitivity for detection of diffuse, nonfocal esophageal strictures, cost,

and the need for sedatives or anesthetics.

■ RADIOGRAPHY

Contrast radiography of the esophagus, stomach, and duodenum

can demonstrate reflux of the contrast media, hiatal hernia, mucosal

granularity, erosions, ulcerations, and strictures. The sensitivity of

radiography compared with endoscopy for detecting reflux esophagitis

reportedly ranges from 22 to 95%, with higher grades of esophagitis

(i.e., ulceration or stricture) exhibiting greater detection rates. Conversely, the sensitivity of barium radiography for detecting esophageal

strictures is greater than that of endoscopy, especially when the study

is done in conjunction with a 13-mm barium tablet. Barium studies

also provide an assessment of esophageal function and morphology

that may be undetected on endoscopy. Tracheoesophageal fistula,

altered postsurgical anatomy, and extrinsic esophageal compression

are conditions where radiographic imaging complements endoscopic

assessment. Hypopharyngeal pathology and disorders of the cricopharyngeus muscle are better appreciated on radiographic examination than with endoscopy, particularly with rapid sequence or video

fluoroscopic recording. The major shortcoming of barium radiography

is that it rarely obviates the need for endoscopy. Either a positive or

a negative study is usually followed by an endoscopic evaluation to

obtain biopsies, provide therapy, or clarify findings in the case of a

positive examination or to add a level of certainty in the case of a negative examination.

■ ENDOSCOPIC ULTRASOUND

Endoscopic ultrasound (EUS) instruments combine an endoscope with

an ultrasound transducer to create a transmural image of the tissue surrounding the endoscope tip. The key advantage of EUS over alternative

radiologic imaging techniques is much greater resolution attributable

to the proximity of the ultrasound transducer to the area being examined. Available devices can provide either radial imaging (360-degree,

cross-sectional) or a curved linear image that can guide fine-needle

aspiration of imaged structures such as lymph nodes or tumors. Major

esophageal applications of EUS are to stage esophageal cancer, to evaluate dysplasia in Barrett’s esophagus, and to assess submucosal lesions.

■ ESOPHAGEAL MANOMETRY

Esophageal manometry, or motility testing, entails positioning a

pressure-sensing catheter within the esophagus and then observing the

contractility following test swallows. The upper esophageal sphincter

and lower esophageal sphincter (LES) appear as zones of high pressure that relax on swallowing, whereas the intersphincteric esophagus

exhibits peristaltic contractions. Manometry is used to diagnose motility disorders (achalasia, diffuse esophageal spasm [DES]) and to assess

peristaltic integrity prior to the surgery for reflux disease. Technologic

advances have enhanced esophageal manometry as high-resolution

esophageal pressure topography (Fig. 323-1). Manometry can also

be combined with intraluminal impedance monitoring. Impedance

recordings use a series of paired electrodes added to the manometry

catheter. Esophageal luminal contents in contact with the electrodes

decrease (liquid) or increase (air) the impedance signal, allowing

detection of anterograde or retrograde esophageal bolus transit.

■ REFLUX TESTING

GERD is often diagnosed in the absence of endoscopic signs of esophagitis, which would otherwise define the disease. This occurs in the

settings of partially treated disease, an abnormally sensitive esophageal

mucosa, or, most commonly, in nonerosive reflux disease. In such

instances, reflux testing can demonstrate excessive esophageal exposure to refluxed gastric fluid, the physiologic abnormality of GERD.

This can be done by ambulatory 24- to 96-h esophageal pH recording

using either a wireless pH-sensitive transmitter that is affixed to the

esophageal mucosa or a transnasally positioned wire electrode with

the tip stationed in the distal esophagus. Either way, the outcome is

expressed as the percentage of the day that the pH was <4 (indicative

of recent acid reflux), with values exceeding 5% indicative of GERD.

Reflux testing is useful in the evaluation of patients presenting with

2425 Diseases of the Esophagus CHAPTER 323

atypical symptoms or an inexplicably poor response to therapy. Intraluminal impedance monitoring can be added to pH monitoring to detect

reflux events irrespective of whether or not they are acidic, potentially

increasing the sensitivity of the study.

STRUCTURAL DISORDERS

■ HIATAL HERNIA

Hiatal hernia is a herniation of viscera, most commonly the stomach,

into the mediastinum through the esophageal hiatus of the diaphragm.

Four types of hiatal hernia are distinguished, with type I, or sliding hiatal hernia, composing at least 95% of the overall total. A sliding hiatal

hernia is one in which the gastroesophageal junction and gastric cardia

translocate cephalad as a result of weakening of the phrenoesophageal

ligament attaching the gastroesophageal junction to the diaphragm at

the hiatus and dilatation of the diaphragmatic hiatus. The incidence

of sliding hernia increases with age. True to its name, sliding hernias

enlarge with increased intraabdominal pressure, swallowing, and respiration. Conceptually, sliding hernias are the result of wear and tear:

increased intraabdominal pressure from abdominal obesity, pregnancy,

etc., along with hereditary factors predisposing to the condition. The

main significance of sliding hernias is the propensity of affected individuals to have GERD.

Type II, III, and IV hiatal hernias are all subtypes of paraesophageal

hernia in which the herniation into the mediastinum includes a visceral

structure other than the gastric cardia. With type II and III paraesophageal hernias, the gastric fundus also herniates, with the distinction

being that in type II, the gastroesophageal junction remains fixed at

the hiatus, whereas type III is a combined sliding and paraesophageal

hernia. With type IV hiatal hernias, viscera other than the stomach

herniate into the mediastinum, most commonly the colon. With

type II and III paraesophageal hernias, the stomach may twist as it

herniates, and large paraesophageal hernias can lead to an “upside

down stomach,” gastric volvulus, and even strangulation of the stomach. Because of this risk, surgical repair is often advocated for large

paraesophageal hernias, particularly when they are symptomatic.

■ RINGS AND WEBS

A lower esophageal mucosal ring, also called a B ring, is a thin membranous narrowing at the squamocolumnar mucosal junction (Fig. 323-2).

Its origin is unknown, but B rings are demonstrable in ~10–15% of the

general population and are usually asymptomatic. When the lumen

diameter is <13 mm, distal rings are usually associated with episodic

solid food dysphagia and are called Schatzki rings. Patients typically

present older than 40 years, consistent with an acquired rather than

congenital origin. Schatzki ring is one of the most common causes of

intermittent food impaction, also known as “steakhouse syndrome”

because meat is a typical instigator. Symptomatic rings are readily

treated by dilation.

Web-like constrictions higher in the esophagus can be of congenital or inflammatory origin. Asymptomatic cervical esophageal webs

are demonstrated in ~10% of people and typically originate along

the anterior aspect of the esophagus. Depending on the degree of

impingement, they can cause intermittent dysphagia to solids similar to

Schatzki rings and are similarly treated with dilation. The combination

of symptomatic proximal esophageal webs and iron-deficiency anemia

in middle-aged women constitutes Plummer-Vinson or Paterson-Kelly

syndrome.

■ DIVERTICULA

Esophageal diverticula are categorized by location, with the most common being epiphrenic, hypopharyngeal (Zenker’s), and midesophageal. Epiphrenic and Zenker’s diverticula are false diverticula involving

herniation of the mucosa and submucosa through the muscular layer

of the esophagus. These lesions result from increased intraluminal

pressure associated with distal obstruction. In the case of Zenker’s, the

obstruction is a stenotic cricopharyngeus muscle (upper esophageal

sphincter), and the hypopharyngeal herniation most commonly occurs

in an area of natural weakness proximal to the cricopharyngeus known

FIGURE 323-1 High-resolution esophageal pressure topography (right) and conventional manometry (left) of a normal swallow. E, esophageal body; LES, lower esophageal

sphincter; UES, upper esophageal sphincter.

Sliding hiatal

hernia

Rugal folds

traversing hiatus

Diaphragmatic

impression

B ring

squamo-columnar

junction

A ring

Phrenic

ampulla

Esophageal

vestibule

Tubular

esophagus

FIGURE 323-2 Radiographic anatomy of the gastroesophageal junction.

2426 PART 10 Disorders of the Gastrointestinal System

as Killian’s triangle (Fig. 323-3). Small Zenker’s diverticula are usually

asymptomatic, but when they enlarge sufficiently to retain food and

saliva, they can be associated with dysphagia, halitosis, and aspiration.

Treatment is by surgical diverticulectomy and cricopharyngeal myotomy or transoral, endoscopic marsupialization.

Epiphrenic diverticula are often associated with achalasia, esophageal hypercontractile disorders, or a distal esophageal stricture.

Midesophageal diverticula may be caused by traction from adjacent

inflammation (tuberculosis, histoplasmosis), in which case they are

true diverticula involving all layers of the esophageal wall, or by

pulsion associated with esophageal motor disorders. Midesophageal

and epiphrenic diverticula are often asymptomatic until they enlarge

sufficiently to retain food and cause dysphagia and regurgitation.

Symptoms attributable to the diverticula tend to correlate more with

the underlying esophageal disorder than the size of the diverticula.

Large diverticula can be removed surgically, usually in conjunction

with a myotomy if the underlying motility disorder is identified. Diffuse intramural esophageal pseudodiverticulosis is a rare entity that

results from dilatation of the excretory ducts of submucosal esophageal

glands (Fig. 323-4). Esophageal candidiasis and proximal esophageal

strictures are commonly found in association with this disorder.

■ TUMORS

Esophageal cancer occurs in ~4.5/100,000 people in the United States,

with the associated mortality being 3.9/100,000. It is ~10 times less

common than colorectal cancer but kills about one-quarter as many

patients. These statistics emphasize both the rarity and lethality of

esophageal cancer. One notable trend is the shift of dominant esophageal cancer type from squamous cell to adenocarcinoma, strongly

linked to reflux disease and Barrett’s metaplasia. Other distinctions

between cell types are the predilection for adenocarcinoma to affect

the distal esophagus in white males and for squamous cell carcinoma to

affect the more proximal esophagus in black males with the added risk

factors of smoking, alcohol consumption, caustic injury, and human

papillomavirus infection (Chap. 80).

The typical presentation of esophageal cancer is of progressive solid

food dysphagia and weight loss. Associated symptoms may include

odynophagia, iron deficiency, cough from tracheoesophageal fistula,

and hoarseness from left recurrent laryngeal nerve injury. Generally,

respiratory symptoms are manifestations of locally invasive or even

metastatic disease. Even when detected as a small lesion, esophageal

cancer has poor survival because of the abundant esophageal lymphatics leading to regional lymph node metastases.

Benign esophageal tumors are uncommon and usually discovered

incidentally. They include gastrointestinal stromal tumors, leiomyoma,

fibrovascular polyps, squamous papilloma, granular cell tumors, lipomas, mesenchymal neoplasms, and inflammatory fibroid polyps.

CONGENITAL ANOMALIES

The most common congenital esophageal anomaly is esophageal

atresia, occurring in ~1 in 5000 live births. Atresia can occur in several

permutations, the common denominator being developmental failure

A B C

FIGURE 323-3 Examples of small (A) and large (B, C) Zenker’s diverticula arising from Killian’s triangle in the distal hypopharynx. Smaller diverticula are evident only

during the swallow, whereas larger ones retain food and fluid.

FIGURE 323-4 Intramural esophageal pseudodiverticulosis associated with

chronic obstruction. Invaginations of contrast into the esophageal wall outline deep

esophageal glands.

2427 Diseases of the Esophagus CHAPTER 323

of fusion between the proximal and distal esophagus associated with

a tracheoesophageal fistula, most commonly with the distal segment

excluded. Alternatively, there can be an H-type configuration in

which esophageal fusion has occurred, but with a tracheoesophageal

fistula. Esophageal atresia is usually recognized and corrected surgically within the first few days of life. Later life complications include

dysphagia from anastomotic strictures or absent peristalsis and reflux,

which can be severe. Less common developmental anomalies include

congenital esophageal stenosis, webs, and duplications.

Dysphagia can also result from congenital abnormalities that cause

extrinsic compression of the esophagus. In dysphagia lusoria, the

esophagus is compressed by an aberrant right subclavian artery arising

from the descending aorta and passing behind the esophagus. Alternatively, vascular rings may surround and constrict the esophagus.

Heterotopic gastric mucosa, also known as an esophageal inlet patch,

is a focus of gastric-type epithelium in the proximal cervical esophagus;

the estimated prevalence is 4–5%. The inlet patch is thought to result

from incomplete replacement of embryonic columnar epithelium with

squamous epithelium. The majority of inlet patches are asymptomatic,

but acid production can occur as most contain fundic-type gastric

epithelium with parietal cells.

ESOPHAGEAL MOTILITY DISORDERS

Esophageal motility disorders are diseases attributable to esophageal

neuromuscular dysfunction commonly associated with dysphagia,

chest pain, or heartburn. The major entities are achalasia, diffuse

esophageal spasm (DES), jackhammer esophagus, and GERD. Motility disorders can also be secondary to systemic disease processes, as

is the case with pseudoachalasia, Chagas’ disease, and scleroderma.

Not included in this discussion are diseases affecting the pharynx and

proximal esophagus, the impairment of which is almost always part of

a more global neuromuscular disease process.

■ ACHALASIA

Achalasia is a rare disease caused by loss of ganglion cells within the

esophageal myenteric plexus, with a population incidence estimated to

be 1–3 per 100,000 and presentation usually occurring between age 25

and 60 years. With long-standing disease, aganglionosis is noted. The

disease involves both excitatory (cholinergic) and inhibitory (nitric

oxide) ganglionic neurons. Functionally, inhibitory neurons mediate

deglutitive LES relaxation and the sequential propagation of peristalsis.

Their absence leads to impaired deglutitive LES relaxation and absent

peristalsis. Increasing evidence suggests that the ultimate cause of ganglion cell degeneration in achalasia is an autoimmune process attributable to a latent infection with human herpes simplex virus 1 combined

with genetic susceptibility.

Long-standing achalasia is characterized by progressive dilatation

and sigmoid deformity of the esophagus with hypertrophy of the

LES. Clinical manifestations may include dysphagia, regurgitation,

chest pain, and weight loss. Most patients report solid and liquid food

dysphagia. Regurgitation occurs when food, fluid, and secretions are

retained in the dilated esophagus. Patients with advanced achalasia are

at risk for bronchitis, pneumonia, or lung abscess from chronic regurgitation and aspiration. Chest pain may manifest early in the course of

achalasia. Patients describe a squeezing, pressure-like retrosternal pain,

sometimes radiating to the neck, arms, jaw, and back. Paradoxically,

some patients complain of heartburn that may be a chest pain equivalent. Treatment of achalasia is less effective at alleviating chest pain

than it is in relieving dysphagia or regurgitation.

The differential diagnosis of achalasia includes jackhammer esophagus, DES, Chagas’ disease, opioid-induced esophageal dysmotility,

and pseudoachalasia. Chagas’ disease is endemic in areas of central

Brazil, Venezuela, and northern Argentina and spread by the bite of

the reduviid (kissing) bug that transmits the protozoan Trypanosoma

cruzi. The chronic phase of the disease develops years after infection

and results from destruction of autonomic ganglion cells throughout

the body, including the heart, gut, urinary tract, and respiratory tract.

Manometric features of achalasia have been described in patients on

chronic opioids and may be confused with primary achalasia. Tumor

infiltration, most commonly seen with carcinoma in the gastric fundus

or distal esophagus, can also mimic primary achalasia. The resultant

“pseudoachalasia” accounts for up to 5% of suspected cases and is more

likely with advanced age, abrupt onset of symptoms (<1 year), and

weight loss. Hence, endoscopy is a necessary part of the evaluation of

achalasia. When the clinical suspicion for pseudoachalasia is high and

endoscopy nondiagnostic, computed tomography (CT) scanning or

EUS may be of value. Rarely, pseudoachalasia can result from a paraneoplastic syndrome with circulating antineuronal antibodies.

Achalasia is diagnosed by barium swallow x-ray and/or esophageal manometry. Endoscopy excludes tumors or benign mechanical

strictures of the esophagogastric junction. The barium swallow x-ray

appearance is of a dilated esophagus with poor emptying, an airfluid level, and tapering at the LES giving it a beak-like appearance

(Fig. 323-5). Occasionally, an epiphrenic diverticulum is observed. In

long-standing achalasia, the esophagus may assume a sigmoid configuration. The diagnostic criteria for achalasia with esophageal manometry are impaired LES relaxation and absent peristalsis. High-resolution

manometry has somewhat advanced this diagnosis; three subtypes of

achalasia are differentiated based on the pattern of pressurization in the

nonperistaltic esophagus (Fig. 323-6). Because manometry identifies

early disease before esophageal dilatation and food retention, it is the

most sensitive diagnostic test.

No method of preventing or “curing” achalasia is known. Therapy is

thus directed at reducing LES pressure so that gravity and esophageal

pressurization permit esophageal emptying. While peristalsis does not

recover, remnants of peristalsis masked by esophageal pressurization

and dilatation prior to therapy may be demonstrable following effective treatment. LES pressure can be reduced by pharmacologic therapy,

pneumatic balloon dilation, or LES myotomy by means of submucosal

endoscopy or laparoscopic surgery. Pharmacologic therapies are relatively ineffective but can be offered as temporizing therapies. Nitrates

or calcium channel blockers are administered before eating but should

be used with caution because of their effects on blood pressure. Botulinum toxin, injected into the LES under endoscopic guidance, inhibits

acetylcholine release from nerve endings and improves dysphagia in

about two-thirds of cases for at least 6 months. Sildenafil and alternative phosphodiesterase inhibitors effectively decrease LES pressure, but

practicalities limit their clinical use in achalasia.

The only durable therapies for achalasia are pneumatic dilation and

LES myotomy. Pneumatic dilation, with a reported efficacy ranging

from 32 to 98%, is an endoscopic technique using a noncompliant,

cylindrical balloon dilator positioned across the LES and inflated to

a diameter of 3–4 cm. The major complication is perforation, with a

reported incidence of 0.5–5%. The most common surgical procedure

for achalasia is laparoscopic Heller myotomy, usually performed in

conjunction with an antireflux procedure (partial fundoplication);

good to excellent results are reported in 62–100% of cases. A European

FIGURE 323-5 Achalasia with esophageal dilatation, tapering at the gastroesophageal

junction, and an air-fluid level within the esophagus. The example on the left shows

sigmoid deformity with very advanced disease.