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Section 1 Disorders of the Alimentary

Tract

Disorders of the Gastrointestinal System PART 10

321

ANATOMIC CONSIDERATIONS

The gastrointestinal (GI) tract extends from the mouth to the anus

and is composed of organs with distinct functions. Sphincters that

assist in gut compartmentalization separate the organs. The gut wall is

organized into distinct layers that contribute to regional activities. The

mucosa is a barrier to luminal contents or a site for fluid and nutrient

transfer. Smooth muscle in association with the enteric nervous system

mediates propulsion between regions. Many GI organs possess a serosal layer that provides a supportive foundation and permits external

input.

Interactions with other systems serve the needs of the gut and the

body. Pancreaticobiliary conduits deliver bile and enzymes into the

duodenum. The vascular supply is modulated by GI activity. Lymphatic

channels assist in gut immune activities. Intrinsic nerves provide the

controls for propulsion and fluid regulation. Extrinsic neural input

provides volitional or involuntary control that is specific for each gut

region.

FUNCTIONS OF THE GI TRACT

The GI tract serves two main functions—assimilating nutrients and

eliminating waste. In the mouth, food is processed, mixed with salivary

amylase, and delivered to the gut lumen. The esophagus propels the

bolus into the stomach; the lower esophageal sphincter prevents oral

reflux of gastric contents. The squamous esophageal mucosa protects

against significant diffusion or absorption. Aboral esophageal contractions coordinate with relaxation of the upper and lower esophageal

sphincters on swallowing.

The stomach triturates and mixes the food bolus with pepsin and

acid. Gastric acid also sterilizes the upper gut. The proximal stomach

serves a storage function by relaxing to accommodate the meal. Phasic

contractions in the distal stomach propel food residue against the pylorus, where it is ground and thrust proximally for further mixing before

it is emptied into the duodenum. The stomach secretes intrinsic factor

for vitamin B12 absorption.

Most nutrient absorption occurs in the small intestine. The mucosal

villus architecture provides maximal surface area for absorption and is

endowed with specialized enzymes and transporters. Triturated food

from the stomach mixes with pancreatic juice and bile in the duodenum. Pancreatic juice contains enzymes for nutrient digestion and

bicarbonate to optimize the pH for enzyme activation. Bile secreted

by the liver and stored in the gallbladder is essential for lipid digestion. The proximal intestine is optimized for rapid absorption of most

nutrients and minerals, whereas the ileum is better suited for absorbing

vitamin B12 and bile acids. Bile contains by-products of erythrocyte

degradation, toxins, medications, and cholesterol for fecal evacuation.

Intestinal motor function delivers indigestible residue into the colon

for processing. The ileocecal junction is a sphincter that prevents

coloileal reflux, reducing microbial density.

The colon prepares waste for evacuation. The mucosa dehydrates

the stool, reducing daily ileal volumes of 1000–1500 mL to 100–200 mL

expelled from the rectum. The colon possesses a dense bacterial colonization that ferments undigested carbohydrates and short-chain fatty

acids. The gut microbiome also modulates immune and physiologic

activity. Esophageal transit takes seconds, and times in the stomach and

small intestine range from minutes to a few hours, but colon propagation requires >1 day in most individuals. Colon contractions exhibit

a to-and-fro character that promotes fecal desiccation. The proximal

colon mixes and absorbs fluid, while the distal colon exhibits peristaltic

contractions and mass movements to expel the stool. The colon terminates in the anus, which possesses volitional and involuntary controls

to permit fecal retention until it can be released in a convenient setting.

EXTRINSIC MODULATION OF GUT

FUNCTION

GI function is modified by influences outside the gut. Unlike other

organs, the gut is in continuity with the outside environment. Protective mechanisms are vigilant against injury from foods, medications,

toxins, and microbes. Mucosal immune mechanisms include epithelial

and lamina propria lymphocytes and plasma cells supported by lymph

node chains to prevent noxious agents from entering the circulation.

Antimicrobial peptides secreted by Paneth cells defend against pathogens. Drugs and toxins absorbed into the bloodstream are filtered

and detoxified in the liver via the portal venous circulation. Although

intrinsic nerves control most basic gut activities, extrinsic neural input

modulates many functions. Many GI reflexes involve extrinsic vagus

or splanchnic nerve pathways. The brain-gut axis alters function in

regions not under volitional regulation. Stress can disrupt gut motor,

secretory, and sensory function.

OVERVIEW OF GI DISEASES

GI diseases develop as a result of abnormalities within or outside of the

gut and range in severity from those that produce mild symptoms and

no long-term morbidity to those with intractable symptoms or adverse

outcomes. Diseases may be localized to one organ or exhibit diffuse

involvement at many sites.

■ CLASSIFICATION OF GI DISEASES

GI diseases are manifestations of alterations in nutrient assimilation or

waste evacuation or in the activities supporting these main functions.

Impaired Digestion and Absorption Diseases of the stomach,

intestine, biliary tree, and pancreas can disrupt digestion and absorption. The most common maldigestion syndrome, lactase deficiency,

produces gas and diarrhea after ingesting dairy products and has no

adverse outcomes. Other intestinal enzyme deficiencies produce similar symptoms after consuming other simple sugars. Celiac disease,

bacterial overgrowth, infectious enteritis, Crohn’s ileitis, and radiation

damage, which affect digestion and/or absorption more diffusely,

produce anemia, dehydration, electrolyte disorders, or malnutrition.

Gastric hypersecretory conditions such as gastrinoma damage the

intestinal mucosa, impair pancreatic enzyme activation, and accelerate transit due to excess gastric acid. Benign or neoplastic biliary

obstruction impairs fat digestion. Impaired pancreatic enzyme release

in chronic pancreatitis or pancreatic cancer decreases intraluminal

digestion and can lead to malnutrition.

Altered Secretion Some GI diseases result from dysregulation

of gut secretion. Gastric acid hypersecretion occurs in gastrinoma,

G-cell hyperplasia, retained antrum syndrome, and some patients

with duodenal ulcers. Gastric acid is reduced in atrophic gastritis and

pernicious anemia. Inflammatory and infectious small-intestinal and

colonic diseases produce fluid loss through impaired absorption or

enhanced secretion. Common hypersecretory conditions that cause

diarrhea include acute bacterial or viral infection, chronic Giardia or

cryptosporidia infections, small-intestinal bacterial overgrowth, bile

salt diarrhea, microscopic colitis, and diabetic diarrhea. Less common

Approach to the Patient

with Gastrointestinal

Disease

William L. Hasler, Chung Owyang

2382 PART 10 Disorders of the Gastrointestinal System

causes include large colonic villus adenomas and endocrine neoplasias

with tumor overproduction of secretagogue transmitters such as vasoactive intestinal polypeptide.

Altered Gut Transit Impaired gut transit may result from mechanical obstruction. Esophageal occlusion most often is due to stricture

(due to acid exposure or eosinophilic esophagitis) or neoplasm. Gastric obstruction develops from ulcer disease or gastric cancer. Smallintestinal obstruction most commonly results from adhesions but also

occurs with Crohn’s disease, radiation- or drug-induced strictures, and

less likely malignancy. The most common cause of colonic obstruction

is colon cancer, although inflammatory strictures develop with inflammatory bowel disease (IBD), after certain infections such as diverticulitis, or with some drugs.

Retardation of propulsion can develop from altered motor function.

Achalasia is characterized by impaired esophageal body peristalsis and

incomplete lower esophageal sphincter relaxation. Gastroparesis is the

delay in gastric emptying of meals due to impaired gastric motility.

Intestinal pseudoobstruction is the disruption of small-bowel contractility due to enteric nerve or smooth-muscle injury. Slow-transit constipation results from diffusely impaired colon propulsion. Constipation

also is produced by outlet abnormalities such as rectal prolapse, intussusception, or dyssynergia—a failure of anal or puborectalis relaxation

upon attempted defecation.

Disorders of rapid propulsion are less common than those with

delayed transit. Rapid gastric emptying occurs with postvagotomy

dumping syndrome, gastric hypersecretion, and some cases of functional dyspepsia and cyclic vomiting syndrome. Exaggerated intestinal

or colonic motor patterns may be responsible for diarrhea in irritable

bowel syndrome (IBS). Accelerated transit with hyperdefecation is

noted in hyperthyroidism.

Immune Dysregulation Many inflammatory GI conditions are

consequences of altered gut immune function. Mucosal inflammation

in celiac disease results from dietary ingestion of gluten-containing

grains. Some patients with food allergy also exhibit altered immune

populations. Eosinophilic esophagitis and eosinophilic gastroenteritis are inflammatory disorders with prominent mucosal eosinophil

infiltration. Ulcerative colitis and Crohn’s disease are disorders that

produce mucosal injury primarily in the lower gut. The microscopic

colitides, lymphocytic and collagenous colitis, exhibit colonic subepithelial infiltrates without visible mucosal damage. Bacterial, viral,

and protozoal organisms produce ileitis or colitis in selected patients.

Alterations in the gut microbiome (termed dysbiosis) are proposed to

trigger IBD, celiac disease, and IBS flares and may be factors in oncogenesis in some cases of pancreatic cancer.

Impaired Gut Blood Flow Different GI regions are at variable

risk for ischemic damage from impaired blood flow. Rare cases of gastroparesis result from blockage of the celiac and superior mesenteric

arteries. More commonly encountered are intestinal and colonic ischemia that are consequences of arterial embolus, arterial thrombosis,

venous thrombosis, or hypoperfusion from dehydration, sepsis, hemorrhage, or reduced cardiac output. These may produce mucosal injury,

hemorrhage, or even perforation. Chronic ischemia may result in intestinal stricture. Some cases of radiation enterocolitis exhibit reduced

mucosal blood flow.

Neoplastic Degeneration All GI regions are susceptible to malignant degeneration. In the United States, colorectal cancer is most common and usually presents after age 45 years. Worldwide, gastric cancer

is prevalent, especially in certain Asian populations. Esophageal cancer

develops with chronic acid reflux or after extensive alcohol or tobacco

use. Small-intestinal neoplasms are rare but occur with underlying

inflammatory diseases. Anal cancers arise after prior anal infection or

inflammation. Pancreatic and biliary cancers elicit severe pain, weight

loss, and jaundice and have poor prognoses. Hepatocellular carcinoma

usually arises in the setting of chronic viral hepatitis or cirrhosis

secondary to other causes. Most GI cancers exhibit carcinomatous

histology; however, lymphomas and other cell types also are observed.

Disorders without Obvious Organic Abnormalities The

most prevalent GI disorders show no abnormalities on biochemical or

structural testing and include IBS, functional dyspepsia, and functional

heartburn. These disorders exhibit altered gut motor function, but the

pathogenic relevance of these abnormalities is uncertain. Exaggerated

visceral sensory responses to noxious stimulation may cause discomfort in these disorders. Symptoms in other patients result from altered

processing of visceral pain sensations in the central nervous system.

Functional bowel patients with severe symptoms may exhibit significant emotional disturbances on psychometric testing. Subtle immunologic defects may contribute to functional symptoms as well.

Genetic Influences Although many GI diseases result from environmental factors, others exhibit hereditary components. Family

members of IBD patients show a genetic predisposition to disease

development themselves. Colonic, esophageal, and pancreatic malignancies arise in certain inherited disorders. Rare genetic dysmotility

syndromes are described. Familial clustering is observed in the functional bowel disorders, although this may be secondary learned familial

illness behavior rather than a true hereditary factor.

■ SYMPTOMS OF GI DISEASE

Symptoms of GI disease include abdominal pain, heartburn, nausea

and vomiting, altered bowel habits, GI bleeding, jaundice, and other

manifestations (Table 321-1).

Abdominal Pain Abdominal pain results from GI disease and

extraintestinal conditions involving the genitourinary tract, abdominal

wall, thorax, or spine. Visceral pain generally is midline in location

and vague in character, whereas parietal pain is localized and precisely

described. Painful inflammatory diseases include peptic ulcer, appendicitis, diverticulitis, IBD, pancreatitis, cholecystitis, and infectious

enterocolitis. Noninflammatory visceral sources include biliary colic,

TABLE 321-1 Common Causes of Common Gastrointestinal (GI) Symptoms

ABDOMINAL PAIN NAUSEA AND VOMITING DIARRHEA GI BLEEDING OBSTRUCTIVE JAUNDICE

Appendicitis Medications Infection Ulcer disease Bile duct stones

Gallstone disease GI obstruction Poorly absorbed sugars Esophagitis Cholangiocarcinoma

Pancreatitis Motor disorders Inflammatory bowel disease Varices Cholangitis

Diverticulitis Functional bowel disorder Microscopic colitis Vascular lesions Sclerosing cholangitis

Ulcer disease Cyclic vomiting syndrome Functional bowel disorder Neoplasm Ampullary stenosis

Esophagitis Cannabinoid hyperemesis syndrome Celiac disease Diverticula Ampullary carcinoma

GI obstruction Enteric infection Pancreatic insufficiency Hemorrhoids Pancreatitis

Inflammatory bowel disease Pregnancy Hyperthyroidism Fissures Pancreatic tumor

Functional bowel disorder Endocrine disease Ischemia Inflammatory bowel disease

Vascular disease Motion sickness Endocrine tumor Infectious colitis

Gynecologic causes Central nervous system disease

Renal stone

2383Approach to the Patient with Gastrointestinal Disease CHAPTER 321

mesenteric ischemia, and neoplasia. The most common causes of

abdominal pain are IBS and functional dyspepsia.

Heartburn Heartburn, a burning substernal sensation, is reported

intermittently by 40% of the population. Classically, heartburn results

from excess gastroesophageal acid reflux, but some cases exhibit normal esophageal acid exposure and are caused by reflux of nonacidic

material or heightened sensitivity of esophageal nerves.

Nausea and Vomiting Nausea and vomiting are caused by GI

diseases, medications, toxins, infection, endocrine disorders, labyrinthine conditions, and central nervous system disease. Mechanical

obstructions of the upper gut are commonly excluded as causes of

chronic nausea and vomiting, but disorders of propulsion including

gastroparesis and intestinal pseudoobstruction elicit similar symptoms.

Nausea and vomiting also are commonly reported by patients with IBS

and functional disorders of the upper gut (including chronic nausea

vomiting syndrome, cyclic vomiting syndrome, and cannabinoid

hyperemesis syndrome).

Altered Bowel Habits Altered bowel habits are common complaints in GI disease. Constipation may be reported as infrequent

defecation, straining with defecation, passage of hard stools, or a sense

of incomplete fecal evacuation and is caused by obstruction, motor

disorders, medications, and endocrine diseases such as hypothyroidism and hyperparathyroidism. Diarrhea may be reported as frequent

defecation, passage of loose or watery stools, fecal urgency, or a similar

sense of incomplete evacuation. The differential diagnosis of diarrhea

includes infections, inflammatory causes, malabsorption, and medications. IBS produces constipation, diarrhea, or an alternating bowel

pattern. Fecal mucus is common in IBS, whereas pus and blood characterize IBD. Steatorrhea develops with malabsorption.

GI Bleeding Hemorrhage may develop from any gut organ. Upper

GI bleeding presents with melena or hematemesis, whereas lower GI

bleeding produces passage of bright red or maroon stools. However,

briskly bleeding upper sites can elicit voluminous red rectal bleeding,

whereas slowly bleeding ascending colon sites may produce melena.

Chronic occult GI bleeding may present with iron deficiency anemia.

Causes of upper GI bleeding include ulcer disease, gastroduodenitis,

esophagitis, portal hypertensive etiologies, malignancy, tears across the

gastroesophageal junction, and vascular lesions. Lower GI sources of

hemorrhage include hemorrhoids, anal fissures, diverticula, ischemic

colitis, neoplasm, IBD, infectious colitis, drug-induced colitis, arteriovenous malformations, and other vascular lesions.

Jaundice Jaundice results from prehepatic, intrahepatic, or posthepatic disease. Posthepatic causes of jaundice include biliary diseases,

such as choledocholithiasis, acute cholangitis, primary sclerosing

cholangitis, other strictures, and neoplasm, and pancreatic disorders,

such as acute and chronic pancreatitis, stricture, and malignancy.

Other Symptoms Other symptoms are manifestations of GI disease. Dysphagia, odynophagia, and unexplained chest pain suggest

esophageal disease. A globus sensation is reported with esophagopharyngeal conditions, but also occurs with functional GI disorders.

Weight loss, anorexia, and fatigue present with neoplastic, inflammatory, motility, pancreatic, and psychiatric conditions. IBD is associated

with hepatobiliary dysfunction, skin and eye lesions, and arthritis.

Celiac disease may present with dermatitis herpetiformis. Jaundice can

produce pruritus. Conversely, systemic diseases have GI consequences.

Systemic lupus may cause gut ischemia, presenting with pain or bleeding. Severe burns may lead to gastric ulcer formation.

EVALUATION OF THE PATIENT

WITH GI DISEASE

Evaluation of the patient with suspected GI disease begins with a careful history and examination. Subsequent investigation with tools to

test gut structure or function and luminal constituents is indicated in

selected cases. In patients with normal findings on diagnostic testing,

validated symptom profiles are used to confidently diagnose a functional bowel disorder.

■ HISTORY

The history in suspected GI disease has several components.

Symptom timing, patterns, and duration suggest specific etiologies.

Short-duration symptoms commonly result from acute infection or

inflammation, toxin exposure, or ischemia. Long-standing symptoms

point to chronic inflammation, neoplasia, or functional bowel disorders. Luminal obstruction can present with dysphagia, nausea and

vomiting, bloating and distention, or constipation depending on the

site of blockage. Symptoms from mechanical obstruction, ischemia,

IBD, and functional bowel disorders are worsened by meals, while

ulcer symptoms may be relieved by eating or antacids. Ulcer pain

occurs intermittently over weeks to months, whereas biliary colic has

a sudden onset and lasts up to several hours. Acute pancreatitis pain is

severe and persists for days to weeks. Meals elicit diarrhea while defecation relieves discomfort in some cases of IBD and IBS. Functional

bowel disorders are exacerbated by stress. Sudden awakening from

sound sleep by pain suggests organic rather than functional disease.

Diarrhea from malabsorption usually improves with fasting, whereas

secretory diarrhea persists without oral intake.

Symptom relation to other factors narrows the list of diagnostic

possibilities. Obstructive symptoms with prior abdominal surgery

raise concern for adhesions. Loose stools after gastrectomy or cholecystectomy suggest dumping syndrome or postcholecystectomy diarrhea. Symptom onset after travel prompts consideration of infection.

Medications produce pain, altered bowel habits, or GI bleeding. Celiac

disease is prevalent in people of northern European descent, whereas

IBD is more common in Jewish populations. A sexual history may raise

concern for infection or immunodeficiency.

Working groups have devised symptom criteria to improve diagnosis of functional bowel disorders to minimize the numbers of unnecessary diagnostic tests performed. The best accepted symptom-based

criteria are the Rome criteria, which exhibit sensitivities and specificities of only 55–75% when tested against structural findings in IBS

and functional dyspepsia, indicating a need for careful test selection in

patients at high risk of organic disease.

■ PHYSICAL EXAMINATION

The physical examination complements information from the history.

Abnormal vital signs provide diagnostic clues and determine the need

for acute intervention. Fever suggests inflammation or neoplasm.

Orthostasis is produced by significant blood loss, dehydration, sepsis,

or autonomic neuropathy. Skin, eye, or joint findings may point to

specific diagnoses. Neck examination with swallowing assessment

evaluates dysphagia. Lung and cardiac examinations evaluate for

cardiopulmonary disease as causes of abdominal pain or nausea.

Pelvic examination tests for a gynecologic source of abdominal pain.

Rectal examination may detect blood, indicating mucosal injury or

neoplasm or a palpable inflammatory mass in appendicitis. Metabolic conditions and gut motor disorders have associated peripheral

neuropathy.

Abdominal inspection may reveal distention from obstruction,

tumor, or ascites or vascular abnormalities with liver disease. Ecchymoses develop with severe pancreatitis. Auscultation detects bruits or

friction rubs from vascular disease or hepatic tumors. Loss of bowel

sounds signifies ileus, whereas high-pitched, hyperactive sounds

characterize intestinal obstruction. Percussion assesses liver size and

detects shifting dullness from ascites. Palpation assesses for hepatosplenomegaly and neoplastic or inflammatory masses. Intestinal ischemia

elicits severe pain but little tenderness. Patients with visceral pain may

exhibit generalized discomfort, whereas those with parietal pain or

peritonitis have localized pain with involuntary guarding, rigidity, or

rebound. Patients with musculoskeletal abdominal wall pain may note

tenderness exacerbated by Valsalva or leg lift maneuvers.

■ TOOLS FOR PATIENT EVALUATION

Laboratory, radiographic, and functional tests assist in diagnosis of suspected GI disease. The GI tract also is amenable to internal evaluation

using endoscopy and to examination of luminal contents. Histopathologic examinations of GI tissues complement these tests.

2384 PART 10 Disorders of the Gastrointestinal System

Laboratory Laboratory tests facilitate diagnosis of GI disease.

Iron-deficiency anemia suggests mucosal blood loss, whereas vitamin B12

deficiency results from intestinal, gastric, or pancreatic disease. Either

can result from inadequate oral intake. Leukocytosis and increased

sedimentation rates and C-reactive proteins are found in inflammation, whereas leukopenia is seen in viremic illness. Severe vomiting or

diarrhea elicits electrolyte disturbances, acid-base abnormalities, and

elevated blood urea nitrogen. Pancreaticobiliary or liver disease produces elevated pancreatic or liver chemistries. Thyroid chemistries and

cortisol and calcium levels evaluate for endocrinologic causes of symptoms. Pregnancy testing is considered for women with unexplained

nausea. Serologic tests screen for celiac disease, IBD, connective tissue

diseases, and paraneoplastic dysmotility syndromes. Hormone levels

are obtained for suspected endocrine neoplasia. Intraabdominal malignancies produce tumor markers including the carcinoembryonic antigen CA 19-9 and α-fetoprotein. Blood testing also monitors medication

therapy, as with thiopurine metabolite levels in IBD. Pharmacogenetic

methods are being adopted to determine optimal patient populations

for GI medication use. In conditions including IBD, research into

novel biomarkers is being conducted to predict longitudinal course

and treatment response. Other body fluids are sampled under certain

circumstances. Ascitic fluid is analyzed for infection, malignancy, or

findings of portal hypertension. Urine samples screen for carcinoid,

porphyria, and heavy metal intoxication.

Luminal Contents Luminal contents can provide diagnostic clues.

Stool samples are cultured for bacterial pathogens, examined for leukocytes and parasites, or tested for Giardia antigen. Duodenal aspirates

can be examined for parasites or cultured for bacterial overgrowth.

Fecal fat is quantified in possible malabsorption. Fecal elastase can

be decreased with exocrine pancreatic insufficiency. Elevated fecal

calprotectin or lactoferrin is found in inflammatory conditions such

as IBD. Stool electrolytes can be measured in diarrheal conditions.

Laxative screens are performed for suspected laxative abuse. Fecal

immunochemical and DNA tests have assumed roles in colon cancer

screening in low-risk populations. Gastric acid is quantified to exclude

gastrinoma. Esophageal pH/impedance testing is done for refractory

symptoms of gastroesophageal reflux.

Endoscopy The gut is accessible to endoscopy, which can diagnose

causes of bleeding, pain, nausea and vomiting, weight loss, altered

bowel function, and fever. Table 321-2 lists common indications for

endoscopic procedures. Upper endoscopy evaluates the esophagus,

stomach, and duodenum, whereas colonoscopy assesses the colon

and distal ileum. Upper endoscopy is advocated as the initial test for

suspected ulcer disease, esophagitis, neoplasm, malabsorption, and

Barrett’s metaplasia because of its abilities to visualize and biopsy any

abnormality. Colonoscopy is the preferred procedure for colon cancer

screening and surveillance and to biopsy colitis or ileitis secondary

to IBD, infection, ischemia, and radiation. Sigmoidoscopy examines

the colon to the splenic flexure and excludes distal causes of bleeding, inflammation, or obstruction in young patients not at significant

risk for colon cancer. For elusive GI bleeding from arteriovenous

malformations or superficial ulcers, small-intestinal examination is

performed with push enteroscopy, capsule endoscopy, or doubleballoon enteroscopy. Capsule endoscopy also visualizes smallintestinal Crohn’s disease in individuals with negative radiography.

Endoscopic ultrasound (EUS) diagnoses and stages GI malignancy,

excludes choledocholithiasis, evaluates pancreatitis, and assesses anal

continuity. Endoscopic retrograde cholangiopancreatography (ERCP)

provides diagnoses of pancreatic and biliary disease.

The development of novel imaging protocols permits optical biopsies to define mucosal histology and detect dysplasia in

selected settings. Methods employed include narrow-band imaging,

TABLE 321-2 Common Indications for Endoscopy

UPPER ENDOSCOPY COLONOSCOPY

ENDOSCOPIC RETROGRADE

CHOLANGIOPANCREATOGRAPHY

ENDOSCOPIC

ULTRASOUND

CAPSULE

ENDOSCOPY

DOUBLE-BALLOON

ENDOSCOPY

Dyspepsia despite

treatment

Dyspepsia with signs of

organic disease

Refractory vomiting

Dysphagia

Upper GI bleeding

Anemia

Weight loss

Malabsorption

Biopsy radiologic

abnormality

Polypectomy

Place gastrostomy

Barrett’s surveillance

Palliate neoplasm

Sample duodenal tissue/

fluid

Remove foreign body

Endoscopic mucosal

resection or endoscopic

submucosal dissection

for dysplasia or early

cancer

Place stent across

stenosis

Endoscopic myotomy

for achalasia or

gastroparesis

Endoscopic bariatric

procedures

Cancer screening

Lower gastrointestinal

(GI) bleeding

Anemia

Diarrhea

Polypectomy

Obstruction

Biopsy radiologic

abnormality

Cancer surveillance:

family history prior polyp/

cancer, colitis

Palliate neoplasm

Remove foreign body

Place stent across

stenosis

Jaundice

Postbiliary surgery complaints

Cholangitis

Gallstone pancreatitis

Pancreatic/biliary/ampullary tumor

Unexplained pancreatitis

Pancreatitis with unrelenting pain

Fistulas

Biopsy radiologic abnormality

Pancreaticobiliary drainage

Sample bile

Sphincter of Oddi manometry

Staging of malignancy

Characterize and biopsy

submucosal mass

Bile duct stones

Chronic pancreatitis

Drain pseudocyst

Anal continuity

Direct stent placement

Obscure

bleeding

Suspected

Crohn’s disease

of the small

intestine

Ablation of smallintestinal bleeding

sources

Biopsy of suspicious

small-intestinal

masses/ulcers

2385Approach to the Patient with Gastrointestinal Disease CHAPTER 321

chromoendoscopy, confocal laser endomicroscopy, and optical coherence tomography in colitis, Barrett’s esophagus, and gastric cancer

surveillance. Artificial intelligence using machine learning techniques

shows promise in detecting dysplasia and early cancer in still images

from biopsy tissues.

Radiography/Nuclear Medicine Radiographic tests evaluate

gut diseases and extraluminal structures. Contrast radiography with

barium provides mucosal definition and can assess gut transit and

pelvic floor dysfunction. An esophagram is the initial procedure to

exclude subtle rings, strictures, or achalasia as causes of dysphagia,

whereas small-bowel contrast radiology detects intestinal tumors,

strictures, and fistulae and can estimate intestinal transit. Contrast

enemas are performed when colonoscopy is unsuccessful or contraindicated. Ultrasound and computed tomography (CT) evaluate regions

not accessible by endoscopy or contrast studies, including the liver,

pancreas, gallbladder, kidneys, and retroperitoneum, and are useful for

diagnosing mass lesions, fluid collections, organ enlargement, and, in

the case of ultrasound, gallstones. CT and magnetic resonance (MR)

colonography have been considered as alternatives to colonoscopy

for colon cancer screening but have not commonly been adopted.

MR methods image the pancreaticobiliary ducts to exclude neoplasm, stones, and sclerosing cholangitis and the liver to characterize

benign and malignant tumors. Specialized CT or MR enterography

quantifies IBD intensity. Angiography excludes mesenteric ischemia

and determines spread of malignancy. Angiographic techniques also

access the biliary tree in obstructive jaundice. CT and MR techniques

screen for mesenteric occlusion, thereby limiting exposure to angiographic dyes. Positron emission tomography (PET) can distinguish

malignant from benign disease in several organ systems. Imaging with

DOTA-octreotate and related agents has improved detection of neuroendocrine tumors by combined PET-CT techniques.

Scintigraphy evaluates structural abnormalities and quantifies luminal transit. Radionuclide scans localize bleeding sites in patients with

brisk hemorrhage to direct therapy with endoscopy, angiography,

or surgery. Radiolabeled leukocyte scans search for intraabdominal

abscesses not visualized on CT. Biliary scintigraphy complements

ultrasound in assessing for cholecystitis. Scintigraphy to quantify

esophageal and gastric emptying is well established, whereas techniques to measure small-intestinal or colonic transit are less widely

used.

Histopathology Endoscopic mucosal biopsies evaluate for inflammatory, infectious, and neoplastic disease. Deep rectal biopsies facilitate diagnosis of Hirschsprung’s disease or amyloid. Liver biopsy is

performed for abnormal liver chemistries, unexplained jaundice, and

some cases of viral hepatitis, and following liver transplant to exclude

rejection. Biopsies obtained during CT or ultrasound evaluate for

intraabdominal conditions not accessible by endoscopy.

Functional Testing Tests of gut function provide important data

when structural testing is nondiagnostic. Functional testing of motor

activity is provided by newer high-resolution manometric techniques.

Esophageal manometry is useful for suspected achalasia, whereas

small-intestinal manometry tests for pseudoobstruction and colon

manometry evaluates for colonic inertia. A wireless motility capsule

measures transit and contractile activity in the stomach, small intestine, and colon in a single test. Anorectal manometry with balloon

expulsion testing is used for unexplained incontinence or constipation

from outlet dysfunction. Biliary manometry tests for sphincter of Oddi

dysfunction with unexplained biliary pain. The endoluminal functional lumen imaging probe can measure reduced distensibility in the

lower esophageal sphincter in achalasia, the pylorus in gastroparesis,

and the anus for defecation disorders. Measurement of breath hydrogen while fasting and after oral mono- or oligosaccharide challenge

can screen for carbohydrate intolerance and small-intestinal bacterial

overgrowth. Urea breath testing assesses for persistent Helicobacter

pylori infection, while gastric emptying breath testing is an alternative

to scintigraphy for gastroparesis diagnosis.

TREATMENT

Gastrointestinal Disease

Management options for GI diseases depend on the cause of

symptoms. Available treatments include modifications of dietary

intake, medications, treatment of gut dysbiosis, luminal intubation,

interventional endoscopy or radiology techniques, surgery, psychological approaches, and physical therapy. Given the hereditary predisposition of many GI diseases, genetic testing may be indicated

in some patients. Improved smartphone applications are being

adopted for diverse purposes ranging from providing instructions

for endoscopy preparation to educating and promoting adherence

to diet restrictions in several disorders.

NUTRITIONAL MANIPULATION

Dietary modifications for GI disease include those that only

reduce symptoms, those that correct pathologic defects, or those

that replace normal food intake with enteral or parenteral formulations. Changes that improve symptoms but do not reverse

organic abnormalities include lactose restriction for lactase

deficiency, liquid meals in gastroparesis, carbohydrate restrictions with dumping syndrome, and low-FODMAP (fermentable

oligo-di-monosaccharides and polyols) diets in IBS. The glutenfree diet for celiac disease exemplifies a primary therapy to reduce

mucosal inflammation. Likewise, elimination diets may improve

histology and symptoms in some cases of eosinophilic esophagitis. Medium-chain triglycerides replace normal fats in short-gut

syndrome or severe ileal disease. Perfusing liquid meals through

a gastrostomy is performed in those who cannot swallow safely.

Enteral jejunostomy feedings are considered for gastric dysmotility syndromes that preclude feeding into the stomach. Intravenous

hyperalimentation is used for generalized gut malfunction, which

does not permit enteral nutrition.

PHARMACOTHERAPY

Several medications can treat GI diseases. Considerable resources

are expended on over-the-counter remedies. Many prescription

drug classes are offered as short-term or continuous therapy of GI

illness. Alternative treatments are popular in conditions for which

traditional therapies provide incomplete relief.

Over-the-Counter Agents Over-the-counter agents are reserved

for mild GI symptoms. Antacids, histamine H2

 antagonists, and

proton pump inhibitors (PPIs) decrease symptoms in gastroesophageal reflux disease (GERD) and dyspepsia. Fiber supplements, stool

softeners, enemas, and laxatives are used for constipation. Laxatives

are categorized as stimulants, osmotic agents (including isotonic

preparations containing polyethylene glycol), and poorly absorbed

sugars. Nonprescription antidiarrheal agents include bismuth subsalicylate, kaolin-pectin combinations, and loperamide, whereas

lactase enzyme pills are used for lactose intolerance. Gaseous symptoms may be reduced by bacterial α-galactosidase, antiflatulents,

and adsorbents. In general, using a nonprescription preparation for

more than a short time for chronic persistent symptoms should be

supervised by a health care provider.

Prescription Drugs Prescription drugs are approved for a broad

range of GI diseases. Higher-dose prescription PPIs are advocated

for GERD when over-the-counter preparations are inadequate.

Cytoprotective agents are available for upper gut ulcers but are less

frequently prescribed. Prokinetic drugs stimulate GI propulsion in

gastroparesis, pseudoobstruction, and slow-transit constipation.

Secretagogue drugs are prescribed for constipation refractory to

other agents, whereas peripheral opioid antagonists are offered for

opioid-induced constipation. Prescription antidiarrheals include

opioid drugs, anticholinergic antispasmodics, tricyclics, bile acid

binders, and serotonin antagonists. Antispasmodics and antidepressants also are useful for functional GI disorders, whereas

narcotics are used for pain control in organic conditions such as

disseminated malignancy and chronic pancreatitis. Antiemetics

2386 PART 10 Disorders of the Gastrointestinal System

reduce nausea and vomiting. Potent pancreatic enzymes decrease

malabsorption and pain from pancreatic disease. Antisecretory

drugs such as the somatostatin analogue octreotide treat hypersecretory states. Some functional GI disorders require use of neuromodulators, including tricyclic agents, for control of pain, diarrhea,

or nausea. Antibiotics treat H. pylori–induced ulcers, infectious

diarrhea, diverticulitis, intestinal bacterial overgrowth, and Crohn’s

disease. Anti-inflammatory and immunomodulatory drugs are used

in IBD, microscopic colitis, refractory celiac disease, autoimmune

pancreatitis, and gut vasculitis. Over the past decade, several newer

biologic agents, including agents that inhibit tumor necrosis activity, other proinflammatory cytokines, and Janus kinase signaling

or serve as antiadhesion molecules, have had dramatic impact in

Crohn’s disease and ulcerative colitis. Biologics that deplete eosinophils or inhibit mast cells show promise in eosinophilic disorders

of the gut. Chemotherapy with or without radiotherapy is offered

for GI malignancies. Most GI carcinomas respond poorly to such

therapy, whereas lymphomas may be cured with such intervention.

Complementary and Alternative Medicine Treatments Alternative treatments are marketed to treat GI symptoms. Ginger, acupressure, and acustimulation have been advocated for nausea, whereas

pyridoxine has been investigated for nausea of first-trimester pregnancy. Peppermint oil and carraway seed oil products and herbal

preparations such as STW 5 (a mixture of nine herbs) are useful

in cases of functional dyspepsia and IBS. Low-potency pancreatic

enzyme preparations are sold as general digestive aids but have little

evidence to support their efficacy.

THERAPIES TARGETING GUT DYSBIOSIS

Some cases of diarrhea-predominant IBS respond to nonabsorbable antibiotics. Oral antibiotics also are the mainstay of managing

intestinal bacterial overgrowth. Probiotics containing active bacterial cultures and prebiotics that selectively nourish nonnoxious

commensal bacteria are used as adjuncts in some cases of infectious

diarrhea and IBS, with limited evidence of efficacy. Transplantation

of donor feces into the colon by colonoscopy or enema is effective

treatment for recurrent, refractory Clostridium difficile colitis, and

numerous trials are being conducted to assess utility of this technique in IBS, IBD, and liver disease

LUMINAL SUCTION AND LAVAGE

Nasogastric tube suction decompresses the upper gut in ileus or

mechanical obstruction. Nasogastric lavage of saline or water in the

patient with upper GI hemorrhage determines the rate of bleeding

and helps evacuate blood before therapeutic endoscopy. Enteral

feedings can be delivered through nasogastric or nasoenteric tubes.

Enemas relieve fecal impaction or assist in gas evacuation in acute

colonic pseudoobstruction. A rectal tube can be placed to vent the

distal colon in colonic pseudoobstruction and other colonic distention disorders.

INTERVENTIONAL ENDOSCOPY AND RADIOLOGY

In addition to its diagnostic role, endoscopy has numerous therapeutic capabilities. Cautery techniques and injection of vasoconstrictor substances can stop hemorrhage from ulcers and vascular

malformations. Endoscopic encirclement of varices and hemorrhoids with constricting bands stops hemorrhage from these sites,

whereas endoscopically placed clips can occlude arterial bleeding sites. Endoscopically delivered hemostatic powder sprays are

approved to stop brisk GI bleeding. Endoscopy can remove polyps

or debulk lumen-narrowing malignancies. Colonoscopy can withdraw excess gas in some cases of acute colonic pseudoobstruction.

Endoscopic mucosal resection, submucosal dissection, and radiofrequency techniques can ablate some cases of Barrett’s esophagus

with dysplasia or superficial cancer and early gastric malignancies.

Obstructions of the gut lumen and pancreaticobiliary tree are

relieved by endoscopic dilation or placing plastic or expandable

metal stents. Endoscopic sphincterotomy of the ampulla of Vater

relieves symptoms of choledocholithiasis. Cholangioscopy can help

with stone lithotripsy in the common bile duct, ablation of small

ductal tumors, and placement of gallbladder stents to facilitate

drainage in nonoperative candidates. Methods employing interventional EUS have been developed for pancreatic cyst gastrostomy

using lumen-apposing metal stents, pancreatic necrosectomy, and

placement of fiducial markers to direct pancreatic and rectal radiotherapy. EUS also has been used to facilitate endoscopic access to

the excluded distal stomach in patients who have undergone bariatric gastric bypass surgery using similar stents so that ERCP can

be done for pancreaticobiliary conditions. Likewise, EUS-directed

stent placement can manage postsurgical stenoses after pancreatic

resection. Endoscopy is sometimes used to insert gastric feeding

tubes. Peroral endoscopic myotomy is therapeutically performed

on the lower esophageal sphincter in achalasia and on the pylorus

in gastroparesis. Endoscopic treatments for acid reflux including radiofrequency therapy, transoral fundoplication, endoscopic

stapling, and antireflux mucosectomy have been developed, but

many offer unproved utility. Endoscopic bariatric methodologies,

including intragastric balloons, endoscopic sleeve gastroplasty, and

duodenal resurfacing and diversion, have been introduced.

Radiologic measures also are useful in GI disease. Angiographic

embolization or vasoconstriction decreases bleeding from gut sites

not amenable to endoscopic intervention. Dilatation or stenting

with fluoroscopic guidance relieves luminal strictures. Contrast

enemas can reduce volvulus and evacuate air in acute colonic pseudoobstruction. CT and ultrasound help drain abdominal fluid collections, in many cases obviating the need for surgery. Percutaneous

transhepatic cholangiography relieves biliary obstruction when

ERCP is contraindicated. Transjugular intrahepatic portosystemic

shunts are commonly performed by interventional radiologists for

variceal hemorrhage not amenable to endoscopic therapy. Lithotripsy can fragment gallstones in patients who are not candidates

for surgery. Radiologic approaches are often chosen over endoscopy

for gastroenterostomy placement. Finally, central venous catheters for parenteral nutrition may be placed using radiographic

techniques.

SURGERY

Surgery is performed to cure disease, control symptoms, maintain

nutrition, or palliate unresectable neoplasm. Surgery can cure medication-unresponsive ulcerative colitis, diverticulitis, cholecystitis,

appendicitis, and intraabdominal abscess, but can only reduce

symptoms and treat disease complications in Crohn’s disease. Surgery is mandated for ulcer complications such as bleeding, obstruction, or perforation and intestinal obstructions that persist after

conservative care. Gastroesophageal fundoplication is performed

for severe ulcerative esophagitis and drug-refractory symptomatic acid reflux. Achalasia responds to operations to reduce lower

esophageal sphincter tone. Operations for motor disorders include

implanted electrical stimulators for gastroparesis and electrical

devices and artificial sphincters for fecal incontinence. Surgery may

be needed to place a jejunostomy for long-term enteral feedings.

PSYCHOLOGICAL APPROACHES AND PHYSICAL THERAPY

Psychological therapies, including psychotherapy, cognitive behavioral therapy, and hypnosis, have shown efficacy in functional

bowel disorders. Patients with significant psychological dysfunction

and those with little response to treatments targeting the gut are

likely to benefit from this form of therapy. Biofeedback methods

administered by physical therapies are accepted for treating refractory fecal incontinence or constipation secondary to dyssynergia.

■ FURTHER READING

Aslanian HR et al: AGA Clinical Practice Update on pancreas cancer

screening in high-risk individuals: An expert review. Gastroenterology 159:358, 2020.

Bajaj JS et al: Major trends in gastroenterology and hepatology

between 2010 and 2019: An overview of advances from the past

2387 Gastrointestinal Endoscopy CHAPTER 322

decade selected by the editorial board of the American Journal of

Gastroenterology. Am J Gastroenterol 115:1007, 2020.

Gupta S et al: Recommendations for follow-up after colonoscopy and

polypectomy: A consensus update by the US Multi-Society Task

Force on Colorectal Cancer. Gastroenterology 158:1131, 2020.

Keefer L et al: Best practice update: Incorporating psychogastroenterology into management of digestive disorders. Gastroenterology

154:1249, 2018.

Lamb CA et al: British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.

Gut 68:s1, 2019.

Osadchiy V et al: The gut-brain axis and the microbiome: Mechanisms and clinical implications. Clin Gastroenterol Hepatol 17:322,

2019.

322 Gastrointestinal

Endoscopy

Louis Michel Wong Kee Song, Mark Topazian

Gastrointestinal endoscopy has been attempted for >200 years, but

the introduction of semirigid and flexible gastroscopes in the

mid-twentieth century marked the dawn of the modern endoscopic

era. Since then, rapid advances in endoscopic technology have led to

dramatic changes in the diagnosis and treatment of many digestive

diseases. Innovative endoscopic devices and new endoscopic treatment

modalities continue to expand the use of endoscopy in patient care.

Flexible endoscopes provide an electronic video image generated

by a charge-coupled device (CCD) or a complementary metal oxide

semiconductor (CMOS) chip in the tip of the endoscope. Operator

controls permit deflection of the endoscope tip; fiberoptic bundles

or light-emitting diodes provide light at the tip of the endoscope;

and working channels allow washing, suctioning, and the passage of

instruments (Fig. 322-1). Progressive changes in the diameter and

stiffness of endoscopes have improved the ease and patient tolerance of

endoscopy. High-resolution and high-definition endoscopes equipped

with electronic and optical magnification capabilities enable acquisition of images with a high level of detail. Advanced imaging techniques, including narrow-band imaging (Fig. 322-2) and real-time

image-processing enhancement algorithms, aid in tissue characterization or differentiation.

ENDOSCOPIC PROCEDURES

■ UPPER ENDOSCOPY

Upper endoscopy, also referred to as esophagogastroduodenoscopy

(EGD), is performed by passing a flexible endoscope through the

mouth into the esophagus, stomach, and duodenum. The procedure is

the best method for examining the upper gastrointestinal mucosa

(Fig. 322-3). While the upper gastrointestinal radiographic series has

similar accuracy for diagnosis of duodenal ulcer (Fig. 322-4), EGD is

superior for detection of gastric ulcers (Fig. 322-5) and flat mucosal

lesions, such as Barrett’s esophagus (Fig. 322-6), and it permits

directed biopsy and endoscopic therapy. Intravenous sedation is given

to most patients in the United States to ease the anxiety and discomfort of the procedure, although in many countries, EGD is routinely

performed with topical pharyngeal anesthesia only. Patient tolerance of

unsedated EGD is improved by the use of an ultrathin, 5-mm diameter

endoscope that can be passed transorally or transnasally.

■ COLONOSCOPY

Colonoscopy is performed by passing a flexible colonoscope through

the anal canal into the rectum and colon. The cecum is reached in

FIGURE 322-1 Gastrointestinal endoscope. Shown here is a conventional

colonoscope with control knobs for tip deflection, push buttons for suction and

air insufflation (single arrows), and a working channel for passage of accessories

(double arrows).

A

B

FIGURE 322-2 Flat colon polyp. A. White-light imaging. B. Corresponding narrowband imaging enhances mucosal features and lesion delineation.