9A. Endoscopy - NASPGHAN

Section 9 - Diagnostic Tests 449

9A. Endoscopy

Roberto Gomez, MD Christine Waasdorp Hurtado, MD, MSCS, FAAP

I. Procedures Esophagogastroduodenoscopy (EGD) and colonoscopy allow for obtaining mucosal tissue to assist with

diagnosis. In addition, these procedures allow for access for therapeutic treatment of varices, GI bleeding, strictures, polyps and removal of foreign bodies.

II. EsophagogastroduodenoscopyA. Indications: vary with the age of the patient and include dysphagia, odynophagia, abdominal

pain, GI bleeding (hematemesis and hematochezia), intractable GERD, vomiting, anorexia, weight loss, failure to thrive, anemia of unclear etiology, diarrhea, and ingestions (foreign body and caustic). Therapeutic EGD indications include foreign body removal, stricture dilation, varices treatment and control of upper GI bleeding

III. ColonoscopyA. Indications: vary with age and include gastrointestinal bleeding, suspected inflammatory bowel

disease, cancer surveillance in both polyposis syndrome and IBD, anemia of unclear etiology, weight loss, failure to thrive and chronic diarrhea. Therapeutic colonoscopy indications include polypectomy, foreign body removal, decompression of toxic mega colon, dilatation of stricture and control of bleeding lesions

B. Contraindications of EGD and Colonoscopy1. Absolute contraindications include suspected perforation and peritonitis in a toxic

patient2. Relative contraindications include recent bowel surgery, coagulopathy, thrombocytope-

nia, neutropenia, connective tissues disorders such as Ehlers-Danlos with increased risk of perforation. Bowel obstruction and toxic dilation also hold an increased risk for perforation

3. IV. Preparation and Bowel Cleanout for Colonoscopy

A. Several regimens have been described to be effective for colonoscopy cleanout1. Polyethylene glycol and stimulant laxative 2. Magnesium citrate and stimulant laxative 3. Phosphate enema, bisacodyl and clear liquid diet

V. Complications of EGD and ColonoscopyA. Complications following EGD are rare, occurring in <2% of patients and include hypoxia sec-

ondary to sedation, bleeding, hematoma, perforation, missed lesions and infection. The risk of bleeding following EGD with biopsy is 0.3%. Perforation occurs in less than 0.3% of cases and infection is rarely reported

B. Complications of colonoscopy are equally infrequent, occurring in <2% of patients, and include hypoxia secondary to sedation, bleeding, hematoma, perforation, missed lesions and infection. Bleeding and perforation are the most likely complications occurring <0.3% and 0.3%, respectively

C. Identification of complications typically occurs in the first 24 hours after the procedure. Bleeding presents with hematemesis or bloody output from a gastrostomy tube in EGD patients and with hematochezia following colonoscopy. Repeat endoscopy is recommended for identification of the bleeding site and treatment with the appropriate therapy. Perforation is identified due to patient discomfort, fever, and tachycardia, with extraluminal air visualized on a radiograph. Conservative therapy with antibiotics and gut rest is the typical treatment

450 The NASPGHAN Fellows Concise Review of Pediatric Gastroenterology, Hepatology and Nutrition

VI. Findings of EGD and ColonoscopyA. Sufficient training and experience are required to allow for identification of normal and abnormal

gross findings. The EGD allows for visual identification of inflammation, ulcers, foreign bodies and hiatal hernia. Obtaining biopsies is vital to diagnosis. Similarly, colonoscopy can identify inflammation, ulcers, polyps and foreign bodies, but biopsies are paramount to diagnosis

Recommended Reading

Geboes K, Ectors N, D’Haens G, et al. Is ileoscopy with biopsy worthwhile in patients presenting with symp-toms of inflammatory bowel disease? Am J Gastroenterol. 1998;93(2):201-206.

Wyllie R, Kay MH. Gastrointestinal endoscopy in infants and children. Pediatr Rev. 1993;14(9):352-359.


9B. Intestinal Biopsy

Steve Min, MDCarolyn Sullivan, MD

I. Intestinal Biopsy in Infectious DiarrheaA. Bacterial

1. V cholera; minimal or no histologic change2. Shigella species: large bowel typically affected (mostly left-sided); hemorrhagic mucosa

with exudates that may form pseudomembranes, ulcers can be present; histologic features include cryptitis, crypt abscesses acutely, and may develop mucosal destruction with neutrophils and other inflammatory cells in lamina propria

3. E coli (EHEC): right side colon usually most severely affected, colonic edema, erosions, ulcers and hemorrhage; histologic findings include edema and hemorrhage in lamina propria/submucosa, mucosal acute inflammatory cells and necrosis; microthrombi may also be seen within small vessels

4. Salmonella (typhoid fever): may involve any level of GI tract (most prominent ileum, appendix, colon); thickened bowel wall, raised nodules (hyperplastic Peyer’s patches), ulcerations and necrosis; histological findings mostly involve hyperplasia of Peyer’s patches, with acute inflammation of the overlying epithelium

5. C difficile: classic pseudomembranous colitis findings include yellow-white pseudomembranes that are most commonly found in the left colon, with patchy distribution, often sparing the rectum; classic histologic findings involve the presence of volcano lesions (intercrypt necrosis and ballooned crypts give rise to the laminated pseudomembrane, and often with loss of superficial epithelial cells)

6. M tuberculosis: ileocecal and jejunoileal areas most commonly involved, followed by appendix and ascending colon; ICV may be deformed and gaping; strictures, ulcers, along with thickened mucosal folds, and inflammatory nodules; characteristic histologic finding is the caseating, often confluent granuloma which can be present at any level of the wall of the gut; acid-fast stains may demonstrate organisms within the granuloma

7. Yersinia: preferentially involves ileum, right colon, appendix; responsible for many cases of isolated granulomatous appendicitis

B. Viral1. Most enteric viruses that cause diarrhea (adenovirus, rotavirus, coronavirus, echovirus,

enterovirus, astrovirus, and Norwalk virus) are detected in stool samples and, rarely, by surgical pathology

2. CMV: may involve any part of the GI tract; most common gross lesion is ulceration, which may be single or multiple, and either superficial or deep; also may find mucosal hemorrhage, pseudomembranes and obstructive inflammatory masses; histologic findings vary, but may include minimal inflammation, deep ulcers with prominent granulation tissue; classic owl’s eye inclusions may be seen, usually in endothelial cells

3. Adenovirus may cause similar findings as CMV; however, the inclusions are usually crescent-shaped, and generally within the epithelium

C. Parasitic1. Many protozoal infections are also diagnosed by stool sample examination2. Giardia lamblia: endoscopic exam is generally unremarkable; biopsies may demonstrate

mild villous blunting, with increased lamina propria inflammatory cells; may find trophozoites (resembling pears cut lengthwise that contain 2 ovoid nuclei) at luminal surface

3. Entamoeba histolytica: coalescing small ulcers, which may form large, geographic ulcers; cecum most commonly involved, but can affect any level of colon or appendix; histo-logically, deep ulcers extending into submucosa found in advanced disease; organisms resemble macrophages with foamy cytoplasm – presence of ingested red blood cells are pathognomonic of E histolytica (hemophagocytosis)


II. Immunodeficiency-related Diarrheal DiseaseA. Common variable immunodeficiency (CVID)

1. Findings consistent with chronic infections can be found in CVID, most commonly from Giardia

2. Gastric mucosa with nonspecific increase in lamina propria lymphocytes3. Small bowel may include sprue-like lesions with villous blunting4. In contrast to celiac disease, the villous atrophy in CVID lacks crypt hyperplasia and

plasma cells are decreased in number5. Granulomatous enteropathy has been reported with CVID; poorly formed non-

necrotizing granulomas can be found in multiple sites throughout GI tract6. Nodular lymphoid hyperplasia found in up to 60% of patients with CVID7. Some may develop chronic inflammatory process involving small or large bowel, similar

to IBDB. Graft-vs-host disease (GVHD)

1. GI tract involvement occurs during acute GVHD2. Endoscopic findings include mucosal edema and erythema, as well as ulcers and

mucosal sloughing3. Histologic features are epithelial cell apoptosis and relatively sparse mononuclear

inflammatory cell infiltrate; apoptotic cells in the colon are also known as exploding crypt cells

4. In stomach, granular eosinophilic necrotic cellular debris may be present in the lumen of gastric glands; villous blunting can be seen in small bowel

III. Other Types of Diarrheal DiseaseA. Ulcerative colitis

1. Crypt distortion with villous surface, goblet cell depletion and prominent crypt abscesses2. Diffuse, predominantly plasma cell, infiltrate of lamina propria

B. Crohn disease1. Granulomas present in 25%–28% biopsies2. Crypts are generally well-aligned, despite moderate inflammatory infiltrate3. Crypt abscess and cryptitis are less constant than UC or infectious colitis4. Patchy inflammatory infiltrates

C. Celiac1. Loss of normal architecture with decrease in height of villi; crypt elongation or

hyperplasia; increased number of intraepithelial lymphocytes is characteristic; lamina propria also typically shows an increase in plasma cells

2. Important to note that all findings are nonspecific and may also be found in variety of other disease (i.e., tropical sprue, bacterial overgrowth, food allergies and CVID)

D. Cow’s milk protein allergy1. Mild-to-severe intraepithelial or lamina propria eosinophils, associated with epithelial

injury and edema; usually found in the colorectum, but may be found throughout the GI tract

E. Autoimmune enteropathy1. Variable flattening of villi with increase in number of lamina propria plasma cells; without

increase in intraepithelial lymphocytes2. Colon histology may range from normal to severe inflammation

F. Bacterial overgrowth syndrome1. May be histologically normal 2. May reveal mild-to-moderate villous blunting with chronic inflammation in lamina pro-

pria and epithelium3. Changes are patchy, and may vary from segment to segment

G. Microvillous inclusion disease1. Grossly, mucosa appears scalloped or atrophic; duodenal biopsies reveal

moderate-to-severe villous blunting, and no increase in either lamina propria inflammation or intraepithelial lymphocytes (unlike celiac)

2. Electron microscope findings are pathognomonic and reveal markedly decreased surface microvilli, which are shortened and disorganized in appearance

3. Intracytoplasmic vacuoles can be detected with PAS stain or with carcinoembryonic antigen immunostaining


H. Megaloblastic anemia – radiation and chemotherapy effect1. Variable villous abnormality with or without megaloblastic epithelial changes2. Focal necrosis of epithelial cells (apoptosis) and increased inflammatory cells within

mucosa/submucosa (similar to changes associated with folate/vitamin B12

deficiency) I. Whipple’s disease

1. Caused by Tropheryma whipplei, a rod-shaped micro-organism2. Diagnosis based on identification of PAS-positive, diastase-resistant bacilli within lamina

propria in small bowel biopsy specimensJ. Eosinophilic gastroenteritis

1. Scattered intramucosal eosinophils are normal in the GI tract (except the esophagus) 2. Diagnostic histology for EG in the appropriate clinical setting includes:

a. Collections of eosinophils not associated with other inflammatory cellsb. Groups of eosinophils associated with cryptitis or crypt abscessesc. Eosinophilic infiltration of the muscularis mucosae

K. Intestinal lymphangiectasia1. Histologic appearance in both primary and secondary forms involves dilated lymphatics

located in otherwise normal tissueL. Tufting enteropathy

1. Small bowel biopsies demonstrate variable villous abnormality, usually not associated with epithelial lymphocytosis, and a distinctive surface epithelial change consisting of epithelial crowding, disorganization and focal tufting

IV. Risk Associated With BiopsiesA. General

1. Complications associated with cold biopsy forceps in patients without coagulopathy are very rare

a. Risk of bleeding and perforation are both approximately 0.7%2. Complications from hot biopsy forceps or electrocautery snare resection include

hemorrhage, perforation and postcoagulation syndromea. Risk of significant hemorrhage from monopolar hot biopsy of a polyp is 0.39%b. Frequency of perforation from hot biopsy is 0.5%

3. Incidence of hemorrhage during colonoscopic polypectomy is 0.77%–2.24%, while perforation during colonoscopy occurs 0.11%–0.42%

4. In graft-vs-host disease, given the potential for desquamation, ulcerations and vesicobullous lesions, performing EGD and biopsy (particularly in duodenum) carries higher than normal risk of bleeding and perforation

B. Perforation1. Predisposing factors for perforation in the upper GI tract include presence of anterior

cervical osteophytes, Zenker’s diverticulum, esophageal strictures and malignancies2. Though uncommon, esophageal perforations are associated with a relatively high

mortality rate (approximately 25% in adult population) C. Bleeding

1. More likely in individuals with thrombocytopenia and/or coagulopathy2. In patients with platelet counts <20,000, biopsies should be performed with caution and

platelet transfusion should be considered prior to biopsy3. In general, standard biopsy techniques may be used in anticoagulated patients

D. Infection1. Transient bacteremia may occur during endoscopy, but is generally clinically insignificant

in pediatric patients2. Antibiotic prophylaxis for prevention of infective endocarditis (IE) is not indicated for any

endoscopic procedure, regardless of the cardiac condition, based on most recent ASGE/AHA guidelines

3. However, for patients with established GI tract infections in which enterococci may be part of the infecting flora, antibiotic prophylaxis may be considered for those with


cardiac conditions associated with the highest risk of adverse outcomes from IE. These include those with prosthetic valves, previous IE, cardiac transplant and subsequent valvulopathy, unrepaired cyanotic congenital heart disease and repaired CHD with prosthetic material

Recommended Reading

Standards of Practice Committee; ASGE. Antibiotic prophylaxis for GI endoscopy. Gastrointestinal Endoscopy. 2008;67:6.

Standards of Practice Committee; ASGE. Complications of upper GI endoscopy. Gastrointestinal Endoscopy. 2002;55:7.

Technology Assessment Committee; ASGE. Update on endoscopic tissue sampling devices. Gastrointestinal Endoscopy. 2006;63:6.

Walker WA, Kleinman RE, Sherman PM, Shneider BL, Sanderson IR. Pediatric Gastrointestinal Disease. 3rd ed. Hamilton, Ontario: BC Decker, Inc.; 2004: 1670-1671.

Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver Disease. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2006: 343.


9C. Liver Biopsy

Yonathan Fuchs, MD

I. Indications for Liver BiopsyA. Diagnosis

1. Alcoholic liver disease 2. Nonalcoholic steatohepatitis 3. Autoimmune hepatitis4. Hemochromatosis-index patient5. Wilson disease6. Cholestatic liver disease

a. Biliary atresia b. Primary sclerosing cholangitisc. Primary biliary cirrhosis (in adults)

7. Liver mass8. Liver rejection s/p transplant

B. Grading and staging1. Chronic hepatitis B and C (if treatment is a consideration)

C. Evaluation 1. Abnormal liver biochemical tests following inconclusive workup 2. Evaluation of fever of unknown origin, including tissue culture

II. Equipment and SonographyA. Suction-type devices (Jamshidi, Menghini)B. Spring-loaded cutting devices (Manopty)C. Suction needles generally produce larger specimens than spring-loaded needlesD. Ultrasonography prior to a liver biopsy defines the anatomy of the liver and the relative positions

of the gallbladder, lung and kidney

III. Risks:A. Minor complications: transient localized discomfort at the biopsy site and pain sufficient to

require analgesia. Referred pain to the right shoulderB. Major complications:

1. Perforationa. Pneumothorax and hemothoraxb. Bowel perforationc. Biliary perforation

2. Intraperitoneal hemorrhage 3. Bile peritonitis4. Infection5. Inadvertent renal puncture/biopsy

IV. Histologic FeaturesA. Neonatal Cholestasis

1. Critical role in the diagnosis of extrahepatic biliary atresia 2. Biopsy in biliary atresia will reveal

a. Bile ductular proliferation, canalicular and cellular bile stasis, and portal and perilobular edema and fibrosis

b. Bile plugs in bile ducts are relatively specific but are found in only 40% of biopsy specimens

3. Biopsy in neonatal hepatitis will reveala. Little or no bile duct alteration. Liver parenchyma abnormalities include giant cell

ballooning/degeneration, neutrophil infiltration, intralobular inflammation and Kupffer cell hyperplasia


B. Acute Hepatitis1. Inflammation is predominantly within the lobule. Hepatocellular injury is more

pronounced (edema and necrosis of individual hepatocytes, macrophages are enlarged and numerous)

C. Chronic Hepatitis1. Inflammation is within the portal tracts. Variable degree of parenchymal loss, scarring,

parenchymal regeneration and cirrhosis D. Acute Liver Failure

1. Massive confluent or multilobular necrosisE. Autoimmune Hepatitis

1. Dense mononuclear and plasma cell infiltration of the portal areas, which expands into the liver lobule; destruction of the hepatocytes at the periphery of the lobule, with erosion of the limiting plate (interface hepatitis) and hepatic regeneration with rosette formation

F. Drug-induced Hepatitis1. Prominence of neutrophils and eosinophils among inflammatory cells. Hepatocellular

injury can be spotty, affecting single hepatocytes, or it can be confluent, affecting groups of hepatocytes. Confluent necrosis can be zonal or non-zonal, depending upon the offending agent

2. Zonal necrosis is characteristic of compounds with predictable, dose-dependent, intrinsic toxicity, such as halothane (zone 3), carbon tetrachloride (zone 3), and acetaminophen (zone 3)

G. PSC1. Obliterative atrophy of septal or trabecular ducts proximal to sites of large duct scarring

(progressive ductal lesions)2. Focal concentric edema and fibrosis (onion skinning) around interlobular bile ducts

H. NASH1. Ballooning degeneration of hepatocytes, macrosteatosis and perisinusoidal fibrosis

I. Wilson Disease1. Early stages marked by steatosis of hepatocytes, mild chronic hepatitis, portal tract fibro-

sis and scant stainable copper2. Characteristic ultrastructural lesions seen via EM: hepatocellular mitochondria are pleo-

morphic and abnormally large, and show widened intracristal spaces, increased matrix density and large granules

J. Reye Syndrome1. Caused by the interaction of a viral infection and salicylate use or some underlying

undefined metabolic-genetic predisposition2. Liver biopsy demonstrates microvesicular steatosis in the absence of hepatic

inflammation or necrosis and characteristic swelling and pleomorphism of mitochondria under EM

K. α1-AT deficiency1. Periodic acid-Schiff-positive, diastase-resistant globules in the endoplasmic reticulum of

hepatocytes. Variable degrees of hepatocellular necrosis, inflammatory cell infiltration, periportal fibrosis or cirrhosis may be present

L. Portal Hypertension1. Portal vein thrombosis

a. Portal venules are small in caliberb. Parenchymal atrophy, especially in centrilobular regions

2. Congenital hepatic fibrosisa. Portal tracts are expanded by fibrosis and contain increased numbers of dilated

bile ducts at the limiting plate


V. Post-Transplant RejectionA. Histologic changes are variableB. The classic triad for acute cellular allograft rejection is: mixed portal tract inflammation, portal

venule endothelialitis and inflammatory-mediated bile duct damageC. May present with necrosis in the pericentral vein (zone 3) and lymphocytic infiltration in the

central vein as central venulitis, or lymphocytic infiltration in the portal zone either in bile ducts or portal vein as portal venulitis

D. Involvement of vascular system is usually suggestive of more severe rejection

Recommended Reading

Suchy FJ, Sokol RJ, Balistreri WF. Liver Disease in Children. 3rd ed. New York, NY: Cambridge University Press; 2007.

Van Thiel DH, Gavaler JS, Wright H, Tzakis A. Liver biopsy. Its safety and complications as seen at a liver transplant center. Transplantation. 1993;55:1087.

Walker WA, Kleinman RE, Sherman PM, Shneider BL, Sanderson IR. Pediatric Gastrointestinal Disease. 4th ed. Hamilton, Ontario: BC Decker, Inc.; 2006.

Wyllie R, Hyams S, Kay M. Pediatric Gastrointestinal and Liver Disease. 4th ed. Philadelphia, PA: Elsevier Saunders; 2011: 859-860.


9D-1. Additional Studies—Esophageal pH and

Impedance Monitoring

Lillienne Yoon, MDRina Sanghavi, MD

I. Esophageal pH MonitoringA. Esophageal pH monitoring is a way to study acid reflux (pH <4) in patients and correlate with

symptoms (an event marker)1. Can quantify the amount of reflux:

a. # of episodes with a drop in pH <4.0b. # of episodes of certain duration of pH <4.0c. Duration of intraesophageal pH <4.0.

B. Traditionally, it is the standard test for diagnosing GERDC. Esophageal pH can be monitored by a transnasal catheter or wireless pH capsule (Bravo)

1. Transnasal flexible catheter is positioned with the distal pH sensor 5 cm above the LES in adults and 13% of the esophageal length in children. Reproduceability of results depends on comparable placement of the pH sensor

a. How to verify position of catheter1) Esophageal manometry: optimum method but not ideal for pediatrics

(time consuming and invasive)2) Fluoroscopy, calculating esophageal length according to Strobel’s formula

(distance from the nose to the cardia) and endoscopy have been used instead in pediatrics

b. The two most common pH electrodes are glass and antimony1) Glass is considered the best sensor but it is expensive, large in diameter2) Antimony has smaller diameter (more comfortable) can hold multiple

pH sensors3) pH sensors need a reference electrode, which can be external or internal

a) External electrodes—less reliable due to problems with high body temperature or sweat, which can lead to inaccurate pH values

b) Internal reference is more difficult to make but it is more reliable4) The data from glass sensors vs antimony sensors do not correlate, so one

cannot reference normal ranges with each other5) In-vitro 2-point calibration of the pH sensors is performed prior to the

study and when the test is completec. Dual channel (proximal and distal esophagus) can be used to evaluate patients

with GERD off therapy, or dual channel (distal esophagus and gastric) can be used to evaluate patients with GERD on therapy (Figure 1B)

2. Bravo pH capsule has antimony electrode, internal reference, and is placed by endoscopy at 6cm above the Z line in adults

a. Advantages: more comfortable, can record 48–72 hours, no risk of slipping into the stomach

b. Disadvantages: expensive, invasive (need endoscopy), single location3. Interpreting pH monitoring

a. Can use scoring system like Johnson and DeMeester Score system, or refer to normal ranges created below


Table 1. Catheter-based Dual-probe (distal and proximal) Esophageal pH Monitoring

Variable Normal

Proximal (%) Distal (%)

Time pH <4.0 (%)

Total period < 0.9 < 4.2

Upright period < 1.2 < 6.3

Recumbent period < 0.0 < 1.2

Distal = 5 cm above manometric – defined proximal border of the LES.

Proximal = 20 cm above manometric – defined proximal border of the LES.

Catheter free distal esophageal pH monitoring17

Variable Normal

Distal (%)

Time pH <4.0 (%)

Total period < 5.3

Upright period < 6.9

Recumbent period < 6.7

Distal = 6 cm above endoscopic – defined gastroesophageal junction

Adapted from Tutuian R, Castell DO. Gastroesophageal reflux monitoring: pH and impedance. GI Motility Online. 2006.

4. Most relevant parameters are the acid exposure time or reflux index (the % of time of the entire duration of the investigation during which the pH is <4)

a. reflux index <3 is normalb. reflux index 3–7 is indeterminatec. reflux index >7% abnormal

II. ImpedanceA. Impedance can monitor the resistance to current flow (impedance) between two electrodes from

either liquid or gas bolus

FIGURE 2 . The esophagus starts at a resting value at baseline (A) that represents the collapsed esophageal walls on the catheter. When a swallow is initiated, air is also swallowed. Air enters in the first measuring segment causing an increase in impedance (B). After the passage of air, the bolus causes a decrease in impedance due to its conductivity and its effect on luminal dilatation (C). The bolus enters, traverses, and exits the measuring segments (C, D, and E, respectively). After the passage of the bolus, the lumen-occluding contraction (F) causes an increase in impedance. If the contraction wave completely clears the bolus from the segment, then a return to the original impedance baseline is seen (G).

Adapted from Di Pace M, Caruso A, Catalano P, Casuccio A, De Grazia E. Evaluation of esophageal motility using mulitchannel intraluminal impedance in healthy children and children with gastroesophageal reflux. J Ped Gastroenterol Nutrition. 2011;52:26-30.


B. There is a combined MII-pH catheter for esophageal monitoring for GERD1. It has become the preferred method of testing patients with persistent symptoms on

acid suppressive therapy, as it can clarify whether symptoms are associated with acid or nonacid reflux or not associated with reflux

2. A recent consensus report provided a detailed nomenclature for the reflux patterns detected by impedance-pH monitoring

a. Reflux is defined as either pure liquid or a mixture of liquid and gas detected by impedance

b. Liquid-only reflux is defined as a retrograde 50% decrease in impedance from the baseline in the 2 distal impedance sites

c. Gas reflux is defined as a simultaneous increase in impedance >3,000 Ω in any 2 consecutive impedance sites with 1 site having an absolute value >7,000 Ω

d. Mixed liquid gas reflux is defined as gas reflux occurring during or immediately before liquid reflux

3. Transnasal catheter design:a. It has 1 pH sensor that is placed above the LESb. It has impedance sensors 3, 5, 7, 9, 15, 17 cm above the LES

4. Principles of the MII-pH catheter:a. Reflux frequencyb. Esophageal height and duration of reflux episodesc. Detect nonacid refluxd. Detect gas vs liquid reflux

5. There are no normal ranges in impedance but there are some guidelines: (see Table 2)6. In general, impedance will detect more reflux episodes, since it can detect nonacid

reflux compared to pH probe alone

Table 2. Liquid GER and Gas RefluxLiquid GER - Drop in impedance to less than 50% of baseline

values

Gas Reflux - Rapid and pronounced rise in impedance (low

electrical conductivity)

Acid GER1. pH falls <4 for at least 4 secs or2. pH already <4, decreases by at least 1 pH unit for

more than 4 secsNonacid GER-Weakly acidic and alkaline GER

Weakly acidic reflux-pH drop of at least 1 pH unit sustained for more than 4 secs with basal pH remaining between 7 and 4

Alkaline-pH does not drop below 7Adapted from Vandenplas Y. Esophageal pH and Impedance Measurement. In Kleinman R, Sanderson I, Goulet O, Sherman P, Mieli-Vergani G, Shneider B, eds. Walker’s Pediatric Gastrointestinal Disease. Vol 2. Hamilton, Ontario: BC Decker Inc; 2008:1393-1400.

III. Preparation/Performing pH MonitoringA. Patient preparation rule of thumb:

1. Fasting for 3–5 hours prior to procedure2. Sedation should not be used because it can interfere with swallowing and influences LES

pressures3. Histamine and proton pump inhibitors should be stopped at 3 or 7 days, respectively

(the exception would be to see the acid-blocking effect of the drug)4. Antacids are fine up to 6 hours prior to the start of the recording5. Prokinetics should be stopped at least 48 hours prior to test6. For radiology studies, pH monitoring can be done at least 3 hours after barium or

nucleotide gastric/esophageal study


B. Duration: at least 18–24 hours spanning day and night1. GERD and esophageal acid exposure is highest during the day2. There is substantial evidence that there are more reflux episodes during the day than at

night (likely due to eating and physical activity)3. In general, it is noted that there are more acid reflux during fasting and more nonacid

reflux during feeding

IV. Recording Conditions Influenced by Patient-related FactorsA. Diet

1. Debate: during the test, the diet is restricted (nonacidic foods/drinks, etc). However, if the diet is restricted, then it is not the norm for the patient, so it may lead to non-realis-tic results.

2. Rule of thumb:a. Avoid hot or ice cold beverages and foods (electrodes are temperature sensitive)b. Avoid chewing gum and hard candy (increases saliva production, which increases

peristalsis and swallowing, which tends to normalize results)c. If drinking alcohol or smoking, it should be noted in diaryd. Fatty foods prolong postprandial gastric antiacidity and delay gastric emptying

3. With infants, it is suggested to replace one of the feedings with apple juice to solve the problem of gastric buffering after a milk feeding

B. Position1. There are data that prone sleeping is the preferred position for infants with GER (the

problem is SIDS)2. There is data suggesting that prone anti-Trendelenburg 30o sleeping position reduces

GER in normal subjects (difficult for infants)C. Physical activity can also precipitate reflux

Recommended Reading

Di Pace M, Caruso A, Catalano P, Casuccio A, De Grazia E. Evaluation of esophageal motility using mulitchannel intraluminal impedance in healthy children and children with gastroesophageal reflux. J Ped Gastroenterol Nutrition. 2011;52:26-30.

Hirano I, Richter J; Practice Parameters Committee of American College of Gastroenterology. ACG Practice Guidelines: Esophageal Reflux Testing. Am J Gastroenterol. 2007;102:668-685.

Vandenplas Y. Esophageal pH and Impedance Measurement. In Kleinman R, Sanderson I, Goulet O, Sherman P, Mieli-Vergani G, Shneider B, eds. Walker’s Pediatric Gastrointestinal Disease. Vol 2. Hamilton, Ontario: BC Decker Inc; 2008:1393-1400.


9D-2. Additional Studies—Gastric Function Tests

Leonel Rodriguez MD, MS

I. Evaluation Evaluation of gastric function focuses on ability to accommodate and empty, motility, electrical activity

and acid secretion.

II. Gastric Acid SecretionA. Quantitation of total gastric acid secretion at rest and after stimulationB. Most commonly used to evaluate conditions with abnormally low secretion (atrophic gastritis,

Menetrier disease, pernicious anemia) or high acid secretion (Zollinger-Ellison syndrome)C. Nasogastric tube used to aspirate gastric juice in 15-minute aliquotsD. Basal acid output (BAO)

1. 15 minute aspirate of fasting gastric juice is titrated with NaOH to neutrality2. Normal BAO in children is 0.03–0.05 mEq/kg/hour 3. Suspect Zollinger-Ellison syndrome if BAO is >15 mEq/hour

E. Pentagastrin stimulation performed when BAO is low or absent1. Pentagastrin (6 mcg/kg) given IV and 15 minute aspirations performed for 45–60

minutes to calculate the maximal acid output (MAO)F. Normal values for MAO are 18–28 mEq/h in men, 11–21 mEq/h in womenG. 0.031 mEq/kg/h at 1 month of ageH. 0.122 mEq/kg/h at 3 monthsI. 0.218 mEq/kg/h at 20 months with no significant change thereafter

III. Gastric Myoelectrical ActivityA. Electrogastrography (EGG)

1. Noninvasive external electrodes record gastric myoelectric activity2. Normal rhythm is 3 contractions per minute (cpm) corresponding to gastric pacemaker

generated gastric slow waves3. Does not correlate to gastric emptying by scintigraphy and ultrasonography4. May help differentiate children with normal and abnormal antroduodenal manometry 5. Limited application because of lack of standardization and significant motion artifacts6. EGG can be an adjunct in the evaluation of patients with functional and motility

gastrointestinal disorders

IV. Gastric Emptying StudiesA. Scintigraphy

1. Evaluates gastric emptying of a meal labeled with Tc99 sulfur colloid and/or Indium-1112. Simultaneous estimates of solid and liquid phase emptying using two labels 3. Area over the stomach scanned intermittently for up to 120 minutes after administration

of labeled meal, and amount of tracer remaining used to calculate % emptying4. Most studies estimate 50% emptying in 1 hour is normal, >60% emptying at 2 hours

and >90% emptying at 3 hours5. Important drawback—lack of pediatric standards, lack of standard test meal both type

and volume, radiationB. Breath test

1. Measures ratios of C12 and C13 in breath after a meal enriched in C13 and compares to known ratios in atmosphere

2. Amount of C13 enrichment in breath hydrogen on serial measurements is related to gastric emptying rate


3. C13 octanoic acid used to label solids. C13 sodium acetate used to label liquids4. Breath test has poor correlation with scintigraphy and poor relationship to dyspeptic

symptoms5. In children the ½ emptying of C13-sodium acetate correlates with gastric emptying

measured by scintigraphy in children with gastroparesis, and discriminates healthy volunteers from children with gastroparesis symptoms

6. Useful when radiation must be avoided (pregnancy) and in patients with aspiration risk and patient unable to be moved to radiology

7. Advantage: noninvasive, low cost8. Most important limitation is that test requires normal intestinal, hepatic, and pulmonary

functions, and reproducibility is poorC. Ultrasonography (US)

1. Most common technique—serial measurements of antral area (related to antral volume) after a meal to estimate the time to return to baseline area or 50% baseline area

2. Good correlation with scintigraphy for gastric emptying of liquids in healthy and diabetic adults

3. In children, correlates well with scintigraphy but limited by the overlapping of duodenum and shadowing of the gastric antrum by air

4. US particularly useful in patients on a liquid diet (preterm infants)5. Advantage: noninvasive 6. The test is limited by its poor reproducibility, lack of standard protocols, operator depen-

dency and interference by intestinal air

V. Gastric Receptive Accommodation TestsA. Gastric barostat

1. Gold standard for evaluating gastric accommodation to distension2. Utilizes an intragastric balloon manometer inflated to varying degrees3. Not available for clinical practice

B. Ultrasonography 1. An attractive, noninvasive alternative to the barostat2. Measures the gastric area or volume during and after a test meal to evaluate the

percentage of emptying over time and also gastric accommodation. No significant intra and interobserver variability, but moderate day-to-day variability in healthy adult volunteers

3. Reliable to evaluate accommodation in subjects with functional dyspepsia and in children with recurrent abdominal pain

Recommended Reading

Abell TL. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. Am J Gastroenterol. 2008;103(3):753-763.

Di Lorenzo C. Is electrogastrography a substitute for manometric studies in children with functional gastroin-testinal disorders? Dig Dis Sci. 1997;42(11):2310-2316.

Rao SS. Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies. Neurogastroenterol Motil. 2001;23(1):8-23.


9D-3. Additional Studies—Motility Testing

Meenakshi Rao, MD, PhDSamuel Nurko, MD

I. Anorectal Manometry (ARM)

II. Indications for ARMA. To diagnose a nonrelaxing internal anal sphincter—as found in Hirschsprung’s disease and IAS

achalasia (patients with normal rectal biopsy and abnormal sphincter)B. To diagnose pelvic floor dyssynergiaC. To evaluate patients with fecal incontinenceD. To decide if the patient is a candidate for biofeedback therapyE. To evaluate postoperative patients after imperforate anus repairF. To evaluate postoperative patients with Hirschsprung’s that have obstructive symptoms, and to

evaluate the effect of botulinum toxin

III. ARM Procedure A. Rectal distension with a balloon catheter to assess for the presence of the rectoanal inhibitory

reflex (RAIR), the reflexive relaxation of the internal anal sphincter (IAS) upon distention of the rectum (Figure 1). This relaxation is absent in patients with Hirschsprung’s disease (Figure 2)

1. Good screening test (sensitivity 91%, specificity 98%) 2. Higher probability of false negative result in neonates, especially preterm infants3. May require sedation in patients unable to cooperate

Figure 1. Normal IAS relaxation (RAIR) after balloon distention.

Figure 2. Non-relaxing internal anal sphincter (IAS).

Rodriguez L, Nurko, S Gastrointestinal motility procedures. In Wyllie et al editors: Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier, 2011; pp686-698.

IV. Antroduodenal (AD) ManometryA. Measures intraluminal pressures of antrum and duodenum, providing information on contraction

patterns of upper GI tract


V. Indications for AD ManometryA. Establish the presence or absence of chronic intestinal pseudo-obstruction (CIPO)B. Classify pattern of dysfunction in patients with CIPO (myopathic vs neuropathic) and provide

prognostic information (likelihood of successful enteral feeding)C. Exclude a motility problem as the basis of the patients’ symptoms (i.e., show normal findings in

children with apparent intestinal failure)D. Evaluation of unexplained nausea and vomitingE. Distinguish between rumination and vomitingF. Exclude generalized motility dysfunction in patients with dysmotility elsewhere. For example, as-

sess small bowel motility prior to colectomy for intractable constipationG. Assess motility in patients with CIPO being considered for intestinal transplantation. May suggest

unexpected obstruction

VI. AD Procedure A. A motility catheter is placed across the antrum and into the duodenum, either by endoscopy or

fluoroscopy B. Medications that affect motility should be discontinued at least 48 hours prior to testingC. Catheters should be tailored to patient size and information needed (minimum 1 antral and 3

small bowel recording sites; with a distance of 3 cm between ports)D. Distance for duodenal and jejunal ports varies depending on the age of the patient, with a range

from 3– 10 cm between ports. In most children, a distance of 3 cm is sufficientE. The position of the catheter needs to be checked frequently by fluoroscopy during the

performance of the test to ensure the correct position across the antroduodenal junction F. Compared to stationary tests, ambulatory tests cannot be used reliably to assess postprandial

antral activity due to frequent catheter displacement G. Antroduodenal contraction is then monitored for at least 3 hours in fasting state, and 1 hour

after ingestion of a standardized meal1. Type and size of meal should be adjusted according to patients’ age and preference (at

least 10 kcal/ kg or 400 kcal; >30% kcal from lipids)2. Meal should be administered by mouth or into the stomach if possible

H. If no motor migrating complex (MMC) seen in fasting state, then stimulated with erythromycin 1 mg/kg IV over 30 minutes

I. If no MMC observed despite erythromycin stimulation, then octreotide given SQ

VII. Interpreting Results of AD ManometryA. During fasting, the stomach and small bowel show a cyclic pattern, known as the motor

migrating complex (MMC) which has three phases: I, II and III 1. Phase I is the most characteristic and consists of regular rhythmic peristaltic contractions

that start proximally and migrate down to the ileum 2. Phase II shows regular contractions that occur in the antrum at a rate of 2–3/min and in

the small bowel at 11–12/min 3. Phase III is followed by a period of quiescence (Phase I) that is interrupted by irregular

motor activity (Phase II) (Figure 3)B. After the ingestion of nutrients, the fasting pattern is interrupted by what has been termed the

fed pattern1. Fed pattern is characterized by an irregular occurrence of contractions with various

amplitudes in the antrum and duodenum (Figure 4)C. Normal physiology: if Phase III MMC is present in fasting state or induced with erythromycin,

enteric neurons are likely intact


Figure 3. Normal fasting antroduodenal manometry. First 3 ports are in the antrum and lower 5 ports are in the duodenum. Ibid.

Figure 4. Normal fed antroduodenal manometry. First port is in the antrum, lower 7 ports are in the duodenum. Id.

Figure 5. Neuropathic pseudobstruction. Id. Figure 6. Myopathic pseudobstruction. Id.

VIII. Abnormal Motility PatternsA. CIPO

1. Neuropathic – antral hypomotility, absence of Phase III activity or abnormal propagation of Phase III MMC activity, bursts of uncoordinated activity (hypercontractility) and lack of fed response (Figure 5)

2. Myopathic – normal Phase III activity, but markedly low amplitude of contractions (<20 mm Hg) (Figure 6)

B. Postprandial antral hypomotility: seen in gastroparesis. Reduced motility index of postprandial distal antral contractions correlates with impaired gastric emptying of solids

C. Rumination: simultaneous contractions or R waves are associated with regurgitationD. Mechanical obstruction: postprandial clustered contractions lasting >30 minutes, separated by

quiescence or prolonged contractions


Recommended Reading

De Lorijn F, Reitsma JB, Voskuijl WP, et al. Diagnosis of Hirschsprung’s disease: a prospective, comparative accuracy study of common tests. J Pediatr. 2005;146(6):787-792.

De Lorijn F, Kremer LC, Reitsma JB, Benninga MA. Diagnostic tests in Hirschsprung disease: a systematic review. J Pediatr Gastroenterol Nutrition. 2006;42(5):496-505.

Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutrition. 2006;43(3):e1-13.

Meunier P, Marechal JM, Mollard P. Accuracy of the manometric diagnosis of Hirschsprung’s disease. J Pediatr Surg. 1978;13:411-415.

Nurko S. Gastrointestinal Manometry. Methodology and Indications. In: Kleinman RE, Goulet O-J,Mieli-Vergani, Sanderson IR, Sherman PM, eds. Walker’s Pediatric Gastrointestinal Disease. 5th ed. Lewiston, NY: BC Decker Inc.; 2008; 1375-1391.

Rodriguez L, Nurko S. Gastrointestinal motility procedures. Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver Disease. 4th ed. Philadelphia, PA: Saunders Elsevier; 2011: 686-698.


9D-4. Additional Studies—Pancreatic Function Tests

Gia Bradley, MDAnn Scheimann, MD, MBA

I. Indications for Pancreatic Function TestsA. Differentiate pancreatic malabsorption from other causes of malabsorptionB. Serial assessment of pancreatic exocrine function in diseases affecting the pancreasC. Assess efficacy of pancreatic enzyme replacement in children with malabsorption secondary to

exocrine pancreatic dysfunction

II. Direct tests—Exogenous hormonal stimulationA. Description

1. Secretin, cholecystokinin, or both administered intravenously to stimulate pancreatic secretion

a. The combination of secretin and cholecystokinin provides the most information about pancreatic exocrine function

2. The stomach and duodenum are intubateda. Gastric intubation required to remove gastric secretions that would interfere with

measurement of water and bicarbonate secretion from the pancreasb. Duodenal tube used for infusion of a nonabsorbable marker and for collection of

pancreatic secretions3. Measurements obtained on aspirated duodenal fluid

a. Bicarbonate concentrationb. Amylase, trypsin, chymotrypsin and lipase activitiesc. Concentration of the nonabsorbable marker

1) Enzyme activities and ion concentration are corrected for percent recovery of the nonabsorbable marker

B. Advantages1. Most accurate assessment of exocrine pancreatic function2. Test allows classification of mild, moderate or severe pancreatic exocrine dysfunction

C. Disadvantages1. Requires duodenal intubation and intravenous administration of hormones2. No standard method for secretin/CCK stimulation

III. Indirect tests of Pancreatic Exocrine FunctionA. Lundh test meal

1. Descriptiona. Subject ingests a 300-mL liquid test meal composed of dried milk, vegetable oil

and dextrose (6% fat, 5% protein and 15% carbohydrate)b. Duodenum is aspirated for a defined time after ingestionc. Fluid analyzed for enzyme activity (usually only trypsin is measured)

2. Advantagesa. More physiologic than exogenous hormone stimulationb. Does not require intravenous administration of hormonesc. Allows for detection of moderate or severe exocrine pancreatic dysfunction when

a direct test cannot be done


3. Disadvantagesa. Requires duodenal intubation, a test meal, and normal anatomy, including normal

small intestinal mucosa1) Test relies on endogenous hormones to stimulate pancreatic secretion, so

conditions like celiac disease can lead to poor physiological stimulation of the pancreas

b. Less sensitive than direct tests in detecting mild exocrine pancreatic dysfunction1) Only enzyme concentrations rather than enzyme output can be

determined because a marker is not used2) Increased potential for acid and pepsin to enter the duodenum, which can

prevent accurate measurements of enzyme concentrationsB. Measurement of fecal fat

1. Descriptiona. The patient consumes a diet adequate in fat intake for 3 daysb. Some experts recommend giving a nonabsorbed marker (charcoal, methylene

blue) at start and end of 72 hours c. All stool output collected for 72 hours (or all stools passed from appearance of

first marker to the appearance of the second marker in stool)d. Fat extracted from homogenized stool collection and weighed

2. Advantagesa. Quantitative measurement of steatorrhea

1) Steatorrhea does not occur until stimulated pancreatic lipase output is less than 5%–10% of normal

2) Normal fat excretion is 7% or less of ingested fat; infants may excrete up to 15% of dietary fat

3. Disadvantagesa. Requires sufficient dietary fat intake and accurate collection of stoolb. Only detects severe pancreatic dysfunction

C. Measurement of fecal chymotrypsin and elastase 11. Description

a. Chymotrypsin 1) Reliably differentiates between pancreatic-insufficient and pancreatic-

sufficient patients2) There is a good correlation between the 72-hour fecal output of

chymotrypsin and the CCK secretin–stimulated duodenal output of chymotrypsin

3) Patients receiving pancreatic enzyme supplements should discontinue them at least 5 days prior to measurement

b. Elastase 1 1) More sensitive and specific than fecal chymotrypsin in detecting pancreatic

insufficiency2) A decline in fecal elastase concentration precedes fat malabsorption in

patients with pancreatic-sufficient cystic fibrosis, who become pancreatic insufficient

3) The measurement is not altered by pancreatic enzyme supplementsa) The ELISA is specific for human elastase, so exogenous pancreatic

enzyme supplements, which are of porcine origin, have no effect on the results

4) False-positive results may occur if there is villous damagea) These patients may have a secondary pancreatic insufficiency due

to the impairment of mucosal release of pancreatic secretagogues5) False-negative results may occur with the following

a) Diarrheal disease and short bowel syndrome—secondary to a dilutional effect, which can be overcome by lyophilization of stool samples to remove the water content

b) Occasionally in pancreatic-sufficient patients with Shwachman-Diamond syndrome


2. Advantagesa. Noninvasive b. Does not require administration of oral substrates

3. Disadvantagesa. Only detects severe pancreatic dysfunction

D. NBT-PABA and fluorescein dilaurate tests1. Description

a. Requires oral ingestion of the synthetic peptide NBT-PABA (N-benzoyl-L-tyrosyl-p-aminobenzoic acid) or fluorescein dilaurate with a meal and subsequent measurement of PABA or fluorescein in the serum or urine

b. NBT-PABA is specifically cleaved by chymotrypsin to NBT and PABA; PABA is then absorbed in the intestine, conjugated in the liver and excreted in the urine

c. Fluorescein dilaurate is hydrolyzed by pancreatic carboxylesterase into lauric acid and free water-soluble fluorescein; fluorescein is absorbed into the intestine, partially conjugated in the liver and excreted in the urine

2. Advantagesa. Simple indicator of severe pancreatic dysfunction

3. Disadvantagesa. Tests do not detect mild or moderate pancreatic dysfunctionb. Prior gastric surgery, small bowel disease, liver disease and renal insufficiency may

interfere with the measurementsIV. Blood tests

A. Serum amylase1. Non-specific test of the amount of pancreatic amylase secretion; most clinical

laboratories do not distinguish between salivary and pancreatic isoenzymesB. Serum lipase

1. After 5 years of age, the test is 95% sensitive and 85% specific for the detection of pancreatic insufficiency in cystic fibrosis

2. There is no information about the usefulness of the test in delineating pancreatic insufficiency in other pancreatic diseases of childhood

C. Serum immunoreactive trypsinogen (IRT)1. In infants <1 year of age, elevated IRT is a sensitive diagnostic screening test for cystic

fibrosis with a detection rate of 90%a. IRT levels may be lower in cystic fibrosis infants with meconium ileus compared to

other infants with cystic fibrosis, which can lead to a false-negative screen2. In patients over the age of 7 with cystic fibrosis, decreased serum levels of IRT are highly

predictive of pancreatic insufficiencya. Below 7 years of age, a fecal fat determination is recommended

3. In patients with other pancreatic diseases of childhood, this test is useful in distinguishing pancreatic steatorrhea from nonpancreatic steatorrhea

a. In Shwachman-Diamond Syndrome, IRT values are low because pancreatic failure is due to hypoplasia and reduced acinar enzyme production

Recommended Reading

Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Philadelphia, PA: Saunders Elsevier;2010:909-930.

Kleinman RE, Goulet O-J,Mieli-Vergani, Sanderson IR, Sherman PM, eds. Walker’s Pediatric Gastrointestinal Disease. 5th ed. Lewiston, NY: BC Decker Inc.; 2008:1401-1410.


9D-5. Additional Studies—Breath Tests

Julia Bracken, MDJose Cocjin, MD

I. Hydrogen breath testing Hydrogen breath testing is a safe, noninvasive method to evaluate for sugar malabsorption (lactose,

fructose, sucrose, sorbitol, d-xylose) and small bowel bacterial overgrowth.

II. Testing for Sugar MalabsorptionA. Method

1. While NPO a test dose of specified sugar is administered orallya. Lactose is dosed 2 g/kg with max dose of 25 g

2. Exhaled breath hydrogen content is measured at baseline and every 30 minutes for 3 hours

B. Interpretation1. Pre and post test-sugar hydrogen concentrations are compared

a. Breath hydrogen change of <10 parts per million (ppm) is considered normalb. Breath hydrogen change of >20 ppm is considered diagnostic of sugar

malabsorptionC. Additional Consideration

1. False-positive results: inadequate fasting time, recent smoking2. False-negative results: recent antibiotic use, restrictive lung disorders

III. Testing for Small Bowel Bacterial Overgrowth (SBBO)A. Method

1. While NPO a test dose of a carbohydrate solution is administered orallya. Lactulose is most commonly used (2 g/kg, max 50–75 g)b. Glucose may be used as an alternative substrate

2. Exhaled breath hydrogen content is measured at baseline and every 30 minutes for 3–5 hours

B. Interpretation1. Patients with SBBO demonstrate an early peak in breath hydrogen concentration

a. Lactulose should normally be metabolized by colonic bacteria only2. In SBBO, small bowel bacteria metabolize the substrate prematurely leading to an early

rise (within the first 2 hours) in hydrogen concentration, followed by the expected (and larger) colonic peak

C. Additional Considerations1. Methane-producing bacteria may give false-negative breath hydrogen test results as

hydrogen is converted to methanea. Methane concentrations can be measured concurrently with exhaled hydrogen to

improve sensitivity and detect methane producing bacteriab. Most updated equipment has the capability to measure both gases

2. Short bowel syndrome or fast transit time may give false positive results

Recommended Reading

Hamilton LH. Breath Tests and Gastroenterology. 2nd ed. QuinTron Instrument Company; 1998.

Romagnuolo J, Schiller D, Bailey RJ. Using breath tests wisely in a gastroenterology practice: an evidence-based review of indications and pitfalls in interpretation. Am J Gastroenterol. 2000;97:1113.


9E-1. Laboratory Evaluation—Alkaline Phosphatase

Emily Contreras, MDRebecca Cherry, MD

I. Alkaline phosphatase Alkaline phosphatase (AP) is a group of isoenzymes that hydrolyze organic phosphate esters at alkaline

pH. Serum AP may have many different tissue sources, including liver, bone, placenta and, less often, intestine. The function in the serum is unknown. Levels are often obtained in the evaluation of cholestasis.

II. BackgroundA. Found in several different tissues:

1. Canalicular membrane of hepatocytes – unknown function but may be involved in transport processes

2. Bone osteoblasts – involved in calcification3. Brush border of small intestine enterocytes – involved in cholesterol breakdown and

calcium absorption, can be increased after a fatty meal4. Proximal convoluted tubules of the kidney5. Placenta6. White blood cells

B. Isolated elevated AP does not indicate hepatic or biliary disease if other liver biochemical tests are normal

1. Polyacrylamide gel electrophoresis (not routinely available in all clinical labs) can be used to differentiate between liver, bone, intestinal and placental isoenzymes

C. Level varies with age and sex1. In children, serum AP activity is elevated in both sexes, correlating with rate of bone

growth2. Healthy adolescent males can have AP values >3x normal without underlying

hepatobiliary disease3. From ages 15–50, AP is slightly higher in males4. Over age 60, AP activity is greater in women

III. Alkaline Phosphatase and Hepatobiliary DiseaseA. If AP is elevated, should check gamma glutamyltransferase (GGT) or 5’-nucleotidase (5’NT) to

confirm hepatic origin1. GGT and 5’NT are both present in liver and multiple other organs, but not in bone,

intestine or placentaB. Elevated hepatic AP is due to increased de novo synthesis of AP in the liver induced by bile acids

and subsequent leakage into the serumC. In 75% of patients, biliary obstuction lead to >4x normal AP levels

1. But 25% of adults with viral hepatitis without biliary obstruction can also have AP levels >4x normal

D. AP levels up to 3x normal are nonspecificE. AP levels do not differentiate between extrahepatic or intrahepatic obstruction or between

different etiologies of biliary obstructionF. Markedly increased AP levels are predominantly seen in infiltrative liver disorders (such as primary

or metastatic liver tumors) or with biliary obstruction1. However, AP may be normal despite extensive hepatic metastasis or large biliary

obstructionG. Elevated intestinal AP can be caused by liver disease, such as alcoholic cirrhosis


IV. Non-hepatobiliary Diseases Associated With Elevated APA. Pregnancy: due to increased placental activityB. Familial inheritanceC. Chronic renal failureD. Patients with the following hematologic characteristics have increased intestinal AP:

1. Blood groups type B and type O2. ABH red blood cell antigen 3. Lewis antigen positive

E. Transient hyperphosphatasemia of infancy and childhood: a benign condition characterized by marked increase in serum AP (often >10x normal) lasting up to 8–12 weeks in absence of any clinical, radiologic or biochemical evidence of bone or liver pathology

F. Malignant tumors without any liver involvement1. Regan isoenzyme is produced and indistinguishable from placental AP

V. Low Serum Alkaline PhosphataseA. Zinc deficiency: because Zn is a cofactor for AP, AP activity is low when zinc is deficientB. Wilson disease: AP can be low in fulminant Wilson disease, mechanism unknown

Recommended Reading

Kaplan MM. Alkaline Phosphatase. New Engl J Med. 1972;62:200-202.

Kaplan MM. Alkaline phosphatase and other enzymatic measures of cholestasis. In: Chopra S, ed. UpToDate. Waltham, MA: 2010.

Ng VL. Laboratory Assessment of Liver Function and Injury in Children. In: Suchy FJ, Sokol RJ, Balistreri WF, eds. Liver Diseases in Children. 3rd edition. New York, NY: Cambridge University Press; 2007: 165-166.


9E-2. Laboratory Evaluation—Hematologic Manifestations

of GI Disease

Megan E. Gabel, MDThomas Rossi, MD

I. Complete Blood Count (CBC) Changes in the CBC can be seen related to chronic or acute disease, due to blood loss or due to chronic

medications.

II. Basic Review of AnemiaA. Etiology

1. Decreased production of erythrocytes a. Normocytic: nutritional deficiency, chronic diseaseb. Macrocytic: vitamin B

12 deficiency, folate deficiency, drug related (trimethoprim-

sulfamethoxazole, methotrexate, 6-mercaptopurine), chronic diseasec. Microcytic: iron deficiency, chronic disease

2. Acute blood loss. Usually normocytic3. Chronic blood loss. Usually microcytic4. Increased destruction/consumption

a. Immune mediated, red cell membrane defects, hypersplenismB. General Laboratory Evaluation for Anemia

1. CBC with platelets and differential (includes MCV, RDW), reticulocyte count, blood smear

a. If Microcytic: iron, TIBC, transferrin saturation, ferritin, lead levelb. If Macrocytic: vitamin B

12, folate, TSH

c. If Hemolysis: T/D bili, LDH, Coombs, PT, PTT, haptoglobin, fibrinogen

III. Anemia of Chronic DiseaseA. Most often a mild, normocytic, normochromic anemia associated with a myriad of chronic

illnesses1. In 20% of cases anemia is severe (Hgb <8 g/dL)

B. Characterized by:1. Low serum iron2. Low serum transferrin (TIBC)3. Normal or increased ferritin level (acute phase reactant)4. Low reticulocyte count

C. Pathogenesis is complex and multifactorial1. Increased macrophages production of IL-6 leads to increase in hepatic hepcidin

production2. Hepcidin inhibits intestinal iron absorption and decreases release of iron from

macrophages3. Decrease in erythropoetin production relative to degree of anemia also complicates

some chronic disease4. Decreased RBC survival may play minor role

D. First principle of treatment is control underlying disease1. Rule out other contributing factors such as blood loss or deficiency of iron, B

12 or folate

2. Erythropoietin administration may be effective in some cases


IV. Medications Associated With Macrocytic AnemiaA. Trimethoprim-sulfamethoxazole

1. Trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate2. Sulfamethoxazole interferes with bacterial folic acid synthesis by inhibition of dihydrofolic

acid formation from para-aminobenzoic acid3. Coadministration of folinic acid can mitigate antifolate activity without interfering with

antimicrobial actionB. Methotrexate

1. Methotrexate irreversibly binds to dihydrofolate reductase, inhibiting production of reduced folates

2. Usual finding is macrocytosis, rarely pancytopenia3. Monitor CBC every 4–8 weeks 4. Folic acid can be given if cytopenia develops, but folic acid may decrease methotrexate

efficacyC. 6-Mercaptopurine

1. 6-MP: purine antagonist which inhibits DNA and RNA synthesis2. May cause lymphopenia, anemia, thrombocytopenia3. Recommended screening: CBC weekly for 1 month, biweekly for 1 month, then every

1–2 months during therapy4. Dose should be decreased or discontinued if bone marrow suppression occurs

V. Changes in CBC Due to Inflammatory Bowel DiseaseA. Anemia commonly present at time of IBD diagnosis (78%)

1. May be due to iron deficiency (58%), folic acid deficiency, vitamin B12

deficiency, hemolysis (drug-induced or autoimmune) or chronic disease

2. Complete correction of anemia is associated with significant improvement in quality of life

B. Recommended evaluation of anemia includes total body iron status, transferrin saturation and ferritin

C. Bone marrow suppression may be seen (leukopenia) with 6-Mercaptopurine or methotrexateD. Immune activation may result in suppression of erythrocyte production and thrombocytosis

VI. Hematologic Abnormalities Associated With Liver DiseaseA. Bleeding disorders

1. Liver synthesizes clotting factors II, V, VII, VIII, IX, X2. Vitamin K dependent proteins include factors II, VII,IX, X; protein C, S3. Hypersplenism associated with portal hypertension produces thrombocytopenia 4. Diagnosis: prolongation of PT, INR, specific factor assay, platelet count5. Treatment/Management

a. Vitamin K administration, FFP, cryopreciptate and plateletsb. Recombinant-activated factor VII can be used to correct INR prior to invasive

proceduresB. Hypercoagulopathy occurs due to decrease hepatic synthesis of anticoagulant factors (protein C,

S, antithrombin)1. This is not reflected in the PT, PTT, INR2. Specific factor analysis necessary

C. Portal Hypertension1. Hypersplenism can result in pancytopenia

a. Up to 90% of platelets can be sequestered in the spleenb. Diagnosis based on thrombocytopenia, enlarged spleen

D. Morphologic changes in RBCs (acanthocytes, echinocytes, target cells) can be seen in liver disease

1. Abnormal high density lipoprotein binds to receptors on the RBC membrane and induces conformational change


VII. Other GI Causes of Abnormalities in the CBCA. Vitamin B

12 malabsorption with megaloblastic anemia

1. Due to intrinsic factor deficiency, bacterial overgrowth, pancreatic insufficiency, or ileal resection or disease

B. Celiac disease1. May present with microcytic anemia unresponsive to iron therapy2. May present with pernicious anemia, autoimmune thrombocytopenia

C. H pylori1. Unexplained iron deficiency anemia may be presenting feature2. H pylori infection can result in hypochlorhydria and decreased gastric ascorbic acid levels

that impair bioavailability of dietary ironD. Shwachman Diamond syndrome

1. Pancreatic insufficiency, neutropenia and metaphyseal dysotosis2. Recurrent neutropenia is the most common (>90%), pancytopenia occurs in 10%–25%

of cases3. 1/3 develop myelodysplastic syndrome4. 10%–25% develop acute myeloid leukemia

E. Wilson disease1. Severe hemolytic anemia may occur as hepatocellular necrosis, resulting in the release of

copper ions into the circulationF. Abetalipoproteinemia

1. Very low serum cholesterol2. Near absence of apolipoprotein B containing lipoproteins in the plasma3. Red cell takes the form of acanthocytes (in severe cases up to 90% of RBCs)4. Patients are not anemic and have no evidence of hemolysis

G. Vitamin E deficiency1. Echinocytosis

Recommended Reading

Pels L. Slow hematologic recovery in children with IBD-associated anemia in cases of expectant management. J Pediatr Gastroenterol Nutrition. 2010; 51(6):708-713.

Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver Disease. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2006: Chapters 26,33,38,40.


9E-3. Laboratory Evaluation—Testing for Micro-organisms

Sonal S. Desai, MD Susan S. Baker, MD, PhD

I. Laboratory evaluation Can be used to identify bacterial, viral and parasitic pathogens

A. Helicobacter pylori (see section on Helicobacter Pylori)1. IgG antibodies indicate past or ongoing infection2. H pylori antigen in stool by ELISA very sensitive indicator of ongoing infection3. Gastric mucosal biopsy

a. Warthin Starry or H&E stain shows organisms on surface of gastric mucosab. CLO test (Campylobacter-like organism) – mucosal biopsy placed in urea-

containing medium. Urease activity of H pylori rapidly produces NH3, which

raises pH and produces pink color when positive4. C13 urea breath test – labeled urea given by mouth, labeled CO

2 detected in exhaled

breath. Positive test indicates urease producing H pyloriB. Bacterial diarrheas

1. Salmonella and shigella: stool culture on blood, MacConkey, EMB* or XLD* agar2. E coli – Stool culture on MacConkey, EMB or SM* agar3. Campylobacter jejuni – stool culture on Skirrow agar4. Yersinia enterocolitica – stool culture on CIN* agar. Can be isolated from throat, lymph

nodes, urine and bile5. C dificille

a. Culture on CCFE* agarb. ELIZA for toxin A and Bc. Cell culture of monkey kidney cells with ultrafiltrate of stool reveals characteristic

cytopathic changes caused by toxin B on microscopic examinationd. Immunoassay for glutamate dehydrogenase in stool is rapid and accurate

C. Protozoal1. Giardia lamblia

a. Detect trophozoites in duodenal aspirateb. Detect cysts in stool (least sensitive)c. Detect trophozoites on surface of duodenal biopsyd. Detect giardia antigen in stool (most sensitive)

2. Cryptosporidium sppa. Stool acid-fast stainb. Direct fluorescent antibody on stoolc. ELIZA on stoold. Stain of intestinal biopsy

3. Entameba histolyticaa. Detect in stool or stool concentrate after stainingb. Detect in biopsy from edge of colon ulcersc. PCR and ELIZA on stool possible

4. Blastocystis hominisa. Detect stool hematoxylin or trichrome stain

5. Balantidium colia. Detect by stool examb. Detect by biopsy

6. Isospora bellia. Detect by O&Pb. Detect in duodenal aspiration


D. Nematodes1. Enterobius vermicularis (pinworm)

a. Direct observation of adult worms on perianal skinb. Detect ova microscopically on scotch tape swab of perianal skinc. Stool examination for ova

2. Ascaris lumbricoides, Trichuris trichura, Strongyloides stercoralis, Ancylostoma duodenale (hookworm), Cestoides and Necator americanus (hookworm) – direct stool examination for ova and/or adult forms

3. Cestodes (tapeworm) a. Direct stool examination for proglottids (section of tapeworm) and ovab. Purged stool increases sensitivity of test

4. Trematodesa. Fasciola – stool for ova or ELIZA on bloodb. Schistosomes

1) S mansoni and S japonicum – stool of ova 2) S hematobium – urine for ova3) Serology also used in light infestations

E. Hepatic infections and infestations – (see section on Viral Hepatitis)

*CCFE – cycloserine-cefixitin-fructose-egg agar; CIN – cefsuladin-irgasan-novobiocin agar; EMB – e-methyline blue agar; SM Sorbitol-MacConkey agar; XLD – xylose-lysine-deoxycholate agar.

Recommended Reading

Centers for Disease Control. Available at www.cdc.gov.

Committee for Infectious Diseases. Red Book 2009. Elk

Grove Village, IL: American Academy of Pediatrics; 2009.


9E-4. Laboratory Evaluation—Stool Analysis

Paul Ufberg, MD

I. Stool Analysis Analysis of stool can be helpful in narrowing the differential diagnosis in patients with diarrheal

disease and children with poor growth. Laboratory testing is currently available for fecal fat, stool pH, electrolytes, α-1-antitrypsin, trypsin elastase, reducing substances, fecal blood, WBC, and culture and ova and parasite analysis. Many laboratories now offer fecal calprotectin testing to evaluate for inflammation (see section on IBD).

II. Fecal Reducing SubstancesA. Use of Benedict’s reagent (Clinitest tablets) on liquid feces is the most common qualitative

method to assess carbohydrate malabsorptionB. Reducing substances are generated by colonic bacterial fermentation of unabsorbed

dietary carbohydrates

III. Limitations of Fecal Reducing SubstancesA. The test assumes that the patient’s diet includes reducing sugars, including glucose, lactose and

fructose, but not sucroseB. Malabsorbed sucrose can be degraded by colonic bacteria to glucose and fructose, resulting in a

positive test

IV. Fecal pH EvaluationA. Stool pH less than 5.5 is indicative of carbohydrate malabsorption (reference range is

typically 6.5–7.5)

V. Limitations of Fecal pH EvaluationA. Stool volume and transit time affect accuracy of the pHB. Bacterial fermentation may give falsely acidic results if the specimen is not analyzed within 1 hour

of collection or properly stored prior to analysis

VI. Microscopic Fecal Fat Evaluation (see section Pancreatic Function Test)A. Helpful in qualitative detection of fat malabsorption and monitoring the efficacy of pancreatic

enzyme supplementation therapy in patients with pancreatic insufficiencyB. A rapid screen can be done via steatocrit or sudan red/black staining

VII. Stool Electrolyte EvaluationA. Stool electrolytes are useful in determining osmotic vs secretory diarrheaB. Fecal osmolarity is approximately 290 mOsm/kg and is isotonic with plasmaC. Carbohydrate malabsorption increases osmolarity due to colonic bacterial metabolism of

undigested sugarsD. Equation for stool osmolarity is:

1. Stool osmolarity = 2[(stool Na+ in mEq/L) + (stool K+ in mEq/L)]2. Normal is <503. Osmotic diarrhea = Osmotic gap >100

a. Osmotic diarrhea is caused by maldigestion and/or malabsorption of one or more nutrients. This creates an osmotic force, which drives water across tight junctions into the lumen

b. If stool Na+ is <60 mOsm and the gap is >125, the diarrhea is likely osmotic


4. Secretory diarrhea = Osmotic gap <100a. Secretory diarrhea results from active secretion from epithelial cells. Most acute

causes are from bacterial infections. After colonization, enteric bacteria may adhere to the epithelium and produce enterotoxins or cytotoxins. Cytotoxins attract inflammatory cells contributing to secretion

b. If stool Na+ is >90 and the gap is <50, diarrhea is likely secretory5. In mixed osmotic and secretory diarrhea and cases of modest carbohydrate

malabsorption the osmotic gap is between 50–100 and the stool Na is between 60-90 mEq/L

Table 1. Features of Diarrhea

Osmotic Secretory

Stool Volume moderate increase very large

Response to Fasting stops continues

Stool Osmolarity normal to increase normal

Osmolarity >100 mOsm/kg <100 mOsm/k

E. Fecal electrolytes may be useful in differentiating congenital diarrheas, but are only completely diagnostic in congenital chloride diarrhea

1. Normal Stool:a. Stool Na+ = 20-50 mmol/Lb. Stool K+ = 83-95 mmol/Lc. Stool Cl− = 5-25 mmol/Ld. Osmotic Gap = 50-100 mmol/L

2. Microvillous Inclusion Disease:a. Stool Na+ = 79 mmol/Lb. Stool K+ = 19 mmol/Lc. Stool Cl− = 70 mmol/Ld. Osmotic Gap = <84 mmol/L

3. Intestinal epithelial dysplasia:a. Stool Na+ = 70–120 mmol/Lb. Stool K+ = 22 mmol/Lc. Stool Cl- = 33 mmol/L

4. Congenital Chloride Diarrhea:a. Stool Na+ = 55 ± 27 mmol/Lb. Stool K+ = 56 ± 20 mmol/Lc. Stool Cl− = 158 ± 16 mmol/Ld. Fecal Na + K is less than fecal Cl

5. Congenital Sodium Diarrhea:a. Stool Na+ = 98–190 mmol/Lb. Stool K+ = NOT REPORTEDc. Stool Cl− = 84–109 mmol/Ld. Fecal K + Cl is less than fecal Na

F. Genetic testing is available1. Microvillus inclusion: Mutation in myosin promoter gene MY05B2. Congenital chloride diarrhea: SCL26A3 gene mutation3. Congenital sodium diarrhea: SPINT2 gene mutation4. Intestinal epithelial dysplasia: Mutation in 2p21 epithelial adhesion molecule

VIII. Limitations of Stool ElectrolytesA. Bacterial fermentation following stool collection results in increased stool osmolarityB. Healthy children may ingest nonabsorbable sugars, resulting in increased osmolarity


IX. Other Stool TestsA. Stool α-1-antitrypsin

1. Screening for protein-losing enteropathya. Increased risk after Fontan procedure (4%–13% will get PLE)

2. Levels >5 mg/gm (dry sample) stool is abnormalB. Stool elastase (see section on Pancreatic Function Test)

1. Screen for pancreatic exocrine insufficiencyC. Stool Hemoccult evaluation

1. Identifies occult blood in the stool2. Rely on the oxidative conversion of a colorless compound to blue color in the presence

of pseudoperoxidase activity of hemoglobin3. False-positive with ingestion of raw meat and vegetables with peroxidase properties4. False-negative with citrus and vitamin C ingestion

D. Stool WBC1. Presence of WBC may indicate invasive bacterial infection

E. Stool microbiologic evaluation1. Stool culture for bacteria

a. Place stool on agar or in broth for cultureb. Most labs test for Campylobacter, Escherichia coli O157:H7, salmonella, and

shigella c. Special request for Yersinia and non-O157:H7 Shiga toxin–producing E coli,

Vibrio, Aeromonas and Pleisiomonas2. Stool O&P for parasites

a. Wet mount microscopic examb. Identify Giardia lamblia, Cryptosporidium parvum and Entamoeba histolytica and

helminths3. Stool electron microscopy for viral particles4. Stool viral culture

F. Stool testing for C difficile1. Enzyme immunoassay for toxin A and B2. Multiple specimens do not increase the yield

G. Please see Helicobacter Pylori chapter for stool testing

Recommended Reading

Lindquist BL, Wranne L. Problems in Analysis of faecal sugar. Arch Dis Child. 1976;51:319-321.

Miller JM, Holmes HT. Specimen Collection, Transport, and Storage. In: Murray PR, ed. Manual of Clinical Microbiology, 7th ed. Washington DC: American Society for Microbiology; 1999: 33-104.

Walker WA, Kleinman RE, Sherman PM, Shneider BL, Sanderson IR. Pediatric Gastrointestinal Disease. 4th ed. Hamilton, Ontario: BC Decker, Inc.; 2006:1820.

Wyllie R, Hyams JS, eds. Pediatric Gastrointestinal and Liver Disease. 4th ed. Philadelphia, PA: Saunders Elsevier; 2008: 116.


9F. Radiology Evaluation

Pablo J. Palomo, MDRuben E. Quiros-Tejeira, MD

Lisa Wheelock, MD

I. Introduction Radiology studies play a crucial role in the diagnosis of some conditions. Imaging studies are also used

to direct management in the treatment of other conditions. A clear understanding of the risks and benefits of each modality is vital prior to ordering a specific study. When the optimal testing is unclear, a discussion with a radiologist can be critical to obtaining the correct imaging studies to provide the needed information.

A. Plain abdominal radiograph1. Advantages: low cost, quick, available2. Essential first examination for suspected intestinal obstruction or perforation3. Useful to localize radiopaque foreign bodies4. Evaluation of plain radiographs

a. Identify position of liver, gastric air bubble and cardiac apex to assess for abnormal situs or heterotaxy syndromes

b. Identify abnormal calcificationsc. Assess gas pattern – air fluid level, pneumoperitoneum, pneumatosis intestinalis,

sentinel loops, mass effect1) Differentiation of small and large bowel gas is difficult in neonates

d. Assess bony structures for segmentation anomalies, dysraphisms, sacral dysplasias, fractures

e. Assess diaphragms for hernia, eventrations, paralysisf. Estimate liver and spleen size

B. Abdominal radiographs in specific conditions1. Congenital obstruction

a. Esophageal atresia – gasless abdomen in some forms, coiling of NG tube in esophagus

b. Duodenal atresia – double bubble sign with air in distended stomach and proximal duodenum

c. Jejunal atresia and ileal atresia – dilated loops of small bowel with absence of colon gas

d. Meconium ileus – dilated loops of small bowel with ground glass appearance of stool in right lower quadrant

e. Colon obstruction – dilated loops of colon proximal to obstruction with/without small bowel distension

2. Ileus – non-mechanical obstruction. Air fluid levels and usually less massive bowel distension than mechanical obstruction

3. Viral enteritis – ileus with multiple short air fluid levels, especially in infants. Rarely, pneumatosis occurs in viral enteritis

4. Intraabdominal abscess may produce mass effect, air fluid levels, ileus and obstruction 5. Necrotizing enterocolitis – pneumatosis, pneumoperitoneum, persistent fixed and dilated

bowel loops, portal venous and hepatic pneumatosis may be present6. Ischemia and inflammation cause bowel wall thickening (thumb printing) – inflammatory

bowel disease, shock bowel, infection, lymphoma, GVH, lymphangiectasia, Henoch-Schönlein purpura, hemolytic uremic syndrome, necrotizing enterocolitis and pseudomembranous colitis

7. Hernia may cause bowel gas to appear in abnormal locations – chest, scrotum, umbilicus and inguinal canal


8. Calcificationsa. Adrenal – old hemorrhage, neuroblastoma and Wolman syndromeb. Renal – calculi and Wilms tumor (15% are calcified)c. Pancreas – CF and chronic pancreatitisd. Liver – hepatoblastoma (50%), hemangioendothelioma, hepatocellular carcinoma

and granulomae. Spleen – granulomataf. Appendix – fecalithg. Mesentery – calcified lymph nodes

9. Intussusception – plain radiograph may be normal. Gasless right lower quadrant. Prone film may reveal abnormal cecal gas

C. Barium contrast studies 1. Single contrast (without air), most often used in children, prevents close evaluation of

mucosal abnormalities2. Common indications – congenital and acquired structural GI anomalies, stricture, situs

anomalies, aspiration and inflammatory disease 3. Technical points

a. Use water-soluble contrast when investigating possible perforationb. Use nonionic contrast when tracheal aspiration is possiblec. Use air or water-soluble contrast to evaluate and reduce intussusception

4. Risksa. Swallowing studies performed under direct vision can evaluate all phases of

deglutition. Risk of prolonged fluoroscopy time and radiation exposureb. Upper GI series with small bowel follow through – long duration fluoroscopy

adds to radiation exposureD. Abdominal ultrasound

1. Utilizes frequencies from 1–20 MHz depending on depth of region of interest2. Advantages

a. No ionizing radiationb. Little need for sedationc. Immediate resultsd. Widely available and inexpensivee. Doppler technique allows assessment of blood flow volume and directionf. Improving technology with micro bubble and other contrast is expanding

indications – intraendoscopic, bowel wall anatomy, examination of complex structures, better mucosal detail, better resolution of small structures

3. Disadvantagesa. Poor penetration of air-containing or bony structuresb. Less resolution than CT or MRIc. Operator dependent, time consumingd. Transducer may cause pain over abscess or other painful lesionse. Distal body and tail of pancreas sometimes hard to see

4. Common indicationsa. Modality of choice for pyloric stenosisb. Liver masses, liver vascular anatomy and flow dynamics, gall bladder diseasec. Pancreatic parenchymal, ductular or malignant disease (both extracorporal U/S

and endoscopic ultrasound)d. Bowel wall edema and intussusceptione. Prenatal U/S for duodenal atresia and other anomaliesf. Fluid collections and cystsg. Modality of first choice for scrotum, testes, ovaries, inguinal herniash. Arterial and venous thrombosis – use duplex Doppler ultrasound


E. Computerized tomography (CT)1. Advantages

a. Excellent spatial resolution and tissue differentiation (fluid, soft tissue, calcium, air, fat and iron)

b. Can assess small structures – common bile duct, pancreatic ducts and fistulaec. Can assess bowel wall with use of luminal and intravenous contrastd. Good in suspected abdominal trauma, abdominal masses

2. Disadvantagesa. Very high radiationb. Sedation may be requiredc. Expensived. Oral and intravenous contrast may be contraindicated in renal disease, bowel

obstruction and dehydratione. No possibility of therapeutic intervention, i.e., stone removal, papillotomy,

stricturoplasty3. Technical points

a. No longer recommended as first diagnostic tool in suspected appendicitis (CT with rectal contrast) because of high radiation. Ultrasound is safer

F. Magnetic resonance imaging (MRI)1. Advantages – no radiation with excellent contrast resolution2. Disadvantages

a. May require anesthesia or sedation because of long scan timesb. Expense similar to CTc. Contraindicated with some implantable devices or with unstable patientd. Gadolinium-based contrast contraindicated in renal insufficiencye. Full identification of masses may require multiphase contrast sequences with

lengthy exam time3. Indications

a. Biliary and pancreatic duct anatomy and flow are well describedb. Good substitute for ERCP if intervention is not immediately required c. Excellent for pancreatic abnormalities – divisum, mass, abscess, cystd. MRA/MRV excellent for assessment of vascular anomaliese. MR Enterography

1) Uses gadolinium based IV contrast and luminal contrast2) Dynamic imaging may differentiate active vs inactive disease3) Excellent localization of structural bowel lesions 4) Good mucosal detail

G. Percutaneous transhepatic cholangiography (PTC)1. Requires needle puncture of bile duct – contraindicated in intractable bleeding disorders2. Requires anesthesia for most children3. Helps differentiate surgical from medical causes of cholestasis – choledochal cyst,

choledocolithiasis, stricture (especially if ERCP not possible)4. Used to clarify biliary disease after liver transplant5. Complications – biliary leak, sepsis, cholangitis, hemobilia, fistula6. Some centers routinely give prophylactic antibiotics for Gram-negative and anaerobic

organisms before studyH. Magnetic retrograde cholangiopancreatography (MRCP)

1. Improved MRCP techniques are making endoscopic retrograde cholangiopancreatography ERCP less desirable for diagnosis of biliary disease

2. Advantages – no radiation3. Disadvantages

a. Technical problems in small childrenb. Requires anesthesia in young childrenc. Diagnostic, but not therapeutic

4. Indications – diagnosis and therapy a. Biliary and pancreatic duct strictures, leaks, plugs, stones, cysts and pseudocystb. Evaluation of unexplained pancreatitis and pancreatic trauma

5. Risks: none


I. Radionuclide studies1. Most use compound labeled with Technetium 99m (Tc99m)2. Provides functional information without detailed anatomic evaluation3. Tc99m sulfur colloid used for gastric emptying studies, evaluation of pulmonary aspira-

tion of gastric contents, and motility studies of esophagus4. Tc99m iminodiacetic acid (IDA)

a. Measures amount of hepatic uptake and extent of biliary excretionb. Delayed uptake seen in parenchymal diseasec. Delayed excretion seen in biliary obstruction, biliary hypoplasia, focal biliary

disease of CF, neonatal hepatitis, paucity syndromes, and alpha-1 antitrypsin deficiency

d. Technical details1) Patient must be fasting2) CCK may be used to stimulate gallbladder contraction if there is no risk of

obstructive disease3) Several radionuclides used – IDA, di-isopropyl-IDA (DIPIDA)and

trimethylbromo-IDA (TSIDA)4) Tc99m DIPIDA has >70% hepatic extraction with bilirubin >2mg/dL,

making it the radionuclide of choice in liver disease5) Unclear whether premedication with phenobarbital improves extraction6) Region of interest drawn over gallbladder to serially assess excretion

fraction5. Leukocyte Scintigraphy – tagged WBCs accumulate in areas of inflammation; limited

experience in pediatric GI diseases6. Tc99m albumin – protein-losing enteropathy7. Tc99m pertechnetate for Meckel diverticulum

a. Radionuclide concentrates in gastric mucosa contained in Meckel diverticulumb. Technical details

1) Antihistamines and H2 blockers may prevent excretion of Tc99m, but may also enhance uptake

2) Glucagon reduces peristalsis which improves retention of radionuclide3) Pentagastrin may enhance visualization of diverticulum by enhancing acid

secretionc. False positives – renal and bladder retention of radionuclide, gastric duplication or

cyst, vascular malformations, intussusceptiond. False negatives

1) Poor blood supply to diverticulum2) Insufficient gastric mucosa in diverticulum to concentrate radionuclide3) Idiopathic – repeat examination may be required in difficult cases

8. Tc99m labeled red cell studya. Indications – obscure GI bleedb. Requires active bleeding to detect sitec. Bleed volume required 0.1 mL/minute to be seend. May require imaging for up to 2 hours in slow bleeds


J. Radiation risks of radiologic exams1. Radiation is greater concern in pediatric medicine relative to adult medicine

a. Tissues are more radiosensitiveb. Longer life expectancy to develop radiation induced cancersc. Each exam and radiation dose is cumulatived. Children are 2–10 times more radiosensitive than adults

2. Measures to reduce radiation risk to pediatric patientsa. Assure necessity of test and ideal timing of image acquisitionb. Replace high radiation exposure exams with lower radiation exposure exams or other modalities,

such as MRI or ultrasoundc. Discuss case with radiologist to plan optimal exam to address both clinical concerns and to

minimize radiation exposured. Order based on medical concerns and not on legal or parental pressuree. Assess need for general anesthesia or sedation to decrease need for repeat imaging secondary to

motionf. Be specific in ordering examination to decrease risk of performing incorrect exam and to increase

likelihood that radiology staff may recognize need for specific imaging protocols or possibility of exam with a less radiation exposure

g. Information and data obtained from Image Gently web site through the Society of Pediatric Radiology

Table 1. Diagnostic Procedures

Effective radiation dose in mSva

Number of chest x-rays to give equivalent dose

Time period for equivalent effective dose from estimated natural back-ground radiation in the US

Chest (PA) film .02 1 2.4 days

Upper GI series 3.0 150 1.0 years

Barium Enema 7.0 350 2.3 years

CT of the abdomen 10.0 500 3.3 years

amSv – millisevert

9A. Endoscopy - NASPGHAN

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