Applied Radiology

Dr. Benya is in the Department of Radiology, Section of Pediatric Radiology at the University of Chicago Children's Hospital in Chicago, IL.

Cystic fibrosis (CF) is a common, lethal genetic syndrome caused by mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR).1-3 CFTR encodes for a protein which acts as a cyclic adenosine monophosphate-regulated chloride channel. Impaired chloride conductance leads to abnormal water transport across the apical membrane of epithelial cells.4 Consequently, epithelial cell secretions in patients with CF are increased in viscosity in various organs, including the lungs, bowel, pancreas, and liver. Gastrointestinal pathology occurs in almost all individuals with CF.5 For this reason, awareness of disease processes which may affect the bowel, pancreas, liver, and gallbladder is important in the diagnosis and treatment of children with CF.

Bowel pathology

Meconium ileus-Ten to fifteen percent of children born with CF will present with neonatal bowel obstruction due to meconium ileus.6,7 Meconium ileus results from impaction and obstruction of the terminal ileum by inspissated meconium pellets. Approximately one-half of cases will be complicated with an associated small bowel atresia or stenosis, volvulus, meconium peritonitis, or pseudocyst.6,8 Meconium ileus is diagnosed in the newborn by a contrast enema; diagnostic findings include a microcolon and meconium pellets in the terminal ileum (figures 1 and 2).

Uncomplicated meconium ileus may be treated with a contrast enema.9 As shown by the results from a recent survey of pediatric radiology departments in the USA and Canada,10 the enema techniques and contrast media used in the treatment of meconium ileus varied widely. The rate of successful nonoperative reduction was significantly higher with use of gastrografin and with the use of additives (Tween-80 and Mucomyst) in the contrast material. The osmolality, mode of administration, and catheter size, however, did not correlate with the success rate of nonoperative reduction. Repeat enemas may be necessary to clear the viscous meconium lodged in the distal small bowel. Filling of the dilated ileum, as well as the colon, increased the success rate of nonoperative therapy.10

Distal intestinal obstruction syndrome-Children or adolescents with CF who have distal intestinal obstruction syndrome (DIOS), also referred to as meconium ileus equivalent, typically will present with abdominal pain and obstruction. The prevalence of DIOS in CF ranges from 10% to 47%;5,11 it has not been found to be more common in individuals who had meconium ileus as a neonate.12 In this disorder, thick bowel contents in the terminal ileum and cecum cause a partial or complete distal intestinal obstruction. Inspissated intestinal secretions, undigested food, dysmotility, dehydration, and noncompliance with pancreatic enzyme replacement therapy could all play a role in its occurrence.5,11

Abdominal films will show marked fecal material in the right abdomen with partial or complete small bowel obstruction (figure 3). DIOS may be treated with oral administration of gastrografin,13 N-acetylcysteine, or intestinal lavage solution, or by gastrografin or N-acetylcysteine enema (figure 3).5,11

Intussusception-While intussusception is an uncommon complication in children with CF, only occurring in approximately 1% of cases,14 it must be considered in the child with CF who presents with abdominal pain and/or signs of obstruction. Blood in the stools is not typically seen. The etiology is believed to be adherent fecal material which acts as a lead point to produce an intussusception, most commonly ileocolic. Diagnosis of intussusception may be made by ultrasound or contrast enema examination (figure 4).

Contrast enema reduction should be attempted in the appropriate clinical setting.14

Colonic stricture-In 1994, Smyth and colleagues15 reported a series of cases of children with CF who presented with intestinal obstruction that failed to respond to medical management. At surgery, these patients were found to have stricture of the ascending colon with mucosal and submucosal fibrosis. Additional reports followed,16-18 and the term fibrosing colonopathy was coined to describe this condition. Histologically, these lesions differ from Crohn's disease, which also may occur with increased incidence in children and adults who have CF.19

The etiology of these strictures is not definitively known. The use of high-strength, enteric-coated pancreatic enzymes has been implicated as a possible causative factor in their development; however, not all patients found to have colonic strictures had received high-concentration pancreatic enzymes.17,19 Predisposing factors for the development of irreversible colonic stricture appear to include young age, previous intestinal surgery, and prolonged administration of high-dose lipase products.19

Colonic strictures are characterized by mucosal irregularity, nodular thickening, loss of haustral markings, and longitudinal shortening of the colon with focal or diffuse narrowing appreciated on barium enema (figure 5).18 These strictures appear to begin in the region of the cecum and ascending colon but may extend into the distal colon and rectum. Acute inflammatory changes in the colon usually are minimal or absent.18 However, Ablin and Ziegler20 reported a case of an ulcerative-type colitis in a child who was being given high-strength pancreatic enzymes.

Mucosal abnormalities-The mucosal appearance of the duodenum in older children and adolescents with CF frequently is abnormal; typical findings include thickened folds and nodular filling defects on upper gastrointestinal series, possibly due to retained, abnormally thick mucus or inflamed mucosa caused by unbuffered gastric acid in the duodenum (figure 6).6,21 The small bowel also may show evidence of thickening and distortion of mucosal folds, and a redundant mucosal pattern may be seen in the colon (figure 7).6,21

Gastroesophageal reflux-Pathologic gastroesophageal reflux (GER) is commonly associated with CF (figure 8). In a study by Cucchiara and colleagues,22 the predominant mechanism of reflux in CF patients was transient inappropriate lower esophageal sphincter relaxation. Recognition and treatment of GER in CF patients is especially important because it can exacerbate existing pulmonary problems.11

Pneumatosis intestinalis-The presence of intramural gas in the bowel wall, known as pneumatosis intestinalis (PI), is associated with many chronic lung diseases, including CF (figure 8). The development of PI is believed to occur as a result of air block phenomena following the dissection of air into the pulmonary interstitium, the mediastinum, and along vascular sheaths, terminating in the bowel wall. Hernanz-Schulman et al23 reported that pneumomediastinum, pneumothorax, or pulmonary interstitial emphysema was found in 95% of CF patients with PI, and only 62% of CF patients without it.

Rectal prolapse-In one series of 605 children with CF, rectal prolapse was found to occur in 18.5%.24 Most cases of rectal prolapse in the United States are not related to CF but rather to acute diarrhea, chronic constipation, or neurologic/anatomic defects.25 Nonetheless, it is important to recognize that rectal prolapse may occur prior to the diagnosis of CF and, thus, when a child presents with rectal prolapse and no other associated diseases, a sweat chloride test should be performed to exclude cystic fibrosis.25

Pancreatic pathology

Pancreatic insufficiency-Eighty-five percent of children with CF have evidence of exocrine pancreatic insufficiency5 with symptoms of fat- and protein malabsorption and fecal loss. In CF patients, the pancreatic ducts often become obstructed by secretions containing an increased concentration of protein. Over time, this obstruction leads to acinar atrophy with replacement of the pancreas by fatty- and fibrous tissue and resultant pancreatic exocrine gland dysfunction. The extent of pancreatic involvement does not appear to correlate with the severity of pulmonary disease.26

A spectrum of changes may be appreciated when imaging the pancreas of an individual with CF. Sonographic studies of the pancreas frequently show diffusely increased echogenicity due to fatty replacement (figure 9A).27,28 CT examination also may show complete or partial replacement of the pancreas by fat (figure 9B).28 Additional findings may include calcifications,27,28 microcysts, and, rarely, macrocysts (figure 10).29 Tjon A Tham and colleagues26 described three patterns of pancreatic change on MR imaging: 1) a lobulated, enlarged pancreas with complete replacement by fatty tissue; 2) a small, atrophic pancreas with partial replacement by fatty tissue; and 3) diffuse atrophy of the pancreas without fatty replacement.

Abdominal pain-acute or chronic-may be due to pancreatitis and is most frequently seen in those individuals with some residual pancreatic function.30

Gallbladder pathology-The gallbladder of individuals with CF frequently shows abnormalities on imaging studies; the likelihood of finding such abnormalities increases with the age of the patient. The gallbladder often is imaged as small and shrunken (figure 11), containing thick, colorless bile.5 Additional abnormalities include the presence of sludge and/or gallstones in the gallbladder. In a study by L'Heureux et al, gallstones were found to be present in 11.9% of CF patients who underwent oral cholestography;31 these also may be identified sonographically. Possible etiologies for gallstone formation include interrupted enterohepatic circulation due to ileal resection in children with meconium ileus, or with DIOS and resultant ileal dysfunction.32

While CF patients with gallstones and gallbladder pathology may develop cholecystitis,7 these functional and anatomic abnormalities of the gallbladder usually are not associated with any symptoms.5

In a review of sonograms performed on 27 children with CF, Quillin and colleagues33 found 33% of these children had gallbladder abnormalities including small gallbladders and the presence of sludge in the gallbladder. In their series, the investigators found no gallbladder wall thickening or gallstones.

Liver pathology-Focal biliary cirrhosis is recognized on liver biopsy and autopsy specimens in 50% of individuals with CF,34 though only 4% to 6% of CF patients manifest symptoms of cirrhosis and portal hypertension.7 Three histologic patterns of liver disease have been identified in CF: steatosis, focal biliary fibrosis, and multilobular cirrhosis.33,35 Of the three, only focal biliary fibrosis is specific for CF.33

At sonography, the liver may show increased echogenicity (figure 12A), periportal hyperechogenicity, heterogeneous echogenicity,33 and nodularity.35 On CT examination of the liver, low attenuation due to fatty infiltration (figure 12b) or cirrhosis (figure 13) may be identified. It has been suggested that imaging findings in the liver may reflect the histologic changes of steatosis, biliary fibrosis, and cirrhosis.33 AR

References

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