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Gastrointestinal manifestations of cystic fibrosis
Gastrointestinal By Sara
J. Abramson,
Manifestations David
H. Baker,
John
YSTIC FIBROSIS (CF) involves the gastrointestinal (Cl) tract with differing clinical manifestations at ages that range from in utero to adulthood. This report concentrates on the varying patterns of abdominal findings seen in the different age groups.
OBSTRUCTION-MECONIUM AND
ITS
B. Amodio,
and
Walter
E. Berdon
produced in mucous glands of the GI tract and the lack of normal pancreatic enzymes.‘,’ Plain films of the abdomen reveal irregularly dilated loops of bowel with a “soap bubbly” appearance4 and absence of air-fluid levels on erect or decubitus films (Fig 1).5,6 The bubbly
C
INTESTINAL
of Cystic Fibrosis
From Ihe Deparrment of Pediatric Hadiology:y, Babies Hospital. Columbia-Presbyterian Medical Senter. New York. Sara J. Abramson: Assistant Professor. David H. Baker: Professor and Chairman, Department of Radiology. John B. Amodio: Assistanr Professor. Walter E. Berdon: Professor and Director, Pediatric Radiology. Address reprint requests to Sara J. Abramson. MD. Deparimenr of Pediatric Radiology. Babies Hospital, Columbia-Presbyterian Medical Center, 622 W 168 St, New York, NY 10032. % 1987 by Grune & Stratton, Inc.
ILEUS
COMPLICATIONS
In CF, 10% to 157%of patients present in the newborn period with meconium ileus.’ Meconium ileus may occur in complicated and uncomplicated forms. Small bowel obstruction in patients with uncomplicated meconium ileus is the result of inspissation of abnormally viscous meconium at the level of the terminal ileum. The abnormal meconium is the result of thick mucus
0037-198~/87/2202-0005%05.00/0
Fig 1. Newborn with meconium ileus. (A) Supine radiograph of the abdomen reveals multiple loops of dilated bowel with a possible soft tissue mass in the right lower quadrant. Several loops of dilated small bowel cannot be distinguished from colon. (B) Cross table lateral shows multiple dilated loops of bowel with no air-fluid levels, and with absence of gas in the
rectum.
Semmars
,n Roentgendogy,
Vol XXII,
No 2 (April).
1987:
pp 97-l
13
97
ABRAMSON
appearance of the thickened meconium mixed with fluid may not always be present, and airfluid levels are sometimes noted.’ Contrast enema will reveal a microcolon (Fig 2).’ In the past, newborns demonstrating meconium ileus on contrast enema examinations were surgically treated.8 Since 1969, Gastrografin (diatrizoate meglumine and diatrizoate sodium solution [Squibb, Princeton, NJ]) by enema has been used to disimpact the bowel and relieve obstruction.9,‘0 In addition to drawing water into the bowel, the presence of a wetting agent (Tween 80) in Gastrografin probably contributes to flushing of the tenacious meconium from the small bowel. Because Gastrografin is water solu-
ET AL
ble and hypertonic, a large shift of fluid into the bowel commonly occurs. Absorption of Gastrografin solutes may aggravate electrolyte problems.” Intravenous (IV) monitoring of fluid and electrolyte balance during and after the procedure must be carefully maintained. Problems of this sort may be prevented either by diluting the Gastrografin or by increasing the amount of IV infusion. While one enema may be all that is necessary for disimpaction, frequently several enemas are required over the course of three to seven days (Fig 3). While many newborns with uncomplicated meconium ileus may be successfully treated by Gastrografin enema, some still require
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
99
Fig 2. Barium enema in uncomplicated meconium ileus. The classic “microcolon” with normal length, but diminished caliber is shown. The appendix is filled with barium. Multiple dilated airfilled loops of small bowel are identified.
surgic,tl disimpaction. Infants with meconium ileus who survive the initial treatment have the same prognosis as infants with CF without meconium ileus. Complicated meconium ileus is seen in those infants who, in addition to the meconium inspissation, develop secondary volvulus.‘2~‘3 This complication may be present in as many as 50% of patients with meconium ileus. The volvulus may lead to necrosis and perforation secondary to decreased blood supply. Spillage of sterile meconium into the peritoneal cavity results in meconium peritonitis. If the perforation has occurred a sufficient time interval before delivery, the meconium will have calcified and will be evident on plain films of the abdomen.’ In males, calcification in the scrotum may also be seen due to the patent processus vaginalis, which allows free communication between the peritoneal cavity and the scrotum. The loops of bowel involved in
the volvulus may become matted together to form a large mass or pseudocyst, which may contain fluid or air or both.‘,14 The volvulus and accompanying interruption of blood supply to the bowel may lead to areas of bowel resorption and subsequent development of one or more areas of small bowel atresia in addition to the meconium ileus (Fig 4).14-16 There are infants with CF and tneconium peritonitis, but with an intact intestinal tract. whose bowel had obviously perforated in utero only to heal without stenosis. Abdominal or scrotal calcifications provide roentgenographic evidence of the perforation (Fig 5).“.” It is important to remember that the most common cause of meconium peritonitis is perforation from small bowel atresia unrelated to CF. However, underlying meconium ileus and CF should always be ruled out in these patients.” Prenatal diagnosis of CF by measuretnent 01
ABRAMSON
microvillar membrane enzymes in amniotic fluid is under intensive study.” This measurement of fetal GI enzymes in amniotic fluid may be used in the prenatal diagnosis of CF. At the time of amniocentesis, careful real time ultrasonography may reveal abnormalities in the fetal abdomen associated with meconium ileus (Fig 6).19 The presence of an echogenic mass in the fetal abdomen should alert one to the possibility of meconium ileus and CF.2032’ Muller et alI9 noted a 46% incidence of meconium ileus diagnosed pathologically in aborted 17 to I9 week fetuses in whom assays of amniotic microvillar membrane enzymes were abnormal. Some of these fetuses had echogenic masses in the abdomen demonstrated by ultrasonography at the time of amniocentesis (Fig 6). The high incidence of meconium ileus diagnosed by ultrasonography in these fetuses, much greater than the 10% to 15% incidence of meconium ileus in newborns, may be related to the inclusion of both
ET AL
true meconium ileus and transient ileal obstruction in some of these fetuses. Prenatal ultrasonographic findings of meconium peritonitis have been clearly described. Fetal ascites, sometimes loculated, is seen, and echogenic debris in the fluid may be shown.22*23 Calcifications surrounding the fluid may be demonstrated by the identification of intensely echogenic areas with posterior shadowing.24 An inhomogeneous mass, sometimes with echolucent and echogenic components, is often present (Fig 6). 24,25This mass of meconium may have an intensely echogenic rim with posterior enhancement, indicating calification of its border (Fig 7).26 Maternal hydramnios frequently accompanies these findings.‘*23x26 Most patients with CF who present with intestinal obstruction have meconium ileus. However, occasionally, the intestinal obstruction is incomplete and these children develop the meconium plug syndrome or small left colon syn-
GI MANIFESTATIONS
OF CYSTIC
Fig 3.
FIBROSIS
101
(COfl It’d).
drome. ‘h.27.28The meconium plug syndrome is most commonly seen in infants of diabetic mothersz9 or in babies with hypermagnesemia secondary to maternal intake of magnesium sulphate for toxemia.30 Hirschsprung’s disease and CF should also be included in the differential diagnosis. Meconium ileus equivalent, a term coined by Jensen in 1962,3’ refers to obstruction, frequently transient, in the distal small bowel by thick stool, in the older patient with CF.32 In part, it may be due to the absence of exogenous pancreatic enzymes. Therapeutic enemas with N-acetyl cysteine (Mucomyst [Mead Johnson Pharmaceutical, Evansville, IN]) or Gastrografin often relieve the obstruction. Radiographs of the abdomen reveal dilated loops of small bowel, often
with air-fluid levels and a bubbly soft tissue mass in the distal ileum and cecum. The inspissated stool may act as a lead point for intussusception.lh In children with CF, the appendix is sometimes enlarged and edematous and may also intussuscept (Fig 8). ASCITES
Ascites has been mentioned previously in the context of complicated meconium ileus. Ascites may also be secondary to hypoproteinemia from malabsorption.‘h Infants not suspected of having CF often have their formula changed when diarrhea develops. Soy bean formula, which is less allergenic than cow’s milk, is often used. This source of protein has been found to be poorly utilized by infants with CF, and has caused
102
ABRAMSON
Fig 4. Complicated meconium ileus with pseudocyst formation. IA) Supine and (B) lateral with a calcific rim. Note the dilated loops of small bowel and absence of gas in the rectum. atresia.
hypoproteinemia and anasarca. Human milk has a low protein content compared with cow’s milk, so that it too is more apt to lead to hypoproteinemia. CF should be considered in any infant who presents with edema and a normal urine analysis.33
OTHER BOWEL
CHANGES
In older children with CF, the duodenum and small bowel often appear abnormal. Particularly in the duodenum, the mucosal folds may appear thickened and nodular. This may be due to abnormally thick mucus produced by the mucous glands, hypertrophy of Brunner’s gland, or the
radiographs The child
reveal a large had associated
ET AL
mass ileal
increased effect of gastric acid without the normal buffering. Effacement of the duodenal loop may be caused by fatty replacement and distortion of the pancreas.34In older children and adults, the small bowel may be universally involved with markedly thickened and distorted mucosal folds, and mildly dilated loops that appear neither edematous nor separated. Some patients demonstrate severe involvement from the ligament of Treitz to the rectum (Fig 9).35336 Colonic pneumatosisis occasionally shown on abdominal radiographs in children with CF; it is seen at autopsy in 5% to 10% of cases. It is usually asymptomatic. Duodenal ulcer is seen at autopsy in 10% of
GI MANIFESTATIONS
Fig4.
OF CYSTIC
FIBROSIS
103
(‘Cent‘dl.
patients with CF. It is rarely diagnosed during life.‘6,34 HEPATOBILIARY
DISEASE
Hepatobiliary manifestations of CF vary. Neonatal jaundice may be the first sign. Abnormally thick bile may become inspissated in the biliary tree and lead to cholestasis.The diagnosis may be mistaken for biliary atresia. Technetium 99m-iminodiacetic acid (99”Tc-IDA) scanning after pretreatment with phenobarbitol may show no excretion into the GI tract, just as is seen in biliary atresia. In fact, such patients may be
explored for biliary atresia. In one such case, the gall bladder and extrahepatic ducts were found to be filled with abnormally tenacious bile. Once the biliary tract was cleared of this abnormal bile, an operative cholangiogram revealed a normal intrahepatic and extrahepatic biliary tree. A sweat test subsequently performed was abnormal. An enlarged fatty liver may be the presenting sign of CF. Fatty infiltration of the liver may be seenat various times in the course of CF, and is related to protein deficiency. Fat accumulates in the liver when the protein moiety of lipoprotein is
104
ABRAMSON
ET AL
Fig 5. Intact intestinal tract with evidence of meconium peritonitis. (A) Plain radiograph of the abdomen in a child referred for scrotal masses reveals a normal bowel gas pattern. Irregular calcifications in the right upper quadrant indicate previous bowel perforation with meconium peritonitis. (B) Film of the scrotum shows bilateral calcifications.
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
Fig 6. Prenatal sonographic diagnosis of cystic fibrosis with meconium ileus. (A) Longitudinal real time ultrasonogram reveals an irregular echogenic mass in the fetal abdomen (arrows). (B) Autopsy confirmation. Note the dilated loops of small bowel filled with meconium. Microcolon is present. (Courtesy of Dr A. Boue.“)
105
/ ’
Fig 8. lntussusception in CF. Barium enema on a 16year-old with CF who had complained of adbominal pain for e week shows a typical coilspring appearance with mess effect in the cecum. The appendix is seen within the mass. At surgery. the lead mass of the intussusception was the thickened and edematous appendix. The bowel was viable.
Fig 7. Prenatal sonographic diagnosis of meconium peritonitis. The fetal liver (I) is floating in ascitic fluid (a). An echogenic mess (lower arrowhead) is seen, with posterior shadowing. An echogenic rim is present about the abdominal wall (upper arrowhead). h, Fetal heed: p. placenta. IReprinted with permission of Dr David Rochester.“)
Fig 9. Bowel changes in CF. IA) Radiogr bowel the dluodenum and proximal small irregL alar thickening and nodularity o d the du folds. (Bt Delayed film shows distor ?ed and ened folds all through the small bov vel. The affected. colon was similarly
,aph of shows thickentire
Fig 10. Fatty infiltration of the liver in CF. (A) Longitudinal ultrasonogram of liver reveals an enlarged diffusely echogenic liver with poor through transmission. 16) Topogram of CT shows diffuse lucency in the liver, indicating fatty infiltration. (Cl CT of the upper abdomen after oral (but not IV) contrast medium reveals strikingly decreased density of the entire liver.
Fig 11. The gallbladder in CF. This ultrasonogram obtained after fasting shows a small irregular gall bladder (arrows) containing hypoechoic material.
Fig 12. Ultrasonogram reveals gall bladder sludge with posterior shadowing in a 4-month-old infant with malabsorption and abdominal distension. Sweat test was abnormal.
ABRAMSON
ET AL
Fig 13. Transverse ultrasonogram of the upper abdomen in an adolescent with CF. A small echogenic pancreas (outlined by crosses) is shown. S, superior mesenteric artery.
unavailable,3s and when there is depletion of proteinaceous liver enzymes concerned with fat metabolism.39 Fatty liver may occasionally be suspected on abdominal radiographs when lucency in the liver region is apparent.40*4’ More recently, fatty infiltration of the liver has been diagnosed by ultrasonography and CT (Fig 10). On sonography, increased echogenicity of the liver with decreased transmission of sound waves through it suggests fatty infiltration. On CT, fatty infiltration of the liver is clearly shown. The entire liver may reveal decreased density with bright portal venous areas.42 However, patchy fatty infiltration of the liver may also be recognized. Cyst-like changes represent the areas of fatty involvement surrounded by fibrosis.43 Other changes in the liver may be seen on ultrasonography. An enlarged liver or a small irregular liver may be identified in some patients. Irregular echogenicity may be scattered throughout the liver, sometimes in a nodular fashion, or may be most prominent in the periportal areas.44*45 When the liver is small and irregularly echogenic, especially in the periportal areas, biliary cirrhosis is suggested.
Splenomegaly may be seen on sonography. An enlarged splenic vein is sometimes present. These findings suggest portal hypertension. CT of the liver in children with CF may reveal a normal, small, or enlarged liver. Splenomegaly may be present and enlargement of the splenic and superior mesenteric veins may be seen. When a shrunken liver is present along with splenomegaly and visualization of the superior mesenteric and splenic veins, a diagnosis of biliary cirrhosis with portal hypertension is strongly suggested.42 Although this is seldom recognized clinically in CF, liver biopsy and autopsy studies indicate that up to 50% of patients with CF have focal biliary cirrhosis.42.45.46 On sonography, the gall bladder in CF may be normal or sma11.44 Sometimes a tiny shrunken gall bladder is almost indiscernible (Fig 11). Sludge or calculi in the gall bladder may be seen (Fig 12) ?5,47 True calculi may be difficult to identify in a shrunken gall bladder. The pancreas is abnormal in 75% of children under 5 years of age and 95% of children over 5 years of age with CF.45 It shows a variable ultrasonographic appearance (Fig 13). Most
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
Fig 14. Pancreatic cystosis in CF. (AI Longitudinal ultrasonogram area of the pancreas. (B) CT of the same patient shows a large cystic Hernanz-Schulman et alw and N.T. Griscom.)
111
of upper abdomen mass in the area
reveals of the
multiple pancreas.
large cysts in the (Courtesy Drs M.
112
ABRAMSON
commonly, it appears small and echogenic, 44345347x48 sometimes showing pancreatic calcifications. On CT, the pancreas is usually small and replaced by fat.42343349 Some patients with fatty infiltration of the pancreas have clinical diabetes.
ET AL
However, this association is inconstant.50~5’ Scattered cysts are sometimes seen, usually small and in the pancreatic tai1.48.49,52 Giant cystic replacement of the pancreas (pancreatic cystosis) has also been described on sonography and on CT (Fig 14).53
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1948;29:228-236
7. Berdon WE, Baker DH. Santulli TV, et al: Microcolon in newborn infants with intestinal obstruction. Radiology 1968;90:878-885 8. Hiatt R, Wilson P: Celiac syndrome: therapy of meconium ileus. Report of 8 cases with review of the literature. Surg Gynecol Obstet 1948;87:3 17-327 9. Noblet HR: Treatment of uncomplicated meconium ileus by Gastrografin enema: A preliminary report. J Pediatr Surg 1969;4: 190- I97 IO. Wagget J, Johnson DC, Borns P, et al: The nonoperative treatment of meconium ileus by Gastrografin enema. J Pediatr 1970;17:407-41 I 1 I, Rowe MI, Seagram G, Weinberger M: Gastrografin induced hypertonicity. Am JSurg 1973;125:185-188 12. Donnison A, Schwachman H, Gross R: A review of 164 cases with meconium ileus seen at the Children’s Hospital Medical Center, Boston. Pediatrics 1966;37:833-850 13. Holsclaw D, Eckstein H, Nixon H: Meconium ileus: A 20 year review of 109 cases. Am J Dis Child 1965;109:101II3 14. Santulli TV, Blanc WA: Congenital atresia of the intestine. Pathogenesis and treatment. Ann Surg 1961;154:939-948 15. Nixon H: Intestinal obstruction in the newborn. Arch Dis Child 1955;30:13-22 16. Grossman H, Berdon WE, Baker DH: Gastrointestinal findings in cystic fibrosis. AJR 1966;97:227-237 17. Berdon WE, Baker DH, Becker J, et al: Scrotal masse in healed meconium peritonitis. N Engl J Med 1967;277:585587
18. Finkel Ll, Slovis TL: Meconium peritonitis. Intraperitoneal calcifications and cystic fibrosis. Pediatr Radio1 1982; 12:92-93 19. Muller F, Aubrey MD, Gasser B, et al: Prenatal diagnosis of cystic fibrosis. II. Meconium ileus in affected fetuses. Prenat Diagn 1985;5:19-117 20. Denholm T, Crow H, Edward W, et al: Prenatal
sonographic 1984;143:371-372 21. Papp
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Z, Toth Z, Szabo M, et al: Early prenatal of cystic fibrosis by ultrasound. Clin Genet
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senting
Garb M, Riseborogh D: Meconium peritonitis as fetal ascites on ultrasound. Br J Radio1
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Clair M, Rosenberg E, Ram P, et al: Prenatal diagnosis of meconium peritonitis. Prenat
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1983;3:65-68 24. Blumenthal
DH, Rushovich AM, Williams RK, et al: Prenatal sonographic findings of meconium peritonitis with pathologic correlation. J C/in Ultrasound 1982;10:350-352 25. Brugman SM. Bjelland JJ, Thomasson JE, et al: Sonographic findings with radiologic correlation in meconium peritonitis. J Clin Ultrasound 1979;7:305-306 26. Fleisher AC, Davis RJ, Campbell L: Sonographic detection of a meconium containing mass in a fetus: A case report. J Clin Ultrasound 1983;11:103-105 27. Davis W, Allen R, Favara B, et al: Neonatal small left colon. AJR 1974:120:322-329 28. Rosenstein BJ; Cystic fibrosis presenting with the meconium plug syndrome. Am J Dis Child 1978;132:167169 29. Davis W, Campbell JB: Neonatal small left colon syndrome. Am J Dis Child 1975; 129:1024-1027 30. Sokal M, Koenigsberger M, Rose JS, et al: Neonatal hypermagnesemia and the meconium plug syndrome. N Engl J Med
1972;286:823-825
3 1. Jensen K: Meconium patient with mucoviscidosis.
ileus equivalent Acta
Paediatrica
in a I5 year old 1962;5 I :344-
348 32. Cordonnier J, lzant R Jr: Meconium ileus equivalent. Surgery 1963;54:667-672 33. Fleisher D, DiGeorge A, Barness L, et al: Hypoproteinemia and edema in infants with cystic fibrosis of the pancreas. J Pediatr I964;64:34 I-348 34. Phelan M, Fine S, Zentler-Muntro P, et al: Radiographic abnormalities of the duodenum in cystic fibrosis. Clin Radio1
1983;34:573-577
35. Taussig LM, Saldino RM, diSant’Agnese PA, et al: Radiographic abnormalities of the duodenum and small bowel in cystic fibrosis of the pancreas (mucoviscidosis). Radiology 1973;106:369-376 36. Berk RN, Lee FA: The late gastrointestinal manifestations of cystic fibrosis of the pancreas. Radiology 1973;106:377-381 37. Hernanz-Schulman M, Kirkpatrick JA, Schwachman H, et al: Pneumatosis intestinalis in cystic fibrosis, Radiology 1986;
160:497-499
GI MANIFESTATIONS
3X.
Lombardi
OF CYSTIC
B: Considerations
fatty liver. Lab 39. Fletcher
malnutrition. Griscom NT,
visibly 41.
fatty Gilson
liver. B. visible
42. puted
Cunningham tomography
fibrosis
patients.
113
on the
fnvest 1966;15:1-20 K: Observations
infantile 40.
graphically 197?;59:778-780
FIBROSIS
on the
pathogenesis
origin
of liver
characteristic 1980;134:1005-1010
Radiology 1975;177:385-389 Levin D, Currarino G, et al: fatty
liver
DG. in the
Churchill evaluation
J Comput
Assist
Tomogr Reddish
in cystic
appearance
on
WIlsonSharp R. Irving of the pancreas. liver
fibrosis. 46.
Arch Dis diSant’Agnese cirrhosis
Child
adominal
I980;4:
fibrosis:
50. mellitus
Its AJR
associated
with
cystic
type fibrosis
through
and childhood. Swobodnik W,
signs
D, C/in Wolf
of portal
Sauvegrain
hypertension.
J:
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Ultrasound
and
Schwachman
cystic
fibrosis
1962; 104:625-634 5 I, diSant’Agneae
PA,
inal organs in cystic I96 I ;40:64-74
et
al:
of
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Pancreatic S8:629-63
Lepore
fibrosis
I
pancreas.
of abdomGu\trrwnterol
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M. Teele in
J /)i~ Child
DG, Hcnkin RF,. et al: in cystic tibro\is demon-
radiological
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cystic
I : Diabetes Anr
M: Involvement
of the
wtth
et al: Pancreatic appearances.
Kulczycki
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RJ, Cunningham of the pancreas
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strated by multiple I98 1~245172-74 53. Hernanr-Schulman of
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A, Gaskin K, Martin DJ, fibrosis: CT and sonographic
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52. Churchill Macroscopic
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Roentgeno-
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1983;7:530-533 J. Teele RL:
45. graphy
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43. Schwartz A. Dorkin H, Carter B: CT the liver in a patient with biliary cirrhosis and J Compur A.wkt 44. Wili U,
of
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.I ,4 MA
Percr-Ataydra libro\is.
Krrt!io/o,eJ,
A.
J. Abramson,
Manifestations David
H. Baker,
John
YSTIC FIBROSIS (CF) involves the gastrointestinal (Cl) tract with differing clinical manifestations at ages that range from in utero to adulthood. This report concentrates on the varying patterns of abdominal findings seen in the different age groups.
OBSTRUCTION-MECONIUM AND
ITS
B. Amodio,
and
Walter
E. Berdon
produced in mucous glands of the GI tract and the lack of normal pancreatic enzymes.‘,’ Plain films of the abdomen reveal irregularly dilated loops of bowel with a “soap bubbly” appearance4 and absence of air-fluid levels on erect or decubitus films (Fig 1).5,6 The bubbly
C
INTESTINAL
of Cystic Fibrosis
From Ihe Deparrment of Pediatric Hadiology:y, Babies Hospital. Columbia-Presbyterian Medical Senter. New York. Sara J. Abramson: Assistant Professor. David H. Baker: Professor and Chairman, Department of Radiology. John B. Amodio: Assistanr Professor. Walter E. Berdon: Professor and Director, Pediatric Radiology. Address reprint requests to Sara J. Abramson. MD. Deparimenr of Pediatric Radiology. Babies Hospital, Columbia-Presbyterian Medical Center, 622 W 168 St, New York, NY 10032. % 1987 by Grune & Stratton, Inc.
ILEUS
COMPLICATIONS
In CF, 10% to 157%of patients present in the newborn period with meconium ileus.’ Meconium ileus may occur in complicated and uncomplicated forms. Small bowel obstruction in patients with uncomplicated meconium ileus is the result of inspissation of abnormally viscous meconium at the level of the terminal ileum. The abnormal meconium is the result of thick mucus
0037-198~/87/2202-0005%05.00/0
Fig 1. Newborn with meconium ileus. (A) Supine radiograph of the abdomen reveals multiple loops of dilated bowel with a possible soft tissue mass in the right lower quadrant. Several loops of dilated small bowel cannot be distinguished from colon. (B) Cross table lateral shows multiple dilated loops of bowel with no air-fluid levels, and with absence of gas in the
rectum.
Semmars
,n Roentgendogy,
Vol XXII,
No 2 (April).
1987:
pp 97-l
13
97
ABRAMSON
appearance of the thickened meconium mixed with fluid may not always be present, and airfluid levels are sometimes noted.’ Contrast enema will reveal a microcolon (Fig 2).’ In the past, newborns demonstrating meconium ileus on contrast enema examinations were surgically treated.8 Since 1969, Gastrografin (diatrizoate meglumine and diatrizoate sodium solution [Squibb, Princeton, NJ]) by enema has been used to disimpact the bowel and relieve obstruction.9,‘0 In addition to drawing water into the bowel, the presence of a wetting agent (Tween 80) in Gastrografin probably contributes to flushing of the tenacious meconium from the small bowel. Because Gastrografin is water solu-
ET AL
ble and hypertonic, a large shift of fluid into the bowel commonly occurs. Absorption of Gastrografin solutes may aggravate electrolyte problems.” Intravenous (IV) monitoring of fluid and electrolyte balance during and after the procedure must be carefully maintained. Problems of this sort may be prevented either by diluting the Gastrografin or by increasing the amount of IV infusion. While one enema may be all that is necessary for disimpaction, frequently several enemas are required over the course of three to seven days (Fig 3). While many newborns with uncomplicated meconium ileus may be successfully treated by Gastrografin enema, some still require
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
99
Fig 2. Barium enema in uncomplicated meconium ileus. The classic “microcolon” with normal length, but diminished caliber is shown. The appendix is filled with barium. Multiple dilated airfilled loops of small bowel are identified.
surgic,tl disimpaction. Infants with meconium ileus who survive the initial treatment have the same prognosis as infants with CF without meconium ileus. Complicated meconium ileus is seen in those infants who, in addition to the meconium inspissation, develop secondary volvulus.‘2~‘3 This complication may be present in as many as 50% of patients with meconium ileus. The volvulus may lead to necrosis and perforation secondary to decreased blood supply. Spillage of sterile meconium into the peritoneal cavity results in meconium peritonitis. If the perforation has occurred a sufficient time interval before delivery, the meconium will have calcified and will be evident on plain films of the abdomen.’ In males, calcification in the scrotum may also be seen due to the patent processus vaginalis, which allows free communication between the peritoneal cavity and the scrotum. The loops of bowel involved in
the volvulus may become matted together to form a large mass or pseudocyst, which may contain fluid or air or both.‘,14 The volvulus and accompanying interruption of blood supply to the bowel may lead to areas of bowel resorption and subsequent development of one or more areas of small bowel atresia in addition to the meconium ileus (Fig 4).14-16 There are infants with CF and tneconium peritonitis, but with an intact intestinal tract. whose bowel had obviously perforated in utero only to heal without stenosis. Abdominal or scrotal calcifications provide roentgenographic evidence of the perforation (Fig 5).“.” It is important to remember that the most common cause of meconium peritonitis is perforation from small bowel atresia unrelated to CF. However, underlying meconium ileus and CF should always be ruled out in these patients.” Prenatal diagnosis of CF by measuretnent 01
ABRAMSON
microvillar membrane enzymes in amniotic fluid is under intensive study.” This measurement of fetal GI enzymes in amniotic fluid may be used in the prenatal diagnosis of CF. At the time of amniocentesis, careful real time ultrasonography may reveal abnormalities in the fetal abdomen associated with meconium ileus (Fig 6).19 The presence of an echogenic mass in the fetal abdomen should alert one to the possibility of meconium ileus and CF.2032’ Muller et alI9 noted a 46% incidence of meconium ileus diagnosed pathologically in aborted 17 to I9 week fetuses in whom assays of amniotic microvillar membrane enzymes were abnormal. Some of these fetuses had echogenic masses in the abdomen demonstrated by ultrasonography at the time of amniocentesis (Fig 6). The high incidence of meconium ileus diagnosed by ultrasonography in these fetuses, much greater than the 10% to 15% incidence of meconium ileus in newborns, may be related to the inclusion of both
ET AL
true meconium ileus and transient ileal obstruction in some of these fetuses. Prenatal ultrasonographic findings of meconium peritonitis have been clearly described. Fetal ascites, sometimes loculated, is seen, and echogenic debris in the fluid may be shown.22*23 Calcifications surrounding the fluid may be demonstrated by the identification of intensely echogenic areas with posterior shadowing.24 An inhomogeneous mass, sometimes with echolucent and echogenic components, is often present (Fig 6). 24,25This mass of meconium may have an intensely echogenic rim with posterior enhancement, indicating calification of its border (Fig 7).26 Maternal hydramnios frequently accompanies these findings.‘*23x26 Most patients with CF who present with intestinal obstruction have meconium ileus. However, occasionally, the intestinal obstruction is incomplete and these children develop the meconium plug syndrome or small left colon syn-
GI MANIFESTATIONS
OF CYSTIC
Fig 3.
FIBROSIS
101
(COfl It’d).
drome. ‘h.27.28The meconium plug syndrome is most commonly seen in infants of diabetic mothersz9 or in babies with hypermagnesemia secondary to maternal intake of magnesium sulphate for toxemia.30 Hirschsprung’s disease and CF should also be included in the differential diagnosis. Meconium ileus equivalent, a term coined by Jensen in 1962,3’ refers to obstruction, frequently transient, in the distal small bowel by thick stool, in the older patient with CF.32 In part, it may be due to the absence of exogenous pancreatic enzymes. Therapeutic enemas with N-acetyl cysteine (Mucomyst [Mead Johnson Pharmaceutical, Evansville, IN]) or Gastrografin often relieve the obstruction. Radiographs of the abdomen reveal dilated loops of small bowel, often
with air-fluid levels and a bubbly soft tissue mass in the distal ileum and cecum. The inspissated stool may act as a lead point for intussusception.lh In children with CF, the appendix is sometimes enlarged and edematous and may also intussuscept (Fig 8). ASCITES
Ascites has been mentioned previously in the context of complicated meconium ileus. Ascites may also be secondary to hypoproteinemia from malabsorption.‘h Infants not suspected of having CF often have their formula changed when diarrhea develops. Soy bean formula, which is less allergenic than cow’s milk, is often used. This source of protein has been found to be poorly utilized by infants with CF, and has caused
102
ABRAMSON
Fig 4. Complicated meconium ileus with pseudocyst formation. IA) Supine and (B) lateral with a calcific rim. Note the dilated loops of small bowel and absence of gas in the rectum. atresia.
hypoproteinemia and anasarca. Human milk has a low protein content compared with cow’s milk, so that it too is more apt to lead to hypoproteinemia. CF should be considered in any infant who presents with edema and a normal urine analysis.33
OTHER BOWEL
CHANGES
In older children with CF, the duodenum and small bowel often appear abnormal. Particularly in the duodenum, the mucosal folds may appear thickened and nodular. This may be due to abnormally thick mucus produced by the mucous glands, hypertrophy of Brunner’s gland, or the
radiographs The child
reveal a large had associated
ET AL
mass ileal
increased effect of gastric acid without the normal buffering. Effacement of the duodenal loop may be caused by fatty replacement and distortion of the pancreas.34In older children and adults, the small bowel may be universally involved with markedly thickened and distorted mucosal folds, and mildly dilated loops that appear neither edematous nor separated. Some patients demonstrate severe involvement from the ligament of Treitz to the rectum (Fig 9).35336 Colonic pneumatosisis occasionally shown on abdominal radiographs in children with CF; it is seen at autopsy in 5% to 10% of cases. It is usually asymptomatic. Duodenal ulcer is seen at autopsy in 10% of
GI MANIFESTATIONS
Fig4.
OF CYSTIC
FIBROSIS
103
(‘Cent‘dl.
patients with CF. It is rarely diagnosed during life.‘6,34 HEPATOBILIARY
DISEASE
Hepatobiliary manifestations of CF vary. Neonatal jaundice may be the first sign. Abnormally thick bile may become inspissated in the biliary tree and lead to cholestasis.The diagnosis may be mistaken for biliary atresia. Technetium 99m-iminodiacetic acid (99”Tc-IDA) scanning after pretreatment with phenobarbitol may show no excretion into the GI tract, just as is seen in biliary atresia. In fact, such patients may be
explored for biliary atresia. In one such case, the gall bladder and extrahepatic ducts were found to be filled with abnormally tenacious bile. Once the biliary tract was cleared of this abnormal bile, an operative cholangiogram revealed a normal intrahepatic and extrahepatic biliary tree. A sweat test subsequently performed was abnormal. An enlarged fatty liver may be the presenting sign of CF. Fatty infiltration of the liver may be seenat various times in the course of CF, and is related to protein deficiency. Fat accumulates in the liver when the protein moiety of lipoprotein is
104
ABRAMSON
ET AL
Fig 5. Intact intestinal tract with evidence of meconium peritonitis. (A) Plain radiograph of the abdomen in a child referred for scrotal masses reveals a normal bowel gas pattern. Irregular calcifications in the right upper quadrant indicate previous bowel perforation with meconium peritonitis. (B) Film of the scrotum shows bilateral calcifications.
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
Fig 6. Prenatal sonographic diagnosis of cystic fibrosis with meconium ileus. (A) Longitudinal real time ultrasonogram reveals an irregular echogenic mass in the fetal abdomen (arrows). (B) Autopsy confirmation. Note the dilated loops of small bowel filled with meconium. Microcolon is present. (Courtesy of Dr A. Boue.“)
105
/ ’
Fig 8. lntussusception in CF. Barium enema on a 16year-old with CF who had complained of adbominal pain for e week shows a typical coilspring appearance with mess effect in the cecum. The appendix is seen within the mass. At surgery. the lead mass of the intussusception was the thickened and edematous appendix. The bowel was viable.
Fig 7. Prenatal sonographic diagnosis of meconium peritonitis. The fetal liver (I) is floating in ascitic fluid (a). An echogenic mess (lower arrowhead) is seen, with posterior shadowing. An echogenic rim is present about the abdominal wall (upper arrowhead). h, Fetal heed: p. placenta. IReprinted with permission of Dr David Rochester.“)
Fig 9. Bowel changes in CF. IA) Radiogr bowel the dluodenum and proximal small irregL alar thickening and nodularity o d the du folds. (Bt Delayed film shows distor ?ed and ened folds all through the small bov vel. The affected. colon was similarly
,aph of shows thickentire
Fig 10. Fatty infiltration of the liver in CF. (A) Longitudinal ultrasonogram of liver reveals an enlarged diffusely echogenic liver with poor through transmission. 16) Topogram of CT shows diffuse lucency in the liver, indicating fatty infiltration. (Cl CT of the upper abdomen after oral (but not IV) contrast medium reveals strikingly decreased density of the entire liver.
Fig 11. The gallbladder in CF. This ultrasonogram obtained after fasting shows a small irregular gall bladder (arrows) containing hypoechoic material.
Fig 12. Ultrasonogram reveals gall bladder sludge with posterior shadowing in a 4-month-old infant with malabsorption and abdominal distension. Sweat test was abnormal.
ABRAMSON
ET AL
Fig 13. Transverse ultrasonogram of the upper abdomen in an adolescent with CF. A small echogenic pancreas (outlined by crosses) is shown. S, superior mesenteric artery.
unavailable,3s and when there is depletion of proteinaceous liver enzymes concerned with fat metabolism.39 Fatty liver may occasionally be suspected on abdominal radiographs when lucency in the liver region is apparent.40*4’ More recently, fatty infiltration of the liver has been diagnosed by ultrasonography and CT (Fig 10). On sonography, increased echogenicity of the liver with decreased transmission of sound waves through it suggests fatty infiltration. On CT, fatty infiltration of the liver is clearly shown. The entire liver may reveal decreased density with bright portal venous areas.42 However, patchy fatty infiltration of the liver may also be recognized. Cyst-like changes represent the areas of fatty involvement surrounded by fibrosis.43 Other changes in the liver may be seen on ultrasonography. An enlarged liver or a small irregular liver may be identified in some patients. Irregular echogenicity may be scattered throughout the liver, sometimes in a nodular fashion, or may be most prominent in the periportal areas.44*45 When the liver is small and irregularly echogenic, especially in the periportal areas, biliary cirrhosis is suggested.
Splenomegaly may be seen on sonography. An enlarged splenic vein is sometimes present. These findings suggest portal hypertension. CT of the liver in children with CF may reveal a normal, small, or enlarged liver. Splenomegaly may be present and enlargement of the splenic and superior mesenteric veins may be seen. When a shrunken liver is present along with splenomegaly and visualization of the superior mesenteric and splenic veins, a diagnosis of biliary cirrhosis with portal hypertension is strongly suggested.42 Although this is seldom recognized clinically in CF, liver biopsy and autopsy studies indicate that up to 50% of patients with CF have focal biliary cirrhosis.42.45.46 On sonography, the gall bladder in CF may be normal or sma11.44 Sometimes a tiny shrunken gall bladder is almost indiscernible (Fig 11). Sludge or calculi in the gall bladder may be seen (Fig 12) ?5,47 True calculi may be difficult to identify in a shrunken gall bladder. The pancreas is abnormal in 75% of children under 5 years of age and 95% of children over 5 years of age with CF.45 It shows a variable ultrasonographic appearance (Fig 13). Most
GI MANIFESTATIONS
OF CYSTIC
FIBROSIS
Fig 14. Pancreatic cystosis in CF. (AI Longitudinal ultrasonogram area of the pancreas. (B) CT of the same patient shows a large cystic Hernanz-Schulman et alw and N.T. Griscom.)
111
of upper abdomen mass in the area
reveals of the
multiple pancreas.
large cysts in the (Courtesy Drs M.
112
ABRAMSON
commonly, it appears small and echogenic, 44345347x48 sometimes showing pancreatic calcifications. On CT, the pancreas is usually small and replaced by fat.42343349 Some patients with fatty infiltration of the pancreas have clinical diabetes.
ET AL
However, this association is inconstant.50~5’ Scattered cysts are sometimes seen, usually small and in the pancreatic tai1.48.49,52 Giant cystic replacement of the pancreas (pancreatic cystosis) has also been described on sonography and on CT (Fig 14).53
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GI MANIFESTATIONS
3X.
Lombardi
OF CYSTIC
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FIBROSIS
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