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Gastrointestinal Imaging |
1 Department of Body and Vascular Imaging, Hôpital Lariboisière-AP-HP, 2 rue Ambroise Paré, 75475 Paris 10, France (P.S., J.P.P., R.R.)
2 Laboratoire de Radiologie Expérimentale et de Pathologie Articulaire, Faculté de Médecine Lariboisière–Saint Louis Université Paris VII, France (P.S.)
3 Department of Radiology, Hôpital Foch, Suresnes, France (L.S., A.C.D., Y.R., M.G., A.S.).
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Abstract |
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MATERIALS AND METHODS: CT scans in 15 patients with CF (group 1) and in 15 control subjects without CF (group 2) were evaluated for thickness and degree of pancreatic fatty replacement. Thickness was measured at four anatomic levels. The pattern of pancreatic fatty replacement was visually evaluated in four pancreatic regions. Images were semiquantitatively analyzed by two readers. The degree of fatty replacement was correlated with the functional status of the pancreas.
RESULTS: In group 1, pancreatic glandular tissue was significantly thinner (P < .001) and the degree of fatty replacement was significantly greater in the four regions (P < .001) than those in group 2. In Group 1, no relationship was found between the degree of pancreatic fatty replacement and that of pancreatic endocrine dysfunction. A significant relationship was found between the degree of fatty replacement and that of pancreatic exocrine dysfunction (P < .001).
CONCLUSION: In patients with CF, pancreatic glandular tissue is significantly reduced in size. Pancreatic fatty replacement is the most frequent pattern in older patients with CF and correlates with pancreatic exocrine dysfunction.
Index terms: Fibrosis, cystic, 77.1496 • Pancreas, CT, 77.12111, 77.12112 • Pancreas, fat, 77.929 • Pancreas, function, 77.91
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Introduction |
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Although the course and prognosis of CF are mainly determined by the progression of pulmonary obstruction and infection, assessment of pancreatic damage may be of clinical relevance in screening for patients at high risk for early development of pulmonary infection (3). It has been reported (3) that patients with pancreatic insufficiency actually may have earlier colonization of the airway by Pseudomonas aeruginosa, an event that is believed to be the turning point in the clinical development of CF.
A few investigators (4–8) have attempted to assess the usefulness of imaging in the evaluation of involvement of abdominal organs by CF. Pancreatic changes have been described at ultrasonography (US) (4,5), computed tomography (CT) (5,6), and magnetic resonance (MR) imaging (6–8). However, we are aware of only two studies (6,8) in which imaging findings were correlated with patients' pancreatic status. In both studies, MR imaging was used; so, to our knowledge, there is no study in which the degree of fatty replacement as seen at CT was correlated with the functional status of the pancreas.
The goal of this study was to compare the CT features of pancreatic fatty replacement in older patients (adolescents and adults) with CF with those of control subjects with neither CF nor pancreatic disease and to correlate the degree of fatty replacement with the functional status of the pancreas.
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MATERIALS AND METHODS |
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F508 deletion, four (27%) were heterozygous for the F508 deletion, and three (20%) had another CF mutation. All patients were evaluated for pancreatic insufficiency according to their clinical status (ie, steatorrhea), the results of fatty residual analysis in stool, and the dosage of enzymatic substitutive therapy (pancrelipase). Eleven patients had increased fecal fat excretion (range, 26–64 g per 24 hours) and were treated with pancrelipase; on the basis of the value of fecal fat excretion, six of these patients had moderately increased fecal fat excretion, and five patients had markedly increased fecal fat excretion. Four patients did not have steatorrhea at repeated tests. Three patients with increased fecal fat excretion also had type 1 diabetes mellitus, which required treatment with insulin.
Fifteen age- and sex-matched patients (nine male and six female patients) with a mean age of 27 years ± 8.3 (range, 17–38 years) without CF (group 2) served as control subjects. These patients with neither CF nor pancreatic disease were selected retrospectively from a population of patients who underwent CT of the upper abdomen. They were not obese (body mass index < 25 kg/m2) and were not taking any glucocorticoids or thiazides. They were scheduled to undergo abdominal CT as part of a medical work-up for evaluation of unexplained abdominal pain. Results of CT and follow-up evaluation excluded pancreatic disease in all patients in this group. CT of the pancreas was performed with the same parameters as those used in the patients with CF. The selection criteria for the control subjects were no diagnosis of CF and no known diagnosis of pancreatic disease.
All patients with CF and control subjects underwent CT examination of the abdomen according to the routine protocol of our department. An Elite Plus scanner (Elscint, Haifa, Israel) was used, with 10-mm collimation at an interval of 10 mm. In addition, the pancreas was studied with 5-mm-thick contiguous sections. CT scans were obtained without and with contrast material enhancement in all patients. Patients received 100–120 mL of nonionic iodinated contrast material (iobitridol, Xenetix; Laboratoires Guerbet, Roissy, France), which contained 300 mg of iodine per milliliter. The contrast material was administered with a mechanical power injector at a rate of 1.2 mL/sec into an antecubital vein through an 18- or 20-gauge cannula, with a delay of 25 seconds. Oral contrast material was administered to all but three patients. These three patients, two with CF, did not receive oral contrast material because they were suspected of having a biliary stone.
CT images were evaluated by two radiologists (P.S., L.S.) who were unaware of the clinical and biologic status of the patients. The images of the patients with CF and of the control subjects were gathered together and subsequently evaluated in a random fashion by the two radiologists, who performed the readings side by side to obtain a consensus.
All CT images were evaluated for pancreatic abnormalities by assessing the thickness of the pancreatic glandular tissue and the morphology of the pancreas. Thickness of the pancreatic glandular tissue was measured at four pancreatic regions (head, neck, body, and tail), and sizes were noted in millimeters. Thickness was measured on the right side of the superior mesenteric vein for the head, at the level of the superior mesenteric artery for the neck, in the extension of a line drawn from the left border of the vertebral body for the body, and from the internal border of the left kidney for the tail (9). Measurements were made by one radiologist (P.S.), who worked at a commercially available independent display console (IDC Exel Line; Elscint) and used electronic calipers. Measurements involved the glandular tissue of the pancreas (on the basis of its soft-tissue attenuation) and, when present, excluded the fatty tissues.
The morphology of the pancreas was qualitatively evaluated and categorized into four patterns: normal pancreas, atrophy of the pancreas without fatty replacement, partial fatty replacement of the pancreas, and subtotal or complete replacement of the pancreas by hypertrophic fatty tissue. The pattern of pancreatic fatty replacement was further visually evaluated at four pancreatic regions (head, neck, body, and tail). Images were semiquantitatively analyzed by two readers (P.S., L.S.) who used a five-point scale: Grade 0 corresponded to a normal appearance of a given pancreatic region, without fatty replacement (Fig 1); grade 1 corresponded to fatty replacement that involved less than 25% of a given pancreatic region; grade 2 corresponded to fatty replacement that involved 25%–50% of a given pancreatic region (Fig 2); grade 3 corresponded to fatty replacement that involved 50%–75% of a given pancreatic region; and grade 4 corresponded to fatty replacement that involved more than 75% of a given pancreatic region (Fig 3). The degree of fatty replacement of the pancreas was correlated with the functional status of the pancreas.
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2 test; the Yates correction for small samples was applied when needed. A P value of less than .05 was considered to indicate a statistically significant difference. |
RESULTS |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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F508 deletion (Fig 1). This patient had azoospermia at the time of presentation, with neither lung disease nor pancreatic insufficiency.
In group 1, partial fatty replacement of the pancreas was found in eight (53%) patients; of these, one patient had moderately increased fecal fat excretion and type 1 diabetes mellitus, four patients had moderately increased fecal fat excretion only (Fig 2), and three patients had normal pancreatic function. Of the eight patients with partial fatty replacement of the pancreas, three patients were homozygous for the F508 deletion, three patients were heterozygous for the F508 deletion, and two patients had another CF mutation.
In group 1, subtotal or complete replacement of the pancreas by hypertrophic fatty tissue was found in six (40%) patients; of these, two patients had markedly increased fecal fat excretion and type 1 diabetes mellitus (Fig 3), three patients had markedly increased fecal fat excretion only, and one patient had moderately increased fecal fat excretion only. Of the six patients with subtotal or complete fatty replacement of the pancreas, five patients were homozygous for the F508 deletion, and one patient had another CF mutation. All patients with markedly increased fecal fat excretion were homozygous for the F508 deletion, with the result of a statistically significant relationship between degree of pancreatic exocrine insufficiency and genotype (P < .05). In group 1, no such relationship was found between the degree of pancreatic fatty replacement and that of pancreatic endocrine dysfunction. In group 1, a significant relationship was found between the degree of fatty replacement of the pancreas and that of pancreatic exocrine dysfunction (P < .001; 2 test).
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DISCUSSION |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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During a review of autopsy findings in 27 patients with CF who died at their institution during 5 years, Daneman et al (5) found diffuse fatty replacement of the pancreas in 15 (56%) patients and minimal or no fat replacement in 12 (44%). The mean ages in these two groups were 17 years and 11 years. In our study with adolescent and adult patients only, all but one patient with CF had diffuse fatty replacement of the pancreas, and our results are in accordance with those of Daneman et al.
The pathologic alterations of the pancreas in patients with CF were responsible for the initial identification and naming of the disease (CF of the pancreas) (11). At all ages, however, there is a spectrum of anatomic changes in the pancreas of patients with CF (2,10). Besides lipomatous involution, other pancreatic changes can be present in patients with CF. In the subset of patients with CF who do not have impaired exocrine pancreatic function, only minimal pathologic lesions are found. Conversely, patients with severe, long-standing symptoms of malabsorption may show marked fibrosis, fatty replacement, and cysts in the pancreas. Hernanz-Schulman et al (12) and Tjon A Tham et al (6) reported multiple microscopic or small macroscopic cysts in the pancreas. These are true cysts, lined by epithelium, which are thought to be secondary to inspissated secretions (2,10–12). Sometimes, stone formation or calcification within the ducts and body of the pancreas occurs (13). We observed no cases of pancreatic cystosis or pancreatic calcifications in our study.
The role of the different imaging techniques in the assessment of pancreatic involvement during the course of CF has previously been addressed (4–7). US cannot be used to depict subtle changes in pancreatic morphology (4). When the pancreas is seen, it has increased echogenicity due to fatty replacement of the exocrine part (14). Although CT has the major disadvantage of the use of ionizing radiation (5), it accurately demonstrates the various pancreatic changes that can be present in patients with CF. An advantage of MR imaging is the combination of an accurate assessment of fatty replacement of the pancreas with the lack of ionizing radiation. In addition, a good correlation has been reported (6) between CT and MR imaging findings. In addition, as suggested by Ferrozzi et al (8), MR imaging may offer another advantage as compared with CT, because the former demonstrates subtle variations in the morphologic appearance of the pancreas in patients with CF; these variations may not be seen at US and CT.
In our study, we observed a uniform fatty replacement of the pancreas in 14 (93%) of 15 patients with CF. We found that the four regions of the pancreas were equally affected and that the process is diffuse in nature. Conversely, in obese patients, an uneven fatty replacement of the pancreas usually is observed, which more severely involves the anterior aspect of the head of the pancreas (15). Fatty replacement with atrophy of the pancreas can also be due to Cushing syndrome, steroid therapy, major malnutrition, main pancreatic duct obstruction, Shwachman syndrome, hemochromatosis, or viral infection (16,17). In histologic terms, fibrofatty replacement of the acini with preservation of islet cells are observed in all these diseases; such changes are similar to those observed experimentally after ligature of the main pancreatic duct (16,17). Fatty replacement of the pancreas in CF is thought to be due to the same mechanism and to result from protein plug obstruction of the acinar duct (6).
There is a spectrum of severity of the clinical findings in patients with CF at all ages (2,10). The majority of adult patients with CF have biochemical evidence of exocrine pancreatic insufficiency, and more than 80% of them do not release enough pancreatic enzymes into the gastrointestinal tract to support normal digestion of nutrients (18). The presence of steatorrhea in patients with CF correlates with a pancreatic enzyme output that is less than 10% of the normal value. These patients are considered to be "pancreatic insufficient" (19). In 10%–15% of CF patients who have less pronounced pancreatic involvement, there is a sufficient amount of functional pancreatic exocrine tissue to allow normal fat and protein digestion; the term "pancreatic sufficient" is used to describe these patients (19). It has previously been shown (20) that exocrine pancreatic insufficiency occurs only when more than 98%–99% of the entire pancreas is damaged. In our study, we observed patients with CF who had exocrine pancreatic insufficiency with less than 98%–99% of pancreatic involvement as seen on CT scans.
Patients with CF and severe pancreatic insufficiency commonly have more severe forms of lung disease and higher sweat chloride concentrations than do those with better pancreatic enzyme production (3). Disease of the pancreas is directly correlated with the genetic abnormality for CF, such that virtually all patients who are homozygous for the F508 deletion have pancreatic insufficiency, whereas patients with other mutations are considerably more likely to retain their pancreatic function (18). In our study, all 15 (100%) patients with markedly increased fecal fat excretion were homozygous for the F508 deletion, whereas seven (70%) of 10 patients with moderately increased or normal fecal fat excretion were heterozygous for the F508 deletion or had another mutation. Although this result was based on a small number of patients, it indicates a significant correlation between the degree of pancreatic insufficiency and genotype. Our result is in line with that of a previous study (3) in which patients with CF with the F508 genotype were shown to have a higher frequency of pancreatic insufficiency and earlier chronic airway colonization, which as previously stated, is strongly believed to represent the turning point in the clinical course of this disease.
In our study, we found that patients with CF had a significantly thinner pancreas than did control subjects. Apparently, this result differs from that of a previous study by Van Haren et al (21), who used US for pancreatic measurement. Van Haren et al found a significantly enlarged hyperechoic pancreatic head in patients with CF as compared with that in control subjects. This was due to the fact that pancreatic measurements in the study by Van Haren et al involved the whole pancreatic area that was subjected to fatty replacement instead of the remaining nonfatty pancreatic glandular tissue, which more accurately reflects the volume of functional pancreatic tissue.
Although we agree that our measurements of pancreatic size do not reflect the actual size of the entire pancreas, we believe that CT offers a more precise evaluation of the remaining pancreatic tissue in CF, as compared with US, because CT definitely demonstrates the glandular tissue within the pancreatic area. The quantification of fatty replacement of the pancreas is based on the ratio between the actual size of the remaining pancreatic glandular tissue and the estimated amount of fat present in the pancreas and the peripancreatic area. On CT scans in patients with CF, it may be difficult to distinguish between the actual intrapancreatic fat and the peripancreatic fat. This may explain why, in patients with CF, reduction in pancreatic glandular tissue does not correlate with increased fatty replacement.
As already stated, the degree of fatty replacement and atrophy as seen on MR images correlates with the severity of the expression of CF (6,8). A statistically significant reduction in T1 was noted in the patients with CF as compared with T1 in the control subjects (6,8). In addition, a statistically significant correlation between T1 shortening and pulmonary clinical-radiologic compromise and pancreatic insufficiency was found (8). MR imaging may offer further indications of pancreatic and, indirectly, pulmonary damage during the clinical course of CF. Further studies must be performed to determine if there is a correlation between the degree of fatty replacement of the pancreas as seen at CT and the Shwachman and Kulckzycki (22) lung score.
In conclusion, our results show that the pancreas is significantly reduced in size in patients with CF. Pancreatic fatty replacement is the most frequent CT pattern in adolescents and adults with CF; in addition, our results show a statistically significant correlation between the degree of fatty infiltration of the pancreas and pancreatic exocrine dysfunction.
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Footnotes |
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Abbreviation: CF = cystic fibrosis
Author contributions: Guarantor of integrity of entire study, P.S.; study concepts and design, P.S., A.S.; definition of intellectual content, P.S., L.S.; literature research, L.S., A.C.D.; clinical studies, Y.R., M.G., P.S., L.S., A.S.; data acquisition, M.G., P.S., L.S., Y.R., A.C.D.; data analysis, P.S., L.S.; statistical analysis, P.S., L.S.; manuscript preparation, P.S., L.S.; manuscript editing, P.S., J.P.P., R.R.; manuscript review, P.S., J.P.P., R.R., A.S.
Received June 17, 1998;
revision requested July 28, 1998; revision received August 20, 1998;
accepted October 7, 1998.
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References |
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TOPAbstractIntroductionMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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