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1 All authors: Department of Radiology, Autonomous University of Barcelona, Hospital Universitari Germans Trias i Pujol, Carretera de Canyet s/n, Badalona E-08916, Spain.
Received March 25, 2003;
accepted after revision September 24, 2003.
Address correspondence to J. D. Casas
(jdcasas{at}ns.hugtip.scs.es).
Abstract
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MATERIALS AND METHODS. We conducted a retrospective review of 148 patients who underwent unenhanced and contrast-enhanced helical CT within 72 hr after onset of symptoms of a first episode of acute pancreatitis. Patients were classified by CT grade and grouped into two categories (mild: grades A, B, C; and severe: grades D and E) that were correlated with complications and death. In the grades including patients with pancreatic necrosis, it was also correlated with complications and death.
RESULTS. All complications (n = 15) and deaths (n = 4) occurred in patients with a CT grade of severe disease; differences as compared with mild grade were significant (p < 0.001 and p < 0.03, respectively). CT grade had a sensitivity and specificity of 100% and 61.6%, respectively, for predicting morbidity and 100% and 56.9% for predicting mortality. The 13 patients with necrosis were all in the severe group (p < 0.001). Necrosis detection on early CT had a sensitivity and specificity of 53.3% and 90.2%, respectively, for predicting morbidity and 75% and 83.8% for mortality.
CONCLUSION. Early unenhanced CT alone was a good indicator of severity of acute pancreatitis in our selected population. CT grade was sensitive for predicting outcome in acute pancreatitis. Pancreatic necrosis, estimated on early, contrast-enhanced CT and seen only in patients having severe disease, was a specific predictor of morbidity and mortality. These findings lead us to suggest that the use of iodinated contrast material to assess necrosis can be reserved for only those patients classified as having severe disease on unenhanced CT.
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In recent decades, several authors have indicated that CT can help in determining the prognosis of acute pancreatitis; the CT findings in these works correlated with clinical course, complications, and mortality in patients with acute pancreatitis [2–5]. These findings led to the development of the CT grade, a classification system that assesses the degree of pancreatic gland inflammation and extension to the extrapancreatic spaces [4].
Necrosis of the pancreas develops in 5–20% of patients with acute pancreatitis. This parameter is considered by some authors to be the most important for predicting morbidity and mortality because it has been related to duration of hospitalization, local complications, and mortality [6, 7]. For this reason, assessment of pancreatic necrosis has been added to the CT grade, resulting in the CT severity index [8]. Nevertheless, recent studies have questioned the importance of necrosis in estimating the prognosis of these patients. Some authors have found no correlation between pancreatic necrosis and clinical consequences such as local or systemic complications, duration of hospitalization, or mortality [9]. Others have found that the predictive value of the CT severity index is similar to that of the CT grade, suggesting that the addition of extent of necrosis to this scoring system does not contribute to the assessment of prognosis [10]. Furthermore, CT identification of pancreatic necrosis is achieved only through the use of iodinated contrast agents, the devitalized areas being detected by their lack of enhancement after the IV administration of a bolus [11–14]. However, the use of IV contrast material carries a risk of nephrotoxicity, particularly in patients with kidney failure [15], and there is some discussion as to the potential deleterious effect that vasoactive contrast material may have on the microcirculation of the inflamed pancreas [16, 17].
Controversy also exists regarding the moment during the course of acute pancreatitis at which CT should be performed. Most authors accept an initial CT study but establish widely varying intervals from the onset of symptoms to scanning that ranges from 48 hr to 10 days [1, 3, 7, 18]. Some authors recommend a CT study at 3–10 days after hospitalization for severe acute pancreatitis, contending that CT is difficult to interpret before 72 hr and that the areas of necrosis are better delimited after this time [1]. Nevertheless, because necrosis develops in the first 2–4 days after the onset of symptoms and rarely progresses [7, 18], it would be clearly advantageous to gain early knowledge of this factor by performing CT sooner to estimate the prognosis.
Thus, the best time and the best way to perform CT studies yielding optimum results for evaluating the severity of acute pancreatitis remain uncertain. The aim of this study was to determine whether early helical CT is effective in assessing the prognosis of acute pancreatitis, to evaluate the contribution of pancreatic necrosis as a prognostic marker, and to determine whether the routine IV administration of iodinated contrast material is necessary when using early CT for grading acute pancreatitis.
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Acute pancreatitis was due to gallstones in 84 patients (57%), to alcohol overindulgence in 31 (21%), and to both causes in seven (5%). The cause was idiopathic in 20 patients (14%) and miscellaneous in six patients (4%): two ampullary carcinomas, pharmacologic acute pancreatitis in two HIV patients treated with didanosine and lamivudine, one sclerosing cholangitis, and one ERCP-induced acute pancreatitis. An appropriate institutional review board approved the study.
Imaging Technique
Scanning was performed at 120 kV and 250 mAs on a helical scanner (PQ 5000,
Picker International, Highland Heights, OH). Half an hour before data
acquisition, 250–500 mL of oral contrast material was administered for
bowel opacification. CT images were obtained in a craniocaudal direction.
First, an unenhanced CT study of the abdomen was performed with 10-mm slice
collimation, a pitch of 1.5, and a 10-mm reconstruction interval, to determine
the extent of extrapancreatic inflammation and the exact position of the
pancreatic gland. Through an 18- to 20-gauge IV cannula placed in an
antecubital fossa vein, 100 mL of nonionic contrast material (370 mg I/mL) was
administered with an automated power injector at a rate of 3 mL/sec. Starting
70 sec after initiation of the monophasic IV injection, contrast-enhanced CT
of the pancreas alone was performed with 8-mm slice collimation, a pitch of
1.5, and a 5-mm reconstruction interval.
Data Analysis
Consensus interpretation and scoring of the unenhanced CT images were
performed by two of the authors using the CT grade: grade A, normal pancreas;
grade B, focal or diffuse pancreatic enlargement; grade C, inflammation of
pancreas or peripancreatic fat or both (Figs.
1A and
1B); grade D, single
peripancreatic fluid collection; and grade E, two or more fluid collections or
retroperitoneal air [4]
(Fig. 2A). The reviewers also
determined the absence (Fig.
1A,
1B,
1C,
1D) or the presence (Figs.
2A,
2B,
2C and
3A,
3B,
3C) of pancreatic necrosis,
defined as a lack of enhancement in the gland after IV contrast injection. The
clinical course of each patient from hospital admission to discharge was
reviewed, and data were collected on the appearance of acute
pancreatitis–related complications (abscesses, pseudocysts, multiorgan
failure, and sepsis) and whether death occurred. To facilitate interpretation
of the results, the CT grading categories were grouped into mild (A, B, and C)
and severe (D and E) and were correlated with the development of complications
and death. To study the prognostic value of pancreatic necrosis, we combined
the CT grades of patients with necrosis, and in this subgroup the presence or
absence of necrosis was also correlated with complications and mortality.
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The data obtained were entered in the Access database (Microsoft Iberica, Barcelona, Spain) and later imported to the SAS statistics package (SAS Institute, Cary, NC) for analysis. The mean and the intervals were used in the description of numeric values, and the percentage corresponding to each category was calculated for categoric values. Bivariate relations were assessed by calculating the odds ratios and their 95% confidence intervals (CIs) and by using the chisquare analysis or Fisher's exact test when appropriate, depending on the sample size.
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CT Grading
Using the early unenhanced CT study, we classified 82 patients (55%) as
having mild acute pancreatitis (grade A, 38 patients [25.7%]; grade B, 20
patients [13.5%]; grade C, 24 patients [16.2%]) and 66 (45%) as having severe
acute pancreatitis (grade D, 27 patients [18.2%]; grade E, 39 patients
[26.4%]). Tables 1 and
2 show the relationship between
CT grade and morbidity and mortality as determined in our series. All
complications and deaths occurred in the severe group, mainly in the patients
with grade E disease, with statistically significant differences for both
morbidity (p < 0.001) and mortality (p < 0.03) as
compared with patients with mild disease. The sensitivity and specificity of
CT grade for predicting complications were 100% (15/15) and 61.7% (82/133),
respectively; and the sensitivity and specificity for predicting mortality
were 100% (4/4) and 56.9% (82/144), respectively.
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Pancreatic Necrosis
The presence of necrosis was identified on early contrast-enhanced CT in 13
(8.8%) of the 148 patients. Necrosis was significantly present (p
< 0.001) in patients with a severe CT grade (two patients having grade D
and 11 having grade E), so we focused on this subgroup to study the relation
between this factor and the development of complications or death.
The value of pancreatic necrosis as a predictor of complications was assessed in the 66 patients with a CT grade of severe (Table 3). Results showed that 13.2% of patients without necrosis as compared to 61.5% of patients with necrosis developed complications (p < 0.001). Five patients with necrosis on the initial CT study had a favorable clinical course. Two of these patients were grade D and the other three, grade E; in all five, necrosis affected less than 30% of the pancreatic gland. In patients with a CT grade of severe, the odds of developing a complication were 10 times higher (95% CI, 2.7–41.4 times) when necrosis was present on early CT studies than when it was not. Thus, in this group of patients, the sensitivity and specificity of early CT detection of necrosis for predicting complications were 53.3% (8/15) and 90.2% (46/51), respectively.
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We also analyzed the value of presence of necrosis as a predictor of mortality in patients having a CT grade of severe (Table 4). Three deaths occurred among the 13 patients with necrosis on early CT, as compared with only one death (a patient with grade E disease) among the 53 patients without necrosis (p < 0.02). The odds that death would occur were 15 times higher (95% CI, 1.5–165.6 times) in the patients with necrosis than in those without. Finally, the sensitivity and specificity of necrosis for predicting death in the group of patients having a CT grade of severe were 75% (3/4) and 83.9% (52/62), respectively.
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This study may have some bias because the criteria for inclusion were quite strict and restrictive; among the initial group of 375 patients diagnosed with acute pancreatitis in our center during the study period, 227 (60.53%) were excluded. The exclusion criteria were established with the aim of forming a homogeneous group in whom contrast-enhanced helical CT was performed following a single protocol and always within 72 hr after onset of symptoms. Therefore, it was necessary to exclude a large number of patients with severe acute pancreatitis who were first cared for in other hospitals in our public health region and later transferred to our referral center because of an unfavorable clinical course. In many of these patients, CT had not been performed or had been performed according to a different protocol than that applied in our center. Exclusion of these patients explains why our study has a lower percentage of severe acute pancreatitis cases than other series [8]. In any case, although the study criteria required the exclusion of many patients, the course of those patients probably would not have been different from the course of those included as long as CT grade and degree of pancreatic necrosis were similar.
The percentage of patients with necrosis in our sample (8.8%) was within the range (5–20%) described in the literature [7, 12, 14] and was found only in patients having a CT grade of severe. Pancreatic necrosis was a good predictor of morbidity and mortality in this group, showing high specificity: when necrosis was detected on early initial CT, the odds of developing complications or of dying were 10 and 15 times higher, respectively, than when necrosis was not present. Other authors reported that necrosis was a good indicator of future complications, but mortality was found to be similar in patients with, and in those without, necrosis [8]. Nevertheless, even considering pancreatic necrosis to be the primary cause of morbidity and mortality in acute pancreatitis, one should not overlook the fact that patients with a CT grade of severe (D or E) and no pancreatic necrosis can also be at risk; these patients presented 13.2% of the complications in our series and 22% in a study by other authors [8]. Necrosis of retroperitoneal fat, which can undergo liquefaction and become infected, may be partially responsible for the development of local complications in this subset of patients. A significant shortcoming of current imaging techniques is their inability to differentiate between fluid collections and necrosis of extrapancreatic fatty tissue.
Pancreatic necrosis seems to have developed early among the patients studied. None of the patients with a CT grade of mild had a poor outcome, and none of the few patients who underwent follow-up CT showed late-developing necrosis. These results are in keeping with the idea that necrosis almost always occurs within 48 hr after the onset of symptoms [7, 18], with late necrosis being infrequent (< 5%) and always occurring in patients with a CT grade of severe (D or E), who were initially included in the group with an unfavorable prognosis [8]. Therefore, CT findings obtained within 72 hr after symptom onset are valid for establishing an early prognosis of acute pancreatitis; a delay in performing the initial study is not required.
Glandular necrosis is an important feature for determining prognosis and guiding treatment in patients with acute pancreatitis, so many authors advocate the use of contrast-enhanced sequences in all patients in whom CT is indicated. Nevertheless, careful assessment of results from the unenhanced CT studies in these patients and their implications for grading the disease and estimating prognosis provides a different focus on this issue from the viewpoint of clinical practice. In our study and in others [3, 4], classification of patients with acute pancreatitis according to the CT grade, which does not require iodinated contrast material, proved to be sensitive for determining prognosis. In fact, in one study the predictive values of the CT grade were identical to those of the CT severity index, which does require contrast material [10]. Most important, in our opinion, is the fact that necrosis was not detected in any patient with mild acute pancreatitis (82/148 patients) defined in this study using the CT grade, and this observation seems to be supported by the literature. In the single series in which the presence of necrosis was specified in each CT grade, very few (3.41%) mild cases had necrosis, and these patients were later seen to have no complications [8]. These data seem to indicate that the routine use of contrast material is not necessary in all patients who have disease classified as mild by CT grade.
To summarize, this retrospective review of early CT in acute pancreatitis sheds some light on the questions of when and how to perform studies that will yield useful information for patient management, with attention to the invasiveness of the technique. Early examinations carried out within 72 hr after the onset of symptoms were accurate without the use of IV contrast material for classifying disease as mild or severe. This fact, the absence of necrosis, and a favorable clinical course in all patients having mild disease lead us to suggest that contrast-enhanced sequences should be added to the CT study only in patients classified on unenhanced CT as having severe disease (grades D and E). In that subgroup, classification of the severity of acute pancreatitis by grade on unenhanced sequences and investigation of pancreatic necrosis on contrast-enhanced sequences increase the specificity of early CT estimation of prognosis.
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