Transcript A Comparative Evaluation of Radiologic and Clinical

A C OMPARATIVE E VALUATION OF
R ADIOLOGIC AND C LINICAL
S CORING S YSTEMS IN THE E ARLY
P REDICTION OF S EVERITY IN
A CUTE PANCREATITIS
INTRODUCTION

AP can vary from a mild self-limited disease in
approximately 80 – 90 % of patients, to a clinically severe
form in 10 – 20 % with local and systemic complications.

The identification of patients with clinically severe AP is
important for several reasons: first, these patients may
benefit from transfer to an intermediate or intensive
care unit, where they can receive aggressive fluid
resuscitation and be closely monitored for the
development of organ failure.

Second, these patients may benefit from targeted
therapy, i.e., enteral feeding, endoscopic
sphincterotomy, or antibiotics.

Finally, severity stratification is important when reporting
and evaluating the results of clinical trials in AP.

Besides assessment of relevant clinical and biochemical
parameters in AP, in many centers, it is standard practice to
obtain a computed tomography (CT) scan on admission (i.e.,
within 24 h of hospitalization), not only for diagnostic
purposes but also for assessing the severity of disease.

The severity of AP by CT imaging can be evaluated using
unenhanced or contrast-enhanced CT studies. Unenhanced
CT scoring systems evaluate the extent of pancreatic and
peripancreatic inflammatory changes (Balthazar grade and ‘‘
pancreatic size index ’’ or PSI) or evaluate both
peripancreatic inflammatory changes and extrapancreatic
complications ( ‘‘ mesenteric oedema and peritoneal fluid ’’
or MOP score, ‘‘extrapancreatic ’’ or EP score, and the more
recently developed ‘ ‘ extrapancreatic inflammation on CT ’ ’
or EPIC score).

In addition, there are two CT scoring systems that require
the use of intravenous contrast agents to determine the
presence and extent of pancreatic parenchymal necrosis.
The ‘ ‘ CT severity index ’ ’ or CTSI is a numerical scoring
system combining the quantification of extrapancreatic
inflammation with the extent of pancreatic necrosis.

Mortele et al. proposed a ‘‘ modified CTSI ’’ or MCTSI,
which, in addition to the CTSI, assigns points for
extrapancreatic complications (vascular, gastrointestinal
and extrapancreatic parenchymal complications as well as
the presence of pleural effusion and / or ascites).

Although many studies have demonstrated a correlation
between morphologic severity according to CT scoring
systems and clinical disease severity, only five utilized data
from “ early ” CT scans, defined as those obtained within
24 h of admission to the hospital.

No comparison of the accuracy of the existing CT scoring
systems was performed and no comparative assessment
was done between the CT scoring systems and clinical
scoring systems such as the (APACHE)-II and the recently
developed and validated Bedside Index for Severity in AP
(BISAP).

Th e aim of this study is to compare the accuracy
of seven different existing CT scoring systems in
predicting the severity of AP on the first day of
admission.

The secondary aim is to assess whether these CT
scoring systems are superior to two commonly
employed clinical scoring systems.
METHODS
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The demographic, clinical, and laboratory data of all
consecutive patients with a primary diagnosis of AP
admitted or transferred to our institution during a 2.5-year
period was prospectively collected for this study.

AP was defined as two or more of the following:
characteristic abdominal pain; serum amylase and / or
lipase levels three or more times the upper limit of normal
(i.e., >210 and 180 U / l, respectively); and / or an imaging
study (CT or magnetic resonance imaging) demonstrating
changes consistent with AP.

The day of admission was defined as the first 24 h of
hospitalization in our institution or in the referring hospital.

For all episodes, appropriate clinical data were recorded
prospectively by two authors (V.K.S. and K.R.), who were
unaware of the CT scores, to permit calculation of the
APACHE-II, BISAP, and Charlson Comorbidity Index scores.
The decision to obtain a CT scan was based on the clinical
discretion of the evaluating physician.

Two radiologists retrospectively reviewed all CT studies
and were unaware of patient outcomes.
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The following parameters were collected for each episode
of AP:
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In-hospital mortality, length of hospital stay, admission to
and length of intensive care unit stay, presence and
duration of organ failure (transient; ≤ 48 h and persistent;
>48 h), pancreatic infection (infection of pancreatic and /
or peripancreatic necrosis), and need for intervention
(endoscopic, percutaneous drainage, and / or surgical
necrosectomy).

Clinically severe AP was defined as one or more of the
following: mortality, persistent organ failure and / or the
presence of local pancreatic complications that require
intervention (endoscopic or radiologic drainage or surgical
necrosectomy).
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This definition is in accordance with the most updated
revised Atlanta classification.
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The principle distinction between the new and former
definition of clinical severity is that the mere presence of
pancreatic parenchymal necrosis, peripancreatic
collections, or organ failure is not regarded as clinically
severe disease, unless organ failure exceeds 48 h in
duration or complications of pancreatic necrosis or
peripancreatic collections occur, which require active
intervention.
S TATISTICAL ANALYSIS

Descriptive statistics were used for baseline
characteristics, outcomes, and CT parameters.

The diagnostic accuracy of each scoring system for
mortality and clinical severity were assessed using the
area under the receiver operating characteristic curve
(AUC) with standard error and 95 % confi dence intervals
(CIs).

To rule out potential bias introduced by the inclusion of
transferred patients, receiver operating characteristic
curve (ROC) analysis was also performed in the nontransferred group. All statistical analysis was performed
using SAS v.9.1 (SAS, Cary, NC), SPSS v15.0 (SPSS, Chicago,
IL), and MedCalc v.10.4.3.0 (MedCalc, Mariakerke,
Belgium).
RESULTS
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The 159 episodes of AP in which an early CT scan was
performed constitute our study cohort.
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The additional 187 episodes in which no ( n = 139) or
delayed ( n = 48) CT imaging was performed, were
excluded from the study.
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In 131 episodes, a contrast-enhanced CT was performed
permitting the assessment of all seven CT scoring systems;
Balthazar grade, CTSI, MCTSI, EP score, EPIC score, MOP
score, and PSI.

In 28 episodes, only an unenhanced CT scan was
performed, allowing the assessment of only fi ve of the
seven CT scoring systems.

The median age of patients was 54 years (range 21 – 91)
with 84 men and 66 women.

Etiologies of AP included gallstones in 4 8 (30 % )
episodes, miscellaneous (e.g., hypertriglyceridemia,
hereditary, and post-endoscopic retrograde
cholangiopancreatography) in 38 (24 % ) episodes, alcohol
in 34 (21 % ) episodes, idiopathic in 27 (17 % ) episodes,
and drug-induced in 12 (8 % ) episodes.
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One hundred and thirty episodes (82 % ) were labeled as
mild AP and 29 episodes (18 % ) as clinically severe AP.
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In 16 episodes, the lack of enhancement of pancreatic
parenchyma was noted indicating acute necrotizing
pancreatitis (four of whom were categorized as having
clinically mild disease).
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On follow-up imaging, 13 more episodes were identified,
in whom necrotizing pancreatitis was detected (three of
them had an unenhanced CT on admission). The lack of
enhancement on follow-up imaging was not used for data
analysis.

In all episodes, early CT did not reveal an alternative
diagnosis or local complication that changed clinical
management.
C OMPARISON OF SCORING INDICES IN
PREDICTING CLINICAL SEVERITY

On the basis of highest sensitivity and specificity values
generated from the ROC curves, the following cutoffs
were selected for predicting clinically severe disease:
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CTSI ≥ 4, MCTSI ≥ 6, Balthazar grade ≥ 5, EPIC score ≥ 3, EP
score ≥ 3, MOP score ≥ 2, PSI ≥ 1, APACHE-II ≥ 10, and
BISAP ≥ 3.
AUC comparison of computed tomography
(CT) and clinical scoring systems for
predicting clinical severity.

Although the CTSI demonstrated the highest accuracy for predicting
clinically severe AP among the 131 cases who underwent contrastenhanced CT (AUC 0.88; 95 % CI: 0.82 – 0.93), no statistically
significant pairwise differences were observed between the CTSI
and the other CT scoring systems, except for PSI ( P = 0.014).

Balthazar grade demonstrated the highest accuracy for clinically
severe AP for all 159 episodes (AUC 0.79; 95 % CI: 0.72 – 0.85).
However, no statistically significant differences were observed
between the Balthazar grade and the other CT scoring systems.
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Also, no statistically significant differences were found between the
CT and clinical scoring systems with highest AUC for clinical severity.
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No significant changes in results were observed when excluding the
transferred patients.
C OMPARISON
OF SCORING INDICES
IN PREDICTING MORTALITY

On the basis of highest sensitivity and specificity values
generated from the ROC curves, the following cutoffs
were selected for predicting mortality: CTSI ≥ 4, MCTSI ≥
4, Balthazar grade ≥ 5, EPIC score ≥ 3, EP score ≥ 3, MOP
score ≥ 1, PSI ≥ 1, APACHE-II ≥ 17, and BISAP ≥ 3.

Among the CT indices, Balthazar grade had the highest
AUC for mortality in both groups (AUC 0.81; 95 % CI: 0.74
– 0.88 and AUC 0.79; 95 % CI: 0.72 – 0.85, respectively).

In the study cohort, the APACHE-II score performed best
among all studied indices in both groups of patients (AUC
0.91; 95 % CI: 0.85 – 0.95 and AUC 0.91; 95 % CI: 0.86 –
0.95, respectively).
C OMPARISON
OF SCORING INDICES
IN PREDICTING MORTALITY

No statistically significant differences were observed
between Balthazar grade and the other CT scoring systems
and between Balthazar grade and the clinical scoring system
with the highest accuracy for predicting mortality (APACHEII).

When using a fixed cutoff value for APACHE-II for predicting
clinically severe disease and mortality (i.e., the universally
accepted value of 8 or more) there was an increase of the
sensitivity and negative predictive value and concomitant
decrease in specificity and positive predictive value
compared with the optimal cutoff s derived from the ROC
curves.

The AUC value of APACHE-II for both cutoff values was the
same and, again, no significant changes were seen between
CT scoring system and APACHE-II.
DISCUSSION

This study did not detect any significant differences
between the studied CT scoring systems.
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There was no advantage of performing a CT on admission
as an independent predictor over the more easily
obtainable clinical scoring systems in terms of accuracy in
predicting clinically severe AP and mortality

There are several potential explanations for the observed
mode rate accuracy for clinical severity and mortality
using CT scoring systems.

First, the anatomic extent of pancreatic inflammation and
the size and volume of peripancreatic fluid collections are
not included in any of the studied scoring systems; both
peripancreatic fat stranding and fluid collections can range
from discrete to extensive in magnitude, but are accorded
equal points in the studied scoring systems.

Second, some patients initially predicted to have mild AP
may, nonetheless, progress to clinically severe AP over the
initial 48 h of hospitalization along with worsening
morphologic changes on imaging.

A substantial number of patients with pancreatic necrosis
established on admission CT (25 % in the present study
and 38 % in a study by Casas et al.) did not develop
clinically severe disease. It remains poorly understood
why differentclinical courses are observed in patients
with significant pancreatic parenchymal necrosis.

Scoring systems work best at the extremes of the
spectrum (i.e., high negative or positive predictive value
in patients with very low or high scores), whereas the
performance of these scoring systems is only moderate in
intermediate scores.

In five previous studies, all showed a moderate positive correlation
between CT score and mortality and morbidity.

A comparison of our results with those of previously published
studies is difficult for several more reasons. First, no clear definition
of clinical severity of disease has been consistently applied. Second,
different threshold values, as opposed to ROC curve analysis, were
used to predict clinical severity. It is generally acknowledged that
the overall performance of a test and comparison of prognostic
scoring systems is best performed using ROC curve analysis, which
was only one study. Third, only one of these studies performed
comparative analysis between the CT scoring systems

and no studies compared the radiologic systems with clinical scoring
systems.

Although this study highlights the prognostic accuracy of
CT, we feel that a more judicious use of CT in AP is
warranted .

This study showed that early CT did not reveal any other
diagnosis, did not reveal any local pancreatic complication,
and underestimated the presence of parenchymal necrosis
in a substantial number of patients.

Hence, we recommend that CT studies should be reserved
only for those patients with predicted severe AP by clinical
assessment, for those who fail to improve clinically with
conservative management or those in whom the diagnosis
is unclear or a severe complication is suspected (such as
bleeding, bowel ischemia, or perforation).
LIMITATIONS

First, not all patients admitted or transferred to our
hospital underwent a CT on the day of admission. Instead,
CT was performed based on the discretion of treating
physician (primarily for severity assessment) and,
therefore, our methodology reflects, in some respects,
current clinical practice.

Second, there were a relatively small number of severe
cases. However, this study was the largest so far to
compare the use of different CT and clinical prognostic
scoring systems on the day of admission. In addition, the
prevalence of mild and severe cases in our study (82 % and
18 % , respectively) is similar to the literature ( 1 ).
CONCLUSION

Our study did not detect significant differences between
any of the seven studied CT scoring systems in predicting
mortality and clinical severity of AP.

Moreover, CT scoring systems were not superior to the
studied clinical scoring systems.

There appears to be no advantage of performing a CT on
admission for prognostic purposes compared with the
simpler and more easily obtained clinical scoring systems
and, therefore, obtaining a CT for assessment of severity on
the day of admission is not recommended.
Thank you for
your attention