ARTICLE IN PRESS

Surgery ■■ (2017) ■■–■■

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Surgery
j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / y m s y

Validation of the AAST EGS acute cholecystitis grade and comparison

with the Tokyo guidelines
Matthew Hernandez a,*, Brittany Murphy a, Johnathan M. Aho a, Nadeem N. Haddad b,
Humza Saleem a, Muhammad Zeb a, David S. Morris c, Donald H. Jenkins b, and
Martin Zielinski a
a Division of Trauma, Critical Care and General Surgery, Mayo Clinic, Rochester, MN, USA
b
Division Trauma and Emergency Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
c
Division of General Surgery, Trauma, and Critical Care, Intermountain Medical Center, Murray, UT, USA

A R T I C L E I N F O A B S T R A C T

Article history: Background. Acute cholecystitis presents with heterogeneous severity. The Tokyo Guidelines 2013 is a
Accepted 25 October 2017 validated method to assess cholecystitis severity, but the variables are multifactorial. The American As-
sociation for the Surgery of Trauma (AAST) developed an anatomically based severity grading system
for surgical diseases, including cholecystitis. Because the Tokyo Guidelines represent the gold standard
to estimate acute cholecystitis severity, we wished to validate the AAST emergency general surgery scoring
system and compare the performance of both systems for several patient outcomes.
Methods. Adults (≥18 years) with acute cholecystitis during 2013–2016 were identified. Baseline de-
mographic characteristics, comorbidity severity as defined by Charlson Comorbidity Index score, procedure
types, and AAST and Tokyo Guidelines 2013 grades were abstracted. Outcomes included duration of stay,
30-day mortality, and complications. Comparison of the Tokyo Guidelines and AAST grading system was
performed using receiver operating characteristic (AUROC) curve C statistics.
Results. There were 443 patients, with a mean (±standard deviation) age of 64.8 (±18) years, 59% male.
The median (interquartile ratio) Charlson Comorbidity score was 3 (0–6). Management included lapa-
roscopic (n = 307, 69.3%), open (n = 26, 6%), laparoscopy converted to laparotomy (n = 53, 12%), and
cholecystostomy (n = 57, 12.7%). Comparison of AAST with Tokyo Guidelines AUROC C statistics indi-
cated (P < .05) mortality (0.86 vs 0.73), complication (0.76 vs 0.63), and cholecystostomy tube utilization
(0.80 vs 0.68).
Conclusion. Emergency general surgery grading systems improve disease severity assessment, may improve
documentation, and guide management. Discrimination of disease severity using the AAST grading system
outperforms the Tokyo Guidelines for key clinical outcomes. The AAST grading system requires prospec-
tive validation and further comparison.
© 2017 Elsevier Inc. All rights reserved.

Accurate measurement of disease severity may provide impor-
tant prognostic information to clinicians to optimize care and
accurately counsel their patients.1 Acute cholecystitis typically pres-
ents with significant variability and can be treated relatively simply
through surgical resection with low morbidity and mortality if di-
agnosed early.2-4 Conversely, it can be associated with significant
No conflicts of interest in the design and reporting of the manuscript.
This publication was made possible by CTSA grant KL2 TR000136 (Zielinski) from
the National Center for Advancing Translational Sciences (NCATS), a component of
the National Institutes of Health.
Presented at the 47th World Congress of Surgery, IAT/SIC Prize Competition,
August 13–17, 2017, Basel, Switzerland.
* Corresponding author. Division of Trauma Critical Care and General Surgery,
Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
E-mail address: hernandez.matthew@mayo.edu (M. Hernandez).
morbidity and mortality if disease progression occurs.5 Defining
disease severity therefore is important to accurately understand and
improve outcomes related to individual disease severity states.6 This
need for a standardized methodology to enhance diagnosis accu-
racy was the impetus for the development of the Tokyo Guidelines
(TG) (Table 1).7,8 Extensive previous work has elucidated and peri-
odically redefined criteria for the accurate diagnosis of acute
cholecystitis and cholangitis.9-13 Furthermore, the standardized TG
nomenclature permitted optimization of operative and nonoperative
management for various grades of acute calculous cholecystitis.7,12-14
The Tokyo Guidelines are a proven methodology to assign severity
in acute cholecystitis, the stepwise approach to securing a defini-
tive diagnosis using patient physiologic parameters and symptoms.
A more universal anatomic severity grading system focusing on dis-
tinct anatomic changes may be more accurate and take into account
objective findings for different levels of care—imaging, physiologic,

https://doi.org/10.1016/j.surg.2017.10.041
0039-6060/© 2017 Elsevier Inc. All rights reserved.

Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
 ARTICLE IN PRESS
2 M. Hernandez et al. / Surgery ■■ (2017) ■■–■■

Table 1 anatomically based framework to uniformly risk adjust and compare

The Tokyo guidelines grade descriptions of acute cholecystitis severity.
Grade Description
Grade I (mild) Acute cholecystitis without organ dysfunction
Grade II Associated with any single following conditions
(moderate) WBC > 180,000/mm3
Palpable tender mass in right upper quadrant
Symptoms longer than 72 hours
Marked local inflammation (gangrenous cholecystitis,
pericholecystic abscess, hepatic abscess, biliary peritonitis,
emphysematous cholecystitis)
Grade III Associated with any organ dysfunction of the following:
(severe) Cardiovascular: Hypotension requiring vasopressors
Neurologic: Decreased level of consciousness
Respiratory: PaO2/FiO2 < 300
Renal: Oliguria, creatinine > 2.0 mg/dL
Hepatic: PT-INR > 1.5
Hematologic: Platelets < 100,000/mm3
PT-INR, prothrombin time–international normalized ratio; WBC, white blood cell.
operative, and pathologic.15 Although these American Association
for the Surgery of Trauma (AAST) emergency general surgery (EGS)
grades may not be intended to initially serve alone as predictors
of outcome, their use, coupled with patient comorbidity and acute
physiology measures, may provide enhanced discernment of disease
severity.
The AAST developed a clinical, radiologic, operative, and patho-
logic grading system for EGS diseases, including acute cholecystitis
(Table 2, Fig 1).1,16-19 Previous work incorporating this methodolo-
gy identified the validity and applicability in management and
related clinical outcomes for similar EGS diseases.18-21 The goal of
the AAST EGS grading system is to provide a consistent and
outcomes among different centers. Standard categorization of acute
cholecystitis, as provided by the AAST EGS grading system, is similar
to the TG in that it is used to assess disease severity at presenta-
tion and can be modified based on intraoperative findings. Although
the TG requires a stepwise method to assign disease severity, the
AAST grading system uses individualized anatomically driven injury
patterns to correspond with disease severity.16 Universal adoption
of any grading system, such as the AAST EGS or TG grade, may lead
to improved prognostication of outcomes, risk stratification, im-
proved management, cost containment, and reimbursement analysis
across the health care spectrum.22
Comparison and critical evaluation of these scoring systems is
needed to standardize disease severity and management. The present
study aims to validate the AAST EGS grading system for acute cho-
lecystitis and perform a quantitative comparison of the AAST EGS
grading system with the current international standard TG. We hy-
pothesize that both the AAST EGS and TG grading systems will be
valid in our population. Moreover, the AAST EGS grading system will
comparable to the TG in predicting disease severity, defined as mor-
tality, development of a complication, and need for cholecystostomy.
Methods
Patient inclusion and data collection
This is a retrospective single-institution study of patients 18 years
or older that were diagnosed with acute calculous cholecystitis who
were admitted to our EGS service during 2013–2016. Institutional
Review Board approval was obtained before data collection and

Table 2
AAST EGS grade descriptions of acute cholecystitis severity.

Grade Description Imaging Operative

Grade I Localized gallbladder inflammation Wall thickening, pericholecystic fluid, Localized inflammatory changes
nonvisualization of the gallbladder
Grade II Distended gallbladder with purulence or hydrops, Above plus air in the gallbladder lumen, wall Distended gallbladder with pus/hydrops,
necrosis/gangrene of wall noted without iatrogenic or biliary tree nonperforated wall necrosis/gangrene
perforation
Grade III Noniatrogenic perforation with bile located to RUQ Extraluminal fluid collection limited to RUQ Noniatrogenic gallbladder wall perforation
with bile limited to RUQ
Grade IV Pericholecystic abscess, bilioenteric fistula, gallstone RUQ abscess, bilioenteric fistula, gallstone ileus Pericholecystic abscess, bilioenteric fistula,
ileus gallstone ileus
Grade V Grade IV disease but with generalized peritonitis Free intraperitoneal fluid Above with generalized peritonitis

RUQ, right upper quadrant.

Fig. 1. AAST EGS acute cholecystitis grade.

Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
 ARTICLE IN PRESS
M. Hernandez et al. / Surgery ■■ (2017) ■■–■■
analysis. Retrospective identification of patients with acute chole-
cystitis at admission was included. Exclusion criteria included active
pregnancy, biliary obstruction secondary to malignancy, age younger
than 18 years, and patients receiving interval cholecystectomy at
a later hospital stay. After patients had a diagnosis secured, the acute
care surgeon on call made the decision for operative or nonoperative
management.
Baseline demographic information was abstracted including
age, sex, body mass index, race/ethnicity, concurrent comorbidity
status as assigned by the Charlson Comorbidity Index, complica-
tion type as defined by National Surgical Quality Improvement
Program variables,23 complication severity as defined by the Clavien-
Dindo classification system, 24 operative and nonoperative
management types, postprocedure endoscopic retrograde
cholangiopancreatography, and 30-day mortality (from the time
of dismissal).
TG 2013 grade assignment and validation in our cohort
The TG are a clinical stratification tool used for the accurate as-
signment of disease severity in patients with acute cholecystitis and
cholangitis.15 The disease severity criteria are referenced in Table 1.
Two reviewers (N.N.H., H.S.) assigned TG severity grades to each par-
ticipant. A third reviewer (M.C.H.) resolved any discrepancies. The
grading system is as follows: I (mild acute cholecystitis), II (mod-
erate acute cholecystitis), and III (severe acute cholecystitis).
Information regarding patient medical history, physical examina-
tion, ultrasound findings, and laboratory values (white blood cell
count, international normalized ratio, complete blood cell count)
as well as vasopressor use or mechanical ventilator status were ab-
stracted. These data were used to assess the disease severity.
AAST grade assignment and validation in our cohort
The disease severity of acute cholecystitis was assigned an AAST
grade as outlined in Table 2.15 Disease severity ranges from grade I
(mild, localized inflammation) to grade V (severe, generalized in-
flammation). Fig 1 represents a cartoon depiction of the AAST EGS
grades for acute cholecystitis. Here we can see incremental stages
of inflammation with AAST EGS grades III, IV, and V correspond-
ing to increasingly severe stages of perforation. Grades were assigned
by 2 independent reviewers (N.N.H., H.S.). A third reviewer (M.C.H.)
resolved any discrepancies. Grades were generated from opera-
tive, pathologic, and ultrasonography findings. The operative criteria
were determined from both the surgical operative note and the res-
ident postoperative note. Findings that correlated with specific AAST
EGS grades were determined and an AAST EGS operative grade was
assigned. The preoperative ultrasonography grade was used for all
statistical purposes. The imaging AAST EGS grade was assigned by
reviewing the ultrasonography reports and images using the cri-
teria for imaging. The presence of a fistula, pericholecystic abscess,
or gallstone ileus differentiated AAST EGS grade IV from grade III.
The operative and pathologic grades were used to confirm preop-
erative ultrasonography findings. Ultrasonography was interpreted
by an attending radiologist. The level of agreement between the
imaging and operative AAST EGS grades was calculated using the
κ coefficient with 95% confidence intervals (CI).
Statistical analysis
Descriptive statistics were used for baseline demographic char-
acteristics, clinical outcomes, and AAST/TG grading systems. The
diagnostic accuracy of each scoring system for mortality, compli-
cation development and complication severity, and procedural
Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
3
outcomes was assessed using area under the receiver operating char-
acteristic curves (AUROC) with 95% CIs. Pairwise comparisons of
AUROCs were assessed using the difference between the areas, 95%
CI and P values. The comparisons were performed using an ap-
proach described by Hanley and McNeil.25 This method provides the
ability to describe and compare the performance of diagnostic al-
gorithms by accounting for the correlation between the paired nature
of the AAST and TG with the selected outcomes. After applying the
TG and AAST EGS grades, the AUROC analysis was performed to de-
termine which score more accurately predicted outcomes.
Univariate and multivariable analyses with odds ratios and 95%
CIs to determine significant predictors for clinical outcomes were
completed for both TG and AAST using the following variables: mor-
tality, morbidity, complication severity (Clavien-Dindo), duration of
stay, increasing patient age, increasing Charlson Comorbidity score,
male sex, need for cholecystectomy, need for cholecystostomy, open
procedures, and conversion from laparoscopic to open procedures.
All continuous variables were described using means with stan-
dard deviations if normally distributed and medians with
interquartile ranges (IQRs) if gross skewness was present. Categor-
ical variables were summarized as proportions. To associate the AAST
EGS grade, Cochran Armitage test for trend was used for categor-
ical variables and Spearman correlation for continuous variables was
used. All data analyses were performed using JMP (SAS Institute,
Inc. Cary NC). We used GraphPad Prism 7 (GraphPad Software, Inc.
La Jolla CA) for all visual graphics.
Results
Overall demographics
A total of 443 patients were identified. The cohort had a mean
age of 64.8 (±18) years and 59% were male. Median (IQR) patient
comorbidities using the Charlson Comorbidity score was 3 (0–6).
Operative types and rates included open (n = 26, 6%), laparoscopic
(n = 307, 69%), and laparoscopic converted to open (n = 53, 12%), with
57 patients (13%) undergoing nonoperative management with cho-
lecystostomy tube placement. Thirty-day mortality rate was 5.8%.
Overall complication rate reported using National Surgical Quality
Improvement Program (NSQIP) styled complication types was 30.9%.
The overall patient race/ethnicity within this cohort was white (83%),
Asian (8%), black (4%), Hispanic (3%), and Native American (2%). The
imaging and operative AAST EGS grades indicated strong agree-
ment with a κ coefficient of 0.83 and 95% CI (0.79–0.88).
Validation of the AAST grading system
On univariate analysis, increasing anatomic severity according
to the AAST grading system was significant with the following vari-
ables (P < .05): mortality, morbidity, complication severity (Clavien-
Dindo), duration of stay, increasing patient age, increasing Charlson
Comorbidity score, male sex, need for cholecystectomy, need for cho-
lecystostomy, open procedures, and conversion from laparoscopic
to open procedures (Table 2). On multivariable analysis, patients with
increasing disease severity relative to grade I were more likely to
develop a postoperative complication; grade III disease had an odds
ratio (OR) of 3.2 (1.4–5.2) and further for grade IV disease 4.5 (3.3–
7.7) and grade V disease 8.6 (6.1–10.4). Additional independent
factors associated with postoperative complication included age older
than 65 years (OR 1.3; 95% CI 1.1–2.2) and laparoscopic converted
to laparotomy procedures (OR 4.9; 95% CI 2.3–7.1). With regard to
inter-rater reliability, the κ coefficient between reviewers was 0.82
(95% CI, 0.74–0.85). There was no systematic difference in the as-
signment of AAST grades because the P value for test of symmetry
was 0.98. Further, of the patients undergoing operative manage-
ment, confirmation of histologic evidence for acute cholecystitis was
 ARTICLE IN PRESS
4 M. Hernandez et al. / Surgery ■■ (2017) ■■–■■

Table 3
Patient characteristics, procedure types, and outcomes by disease severity using the AAST grade.

Variable Grade I Grade II Grade III Grade IV Grade V P value

n = 154 n = 148 n = 81 n = 46 n = 14

Patient characteristics
Age 66 (53–79) 61 (50–75) 71 (61–81) 70 (56–78) 75 (64–81) .02
% Male 48.7 60 70 71 64 .01
Charlson Comorbidity Index 2 (0–5) 2 (0–5) 4 (2–7) 4 (2–6) 6 (3–7) .001
Systolic blood pressure 136 (122–151) 117 (10–131) 120 (107–135) 121 (106–142) 121 (89–144) .001
Heart rate 88 (85–95) 89 (80–97) 96 (80–111) 102 (85–120) 104 (88–123) .1
Temperature 36.7 (36–37) 36.7 (36.4–37) 37.3 (36.7–38) 37.1 (36.3–38) 38 (37–38.9) .001
White blood cell count 12.4 (9.6–14.8) 13.4 (10–16) 16 (13–19) 15.2 (12–19) 20.3 (13.8–24.8) .001
Initial procedural data
Laparoscopic cholecystectomy 91 76 52 24 7 .001
Open cholecystectomy 2.6 2.7 7.4 21.7 15 .001
Laparoscopic converted to open procedure 3.9 12.8 16 26.1 21.4 .001
Cholecystostomy tube placement 3.2 8.1 34.5 39.1 71.4 .001
Outcomes
Duration of stay 3 (2–4) 3 (2–5) 5 (3–7) 5 (3–7) 12 (4–12) .001
Clavien-Dindo grade
I 33.3 23.8 33.3 4.8 4.7 .001
II 7.4 14.8 44.4 18.5 14.8 .001
III 21.4 28.5 28.5 21.4 0 .001
IV 7.5 32 30.1 22.6 7.5 .001
V 1.9 1.3 9.8 17.4 35.7 .001

P value refers to Cochran Armitage test for trend for categorical variables and Spearman correlation for continuous variables.

found in 357 (92%) of patients. The remaining patients (n = 29) had
chronic cholecystitis and were found to all have a preoperative AAST
grade of I (Table 3).
Validation of the TG grading system
On univariate analysis, the following variables were associated
with increasing acute cholecystitis severity based on the TG (P < .05):
mortality, morbidity, complication severity (Clavien-Dindo), dura-
tion of stay, increasing patient age, increasing Charlson Comorbidity
score, male sex, need for cholecystectomy, need for cholecystos-
tomy, open procedures, and conversion from laparoscopic to open
procedures (Table 4). Multivariable analysis indicated that inde-
pendent features associated with postoperative complications
included TG grade II (OR 1.8; 95% 1.2–3.4) and TG grade III (OR 4.9;
95% CI 2.7–9.1) and laparoscopic converted to laparotomy proce-
dures (OR 2.9; 95% 1.2–8.2; Table 4). In addition, the ability to reliably
assign disease severity by the reviewers had a κ coefficient of 0.77
(95% CI, 0.71–0.81), and the P value for test of symmetry was .99.
Complications and grades
Table 5 highlights complication data for increasing disease se-
verity. Increasing disease severity was associated with increasing
complication severity. There were fewer cystic duct stump leaks and
postoperative choledocholithiasis in lower AAST grade disease cat-
egories. For increasingly severe acute cholecystitis, there were more
postoperative mortalities, surgical site infections, development of
acute kidney injury, and rate of developing sepsis.
AUROC analyses comparing AAST with TG grades
Fig 2 outlines the comparisons of AUROCs for AAST and TG grades
and their associations in describing mortality, morbidity, and need

Table 4
Patient characteristics, procedure types, and outcomes by disease severity using the Tokyo Guidelines.

Variable Grade I Grade II Grade III P value

n = 347 n = 72 n = 24

Patient characteristics
Age 65 (45–78) 70 (54–81) 75 (63–80) .1
% Male 57.6 62.5 71 .3
Charlson Comorbidity Index 3 (0–5) 4 (2–6) 6 (3–7) .001
Systolic blood pressure 127 (113–142) 120 (105–135) 117 (99–138) .01
Heart rate 98 (82–111) 100 (82–112) 103 (79–109) .9
Temperature 36.8 (36.4–37.2) 37.3 (36.7–38) 37.2 (36.5–38.1) .01
White blood cell count 13.6 (10.1–16.6) 15.2 (12.2–18.9) 15.1 (9.8–20.7) .02
Initial procedural data
Laparoscopic cholecystectomy 78.4 40.3 25 .001
Open cholecystectomy 3.7 14 12.5 .001
Laparoscopic converted to open procedure 10 19.4 16.6 .06
Cholecystostomy tube placement 10.1 36.11 50 .001
Outcomes
Duration of stay 3 (2–5) 5 (3–7) 11 (5–14) .0001
Clavien-Dindo grade
I 5.2 2.7 4.1 .01
II 3.5 17 12.5 .01
III 3.1 1.4 8.3 .01
IV 9.5 15.2 37.5 .01
V 3.1 12.5 25 .01

P value refers to Cochran Armitage test for trend for categorical variables and Spearman correlation for continuous variables.

Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
 ARTICLE IN PRESS
M. Hernandez et al. / Surgery ■■ (2017) ■■–■■ 5

Table 5
Complication types n, (%) and association with AAST grade.

Complication type Grade I Grade II Grade III Grade IV Grade V

n = 20 n = 26 n = 50 n = 28 n = 13

Hematoma 1 (5) 1 (3) 1 (2) 1 (4) 0

Atrial fibrillation 4 (20) 3 (13) 2 (4) 1 (4) 1 (8)
Iatrogenic bowel injury 1 (5) 0 0 0 0
Sepsis 1 (5) 3 (13) 7 (14) 3 (10) 2 (15)
Superficial SSI 3 (15) 3 (13) 6 (12) 1 (4) 1 (8)
Deep SSI 0 1 (3) 4 (8) 0 0
Organ space SSI 0 0 2 (4) 2 (7) 0
Small bowel obstruction 1 (5) 0 0 0 0
Biloma 1 (5) 0 2 (4) 0 0
Urinary retention 1 (5) 1 (3) 2 (4) 0 0
Respiratory failure 2 (10) 1 (3) 5 (10) 1 (4) 1 (8)
Death 3 (15) 1 (3) 8 (16) 8 (28) 5 (38)
Postoperative hemorrhage 0 0 2 (4) 1 (4) 0
Cystic stump leak 0 3 (13) 2 (4) 1 (4) 0
Retained choledocholithiasis 0 3 (13) 0 2 (7) 0
Cholangitis 0 1 (3) 0 1 (4) 0
Acute kidney injury 0 1 (3) 4 (8) 6 (20) 2 (15)
Pneumonia 1 (5) 2 (8) 0 0 0
Ileus 0 0 2 (4) 0 0
Urinary tract infection 1 (5) 1 (3) 0 0 1 (8)
Upper gastrointestinal bleed 0 1 (3) 1 (2) 0 0

SSI, surgical site infection.

Fig. 2. Area under the receiver operating curves comparing AAST and TG disease severity scores with key clinical outcomes.

for cholecystostomy. The AAST grade indicated enhanced ability, Discussion

compared with TG, for the associations with the following clinical
outcomes: mortality (0.80; 95% CI: 0.75–0.83 vs 0.71; 95% CI: 0.67–
0.73, P = .003), overall complications (0.74; 95% CI: 0.70–0.78 vs 0.64;
95% CI: 0.58–0.68, P = .001), and cholecystostomy use (0.73; 95% CI:
0.71–0.79 vs 0.67; 95% CI: 0.62–0.70, P = .02).
Acute care surgeons are responsible for a wide spectrum of sur-
gical patients with outcomes often dependent on disease severity,
comorbidity status, and acute physiologic changes.26 In the present
study, we found that both the Tokyo Guidelines and AAST grades

Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
 ARTICLE IN PRESS
6 M. Hernandez et al. / Surgery ■■ (2017) ■■–■■
were able to describe disease severity; however, when comparing
both systems with key clinical outcomes, the AAST grade appears
to be more highly correlated. Our results confirm our hypotheses
that both the AAST and TG grades would be valid in our popula-
tion but that the AAST grade outperforms the TG for postoperative
mortality, complication development, and the need for preopera-
tive cholecystostomy. Patients with acute cholecystitis remain a daily
challenge due to heterogeneous presentation and this has made stan-
dardization of therapeutic algorithms difficult.1,27 Because the current
era of surgery increasingly used clinical decision pathways, appli-
cation of universal imaging, clinical, operative, and pathologic
definitions are necessary to guide evidence-based treatment.11 The
diverse presentation of acute cholecystitis emphasizes the need to
standardize documentation of disease severity in a simple and re-
producible manner.7
Development of grading systems for the routine documenta-
tion of disease severity in a given patient will be increasingly
important. Previously, the TG were developed, implemented, and
refined to improve prognostic accuracy related to complications as-
sociated with acute cholecystitis and its treatment.9 This method
uses several clinical, physiologic, laboratory, and imaging-based mo-
dalities to incrementally describe disease severity in a patient. All
of the facets of disease severity as described by the TG may be stated
in a clinically translatable way through uniform anatomic injury clas-
sifications using the AAST grade.
The ability to make an efficient and accurate diagnosis as well
as assign a severity grade at the bedside in a disease-specific manner
is crucial. With a secure diagnosis for any EGS disease, the AAST
created an accurate disease severity grading system that can be
calculated from a patient’s anatomic injury, in this case from ul-
trasonography for acute cholecystitis.15 Whereas the TG provides
diagnostic criteria to aid in clinical decision making, the AAST grade
solely assigns disease severity. These tools were developed for dif-
ferent goals; however, they are complementary. The TG provides a
diagnostic method, whereas the AAST grade assigns disease sever-
ity after the diagnosis has been made. Both systems aim to provide
a severity measurement; however, the AAST grading system does
not stipulate the means with which a diagnosis of acute cholecys-
titis is made. The TG focus on a stepwise laboratory, clinical, and
imaging-based pathway, unlike the AAST grade, which is based on
preoperative imaging findings alone. A potential explanation for the
increased discrimination of the AAST system compared with the TG
is the 5 levels rather than 3 to describe disease severity. The gran-
ular description of increasing anatomic findings by the AAST grade
provides improved classification of severity as opposed to a mild,
moderate, or severe disease state.
Before the development of the TG, there was no reliable method
to assign diagnostic criteria and subsequent disease severity for acute
cholecystitis. Surgical decision making was based on individual
surgeon assessments. The TG provides a classification method that
evaluates treatment approaches while controlling for disease se-
verity. TG revisions incorporating physiology and clinical status of
the patient have aimed to improve TG disease severity assess-
ment with preoperative status, management approach, and
postoperative events.12,13,28 Although these efforts to refine the TG
continue to evolve, Ambe et al29 found that TG preoperative sever-
ity did not necessarily correlate with histopathologic severity,
suggesting that a more anatomically based description of disease
severity may better correlate with outcomes. A major limitation of
TG clinical application is the need for these multifactorial data.30
In our cohort, for the patients who underwent cholecystectomy, the
majority of the patients displayed acute cholecystitis. This histo-
pathologic analysis strengthens the internal validity of the
preoperative ultrasonography-generated AAST grade.
Surgical disease risk assessment is ideally designed to aid the
clinician in the preoperative setting. The TG suggest various
Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
management approaches for increasing disease severity: mild (grade
I) receive early laparoscopic cholecystectomy, moderate (grade II)
receive fluid and antimicrobial resuscitation with early or delayed
cholecystectomy, and severe (grade III) disease is often associated
with organ failure, which necessitates percutaneous drainage. Loozen
et al31 reported no difference in perioperative outcomes for grade
I and grade II disease as assigned by the 2013 TG, suggesting no need
for delayed laparoscopic cholecystectomy and that early cholecys-
tectomy could be performed. In our analysis, most patients
underwent cholecystectomy. The inclusion of increasingly severe
disease states, AAST grade IV and V, permits a more inclusive anal-
ysis than the TG, which assign greater disease severity through
physiologic insult. Applying the AAST grade appears to more ro-
bustly correspond with outcomes compared with the TG and appears
to apply in concept to all EGS diseases, therefore making it a unified
system.
Our analysis provides insight into the complications encoun-
tered with increasing disease severity in granular detail. The finding
that increased disease severity is associated with increased mor-
bidity is not novel. Emergent and urgent surgery is associated with
an increased burden of complications and requires increasing sur-
gical support.32 In this cohort, we found a 5.8% 30-day mortality rate.
In comparison, Yokoe et al,10 using multinational data, reported sub-
stantially lesser mortality rates of 1.1% and 1.3% at 90 days.10 This
difference is a significantly increased rate of mortality but high-
lights the severity within our referred study population. Patients
present with worse severity, comorbidity status, and physiology, all
of which may contribute to postoperative outcome. Moreover, the
patients who died typically underwent cholecystostomy before cho-
lecystectomy, suggesting that other comorbid and physiology features
prevented early cholecystectomy. Provision of adequate surgical care
for acute cholecystitis and its attendant morbidity is necessary and
requisite of acute care surgeons. Application and documentation of
disease severity is going to be important for clinicians in the future.
Because payment models are in a state of transition and the reim-
bursements are increasingly less fee for service, documenting the
disease severity early will help clinicians in the management of pa-
tients and potential complications, as well as be reimbursed for
potentially more severe disease.33,34
Recent work examines the comparability of the TG to the Amer-
ican College of Surgeons surgical risk calculator (ACS-NSQIP).35 In
this work, the authors used aggregate data to indicate that the ACS-
NSQIP risk calculator did not correlate with postoperative outcomes
and the TG were only able to describe duration of stay. In our cohort,
however, the AAST grade correlated with several physiologic, man-
agement, and postoperative outcomes. This work underscores efforts
to validate the AAST grading system for acute cholecystitis while
comparing with current disease severity classification (TG). Grade
for grade, increasing anatomic injury in acute cholecystitis is as-
sociated with worse clinical and postoperative outcomes. Although
the aggregate data analysis comparing the TG and the ACS-NSQIP
did not indicate significant correlation of the disease severity and
outcomes, our analysis of disease severity and outcomes corre-
lated with the AAST grade and the TG.35 Although our present study
highlights the potential power of both the AAST and TG grading
systems, the AAST grading system is superior with greater asso-
ciations for key clinical outcomes. The ability to rapidly assign disease
severity from degree of anatomic injury is (1) simple to calculate,
(2) does not require multiple laboratory values, and (3) does not
require development of organ failure to associate with outcome.
Dimou et al36 performed a propensity score–matched evalua-
tion of patients receiving cholecystostomy and determined that the
majority of patients did not get definitive cholecystectomy but had
concomitant increased readmission and mortality rates. At our in-
stitution, we use percutaneous cholecystectomy for patients with
severe comorbidities preventing operative management or in those
 ARTICLE IN PRESS
M. Hernandez et al. / Surgery ■■ (2017) ■■–■■
for whom operative management may be temporarily precluded
because of acute cholecystitis severity. For the patients managed
with percutaneous cholecystostomy, the majority displayed in-
creased disease severity (AAST grades IV and V) with an increased
comorbid state. Use of this less invasive technique provides an ac-
ceptable alternative for the appropriate patient population. Previous
reports describe gangrenous or perforated acute cholecystitis and
compare them with patients with less severe disease. Yeh et al5 found
that, for patients with gangrenous cholecystitis, assessing disease
severity with ultrasound is difficult. The authors reported that for
gangrenous cholecystitis there were increased rates of laparos-
copy converted to open procedures and duration of stay of 4 days.
Although we describe the ability to categorize disease severity using
preoperative ultrasonography, our data also reflect increased rates
of conversion to open procedures and similar duration of stay for
comparable disease states (AAST grade II).
There are several future directions. First, we are implementing
routine clinical, imaging, operative, and pathologic AAST EGS grading
for several conditions to perform a prospective validation study.
Further, we plan on comparing patients in different clinical envi-
ronments such as rural versus urban as well as different
socioeconomic settings. It is likely that the AAST EGS grade may be
more aptly assigned in this setting or potentially serve as a tool to
improve triage for EGS patients (transfer to higher levels of care or
receive immediate operative intervention). We also plan to perform
a prospective study wherein management (cholecystostomy, oper-
ation, or antibiosis alone) is stratified by AAST EGS grade. Finally,
we aim to perform a prospective observational trial validating ul-
trasonography compared with other cross-sectional imaging methods
to diagnose acute cholecystitis using the AAST EGS definitions. All
of these hypotheses are important and testable; however, depend
on initial validity of the AAST EGS grade and widespread adoption.
Our study has several limitations. This study is a retrospective
review of patients with the diagnosis of acute cholecystitis, which
induces selection bias. We attempted to address this by including
patients undergoing both operative and nonoperative approaches;
yet our cohort may not be representative of the general popula-
tion, with the potential for institutional referral bias. As a quaternary
referral center, patients typically are referred for greater per-
ceived disease severity and advanced comorbidities. There is also
operator dependency for abdominal ultrasonography. Despite this,
there was an 88% concordance of acute cholecystitis diagnosed on
pathologic examination to the preoperative AAST grade. Differen-
tiating AAST EGS grades I and II with ultrasonography may be
confounded by presence of air or nearby luminal structures. Our
finding that there was a strong agreement between imaging and
operative grades, however, suggests that the ultrasonography may,
with some accuracy, describe operative findings. Furthermore, al-
though there is no prospective study to provide external and
construct validity of the AAST grade, our retrospective analysis con-
firms the validity of the TG and the authors submit that this serves
as a check confirming that incremental disease severity is well de-
scribed by the AAST grade. Finally, there is likely a degree of
demographic bias; our population is overwhelmingly Caucasian, and
these results may not be generalizable to regions with more varied
ethnicity where incidence of gallbladder disease may be different.
Conclusion
Our study detected significant improvement of the AAST system
compared with the TG system for associations with mortality, mor-
bidity, and need for cholecystostomy in acute cholecystitis favoring
the AAST grading system. Preoperative assignment of disease se-
verity is possible using ultrasonography alone and is associated with
several outcomes analyzed in this study. Further study of the AAST
Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041
7
grading system evaluating different aspects of acute cholecystitis
and cholangitis prospectively are required.
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Please cite this article in press as: Matthew Hernandez, Brittany Murphy, Johnathan M. Aho, Nadeem N. Haddad, Humza Saleem Muhammad Zeb, David S. Morris, Donald H. Jenkins,
and Martin Zielinski, Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines, Surgery (2017), doi: 10.1016/j.surg.2017.10.041