http://dx.doi.org/10.1016/j.hpb.2016.10.

006 HPB

ORIGINAL ARTICLE

Same admission laparoscopic cholecystectomy for acute

cholecystitis: is the “golden 72 hours” rule still relevant?
Jarrod K.H. Tan1, Joel C.I. Goh2, Janice W.L. Lim2, Iyer G. Shridhar1, Krishnakumar Madhavan1
& Alfred W.C. Kow1
1
Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System,
and 2Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Abstract
Background: Studies have shown that same admission laparoscopic cholecystectomy (SALC) is su-
perior to delayed laparoscopic cholecystectomy for acute cholecystitis (AC). While some proposed
a“golden 72-hour” for SALC, the optimal timing remains controversial. The aim of the study was to
compare the outcomes of SALC in AC patients with different time intervals from symptom onset.
Methods: A retrospective analysis of 311 patients who underwent SALC for AC from June 2010–June
2015 was performed. Patients were divided into three groups based on the time interval between
symptom onset and surgery: <4 days (E-SALC), 4–7 days (M-SALC), >7 (L-SALC).
Results: The mean duration of symptoms was 2(1–3), 5(4–7) and 9 (8–13) days for E-SALC, M-SALC
and L-SALC, respectively (p < 0.001). Conversion rates were higher in the L-SALC group [E-SALC, 8.2%
vs M-SALC, 9.6% vs L-SALC, 21.4%] (p = 0.048). The total length of stay was longer in patients with
longer symptom duration [E-SALC, 4 (2–33) vs M-SALC, 2 (2–23) vs L-SALC, 7 (2–49)] (p < 0.001).
Conclusion: Patients with AC presenting beyond 7 days of symptoms have higher conversion rates and
longer length of stay associated with SALC. However, patients with less than a week of symptoms
should be offered SALC.

Received 4 September 2016; accepted 12 October 2016

Correspondence
Alfred W.C. Kow, Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, University
Surgical Cluster, National University Hospital, 1E, Kent Ridge Road, NUHS Tower Block, Level 8, 119228,
Singapore. E-mail: alfred_kow@nuhs.edu.sg

Introduction nature, early SALC from within 24–72 h of symptom onset has
been associated with decreased intra-operative morbidity, with a
The management of acute cholecystitis (AC) has undergone a
resultant shorter hospital length of stay.8–11
paradigm shift in recent years, with an increasing preference for
With increasing proficiency in minimally invasive surgery
same admission (SALC) over delayed (DLC) laparoscopic cho-
(MIS) in recent years, SALC becomes an attractive option for
lecystectomy.1 Existing literature has convincingly shown that
patients with acute cholecystitis. Existing studies that analyze the
compared to DLC, SALC decreases overall hospital length of stay
learning curve of LC have established a significant decrease in
and eliminates the risks of gallstone-related morbidity while
duration of operation and post-operative morbidity over the last
waiting for surgery, and achieves similar conversion rates and
two to three decades.12 The higher level of expertise and expe-
post-operative outcomes.2–6
rience in laparoscopic surgery has equipped surgeons with more
Nevertheless, the optimal timing of SALC based on the onset
confidence in handling the potential challenges of a difficult LC
of symptoms remains controversial. Zhu et al. proposed a
for AC in patients who present beyond 72 h of symptoms.
“golden 72 hour” period as the ideal timing for SALC, beyond
The aim of this study was to establish the safety and effec-
which organized adhesions secondary to gallbladder inflamma-
tiveness of SALC in patients with AC who presented with
tion form within the Calot’s triangle, rendering surgical dissec-
different time interval from symptom onset.
tion more difficult.7 While most studies remain retrospective in

HPB 2016, -, 1–5 © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still
relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
2 HPB

Methods
A retrospective review of all patients who underwent SALC for AC
from June 2010 to June 2015 in the National University Hospital
of Singapore was performed. The diagnosis of AC in patients was
made based on the criteria outlined in the Tokyo Guidelines, with
subsequent histopathological confirmation. A total of 311 patients
who underwent SALC were included in the data analysis.
Patients with AC who underwent SALC were divided into
three groups according to the time interval between symptom
onset and surgical intervention: (i) within 3 days (E-SALC), (ii)
Results
Pre-operative and intra-operative variables and outcomes are
shown in Tables 1 and 2, respectively. There were no patients in
this cohort that required additional surgical interventions in the
form of a choledochoduodenostomy or hepaticojejunostomy.
Table 3 summarizes the post-operative outcomes in all three
groups of patients after LC.
Table 1 Patient demographics

between 4 and 7 days (M-SALC) and (iii) more than 7 days (L- E-SALC M-SALC L-SALC p-Value
SALC). This was derived via existing electronic records that n 134 135 42
accurately document patient history and clinical findings. As the Median age, 53 (24–93) 57 (21–86) 60 (19–87) 0.108
early symptoms of AC may be non-specific, symptoms were years
(range)
taken into account at their earliest onset and patients with
existing symptoms of more than 2 weeks prior to LC were Sex, n (%)
excluded from this study. Male 73 (54.5) 70 (51.9) 23 (54.8) 0.914
Broad-spectrum intravenous antibiotic therapy (intravenous Median BMI, 25 (15–43) 25 (16–45) 26 (17–41) 0.353
3rd generation cephalosporin and metronidazole) was admin- kg/m2
(range)
istered to all patients once the diagnosis of AC was made. All
Previous 7 (5.2) 16 (11.9) 5 (11.9) 0.119
surgeons involved in the operations were at least consultant abdominal
specialist surgeons, with extensive experience in hepatobiliary surgery, n
and minimally invasive surgery. The standard four-trocar tech- (%)
nique was performed for all LC, with a 10 mm port placed ASA score, n (%)
through open technique in the subumbilical/transumbilical I 65 (48.5) 55 (40.7) 11 (26.2) 0.008
region under direct vision, and three 5 mm epigastrium and II 58 (43.3) 57 (42.2) 19 (45.2)
lateral working ports inserted after the establishment of pneu- III 11 (8.2) 23 (17.0) 12 (28.6)
moperitoneum. A Kocher’s or upper midline incision was made Comorbidity, n (%)
should a conversion be required. The decision between a con-
Hypertension 55 (41.0) 54 (40) 24 (57.1) 0.133
version and the performance of a subtotal cholecystectomy was
Dyslipidemia 43 (32.1) 44 (32.6) 18 (42.9) 0.424
left to the discretion of individual consultant surgeon based on
Diabetes 37 (27.6) 32 (23.7) 11 (26.2) 0.766
their assessment of the Calot’s anatomy intra-operatively.
Patient demographics collected include age; sex; body mass Ischemic 9 (6.7) 20 (14.8) 12 (28.6) 0.001
heart
index (BMI); cardiorespiratory co-morbidities; American Soci- disease
ety of Anesthesiologists (ASA) score and previous abdominal Median symptom duration, days (range)
surgery. Intra-operative outcome parameters included duration
Prior to 1 (0–3) 2 (0–7) 5 (0–13) p < 0.001
of operation, conversion rates and injury to surrounding organ diagnosis
structures. Post-operative length of stay, morbidity and mortality After 1 (0–3) 2 (0–6) 5 (0–13) p < 0.001
were obtained and analyzed, with complications graded in diagnosis
accordance to the classification system proposed by Clavien Total 2 (1–3) 5 (4–7) 9 (8–13) p < 0.001
et al.13 Resected gallbladder specimens were sent for histopath- duration
ological examination, with the extent of inflammatory changes in Median laboratory results, unit (range)
the gallbladder wall graded accordingly.14 Upon discharge, all WBC, 14 (6–34) 13 (4–23) 13 (6–28) 0.057
patients were followed up for a minimum duration of 90 days n × 109L
and relevant clinical information would be documented and CRP, mg/L 102 (6–400) 105 (5–396) 156 (7–446) 0.286
retrieved via the electronic medical record system. Glucose, 8 (5–29) 8 (3–22) 8 (5–20) 0.765
Categorical variables were compared using the Pearson’s Chi- mmol/L
square test, while continuous variables were compared using the Amylase, 73 (30–225) 74 (30–306) 74 (30–314) 0.745
Kruskal–Wallis H Test. Statistical analysis was performed using u/mL

the SPSS statistical package (v 19.0; IBM Corporation, Armonk, Abbreviations: ASA, American Society of Anesthesiologists; BMI, body
NY, USA), and all p-values reported were two-sided, with p- mass index; TG, Tokyo guidelines; WBC, white blood count; CRP, C-
values of <0.05 considered statistically significant. reactive protein.

HPB 2016, -, 1–5 © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still
relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
HPB 3

Table 2 Operative parameters Discussion

E-SALC M-SALC L-SALC p-Value
While the use of minimally invasive surgery has gained popu-
Median operative 103 100 107 0.424 larity worldwide across surgical disciplines, laparoscopic chole-
time, minutes (35–209) (24–264) (46–220)
(range) cystectomy (LC) was once considered a relative contraindication
Conversion, n (%) 11 (8.2) 13 (9.6) 9 (21.4) 0.048
in the presence of AC in view of increased morbidity and con-
version rates.15–18 However, recent trials have shown SALC to be
Intra-operative 0.701
severity, n (%) superior in cost effectiveness and patient quality of life as
Edematous 75 (56.0) 70 (51.9) 20 (47.6) compared to DLC.1 As a result, SALC has gradually been estab-
lished as the standard of care in the management of AC patients.
Mucocele 3 (2.2) 4 (3.0) 3 (7.1)
Nonetheless, the criteria for offering SALC to patients with
Gangrenous 36 (26.9) 36 (26.7) 13 (31.0)
respect to duration of symptoms remain relatively ambiguous in
Empyema 20 (15.0) 25 (18.5) 6 (14.3)
existing literature. A Cochrane review outlined the benefits of
Other intra-operative procedures, n (%) SALC for AC patients with seven days of symptoms presenta-
IOC 12 (9.0) 17 (12.6) 8 (19.0) 0.204 tion,1 while various prospective studies showed similar results for
CBDE 2 (1.5) 1 (0.7) 1 (2.4) 0.656 same admission cholecystectomies performed within 24–96 h.19
Intra-operative 0 2 (1.5) 0 0.704 More specifically, prevailing studies that specifically analyzed
morbidity, n (%) outcomes between different intervals of symptom duration prior
Bile duct injury 0 0 0 to SALC remain largely retrospective, with varied recommen-
Bowel injury 0 2 (1.5) 0 dations in defining an optimal time period of symptoms beyond
Others 0 0 0 which patient should be considered for DLC.2–6
Intra-operative 0 0 0 NA In recent years, several studies have proposed SALC to be
mortality, n (%) performed within the “golden 72 hours” of symptom duration.7
The authors argued that operative difficulty would increase
Abbreviations: IOC, intra-operative cholangiogram; CBDE, common bile
duct exploration. thereafter due to severe inflammatory adhesions, resulting in an
increased risk of conversion and bile duct injury. Indeed,
Gonzalez-Rodriguez et al. reported a significantly lower con-
version rate of 7.8% vs 18.4% in patients who underwent SALC
before and after 72 h of symptom onset respectively, while Zhu
Table 3 Post-operative outcomes
et al. found longer operative times in the latter group.7,20
E-SALC M-SALC L-SALC p-Value Despite the ostensible benefits, the feasibility of performing
Median total length of 4 (2–33) 2 (2–23) 7 (2–49) p < 0.001 SALC within 72 h is often questioned due to a multitude of
stay, days (range)
factors.21 This is demonstrated in the current study as only
Median post-operative 2 (1–33) 2 (1–20) 2 (1–17) 0.157 43.1% of AC patients managed to undergo SALC within 72 h of
length of stay, days
(range) their reported symptom onset. Firstly, the non-specific nature of
Grade of 0.695 initial symptoms and possible attempts by patients to self-
complications, n (%) medicate with may result in the late recognition of the condi-
I 1 (0.7) 2 (1.5) 0 (0.0) tion. Secondly, the hold-up in time to diagnose AC could occur
II 13 (9.7) 13 (9.6) 6 (14.3) after admission, when AC might not be the initial primary
III 2 (1.5) 0 (0.0) 0 (0.0)
diagnosis due to its diverse presenting symptoms. The time taken
to obtain definitive radiological investigations is also often a rate-
IV 0 (0.0) 0 (0.0) 0 (0.0)
limiting step in the diagnosis of AC. In addition, a substantial
V 0 (0.0) 1 (0.7) 0 (0.0)
group of patients with significant co-morbidities would require
Overall 16 (11.9) 16 (11.9) 6 (14.3)
time for adequate pre-operative assessment and optimization.
Histopathological 0.456 The aforementioned factors are apparent in the current study,
grade,a n (%)
which showed a longer duration of symptoms prior to and after
Grade 1 42 (31.3) 53 (39.3) 18 (42.9)
patients are diagnosed with AC in the L-SALC group. Additional
Grade 2 32 (23.9) 30 (22.2) 11 (26.2) measures such as patient education in the primary healthcare
Grade 3 60 (44.8) 52 (38.5) 13 (31.0) setting, expedition of relevant patients to secondary care and
a
Histopathological grade of gallbladder specimen: Grade 1 (erosive/
improvement in diagnostic and intervention processes can be
ulcerous inflammation); Grade 2 (phlegmonous inflammation); Grade 3 attempted and evaluated to shorten symptom duration prior to
(gangrenous inflammation). SALC.

HPB 2016, -, 1–5 © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still
relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
4 HPB
In assessing the operative difficulty of SALC between different
time intervals of symptom duration, the current study revealed a
significant difference in the conversion rates between E-SALC,
M-SALC and L-SALC, with reported figures of 8%, 10% and
21%, respectively. Hence, the risk of conversion in SALC in-
creases considerably in patients with more than a week duration
of symptoms. Although these results are seemingly different
from previous studies supporting E-SALC,2–6 it is postulated that
the higher conversion rates seen with other studies in patients
with more than 72 h of symptoms can partially be contributed by
a sub-group of patients that presented with symptoms beyond
one week. Furthermore, the increased levels of levels of expertise
in laparoscopic surgery and the emerging technique of subtotal
cholecystectomy could also have potentially mitigated the chal-
lenges faced previously while performing SALC, substantiated by
the similar operative times seen across all three groups in the
current series.
A reduction in hospital length of stay and its resultant
improvement in cost effectiveness remains a major aspect in
supporting the use of SALC over DLC. Various studies have
shown that SALC results in hospitalization four days shorter than
that of DLC.1,22 While total length of hospital stay was increased
in patients with longer symptom duration, this was an expected
result as L-SALC patients also had higher ASA scores, suggesting a
need for workup and optimization of existing co-morbidities
prior to surgery. Despite so, post-operative length of stay
remained similar across all groups between three to four days,
which was consistent with existing literature. Apart from a shorter
hospitalization, patients with SALC also enjoy an improvement in
quality of life through faster return to work whilst avoiding any
gallstone-related morbidity while awaiting elective surgery, for
which studies have shown up to 18% of DLC patients require
emergency LC due to non-resolution of symptoms.1
The retrospective nature of this study and its resultant po-
tential for selection bias is a limitation of this project, but there
was no significant difference shown in important patient char-
acteristics such as age, gender, previous abdominal surgery and
body mass index between the three groups. This negates the
presence of confounders that can inadvertently affect the various
outcomes measures analyzed in this study. The presence of recall
bias can also be a limitation while assessing patient symptom-
atology. However, majority of patients in the current study with a
suspected diagnosis of AC were referred immediately to the
hepatopancreaticobiliary service allowing for better standardi-
zation in patient evaluation.
Conclusion
SALC can be safely performed in AC patients presenting with less
than a week of symptoms, and should be advocated in centers
with MIS expertise and adequate resources in accommodating a
higher emergency operating theater patient load. This would
allow for more patients to be treated with SALC, and reap its
HPB 2016, -, 1–5 © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still
relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006
purported benefits. Further prospective studies comparing DLC
to SALC in patients with different interval of symptom duration
should be conducted to better define management pathways in
the treatment of AC.
Conflict of interest and disclosure
None declared.
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HPB 2016, -, 1–5 © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Tan JKH, et al., Same admission laparoscopic cholecystectomy for acute cholecystitis: is the “golden 72 hours” rule still
relevant?, HPB (2016), http://dx.doi.org/10.1016/j.hpb.2016.10.006