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Asian Journal of Surgery (2018) 41, 47e54

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ORIGINAL ARTICLE

Outcomes of early versus delayed


cholecystectomy in patients with mild to
moderate acute biliary pancreatitis: A
randomized prospective study
Shir Li Jee a,*, Razman Jarmin b, Kin Foong Lim a,
Krishnan Raman a

a
HepatobiliaryePancreatic Surgery Unit, Selayang Hospital, Lebuhraya Selayang-Kepong, 68100 Batu
Caves, Selangor Darul Ehsan, Malaysia
b
HepatobiliaryePancreatic and General Surgery Unit, National University of Malaysia, 43600 UKM,
Bangi, Selangor Darul Ehsan, Malaysia

Received 18 April 2016; received in revised form 26 May 2016; accepted 30 May 2016
Available online 13 August 2016

KEYWORDS Abstract Background: In patients with acute biliary pancreatitis (ABP), cholecystectomy is
biliary pancreatitis; mandatory to prevent further biliary events, but the precise timing of cholecystectomy for
cholecystectomy; mild to moderate disease remain a subject of ongoing debate. The aim of this study is to assess
recurrent biliary the outcomes of early versus delayed cholecystectomy. We hypothesize that early cholecystec-
events; tomy as compared to delayed cholecystectomy reduces recurrent biliary events without a high-
ERCP er peri-operative complication rate.
Methods: Patients with mild to moderate ABP were prospectively randomized to either an
early cholecystectomy versus a delayed cholecystectomy group. Recurrent biliary events,
peri-operative complications, conversion rate, length of surgery and total hospital length of
stay between the two groups were evaluated.
Results: A total of 72 patients were enrolled at a single public hospital. Of them, 38 were ran-
domized to the early group and 34 patients to the delayed group. There were no differences
regarding peri-operative complications (7.78% vs 11.76%; p Z 0.700), conversion rate to open
surgery (10.53% vs 11.76%; p Z 1.000) and duration of surgery performed (80 vs 85 minutes,
p Z 0.752). Nevertheless, a greater rate of recurrent biliary events was found in the delayed
group (44.12% vs 0%; p  0.0001) and the hospital length of stay was longer in the delayed
group (9 vs 8 days, p Z 0.002).

Conflicts of interest: All the authors whose names are listed above certify that they have no affiliations with or involvement in any
organization or entity with any financial interest, or nonfinancial interest in the subject matter.
* Corresponding author. B20805, Royal Domain (Sri Putramas II), Jalan Putramas 1, Off Jalan Kuching, 51200 Kuala Lumpur, Malaysia.
E-mail address: jeeshirli@hotmail.com (S.L. Jee).

http://dx.doi.org/10.1016/j.asjsur.2016.07.010
1015-9584/ª 2016 Asian Surgical Association and Taiwan Robotic Surgical Association. Publishing services by Elsevier B.V. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
48 S.L. Jee et al.

Conclusion: In mild to moderate ABP, early laparoscopic cholecystectomy reduces the risk of
recurrent biliary events without an increase in operative difficulty or perioperative morbidity.
ª 2016 Asian Surgical Association and Taiwan Robotic Surgical Association. Publishing services
by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction patients who did not have cholecystectomy performed


during the index admission, 13.4% developed recurrent
Gallstone disease is the leading cause of acute pancreatitis ABP while awaiting cholecystectomy. A total of 12.5% of
in developed nations, accounting for up to 75% of cases.1 In recurrences occurred within 1 week, 31.3% occurred
Malaysia, a retrospective study done over a period of 7 within 2 weeks, and one-half of them within 4 weeks
years showed that in nearly one-half of the patients (45.1%) after discharge.14 This finding is crucial as recurrent at-
admitted for acute pancreatitis, the etiology was biliary tacks of biliary pancreatitis can be severe and life
calculi, followed by alcohol intake (19.7%).2 threatening.
After biliary pancreatitis, patients may experience a Despite these guidelines and literatures, cholecystec-
recurrent episode of biliary pancreatitis, common bile duct tomy during the same admission is not commonly prac-
(CBD) obstruction, cholangitis, or biliary colics.3,4 Chole- ticed. A recent study of over 25,000 patients acutely
cystectomy and clearance of stones from the biliary tree admitted to hospitals in England with gallstone-related
remain the mainstay of treatment to prevent recurrent disease showed that only 14.7% underwent cholecystec-
biliary events.1,5 tomy during the same admission.15 Another study in the US
Most cases of acute biliary pancreatitis (ABP) are mild showed that only half of the patients admitted for ABP had
and self limiting; however, 10e20% of patients develop cholecystectomy done during the same admission. Pa-
severe pancreatitis, which is associated with high morbidity tients admitted to hospitals with smaller annual volumes
and mortality.5 The timing of cholecystectomy in patients of cholecystectomy or higher annual volumes of acute
with clinically severe pancreatitis, with local complications pancreatitis admissions were less likely to undergo cho-
such as pancreatic necrosis and organ failure, is deliber- lecystectomy during the initial hospitalization for ABP.16 A
ately delayed until local complications have resolved, nationwide study in the Netherlands demonstrated that
typically after approximately 6 weeks.6 For mild to mod- three-quarters of the patients admitted with mild biliary
erate ABP, international guidelines recommend early chol- pancreatitis underwent cholecystectomy a median of 6
ecystectomy.1,3e5,7,8 However, the definition of “early” weeks after discharge.13 The majority of specialists
varies amongst the guidelines. The International Associa- perform an interval cholecystectomy due to uncertainty
tion of Pancreatology (IAP) recommends that all patients regarding the efficacy and safety of an early cholecys-
with gallstone pancreatitis should undergo cholecystec- tectomy. The lack of evidence from prospective random-
tomy as soon as the patient has recovered from the at- ized controlled trials may contribute to that. Limitations
tacks,1 whereas the British Society of Gastroenterology to hospital resources, such as access to surgeons, oper-
recommend cholecystectomy within the same hospital ating room time, and postoperative intensive unit beds,
admission or up to 2 weeks after discharge.4 The American may also contribute to noncompliance to recommenda-
Gastroenterological Association guidelines suggest that tions for early cholecystectomy.
cholecystectomy should be performed as soon as possible Other definitive biliary interventions such as endoscopic
and in no case beyond 2e4 weeks after discharge,3 whereas retrograde cholangiopancreatography (ERCP) with endo-
the American College of Gastroenterology recommend scopic sphincterotomy (ES) can also independently reduce
cholecystectomy within index admission.8 The variation in rates of recurrence of ABP but may result in higher rates of
the recommended timing of cholecystectomy between biliary complications when compared with cholecystec-
these guidelines arose from differing views and adopted tomy.17 ERCP and ES alone without cholecystectomy as
practices, and more importantly, is due to the lack of evi- definitive therapy for ABP still remain controversial. ERCP
dence from prospective randomized controlled trials with its higher incidence of postprocedure pancreatitis
addressing the timing and safety of early operative resulted in longer hospital length of stay when compared
intervention. with laparoscopic cholecystectomy and intraoperative
Several nonrandomized studies published recently cholangiogram (IOC) even when common bile duct explo-
favor cholecystectomy during the same index admission ration was performed.18 Nevertheless, ES can be used as an
for ABP.9e13 The rationale for cholecystectomy during the accepted definitive treatment in elderly patients who have
same hospitalization, compared with interval cholecys- multiple comorbid conditions and are not fit for surgery to
tectomy, is that it leads to a reduction in the frequency prevent recurrence of pancreatitis.
of recurrent biliary events (e.g., recurrent biliary To date, there is only one published prospective ran-
pancreatitis, acute cholecystitis, symptomatic chol- domized controlled trial in the US looking into the timing
edocholithiasis, and biliary colic) in these patients. Ito of cholecystectomy after ABP in 50 patients.19 In this
et al14 noted that there is an increased risk of recurrence study, there was no comparison group randomized to un-
within 2e4 weeks after discharge. In the group of dergo cholecystectomy electively after discharge.
Timing of cholecystectomy in pancreatitis 49

Moreover, this trial did not assess the efficacy of early 2.4. Inclusion criteria
cholecystectomy on long term outcomes such as recurrent
biliary events. In this study, we performed a comparative All patients aged 18 years and older who were admitted to
study of the outcomes of patients with early (cholecys- Selayang Hospital with mild to moderate ABP and con-
tectomy done within index admission) versus delayed sented to participate in this study were included.
cholecystectomy (cholecystectomy done on an elective A participant was diagnosed as having acute pancreatitis
basis after discharge, at w 6 weeks), concentrating only if they had at least two of the three following features20:
on patients with mild to moderate acute biliary pancrea- (1) clinical signs of pancreatitis, e.g., upper abdominal
titis. We hypothesize that early cholecystectomy pain, nausea, vomiting, and epigastric tenderness; (2) an
compared with delayed cholecystectomy in patients with elevated serum amylase level of at least thrice the upper
mild to moderate ABP reduces recurrent biliary events limit of normal; and (3) characteristic findings of acute
without a higher perioperative complication rate. pancreatitis on abdominal imaging. Biliary pancreatitis was
defined by the presence of the following: (1) confirmatory
diagnosis of gallstones and/or sludge on radiological imag-
2. Research setting and methodology ing; and (2) absence of ethanol abuse (males > 3 units/d,
female > 2 units/d). The classification of mild to moderate
pancreatitis was defined by the presence of the following20:
2.1. Study setting (1) no pancreatic necrosis and/or peripancreatic collec-
tions; (2) no persistent (>48 hours) organ failure; (3) clin-
This study was carried out in Selayang Hospital, a public ical stability with hospital admission not requiring intensive
hospital in the state of Selangor, Malaysia, over a period of care unit (ICU) or high dependency unit (HDU) care; and (4)
1 year (November 2013 to November 2014). absence of concomitant acute cholangitis.

2.2. Study design and randomization 2.5. Exclusion criteria

Patients were excluded if they had any of the following: (1)


This is an open-label, prospective randomized controlled
severe pancreatitis (as defined by the presence of 3 or more
study. Patients diagnosed to have mild to moderate ABP
of Ranson’s or Imrie criteria on admission); (2) admission to
who meet the inclusion criteria and gave informed consent
ICU or HDU; (3) suspected concomitant acute cholangitis;
to participate in the study were prospectively randomized
(4) severe preexisting medical comorbidity contraindicating
to either an early or delayed cholecystectomy group.
cholecystectomy (as determined by the primary physician);
Concealing the allocation for investigators or study par-
(5) pregnancy; and (6) prior gastric bypass surgery
ticipants is unfeasible due to the nature of this study,
(rendering ERCP difficult).
because study participants need to be scheduled for an
early or delayed cholecystectomy. Random assignment was
performed by drawing a sealed, unlabeled, unordered 2.6. Ethical consideration
envelope from a container by an independent party
immediately after informed consent was obtained. In pa- Approval was obtained from the National University of
tients randomized to the early group, cholecystectomy Malaysia Medical Centre Clinical Research Ethics Commit-
with IOC was performed within the index admission when tee and Medical Research Ethics Committee, Ministry of
patients no longer required opioid analgesics, could Health prior to initiating this study. Permission for data
tolerate a normal oral diet and had serum C-reactive collection and analysis was obtained from the relevant
protein concentration < 100 mg/L. In the delayed group, authorities in Selayang Hospital with regards to the
interval cholecystectomy with IOC was performed on an reviewing of patients’ medical records and reports. All
elective basis after hospital discharge from the index patient information sheets were kept privy throughout the
admission, at approximately 6 weeks after the pancreatitis study.
episode. Cholecystectomy was performed as a laparo-
scopic procedure unless contraindicated, in which case, 2.7. Data collection
open cholecystectomy would be performed. All the oper-
ations were performed by a single consultant hepatobiliary
Data collection was commenced in Selayang Hospital after
surgeon. All patients received appropriate perioperative
the study was approved. Preoperative, operative, and
antibiotic prophylaxis.
postoperative data were prospectively collected for each
patient participating in the study.
2.3. Sample size calculation
2.8. Data analysis
To demonstrate a reduction of recurrent biliary events with
power of 80% and two sided test of 5%, 55 patients will have Data entry utilizing codes were performed using the SPSS
to be included in each group (PS Calculations, version 2.1.3; software version 16.0 (Chicago, IL, United States of
Vanderbilt University, Nashville, TN, USA). With an esti- America) licensed to National University of Malaysia. Com-
mated a drop-out rate of 10%, a sample size of 60 in each puter assisted analysis was carried out at the end of the
group is needed. study. Results were expressed as means with 95%
50 S.L. Jee et al.

confidence intervals (CI) or medians with interquartile which was incidentally found on IOC during cholecystec-
ranges (IQRs) for continuous variables and ManneWhitney U tomy (Table 1).
tests were performed to assess for significant differences
between two groups. Frequencies were presented for cat-
egorical variables and Fischer’s exact test or chi-square 3.2. Perioperative outcomes
tests were used as appropriate.
Perioperative outcomes are shown in Table 2. All 72 pa-
tients underwent laparoscopic cholecystectomy. In 64 pa-
2.9. Termination of study
tients (89.47% in the early group and 88.24% in the delayed
group), laparoscopic cholecystectomy was completed suc-
An interim analysis was performed midway through the
cessfully. Conversion to open surgery was necessary in eight
study which revealed a significant difference in the rate of
patients (4 in the early group and 4 in the delayed group;
recurrent biliary events and that which required hospital
p Z 0.99). These included five patients who were found to
readmissions in the delayed cholecystectomy group
have severe inflammatory adhesions that precluded safe
compared with the early cholecystectomy group. After
dissection of the Calot’s triangle, and three patients who
discussion with the supervising and ethics committee, a
had impacted CBD stones discovered on the IOC and
decision was made to terminate the study. At the time of
required open surgical exploration. Among the latter three
termination, a total of 72 patients had completed partici-
patients, two had undergone precholecystectomy ERCP
pation in the study.
during which stones were removed and an occlusion chol-
angiogram had shown complete clearance. The remaining
3. Results one patient was not suspected preoperatively to have CBD
stones and did not undergo preoperative ERCP.
There is no difference between the two groups in the
3.1. Demographic pattern of patients duration of surgery (median of 80 minutes in the early
group and 85 minutes in the delayed group, p Z 0.752).
A total of 82 patients who were diagnosed with a primary There is also no statistically significant difference in the
episode of mild to moderate ABP and had fulfilled the complication rates between the two groups. There was one
criteria of the study were recruited. The patients were intraoperative complication which occurred in the delayed
randomized into two groups as mentioned in the method- group; this was an injury to duodenal serosa during mobili-
ology above. Ten patients subsequently withdrew from the zation which was recognized and repaired immediately during
study due to reasons which included opting for alternative surgery. This case was among the five patients who required
medicine therapy, change of mind on undergoing surgery,
and deciding to undergo surgery in another institution. A
total of 72 patients were enrolled in the final analysis of this
study. Table 1 Patient demographics in relation to timing of
There were 31 male (43.06%) and 41 female (56.94%) cholecystectomy.
patients in this study. The age range was from 18 to 75 to Early group Delayed group p*
with a mean of 41.93 years. In the study population, the (n Z 38) (n Z 34)
majority of patients were Malays (55.56%), followed by Patients
foreigners (19.44%), Chinese (18.06%), and Indians (6.94%). Age (y), median 42.5 42.5 0.977
This ethnic distribution reflected the ethnic composition of and IQR (29.75e52) (30.75e54.25)
the general Malaysian population of patients seeking Sex 0.435
treatment in the public health system. Male 18 (47.37%) 13 (38.24%)
Thirty eight patients were randomized into the early Female 20 (52.63%) 21 (61.76%)
group and 34 patients into the delayed group. There is no Race 0.353
significant difference between the two groups in age, Malay 24 (63.16%) 16 (47.06%)
gender, and ethnic demographics (Table 1). Chinese 6 (15.79%) 7 (20.59%)
The median time interval from diagnosis of ABP to cho- Indian 1 (2.63%) 4 (11.76%)
lecystectomy in the early group was 6 days whereas the Foreigner 7 (18.42%) 7 (20.59%)
median time in the delayed group was 44 days (Table 1). Procedures
Nineteen patients (50%) in the early group and 15 pa- ERCP 19 (50%) 17 (50%) > 0.99
tients (44.12%) in the delayed group underwent an ERCP
Preop 19 15 0.644
prior to cholecystectomy due to a strong suspicion of CBD Postop 0 2 0.220
stones, based on laboratory biochemical parameters and Time to 6 (5e9) 44 (36e56) a
imaging findings. Of these 34 patients, 33 patients under-
cholecystectomy
went ES and stone extraction. The remaining patient did
(d), median,
not have evidence of CBD stone on ERCP. There is no sig- and IQR
nificant difference between the two groups in reference to
the patients undergoing precholecystectomy ERCP (Table * p value < 0.05 was classed as significant.
ERCP Z endoscopic retrograde cholangiopancreatography;
1).
IQR Z interquartile range.
Two patients in the delayed group underwent ERCP a
Not performed.
postcholecystectomy for removal of a small CBD stone
Timing of cholecystectomy in pancreatitis 51

Table 2 Perioperative outcomes in relation to timing of Table 3 Recurrent biliary events in 34 candidates for
cholecystectomy. delayed cholecystectomy.
Early group Delayed p* No. of No. of
(n Z 38) group patients readmissions
(n Z 34) No. of recurrent biliary events 15 (44.12%) 8 (53.33%)
Conversion to open 4 (10.53%) 4 (11.76%) > 0.99 Biliary colic 10 (29.41%) 3 (20.00%)
Duration of 80 (60e95) 85 (60e120) 0.752 Acute cholecystitis 3 (8.82%) 3 (20.00%)
surgery (min), Recurrent biliary pancreatitis 2 (5.88%) 2 (13.33%)
median, IQR Time of onset of recurrent
Overall 3 (7.89%) 4 (11.76%) 0.700 biliary events after discharge
complications Within 2 weeks 4 (26.67%)
Perioperative 0 1 (2.94%) 0.472 Within 4 weeks 11 (73.33%)
complication After 4 weeks 4 (26.67%)
Postoperative 3 (7.89%) 3 (8.82%) > 0.99 Time after discharge (d), 20 (12e29)
complication median, IQR
a
Mortality 0 0 IQR Z interquartile range.
Total LOS (d), 8 (6e10) 9 (8e11) 0.002
median, IQR
* p values < 0.05 were classed as significant and are highlighted 3.4. Role of ES
in bold.
IQR Z interquartile range; LOS Z length of stay.
a
Not performed.
ES was performed in 33 (45.83%) of 72 patients. Stones or
sludge were found in the CBD during ERCP in all 33 patients.
All stones and sludge were cleared before cholecystectomy.
There is no statistically significant difference in recurrent
conversion to open surgery due to dense adhesions and diffi-
biliary events in patients who had ES performed compared
cult mobilization. The overall operative mortality was 0%.
with patients who did not have ES performed (8 vs. 7;
Postoperative complications occurred in six out of 72
p Z 0.569). The rates of recurrent biliary events in patients
patients (3 in the early group and 3 in the delayed group).
who did or did not undergo ES before cholecystectomy are
Five out of six patients had surgical site infections which
shown in Table 4.
were treated with daily outpatient dressing. One patient in
the delayed group had an episode of pancreatitis post
operatively. The patient was readmitted 2 days after
discharge with mild pancreatitis and was treated conser-
4. Discussion
vatively and warded for 3 days.
The total length of stay (LOS) (which includes the index The timing of cholecystectomy in patients with ABP has
admission plus admission for precholecystectomy re- been a contentious issue for a long time. It is an established
currences plus admission for cholecystectomy) is longer in practice that patients admitted for severe ABP have their
the delayed group compared with the early group. In the cholecystectomy delayed until local complications have
delayed group, median total LOS is 9 days (interquartile resolved, typically after some 6 weeks.6 Sanjay et al21
range [IQR] Z 8e11) whereas it is 8 days (IQR Z 6e10) in concluded that ES and interval cholecystectomy in severe
the early group (p Z 0.001). ABP is associated with minimal morbidity and readmission
rates. Several studies published are relevant to determining
the optimal timing of cholecystectomy in patients with mild
3.3. Recurrent biliary events ABP but randomized prospective data are limited. As a
result, available guidelines vary with respect to recom-
In the 38 patients who underwent cholecystectomy during mendations on the ideal timing of cholecystectomy.1,3e5,7,8
the index admission, there was no recurrent biliary event in Indeed, there is no consensus on whether or not patients
the short interval between recovery from pancreatitis and
cholecystectomy. Fifteen patients (44.12%) in the delayed
group had gallstone-related symptoms prior to cholecys-
Table 4 Recurrent biliary events in patients who did or
tectomy. The difference between the two groups is signif-
did not undergo ES before cholecystectomy.
icant (0% vs. 44.12%, p < 0.0001). Eight of the 15 patients
(53.33%) required hospital readmission due to severity of ES (n Z 33) No ES (n Z 39) p*
the biliary events. Ten patients (29.41%) had biliary colic, Biliary events 8 (24.24%) 7 (17.95%) 0.569
three patients (8.82%) developed acute cholecystitis, and Recurrent 1 (3.03%) 1 (2.56%) > 0.99
two patients (5.88%) had recurrent biliary pancreatitis. No pancreatitis
incidence of cholangitis occurred in this study. The median Cholecystitis 2 (6.06%) 1 (2.56%) 0.590
time between discharge and readmission is 20 (12e29) Biliary colic 5 (15.15%) 5 (12.82%) > 0.99
days. Eleven admissions (73.33%) occurred within 4 weeks
* p values < 0.05 were classed as significant.
after discharge. Biliary events requiring readmission before
ES Z endoscopic sphincterotomy.
cholecystectomy are summarized in Table 3.
52 S.L. Jee et al.

who suffer an episode of ABP can be safely discharged prior early laparoscopic cholecystectomy (within 48 hours of
to undergoing cholecystectomy. admission) with control laparoscopic cholecystectomy
For several decades surgeons have legitimated the choice (performed after resolution of symptoms and normalizing
for interval cholecystectomy on the belief that cholecys- trend of laboratory enzymes). There was no statistically
tectomy during index admission would be associated with significant difference in the need for conversion to open
difficult dissection due to edema caused by pancreatitis, surgery or in perioperative complication rates between two
which could lead to more surgical complications and unnec- groups. However, early cholecystectomy was associated
essary conversion. However, recent studies including three with a significantly shorter length of hospital stay, 3 days
meta analyses and one cohort study showed that delaying compared with 4 days in the control group (p Z 0.0016).19
cholecystectomy has no advantage regarding intraoperative This approach was supported by Rosing et al10 who insti-
complications.12,22e24 In this study, early cholecystectomy tuted a practice of early cholecystectomy in a prospective
did not lead to an increase in overall complication rate, study of 43 patients. The conclusions of these studies are
overall conversion rate, duration of surgery, and mortality consistent with the present study which reports early cho-
rate. Below is a table comparing complication rates in our lecystectomy results in a significantly reduced length of
study to those in the literature (Table 5). hospital stay with no increase in complications or mortality.
The rate of conversion to open surgery is notably higher The role and timing of ERCP for ABP is also controversial
in this study compared with those in other series. A possible and is another contributor to delaying cholecystectomy. In
reason may be that the patients with gallstone disease in a meta-analysis of randomized controlled trials, Moretti
Malaysia tend to have a higher incidence of chronic chole- et al29 demonstrated that early ERCP reduces pancreatitis-
cystitis and impacted stones which lead to a higher fre- related complication in patients with predicted severe
quency of adhesions and ‘difficult gallbladder’, and pancreatitis but has no advantage in predicted mild
therefore, the higher rate of conversion. pancreatitis compared with conservative management. In a
Several, mostly retrospective, studies have suggested prospective randomized study by Chang et al,30 patients
that there is a substantial risk of recurrent biliary events with mild to moderate gallstone pancreatitis without
after discharge from hospital following an episode of ABP cholangitis were randomized to preoperative ERCP versus
and before interval cholecystectomy. The reported inci- post operative ERCP if CBD stones were seen on IOC. There
dence of recurrent biliary events in these literatures is was no difference in complication rate, but length of stay
between 9% and 60%.11e14,22,25e28 and costs were significantly less in the postoperative ERCP
Our study demonstrated a significant difference in group. According to the American Society for Gastrointes-
recurrent biliary events (44% vs. 0%) and this rate was tinal Endoscopy guidelines, there is no role for early ERCP in
comparable to that reported in the literatures. A total of 6% the evaluation and management of patients with mild acute
of patients in our study had relapse of mild ABP. One pa- pancreatitis in the absence of clear evidence of a retained
tient had recurrent CBD stone and the other patient prob- stone.3 In this current study, there is no difference in the
ably had migration of biliary sludge. An incomplete or use of ERCP between the early and delayed groups. In 38
partially reoccluded sphincterotomy may also have a role in patients who did not have preop ERCP done, only three
the recurrence of symptoms. patients demonstrated CBD stone on IOC. All three patients
Recurrent biliary events in our study are also clinically were treated successfully; one with intraoperative CBD
significant in that > 50% of patients with recurrent biliary exploration and another two patients with postoperative
events had symptoms severe enough to warrant admission ERCP and stone extraction. Therefore our current approach
to hospital. A recent investigation by Ito et al suggested for mild to moderate ABP is to limit preoperative ERCP to
that an interval of 2 weeks between discharge and chole- patients with cholangitis, a strong suspicion of CBD stones
cystectomy might be too long as 31% of recurrences or apparent cholestasis, which would be done within same
occurred within 2 weeks after discharge.14 In accordance index admission.
with the literature, our study demonstrated a recurrence ERCP and ES apgallstones pancreatitis, and this has
rate of 27% within 2 weeks after discharge. increasingly been used in elderly and frail people.17,27,31e33
In this study, patients who underwent delayed chole- Bignell et al31 demonstrated that 94% of patient treated
cystectomy had longer overall LOS than patients who un- with ERCP and ES alone had no recurrence of pancreatitis in
derwent cholecystectomy during index admission because a large retrospective study with a long follow-up (up to 10
24% of them required readmission for recurrent biliary years). Although these studies showed that ES alone is
events. These readmissions could have been prevented if effective in reducing recurrent pancreatitis, patient who
cholecystectomy had been performed at index admission. undergo only ES are at further risk of complications related
In a randomized controlled trial, Aboulian et al19 compared to the gallbladder. Due to the high risk of biliary

Table 5 Results of a review of complications in the literature.


Author and year No. of Complications Complications Conversion Conversion
patients (early) (delayed) (early) (delayed)
Van Baal et al, 2012 12 998 4% 6% 9% 6%
26
Randial Perez et al, 2014 636 4.83% 4.42% d d
Johnstone et al, 2014 25 523 13% 9% 2% 8%
Current study 72 7.89% 8.82% 10.53% 11.76%
Timing of cholecystectomy in pancreatitis 53

complications (ranging from 10% to 23%),27,31-33 it was 2. Nadesan S, Qureshi A, Daud A, Ahmad H. Characteristics of
suggested that ERCP and ES should be used as an alterna- acute pancreatitis in University Kebangsaan Malaysia. Med J
tive to cholecystectomy in treatment of ABP in high risk Malaysia. 1999;54(2):235e241.
surgical patients and elderly. However, for patients who 3. Forsmark CE, Baillie J. AGA Institute technical review on acute
pancreatitis. Gastroenterology. 2007;132(5):2022e2044.
are deemed fit for surgery, current literatures recommend
4. UK guidelines for the management of acute pancreatitis. Gut.
ES followed by cholecystectomy in the treatment of 2005;54(Suppl 3:iii):1e9.
ABP.33e35 In the current study, ES did not appear to have a 5. Banks PA, Freeman ML. Practice guidelines in acute pancrea-
protective role in recurrent ABP as well as other biliary titis. Am J Gastroenterol. 2006;101(10):2379e2400.
complications before cholecystectomy, though this did not 6. Nealon WH, Bawduniak J, Walser EM. Appropriate timing of
reach statistical significance (Table 4). It may perhaps be cholecystectomy in patients who present with moderate to
noted that the majority of recurrent biliary events in the severe gallstone-associated acute pancreatitis with peri-
study were nonpancreatitis conditions, namely biliary colic pancreatic fluid collections. Ann Surg. 2004;239(6):741e749.
and cholecystitis, which are typically not reduced by ES. discussion 49e51.
Postcholecystectomy pancreatitis has been shown to 7. Toouli J, Brooke-Smith M, Bassi C, et al. Guidelines for the
management of acute pancreatitis. J Gastroenterol Hepatol.
occur and indeed, there have been reports of pancreatitis
2002:17. Suppl:S15-39.
recurring after cholecystectomy. These may be due to 8. Tennet S, Bailie J, DeWitt J, Vege SS. American College of
retained CBD stones or sludge. In this study, there was a Gastroenterology Guideline : management of acute pancreatitis.
patient who had postcholecystectomy pancreatitis. Though Am J Gastroenterol. 2013. http://dx.doi.org/10.1038/
the IOC did not show evidence of CBD stone, a possible ajg.2013.218.
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not have been picked up. Nevertheless, pancreatitis cystectomy and ERCP are associated with reduced read-
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A larger sample size in this study would have been more
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In conclusion, the findings of this study of patients with
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mild to moderate ABP demonstrate that laparoscopic cho- pancreatitis: do the data support current guidelines? J Gas-
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Appendix A. Supplementary data 19. Aboulian A, Chan T, Yaghoubian A, et al. Early cholecystectomy
safely decreases hospital stay in patients with mild gallstone
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online at http://dx.doi.org/10.1016/j.asjsur.2016.07.010. 251(4):615e619.
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