Long-Term Outcome of Patients with Acute CholecystitisReceiving Antibiotic Treatment: A Retrospective Cohort Study

Chih-Hung Wang • Hao-Chang Chou •

Kao-Lang Liu • Wan-Ching Lien • Hsiu-Po Wang •

Yao-Ming Wu

Published online: 1 November 2013

� Societe Internationale de Chirurgie 2013

Abstract

Background Few studies have followed patients who

received antibiotic treatment for acute cholecystitis (AC).

The present retrospective study investigated recurrence rates

of AC and analyzed factors associated with recurrence after

antibiotic treatment in adult AC patients.

Methods We analyzed patients treated with antibiotics for

AC between October 1, 2004, and November 30, 2010.

A Cox proportional hazards model was used to identify

factors associated with early recurrence. Generalized

additive models were applied to detect the nonlinear effects

of continuous covariates.

Results The study included 226 patients (mean age:

62.2 years; 144 men [63.7 %]). The average duration of

parenteral antibiotics was 8.0 days. Second-generation

cephalosporins were administered to 199 patients (88.1 %).

The Kaplan–Meier plot indicated that recurrences were

more frequent within 100 days of AC; these were defined

as early recurrences. The recurrence rate was 13.7 % (31/

226) at a median follow-up of 308.5 days (early recur-

rences: 19/226 [8.4 %]). The duration of parenteral anti-

biotic use significantly correlated with early recurrence

(hazard ratio: 0.83; 95 % confidence interval, 0.73–0.95;

p = 0.005). Generalized additive models revealed that

patients using parenteral antibiotics longer than 8 days

were less likely to suffer from early recurrence.

Conclusions The rate of recurrence of AC in patients who

received antibiotics alone was low. The recurrence rate was

higher within 100 days of AC. Because of the inherent

limitations of a retrospective study, further research is

needed to identify factors associated with early recurrence.

Introduction

Acute cholecystitis (AC) is an inflammatory disease of the

gallbladder, and [90 % of AC cases are associated with

gallstones [1]. Cholecystitis represents one of the most

common emergency admissions in surgical practice [2].

Cholecystectomy has been the gold standard treatment

for AC. However, the optimal timing for cholecystectomy

in patients with AC is a point of controversy. With the

advent of laparoscopic cholecystectomy, early surgery was

considered safe and cost effective for the management of

AC [2]. However, initial nonoperative treatment, including

antibiotic treatment with or without percutaneous transhe-

patic cholecystostomy (PTC), has been proposed for high-

risk patients to prevent postoperative morbidity, and

interval cholecystectomy (IC) has been reserved for

patients with recurrent AC [3]. Some researchers have

suggested that PTC, instead of IC, may serve as a definitive

treatment for AC [4].

C.-H. Wang � H.-C. Chou � W.-C. Lien (&)

Department of Emergency Medicine, National Taiwan

University and National Taiwan University Hospital, No. 7,

Chung-Shan S. Road, Taipei 100, Taiwan

e-mail: wanchinglien@ntu.edu.tw

K.-L. Liu

Department of Medical Imaging, National Taiwan University

and National Taiwan University Hospital, No. 7, Chung-Shan S.

Road, Taipei 100, Taiwan

H.-P. Wang

Department of Internal Medicine, National Taiwan University

and National Taiwan University Hospital, No. 7, Chung-Shan S.

Road, Taipei 100, Taiwan

Y.-M. Wu

Department of Surgery, National Taiwan University and

National Taiwan University Hospital, No. 7, Chung-Shan S.

Road, Taipei 100, Taiwan

123

World J Surg (2014) 38:347–354

DOI 10.1007/s00268-013-2311-3

An increasing number of studies have investigated PTC

for AC, with a particular focus on elderly and other high-

risk patients with serious comorbidities [3, 4]. However,

many non-high-risk patients have completed antibiotic

treatment without IC in clinical practice [5], and the

management of these patients has not been well investi-

gated. In a population-based study, AC patients who did

not undergo IC comprised 43.2 % (11,118 of 25,743) of the

cohort, and the mean patient age was 64.3 years [5].

Although guidelines recommended IC for patients who

did not initially undergo early cholecystectomy, there were

many patients in clinical practice who did not return for IC

[5]. Knowledge of the prognosis for patients managed with

antibiotics alone for AC may aid clinicians in deciding for

or against surgical intervention. The present study was

carried out retrospectively with the aim of estimating the

recurrence rate in all adult AC patients receiving antibiotic

treatment. The factors associated with recurrence were also

investigated.

Materials and methods

This retrospective cohort study was performed by review-

ing the medical records of patients with AC who were

admitted through the emergency department of National

Taiwan University Hospital (NTUH) between October 1,

2004, and November 30, 2010. National Taiwan University

Hospital is a 2,600-bed urban medical center providing all

levels of care. Patients were identified using the interna-

tional classification of diseases, 9th Revision, clinical

modification codes 574.0, 574.3, 574.6, 574.8, 575.0,

575.12, and 575.4. Acute cholecystitis was diagnosed

through a combination of patient history, physical exami-

nation, and laboratory analysis. The diagnosis had to have

been confirmed by characteristic imaging findings on

ultrasonography (US) or computed tomography (CT)

according to the Tokyo guidelines [6]. Patients were

excluded if they had co-existing gallstone pancreatitis,

choledocholithiasis, or hepatobiliary malignancy. Patients

who solely received antibiotic treatment during their

admission were included for analysis. Patients with PTC

insertion were excluded. This study was approved by the

Institutional Review Board of NTUH prior to data

collection.

The basic demographics, presenting vital signs, chief

symptoms (fever or abdominal pain), physical findings

(including right upper quadrant tenderness and Murphy’s

sign), laboratory data (including white blood cell counts,

and C-reactive protein and bilirubin levels), imaging find-

ings (including gallbladder wall thickening, the presence of

gallstone, distention of the gallbladder, and surrounding

fluid accumulation) on US/CT, and the timing of antibiotic

use were recorded. Patients were graded according to the

Tokyo guidelines (Table 5 in appendix) [6]. Comorbidities

were recorded according to the Charlson comorbidity index

[7]. Gangrenous cholecystitis, emphysematous cholecysti-

tis, gallbladder perforation, empyema, and pericholecystic

abscess were categorized as complicated cholecystitis.

The primary outcome was the recurrence of AC after

antibiotic treatment. Secondary outcomes included IC and

death. The definition of early and IC varied across different

studies [2]. In this study, early cholecystectomy was

defined as cholecystectomy within the first 7 days after

symptom onset [2], whereas IC was defined as cholecys-

tectomy performed [7 days after symptom onset. Medical

records were reviewed regularly to determine whether

patients eventually returned for cholecystectomy after ini-

tial discharge.

Statistical analysis

Data analysis was performed with the R 2.12.1 software (R

Foundation for Statistical Computing, Vienna, Austria).

Categorical data were compared with Fisher’s exact test,

and continuous data were examined with the Wilcoxon

rank-sum test. A two-tailed p value of B0.05 was consid-

ered statistically significant.

For calculating recurrence-free survival curve in a

Kaplan–Meier plot, the starting time was defined as the

date of symptom onset and the event time as the date of AC

recurrence. Interval cholecystectomy, death, and the end of

data collection (May 31, 2011) were the censoring events.

The depicted Kaplan–Meier plot indicated that AC recur-

red more frequently within 100 days of symptom onset.

Therefore, recurrence and IC within 100 days of AC were

designated as early recurrence and IC, respectively.

Multivariate survival analysis was conducted to identify

factors associated with early recurrence or IC using the

Cox proportional hazards model. All potential covariates

for variable selection are listed in Table 1. The stepwise

variable selection procedure (with iterations between the

forward and backward steps) was applied to remove vari-

ables that were not significant and to determine the most

parsimonious model by minimizing the value of Akaike’s

information criterion. Generalized additive models were

applied to detect the nonlinear effects of continuous

covariates. Recurrence-free survival curves were compared

with a two-sided log rank test.

Results

A total of 947 patients with AC were admitted through the

emergency department between October 2004, and

November 2010. Of these, 168 patients with co-existing

348 World J Surg (2014) 38:347–354

123

Table 1 Demographic and clinical characteristics of enrolled patients

Characteristics All patientsa Patients with early

recurrenceaPatients without

early recurrenceap valueb

Number 226 19 207

Age (years) 62.2 (15.8) 57.0 (15.7) 62.7 (15.7) 0.115

Male 144 (63.7 %) 8 (42.1 %) 136 (65.7 %) 0.048*

Comorbidity

Diabetes mellitus 60 (26.5 %) 3 (15.8 %) 57 (27.5 %) 0.415

Cerebral vascular disease 20 (8.8 %) 3 (15.8 %) 17 (8.2 %) 0.229

Coronary artery disease 34 (15 %) 4 (21.1 %) 30 (14.5 %) 0.499

Malignancy 20 (8.8 %) 2 (10.5 %) 18 (8.7 %) 0.678

Charlson comorbidity index 1.1 (1.5) 1.1 (1.2) 1.1 (1.5) 0.704

Previous abdominal surgery 43 (19 %) 3 (15.8 %) 40 (19.3 %) [0.999

Clinical symptoms and signs on presentation

Body temperature 37.2 (1.2) 37.1 (1.3) 37.2 (1.1) 0.920

Body temperature [38 �C 56 (24.8 %) 5 (26.3 %) 51 (24.6 %) [0.999

Abdominal pain 183 (81.0 %) 17 (89.5 %) 166 (80.2 %) 0.540

Onset of symptoms before presentation

at emergency department (days)

2.1 (2.4) 2.5 (3.6) 2.1 (2.2) 0.642

Laboratory studies

White blood cell count, 103 lL 12.6 (5.6) 10.6 (3.6) 12.8 (5.7) 0.049*

Positive blood culture 41 (18.1 %) 2 (10.5 %) 39 (18.8 %) [0.999

Diagnostic tools

Ultrasonography (US) 186 (82.3 %) 13 (68.4 %) 173 (83.6 %) 0.115

Computed tomography (CT) 154 (68.1 %) 15 (78.9 %) 139 (67.1 %) 0.440

Findings on US or CT

Gallstones or sludge 193 (85.4 %) 16 (84.2 %) 177 (85.5 %) 0.745

Pericholecystic fluid 63 (27.9 %) 5 (26.3 %) 58 (28.0 %) [0.999

Fatty liver 109 (48.2 %) 9 (47.4 %) 100 (48.3 %) [0.999

Complicated cholecystitis 15 (6.6 %) 1 (5.3 %) 14 (6.8 %) [0.999

Severity grade per Tokyo guidelines 0.623

Grade I 145 (64.2 %) 11 (57.9 %) 134 (64.7 %)

Grade II 77 (34.1 %) 8 (42.1 %) 69 (33.3 %)

Grade III 4 (1.8 %) 0 (0.0 %) 4 (1.9 %)

Early operation indicated by surgeons 124 (54.9 %) 11 (57.9 %) 113 (54.6 %) 0.815

Early operation rejected by patients 96 (42.5 %) 9 (47.4 %) 87 (42.0 %) 0.809

Medical ward admission 201 (88.9 %) 16 (84.2 %) 185 (89.3) 0.450

Duration, days

Total antibiotics 14.4 (8.2) 10.4 (6.3) 14.8 (8.3) 0.010*

Parenteral 8.0 (4.8) 5.4 (4.0) 8.3 (4.8) 0.012*

2nd generation cephalosporins 199 (88.1 %) 16 (84.2 %) 183 (88.4 %) 0.482

Oral 6.4 (6.9) 5.1 (4.6) 6.5 (7.0) 0.250

Fever 1.8 (2.0) 1.5 (2.1) 1.9 (2.0) 0.255

Parenteral analgesic use 0.9 (1.3) 1.0 (1.0) 0.9 (1.3) 0.458

Nil per os 2.6 (2.1) 2.5 (2.3) 2.6 (2.1) 0.551

Hospital stay 8.7 (6.9) 7.4 (5.3) 10.7 (7.3) 0.029*

a Data are represented as mean (SD) or counts (%)b Comparison was made between patients with and without early recurrences

* p value \0.05

World J Surg (2014) 38:347–354 349

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gallstone pancreatitis, choledocholithiasis, or hepatobiliary

malignancy were excluded. Of the remaining 779 patients,

395 patients underwent early cholecystectomy, 158

underwent PTC, and 226 completed antibiotic treatment.

The 226 patients who received antibiotic treatment alone

were further analyzed in the present study.

Table 1 summarizes the demographic and clinical

characteristics of the patients included in the study. There

were 144 male patients and 82 female patients with a mean

age of 62.2 years. 193 (85.4 %) patients had gallstones or

sludge detected on US or CT. The mean time from

symptom onset to presentation at the emergency depart-

ment was 2.1 days. Of the 226 patients studied, 124

(54.9 %) were considered suitable for early cholecystec-

tomy after surgeon consultation, whereas 96 patients

(41.2 %) rejected early cholecystectomy after discussion

with surgeons. The average duration of antibiotic use was

8.0 days for parenteral antibiotics and 6.4 days for oral

antibiotics. Second-generation cephalosporins were

administered to 199 patients (88.1 %).

The Kaplan–Meier plot demonstrated that there were

more frequent recurrences within 100 days of AC than

during the subsequent period (Fig. 1). Accordingly, this time

point was used to differentiate between early and late events,

including recurrence and IC. As shown in Table 1, patients

with and without early recurrence did not differ significantly

in demographic or clinical characteristics, except in gender,

white blood cell count, the duration of total and parenteral

antibiotic use, and length of hospital stay.

Table 2 summarizes the primary and secondary out-

comes of the study patients. The median follow-up period

was 308.5 days. The mean time of IC and recurrence were

103.0 and 214.5 days, respectively. 62 patients (27.4 %)

underwent early IC, whereas 19 patients (8.4 %) experi-

enced early recurrence.

Multivariate survival analysis using a Cox proportional

hazards model revealed that the duration of parenteral

antibiotic use was significantly associated with early

recurrence (hazard ratio [HR], 0.81; 95 % confidence

interval [CI], 0.71–0.93; p = 0.002). In Fig. 2, under the

generalized additive model, the nonparametric smoothing

plot shows that the probability of early recurrence was

lower in patients with parenteral antibiotic use for[8 days

than in patients with a shorter duration (B8 days) of anti-

biotic use.

As shown in Fig. 3, Kaplan–Meier plots stratified by the

duration of parenteral antibiotic use demonstrated that the

rate of early recurrence was significantly higher for patients

who received parenteral antibiotics for B8 days than for

those who received it for [8 days (p = 0.028 by the log

rank test).

Baseline characteristics were compared between

patients with and without early IC. As shown in Table 3,

univariate analysis revealed significant differences between

groups in cerebrovascular disease and the Charlson

comorbidity index. Multivariate survival analysis using a

Cox proportional hazards model indicated that several

variables were significantly associated with early IC,

including age (60–85 years; HR, 2.09; 95 % CI, 1.23–3.55;

p = 0.007), male gender (HR, 0.60; 95 % CI, 0.36–0.99;

p = 0.045), Charlson comorbidity index (HR, 0.62; 95 %

CI, 0.48–0.81; p \ 0.001), surgeon recommendation for

early surgery (HR, 2.08; 95 % CI, 1.04–4.13; p = 0.037),

and early surgery option rejected by patients (HR, 0.37;

95 % CI, 0.18–0.76; p = 0.007) (Table 4).

Discussion

Population-based studies have reported that early chole-

cystectomy rates were *50 % in the United States from

2000 to 2005 [8] and only 14.7 % in England from 2003 to

2005 [5]. In England, of the 20,924 patients who did not

undergo an emergency cholecystectomy, 9,806 patients

(46.9 %) subsequently underwent IC, whereas the

remaining 11,118 patients (53.2 %) did not [5]. In our

Fig. 1 Kaplan–Meier plots of

the recurrence-free survival

curve in patients treated with

antibiotic treatment for acute

cholecystitis. Dotted lines

represent the 95 % confidence

interval

350 World J Surg (2014) 38:347–354

123

study, *35.4 % of patients (80/226) with initial antibiotic

treatment underwent IC, whereas 64.6 % of patients (146/

226) did not.

Few, if any, studies have reported the follow-up and

prognosis of AC patients who did not undergo IC. For

patients with gallstone disease,[50 % remained or became

asymptomatic during the long-term follow-up in a 10-year

prospective population-based cohort study [9]. Among

patients with severe symptoms, only 8.4 % developed

complications [9]. In a retrospective hospital-based study

by McGillicuddy et al. [3] the recurrence rate was *4 %

with a mean follow-up duration of 30 months in elderly

AC patients receiving antibiotic treatment alone. The

principal findings of our study showed a recurrence rate of

*13.7 % (31/226) with a median follow-up of 308.5 days.

Most patients who did not undergo cholecystectomy did

not experience recurrent AC.

McGillicuddy et al. [3] reported a much lower recur-

rence rate than our study (4 vs. 13.7 %). However, in the

study by McGillicuddy et al. a high proportion of patients

(78/126, 61.9 %) ended follow-up with death, which might

Table 2 Outcomes of enrolled patients

Outcome Enrolled patients

(n = 226)

Follow-up period (days) 308.5 (1,139.8)a

Total recurrence 31 (13.7 %)b

Total interval cholecystectomy 80 (35.4 %)b

Time to recurrence (days) 214.5 (343.3)c

Time to interval cholecystectomy (days) 103.0 (179.0)c

Patients with

Early recurrenced 19 (8.4 %)b

Late recurrenced 12 (5.3 %)b

Early interval cholecystectomyd 62 (27.4 %)b

Late interval cholecystectomyd 18 (8.0 %)b

Death from other causes 3 (1.3 %)b

a Data are expressed as the median (IQR)b Data are expressed as counts (%)c Data are expressed as the mean (standard deviation)d ‘‘Early’’ and ‘‘late’’ indicate the event occurred at B100 or

[100 days after initial onset of acute cholecystitis, respectively

Fig. 2 Generalized additive

models for the duration of

parenteral antibiotic use

adjusted by age and gender

Fig. 3 Kaplan–Meier plots

stratified by the duration of

parenteral antibiotic use

World J Surg (2014) 38:347–354 351

123

influence the observation of recurrence and underestimate

its real incidence. Nonetheless, their data were still valu-

able in the assessment of surgical risk–benefit profile in the

elderly group. Unlike the study by McGillicuddy et al.,

ours did not focus on the elderly group only. Our patients

were generally younger (mean age: 78.1 vs. 62.2 years)

and healthier (coronary artery disease proportion: 72.2 vs.

15 %) with comparatively lower anesthesia risk for emer-

gent operation than patients in the study by McGillicuddy

et al. By current accepted management standards of AC,

patients should receive emergent or IC if no contraindica-

tions exist, such as cardiopulmonary compromise. How-

ever, even though most of our patients were considered

suitable for early cholecystectomy (124/226, 54.9 %), only

35.4 % of them (80/226) received IC.

Riall et al. [10] reported significant mortality and mor-

bidity in patients with nonoperative treatment. However, the

diagnosis of AC in their study depended on the database

codes rather than review of medical records by clinicians.

The accuracy of database codes for AC had been questioned

[5]. We sometimes found that making the clinical distinction

between biliary colic and acute cholecystitis was difficult.

Because surgical or pathological proof of AC was not

available in the present study, the clinical findings of AC had

to be verified by imaging studies, such as US or CT, to ensure

correctness and validity of the diagnosis.

The Kaplan–Meier plot demonstrated that the recurrence

rate of AC was higher within 100 days of the initial onset of

symptoms than in the subsequent period (8.4 vs 5.3 %).

Conventionally, IC was performed 6–12 weeks after AC [2].

Therefore, we decided to focus our investigation on a com-

parison of patients who did and did not experience recur-

rence within 100 days of AC. Multivariate survival analysis

indicated that the duration of parenteral antibiotic use sig-

nificantly correlated with early recurrence: patients receiv-

ing parenteral antibiotics for [8 days suffered less from

early recurrence than those receiving antibiotics for

B8 days. Although this statistical association existed, the

effect of parenteral antibiotics was less likely to persist after

hospital discharge to prevent the early recurrence. Clinically,

it is possible that the reason patients received antibiotics for a

longer duration might be that they suffered from more severe

inflammation than those with shorter duration antibiotic

treatment. Also, fibrosis of the gallbladder after a period of

severe inflammation might have led to a lower recurrence

rate in the later period. Although we had controlled most

important clinical and laboratory variables in our model, we

may still have missed some important ones that would clarify

the problem of confounding by indication, which should be

further investigated in prospective researches. In contrast,

when compared with the early IC rate, the early recurrence

rate was relatively low (27.4 vs. 8.4 %). The number of

censoring events was almost three times the number of pri-

mary outcomes, which might further weaken the power of

statistical analysis.

In the present study, early cholecystectomy was defined

as cholecystectomy within 7 days of symptom onset. This

Table 3 Demographic characteristics of patients with and without

early IC

Characteristics Patients with

early ICaPatients

without

early ICa

p valueb

Number 62 164

Age (years) 62.7 (14.2) 62.0 (16.3) 0.845

Male 35 (56.5 %) 109 (66.5 %) 0.167

Comorbidity

Diabetes mellitus 14 (22.6 %) 46 (28.0 %) 0.500

Cerebral vascular

disease

1 (1.6 %) 19 (11.6 %) 0.017*

Coronary artery disease 6 (9.7 %) 28 (17.1 %) 0.212

Malignancy 5 (8.1 %) (9.1 %) [0.999

Charlson comorbidity

index

0.7 (1.1) 1.3 (1.6) 0.002*

Previous abdominal

surgery

10 (16.1 %) 33 (20.1 %) 0.572

Imaging findings in US or CT

Gall bladder stones or

sludge

57 (91.9 %) 136 (82.9 %) 0.095

Complicated

cholecystitis

6 (9.7 %) 9 (5.5 %) 0.367

Severity grade per Tokyo guidelines 0.759

Grade I 37 (60.3 %) 108(65.6 %)

Grade II 24 (38.1 %) 53 (32.5 %)

Grade III 1 (1.6 %) 3 (1.8 %)

Early operation indicated

by surgeons

33 (53.2 %) 91 (55.5 %) 0.767

Early operation rejected

by patients

22 (35.5 %) 74 (45.1 %) 0.228

Medical ward admission 53 (85.5 %) 148 (90.2 %) 0.344

a Data are expressed as mean (SD) or counts

* p value of \0.05

Table 4 Multivariate survival analysis for early IC using a Cox

proportional hazard model

Covariates Hazard

ratio

95 % confidence

interval

p value

Age 60–85 years 2.09 1.23–3.55 0.007*

Male gender 0.60 0.36–0.99 0.045*

Charlson comorbidity index 0.62 0.48–0.81 \0.001*

Early surgery recommended

by surgeons

2.08 1.04–4.13 0.037*

Early surgery rejected

by patients

0.37 0.18–0.76 0.007*

* p \ 0.05

352 World J Surg (2014) 38:347–354

123

time frame was chosen because some trials have suggested

that early operation performed during this period was as

safe as surgery performed within 3 days of symptom onset

[11]. In contrast, the timing of IC was more controversial.

The term interval has been interpreted liberally, as some-

where between a few weeks and a few months after AC,

time periods that were assumed to be sufficient for the

acute inflammation to subside completely [1]. In the past

40 years, including the eras of open and laparoscopic

cholecystectomy, most ICs reported in clinical trials were

performed between 6 and 12 weeks after AC [2]. However,

in some trials, IC was conducted earlier than 6 weeks after

AC; for example, Norrby et al. [12] defined IC as chole-

cystectomy after initial conservative treatment, and Chan-

dler et al. [13] defined it as cholecystectomy after the

resolution of symptoms or after 5 days of treatment. To

maximize the available information, we defined IC as

operations performed at least 1 week after symptom onset.

The total rate of IC in our study, including both early and

late operations, was 35.4 % (80/226). The rate of IC varied

significantly across studies from 23.8 % (44/185) to 80.7 %

(46/57) [3, 5, 14]. This wide variation may be explained by

differences in patient cohorts, selection by surgeons, and

most important, patient decisions. As noted in our analysis,

the attitude of patients toward early cholecystectomy sig-

nificantly correlated with early IC (HR, 0.37; 95 % CI,

0.18–0.76; p = 0.007). Patients who initially refused early

cholecystectomy were less likely to undergo IC in the future.

Other factors associated with early IC, including age, gender,

and the Charlson comorbidity index, may reflect the choices

made by surgeons and patients.

The results of population-based studies have shown that

[50 % of AC patients did not undergo early cholecystec-

tomy and[50 % of these patients did not undergo IC [5, 8].

The prognosis for these AC patients without surgery was

seldom reported. With advances in medical treatment, the

necessity of cholecystectomy may be further examined.

Percutaneous transhepatic cholecystostomy, a nonoperative

intervention, was studied as a bridge to surgery or as defin-

itive management in AC patients with high surgical risk [4].

However, few, if any, studies have investigated antibiotic

treatment in AC patients. Our results might provide some

important surgical risk–benefit information for patients or

clinicians and support a randomized, controlled trial to

compare AC patients who undergo early cholecystectomy

with those who receive antibiotic treatment.

The findings from our study do not indicate that anti-

biotic treatment was sufficient for patients with AC, but

tried to provide some benefit–risk profiles in this group.

Combined with the development of PTC in recent years,

the treatment algorithm for AC may be updated to focus on

nonoperative management, as many patients were inter-

ested in this method.

Limitations

The first limitation of the present study is that the number of

patients with recurrence was relatively small, which might

introduce a type II error. Second, although our hospital

provides all levels of care, the cohort from a single medical

center may introduce some selection bias. Third, the recur-

rence rate may have been underestimated because we could

not verify whether patients experienced recurrence or

underwent IC at other hospitals. However, all patients were

sent by emergency medical services to our emergency

department at the initial onset, suggesting that many would

be sent to our hospital by the service in the case of recurrence.

This may compensate to some extent for any underestima-

tion. Finally, because of the retrospective nature of this

study, there were no a priori criteria for surgical or antibiotic

treatment. This decision was negotiated between patients

and clinicians. Although this may introduce selection bias,

the result may be more applicable to daily practice.

Conclusions

The recurrence of AC in patients who received antibiotics

alone was low. The recurrence rate was higher within

100 days of AC. Because of the inherent limitations of a

retrospective study, further studies are needed to identify

factors associated with early recurrence.

Conflict of interest We declare that we have no conflicts of interest.

Funding None.

Appendix

See Table 5

Table 5 Severity according to the Tokyo guidelines for acute

cholecystitis

Grade Criteria

1 Mild Acute cholecystitis that does not meet the criteria

for a more severe grade

Mild gallbladder inflammation, no organ

dysfunction

2 Moderate 1. Elevated WBC count ([18,000/mm3)

2. Palpable tender mass in the right upper

abdominal quadrant

3. Duration of complaints [72 h

4. Marked local inflammation (biliary peritonitis,

pericholecystic abscess, hepatic abscess,

gangrenous cholecystitis, emphysematous

cholecystitis)

World J Surg (2014) 38:347–354 353

123

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Table 5 continued

Grade Criteria

3 Severe Acute cholecystitis accompanied by dysfunction

in any one of the following organs or systems

1. Cardiovascular dysfunction (hypotension

requiring treatment with dopamine [[5 lg/kg

per min] or any dose of dobutamine)

2. Neurologic dysfunction (i.e., decreased level

of consciousness)

3. Respiratory dysfunction (PaO2/FiO2 ratio,

\300)

4. Renal dysfunction (oliguria or creatinine

[2.0 mg/dL)

5. Hepatic dysfunction (PT-INR [1.5)

6. Hematologic dysfunction (platelet count,

\100,000/mm3)

WBC white blood cell, PaO2 partial pressure of oxygen in arterial

blood, FiO2 fraction of inspired oxygen, PT-INR prothrombin time-

international normalized ratio

354 World J Surg (2014) 38:347–354

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