- Email: [email protected]
Should acute cholecystitis be operated in the 24 h following symptom onset? A retrospective cohort study
Accepted Manuscript Should acute cholecystitis be operated in the 24 hours following symptom onset? A retrospective cohort study Dr. Mahdi Bouassida, Lamine Hamzaoui, Bassem Mroua, Mohamed Fadhel Chtourou, Slim Zribi, Mohamed Mongi Mighri, Hassen Touinsi PII:
S1743-9191(15)01367-9
DOI:
10.1016/j.ijsu.2015.11.049
Reference:
IJSU 2356
To appear in:
International Journal of Surgery
Received Date: 1 November 2015 Revised Date:
16 November 2015
Accepted Date: 24 November 2015
Please cite this article as: Bouassida M, Hamzaoui L, Mroua B, Chtourou MF, Zribi S, Mighri MM, Touinsi H, Should acute cholecystitis be operated in the 24 hours following symptom onset? A retrospective cohort study, International Journal of Surgery (2015), doi: 10.1016/j.ijsu.2015.11.049. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset ? A retrospective cohort study. Mahdi Bouassida (1), Lamine Hamzaoui (2), Bassem Mroua (1), Mohamed Fadhel
RI PT
Chtourou (1), Slim Zribi (1), Mohamed Mongi Mighri (1), Hassen Touinsi (1) 1- Department of surgery ; Mohamed Tahar Maamouri Hospital ; Nabeul ; Tunisia. 2 : Department of gastroenterology ; Mohamed Tahar Maamouri Hospital ; Nabeul ;
SC
Tunisia.
M AN U
Corresponding author :
Dr Bouassida Mahdi: postal address: 8000 Mrazga, Nabeul, Tunisia. Email: [email protected]
AC C
EP
TE D
Telephone: 001626680963. Fax: 001672285683.
1
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset? A retrospective cohort study. Abstract
RI PT
Background: Early laparoscopic cholecystectomy is the gold standard for management of acute cholecystitis (AC). Nevertheless, the definition used for early phase remained unclear. We aimed to compare the clinical outcome and cost of
SC
immedite (patients undergoing laparoscopic cholecystectomy within 24 h following symptom onset) versus early laparoscopic cholecystectomy (patients managed 25-72
M AN U
h following symptom onset) for acute cholecystitis.
Methods : A retrospective analysis was performed. The outcomes of 143 patients undergoing laparoscopic cholecystectomy within 24 h (ICG) were compared to 350 patients managed 25-72 h following symptom onset (ECG) for acute cholecystitis.
TE D
Results : There were significantly more diabetic patients in the early laparoscopic group (ECG). All other characteristics were comparable (demographic, clinical,
EP
biologic and ultrasonographic characteristics) between the two groups. The rate of conversion to open surgery was significantly higher in the ECG. Overall post
AC C
operative morbidity and specific morbidity did not differ significantly between the groups. Total hospital stay was longer in the ECG. Direct medical costs were higher in the ECG.
Conclusions : Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset of symptoms, significantly reduced conversion to open surgery and total hospital stay without increasing postoperative complications.
2
ACCEPTED MANUSCRIPT Key words: acute cholecystitis ; laparoscopy ; immediate cholecystectomy ; early
AC C
EP
TE D
M AN U
SC
RI PT
cholecystectomy ; conversion ; morbidity.
3
ACCEPTED MANUSCRIPT Introduction Laparoscopic cholecystectomy is the gold standard for the management of acute cholecystitis (AC) [1]. Randomized controlled trials and meta-analyses had shown the
RI PT
benefits of early surgery compared with delayed cholecystectomy with respect to hospital stay and costs, with no significant difference in morbidity and mortality [2,3,4,5]. Nevertheless, the definition used for early phase was unclear because timing of surgery was expressed relative to differing events, such as symptom onset
SC
[6] and time of admission [7]. The aim of this study was to compare the outcomes of
M AN U
patients undergoing laparoscopic cholecystectomy (LC) within 24 h of symptom onset
AC C
EP
TE D
with patients managed 25 to 72 h after symptom onset for AC.
4
ACCEPTED MANUSCRIPT Materials and methods: A retrospective analysis was performed. The outcomes of patients undergoing laparoscopic cholecystectomy within 24 h (ICG) were compared with patients
RI PT
operated 25-72 h following symptom onset (ECG) for acute cholecystitis. The diagnosis and assessment of acute cholecystitis were performed in accordance with the diagnostic criteria of the Revised Tokyo Guidelines published in 2013 [8].
SC
Pathologic diagnoses were made using current standard definitions and criteria used in surgical pathology literature, with similar definitions described by Fitzgibbons et al.
M AN U
in their review [9]. All patients were placed on intravenous antibiotics upon admission which was not continued after surgery. All surgeries in this study were performed by experienced attending surgeons. Laparoscopic cholecystectomy was carried out using three incisions (3 port laparoscopic cholecystectomy technique) with
TE D
pneumoperitoneum installed via a sub-umbilical mini-laparotomy with a maximum intraabdominal pressure at 12 mmHg.
The patients were divided into two groups: the immediate cholecystectomy group
EP
(ICG) and the early cholecystectomy group (ECG). We analyzed and compared the
AC C
clinical features and surgical outcomes of the two groups, including gender, age, comorbidities, severity of acute cholecystitis, WBC count, ultrasonographic findings, conversion to open surgery, presence of postoperative complications, and postoperative hospital stay length. Primary endpoints included the rates of conversion to open surgery and postoperative
complications.
Secondary
endpoints
postoperative hospital stay and direct medical costs.
included
the
length
of
5
ACCEPTED MANUSCRIPT This work was fully compliant with the STROBE criteria. Statistical analysis was conducted using the Fisher’s exact test and the X2 test for categorical data, and the independent t test was used for continuous data. Results
RI PT
are expressed as mean ± standard deviation (SD). Statistical significance was defined as a p value of 0.05. All statistical analyses were performed using SPSS for
AC C
EP
TE D
M AN U
SC
Windows, version 19.0 (SPSS, Chicago, IL, USA).
Results
6
ACCEPTED MANUSCRIPT Between
January
2005
and
January
2013,
646
patients
underwent
cholecystectomies for AC at the Department of Surgery, Mohamed Tahar Maamouri Hospital of Nabeul; 493 of these patients in whom laparoscopic cholecystectomy was performed were considered to be enrolled in the study. Patients treated more than 3
RI PT
days after symptom onset (120 patients) and patients with alternate diagnoses of choledocholithiasis or gallstone pancreatitis (33 patients), were excluded. All patients were operated in the admission day.
SC
There were 137 men and 356 women aged 19– 93 years (mean, 53 years).
M AN U
According to the 2013 Revised Tokyo Guidelines, acute cholecystitis severity was classified as mild (n=258), moderate (n=231), and severe (n=4). One hundred forty three patients were managed within 24 h of symptom onset (the immediate cholecystectomy group ICG), while, 350 patients were managed 25-72 h following symptom onset (the early cholecystectomy group ECG). The demographic
TE D
characteristics of the groups are summarized in Table 1. There were significantly more diabetic patients in the ECG. In the ICG and the ECG, the mean days from symptom onset to surgery were 0.7±0.38 days and 2.8±1.4 days, respectively
EP
(p<103). All other characteristics were comparable (demographic, clinical, biologic
AC C
and ultrasonographic characteristics). The rate of gangrenous cholecystitis was significantly higher in the ECG (25.43% vs. 14% in the ICG; p=0.005). The rate of conversion to open surgery was also significantly higher in the ECG (13.43% vs. 6.29% in ICG, p=0.023). The reasons for conversion consisted of inability to define anatomy in the Calot’s triangle (45 cases), necessity to explore the common bile duct (5 cases), or bleeding (6 cases). Prophylactic drainage was required in 59.44% of cases in the ICG and in 74.85% of cases in the ECG (p=0.001).
7
ACCEPTED MANUSCRIPT Overall postoperative morbidity (3.5% in the ICG vs.3.48 in the ECG; p=0.97) and specific morbidity (1.4% in the ICG vs.1.7 in the ECG; p=0.7) did not differ significantly between the groups. The specific complications in the ICG were bile leak in 2 patients. Six specific complications, including two patients with bile leak, one
RI PT
patient with bile duct injury, two patients with intraabdominal infection and one patient with wound infection were recorded in the ECG. The rate of reoperations did not differ significantly between the groups (0.7% in the ICG vs. 1.4% in the ECG; p=0.9).
SC
No mortality occurred in either group. The total hospital stay was significantly longer in the ECG (4.76±1.87 days vs. 2.61±1.19 days in the ICG; p<10-3). The direct
AC C
EP
TE D
TND in the ICG; p<10-3) (table 2).
M AN U
medical costs were significantly higher in the ECG (234±63.23 TND vs. 125.85±53.44
Discussion
8
ACCEPTED MANUSCRIPT Nowadays, laparoscopic cholecystectomy is the gold standard for the management of acute cholecystitis (AC) [1]. Current data suggest that early LC for acute cholecystitis is superior to late or delayed LC [10], but the definition for early phase was unclear because the timing of surgery was expressed relative to different events,
RI PT
such as symptom onset and time of admission. In 2013, the Tokyo Guidelines were revised, stating that it was better to perform cholecystectomy within 72 h of symptom onset. In this study, “early” was defined with respect to symptom onset; early
SC
cholecystectomy was performed within a time interval of 72 h, the so called golden 72 h [8]. The aim of this study was to compare the outcomes of patients with AC
M AN U
operated within 24 h of symptom onset (immediate laparoscopic cholecystectomy ICG) to those operated 25-72 h following symptom onset (early laparoscopic cholecystectomy ECG). The ICG and ECG were comparable with regard to age, gender, clinical, biological and ultrasonographic characteristics, but there were
TE D
significantly more diabetic patients in the ECG: a possible explanation would be the altered response to inflammation in diabetic patients resulting in a delay in medical
EP
consultation in these patients [11].
In our experience, the time from symptom onset correlates well with the grade of
AC C
severity: gangrenous cholecystitis were significantly more frequent in the ECG. The progression of local inflammation that occurs in the gallbladder over several days leads to hardening of gallbladder wall, loss of normal layered architecture and oedema in the surrounding structures, resulting in an increased rate of conversion to open surgery. In fact, the conversion rate was significantly higher in the ECG. Surgical dissection within this critical period, therefore, appears easier due to lack of surrounding inflammatory resections [12]. This is also reflected in the lower rates of complication and converse to open surgery in the ICG. To the best of our knowledge,
9
ACCEPTED MANUSCRIPT only one previous study compared outcomes of patients undergoing laparoscopic cholecystectomy within 24 h to those of patients managed 25-72 h following symptom onset for acute cholecystitis [6]. Unlike the present study, the previous study did not find any significant difference between the groups in conversion rates. This might be
patients in each group) [6].
RI PT
due to a type II statistical error in that study with a relatively small size of cohorts (35
In agreement with previous studies, there were no significant differences in the rates
between
the
two
groups
[6,10].
Immediate
SC
morbidity
laparoscopic
M AN U
cholecystectomy significantly reduced total hospital stay without increasing intra- and postoperative complications [13]. As the ICG reduced medical costs, this is crucial especially for a country with limited resources such as Tunisia. These results are consistent with those reported in a recent multicenter randomized trial which revealed that the costs associated with delayed laparoscopic treatment were approximately
TE D
50 % higher than those associated with early surgery because of longer total hospital stay [12].
EP
Limitations : This study is limited by the retrospective study design but it was impossible to randomize patients because we defined the two groups from symptom
AC C
onset to surgery and laparoscopic cholecystectomy was carried out on the date of hospital admission.
In conclusion, laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset of symptoms, significantly reduced the rate of conversion to open surgery and the total hospital stay without increasing intra- and postoperative complications. The Author Disclosure Statement: nothing.
10
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
References 1- Bouassida M, Charrada H, Feidi B, Chtourou MF, Sassi S, Mighri MM et al. Could the Tokyo guidelines on the management of acute cholecystitis be adopted in
11
ACCEPTED MANUSCRIPT developing countries? Experience of one center. Surg Today 2015 (Article in press). DOI 10.1007/s00595-015-1207-2. 2- Lo CM, Liu CL, Fan ST, Lai EC,Wong J. Prospective randomized study of early
RI PT
versus delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 1998;227:461-7.
3- Lau H, Lo CY, Patil NG, Yuen WK. Early versus delayed-interval laparoscopic
SC
cholecystectomy for acute cholecystitis: A metaanalysis. Surg Endosc 2006;20:82-7. 4- Shikata S, Noguchi Y, Fukui T. Early versus delayed cholecystectomy for acute
M AN U
cholecystitis: A meta-analysis of randomized controlled trials. Surg Today 2005;35:553-60.
5- Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR.
Metaanalysis of
randomized controlled trials on the safety and effectiveness of early versus delayed
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laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 2010;97:141-50. 6- Ambe P, Weber SA, Christ H, Wassenberg. Cholecystectomy for acute How time-critical are
the
so called "golden 72 hours"?
EP
cholecystitis.
Or better "golden 24 hours" and "silver 25-72 hour"? A case control study. World J
AC C
Emerg Surg 2014;9:60.
7- Gutt CN, Encke J, Köninger J, Harnoss JC, Weigand K, Kipfmüller K, el al. Acute cholecystitis: Early versus delayed cholecystectomy, a multicenter randomized trial (ACDC Study, NCT00447304). Ann Surg 2013;258(3):385-93. 8- Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H et al. TG13 diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:35-46.
12
ACCEPTED MANUSCRIPT 9- Fitzgibbons RJ, Tseng A, Wang H, Ryberg A, Nquyen N, Sims KL. Acute cholecystitis: does the clinical diagnosis correlate with the pathological diagnosis? Surg Endosc, 1996 ;10:1180-4.
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10- Shinke G, Noda T, Hatano H, Shimizu J, Hirota M, Takada A et al. Feasibility and Safety of Urgent Laparoscopic Cholecystectomy for Acute Cholecystitis After 4 Days from Symptom Onset. J Gastrointest Surg 2015;19(10):1787-93.
SC
11- Karamanos E, Sivrikoz E, Beale E, Chan L, Inaba K, Demetriades D. Effect of diabetes on outcomes in patients undergoing emergent cholecystectomy for acute
M AN U
cholecystitis. World J Surg 2013;37(10) :2257-64.
12- Zhu B, Zhang Z, Wang Y, Gong K, Lu Y, Zhang N. Comparison of laparoscopic cholecystectomy for acute cholecystitis within and beyond 72 h of symptom onset during emergency admissions. World J Surg 2012;36(11):2654-8.
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13- Brooks KR, Scarborough JE, Vaslef SN, Shapiro ML. No need to wait: An analysis of the timing of cholecystectomy during admission for acute cholecystitis
EP
using the American College of Surgeons National Surgical Quality Improvement
AC C
Program database. J Trauma Acute Care Surg 2013;74(1):167-74.
ACCEPTED MANUSCRIPT Table 1 : Preoperative characteristics of patients, ICG versus ECG.
ICG (N=143)
ECG (N=350)
P
Age
53.45±13.5
54.22±14.73
Ns
Sex (Male)
22.37%
30%
Diabets
7.69%
19.71%
Hypertension
26.57%
28.85%
Duration of symptoms (Days)
0.7±0.38
2.8±1.4
Temperature (°C)
37.8±0.65
Muscle rigidity
24.47%
White blood cell count (x 109/l)
RI PT
Total population (N=493)
Ns
M AN U
SC
0.001
Ns
<10-3
Ns
32.28%
Ns
11.63±4.21
12.37±4
Ns
Pericholecystic exudate
3.49%
4.28%
Ns
Thickning of the gallbladder wall (mm)
4.32±1.24
4.53±1.53
Ns
AC C
EP
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37.93±0.58
ACCEPTED MANUSCRIPT Table 2 : Peroperative finding and postoperative outcomes, ICG versus ECG.
ICG (N=143)
ECG (N=350)
P
Gangrenous cholecystitis
14%
25.43%
0.005
Conversion
6.29%
13.43%
0.023
Abdominal drainage
59.44%
74.85%
0.001
Overall complications
3.5%
3.48%
Ns
Specific complications
1.4%
1.7%
Ns
Bile duct injury
0%
Reoperations
0.7%
Mortality
0%
SC M AN U
Ns
1.4%
Ns
0%
Ns
2.61±1.19
4.76±1.87
<10-3
125.85±53.44
234±63.23
<10-3
AC C
EP
Direct medical costs (TND)
0.28%
TE D
Total hospital stay (Days)
RI PT
Total population (N=493)
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset ? A retrospective cohort study. -There were significantly more severe forms of acute cholecystitis
RI PT
(moderate/gangrenous) in patients operated 25-72 h following symptom onset compared to patients operated within 24 h following symptom onset.
-Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
SC
of symptoms, significantly reduced conversion to open surgery.
- Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
postoperative complications.
M AN U
of symptoms, significantly reduced total hospital stay without increasing
- Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
AC C
EP
TE D
of symptoms, significantly reduced direct medical costs.
S1743-9191(15)01367-9
DOI:
10.1016/j.ijsu.2015.11.049
Reference:
IJSU 2356
To appear in:
International Journal of Surgery
Received Date: 1 November 2015 Revised Date:
16 November 2015
Accepted Date: 24 November 2015
Please cite this article as: Bouassida M, Hamzaoui L, Mroua B, Chtourou MF, Zribi S, Mighri MM, Touinsi H, Should acute cholecystitis be operated in the 24 hours following symptom onset? A retrospective cohort study, International Journal of Surgery (2015), doi: 10.1016/j.ijsu.2015.11.049. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset ? A retrospective cohort study. Mahdi Bouassida (1), Lamine Hamzaoui (2), Bassem Mroua (1), Mohamed Fadhel
RI PT
Chtourou (1), Slim Zribi (1), Mohamed Mongi Mighri (1), Hassen Touinsi (1) 1- Department of surgery ; Mohamed Tahar Maamouri Hospital ; Nabeul ; Tunisia. 2 : Department of gastroenterology ; Mohamed Tahar Maamouri Hospital ; Nabeul ;
SC
Tunisia.
M AN U
Corresponding author :
Dr Bouassida Mahdi: postal address: 8000 Mrazga, Nabeul, Tunisia. Email: [email protected]
AC C
EP
TE D
Telephone: 001626680963. Fax: 001672285683.
1
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset? A retrospective cohort study. Abstract
RI PT
Background: Early laparoscopic cholecystectomy is the gold standard for management of acute cholecystitis (AC). Nevertheless, the definition used for early phase remained unclear. We aimed to compare the clinical outcome and cost of
SC
immedite (patients undergoing laparoscopic cholecystectomy within 24 h following symptom onset) versus early laparoscopic cholecystectomy (patients managed 25-72
M AN U
h following symptom onset) for acute cholecystitis.
Methods : A retrospective analysis was performed. The outcomes of 143 patients undergoing laparoscopic cholecystectomy within 24 h (ICG) were compared to 350 patients managed 25-72 h following symptom onset (ECG) for acute cholecystitis.
TE D
Results : There were significantly more diabetic patients in the early laparoscopic group (ECG). All other characteristics were comparable (demographic, clinical,
EP
biologic and ultrasonographic characteristics) between the two groups. The rate of conversion to open surgery was significantly higher in the ECG. Overall post
AC C
operative morbidity and specific morbidity did not differ significantly between the groups. Total hospital stay was longer in the ECG. Direct medical costs were higher in the ECG.
Conclusions : Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset of symptoms, significantly reduced conversion to open surgery and total hospital stay without increasing postoperative complications.
2
ACCEPTED MANUSCRIPT Key words: acute cholecystitis ; laparoscopy ; immediate cholecystectomy ; early
AC C
EP
TE D
M AN U
SC
RI PT
cholecystectomy ; conversion ; morbidity.
3
ACCEPTED MANUSCRIPT Introduction Laparoscopic cholecystectomy is the gold standard for the management of acute cholecystitis (AC) [1]. Randomized controlled trials and meta-analyses had shown the
RI PT
benefits of early surgery compared with delayed cholecystectomy with respect to hospital stay and costs, with no significant difference in morbidity and mortality [2,3,4,5]. Nevertheless, the definition used for early phase was unclear because timing of surgery was expressed relative to differing events, such as symptom onset
SC
[6] and time of admission [7]. The aim of this study was to compare the outcomes of
M AN U
patients undergoing laparoscopic cholecystectomy (LC) within 24 h of symptom onset
AC C
EP
TE D
with patients managed 25 to 72 h after symptom onset for AC.
4
ACCEPTED MANUSCRIPT Materials and methods: A retrospective analysis was performed. The outcomes of patients undergoing laparoscopic cholecystectomy within 24 h (ICG) were compared with patients
RI PT
operated 25-72 h following symptom onset (ECG) for acute cholecystitis. The diagnosis and assessment of acute cholecystitis were performed in accordance with the diagnostic criteria of the Revised Tokyo Guidelines published in 2013 [8].
SC
Pathologic diagnoses were made using current standard definitions and criteria used in surgical pathology literature, with similar definitions described by Fitzgibbons et al.
M AN U
in their review [9]. All patients were placed on intravenous antibiotics upon admission which was not continued after surgery. All surgeries in this study were performed by experienced attending surgeons. Laparoscopic cholecystectomy was carried out using three incisions (3 port laparoscopic cholecystectomy technique) with
TE D
pneumoperitoneum installed via a sub-umbilical mini-laparotomy with a maximum intraabdominal pressure at 12 mmHg.
The patients were divided into two groups: the immediate cholecystectomy group
EP
(ICG) and the early cholecystectomy group (ECG). We analyzed and compared the
AC C
clinical features and surgical outcomes of the two groups, including gender, age, comorbidities, severity of acute cholecystitis, WBC count, ultrasonographic findings, conversion to open surgery, presence of postoperative complications, and postoperative hospital stay length. Primary endpoints included the rates of conversion to open surgery and postoperative
complications.
Secondary
endpoints
postoperative hospital stay and direct medical costs.
included
the
length
of
5
ACCEPTED MANUSCRIPT This work was fully compliant with the STROBE criteria. Statistical analysis was conducted using the Fisher’s exact test and the X2 test for categorical data, and the independent t test was used for continuous data. Results
RI PT
are expressed as mean ± standard deviation (SD). Statistical significance was defined as a p value of 0.05. All statistical analyses were performed using SPSS for
AC C
EP
TE D
M AN U
SC
Windows, version 19.0 (SPSS, Chicago, IL, USA).
Results
6
ACCEPTED MANUSCRIPT Between
January
2005
and
January
2013,
646
patients
underwent
cholecystectomies for AC at the Department of Surgery, Mohamed Tahar Maamouri Hospital of Nabeul; 493 of these patients in whom laparoscopic cholecystectomy was performed were considered to be enrolled in the study. Patients treated more than 3
RI PT
days after symptom onset (120 patients) and patients with alternate diagnoses of choledocholithiasis or gallstone pancreatitis (33 patients), were excluded. All patients were operated in the admission day.
SC
There were 137 men and 356 women aged 19– 93 years (mean, 53 years).
M AN U
According to the 2013 Revised Tokyo Guidelines, acute cholecystitis severity was classified as mild (n=258), moderate (n=231), and severe (n=4). One hundred forty three patients were managed within 24 h of symptom onset (the immediate cholecystectomy group ICG), while, 350 patients were managed 25-72 h following symptom onset (the early cholecystectomy group ECG). The demographic
TE D
characteristics of the groups are summarized in Table 1. There were significantly more diabetic patients in the ECG. In the ICG and the ECG, the mean days from symptom onset to surgery were 0.7±0.38 days and 2.8±1.4 days, respectively
EP
(p<103). All other characteristics were comparable (demographic, clinical, biologic
AC C
and ultrasonographic characteristics). The rate of gangrenous cholecystitis was significantly higher in the ECG (25.43% vs. 14% in the ICG; p=0.005). The rate of conversion to open surgery was also significantly higher in the ECG (13.43% vs. 6.29% in ICG, p=0.023). The reasons for conversion consisted of inability to define anatomy in the Calot’s triangle (45 cases), necessity to explore the common bile duct (5 cases), or bleeding (6 cases). Prophylactic drainage was required in 59.44% of cases in the ICG and in 74.85% of cases in the ECG (p=0.001).
7
ACCEPTED MANUSCRIPT Overall postoperative morbidity (3.5% in the ICG vs.3.48 in the ECG; p=0.97) and specific morbidity (1.4% in the ICG vs.1.7 in the ECG; p=0.7) did not differ significantly between the groups. The specific complications in the ICG were bile leak in 2 patients. Six specific complications, including two patients with bile leak, one
RI PT
patient with bile duct injury, two patients with intraabdominal infection and one patient with wound infection were recorded in the ECG. The rate of reoperations did not differ significantly between the groups (0.7% in the ICG vs. 1.4% in the ECG; p=0.9).
SC
No mortality occurred in either group. The total hospital stay was significantly longer in the ECG (4.76±1.87 days vs. 2.61±1.19 days in the ICG; p<10-3). The direct
AC C
EP
TE D
TND in the ICG; p<10-3) (table 2).
M AN U
medical costs were significantly higher in the ECG (234±63.23 TND vs. 125.85±53.44
Discussion
8
ACCEPTED MANUSCRIPT Nowadays, laparoscopic cholecystectomy is the gold standard for the management of acute cholecystitis (AC) [1]. Current data suggest that early LC for acute cholecystitis is superior to late or delayed LC [10], but the definition for early phase was unclear because the timing of surgery was expressed relative to different events,
RI PT
such as symptom onset and time of admission. In 2013, the Tokyo Guidelines were revised, stating that it was better to perform cholecystectomy within 72 h of symptom onset. In this study, “early” was defined with respect to symptom onset; early
SC
cholecystectomy was performed within a time interval of 72 h, the so called golden 72 h [8]. The aim of this study was to compare the outcomes of patients with AC
M AN U
operated within 24 h of symptom onset (immediate laparoscopic cholecystectomy ICG) to those operated 25-72 h following symptom onset (early laparoscopic cholecystectomy ECG). The ICG and ECG were comparable with regard to age, gender, clinical, biological and ultrasonographic characteristics, but there were
TE D
significantly more diabetic patients in the ECG: a possible explanation would be the altered response to inflammation in diabetic patients resulting in a delay in medical
EP
consultation in these patients [11].
In our experience, the time from symptom onset correlates well with the grade of
AC C
severity: gangrenous cholecystitis were significantly more frequent in the ECG. The progression of local inflammation that occurs in the gallbladder over several days leads to hardening of gallbladder wall, loss of normal layered architecture and oedema in the surrounding structures, resulting in an increased rate of conversion to open surgery. In fact, the conversion rate was significantly higher in the ECG. Surgical dissection within this critical period, therefore, appears easier due to lack of surrounding inflammatory resections [12]. This is also reflected in the lower rates of complication and converse to open surgery in the ICG. To the best of our knowledge,
9
ACCEPTED MANUSCRIPT only one previous study compared outcomes of patients undergoing laparoscopic cholecystectomy within 24 h to those of patients managed 25-72 h following symptom onset for acute cholecystitis [6]. Unlike the present study, the previous study did not find any significant difference between the groups in conversion rates. This might be
patients in each group) [6].
RI PT
due to a type II statistical error in that study with a relatively small size of cohorts (35
In agreement with previous studies, there were no significant differences in the rates
between
the
two
groups
[6,10].
Immediate
SC
morbidity
laparoscopic
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cholecystectomy significantly reduced total hospital stay without increasing intra- and postoperative complications [13]. As the ICG reduced medical costs, this is crucial especially for a country with limited resources such as Tunisia. These results are consistent with those reported in a recent multicenter randomized trial which revealed that the costs associated with delayed laparoscopic treatment were approximately
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50 % higher than those associated with early surgery because of longer total hospital stay [12].
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Limitations : This study is limited by the retrospective study design but it was impossible to randomize patients because we defined the two groups from symptom
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onset to surgery and laparoscopic cholecystectomy was carried out on the date of hospital admission.
In conclusion, laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset of symptoms, significantly reduced the rate of conversion to open surgery and the total hospital stay without increasing intra- and postoperative complications. The Author Disclosure Statement: nothing.
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References 1- Bouassida M, Charrada H, Feidi B, Chtourou MF, Sassi S, Mighri MM et al. Could the Tokyo guidelines on the management of acute cholecystitis be adopted in
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ACCEPTED MANUSCRIPT developing countries? Experience of one center. Surg Today 2015 (Article in press). DOI 10.1007/s00595-015-1207-2. 2- Lo CM, Liu CL, Fan ST, Lai EC,Wong J. Prospective randomized study of early
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versus delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 1998;227:461-7.
3- Lau H, Lo CY, Patil NG, Yuen WK. Early versus delayed-interval laparoscopic
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cholecystectomy for acute cholecystitis: A metaanalysis. Surg Endosc 2006;20:82-7. 4- Shikata S, Noguchi Y, Fukui T. Early versus delayed cholecystectomy for acute
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cholecystitis: A meta-analysis of randomized controlled trials. Surg Today 2005;35:553-60.
5- Gurusamy K, Samraj K, Gluud C, Wilson E, Davidson BR.
Metaanalysis of
randomized controlled trials on the safety and effectiveness of early versus delayed
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laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 2010;97:141-50. 6- Ambe P, Weber SA, Christ H, Wassenberg. Cholecystectomy for acute How time-critical are
the
so called "golden 72 hours"?
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cholecystitis.
Or better "golden 24 hours" and "silver 25-72 hour"? A case control study. World J
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Emerg Surg 2014;9:60.
7- Gutt CN, Encke J, Köninger J, Harnoss JC, Weigand K, Kipfmüller K, el al. Acute cholecystitis: Early versus delayed cholecystectomy, a multicenter randomized trial (ACDC Study, NCT00447304). Ann Surg 2013;258(3):385-93. 8- Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H et al. TG13 diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci 2013;20:35-46.
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ACCEPTED MANUSCRIPT 9- Fitzgibbons RJ, Tseng A, Wang H, Ryberg A, Nquyen N, Sims KL. Acute cholecystitis: does the clinical diagnosis correlate with the pathological diagnosis? Surg Endosc, 1996 ;10:1180-4.
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10- Shinke G, Noda T, Hatano H, Shimizu J, Hirota M, Takada A et al. Feasibility and Safety of Urgent Laparoscopic Cholecystectomy for Acute Cholecystitis After 4 Days from Symptom Onset. J Gastrointest Surg 2015;19(10):1787-93.
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11- Karamanos E, Sivrikoz E, Beale E, Chan L, Inaba K, Demetriades D. Effect of diabetes on outcomes in patients undergoing emergent cholecystectomy for acute
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cholecystitis. World J Surg 2013;37(10) :2257-64.
12- Zhu B, Zhang Z, Wang Y, Gong K, Lu Y, Zhang N. Comparison of laparoscopic cholecystectomy for acute cholecystitis within and beyond 72 h of symptom onset during emergency admissions. World J Surg 2012;36(11):2654-8.
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13- Brooks KR, Scarborough JE, Vaslef SN, Shapiro ML. No need to wait: An analysis of the timing of cholecystectomy during admission for acute cholecystitis
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using the American College of Surgeons National Surgical Quality Improvement
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Program database. J Trauma Acute Care Surg 2013;74(1):167-74.
ACCEPTED MANUSCRIPT Table 1 : Preoperative characteristics of patients, ICG versus ECG.
ICG (N=143)
ECG (N=350)
P
Age
53.45±13.5
54.22±14.73
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Sex (Male)
22.37%
30%
Diabets
7.69%
19.71%
Hypertension
26.57%
28.85%
Duration of symptoms (Days)
0.7±0.38
2.8±1.4
Temperature (°C)
37.8±0.65
Muscle rigidity
24.47%
White blood cell count (x 109/l)
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Total population (N=493)
Ns
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0.001
Ns
<10-3
Ns
32.28%
Ns
11.63±4.21
12.37±4
Ns
Pericholecystic exudate
3.49%
4.28%
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Thickning of the gallbladder wall (mm)
4.32±1.24
4.53±1.53
Ns
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37.93±0.58
ACCEPTED MANUSCRIPT Table 2 : Peroperative finding and postoperative outcomes, ICG versus ECG.
ICG (N=143)
ECG (N=350)
P
Gangrenous cholecystitis
14%
25.43%
0.005
Conversion
6.29%
13.43%
0.023
Abdominal drainage
59.44%
74.85%
0.001
Overall complications
3.5%
3.48%
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Specific complications
1.4%
1.7%
Ns
Bile duct injury
0%
Reoperations
0.7%
Mortality
0%
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Ns
1.4%
Ns
0%
Ns
2.61±1.19
4.76±1.87
<10-3
125.85±53.44
234±63.23
<10-3
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Direct medical costs (TND)
0.28%
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Total hospital stay (Days)
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Total population (N=493)
ACCEPTED MANUSCRIPT Should acute cholecystitis be operated in the 24 hours following symptom onset ? A retrospective cohort study. -There were significantly more severe forms of acute cholecystitis
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(moderate/gangrenous) in patients operated 25-72 h following symptom onset compared to patients operated within 24 h following symptom onset.
-Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
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of symptoms, significantly reduced conversion to open surgery.
- Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
postoperative complications.
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of symptoms, significantly reduced total hospital stay without increasing
- Laparoscopic cholecystectomy, for acute cholecystitis, during the first 24 h of onset
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of symptoms, significantly reduced direct medical costs.