Early versus delayed laparoscopic cholecystectomy for acute cholecystitis

Kurinchi Selvan Gurusamy; Kumarakrishnan Samraj

doi:10.1002/14651858.CD005440.pub2

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Figure 1

Funnel plot ‐ Bile duct injury

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Figure 2

Funnel plot ‐ Bile leak requiring ERCP

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Figure 3

Funnel plot ‐ Intra‐abdominal collections requiring drainage

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Figure 4

Funnel Plot ‐ Superficial Infection

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Figure 5

Funnel Plot ‐ Deep Infection

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Figure 6

Funnel plot ‐ Conversions

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Analysis 1.1

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 1 Bile duct injury.

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Analysis 1.2

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 2 Bile leak requiring ERCP.

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Analysis 1.3

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 1.4

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 4 Superficial infection.

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Analysis 1.5

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 5 Deep infection.

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Analysis 1.6

Comparison 1 Early versus delayed LC (number of people randomised), Outcome 6 Conversion to open cholecystectomy.

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Analysis 2.1

Comparison 2 Early versus delayed LC (number of people operated), Outcome 1 Bile duct Injury.

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Analysis 2.2

Comparison 2 Early versus delayed LC (number of people operated), Outcome 2 Bile leak requiring ERCP.

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Analysis 2.3

Comparison 2 Early versus delayed LC (number of people operated), Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 2.4

Comparison 2 Early versus delayed LC (number of people operated), Outcome 4 Superficial infection.

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Analysis 2.5

Comparison 2 Early versus delayed LC (number of people operated), Outcome 5 Deep infection.

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Analysis 2.6

Comparison 2 Early versus delayed LC (number of people operated), Outcome 6 Conversion to open cholecystectomy.

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Analysis 3.1

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 1 Bile duct injury.

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Analysis 3.2

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 2 Bile leak requiring ERCP.

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Analysis 3.3

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 3.4

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 4 Superficial infection.

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Analysis 3.5

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 5 Deep infection.

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Analysis 3.6

Comparison 3 Early versus delayed LC ‐ risk difference, Outcome 6 Conversion to open cholecystectomy.

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Analysis 4.1

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 1 Bile duct injury.

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Analysis 4.2

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 2 Bile leak requiring ERCP.

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Analysis 4.3

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 4.4

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 4 Superficial infection.

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Analysis 4.5

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 5 Deep infection.

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Analysis 4.6

Comparison 4 Early versus delayed LC (high‐quality trials), Outcome 6 Conversion to open cholecystectomy.

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Analysis 5.1

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 1 Bile duct injury.

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Analysis 5.2

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 2 Bile leak requiring ERCP.

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Analysis 5.3

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 5.4

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 4 Superficial infection.

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Analysis 5.5

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 5 Deep infection.

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Analysis 5.6

Comparison 5 Early (< 4 days of onset of symptoms) versus delayed LC, Outcome 6 Conversion to open cholecystectomy.

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Analysis 6.1

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 1 Bile duct injury.

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Analysis 6.2

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 2 Bile leak requiring ERCP.

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Analysis 6.3

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 6.4

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 4 Superficial infection.

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Analysis 6.5

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 5 Deep infection.

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Analysis 6.6

Comparison 6 Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC, Outcome 6 Conversion to open cholecystectomy.

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Analysis 7.1

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 1 Bile duct injury.

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Analysis 7.2

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 2 Bile leak requiring ERCP.

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Analysis 7.3

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 3 Intra‐abdominal collections requiring percutaneous drainage.

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Analysis 7.4

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 4 Superficial Infection.

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Analysis 7.5

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 5 Deep infection.

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Analysis 7.6

Comparison 7 Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies), Outcome 6 Conversion to open cholecystectomy.

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Table 1. Common bile duct stones

Study	Surgeon's experience	Early group	Delayed group	Treatment	Per‐operative cholangiogram	Notes
Davila 1999	Not given.	0	2	'Resolved at the same operation' ‐ No further details given.	Not mentioned.
Johansson 2003	Minimum 25 laparoscopic cholecystectomies.	5	3	Laparoscopic common bile duct exploration. Post‐op ERCP.	Yes.	One patient in each group had to be converted to open common bile duct exploration because of large common bile duct stones.
Kolla 2004	Surgical consultant.	0	0	Not applicable.	No.	Co‐existing common bile duct stones were exclusion criteria.
Lai 1998	Minimum 50 laparoscopic cholecystectomies.	0	0	Not applicable.	No.	Co‐existing common bile duct stones were exclusion criteria.
Lo 1998	More than 300 laparoscopic cholecystectomies.	0	0	Preoperative selective ERCP.	No.
ERCP = endoscopic retrograde cholangio‐pancreatography

Table 1. Common bile duct stones

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Table 2. Conversion and bile duct injury rates (Based on people who underwent surgery)

Study	Conversion‐ELC	Conversion ‐DLC	Conversion‐crossover	Bile duct injury‐ELC	Bile duct injury‐DLC
Davila 1999	1/27 (3.7%)	6/36 (16.7%)	4/5 (80%)	0/27 (0%)	1/36 (2.8%)
Johansson 2003	23/74 (31.1%)	20/69 (29%)	10/18 (55.5%)	0/74 (0%)	1/69 (1.4%)
Kolla 2004	5/20 (25%)	5/20 (25%)	Not applicable.	1/20 (5%)	0/20 (0%)
Lai 1998	11/53 (20.8%)	11/46 (23.9%)	2/8 (25%)	0/53 (0%)	0/46 (0%)
Lo 1998	5/48 (10.4%)	9/45 (20%)	2/9 (22.2%)	0/48 (0%)	1/45 (2.2%)
All studies	45/222 (20.3%)	51/216 (23.6%)	18/40 (45%)	1/222 (0.5%)	3/216 (1.4%)
ELC = early laparoscopic cholecystectomy DLC = delayed laparoscopic cholecystectomy

Table 2. Conversion and bile duct injury rates (Based on people who underwent surgery)

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Table 3. Odds ratio and risk difference (95% Confidence intervals)

Outcome	Fixed, ITT	Random, ITT	Fixed/available case	Random/available case	Good quality, fixed	"Zero", Kt+Kc=1 (Sweeting 2004)	"Zero", Kt+Kc=0.1 (Sweeting 2004)	"Zero", Kt+Kc=0.01 (Sweeting 2004)	Risk difference
Bile duct injury	0.63 [0.15, 2.70]	0.61 [0.12, 3.07]	0.61 [0.14, 2.62]	0.59 [0.12, 2.98]	0.70 [0.14, 3.63]	1.47 [0.32, 6.70]	1.12 [0.09, 13.50]	1.02 [0.07, 15.91]	‐0.01 [‐0.03, 0.02]
Bile leak requiring ERCP	5.78 [1.00, 33.29]	5.03 [0.83, 30.48]	5.55 [0.96, 31.94]	4.82 [0.80, 29.21]	5.78 [1.00, 33.29]	1.91 [0.57, 6.40]	17.3 [0.76, 391.37]	171.2 [0.01, 2494435.29]	0.03 [0.00, 0.06]
Intra‐abdominal collections requiring drainage	1.86 [0.56, 6.18]	1.91 [0.55, 6.63]	1.91 [0.62, 5.88]	1.85 [0.53, 6.41]	2.34 [0.60, 9.19]	Not applicable	Not applicable	Not applicable	0.02 [‐0.01, 0.05]
Superficial infections	1.39 [0.56, 3.44]	1.38 [0.54, 3.52]	1.33 [0.54, 3.29]	1.32 [0.52, 3.37]	1.24 [0.48, 3.23]	Not applicable	Not applicable	Not applicable	0.01 [‐0.02, 0.05]
Deep infections	0.43 [0.09, 1.98]	0.46 [0.10, 2.22]	0.41 [0.09, 1.88]	0.44 [0.09, 2.12]	0.43 [0.09, 1.98]	0.78 [0.24, 2.62]	0.43 [0.09, 2.08]	0.39 [0.08, 2.02]	‐0.01 [‐0.04, 0.01]
Conversions	0.84 [0.53, 1.34]	0.87 [0.55, 1.4]	0.79 [0.5, 1.25]	0.82 [0.51, 1.31]	0.94 [0.58, 1.51]	Not applicable	Not applicable	Not applicable	‐0.03 [‐0.10, 0.05]
ITT = intention‐to‐treat analysis ERCP = endoscopic retrograde cholangio‐pancreatography

Table 3. Odds ratio and risk difference (95% Confidence intervals)

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Table 4. Heterogeneity

Outcome	Chi‐square test	Higgin's I square
Bile duct injury	0.72	0%
Bile leak requiring ERCP	0.78	0%
Intra‐abdominal collections requiring drainage	0.58	0%
Superficial infections	0.86	0%
Deep infections	0.52	0%
Conversions	0.51	0%
ERCP = endoscopic retrograde cholangio‐pancreatography

Table 4. Heterogeneity

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Table 5. Subgroup analysis (Odds ratio ‐ 95% Confidence intervals)

Outcome	All studies	ELC less than 4 days	ELC (excluding column 3)	Surgical experience 25 to 50 laparoscopic cholecystectomy
Bile duct injury	0.63 [0.15, 2.70]	1.16 [0.15, 8.79]	0.32 [0.03, 3.16]	0.32 [0.01, 7.87]
Bile leak requiring ERCP	5.78 [1.00, 33.29]	3.15 [0.12, 82.16]	7.03 [0.86, 57.69]	7.03 [0.86, 57.69]
Intra‐abdominal collections requiring drainage	1.86 [0.56, 6.18]	1.77 [0.33, 9.53]	2.18 [0.48, 9.90]	4.97 [0.57, 43.14]
Superficial Infections	1.39 [0.56, 3.44]	1.12 [0.19, 6.60]	1.50 [0.52, 4.31]	1.47 [0.40, 5.35]
Deep Infections	0.43 [0.09, 1.98]	Not estimable	0.99 [0.20, 5.00]	0.63 [0.10, 3.88]
Conversions	0.84 [0.53, 1.34]	0.54 [0.18, 1.66]	0.93 [0.56, 1.54]	1.07 [0.61, 1.90]
ELC = early laparoscopic cholecystectomy

Table 5. Subgroup analysis (Odds ratio ‐ 95% Confidence intervals)

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Table 6. Non‐resolving or recurrent cholecystitis

Study	Delayed laparoscopic cholecystectomy	Emergency surgery in delayed group	Emergency surgery in delayed group (%)	Conversion to open cholecystecomy in the emergency surgery in delayed group
Davila 1999	36	5	13.9%	4
Johansson 2003	71	18	25%	10
Kolla 2004	20	0	0%	0
Lai 1998	51	8	15.7%	2
Lo 1998	50	9	18%	2
Total	228	40	17.5%	18

Table 6. Non‐resolving or recurrent cholecystitis

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Table 7. Operating time and hospital stay

Study	Early‐operating time	Delay‐operating time	Early ‐hospital stay	Delay‐hospital stay
	Minutes (Median)	Minutes (Median)	Days (Median)	Days (Median)
Davila 1999	71	50	1.6	2.7
Johansson 2003	98	100	5	8
Kolla 2004	104 (Mean)	93 (Mean)	4.1 (Mean)	10.1 (Mean)
Lai 1998	122.8 (Mean)	106.6 (Mean)	7.6 (Mean)	11.6 (Mean)
Lo 1998	135	105	6	11

Table 7. Operating time and hospital stay

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Comparison 1. Early versus delayed LC (number of people randomised)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	0.63 [0.15, 2.70]

2 Bile leak requiring ERCP Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	5.78 [1.00, 33.29]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	1.86 [0.56, 6.18]

4 Superficial infection Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	1.39 [0.56, 3.44]

5 Deep infection Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 1.98]

6 Conversion to open cholecystectomy Show forest plot	5	451	Odds Ratio (M‐H, Fixed, 95% CI)	0.84 [0.53, 1.34]

Comparison 1. Early versus delayed LC (number of people randomised)

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Comparison 2. Early versus delayed LC (number of people operated)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct Injury Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	0.61 [0.14, 2.62]

2 Bile leak requiring ERCP Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	5.55 [0.96, 31.94]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	1.91 [0.62, 5.88]

4 Superficial infection Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	1.33 [0.54, 3.29]

5 Deep infection Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	0.41 [0.09, 1.88]

6 Conversion to open cholecystectomy Show forest plot	5	438	Odds Ratio (M‐H, Fixed, 95% CI)	0.79 [0.50, 1.25]

Comparison 2. Early versus delayed LC (number of people operated)

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Comparison 3. Early versus delayed LC ‐ risk difference

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	‐0.01 [‐0.03, 0.02]

2 Bile leak requiring ERCP Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	0.03 [0.00, 0.06]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	0.02 [‐0.01, 0.05]

4 Superficial infection Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.02, 0.05]

5 Deep infection Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	‐0.01 [‐0.04, 0.01]

6 Conversion to open cholecystectomy Show forest plot	5	451	Risk Difference (M‐H, Fixed, 95% CI)	‐0.03 [‐0.10, 0.05]

Comparison 3. Early versus delayed LC ‐ risk difference

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Comparison 4. Early versus delayed LC (high‐quality trials)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	0.70 [0.14, 3.63]

2 Bile leak requiring ERCP Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	5.78 [1.00, 33.29]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	2.34 [0.60, 9.19]

4 Superficial infection Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	1.24 [0.48, 3.23]

5 Deep infection Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.09, 1.98]

6 Conversion to open cholecystectomy Show forest plot	4	388	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.58, 1.51]

Comparison 4. Early versus delayed LC (high‐quality trials)

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Comparison 5. Early (< 4 days of onset of symptoms) versus delayed LC

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	1.16 [0.15, 8.79]

2 Bile leak requiring ERCP Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	3.15 [0.12, 82.16]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	1.77 [0.33, 9.53]

4 Superficial infection Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	1.12 [0.19, 6.60]

5 Deep infection Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

6 Conversion to open cholecystectomy Show forest plot	2	103	Odds Ratio (M‐H, Fixed, 95% CI)	0.54 [0.18, 1.66]

Comparison 5. Early (< 4 days of onset of symptoms) versus delayed LC

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Comparison 6. Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.03, 3.16]

2 Bile leak requiring ERCP Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	7.03 [0.86, 57.69]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	2.18 [0.48, 9.90]

4 Superficial infection Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	1.50 [0.52, 4.31]

5 Deep infection Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	0.99 [0.20, 5.00]

6 Conversion to open cholecystectomy Show forest plot	3	348	Odds Ratio (M‐H, Fixed, 95% CI)	0.93 [0.56, 1.54]

Comparison 6. Early (including studies with > 4 days but < 7days of onset of symptoms) versus delayed LC

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Comparison 7. Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Bile duct injury Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.87]

2 Bile leak requiring ERCP Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	7.03 [0.86, 57.69]

3 Intra‐abdominal collections requiring percutaneous drainage Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	4.97 [0.57, 43.14]

4 Superficial Infection Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	1.47 [0.40, 5.35]

5 Deep infection Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	0.63 [0.10, 3.88]

6 Conversion to open cholecystectomy Show forest plot	2	249	Odds Ratio (M‐H, Fixed, 95% CI)	1.07 [0.61, 1.90]

Comparison 7. Early versus delayed LC (surgical experience: 25 to 50 laparoscopic cholecystectomies)

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