Surgical versus endoscopic treatment of bile duct stones

Abstract

Background: Between 10% to 18% of people undergoing cholecystectomy for gallstones have common bile duct stones. Treatment of the bile duct stones can be conducted as open cholecystectomy plus open common bile duct exploration or laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC + LCBDE) versus pre- or post-cholecystectomy endoscopic retrograde cholangiopancreatography (ERCP) in two stages, usually combined with either sphincterotomy (commonest) or sphincteroplasty (papillary dilatation) for common bile duct clearance. The benefits and harms of the different approaches are not known.

Objectives: We aimed to systematically review the benefits and harms of different approaches to the management of common bile duct stones.

Search methods: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7 of 12, 2013) in The Cochrane Library, MEDLINE (1946 to August 2013), EMBASE (1974 to August 2013), and Science Citation Index Expanded (1900 to August 2013).

Selection criteria: We included all randomised clinical trials which compared the results from open surgery versus endoscopic clearance and laparoscopic surgery versus endoscopic clearance for common bile duct stones.

Data collection and analysis: Two review authors independently identified the trials for inclusion and independently extracted data. We calculated the odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) using both fixed-effect and random-effects models meta-analyses, performed with Review Manager 5.

Main results: Sixteen randomised clinical trials with a total of 1758 randomised participants fulfilled the inclusion criteria of this review. Eight trials with 737 participants compared open surgical clearance with ERCP; five trials with 621 participants compared laparoscopic clearance with pre-operative ERCP; and two trials with 166 participants compared laparoscopic clearance with postoperative ERCP. One trial with 234 participants compared LCBDE with intra-operative ERCP. There were no trials of open or LCBDE versus ERCP in people without an intact gallbladder. All trials had a high risk of bias.There was no significant difference in the mortality between open surgery versus ERCP clearance (eight trials; 733 participants; 5/371 (1%) versus 10/358 (3%) OR 0.51;95% CI 0.18 to 1.44). Neither was there a significant difference in the morbidity between open surgery versus ERCP clearance (eight trials; 733 participants; 76/371 (20%) versus 67/358 (19%) OR 1.12; 95% CI 0.77 to 1.62). Participants in the open surgery group had significantly fewer retained stones compared with the ERCP group (seven trials; 609 participants; 20/313 (6%) versus 47/296 (16%) OR 0.36; 95% CI 0.21 to 0.62), P = 0.0002.There was no significant difference in the mortality between LC + LCBDE versus pre-operative ERCP +LC (five trials; 580 participants; 2/285 (0.7%) versus 3/295 (1%) OR 0.72; 95% CI 0.12 to 4.33). Neither was there was a significant difference in the morbidity between the two groups (five trials; 580 participants; 44/285 (15%) versus 37/295 (13%) OR 1.28; 95% CI 0.80 to 2.05). There was no significant difference between the two groups in the number of participants with retained stones (five trials; 580 participants; 24/285 (8%) versus 31/295 (11%) OR 0.79; 95% CI 0.45 to 1.39).There was only one trial assessing LC + LCBDE versus LC+intra-operative ERCP including 234 participants. There was no reported mortality in either of the groups. There was no significant difference in the morbidity, retained stones, procedure failure rates between the two intervention groups.Two trials assessed LC + LCBDE versus LC+post-operative ERCP. There was no reported mortality in either of the groups. There was no significant difference in the morbidity between laparoscopic surgery and postoperative ERCP groups (two trials; 166 participants; 13/81 (16%) versus 12/85 (14%) OR 1.16; 95% CI 0.50 to 2.72). There was a significant difference in the retained stones between laparoscopic surgery and postoperative ERCP groups (two trials; 166 participants; 7/81 (9%) versus 21/85 (25%) OR 0.28; 95% CI 0.11 to 0.72; P = 0.008.In total, seven trials including 746 participants compared single staged LC + LCBDE versus two-staged pre-operative ERCP + LC or LC + post-operative ERCP. There was no significant difference in the mortality between single and two-stage management (seven trials; 746 participants; 2/366 versus 3/380 OR 0.72; 95% CI 0.12 to 4.33). There was no a significant difference in the morbidity (seven trials; 746 participants; 57/366 (16%) versus 49/380 (13%) OR 1.25; 95% CI 0.83 to 1.89). There were significantly fewer retained stones in the single-stage group (31/366 participants; 8%) compared with the two-stage group (52/380 participants; 14%), but the difference was not statistically significantOR 0.59; 95% CI 0.37 to 0.94).There was no significant difference in the conversion rates of LCBDE to open surgery when compared with pre-operative, intra-operative, and postoperative ERCP groups. Meta-analysis of the outcomes duration of hospital stay, quality of life, and cost of the procedures could not be performed due to lack of data.

Authors' conclusions: Open bile duct surgery seems superior to ERCP in achieving common bile duct stone clearance based on the evidence available from the early endoscopy era. There is no significant difference in the mortality and morbidity between laparoscopic bile duct clearance and the endoscopic options. There is no significant reduction in the number of retained stones and failure rates in the laparoscopy groups compared with the pre-operative and intra-operative ERCP groups. There is no significant difference in the mortality, morbidity, retained stones, and failure rates between the single-stage laparoscopic bile duct clearance and two-stage endoscopic management. More randomised clinical trials without risks of systematic and random errors are necessary to confirm these findings.

Conflict of interest statement

None known.

Figures

1

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

3

Study flow diagram.

4

Trial sequential analysis of mortality (open surgery versus endoscopic retrograde cholangio pancreatography)
 The diversity‐adjusted required information size (DARIS) was calculated to 24,498 patients, based on the proportion of patients in the control group with the outcome of 2.79%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 729 participants in eight trials, only 2.98% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional statistical boundaries (dotted red line) have also not been crossed by the cumulative Z‐curve.

5

Trial sequential analysis of morbidity (open surgery versus endoscopic retrograde cholangio pancreatography (ERCP))
 The diversity‐adjusted required information size (DARIS) was calculated to 3,145 patients, based on the proportion of patients in the control group with the outcome of 18.72%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 729 participants in eight trials, only 23.18% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve (blue line) does not cross the trial sequential monitoring boundaries (red line) or the conventional boundaries (etched red line). This is consistent with absence of current evidence of any significant difference between open surgery and ERCP but significantly increased or decreased morbidity of open surgery compared to ERCP cannot be ruled out.

6

Trial sequential analysis of retained stones (open surgery versus endoscopic retrograde cholangio pancreatography (ERCP))
 The diversity‐adjusted required information size (DARIS) was calculated to 3,803 patients, based on the proportion of patients in the control group with the outcome of 15.88%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 609 participants in seven trials, only 16.01% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve (blue line) does not cross the trial sequential monitoring boundaries (red line) but crosses the conventional boundaries (etched red line). This suggests that although there is a statistically significant reduction in the proportion of people with retained stones in the open surgery group compared to the ERCP group, there is a high risk of random error and one cannot firmly conclude that open surgery has significantly lower retained stones proportion compared to the ERCP group.

7

Trial sequential analysis of mortality (laparoscopic common bile duct exploration versus pre‐operative endoscopic retrograde cholangio pancreatography after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 71,546 patients, based on the proportion of patients in the control group with the outcome of 1.02%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 580 participants in five trials, only 0.81% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional statistical boundaries (etched red line) have also not been crossed by the cumulative Z‐curve.

8

Trial sequential analysis of morbidity (laparoscopic common bile duct exploration (LCBDE) versus pre‐operative endoscopic retrograde cholangio pancreatography (ERCP) after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 4,990 patients, based on the proportion of patients in the control group with the outcome of 12.54%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 580 participants in five trials, only 11.62% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve (blue line) does not cross the trial sequential monitoring boundaries (red line) or the conventional boundaries (etched red line). This is consistent with absence of current evidence of any significant difference between LCBDE and ERCP but significantly increased or decreased morbidity of LCBDE compared to ERCP cannot be ruled out.

9

Trial sequential analysis of retained stones (laparoscopic common bile duct exploration versus pre‐operative endoscopic retrograde cholangio pancreatography after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 6,098 patients, based on the proportion of patients in the control group with the outcome of 10.51%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 580 participants in five trials, only 9.51% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve does not cross the trial sequential monitoring boundaries (red line) or the conventional boundaries (etched red line). This is consistent with absence of current evidence of any significant difference between LCBDE and ERCP but significantly increased or decreased proportion of people with retained stones of LCBDE compared to ERCP cannot be ruled out.

10

Trial sequential analysis of mortality (laparoscopic common bile duct exploration versus post‐operative endoscopic retrograde cholangio pancreatography after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 71,546 patients, based on the proportion of patients in the control group with the outcome of 1.02%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 166 participants in two trials, only 0.24% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional statistical boundaries (etched red line) have also not been crossed by the cumulative Z‐curve.

11

Trial sequential analysis of morbidity (laparoscopic common bile duct exploration versus post‐operative endoscopic retrograde cholangio pancreatography after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 4,381 patients, based on the proportion of patients in the control group with the outcome of 14.12%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 166 participants in two trials, only 3.79% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional statistical boundaries (etched red line) have also not been crossed by the cumulative Z‐curve (blue line).

12

Trial sequential analysis of retained stones (laparoscopic common bile duct exploration (LCBDE) versus post‐operative endoscopic retrograde cholangio pancreatography (ERCP) after laparoscopic cholecystectomy)
 The diversity‐adjusted required information size (DARIS) was calculated to 7,661 patients, based on the proportion of patients in the control group with the outcome of 24.71%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 166 participants in two trials, only 2.17% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. The cumulative Z‐curve (blue line) crosses the conventional boundaries (etched red line). This suggests that although there is statistically significant reduction in the proportion of people with retained stones in the LCBDE group compared to the post‐operative ERCP group, there is a high risk of random error and one cannot firmly conclude that LCBDE has significantly lower retained stones proportion compared to the post‐operative ERCP group. The random‐effects model also did not reveal significant difference between the groups.

13

Trial sequential analysis of mortality (single‐stage versus two‐stage procedures)
 The diversity‐adjusted required information size (DARIS) was calculated to 86,456 patients, based on the proportion of patients in the control group with the outcome of 0.79%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 746 participants in seven trials, only 0.86% of the DARIS has been reached. Accordingly, the trial sequential analysis does not show the required information size and the trial sequential monitoring boundaries. As shown, the conventional boundaries have also not been crossed by the cumulative Z‐curve.

14

Trial sequential analysis of morbidity (single‐stage versus two‐stage procedures)
 The diversity‐adjusted required information size (DARIS) was calculated to 4,837 patients, based on the proportion of patients in the control group with the outcome of 12.89%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 0%. After accruing a total of 746 participants in seven trials, only 15.42% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve (blue line) does not cross the trial sequential monitoring boundaries (red line) or the conventional boundaries (etched red line). This is consistent with absence of current evidence of any significant difference between single‐stage and two‐stage procedures but significantly increased or decreased morbidity of single‐stage compared to two‐stage procedures cannot be ruled out.

15

Trial sequential analysis of retained stones (single‐stage versus two‐stage procedures)
 The diversity‐adjusted required information size (DARIS) was calculated to 9,003 patients, based on the proportion of patients in the control group with the outcome of 13.68%, a relative risk reduction of 20%, an alpha of 5%, a beta of 20%, and a diversity of 49.85%. To account for zero event groups, a continuity correction of 0.01 was used in the calculation of the cumulative Z‐curve (blue line). After accruing a total of 746 participants in seven trials, only 8.29% of the DARIS has been reached. So, the futility area was not drawn. The cumulative Z‐curve does not cross the trial sequential monitoring boundaries (red line) but crosses the conventional boundaries (etched red line). This suggests that although there is statistically significant reduction in the proportion of people with retained stones in the single‐stage group compared to the two‐stage group, there is a high risk of random error and one cannot firmly conclude that single‐stage group has significantly lower retained stones proportion compared to the two‐stage group.

1.1. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 1 Mortality.

1.2. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 2 Mortality (Sensitivity analysis).

1.3. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 3 Total morbidity.

1.4. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 4 Morbidity (Sensitivity analysis).

1.5. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 5 Retained stones.

1.6. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 6 Retained stones (Sensitivity analysis).

1.7. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 7 Failure of procedure.

1.9. Analysis

Comparison 1 Open surgery versus ERCP, Outcome 9 Cost.

2.1. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 1 Mortality.

2.2. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 2 Mortality (Sensitivity analysis).

2.3. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 3 Total morbidity.

2.4. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 4 Morbidity (Sensitivity analysis).

2.5. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 5 Retained stones.

2.6. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 6 Retained stones (Sensitivity analysis).

2.7. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 7 Failure of procedure.

2.8. Analysis

Comparison 2 LC + LCBDE versus pre‐operative ERCP + LC, Outcome 8 Conversion to open surgery.

3.1. Analysis

Comparison 3 LC + LCBDE versus LC + intra‐operative ERCP, Outcome 1 Morbidity.

3.2. Analysis

Comparison 3 LC + LCBDE versus LC + intra‐operative ERCP, Outcome 2 Retained stones.

3.3. Analysis

Comparison 3 LC + LCBDE versus LC + intra‐operative ERCP, Outcome 3 Failure of procedure.

3.4. Analysis

Comparison 3 LC + LCBDE versus LC + intra‐operative ERCP, Outcome 4 Conversion to open surgery.

3.5. Analysis

Comparison 3 LC + LCBDE versus LC + intra‐operative ERCP, Outcome 5 Duration of procedure.

4.1. Analysis

Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 1 Total morbidity.

4.2. Analysis

Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 2 Retained stones after primary intervention.

4.3. Analysis

Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 3 Failure of procedure.

4.4. Analysis

Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 4 Conversion to open surgery.

5.1. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 1 Mortality.

5.2. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 2 Mortality (Sensitivity analysis).

5.3. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 3 Morbidity.

5.4. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 4 Morbidity (Sensitivity analysis).

5.5. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 5 Retained stones.

5.6. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 6 Retained stones (Sensitivity analysis).

5.7. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 7 Failure to complete the procedure.

5.8. Analysis

Comparison 5 Single‐stage versus two‐stage management, Outcome 8 Conversion to open surgery.