| Figure 1. Risk of bias summary: review authors' judgements about each risk of bias item for each included study. |
| Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies. |
| Figure 3. Study flow diagram. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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). |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Figure 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. |
| Analysis 1.1. Comparison 1 Open surgery versus ERCP, Outcome 1 Mortality. |
| Analysis 1.2. Comparison 1 Open surgery versus ERCP, Outcome 2 Mortality (Sensitivity analysis). |
| Analysis 1.3. Comparison 1 Open surgery versus ERCP, Outcome 3 Total morbidity. |
| Analysis 1.4. Comparison 1 Open surgery versus ERCP, Outcome 4 Morbidity (Sensitivity analysis). |
| Analysis 1.5. Comparison 1 Open surgery versus ERCP, Outcome 5 Retained stones. |
| Analysis 1.6. Comparison 1 Open surgery versus ERCP, Outcome 6 Retained stones (Sensitivity analysis). |
| Analysis 1.7. Comparison 1 Open surgery versus ERCP, Outcome 7 Failure of procedure. |
| Analysis 1.8. Comparison 1 Open surgery versus ERCP, Outcome 8 Hospital stay. |
| Analysis 1.9. Comparison 1 Open surgery versus ERCP, Outcome 9 Cost. |
| Analysis 2.1. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 1 Mortality. |
| Analysis 2.2. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 2 Mortality (Sensitivity analysis). |
| Analysis 2.3. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 3 Total morbidity. |
| Analysis 2.4. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 4 Morbidity (Sensitivity analysis). |
| Analysis 2.5. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 5 Retained stones. |
| Analysis 2.6. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 6 Retained stones (Sensitivity analysis). |
| Analysis 2.7. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 7 Failure of procedure. |
| Analysis 2.8. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 8 Conversion to open surgery. |
| Analysis 2.9. Comparison 2 LC + LCBDE versus pre-operative ERCP + LC, Outcome 9 Duration of hospital stay. |
| Analysis 3.1. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 1 Morbidity. |
| Analysis 3.2. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 2 Retained stones. |
| Analysis 3.3. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 3 Failure of procedure. |
| Analysis 3.4. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 4 Conversion to open surgery. |
| Analysis 3.5. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 5 Duration of procedure. |
| Analysis 3.6. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 6 Duration of hospital stay. |
| Analysis 3.7. Comparison 3 LC + LCBDE versus LC + intra-operative ERCP, Outcome 7 Cost. |
| Analysis 4.1. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 1 Total morbidity. |
| Analysis 4.2. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 2 Retained stones after primary intervention. |
| Analysis 4.3. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 3 Failure of procedure. |
| Analysis 4.4. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 4 Conversion to open surgery. |
| Analysis 4.5. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 5 Duration of procedure. |
| Analysis 4.6. Comparison 4 LC + LCBDE versus LC + postoperative ERCP, Outcome 6 Duration of hospital stay. |
| Analysis 5.1. Comparison 5 Single-stage versus two-stage management, Outcome 1 Mortality. |
| Analysis 5.2. Comparison 5 Single-stage versus two-stage management, Outcome 2 Mortality (Sensitivity analysis). |
| Analysis 5.3. Comparison 5 Single-stage versus two-stage management, Outcome 3 Morbidity. |
| Analysis 5.4. Comparison 5 Single-stage versus two-stage management, Outcome 4 Morbidity (Sensitivity analysis). |
| Analysis 5.5. Comparison 5 Single-stage versus two-stage management, Outcome 5 Retained stones. |
| Analysis 5.6. Comparison 5 Single-stage versus two-stage management, Outcome 6 Retained stones (Sensitivity analysis). |
| Analysis 5.7. Comparison 5 Single-stage versus two-stage management, Outcome 7 Failure to complete the procedure. |
| Analysis 5.8. Comparison 5 Single-stage versus two-stage management, Outcome 8 Conversion to open surgery. |