Early Versus Late Drainage Removal in Patients Who Underwent Pancreaticoduodenectomy: A Comprehensive Systematic Review and Meta-analysis of Randomized Controlled Trials Using Trial Sequential Analysis

Abstract

Background: The superiority of early drain removal (EDR) versus late (LDR) after pancreaticoduodenectomy (PD) has been demonstrated only in RCTs.

Methods: A meta-analysis was conducted using a random-effects model and trial sequential analysis. The critical endpoints were morbidity, redrainage, relaparotomy, and postoperative pancreatic fistula (CR-POPF). Hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), and readmission rates were also evaluated. Risk ratios (RRs) and mean differences (MDs) with a 95% confidence interval (CI) were calculated. Type I and type II errors were excluded, comparing the accrued sample size (ASS) with the required sample size (RIS). When RIS is superior to ASS, type I or II errors can be hypothesized.

Results: ASS was 632 for all endpoints except DGE and PPH (557 patients). The major morbidity (RR 0.55; 95% CI 0.32-0.97) was lower in the EDR group. The CR-POPF rate was lower in the EDR than in the LDR group (RR 0.50), but this difference is not statistically significant (95% CI 0.24-1.03). The RIS to confirm or exclude these results can be reached by randomizing 5959 patients. The need for percutaneous drainage, relaparotomy, PPH, DGE, and readmission rates was similar. The related RISs were higher than ASS, and type II errors cannot be excluded. LOS was shorter in the EDR than the LDR group (MD - 2.25; 95% CI - 3.23 to - 1.28). The RIS was 567, and type I errors can be excluded.

Conclusions: EDR, compared with LDR, is associated with lower major morbidity and shorter LOS.

Keywords: Pancreatic fistula; Pancreatic surgery; Prophylactic drainages.

Fig. 1

Major morbidity; A: forest plot; B: the x-axis is the number of patients yet to be randomized; the y-axis is the cumulative Z-score value representing the effect of each arm; the blue line is the cumulative Z-score obtained by combining the studies; and the dotted red horizontal lines are the conventional boundaries (P value < 0.05); when the Z-curve crosses the conventional boundaries, and the required information size (RIS) is not reached, the result is a false positive (type I error); when the Z-curve does not cross the conventional boundaries and RIS is not reached, the result is a false negative (type II error); the dotted black near-logarithmic lines are the monitoring boundaries; when the Z-curve crosses the monitoring boundaries, the result is a true positive; the inverse dotted black lines are the futility boundaries (area in which any further randomization is useful); EDR early drain removal, LDR late drain removal, RR risk ratio, RIS required information size

Fig. 2

Clinically relevant POPF; A: forest plot; B: the x-axis is the number of patients yet to be randomized; the y-axis is the cumulative Z-score value representing the effect of each arm; the blue line is the cumulative Z-score obtained cumulating the studies; and the dotted red horizontal lines are the conventional boundaries (P value < 0.05); when the Z-curve crosses the conventional boundaries, and the required information size (RIS) is not reached, the result is a false positive (type I error); when the Z-curve does not cross the conventional boundaries and RIS is not reached, the result is a false negative (type II error); the dotted black near-logarithmic lines are the monitoring boundaries; when the Z-curve crosses the monitoring boundaries, the result is a true positive; the inverse dotted black lines are the futility boundaries (area in which any further randomization is useful); EDR early drain removal, LDR late drain removal, RR risk ratio, RIS required information size

Fig. 3

Length of stay; A: forest plot; B: the x-axis is the number of patients yet to be randomized; the y-axis is the cumulative Z-score value representing the effect of each arm; the blue line is the cumulative Z-score obtained combining the studies; and the dotted red horizontal lines are the conventional boundaries (P value < 0.05); when the Z-curve crosses the conventional boundaries, and the required information size (RIS) is not reached, the result is a false positive (type I error); when the Z-curve does not cross the conventional boundaries and RIS is not reached, the result is a false negative (type II error); the dotted black near-logarithmic lines are the monitoring boundaries; the result is a true positive when the Z-curve crosses the monitoring boundaries. The inverse dotted black lines are the futility boundaries (area in which any further randomization is helpful); EDR early drain removal, LDR late drain removal, MD mean difference, RIS required information size