Abstract
RATIONALE: Postoperative pancreatic fistula (POPF) is a common and serious complication following pancreaticoduodenectomy. Duct-to-mucosa pancreaticojejunostomy has been used in many centers to reconstruct pancreatic digestive continuity following pancreatoduodenectomy. There is currently uncertainty about the benefits and harms of duct-to-mucosa pancreaticojejunostomy. This is an update of a Cochrane review first published in 2022 with three new studies added. OBJECTIVES: To evaluate the benefits and harms of duct-to-mucosa pancreaticojejunostomy versus other types of pancreaticojejunostomy for the reconstruction of pancreatic digestive continuity in people undergoing pancreaticoduodenectomy, and to compare the effects of different duct-to-mucosa pancreaticojejunostomy techniques. SEARCH METHODS: We searched CENTRAL, MEDLINE, two other databases and three trials registers, together with reference checking, and contacted study authors to identify studies for inclusion in the review. The latest search date was 8 June 2024. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) in adults (aged ≥ 18 years) undergoing pancreaticoduodenectomy that compared duct-to-mucosa pancreaticojejunostomy with other types of pancreaticojejunostomy (e.g. invagination pancreaticojejunostomy, binding pancreaticojejunostomy). We also included RCTs that compared different types of duct-to-mucosa pancreaticojejunostomy in adults undergoing pancreaticoduodenectomy. We excluded quasi-randomized studies and non-randomized studies. OUTCOMES: Our critical outcomes were rate of POPF, postoperative mortality, and adverse events. Important outcomes were rate of surgical re-intervention, rate of postoperative bleeding, overall rate of surgical complications, and length of hospital stay. RISK OF BIAS: We used the Cochrane RoB 1 tool to assess the risk of bias in RCTs. SYNTHESIS METHODS: We performed meta-analysis for each outcome using the random-effects model where possible. We assessed the certainty of the evidence using GRADE. INCLUDED STUDIES: We included 14 RCTs with a total of 2140 adult participants undergoing open pancreaticoduodenectomy, of which three RCTs with 444 participants are new to this update. Twelve RCTs involving 1678 participants compared duct-to-mucosa pancreaticojejunostomy (N = 834) with invagination pancreaticojejunostomy (N = 844). Two RCTs involving 462 participants compared duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique (N = 225) with duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique (N = 237). The studies were conducted in North America, Europe, Asia, and Africa and were published between 2003 and 2023. All studies were at overall high risk of bias. SYNTHESIS OF RESULTS: Duct-to-mucosa versus any other type of pancreaticojejunostomy We considered the certainty of the evidence to be very low for all outcomes, downgraded mainly due to high risk of bias, inconsistency, imprecision, and indirectness. Duct-to-mucosa pancreaticojejunostomy may have little to no effect on the rate of POPF (grade B or C; risk ratio [RR] 1.24, 95% confidence interval [CI] 0.72 to 2.14; 9 studies, 1325 participants), postoperative mortality (RR 1.05, 95% CI 0.59 to 1.86; 12 studies, 1675 participants), rate of surgical re-intervention (RR 1.43, 95% CI 0.87 to 2.33; 11 studies, 1552 participants), rate of postoperative bleeding (RR 1.06, 95% CI 0.69 to 1.63; 11 studies, 1478 participants), overall rate of surgical complications (RR 1.10, 95% CI 0.95 to 1.26; 8 studies, 1071 participants), and length of hospital stay (mean difference [MD] -0.41 days, 95% CI -1.87 to 1.04; 4 studies, 658 participants) compared with invagination pancreaticojejunostomy, but the evidence is very uncertain. The studies did not report adverse events. One type of duct-to-mucosa pancreaticojejunostomy versus another type of duct-to-mucosa pancreaticojejunostomy We considered the certainty of the evidence to be very low for all outcomes, downgraded mainly due to high risk of bias and imprecision. Duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique may have little to no effect on the rate of POPF (RR 1.19, 95% CI 0.68 to 2.08; 2 studies, 446 participants), postoperative mortality (RR 2.77, 95% CI 0.55 to 13.98; 2 studies, 446 participants), rate of adverse events (RR 1.04, 95% CI 0.54 to 2.00; 1 study, 236 participants), rate of surgical re-intervention (RR 2.01, 95% CI 0.83 to 4.91; 2 studies, 446 participants), rate of postoperative bleeding (RR 1.43, 95% CI 0.83 to 2.44; 2 studies, 446 participants), overall rate of surgical complications (RR 1.10, 95% CI 0.80 to 1.51; 1 study, 210 participants), and length of hospital stay (MD -2.62 days, 95% CI -6.76 to 1.52; 1 study, 236 participants) compared with duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique, but the evidence is very uncertain. AUTHORS' CONCLUSIONS: For the comparison of duct-to-mucosa versus invagination pancreaticojejunostomy for adult participants undergoing open pancreaticoduodenectomy, duct-to-mucosa pancreaticojejunostomy may have little to no effect on any of the outcomes compared with invagination pancreaticojejunostomy, including rate of POPF (grade B or C), postoperative mortality, rate of surgical re-intervention, rate of postoperative bleeding, overall rate of surgical complications, and length of hospital stay, but the evidence is very uncertain. For the comparison of duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique versus duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique for adult participants undergoing open pancreaticoduodenectomy, data for all outcomes were sparse, and the certainty of the evidence is very low. We are thus unable to draw any conclusions about the effects of duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique. The benefit of duct-to-mucosa pancreaticojejunostomy over other types of pancreaticojejunostomy remains unclear. From a clinical perspective, there is no high-certainty evidence of one type of duct-to-mucosa pancreaticojejunostomy being superior to other types of pancreaticojejunostomy, and hence surgeons should use their preferred techniques. Patients must be informed regarding this uncertainty and the experience of surgeons in the different methods, and be involved in decision-making. FUNDING: This Cochrane review was funded by the National Natural Science Foundation of China (Grant No. 81701950, 82172135), Natural Science Foundation of Chongqing (Grant No. CSTB2025NSCQ-GPX1128), Suitable Technology Promotion Project of Chongqing (Grant No. 2024jstg028), Joint Project of Pinnacle Disciplinary Group, and the Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University. REGISTRATION: Registration (2019): CRD42020169007 Protocol (2019): DOI 10.1002/14651858.CD013462 Original review (2022): DOI 10.1002/14651858.CD013462.pub2.