Laparoscopic versus open pancreatoduodenectomy for periampullary tumors: a randomized clinical trial

Abstract

Background: There is a lack of robust evidence on the efficacy of laparoscopic pancreatoduodenectomy compared to open surgery. This study was aimed to compare time to functional recovery (FR) between laparoscopic and open pancreatoduodenectomy.

Materials and methods: This pragmatic, multicenter, randomized controlled phase 3 trial was conducted in seven tertiary centers. Patients with periampullary tumors were randomized using a block design in a 1:1 ratio and stratified by pancreatic fistula risk. Participants were randomized to undergo open or laparoscopic pancreatoduodenectomy by expert pancreatic surgeons. The primary outcome was the time to FR, defined as the number of days until FR was achieved in all five domains. The secondary endpoints included perioperative and short-term oncological outcomes.

Results: Between March 2019 and June 2022, 252 patients were randomly assigned to laparoscopic ( n =125) or open groups ( n =127). Primary outcomes were reported in 235 patients. The mean time to FR was shorter in laparoscopic group compared to the open group (7.7 vs. 9.0 days, P =0.03). Laparoscopic group exhibited a higher cumulative rate of FR compared to the open group (Hazard ratio,1.34; 95% CI, 1.03-1.74; P =0.02). Severe complications, R0 resection, the number of retrieved lymph nodes and short-term survival rates were comparable between the two groups.

Conclusions: Laparoscopic pancreatoduodenectomy demonstrated modest advantages in FR time over open surgery for selected patients with experienced surgeons.

Trial registration: ClinicalTrials.gov NCT03870698.

Figure 1

Screening, enrollment, randomization, and follow-up. The primary outcome was analyzed in 235 patients underwent either laparoscopic or open pancreatoduodenectomy in the modified intention-to-treat analysis, which included all patients who underwent randomization and assigned treatment. Per-protocol analysis was performed in 229 patients who completed the study without deviation of randomization treatment.

Figure 2

Primary end point for cumulative incidence of functional recovery after surgery. Shown are the cumulative incidence curves and Fine-Gray model for achievement of functional recovery 30 days after surgery between laparoscopic and open pancreatoduodenectomy groups. Functional recovery comprised of five domains including pain control, restored mobility, caloric intake, infection, and fluid administration, and achievement of functional recovery was defined as first day of 3 or more consecutive achievement of all domains.

Figure 3

Forest plot for achievement of five domains for functional recovery. Red square of the first line represents point estimates for the instantaneous ratio of functional recovery in patients who underwent laparoscopic pancreatoduodenectomy as compared to patients who underwent open pancreatoduodenectomy. Horizontal lines indicate the associated 95% confidence intervals. Each line indicates five domains which were included functional recovery such as pain control, restored mobility, caloric intake, infection, fluid administration. Especially, restored mobility showed faster in laparoscopic pancreatoduodenectomy group than open group significantly.