Comparison of the Safety and Effectiveness Between Laparoscopic and Open Pancreatoduodenectomy: A Systematic Review and Meta-Analysis

Background: Due to the significant heterogeneity in previous studies, concerns persist regarding the safety and effectiveness of laparoscopic pancreatoduodenectomy (LPD). Therefore, with the publication of new researches, a comprehensive systematic review is needed to evaluate the potential benefits of laparoscopic pancreatoduodenectomy. We aimed to compare safety and effectiveness of laparoscopic and open pancreatoduodenectomy (OPD) from the published studies, and investigate the source of heterogeneity from the surgeons’ and patients’ perspectives.  Methods: We searched PubMed, Cochrane, Embase, and Web of Science databases for relevant studies published before February 1, 2021 comparing laparoscopic and open pancreatoduodenectomy. The database search yielded a total of 6,578 articles, and 81 articles were full-text reviewed. Studies of laparoscopic-assisted surgery were not included. The primary outcome was mortality. Three independent reviewers screened and extracted the data, and resolved disagreements by consensus. Studies were evaluated for quality using ROB2·0 and ROBINS-I. Meta-analyses were conducted in random-effect and fixed-effect models. Different meta-analyses were conducted according to the different designs of the studies. The sensitivity analyses and meta-regression were conducted to explore the source of heterogeneity. This study was registered with PROSPERO, ID CRD42021234579.  Findings: We analyzed 34 studies involving 46,729 patients (4,705 LPD and 42,024 OPD). LPD was associated with lower mortality in overall studies (odds ratio [OR] 0·800, 95% confidence interval [CI] 0·659–0·973, P=0·025, I2=0·0%) and unmatched studies (OR 0·774, 95%CI 0·628–0·954, P=0·017, I2=0·0%). However, no differences in mortality were seen in RCTs (randomized controlled trial) (risk ratio 1·080, 95%CI 0·473–2·466, P=0·854, I2=13·4%) and matched studies (OR 0·904, 95%CI 0·515–1·587, P=0·726, I2=0·0%). Sensitivity analysis found that mortality was also similar between the two groups in elderly patients, patients with pancreatic ductal adenocarcinoma (PDAC), high-volume hospitals, and low-volume hospitals (all P >0·05). However, LPD showed non-inferiority in length of stay (LOS), severe complications, clinical relevant-postoperative pancreatic fistula, clinical relevant-biliary leak, intra-abdominal infection, readmission, overall survival, and 2-year relapse. Elderly patients benefited marginally from LPD, while patients with PDAC and patients in high-volume hospitals benefit significantly. Meta-regression confirmed that baseline differences including the proportion of males, age, proportion of biliary drainage, diagnosis of PDAC, and lesion size between LPD and OPD groups had a significant impact on LOS, severe complications, ICU stay, estimated intraoperative blood loss, and lymph node harvest (all P <0·05).  Interpretation: Our study found no significant difference between LPD and OPD with respect to mortality. LPD should be suggested according to the non-inferiority in LOS, complications, and overall survival. Meanwhile, the elderly patients benefited marginally from LPD, while the patients with PDAC and patients in high-volume hospitals benefit significantly. Funding: National Natural Science Foundation of China and Tongji Hospital, Huazhong University of Science and Technology, China Declaration of Interest: None to declare.