Minimally invasive pancreatoduodenectomy: caution is warranted

Minimal invasive surgery is widely accepted to be the preferred operation technique for many indications, because it is associated with less blood loss and pain, faster recovery, shorter hospital stay, and smaller incisions when compared to open surgery. Along with improved short-term results, long-term results seem promising in some oncologic diseases. For example, subgroup analysis of randomized controlled trials has demonstrated that minimal invasive surgery may improve disease-free and overall survival in stage II and III rectal cancer (1). Within the last decade, robot-assisted surgery has been established to further advance minimally invasive surgery results and has evolved as the predominant approach in prostatectomies in some industrialized countries and has been suggested to surpass laparoscopy and open surgery for various indications (2). In general, robotic surgery has advantages because of high-definition three-dimensional (3D) visualization, greater degrees of freedom and range of motion, and the ability to perform highly precise and accurate movements. These issues may be of utmost importance in complex surgery like pancreatoduodenectomy (PD), which includes a technically highly demanding pancreatic anastomosis.

PD is considered to be one of the most complex visceral operations. PD is associated with relevant morbidity and mortality rates, and centralization to high-volume hospitals is needed to improve postoperative outcomes (3). Demanding resection techniques along the superior mesenteric artery and the portomesenteric axis for pancreatic head tumors, in locally progressed cases, eventually combined with vascular resection, are to be managed together with sophisticated reconstruction techniques, including the pancreaticojejunostomy and the hepaticojejunostomy. Undoubtedly, the pancreatic anastomosis is the Achilles’ heel of PD regarding short-term outcome, since clinically relevant postoperative pancreatic fistula (POPF) (grade B and C) is the main contributor to septic complications and mortality (4).

Bruna et al. published just recently on behalf of the International Consortium on Minimally Invasive Pancreatic Surgery (I-MIPS) a cohort study of 6,256 patients who underwent minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD) in 36 referral centers in Europe, South America, and Asia (5). All operations were performed between 2007 and 2020. They focused on 1,139 patients who developed POPF grade B and C. Of those, 336 patients after MIPD were matched to 336 patients after OPD. The authors found that patients after MIPD were more frequently associated with other clinically relevant complications as compared to OPD. Among matched patients who had MIPD and developed POPF, 55% of patients experienced a second clinically relevant complication (as compared to 36% in OPD), 67% had major morbidity Clavien-Dindo grade ≥3 (as compared to 37% in OPD), 21% had postpancreatectomy hemorrhage (PPH, as compared to 8% in OPD, all significantly higher at a P level of <0.001). Likewise, the reoperation rate was higher with 21% compared to 7%, and the length of hospital stay was longer with 27 days as compared to 22 days in OPD (also significantly different at a P level of <0.001). In-hospital and 30-day mortality were not significantly different, with 7.4% and 4.5%, respectively. Numbers on 90-day mortality have not been presented. Remarkably, these differences persisted in a sensitivity analysis that included procedures which were performed in the most recent 5 years (2016–2020). In a subgroup analysis that compared robot-assisted and laparoscopic PD, a similar rate of second clinically relevant complications and PPH was observed, along with a higher rate of delayed gastric emptying grade B/C and a lower rate of reoperations after robot-assisted PD. The length of hospital stay, in-hospital and 30-day mortality showed no significant differences between these groups.

The authors discuss various explanations for this unexpected outcome. Among others, the development of intraabdominal adhesions, which may be more pronounced after open surgery, may play a protective role against severe secondary complications of POPF by restricting the movement of activated and erosive pancreatic enzymes in the abdominal cavity. Reduced adhesion formation might further facilitate drain displacement and the development of undrained intra-abdominal collections. Energy devices that are applied in MIPD are known to be associated with a lateral thermal spread and could jeopardize vascular integrity. Likewise, sealed vessels may be less resistant to the erosive effects of pancreatic fluids as compared to double ligations, transfixing stitches, or metal clips, which are used in open surgery. Furthermore, patient-related factors may contribute to this result, since patients undergoing MIPD are often younger with a better physical performance and have a smaller, benign or premalignant lesion. Their enhanced initial tolerance to complications may delay the identification and adequate treatment of postoperative complications and reduce the chance for timely intervention and rescue. However, the authors state that these explanations represent an initial attempt to discuss the surprising findings of the study.

The publication by Bruna et al. also includes the data of patients who did not develop POPF, of whom 2,543 had undergone MIPD and 2,583 had OPD. A closer look at the data of this unmatched cohort, which is only presented in a table and which is not further described or discussed, reveals higher rates of major morbidity (Clavien-Dindo grade ≥3), chyle leak, and reoperation rates in MIPS as compared to OPD. Likewise, the median length of hospital stay was longer in MIPD, with 15 vs. 12 days in OPD (5). This data is in disagreement with several previous trials and meta-analyses, which presented similar short-term results after MIPD and OPD (6).

One may argue that the major bias of the study is that data of patients has been collected in the period from 2007 to 2020, when most surgeons who performed minimally invasive PD were in their learning curve. However, in a sensitivity analysis that included only procedures which were performed in the most recent 5 years (2016–2020) at these highly experienced centers on MIPD, the findings of more second clinical relevant complications, more major morbidity, a higher rate of PPH, a longer length of hospital stay, and a higher rate of reoperations persisted in patients who developed POPF after MIPD as compared to OPD (5).

Does the study by Bruna et al. change the game, since it included a very large patient cohort that was only treated at highly experienced large-volume centers? Probably not. In experienced hands, randomized controlled trials have proven the safety of MIPD. However, randomized controlled trials on PD have always included selected patients, and even when operations were restricted to experienced surgeons with more than 100 previously performed MIPDs, as it was mandated in the largest multicenter RCT done to date, the benefit in length of hospital stay was marginal (7). Bringing the risks of pancreatic anastomosis into focus, Dokmak et al. presented data that laparoscopic PD should not be considered in the subgroup of patients with a high-risk pancreas for clinically relevant POPF (8). Consequently, a complexity and experience grading system has been established by the International Study Group on Pancreatic Surgery (ISGPS) to optimally select patients according to specific risk factors which are known to influence the complexity of the procedure (9). In this classification system, patient-related risk factors include anatomic (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors. Cutoffs were defined for surgeon and center experience.

Importantly, one must be aware that there are few randomized trials that were prematurely stopped because of safety concerns as a result of higher 90-day mortality in MIPD (10) or that showed increased rates of major pancreas-specific complications in robot-assisted PD (11) as compared to open OPD. These results are in line with a recent nationwide prospective analysis of patients who underwent PD in the Netherlands, which identified laparoscopic or robot-assisted resection as an independent predictor of clinically relevant POPF (12). Probably, MIPD will prevail at very-high volume pancreatic centers with highly specialized surgeons in robot-assisted PD. Whether this technique is suitable for the vast majority of patients, including those with borderline resectable pancreatic head tumors, needs to be defined in future trials. Well-proven longer operative times and higher costs of laparoscopic and robot-assisted PD combined with their limited benefits in short- and long-term outcomes, as known so far, might narrow their general use. Most importantly, analysis of data from large nationwide data sets or of national cancer registries may help to generate valid information about the long-term effects of the various surgical approaches in pancreatic cancer. Unexpected results have previously had severe implications for the use of the minimal invasive approach in cervical carcinoma (13,14) or for transanal total mesorectal excision (TaTME) of rectal cancer (15).

We won’t stop progress in pancreatic surgery, but real caution is needed. MIPD is not for everyone. The robot has increased the number of surgeons who are able to perform the procedure minimally invasively, but it will remain in select hands. When in doubt—open surgery is advised. It should not be a shame to perform PD open!

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-150/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-150/coif). The author has no conflicts of interest to declare.

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