Vascular Resection in Robotic Pancreaticoduodenectomy for Pancreatic Cancer

1. Introduction Pancreaticoduodenectomy, commonly known as the Whipple procedure, was first described in 1935. Since then, it has become the standard surgical treatment for pancreatic head cancer. It is well established that curative resection with negative microscopic margins (R0 resection) is crucial for long-term survival. Unfortunately, fewer than 20% of patients present with resectable disease at diagnosis, as approximately 50% have distant metastases and 30-40% present with borderline resectable or locally advanced disease due to tumor involvement of major vessels such as the superior mesenteric vein (SMV), portal vein (PV), or superior mesenteric artery (SMA). Nevertheless, vascular involvement does not necessarily preclude curative surgery. In selected cases, pancreatic resection with en bloc resection of the PV-SMV confluence can achieve R0 resection. The first report of pancreaticoduodenectomy with PV-SMV resection was published by Moore, et al. in 1951[10]. Despite its technical feasibility, vascular resection (VR) remains a challenging extension to an already complex operation. It is often associated with increased perioperative morbidity and mortality, particularly in cases of extensive vascular involvement or when performed in low-volume centers. Moreover, the long-term survival benefit and likelihood of achieving R0 resection with VR continue to be subjects of ongoing debate. Recent advancements in chemotherapy and increased surgical expertise have led to more patients being considered eligible for curative resection, including those with borderline resectable or locally advanced disease previously deemed inoperable. Consequently, VR has gained wider acceptance and is now supported by expert consensus as a standard approach for pancreatic cancer with local vascular involvement.

   Pancreaticoduodenectomy remains one of the most technically demanding abdominal operations, requiring careful identification of complex vascular structures, meticulous dissection, and precise reconstruction, and, therefore, carrying a significant risk of surgical morbidity and mortality. Traditionally performed via an open approach, open pancreaticoduodenectomy (OPD), this operation is associated with significant postoperative pain, prolonged recovery, and large abdominal incisions. More recently, the advent of the da Vinci Robotic Surgical System (Intuitive Surgical®, Sunnyvale, CA, USA) has expanded the scope of minimally invasive surgery, including robotic pancreaticoduodenectomy (RPD). This platform offers enhanced dexterity, superior ergonomics, and improved visualization, which are particularly valuable for performing intricate dissections, suturing, and vascular reconstructions. While RPD presents unique challenges for VR compared to OPD, it also offers potential benefits such as reduced blood loss, less delayed gastric emptying, faster recovery, and improved cosmetic outcomes. In other words, providing it is done at high-volume centers, RPD is usually considered as safe as OPD, with some advantages in perioperative outcomes.

   Currently, the experience with VR in RPD remains limited, primarily due to a lack of large-scale studies. This study aimed to evaluate the feasibility and clinical justification of VR in the context of RPD for pancreatic cancer. To minimize selection bias, a comparison was conducted between patients undergoing RPD with and without VR, using propensity score matching (PSM) based on ten potential confounding variables related to surgical technique and survival outcomes. To date, this represents the first PSM-based study evaluating VR in RPD from a single high-volume center.

2. Materials and Methods 2.1. Study population and design Data for this propensity score-matched comparative study were obtained from a prospectively maintained database comprising 679 cases of RPD performed between July 2014 and August 2024. This study focused exclusively on patients with pancreatic head adenocarcinoma. The research was retrospectively registered. In accordance with the Declaration of Helsinki, the research registration number was x, and it was registered at Chinese Clinical Trial Registry (ChiCTR), with a hyperlink to the registry entry by https://www.chictr.org.cn. The study protocol was approved by the Institutional Review Board (IRB) of Taipei Veterans General Hospital (IRB-TPEVGH No.: 2025-06-008BC). Informed consent was waived due to the retrospective and anonymized nature of the study. Patient selection for RPD was based on individual preference following detailed counseling regarding the benefits and risks of the robotic approach. Exclusion criteria included severe intra-abdominal adhesions and extensive vascular encasement exceeding 2 cm. In Taiwan, patients are responsible for the cost of robotic instruments, and RPD scheduling depends on the availability of the robotic system. Patients undergoing RPD for pancreatic cancer were categorized into two groups: those with VR and those without. Perioperative data, including demographic information, operative outcomes, pathological findings, and survival details, were prospectively collected and stored in the computer database for use in this propensity score-matched analysis.

2.2. Study endpoints This study aimed to evaluate the feasibility and justification of VR in RPD for pancreatic cancer. The primary study endpoint was to compare the surgical outcomes between patients undergoing VR (+) and VR (-) in RPD using PSM to minimize selection bias and allow for balanced comparisons. The secondary study endpoint was to assess the impact of VR on oncological outcomes and overall survival in patients with pancreatic cancer undergoing RPD.

2.3. Propensity score matching (PSM) strategy PSM was employed to reduce selection bias and facilitate equitable comparisons of treatment effects between the VR (+) and VR (-) groups in RPD. Individual propensity scores were calculated using logistic regression based on ten potential confounding variables related to surgical techniques and survival outcomes: (1) body mass index (BMI), (2) pancreatic parenchymal texture, (3) pancreatic duct diameter, (4) American Society of Anesthesiologists physical status (ASA-PS), (5) tumor size, (6) lymph node involvement, (7) perineural invasion, (8) lymphovascular invasion, (9) tumor differentiation, and (10) disease stage. Patients in the VR (+) and VR (-) groups were matched in a 1:1 ratio using nearest-neighbor matching based on the closest propensity scores. A caliper width of 0.05 standard deviations of the logit of the estimated propensity score was applied to ensure that observed differences in surgical and survival outcomes were attributable to the surgical intervention rather than baseline imbalances in prognostic factors.

2.4. Surgical technique All RPD procedures were performed by the same experienced pancreatic surgical team, led by senior surgeons Dr. Shyr Y.M. and Dr. Wang S.E. The da Vinci® Si or Xi system (Intuitive Surgical Inc., Sunnyvale, CA, USA) was used for all cases. The surgical technique was consistent across the cohort, with the only difference being the inclusion or exclusion of VR. Vascular reconstruction was performed using a continuous 5-0 Prolene suture. Open conversion through a 10-15 cm upper midline incision was undertaken in cases where technical difficulty arose during VR. Pancreatic reconstruction was carried out using the modified Blumgart pancreaticojejunostomy technique, as previously described in our published studies. In brief, patients were positioned supine with legs apart in the reverse Trendelenburg position. Temporary vascular cross-clamping of the superior mesenteric artery (SMA), superior mesenteric vein (SMV), and portal vein (PV) was performed using laparoscopic bulldog clamps (Aesculap Inc., Center Valley, PA, USA), controlled by the robotic ProGrasp Forceps™. Pancreatic duct stents were not routinely used, but soft silicone internal stents were selectively placed in cases with a non-dilated pancreatic duct. The final anastomosis, a hand-sewn gastrojejunostomy, was performed extracorporeally through a 3-6 cm umbilical incision, which also served as the extraction site for the surgical specimen. According to the Brescia consensus classification, this approach constitutes a type I combined robotic/open procedure.[20] Adjuvant chemotherapy was routinely administered within three months postoperatively, regardless of cancer stage, whenever the patient's condition permitted.

2.5. Definitions of surgical complications Postoperative pancreatic fistula (POPF) was defined as clinically relevant grade B or C, according to the 2016 revised grading system by the International Study Group on Pancreatic Fistula (ISGPF). Delayed gastric emptying (DGE), post-pancreatectomy hemorrhage (PPH), and chyle leak were classified based on the definitions established by the International Study Group of Pancreatic Surgery (ISGPS). The radicality of resection was categorized into three groups based on resection margin status: R0 resection, no gross or microscopic tumor within >1 mm of the resection margin; R1 resection, macroscopically negative but microscopically positive margin, with tumor cells present \<1 mm from the margin; R2 resection, gross residual tumor at the resection margin. Surgical mortality was defined as any death occurring within 90 days postoperatively, including deaths during the initial hospitalization or any subsequent readmission. Postoperative complications were graded according to the Clavien-Dindo classification system.

2.6. Statistical analysis Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Categorical variables were expressed as absolute numbers and percentages, and compared using Pearson's chi-squared test or Fisher's exact test, as appropriate. Continuous variables were presented as median (range) or mean±standard deviation (SD), depending on data distribution. Group comparisons for continuous variables were conducted using the two-tailed Student's t-test for normally distributed data, and the Wilcoxon rank-sum test for non-normally distributed data. Overall survival was defined as the time from pancreatic resection to death from any cause or last follow-up. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. All tests were two-sided, and a p-value of \< 0.05 was considered statistically significant.