Robotic-assisted versus open distal pancreatectomy for benign and low-grade malignant pancreatic tumors: a propensity score-matched study

Minimally invasive distal pancreatectomy was first applied in 1992 [1] and has become increasingly popular in recent years [2, 3]. Robotic-assisted distal pancreatectomy (RDP) and laparoscopic distal pancreatectomy (LDP), as two kinds of minimally invasive surgery for left-side pancreatic tumors, both showed noninferior short-term outcomes and even oncological outcomes in previous studies [4‐6], the newest guideline about minimally invasive pancreas resection, also paid noticeable attention on minimally invasive distal pancreatectomy [7]. While a series of studies have shown the advantages of LDP, a comparison between robotic and open approaches for distal pancreatectomy, especially for benign and low-grade malignant tumors, is lacking.

Patients with benign and low-grade malignant pancreatic tumor patients are always priority candidates for minimally invasive pancreatic surgery. For benign and low-grade malignant tumors in the pancreatic body/tail, LDP has already been proven to have a better postoperative effect than open distal pancreatectomy (ODP).

The surgical treatment of benign and low-grade malignant tumors in the pancreatic body/tail always has the potential for spleen-preserving distal pancreatectomy (SPDP). SPDP is associated with lower rates of postoperative complications [8‐10], such as thrombocytosis, embolism, and infection. Splenic vessel-sacrificing (Warshaw technique (WT)) SPDP and splenic vessel-preserving (Kimura technique (KT)) SPDP are two methods applied in SPDP [11, 12]. Although more technically challenging, the KT has a lower risk of splenic infarction and gastric varices, which could occur with the WT [13‐15].

Therefore, we designed this study with two aims: to compare the short-term outcomes of ODP and RDP for benign and low-grade malignant tumors and to analyze the factors affecting the spleen preservation rate and the use of KT SPDP.

We conducted a retrospective study from a prospective database. This study was performed according to the STROBE guidelines [16]. The study protocol was approved by the Institutional Review Board, Ruijin Hospital, and the requirement for informed consent was waived due to the observational and retrospective nature of the study.

A minimally invasive approach is considered technically available, safe and feasible for DP in the treatment of left-side pancreatic tumors [5, 26‐29]. As an inevitable part of minimally invasive DP, RDP has been frequently analyzed in observational studies, and a series of reports have indicated that RDP results in a shorter operative duration, less blood loss, shorter postoperative hospital stay, higher spleen preservation rate, and comparable morbidity and mortality rates [30‐34].

For patients with benign and low-grade malignant pancreatic tumors, good cosmetic effects are required, and low morbidity and organ preservation should be achieved. To compare the perioperative outcomes of RDP and ODP for such benign and low-grade malignant tumors in the pancreatic body/tail, we performed a retrospective analysis using a prospective database. In our study, we collected data from patients with benign and low-grade malignant tumors treated with RDP after the learning curve had been passed for comparison with data from patients treated with ODP during the same time period. PSM has been a popular statistical method in recent years to eliminate bias in observational studies [35], and PSM was applied in our study to eliminate selection bias caused by baseline population and tumor characteristics, such as age, sex, preoperative ALB level, abdominal surgery history, tumor size, and pathological type. After matching, the equivalence of these baseline indices made the results of the subsequent analysis more robust. A total of 416 cases of RDP and 263 cases of ODP were collected. After 1:1 matching, 219 cases in each group were matched and compared. We found that RDP had advantages in terms of operative duration, estimated blood loss, spleen preservation rate, KT SPDP rate, postoperative surgical site infection rate, and gastrointestinal function recovery. However, postoperative oral intake occurred later in the RDP cohort; this may have been influenced by the different protocols used to determine the postoperative oral intake time between the two cohorts. Altogether, these results reveal that RDP causes less surgical trauma and provides a better foundation for postoperative recovery. The robotic approach has been considered a particularly suitable approach for operations that emphasize meticulous and bloodless dissection, thus potentially expanding the indications for RDP [36, 37]. Studies focusing on RDP and benign and low-grade malignant tumors were separately analyzed, and this series of studies also showed that RDP had noninferior perioperative outcomes when compared with corresponding laparoscopic or open surgery in the treatment of these nonmalignant tumors [33, 38, 39]. These conclusions are in agreement with our results showing that RDP offers acceptable perioperative outcomes for benign and low-grade malignant pancreatic body/tail tumors.

In Guerrini’s study, RDP showed advantages over LDP in terms of the conversion rate (8.2 vs. 21.6%) [40]. In benign cases, a lower conversion rate indicates a better cosmetic effect. In our study, there were 3 cases (0.7%) of conversion to laparotomy in the RDP group, and severe abdominal adhesion and uncontrollable intraoperative bleeding led to conversion in all intraductal papillary mucinous neoplasia (IPMN) cases. In all the benign and low-grade malignant tumor cases, the conversion was always caused by IPMN and inflammatory neoplasms, and the precise dissection and suturing of the robotic system consistently provided better management in potential conversion cases. Moreover, the robotic approach always achieved good cosmetic effects.

SPDP, as an important technique in organ-preserving surgery for pancreatic body/tail nonmalignant tumors, has both hematological and immunological advantages, as proven by a series of studies [11, 12, 41, 42]. The WT is a relatively easy spleen-preserving method, and the spleen can often be vascularized by short gastric vessels and the left gastroepiploic artery. The feasibility and acceptable short-term outcomes of WT SPDP have also been proven in different studies [43, 44]. However, WT SPDP is associated with the risk of splenic infarction [45], and there are still some concerns about the long-term outcomes of the WT, such as gastric varices and the risk of gastric bleeding [46]. KT SPDP is the first choice and preferred method for pancreatic body/tail tumors with spleen preservation potential. After PSM to minimize selection bias, the RDP cohort showed a significantly higher spleen preservation rate and a higher rate of KT SPDP. In the RDP and ODP cohorts, the approaches for pancreatic parenchyma mobilization showed different trends, with a “bottom-up” view in RDP, which was differed from the “top-down” view in ODP. In our clinical practice, the intraoperative bleeding that causes the failure of KT SPDP is often caused by splenic vein bleeding when separating the pancreatic parenchyma from the splenic vessels. Using the robotic surgical system, the 3D view, EndoWrist and tremor elimination all helped to provide more delicate manipulation, precise dissection of the splenic vessels and more meticulous ligation or suturing the small branches of the splenic vessels, which may allow the difficulties in laparoscopic DP with spleen-preserving intention to be better overcome [19]. The advantages of SPDP were reconfirmed by the univariate and multivariate analyses. Age, tumor size, a higher proportion of inflammatory neoplasms and blood loss were independent risk factors of the spleen preservation rate and the KT SPDP rate. Larger tumor size and the nature of the inflammatory neoplasms were often associated with more difficult manipulation of the splenic vessels, and blood loss was often associated with surgical trauma and reflected the difficulty of the procedures. An elevated CA 19-9 level was identified in 44 cases in our study and was found to be an independent predictor of splenic vessel sacrifice (WT SPDP and DP with splenectomy). Elevated CA 19-9 levels have been reported to be associated with acute or chronic pancreatitis even in benign pancreatic tumors [47]. The inflammation caused by some types of benign and low-grade malignant tumors, such as inflammatory neoplasms and IPMN, may increase the level of CA 19-9 and ultimately cause the failure of splenic vessel preservation, which may explain why an elevated CA 19-9 level was an independent risk factor for KT SPDP.

The low morbidity rate, especially the lower rate of severe complications (Clavien–Dindo score ≥ 3), is also crucial in benign and low-grade malignant pancreatic tumors. POPF, as the most common postoperative complication, may cause subsequent intraoperative infection and PPH. The overall POPF rate was 24.2% in the RDP group vs 32.0% in the ODP group, and the corresponding clinically relevant POPF rates (grade B and C) were 14.6% vs 18.7%, respectively, both without a significant difference. In our study, we transected the pancreas with a stapler in most cases; thus, we did not need to address the pancreatic stump. In other cases in which we transected the pancreas with a harmonic scalpel, we always found the pancreatic duct and ligated it with sutures; the robotic system provided an enlarged view and allowed delicate manipulation, which facilitated handling of the pancreatic stump and reduced the POPF rate. The POPF rate in our study is comparable to that in other series of RDP, such as the rate of 17% reported by Gavriilidis in a systematic review and network meta-analysis [48]. PPH, which is a severe complication after DP, always requires reoperation (including intervention). In our initial practice, before we had mastered this approach, massive PPH with hypovolemic shock occurred in three cases of RDP with the KT, and reoperation was performed (including digital subtraction angiography, celiac artery angiography and splenic artery embolization). After passing the learning curve, we performed more precise manipulations of the small branches of the pancreatic transverse and dorsal arteries, and massive PPH seldom occurred.

There were several limitations to this study, which should be noted. Although the PSM method was applied to reduce selection bias, the retrospective nature of the study cannot be ignored. In addition, despite preoperative MDT discussion and performing the operations based on the intention-to-treat principle, some subjective factors still influenced the intraoperative decision, such as inflammation, adhesions and difficulty in mobilizing the splenic vessels, which may influence the surgeon’s choice of the KT, the WT or splenectomy. Third, the follow-up data were missing in some cases, which prevented further analysis of the long-term outcomes between the RDP and ODP groups. Finally, as an irreplaceable minimally invasive pancreatic surgery, LDP also plays an important role in patient treatment, but in our department, since the introduction of the da Vinci robotic system in 2010, many LDP surgeries for benign and low-grade malignant tumors have been replaced by RDP according to our initial experience and that of other surgeons [31, 45]. Therefore, a lack of sufficient clinical data for LDP prevents subsequent comparisons among robotic, laparoscopic and open approaches for DP.

For benign and low-grade malignant tumors in the pancreatic body/tail, the perioperative outcomes of RDP were better than those of ODP in terms of the operative duration, estimated blood loss, spleen preservation, infection rate and gastrointestinal function recovery. The robotic approach was an independent predictor of both spleen preservation and KT SPDP. However, this was a retrospective study with inherent drawbacks. Although we used the PSM method to minimize bias, further randomized controlled studies should be designed to verify the value of RDP for benign and low-grade malignant tumors.