RAMPS was first reported by Strasberg and his associates as a modified form of distal pancreatosplenectomy in 2003 to treat distal pancreatic adenocarcinoma [3]. The main advantages of this procedure include improved visibility, superior control of splenic vessels at the beginning of operation, a more extensive posterior resection margin, and a more lymph node yield. A number of clinicians have subsequently recommended that RAMPS should be the standard surgical procedure for distal pancreatic adenocarcinoma and adopted it in routine clinical practice [6, 13, 14]. Our study reported a large series of patients with distal pancreatic adenocarcinoma who underwent RAMPS as a routine procedure to replace the standard distal pancreatosplenectomy. The data in this study was from our prospective database and analyzed retrospectively.
The Strasberg's procedure has been reported from many centers with markedly different long-term survival outcomes [2, 15–19]. Lee et al [18] reported the highest 5-year OS rate of 56%, and a median OS of 60 months in 12 patients who underwent minimally invasive RAMPS. However, the tumors in that study were all confined to the pancreas, and 75% of patients had a node-negative disease. The largest reported study before our study was by Strasberg and his associates who reported 78 RAMPS with a median and 5-year OS rates of 24.6 months and 25%, respectively [2]. The shortest median OS of 18 months was reported by Chang and his associates and the 5-year OS rate was below 20% [15]. Park and his associates reported a 5-year survival rate of 12%, and their study is the only study which suggested RAMPS to have a better OS rate than distal pancreatosplenectomy [19]. The marked differences in baseline characteristics in patients who underwent RAMPS for distal pancreatic adenocarcinoma in the different studies probably explain the controversial results on the reported long-term survival outcomes.
In the cohort of 354 patients in our study, the median OS was 21.1 months and the 5-year OS rate was 23.1%. These figures were similar to those reported in other studies [5, 13, 16, 19]. The dataset showed no significant differences in OS and DFS between the two groups and posterior RAMPS was not an independent predictive factor of OS on multivariate analysis. The recent study which compared the clinical outcome of two procedures for patients without periadrenal infiltration showed similar consequence[20]. However, as previous studies considered tumor location to be an important prognostic factor for pancreatic cancer[21–23], subgroup analysis was undertaken in this study to find out the impact of the two different operations on long-term survival. For body and tail PDAC, differences in lymphatic drainage and nerve infiltration can affect prognosis in the two anatomical sites. The study by O’Morchoe showed that lymphatics along the superior and inferior borders of the left half of pancreatic body and tail drained to the splenic nodes in the hilum of the spleen or to the gastrosplenic nodes in the gastrosplenic omentum. Lymphatics along the right drained to the gastroduodenal and intrapancreatic lymph nodes [24]. Furthermore, Tsuchikawa et al. [25] found carcinoma of pancreatic body to be frequently accompanied by involvement of extra-pancreatic nerve plexus around the celiac artery and suggested distal pancreatectomy combined with celiac axis resection (DP-CAR) to increase the R0 resection rate.
According to the pancreatic lymphatic system by Deki and Sato[11] the left-side pancreas can be divided into pancreatic body and pancreatic tail subgroups for stratification analysis by drawing a longitudinal line from the point where the splenic vein crosses the upper border of the pancreas to emerge onto the anterior surface of the organ. It is interesting to note the posterior resection margin between anterior and posterior RAMPS is widest in the pancreatic body. The resection margins come closer towards the pancreatic tail. Of 166 patients who had PDAC in the pancreatic body in this study after PSM, posterior RAMPS resulted in significantly better prognosis (Median OS: 25.5 months vs. 18.6 months; P = 0.047), and it was also an independent prognostic factor on multivariate analysis (P = 0.016).
In addition, posterior RAMPS, has, at least, the theoretical advantages over anterior RAMPS in allowing resection of more regional lymphatics around the common hepatic artery and the celiac axis [11], and removing all soft tissues within the triangle formed by the aorta or celiac trunk, the posterior surface of pancreas, and the adrenal gland. This concept of achieving a wide posterior resection margin is similar to the concept of dissecting the ‘mesopancreas’ to include nerves, vessels, lymphatics, and nodes between the pancreatic head and SMA in operations for pancreatic head adenocarcinoma [26], a procedure called pancreaticoduodenectomy with systematic mesopancreas dissection (PD-SMD) [27]. In our center, the area in the left triangle of aorta is routinely cleared in posterior RAMPS for tumors of pancreatic body. Our study showed that posterior RAMPS harvested more lymph nodes in the pancreatic body subgroup (19.6 ± 4.4 vs. 16.1 ± 2.9, P < 0.001), than the pancreative tail subgroup, and it was an independent prognostic factor of long-term survival.
The overall surgical complication rates were 31.8% for the anterior RAMPS group and 30.1% for the posterior RAMPS group, though in the latter group more extensive resections were performed to include resection of adjacent organs or great vessels. The use of RAMPS with combined portal or superior mesenteric venous resection for distal pancreatic adenocarcinoma has been reported to be safe [28]. Our data also showed posterior RAMPS, when compared with anterior RAMPS, resulted in no prolongation in postoperative hospital stay, although intraoperative blood loss was significantly more.
Previous studies on RAMPS using tangential sections (shaved edge sections) showed that adequate and complete assessment of surgical margins to be extremely important in differentiating between R0 with R resections. This technique uses multiple 2- to 3-mm sections which are shaved off from the edges of the sample. The sections are then laid into cassettes with the cut surfaces facing downward. Any tumor present in these sections is interpreted as incomplete excision. However, the disadvantages of this technique are that it is time-consuming and there is no possibility to assess the distance of the tumor to the resection margins, which is especially important when R1 resection of pancreatic cancer is defined using the criterion of 1 mm [29]. Digitalized whole-mount slide images (DWMSIs) method[30] was used in our study to evaluate resection margins, especially the posterior peritoneal resection margins (Supplement Fig. 3). This technique involves the use of a large whole cut surface slice by cross-sectioning tissues of the body and tail. The distance can easily be measured with digital pathological scanning. The additional advantages are that lymphatic, vascular and nerve invasions can be comprehensively evaluated to study the direction, extent, and depth of invasion [31]. This procedure makes our results more reliable.
The current study has the following limitations: (1). As with all retrospective studies, potential biases due to uncontrolled treatment allocation can be present. (2). As our center started neoadjuvant treatment relatively late, few patients underwent neoadjuvant therapy in this dataset. (3). This study is a single-center study and the results may not be applicable to other centers. A well-designed randomized controlled study is needed to provide a high level of medical evidence on RAMPS.