Background
Distal pancreatectomy is the standard surgical approach for left-sided pancreatic cancer. However, the long-term survival of these patients remains unsatisfactory, with a median survival time of 10–28 months and a 5-year overall survival of 6–30% [
1‐
5]. In recent years, new surgical approaches for resectable or borderline resectable pancreatic cancer, including the artery-first approach [
6‐
9], superior mesenteric vein/portal vein resection and reconstruction [
10‐
13], intraoperative radiotherapy [
14,
15] and preoperative chemo-radiotherapy [
16‐
18], have been increasingly applied to pancreaticoduodenectomy to achieve R0 resection for carcinomas of the head of the pancreas. Despite the highly aggressive nature of the disease and early regional lymph node metastasis, adenocarcinomas of the body and tail of the pancreas have attracted significantly less clinical attention. However, in 2003, Strasberg described a new distal pancreatectomy technique, termed radical antegrade modular pancreatosplenectomy (RAMPS), to achieve negative posterior resection margins and to completely remove the N1 lymph nodes [
19]. In the past decade, the RAMPS procedure has been increasingly applied, particularly in Japan and Korea [
20‐
24]. However, the number of patients eligible for RAMPS is too small to consider any prospective randomized trial of RAMPS versus the standard procedure. Therefore, systemic review and meta-analysis of the current retrospective data comparing RAMPS and the standard procedure are necessary and useful to clarify the role the RAMPS in the treatment of left-sided pancreatic cancer.
Discussion
The RAMPS procedure, first reported in 2003, was designed to establish an operation with oncologic safety both with respect to the dissection planes used to achieve negative margins as well as the extent of lymph node dissection, thereby improving patient outcomes. According to the original paper by Strasberg, if the tumour did not penetrate the posterior capsule of the pancreas on preoperative CT scans, the resection plane lay just behind the anterior renal fascia, and anterior RAMPS was performed; otherwise, posterior RAMPS was applied, and the left adrenal gland and Gerota fascia were removed [
19]. Deep resection is performed because tumours can spread microscopically beyond their radiographically visible or palpable margins. The systemic review of descriptive studies concerning the RAMPS procedure for the treatment of left-sided pancreatic cancer is summarized in Table
4. R0 resection was achieved in 77–100% of patients after RAMPS, and an R0 rate > 85% was observed in most case series. In this meta-analysis, we found that the R0 resection rate was significantly higher in the RAMPS group than in the standard surgery group [89.5% vs 83.6%, OR 95% CI, 2.19 (1.16 ~ 4.13);
P = 0.02]. However, the combined resection rates were comparable between the RAMPS and standard groups [OR 95% CI, 3.30 (1.00 ~ 10.93);
P = 0.05], which might be attributable to the low rate of posterior RAMPS procedures in present practices [
24,
31,
32].
Table 4
Systemic review of descriptive studies about RAMPS procedure in treatment of left-sided pancreatic cancer
| 2003 | 10 | 6/4 | 4(2–15) | NA | 90 | 1–28 | NA | 3(30.0%) | NA | NA |
| 2007 | 23 | 15/8 | 5.1 ± 2.6 | 48 | 87 | 14.3 ± 7.8 | 17 for alive | 11(47.8%) | NA | NA |
| 2010 | 5 | 5/0 | 2.4 ± 0.7 | 20 | 100 | 8.2 ± 5.9 | 13(4–21) | 1(20%) | NA | NA |
| 2011 | 6 | 3/3 | 3.0 ± 0.9 | NA | 100 | NA | NA | NA | NA | NA |
| 2012 | 47 | 32/15 | 4.4 ± 2.1 | 55 | 80.1 | 18.0 ± 11.7 | 26.4 for alive | 27(57.4%) | 25.9 | 35.5 |
| 2012 | 24 | 19/5 | 4.09 ± 2.15 | 70.8 | 91.7 | 20.92 ± 11.24 | 20.06 | 21(87.5%) | 18.2 | NA |
| 2013 | 12 | 12/0 | 2(0.8–4.0) | 50 | NA | 17(5–29) | NA | NA | NA | NA |
| 2013 | 10 | 1/9 | 4.65(1.0–8.0) | 70 | 90 | 17(13–95) | 19.1 ± 10.1 | NA | 20.5% | NA |
| 2014 | 12 | 12/0 | 2.75 ± 1.32 | 25 | 100 | 10.5 ± 7.14 | 39 | 5(41.7%) | 60.0 | 55.6 |
| 2014 | 24 | 19/5 | 3.5 ± 1.4 | 54.2 | 88 | 28 ± 12 | 52 for alive | 10(41.7%) | NA | 53 |
| 2015 | 11 | NA | 3.35(1.9–5.5) | 91 | 77 | 26(9–80) | 12.4(3.5–16.4) | 1(9.1%) | NA | NA |
| 2015 | 49 | NA | 0.5–8.3 | 55 | 83.7 | 15 | 41.4 | 30(61.2%) | 22.6 | 27 |
| 2016 | 78 | 56/22 | 4.71 | 47 | 85 | 20 ± 12.2 | 20.6 (0.3–145.3) | 49(62.8%) | 24.6 | 25.1 |
Lymph node metastasis has been reported to be an independent prognostic risk factor for resected left-sided pancreatic cancer [
33,
34]. The extent of lymph node dissection is one of the key points of pancreatosplenectomy. However, guidelines from Eastern and Western countries differ significantly. In the RAMPS procedure, the lymph nodes along the superior and inferior borders of the left-sided pancreas (No. 10, 11, and 18 according to Japanese classification), the celiac lymph nodes (No. 9) and the nodes along the front and left side of the superior mesenteric artery (No. 14p, 14d) are considered N1 lymph nodes and are completely removed; in the standard operation, only lymph nodes No. 10, 11, and 18 are resected [
35]. Therefore, in this meta-analysis, we found that the number of lymph nodes harvested in the RAMPS procedure was significantly greater than in the standard operation [WMD 95% CI, 7.06 (4.52–9.60);
P < 0.01]. Compared with the standard operation, the RAMPS procedure is reported to require greater technical skill for extensive resection as well as longer operating times [
24,
28]. However, these differences were not detected in our meta-analysis [WMD 95% CI, −16.81 (−95.19–61.57);
P = 0.67]. Additionally, RAMPS procedures were not correlated with longer hospital stays [WMD 95% CI, 0.49 (−2.97–3.94);
P = 0.78]. These findings may be influenced by a recent study with a large volume of patients and more experienced surgeons.
Improving the survival of patients with resectable or borderline resectable tumours is the major aim of the RAMPS procedure. The 5-year survival rate after RAMPS ranged from 25.1% to 55.6% (Table
4). In a recent study, when comparing RAMPS and the standard procedure, RAMPS exhibited a greater tendency towards improvement of median survival times relative to the standard procedure (47 vs 34 months,
P = 0.192), but no significant differences in the recurrence rates were detected (66.6 vs 75.0%;
P = 0.1386) [
20]. In the study by Park, the 5-year overall survival rate was 40.1% in RAMPS patients and 12.0% in the standard group (
p = 0.014). However, by multivariate analysis, adjuvant chemoradiotherapy but not RAMPS reached statistical significance with respect to overall survival [
24]. In the present study, no favourable overall survival outcomes were detected when comparing RAMPS with the standard procedure. The recurrence rate after RAMPS did not decrease (65.7% vs 64.8%,
P = 0.482), which was consistent with our meta-analysis [OR 95% CI, 0.66 (0.40 ~ 1.09);
P = 0.10] and led to similar DFS rates in the two groups [OR 95% CI, 1.02 (0.62 ~ 1.68);
P = 0.93]. With respect to recurrence, we believed that it is important to differentiate local recurrence from systemic recurrence. RAMPS increased the R0 resection rate and theoretically may decrease local recurrence. Unfortunately, few studies reported the local recurrence rate. In these studies, systemic recurrence alone, such as liver, lung and peritoneum, was reported most often, and the local recurrence rate did not decrease significantly after RAMPS [
20,
31].
Recently, a modified RAMPS procedure including a superior mesenteric artery (SMA)-first approach has been attempted [
22,
36‐
38]. The artery-first approach, initially designed for the early determination of cancer resectability during pancreatoduodenectomy, is now applied in the RAMPS procedure. As described by Strasberg, dissection of the SMA is performed after transection of the pancreas or wide detachment of the distal pancreas and spleen, which may reach the point of no return. However, carcinoma of the pancreatic body and tail exhibits high aggressive potential, and the celiac axis (CA) and SMA are often involved. Although left-sided pancreatic cancer with CA invasion can be treated by distal pancreatectomy combined with celiac axis resection (DP-CAR), SMA encroachment usually indicates that the tumour is a late-stage lesion and may be completely unresectable. SMA-first RAMPS provides an opportunity to determine resectability before pancreas transection. Dissection further along the aorta and exposure of the left renal vein and the left adrenal gland can help prepare the correct RAMPS dissection plane in advance. When the renal vein is reached, the surgeon can accurately assess the extent of tumour penetration to help decide whether anterior or posterior RAMPS is optimal. Data from Japan has demonstrated the safety and reliability of this procedure even in borderline resectable tumours [
22,
36,
37].
Laparoscopic or robotic RAMPS operations have also been performed with satisfactory oncological results and survival outcomes [
39‐
41]. However, this procedure is limited to highly selective cases. According to the Yonsei criteria developed by Lee, only patients meeting the following characteristics can be treated with minimally invasive RAMPS: (1) tumour confined to the pancreas, (2) intact fascial layer between the distal pancreas and the left adrenal gland and kidney, and (3) tumour located more than 1–2 cm from the celiac axis [
39].
An important limitation of this review is the small number of included studies and cases. In addition, the nature of the included retrospective studies may lead to allocation and publication biases and could distort the conclusions of this review. However, this study represents the initial attempt to perform a systemic review and meta-analysis of RAMPS versus the standard procedure in the treatment of left-sided pancreatic cancer. Our systematic review and meta-analysis presents evidence to suggest that RAMPS is the optimal procedure to increase R0 resection rates but has no increased benefit with respect to tumour recurrence or patient survival.