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To assess the published evidence on clinical outcomes following radical antegrade modular pancreatosplenectomy (RAMPS) for adenocarcinoma in the body or tail of the pancreas.
Method
PubMed and Chinese Biomedical Literature databases were searched. The results of comparisons between RAMPS and standard retrograde pancreatosplenectomy (SRPS) were analyzed by meta-analytical techniques.
Results
The literature search identified 13 observational studies involving 354 patients undergoing RAMPS. The overall morbidity and 30-day mortality was 40% and 0% respectively. The R0 resection rate was 88%; the median number of retrieved lymph nodes was 21; and the median 5-year overall survival rate was 37%. The result of meta-analysis showed that RAMPS was associated with a significantly less intraoperative bleeding [weighted mean difference −195.2 (95% confidence interval (CI) −223.27 to −167.13); P < 0.001], a greater number of retrieved lymph nodes [odds ratio (OR) 6.19 (95% CI 3.72 to 8.67); P < 0.001] and a higher percentage of R0 resection [OR 2.46 (95% CI 1.13 to 5.35); P = 0.02] as compared with SRPS.
Conclusion
The current literature provides supportive evidence that RAMPS is a safe and effective procedure for adenocarcinoma in the body or tail of the pancreas, and is oncologically superior to SRPS.
Introduction
Adenocarcinoma in the body or tail of the pancreas is conventionally resected by the standard retrograde pancreatosplenectomy (SRPS) performed in the left-to-right direction with mobilization of the spleen first, and then resection of the posterior aspect of the pancreas from the tail to the body. However, SRPS is associated with a high positive tangential margin rate, devoid of the described lymph node drainage of the organ. To overcome these problems, Strasberg et al.
in 2003 introduced a modified technique of SRPS called radical antegrade modular pancreatosplenectomy (RAMPS) in which division of the neck of the pancreas and splenic vessels and a celiac node dissection are performed first, followed by dissection proceeding from right-to-left in 1 of the 2 posterior dissection planes, depending on the extent of penetration of the tumor. However, only a few studies have reviewed the experience and practice of RAMPS.
Radical antegrade modular pancreatosplenectomy procedure for adenocarcinoma of the body and tail of the pancreas: ability to obtain negative tangential margins.
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
In addition, data comparing this procedure with SRPS are limited, and therefore the potential value of RAMPS has not been clearly demonstrated. The aim of this systematic review was to assess the published evidence on clinical outcomes following RAMPS for adenocarcinoma in the body or tail of the pancreas.
Methods
This study was performed in accordance with the guidelines of preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2009.
Literature search strategy and study identification
An electronic search was performed of the Pubmed and Chinese Biomedical Literature database from the date of the earliest report of RAMPS in 2003 to May 2016 using the following keyword: “radical antegrade modular pancreatosplenectomy.” No language restriction was applied. Reference lists of relevant articles were further searched manually to check for additional studies. Studies reporting the outcomes following the RAMPS in patients with pancreatic adenocarcinoma were included for analysis. To ensure that the series reviewed reflect consistent surgical approach, only study involving more than 5 patients were included in the systematic review of overall outcome of RAMPS. Reviews, conference abstracts, non-human studies, case report were excluded. In cases of duplicated studies with overlapping patients, only the most recent publication with accumulating numbers of patients or increased lengths of follow-up was considered.
Two investigators (YZ and BS) independently appraised each eligible article using predefined criteria. Discrepancies between the two reviewers were resolved by discussion and consensus. Data were extracted on the first author, country, year of publication, sample size, study design, population characteristics, duration of operation, estimated blood loss, proportion of radical (R0) resection, morbidity, incidence and severity of pancreatic fistula as defined by the International Study Group on Pancreatic Fistula (ISGPF),
Descriptive statistics were performed and data are expressed as mean or median (interquartile range) where appropriate. A meta-analysis of the comparative studies of RAMPS and SRPS was undertaken with Review Manager (RevMan) software, version 5.1 (The Cochrane Collaboration, Software Update, Oxford). Odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (95% CI) were calculated for dichotomous variables and continuous variables respectively. Heterogeneity was assessed using the χ2 test and I2. When the heterogeneity was not significant (I2 <50%), a fixed-effects model was used for the pooled analysis. Otherwise, a random-effects model was used. Statistical significance was set at P < 0.05.
Results
Systematic review
As shown in Fig. 1, the literature search initially yielded 41 articles, of which 13 studies comprising a total of 354 patients fulfilling the eligibility criteria were included in this systematic review and are summarized in Table 1.
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
Agreement for these studies was 100% between the two reviewers. No randomised controlled trials (RCT) or meta-analyses were identified. All these studies were observational in nature and classified as level-4 evidence. Five studies were conducted in Japan,
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
The surgical outcomes of the 13 studies are summarized in Table 2. Of the 354 patients, 330 underwent open RAMPS and 24 underwent a laparoscopic or robotic approach. The overall mortality was 0%. Pancreatic fistula, the most critical complication following pancreatectomy, was seen in 70 (20%) patients. Fifty-five pancreatic fistulas were graded according to the ISGPF. Most were grade A (20, 36%) or B (23, 42%); only five (1%) were grade C and seven (13%) were graded as B–C.
Table 2The surgical outcomes of radical antegrade modular pancreatosplenectomy.
Median or mean; BT, blood transfusion; PLN, number of patients with positive lymph nodes; RLN, retrieved lymph nodes; R0 R, R0 resection; MS, median survival; OS, overall survival.
Median or mean; BT, blood transfusion; PLN, number of patients with positive lymph nodes; RLN, retrieved lymph nodes; R0 R, R0 resection; MS, median survival; OS, overall survival.
Median or mean; BT, blood transfusion; PLN, number of patients with positive lymph nodes; RLN, retrieved lymph nodes; R0 R, R0 resection; MS, median survival; OS, overall survival.
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
a Median or mean; BT, blood transfusion; PLN, number of patients with positive lymph nodes; RLN, retrieved lymph nodes; R0 R, R0 resection; MS, median survival; OS, overall survival.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
Table 3 summarizes the outcomes of the meta-analysis. Compared with the SRPS group, the RAMPS group exhibited less intraoperative bleeding, a greater number of total retrieved lymph nodes, and a higher percentage of R0 resection (Fig. 2a–c). No significant difference was seen in other outcomes of interest. The funnel plot for retrieved lymph nodes was symmetric, indicating the absence of publication bias (Fig. 3).
Table 3Results of the meta-analysis.
Outcome of interest
No. of studies
No. of patients
OR/WMD (95% CI)
P-value
I2 (%)
Operation time (min)
3
211
−17.03 (−94.46, 60.40)
0.67
94
Blood loss (mL)
3
211
−195.2 (−223.27, −167.13)
<0.001
0
Overall morbidity
4
236
0.97 (0.54, 1.77)
0.93
0
Overall PF
4
236
0.45 (0.19, 1.10)
0.08
0
ISGPF B + C PF
2
185
0.50 (0.18, 1.38)
0.18
0
Retrieved lymph nodes
4
236
6.19 (3.72, 8.67)
<0.001
0
R0 resection
4
223
2.46 (1.13, 5.35)
0.02
0
5-year OS (%)
3
210
1.77 (0.53, 5.93)
0.35
67
WMD, weighted mean difference; OR, odds ratio; CI, confidence interval; PF, pancreatic fistula; ISGPF, International Study Group of Pancreatic Fistula; OS, overall survival.
This is the first review to assess existing evidence on clinical outcomes following RAMPS for adenocarcinoma in the body or tail of the pancreas. The results show that the perioperative mortality rate was zero, and the median 5-year OS was 37%, confirming the safety and efficacy of this procedure.
The result of meta-analysis shows that the operating time was comparable between RAMPS and SRPS, though a longer operative time was observed in some smaller series
of RAMPS group, suggesting that this may reflect the learning curve of the surgeons. As dissection during RAMPS commences from right-to-left with early division of the neck of the pancreas, it provides more superior access to control the major blood vessels including the splenic, adrenal and renal veins, blood loss was therefore reduced in RAMPS compared with SRPS.
Although no survival benefit of an extended lymphadenectomy has been shown in pancreatic adenocarcinoma resection,
thorough pathologic evaluation of lymph nodes may contribute to accurate staging. A recent review of 499 patients reported significant impact of the total number of examined lymph nodes on the estimation of stage-based survival after curative pancreatectomy for pancreatic adenocarcinoma.
Survival for node-negative (pN0) patients with <11 lymph nodes examined was worse than for pN0 patients with ≥11 lymph nodes with a 3-year survival rate of 32% vs. 50%, suggesting that metastatic nodes were missed by sampling insufficient lymph nodes. These investigators concluded that pathologic assessment of ≥11 lymph nodes in resected specimens is needed for accuracy of pancreatic adenocarcinoma staging. During SRPS, nodes at the roots of celiac or superior mesenteric artery regions are not removed. In contrast, RAMPS permits resection of these nodes in a controlled manner.
The current systematic review demonstrates that the median number of total retrieved lymph nodes after RAMPS was 21 (range, 11–30), suggesting that RAMPS fulfills the criteria of adequate node dissection.
R0 resection is an important factor determining survival in patients with pancreatic adenocarcinoma. The posterior margin is the predominant site of margin involvement of pancreatic body-tail adenocarcinoma.
The R0 resection rate of up to 88% after RAMPS in this systematic review is relatively high. In comparative studies, the cumulative R0 resection rate was 90% after RAMPS and 80% after SRPS with a pooled OR of 2.46 (95% CI 1.13–5.35). In the SRPS procedure, dissection proceeds from left-to-right, making it difficult to obtain a clear concept of where the posterior plane of dissection is, especially whenever the patient is deep-chested or obese.
On the other hand, RAMPS enables the surgeon to set up the posterior plane of dissection more easily, thus allowing for more radical resection by early identification of the renal vein and the anterior surface of the adrenal vein.
The presence of circulating tumor cells in the portal vein has been found to be associated with a higher rate of liver metastasis after pancreatic adenocarcinoma surgery.
Left-to-right mobilization and handling of the pancreato-splenic specimen without early ligation of the draining blood vessels during SRPS could increase the risk of cancer cell shedding into the portal vein. In this context, RAMPS complies with the principle of no-touch isolation. CellSearch™ method might provide the evidence for the biological benefit of this procedure.
The result of the present meta-analysis shows that RAMPS does not seem to improve survival as compared with SRPS. It is apparent that the number of patients enrolled in the current study is small with insufficient power to detect a possible difference. Mitchem et al. calculated that to compare two treatments with 5-year survival rates of 20% and 35% at the 95% CI level, a total recruitment of 556 patients was required.
The main limitation of this review is the relatively low level of evidence owing to the lack of RCT on the subject. All of the included studies were observational nature with an inherent risk of bias. There are many differences between the studies in terms of the patient selection, disease stage, surgical skill, and perioperative care. The definition of R0 resection was inhomogeneous; 12 studies simply reported that ‘surgical margins’ were negative without specified criteria,
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Another limitation is the small sample size. As adenocarcinoma of the body and tail of the pancreas is usually detected in a relatively late stage because of its delayed presentation, it is often unresectable at the time of confirmed diagnosis. In addition, as RAMPS is a novel surgical approach, surgeons are often reluctant to employ it, instead awaiting evidence of its safety and efficacy.
In conclusion, RAMPS is a safe and effective procedure for adenocarcinoma in the body or tail of the pancreas and is oncologically superior to SRPS. Although there are no data supporting a prolonged survival, more lymph nodes and an apparently greater R0 rate of resection seem evident. As all the evidence in this meta-analysis comes from observational studies involving a relatively small number of patients, larger-sample prospective RCTs comparing RAMPS with SRPS are required to obtain a more convincing conclusion.
Conflicts of interest
The authors declare that they have no potential competing interests. The authors received no funding for this work.
Radical antegrade modular pancreatosplenectomy procedure for adenocarcinoma of the body and tail of the pancreas: ability to obtain negative tangential margins.
A modification of radical antegrade modular pancreatosplenectomy for adenocarcinoma of the left pancreas: significance of en bloc resection including the anterior renal fascia.
Superior mesenteric artery-first approach in radical antegrade modular pancreatosplenectomy for borderline resectable pancreatic cancer: a technique to obtain negative tangential margins.
Comparison of surgical outcomes between radical antegrade modular pancreatosplenectomy (RAMPS) and standard retrograde pancreatosplenectomy (SPRS) for left-sided pancreatic cancer.
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