A meta-analysis of extended versus standard lymphadenectomy in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma

Abstract

Background: Lymph node involvement in pancreatic adenocarcinoma is a key prognostic factor. Therefore, extending the number of lymph node stations excised in pancreatoduodenectomy may be beneficial to patients with pancreatic adenocarcinoma. This systematic review and meta-analysis examines the outcomes of extended versus standard lymphadenectomy in the published literature.

Methods: A meta-analysis of randomized controlled trials (RCTs) comparing extended with standard lymphadenectomy in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma was performed. Perioperative outcomes were assessed as pooled odds ratios (ORs) and weighted mean differences. Overall survival was analysed for patients with positive and negative lymph nodes. Results were reported according to the PRISMA statement.

Results: Five RCTs were included, accounting for 724 patients. Extended lymphadenectomy was associated with greater operative time [mean difference: 63 min, 95% confidence interval (CI) 29-96; P < 0.001], increased need for blood transfusions (mean difference: 0.20, 95% CI 0.01-0.30; P = 0.030) and greater postoperative morbidity (OR 1.5, 95% CI 1.25-2.00; P = 0.030), as well as with prolonged diarrhoea after circumferential autonomic nerve dissection around major vessels (OR 12.2, 95% CI 5.3-28.5; P < 0.001). Median survival was similar across the groups in the whole cohort, as well as in subgroups of patients with, respectively, positive and negative lymph nodes.

Conclusions: Extended lymphadenectomy has a harmful impact on patients undergoing oncological pancreatoduodenectomy compared with standard lymphadenectomy.

Figure 1

Results of the PRISMA-based protocol for the study inclusion and exclusion process

Figure 2

Lymph nodes harvested during (a) standard and (b) extended lymphadenectomy. The colour code indicates numbers of studies harvesting the relevant lymph node groups (Japanese classification). (c) Forest plot illustrating the number of resected lymph nodes (random-effects model). The vertical line shows the null hypothesis; the surface areas of the blue rectangles indicate the weight of individual studies in the pooled analysis and the black diamond depicts the pooled effect size. 95% CI, 95% confidence interval. (Adapted from the Japanese Gastric Cancer Association, with permission)

Figure 3

Summary survival curves with 95% confidence bands (dashed lines) represented by study groups (black lines for extended lymphadenectomy and grey lines for standard lymphadenectomy) for (a) the overall population, (b) lymph node-positive patients, and (c) lymph node-negative patients

Figure 4

Pooled estimates of hazard ratios (HRs) for each interval of time (black squares) and for the overall follow-up (grey horizontal line) in (a) lymph node-positive and (b) lymph node-negative patients. Vertical black lines represent 95% confidence intervals around the pooled HRs in each interval of time and the grey dashed horizontal line represents the 95% interval around the HR pooled over the entire follow-up. Circles represent estimated HRs extracted from studies