Updated Systematic Review and Meta-Analysis: Lymphatic mapping in colon cancer depending on injection time and tracing agent

Objectives Lymphatic spreading is a main driver of metastasis and, thus, associated death in colon cancer. Although resection within established resection lines provides a good lymph node yield, aberrant lymphatic drainage pathways may be missed. Lymphatic mapping can compensate for this shortcoming. Currently, different protocols exist for lymphatic mapping procedures. This meta-analysis assessed which protocol has the best capacity to detect tumour-draining and possibly metastatic lymph nodes.

Methods A systematic review was conducted according to PRISMA guidelines, including Medline, Web of Science, Embase and Cochrane. A second search using the same search strategies was conducted on February 13th, 2023. Eligible were prospective trials with in vivo tracer application. The risk of bias was evaluated using the QUADAS–2 tool. Traced lymph node rates and aberrant drainage detection rate were analyzed.

Results 58 studies met the inclusion criteria, of which 42 searched for aberrant drainage.While a preoperative tracer injection significantly increased the traced lymph node rates compared to intraoperative tracing (30.1% (15.4, 47.3) vs. 14.1% (11.9, 16.5), p=0.03), no effect was shown for the tracer used (p=0.740) or the application sites comparing submucosal and subserosal injection (22.9% (14.1, 33.1) vs. 14.3% (12.1, 16.8), p=0.07). Preoperative tracer injection resulted in a significantly higher rate of detected aberrant lymph nodes compared to intraoperative injection (26.3% [95% CI 11.5, 44.0] vs. 2.5% [95% CI 0.8, 4.7], p<0.001). Analyzing 112 individual patient data sets from eight studies revealed a significant impact on aberrant drainage detection for injection timing, favoring preoperative over intraoperative injection (OR 0.050 [95%CI 0.010-0.176], p<0.001) while Indocyanine green presented itself as the superior tracer (OR 0.127 [95%CI 0.018-0.528], p=0.012).

Conclusion This meta-analysis demonstrates that a preoperative tracer application and earlier tumour stages allow a higher mapped lymph node yield. In contrast, tracer or application sites have no relevant impact on this ratio. However, for the detection of aberrant lymph nodes, preoperative tracer application, usage of ICG, and a submucosal application demonstrated significantly better results.Optimized lymphatic mapping techniques result in significantly higher detection of aberrant lymphatic drainage patterns and thus enable a personalized approach to reducing local recurrence ([Abb. 1]).

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Publication History

Article published online:
28 August 2023