Ex-Vivo Intra-Arterial Methylene Blue Dye Injection Augments Pathology Lymph-Nodes Harvest Following Colorectal Cancer Surgery
Pierpaolo Sileri1, Luana Franceschilli*1, Marco D'Eletto1, Giulio P. Angelucci1, Sara Lazzaro1, Mara Capperucci1, Giampiero Palmieri2, Nicola Di Lorenzo1, Vincenzo Formica3, Achille Gaspari1
1Surgery, University of Rome Tor Vergata, Rome, Italy; 2Pathology, University of Rome Tor Vergata, rome, Italy; 3Oncology, University of Rome Tor Vergata, rome, Italy
Introduction: Lymph node (LN) assessment has a critical role in staging colorectal cancer (CRC) thus influencing 5-year survival rates. However, several studies have shown that nodal harvest is highly variable andoften inadequate. In this prospective study we evaluated if ex-vivo intra-arterial methylene blue dye injection results in a better and more accurate lymph-nodes harvest and staging. We also compared these results with data prospectively collected from a cohort of patient who underwent CRC surgery prior the beginning of this study.Patients and Methods: Between August 2009 and September 2010, a total of 105 consecutive patients with primary resectable CRC were enrolled for this study. Patients with previous colorectal surgery, evidence of advanced or metastatic disease at surgery, were excluded. Same surgeons and same pathologists were involved in the study. After surgery, retrieved specimens were ex-vivo injected (56) or not (49) with methylene blue dye and sent for standard pathology. The two groups were well-matched for age, gender, BMI, neoadjuvant therapy and type of surgery. Lymph-nodes were grouped into four categories according to the size: <1mm, 1-2mm, 2-4mm and greater than 4mm. These results were also compared to data obtained from a cohort of 146 patients who underwent CRS surgery between September 2005 and July 2009. Mann-Whitney and Student t-test were used for statistical analysis. Results: Methylene blue injection failed in 3 cases (5.7%) mainly due to extravasation of colorant, mis-identification of the artery and incomplete mapping. The average lymph-node harvest was 17+/-6 (range 10-33) in the stained and 15+/-7 (range 4-34) in the unstained group. Methylene blue injection reduced the risk of inadequate LNs harvest (LNs<8: 14% to 0,p=0.05; LNs<12: 32% to 21%, p=018). The largest difference was found in size groups between <1 and 4mm causing a shift in size distribution toward smaller lymph-nodes retrieval. This difference was significantly more evident for LN <1mm (9% vs. 5%, p=0.007). When we compare these results to data obtained before the beginning of this study, we confirmed a significant reduction of inadequate harvesting when methylene blue dye is used (LN<8; from 19% vs. 0%; p=0.002) (LN<12; from 40% vs. 21%,p=0.004). The failed injection did not significantly influence the mean number of retrieved LNs.Conclusions: Ex-vivo intra-arterial methylene blue dye injection augments lymph-nodes retrieval thus allowing a more accurate colorectal cancer staging and possibly the oncologic outcome.
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