Prognostic significance of drainage to pelvic nodes at sentinel lymph node mapping in patients with extremity melanoma
ABSTRACT Patients undergoing sentinel lymph node (SLN) mapping for lower extremity melanoma may have drainage to pelvic nodes (DPN) in addition to superficial inguinal nodes. These nodes are not sampled routinely at SLN biopsy. Factors predicting DPN and its prognostic significance were assessed in a large cohort of patients undergoing an SLN biopsy. Three hundred and twenty five patients with single primary melanomas of the lower extremity or buttocks who underwent SLN mapping were identified from our prospective melanoma database (December 1995-October 2008). Associations of clinical and pathologic factors with DPN and time to melanoma recurrence (TTR) were analyzed by logistic and Cox regression, respectively. DPN was common, occurring in 23% of cases. Increased Breslow's thickness (P=0.007) and age (P=0.01) were associated with DPN by multivariate analysis. Patients with DPN were not more likely to have a positive SLN; however, SLN- patients with DPN showed a shorter TTR (P=0.02) in a multivariable model including thickness and ulceration. With age included in the model, DPN remained marginally associated with TTR in this group (P=0.08). The pelvic recurrence rates observed were similar in recurrent patients with DPN compared with those without DPN (39% in both groups). In conclusion, DPN occurs in almost one-quarter of patients with lower extremity melanoma and is marginally associated with a shorter TTR in SLN- patients.
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ABSTRACT: Sentinel lymph node (SLN) mapping is a critical procedure for SLN biopsy and its diagnosis as tumor metastasis in clinical practice. However, SLN mapping agents used in the clinic frequently cause side effects and complications in the patients. Here, we report the development of a near-infrared (NIR) emitting polymeric nanogel with hydrodynamic diameter of ~28 nm - which is the optimal size for SLN uptake - for noninvasive fluorescence mapping of SLN in a mouse. This polymeric nanogel was obtained by coupling Cy7, an NIR dye, to the self-assembled nanogel from disulfide-linked dextran-deoxycholic acid conjugate with the dextran of 10 kDa, denoted as Dex-Cy7. Fluorescence imaging analysis showed that Dex-Cy7 nanogels had an enhanced photostability when compared to Cy7 alone. After intradermal injection of Dex-Cy7 nanogel into the front paw of a mouse, the nanogels were able to migrate into the mouse's axillary lymph node, exhibiting longer retention time and higher fluorescence intensity in the node when compared to Cy7 alone. An immunohistofluorescence assay revealed that the nanogels were localized in the central region of lymph node and that the uptake was largely by the macrophages. In vitro and in vivo toxicity results indicated that the dextran-based nanogels were of low cytotoxicity at a polymer concentration up to 1,000 μg/mL and harmless to normal liver and kidney organs in mice at an intravenous dose of 1.25 mg/kg. The results of this study suggest that NIR-emitting polymeric nanogels based on bioreducible dextran-deoxycholic acid conjugates show high potential as fluorescence nanoprobes for safe and noninvasive SLN mapping.International Journal of Nanomedicine 12/2014; 9:5667-5682. DOI:10.2147/IJN.S70593 · 4.20 Impact Factor
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ABSTRACT: Patients with cutaneous melanoma (CM) on the trunk have a worse prognosis than those with extremity CM. One reason could be multiple or uncommon (outside axilla or groin) sentinel node locations (SNLs). We identified 859 patients who underwent sentinel node biopsy for trunk (n = 465) or extremity (n = 394) CM in three Swedish healthcare regions from 2000 to 2008. We collected patient, tumor, and sentinel node characteristics through clinical registers and medical records. We investigated the distribution of SNLs in a logistic regression model, and risk of overall and melanoma-specific death through 2011 in a multivariable Cox regression model. Trunk CM was associated with multiple SNLs (31 vs. 7 %; odds ratio [OR] 7.1; 95 % confidence interval [CI] 4.6-11.5; p < 0.001) but not uncommon SNLs (8 vs. 7 %; OR 1.1; 95 % CI 0.6-1.9; p = 0.75) compared with extremity CM. The increased risk of melanoma-specific death was confirmed for trunk CM (hazard ratio [HR] 1.9; 95 % CI 1.3-2.9; p = 0.003), especially on the upper back (HR 2.3; 95 % CI 1.4-3.6; p < 0.001) compared with extremity CM. Uncommon SNLs (HR 0.5; 95 % CI 0.2-1.4; p = 0.21) or multiple SNLs (HR 1.1; 95 % CI 0.4-2.9; p = 0.81) were not associated with melanoma-specific death compared with those with common/single SNL. Trunk melanomas were associated with multiple lymph drainage, but the worse prognosis of trunk melanomas could not be explained by the increased frequency of multiple or uncommon SNLs.Annals of Surgical Oncology 05/2014; 21(11). DOI:10.1245/s10434-014-3744-0 · 3.94 Impact Factor