The role of FDG-PET-CT is limited in initial staging of nodal metastasis for thin cutaneous melanoma.

INTRODUCTION: Positron emission tomography computed tomography (PET-CT) is often used to stage nodal metastases in thin cutaneous melanoma, with limited evidence. METHODS: A retrospective review of patients with cutaneous malignant melanoma treated at our institution was performed from 2005 to 2015, identifying those who received a PET-CT prior to lymphadenectomy. Biopsy features, lymph node status, and PET-CT results were collected. We calculated the overall sensitivity, specificity, accuracy, likelihood ratios, and positive predictive value of PET-CT in identifying nodal metastases. Results were stratified by initial biopsy tumor depth. RESULTS: We identified 367 cases; 95 obtained a PET-CT prior to lymphadenectomy. Overall, sensitivity and specificity of PET-CT was 34.6% and 95.4%, respectively. The positive likelihood ratio and negative likelihood ratio were 7.62 and 0.68, respectively. The accuracy was 78.2%. The positive predictive value for T3 and T4 melanomas were 100% and 81.4%, respectively. For thin melanomas, specificity and accuracy was 88.2% and 88.2%, respectively. CONCLUSIONS: PET-CT has low specificity and its use alone is not recommended for initial staging of nodal metastases in thin cutaneous malignant melanoma.

Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes?

BACKGROUND: Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in the media and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications. STUDY DESIGN: Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) for stage 0-III PAMs vs non-PAMs. Kaplan-Meier survival curves were then plotted for OS and MSS and compared using the log-rank test. RESULTS: The clinical presentation of melanoma was similar for PAM and non-PAM patients. There was no significant difference in recurrence between the 2 groups; for PAM patients, 38.5% of patients had recurrence, as compared with 36.6% of non-PAM patients (p = 0.641). For PAM patients, median follow-up was 14.6 years (range 0 to 42.6 years) and 11.1 years (0 to 48.5 years) for the non-PAM patients. No significant differences in DFS, MSS, or OS were identified on univariable or multivariable analysis for PAM vs non-PAM patients in stage 0/I/II and stage III cutaneous melanoma, respectively (p = 0.880 DFS, p = 0.219 OS, and p = 0.670 MSS). CONCLUSIONS: We observed no difference in DFS, OS, or MSS between the 2 groups. Pregnant patients should be screened for melanoma in a similar manner to nonpregnant patients and should be counseled that their survival is not adversely affected by their pregnancy.

Insights into Local Tumor Microenvironment Immune Factors Associated with Regression of Cutaneous Melanoma Metastases by Mycobacterium bovis Bacille Calmette-Guérin.

Mycobacterium bovis bacille Calmette-Guérin (BCG) is listed as an intralesional (IL) therapeutic option for inoperable stage III in-transit melanoma in the National Comprehensive Cancer Network Guidelines. Although the mechanism is unknown, others have reported up to 50% regression of injected lesions, and 17% regression of uninjected lesions in immunocompetent patients after direct injection of BCG into metastatic melanoma lesions in the skin. BCG and other mycobacteria express ligands capable of stimulating the γ9δ2 T cells. Therefore, we hypothesized that γ9δ2 T cells play a role in promoting BCG-mediated antitumor immunity in patients treated with IL-BCG for in-transit cutaneous melanoma metastases. Indeed, we found γ9δ2 T cell infiltration in melanoma skin lesions during the course of IL-BCG treatment. Gene expression analysis revealed that BCG injection elicits the expression of a vast array of chemokines in tumor lesions, including strong expression of CXCL9, 10, and 11, a set of chemokines that attract T cells expressing the CXCR3 chemokine receptor. In corroboration with our hypothesis, approximately 85% of γδ T cells express high levels of CXCR3 on their surface. Importantly, the injected tumor lesions also express genes whose protein products are the antigenic ligands for γδ T cells (BTN3A1 and MICB), and the cytokines that are the typical products of activated γδ T cells. Interestingly, we also found that γδ T cells infiltrate the regressed lesions that did not receive BCG injections. Our study suggests that γ9δ2 T cells may contribute to melanoma regression induced by IL-BCG treatment.

The Impact of Smoking on Sentinel Node Metastasis of Primary Cutaneous Melanoma.

BACKGROUND: Although a well-established causative relationship exists between smoking and several epithelial cancers, the association of smoking with metastatic progression in melanoma is not well studied. We hypothesized that smokers would be at increased risk for melanoma metastasis as assessed by sentinel lymph node (SLN) biopsy. METHODS: Data from the first international Multicenter Selective Lymphadenectomy Trial (MSLT-I) and the screening-phase of the second trial (MSLT-II) were analyzed to determine the association of smoking with clinicopathologic variables and SLN metastasis. RESULTS: Current smoking was strongly associated with SLN metastasis (p = 0.004), even after adjusting for other predictors of metastasis. Among 4231 patients (1025 in MSLT-I and 3206 in MSLT-II), current or former smoking was also independently associated with ulceration (p < 0.001 and p < 0.001, respectively). Compared with current smoking, never smoking was independently associated with decreased Breslow thickness in multivariate analysis (p = 0.002) and with a 0.25 mm predicted decrease in thickness. CONCLUSION: The direct correlation between current smoking and SLN metastasis of primary cutaneous melanoma was independent of its correlation with tumor thickness and ulceration. Smoking cessation should be strongly encouraged among patients with or at risk for melanoma.

Second Primary Melanoma: Risk Factors, Histopathologic Features, Survival, and Implications for Follow-Up.

The impact on survival of a second primary melanoma (SPM) is unclear. We used our melanoma center's database to examine clinicopathologic risk factors and outcomes of stage 0 to IV cutaneous melanoma in patients with one versus two primaries. Among 12,325 patients with primary melanoma, 969 (7.86%) developed SPM. SPMs were significantly thinner than autologous primary melanomas (P = 0.01), and 451 SPM patients had better overall and melanoma-specific survival than 451 prognostically matched non-SPM patients (P < 0.0001 and 0.0001, respectively) at a median follow-up of 142.37 months. Patients with cutaneous melanoma are at high risk for development of SPM, but the development of SPM does not seem to impair survival.

Targeted amino acid supplementation in diabetic foot wounds: pilot data and a review of the literature.

BACKGROUND: Diabetic foot wounds are a highly morbid and costly complication of diabetes mellitus. Targeted amino acid supplementation, by increasing tissue hydroxyproline concentrations, has been implicated in improved wound outcomes in surgical incisions and chronic wounds, and after radiation injury. A major component of collagen, hydroxyproline is a surrogate marker used commonly for tissue collagen concentrations. This paper reviews the literature pertaining to amino acid supplementation and wound healing, and also evaluates our pilot data relating to supplementation with arginine, glutamine, and beta-hydroxy-beta-methylbutyrate (HMB) in the treatment of diabetic foot ulcers. METHODS: For the pilot study, nine patients scheduled to undergo wound debridement for diabetic foot ulcers were randomized prospectively to be a part of either a placebo group or a treatment group that received supplementation twice daily for 2 wks. Tissue samples were collected both before and after 2 wk of supplementation. The results of assay of the samples for hydroyproline were then analyzed via a one tailed Student t-test to evaluate tissue concentrations of hydroxyproline. For the literature review in the study, the MEDLINE/PubMed database was reviewed, using search terms contained in the Medical Subject Headings (MeSH). RESULTS: The treatment group in the study exhibited a significantly greater hydroxyproline concentration after supplementation than before it (p=0.03). The mean percent change in the tissue hydroxyproline concentration for arginine, glutamine, and HMB group was +67.8%, with a standard deviation (SD) of 129.89. The mean percent change for the corresponding amino acids in the placebo group was -78.4%, with an SD of 20.55. The review of the MEDLINE/PubMed literature revealed only two human studies of amino acid supplementation in patients with diabetic foot wounds, one of which found a significant improvement in wound-depth and wound-appearance scores. CONCLUSIONS: Given the results of our pilot study, and on the basis of a review of the literature, the administration of a simple amino acid supplement may improve the healing of diabetic foot wounds via increased collagen production.