Four Immune Modulating Genes in Primary Melanoma That Predict Metastatic Potential.

INTRODUCTION: Histologic characteristics cannot adequately predict which patients are at risk of developing metastatic disease after excision of primary cutaneous melanoma. The aim of this study was to identify immunomodulatory genes in primary tumors associated with development of distant metastases. MATERIALS AND METHODS: Thirty-seven patients with primary melanoma underwent surgical excision. RNA was extracted from the primary tumor specimens. cDNA was synthesized and used with Human Gene Expression microarray. Differential expression of 74 immunomodulatory genes was compared between patients who developed distant metastases and those who did not. RESULTS: Six of 37 patients developed distant metastases during the time of the study. Differential expression of microarray data showed upregulation of four immunomodulatory genes in this group. These four genes-c-CBL, CD276, CXCL1, and CXCL2-were all significantly overexpressed in the metastatic group with differential expression fold change of 1.15 (P = 0.01), 1.16 (P = 0.04), 2.51 (P < 0.001), and 1.68 (P < 0.02), respectively. CXCL1 had particularly high predictive value with an area under the curve of 0.80. Multivariate analysis showed only expression of CXCL1 (P = 0.01) remains predictive of distant metastases in melanoma patients. This result was confirmed using quantitative real-time polymerase chain reaction. CONCLUSIONS: CXCL1, CXCL2, c-CBL, and CD276 are immunomodulatory genes present in primary melanoma that are strongly associated with development of metastatic disease. Identification of their presence, particularly CXCL1, in the primary tumor could be used as a predictor of future risk of metastatic disease and thereby to identify patients who might benefit early from immunotherapy.

Subclavian Vein Stenosis Imitating Inflammatory Breast Cancer.

Unilateral breast erythema, edema, and peau d'orange are classically associated with inflammatory breast cancer. However, occasionally this constellation of symptoms is seen with other causes. Maintaining a broad differential can therefore save a prospective patient from months of worry about a possible cancer diagnosis, untreated symptoms, and unnecessary and expensive tests. Here we present the case of a 75-year-old woman with a history of pacemaker placement complicated by left upper extremity deep venous thrombosis (DVT) who subsequently developed left breast peau d'orange, swelling, and erythema. After initially being worked up for inflammatory breast cancer, including multiple breast biopsies, she was then referred to specialists in cardiology, allergy, pulmonology, rheumatology, dermatology, lymphedema therapy, and vascular surgery undergoing an exhaustive workup that spanned nearly a year. Eventually, a venogram was performed, which revealed complete occlusion of her left subclavian vein. After undergoing angioplasty and stenting, her symptoms resolved.

Utility of delayed surgical repair of neonatal brachial plexus palsy.

OBJECT: Neonatal brachial plexus palsy (NBPP) represents a significant health problem with potentially devastating consequences. The most common form of NBPP involves the upper trunk roots. Currently, primary surgical repair is performed if clinical improvement is lacking. There has been increasing interest in "early" surgical repair of NBPPs, occurring within 3-6 months of life. However, early treatment recommendations ignore spontaneous recovery in cases of Erb's palsy. This study was undertaken to evaluate the optimal timing of surgical repair in this group with respect to quality of life. METHODS: The authors formulated a decision analytical model to compare 4 treatment strategies (no repair or repair at 3, 6, or 12 months of life) for infants with persistent NBPPs. The model derives data from a critical review of published studies and projects health-related quality of life and quality-adjusted life years over a lifetime. RESULTS: When evaluating the quality of life of infants with NBPP, improved outcomes are seen with delayed surgical repair at 12 months, compared with no repair or repair at early and intermediate time points, at 3 and 6 months, respectively. ANOVA showed that the differences among the 4 groups are highly significant (F = 8369; p < 0.0001). Pairwise post hoc comparisons revealed that there are highly significant differences between each pair of strategies (p < 0.0001). Meta-regression showed no evidence of improved outcomes with more recent treatment dates, compared with older ones, for either nonsurgical or for surgical treatment (p = 0.767 and p = 0.865, respectively). CONCLUSIONS: These data support a delayed approach of primary surgical reconstruction to optimize quality of life. Early surgery for NBPPs may be an overly aggressive strategy for infants who would otherwise demonstrate spontaneous recovery of function by 12 months. A randomized, controlled trial would be necessary to fully elucidate the natural history of NBPP and determine the optimal time point for surgical intervention.