有馬 豪

BACKGROUND: Preservation of plantar subcutaneous fat is crucial for cushioning in the surgical treatment of acral melanoma of the sole. However, no studies exist on the relationship between deep margins and prognosis. We aimed to retrospectively compare the prognoses of different deep margins (within or beyond the subcutaneous fat) in patients with invasive acral melanoma of the sole who underwent wide local excision. METHODS: In this multi-institutional retrospective study, survival was compared between 2 groups of patients: those with tumors excised within (S group) and those beyond the subcutaneous fat (D group). RESULTS: In total, 464 patients were included. Cox multivariable analyses showed that the depth of the deep excision margin was not associated with local recurrence-free survival, overall survival, or distant metastasis-free survival (hazard ratios of 1.20, P = .36; 1.10, P = .66; and 1.42, P = .05, respectively). However, excision beyond the subcutaneous fat was negatively associated with disease-free survival (hazard ratio 1.45, P = .02). After propensity score matching (both groups, n = 139), no significant differences were observed in survival outcomes between the S and D groups (5-year local recurrence-free survival: 72.8 vs 66.8%, P = .55; 5-year disease-free survival: 55.3 vs 43.7%, P = .24; 5-year overall survival: 76.2 vs 73.2%, P = .52; 5-year distant metastasis-free survival: 63.3 vs 54.1%, P = .13). Subgroup analysis of American Joint Committee on Cancer stages revealed no significant differences in survival outcomes between the 2 groups at any stage. CONCLUSION: Wide local excision beyond the subcutaneous fat was not associated with survival benefit of acral melanoma of the sole. Excision within the subcutaneous fat may represent the optimal deep margin.

The skin, the body's largest organ, covers the entire body and consists of three layers: the epidermis, dermis, and subcutaneous tissue. Its structure and properties vary by body region. Although homeobox (HOX) genes are implicated in mechanisms contributing to regional skin property differences, their influence is not completely understood. In this study, we focused on the relationships between HOX gene expression to regional differences in dermal structure and skin elasticity. Our results revealed significantly higher HOXA cluster expression in skin tissues and cells derived from the body in comparison to those derived from the face. Among HOXA genes highly expressed in the body, HOXA9 was found to regulate dermal fibroblast proliferation and extracellular matrix (ECM)-related gene expression, both associated with skin elasticity. Furthermore, HOXA9 was shown to affect cell proliferation and ECM-related gene expression through IGF-1 signaling. Collectively, our findings suggest that HOXA genes are expressed differently in different body regions, variably affecting dermal structure and cellular functions, thus contributing to regional variation in skin.

PURPOSE: Adjuvant anti-PD-1 (adj PD-1) antibodies are extensively used to improve survival in patients with resected melanoma. Clinical trials on adj PD-1 antibodies have revealed significant improvements in recurrence-free survival (RFS); however, few of these trials have included patients with acral melanoma (AM). METHODS: Clinical data were retrospectively collected from Japanese patients who underwent resection of stage III sole AM between 2014 and 2021. Survival outcomes, including RFS, distant metastasis-free survival (DMFS), and overall survival (OS), were compared between patients without adjuvant therapy (OBS group) and those receiving adj PD-1 group. RESULTS: This study included 139 patients (OBS: 79; adj PD-1: 60), with a median follow-up of 2.6 years. The baseline characteristics were comparable, except for age and nodal metastasis. No significant differences in survival were observed between the OBS and adj PD-1 groups (3-year RFS: 36.7% v 27.5%, P = .13; 3-year DMFS: 51.0% v 45.3%, P = .51; 3-year OS: 65.3% v 67.4%, P = .45). Multivariate analysis showed no survival benefit of adj PD-1 (RFS: hazard ratio [HR], 1.25, P = .29; DMFS: HR, 1.03, P = .89; and OS: HR, 0.69, P = .23). Each survival outcome after propensity score matching confirmed no significant difference between the matched OBS group (n = 52) and adj PD-1 group (n = 52; 3-year RFS: 34.3% v 25.9%, P = .22; 3-year DMFS: 45.6% v 46.5%, P = .85; 3-year OS: 60.7% v 68.9%, P = .29). CONCLUSION: Adj PD-1 did not improve the prognosis in sole AM. However, further studies are essential to evaluate the efficacy of the adj anti-PD-1 antibody in AM.