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Background: In recent years there has been a plea to abandon the pelvic lymph node dissection in the treatment of patients with metastatic melanoma to the groin. A trend towards a conservative surgical treatment is already evolving in several European countries. The purpose of this study is to identify factors associated with pelvic nodal involvement, in order to improve selection of patients whom might benefit from a pelvic nodal dissection.Methods: A retrospective analysis was performed on prospectively collected data concerning patients who underwent an inguinal lymph node dissection (ILND) with pelvic lymph node dissection for metastatic melanoma at the University Medical Center Groningen. Multivariable logistic regression analysis was performed to determine factors associated with pelvic nodal involvement. Diagnostic accuracy was calculated for F-18-FDG PET + contrast enhanced CT-scan and F-18-FDG PET + low dose CT-scan.Results: Two-hundred-and-twenty-six ILND's were performed in 223 patients. The most common histologic subtype was superficial spreading melanoma (42.6%). In patients with micrometastatic disease, 15.7% had pelvic nodal involvement vs 28.2% in patients with macrometastatic disease (p: 0.030). None of the characteristics known prior to the ILND, were associated with pelvic nodal involvement. Imaging methods were unable to accurately predict pelvic nodal involvement. Negative predictive value was 78% for F-18-FDG PET + low dose CT-scan and 86% for an F-18-FDG PET + contrast enhanced CT-scan.Conclusion: There are no patient- or tumor characteristics available that can predict pelvic nodal involvement in patients with melanoma metastasis to the groin. As no imaging technique is able to predict pelvic nodal involvement it seems unjust to abandon the pelvic lymph node dissection. (C) 2018 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

SummaryThe mechanisms by which melanoma and other cancer cells evade anti-tumor immunity remain incompletely understood. Here, we show that the growth of tumors formed by mutant BrafV600E mouse melanoma cells in an immunocompetent host requires their production of prostaglandin E2, which suppresses immunity and fuels tumor-promoting inflammation. Genetic ablation of cyclooxygenases (COX) or prostaglandin E synthases in BrafV600E mouse melanoma cells, as well as in NrasG12D melanoma or in breast or colorectal cancer cells, renders them susceptible to immune control and provokes a shift in the tumor inflammatory profile toward classic anti-cancer immune pathways. This mouse COX-dependent inflammatory signature is remarkably conserved in human cutaneous melanoma biopsies, arguing for COX activity as a driver of immune suppression across species. Pre-clinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors, implying that COX inhibitors could be useful adjuvants for immune-based therapies in cancer patients.

Melanocytes respond to UVR not only by producing melanin, but also by proliferating. This is essentially a protective response. We have studied the melanocyte proliferative response after a single UVR exposure to neonatal mice. At 3 days post-UVR in wild-type neonates we observed a marked melanocyte activation not seen in adults. Melanocytes migrated to the epidermal basal layer, their numbers peaking at 3-5 days after UVR then diminishing. They appeared to emanate from the hair follicle, migrating to the epidermis via the outer root sheath. In melanoma-prone mice with melanocyte-specific overexpression of Hras(G12V), basal layer melanocytes were increased in size and dendricity compared to UVR-treated wild-type mice. Melanocytes in mice carrying a pRb pathway cell-cycle defect (oncogenic Cdk4(R24C)) did not show an enhanced response to UVR such as those carrying Hras(G12V). The exquisite sensitivity to UVR-induced proliferation and migration that characterizes neonatal mouse melanocytes may partly explain the utility of this form of exposure for inducing melanoma in mice that carry oncogenic mutations.

Aim: In this study, the short-term and tong-term morbidity was assesed after axillary sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (SLNB/ALND) in patients with cutaneous melanoma.Methods: Between 1995 and 2003, 119 axillary SLNBs were performed for cutaneous melanoma. Fifty-eight patients met the inclusion criteria and entered the study.Results: Forty-four patients underwent SLNB alone and 14 patients underwent axillary lymph node dissection after positive SLNB. Complications after SLNB atone: post-operative bleeding (n = 2), seroma (n = 1) and slight lymphedema 11%. Complications after SLNB/ALND: wound infections (n = 2), seroma (n = 5) and slight lymphedema 7%. There were differences between the two groups in short-term complications (p Conclusion: Axillary SLNB atone had a tow complication rate. However, SLNB followed by completion ALND was associated with an increased risk of short- and long-term complications. (c) 2005 Elsevier Ltd. All rights reserved.