Refinements in dorsoulnar flap of the thumb: 15 cases.

PURPOSE: We report 2 modifications of the classic Brunelli flap to avoid vascular compromise and first web contracture, common when using medium or large flaps. METHODS: We treated 15 patients with posttraumatic loss of palmar surface and distal amputation of the thumb, with dorsoulnar flap associated with 2 refinements. The first technical tip was an adipofascial extension proximal in the flap aimed to decrease the morbidity of the donor site without changing the potential covering of the flap. The second was always to graft the pedicle of the flap, avoid vascular compression problems, and moreover, to use the pedicle to cover the traumatic area. All ulnar dorsal digital nerves of the flaps were reconnected to one of the volar digital nerves. The minimum patient follow-up was 12 months. RESULTS: All flaps achieved primary healing without major complications. There were no donor site problems. Cosmetic debulking of the flap over the pedicle has not been required. CONCLUSIONS: The Brunelli flap is a good technique to cover small and moderate defects of the thumb, although the drawback of this procedure is the lack of sensory recovery. The refinements of this series can help to improve the use of this flap and avoid complications in the donor site.

Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures.

Targeted treatment of advanced melanoma could benefit from the precise molecular characterization of melanoma samples. Using a melanoma-specific selection of 217 genes, we performed targeted deep sequencing of a series of biopsies, from advanced melanoma cases, with a Breslow index of ≥ 4 mm, and/or with a loco-regional infiltration in lymph nodes or presenting distant metastasis, as well of a collection of human cell lines. This approach detected 3-4 mutations per case, constituting unique mutational signatures associated with specific inhibitor sensitivity. Functionally, case-specific combinations of inhibitors that simultaneously targeted MAPK-dependent and MAPK-independent mechanisms were most effective at inhibiting melanoma growth, against each specific mutational background. These observations were challenged by characterizing a freshly resected biopsy from a metastatic lesion located in the skin and soft tissue and by testing its associated therapy ex vivo and in vivo using melanocytes and patient-derived xenografted mice, respectively. The results show that upon mutational characterization of advanced melanoma patients, specific mutational profiles can be used for selecting drugs that simultaneously target several deregulated genes/pathways involved in tumor generation or progression.