Long-term survival and immunological parameters in metastatic melanoma patients who responded to ipilimumab 10 mg/kg within an expanded access programme.

Background: Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.

A single centre melanoma thickness trend (1985-2009) in relation to skin areas accessible and non-accessible to self-inspection.

Background/objectives: Melanoma has become a major public health problem worldwide and its incidence in individuals of Caucasian origin continues to rise. The objective was to determine historical changes in thickness, melanoma proportions and anatomical site of presentation over a 25-year period in our Department.

Methods: This was a historical retrospective study (January 1985 to December 2009).

Ipilimumab experience in heavily pretreated patients with melanoma in an expanded access program at the University Hospital of Siena (Italy).

Aim Of Study: To evaluate the feasibility of ipilimumab treatment for metastatic melanoma outside the boundaries of clinical trials, in a setting similar to that of daily practice.

Methods: Ipilimumab was available upon physician request in the Expanded Access Programme for patients with life-threatening, unresectable stage III/IV melanoma who failed or did not tolerate previous treatments and for whom no therapeutic option was available. Induction treatment with ipilimumab 10 mg/kg was administered intravenously every 3 weeks, for a total of 4 doses, with maintenance doses every 12 weeks based on physicians' discretion and clinical judgment.

The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications.

The promising new class of immunomodulating antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) has been extensively tested in clinical trials and found to be active against cutaneous melanoma and other tumor histotypes. Inhibition of CTLA-4 characteristically induces well-identified side effects for which the definition "immune-related adverse events" (irAEs) has been proposed. IrAEs mainly include colitis/diarrhea, dermatitis, hepatitis, and endocrinopathies; uveitis, nephritis, and inflammatory myopathy also have been reported occasionally.

Objective follow-up of atypical melanocytic skin lesions: a retrospective study.

Various authors have suggested that information from longitudinal observation (follow-up) of dynamic changes in atypical melanocytic pigmented skin lesions (MPSL) could enable identification of early malignant melanoma escaping initial observation due to an absence of specific clinical and dermoscopic features. The aim of our retrospective study was to determine the existence of numerical variables regarding changes in MPSL that could be useful to differentiate early melanomas and atypical nevi. The study was carried out in two Italian dermatology Centres.

S100A13 is a new angiogenic marker in human melanoma.

Angiogenesis is critical in melanoma progression and metastasis and relies on the synthesis and release of proangiogenic molecules such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factors (FGFs). S100A13 is a small calcium-binding protein that facilitates the release of FGF-1, the prototype of the FGF family. S100A13 is upregulated in astrocytic gliomas, in which it correlates with VEGF-A expression, microvessel density and tumor grading, and promotes a more aggressive, invasive phenotype in lung cancer-derived cell lines.

Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions.

Beclin 1 and LC3 autophagic genes are altered in several human cancer types. This study was designed to assess the expression of Beclin 1 and LC3 in cutaneous melanocytic lesions, in which they have not yet been investigated. In melanoma, we correlated their expression with conventional histopathologic prognostic factors.

Nucleolin protein expression in cutaneous melanocytic lesions.

Background: Nucleolin is a major nucleolar argyrophilic protein involved in carcinogenesis. There are only few studies on its tissue expression in human cancer and none in melanoma. We aimed at exploring this protein and its prognostic impact in cutaneous melanocytic lesions.

Efficacy of cyclosporine A treatment in relapsing febrile lobular panniculitis associated with small vessel vasculitis.

Weber-Christian Disease (WCD), also known as relapsing febrile lobular non-suppurative panniculitis, is a rare condition characterized by recurrent subcutaneous inflammatory nodules in the adipose tissue in addition to fever, malaise and other systemic manifestations such as polyarthralgia and polymyalgia. The association with small vessel vasculitis has been rarely reported. We report here an unusual case of WCD associated with small vessels vasculitis also describing the efficacy of Cyclosporin A treatment.

Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases.

The management of unresectable metastatic melanoma is a major clinical challenge because of the lack of reliably effective systemic therapies. Blocking cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) has recently been proposed as a strategy to enhance cell-mediated immune responses to cancer, and clinical trials have demonstrated that anti-CTLA-4 therapy can produce durable outcomes with different response patterns than cytotoxic chemotherapy. We enrolled eight out of 155 patients with advanced melanoma in a multicentre phase II trial that evaluated the activity and tolerability of ipilimumab, a fully human, anti-CTLA-4 monoclonal antibody ( www.

Utility of tumour-infiltrating CD25+FOXP3+ regulatory T cell evaluation in predicting local recurrence in vertical growth phase cutaneous melanoma.

Tumour-infiltrating lymphocytes (TILs) represent the local immune response to cancer, however, their correlation with tumour behaviour is not unanimously considered in the literature. Most studies have not characterized TILs, that are known to comprise distinct subsets, bearing different roles in the complex tumour microenvironment. Characterization of patient lymphocytes has been mainly performed in peripheral blood, that is not always representative of the local immune status.

Macrophage migration inhibitory factor protein and mRNA expression in cutaneous melanocytic tumours.

Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in various biological processes. Although MIF's functions in cancer have not been completely elucidated, its expression has usually been correlated with tumour progression and aggressiveness, and it is currently discussed as a new promising target for novel therapies. Recent studies seem to confirm its active role in melanoma pathobiology; however, its expression has not yet been extensively studied in melanocytic tumours.

Classification and pathophysiology of skin grafts.

Flaps and grafts are the 2 main surgical procedures to repair losses of skin tissue. A flap is a full-thickness portion of skin sectioned and isolated peripherally and in depth from the surrounding skin, except along one side, called the peduncle. A graft is a section of skin, of variable thickness and size, completely detached from its original site and moved to cover the zone to be repaired.

Acral malignant melanoma and striated palmoplantar keratoderma (Brunauer-Fohs-Siemens syndrome): a fortuitous association?

Background: Striated palmoplantar keratoderma or Brunauer-Fohs-Siemens syndrome is a very rare, focal, nonepidermolytic palmoplantar keratoderma with autosomal inheritance. Unlike other palmoplantar keratodermas, no association with visceral or skin cancer has ever been reported.

Objective: We report a case of malignant melanoma arising in the hyperkeratotic lesions on the right heel of a patient with striated palmoplantar keratoderma.

Skin allograft in the treatment of toxic epidermal necrolysis (TEN).

Background: TEN is a severe form of exfoliative dermatitis. Its course is acute and its outcome fatal in 40% of cases. Wound cover to prevent fluid/protein loss and infections and to control pain, is the first step, as for burns.