The role of micrometastasis in high-risk skin cancers.

The propensity to metastasize is the most important prognostic indicator for solid cancers. New insights into the mechanisms of early carcinogenesis have revealed micrometastases are generated far earlier than previously thought. Evidence supports a synergistic relationship between vascular and lymphatic seeding which can occur before there is clinical evidence of a primary tumour. Early vascular seeding prepares distal sites for colonisation while regional lymphatics are co-opted to promote facilitative cancer cell mutations. In response, the host mounts a global inflammatory and immunomodulatory response towards these cells supporting the concept that cancer is a systemic disease. Cancer staging systems should be refined to better reflect cancer cell loads in various tissue compartments while clinical perspectives should be broadened to encompass this view when approaching high-risk cancers. Measured adjunctive therapies implemented earlier for low-volume, in-transit cancer offers the prospect of preventing advanced disease and the need for heroic therapeutic interventions. This review seeks to re-appraise how we view the metastatic process for solid cancers. It will explore in-transit metastasis in the context of high-risk skin cancer and how it dictates disease progression. It will also discuss how these implications will influence our current staging systems and its consequences on management.

A review of actinic keratosis, skin field cancerisation and the efficacy of topical therapies.

While a wide range of treatments exist for actinic keratosis and skin field cancerisation, the long-term benefits of the most common topical therapies are poorly defined. This report reviews the efficacy of the most commonly used topical therapies to treat regional or field lesions. Limited clinical and histopathological data are available on clearance rates at 12 months post-treatment for the most commonly used agents, with varied outcome measures making any comparison difficult. In general, total field clearance rates at 12 months are suboptimal for the most commonly employed agents. Given the increasing incidence of actinic keratosis and skin field cancerisation due to an ageing population, further research into the efficacy of therapies is critical to guide treatment choice.

Preventing a drop in effective plasma osmolality to minimize the likelihood of cerebral edema during treatment of children with diabetic ketoacidosis.

OBJECTIVES: To test whether a drop in effective plasma osmolality (P(Eff osm); 2 x plasma sodium [P(Na)] + plasma glucose concentrations) during therapy for diabetic ketoacidosis (DKA) is associated with an increased risk of cerebral edema (CE), and whether the development of hypernatremia to prevent a drop in the P(Eff osm) is dangerous. STUDY DESIGN: This study is a retrospective comparison of a CE group (n = 12) and non-CE groups with hypernatremia (n = 44) and without hypernatremia (n = 13). RESULTS: The development of CE (at 6.8 +/- 1.5 hours) was associated with a drop in P(Eff osm) from 304 +/- 5 to 290 +/- 5 mOsm/kg (P < .001). Control patients did not show this drop in P(Eff osm) at 4 hours (1 +/- 2 and 2 +/- 2 vs -9 +/- 2 mOsm/kg; P < .01), because of a larger rise in P(Na) and/or a smaller drop in plasma glucose. During this period, the CE group received more near-isotonic fluids (69 +/- 9 vs 35 +/- 2 and 27 +/- 3 mL/kg; P < .001). The CE group had a higher mortality (3/12 vs 0/57; P = .003), and more neurologic sequelae (5/12 vs 1/57; P < .001). CONCLUSIONS: CE during therapy for DKA was associated with a drop in P(Eff osm). An adequate rise in P(Na) may be needed to prevent this drop in P(Eff osm).