Background: Survival rates among childhood cancer survivors (CCS) have enormously increased in the last 40 years. However, this improvement has been achieved at the expense of serious late effects that frequently involve the endocrine system. Aim: To evaluate the cumulative incidence of endocrine diseases in a cohort of long-term CCS. Materials and methods: We analyzed the clinical data of 310 adults, followed for a median time of 16.0 years after the first cancer diagnosis. The monitoring protocols applied to each patient were personalized on the basis of cancer diagnosis and previous treatments, according to the Children's Oncology Group guidelines. Results: The cumulative incidence of endocrine late effects steadily increased over time. At the last follow-up visit available, 48.46% of females and 62.78% of males were affected by at least one endocrine disease. The most common disorders were gonadal dysfunction, primary hypothyroidism, and GH deficiency (GHD). The main risk factors for endocrine disease were male sex (hazard ratio (HR)Z1.45, 95% confidence interval (95% CI) 1.05-1.99), radiotherapy (HRZ1.91, 95% CI 1.28-2.84), hematopoietic stem cells transplantation (HRZ3.11, 95% CI 2.23-4.34), and older age at cancer diagnosis (HRZ1.89, 95% CI 1.25-2.85). Male sex was associated with a higher risk of gonadal disorders, whereas radiotherapy specifically increased the risk of GHD and thyroid dysfunction. Conclusions: Endocrine disorders among CCS have a high prevalence and increase over time. Thus, endocrinologists need to cope with an increasing demand for health care in a field that is still little developed and that, in perspective, could also be extended to some selected types of adult cancer survivors.

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In poorly differentiated thyroid cancer, molecular characteristics are reported to be lost such as to cause insensitivity of the tumor to radiometabolic therapy. Considerable work is in progress to identify compounds that redifferentiate thyroid cancer cells. The present study evaluates the action of valproic acid, a potent anticonvulsant recently reported to inhibit histone deaceytlase, on cultured thyroid cancer cells. N-PA (poorly differentiated) and ARO (anaplastic) cells were treated with increasing valproic acid concentrations.; expression of mRNA and cell localization pattern for the Na+/I- symporter (NIS), as well as 125I uptake, were evaluated before and after treatment. Valproic acid induced NIS gene expression, NIS membrane localization and iodide accumulation in N-PA cells; it was effective at clinically-safe doses in the therapeutic range. In ARO cells, only induction of NIS mRNA was observed, and was not followed by any change in iodide uptake. Valproic acid is thus effective at restoring the ability of N-PA cells to accumulate iodide and its use in clinical trials may be recommended.

Objective: Treatment options for anaplastic thyroid carcinoma (ATC), which is one of the most lethal human malignant tumors, include surgery, chemotherapy and radiotherapy usually combined in a multimodal approach, to improve survival and avoid death from local invasion. However, there is no standard protocol for ATC treatment and the optimal sequence within multimodal therapy is debated. We retrospectively report the clinical outcome of 30 ATC patients referred consecutively to the Oncological Endocrinology Unit of San Giovanni Battista Hospital (Turin, Italy) between 2000 and 2005. Design: Patients were treated by one of the following approaches: i) surgery followed by adjuvantcombined chemoradiotherapy; ii) neo-adjuvant chemoradiotherapy followed by surgery and adjuvant chemotherapy; or iii) chemotherapy alone. The surgical procedures were classified as 'maximal debulking' or 'palliative resection'. Maximal debulking entailed total or near-total thyroidectomy and complete resection of all gross tumor or minimal residual disease adherent to vital structures, independently of the presence or absence of distant metastases. In palliative resections, macroscopic residual disease was left in the neck. Survival of patients stratified by treatment was assessed. Results: Analysis of multivariate hazard ratios showed that maximal debulking followed by adjuvant chemoradiotherapy was the only treatment that modified survival of ATC patients (hazard ratioZ 0.23, 95% CI: 0.07-0.79), even if factors determining poor prognosis or increased surgical risk were present. Conclusions: Despite the overall grim outcome of ATC, these results justify an attempt at maximal debulking surgery, followed by adjuvant chemoradiotherapy, possibly in all ATC patients. 156 425-430 European Journal of Endocrinology

Early "maximal debulking," followed by adjuvant therapy, can improve the survival and ameliorate the quality of residual life preventing the risk of suffocation. This effect is also observed in patients with distant metastasis at diagnosis and treated with this approach: they have an outcome similar to that observed in stage IV-B patients. We thus suggest that surgery may be considered in the management of all ATC patients, and should not be restricted a priori to stages IV-A and IV-B.