Thyroid-hormone therapy and thyroid cancer: a reassessment.

Experimental studies and clinical data have demonstrated that thyroid-cell proliferation is dependent on thyroid-stimulating hormone (TSH), thereby providing the rationale for TSH suppression as a treatment for differentiated thyroid cancer. Several reports have shown that hormone-suppressive treatment with the L-enantiomer of tetraiodothyronine (L-T(4)) benefits high-risk thyroid cancer patients by decreasing progression and recurrence rates, and cancer-related mortality. Evidence suggests, however, that complex regulatory mechanisms (including both TSH-dependent and TSH-independent pathways) are involved in thyroid-cell regulation. Indeed, no significant improvement has been obtained by suppressing TSH in patients with low-risk thyroid cancer. Moreover, TSH suppression implies a state of subclinical thyrotoxicosis. In low-risk patients, the goal of L-T(4) treatment is therefore to obtain a TSH level in the normal range (0.5-2.5 mU/l). Only selected patients with high-risk papillary and follicular thyroid cancer require long-term TSH-suppressive doses of L-T(4). In these patients, careful monitoring is necessary to avoid undesirable effects on bone and heart

A qualitative view of cryogenic fluid injection into high speed flows

The injection of supercritical pressure, subcritical temperature fluids, into a 2-D, ambient, static temperature and static pressure supersonic tunnel and free jet supersonic nitrogen flow field was observed. Observed patterns with fluid air were the same as those observed for fluid nitrogen injected into the tunnel at 90 deg to the supersonic flow. The nominal injection pressure was of 6.9 MPa and tunnel Mach number was 2.7. When injected directly into and opposing the tunnel exhaust flow, the observed patterns with fluid air were similar to those observed for fluid nitrogen but appeared more diffusive. Cryogenic injection creates a high density region within the bow shock wake but the standoff distance remains unchanged from the gaseous value. However, as the temperature reaches a critical value, the shock faded and advanced into the supersonic stream. For both fluids, nitrogen and air, the phenomena was completely reversible

Efficacy and safety of vandetanib in progressive and symptomatic medullary thyroid Cancer: Post hoc analysis from the ZETA trial

PURPOSE We conducted a post hoc analysis of the vandetanib phase III trial involving patients with advanced medullary thyroid cancer (MTC) to assess the efficacy and safety of vandetanib in patients with progressive and symptomatic MTC. The primary objective of the analysis was to determine progression-free survival (PFS) of these patients. PATIENTS AND METHODS Eligible patients from the ZETA trial were divided into 4 disease severity subgroups: progression and symptoms, symptoms only, progression only, and no progression and no symptoms assessed at baseline. PFS, determined from objective tumor measurements performed by the local investigator, overall survival (OS), time to worsening of pain (TWP), and objective response rate (ORR) were evaluated. RESULTS Of the 331 patients in this trial, 184 had symptomatic and progressive disease at baseline. In this subgroup, results were similar in magnitude to those observed in the overall trial for PFS (hazard ratio [HR], 0.43; 95% CI, 0.28 to 0.64; P, .0001), OS (HR, 1.08; 95% CI, 0.72 to 1.61; P 5 .71), and TWP (HR, 0.67; 95% CI, 0.43 to 1.04; P 5 .07), and the observed adverse events were consistent with the known safety profile of vandetanib. In this subgroup, the ORR was 37% in the treatment arm versus 2% in the placebo arm. CONCLUSION Vandetanib demonstrated clinical benefit—specifically, increased PFS—in patients with symptomatic and progressive MTC

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected

Developing a framework for the assessment of current and future flood risk in Venice, Italy

Flooding causes serious impacts on the old town of Venice, its residents, and its cultural heritage. Despite this existence-defining condition, limited scientific knowledge on flood risk of the old town of Venice is available to support decisions to mitigate existing and future flood impacts. Therefore, this study proposes a risk assessment framework to provide a methodical and flexible instrument for decision-making for flood risk management in Venice. We first use a state-of-the-art hydrodynamic urban model to identify the hazard characteristics inside the city of Venice. Exposure, vulnerability, and corresponding damage are then modeled by a multi-parametric, micro-scale damage model which is adapted to the specific context of Venice with its dense urban structure and high risk awareness. Furthermore, a set of individual protection scenarios are implemented to account for possible variability in flood preparedness of the residents. This developed risk assessment framework was tested for the flood event of 12 November 2019 and proved able to reproduce flood characteristics and resulting damage well. A scenario analysis based on a meteorological event like 12 November 2019 was conducted to derive flood damage estimates for the year 2060 for a set of sea level rise scenarios in combination with a (partially) functioning storm surge barrier, the Modulo Sperimentale Elettromeccanico (MOSE). The analysis suggests that a functioning MOSE barrier could prevent flood damage for the considered storm event and sea level scenarios almost entirely. A partially closed MOSE barrier (open Lido inlet) could reduce the damage by up to 34 % for optimistic sea level rise prognoses. However, damage could be 10 % to 600 % higher in 2060 compared to 2019 for a partial closure of the storm surge barrier, depending on different levels of individual protection.</p