Anaplastic thyroid carcinoma

Abstract Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1-2% of thyroid malignancies and it accounts for 14-39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85-100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6\u2009months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs

Postoperative insulin-like growth factor 1 levels reflect the graft's function and predict survival after liver transplantation

Background The reduction of insulin-like growth factor 1 (IGF-1) plasma levels is associated with the degree of liver dysfunction and mortality in cirrhotic patients. However, little research is available on the recovery of the IGF-1 level and its prognostic role after liver transplantation (LT). Methods From April 2010 to May 2011, 31 patients were prospectively enrolled (25/6 M/F; mean age +/- SEM: 55.2 +/- 1.4 years), and IGF-1 serum levels were assessed preoperatively and at 15, 30, 90, 180 and 365 days after transplantation. The influence of the donor and recipient characteristics (age, use of extended criteria donor grafts, D-MELD and incidence of early allograft dysfunction) on hormonal concentration was analyzed. The prognostic role of IGF-1 level on patient survival and its correlation with routine liver function tests were also investigated. Results All patients showed low preoperative IGF-1 levels (mean +/- SEM: 29.5 +/- 2.1), and on postoperative day 15, a significant increase in the IGF-1 plasma level was observed (102.7 +/- 11.7 ng/ml; p65 years) or extended criteria donor grafts. An inverse correlation between IGF-1 and bilirubin serum levels at day 15 (r = -0.3924, p = 0.0320) and 30 (r = -0.3894, p = 0.0368) was found. After multivariate analysis, early (within 15 days) IGF-1 normalization [Exp(b) = 3.913; p = 0.0484] was the only prognostic factor associated with an increased 3-year survival rate. Conclusion IGF-1 postoperative levels are correlated with the graft's quality and reflect liver function. Early IGF-1 recovery is associated with a higher 3-year survival rate after LT

(A) Serum levels of growth hormone (GH) and (B) insulin-like growth factor 1 (IGF-1) before and after liver transplantation.

<p>Values are expressed as the mean ± standard error of the mean. Student’s t test for paired samples was employed to investigate significant differences in hormonal values over time. * p <0.05 compared with the previous value; ^<b>Ω</b> p <0.01 compared with the pre-LT value. <b>Abbreviations:</b> IGF-1, insulin-like growth factor 1; LT, liver transplantation; GH, growth hormone.</p

Actual 3-year survival analysis in patients showing normal (solid line) or low (dotted line) IGF-1 plasma levels on postoperative day 15.

<p>Survival differences were investigated by the Log Rank test. <b>Abbreviations:</b> IGF-1, insulin-like growth factor 1; LT, liver transplantation; POD, postoperative day.</p

Univariate and multivariate analysis of risk factors affecting patient survival.

<p>IGF-1, insulin-like growth factor 1; LT, liver transplantation; ECD, extended criteria donor; DMELD, donor age x Model for End Stage Liver Disease; EAD, early allograft dysfunction; DRI, Donor Risk Index; HCV, hepatitis C virus; HCC, hepatocellular carcinoma; POD, postoperative day.</p

Differences in insulin-like growth factor 1 (IGF-1) serum levels after liver transplantation according to (A) donor age and (B) extended criteria donor (ECD) score.

<p>Values are expressed as the mean ± standard error of the mean. Student’s t test for unpaired samples was employed to investigate significant differences between hormonal values at different time points. <b>Abbreviations:</b> IGF-1, insulin-like growth factor 1; LT, liver transplantation; ECD, extended criteria donor.</p

Baseline recipients’ and donors’ characteristics.

<p>Continuous values are expressed as the mean ± standard error of the mean. LT, liver transplantation; MELD, Model for End-Stage Liver Disease; PBC, primary biliary cirrhosis; ECD, extended criteria donor; DMELD, donor age x recipient MELD.</p