The Role of the Kinase Inhibitors in Thyroid Cancers.

Thyroid cancer is the most common endocrine malignancy, accounting for about 3% of all cancer cases each year worldwide with increasing incidence, but with the mortality remaining stable at low levels. This contradiction is due to overdiagnosis of indolent neoplasms identified by neck ultrasound screening that would remain otherwise asymptomatic. Differentiated thyroid carcinomas (DTCs) are almost curable for 95% with a good prognosis. However, 5% of these tumours worsened toward aggressive forms: large tumours with extravasal invasion, either with regional lymph node or distant metastasis, that represent a serious clinical challenge. The unveiling of the genomic landscape of these tumours shows that the most frequent mutations occur in tyrosine kinase receptors (RET), in components of the MAPK/PI3K signalling pathway (RAS and BRAF) or chromosomal rearrangements (RET/PTC and NTRK hybrids); thus, tyrosine-kinase inhibitor (TKI) treatments arose in the last decade as the most effective therapeutic option for these aggressive tumours to mitigate the MAPK/PI3K activation. In this review, we summarize the variants of malignant thyroid cancers, the molecular mechanisms and factors known to contribute to thyroid cell plasticity and the approved drugs in the clinical trials and those under investigation, providing an overview of available treatments toward a genome-driven oncology, the only opportunity to beat cancer eventually through tailoring the therapy to individual genetic alterations. However, radiotherapeutic and chemotherapeutic resistances to these anticancer treatments are common and, wherever possible, we discuss these issues.

Evaluation of a Novel Cone Beam Computed Tomography Scanner for Bone Density Examinations in Preoperative 3D Reconstructions and Correlation with Primary Implant Stability.

BACKGROUND: Bone density examination (BDE) using preoperative cone beam computed tomography (CBCT) might be used to predict primary implant stability in implant patients. PURPOSE: The aim of the study was to validate a novel CBCT scanner in vitro with regard to BDE in preoperative scans and to analyze the in vivo correlation of CBCT scan results with primary implant stability measurements. MATERIALS AND METHODS: A CBCT scanner was validated in vitro with regard to spatial uniformity and linearity of CT numbers (Hounsfield units, HU) by using a series of phantoms and plastic and hydroxyapatite specimens of various densities. Forty-nine patients (27 female and 22 male, mean age 55.6 ± 9.8) were scanned prior to and 1 to 6 months after the placement of 155 dental implants of different lengths and diameters. Mean and peak insertion torque (IT) in Ncm were registered during implant placement. Resonance frequency analysis (RFA) measurements in ISQ units were performed after placement. The second scan was used to export and superimpose the exact positions of bone and implants into the first scan. Virtual probes with the same length as the actual implant were automatically placed at the implant sites, and mean HU values were measured in a 1 mm-wide circular corridor from the tip of the threads and out. RESULTS: The in vitro validation showed high uniformity and linearity of CT numbers (HU). The clinical study showed significant correlations between bone density and ISQ, mean IT, and peak IT, respectively. CONCLUSIONS: The WhiteFox CBCT scanner measures bone density with high accuracy. There is a correlation between bone density and primary implant stability as assessed with IT and RFA measurements. The findings suggest that BDE may be used as an additional feature in treatment-planning software to estimate primary stability at predetermined implant sites.

Medullary thyroid cancer secreting carbohydrate antigen 19-9 (Ca 19-9): a fatal case report.

BACKGROUND: During follow-up for patients with medullary thyroid cancer (MTC), the levels of serum calcitonin and carcinoembryonic antigen are important, and the doubling time of these biomarkers significantly correlates with disease progression. Other antigens are present in tumor tissue and the sera of patients with MTC, but there are scarce published data on the serum levels of carbohydrate antigen 19-9 (Ca 19-9), a tumor marker primarily used for the diagnosis and follow-up of pancreatic and gastrointestinal neoplasias. Recently, the case of a 56-year-old woman with multiple endocrine neoplasia type 2B with high serum levels of Ca 19-9 was reported; this patient experienced rapid disease progression that led to her death. CASE PRESENTATION: A 28-year-old man was referred to the Department of Endocrinology of the University Hospital of Pisa with suspected MTC with laterocervical lymph node metastasis, a single liver lesion (10 mm), several bone metastases, and bilateral pheochromocytomas. RET genetic testing revealed a germline Cys634Arg mutation. During the hospitalization, the carcinoembryonic antigen and Ca 19-9 levels increased while the calcitonin concentration remained stable; despite the apparent stability of the lesions, the condition of the patient worsened rapidly and resulted in death. CONCLUSIONS: High levels of serum Ca 19-9 could be considered a marker of the dedifferentiation of MTC and disease aggressiveness, but additional data on the association between Ca 19-9 and advanced MTC are required to confirm this hypothesis.

IGF-II mRNA expression in breast cancer: predictive value and relationship to other prognostic factors.

PURPOSE: Insulin-like growth factor-II (IGF-II) is an important regulator of tumor growth in breast cancer. In this study we have examined the prognostic value of IGF-II mRNA expression in breast cancer and its relationship to other predictive parameters. PATIENTS: Sixty-eight women with infiltrating ductal carcinoma were given the same treatments including mastectomy and antitumoral therapies and followed up for 5 years. RESULTS: The overall 5-year survival rate was 73.5% (55/68). IGF-II mRNA was expressed in 33/64 patients (51.6%) and had no significant impact on survival. The expression of estrogen receptor (ER) and progesterone receptor (PgR) did not significantly affect the 5-year survival, but in the presence of an IGF-II mRNA signal, the survival of ER- and PgR-negative patients (n=9) was lower than that of ER- and PgR-positive patients (n=15), although the difference was not significant. The 5-year survival was not significantly different between Ki-67-positive and negative patients, but in the IGF-II positive group Ki-67-positive patients (n=7) had a significantly poorer prognosis than Ki-67-negative patients (n=26). The expression of p53 protein was associated with a poorer prognosis: 6/11 (54.5%) p53-positive patients died in the first 26 months of follow-up and 5 of these 6 patients (83.3%) also had positive IGF-II mRNA expression. CONCLUSIONS: IGF-II mRNA expression per se is not an independent predictive factor in breast cancer but may be a marker of poor prognosis when associated with other prognostic factors such as Ki-67 index and p53 expression.