The role of multidisciplinary approach in the clinical management of differentiated thyroid cancer

Thyroid cancer is, in general, the most frequent endocrinological neoplasm, characterized however by an extremely low mortality rate, morbidity and persistence of disease. This is due in part to the often indolent nature of the disease, but also to the ever increasing appropriateness of primary treatments, often capable of eradicating the disease in the face of low burdens of adverse events. The availability of increasingly targeted approaches to the specific condition of the individual patient makes it necessary for shared management among the various specialist figures involved in the treatment of the pathology. During the PhD course, some of the issues relating to multidisciplinary management and the integration of skills in the diagnostic-therapeutic pathway of thyroid cancer were studied, from the initial stages to the treatment of advanced disease. After the diagnosis, the surgical approach represents the first line of treatment of the disease. Over the last few years, the use of increasingly less invasive techniques has made it possible to reduce adverse events and complications. However, this must be based on a correct classification and estimation of the risk of recurrence. In particular, papillary microcarcinoma (mPTC) has demonstrated a particularly indolent behavior and a minimal recurrence rate. In this sense, we evaluated a cohort of patients affected by mPTC and studied the factors that could predict its recurrence and therefore be considered in the treatment definition. Following surgery, the need for radioiodine therapy (RAI), aimed at identifying and selectively targeting any residual thyroid tissue, must also be evaluated on the basis of the characteristics of the surgically removed disease and the available clinical and biochemical parameters post-surgery. Close cooperation between the endocrinologist, pathologist and nuclear doctor is therefore mandatory. From this point of view, we considered the impact of minimal extrathyroidal extension (understood as microscopic invasion beyond the organ capsule) of differentiated thyroid cancer (DTC) on the risk of recurrence, finding that this does not significantly change the risk of recurrence. Another retrospective study was also conducted in order to compare the efficacy and adverse events of RAI performed at standard doses with that at low doses. The latter, now widely approved in patients at low and sometimes intermediate risk of recurrence, has confirmed excellent efficacy data, showing a slightly superior clinical tolerability profile and no significant changes from the haematochemical point of view compared to the standard treatment. An important aspect in the management of patients with thyroid cancer, given the excellent response rate to primary treatments, is represented by the long-term follow-up and the prevention of complications, from an endocrine point of view but above all from a cardiovascular point of view. In this sense, in addition to investigating the association between thyroid cancer and other endocrine pathologies such as hyperparathyroidism, which has demonstrated an independent impact on the patient's prognosis, we evaluated the incidence and possible predictive factors of cardiovascular events in a DTC population with at least 5 years of follow-up, confirming the role of careful cardiovascular evaluation, especially in patients maintained in TSH suppression. Furthermore, the incidence of vascular events, specifically those of a thromboembolic nature (TEE), was also studied in the context of advanced and iodine-refractory thyroid cancer, initially in a small cohort of patients receiving tyrosine inhibitor therapy. kinase, thus evaluating the possible predictive factors of TEE within a court of patients affected by advanced cancer. Finally, with regard to the treatment of advanced and iodine-refractory thyroid cancer, the cooperation of diversified professional figures appears essential, given the great development in this context of target-therapies aimed at the specific typology and mutational profile of the disease. In this regard, a limited case series of patients subjected to mutational and immunohistochemical analysis was retrospectively analysed, confirming the importance of the BRAF, TERT genes and PDL1 expression in defining the prognostic picture and possible therapeutic approaches. Also for these patients, the comparison between the endocrinologist and the nuclear doctor is necessary in order to integrate conventional radiology data with information deriving from functional imaging such as PET with FDG, in order to study the initial prognosis, the progress of the disease and the response to different treatment regimens

DNA wrapping around MWNTs and graphene: a SERS study

In recent years, carbon nanostructure as nanotubes (CNTs) and graphene are at the centre of a significant research effort due to the strong scientific and technological interest because of their unique physical and chemical properties: large surface area, excellent thermal and electric conductivity, high electron transfer kinetics and strong mechanical strength. Recently, a great attention has been paid to the interaction of DNA with carbon-based nanostructures such as C60, multiwalled-nanotubes (MWNTs), single-walled nanotubes (SWNTs) and graphene. The development of these studies is motivated by a wide spectrum of possible use of these materials e.g. as biosensors, drug delivery agents and diagnosis tools. In this work, we applied surface-enhanced Raman spectroscopy (SERS) to the study of DNA/MWNTs and DNA/graphene systems

Role of Strain Elastography and Shear-Wave Elastography in a Multiparametric Clinical Approach to Indeterminate Cytology Thyroid Nodules

BACKGROUND In thyroid nodules with indeterminate cytology, further clinical assessment aimed at ruling out malignancy is often mandatory. Ancillary imaging techniques and genetic mutation analysis can improve the risk stratification of such lesions, thereby facilitating the clinician's decision to undertaken surgery or simple follow-up. The aim of this study was to evaluate the diagnostic performance of shear-wave elastography (SW), strain elastography (ELX 2/1), conventional ultrasound (US), contrast-enhanced ultrasound (CEUS), and BRAF V600E mutation analysis in the aforementioned lesions. MATERIAL AND METHODS We enrolled 81 patients, each with 1 indeterminate-cytology thyroid nodule. Thyroid function, thyroperoxidase antibodies and calcitonin were known in each case. SW, ELX 2/1, US, CEUS, and BRAF mutation analysis were subsequently performed, followed by a second FNAB. If the lesion was not downgraded to benign, surgery was recommended and histological reports collected. RESULTS There were 28 nodules (34%) that proved benign on the second FNAB; 38 nodules (47%) underwent surgery (17 benign, 21 malignant), and 15 nodules (19%) refused surgery. The only techniques related to histological outcome were US (AUC=0,766), ELX 2/1 (AUC=0.701), and BRAF analysis (AUC=0.762). ELX 2/1 and SW reports were not correlated with each other (P=0.45). A scoring system taking into account all the variables considered performed better than the single variables alone (AUC=0.831). CONCLUSIONS In indeterminate-cytology thyroid lesions, repeating FNAB can avoid unnecessary surgery. ELX 2/1 seems to perform better than SW in distinguishing malignancy; these techniques could, however, be complementary in describing such lesions. A multiparametric approach appears the most accurate in predicting nodule histology

Detection of Polyethylene Glycol Thyrotropin (TSH) Precipitable Percentage (Macro-TSH) in Patients with a History of Thyroid Cancer

Background: Owing to its large molecular size, polyethylene glycol (PEG)-precipitable thyrotropin (TSH) can accumulate in the circulation, elevating TSH levels. PEG-precipitable TSH can be used to detect macro-TSH (mTSH) in serum. Our aim was to evaluate the prevalence of mTSH in patients who had undergone thyroidectomy for thyroid cancer.Methods: Seventy-three thyroid cancer patients and 24 control subjects on levothyroxine (LT4) TSH-suppressive or replacement therapy were evaluated. Screening for mTSH was performed by adding PEG to serum in order to precipitate.-globulin. A percentage of PEG-precipitable TSH >= 80% was considered suggestive of mTSH.Results: No correlation between free-T4 (fT4) and TSH levels was found. PEG-precipitable TSH was 39.3%+/- 1.9% in thyroid cancer patients and 44.1%+/- 3.9% in controls. Macro-TSH was deemed to be present in one thyroid cancer patient and in two control subjects. Only in the thyroid cancer group was PEG-precipitable TSH found to be negatively correlated with fT4 concentration. No correlation was found between PEG-precipitable TSH and other clinical conditions in any patients.Conclusion: The presence of mTSH seems to be a rare phenomenon in thyroid cancer. In some patients with low PEG-precipitable TSH, a reduction in LT4 dosage could be suggested. LT4 dosage adjusted to body weight is the main factor in maintaining TSH in a semi-suppressed or normal range. Evaluation of mTSH could be necessary in patients in whom a balance is required between adequate TSH suppression and the avoidance of unnecessary exogenous hyperthyroxinemia

Tramadol/dexketoprofen (TRAM/DKP) compared with tramadol/paracetamol in moderate to severe acute pain: results of a randomised, double-blind, placebo and active-controlled, parallel group trial in the impacted third molar extraction pain model (DAVID study)

Objectives: To compare efficacy/safety of oral tramadol 75 mg/dexketoprofen 25 mg (TRAM/DKP) and TRAM 75 mg/paracetamol 650 mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar. Design: Multicentre, randomised, double-blind, placebo-controlled, phase IIIb study. Participants: Healthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis. Interventions: Surgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (≥4) within 4 hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25 mg, TRAM/paracetamol 75/650 mg or placebo. Main outcome measures: Efficacy was based patients' electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0='no relief', 1='a little (perceptible) relief', 2='some (meaningful) relief', 3='lot of relief', 4='complete relief') at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6 hours (TOTPAR6). Rescue medication was available during the treatment period. Results: TRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.2 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups. Conclusions: TRAM/DKP (75/25 mg) is effective and superior to TRAM/paracetamol (75/650 mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile

Wavelength Division Demultiplexing and Cross-Talk Assessment of a Photonic Crystal Filter

International audienceWe report on the design, fabrication and characterization of a filter for demultiplexing in the wavelength division domain realized with a H0 cavity on a III-V photonic crystal (PhC) membrane. This device is single mode, the total insertion losses are about 10.5 dB, the drop efficiency is close to 40 % and the channel isolation can exceed 20 dB at 500 GHz. 28 Gbit/s NRZ wavelength demultiplexing shows less than 0.5 dB penalties. Cross talk measurements demonstrate less than 1 dB penalty when adjacent channels are spaced as closely as 235 GHz, demonstrating the good compatibility of this filter with LAN-WDM systems. Finally, 56 Gbit/s NRZ-DQPSK signal filtering is assessed revealing negligible penalty (< 0.5 dB)