Osteonecrosis of the jaw: a rare but possible side effect in thyroid cancer patients treated with tyrosine-kinase inhibitors and bisphosphonates.

Osteonecrosis of the jaw (ONJ) is a rare but very serious disease that can affect both jaws. It is defined as exposed bone in the maxillofacial region that does not heal within 8 weeks after a health care provider identification. ONJ can occur spontaneously or can be due to drugs like bisphosphonates (BPS) and anti-RANK agents, in patients with no history of external radiation therapy in the craniofacial region. Although in phase 3 trials of tyrosine kinase inhibitors (TKIs) used in thyroid cancer (TC) the ONJ was not reported among the most common side effects, several papers reported the association between ONJ and TKIs, both when they are used alone and in combination with a bisphosphonate. The appearance of an ONJ in a patient with metastatic radio-iodine refractory differentiated TC, treated with zoledronic acid and sorafenib, has put us in front of an important clinical challenge: when a ONJ occurred during TKIs treatment, it really worsens the patients' quality of life. We should consider that in the case of ONJ a TKI discontinuation becomes necessary, and this could lead to a progression of neoplastic disease. The most important aim of this review is to aware the endocrinologists/oncologists dealing with TC to pay attention to this possible side effect of BPS and TKIs, especially when they are used in association. To significantly reduced the risk of ONJ, both preventive measures before initiating not only antiresorptive therapy but also antiangiogenic agents, and regular dental examinations during the treatment should always be proposed.

I fear COVID but diabetic foot (DF) is worse: a survey on patients' perception of a telemedicine service for DF during lockdown.

AIMS: To evaluate the patients' perceptions of telemedicine visits during COVID-19 lockdown and their level of anxiety about COVID and diabetic foot (DF). METHODS: In May 2020, we contacted by phone all the patients who underwent in March and April to remote monitoring visits for DF during the lockdown for COVID-19, with a structured interview, focusing on their perceptions about telemedicine service for DF and on the anxiety toward COVID and DF. RESULTS: We analyzed 257 remote monitoring visits in 211 patients. Two hundred and six patients answered the follow-up interview; 177 patients (85.9%) remembered the monitoring visit, 140 (67.9%) the health care professional and 181 patients (87.9%) the reason of contact; 169 patients were alone during the visit, 37 with a relative. Patients judged useful both the monitoring during pandemic (4.35 ± 0.28 on a maximum of five) and the possibility to continue after the lockdown (4.34 ± 0.23 on a maximum of five). Eventually, we observed that DF patients were more worried by DF than by COVID on a scale from 0 (not fear at all) to 5 (terrified) (4.79 ± 0.05 vs. 3.27 ± 1.03, p < 0.05). This difference was higher in previously ulcerated patients (4.84 ± 0.03 vs. 3.03 ± 1.13, p < 0.05) and even more in amputees (4.93 ± 0.03 vs. 2.73 ± 1.21, p < 0.05). CONCLUSIONS: DF patients appreciated televisits during lockdown and the continuation of this service after its end. In this context DF prevails on COVID in the worries of patients, especially if they are recurrent ones.

Targeted Therapy in Thyroid Cancer: State of the Art.

Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC). In the last few years, several TKIs have been tested for the treatment of advanced, progressive and RAI-R thyroid cancers and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC; vandetanib and cabozantinib for MTC. The objective of this overview is to present the current status of the treatment of advanced DTC, MTC, PDTC and ATC with the use of TKIs by describing the benefits and the limits of their use. A comprehensive analysis and description of the molecular basis of these drugs and the new therapeutic perspectives are also reported. Some practical suggestions are also given for the management to the potential side-effects of these drugs.

Classical point mutations of RET, BRAF and RAS oncogenes are not shared in papillary and medullary thyroid cancer occurring simultaneously in the same gland.

BACKGROUND: Papillary (PTC) and medullary (MTC) thyroid carcinomas represent two distinct entities, but quite frequently, they may occur simultaneously. AIM: To provide genetic analysis of PTC and MTC occurring in the same patient (PTC/MTC) to elucidate their origin. METHODS: Sequencing analysis of RAS, BRAF and RET oncogenes hot spots mutations in tumoral and normal tissues of 24 PTC/MTC patients. RESULTS: Two of 24 patients (8.3 %) were affected by familial MTC (FMTC) harboring RET germline mutations in all tissues. Eight of 22 (36.4 %) sporadic cases did not show any somatic mutation in the three tissue components. Considering the MTC component, 10/22 (45.4 %) patients did not show any somatic mutation, 7 of 22 (31.8 %) harbored the M918T RET somatic mutation and 4/22 (18.2 %) presented mutations in the H-RAS gene. In an additional case (1/22, 4.6 %), H-RAS and RET mutations were simultaneously present. Considering the PTC component, 1 of 24 (4.2 %) patients harbored the V600E BRAF mutation, 1 of 24 (4.2 %) the T58A H-RAS mutation and 1 of 24 (4.2 %) the M1T K-RAS mutation, while the remaining PTC cases did not show any somatic mutation. In one case, the MTC harbored a RET mutation and the PTC a BRAF mutation. None of the mutations found were present in both tumors. CONCLUSIONS: To our knowledge, this is the first study analyzing a possible involvement of RET, BRAF and RAS oncogene mutations in PTC/MTC. These data clearly suggest that the classical activating mutations of the oncogenes commonly involved in the pathogenesis of PTC and MTC may not be responsible for their simultaneous occurrence.

Radioiodine post-surgical remnant ablation in patients with differentiated thyroid cancer: news from the last 10 years.

Due to the growing incidence of differentiated thyroid carcinoma (DTC) and in particular of small papillary thyroid cancer observed in the last few decades, the indications, the activity of radioiodine (131I) to be administered, and the efficacy of post surgical thyroid 131I remnant ablation (RRA) have been widely discussed. In the last 10 years, the use of recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW) to stimulate the 131I remnant uptake has also interested many authors. The general agreement is that small (≤1 cm) intrathyroidal unifocal DTC with a favorable histology and no node metastases should not be submitted to RRA because of the low risk of relapse and cancer specific mortality. Conversely, RRA is indicated in patients with a higher risk level since it seems to reduce recurrence rates and mortality. The recent demonstration that the RRA preparation with rhTSH is as effective as THW using either high (100 mCi) or low (30 mCi) 131I activities suggests that rhTSH preparation and low activity of 131I should be considered as the standard of care for both low- and intermediate-risk DTC patients in the near future. Moreover, the use of low 131I activities and rhTSH reduces whole body radiation exposure and improves the quality of life which are very important advantages for DTC patients.