Massimo De Falco

Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth.

Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.

Prevalence, diagnosis and management of ectopic thyroid glands

Ectopic thyroid tissue (ETT) is an uncommon entity that may be found anywhere along the line of the obliterated thyroglossal duct, usually from the tongue to the diaphragm. We performed a retrospective analysis of patients undergoing surgical treatment for thyroid disease between January 2000 and December 2013, seeking for ETT All patients with prior neck surgery or trauma were excluded. The clinic-pathologic features, prevalence and diagnosis of the lesions were collected and analyzed. Out of 3092 included patients, 28 ETT were identified (0.9%). The anatomical site of ETT was as follows: lateral cervical in 6 (21.4%), along the thyroglossal duct in 6 (21.4%), mediastinal in 5 (17.9%), lingual in 5 (17.9%), sublingual in 3 (10.7%), and submandibular in 3 (10.7%). Histopathology revealed 27 benign lesions and 1 (3.6%) papillary carcinoma. ETT is found in less than 1% of patients receiving thyroid surgery. Diagnosis of ETT requires clinical imaging. Surgery is a prudent choice due to the potential of malignant evolution of ETT.

Double probe intraoperative neuromonitoring with a standardized method in thyroid surgery

INTRODUCTION The purpose of this study was to evaluate the effectiveness of intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) and the vagus nerve (VN) with a standardized approach in thyroid surgery. METHODS Retrospective study with an experimental group with which IONM was used, both with the RLN that the VN, and a control one, each consisting of 300 total thyroidectomies. Each patient underwent a pre-and post-operative videolaryngoscopy. The number of RLNs identified and the number of transient and permanent RNL injuries for each group were assessed, and then compared with χ(2) tests. In the experimental group Sensitivity, Specificity, Positive Predictability, Negative Predictability and Accuracy of IONM were evaluated, depending on the number of true positive results, false negatives, true negatives and false positives obtained by comparing the results of IONM with the post-operative videolaryngoscopies. RESULTS The results obtained for the experimental group vs. the control group were: RLNs identified 595 (99.1%) vs. 552 (92%) -P Value <0.0001; Permanent RLNs injuries 4 (1.33%) vs. 5 (1.67%) -P Value 1; transient RLNs injuries 1 (0.33%) vs. 8 (2.67%) -P Value 0.044. The IONM system, for the RLN and VN showed respectively: Sensitivity 66.7% vs. 83.3%; specificity 97.6% vs. 99.5%; Positive Predictability 22.2% vs. 62.5%; Negative Predictability 99.6% vs. 99.3%; Accuracy 97.3% vs. 99.3%. CONCLUSIONS Our study highlights that using IONM with a standardized method in thyroid surgery, improves the ability to identify the RLN and a reduction in the incidence rate of transient RLN injuries.

Cancer of the thyroid gland in geriatric age: A single center retrospective study with a 10-year post-operative follow-up

INTRODUCTION We evaluated the characteristics of thyroid carcinoma in geriatric patients and outcomes after a 10-years follow-up. METHODS Comparative retrospective study on a group of 31 geriatric patients and one of 224 non-geriatric, who underwent surgery for thyroid carcinoma in the period 1998-2003. We compared with Fishers exact test: histology, multifocality, tumor size, lymph-node metastasis, distant metastasis, persistence/recurrence and mortality, including and excluding anaplastic carcinomas, in a subgroup of 26 geriatric patients and another of 223 non-geriatric patients. RESULTS RESULTS for the geriatric and non-geriatric groups and in the geriatric and non-geriatric subgroups respectively were as follows: multifocality 9/31 vs. 74/224 (p-value 0.8382) and 9/26 vs. 74/223 (p-value 1); tumor size: 16/31 vs. 28/224 T3-T4 (p-value < 0.0001) and 11/26 vs. 27/223 T3-T4 (p-value 0.0004); lymph-node metastases: 17/31 vs. 34/224 (p-value < 0.0001) and 12/26 vs. 33/223 (p-value 0.0004); distant metastases: 8/31 vs. 3/224 (p-value < 0.0001) and 3/26 vs. 2/223 (p-value 0.0088); disease recurrence/persistence: 11/31 vs. 3/224 (p-value < 0.0001) and 6/26 vs. 2/223 (p-value > 0.0001); mortality: 7/31 vs. 2/224 (p-value < 0.0001) and 2/26 vs. 1/223 (p-value 0.0295). Anaplastic carcinomas were predominantly in the geriatric group: 5 vs. 1 (p-value < 0.0001). No statistical differences for other histotypes. DISCUSSION Thyroid carcinoma is more aggressive in geriatric patients. This may justify a more aggressive surgical strategy with possible prophylactic lymphadenectomy, in addition to ablative therapy with (131)I and suppressive therapy with levothyroxine. CONCLUSION It would be useful to undertake randomized prospective studies on a large cohort of patients to determine the most effective therapy for geriatric patients suffering from thyroid carcinoma.

Thyroid and Parathyroid Diseases in Elderly Patients

Goiter size is likely to be larger in geriatric patients than in young people. If a hypothyroidism is recognized, symptoms can be characterized by bodyweight gain, asthenia and fatigue, hypersomnia, heat intolerance, myxedema, constipation, skin and appendages disorders, psychiatric depression, altered consciousness or impaired concentration ability and heart failure; in cases of regular functions, symptoms may only be mechanical, such as dyspnea, dysphagia and rarely dysphonia. To assess the thyroid function, the dosage of TSH, FT3 and FT4 is necessary together with the measurement of Ab-hTg and Ab-TPO. Instrumental diagnosis consists firstly of an US-scan; chest and thorax CT scan are required in cases of sub sternal widening. The diagnostic has to be completed by performing a needle biopsy, in cases of solid lumps with suspicious characteristics.