The increased rates of transient and permanent hypoparathyroidism in our series suggest a critical review of indications for the routine use of prophylactic CND for PTC. Prophylactic CND ipsilateral to the tumor associated with total thyroidectomy may represent an effective strategy for reducing the rate of permanent hypoparathyroidism. Concomitant completion contralateral paratracheal lymph node neck dissection should be performed in presence of lymph node metastasis on intraoperative frozen-section pathology. This approach limits the use of bilateral CND to patients with intraoperative pathological findings of lymph node metastases.
The transdifferentiation of epithelial cells toward a mesenchymal condition (EMT) is a complex process that allows tumor cells to migrate to ectopic sites. Cadherins are not just structural proteins, but they act as sensors of the surrounding microenvironment and as signaling centers for cellular pathways. However, the molecular mechanisms underlying these signaling functions remain poorly characterized. Cadherin-6 (CDH6) is a type 2 cadherin, which drives EMT during embryonic development and it is aberrantly re-activated in cancer. We recently showed that CDH6 is a TGFβ target and an EMT marker in thyroid cancer, suggesting a role for this protein in the progression of this type of tumor. Papillary thyroid carcinomas (PTCs) are usually indolent lesions. However, metastatic spreading occurs in about 5% of the cases. The identification of molecular markers that could early predict the metastatic potential of these lesions would be strategic to design more tailored approaches and reduce patients overtreatment. In this work, we assessed the role of CDH6 in the metastatic progression of thyroid cancer. We showed that loss of CDH6 expression profoundly changes cellular architecture, alters the inter-cellular interaction modalities and attenuates EMT features in thyroid cancer cells. Using a yeast two-hybrid screening approach, based on a thyroid cancer patients library, we showed that CDH6 directly interacts with GABARAP, BNIP3 and BNIP3L, and that through these interactions CDH6 restrains autophagy and promotes re-organization of mitochondrial network through a DRP1-mediated mechanism. Analysis of the LIR domains suggests that the interaction with the autophagic machinery may be a common feature of many cadherin family members. Finally, the analysis of CDH6 expression in a unique cohort of human PTCs showed that CDH6 expression marks specifically EMT cells. and it is strongly associated with metastatic behavior and worse outcome of PTCs.
Objective: To discuss the prognostic factors and outcomes of treatment in patients diagnosed with papillary thyroid microcarcinoma. Design: Retrospective observational case review. Setting: Department of Otorhinolaryngology of the tertiary referral teaching hospital of Parma. Participants: Ninety-seven patients diagnosed with PTMC and surgically treated between January 1998 and December 2007. Main outcome measures: Clinical and histopathological characteristics of the study group were identified and statistically analysed. Results: No cancer-related deaths were registered. Incidence of recurrent disease was 9% after a 43 month mean follow-up (range 12-120). Univariate analysis detected that metastases in neck lymph nodes at diagnosis (p = 0.025), a tumour >5 mm in size (p = 0.011), the presence of bilateral tumoural foci (p = 0.007), the presence of capsular invasion (p = 0.001), and the presence of vascular invasion (p = 0.004) were related to recurrent disease. On multivariate analysis, the presence of bilateral tumoural foci (p = 0.030), and the presence of capsular invasion (p = 0.005) were significantly related to tumour recurrence. Conclusion:The prognosis for patients with papillary thyroid microcarcinoma in this series was excellent, with a 100% survival rate and minimal surgical-related morbidity. Nevertheless, approximately 10% of patients developed recurrent disease; aggressive treatment may be justified depending on the presence or absence of prognostic risk factors.Papillary thyroid microcarcinoma (PTMC) is defined by the World Health Organisation as a papillary thyroid cancer measuring 10 mm or less in maximum diameter.
Objectives: Churg‐Strauss syndrome (CSS) is a systemic vasculitic disorder of unknown etiology that affects small‐to‐medium‐size blood vessels. Patients affected by CSS frequently show ear, nose, and throat manifestations, which are often present at the time of disease onset. The purpose of this study was to determine the frequency of nasal polyposis in a series of 29 patients with CSS and to correlate the nasal findings to the total health situation of these patients. Study Design: Retrospective analysis. Setting: Department of Otolaryngology and Department of Clinical Medicine, Nephrology and Health Science, University of Parma. Methods: Twenty‐nine patients with CSS were identified. Of the 29 patients, 17 (58.6%) had nasal polyposis and were enrolled in this study. The nasal polyps were graded according to the Lund and Mackay endoscopic and radiological classifications. Results: At diagnosis, endoscopic intranasal evaluation identified nasal polyposis of grade 3 in nine cases (52.9%), grade 2 in six cases (35.2%), and grade 1 in the remaining case (5.8%). After corticosteroid and immunosuppressive therapy, clinical remission was achieved in 14 patients (82.3%), whereas 3 patients experienced a relapse. Posttreatment endoscopic evaluation showed a permanent disappearance (grade 0) of nasal polyps in eight patients (47%). The other nine patients (52.92%) were found to have a small polyp situated in the middle meatus (grade 1). Conclusions: Nasal polyposis in patients with CSS may represent the initial phase of the syndrome, though patients often have concurrent pulmonary disease. Corticosteroid therapy either alone or combined with immunosuppressive drugs usually yielded improvement or stabilization.
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