Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

/pdf/european-position-paper-on-rhinosinusitis-and-nasal-polyps-mj734vsl7p.pdf

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

Autophagy is a highly conserved catabolic process induced under various conditions of cellular stress, which prevents cell damage and promotes survival in the event of energy or nutrient shortage and responds to various cytotoxic insults. Thus, autophagy has primarily cytoprotective functions and needs to be tightly regulated to respond correctly to the different stimuli that cells experience, thereby conferring adaptation to the ever-changing environment. It is now apparent that autophagy is deregulated in the context of various human pathologies, including cancer and neurodegeneration, and its modulation has considerable potential as a therapeutic approach.

Mechanism and medical implications of mammalian autophagy

Objective: The aim was to provide guidelines for evaluation, treatment, and genetic testing for multiple endocrine neoplasia type 1 (MEN1). Participants: The group, which comprised 10 experts, including physicians, surgeons, and geneticists from international centers, received no corporate funding or remuneration. Process: Guidelines were developed by reviews of peer-reviewed publications; a draft was prepared, reviewed, and rigorously revised at several stages; and agreed-upon revisions were incorporated. Conclusions: MEN1 is an autosomal dominant disorder that is due to mutations in the tumor suppressor gene MEN1, which encodes a 610-amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. MEN1 is characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. Some patients may also develo...

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Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1)

Background: Prophylactic central neck dissection (CND) has been proposed in the treatment of patients affected by papillary thyroid carcinoma (PTC) with clinically negative neck lymph nodes The procedure allows pathologic staging of lymph nodes of the central compartment and treatment of the micrometastases Nevertheless, the morbidity that its routine use adds to the total thyroidectomy must be taken into account The aim of this study was to characterize the morbidity that CND adds to the total thyroidectomy Methods: This was a retrospective study of 1087 patients with PTC and clinically negative neck lymph nodes Patients were divided into three study groups: Group A, total thyroidectomy; Group B, total thyroidectomy and ipsilateral CND; Group C, total thyroidectomy and bilateral CND Primary endpoints of the study were evaluated by comparing the rates of transient and permanent recurrent laryngeal nerve (RLN) injury and hypoparathyroidism in the three study groups Results: Analysis of data showed n

Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature.

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.

Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy.

Clin. Otolaryngol. 2010, 35, 118–124



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.

Treatment and prognostic factors of papillary thyroid microcarcinoma.

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.

Nasal polyposis in Churg-Strauss syndrome.

Rhabdomyosarcoma and Ewing's sarcoma are relatively common malignant tumours in paediatric population. In the past, surgery was the mainstay of treatment and survival rates were poor. Afterwards, the development of multi-agent chemotherapy protocols during the past four decades resulted in a dramatic improvement in long-term survival. As a consequence, the significance of surgery has been the subject of critical discussion in the literature. Nowadays the standard treatment of rhabdomyosarcoma and Ewing's sarcoma consists in a multimodal therapy involving chemotherapy, radiotherapy and surgery. Nevertheless, the role of surgery still remains controversial. In particular, the cure of head and neck localizations presents debatable aspects since defined criteria to establish the risks and the benefits of surgical treatment do not exist at this time. This article reviews the role of surgery in children with head and neck rhabdomyosarcoma and Ewing's sarcoma. Indications, feasibility and timing criteria of surgical treatment have been reviewed and extracted from literature. Our case series is also presented.

Davide Giordano

Papers

Complications of central neck dissection in patients with papillary thyroid carcinoma: results of a study on 1087 patients and review of the literature.

Cadherin-6 promotes EMT and cancer metastasis by restraining autophagy.

Treatment and prognostic factors of papillary thyroid microcarcinoma.

Nasal polyposis in Churg-Strauss syndrome.

The role of surgery in children with head and neck rhabdomyosarcoma and Ewing's sarcoma