Notch pathway is activated by MAPK signaling and influences papillary thyroid cancer proliferation.

Mutually exclusive genetic alterations in the RET, RAS, or BRAF genes, which result in constitutively active mitogen-activated protein kinase (MAPK) signaling, are present in about 70% of papillary thyroid carcinomas (PTCs). However, the effect of MAPK activation on other signaling pathways involved in oncogenic transformation, such as Notch, remains unclear. In this study, we tested the hypothesis that the MAPK pathway regulates Notch signaling and that Notch signaling plays a role in PTC cell proliferation. Conditional induction of MAPK signaling oncogenes RET/PTC3 or BRAF(T1799A) in normal rat thyroid cell line mediated activation of Notch signaling, upregulating Notch1 receptor and Hes1, the downstream effector of Notch pathway. Conversely, pharmacological inhibition of MAPK reduced Notch signaling in PTC cell. Thyroid tumor samples from transgenic mice expressing BRAF(T1799A) and primary human PTC samples showed high levels of Notch1 expression. Down-regulation of Notch signaling by γ-secretase inhibitor (GSI) or NOTCH1 RNA interference reduces PTC cell proliferation. Moreover, the combination of GSI with a MAPK inhibitor enhanced the growth suppression in PTC cells. This study revealed that RET/PTC and BRAF(T1799A) activate Notch signaling and promote tumor growth in thyroid follicular cell. Taken together, these data suggest that Notch signaling may be explored as an adjuvant therapy for thyroid papillary cancer.

Classification of papillary thyroid microcarcinoma according to size and fine-needle aspiration cytology: Behavior and therapeutic implications.

BACKGROUND: The purpose of this study was to assess and classify cases of papillary microcarcinoma according to size (up to 0.5 cm and between 0.6 and 1.0 cm) and fine-needle aspiration cytology (FNAC). These results were then correlated with clinical and histopathologic factors of worse prognosis. METHODS: A total of 448 cases of papillary thyroid carcinoma were studied retrospectively. RESULTS: Of the 448 patients, 173 presented with carcinomas of ≤0.5 cm and 275 patients presented with carcinomas sized between 0.6 and 1.0 cm (>0.5 cm). Lymph node metastasis was diagnosed in 6% of the carcinoma cases of ≤0.5 cm and in 16% of the cases with tumors of >0.5 cm. A total of 281 cases tested positive for papillary carcinoma by FNAC, and in 113 cases, the carcinoma was diagnosed during the histopathologic examination. A positive FNAC for carcinoma was correlated with a higher incidence of lymph node metastasis (16% vs 5%). CONCLUSION: The diagnosis of papillary carcinoma using the preoperative biopsy enables a more precise oncological procedure with greater chance of biological cure.

Análise retrospectiva das tireoidectomias realizadas por residentes de cirurgia geral em hospital universitário / Retrospective analysis of the thyroidectomies performed by general surgery resident in a university hospital

Introdução: Com o objetivo de avaliar as complicações das tireoidectomias realizadas no Hospital Geral do Grajaú, da Faculdade de Medicina da UNISA, durante o período de novembro de 2000 a agosto de 2003, foram analisados retrospectivamente 105 prontuários. Métodos: Todas as cirurgias foram realizadas pelo residente do segundo ano de Cirurgia Geral sob a supervisão de um especialista. Os pacientes foram analisados de acordo com o gênero, idade, duração média da cirurgia, tempo de internação pós-operatório e complicações apresentadas. Resultados: Na série estudada, 85,7% dos pacientes (90 casos), era do gênero feminino. A idade média dos pacientes foi de 50,5 anos, tendo um predomínio de doenças benignas (84% dos casos). A tireoidectomia total foi realizada em 77,1% dos pacientes (81 casos) e 96% dos pacientes receberam alta em até 48 horas após a cirurgia. As complicações encontradas foram: hipocalcemia definitiva em 0,95% (um caso); paralisia transitória do nervo laríngeo recorrente em 2,85% (três casos) e definitiva em 1,9% (dois casos); hematoma com posterior necessidade de reabordagem em 1,9% (dois casos) e desenvolvimento de hipotireoidismo em 50% dos casos que foram submetidos à tireoidectomia não total e nenhum óbito. Conclusão: A tireoidectomia é um procedimento com baixa morbimortalidade, sendo segura, mesmo quando realizado por cirurgiões em treinamento, desde que sob a supervisão direta de um especialista.

Introduction: In order to evaluate the thyroidectomies done in Grajaú General Hospital - UNISA - Medical University from November, 2000 to August, 2003, 105 patients were retrospectively analyzed. Methods: All surgeries were performed by the general surgery 2nd year resident under a specialist supervision. The patients were analyzed according to the gender, age, average duration of the surgery, postoperative permanence into the hospital, and diagnosed complication. Results: In the analyzed series, 85.7% of the patients (90 cases), were women. The age average was 50.5 years-old with a predominance of benign pathology (84.4% of the cases). The total thyroidectomy was performed in 77.1% (81 cases) and 96% of the patients were discharged from hospital in 48 hours after surgery. The following complications were found: definitive hypocalcemia in 0.95% (1 case); transitory palsy of the laryngeal nerve in 2.85% (3 cases); definitive palsy of the laryngeal nerve in 1.9% (2 cases); hematoma with posterior need of reoperation in 1.9% (2 cases); development of hypothyroidism in 50% of the cases which underwent to non total thyroidectomy. There was no death. Conclusion: The thyroidectomy is a low morbimotality procedure and it is safe, even when performed by surgeons in training, since under straight specialist supervision.