Beatriz G. Cavalheiro

Negative and positive predictive values of nerve monitoring in thyroidectomy.

Recurrent nerve injury is 1 of the most important complications of thyroidectomy. During the last decade, nerve monitoring has gained increasing acceptance in several centers as a method to predict and to document nerve function at the end of the operation. We evaluated the efficacy of a nerve monitoring system in a series of patients who underwent thyroidectomy and critically analyzed the negative predictive value (NPV) and positive predictive value (PPV) of the method.

Expression of Matrix Metalloproteinase 2 (MMP-2) and Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) in Medullary Thyroid Carcinoma: Prognostic Implications

BACKGROUND Metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) participate in the degeneration of the extracellular matrix and are associated with carcinogenesis. MMP-2 is one of the main metalloproteinases active in neoplasia and is a marker of the malignant phenotype. Since the biological behavior of medullary thyroid carcinoma (MTC) varies widely, the present study was undertaken to determine if there is a correlation between the clinical evolution of MTC and the immunohistochemically detected expression of these enzymes in thyroid surgical specimens containing MTC. If so, their expression would be a novel indicator of the prognosis of MTC. METHODS Thirty-seven patients with MTC who had undergone thyroid surgery were followed for an average of 73 months. Immunohistochemical staining for metalloproteinase-related enzymes was performed in surgical paraffin blocks. The clinical status of the patients after surgery and at the end of the study period was characterized to determine correlations between these and the immunohistochemical markers. A value of p < 0.05 was considered statistically significant. RESULTS At the end of the study period, 15 patients (40.5%) were alive and without evidence of MTC, 17 (45.9%) had persistent MTC, and 5 (13.5%) had a relapse of their neoplasia. Four patients (10.8%) died during the course of the study. There was a significant correlation (p = 0.0005) between the immunohistochemical staining for MMP-2 and the clinical condition of the patients at the end of the study period, and a correlation between the state of apparent cure compared to persistence of MTC after thyroid surgery (p = 0.0207). No significant correlations were observed between either TIMP-2 expression or immune marking of metastatic lymph nodes and the clinical variables studied. CONCLUSION Immunohistochemical expression of MMP-2 in thyroid surgical specimens from patients with MTC is a novel indicator of the prognosis of this cancer.

Prognostic influence of clinical and pathological factors in medullary thyroid carcinoma: a study of 53 cases

OBJECTIVES AND INTRODUCTION Medullary thyroid carcinoma, a neoplasia of intermediate prognosis and differentiation, does not always respond predictably to known treatments. This study aimed to correlate the clinical progression of surgically treated patients with clinical and pathological data. METHODS A total of 53 patients were followed for 75 months (mean average) in tertiary-care hospital. The clinical status of patients at the end of the study period was characterized to determine correlations with a range of disease aspects. A value of p < 0.05 was considered statistically significant. RESULTS Twenty-two patients (41.5%) were alive and disease-free at the end of the follow-up period; twenty-three patients (43.4%) had persistent disease; and eight patients (15.1%) had recurrent disease. Four patients (7.6%) died from medullary thyroid carcinoma with clinical and/or imaging evidence of neoplasia. The following aspects demonstrated statistically significant correlations with the final medical condition: positive initial cervical examination (p = 0.002); neoplastic extensions to the thyroid capsule (p = 0.004) and adjacent tissues (p = 0.034); cervical lymph node metastases (p < 0.001); diameter of neoplasia (p = 0.018); TNM (tumor, node and metastasis) Stage (p = 0.001) and evidence of distant and/or cervical diseases in the absence of a cure (p = 0.011). Through logistic regression, the presence of cervical lymph node metastases was considered an independent variable (p < 0.001). CONCLUSIONS Clinical and pathological aspects of patients with surgically treated medullary thyroid carcinomas are predictors of disease progression. Specifically, even treated cervical lymph node metastases are significantly correlated with disease progression.

Expression of membrane type 1 matrix metalloproteinase in medullary thyroid carcinoma: prognostic implications.

Clinical and pathologic examinations cannot always provide a prognosis for patients with medullary thyroid carcinoma. Membrane type 1 matrix metalloproteinase (MT1‐MMP) can act directly on carcinogenesis and takes part in 1 of the processes of metalloproteinase 2 activation, an enzyme related to prognostic impairment of patients with such tumor.

Deaths related to differentiated thyroid cancer: a rare but real event

Objective The present study describes the clinical and tumor characteristics of patients that died from differentiated thyroid cancer and reports on the cause and circumstances of death in these cases. Subjects and methods Retrospective analysis of all the differentiated thyroid cancer (DTC) related deaths at a single institution over a 5-year period, with a total of 33 patients. Results Most of the patients were female (63.6%), with a mean age at diagnosis of 58.2 years. The most common histologic type was papillary (66.7%) and 30.3% were follicular. The distribution according to the TNM classification was: 15.4% of T1; 7.7% T2; 38.4% T3; 19.2% of T4a and 19.2% of T4b. Forty-four percent of cases were N0; 20% N1a and 36.6% of N1b. Twelve patients were considered non-responsive to radioiodine. Only one of the patients did not have distant metastases. The most common metastatic site was the lung in 69.7%. The majority of deaths were due to pulmonary complications related to lung metastases (17 patients, 51.5%), followed by post-operative complications in 5 cases, neurological disease progression in 3 cases, local invasion and airway obstruction in one patient. Median survival between diagnosis and death was reached in 49 months while between disease progression and death it was at 22 months. Conclusion Mortality from DTC is extremely rare but persists, and the main causes of death derive from distant metastasis, especially respiratory failure due to lung metastasis. Once disease progression is established, median survival was only 22 months.

Ratio of Metalloproteinase 2 to Tissue Inhibitor of Metalloproteinase 2 in Medullary Thyroid Carcinoma

OBJECTIVES To develop an index for the ratio of metalloproteinase 2 (MMP-2) to its tissue inhibitor (TIMP-2) in immunostained medullary thyroid carcinoma specimens and to correlate it with clinical and pathologic prognostic factors. Metalloproteinases, enzymes related to the degradation of the extracellular matrix, take part in carcinogenesis and have been associated with the prognosis of neoplasias. Nevertheless, medullary carcinoma is rarely considered in research analysis. Researchers tend to favor the ratio of enzymes to their inhibitors over the absolute concentrations of these enzymes. DESIGN Retrospective study of surgical samples. SETTING Head and Neck Surgery and Endocrinology Departments, Universidade de São Paulo Medical School Hospital. PATIENTS Surgical specimens from 33 patients who had been observed for a mean of 76.8 months (range, 4-201 months) were immunohistochemically stained for MMP-2 and TIMP-2. Only patients whose clinical and pathologic data were complete and whose specimens were preserved were included in the study. MAIN OUTCOME MEASURES The ratio between the expressions of MMP-2 and TIMP-2 was based on a staining index (immunostaining extent and intensity) of each of the markers. RESULTS Proportionally large expressions of TIMP-2 over MMP-2 correlated with low occurrences of positive findings on initial cervical examination for the presence of thyroid nodules and/or lymphadenopathy (P = .02) and cervical lymph node metastases (P < .001), conditions correlated with prognosis. A correlation with cure at the end of follow-up (P = .01) was also observed. (P< .05 was considered statistically significant.) CONCLUSION The ratio of MMP-2 to TIMP-2 expression is an additional and novel prognostic predictor of the outcome of medullary carcinoma treated surgically.

Malignancy Rates in Thyroid Nodules Classified as Bethesda Categories III and IV: Retrospective Data from a Tertiary Center

Background Thyroid fine needle aspiration (FNA) has a well-established role in the diagnosis of thyroid nodules, and the “Bethesda system for reporting thyroid cytopathology” is used to interpret FNA results. Bethesda categories III and IV encompass varying risks of malignancy. In addition, there is some debate in the literature about how to select among many acceptable treatment approaches. Objectives To establish an association between these 2 cytological categories and malignancy rates in patients treated in a referral tertiary cancer center, where surgical treatment is recommended for all these patients. Methods A total of 615 thyroid nodules (582 patients) were included in this retrospective study. There were 478 nodules that were classified as Bethesda category III and 137 nodules as Bethesda category IV. Electronic records were reviewed to establish a correlation between the FNA cytological results and the final histopathological analyses. Incidentally detected carcinomas were considered separately. Results Among the bethesda category III group, 75 malignant nodules (15.7%) were coincident with the target nodule (74 patients, 16.2%). Incidental carcinomas were found in 13.8% of these patients. The remaining 403 (84.3%) target nodules were benign. Among the bethesda category IV nodules, 23 malignant nodules (16.8%) were coincident with the target nodule. Incidental carcinomas were found in 25 patients (19.7%). The other 114 target nodules were benign. A total of 46 patients (52.3%) had carcinomas in the thyroid lobe contralateral to the one containing the target nodule, and 40 patients (45.5%) had carcinomas exclusively in the contralateral lobe. Conclusions We observed a 16% rate of malignancy in nodules classified as bethesda category III and 17% among bethesda category IV. When incidental carcinomas were included, the rates of malignancy doubled.

DEATH RELATED TO PULMONARY METASTASIS IN PATIENTS WITH DIFFERENTIATED THYROID CANCER

OBJECTIVE The purpose of the present study was to investigate the predictive factors for shorter disease-specific survival in patients with pulmonary disease secondary to differentiated thyroid cancer (DTC). METHODS This was a retrospective cohort study conducted over a 5-year period that included 54 patients with pulmonary disease secondary to DTC during the follow-up. Among these patients, 13 (24.1%) died from the disease. Dedifferentiation characteristics were identified at pathological examination of the metastatic disease (lymph node or distant metastases) and was defined as the abrupt transformation of a well-differentiated tumor into high-grade morphology lacking the original distinct histologic characteristics. RESULTS Tumor dedifferentiation marked by cellular aberrations and radioiodine (RAI) therapy resistance occurred in 5 (9.3%) patients. Four of them died due to pulmonary progression (80.0%), and the median survival of this group was 30 months compared to 279 months in the patients without dedifferentiation. The cumulative disease-specific survival was 20.0% in the patients with dedifferentiation during the follow-up versus 46.1% among the cases without this condition (P = .003, log-rank test). Moreover, dedifferentiation was independently associated with shorter disease-specific survival (hazard ratio [HR] = 31.607; 95% confidence interval [CI]: 4.815-207.478; P<.0001, Cox regression model) as were age over 45 years (HR = 10.904; 95% CI: 1.145-103.853; P = .038) and male sex (HR = 4.210; 95% CI: 1.056-16.783; P = .042). CONCLUSION DTC patients with pulmonary disease exhibited shorter disease-specific survival, particularly those who developed tumor dedifferentiation, and these patients require special attention during follow-up. ABBREVIATIONS CI = confidence interval DTC = differentiated thyroid cancer FTC = follicular thyroid carcinoma HR = hazard ratio IQR = interquartile range LN = lymph node LR = likelihood ratio PTC = papillary thyroid carcinoma RAI = radioiodine pTNM = pathologic tumor-node-metastasis stage system.

Multifocal myositis ossoficans in masticatory muscles 30 years after gunshot wound: case report and literature review.

A miosite ossificante é uma condição benigna, não neoplásica, caracterizada pela formação óssea heterotópica nos músculos e em outros tecidos moles, frequentemente associada a traumas diretos e agudos.1 Geralmente ocorre como lesão única nas extremidades, principalmente nas extremidades inferiores, mais suscetíveis a traumas. Nos últimos 50 anos, foram relatadas poucas dezenas de casos em musculatura de face e seu diagnóstico diferencial faz-se com condições malignas, especialmente quando não se identifica trauma associado.

Surgical treatment for thyroid carcinoma: retrospective study with 811 patients in a Brazilian tertiary hospital

Objective The aim of the present study was to describe the epidemiologic data, histological type, treatment and follow-up of the 811 patients treated for thyroid cancer in Instituto do Câncer do Estado de São Paulo (ICESP) over 5 years. Materials and methods Retrospective analyses of electronic chart information. Results There were 679 cases (83.7%) of papillary thyroid cancer, 61 (7.5%) of follicular carcinoma, 54 (6.7%) of medullary carcinoma, 11 (1.4%) of poorly differentiated carcinoma and 6 of anaplastic carcinoma (0.7%). The majority of patients were female (82.2%), and the mean age was 50.5 ± 15 years. Two hundred forty-two patients had disease persistence or recurrence. At the last follow-up, 629 (77.6%) patients were alive and disease free, 141 (17.4%) were alive with disease, and 41 (5.1%) were deceased, with 37 deaths related to thyroid cancer. Conclusion This study was able to outline the profile, disease type and evolution of patients treated for thyroid cancer at a single tertiary hospital.