Active Surveillance of Thyroid Microcarcinomas: a Critical View.

PURPOSE OF THE REVIEW: There has been an increasing interest on active surveillance for papillary thyroid microcarcinomas (PTMC) in the literature. We will analyze the contributions of those authors who support this approach in most patients with low-risk tumors. RECENT FINDINGS: The development of molecular methods to effectively detect aggressive PTMC at the fine-needle aspiration biopsy will enable the sound indication of immediate surgery in those patients, assuring the other individuals with the far more frequent indolent PTMC will undergo active surveillance with less anxiety. Several studies compared the quality of life between patients with PTMC who underwent active surveillance with immediate total thyroidectomy. However, thyroid lobectomy is a quite acceptable intermediate alternative for most patients with PTMC, with less surgical morbidity. It is important to wait for worldwide validation, with reports from low- and middle-income areas, before recommending the routine adoption of active surveillance for patients with PTMC, due to difficult logistic obstacles in those environments.

Aderência intertalâmica e Alzheimer: estudo preliminar / Interthalamic adhesion and Alzheimer's: preliminary study

Objetivo: Descrever dimensões e prevalência da Aderência Intertalâmica (AI) em cadáveres do Serviço de Verificação de Óbitos da Capital - USP, considerando idade, sexo, peso, altura e histórico pessoal de doença de Alzheimer (DA). Métodos: Cinquenta e sete cadáveres (31H/26M) foram incluídos no estudo, com média de idade de 66,2 anos (variando entre 15 e 91 anos). A análise da AI foi feita após secção transversal da calota craniana e incisão axial no limite inferior do tronco encefálico seguida de retirada do encéfalo de sua cavidade. Cinquenta e quatro encéfalos foram submetidos a incisão sagital mediana, dois encéfalos foram submetidos a cortes axiais, e um encéfalo a secção coronal. Dados quantitativos foram comparadas pelo teste t de student, e dados qualitativos pelo teste de Qui Quadrado. A análise idade vs área foi feita por regressão linear. Resultados: A prevalência de AI foi de 79%, não havendo diferença significativa entre os sexos (p=0,68).  Observou-se associação entre menores áreas de secção sagital e idades mais avançadas (p=0,02). Não houve diferença significativa na prevalência de AI nem na área de secção transversal em pacientes com DA. Discussão: Ao contrário de estudos prévios, que associaram maior prevalência e tamanho de AI com sexo feminino, isso não foi observado em nossa casuística. Apesar de não ser estatisticamente significativa nota-se uma diferença importante nas áreas médias de secção sagital dos grupos com e sem DA, o que aponta para a necessidade de estudos subsequentes com amostras maiores

Objective: Identifying the prevalence and dimensions of the Interthalamic Adhesion (ITA) in corpses from the "Serviço de Verificação de Óbitos da Capital - USP", considering factors as age, sex, weight, height, and diagnosis of Alzheimer's disease (AD). Methods: Fifty-seven corpses (31M/26F) were included in the study. The mean age was 66.2 (varying between 15 and 91). The analysis of the ITA was made after the encephalon's removal from its cavity, which occurred by the transversal section of the skullcap, and, next, an axial incision in the inferior limit of the pons to separate the encephalon from the spinal cord. Fifty-four encephalons were submitted to medial sagittal incisions, two encephalons were submitted to axial cuts and one to a coronal section. Quantitative data were compared by the Student's T Test, and qualitative data by the Chi-squared test. The Age vs Area analysis was made by linear regression. Results: the prevalence of the ITA was 79%, not having differences in prevalence between sexes (p=0.68). Advanced ages presented lower areas in sagittal sections (p= 0.02). It does not appear to have a significant alteration in prevalence of the ITA and transversal section aerea in patients with AD. Discussion: Unlike previous studies which observed higher prevalence and size of the ITA in females, differences in this parameters were not obtained in this study. Evidence of correlation between AD and lower sagittal section of the ITA, even without statistic significance, points to the need of further studies.

Abdominal compression: a new intraoperative maneuver to detect chyle fistulas during left neck dissections that include level IV.

BACKGROUND: Chyle fistulas may occur after left neck dissections that include level IV, due to injury of the thoracic duct or of 1 of its major branches. Despite being unusual, this complication carries substantial postoperative morbidity and even mortality. So far, no effective intraoperative maneuver has been reported to detect this fistula at the end of a neck dissection. In this cohort study, we sought to describe a simple new maneuver, intraoperative abdominal compression, which can effectively help to identify an open major lymphatic duct on level IV at the end of a neck dissection. PATIENTS AND METHODS: From March 1989 to September 2010, 206 patients underwent neck dissections involving left level IV, and underwent intraoperative abdominal compression. There were 119 men and 87 women, with ages ranging from 18 to 81 years (median, 52 years). One hundred forty-four patients had squamous cell carcinomas, 54 had thyroid carcinomas, 5 had malignant melanomas, and 3 had salivary cancers. Distribution by type of left neck dissection was: selective including levels II, III, and IV (73 cases; 35.4%), selective including levels II, III, IV, and V (55 cases; 26.6%), selective including levels I, II, III, and IV (12 cases; 5.8%), modified radical (47 cases; 22.8%), and radical (19 cases; 9.2%). In all cases, at the end of the procedure, the endotracheal tube was temporarily disconnected from the ventilator. Keeping the dissected level IV area under clear visualization, an abdominal compression was performed. At this moment, any detected lymphatic leak was carefully clamped and tied with nonabsorbable sutures. After ventilating the patient, the intraoperative abdominal compression was repeated to reassure complete occlusion of the lymphatic vessel. RESULTS: In 13 cases (6.3%), a chyle leak was detected after performing the intraoperative abdominal compression. All leaks except for 2 were successfully controlled after 1 attempt. In these 2 patients, a patch of muscle and fat tissue was applied with fibrin glue on the top. In 1 of these patients, another chyle leak in a different location was detected only at the second intraoperative abdominal compression, and was also effectively closed. Postoperatively, there were 2 (1%) chyle fistulas, both among these 13 cases, and all were successfully managed with clinical measures only. No fistulas occurred among the remaining 193 patients in whom intraoperative abdominal compression did not demonstrate lymphatic leak. CONCLUSION: To our knowledge, this is the first description of a specific maneuver to actively detect a lymphatic fistula at the end of a left neck dissection involving level IV. In this study, intraoperative abdominal compression was able to detect an open lymphatic vessel in 6.3% of the cases, as well as to assure its effective sealing in the remaining 93.7% of the patients. Moreover, no life-threatening high-volume fistula was noted in this study.

Negative and positive predictive values of nerve monitoring in thyroidectomy.

BACKGROUND: 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. METHODS: NIM System efficacy was prospectively analyzed in 447 patients who underwent thyroidectomy between 2001 and 2008 (366 female/81 male; 420 white/47 nonwhite; 11 to 82 years of age; median, 43 years old). There were 421 total thyroidectomies and 26 partial thyroidectomies, leading to 868 nerves at risk. The gold standard to evaluate inferior laryngeal nerve function was early postoperative videolaryngoscopy, which was repeated after 4 to 6 months in all patients with abnormal endoscopic findings. RESULTS: At the early evaluation, 858 nerves (98.8%) presented normal videolaryngoscopic features after surgery. Ten paretic/paralyzed nerves (1.2%) were detected (2 unexpected unilateral paresis, 2 unexpected bilateral paresis, 1 unexpected unilateral paralysis, 1 unexpected bilateral paralyses, and 1 expected unilateral paralysis). At the late videolaryngoscopy, only 2 permanent nerve paralyses were noted (0.2%), with an ultimate result of 99.8% functioning nerves. Nerve monitoring showed absent or markedly reduced electrical activity at the end of the operations in 25/868 nerves (2.9%), including all 10 endoscopically compromised nerves, with 15 false-positive results. There were no false-negative results. Therefore, the PPV was 40.0%, and the NPV was 100%. CONCLUSIONS: In the present series, nerve monitoring had a very high PPV but a low NPV for the detection of recurrent nerve injury.

Development of a sensitive and specific quantitative reverse transcription-polymerase chain reaction assay for blood thyroglobulin messenger ribonucleic acid in the follow-up of patients with differentiated thyroid carcinoma.

CONTEXT: Serum thyroglobulin is a sensitive tumor marker in the follow-up of patients with differentiated thyroid carcinoma (DTC), but the presence of endogenous anti-thyroglobulin antibodies (TgAb) can interfere on its measurement. To prevent interference by TgAb, several investigators have tried to quantify blood mRNA Tg by real-time RT-PCR, but the results have been variable, not reporting a correlation between mRNA Tg and the presence of metastases. OBJECTIVE: The aim of the study was to evaluate the development of a sensitive and specific quantitative RT-PCR assay for blood mRNA Tg in the follow-up of patients with DTC. DESIGN AND PATIENTS: An assay employing primers located in a region not affected by alternative splicing or single nucleotide polymorphisms was developed to study 104 DTC patients (13 of 104 with positive TgAb). RESULTS: The assay is specific for thyroid tissue because we found mRNA Tg expression in normal thyroid tissue, but we did not find any mRNA Tg expression in any extrathyroidal tissues. Quantitative mRNA Tg levels were significantly different between patients "free of disease" (82 of 104) and those with metastases (22 of 104) (2.61 +/- 0.26 vs. 27.58 +/- 1.62 pg mRNA Tg/microg RNA) (P < 0.0001). A cutoff point of 5.51 was able to discriminate between the two groups. In addition, the measurement of mRNA Tg was not affected by the presence of TgAb. CONCLUSION: This new mRNA Tg quantification is a reliable method that allowed us to differentiate patients free of disease from those with metastases, and it could represent an appropriate molecular marker for the follow-up of patients with DTC, especially those with positive TgAb.

How to minimize complications in thyroid surgery?

BACKGROUND: In ancient times, operations on the thyroid gland caused unacceptable morbidity and mortality. Only after the landmark work of Kocher, the technical principles of thyroidectomy were solidly established, and are still valid nowadays. METHODS: Revision article on practical suggestions to decrease morbidity associated with thyroidectomy, as well as warning against common pitfalls that the surgeon may encounter. RESULTS: The following subjects are objectively addressed: how to manage upper airway obstruction, how to avoid non-esthetic scars and how to recognize the most prevalent anatomic variations concerning the recurrent nerve, the external branch of the superior laryngeal nerve and the parathyroid glands, in order to decrease operative morbidity. CONCLUSION: The Head and Neck Surgeon must be fully aware of the complex anatomy of the central visceral compartment of the neck, as well as must be prepared to handle some complications of thyroidectomy that can be life-threatening.

Recurrent laryngeal nerve: a plexus rather than a nerve?

OBJECTIVES: To analyze the frequency of extralaryngeal branching (ELB) of the recurrent laryngeal nerve (RLN) in a consecutive series of patients undergoing thyroidectomy by the same group of surgeons during an extended period and to compare our findings with the data available in the literature. DESIGN: Retrospective medical record study. SETTING: Academic research. PATIENTS: From March 1, 1983, to September 30, 2008, 2677 patients underwent thyroidectomy. Of these, 1638 patients had surgical information about at least 1 RLN. A total of 1081 patients underwent bilateral operations. During the last 5 years of the study, intraoperative laryngeal nerve monitoring was performed in selected patients using a commercially available system. MAIN OUTCOME MEASURES: Information was obtained regarding 2154 RLNs. RESULTS: A total of 1390 RLNs (64.53%) had ELB. Among 447 patients in whom intraoperative laryngeal nerve monitoring was used, the anterior branches usually exhibited more electrophysiologic activity. CONCLUSIONS: Extralaryngeal branching was found in 64.53% of RLNs in this case series. In recent patients with intraoperative laryngeal nerve monitoring, electrophysiologic activity was observed in the branches, particularly the anteriorly situated ones. Recognition of this frequent anatomical configuration and meticulous preservation of all branches are of paramount importance to decrease postoperative morbidity associated with thyroidectomy.

Down-regulation of NR4A1 in follicular thyroid carcinomas is restored following lithium treatment.

INTRODUCTION: The identification of follicular thyroid adenoma-associated transcripts will lead to a better understanding of the events involved in pathogenesis and progression of follicular tumours. Using Serial Analysis of Gene Expression, we identified five genes that are absent in a malignant follicular thyroid carcinoma (FTC) library, but expressed in follicular adenoma (FTA) and normal thyroid libraries. METHODS: NR4A1, one of the five genes, was validated in a set of 27 normal thyroid tissues, 10 FTAs and 14 FTCs and three thyroid carcinoma cell lines by real time PCR. NR4A1 can be transiently increased by a variety of stimuli, including lithium, which is used as adjuvant therapy of thyroid carcinoma with (131)I. We tested if lithium could restore NR4A1 expression. The expression of other genes potentially involved in the same signalling pathway was tested. To this end, lithium was used at different concentration (10 mm or 20 mm) and time (2 h and 24 h) and the level of expression was tested by quantitative PCR. We next tested if Lithium could affect cell growth and apoptosis. RESULTS: We observed that NR4A1 expression was under-expressed in most of the FTCs investigated, compared with expression in normal thyroid tissues and FTAs. We also found a positive correlation between NR4A1 and FOSB gene expression. Lithium induced NR4A1 and FOSB expression, reduced CCDN1 expression, inhibited cell growth and triggered apoptosis in a FTC cell line. CONCLUSIONS: NR4A1 is under-expressed in most of FTCs. The loss of expression of both NR4A1 and the Wnt pathway gene FOSB was correlated with malignancy. This is consistent with the hypothesis that its loss of expression is part of the transformation process of FTCs, either as a direct or indirect consequence of Wnt pathway alterations. Lithium restores NR4A1 expression, induces apoptosis and reduces cell growth. These findings may explain a possible molecular mechanism of lithium's therapeutic action.

Perineural invasion in aggressive skin carcinomas of the head and neck. Potentially dangerous but frequently overlooked.

INTRODUCTION: Perineural invasion is a well-recognized form of cancer dissemination. However, it has been reported only in few papers concerning cutaneous carcinomas (basal cell, BCC, and squamous cell, SCC). Moreover, the incidence is considered to be very low. Niazi and Lambert [Br J Plast Surg 1993;46:156-157] reported only 0.18% of perineural invasion among 3,355 BCCs. It is associated with high-risk subtypes, as morphea-like, as well as with an increased risk of local recurrence. No paper was found in the literature looking for perineural invasion in very aggressive skin cancers with skull base extension, with immunohistochemical analysis. METHODS: This is a retrospective review, including 35 very advanced skin carcinomas with skull base invasion (24 BCCs and 11 SCCs, operated on at a single institution from 1982 to 2000). Representative slides were immunohistochemically evaluated with antiprotein S-100, in order to enhance nerve fibers and to detect perineural invasion. The results were compared to 34 controls with tumors with a good outcome, treated in the same time frame at the same Institution. RESULTS: Twelve (50.0%) of the BCCs with skull base invasion had proven perineural invasion, as opposed to only 1 (4.6%) of the controls, and this difference was statistically significant (p < 0.001). Regarding SCCs, 7 aggressive tumors (63.6%) showed perineural invasion compared to only 1 (10.0%) of the controls, but this difference did not reach significance (p = 0.08), due to the small number of cases. CONCLUSIONS: In this series, it was demonstrated that immunohistochemically detected perineural invasion was very prevalent in advanced skin carcinomas. In addition, it was statistically associated with extremely aggressive BCCs with skull base invasion.

Gene expression profiling of papillary thyroid carcinoma identifies transcripts correlated with BRAF mutational status and lymph node metastasis.

PURPOSE: To identify papillary thyroid carcinoma (PTC)-associated transcripts, we compared the gene expression profiles of three Serial Analysis of Gene Expression libraries generated from thyroid tumors and a normal thyroid tissue. EXPERIMENTAL DESIGN: Selected transcripts were validated in a panel of 57 thyroid tumors using quantitative PCR (qPCR). An independent set of 71 paraffin-embedded sections was used for validation using immunohistochemical analysis. To determine if PTC-associated gene expression could predict lymph node involvement, a separate cohort of 130 primary PTC (54 metastatic and 76 nonmetastatic) was investigated. The BRAF(V600E) mutational status was compared with qPCR data to identify genes that might be regulated by abnormal BRAF/MEK/extracellular signal-regulated kinase signaling. RESULTS: We identified and validated new PTC-associated transcripts. Three genes (CST6, CXCL14, and DHRS3) are strongly associated with PTC. Immunohistochemical analysis of CXCL14 confirmed the qPCR data and showed protein expression in PTC epithelial cells. We also observed that CST6, CXCL14, DHRS3, and SPP1 were associated with PTC lymph node metastasis, with CST6, CXCL14, and SPP1 being positively correlated with metastasis and DHRS3 being negatively correlated. Finally, we found a strong correlation between CST6 and CXCL14 expression and BRAF(V600E) mutational status, suggesting that these genes may be induced subsequently to BRAF activation and therefore may be downstream in the BRAF/MEK/extracellular signal-regulated kinase signaling pathway. CONCLUSION: CST6, CXCL14, DHRS3, and SPP1 may play a role in PTC pathogenesis and progression and are possible molecular targets for PTC therapy.

[Diagnosis of metastases in patients with papillary thyroid cancer by the measurement of thyroglobulin in fine needle aspirate]. / Diagnóstico de metástases de carcinoma papilífero de tiróide através da dosagem de tiroglobulina no líquido obtido da lavagem da agulha utilizada na punção aspirativa.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.

Diagnóstico de metástases de carcinoma papilífero de tiróide através da dosagem de tiroglobulina no líquido obtido da lavagem da agulha utilizada na punção aspirativa / Diagnosis of metastases in patients with papillary thyroid cancer by the measurement of thyroglobulin in fine needle aspirate

Com a introdução da ultra-sonografia cervical (USC) no seguimento dos pacientes com carcinoma papilífero de tiróide (CPT), tornou-se freqüente o encontro de pequenos linfonodos (LNs) cervicais. Porém, apesar de a USC apresentar alta sensibilidade, o estudo citológico obtido por punção aspirativa (PAAF) e, nos últimos anos, a dosagem da tiroglobulina (Tg) no lavado da agulha da PAAF (Tg-PAAF) vêm assumindo papel importante no diagnóstico de LNs cervicais. O objetivo deste estudo é verificar a acurácia da combinação da USC, citologia e Tg-PAAF em LNs suspeitos. Estudamos 32 pacientes que apresentavam 44 LNs à USC, classificados como "inflamatórios" (19) ou "suspeitos" (25). Dos 25 LNs suspeitos, 15 apresentavam Tg-PAAF elevada (13 com citologia compatível com metástases e 2 com citologia não-diagnóstica). Esses 15 LNs (11 pacientes) foram confirmados como metástase de CP pelo exame histopatológico. Os 19 LNs "inflamatórios" e os 10/25 LNs "suspeitos" apresentaram citologia negativa e Tg-PAAF indetectável. Concluímos que a USC apresenta alta sensibilidade na detecção de linfonodos cervicais, porém citologia e dosagem de Tg-PAAF são fundamentais para o diagnóstico. A associação USC, citologia e Tg-PAAF pode ser considerada a abordagem mais sensível e específica na detecção de LNs metastáticos em pacientes com CPT.

The widespread use of neck ultrasonography (US) during the follow-up of patients with papillary thyroid carcinoma (PTC) has led to the discovery of small cervical lymph nodes (LN). Although US has a high sensitivity for diagnosing LN, fine needle aspiration biopsy (FNA) and measurement of thyroglobulin in fine needle aspirates (FNA-Tg) have proven to be invaluable tools. The aim of this study is to determine the sensitivity of the combined use of neck US, FNA biopsy and FNA-Tg for diagnosis of cervical lymph nodes. We have studied 32 patients with 44 LN detected by US, 19 classified as inflammatory and 25 as suspicious. 15 of those 25 suspicious LN had high FNA-Tg (13 of the 15 had positive cytology and 2 indeterminate). All of these 15 LN (11 patients) were proven to be PTC metastasis by histopathology. All 19 inflammatory LN and those 10/25 suspicious LN, had cytology negative for malignancy and undetectable FNA-Tg. We conclude that fine needle aspiration biopsy and FNA-Tg combined with neck US are essential for detecting positive cervical lymph nodes due to its high sensitivity and specificity and it should be considered the standard for investigating locally recurrent disease in patients with PTC.

First-bite syndrome after resection of the styloid process.

BACKGROUND: First-bite syndrome (FBS) may occur after operations on parapharyngeal space. The main symptom is excruciating pain only after the first one or two bites of meals. OBJECTIVE: The objective of this article is to report a case of FBS after resection of the styloid process (SP). CASE REPORT: This 51-year-old woman had a 4-month history of pain on her left neck. Computed tomography scan showed a left hypertrophic SP. A diagnosis of Eagle syndrome (ES) was then established. She underwent excision of the left SP through a lateral cervicotomy. Postoperative recovery was uneventful with pain relief. However, 2 months postoperatively, intense pain appeared related to the first bite in every meal. She received 800 mg carbamazepine per day with good pain control. Medication was discontinued after 2 years with no further relapse. CONCLUSIONS: This is the first report on FBS after surgical treatment of ES. It is important to remember the possibility of the diagnosis and to maintain the patient under heavy specific medication, sometimes for longer periods.

Reconstruction of upper digestive tract: reducing morbidity by laparoscopic pull-up.

BACKGROUND: Gastric pull-up is a useful method for reconstruction of the upper digestive tract, with considerable morbidity/mortality, especially in esophageal cancers (EC). OBJECTIVE: To analyze the experience of a multidisciplinary team with a laparoscopic gastric pull-up (LGPU) method, with or without thoracoscopy, in a series of 120 patients with EC. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: From 1992 to 2004, 120 EC [cervical/cervicothoracic (3.0%), middle third (15.0%), and inferior third (82.0%)]. Most were squamous cell carcinomas (47.0%) and adenocarcinomas (34.0%). Stomach was dissected and mobilized exclusively by laparoscopy. Occasionally, laparoscopic approach was extended cranially, until connecting with cervical dissection. In other cases, dissection of thoracic esophagus was accomplished through a thoracoscopic approach. RESULTS: Eighty-one patients (68.0%) had LGPU; 39 (32.0%) needed thoracoscopy. Mortality was 5.9%. Complications were fistula (10.0%) and pneumonia (10.0%). All fistulae closed spontaneously; 89.2% of patients could swallow a normal oral diet. CONCLUSION: Low morbidity/mortality of LGPU for EC compared favorably with conventional techniques.

Diagnosis of suspicious thyroid nodules using four protein biomarkers.

PURPOSE: Fine-needle aspiration (FNA) cytology, a standard method for thyroid nodule diagnosis, cannot distinguish between benign follicular thyroid adenoma (FTA) and malignant follicular thyroid carcinoma (FTC). Previously, using expression profiling, we found that a combination of transcript expression levels from DDIT3, ARG2, C1orf24, and ITM1 distinguished between FTA and FTC. The goal of this study was to determine if antibody markers used alone or in combination could accurately distinguish between a wider variety of benign and malignant thyroid lesions in fixed sections and FNA samples. EXPERIMENTAL DESIGN: Immunohistochemistry was done on 27 FTA, 25 FTC, and 75 other benign and malignant thyroid tissue sections using custom antibodies for chromosome 1 open reading frame 24 (C1orf24) and integral membrane protein 1 (ITM1) and commercial antibodies for DNA damage-inducible transcript 3 (DDIT3) and arginase II (ARG2). FNA samples were also tested using the same antibodies. RNA expression was measured by quantitative PCR in 33 thyroid lesions. RESULTS: C1orf24 and ITM1 antibodies had an estimated sensitivity of 1.00 for distinguishing FTA from FTC. For the expanded analysis of all lesions studied, ITM1 had an estimated sensitivity of 1.00 for detecting malignancy. Because all four cancer biomarkers did well, producing overlapping confidence intervals, not one best marker was distinguished. Transcript levels also reliably predicted malignancy, but immunohistochemistry had a higher sensitivity. Malignant cells were easily detected in FNA samples using these markers. CONCLUSIONS: We improved this diagnostic test by adding C1orf24 and ITM1 custom antibodies and showing use on a wider variety of thyroid pathology. We recommend that testing of all four cancer biomarkers now be advanced to larger trials. Use of one or more of these antibodies should improve diagnostic accuracy of suspicious thyroid nodules from both tissue sections and FNA samples.

Double-bladed scalpel: a new option for harvesting margins in head and neck cancers.

BACKGROUND: In advanced head and neck tumors margins are very rarely comprehensively checked by frozen sections. The goal of this study was to analyze a new proposal for harvesting margins using a double-bladed scalpel. METHODS: Thirty-eight patients underwent a comprehensive resection of advanced head and neck tumors with a double-bladed scalpel. Margins were mapped and checked by frozen sections, while tumor resection continued. When positive margins were identified, they were excised again, and checked by frozen sections. RESULTS: Thirty-three patients (87%) had clear skin and soft tissue margins at frozen sections. Five patients (13%) had focal skin and soft tissue-positive margins at frozen sections, which were re-excised. Two patients (5%) had skin and soft tissue-positive margins only at permanent sections. One was reoperated and 1 received radiation therapy. The 3-year local control rate was 58%. CONCLUSIONS: In this preliminary study, the double-bladed scalpel appeared to be an interesting option for complete intraoperative evaluation of surgical margins of advanced head and neck tumors.

Incidência de malignidade na doença nodular da tiróide com baixa suspeita clínica: estudo observacional prospectivo por dois anos numa coorte de 50 pacientes / Incidence of malignant lesions in patients with clinically benign thyroid nodules: observational and prospective study in a cohort of 50 patients followed during two years

OBJETIVOS: Verificar a ocorrência de lesões malignas em pacientes com nódulos tiroidianos clinicamente benignos e o valor da repetição da citologia aspirativa da tiróide (PAAF). MÉTODOS: Estudo observacional prospectivo por 2 anos em coorte de 50 mulheres com nódulos tiroidianos clinicamente benignos, com exame clínico, ultra-sonografia (US) e PAAF inicial, seguidas por acompanhamento clínico, US e repunção dos mesmos nódulos (PAAF2). RESULTADOS: A palpação não é bom método para o seguimento dos nódulos quando comparada ao US. O quadro clínico foi parâmetro de confiança, pois 47/50 pacientes (94 por cento) evoluíram sem malignidade durante o seguimento. PAAF1 e PAAF2 concordaram em 33/39 pacientes quando PAAF1 foi negativa (85 por cento); 11 pacientes foram operadas, 8 por PAAF suspeita e 3 por aumento do volume nodular durante o seguimento. O anátomo-patológico (AP) foi benigno nas lesões suspeitas (8 adenomas e 3 bócios colóides). Houve 2 casos de microcarcinoma papilífero não invasivo em área distante dos nódulos e 1 caso de carcinoma papilífero não invasivo em bócio multi-nodular. CONCLUSÕES: Houve concordância entre características clínicas de benignidade com PAAF, US e acompanhamento clínico ou cirurgia; numa paciente encontramos carcinoma papilífero. O US deve ser considerado em pacientes com suspeita de nódulos de tiróide ao exame clínico; na maioria das vezes quando o resultado da PAAF1 é negativo para malignidade, o segundo exame citológico confirma o primeiro.

[Incidence of malignant lesions in patients with clinically benign thyroid nodules: observational and prospective study in a cohort of 50 patients followed during two years]. / Incidência de malignidade na doença nodular da tiróide com baixa suspeita clínica: estudo observacional prospectivo por dois anos numa coorte de 50 pacientes.

INTRODUCTION: To study the frequency of malignant lesions in patients with clinically benign thyroid nodules and the value of the repetition of fine needle aspiration biopsy (FNAB). METHODS: Observational and prospective 2-year study in a cohort of 50 patients with clinically benign thyroid nodules. Patients were initially submitted to clinical examination, ultrasound (US) and FNAB1 patients, followed by a second FNAB and US. RESULTS: Palpation is not a good test for diagnosis and follow-up of thyroid nodules. On the other hand, the initial consideration that these patients should harbor benign lesions is a very useful parameter, since 47/50 patients (94%) did not present malignant lesions during the follow-up. FNAB1 and FNAB2 were concordant in 33/39 patients when FNAB1 was negative (85%); 11 patients were operated, 8 by suspicious FNAB and 3 due to nodule growth. We observed 2 patients with non-invasive papillary microcarcinoma and 1 patient with papillary carcinoma outside of the main nodules. CONCLUSION: there was concordance between initial clinical benign diagnosis, FNAB and the follow-up. In one case there was a papillary carcinoma. In addition, ultrasonography should be considered for all patients with suspected thyroid nodules. Finally, we demonstrated that a second cytology usually confirms the result of the first cytology in benign thyroid nodules.