RESUMO
BACKGROUND: Videocapsule endoscopy (VCE) is considered the gold standard for overt and obscure gastrointestinal bleeding (OGIB), after negative upper and lower endoscopy. Nonetheless, VCE's diagnostic yield is suboptimal, and it represents a costly, time-consuming, and often not easily available technique. In order to evaluate bleeding risk in patients with atrial fibrillation, several scoring systems have been proposed, but their utilization outside the original clinical setting has rarely been explored. The aim of the study is to evaluate potential role of bleeding risk scoring systems in predicting the occurrence of positive findings at VCE examination, and therefore in increasing VCE diagnostic yield. METHODS: Data from consecutive patients undergoing VCE between April 2015 and June 2020 were retrospectively retrieved, and clinical and demographic characteristics were collected. HAS-BLED, ATRIA, and ORBIT scores were calculated, and patients were considered at low or high risk of bleeding accordingly. Discriminative ability of the scores for positive VCE findings has been evaluated by area under receiver operator characteristic curve (AUC) calculation. Diagnostic yield of scores in high- and low-risk patients was calculated. RESULTS: A total of 413 patients underwent VCE examination, among which 368 (89%) for OGIB. Positive findings were observed in 246 patients (67%), with angiodysplasias being the most frequent lesion (92%). The three scores displayed similar consistent discriminative ability for positive VCE findings (mean AUC = 0.69), and identified high-risk group of patients in which VCE has a higher diagnostic yield. CONCLUSIONS: In the present retrospective study, bleeding scores accurately discriminated patients with higher probability of positive findings at VCE examination. Bleeding scores utilization may help in the management of patients with OGIB, with a potential consistent resource optimization and cost-saving.
Assuntos
Fibrilação Atrial , Endoscopia por Cápsula , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologiaRESUMO
BACKGROUND: Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor. METHODS: Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy. RESULTS: By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs. CONCLUSIONS: These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Gastrointestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Carcinoma Neuroendócrino/genética , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/genética , Humanos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/patologia , PrognósticoRESUMO
Malignant gliomas are highly dependent on the isoprenoid pathway for the synthesis of lipid moieties critical for cell proliferation. The isoprenoid derivative N6-isopentenyladenosine (iPA) displays pleiotropic biological effects, including a direct anti-tumor activity in several tumor models. The antiglioma effects of iPA was then explored in U87MG cells both in vitro and grafted in mice and the related molecular mechanism confirmed in primary derived patients' glioma cells. iPA powerfully inhibited tumor cell growth and induced caspase-dependent apoptosis through a mechanism involving a marked accumulation of the pro-apoptotic BIM protein and inhibition of EGFR. Indeed, activating AMPK following conversion into its iPAMP active form, iPA stimulated EGFR phosphorylation and ubiquitination along a proteasome-mediated pathway which was responsible for receptor degradation and its downstream signaling pathways inhibition, including the STAT3, ERK and AKT cascade. The inhibition of AMPK by compound C prevented iPA-mediated phosphorylation of EGFR, known to precede receptor loss. As expected the block of EGFR degradation, by exposure to the proteasome inhibitor MG132, significantly reduced iPA-induced cell death. Given the importance of receptor degradation in iPA-mediated cytotoxicity, we also documented that the EGFR expression levels in a panel of primary glioma cells confers them a high sensitivity to iPA treatment. In conclusion our study provides the first evidence of iPA antiglioma effect. Indeed, as glioma is driven by aberrant signaling of growth factor receptors, particularly the EGFR, iPA, alone or in association with EGFR targeted therapies, might be a promising therapeutic tool to achieve a potent anti-tumoral effect.
Assuntos
Neoplasias Encefálicas/patologia , Receptores ErbB/biossíntese , Glioma/patologia , Isopenteniladenosina/farmacologia , Proteínas de Neoplasias/biossíntese , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases Ativadas por AMP/fisiologia , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/genética , Feminino , Glioma/metabolismo , Humanos , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Fosforilação/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacosRESUMO
CONTEXT: The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules. OBJECTIVE: The aim of this study was to establish whether the volume changes of benign nodules are associated with the presence of RAS mutation. PATIENTS AND METHODS: Genomic DNA obtained by fine-needle aspiration of 78 thyroid nodules with benign cytology was analysed by pyrosequencing for the presence of NRAS(61) and KRAS(13) mutations. Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation. RESULTS: A RAS mutation was found in 24 thyroid aspirates (30·8%, 8 NRAS(61) and 16 KRAS(13) ). RAS mutation was not associated with ultrasonographic features, but was significantly associated with a larger size at baseline (P = 0·017). After a 25-month mean follow-up, RAS mutation-positive nodules displayed faster growth (RAS mutation-positive vs RAS mutation-negative % annual growth 27·6% ±32·2% vs 1·0% ±17·0%, P < 0·001). CONCLUSIONS: Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild-type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management.
Assuntos
GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Glândula Tireoide/metabolismo , Nódulo da Glândula Tireoide/genética , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Modelos Lineares , Pessoa de Meia-Idade , Análise de Sequência de DNA , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Fatores de Tempo , Adulto JovemRESUMO
The endocannabinoid system, through cannabinoid receptor signaling by endocannabinoids, is involved in a wide range of functions and physiopathological conditions. To date, very little is known concerning the role of the endocannabinoids in the control and regulation of cell proliferation. An anti-proliferative action of CB1 signaling blockade in neurogenesis and angiogenesis argues in favor of proliferation-promoting functions of endocannabinoids through CB1 receptors when pro-growth signals are present. Furthermore, liver regeneration, a useful in vivo model of synchronized cell proliferation, is characterized by a peak of anandamide that elicits through CB1 receptor, the expression of critical mitosis genes. The aim of this study was to focus on the timing of endocannabinoid signaling changes during the different phases of the cell cycle, exploiting the rat liver regeneration model following partial hepatectomy, the most useful to study synchronized cell cycle in vivo. Hepatic regeneration led to increased levels of anandamide and endocannabinoid-like molecules oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the G1 phase of the cell cycle, with a concomitant increase in CB1 mRNA levels, whose protein expression peaked later during the S phase. Blocking of CB1 receptor with a low dose of the selective antagonist/inverse agonist SR141716 (0.7 mg/kg/dose) affected cell cycle progression reducing the expression of PCNA, and through the inhibition of pERK and pSTAT3 pathways. These results support the notion that the signaling mediated by anandamide through CB1 receptor may be important for the entry and progression of cells into the cell cycle and hence for their proliferation under mitogenic signals.
Assuntos
Ácidos Araquidônicos/metabolismo , Ciclo Celular , Proliferação de Células , Endocanabinoides/metabolismo , Regeneração Hepática , Fígado/metabolismo , Alcamidas Poli-Insaturadas/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Animais , Antagonistas de Receptores de Canabinoides/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glicerídeos/metabolismo , Hepatectomia , Fígado/efeitos dos fármacos , Fígado/patologia , Regeneração Hepática/efeitos dos fármacos , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
Activating mutations in RAS genes and p21 Ras overactivation are common occurrences in a variety of human tumors. p21 Ras oncoproteins deregulate a number of signaling pathways, dedifferentiating the thyroid cell, and negatively regulating the expression of thyroid specific genes. In rat thyroid cells, Ras oncoproteins inhibit the TSH pathway by reducing PKA activity and thus the expression of thyroid specific genes, while in mouse melanocytes, Ras oncoproteins reduce the αMSH-stimulated cAMP signaling by increasing the expression of the phosphodiesterase-4B. Given these cell-dependent differences, we investigated if and how the TSH/CREB pathway is modulated by Ras oncoprotein in a human thyroid cell line. CREB phosphorylation was stimulated by TSH and forskolin in TAD-2 cells. Ras(V12) expression negatively regulated the TSH-stimulated CREB phosphorylation but was ineffective on forskolin-stimulated CREB phosphorylation. Phosphodiesterase inhibition by IBMX enhanced TSH-stimulated CREB phosphorylation, but did not restore TSH-stimulated CREB phosphorylation inhibited by Ras oncoprotein. These data indicate that Ras oncoprotein disrupts the TSH/CREB pathway, upstream adenylyl cyclase, and highlight the existence of mechanisms of interaction between Ras and the cAMP pathway different in human and in rat thyroid cells.
Assuntos
Adenilil Ciclases/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Tireotropina/metabolismo , 1-Metil-3-Isobutilxantina/administração & dosagem , Animais , Linhagem Celular , AMP Cíclico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Diester Fosfórico Hidrolases/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Ratos , Transdução de Sinais/efeitos dos fármacos , Glândula Tireoide/citologia , Glândula Tireoide/metabolismoRESUMO
N6-isopentenyladenosine (iPA) is a modified adenosine with an isopentenyl moiety derived from the mevalonate pathway which displays pleiotropic biological effects, including anti-tumor and anti-angiogenic activity. Previous evidence revealed a biphasic effect of iPA on phytohemagglutinin-stimulated lymphocytes, being pro-proliferative at low doses and anti-proliferative at high doses. Analogously, we have recently shown that low iPA concentrations (<1µM) increased the immune response of natural killer (NK) cells against cancer targets. In the present study, we evaluated the effect of iPA at high concentration (10µM) on IL-2-activated NK cells. iPA, inhibited NK cell proliferation and cytotoxicity against their conventional tumor target, human K562 cells. This inhibition was associated with decreased expression and functionality of NK cell activating receptors NKp44 and NKG2D as well as impaired cyto/chemokines secretion (RANTES, MIP-1α, TNF-α and IFN-γ). ERK/MAPK and STAT5 activation in IL-2-activated NK cells were inhibited by iPA. The results obtained in vitro were validated in vivo in the inflammatory murine model of croton oil-induced ear dermatitis. The topical application of iPA significantly reduced mouse ear oedema, thus suggesting anti-inflammatory properties of this molecule. These results show the ability of iPA to exert anti-inflammatory effects both in vitro and in vivo directly targeting NK cells, providing a novel pharmacological tool in those diseases characterized by a deregulated immune-response, such as cancer or inflammatory conditions.
Assuntos
Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Interleucina-2/farmacologia , Isopenteniladenosina/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Administração Tópica , Animais , Anti-Inflamatórios/administração & dosagem , Células Cultivadas , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Humanos , Isopenteniladenosina/administração & dosagem , Células K562 , Células Matadoras Naturais/metabolismo , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 2 Desencadeador da Citotoxicidade Natural/metabolismo , Fator de Transcrição STAT5/metabolismoRESUMO
BACKGROUND: Non-suppressive or partially suppressive L-T4 treatment demonstrated to be effective in reducing the volume of the nodules. However, studies with long follow-up are lacking and significant controversy exists regarding the efficacy of non-suppressive L-T4 treatment in benign nodular goiter. AIM: The goal of this study was to determine the evolution of thyroid nodules in subjects treated with a non-suppressive levothyroxine (L-T4) dose, compared to untreated subjects. DESIGN AND PATIENTS: We followed for a period of 1-9 years the thyroid nodule size in 356 female patients in the age range 19-45 at study entry, of which 201 untreated (Group 0) and 165 treated with a non-suppressive L-T4 dose (Group L-T4). MEASUREMENTS: We determined the volume of thyroid nodules by ultrasonography. RESULTS: The initial mean nodule volume in Group 0 and Group L-T4 was 3.91 ± 6.87 and 4.01 ± 7.35 mL, respectively. Nodule volume increase was inversely correlated to the initial volume. The final volume was slightly higher in untreated than in L-T4 treated subjects (5.37 ± 8.49 and 4.39 ± 6.72 mL). In both groups, the mean of annual fold increase of nodule volume was inversely correlated with the follow-up duration (P < 0.0046), indicating a slower growth as time advances. In the subjects treated with L-T4, the mean annual increase of nodule volume was significantly minor compared to untreated subjects. Concomitant nodules in ten multinodular goiters exhibited totally independent evolution, demonstrating that intranodular factors are more important for the nodule behavior than extra nodular factors. CONCLUSIONS: Our study demonstrates that the growth of benign thyroid nodules is inversely correlated to their size, benign nodules naturally growth slowly as time advances, and that a chronic treatment with L-T4 at a non-TSH-suppressive dose significantly reduces their growth.
Assuntos
Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/tratamento farmacológico , Tiroxina/uso terapêutico , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/sangue , UltrassonografiaRESUMO
CONTEXT: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). OBJECTIVE: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. DESIGN: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. METHODS: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. RESULTS: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). CONCLUSIONS: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.
Assuntos
Estatura , Transtornos do Crescimento , Hormônio do Crescimento Humano , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Arginina , Clonidina , Transtornos do Crescimento/fisiopatologia , Transtornos do Crescimento/diagnóstico , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêuticoRESUMO
CONTEXT: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. OBJECTIVE: To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. DESIGN: Multicenter, retrospective, cohort study. SETTING: Three Italian thyroid cancer referral centers. PARTECIPANTS: 55 RR-DTC treated with lenvatinib. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 (95% CI 19.06-32.93) and 70 months (95% CI 36-111.99), respectively. Pre-treatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS (p < 0.001; HR 18.82; 95% CI 3.65-97.08: score 0-1 as reference) and OS (p = 0.001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI)-avidity was independently related to PFS (p = 0.047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Post-treatment setting: best radiological response independently predicted PFS (p = 0.001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (p = 0.013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference). CONCLUSIONS: RR-DTC with good performance status and RAI-avid disease obtain the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor.
RESUMO
CONTEXT: Radioactive iodine is a crucial tool for treatment of differentiated thyroid cancer (DTC). In 5% of cases, DTCs lose I-131 avidity and assume an aggressive behaviour. Treatment options for iodine-refractory DTC are limited. We report the experience of off-label use of the tyrosine kinase inhibitor sorafenib for treatment of advanced iodine-refractory DTC. DESIGN: Patients with progressive DTC refractory to radioactive iodine were treated with sorafenib used off-label independently from their performance status. Primary study end-points were radiological response, progression-free survival (PFS) and safety. Secondary end-points were site-specific radiological response and overall survival (OS). An exploratory analysis of the role of serum thyroglobulin (Tg) and fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed. RESULTS: A total of 17 patients were included in the study. Median follow-up was 15·5 months. Clinical benefit was obtained in 71% of subjects (30% partial response and 41% stable disease). Sorafenib was mostly well tolerated, but a high incidence of fatal events was reported (three patients died from severe bleeding events and two from cardiac arrest). Median PFS was 9 months. Median OS was 10 months. The best responses were observed in lymph nodes and lung. Baseline Tg levels and the Tg response to treatment were correlated to both radiological response and PFS. Baseline FDG-PET assessment and early FDG-PET response were correlated to radiological response. CONCLUSIONS: Sorafenib allows morphological disease control in the majority of patients with iodine-refractory DTC. Progression-free survival and overall survival were lower than in previous studies as a consequence of the worse clinical condition of our patients. Sorafenib is mostly well tolerated but could have been responsible for the reported fatal events. Baseline Tg and the Tg response to treatment could be useful for predicting morphological response and clinical outcome. Early FDG-PET response could be helpful for the timely identification of nonresponding patients.
Assuntos
Fluordesoxiglucose F18 , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Tomografia por Emissão de Pósitrons/métodos , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Resultado do TratamentoRESUMO
BACKGROUND: Concomitant papillary thyroid cancer (PTC) and Hashimoto's thyroiditis (HT) is a frequent occurrence. Whether these two conditions are linked and whether PTC with concurrent HT has distinct clinicopathological characteristics are still debated issues. Lymphocytic infiltration is abundant in HT and might be relevant in the pathogenesis and progression of PTC. BRAF(V600E) mutation is associated with a more advanced PTC at diagnosis; however, its role in the clinicopathological characteristics of PTC with concurrent HT is unknown. DESIGN AND PATIENTS: We enrolled 146 patients with histological diagnosis of PTC. Microscopic assessment of histology samples was performed to identify the presence of lymphocytic infiltration. Detection of BRAF(V600E) was performed on cytology samples by both direct sequencing and pyrosequencing, and results were correlated with clinical parameters. RESULTS: Concurrent HT lymphocytic infiltration was associated with the female gender, smaller tumour size, a less frequent extracapsular extension and a lower grade of TNM staging. BRAF(V600E) was more frequent in PTC with concomitant lymphocytic infiltration. In PTC harbouring BRAF(V600E) , concurrent lymphocytic infiltration was still associated with the female gender, a less frequent extracapsular extension and a lower TNM staging. CONCLUSIONS: These results suggest that lymphocytic infiltration of HT is a protective factor against PTC progression, and it is independent of BRAF mutational status.
Assuntos
Carcinoma Papilar/genética , Carcinoma/genética , Doença de Hashimoto/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Câncer Papilífero da TireoideRESUMO
BACKGROUND: Primary thyroid lymphomas (PTLs) account for 5% of thyroid malignant tumors and often develop in patients with Hashimoto Thyroiditis (HT). Fine-needle cytology (FNC) is widely used in the diagnosis of thyroid nodules, including those arising in HT. Two PTL cases in HT elderly patients are here described and discussed. METHODS: FNC was performed in rapidly enlarged thyroid nodules of 2 elderly patients under ultrasound (US) control. FNC was used to prepare conventional cytologic smears, immunocytochemistry (ICC) and flow cytometry (FC) assessment of cell populations. RESULTS: The above cases were diagnosed as well differentiated, small B-cell and diffuse large B-cell thyroid lymphomas, respectively, by means of FNC. The histological diagnoses were mucosa-associated non Hodgkin lymphoma (MALT) and diffuse large B-cell lymphoma (DLBCL), confirming FNC diagnoses, and patients were treated accordingly. CONCLUSIONS: FNC diagnosis of PTL is reliable and accurate; it may be conveniently used in the clinical practice since it provides indications for appropriate therapeutic procedures or diagnostic surgery, and avoids to treat benign nodules.
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Detecção Precoce de Câncer , Linfoma não Hodgkin/patologia , Neoplasias da Glândula Tireoide/patologia , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Estadiamento de NeoplasiasRESUMO
Choriocarcinoma is a germ cell tumor containing syncytiotrophoblastic cells and secreting human Beta-HCG. Primary choriocarcinoma of the lung is extremely uncommon. The prognosis of this tumor is extremely poor, despite surgical and chemotherapeutic treatment. We report a surgically treated case of choriocarcinoma in a 37-year-old woman who came to our attention because of a isolated lung lesion. The tumor was successfully resected. Chemotherapy was started 2 months after thoracic surgery and consisted of bleomycin, etoposide, and cisplatin. At 1-year follow-up the patient is alive in good condition. The hCG level is actually normal.
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Coriocarcinoma , Neoplasias Pulmonares , Adulto , Coriocarcinoma/diagnóstico , Coriocarcinoma/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgiaRESUMO
Pulmonary sequestration is an uncommon disease, accounting for only approximately 1.5% of all congenital pulmonary malformations. In most cases, the diagnosis is a result of accidental radiological findings; it is rarely accompanied by clinical symptoms, and is more commonly associated with other congenital malformations. Herein, we reported a case of pulmonary sequestration presented as massive left hemothorax and associated with primary lung sarcoma. A pneumonectomy via thoracotomy was attended with complete resection of sequestration and of sarcoma. The postoperative course was unremarkable, and the patient was discharged on postoperative day 11.
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Sequestro Broncopulmonar/complicações , Fibrossarcoma/complicações , Hemotórax/etiologia , Neoplasias Pulmonares/complicações , Adulto , Sequestro Broncopulmonar/diagnóstico , Feminino , HumanosRESUMO
BACKGROUND: Fibrosarcoma (FS) accounts for about 3% of all soft tissue sarcomas. It may arise in any area of the body, but it is relative rare in the head and neck district. Fine-needle cytology (FNC) is widely used in the diagnosis of neoplastic and non-neoplastic lesions of soft tissue. This article describes a case of FS of the neck diagnosed by FNC. METHODS: FNC was performed in a sub-fascial supraclavicular mass of an elderly patient under ultrasound (US) control. FNC was used to prepare cytological smears that were conventionally and immunocytochemically (ICC) stained. RESULTS: Smears showed a monomorphous spindle cell population and were positive at ICC for Vimentin and negative for CKAE1AE3, Actin, S-100, CD68, CT and PAX-8. The cytological diagnosis was confirmed by histological diagnosis. The patient underwent surgical resection and subsequent radiotherapy. CONCLUSIONS: FNC diagnosis of FS is reliable and accurate and may be conveniently used in the scheduling of surgical procedures, when needed, avoiding the treatment of benign nodules.
Assuntos
Fibrossarcoma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Idoso , Humanos , MasculinoRESUMO
BACKGROUND: Amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils in different organs and tissues. The thyroid gland may be affected by diffuse or nodular amyloid deposits, along with multiple myeloma (MM) (Amyloid Light-Chain Amyloidosis, AL amyloidosis) or chronic inflammatory diseases (Amyloid A Amyloidosis, AA amyloidosis), but thyroid gland involvement rarely appears as the first clinical manifestation in both conditions. The present study reports a case of primary thyroidal nodular amyloid goiter diagnosed by fine-needle cytology (FNC) in an elderly patient. CASE REPORT: A 66-year-old female patient presented with dysphagia and hoarseness; the patient suffered from rheumatoid arthritis but did not have kidney failure or altered thyroid function. Ultrasound examination (US) showed a 30 mm irregular, hypoechoic area in the left thyroid lobe. FNC showed abundant, dense and amorphous material similar to the one stained in purple at Diff-Quik stain and pinkish at the Papanicolaou. Spindle cells with thin, bland and bent nuclei were scattered in this material; few thyroid follicular cells were also present. An alcohol-fixed smear was stained with Congo red: the amyloid material appeared cherry red and it also showed apple-green birefringence when observed with a polarizing microscope. A differential diagnosis between different thyroid pathologies was considered and the cytological diagnosis of nodular amyloid goiter was pointed out. The patient underwent thyroid lobectomy and the subsequent histological examination confirmed the cytological diagnosis. CONCLUSIONS: FNC is a safe and effective procedure for the diagnosis of thyroid amyloidosis. Congo red-stained smears can be used to demonstrate the presence of amyloid material, showing the typical green birefringence under polarized light. An early and accurate cytological diagnosis may suggest an hematological screening and the appropriate treatment for the thyroid nodule.
Assuntos
Amiloide/metabolismo , Bócio Nodular/metabolismo , Idoso , Biópsia por Agulha Fina , Feminino , HumanosRESUMO
Descending necrotizing mediastinitis is a life-threatening complication of an oropharyngeal infection that requires prompt and aggressive medical and surgical therapy. Herein, we report unusual case of man suffering of sub-acute mediastinal infection due to odontoiatric abscess which exacerbated at 3 months after its first presentation. Chest X-ray and CT scan demonstrated soft-tissue swelling of the neck and encapsulated fluid collections with gas bubbles within anterior mediastinum, especially on the right side. Bilateral anterior neck dissections were performed and blunt dissection, irrigation and debridement were carried out to several centimetres below the sternal manubrium. Then, right standard thoracotomy was performed with debridement of the anterior mediastinum. Four tubes were placed in the mediastinum and pleural cavity on the right side, and two tubes were placed in the left thoracic cavity. Follow-up CT scans of neck and chest showed the resolution of infection.
Assuntos
Infecções Bacterianas/cirurgia , Mediastinite/microbiologia , Mediastinite/cirurgia , Mediastino/patologia , Mediastino/cirurgia , Doença Aguda , Idoso de 80 Anos ou mais , Desbridamento , Progressão da Doença , Humanos , Masculino , NecroseRESUMO
The mechanical stapler is routinely used in thoracic surgery practice to attend resection of bronchus and vessels. Herein, we reported a very rare complication as the migration of a titanium surgical clip through a right lobectomy stump. One year after the procedure, the patient complained of persistent cough. A misdiagnosis of asthma was made and she treated for 6 months with bronchodilators, corticosteroid and antihistaminic without success. Thus, patient re-referred of our unit. No clinical signs of infection as fewer, productive cough, dyspnea were present. The laboratory exams were within normal value including white cells. CT scan revealed no abnormalities. Bronchoscopy demonstrated a healed upper bronchus stump without evidence of an actual, open bronchopleural fistula but with clips apparently working their way into the airway, with approximately half of the clip visible within the lumen. The side of the clips that would be open before closure by the surgeon formed the leading edge of the clips visible in the lumen. The clips were successfully removed during flexible bronchoscopy with a forceps usually used for biopsy. After the procedure, the cough disappeared. The endoscopy check after 3 months showed a normal bronchial stump without evidence of fistula.
Assuntos
Asma/diagnóstico , Migração de Corpo Estranho/diagnóstico , Pulmão/cirurgia , Pneumonectomia , Complicações Pós-Operatórias/diagnóstico , Suturas , Idoso , Broncoscopia , Diagnóstico Diferencial , Feminino , Migração de Corpo Estranho/cirurgia , Humanos , Complicações Pós-Operatórias/cirurgia , SíndromeRESUMO
BACKGROUND: Ultrasound is considered the best diagnostic method for the detection of metastatic cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). According to current guidelines, all patients undergoing thyroidectomy for malignancy should undergo preoperative neck ultrasound of the thyroid and central and lateral neck LNs, followed by fine needle aspiration of suspicious LNs. Cervical LN involvement determenes the extent of surgery. Complete surgical resection disease at the initial operation decreases likelihood of future surgery for recurrent disease and may impact survival. We use a new technique, B-flow imaging (BFI), recently used for evaluation of thyroid nodules, to estimate the presence of BFI twinkling signs (BFI-TS), within metastatic LNs in patients with PTC. METHODS: Between September 2006 and December 2012, 304 patients with known PTC were examined for preoperative sonographic evaluation with gray-scale US, color Doppler US and BFI. Only 157 with at least one metastatic LN were included in our study. All patients included underwent surgery, and the final diagnosis was based on the results of histologic examination of the resected specimens. The following LN characteristics were evaluated: LN shape, abnormal echogenicity, the absent of hilum, calcifications, cystic appearance, peripheral vascularization and the presence of BFI-TS. RESULTS: A total of 767 LNs were analyzed. 329 out of 767 were metastatic, according to the histopathologic findings. BFI-TS, showed 99.5% specificity and 81,5% sensitivity. We detected BFI-TS in 6 metastatic LNs that were negative to the other conventional US features. CONCLUSIONS: Our results indicate that the BFI-TS has a diagnostic accuracy higher than the other conventional sonographic signs. Our findings suggest that BFI can be helpful in the selection of suspicious neck LNs that should be examined at cytologic examination or open biopsy for accurate preoperative staging and individual therapy selection.