RESUMO
INTRODUCTION: Helicobacter pylori-infected individuals may present low-density infection, undetectable by conventional tests such as histology, rapid urease test, or urea breath test. Droplet digital polymerase chain reaction (ddPCR) is more sensitive than other polymerase chain reaction methods. We aimed to evaluate the ability of ddPCR to detect H. pylori infection in patients diagnosed as negative by conventional tests. METHODS: Dyspeptic patients (n = 236) were tested for H. pylori by histology, urea breath test, and rapid urease test. Patients were classified as having 3 positive (n = 25, control group), 2 positive (n = 12), one positive (n = 41), or zero positive (n = 158) diagnostic tests. DNA was extracted from gastric biopsies. Triplicate ddPCR testing for each of the 16S rDNA, ureA, and vacA(s) genes was performed using a QX200 ddPCR system (Bio-Rad). A gene was considered positive when detected by at least 2 of 3 repeated ddPCRs. H. pylori positivity was defined as having 2 or more positive genes. RESULTS: All the biopsies of the control patients were positive for all 3 16S rDNA, ureA, and vacA(s) genes. H. pylori infection was detected in 57 (36%), 22 (54%), and 9 (75%) patients with zero, 1, and 2 positive diagnostic tests, respectively. The density of infection was 5, 121, 599, and 3,133 copies of H. pylori genome equivalents for patients with zero, 1, and 2 of 3 positive test results and for the control group, respectively. DISCUSSION: ddPCR detected low-density "occult" H. pylori infection in a significant proportion (36%) of patients diagnosed as negative by conventional methods. The number of conventional positive tests was related to the density of infection.
Assuntos
Dispepsia/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Adulto , Idoso , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Biópsia , Testes Respiratórios , DNA Bacteriano/isolamento & purificação , Dispepsia/microbiologia , Dispepsia/patologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , RNA Ribossômico 16S/genética , Urease/análise , Urease/genéticaRESUMO
Introducción: En la endoscopia digestiva alta de pacientes con cirrosis hepática a menudo se observan lesiones inespecíficas, que se suelen orientar como gastropatía por hipertensión portal (GHP). Sin embargo, el diagnóstico de GHP puede ser difícil, tanto endoscópica como histológicamente. El estudio de expresión de CD34, que realza las células endoteliales de la microvasculatura podría ayudar al diagnóstico diferencial. Los objetivos del estudio fueron evaluar la correlación entre la endoscopia y la histología en el diagnóstico de la GHP y valorar la utilidad del CD34 en el diagnóstico de la misma. Material y métodos: Se analizaron biopsias fúndicas de 100 pacientes cirróticos y 20 controles, y se realizó inmunotinción para CD34. Se compararon con las imágenes endoscópicas. Resultados: Se observó una correlación muy baja entre la histología con el diagnóstico endoscópico de GHP (kappa=0,15). Además, la medición del diámetro de los vasos gástricos realzados mediante el uso de la tinción inmunohistoquímica (CD34) no mostró buena correlación con el diagnóstico endoscópico (p=0,26) y tampoco parece aportar información relevante para el diagnóstico histológico de GHP. Discusión: Existe una baja correlación entre la histología y la endoscopia para el diagnóstico de GHP. El uso de la inmunotinción para CD34 no mejora la rentabilidad diagnóstica del estudio histológico
Introduction: Upper gastroscopy in patients with cirrhosis often reveals non-specific lesions, which are usually oriented as portal hypertensive gastropathy (PHG). However, the diagnosis of PHG can be difficult, both from an endoscopic and histological point of view. The study of CD34 expression, which enhances the endothelial cells of the microvasculature, could help the differential diagnosis. The objectives of this study were to evaluate the correlation between endoscopy and histology in the diagnosis of PHG and to assess the utility of CD34 in the diagnosis of PHG. Material and methods: The results of immunostaining with CD34 gastric fundus biopsies from 100 cirrhotic patients and 20 controls were compared with the endoscopic images. Results: The correlation between the histology and the endoscopic diagnosis of PHG was very low (kappa=0.15). In addition, the measurement of the diameter of the gastric vessels enhanced by the use of immunohistochemical staining (CD34) did not show good correlation with the endoscopic diagnosis (p=.26) and did not provide relevant information for the histological diagnosis of PHG either. Discussion: The correlation between histology and endoscopy is low for the diagnosis of PHG. The use of immunostaining for CD34 does not seem to improve the diagnostic yield of the histological study
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antígenos CD34/análise , Gastroenterologia/métodos , Hipertensão Portal/complicações , Cirrose Hepática/diagnóstico , Biópsia , Gastroenteropatias/diagnóstico , Estudos de Casos e Controles , Imuno-Histoquímica , Análise MultivariadaRESUMO
INTRODUCTION: Upper gastroscopy in patients with cirrhosis often reveals non-specific lesions, which are usually oriented as portal hypertensive gastropathy (PHG). However, the diagnosis of PHG can be difficult, both from an endoscopic and histological point of view. The study of CD34 expression, which enhances the endothelial cells of the microvasculature, could help the differential diagnosis. The objectives of this study were to evaluate the correlation between endoscopy and histology in the diagnosis of PHG and to assess the utility of CD34 in the diagnosis of PHG. MATERIAL AND METHODS: The results of immunostaining with CD34 gastric fundus biopsies from 100 cirrhotic patients and 20 controls were compared with the endoscopic images. RESULTS: The correlation between the histology and the endoscopic diagnosis of PHG was very low (kappa=0.15). In addition, the measurement of the diameter of the gastric vessels enhanced by the use of immunohistochemical staining (CD34) did not show good correlation with the endoscopic diagnosis (p=.26) and did not provide relevant information for the histological diagnosis of PHG either. DISCUSSION: The correlation between histology and endoscopy is low for the diagnosis of PHG. The use of immunostaining for CD34 does not seem to improve the diagnostic yield of the histological study.
Assuntos
Antígenos CD34/análise , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Gastropatias/diagnóstico , Gastropatias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Fundo Gástrico/irrigação sanguínea , Fundo Gástrico/imunologia , Fundo Gástrico/patologia , Gastroscopia/métodos , Humanos , Hipertensão Portal/metabolismo , Masculino , Pessoa de Meia-Idade , Estômago/patologia , Gastropatias/etiologia , Gastropatias/metabolismoRESUMO
BACKGROUND: Subcutaneous (s.c.) glucose sensors have become a key component in type 1 diabetes management. However, their usability is limited by the impact of foreign body response (FBR) on their duration, reliability, and accuracy. Our study gives the first description of human acute and subacute s.c. response to glucose sensors, showing the changes observed in the sensor surface, the inflammatory cells involved in the FBR and their relationship with sensor performance. METHODS: Twelve obese patients (seven type 2 diabetes) underwent two abdominal biopsies comprising the surrounding area where they had worn two glucose sensors: the first one inserted 7 days before and the second one 24 h before biopsy procedure. Samples were processed and studied to describe tissue changes by two independent pathologists (blind regarding sensor duration). Macrophages quantification was studied by immunohistochemistry methods in the area surrounding the sensor (CD68, CD163). Sensor surface changes were studied by scanning electron microscopy. Seven-day continuous glucose monitoring records were considered inaccurate when mean absolute relative difference was higher than 10%. RESULTS: Pathologists were able to correctly classify all the biopsies regarding sensor duration. Acute response (24 h) was characterized by the presence of neutrophils while macrophages were the main cell involved in subacute inflammation. The number of macrophages around the insertion hole was higher for less accurate sensors compared with those performing more accurately (32.6 ± 14 vs. 10.6 ± 1 cells/0.01 mm2; P < 0.05). CONCLUSION: The accumulation of macrophages at the sensor-tissue interface is related with decrease in accuracy of the glucose measure.
Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/metabolismo , Reação a Corpo Estranho/metabolismo , Macrófagos/metabolismo , Tela Subcutânea/metabolismo , Adulto , Técnicas Biossensoriais , Feminino , Reação a Corpo Estranho/etiologia , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Sistemas de Infusão de Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismoRESUMO
BACKGROUND: Current methods based on fine-needle aspiration biopsy (FNAB) are not sufficient to distinguish among follicular thyroid lesions, follicular adenoma (FA), follicular thyroid carcinoma (FTC), and the follicular variant of papillary thyroid cancer (FVPTC). Furthermore, none of the immunohistochemical markers currently available are sensitive or specific enough to be used in the clinical setting, necessitating a diagnostic hemithyroidectomy. The aim of this study was to identify proteins of value for differential diagnosis between benign and malignant thyroid follicular lesions. METHODS: This retrospective analysis is based on an assessment of the immunoexpression of 19 proteins on 81 benign thyroid lesions (FA) and 50 malignant tumors (FTC/FVPTC). The resulting expression profile allowed the design of a scoring system model to improve the differential diagnosis of benign and malignant thyroid lesions. The model was validated using an independent series of 69 FA and 40 FTC and an external series of 40 nodular hyperplasias, and was further tested in a series of 38 FNAB cell blocks. RESULTS: A model based on the nuclear and cytoplasmic expression of APLP2, RRM2, and PRC1 discriminated between benign and malignant lesions with 100% sensitivity in both main and validation groups, with specificities of 71.3% and 50.7%, respectively. For the nodular hyperplasia series, specificity reached 94.8%. Finally, in FNAB samples, the sensitivity was 100% and the specificity was 45% for discrimination between benign and malignant lesions. CONCLUSIONS: These findings suggest that the identified APLP2, RRM2, and PRC1 signature could be useful for distinguishing between benign (FA) and malignant (FTC and FVPTC) tumors of the thyroid follicular epithelium.
Assuntos
Adenoma/diagnóstico , Precursor de Proteína beta-Amiloide/metabolismo , Carcinoma Papilar/diagnóstico , Proteínas de Ciclo Celular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ribonucleosídeo Difosfato Redutase/metabolismo , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha Fina , Carcinoma Papilar/metabolismo , Carcinoma Papilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologiaRESUMO
INTRODUCCIÓN: Recientemente, se ha constituido en Cataluña el Consorcio para el Estudio de Cáncer de Tiroides (CECaT). Se trata de una plataforma que reúne 20 hospitales y un instituto de investigación de la comunidad. Una de sus iniciativas ha sido la realización de un estudio retrospectivo de las características de pacientes tratados de cáncer diferenciado de tiroides (CDT). MATERIAL Y MÉTODOS: Se incluyeron 1.855 pacientes de 11 hospitales tratados en el periodo (1998-2012). RESULTADOS: Del total, 1.470 (79,2%) eran mujeres. La edad media al diagnóstico fue de 47,7 (15,7) años, siendo significativamente mayor en los varones que en las mujeres, 49,3 (15) versus 47,3 (15,8); p = 0,02. El 88,9% eran carcinomas papilares. El tamaño del tumor fue de 21,5 (16) mm, siendo significativamente menor en las mujeres que en los hombres, 20,1 (14,5) mm y 26,6 (20,3) mm, respectivamente (p < 0,001). Tras un seguimiento de 5,5 (3,8) años, se disponía de la situación final en 1.355 pacientes. De ellos, 1.065 (78,6%) se encontraban libres de enfermedad, 239 (17,6%) mantenían enfermedad activa y 51 (3,8%) habían fallecido. El riesgo de no estar libre de enfermedad se relacionaba de forma significativa con: mayor edad al diagnóstico, sexo masculino, mayor tamaño del tumor, metástasis linfáticas iniciales, ausencia de signos de tiroiditis en el resto de la glándula, y presencia de invasión vascular y/o extraglandular del tumor. CONCLUSIONES: Los resultados muestran que las características del CDT de la cohorte son similares a las descritas en otros ámbitos geográficos
INTRODUCTION: The consortium for the study of thyroid cancer (CECaT), including 20 hospitals and one research institute, was recently created in Catalonia (Spain). One of the first initiatives of the group was to perform a descriptive analysis of the characteristics of patients with differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: The cohort included 1,855 patients from 11 hospitals treated over a period of 15 years (1998-2012). RESULTS: In this series, 1.470 (79.2%) patients were women. Mean age was 47.7 (15.7) years old. Age was significantly higher in male than in female patients, 49.3 (15) versus 47.3 (15.8); p = 0.02. Papillary thyroid carcinoma accounted for 88.9% of cases. Mean tumor size was 21.5 (16) mm, and was significantly lower in females than in males, 20.1 (14.5) mm and 26.6 (20.3) mm respectively (p < 0.001). After a follow-up period of 5.5 (3.7) years, information was available for 1,355 patient, of whom 1065 (78.6%) were free of disease, 239 (17.6%) had no tumor persistence, and 51 (3.8) % had died. The risk of persistent or recurrent disease was significantly associated to older age at diagnosis, male gender, larger tumor size, lymph node metastases at surgery, no signs of thyroiditis in the remaining thyroid tissue, and presence of vascular and/or extraglandular invasion. CONCLUSIONS: Patient characteristics analyzed are similar to those reported in other parts of the world
Assuntos
Adulto , Feminino , Humanos , Masculino , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Carcinoma Papilar/patologia , Metástase Linfática/patologia , Tireoidite/patologiaRESUMO
BACKGROUND AND AIMS: The ability of noninvasive methods to predict the development of cirrhosis has not been established. We evaluated the ability of three noninvasive methods [the Forns index, the aspartate aminotransferase-to-platelet ratio index (APRI), and the Non-Invasive Hepatitis-C-related Cirrhosis Early Detection (NIHCED) score] to determine the risk of developing cirrhosis in chronic hepatitis C. METHODS: Consecutive patients with chronic hepatitis C who had undergone liver biopsy between 1998 and 2004 were eligible. We used the three methods to evaluate patients at baseline and at follow-up (4-10 years later). When these methods yielded discordant or indeterminate results, a second liver biopsy was performed. Logistic regression models were fitted for each method to predict whether cirrhosis would appear and to predict long-term mortality from cirrhosis. RESULTS: We included 289 patients in our study. The mean scores at baseline and at follow-up, respectively, were as follows: Forns, 5.47 ± 1.95 and 6.56 ± 2.02; APRI, 1.1 ± 2.33 and 1.4 ± 1.53; and NIHCED, 7.79 ± 11.45 and 15.48 ± 15.28. The area under the receiver operating characteristic curve for predicting cirrhosis was 0.83 for Forns, 0.79 for APRI, and 0.76 for NIHCED. The sensitivity and specificity for predicting cirrhosis, respectively, were 75 and 71% for Forns (cutoff 4.7), 86 and 42% for APRI (cutoff 0.48), and 41 and 82% for NIHCED (cutoff 0). The area under the receiver operating characteristic curve for predicting mortality was 0.86 for Forns, 0.79 for APRI, and 0.84 for NIHCED. CONCLUSION: Indirect noninvasive markers could help identify patients with chronic hepatitis C at risk of progression to cirrhosis.
Assuntos
Aspartato Aminotransferases/sangue , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Contagem de Plaquetas , gama-Glutamiltransferase/sangue , Adulto , Idoso , Biomarcadores/sangue , Biópsia , Progressão da Doença , Feminino , Seguimentos , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , EspanhaRESUMO
INTRODUCTION: The consortium for the study of thyroid cancer (CECaT), including 20 hospitals and one research institute, was recently created in Catalonia (Spain). One of the first initiatives of the group was to perform a descriptive analysis of the characteristics of patients with differentiated thyroid carcinoma (DTC). PATIENTS AND METHODS: The cohort included 1,855 patients from 11 hospitals treated over a period of 15 years (1998-2012). RESULTS: In this series, 1.470 (79.2%) patients were women. Mean age was 47.7 (15.7) years old. Age was significantly higher in male than in female patients, 49.3 (15) versus 47.3 (15.8); p=0.02. Papillary thyroid carcinoma accounted for 88.9% of cases. Mean tumor size was 21.5 (16) mm, and was significantly lower in females than in males, 20.1 (14.5) mm and 26.6 (20.3) mm respectively (p<0.001). After a follow-up period of 5.5 (3.7) years, information was available for 1,355 patient, of whom 1065 (78.6%) were free of disease, 239 (17.6%) had no tumor persistence, and 51 (3.8) % had died. The risk of persistent or recurrent disease was significantly associated to older age at diagnosis, male gender, larger tumor size, lymph node metastases at surgery, no signs of thyroiditis in the remaining thyroid tissue, and presence of vascular and/or extraglandular invasion. CONCLUSIONS: Patient characteristics analyzed are similar to those reported in other parts of the world.
Assuntos
Neoplasias da Glândula Tireoide , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Espanha , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Fatores de TempoRESUMO
La gastropatía de la hipertensión portal (GHP) es una complicación de la hipertensión portal (HTP) generalmente asociada a la cirrosis hepática (CH). Su etiopatogenia no está clara; se acepta, sin embargo, que la presencia de HTP es un factor imprescindible para su desarrollo. La GHP puede ser asintomática o manifestarse en forma de anemia ferropénica o hemorragia digestiva. Las lesiones endoscópicas varían desde un patrón en mosaico hasta manchas rojas difusas en los casos más graves; la localización más característica es el fundus. El tratamiento está indicado en caso de hemorragia, aguda o crónica como profilaxis secundaria. No hay datos suficientes para recomendar profilaxis primaria en pacientes que no han sangrado. Pueden utilizarse fármacos que disminuyen la presión portal, como los betabloqueantes no cardioselectivos, y/o tratamientos endoscópicos ablativos, como el argón. El papel del transarterial intrahepatic portosistemic shunt o shunt intrahepático portosistémico (TIPS) o la cirugía derivativa no ha sido suficientemente analizado. Por su parte, la ectasia vascular antral es una entidad poco frecuente en la CH cuya fisiopatología todavía se desconoce. Clínicamente, se comporta igual que la GHP y a nivel endoscópico suele presentarse como manchas rojas en antro. A menudo, es necesario realizar una biopsia para diferenciarla de la GHP. No disponemos de tratamiento médico efectivo, por lo que, en pacientes sintomáticos, se recomienda tratamiento ablativo endoscópico y, en casos graves, valorar antrectomía
Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended
Assuntos
Humanos , Ectasia Vascular Gástrica Antral/complicações , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Hemorragia Gastrointestinal/etiologia , Endoscopia Gastrointestinal , Ablação por CateterRESUMO
Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended.
Assuntos
Ectasia Vascular Gástrica Antral/etiologia , Hemorragia Gastrointestinal/etiologia , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Anemia Ferropriva/etiologia , Gastrectomia/métodos , Ectasia Vascular Gástrica Antral/fisiopatologia , Ectasia Vascular Gástrica Antral/cirurgia , Hemorragia Gastrointestinal/fisiopatologia , Hemorragia Gastrointestinal/cirurgia , Gastroscopia , Humanos , Derivação Portossistêmica CirúrgicaRESUMO
Objective. Although differentiated thyroid cancer (DTC) usually has an indolent course, some cases show a poor prognosis; therefore, risk stratification is required. The objective of this study is to compare the predictive ability of classical risk stratification systems proposed by the European Thyroid Association (ETA) and American Thyroid Association (ATA) with the system proposed by Tuttle et al. in 2010, based on the response to initial therapy (RIT). Methods. We retrospectively reviewed 176 cases of DTC with a median follow-up period of 7.0 years. Each patient was stratified using ETA, ATA, and RIT systems. Negative predictive value (NPV) and positive predictive value (PPV) were determined. The area under receiver operating characteristic (ROC) curve was calculated in order to compare the predictive ability. Results. RIT showed a NPV of 97.7%, better than NPV of ETA and ATA systems (93.9% and 94.9%, resp.). ETA and ATA systems showed poor PPV (40.3% and 41%, resp.), while RIT showed a PPV of 70.8%. The area under ROC curve was 0.7535 for ETA, 0.7876 for ATA, and 0.9112 for RIT, showing statistical significant differences (P < 0.05). Conclusions. RIT predicts the long-term outcome of DTC better than ETA/ATA systems, becoming a useful system to adapt management strategies.
RESUMO
Thyroid cancer is a heterogeneous disease with several subtypes characterized by cytological, histological and genetic alterations, but the involvement of epigenetics is not well understood. Here, we investigated the role of aberrant DNA methylation in the development of well-differentiated thyroid tumors. We performed genome-wide DNA methylation profiling in the largest well-differentiated thyroid tumor series reported to date, comprising 83 primary tumors as well as 8 samples of adjacent normal tissue. The epigenetic profiles were closely related to not only tumor histology but also the underlying driver mutation; we found that follicular tumors had higher levels of methylation, which seemed to accumulate in a progressive manner along the tumorigenic process from adenomas to carcinomas. Furthermore, tumors harboring a BRAF or RAS mutation had a larger number of hypo- or hypermethylation events, respectively. The aberrant methylation of several candidate genes potentially related to thyroid carcinogenesis was validated in an independent series of 52 samples. Furthermore, through the integration of methylation and transcriptional expression data, we identified genes whose expression is associated with the methylation status of their promoters. Finally, by integrating clinical follow-up information with methylation levels we propose etoposide-induced 2.4 and Wilms tumor 1 as novel prognostic markers related to recurrence-free survival. This comprehensive study provides insights into the role of DNA methylation in well-differentiated thyroid cancer development and identifies novel markers associated with recurrence-free survival.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Papilar/genética , Impressões Digitais de DNA , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Neoplasias da Glândula Tireoide/genética , Adenoma/genética , Adenoma/mortalidade , Adenoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Taxa de Sobrevida , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Proteínas WT1/genética , Adulto Jovem , Proteínas ras/genéticaRESUMO
Presentamos el caso de un joven afecto de hepatitis crónica por virus B de probable adquisición perinatal que se diagnosticó de un carcinoma hepatocelular en estadío muy inicial (BCLC 0) con un pronóstico a priori muy favorable. Sin embargo, presentó una evolución rápidamente progresiva siendo exitus en pocos meses. Se conocen pocos datos que ayuden a detectar aquellos casos de rápida progresión que puedan propiciar el inicio de terapias más agresivas que impidan o controlen dicha progresión (AU)
We report the case of a young man with chronic hepatitis B infection of probable perinatal acquisition who was diagnosed with hepatocellular carcinoma at a very early stage (BCLC 0) with a highly favorable prognosis. However, the tumor progressed rapidly and the patient died within months. Currently, there are few data that could help to identify cases likely to show rapid progression and which could prompt initiation of aggressive therapies that might prevent or control such progression (AU)
Assuntos
Humanos , Masculino , Adulto , Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/patologia , Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Evolução Fatal , Hepatectomia/métodos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , Biomarcadores Tumorais/sangue , Carga ViralRESUMO
We report the case of a young man with chronic hepatitis B infection of probable perinatal acquisition who was diagnosed with hepatocellular carcinoma at a very early stage (BCLC 0) with a highly favorable prognosis. However, the tumor progressed rapidly and the patient died within months. Currently, there are few data that could help to identify cases likely to show rapid progression and which could prompt initiation of aggressive therapies that might prevent or control such progression.
Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia , Neoplasias Hepáticas/patologia , Adulto , Antivirais/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Terapia Combinada , Progressão da Doença , Doxorrubicina/administração & dosagem , Evolução Fatal , Hepatectomia/métodos , Hepatite B Crônica/complicações , Hepatite B Crônica/congênito , Hepatite B Crônica/virologia , Humanos , Interferons/uso terapêutico , Lamivudina/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Masculino , Ultrassonografia , Carga Viral , alfa-Fetoproteínas/análiseRESUMO
CONTEXT: Cerebral vasculitis in patients infected with human immunodeficiency virus (HIV) is usually related to additional or secondary infectious agents other than neoplastic diseases or HIV itself. OBJECTIVE: To describe a 31-year-old patient infected with HIV who presented with 2 recurrent, acute episodes of neurologic impairment in a 5-month period. DESIGN: Comparison of clinical and histologic data between the present case and previously published cases. SETTING: Community hospital. PATIENT: A 31-year-old, HIV-infected patient with recurrent strokes and chronic lymphocytic meningitis. INTERVENTION: After ruling out cardiac embolisms and coagulation disorders, the presence of central nervous system vasculitis, probably secondary to an infectious process, was suspected based on the clinical examination and cerebrospinal fluid abnormalities. RESULTS: Necropsy findings suggest the diagnosis of primary angiitis of the central nervous system, and the only infectious agent that could be found was HIV. CONCLUSIONS: Histologic studies were compatible with a diagnosis of primary angiitis of the central nervous system, but the pathogenic role of HIV in the genesis of the vasculitic process cannot be elucidated.