Analysis of Milk Using a Portable Potentiometric Electronic Tongue Based on Five Polymeric Membrane Sensors.

A portable potentiometric electronic tongue (PE-tongue) was developed and applied to evaluate the quality of milk with different fat content (skimmed, semi-skimmed, and whole) and with different nutritional content (classic, calcium-enriched, lactose-free, folic acid-enriched, and enriched in sterols of vegetal origin). The system consisted of a simplified array of five sensors based on PVC membranes, coupled to a data logger. The five sensors were selected from a larger set of 20 sensors by applying the genetic algorithm (GA) to the responses to compounds usually found in milk including salts (KCl, CaCl2, and NaCl), sugars (lactose, glucose, and galactose), and organic acids (citric acid and lactic acid). Principal component analysis (PCA) and support vector machine (SVM) results indicated that the PE-tongue consisting of a five-electrode array could successfully discriminate and classify milk samples according to their nutritional content. The PE-tongue provided similar discrimination capability to that of a more complex system formed by a 20-sensor array. SVM regression models were used to predict the physicochemical parameters classically used in milk quality control (acidity, density, %proteins, %lactose, and %fat). The prediction results were excellent and similar to those obtained with a much more complex array consisting of 20 sensors. Moreover, the SVM method confirmed that spoilage of unsealed milk could be correctly identified with the simplified system and the increase in acidity could be accurately predicted. The results obtained demonstrate the possibility of using the simplified PE-tongue to predict milk quality and provide information on the chemical composition of milk using a simple and portable system.

Promoting laccase sensing activity for catechol detection using LBL assemblies of chitosan/ionic liquid/phthalocyanine as immobilization surfaces.

The performance of electrochemical laccase-based biosensors can be improved by immobilizing the enzyme on composite Layer-by-Layer (LbL) supports in which materials with complementary functions are combined. LbL films are formed by layers combining an electrocatalytic material which favors electron transfer (sulfonated copper phthalocyanine, CuPcS(-)), an ionic liquid which enhances the electrical conductivity of the layers (1-butyl-3-methylimidazolium tetrafluoroborate, IL(+)) and a material able to promote enzyme immobilization (chitosan, CHI(+)). Composite films with different structures have been demonstrated to be efficient electrocatalysts, producing an increase in the magnitude of the responses towards catechol. The most intense and reproducible electrocatalytic effect was observed when a layer of the CuPcS(-) was placed on top of a layer formed by a mixture of CHI(+) + IL(+) to obtain [CHI(+) + IL(+)|CuPcS(-)]2 films. Biosensors with laccase immobilized on the surface of the LbL layers [CHI(+) + IL(+)|CuPcS(-)]2|Lac showed mediated electron transfer between the redox enzyme and the film and a reproducibility of device-to-device performance of 4.1%. The amperometric biosensor showed a sensitivity of 0.237 A·M-1 and a linear detection range from 2.4 µM to 26 µM for catechol. The excellent Limit of detection (LOD) of 8.96·10-10 M (3·σ /m) is one order of magnitude lower than that obtained in similar studies. A Michaelis-Menten constant of 3.16 µM confirms excellent enzyme-substrate affinity.

Analysis of musts and wines by means of a bio-electronic tongue based on tyrosinase and glucose oxidase using polypyrrole/gold nanoparticles as the electron mediator.

A bioelectronic tongue (bioET) based on combinations of enzymes (tyrosinase and glucose oxidase) and polypyrrole (Ppy) or polypyrrole/AuNP (Ppy/AuNP) composites was build up and applied to the analysis and discrimination of musts and wines. Voltammetric responses of the array of sensors demonstrated the effectiveness of polymers as electron mediators and the existence of favorable synergistic effects between Ppy and the AuNPs. Using Principal Component Analysis and Parallel Factor Analysis it was possible to discriminate musts according to the °Brix and TPI (Total Polyphenol Index), and wines according to the alcoholic degree and TPI. Partial Least Squares provided good correlations between the bioET output and traditional chemical parameters. Moreover, Support Vector Machines permitted to predict the TPI and the alcoholic degree of wines, from data provided by the bioET in the corresponding grapes. This result opens the possibility to predict wine characteristics from the beginning of the vinification process.

Analysis of organic acids and phenols of interest in the wine industry using Langmuir-Blodgett films based on functionalized nanoparticles.

A chemically modified electrode consisting of Langmuir-Blodgett (LB) films of n-dodecanethiol functionalized gold nanoparticles (SDODAuNP-LB), was investigated as a voltammetric sensor of organic and phenolic acids of interest in the wine industry. The nanostructured films demonstrated interfacial properties being able to detect the main organic acids present in grapes and wines (tartaric, malic, lactic and citric). Compared to a bare ITO electrode, the modified electrodes exhibited a shift of the reduction potential in the less positive direction and a marked enhancement in the current response. Moreover, the increased electrocatalytic properties made it possible to distinguish between the different dissociable protons of polyprotic acids. The SDODAuNP-LB sensor was also able to provide enhanced responses toward aqueous solutions of phenolic acids commonly found in wines (caffeic and gallic acids). The presence of nanoparticles increased drastically the sensitivity toward organic acids and phenolic compounds. Limits of detection as low as 10(-6) mol L(-1) were achieved. Efficient catalytic activity was also observed in mixtures of phenolic acid/tartaric in the range of pHs typically found in wines. In such mixtures, the electrode was able to provide simultaneous information about the acid and the phenol concentrations with a complete absence of interferences. The excellent sensing properties shown by these sensors could be attributed to the electrocatalytic properties of the nanoparticles combined with the high surface to volume ratio and homogeneity provided by the LB technique used for the immobilization. Moreover, the LB technique also provided an accurate method to immobilize the gold nanoparticles giving rise to stable and reproducible sensors showing repeatability lower than 2% and reproducibility lower than 4% for all the compounds analyzed.

Impacto de las metástasis óseas en 47 pacientes con cáncer diferenciado de tiroides / Outcome of Bone Metastases in 47 Patients with Differentiated Thyroid Cancer

Las metástasis a distancia ocurren en el 10 % de los pacientes con carcinoma diferenciado de tiroides (CDT). Las metástasis óseas (MO) son las segundas en frecuencia, luego de las pulmonares. Son causa de morbilidad significativa y su manejo es complejo. Objetivo: Revisar la experiencia en el diagnóstico y tratamiento de pacientes con MO evaluados en 10 centros asistenciales. Material y métodos: Estudio retrospectivo multicéntrico. Criterio de inclusión: presencia de MO en pacientes con CDT, diagnosticada por a) biopsia de la lesión, b) lesión estructural ósea con captación de 131I asociada a Tiroglobulina (Tg) elevada o c) lesión estructural ósea captante de (fluor-deoxi-glucosa) 18FDG en (Tomografía por emisión de positrones) PET-TC y Tg elevada. Se evaluaron datos extraídos de la revisión de historias clínicas. Resultados: Se incluyeron 47 pacientes, 55 % mujeres; edad: mediana 55 años (rango 15-84). La histología fue carcinoma papilar en 55 %, folicular en 32 % y otros tipos en 13 %. El diagnóstico de las MO fue sincrónico en 47 % y metacrónico en 53 %, estas últimas detectadas en promedio a los 72 meses (7-240) luego del diagnóstico inicial. Las MO fueron sintomáticas en 64 %. El síntoma más frecuente fue el dolor (70 %). La localización más frecuente fue la vertebral (36 %), con compromiso de múltiples sitios en el 68% de los casos. Dieciséis pacientes (34 %) tuvieron además persistencia/recurrencia locorregional y 68 % metástasis en otras localizaciones, siendo la más frecuente la pulmonar (90 %). Los niveles de Tg estimulada se obtuvieron en 38 pacientes; fueron > 100 ng/ml en 87 % y <100 ng/ml en 13 %. La calcemia fue normal en todos los casos. Los marcadores de remodelado óseo estuvieron elevados en 9 de 31 pacientes (29 %). Los tratamientos efectuados fueron 131I (78 %), bifosfonatos (64 %), cirugía (53 %), radioterapia externa (55 %) y otras modalidades (23 %). La mediana de seguimiento fue de 24 meses (1-228). La sobrevida fue de 41 %. Un paciente fue considerado sin evidencia de enfermedad. Veintiocho pacientes (59 %) murieron con enfermedad. La causa de muerte se conoció en 27 casos, relacionándose con las MO en 8 casos (30 %). Conclusiones: Las MO se observaron predominantemente en pacientes >45 años, con una distribución similar por sexo. Fueron múltiples a predomino axial, ocasionando morbilidad en la mayoría de los pacientes. Los marcadores de remodelado óseo estuvieron elevados en un tercio de los casos evaluados. Ningún paciente presentó hipercalcemia. El tratamiento incluyó múltiples modalidades, lo que demuestra la importancia del enfoque multidisciplinario en estos pacientes. Aunque las MO se asociaron a enfermedad incurable, la mortalidad se relacionó principalmente con la diseminación en otras localizaciones del CDT. Rev Argent Endocrinol Metab 51:51-58, 2014 Los autores declaran no poseer conflicto de interés.

Distant metastasis is an infrequent event in patients with differentiated thyroid cancer (DTC) and it occurs approximately in 10 % of cases. Bone is the second metastatic site in patients with DTC. The aim of this multicenter retrospective study was to describe the diagnosis and treatment of bone metas­tases (BMs) in patients followed up in ten different hospitals from Argentina. Diagnosis of BMs was made when: a) BM was confirmed by biopsy, b) a structural bone lesion was found following 131I uptake associated with elevated levels of serum thyroglobulin (Tg) or c) a structural bone lesion was demonstrated by 18FDG uptake on PET/CT, also associated with high levels of serum Tg. Demographical, clinical, pathological and outcome data were obtained from hospital charts. We included 47 patients: 55 % were women, with a median age of 55 years old. Histology of DTC was as follows: 55 % had papillary thyroid cancer, 32 % had follicular thyroid cancer and 13 % had other variants. Diagnosis of BMs were synchronous in 47 % of patients (at the same time as DTC diagnosis) and metachro­nous in 53 %, occurring within a mean period of 72 months after initial diagnosis. In 64 % of patients, BMs were symptomatic: pain was referred in 70 % of these cases. In 68 % of cases, there were multiple sites of BMs, with the spine being the most frequent localization (36 %). In 68 % of patients, other distant metastases were observed, mainly in the lungs. Stimulated Tg levels were known in 38 patients at diagnosis: > 100 ng/ml in 87 % and <100ng/ml in 13 %. Serum calcium level was normal in all subjects in whom it was measured (n = 41). In 9 (29 %) of the 31 patients studied, serum bone turnover markers were elevated. At least one modality of treatment was prescribed in 96 % of patients with BMs. Radioiodine was indicated in 78 % of cases, bisphophonates were prescribed in 64 % of patients, while surgery was performed in 53 %. In 55 % of cases, external beam radiotherapy was also indicated and 23 % of individuals received other therapeutic approaches. Median follow-up was 24 months (range 1-228 months). The survival rate at the end of follow-up was 41 %. One patient (3 %) was considered to have no evidence of disease, 28 patients (59 %) died as a consequence of the DTC. The cause of death was known in 27 cases and it was related to BMs in only 8 patients (30 %). In conclusion, BMs were mainly observed in patients >45 years old, with similar gender distribution. BMs were multiple and had mainly an axial skeletal localization, causing high morbidity in most patients. Although bone turnover markers were elevated in one third of cases, no patient had hypercalcemia. Multiple modali­ties of treatment were used in the majority of cases, which indicates the importance of a multidisciplinary approach. Finally, although BMs were associated with incurable disease, mortality was mainly related to the spread of DTC to other sites, and not specifically to BM. Rev Argent Endocrinol Metab 51:51-58, 2014 No financial conflicts of interest exist.

Consenso intersocietario* sobre tratamiento y seguimiento de pacientes con cáncer diferenciado de tiroides / Inter Society Consensus for the Management of Patients with Differentiated Thyroid Cancer

La incidencia del cáncer diferenciado de tiroides se incrementó exponencialmente en todo el mundo. Aunque estos tumores presentan un pronóstico excelente, se produjeron múltiples cambios en el enfoque terapéutico y de seguimiento en los últimos años. Esta situación, vinculada principalmente con la estadificación por riesgos de recurrencia de la enfermedad, determinó la necesidad de generar un consenso entre representantes de las 3 sociedades argentinas que habitualmente se encuentran involucradas en el manejo de estos pacientes, (Sociedad Argentina de Endocrinología y Metabolismo, Asociación Argentina de Cirugía de Cabeza y Cuello y Asociación Argentina de Biología y Medicina Nuclear). Las recomendaciones se realizaron de acuerdo a la experiencia de los participantes y a la revisión de la literatura. Rev Argent Endocrinol Metab 52:85-118, 2014 Conflictos de interés: Pitoia F: Consultoría, Advisory Board, Speaker Genzyme-Sanofi; Consultoría, Advi­sory Board, Speaker, Steering Committee Bayer; Consultoría, Advisory Board, Speaker Astra Zeneca. Califano I: Speaker Genzyme-Sanofi; Consultoría, Advisory Board, Speaker AstraZeneca. Faure E: Consultoría, Advisory Board, Speaker Genzyme-Sanofi; Consultoría, Advisory Board, Speaker AstraZeneca. Gauna A: Advisory Board Genzyme-Sanofi.; Advisory Board Bayer. Mollerach A: Advisory Board Genzyme-Sanofi. Orlandi A: Advisory Board, Speaker Genzyme-Sanofi. El resto de los autores no declaran conflictos de intereses.

The incidence of differentiated thyroid cancer increased exponentially worldwide. Although these tumors usually have an excellent prognosis, multiple changes occurred in the therapeutic approach and follow-up in recent years. This situation, mainly related to the stratification by the risk of recurrence of the disease, made it necessary to build a consensus among representative members from the three Argentinean societies that are usually involved in the management of these patients, (Argentinean Society of Endocrinology and Metabo lism, Argentinean Association of Head and Neck Surgery and Argentinean Association of Biology and Nuclear Medicine). The recommendations were done according to personal experiences and review of bibliography. Rev Argent Endocrinol Metab 52:85-118, 2014 Conflicts of interest: Pitoia F: Consultancy, Advisory Board, Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker, Steering Committee Bayer; Consultancy, Advisory Board, Speaker AstraZeneca. Califano I: Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker AstraZeneca. Faure E: Consultancy, Advisory Board, Speaker Genzyme-Sanofi; Consultancy, Advisory Board, Speaker AstraZeneca. Gauna A: Advisory Board Genzyme-Sanofi.; Advisory Board Bayer. Mollerach A: Advisory Board Genzyme-Sanofi.Orlandi A: Advisory Board, Speaker Genzyme-Sanofi. No other financial conflicts of interest exist.

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.

Carcinoma medular de tiroides: estudio multicéntrico. Presentación y evolución en 219 pacientes / Medullary Thyroid Carcinoma: Clinical Presentation and Outcome in 219 Patients

Ante la baja frecuencia del carcinoma medular de tiroides (CMT), en el Departamento de Tiroides de SAEM nos propusimos realizar un estudio de cohorte, observacional, retrospectivo y multicéntrico. Se incluyeron 219 pacientes con diagnóstico histológico de CMT. El 65 % fueron mujeres, la edad promedio fue de 39 ± 20 años (1 a 84 años); 44-% de los casos fueron familiares. Las formas de presentación más frecuentes fueron nódulo tiroideo (58 %) y pesquisa genética por antecedente familiar (22 %). Si bien la citología tiroidea fue diagnóstica de CMT en el 39 % de los casos, fue determinante de indicación quirúrgica en el 79 %. En el 47 % de los pacientes el diagnóstico de CMT se obtuvo previamente al tratamiento quirúrgico inicial por punción aspiración con aguja fina (PAAF), estudio genético o nivel de calcitonina (CT)). El 65 % se presentó en estadios avanzados (TNM III y IV). El estudio del protoncogen RET se realizó en 162 pacientes (74 %). En el 49 % se observó mutación siendo la más frecuente (76 %) en el codón 634. La forma hereditaria más frecuentemente observada fue el síndrome de neoplasia endocrina múltiple (NEM) 2A (57 % de los casos familiares), seguida por carcinoma medular familiar (25 %) y NEM 2B (13 %). Los casos familiares tuvieron menor edad al diagnóstico y mayor frecuencia de diagnóstico prequirúrgico. Los casos índice tuvieron mayor edad al momento del diagnóstico, mayores niveles de antígeno carcinoembrionario (CEA) y CT prequirúrgicos, mayor proporción de estadios III y IV y mayor porcentaje de evidencia de enfermedad al momento de la última consulta que aquellos detectados por pesquisa. En 143 pacientes (65 %) se obtuvieron registros completos de seguimiento en los que se analizaron los factores relacionados con la evolución. La mediana de seguimiento fue de 44 meses: fallecieron 21 pacientes (14,6 %) y 122 (86 %) viven; 76 de estos (54 %) se encuentran libres de enfermedad. El grupo con evidencia de enfermedad se presentó en estadios más avanzados. Resultaron factores de mayor riesgo para evidencia de enfermedad: sexo masculino, CMT esporádico, niveles elevados de CT prequirúrgicos, estadio IV y presencia de metástasis. Los niveles de CT posquirúrgicos fueron menores en aquellos pacientes que en la evolución final no presentaron evidencia de enfermedad. El principal factor pronóstico de la evolución de los pacientes con CMT fue el estadio de presentación, determinando la importancia del diagnóstico precoz con el fin de poder implementar un tratamiento quirúrgico curativo en estadios menos avanzados.(AU)

Due to the low frequency of medullary thyroid cancer (MTC), an observational, cohort, retrospective multicenter study was conducted at the Thyroid Department of the Endocrine and Metabolism Argentine Society (SAEM). We included 219 patients with histologically proven MTC, with a mean age of 39 ± 20 yr (range 1-84 years). Sixty five percent were women and 44% were familial cases. The most common presentations were thyroid nodule (58 %) and genetic screening due to family history (22 %). In 39 % of patients, diagnosis of MTC was made by fine needle aspiration, but cytology led to surgery in 79 %. In 47 % of patients, MTC was diagnosed by cytology, calcitonin (CT) levels or genetic studies prior to initial surgery. Sixty five percent of patients had advanced stages of the disease (TNM III or IV) at diagnosis. Proto-oncogene RET was studied in 162 patients (74 %). In 49% a mutation was reported, most frequently in codon 634 (76 %). Regarding hereditary forms of MTC, MEN 2A was the most frequent (57%), followed by familial MTC in 25 % and MEN 2B in 13 % of cases. Familial cases were younger subjects and had more frequently a pre-surgery diagnosis. Index cases were older, with higher CEA and CT levels, presented in more advanced stages and had more frequently evidence of disease at final assessment than patients who were diagnosed by genetic screening. Follow-up records of 143 patients were analyzed (65%); median time was 44 months; 21 patients died (14.6 %) and 122 survived (86 %), 76 showed no evidence of disease (NED) (54 %). High risk factors for evidence of disease at the final evaluation were: male gender, sporadic MTC, higher CT pre-surgery levels, stage IV and metastasis. Post surgery CT levels were lower in patients with NED. Stage at initial diagnosis was the main prognostic factor in patients with MTC, determining the importance of early detection for performing curative surgery in less advanced stages.(AU)

Programa nacional de bocio nodular (PRONBONO): Estudio multicéntrico de bocio nodular único palpable / National Program for Nodular Goiter (PRONBONO): Multicenter study of single palpable thyroid nodules

Introducción: La presencia de nódulos tiroideos palpables en la población general, es uno de los signos clínicos tiroideos más frecuentes en la práctica diaria. Objetivos: 1) establecer la prevalencia de las distintas patologías en bocio nodular único palpable y analizar sus características y su relación con los resultados citológicos. 2) analizar la existencia de diferencias regionales en Argentina. Pacientes y Métodos: Estudio prospectivo de 739 pacientes con bocio nodular único palpable evaluados entre el 1/1/2000 y el 31/12/2001 en Centros de Buenos Aires, Bahía Blanca, Mendoza y La Pampa. Se recabaron datos de examen clínico, ecografía tiroidea, TSH, ATPO y citología por punción con aguja fina. (PAAF). Fue utilizado para el análisis estadístico Correlación de Pearson, X2 y Test de Fisher. Resultados: la edad (X ± DS) fue 46,3 ± 14 años, 93,1 % eran de sexo femenino. El 1,6 % tenía historia de radiación en cuello y el 29,9 % antecedentes familiares de patología tiroidea. Hallazgos clínicos: disfagia en el 7,9 %, disfonía 3,5 %, crecimiento nodular en los últimos 6 meses 19,2 %, consistencia dura el 24,7 %, fijeza a estructuras adyacentes 1,5 % y adenopatías en el 3 %. Hallazgos bioquímicos: TSH normal en el 81,2 % y ATPO positivos en el 30,3 % de los casos. Características Ecográficas: nódulos sólidos: 53,1 %, hipoecoicos: 63,8 %, microcalcificaciones 10,3 %, halo incompleto: 15 %, multinodular: 30,5 %, tiroides heterogénea: 60,2 % y adenopatías: 3,8 %. Hallazgos citológicos: En el 86,8 % de los casos fue necesario solo una punción para llegar al diagnóstico. Insatisfactorio (excluyendo quiste): 3,2 %: benignos: 77,3 %; sospechosos: 12,6 % y cáncer: 7 % (42 papilar, 2 medular y 3 sin especificar). Una correlación significativa (p<0,02) fue observada entre citología maligna y crecimiento rápido, dureza, fijeza a estructuras vecinas, nódulo sólido, halo incompleto y adenopatías aunque estos parámetros son más frecuentes en números absolutos en nódulos benignos. La mayoría de las cirugías fueron indicadas en base al hallazgo citológico. El diagnóstico histológico de los 96 pacientes que fueron operados mostró 51 carcinomas, de los cuales solo dos tenían citología benigna y 31 adenomas. Conclusión: Los nódulos palpables únicos fueron más frecuentes en mujeres eutiroideas en la edad media de la vida. Un tercio tenía historia familiar de patología tiroidea, similar al porcentaje hallado de ATPO positivos. Por ecografía los nódulos fueron predominantemente sólidos, hipoecoicos, únicos con resto de la glándula tiroides heterogénea. La PAAF fue predominantemente benigna. El crecimiento rápido, la dureza, la fijeza a estructuras adyacentes, el halo incompleto y la presencia de adenopatías fueron relacionados con malignidad, pero la benignidad fue más frecuente. En la mayoría de los pacientes la cirugía fue recomendada por los hallazgos citológicos. Nuestros resultados son similares a los reportados en otras áreas geográficas.

Introduction: the presence of palpable thyroid nodules in the general population is one of the most common clinical signs of thyroid disease in daily practice. Objectives: 1) To assess the prevalence of pathologies, clinical and cytological findings of single palpable thyroid nodules (SPTN) in Argentina. 2) Analyze the regional differences in Argentina. Methods: Prospective study of 739 patients with STPN were evaluated at centres in Buenos Aires, Bahía Blanca, Mendoza, and La Pampa between 1/1/00 and 12/31/01. Clinical examination, thyroid ultrasound scan (US), TSH, TPOAb and fine needle aspirations (FNA) were performed. Statistics: Pearson Correlation, X2 & Fisher Tests. Results: Age (X ± SD) 46 ± 14ys: 93.1 % were women. Previous history of neck radiation & familial thyroid disease were found in 1.6 and 29.9 % respectively. Clinical findings: dysphagia: 7.9 %; dysphonia: 3.5%; nodule growth: 19.2 %; hard consistence: 24.7 %; fixation to adjacent structure: 1.5 % and lymphadenopathies (ADP): 3 %. Biochemical findings: TSH was normal in 81.2 % & TPOAb+ in 30.3 %. US features: solid: 53.1 %; hypoechoic: 63.8 %; microcalcifications: 10.3 %; incomplete halo: 15 %; more than 1 nodule: 30.5 %; thyroid heterogeneity: 60.2 % and ADP: 3.8 %. Cytology: Only 1 FNA was needed in 86.8%. Unsatisfactory (excluding cysts): 3.2 %; benign: 77.2%; suspicious: 12.6 % and cancer: 7 % (42 papillary, 2 medullary and 3 non specified). A significant correlation (p<0.02) was established between malignant nodules and rapid growth, hard, fixed, solid nodule, incomplete halo and ADP, though these parameters were more frequent (in absolute number) in benign nodules. Surgery was mainly indicated based on FNA results. Histological diagnosis of 96 patients who underwent surgery showed 51 carcinomas, of which only 2 were cytologically benign and 31 adenomas. Conclusion: Palpable single nodules were more frequent in middle aged euthyroid women. One third had familial thyroid pathology, similar to the presence of TPOAb. On US, nodules were predominantly solid, hypoechoic, single with heterogeneous thyroid gland. FNA was predominantly benign. Rapid growth, hard, fixed, solid nodule, incomplete halo and ADP were associated with malignancy, but benignity was more common. In most of the patients surgery was recommended based on cytological findings. Our results are similar to those reported in other geographic areas.

Utilidad de la Tiroglobulina sérica preablación como predictor de evolución en los pacientes con carcinoma diferenciado de tiroides / Usefulness of preablation serum thyroglobulin as a predictor of the evolution of patients with differentiated thyroid carcinoma

El presente es un trabajo retrospectivo y multicéntrico para evaluar el valor de la Tiroglobulina (Tg) medida preablación como predictor de evolución en 274 pacientes con Carcinoma Diferenciado de Tiroides (CDT). Se incluyeron pacientes con anticuerpos a Tg (TgAb) negativos, tratados con tiroidectomía total, ablación del remanente, con una evolución mayor a 2 años y a los cuales se les midió la Tg bajo estímulo de TSH. Se correlacionó la Tg preablación con el primer control de Tg bajo estímulo de TSH, con el estadio de TNM y con el estado de la enfermedad a Tiempo Final (TF) de seguimiento. Según el TNM, 205 pacientes estuvieron en Estadio 1, 19 en 2, 34 en 3 y 16 en 4. A T F, 172 pacientes estuvieron Libres de Enfermedad (LE), 43 con Enfermedad Dudosa (ED) y 59 con Enfermedad Persistente/Recurrente (EP). Agrupamos la población en rangos de Tg de 0.5-2.0; 2.1-10.0; 10.1-40.0, 40.1-100 y > 100 ng/mL. No hubo asociación significativa entre la Tg preablación y el estadio del TNM en tanto que la correlación con la Tg estimulada se observó solo en los pacientes con Tg < 2.0 ng/mL ya que el 86.7 % se mantuvo en ese rango. El resto de los grupos mostró, en respuesta a la ablación, una disminución de la Tg en porcentajes variables mientras que otros la aumentaron. Relacionando la Tg preablación con el estado de enfermedad a TF observamos que los pacientes con valores =10 ng/mL llegaban en mayor proporción LE al T F. El estadio de TNM mostró correlación con el estado de enfermedad a TF estando LE los de menor riesgo. En pacientes con CDT, los niveles de Tg preablación menores a 10 ng/mL son un marcador de buen pronóstico. Consideramos que la Tg preablación es útil para inferir la probable evolución de los paciente y una herramienta auxiliar para cálculo de riesgo del paciente. Los autores declaran no tener conflictos de interés.

We present a retrospective and multicentric study to evaluate the measurement of preablation Thyroglobulin (Tg) as a predictor of the evolution of 274 patients with DTC. All the patients included in the study had negative TgAb, were treated with total thyroidectomy, ablation of the remnant tissue and an evolution period of more than 2 years. We measured preablation Tg under stimulation with endogenous TSH. We correlated the preablation Tg with that at the first control at LT4 withdrawal, with TNM stratification and the final statement of the disease at Final Time (FT). At the end of the evolution period, patients were classified as: free of disease (n=172), with doubtful disease (n=43) and with persistent disease (n=50). According to their Tg levels, patients were subdivided the following ranges of Tg: 0.5-2.0; 2.1-10.0; 10.1-40.0; 40.1-100 and >100 ng/mL. There was not significant correlation between preablation Tg and TNM stratification. We observed correlation between preablation Tg and the first stimulated Tg =2.0 ng/mL as 86.7 % of the patients persisted in this range while the rest of them either moved to a lower or a higher range in response to the ablation. Considering the relationship between preablation Tg and the state of disease at FT, we found out that most of the patients with preablation Tg <10.0 ng/mL were free of disease. TNM classification correlated with the final state of the disease, with low risk patients having a high probability of being free of disease. In patients with CDT, preablation Tg below =10.0 ng/mL could be a marker of good prognosis. We consider that preablation Tg can be a valuable tool to predict the evolution and risk of patients with CDT. No competing financial interests exist.

Carcinoma en quiste tirogloso / Carcinoma in thyroglosal duct cyst

El carcinoma diferenciado de tiroides en quiste tirogloso (CaQT) es una rara entidad. En diferentes series de pacientes operados por quistes tiroglosos su incidencia fue del 0.7 al 1.07%. Luego de la extirpación del quiste por el procedimiento de Sistrunk, no hay consenso sobre la indicación de tiroidectomía total, radioablación y/o terapéutica supresiva con levotiroxina. El objetivo del Departamento de tiroides de SAEM, fue evaluar: formas de presentación, evolución clínica, métodos diagnósticos de utilidad y tratamiento para consensuar futuras conductas. Material y Métodos: Estudio multicéntrico, retrospectivo en 22 pacientes entre 10 a 69 años, 15 mujeres y 7 varones. Resultados: El tamaño de los quistes osciló entre 1 y 8 cm (Mediana= 3.0 cm, Χ ± DS= 3.7 ± 2.2 cm). La mitad de los pacientes presentó crecimiento del quiste en los 6 meses previos a la cirugía. La punción resultó sospechosa en 2/5 quistes y positiva en uno. La ecografía tiroidea evidenció nódulos en 4/13 casos (30%). Se realizó tiroidectomía en 17/22 pacientes (total: 15 y subtotal: 2). La histología del CaQT demostró carcinoma papilar en 21 y carcinoma folicular en uno. Hubo coexistencia de cáncer intratiroideo en el 23.5% de los casos, ninguno multicéntrico. Dos pacientes presentaron metástasis ganglionares y otro tuvo compromiso muscular (ninguno de ellos coexistió con cáncer intratiroideo). Se radioablacionó a 13 pacientes. En 9/11 pacientes la tiroglobulina permaneció indetectable durante el seguimiento (1 a 14 años). Conclusiones: 1) Realizar ecografía de cuello y punción ecoguiada a todo paciente con quiste tirogloso. 2) En caso de CaQT combinar simultáneamente tiroidectomía total y procedimiento de Sistrunk. 3) Evaluar radioablación complementaria y tratamiento supresivo con levotiroxina en cada caso. 4) Efectuar el seguimiento tal como en los carcinomas ortotópicos.

Differentiated thyroid carcinoma (DTC) in thyroglosal duct cyst (TGDC) is rare, ranging from 0.7 to 1.07% in different series. After the surgery of choice (Sistrunk procedure) the other alternative treatments such as thyroidectomy (Tx), radioiodine and L-T4 therapy are controversial. OBJECTIVE: to evaluate several and controversial aspects in the largest series of DTC in TGDC reported in the literature. Subjects and methods: retrospective multicentric study: n= 22, aged 10-69 yrs. (15 females and 7 men) who underwent the Sistrunk procedure for TGDC. Results: none of the TGDC was less than 1 cm (median 3.0 cm, Χ±SD= 3.7 ± 2.2cm). In half of them there was an increased cystic size in the last 6 months before surgery. Cyst FNA was suspicious in 2/5 and positive in one, whereas the histological diagnosis of the operated TGCD was papillary cancer in 21 and 1 follicular carcinoma. Thyroid ultrasound (US) (n=13) showed nodules in 30% of the cases. Tx was performed in 17/22 (total: 15, subtotal: 2). Thyroid DTC coexisted in 4/17 (23.5%), and was unilateral in all of them. Lymph node metastases were present in 2 adults and muscle involvement was found in the 10-year old girl. None of these 3 patients had overt thyroid lesions. 131-I therapy was performed in 10 patients. In 9 out of 11 subjects Tg remained undetectable during follow-up (1-14yrs.). Persistent high Tg was present in one case without thyroid DTC. Conclusions: 1) Ultrasonography and FNAB should be performed to every patient with thyroglossal duct cyst 2) In case of TGDC, total Tx and Sistrunk's procedure should be simultaneously combined 3) 131-I therapy and L-T4 suppressive treatment should be evaluated in every case 4) Follow-up as in the DTC.

Cellular organization and appearance of differentiated structures in developing stages of the parasitic platyhelminth Echinococcus granulosus.

Echinococcus granulosus is the causative agent of hydatidosis, a major zoonoses that affects humans and herbivorous domestic animals. The disease is caused by the pressure exerted on viscera by hydatid cysts that are formed upon ingestion of E. granulosus eggs excreted by canine. Protoscoleces, larval forms infective to canine, develop asynchronously and clonally from the germinal layer (GL) of hydatid cysts. In this report, we describe the cellular organization and the appearance of differentiated structures both in nascent buds and developed protoscoleces attached to the GL. Early protoscolex morphogenesis is a highly complex and dynamic process starting from the constitution of a foramen in the early bud, around which nuclei are distributed mainly at the lateral and apical regions. Similarly, distribution of nuclei in mature protoscoleces is not homogenous but underlies three cellular territories: the suckers, the rostellar pad, and the body, that surrounds the foramen. Several nuclei are associated to calcareous corpuscles (Cc), differentiated structures that are absent in the earlier bud stages. The number of nuclei is similar from the grown, elongated bud stage to the mature protoscolex attached to the GL, strongly suggesting that there is no significant cellular proliferation during final protoscolex development. The amount of DNA per nucleus is in the same range to the one described for most other platyhelminthes. Our results point to a sequential series of events involving cell proliferation, spatial cell organization, and differentiation, starting in early buds at the GL of fertile hydatid cysts leading to mature protoscoleces infective to canine.

Histometry of the placental structures involved in the respiratory interchange.

Employing a stereometric technique, we determined the following parameters in six normal term placentae: respiratory area (total surface area of vasculo-syncytial membranes); total villous surface area; proportion of respiratory area (percentage fraction of villous surface that corresponds to the respiratory area). The value of each of these parameters was studied in each placental sample, as well as their distribution in the different placental zones, considered according to their distance from the placental rim. All parameters were distributed heterogeneously throughout the peripheral, intermediate and central zones of the placentae studied. The same parameters were also measured along the full thickness of the placenta, considering subchorial, middle and basal levels. All parameters were homogeneously distributed along the thickness of the placenta. We discuss the functional implications of our findings. Villous surface area values ranged from 8.6 to 13.3 m2 (mean = 10.9 m2). Respiratory areas ranged from 0.97 to 2.43 m2 (mean = 1.57 m2). Between 1:10 and 1:5 of the villous surface area corresponded to the respiratory area.