María D. Balsalobre

Results of surgery for toxic multinodular goiter

PurposeWe analyzed the clinical and histological features of patients operated on for toxic multinodular goiter (TMG) to determine the clinical profile and evaluate the surgical results.MethodsWe reviewed 672 patients who underwent surgery for multinodular goiter (MG), 112 (17%) of whom had hyperthyroidism, and analyzed the epidemiological, clinical, and surgical variables.ResultsThe patients with TMG tended to be older than those with nontoxic MG, with a greater evolution time of the goiter and a higher rate of positive antithyroid antibodies. In the multivariate analysis, the only feature characteristic of TMG, as opposed to nontoxic MG, was the evolution time. Morbidity was 34%, representative of the fact that that most of the patients were seen before the establishment of our endocrine surgical unit. The hyperthyroid symptoms resolved in all patients, but 4 of 17 patients who underwent partial surgical resection showed signs of relapse within a follow-up period of 98 ± 71 months.ConclusionsTMG is characterized by a long evolution time and is most effectively treated by total thyroidectomy, which achieves complete remission from symptoms, without relapse, and is necessary if there is associated carcinoma. However, the incidence of complications may be high if this procedure is not carried out by surgeons with experience in endocrine surgery.

Prophylactic thyroidectomy in MEN 2A syndrome: experience in a single center

BACKGROUND Genetic study of the RET proto-oncogene has modified the management, treatment, and prognosis of medullary thyroid carcinoma (MTC), multiple endocrine neoplasia 2A (MEN 2A), for patients with less advanced tumor stages. Classically, the diagnosis was based on an increase in basal and poststimulus peak calcitonin (bCT and pCT). Prophylactic thyroidectomy, based on results of genetic testing, may reduce recurrences in MTC. STUDY DESIGN Of 82 MTC (MEN 2A) patients genetically diagnosed and surgically treated at our center, 22 received a prophylactic thyroidectomy (RET +, bCT and pCT with normal values and asymptomatic). We analyzed age, gender, phenotype, RET mutation, cervical ultrasound, laboratory tests (bCT, pCT, and CEA), surgery, histologic data, TNM, and followup. RESULTS The 22 patients belonged to 8 families with MTC (MEN 2A). Mean age was 15.2 years (range 5 to 36 years). The RET mutation in 21 patients was Cys-->Tyr and in the remaining patient both in codon 634 in exon 11. The median values of bCT and pCT were 38 pg/mL (range < 15 to 75 pg/mL) and 148.5 pg/mL (range < 15 to 250 pg/mL), respectively. Total thyroidectomy was performed in 8 patients (age < or = 10 years) and associated central neck dissection in 14 patients (age> 10 years). Histologic study showed 7 C-cell hyperplasias and 15 MTCs (8 bilateral); the median size was 0.2 cm (range < 0.1 to 0.7cm); 1 patient had metastatic adenopathies. According to TNM, 7 were stage 0, 14 were stage I, and 1 was stage III. Postsurgery bCT and pCT values were normal in all patients, with a curative rate of 100%. MTC patients compared with C-cell hyperplasia patients were older on average, had higher mean bCT, mean pCT, and mean CEA. CONCLUSIONS Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease and decreases recurrence rates. pCT values above the upper limit of normal may be markers for the presence of MTC and should be considered in selecting operative procedures for these patients.

The value of various definitions of intrathoracic goiter for predicting intra-operative and postoperative complications

BACKGROUND Intrathoracic goiter (IG) is a pathologic and clinical entity defined by criteria that varies from one series to the next. The objective of this study was to determine the most useful definition of IG for predicting intra-operative and postoperative complications. METHODS The study included 201 patients treated for multinodular goiter who met the following criteria: (1) they had no previous thyroid surgery; (2) they had undergone total thyroidectomy; and (3) they were diagnosed with IG according to 1 of the following definitions: (1) clinical; (2) Hsus; (3) Kochers; (4) Torres; (5) Eschapases; (6) Laheys; (7) Lindskogs; (8) Criles; (9) Katlics; and (10) subcarinal. Three variables were evaluated: (1) intra-operative complications; (2) need for a sternotomy; and (3) postoperative complications. RESULTS During orotracheal intubation, there were difficulties in 25 cases, all of which were detected using the 6 least restrictive definitions of IG (these range from the clinical definition to Laheys definition. In 6 (3%) cases, it was necessary to carry out a sternotomy. The thoracic approach could be predicted using Katlics definition. None of the definitions of IG was useful for predicting postoperative complications. CONCLUSION Most definitions of IG can be ignored because they are not clinically relevant. The 6 least restrictive definitions overlap in their utility to predict intubation difficult during the anesthetic process; consequently, the clinical definition should be used because it is the simplest to calculate. Katlics definition is the most useful for predicting a possible sternotomy for extirpating goiter.

Estudio multivariable de los factores de riesgo para desarrollar complicaciones en la cirugía del bocio multinodular

Introduccion. El bocio multinodular (BM) supone un alto volumen de pacientes en los servicios de cirugia endocrina. Sin embargo, los factores de riesgo de morbilidad tras la cirugia no han sido investigados sistematicamente. El objetivo es analizar, mediante un analisis estadistico multivariable, los resultados quirurgicos, en cuanto a morbimortalidad, para poder determinar los factores de riesgo de la cirugia del BM. Pacientes y metodo. Se han revisado retrospectivamente 672 BM intervenidos. Las variables analizadas fueron la edad, el sexo, la cirugia previa, el tiempo de evolucion, la sintomatologia, el componente intratoracico, la gradacion cervical del bocio, la duracion de la cirugia, la experiencia del cirujano, la tecnica quirurgica, la identificacion de estructuras, el carcinoma tiroideo asociado y el peso de la pieza tiroidea. Se aplicaron el test de la c2 y el de la t de Student, asi como un analisis de regresion logistica. Resultados. El indice de morbilidad fue del 22% (n = 147), la mayoria correspondiente a hipoparatiroidismos y lesiones recurrenciales transitorias. Los factores de riesgo para desarrollar estas complicaciones fueron la presencia de sintomatologia (p = 0,0131), el hipertiroidismo (p = 0,0333), la sintomatologia compresiva (p = 0,0158), la gradacion clinica del bocio (p = 0,0482), la tecnica quirurgica realizada (p < 0,00001) y el peso del tiroides (p = 0,0302); como factores de riesgo independiente persistieron la tecnica quirurgica, el hipertiroidismo y la gradacion del bocio. El indice de complicaciones definitivas fue del 2,2% (n = 15), que corresponden a 6 hipoparatiroidismos (0,9%) y 10 lesiones recurrenciales (1,5%). El factor de riesgo para su desarrollo es el hipertiroidismo (p = 0,0037; riesgo relativo [RR] = 2,8). Conclusiones. El principal factor de riesgo independiente para el desarrollo de complicaciones en la cirugia del BM es el hipertiroidismo.

Results of surgical treatment in multinodular goiter with an intrathoracic component

Purpose(1) To determine the clinical profile of intrathoracic multinodular goiter (IMG); (2) to evaluate the results of surgery, and (3) to analyze the incidence of malignancy and its evolution.MethodsTwo hundred and forty-seven operated cases of IMG were reviewed. These cases of IMG had all been diagnosed according to Eschapse’s definition (>3cm below the sternal manubrium). The morbidity and postoperative evolution were analyzed. A comparative study was carried out on a group of 425 cases of nonintrathoracic goiter. We applied the χ2 test, Student’s t-test, and a logistical regression analysis.ResultsIntrathoracic MG occurs in patients over 60 years of age, with goiter which has a long evolution time (>12 years), and more than 60% are symptomatic. Oral tracheal intubation was difficult in 10% (n = 24) of the cases, and 7 required the use of a fibrobronchoscope. In 8 cases (3%) a thoracic approach was necessary. Morbidity occurred in 24% (n = 59), most notably 29 recurring lesions (12%), of which 2 were definitive (0.8%), and 31 hypoparathyroidisms (13%), of which 1 was definitive (0.4%). No significant difference was found in the postsurgical morbidity between the intrathoracic MG and the nonintrathoracic cases. Regarding the remission of the symptoms, the results were excellent. In 14 cases (5.7%) thyroid carcinoma was related with, most of these being papillary microcarcinoma. In 10 of the 49 cases of partial surgery (20%) a relapse of the goiter was observed.ConclusionsIntrathoracic MG is usually asymptomatic and it occurs in goiter with a long time of evolution. Surgery is a good therapeutic option given that the goiter can be removed via the neck, with low morbidity, a remission of the symptoms, malignancy is ruled out, and recurrence can be avoided if a total thyroidectomy is performed.

Presurgical assessment of the tumor burden of familial medullary thyroid carcinoma by calcitonin testing

BACKGROUND Early diagnosis of familial medullary thyroid carcinoma (MTC) is currently done by genetic analysis. These techniques have replaced calcitonin stimulation testing, which was previously used for this purpose. Some studies suggest a relationship between MTC spread and calcitonin levels. The aim of this study was to assess whether the tumor burden of MTC associated with multiple endocrine neoplasia type 2A (MEN 2A) syndrome can be estimated from the plasma calcitonin values before surgery. STUDY DESIGN We retrospectively studied the relationship of basal and peak calcitonin values before thyroidectomy with histopathologic findings in 53 patients with MEN 2A syndrome from 14 families. The MTC was classified according to TNM staging. Analysis of variance was used for statistical analysis complemented with equality contrasts for pairs of means by the least significant difference method with a Students t-test and with the Bonferronis adjustment. RESULTS A positive association was found between tumor stage and basal and peak calcitonin levels. There were significant differences between the following: mean basal concentrations of patients with C cell hyperplasia (CCH) (34.3 pg/mL) and TNM stage II (1,097.4 pg/mL), p < 0.01; CCH and TNM stage III (2,940.8 pg/mL), p < 0.001; TNM stage I (165.3 pg/mL) and stage II (1,097.4 pg/mL), p < 0.01, and between TNM stages I and III, p < 0.001. Poststimulation mean concentrations were different between CCH (48.7 pg/mL) and TNM I (514.2 pg/mL), p < 0.001. CONCLUSIONS Preoperative calcitonin testing may be useful for assessing tumor spread and should be considered when deciding the extent of surgery for MEN 2A MTC.

Resultados del tratamiento quirúrgico en 247 pacientes con bocio multinodular con componente intratorácico

Resumen Objetivos a) Determinar el perfil clinico de los bocios multinodulares intratoracicos; b) valorar los resultados de la cirugia, y c) analizar la incidencia de malignidad y su evolucion. Pacientes y metodo Se revisan 247 bocios multinodulares intratoracicos, segun la definificion de Eschapase (≥ 3 cm por debajo del manubrio esternal), operados. Se analiza la morbilidad y la evolucion postoperatoria. Se realiza un estudio comparativo con un grupo de 425 bocios multinodulares no intratoracicos. Se aplican los tests de la χ2, de la t de Student y de regresion logistica. Resultados El bocio multinodular intratoracico se presenta en pacientes con mas de 60 anos de edad y con un bocio de larga evolucion (> 12 anos); mas del 60% presenta manifestaciones clinicas. Hubo dificultades en la intubacion orotraqueal en el 10% (n = 24) de los casos, y en 7 de ellos fue preciso utilizar el fibrobroncoscopio. En 8 casos (3%) hubo que realizar un abordaje toracico. La morbilidad fue del 24% (n = 59) y destacan 29 lesiones recurrenciales (12%), 2 definitivas (0,8%) y 31 hipoparatiroidismos (13%), 1 de ellos definitivo (0,4%). No se han obtenido diferencias significativas en la morbilidad posquirurgica entre los bocios multinodulares intratoracicos y los no intratoracicos. Los resultados en cuanto a la remision de la sintomatologia fueron excelentes. En 14 casos (5,7%) se asociaba un carcinoma tiroideo, la mayoria microcarcinomas papilares. En diez de las 49 cirugias parciales (20%), el bocio recidivo. Conclusiones El bocio multinodular intratoracico suele ser sintomatico y se presenta en bocios de larga evolucion. La cirugia es una buena opcion terapeutica, ya que el bocio se puede extirpar por via cervical con una baja morbilidad, con lo que remite la sintomatologia, se descarta su posible malignidad y, si se realiza una tiroidectomia total, se evitan las recurrencias.

Metástasis a distancia como forma de inicio de un carcinoma folicular de tiroides

Sr. Director: El cáncer diferenciado de tiroides es la enfermedad tumoral tiroidea más frecuente y tiene un excelente pronóstico, con larga supervivencia a largo plazo. De las 2 variantes, papilar y folicular, esta última es más infrecuente y agresiva. En la mayoría de los casos el tumor está localizado en el tiroides o, como mucho, con afección local; son infrecuentes las metástasis a distancia. Cuando éstas ocurren, aparecen durante la evolución de dicho tumor, y son excepcionales como inicio del cuadro1. Por ello, presentamos 2 casos de carcinomas foliculares diagnosticados como consecuencia de la detección de una metástasis a distancia. Caso 1: varón de 59 años, sin antecedentes de interés, que consultó por tumoración en el glúteo derecho de 1 año de evolución. A la exploración se objetiva una tumoración sin signos inflamatorios, hipervascularizada y con latido a la palpación. La tomografía computarizada (TC) mostró una gran tumoración glútea derecha con afección de sacro y pala ilíaca, y en la arteriografía se observó que la vascularización dependía de la arteria hipogástrica derecha (fig. 1A). Se realizó una biopsia que informó de metástasis de carcinoma folicular de tiroides. La gammagrafía con difosfo-99Tc mostró acumulaciones focales patológicas en la articulación coxofemoral y la cresta ilíaca derecha. En la zona cervical se objetivó un nódulo tiroideo derecho, el cual se puncionó e informó de sospecha de carcinoma folicular. Se intervino al paciente mediante tiroidectomía total bilateral y vaciamiento ganglionar yugular. La masa glútea se consideró irresecable dada la afección ósea y su vascularización. La histología mostró un carcinoma folicular de 4 × 2 cm con un nódulo satélite de 0,3 cm. Se administraron 200 mCi de 131I como tratamiento adyuvante y radioterapia en el área glútea (30 Gy). Al año y medio presentó metástasis en la vértebra dorsal VIII y IX, con rastreo cervical normal, y se lo trató con radioterapia dorsal hasta completar los 30 Gy. La evolución fue lenta; a los 4,5 años presentó síndrome de compresión medular, y falleció por evolución de la enfermedad 6 meses después. Caso 2: mujer de 68 años, sin antecedentes médicoquirúrgicos de interés, que ingresó por fractura patológica de cabeza de fémur (fig. 1B). El análisis inicial no objetivó ninguna causa de la fractura; fue intervenida por el servicio de traumatología que le colocó una prótesis de cadera. El estudio histológico de la pieza ósea remitida fue de metástasis ósea de carcinoma folicular de tiroides. El estudio tiroideo mostró un nódulo izquierdo de 3 cm de diámetro, y el estudio de extensión mostró metástasis pulmonares bilaterales, hepáticas bilaterales y óseas (pelvis y vértebras en diferentes áreas), y adenopatías mediastínicas y retroperitoneales. Se realizó una tiroidectomía total bilateral con vaciamiento ganglionar central y yugulolateral bilateral y luego se administró yodoterapia con 131I a altas dosis (200 mCi). La histología confirmó un carcinoma folicular. La evolución fue tórpida, con deterioro progresivo, y falleció a los 4 meses de la intervención. Las metástasis a distancia1 en el carcinoma folicular se presentan en el 10-15% de los casos y se localizan, sobre todo, en áreas pulmonar y ósea; son menos frecuentes los cerebrales, hepáticos y cutáneos. La mayo-

Perfil histológico e inmuno-histoquímico del carcinoma medular de tiroides esporádico y familiar

INTRODUCTION The histological and immunohistochemical profile of medullary thyroid carcinoma is ill-defined. The objective of this study was to determine the epidemiological, histological, and immunohistochemical characteristics of medullary carcinoma and to analyze whether differences exist between sporadic and familial carcinomas. PATIENTS AND METHODS Fifty-five histologically confirmed tumors were studied. Histological slides were reviewed and immunohistochemical staining of the archival paraffin blocks was performed. RESULTS Nineteen of the 55 carcinomas (35%) were sporadic, and 36 (65%) familial. Sex distribution was similar, but familial carcinoma was more common in patients under 40 years of age (p<0.001). A solid growth pattern and plasmacytoid cells were found in most cases. C-cell hyperplasia and multicentricity were more frequent findings in familial carcinoma, while tumor necrosis, hemorrhagic foci, vascular invasion, and neovascularization were more common in the sporadic type. Immunohistochemical staining was positive for calcitonin, CEA, bcl-2, and p53 protein. With regard to staging, familial carcinomas were diagnosed in the earliest stages, when they were smaller and there were no lymph node metastases (p<0.01). CONCLUSIONS Familial cases were more frequent when there was more C-cell hyperplasia and multicentricity. Sporadic cases more frequently showed foci of necrosis, hemorrhage, vascular invasion, and neovascularization. Neither histopathological nor immunohistochemical criteria are useful for differentiating between familial and sporadic forms.

Valoración espirométrica de la afectación respiratoria en el bocio multinodular asintomático con componente intratorácico

La obstruccion de la via aerea se infravalora en el bocio intratoracico asintomatico. Nuestro objetivo ha sido valorar mediante espirometria la afectacion de la via aerea superior y la repercusion en la funcion respiratoria de pacientes asintomaticos con bocio multinodular intratoracico. Para ello se selecciono prospectivamente a 21 pacientes con bocio intratoracico asintomatico a quienes se habia practicado una tiroidectomia. Se realizo la espirometria en decubito supino y en bipedestacion antes y a los 3 meses de la cirugia. El estudio preoperatorio mostro en decubito una afectacion obstructiva leve en 4 casos (20%), en 2 de los cuales persistia en bipedestacion (10%). Tras la cirugia se normalizo la alteracion en los 4 casos. En conclusion, la espirometria en el bocio intratoracico asintomatico muestra una afectacion obstructiva leve de la funcion respiratoria en el 10-20% de los casos, en funcion de la postura. La cirugia se acompana de la normalizacion de los parametros alterados y de la mejoria del resto. Estos datos apoyan la necesidad de indicar la cirugia lo antes posible.