Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial.

BACKGROUND: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. METHODS: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. CONCLUSIONS: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03980132.

Usefulness of the Wisconsin and CaPTHUS indices for predicting multiglandular disease in patients with primary hyperparathyroidism in a southern European population.

BACKGROUND: Focused parathyroidectomy is a safe technique for the treatment of primary hyperparathyroidism. The CaPTHUS score and the Wisconsin index are preoperative diagnostic tools designed to distinguish between single- and multigland disease. The aim of the study is to evaluate the usefulness of these models for predicting multiglandular disease in a European population. METHODS: Retrospective review of a database of patients operated upon for primary hyperparathyroidism at a referral center. The sensitivity, specificity, positive and negative predictive values, and reliability of both scores for the prediction of multiglandular disease, were calculated. Receiver operating characteristic (ROC) curves were constructed to assess the sensitivity and specificity of CaPTHUS score and Wisconsin Index for predicting single-gland disease. A level of P<0.05 was accepted as significant. RESULTS: Two hundred and eighty-one patients who underwent successful surgery from January 2001 to December 2018 were included. Single-gland disease was detected in 92.5%, and 73.7% had a CaPTHUS score of ≥3. The sensitivity, specificity, positive and negative predictive values of this model for predicting single-gland disease with a score of ≥3 were 76.9%, 66.7%, 96.6%, and 18.9% respectively. The area under the curve value of the CaPTHUS score for predicting single-gland disease was 0.74. A Wisconsin Index >2,000 and an excised gland weight above one gram presented a positive predictive value for single-gland disease of 92.5%. CONCLUSIONS: Despite the good performance of both scales, the established cut-off points did not definitively rule out parathyroid multiglandular disease in our population. In cases with a minimal suspicion of this condition, additional intraoperative techniques must be used, or bilateral neck explorations should be performed.

Development and validation of a new model for predicting hypocalcaemia after total thyroidectomy: the NuGra model.

BACKGROUND: Hypocalcaemia is the most frequent complication after total thyroidectomy. Finding a method for its early detection has become a priority. A single-center prospective cohort study was conducted to identify risk factors for postoperative hypocalcaemia, develop an early detection model, and test its validity in a different group of patients. METHODS: The sample was composed of patients who underwent a total thyroidectomy between May 2012 and September 2015. Demographic, clinical, laboratory, and surgical data were collected. The incidence of hypocalcaemia and permanent hypoparathyroidism was calculated. Bivariate and multivariate analysis identified several independent predictors of hypocalcaemia, which were used to design a predictive model. The validity of the model was subsequently tested in a different cohort. Area under the ROC curve (AUROC) was calculated to determine its predictive power. RESULTS: The study and validation groups included 352 and 118 patients, respectively. Seventy-three patients developed laboratory-confirmed hypocalcaemia (20.7%), and symptomatic in 43 (12.2%). Multivariate analysis confirmed as independent predictors of hypocalcaemia the higher number of parathyroid glands identified [OR 1.41(0.98, 2.02); p = 0.063] and pre-to-postoperative gradient of parathormone decline [OR 1.06(1.04, 1.08); p < 0.001]. Based on these variables, the NuGra (Number of parathyroid glands identified-Gradient of decline) model was developed for predicting laboratory-confirmed hypocalcaemia. Its predictive power was high (AUROC 0.902, CI 0.857-0.947) for the study and the validation group (AUROC 0.956, CI 0.919-0.993). CONCLUSIONS: A higher number of parathyroid glands identified and a higher gradient of parathormone decline are risk factors for post-thyroidectomy hypocalcaemia. The NuGra model is useful for early prediction of individual risk for hypocalcaemia.

Profilaxis del tromboembolismo venoso en cirugía general en España. Análisis de una encuesta nacional / Prophylaxis of venous thromboembolism in general surgery in Spain. Analysis of a national survey

INTRODUCCIÓN: El tromboembolismo venoso (TEV) representa una complicación postoperatoria grave, pero evitable con una profilaxis adecuada. Las encuestas aportan información útil acerca de las actitudes y preferencias respecto a la prevención del TEV. MÉTODOS: Estudio transversal descriptivo, basado en una encuesta, remitida a los cirujanos generales miembros de la Asociación Española de Cirujanos (AEC), y que incluye 31 preguntas acerca del TEV postoperatorio y su prevención, así como 3 casos clínicos. RESULTADOS: La encuesta fue contestada por 530 cirujanos, lo que representa el 21,8% de los 2.429 miembros invitados a participar por correo electrónico. La mayoría de los cirujanos participantes trabajan en hospitales docentes grandes, siendo el 28,5% médicos residentes. Para el 28% el TEV representa un problema importante. Aunque el 81% considera que tiene un conocimiento adecuado sobre la prevención del TEV postoperatorio, un porcentaje similar reconoce necesitar más formación. La mayoría (98,7%) utiliza las heparinas de bajo peso molecular, consideradas la modalidad más eficaz y segura, seguida de los métodos mecánicos. El método de estratificación de riesgo más utilizado es el de Caprini (81%). La mayoría comienza la profilaxis farmacológica preoperatoriamente, pero existe bastante variación en las dosis utilizadas, así como en las pautas de inicio y duración, sobre todo en cirugía no oncológica. CONCLUSIONES: Existe interés y, en general, un adecuado conocimiento acerca de la prevención del TEV entre los cirujanos españoles. Sin embargo, creemos necesaria mayor formación sobre aspectos prácticos de la profilaxis, adaptando las recomendaciones de las guías recientes a protocolos locales

INTRODUCTION: Venous thromboembolism (VTE) represents a serious postoperative complication that can be prevented by adequate thromboprophylaxis. Surveys provide relevant information about clinician's attitudes and preferences regarding VTE prophylaxis. METHODS: Transversal, descriptive study based on a survey sent to general surgeons members of the Spanish Association of Surgeons (AEC), that included 31 questions regarding postoperative VTE and its prevention, as well as three clinical scenarios. RESULTS: 530 surgeons, 21.8% of the 2,429 invited by electronic mail to participate, completed the survey. Most of the answering clinicians work on in big teaching hospitals, and 28.5% are residents. VTE represents a serious problem for 28% of participants. Although 81% consider that their knowledge on the prevention of postoperative VTE is adequate, a similar percentage recognizes the need for further education. The vast majority (98.7%) use low molecular weight heparins, which are considered the most effective and safe modality, followed by mechanical methods. The Caprini risk assessment score is used by 81% of surgeons, who usually start pharmacological prophylaxis preoperatively. However, there are remarkable differences in the dosing of heparins, timing of initiation, and duration, especially in non-oncologic surgical patients. CONCLUSIONS: Most Spanish surgeons are interested in the prevention of postoperative VTE. Overall, the level of knowledge on thromboprophylaxis is adequate. However, our results indicate that there is a need for better education on relevant practical aspects of prophylaxis that could be achieved by incorporating recommendations from recent guidelines to local hospital-based protocols

Prophylaxis of venous thromboembolism in general surgery in Spain. Analysis of a national survey. / Profilaxis del tromboembolismo venoso en cirugía general en España. Análisis de una encuesta nacional.

INTRODUCTION: Venous thromboembolism (VTE) represents a serious postoperative complication that can be prevented by adequate thromboprophylaxis. Surveys provide relevant information about clinician's attitudes and preferences regarding VTE prophylaxis. METHODS: Transversal, descriptive study based on a survey sent to general surgeons members of the Spanish Association of Surgeons (AEC), that included 31 questions regarding postoperative VTE and its prevention, as well as three clinical scenarios. RESULTS: 530 surgeons, 21.8% of the 2,429 invited by electronic mail to participate, completed the survey. Most of the answering clinicians work on in big teaching hospitals, and 28.5% are residents. VTE represents a serious problem for 28% of participants. Although 81% consider that their knowledge on the prevention of postoperative VTE is adequate, a similar percentage recognizes the need for further education. The vast majority (98.7%) use low molecular weight heparins, which are considered the most effective and safe modality, followed by mechanical methods. The Caprini risk assessment score is used by 81% of surgeons, who usually start pharmacological prophylaxis preoperatively. However, there are remarkable differences in the dosing of heparins, timing of initiation, and duration, especially in non-oncologic surgical patients. CONCLUSIONS: Most Spanish surgeons are interested in the prevention of postoperative VTE. Overall, the level of knowledge on thromboprophylaxis is adequate. However, our results indicate that there is a need for better education on relevant practical aspects of prophylaxis that could be achieved by incorporating recommendations from recent guidelines to local hospital-based protocols.

Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management.

BACKGROUND: To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management. METHODS: From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared. RESULTS: Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease. CONCLUSION: Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

Presencia de la mutación BRAF T1799A en el tumor primario como indicador de riesgo, recidiva o persistencia de carcinoma papilar de tiroides / BRAF T1799. A mutation in the primary tumor as a marker of risk, recurrence, or persistence of papillary thyroid carcinoma

Antecedentes y objetivo. La mutación BRAFT1799A se ha relacionado con características tumorales de más agresividad, recidiva tumoral y persistencia de carcinoma papilar de tiroides (CPT), aunque no todos los estudios apoyan esta asociación. En éste, se analiza la asociación entre la presencia de la mutación BRAFT1799A en el tumor primario de pacientes con CPT y las características clinicopatológicas de riesgo, recidiva y persistencia tumoral. Pacientes, material y método. Hemos seguido a 97 pacientes intervenidos de CPT durante una mediana de 64,1 meses. La mutación BRAFT1799A se determinó en ácido desoxirribonucleico procedente de muestras de la tiroidectomía inicial mediante amplificación por PCR del exón 15 del gen braf y análisis de los fragmentos de restricción con la enzima TspRI. Los casos positivos fueron confirmados por secuenciación. La asociación estadística entre la mutación BRAFT1799A y las diferentes variables se estudió mediante los correspondientes tests de contraste de hipótesis más regresión logística. Resultados. El 46,4% de los pacientes eran positivos para la mutación BRAFT1799A. Tras análisis bivariante y multivariante, la mutación BRAFT1799A sólo se asociaba con edad superior a 60 años (odds ratio [OR] = 5,5; intervalo de confianza [IC] del 95%, 1,4-21,9; p=0,019) y tamaño de 1cm o superior (OR=3,6; IC del 95%, 1,2-10,3; p=0,016). No se asociaba con subtipos histológicos, metástasis, recidiva, necesidad de nuevos tratamientos ablativos con I131 o de otras intervenciones quirúrgicas debidas a la aparición de metástasis o persistencia de enfermedad al final del seguimiento. Conclusiones. La mutación BRAFT1799A está asociada a edad superior a 60 años y tamaño tumoral de 1cm o mayor, pero no con otras características clinicopatológicas, recidiva tumoral o persistencia de enfermedad (AU)

Background and objective. The BRAFT1799A mutation is reported to be associated to aggressive, persistent, and recurrent tumor in papillary thyroid carcinoma (PTC) patients. Association of the BRAFT1799A mutation in the primary tumor with the clinicopathological characteristics of PTC patients was analyzed. Patients, material and methods. Ninety-seven PTC patients were followed up for a median of 64.1 months. The BRAFT1799A mutation was analyzed in DNA from initial thyroidectomy biopsies by PCR amplification and restriction fragment length polymorphism using TspRI enzyme. Positive cases were confirmed by DNA sequencing. Statistical association between BRAFT1799A mutation and clinicopathological characteristics was analyzed by the relevant hypothesis tests and logistic regression. Results. 46.4% of patients were positive for the BRAFT1799A mutation. Bivariate and multivariate analysis showed the BRAFT1799A mutation to be only associated to age over 60 years (odds ratio [OR] = 5.5; 95% confidence interval [CI],1.4-21.9; p=0.019) and to tumor size of 1cm or greater (OR=3.6, 95% CI, 1.2-10.3; p=0.016). The BRAFT1799A mutation was not associated to histological subtype, metastasis, recurrence, more aggressive treatments (ablative I131 therapy or surgery), or PTC persistence at the end of follow-up. Conclusions. The BRAFT1799A mutation is associated to age over 60 and a tumor size of 1cm or greater, but not to other clinicopathological characteristics, tumor recurrence or PTC persistence (AU)

[BRAF(T1799A) mutation in the primary tumor as a marker of risk, recurrence, or persistence of papillary thyroid carcinoma]. / Presencia de la mutación BRAF(T1799A) en el tumor primario como indicador de riesgo, recidiva o persistencia de carcinoma papilar de tiroides.

BACKGROUND AND OBJECTIVE: The BRAF(T1799A) mutation is reported to be associated to aggressive, persistent, and recurrent tumor in papillary thyroid carcinoma (PTC) patients. Association of the BRAF(T1799A) mutation in the primary tumor with the clinicopathological characteristics of PTC patients was analyzed. PATIENTS, MATERIAL AND METHODS: Ninety-seven PTC patients were followed up for a median of 64.1 months. The BRAF(T1799A) mutation was analyzed in DNA from initial thyroidectomy biopsies by PCR amplification and restriction fragment length polymorphism using TspRI enzyme. Positive cases were confirmed by DNA sequencing. Statistical association between BRAF(T1799A) mutation and clinicopathological characteristics was analyzed by the relevant hypothesis tests and logistic regression. RESULTS: 46.4% of patients were positive for the BRAF(T1799A) mutation. Bivariate and multivariate analysis showed the BRAF(T1799A) mutation to be only associated to age over 60years (odds ratio [OR] = 5.5; 95% confidence interval [CI],1.4-21.9; p=0.019) and to tumor size of 1cm or greater (OR=3.6, 95% CI, 1.2-10.3; p=0.016). The BRAF(T1799A) mutation was not associated to histological subtype, metastasis, recurrence, more aggressive treatments (ablative I(131) therapy or surgery), or PTC persistence at the end of follow-up. CONCLUSIONS: The BRAFT1799A mutation is associated to age over 60 and a tumor size of 1cm or greater, but not to other clinicopathological characteristics, tumor recurrence or PTC persistence.

Efectividad diagnóstica de la tomografía por emisión de positrones con18fluorodeoxiglucosa asociada a tomografía axial en la discriminación de benignidad o malignidad de las lesiones suprarrenales / Diagnostic efficacy and discriminatory capacity of positron emission tomography combined with axial tomography of adrenal lesions

Introducción: Se analiza la utilidad de la tomografía por emisión de positrones asociada a la tomografía axial computarizada (PET-TAC) en el diagnóstico de benignidad o malignidad de lesiones suprarrenales. Material y métodos: Estudio retrospectivo, entre junio de 2005 y mayo de 2009, de una serie consecutiva de pacientes a los que se les realizó una PET-TAC para el estudio de patología suprarrenal con sospecha de malignidad. Se valoraron la presencia de captaciones focales, su valor estándar de máxima captación (SUV), y la ratio del valor máximo suprarrenal/hepático. Se analizó la sensibilidad, especificidad, valor predictivo positivo y negativo de la prueba, y los valores de captación máxima adrenal y la ratio para los que la rentabilidad diagnóstica fue máxima. Resultados: Se incluyeron 15 pacientes. El diagnóstico final reveló malignidad en ocho y benignidad en siete. Diez pacientes presentaron captación suprarrenal: tres en lesiones benignas y siete en neoplasias, con un valor de captación medio de 6,3 (3,2 en benignas y 9 en malignas). La ratio media suprarrenal/hepático fue de 1,8 (0,9 en lesiones benignas y 2,6 en malignas). Cuando se relaciona la presencia de captación suprarrenal con el diagnóstico final de malignidad, obtuvimos una sensibilidad del 87,5%, especificidad del 57,1%, valor predictivo positivo del 70% y negativo del 80%. Un valor de corte de SUV de 6, o una ratio de captación suprarrenal/hepática de 2, proporciona una sensibilidad de 75%, especificidad de 100%, valor predictivo positivo de 100% y negativo de 77,7%. Conclusiones: La PET-TAC posee una alta capacidad para discriminar entre benignidad o malignidad en la patología adrenal estudiada (AU)

Introduction: The usefulness of 18fluorodeoxyglucose positron emission tomography combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are benign or malignant is assessed. Material and methods: A retrospective study conducted between June 2005 and May 2009 on a consecutive series of patients on whom a PET-CT scan was performed to study suspected malignant adrenal disease. Focal uptakes were assessed, along with the maximum standard uptake value (SUV), and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity, positive and negative predictive value of the test, the maximum adrenal uptake values and the ratio for those where the diagnostic yield was maximum. Results: Fifteen patients were included. The final diagnosis showed malignancy in eight and seven were benign. Ten patients had adrenal uptake: three in benign lesions and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in benign and 2.6 in malignant lesions). When the presence of adrenal uptake is associated with a final diagnosis of malignancy, we obtained a sensitivity of 87.5%, a specificity of 57.1%, and a positive and negative predictive value of 70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a positive and negative predictive value of 100% and 77.7%, respectively. Conclusions: PET-CT has a high ability to discriminate between benign and malignant lesions in the adrenal disease studied (AU)

[Diagnostic efficacy and discriminatory capacity of positron emission tomography combined with axial tomography of adrenal lesions]. / Efectividad diagnóstica de la tomografía por emisión de positrones con (18)fluorodeoxiglucosa asociada a tomografía axial en la discriminación de benignidad o malignidad de las lesiones suprarrenales.

INTRODUCTION: The usefulness of 18fluorodeoxyglucose positron emission tomography combined with axial tomography (PET-CT) in diagnosing whether adrenal tumours are benign or malignant is assessed. MATERIAL AND METHODS: A retrospective study conducted between June 2005 and May 2009 on a consecutive series of patients on whom a PET-CT scan was performed to study suspected malignant adrenal disease. Focal uptakes were assessed, along with the maximum standard uptake value (SUV), and the ratio of the maximum adrenal/hepatic value. The sensitivity, specificity, positive and negative predictive value of the test, the maximum adrenal uptake values and the ratio for those where the diagnostic yield was maximum. RESULTS: Fifteen patients were included. The final diagnosis showed malignancy in eight and seven were benign. Ten patients had adrenal uptake: three in benign lesions and seven in neoplasias, with a mean uptake value of 6.3 (3.2 in benign lesions and 9.0 in malignant lesions). The mean adrenal/hepatic ratio was 1.8 (0.9 in benign and 2.6 in malignant lesions). When the presence of adrenal uptake is associated with a final diagnosis of malignancy, we obtained a sensitivity of 87.5%, a specificity of 57.1%, and a positive and negative predictive value of 70% and 80%, respectively. An SUV cut-off value of 6, or an adrenal/hepatic uptake ratio of 2, gave a sensitivity of 75%, a specificity of 100%, and a positive and negative predictive value of 100% and 77.7%, respectively. CONCLUSIONS: PET-CT has a high ability to discriminate between benign and malignant lesions in the adrenal disease studied.