Browsing by Author "Tala, Hernán"
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Item A 10-gene classifier for indeterminate thyroid nodules: development and multicenter accuracy study(American Thyroid Association, 2017) González, Hernán; Martínez, José R.; Vargas, Sergio; Solar, Antonieta; Veliz, Loreto; Cruz, Francisco; Arias, Tatiana; Loyola, Soledad; Horvath, Eleonora; Tala, Hernán; Traipe, Eufrosina; Meneses, Manuel; Marín, Luis; Wohllk, Nelson; Diaz, René; Véliz, Jesús; Pineda, Pedro; Arroyo, Patricia; Mena, Natalia; Bracamonte, Milagros; Miranda, Giovanna; Bruce, Elsa; Urra, SoledadBACKGROUND: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology. METHODS: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies. RESULTS: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64-82% and a negative predictive value of 97-99% in patients with a cancer prevalence range of 20-40%. CONCLUSIONS: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.Item Biochemical persistence in thyroid cancer: is there anything to worry about?(Springer, 2014) Pitoia, Fabián; Abelleira, Erika; Tala, Hernán; Bueno, Fernanda; Urciuoli, Carolina; Cross, GracielaTo evaluate the outcome of differentiated thyroid cancer (DTC) patients with biochemical persistence of disease (BP) after initial treatment (total thyroidectomy with or without lymph node dissection (LND) and thyroid remnant ablation). BP was defined as suppressed thyroglobulin (Tg) levels <1 ng/ml and rhTSH-stimulated thyroglobulin (St-Tg) >1ng/ml, with no evidence of structural disease. Structural persistence/recurrence (SPR): clinically identifiable disease. We reviewed 278 records of DTC patients. Tg-Ab positive patients (n = 73) were excluded and 32 were included in the analysis (median age 45 years, range 18–77 years); risk of recurrence ATA was: low in 38 %, Intermediate in 47 %, and high in 15 % of patients. All subjects had Tg levels <1 ng/ml under thyroid hormone therapy. Patients were divided into three groups: Group 1: St-Tg 1–2 ng/ml, n = 6; Group 2: St-Tg 2–10 ng/ml, n = 17; Group 3: St-Tg > 10 ng/ml, n = 9. In 5/32 (16 %) patients, SPR was observed after a median follow-up of 6 years (range 2–23 years). In Group 1: all patients were considered with no evidence of disease after a median follow-up of 2 years (range 1–2.5 years). In Group 2: 13/17 (76.5 %) patients continued with only a BP after a median follow-up of 4 years (range 2–10 years) and 4/17 (23.5 %) patients with intermediate risk of recurrence had a structural persistence (lymph nodes metastasis) diagnosed between 1 and 3.5 years after initial assessment. Following LND, all of them remained with BP after a median of 2 years (range 1.5–5 years). In Group 3: 8/9 (89 %) patients had BP after a median follow-up of 7 years (range 2–23 years) and 1/9 (11 %) had a SPR diagnosed 28 months after initial assessment, LND was indicated but he continued with BP, 5 years after the second surgery. Most patients with DTC and BP present an indolent course of the disease. In these patients the diagnosis of the structural recurrence did not change the outcome because all of them continued with BP.Item Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED(Sociedad Medica de Santiago, 2017) Tala, Hernán; Díaz, René; Domínguez, José; Sapunar, Jorge; Pineda, Pedro; Arroyo, Patricia; Barberán, Marcela; Cabané, Patricio; Cruz, Francisco; Gac, Patricio; Glasinovic, Andrea; González, Hernán; Grob, Francisca; Hidalgo, Maria; Jaimovich, Rodrigo; Lanas, Alejandra; Liberman, Claudio; Lobo, Maite; Madrid, Arturo; Moreno, Marcela; Mosso, Lorena; Munizaga, Fernando; Ortiz, Eugenia; Osorio, Fernando; Slater, Jeannie; Solar, Antonieta; Stehr, Carlos; Vásquez, Félix; Véliz, Jesús; Villaseca, Roberto; Wohllk, NelsonThe thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.Item Prospective validation of the ultrasound based TIRADS (Thyroid Imaging Reporting And Data System) classification: results in surgically resected thyroid nodules(Springer, 2017) Horvath, Eleonora; Silva, Claudio; Majlis, Sergio; Rodriguez, Ignacio; Skoknic, Velimir; Castro, Alex; Rojas, Hugo; Niedmann, Juan Pablo; Madrid, Arturo; Capdeville, Felipe; Whittle, Carolina; Rossi, Ricardo; Dominguez, Miguel; Tala, HernánOBJECTIVE: To assess performance of TIRADS classification on a prospective surgical cohort, demonstrating its clinical usefulness. METHODS: Between June 2009 and October 2012, patients assessed with pre-operative ultrasound (US) were included in this IRB-approved study. Nodules were categorised according to our previously described TIRADS classification. Final pathological diagnosis was obtained from the thyroidectomy specimen. Sensitivity, specificity, positive/negative predictive values and likelihood ratios were calculated. RESULTS: The study included 210 patients with 502 nodules (average: 2.39 (±1.64) nodules/patient). Median size was 7 mm (3-60 mm). Malignancy was 0 % (0/116) in TIRADS 2, 1.79 % (1/56) in TIRADS 3, 76.13 % (185/243) in TIRADS 4 [subgroups: TIRADS 4A 5.88 % (1/17), TIRADS 4B 62.82 % (49/78), TIRADS 4C 91.22 % (135/148)], and 98.85 % (86/87) in TIRADS 5. With a cut-off point at TIRADS 4-5 to perform FNAB, we obtained: sensitivity 99.6 % (95 % CI: 98.9-100.0), specificity 74.35 % (95 % CI: 68.7-80.0), PPV 82.1 % (95 % CI: 78.0-86.3), NPV 99.4 % (95 % CI: 98.3-100.0), PLR 3.9 (95 % CI: 3.6-4.2) and an NLR 0.005 (95 % CI: 0.003-0.04) for malignancy. CONCLUSION: US-based TIRADS classification allows selection of nodules requiring FNAB and recognition of those with a low malignancy risk. KEY POINTS: • TIRADS classification allows accurate selection of thyroid nodules requiring biopsy (TIRADS 4-5). • The recognition of benign/possibly benign patterns can avoid unnecessary procedures. • This classification and its sonographic patterns are validated using surgical specimens.Item Radioiodine-Induced Salivary Gland Damage Detected by Ultrasonography in Patients Treated for Papillary Thyroid Cancer: RAI activity and risk(2020) Horvath, Eleonora; Skoknic, Velimir; Majlis, Sergio; Tala, Hernán; Silva, Claudio; Castillo, Eliette; Whittle, Carolina; Niedmann, Juan Pablo; González, PaulinaAn important side effect of radioactive iodine (RAI) therapy in patients treated for papillary thyroid cancer (PTC) is chronic sialadenitis. Neck ultrasonography (US) easily recognizes radioiodine-induced salivary gland abnormalities. The objectives of this study were to determine the prevalence of US-detected sialadenitis caused by RAI and to identify the risk factors associated with this damage. Methods: This nonconcurrent cohort study includes all PTC-operated patients who were treated with RAI between 2007 and 2017 and were systematically evaluated with preoperative and follow-up neck US that included targeted exploration of the major salivary glands. Patients with pre-existing salivary gland diseases were excluded. The anatomical damage (diminished glandular volume, wavy contours, hypoechogenicity, and heterogeneity) was qualitatively assessed and compared with the preoperative study. RAI activity, sex, age, and preparation method were evaluated as risk factors using univariate and multivariate analyses with logistic regression. Results: Enrolled in this study were 570 patients who received a median RAI activity of 3700 MBq (100 mCi). On US, we found 143 patients (25.1%) with damage in at least one of their salivary glands: all had parotid damage (77 bilaterally) and 14 (9.8%) also had submandibular gland damage (7 of them bilaterally). The multivariate analysis indicated that the risk of sialadenitis was significantly (p < 0.01) correlated with both RAI activity and sex (14.1% of males vs. 28.5% of females). However, the main risk factor was RAI activity; no injury was detected in 156 patients who received 1110 MBq (30 mCi) and 1850 MBq (50 mCi) of RAI. In the groups of patients receiving 3700 MBq (100 mCi), 5550 MBq (150 mCi) and ≥7400 MBq (≥200 mCi), atrophy was found in 21%, 46.9%, and 77.7% of patients, respectively. Age and preparation method were not related to an increased risk of atrophy in this study. Conclusions: Chronic sialadenitis is common and affects approximately one fourth of patients who receive 3700 MBq (100 mCi) or higher RAI activity. The main risk factor for this injury is the total RAI activity administered. By using the lowest effective activity possible, irreversible anatomical damage in salivary glands can be minimized. US is an excellent tool to diagnose post-RAI atrophy.