Ensemble Deep Learning Model for Multicenter Classification of Thyroid Nodules on Ultrasound Images.

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

The impact of surgery on quality of life, esophageal motility, and tracheal anatomy and airflow in patients with benign nodular goiter.

Surgery - is it any good for goiter? In patients with goiter the benefits of thyroid surgery have previously rarely been investigated, as only few alternatives existed. However, the increasing evidence of the advantages with non-surgical substitutes with lower costs and preferable risk profiles prompted us to investi-gate the evidence base for thyroid surgery thoroughly. This thesis consists of three published studies investigating the impact of thyroidectomy on: 1) changes in disease-specific quality of life, 2) swallowing symptoms and esophageal motility, and 3) tracheal anatomy and airflow, in a cohort of patients with benign nodular goiter.

Temporal Changes in Thyroid Nodule Volume: Lack of Effect on Paranodular Thyroid Tissue Volume.

BACKGROUND: The term "nodular goiter" has long been used to refer to a nodular thyroid gland, based on the assumption that nodule growth may be associated with hyperplasia of the surrounding non-nodular tissue. The aim of this prospective, multicenter, observational study was to determine whether nodule growth is accompanied by growth in the non-nodular tissue. METHODS: Eight Italian thyroid-disease referral centers enrolled 992 consecutive patients with one to four benign nodules. Nodular and non-nodular thyroid tissue volumes were assessed for five years with annual ultrasound examinations. RESULTS: In participants whose nodules remained stable (n = 839), thyroid volumes did not change (baseline 15.0 mL [confidence interval (CI) 14.5-15.6]; five-year evaluation 15.1 mL [CI 14.5-15.7]). In participants with significant growth of one or more nodule (n = 153), thyroid volumes increased and by year 5 were significantly greater than those of the former group (17.4 mL [CI 16-18.7]). In 76 individuals with unilateral nodules that grew, the mean nodular lobe volume significantly exceeded that of the contralateral lobe (8.6 mL [CI 7.4-9.8] vs. 6.7 mL [CI 6-7.4]). The unaffected lobe volumes remained stable over time, while nodular lobes grew steadily and were significantly greater at the end of follow-up (10.1 mL [CI 8.9-11.3]). Excluding the volume of the largest growing nodule in these cases, the remaining volume of the affected lobe remained virtually unchanged with respect to its baseline value. Furthermore, there was no significant difference in the non-nodular tissue volume between the unaffected lobe and the affected lobe (with the largest growing nodule volume subtracted), both at baseline and at the end of follow-up. CONCLUSIONS: The growth of thyroid nodules is a local process, not associated with growth of the surrounding non-nodular tissue. Therefore, a normal-sized thyroid containing nodules should be referred to as a "uni- or multinodular thyroid gland" and considered a distinct entity from "uni- or multinodular goiter."

Fine needle aspiration cytology of 650 thyroid nodules operated for multinodular goiter: a cyto-histological correlation based on the new Italian cytological classification (siapec 2014).

The new Italian cytological classification (SIAPEC 2014) of thyroid nodules, in line with those of Bethesda and BTA-RCPath, replaces the previous TIR3 class with two new classes (TIR3A and TIR3B), which correspond to different risks of malignancy and clinical actions required. The present study was conducted to evaluate the diagnostic accuracy of the new SIAPEC classification as opposed to its previous version (SIAPEC 2007). Preoperative cytology was compared with the final histology obtained from 650 consecutive patients who underwent total thyroidectomy for multinodular goiter. Of this total, 434 patients (group A) had their cytological diagnosis based on the old SIAPEC 2007 classification and 216 patients (group B) had their cytological diagnosis based on the SIAPEC 2014 classification. In group A 111 patients (25.6%) had a TIR3 diagnosis, while in group B 52 patients (24.1%) received a TIR3 diagnosis, of whom 30 had TIR3A and 22 had TIR3B. In group A, 46 (41.4%) out of the 111 patients with TIR3 diagnosis had, based on histology, a thyroid carcinoma. In group B, only 2 (6.7%) out of 30 patients with TIR3A diagnosis had a thyroid carcinoma. This rate of malignancy was significantly lower (p less than 0.001) than that observed in patients with TIR3B diagnosis, in which 12 (54.5%) out of 22 patients had a carcinoma. The observations here reported show that, in respect to the previous version, the new Italian cytological classification provides greater diagnostic accuracy for detecting thyroid nodule malignancy.

The diagnostic accuracy of fine-needle cytology of Hurthle cell lesions; A comprehensive cytological, clinical and ultrasonographic experience.

BACKGROUND: Fine-needle cytology (FNC) diagnosis and pre-operative classification of Hurthle cells (HC) lesions may be difficult. Rapid on-site evaluation (ROSE) enhances the efficiency of FNC, mainly when utilized in close combination to clinical and ultrasound (US) data. OBJECTIVE: to describe an experience on HC FNC with contextual clinical,US and ROSE evaluation and assess if this comprehensive approach improves the FNC accuracy of HC lesions. METHODS: FNC of 112 HC lesion were diagnosed and classified, according to the Bethesda system, by clinical, US and ROSE in one year. All the cases were controlled by follow-up and histology when performed. RESULTS: Eighty-five cases were diagnosed HC rich goiter or Hashimoto thyroiditis and were classified THY2; 5 cases were diagnosed hyperplastic nodular goiter and classified THY3A. Eight cases were diagnosed suspect neoplasia and classified THY3B. Two cases were diagnosed suspect HC papillary thyroid carcinoma (PTC) and classified THY4 and 2 cases were diagnosed HC-PTC and classified THY5. THY3B, THY4, THY5 and 1 THY3A were histologically controlled. FNC were confirmed in 14 out of the 17 THY3-THY5 cases. CONCLUSIONS: A comprehensive diagnostic approach that include FNC, clinical data, US and ROSE improves the diagnosis and classification of HC lesions.

Evaluation of cytopathological findings in thyroid nodules with macrocalcification: macrocalcification is not innocent as it seems / Avaliação dos achados citopatológicos em nódulos tiroidianos com macrocalcificações: elas não são tão inocentes como parecem

Objective Microcalcification is strongly correlated with papillary thyroid cancer. It is not clear whether macrocalcification is associated with malignancy. In this study, we aimed to assess the result of fine needle aspiration biopsies (FNAB) of thyroid nodules with macrocalcifications. Subjects and methods We retrospectively evaluated 269 patients (907 nodules). Macrocalcifications were classified as eggshell and parenchymal macrocalcification. FNAB results were divided into four groups: benign, malignant, suspicious for malignancy, and non-diagnostic. Results There were 79.9% female and 20.1% male and mean age was 56.9 years. Macrocalcification was detected in 46.3% nodules and 53.7% nodules had no macrocalcification. Parenchymal and eggshell macrocalcification were observed in 40.5% and 5.8% nodules, respectively. Cytologically, malignant and suspicious for malignancy rates were higher in nodules with macrocalcification compared to nodules without macrocalcification (p = 0.004 and p = 0.003, respectively). Benign and non-diagnostic cytology results were similar in two groups (p > 0.05). Nodules with eggshell calcification had higher rate of suspicious for malignancy and nodules with parenchymal macrocalcification had higher rates of malignant and suspicious for malignancy compared to those without macrocalcification (p = 0.01, p = 0.003 and p = 0.007, respectively). Conclusions Our findings suggest that macrocalcifications are not always benign and are not associated with increased nondiagnostic FNAB results. Macrocalcification, particularly the parenchymal type should be taken into consideration. Arq Bras ...

Objetivo A microcalcificação está fortemente correlacionada com o câncer papilar de tiroide. Não está claro se a macrocalcificação também está associada com malignidade. Neste estudo, nosso objetivo foi avaliar o resultado da biópsia de aspiração por agulha fina (FNAB) de nódulos tiroidianos com macrocalcificações. Sujeitos e métodos Avaliamos retrospectivamente 269 pacientes (907 nódulos). As macrocalcificações foram classificadas como periféricas (casca de ovo) ou parenquimatosas (interna). Os resultados da FNAB foram divididos em quatro grupos citológicos: benignos, com malignidade, suspeita de malignidade e não diagnósticos. Resultados Das amostras, 79,9% foram coletadas de mulheres e 20,1% de homens, e a idade média foi de 56,9 anos. A macrocalcificação foi detectada em 46,3% dos nódulos, e em 53,7% dos nódulos não havia macrocalcificação. A macrocalcificação parenquimatosa e periférica foi observada em 40,5% e 5,8% dos nódulos, respectivamente. Em termos citológicos, a malignidade e suspeita de malignidade foram mais comuns em nódulos com macrocalcificação em comparação com nódulos sem macrocalcificação (p = 0,004 e p = 0,003, respectivamente). Resultados benignos e não diagnósticos da citologia foram similares em ambos os grupos (p > 0,05). Os nódulos com calcificações periféricas apresentaram uma taxa maior de suspeita de malignidade e os nódulos com macrocalcificação parenquimatosa apresentaram ...

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Evaluation of cytopathological findings in thyroid nodules with macrocalcification: macrocalcification is not innocent as it seems.

OBJECTIVE: Microcalcification is strongly correlated with papillary thyroid cancer. It is not clear whether macrocalcification is associated with malignancy. In this study, we aimed to assess the result of fine needle aspiration biopsies (FNAB) of thyroid nodules with macrocalcifications. SUBJECTS AND METHODS: We retrospectively evaluated 269 patients (907 nodules). Macrocalcifications were classified as eggshell and parenchymal macrocalcification. FNAB results were divided into four groups: benign, malignant, suspicious for malignancy, and non-diagnostic. RESULTS: There were 79.9% female and 20.1% male and mean age was 56.9 years. Macrocalcification was detected in 46.3% nodules and 53.7% nodules had no macrocalcification. Parenchymal and eggshell macrocalcification were observed in 40.5% and 5.8% nodules, respectively. Cytologically, malignant and suspicious for malignancy rates were higher in nodules with macrocalcification compared to nodules without macrocalcification (p = 0.004 and p = 0.003, respectively). Benign and non-diagnostic cytology results were similar in two groups (p > 0.05). Nodules with eggshell calcification had higher rate of suspicious for malignancy and nodules with parenchymal macrocalcification had higher rates of malignant and suspicious for malignancy compared to those without macrocalcification (p = 0.01, p = 0.003 and p = 0.007, respectively). CONCLUSIONS: Our findings suggest that macrocalcifications are not always benign and are not associated with increased nondiagnostic FNAB results. Macrocalcification, particularly the parenchymal type should be taken into consideration.

[Surgical therapy for thyroid gland malignancies]. / Chirurgie der Schilddrüsenmalignome.

Surgical therapy for thyroid neoplasms is based on tumor histology and comprises stage-adapted procedures with a high degree of inter-individual variability. This can range from waiting and monitoring, to extensive multivisceral surgery. Grouping together histologically different types of malignancies leads to false assumptions when gauging the radicality of surgery necessary in each particular case. Surgical therapy requires not only an understanding of the biological behavior of the tumor and the risk that it or the therapy poses to the patient, but also knowledge of a wide surgical spectrum of limited and complex resection procedures in the neck and thorax region. The following recommendations are based primarily on the guidelines of the Surgical Working Group for Endocrinology of the German Society for General and Visceral Surgery as well as on the authors' own experience and, where indicated, the guidelines of other working groups.

Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study.

OBJECTIVE: Few population-based studies have described the epidemiology of subtypes of hyperthyroidism. DESIGN: A prospective population-based study, monitoring two well-defined Danish cohorts in Aalborg with moderate iodine deficiency (n=311 102) and Copenhagen with only mild iodine deficiency (n=227 632). METHODS: A laboratory monitoring system identified subjects with thyroid function tests suggesting overt hyperthyroidism (low s-TSH combined with high s-thyroxine or s-triiodothyronine). For all subjects, we collected information on medical history, thyroid scintigraphy and thyroid hormone receptor antibody (TRAb) measurement. Information was used to disprove or verify primary overt hyperthyroidism and to subclassify hyperthyroidism into nosological disorders. RESULTS: From 1997 to 2000 (2 027 208 person-years of observation), we verified 1682 new cases of overt hyperthyroidism. The overall standardized incidence rate (SIR) per 100 000 person-years was 81.6, and was higher in Aalborg compared with Copenhagen (96.7 vs 60.0, P<0.001), giving an SIR ratio (SIRR (95% confidence interval (CI))) between moderate versus mild iodine-deficient areas of 1.6 (1.4-1.8). Nosological types of hyperthyroidism (percentage/SIRR (95% CI)): multinodular toxic goitre (MNTG) 44.1%/1.9 (1.6-2.2), Graves' disease (GD) 37.6%/1.2 (0.99-1.4), solitary toxic adenoma (STA) 5.7%/2.4 (1.3-3.5), 'mixed type' hyperthyroidism (TRAb-positive, scintigraphicly multinodular) 5.4%/6.0 (3.0-12), subacute thyroiditis 2.3%/0.9 (0.4-1.4), postpartum thyroid dysfunction 2.2%/1.6 (0.8-3.0), amiodarone-associated hyperthyroidism 0.8%/7.1 (1.1-65), hyperthyroidism after thyroid radiation 0.7%/12.3 (0.8-50), lithium-associated hyperthyroidism 0.7%/0.97 (0.4-4.8) and hyperthyroidism caused by various other factors 0.7%. Lifetime risk for overt hyperthyroidism was 10.5%/6.5%/2.4% (females/all/males). CONCLUSION: Hyperthyroidism was common in Denmark with MNTG and GD as dominating entities. The higher incidence of hyperthyroidism in the most iodine-deficient region was caused by higher frequency of MNTG, 'mixed-type', STA and amiodarone-associated hyperthyroidism.

ACTUALIZACIÓN EN MEDICINA DE FAMILIA: Manejo de la patología tiroidea en Atención Primaria III. Bocio simple. Enfermedad nodular del tiroides: bocio multinodular y nódulo tiroideo / UPDATE IN FAMILY MEDICINE: Management of thyroid disease in Primary Care III. Simple goiter. Nodular thyroid disease: multinodular goiter and thyroid nodule

La patología tiroidea constituye un trastorno muy común en la consulta de Atención Primaria. Para completar esta revisión de la patología tiroidea y el manejo de los problemas de tiroides en Atención Primaria, en este último artículo se van a tratar problemas muy importantes, ya sea por su frecuencia, como el bocio simple y el bocio multinodular, o por su gravedad potencial, como en el caso del nódulo tiroideo y el cáncer de tiroides. La importancia clínica de la enfermedad nodular del tiroides reside en su posible malignización, la disfunción hormonal y la compresión local de estructuras anatómicas vecinas. Por tanto, el manejo del paciente con enfermedad nodular del tiroides va a depender de la función tiroidea, el tamaño del bocio y la presencia o no de un nódulo dominante

Thyroid disease is a very common disorder in Primary Carevisits. To complete this review of thyroid disease and themanagement of thyroid problems in Primary Care, this lastarticle will deal with very important problems, either due totheir frequency, such as simple goiter and multinodular goiter,or to their potential severity, such as the case of thyroidnodule and thyroid cancer. The clinical importance of nodularthyroid disease is found in its potential malignancy, hormonedysfunction and local compression of the neighboringanatomical structures. Thus, the management of the patientwith nodular thyroid disease will depend on the thyroidfunction, size of the goiter and presence or not of a dominantnodule (AU)

[Cytological classification of nontoxic nodular goiter].

By comparing the cytological and histological data on thyroid nodular lesions in 715 patients, the authors have arrived at the conclusion that with a cytological response of colloidal goiter and colloidal goiter with adenomatosis, the cancer detection rate is not greater than 4%. With a cytological response of adenomatosis with atypia and follicular tumor, a malignancy occurs in 9 to 13%. It is recommended that cytological data should be grouped by the type of a morphological classification of thyroid nodular diseases: colloidal goiter (with regression, proliferation, adenomatosis, cystic cavity); tumors (adenomatosis with atypia, follicular tumor); cancer.

[Histopathological diagnosis of thyroid cancer in a multicenter trial]. / Badanie wieloosrodkowe rozpoznan raka tarczycy.

INTRODUCTION: In the front of the problems related to the differentiation between benign and malignant thyroid tumors we decided to perform a multicentre study in order to validate diagnoses of malignant thyroid tumors and assess the inter-observer variability. MATERIAL AND METHODS: Material included 690 cases of malignant and benign thyroid lesions with primary histopathology established in 1985-1999. These cases were selected to multicentre study. The studies were sent from centres which agreed to participate in the project and than coded in the independent centre--Department of Nuclear Medicine and Endocrine Oncology. 40 pathologists from 25 centres provided their diagnoses which were compared with the reference ones. RESULTS: 10 547 diagnoses were evaluated, both on their accuracy of the distinction between malignant and benign lesions and on their accuracy of cancer histotype definition. The reference diagnosis was made by an agreement between four expert pathologists (D.L., S.S., J.S. and A.K.). The participants diagnosed 21% of cases differently than experts. Concerning the diagnosis of cancer histotype, the difference between participants diagnosis and the reference one was even higher. The best concordance was achieved in the diagnosis of papillary thyroid cancer, however, on the cost of cancer overdiagnosis by some participants. Follicular cancer was diagnosed accurately only in 75.4% of cases. CONCLUSION: The study documents a high inter-observer variability of thyroid cancer diagnosis and confirms the lesser accuracy of diagnosis of follicular cancer.

Global DNA methylation evaluation: potential complementary marker in differential diagnosis of thyroid neoplasia.

The implications of global DNA hypomethylation were recently reported in several models of tumorigenesis. Little is known about this epigenetic event in thyroid neoplasia. The study aimed to evaluate the status of global DNA methylation in several types of thyroid tumors using a monoclonal antibody specific for 5-methylcytidine (5-mc) and to define the diagnosis potential of this marker. 5-mc immunostaining scores were calculated in 17 papillary thyroid carcinomas (PTC), 6 follicular thyroid carcinomas (FTC), 16 follicular adenomas (FA), 19 nodular goiters (NG) and ten Hürthle cells adenomas (HCA). The expression of galectin-3 was also evaluated. Computerized image analysis showed a significant lower level of 5-mc immunostaining in thyroid carcinoma when compared with benign tumors or adjacent normal thyroid parenchyma (P<0.0001). Overall, 5-mc accuracy to distinguish malign from benign thyroid tumors was similar to that of galectin-3 (89% versus 87%, P>0.05). The combination of 5-mc with galectin-3 led to an excellent accuracy level of 96%. Among follicular neoplasia 5-mc accuracy to differentiate malign tumors trends to be higher than galectin-3 one (90% versus 66%, P=0.06). These data stress the necessity of epigenetic events evaluation among thyroid nodules and propose global DNA methylation assessment as a potential diagnostic tool to combine with other valuable markers.

[Multinodular goiter as an organ disease: study of continual nodulogenesis. Biological bases indicating total thyroidectomy]. / Il gozzo multinodulare come malattia d'organo: studio della nodulogenesi incessante. Basi biologiche per l'indicazione alla tiroidectomia totale.

Multinodular goitre is a very common pathology among people especially female adult and represents more than 90% of the thyroid surgery. We analyzed 37 patients, demonstrating that the whole gland is progressively affected by an incessant nodulogenesis and we confirm the necessity of total thyroidectomy in order to eliminate any persistent pathology.

[Clinical and morphological characteristics of thyroid adenomatosis]. / Kliniko-morfologicheskaia kharakteristika adenomatoza shchitovidnoi zhelezy.

Surgical (374 cases) and puncture (6148 cases) material from patients with multinodular goiter was studied. Definitions and a working classification characterizing morphological and cytological signs of adenomatous goiter were formulated. Prognostic significance of thyroid adenomatosis and approaches to its treatment in multinodular goiter are shown.

[Dystopic goiter--aspects of definition and surgical therapy]. / Dystope Struma--Aspekte der Definition und chirurgischen Therapie.

The incidence in the literature of dystopic goiter depends on classification of the false endothoracic goiter ("substernal goiter") as dystopic and varies from 2 to 20%. From November 1989 through April 1993 we operated on 530 patients with benign nodular goiters. In 84 patients (15.8%) the operation proved a dystopic goiter. We showed that difficulties in comparing our data with published series were due to misnomers of the dystopic goiter. The dystopic goiter comprises the true endothoracic goiters (alliata vera and isolata vera) as well as the false endothoracic goiters (substernal goiter). The precise classification of the dystopic goiter is crucial to an optimal operative strategy reducing postoperative morbidity.

Nodular thyroid disease and cancer.

Different possibilities of solitary or multinodular involvement of the thyroid gland are described. Because of the broad spectrum of malignancy there exists a controversy and widespread divergence of opinion regarding the incidence, malignancy, classification and treatment of thyroid cancer.