Pregnancy has no significant impact on the prognosis of differentiated thyroid cancer

ABSTRACT Objective: To evaluate the impact of pregnancy on differentiated thyroid carcinomas (DTC) behavior Subjects and methods: Retrospective study of patients diagnosed with DTC before or during pregnancy and treated with standard therapy. In women diagnosed with DTC before pregnancy, we evaluated the occurrence of progression according to categories of response to therapy based on imaging and non-stimulated thyroglobulin (TG) levels. Results: Of 96 analyzed patients, 76 became pregnant after DTC treatment and 20 were diagnosed with DTC during pregnancy. Among women who became pregnant after a DTC diagnosis, no difference was observed regarding response to therapy before and after pregnancy. Disease progression after pregnancy was documented in six of these patients, while seven of them presented progression before pregnancy but were only treated after delivery. Patients with DTC diagnosed during pregnancy had a higher rate of distant metastases at diagnosis (30%) compared with the patients who became pregnant after DTC diagnosis (9.2%, p = 0.01). Conclusion: Pregnancy had no impact on the natural course of DTC. Disease progression after pregnancy was limited and probably related to more aggressive disease and higher risk stratification at diagnosis. Still, mild disease progression may have occurred asymptomatically in some patients.

Prognostic factors in patients with advanced differentiated thyroid cancer treated with multikinase inhibitors - a single Brazilian center experience

ABSTRACT Objective: The aim of this study was to describe the real-world experience multikinase inhibitors (MKI) in the treatment advanced differentiated thyroid carcinoma (DTC) refractory to radioactive iodine (RAIR) therapy. Subjects and methods: We reviewed the records of all patients with MKI-treated DTC from 2010 to 2018. Progression free survival (PFS), response rates (RR) and adverse events (AE) profiles were assessed. Clinical parameters were compared between groups with different outcomes (disease progression and death) to identify possible prognostic factors and benefit from treatment. Results: Forty-four patients received MKI for progressive RAIR DTC. Median PFS was 24 months (10.2-37.7) and median overall survival (OS) was 31 months. Best overall response was complete response in one patient (4.5%), partial response in nine (20.4%), stable disease in twenty-two (50%), and progressive disease (PD) in twelve (27.3%). Seventy-two point 7 percent patients had clinical benefit and AE were mild in most cases (82.7%). Progressive patients were more likely to have FDG positive target lesion than those who did not progress (p = 0.033) and higher maximum SUV on target lesions (p = 0.042). Presence of lung-only metastasis and lower thyroglobulin (Tg) during treatment was associated with stable disease (p = 0.015 and 0,049, respectively). Patients with shorter survival had larger primary tumor size (p = 0.015) and higher maximum SUV on target lesions (p = 0.023). Conclusion: Our findings demonstrate safety and effectiveness of MKI in patients with advanced RAIR DTC. We were able to identify as possible prognostic markers of better outcomes: absence of FDG uptake on target lesions, lower maximum SUV on PET-CT, presence of lung-only metastasis and lower Tg during treatment.

Cholestatic syndrome as initial manifestation of pancreatic metastasis of papillary thyroid carcinoma: case report and review

SUMMARY Most papillary thyroid carcinomas (PTC) harbor excellent prognosis. Although rare, distant metastases normally occur in lungs and/or bones. Here we describe a rare case of pancreatic metastasis presenting with rapid onset cholestatic syndrome. A literature review was also performed. A 73-year-old man with a high risk PTC was submitted to total thyroidectomy (TT) followed by radioiodine therapy. After initial therapy, he persisted with progressive rising serum thyroglobulin levels but with no evidence of structural disease. Recently, the patient presented with a rapid onset and progressive cholestatic syndrome. A 4 cm lesion in pancreas was identified, with echoendoscopy fine-needle aspiration biopsy (FNAB) confirming a pancreatic metastasis from PTC. The patient was submitted to a successful pancreaticoduodenectomy. Pancreatic metastases of PTC are rare and few long-term follow-up data are available to guide management. Fourteen cases were former reported, mean age was 65.7 years-old with mean time between PTC and pancreatic metastasis diagnosis of 7.9 years. Nine of them had another distant metastasis, nine were diagnosed by FNAB and just two received sorafenib.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy

ABSTRACT Objective To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). Subjects and methods A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. Results From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). Conclusions Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

Metastatic lymph node characteristics as predictors of recurrence/persistence in the neck and distant metastases in differentiated thyroid cancer

ABSTRACT Objective: The aim of this study was to evaluate the association between this characteristic and outcomes in patients with lymph node metastasis in a Brazilian cohort. Subjects and methods: This study examined a retrospective cohort of adult patients diagnosed with differentiated thyroid cancer and lymph node metastases from 1998 to 2015 in two referral centers. Number, location, size and extranodal extension (ENE) of metastatic lymph nodes were assessed and correlated with response to initial therapy. Results: A greater number of metastatic nodes, larger size, presence of lateral neck disease and ENE were all associated with a lower probability of achieving an excellent response to initial therapy (p ≤ 0.05 for all these parameters). Local recurrent disease had a significant association with lymph node number (6 in the recurrence/persistence group versus 4 in the non-recurrent group; p = 0.02) and ENE (19.2 versus 75%, p = 0.03). Lateral neck disease was the only characteristic associated with distant metastasis and was present in 52.1% of the group without metastasis and 70.4% of the group with metastasis (p = 0.001). Conclusion: The lymph node characteristics were associated with response to initial therapy and neck recurrence/persistence, confirming the importance of the analysis of these factors in risk stratification in a Brazilian population and its possible use to tailor initial staging and long term follow-up.

Atualização terapêutica no tratamento dos craniofaringiomas / Therapeutic update on the treatment of craniopharyngiomas

O craniofaringioma é uma neoplasia de natureza benigna, pouco frequente, responsável por 1 por cento a 3 por cento de todos os tumores intracranianos, sendo a mais frequente neoplasia intracraniana não neuroepitelial na criança. Geralmente o tumor é restrito à região selar e ao III ventrículo, mas, em decorrência da infiltração e frequente aderência ao sistema nervoso central, apresenta comportamento clínico muitas vezes desfavorável, sendo classificado pela Organização Mundial de Saúde (OMS) como grau I, caracterizado como tumor de baixo ou incerto potencial de malignização. As sequelas endocrinológicas ganham destaque devido ao importante impacto na qualidade de vida dos pacientes, na maioria das vezes crianças. O hipopituitarismo e a obesidade hipotalâmica são complicações frequentes, sendo o tratamento desse tumor um grande desafio para endocrinologistas e neurocirurgiões. A combinação da cirurgia, radioterapia e aplicação de drogas e radioisótopos intratumorais tem como objetivo maximizar as chances de cura e tentar minimizar as sequelas pós-operatórias, mas, mesmo assim, a recidiva ainda é frequente. A escolha da modalidade de tratamento mais adequado para os craniofaringiomas é uma decisão difícil e que deve sempre ser individualizada para cada paciente. Com o objetivo de explorar as múltiplas opções terapêuticas para o craniofaringioma, foi realizada revisão na literatura com ênfase nas possibilidades terapêuticas e complicações inerentes ao tratamento dessa patologia.

Craniopharyngioma is an uncommon benign neoplasm, accounting for 1 percent-3 percent of all intracranial tumors, and the most common non-neuroepithelial intracranial neoplasm in childhood. Usually, the tumor is confined to the sellar region and the third ventricle, but due to frequent infiltration and adherence to the central nervous system, it often has an unfavorable clinical behavior. Therefore, it is classified by the World Health Organization (WHO) as a tumor of low or uncertain malignant potential. Endocrine after effects, mainly hypothalamic hypopituitarism, obesity and diabetes insipidus are highlighted due to their important impact on the quality of life of patients, mostly children. Optimal treatment of this tumor is a major challenge for neurosurgeons and endocrinologists. The combination of surgery, radiation, and application of radioisotopes and intratumoral drugs, aims at maximizing the chances of cure with minimal complications. Yet, recurrence is still frequent. Choosing the best treatment modality for craniopharyngiomas is a difficult decision, and it should always be specific for each case. In order to explore the multiple therapeutic options for craniopharyngiomas, we reviewed the literature with emphasis on the therapeutic possibilities and complications inherent to the treatment of this disease.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14). The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5 percent and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up). Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014). The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

Avaliação da velocidade de onda de pulso aórtico em mulheres com gestação complicada por Diabetes Mellitus Gestacional / Assessment of aortic stiffness in women with gestational diabetes

Introdução: O diabetes mellitus gestacional (DMG) é uma complicação freqüente da gravidez que pode preceder o surgimento de diabetes mellitus tipo 2 (DM2) e estar relacionado com um risco aumentado de doença cardiovascular (DCV). A medida não-invasiva da velocidade de onda de pulso (VOP) é considerada como a melhor forma de investigar alterações da complacência arterial, um marcador pré-clínico de risco cardiovascular. Entretanto, a relação entre o DMG e o comportamento da VOP não está bem elucidada sendo apenas recentemente descrita. O objetivo deste estudo foi avaliar comparativamente a VOP em gestantes com DMG confirmado por teste oral de tolerância à glicose com 100g (TOTG), com um grupo pareado composto por gestantes consideradas saudáveis. Metodologia: Neste estudo casocontrole transversal, foram incluídas 24 gestantes com DMG e 27 gestantes de um grupo controle pareado. Foi considerado critério de exclusão do estudo a presença de passado de exposição a qualquer grau de intolerância à glicose. Todas gestantes foram avaliadas quanto a dados clínicos, demográficos e laboratoriais, além das medidas de VOP em territórios carótida-radial e carótida-femoral. As medidas de VOP foram realizadas por técnica de tonometria por aplanação com aparelho marca Complior®. Resultados: Os grupos apresentaram valores semelhantes de idade cronológica, idade gestacional, IMC e pressãoarterial (PA). Gestantes com DMG apresentaram valores de VOP em territórios periférico e aórtico equiparáveis aos observados no grupo controle: 8,3±0,8 vs. 8,5±1,0 m/s (p=0.40) e 7,2±0,9 vs. 7,3±1,2 m/s (p=0.79) respectivamente. Quando categorizadas em relação à mediana da VOP aórtica (7,3m/s), idade (p<0.001), PA diastólica (p=0.03) e freqüência cardíaca (p=0.02) se relacionaram com o aumento da VOP. Gestantes do grupo alvo com medidas da VOP aórtica acima da mediana apresentaram tendência a terem valores mais altos de glicemia 1 hora pós prandial (128,2±24.2 mg/dL vs 118,0±14.6 mg/dL, p=0,22) e controle glicêmico insatisfatório (p=0,09). Os valores da área sob a curva do TOTG foram semelhantes dentre as gestantes do grupo alvo não tendo relação com os valores de VOP. Conclusão: Apesar da hipótese de que o DMG pode ser fator de risco para DCV, gestantes com DMG não apresentam valores maiores de VOP em comparação a gestantes saudáveis. O período de exposição à hiperglicemia pode ter sido insuficiente para aumentar a rigidez arterial em gestantes com DMG.

Background: Gestational diabetes mellitus (GDM) may precede type 2 diabetes (T2DM) development and may be related to cardiovascular disease (CVD). Pulse wave velocity (PWV) measurement is the gold-standard non-invasive method to evaluate arterial stiffness, a preclinical cardiovascular risk marker. However, the relationship between PWV and GDM is not clear, and has only recently been investigated. The aim of this study was to evaluate aortic PWV in women with confirmed GDM through 100g oral glucose tolerance test (OGTT) in comparison to a matched control group of healthy pregnant women. Methods: This sectional case-control study included 24 women with GDM and 27 matched controls. Exclusion criteria included previous glucose impairment of any degree. Clinical, demographic and laboratory variables were obtained. Carotid-radial (peripheral) and carotid-femoral (aortic) PWV were measured by applanation tonometry with Complior® equipment. Results: Both groups had similar age, gestational age, body mass index, ethnicity, smoking status, and blood pressures (BP). Women with GDM had comparable peripheral and aortic PWV to controls: 8.3±0.8 vs. 8.5±1.0 m/s (p=0.40) and 7.2±0.9 vs. 7.3±1.2 m/s (p=0.79) respectively. When categorized according to the median value of aortic PWV (7.3m/s), age (p<0.001), diastolic BP (p=0.03) and heart rate (p=0.02) were associated with increased arterial stiffness. GDM women with PWV values above the median presented a trend towards higher 1-hour post-prandial glycemia (128.2±24.2 mg/dL vs. 118.0±14.6 mg/dL, p=0.22) and worse glycemic control (p=0.09). Also in the GDM group, the diagnostic OGTT area under the curve was similar in women with higher or lowers aortic PWV. Conclusion: Although GDM may be a risk factor for CVD development, women with GDM do not have higher peripheral or central arterial stiffness than healthy pregnant women. Time of exposure to hyperglycemia may have been insufficient to increase arterial stiffness in GDM women.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review / Tumor epitelial de células fusiformes com diferenciação thymus-like da tireoide (SETTLE): relato de caso e revisão da literatura

Spindle epithelial tumor with thymus-like element (SETTLE) is a rare malignant neoplasm of the thyroid, occurring predominantly in children, adolescents, and young adults. SETTLE usually presents itself as a thyroid mass, without metastases at diagnosis. It is believed to derive from branchial pouch or thymic remnant tissue showing primitive thymic differentiation. This article reports the clinical, cytological, histological and immunohistochemical features of a SETTLE in a 3-year-old girl. Microscopic exam revealed a nodular, highly cellular neoplasm displayed in the classic biphasic pattern, with mixture of prominent spindle cell component and a minor glandular component lined by mucinous or respiratory-type epithelium. The immunohistochemical study showed strong and diffuse positivity for pan-CK, vimentin and smooth muscle actin. The present case is the first SETTLE case reported in Brazil. To date, the patient described remains without evidence of recurrence or metastasis 5 years after surgery.

O tumor epitelial de células fusiformes com elemento thymus-like é uma rara neoplasia maligna da tireoide, ocorrendo predominantemente em crianças, adolescentes e adultos jovens. Habitualmente, esse tumor se apresenta como massa tireoideana, sem metástases ao diagnóstico. Acredita-se derivar de arco branquial ou tecido remanescente tímico, apresentando diferenciação tímica primitiva. Este artigo descreve os aspectos clínicos, citológicos, histológicos e imuno-histoquímicos de um caso de SETTLE diagnosticado em uma menina de 3 anos de idade. O aspecto microscópico encontrado no tumor foi de uma lesão nodular, hipercelular, disposta em aspecto bifásico clássico, com componente de células fusiformes, e de tecido glandular acompanhado por epitélio mucinoso e respiratório. O estudo imuno-histoquímico foi positivo para pan-CK, vimentina e actina de músculo liso. Esse caso é o primeiro relato de SETTLE no Brasil. A paciente descrita permanece sem evidência de doença em atividade cinco anos após o tratamento cirúrgico.