Recurrence and mortality prognostic factors in childhood adrenocortical tumors: Analysis from the Brazilian National Institute of Cancer experience.

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.

Nonobese Young Females with Polycystic Ovary Syndrome have Nutritive Microvascular Dysfunction: A Pilot Study.

OBJECTIVE: To investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables. METHODS: Fourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/m2) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCVmax), and time taken to reach RBCVmax (TRBCVmax). RESULTS: Subjects with PCOS had lower RBCV and higher TRBCVmax compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, P<.01) and (5 [5-6] vs. 4 [3-5] s, P<.05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCVmax (ρ = -0.49, P<.05) and to TRBCVmax (ρ = 0.41, P<.05). SHBG correlated with RBCVmax (ρ = 0.52, P<.01) while estradiol (E2) levels correlated with RBCV (ρ = 0.80, P<.001) and RBCVmax (ρ = 0.46, P<.05). CONCLUSION: Microvascular dysfunction characterized by reduced RBCVmax and prolonged TRBCVmax was present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction.

The role of metabolic syndrome components and adipokines in insulin resistance in prepubertal children.

OBJECTIVE: Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children. METHODS: We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression. RESULTS: There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05). CONCLUSION: Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

RELATIONS BETWEEN ASTHMA AND OBESITY: AN ANALYSIS OF MULTIPLE FACTORS.

OBJECTIVE: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. METHODS: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. RESULTS: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. CONCLUSIONS: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations.

Abstract. OBJECTIVE: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. MATERIALS AND METHODS: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. RESULTS: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. CONCLUSION: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

OBJETIVO: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. MATERIAIS E MÉTODOS: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. RESULTADOS: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. CONCLUSÃO: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

Microcirculation, Adiposity, and Traditional and Emerging Cardiovascular Risk Factors in Prepubertal Children.

PURPOSE: Previous studies have shown that microvascular dysfunction (MD) is associated with a number of cardiovascular risk factors, including obesity. Few studies have assessed microvascular reactivity in children, and in most of these, results were confounded by the effects of puberty. Our aim was to establish whether MD is already present in obese prepubertal children. METHODS: This cross-sectional study included 52 obese, 18 overweight, and 28 eutrophic children, with a mean ± standard deviation age of 7.44 ± 1.22 years. We evaluated cardiovascular risk factors and nutritive microvascular function by using nailfold dynamic videocapillaroscopy and determined functional capillary density (FCD), red blood cell velocity at resting conditions (RBCV) and at peak (RBCVmax), and time to reach peak velocity during the post-occlusive reactive hyperemic response following 1 minute ischemia. RESULTS: On univariate analysis, differences in microvascular reactivity were not observed among the groups. Obese and overweight children had significantly higher scores than eutrophic children for the following parameters: body mass index, waist circumference, waist-to-height ratio, mean arterial pressure, homeostasis model assessment for insulin resistance, levels of insulin, leptin, glucose, triglycerides, total cholesterol, uric acid, and C-reactive protein. Multivariate analysis demonstrated the association between metabolic, anthropometric, and microvascular variables, stratified according to the degree of adiposity and body fat distribution. CONCLUSIONS: Univariate analysis did not show any difference in microvascular reactivity between groups but, by testing these variables by multivariate means, we noticed a common and direct variation between cardiovascular/metabolic risk factors and microvascular reactivity occurring early in life.

Relations between asthma and obesity: an analysis of multiple factors / Relações entre asma e obesidade: análise de múltiplos fatores

ABSTRACT Objective: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range. Methods: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected. Results: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively. Conclusions: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

RESUMO Objetivo: A asma e a obesidade são doenças prevalentes e inter-relacionadas. Na população pediátrica, o efeito da inflamação sistêmica associada à obesidade, levando à inflamação das vias aéreas, é controverso. Nosso objetivo foi comparar padrões inflamatórios, clínicos e espirométricos entre crianças obesas e aquelas com peso normal. Métodos: Setenta e nove meninos e meninas de 6‒10 anos de idade foram selecionados e divididos em quatro grupos: asmáticos obesos, asmáticos não obesos, não asmáticos obesos e não asmáticos não obesos. Além de dados clínicos e antropométricos, todas as crianças foram submetidas a espirometria e testes cutâneos para alérgenos inalantes. Também foram coletadas amostras de sangue para dosagem de citocinas e adipocinas. Resultados: Obesos asmáticos tiveram um controle significativamente pior da asma do que os não obesos (RP 4,9; IC95% 1,1‒22,1), independentemente do sexo, atividade física e atopia. Não foram observadas diferenças nos níveis de espirometria, citocinas Th1 e Th2 e adipocinas entre os quatro grupos. Os testes cutâneos foram positivos em 81,8 e 80% dos não obesos asmáticos e obesos asmáticos, respectivamente. Conclusões: O grau de controle da asma foi significativamente menor no grupo obeso, apesar de não ter havido diferenças nos achados espirométricos. Esse resultado sugere que fatores extrapulmonares podem ser responsáveis por esse perfil sintomático. A alta positividade do teste cutâneo nos dois grupos, considerado um bom marcador de atopia, demonstrou o componente atópico como preponderante na gênese da asma, tanto em crianças com obesidade quanto naquelas com peso normal.

Decreased serum inhibin B/FSH ratio as a marker of Sertoli cell function in male survivors after chemotherapy in childhood and adolescence.

OBJECTIVE: Inhibin B produced by Sertoli cells may be an important marker of seminiferous tubule function in patients treated with chemotherapy (CT). The aim of this study was to evaluate the inhibin B/FSH ratio to detect male gonadal dysfunction in cancer survivors treated in childhood and adolescence. PATIENTS: Twenty-one male patients (group A) treated with 6-10 courses of CT for Hodgkin's disease during childhood and adolescence were examined 3-11 years after the conclusion of treatment. Twenty healthy young men (18-23 years old) were used as controls (group B). METHODS: Serum samples for the determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), sex hormone-binding globulin (SHBG) and semen for analysis were collected. RESULTS: The median testicular volume of patients of group A was lower than those of group B (p = 0.001) and a positive correlation was found between testicular size and sperm count (r = -0.5, p = 0.01). Semen analysis revealed azoospermia in 11 patients, severe oligospermia in four and normal sperm count in three. No significant difference was found in the median of T, LH, SHBG, inhibin B concentrations and T/LH ratio between the groups. Serum inhibin B was correlated with the serum FSH levels (r = -0.5, p = 0.02). Median FSH was significantly higher (p = 0.0001), and median inhibin B/FSH ratio was significantly lower in group A than in controls (p = 0.0002), but the inhibin B/FSH ratio was higher in the patients with normal sperm count than in those with oligospermia (p = 0.00004). CONCLUSIONS: These results show that the cytotoxic effects of CT cause severe damage to the germinal epithelium with subtle effects on Sertoli cells. To assess Sertoli cell function in men with primary testicular damage after treatment with CT in childhood and adolescence, the inhibin B level needs to be interpreted in the context of the circulating FSH, especially when normal FSH levels are observed.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations / A ultrassonografia como método de avaliação da distribuição da gordura abdominal em crianças pré-púberes obesas e sua relação com alterações metabólicas

Abstract Objective: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. Materials and Methods: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. Results: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. Conclusion: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

Resumo Objetivo: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. Materiais e Métodos: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. Resultados: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. Conclusão: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

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

Craniopharyngioma is an uncommon benign neoplasm, accounting for 1%-3% 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% 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.

Thyroid spindle epithelial tumor with thymus-like differentiation (SETTLE): case report and review.

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.

[Cut-off point for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established from Receiver Operating Characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children]. / Ponto de corte do índice Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) avaliado pela curva Receiver Operating Characteristic (ROC) na detecção de síndrome metabólica em crianças pré-púberes com excesso de peso.

OBJECTIVE: To establish, among the cut-off values for the homeostatic model assessment for insulin resistance index (HOMA-IR) cited in the literature, the best in identifying metabolic syndrome (MS) in obese and overweight children. METHODS: A total of 106 pre-pubertal children were studied. The definition of MS was adapted from that of the International Diabetes Federation. For each cut-off values for HOMA-IR, it was estimated sensibility and specificity for MS. A receiver operating characteristic (ROC) curve was generated using these values. RESULTS: The study included 106 obese (37 girls and 69 boys) and 34 overweight (19 girls and 15 boys) children aged 6,5 +/- 2,3 years. The accuracy of the ROC curve was 72%, and the best cut-off value for HOMAIR was 2,5, with sensitivity of 61% and specificity of 74%. CONCLUSIONS: HOMA-IR may be useful to detect MS and the cut-off 2,5 seems to be the best in obese and overweight pre-pubertal children.

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.

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.

Ponto de corte do índice Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) avaliado pela curva Receiver Operating Characteristic (ROC) na detecção de síndrome metabólica em crianças pré-púberes com excesso de peso / Cut-off point for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established from Receiver Operating Characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children

OBJETIVO: Estabelecer, entre os pontos de corte do índice homeostatic model assessment for insulin resistance (HOMA-IR), citados na literatura, o melhor em identificar a síndrome metabólica (SM) em crianças com obesidade e sobrepeso. MÉTODOS: Foram estudadas 140 crianças pré-púberes. A definição de SM foi adaptada da International Diabetes Federation. Para cada ponto de corte de HOMA-IR foram estimados sensibilidade e especificidade, tomandose como desfecho a SM. Uma curva receiver operating characteristic (ROC) foi construída com estes valores. RESULTADOS: O grupo estudado constituiu-se de 106 crianças com obesidade (37 meninas e 69 meninos) e 34 com sobrepeso (19 meninas e 15 meninos), média de idade 6,5 ± 2,3 anos. A acurácia da curva ROC foi 72 por cento, e o melhor ponto de corte foi 2,5, com sensibilidade 61 por cento e especificidade 74 por cento. CONCLUSÃO: O índice HOMA-IR pode ser útil para detectar a SM, e o ponto de corte 2,5 mostrou-se o melhor para crianças pré-púberes com obesidade e sobrepeso.

OBJECTIVE: To establish, among the cut-off values for the homeostatic model assessment for insulin resistance index (HOMA-IR) cited in the literature, the best in identifying metabolic syndrome (MS) in obese and overweight children. METHODS: A total of 106 pre-pubertal children were studied. The definition of MS was adapted from that of the International Diabetes Federation. For each cut-off values for HOMA-IR, it was estimated sensibility and specificity for MS. A receiver operating characteristic (ROC) curve was generated using these values. RESULTS: The study included 106 obese (37 girls and 69 boys) and 34 overweight (19 girls and 15 boys) children aged 6,5 ± 2,3 years. The accuracy of the ROC curve was 72 percent, and the best cut-off value for HOMAIR was 2,5, with sensitivity of 61 percent and specificity of 74 percent. CONCLUSIONS: HOMA-IR may be useful to detect MS and the cut-off 2,5 seems to be the best in obese and overweight pre-pubertal children.

Espectro ultra-sonográfico no hiperandrogenismo: ovários policísticps x ovários multicísticos / Sonographic spectrum in the hyperandrogenism: polycystic ovaries x multicystic ovaries

O objetivo deste estudo foi determinar as principais diferenças clínicas e ultra-sonográficas entre ovários policísticos (OP) e multicísticos (OM). Selecionamos 39 mulheres com hiperandrogenismo e/ou anovulaçao crônica de causa nao definida (HACND) e realizamos dosagem dos androgênios, hormônio luteotrófico (LH), hormônio folículo estimulante (FSH) e ultra-sonografia pélvica (USG). Na ultra-sonografia pélvica, quando encontramos dez ou mais cistos, classificamos em: OP - volume ovariano maior do que 10cm3 ou quando o estroma era hiperecogênico e OM - volume ovariano menor do que 10 cm3 ou ausência da intensidade do eco do estroma. Em quatro pacientes, a USG foi considerada normal. Nas demais, utilizando o parâmetro estroma, 27 pacientes apresentavam OP e 8 OM. Comparando OP x OM, o volume ovariano e a freqüência de ciclos irregulares foi maior no OP (p<0.05). Quando utilizamos o parâmetro volume ovariano, 21 pacientes apresentavam OP e 14 OM. Comparando os dois grupos, a freqüência de ciclos irregulares foi maior no OP e encontramos correlaçao entre testosterona e volume ovariano (r=0.36, p<0.05). Portanto, consideramos que a classificaçao entre OP e OM, independente do parâmetro ulttra-sonográfico utilizado - volume ovariano ou estroma -, pode representar um amplo espectro clínico e hormonal presente em mulheres com HACND e por isso deveria ser utilizada como rotina.

Estudo da função gonadal de pacientes com Doença de Hodgkin tratados com o esquema C-MOPP/ABV ou "Híbrido modificado"

Este trabalho propô-se a estudar a função gonadal de 21 pacientes adultos do sexo masculino, com idades entre 17 e 23 anos (18 1,99), sobreviventes de Doença de Hodgkin (grupo A), tratados com quimiotrapia na infância e adolescência, com seis ou mais ciclos do esquema C-MOPP/ABV ou "híbrido modificado" (ciclofosfamida, vincristina, prednisona, adriamicina, blenoxane, vimblastina). A média da idade no diagnóstico foi de 11,3 ± 4,01 anos, 14 eram impúberes e 7 já haviam iniciado a puberdade. O intervalo de tempo entre o início do tratamento e o estudo foi de 3 a 11 anos (7,42±2,82) e, todos se encontravam no estágio puberal V de Tanner quando foram avaliados, tendo a puberdade evoluido normalmente. Estabelecemos como grupo controle (grupo B) 20 indivíduos do sexo masculino com idades entre 18 e 25 anos (20,95±1,53). Avaliamos o volume testicular, os níveis basais de testosterona total (TT), índice de testosterona livre (ITL), SHBG, prolactina (PRL), FSH, LH, inibina B (IB), relações TT/LH, IB/FSH e resposta do FSH e do LH após estímulo com GnRH e espermograma. A média do volume testicular foi menor (p=0,001) nos pacientes (15,42±5,46ml) do que nos controles (21,0±3,47ml). Não encontramos diferença significativa na média dos níveis de TT, ITL, SHBG, PRL, IB, LH e relação TT/LH entre os grupos A e B. A mediana da relação IB/FSH foi menor (P=0,0002) nos pacientes 31,01 (3,8-267,9) do que nos controles 142,10 (47,6767,3). Os níveis de FSH e inibina B foram significativamente e inversamente relacionados (r=-0,50,p=0,02) nos pacientes do grupo A. Amediana dos níveis basais do FSH 5,4UI/ml (1,2-22,4 UI/ml) e a média do valor máximo do FSH (18,34±14,7 ui/mL) e do LH (30,99±20,88 UI/mL) após estímulo com GnRH do grupo A, foi maior do que a mediana dos níveis basais do FSH 1,5 UI/mL (0,3-35 UI/mL), média do valor máximo do FSH (5,58±1,98 UI/mL) e do LH (13,75±5,16 UI/mL) do grupo B, com significância de: p=0,0001;p=0,0002, respectivamente. Observamos azoospermia em 11, oligospermia em 4 e espermograma normal em 3 pacientes. Apenas 1 paciente recuperou a espermatogênese após 11 anos do tratamento. Concluimos que o esquema C-MOPP/ABV quando administrado em crianças e adolescentes causa dano ao epitélio germinativo e discreta disfunção das células de Leydig e de Sertoli, entretanto é necessário um tempo longo de acompanhamento para se observar possível recuperação da função gonadal.

The aim of this study was to asses the gonadal function in 21 adult (group A) male patients, with Hodgkins’disease, who had received combination chemotherapy consisting of C-MOPP/ABV hybrid program (cyclophosphamide, vincristine, procarbazine, doxorubicin, bleomycin, vinblastine). Twenty healthy young men were the control group (group B). The age of the patients at the time of the study was 18,7±1,99 years, and at the time of chemotherapy was 1l, 33±4,01 years. At that time 14 patients were prepubertal and 7 were pubertal and at the time of the study all were Tanner V. The mean interval from the treatment until the study was 7,42±2,82 years. Puberty had progressed normally in all patients. We evaluated testicular size, total testosterone (TT), SHBG, free androgen index (F AI), prolactin (PRL), FSH, LH, Inhibin B (IB) levels, testosterone/LH (TILH), Inhibin B/FSH (IB/FSH) ratio, FSH and LH after GnRH test and sperm counts. The mean testicular volume was 15,42±5,46 ml and 21,0±3,47 ml for patients and controls (p= 0,001) respectively. We found no significant differences in TT, F AI, SHBG, PRL, IB, LH and TT/LH ratio between patients and controls. The median IB/FSH ratio in the patients was lower (p=0,0002) than in the controls (31,01 vs 142,10). FSH levels and inhibin B were significantly and inversely correlated (r= -0,50; p=0,02). We detected an appreciable difference in peak FSH levels (p=0,002) and in peak LH levels (p= 0,0002). The results of semen analyses were: 11 patients had azoospermIa, 4 oligospermia and 3 patients had a normal semem analysis. Only one patient had recovered fertility, with normalization of sperm count 11 years following treatment. These results suggest that C-MOPP/ABV hybrid program causes damage to the germinal ephithelium even when given during prepubertal and adolescent age. Cytotoxic chemotherapy-induced testicular damage is associated with subtle Sertoli and Leydig cells dysfunction, and long-term follow up is necessary to ascertain if gonadal function will recover.