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Introdução: A deposição de cálcio junto aos folhetos valvares esta intimamente relacionada à fisiopatologia da estenose valvar aórtica degenerativa (EAD). A tomografia computadorizada com multidetectores (TCMD), além de possibilitar o delineamento tridimensional das estruturas cardíacas, permite a quantificação da intensidade da calcificação valvar. Atualmente, a relação entre a localização dos depósitos valvares de cálcio e a gravidade hemodinâmica na estenose aórtica permanece incerta. Objetivo: Avaliar se a topografia da calcificação valvar influencia a repercussão hemodinâmica na EAD. Métodos: Trata-se de estudo prospectivo, unicêntrico, incluindo 97 pacientes com EAD moderada ou importante. O escore de cálcio da valva aórtica foi calculado a partir da TCMD sem contraste. A topografia da calcificação valvar foi avaliada através de análise tomográfica específica com infusão de baixa dose de contraste endovenoso, objetivando uma detalhada segmentação anatômica dos planos valvares. A medida da atenuação, expressa em unidades Hounsfield (UH), foi utilizada para quantificar o conteúdo de cálcio na região central e periférica do plano valvar aórtico. Resultados: Pacientes com EAD importante apresentaram escore de cálcio valvar aórtico superior ao dos portadores de EAD moderada (3131 ± 1828 unidades Agatston [UA] e 1302 ± 846 UA, respectivamente; p < 0,001). Quanto à topografia da calcificação, pacientes com EAD importante exibiram atenuações significativamente maiores no centro do plano valvar do que em sua periferia (507,4 ± 181,7 UH vs. 449,8 ± 114,5 UH; p = 0,001). Inversamente, pacientes com EAD moderada apresentaram menor atenuação na região central do que na periferia valvar (308,7 ± 92,9 UH vs. 347,6 ± 84,2 UH, p < 0,001). A razão da atenuação centro/periferia também foi significativamente maior nos pacientes com EAD importante (1,14 ± 0,32 vs. 0,89 ± 0,13; p < 0,001), permanecendo significativamente associada à presença de EAD importante mesmo após ajuste para o grau subjacente de calcificação Resumo valvar. Conclusão: A gravidade da EAD parece resultar não apenas do grau de calcificação, mas também da localização dos depósitos valvares de cálcio / Introduction: The pathophysiology of degenerative aortic valve stenosis (AS) is intimately related to the development of calcific deposits in the valve structure. Multidetector computed tomography (MDCT), a reliable method to delineate the tridimensional heart geometry, has been shown to accurately quantify the global aortic valve calcium content. Currently, the relationship between calcium location and hemodynamic disease severity is poorly understood. Objective: The present prospective study was conducted to test the hypothesis of whether the location of valve calcification influences the functional severity of AS. Methods: Prospective, single-arm study including 97 patients with diagnosed moderate or severe AS. Aortic valve calcium score was calculated from nocontrast multidetector computed tomography (MDCT). \"Low-contrast- os \" MDCT images were acquired for segmentation of the cardiac anatomy, with the attenuation, expressed in Hounsfield units (HU), used to quantify the calcium content at the central and peripheral regions of the aortic valve zone. Results: The calcium score was higher among patients with severe AS compared to patients without severe AS (3131±1828 Agatston units [AU] vs. 1302±846 AU respectively; p < 0.001). Patients with severe AS had significantly higher attenuations at the center of the valve than at its periphery (507.4±181.7 HU vs. 449.8±114.5 HU; p=0.001). Conversely, patients without severe AS had lower attenuation at the center than at the periphery of the valve (308.7 ± 92.9 HU vs. 347.6±84.2 HU; p < 0.001). The center/periphery attenuation ratio was significantly higher for patients with severe AS than for those without severe disease (1.14±0.32 vs. 0.89 ± 0.13; p < 0.001), and remained significantly associated with the presence of severe AS even after adjusting for the underlying degree of valve calcification. Conclusion: The severity of degenerative aortic valve stenosis appears to result not only from the degree of calcification but also from the localization of the calcific deposits within the valve

Introdução: A deposição de cálcio junto aos folhetos valvares esta intimamente relacionada à fisiopatologia da estenose valvar aórtica degenerativa (EAD). A tomografia computadorizada com multidetectores (TCMD), além de possibilitar o delineamento tridimensional das estruturas cardíacas, permite a quantificação da intensidade da calcificação valvar. Atualmente, a relação entre a localização dos depósitos valvares de cálcio e a gravidade hemodinâmica na estenose aórtica permanece incerta. Objetivo: Avaliar se a topografia da calcificação valvar influencia a repercussão hemodinâmica na EAD. Métodos: Trata-se de estudo prospectivo, unicêntrico, incluindo 97 pacientes com EAD moderada ou importante. O escore de cálcio da valva aórtica foi calculado a partir da TCMD sem contraste. A topografia da calcificação valvar foi avaliada através de análise tomográfica específica com infusão de baixa dose de contraste endovenoso, objetivando uma detalhada segmentação anatômica dos planos valvares. A medida da atenuação, expressa em unidades Hounsfield (UH), foi utilizada para quantificar o conteúdo de cálcio na região central e periférica do plano valvar aórtico. Resultados: Pacientes com EAD importante apresentaram escore de cálcio valvar aórtico superior ao dos portadores de EAD moderada (3131 ± 1828 unidades Agatston [UA] e 1302 ± 846 UA, respectivamente; p < 0,001). Quanto à topografia da calcificação, pacientes com EAD importante exibiram atenuações significativamente maiores no centro do plano valvar do que em sua periferia (507,4 ± 181,7 UH vs. 449,8 ± 114,5 UH; p = 0,001). Inversamente, pacientes com EAD moderada apresentaram menor atenuação na região central do que na periferia valvar (308,7 ± 92,9 UH vs. 347,6 ± 84,2 UH, p < 0,001). A razão da atenuação centro/periferia também foi significativamente maior nos pacientes com EAD importante (1,14 ± 0,32 vs. 0,89 ± 0,13; p < 0,001), permanecendo significativamente associada à presença de EAD importante mesmo após ajuste para o grau subjacente de calcificação Resumo valvar. Conclusão: A gravidade da EAD parece resultar não apenas do grau de calcificação, mas também da localização dos depósitos valvares de cálcio / Introduction: The pathophysiology of degenerative aortic valve stenosis (AS) is intimately related to the development of calcific deposits in the valve structure. Multidetector computed tomography (MDCT), a reliable method to delineate the tridimensional heart geometry, has been shown to accurately quantify the global aortic valve calcium content. Currently, the relationship between calcium location and hemodynamic disease severity is poorly understood. Objective: The present prospective study was conducted to test the hypothesis of whether the location of valve calcification influences the functional severity of AS. Methods: Prospective, single-arm study including 97 patients with diagnosed moderate or severe AS. Aortic valve calcium score was calculated from nocontrast multidetector computed tomography (MDCT). \"Low-contrast- os \" MDCT images were acquired for segmentation of the cardiac anatomy, with the attenuation, expressed in Hounsfield units (HU), used to quantify the calcium content at the central and peripheral regions of the aortic valve zone. Results: The calcium score was higher among patients with severe AS compared to patients without severe AS (3131±1828 Agatston units [AU] vs. 1302±846 AU respectively; p < 0.001). Patients with severe AS had significantly higher attenuations at the center of the valve than at its periphery (507.4±181.7 HU vs. 449.8±114.5 HU; p=0.001). Conversely, patients without severe AS had lower attenuation at the center than at the periphery of the valve (308.7 ± 92.9 HU vs. 347.6±84.2 HU; p < 0.001). The center/periphery attenuation ratio was significantly higher for patients with severe AS than for those without severe disease (1.14±0.32 vs. 0.89 ± 0.13; p < 0.001), and remained significantly associated with the presence of severe AS even after adjusting for the underlying degree of valve calcification. Conclusion: The severity of degenerative aortic valve stenosis appears to result not only from the degree of calcification but also from the localization of the calcific deposits within the valve

Local invasion and lymph nodal spread impact in the outcome of Head and Neck squamous cell carcinoma (HNSCC) patients (pts). We determined CXCR1-5, CCR7 and CX3CR1 mRNA expression by means of RNAse protection assay in 98 HNSCC primary tumors and 91 adjacent mucosa and 26 metastatic lymph nodes, correlating this data with outcome. CXCL12 and CCL19/CCL21, ligands for CXCR4 and CCR7, were determined in 38 tumor fragments, 33 adjacent mucosas and 25 de metastatic lymph nodes, by means of Quantitative Real-Time PCR. Tumors presented higher CXCR1 (P=0.013), CXCR3 (P=0.008) and CXCR4 mRNA (P=0.025) expression as compared to mucosa. No correlations are observed neither lymph nodal status nor tumor size impacted on chemokine receptor expression. Metastatic lymph nodes expressed more CXCR4, CXCR5, CCR7 and CX3CR1 (P<0.0001) as compared to matched tumors. We found a longer overall survival (OS) (P=0.048) and a trend toward longer disease free survival (DFS) (P=0.074) in CX3CR1 negative (n=17) as compared to positive pts (n=21) only in oral subgroup. The same occurred for CCR7 negative oral SCC, in terms of OS (P=0.024) and DFS (P=0.049). We conclude that, of the chemokine receptors here studied, CCR7 and CX3CR1 mRNA expression seems to better reflect outcome in oral subsite only. In addition, CCL21, a CCR7 ligand mRNAs is more expressed in metastatic lymph nodes than tumors (P=0.059). Further studies are warranted to confirm these results. / Bone tissue alterations and vascular calcification (VC) are commonly found in patients with chronic renal failure (CKD). The importance of phosphorus (P) and parathyroid hormone (PTH) is not clear, yet. An in vitro study showed that inorganic phosphate was able to transform vascular smooth muscle cells (VSMC) into calcifying cells confirmed for up-expression of Runx2 in these cells. Besides, it has been demonstrated the in vivo expression of Runx2 in intimal and medial VSMC in calcified arteries of CKD patients. We evaluated the effect of phosphorus (P) and parathyroid hormone (PTH) on bone remodeling and on the expression of bone proteins (Runx2, Osteoprotegerin, type I Collagen, Osteocalcin, Osteopontin and NF?B) in aortic valve and heart in experimental uremia. Wistar rats were submitted to parathyroidectomy, nephrectomy (Nx) and continuous infusion of 1-34 rat PTH in physiologic or 5 times the normal values. The diet was identical, however the P content was low (LP: 0,2%) or high (HP: 1,2%). We performed biochemical, histomorphometric, imuno-histochemistry and RT-PCR analysis. Rats submitted to Nx developed renal failure. The P overload contributed to loss bone volume independent of uremia. Besides Nx animals that received high PTH doses bone loss was slight probably because of the anabolic effect of PTH, which was attenuated by the phosphorus overload toxic. VC was only observed in Nx animals that received high PTH doses independently of P overload. However, the P overload with physiologic PTH doses induced phenotypic changes in VSMC that was confirmed for the up-expression of Runx2 on aorta of these animals. The high concentrations of P and PTH promoted histological changes on expression of osteoprotegerin and type I Collagen in calcified arteries and heart. This study does not established ideal levels of PTH sufficient for the maintenance of the bone integrity and also to prevent VC when animal are submitted to different P overload.

INTRODUÇÃO: O objetivo deste estudo é determinar a correlação anatomopatológica das calcificações amorfas agrupadas diagnosticadas na mamografia digital de campo total, ou seja, das calcificações suspeitas mais tênues, uma vez que houve aumento da caracterização de calcificações na mamografia digital. MÉTODOS: Estudo retrospectivo baseado nos laudos mamográficos classificados como categoria BI-RADS 4 no primeiro ano de introdução da técnica digital, com análise dos diagnósticos anatomopatológicos das microcalcificações amorfas agrupadas submetidas à biópsia de fragmento assistida à vácuo no serviço. Calculou-se: os achados anatomopatológicos que se associaram ao achado radiológico de microcalcificações amorfas agrupadas e o valor preditivo positivo destas calcificações biopsiadas. RESULTADOS: Dos 219 achados por microcalcificações amorfas agrupadas, 78 foram submetidos à biópsia de fragmento assistida à vácuo com seguimento conhecido ou cirurgia subsequente. O diagnóstico anatomopatológico correspondeu a oito (10%) casos malignos, 36 (46%) casos benignos, e 34 (44%) diagnósticos de lesões de risco, das quais oito (10%) do subgrupo cicatriz radiada/lesões papilíferas (sete cicatrizes radiadas e um papiloma) e 26 (33%) do subgrupo atipias/ neoplasias lobulares, correspondendo a 14 (18%) hiperplasias ductais atípicas, quatro (5%) neoplasias lobulares e oito (10%) lesões de células colunares com atipia (atipia epitelial plana). A ampliação cirúrgica foi recomendada para as lesões com potencial incerto de malignidade à biópsia e realizada em 65% do subgrupo atipias/neoplasias lobulares, com taxa de subestimação nula (0/18). O tempo médio de seguimento das pacientes com diagnóstico benigno ou de lesão de risco foi 22 meses. CONCLUSÕES: Um terço das microcalcificações amorfas agrupadas em mamografia digital de campo total corresponderam a lesões precursoras representadas pelas atipias (ductais e colunares) e neoplasias lobulares. Essas lesões se associaram às calcificações amorfas agrupadas numa proporção de cerca de 3:1 em relação às lesões malignas, cujo VPP 3 foi 10% / PURPOSE: To determine the anatomopathological correlation of grouped amorphous calcifications (the most tenuous of suspicious calcifications) disclosed on full-field digital mammography, given the enhanced characterization of calcifications provided by digital mammography. METHODS: A retrospective study of mammographic reports classified as BI-RADS® category 4 at a private diagnostic service specialized in breast imaging was carried out on exams performed during the first year of introducing the digital technique. The investigation entailed analysis of the anatomopathological diagnoses of BI-RADS® category 4 for grouped amorphous microcalcifications submitted to vacuum-assisted breast biopsy (VABB). Anatomopathological findings correlated to this radiological finding were determined and positive predictive value of these calcifications submitted to biopsy (PPV 3) was calculated. RESULTS: Of the 219 findings of grouped amorphous microcalcifications, 78 were submitted to VABB with known follow-up or subsequent surgery. The anatomopathological results included eight (10%) malignant cases, 36 (46%) benign cases and 34 (44%) diagnoses of high-risk lesions, eight of which belonged to the radial scar/papillary lesion subgroup (seven radial scars and one papilloma) and 26 (33% of all cases) to the atypia/lobular neoplasia subgroup, comprising 14 atypical ductal hyperplasias, four lobular neoplasias and eight flat epithelial atypia. Extended surgery was recommended for lesions with uncertain malignant potential at biopsy and performed in 65% of the atypia/lobular neoplasia subgroup, with an underestimation rate of zero (0/18). Mean follow-up time of patients diagnosed with benign or high-risk lesions was 22 months. CONCLUSIONS: One-third of grouped amorphous calcifications on full-field digital mammography corresponded to precursory lesions in the form of atypia (ductal and columnar) or lobular neoplasias. These lesions were associated to grouped amorphous calcifications at a ratio of 3:1 compared to malignant lesions,whose PPV 3 was 10%

INTRODUÇÃO: O objetivo deste estudo é determinar a correlação anatomopatológica das calcificações amorfas agrupadas diagnosticadas na mamografia digital de campo total, ou seja, das calcificações suspeitas mais tênues, uma vez que houve aumento da caracterização de calcificações na mamografia digital. MÉTODOS: Estudo retrospectivo baseado nos laudos mamográficos classificados como categoria BI-RADS 4 no primeiro ano de introdução da técnica digital, com análise dos diagnósticos anatomopatológicos das microcalcificações amorfas agrupadas submetidas à biópsia de fragmento assistida à vácuo no serviço. Calculou-se: os achados anatomopatológicos que se associaram ao achado radiológico de microcalcificações amorfas agrupadas e o valor preditivo positivo destas calcificações biopsiadas. RESULTADOS: Dos 219 achados por microcalcificações amorfas agrupadas, 78 foram submetidos à biópsia de fragmento assistida à vácuo com seguimento conhecido ou cirurgia subsequente. O diagnóstico anatomopatológico correspondeu a oito (10%) casos malignos, 36 (46%) casos benignos, e 34 (44%) diagnósticos de lesões de risco, das quais oito (10%) do subgrupo cicatriz radiada/lesões papilíferas (sete cicatrizes radiadas e um papiloma) e 26 (33%) do subgrupo atipias/ neoplasias lobulares, correspondendo a 14 (18%) hiperplasias ductais atípicas, quatro (5%) neoplasias lobulares e oito (10%) lesões de células colunares com atipia (atipia epitelial plana). A ampliação cirúrgica foi recomendada para as lesões com potencial incerto de malignidade à biópsia e realizada em 65% do subgrupo atipias/neoplasias lobulares, com taxa de subestimação nula (0/18). O tempo médio de seguimento das pacientes com diagnóstico benigno ou de lesão de risco foi 22 meses. CONCLUSÕES: Um terço das microcalcificações amorfas agrupadas em mamografia digital de campo total corresponderam a lesões precursoras representadas pelas atipias (ductais e colunares) e neoplasias lobulares. Essas lesões se associaram às calcificações amorfas agrupadas numa proporção de cerca de 3:1 em relação às lesões malignas, cujo VPP 3 foi 10% / PURPOSE: To determine the anatomopathological correlation of grouped amorphous calcifications (the most tenuous of suspicious calcifications) disclosed on full-field digital mammography, given the enhanced characterization of calcifications provided by digital mammography. METHODS: A retrospective study of mammographic reports classified as BI-RADS® category 4 at a private diagnostic service specialized in breast imaging was carried out on exams performed during the first year of introducing the digital technique. The investigation entailed analysis of the anatomopathological diagnoses of BI-RADS® category 4 for grouped amorphous microcalcifications submitted to vacuum-assisted breast biopsy (VABB). Anatomopathological findings correlated to this radiological finding were determined and positive predictive value of these calcifications submitted to biopsy (PPV 3) was calculated. RESULTS: Of the 219 findings of grouped amorphous microcalcifications, 78 were submitted to VABB with known follow-up or subsequent surgery. The anatomopathological results included eight (10%) malignant cases, 36 (46%) benign cases and 34 (44%) diagnoses of high-risk lesions, eight of which belonged to the radial scar/papillary lesion subgroup (seven radial scars and one papilloma) and 26 (33% of all cases) to the atypia/lobular neoplasia subgroup, comprising 14 atypical ductal hyperplasias, four lobular neoplasias and eight flat epithelial atypia. Extended surgery was recommended for lesions with uncertain malignant potential at biopsy and performed in 65% of the atypia/lobular neoplasia subgroup, with an underestimation rate of zero (0/18). Mean follow-up time of patients diagnosed with benign or high-risk lesions was 22 months. CONCLUSIONS: One-third of grouped amorphous calcifications on full-field digital mammography corresponded to precursory lesions in the form of atypia (ductal and columnar) or lobular neoplasias. These lesions were associated to grouped amorphous calcifications at a ratio of 3:1 compared to malignant lesions,whose PPV 3 was 10%

Local invasion and lymph nodal spread impact in the outcome of Head and Neck squamous cell carcinoma (HNSCC) patients (pts). We determined CXCR1-5, CCR7 and CX3CR1 mRNA expression by means of RNAse protection assay in 98 HNSCC primary tumors and 91 adjacent mucosa and 26 metastatic lymph nodes, correlating this data with outcome. CXCL12 and CCL19/CCL21, ligands for CXCR4 and CCR7, were determined in 38 tumor fragments, 33 adjacent mucosas and 25 de metastatic lymph nodes, by means of Quantitative Real-Time PCR. Tumors presented higher CXCR1 (P=0.013), CXCR3 (P=0.008) and CXCR4 mRNA (P=0.025) expression as compared to mucosa. No correlations are observed neither lymph nodal status nor tumor size impacted on chemokine receptor expression. Metastatic lymph nodes expressed more CXCR4, CXCR5, CCR7 and CX3CR1 (P<0.0001) as compared to matched tumors. We found a longer overall survival (OS) (P=0.048) and a trend toward longer disease free survival (DFS) (P=0.074) in CX3CR1 negative (n=17) as compared to positive pts (n=21) only in oral subgroup. The same occurred for CCR7 negative oral SCC, in terms of OS (P=0.024) and DFS (P=0.049). We conclude that, of the chemokine receptors here studied, CCR7 and CX3CR1 mRNA expression seems to better reflect outcome in oral subsite only. In addition, CCL21, a CCR7 ligand mRNAs is more expressed in metastatic lymph nodes than tumors (P=0.059). Further studies are warranted to confirm these results. / Bone tissue alterations and vascular calcification (VC) are commonly found in patients with chronic renal failure (CKD). The importance of phosphorus (P) and parathyroid hormone (PTH) is not clear, yet. An in vitro study showed that inorganic phosphate was able to transform vascular smooth muscle cells (VSMC) into calcifying cells confirmed for up-expression of Runx2 in these cells. Besides, it has been demonstrated the in vivo expression of Runx2 in intimal and medial VSMC in calcified arteries of CKD patients. We evaluated the effect of phosphorus (P) and parathyroid hormone (PTH) on bone remodeling and on the expression of bone proteins (Runx2, Osteoprotegerin, type I Collagen, Osteocalcin, Osteopontin and NF?B) in aortic valve and heart in experimental uremia. Wistar rats were submitted to parathyroidectomy, nephrectomy (Nx) and continuous infusion of 1-34 rat PTH in physiologic or 5 times the normal values. The diet was identical, however the P content was low (LP: 0,2%) or high (HP: 1,2%). We performed biochemical, histomorphometric, imuno-histochemistry and RT-PCR analysis. Rats submitted to Nx developed renal failure. The P overload contributed to loss bone volume independent of uremia. Besides Nx animals that received high PTH doses bone loss was slight probably because of the anabolic effect of PTH, which was attenuated by the phosphorus overload toxic. VC was only observed in Nx animals that received high PTH doses independently of P overload. However, the P overload with physiologic PTH doses induced phenotypic changes in VSMC that was confirmed for the up-expression of Runx2 on aorta of these animals. The high concentrations of P and PTH promoted histological changes on expression of osteoprotegerin and type I Collagen in calcified arteries and heart. This study does not established ideal levels of PTH sufficient for the maintenance of the bone integrity and also to prevent VC when animal are submitted to different P overload.