Carcinoma de seio maxilar: análise de dez casos

OBJETIVO: Avaliar o papel, principalmente da tomografia computadorizada, no estadiamento dos carcinomas dos seios maxilares. MATERIAIS E MÉTODOS: Foram analisados dez casos de carcinoma diagnosticados e tratados pelos Departamentos de Diagnóstico por Imagem e Cirurgia de Cabeça e Pescoço do Hospital Heliópolis, São Paulo, SP, entre 1988 e 2002. RESULTADOS: Nove pacientes tiveram extensão tumoral para a bochecha, oito para o espaço mastigador, sete para o assoalho da boca e palato duro, cinco para a fossa pterigóide, cinco para a órbita, três para o etmóide e um para a base do crânio. Três pacientes foram classificados como T3 e sete, como T4. Dois tinham metástases linfonodais no momento da apresentação inicial, os quais pertenciam ao estágio T4. Todos os casos foram confirmados com exame histopatológico. CONCLUSÃO: A análise precisa da extensão local e disseminação tumoral fornecida pela tomografia computadorizada e ressonância magnética desempenha papel importante no planejamento cirúrgico, influenciando, também, na conduta terapêutica e prognóstico.

Frequent nitric oxide synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression.

An increased expression of nitric oxide synthase (NOS) has been observed in human colon carcinoma cell lines as well as in human gynecological, breast, and central nervous system tumors. This observation suggests a pathobiological role of tumor-associated NO production. Hence, we investigated NOS expression in human colon cancer in respect to tumor staging, NOS-expressing cell type(s), nitrotyrosine formation, inflammation, and vascular endothelial growth factor expression. Ca2+-dependent NOS activity was found in normal colon and in tumors but was significantly decreased in adenomas (P < 0.001) and carcinomas (Dukes' stages A-D: P < 0.002). Ca2+-independent NOS activity, indicating inducible NOS (NOS2), is markedly expressed in approximately 60% of human colon adenomas (P < 0.001 versus normal tissues) and in 20-25% of colon carcinomas (P < 0.01 versus normal tissues). Only low levels were found in the surrounding normal tissue. NOS2 activity decreased with increasing tumor stage (Dukes' A-D) and was lowest in colon metastases to liver and lung. NOS2 was detected in tissue mononuclear cells (TMCs), endothelium, and tumor epithelium. There was a statistically significant correlation between NOS2 enzymatic activity and the level of NOS2 protein detected by immunohistochemistry (P < 0.01). Western blot analysis of tumor extracts with Ca2+-independent NOS activity showed up to three distinct NOS2 protein bands at Mr 125,000-Mr 138,000. The same protein bands were heavily tyrosine-phosphorylated in some tumor tissues. TMCs, but not the tumor epithelium, were immunopositive using a polyclonal anti-nitrotyrosine antibody. However, only a subset of the NOS2-expressing TMCs stained positively for 3-nitrotyrosine, which is a marker for peroxynitrite formation. Furthermore, vascular endothelial growth factor expression was detected in adenomas expressing NOS2. These data are consistent with the hypothesis that excessive NO production by NOS2 may contribute to the pathogenesis of colon cancer progression at the transition of colon adenoma to carcinoma in situ.

Tumores neuroendócrinos do pulmão: principais achados radiológicos em uma série de 22 casos com confirmação anatomopatológica

OBJETIVO: Descrever os principais achados de imagem em uma série de casos de tumores neuroendócrinos primários do pulmão (TNPs), destacando as alterações na tomografia computadorizada. MATERIAIS E MÉTODOS: Exames de 22 pacientes (12 homens, idade média de 60 anos) avaliados nos últimos cinco anos em nosso serviço, com confirmação histopatológica, foram retrospectivamente revistos por dois médicos radiologistas e os achados foram descritos em consenso, focando as alterações tomográficas. RESULTADOS: Descrevemos 5 carcinoides típicos, 3 carcinoides atípicos, 3 carcinomas neuroendócrinos de grandes células (CNGCs) e 11 cânceres pulmonares de pequenas células (CPPCs). Apenas um carcinoide típico apresentou aspecto característico de nódulo endobrônquico central com atelectasia pulmonar distal, enquanto os demais foram nódulos ou massas pulmonares. Os carcinoides atípicos eram massas pulmonares periféricas e heterogêneas. Um CNGC era massa periférica delimitada e homogênea, enquanto os demais eram mal delimitados e heterogêneos. Os 11 CPPCs eram massas centrais, infiltrativas e heterogêneas, com alterações pleuropulmonares secundárias. Calcificações estavam ausentes nos CNGCs e CPPCs. Metástases foram vistas inicialmente ou no seguimento de todos os CNGCs e CPPCs. CONCLUSÃO: Apesar de alguns aspectos semelhantes nos exames de imagem, os achados radiológicos, quando integrados às informações clínicas, podem constituir critérios importantes na diferenciação dos tipos histológicos de TNPs.

Pancreatic adenocarcinoma: the impact of preneoplastic lesion pattern on survival.

Pancreatic adenocarcinoma is associated with a very poor prognosis, characterized with a 5-year survival rate of only 5%. Surgery is the only curative treatment for selected patients. Nevertheless, recurrence is very frequent. Identifying prognostic factors is thus warranted. Like numerous other tumors, adenocarcinomas are preceded by preneoplastic lesions. The role and the impact of these lesions remain unclear. This study aimed to assess the impact of the preneoplastic lesion pattern and histo-morphological features, on survival after pancreatic resection. Thirty-five patients who underwent pancreatic resection for pancreatic adenocarcinoma were identified from a prospective database of a single center, between 2003 and 2008. We considered demographics, tumor characteristics and type of treatment. The major outcome was survival. Analyzes were separated into two groups, according to the preneoplastic lesions: Pancreatic intraepithelial neoplasia (PanIN)-related carcinomas and intracanalar papillary mucinous neoplasia (IPMN)-related carcinomas. The former were more frequent, accounting for 63% (22/35). Moreover, they displayed more aggressive features, with a higher tumor stage (p = 0.01) and higher rate of positive lymph nodes (p = 0.019). Lymphatic (p = 0.009) and perinervous (p = 0.019) invasions were also more frequent. Survival was negatively influenced by PanIN preneoplastic lesions (p = 0.015), T3-4 tumor stage (p = 0.038), positive lymph nodes (p = 0.044), lymphatic (p = 0.019) and vascular (p = 0.029) invasions. Pancreatic adenocarcinoma displays different behavior according to its preneoplastic lesion. Indeed, PanIN-related adenocarcinoma showed more aggressive features and lower survival rate. Preneoplastic lesions may represent predictive factors for survival. Their role and predictive value should be investigated more thoroughly.

Biópsia percutânea por agulha grossa de tumores de partes moles guiada por tomografia computadorizada: resultados e correlação com análise da peça cirúrgica

OBJETIVO: Avaliar a eficácia da biópsia percutânea por agulha grossa (BPAG) de tumores de partes moles guiada por tomografia computadorizada (TC), em relação ao sucesso na obtenção de amostra para análise, e comparar o diagnóstico da BPAG com o resultado anatomopatológico da peça cirúrgica, quando disponível. MATERIAIS E MÉTODOS: Foram revisados os prontuários e laudos diagnósticos de 262 pacientes com tumores de partes moles submetidos a BPAG guiada por TC em um centro de referência oncológico entre 2003 e 2009. RESULTADOS: Das 262 biópsias realizadas, foi possível a obtenção de amostra adequada em 215 (82,1%). Os tumores mais prevalentes foram os sarcomas (38,6%), carcinomas metastáticos (28,8%), tumores mesenquimais benignos (20,5%) e linfomas (9,3%). Foi possível realizar graduação histológica em 92,8% dos pacientes com sarcoma, sendo a maioria (77,9%) classificada como alto grau. Do total de pacientes, 116 (44,3%) realizaram cirurgia para exérese e confirmação diagnóstica. A BPAG mostrou acurácia de 94,6% na identificação de sarcomas, com sensibilidade de 96,4% e especificidade de 89,5%. A graduação histológica teve concordância significativa entre a BPAG e a peça cirúrgica (p < 0,001; kappa = 0,75). CONCLUSÃO: A BPAG guiada por TC demonstrou elevada acurácia diagnóstica na avaliação de tumores de partes moles e na graduação histológica dos sarcomas, permitindo um adequado planejamento terapêutico.

Aplicação de um protocolo de espectroscopia por ressonância magnética das adrenais: experiência com mais de 100 casos

Objetivo: Avaliar um protocolo de espectroscopia por ressonância magnética (ERM) do próton de hidrogênio (1H) bidimensional (2D) disponível comercialmente (Siemens Medical Systems; Erlangen, Alemanha), aplicado para nódulos adrenais e diferenciação das massas (adenomas, feocromocitomas, carcinomas e metástases). Materiais e Métodos: Um total de 118 pacientes (36 homens e 82 mulheres), apresentando-se com 138 nódulos/massas adrenais, foi avaliado prospectivamente (média de idade: 57,3 ± 13,3 anos). Uma sequência de ERM-1H-PRESS-CSI (espectroscopia por resolução de ponto-imagem por desvio químico) multivoxel foi utilizada. Análise espectroscópica foi realizada da esquerda-direita, sentido crânio-caudal, usando três sequências sagitais, além de sequências axiais e coronais T2-HASTE. Os seguintes índices foram calculados: colina (Cho)/creatina (Cr), 4,0–4,3 ppm/Cr, lipídio (Lip)/Cr, Cho/Lip e lactato (Lac)/Cr. Resultados: ERM-1H-2D foi bem sucedida em 123 (89,13%) lesões. Os valores de sensibilidade e especificidade encontrados para as proporções e pontos de corte avaliados foram: Cho/Cr ≥ 1,2, sensibilidade de 100% e especificidade de 98,2% (diferenciação de adenomas e carcinomas de feocromocitomas e metástases); 4,0–4,3 ppm/Cr ≥ 1,5, 92,3% de sensibilidade, especificidade de 96,9% (diferenciação de carcinomas e feocromocitomas de adenomas e metástases); Lac/Cr ≤ –7,449, sensibilidade de 90,9% e especificidade de 77,8% (diferenciação de feocromocitomas contra carcinomas e adenomas). Conclusão: Os dados da ERM-1H-2D foram eficazes e permitiram a diferenciação entre massas adrenais e nódulos na maioria das lesões com diâmetro > 1,0 cm.

The role of gadoxetic acid as a paramagnetic contrast medium in the characterization and detection of focal liver lesions: a review

Recent studies have demonstrated that the use of paramagnetic hepatobiliary contrast agents in the acquisition of magnetic resonance images remarkably improves the detection and differentiation of focal liver lesions, as compared with extracellular contrast agents. Paramagnetic hepatobiliary contrast agents initially show the perfusion of the lesions, as do extracellular agents, but delayed contrast-enhanced images can demonstrate contrast uptake by functional hepatocytes, providing further information for a better characterization of the lesions. Additionally, this intrinsic characteristic increases the accuracy in the detection of hepatocellular carcinomas and metastases, particularly the small-sized ones. Recently, a hepatobiliary contrast agent called gadolinium ethoxybenzyl dimeglumine, that is simply known as gadoxetic acid, was approved by the National Health Surveillance Agency for use in humans. The authors present a literature review and a practical approach of magnetic resonance imaging utilizing gadoxetic acid as contrast agent, based on patients' images acquired during their initial experiment.

Hyperechoic breast lesions: anatomopathological correlation and differential sonographic diagnosis

Abstract Hyperechoic lesions are not a frequent finding at breasts ultrasonography, and most of times are associated with benign pathologies that do not require further evaluation. However, some neoplasms such as invasive breast carcinomas and metastases may present with hyperechogenicity. Thus, the knowledge about differential diagnoses and identification of signs of lesion aggressiveness are of great relevance to avoid unnecessary procedures or underdiagnosis, and to support the correct clinical/surgical approach. On the basis of such concepts, the present essay describes and illustrates the main features of hyperechoic lesions at breast ultrasonography in different cases, with anatomopathological correlation.

Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides

Green tea catechin inhibits fatty acid synthase without stimulating carnitine Palmitoyltransferase-1 or inducing weight loss in experimental animals

Background: The enzyme fatty acid synthase (FASN) is highly expressed in many human carcinomas and its inhibition is cytotoxic to human cancer cells. The use of FASN inhibitors has been limited until now by anorexia and weight loss, which is associated with the stimulation of fatty acid oxidation. Materials and Methods: The in vitro effect of (-)-epigallocatechin-3-gallate (EGCG) on fatty acid metabolism enzymes, on apoptosis and on cell signalling was evaluated. In vivo, the effect of EGCG on animal body weight was addressed. Results: EGCG inhibited FASN activity, induced apoptosis and caused a marked decrease of human epidermal growth factor receptor 2 (HER2), phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular (signal)-regulated kinase (ERK) 1/2 proteins, in breast cancer cells. EGCG did not induce a stimulatory effect on CPT-1 activity in vitro (84% of control), or on animal body weight in vivo (99% of control). Conclusion: EGCG is a FASN inhibitor with anticancer activity which does not exhibit cross-activation of fatty acid oxidation and does not induce weight loss, suggesting its potential use as an anticancer drug.

Targeted ablation of gonadotropin dependent endocrine tumors in transgenic mice through their luteinizing hormone receptor (LHR)

Gonadal somatic cell and adrenocortical endocrine tumors are rare. The incidence of adrenocortical carcinomas is only 1-2/1000000 a year. However, they are aggressive, especially in adulthood and currently surgery is the only curative treatment. Cytotoxic agents are in use in advanced cancers, but side effects and multidrug resistance are often problems. Thus there is a need for novel curative treatment methods. In contrast, ovarian granulosa cell tumors and testicular Leydig cell tumors are usually benign, especially at a younger age. The aim of the present thesis was to study a novel targeted treatment method through luteinizing hormone/chorionic gonadotropin receptor (LHCGR) in a transgenic mouse tumor model. The cytotoxic agent was lytic peptide Hecate-CGbeta conjugate where 23 amino acid Hecate, a synthetic form of honeybee venom melittin, was conjugated to 15 amino acid fragment of human chorionic gonadotropin β subunit. Lytic peptides are known to act only on negatively charged cells, such as bacteria and cancer cells and hereby, due to hCGbeta fragment, the conjugate is able to bind directly to LHCGR bearing cancer cells, saving the healthy ones. The experiments were carried out in inhibin-alpha-Simian Virus 40-T-antigen transgenic mice that are known to express LHCGR-bearing gonadal tumors, namely Leydig and granulosa cell tumors by 100% penetrance. If the mice are gonadectomized prepubertally they form adrenocortical tumors instead. Transgenic and wild type mice were treated for three consecutive weeks with control vehicle, Hecate or Hecate-CGbeta conjugate. GnRH antagonist or estradiol was given to a group of mice with or without Hecate-CGbeta conjugate to analyze the additive role of gonadotropin blockage in adrenocortical tumor treatment efficacy. Hecate-CGbeta conjugate was able to diminish the gonadal and adrenal tumor size effectively in males. No treatment related side effects were found. Gonadotropin blockage through GnRH antagonist was the best treatment in female adrenal tumors. The mode of cell death by Hecate-CGbeta conjugate was proven to be through necrosis. LHCGR and GATA-4 were co-expressed in tumors, where the treatment down-regulated their expression simultaneously, suggesting their possible use as tumor markers. In conclusion, the present thesis showed that Hecate-CGbeta conjugate targets its action selectively through LHCGR and selectively kills the LHCGR bearing tumor cells. It works both in gonadal somatic and in ectopic LHCGR bearing adrenal tumors. These results establish a more general principle that receptors expressed ectopically in malignant cells can be exploited in targeted cytotoxic therapies without affecting the normal healthy cells.

Novos produtos naturais capazes de atuar na estabilização de microtúbulos, um importante alvo no combate ao câncer

Microtubules are involved in many aspects of cellular biology and represent an important target of anticancer chemotherapeutics. In the past five years, novel natural products such as epothilones, discodermolide, sarcodictyin, eleutherobin, and laulimalide, all of which have biological activities similar to those of paclitaxel (Taxolâ), have been discovered. Taxolâ is an important antitumor drug approved by the FDA for the treatment of ovarian, breast and non-small-cell lung carcinomas and became the first natural product described that stabilized microtubules avoiding the cellular replication. The present article reports new natural products that are able to act on the stabilization of microtubules.

Osteonecrosis de maxilares asociada al uso de bifosfonatos: revisión de 491 casos

En los últimos años, el número de pacientes que presenta osteonecrosis maxilar asociada al uso de bifosfonatos (BIONJ) se ha incrementado. Esto es debido al aumento en el consumo de bifosfonatos, los cuales se asocian al tratamiento de carcinomas con metástasis óseas, mieloma múltiple, osteoporosis, osteopenia y enfermedades metabólicas como la enfermedad de Paget. Objetivo: Analizar el número de casos de pacientes que han desarrollado osteonecrosis de maxilares asociado al uso de bifosfonatos, publicados desde Junio del año 2006 hasta Abril 2010. Método: En esta revisión, se consultaron las bases de datos Pubmed-Medline, Scielo e Índice Médico Español, incluyendo límites en la búsqueda, para recopilar los casos de BIONJ que se hayan publicado desde el año 2006 hasta la actualidad. Los artículos seleccionados presentaban casos, en los cuales los pacientes que recibían bifosfonatos desarrollaban BIONJ. Resultados: Se encontraron 491 casos de BIONJ en total, de ellos 49,3% eran mujeres, 32% hombres y 18,7% no se establecía el género. La mayoría de estos casos se presentaron en la mandíbula y asociados particularment al ácido zolendrónico. Conclusiones: En los próximos años se espera que el número de pacientes que desarrollen esta complicación vaya en aumento, en particular en mujeres, a las cuales se les indica cada vez más esta medicación para el tratamiento de la osteoporosis.

The Cellular Oxygen Sensor PHD2 in Cancer Growth

Adequate supply of oxygen is essential for the survival of multicellular organisms. However, in several conditions the supply of oxygen can be disturbed and the tissue oxygenation is compromised. This condition is termed hypoxia. Oxygen homeostasis is maintained by the regulation of both the use and delivery of oxygen through complex, sensitive and cell-type specific transcriptional responses to hypoxia. This is mainly achieved by one master regulator, a transcription factor called hypoxiainducible factor 1 (HIF-1). The amount of HIF-1 is under tight oxygen-dependent control by a family of oxygen-dependent prolyl hydroxylase domain proteins (PHDs) that function as the cellular oxygen sensors. Three family members (PHD1-3) are known to regulate HIF of which the PHD2 isoform is thought to be the main regulator of HIF-1. The supply of oxygen can be disturbed in pathophysiological conditions, such as ischemic disorders and cancer. Cancer cells in the hypoxic parts of the tumors exploit the ability of HIF-1 to turn on the mechanisms for their survival, resistance to treatment, and escape from the oxygen- and nutrient-deprived environment. In this study, the expression and regulation of PHD2 were studied in normal and cancerous tissues, and its significance in tumor growth. The results show that the expression of PHD2 is induced in hypoxic cells. It is overexpressed in head and neck squamous cell carcinomas and colon adenocarcinomas. Although PHD2 normally resides in the cytoplasm, nuclear translocation of PHD2 was also seen in a subset of tumor cells. Together with the overexpression, the nuclear localization correlated with the aggressiveness of the tumors. The nuclear localization of PHD2 caused an increase in the anchorage-independent growth of cancer cells. This study provides information on the role of PHD2, the main regulator of HIF expression, in cancer progression. This knowledge may prove to be valuable in targeting the HIF pathway in cancer treatment.

Exposição e proteção solar dos estudantes de medicina de Curitiba (PR)

Trata-se de estudo observacional de corte transversal que teve como objetivo analisar a exposição e proteção solar de estudantes de Medicina de Curitiba (PR), através de questionário autoaplicado, comparando os resultados entre alunos de ambos os sexos que tiveram ou não intervenção da disciplina de Dermatologia. Análise estatística pelo Teste Exato de Fisher e Qui-Quadrado. Amostra composta de 398 estudantes com perfil sociodemográfico caracterizado principalmente por mulheres (54,9%), brancas, predominando a média de 23,8 anos. A maioria cursou a disciplina de Dermatologia (72,1%) e possui conhecimentos básicos sobre fotoproteção (65,3%). Quanto às práticas de exposição solar, os horários preferidos foram após 16 horas (55%) e entre 10-16 horas (23,3%), com uso diário de protetor solar (36,5%) e fator de proteção 30 ou superior (65,5%). Em relação aos riscos individuais para carcinomas cutâneos, 61,2% se enquadraram nos fototipos II e III de Fitzpatrick. Histórico familiar de câncer de pele ocorreu em 24,6% nos avós e/ou pais. Entre as mulheres que cursaram a disciplina de Dermatologia, verificou-se aplicação diária de fotoprotetor mais vezes ao dia e com fator de proteção solar mais alto.