Role of BI-RADS Ultrasound Subcategories 4A to 4C in Predicting Breast Cancer.

BACKGROUND: The Breast Imaging Reporting and Data System (BI-RADS) ultrasound (US) categorization revised in 2013 by the American College of Radiology resulted in unquestionable standardization of reports and confirmed category 3 and 5 as benign and malignant lesions, respectively. In contrast, suspected images (category 4) have subcategorization criteria, although theses have been detailed difficult to apply. The aim of the present study was to determine the role of the US 4A to 4C BI-RADS subcategories in predicting malignancy. PATIENTS AND METHODS: We performed a cross-sectional study of diagnostic tests to estimate the performance of the US BI-RADS categorization to clearly differentiate benign from malignant lesions. A total of 975 US examinations performed at the Hospital Femina, Grupo Hospitalar Conceição teaching hospitals from January 2012 through March 2015 were included in the present study. The US BI-RADS lexicon was used to classify the examination findings. Suspicious lesions underwent core needle biopsy, and the US and histology reports were compared to determine the performance using receiver operating characteristic curves. RESULTS: Overall, the BI-RADS US categorization showed good discriminating accuracy with a receiver operating characteristic curve of 91% (95% confidence interval [CI], 88%-93%). However, BI-RADS subcategory 4b had a positive predictive value of 25% (95% CI, 20%-31%) and subcategory 4A had a positive predictive value of only 6% (95% CI, 3.5%-9.8%). CONCLUSION: Our results have shown that US BI-RADS subcategories 4A and 4B are clearly unfit for use in screening tests, because they cannot rule out the need for biopsy. Therefore, management will not be improved by subcategorizing category 4, because all suspicious lesions will still require definite biopsy.

Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients.

STUDY OBJECTIVES: To characterize the steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients requiring seizure prophylaxis after a neurologic injury and to determine which dosing regimens achieve serum concentrations within the recommended therapeutic range of 6-20 µg/ml. DESIGN. Prospective, open-label, steady-state pharmacokinetic study. SETTING: Neurocritical care unit in a tertiary care medical center. PATIENTS. Twelve adults (five men, seven women) admitted to the neurocritical care unit who required prophylactic anticonvulsant therapy after subarachnoid hemorrhage, subdural hematoma, or traumatic brain injury. INTERVENTION: Patients received an intravenous infusion of levetiracetam 500 mg over 15 minutes every 12 hours. MEASUREMENTS AND MAIN RESULTS: Serial blood samples were collected from all patients after a minimum of four doses of therapy. Serum levetiracetam concentrations were determined by ultraperformance liquid chromatography with tandem mass spectrometry detection, and pharmacokinetic data were analyzed by compartmental and noncompartmental methods. Monte Carlo simulations were performed for multiple levetiracetam dosing regimens to determine the probability of achieving a target trough concentration of 6 µg/ml or greater, 20 µg/ml or greater, and 6-20 µg/ml. The mean ± SD levetiracetam maximum serum concentration was 28.0 ± 8.0 µg/ml, minimum serum concentration 3.1 ± 1.8 µg/ml, half-life 5.2 ± 1.2 hours, systemic clearance 5.6 ± 1.8 L/hour, and volume of distribution at steady state 36.8 ± 6.3 L. Increasing the doses of levetiracetam increased the probability of achieving a target trough concentration of 6 µg/ml or greater but also increased the probability of achieving trough concentrations greater than 20 µg/ml. Levetiracetam doses of 1000 mg every 8 hours and 1500-2000 mg every 12 hours provided the highest probability of achieving a target trough concentration between 6 and 20 µg/ml. CONCLUSION: Compared with previously published results in healthy volunteers and adults in status epilepticus, levetiracetam systemic clearance was faster and the terminal elimination half-life was shorter in neurocritical care patients. Higher doses or more frequent dosing may be needed to achieve target trough concentrations of 6-20 µg/ml.

Pituitary macroadenoma in a patient with POEMS syndrome in conjunction with Castleman disease: first report of a case and review of related literature.

OBJECTIVE: To describe the first reported case of a patient with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) in conjunction with the endocrinologic manifestation of panhypopituitarism due to a large clinically nonfunctioning pituitary adenoma. METHODS: We present the clinical, laboratory, and radiologic details of the case and review the relevant updated literature. RESULTS: A 48-year-old man with hypopituitarism and progressive polyneuropathy presented to an outside hospital with confusion and diaphoresis. He also had diffuse lymphadenopathy, monoclonal gammopathy, and skin lesions consistent with a diagnosis of POEMS syndrome. Cytopathologic study of a lymph node showed findings consistent with Castleman disease. A large suprasellar mass was found to be the cause of the hypopituitarism. CONCLUSION: POEMS syndrome is a rare paraneoplastic condition, commonly associated with Castleman disease, that manifests with progressive distal polyneuropathy and a monoclonal plasma cell disorder, often accompanied by endocrinopathy, organomegaly, skin changes, sclerotic bone lesions, ascites, erythrocytosis, and thrombocytosis. Our current patient had all 5 classic features of POEMS syndrome along with some diagnostic elements of Castleman disease, sclerotic bone lesions, and thrombocytosis. To our knowledge, this is the first known reported case of a patient whose endocrinologic manifestation of POEMS syndrome was panhypopituitarism attributable to a large clinically nonfunctioning pituitary adenoma.

[Reversal of digital clubbing in surgically treated lung cancer patients]. / Regressão do hipocratismo digital em pacientes com câncer de pulmão tratados cirurgicamente.

OBJECTIVE: To objectively evaluate the reversal of digital clubbing (DC) in a series of surgically treated lung cancer patients, and to review the literature on the subject. METHODS: Sixty-one patients with non-small cell lung cancer--40 with and 21 without DC--were treated by pulmonary resection. Eleven (18%) received additional postoperative radiation therapy. Preoperatively, as well as on postoperative days 7, 18, and 90, the hyponychial angle (HA) and the distal phalangeal depth/interphalangeal depth (DPD/IPD) ratio were determined on profile shadow projections of the index fingers. A review of the literature on reversal of DC (1954-2007) was also performed. RESULTS: From the preoperative period to postoperative day 90, HA decreased from 200.5 +/- 5.0 masculine to 193.3 +/- 6.8 masculine (p < 0.001), and the DPD/IPD ratio decreased from 1.014 +/- 0.051 mm to 0.956 +/- 0.045 mm (p < 0.001) in the group of 40 patients with DC. The HA and the DPD/IPD ratio decreased in 33 (82.5%) but remained the same in 7 (1.7%), 6 with unfavorable evolution. In the 21 patients without DC, HA (184.5 +/- 5.5 masculine) and the DPD/IPD ratio (0.937 +/- 0.046 mm) remained unchanged after surgery. In the literature (1954-2007), we found 52 cases, 5 of which were lung cancer cases, in which reversal of DC, observed in several clinical conditions, was explicitly reported. CONCLUSION: In most lung cancer patients, DC resolves after effective surgical treatment of the tumor, as can occur in patients with other conditions.

Regressão do hipocratismo digital em pacientes com câncer de pulmão tratados cirurgicamente / Reversal of digital clubbing in surgically treated lung cancer patients

OBJETIVO: Estudar, por meio de avaliações objetivas, a ocorrência de regressão do hipocratismo digital (HD) em pacientes com câncer de pulmão, tratados cirurgicamente, e revisar a literatura sobre o assunto. MÉTODOS: Sessenta e um pacientes com câncer de pulmão não-pequenas células-40 com e 21 sem HD-foram tratados por cirurgia de ressecção pulmonar. Onze deles (18 por cento) também receberam radioterapia pós-operatória. No período pré-operatório e no 7º, no 18º e no 90º dia pós-operatório, o ângulo hiponiquial (AH) e a relação entre as espessuras falangeana distal e interfalangeana (EFD/EIF) foram determinados sobre imagens da sombra dos dedos indicadores em perfil. Uma revisão da literatura sobre regressão do HD (1954-2007) também foi efetuada. RESULTADOS: Do período pré-operatório ao 90º dia pós-operatório, o AH diminuiu de 200,5 ± 5,0º para 193,3 ± 6,8º (p < 0,001), e a relação EFD/EIF, de 1,014 ± 0,051 mm para 0,956 ± 0,045 mm (p < 0,001) no grupo de 40 pacientes com HD. Em 33 (82,5 por cento), o AH e a relação EFD/EIF diminuíram, mas, em 7 (1,7 por cento), 6 com evolução desfavorável, esses valores não se reduziram. Nos 21 pacientes sem HD, tanto o AH (184,5 ± 5,5º) como a relação EFD/EIF (0,937 ± 0,046 mm) permaneceram inalterados após a cirurgia. Na literatura (1954-2007) foram encontrados 52 casos em que a regressão do HD, observada em diversas condições clínicas, foi explicitamente referida, 5 dos quais eram casos de câncer de pulmão. CONCLUSÕES: O HD em pacientes com câncer de pulmão regride na maioria dos casos após tratamento cirúrgico efetivo do tumor, o que pode também ocorrer em pacientes com outras condições.

OBJECTIVE: To objectively evaluate the reversal of digital clubbing (DC) in a series of surgically treated lung cancer patients, and to review the literature on the subject. METHODS: Sixty-one patients with non-small cell lung cancer-40 with and 21 without DC-were treated by pulmonary resection. Eleven (18 percent) received additional postoperative radiation therapy. Preoperatively, as well as on postoperative days 7, 18, and 90, the hyponychial angle (HA) and the distal phalangeal depth/interphalangeal depth (DPD/IPD) ratio were determined on profile shadow projections of the index fingers. A review of the literature on reversal of DC (1954-2007) was also performed. RESULTS: From the preoperative period to postoperative day 90, HA decreased from 200.5 ± 5.0º to 193.3 ± 6.8º (p < 0.001), and the DPD/IPD ratio decreased from 1.014 ± 0.051 mm to 0.956 ± 0.045 mm (p < 0.001) in the group of 40 patients with DC. The HA and the DPD/IPD ratio decreased in 33 (82.5 percent) but remained the same in 7 (1.7 percent), 6 with unfavorable evolution. In the 21 patients without DC, HA (184.5 ± 5.5º) and the DPD/IPD ratio (0.937 ± 0.046 mm) remained unchanged after surgery. In the literature (1954-2007), we found 52 cases, 5 of which were lung cancer cases, in which reversal of DC, observed in several clinical conditions, was explicitly reported. CONCLUSION: In most lung cancer patients, DC resolves after effective surgical treatment of the tumor, as can occur in patients with other conditions.

P53 and BCL-2 as prognostic markers in endometrial carcinoma.

The objective of this study was to verify the frequency of p53 and BCL-2 immunohistochemical expression in patients with endometrial carcinoma and to correlate it with histological factors (histological type, tumor grade, depth of myometrial invasion, lymph node involvement and surgical staging) and survival. Forty-eight patients with endometrial carcinoma who were submitted to primary surgical treatment were assessed. p53 and BCL-2 immunohistochemical expression was determined using paraffin blocks containing the tumor area. p53 and BCL-2 expression was detected in 39.6% and 58.3% of the tumors, respectively. No significant difference was found regarding the frequency of p53 expression when analyzing histological type (33.3% in endometrioid tumors, 58.3% in non-endometrioid tumors; p = 0.176), depth of myometrial invasion (p = 0.632) and surgical staging (I-11.1%, II-66.7%, III-57.1%; p = 0.061). p53 expression was significantly more frequent in undifferentiated tumors (p = 0.007) and in those showing lymph node involvement (p = 0.030). Univariate analysis showed a positive association with death (RR, 3.358; CI, 1.386-8.134; p = 0.005) and short-term survival. The present study did not reveal any correlation between BCL-2 expression and histopathologic markers or survival. In conclusion, this study showed that p53 expression is directly correlated with undifferentiated tumors, lymph-node involvement and risk of death. On the other hand, BCL-2 expression was not correlated with any known histological factors.

Aplicação do índice prognóstico de Nottingham em pacientes com câncer de mama atendidas em um hospital público / Application of the Nottingham prognosis index in breast cancer patients treated at a public hospital

Um estudo de coorte histórico foi desenvolvido incluindo 116 pacientes com câncer de mamaatendidas no Hospital Femina, Grupo Hospitalar Conceição (GHC), Ministério da Saúde (MS),entre setembro de 1997 e dezembro de 2000. Foi aplicado o índice prognóstico de Nottingham(IPN) na população em estudo e avaliada a sua associação com a recidiva da doença. O IPNconseguiu identificar um grupo com bom prognóstico, em que de 26 pacientes somente 2 (7,7%)evoluíram para recidiva, e um grupo de 32 pacientes com pobre prognóstico, em que 24 delas(75%) evoluíram para recidiva em cinco anos. Nesta amostra composta de pacientes provenientesda rede pública, a média e o desvio-padrão do tamanho tumoral foi de 3,1 ± 1,8 cm e somente25% das mulheres apresentaram tumores menores do que 2 cm na primeira consulta no hospitalterciário. Isso sugere que o diagnóstico de câncer de mama ainda está sendo realizado tardiamente,em nosso meio.

A history cohort study that included 116 breast cancer patients treated at the Femina Hospital, GrupoHospitalar Conceição (GHC), Health Ministry (HM), between September 1997 to December 2000 wasconducted. The Nottingham Prognostic Index (NPI) and its association with the disease recidivationwas assessed in the study population. The NPI identified two groups; good prognosis group (n = 26) with7.7% recidivation and a poor prognosis group (n = 32) with 75% recidivation at 5 years. The tumorsize in our study population was 3.1 ± 1.8 cm and it was less than 2 cm in only 25% of the patients atthe first consultation at a tertiary hospital. These observations suggested that the breast cancer diagnosis isperformed late in our environment.

Pulmonary epithelial permeability in patients treated with bleomycin containing chemotherapy detected by technetium-99m diethylene triamine penta-acetic acid aerosol (99mTc-DTPA) scintigraphy.

PURPOSE: To evaluate pulmonary epithelial permeability using 99mTc-DTPA scintigraphy in patients treated with bleomycin-containing regimens. MATERIAL AND METHODS: Twelve non-smoking chemotherapy-naïve patients with no clinical or radiological evidence of pulmonary disease and treated with bleomycin-containing chemotherapy were tested with 99mTc-DTPA scintigraphy before the first cycle and every 3 weeks until the third month after the end of chemotherapy (total cumulative dose of bleomycin 347.9 mg). RESULTS: Pretreatment values (T1/2 74.93 minutes) of 99mTc-DTPA scintigraphy were significantly higher than those obtained after the total dose of bleomycin (T1/2 51.00 minutes) (p < 0.001). This difference was more important in the later evaluations especially, on the third week and third month measures after discontinuing treatment (p < 0.001). All the tests of Within-Subjects Effects were significant (p < 0.001). Comparing pretreatment and post-treatment scintigraphies the mean T1/2 99mTc-DTPA values decreased as the bleomycin dose increased. CONCLUSION: We conclude that cumulative bleomycin doses are related to increased pulmonary epithelial permeability at a dose of 256.5 mg. However, whether this is related to clinical toxicity is uncertain and large, multi-center prospective studies are needed.

Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial.

BACKGROUND: the study was designed to test whether vitamin E (VE) provides oral mucosal protection in patients with irradiated cancers of the head and neck. METHODS: Fifty-four patients with cancer of the oral cavity and oropharynx were randomly assigned to rinse the oral cavity in an oil solution containing either VE or placebo before every conventional fraction of 2 Gy and again 8 to 12 hours later during the 5 to 7 weeks of radiotherapy (RT). RESULTS: Thirty-six events/167 patient-weeks (21.6%) and 54 events/161 patient-weeks (33.5%) of symptomatic mucositis were observed in VE and placebo groups, respectively (p =.038). VE reduced the risk by 36%. Subjective data at the end of the treatment revealed that VE decreased pain grades 2 to 3 during RT (3 of 28 patients vs 14 of 26 patients, p =.0001). No significant influence was detected in survival. CONCLUSION: VE decreased the incidence of symptomatic oral radio-induced mucositis in patients with cancer of the oropharynx and oral cavity.

Prognostic factors in irradiated patients with locally advanced non-small cell lung cancer (NSCLC)

Over the last 20 years the prognostic factors in NSCLhave been studies predominantly in surgical series. Their importance in clinically staged patients submitted to radiation therapy (RT) alone have not been sufficiently substantiated. We analyzed clinicoanatomical factors in 43 prospectively studied patients with inoperable tumors treated with definitive irradiation (60 GY/6 weeks). The only significant factors were the chest ivasion and response to RT. The median survivals for patients with and without chest wall invasion were 5.5 and 11.0 months, respectively (p=0.04), with corresponding 1 and 2-years survival rates of 33 and 0 percent, and 54 and 16 percent, respectively. Measurable responses were partial in 24 (55.8 percent) and complete in 7 patients (16.3 percent). The median survivals for responders and nonresponders were 13.0 and 5.0 months, respectively, with 2-year survival of 21 percent and 0 percent, respectively (p=0.00001). The local control rate was 11.6 percent respectively. These data suggest that irradiation is not an useful treatment for patients with chest wall invasion, and that responders have longer survival.

Respiratory disease in neutropenic patients: diagnosis and treatment

The associations between malignancy, immunossupression and infectious morbidity and mortality have been established, and the use of more intensive chemotherapic regimens have produced a higher number of immunosuppressed oncologic patients. Thus, the benefits of the antineoplastic therapy can be limited by the mortality associated with the complications of life-threatening infection. This have raised the necessity of empiric therapy, which main goal is to prevent the death in the carly stage, until a more specific choice can be determined based on the results of the bacteriological examination and the patient's response. Pulmonary infiltrates, which are generally the first manifestation of respiratory infection in immunocompromised patients, can be classified as localized (early, refractory or late) or diffuse. this classification helps to establish more directed empiric approaches. The choices of the initial empiric antibiotic therapy include (a) aminoglycoside + extended-spectrum beta-lactam, (b) complication of 2 beta-lactams, or (c) extended-spectrum monotherapy. It is also possible to coadministrate speciffically oriented. The optimal duration of empiric therapy and empiric antifungal therapy are also discussed in this review. The prevention of pulmonary infections is justified by the reduction in the morbidity, mortality, and hospital costs. Selective decontamination with the use of agents that preserve the anaerobic flora have had variable results, being SMZ/TMP the agent more commonly used for this purpose. Hemotopoietic growth factors have shown to be effective in reducing the duration and the severity, but not the incidence of the chemotherapy-associated neutropenia, the number of infection episodes, or the mortally associated to infection.

Marcadores tumorais / Tumor markers

Os autores apresentam os marcadores tumorais mais utilizados na pratica da clinica, associando-os ao diagnostico e seguimento de doencas malignas

Growth factors and differentiation - a new concept in the evaluation of germ cell tumor biological behavior

Fatores de crescimento e oncogenes tem sido recentemente associados a alteraçöes biológicas relacionadas a transformaçäo neoplásica. Hipóteses sugerindo um modelo autócrino tem sido propostas por vários autores. Os fatores de crescimento aparecem estar também relacionados com a regulaçäo da embriogenese precoce. Estudos recentes tem indicado que as células de carcinoma embrionário se assemelham bastante aos grupos celulares internos do embriäo precoce normal. Essa estreita relaçäo entre célula embrionárias normais e células de teratocarcinoma sugere uma funçäo reguladora similar dos fatores de crescimento com ambos os casos

Tumor de Wilms / Wilms' tumor

Säo relatados 4 casos de pacientes tratados no Hospital de Clínicas por tumor de Wilms que apesar de apresentarem grandes volumes, foi realizada a cirurgia primariamente com posterior radioterapia e quimioterapia

Carcinoma brônquico avenocelular em portadora de handeníase com dapsona / Bronchogenic carcinoma oat cell in carriers of hanseniasis treated with Dapsona

Os autores relatam o caso de uma paciente de 49 anos, tabagista, portadora de carcinoma brônquico avenocelular e hanseniase, em uso de dapsona há 4 anos. Procuram estabelecer as possíveis correlaçöes entre o carcinoma brônquico avenocelular, a hanseníase e a falência da imunidade celular, acrescidas do eventual efeito carcinogênico da dapsona