Combined Visual and Semiquantitative Evaluation Improves Outcome Prediction by Early Midtreatment 18F-FDG PET in Diffuse Large B-Cell Lymphoma.

The purpose of this study was to assess the predictive and prognostic value of interim FDG PET (iPET) in evaluating early response to immunochemotherapy after 2 cycles (PET-2) in diffuse large B-cell lymphoma (DLBCL) by applying 2 different methods of interpretation: the Deauville visual 5-point scale (5-PS) and a change in SUV (ΔSUV) by semiquantitative evaluation. Methods: In total, 145 patients with newly diagnosed DLBCL underwent pretreatment PET and PET-2 assessment. PET-2 was classified according to both 5-PS and percentage ΔSUV. Receiver-operating-characteristic analysis was performed to compare the accuracy of the 2 methods for predicting progression-free survival. Survival estimates, based on each method separately and combined, were calculated for iPET-positive (iPET+) and iPET-negative (iPET-) groups and compared. Results: Both with 5-PS and with ΔSUV-based evaluations, significant differences were found between the progression-free survival of iPET- and iPET+ patient groups (P < 0.001). Visually, the best negative predictive value (NPV) and positive predictive value (PPV) occurred when iPET was defined as positive if the Deauville score was 4-5 (89% and 59%, respectively). Using the 66% ΔSUV cutoff reported previously, NPV and PPV were 80% and 76%, respectively. ΔSUV at the 48.9% cutoff, reported for the first time here, produced 100% specificity along with the highest sensitivity (24%). The 5-PS and a semiquantitative ΔSUV of less than 48.9% for each PET-2 gave the same PET-2 classification (positive or negative) in 70% (102/145) of all patients. This combined classification delivered NPV and PPV of 89% and 100%, respectively, and all iPET+ patients failed to achieve or remain in remission. Conclusion: In this large consistently treated and assessed series of DLBCL patients, iPET had good prognostic value interpreted either visually or semiquantitatively. We determined that the most effective ΔSUV cutoff was 48.9% and that when combined with 5-PS assessment, a positive PET-2 result was highly predictive of treatment failure.

Shock-Wave Therapy Improves Myocardial Blood Flow Reserve in Patients with Refractory Angina: Evaluation by Real-Time Myocardial Perfusion Echocardiography.

BACKGROUND: Cardiac shock-wave therapy (CSWT) has been demonstrated as an option for the treatment of patients with refractory angina (RA), promoting immediate vasodilatory effects and, in the long-term, neoangiogenic effects that would be responsible for reducing the myocardial ischemic load. The aim of this study was to determine the effects of CSWT on myocardial blood flow reserve (MBFR) assessed by quantitative real-time myocardial perfusion echocardiography in patients with RA. METHODS: Fifteen patients (mean age 61.5 ± 12.8 years) with RA who underwent CSWT during nine sessions, over 3 months of treatment, were prospectively studied. A total of 32 myocardial segments with ischemia were treated, while another 31 did not receive therapy because of technical limitations. Myocardial perfusion was evaluated at rest and after dipyridamole stress (0.84 mg/kg) before and 6 months after CSWT, using quantitative real-time myocardial perfusion echocardiography. Clinical effects were evaluated using Canadian Cardiovascular Society grading of angina and the Seattle Angina Questionnaire. RESULTS: The ischemic segments treated with CSWT had increased MBFR (from 1.33 ± 0.22 to 1.74 ± 0.29, P < .001), a benefit that was not observed in untreated ischemic segments (1.51 ± 0.29 vs 1.54 ± 0.28, P = .47). Patients demonstrated increased global MBFR (from 1.78 ± 0.54 to 1.89 ± 0.49, P = .017). Semiquantitative single-photon emission computed tomographic analysis of the treated ischemic segments revealed a score reduction from 2.10 ± 0.87 to 1.68 ± 1.19 (P = .024). There was improvement in Canadian Cardiovascular Society score (from 3.20 ± 0.56 to 1.93 ± 0.70, P < .05) and in Seattle Angina Questionnaire score (from 42.3 ± 12.99 to 71.2 ± 14.29, P < .05). No major cardiovascular events were recorded during follow-up. CONCLUSIONS: CSWT improved MBFR in ischemic segments, as demonstrated by quantitative real-time myocardial perfusion echocardiography. These results suggest that CSWT has the potential to increase myocardial blood flow, with an impact on symptoms and quality of life in patients with RA.

Prospective international cohort study demonstrates inability of interim PET to predict treatment failure in diffuse large B-cell lymphoma.

UNLABELLED: The International Atomic Energy Agency sponsored a large, multinational, prospective study to further define PET for risk stratification of diffuse large B-cell lymphoma and to test the hypothesis that international biological diversity or diversity of healthcare systems may influence the kinetics of treatment response as assessed by interim PET (I-PET). METHODS: Cancer centers in Brazil, Chile, Hungary, India, Italy, the Philippines, South Korea, and Thailand followed a common protocol based on treatment with R-CHOP (cyclophosphamide, hydroxyadriamycin, vincristine, prednisolone with rituximab), with I-PET after 2-3 cycles of chemotherapy and at the end of chemotherapy scored visually. RESULTS: Two-year survivals for all 327 patients (median follow-up, 35 mo) were 79% (95% confidence interval [CI], 74%-83%) for event-free survival (EFS) and 86% (95% CI, 81%-89%) for overall survival (OS). Two hundred ten patients (64%) were I-PET-negative, and 117 (36%) were I-PET-positive. Two-year EFS was 90% (95% CI, 85%-93%) for I-PET-negative and 58% (95% CI, 48%-66%) for I-PET-positive, with a hazard ratio of 5.31 (95% CI, 3.29-8.56). Two-year OS was 93% (95% CI, 88%-96%) for I-PET-negative and 72% (95% CI, 63%-80%) for I-PET-positive, with a hazard ratio of 3.86 (95% CI, 2.12-7.03). On sequential monitoring, 192 of 312 (62%) patients had complete response at both I-PET and end-of-chemotherapy PET, with an EFS of 97% (95% CI, 92%-98%); 110 of these with favorable clinical indicators had an EFS of 98% (95% CI, 92%-100%). In contrast, the 107 I-PET-positive cases segregated into 2 groups: 58 (54%) achieved PET-negative complete remission at the end of chemotherapy (EFS, 86%; 95% CI, 73%-93%); 46% remained PET-positive (EFS, 35%; 95% CI, 22%-48%). Heterogeneity analysis found no significant difference between countries for outcomes stratified by I-PET. CONCLUSION: This large international cohort delivers 3 novel findings: treatment response assessed by I-PET is comparable across disparate healthcare systems, secondly a negative I-PET findings together with good clinical status identifies a group with an EFS of 98%, and thirdly a single I-PET scan does not differentiate chemoresistant lymphoma from complete response and cannot be used to guide risk-adapted therapy.

Echocardiographic and hemodynamic determinants of right coronary artery flow reserve and phasic flow pattern in advanced non-ischemic cardiomyopathy.

BACKGROUND: In patients with advanced non-ischemic cardiomyopathy (NIC), right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA) flow pattern and flow reserve (CFR) are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. METHODS: Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire) data was obtained in RCA and left anterior descendent coronary artery (LAD) before and after adenosine. Resting RCA phasic pattern (diastolic/systolic) was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV) dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress) more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. RESULTS: LV fractional shortening and end diastolic diameter were 15.3 +/- 3.5 % and 69.4 +/- 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS) either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS); RCA vs. LAD was 1.35 vs. 2.85 (p < 0.001). It had no significant correlation among any cardiac mechanical or hemodynamic parameter with RCA-CFR or RCA flow pattern. RCA-CFR had no difference compared with LAD (3.38 vs. 3.34, p = NS), as well as in pulmonary hypertension (3.09 vs. 3.10, p = NS) either in RV dysfunction (3.06 vs. 3.22, p = NS) subgroups. CONCLUSION: In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or hemodynamic parameter with RCA-CFR or RCA phasic flow pattern. RCA flow reserve is still similar to LAD, independently of those right-sided cardiac disturbances.

Uptake of a cholesterol-rich emulsion by breast cancer.

OBJECTIVE: Overexpression of low-density lipoprotein (LDL) receptors occurs in several cancer cell lines and offers a unique strategy for drug targeting by using LDL as vehicle. However, the native lipoprotein is difficult to obtain and handle. Previously, we showed that a lipidic emulsion (LDE) similar to the lipid structure of native LDL may bind to LDL receptors and be taken up by acute myelocytic leukemia cells. We also showed that LDE can also concentrate in ovarian cancer tissue. In this study, we tested whether LDE is taken up by breast carcinoma. METHODS: LDE labeled with (99m)Tc was injected into 18 breast cancer patients, and nuclear medicine images of the tumor and metastatic sites were acquired. Subsequently, LDE labeled with [3H]cholesteryl oleate was intravenously injected into 14 breast cancer patients 24-30 h before total mastectomy procedure. Fragments of normal and of breast cancer tissue excised during surgery were lipid extracted with chloroform/methanol and their radioactivity was measured in a scintillation solution. RESULTS: (99m)Tc-LDE images of the primary tumor and of metastasis sites were obtained in all 18 breast cancer patients. As directly measured in the tumor and in the normal mammary tissue, the amount of the emulsion radioactive label in the tumor was 4.5 times greater than in the normal tissue (range 1.2- to 8.8-fold). CONCLUSION: LDE concentrates much more in malignant breast tumor tissue than in the normal tissue. Thus it has potential to carry drugs or radionuclides directed against mammary carcinoma cells for diagnostic or therapeutic purposes.

Estudo diagnóstico de um caso de gagueira desenvolvimental com uso de PET (Positron Emission Tomography) / A case study of idiopathic stuttering using PET scan (Positron Emission Tomography)

Tema: diagnóstico de gagueira com uso de Positron Emission Tomography (PET). Objetivo: apresentar o perfil da fluência da fala e do PET em um caso de gagueira desenvolvimental. Material e Método: participou deste estudo um indivíduo de 20 anos, do sexo masculino, com gagueira, sem antecedência genética de primeiro grau. Para obtenção das imagens do PET foram realizadas duas avaliações: a primeira com o estímulo de fala e a segunda com o paciente em repouso. Resultados: o paciente avaliado apresentou todos os parâmetros da fluência de fala desviados do normal. Quanto ao PET, não foram identificadas correlações corticais específicas entre as duas condições de avaliação. Conclusão: os achados estão compatíveis com a literatura.

Efeito do carvedilol na insuficiência cardíaca por cardiomiopatia dilatada: resultado de estudo duplo-cego, randômico, com grupo placebo-controle (estudo CARIBE) / Effects of carvedilol in heart failure due to dilated cardiomyopathy: results of a double-blind randomized placebo-controlled study (CARIBE study)

OBJECTIVE: To assess the effects of carvedilol in patients with idiopathic dilated cardiomyopathy. METHODS: In a double-blind randomized placebo-controlled study, 30 patients (7 women) with functional class II and III heart failure were assessed. Their ages ranged from 28 to 66 years (mean of 43ñ9 years), and their left ventricular ejection fraction varied from 8 per cnet to 35 per cent. Carvedilol was added to the usual therapy of 20 patients; placebo was added to the usual therapy of 10 patients. The initial dose of carvedilol was 12.5 mg, which was increased weekly until it reached 75 mg/day, according to the patient's tolerance. Clinical assessment, electrocardiogram, echocardiogram, and radionuclide ventriculography were performed in the pretreatment phase, being repeated after 2 and 6 months of medication use. RESULTS: A reduction in heart rate (p=0.016) as well as an increase in left ventricular shortening fraction (p=0.02) and in left ventricular ejection fraction (p=0.017) occurred in the group using carvedilol as compared with that using placebo. CONCLUSION: Carvedilol added to the usual therapy for heart failure resulted in better heart function.

Magnetic Resonance Imaging in Chronic Chagas' Disease: Correlation with Endomyocardial Biopsy Findings and Gallium-67 Cardiac Uptake.

BACKGROUND: We studied the correlation among cardiac magnetic resonance imaging (MRI), gallium-67 myocardial uptake, and right ventricular endomyocardial biopsy results in chronic Chagas' disease. To our knowledge, this represents the first attempt to correlate the histological findings with cardiac MRI and gallium-67 myocardial uptake for noninvasive diagnosis of inflammatory activity associated with Chagas' disease. METHODS: Ten male patients with cardiomyopathy secondary to Chagas' disease were studied (mean age, 47.7 +/- 7 years; congestive heart failure New York Heart Association [NYHA] functional class II [two patients], III [six patients], and IV [two patients]; and mean echocardiographic left ventricular [LV] ejection fraction [EF], 36 +/- 6%). The patients underwent right ventricular endomyocardial biopsy, cardiac MRI, and gallium-67 myocardial uptake testing. The results of this group were compared with those of a control group of patients with idiopathic dilated cardiomyopathy who were matched in age (mean age, 46 +/- 10 years), LV function (mean echocardiographic EF, 30 +/- 4%), and NYHA classification (one patient in class II, five patients in class III, and one patient in class IV). RESULTS: All patients with Chagas' disease showed higher signal intensity on MRI after the administration of gadolinium. The intensity of the septal signal changed from 0.90 +/- 0.11 to 1.56 +/- 0.19 (P < 0.001). In the control group, there was no difference in signal intensity with gadolinium (mean septal intensity, 0.94 +/- 0.12 before and 0.99 +/- 0.15 after; NS). On biopsy, eight chagasic patients had evident signs of myocarditis, and two patients had borderline evidence myocarditis. However, only one patient in the control group had a histological diagnosis of borderline myocarditis. Gallium-67 cardiac uptake was positive for myocardial inflammatory process in seven chagasic patients and borderline in one. On the other hand, only one patient in the control group had an uptake that was positive for inflammation, and one had a borderline result. CONCLUSIONS: In conclusion, the data from this study strongly suggest that myocarditis is frequently found in Chagas' disease. Cardiac MRI appears to be an accurate and alternative method for the diagnosis of inflammatory process associated with Chagas' disease.

Evolução pós-operatória da função ventricular esquerda na insuficiência aórtica / Postoperative Left Ventricular Function Evolution in Aortic Insufficiency

PURPOSE--To analyze the follow-up of left ventricular function (LVF) after surgical correction of severe chronic aortic insufficiency (AI). METHODS--Twenty-one out of 68 patients with AI, initially asymptomatic and that developed symptoms during the follow-up period of 24-36 months, were studied. Relationship between symptoms and LVF by echocardiogram and radioisotopic ventriculography at rest and in isotonic exercise were studied. Three clinical moments (CM) were assumed: CM-0- at the beginning of the study, when all patients were asymptomatic; CM-1- manifestation of the symptoms during 24-36 months; CM-2- corresponding to the late post-operative period of 8 months of 20 out of 21 patients (one refused the surgery). The analysis did not show any significant differences between the mean values of all echocardiographic variables (diastolic and systolic diameters, shortening fraction, final systolic stress, volume-mass ratio, contractility index) and the ejection fraction of the left ventricle (EF) obtained by the radioisotope ventriculography at rest and, including exercise, between clinical moments 0 and 1. RESULTS--In the CM-2, involution was verified for functional class I/II in all cases and absence of expressive complications or immediate or late postoperative mortality. Comparison between CM-2 and 0 showed expressive regression of the diameters at rest in the postoperative period and with significant improvement in the means mainly the percentual variation of the EF and total time of effort. CONCLUSION--Symptoms assembled patients with more advanced eccentric hypertrophy and did not coincide with any immediate change in findings studied at rest and at exercise. It represented a point of reference for surgical indication compatible with late postoperative involution of chronic adaptation of AI.

Objetivo - Analisar a evolução da função ventricular esquerda (FVE) após correção cirúrgica da insuficiência aórtica crônica grave (IAo). Métodos - Dentre 68 portadores de IAo, inicialmente assintomáticos, selecionamos 21 que desenvolveram sintomas durante período de observação de 24-36 meses. Estudamos a FVE através do ecodopplercardiograma e da ventriculografia radioisotópica em repouso e em exercício isotônico em três momentos clínicos (MC): MC-0 - ao início do estudo e todos os pacientes eram assintomáticos; MC-1 - manifestação de sintomas no decorrer de 24-36 meses; MC-2 - período pós-operatório tardio de 8 meses de 20 dos 21 casos (houve uma recusa à cirurgia). Não havia diferenças significantes entre as médias de todas as variáveis ecocardiográficas estudadas (diâmetro diastólico, diâmetro sistólico, fração de encurtamento, estresse sistólico final, relação volume-massa, índice de contratilidade) e da fração de ejeção do ventrículo esquerdo (FE) obtida pela ventriculografia radioisotópica em repouso e, inclusive ao exercicio, entre os MC - 0 e 1. Resultados - No MC-2 constatou -se involução para classe funcional I/II em todos os casos e ausência de mortalidade pós-operatória imediata e tardia. Da comparação entre os MC - 2 e 0, houve expressiva regressão dos diâmetros em repouso no pós-operatório e com melhora significante entre as médias, principalmente da variação percentual da FE e do tempo total de esforço. Conclusão - A manifestação de sintomas reuniu pacientes com hipertrofia excêntrica avançada, não coincidiu com nenhuma mudança imediata dos marcadores laboratoriais estudados ao repouso e ao exercício, e representou ponto de referência de indicação cirúrgica compatível com involução pós-operatória tardia das conseqüências da adaptação IAo

Drogas imunossupressoras no tratamento da miocardite ativa na criança: avaliaçäo hemodinâmica / Imunosuppressive therapy in the treatment of active myocardites in children: hemodynamic evaluation

Objetivo Analisar parâmetros hemodinâmicos (fração de ejeção do ventrículo esquerdo (FEVE), índice cardíaco (IC), pressão média de capilar pulmonar (PCP) e diâmetro diastólico do ventrículo esquerdo (DdVE) em um grupo de crianças portadoras de miocardite ativa (MA), diagnosticadas através de biopsia endomiocárdica, submetidas à terapéutica convencional e a diferentes drogas imunossupressoras (prednisona isolada ou prednisona associada à azatioprina ou ciclosporina). Casuística e Métodos Quarenta e quatro crianças de um grupo de portadores de miocardiopatia dilatada de importante repercussão clínica. Vinte do sexo masculino e 22 do feminino, com idades entre 10 meses e 15 anos (mediana 1,3 anos). Foram submetidas a exames clínico e laboratoriais onde se obtiveram os parâmetros hemodinâmicos. Foram aistribuídas alternadamente em 4 grupos, de acordo com sua admissão no hospital e submetidos ao seguinte esquema terapêutico: grupo I (9 pacientes)medicação convencional (MC); grupo II(12 pacientes)MC + prednisona; grupo III(16 pacientes)MC + prednisona + azatioPrina; grupo IV (13 pacientes) MC + prednisona + ciclosporina. Os parâmetros foram obtidos pré e pós-tratamento, nos 4 grupos em estudo...

Purpose To analyse hemodynamic parameters (left ventricles ejection fraction, cardiac index, mean pulmonary wedge pressure and left ventricle diastolic diameter, in a group of children with active myocarditis (diagnosed by endomyocardial biopsy) pre and post treatment with conventional therapy and immunosuppressive drugs (isolated prednisone or prednisone associated with azathioprine or cyclosporine). Patients and Methods Forty-four pediatric patients with active myocarditis were studied. Twenty males and 24 females from 10 months to 15 years old (median = 1.3 years). All patients were submitted to hemodynamic study and endomyocardial biopsy. The hemodynamie parameters mentioned above were analysed before and after the proposed therapy. The patients were distributed in group according to the admission in the protocol, group I (9 pts)conventional therapy (CT); group II (12 pts)CT plus preanisone; group III (16 pts)CT plus prednisone plus azathioprine; group IV (13 pts)CT plus prednisone plus cyclosporine...