Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center

ABSTRACT Introduction: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported Methods: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed Results: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% Conclusion: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center.

INTRODUCTION: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported METHODS: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed RESULTS: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% CONCLUSION: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Wilms tumor in children: A multivariate analysis of prognostic factors, with emphasis on inferior vena cava/right atrium extension. Results from a single-center study.

BACKGROUND: To identify prognostic factors for overall survival through the analysis of 132 patients with Wilms tumor followed at a single center, with emphasis on the inferior vena cava/right atrium extension. METHODS: Retrospective analysis of overall survival using logistic regression models and including age, sex, clinical features, associated syndromes, comorbidities, tumor size before chemotherapy, stage, presence of metastatic disease and its site, invasion of adjacent structures, inferior vena cava/right atrium extension, laterality, tumor histology, chemotherapy protocol, and radiotherapy as potential risk factors. RESULTS: From January 2000 through November 2021, 132 patients met the inclusion criteria, 64 females and 68 males; 15 (11.4%) patients presented with tumoral extension to inferior vena cava/right atrium and 44 had metastatic disease (33.3%). Based on logistic regression, the factors correlating to a fatal outcome were male sex (p = 0.046), high risk histology (p = 0.036), and the presence of metastatic disease (p = 0.003). None of the patients presenting inferior vena cava/right atrium extension died (p = 0.992). In a specific analysis of metastatic sites, hepatic metastasis alone showed correlation with a fatal outcome (p = 0.001). CONCLUSION: These results underline the importance of identifying and treating metastatic disease and high-risk tumors. The female gender as a potential driver for a less aggressive disease is a new finding that deserves further investigation. The accurate identification of inferior vena cava/right atrium extension, subsequent preoperative chemotherapy, and resection with a skilled team promoted survival rates of all patients. LEVEL OF EVIDENCE: II.

Outcome of patients with stage IV high-risk Wilms tumour treated according to the SIOP2001 protocol: A report of the SIOP Renal Tumour Study Group.

INTRODUCTION: High-risk (HR) metastatic (stage IV) Wilms tumours (WTs) have a particular poor outcome. METHODS: Here, we report the results of HR (diffuse anaplastic [DA] or blastemal type [BT]) stage IV WT treated patients according to the HR arm in the SIOP2001 prospective study. RESULTS: From January 2002 to August 2014, 3559 patients with WT were included in the SIOP2001 trial. Among the 525 patients (15%) with metastatic WT, 74 (14%) had stage IV HR-WT. The median age at diagnosis was 5.5 years (range: 1.4-18.3). Thirty-four patients (47%) had BT-WT and 40 (53%) had DA-WT. Five-year event-free survival rates were 44 ± 17% and 28 ± 15% for BT-WT and DA-WT, respectively (p = 0.09). Five-year overall survival rates were 53 ± 17% and 29 ± 16% for BT-WT and DA-WT, respectively (p = 0.03). Metastatic complete response after preoperative treatment was significantly associated with outcome in univariate and multivariate analyses (hazards ratio = 0.3; p = 0.01). Postoperative radiotherapy of metastatic sites might also be beneficial. Forty-three of 74 patients experienced a relapse or progression predominantly in the lungs (80%). The median time to relapse/progression after diagnosis was 7.3 months (range: 1.6-33.3) and 4.9 months (range: 0.7-28.4) for BT-WT and DA-WT, respectively (p = 0.67). This is the first prospective evidence of inferior survival of stage IV BT-WT as compared with historical intermediate-risk WT. Survival of patients with stage IV DA-WT has not improved compared to the previous SIOP93-01 study. CONCLUSION: These results call for new treatment approaches for patients with HR stage IV WT.

Development of a continuous reactor for emulsion-based microencapsulation of hexyl acetate with a polyuria shell.

Microencapsulation is almost exclusively performed in batch processes. With today's chemistry increasingly performed in flow reactors, this work aims to realise a continuous reactor setup for the encapsulation of an ester with a polyuria (PU) shell. The generation of an emulsion template is performed in a recirculation loop driven by a pump and equipped with static mixers, screen type and Kenics®. Calorimetric measurements are performed to characterise the energy dissipation rate inside the loop. The curing step is performed in a coiled tube reactor with two geometric configurations. Number based capsule size distributions are derived from micrograph analysis. Results indicate that the recycle pump is the main contributor to determine the capsule size distribution. A continuous setup is achieved for PU microcapsules containing hexyl acetate with a production rate of 198 g/h dry capsules, and a mean capsule diameter of 13.3 µm with a core content of 54 wt%.

Immunoglobulin G4-related disease with recurrent uveitis and kidney tumor mimicking childhood polyarteritis nodosa: a rare case report.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an condition rarely reported in children. Additionally, IgG4-RD may rarely mimic vasculitis in adults and may infrequently present with uveitis. In our service, 6,198 patients were followed-up and only one (0.0001%) of them had IgG4-RD. To our knowledge, the present IgG4-RD case was the first mimicking childhood polyarteritis nodosa (c-PAN) with recurrent uveitis and kidney tumor. CASE REPORT: We describe herein a 7-year-old boy that presented intermittent fever. He developed arthralgia, weight loss, myalgia, skin lesions and recurrent uveitis. Skin biopsy revealed necrotizing vasculitis in medium/small sized vessels associated with septal panniculitis suggesting cPAN. Prednisone and azathioprine were administered with improvement. At 11 years, he had persistent fever and abdominal angiotomography revealed a large tumor in left kidney and he was then submitted to nephrectomy. The renal histopathology showed lymphoplasmacytic and histiocytic proliferation with extensive areas of fibrosis, and lymphomonocitic phlebitis with presence of IgG4 in 43 plasmocyte cells, suggesting IgG4-RD. DISCUSSION: we present herein a unique case of a male pediatric patient with IgG4-RD with rare ocular, cutaneous and renal manifestations.

Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations.

Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

The Influence of Income and Formal Education on Damage in Brazilian Patients With Systemic Lupus Erythematosus.

OBJECTIVE: The aim of this study was to evaluate the association of socioeconomic status and American College of Rheumatology/Systemic Lupus International Collaborating Clinics Damage Index (SDI) score in Brazilian patients with systemic lupus erythematosus (SLE). METHODS: Five hundred twenty-three patients (SLE ACR criteria) 18 years or older who were at 12 months or greater since diagnosis were included. Socioeconomic status was assessed by per-capita income and years of education. Race was categorized as white and nonwhite. The SDI and Mexican SLE Disease Activity Index were used. STATISTICAL ANALYSIS: Mean ± SD and median were used for descriptive analysis. Student t test, Mann-Whitney U test, χ test, and Spearman rank correlation coefficient and univariate and multivariate regression analyses were performed. The level of significance was set at 5% for all statistical tests. RESULTS: Ninety-six percent were female, 51.2% were nonwhite, and the mean age was 37.8 ± 1.4 years. Disease duration was 8.2 ± 10.3 years and formal education was 10.2 ± 3.5 years. Unemployment among patients was 63.7%, with median monthly per-capita income of US $276. Mean SDI score was 1.4 ± 1.52, and 65.6% had some type of damage (SDI ≥1). Patients with SDI of 1 or greater had lower income (P = 0.039). Nonwhite patients had higher SDI than did white patients (P = 0.005). The SDI presented a positive correlation with disease duration (P < 0.001) and age (P < 0.001) and a negative correlation with years of education (P = 0.001). Working patients had lower SDI than did inactive ones (P ≤ 0.001). In a multivariate analysis, older age, higher disease duration, nonwhite race, low income, and out-of-work profile were associated with damage. CONCLUSIONS: Besides nonmodifiable characteristics such as longer disease duration and older age, low income was also associated with damage. Therefore, interventions to give adequate socioeconomic support are necessary to improve outcome, mainly in poorer and nonwhite SLE patients.

Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment.

Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.

Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations / Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 1 - Diagnóstico e situações especiais

Abstract Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias. Até 2013, as Américas haviam registrado apenas casos importados quando, em outubro desse mesmo ano, foram notificados os primeiros casos na Ilha de Saint Martin, no Caribe. No Brasil, os primeiros relatos autóctones foram confirmados em setembro de 2014 e até a semana epidemiológica 37 de 2016 já haviam sido registrados 236.287 casos prováveis de infecção pelo chikungunya vírus (CHIKV), 116.523 confirmados sorologicamente. As mudanças ambientais causadas pelo homem, o crescimento urbano desordenado e o número cada vez maior de viagens internacionais têm sido apontados como os fatores responsáveis pela reemergência de epidemias em grande escala. Caracterizada clinicamente por febre e dor articular na fase aguda, em cerca de metade dos casos existe evolução para a fase crônica (além de três meses), com dor persistente e incapacitante. O objetivo deste trabalho foi elaborar recomendações para diagnóstico e tratamento da febre chikungunya no Brasil. Para isso, foi feita revisão da literatura nas bases de dados Medline, SciELO e PubMed, para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Foram geradas 25 recomendações, divididas em três grupos temáticos: (1) diagnóstico clínico, laboratorial e por imagem; (2) situações especiais e (3) tratamento. Na primeira parte estão os dois primeiros temas e o tratamento na segunda.

Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment / Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 2 - Tratamento

Abstract Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias, visto que metade dos casos evolui com artrite crônica, persistente e incapacitante. Os dados na literatura sobre terapêuticas específicas nas diversas fases da artropatia ocasionada pela infecção pelo vírus chikungunya (CHIKV) são limitados, não existem estudos randomizados de qualidade que avaliem a eficácia das diferentes terapias. Há algumas poucas publicações sobre o tratamento das manifestações musculoesqueléticas da febre chikungunya, porém com importantes limitações metodológicas. Os dados atualmente disponíveis não permitem conclusões favoráveis ou contrárias a terapêuticas específicas, bem como uma adequada avaliação quanto à superioridade entre as diferentes medicações empregadas. O objetivo deste trabalho foi elaborar recomendações para o tratamento da febre chikungunya no Brasil. Foi feita uma revisão da literatura com seleção de artigos baseados em evidência, nas bases de dados Medline, SciELO, PubMed e Embase e de resumos de anais de congressos, além da opinião dos especialistas para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Este artigo refere-se à parte 2 das Recomendações da Sociedade Brasileira de Reumatologia para Diagnóstico e Tratamento da Febre Chikungunya, que trata especificamente do tratamento.

New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years.

OBJECTIVE: The aim of this study was to summarize the experience of a tertiary center in treating hepatoblastoma for the last 21 years. PATIENTS AND METHODS: Fifty-eight cases were included. The tumor extent and prognosis were assessed using the PRETEXT system. The following data were analyzed: age at diagnosis, comorbidities, prematurity, treatment modalities, histopathological findings, surgical details and complications, treatment outcomes, chemotherapy schedules, side effects and complications. Treatment outcomes included the occurrence of local or distant recurrence, the duration of survival and the cause of death. The investigation methods were ultrasonography, CT scan, serum alpha-fetoprotein level measurement and needle biopsy. Chemotherapy was then planned, and the resectability of the tumor was reevaluated via another CT scan. RESULTS: The mean numbers of neoadjuvant cycles and postoperative cycles of chemotherapy were 6±2 and 1.5±1.7, respectively. All children except one were submitted for surgical resection, including 50 partial liver resections and 7 liver transplantations. Statistical comparisons demonstrated that long-term survival was associated with the absence of metastasis (p=0.04) and the type of surgery (resection resulted in a better outcome than transplantation) (p=0.009). No associations were found between vascular invasion, incomplete resection, histological subtype, multicentricity and survival. The overall 5-year survival rate of the operated cases was 87.7%. CONCLUSION: In conclusion, the experience of a Brazilian tertiary center in the management of hepatoblastoma in children demonstrates that long survival is associated with the absence of metastasis and the type of surgery. A multidisciplinary treatment involving chemotherapy, surgical resection and liver transplantation (including transplantations using tissue from living donors) led to good outcomes and survival indexes.

New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years

OBJECTIVE: The aim of this study was to summarize the experience of a tertiary center in treating hepatoblastoma for the last 21 years. PATIENTS AND METHODS: Fifty-eight cases were included. The tumor extent and prognosis were assessed using the PRETEXT system. The following data were analyzed: age at diagnosis, comorbidities, prematurity, treatment modalities, histopathological findings, surgical details and complications, treatment outcomes, chemotherapy schedules, side effects and complications. Treatment outcomes included the occurrence of local or distant recurrence, the duration of survival and the cause of death. The investigation methods were ultrasonography, CT scan, serum alpha-fetoprotein level measurement and needle biopsy. Chemotherapy was then planned, and the resectability of the tumor was reevaluated via another CT scan. RESULTS: The mean numbers of neoadjuvant cycles and postoperative cycles of chemotherapy were 6±2 and 1.5±1.7, respectively. All children except one were submitted for surgical resection, including 50 partial liver resections and 7 liver transplantations. Statistical comparisons demonstrated that long-term survival was associated with the absence of metastasis (p=0.04) and the type of surgery (resection resulted in a better outcome than transplantation) (p=0.009). No associations were found between vascular invasion, incomplete resection, histological subtype, multicentricity and survival. The overall 5-year survival rate of the operated cases was 87.7%. CONCLUSION: In conclusion, the experience of a Brazilian tertiary center in the management of hepatoblastoma in children demonstrates that long survival is associated with the absence of metastasis and the type of surgery. A multidisciplinary treatment involving chemotherapy, surgical resection and liver transplantation (including transplantations using tissue from living donors) led to good outcomes and survival indexes. .

Chemistry of crosslinking processes for self-healing polymers.

Recent developments in material design have seen an exponential increase of polymers and polymer composites that can repair themselves in response to damage. In this review, a distinction is made between extrinsic materials, where the self-healing property is obtained by adding healing agents to the material to be repaired, and intrinsic materials, where self-healing is achieved by the material itself through its chemical nature. An overview of the crosslinking chemistries used in self-healing materials will be given, discussing the advantages and drawbacks of each system. The review is not only aiming to enable researchers to compare their ongoing research with the state-of-the-art but also to serve as a guide for the newcomers, which allows for a selection of the most promising self-healing chemistries.

P-glycoprotein expression, tumor weight, age, and relapse in patients with stage I and II favorable-histology Wilms' tumor.

Fifteen percent of patients with Wilms' tumor (WT) experience relapse. It has been suggested that weight and age may affect the chances of relapse. Few studies have investigated the role, if any, between P-glycoprotein (P-gp) and relapse. The authors assessed the prognostic value of tumor weight and age at diagnosis and asked whether some other potential biological markers, specifically P-gp protein expression, had a prognostic value in favorable-histology WT. No association between age and relapse could be found. Patients with tumor weight ≥550 g were 6 times more likely to relapse, whereas P-gp expression was positive in 18/40 (45%) of the patients, of which 10/12 (83.3%) relapsed and 8/28 (28.6%) did not. Further studies are necessary to elucidate whether or not P-gp is related to relapse in patients with histologically favorable Wilms' tumor. If confirmed, the protein may be used in the future as a target for new drugs and treatments for this group of patients.

P-glycoprotein expression, tumor weight, age, and relapse in patients with stage I and II favorable-histology Wilms' tumor

Fifteen percent of patients with Wilms' tumor (WT) experience relapse. It has been suggested that weight and age may affect the chances of relapse. Few studies have investigated the role, if any, between P-glycoprotein (P-gp) and relapse. The authors assessed the prognostic value of tumor weight and age at diagnosis and asked whether some other potential biological markers, specifically P-gp protein expression, had a prognostic value in favorable-histology WT. No association between age and relapse could be found. Patients with tumor weight ¡Ý550 g were 6 times more likely to relapse, whereas P-gp expression was positive in 18/40 (45%) of the patients, of which 10/12 (83.3%) relapsed and 8/28 (28.6%) did not. Further studies are necessary to elucidate whether or not P-gp is related to relapse in patients with histologically favorable Wilms' tumor. If confirmed, the protein may be used in the future as a target for new drugs and treatments for this group of patients

Unraveling mechanistic events in solids-stabilized emulsion polymerization by monitoring the concentration of nanoparticles in the water phase.

The fate of nanoparticles used as stabilizers in solids-stabilized, or Pickering, emulsion polymerization for the formation of armored hybrid polymer latexes was studied. We showed that disk centrifugation can be used as a powerful quantitative tool to analyze and determine the concentration of nanoparticles in the water phase throughout solids-stabilized emulsion polymerizations. We performed a series of emulsion polymerizations using vinyl acetate, vinyl pivalate, methyl methacrylate, or butyl acrylate in presence of silica nanoparticles (Ludox TM-40, ca. 25 nm in diameter). The developed method to quantify the number of silica nanoparticles in the water phase proved to be an invaluable tool for determining key features of the polymerization process. The obtained concentration profiles versus monomer conversion explained the existence of limited coalescence of armored particles in the later stages of the solids-stabilized emulsion polymerization process of vinyl acetate, leading to nonspherical structures. Moreover, we demonstrated that the correlation of the measured number of silica nanoparticles present in the water phase with the average particle sizes of the latex particles provided excellent predictions for the coverage of the armored layer of nanoparticles on the surfaces of the polymer particles, corresponding to observed packing patterns.

TP53 mutation profile of esophageal squamous cell carcinomas of patients from Southeastern Brazil.

Esophageal cancer (EC) is among the 10 most common and fatal malignacies in the world, presenting a marked geographic variation in incidence rates between and within different countries. The TP53 tumor suppressor gene is highly mutated in esophageal tumors and its mutation pattern can offer clues to the etiopathology of the tumor. As Brazil presents one of the highest incidence areas in the West, a deeper knowledge of the molecular mechanisms related to EC development in the Brazilian population is needed. We analyzed the mutation profile of 110 esophageal squamous cell carcinomas (ESCC) of patients from Southeastern Brazil (Rio de Janeiro and São Paulo) and collected data regarding alcohol intake and tobacco smoking. We detected 41 mutations in tumor samples from 38 patients. There was no association between mutation frequency and tobacco smoking or alcohol drinking. The most frequently mutated codons were 179, 214, 220 and 248. Codons 179, 220 and 248 are hot-spots for ESCC, but codon 214 presents only 0.7% of the mutations registered in the IARC database. The mutation profile revealed a high percentage of mutations at A:T base pairs (34.1%) followed by deletions (17.1%). We concluded that the mutation profile detected in this study is different from that of patients from Southern Brazil but very similar to that previously seen in French patients, being characterized by a high frequency of mutations at A:T base pairs, which may be associated with acetaldehyde, the metabolic product of ethanol.

Linfoma de Hodgkin na infância e adolescência: 15 anos de experiência com o protocolo DH-II-90 / Hodgkin's lymphoma in children and adolescents: 15 years of experience with the DH-II-90 protocol

O desafio do tratamento do linfoma de Hodgkin na infância reside na redução da toxicidade aguda e tardia sem afetar os bons resultados terapêuticos. Crianças e adolescentes portadores de linfoma de Hodgkin recém-diagnosticado foram tratados com o protocolo institucional DH-II-90. Os objetivo deste trabalho foram: 1)avaliar as taxas de sobrevida global (SG) e livre de eventos (SLE) do protocolo DH-II-90 aplicado a portadores de LH; 2)avaliar as taxas de SG e SLE conforme estádio, idade, tumor "bulky", massa mediastinal, sintomas B, dose de radioterapia e 3)descrever os efeitos tardios. Sessenta e oito pacientes portadores de LH recém-diagnosticado, com idade entre 0 e 21 anos (idade mediana 9 anos, 20F:48M), foram tratados com quimioterapia (baixo risco:ABVD; alto risco:ABVD+MOP/COP) e radioterapia. O estadiamento foi distribuído desta forma: nove (13,2 por cento) estádio I A; 29 (42,6 por cento) II A; cinco (7,4 por cento) II B; nove (13,2 por cento) III A; dez (14,7 por cento) III B; dois (2,9 por cento) IV A e quatro (5,9 por cento) IV B. A SG em dez anos foi de 96,1 por cento ± 3,8 para o grupo de baixo risco e 93,3 por cento ± 4,5 para o de alto risco (p:0,402). A SLE foi de 88,9 por cento ± 5,2 em dez anos para o de alto risco e 86,5 por cento ± 6,3 para o de baixo risco (p: 0,969). A presença de massa mediastinal e doses de radioterapia maiores que 2100 cGy (p= 0,020 e p= 0,014, respectivamente) apresentam impacto negativo na SLE e a doença estádio I tem impacto positivo na SLE. Disfunção e carcinoma de tireoide são os efeitos tardios mais frequentes neste grupo de doentes. O protocolo DH-II-90 obteve resultados terapêuticos favoráveis, porém as taxas de complicações tardias, embora aceitáveis, demandam revisão do programa terapêutico.

The challenge of new protocols for Hodgkin's lymphoma (HL) treatment is to decrease the toxicity without impairing the results. The DH-II-90 protocol was designed to treat children and adolescents with HL. The objectives of this work were: 1) to assess the overall and event free survival of patients with newly diagnosed HL treated with the DH-II-90 protocol, 2) to assess the overall and event free survival by stage, age, presence of bulky disease, mediastinal mass, B symptoms, dose and type of radiotherapy, and 3) to describe late effects, data collected from the patients' charts. Sixty-eight patients with HL, from 0 to 21 years of age (median age 9 yr, 20F:48M) were treated with ABVD and involved-field radiotherapy for low-risk patients, and ABVD plus MOP or COP and extended field radiotherapy for high-risk patients. Stage distribution was: nine (13.2 percent) stage I A; 29 (42.6 percent) II A; five (7.4 percent) II B; nine (13.2 percent) III A; ten (14.7 percent) III B; two (2.9 percent) IV A and four (5.9 percent) IV B. The 10-year overall survival was 96.1 percent ± 3.8 percent for the low-risk group and 93.3 percent ± 4.5 percent for the high-risk group (p= 0.402). The 10-year event free survival was 88.9 percent ± 5.2 percent for high-risk and 86.5 percent ± 6.3 percent for low-risk patients (p= 0.969). The presence of mediastinal mass and more than 2100 cGy radiation doses had negative impact on event free survival (p= 0.020 and p= 0.014, respectively).Thyroid gland dysfunction was frequently observed and there were two cases of thyroid carcinoma. The DH-II-90 protocol is effective, but, due to the late effects presented by this group of patients, further modifications of the therapy schedule are required.