Sit less and move more! A cross-sectional study of the associations between physical activity and sedentary behaviors with inhibitory control in Brazilian adults.

OBJECTIVE: To investigate the independent and joint associations between sedentary behaviors (SB) and physical activity (PA) with inhibitory control (IC) in adults. METHODS: A total of 111 participants (median age = 30 years; 60% women), completed the Stroop Color-Words test to assess IC. They also wore accelerometers for seven days to measure SB, light PA, moderate-to-vigorous PA (MVPA), and daily steps. We previously set cutoff points for SB and PA measurements and tested them to determine their association with IC. All analyses were adjusted for potential confounding factors including age, gender, post-secondary education, income, body mass index, and accelerometer wear time. RESULTS: Low SB, high MVPA, and high daily steps were independently associated with a better IC compared to their respective counterparts. Adults with low levels of SB and light PA demonstrated better IC performance (ß = -227.67, 95%CI = -434.14 to -21.20) compared to those with high SB and low light PA. Conversely, individuals with high SB and high light PA exhibited worse performance (ß = 126.80, 95%CI = 2.11 to 251.50) than those in the high SB and low light PA group. Furthermore, the joint association of low SB with high MVPA (ß = -491.12, 95%CI = -689.23 to -293.01) or low SB with high daily steps (ß = -254.29, 95%CI = -416.41 to -92.16) demonstrated better IC performance compared to those with high SB and low MVPA or low daily steps. CONCLUSION: Our findings highlight independent and joint associations between low SB, high MVPA, and high daily steps with enhanced IC in adults.

Exercise behavior patterns and associations with subjective well-being during the COVID-19 pandemic: A cross-sectional study in Brazil.

INTRODUCTION: The COVID-19 pandemic has affected the behavior and practice of planned and structured physical exercises. This study aimed to investigate the association between changes in physical exercise behavior and subjective well-being during the COVID-19 pandemic in Brazil. METHODS: This cross-sectional study was performed in Brazil and included a total of 595 individuals recruited through social media platforms, personal and professional contacts. Each participant responded to self-completed questionnaire via an online survey between March 29 and May 7, 2020. The characteristics of physical exercise (frequency, intensity, and duration) were collected before and during the pandemic. The subjective state of mood was measured through the Profile of Mood States (POMS) questionnaire during the pandemic. A generalized linear model was employed for the analysis. RESULTS: Exercising during the pandemic only promoted protective effects on the subjective mood. An exercise frequency of 3-5 days/week was associated with improved vigor and between 6-7 days/week with improved vigor and total mood when compared to not exercising at all (p < .005). A moderate intensity was associated with improved vigor, and a high intensity with improved vigor, total mood, and less fatigue in comparison to low-intensity exercise programs (p < 0.05). Maintaining the same duration of exercise sessions during the pandemic was associated with lower scores of depression/anxiety, fatigue and irritability, and improved vigor and total mood, while performing longer sessions with improved vigor when compared to short exercise sessions (p < .005). CONCLUSION: Regular exercising during the pandemic promotes positive changes in the subjective well-being. Our results reinforce the need for adopting and maintaining a physical exercise routine during the COVID-19 pandemic as a protective effect on mental health.

High prevalence of HIV-associated neurocognitive disorders (HAND) in São Paulo City, Brazil / Alta prevalência de desordem neurocognitiva associada ao HIV (HAND) na Cidade de São Paulo, Brazil

INTRODUCTION: HIV-associated neurocognitive disorders (HAND) are the subject of many studies, some of them reporting a prevalence of up to 50 percent. OBJECTIVES: To determine the prevalence and factors associated with HIV neurocognitive disorders (HAND) in a cohort of HIV-1-infected patients in São Paulo city, Brazil. METHODOLOGY: Descriptive cross-sectional study including 106 HIV-1-infected patients, employing direct interview and neuropsychological tests, applied by trained neuro-psychologists with expertise in the tests. Other, similar assessment tools we used were Brief Neurocognitive Questionnaire, International HIV Dementia Scale, Lawton Instrumental Activities of Daily Living, Hospital Anxiety and Depression Scale, Social Support Scale for People with HIV/Aids, Assessment of Adherence to Antiretroviral Therapy Questionnaire, and a complex neuropsychological assessment. RESULTS: We included 106 patients from May 2015 to April 2018. We found a high prevalence of HAND in our patients (45%), with 27.5% presenting asymptomatic neurological impairment (ANI) and 17.5% mild neurological dysfunction (MND); only one patient presented HIV-associated dementia (HAD) (0.9%). Women were more likely to have MND (52.9%) and the only case of HAD was also female. The high prevalence of neurocognitive disorders was independent of the immunological status, use of efavirenz, or virological control. CONCLUSIONS: This study may mirror the national and international scenarios, showing a high prevalence of HAND (45%) and the prevalence of some risk factors, in special among women

INTRODUÇÃO: As doenças neurocognitivas associadas ao HIV (HAND), são o assunto de muitos estudos, alguns deles relatando uma prevalência de até 50 por cento. OBJETIVOS: Determinar a prevalência e os fatores associados aos distúrbios neurocognitivos do HIV (HAND) em uma coorte de pacientes infectados pelo HIV-1 na cidade de São Paulo, Brasil. METODOLOGIA: Estudo transversal descritivo incluindo 106 pacientes infectados pelo HIV-1, utilizando entrevista direta e testes neuropsicológicos, aplicados por neuropsicólogos treinados com experiência nos testes. Foram utilizados também: Questionário Neurocognitivo Breve, Escala Internacional de Demência do HIV, Atividades Instrumentais de Vida Diária de Lawton, Escala Hospitalar de Ansiedade e Depressão, Escala de Apoio Social para Pessoas com HIV / Aids, Avaliação da Adesão à Terapia Antiretroviral Questionário e uma bateria de avaliação neuropsicológica complexa. RESULTADOS: Foram avalaidos 106 pacientes de maio de 2015 a abril de 2018. Foi observado uma alta prevalência de HAND em nossos pacientes (45%), com 27,5% apresentando comprometimento neurológico assintomático (ANI) e 17,5% comprometimento cognitive leve (MND); apenas um paciente apresentou demência associada ao HIV (DAH) (0,9%). As mulheres eram mais propensas a ter MND (52,9%) e o único caso de HAD também era do sexo feminino. A alta prevalência de distúrbios neurocognitivos foi independente do estado imunológico, uso de efavirenz ou controle virológico. CONCLUSÕES: Este estudo pode espelhar o cenário nacional e internacional, mostrando uma alta prevalência de HAND (45%) e a prevalência de alguns fatores de risco, em especial entre as mulheres

Echocardiographic evaluation in Dorper ovine fetuses: Applications and limitations.

In this study we aim to show the application of ultrasound evaluation of the fetal heart in the ovine species, as well as its limitations in the field. Ten Dorper sheep, without any sedation, were evaluated starting from the second month of pregnancy through transabdominal ultrasound with an ultrasound device equipped with a convex transducer. Images of the fetal heart were obtained through maternal abdominal ultrasound by identifying the position of the fetus and conducting the following measurements: length and diameter of the heart, dimensions of the right and left ventricles and dimensions of the right and left atria. The measurements could only be conducted with acceptable precision starting from the third month of pregnancy. There was a significant difference only for left ventricle diameter, which was larger in the fifth month of pregnancy. The echocardiographic evaluation of the fetus enables monitoring the heart development identifying early fetal viability, assessing inadequate events that could put the pregnancy at risk, especially for production animals. For the experimental design of research employing production animals, it is important to consider, among other factors, the limitations of the evaluation on the field, such as restraining the animals, the stress caused by handling and environmental conditions, temperature, luminosity, facilities available and the qualifications of the team.

Heart rate variability in Dorper sheep in the fetal and neonatal periods until 120 days of age: Use of the technique in the field.

The evaluation of the autonomic cardiac functions may be performed through the analysis of the heart rate variability. Heart rate variability is defined as the fluctuations in the heart rhythm or rate, and represents a useful tool in the evaluation of the autonomic nervous system through the sympathetic and parasympathetic components, as well as its balance and its reflexes on the cardiorespiratory control system. Fetal electrocardiography provides important information regarding the well-being of the fetus since, in human fetuses, there are changes in the behavior of the fetal heart rate during the second and third trimesters of pregnancy due to an increase in parasympathetic activity. Therefore, considering the importance of evaluating fetal viability, this study aims at evaluating the behavior of fetal heart rate and heart rate variability in Dorper sheep, as well as the activity of the autonomic nervous system during fetal life and in newborn lambs. The species is often used in experimental studies and autonomic nervous system activity is a prognostic index, therefore, the diagnosis of modifications in the sympathovagal balance may represent an early index for fetal viability and well-being in lambs. The analyses were performed in 10 Dorper sheep during pregnancy and in 10 lambs after birth until 120 days of age. There was a decrease in the fetal heart rate and heart rate variability indexes during the fifth month of pregnancy, but without statistical significance for the period evaluated. The heart rate of the lambs decreased gradually until they were 21 days old. The indexes SDNN (standard deviation of RR intervals) and RMSSD (square root of the mean of successive differences between adjacent RR intervals) diverged according to age, being high at day 60. Fetal viability is relevant in sheep fetuses to avoid losses during pregnancy and risks to the health of the mother. In the species, there seems to be a predominance of parasympathetic activity starting from the 21st day of age. Heart rate variability may be employed as a tool in the evaluation of the fetus and development of lambs, since changes in its behavior may represent an adverse effect to fetal and neonatal health.

Developmental Stuttering Screening Instrument: development and content validation / Instrumento de Rastreio para a Gagueira do Desenvolvimento: elaboração e validação de conteúdo

ABSTRACT Purpose: to develop a screening instrument to identify the risk of developmental stuttering in preschoolers. Methods: the procedures were divided into two stages: The first one (theoretical), consisted of the literature review and the construction of the items that make up the instrument; the second stage (content validation), consisted of the analysis of the instrument by a judging committee formed by 10 speech-language-hearing therapists who work in the field of fluency. The data analysis was based on the calculation of the item content validity index (I-CVI) and the total number of answers (T-CVI). Also, an item reliability analysis was conducted with Cronbach's alpha. Results: the Developmental Stuttering Screening Instrument (DSSI) encompassed 24 items distributed into four key categories. The I-CVI and T-CVI revealed a high agreement between the judges. The Cronbach's alpha coefficients indicated a high internal consistency between the judges' answers in 19 of the 24 items. The qualitative analysis pointed to the need for new adjustments. All the analyses contributed to the construction of the second version of the instrument. Conclusion: the proposed instrument showed content-based validity evidence that made it possible, up to the present moment, to adjust it to its construct. It is suggested that the validation process continue, employing new accuracy measures.

RESUMO Objetivo: elaborar um instrumento de rastreio com fins de identificação do risco para gagueira do desenvolvimento em crianças pré-escolares. Métodos: os procedimentos foram divididos em duas etapas: A primeira etapa - teórica, consistiu na revisão da literatura e a construção dos itens que compõe o instrumento; A segunda etapa - validação de conteúdo, consistiu da análise do instrumento por um comitê de juízes composto por 10 fonoaudiólogas atuantes na área da Fluência. Para análise dos dados foi calculado o índice de validade de conteúdo por item (IVC-I) e pelo total de respostas (IVC-T), bem como realizada uma análise da confiabilidade dos itens por meio do alfa de Cronbach. Resultados: o Instrumento de Rastreio para a Gagueira do Desenvolvimento (IRGD) foi composto por 24 itens distribuídos em quatro categorias-chaves. Os índices IVC-I e IVC-T evidenciaram alta concordância entre os juízes. Os coeficientes do alfa de Cronbach indicaram alta consistência interna entre as respostas dos juízes em 19 dos 24 itens. A análise qualitativa destacou a necessidade de novos ajustes. Todas as análises possibilitaram a construção da segunda versão do instrumento. Conclusão: o instrumento proposto mostrou evidências de validade baseada no conteúdo que permitiram, até o momento, ajustá-lo em relação ao seu construto. Sugere-se a continuidade do processo de validação por meio do emprego de novas medidas de acurácia.

Developmental Stuttering Screening Instrument: evidence of sensitivity and accuracy measures

ABSTRACT Purpose: to verify the sensitivity and accuracy measures of the Developmental Stuttering Screening Instrument (DSSI). Methods: the DSSI was administered to 30 parents/guardians of children aged 2 to 5 years and 11 months with and without complaint of stuttering. The instrument administration was timed. The sensitivity analysis used the Weight of Evidence (WoE) binary classification model to verify the strength level of the items. The cutoff scores were established with grouping analysis with the k-means cluster method, based on the minimum and maximum values of each identified group's scores. The data were analyzed with the SPSS statistical software (version 20.0) and were considered significant with p ≤ 0.05. Results: the interviews lasted an overall mean of 17 minutes. The WoE model revealed that the items with the greatest predictive strength for risk of stuttering were the social reaction to their speech, the physical concomitants, and the comprehension of the child's speech. The correspondence analysis showed a strong association between "having complaints" and "high total score", as well as between "not having complaints" and "low total score", indicating that the parents' complaints are a factor that leads to high scores in the instrument. "Sex" had little predictive effect for risk. The grouping analysis enabled the stratification of subjects into three risk levels: "not at risk", "under observation", and "at risk". Conclusion: the instrument presented the first evidence of sensitivity and accuracy measures, thus, making the identification of risk of developmental stuttering in preschoolers, possible.

Evaluation of heart rate variability and behavior of electrocardiographic parameters in dogs affected by chronic Monocytic Ehrlichiosis.

Canine Monocytic Ehrlichiosis (CME) is a systemic disease prevalent in the entire world caused by the obligate intracellular bacteria Ehrlichia canis. The occurrence of myocarditis with a high prevalence of arrhythmias in dogs affected by this disease in the cytopenic phase has already been proven. This study aims to evaluate the concentrations of CK MB, cTnI and NT-proBNP in dogs affected by Ehrlichia canis in the chronic phase since the intense stimulation of the immune system can lead to myocarditis; to evaluate if the condition can lead to arrhythmic events and, if so, define their frequency and classification through conventional and ambulatory electrocardiogram tests (Holter method) for a period of 24 hours; to analyze heart rate variability in the time domain and whether the condition can lead to autonomic imbalance; and to determine the survival rate of affected dogs, identifying possible risk factors for mortality at this stage of the disease. For this purposes, we evaluated clinical, hematological and biochemical data, as well as the concentrations of cardiac biomarkers Creatine Kinase-MB (CK MB), Cardiac Troponin I (cTnI) and N-terminal pro-peptide natriuretic type B (NT-proBNP). We also analyzed conventional and ambulatory electrocardiography (24-hour Holter) and heart rate variability (HRV) in 20 dogs afflicted by cytopenic CME in the chronic phase of the disease (G1) and compared the results with a control group comprised of ten healthy dogs (G2). G1 was monitored during the treatment for 28 days, during which eight (8) of the 20 infected dogs died (40%). Anorexia, vomiting, fatigue, hypoalbuminemia, heart murmurs and increased concentrations of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were common clinical signs. The mean concentrations of cTnI and CKMB were significant (0.24 ng / mL ± 0.5, 229 ± 205 IU / mL) in comparison to the control group (0.042 ± 0.07 ng / mL, 126 ± 46.12 IU / mL). No significant differences were observed between NT-proBNP concentrations in G1 (135.46 ± 29.7) and G2 (138.28 ± 19.77). Nine of the twenty dogs (45%) presented a high frequency of arrhythmias during 24-hour recording, ranging from first and second-degree atrioventricular block, ventricular and supraventricular ectopic events and sinus tachycardia. No sinus pause was observed. One dog had 120 episodes of unsustained ventricular tachycardia and two episodes of sustained ventricular tachycardia. The short-term and long-term HRV data, represented by SDNN (ms), SDANN (ms) and pnn50 (%) were also significant lower (83 ± 65, 56.05 ± 37.3 and 14.56 ± 20, respectively) in comparison to the healthy animals (268 ± 74.6, 168.3 ± 39.14 and 55.87 ± 12.8, respectively). These results suggest that cytopenic CME is characterized by an arrhythmogenic component and intense stimulation of the sympathetic autonomic nervous system in the heart, reflecting an imbalance in the activity of the ANS.

Conventional and Holter Electrocardiographic Assessment of Dogs Infected Naturally With Acute Canine Monocytic Ehrlichiosis.

Canine Monocytic Ehrlichiosis (CME) is a disease of worldwide distribution caused by the bacteria Ehrlichia canis, appearing primarily in hot climates due to the massive prevalence of its vector, the tick Rhipicephalus sanguineus. Previous studies have shown that dogs afflicted by CME in the chronic phase can develop infectious myocarditis, arrhythmias, and alterations in heart rate variability (HRV), but there are few studies correlating cardiac diseases with the acute phase of CME. This study aims at assessing electric cardiac alterations and HRV in the time and frequency domains during the acute phase of CME. This study assessed 22 animals divided into 2 distinct groups: the control group, comprised by 10 healthy dogs, and the sick group, comprised of 12 dogs infected naturally with ehrlichiosis which presented clinical and hematological signs compatible with the acute phase of the disease. The animals underwent conventional and Holter electrocardiographic evaluations, systolic blood pressure measurement, complete blood count and biochemical assays (urea, creatinine, alanine aminotransferase (ALT), alkaline phosphatase (AP), and gamma glutamyl transferase (GGT)). The sick group presented higher activity in the sympathetic nervous system than in the parasympathetic nervous system, manifest as a significant increase in mean heart rate and a reduction in the HRV indexes for the time and frequency domains. The frequency-domain HRV indexes presented sympathetic prevalence during the sleep and vigilance states. Sinus tachycardia was the predominant heart rhythm in 58.33% of the animals. The mean systolic blood pressure diverged between the groups and no significant arrhythmias were observed during monitoring. The serum concentrations of urea, creatinine, AP, ALT, and GGT were within the established reference values for the species. We observed no indication that there was enough time during the acute phase for the disease to evolve in a way that resulted in arrhythmias, as is common in the chronic phase, but we observed that animals in the acute phase already present reduced HRV indexes.

Intestinal parasitic infections in a lowincome urban community: prevalence and knowledge, attitudes and practices of inhabitants of Parque Oswaldo Cruz, Rio de Janeiro, Brazil

Intestinal parasitic infections (IPIs) are present in Brazil from upper-to low-income communities, with varying infection estimates; however, they affect those living in urban and rural poverty more severely, without adequate access to consistently safe drinking water, sanitation, waste disposal, medical access and education. Estimates show the need for establishing infection prevalence and socioeconomic features, along with population knowledge, attitudes and practices (KAP) regarding IPIs. The purpose of this study is to assess the prevalence and KAP regarding IPIs of residents of an urban low-income community (Parque Oswaldo Cruz/Amorim) of the Complexo de Manguinhos, Rio de Janeiro, Brazil. The Lutz sedimentation technique was used for parasite detection (n=1,121) and, to obtain data on community KAP regarding IPIs, a KAP survey, adapted from Mello et al. was applied (n=505). An overall prevalence of 20.7% was detected with protozoa composing 92.9% (n=235) of the positive samples. Questionnaires revealed generally correct knowledge but with several inconsistencies, unawareness of the association between the etiological agent and the disease, and uncertainty regarding own knowledge of the subject. The population understood the importance of prevention and was willing to utilize prevention strategies despite being unsure of how to prevent infection. Further studies are required to investigate best practices for improving health equity, community health empowerment and IPIs prevention in Rio de Janeiro, Brazil.

Gestión del riesgo biológico y su integración con la Seguridad y Salud del Trabajo en el Centro de Inmunología y Biopreparados de Cuba / Biohazard management and its integration into Labor Health at the Immunology and Bioproducts Centre in Cuba

La evaluación de riesgos es útil para planificar y mejorar la Seguridad Biológica, el control de la calidad y la Seguridad y Salud en el Trabajo, considerando el marco legal vigente en Cuba y la inspección constituye una parte importante de estos procesos. Con el objetivo de identificar y evaluar el riesgo biológico en el Centro de Inmunología y Biopreparados se realizó esta investigación. La misma incluyó la identificación del riesgo biológico en tres áreas, la evolución de inspecciones de Seguridad Biológica y las medidas correctivas recomendadas. Los resultados permitieron diseñar e implementar el Reglamento de Seguridad en el se integraron las funciones de Seguridad Biológica y Seguridad y Salud en el Trabajo (AU)

Risk assessments are useful to plan and improve biological safety, quality control and in general health and safety at work, taking into account the legal framework in Cuba. Supervision is an important part of these processes. Research was done in order to identify and to evaluate the biohazard in the Immunology and Bioproducts Centre (CIBHO). It included the identification and risk assessment in three areas, the biological safety supervisions and its evolution and the corrective measures recommended. The results allowed to design and to implement a Safety Regulation which includes measures for biological safety and health and safety at work (AU)

A phase I study of 5-fluorouracil/leucovorin and arsenic trioxide for patients with refractory/relapsed colorectal carcinoma.

PURPOSE: This Phase I study was designed to determine a safe combination dose of 5-fluorouracil (5-FU) and arsenic trioxide (ATO) to treat 5-FU-resistant relapsed/refractory colorectal cancer patients. We studied the effect of ATO in the downregulation of thymidylate synthase (TS) in peripheral blood mononuclear cells and in tumor biopsies. EXPERIMENTAL DESIGN: ATO was administered for 5 consecutive days during the first week and twice during weeks 2 to 3 and once on week 4. 5-FU/leucovorin (LV) was administered on days 8, 15, and 22. A modified accelerated titration design was used. 5-FU was dose escalated first followed by a planned dose increase for ATO. RESULTS: No dose-limiting toxicities were seen in seven patients who received 0.15 mg/kg ATO; grade 3 toxicities were as follows: neutropenia 1, diarrhea 1, and bowel obstruction 1. In patients receiving 0.20 mg/kg ATO, grade 3 toxicities were QTc prolongation 1, fatigue 4, alkaline phosphatase elevation 2, diarrhea 2, and peripheral edema 1. TS gene expression in peripheral blood mononuclear cell decreased in all patients. Eight tumors were biopsied, four showed TS downregulation, three showed upregulations, and one did not change. Estimated median progression-free survival and overall survival were 3.1 and 13.9 months, respectively. In patients who showed TS increase or no change versus TS reduction, estimated median progression-free survival was 2.6 versus 7.9 months (P = 0.188) and overall survival was 8.6 versus 11.7 months (P = 0.44), respectively. CONCLUSIONS: Thus, we determined 0.20 mg/kg ATO, 2,600 mg/m(2) 5-FU, and 500 mg/m(2) leucovorin (LV) to be the recommended phase II dose.

Methodological challenges in intervention studies.

Parental substance abuse is a risk factor for child maltreatment, neglect and multi-generational drug abuse. Developing efficacious, cost-efficient interventions is critical to addressing this growing problem. This article by Brian Porter, Luz Porter, Virginia McCoy, Mayra Lima, Clare Pryce and Sachin Nunnewar highlights lessons learned during the first year of a study based in Florida to evaluate a novel parenting intervention targeting substance-abusing mothers and their babies.

A phase II study of irinotecan, high-dose 24-h continuous intravenous infusion of floxuridine and leucovorin (IFLUX) for advanced, previously untreated colorectal cancer.

Our objectives were to determine response rate, time to progression, overall survival and tolerability of novel combination chemotherapy, consisting of irinotecan, high-dose 24-h continuous intravenous infusion of floxuridine and leucovorin in advanced previously untreated colorectal cancer. Thirty-eight patients with advanced colorectal cancer were treated at Sylvester Comprehensive Cancer Center, University of Miami, from 2000 to 2004, and received weekly intravenous infusion of irinotecan at 110 mg/m with a combination of 120 mg/kg floxuridine and 500 mg/m leucovorin administered as a 24-h continuous intravenous infusion. The treatment cycle consisted of 4 weeks of consecutive therapy followed by 2 weeks of rest. Five (13%) patients achieved complete response, 10 (26%) patients achieved partial response, 17 (45%) patients attained stable disease and six (16%) patients progressed. The overall response rate was 39% in this study. This chemotherapy regiment was well tolerated; the most common grade 3 toxicities were neutropenia (16%), anemia (16%), vomiting (24%), diarrhea (16%), and hand-and-foot syndrome (26%). The median time to progression was 11.5 months (347.5 days) with 95% confidence intervals of 6.8-12.9 months (206-389 days). The time to progression ranged from 1.8 to 34 months. The median survival of the patients in this trial was 31.28 months (952 days) with a confidence interval of 20.9-38.0 months (629-1141 days). Intravenous infusion of floxuridine and leucovorin is beneficial as first-line therapy in advanced colorectal cancer, demonstrating a prolonged time to progression and overall survival with acceptable tolerability and manageable toxicity profile.

Neoadjuvant, surgery and adjuvant chemotherapy without radiation for esophageal cancer.

BACKGROUND: A phase II trial to evaluate neoadjuvant (NAD), surgery and adjuvant (AD) combination chemotherapy without radiation therapy (RT) for patients with esophageal adenocarcinoma staged with endoscopic ultrasound and CT as T3N1 was carried out. METHODS: Thirty-three eligible patients were enrolled. NAD therapy was administered in two 49-day cycles and included cisplatin, floxuridine, paclitaxel and leucovorin. Esophageal resection was performed followed by AD therapy. RESULTS: Thirty-three patients initiated NAD therapy; 10 experienced grade 3 and 4 toxicities, which included leucopenia, fatigue, nausea, diarrhea and stomatitis. Additionally, 16 patients experienced grade 1 and 2 hematologic and non-hematologic toxicities. Fifteen patients were down-staged, of whom five were T2, seven were T1, and three had nodal disease with no evidence of residual cancer in the esophageal bed. Fifteen patients remained T3, and two showed progressive disease. Thirty-two patients proceeded to surgery and 30 were resected. Although all resected patients were eligible for AD therapy, 15 did not receive it either because of patient refusal or surgeon recommendation. Fifteen patients received AD therapy: nine who had remained T3 and six who had down-staged. Three patients experienced grade 3 and 4 toxicities similar to those in NAD therapy. Six patients had grade 1 and 2 toxicities. Kaplan-Meier estimates of overall survival at 1, 3 and 5 years were 73% (95% CI: 58-88%), 52% (95% CI: 34-69%) and 29% (95% CI: 13-45%), respectively. Median survival was 42 months. CONCLUSION: Deletion of RT may safely allow for more aggressive chemotherapy and increase chances of survival. The results need to be confirmed in a randomized phase II or larger phase III trial.

Arsenic trioxide/ascorbic acid therapy in patients with refractory metastatic colorectal carcinoma: a clinical experience.

Arsenic trioxide (As2O3) has demonstrated effectiveness in treating acute promyelocytic leukemia (APL). Therefore the FDA has approved it to treat APL. In patients with refractory metastatic colorectal carcinoma (CRC), we assessed the efficacy and toxicity of As2O3/AA (ascorbic acid) as the outcome of this trial. Five patients with refractory metastatic CRC who failed all previous standard chemotherapy were enrolled in this study. They were treated with 0.25 mg/kg body weight/day As2O3 and 1000 mg/day of ascorbic acid for 5 days a week for 5 weeks. Each treatment cycle extended for 7 weeks with 5 weeks of treatment and 2 weeks of rest. All the patients developed moderate to severe toxic side effects to arsenic trioxide/AA therapy and therefore the study was discontinued. No CR (complete remission) or PR (partial remission) was observed. CT scans demonstrated stable or progressive disease. Three of the five patients died within 2 to 5 months after cessation of the therapy. None of the deaths could be related to this clinical trial. Two years of follow-up study showed that two patients were alive with stable disease. Under the current treatment regimen all patients developed moderate to severe side effects with no clinically measurable activity. As an alternate, efforts may be made to reduce the dose and arsenic trioxide may be combined with other standard regimen in reversing the chemo resistance.

Endoscopic ultrasound restaging after neoadjuvant chemotherapy in esophageal cancer.

BACKGROUND: The role of endoscopic ultrasound (EUS) to evaluate treatment response postneoadjuvant therapy for restaging esophageal cancer prior to surgical resection is uncertain. Accuracy of EUS is lower but potential to predict response to chemoradiation indicates that EUS may be helpful prior to surgery. OBJECTIVE: To determine staging accuracy of EUS after neoadjuvant chemotherapy, predictors of tumor response, and survival in locally advanced esophageal cancer. METHODS: Single-center retrospective evaluation of patients with locally advanced esophageal cancer on a prospective chemotherapy study. Patients who underwent EUS without FNA pre- and postchemotherapy were included. RESULTS: A total of 49 patients (43 men and 6 women) were evaluated with EUS pre- and postneoadjuvant chemotherapy. Forty-seven patients had tumor localized at the GE junction and two had mid-esophageal lesions. The median survival time was 53 months. Tumor and nodal staging accuracy postchemotherapy were 60% (27 of 45). T-stage accuracy postchemotherapy was superior in patients without a response to chemotherapy (95.7%vs 26.1%, p<0.0001). More than 50% in reduction of tumor thickness postchemotherapy was associated with tumor downstage and better survival. N0 disease on final pathology was the best predictor of improved survival. CONCLUSION: Accuracy of EUS postchemotherapy is lower than initial staging accuracy; therefore the ability to predict downstaging based on EUS is marginal. Pathology N1 disease postchemotherapy is the best predictor of survival. EUS staging postneoadjuvant chemotherapy should focus on improving nodal staging accuracy with FNA.

A phase II trial of FUdR in patients with advanced pancreatic cancer.

PURPOSE: This phase II study was conducted to assess the efficacy of fluorodeoxyuridine (FUdR) in patients with metastatic, advanced pancreatic cancer who had no previous chemotherapy. PATIENTS AND METHODS: Twenty patients were enrolled in this single institution trial. The primary endpoint of this study was the assessment of overall survivorship. The secondary endpoints were to estimate the time to tumor progression and the assessment of toxicity in this cohort of patients. Treatment consisted of FUdR 150 mg/kg dissolved in 500 cc normal saline intravenous infusion over 24 h. Eight weeks of treatment constituted one course of chemotherapy. Tumor measurements were conducted at 8-weekly intervals. RESULTS: Four patients achieved partial response and 16 patients had stable disease. Median survival of patients treated with FUdR was 11.6 months with a range of 3-16 months. Median progression-free survival was 6 months. Overall, chemotherapy was well tolerated with low incidence of grade 3 or 4 toxicity. CONCLUSIONS: Systemic chemotherapy with high dose FUdR administered on a weekly schedule has led to encouraging survival outcomes and improved quality of life as compared to previous phase II single agent chemotherapeutic trials.