Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen)

Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500mgm-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60mgm_1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following ‘megatherapy’ given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2, 000 Hz in 37% of children but at or below 2, 000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate

Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values

Advances in neonatal cardiac imaging permit a more comprehensive assessment of myocardial performance in neonates that could not be previously obtained with conventional imaging. Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in neonates. Cardiac strain is a measure of tissue deformation and strain rate is the rate at which deformation occurs. These measurements are obtained in neonates using tissue Doppler imaging (TDI) or two-dimensional speckle tracking echocardiography (STE). There is an expanding body of literature describing longitudinal reference ranges and maturational patterns of strain values in term and preterm infants. A thorough understanding of deformation principles, the technical aspects, and clinical applicability is a prerequisite for its routine clinical use in neonates. This review explains the fundamental concepts of deformation imaging in the term and preterm population, describes in a comparative manner the two major deformation imaging methods, provides a practical guide to the acquisition and interpretation of data, and discusses their recognized and developing clinical applications in neonates

Introduction to neonatologist-performed echocardiography

Cardiac ultrasound techniques are increasingly used in the neonatal intensive care unit to guide cardiorespiratory care of the sick newborn. This is the first in a series of eight review articles discussing the current status of "neonatologist-performed echocardiography" (NPE). The aim of this introductory review is to discuss four key elements of NPE. Indications for scanning are summarized to give the neonatologist with echocardiography skills a clear scope of practice. The fundamental physics of ultrasound are explained to allow for image optimization and avoid erroneous conclusions from artifacts. To ensure patient safety during echocardiography recommendations are given to prevent cardiorespiratory instability, hypothermia, infection, and skin lesions. A structured approach to echocardiography, with the same standard views acquired in the same sequence at each scan, is suggested in order to ensure that the neonatologist confirms normal structural anatomy or acquires the necessary images for a pediatric cardiologist to do so when reviewing the scan

The role of Neonatologist Performed Echocardiography in the assessment and management of neonatal shock

One of the major challenges of neonatal intensive care is the early detection and management of circulatory failure. Routine clinical assessment of the hemodynamic status of newborn infants is subjective and inaccurate, emphasizing the need for objective monitoring tools. An overview will be provided about the use of neonatologist-performed echocardiography (NPE) to assess cardiovascular compromise and guide hemodynamic management. Different techniques of central blood flow measurement, such as left and right ventricular output, superior vena cava flow, and descending aortic flow are reviewed focusing on methodology, validation, and available reference values. Recommendations are provided for individualized hemodynamic management guided by NPE

Application of NPE in the assessment of a patent ductus arteriosus

In many preterm infants, the ductus arteriosus remains patent beyond the first few days of life. This prolonged patency is associated with numerous adverse outcomes, but the extent to which these adverse outcomes are attributable to the hemodynamic consequences of ductal patency, if at all, has not been established. Different treatment strategies have failed to improve short-term outcomes, with a paucity of data on the correct diagnostic and pathophysiological assessment of the patent ductus arteriosus (PDA) in association with long-term outcomes. Echocardiography is the selected method of choice for detecting a PDA, assessing the impact on the preterm circulation and monitoring treatment response. PDA in a preterm infant can result in pulmonary overcirculation and systemic hypoperfusion, Therefore, echocardiographic assessment should include evaluation of PDA characteristics, indices of pulmonary overcirculation with left heart loading conditions, and indices of systemic hypoperfusion. In this review, we provide an evidence-based overview of the current and emerging ultrasound measurements available to identify and monitor a PDA in the preterm infant. We offer indications and limitations for using Neonatologist Performed Echocardiography to optimize the management of a neonate with a PDA

Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values

Neonatologists can use echocardiography for real-time assessment of the hemodynamic state of neonates to support clinical decision-making. There is a large body of evidence showing the shortcomings of conventional echocardiographic indices in neonates. Newer imaging modalities have evolved. Tissue Doppler imaging is a new technique that can provide measurements of myocardial movement and timing of myocardial events and may overcome some of the shortcomings of conventional techniques. The high time resolution and its ability to assess left and right cardiac function make tissue Doppler a favorable technique for assessing heart function in neonates. The aim of this review is to provide an up-to-date overview of tissue Doppler techniques for the assessment of cardiac function in the neonatal context, with focus on measurements from the atrioventricular (AV) plane. We discuss basic concepts, protocol for assessment, feasibility, and limitations, and we report reference values and give examples of its use in neonates