Search

The observation that neuroectodermal differentiation imparts a worse prognosis to the Ewing family of tumors has been suggested by some studies and refuted by others. To assess whether the diagnosis of Ewing's sarcoma versus peripheral primitive neuroectodermal tumor (PNET) affects prognosis, we analyzed tumors from 63 analogously treated pediatric and young adult patients from the National Cancer Institute and St Jude Children's Research Hospital and retrospectively compared the results with clinical outcomes. The tumors were assessed using standard light microscopy and immunohistochemical stains for neuron-specific enolase, CD57, S100 protein, neurofilament protein, and synaptophysin with or without antigen retrieval. Ultrastructural evaluation was also performed in 39 tumors. Classification was performed using Kiel criteria as well as a modified classification. Kaplan-Meier analyses, with Mantel-Haenzel evaluation of the significance of the differences, were performed separately for localized or metastatic tumors. Using the Kiel classification on a subset of 60 cases, 39 tumors qualified as PNET and 21 as Ewing's sarcoma. Using the modified classification on a subset of 61 cases, 14 were classified as PNET, 21 as atypical Ewing's sarcoma, and 26 as Ewing's sarcoma. The addition of electron microscopy to the diagnostic armamentarium significantly increased the likelihood of identifying PNET. No significant differences in event-free or overall survival were seen using either the modified or Kiel classification, regardless of the ancillary diagnostic techniques employed. In this exploratory analysis, neuroectodermal differentiation did not play a role in clinical outcome. Confirmation of this finding will require a larger, separate study of similarly treated patients, and it may not apply to older patients.

Purpose: There are a variety of solid tumors in which alternative chromosomal translocations generate related fusion products. In alveolar rhabdomyosarcoma and synovial sarcoma, these variant fusions have been found to have major clinical significance. We investigated whether the two alternative gene fusion products, EWS-FLI1 and EWS-ERG, define different clinical subsets within the Ewing's sarcoma family of tumors., Patients and Methods: We selected 30 cases of Ewing's sarcoma with the EWS-ERG gene fusion and 106 cases with the EWS-FLI1 fusion. Clinical data were obtained for each case and compared with the molecular diagnostic findings., Results: There were no significant clinical differences observed between the two groups in age of diagnosis, sex, metastasis at diagnosis, primary site, event-free survival, or overall survival., Conclusion: Differences in the C-terminal partner in the Ewing's sarcoma family gene fusions are not associated with significant phenotypic differences.

Anthracyclines have major activity against a broad range of childhood cancers. Concern over the risk of long-term cardiotoxicity associated with their use has called into question the role of these agents in the frontline treatment of many patients. Dexrazoxane was developed as a specific cardioprotectant "antidote" which can prevent anthracycline cardiotoxicity without inhibiting its antitumor effect. To date, four clinical trials of dexrazoxane have been conducted in pediatric cancer patients (primarily with sarcomas). The two largest series, conducted at the National Cancer Institute Pediatric Branch, demonstrated significant short-term cardioprotection with no evidence of interference with antitumor activity. Additional clinical trials are ongoing, or planned to open shortly, to better evaluate the role of dexrazoxane in the treatment of childhood cancer. These studies, being conducted on larger numbers of patients with better prospects for cure, are expected to definitviely answer the outstanding questions of whether preventing short-term, subclinical cardiotoxicity will translate into long-term cardioprotection, and whether the use of dexrazoxane interferes with the anti-tumor efficacy of doxorubicin-containing regimens.

Background: Patients with chronic obstructive pulmonary disease are usually excluded from intravenous dipyridamole thallium-201 testing. We developed a nurse-administered protocol to screen and pretreat patients so they could be safely tested., Methods and Results: We prospectively screened patients referred for intravenous dipyridamole thallium testing and retrospectively reviewed a comparison group of patients who had undergone intravenous dipyridamole testing before our bronchospasm protocol. We studied 492 consecutive patients referred for intravenous dipyridamole thallium testing, separating those with complete data (n = 451) into two groups: group A (n = 72), patients assessed to be at risk for intravenous dipyridamole-induced bronchospasm who received our bronchospasm treatment protocol; and group B (n = 379), patients assessed to be free of risk, who did not receive our bronchospasm protocol. Group C (n = 89) was a retrospective comparison group of patients who had undergone intravenous dipyridamole testing before initiation of the protocol. Patients were considered at risk for an adverse event if any of the following were present: peak flow < or =400 ml at the time of the test (spirometry by nurse) that increased to >400 ml after bronchodilator treatment, wheezing audible with stethoscope, history of chronic obstructive pulmonary disease or asthma or dyspnea on exertion at less than four blocks, or resting respiratory rate >18 breaths/min. The test was considered contraindicated if resting oxygen saturation was <85%, respiratory rate < or =36 breaths/min, or peak flow measured by peak flowmeter <400 ml after bronchodilator inhalant (albuterol or metaproterenol sulfate by spacer) at a dose of up to six puffs. One minute after injections of thallium-201, patients at risk were given 50 mg aminophylline by slow intravenous injection. We looked for major and minor adverse effects and divided them into three categories: (1) minor events (transient headache, abdominal discomfort, or nausea), wheezing (audible by stethoscope but without marked respiratory distress), (2) marked events (severe bronchospasm or severe ischemia defined as wheezing audible with or without stethoscope, respiratory rate >20 breaths/min or increased by 10 from pretest evaluation, oxygen desaturation to <90%, hypoventilation [reduced respiratory rate with decreased mental status], respiratory arrest, chest pain, horizontal ST-segment depression > or =1 mm on the electrocardiogram in any lead, symptomatic hypotension), or (3) other intravenous dipyridamole-induced side effects (persistent headache, dizziness, flushing, nausea, dyspnea, and ischemic chest pain) or anginal equivalent. The protocol properly identified patients with impaired pulmonary function. There was no difference in the frequency of adverse marked events among groups A, B, or C (1 % vs 4% vs 2%, p = 0.25). Patients in group A had more minor side effects than those in group B (53% vs 35%, p = 0.004). Specifically, patients in group A were more likely to wheeze (39% vs 1 %, p = <0.001), but wheezing in group A was self-limited or responded to treatment as described in the protocol. The prevalence of positive thallium-201 scans in group A (44%) compared with group C (49%) was not different (p = 0.15)., Conclusions: A nurse-administered risk assessment and pretreatment protocol (1) properly identified patients with impaired pulmonary function, (2) permitted completion of intravenous dipyridamole testing in patients at risk for bronchospasm without an increased incidence of marked adverse events, and (3) did not appear to influence the interpretation of the thallium test.

Background: Non-Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization)., Methods: We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non-Q-wave infarction. Death or nonfatal infarction made up the combined primary end point., Results: During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P= 0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01)., Conclusions: Most patients with non-Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.

Congenital diaphragmatic hernia (CDH) may be associated with other anomalies, most frequently cardiovascular in nature. Despite fetal echocardiography, diagnosis of an accompanying cardiac malformation often is not made until after birth and sometimes not until after extracorporeal membrane oxygenation (ECMO) has been instituted. Aortic coarctation associated with CDH may occur as an isolated, surgically correctable malformation or it may be a component of the usually fatal left heart "hypoplasia" or "smallness" syndrome. The authors present two cases of aortic coarctation associated with CDH requiring ECMO that illustrate the management challenges of these coincident diagnosis. In one case, the accompanying coarctation was suspected and required precannulation angiography for confirmation, whereas in the other case, the diagnosis of coarctation was not made until after ECMO cannulation. Depending on its anatomic location and severity, an aortic coarctation associated with life-threatening CDH may limit the physiological efficacy of venoarterial ECMO. Furthermore, arterial cannulation for extracorporeal support requires that flow through the remaining carotid artery be maintained during aortic reconstruction, which may prove difficult for lesions best treated by subclavian flap angioplasty. When the diagnosis of coincident aortic coarctation and CDH is suspected or proven before institution of extracorporeal support, serious consideration should be given to venovenous bypass, because this may provide better postductal oxygenation and facilitate aortic repair with the option of left carotid artery inflow occlusion.

The 10-year survival rate of patients with systemic lupus erythematosus (SLE) currently is more than 85|X%; the greater longevity permits late complications to emerge. Recent studies have shown an increased incidence of coronary artery disease (CAD), frequently in young adults. CAD currently is among the most common causes of death in patients with SLE who survive longer than 5 years. Multiple risk factors, some specific to SLE, are implicated in premature development of CAD. These include coronary artery vasculitis, hypertension and hyperlipidemia, corticosteroid therapy, and antiphospholipid antibodies, which may result in coronary thrombotic events. Therefore, risk factors for CAD should be actively sought as part of routine care of patients with SLE, and appropriate modification strategies, including medications if necessary, should be employed. Noninvasive cardiac tests should be used early in the evaluation of any symptoms consistent with myocardial ischemia, heart failure, or cardiac arrhythmias.

Rapid recovery of CD4+ T cells after intensive chemotherapy is limited by an age-dependent decline in thymopoiesis. Here we sought to determine whether similar limitations exist for CD8+ T-cell regeneration. After intensive chemotherapy, CD8+ T cells had a faster effective doubling time than CD4+ T cells (median, 12.6 v 28.2 days, P < .05). Accordingly, at 3 months posttherapy, mean CD8+ T-cell number had returned to baseline, whereas mean CD4+ T-cell number was only 35% of pretherapy values (P < .05). These differences were primarily due to very rapid expansion of CD8+CD57+ and CD8+CD28- subsets. At 3 months posttherapy, there was no relationship between age and CD8+ T-cell number (R = -.02), whereas CD4+ T-cell number was inversely related to age (R = -.66) and there were no discernible differences in CD8+ recovery among patients with or without thymic enlargement, whereas CD4+ recovery was enhanced in patients with thymic enlargement after chemotherapy (P < .01). Therefore thymic-independent pathways of T-cell regeneration appear to rapidly regenerate substantial numbers of CD8+, but not CD4+ T cells, resulting in prolonged T-cell subset imbalance after T-cell depletion. These inherent distinctions between CD4+ v CD8+ T-cell regeneration may have significant implications for immunotherapeutic strategies undertaken to eradicate minimal residual neoplastic disease after cytoreductive chemotherapy.

Purpose: This late effects study was designed to determine if survivors of Ewing's sarcoma family tumors (ESFT) had adverse outcomes in employment, marital status, fertility, and functional status when compared to sibling controls., Subjects and Methods: Eighty-nine survivors (case subjects) of ESFT treated at the National Cancer Institute between 1965 and 1992 and 97 sibling controls completed a questionnaire probing aspects of quality of life. The answers from case subjects were compared to pooled and matched sibling controls for all key variables. Odds ratios (OR) and p values from pooled analyses are presented., Results: Although case subjects and controls did not differ in educational achievement, case subjects were less likely to be employed full-time (OR 0.4, p < 0.01), to be married (OR 0.2, p < 0.01), and to have children (OR 0.3, p < 0.01). Their most common treatment-related difficulties included permanent hair and skin changes (43%), lung problems (18%), neurologic problems (14%), visual difficulties (10%), second malignancy (7%), and amputation (5%). Functional status, measured by Karnofsky performance scale, was also adversely affected in case subjects. Case subjects did not differ from sibling controls in health care insurance status or in utilization of health services., Conclusions: Important aspects of life such as employment, marital status, fertility, and functional status are affected in survivors of ESFT. More studies are needed to better define the health status of adult survivors of pediatric cancer and the impact of cancer in adolescence on psychosocial development.

We present an 8-year-old African-American boy with medulloblastoma and nevoid basal cell carcinoma syndrome (NBCCS) who exhibited the radiosensitive response of basal cell carcinoma (BCC) formation in the area irradiated for medulloblastoma. Such a response is well-documented in Caucasian NBCCS patients with medulloblastoma. The propositus was diagnosed with medulloblastoma at the age of 2 years and underwent surgery, chemotherapy, and craniospinal irradiation. At the age of 6 years, he was diagnosed with NBCCS following his presentation with a large odontogenic keratocyst of the mandible, pits of the palms and soles and numerous BCCs in the area of the back and neck that had been irradiated previously for medulloblastoma. Examination of other relatives showed that the propositus' mother also had NBCCS but was more mildly affected; in particular, she had no BCCs. This case illustrates complex gene-environment interaction, in that increased skin pigmentation in African-Americans is presumably protective against ultraviolet, but not ionizing, radiation. This case and other similar cases in the literature show the importance of considering NBCCS in the differential diagnosis of any patient who presents with a medulloblastoma, especially before the age of 5 years, and of examining other close relatives for signs of NBCCS to determine the patient's at-risk status. Finally, for individuals who are radiosensitive, protocols that utilize chemotherapy in lieu of radiotherapy should be considered.

Background: This study was conducted to determine the feasibility of, and improve outcome by, incorporating ifosfamide and etoposide (IE) into the therapy of newly diagnosed patients with Ewing's sarcoma family of tumors of bone and soft tissue., Methods: Fifty-four newly diagnosed patients received 7 cycles of vincristine, doxorubicin, and cyclophosphamide (VAdriaC) and 11 cycles of IE. Radiation therapy after the fifth chemotherapy cycle was the primary approach to local control., Results: Actuarial 5-year event-free survival (EFS) and overall survival rates were 42% and 45%, respectively, with a median duration of potential follow-up of 6.8 years. EFS was significantly better for patients with localized tumors than for those with metastatic lesions (64% v. 13%, P < 0.0001). Actuarial local progression-free survival at 5 years was 74%, and did not correlate with primary tumor size or site, histologic subtype, or the presence of metastases. Febrile neutropenia developed after 49% of cycles, and clinical or sub-clinical cardiac dysfunction was common (7% and 40% respectively). There were four toxic deaths and one case of secondary myelodysplastic syndrome., Conclusions: Despite substantial toxicity, the integration of IE into the front-line, VAdriaC-based therapy of patients with Ewing's sarcoma family of tumors is feasible and appeared to significantly improve the outcome for patients with high risk localized tumors, but had no impact on the poor prognosis of patients with metastatic tumors. Local control can be achieved in the vast majority of patients using radiotherapy exclusively, even among patients with bulky, central axis tumors. Longer follow-up is needed to evaluate the late effects of this intensive therapy.

Preoperative malnutrition increases the morbidity rate and length of hospitalization for various types of surgical patients. However, among patients who undergo elective total hip replacement, it is unclear how preoperative nutritional data can be used to detect a high risk subgroup. The purpose of this study was to identify preoperative nutritional factors that could be used to define a subgroup of patients who have undergone elective total hip replacement who are at high risk for poor post-operative outcome. Preoperative nutritional factors were evaluated in 89 consecutive patients who underwent elective total hip replacement. An inverse relationship was found between serum albumin and length of stay. Patients with an albumin level less than 3.9 were twice as likely to require prolonged hospitalization ( > 15 days) when compared with those in whom the albumin level was 3.9 or greater. Complications were related to the preoperative orthopaedic diagnosis of avascular necrosis of the hip. A subgroup of the patients undergoing elective total hip replacement who are at risk for prolonged recovery can be identified preoperatively by using a serum albumin level of less than 3.9 g/dL. The traditional normal range for albumin may be inappropriate for these patients.

In an effort to understand the effect of cancer diagnosis and treatment in children and adolescents, and to identify issues that should be addressed with newly diagnosed patients, 85 patients with Ewing's sarcoma family tumors (ESFT) were interviewed about their experience of having cancer. This represents 90% of all eligible patients who survived at least 3 years since their diagnosis and who were treated for ESFT at the National Cancer Institute (NCI) from 1965-1993. The mean age of patients at the time of diagnosis was 15.8 +/- 5.3 years, and mean time since diagnosis was 13.6 +/- 6.4 years. Patients from this cohort had a disease usually related to poor outcome. Patients answered five open-ended written questions. Negative experiences that they described included transient and permanent discomfort and disabilities related to cancer; disruption of life or relationships; and emotional aspects of cancer diagnosis or treatment. Positive aspects of having cancer included changed attitudes about self and life, improved relationships with others, or better job performance. Advice for newly diagnosed patients most often dealt with the emotional aspects of cancer. The importance of patient-to-patient support was frequently described. Overall, having cancer was not an entirely negative experience, and it may result in introspection and improved relationships with others.

Background: The Cincinnati (Ohio) Department of Veterans Affairs Medical Center Lipid Clinic was established as a collaborative practice to treat patients with substantially elevated serum cholesterol levels referred from the General Internal Medicine Clinic. The Lipid Clinic team (led by a clinical nurse), included a clinical pharmacist, nurse practitioner, dietitian, and clinical psychologist. A consultant cardiologist reviewed all laboratory tests and confirmed therapeutic decisions at a weekly preclinic meeting., Objective: To compare the success of a limited term of treatment in the Lipid Clinic with that of standard physician-based care in the General Internal Medicine Clinic in achieving the goals recommended by the National Cholesterol Education Program 1 for low-density lipoprotein cholesterol., Methods: A convenience sample of age-matched patients with total cholesterol levels greater than 6.85 mmol/L (265 mg/dL) was selected from each clinic (Lipid Clinic, n = 60; General Internal Medicine Clinic, n = 60). Fasting lipid profiles were drawn in the free-living state and in the sitting position, and matched by month. Treatment of patients in the Lipid Clinic group consisted of evaluation and treatment of secondary causes of hyperlipidemia, goal setting, and treatment according to the National Cholesterol Education Program I algorithm. Counseling and education were individualized. Outcomes were determined after four visits (12 and 18 months for the Lipid Clinic and General Internal Medicine Clinic groups, respectively). Patients in the two groups had comparable risk factors, including presence of coronary heart disease., Results: After four clinic visits, patients in the Lipid Clinic group were four times more likely to reach a National Cholesterol Education Program I goal of a low-density lipoprotein cholesterol level less than 3.36 mmol/L (130 mg/dL) than were comparable patients in the General Internal Medicine Clinic group (relative risk, 4.1; 95% confidence interval, 1.4 to 12.7; P < .001)., Conclusion: These results support multidisciplinary, goal-oriented collaborative practice as an efficacious model of preventive medicine and health care provision.

We reviewed our experience of pediatric metastasectomy to define (1) morbidity/mortality in this population and (2) any preoperative or intraoperative prognostic predictors of survival. One hundred fifty-two patients with median age 19 years (range, 5 to 33 years) had 258 thoracic explorations (Ewing's sarcoma, 28; rhabdomyosarcoma, 6; nonrhabdomyosarcoma soft tissue sarcoma, 42; and osteosarcoma, 76). Resections were accomplished by 218 wedge resections, 19 anatomic resections, 14 wedge and anatomic resections, 4 wedge and chest wall resections, and 3 wedge resections/other procedures. An initial complete resection was accomplished in 121/152 patients (80%). With a median potential follow-up of 10.6 years, median survival from initial thoracotomy is 2.2 years. By the Cox proportional hazards model, three or more positive nodules (p = 0.021), histology other than osteosarcoma (p = 0.0054), and incomplete resection (p < 0.0001) were unfavorable prognostic factors for survival. Two or more positive nodules (p = 0.0049), left location (p = 0.0031), age 14 years or greater at diagnosis (p = 0.0052), or rhabdomyosarcoma (p = 0.0066) predicted shorter pulmonary progression-free survivals after resection. Nonrhabdomyosarcoma pediatric metastasectomy can yield selected long-term survival. Morbidity/mortality is low, and a complete resection, if possible, is paramount. Prognostic factors can be defined that can be used to define the limits of this therapy to the patient and family.

Objective: To determine the prevalence and effect of sleep-disordered breathing in ambulatory patients with stable, optimally treated congestive heart failure., Design: A prospective, longitudinal study., Setting: Referral sleep laboratory of a Department of Veterans Affairs medical center., Patients: 42 of the 48 eligible patients with stable congestive heart failure and left ventricular systolic dysfunction (left ventricular ejection fraction < or = 45%)., Measurements: After an adaptation night, polysomnography and Holter monitoring were done in the sleep laboratory. Arterial blood gases and pH were measured, and cardiac radionuclide ventriculography and pulmonary, renal, and thyroid function tests were done., Results: Patients were divided into two groups. Group I (n = 23) had an hourly rate of apnea and hypopnea (apnea-hypopnea index) of 20 episodes per hour or less; group II (n = 19 [45%; CI, 30% to 60%]) had an index of more than 20 episodes per hour. In group II, the index varied from 26.5 to 82.2 episodes per hour (mean +/- SD, 44 +/- 13 episodes per hour; CI, 38 to 51 episodes per hour). Group II had significantly more arousals (24 +/- 12 compared with 3 +/- 3 in group I) that were directly attributable to episodes of apnea and hypopnea, longer periods of time with an arterial oxyhemoglobin saturation of less than 90% (23% +/- 24% of total sleep time compared with 2% +/- 4%), lower arterial oxyhemoglobin saturation during sleep (74% +/- 13% compared with 87% +/- 4%), lower left ventricular ejection fraction (22% +/- 9% compared with 30% +/- 10%), and a significantly increased number of episodes of nocturnal ventricular arrhythmias. Multiple regression analyses showed that left ventricular systolic dysfunction was an independent risk factor for sleep apnea in patients with congestive heart failure., Conclusions: The prevalence of severe occult sleep-disordered breathing is high in ambulatory patients with stable, optimally treated chronic congestive heart failure. The breathing episodes are associated with severe nocturnal arterial blood oxyhemoglobin desaturation and excessive arousals. Severe untreated sleep-disordered breathing may adversely affect left ventricular function, resulting in a vicious cycle that could contribute to death in patients with congestive heart failure. Prospective, longitudinal studies on survival are needed.

We have characterized the coronary vascular reserve, left ventricular function and inotropic response in dogs with chronic heart failure consequent to intracoronary embolization (EMB) with 50 microns spheres. We conducted studies 12-39 months after embolization and contrasted the findings with normal (CON) dogs. Acute embolization produced sustained LV volume enlargement and increased wall thickness, reduction of LV ejection fraction and elevated end-diastolic pressures; resting catecholamine levels were also increased. Responses to phenylephrine, nitroprusside, and dobutamine were identical in CON and EMB and coronary vasodilator reserve was reduced despite larger coronary vascular volume. Analysis by light microscopy showed a diffuse focal and interstitial fibrosis distributed uniformly from endocardium to epicardium associated with 14% loss of myocytes. This created a functional separation of myocardial muscle bundles and a disruption of the syncytial nature of the heart. Electron microscopy of the areas of fibrosis revealed myocytes in states ranging from normal appearing, to ghosts with evidence of cytolysis and loss of the sarcolemma. This model of chronic congestive heart failure with LV systolic dysfunction and elevated LV diastolic pressures shares a number of features with the syndrome in humans.

The incidence of nephrotoxicity occurring with the nonionic contrast agent, iohexol, and the ionic contrast agent, meglumine/sodium diatrizoate, was compared in 1196 patients undergoing cardiac angiography in a prospective, randomized, double-blind multicenter trial. Patients were stratified into four groups: renal insufficiency (RI), diabetes mellitus (DM) both absent (N = 364); RI absent, DM present (N = 318); RI present, DM absent (N = 298); and RI and DM both present (N = 216). Serum creatinine levels were measured at -18 to 24, 0, and 24, 48, and 72 hours following contrast administration. Prophylactic hydration was administered pre- and post-angiography. Acute nephrotoxicity (increase in serum creatinine of > or = 1 mg/dl 48 to 72 hours post-contrast) was observed in 42 (7%) patients receiving diatrizoate compared to 19 (3%) patients receiving iohexol, P < 0.002. Differences in nephrotoxicity between the two contrast groups were confined to patients with RI alone or combined with DM. In a multivariate analysis, baseline serum creatinine, male gender, DM, volume of contrast agent, and RI were independently related to the risk of nephrotoxicity. Patients with RI receiving diatrizoate were 3.3 times as likely to develop acute nephrotoxicity compared to those receiving iohexol. Clinically severe adverse renal events were uncommon (N = 15) and did not differ in incidence between contrast groups (iohexol N = 6; diatrizoate N = 9). In conclusion, in patients undergoing cardiac angiography, only those with pre-existing RI alone or combined with DM are at higher risk for acute contrast nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance (MR) imaging techniques have evolved sufficiently to produce clinically relevant studies that depict the anatomy and physiology of the heart. Applications to congenital cardiac disease in adult patients are numerous. MR imaging is particularly useful for noninvasive evaluation of the aorta in patients with aortic arch anomalies and coarctations and to study the results of palliative and corrective surgery for transposition of the great arteries and for reconstructive procedures that restore sufficient pulmonary blood flow. MR imaging is superior to transthoracic echocardiography in defining the anatomy of the central pulmonary arteries. Recent technological advances permit motion studies acquired during a single breath-hold and can be used to accurately measure stroke volume, ejection fraction, regional wall motion, and wall thickening from both ventricles. Functional parameters, such as the velocity and volume of blood flow in vessels, valve gradients, regurgitant flow, shunt flow, and pulmonary artery blood flow into each lung are readily performed. This review article documents the value of MR imaging in adult patients with congenital disorders of the heart, pulmonary arteries, and aorta, and includes illustrations of typical examples.

Palliative and corrective operations for the treatment of cyanotic congenital heart disease frequently involve or potentially influence the size of the pulmonary arteries. Echocardiography and magnetic resonance imaging (MRI) are two noninvasive imaging techniques currently used to assess morphologic abnormalities of the pulmonary arteries. The purpose of this study was to evaluate the role of MRI in comparison with echocardiography for defining morphologic changes of the pulmonary arteries after congenital heart surgery. The MRI scans and echocardiograms of 33 patients with surgery involving or affecting the pulmonary arteries were compared. The pulmonary outflow tract, pulmonary confluence, right and left pulmonary arteries, and surgical shunts were separately evaluated. Cineangiography and surgical reports were used to confirm findings. MRI and echocardiography were equivalent for demonstrating abnormalities of the right ventricular outflow tract, main pulmonary artery, and a variety of pulmonary shunts. MRI was superior to echocardiography in demonstrating abnormalities of the right and left pulmonary arterial branches (p < 0.001). MRI is effective for monitoring pulmonary arterial status after surgery and is superior to echocardiography for the evaluation of the right and left pulmonary arteries.

Background: Previous studies of the genetic epidemiology of Ewing's sarcoma have shown neither an increased incidence nor a distinct pattern of cancers in family members of Ewing's sarcoma patients., Purpose: Because of a new biologic and cytogenetic classification of Ewing's sarcoma family of tumors, we wanted to reinvestigate the incidence and distribution of cancers in relatives of probands with Ewing's sarcoma family of tumors., Methods: Patients treated at the Pediatric Branch and the Radiation Oncology Branch of the National Cancer Institute between 1965 and December 1992, or their next of kin, were asked to complete a questionnaire on the history of cancer in all first- and second-degree relatives. The incidence of cancer in family members was compared with Connecticut Tumor Registry rates specific for sex, age, and 5-year calendar-year intervals. Observed/expected (O/E) ratios, 95% confidence intervals (CIs), and tests of homogeneity were calculated., Results: Four thousand six hundred seventy-eight family members with 196,640 person-years at risk entered the analysis. Overall, there was no increased risk of cancer (observed 472; O/E = 0.9; 95% CI = 0.8-1.0). However, several tumor types were found in significant excess. These tumors included stomach cancer (observed 34; O/E = 2.0; 95% CI = 1.4-2.8), melanoma (observed 23; O/E = 1.9; 95% CI = 1.2-2.8), brain tumor (observed 18; O/E = 1.9; 95% CI = 1.1-3.0), and bone cancer (observed 7; O/E = 4.2; 95% CI = 1.7-8.6). Risks of these cancers were higher among maternal than paternal relatives, but these differences were not statistically significant. There was a significant deficit of bladder cancer (observed 5; O/E = 0.2; 95% CI = 0.1-0.5) and rectal cancer (observed 0; O/E = 0.0; 95% CI = 0.0-0.1). Second-degree relatives had a significant cancer deficit (observed 389; O/E = 0.9; 95% CI = 0.8-0.95). This deficit was accounted for by the observed deficit of bladder and rectal cancer and is probably related to under-reporting or misclassification of cancer in second-degree relatives. Family members of 10 probands with second malignancies did not have an increased risk of all cancers (observed 20; O/E = 1.2; 95% CI = 0.7-1.8) but had an increased risk of both melanoma (observed 3; O/E = 7.3; 95% CI = 1.5-21.0) and breast cancer (observed 8; O/E = 3.2; 95% CI = 1.4-6.3)., Conclusion: Finding an increased risk of neuroectodermal tumors and stomach cancer in families of patients with Ewing's sarcoma family of tumors suggests that these tumors might share a common etiology. Further studies should try to confirm this hypothesis and to examine if genetic factors may have a role in these families by assessing the mode of inheritance and examining families with multiple affected members.

Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.

Purpose: The records of 28 patients with sarcomas of the hand and foot treated at the National Cancer Institute (NCI) between 1977 and 1992 were reviewed to assess local control and functional results., Methods and Materials: Histologic types included 15 cases of the Ewing's sarcoma family of tumors, 7 cases of alveolar rhabdomyosarcoma, and 6 cases of nonrhabdomyosarcoma soft tissue sarcomas. Median age of all patients was 18 years (range 4-61), with a median potential follow-up of 114 months following diagnosis. Surgery varied from incisional biopsies for Ewing's Sarcoma and rhabdomyosarcoma lesions to complete excision when possible for nonrhabdomyosarcoma soft tissue sarcoma lesions. Amputation was not primarily performed, except in two patients who underwent ray resections of hand lesions (patients 13 and 24). Radiotherapy generally consisted of 50 Gy/25 fractions (fx)/5 weeks for Ewing's Sarcoma, 54 Gy/30 fx/6 weeks for rhabdomyosarcoma, and 63 Gy/35 fx/7 weeks for nonrhabdomyosarcoma soft tissue sarcomas. Chemotherapy was administered on various NCI protocols., Results: Actuarial local control for Ewing's Sarcoma was 84% at 5 and 10 years. All but one survivor are capable of hand/foot function for routine activities without orthotic requirements. Five of six patients (83%) who died of metastatic disease had functional distal extremities. Actuarial local control for rhabdomyosarcomas was 100%, with equivalent function. No patient developed a second malignancy in the treatment field., Conclusions: Although equivalent local control may be achieved in these lesions with either amputation or radiotherapy, a prudent management course would be to defer amputation for management of local recurrences. Many patients with these lesions fail in distant sites only and die without local failure. For these patients and for those who remain long-term survivors, we believe a functional hand and foot provides a better quality of life than a prosthesis.

Rationale and Objectives: Low-osmolality contrast agents, ionic and nonionic, are being used more frequently in coronary arteriography. A new nonionic contrast agent, iopromide, has recently become available for use in clinical trials. The purpose of this phase II-phase III Food and Drug Administration (FDA) trial was to compare the side effects and diagnostic quality of iopromide with iohexol and iopamidol for coronary arteriography and left ventriculography., Methods: Two separate double-blind trials were performed using iopromide and comparison nonionic contrast agents. In the first trial, 41 patients were randomized to receive iopromide or iopamidol. The second trial was a three-center trial involving 120 patients, of whom half received iopromide (370 mg I/mL) and the other half received iohexol (350 mg I/mL). In a third study, 26 patients received iopromide (370 mg I/mL) according to an open-label design., Results: Comparison of iopromide with the other agents revealed that there were no significant differences in adverse events between iopromide and the comparison agents. Most adverse reactions were mild or moderate in severity in all patient groups. There was no difference in the patients' perceptions of heat and pain and no statistically significant difference in systolic or diastolic blood pressure at baseline, at 30 to 60 minutes, or at 24 hours after the procedure. No difference was found in the biochemical or hematologic analysis at baseline or at 24-hour follow-up. No difference between the contrast media groups in terms of the quality of the left ventriculogram or the quality of the coronary arteriography was noted., Conclusion: Compared to the other nonionic agents, iopromide showed no statistically significant differences in terms of safety or efficacy.

We describe an infant girl, born with a pigmented giant nevus, who developed a malignant schwannoma in the retroperitoneum at 16 months of age. At birth the nevus covered over 50% of her body and histologically was a compound nevus with extension into the deep dermis surrounding dermal appendages. The malignant schwannoma was biphasic with areas composed of spindle and round cells. Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell phenotype, but neuroepithelial and melanocytic cells were identified as well. We believe that this constellation of findings represents a form of neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409-429, 1974), is a disease that results from aberrations in the migration, growth, or cytodifferentiation of neural crest tissues. These diseases may be simple (a singular pathologic process, usually localized) or complex (multiple neuroectodermal lesions). We report this case because the occurrence of retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a pigmented giant nevus is unique, and may represent a previously undescribed form of a complex neurocristopathy.

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.

Each trainee in vascular medicine must be eligible for the board certification examination of the American Board of Internal Medicine or its equivalent. Training faculty, preferably at least two members, should meet the qualifications and training requirements described in this report. They must be dedicated, effective teachers and should spend most of their time in research, education and patient care related to peripheral vascular diseases. A curriculum of training should be established. Faculty experts in related specialties and in the related basic sciences should be available for teaching. The institution should have a fully equipped noninvasive vascular laboratory and areas where catheter revascularization techniques and vascular surgery are performed. The period of training should not be less than 1 year, preferably continuous.

Rationale and Objectives: A number of pressures have taken their toll on cardiovascular (CV) imaging in radiology. We conducted a survey to develop accurate information about the current status of cardiac radiology (CR) that might guide future responses and initiatives., Methods: To assess the current status of CR, a survey form was sent to all 117 active radiologist members of the North American Society for Cardiac Imaging (N = 72) and/or the Council on Cardiovascular Radiology of the American Heart Association (N = 98). The topics of inquiry included 1) present CR staffing; 2) specific adult and pediatric CR activities (cardiac plain-film interpretation, cardio-angiography (CA), echocardiography, nuclear cardiology (NC), and CV magnetic resonance imaging (MRI); 3) CR instruction of radiology residents; and 4) CR fellowship activities., Results: The survey was concluded with 64 (55%) individual responses from 58 (67%) different centers with CR groups. An overall need for CR staff (average unfilled positions/center = 0.4) was indicated. Regarding CR activities, the following were reported: 1) universal cardiac plain-film interpretation by radiologists, with most CR groups involved (adult, 64%; pediatric, 64%); 2) moderate CR contributions to CA (adult, 62%; pediatric, 57%), of which cine interpretation was the most common form (79% and 85%, respectively); 3) rare CR involvement in echocardiography (adult, 9%; pediatric, 6%); 4) low-level CR involvement in NC (adult, 16%; pediatric, 17%), but high level when combined with that of nuclear medicine (93% and 91%, respectively); and 5) almost universal radiology responsibility for CV MRI (adult, 96%; pediatric, 96%), with extensive CR involvement (77% and 82%, respectively). Of 46 reporting academic centers, most (76%) required CR training of residents; a smaller proportion (33%) of all centers offered CR fellowships., Conclusions: Because of the insights gained from this survey, recommendations can be better made to strengthen CR based on a foundation in plain-film interpretation, computed tomography, NC, and MRI.

Cardiac catheterization and angiography is a safe procedure performed on patients with suspected or potentially serious cardiovascular disorders. Complications of the procedure are related both to heart disease itself and to elements of the procedure. For a variety of social and financial reasons, the performance of cardiac catheterization and coronary angiography on an outpatient basis has increased recently. The purpose of this paper is to state the guidelines of The Society for Cardiac Angiography and Interventions regarding the performance of outpatient catheterization in a hospital setting.

Orthotopic cardiac transplantation is occasionally complicated by unexplained bradyarrhythmias. Sinus node injury as a consequence of operation or acute rejection has anecdotally been linked to the development of bradycardia early after transplantation. These arrhythmias are empirically managed by pacemaker implantation, the indications for which remain poorly defined. This retrospective study examined the 20-year experience of our institution with bradyarrhythmias after transplantation to determine the predisposing factors and indications for pacemaker implantation. Forty-one of 556 patients in our cardiac transplant program (7.4%) received permanent pacemakers between 1969 and 1989. The predominant rhythm disturbances were junctional rhythm (46%), sinus arrest (27%) and sinus bradycardia (17%). Most patients were asymptomatic (61%), and presented in the early post-transplant period (73%). Four possible predisposing factors were evaluated: (1) graft ischemic time, (2) rejection history, (3) use of bradycardia-inducing drugs, and (4) anatomy of blood supply to the sinoatrial (SA) node. No significant differences existed between patients with and without pacemakers with regard to the first 3 variables. However, after transplantation angiograms showed that prevalence of abnormal SA nodal arteries was greater in patients with than without pacemakers (p less than 0.02). Pacemaker follow-up at 3, 6 and 12 months showed persistent bradycardia (60 to 90 beats/min) in 88, 75 and 50% of patients, respectively. The most common pacemaker complication (15%) was lead displacement at time of biopsy. These results suggest that disruption of the SA nodal blood supply may be an important predisposing factor in the development of bradycardias.

Patients who are seen for medical follow-up after coronary artery bypass graft (CABG) or valve replacement (VR) surgery often present with a complex array of complaints and can be difficult to assess. We provide a summary of the components of the surgical procedure, the associated post-operative problems and potential significant complications. In addition, as an aid to simplify and direct outpatient post-operative care, we present an algorithm which addresses the expected clinical features of post-operative patients, recommended routine follow-up diagnostic tests, signs, symptoms and appropriate screening procedures for significant post-operative complications and recommendations for rehabilitation and risk factor management. This approach is designed to enable the practitioner to address these complex patients with confidence and to assist them with positive lifestyle adaptations and risk factor reduction and to predict and prevent significant post-operative complications.