Efficacy, toxicities, and prognostic factors of stereotactic body radiotherapy for unresectable liver metastases.

INTRODUCTION: This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery. METHODS: This study included 31 consecutive patients with unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival. RESULTS: Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer). CONCLUSION: Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.

Peak filling rate normalized to mitral stroke volume: a new Doppler echocardiographic filling index validated by radionuclide angiographic techniques.

The noninvasive measurement of left ventricular filling has relied predominantly on radionuclide-derived peak filling rate normalized to end-diastolic volume. Doppler echocardiography also has the ability to measure peak filling rate, but wide application of this technique has been limited by technical errors involved in quantitative echocardiographic determination of mitral anulus cross-sectional area and ventricular volumes. For Doppler echocardiography, normalization of peak filling rate to mitral stroke volume rather than end-diastolic volume permits the derivation of a diastolic filling index that is relatively free of errors caused by geometric assumptions, diameter measurements and sample volume positioning. This normalization process can be achieved by simply dividing early peak filling velocity by the time velocity integral of mitral inflow. To validate this new Doppler echocardiographic filling index, Doppler echocardiographic and radionuclide-derived peak filling rate, both normalized to mitral stroke volume, were compared in 30 patients; there was an excellent correlation (r = 0.91, SEE = 0.88). This variable was not influenced by the position of the sample volume in relation to the mitral apparatus in contrast to early filling velocity, which increased 37%, and early/late filling (E/A) ratio, which increased 43% as the sample volume was moved from the anulus to the tips of the mitral leaflets. In a cohort of 22 normal patients, the mean peak filling rate normalized to mitral stroke volume (SV) was 5.25 +/- 1.47 SV/s. The mean peak filling rate for a subgroup of eight normal patients aged 57 to 89 years (mean 71 +/- 9) was 3.9 +/- 1 SV/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic value of noninvasive testing one year after orthotopic cardiac transplantation.

OBJECTIVES: We sought to evaluate the prognostic value of routine noninvasive testing--stress thallium-201 imaging, rest two-dimensional echocardiography and rest equilibrium radionuclide angiography--1 year after cardiac transplantation. BACKGROUND: Coronary artery vasculopathy is the most important cause of late death after orthotopic cardiac transplantation. Several clinical variables have been identified as risk factors for development of coronary vasculopathy. Traditional noninvasive diagnostic testing has been shown to be relatively insensitive for identifying patients with angiographic vasculopathy. METHODS: Results of prospectively acquired noninvasive testing in 47 consecutive transplant recipients alive 1 year after transplantation were related to subsequent survival. Other clinical variables previously shown to be associated with the development of coronary artery vasculopathy were also included in the analysis. RESULTS: The 5-year survival rate after cardiac transplantation was 81%. By univariate analysis, echocardiography (chi-square 9.21) and stress thallium-201 myocardial perfusion imaging (chi-square 16.76) were predictive for survival, whereas rest equilibrium radionuclide angiography was not. Clinical contributors to survival were donor age (chi-square 4.56), number of human leukocyte antigen mismatches (chi-square 3.06) and cold ischemic time (chi-square 3.23). By multivariate analysis, stress myocardial imaging remained the only significant predictor of survival (risk ratio 0.27; 95% confidence interval 0.06 to 0.89). CONCLUSIONS: Normal thallium-201 stress myocardial perfusion imaging 1 year after cardiac transplantation is an important predictor of 5-year survival.

The feasibility of high-dose chemotherapy in breast cancer patients with impaired left ventricular function.

Breast cancer patients with cardiac disease are usually excluded from clinical trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or metastatic disease with sequential high-dose melphalan and stem cell rescue followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA) at baseline, after each course of chemotherapy and 4 weeks after completing both transplants. The mean absolute decrease in LVEF after the two transplants was 3.6% (P = 0. 008 for the comparison with baseline LVEF), and most of this drop (-2.5%, P = 0.007) occurred after mobilization. Unexpectedly, paclitaxel was associated with a mean absolute decrease in LVEF of 3. 4% (P = 0.032, n = 19), cyclophosphamide alone was not associated with a significant change in LVEF (-1.3%, P = 0.23), but mobilization with sequential paclitaxel and cyclophosphamide resulted in a mean absolute drop of 4.9% in LVEF (P = 0.009). Twelve patients were found to have a reduced LVEF (<50%) at least once during treatment and had a mean absolute decrease in LVEF of 10% (P = 0.008) from baseline, compared with a drop of only 1.8% (P = 0. 176) in the patients without impaired LV function. Although two of these 12 patients developed symptomatic heart failure, their cardiac symptoms were easily treated and there were no cardiac deaths. We conclude that our protocol has acceptable cardiac toxicity and breast cancer patients with impaired LV function should not be denied high-dose chemotherapy if otherwise indicated.

Heart transplant rejection with hemodynamic compromise: a multiinstitutional study of the role of endomyocardial cellular infiltrate. Cardiac Transplant Research Database.

BACKGROUND: The natural history of patients experiencing hemodynamic compromise with rejection has been incompletely characterized. This multiinstitutional study examined the outcome of such episodes, particularly with regard to the extent of cellular infiltrate on the index endomyocardial biopsy. METHODS: From January 1, 1990, through June 30, 1994, 3367 patients in the Cardiac Transplant Research Database experienced 4137 episodes of rejection. Severe hemodynamic compromise occurred in approximately 5% of the rejection episodes, and this proportion remained relatively constant over time. RESULTS: Recipient risk factors for rejection with severe hemodynamic compromise included black race, female recipient sex, and diabetes. The 3-month actuarial survival rate was 60% after rejection with severe hemodynamic compromise versus 95% after rejection with no or mild compromise. Low initial biopsy score conferred a higher early survival, but a lower survival at 2 years after rejection with severe hemodynamic compromise. Among patients who survive an initial rejection episode with severe hemodynamic compromise, survival at 2 years after an episode was 46% among those who had a low initial biopsy score versus 84% with a high biopsy score. CONCLUSIONS: Rejection with hemodynamic compromise, although rare, represents a major complication of heart transplantation with a poor long-term outcome. Survivors of hemodynamically compromising rejection episodes associated with low biopsy scores in the International Society for Heart and Lung Transplantation grading system have a significantly worse long-term outcome than survivors of episodes associated with high scores. These findings suggest that immunologic mechanisms other than lymphocytic infiltration of the cardiac allograft are important and distinct causes of allograft dysfunction.

A bending energy model for measurement of cardiac shape deformity.

An approach to analyzing and quantifying the shape characteristics of the endocardial contour of the left ventricle of the heart is described. The computation begins by finding the local curvature differences between the contour under consideration and the mean normal contour at each of 100 equidistant points. The weighted square of these differences, summed over a set of points, is shown to be the regional or, global bending energy required to deform the mean normal contour to the characteristic shape of the analyzed contour. Resampling, smoothing and curvature computation issues are considered for the image-derived digital contours that are used in the analysis. Experiments were performed on artificial contour data and data derived from contrast ventriculographic (CV) studies of humans. It is also shown that the method has been adapted to measure endocardial shape form equilibrium radionuclide angiocardiography.

Hemodynamics of the right ventricle in normal and disease states.

The physiology and hemodynamic functions of the right ventricle in normal and disease states differ considerably from those of the left ventricle. To illuminate these differences, the right ventricle's essential functions in the normal circulation are reviewed, its functional anatomy and blood supply are described, principles and methods of systolic function assessment are discussed, and hemodynamic adaptations to selected diseases causing chronic right-side volume and pressure overload are highlighted.

Treatment of the hemodynamically unstable patient.

The pathogenesis, diagnosis, and management of six clinical syndromes associated with acute myocardial infarction and hemodynamic instability are discussed: (1) autonomic disturbances with hypertension-tachycardia or hypotension-bradycardia; (2) pulmonary edema; (3) cardiogenic shock; (4) right ventricular infarction; (5) rupture of ventricular free wall or septum; and (6) papillary muscle rupture.

Medical therapy and prognosis in chronic heart failure. Lessons from clinical trials.

The past two decades have witnessed tremendous advances in the pharmacologic therapy of patients with left ventricular dysfunction and chronic heart failure. The pharmacologic repertoire has been and continues to be expanded with newer agents carefully subjected to the rigor of well-designed clinical trials. Treatment has consequently evolved from pathophysiologically guided therapy predicated on older concepts to evidence-guided therapy supported by results of major clinical trials that continue to expand the understanding of the pathophysiology of this complex syndrome. The goals of therapy have ambitiously evolved from the immediate symptomatic relief offered by diuretics; to the short-term hemodynamic improvement in the circulation produced by direct vasodilators; to the intermediate-term improvement in functional capacity and exercise tolerance associated with vasodilators, nitrates, and digoxin; and to the final frontier of long-term improvement in morbidity and survival associated with ACE inhibitor therapy. In addition to the expansion of the understanding of the epidemiology, natural history, and pathophysiology of chronic heart failure, several important lessons in clinical pharmacology have been learned from the clinical trials of the last decade. Many other questions, however, remain unanswered. The role of diuretics, although uncontested in the acute stabilization of congested patients, has yet to be rigorously evaluated in stable patients with chronic left ventricular dysfunction on ACE inhibitors. The long-term effects of nitrates on morbidity and mortality have not yet been established in patients with either ischemic or nonischemic ventricular dysfunction. Vasodilators as a class, and perhaps because they are not a homogeneous class, have had a mixture of successes and failures. There is no evidence that pure vasodilation in and by itself improves survival. There is ample evidence, however, that it improves the circulation and consequently the response to diuretics. This improvement may translate into intermediate-term improvement in functional capacity, but this benefit is seldom sustained. Hemodynamic improvement in the circulation may not always translate into longer-term improvement in morbidity and reduction in mortality. The syndrome of chronic heart failure from systolic left ventricular dysfunction has emerged as a disease of mechanical dysfunction and maladaptation. The maladaptation is a consequence of deleterious effects of compensatory neurohormonal mechanisms: the sympathetic nervous system, renin-angiotensin-aldosterone system, arginine vasopressin, and most likely a host of other mechanisms. The degree of activation of these mechanisms has been established as a marker of prognosis, and the effects of pharmacologic agents on these mechanisms may well determine their long-term effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities found on cephalometric radiographs.

The films of 513 consecutive patients from a private practice were brought to Children's Hospital, Los Angeles for reading in their Radiology Department. Eighteen films, 3.5 percent, were classified as having abnormalities or pathologies present. In addition, there were seven findings labeled as interesting, although normal, because they are usually not present on the lateral head film. The lateral orthodontic cephalometric head film can disclose a variety of pathoses which are significant to the physician. The orthodonitist sholld study the lateral head roentgenogram for nondental abnormalities.