Age-related aspects of balloon angioplasty for postsurgical aortic recoarctation

Balloon angioplasty is now the elective technique for relief of aortic recoarctation, since it has low mortality, low morbidity, and good results at follow-up. Some concern exists concerning the possible increased risk in young children. To investigate such age-related aspects, we examined 58 children undergoing consecutive balloon angioplasty for postsurgical recoarctation. Of the children, 30 were younger and 28 older than 1 year. Recoarctation was more frequent with ventricular septal defect or other cardiac anomalies (p < 0.001). Systolic hypertension was present in 70% of children aged less than 1 year, but in only 32% of those older than 1 year (p < 0.001). The initial gradient was inversely related with the age at dilation (r = -0.28, p < 0.05), and correlated with systolic blood pressure (r = 0.81, p < 0.01). The procedure was successful in 87% of children older than, and 86% of those under 1 year. Age was not related with residual gradient, nor with the percentage increase of diameter of the site of stenosis. After balloon angioplasty, systolic hypertension was still present in 37% of children younger than 1 year, and in 25% of those older than 1 year (p < 0.05). Three complications occurred in children younger than 1 year, and 6 in those older (p < 0.05). Our results show, first, that recoarctation occurs earlier in the setting of complex disease, second that children suffering recoarctation at a younger age are more likely to be hypertensive, either before or after balloon angioplasty, third, that balloon angioplasty has the same rate of success in children below or above the age of one year, although the procedure still carries a not negligible risk. Finally, the procedure does not carry a higher risk for those children below the age of 1 year.     

Use of bovine jugular vein to reconstruct the right ventricular outflow tract: early results

OBJECTIVE: We evaluate early results of bovine jugular vein conduits in the pulmonary outflow. METHODS: Between April 2000 and September 2001, 31 conduits were placed in the outflow of the right ventricle. Patients who received a conduit as a staged surgical procedure were excluded (n = 3). Implantation age ranged from 0 to 21 years (median, 3.4 years). Conduit diameter ranged from 12 to 20 mm (median, 14 mm). Transthoracic echocardiography was performed at discharge and 3 months after surgery. Patients with significant pulmonary regurgitation and/or stenosis underwent cardiac catheterization. RESULTS: Four patients died during the follow-up period. Three deaths were unrelated to the conduit. One death was related to the complete thrombosis of the conduit. At 3 months evaluation, pulmonary valve regurgitation was absent or trivial in 19, mild in 2 and severe in 3 of 24 survivors. Four patients had nonfatal conduit-related complications. A transient thrombus formation within 1 leaflet was noted postoperatively in a patient with a moderate pulmonary regurgitation. Three patients required reoperation 3 to 5.8 months after the implantation for conduit failure (mean, 4.3 months). Cardiac catheterization before replacement revealed an aneurysmal dilation of the conduit below a severe stenosis of the pulmonary bifurcation due to important neointimal proliferation. CONCLUSIONS: Early failure of bovine jugular vein valved conduits can occur because of exaggerated intimal proliferation or thrombotic process within the conduit. Because of these complications, close echocardiographic follow-up is mandatory during the first weeks after implantation.     

Pentostatin in T-non-Hodgkin's lymphomas: efficacy and effect on CD26+ T lymphocytes

Pentostatin is an adenosine deaminase (ADA) inhibitor with antineoplastic activity. CD26 is a surface glycoprotein with a key role in T cell function as the ADA binding protein. We conducted a phase II study to evaluate pentostatin efficacy in relapsed T-non-Hodgkin's lymphoma (T-NHL) and to correlate response with tumor CD26 expression. We also examined the lymphopenic effect of pentostatin on CD26+ T lymphocytes. Eighteen patients were registered for the study. Pentostatin was administered as intravenous bolus daily over 3 days at an initial dose of 5 mg/m(2)/day, repeated every 4 weeks. CD26 surface expression on tumor cells and T lymphocytes was determined by flow cytometry. Out of 14 patients evaluable for response, there was 1 (7%) complete response (CR) and 6 (43%) partial responses (PR). Median progression-free survival for responders was 6 months (range: 2-15 months); median number of courses was 4 (range: 1-6). Responders included 1 of 2 CD26+ and 5 of 9 CD26- cases. Pentostatin also specifically depleted CD26+ rather than CD26- T lymphocytes, potentially associated with immunosuppression. We therefore conclude that while pentostatin is a safe and active agent for T-NHL regardless of CD26 expression, it may selectively deplete CD26+ T lymphocytes, with potentially significant clinical implications.     

Expression of CD40 ligand (CD154) in B and T lymphocytes of Hodgkin disease: potential therapeutic significance

BACKGROUND: The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express CD30 and CD40 receptors that can activate nuclear factor kappa B and transduce survival signals. The authors have reported previously that the B lymphocytes of HD express CD30 ligand (CD30L, CD153). Furthermore, they and others have reported previously that the CD40L survival pathway is augmented in patients with B-cell malignancies, as CD40L was constitutively expressed by the malignant B cells and infiltrating T cells, and sera from those patients contained elevated levels of soluble CD40L. In this study, the authors investigated the hypothesis that the survival of H/RS cells was similarly promoted by an augmented CD40L signals in HD patients. METHODS: The expression of CD40L on lymphocyte subsets of patients with classic HD was determined by two-color fluorescent-activated cell sorter analysis. Serum soluble CD40L levels were determined by enzyme linked immunosorbent assay. RESULTS: CD40L was constitutively expressed on both the T and B cells of HD patients but was more prominently expressed on the B lymphocytes. Soluble CD40L was detected in the serum of 17 of 37 patients (45%) and was higher than 1 ng/mL in 4 patients (10%). Both interleukin (IL)-4 and IL-10, which are known to be secreted by H/RS cells and surrounding T cells, up-regulated CD40L expression on normal B cells. CONCLUSIONS: Thus, the expression of CD40L and CD30L on the B cells of HD patients suggests that B lymphocytes may play a role in the regulation of H/RS cell growth in vivo. Depriving H/RS cells from CD30L and CD40L survival signals by eliminating B cells from HD lesions may be of therapeutic value.     

Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma

Vascular endothelial growth factors (VEGF) are secreted by many tumor types, and are believed to affect tumor growth by promoting angiogenesis through binding to their receptors present on vascular endothelium. Recently, mRNA for VEGF-C the ligand for VEGFR-3, was found to be up-regulated in colorectal adenocarcinoma (CRC). The aim of this work was to determine: 1) the distribution of VEGF-C and VEGFR-3 in CRC, and 2) the biological significance of such expression. Sections of formalin-fixed and paraffin-embedded tissues from 56 CRC were immunohistochemically stained for VEGF-C and VEGFR-3. The type and percent of positive cells was recorded. Survival analysis was performed using the Kaplan-Meier method. All CRC were positive for VEGF-C which was present in the cancer cells themselves, as well as in stromal cells. Normal colon epithelium was usually negative. Only ten (17%) of the 56 CRC completely lacked VEGFR-3 expression. VEGFR-3 immunoreactivity was detected in <25% of the cancer cells in 22 cases and in >25% of the cells in 34 cases. Expression of VEGFR-3 in >25% of the cancer cells was associated with significantly poorer overall survival (p<0.05), but not with lymph node metastasis or depth of tumor invasion. Our results suggest that VEGFs promote cancer growth not only by stimulating angiogenesis, but also by acting on receptors present on the cancer cells themselves.     

Long-Term Toxicity after Transarterial Radioembolization with Yttrium-90 Using Resin Microspheres for Neuroendocrine Tumor Liver Metastases

Purpose

To evaluate long-term effects of yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE) for unresectable hepatic metastases of neuroendocrine tumors (NETs).

Influence of hypoxia and hyperoxia on the cardiovascular and lethal effects of ethanol

The mutual potentiation of the hepatotoxic effects of ethanol and hypoxia raised the question of whether such an interaction also occurs in the cardiovascular system. Therefore, anaesthetized rats were infused intravenously with ethanol (25 mg/kg x min.) over 90 min. to reach blood ethanol concentrations between 2.2 and 2.6 g/l and were ventilated artificially either with room air, 10% O2/90% N2 or 100% O2. Under normoxic conditions, ethanol produced a slow decrease of mean arterial blood pressure from 130 to 100 mmHg due to the decline in cardiac output and stroke volume (-20%) while heart rate and peripheral resistance remained unchanged. Hypoxia (arterial oxygen tension 35-38 mmHg) without ethanol produced immediate hypotension (-60 mmHg) without decreasing the cardiac output, i.e. by reducing peripheral resistance. In combination with ethanol, hypoxia produced an even stronger hypotension (-90 mmHg) due to reduction in both cardiac output and peripheral resistance. On the other hand, respiration with 100% O2 (arterial oxygen tension about 500 mmHg) elevated peripheral resistance, attenuated ethanol-induced cardiodepression and prevented ethanol-induced hypotension. The lethal doses of ethanol evaluated by infusing 75 mg/kg x min. ethanol until death amounted to 4.1 g/kg with 10% O2, to 5.5 g/kg with 20% O2 (room air) and to 6.9 g/kg with 100% O2. Thus decrease in vascular contractility induced by hypoxia combined with ethanol-induced cardiodepression may result in lethal cardiovascular failure. Hyperoxia, on the other hand, counteracts ethanol-induced cardiodepression and its acute toxicity by raising the vascular contractility.