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Results for “Infusions, Intralesional”

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PubMed1997

Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma.

Malignant glioblastoma may over-express the epidermal-growth-factor receptor (EGF-R). Normal brain cells show a low or no expression of EGF-R. A mouse monoclonal antibody (IgG2A) (mAb 425) (EMD55900) (Merck KGaA, Bernstadt, Germany) directed against EGF-R was produced for therapeutic use. Eight patients with primary or recurrent, EGF-R-positive glioblastomas entered the study, which was designed to evaluate the clinical effect of the mAb. In order to achieve a high tumor cell saturation, the mAb was injected intratumorally twice weekly through an implantable catheter. The total administered dose varied between 4 mg and 120 mg. In 3 patients with solid tumors, a massive tumor necrosis was noted, with infiltration of macrophages, granulocytes and T cells. A further 3 patients developed clinical and radiological signs of an intense, local, inflammatory reaction. There may be a relation between the mAb dosage and the antitumor effect, insofar as higher doses seemed to cause a more pronounced, inflammatory reaction. Of the 8 patients, 6 developed human, anti-(mouse Ig) antibodies. This anti-EGF-R mAb may induce an intense, inflammatory reaction and a considerable necrosis in glioblastoma. However, the planned schedule could not be completed, even after the dose level was re-adjusted, owing to inflammatory reactions, which were severe without prior tumor debulking.

Aged↗

PubMed1990

[Local injection of high-dose CDDP to the advanced gynecological cancer].

We investigated the efficacy of local injection of high-dose CDDP. The subjects were 16 patients with advanced gynecological cancer or tumor recurrence, in whom systemic administration of CDDP was inadvisable because of advanced age or associated complications (12 cases of cervical carcinoma, 2 cases of endometrial carcinoma, 1 case of ovarian carcinoma, and 1 case of vulvar carcinoma). In 14 cases, CDDP was injected locally to the tumor mass, using a single dose of 50-300 mg. In 2 cases, a single dose of 10-20 mg of CDDP was infused into the uterine cavity. The effects of the therapy were evaluated by cytodiagnosis, tumor markers, CT, and performance status. In all cases, an antitumor effect was noted, and seven subjects survived for at least 24 months following these therapy with CDDP. One patient developed vesicovaginal and rectovaginal fistulae after local injection of CDDP following high-dose radiotherapy. We investigated the plasma concentrations of free and total platinum after CDDP application with doses from 60-200 mg/body. Plasma concentrations showed a biphasic pattern (phase alpha and phase beta), and the peak plasma concentration of CDDP was lower than that following intravenous administration of the same dose. From these results, it was suggested that a large dose of CDDP can be injected into the tumor tissue itself and the surrounding tissue with comparatively few side effects. It will be possible to administer large dose of CDDP in this way to the terminal patients to whom there is currently no other appropriate method of treatment. The performance status of our subjects was improved, and we expect that wider use of this method will improve the quality of life for end-stage patients.

Adult↗

PubMed1996

Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty.

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.

Adult↗

PubMed1993

Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry.

A pilot study was undertaken to determine the feasibility of infusing 131I labelled monoclonal antibodies (MoAbs) into either the cavity remaining after resection of malignant glioma or into glioma cysts. Of the seven patients recruited into the study, two had cystic lesions and five resection cavities. Six of the seven were treated after relapse from primary therapy. All patients apart from one, were given a single injection of 131I conjugated to a MoAb (ERIC-1) recognising the human neural cell adhesion molecule (NCAM). One patient received a further injection of 131I-MoAb after regrowth of their disease. Pharmacokinetic studies revealed that the MoAb remained predominantly in the tumour cavity with little leakage into the systemic compartment. This resulted in a high calculated dose of radiation being delivered to the tumour cells either lining or within close proximity to the cavity/cyst wall. In such a small study, it is not possible to determine accurately response rates, but individual patient responses were observed. This, along with the low toxicity noted, demonstrates the feasibility of using 131I-MoAbs in this way. With 131I, radiation dose is deposited in tissue to a depth of 1 mm from the source. The possibility of applying isotopes such as 90Yttrium which will irradiate tumour/tissue to a greater depth (6 mm) is discussed in context with the biology of glioma infiltration into normal brain parenchyma.

Adolescent↗

PubMed1994

Intracoronary ethanol ablation in swine: characterization of myocardial injury in target and remote vascular beds.

INTRODUCTION: Physical or chemical ablation of arrhythmogenic tissue has been shown to be an effective modality of arrhythmia therapy. Chemical ablation by intracoronary infusion of ethanol into a specific coronary artery bed has been demonstrated, but the characteristics and distribution of necrosis relative to the coronary blood supply have not been delineated. METHODS AND RESULTS: A total of 40 myocardial lesions were created in 21 pigs by infusion of 1.6 +/- 0.6 mL of 50% ethanol and 50% iohexol contrast solution through a 2.7 French infusion catheter advanced into a branch of the left anterior descending or circumflex coronary artery. Prior to ethanol infusion, 5.3 +/- 1.2 mCi technetium-99m (Tc-99m) methoxyisobutyl isonitrile (sestamibi) was infused into the coronary branch in order to delineate the perfusion bed. After completion of the lesions, each heart was removed, sliced transversely in 5-mm slices, and stained with nitro blue tetrazolium in order to define the ablation bed. The slices were then imaged with a gamma camera and the area of Tc-99m sestamibi uptake was defined as the perfusion bed. These respective areas were planimetered for each slice and compared. No difference was observed in hemodynamic parameters between preablation and postablation measures except mean arterial pressure, which fell from 122 +/- 22 mmHg to 116 +/- 24 mmHg (P = 0.02). Significant ventricular arrhythmias were observed after 60% of the ablations. The mean left ventricular ejection fraction fell from 55% +/- 9% to 45% +/- 15% after completion of all ablations. The areas of the ablation beds were related to the areas of the perfusion beds but the correlation was poor (r = 0.41, P = 0.0001). Generally, the ablation bed was smaller than the perfusion bed, but evidence of ethanol reflux was observed in 29% of the lesions resulting in injury beyond the targeted perfusion bed. CONCLUSIONS: Intracoronary ethanol ablation is a promising technique for the treatment of arrhythmias. Significant arrhythmias and a decrease in left ventricular ejection fraction are associated with this technique. Lesions are generally produced within the distribution of the targeted coronary bed, but are also frequently associated with reflux to a second vascular distribution.

Animals↗

PubMed2001

The influence of intraarterial prostaglandin E(1) on vascular hydraulic impedance and infrainguinal graft patency.

OBJECTIVES: To evaluate the influence of intraoperative arterial prostaglandin E(1)(alprostadil) infusion on hydraulic impedance in relation to graft patency. METHODS: Hydraulic impedance was measured in 115 infrainguinal bypasses by means of the extracorporeal-bypass-flow method (EBF). Fifty-eight femoro-popliteal and 57 femoro-crural polytetrafluoroethylene (PTFE) grafts were included. 10 microg of alprostadil were administered into a temporary bypass and the haemodynamic changes were recorded. The reactions of input (Z(x)) and characteristic (Z(0)) impedances as well as phase relations were derived and related to graft outcome after three years. RESULTS: Significant changes after administration of prostaglandin were observed for overall pressure (74 vs. 84 mmHg, p<0.01), flow rate (194 vs 160 ml/min, p<0.01), input impedance (0.55 vs. 0.75 PRU, p<0.01) and the phase angle of the first harmonic (-18 degrees vs -26 degrees, p<0.01). An increase of at least one degree of the first harmonic phase angle following alprostadil injection in the crural bypass group was associated with a significant better graft prognosis of crural (p<0.01) but not popliteal grafts. Primary and secondary patency rates after three years for crural grafts with an increase of at least one degree were 62% and 63% (n=45) and for non-responders 18% and 0% (n=12, p(prim)<0.01, p(sec)<0.001). All crural bypasses with poor prostaglandin reaction occluded within 9 months (n=12) after the operation. CONCLUSIONS: The EBF method allows a combined assessment of peripheral resistance and impedance parameters. The response of the first harmonic phase angle provides important predictive information regarding femoro-crural grafts.

Adult↗

PubMed1998

The effects of prenatal intraamniotic surfactant or dexamethasone administration on lung development are comparable to changes induced by tracheal ligation in an animal model of congenital diaphragmatic hernia.

BACKGROUND/PURPOSE: Lung surfactant deficiency contributes to the pathophysiology of congenital diaphragmatic hernia (CDH) and the high neonatal mortality rate. Acceleration of lung surfactant system maturation by prenatal administration of hormones has been described in animal models of CDH. However, in utero tracheal ligation (TL) is the best method to accelerate lung growth and reverse the pulmonary hypoplasia associated with CDH. Although this method offers promise, its application in humans is limited. The aim of this study was to investigate a new noninvasive therapeutic strategy, that is, the prenatal intraamniotic administration of exogenous porcine surfactant or dexamethasone, and compare it with the effects of TL in an animal model of CDH. METHODS: Twenty-four pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 to create CDH in 26 fetuses. Five groups of animals were studied: (1) Control, nonoperated fetuses (n=14), (2) CDH (n=6), (3) CDH plus TL (n 6), (4) CDH plus intraamniotic administration of Curosurf (40 mg; n=6), and (5) CDH plus intraamniotic infusion of dexamethasone (0.4 mg; n=8). On gestational day 30, the fetuses were delivered by cesarean section. Functional studies (lung hysteresis curves and lung distensibility), weight and volume of lungs, histopathologic and histomorphometric analysis of lungs were performed. RESULTS: The authors demonstrated that the hysteresis curve of CDH animals was shifted downward in comparison with controls. The analyses of curves standardized for lung weight indicated that intraamniotic administration of surfactant or dexamethasone improved lung compliance in comparison with controls and CDH fetuses, but TL had no effect on this parameter. Lung distensibility (maximum lung volume at 32 cm of water pressure per gram of lung) was reduced by CDH, but this parameter was increased by intraamniotic administration of drugs and not by TL (P< .05). CDH decreased the weight and volume of lungs (P< .05), and these changes were reversed only by TL, which prevented the herniation of the liver from the abdomen to the thorax. Histologically, CDH lungs treated with TL or intraamniotic administration of drugs demonstrated structural patterns similar to those of controls. Histomorphometric studies proved that CDH promoted significant thickening of septa walls (P< .05), and all the therapeutic methods could reverse this alteration to control values. The alveolar number per area in control lungs, CDH, and CDH plus TL lungs were similar, but in CDH plus surfactant and CDH plus dexamethasone lungs, the decreased number per area (P< .05) demonstrated that the alveolar airspace was increased. CONCLUSION: From these data the authors conclude that intraamniotic surfactant or dexamethasone administration is capable of preventing pulmonary hypoplasia in fetuses with CDH, and thus, this method may be a substitute for TL.

Analysis of Variance↗

PubMed1997

Indication of chemoembolization therapy without gelatin sponge for hepatocellular carcinoma.

This study evaluated the effect of chemoembolization (C-LIP) consisting of ethiodized oil (Lipiodol Ultra Fluid; André Guerbet, Aulnay-sous-Bois, France) and epirubicin, without gelatin sponge on hepatocellular carcinoma (HCC), administered by hepatic arterial infusion. We analyzed the cases from two points of view: the local recurrence rate for hypervascular solitary small HCC (tumor size: < or =3 cm in diameter) and the cumulative survival rate for advanced HCC (stage VI according to the criteria of Liver Cancer Group of Japan) following C-LIP therapy. The C-LIP also was compared with transcather arterial embolization (TAE; C-LIP followed by gelatin sponge) and percutaneous ethanol injection therapy (PEIT). In the small HCC cases, the recurrence rate at 1 year after C-LIP was 77% (10 of 13 patients), while the local recurrence rate was 46% (six of 13 patients) at 6 months and 61% (eight of 13 patients) at 1 year. The local recurrence rate at 1 year was 29% (four of 14 patients) after TAE and 20% (three of 15 patients) after PEIT. These results showed that the effect of local anticancer therapy by C-LIP was not as potent as that of TAE or PEIT. In advanced HCC cases, the cumulative survival rate for 13 patients treated by C-LIP was 72% at 6 months, 36% at 1 year, and 14% at 2 years. However, the survival rates for 13 patients at 6 months, 1 year, and 2 years after TAE were 46%, 23%, and 8%, respectively. There was no difference between the C-LIP patients and TAE patients with regard to the pretreatment liver function. Three patients died within 2 months after the initial TAE. These deaths were mainly due to damage to the noncancerous liver parenchyma. Therapy with C-LIP alone was not appropriate for hypervascular solitary small HCCs, and additional treatment was necessary. We think C-LIP therapy should be selected instead of TAE for advanced HCCs to avoid severe parenchymal damage.

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