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Biomedical subjects

P Moroz

Publications and source records attributed to P Moroz.

12 recordsLinked to original sources
PubMed2003

A magnetic resonance imaging based method for measurement of tissue iron concentration in liver arterially embolized with ferrimagnetic particles designed for magnetic hyperthermia treatment of tumors.

Rabbit liver was loaded with ferrimagnetic particles of gamma -Fe2 O3 (designed for magnetic hyperthermia treatment of liver tumors) by injecting various doses of a suspension of the particles into the hepatic artery in vivo. Proton transverse relaxation rate (R(2)) images of the livers in vivo, excised, and dissected were generated from a series of single spin-echo images. Mean R(2) values for samples of ferrimagnetic-particle-loaded liver dissected into approximate 1 cm cubes were found to linearly correlate with tissue iron concentration over the range from approximately 0.1 to at least 2.7 mg Fe/g dry tissue when measured at room temperature. Changing the temperature of ferrimagnetic-particle-loaded samples of liver from 1 degrees C to 37 degrees C had no observable effect on tissue R(2) values. However, a small but significant decrease in R(2) was found for control samples containing no ferrimagnetic material on raising the temperature from 1 degrees C to 37 degrees C. Both chemically measured iron concentrations and mean R(2) values for rabbit livers with implanted tumors tended to be higher than those measured for tumor-free liver. This study indicates that tissue R(2) measurement and imaging by nuclear magnetic resonance may have a useful role in magnetic hyperthermia therapy protocols for the treatment of liver cancer.

Animals↗
PubMed2001

Status of hyperthermia in the treatment of advanced liver cancer.

The vast majority of patients with malignant liver tumors have inoperable disease. These patients must rely on chemotherapy, radiotherapy, and various locoregional treatments. Although these treatments have demonstrated encouraging response rates, symptom palliation and occasional down staging of tumors, their impact on survival is minor. As a result there has been renewed interest in hyperthermia as a treatment option. This study reviews the current modalities of hyperthermia in terms of clinical results, side effects, limitations, and therapeutic standing.

Carcinoma, Hepatocellular↗
PubMed2001

Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model.

BACKGROUND AND OBJECTIVES: Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS: Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS: The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS: Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.

Animals↗
PubMed2001

Effect of selective internal radiation therapy and hepatic arterial chemotherapy on normal liver volume and spleen volume.

OBJECTIVE: To determine the effect of selective internal radiation therapy (SIRT) and hepatic arterial chemotherapy (HAC) on normal liver volume and spleen volume in patients receiving these treatments for advanced liver cancer. METHODS: In a phase III clinical trial to assess the benefit of SIRT over HAC one group of patients received SIRT + HAC while a second group received HAC only. All patients in this trial who had abdominal CT scans available before treatment, and at 3, 6, and 12 months after treatment were evaluated. Changes in normal hepatic parenchyma (NHP) volume, portal vein diameter and spleen volume were calculated for each patient and analysed for significant trends. RESULTS: The mean NHP volume decreased by 17% (P = 0.001) 12 months after treatment among patients receiving SIRT + HAC (N = 22), while the mean NHP volume among patients treated with HAC only (N = 15) was unchanged at 12 months. The mean portal vein diameter increased by 9% in both treatment groups, P = 0.048 and P < 0.001, respectively. The mean spleen volume increased by 48% (P < 0.001) and 26% (P = 0.001), respectively, in the two groups 12 months after treatment started. There was no clinical evidence of hepatic failure, portal hypertension or splenic dysfunction in any of the patients. CONCLUSIONS: Treatment of patients with SIRT + HAC causes contraction of the normal hepatic parenchyma, while treatment with HAC alone has no significant effect. Treatment with either SIRT + HAC or HAC alone causes a significant increase in portal vein diameter and spleen volume by 12 months after treatment. The increase in spleen volume and portal vein size is likely to be due to portal hypertension resulting from scarring within the liver as a result of chemical and radiation hepatitis.

Aged↗
PubMed2001

Randomised trial of SIR-Spheres plus chemotherapy vs. chemotherapy alone for treating patients with liver metastases from primary large bowel cancer.

PURPOSE: SIR-Spheres are radioactive yttrium90 microspheres (SIR-Spheres, Sirtex Medical Limited, Australia) used to selectively target high levels of ionising radiation to tumors within the liver. This trial was designed to measure any increased patient benefit by adding a single administration of SIR-Spheres to a regimen of regional hepatic artery chemotherapy (HAC) administered as a 12 day infusion of floxuridine and repeated at monthly intervals, vs. the same chemotherapy alone. PATIENTS AND METHODS: A phase III randomised clinical trial entering 74 patients was undertaken on patients with bi-lobar non-resectable liver metastases from primary adenocarcinoma of the large bowel. Patient benefit criteria assessed in the trial were tumor response, time to disease progression in the liver, overall survival, quality of life, and treatment related toxicity. Tumor response was measured by serial changes in both cross-sectional tumor areas and total tumor volumes, provided any response lasted not less than three months as well as changes in serum carcino-embryonic antigen (CEA). RESULTS: The partial and complete response rate (PR + CR) was significantly greater for patients receiving SIR-Spheres when measured by tumor areas (44%) vs. 17.6%, P = 0.01) tumor volumes (50% vs. 24%, P = 0.03) and CEA (72% vs. 47%, P = 0.004). The median time to disease progression in the liver was significantly longer for patients receiving SIR-Spheres in comparison to patients receiving HAC alone when measured by either tumor areas (9.7 vs. 15.9 months, P = 0.001), tumor volumes (7.6 vs. 12.0 months, P = 0.04) or CEA (5.7 vs. 6.7 months, P = 0.06). The one, two, three and five-year survival for patients receiving SIR-Spheres was 72%, 39%, 17% and 3.5%, compared to 68%, 29%, 6.5% and 0% for HAC alone. Cox regression analysis suggests an improvement in survival for patients treated with SIR-Spheres who survive more than 15 months (P = 0.06). There was no increase in grade 3-4 treatment related toxicity and no loss of quality of life for patients receiving SIR-Spheres in comparison to patients receiving HAC alone. CONCLUSION: The combination of a single injection of SIR-Spheres plus HAC is substantially more effective in increasing tumor responses and progression free survival than the same regimen of HAC alone.

Adenocarcinoma↗
PubMed2000

Kinetics of very-low-density lipoprotein apolipoprotein B-100 in normolipidemic subjects: pooled analysis of stable-isotope studies.

To further explore the physiology of very-low-density lipoprotein (VLDL) apolipoprotein B-100 (apoB), we performed a pooled analysis of 21 reports based on the intravenous administration of stable isotope-labeled amino acids in a total of 154 healthy normolipidemic subjects. Prandial status was the most significant independent predictor (P < .001) of the hepatic secretion of apoB, which was higher in the fed state compared with the fasted state (1,819 +/- 188 v 1,046 +/- 61 mg/d, P < .001). In the fed state, apoB secretion increased with age (P = .003) and tended to be higher in men compared with women (P = .0065). The fractional catabolism of VLDL apoB decreased with weight (P = .0038) and was lower in men versus women (8.38 +/- 0.55 v 12.59 +/- 1.65 pools/d, P = .007), as well as patients that were carriers of the E4 allele compared with those who were not carriers of this allele (5.52 +/- 0.49 v 9.58 +/- 0.87 pools/d, P < .001). The VLDL apoB concentration in both the fed and fasted states was dependent on both the rate of hepatic production and fractional clearance of apoB. Plasma cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations in the fasted state were principally determined by the fractional catabolism of VLDL apoB (P< .005). These findings suggest that under physiologic conditions in healthy individuals, the transport of VLDL apoB in plasma is predominantly determined by age, sex, body weight, apoE genotype, and prandial status.

Apolipoprotein B-100↗
PubMedDate not supplied

The effect of tumour size on ferromagnetic embolization hyperthermia in a rabbit liver tumour model.

OBJECTIVE: Ferromagnetic Embolization Hyperthermia (FEH) consists of arterially embolizing tumours with ferromagnetic particles to cause hysteretic heating upon subsequent exposure to an alternating magnetic field. The objective was to determine the effect of tumour size during FEH using a rabbit liver tumour model. METHOD: Thirty-three rabbits containing implanted hepatic VX2 carcinomas received a hepatic arterial infusion of ferromagnetic particles suspended in lipiodol. Following hysteretic heating, tumour and normal hepatic tissues were chemically analysed for iron content. Tumours were classed as small if their mass was less than the median mass for the whole group of subjects (2.1 g), and as large if their mass was greater than or equal to the median. To control for variability in tumour iron concentration, 13 small tumours were matched to 13 large tumours by iron concentration, and their heating characteristics compared. RESULTS: The heating rate in large tumours (median = 5.0 degrees C/min) was significantly greater than that in the matched small tumours (median = 2.8 degrees C/min), p = 0.006. Regression analysis determined that the slope of the heating rate vs iron concentration curve for large tumours was 1.5 times greater than that for the matched small tumours, p < 0.001. After cessation of heating in large tumours, there was continued heat dissipation into surrounding tissues, which led to anomalous temperature increases. There was an inverse linear relationship between tumour size and tumour iron concentration for a given dose of particles. CONCLUSION: For a given tumour iron concentration, larger tumours heat at a greater rate than small tumours, due to the poorer tissue cooling and better heat conduction in the necrotic regions of large tumours. This warrants further investigation as this finding could confer a significant advantage on FEH over other hyperthermic modalities in the treatment of hepatic malignancies.

Animals↗
PubMedDate not supplied

Magnetically mediated hyperthermia: current status and future directions.

The use of hyperthermia in the treatment of cancers is appealing because, as a physical therapy, hyperthermia would have far fewer restrictive side effects than chemotherapy and radiotherapy, and it could be used in combination with these therapies. However, the currently available modalities of hyperthermia are often limited by their inability to selectively target tumour tissue and, hence, they carry a high risk of collateral organ damage or they deposit heat in a very localized manner which can result in under-treatment of a tumour. Magnetically mediated hyperthermia (MMH) has the potential to address these shortcomings. MMH consists of the localization of magnetic particles or seeds within tumour tissue followed by exposure to an externally applied alternating magnetic field to cause them to heat. Since this concept was introduced (over 40 years ago), MMH has evolved into four general sub-classes: arterial embolization hyperthermia (AEH), direct injection hyperthermia (DIH), intracellular hyperthermia (IH) and interstitial implant hyperthermia (IIH). It is the purpose of this article to review these four sub-classes in terms of experimental or clinical results, advantages, limitations and current status.

Humans↗
PubMedDate not supplied

Hepatic clearance of arterially infused ferromagnetic particles.

OBJECTIVE: Arterial embolization hyperthermia (AEH) consists of arterially embolizing tumours with ferromagnetic particles that generate hysteretic heating on exposure to an alternating magnetic field. It was the objective of this study to determine if such particles are cleared from the liver. METHOD: A lobe of normal liver in three pigs was arterially embolized with 300 mg of gamma-Fe2O3 particles (150 nm) suspended in lipiodol. The same liver lobe of three other pigs was embolized with 300 mg of ferromagnetic polymer matrix-encapsulated microspheres (32 microm) suspended in 1% tween-water. Samples of liver and blood were obtained before infusion, and at 60 min and 28 days after arterial infusion. At 28 days, samples of lung and other abdominal viscera were also obtained. The tissue samples were chemically analysed for iron content, and submitted to histopathological examination. RESULTS: There was no significant reduction in the hepatic iron concentration in either treatment group 28 days after infusion. Both types of particles illicited an immunogenic response and were extensively phagocytosed in the liver. The particle/lipiodol suspension caused extensive necrosis of liver, while the microsphere/tween-water suspension was well tolerated. Small amounts of both types of ferromagnetic particles embolized in the lungs, but there was no evidence of embolization into other organs. There were no haematological or biochemical changes and all subjects experienced uneventful 28-day survivals. CONCLUSION: This study has shown that, although arterially infused ferromagnetic particles were extensively phagocytosed, there was no significant hepatic clearance 28 days after infusion. It also determined that the suspension of 150 nm ferromagnetic particles in lipiodol was too vaso-occlusive for use in hepatic tissue. However, the suspension of 32 microm microspheres containing ferromagnetic particles in tween-water was safe and well tolerated.

Animals↗
PubMedDate not supplied

Intramedullary nailing versus plate fixation for unstable forearm fractures in children.

The purpose of this study was to compare the clinical and radiographic results of plate and screw fixation with intramedullary nailing for unstable fractures of the radius and ulna in children. We proposed that there was a statistically significant difference in the functional outcome and rate of complications between the two groups of patients. A retrospective analysis of 23 patients who were treated with plate-and-screw fixation and 18 who were treated with intramedullary nailing was performed. The average age was 10 years (range, 5-15). Indications for operative treatment included open fractures, irreducible fractures, and unstable fractures. Excellent results were obtained in 78% of patients in both groups at an average of 12 months after surgery. The functional results, rate of union, and rate of complications were statistically similar for the two groups. Intramedullary fixation allows short operative time, excellent cosmesis, minimal soft-tissue dissection, ease of hardware removal, and early motion after nail removal. Intramedullary fixation may provide a useful alternative for treatment of unstable fractures of the radius and ulna.

Adolescent↗