Comparison of serum 25(OH) vitamin D, parathormone and immunity marker concentrations between dogs with transmissible venereal tumour and healthy dogs.

BACKGROUND: 1,25-Dihydroxyvitamin D (1,25(OH)2 D) is vital in the homeostasis of calcium and bone health as well as in the prevention of many disorders such as neoplasms. Epidemiological data show that low concentrations of both 1,25(OH)2 D and its precursor 25(OH) vitamin D (25(OH)D) are associated with an increased risk of a variety of human tumours. OBJECTIVES: To investigate 25(OH)D, parathormone (PTH) and immunity marker concentrations in dogs with transmissible venereal tumour (TVT). METHODS: 25(OH)D, PTH and various biochemical and immunity markers were evaluated in dogs with TVT (n = 26) and in healthy (n = 30) dogs. RESULTS: 25(OH)D concentrations were significantly lower in dogs with TVT in comparison with healthy dogs. In contrast, PTH, immunoglobulin G and interleukin (IL)-9 concentrations were higher in the dogs with TVT. Other variables, including IL-10, interferon γ, calcium and inorganic phosphate, were not statistically different between the two groups. CONCLUSIONS: Decreased serum 25(OH)D concentration may be a risk factor for the development of canine TVT; however, cause-and-effect remains incompletely understood. Further studies are required to elucidate the exact role of 25(OH)D in canine TVT and whether vitamin D supplementation may be useful prophylactically or as an adjunct to chemotherapy.

An inverse problem approach to recovery of in vivo nanoparticle concentrations from thermal image monitoring of MR-guided laser induced thermal therapy.

Quantification of local variations in the optical properties of tumor tissue introduced by the presence of gold-silica nanoparticles (NP) presents significant opportunities in monitoring and control of NP-mediated laser induced thermal therapy (LITT) procedures. Finite element methods of inverse parameter recovery constrained by a Pennes bioheat transfer model were applied to estimate the optical parameters. Magnetic resonance temperature imaging (MRTI) acquired during a NP-mediated LITT of a canine transmissible venereal tumor in brain was used in the presented statistical inverse problem formulation. The maximum likelihood (ML) value of the optical parameters illustrated a marked change in the periphery of the tumor corresponding with the expected location of NP and area of selective heating observed on MRTI. Parameter recovery information became increasingly difficult to infer in distal regions of tissue where photon fluence had been significantly attenuated. Finite element temperature predictions using the ML parameter values obtained from the solution of the inverse problem are able to reproduce the NP selective heating within 5 °C of measured MRTI estimations along selected temperature profiles. Results indicate the ML solution found is able to sufficiently reproduce the selectivity of the NP mediated laser induced heating and therefore the ML solution is likely to return useful optical parameters within the region of significant laser fluence.

Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model.

PURPOSE: To determine the effect of surrounding tissue type on coagulation necrosis from radiofrequency (RF) ablation in a homogeneous animal tumor model. MATERIALS AND METHODS: Thirty canine venereal sarcomas were implanted in three tissue sites (subcutaneous, kidney, and lung) in 13 mildly immunosuppressed dogs. Five of 25 tumors, which were 19 mm +/- 3 (mean +/- SD) in diameter, were allocated to each of five groups: (a) subcutaneous tumors, (b) kidney tumors, (c) lung tumors with blood flow, and (d) subcutaneous and (e) renal tumors without blood flow, which was achieved by sacrificing the animal to eliminate tumor perfusion. A sixth group comprised larger subcutaneous tumors (mean diameter, 46 mm +/- 4) that were also treated. RF ablation was performed with a 1-cm tip and 5 minutes of ablation at 90 degrees C +/- 1. Impedance, temperature, and resultant coagulation diameter were recorded and compared. Data were analyzed statistically, including one-way analysis of variance to determine the effect of tissue conductivity (ie, systemic impedance) on necrosis size and tissue temperatures. Linear regression analysis was used to compare changes in impedance between the control and experimental groups. RESULTS: Increasing linear correlation was observed between tumor coagulation diameter and overall baseline system impedance (R(2) = 0.65). RF ablation of lung tumors resulted in the greatest coagulation diameter (13.0 mm +/- 3.5) compared with that in the other groups (P <.01). The smallest coagulation diameter was observed in kidney tumors in the presence of blood flow (7.3 mm +/- 0.6) compared with that in the other groups (P <.01). Elimination of blood flow in kidney tumors increased coagulation diameter to 10.3 mm +/- 0.6 (P <.01). After RF ablation, coagulation diameter in the subcutaneous tumor groups was the same (mean, 9.8 mm +/- 1.0) (difference not significant), regardless of tumor size or presence of blood flow. CONCLUSION: The characteristics of tissue that surrounds tumor, including vascularity and electric conductivity, affect ablation outcome. Predominance of tissue-specific characteristics will likely result in site-specific differences in RF-induced coagulation necrosis.

Technical developments for cerebral thermal treatment: water-cooled diffusing laser fibre tips and temperature-sensitive MRI using intersecting image planes.

The aim was to determine if water-cooled diffusing tips could produce larger and safer (better controlled) thermal lesions than non-cooled diffusing tips at 980 nm. Thermal lesions were induced in beef myocardium in vitro with and without water cooling using a 980 nm diode laser at various power levels. Seven intracerebral treatments were performed in six canines using water-cooled diffusing tips with four animals having intracerebral transmissible venereal tumours grown from inoculate. Magnetic resonance thermal imaging (MRTI)-based feedback software using a fast, radio frequency-spoiled gradient echo acquisition with two intersecting image planes was used for on-line monitoring and control of treatment and for the evaluation of in vivo laser lesion production. In cases where two-plane MRTI was employed, the maximum calculated temperature was compared in each plane. Using water-cooled tips and 400 micro m core diameter laser diffusing fibres in in vitro beef myocardium, power of up to 9.5 W was applied for 8 min without tip failure. Without cooling, tip failure occurred in under 4 min at 6 W, in under 2 min at 7 W and instantaneously at 8 W. Additionally, char accompanied lesions made with uncooled tips while cooled application resulted in only minimal char at only the highest thermal dose. Achieved lesion cross-sectional diameters in in vitro samples were up to 26.5 x 23.3 mm when water cooling was used. In canine brain and transmissible venereal tumours, up to 18.1 x 21.4 mm lesions were achieved. It is concluded that water cooling allows safe application of higher power to small core diameter diffusing tip fibres, which results in larger thermal lesions than can be achieved without cooling. Two-plane MRTI enhances on-line monitoring and feedback of thermal treatment.

Ferromagnetic thermoseeds: suitable for an afterloading interstitial implant.

Previous studies have shown implantable ferromagnetic thermoseeds to be a promising hyperthermia method. However, migration from the implant site and chemical toxicity caused by corrosion of the thermoseed alloy have proven to be potential hazards. These problems could be overcome by placing the thermoseeds into removable catheters similar to those used for afterloading interstitial brachytherapy. As an additional merit, the method would allow convenient combination of heat and radiation therapy. To test the clinical performance of this method, we compared temperature distributions and biologic effects in canine muscle and transmissible venereal tumors for bare thermoseeds and thermoseeds contained within catheters. We found no significant difference in the heating patterns and similar tissue changes when all implants were removed immediately after heating. More severe tissue changes were present around bare thermoseeds that were retained. This suggests that catheters provide a safe and reliable method for thermoseed hyperthermia which would allow convenient combination with interstitial radiation.

Results of a preliminary study of the potential of vasodilators for improving thermotherapy of deep-seated tumours [printed with original paging at end of 2(2); omitted from Int J Hyperthermia 1986 Jan-Mar;2(1)].

Administration of the vasodilator hydralazine to a single mongrel dog with a transplanted, superficial transmissible venereal tumour in the abdomen permitted tumour-adjacent normal tissue temperature differences produced in local hyperthermia to be enhanced by nearly 2 degrees C. A preliminary study of tumour and normal tissue perfusion rate in the dog, employing the 15O-labelled water-positron emission tomography technique, suggested that administration of the vasodilator led to a significant reduction in the tumour perfusion rate, consistent with the observed tumour temperature enhancement. Computational studies with a multi-layer, one-dimensional cylindrical model of deep-tumour heating suggest that vasodilator-induced reductions of tumour perfusion rates could significantly increase deep tumour-superficial normal tissue temperature differences produced in deep-tumour thermotherapy.

Hyperthermia-induced vascular injury in normal and neoplastic tissue.

The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 degrees C and 45 degrees C for 20 minutes), were studied by histologic and ultrastructural examination. Normal muscle and Walker 256 tumors showed edema, congestion, and hemorrhage at 5 minutes post-heating (PH), followed by suppuration, macrophage infiltration, and thrombosis at 6 and 48 hours PH, and finally by regeneration and repair by 7 days PH. Vascular endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive injury occurred for at least 48 hours PH. Two hyperthermia treatments separated by a 30- or 60-min cooling interval, were applied to Walker 256 tumors in a subsequent study. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral steady state temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results suggest that vascular damage contributes to the immediate and latent cytotoxic effects of hyperthermia in normal tissue and some types of neoplastic tissue, and that selective heating of neoplastic tissue occurs in tumor tissue with disrupted microvasculature.

Hydralazine-enhanced selective heating of transmissible venereal tumor implants in dogs.

This study was designed to test the hypothesis that vasodilator drugs can enhance selective heating of solid tumors by producing a favorable redistribution of blood flow between tumor and normal tissues. Subcutaneous transmissible venereal tumor implants were heated by inductive diathermy using Helmholtz coils in 8 dogs. The temperature rise in tumor and adjacent muscle was measured before and after giving hydralazine (0.5 mg/kg i.v.). Blood flow to the tumors and underlying muscle was measured with radioactive tracer microspheres. Before hydralazine treatment mean muscle blood flow was about one-third tumor blood flow (0.11 +/- 0.02 vs 0.28 +/- 0.09 ml/min/g), and tumor and normal muscle temperatures were not significantly different (40.0 +/- 0.6 vs 39.7 +/- 0.1 degrees C). After hydralazine tumor blood flow decreased and muscle blood flow increased in every dog, and selective heating of the tumors became possible. Muscle blood flow averaged 0.67 +/- 0.13 ml/min/g, 17 times greater than tumor blood flow, which decreased to 0.04 +/- 0.02 ml/min/g. Core tumor temperature was 48.0 +/- 0.9 vs 38.5 +/- 0.5 degrees C for underlying muscle. Blood pressure was maintained at 80 +/- 5.7 mmHg. These results demonstrate that adjuvant treatment with vasodilators is a promising technique to increase the temperature difference between tumors and surrounding normal tissues during local heat therapy.