ABSTRACT
PURPOSE: To quantify the cooling effect of hepatic vessels on liver radiofrequency (RF) ablation ex situ. METHODS: Bipolar RF applicators (diameter = 1.8 mm, electrode length = 30 mm) were inserted parallel to perfused glass tubes (diameter = 5 and 10 mm; flow = 250-1,800 ml/min) at distances of 5 and 10 mm in porcine livers ex vivo. RF ablation was performed at 30 W/15 kJ. RF lesions were analyzed by measuring the maximum (r (max)) and minimum radius (r (min)) and the lesion area. RESULTS: Glass tubes without flow showed no influence on RF lesions, whereas perfused glass tubes had a significant cooling effect on lesions. r (min) was reduced to 50% at 5 mm applicator-to-vessel distance and the lesion area was reduced from 407 to 321 mm(2) (p < 0.001). There was no significant influence of glass tube diameter or flow volume on any of the analyzed parameters. CONCLUSIONS: Cooling effects of intrahepatic vessels could be simulated in an ex situ model. Cooling effects should be taken into account in RF ablation within 10 mm distance to major liver vessels regardless of blood flow volume or vessel diameter. Surgical RF ablation with temporary blood flow occlusion should be considered in such constellations.
Subject(s)
Catheter Ablation , Cold Temperature , Liver/blood supply , Animals , In Vitro Techniques , Statistics, Nonparametric , SwineABSTRACT
PURPOSE: To assess the effect of laser-induced thermotherapy (LITT) on liver metastases of various size from colon carcinoma in an animal model. MATERIALS AND METHODS: Liver metastases were implanted in 20 Wistar Albino Glaxo (WAG) rats by subcapsular injection of cells from a colorectal strain (CC531) (day 0). The animals were divided into two groups with regard to the measured tumor size of 0.05 - 0.06 cm (3) (group A) and 0.10 - 0.12 cm (3) (group B). On day 14 after laparotomy, the tumors were exposed to 1064 nm Nd:YAG laser light at 2 watts for 5 minutes after intratumoral placement of the laser applicator set. The tumor volumes before (V1, at day 13) and after treatment (V2, at day 28) were determined by MRI and the mean tumor growth ratio (V2/V1) was calculated. RESULTS: The mean tumor volumes V1 and V2 were 0.05 +/- 0.003 cm (3) and 0.23 +/- 0.016 cm (3) in group A, and 0.11 +/- 0.006 cm (3) and 0.68 +/- 0.037 cm (3) in group B. The mean tumor growth ratio (V2/V1) was 4.31 +/- 0.19 in group A and 6.11 +/- 0.14 in group B. The mean volume of the induced necrosis (0.15 +/- 0.01 cm (3)) was the same for both groups ( p > 0.05). Compared to group B, liver metastases of group A showed a significant slower tumor growth velocity (paired t-test, p < 0.0001). CONCLUSION: The interventional treatment of large hepatic tumors with LITT leads to faster tumor growth compared to smaller lesions.
Subject(s)
Hyperthermia, Induced/methods , Laser Therapy , Liver Neoplasms, Experimental/diagnosis , Liver Neoplasms, Experimental/therapy , Magnetic Resonance Imaging , Animals , Colonic Neoplasms , Liver Neoplasms, Experimental/secondary , Rats , Rats, Wistar , Time FactorsABSTRACT
The laser is a well established surgical instrument in lung therapy. This report provides information on the biophysical basics of the laser-induced thermotherapy (LITT) of lung metastases. Optical properties like absorption and scattering determine the penetration depth of laser radiation in tissue. These parameters vary dynamically during the application and define in combination with thermal tissue properties the achievable destruction volume. Parenchyma behaves very differently compared to more dense tissues due to local inhomogenities and the large amount cavaties filled with air. Beside an account of the affecting parameters an overview of therapy options is given. Therapeutic results depend not only on the tissue properties but also on the technical equipment, e.g. the applicator design and the energy applied. Complex dosimetric models allow for a calculation of the lesion's size in advance.
Subject(s)
Hyperthermia, Induced/methods , Laser Therapy , Lung Neoplasms/secondary , Minimally Invasive Surgical Procedures/methods , Animals , Biophysical Phenomena , Biophysics , Humans , Lung/pathology , Lung/surgery , Lung Neoplasms/surgery , Refractometry , Temperature , Treatment OutcomeABSTRACT
PURPOSE: To evaluate experimentally and clinically an internally cooled power laser system for percutaneous treatment of liver metastases, with magnetic resonance (MR) imaging guidance, to increase the volume of coagulative necrosis with single laser beam applications. MATERIALS AND METHODS: The power laser system consisted of standard cannulation paraphernalia and a specially designed 7-F protective catheter for cooling the laser tip during treatment to avoid carbonization. A microdome laser beam applicator with a laser tip diameter of 0.95 mm kept the entire device as small as possible. After the unit was tested in 40 porcine livers, 532 laser beam applications (mean power, 27.5 W [range, 22.1-30.0 W]; mean application time, 19.8 minutes [range, 14-30 minutes]) were performed with MR guidance in 127 patients with 318 liver metastases. The safety of the procedure and the volume of induced necrosis were evaluated. RESULTS: In vitro, cuboid areas of coagulative necrosis with a mean greatest diameter of 4.3 cm +/- 0.5 (SD) were demonstrated after single applications. In vivo, MR thermometry allowed accurate demarcation of changes induced by heat, with a mean diameter of necrosis of 3.3 cm +/- 1.4. No carbonization or vaporization of tissue or damage of equipment occurred during treatment. CONCLUSION: This power laser system can increase the volume of laser-induced necrosis in liver metastases with a single application, thereby simplifying and accelerating the treatment of larger lesions.
Subject(s)
Laser Coagulation/instrumentation , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Animals , Breast Neoplasms/pathology , Colorectal Neoplasms/pathology , Equipment Design , Female , Humans , Laser Coagulation/methods , Liver/surgery , Magnetic Resonance Imaging , Male , Middle Aged , SwineABSTRACT
Parathyroid hormone-related protein (PTHrP) plays a major role in the pathogenesis of humoral hypercalcemia of malignancy. It interacts with the PTH receptor and has therefore a nearly identical effect on bone cells as PTH. However, PTHrP is thought to be less potent than PTH in stimulating adenylate cyclase in canine renal membranes, leading to the hypothesis of a differential efficiency in signal transduction by PTHrP with respect to bone vs kidney. In a homologous model with intact osteoblast-like cells (UMR 106) and primary kidney cells, both from the rat, we have tested N-terminal peptide fragments, based on the rat amino acid sequence 1-34, of PTH and PTHrP. Compared with PTHrP(1-34), rat PTH(1-34) had a similar relative potency in bone cells (85%) and in kidney cells (140%) in its ability to stimulate adenylate cyclase. Human PTH(1-34) was 5.6- to 6.5-fold less potent than rat PTH(1-34) in both cell types. In human osteoblast-like cells (SaOS-2), rat and human PTH were essentially equally potent compared to PTHrP(1-34) (identical sequence in rat and human) in stimulating cAMP accumulation. In conclusion, our study revealed the equipotency of rat PTH(1-34) and PTHrP(1-34) in stimulating intracellular cAMP formation in a homologous system of rat bone and kidney cells. There seemed to be no unique signal transduction mechanism of PTHrP to the adenylate cyclase in rat kidney cells compared with bone cells.
Subject(s)
Antihypertensive Agents/pharmacology , Bone and Bones/metabolism , Cyclic AMP/biosynthesis , Kidney/metabolism , Parathyroid Hormone-Related Protein , Parathyroid Hormone/pharmacology , Peptide Fragments/pharmacology , Proteins/pharmacology , Adenylyl Cyclases/metabolism , Animals , Bone and Bones/cytology , Cell Line , Humans , Kidney/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Rats , Recombinant Proteins/pharmacology , TeriparatideABSTRACT
Tumor necrosis factor alpha (TNF alpha) and parathyroid hormone-related protein (PTHrP) are both factors that have been implicated in the mechanism of hypercalcemia of malignancy. In this study we investigated the effect of TNF alpha on the PTHrP-stimulated accumulation of intracellular cyclic AMP in osteoblast-like cells. In the clonal cell line Saos-2 and in primary cell cultures from fetal rat calvaria, PTHrP-stimulated accumulation of cAMP was time- and dose-dependently inhibited by exposure to TNF alpha. Significant inhibition occurred at concentrations as low as 2 x 10(-12) M and was maximal at 1 x 10(-9) M. Inhibition was observed after 6 h and was maximal after 18 h. Inhibition by TNF alpha was probably mediated by protein kinase C, since the phorbol ester PMA mimicked the effect of TNF alpha, and the protein kinase C inhibitor H-7 completely abolished the effect of TNF alpha. In conclusion, these observations suggest a possible mechanism by which TNF alpha may modulate the effect of PTHrP on osteoblast function in the syndrome of humoral hypercalcemia of malignancy.