Biomedical subjects

Peter Wust

Publications and source records attributed to Peter Wust.

46 records · Page 3Linked to original sources

PubMed2004

Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation.

PURPOSE: To evaluate computed tomography (CT)-guided brachytherapy in patients with very large liver malignancies or with liver tumors located adjacent to the liver hilum. MATERIALS AND METHODS: In this prospective nonrandomized phase II trial, we treated 20 patients (19 liver metastases and one cholangiocarcinoma) with CT-guided high-dose-rate (HDR) brachytherapy using a (192) Iridium source. All patients demonstrated no functional liver degradation prior to irradiation. Entry criteria were liver tumors > 5 cm (group A, n = 11, no upper limit) or liver tumors < or = 5 cm adjacent to the liver hilum (group B, n = 9). Dose planning for brachytherapy was performed with three dimensional (3D) CT data acquired after percutaneous applicator positioning. Magnetic resonance (MR) imaging follow-up was performed 6 weeks and every 3 months post intervention. Primary endpoints were complications, local tumor control (absence of tumor growth after treatment followed by shrinkage of the lesion starting at 6 months) and progression-free survival. RESULTS: The mean tumor diameter was 7.7 cm (range, 5.5-10.8 cm) in group A, 3.6 cm (range, 2.2-4.9 cm) in group B. On average, a minimal dose of 17 Gy in the target volume was applied (range, 12-25 Gy). Severe side effects were recorded in two patients (10%). One patient demonstrated an obstructive jaundice caused by tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. One patient developed intra-abdominal hemorrhage that was treated by a single blood transfusion and has ceased. We frequently encountered moderate increases of liver enzymes (70% of patients) and bilirubin (50% of patients) without clinical symptoms and thus considered to be insignificant. The median follow-up was 13 months. In group A (tumors > 5 cm), primary local tumor control after 6 and 12 months was 74% and 40%, respectively; in group B, it was 100% and 71%, respectively. All but one local recurrence (in a patient with diffuse tumor progression) were successfully treated during another CT-guided brachytherapy leading to a primary assisted local control of 93% after 12 months. CONCLUSION: CT-guided brachytherapy based on individual dose plans and 3D CT data sets generated encouraging results in large liver malignancies as well as in tumors located adjacent to the liver hilum.

Adult↗

PubMed2004

Description and characterization of the novel hyperthermia- and thermoablation-system MFH 300F for clinical magnetic fluid hyperthermia.

Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep tissues by overcoming limitations of conventional heat treatments. After infiltration of the target tissue with nanosized magnetic particles, the power of an alternating magnetic field is transformed into heat. The combination of the 100 kHz magnetic field applicator MFH 300F and the magnetofluid (MF), which both are designed for medical use, is investigated with respect to its dosage recommendations and clinical applicability. We found a magnetic field strength of up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture height up to 300 mm. The specific absorption rate (SAR) can be controlled directly by the magnetic field strength during the treatment. The relationship between magnetic field strength and the iron normalized SAR (SAR(Fe)) is only slightly depending on the concentration of the MF and can be used for planning the target SAR. The achievable energy absorption rates of the MF distributed in the tissue is sufficient for either hyperthermia or thermoablation. The fluid has a visible contrast in therapeutic concentrations on a CT scanner and can be detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and practicability for heat treatment in deep regions of the human body.

Biophysical Phenomena↗

PubMed2003

Dynamic expression profile of p21WAF1/CIP1 and Ki-67 predicts survival in rectal carcinoma treated with preoperative radiochemotherapy.

PURPOSE: We investigated p53 and its downstream effectors p21WAF1/CIP1, BAX, and hMSH2 as well as the proliferation marker Ki-67 (mki-67/MIB-1) in patients undergoing preoperative radiochemotherapy for rectal carcinoma to identify prognostic and predictive factors. The focus of this study was on the dynamics of these genetic markers in a longitudinal study-that is, before and after radiochemotherapy. PATIENTS AND METHODS: Expression of p53, BAX, p21WAF1/CIP1, Ki-67, and hMSH2 was investigated by immunohistochemistry in pre- and posttherapeutic tumor samples in 66 patients. Tumor DNA was screened for p53 mutations by single-strand conformation polymorphism-polymerase chain reaction (SSCP-PCR). Paired tumor samples (pretherapy and posttherapy) were collected prospectively. RESULTS: Patients with a decrease in p21 expression following radiochemotherapy had better disease-free survival (P =.03). Similarly, patients with an increase in proliferative activity as measured by increased Ki-67 expression posttherapy had better disease-free survival (P <.005). In addition, we observed a significantly better prognosis for patients with high hMSH2 expression. In contrast, pretherapeutic levels of p53, BAX, or p21 expression and p53 mutation had no prognostic value, indicating that the combination of radiotherapy and chemotherapy might override defects in these genes. CONCLUSION: These findings are novel and support the clinical relevance of p21 in the suppression of both proliferation and apoptosis. Thus, the dynamic induction of p21WAF1/CIP1 was associated with a lower proliferative activity but an ultimately worse treatment outcome following neoadjuvant radiochemotherapy and tumor resection. Induction of p21, therefore, represents a novel resistance mechanism in rectal cancer undergoing preoperative radiochemotherapy.

Adult↗

PubMed2003

Clinical use of the hyperthermia treatment planning system HyperPlan to predict effectiveness and toxicity.

PURPOSE: The main aim is to prove the clinical practicability of the hyperthermia treatment planning system HyperPlan on a beta-test level. Data and observations obtained from clinical hyperthermia are compared with the numeric methods FE (finite element) and FDTD (finite difference time domain), respectively. METHODS AND MATERIALS: The planning system HyperPlan is built on top of the modular, object-oriented platform for visualization and model generation AMIRA. This system already contains powerful algorithms for image processing, geometric modeling, and three-dimensional graphics display. A number of hyperthermia-specific modules are provided, enabling the creation of three-dimensional tetrahedral patient models suitable for treatment planning. Two numeric methods, FE and FDTD, are implemented in HyperPlan for solving Maxwell's equations. Both methods base their calculations on segmented (contour based) CT or MR image data. A tetrahedral grid is generated from the segmented tissue boundaries, consisting of approximately 80,000 tetrahedrons per patient. The FE method necessitates, primarily, this tetrahedral grid for the calculation of the E-field. The FDTD method, on the other hand, calculates the E-field on a cubical grid, but also requires a tetrahedral grid for correction at electrical interfaces. In both methods, temperature distributions are calculated on the tetrahedral grid by solving the bioheat transfer equation with the FE method. Segmentation, grid generation, E-field, and temperature calculation can be carried out in clinical practice at an acceptable time expenditure of about 1-2 days. RESULTS: All 30 patients we analyzed with cervical, rectal, and prostate carcinoma exhibit a good correlation between the model calculations and the attained clinical data regarding acute toxicity (hot spots), prediction of easy-to-heat or difficult-to-heat patients, and the dependency on various other individual parameters. We could show sufficient agreement between the calculations and measurements for power density (specific absorption rate) within the range of assessed precision. Tumor temperatures can only be estimated, because of the rather variable perfusion conditions. The results of the FE and FDTD methods are comparable, although slight differences exist resulting from the differences in the underlying models. There are also statistically provable differences among the tumor entities regarding the attained specific absorption rate, temperatures, and volume loads in normal tissue. However, gross fluctuations exist from patient to patient. CONCLUSION: The hyperthermia planning system HyperPlan could be validated for a number of the 30 patients. Further improvements in the implemented models, FE and FDTD, are required. Even at its present state of development, hyperthermia planning for regional hyperthermia delivers valuable information, not only for clinical practice, but also for further technologic improvements.

Algorithms↗

PubMed2003

Whole body hyperthermia induces apoptosis in subpopulations of blood lymphocytes.

Whole Body Hyperthermia (WBH) has been shown to induce alterations of lymphocyte subpopulations in peripheral blood: T-cells decrease and NK-cells increase in number in the course of this therapy. As elevated temperature induces programmed cell death in healthy lymphocytes in vitro, we intended to determine the role of lymphocyte apoptosis in WBH by measuring the rate of apoptosis in blood lymphocytes in the course of this treatment. Blood was taken from cancer patients, treated with whole body hyperthermia and chemotherapy, before, during and the day after treatment. Apoptosis rates of the whole lymphocyte population, as well as, of B-, T-, CD4 + -T-, CD8 + -T-, and Natural-Killer (NK)-cell-subpopulations were determined by staining with AnnexinV-FITC and FACS flow analysis. A significant rise of apoptosis in the whole lymphocyte population, in CD4 + -T- and in CD8 + -T-cells occurred during treatment. In contrast, an elevated rate of apoptosis in NK-cells was observed 20 hours after termination of WBH. These differences were similar when the cells were incubated at 37 degrees C for 24 hours. Our results suggest, that apoptosis is one reason for the previously described decrease of T-cells during WBH and of NK-cells after WBH, and that the hyperthermia-related apoptosis-inducing mechanism is different in T-cells and NK-cells.

Adult↗

PubMed2003

Development and evaluation of a three-dimensional hyperthermia applicator with Water-COated Antennas (WACOA).

A novel twelve-channel three-dimensional (3-D) hyperthermia applicator has been developed and evaluated, which consists of twelve separate WAter COated Antenna (WACOA) modules. The modules are arranged in three transversal antenna rings (sub-arrays) and are placed into an acrylic applicator frame as cartridge-like elements in a staggered arrangement. The operating frequency is 100 MHz. For the design of the applicator, the finite-difference time-domain (FDTD) method was used. The applicator's dimensions allow its placement into the gantry of a magnetic resonance (MR) tomograph. The WACOA modules are designed as MR-compatible specially shaped metallic cylindrical dipole structures that are placed into hermetically closed water-filled cassettes. Due to the design of the dipole structures, only a conventional coaxial feed circuitry is needed, and no external impedance matching networks are necessary. Instead, fine on-line impedance matching is realized using adjustable tuning rods and matching rings, both elements being parts of the radiating antenna structure. Experimental and numerical evaluations demonstrate a good stability of impedance matching, a low inter-channel coupling of less than -20 dB, and a good ability of field pattern steering.

Algorithms↗

PubMed2002

Restaging of locally advanced carcinoma of the rectum with MR imaging after preoperative radio-chemotherapy plus regional hyperthermia.

BACKGROUND: The restaging accuracy of MR imaging in advanced primary rectal carcinoma after preoperative radiochemotherapy and regional hyperthermia was evaluated and compared with the histopathologically verified degree of tumor remission after a course of radio-chemo-thermotherapy. PATIENTS AND METHODS: 35 patients with primary rectal carcinoma (uT3/uT4) underwent MRI using a surface coil 4-6 weeks after radiochemotherapy (n = 35), regional hyperthermia (n = 23), and before curative surgery. We defined as gold standard for the remission status the comparison of pretherapeutic endosonography with the histopathology of the resected specimen. RESULTS: T category was correctly restaged after preoperative treatment in only 19 (54%) of 35 patients. Nine of 20 responders were overstaged and seven of 15 non-responders were understaged. Concurrently, the N category was correctly restaged in 19 (54%) of 35 patients (twelve responders and seven non-responders). Overstaging occurred in four responders and two non-responders, understaging occurred in four responders and six non-responders. CONCLUSIONS: MRI proved independent of the response status as not suitable to restage locally advanced rectal carcinoma after preoperative radiochemotherapy despite optimized imaging technique and spatial resolution. Basically, imaging the morphology of a tumor cannot clearly differentiate between vital and devitalized tissue after a treatment. Functional imaging such as PET (positron emission tomography) appears more feasible for restaging after radio-chemo-thermotherapy.

Adult↗

PubMed2002

The cellular and molecular basis of hyperthermia.

In oncology, the term 'hyperthermia' refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial hyperthermia, hyperthermic chemoperfusion, and whole-body hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by hyperthermia.

Cell Death↗

PubMed2002

Experimental and numerical investigation of feed-point parameters in a 3-D hyperthermia applicator using different FDTD models of feed networks.

Experimental and numerical methods were used to determine the coupling of energy in a multichannel three-dimensional hyperthermia applicator (SIGMA-Eye), consisting of 12 short dipole antenna pairs with stubs for impedance matching. The relationship between the amplitudes and phases of the forward waves from the amplifiers, to the resulting amplitudes and phases at the antenna feed-points was determined in terms of interaction matrices. Three measuring methods were used: 1) a differential probe soldered directly at the antenna feed-points; 2) an E-field sensor placed near the feed-points; and 3) measurements were made at the outputs of the amplifier. The measured data were compared with finite-difference time-domain (FDTD) calculations made with three different models. The first model assumes that single antennas are fed independently. The second model simulates antenna pairs connected to the transmission lines. The measured data correlate best with the latter FDTD model, resulting in an improvement of more than 20% and 20 degrees (average difference in amplitudes and phases) when compared with the two simpler FDTD models.

Computer Simulation↗

PubMedDate not supplied

Radiation exposure to patient and staff in hepatic chemoembolization: risk estimation of cancer and deterministic effects.

The purpose of the study was to determine the risks of radiation-induced cancer and deterministic effects for the patient and staff in transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). Sixty-five patients with HCC underwent the first cycle of TACE. Thermoluminescence dosemeters and conversion factors were used to measure surface doses and to calculate organ doses and effective dose. For the patient, the risk of fatal cancer and severe genetic defect was in the magnitude of 10(-4) and 10(-5), respectively. Five patients showed surface doses over the first lumbar vertebra exceeding 2000 mSv and 45 patients showed doses over the spine or the liver region above 500 mSv. The risk of fatal cancer and severe genetic defect for the radiologist and assistant was in the magnitude of 10(-7) to 10(-8). They could exceed the threshold for lens opacity in the case of more than 490 and 1613 TACE yearly for a period of many years, respectively. Radiation dose could lead to local transient erythema and/or local depression of hematopoiesis in many patients after TACE. For the radiologist and assistant, risk of fatal cancer and genetic defect and lens opacity might arise when they perform interventions such as TACE intensively.

Adult↗