Transurethral hyperthermia for benign prostatic hyperplasia: Long term results

Transurethral resection of the prostate (TURP) is the only recognized treatment in patients with benign prostatic hyperplasia (BPH). Transurethral hyperthermia (TUHT) was used as an alternative treatment in patient who refused TURP. From 1987 to 1988, 21 BPH patients with moderate to severe symptoms and signs of prostatism were treated with TUHT in a phase I trial. Mean pre-treatment subjective and objective values were: Total symptom score (TSS) 13.5, obstructive symptom score (OSS) 6.5, irritative symptom score (TSS) 7.0, peak flow rate (PFR) 11.6 cc/sec, post-voiding residual volume (PRV) 187 cc, and prostate volume (PV) 93 cc. TUHT was given for a total of 177 sessions (mean 8.4), each of 60 min duration at a steady state. Temperature was recorded continuously on the urethral surface, in all treatments. It ranged from T_min 40.3d`C to T<sub>max</sub> = 49.2d`C and T_mean = 44.1d`C. The mean minimum temperature of ≥ 42d`C was obtained in 98% of the TUHT sessions. Treatments were given on an outpatient basis without sedation or anaesthesia. Treatment tolerance was excellent with minor acute toxicity common (71% of patients), of no clinical importance and with no late complications. Of the 21 patients treated, 17 (81%) had an objective and 15 (71%) a subjective improvement recorded at 6 months post-treatment. This statistically highly significant improvement included: 61% decrease in TSS; 66% decrease in OSS; 55% decrease in ISS; 42% increase in PFR; 55% decrease in PRV; and 21% decrease in PV. Of the 17 patients with objective improvement, nine have maintained their response to TUHT for a minimum period of over six years, two relapsed at 11 and 40 months, respectively, and six patients died of cardiovascular causes maintaining their response to death. This study has demonstrated TUHT treatment efficacy with no major or clinically important toxicity in BPH patients. A relative weakness of this report is a lack of verification of objective study parameters in the patients at seven years post-treatment. Prospective randomized trials are needed to define the role of TUHT in the management of BPH patients.     

Combination radiofrequency thermal ablation and adjuvant IV liposomal doxorubicin increases tissue coagulation and intratumoural drug accumulation

There has been marked interest in minimally-invasive, image-guided radiofrequency (RF) tumour ablation (i.e. coagulating tumour using short duration heating (<15?min) by directly applying temperatures >50°C via needle electrodes) to treat focal liver, renal, breast, bone and lung tumours. In spite of advances in RF technology and improved understanding of tumour biophysiology that now enable experimental treatment of tumours up to 5?cm, investigators have been unable to achieve complete ablation in many cases, particularly at the tumour margins and adjacent to blood vessels. One strategy for overcoming these limitations has been to take advantage of complementary interactions between RF thermal ablation and chemotherapy, particularly liposomal doxorubicin preparations, to attempt more complete tumour destruction. This paper will review published laboratory investigations demonstrating that this combined treatment paradigm has the unique potential both to potentiate preferential delivery of cytotoxic agents in liposome vehicles and to maximize the completeness of ablation of a treated tumour. New confirmatory data describing increased tumour destruction with RF ablation combined with different liposome preparations, documenting increased lipid peroxidation and expanding on previously published tumour growth studies is presented. Additionally, early clinical data including a randomized, pilot clinical study on 10 patients with primary and metastatic liver tumours, in which a non-optimized combination of RF ablation and IV liposomal doxorubicin (Doxil) increased the volume of tumour destruction 25–30% compared to RF alone, will also be described in detail.     

Increase of epidermal growth factor-stimulated cell-cycle progression and induction of thermotolerance by heat shock: Temperature and time relationship

When quiescent confluent cultures were incubated at increased temperature and then incubated at 37°C prior to a second increase of temperature (46°C) it appeared that heat-induced morphological alteration and ability to proliferate could be influenced by the previous thermal history of the cells. Incubations for 20 min in a temperature range of 41–46°C caused cells to develop thermotolerance within 3 h of incubation at 37°C.

Confluent quiescent Swiss mouse 3T3 cells were incubated at 41.8, 43.7 or 45.6°C and then reincubated at 37°C to determine the effects of heat shock on the mitogenic effects of epidermal growth factor (EGF). Preincubation at 43.7°C or 45.6°C enhanced stimulation of G₁-S progression by EGF. Preincubation at 43.7°C markedly increased the rate at which cells enter the S phase without changing the length of the lag phase. A comparison of the duration of incubation at 43.7°C for potentiation of EGF-induced DNA synthesis and that for induction of thermotolerance showed that a similar time interval for induction of effect could be implied.     

Phase I evaluation of hyperthermia equipment– University of Utah Institutional Report

At the University of Utah Medical Center the thrusts of the effort with respect to the NCI Hyperthermia Equipment Evaluation Contract have been threefold. The first objective was the development of a reliable thermometry system for collecting temperature information as a function of space as well as time. The second objective was the evaluation and comparison of a number of hyperthermia devices, particularly with respect to deep-heating devices, and specifically as pertains to the BSD annular phased array system (AA) and its various configurations. The third objective was to develop methodology for analysing hyperthermia data which could be easily adapted toward device comparison. In the period from 10/81-1/86, a total of 137 patients were treated with one or more of 10 devices, totalling 199 device evaluations at the University of Utah Medical Center or the subcontracting institution, LDS Hospital. Of these, 132 device evaluations involved deep-seated tumours. The AA was found to be feasible for deep pelvic regional hyperthermia, although the frequency of reversible acute toxicity was high, and achievement of desired temperatures was frequently limited by one of several factors. The radiative electromagnetic wave applicators which were evaluated for treatment of superficial tumours were found to be mostly feasible for tumours of the thoracic and extremities regions, although the heating patterns were frequently too shallow or too small in area, when compared with the size of the lesion.     

Thermotherapy in dermatology

Heat has been used as a medicinal and healing modality throughout human history. Today, thermotherapy is being studied in the treatment of many diseases. Although the exact anti-infective mechanism of thermotherapy is yet to be solved, this historically important healing method has shown significant results in the treatments of a variety of dermatological infectious diseases ranging from simple acne to bacterial, parasitic and viral infections, in modern medicine. Induction of cellular apoptosis in medium doses and necrosis in high doses has made thermotherapy an important modality in the treatment of malignant tumors. Especially in dermatology, significant results have been achieved in the treatment of Bowen’s disease, melanoma and simple warts. Thermotherapy, which today has also shown advancements in cosmetology, can be delivered by liquid nitrogen in the form of hypothermia and a variety of ways ranging from hot water pads to ultrasound and even to lasers, in the form of hyperthermia. In this article, the place of this historically important treatment method in modern medicine, especially in dermatology, has been reviewed by an extensive search of the literature.     

Tumour oxygenation is increased by hyperthermia at mild temperatures

The effects of hyperthermia on the oxygenation status in R3230 AC tumours of Fischer rats were measured using a polarographic oxygen electrode system. The median pO₂ in about 10mm diameter tumours grown s.c. in the leg of rats was 3·7 ± 0·3 mm Hg and it significantly increased upon heating at modest temperatures. For example, the tumour pO₂ measured within 10–15 min after heating for 30 min at 42·5°C was about three-fold greater than that in the control tumours. About 62% of pO₂ values measured in control tumours were < 5 mm Hg. After heating at 42·5°C for 30min, 37% of pO₂ values were < 5 mm Hg. Such an increase in tumour oxygenation or reoxygenation of hypoxic cells appeared to result from an increase in tumour blood flow caused by the mild temperature hyperthermia. The presence of hypoxic cells in tumours is believed to be a major factor in limiting the effectiveness of radiotherapy, certain chemotherapy drugs and phototherapy. Hyperthermia at mild temperatures easily achievable with the use of presently available clinical hyperthermia devices may be an effective means to overcome the hypoxic protection in the treatment of human tumours.     

Auditory brainstem response during systemic hyperthermia

The relationship between the brain temperature and the latency of ABR was evaluated in a dog model of systemic hyperthermia induced by heating of the blood during extracorporeal circulation. The latency of ABR was shortened and the amplitude was reduced with the elevation of brain temperature. The shortening of the latency was more notable in wave 4 than in wave1, and this is considered to have been due to greater changes in the conduction velocity in the central nervous system than in peripheral nerves. The latency of ABR, from which the brain temperature can be estimated, is considered to be clinically useful as an index of brain temperature during systemic hyperthermia.     

Design and analysis of annular antenna arrays with different reflectors

The design and performance of annular antenna arrays with reflectors is presented. Arrays with three shapes of reflectors are analysed and simulated. These include the corner reflector, the circular reflector and the elliptical reflector. Power-density distributions within the annular arrays with and without reflectors are obtained by using the FDTD method. Also, the image theory method is used to verify the FDTD results in one case. By comparing the power-density distribution pattern of all four of the array designs (three with different reflectors, one without reflector), it is readily seen in each case that the array with reflectors yields better power-efficiency than the array without reflectors and the elliptical reflector yields the best performance. Comparisons of each array are made using 4, 6 and 8 antennae in the annular array. By using the optimized results of the elliptical reflector, the requirement for the input-power level to each antenna is greatly reduced.     

I N M EMORY OF K EITH N EELY,P H D,MPA, EMT-P

Abstract

Objective. We compared the use of two active cooling devices with passive cooling in a moderate-temperature (≈22°C) environment on heart rate (HR) and core temperature (T_c) recovery when applied to firefighters following 20 minutes of fire suppression. Methods. Firefighters (23 men, two women) performed 20 minutes of fire suppression at a live-fire evolution. Immediately following the evolution, the subjects removed their thermal protective clothing and were randomized to receive forearm immersion (FI), ice water perfused cooling vest (CV), or passive (P) cooling in an air-conditioned medical trailer for 30 minutes. Heart rate and deep gastric temperature were monitored every 5 minutes during recovery. Results. A single 20-minute bout of fire suppression resulted in near-maximal mean ± standard deviation HR (175 ± 13 b·min^?1, P; 172 ± 20 b·min^?1, FI; 177 ± 12 b·min^?1, CV) when compared with baseline (p < 0.001), a rapid and substantial rise in T_c (38.2° ± 0.7°, P; 38.3° ± 0.4°, FI; 38.3° ± 0.3°, CV) compared with baseline (p < 0.001), and body mass lost from sweating of nearly 1 kilogram. Cooling rates (°C·min) differed (p = 0.036) by device, with FI (0.05 ± 0.04) providing higher rates than P (0.03 ± 0.02) or CV (0.03 ± 0.04), although differences over 30 minutes were small and recovery of body temperature was incomplete in all groups. Conclusions. During 30 minutes of recovery following a 20-minute bout of fire suppression in a training academy setting, there is a slightly higher cooling rate for FI and no apparent benefit to CV when compared with P cooling in a moderate temperature environment.