Local Microwave Hyperthermia Research Articles

Enhancement of ACNU treatment of the BT4an rat glioma by local brain hyperthermia and intra-arterial drug administration

To evaluate the role of intra-arterial (i.a.) chemotherapy, intravenous (i.v.) chemotherapy, and local brain hyperthermia in the treatment of gliomas, the effect of i.v. versus i.a. drug delivery, with or without local brain hyperthermia, was evaluated in BD IX rats with BT4An gliomas implanted in the right frontal lobe. The rats were given ACNU 18 mg/kg i.a. in the right carotid artery or i.v. in the inferior cava with or without local microwave hyperthermia at 42.4 degrees C for 45 min. ACNU i.v. alone had no notable effect on survival. Survival was prolonged when ACNU without hyperthermia was given i.a. instead of i.v. (P < 0.05). Thermochemotherapy with ACNU i.a. was more effective than with ACNU i.v. (P < 0.01). Survival improved as hyperthermia enhanced the i.v. drug effect (P < 0.01), and hyperthermia also improved the i.a. ACNU effect (P < 0.01). Post-treatment survival was more than doubled for the group given combined i.a. ACNU and hyperthermia, compared to controls. Thermochemotherapy, particularly with i.a. drug administration, seems to be a promising new approach for the treatment of primary brain tumours. However, more knowledge about tolerance of human brain tissue to hyperthermia is necessary before this treatment modality is used in patients with a reasonable life expectancy.

Original Articles: Bladder Cancer: A New Approach Using Local Combined Microwave Hyperthermia and Chemotherapy in Superficial Transitional Bladder Carcinoma Treatment

For some time hyperthermia, alone or in combination with radiotherapy or chemotherapy, has proved to be a promising method for treating several kinds of solid tumors. After intensive laboratory investigations a new device, based on a microwave source delivering local bladder hyperthermia together with intravesical mitomycin C chemotherapy has been clinically tested as a neoadjuvant approach in 44 patients suffering from superficial cancer of the bladder. The combined approach was administered on an outpatient basis without major complications and with acceptable local toxicity. Endoscopic and histological evaluations proved that combined local hyperthermia and chemotherapy can induce necrosis of transitional tumors. The overall response rate was 90.8%, with 70.4% complete and 20.4% partial, leaving 4 patients (9.2%) nonrespondent. Clinical and histological evaluations have confirmed the feasibility and safety of this combined treatment. Further multicentric studies have been initiated.

悪性黒色腫の電子線治療 電子線照射により除痛と進行抑制できた悪性黒色腫の２例

We reported two cases of malignant melanoma with multiple metastases who were satisfactorily treated with electron irradiation in reducing pain of bone metastases or improving disabling nervous symptoms respectively.Case 1: A 40-year-old woman who had underwent wide local excision of a pigment macule on the left sole following three courses of chemotherapy (DAV) under the diagnosis of multiple metastases of malignant melanoma was referred to us in September, 1993. On admission, she received combination chemotherapy with ranimustine, vincristine and peplomycin which failed to prevent the metastases. For the reduction of the pain and prevention of fracture of bone metastases, electron irradiation in combination with local microwave hyperthermia was performed. The schedule was 6 Gy a time, twice a week to the total of 36 Gy on each irradiation site. Although the patient died of brain metastases in February, 1995, the effect on the pain was remarkable. Oral morphine HCl could be reduced and withdrawn during irradiation.Case 2: A 67-year-old man was admitted for his primary melanoma nodule on the left sole and lymph node metastases on the left groin in December, 1993. After wide local excision and lymph node dissection, he was treated with systemic chemotherapy (5 courses of DAV) and local IFN-β injection on secondary skin metastases without satisfactory effect. Cisplatin was also ineffective for hemiplegia, hemianopia and agnosia which developed in July, 1994. Whole and local brain electron irradiation of total 37.8 Gy improved hemiplegia and hemianopia. Metastatic image on brain CT was reduced. Irradiation was obliged to stop for leukopenia and the patient died in February, 1995.Although radiotherapy is not the first choice for malignant melanoma, especially multiple metastases so far, even low LET beam, such as electron beam, is thought to be useful clinically from our experiences.

Suppression of murine melanoma growth with a combination of microwave hyperthermia and local injection of interleukin 2.

Local microwave hyperthermia in combination with local injections of interleukin 2 (IL-2) was found to exert a remarkable suppressive effect on murine melanoma growth. Both of these therapeutic modalities caused marked tumour infiltration with natural killer cells. After microwave hyperthermia or IL-2 injection alone there was minimal T-cell infiltration, but T cells were more in evidence following combination therapy.

Intensive preoperative radiotherapy with local hyperthermia for the treatment of gastric carcinoma

In order to devitalize maximally tumour tissue and improve the prognosis of gastric cancer patients, a method employing preoperative intensive radiotherapy with local hyperthermia as adjuvant treatment was evaluated. In order to estimate the effectiveness of preoperative intensive radiation and radiation with local microwave hyperthermia in radical gastric cancer treatment, 293 patients were randomized into three respective treatment groups: surgery alone, surgery preceded by preoperative radiation; and surgery followed by preoperative radiation and hyperthermia. Preoperative radiation therapy to a total dose of 20 Gy in four 5 Gy fractions did not improve 3-or 5-year survival in gastric cancer patients in comparison with surgery alone. Local hyperthermia in combination with radiation therapy followed by surgery produced a significant improvement in 3-year survival of 22.1% (from 35.5 ± 4.9% to 57.6 ± 6.3%, P < 0.05) and 5-year survival of 21.3% (from 30.1 ± 4.7 to 51.4 ± 6.6%, P < 0.05). In unresectable gastric cancer patients, radiation therapy and radiation therapy with hyperthermia both increase mean survival. In conclusion; intensive preoperative radiation therapy in total dose 20 Gy plus local microwave hyperthermia significantly improved 3- and 5-year survival in comparison with surgery alone. Further development and evaluation of equipment to produce reliable and safe delivery systems for hyperthermia is needed.

A combined therapeutic modality with hyperthermia and locally administered rIFN-β inhibited the growth of B16 melanoma in association with the modulation of cellular infiltrates

Murine B16-F10 melanoma was treated with local microwave hyperthermia, local injection of murine recombinant interferon-beta (rIFN-β) or a combination of both in order to investigate the augmentation of anti-proliferative effects with this combination treatment. Concerning the local modulation of immunological reactions of the host, local hyperthermia at 43°C for 15 min on murine melanoma caused remarkable infiltration of natural killer cells and local injection of rIFN-β led to considerable infiltration of T cells. When these two modalities were combined, the infiltration of NK cells completely disappeared and, instead, remarkable augmentation of T cell infiltration occurred. Synergistic suppressive effects on melanoma growth with occasional scar formation were seen with this combined modality. These results indicate that local hyperthermia with a combination of rIFN-β modulates local immune reactions of the host, and probably this immune reaction is partly involved in the course of the suppression of tumor growth.

Cisplatin, hyperthermia, and radiation (trimodal therapy) in patients with locally advanced head and neck tumors: A phase I–II study

Purpose : Hyperthermia is now being widely used to treat clinical malignancies especially combined with radiotherapy and more rarely with chemotherapy. The combination of heat, radiation, and chemotherapy (trimodality) can lead to potent interaction. The present Phase I–II study was conducted to evaluate the feasibility and acute toxicity of a combination of cisplatin, hyperthermia, and irradiation in the treatment of superficial cervical nodal metastases from head and neck cancer. Methods and Materials : Eighteen patients with measurable neck metastases from previously untreated squamous cell head and neck tumors were entered into the trial. Therapy consisted of a conventional irradiation (total dose 70 Gy, 2 Gy five times a week) combined with a weekly administration of 20 mg/m 2 iv of cisplatin and a total of two sessions of local external microwave hyperthermia (desired temperature of 42.5°C for 30 min). Results : Feasibility of the treatment was demonstrated. Acute local toxicity was mild; no thermal blisters or ulcerations were reported and only two patients experienced local pain during hyperthermia. Cutaneous toxicity appeared greater than in our previous studies with irradiation plus hyperthermia and irradiation plus cisplatin. Systemic toxicity was moderate with major toxic effects observed in three patients (World Health Organization (WHO) grade 3 anaemia). Even though it was not an aim of the study to evaluate the nodal response, we observed a complete response rate of 72.2% (95% confidence interval 51–93.4%), 16.6% of partial response and 11.1% of no change. Conclusion : The study confirms the feasibility of the combination of cisplatin, heat, and radiation with an acceptable toxicity profile. The trimodal therapy deserves further evaluation as a way to enhance the efficacy of irradiation in the treatment of nodal metastases from head and neck tumors.

Temperature mapping in the canine prostate during transurethrally-applied local microwave hyperthermia.

Although the therapeutic effects of heat on tumors have been known for more than a century, only recently has hyperthermia been applied in the treatment of various solid tumors in a scientific fashion. In preliminary clinical trials, heat applied by transurethrally or transrectally placed microwave antennas has been used in the treatment of benign prostatic hyperplasia (BPH) with some success. However, basic information about prostatic temperature distribution and the cellular effects of hyperthermia is lacking. In an attempt to establish the safety of local hyperthermia of the prostate and the precise temperature distribution within the gland, we performed temperature mapping studies in canine prostates. Eight mongrel dogs were anesthetized, and a 16 Fr catheter with three helical coil microwave antennas was placed in the bladder through a perineal urethrostomy. Laparotomy was performed and the bladder opened. The antennas were placed under direct control in the prostatic urethra. Linear array and single point thermometers (Clini-Therm TS1200 thermometry system) were placed (1) within the catheter alongside the antennas, (2) alongside the Foley catheter in the urethra, and (3) longitudinally and radially in the prostate for mapping of tissue temperature. Heating was performed with a 915-MHz ISM frequency Z-80 microprocessor controlled microwave power generator (Prostek 3000, Clini-Therm Corporation, Dallas, TX) using 2-9 watts per channel (6-27 watts total) for 30 min to 1 hr. Baseline body temperatures varied between the individual dogs from 37 degrees to 38 degrees C, but temperature distribution within the prostate was even prior to heating. With relatively low power (6 watts total), temperatures of greater than or equal to 45 degrees C were reached within the catheter. Therapeutic temperatures of approximately 43 degrees C were achieved in the periurethral prostate. Intraurethral temperatures were in general 1-2 degrees C lower than within the catheter. The radial temperature dropoff in the prostate was sharp and about 1 degrees C per 3-mm distance from the catheter. This would limit the area of effectiveness to a periurethral zone of 1 cm in diameter in this model. No unsafe temperature peaks were noted either intraurethrally or between the prostate and the rectum during steady-state conditions. Histologic studies demonstrated an intact rectal wall and varying degrees of prostatic inflammation and/or necrosis despite uniform treatment regimens administered. These studies demonstrate the short-term safety of microwave hyperthermia in the canine prostate. Further studies will be necessary to determine the clinical efficacy and toxicity in men with BPH.

Thermal model for the local microwave hyperthermia treatment of benign prostatic hyperplasia.

A system for the noninvasive localized, hyperthermia treatment of benign prostatic hyperplasia was investigated. The system uses a microwave transrectal antenna with a water cooled jacket to achieve localized hyperthermia. The purpose of this study is to model the temperature rise in the prostate and in the surrounding tissue during treatment. The SAR distribution for the transrectal probe is measured in a muscle tissue equivalent phantom. The SAR information is used with a finite element solution of the bioheat transfer equation to give the temperature rise during the treatment. Also the finite element solution is further used to determine the effect of the microwave power, the cooling fluid temperature and the blood perfusion on the tissue temperature rise. The results of the solution are compared to temperature measurements in a canine protocol. It was found that the maximum temperature rise in the tissue during treatment is 44 degrees C at a depth of 2 cm from the rectal mucosa.

Local microwave hyperthermia as a treatment alternative for benign prostatic hyperplasia.

It appears that the technology for local microwave application of heat to the prostate for the management of benign prostatic hyperplasia has arrived. There are a number of issues to be resolved in the coming years that will determine the role this modality will play in the overall management of men with benign prostatic hyperplasia. These issues include: transurethral versus transrectal route, hyperthermia (42 degrees C to 44 degrees C) versus thermotherapy (greater than 45 degrees C), and a proper assessment as to whether the technique is really efficacious, given the known placebo response in all studies currently available. The results with the transrectal route appear to improve patients' symptoms objectively and subjectively, without causing irreversible tissue effects. Thus, its action has been likened to alpha blockade. But, it appears that the transrectal approach is relatively inefficient because of a significant loss in microwave power with rectal cooling. A probe placed transurethrally can accurately and easily deliver the intended power to the center of the prostate, where theoretically it has its greatest effect on both the dynamic and static components of outlet obstruction. Currently, the transurethral devices described by Sapozink and Devonec will produce histologic necrosis. The theoretical value of combining urethral heating with cooling is that it will allow treatments of greater power deeper in the prostate adenoma, but the greatest advantage over transurethral heating without cooling may be in the ability to effect a response in a single session. Finally, the placebo response is a well known phenomenon seen in all drug trials conducted for the management of benign prostatic hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Rehabilitation and biomechanics

In the area of rehabilitation and biomechanics, several articles divided into five categories, including therapeutic heat, foot and ankle orthotics, exercise in elderly arthritis patients, muscle strengthening in rheumatoid arthritis, and arthroplasty and immobilization are reviewed. Superficial heat was demonstrated to increase intra-articular temperature, and therefore, may be detrimental. On the other hand, local deep microwave hyperthermia appears to have potential therapeutic benefits. The role and effectiveness of foot orthotic devices are reviewed. The problem and treatment of forefoot varus is emphasized. A new technique of measuring subpedal pressure in the shoe is presented, demonstrating reduced foot pressures by certain types of footwear. Rheumatoid arthritis and osteoarthritis wee present in 23% of a nursing home population, but were a substantial factor for placement in only 15%. However, this group had higher pain scores, depended more on wheelchair use, and was more likely to have significant functional limitations. Exciting new data on strengthening the quadriceps in the frail elderly, whose mean age was 90.2 years, are reviewed. The relationship of quadriceps muscle strength and maximum voluntary strength as a function of age and gender and the effects of an endurance training program in 15 physically compromised nursing home residents is discussed. A static and a dynamic training program for rheumatoid arthritis patients were compared. The dynamic group significantly increased muscle strength, endurance, and aerobic capacity as compared to the static group, without any increase in disease activity. The results further showed that a home program was beneficial. Interesting data presented show that using a Cybex isokinetic dynamometer (Lumex, Bayshore, NY) test was reliable for normal control and for rheumatoid arthritis patients who were stronger.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Abacterial Prostatitis and Hyperthermia A Possible New Treatment?

A group of 45 patients with chronic abacterial prostatitis or prostatodynia underwent 6 weekly, 1-hour sessions of local deep microwave hyperthermia (42.5 +/- 0.5 degrees C) to the prostate. All patients had a long history of symptoms typical of the condition. They all failed to respond to a variety of conventional treatments administered over several years by various specialists. Each patient served as his own control before and after the hyperthermic treatment. The results of this study are encouraging: 25% showed a sustained and complete loss of symptoms and 50% had a partial response; the remaining 25% reported no improvement. These results open up new possibilities in the treatment of this condition, which has so far responded poorly to conventional therapy.

Local-Regional Recurrences of Breast Cancer

From October 1981 through September 1988, 31 local-regional recurrences of breast cancer in 26 patients were treated at the Oncology Center in Trento, Italy, with a combination of external radiation therapy (XRT) and superficial local microwave hyperthermia (Ht). The mean total XRT dose was 37.40 Gy, ranging from 19.80 to 60.00 Gy, depending on the extent of previous irradiation. Ht was delivered using the same superficial mw applicator, operating at frequencies between 280 and 480 MHz. The goal was to obtain a minimum intra- and peritumoral temperature of 42.5 degrees C for 30 min. Ht was applied immediately after XRT, 2 or 3 times per week for a total of 1-9 sessions (median 2). Thirty lesions (97%) could be evaluated for response 3 months after the end of the combined treatment. Twenty (66.6%) complete responses, seven (23.3%) partial responses, and three (10%) with no change were observed. No significant acute local side effects were noted, with the exception of two thermal burns and one ulceration. Patients achieving complete response show actuarial long-term local control of 87.8% at 3 years. In our experience, Ht combined with a low/moderate XRT dose may be particularly valuable in the palliation of recurrences in previously irradiated regions. Excellent response rates can be obtained when Ht is combined with a radical dose of irradiation.

Histological effects of local microwave hyperthermia in prostatic cancer

Recent investigations have shown that hyperthermia can reduce the volume of the prostate and improve local symptoms in patients with carcinoma of the prostate. Histological examinations of the effect of hyperthermia on prostatic cancer tissue, however, have not been performed systematically until now. Thus, we initiated a study to investigate the effects of heat on prostatic cancer as a prerequisite for further clinical trials on hyperthermia as treatment for prostatic cancer. Twenty patients with untreated prostatic cancer underwent local hyperthermia (915 MHz), each receiving four sessions of 60 min each. The intraprostatic temperature was 42-43 degrees C. Histological specimens of the prostate were taken before the treatment and 1-2 weeks after the last hyperthermia session. Hyperthermia produced hyperaemic alterations of the prostatic stroma and a diffuse oedema with interstitial lymphoplasmacellular infiltration. Definite signs of tumour cell necrosis, however, could not be seen in any of the patients. Hence the shrinkage of prostatic tumours described earlier cannot be explained by histologically proven tumour cell destruction. Thus hyperthermia is not adequate as a single treatment for prostatic cancer. Hyperthermia may, however, be useful as part of integrated therapy regimens together with cytostatic or hormonal agents and radiotherapy because of hyperaemic, chemo- and radiosensitizing effects.

The Effect of Local Deep Microwave Hyperthermia on Experimental Zymosan-induced Arthritis in Rabbits

The effect of local deep microwave hyperthermia (LDMWH) on normal and Zymosan-induced arthritis has been evaluated in 12 rabbits (24 joints). LDMWH, four treatments to each joint (twice weekly for a period of 2 wk), was generated by an antenna operating at 915 MHz for 60 min, reaching an intraarticular temperature of 42.5 +/- 0.5 degrees C. A surface cooling system was used with the microwave apparatus. Two weeks after the last treatment, all animals were sacrificed. The application of LDMWH on normal joints induced a limited proliferation of the synovial lining cells with a minimal perivascular infiltration of mononuclear and neutrophil cells. However, no histologic damage to the skin, muscles, bone, cartilage or bone marrow adjacent to the heated joints could be noted. Induction of Zymosan arthritis (2 wk before LDMWH) was characterized by pannus formation and granulomatous reaction accompanied by fibrinoid deposits and disseminated necrotic foci in the synovial intima. The LDMWH treatment on the examined arthritic joints brought about a reduction in the degree of granulomatous reaction concomitant with the appearance of some fibrocytes and fine collagen fibrils. These findings suggest that LDMWH can be safely applied, even repeatedly, without morphologic evidence of damage to any normal mesenchymal tissue. Moreover, it reduces the inflammatory process in experimentally induced synovitis.

Local Microwave Hyperthermia of Benign Prostatic Hyperplasia

Recently, hyperthermia has been used for treatment of benign prostatic hyperplasia. The preliminary results reported were promising. However, apart from patients with total urinary retention, objective voiding parameters have not been reported in detail for patients with prostatism. In a phase II study we treated 30 patients with benign prostatic hyperplasia by local microwave hyperthermia (915MHz.). The prostate was heated transrectally to 42 to 43C, with the treatment consisting of 8 sessions of 60 minutes each given twice a week. To assess the results of treatment several parameters were determined before and 4 weeks after hyperthermia therapy, including transrectal ultrasound of the prostate with volumetry, urinary flow rate and residual volume. Of the patients 28 could be evaluated and only 2 showed a relevant improvement. Neither the voiding parameters nor the size of the prostate could be changed significantly by hyperthermia. The success rate of 7.1% is even lower than the spontaneous temporary regression rate of benign prostatic hyperplasia. Thus, we believe that hyperthermia cannot be regarded as an effective treatment for benign prostatic hyperplasia comparable to transurethral resection. (J. Urol., 144: 913–917, 1990)

Local Microwave Hyperthermia in the Treatment of Benign Prostatic Hypertrophy

Local deep microwave hyperthermia has been introduced recently for the treatment of benign prostatic hypertrophy (BPH). We report the results of treatment in 114 patients divided into 2 groups. The first group included 83 patients with severe obstructive symptoms. Although some improvement was found in the scoring of both subjective and objective parameters, the number of patients benefiting was small, with only 28% showing improvement in both parameters. Approximately 50% reported subjective improvement but in only 25% was this significant. In 42% there was objective evidence of improvement. Prostatic volumes did not change as a result of treatment. The second group comprised 31 patients with indwelling catheters because of acute urinary retention. After treatment, 19 patients (61%) were able to dispense with the catheter. The difficulties of interpreting an open trial of treatment for BPH and assessing its impact on objective parameters and symptomatology are discussed. Our results should be regarded cautiously in view of these reservations.

Local hyperthermia to canine prostateA pilot study

Repeated treatments of localized deep microwave hyperthermia were given to a series of dogs by means of a 915 MHz, water-cooled skirt-type applicator. The applicator was inserted into the rectum and directed toward the prostate in order to heat it by means of the absorbed microwaves while keeping the rectal wall at a lower temperature by surface cooling of the aplicator itself. Sessions were given for different lengths of time ranging between ninety minutes and five hours, during which the prostate temperature was kept at 42.5°C (± 0.5°C) or 44.5°C (± 0.°C). Three-dimensional temperature distributions in the prostate were measured accurately and verified by a Luxtron Fluoroptic Unit. Temperatures were constantly monitored in the rectal wall and in the prostatic urethra. Thorough and systemic follow-up was done before, during, and after each treatment, and the observations are reported. Two interesting preliminary observations were made: (1) differential blood counts showed significant monocytosis following the treatments and lasted for at least one week, and (2) values of creatinine phosphokinase (CPK) and serum glutamic oxaloacetic transaminase (SGO T) were found to rise irreversibly in those animals which were later found to have definite histopathologic evidence of localized necrotic damage.

Measurement of tumor ph during microwave induced experimental and clinical hyperthermia with a fiber optic pH measurement system

The influence of hyperthermia on tissue pH was investigated using a modified version of the fiber optic monitoring system. This newly developed system was tested for use in tissues and found to be suitable for pH measurement during microwave induced hyperthermia. The fiber optic pH probe (0.7 mm diameter) could be easily used in the electromagnetic fields produced by the microwave applicators, whereas only the display unit required some shielding. Tissue pH of experimental and clinical tumors was measured concurrently with local microwave hyperthermia treatment. The mean initial intratumor pH of a rat rhabdomyosarcoma was 7.03 (SD 0.13, n = 19) and the pH of human subcutis was 7.45 (SD 0.02, n = 8). In rat tumor a primary pH decrease was observed during heating which was fully reversed during cooling. The coefficient of temperature dependence was -0.016 pH unit/°C (SD 0.004, n = 12). After approximately 1 hr of heating at 43°C a further pH decrease of 0.1–0.3 unit occurred which was not reversed directly after treatment. Measurements during clinical local microwave hyperthermia treatments after radiotherapy revealed similar changes in pH values, primary as well as secondary. The estimated coefficient of temperature dependence for the reversible pH change, which occurred in subcutis as well as in tumor tissue, was −0.016 pH unit/°C (SD 0.004, n = 12). The fiber optic pH measurement system is expected to be a valuable tool in the thorough investigation of temperature and time related pH changes in tumor during experimental as well as clinical hyperthermia treatment.

Treatment of articular effusions with local deep microwave hyperthermia.

Local deep microwave hyperthermia (LDMWH) may be considered as a therapeutic tool for joint diseases because it has the advantage of heating the target organ e.g. synovium, while sparing the adjacent tissues, as demonstrated in animals. The effect of this new microwave device has been evaluated on seven rheumatoid arthritis patients with knee effusion. The hyperthermia apparatus consists of a 915 MHz power source with a cooling system to the skin. LDMWH was operated for one hour, twice a week for two weeks. Intra-articular knee temperature reached the level of 40.6 +/- 1.1 degrees C within 15 minutes, raised to 41.2 +/- 0.7 degrees C after 30 minutes and to 41.3 +/- 0.9 degrees C at one hour. The skin temperature over the heated knee joints remained at 24.3 +/- 1.1 degrees C during treatment. All patients noted a sensation of warmth in the treated knee. Aspiration of synovial fluid was performed before and immediately after each treatment. Walking time was improved (p = 0.04) and significant decrease in pain (p = 0.01) was noted following treatment. Synovial fluid leukocyte count and prostaglandin E2 level, knee circumference and range of motion did not change. Severity of pain, walking time, knee circumference and range of motion remained stable in the six weeks following the last hyperthermia application. No adverse reaction could be observed. These results suggest LDMWH to be safe and successful as an adjuvant treatment of chronic inflammatory joint effusions.