Interstitial microwave thermal therapy for prostate cancer: method of treatment and results of a phase I/II trial

PURPOSE: Interstitial microwave thermal therapy is experimental treatment for prostate cancer with the goal of curing disease, while causing fewer complications than standard treatment options. We present a method for delivering interstitial microwave thermal therapy using microwave radiating helical antennae inserted percutaneously under transrectal ultrasound guidance. We report the results of a trial of this method in 25 patients in whom primary external beam radiation therapy had previously failed. This patient group currently has limited curative options that are associated with a high complication rate. However, these recurrent tumors often remain localized to the prostate, and so they may be amenable to localized therapy. MATERIALS AND METHODS: Patients with proved prostatic adenocarcinoma were candidates for treatment when prostate specific antigen (PSA) was 15 ng./ml. or less and prostate volume was 50 cc. or less. Followup included PSA measurement, digital rectal examination, urinalysis, and documentation of adverse events at 4, 8, 12 and 24 weeks. Sextant biopsy was performed at week 24. The procedure involved the insertion of 5 antennae percutaneously through a modified brachytherapy template. The antenna arrangement was determined based on computer simulated predictions of temperature throughout the prostate. The prostate was dissected away from the rectum by an injection of sterile saline to provide a thermal barrier that protected the rectum from thermal damage. Temperatures were monitored using interstitial mapping thermistor probes that were also inserted through the template. A minimum peripheral target temperature of 55C but less than 70C was maintained for 15 to 20 minutes, while the urethra, rectum and hydrodissection space remained below 42C. The urethra and rectum were actively cooled in addition to hydrodissection. RESULTS: Peripheral target temperatures of 55C were achieved. The urethra and rectum remained at a safe temperature. The procedure, including setup and treatment, required approximately 2.5 hours of operating room time. At 24 weeks the PSA nadir was 0.5 ng./ml. or less in 52% of patients and 0.51 to 4 ng./ml. was achieved in an additional 40%. The negative biopsy rate at 24 weeks was 64%, assuming that 3 patients lost to followup would have had positive results. No major complications were observed and in most cases minor complications resolved within 3 months. CONCLUSIONS: Interstitial microwave thermal therapy for prostate cancer was developed to heat the prostate safely to a cytotoxic temperature. Experience with 25 patients in whom external beam radiation therapy for prostate cancer had failed indicates that the treatment is safe. Although our series indicates that this therapy may be effective, further studies and longer followup are required in larger patient groups to confirm the potential role of this therapy as an option for recurrent and primary prostate cancer.     

Premature atherosclerosis in systemic lupus erythematosus

Significant advances have been made in defining the spectrum of clinical manifestations and the prognosis of systemic lupus erythematosus (SLE). With the use of corticosteroids and other immunosuppressive agents as well as better management of complications such as infection, there has been a dramatic improvement in the short-term prognosis of patients who have SLE from less than 50% survival at 5 years to 93% at 5 years and 85% and 10 years. However, many patients who survive early complications of organ failure and sepsis later develop premature coronary artery disease (CAD). In this evidence-based review, the magnitude of the problem of premature atherosclerosis in SLE is defined and evaluation of the strength of association of risk factors determined to date. The authors focus on the emerging role of new modalities for noninvasive assessment of vascular health in patients who have SLE and offer a strategy for screening and management of those at risk of CAD. The article concludes with a discussion on the important questions that remain to be answered and future directions for research.     

Psoriatic arthritis

Although there is still some controversy about the existence of psoriatic arthritis as a specific form of inflammatory arthritis associated with psoriasis, epidemiological, and clinical studies support the unique features of psoriatic arthritis. Because of lack of diagnostic or classification criteria, the disease has been thought of as uncommon. Over the past several decades, it has become clear that the disease leads to serious disability and even increased mortality. Traditional medications have not been effective in preventing the progression of joint damage. New medications, including biologics, have emerged with the potential to control the inflammation and arrest the progression of joint damage.     

The SLICC/ACR damage index: progress report and experience in the field

The SLICC/ACR damage index for SLE was developed to assess accumulated damage since the onset of the disease. The damage includes non-reversible changes in organs and systems affected by the disease process itself, its therapy, or inter-current illness. This paper describes the development of the damage index, its validation and its use. It is recommended as an outcome measure for longitudinal studies of prognosis and response to new therapies, and as a stratification measure for clinical trials.     

Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus.

OBJECTIVE: To describe the frequency and type of symptomatic osteonecrosis (ON) in a large cohort of patients with systemic lupus erythematosus (SLE) followed in a single center and to describe the outcome in terms of mortality and disability compared to SLE patients without ON. METHODS: Patients with ON were identified from the University of Toronto Lupus Clinic Database. The diagnosis of ON was confirmed by radiographs, bone scans, tomograms, or magnetic resonance images. A comparison group of patients with SLE without ON was selected from the same database, matched by year of birth, sex, and year of entry to the clinic. Mortality, disability, and health related quality of life were compared between patients with and without ON. RESULTS: Ninety-nine patients with ON were identified with 217 affected joints, the majority hips and knees, often in a bilateral distribution. There was no increase in mortality. Patients with ON had higher Health Assessment Questionnaire scores and lower SF-20 scores of physical functioning, suggesting increased disability. Hip joints that underwent surgery were more likely to have higher grades of ON at diagnosis. CONCLUSION: Symptomatic ON occurred in 12.8% of 744 patients with SLE and often involved multiple joints. ON was not associated with increased mortality but was associated with physical disability. Radiological class of the hip jointsat diagnosis of ON was predictive of subsequent surgery.     

Extrarenal disease activity in systemic lupus erythematosus is not suppressed by chronic renal insufficiency or renal replacement therapy.

OBJECTIVE: To assess whether chronic renal impairment (CRI) and/or renal replacement therapy (RRT) in systemic lupus erythematosus (SLE) are associated with reduced extrarenal SLE activity. METHODS: This was a retrospective cohort analysis of patients with SLE who are followed at the University of Toronto Lupus Clinic. Patients with SLE were studied in 2 stages; chronic renal insufficiency (defined as a serum creatinine > 200 mumol/1 for > 6 months) and following the institution of dialysis therapy. Controls consisted of the next 2 age and sex matched patients in the clinic with a history of lupus nephritis who had not developed renal insufficiency. We assessed the flare rate (an increase in nonrenal SLEDAI > or = 1.0) for patients and controls in the first 12 months of followup at the clinic in each stage. RESULTS: Twenty-one patients, 17 female and 4 male, were followed through 25 episodes of CRI or RRT as were 50 controls. In the CRI stage (n = 12), flares occurred in 8 (67%) within one year compared to 14 (58%) of 24 controls (p = NS). In the RRT stage (n = 13), flares occurred in 7 (54%) compared to 16 (62%) of 26 controls (p = NS). The magnitude as well as the characteristics of the flares did not differ between patients and controls in either stage. CONCLUSION: Patients with SLE who develop CRI, or who receive RRT, continue to display evidence of ongoing extrarenal disease activity. Such patients require careful longterm followup for management of their extrarenal disease.     

Psoriatic spondyloarthropathy in men and women: a clinical, radiographic, and HLA study.

Psoriatic spondyloarthropathy as defined by the presence of inflammatory back pain and stiffness, sacroiliitis on physical examination, radiographic evidence of grade greater than or equal to 2 sacroiliitis, and classical or paramarginal syndesmophytes on spinal radiographs was identified in 82 women and 112 men followed at the Psoriatic Arthritis Clinic according to a standard protocol. A logistic regression analysis was performed to look for variables which discriminate between men and women with this condition. No differences in type of peripheral arthritis, degree of damage, or medication were noted between the two groups. However, there was some evidence for more advanced spondyloarthropathy in men. There were no differences in the frequency of HLA B27 or any of the psoriatic arthritis-related HLA antigens. Thus, there may be gender-related differences in the expression of psoriatic spondyloarthropathy, which are unrelated to HLA antigens.