Single application of high-intensity focused ultrasound as primary therapy of localized prostate cancer: Treatment-related predictors of biochemical outcomes.

OBJECTIVE: Recent reports on high-intensity focused ultrasound (HIFU) treatment of localized prostate cancer suggest that preoperative risk groups of tumor recurrence are strong predictors of oncological outcomes. The purpose of this study is to determine the prognostic significance of treatment-related factors in relation to patient characteristics for biochemical outcomes after HIFU. METHODS: This retrospective single-center study included patients treated from December 2002 to December 2010 for localized prostate cancer with two generations of Ablatherm® HIFU devices (A1 and A2). All the patients underwent single HIFU treatment session under the concept of whole-gland therapy. Prostate surgery was performed before HIFU to downsize enlarged glands. Androgen deprivation therapy (ADT) was discontinued before HIFU. Biochemical failure (BCF) was defined as prostate specific antigen (PSA) nadir + 1.2 ng/mL (Stuttgart definition). Predictors of BCF were determined using Cox regression models. As covariates, patient-related factors (age, tumor characteristics, ADT) were compared with treatment-related factors (prostate volume, HIFU device generation, conduct of therapy, prostate edema, patient movement, anesthetic modalities). RESULTS: Three hundred and twenty-three (98.8%) out of 327 consecutive patients were evaluable for BCF. Median (interquartile range) follow-up was 51.2 (36.6-80.4) months. The overall BCF-rate was 23.8%. In multivariate analyses, higher initial PSA-values (Hazard ratio [HR]: 1.03; p < 0.001) and higher D'Amico risk stages (HR: 3.45; p < 0.001) were patient-related predictors of BCF. Regarding treatment-related factors, the A2 HIFU device was associated with a decreased risk of BCF (HR: 0.51; p = 0.007), while prostate edema had an adverse effect (HR: 1.8; p = 0.027). Short follow-up and retrospective study design are the primary limitations. CONCLUSION: Success in a single HIFU session depends not merely on tumor characteristics, but also on treatment-related factors. Ablation is more efficacious with the technically advanced A2 HIFU device. Heat-induced prostate edema might adversely affect the outcome.

Interleukin-3 is elevated in patients with coronary artery disease and predicts restenosis after percutaneous coronary intervention.

BACKGROUND: Interleukin-3 (IL-3) synthesized by activated T-lymphocytes is a mediator in chronic inflammation and is suspected to promote atherosclerosis. Since there is no data on IL-3 in patients with coronary artery disease (CAD) available, we compared IL-3 concentrations in different subsets of patients with CAD to healthy control patients. METHODS: 205 consecutive patients with CAD, 136 with stable angina and 69 with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention, 61 patients with asymptomatic CAD and 41 patients with normal coronary arteries were investigated. Serum concentrations of IL-3 and hs-CRP were assessed at baseline and after 6 weeks, 6, and 12 months. RESULTS: In patients undergoing coronary angioplasty, IL-3 was detectable more frequently than in those with asymptomatic CAD or without CAD, 21 vs. 8%, p=0.02, and 21 vs. 1%, p<0.001, respectively. Patients undergoing coronary angioplasty who developed symptomatic restenosis more frequently had detectable IL-3 levels than patients without restenosis, 45 vs. 17%, p=0.02. IL-3 was the only independent predictor for restenosis in a multivariate analysis. Hs-CRP was significantly elevated in patients with ACS, 230+/-170 mg/l vs. 100+/-140 mg/l, p=0.02, but did not correlate with IL-3 concentrations at any time. CONCLUSION: IL-3, an important regulator of chronic inflammation, is elevated in patients with CAD, particularly in symptomatic patients undergoing percutaneous coronary intervention. Furthermore, high IL-3 concentrations were found to be predictive of symptomatic restenosis.

Heroin-assisted treatment for opioid dependence: randomised controlled trial.

BACKGROUND: Heroin-assisted treatment has been found to be effective for people with severe opioid dependence who are not interested in or do poorly on methadone maintenance. AIMS: To study heroin-assisted treatment in people on methadone who continue intravenous heroin and in those who are heroin dependent but currently not in treatment. METHOD: In an open-label multicentre randomised controlled trial, 1015 people with heroin dependence received a variable dose of injectable heroin (n=515) or oral methadone (n=500) for 12 months. Two response criteria, improvement of physical and/or mental health and decrease in illicit drug use, were evaluated in an intent-to-treat analysis. RESULTS: Retention was higher in the heroin (67.2%) than in the methadone group (40.0%) and the heroin group showed a significantly greater response on both primary outcome measures. More serious adverse events were found in the heroin group, and were mainly associated with intravenous use. CONCLUSIONS: Heroin-assisted treatment is more effective for people with opioid dependence who continue intravenous heroin while on methadone maintenance or who are not enrolled in treatment. Despite a higher risk, it should be considered for treatment resistance under medical supervision.

A patient questionnaire for radiation-induced brachial plexopathy.

We analyzed the usefulness of a symptom questionnaire to screen for radiation-induced brachial plexopathy (RIBP) after breast cancer treatment. Four questions addressed distal and proximal paresis: impaired hand functions, problems raising the arm, carrying weights, and lifting objects from a high shelf. Eighty-one relapse-free patients were neurologically examined. Treatment was mastectomy (51%) or breast-conserving surgery (49%), radiotherapy to the supraclavicular +/- axilla with median 60 Gy maximum dose. Sixty-five subsequent control patients had breast-conserving surgery and radiotherapy to the breast only with 55 Gy median dose. Median follow up was 10 and 7.4 years, respectively. Sixteen patients had RIBP, 7 had Radiation Therapy Oncology Group (RTOG) grade 1, 4 grade 2, 3 grade 3, and 2 grade 4 RIBP. Thirty-seven patients had fibrosis and 32 had arm edema. Four patients with RIBP had no fibrosis (n = 2) or fibrosis of the axilla only (n = 2). Specificity of the question "impaired hand functions" for RIBP was 0.66 (95% confidence interval [CI], 0.51-0.78); sensitivity was 0.80 (95% CI, 0.52-0.96). Specificity of the question "raising the arm" was 0.98 (95% CI, 0.9-0.99) and sensitivity was 0.18 (95% CI, 0.04-0.45); the rate of false-positive control patients was 3%. In multivariate analysis, "impaired hand functions" and fibrosis were independent indicators of RIBP (P <0.005). Patients with breast irradiation only stated moderate/pronounced impaired hand functions; and problems carrying weights and lifting objects from a high shelf in 38%, 58%, and 77%, not significantly different from patients with RIBP or the patients with supraclavicular radiation. RIBP is not necessarily associated with fibrosis. The aim of the questionnaire was screening of a population at risk for RIBP. In this group, the question "problems raising the arm" detected severe RIBP with high specificity. Negation of "impaired hand functions" excludes RIBP. Both questions should be included in follow-up questionnaires.

Prognostic value of placental growth factor in patients with acute chest pain.

CONTEXT: Experimental data suggest that placental growth factor (PlGF), a member of the vascular endothelial growth factor family, acts as a primary inflammatory instigator of atherosclerotic plaque instability and thus may be useful as a risk-predicting biomarker in patients with acute coronary syndromes (ACS). OBJECTIVE: To determine whether blood levels of PlGF predict risk for death or nonfatal myocardial infarction in patients with acute chest pain. DESIGN, SETTING, AND PATIENTS: Measurement of PlGF levels as well as levels of markers of myocardial necrosis (troponin T [TnT]), platelet activation (soluble CD40 ligand [sCD40L]), and inflammation (high-sensitivity C-reactive protein [hsCRP]) in an inception cohort of 547 patients with angiographically validated ACS participating in the CAPTURE (c7E3 Fab Anti-Platelet Therapy in Unstable Refractory Angina) trial and in a heterogeneous cohort of 626 patients presenting with acute chest pain to an emergency department in Germany between December 1996 and March 1999. MAIN OUTCOME MEASURE: Risk for death or nonfatal myocardial infarction after 30 days. RESULTS: In patients with ACS, elevated PlGF levels (>27.0 ng/L; 40.8% of patients) indicated a markedly increased risk of events at 30 days (14.8% vs 4.9%; unadjusted hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.79-6.24; P<.001). In a multivariable model, elevated levels of TnT (HR, 1.83; 95% CI, 1.05-3.86; P =.03), sCD40L (HR, 2.65; 95% CI, 1.41-4.99; P =.002), and PlGF (HR, 3.03; 95% CI, 1.54-5.95; P<.001) were independent predictors, while elevated hsCRP level was not (HR, 0.98; 95% CI, 0.53-1.98; P =.94). In patients with acute chest pain, elevated levels of PlGF predicted risk (21.2% vs 5.3%) (unadjusted: HR, 4.80; 95% CI, 2.81-8.21; P<.001; adjusted: HR, 3.00; 95% CI, 1.68-5.38; P<.001). Patients negative for all 3 markers (TnT, sCD40L, and PlGF) were at very low cardiac risk (7 days: no event; 30 days: 2.1% event rate). CONCLUSIONS: Plasma PlGF levels may be an independent biomarker of adverse outcome in patients with suspected ACS. A single initial measurement of plasma PlGF appears to extend the predictive and prognostic information gained from traditional inflammatory markers.

Cosmesis from the patient's and the doctor's view.

PURPOSE: Long-term cosmesis from the patient's perspective is compared to the doctor's appraisal. Factors that determine judgment of cosmesis are analyzed. Also, a patient questionnaire was designed to screen for normal tissue reactions and is evaluated. METHODS AND PATIENTS: With structured questions, patients rated their satisfaction considering cosmesis, the difference in overall appearance, and specific changes of the breast. Two doctors rated cosmesis and radiation late effects (LENT/SOMA). Ratings were compared, and the relative impact of single items was studied. Two hundred eighty-seven patients with unilateral breast carcinoma were examined after a median follow-up of 8 years. They were treated between 1981 and 1995 with lumpectomy and radiotherapy of the breast with 1.8-2.5 Gy fractions with a median total dose of 55 Gy (range: 50-65 Gy). RESULTS: One hundred sixty-one patients rated cosmesis as satisfying, 73 patients rated it as acceptable, and 25 patients as poor. Eighty-nine patients noted severe changes of appearance. Severe firmness and extensive scars were the most frequent complaint; the most important single item for judging cosmesis as poor was highly visible scars. Generally, doctors rated cosmesis less favorably (satisfactory, 150 patients; poor, 43 patients). Severe fibrosis was more important than discoloration of the breast or scars. Correlation between patients' and doctors' rating of cosmesis was modest (Cohen's weighted kappa 0.29), whereas the doctor's rating correlated well (0.55). Specificity and sensitivity of the questionnaire item for severe fibrosis (using doctors' judgments as gold standard) was 0.8; Cohen's weighted kappa was 0.34 (95% confidence interval: 0.21-0.48). CONCLUSION: Rating of cosmesis is subjective. Patients' satisfaction with cosmesis is greater than the doctors' and is determined not only by radiation late effects, but also by factors unrelated to the appearance of the breast. Severe fibrosis may be detected by a patient questionnaire.