Christian Kratzik

PSA, PSA DENSITY, PSA DENSITY OF TRANSITION ZONE, FREE/TOTAL PSA RATIO, AND PSA VELOCITY FOR EARLY DETECTION OF PROSTATE CANCER IN MEN WITH SERUM PSA 2.5 TO 4.0 ng/mL

OBJECTIVES To enhance the specificity of prostate cancer (PCa) detection and reduce unnecessary biopsies in men with prostate-specific antigen (PSA) levels of 2.5 to 4.0 ng/mL, we prospectively evaluated various PSA-based diagnostic parameters. METHODS This study included 273 consecutive men with serum PSA of 2.5 to 4.0 ng/mL referred for early PCa detection or lower urinary tract symptoms. All men underwent prostate ultrasound and sextant biopsy with two additional transition zone (TZ) biopsies. If the first biopsies were negative, repeated biopsies were performed at 6 weeks. Total PSA, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), free/total PSA ratio (f/t PSA), and PSA velocity (PSAV) were determined, and the sensitivity, specificity, and predictive values of these various parameters were calculated. RESULTS Of 273 patients, 207 had histologically confirmed benign prostatic hyperplasia (BPH) and 66 had PCa. f/t PSA and PSA-TZ were the most powerful predictors of PCa, followed by PSA, PSAD, and PSAV. Areas under the receiver operating characteristic curves for f/t PSA and PSA-TZ were 74.9% and 70.1%, respectively. With a 95% sensitivity for PCa detection, an f/t PSA cutoff of 41% and a PSA-TZ cutoff of 0.095 would result in the lowest number of unnecessary biopsies (29.3% and 17.2% specificity for f/t PSA and PSA-TZ, respectively) compared with all other PSA-related parameters evaluated. CONCLUSIONS Compared with standard total PSA assays, f/t PSA and PSA-TZ significantly enhance the sensitivity and specificity of PCa detection in a referral patient population with a total PSA of 2.5 to 4.0 ng/mL.

Morphology of tissue destruction induced by focused ultrasound.

The effect of high-intensity focused ultrasound (HIFU) ablation on the morphology of prostatic, renal and testicular tissue was studied by light and electron microscopy. Specimens were obtained in 21 patients 1 h to 10 weeks after lesioning. Histological findings showed consistent coagulative necrosis with precisely defined, sharp margins to normal tissue. Lesion size and position correlated well with the assumed target zones, suggesting that HIFU permits therapeutic tissue ablation.

Tissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound.

In a phase I clinical trial the morphological impact and safety of high intensity focused ultrasound administered transrectally for tissue ablation in prostates from 22 patients undergoing subsequent prostatectomy were evaluated. Location and size of the tissue lesions correlated well with the predefined target area and revealed sharply delineated coagulative necrosis in all cases. Intervening tissues, such as the rectal wall and posterior prostate capsule, were invariably intact. In a subsequent phase II clinical trial the effectiveness of transrectal high intensity focused ultrasound as a novel minimally invasive treatment modality for 50 patients with symptomatic benign prostatic hyperplasia was determined. The maximum urinary flow rate (ml. per second) increased from 8.9 +/- 4.1 to 12.7 +/- 6.4 at 3 months in 44 patients, 12.4 +/- 5.6 at 6 months in 33 and 13.1 +/- 6.5 at 12 months in 20. During the same period the post-void residual volume (ml) decreased from 131 +/- 120 to 48 +/- 41, 59 +/- 42 and 35 +/- 30, respectively, and the American Urological Association symptom score (points) decreased from 24.5 +/- 4.7 to 13.3 +/- 4.4, 13.4 +/- 4.7 and 10.8 +/- 2.5, respectively. These data demonstrate that transrectal high intensity focused ultrasound is capable of inducing coagulative necrosis in the human prostate via a transrectal approach while preserving intervening and adjacent tissue. A 47% (+4.2 ml. per second) improvement in uroflowmetry and a 53% (-13.7 points) decrease in the American Urological Association symptom score 1 year after treatment clearly prove that transrectal high intensity focused ultrasound is a novel and safe minimally invasive treatment option for benign prostatic hyperplasia.

Twelve-Year Experience With Two Courses of Adjuvant Single-Agent Carboplatin Therapy for Clinical Stage I Seminoma

PURPOSE During the past 30 years, radiation therapy with 28 to 30 Gy for para-aortic and ipsilateral iliac node areas was the standard adjuvant treatment for clinical stage I seminoma after orchiectomy. However, late effects of radiotherapy prompted a search for alternative adjuvant treatment approaches, including surveillance and application of carboplatin. In this retrospective analysis, we evaluated the efficacy and toxicity of two adjuvant single-agent carboplatin courses in 107 patients who were diagnosed with clinical stage I seminoma at our study centers between 1988 and 1999. PATIENTS AND METHODS All 107 patients (median age, 39 years; range, 24 to 63 years) received two postoperative adjuvant cycles of carboplatin (400 mg/m(2)). The pathologic tumor stage was pT1 in 84 patients, pT2 in 18 patients, and pT3 in five patients. Whole blood count and serum chemistry were evaluated weekly during treatment to assess hematologic and nonhematologic toxicity. RESULTS Six patients died from tumor-unrelated causes. The remaining 101 patients are currently alive and free of disease after a median follow-up of 74 months (range, 5 to 145 months). A detailed analysis of hematologic toxicity showed only World Health Organization (WHO) grade 1 leukocytopenia in 10.7% of all cycles and WHO grade 2 leukocytopenia in 2.1% of all cycles. CONCLUSION Regarding the absence of tumor recurrences in our retrospective analysis and the favorable toxicity profile with no episodes of long-term toxicity, we suggest that two adjuvant courses of single-agent carboplatin for clinical stage I seminoma patients might be equivalent to radiotherapy.

How Much Physical Activity Is Needed To Maintain Erectile Function? Results of the Androx Vienna Municipality Study

OBJECTIVE To assess the correlation of erectile function (EF) and physical activity (PhA) by using standardized, validated instruments in healthy men. METHODS A urologist examined 674 men aged 45-60 yr at their place of work. That included a urological physical examination, medical history, and assessment of testosterone (T) and sex hormone-binding globulin; all men completed the 5-item International Index of Erectile Function (IIEF-5) as well as the Paffenbarger score. PhA was assessed in kilojoules per week (4.2 kJ=1 kcal). RESULTS A positive correlation between the IIEF-5 and the Paffenbarger score (r=0.164, p<0.001) was found. The IIEF-5 score increased with an increasing Paffenbarger score up to a level of 4000 kcal/wk. T revealed a trend to a significant impact on the IIEF-5 score, but showed no association with the Paffenbarger score. The risk of severe erectile dysfunction (ED) was decreased by 82.9% for males with PhA of at least 3000 kcal/wk compared with males with PhA under 3000 kcal/wk (OR=0.171, p=0.018). CONCLUSION Increasing PhA from 1000 to 4000 kcal/wk may reduce the risk of ED.

Transcutaneous High-Intensity Focused Ultrasound and Irradiation: An Organ-Preserving Treatment of Cancer in a Solitary Testis

Objectives: The aim of this study was to determine the feasibility and safety of transcutaneous ablation of human testicular tissue by high-intensity focused ultrasound (HIFU). Methods: Transcutaneous ablation of human testicular tissue by HIFU was performed with equipment previously developed for transrectal prostate ablation. This device utilizes a piezoceramic transducer operating at 4.0 MHz with a site-intensity of 1,600–2,000 W/cm2. To study the histological impact of transcutaneous HIFU, testes of 4 patients with prostate cancer were subjected to transcutaneous HIFU-therapy prior to scrotal orchiectomy in a phase I trial. In a phase II clinical trial, 4 patients with the typical sonographic pattern of a tumor in a solitary testis were treated with transcutaneous HIFU as a minimally invasive organ-preserving approach followed by a 6 weeks’ course of prophylactic irradiation of the testis with 20 Gy. In all 4 patients, the contralateral testis had been previously removed for testis cancer. Results: Histologically, HIFU-treated areas exhibited signs of cellular necrosis in all cases (n = 4). The border between viable and necrotic tissue was extremely sharp comprising only 5–7 cell layers. In the phase II clinical study, we aimed to ablate the entire cancer in a single therapeutic HIFU session. HIFU treatment was performed under general anesthesia. As negative side effects we observed a cutaneous thermolesion in 1 individual. One patient refused to undergo postoperative irradiation and developed a local failure. This patient underwent radical orchiectomy. Another patient received two cycles of chemotherapy for a single suspicious retroperitoneal lymph node diagnosed 6 months after HIFU therapy. Three patients are tumor-free with a follow-up of 16, 23 and 31 months, respectively. Conclusions: This study demonstrates the feasibility and safety of transcutaneous testicular tissue ablation by HIFU. Despite the major drawback of this technique, i.e. that no tumor histology is obtained, we believe that transcutaneous HIFU followed by irradiation has the potential to be established as a minimally invasive treatment alternative to organ-preserving surgery for tumors in a solitary testis.

Lower urinary tract symptoms and depression

Study Type – Symptom prevalence (cohort)

Are there symptom-specific testosterone thresholds in aging men?

Study Type – Prognosis (retrospective cohort)

Mood changes, body mass index and bioavailable testosterone in healthy men: results of the Androx Vienna Municipality Study

To determine whether sex hormones alone or in combination with body mass index (BMI) influence mood in men.

Serum Inhibin—Not a Cause of Low Testosterone Levels in Hypogonadal Prostate Cancer?

OBJECTIVES High-grade prostate cancer is associated with low serum testosterone levels, which generally recover after radical prostatectomy. The cause of this low testosterone level is unclear, and it has been hypothesized that cancer cells produce a factor that disturbs the pituitary-gonadal axis. Inhibin is a hormone that has a negative feedback effect on this axis. The aim of this study was to investigate the role of serum inhibin in patients with prostate cancer. METHODS The serum hormone levels of the pituitary-gonadal axis, including inhibin levels, in patients with prostate cancer were compared with those in patients with benign prostatic hyperplasia. Testosterone levels of less than 3 ng/mL were classified as hypogonadal. Prostate cancer was classified according to Gleason score as high grade (Gleason score 7 to 10) or low grade (Gleason score 2 to 6). RESULTS A total of 196 men (126 with prostate cancer and 70 with benign prostatic hyperplasia) were entered into the study. The serum inhibin levels did not differ significantly between the patients with benign prostatic hyperplasia and those with prostate cancer (150.0 versus 131.75 pg/mL, P = 0.062), between men with hypogonadal and eugonadal disease (143.0 versus 146.5 pg/mL, P = 0.573), or between those with low-grade and high-grade cancer (151.5 versus 146.0 pg/mL, P = 0.830). Men with high-grade cancer had lower levels of serum testosterone than did those with low-grade cancer (3.49 versus 4.09 ng/mL, P = 0.056). CONCLUSIONS The results of our study have shown that although high-grade prostate cancer is associated with low serum testosterone levels, inhibin does not appear to be the cause of this phenomenon.