Sonohistology - ultrasonic tissue characterization for prostate cancer diagnostics.

A computer-aided diagnostic system for imaging prostate cancer has been developed in order to supplement today's conventional methods for the early detection of prostate carcinoma. The system is based on analysis of the spectral content of radiofrequency ultrasonic echo data in combination with evaluations of textural, contextual, morphological and clinical features in a multiparameter approach. A state-of-the-art, non-linear classifier, the so-called adaptive network-based fuzzy inference system, is used for higher-order classification of the underlying tissue-describing parameters. The system has been evaluated on radio-frequency ultrasound data originating from 100 patients using histological specimens obtained after prostatectomy as the gold standard. Leave-one-out cross-validation over patient data sets results in areas under the ROC curve of 0.86 +/- 0.01 for hypoechoic and hyperechoic tumors and of 0.84 +/- 0.02 for isoechoic tumors, respectively.

[Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the renal parenchyma under aspirin use. Electron microscopic findings in the rat kidney]. / Ultrastrukturelle Veränderungen am Nierenparenchym durch ESWL unter Acetylsalicylsäure (ASS). Elektronenmikroskopische Befunde an der Rattenniere.

BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma-inducing mechanism has not been understood completely at the ultrastructural level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats (n=24) was investigated in an experimental setting using a special ESWL device. Ultrastructural examination was performed by light-, transmission electron- and scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared in all kidneys independently of aspirin intake. Endothelial detachment, lethal cell injury, gaps and mechanical disruption of the glomerular basement membrane were regularly found. After 1 week, repair processes were completed with evidence of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma a second ESWL should not be performed within 1 week of the first treatment.

[Prostate cancer diagnosis using ultrasound elastography. Introduction of a novel technique and first clinical results]. / Prostatakarzinomdiagnostik durch UltraschallelastographieVorstellung eines neuartigen Verfahrens und erste klinische Ergebnisse.

During the last decade screening has improved prostate cancer detection. The main reason for this development is a better understanding of the margins of prostate-specific antigen (PSA) serum levels and the classification of PSA subtypes. In contrast, the introduction of transrectal ultrasound has not led to a measurable change in the prostate cancer detection rate. Our aim was to develop a novel ultrasound system for the acquisition of elastographic images of the prostate and evaluate the system regarding its clinical applicability. We used a technically modified conventional ultrasound system and analyzed the high-frequency ultrasonic data with a computer program. The first patient-based results suggest that elastography allows an accurate measurement of tumor size and localization in contrast to conventional transrectal ultrasound. Elastography visualizes different tissue elasticities to distinguish benign and cancerous tissue. Thus, we were able to even correctly classify prostate cancer lesions which are iso- or hyperechoic in B-mode sonography.

Ultrasonic tissue characterization for prostate diagnostics: spectral parameters vs. texture parameters.

An ultrasonic multi-feature tissue characterizing system for the detection of prostate cancer is presented. The system is based on the processing of radio frequency (RF) ultrasonic echo data. Data from 100 patients was acquired in a clinical study. Parameters are extracted from the RF echo data and classified using two adaptive network-based fuzzy inference systems (FIS) working in parallel as a nonlinear classifier. Next to spectral parameters, conventional texture parameters are calculated using demodulated and log-compressed echo data. In the first approach, the classifier is trained on both, spectral and texture parameters. In the second approach, the classifier is only trained on texture parameters. Classification results of both approaches are compared and it is demonstrated, that only the use of spectral parameters yields satisfying classification results. Results of a minimum distance classifier (MDC) are presented for comparison with the fuzzy inference system. For the final fuzzy inference systems used in this approach, the area under the ROC curve is between 84% and 86% for the combined approach and between 70% and 74% for the approach based on texture parameters only.

[Postoperative pain therapy in urology. A prospective study]. / Postoperative Schmerztherapie in der Urologie. Eine prospektive Studie.

A sufficient analgesic treatment in the early postoperative period is important for the patients comfort level. Moreover, physical therapy for prophylaxis of pneumonia and thrombosis is better tolerated. In a prospective study, we compared two postoperative pain management regimens to establish a sufficient pain management without the need of additional costs or manpower. Of 215 patients undergoing major urologic surgery, 111 patients received on demand medication exclusively (group 1), whereas 104 patients were treated with basic analgesics combined with on demand medication (group 2). Pain intensity, side effects and subjective well being were evaluated with a visual analogue scale and a standardised interview. Pain intensity and side effects were significantly lower in group 2. Thus, with combined analgesic treatment, postoperative pain relieve can be achieved safely and without additional costs.

Particle migration after transurethral injection of carbon coated beads for stress urinary incontinence.

PURPOSE: Despite 20 years of experience with injectable bulking agents for stress urinary incontinence results are rather disappointing. The satisfying initial results of collagen injection are rapidly decreasing with time, whereas synthetic bulking agents have shown problems with migration and biocompatibility. The ideal bulking agent would be permanent with a good clinical long-term success rate. We report our experience with Durasphere (Carbon Medical Technologies, Inc., St. Paul, Minnesota), a new injectable bulking agent containing carbon coated beads. MATERIALS AND METHODS: Seven men and 13 women with a mean age of 62.5 years underwent transurethral submucosal injection. The 13 female patients had been diagnosed with type III stress urinary incontinence and each had undergone at least 1 unsuccessful previous operation for urinary incontinence. There were iatrogenic and traumatic sphincter lesions in 6 and 1 of the male patients, respectively. Mean volume injected per treatment was 6.0 cc. Mean followup was 10 months. RESULTS: After 6 months 76.9% of the female patients were improved but after 12 months the success rate decreased to 33%. In the male patients after 6 months the success rate was 66%, which decreased to 33% after 12 months. At the 6-month followup we observed significant migration of the carbon coated beads into the local and distant lymph nodes as well as into the urethral mucosa. CONCLUSIONS: Due to limited success and proved particle migration, carbon coated beads do not show any improvement over existing bulking materials. The clinical effect of bead migration must be determined before extended use of this substance.

Male lower urinary tract symptoms and related health care seeking in Germany.

OBJECTIVES: To investigate the prevalence of lower urinary tract symptoms (LUTS) and LUTS- related health care issues in the male population between the ages of 50 and 80 in Germany. METHODS: 8,973 randomly chosen men in the age group of interest received by mail a self-administered questionnaire addressing voiding symptoms and bother, common health status, and social demographic as well as health care resources related issues. RESULTS: Of 6,031 (67.2%) returned questionnaires, 5,404 (60.2%) were properly filled out and entered into the database. Of these, 5,004 (56%) completed all IPSS questions. 3,539 (70.7%) of the men presented with no or mild LUTS (IPSS 0--7), 1,465 (29,3%) with moderate to severe voiding symptoms (IPSS >7), respectively. From logistic regression analysis it appears that mainly bother from voiding symptoms as well as incomplete emptying and week stream induced a visit to the doctor. Of men with moderate symptoms (IPSS 8--19), 40% did not report any bother. CONCLUSION: LUTS is a common condition among German elderly males. In general, bother from LUTS seem to have more effects on health care seeking behavior than symptoms themselves or physical health status. Bother scores may discriminate between those individuals with moderate symptoms (IPSS 8--19), who may be followed through watchful waiting instead of active therapy.

Idiopathic calcification of the seminal vesicles: a rare cause for prostate cancer overstaging.

Calcification of the seminal vesicles is a rare phenomenon. We present 2 cases in whom calcification of the seminal vesicles led to preoperative overstaging of prostate cancer. Although idiopathic calcifications are extremely rare, calcifications appear more frequently in diabetic patients. Therefore, knowledge of these formations is essential to prevent overstaging, namely infiltration of the seminal vesicles.

Urodynamic and rectomanometric findings in patients with spinal cord injury.

Patients with spinal cord lesion suffer from complex disorders of bladder and anorectal function. We assessed the value of urodynamics and anorectal manometry as prognostic and diagnostic tools in these patients and evaluated the usefulness of these techniques for the differentiation between complete and incomplete spinal cord lesions. Thirty patients with suprasacral spinal cord injury (six women, 24 men; mean age, 31 years) underwent anorectal manometry and urodynamics within the first 40 days after injury. The findings were compared to the results of a clinical neurologic evaluation. Fifteen patients were classified as complete lesions on their clinical signs, three of these lesions were incomplete according to urodynamic testing and five were incomplete according to visceral sensory testing by anorectal manometry. Despite significant differences in maximum bladder capacity (589 versus 465 mL), maximum detrusor pressure (18 versus 31 cm H2O) was not significantly different between patients with complete and patients with incomplete spinal cord injury. Anorectal manometry did not reveal any significant differences in resting pressure, abdominal pressure, and maximal rectum volume between these groups. Urodynamics and anorectal manometry may be superior to neurologic assessment of completeness of spinal cord lesions. Urodynamics and anorectal manometry were not helpful in the prediction of onset or severity of detrusor hyperreflexia. Thus, we do not regard anorectal manometry as a standard diagnostic tool in spinal cord injury patients.

Effect of beta-sitosterol on transforming growth factor-beta-1 expression and translocation protein kinase C alpha in human prostate stromal cells in vitro.

BACKGROUND: Today, plant extracts are widely used in the treatment of benign prostatic hyperplasia (BPH). However, the complete mode of action of the active substance, beta-sitosterol, is under investigation. The purpose of this study was to investigate the effect of beta-sitosterol on the expression of transforming growth factor beta 1 (TGF-beta1) and the activity of protein kinase C alpha (PKC-alpha) in primary prostate stromal cell cultures in vitro. METHODS: Tissue samples for primary cell cultures were obtained from patients undergoing transurethral resection of the prostate (TURP). TGF-beta1 levels in stromal cell conditioned media following a culture with beta-sitosterol were detected in a TGF-beta1 specific ELISA assay. Following different incubation periods with beta-sitosterol, cells were lysed and fractionated into a Triton-soluble membrane fraction and a cytosol fraction. PKC-alpha protein was detected using immunoblot analysis. RESULTS: Beta-sitosterol was able to induce the expression and secretion of TGF-beta1 significantly between 1.26- and 1.86-fold compared to a cholesterol and the nonsupplemented control in 6 of 8 individual cultures. The total amount of secreted TGF-beta1 varied in cells from different patients. Based on its presence in both membrane fraction and cytosol, PKC-alpha appeared to be constitutively expressed in stromal cells. In the absence of beta-sitosterol PKC-alpha was predominantly found in its membrane-associated active form. Following a culture with beta-sitosterol, a translocation of PKC-alpha from the membrane to the cytosol was observed. This effect was specific for beta-sitosterol as compared to cholesterol. CONCLUSION: This study describes the effect of beta-sitosterol on the expression of a multifunctional growth factor (TGF-beta1) and the activity of PKC-alpha membrane in stromal cells of the human prostate in vitro.

Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18-month follow-up.

OBJECTIVES: To determine the long-term effects of phytotherapy with beta-sitosterol (the trade name for beta-sitosterol used in this study is Harzol(R)) for symptomatic benign prostatic hyperplasia (BPH). Patient and methods At 18 months after enrolment in a 6-month multicentre double-blind placebo-controlled clinical trial with beta-sitosterol (reported previously), patients were re-evaluated using the modified Boyarsky score, the International Prostate Symptom Score and quality-of-life index, the maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR). In this open extension of the original trial (after 6 months of treatment or placebo), patients were free to chose their further treatment for BPH. RESULTS: In all, 117 patients (59%) were eligible for analysis during the follow-up. Of the formerbeta-sitosterol group, 38 patients who continued beta-sitosterol treatment had stable values for all outcome variables between the end of the double-blind study and after 18 months of follow-up. The 41 patients choosing no further therapy had slightly worse symptom scores and PVR, but no changes in Qmax. Of the former placebo group, 27 patients who started beta-sitosterol after the double-blind trial improved to the same extent as the treated group for all outcome variables. The 18 patients choosing no further therapy showed no signs of improvement. CONCLUSION: The beneficial effects of beta-sitosterol treatment recorded in the 6-month double-blind trial were maintained for 18 months. Further clinical trials should be conducted to confirm these results before concluding that phytotherapy with beta-sitosterol is effective.

[Ultrasound elastography of the prostate. A new technique for tumor detection]. / Ultraschall-Elastographie der Prostata. Ein neues Verfahren für die Tumorerkennung.

AIM: Prostate tumours are often of harder consistency than the surrounding tissue. During digital rectal examination, this fact can be used not only to detect hypertrophy but also localized hardenings. The examination by digital palpation is inaccurate and, even in combination with PSA-value and a transrectal ultrasonic examination, the result is often not reliable. Ultrasound elastography enables us to measure and visualize the elastic properties of a tissue region and is a useful supplement to the examination by digital palpation. Ultrasound elastography is able to measure and visualize the elastic properties of a tissue region, therefore it is a useful supplement to commonly used diagnostic procedures. METHOD: We have developed a new system for elastographic prostate diagnosis which can be used during the transrectal ultrasonic examination. During the examination a sequence of ultrasonic images is acquired while the organ is slightly compressed by the ultrasound probe. Using numerical analysis of image pairs for the acquired sequence we calculate the tissue strain which represents the spatial elasticity distribution of a specific cross-section of the organ. This enables us to distinguish hard areas in the tissue. Image artifacts resulting from lateral motion components, i.e., orthogonal to the direction of the applied force, are compensated for by a special approach. RESULTS: We present results obtained from a typical elastography phantom and also the first in vivo images from patients who were undergoing radical prostatectomy. Our images prove that ultrasound elastography has the potential to detect malignant tissue areas, which are inconspicuous in the B-mode image. Our findings are confirmed by the corresponding histological specimens.

Combined intravesical and oral oxybutynin chloride in adult patients with spinal cord injury.

OBJECTIVES: Detrusor hyperreflexia with elevated storage pressures presents a major risk factor for renal damage in patients with neurogenic lower urinary tract dysfunction. If standard anticholinergic treatment is unsuccessful, surgical treatment must be considered. We evaluated the effects of intravesical oxybutynin treatment on detrusor hyperreflexia in patients in whom standard oral treatment had failed. METHODS: Twenty-five patients (mean age 36. 7 years) with storage pressures greater than 40 cm H(2)O despite standard anticholinergic treatment received intravesical (15 mg three times daily) and oral oxybutynin chloride treatment. The follow-up evaluations included urodynamic testing, renal ultrasound, urine examination (urinalysis and urine culture), and evaluation of side effects. RESULTS: The mean follow-up was 6 months. Intravesical treatment led to an increase in bladder storage volume from 349 to 420 mL. The mean maximum storage pressure was significantly reduced from 54 to 26.5 cm H(2)O. Detrusor storage pressures returned to values less than 40 cm H(2)O in 21 of 25 patients. Dysreflexia was treated successfully in 3 of 5 patients. No patient developed renal damage. No severe side effects or drug-related discontinuation of treatment were observed. CONCLUSIONS: Intravesical oxybutynin therapy seems to be a safe and effective treatment option for detrusor hyperreflexia in adults and avoids surgical treatment in most patients. Long-term observations concerning side effects, acceptance, and efficacy are needed.

Suramin treatment in hormone- and chemotherapy-refractory prostate cancer.

OBJECTIVES: Suramin, a polysulfonated naphtylurea with anti-growth factor activity, was used in the treatment of metastatic, hormone- and chemotherapy-refractory prostate cancer. Recent studies have proved the effect of suramin on prostate cancer. METHODS: Between March 1990 and January 1994, 27 patients with metastatic prostate cancer were enrolled in this study. Treatment regimen consisted of a loading phase, allowing patients to reach suramin serum levels between 180 and 250 microg/mL using a suramin dose of 1.4 g/m2 at 3-day intervals. Constant suramin serum levels were maintained by a 0.5 to 1-g/m2 dose every 7 to 10 days. Because previous studies showed suramin to have serious toxicity, compromised organ status was excluded by repeated examinations. RESULTS: Six patients did not complete the suramin loading phase because of side effects and were removed from the study. With an average cumulative suramin dose of 14.2 g, 33% of the assessable patients (7 of 21) experienced a more than 50% reduction of prostate-specific antigen (PSA) and/or alkaline phosphatase (AP) serum levels. Mean survival in these suramin-responsive patients was 495 days. Two of these patients experienced a remarkable reduction of metastases in bone scan examinations. Another 48% of the patients (10 of 21) had essentially unchanged AP and PSA serum levels during suramin treatment, indicating stable disease. Mean survival of these patients was 341 days. In 4 patients undergoing suramin treatment, continuous clinical progression of the disease was observed (mean survival 79 days). Toxicity was less or comparable to prior reported studies; the most common side effects were polyneuropathy, allergic skin rash, and vortex keratopathy. CONCLUSIONS: Suramin has limited, but significant, efficacy even in chemotherapy- and hormone-refractory prostate cancer, without serious toxicity.

Tissue-characterization of the prostate using radio frequency ultrasonic signals.

In this paper, we will present a complete method and system for the detection of prostatic carcinoma, providing color-coded images of the estimated probability of malignancy by processing radio-frequency ultrasonic echo signals. For this, a hardware setup based on a conventional diagnostic sonograph was realized. The image-processing software works on ultrasound images automatically segmented into regions of about 3x3.5 mm. System-dependent effects, as well as tissue attenuation, were measured and compensated for. Tissue-characterisation parameters, which have been used successfully by other authors, were calculated for each segment. To demonstrate the methods of selection of relevant parameters and comparison of different classifiers, a first clinical study using data of 33 patients with local prostatic carcinoma was performed. For these patients, location and extent of the carcinoma were known from histological findings after radical prostatectomy. Classifiers investigated during the study were: the linear and quadratic Bayes classifier, a nearest neighbor classifier, and several classifiers based on Kohonen-maps. The best classifier was used to calculate color-coded result images. Applying a threshold of 50% to the estimated probability of malignancy, produced the encouraging results of 82 and 88% for sensitivity and specificity, respectively.

A new system for the acquisition of ultrasonic multicompression strain images of the human prostate in vivo.

We describe a novel recording system for the acquisition of multicompression strain images of the human prostate in vivo. The force at the tip of an ultrasonic transrectal probe is measured continuously, and ultrasonic RF-images are acquired consecutively at specified levels of compression. The acquired image sequence is processed by conventional cross-correlation techniques to obtain time shift estimates and corresponding strain images. We present phantom measurements as well as in vivo results and discuss the advantages and restrictions of the proposed system.

Species differences in the glutathione transferase GSTT1-1 activity towards the model substrates methyl chloride and dichloromethane in liver and kidney.

Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

History of urinary diversion.

In 1852, Simon was the first to describe a urinary diversion using intestinal segments. In the late 19th and early 20th century, in the absence of antibiotics, urinary diversion using bowel segments carried a high risk of peritonitis. When Coffey introduced a new method for ureteric implantation in 1911, ureterosigmoidostomy became the most frequently used technique. The ileal conduit, first described by Zaayer in 1911, was established as a standard technique by Bricker in 1950. At the same time, Ferris and Oedel demonstrated a hyperchloremic metabolic acidosis in 80% of the patients with ureterosigmoidostomy, and the ileal conduit became the preferred from of urinary diversion. The first attempts to create a continent urinary diversion were undertaken by Tizzoni and Foggi in 1888. Mauclaire, in 1895, used the isolatec rectum as a urinary reservoir. Two findings were essential for the development of modern continent urinary diversion: Kock established the principle of bowel detubularization to create a low-pressure reservoir, and Lapides popularized the use of clean intermittent catheterization. Utilizing these techniques, a variety of continent reservoirs were introduced. The majority of these used either ileal segments, like the Hautmann neobladder, or ileocecal segments, like 'Le Bag'. Sinaiko was the first to use the stomach for the creation of a urinary reservoir in 1956. Continent urinary diversion is the method of choice in a large number of patients today. Experimental work demonstrated that the creation of a new bladder using cultured urothelial and muscle cells with biodegradable polymers as a scaffold is feasible, and future developments may be vastly influenced by these techniques.