Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

[New ultrasound technologies for the diagnostics of prostate cancer]. / Neue Ultraschalltechnologien für die Diagnostik des Prostatakarzinoms.

CLINICAL/METHODOLOGICAL ISSUE: Prostate cancer is the most common cancer in men. The diagnosis is based on prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasound (TRUS) guided biopsy. These techniques have considerable limitations, which result in unnecessary biopsies. Furthermore the biopsies are associated with morbidity and costs. STANDARD RADIOLOGICAL METHODS: Standard gray-scale ultrasound has a low sensitivity and specificity for prostate cancer detection. METHODOLOGICAL INNOVATIONS: New ultrasound technologies, including color- and power Doppler ultrasound, contrast enhanced US and real-time sonoelastography have shown to improve prostate cancer diagnosis. PERFORMANCE: Contrast-enhanced ultrasound has shown a sensitivity of 100% (95% CI, 95%), a negative predictive value (NPV) of 99.8% and a positive predictive value (PPV) of 88.8% for prostate cancer detection. Real-time sonoelastography has shown a sensitivity of 86%, a specificity of 81% and NPV of 91% for prostate cancer diagnosis. ACHIEVEMENTS: Most studies show that these new ultrasound modalities demonstrate a 1.5 to 2.5 times higher detection of prostate cancer per biopsy specimen compared with systematic biopsy. Multicenter studies results are at present lacking but are, however ongoing. PRACTICAL RECOMMENDATIONS: In patients with suspected prostate cancer (elevated PSA, suspicious DRE) these new ultrasound techniques should be used. These techniques can detect prostate cancer and allow a targeted biopsy approach.

Breast cancer in women: evaluation of benign and malignant axillary lymph nodes with contrast-enhanced ultrasound.

PURPOSE: We assessed the value of contrast-enhanced US for differentiating between benign and malignant axillary lymph nodes in breast cancer. MATERIALS AND METHODS: A total of 120 axillary lymph nodes in 92 patients with breast cancer were studied. All patients underwent grayscale US examination, unenhanced and enhanced color and power Doppler US, and enhanced grayscale harmonic US examination. RESULTS: The mean size of the 120 axillary lymph nodes was 1.5 cm (range 0.5 - 3.4 cm). Of all 120 axillary lymph nodes studied, 80 (67 %) were malignant and 40 (33 %) were benign according to pathological examination. The total number of vessels in baseline US did not increase between benign and malignant lymph nodes (3.3 +/- 2.2 vs. 5.4 +/- 4.0; p > 0.05). The total number of peripheral vessels was 0.5 +/- 0.8 for benign lymph nodes vs. 2.0 +/- 1.7 for malignant lymph nodes (p > 0.05). Enhanced US studies showed enhancement in both benign and malignant lymph nodes after contrast administration with a significantly higher degree of enhancement in malignant lymph nodes (p < 0.01). The total number of vessels was significantly higher in malignant lymph nodes after contrast administration (17.3 +/- 8.0 vs. 8.2 +/- 5.1, p < 0.01). Malignant lymph nodes demonstrated longer contrast enhancement duration compared to benign lymph nodes. CONCLUSION: This preliminary data shows that contrast-enhanced US can differentiate between benign and malignant lymph nodes in breast cancer.

Laparoscopic pyeloplasty.

Laparoscopic pyeloplasty must be compared with open surgery in terms of efficacy and with endopyelotomy in terms of morbidity. All of the series published so far show that the results of laparoscopic pyeloplasty equal those of open surgery. Laparoscopy is associated with a lower morbidity; therefore, it is preferable to open surgery. The morbidity of endopyelotomy is also low, at least when it is performed in a retrograde fashion. The results of endopyelotomy are poor if UPJ obstruction is caused by crossing vessels. In addition, endopyelotomy in this clinical setting carries the risk of hemorrhage. Most adults with symptomatic UPJ obstruction present with crossing vessels at the UPJ. These patients benefit from laparoscopy, and endopyelotomy should be reserved for patients with true intrinsic stenoses. For this reason, preoperative investigation using contemporary imaging techniques is of crucial importance to be able to select the most appropriate surgical method for a given patient. Laparoscopic dismembered pyeloplasty is technically feasible but difficult. The authors prefer nondismembered techniques that yield equally good results in selected patients. Nondismembered pyeloplasty as described by Fenger is easy to perform and well suited for laparoscopy.

Contrast-enhanced transrectal color doppler ultrasonography (TRCDUS) for assessment of angiogenesis in prostate cancer.

BACKGROUND: The clinical relevance of tumor angiogenesis has been investigated in several human tumors, including prostate carcinoma (PC). Previously, we found angiogenesis, measured as microvessel density (MVD), to be an independent prognostic factor in PC. Therefore, we evaluated contrast-enhanced Transrectal Color Doppler Ultrasonography (TRCDUS) for assessment of angiogenesis in PC. MATERIALS AND METHODS: We investigated 15 patients with PC before radical prostatectomy (RP) and 3 control patients before radical cystoprostatectomy. TRCDUS was performed using a micro-bubble-based ultrasound enhancer Levovist for identifying hypervascularized areas within the prostate. Computer-assisted quantification of color pixel intensity (PI) was used to evaluate objectively the hypervascularized areas; resistive index (RI) measurements were also obtained in these areas. After histopathological examination of the entire prostate gland for tumor confirmation, immunohistochemical evaluation of MVD using a polyclonal antibody against factor VIII was performed as described by Weidner et al. (N Engl J Med 324: 1-8, 1991). TRCDUS findings were correlated with the immunohistochemical data. RESULTS: All patients showed hypervascularized areas (range: 1-9) on contrast-enhanced TRCDUS. Hypervascularized areas showed a sensitivity of 50.8% and a specificity of 95.2% for detecting PC. Analysis of TRCDUS data and immunohistochemistry revealed a significant correlation between PI and MVD in PC specimens, demonstrating a correlation coefficient of r2 = 0.977 (p<0.001). RI did not correlate with MVD. CONCLUSION: Contrast-enhanced TRCDUS showed a high specificity in identifying PC. PI correlated significantly with MVD. Therefore, quantification of color Doppler signals seems to be helpful for assessment of angiogenesis in PC.

Finger injuries in extreme rock climbers. Assessment of high-resolution ultrasonography.

Dynamic high-resolution ultrasonography findings obtained in 34 extreme rock climbers with finger injuries were compared with those in 20 healthy volunteers. Thicknesses of the flexor tendon and A-2 flexor tendon pulley system were measured at the base of the proximal phalanx. The distance between the tendon and phalanx was evaluated with the finger in extension and in forced flexion as a measure of bowstringing. Gliding ability of the flexor tendons was assessed during active and passive motion. Compared with healthy volunteers, climbers showed a significantly increased thickness of the flexor tendons and the flexor tendon pulley system but no impairment of the gliding mechanism. Only in climbers did the distance between tendon and phalanx increase from 0.14 cm (+/-0.07) during extension to 0.30 cm (+/-0.09) during forced flexion. In three climbers with complete A-2 pulley ruptures this distance was up to 0.51 cm (+/-0.15) during forced flexion. Clinically unsuspected synovial cysts, thickened joint capsules, fibrous tissue, or fluid collection were found only in climbers. We concluded that dynamic ultrasonography is a valuable tool for accurate assessment of early changes in "climber's finger." It provides useful information, especially in cases where clinical evaluation is difficult, and should be performed to select appropriate therapeutic management.

[Contrast-medium enhanced reflux ultrasound in children. A comparison with radiologic imaging up to now]. / Kontrastmittelverstärkte Refluxsonographie bei Kindern. Ein Vergleich zur herkömmlichen radiologischen Untersuchungstechnik.

Voiding cystourethrography (VCUG) has long been the method of choice for the diagnosis of vesicoureteral reflux (VUR). Especially in the course of conservative treatment, the radiation dose involved might become quite high over the years. Since the development of such ultrasound echo-enhancing agents as Levovist (Schering, Germany), we now have the ability to assess the diagnostic efficacy of this agent in the evaluation of VUR with a view to replacing VCUG with the radiation-free ultrasound methodology. A total of 104 children with a mean age of 5.4 years were examined using echo-enhancing ultrasound after informed consent had been obtained from their parents. For control purposes, all children were examined by standard VCUG as well. The diagnosis of VUR was judged to be positive when microbubbles appeared in the ureter or renal pelvis. Correlations were sought between the sonographic findings and those obtained by standard VCUG. In 76 (37%) of the 208 ureter-kidney units investigated, VUR was detected by both technologies. VUR was diagnosed by ultrasonography only in 5 units and by VCUG only only in 3 units. All reflux grades (I-V) were identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 min combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. Our results clearly demonstrate that the safety and accuracy of the diagnosis of VUR by means of contrast-enhanced ultrasound is statistically comparable to those of standard radiologic VCUG. Therefore, this methodology is an exceptional approach to reducing the number of children being exposed to ionising radiation especially during conservative follow-up of children with reflux.

[Transrectal three dimensional sonography. Techniques and indications]. / Transrektale dreidimensionale Sonographie. Technik und Indikationen.

In 3-D transrectal ultrasound it is possible, for the first time, to investigate the region of interest in three planes simultaneously. Exact examination of the organs of the small pelvis as well as of pathologic changes in the region of the pelvic floor can be performed with this new imaging technique. The bulbourethral glands can be investigated routinely, which enables the diagnosis of cysts of these glands. The prostatic zones, their relations as well as the growth of the transitional zone during the development of benign prostatic hyperplasia can be visualized. Furthermore, 3-D transrectal ultrasound allows investigation of morphology and function of the rhabdosphincter. The contractility of the muscle can be quantified. 3-D ultrasound guided puncture and drainage of prostatic abscesses represents a minimally invasive therapeutic modality. This technique can be used to place needles as well as implants in the lower urinary tract. Generally, 3-D transrectal ultrasound offers new diagnostic and therapeutic possibilities.

Applications of transrectal ultrasound in prostate cancer.

Transrectal ultrasound (TRUS) was first developed in the 1970s. TRUS-guided biopsy, under local anaesthetic and prophylactic antibiotics, is now the most widely accepted method to diagnose prostate cancer. However, the sensitivity and specificity of greyscale TRUS in the detection of prostate cancer is low. Prostate cancer most commonly appears as a hypoechoic focal lesion in the peripheral zone on TRUS but the appearances are variable with considerable overlap with benign lesions. Because of the low accuracy of greyscale TRUS, TRUS-guided biopsies have become established in the acquisition of systematic biopsies from standard locations. The number of systematic biopsies has increased over the years, with 10-12 cores currently accepted as the minimum standard. This article describes the technique of TRUS and biopsy and its complications. Novel modalities including contrast-enhanced modes and elastography as well as fusion techniques for increasing the sensitivity of TRUS-guided prostate-targeted biopsies are discussed along with their role in the diagnosis and management of prostate cancer.

Focal therapy in prostate cancer-report from a consensus panel.

PURPOSE: To establish a consensus in relation to case selection, conduct of therapy, and outcomes that are associated with focal therapy for men with localized prostate cancer. MATERIAL AND METHODS: Urologic surgeons, radiation oncologists, radiologists, and histopathologists from North America and Europe participated in a consensus workshop on focal therapy for prostate cancer. The consensus process was face to face within a structured meeting, in which pertinent clinical issues were raised, discussed, and agreement sought. Where no agreement was possible, this was acknowledged, and the nature of the disagreement noted. RESULTS: Candidates for focal treatment should have unilateral low- to intermediate-risk disease with clinical stage

[The value of real-time elastography in the diagnosis of prostate cancer]. / Die Wertigkeit der Echtzeitelastographie in der Diagnostik des Prostatakarzinoms.

Randomized biopsy sampling under transrectal ultrasound (TRUS) guidance is the gold standard for the diagnosis of prostate cancer. In addition improvements in the quality of conventional ultrasound, new methods that complement conventional TRUS are opening the door to earlier and better targeted diagnosis of prostate cancer. One of these new methods is sonoelastography. Its impact on prostate cancer diagnostics has not yet been fully investigated, but the number of publications on this new technique indicate increasing interest in it.

Sonographic measurement of renal pelvis wall thickness as diagnostic criterion for acute pyelonephritis in adults.

PURPOSE: Inflammatory processes may increase the urothelial thickness of the renal pyelon. Purpose of the study was to assess sonographic measurement of pyelon wall thickness (PWT) in adult patients with acute pyelonephritis, chronic urinary tract infection (UTI) and indwelling ureteral stents. MATERIALS AND METHODS: Four study groups (acute pyelonephritis n=50, chronic UTI n=10, indwelling ureteral stents n=10, controls n=25) underwent renal ultrasonography (Acuson Seqouia, Mountain View, CA; 6 MHz Transducer). The renal pyelon was imaged in transverse and longitudinal planes. PWT measurements of patients with acute pyelonephritis were repeated after successful antibiotic treatment. RESULTS: Mean PWT in healthy controls was 1.0 mm+/-0.19. In patients with acute pyelonephritis, PWT was significantly increased to 2.9 mm+/-0.89 (p<0.001). PWT decreased significantly after antibiotic treatment to 1.4 mm+/-0.47 (p<0.001). Kidneys with indwelling stents presented with a PWT of 2.7 mm+/-0.68, kidneys with chronic UTI demonstrated a PWT of 2.8 mm+/-0.62. PWT in these patient groups was significantly greater than PWT in healthy volunteers (p<0.001). The interobserver agreement was excellent (p<0.001). CONCLUSION: PWT is a reproducible diagnostic criterion for acute pyelonephritis. Based upon our experience, we suggest a cut-off value of 2.0 mm to distinguish healthy kidneys from those with urothelium thickened by inflammation. PWT cannot be used to distinguish acute pyelonephritis from chronic inflammation of the urothelium.

Transurethral ultrasonography-guided injection of adult autologous stem cells versus transurethral endoscopic injection of collagen in treatment of urinary incontinence.

In the last years preclinical studies have paved the way for the use of adult muscle derived stem cells for reconstruction of the lower urinary tract. Between September 2002 and October 2004, 42 women and 21 men suffering from urinary stress incontinence (age 36-84 years) were recruited and subsequently treated with transurethral ultrasonography-guided injections of autologous myoblasts and fibroblasts obtained from skeletal muscle biopsies. The fibroblasts were injected into the urethral submucosa, while the myoblasts were implanted into the rhabdosphincter. In parallel, 7 men and 21 women (age 39-83 years) also diagnosed with urinary stress incontinence were treated with standard transurethral endoscopic injections of collagen. Patients were randomly assigned to both groups. After a follow-up of 12 months incontinence was cured in 39 women and 11 men after injection of autologous myoblasts and fibroblasts. Mean quality of life score (51.38 preoperatively, 104.06 postoperatively), thickness of urethra and rhabdosphincter (2.103 mm preoperatively, 3.303 mm postoperatively) as well as contractility of the rhabdosphincter (0.56 mm preoperatively, 1.462 mm postoperatively) were improved postoperatively. Only in two patients treated with injections of collagen incontinence was cured. The present clinical results demonstrate that, in contrast to injections of collagen, urinary incontinence can be treated effectively with ultrasonography-guided injections of autologous myo- and fibroblasts.

Comparison of contrast enhanced color Doppler targeted biopsy to conventional systematic biopsy: impact on Gleason score.

PURPOSE: Prostate cancer grading with Gleason score is an important prognostic factor. This prospective randomized study compares ultrasound systematic biopsy vs contrast enhanced color Doppler targeted biopsy for the impact on Gleason score findings. MATERIALS AND METHODS: We examined 690 men (mean age 56 years, range 41 to 77) with a serum total prostate specific antigen of 1.25 ng/ml or greater, a free-to-total prostate specific antigen ratio less than 18% and/or a suspicious digital rectal examination. Contrast enhanced color Doppler targeted biopsies with a limited number of cores (5 or less) were performed in hypervascular areas of the peripheral zone during administration of the ultrasound contrast agent Sonovuetrade mark (Bracco, Milano, Italy). Ten systematic biopsies were obtained in a standard spatial distribution. Cancer detection rates and Gleason score were compared. RESULTS: Prostate cancer was identified in 221 of 690 subjects (32%) with a mean prostate specific antigen of 4.6 ng/ml (range 1.4 to 35.0). Prostate cancer was detected in 180 of 690 subjects (26%) with contrast enhanced color Doppler targeted biopsy and in 166 of 690 patients (24%) with systematic ultrasound biopsy. The Gleason score of all 180 cancers detected on contrast enhanced color Doppler targeted biopsy was 6 or higher (mean 6.8). The Gleason score of all 166 cancers detected on systematic biopsy ranged from 4 to 6 and mean Gleason score was 5.4. Contrast enhanced color Doppler targeted biopsy detected significantly higher Gleason scores compared to systematic biopsy (Wilcoxon rank sum test p <0.003). CONCLUSIONS: Contrast enhanced color Doppler targeted biopsy detected cancers with higher Gleason scores and more cancer than systematic biopsy. Therefore, contrast enhanced color Doppler seems to be helpful in the grading of prostate cancer, which is important for defining prognosis and deciding treatment.

Isolated right-sided varicocele as a salvage pathway for portal hypertension.

Retrograde blood flow can occur in the testicular veins and in the pampiniformis plexus in the absence of valves or if the valves are incompetent, resulting in tortuosity and dilatation of the veins. These abnormal alterations in the anatomy of the veins, termed varicoceles, are associated with infertility in the male. Most varicoceles occur on the left. We report the case of a rare isolated right-sided varicocele in a male evaluated for infertility in whom extensive work-up revealed venous anomalies and a spontaneous porto-systemic shunt. In such cases, standard approaches to infertility treatment are fruitless.

Vascular damage induced by type 2 diabetes mellitus as a risk factor for benign prostatic hyperplasia.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the relationship between benign prostatic hyperplasia (BPH) and arteriosclerosis shown in a model of type 2 diabetes in a trans-sectional population study using contrast-enhanced colour Doppler ultrasound for exact assessment of prostatic blood flow. METHODS: Contrast-enhanced transrectal colour Doppler ultrasound was performed using a microbubble-based ultrasound enhancer SonoVue for evaluating prostate vascularity (transitional zone [TZ] and peripheral zone [PZ]) in diabetic BPH patients, non-diabetic BPH patients and healthy subjects. Computer-assisted quantification of colour pixel intensity (CPI) was used to objectively evaluate the prostate vascularity. Resistive index measurements were obtained in the TZ and the PZ. Findings were compared between these three groups. RESULTS: TZ-CPI was significantly lower in diabetic patients than in non-diabetic BPH men (p=0.001), whereas the CPI of the PZ showed no difference between these two groups (p=0.978). TZ-CPI of patients with diabetic and non-diabetic BPH were significantly lower than in controls (p<0.001), but no difference was found between diabetic and healthy patients in the PZ (p=0.022) and borderline significance was seen when comparing patients of the BPH group with the control patients (p=0.019). Resistive index values of the TZ in diabetic patients showed significantly higher values (p<0.001) than the BPH and control groups. CONCLUSIONS/INTERPRETATION: The significantly lower CPI and higher resistive index values of the TZ in diabetic patients compared with patients with non-diabetic BPH and healthy subjects indicate considerable vascular damage in the TZ of these patients. Diabetic vascular damage may cause hypoxia and may contribute to the pathogenesis of BPH.

[Ultrasound contrast agents and prostate cancer]. / Ultraschallkontrastmittel und Prostatakarzinom.

Prostatic carcinoma is the most frequent malignant disease in men and associated with very high mortality. The diagnostic work-up of prostatic carcinoma is based on tests to determine the level of prostate-specific antigen (PSA), digital rectal examination, and transrectal sonography. Due to diagnostic limitations, ultrasound-guided prostate biopsy is the method of choice for diagnosis of prostatic carcinoma. New imaging technologies allow detection of prostatic carcinoma, thus facilitating removal of specific biopsy specimens from these regions. Introduction of ultrasound contrast agents ("echo signal enhancers") significantly increased the diagnostic potential of this method, making it possible to visualize tumor vascularization.

Subclinical microtraumatisation of the scrotal contents in extreme mountain biking.

Mountain bikers had a high frequency of extratesticular and testicular disorders, which were associated with clinical symptoms in half the bikers. Hence a high rate of repeated microtraumatisation of the scrotal contents must be assumed.

US findings in the scrotum of extreme mountain bikers.

PURPOSE: To sonographically investigate whether mountain bikers have a higher prevalence of scrotal abnormalities compared with that in nonbikers. MATERIALS AND METHODS: Eighty-five male mountain bikers (mean age, 25 years; age range, 17-45 years) and 31 healthy nonbikers (mean age, 24 years; age range, 15-37 years) were examined for scrotal findings at ultrasonography (US). Only male subjects with a history of extensive off-road biking (> or =2 h/d 6 d/wk; covered distance, >5,000 km/y) were assigned to the group of mountain bikers, whereas the control group did not engage in bicycling. In addition to clinical evaluation, US examination of the scrotum was performed by using a linear-array transducer operating at a frequency of 8.0 MHZ: RESULTS: Eighty (94%) mountain bikers had abnormal findings at scrotal US. Thirty-nine (46%) had a history of intermittent scrotal tenderness or discomfort but no severe scrotal trauma. Abnormal findings at US included scrotal calculi in 69 (81%), epididymal cysts in 39 (46%), epididymal calcifications in 34 (40%), testicular calcifications in 27 (32%), hydroceles in 24 (28%), varicoceles in nine (11%), and testicular microlithiasis in one (1%). In the control group, abnormal findings were noted in five (16%), all of whom had epididymal cysts. The overall difference in the number of scrotal abnormalities in bikers compared with the number in nonbikers was significant (P <.0001, chi2 test). CONCLUSION: US shows a significantly higher prevalence of extratesticular and testicular disorders in these mountain bikers compared with nonbikers.

Detection of prostate cancer with a microbubble ultrasound contrast agent.

The diagnosis of prostate cancer is currently limited by the low sensitivity and specificity of systematic conventional grey-scale ultrasonography. We assessed contrast-enhanced colour Doppler ultrasonography by means of a microbubble ultrasound contrast agent to detect tumour vascularity and improve the diagnosis of prostate cancer. The use of a microbubble ultrasound contrast agent for transrectal colour Doppler targeted biopsy significantly improved the detection of prostate cancer compared with systematic biopsy following conventional grey-scale ultrasonography (p<0.001). Contrast-agent enhanced colour Doppler imaging may allow for limited targeted biopsies (five or less), which reduces costs and morbidity.