Complete high-intensity focused ultrasound in prostate cancer: outcome from the @-Registry.

BACKGROUND: To analyze data on patients with localized prostate cancer who were treated with complete high-intensity focused ultrasound (HIFU) prospectively captured within a voluntary HIFU user database (@-Registry). METHODS: The @-Registry includes data from consecutive patients treated with Ablatherm (EDAP-TMS) HIFU at nine European Centres during the period 1994 and 2009. For this analysis, the data repository was reviewed for information on patients with localized prostate cancer (T1 -- T2) treated with complete (whole-gland) HIFU on the basis of an anterior-posterior prostate height of ≤24 mm and a treated volume >120% of the prostate volume. Patients were regularly followed with PSA measurement and biopsy. Biochemical failure was defined for this study as PSA nadir +2 ngml(-1) (Phoenix definition). Disease-free survival was based on a biopsy, retreatment and biochemical data. Patients were risk group-stratified using the D'Amico classification system. RESULTS: The median follow-up was 2.8 years for the 356 patients included in the analysis. The majority could be classified as either low (44.9%) or intermediate risk (39.6%); 14.6% patients were classified as high risk. The median (mean, s.d.) PSA nadir was 0.11 ng ml(-1) (0.78 and 3.6), achieved at a mean (s.d.) of 14.4 (11.6) weeks after HIFU. Follow-up biopsies on 226/356 (63.5%) patients revealed an overall negative biopsy rate of 80.5% (182/226); there was no statistically significant difference in positive biopsy rate by risk group-stratification. Actuarial freedom from biochemical recurrence at 5 and 7 years according to the Phoenix definition was 85% and 79%, respectively. Disease-free progression rates at 5 and 7 years were 64% and 54%, respectively. CONCLUSIONS: Whole-gland prostate HIFU as primary monotherapy for localized prostate cancer achieves a recurrence-free survival in short-term analysis as assessed by prostate biopsy and serum PSA endpoints in a majority of patients.

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

[Transrectal high-intensity focused ultrasound for local treatment of prostate cancer. 2009 Update]. / Hoch intensiver fokussierter transrektaler Ultraschall (rHIFU) zur lokalen Therapie des Prostatakarzinoms. Update 2009.

Pulsed robotic high-intensity focused ultrasound (rHIFU) is an interesting therapeutic option mainly due to its noninvasive character. In urologic oncology, rHIFU is used for the transrectal therapy of prostate cancer. While percutaneous therapy of renal cancer using rHIFU is still being tested in experimental studies, transrectal therapy with rHIFU for prostate cancer is already established in more than 230 urologic departments worldwide. The results of prostate cancer therapy with rHIFU are mainly based on different clinical studies. In 2007 a clinical study comparing rHIFU and cryotherapy for the treatment of prostate cancer was initiated in the USA in order to gain clinical approval by the FDA. The most recent publications concluded that the use of rHIFU is an effective standard treatment for prostate cancer with a broad range of indications in all tumor stages: (1) in the primary treatment of local prostate cancer, (2) in patients with local recurrence after failure of any primary treatment, and (3) as an adjuvant therapy in the palliation of systemic prostate cancer.

[HIFU in urological oncology]. / HIFU in der Uro-Onkologie.

The growing interest in high-intensity focused ultrasound (HIFU) technology is mainly due to its many potential applications as a new energy source and as noninvasive therapy. It has been introduced to urological oncology as a transrectal treatment for prostate cancer and as extracorporeal treatment for kidney cancer. Although its application in the kidney is still at the clinical feasibility phase, HIFU technology is currently being used in daily practice in Europe for the treatment of prostate cancer. Reports in the literature describing results of HIFU for prostate cancer are mainly based on monocentric, prospective clinical studies. The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and moderately differentiated tumors, as well as for local recurrence after external beam radiation. Two different devices for transrectal treatment of prostate cancer are available, which are essentially different in technology, application mode, published results, and side effects.HIFU in locally recurrent cancer after surgery, as well as adjuvant HIFU for local debulking in locally advanced or metastatic disease, shows promising first results for reducing local disease-induced morbidity and for delay of progression.

[Local recurrence of prostate cancer after curative therapy. HIFU (Ablatherm) as a treatment option]. / Das Lokalrezidiv des Prostatakarzinoms nach kurativer Therapie. Therapieoption HIFU (Ablatherm).

In terms of effectivity and impact, no ideal approach is as yet available for treatment of local recurrence of prostate cancer. We direct our attention mainly toward high-intensity focused ultrasound (HIFU). HIFU therapy (Ablatherm) is only performed in our department when the following criteria are met: the recurrent tumor must be visualizable with imaging procedures (for HIFU, transrectal ultrasound is employed), the tumor must be accessible to the scanner head (penetration depth: 25 mm), and finally the diagnosis of recurrent tumor has to be histologically confirmed. An indisputable advantage of HIFU is the option of easily administering HIFU therapy for a second time in the presence of tumor remnants or in the event of cancer recurrence. Depending on the primary cancer treatment given, salvage HIFU achieves a biopsy-proven tumor-free state in 60-74% of patients. These results are in line with those that can be obtained with other salvage strategies (radical prostatectomy, radiation therapy). However HIFU shows reduced postoperative morbidity with less side effects.

The isolated perfused kidney: an in vitro test system for evaluation of renal tissue damage induced by high-energy shockwaves sources.

Most of our knowledge of shockwave-induced renal damage is based on animal experiments and clinical observation. We developed a tissue model using isolated porcine kidneys perfused with Berliner Blau dye in physiologic saline using a Ureteromat Perez-Castro peristaltic pump connected to the renal artery. Reproducible results were obtained under a variety of experimental conditions. Further refinements of the model might consist of interposition of tissue layers in the shockwave path or simulation of ventilatory movements.

Results and side effects of high-intensity focused ultrasound in localized prostate cancer.

At the time of diagnosis, prostate cancer is organ confined in 70% of the cases. A quarter of these patients undergo local therapy (surgery/radiation); 75% risk disease progression by "watchful waiting" or systemic side effects through hormonal ablation. Local high-intensity focused ultrasound (HIFU), as minimal invasive tissue coagulation (85 degrees C), ablates prostatic tissue with high precision. Since April 1996, 184 patients have undergone 232 sessions of transrectal HIFU therapy (average 90 min) under spinal anesthesia at 2.25/3.0 MHz, 50 W, and a penetration depth of 25 mm. The follow-up serum prostate specific antigen (PSA) concentration, sextant biopsies, International Prostate Symptom Score (IPSS), quality of life measures (QoL), and complaint registration provide the foundation for this clinical evaluation. Follow-up sextant biopsies (an average of 1.9) showed 80% of the patients to be cancer free. In men with residual cancer, the tumor mass was reduced more than 90%. The PSA nadir in 97% was <4 ng/mL, including 61% with values <0.5 ng/mL. After primary HIFU, no severe side effects (fistula, second or third grade incontinence, rectal mucosal burns) occurred. All patients had a suprapubic tube (average 29 days), and 33% needed a transurethral debris resection averaging 7 g. They were discharged within 23 hours. According to the short-term follow-up transrectal HIFU enables minimal invasive local prostate tissue ablation with high rates of negative biopsies, low PSA nadir, and low complication rate.

[Therapy of local prostatic carcinoma with high intensity focussed ultrasound (HIFU). Outcome and side-effects]. / Therapie des lokalen Prostatakarzinoms mit hoch intensivem fokussiertem Ultraschall (HIFU). Ergebnisse und Nebenwirkungen.

At the time of diagnosis, prostate cancer is organ confined in 70% of the cases. Of these patients, 25% undergo local therapy (surgery/radiation), and 75% risk disease progression by "watchful waiting" or systemic side effects through hormonal ablation. Local high-intensity focused ultrasound (HIFU) for minimal invasive tissue coagulation (85 degrees C) ablates prostatic tissue with high precision. Follow-up sextant biopsies (1.9) showed 80% of the patients to be cancer free. In those cases with residual cancer, the tumor mass was reduced by more than 90%. The PSA nadir in 97% was < 4 ng/ml, including 61% < 0.5 ng/ml. After primary HIFU, no severe side effects occurred (no fistula, no grade II/III incontinence, no rectal mucosa burn). As auxiliary treatments, all patients received a suprapubic tube (29 days), and 33% needed a transurethral debris resection (TUR 7 g). The patients were released from the hospital within 24 h after treatment. According to the short-term follow-up, transrectal HIFU enables minimal invasive local prostate tissue ablation with high rates of negative biopsies, low PSA nadir, and low complication rate.

Treatment of renal stones by extracorporeal shockwave lithotripsy: an update.

AIM: Despite the extensive experience with minimal invasive stone therapy, there are still different views on the ideal management of renal stones. MATERIALS AND METHODS: Analysis of the literature includes more than 14,000 patients. We have compared these data with long-term results of two major stone centers in Germany. The results have been compared concerning the anatomical kidney situation, stone size, stone localization and observation time. RESULTS: According to the importance of residual fragments following extracorporeal shock wave lithotripsy (ESWL), we have to distinguish between clinically insignificant residual fragments and clinically significant residual fragments (CIRF). 24 months following ESWL stone passage occurs as a continuous process, and if there are no clinical symptoms, any endoscopic procedure should be considered as overtreatment. According to these results, stone-free rates of patients increase in longer follow-up periods. Newer ESWL technology has increased the percentage of CIRF. CONCLUSION: We consider ESWL in most patients with renal calculi as first-line treatment, except in patients with renal calculi bigger than 30 mm in diameter.

High-intensity focused ultrasound in prostate cancer: results after 3 years.

BACKGROUND: Local high-intensity focused ultrasound (HIFU) is a minimally invasive method of coagulation (85 degrees C) that ablates prostatic tissue with high precision. PATIENTS AND METHODS: Over a 3-year period, 184 patients with organ-confined prostate cancer have undergone 232 sessions of transrectal HIFU therapy (mean duration 90 minutes) under spinal anesthesia at 2.25 or 3.0 MHz, 50 W, with a penetration depth of 25 mm. RESULTS: Follow-up sextant biopsies (mean 1.9) were cancer free in 80% of patients, and in patients with residual cancer, the tumor mass was reduced more than 90%. The nadir value of prostate specific antigen (PSA) was <4 ng/mL in 97%, including 61% who had values <0.5 ng/mL. After primary HIFU, no severe side effects (fistula, grade 2 or 3 incontinence, rectal mucosal burn) were seen. All patients had a suprapubic tube (mean 29 days), and 33% needed transurethral resection of debris (mean 7 g). Hospital discharge was within 23 hours after treatment. CONCLUSION: Transrectal HIFU enables minimally invasive local prostate tissue ablation with high rates of negative biopsies, low PSA nadir, and low complication rate. Further follow-up is needed to define the efficacy of disease control.

High-intensity focused ultrasound: complications and adverse events.

BACKGROUND: Transrectal high-intensity focused ultrasound (HIFU) is under investigation as a minimally invasive therapeutic option for elderly men with prostatic cancer. METHODS: From November 1996 to April 1999, 315 HIFU treatments with the Ablatherm (EDAP/TMS) were performed. A questionnaire including 50 theoretically possible adverse events was developed. Every patient complaint was recorded, including the physician's and patient's assessment, before and after therapy. Start date, end date, and period of every complaint were analyzed. RESULTS: As major adverse events after primary HIFU, there were six cases of stress incontinence grade 1. After repeat treatments with HIFU, rectourethral fistulas occurred in five patients, stress incontinence grade 1 in eight, and, after additive transurethral resection, grade 2 in one and grade 3 in two patients. Post-HIFU rectal mucosa burn decreased from 15% in 1996 to 0 within the last year. In all treatments, obstruction was avoided by suprapubic urinary diversion. Urinary tract infections (UTIs) were recorded initially in 58% of patients but later in only 8%. CONCLUSION: Transrectal HIFU proved to be a secure, minimally invasive therapeutic option for elderly men to avoid hormonal ablation or to postpone its first use.

High-intensive focused ultrasound in localized prostate cancer.

BACKGROUND AND PURPOSE: The results of the standard treatment for prostate cancer-radical prostatectomy-are not entirely satisfactory. A new local therapy, transrectal high-intensive focused ultrasound (HIFU), has been developed. We reviewed our experience with HIFU for palliation of localized prostate cancer. PATIENTS AND METHODS: Our series included 65 men with confirmed prostate cancer without detectable metastases who were not suitable candidates for radical prostatectomy. After prophylactic suprapubic cystostomy, the patients were treated using the Ablatherm version 2.32 under spinal anesthesia. The effects were monitored by serum prostate specific antigen assays, digital rectal examination, and biopsy. The mean follow-up is 10 months (range 1-18 months). RESULTS: There were no intraoperative or postoperative deaths, and there have been no deaths from prostate cancer. Residual cancer was detected in 35% of the patients in whom only biopsy-positive portions of the prostate were treated and 17% of those in whom the entire gland was treated. Retreatment was performed 1 month after the first session in these patients. The prostate volume increased an average of 30% after treatment, but by 3 months, the gland was 10% to 20% smaller than its original size. Three patients suffered complications secondary to overheating of the rectal wall or treatment too close to the external urethral sphincter. CONCLUSION: The low morbidity, minimal invasiveness, avoidance of systemic side effects, and potentially curative effect make HIFU a potentially useful option for the treatment of localized prostate cancer.

Current status of minimally invasive treatment options for localized prostate carcinoma.

INTRODUCTION: Prostate cancer is the leading malignancy in men today and an increase in detected localized prostate cancers is expected in the years to come. Even though radical prostatectomy is an effective treatment, it is associated with a considerable morbidity in some cases and efforts are made to provide minimally invasive alternative treatment options with equal efficacy but fewer side effects. METHODS: Cryosurgical ablation of the prostate (CSAP), brachytherapy, high-intensity focused ultrasound (HIFU) and radiofrequency interstitial tumor ablation (RITA) were evaluated after a literature review from a Medline Search (1966-1998). Furthermore, personal experience and latest data from the authors were taken into account. RESULTS: All alternative treatments nowadays make use of sophisticated technology, including the latest ultrasound devices for exact planning and monitoring of treatment, leading to increased safety compared to treatments in the 1960s and 1970s. Five-year results of CSAP show a PSA <1 ng/ml in 60% of cases whereas brachytherapy is able to achieve PSA <1 ng/ml in 80% of cases in a selected group. Recent outcome data come close to results of radical prostatectomy series. HIFU and RITA are promising new technologies that proved to be able to induce extensive necrosis, but the follow-up is too short to determine their definite places in the treatment of prostate cancer. CONCLUSION: Two alternative treatment options for localized prostate carcinoma, CSAP and brachytherapy, have been studied with a sufficient number of patients and an adequate follow-up. The overall results of brachytherapy are favorable when compared to CSAP and are in the same range as the outcome after radical prostatectomy. HIFU and RITA are relatively new techniques based on sophisticated technology that are very promising at present, but a longer follow-up is mandatory.

Transrectal high-intensity focused ultrasound using the Ablatherm device in the treatment of localized prostate carcinoma.

OBJECTIVES: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. The histologic effects and clinical outcome of the HIFU treatment were studied in two different groups of men with prostate carcinoma. METHODS: The HIFU treatment was performed under regional or general anesthesia with the Ablatherm device. In one group, HIFU was performed 7 to 12 days before radical prostatectomy, and meticulous histopathologic examination of the radical prostatectomy specimens was performed. The second group consisted of patients with localized prostate carcinoma for whom radical prostatectomy was not an option and who received HIFU treatment alone. RESULTS: In 14 patients treated with HIFU before radical prostatectomy, complete necrosis was seen in the treated region in all cases. On the dorsal border, however, incomplete destruction of tissue was noted, and in 4 cases a small vital tumor focus was seen. In the second group, of those patients in whom the entire prostate was treated, a negative biopsy result and a prostate-specific antigen (PSA) level less than 4 ng/mL was obtained in 60% and a PSA nadir less than 0.5 ng/mL in 55% of patients. CONCLUSIONS: HIFU treatment results in the two groups clearly demonstrate the potential of this modality in the treatment of localized prostate carcinoma. This study showed that extensive coagulative necrosis can be obtained in the treated areas; however, exact targeting is crucial and a prerequisite for extended clinical application of HIFU.

[Ureteral calculi. In situ ESWL treatment with booster technique]. / Harnleitersteine. ESWL-in-situ-Behandlung mit Boostertechnik.

After treatment of more than 3000 kidney and ureteral stones with the Siemens Lithostar Multiline the results of the first 1400 ureteral stone treatments using the "Booster technique" and 3-month follow-up findings are reported. There was a disintegration rate of 98% directly after treatment; 1 week after "Booster technique" treatment 96% of the patients were free of stones and without any symptoms. The 3-month follow-up showed a stone-free rate of 97%. Only in 13% of the cases auxiliary procedures were necessary, 7% of them before extracorporeal shock wave lithotripsy (ESWL) and 6% after ESWL. 43% of the treatments were performed without any premedication, anaesthesia or sedoanalgesia. Our data even prove that in situ ESWL is a safe and effective method for the treatment of ureteral stones. In comparison to endoscopic procedures, it is superior in regard to invasivity, side effects, complications and necessity of analgesia, while being just as efficient. Therefore it is recommended as first choice method in the treatment of ureteral stones.

Side effects of high-energy shockwaves in the human kidney: first experience with model comparing two shockwave sources.

The side effects of high-energy shockwaves (HESW) from two different sources on kidney parenchyma obtained from 10 patients treated by radical nephrectomy for renal cell carcinoma were examined. Immediately after nephrectomy, the kidneys were perfused with cold HTK solution and kept in hypothermia (8 degrees C) for a maximum of 4 hours. In five cases, the tumor-free parenchyma was treated at the upper or lower renal pole with 2000 shocks, energy output 21 kV, in an experimental electromagnetic shockwave system (Siemens Co., Erlangen). In the other five cases, the upper or lower poles were treated with 2000 shocks, energy output 24 kV, in an electrohydraulic spark gap system (MFL 5000; Dornier Medizintechnik, Germering). The resulting tissue defects were analyzed by histologic examinations. Changes after treatment with the electromagnetic system were found mainly in the tubules and midsized blood vessels in a well-defined focal area. Treatment with the electrohydraulic system was followed by tubular and glomerular lesions combined with vessel defects in a patchy pattern. The model is able to define the side effects of HESW in the human kidney and to test the side effects of different lithotripters.

First clinical experience and in situ treatment of ureteric stones using Lithostar Multiline lithotripter.

This article reviews the first experience using the Siemens Lithostar Multiline lithotripter in 372 consecutive treatments of ureteric and kidney stones. The disintegration rate was 97.7%, and a stone-free rate of 87% was achieved at the end of 3 months. Auxillary procedures were required in only 11% of the patients. No medication was required for pain management in 60.4% of the patients. The results were especially impressive in the management of ureteric stones, with a success rate of 91%, these patients being stone free after 1 week using the new booster technique. Analysis of the data indicates that the Siemens Lithostar Multiline is a safe, effective, and economically sound device to treat patients with ureteric and renal stones.

Localization of segmental arteries in renal surgery by Doppler sonography.

To avoid damage to major arteries of the renal parenchyma during nephrotomy, intraoperative Doppler sonography was used experimentally and clinical as an artery finder. In experiments with 7 beagles segmental arteries were detected easily and reliably by sonography, and the arterial course thus indicated correlated perfectly with arteriograms and casts. In a clinical trial the Doppler artery finder was used in 7 patients with staghorn calculi that were removed via the renal pelvis and additional multiple selective nephrotomies with as many as 7 selective nephrotomies in a single kidney there was no damage to the major arteries in any of these patients. Selective, avascular nephrotomy with the aid of the simple, quick and reliable technique of Doppler sonography promises improved functional results of transparenchymal stone manipulation.