Biomedical subjects

Maurice Stephan Michel

Publications and source records attributed to Maurice Stephan Michel.

At least 37 records · Page 2Linked to original sources

PubMed2004

Impact of holmium:YAG and neodymium:YAG lasers on the efficacy of DNA delivery in transitional cell carcinoma.

New approaches in the treatment of transitional cell carcinoma (TCC) are using gene therapy to influence the disease at the genetic level. Technical advances in genomics, the availability of tissue-specific gene promoters and other developments have made this approach more realistic. Transporting the gene into the target cell is still the major problem. Several transfection techniques have been introduced. Transfection of naked DNA is one of the simplest to perform but transfection rates have been very poor. We investigated the influence of laser energy on transfection efficacy in urothelial cancer cells in vitro with two types of medical lasers. A suspension of human transitional cancer cells (UM-UC3; 3.5 million cells/ml) was mixed with 200 microg of plasmid DNA (pEGFP-N1). Two types of laser energy, neodymium:YAG (Nd:YAG) and holmium:YAG (Ho:YAG), were applied to the cell suspension in different energy settings. Twenty four hours after treatment, transfection rates were measured with FACS analysis. Energy setting parameters that determine the efficacy of laser were investigated. The significance of different transfection rates was estimated with the student's t-test. We demonstrated that the Nd:YAG laser was not suitable for achieving significant transfection of the reporter gene to the cells. In contrast, the Ho:YAG laser produced satisfactory transfection rates. There was an increase in transfection with increasing frequency of laser pulses, from 16% with 2 Hz up to 40% with 10 Hz (p < 0.0005). Pulse frequency was therefore stabilised at 10 Hz. Pulse energy (mJ) showed the same dependency: a transfection rate of 18.3% was achieved with 1,000 mJ and 53.8% with 2,000 mJ (p > 0.0005). Additionally, we investigated the impact of total pulse number (imp) with different pulse energies. At 1,000 mJ, a transfection rate of 18.3% was estimated with 200 imp and 48.56% with 750 imp, (p < 0.0005). At 2,000 mJ, a transfection rate of 53.8% was achieved with 200 imp and 58.26% with 500 imp. The optimal laser setting observed in this experiment was 10 Hz, 2,000 mJ and 500 imp. This study indicates that the efficacy of naked DNA delivery into TCC in vitro is improvable by application of Ho:YAG laser energy. The Nd:YAG laser did not increase transfection rates in our model. Our results with the Ho:YAG laser are encouraging for further studies to optimise DNA delivery. As TCC tissue is relatively easy to access, this method could become an effective and minimally invasive procedure in urothelial cancer treatment.

Carcinoma, Transitional Cell↗

PubMed2004

The influence of oxalate on renal epithelial and interstitial cells.

Most renal stones in humans are composed of calcium oxalate. An increase in urinary oxalate levels has been shown to result in renal epithelial cell injury and crystal retention. However, the underlying mechanisms are unclear. Although the localization of primary stone formation and the associated cells playing the pivotal role in stone formation are still unknown, renal epithelial cells and interstitial cells seem to be involved in this process. The aim of this study was to evaluate the effects of oxalate on distinct renal epithelial and endothelial cells as well as fibroblasts. The first part focused on the toxicity of oxalate on the cells and a potential time- and dose-dependency. In the second part, renal epithelial cells were cultured in a two-compartment model to examine the vulnerability of the tubular or basolateral side to oxalate. LLCPK1, MDCK, renal fibroblast and endothelial cell lines were cultured under standard conditions. In part 1, cells were grown in standard culture flasks until confluent layers were achieved. Sodium oxalate was delivered at final concentrations of 1, 2 and 4 mM to either the apical or basolateral side (plain medium was delivered to the contralateral side). Cell survival was assessed microscopically by trypan blue staining after 1, 2 and 4 h. The influence of oxalate on proliferation and apoptosis induction was also investigated. In the second part, MDCK and LLCPK1 cells were grown in 6-well plates until confluent layers were achieved. Sodium oxalate at the above concentrations was applied, to either the apical or basolateral side and plain medium was delivered to the opposite side. The same protocol was then followed as in part 1. Part 1: sodium oxalate led to a time- and concentration-dependent decline in cell survival that was comparable in LLCPK1 and MDCK. Non-tubular cell lines like fibroblasts and endothelial cells were significantly more vulnerable to oxalate. These observations were reflected by significant impairment to cell proliferation. We could not demonstrate an induction of apoptosis in any cell line. Part 2: both cell lines were more vulnerable to oxalate on the basolateral side. This effect was more pronounced in MDCK cells at high oxalate concentrations (4 mM). Cells are apparently more resistant on the apical (tubular) side. Our results show that sodium oxalate has a negative effect on the growth and survival of renal epithelial cells and, to a greater extent, also fibroblasts and endothelial cells. We could not demonstrate any induction of apoptotic processes which implies a direct induction of cell necrosis. The finding of interstitial calcification and the proximity of tubules, vessels and interstitial cells make involvement of non-tubular renal cells in tissue calcification processes possible. Renal epithelial cells are apparently more vulnerable to oxalate on their basolateral side. Therefore, calcification processes within the interstitium may exert pronounced toxic effects to these cells, leading to inflammation and necrosis. These observations further support the idea of the interstitium as a site of primary stone formation.

Animals↗

PubMed2004

In vitro and ex vivo gene delivery into proximal tubular cells by means of laser energy--a potential approach for curing cystinuria?

Cystinuria is the cause of 1-2% of stones observed in adults and about 10% of those occurring in children. Recurrent stone formation and multiple operations cause considerable morbidity. We investigated the transfection efficiency of naked plasmid DNA in porcine kidney cells by applying holmium laser (Ho:YAG) energy in vitro as well as ex vivo in a porcine kidney papilla model. In the in vitro experiments, naked plasmid DNA was added to LLC-PK1 cells suspended in a medium and Ho:YAG laser applied with varying pulses. The transfection efficiency was measured by the expression of EGFP reporter gene in the cells by FACScan analysis and fluorescence microscopy. Ex vivo, papilla from porcine kidney was excised and naked plasmid DNA was added to the tissue in the medium. The laser was then applied and the cryosectioned tissue observed under fluorescence microscope. The efficiency of transfection in vitro significantly improved with the increase in impulses (P<0.01). Transfection at 50 impulses averaged 0.7+/-0.3%, at 200 impulses 28.3+/-7.7%, and at 500 impulses 36.1+/-3.1%. The cell mortality rate increased with higher pulse rate up to 70%. Ex vivo trials showed transfection in extended regions of the tissue and also in the peripheral layers of the papilla. Our study indicates that the transfection of benign kidney cells by Ho:YAG is a promising new gene transfer strategy. The ex vivo trials showed that peripheral renal tissue layers are susceptible to transfection by Ho:YAG applied from the papillary surface.

Cystinuria↗

PubMed2004

Micelle delivery of doxorubicin increases cytotoxicity to prostate carcinoma cells.

The use of doxorubicin as a chemotherapeutic agent is hindered by its toxic side effects on the normal cells of the body. The objective of this study was to determine if micelle-delivered doxorubicin could increase the effectiveness of doxorubicin against prostate carcinoma cells. Rat prostate carcinoma cells (MatLu) were cultured under standard conditions. Phosphate-buffered saline (PBS), doxorubicin and/or micelle solution (Pluronic 10500 solution) was added to the cell suspensions and incubated for 3 h. After incubation, cells were washed twice. Analysis consisted of: 1) immediate cell count and 2) proliferation assay at 24 and 144 h. After 24 h, samples with micelle-incorporated doxorubicin had 75% (10% pluronic with 10 microg/ml doxorubicin) and 80% (1% pluronic with 10 microg/ml doxorubicin) cell proliferation results compared with the control group. After 144-h incubation, these same two groups demonstrated cell proliferation results of only 30 and 43% of the control group. The in vitro cytotoxicity of doxorubicin against prostate carcinoma cells was dramatically increased by incorporating the molecule with polymeric micelles.

Analysis of Variance↗

PubMed2004

Expression of pro-angiogenic growth factors VEGF, EGF and bFGF and their topographical relation to neovascularisation in prostate cancer.

The aim of the study was to quantify the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in prostate cancer and adjacent non-tumorous tissue in a standardized experimental set-up and to evaluate the paracrine effects of three endothelial stimuli on neovascularisation. Immunohistochemical staining of prostate cancer (PCa) specimens for VEGF, bFGF, EGF and the endothelial marker CD31 was performed (n=56). Sections were analyzed for growth factor-positive cancer/epithelial cells as well as staining intensity in (I) malignant and (II) non-tumorous tissue. Within PCa the topographic relationship (TR) of maximum microvessel density (MWD) and maximum expression of each growth factor was assessed. The number of VEGF- and EGF-positive cells in PCa was significantly enhanced compared with non-tumorous tissue (p<0.0001), whereas there was no difference in staining intensity. In contrast, the staining intensity of bFGF sections revealed a stronger expression in non-tumorous tissue compared with PCa (p<0.0001). In benign glands, VEGF, EGF and bFGF expression is chiefly restricted to basal cells. VEGF and EGF displayed a close TR in 65 and 57% of cases, respectively, whereas bFGF revealed a close TR in only 43% of PCa specimens. The results outline the relationship of the investigated growth factors and angiogenesis in PCa, which is strongest for VEGF and EGF. The relevance of VEGF and EGF is underlined by the increased number of positive cancer cells. Although previously reported to be a pro-angiogenic growth hormone, bFGF appears to play an assimilably minor role in the angiogenesis of PCa.

Aged↗

PubMed2004

The Vista system: a new bipolar resection device for endourological procedures: comparison with conventional resectoscope.

OBJECTIVE: Conventional transurethral resection of the prostate (TURP) uses a monopolar electrocautery system in which the current passes from the active electrode through the patient's body towards the return plate and may cause distant negative effects. In this study a new developed resection device, the Vista system, using a bipolar electrocautery system and 0.9% sodium chloride solution for irrigation, was evaluated in an ex-vivo model. METHODS: The modified model of the isolated blood perfused kidney was used to determine cutting qualities, ablation rate, blood loss and coagulation depth of the bipolar resectoscope. After ablating the renal tissue of a perfused kidney in a surface area, blood loss was semiquantitatively determined. Afterwards samples were taken and processed for histological evaluation of the coagulation depth. We compared the new bipolar resection device against a conventional monopolar resectoscope. RESULTS: We found good cutting qualities of the bipolar resectoscope although it is more difficult to start a cut. The ablation rate is determined by the width of the electrode and is similar to the standard device (30 cm(2)/min). The bleeding is reduced with increasing output powers (26.13 +/- 6.15 g/min (level 5); 20.49 +/- 5,47 g/min (level 6); 13.16 +/- 5,47 g/min (level 7); 10.43 +/- 4.76 g/min (level 8) and lower compared to a conventional monopolar resectoscope (17.08 +/- 4.47 g/min). The coagulation depth increases with higher output powers but is reduced compared to the standard device (118 +/- 22 microm (level 5); 121 +/- 23 microm (level 6); 141 +/- 62 microm (level 7); 163 +/- 30 microm (level 8) versus 287 +/- 57 (monopolar resectoscope)). CONCLUSION: Our results with the bipolar resection device for TURP suggest that it may offer an alternative to conventional TURP. As active and the return electrode are placed on the resectoscope, high current densities are achieved locally and complications caused by distant negative effects of the current are theoretically reduced in vivo. Furthermore the risk of TUR syndrome is theoretically eliminated by using physiological sodium chloride solution for irrigation. To prove the clinical significance of our ex-vivo findings, clinical studies including large numbers of patients have to be performed.

Animals↗

PubMed2004

High-intensity focused ultrasound for ex vivo kidney tissue ablation: influence of generator power and pulse duration.

BACKGROUND AND PURPOSE: The therapeutic application of noninvasive tissue ablation by high-intensity focused ultrasound (HIFU) requires precise physical definition of the focal size and determination of control parameters. The objective of this study was to measure the extent of ex-vivo porcine kidney tissue ablation at variable generator parameters and to identify parameters to control lesion size. MATERIALS AND METHODS: The ultrasound waves generated by a cylindrical piezoceramic element (1.04 MHz) were focused at a depth of 100 mm using a parabolic reflector (diameter 100 mm). A needle hydrophone was used to measure the field distribution of the sound pressure. The morphology and extent of tissue necrosis were examined at generator powers of up to 400 W (P(el)) and single pulse durations of as long as 8 seconds. RESULTS: The two-dimensional field distribution resulted in an approximately ellipsoidal focus of 32 x 4 mm (-6 dB). A sharp demarcation between coagulation necrosis and intact tissue was observed. Lesion size was controlled by both the variation of generator power and the pulse duration. At a constant pulse duration of 2 seconds, a generator power of 100 W remained below the threshold doses for inducing a reproducible lesion. An increase in power to as high as 400 W induced lesions with average dimensions of as much as 11.2 x 3 mm. At constant total energy (generator power x pulse duration), lesion size increased at higher generator power. CONCLUSIONS: This ultrasound generator can induce defined and reproducible necrosis in ex-vivo kidney tissue. Lesion size can be controlled by adjusting the generator power and pulse duration. Generator power, in particular, turned out to be a suitable control parameter for obtaining a lesion of a defined size.

Animals↗

PubMed2004

Lymph and blood vessel architecture in benign and malignant prostatic tissue: lack of lymphangiogenesis in prostate carcinoma assessed with novel lymphatic marker lymphatic vessel endothelial hyaluronan receptor (LYVE-1).

PURPOSE: Due to the lack of specific markers the analysis of lymphatic vessel density (LVD) has been almost impossible in the past. We report the novel specific marker for lymphatic endothelium, lymphatic vessel endothelial hyaluronan receptor (LYVE-1), in prostatic, benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissue. Normal blood vessels were additionally quantified in BPH and PCa. MATERIALS AND METHODS: LYVE-1 lymphatics (LVD) and CD34 blood vessels were assessed in 20 paraffin sections of BPH and 50 of PCa tissue by immunohistochemistry in a standardized experimental setting. The regions of PCa, periphery of the tumor and nontumorous regions of the PCa specimens, and BPH tissue were evaluated. Double staining was done (LYVE-1/CD34). Acquired data were interrelated and compared to the pathological parameters of the specimens. RESULTS: Double staining revealed numerous CD34 blood vessels but only a few LYVE-1 lymphatic vessels in BPH and PCa sections. Mean LVD +/- SD was distinctly lower (0.55 +/- 0.93) in PCa tissue than in tumor periphery (2.45 +/- 1.93) and nontumorous (3.16 +/- 2.23) tissue (p <0.0001). Maximum LVD was observed in BPH (7.17 +/- 3.61), which differed markedly from nontumorous areas of PCa specimens (p <0.001). In contrast to LVD, significantly more blood vessels were found in PCa (116.00 +/- 39.25) than in BPH (60.30 +/- 19.34) tissue (p <0.001). CONCLUSIONS: LYVE-1 is a specific lymphatic endothelial marker in benign and malignant prostate tissues. It is a useful new marker for the investigation of lymphatics. To our knowledge we report the immunohistochemical visualization and quantification of lymphatic vessels in prostatic tissue for the first time. In contrast to the stimulated angiogenesis of blood vessels in PCa, the destruction of lymphatic vessels occurs rather than lymphangiogenesis.

Antigens, CD34↗

PubMed2003

Increase of AKT/PKB expression correlates with gleason pattern in human prostate cancer.

AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with tumor grade, and (c) whether AKT expression correlates with clinicopathological parameters. AKT expression was investigated by immunohistochemistry in sections from 56 paraffin-embedded prostate specimens displaying benign prostatic tissue (BPT), prostatic intraepithelial neoplasia (PIN), and primary tumors graded 2-5 according to Gleason. The staining intensity for AKT was significantly more pronounced in tumors compared to BPT, with PIN ranging between BPT and carcinomas. Similarly, the fraction of AKT-positive cells was higher in tumors than in BPT. A score of AKT expression (calculated as product from intensity and fraction of positive cells) ranging from 0-6 was also significantly higher in tumors than in BPT. Furthermore, the intensity of AKT expression in tumors showed a positive correlation with high preoperative serum levels of prostate specific antigen (PSA >/= 10 ng/ml, p = 0.0325). These data show that AKT is upregulated in prostate cancer and that expression is correlated with tumor progression.

Adult↗

PubMed2003

Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens?

The aim of this study was to correlate quantitative dynamic contrast-enhanced MRI (DCE MRI) parameters with microvessel density (MVD) in prostate carcinoma. Twenty-eight patients with biopsy-proven prostate carcinoma were examined by endorectal MRI including multiplanar T2- and T1-weighted spin-echo and dynamic T1-weighted turbo-FLASH MRI during and after intravenous Gd-DTPA administration. Microvessels were stained on surgical specimens using a CD31 monoclonal antibody. The MVD was quantified in hot spots by counting (MVC) and determining the area fraction by morphometry (MVAF). The DCE MRI data were analyzed using an open pharmacokinetic two-compartment model. In corresponding anatomic locations the time shift (Deltat) between the beginning of signal enhancement of cancer and adjacent normal prostatic tissue, the degree of contrast enhancement and the contrast exchange rate constant (k21) were calculated. The MVC and MVAF were elevated in carcinoma (p<0.001 and p=0.002, respectively) and correlated to k21 (r=0.62, p<0.001 and r=0.80, p<0.001, respectively). k21-values of carcinoma were significantly higher compared with normal peripheral but not central zone tissue. Deltat was longer in high compared with low-grade tumors (p=0.025). The DCE MRI can provide important information about individual MVD in prostate cancer, which may be helpful for guiding biopsy and assessing individual prognosis.

Aged↗

PubMed2003

Influence of acute selective endothelin-receptor-A blockade on renal hemodynamics in a rat model of chronic allograft rejection.

We have recently demonstrated up-regulation of renal endothelin (ET) synthesis in a rat model of chronic renal allograft rejection. Treatment with a selective ET-A receptor antagonist improved survival and reduced functional and morphological kidney damage. However, the underlying mechanisms have not yet been elucidated, as ET exhibits both hemodynamic and inflammatory properties. Therefore, in the present study we investigated acute hemodynamic effects of the selective ET-A receptor antagonist LU 302146 (LU) on chronic renal allograft rejection in rats. Experiments were performed in the Fisher-to-Lewis model of chronic renal allograft rejection. Lewis-to-Lewis isografts served as controls. After 2, 12, and 24 weeks, hemodynamic measurements were performed on anesthetized animals. Measurement of mean arterial pressure (MAP) was performed via a catheter in the femoral artery. Renal blood flow (RBF) was measured by an ultrasonic flow probe placed around the renal transplant artery. Medulla blood flow (MBF) and cortex blood flow (CBF) were determined with laser Doppler probes. Hemodynamic response upon intravenous bolus injection of LU (50 mg/kg) was investigated. The application of LU was followed by a decline in MAP that reached statistical significance only in isografts (ISOs) after 12 weeks and allografts (ALLOs) after 24 weeks. RBF slightly decreased in all groups; however, without reaching statistical significance. MBF showed a small increase in ALLO12 and ALLO24 whereas CBF slightly decreased in all groups. Acute ET-A receptor blockade does not induce important hemodynamic effects in kidneys undergoing chronic rejection. The lack of response to ET-A receptor blockade suggests that the beneficial effect of ET receptor antagonists in this model is likely to be due to improvement of renal morphology.

Animals↗

PubMed2003

Objective and subjective changes in patients with Peyronie's disease after management with shockwave therapy.

BACKGROUND AND PURPOSE: Very few reports have been published on the management of Peyronie's disease by shockwave therapy. Existing publications on this topic are based on subjective improvement described by the patients themselves. Our aim was to determine objectively the effect of shockwave therapy on the signs and symptoms caused by Peyronie's disease. PATIENTS AND METHODS: To date, 65 patients (age 58.4 +/- 8.7 years) have been enrolled in a therapeutic pilot study. The disease duration was 33.7 +/- 42.9 months. Inclusion criteria were palpable plaque together with deviation, pain (visual pain scale), or loss of distal rigidity. Clinical examination (prior to first therapy and 1, 6, and 18 months after last shockwave delivery) included palpation and sonography of the plaque (mean surface size 2.2 +/- 1.1 cm(2)), measurement of deviation, assessment of pain and distal loss of rigidity (artificial erection induced by intracavernosal injection of 5 microg of alprostadil [Caverject]). Shockwaves (1,000 impulses at 12 kV per square centimeter of plaque) were delivered to the nonerect penis once a week for a period of 5 weeks with the Minilith; Storz Medical. RESULTS: Eighteen months (N = 35) after the last shockwave session, the deviation angle had decreased from 59.3 degrees +/- 38.1 degrees to 49.3 degrees +/- 32.5 degrees (N = 24; P = 0.1496). Pain during erection disappeared in 15 of 17 patients and was reduced in 1 other patient (P < 0.0001). There was no effect on distal rigidity in any patient. Six patients achieved satisfactory sexual intercourse (vaginal penetration) before and 15 patients after shockwave therapy. The adverse effects were small skin hematomas in 90% of patients and initial transient macrohematuria in 30%. CONCLUSION: Our study demonstrates objective and subjective changes in patients with Peyronie's disease after shockwave therapy. Artificial erection served as a control to assess improvement of the deviation angle.

Humans↗

PubMed2003

Measurement of renal anatomy for prediction of lower-pole caliceal stone clearance: reproducibility of different parameters.

BACKGROUND AND PURPOSE: The architecture of the lower renal pole seems to have a considerable influence on caliceal stone clearance after different therapeutic modalities. The published data are partially inconsistent, and publications on reproducibility are completely lacking. The aim of this study was to evaluate the intraobserver and interobserver reproducibility of different measures of lower-calix anatomy. MATERIALS AND METHODS: We studied the intraobserver and interobserver reproducibility of parameters describing the lower-pole anatomy that are significant for treatment outcome. Forty renal units without urologic disease were analyzed by five independent urologists. Infundibular length (IL), infundibular width (IW), and lower infundibulopelvic angles (LIP) were measured by the Elbahnasy (LIP I), Keeley (LIP II), and Gupta (LIP III and LIP IV) methods. Statistical analysis of each parameter and investigator was performed. RESULTS: All LIP angles showed low interobserver correspondence: correlation coefficients (CC) did not exceed 0.44 (P < 0.05). Even the relatively clearly defined parameters IW and IL achieved CCs of only 0.63 and 0.49, respectively. The intraobserver correlation achieved better results: 0.73 (LIP I), 0.84 (LIP II), 0.73 (LIP III), 0.65 (LIP IV), 0.88 (IL), and 0.82 (IW). With the Elbahnasy method, almost all renal units were classified as favorable for stone persistence after shockwave lithotripsy. With the Keeley and Gupta methods, more than 50% of the kidneys were defined as having low clearance probability. CONCLUSIONS: Assessment of the chosen parameters is difficult and shows high interobserver variation. Inexperience in measuring the specific angles and low imaging quality can limit correct evaluation. The large number of kidneys with anatomy inappropriate for clearance of lower-pole stones may explain the poor outcome of shockwave treatment for stones in a lower calix. Prospective studies will determine the clinical value of anatomic assessments.

Humans↗

PubMed2003

Extracorporeal organotripsy for renal tumours.

PURPOSE OF THE REVIEW: The conviction that a renal cell carcinoma does not require the entire organ to be removed allows new therapeutic methods to be envisaged that involve only local tissue ablation, rather than the complete removal of the organ. The trend toward minimally invasive options in the management of renal tumours has prompted interest in energy-based ablation techniques as a possible alternative to radical or partial nephrectomy in selected patients. Cryoablation, radiofrequency interstitial tumour ablation, microwave thermotherapy and high-intensity focused ultrasound (HIFU) are among such techniques. HIFU has emerged as the least invasive of the possible tumour ablation methods. The present review addresses the current literature on experimental and clinical application of HIFU for extracorporeal organotripsy of renal tumours. RECENT FINDINGS: Clinical HIFU applications performed thus far in the treatment of renal tumours have only been experimental in nature. Specific case details were recently provided concerning a patient suffering from a multilocal renal cell carcinoma who underwent HIFU treatment with intent to cure, along with data from short-term (6 months) follow-up examinations. SUMMARY: HIFU is a promising but presently experimental procedure. It will achieve routine clinical application when technical problems concerning visualization of the target organ and lesion, precise control of lesion size, complete ablation of the tumour mass and reduction in side effects (skin burns) have been resolved. The objectives of further developments are to optimize ultrasound coupling and to provide on-line ablation evidence. At this time, HIFU should be reserved for selected patients in well designed clinical studies.

Carcinoma, Renal Cell↗

PubMed2002

Flexible ureterorenoscopy for the treatment of lower pole calyx stones: influence of different lithotripsy probes and stone extraction tools on scope deflection and irrigation flow.

The 7.5 and 9.0 F flexible ureterorenoscopes are used widely in endourology. These scopes, along with new available tools and probes, enable intrarenal ureteroscopic access to renal stones in the lower pole. Following individual clinical experiences the infundibulopelvic angle has to be respected for the selection of different scopes, tools and probes. The aim of this study was to determine the influence of different scopes, tools and probes on the angle of the active and passive flexion of the flexible ureterorenoscope. The angles of the active and passive flexion and maximum irrigation flow of different flexible ureterorenoscope (9.0 F Wolf, 7.5 F Olympus, 7.5 F Storz) were measured repeatedly in vitro using nine different inserted tools and/or probes. In addition, the maximum allowing for easy passage of the nine different tools/probes through the channel of the scope were measured. The Olympus scope without working instrument present, allows for the greatest deflection. The flexible Lithoclast, the non-nitinol baskets, and the 365 microns laser probes significantly inhibit the deflection of all scopes. The greatest deflection with inserted working tool was possible using the Wolf and Storz scopes. Both nitinol tools as well as the 200 microns laser probe had only minimal influence on the deflection. The 200 microns laser probe reduces the irrigation flow from 50 to 28 ml/min. In contrast, the baskets reduce the irrigation flow from 50 to 2 ml/min. There are significant differences of the active and passive flexion depending on the ureterorenoscopes itself and the different tools. In order to perform a successful flexible ureterorenoscopic stone treatment in the lower pole, the inhibition of the flexion of the different scopes together with the individual infundibulopelvic angle must be respected when selecting different tools and probes.

Alloys↗

PubMed2002

Comparative investigations on the retrieval capabilities of various baskets and graspers in four ex vivo models.

OBJECTIVES: The increasing application of ureterorenoscopy for the treatment of urolithiasis has produced a myriad of different help-tools for stone retrieval. In this study, we compared the retrieval capabilities of different baskets and graspers in ex vivo models and attempted to find the most appropriate tool for stone extraction considering the location and size of stone, number of stones and potential harm to urinary tract tissue. METHODS: We created four different ex vivo models with porcine kidneys and ureters and natural human stones: (1) single ureteral stone (4mm); (2) single impacted ureteral stone (6mm); (3) Steinstrasse; (4) single lower-pole stone (5mm). With the aid of four baskets of different design (flat-wire basket Segura and Nitinol basket Zerotip, helical Gemini, and Parachute) and three graspers (two-prong, three-prong Tricep, and Nitinol grasper Graspit) we performed repeated stone extraction 10 times in each model. The time for complete stone removal was calculated. Macroscopical evaluation of tissue damage was performed after each series. In the Steinstrasse model the frequency of instrument reinsertion into the ureter was also calculated. RESULTS: In the single ureteral stone model, the fastest stone removal was achieved with the two-prong graspers, three-prong graspers and helical basket (20, 26 and 31s, respectively). Segura and Parachute needed more time (55 and 86s, respectively). Impacted stones were removed fastest with the two- and three-prong graspers (38 and 52s, respectively), Segura and Gemini were slower (89 and 114s, respectively). The Steinstrasse was cleared fastest by the helical basket with the lowest frequency of endoscope reinsertion (66s, 1.4 reinsertion). The Segura, 149s with 3.2 reinsertion was needed for the same procedure. With the Parachute and two-prong graspers 163s, 1.8 reinsertion and 261s, 4.6 reinsertion were needed, respectively. During postprocedural macroscopical evaluation of uretral tissue, the Parachute basket and three-prong graspers demonstrated the highest risk of mucosal and muscle damage. In the lower-pole kidney model, the poor deflectability of the ureterorenoscope prevented access to the lower-pole with the two- and three-prong graspers. There was no significant difference in stone retrieval time between the remaining Nitinol basket Zerotip and Nitinol grasper Graspit (87 and 61s, respectively ). The number of failures was 4/10 for Zerotip and 5/10 for Graspit. No significant mucosal damage was noted with these tools. CONCLUSIONS: Our ex vivo models demonstrated that the design of graspers and baskets affects the time of stone retrieval in different situations and causes the various grades of tissue damage.

Animals↗

PubMed2002

Evaluation of superficial papillary ablation by endoscopic lasers in an ex vivo kidney model.

BACKGROUND AND PURPOSE: Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation. MATERIALS AND METHODS: Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program. RESULTS: Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J. CONCLUSIONS: Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.

Animals↗

PubMed2002

High intensity focused ultrasound as noninvasive therapy for multilocal renal cell carcinoma: case study and review of the literature.

PURPOSE: Noninvasive tumor ablation can be achieved by extracorporeally induced high intensity focused ultrasound. Clinical high intensity focused ultrasound performed to date for renal tumors have only been experimental in nature. We present specific details on a patient with renal cell carcinoma who underwent high intensity focused ultrasound with curative intent and long-term followup examinations. MATERIALS AND METHODS: Ultrasound waves were generated by a cylindrical piezoelectric element focused by a paraboloid reflector. High intensity focused ultrasound was applied to 3 tumors in 3 sessions with the patient under general anesthesia or sedation analgesia, followed by magnetic resonance imaging for 6 months. RESULTS: After treatment magnetic resonance imaging showed necrosis in the 2 tumors in the lower kidney pole within 17 and 48 days, respectively. The necrotic tumor area shrank thereafter within 6 months. The tumor in the upper pole was not affected by treatment due to absorption of the ultrasound energy by the interposed ribs. General anesthesia was required to apply high energy levels of focused ultrasound. Absorption of high intensity focused ultrasound in the tissue induced sharply demarcated thermonecrosis. For 50 years patients have been treated with high intensity focused ultrasound for different indications, focusing on the brain, eyes, prostate, liver and bladder. For the kidney experimental but only few clinical studies indicate sufficient tissue ablation. CONCLUSIONS: In our case contactless noninvasive application of high intensity focused ultrasound to 2 renal carcinomas achieved thermal ablation. When high intensity focused ultrasound energy was coupled correctly, no lesions occurred outside of the target area. Successful high intensity focused ultrasound application depended on optimum energy coupling, a sufficiently high ultrasound energy level and general anesthesia.

Carcinoma, Renal Cell↗