980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate

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1 european urology 52 (2007) available at journal homepage: Benign Prostatic Obstruction 980-nm Diode Laser: A Novel Laser Technology for Vaporization of the Prostate Gunnar Wendt-Nordahl *, Stephanie Huckele, Patrick Honeck, Peter Alken, Thomas Knoll, Maurice Stephan Michel, Axel Häcker Department of Urology, University Hospital Mannheim, Mannheim, Germany Article info Article history: Accepted June 18, 2007 Published online ahead of print on June 26, 2007 Keywords: Benign prostatic enlargement Bleeding KTP laser Tissue ablation Transurethral resection of the prostate Abstract Objective: The wavelength 980 nm of a recently introduced diode laser system for treatment of benign prostatic enlargement offers a high simultaneous absorption in water and haemoglobin, and is postulated to combine high tissue ablative properties with a good haemostasis. Methods: The Ceralas HPD150 diode laser system was evaluated in the well-established ex vivo model of the isolated blood-perfused porcine kidney to evaluate tissue ablation capacity and haemostatic properties at different generator settings. A histological examination of the ablated renal tissue followed. The results were compared with the reference standards transurethral resection of the prostate (TURP) and potassiumtitanyl-phosphate (KTP) laser. Results: The diode laser displays a higher tissue ablation capacity, reaching g after 10 min, compared with the KTP laser ( g; p < 0.05), whereas only 30 s are needed to resect the tissue in the same surface area using TURP, resulting in g of tissue removal. With a bleeding rate of g/min, the diode laser offers haemostatic properties equivalent to the KTP laser ( g/min) and a significantly reduced bleeding compared with TURP ( g/min; p < 0.05). The corresponding depths of the coagulation zones are mm for the diode laser, mm for the KTP laser ( p < 0.05), and mm for TURP. Conclusions: In the standardised ex vivo investigation, the 980-nm diode laser offers a higher tissue ablation capacity and similar haemostasis compared with the KTP laser. In comparison with TURP, both tissue ablation and bleeding are significantly reduced. The promising ex vivo results warrant further clinical investigation. # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1 3, Mannheim, Germany. Tel ; Fax: address: gunnar.wendt-nordahl@uro.ma.uni-heidelberg.de (G. Wendt-Nordahl) /$ see back matter # 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 1724 european urology 52 (2007) Introduction Although transurethral resection of the prostate (TURP) is still considered the reference standard in surgical therapy of benign prostatic enlargement (BPE), it has been challenged by several alternative treatment modalities that try to match the efficacy of TURP but do reduce perioperative morbidity [1].In this context, several laser devices working on various wavelengths have been introduced in the last few decades [2,3]. The neodymium:yttrium-aluminum-garnet (Nd: YAG) laser (wavelength, 1064 nm) has a low absorption coefficient in tissue, and displays a deep penetration and a low energy density, resulting in coagulation necrosis without immediate ablative effects. In contrast, the holmium:yag (Ho:YAG) laser (wavelength, 2140 nm) is highly absorbed in prostatic tissue, and has a short penetration depth and a highenergy density. It heats the tissue above the boiling point and produces instant removal by vaporization. The physical properties of the lately introduced potassium-titanyl-phosphate laser (KTP laser), operating on a wavelength of 532 nm, offer an excellent haemostasis because the laser is highly absorbed by haemoglobin [4]. Its ablative properties are rather slow because the absorption in water is minimal, resulting in prolonged operation times [5,6]. A recently introduced diode laser system operates on a wavelength of 980 nm. Because this wavelength offers a high simultaneous absorption in water and haemoglobin, it is postulated to combine high tissue ablative properties with good haemostasis. In this study the diode laser was evaluated in an ex vivo model to determine its ablative and haemostatic properties systematically and to compare the results against TURP and KTP lasers as reference standard methods. 2. Methods 2.1. Equipment The Ceralas HPD150 (Biolitec-AG, Jena, Germany) is a diode laser system emitting a wavelength of 980 nm. The light is transmitted via a flexible 600-mm side-fire fibre to vaporize the tissue in a noncontact mode. The laser was evaluated at output power levels of 30, 50, 60, 80, 100, and 120 W in the continuous wave (cw) mode. Furthermore, the pulsed mode was tested with a fixed pulse length of 0.1 s and pause lengths of 0.01, 0.05, and 0.1 s at an output power of 100 W. TURP was performed with the use of a standard monopolar resectoscope (Karl Storz, Tuttlingen, Germany) activated by a high-frequency generator (Autocon II, Karl Storz) and set to an output power of 160 W, coagulation degree 2. Mannitol/sorbitol solution (Purisole SM, Fresenius, Bad Homburg, Germany) was used for irrigation. KTP laser ablation was performed with the use of the GreenLight PV laser generator (Laserscope, USA) and 600-mm side-fire fibres. An output power of 80 W was used in all experiments Ex vivo experiments The well-established model of the isolated blood-perfused porcine kidney was used to determine tissue ablation and haemostatic properties of the diode laser, the KTP laser, and TURP as previously described [7,8]. Porcine kidneys were removed immediately after slaughtering (Mannheim city slaughterhouse). After catheterisation of the renal artery and vein with a 10F catheter, the kidneys were perfused with 0.9% sodium chloride solution until the effluent was clear. Autologous blood was harvested and anticoagulized with sodium citrate. The kidneys and the blood were stored at 4 8C until the experiments started. The trials were performed in an acryl basin containing 0.9% sodium chloride solution at a temperature of 37 8C. All experiments were done by the same surgeon. Five experiments were performed per output power level and device; one kidney was used per experiment. Before commencing the experiments, each kidney was put in the basin for 30 min to adapt to the temperature. For the evaluation of tissue ablation, the catheters in the renal artery and vein were removed and the vessels were ligated. After removal of the capsule, the kidneys were weighed. Different output power levels were used to ablate the renal tissue in an area of 3 3 cm. The kidneys were weighed after 5, 10, and 15 min to determine the time-dependent amount of tissue ablation. Similarly, an area of 3 3 cm was resected with a drag speed of 1 cm/s to determine the amount of tissue removal by TURP. To evaluate the haemostatic properties of the devices, we perfused the kidneys with autologous blood by a roller pump via the catheter in the renal artery. The blood was drained from the kidney through the catheter in the renal vein to ensure a clear vision in the basin. The perfusion rate was set to 80 ml/min, resulting in a pressure of cm H 2 0. After removal of the renal capsule, a surface area of 9 cm 2 (3 3 cm) was ablated. The blood loss was quantified by the weight difference of a swab before and after it was placed on the bleeding surface for 60 s. The weight difference marked the amount of blood loss per minute. Afterwards, samples of the ablated renal tissue were taken and fixed in 4% formalin. After being embedded in paraffin at an interval of no longer than 2 wk after the experiments, the blocks were frozen at 19 8C, sectioned, and stained with haematoxylin-eosin. The depths of the coagulation zones induced by the lasers and TURP were determined under the microscope with the use of a calibrated calliper. Statistical data are presented as mean standard deviation. Statistical significance was evaluated with the use of the unpaired Student t test. A p value < 0.05 was considered to be statistically significant. 3. Results The ablation rates of the diode laser at different generator settings compared with the KTP laser and

3 european urology 52 (2007) Fig. 1 Ablation rate of the 980-nm diode laser at various output power levels compared with the potassium-titanylphosphate (KTP) laser and transurethral resection of the prostate (TURP). Use of high-power levels of tissue ablation has increased compared with KTP laser ( p < 0.05). Only 30 s are needed to resect the same surface area with TURP. N =5 experiments were carried out per parameter. TURP are displayed in Fig. 1. In the continuous wave (cw) mode, tissue ablation increased with increasing output power levels reaching g at 120 W after 15 min. With g of tissue removal, the KTP laser displayed a significantly lower ablation capacity than the diode laser in the same time interval ( p < 0.05). In comparison with TURP, both laser devices produced a significantly lower tissue removal. Using a drag speed of 1 cm/s with a pause of 2 s between the cuts, only 30 s were needed to resect the 3 3 cm surface area because the loop wire diameter was 0.5 cm (six cuts with 5 s per cut). The tissue removal achieved in the described fashion was g in 30 s. The bleeding rates were determined with the use of the same generator settings and are displayed in Fig. 2. Tissue ablation with the diode laser at 120 W resulted in a bleeding rate of g/min, which was not significantly different from the g/min rate of the KTP laser, whereas Fig. 2 Bleeding rate of the 980-nm diode laser at various output power levels compared with the potassium-titanylphosphate (KTP) laser and transurethral resection of the prostate (TURP) in a logarithmical scale. For both lasers, bleeding rate is reduced approximately by the factor 100 compared with TURP ( p < 0.05; n = 5).

4 1726 european urology 52 (2007) Fig. 3 Comparison of coagulation zone depth achieved with the 980-nm diode laser at different output power levels, potassium-titanyl-phosphate (KTP) laser, and transurethral resection of the prostate (TURP). The KTP laser displays a significantly higher coagulation depth than TURP and the diode laser ( p < 0.05; n = 5). TURP resulted in a significantly increased bleeding rate of g/min ( p < 0.05). Histological examination revealed that diode laser ablation resulted in a dense coagulation zone that increased with the output powers as displayed in Fig. 3. At 120 W, the coagulation zone depth was similar to that reached with TURP and significantly lower compared with the KTP laser. In addition to evaluation in the cw mode, experiments using the pulsed mode were also performed. The results are displayed in Table 1. Using the pulsed mode at a fixed pulse length of 0.1 s and varying pause lengths, we found that the ablation rate remained unchanged compared with the cw mode at 100 W. In contrast, bleeding increased in the pulsed mode with decreasing frequency. The sizes of coagulation zones were equal to those of the cw mode. 4. Discussion Although TURP is considered a reference standard in surgical therapy of BPE, it is associated with a certain morbidity, mainly caused by perioperative bleeding requiring transfusion or reintervention and irrigation fluid absorption (TUR syndrome) [9 11]. Therefore, a growing number of less invasive treatment modalities have been introduced in the last 2 decades, including several laser devices. The most widely used laser types comprise Nd:YAG, Ho:YAG, and KTP laser. The surgical techniques and treatment outcomes of these lasers are strongly dependent on the physical properties of the laser wavelengths. Because the wavelength of the Nd:YAG laser (1064 nm) displays a low absorption in prostatic tissue, it creates deep coagulation necrosis without any instant tissue removal displaying minimal blood loss. Treatment of BPE with the Nd:YAG laser is therefore characterised by long postoperative catheterisation times because the treatment success can take several weeks to set in. Furthermore, several studies have reported a low long-term durability of treatment success, leading to retreatment rates of over 20% after 2 yr [12,13]. In contrast to the Nd:YAG laser, the wavelength of the Ho:YAG laser (2140 nm) is highly absorbed in Table 1 Tissue ablation, bleeding rate, and coagulation depth of the diode laser at 100 W in the continuous wave (cw) and pulsed mode at a fixed pulse length of 0.1 s and varying pause lengths Parameter * cw mode Pulse pause 0.01 s Pulse pause 0.05 s Pulse pause 0.1 s Tissue ablation rate (g/10 min) Bleeding rate (g/min) Coagulation zone depth (mm) cw, continuous wave. * Bleeding increases with decreasing frequencies, while tissue ablation and coagulation zone depth are not altered. N = 5 experiments were carried out per parameter.

5 european urology 52 (2007) prostatic tissue, leading to instant vaporization without a considerable coagulation necrosis. Because simple ablative techniques proved to be rather time consuming, the use of the Ho:YAG laser for BPE treatment evolved to the more time-efficient techniques of holmium laser resection of the prostate (HoLRP) and holmium laser enucleation of the prostate (HoLEP). All described techniques display a low perioperative complication rate and produce durable results with low retreatment rates in the follow-up [14 17]. However, the learning curve for the more time-efficient techniques is rather steep, limiting the widespread use of these techniques. The wavelength of the widely used KTP laser (532 nm) offers above all a good haemostasis because it is strongly absorbed by haemoglobin. The laser energy is delivered via a side-fire fibre and produces instant vaporization of prostatic tissue. The technique is easy to learn, is associated with low perioperative morbidity, and produces results similar to those of TURP [6,18]. However, only limited long-term data are available, and treatment times are rather long because tissue vaporization is time consuming [4 6], limiting the patient collective to those with smaller glands. A diode laser working on a wavelength of 980 nm has been introduced lately to overcome the described problems of the established laser devices. Because this wavelength offers the highest simultaneous absorption in water and haemoglobin, it is postulated to combine high tissue ablation capacity and good haemostasis. Further advantages of the diode laser over KTP and Ho:YAG laser devices include a significantly lower energy consumption and the absence of a required high-voltage connexion, which improves mobility of the laser generator. In our ex vivo model we found tissue ablation to be easily feasible with the diode laser. The amount of removed tissue increased with longer treatment times and higher generator output power levels. We found the ablation capacity of the diode laser significantly higher compared with the KTP laser. Using the maximal output power of 120 W almost doubled the tissue removal reached with the KTP laser. Compared with TURP, the diode laser had significantly lower ablation capacity, which is, at least in part, due to limitations of our model (the cuts could be performed with a constant drag speed without the need to pause for coagulation). In vivo, the situation is different: Because a substantial amount of time is needed to coagulate bleeding vessels to minimize blood loss and increase intraoperative visibility in TURP, this procedure s advantage in time saving may be less pronounced. However, in clinical trials comparing Ho:YAG or KTP laser vaporization of the prostate with TURP, prolonged operation times were reported for the laser devices [6,15]. Our ex vivo results suggest that the 980-nm diode laser might overcome this problem because tissue ablation was almost twice as high as that reached with the KTP laser. The most appreciated advantage of KTP laser treatment is the almost bloodlessness of the procedure. Reich and colleagues [4] compared the KTP laser with TURP in a similar ex vivo model and found a significantly lower bleeding rate for the laser device. Our findings affirm their results and displayed a bleeding rate reduced by the factor 100 compared with TURP. Tissue ablation with the 980-nm diode laser resulted in bleeding similar to that of the KTP laser in the ex vivo model, indicating equal haemostatic properties. Clinical application of the diode laser has to show if these effects will be confirmed when used in vivo. Evaluation of the histological samples of ablated tissue revealed uniform and dense coagulation zones for the laser devices. Compared with the diode laser, TURP resulted in a coagulation zone of equal depth, but the coagulated tissue layer appeared less dense. The zone of coagulated tissue induced by the KTP laser was approximately twice as thick and appeared as equally dense as that of the diode laser. Our results for the diode laser suggest that a large amount of the energy is absorbed at the surface, resulting in vaporization of the tissue. In contrast, with the KTP laser, less energy is absorbed at the surface, resulting in deeper penetration and less vaporization of the tissue. This hypothesis explains the higher ablation capacity and lower coagulation zone depth of the diode laser. In addition to the described experiments using the diode laser in the cw mode, we performed further trials evaluating the performance when a pulsed mode was selected. Decreasing the frequency in the pulsed mode resulted in no change in the tissue ablation capacity, whereas bleeding increased with lower frequencies. According to these findings, we suggest using the laser in the cw mode in clinical application. Several studies prove laser vaporization of the prostate a safe and efficient method for BPE treatment [5,6,14,15,18]. However, a disadvantage of the technique is the rather low tissue ablation capacity of the established Ho:YAG and KTP laser devices, resulting in prolonged operation times. Our ex vivo findings suggest that the diode laser might have the potential to overcome this problem. In the ex vivo model, the diode laser showed a higher

6 1728 european urology 52 (2007) tissue ablation capacity and equal haemostatic properties compared with the KTP laser. Although the model we used provides a wellestablished tool for systematic evaluation of ablative devices, we are aware of the limitations of the study. All experiments were performed by using a blood-perfused porcine kidney in an ex vivo setting, which does not resemble human prostatic tissue in vivo in every aspect. Therefore, the results concerning ablative and haemostatic properties of the devices may be different when used in vivo. However, because the specific heat capacities in the renal and prostatic tissue are very similar, the blood-perfused kidney is a valuable model for studying laser procedures, in which the heat sink is of major importance [19]. Therefore, we believe our promising results warrant further clinical evaluation of the laser device to determine if its advantages found in the ex vivo setting offer a benefit in the in vivo setting. 5. Conclusions The 980-nm diode laser displays an increased tissue ablation capacity and equal haemostatic properties compared with the KTP laser in the ex vivo setting. In comparison with TURP, both tissue ablation and bleeding rates are significantly reduced. Our promising results warrant further clinical evaluation of the laser. Conflicts of interest The authors have nothing to disclose. Acknowledgements The authors thank Endrik Groenhoff from Biolitec AG for his technical support. References [1] Madersbacher S, Marberger M. Is transurethral resection of the prostate still justified? BJU Int 1999;83: [2] Fried NM. New laser treatment approaches for benign prostatic hyperplasia. Curr Urol Rep 2007;8: [3] Kuntz RM. Current role of lasers in the treatment of benign prostatic hyperplasia (BPH). Eur Urol 2006;49: [4] Reich O, Bachmann A, Schneede P, Zaak D, Sulser T, Hofstetter A. Experimental comparison of high power (80 W) potassium titanyl phosphate laser vaporization and transurethral resection of the prostate. J Urol 2004;171: [5] Sandhu JS, Ng C, Vanderbrink BA, Egan C, Kaplan SA, Te AE. High-power potassium-titanyl-phosphate photoselective laser vaporization of prostate for treatment of benign prostatic hyperplasia in men with large prostates. Urology 2004;64: [6] Bachmann A, Schürch L, Ruszat R, et al. Photoselective vaporization (PVP) versus transurethral resection of the prostate (TURP): a prospective bi-centre study of perioperative morbidity and early functional outcome. Eur Urol 2005;48: [7] Michel MS, Kohrmann KU, Weber A, Krautschick AW, Alken P. Rotoresect: new technique for resection of the prostate: experimental phase. J Endourol 1996;10: [8] Wendt-Nordahl G, Häcker A, Reich O, Djavan B, Alken P, Michel MS. The Vista system: a new bipolar resection device for endourological procedures: comparison with conventional resectoscope. Eur Urol 2004;46: [9] Mebust WK, Holtgrewe HL, Cockett AT, Peters PC. Transurethral prostatectomy: immediate and postoperative complications. Cooperative study of 13 participating institutions evaluating 3,885 patients. J Urol 1989;141: [10] Horninger W, Unterlechner H, Strasser H, Bartsch G. Transurethral prostatectomy: mortality and morbidity. Prostate 1996;28: [11] Rassweiler J, Teber D, Kuntz R, Hofmann R. Complications of transurethral resection of the prostate (TURP) incidence, management, and prevention. Eur Urol 2006;50: [12] Laguna MP, Alivizatos G, De La Rosette JJ. Interstitial laser coagulation treatment of benign prostatic hyperplasia: is it to be recommended? J Endourol 2003;17: [13] Muschter R. Free-beam and contact laser coagulation. J Endourol 2003;17: [14] Tan AH, Gilling PJ, Kennett KM, Fletcher H, Fraundorfer MR. Long-term results of high-power holmium laser vaporization (ablation) of the prostate. BJU Int 2003;92: [15] Mottet N, Anidjar M, Bourdon O, et al. Randomized comparison of transurethral electroresection and holmium: YAG laser vaporization for symptomatic benign prostatic hyperplasia. J Endourol 1999;13: [16] Gilling PJ, Kennett KM, Fraundorfer MR. Holmium laser enucleation of the prostate for glands larger than 100 g: an endourologic alternative to open prostatectomy. J Endourol 2000;14: [17] Wilson LC, Gilling PJ, Williams A, et al. A randomised trial comparing holmium laser enucleation versus transurethral resection in the treatment of prostates larger than 40 grams: results at 2 years. Eur Urol 2006;50: [18] Bouchier-Hayes DM, Anderson P, Van Appledorn S, Bugeja P, Costello AJ. KTP laser versus transurethral resection: early results of a randomized trial. J Endourol 2006;20: [19] Cooper TE, Trezek GJ. A probe technique for determining the thermal conductivity of tissue. J Heat Transfer 1972;94:133.