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Safety and Efficacy of Eraser Laser Enucleation of the Prostate: Preliminary Report
Safety and Efficacy of Eraser Laser Enucleation of the Prostate: Preliminary Report Lukas Lusuardi,*,† Andrew Myatt,† Manuela Sieberer, Stefan Jeschke, Reinhold Zimmermann and Günter Janetschek From the Department of Urology, Paracelsus Medical University Salzburg, Austria
Purpose: We ascertained the safety and efficacy of the 1,318 nm diode Eraser laser (Rolle and Rolle, Salzburg, Austria) for transurethral enucleation of the prostate. This laser has been successfully used to resect lung metastasis. It cuts and coagulates vascular rich tissue safely and effectively. We describe a prospective, randomized trial of Eraser laser prostate enucleation vs bipolar transurethral prostate resection. Materials and Methods: A total of 60 patients with lower urinary tract symptoms suggesting bladder outlet obstruction and a mean prostate size of 59.5 ml on transrectal ultrasound were randomized to Eraser laser prostate enucleation or bipolar transurethral prostate resection. Patients were assessed preoperatively, and 1 and 6 months postoperatively. Results: Eraser laser prostate enucleation was equivalent to bipolar transurethral prostate resection in improvement in International Prostate Symptom Score, maximal flow rate and quality of life. Laser enucleation was significantly superior to bipolar transurethral resection for measured blood loss (mean ⫾ SD 116.83 ⫾ 97.02 vs 409.83 ⫾ 148.61 ml), catheter time (mean 32.80 ⫾ 8.74 vs 65.73 ⫾ 13.72 hours) and hospital time (mean 45.13 ⫾ 14.77 vs 91.20 ⫾ 11.76 hours, each p ⬍0.05). Using the validated Clavien-Dindo system there were 3 grade Id and 1 grade II complications. Conclusions: Eraser laser prostate enucleation and bipolar transurethral prostate resection were equally safe and effective to relieve bladder outflow obstruction and lower urinary tract symptoms. This laser technique has the advantage of less blood loss, and shorter catheter time and hospital stay. Key Words: prostate, prostatic hyperplasia, laser therapy, transurethral resection of prostate, urinary bladder neck obstruction SURGICAL treatment for bladder outflow obstruction secondary to BPH is changing from conventional monopolar TURP to MISTs such as HoLEP or GreenLight™ LBO laser vaporization of the prostate.1 The clinical drivers of such a change include the decreased morbidity of these therapies compared to the morbidity associated with conventional TURP, such as perioperative bleeding, and prolonged catheteriza-
tion and hospital stay. HoLEP is also effective regardless of prostate size, an asset that conventional TURP does not have and for which retropubic prostatectomy is preferred.2– 4 The Eraser laser is a 1,318 nm diode laser that is effective for cutting, coagulating and sealing during resection for pulmonary metastasis.5,6 It creates 3 distinct tissue necrosis zones, including a central crater of
0022-5347/11/1865-1967/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 186, 1967-1971, November 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.07.026
AND
RESEARCH, INC.
Abbreviations and Acronyms BPH ⫽ benign prostatic hyperplasia ELEP ⫽ Eraser laser enucleation of prostate HoLEP ⫽ holmium laser enucleation of prostate I-PSS ⫽ International Prostate Symptom Score LBO ⫽ lithium borate MIST ⫽ minimally invasive surgical therapy PSA ⫽ prostate specific antigen PVR ⫽ post-void residual urine Qmax ⫽ maximum flow rate QOL ⫽ quality of life score TRUS ⫽ transrectal ultrasound TURP ⫽ transurethral resection of prostate Submitted for publication March 31, 2011. * Correspondence: Department of Urology and Andrology, Paracelsus Medical University Salzburg, Müllner Hauptstr. 48, 5020 Salzburg, Austria (telephone: ⫹43 662 4482 57439; FAX: ⫹43 662 4482 2971; e-mail: [email protected]). † Equal study contribution.
www.jurology.com
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SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
vaporized tissue, a broad and light zone of coagulation, and a third thin corona of hyperemia.7 This is unlike the 1,064 nm Nd:YAG laser, which creates a central zone of vaporization and a broad zone of interstitial bleeding.8 The effects of the Eraser laser were compared to those of the 120 W LBO in an isolated blood perfused porcine kidney model.9 There were statistically significant higher tissue ablation, higher output power efficiency, a lower bleeding rate and a deeper depth of tissue necrosis. The demonstrated properties of this laser potentially create the ideal device for efficiently and safely cutting prostate tissue. HoLEP uses a pulsed, end firing laser to enucleate the prostate adenoma. LBO is a side firing laser that ablates prostate tissue on contact. Since the Eraser laser is an end firing laser, prostate enucleation was thought to be possible. To our knowledge we present for the first time a series of patients with symptomatic bladder outflow obstruction treated with Eraser laser enucleation of the prostate, showing its safety and efficacy. Also, due to the expected good coagulation properties of this laser we studied blood loss in an accurate manner, as previously described.10–13 The low HemoCue® system is a measurement precise to ⫾ 5% that can be made at the bedside.10,12
MATERIALS AND METHODS From February 2010 to September 2010 we enrolled 60 patients with symptomatic bladder outflow obstruction. Patient evaluation included complete medical history, physical examination, digital rectal examination, urinalysis, urine culture, ultrasound of the upper urinary tract, PVR measurement, TRUS with prostate volume measurement, uroflowmetry, I-PSS, QOL, PSA, Hb and electrolytes. Patients were excluded from analysis if there was clinical suspicion of prostate cancer on digital rectal examination or increased PSA. In these patients TRUS guided biopsy of the prostate was done and they remained excluded from study. Patients were also excluded if they were on oral anticoagulation and 5␣-reductase inhibitors. All patients received low molecular weight heparin once daily, at hospitalization and subsequently until discharge home. All patients provided written, informed consent and the study was designed according to the principles of the Declaration of Helsinki. A total of 30 patients each were allocated to bipolar TURP and ELEP based on a balanced, blocked randomization schedule with a block size of 6 patients. Power calculation revealed a 10% difference in hospital stay or catheterization time using ␣ ⫽ 0.05 and  ⫽ 0.20, indicating that a sample size of 30 individuals per group was required. All data were analyzed using the Student t test for paired and unpaired data. Data are shown as the mean ⫾ SD. For all statistical comparison significance was considered at p ⬍0.05. The ELEP technique was designed to mimic HoLEP as exactingly as possible. All procedures were done by a
single surgeon (LL) who was experienced with HoLEP. We used a standard Storz laser resectoscope (Karl Storz®) with a 600 m end firing fiber. The laser was used at 120 W output power. In case of bleeding vessels the laser energy was defocused approximately 4 to 5 mm away from the surface. Standard tissue morcellation was performed using the Piranha® Laser Enuckleations-System. Tissue was sent for histological examination. Postoperatively irrigation was used as the standard overnight, as for bipolar TURP. The catheter was removed when urine was clear without irrigation. Bipolar TURP was performed by the same surgeon (LL) using the PlasmaKinetic™ system. Postoperative care was the same as that in patients who underwent ELEP. All patients were discharged home 24 hours after catheter removal. Blood loss during and after surgery was measured with the HemoCue low Hb photometer using the equation, Hb concentration in gm/l ⫻ irrigant volume in l/preoperative blood Hb concentration in gm/l.13 The HemoCue measurement was made during surgery by a certain method. After enucleation or resection had started the effluent was collected in a large bucket. At regular intervals the effluent was stirred until it was estimated that there was a homogenous solution. An aliquot was then passed through the HemoCue system. Irrigation speed was constant throughout each procedure, as was the height of the irrigation bag. For each procedure the amount of irrigation needed was different due to procedure duration. Thus, the mean HemoCue value was calculated. Bleeding velocity was determined as mean perioperative bleeding divided by resection or enucleation time. For ELEP morcellation time was not included but indicated separately.
RESULTS There were no statistically significant differences in baseline patient characteristics between the ELEP and bipolar TURP groups before surgery. Table 1 lists baseline characteristics. Mean operative time was statistically different between the 2 groups (table 2). TURP resection time was significantly longer than ELEP enucleation time (p ⬍0.05). In contrast, when morcellation time was added to enucleation time for ELEP, the procedure was significantly longer (p ⬍0.05). For each technique preoperative volume measured by TRUS and resected tissue weight were the same. No prostate cancer was found upon histological examination of morcellated or resected tissue. HemoCue blood loss was markedly decreased for ELEP compared to TURP (see figure). Table 2 shows that other parameters, such as Hb loss, blood loss per resected tissue and bleeding velocity, were lower in the ELEP group. Mean intraoperative mean irrigant volume was appreciably more for ELEP but
SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
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Table 1. Baseline characteristics of 2 groups
Age QOL I-PSS TRUS (ml) PSA Qmax (ml/sec) American Society of Anesthesiologists score Hb (gm/l) PVR (ml)
Mean ⫾ SD ELEP (range)
Mean ⫾ SD TURP (range)
p Value
66.5 ⫾ 5.96 (56–58) 5.1 ⫾ 1.04 (3–6) 26.9 ⫾ 5.34 (19–35) 59.5 ⫾ 15.13 (34–89) 3.5 ⫾ 1.22 (0.8–5.1) 6.8 ⫾ 2.43 (2–12) 2.7 ⫾ 0.69 (2–4) 15.0 ⫾ 0.97 (12.8–16.5) 176.5 ⫾ 75.39 (67–330)
65.7 ⫾ 6.2 (50–78) 4.9 ⫾ 1 (3–6) 25.4 ⫾ 4.8 (19–34) 59.1 ⫾ 14.2 (35–89) 3.9 ⫾ 1.8 (1.9–12) 6.4 ⫾ 2.2 (2–11) 2.7 ⫾ 0.7 (2–4) 14.8 ⫾ 1 (12.2–16.2) 180 ⫾ 78.7 (78–350)
0.63 0.32 0.27 0.91 0.39 0.54 0.85 0.55 0.86
catheterization and hospital times were less in the ELEP group. Table 3 lists followup data at baseline, and 1 and 6 months. There were significant improvements in Qmax, QOL and symptom scores in the 2 groups from baseline to each followup time point. There were no statistically significant differences between the ELEP and TURP groups throughout followup in symptom score or Qmax. Using the validated Clavien-Dindo system14 there were 3 grade Id complications and 1 grade II complication. In 2 patients in the TURP group and 1 in the ELEP group incontinence was treated conservatively with 1 pad daily (Clavien-Dindo Id). A symptomatic Escherichia coli urinary tract infection in the ELEP group was treated with oral antibiotics (ClavienDindo II). There were no blood transfusions or failed voiding trials. To date there has been no stricture or bladder neck contracture.
DISCUSSION As surgical treatment for symptomatic BPH, TURP and open prostatectomy remain the gold standards. Current widespread use of TURP shows that this procedure has stood the test of time. Open prostatectomy with adenoma removal from the capsule of
the prostate provides a high degree of disobstruction, symptomatic improvement and durability. However, these techniques are coupled with perioperative morbidity that may be unacceptable for a growing population of aging men with cardiovascular comorbidity.1 MIST techniques have shown promise to decrease perioperative morbidity and HoLEP also mimics adenoma removal in open prostatectomy.2– 4 HoLEP has not been widely adopted by the wider urological community due to a perceived steep learning curve, long operative time and the high cost of equipment despite level 1 evidence of its safety, efficacy, durability, short catheterization time and short hospital stay independent of prostate size.15 In this preliminary study we compared ELEP to TURP rather than to HoLEP since TURP is most commonly practiced by the worldwide urological community. Prostate enucleation was particularly used in this study because we believe that the current gold standard of MIST is HoLEP. Evidence for the durability of enucleation over vaporization techniques is most convincing. In a recent review data on HoLEP medium term and long-term functional results showed
Table 2. Perioperative data on 2 groups Mean ⫾ SD ELEP Operative time (mins) Enucleation/resection time (mins) Morcellation time (mins) Resected wt (gm) Retrieval rate (gm/min) Postop Hb (gm/dl) Blood loss (ml) Hb loss (gm/dl) Blood loss/resected tissue (ml/gm) Bleeding velocity (ml/min) Catheter time (hrs) Hospital time (hrs) Intraop irrigation vol (l)
69.00 ⫾ 10.23 46.70 ⫾ 6.55
Mean ⫾ SD TURP 60.43 ⫾ 60.43 ⫾
4.4 4.4
p Value ⬍0.05 ⬍0.05
21.93 ⫾ 6.53 32.20 ⫾ 9.36 0.44 ⫾ 0.07 14.72 ⫾ 0.97 116.83 ⫾ 97.02 0.24 ⫾ 0.16 6.07 ⫾ 3.87
— 32.17 ⫾ 8.74 0.43 ⫾ 0.08 13.22 ⫾ 0.75 409.83 ⫾ 148.61 0.61 ⫾ 0.71 10.91 ⫾ 3.38
— 0.989 0.674 ⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
2.90 ⫾ 1.41 32.80 ⫾ 8.74 45.13 ⫾ 14.77 21.17 ⫾ 2.84
5.49 ⫾ 0.75 65.73 ⫾ 13.72 91.20 ⫾ 11.76 14.07 ⫾ 1.60
⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
HemoCue blood loss estimation showed markedly decreased values for ELEP vs TURP. Squares represent mean. Horizontal bars represent 95% CI.
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SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
Table 3. Followup data on 2 groups
Baseline: ELEP TURP 1 Mo: ELEP TURP 6 Mos: ELEP TURP
Mean ⫾ SD Qmax (range)
Mean ⫾ SD I-PSS (range)
Mean ⫾ SD QOL (range)
Mean ⫾ SD PVR (range)
6.80 ⫾ 2.43 (2–12) 6.40 ⫾ 2.20 (2–11)
26.90 ⫾ 5.34 (19–35) 25.40 ⫾ 4.80 (19–34)
5.10 ⫾ 1.04 (3–6) 4.90 ⫾ 1.00 (3–6)
176.50 ⫾ 75.39 (67–330) 180.00 ⫾ 78.70 (78–350)
21.33 ⫾ 2.28 (16–25) 21.60 ⫾ 2.03 (16–25)
4.50 ⫾ 1.25 4.50 ⫾ 1.22
(2–7) (2–7)
1.37 ⫾ 0.49 (1–2) 1.37 ⫾ 0.49 (1–2)
35.97 ⫾ 8.86 (20–50) 36.37 ⫾ 9.46 (20–50)
21.57 ⫾ 1.94 (16–25) 21.60 ⫾ 1.57 (16–24)
4.20 ⫾ 1.06 4.43 ⫾ 1.17
(2–6) (2–6)
1.33 ⫾ 0.48 (1–2) 1.33 ⫾ 0.48 (1–2)
35.27 ⫾ 8.71 (20–50) 34.53 ⫾ 8.85 (20–50)
that it is durable with a mean Qmax of 21.9 ml per second and a mean 4.3% reoperation rate.15 These results were likely due to the complete enucleation achieved. A thulium:YAG laser was adopted for a vaporesection technique using the 70 W, 2,000 nm wavelength RevoLix® laser.16 This is a continuous wave laser, in contrast to the pulsed holmium laser. The Eraser laser is also a continuous wave laser. To date only 1 direct, controlled study has compared TURP with thulium laser resection of the prostate using the tangerine technique.17 Although the postoperative decrease in Hb was statistically significant for thulium:YAG compared to that for TURP, the thulium:YAG wavelength is in the range expected to cut rather than coagulate.7,17 Penetration depth of the 600 m, bare ended fiber, 100 W Eraser laser was measured in porcine kidney tissue as approximately 4.5 mm.9 In kidney tissue the hemostatic effects were better than those of the LBO laser.7,9 To our knowledge there is no animal study comparing the Eraser and thulium:YAG lasers but the 1,318 nm wavelength showed a good compromise of sufficient cutting and efficient coagulation.7 Penetration depth is important for laser BPH surgery. Dysuria and erectile dysfunction are adverse surgical outcomes of other laser techniques.8 Currently we are performing a study of the histological depth of tissue penetration of the Eraser laser in human prostate tissue. We are also comparing ELEP and thulium laser enucleation in a prospective, randomized trial with secondary outcome measures, including erectile dysfunction and dysuria. The holmium laser is a multipurpose urological device.18 The Eraser laser has no photothermal effects on urinary calculi but preliminary reports were recently published of its effectiveness for partial nephrectomy with no ischemia.7,9 We are currently performing animal and human studies to investigate the feasibility of Eraser laser assisted partial nephrectomy. Previous studies comparing enucleation techniques with standard TURP revealed proven bladder outlet obstruction on conventional urodynamics. In this study we did not perform conventional urodynamics
but included patients with lower urinary tract symptoms suggesting bladder outlet obstruction.19 While this could be a limitation of our series, this study is not a definitive comparison of the 2 techniques, merely a feasibility, safety and efficacy study. The hemostatic properties of the laser were assessed by a previously described method. Fagerström et al noted statistically significant less blood loss for bipolar than for monopolar TURP.13 In this preliminary study we compared ELEP to bipolar TURP rather than to HoLEP since TURP is most commonly practiced by the worldwide urological community and the bipolar method is currently our standard transurethral resection technique.19 No patient needed blood transfusion and overall estimated blood loss was small. Although postoperative Hb was significantly greater in the ELEP group, we are uncomfortable with using this as a scientific measure of blood loss. Postoperative Hb is affected by various confounding factors, such as preoperative Hb, patient hydration, intravenous fluid administration and comorbidity. The HemoCue system allows the study of other factors related to blood loss, such as blood loss per resected tissue and bleeding velocity.10–13 Bleeding velocity during ELEP is much less intense, a point that needs careful consideration. To calculate velocity we used the time needed to enucleate during ELEP vs the time needed for the entire TURP procedure, including cutting and coagulating the prostate using the bipolar technique. After enucleation was completed during ELEP the HemoCue evaluation was stopped since irrigation was clear, allowing good vision during morcellation. Also, during enucleation there was little need to constantly coagulate bleeding vessels. We observed that the properties of the laser permitted simultaneous cutting and coagulation of prostate tissue. Immediately postoperatively we were mindful that this study primarily concerned safety. To this end we routinely allowed continuous irrigation overnight in all patients. The decision to cease continuous irrigation depended on effluent color and was made by the nursing staff. Similarly the decisions to remove the catheter and discharge patients home were made with safety as our first concern. We think it is a significant finding that patients in the ELEP
SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
group had shorter indwelling catheter and hospital times. The surgeon who performed the surgery had prior extensive experience with HoLEP. Results clearly show efficacy and safety in accord with current HoLEP evidence. Eraser laser durability will be evaluated in further studies of a randomized, controlled trial in comparison with HoLEP. During HoLEP enucleation a fundamental principle is to develop the plane between the adenoma and the surgical capsule of the prostate. This action is achieved by cutting the tissue bridges with the holmium laser and also by considerable blunt dissection with the resectoscope beak. This is perceived as 1 of the more difficult aspects of the enucleation technique. Due to the deeper tissue penetration properties of the Eraser laser compared to the holmium laser there was some minor tissue charring but seemingly less bleeding. We do not believe that charring hampered recognition of the surgical capsule, making enucleation perfectly feasible. Also, after the correct plane is developed mainly blunt dissection is used together with division of the tissue
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bridges with the Eraser laser and control of bleeding points with defocused Eraser laser energy to truly mimic enucleation during HoLEP. The outstanding hemostatic properties of the Eraser laser are statistically superior to those of bipolar TURP. We believe that hemostasis could be superior to that of the holmium and thulium lasers. To this end catheter time and hospital time could be further decreased. We are currently performing randomized trials to compare ELEP to HoLEP and thulium laser enucleation.
CONCLUSIONS To our knowledge we present for the first time the ELEP technique using the 1,318 nm Eraser laser to treat symptomatic bladder outflow obstruction. Results show excellent safety and efficacy. Due to the hemostatic properties of the laser we believe that further studies are needed to evaluate whether this novel MIST could achieve durable functional results equivalent to those of HoLEP with superior hemostasis, and shorter catheter time and hospital stay.
REFERENCES 1. Ahyai SA, Gilling P, Kaplan SA et al: Metaanalysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic enlargement. Eur Urol 2010; 58: 384. 2. Kuntz RM, Ahyai S, Lehrich K et al: Transurethral holmium laser enucleation of the prostate versus transurethral electrocautery resection of the prostate: a randomized prospective trial in 200 patients. J Urol 2004; 172: 1012. 3. Montorsi F, Naspro R, Salonia A et al: Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2004; 172: 1926. 4. Tan AH, Gilling PJ, Kennett KM et al: A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003; 170: 1270. 5. Rolle A, Pereszlenyi A, Koch R et al: Laser resection technique and results of multiple lung metastasectomies using a new 1,318 nm Nd: YAG laser system. Lasers Surg Med 2006; 38: 26. 6. Rolle A, Pereszlenyi A, Koch R et al: Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser me-
tastasectomies with a new 1318-nm Nd: YAG laser. J Thorac Cardiovasc Surg 2006; 131: 1236.
benign prostatic hyperplasia of ⬎40 g. BJU Int 2006; 97: 85.
7. Khoder WY, Sroka R, Hennig G et al: The 1,318-nm diode laser supported partial nephrectomy in laparoscopic and open surgery: preliminary results of a prospective feasibility study. Lasers Med Sci 2011; 5: 120.
13. Fagerström T, Nyman CR, Hahn RG: Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique: a singlecentre randomized trial of 202 patients. BJU Int 2010; 105: 1560.
8. Breza J, Aboseif S, Zvara P et al: Transurethral Nd: YAG laser prostatectomy with a laterally firing fiber: local effects on tissue associated with erectile dysfunction. Lasers Surg Med 1995; 17: 364. 9. Wezel F, Wendt-Nordahl G, Huck N et al: New alternatives for laser vaporization of the prostate: experimental evaluation of a 980-, 1,318- and 1,470-nm diode laser device. World J Urol 2010; 28: 181. 10. Ekengren J and Hahn RG: Blood loss during transurethral resection of the prostate as measured by the HemoCue photometer. Scand J Urol Nephrol 1993; 27: 501. 11. Hahn RG, Fagerström T, Tammela TL et al: Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. BJU Int 2007; 99: 587. 12. Gupta N, Sivaramakrishna Kumar R et al: Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing
14. Clavien PA, Barkun J, de Oliveira ML et al: The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009; 250: 187. 15. Tan A, Liao C, Mo Z et al: Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction. Br J Surg 2007; 94: 1201. 16. Herrmann TR, Bach T and Imkamp F: Thulium laser enucleation of the prostate (ThuLEP): transurethral anatomical prostatectomy with laser support. Introduction of a novel technique for the treatment of benign prostatic obstruction. World J Urol 2010; 28: 45. 17. Xia SJ, Zhuo J and Sun XW: Thulium laser versus standard transurethral resection of the prostate: a randomized prospective trial. Eur Urol 2008; 53: 382. 18. Gravas S, Bachmann A and Reich O: Critical review of lasers in benign prostatic hyperplasia (BPH). BJU Int 2011; 107: 1030. 19. Engeler DS, Schwab C, Neyer M et al: Bipolar versus monopolar TURP: a prospective controlled study at two urology centers. Prostate Cancer Prostatic Dis 2010; 13: 285.
Purpose: We ascertained the safety and efficacy of the 1,318 nm diode Eraser laser (Rolle and Rolle, Salzburg, Austria) for transurethral enucleation of the prostate. This laser has been successfully used to resect lung metastasis. It cuts and coagulates vascular rich tissue safely and effectively. We describe a prospective, randomized trial of Eraser laser prostate enucleation vs bipolar transurethral prostate resection. Materials and Methods: A total of 60 patients with lower urinary tract symptoms suggesting bladder outlet obstruction and a mean prostate size of 59.5 ml on transrectal ultrasound were randomized to Eraser laser prostate enucleation or bipolar transurethral prostate resection. Patients were assessed preoperatively, and 1 and 6 months postoperatively. Results: Eraser laser prostate enucleation was equivalent to bipolar transurethral prostate resection in improvement in International Prostate Symptom Score, maximal flow rate and quality of life. Laser enucleation was significantly superior to bipolar transurethral resection for measured blood loss (mean ⫾ SD 116.83 ⫾ 97.02 vs 409.83 ⫾ 148.61 ml), catheter time (mean 32.80 ⫾ 8.74 vs 65.73 ⫾ 13.72 hours) and hospital time (mean 45.13 ⫾ 14.77 vs 91.20 ⫾ 11.76 hours, each p ⬍0.05). Using the validated Clavien-Dindo system there were 3 grade Id and 1 grade II complications. Conclusions: Eraser laser prostate enucleation and bipolar transurethral prostate resection were equally safe and effective to relieve bladder outflow obstruction and lower urinary tract symptoms. This laser technique has the advantage of less blood loss, and shorter catheter time and hospital stay. Key Words: prostate, prostatic hyperplasia, laser therapy, transurethral resection of prostate, urinary bladder neck obstruction SURGICAL treatment for bladder outflow obstruction secondary to BPH is changing from conventional monopolar TURP to MISTs such as HoLEP or GreenLight™ LBO laser vaporization of the prostate.1 The clinical drivers of such a change include the decreased morbidity of these therapies compared to the morbidity associated with conventional TURP, such as perioperative bleeding, and prolonged catheteriza-
tion and hospital stay. HoLEP is also effective regardless of prostate size, an asset that conventional TURP does not have and for which retropubic prostatectomy is preferred.2– 4 The Eraser laser is a 1,318 nm diode laser that is effective for cutting, coagulating and sealing during resection for pulmonary metastasis.5,6 It creates 3 distinct tissue necrosis zones, including a central crater of
0022-5347/11/1865-1967/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
Vol. 186, 1967-1971, November 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.07.026
AND
RESEARCH, INC.
Abbreviations and Acronyms BPH ⫽ benign prostatic hyperplasia ELEP ⫽ Eraser laser enucleation of prostate HoLEP ⫽ holmium laser enucleation of prostate I-PSS ⫽ International Prostate Symptom Score LBO ⫽ lithium borate MIST ⫽ minimally invasive surgical therapy PSA ⫽ prostate specific antigen PVR ⫽ post-void residual urine Qmax ⫽ maximum flow rate QOL ⫽ quality of life score TRUS ⫽ transrectal ultrasound TURP ⫽ transurethral resection of prostate Submitted for publication March 31, 2011. * Correspondence: Department of Urology and Andrology, Paracelsus Medical University Salzburg, Müllner Hauptstr. 48, 5020 Salzburg, Austria (telephone: ⫹43 662 4482 57439; FAX: ⫹43 662 4482 2971; e-mail: [email protected]). † Equal study contribution.
www.jurology.com
1967
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SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
vaporized tissue, a broad and light zone of coagulation, and a third thin corona of hyperemia.7 This is unlike the 1,064 nm Nd:YAG laser, which creates a central zone of vaporization and a broad zone of interstitial bleeding.8 The effects of the Eraser laser were compared to those of the 120 W LBO in an isolated blood perfused porcine kidney model.9 There were statistically significant higher tissue ablation, higher output power efficiency, a lower bleeding rate and a deeper depth of tissue necrosis. The demonstrated properties of this laser potentially create the ideal device for efficiently and safely cutting prostate tissue. HoLEP uses a pulsed, end firing laser to enucleate the prostate adenoma. LBO is a side firing laser that ablates prostate tissue on contact. Since the Eraser laser is an end firing laser, prostate enucleation was thought to be possible. To our knowledge we present for the first time a series of patients with symptomatic bladder outflow obstruction treated with Eraser laser enucleation of the prostate, showing its safety and efficacy. Also, due to the expected good coagulation properties of this laser we studied blood loss in an accurate manner, as previously described.10–13 The low HemoCue® system is a measurement precise to ⫾ 5% that can be made at the bedside.10,12
MATERIALS AND METHODS From February 2010 to September 2010 we enrolled 60 patients with symptomatic bladder outflow obstruction. Patient evaluation included complete medical history, physical examination, digital rectal examination, urinalysis, urine culture, ultrasound of the upper urinary tract, PVR measurement, TRUS with prostate volume measurement, uroflowmetry, I-PSS, QOL, PSA, Hb and electrolytes. Patients were excluded from analysis if there was clinical suspicion of prostate cancer on digital rectal examination or increased PSA. In these patients TRUS guided biopsy of the prostate was done and they remained excluded from study. Patients were also excluded if they were on oral anticoagulation and 5␣-reductase inhibitors. All patients received low molecular weight heparin once daily, at hospitalization and subsequently until discharge home. All patients provided written, informed consent and the study was designed according to the principles of the Declaration of Helsinki. A total of 30 patients each were allocated to bipolar TURP and ELEP based on a balanced, blocked randomization schedule with a block size of 6 patients. Power calculation revealed a 10% difference in hospital stay or catheterization time using ␣ ⫽ 0.05 and  ⫽ 0.20, indicating that a sample size of 30 individuals per group was required. All data were analyzed using the Student t test for paired and unpaired data. Data are shown as the mean ⫾ SD. For all statistical comparison significance was considered at p ⬍0.05. The ELEP technique was designed to mimic HoLEP as exactingly as possible. All procedures were done by a
single surgeon (LL) who was experienced with HoLEP. We used a standard Storz laser resectoscope (Karl Storz®) with a 600 m end firing fiber. The laser was used at 120 W output power. In case of bleeding vessels the laser energy was defocused approximately 4 to 5 mm away from the surface. Standard tissue morcellation was performed using the Piranha® Laser Enuckleations-System. Tissue was sent for histological examination. Postoperatively irrigation was used as the standard overnight, as for bipolar TURP. The catheter was removed when urine was clear without irrigation. Bipolar TURP was performed by the same surgeon (LL) using the PlasmaKinetic™ system. Postoperative care was the same as that in patients who underwent ELEP. All patients were discharged home 24 hours after catheter removal. Blood loss during and after surgery was measured with the HemoCue low Hb photometer using the equation, Hb concentration in gm/l ⫻ irrigant volume in l/preoperative blood Hb concentration in gm/l.13 The HemoCue measurement was made during surgery by a certain method. After enucleation or resection had started the effluent was collected in a large bucket. At regular intervals the effluent was stirred until it was estimated that there was a homogenous solution. An aliquot was then passed through the HemoCue system. Irrigation speed was constant throughout each procedure, as was the height of the irrigation bag. For each procedure the amount of irrigation needed was different due to procedure duration. Thus, the mean HemoCue value was calculated. Bleeding velocity was determined as mean perioperative bleeding divided by resection or enucleation time. For ELEP morcellation time was not included but indicated separately.
RESULTS There were no statistically significant differences in baseline patient characteristics between the ELEP and bipolar TURP groups before surgery. Table 1 lists baseline characteristics. Mean operative time was statistically different between the 2 groups (table 2). TURP resection time was significantly longer than ELEP enucleation time (p ⬍0.05). In contrast, when morcellation time was added to enucleation time for ELEP, the procedure was significantly longer (p ⬍0.05). For each technique preoperative volume measured by TRUS and resected tissue weight were the same. No prostate cancer was found upon histological examination of morcellated or resected tissue. HemoCue blood loss was markedly decreased for ELEP compared to TURP (see figure). Table 2 shows that other parameters, such as Hb loss, blood loss per resected tissue and bleeding velocity, were lower in the ELEP group. Mean intraoperative mean irrigant volume was appreciably more for ELEP but
SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
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Table 1. Baseline characteristics of 2 groups
Age QOL I-PSS TRUS (ml) PSA Qmax (ml/sec) American Society of Anesthesiologists score Hb (gm/l) PVR (ml)
Mean ⫾ SD ELEP (range)
Mean ⫾ SD TURP (range)
p Value
66.5 ⫾ 5.96 (56–58) 5.1 ⫾ 1.04 (3–6) 26.9 ⫾ 5.34 (19–35) 59.5 ⫾ 15.13 (34–89) 3.5 ⫾ 1.22 (0.8–5.1) 6.8 ⫾ 2.43 (2–12) 2.7 ⫾ 0.69 (2–4) 15.0 ⫾ 0.97 (12.8–16.5) 176.5 ⫾ 75.39 (67–330)
65.7 ⫾ 6.2 (50–78) 4.9 ⫾ 1 (3–6) 25.4 ⫾ 4.8 (19–34) 59.1 ⫾ 14.2 (35–89) 3.9 ⫾ 1.8 (1.9–12) 6.4 ⫾ 2.2 (2–11) 2.7 ⫾ 0.7 (2–4) 14.8 ⫾ 1 (12.2–16.2) 180 ⫾ 78.7 (78–350)
0.63 0.32 0.27 0.91 0.39 0.54 0.85 0.55 0.86
catheterization and hospital times were less in the ELEP group. Table 3 lists followup data at baseline, and 1 and 6 months. There were significant improvements in Qmax, QOL and symptom scores in the 2 groups from baseline to each followup time point. There were no statistically significant differences between the ELEP and TURP groups throughout followup in symptom score or Qmax. Using the validated Clavien-Dindo system14 there were 3 grade Id complications and 1 grade II complication. In 2 patients in the TURP group and 1 in the ELEP group incontinence was treated conservatively with 1 pad daily (Clavien-Dindo Id). A symptomatic Escherichia coli urinary tract infection in the ELEP group was treated with oral antibiotics (ClavienDindo II). There were no blood transfusions or failed voiding trials. To date there has been no stricture or bladder neck contracture.
DISCUSSION As surgical treatment for symptomatic BPH, TURP and open prostatectomy remain the gold standards. Current widespread use of TURP shows that this procedure has stood the test of time. Open prostatectomy with adenoma removal from the capsule of
the prostate provides a high degree of disobstruction, symptomatic improvement and durability. However, these techniques are coupled with perioperative morbidity that may be unacceptable for a growing population of aging men with cardiovascular comorbidity.1 MIST techniques have shown promise to decrease perioperative morbidity and HoLEP also mimics adenoma removal in open prostatectomy.2– 4 HoLEP has not been widely adopted by the wider urological community due to a perceived steep learning curve, long operative time and the high cost of equipment despite level 1 evidence of its safety, efficacy, durability, short catheterization time and short hospital stay independent of prostate size.15 In this preliminary study we compared ELEP to TURP rather than to HoLEP since TURP is most commonly practiced by the worldwide urological community. Prostate enucleation was particularly used in this study because we believe that the current gold standard of MIST is HoLEP. Evidence for the durability of enucleation over vaporization techniques is most convincing. In a recent review data on HoLEP medium term and long-term functional results showed
Table 2. Perioperative data on 2 groups Mean ⫾ SD ELEP Operative time (mins) Enucleation/resection time (mins) Morcellation time (mins) Resected wt (gm) Retrieval rate (gm/min) Postop Hb (gm/dl) Blood loss (ml) Hb loss (gm/dl) Blood loss/resected tissue (ml/gm) Bleeding velocity (ml/min) Catheter time (hrs) Hospital time (hrs) Intraop irrigation vol (l)
69.00 ⫾ 10.23 46.70 ⫾ 6.55
Mean ⫾ SD TURP 60.43 ⫾ 60.43 ⫾
4.4 4.4
p Value ⬍0.05 ⬍0.05
21.93 ⫾ 6.53 32.20 ⫾ 9.36 0.44 ⫾ 0.07 14.72 ⫾ 0.97 116.83 ⫾ 97.02 0.24 ⫾ 0.16 6.07 ⫾ 3.87
— 32.17 ⫾ 8.74 0.43 ⫾ 0.08 13.22 ⫾ 0.75 409.83 ⫾ 148.61 0.61 ⫾ 0.71 10.91 ⫾ 3.38
— 0.989 0.674 ⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
2.90 ⫾ 1.41 32.80 ⫾ 8.74 45.13 ⫾ 14.77 21.17 ⫾ 2.84
5.49 ⫾ 0.75 65.73 ⫾ 13.72 91.20 ⫾ 11.76 14.07 ⫾ 1.60
⬍0.05 ⬍0.05 ⬍0.05 ⬍0.05
HemoCue blood loss estimation showed markedly decreased values for ELEP vs TURP. Squares represent mean. Horizontal bars represent 95% CI.
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SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
Table 3. Followup data on 2 groups
Baseline: ELEP TURP 1 Mo: ELEP TURP 6 Mos: ELEP TURP
Mean ⫾ SD Qmax (range)
Mean ⫾ SD I-PSS (range)
Mean ⫾ SD QOL (range)
Mean ⫾ SD PVR (range)
6.80 ⫾ 2.43 (2–12) 6.40 ⫾ 2.20 (2–11)
26.90 ⫾ 5.34 (19–35) 25.40 ⫾ 4.80 (19–34)
5.10 ⫾ 1.04 (3–6) 4.90 ⫾ 1.00 (3–6)
176.50 ⫾ 75.39 (67–330) 180.00 ⫾ 78.70 (78–350)
21.33 ⫾ 2.28 (16–25) 21.60 ⫾ 2.03 (16–25)
4.50 ⫾ 1.25 4.50 ⫾ 1.22
(2–7) (2–7)
1.37 ⫾ 0.49 (1–2) 1.37 ⫾ 0.49 (1–2)
35.97 ⫾ 8.86 (20–50) 36.37 ⫾ 9.46 (20–50)
21.57 ⫾ 1.94 (16–25) 21.60 ⫾ 1.57 (16–24)
4.20 ⫾ 1.06 4.43 ⫾ 1.17
(2–6) (2–6)
1.33 ⫾ 0.48 (1–2) 1.33 ⫾ 0.48 (1–2)
35.27 ⫾ 8.71 (20–50) 34.53 ⫾ 8.85 (20–50)
that it is durable with a mean Qmax of 21.9 ml per second and a mean 4.3% reoperation rate.15 These results were likely due to the complete enucleation achieved. A thulium:YAG laser was adopted for a vaporesection technique using the 70 W, 2,000 nm wavelength RevoLix® laser.16 This is a continuous wave laser, in contrast to the pulsed holmium laser. The Eraser laser is also a continuous wave laser. To date only 1 direct, controlled study has compared TURP with thulium laser resection of the prostate using the tangerine technique.17 Although the postoperative decrease in Hb was statistically significant for thulium:YAG compared to that for TURP, the thulium:YAG wavelength is in the range expected to cut rather than coagulate.7,17 Penetration depth of the 600 m, bare ended fiber, 100 W Eraser laser was measured in porcine kidney tissue as approximately 4.5 mm.9 In kidney tissue the hemostatic effects were better than those of the LBO laser.7,9 To our knowledge there is no animal study comparing the Eraser and thulium:YAG lasers but the 1,318 nm wavelength showed a good compromise of sufficient cutting and efficient coagulation.7 Penetration depth is important for laser BPH surgery. Dysuria and erectile dysfunction are adverse surgical outcomes of other laser techniques.8 Currently we are performing a study of the histological depth of tissue penetration of the Eraser laser in human prostate tissue. We are also comparing ELEP and thulium laser enucleation in a prospective, randomized trial with secondary outcome measures, including erectile dysfunction and dysuria. The holmium laser is a multipurpose urological device.18 The Eraser laser has no photothermal effects on urinary calculi but preliminary reports were recently published of its effectiveness for partial nephrectomy with no ischemia.7,9 We are currently performing animal and human studies to investigate the feasibility of Eraser laser assisted partial nephrectomy. Previous studies comparing enucleation techniques with standard TURP revealed proven bladder outlet obstruction on conventional urodynamics. In this study we did not perform conventional urodynamics
but included patients with lower urinary tract symptoms suggesting bladder outlet obstruction.19 While this could be a limitation of our series, this study is not a definitive comparison of the 2 techniques, merely a feasibility, safety and efficacy study. The hemostatic properties of the laser were assessed by a previously described method. Fagerström et al noted statistically significant less blood loss for bipolar than for monopolar TURP.13 In this preliminary study we compared ELEP to bipolar TURP rather than to HoLEP since TURP is most commonly practiced by the worldwide urological community and the bipolar method is currently our standard transurethral resection technique.19 No patient needed blood transfusion and overall estimated blood loss was small. Although postoperative Hb was significantly greater in the ELEP group, we are uncomfortable with using this as a scientific measure of blood loss. Postoperative Hb is affected by various confounding factors, such as preoperative Hb, patient hydration, intravenous fluid administration and comorbidity. The HemoCue system allows the study of other factors related to blood loss, such as blood loss per resected tissue and bleeding velocity.10–13 Bleeding velocity during ELEP is much less intense, a point that needs careful consideration. To calculate velocity we used the time needed to enucleate during ELEP vs the time needed for the entire TURP procedure, including cutting and coagulating the prostate using the bipolar technique. After enucleation was completed during ELEP the HemoCue evaluation was stopped since irrigation was clear, allowing good vision during morcellation. Also, during enucleation there was little need to constantly coagulate bleeding vessels. We observed that the properties of the laser permitted simultaneous cutting and coagulation of prostate tissue. Immediately postoperatively we were mindful that this study primarily concerned safety. To this end we routinely allowed continuous irrigation overnight in all patients. The decision to cease continuous irrigation depended on effluent color and was made by the nursing staff. Similarly the decisions to remove the catheter and discharge patients home were made with safety as our first concern. We think it is a significant finding that patients in the ELEP
SAFETY AND EFFICACY OF ERASER LASER ENUCLEATION OF PROSTATE
group had shorter indwelling catheter and hospital times. The surgeon who performed the surgery had prior extensive experience with HoLEP. Results clearly show efficacy and safety in accord with current HoLEP evidence. Eraser laser durability will be evaluated in further studies of a randomized, controlled trial in comparison with HoLEP. During HoLEP enucleation a fundamental principle is to develop the plane between the adenoma and the surgical capsule of the prostate. This action is achieved by cutting the tissue bridges with the holmium laser and also by considerable blunt dissection with the resectoscope beak. This is perceived as 1 of the more difficult aspects of the enucleation technique. Due to the deeper tissue penetration properties of the Eraser laser compared to the holmium laser there was some minor tissue charring but seemingly less bleeding. We do not believe that charring hampered recognition of the surgical capsule, making enucleation perfectly feasible. Also, after the correct plane is developed mainly blunt dissection is used together with division of the tissue
1971
bridges with the Eraser laser and control of bleeding points with defocused Eraser laser energy to truly mimic enucleation during HoLEP. The outstanding hemostatic properties of the Eraser laser are statistically superior to those of bipolar TURP. We believe that hemostasis could be superior to that of the holmium and thulium lasers. To this end catheter time and hospital time could be further decreased. We are currently performing randomized trials to compare ELEP to HoLEP and thulium laser enucleation.
CONCLUSIONS To our knowledge we present for the first time the ELEP technique using the 1,318 nm Eraser laser to treat symptomatic bladder outflow obstruction. Results show excellent safety and efficacy. Due to the hemostatic properties of the laser we believe that further studies are needed to evaluate whether this novel MIST could achieve durable functional results equivalent to those of HoLEP with superior hemostasis, and shorter catheter time and hospital stay.
REFERENCES 1. Ahyai SA, Gilling P, Kaplan SA et al: Metaanalysis of functional outcomes and complications following transurethral procedures for lower urinary tract symptoms resulting from benign prostatic enlargement. Eur Urol 2010; 58: 384. 2. Kuntz RM, Ahyai S, Lehrich K et al: Transurethral holmium laser enucleation of the prostate versus transurethral electrocautery resection of the prostate: a randomized prospective trial in 200 patients. J Urol 2004; 172: 1012. 3. Montorsi F, Naspro R, Salonia A et al: Holmium laser enucleation versus transurethral resection of the prostate: results from a 2-center, prospective, randomized trial in patients with obstructive benign prostatic hyperplasia. J Urol 2004; 172: 1926. 4. Tan AH, Gilling PJ, Kennett KM et al: A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). J Urol 2003; 170: 1270. 5. Rolle A, Pereszlenyi A, Koch R et al: Laser resection technique and results of multiple lung metastasectomies using a new 1,318 nm Nd: YAG laser system. Lasers Surg Med 2006; 38: 26. 6. Rolle A, Pereszlenyi A, Koch R et al: Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser me-
tastasectomies with a new 1318-nm Nd: YAG laser. J Thorac Cardiovasc Surg 2006; 131: 1236.
benign prostatic hyperplasia of ⬎40 g. BJU Int 2006; 97: 85.
7. Khoder WY, Sroka R, Hennig G et al: The 1,318-nm diode laser supported partial nephrectomy in laparoscopic and open surgery: preliminary results of a prospective feasibility study. Lasers Med Sci 2011; 5: 120.
13. Fagerström T, Nyman CR, Hahn RG: Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique: a singlecentre randomized trial of 202 patients. BJU Int 2010; 105: 1560.
8. Breza J, Aboseif S, Zvara P et al: Transurethral Nd: YAG laser prostatectomy with a laterally firing fiber: local effects on tissue associated with erectile dysfunction. Lasers Surg Med 1995; 17: 364. 9. Wezel F, Wendt-Nordahl G, Huck N et al: New alternatives for laser vaporization of the prostate: experimental evaluation of a 980-, 1,318- and 1,470-nm diode laser device. World J Urol 2010; 28: 181. 10. Ekengren J and Hahn RG: Blood loss during transurethral resection of the prostate as measured by the HemoCue photometer. Scand J Urol Nephrol 1993; 27: 501. 11. Hahn RG, Fagerström T, Tammela TL et al: Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride. BJU Int 2007; 99: 587. 12. Gupta N, Sivaramakrishna Kumar R et al: Comparison of standard transurethral resection, transurethral vapour resection and holmium laser enucleation of the prostate for managing
14. Clavien PA, Barkun J, de Oliveira ML et al: The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009; 250: 187. 15. Tan A, Liao C, Mo Z et al: Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction. Br J Surg 2007; 94: 1201. 16. Herrmann TR, Bach T and Imkamp F: Thulium laser enucleation of the prostate (ThuLEP): transurethral anatomical prostatectomy with laser support. Introduction of a novel technique for the treatment of benign prostatic obstruction. World J Urol 2010; 28: 45. 17. Xia SJ, Zhuo J and Sun XW: Thulium laser versus standard transurethral resection of the prostate: a randomized prospective trial. Eur Urol 2008; 53: 382. 18. Gravas S, Bachmann A and Reich O: Critical review of lasers in benign prostatic hyperplasia (BPH). BJU Int 2011; 107: 1030. 19. Engeler DS, Schwab C, Neyer M et al: Bipolar versus monopolar TURP: a prospective controlled study at two urology centers. Prostate Cancer Prostatic Dis 2010; 13: 285.