Transurethral Needle Ablation of the Prostate: A Minimally Invasive Treatment for Symptomatic Benign Prostatic Hyperplasia

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1 Symposium on Benign Prostatic Hyperplasia Transurethral Needle Ablation of the Prostate: A Minimally Invasive Treatment for Symptomatic Benign Prostatic Hyperplasia MARIO C. BEDUSCHI, M.D., AND JOSEPH E. OESTERLING, M.D. * needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland. Mayo Clin Proc 1998;73: Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of BPH = benign prostatic hyperplasia; RF = radio frequency; TURP =transurethral resection of the prostate T ransurethral resection of the prostate (TURP) is the major operation performed most often by American urologists, totaling several hundred thousand resections per year in the United States. Although an effective treatment for benign prostatic hyperplasia (BPH), TURP is by no means perfect. Approximately 20 to 25% of patients who undergo this operation do not have satisfactory long-term results, and reoperation rates after TURP have been reported to be as high as 10% during a follow-up period of 8 years. The morbidity rate ranges from 15 to 18%; intraoperative and postoperative blood loss necessitating blood transfusion, urethral or bladder neck strictures, erectile dysfunction, urinary incontinence, retrograde ejaculation, lower urinary tract infection, and epididymitis have been described. Furthermore, the mortality rate associated with TURP is approximately 0.2%, a number that may be even higher among men with major comorbidities. These untoward effects associated with TURP, the rising healthcare costs, and the increasing emphasis on avoidance of surgical treatment when possible have led clinical and investigational urologists to develop alternative medical and minimally invasive therapeutic options for symptomatic BPH. Today, TURP is no longer the only available nor always recommended approach for the management of symptomatic BPH. In this report, we review the rationale, technique, and clinical results with one of the minimally invasive therapies for BPH-transurethral needle ablation of the prostate. THE NEEDLE ABLATION SYSTEM General Principles The transurethral needle ablation system produces a state of thermotherapy (temperatures in excess of 45 C) and thermoablation (temperatures greater than 60 C) and treats symptomatic BPH by applying low-level radio-frequency (RF) energy to prostatic tissue. In its application for thermal tissue ablation, RF energy has distinctive properties. In the needle ablation procedure, the generated RF signal is delivered in the form of electrical energy to the target tissue (the prostate gland) by placement of two electrodes in contact with the patient. One of these elements, referred to as the active electrode (needle), has a small surface area and delivers the RF current into the target Fromthe Section of Urology (M.C.B. and, formerly, J.E.a.), University of Michigan Medical Center, Ann Arbor, Michigan. *Served on Board of Directors of VidaMed, Inc., from Sep. 27, 1995, until resignation on Aug. 26, 1996, and was granted stock options of the company's common stock in accordance with the company's director option plan. Address correspondence to Dr. M. C. Beduschi, Section of Urology, University of Michigan Medical Center, 1500 East Medical Center Drive, Ann Arbor, MI Mayo Clin Proc 1998;73: Mayo Foundationfor Medical Education and Research

2 Mayo Clin Proc, July 1998, Vol 73 tissue. Because the prostate cells resist the passage of the electrical current, thermal energy is generated by inductive heating of water molecules and friction; this process ultimately leads to tissue heating and ablation by coagulation necrosis. The unique nature of the RF signal dictates that it can be transmitted into tissue only through direct contact, and it has limited distance dissipation. Consequently, the thermal lesions occur only in the localized area of RF current flow (near the active electrode); their size is proportional to the amount of tissue in contact with the needle (exposed needle length) and the magnitude of the energy delivered. The second electrode, known as the "indifferent" electrode, is applied externally to the patient. It has a large surface area and functions by collecting RF current originating from the active electrode. At the site of the indifferent electrode, the RF current is not well concentrated and does not cause any tissue damage. Histopathologically, the thermal properties of needle ablation produce a coagulative necrotic lesion that involves both epithelial and stromal cells in the transition zone at a depth of 3 to 10 mm from the preserved urethra. The lesion of coagulation necrosis is circumscribed by a sharp, welldelineated peripheral zone of normal prostate. No nerve cells or axons are observed in the treated prostatic area, whereas nerve fibers abound in the untreated normal tissue; these fibers are predominantly located in the urethral mucosal layer, in the stroma surrounding the hyperplastic nodules, and beneath the prostatic capsule. Thus, in the ablated areas, all cells, irrespective of their origin, apparently are destroyed. Overall, transurethral needle ablation achieves temperatures in excess of 100 C in selected prostatic areas by using RF energy; the result is irreversible vascular damage and tissue necrosis after 3 to 5 minutes of exposure. Furthermore, the physical properties of the RF energy allow precise targeting of the tissue to be treated and preservation of adjacent organs and structures. The outcome is symptomatic efficacy and minimal associated morbidity. The Equipment The equipment used for transurethral needle ablation consists of three major components: (l) a rigid 22-F catheter, (2) a 0 optical lens, and (3) a low-level RF generator. Within the tip of the needle ablation catheter are two needles with their protective Teflon shield that can be deployed for an extension of up to 22 mm. After deployment, the two needles display at a 45 angle to each other and at a 90 angle to the catheter. Each needle and its covering shield advance and retract by controls on the catheter handle. Thermosensors are located at the tip of the shield to monitor the temperature of the prostatic tissue near the needle (treated area) and at the bullet head of the 697 catheter to monitor the prostatic urethral temperature. A knob located between the catheter and the handle allows rotation of the needles to either lateral lobe of the prostate. The specially designed needle ablation catheter has a centrallumen that facilitates passage of a 0 optical lens so that the needles can be precisely positioned in the prostate gland under direct vision. It is then connected tothe RF generator (a box with multiple digital displays for monitoring treatment variables), a light source, and an irrigation system. The generator is also connected to a rectal probe (for assessing the temperature of the anterior rectal wall) and a portable computer. It produces a 465-kHz RF signal that is transmitted through the catheter to each of the two needles. The digital panel displays the amount of energy being delivered, the treatment time, the temperature in the lesion being created, the rectal and urethral temperatures, and the tissue resistance or impedance at the needle sites. The system has a cutoff safety feature that is activated when the tissue impedance exceeds 400 ohms or when the urethral temperature surpasses 46 C. The former measure prevents tissue overheating or charring and thus avoids tissue selfinsulation and arrest of thermal propagation, whereas the latter feature protects the urothelium from thermal injury, which could cause patient discomfort. The Procedure The transurethral needle ablation procedure was designed to be performed as minimally invasive outpatient therapy, with patients being admitted and treated in the urologist's office. To undergo needle ablation of the prostate, the patient is taken to the procedure room and placed in the dorsal lithotomy position. After proper preparation and draping, 2% lidocaine jelly is injected intraurethrally at least 10 minutes before the procedure is begun. When necessary, local anesthesia can be supplemented with oral or intravenous sedation. General or spinal anesthesia is not usually required; patients are typically arousable and conversant during therapy. A broad-spectrum, prophylactic antibiotic is administered before the procedure. Under direct vision and with use of a 0 optical lens, the needle ablation catheter is advanced and positioned in the prostate gland. The length of the needle deployment within the prostate is calculated from the transverse measurement of the prostate made during previous transrectal ultrasonography. The depth of the needle deployment is determined by subtracting 6 mm from the distance between the urethra and the prostatic capsule. Pathologic studies have demonstrated that the thermal injury may extend 5 to 6 mm beyond the tip of the deployed needle; transversely, the lesions created during the ablation treatment may cover a distance of 10 mm. Concomitantly, the protective shields are deployed 5 to 6 mm over the shaft of the needle in order

3 698 Mayo Clin Proc, July 1998, Vol 73 treatment (a lesion in both the left and right sides of the prostate at the same level constitutes a plane) are created, beginning 1 em from the bladder neck and continuing at 1.5-cm increments until approximately 1 cm proximal to the verumontanum. At the conclusion of the procedure, the catheter is usually removed rather than left indwelling. The patient is dismissed home the same day, and an orally administered anti-inflammatory agent and antibiotic therapy are prescribed for several days. If the patient is unable to urinate before dismissal, he is instructed in clean intermittent catheterization and asked to perform it for 12 to 24 hours. INITIAL INVESTIGATIONS Fig. 1. Depiction of transurethral needle ablation system, showing needles positioned in prostatic parenchyma and producing a well-circumscribed thermolesion. to protect the urethra. This last feature is one of the major advantages of the needle ablation technique, inasmuch as it preserves the integrity of the urothelium and allows performance of the procedure with no or minimal discomfort to the patient. When both needles are appropriately positioned in the prostate gland, the RF energy is delivered with a power between 2 and 15 W for 5 minutes per lesion. The number of lesions created depends on the size of the prostate gland. One lesion (coagulation necrosis produced by the two needles) is usually performed per 20 g of prostate tissue (Fig. 1). Typically, one begins with a low-power setting in order to avoid desiccation of the tissue around the needle, which leads to a high impedance and the inability to propagate the RF energy. Therefore, the energy must be delivered continuously and slowly in order to achieve, after 4 minutes of treatment, a minimal temperature of 50 0 e at the thermocouple on the shield. The temperature at the end of the active needle tip is much higher (typically, wooe when the thermocouple on the shield indicates 50 C). This temperature differential has been demonstrated in several studies by using infrared thermal mapping. Separately for each needle, the RF generator automatically adapts the power that is required to achieve a minimal temperature of 50 0 e at the shield or wooe in the core of the lesions. These temperatures should be maintained for at least 1 minute so that the largest possible lesion is created. Depending on the size of the prostate gland (20 to 75 g), one to three planes of Transurethral needle ablation of the prostate makes use of RF energy to ablate specifically targeted tissue. The first clinical experience with use of this technology in humans was in the field of cardiology, when interstitial RF energy was used to treat patients with cardiac arrhythmias by destroying aberrant conductive pathway fibers responsible for this condition. After these initial encouraging results, Goldwasser and associates' investigated this form of thermotherapy as a potential treatment for symptomatic BPH. They speculated that the induction of irreversible thermal lesions in the prostatic tissue would decrease symptoms associated with bladder outlet obstruction and have fewer untoward side effects (such as retrograde ejaculation, erectile dysfunction, blood loss, or incontinence) than the more traditional therapies (for example, TURP). In their initial animal model study, the needle antennas from the needle ablation system were placed transurethrally into the prostatic tissue in 11 mongrel dogs. The RF generator was connected to the catheter and used to deliver the RF energy and create tissue ablation. Then the animals were sacrificed at various intervals after the interstitial RF treatment, and the specimens were recovered for examination. Pathologic evaluation revealed that the necrotic areas with small cavitations observed during the first few days after the procedure coalesced to form a large central cavity lined by normal transitional urothelium. These lesions were consistently found in the areas where the needles had been placed and were macroscopically characterized by being necrotic, conical, and 1 em in diameter. In addition, autopsy evaluations performed in one group of animals revealed no macroscopic or histologic signs of damage to the surrounding tissue (bladder and rectal wall). Aware of the limitations inherent in the canine model, specifically relative to the strikingly different glandularstroma ratio in comparison with the human prostate gland, these same investigators evaluated the transurethral needle ablation system in ex vivo human prostate glands.' Eight

4 Mayo Clin Proc, July 1998, Vol 73 prostate specimens obtained through suprapubic or transvesical prostatectomy were subsequently submitted to RF energy at a variety of power levels for various treatment durations. Substantial thermal lesions were elicited, with areas of coagulation necrosis measuring up to 15 mm by 30 mm being observed in the prostatic adenoma. These investigators determined that lesions were created whenever the tissue temperature exceeded 45 C; lesion size correlated with RF power delivery and the extent of needle penetration in the prostatic tissue. Thus, with this study, the efficacy and feasibility of the method in humans were first demonstrated by creating substantial thermal lesions in the prostatic tissue, and the ability to control lesion size indicated the safety of the procedure.' Addressing the issues of reproducibility and efficacy, Rasor and colleagues' evaluated the needle ablation technology in a turkey-breast model. The authors mapped the thermal gradients of the lesions produced by the needle ablation procedure through the use of an infrared imaging system and found that the central area of the lesion reached temperatures between 80 and 100 e. The authors concluded that the thermal destruction of prostatic tissue depends on the unique composition and thermoregulation properties of the target tissue. On the basis of their findings, a nomogram guide for setting the transurethral needle ablation device was developed, which allows anticipation of lesion size at various ablation times, power settings, and catheter-needle exposure extension. EARLY CLINICAL EXPERIENCE Encouraged by the excellent results with animal and ex vivo prostate models, Schulman and coworkers" at the University of Brussels conducted the first investigation of transurethral needle ablation of the prostate in humans. Their preliminary trial involved 25 men (prostate weight, 14 to 88 g) who underwent the needle ablation procedure before an open prostatectomy with recovery of the thermotreated prostate gland. Macroscopic examination of the surgical specimens obtained I day to 3 months after the needle ablation procedure revealed localized necrotic lesions with a sharp transition to untreated areas. These lesions had a mean size of 12 by 7 mm and 18 by 12 mm after 3 and 5 minutes of treatment, respectively. The urethra was spared with the use of the 90 catheter. Microscopic evaluation showed coagulative necrotic lesions with an extension of up to 30 by 15 mm. Specific immunohistochemical staining revealed destruction of all types of tissue components, glandular cells being slightly more thermoresistant than stromal tissue. Fifteen days after the needle ablation procedure, fibrosis could be observed in the surgical specimens. In agreement with other investigators, they found that the extension of the tissue necrosis is di- 699 rectly related to the power setting and the duration of needle exposure. '-3 Subsequently, this same group of investigators conducted an open-label clinical trial to evaluate transurethral needle ablation of the prostate in terms of efficacy, safety, and individual tolerance when performed as an outpatient procedure.' Fourteen patients with symptomatic BPH were enrolled in the trial; all study participants underwent assessment of urinary flow rate, postvoid residual volume, symptom score, and quality of life score at baseline and at 3 and 6 months after needle ablation. The mean peak urinary flow rate increased from 9.5 ± 3.3 mlis to 14.7 ± 6.3 mlis (P<0.05) at 3 months and to 15.0 ± 4.9 mlis at 6 months. The mean symptom score decreased from 21.9 ± 5.0 before the procedure to 10.2 ± 4.8 at 3-month follow-up (P<0.005), whereas the mean quality of life score improved from 4.4 ± 0.7 to 2.4 ± 1.2 after a 3-month period (P<O.005). Collectively, these early results in humans indicated that the needle ablation procedure produced an identifiable lesion in the prostate, improved the patient's ability to urinate, and could be performed on an outpatient basis. RECENT CLINICAL RESULTS Recently, data evolving from larger cohorts of patients treated with transurethral needle ablation of the prostate have become available. In 1996, Zlotta and colleagues" reported their results with the needle ablation technique applied to a cohort of 38 men who had acute urinary retention. Tolerance of the procedure was excellent (only topical anesthesia and intravenous sedation were needed). Thirty patients (79%) resumed voiding within a mean of 8.7 days (range, 2 to 27). At 6-month follow-up, the mean peak urinary flow rate was 10.4 ± 3.4 mlls, and the mean postvoid residual volume was 76 ± 45 ml. A total of six patients failed to resume voiding after the procedure; five of them underwent a simple retropubic prostatectomy, and one underwent TURP for management of the persistent condition. The treatment failures in this group were thought to be related to an insufficient number of treated areas (the mean weight of the prostate was 55.7 g). Nevertheless, this specific study clearly demonstrated that needle ablation is highly effective in relieving patients with urinary retention due to BPH and may be particularly suitable for such men with major associated comorbidities. Further investigations of transurethral needle ablation of the prostate were performed at various institutions worldwide, and the results have been presented at international meetings.":" The reported independent data unanimously concluded that the needle ablation procedure is safe and provides remarkable symptomatic improvement in most

5 700 men, although a considerable number of them had only modestly increased urinary flow rates. In a recent report, Schulman and Zlotta" presented their data on 150 patients with symptomatic BPH, who underwent follow-up for 2 years after transurethral needle ablation of the prostate. The following results were noted: the mean peak urinary flow rate increased from a baseline value of 9.8 mlls to 17.0 mlls at I-year follow-up (P<O.OI) and to 16.8 mlls at 2-year follow-up (P<O.OI). The mean American Urological Association symptom score improved from 21.0 to 8.8 at I-year follow-up (P<O.OOI) and to 9.2 at 2-year follow-up (P<O.OI). The mean postvoid residual urine volume decreased from 77 ml at baseline to 44 and 25 ml at I and 2 years, respectively (P<O.OI). In all patients, the needle ablation procedure was performed with use of either local anesthesia or local anesthesia and intravenous sedation. Most patients did not require catheterization, and the untoward effects were minimal. Thus, these investigators concluded that transurethral needle ablation of the prostate not only is an effective, minimally invasive treatment for BPH but also yields good, long-term (2-year) results. Although supportive of the needle ablation procedure, none of the investigations had a comparative control group-either a sham arm or a TURP arm-for accurate evaluation of the clinical efficacy and safety of the procedure. This latter issue was addressed by Oesterling and associates 14 in the North American clinical trial that compared transurethral needle ablation with TURP in the management of symptomatic BPH. Twelve medical centers across the United States participated in this investigation, in which 121 men 50 years of age or older and with symptomatic BPH persisting for at least 3 months were enrolled. Of the 121 men,65 (54%) were treated with needle ablation, and 56 (46%) underwent a classic TURP. The two cohorts were almost identical at baseline relative to the following factors: age, symptom score, bother score, peak urinary flow rate, and postvoid residual volume. Followup assessments performed at I, 6, and 12 months indicated that all variables improved significantly for both the needle ablation and TURP cohorts. With the exception of the variable quality of life, however, the authors noted that the results for TURP were slightly better at I-year follow-up. With reference to side effects in general, transurethral needle ablation was associated with fewer and less severe complications than was TURP. No man in the needle ablation-treated cohort had retrograde ejaculation, erectile dysfunction, or urinary incontinence. In addition, no patient who underwent needle ablation required a blood transfusion. Nevertheless, catheterization was necessary after the procedure in 40% of the patients who were treated with needle ablation and in all patients who underwent TURP. Mayo elin Proc, July 1998, Vol 73 For the needle ablation group, the catheter was removed routinely within 24 hours after the procedure. In contrast, the TURP-treated patients required a urethral catheter for 24 to 48 hours. This trial also obtained and examined data relating sexual function to these two treatment modalities. Specific information was gathered through the use of a questionnaire. For the needle ablation cohort of patients, no significant changes were noted, other than an increase in the ejaculate volume in some patients after the procedure. In contradistinction, more than 50% of the TURP-treated patients had a decrease in ejaculate volume, a side effect that is likely due to the occurrence of some degree of retrograde ejaculation. Patients treated with needle ablation had no significant variance in prostate size after the procedure, as determined by transrectal ultrasonography performed at 6- and 12month visits. This observation prompts questions about the mechanism by which needle ablation works and effectively decreases patient symptoms. The therapeutic response was initially thought to be due to the reduction in prostate volume after therapy. Currently, ever-growing evidence indicates that prostate volume is only marginally altered (if at all) after this type of thermotherapy; therefore, the decreased symptoms and the improved ability to urinate associated with needle ablation are not due to a reduction in size of the prostate or the elimination of obstructive tissue. The exact mechanism by which transurethral needle ablation achieves its therapeutic effect is unknown. In a recently published article, Zlotta and colleagues" evaluated 10 open prostatectomy specimens recovered I to 46 days after needle ablation treatment. Histologic sections were stained by two methods: hematoxylin-eosin and an immunohistochemical technique that uses enolase to mark neuronal tissue and antibodies directed against specific epithelial. and smooth muscle proteins. In the areas treated with needle ablation, both epithelial and stromal cells were destroyed in the transition zone at a depth of 0.3 to 1.0 em from the intact urethral epithelium. In addition, no staining ofaxons or isolated nerve cells was noted in the treated areas, whereas nerve fibers were routinely present in the control, untreated prostatic areas (submucosa and stroma). This severe thermal damage to intraprostatic nerve fibers may cause a long-term denervation of the a-receptors or sensory nerves (or both) in the prostate gland, causing an "a -blocker" type of response. FINANCIAL CONSIDERATIONS Any new or already existent modality for the treatment of BPH must not only satisfy classic therapeutic requirements such as safety, efficacy, and reproducibility but also be evaluated with regard to expense. Any alternative treat-

6 Mayo Clin Proc, July 1998, Vol ment option should also be compared financially with TURP, the "gold standard" treatment for BPH. The new minimally invasive treatment strategies must comply with the evolving changes in urology as well as be durable, have fewer side effects, and be cost-effective. Investigators are currently examining the financial aspects of needle ablation. The ability to perform the needle ablation procedure in the office with use of local anesthesia is likely to yield a cost advantage. REFERENCES 1. Goldwasser B, Ramon J, Engelberg 5, Ohad 0, Sharkey H, strul B, et al. Transurethral needle ablation (TUNA) of the prostate using low-level radiofrequency energy: an animal experimental study. Eur Urol 1993;24: Ramon J, Goldwasser B, shenfeld 0, Engelberg 5, Rasor Js, Edwards SO. Needle ablation using radiofrequency current as a treatment for benign prostatic hyperplasia: experimental results in ex vivo human prostate. Eur Urol 1993:24: Rasor Js, Zlotta AR, Edwards SO, Schulman CC. Transurethral needle ablation (TUNA): thermal gradient mapping and comparison of lesion size in a tissue model and in patients with benign prostatic hyperplasia. Eur Urol 1993;24: Schulman CC, Zlotta AR, Rasor Js, Hourriez L, Noel JC, Edwards SO. Transurethral needle ablation (TUNA): safety, feasibility, and tolerance of a new office procedure for treatment of benign prostatic hyperplasia. Eur Urol 1993;24: Schulman CC, Zlotta AR. Transurethral needle ablation of the prostate for treatment of benign prostatic hyperplasia: early clinical experience. Urology 1995;45: Zlotta AR, Peny MO, Matos C, Schulman CC. Transurethral needle ablation of the prostate: clinical experience in patients in urinary acute retention. Br J Urol 1996;77: Campo B, Bergamaschi F, Ordesi G, Corrada P, Oe Bastianl T. TUNA in BPH patients: urodynamic assessment at 18th month followup [abstract]. J Urol 1996;155(Suppl):403A 8. OesterlingJE, Issa MM, Roehrborn CG, Perez Marrero R, Bruskewltz R, Naslund MJ, et al, A single blind, prospective, randomized clinical trial comparing transurethral needle ablation (TUNATM) to transurethral resection of the prostate (TURP) for the treatment of benign prostatic hyperplasia (BPH)[abstract]. J Urol 1996;155(Suppl):403A 9. Lynch TH, Eardley I, Frick J, Goldwasser B, Ramon J, Wiklund P, et al. Transurethral needle ablation for the treatment of symptomatic benign prostatic hyperplasia [abstract]. JUral 1996;155(Suppl):709A 10. Minardi 0, Baldassari M, Caracenl E, Yehia M, Garofalo F, Crlstalll AF, et al. Trans-urethral needle ablation (T.U.N.A.) in benign prostatic hypertrophy [abstract]. Eur Urol 1996;30(Suppl 2): Pandit A, sriram R, Vlrdi J. Transurethral needle ablation (TUNA) of the prostate-one year followup [abstract]. Eur Urol 1996;30(Suppl 2): Glannakopoulos X, Grammeniatls E, Gartzlos A, Pappas G. Transurethral needle ablation (TUNA) of the prostate: preliminary results using the new generation TUNAIII catheter on patients with symptomatic BPH controlled by a series of 50 patients using the TUNA II device [abstract]. Eur Urol 1996;30(Suppl 2): Schulman CC, Zlotta AR. Transurethral needle ablation (TUNATM) of the prostate: clinical experience with two years follow-up in patients with benign prostatic hyperplasia (BPH). Eur Urol 1996;30(Suppl 2): Oesterling JE, Issa MM, Roehrborn CG, Bruskewitz R, Naslund MJ, Perez Marrero R, et al. Long-term results of a prospective, randomized clinical trial comparing TUNA to TURP for the treatment of symptomatic BPH[abstract]. J Urol 1997;157(Suppl): Zlotta AR, Raviv G, Peny MO, Noel JC, Haot J, Schulman CC. Possible mechanisms of action of transurethral needle ablation ofthe prostate on benign prostatic hyperplasia symptoms: a neurohistochemical study. J Urol 1997;157: End of Symposium on Benign Prostatic Hyperplasia, Part II. Part III will appear in the August issue.