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Pelvic Plexus Block is More Effective than Periprostatic Nerve Block for Pain Control During Office Transrectal Ultrasound Guided Prostate Biopsy: A Single Center, Prospective, Randomized, Double Arm Study
Oncology: Prostate/Testis/Penis/Urethra
Pelvic Plexus Block is More Effective than Periprostatic Nerve Block for Pain Control During Office Transrectal Ultrasound Guided Prostate Biopsy: A Single Center, Prospective, Randomized, Double Arm Study Francesco Cantiello,* Antonio Cicione, Riccardo Autorino, Carlo Cosentino, Francesco Amato and Rocco Damiano From the Urology Unit (FC, AC, RD) and School of Biomedical Engineering (CC, FA), Magna Græcia University of Catanzaro, Catanzaro, Italy, and Center for Laparoscopic and Robotic Surgery, Cleveland Clinic (RA), Cleveland, Ohio
Purpose: We compared intrarectal local anesthesia plus pelvic plexus block vs intrarectal local anesthesia plus periprostatic nerve block during transrectal ultrasound guided prostate biopsy. Materials and Methods: Patients were randomized 1:1 by a computer generated schedule into group 1—90 who received intrarectal local anesthesia (lidocaine 1.5%-nifedipine 0.3% cream) plus pelvic plexus block (2.5 ml lidocaine 1% plus naropine 0.75% injected on each side into the pelvic neurovascular plexus lateral to the seminal vesicle tip) and group 2—90 who received intrarectal local anesthesia plus periprostatic nerve block (2.5 ml of the same mixture injected on each side into the neurovascular bundles at the prostate-bladder-seminal vesicle angle) before transrectal ultrasound guided prostate biopsy. After the procedure patients were instructed to rate the level of pain/discomfort from 0 to 10 on the visual analog scale at certain time points, including during the introduction and presence of the probe in the rectum, during pelvic plexus block or periprostatic nerve block, during biopsy and 30 minutes after biopsy. Results: The 2 groups were similar in age, serum prostate specific antigen and total prostate volume. There was no difference in pain perception during probe introduction and pelvic plexus or periprostatic nerve block. Pain during prostate biopsy was significantly lower in group 1 than in group 2 (p ⬍0.001). The same trend was recorded for pain perception 30 minutes after biopsy (p ⫽ 0.001). There were no major complications. Conclusions: Pelvic plexus block under Doppler ultrasound guidance provides better analgesia than periprostatic nerve block during office based transrectal ultrasound guided prostate biopsy.
Abbreviations and Acronyms IRLA ⫽ intrarectal local anesthesia PNB ⫽ periprostatic nerve block PPB ⫽ pelvic plexus block PSA ⫽ prostate specific antigen TRUS ⫽ transrectal ultrasound VAS ⫽ visual analog scale Submitted for publication December 5, 2011. Study received institutional review board approval. * Correspondence: Urology Unit, Magna Græcia University of Catanzaro, Viale Europa, Germaneto, Catanzaro 88100, Italy (telephone: ⫹39 338 7914352; e-mail: [email protected]).
Key Words: prostate; biopsy; ultrasound, high-intensity focused, transrectal; pain; analgesia TRANSRECTAL ultrasound guided biopsy is the standard procedure for diagnosing prostate cancer. However, to date the most efficient biopsy scheme with the optimal number and location of cores has not yet been defined.1,2
Different forms of anesthesia have been used to make TRUS guided prostate biopsy a more comfortable procedure.3 PNB is simple, easy to perform, highly effective and widely considered the preferred method for pain control.4 –11
0022-5347/12/1882-0417/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.04.003 Vol. 188, 417-422, August 2012 RESEARCH, INC. Printed in U.S.A
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NERVE BLOCK FOR PAIN CONTROL DURING OFFICE PROSTATE BIOPSY
Prostate biopsy related pain has a dual origin, including the introduction and manipulation of the TRUS probe into anal canal and rectum, and needle passage through the prostate capsule.12 PNB alone cannot completely eliminate discomfort since it does not affect TRUS probe related pain. Thus, to optimize pain control additional IRLA before PNB was suggested.13–16 PPB is a more recently described method of local anesthesia and only 2 studies have been reported.17,18 In 1 study encouraging results were achieved with decreased pain during local anesthetic injection and prostate sampling compared to PNB.18 We report a prospective, randomized study comparing IRLA plus PPB vs IRLA plus PNB during TRUS guided prostate biopsy.
MATERIALS AND METHODS Study Design After receiving institutional review board approval this prospective, randomized, double arm trial was done at a tertiary care institution (Magna Græcia University, Catanzaro, Italy) between October 2010 and October 2011. Study inclusion criteria were PSA 4 ng/ml or greater, abnormal digital rectal examination and/or a TRUS suspicious lesion. Exclusion criteria were previous prostate biopsies, chronic prostatitis, chronic pelvic pain syndrome, inflammatory bowel disease, anorectal fissure/fistula, active urinary tract infection, bleeding disorder, and allergy to local anesthetic and myorelaxant agents. A total of 180 patients agreed to participate and provided informed consent. They were enrolled and randomized 1:1 by a computer generated schedule (see figure).
Treatment Allocation Patients were randomly assigned to 1 of 2 groups, including group 1—IRLA plus PPB and group 2—IRLA plus PNB before TRUS guided prostate biopsy. They were blinded to treatment group assignment.
Biopsy Procedure Anticoagulation or antiaggregant therapy was discontinued 7 days before biopsy. As antibiotic prophylaxis, oral
administration of levofloxacin 500 mg daily was administered starting the evening before the procedure until 4 days after the procedure. A cleaning enema was administered the evening before and the morning of biopsy. An SSD 5000 ultrasound scanner (Aloka, Wallingford, Connecticut) with a 7.5 MHz endorectal multiplanar end fire probe was used. The probe was rectilinear with a basal and middle part diameter of 16 mm and an apical diameter (corresponding transducer) of 18 mm. Before biopsy prostate volume was measured using the formula for an ellipse. As IRLA, in each group 10 ml lidocaine 1.5%-nifedipine 0.3% anesthetic-myorelaxant cream was applied around the anal ring, and in the anus and rectum 10 minutes before introducing the TRUS probe. Thereafter 22 gauge 20 cm spinal needle was used to inject 5 ml of a mixture of lidocaine 1% and naropine 0.75%. In group 1 with PPB 2.5 ml of the mixture were injected on each side into the pelvic neurovascular plexus lateral to the tip of the seminal vesicles under echo color Doppler guidance.17,18 In group 2 with PNB 2.5 ml of the mixture were injected on each side into the neurovascular bundles at the prostate-bladderseminal vesicle angle.4 –11 After 5 minutes prostate biopsies were performed with an automatic, spring loaded disposable biopsy gun and an 18 gauge Tru-Cut® needle by the same single operator using a 12-core scheme, including 6 parasagittal and 6 lateral cores covering the base, mid zone and apex bilaterally, with the patient in the lithotomy position. Additional cores were obtained from the area of suspected malignancy.
Pain and Complication Assessment All patients were hospitalized in our 1-day surgery center and observed for 2 hours after the procedure. They were discharged home only if they voided successfully. During the hospital stay patients were instructed by a resident blinded to the analgesia received to rate the level of pain/ discomfort from 0 to 10 on the VAS at certain time points, including during VAS 1—introduction and presence of the probe in the rectum, VAS 2—pelvic plexus block or periprostatic nerve block, VAS 3— biopsy procedure and VAS 4 —30 minutes after the procedure. Patients were also blinded to the local anesthetic injection site.
Consolidated Standard of Reporting Trials flow diagram of study participants
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The parameters recorded were biopsy related complications and the prostate cancer detection rate. Patients were given a nonvalidated self-administered questionnaire, which was completed at home in regard to complications and collected on day 14 after biopsy, when they returned for histological findings. Complications were graded as severe— hypotension or lipothymia/syncope requiring intravenous therapy, allergic reaction, hematuria and rectal bleeding requiring hospitalization, acute urinary retention and urosepsis with fever greater than 38.5C, and mild—self-limiting hematuria and/or rectal bleeding and hemospermia.
Statistical Analysis The primary end point was efficacy, as assessed by the VAS. A minimum 1-point difference in the 10-point VAS score is generally considered clinically significant when scores are assigned by patients.15 Based on a previous study comparing PPB and PNB sample size was calculated by assuming an SD of the VAS score at the prostate sampling step (VAS 3) equal to 1.95 in the PPB group and 2.16 in the PNB group,18 which yielded an average SD of 2.06. To detect a 1-point difference with 90% power and 2-sided 5% significance the study required a minimum of 180 patients randomized 1:1 in 2 arms. Differences in mean VAS scores were calculated using the Student t test with p ⬍0.05 considered statistically significant. All data were analyzed using Statistics Toolbox™.19 Analysis was done by intent to treat.
RESULTS The 2 groups were similar in age, serum PSA, total prostate volume and cancer detection rate (see table). Cancer was detected in 31 of 90 men (34.4%) with PPB and in 28 of 90 (31.1%) with PNB (Fisher exact test p ⫽ 0.75). Pain perception during probe insertion was similar in the 2 groups (p ⫽ 0.198). Similarly there was no difference in pain perception during PPB or PNB (p ⫽ 0.749). Pain during prostate biopsy was significantly lower in group 1 with PPB than in group 2 with PNB (p ⬍0.001). A significant difference was also noted for pain perception 30 minutes after biopsy (p ⫽ 0.001, see table). No side effects associated with local anesthesia and no modification of cardiovascular parameters
Patient characteristics and pain on VAS in groups 1 and 2 Mean ⫾ SD Group 1 Age PSA (ng/ml) Prostate vol (ml) VAS (time): 1 (probe insertion) 2 (PPB or PNB) 3 (biopsy) 4 (after 30 mins)
63.7 ⫾ 5.4 7.5 ⫾ 3.4 45.8 ⫾ 7.7 1.36 ⫾ 0.53 1.32 ⫾ 0.71 2.28 ⫾ 0.84 2.02 ⫾ 0.82
Mean ⫾ SD Group 2 63.2 ⫾ 5.5 8.5 ⫾ 4.5 47.5 ⫾ 10.9 1.22 ⫾ 1.34 ⫾ 3.37 ⫾ 2.41 ⫾
0.44 0.69 0.78 0.76
p Value (Student t test) 0.539 0.094 0.209 0.198 0.749 ⬍0.001 0.001
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were observed. There were no major complications. Two patients per group with prostatic hypertrophy were catheterized due to urinary retention after biopsy. In a group 1 patient there was fever greater than 38C, which was treated at home with intravenous antibiotics. There was no difference in PPB and PNB performance time.
DISCUSSION Prostate biopsy is associated with significant pain in approximately a fourth of patients20,21 and many who do not receive adequate anesthesia may refuse further TRUS biopsy, if needed.21,22 Pain during biopsy is mainly caused by the introduction and manipulation of the ultrasound probe in the anal canal and rectum, and needle penetration into the prostate capsule, which is richly innervated with autonomic sympathetic and parasympathetic fibers.4,23 Current evidence suggests that the PNB is safe, easy to perform and effectively decreases pain and discomfort in patients who undergo TRUS guided prostate biopsy.5–11 However, PNB does not completely eliminate pain since it cannot affect the discomfort related to TRUS probe manipulation, which may be more painful than biopsy.12 Thus, IRLA is required to decrease the pain associated with the TRUS probe in the first part of the biopsy procedure. The optimum would be a combination of IRLA plus PNB since the 2 components of the biopsy associated pain process, that is probe manipulation and prostate capsule puncturing, would be affected. Several studies have shown the superiority of combined anesthesia compared to PNB alone. Raber et al noted that PNB with perianal-intrarectal lidocaine-prilocaine cream compared to PNB alone significantly decreased pain during TRUS probe introduction and periprostatic anesthetic injection, although pain during biopsy was not decreased.14 Giannarini et al reported that the combination of PNB and perianal-intrarectal lidocaine-prilocaine cream was superior to PNB alone during all biopsy phases.15 Yun et al observed that additional instillation of intrarectal lidocaine gel before PNB provided effective higher analgesia than PNB alone but only during biopsy sampling while during PNB and 20 minutes after biopsy there was no statistically significant difference.24 They did not measure pain associated with TRUS probe introduction. Recently IRLA was achieved using myorelaxant cream to decrease anal sphincter tone and consequently the pain related to TRUS probe introduction. McCabe et al reported that PNB combined with perianal-intrarectal 0.2% glyceryl trinitrate paste compared to PNB with placebo significantly decreased the pain associated with TRUS guided biopsy, particularly during TRUS probe introduction.25
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In our previous study combined lidocaine-nifedipine cream topically placed with PNB was superior to PNB alone for decreasing pain and discomfort during TRUS probe introduction and PNB, and 30 minutes after biopsy.16 PPB was recently described as effective analgesia during TRUS guided prostate biopsy.17,18 The autonomic pelvic plexus consists of sympathetic and parasympathetic fibers. It is rectangular and 3 to 5 cm long, and its midpoint is at the tips of the seminal vesicles. It courses on either side of the rectum and is penetrated by numerous vessels going to and from the rectum, bladder, seminal vesicles and prostate. These vessels represent the lateral pedicles of the bladder and prostate, and cross sectioning them can damage the pelvic plexus, causing relative iatrogenic impotence. In fact, the pelvic plexus gives rise to the innervation of the prostate and cavernous nerves with the most caudal portion, that is the prostatic plexus.26,27 The prostatic plexus courses with the prostatic vascular strictures as the neurovascular bundle at the posterolateral border of the prostate. These posterolateral fibers are thought to be the main nerve supply of the prostate since only a few nerve fibers are situated on the superolateral and anterior surfaces of the prostate.18,23,26,28 PPB was first described by Wu et al.17 They injected 5 ml 1% lidocaine lateral to the tip of the seminal vesicles under grayscale ultrasound guidance. This procedure did not decrease biopsy associated pain. Later more promising results were reported by Akpinar et al.18 In a single center, prospective, randomized study they compared the efficacy of PNB with that of PPB (2 ml 2% lidocaine on each side). They noted a significantly lower VAS pain score in the PPB group during local anesthetic injection (3.12 vs 2.05, p ⫽ 0.0007) and prostate sampling (4.97 vs 2.7, p ⬍0.001). The reason for the different findings in the study by Wu et al17 and that by Akpinar et al18 may relate to the smaller, higher concentration of local anesthesia in the latter with a briefer injection time and by the use of Doppler ultrasound with more precise localization of the pelvic plexus. We performed IRLA with a lidocaine 1.5%-nifedipine 0.3% cream and achieved a low VAS pain score during TRUS probe introduction in each group. This cream is a mixture of a topical, short acting anesthesia and a myorelaxant agent, designed to provide 12-hour palliation of the symptoms of anal rhagades. This leads to better pain control during TRUS probe introduction due to the anesthetic and myorelaxant effects, and to longer lasting palliation of discomfort due to the pharmacokinetics of the drug and its duration of action. VAS 2 pain scores for PPB or PNB were similar to those reported in the literature for groups 1 and
2.15,16,18,24 Also, patients who received PPB experienced less pain than those who received PNB during prostate sampling and 30 minutes after biopsy. PPB may provide better anesthesia because its action is proximal to the prostate with a block of more nerve fibers. In fact, PPB affects all sensory nerve fibers of the prostatic plexus, including fibers that enter the prostatic capsule at the base, superolateral and anterior surfaces. However, the VAS 3 (biopsy) result was higher than in the current literature. This may have been due to the small amount of local anesthesia (2.5 ml of a mixture of lidocaine 1% and naropine 0.75% on each side). We used a small amount of local anesthesia injected several cm away from 2 points (tip of the seminal vesicle and the prostate-bladder-seminal vesicle angle) to avoid spreading anesthesia along the nerve fibers, which seemed likely for this higher anesthetic volume. We do not think that VAS 3 pain scores were influenced by the time between anesthetic injection and biopsy (5 minutes). We used a mixture of lidocaine 1% and naropine 0.75%, that is a short and a long acting anesthesia, to avoid the rebound pain effect. Lee-Elliot et al addressed the rebound pain effect using lidocaine alone.29 In a randomized trial comparing lidocaine vs lidocaine and a long acting anesthetic periprostatic injection the combination significantly attenuated the 1-hour rebound pain noted after the short acting anesthesia alone. Our study was not powered to perform such subanalysis. Thus, specific assessment with patient stratification based on age was not done. However, similar to that reported by others,15,24 we perceived that older patients and those with a smaller prostate seemed to have lower VAS pain scores. Doppler ultrasound allows precise delivery of local anesthesia to the pelvic plexus area, avoiding violation of the vascular structures and contributing to the low rate of complications, particularly vascular complications, associated with this technique without causing longer application time.18 The higher cost of combined analgesia and Doppler ultrasound is a serious concern, given the exponentially growing number of procedures performed worldwide. This economic limitation must be weighed against the superior pain control of IRLA plus PPB compared to that of IRLA plus PNB or a single analgesia. Cost-effectiveness analysis is strongly advocated to specifically address this issue. Placebo, no intervention and IRLA alone arms were not included in this study, given the strong evidence that combined anesthesia decreases the pain associated with biopsy.14,16 Further studies are needed to determine whether PPB results in more adhesions, which would make
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the surgical steps more difficult, and whether it interferes with normal recovery of erectile function and urinary continence after surgery. Finally, a VAS is often used in epidemiological and clinical studies, and its strengths and weaknesses are well evaluated.30 Although a VAS is far
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from being an accurate scientific and reproducible tool, to our knowledge there is currently no better way to compare the anesthetic effect during prostate biopsy. In conclusion, PPB under Doppler ultrasound guidance provides better analgesia than PNB during office based TRUS guided prostate biopsy.
REFERENCES 1. Heidenreich A, Bellmunt J, Bolla M et al: EAU guidelines on prostate cancer. Part 1: screening, diagnosis and treatment of clinically localized disease. Eur Urol 2011; 59: 61.
11. Kaver I, Mabjeesh NJ and Matzkin H: Randomized prospective study of periprostatic local anesthesia during transrectal ultrasound-guided prostate biopsy. Urology 2002; 59: 405.
2. Scattoni V, Raber M, Capitanio U et al: The optimal rebiopsy prostati scheme depends on patient clinical characteristics: results of a recursive partitioning analysis based on a 24-core systematic scheme. Eur Urol 2011; 60: 834.
12. Luscombe CJ and Cooke PW: Pain during prostate biopsy. Lancet 2004; 363: 1840.
3. Autorino R, De Sio M, Di Lorenzo G et al: How to decrease pain during transrectal ultrasound guided prostate biopsy: a look at the literature. J Urol 2005; 174: 2091. 4. Nash PA, Bruce JE, Indudhara R et al: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 1996; 155: 607. 5. Soloway MS and Obek C: Periprostatic local anesthesia before ultrasound guided biopsy. J Urol 2000; 163: 172. 6. Lynn NN, Collins GN, Brown SC et al: Periprostatic nerve block gives better analgesia for prostatic biopsy. BJU Int 2002; 90: 424. 7. Leibovici D, Zisman A, Siegel YI et al: Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study. J Urol 2002; 167: 563. 8. Berger AP, Frauscher F, Halpern EJ et al: Periprostatic administration of local anesthesia during transrectal ultrasound-guided biopsy of the prostate: a randomized, double-blind, placebocontrolled study. Urology 2003; 61: 585. 9. Seymour H, Perry MJA, Lee-Elliot C et al: Pain after transrectal ultrasonography-guided prostate biopsy: the advantages of periprostatic local anaesthesia. BJU Int 2001; 88: 540. 10. Von Knobloch R, Weber J, Varga Z et al: Bilateral fine needle administered local anaesthetic nerve block for pain control during TRUS-guided multicore prostate biopsy: a prospective randomised trial. Eur Urol 2002; 41: 508.
13. Ashley RA, Inman BA, Routh JC et al: Preventing pain during office biopsy of the prostate: a single center, prospective, double-blind, 3 arm, parallel group, randomized clinic trial. Cancer 2007; 110: 1708.
21. Irani J, Fournier F, Bon D et al: Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. BJU Int 1997; 79: 608. 22. Bulbul MA, Haddad MC, Khauli RB et al: Periprostatic infiltration with local anesthesia during transrectal ultrasound-guided prostate biopsy is safe, simple and effective: a pilot study. Clin Imaging 2002; 26: 129. 23. Hollabaugh RS, Dmochowski RR and Steiner MS: Neuroanatomy of the male rhabdosphincter. Urology 1997; 49: 426.
14. Raber M, Scattoni V, Roscigno M et al: Topical prilocaine-lidocaine cream combined with peripheral nerve block improve pain control in prostatic biopsy: results from a prospective randomized trial. Eur Urol 2008; 53: 967.
24. Yun TJ, Lee HJ, Kim SH et al: Does the intrarectal instillation of lidocaine gel before periprostatic neurovascular bundle block during transrectal ultrasound guided biopsies, improve analgesic effect? A prospective, randomized trial. J Urol 2007; 178: 103.
15. Giannarini G, Autorino R, Valent F et al: Combination of perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block for pain control during transrectal ultrasound guided biopsy: a randomized, controlled trial. J Urol 2009; 181: 585.
25. McCabe JE, Hanchanale VS, Philip J et al: A randomized controlled trial of topical glyceryl trinitrate before transrectal ultrasonography guided biopsy of the prostate. BJU Int 2007; 100: 536.
16. Cantiello F, Imperatore V, Iannuzzo MT et al: Periprostatic nerve block alone (PNB) vs PNB combined with an anesthetic-myorelaxant agent cream for prostate biopsy: a prospective randomized double arm study. BJU Int 2009; 103: 1195. 17. Wu CL, Carter B, Naqibuddin M et al: Effect of local anesthetic on patient recovery after transrectal biopsy. Urology 2001; 57: 925. 18. Akpinar H, Tüfek I, Atu˘g F et al: Doppler ultrasonography guided pelvic plexus block before systematic needle biopsy of the prostate: a prospective randomized study. Urology 2009; 74: 267.
26. Brooks JD: Anatomy of the lower urinary tract and male genitalia. In: Campbell’s Urology, 7th ed. Edited by MF Campbell, AB Retik, ED Vaughan Jr et al. Philadelphia: WB Saunders 1998; vol 1, pp 99 –100. 27. Schlegel PN and Walsh PC: Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol 1987; 138: 1402. 28. Walsh PC, Lepor H and Eggleston JC: Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 1983; 4: 473.
19. Statistics Toolbox User’s Guide. Natick: The Mathworks 2011.
29. Lee-Elliott CE, Dundas D and Patel U: Randomized trial of lidocaine vs lidocaine/bupivacaine periprostatic injection on longitudinal pain score after prostate biopsy. J Urol 2004; 171: 247.
20. Crundwell MC, Cooke PW and Wallace DMA: Patients’ tolerance of transrectal ultrasoundguided prostatic biopsy: an audit of 104 cases. BJU Int 1999; 83: 792.
30. Price D, Bush FM, Long S et al: A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain 1994; 56: 217.
EDITORIAL COMMENT TRUS guided prostate biopsy is probably the most common office based invasive urological procedure. However, strict standards have not yet been formulated. The number of cores and PSA cutoffs for bi-
opsy can vary greatly among urologists. Pain control is similarly a concern of ongoing debate. Nevertheless, some statements are widely accepted. 1) Prostate biopsy is a painful procedure and a form of
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anesthesia is a must. 2) Transrectal gel applications alone are insufficient for pain relief. 3) Currently periprostatic local anesthesia can be accepted as the gold standard anesthetic method and each new attempt should be compared against periprostatic blockage.1 4) The other major component of pain during prostate biopsy is initial probe insertion in the anus and transrectal gels can help lessen anal pain. 5) Since the best anesthetic technique remains to be established, new anesthetic methods can be proposed. For example, Mutaguchi et al described a reasonable alternative method, namely intraprostatic local anesthesia.2 Subsequently a prospective, randomized trial provided a better pain control when intraprostatic analgesia was combined with periprostatic analgesia.3 The current authors similarly addressed a new alternative to periprostatic application. PPB under Doppler ultrasound guidance was previously presented as an efficient form of anesthesia (reference 18 in article). In this study PPB clearly provided more effective pain control without an increase in
complications. This is the second trial proposing the superiority of PPB. In my opinion the major drawback of PPB is the need for Doppler ultrasound, which requires a relatively expensive instrument and is not widely available for an office based procedure. The other issue is the doubtful clinical relevance of the approximately 0.5 to 1-point lower VAS score during (VAS 3) and 30 minutes after (VAS 4) biopsy using PPB (see table). Lastly, a possible disadvantage of PPB during surgical dissection at subsequent radical prostatectomy should be investigated. Simultaneously PPB may be related to an increase in erectile dysfunction after radical prostatectomy. In conclusion, further trials in a large number of patients are required to draw a final conclusion about PPB. Kamil Cam Department of Urology Duzce University School of Medicine Duzce, Turkey
REFERENCES 1. Maccagnano C, Scattoni V, Roscigno M et al: Anaesthesia in transrectal prostate biopsy: which is the most effective technique? Urol Int 2011; 87: 1.
2. Mutaguchi K, Shinohara K, Matsubara A et al: Local anesthesia during 10 core biopsy of the prostate: comparison of 2 methods. J Urol 2005; 173: 742.
3. Cam K, Sener M, Kayikci A et al: Combined periprostatic and intraprostatic local anesthesia for prostate biopsy: a double-blind, placebo controlled, randomized trial. J Urol 2008; 180: 141.
REPLY BY AUTHOR Dr. Cam outlined some remarkable aspects of PPB. We believe that the higher cost of Doppler ultrasound must be weighed against the superior pain control of IRLA plus PPB, especially in younger patients and those with a larger prostate. However, cost-effectiveness analysis is strongly advocated in future trials, which may help choose the less expensive effective analgesic technique for daily practice. Concerning the second comment, we report a greater benefit in pain palliation during biopsy (VAS 3), which can be considered clinically meaningful. Studies of acute pain showed that a clinically meaningful variation in pain corresponds to a minimum 10 mm difference on a 100 mm VAS if scores are assigned
by patients.1,2 However, we agree that the 1-point difference may be questionable, especially when comparing low VAS scores, which are frequently reported during prostate biopsy performed with some form of anesthesia. Finally, whether anesthetic injection directly into the pelvic plexus results in more complicated nerve sparing radical prostatectomy must be investigated as well as whether it is related to increased erectile dysfunction after surgery. Further randomized trials in more patients are needed to evaluate the results and complications of this new technique and answer the open questions described.
REFERENCES 1. Kelly AM: Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Acad Emerg Med 1998; 5: 1086. 2. Gallager EJ, Liebman M and Bijur PE: Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med 2001; 38: 633.
Pelvic Plexus Block is More Effective than Periprostatic Nerve Block for Pain Control During Office Transrectal Ultrasound Guided Prostate Biopsy: A Single Center, Prospective, Randomized, Double Arm Study Francesco Cantiello,* Antonio Cicione, Riccardo Autorino, Carlo Cosentino, Francesco Amato and Rocco Damiano From the Urology Unit (FC, AC, RD) and School of Biomedical Engineering (CC, FA), Magna Græcia University of Catanzaro, Catanzaro, Italy, and Center for Laparoscopic and Robotic Surgery, Cleveland Clinic (RA), Cleveland, Ohio
Purpose: We compared intrarectal local anesthesia plus pelvic plexus block vs intrarectal local anesthesia plus periprostatic nerve block during transrectal ultrasound guided prostate biopsy. Materials and Methods: Patients were randomized 1:1 by a computer generated schedule into group 1—90 who received intrarectal local anesthesia (lidocaine 1.5%-nifedipine 0.3% cream) plus pelvic plexus block (2.5 ml lidocaine 1% plus naropine 0.75% injected on each side into the pelvic neurovascular plexus lateral to the seminal vesicle tip) and group 2—90 who received intrarectal local anesthesia plus periprostatic nerve block (2.5 ml of the same mixture injected on each side into the neurovascular bundles at the prostate-bladder-seminal vesicle angle) before transrectal ultrasound guided prostate biopsy. After the procedure patients were instructed to rate the level of pain/discomfort from 0 to 10 on the visual analog scale at certain time points, including during the introduction and presence of the probe in the rectum, during pelvic plexus block or periprostatic nerve block, during biopsy and 30 minutes after biopsy. Results: The 2 groups were similar in age, serum prostate specific antigen and total prostate volume. There was no difference in pain perception during probe introduction and pelvic plexus or periprostatic nerve block. Pain during prostate biopsy was significantly lower in group 1 than in group 2 (p ⬍0.001). The same trend was recorded for pain perception 30 minutes after biopsy (p ⫽ 0.001). There were no major complications. Conclusions: Pelvic plexus block under Doppler ultrasound guidance provides better analgesia than periprostatic nerve block during office based transrectal ultrasound guided prostate biopsy.
Abbreviations and Acronyms IRLA ⫽ intrarectal local anesthesia PNB ⫽ periprostatic nerve block PPB ⫽ pelvic plexus block PSA ⫽ prostate specific antigen TRUS ⫽ transrectal ultrasound VAS ⫽ visual analog scale Submitted for publication December 5, 2011. Study received institutional review board approval. * Correspondence: Urology Unit, Magna Græcia University of Catanzaro, Viale Europa, Germaneto, Catanzaro 88100, Italy (telephone: ⫹39 338 7914352; e-mail: [email protected]).
Key Words: prostate; biopsy; ultrasound, high-intensity focused, transrectal; pain; analgesia TRANSRECTAL ultrasound guided biopsy is the standard procedure for diagnosing prostate cancer. However, to date the most efficient biopsy scheme with the optimal number and location of cores has not yet been defined.1,2
Different forms of anesthesia have been used to make TRUS guided prostate biopsy a more comfortable procedure.3 PNB is simple, easy to perform, highly effective and widely considered the preferred method for pain control.4 –11
0022-5347/12/1882-0417/0 THE JOURNAL OF UROLOGY® © 2012 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
http://dx.doi.org/10.1016/j.juro.2012.04.003 Vol. 188, 417-422, August 2012 RESEARCH, INC. Printed in U.S.A
AND
www.jurology.com
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Prostate biopsy related pain has a dual origin, including the introduction and manipulation of the TRUS probe into anal canal and rectum, and needle passage through the prostate capsule.12 PNB alone cannot completely eliminate discomfort since it does not affect TRUS probe related pain. Thus, to optimize pain control additional IRLA before PNB was suggested.13–16 PPB is a more recently described method of local anesthesia and only 2 studies have been reported.17,18 In 1 study encouraging results were achieved with decreased pain during local anesthetic injection and prostate sampling compared to PNB.18 We report a prospective, randomized study comparing IRLA plus PPB vs IRLA plus PNB during TRUS guided prostate biopsy.
MATERIALS AND METHODS Study Design After receiving institutional review board approval this prospective, randomized, double arm trial was done at a tertiary care institution (Magna Græcia University, Catanzaro, Italy) between October 2010 and October 2011. Study inclusion criteria were PSA 4 ng/ml or greater, abnormal digital rectal examination and/or a TRUS suspicious lesion. Exclusion criteria were previous prostate biopsies, chronic prostatitis, chronic pelvic pain syndrome, inflammatory bowel disease, anorectal fissure/fistula, active urinary tract infection, bleeding disorder, and allergy to local anesthetic and myorelaxant agents. A total of 180 patients agreed to participate and provided informed consent. They were enrolled and randomized 1:1 by a computer generated schedule (see figure).
Treatment Allocation Patients were randomly assigned to 1 of 2 groups, including group 1—IRLA plus PPB and group 2—IRLA plus PNB before TRUS guided prostate biopsy. They were blinded to treatment group assignment.
Biopsy Procedure Anticoagulation or antiaggregant therapy was discontinued 7 days before biopsy. As antibiotic prophylaxis, oral
administration of levofloxacin 500 mg daily was administered starting the evening before the procedure until 4 days after the procedure. A cleaning enema was administered the evening before and the morning of biopsy. An SSD 5000 ultrasound scanner (Aloka, Wallingford, Connecticut) with a 7.5 MHz endorectal multiplanar end fire probe was used. The probe was rectilinear with a basal and middle part diameter of 16 mm and an apical diameter (corresponding transducer) of 18 mm. Before biopsy prostate volume was measured using the formula for an ellipse. As IRLA, in each group 10 ml lidocaine 1.5%-nifedipine 0.3% anesthetic-myorelaxant cream was applied around the anal ring, and in the anus and rectum 10 minutes before introducing the TRUS probe. Thereafter 22 gauge 20 cm spinal needle was used to inject 5 ml of a mixture of lidocaine 1% and naropine 0.75%. In group 1 with PPB 2.5 ml of the mixture were injected on each side into the pelvic neurovascular plexus lateral to the tip of the seminal vesicles under echo color Doppler guidance.17,18 In group 2 with PNB 2.5 ml of the mixture were injected on each side into the neurovascular bundles at the prostate-bladderseminal vesicle angle.4 –11 After 5 minutes prostate biopsies were performed with an automatic, spring loaded disposable biopsy gun and an 18 gauge Tru-Cut® needle by the same single operator using a 12-core scheme, including 6 parasagittal and 6 lateral cores covering the base, mid zone and apex bilaterally, with the patient in the lithotomy position. Additional cores were obtained from the area of suspected malignancy.
Pain and Complication Assessment All patients were hospitalized in our 1-day surgery center and observed for 2 hours after the procedure. They were discharged home only if they voided successfully. During the hospital stay patients were instructed by a resident blinded to the analgesia received to rate the level of pain/ discomfort from 0 to 10 on the VAS at certain time points, including during VAS 1—introduction and presence of the probe in the rectum, VAS 2—pelvic plexus block or periprostatic nerve block, VAS 3— biopsy procedure and VAS 4 —30 minutes after the procedure. Patients were also blinded to the local anesthetic injection site.
Consolidated Standard of Reporting Trials flow diagram of study participants
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The parameters recorded were biopsy related complications and the prostate cancer detection rate. Patients were given a nonvalidated self-administered questionnaire, which was completed at home in regard to complications and collected on day 14 after biopsy, when they returned for histological findings. Complications were graded as severe— hypotension or lipothymia/syncope requiring intravenous therapy, allergic reaction, hematuria and rectal bleeding requiring hospitalization, acute urinary retention and urosepsis with fever greater than 38.5C, and mild—self-limiting hematuria and/or rectal bleeding and hemospermia.
Statistical Analysis The primary end point was efficacy, as assessed by the VAS. A minimum 1-point difference in the 10-point VAS score is generally considered clinically significant when scores are assigned by patients.15 Based on a previous study comparing PPB and PNB sample size was calculated by assuming an SD of the VAS score at the prostate sampling step (VAS 3) equal to 1.95 in the PPB group and 2.16 in the PNB group,18 which yielded an average SD of 2.06. To detect a 1-point difference with 90% power and 2-sided 5% significance the study required a minimum of 180 patients randomized 1:1 in 2 arms. Differences in mean VAS scores were calculated using the Student t test with p ⬍0.05 considered statistically significant. All data were analyzed using Statistics Toolbox™.19 Analysis was done by intent to treat.
RESULTS The 2 groups were similar in age, serum PSA, total prostate volume and cancer detection rate (see table). Cancer was detected in 31 of 90 men (34.4%) with PPB and in 28 of 90 (31.1%) with PNB (Fisher exact test p ⫽ 0.75). Pain perception during probe insertion was similar in the 2 groups (p ⫽ 0.198). Similarly there was no difference in pain perception during PPB or PNB (p ⫽ 0.749). Pain during prostate biopsy was significantly lower in group 1 with PPB than in group 2 with PNB (p ⬍0.001). A significant difference was also noted for pain perception 30 minutes after biopsy (p ⫽ 0.001, see table). No side effects associated with local anesthesia and no modification of cardiovascular parameters
Patient characteristics and pain on VAS in groups 1 and 2 Mean ⫾ SD Group 1 Age PSA (ng/ml) Prostate vol (ml) VAS (time): 1 (probe insertion) 2 (PPB or PNB) 3 (biopsy) 4 (after 30 mins)
63.7 ⫾ 5.4 7.5 ⫾ 3.4 45.8 ⫾ 7.7 1.36 ⫾ 0.53 1.32 ⫾ 0.71 2.28 ⫾ 0.84 2.02 ⫾ 0.82
Mean ⫾ SD Group 2 63.2 ⫾ 5.5 8.5 ⫾ 4.5 47.5 ⫾ 10.9 1.22 ⫾ 1.34 ⫾ 3.37 ⫾ 2.41 ⫾
0.44 0.69 0.78 0.76
p Value (Student t test) 0.539 0.094 0.209 0.198 0.749 ⬍0.001 0.001
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were observed. There were no major complications. Two patients per group with prostatic hypertrophy were catheterized due to urinary retention after biopsy. In a group 1 patient there was fever greater than 38C, which was treated at home with intravenous antibiotics. There was no difference in PPB and PNB performance time.
DISCUSSION Prostate biopsy is associated with significant pain in approximately a fourth of patients20,21 and many who do not receive adequate anesthesia may refuse further TRUS biopsy, if needed.21,22 Pain during biopsy is mainly caused by the introduction and manipulation of the ultrasound probe in the anal canal and rectum, and needle penetration into the prostate capsule, which is richly innervated with autonomic sympathetic and parasympathetic fibers.4,23 Current evidence suggests that the PNB is safe, easy to perform and effectively decreases pain and discomfort in patients who undergo TRUS guided prostate biopsy.5–11 However, PNB does not completely eliminate pain since it cannot affect the discomfort related to TRUS probe manipulation, which may be more painful than biopsy.12 Thus, IRLA is required to decrease the pain associated with the TRUS probe in the first part of the biopsy procedure. The optimum would be a combination of IRLA plus PNB since the 2 components of the biopsy associated pain process, that is probe manipulation and prostate capsule puncturing, would be affected. Several studies have shown the superiority of combined anesthesia compared to PNB alone. Raber et al noted that PNB with perianal-intrarectal lidocaine-prilocaine cream compared to PNB alone significantly decreased pain during TRUS probe introduction and periprostatic anesthetic injection, although pain during biopsy was not decreased.14 Giannarini et al reported that the combination of PNB and perianal-intrarectal lidocaine-prilocaine cream was superior to PNB alone during all biopsy phases.15 Yun et al observed that additional instillation of intrarectal lidocaine gel before PNB provided effective higher analgesia than PNB alone but only during biopsy sampling while during PNB and 20 minutes after biopsy there was no statistically significant difference.24 They did not measure pain associated with TRUS probe introduction. Recently IRLA was achieved using myorelaxant cream to decrease anal sphincter tone and consequently the pain related to TRUS probe introduction. McCabe et al reported that PNB combined with perianal-intrarectal 0.2% glyceryl trinitrate paste compared to PNB with placebo significantly decreased the pain associated with TRUS guided biopsy, particularly during TRUS probe introduction.25
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In our previous study combined lidocaine-nifedipine cream topically placed with PNB was superior to PNB alone for decreasing pain and discomfort during TRUS probe introduction and PNB, and 30 minutes after biopsy.16 PPB was recently described as effective analgesia during TRUS guided prostate biopsy.17,18 The autonomic pelvic plexus consists of sympathetic and parasympathetic fibers. It is rectangular and 3 to 5 cm long, and its midpoint is at the tips of the seminal vesicles. It courses on either side of the rectum and is penetrated by numerous vessels going to and from the rectum, bladder, seminal vesicles and prostate. These vessels represent the lateral pedicles of the bladder and prostate, and cross sectioning them can damage the pelvic plexus, causing relative iatrogenic impotence. In fact, the pelvic plexus gives rise to the innervation of the prostate and cavernous nerves with the most caudal portion, that is the prostatic plexus.26,27 The prostatic plexus courses with the prostatic vascular strictures as the neurovascular bundle at the posterolateral border of the prostate. These posterolateral fibers are thought to be the main nerve supply of the prostate since only a few nerve fibers are situated on the superolateral and anterior surfaces of the prostate.18,23,26,28 PPB was first described by Wu et al.17 They injected 5 ml 1% lidocaine lateral to the tip of the seminal vesicles under grayscale ultrasound guidance. This procedure did not decrease biopsy associated pain. Later more promising results were reported by Akpinar et al.18 In a single center, prospective, randomized study they compared the efficacy of PNB with that of PPB (2 ml 2% lidocaine on each side). They noted a significantly lower VAS pain score in the PPB group during local anesthetic injection (3.12 vs 2.05, p ⫽ 0.0007) and prostate sampling (4.97 vs 2.7, p ⬍0.001). The reason for the different findings in the study by Wu et al17 and that by Akpinar et al18 may relate to the smaller, higher concentration of local anesthesia in the latter with a briefer injection time and by the use of Doppler ultrasound with more precise localization of the pelvic plexus. We performed IRLA with a lidocaine 1.5%-nifedipine 0.3% cream and achieved a low VAS pain score during TRUS probe introduction in each group. This cream is a mixture of a topical, short acting anesthesia and a myorelaxant agent, designed to provide 12-hour palliation of the symptoms of anal rhagades. This leads to better pain control during TRUS probe introduction due to the anesthetic and myorelaxant effects, and to longer lasting palliation of discomfort due to the pharmacokinetics of the drug and its duration of action. VAS 2 pain scores for PPB or PNB were similar to those reported in the literature for groups 1 and
2.15,16,18,24 Also, patients who received PPB experienced less pain than those who received PNB during prostate sampling and 30 minutes after biopsy. PPB may provide better anesthesia because its action is proximal to the prostate with a block of more nerve fibers. In fact, PPB affects all sensory nerve fibers of the prostatic plexus, including fibers that enter the prostatic capsule at the base, superolateral and anterior surfaces. However, the VAS 3 (biopsy) result was higher than in the current literature. This may have been due to the small amount of local anesthesia (2.5 ml of a mixture of lidocaine 1% and naropine 0.75% on each side). We used a small amount of local anesthesia injected several cm away from 2 points (tip of the seminal vesicle and the prostate-bladder-seminal vesicle angle) to avoid spreading anesthesia along the nerve fibers, which seemed likely for this higher anesthetic volume. We do not think that VAS 3 pain scores were influenced by the time between anesthetic injection and biopsy (5 minutes). We used a mixture of lidocaine 1% and naropine 0.75%, that is a short and a long acting anesthesia, to avoid the rebound pain effect. Lee-Elliot et al addressed the rebound pain effect using lidocaine alone.29 In a randomized trial comparing lidocaine vs lidocaine and a long acting anesthetic periprostatic injection the combination significantly attenuated the 1-hour rebound pain noted after the short acting anesthesia alone. Our study was not powered to perform such subanalysis. Thus, specific assessment with patient stratification based on age was not done. However, similar to that reported by others,15,24 we perceived that older patients and those with a smaller prostate seemed to have lower VAS pain scores. Doppler ultrasound allows precise delivery of local anesthesia to the pelvic plexus area, avoiding violation of the vascular structures and contributing to the low rate of complications, particularly vascular complications, associated with this technique without causing longer application time.18 The higher cost of combined analgesia and Doppler ultrasound is a serious concern, given the exponentially growing number of procedures performed worldwide. This economic limitation must be weighed against the superior pain control of IRLA plus PPB compared to that of IRLA plus PNB or a single analgesia. Cost-effectiveness analysis is strongly advocated to specifically address this issue. Placebo, no intervention and IRLA alone arms were not included in this study, given the strong evidence that combined anesthesia decreases the pain associated with biopsy.14,16 Further studies are needed to determine whether PPB results in more adhesions, which would make
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the surgical steps more difficult, and whether it interferes with normal recovery of erectile function and urinary continence after surgery. Finally, a VAS is often used in epidemiological and clinical studies, and its strengths and weaknesses are well evaluated.30 Although a VAS is far
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from being an accurate scientific and reproducible tool, to our knowledge there is currently no better way to compare the anesthetic effect during prostate biopsy. In conclusion, PPB under Doppler ultrasound guidance provides better analgesia than PNB during office based TRUS guided prostate biopsy.
REFERENCES 1. Heidenreich A, Bellmunt J, Bolla M et al: EAU guidelines on prostate cancer. Part 1: screening, diagnosis and treatment of clinically localized disease. Eur Urol 2011; 59: 61.
11. Kaver I, Mabjeesh NJ and Matzkin H: Randomized prospective study of periprostatic local anesthesia during transrectal ultrasound-guided prostate biopsy. Urology 2002; 59: 405.
2. Scattoni V, Raber M, Capitanio U et al: The optimal rebiopsy prostati scheme depends on patient clinical characteristics: results of a recursive partitioning analysis based on a 24-core systematic scheme. Eur Urol 2011; 60: 834.
12. Luscombe CJ and Cooke PW: Pain during prostate biopsy. Lancet 2004; 363: 1840.
3. Autorino R, De Sio M, Di Lorenzo G et al: How to decrease pain during transrectal ultrasound guided prostate biopsy: a look at the literature. J Urol 2005; 174: 2091. 4. Nash PA, Bruce JE, Indudhara R et al: Transrectal ultrasound guided prostatic nerve blockade eases systematic needle biopsy of the prostate. J Urol 1996; 155: 607. 5. Soloway MS and Obek C: Periprostatic local anesthesia before ultrasound guided biopsy. J Urol 2000; 163: 172. 6. Lynn NN, Collins GN, Brown SC et al: Periprostatic nerve block gives better analgesia for prostatic biopsy. BJU Int 2002; 90: 424. 7. Leibovici D, Zisman A, Siegel YI et al: Local anesthesia for prostate biopsy by periprostatic lidocaine injection: a double-blind placebo controlled study. J Urol 2002; 167: 563. 8. Berger AP, Frauscher F, Halpern EJ et al: Periprostatic administration of local anesthesia during transrectal ultrasound-guided biopsy of the prostate: a randomized, double-blind, placebocontrolled study. Urology 2003; 61: 585. 9. Seymour H, Perry MJA, Lee-Elliot C et al: Pain after transrectal ultrasonography-guided prostate biopsy: the advantages of periprostatic local anaesthesia. BJU Int 2001; 88: 540. 10. Von Knobloch R, Weber J, Varga Z et al: Bilateral fine needle administered local anaesthetic nerve block for pain control during TRUS-guided multicore prostate biopsy: a prospective randomised trial. Eur Urol 2002; 41: 508.
13. Ashley RA, Inman BA, Routh JC et al: Preventing pain during office biopsy of the prostate: a single center, prospective, double-blind, 3 arm, parallel group, randomized clinic trial. Cancer 2007; 110: 1708.
21. Irani J, Fournier F, Bon D et al: Patient tolerance of transrectal ultrasound-guided biopsy of the prostate. BJU Int 1997; 79: 608. 22. Bulbul MA, Haddad MC, Khauli RB et al: Periprostatic infiltration with local anesthesia during transrectal ultrasound-guided prostate biopsy is safe, simple and effective: a pilot study. Clin Imaging 2002; 26: 129. 23. Hollabaugh RS, Dmochowski RR and Steiner MS: Neuroanatomy of the male rhabdosphincter. Urology 1997; 49: 426.
14. Raber M, Scattoni V, Roscigno M et al: Topical prilocaine-lidocaine cream combined with peripheral nerve block improve pain control in prostatic biopsy: results from a prospective randomized trial. Eur Urol 2008; 53: 967.
24. Yun TJ, Lee HJ, Kim SH et al: Does the intrarectal instillation of lidocaine gel before periprostatic neurovascular bundle block during transrectal ultrasound guided biopsies, improve analgesic effect? A prospective, randomized trial. J Urol 2007; 178: 103.
15. Giannarini G, Autorino R, Valent F et al: Combination of perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block for pain control during transrectal ultrasound guided biopsy: a randomized, controlled trial. J Urol 2009; 181: 585.
25. McCabe JE, Hanchanale VS, Philip J et al: A randomized controlled trial of topical glyceryl trinitrate before transrectal ultrasonography guided biopsy of the prostate. BJU Int 2007; 100: 536.
16. Cantiello F, Imperatore V, Iannuzzo MT et al: Periprostatic nerve block alone (PNB) vs PNB combined with an anesthetic-myorelaxant agent cream for prostate biopsy: a prospective randomized double arm study. BJU Int 2009; 103: 1195. 17. Wu CL, Carter B, Naqibuddin M et al: Effect of local anesthetic on patient recovery after transrectal biopsy. Urology 2001; 57: 925. 18. Akpinar H, Tüfek I, Atu˘g F et al: Doppler ultrasonography guided pelvic plexus block before systematic needle biopsy of the prostate: a prospective randomized study. Urology 2009; 74: 267.
26. Brooks JD: Anatomy of the lower urinary tract and male genitalia. In: Campbell’s Urology, 7th ed. Edited by MF Campbell, AB Retik, ED Vaughan Jr et al. Philadelphia: WB Saunders 1998; vol 1, pp 99 –100. 27. Schlegel PN and Walsh PC: Neuroanatomical approach to radical cystoprostatectomy with preservation of sexual function. J Urol 1987; 138: 1402. 28. Walsh PC, Lepor H and Eggleston JC: Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 1983; 4: 473.
19. Statistics Toolbox User’s Guide. Natick: The Mathworks 2011.
29. Lee-Elliott CE, Dundas D and Patel U: Randomized trial of lidocaine vs lidocaine/bupivacaine periprostatic injection on longitudinal pain score after prostate biopsy. J Urol 2004; 171: 247.
20. Crundwell MC, Cooke PW and Wallace DMA: Patients’ tolerance of transrectal ultrasoundguided prostatic biopsy: an audit of 104 cases. BJU Int 1999; 83: 792.
30. Price D, Bush FM, Long S et al: A comparison of pain measurement characteristics of mechanical visual analogue and simple numerical rating scales. Pain 1994; 56: 217.
EDITORIAL COMMENT TRUS guided prostate biopsy is probably the most common office based invasive urological procedure. However, strict standards have not yet been formulated. The number of cores and PSA cutoffs for bi-
opsy can vary greatly among urologists. Pain control is similarly a concern of ongoing debate. Nevertheless, some statements are widely accepted. 1) Prostate biopsy is a painful procedure and a form of
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anesthesia is a must. 2) Transrectal gel applications alone are insufficient for pain relief. 3) Currently periprostatic local anesthesia can be accepted as the gold standard anesthetic method and each new attempt should be compared against periprostatic blockage.1 4) The other major component of pain during prostate biopsy is initial probe insertion in the anus and transrectal gels can help lessen anal pain. 5) Since the best anesthetic technique remains to be established, new anesthetic methods can be proposed. For example, Mutaguchi et al described a reasonable alternative method, namely intraprostatic local anesthesia.2 Subsequently a prospective, randomized trial provided a better pain control when intraprostatic analgesia was combined with periprostatic analgesia.3 The current authors similarly addressed a new alternative to periprostatic application. PPB under Doppler ultrasound guidance was previously presented as an efficient form of anesthesia (reference 18 in article). In this study PPB clearly provided more effective pain control without an increase in
complications. This is the second trial proposing the superiority of PPB. In my opinion the major drawback of PPB is the need for Doppler ultrasound, which requires a relatively expensive instrument and is not widely available for an office based procedure. The other issue is the doubtful clinical relevance of the approximately 0.5 to 1-point lower VAS score during (VAS 3) and 30 minutes after (VAS 4) biopsy using PPB (see table). Lastly, a possible disadvantage of PPB during surgical dissection at subsequent radical prostatectomy should be investigated. Simultaneously PPB may be related to an increase in erectile dysfunction after radical prostatectomy. In conclusion, further trials in a large number of patients are required to draw a final conclusion about PPB. Kamil Cam Department of Urology Duzce University School of Medicine Duzce, Turkey
REFERENCES 1. Maccagnano C, Scattoni V, Roscigno M et al: Anaesthesia in transrectal prostate biopsy: which is the most effective technique? Urol Int 2011; 87: 1.
2. Mutaguchi K, Shinohara K, Matsubara A et al: Local anesthesia during 10 core biopsy of the prostate: comparison of 2 methods. J Urol 2005; 173: 742.
3. Cam K, Sener M, Kayikci A et al: Combined periprostatic and intraprostatic local anesthesia for prostate biopsy: a double-blind, placebo controlled, randomized trial. J Urol 2008; 180: 141.
REPLY BY AUTHOR Dr. Cam outlined some remarkable aspects of PPB. We believe that the higher cost of Doppler ultrasound must be weighed against the superior pain control of IRLA plus PPB, especially in younger patients and those with a larger prostate. However, cost-effectiveness analysis is strongly advocated in future trials, which may help choose the less expensive effective analgesic technique for daily practice. Concerning the second comment, we report a greater benefit in pain palliation during biopsy (VAS 3), which can be considered clinically meaningful. Studies of acute pain showed that a clinically meaningful variation in pain corresponds to a minimum 10 mm difference on a 100 mm VAS if scores are assigned
by patients.1,2 However, we agree that the 1-point difference may be questionable, especially when comparing low VAS scores, which are frequently reported during prostate biopsy performed with some form of anesthesia. Finally, whether anesthetic injection directly into the pelvic plexus results in more complicated nerve sparing radical prostatectomy must be investigated as well as whether it is related to increased erectile dysfunction after surgery. Further randomized trials in more patients are needed to evaluate the results and complications of this new technique and answer the open questions described.
REFERENCES 1. Kelly AM: Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? Acad Emerg Med 1998; 5: 1086. 2. Gallager EJ, Liebman M and Bijur PE: Prospective validation of clinically important changes in pain severity measured on a visual analog scale. Ann Emerg Med 2001; 38: 633.