Introduction and History
Transrectal ultrasound-guided prostate biopsy is one of the most common procedures performed by urologists. Over the past decade, one of the most significant developments has been the ability to provide local anesthesia to patients undergoing this procedure.
Injection of a local anesthetic into the perineum was standard when transperineal prostate biopsy was the common approach, but this type of anesthesia was abandoned when transrectal biopsy under ultrasound guidance became possible. Because the rectal mucosa was neither easily accessible to direct an injection nor considered sensate above the dentate line, urologists readily accepted the idea that anesthesia was no longer necessary for prostate biopsy.
Initially, biopsies involved taking a limited number of cores from a nodule, but Hodge et al changed that approach in 1989, with the sextant biopsy technique, which soon became the standard for most urologists.  By the time the sixth core was obtained, however, many patients reported pain.
Over time, 8-14 became the standard number of cores obtained, and many patients began to voice dissatisfaction. Although many urologists continued to believe that prostate biopsy was painless, up to 96% of patients disagreed. In one study, 1 in 5 patients said that they would refuse to undergo the procedure again without anesthesia. 
Most urologists have observed that it is much easier to convince a patient to undergo an initial prostate biopsy than it is to convince a patient to undergo repeat biopsy. Published reports suggest that up to one third of patients refuse the recommendation for repeat biopsy because of associated pain.
In 1996, Nash et al described the use of local anesthesia for prostate biopsy via a periprostatic block.  However, until Soloway and Obek published a corroborating study in 2000,  few urologists opted to change their prostate biopsy procedure. Over 45 studies have now validated periprostatic block as an effective technique to block the pain of prostate biopsy.
A normal prostate gland is approximately 20 g in volume, 3 cm in length, 4 cm wide, and 2 cm in depth. As men get older, the prostate gland is variable in size secondary to benign prostatic hyperplasia. The gland is located posterior to the pubic symphysis, superior to the perineal membrane, inferior to the bladder, and anterior to the rectum. The base of the prostate is in continuity with the bladder and the prostate ends at the apex before becoming the striated external urethral sphincter. The sphincter is a vertically oriented tubular sheath that surrounds the membranous urethra and prostate.
The anal canal is the most terminal part of the lower GI tract/large intestine, which lies between the anal verge (anal orifice, anus) in the perineum below and the rectum above. In anatomy texts, the rectum changes to the anal canal at the dentate line. For surgeons, however, the demarcation between the rectum above and the anal canal below is the anorectal ring. The anal canal is completely extraperitoneal. The length of the (surgical) anal canal is about 3-5 cm, with two thirds of this being above the dentate line and one third below the dentate line (anatomical anal canal).
Patient Preparation and Positioning
Patient comfort is an important factor in transrectal ultrasound-guided prostate biopsy. Respect for the patient's modesty is medicolegally advisable. The following methods are helpful in providing comfort for the patient:
Placing sheets over the patient's legs to allow him to feel some control over an embarrassing situation
Designing the examining room layout to minimize the chance of someone opening the door and seeing the patient in an embarrassing position
Positioning the examining table so that the patient's private body areas are not visible from the door
Having doors that open in a manner that prevents the patient from being seen by a visitor until the door is completely opened (provides a time delay for any misdirected visitor to stop if errantly entering the room)
Having curtains in front of the door so that the patient feels less vulnerable
Setting the temperature of the examining room at a level that accommodates a partially clothed patient
Patient positioning is influenced by the type of ultrasound probe used. The two types of probes include the end-fire probe (see the first 2 images below) and the side-fire probe (see the second 2 images below). The two probes provide entirely different views and require different techniques; if the technique for one probe is used for the other, confusion and disorientation will result when trying to identify specific areas via ultrasound.
See the list below:
The side-fire probe: Side-fire probes project laterally. For this reason, twisting the probe while keeping its axis neutral with respect to the sagittal plane laterally enables lateral visualization. Thus, a side-fire probe should remain essentially in the midline, twisting to reach the lateral aspects. This makes patient positioning relatively unimportant, as long as the anus is accessible.
The end-fire probe: The end-fire probe projects an imaging plane either directly or at a slight angle from the end of the probe. The probe handle must therefore be directed away from the side of interest to visualize the lateral areas, using the anus as a fulcrum to gain accurate placement (ie, the handle is moved downward, toward the patient's dependent left side, to visualize the right side of the prostate, and vice versa). The patient must be positioned with the buttocks on the edge of the examination table to allow the probe handle to be dropped far enough to reach beneath the plane of the examination table when the right lateral border of the prostate is visualized. This is most readily accomplished if the buttocks are positioned directly over the corner of the table.
Either type of probe allows optimal imaging if the patient's legs are flexed toward his chest and held up by the table extension; this can be facilitated by placing a pillow under one or both legs.
Limited visualization of the lateral aspects using either probe can result in two problems, as follows:
Periprostatic block is performed laterally where the periprostatic nerves approach the prostate.
The lateral aspects of the peripheral zone are the areas most likely to harbor cancer, so limiting such access raises the possibility of inadequate biopsies.
The authors find that the end-fire probe has the following two advantages over the side-fire probe:
Lateral visualization is more readily achieved with the end-fire probe, although the authors routinely perform prostate biopsies successfully with both probes.
With the end-fire probe, the needle exits its guide in a trajectory more directly toward the prostate instead of tangentially. This allows easier biopsy of the apex and anterior horn of the peripheral zone, further minimizing the possibility of a false-negative biopsy result.
Optimizing Probe Placement
The pain of intrarectal probe placement has traditionally been an overlooked aspect of transrectal ultrasound-guided prostate biopsy. Most modern ultrasound probes are reasonably sized—some no larger than an examining finger—so size alone should not cause undue pain. However, biopsy guides and irregularly shaped ends cause pain in many men.
Lubrication of urologic instruments is vital. The value of anesthetic-based lubricants has not been demonstrated, but the role of lubrication to minimize the shearing forces of friction against rectal mucosa is undeniable.
Probe placement should be controlled, with attention paid to patient comfort.
Apply light but slowly increasing pressure against the probe as its tapered end dilates the sphincter during entry. The anal canal may be oriented slightly in varying anatomic directions; this technique allows the probe to find the route of least resistance, thereby minimizing pain.
Hold the end of the probe between the thumb and forefinger. This allows greater range of motion than does a tight-fisted ("tennis racquet") grip and facilitates the biopsy procedure for the surgeon.
Ask the patient to breathe in and out slowly or to bear down in a manner similar to having a bowel movement.
Respectfully recognize the embarrassing nature of the procedure.
Gentle finger dilation followed by a change of examination glove can also facilitate sphincter relaxation.
The authors have found that, with local prostatic anesthesia, the biopsy-related pain is reduced to such an extent that the discomfort of placement of the probe is actually considered by patients to be twice as severe as the pain associated with the biopsy itself.
The physician should remain mindful of the topical anatomy throughout the procedure. Just as the laparoscopic surgeon observes the body during instrument entry and exit, the urologist or ultrasonographer should be observant that the probe should point in the direction of the rectal course during probe placement.
Analgesia for the sphincter has been elusive because of the circuitous route of the inferior rectal nerve. It exits through the Alcock canal and divides into branches beneath the levator ani, so that injection of adequate amounts of local anesthetic would cause more pain than probe insertion. Topical analgesics and intrarectal diclofenac have been described.
Options for Anesthesia
Before periprostatic block was described, the only reliable method for pain elimination during prostate biopsy was general or regional anesthesia. Some centers, particularly in Europe, continue to use general or regional anesthesia or to use systemic Entonox. However, the cost, time, operating room resources, and paperwork associated with general and regional anesthesia are rarely worthwhile. Moreover, patients must take time off from work and must have a designated driver to take them home.
Pain control has been reported with intrarectal lidocaine,  but other investigators have found no benefit. The theory behind using intrarectal lidocaine seems flawed. As noted, intrarectal diclofenac has also been described. Many medications are administered intrarectally, but the mechanism of action involves absorption of the medication into the hemorrhoidal circulation. Thus, the medication is unlikely to cross through the rectal wall and into the periprostatic nerves.
Topical anesthesia with prilocaine-lidocaine cream applied to the anal ring, anal canal, and anterior rectal wall can also improve pain scores, particularly during probe insertion and administration of periprostatic block. A randomized study demonstrated improved visual analog pain scores at those two time points but did not show that pain was improved during the during performance of the biopsy itself. [6, 7]
These agents potentially decrease pain sensation from rectal fibers, but these fibers do not exist above the dentate line in most patients, so they are not involved in pain sensation at most of the biopsy sites. The authors have found that some patients can sense rectal mucosal pain apparently because of atypical sensation above the dentate line. Anecdotally, intrarectal lidocaine fails to provide additional comfort during biopsy in more than 99.5% of cases.
Periprostatic injection of local anesthetic has found the most acceptance, and it is supported by more than 45 peer-reviewed articles. Short-acting lidocaine is the subject of most of these articles, but the authors have also demonstrated that bupivacaine injection (Marcaine) or a combination of Marcaine and lidocaine is as effective as lidocaine alone, and onset of action is as rapid as that for lidocaine. Whether the longer duration of action of Marcaine offers a benefit has not yet been demonstrated; however, this agent may play a role in local anesthesia for more involved prostatic procedures. 
Periprostatic Block: Mount Everest Technique
All current periprostatic block techniques are based on the original technique reported by Nash et al in 1996.  The authors' minimally modified technique, called the Mount Everest technique, is described as follows:
The probe is adjusted to the sagittal plane, with the on-screen biopsy guide operational before placement.
A 22-gauge, 7-inch spinal needle is placed through the biopsy guide channel under ultrasound guidance into the area where the prostatic innervation enters the gland (see below).
The probe is angled laterally until the notch between the prostate and the seminal vesicle is visualized. The fat in this notch is present in all patients and creates what the authors call the "Mount Everest sign," (shown below) because it has a white pyramidal appearance. Lidocaine (5 mL) is injected on each side.
Successful placement of the needle is confirmed when the injectate causes a separation of the seminal vesicles and prostate from the rectal wall (the ultrasonic wheal, as shown below).
Directing the anesthetic to the proper plane is facilitated by injecting the anesthetic as the needle enters the space, so as to expand its distance, and then pulling back slightly to open the potential space until anesthetic is seen dissecting caudally, as depicted in the images below. The space between the rectal wall and the prostate widens when the anesthetic dissects this plane. This can be accomplished by an injection at the base, the midgland, or the apex of the prostate.
Ultrasound examination and volume calculation are then performed per routine. There is no reason to delay biopsy, as lidocaine has an onset of action that is essentially immediate.
Difficulty finding the Mount Everest notch immediately upon probe placement results because of either inadequate depth of probe placement (easily remediable) or inadequate ultrasound visualization laterally, often because an inexperienced user is twisting the end-fire probe (the technique for the side-fire probe) or angling the side-fire probe (the technique for the end-fire probe), which leads to loss of bearings and perspective. The authors find that users new to the technique often do not place the probe deeply enough to easily position the biopsy guide into the large target area that the Mount Everest notch affords. In addition, failure to maintain direct contact of the probe against the rectal wall limits visualization and sacrifices the benefits of improved hemostasis through probe tamponade.
More than 45 published reports have verified the effectiveness of periprostatic block. The only study that has failed to report an advantage with this technique involved the injection of the anesthetic at the tip of the seminal vesicle instead of into the periprostatic nerves, explaining why the technique was unsuccessful.
A prospective, randomized, controlled trial at the authors' institution demonstrated a threefold difference in visual analogue scale (VAS) pain scores between patients receiving periprostatic block and those not receiving the procedure. VAS scores (10 denoting the worst pain ever experienced and 0 denoting no pain) were 1.4 among men who received a block and 4.5 among men who did not receive local anesthetic (P < .0001). Of patients who did not receive periprostatic block, 28.6% reported VAS scores in the moderate range and 28.6% reported scores in the severe range. Only 1 in 27 patients (3.7%) who received local anesthetic reported moderate pain, and none reported severe pain. These findings are consistent with most other reports, with VAS scores being between 4 and 5 among patients not receiving prostatic block in nearly all studies. 
No major complications have been reported with periprostatic block. Injection into the area of the periprostatic nerves could complicate nerve sparing during radical retropubic prostatectomy, but this result has not been observed in the only two published series to address the question or in the more than 650 patients who underwent surgery after periprostatic block at the authors' institution.
The two additional injections through the rectal mucosa could increase the risk of infection or bleeding. However, the authors have not encountered this complication, nor has increased risk been demonstrated in multiple reports. A single report showed an increase in bacteriuria with periprostatic block (including clinical infection in 2 patients), but it also showed less rectal bleeding in the patients who received periprostatic block. The report attributed the increased bacteriuria to the additional 2 punctures through the rectal mucosa and attributed the decreased rectal bleeding to the decreased discomfort of biopsy.  Multiple other reports have shown no increase in bleeding or pain, which is consistent with the findings in over 3000 biopsies at the authors' institution.
A prospective study of 200 patients in Turkey reported no major complications and only minor complications with periprostatic block. The most common finding was pain due to puncture with the needle used for local anesthesia (27%). Other complications recorded included the need for repeated injections during the biopsy procedure (4.5%), symptoms associated with systemic lidocaine toxicity (2%), urinary incontinence (1.5%), and degradation of the image resolution due to anesthetic injection (1%). Increased vascularization within the periprostatic region was uncommon (2%) at 2-week follow-up examination. 
Periprostatic Block: Apical and Multiple Injection Techniques
Soloway and Obek (2000) described the ultrasonic wheal as the visualization of anesthetic into the area of the periprostatic nerve bundle and suggested that 3 separate injections on each side ensured adequate anesthesia. The optimal site of injection is a matter of debate, but the authors have observed that the site of injection is essentially meaningless. The ultrasonic wheal indicates complete nerve blockade whenever the entire nerve bundle adjacent to the prostate is bathed in injectate, regardless of where the injection is performed, as long as the injectate dissects along the course of the nerve.
The vast majority of reports describing successful periprostatic block have involved injection at the base of the prostate. Some authors have described injection variations, such as injection at the apex on either side, direct injection into the prostate, or a single injection of anesthetic into the midline at the level of the apex. The observation of the authors from performing all of these injection variations is that pain relief is reliable and equally effective regardless of the location or number of injections if the agent dissects along the course of both periprostatic nerves.
Achieving reliable and effective pain relief is more difficult with a single injection in the apical midline, but the agent still dissects to the necessary location bilaterally in most cases. Similarly, injection on one side, either in the Mount Everest basilar location or at the level of the lateral apex, leads to dissection of agent to the contralateral nerve bundle in approximately one half of cases.
Based on these observations, the authors believe that the location and the number of injections are of minimal consequence as long as the anesthetic agent is visualized dissecting to the proper location bilaterally. The basilar Mount Everest location offers the largest and easiest-to-define location and therefore remains the authors' preferred technique.
Attempts to inject at the level of the lateral apex or directly into the apex have been based on the observation that apical biopsy is more painful than biopsy of the other areas of the gland. When the authors query attendees at continuing medical education (CME) courses, this observation is confirmed by essentially all urologists. However, the reason for this increased pain in the apex was not understood until 2003, when Jones and Zippe reported that this pain appeared to be related to stimulation of anal pain fibers, not the apex itself.  By performing the rectal sensation test (see below), the apical pain fibers may be bypassed to achieve a painless apical biopsy.
Apical biopsy is crucial because of the predominance of cancers in this location, especially in the anterior portion of the apex. This area is named the anterior horn because of its beaked appearance as it wraps around the transition zone. Studies by Meng et al and others indicate that the anterior horn is the most likely site of cancer that has been missed during a previous biopsy with a false-negative result.  The authors believe that this missed diagnosis is the result of two factors: (1) the anterior horn is difficult to reach, especially with side-fire probes because of their tangential needle tract, and (2) the general perception by urologists is that biopsy of the apex is more painful than biopsy of other areas of the prostate, so urologists may tend to avoid the area in exchange for improved patient tolerance.
Based on anatomic study in collaboration with colorectal surgery colleagues, the authors have determined that the pain associated with apical biopsy is not prostatic pain; rather, the pain originates from anal pain fibers below the dentate line of the rectum, which approximately corresponds to the superior limit of the anal sensory pain fibers. As this area is often near the level of the prostatic apex, a needle often traverses such areas, resulting in significant anal rather than prostatic pain.
The dentate line is identified with the rectal sensation test (see the image below). During this test, the needle is lightly applied against mucosa. It is immediately and strikingly obvious, upon even light touch, if anal pain fibers are present at this level. If the patient answers affirmatively that he feels sharpness, the needle is repositioned 1-2 mm higher until an insensate area is reached (see the second image below). In most cases, the patient does not need to state such perception, as the pain is enough to elicit movement with even a light touch of the needle.
When the needle is advanced cranially above the dentate line, the trajectory is often toward the mid gland, precluding adequate apical biopsy. This needle trajectory is especially problematic because of the need to collect biopsy samples from the anterior horn or peripheral zone tissue.
Angling the probe handle craniodorsally, as shown below, allows the needle to pull rectal mucosa caudally. Painless apical biopsy may then be performed, bypassing the sensory fibers below the dentate line. This action must be performed carefully to avoid dragging the needle against hemorrhoidal vessels in the rectum, which could lead to excessive bleeding. Using the needle tip as the fulcrum, instead of dragging, allows for safe and painless apical biopsy.
VAS pain scores for apical biopsy in patients who have already undergone periprostatic block show improvement over nonblock, from a score of 2.28 to a score of 1.25. 
The implications of these anatomic observations are obvious for periprostatic block at the level of the apex (see the image below). A prospective evaluation at the Cleveland Clinic has found that apical injection appears to be slightly more painful; however, in preliminary data (< 60 patients), the difference has not achieved statistical significance (Jones, 2006, unpublished data).
Recently, a randomized study demonstrated equivalent level of pain control with apical lidocaine block using only 5 mL of injectable lidocaine when compared to two injections of 5 mL lidocaine injected at either base.  This same group also randomized patients to receive an additional intraprostatic dose of injectable lidocaine, and they showed a statistically significant improvement in visual analog pain scales.  At this time, the authors recommend either of these techniques as an adjunct to injection at the prostate base as described.
The authors believe that the demonstration of the efficacy of periprostatic block for prostate biopsy in almost 50 publications clearly has placed this procedure as the standard of care. Patients should expect this level of concern for their comfort and well-being. Further efforts to improve the pain control for probe placement are particularly pertinent, because, to date, no other procedure has been shown to be superior to this maneuver.