Abstract:
Methods and apparatus for treating benign prostatic hyperplasia rely on imparting a low frequency vibration to the prostate. A treatment catheter is introduced through the urethra, and the vibrating element on the catheter energized within the prostate. The low frequency vibration reduces pressure from the prostate on the urethra, possibly by inducing apoptosis of smooth muscle cells.

Description:
CROSS REFERENCES TO RELATED APPLICATIONS 
     The present application claims the benefit of prior provisional application No. 60/871,897, filed on Dec. 26, 2006, the full disclosure of which is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to medical devices and methods for their use. More particularly, the present invention relates to methods and devices for treating benign prostatic hyperplasia by applying low frequency vibration to prostatic tissue. 
     Benign prostatic hyperplasia (BPH), the most common benign neoplasm in males, is a chronic condition that increases in both incidence and prevalence with age. It is associated with progressive lower urinary tract symptoms and affects nearly three out of four men by the seventh decade of life. Benign prostatic hyperplasia is characterized pathologically by a cellular proliferation of the epithelial and stromal elements within the prostate gland P ( FIG. 1 ). As the prostate enlarges, an encapsulating layer of tissue surrounding it inhibits outward expansion, causing the prostate to press against the urethra U like a clamp and also causing a thickening of the bladder wall. The bladder begins to contract even when it contains small amounts of urine, causing more frequent urination. Eventually, the bladder weakens and loses the ability to empty itself, so some urine always remains in the bladder. The narrowing of the urethra and partial emptying of the bladder cause many of the problems associated with BPH. 
     BPH may be treated with drugs, surgically, or with newly developed minimally invasive techniques. Of particular interest to the present invention, the surgical techniques typically involve resection of tissue in a procedure referred to as transurethral resection of the prostate (TURP). In TURP procedures, a resection blade or tool is introduced through the urethra and employed to resect or core tissue through the urethral wall. While often effective, the procedure is painful, has a relatively long recovery, and frequently has side effects such as incontinence and impotence. More recently, less invasive procedures have been developed. In one, referred to as transurethral microwave thermotherapy (TUMT), a microwave antenna is introduced through the urethra and directs microwave energy to heat the prostate to destroy tissue. The heat, however, presents a substantial risk of injury to the urethral wall, even when measures are taken to provide cooling. A second new procedure, referred to as transurethral needle ablation (TUNA), relies on transurethral introduction of a catheter and advancement of a radiofrequency needle into the prostate. While theoretically exposing the urethral wall to less heat, there is still a risk of injury to the urethra, although fewer side effects are observed. Nonetheless, the recovery time for the injured tissue can still be considerable and the use of the radiofrequency energy presents certain risks to the patient. 
     For these reasons, it would be desirable to provide improved methods and systems for treating benign prostatic hyperplasia (BPH). Such methods and systems should minimize the risks and side effects associated with BPH treatment and preferably have a shortened recovery time. In particular, the risk of incontinence and impotence should be greatly reduced and preferably eliminated entirely. It would be still further desirable if the methods and systems did not rely on necrosing tissue, thus avoiding the inflammatory and other responses initiated by tissue necrosis. The methods and systems should be reliable, low cost, and effective. At least some of these objectives will be met by the inventions described below. 
     2. Description of the Background Art 
     U.S. Pat. No. 5,380,273 describes a low frequency vibrating catheter used to disrupt clot in the vasculature. Patents describing transurethral prostate treatments include U.S. Pat. Nos. 4,813,429; 4,967,765; 5,330,518; 5,419,763; 5,454,782; 5,496,271; 6,123,083; 6,389,313; 6,517,534; 6,746,465; and 7,261,710. 
     BRIEF SUMMARY OF THE INVENTION 
     The present invention provides methods and apparatus for treating benign prostatic hyperplasia (BPH) which overcome at least some of the shortcomings of prior treatment modalities as discussed above. In particular, the methods and devices of the present invention can achieve a size reduction in a prostate with minimum trauma and relatively short recovery times. The present invention relies on applying low frequency mechanical vibration to the prostate using a vibrating treatment element positioned within the urethra. The element is vibrated at a frequency in the range from 20 Hz to 200 Hz, preferably from 30 Hz to 100 Hz, and more preferably from 30 Hz to 60 Hz. The vibration is preferably in a lateral direction, but may also include axial, rotational, and more complex vibrational patterns. The extent of lateral displacement imparted against the inner wall of the urethra may vary, typically being in the range from 2 mm to 5 mm, preferably from 1 mm to 2 mm. The vibration is usually achieved by mechanically energizing a treatment element disposed within the urethra, such as rotating an eccentric weight coupled to the treating element, rotating an asymmetric drive shaft coupled to the treating element, or the like. The mechanical motion may be achieved using a motor disposed on a device located in situ within the urethra or alternatively using a drive shaft disposed axially within a device introduced into the urethra. The motor may be electric, hydraulic, fluidic, or have any one of a variety of other configurations. Alternatively, the mechanical vibration could be achieved using a piezoelectric source mechanically configured to reduce the frequency of vibration. Other driving elements include bi-metallic elements driven by an alternating current, spring elements driven by an oscillating tension member, and the like. 
     While the vibrating elements could be introduced in a variety of ways, they will typically be incorporated on or in a catheter or other device having a shaft configured for insertion into the male urethra from the external opening. The length of the catheter or other advancement shaft will typically be in the range from 10 cm to 60 cm, usually from 20 cm to 40 cm, while the diameter will usually be in the range from 1 mm to 10 mm, usually from 3 mm to 6 mm. 
     The vibrating elements will usually be mounted at or near a balloon which helps transfer vibrational energy from the vibrating element into tissue surrounding the balloon (when inflated). Most commonly, the vibrating element(s) will be on the shaft within the interior of the balloon. In that case, the energy will be transferred through the balloon inflation medium (e.g., saline) into the prostatic tissue. In other embodiments, the vibrating element will be positioned in or on the shaft with a balloon asymmetrically positioned on the shaft to push a surface of the shaft directly against the urethral wall. In still other configurations, the vibrating element may be positioned on an outer surface of a balloon or other expandable structure so that expansion of the structure will engage the vibrating element directly against the urethral wall. 
     The treatment devices of the present invention may further comprise an anchoring element for stabilizing and positioning the device within the urethra during the treatment. For example, an inflatable balloon or other expandable anchor may be provided on the shaft which carries the vibrating treatment element. Typically, the anchor will be disposed distally of the treating element so that it may be deployed within the bladder to stabilize and position the vibrating treatment element within the prostate. In addition to balloons, the anchor could comprise a mallecot structure, a deflectable distal end, or other conventional expansible element which may be expanded within the bladder and pulled back against the bladder wall to position the shaft of the device. 
     Further optionally, the treatment devices may include an injector or other means for delivering a therapeutic substance into the prostate as part of the treatment protocol. Typically, the injector will comprise at least one needle which is laterally advanceable from the device shaft. While, in the illustrated embodiments below, the needle is shown to be disposed distally of the vibrating treatment element, it could also be disposed proximally. The delivery of a therapeutic agent may occur before vibrational treatment, concurrently with vibrational treatment, or subsequent to vibrational treatment. Moreover, it would be possible to move the treating device before or after treatment in order to position or reposition the injector to deliver the substance to different locations. Exemplary therapeutic and analgesic substances which may be delivered include lidocaine, alpha blockers, smooth muscle cell contracting stimulants, and the like. 
     The catheter or other treatment device may optionally be coated with a hydrophilic, hydrophobic, and/or antibiotic material to facilitate insertion of the device through the urethra and/or minimize injury to the urethra. Other substances which may be used to coat the device include anti-inflammatory drugs. 
     Although the precise mechanism of action in the treatments of the present application is not known, it is presently believed that the low frequency vibration induces apoptosis or “programmed cell death” within the smooth muscle cells (SMC&#39;s) which are present within the prostate and largely responsible for hyperplasia. As apoptosis results in less inflammation and trauma, a volumetric reduction in the prostate may be achieved with fewer side effects than are associated with radiofrequency ablation, surgical or minimally invasive excisions, and the like. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates the anatomy of the urethra U, prostate P, and bladder B. 
         FIG. 2  illustrates an exemplary treatment device constructed in accordance with the principles of the present invention. 
         FIG. 3  illustrates a first exemplary vibrational element including a motor and eccentric weight which may be carried within the balloon of the treatment device of  FIG. 2 . 
         FIG. 3A  illustrates a vibrational element similar to that illustrated in  FIG. 3  with an asymmetric balloon oriented to engage the element against a urethral wall. 
         FIG. 4  illustrates a motor and a symmetric drive shaft which may be carried by the treatment device of  FIG. 3 . 
         FIG. 5  illustrates a second exemplary vibrational element including an axial drive shaft and an eccentric weight which may be carried by the treatment device of  FIG. 2 . 
         FIG. 6  illustrates an axial drive shaft having an asymmetric distal end which may be carried by the treatment device of  FIG. 5 . 
         FIG. 7  illustrates a treatment device similar to that shown in  FIG. 2 , but further including a tissue injector which may be deployed from the device. 
         FIG. 8  illustrates a treatment device similar to that shown in  FIG. 2 , but further including a distal anchor member. 
         FIG. 9  illustrates a treatment device similar to that shown in  FIG. 2 , including both an injector and a distal anchor. 
         FIGS. 10A-10C  illustrate use of the treatment device of  FIG. 2  for treating BPH. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     As shown in  FIG. 1 , the prostate P is located near the distal end of the male urethra U adjacent the opening or os into the bladder B. The methods and apparatus of the present invention are intended for introduction through the urethra to place a vibrating element within the prostate P. Optionally, an anchoring element will be positioned within the bladder to stabilize the treatment device while it is being used to apply the desired low frequency vibration. Still further optionally, needles or other injectors may be deployed to deliver drugs and/or analgesics into the prostate as part of the treatment. 
     Referring now to  FIG. 2 , a treatment device  10  constructed in accordance with the principles of the present invention includes a shaft  12  having a distal end  14  and a proximal end  16 . Shaft  12  will typically comprise a flexible polymeric extrusion having at least one axial lumen, usually having two or more axial lumens. The shaft could be reinforced, for example with braids, axial wires, or the like, but typically will not need to be. Suitable extrudable polymers include polyamides (nylons), polyether block amides (PEBAX), high density polyethylenes, and the like. 
     The treatment device  10  further includes a handle  18  attached to the proximal end  16  of the shaft  12 . The handle will typically include a thumb switch or other trigger  20  which permits the user to turn on and off the vibration. Alternatively, a foot switch (not shown) could be used. Optionally, handle  18  may be connected to an external unit  22  (shown in broken line) by a cable or other cord  24  to provide energy, drug delivery, control functions, or the like. 
     A balloon  26  is positioned near the distal end  14  of the shaft  12 , and typically one or more radioopaque markers  28  will be provided adjacent to and/or within the balloon to facilitate fluoroscopic imaging. As shown in  FIGS. 3-6 , a vibrating element will be disposed within the balloon. In particular, as shown in  FIG. 3 , a motor  32  may be positioned within the distal end of the shaft and connected to an eccentric weight  34 . The motor will rotate the eccentric weight about a central axis, as illustrated by arrow  36 , causing lateral vibration of the distal end of the shaft. The exact frequency and displacement of the vibration can be controlled by appropriate choice of the speed of motor and mass of the weight. The shaft  12  of the device shown in  FIG. 3  will have at least two lumens. A first lumen  38  is provided for inflating the balloon  26  and a second lumen  40  is provided for routing wires or other conductors  42  needed to power the motor  32 . The motor  32  of  FIG. 3  could be connected to other elements for imparting the desired vibration, including an asymmetric drive shaft  44 , as shown in  FIG. 4 . 
     In  FIG. 3A , a vibrating element similar to that illustrated in  FIG. 3  is shown mounted adjacent to an asymmetrically positioned balloon  26 A. The balloon  26 A is mounted to inflate on one side of the shaft  12  only, as shown in broken line. In that way, the opposite surface of the shaft may be engaged directly against the urethral wall to selectively direct the vibrational energy. 
     An alternative vibrating element structure is illustrated in  FIG. 5 . In  FIG. 5 , the shaft  12  has an axial drive shaft  50  which extends from the proximal end of the shaft to the distal end, typically through a drive shaft lumen  52 . A motor may be provided within the handle  18  ( FIG. 2 ) in order to rotate the shaft shown by arrow  54  An eccentric weight  56  may be attached to the distal end of the shaft in order to transmit vibrations to the shaft within the balloon  26 . A separate balloon inflation lumen  58  will be provided. As an alternative to the eccentric weight  56 , the drive shaft  50  may have an asymmetric structure  60  at its distal end, as shown in  FIG. 6 . 
     The treatment devices of the present invention may be combined with other features to enhance their utility and effectiveness. For example, as shown in  FIG. 7 , a laterally deployable injector  70  may be provided within a separate lumen within the shaft  12 . Typically, a distal end  72  of the needle (shown in broken line) will be adapted to deploy laterally through a port  74  in the shaft so that it may be directed into the prostatic tissue from the urethra. The other elements of the treatment device may remain as described previously. 
     As shown in  FIG. 8 , a stabilizing balloon  76 , or other expandable element such as a malecot, may be provided distally of the treatment balloon  26 . The anchor  76  will be positioned to be expanded within the bladder to provide both forced stabilization and positioning of the treatment balloon  26  within the prostate. As shown in  FIG. 9 , both the injector  70  and the stabilizing element  76  may be combined on a single shaft  12 . 
     Referring now to  FIGS. 10A-10C , use of the device  10  for treating a prostate P will be described. As shown in  FIG. 9A , the prostate P surrounds a distal end of the urethra U adjacent the bladder B. The shaft  12  may be advanced through the urethra U so that the treatment balloon  26  is disposed within the prostate P adjacent the bladder B, as shown in  FIG. 10B . Optionally, a stabilizing element may be advanced within the bladder and inflated or expanded to permit pullback of the shaft  12  to enhance positioning and stability (not shown). Once proper positioning of the shaft  12  and treatment balloon  26  is confirmed using a cystoscope or fluoroscopically, the treatment balloon  26  may be expanded, as shown in  FIG. 10C . The balloon thus engages the inner wall of the urethra and expands against the prostate P. The vibrating element is then energized, causing the balloon to vibrate, usually in a lateral direction as shown by the broken line in  FIG. 10C . The treatment will then be performed at the frequencies and displacements described above, typically for a time in the range from 30 minutes to 60 minutes. Treatment may be performed more than once in any session, and may be repeated as often as the hyperplasia recurs. 
     While the above is a complete description of the preferred embodiments of the invention, various alternatives, modifications, and equivalents may be used. Therefore, the above description should not be taken as limiting the scope of the invention which is defined by the appended claims.