U.S. patent number RE42,016 [Application Number 12/572,047] was granted by the patent office on 2010-12-28 for apparatus and method for the treatment of benign prostatic hyperplasia.
This patent grant is currently assigned to AngioDynamics, Inc.. Invention is credited to Victor I. Chornenky, Ali Jaafar.
United States Patent |
RE42,016 |
Chornenky , et al. |
December 28, 2010 |
Apparatus and method for the treatment of benign prostatic
hyperplasia
Abstract
An apparatus and method for treatment of benign prostatic
hyperplasia is disclosed wherein the apparatus includes an
applicator having a probe having proximal and distal probe sections
wherein the proximal and distal probe sections each define an axis
and wherein the axes are not collinear.
Inventors: |
Chornenky; Victor I.
(Minnetonka, MN), Jaafar; Ali (Eden Prairie, MN) |
Assignee: |
AngioDynamics, Inc. (Latham,
NY)
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Family
ID: |
31996683 |
Appl.
No.: |
12/572,047 |
Filed: |
October 1, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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10217749 |
Aug 13, 2002 |
6994706 |
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60412705 |
Sep 23, 2002 |
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60325994 |
Oct 1, 2001 |
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60311792 |
Aug 13, 2001 |
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Reissue of: |
10668775 |
Sep 23, 2003 |
07130697 |
Oct 31, 2006 |
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Current U.S.
Class: |
607/101; 606/41;
607/116 |
Current CPC
Class: |
A61N
1/325 (20130101); A61B 2018/00547 (20130101); A61B
2017/00274 (20130101); A61B 18/1485 (20130101); A61B
18/1477 (20130101); A61B 2018/1425 (20130101) |
Current International
Class: |
A61F
2/00 (20060101); A61B 18/18 (20060101) |
Field of
Search: |
;606/27-31,41,47-50
;607/101,102,115,116,143 ;604/22 |
References Cited
[Referenced By]
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863111 |
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Jan 1953 |
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4000893 |
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Jul 1991 |
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0378132 |
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Jul 1990 |
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EP |
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0935482 |
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May 2005 |
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EP |
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9639531 |
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Dec 1996 |
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WO |
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0020554 |
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Apr 2000 |
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0181533 |
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2004037341 |
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WO |
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|
Primary Examiner: Peffley; Michael
Attorney, Agent or Firm: Ahn; Harry K. Abelman Frayne &
Schwab
Parent Case Text
.Iadd.CROSS-REFERENCE TO RELATED APPLICATIONS .Iaddend.
The present application claims priority to U.S. Provisional
Application No. 60/412,705 entitled "Apparatus and method for
treatment of benign prostatic hyperplasia by electroporation",
which was filed Sep. 23, 2002. This application is a
continuation-in-part of U.S. patent application Ser. No. 10/217,749
entitled "Apparatus and method for treatment of benign prostatic
hyperplasia by electroporation", which was filed Aug. 13, 2002
(U.S. Patent Application Publication 2003/0060856, published Mar.
27, 2003) now U.S. Pat. No. 6,994,706.Iadd., which claims the
benefit of U.S. Provisional Application Ser. No. 60/325,994 filed
Oct. 1, 2001 and U.S. Provisional Application Ser. No. 60/311,792,
filed Aug. 13, 2001.Iaddend..
Claims
What is claimed is:
1. An apparatus for providing electroporation therapy for benign
prostatic hyperplasia, said apparatus comprising: a urethral
applicator configured for insertion into a urethra, said applicator
including: a substantially hollow probe, said probe portion
including first, second and third probe portions, said first probe
portion being configured for insertion into the penile urethral
segment and said third probe portion being configured for insertion
into the prostatic urethral segment, said first and third probe
portions defining first and second probe portion longitudinal axes,
wherein said axes are not collinear with each other and wherein
said second probe portion lies between said first and third probe
portion; a handle, said handle being attached to said probe; a
plurality of needle electrodes, said electrodes being mounted
within said first probe portion for reciprocal movement into and
out of said first probe portion substantially parallel to the
urethra, said electrodes being provided for connection to an
electric pulse generator; wherein when said applicator is disposed
in operating position, said needle electrodes may be advanced into
benign prostatic hyperplasia tissue for electroporation
therapy.
2. The apparatus of claim 1 wherein said first and second probe
portion longitudinal axes are parallel.
3. The apparatus of claim 1 wherein said first and second probe
portion longitudinal axes are non-parallel.
4. The apparatus of claim 1 wherein said third probe portion is
uninsulated and is provided for electrical connection to a pulse
generator.
5. The apparatus of claim 1 wherein said first probe portion has a
greater cross-sectional area than said third probe portion.
6. The apparatus of claim 1 wherein said needle electrodes are
curved.
7. The apparatus of claim 1 wherein said needle electrodes are
bent.
8. The apparatus of claim 1 and further including a flexible fiber
optic endoscope.
9. The apparatus of claim 1 and further including an electric pulse
generator.
10. The apparatus of claim 9 wherein said third probe portion is
uninsulated and is electrically connected to a said electric pulse
generator.
11. The apparatus of claim 1 wherein said first and third probe
portions are longitudinally offset relative to each other.
12. The apparatus of claim 1 wherein said first and third probe
portions are angularly off-set relative to each other.
13. The apparatus of claim 1 wherein said needle electrodes are
electrically insulated from each other and said applicator.
14. The apparatus of claim 1 wherein said handle includes a lever
engaged with said needle electrodes to enable the operator to
selectively advance and retract said needle electrodes.
15. A method of providing electroporation therapy for benign
prostatic hyperplasia comprising: providing an applicator including
a probe having a proximal probe portion and a distal probe
electrode portion, said portions each defining non-collinear
longitudinal axes, said probe including at least one electrode for
electroporation therapy; inserting the applicator into a patient's
urethra to dispose the distal probe portion in the prostatic
urethral segment and the proximal probe portion in the penile
urethral segment and to displace the patient's prostate gland
sideways relative to the proximal probe portion; advancing at least
a first electrode into the benign prostatic hyperplasia tissue; and
applying electric pulses to the distal probe electrode portion and
the at least first electrode to generate electroporating electric
fields.
16. The method of claim 15 and further including: retracting the at
least first electrode following the completion of electroporation
therapy at a first site rotating the probe a preselected amount;
advancing the at least first electrode into the benign prostatic
hyperplasia tissue at a new location in the tissue; and applying
electric pulses to the distal probe electrode portion and the at
least first electrode to generate electroporating electric fields.
Description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to methods and apparatus
for the electroporation of tissues and more specifically to such
methods and apparatus for the treatment of benign prostatic
hyperplasia.
2. Description of the Related Art
Though greater detail will follow in the discussion below,
succinctly stated, the present invention provides apparatus and
methods of providing treatment for the undesirable proliferation of
cells in the prostate by killing the cells with electric field
pulses of selected duration and strength to take advantage of a
cellular event known as "electroporation."
Electroporation
The biophysical phenomenon known as electroporation refers to the
use of electric field pulses to induce microscopic
pores--"electropores"--in the lipid cell membranes. Depending on
the parameters of the electric pulses, an electroporated cell can
survive the pulsing or die. The cause of death of an electroporated
cell is believed to be a chemical imbalance in the cell, resulting
from the fluid communication with the extra-cellular environment
through the pores. For a given cell size, geometry, and
orientation, the number of electropores--and their size created in
the cell by the applied electric field pulses depends on both the
amplitude E of the electric field pulses and the duration t of the
pulses. That is, for a given pulse duration t, no pores will be
induced in the cell until the amplitude E reaches a certain lower
limit. This limit is different for different cells, particularly,
for cells of different sizes. The smaller the size of a cell, the
higher the electric field required to induce pores and thus the
higher the lower limit is. Above the lower amplitude E limit the
number of pores and their effective diameter increases
proportionally with both increasing field amplitude E and pulse
duration t. Electroporation is observed for pulse durations in the
range from tens of microseconds to hundreds of milliseconds.
Until the upper limit of electroporation is achieved, an
electroporated cell can survive the pulsing and restore its
viability thereafter. Above the upper limit the pore diameters and
number of induced pores become too large for a cell to survive. The
irreversibly chemically imbalanced cell cannot repair itself by any
spontaneous or biological process and dies. To kill a cell a
potential in the range of 2 to 4 V should be applied along the
cell. The cell killing by electroporation is a probabilistic
process. That is, increasing the number of applied pulses of
duration t leads to an increased probability of cell killing, a
probability increase that is approximately equal to the percentage
increase in the total time duration of the applied electric
pulses.
The survivability of electroporated cells depends significantly on
their temperature. At higher temperature cells are more vulnerable
to cell death by electroporation. Thus, the amplitude and duration
of the electric pulses required for cell killing are lower. It is
believed that this observation is explained by two underlying
phenomena: at higher temperatures cells are less stable
biochemically because of more intense metabolic activity; and,
secondly, at elevated temperatures the strength of lipid membranes
decreases, which facilitates creating larger pores or irreversible
rupture of the cell membrane. At lower temperatures (about 10 to
about 20 degrees Celsius) cells are more resistant to
electroporation and can survive two to three times higher voltages
than they can at body temperature.
The Prostate Gland and Benign Prostatic Hyperplasia
The prostate gland forms part of the male reproductive system. The
prostate gland is located between the bladder and the rectum and
wraps around the urethra, the tube that carries urine out from the
bladder through the penis. The gland consists a dense fibrous
capsule enclosing several lobes or regions. The prostate gland is
generally composed of smooth muscles and glandular epithelial
tissue. The glandular epithelial tissue produces prostatic fluid.
The smooth muscles contract during sexual climax and squeeze the
prostatic fluid into the urethra as the sperm passes through the
ejaculatory ducts and urethra. Prostatic fluid secreted by the
prostate gland provides nutrition for ejaculated spermatozoids
increasing their mobility and improves the spermatozoids chances
for survival after ejaculation by making the environment in the
vaginal canal less acidic.
Anatomically, the prostate gland is usually described as including
three glandular zones: the central, peripheral and transitional
zones. The transitional zone is located right behind the place
where the seminal vesicles merge with the urethra. This
transitional zone tends to be predisposed to benign enlargement in
later life.
The prostate reaches its normal size and weight (about 20 grams)
soon after puberty. The size and weight of the prostate typically
remain stable until the individual reaches his mid-forties. At this
age, the prostate gland--typically in the transitional zone--begins
to enlarge through a process of excessive cell proliferation known
as benign prostatic hyperplasia (BPH). This overgrowth can occur in
both smooth muscle and glandular epithelial tissues and has been
attributed to a number of different causes, including hormones and
growth factors as well as generally to the aging process.
Benign prostate hyperplasia can cause distressing urination
symptoms. As the disease progresses the dense capsule surrounding
the enlarging prostate prevents it from further expansion outward
and forces the prostate to press against the urethra, partially
obstructing the urine flow. The tension in the smooth muscles of
the prostate also increases which causes further compression of the
urethra and reduction of the urine flow. Some symptoms of BPH stem
from the gradual loss of bladder function leading to an incomplete
emptying of the bladder. The symptoms can include straining to
urinate, a weak or intermittent stream, an increased frequency of
urination, pain during urination, and incontinence--the involuntary
loss of urine following an uncontrollable sense of urgency. These
symptoms alone can negatively affect the quality of life of
affected men. Left untreated, BPH can cause even more severe
complications, such as urinary tract infection, acute urinary
retention, and uremia.
Before age 40, only 10% of men have benign prostatic hyperplasia;
but by age 80, about 80% have signs of this condition. Benign
prostatic hyperplasia is the most common non-cancerous form of cell
growth in men. About 14 million men in US have BPH, and about
375,000 new patients are diagnosed every year.
For many years, researchers have tried to find medications to
shrink the prostate or at least stop its growth. Between 1992 and
1997, the FDA approved four drugs for treatment of BPH:
finasteride, terazosin, tamsulosin, and doxazosin.
Finasteride inhibits production of hormone DHT. DHT is one of the
hormones that have been found to be involved in prostate
enlargement. Treatment with Finasteride has been shown to shrink
the prostate in some men.
Terazosin, doxazosin, and tamsulosin belong to the class of drugs
known as alpha-blockers. Alpha-blockers act by relaxing the smooth
muscle of the prostate and bladder to improve urine flow and reduce
bladder outlet obstruction. In men with severe symptoms, though,
these medications are palliative only. They can delay but not
prevent the eventual need for surgery.
Regardless of the efficacy of any drug treatment, the long term
exposure to xenobiotic compounds may produce additional unwanted
side effects that are not realized until years after treatment.
Accordingly, a need exists for an apparatus and method for the
treatment of BPH that does not require the introduction of
xenobiotic compounds.
For men with the most severe symptoms, surgery is generally
considered to be the best long-term solution. There are several
surgical procedures that have been developed for relieving symptoms
of BPH. Each of these procedures, however, suffers from one or more
of the following deficiencies: high morbidity, long hospital stays,
the use of general anesthesia, significant side effects such as
impotence, and possible complications such as infection and
inflammation.
In recent years, a number of procedures have been introduced that
are less invasive than surgery. One such procedure is transurethral
microwave thermal therapy. In transurethral microwave thermal
therapy, a Foley-type catheter containing a microwave antenna is
placed within the urethra. The microwave antenna is positioned
adjacent to the transitional zone of the prostate, where BPH
occurs, and allows selective heating of the prostate. Maintaining
the temperature of the BPH tissue above 45 degrees C. during about
a one hour session leads to necrosis of the tissues and subsequent
reabsorption of necrotic tissue by the body.
Another recently developed non-invasive technique is transurethral
needle ablation (TUNA). TUNA uses low level radio frequency (RF)
energy to heat the prostate. Using TUNA, two separate needles are
inserted into prostate through the urethra. Several watts of RF
energy is applied to each needle to cause thermal necrosis of the
prostate cells around the needles. Application of this treatment to
several sites of the prostate typically results in sufficient
necrosis to relieve symptoms of the BPH.
While generally successful, the microwave and RF therapies are
relatively long procedures. Also, because of the poor temperature
control of the heated volume, the volume of removed tissue is often
not sufficient for the long term relief of the symptoms and/or the
healthy tissue of the urethra is damaged. A damaged urethra is
capable of restoring itself, but the healing is a long morbid
process accompanied by sloughing of the necrotic tissue into
urethra and excretion of it during urination.
Therefore, a need exists for a minimally invasive therapy for
treatment of BPH that requires shorter treatment times and is less
morbid than existing therapies.
BRIEF DESCRIPTION OF THE INVENTION
The present invention provides apparatus and methods for the
treatment of benign prostate hyperplasia and the alleviation of the
symptoms associated therewith. An apparatus in accord with the
present invention has a probe portion and a handle portion. The
probe portion is preferably entirely or partially hollow.
In an embodiment of the present invention, the probe is a hollow
body having proximal, transitional, and distal probe portions. The
proximal probe portion is a substantially straight, hollow,
elongate tube attached at its proximal end to the handle portion.
The proximal probe section is configured to be received within the
penile section of the urethra and extend to the urogenital
diaphragm, an anatomical structure separating the distal end of the
penis from the prostate gland. The distal probe portion is a
substantially straight, hollow, elongate tube configured to be
received within the prostatic segment of the urethra. The
transitional probe portion is a curved, hollow, tube extending
between the proximal and distal probe portions to form therewith a
continuous, hollow probe capable of being received by the urethra
and extending from the penile opening to within the prostate.
The hollow probe portion provides access for a plurality of
electrodes and other desirable instrumentation to the prostate
gland. For example, a pair of needle electrodes and an flexible
fiber optic endoscope can be housed within the probe portion. If
desired, separate passages or channels can be provided for the
electrodes and the endoscope. The endoscope will preferably extend
the length of the probe, from the probe proximal end to the probe
distal end. The endoscope may be provided to enable the
visualization of the urethra distally to the probe to enable safe
placement and manipulation of the inventive apparatus during
therapy procedures.
The needle electrodes are slidably disposed within the probe to
enable their extension and retraction relative to the probe and
into and out of the BPH tissue. The aforementioned channels or
passages will facilitate their extension and retraction. In their
retracted position, the distal ends of the needles will be
positioned within and near or at the distal end of the proximal
probe portion. When the probe is properly positioned relative to
the prostate gland, advancing the needles will advance them into
the BPH tissue of the prostate gland. Only the distal needle ends
should be exposed; that is, the proximal portions of the needle
electrodes should be insulated to insulate the needle electrodes
from the probe body as well as each other. The proximal ends of the
needles may be secured to a finger activated lever forming part of
the handle portion. The lever is positioned and adapted to advance
the needles relative to the probe to pierce the urethra and thus
position them in the body of the prostate gland; more specifically,
advancing the needles during a procedure will result in the
placement of the uninsulated needle ends being disposed
substantially within the transition zone where BPH occurs.
The curved probe portion serves to displace the proximal and distal
portions from each other. In turn, this displacement displaces the
prostatic urethral segment and the penile urethral segments from
each other. The electrode needles can thus be advanced
substantially parallel to the longitudinal axis of the proximal
portion, and thus the penile urethral segment, into the prostate
gland. Thus, this displacement facilitates ready and proper
positioning of the needle electrodes into the prostate gland
without the necessity of bending needles about 90 into the prostate
gland and without the associated complicated structures found in
the prior art. This probe geometry enables the needles to be placed
into the prostate gland substantially parallel to the urethra,
which in turn enables the use of fewer treatment positions and
shorter treatments.
Preferably, the entirety of the inventive apparatus, save that
portion of the distal probe portion that will be disposed within
the prostatic urethra, is covered with a insulating biocompatible
material. That uninsulated distal probe portion may serve as a
third, urethral electrode. All of the electrodes will be
electrically insulated from each other and will be electrically
connected to a generator producing the electroporation pulses. The
amplitude and duration of the pulses will be selected to provide
and electric field in the prostatic tissue that exceeds the upper
electroporation limit of the BPH fibromuscular and nerve tissues.
The duration of the pulses may be selected to range from about 10
microseconds to about 500 milliseconds. As stated, the amplitude,
duration, and number of pulses will be preselected to cause
necrosis of the fibromuscular and nerve cells constituting the
benign prostatic hyperplasia tissues.
In another embodiment of the present invention, the entire probe
will be insulated and only the needle electrodes will be utilized
for providing electroporation therapy. In this embodiment, no
electric pulses will be applied to the probe itself. It is
anticipated that this embodiment of the present invention will be
used for cases of moderate enlargement of the prostate gland.
Stated alternatively, according to one aspect of the present
invention, the probe portion may have at least three sections,
wherein the first and third sections take on a substantially
tubular form with differing sizes, each of the first and third
sections defining a substantially longitudinal axis, with the first
and third sections' longitudinal axes lying parallel but not
coaxial, and the second section is a transition section between the
first and third sections. The third section is desirably sized to
be safely, comfortably, and appropriately received within the
prostatic segment of the urethra. The first section is desirably
sized to be safely, comfortably, and appropriately configured to be
received within the urethra and extend from urethral opening
through the penis approximately to the urogenital diaphragm. The
second or transitional section is desirably sized to be safely,
comfortably, and appropriately extend through the urogenital
diaphragm. The probe can be manufactured as integral unit or in
separate sections that are joined using known manufacturing
processes.
In another aspect of the present invention, the first and third
probe sections each define a longitudinal axis, with the two axes
being non-parallel.
In yet another aspect of the present invention, the needle
electrodes may be curved.
In still yet another aspect of the present invention, the needle
electrodes may be bent in one location.
In a method in accord with the present invention, a probe having at
least first and second probe portions, with the first and second
probe portions each defining an axis and the first and second probe
portion axes not being collinear, is inserted into the urethra and
maneuvered until the distal end of the probe lies within the
prostatic urethral segment. The distal or second probe portion
displaces the prostate gland sideways relative to the axis of the
proximal or first probe portion. Needle electrodes electrically
connected to a power source are extended from the first probe
portion and inserted into the BPH tissue of the prostate. Electric
field pulses of selected amplitude and duration are applied to the
BPH tissue. In a preferred embodiment, the electric field is
directed radially and thus along the longer dimension of the
fibromuscular cells forming benign prostate hyperplasia as well as
the nerve cells contained therein.
The present invention, while described below with respect to
electroporation, can also be utilized with radio frequency energies
alone or in conjunction with electroporation.
The present invention, as well as its various features and
advantages, will become evident to those skilled in the art when
the following description of the invention is read in conjunction
with the accompanying drawings as briefly described below and the
appended claims. Throughout the drawings, like numerals refer to
similar or identical parts.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates an embodiment of the present invention in a
partial cross sectional view disposed in an operating position
within a human penis and prostate gland.
FIG. 2 shows a cross-sectional view of the present invention taken
along viewing plane 2--2 of FIG. 1.
FIG. 3 shows a cross-sectional view of the present invention taken
along viewing plane 3--3 of FIG. 1.
FIG. 4 depicts an alternative embodiment of an apparatus in accord
with the present invention.
FIG. 5 illustrates an alternative embodiment of an apparatus in
accord with the present invention.
FIG. 6 shows an alternative embodiment of an apparatus in accord
with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
Cells are not, generally speaking, spherical bodies. Rather, they
come in a variety of sizes and geometries. For example, for cells
similar to muscle fiber cells the length to width ratio of the cell
can be as great as 20-30 to 1. Nerve cells can have even greater
length to width ratios. Cell vulnerability to electroporation, as
noted earlier, is different for different directions of the applied
electric field. That vulnerability depends on the size of the cell
in the direction of the applied field. Thus, the effect of
electroporation on tissue can be modulated by selecting a field
direction relative to a cell's geometry. Stated otherwise, an
elongated cell can be killed with significantly lower electric
field strength if the field is applied along the cell. If the field
is applied across such a cell, the cell is capable of surviving
much higher amplitudes of the electric field.
The current invention provides relief of the symptoms of BPH by
providing electroporation treatment to the BPH treatment to create
a necrotic zone in the BPH tissue around the urethra. Control of
the volume of the necrotic zone, its shape, and its location
relative to healthy prostate tissue is provided by the present
invention, including a system of electrodes that generate an
electric field in the area of benign enlargement of the prostate
gland. Application of multiple pulses of the electric field having
the appropriate voltage and duration leads to necrosis of the
prostatic tissue around the urethra.
Anatomically, the predominant direction of fibers in the
fibro-muscular glandular tissue of BPH is radial to the urethra. In
the present invention, the preferred direction of the applied
electric field is also radial to the urethra, coinciding with the
predominant direction of the BPH tissue. Application of the
electroporating pulses along the muscular fibers and nerves that
anatomically follow them selectively kills both types of fibers.
Thus, two intermediate benefits of the present therapy are achieved
with selective application of electroporation pulses to BPH tissue.
First, a significant volume of necrotic BPH tissue around the
urethra is created by the therapy. Second, the nerves that cause
elevation in tension of the muscle fibers are destroyed.
Subsequently, the necrotic tissue, including both the killed BPH
tissue and nerves, are removed by macrophages. Removal of the
necrotic BPH tissue reduces the total volume of BPH and pressure on
the urethra while removal of the destroyed nerves results in
relaxation of the prostate. Both effects contribute to the
improvement of the urethra and bladder functions after
treatment.
While the aforementioned therapy alleviates the symptoms of BPH,
care must be taken to avoid damaging or destroying other tissue in
the vicinity of the applied electroporation pulses. For example,
sphincters, located on the urethra anterior and posterior to the
prostate gland, consist of smooth muscle cells wrapped
circumferentially around the urethra. These urethral sphincters
control shutting down the flow of urine from the bladder and should
be preserved during a therapy treatment. An electroporation field
applied radially to the prostate--that is, coincident with the
elongate fibromuscular and nerve cells of the BPH--results in the
field being transverse to the sphincter muscle cells, thus making
them relatively resistant to the electroporation pulsing. Thus, by
selectively directing the electric field, damage to these muscles,
whose health and function are important to quality of life for
affected individuals, can be reduced or avoided. Nevertheless, to
reduce the potential of damage to the sphincter muscles further,
the electrodes disposed within the urethra during therapy should
not be positioned too closely to them. Additionally, the amplitude
of the electric field during treatment applied to the urethra area
should be selected not to exceed the upper electroporation limit of
the sphincter muscles in the transverse direction.
The foregoing therapeutic benefits are obtained by providing
electroporation treatment to BPH by apparatus and methods in accord
with the present invention.
A BPH therapy applicator and methods of providing BPT treatment in
accord with the present invention are described below with
reference to FIGS. 1-3. Referring specifically to FIG. 1, this
Figure illustrates a BPH therapy applicator 10 comprising a handle
12 and a probe 14. Probe 14 includes at least first and second, or
proximal and distal sections, 16 and 18, respectively. In the
embodiment shown, probe 14 also includes a third or transitional
section 20. The applicator 10 is shown relative to a penis 22 in
position for the application of an electroporation treatment to a
patient experiencing BPH. Thus, the probe 10 is shown inserted into
the urethra 24 through the urethral opening 26 at the proximal end
of the penis 22. As shown in its operational position, probe
proximal portion 16 is disposed within the penile urethral segment
30, probe distal portion 18 is disposed within the prostatic
urethral segment 32, and probe transitional portion 20 extends
between the proximal and distal probe portions 16 and 18 and is
disposed substantially through the urogenital diaphragm 34.
Probe 14 has a substantially hollow configuration, to provide an
interior passage 40. Passage 40 provides access for a flexible
fiber optic endoscope 42 and at least one needle 44. In the
embodiment shown in FIG. 1, two needles, 44 and 46, are shown. One
or more of the endoscope 42 and needles 44 and 46 may be enclosed
within their own individual channels if desired. The endoscope 42
extends to an eye piece 48 at its proximal end 50. A light source
52, which is connected to the endoscope 42 by a fiber optic cable
54, enables visualization of the urethra during placement and
manipulation of the applicator 10 in operation position and during
a BPH electroporation treatment.
Needles 44 and 46 have insulating sheathes 60 on their surfaces
that electrically separate or isolate them from the handle 12 and
probe 14 as well as each other. Needles 44 and 46 are attached to a
finger-activated lever 62 at their proximal ends in any known,
appropriate manner. As seen in the Figure, lever 62 has been moved
from its non-operational position seen in phantom to an operational
position as indicated by the double-headed arrow 64. Movement of
the lever 62 between the two positions will cause the needles to
extend from their non-operational position to an operational
position as seen in the Figure and to retract into their
non-operational position as desired by the lever operator. Thus,
movement of the lever to the operational position shown will cause
the needles to extend or advance through holes 66 and 68 in the
distal end 70 of the first or proximal probe section 16. The
advancement of the needles 66 and 68 out of the probe 14 causes the
needles to pierce the urethra 24 and the urogenital diaphragm 36
and disposes the uninsulated needle ends 74 and 76 of needles 44
and 46, respectively, which form a pair of electrodes, in the body
of the prostate gland 78. Preferably, both the lengths and the
operating positions of the distal end of the distal end 80 of the
probe 14 and the needle electrodes 44 and 46 are selected to avoid
reaching the bladder 82 to reduce the likelihood of damage thereto
during a procedure. In particular, the sharp tips 84 and 86 of
needles 44 and 46, respectively, should not penetrate the bladder
82.
The entirety of the surface of the applicator 10, save for a small
portion 88 of the distal probe section 18 is covered with an
insulating, biocompatible layer of any known or hereafter
discovered, appropriate material. Uninsulated distal probe section
portion 88 is therefore exposed to the surrounding tissue and can
comprise a third, urethral electrode of the applicator 10.
Electrodes 74, 76, and 88 are electrically insulated from each
other and are connected via an appropriate connector 90 to a
generator 92 that produces high voltage electrical pulses. As noted
previously, the amplitude and duration of the electric pulses
applied between the electrodes will be selected to provide an
electric field in the prostatic tissue exceeding the upper
electroporation limit of the BPH tissue, including the nerve cells
contained therein. The pulse duration may be selected to be within
the range of about 10 microseconds to about 500 milliseconds. The
amplitude and number of applied pulses are selected to cause
necrosis of the BPH tissue, including the nerves and muscle
cells.
It will be observed that the proximal and distal probe sections 16
and 18 define longitudinal axes 96 and 98 respectively. As shown,
axes 96 and 98 are not co-linear. They may, if desired, lie
parallel to each other, however. Proximal section 16 has a larger
cross-sectional area than the distal section 18, which does not
need to carry the needles 44 and 46 therein, thus aiding to
increase patient comfort during a procedure. Probe section 20
transitions between the larger cross-sectional area proximal
section 16 and smaller cross-sectional area section 18.
Additionally, the angled or curved nature of the section 20 serves
to offset the proximal and distal sections 16 and 18, respectively,
from each other. In doing so, the prostate gland 78 is displaced
sideways relative to the axis 96 of the proximal section 16. This
sideways displacement facilitates proper positioning of the needle
electrodes in the BPH tissue.
Referring now specifically to FIG. 2, a cross-section of the
prostate gland 78 is shown taken along viewing plane 2--2 of FIG. 1
with the applicator 10 in its operating position. When electric
pulses are applied between the urethral electrode 88 and needle
electrodes 74 and 79, the electric field generated between the
electrodes, indicated generally by field lines 100, causes necrosis
of the BPH tissue. After an electroporation treatment in one site
of the prostate gland is completed, the needles can be retracted
within probe 14 and the probe can be rotated a selected angle to a
new position for treatment. The needles will be advanced into the
operating position and the electric pulses applied once again. A
plurality of such needle advancements and treatments are indicated
in the Figure by the open circles 102.
Referring now specifically to FIG. 3, a cross-section of the
prostate gland 78 is shown taken along viewing plane 3--3 of FIG. 1
with the applicator 10 in its operating position. As shown, the
proximal probe section 16 preferably has a substantially elliptical
configuration with a ratio of the axes in the range of about 1:3 to
about 1:4. The maximal diameter of the ellipse should generally not
exceed about 12 to about 16 mm and minimal diameter should
generally not be less than about 3 to about 4 mm. The fiber bundle
42 of the endoscope and the tow needles 44 and 46 are positioned in
line along the longer axis of the probe section 16. As seen in the
Figure, needles 44 and 46 are disposed, if desired, within channels
or tubes 104.
FIGS. 4-6 show alternative embodiments of the present invention. In
FIG. 4, probe 110 includes proximal and distal segments 112 and
114, respectively. Segments 112 and 114 each define an axis 116 and
118, respectively. As indicated, axes 116 and 118 do not lie
parallel to each other, but are separated by an angle a lying in
the range of about 10.degree. to about 45.degree.. Also as shown,
the needles 44 and 46 can, if desired, be angularly disposed
relative to each other. As seen in the Figure, needles 44 and 46
diverge by an angle .beta. lying in the range of about 0.degree. to
about 30.degree.. In this embodiment, the proximal segment 112 can
be made smaller, thus increasing patient comfort.
FIG. 5 illustrates an embodiment 130 of the present invention
wherein curved needles 132 and 134 having radii of curvature
R.sub.1 and R.sub.2, respectively, are used rather than the
straight needles 44 and 46 previously illustrated and discussed.
Where such curved needles are utilized, the radius of curvature of
the needles are in the range of about 2 cm to about 5 cm.
FIG. 6 depicts another embodiment of the present invention. In this
embodiment, probe 140 includes needles 142 and 142 that are bent at
one location; as shown, the needles 142 and 144 are bent at the end
of the insulating sheath 60.
Operatively, the probe of the present invention will be introduced
into a patient's urethra under endoscopic guidance until the distal
end is positioned in the prostatic segment of the patient's
urethra. The needle electrodes will then be advanced into the BPH
tissue surrounding the urethra and a plurality of electric pulses
will be applied. The electroporation therapy will terminate when a
significant and stable drop in the electrical resistance of the
treated tissue occurs. The resistance drop indicates a profound
electroporation damage to the fibromuscular cells, which later
leads to their necrosis and dissolution by macrophages. Overall
treatment of one site may take about ten pulses and several seconds
to several tens of seconds in time depending on the repetition rate
of the high voltage pulse generator. After each treatment the
needle electrodes will be withdrawn and repositioned in another
treatment site. Consecutive treatments are performed in light of
patient comfort and safety and until the operator determines that a
sufficient volume of BPH tissue has been treated.
It will be obvious to those skilled in the art that many
modifications may be made within the scope of the present invention
without departing from the spirit of thereof, and the invention
includes all such modifications.
* * * * *