U.S. patent application number 13/019911 was filed with the patent office on 2011-08-25 for methods and systems for restoring patency.
This patent application is currently assigned to EMcision Limited. Invention is credited to Nagy Habib.
Application Number | 20110208181 13/019911 |
Document ID | / |
Family ID | 44477134 |
Filed Date | 2011-08-25 |
United States Patent
Application |
20110208181 |
Kind Code |
A1 |
Habib; Nagy |
August 25, 2011 |
METHODS AND SYSTEMS FOR RESTORING PATENCY
Abstract
A method for maintaining patency in a duct or hollow vessel
located within the body of a patient is described wherein the duct
includes one or more obstructions. The method comprises the steps
of introducing a device into the duct, the device comprising a
catheter having a distal and a proximal end, wherein the distal end
includes a distal tip portion and wherein the distal tip portion
comprises at least one energy delivery member; locating the device
within the duct at a position proximal to the obstruction;
delivering energy to the duct and any surrounding tissue via the at
least one energy delivery member for a specified time period, so
that the obstruction is removed from the duct; and withdrawing the
device from the duct. It is optional to subsequently place a device
such as a stent at the therapy site in order to further maintain
long term patency of the duct. It is also optional to apply a
dilation force to the duct or hollow vessel after the energy
delivery phase. Systems are also described for performing the
methods of the disclosure.
Inventors: |
Habib; Nagy; (London,
GB) |
Assignee: |
EMcision Limited
Hitchin
GB
|
Family ID: |
44477134 |
Appl. No.: |
13/019911 |
Filed: |
February 2, 2011 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61301994 |
Feb 5, 2010 |
|
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61302434 |
Feb 8, 2010 |
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Current U.S.
Class: |
606/33 ;
606/128 |
Current CPC
Class: |
A61B 2017/00084
20130101; A61B 2017/22001 20130101; A61B 18/1492 20130101; A61B
2018/00702 20130101; A61B 2018/00875 20130101; A61B 2017/22038
20130101; A61B 2018/00422 20130101 |
Class at
Publication: |
606/33 ;
606/128 |
International
Class: |
A61B 17/22 20060101
A61B017/22; A61B 18/18 20060101 A61B018/18 |
Claims
1. A method for maintaining patency in a duct located within the
body of a patient, wherein the duct includes one or more
obstructions, the method comprising the steps of: (a) introducing a
device into the duct, the device comprising a catheter having a
distal and a proximal end, wherein the distal end includes a distal
tip portion and wherein the distal tip portion comprises at least
one energy delivery member; (b) locating the device within the duct
at a position proximal to the obstruction; (c) delivering energy to
the duct and any surrounding tissue via the at least one energy
delivery member for a specified time period, so that the
obstruction is removed from the duct; and (d) withdrawing the
device from the duct.
2. The method of claim 1, wherein the distal tip portion of the
device comprises a plurality of energy delivery members.
3. The method of claim 1, wherein the energy delivery member
comprises a radiofrequency (RF) electrode.
4. The method of claim 1, wherein the energy delivery member
comprises at least two RF electrodes arranged in a bipolar
configuration.
5. The method of claim 4, wherein the at least two RF electrodes
are spaced at least about 1 mm and at most about 15 mm apart.
6. The method of claim 4, wherein the at least two RF electrodes
are spaced no more than about 8 mm apart.
7. The method of claim 1, wherein the device further comprises a
sensor for measuring impedance in the tissue whilst energy is
delivered to the duct and surrounding tissues in step (c).
8. The method of claim 1, wherein the device further comprises a
temperature sensor within the distal tip portion.
9. The method of claim 1, further comprising the additional step
of: (e) inserting a stent into the duct at the location proximal to
the obstruction where the energy was delivered so as to maintain
patency in the duct.
10. The method of claim 1, wherein the position proximal to the
obstruction in step (e) already comprises a pre-located stent that
has become obstructed subsequent to placement in the duct.
11. The method of claim 1, further comprising the additional step
of: (e) applying a dilation force to the duct so as to maintain
patency.
12. The method of claim 11, wherein the dilation force is applied
via use of a balloon dilation catheter.
13. The method of claim 11, wherein the dilation force is applied
via use of a tethered SEMS catheter.
14. The method of claim 1, wherein the duct is a duct comprised
within the biliary tree.
15. The method of claim 1, wherein the duct is a fallopian
tube.
16. The method of claim 1, wherein the duct is a bronchiole.
17. The method of claim 1, wherein the duct is the oesophagus.
18. The method of claim 1, wherein the duct is part of the urinary
tract.
19. The method of claim 1, wherein the duct is part of the
gastrointestinal tract, including the stomach.
20. The method of claim 1, wherein the obstruction is tumor.
21. The method of claim 1, wherein the obstruction comprises
granulation tissue.
22. The method of claim 1, wherein the obstruction comprises a
thrombosis.
23. The method of claim 1, wherein the obstructions comprises a
stricture.
24. The method of claim 1, wherein the obstruction comprises
varices.
25. The method of claim 1, wherein an energy level of no more than
about 10 Watts is applied in step (c).
26. The method of claim 1, wherein an energy level of no less than
about 1 and no more than about 8 Watts is applied in step (c).
27. The method of claim 1, wherein the specified time period for
delivery of energy is no less than about 10 and no more than about
300 seconds.
28. The method of claim 1, wherein the specified time period for
delivery of energy is no more than about 2 minutes (120
seconds).
29. A method for maintaining the method comprising the steps of:
(a) introducing a first device into the duct, the first device
comprising a catheter having a distal and a proximal end, wherein
the distal end includes a distal tip portion and wherein the distal
tip portion comprises at least one energy delivery member; (b)
locating the first device within the duct at a position proximal to
an obstruction; (c) delivering energy to the duct and any
surrounding tissue via the at least one energy delivery member for
a specified time period, so that the obstruction is removed from
the duct, and then withdrawing the first device from the duct; and
(d) introducing a second device into the duct and locating the
second device at the position proximal to the obstruction, wherein
the second device is configured to apply a dilation force to the
duct so as to maintain patency.
30. The method of claim 29, wherein the second device comprises a
balloon dilation catheter.
31. The method of claim 29, wherein the second device comprises a
stent delivery catheter.
32. A system for restoring at least partial patency of a duct that
has been subject to an occlusion, by increasing the luminal
diameter of the duct, in a patient in need thereof, the system
comprising: (i) a first device that comprises an endoscope, the
endoscope comprising at least one central lumen extending along its
length; (ii) a second device that comprises a catheter, the
catheter having a distal terminus and a region proximal to the
distal terminus defining a distal tip region, the distal tip region
comprising at least one RF electrode; and (iii) a third device that
comprises a stent delivery catheter and a stent that is to be
delivered by the stent delivery catheter; wherein the central lumen
of the first device is configured so as to be of a diameter that is
able to accommodate the second and third devices consecutively.
33. The system of claim 32, wherein the central lumen is a biopsy
channel.
34. The system of claim 32, wherein the second device comprises a
second lumen, and wherein the second lumen is configured in order
that the second device can be mounted on a guide wire.
35. The system of claim 32, wherein the second device comprises at
least two RF electrodes in a bipolar configuration.
36. The system of claim 32, wherein the at least two RF electrodes
are spaced no more than about 8 mm apart.
37. The system of claim 32, wherein the stent is a SEMS.
38. A system for restoring at least partial patency of a duct that
has been subject to an occlusion, by increasing the luminal
diameter of the duct, in a patient in need thereof, the system
comprising: (i) a first device that comprises an endoscope, the
endoscope comprising at least one central lumen extending along its
length; (ii) a second device that comprises a catheter, the
catheter having a distal terminus and a region proximal to the
distal terminus defining a distal tip region, the distal tip region
comprising at least one RF electrode; and (iii) a third device that
comprises a balloon dilation catheter; wherein the central lumen of
the first device is configured so as to be of a diameter that is
able to accommodate the second and third devices consecutively.
39. The system of claim 38, wherein the central lumen is a biopsy
channel.
40. The system of claim 38, wherein the second device comprises a
second lumen, and wherein the second lumen is configured in order
that the second device can be mounted on a guide wire.
41. The system of claim 38, wherein the second device comprises at
least two RF electrodes in a bipolar configuration.
42. The system of claim 38, wherein the at least two RF electrodes
are spaced no more than about 8 mm apart.
Description
RELATED APPLICATION
[0001] This application claims the full Paris Convention benefit of
and priority to U.S. Provisional Patent Application Ser. No.
61/302,434, filed Feb. 8, 2010, and U.S. Provisional Patent
Application Ser. No. 61/301,994, filed Feb. 5, 2010, the contents
of which are incorporated by reference herein in their entirety, as
if fully set forth herein.
FIELD
[0002] The disclosure relates to methods for restoring patency in a
duct or hollow vessel located within the body of a patient.
BACKGROUND
[0003] As many as 90% of patients who present with pancreatic
adenocarcinoma or extrahepatic cholangiocarcinoma will have
surgically unresectable disease, either because of local vascular
involvement or metastatic disease. Life expectancy in patients with
unresectable disease is poor, with a median survival of six to
eight months. Most of these patients will experience biliary
obstruction and jaundice. The priority in the management of such
patients is to effectively and durably relieve the jaundice. By
relieving jaundice the patient feels better, quality of life is
improved and if appropriate facilitates chemotherapy. Malignant
biliary obstruction is relieved either by deploying a stent through
endoscopic retrograde cholangiography (ERC) or percutaneous
transhepatic cholangiography (PTC). In most cases a self-expanding
mesh metal stent (SEMS) is used which has a longer patency than a
plastic stent.
[0004] Despite using SEMS patients often continue to have problems
with stent occlusion produced from tumor ingrowth. From a technical
perspective this can be a difficult problem to treat requiring in
hospital management and repeated biliary interventions.
[0005] Deployment of radiofrequency (RF) energy via a catheter or
endoscope has been used in the past in order to destroy or ablate
tissue. U.S. Pat. No. 6,066,139 describes an apparatus comprising a
bipolar RF catheter for use in creating thermal lesions for the
purpose of sealing or ligating vessels such as fallopian tubes or
embolizing blood vessels. The apparatus described in U.S. Pat. No.
6,066,139 administers RF energy to heat surrounding tissue to a
temperature of between 95.degree. C. and 105.degree. C.
(203.degree. F. to 221.degree. F.) in order to cause necrosis of
the tissue and collapse of the duct or vessel. RF energy has also
been applied for the purpose of bile duct ablation as described in
WO-03/053,267. Hence, whilst the use of RF energy to ablate or
induce closure of vessels within the body is known, use of
controlled energy delivery to maintain or restore patency in an
already obstructed vessel or duct has not been considered
previously.
[0006] There is a need to provide additional methods for treating
problems such as stent occlusion caused by tumor ingrowth, and
restoration of patency in ducts or vessels obstructed by tissue or
other material.
DESCRIPTION
[0007] To improve the patency of obstructed ducts, such as by
malignant tumor obstruction, the present inventors have developed a
radiofrequency (RF) catheter that can be inserted over a guidewire
with the aim that controlled application of RF energy can be used
to ablate a luminal tumor or other occlusion and optionally prior
to insertion of a stent, such as a SEMS. The clinical use of RF has
an established role in the ablation of cancers in solid organs such
as the liver. However, the use of RF to maintain patency in ducts
such as those of the biliary system has not been disclosed
before.
[0008] Accordingly, in a first aspect the disclosure provides a
method for maintaining patency in a duct located within the body of
a patient, wherein the duct includes one or more obstructions, the
method comprising the steps of:
[0009] (a) introducing a device into the duct, the device
comprising a catheter having a distal and a proximal end, wherein
the distal end includes a distal tip portion and wherein the distal
tip portion comprises at least one energy delivery member;
[0010] (b) locating the device within the duct at a position
proximal to the obstruction;
[0011] (c) delivering energy to the duct and any surrounding tissue
via the at least one energy delivery member for a specified time
period, so that patency is restored to the duct; and
[0012] (d) withdrawing the device from the duct.
[0013] In a specific embodiment, the method of the disclosure may
further comprise the additional step of:
[0014] (e) inserting a stent into the duct at the location proximal
to the obstruction where the energy was delivered so as to maintain
patency in the duct.
[0015] Suitable stents may be selected from SEMS or plastic
stents.
[0016] In some exemplary implementations there may be an additional
step of:
[0017] (e) applying a dilation force to the duct so as to maintain
patency.
[0018] In such exemplary implementations the dilation force may be
applied by insertion of a second device into the duct that
comprises one or more expandable members that are able to apply
radial force on the walls of the duct. Suitably the second device
is a balloon dilation catheter. Optionally the device comprises an
expandable mesh structure such as a tethered self expanding
stent.
[0019] In some exemplary implementations the method of the
disclosure can be used where the position proximal to the
obstruction already comprises a pre-located stent that has become
obstructed subsequent to prior placement in the duct.
In some exemplary implementations a system for restoring full or
partial patency by increasing the luminal diameter of a duct that
has been subject to full or partial occlusion, in a patient in need
thereof. The system comprises: a first device that comprises an
endoscope, the endoscope comprising at least one central lumen
extending along its length; a second device that comprises a
catheter, the catheter having a distal terminus and a region
proximal to the distal terminus defining a distal tip region, the
distal tip region comprising at least one or more RF electrodes;
and a third device that comprises a SEMS delivery catheter;
[0020] wherein the central lumen of the first device is configured
so as to be of a diameter that is able to accommodate the second
and third devices consecutively. Typically the central lumen will
be in the form of a biopsy channel. In specific embodiments of the
invention the second device may comprise a central lumen also, in
order that it can be placed over a prelocated guidewire.
[0021] Some exemplary implementations of the disclosure relate to
removal or displacement of obstructions from ducts within the
pancreatic and biliary networks. These examples are not intended to
be a limitation on the use.
DRAWINGS
[0022] The above-mentioned features and objects of the present
disclosure will become more apparent with reference to the
following description taken in conjunction with the accompanying
drawings wherein like reference numerals denote like elements and
in which:
[0023] FIG. 1 shows a close up photograph of the distal end of a
bipolar RF device suitable for use in the present disclosure
showing two ring electrodes (A and B) which are spaced 8 mm apart
and the most distal electrode (marked A) is 5 mm from the distal
terminus of the catheter. The line C shows the approximate length
of the RF ablation zone (around 25 mm) generated in a cylindrical
region coaxial to the electrodes.
[0024] FIG. 2 shows a microscopy image of a Haematoxylin and Eosin
stained resected common bile duct, demonstrating a mild thermal
injury. In the common bile duct there is erosion with patchy
denudation of the epithelium. Underlying glands show some
dilatation and focal inflammation but no necrosis.
[0025] FIG. 3 shows a microscopy image of a Haematoxylin and Eosin
stained of resected common bile duct, demonstrating a moderate
thermal injury. Complete burn with no residual epithelium.
Subepithelial cleft-like spaces filled with blood cells.
[0026] FIG. 4 shows a photograph of a laparotomy in which a heating
effect on the outer surface of tissue surrounding the bile duct and
extending into pancreas was observed. Tip of forceps pointing to
area of coagulative necroses outside target area. The RF device had
been activated at 20 Watts for 1 minute.
[0027] FIG. 5 shows a microscopy image of a Haematoxylin and Eosin
stained resected common bile duct, demonstrating severe thermal
injury. Significant thermal changes with extensive coagulative
necrosis of the wall are found.
[0028] FIG. 6 shows a diagram of the biliary tree in humans
comprising the various constituent ducts and also the surrounding
organs: (1) liver, (2) right hepatic duct, (3) left hepatic duct,
(4) common hepatic duct, (5) cystic duct, (6) common bile duct, (7)
gall bladder, (8) sphincter of Oddi, (9) ampulla of Vater, (10)
pancreatic duct, (11) pancreas, and (12) duodenum.
[0029] FIGS. 7(a) to (d) show a series X-ray photographs (via
endoscopic retrograde cholangiopancreatography (ERCP)) of the
endoscopic insertion and administration of RF energy to restore
patency in a blocked bile duct in a mammalian system. (a) the
position of the obstruction in the CBD is shown by the white arrow.
(b) the position of the distal electrode on the RF catheter is
indicated by the white arrow.
FURTHER DESCRIPTION
[0030] Prior to setting forth the invention, a number of
definitions are provided that will assist in the understanding of
the disclosure. All references cited herein are incorporated by
reference in their entirety. Unless otherwise defined, all
technical and scientific terms used herein have the same meaning as
commonly understood by one of ordinary skill in the art to which
this disclosure belongs.
[0031] The term "duct" is used herein to denote a hollow vessel or
channel located within the body of a patient. Typically, ducts may
lead to or from an organ and may be involved in the transport of
endocrine or other secretions within the body. In accordance with
the present disclosure, ducts do not typically include
blood-carrying vessels such as veins, arteries or arterioles, but
may include vessels of the lymphatic system. Ducts that are
suitably treated in accordance with the methods of the present
disclosure may be selected from ducts and channels that comprise
part of the biliary system, including the common bile duct (CBD),
the pancreatic duct, the cystic duct, the right and left hepatic
ducts and the common hepatic duct (see FIG. 6). Other ducts may
include fallopian tubes; channels within the respiratory system,
such as bronchioles; channels within the gastrointestinal tract,
including the oesophagus; and channels that are a part of the
urinary tract, including the ureters and the urethra, including for
the treatment of benign or malignant prostatic disorders. The
method of the disclosure can also be applied in the ventricular
system for relief of fluid build up in conditions such as
hydrocephalus.
[0032] The term "obstruction" is used herein to denote an
accumulation of matter, or tissue that partially or completely
blocks the duct so as to affect normal patency of the duct.
Typically obstructions are caused by a benign or malignant tumor
present in tissue within the duct or in tissue adjacent to the
duct--thereby causing obstruction by means of compression of the
duct. Alternative obstructions can result by an accumulation
granulation tissue (scar tissue) as a result of prior trauma, such
as injury or surgery, or a pathological condition (for example,
endometriosis or infection). Obstructions caused by scar tissue can
sometimes result in a stricture of the duct, thereby leading to a
blockage. A further obstruction my result from formation of a blood
clot (thrombosis) within the duct, possibly following traumatic
injury or acute infection.
[0033] The term "patency" is used herein to denote the level of the
openness (lack of obstruction) of a bodily passage or duct. A fully
patent duct is one that is functioning normally with no significant
obstruction. A semi-occluded duct may be regarded as functionally
patent in spite of partial obstruction, whereas an obstructed duct
would generally be considered to be non-patent. The method of the
present disclosure is suitable for use in situations where
restoration to full or at least partial patency is required in a
duct that is blocked or functionally occluded. Restoration to full
or at least partial patency in ducts such as the common bile duct
is sufficient in many cases to relieve symptoms of jaundice and/or
pancreatitis in patients with hepatic or pancreatic tumors.
[0034] Suitable devices that can be used in the method of the
disclosure are catheters, probes, endoscopes or guidewires that
comprise the ability to provide topical delivery of energy at a
specified location within the body of a patient. The use of
radiofrequency energy is exemplified in the examples set out in
detail below, however it is understood that alternative energy
delivery systems, such as ultrasound, microwave, electrical or
laser energy could be employed in the method of the disclosure. RF
devices that may be used according to the methods of the disclosure
are described in the inventor's co-pending International Patent
applications WO-A-2007/135,431 and WO-A-2008/084,239 the contents
of which are incorporated herein by reference. A specific
implementation of the disclosure utilizes a catheter that comprises
one or more radiofrequency (RF) electrodes at the distal tip. In a
particular embodiment of the disclosure, the energy delivery member
comprises at least two RF electrodes arranged in a bipolar
configuration (see FIG. 1). Typically, the at least two RF
electrodes are spaced no less than about 1 mm and no more than
about 15 mm apart; optionally no less than about 2 mm and no more
than about 12 mm apart; suitably between about 3 mm and about 10 mm
apart. In one embodiment of the disclosure, the at least two RF
electrodes are spaced about 8 mm apart.
[0035] In some exemplary implementations optimal spacing of RF
electrodes allows for the delivery of energy in a substantially
cylindrical region coaxial to the distal tip of the device and
extending between and about the at least two electrodes. An
advantage of this arrangement is that the energy is dissipated over
a larger area, thereby reducing the formation of localized hotspots
(foci) that can lead to excessive thermal damage of surrounding
healthy tissue. In some exemplary implementations the bipolar
electrode arrangement is such that the most distal electrode is not
located at the leading edge (distal terminus) of the device, but
rather about 5 mm behind the distal terminus. This arrangement
helps to prevent collapse of the duct during the thermal ablation
phase.
[0036] A specific embodiment of the present disclosure provides for
controlled delivery of energy to the site of therapy--i.e. the
location in the duct where a blockage has occurred. Controlled
release of energy is sufficient to induce ablation and remodelling
of tissue or material that is responsible for the obstruction, but
not so much as to induce extreme tissue damage that would result in
collapse of the duct (permanent obstruction) or organ failure. In
one particular embodiment of the disclosure the level of energy
(power) applied to the obstruction via the device is no more than
about 10 Watts (10 W), typically no less than 1 W and up to 8 W,
more suitably around 6 W or 7 W. The total energy applied to the
treatment site will vary from patient to patient, however, in an
example of the disclosure in use the total energy applied in
procedures to restore patency to occluded biliary ducts was no less
than 1200 Joules and up to 3600 Joules in the procedure as a whole.
It will be appreciated that for more minor blockages lower amounts
of total energy will be sufficient to restore patency, whereas for
more acute strictures a greater amount of energy will be
required.
[0037] Energy will be applied at the site of treatment in one or
more discrete time periods of administration. The time period for
administration of energy to the therapy site (proximal to the
obstruction) is usually for no less than about 10 and no more than
about 300 seconds and suitably no less than about 30 and no more
than about 200 seconds. In examples described in more detail below
the specified time of energy delivery is set at around 2 minutes
(120 seconds). However, it will be understood by the skilled person
that this time may vary depending upon the nature of the
obstruction (thrombus, stricture or tumor), the location of the
duct within the body (particularly with respect to significant
local anatomy) and also the power rating of the device being used
in the method. In some exemplary implementations restoration of
patency to an occluded common bile duct may require several
applications of energy with intervals of rest periods to allow the
ablated tissue to cool so as to avoid unnecessary heating of
surrounding tissues. Rest periods may suitably range from at least
1 second to at most 2 or 3 minutes, although typically a rest
interval might be around one minute in length. In this way removal
of the occluding mass and the corresponding increase in lumenal
diameter is achieved by sequential applications of energy along the
length of a stricture within the compromised duct or vessel.
[0038] To assist with the control of energy delivery, devices used
in the method of the invention may further comprise a sensor for
measuring impedance in the tissue whilst energy is delivered to the
duct and surrounding tissues in the energy delivery step. Observing
the level of electrical impedance in the surrounding tissue is one
way of monitoring the progress of the therapy/heating phase. For
instance, electrical impedance can be monitored during heating and
when a predefined threshold is reached the heating phase is deemed
to have been completed. Likewise, the device can further comprise a
temperature sensor within the distal tip portion.
[0039] In some exemplary implementations described in more detail
below, a method is provided of using endoscopically applied
radiofrequency treatment prior to insertion of a self expanding
metal stent (SEMS) in an un-resectable malignant bile duct
obstruction. At present, the use of SEMS is the standard technique
to ensure continued biliary drainage in patients with life
expectancy beyond 3 months. However, up to 50% of patients with
SEMS will re-present with stent occlusion within the first 6-8
months, this often leads to significant morbidity and mortality as
well as delays in chemotherapy regimes. The present disclosure
allows for restoration of patency through minimally invasive
procedures thereby allowing for amelioration of the symptoms of
bile duct obstruction.
[0040] SEMS are typically open-ended cylinders constructed from a
metal wire mesh, including shape memory alloys such as nitinol and
platinum coated nitinol. The SEMS are designed to resist radial
compression when in the expanded state and conform easily to the
anatomy of the vessel or duct in which they have been deployed. In
this way the SEMS will support the duct and resist collapse
following thermal ablation treatment according to the methods of
the present invention. Exemplary SEMS suitable for use in the
methods and systems of the invention include Zilver.RTM. brand
biliary SEMS (Wilson-Cook Medical, Inc., NC, USA) or Wallstent.RTM.
SEMS (Boston Scientific, Inc., MA, USA).
[0041] In accordance with a specific embodiment of the disclosure a
typical procedure may involve the following steps:
[0042] (1) a suitable endoscope is inserted into or proximate to
the occluded duct; the endoscope will comprise a channel of a size
suitable to accommodate and facilitate deployment of a catheter
that includes a bipolar RF electrode energy delivery module at its
distal tip (see FIG. 7(a));
[0043] (2) the endoscope and/or the catheter will be advanced to a
position within the duct that is proximate to the site of full or
partial obstruction (which may or may not include a pre-located
stent); this may be facilitated by the use of a guidewire as well
as ECRP or other suitable imaging techniques;
[0044] (3) when the catheter tip is located at the correct
position, RF energy is applied at a power level and for one or more
specified time periods to induce ablation of the obstruction but
not widespread necrosis or significant damage of the duct that
would result in permanent occlusion (see FIG. 7(b));
[0045] (4) the catheter can be withdrawn from the treatment site
when patency is established (via X-ray fluoroscopy, for example)
and if necessary applied to one or more additional obstructions
(see FIG. 7(c));
[0046] (5) in an optional additional step, a SEMS is inserted into
the location where therapy has been applied in order to maintain
patency for a longer period of time (see FIG. 7(d)). Further SEMS
may be inserted proximate to the first inserted SEMS in order to
maintain a patent tract of the duct.
[0047] In certain circumstances it may not be clinically necessary
or appropriate to insert a stent, such as a SEMS, into the duct. In
such cases it may, nevertheless, be desirable to apply a radial
expansive force to the duct in order to further assist the effects
thermal ablation. Application of an expansive force to the duct can
be achieved by methods known to the skilled person, and may include
subsequent deployment of a balloon catheter dilator or equivalent,
or use of a tethered expanding stent that is removed from the
vessel immediately following the application of the expansive
force. Suitable devices for administering an expansive force to the
duct under treatment may include use of a wireguided balloon
dilator, such as the CRE.TM. Wireguided Ballon Dilator,
Extractor.TM. RX Retrival Balloon system or Gateway.TM. PTA Balloon
Catheter (Boston Scientific, MA, USA). Typically balloon dilators
will comprise a catheter-type elongated body which further
comprises a one of more extended bladders (or balloons) at the
distal end of the device. The bladders may be inflated by injection
of a fluid (such as saline) into a chamber comprised within the
bladder, thereby exerting a dilatory or radially expansive force on
tissue surrounding the bladder when placed within a vessel or duct.
The dilation radius and force can be controlled by the user of the
device, so as to avoid risk of rupture of the duct or vessel.
[0048] In some exemplary implementations a system for restoring
full or partial patency by increasing the luminal diameter of a
duct that has been subject to full or partial occlusion, in a
patient in need thereof. The system comprises:
[0049] (i) a first device that comprises an endoscope, the
endoscope comprising at least one central lumen extending along its
length;
[0050] (ii) a second device that comprises a catheter, the catheter
having a distal terminus and a region proximal to the distal
terminus defining a distal tip region, the distal tip region
comprising at least one or more RF electrodes; and
[0051] (iii) a third device that comprises a stent delivery
catheter and a stent that is to be delivered by the stent delivery
catheter;
[0052] wherein the central lumen of the first device is configured
so as to be of a diameter that is able to accommodate the second
and third devices consecutively.
[0053] Such systems, or aspects thereof, may comprise a standard
endoscope with optical or ultrasound guidance features, that
further comprises a central lumen or channel--such as a biopsy
channel--that is able to accommodate the second or third devices.
The endoscope is used to locate the site of duct occlusion (e.g.
stricture), at which point an optional standard guide wire can be
inserted into the central lumen and over which the RF catheter is
advanced to a location proximate to the site of the blockage. The
RF catheter is deployed and ablation energy is applied to the
occluded region in accordance with the methods disclosed herein.
Once a satisfactory level of patency is achieved the second device
is removed from the first device and the third device is advanced
to the site of treatment--over the guide wire if one is present--to
allow for deployment of a SEMS. In some cases more than one SEMS
may be required at the treatment site, hence, systems may include a
plurality of third devices.
[0054] It will be appreciated by on of ordinary skill in the art
that the methods and systems of the disclosure are not limited to
use solely in the biliary system and that other ducts or hollow
anatomical structures may be subject to equivalent treatment where
occlusion or other pathological malformation is present. In an
exemplary implemenation the system, or aspects thereof, described
above is utilized in the treatment of gastro-esophageal varices. By
way of non-limiting example, occlusions in the esophagus caused by
varices (particularly in cases of liver cirrhosis) can be treated
in a manner as described herein as mentioned for other ducts in the
body. Likewise, gastric varices in usually inaccessible locations,
such as the fundus of the stomach, are also suited for treatment
according to the methods and systems disclsoed herein.
[0055] Benign or malignant prostatic conditions, including prostate
cancer and benign prostate hyperplasia (BPA), are also suitable for
treatment via the methods and systems of the present invention.
Restoration of patency to the urethra can be facilitated via energy
ablation treatment (such as via RF) in conjunction with balloon
dilation and/or placement of a stent.
[0056] The disclosure is further illustrated by the following
non-limiting examples.
EXAMPLES
[0057] Description of Device
[0058] The CE marked endoscopic bipolar RF catheter developed and
used in the present examples is called EndoHPB (EMcision Ltd, UK).
EndoHPB was developed by a collaboration between engineers at
Imperial College, University of London and EMcision Ltd, UK.
EMcision Ltd is a company developed out of Imperial College.
[0059] EndoHPB is a single use bipolar radiofrequency catheter. It
is an 8 French (2.7 mm), 1.8 m long nylon tube and is designed to
be used either at PTC or ERC over a 0.035 inch (0.9 mm) guidewire.
If used percutaneously a 10 French (3.3 mm) bore introducer is
required. The outer body of EndoHPB is made of braided pebax 7033,
the inner body of polyimide with a PTFE lining to provide smooth
tracking. At the tip of the device are two stainless steel ring
electrodes spaced 8 mm apart, with the distal electrode 5 mm from
the tip of the device (see FIG. 1). The heating zone length
produced is 25 mm+/-3 mm. EndoHPB can be used with approved
radiofrequency generators. For the present examples the RITA.TM.
1500x RF (Angiodynamics, Queensbury, N.Y.) generator was used,
although the Cosman Coagulator CC-1 (Radionics, Burlington, Mass.)
is also suitable.
Example 1
[0060] Animal Model
[0061] A porcine model was used. Three animals in total were used.
The animals were fasted overnight and allowed free access to water.
They were sedated with an intramuscular injection of 5 mg/kg
azaperone and 10 mg/kg ketamine. In order to reduce salivary and
bronchial secretions atropine at a dose of 0.05 mg/kg was
administered intramuscularly. Anaesthesia was induced with propofol
(2.5-3.5 mg/kg), infused via the auricular vein. All the pigs were
orally intubated and mechanically ventilated (Hallowell-EMC 2000).
Tidal volume was maintained at 10-15 ml/kg, and the respiratory
rate at 14-16 breaths/min. Anaesthesia was maintained with
sevoflurane, administered at 1-1.5 MAC concentration (2.5-3.75%),
in a closed circle system (MDS Matrx, VMS). Finally, buprenorphine
(0.005-0.02 mg/kg intravenously) was administered for
analgesia.
[0062] Interventional Procedure
[0063] A Pentax.TM. side viewing endoscope (ED3440T) was used. The
orifice of the common bile duct was identified and enlarged using
cutting forceps. Under fluoroscopic control a 0.035'' 260 cm hydra
jagwire (Boston Scientific) was inserted into the duct. EndoHPB was
then inserted over the guidewire and connected to a RITA.TM. 1500x
RF generator. EndoHPB was then activated for different time
intervals and wattages along the bile duct. On completion of the
experiment, the animal was killed. Laparotomy was performed to see
if there was any evidence of thermal injury and to allow the common
bile duct to be resected for histology.
[0064] Results
[0065] Use of EndoHPB was found to be compatible with the
Pentax.TM. side viewing endoscope (ED3440T) and could be operated
easily via the 3.2 mm biopsy channel. In the porcine model the
common bile duct was found to be short and more difficult to
cannulate at ERC so EndoHPB was only tested at two different levels
within the bile duct of each animal. Table 1 summarises the power
and time settings of EndoHPB used in each pig, and the amount of
thermal injury observed on histological criteria. On the lower
power settings of 2, 3 and 5 W for one minute duration a mild
thermal injury was seen on microscopy (FIG. 2). When the duration
of 5 W application was increased to 2 minutes a moderate thermal
injury was observed with complete denudation of the biliary
epithelium (FIG. 3). With the higher power setting of 10 W or
greater, the thermal injury became evident at laparotomy (FIG. 4)
and complete coagulation of the common bile duct was produced
preventing EndoHPB from being reintroduced and activated. On
histological assessment severe thermal changes with extensive and
complete coagulative necrosis of the bile duct wall was
demonstrated (FIG. 5).
TABLE-US-00001 TABLE 1 CBD Heating diameter Power Time Thermal (mm)
(watts) (minutes) Injury Pig 1 25 2 1 mild 3 1 mild Pig 2 26 5 1
mild 5 2 moderate Pig 3 25 10 1 severe 20 1 severe
[0066] Conclusion
[0067] This work has established that EndoHPB handles well and is
compatible with use via a side viewing endoscope through a 3.2 mm
biopsy channel. In the context of a normal porcine bile duct the
ideal power setting appeared to be about 5 W for around 2 minutes.
When significantly higher power settings were used problems with
reinsertion and application of EndoHPB into the common bile duct
were encountered. Additionally, a more extensive thermal injury was
produced macroscopically and microscopically which could correlate
with the later development of bile leak, bowel perforation or
pancreatitis.
Example 2
[0068] Background
[0069] The goal of this animal-based investigation was to examine
the ability of RF energy to ablate and coagulate the tissues until
induction of perforation. In this way the maximum parameters for
thermal ablation can be determined.
[0070] Method
[0071] Ten mini pigs underwent general anesthesia. A side viewing
endoscope (Fujinon Inc., NJ) was advanced through the mouth into
the esophagus where a 10 French wire guide RF probe (Habib EndoHPB,
EMcision.TM., UK) was placed in the upper esophagus to apply one
watt (1 W) of energy for one minute, then advanced to the
mid-esophagus to apply three watts (3 W) for 2 minutes, and
finally, to the lower esophagus, where 5 watts (5 W) was applied
for one minute. Five of the 10 animals were then sacrificed and the
esophagus harvested by a dedicated veterinarian and surgeon to
confirm the presence or absence of perforation. The five other pigs
were kept alive for another month and remained healthy. Under
general anesthesia, a repeat procedure was then performed using 50
W for 5 minutes, 30 W for 3 minutes until perforation was obtained
and confirmed endoscopically and macroscopically
[0072] Results
[0073] On both gross and endoscopic examination of the esophagus,
no perforation was noted using the low power settings (i.e. 1 to 5
W). The area where energy was applied appeared paler than the
surrounding tissues indicating the ability to coagulate the areas
to which the energy is applied and sparing the neighboring areas.
Using high power settings (i.e.: 30 or 50 W) leads to perforation
within only a few minutes of application.
[0074] Conclusions
[0075] The RFA device can provide enough controlled energy through
the endoscope to induce tissue coagulation and ablation without
inducing perforation when used at low wattage power settings. Its
ability to be advanced over a wire and offer different levels of
energy constitutes a tremendous potential for palliation of
intraluminal cancerous obstruction.
Example 3
[0076] Background
[0077] Patients with un-resectable pancreatic or bile duct cancer
were recruited. Exclusion criteria were: uncorrected coagulopathy,
cardiac pacemaker, failure to insert guide-wire across biliary
stricture, Karnofsky score less than 40% (Karnofsky, D. A.,
Abelmann W H, Craver L F, Burchenal J H, The use of the nitrogen
mustards in the palliative treatment of carcinoma. With particular
reference to bronchogenic carcinoma. Cancer, 1948. 1(4): p.
634-656) and inability to give informed consent. Prospective data
was collected detailing ERCP complications, patient survival and
stent patency up to 90 days post procedure, with serial liver
function tests (and imaging where indicated) used to determine post
ERCP biliary obstruction.
[0078] Intervention
[0079] Study ERCP with radiofrequency ablation (RFA) catheter was
performed by experienced pancreatobiliary endoscopists. ERCP was
performed under standard operating conditions with Olympus TJF-260
duodenoscopes (Olympus UK, Essex, UK). Previously placed plastic
stents were removed prior to study cholangiography which then
confirmed biliary stricture length and position. The RFA catheter
was placed under fluoroscopic guidance across the biliary
stricture, see FIG. 7(b).
[0080] The Habib.TM. EndoHPB (EMcision, UK) catheter used in this
Example has FDA (USA Food and Drug Administration) and CE approval
(European Union European Conformity). It is a bipolar RFA probe
that is 8 Fr (2.6 mm), 1.8m long, compatible with standard (3.2 mm
working channel) side viewing endoscopes and passes over 0.035''
guide wires. The catheter has 2 ring electrodes 8 mm apart with the
distal electrode 5 mm from the leading edge providing local
coagulative necrosis over a 2.5 cm length, FIG. 1.
[0081] Energy was delivered by an RFA generator (1500 RF generator,
Rita Medical Inc, USA) delivering electrical energy at 400 kHz at
7-10 W for 2 minutes with a rest period of 1 minute prior to moving
the catheter. Depending on the length of the stricture sequential
applications were applied to ensure RFA treatment throughout the
length of the stricture without significant overlap of treated
areas. After RFA treatment uncovered SEMS (Wallstent, Boston
Scientific, USA) were deployed as per standard protocols.
[0082] Trial Design
[0083] The design was a single centre open label pilot study to
demonstrate safety and efficacy.
[0084] Results
[0085] 22 patients were recruited to this pilot study between
January 2009 and April 2010. Patient data is shown in Table 2. In
one patient irretrievable proximal migration of a plastic stent
resulted in no attempt to deploy the RFA catheter; a standard SEMS
procedure was undertaken. SEMS placement was achieved in all cases
of EndoHPB deployment. There were no technical difficulties placing
the RFA catheter across the biliary stricture. Six study subjects
had evidence of hepatic hilar or intra hepatic involvement. Three
of these subjects underwent balloon dilatation of the stricture to
facilitate further instrumentation. No attempt was made to place
multiple SEMS in these patients at study ERCP. Asymptomatic
biochemical pancreatitis (amylase 1450 U/I) developed post-ERCP in
only one patient. Two patients developed cholecystitis requiring
cholecystostomy; both these patients had tumour encasement of the
cystic duct on abdominal CT scan and pre ERCP sepsis. One patient
developed rigors post ERCP that settled after empiric antibiotic
therapy. One patient did not demonstrate biliary decompression;
subsequent review concluded there was significant intra-hepatic sub
segmental biliary malignancy precluding successful biliary
decompression.
[0086] 30 day patency was maintained in all other patients with no
30 day mortality. At 90 day follow up the patient who failed to
demonstrate biliary decompression had died, one further patient had
died of disease progression with stent patent. Three other patients
had developed biliary obstruction. Further RFA procedure data is
summarised in Table 3.
[0087] Discussion
[0088] This trial represents a phase 1 study of endobiliary RFA
treatment of malignant biliary obstruction and clearly demonstrates
immediate and 30 day safety and 90 day efficacy.
[0089] Potential complications that were identified in pre-clinical
animal models (such as in Examples 1 and 2) included extension of
the RFA burn into local structures and difficulty reintroducing
catheters into the bile duct after RFA treatment, but these
complications were not apparent in the patients treated in this
trial. Haemorrhage and abscess formation at the site of RFA, which
are recognised complications of hepatic RFA did not occur in this
study population (Mulier, S., et al., Radiofrequency ablation
versus resection for resectable colorectal liver metastases: time
for a randomized trial? An update. Dig Surg, 2008. 25(6): p.
445-60).
[0090] This is the first reported use of endo-biliary RFA and the
reported complications in this pilot study are in keeping with
literature reported type and incidence for biliary SEMS (Loew, B.
J., et al., Comparative performance of uncoated, self expanding
metal biliary stents of different designs in 2 diameters: final
results of an international multicenter, randomized, controlled
trial. Gastrointest Endosc, 2009. 70(3): p. 445-53).
[0091] Application of RFA within the bile duct induces local
coagulative necrosis. RFA coagulative necrosis within a malignant
biliary stricture will likely result in some damage to adjacent
healthy bile duct, however, the use of two electrodes means that
the heating pattern is substantially cylindrical and is stretched
between the two electrodes. In this way the energy is spread over a
larger volume than with a single electrode, and the spatial
variation of energy deposition is less. In any case since the RFA
burn was immediately followed by insertion of SEMS any potential
biliary injury was empirically treated. Prospective data to
determine the best treatment of bile duct injury in this situation
is lacking, however with traumatic or surgical bile duct injuries
endoscopic biliary stent placement is considered the best form of
therapy (de Reuver, P. R., et al., Endoscopic treatment of
post-surgical bile duct injuries: long term outcome and predictors
of success. Gut, 2007. 56(11): p. 1599-605). There were no
complications that could be attributed to full thickness bile duct
RFA, nor was there any evidence of biliary leak during the 30 day
follow up period.
[0092] This trial demonstrates 30 day safety and 90 day efficacy in
human patients of the described disclosure.
TABLE-US-00002 TABLE 2 Demographics N = 22 Sex: male 11 Age
mean/range years 70 (56-84) Pancreatic/cholangiocarcinoma 16/6
Metastatic N = 10 Locally advanced N = 17 Metastatic and locally
advanced N = 7 Declined surgery N = 2 Hilar stricture N = 6 Plastic
stent prior to SEMS N = 16 Sepsis at RFA ERCP N = 7 Bilirubin
median/range, .mu.mol/l 26 (4-286) Karnofsky score median/range 55
(40-100)
TABLE-US-00003 TABLE 3 RFA Procedure details N = 21 Procedure time,
mean/range, minutes 43 (22-68) Fluoroscopic screening time, 5
(3-36) median/range, minutes Number of applications, median/range 2
(1-4) Total energy delivered, mean/range, 2474 (1200-3600) Joules
Stricture diameter pre RFA, 0 (0-1) median/range, mm Stricture
diameter post RFA, 4 (3-6) median/range, mm Length of stricture,
mean/range, mm 37 (20-60) Post ERCP day stay, median/range, 1
(1-24) days Patients alive with biliary patency 16/21 (76%) at 90
days (%)
[0093] According to some exemplary implementations, the components
of devices disclosed herein may be provided in any combination to
accomplish desired functionality. Likewise, operations of methods
disclosed may be provided in any sequence or combination to achieve
results as disclosed herein.
[0094] While the method and agent have been described in terms of
what are presently considered to be the most practical and
preferred exemplary implementations, it is to be understood that
the disclosure need not be limited to the disclosed exemplary
implementations. It is intended to cover various modifications and
similar arrangements included within the spirit and scope of the
claims, the scope of which should be accorded the broadest
interpretation so as to encompass all such modifications and
similar structures. The present disclosure includes any and all
exemplary implementations of the following claims.
[0095] It should also be understood that a variety of changes may
be made without departing from the essence of the invention. Such
changes are also implicitly included in the description. They still
fall within the scope of this invention. It should be understood
that this disclosure is intended to yield a patent covering
numerous aspects of the invention both independently and as an
overall system and in both method and apparatus modes.
[0096] Further, each of the various elements of the invention and
claims may also be achieved in a variety of manners. This
disclosure should be understood to encompass each such variation,
be it a variation of an exemplary implementation of any apparatus
implementation, a method or process implementation, or even merely
a variation of any element of these.
[0097] Particularly, it should be understood that as the disclosure
relates to elements of the invention, the words for each element
may be expressed by equivalent apparatus terms or method
terms--even if only the function or result is the same.
[0098] Such equivalent, broader, or even more generic terms should
be considered to be encompassed in the description of each element
or action. Such terms can be substituted where desired to make
explicit the implicitly broad coverage to which this invention is
entitled.
[0099] It should be understood that all actions may be expressed as
a means for taking that action or as an element which causes that
action.
[0100] Similarly, each physical element disclosed should be
understood to encompass a disclosure of the action which that
physical element facilitates.
[0101] Any patents, publications, or other references mentioned in
this application for patent are hereby incorporated by reference.
In addition, as to each term used it should be understood that
unless its utilization in this application is inconsistent with
such interpretation, common dictionary definitions should be
understood as incorporated for each term and all definitions,
alternative terms, and synonyms such as contained in at least one
of a standard technical dictionary recognized by artisans and the
Random House Webster's Unabridged Dictionary, latest edition are
hereby incorporated by reference.
[0102] Finally, all referenced listed in the Information Disclosure
Statement or other information statement filed with the application
are hereby appended and hereby incorporated by reference; however,
as to each of the above, to the extent that such information or
statements incorporated by reference might be considered
inconsistent with the patenting of this/these invention(s), such
statements are expressly not to be considered as made by the
applicant(s).
[0103] In this regard it should be understood that for practical
reasons and so as to avoid adding potentially hundreds of claims,
the applicant has presented claims with initial dependencies
only.
[0104] Support should be understood to exist to the degree required
under new matter laws--including but not limited to United States
Patent Law 35 USC 132 or other such laws--to permit the addition of
any of the various dependencies or other elements presented under
one independent claim or concept as dependencies or elements under
any other independent claim or concept.
[0105] To the extent that insubstantial substitutes are made, to
the extent that the applicant did not in fact draft any claim so as
to literally encompass any particular exemplary implementation, and
to the extent otherwise applicable, the applicant should not be
understood to have in any way intended to or actually relinquished
such coverage as the applicant simply may not have been able to
anticipate all eventualities; one skilled in the art, should not be
reasonably expected to have drafted a claim that would have
literally encompassed such alternative exemplary
implementations.
[0106] Further, the use of the transitional phrase "comprising" is
used to maintain the "open-end" claims herein, according to
traditional claim interpretation. Thus, unless the context requires
otherwise, it should be understood that the term "compromise" or
variations such as "comprises" or "comprising", are intended to
imply the inclusion of a stated element or step or group of
elements or steps but not the exclusion of any other element or
step or group of elements or steps.
[0107] Such terms should be interpreted in their most expansive
forms so as to afford the applicant the broadest coverage legally
permissible.
* * * * *