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Weight Loss Patent Abstract
Method and system for ablating selected portions of the gastrointestinal
(GI) tract to provide therapy or alleviate symptoms for GI tract
or liver tumors, obesity, motility disorders, GERD, or to induce
weight loss. The ablation procedure may be performed endogastrically
via mouth and esophagus in an anesthetized patient. Alternatively,
the ablations may be performed epigastrically using laproscopic
tools. The ablation may involve one of the following: a) ablating
tissues of the gastrointestinal (GI) tract; b) ablating tissues
of the liver; c) disruption of pacemaker region of the stomach;
d) disruption of muscle layers of gastric wall; e) vagal nerve(s)
disruption; f) ablation of endogastric lining for cells that produce
the hunger hormone ghrelin; and g) disruption of enteric nervous
system. The technology used may be one from a group comprising:
1) Radiofrequency catheter ablation; 2) Radiofrequency ablation
using an irrigated tip catheter; 3) Microwave ablation; 4) Cryoablation;
5) High intensity focused ultrasound (HIFU) ablation; and 6) Laser
ablation.
Weight Loss Patent Claims
1. A method of providing selective ablations to part(s) of gastrointestinal
(GI) tract for treating or alleviating the symptoms of at least
one of gastrointestinal tumors, obesity, motility disorders, GERD,
or to induce weight loss, comprising the steps of: a) selecting
a patient for said selective ablation; b) selecting one or more
sites for said selective ablation; c) selecting one or more kind
of ablation means to provide said selective ablation; d) selecting
the intensity of ablations for said one or more sites; and e) providing
said ablation by at least one of radiofrequency (RF) catheter ablation
means, radiofrequency ablation with irrigated catheter means, microwave
ablation means, high intensity focused ultrasound ablation means,
cryoablation means, and laser ablation means.
2. The method of claim 1, wherein said radiofrequency energy is
delivered between approximately 300 KHz and 1,000 K Hz.
3. The method of claim 1, wherein said microwave is provided at
approximately 915 MHz or approximately 2,450 MHz.
4. The method of claim 1, wherein said ablations are directed to
gastric muscle.
5. The method of claim 1, wherein said ablations are directed to
gastric muscle and nerve tissue.
6. A method of selectively ablating portions of gastrointestinal
(GI) tract or liver to provide adjunct (add-on) therapy or alleviate
symptoms for at least one of gastrointestinal tumors, obesity, motility
disorders, GERD, or to induce weight loss, with radiofrequency catheter
ablation or microwave ablation, comprising the steps of: a) selecting
a patient to be ablated; b) selecting portions of gastrointestinal
(GI) tissue to be ablated in said patient; and c) providing said
ablation by one of radiofrequency catheter ablation means comprising,
a radiofrequency ablation generator, a ground patch connected to
patient and said radiofrequency ablation generator, and a catheter
adapted for reaching said portions of gastrointestinal (GI) tract
to be ablated; or microwave ablation means, comprising a catheter
antenna adapted for reaching portions of gastrointestinal (GI) tract
being ablated, and a microwave ablation generator, wherein said
microwave ablation generator further comprises a microwave source,
coupling network, and a power supply.
7. The method of claim 6, wherein said radiofrequency energy is
delivered between approximately 300 KHz and 1,000 K Hz.
8. The method of claim 6, wherein said microwave energy is provided
at approximately 915 MHz or approximately at 2,450 MHz.
9. The method of claim 6, wherein said ablation is applied to a
gastric wall.
10. The method of claim 6, wherein said ablation is directed to
gastric mucosa.
11. The method of claim 6, wherein said ablation of said gastric
wall may use epigastric approach or endogastric approach.
12. The method of claim 6, wherein said ablation may involve ablation
to nerve tissue around the stomach.
13. The method of claim 12, wherein said nerve tissue may be part
of enteric nervous system.
14. The method of claim 12, wherein said nerve tissue may be part
of vagus nerve tissue, or branches, or parts thereof.
15. The method of claim 6, wherein said ablation is applied to
a endogastric lining of the stomach wall.
16. A method of selectively ablating portions of gastrointestinal
(GI) tract or liver to provide adjunct (add-on) therapy or alleviate
symptoms for at least one of gastrointestinal tumors, obesity, motility
disorders, GERD, or to induce weight loss, with high intensity focused
ultrasound (HIFU) ablation, comprising the steps of: a) selecting
a patient to be ablated; b) selecting portions of gastrointestinal
(GI) tissue to be ablated in said patient; and c) providing an ultrasound
applicator adapted for applying ultrasound energy to said gastrointestinal
(GI) tissue to be ablated; and d) providing an electromechanical
component means for steering and positioning acoustic beam, a display
therapy planning and imaging, and a computer for HIFU dosage calculation,
control and for monitoring feedback during ablation.
17. The method of claim 16, wherein said ablation is for ablating
vagus nerve(s), or branches or parts thereof.
18. The method of claim 16, wherein said ablation is applied in
the esophagus, close to a lower esophageal sphincter (LES).
19. The method of claim 16, wherein said ablations are applied
close to lesser curvature of the stomach.
20. The method of claim 16, wherein said ablation are applied with
a frequency of around 5 MHz.
Weight Loss Patent Description
[0001] This application is related to a co-pending application entitled
"Method and system for gastric ablation and gastric pacing
to provide therapy for obesity, motility disorders, or to induce
weight loss" filed Jun. 29, 2005.
FIELD OF INVENTION
[0002] This invention relates generally to medical ablation of
tissues, more specifically to gastrointestinal (GI) tract ablations
including ablations of liver, stomach or surrounding tissue to provide
therapy for GI tumors, obesity, motility disorders, GERD, or to
induce weight loss.
BACKGROUND
[0003] Obesity is a significant health problem in the United States
and many other developed countries. Obesity results from excessive
accumulation-of-fat in the body. It is caused by ingestion of greater
amounts of food than can be used by the body for energy. The excess
food, whether fats, carbohydrates, or proteins, is then stored almost
entirely as fat in the adipose tissue, to be used later for energy.
Obesity is not simply the result of gluttony and a lack of willpower.
Rather, each individual inherits a set of genes that control appetite
and metabolism, and a genetic tendency to gain weight that may be
exacerbated by environmental conditions such as food availability,
level of physical activity and individual psychology and culture.
Other causes of obesity include psychogenic, neurogenic, and other
metabolic related factors.
[0004] Obesity is defined in terms of body mass index (BMI), which
provides an index of the relationship between weight and height.
The BMI is calculated as weight (in Kilograms) divided by height
(in square meters), or as weight (in pounds) times 703 divided by
height (in square inches). The primary classification of overweight
and obesity relates to the BMI and the risk of mortality. The prevalence
of obesity in adults in the United States without coexisting morbidity
increased from 12% in 1991 to 17.9% in 1998.
[0005] Treatment of obesity depends on decreasing energy input
below energy expenditure. Treatment has included among other things
various drugs, starvation and even stapling or surgical resection
of a portion of the stomach. Surgery for obesity has included gastroplasty
and gastric bypass procedure. Gastroplasty which is also known as
stomach stapling, involves constructing a 15- to 30 mL pouch along
the lesser curvature of the stomach. A modification of this procedure
involves the use of an adjustable band that wraps around the proximal
stomach to create a small pouch. Both gastroplasty and gastric bypass
procedures have a number of complications.
[0006] This Application discloses use of various types of ablation
technologies for ablating the gastrointestinal tract for GI tumors,
liver tumors, or for ablating the stomach or adjacent areas from
the epigastric side or the endogastric side to provide therapy or
alleviate symptoms. The ablation technology may be one or more from
a group comprising:
[0007] a) Radiofrequency catheter ablation
[0008] b) Radiofrequency ablation using irrigated tip catheter
[0009] c) Microwave ablation
[0010] d) Cryoablation
[0011] e) High intensity focused ultrasound (HIFU) ablation; and
[0012] f) Laser ablation
[0013] The ablation site or structure may be one from a group comprising:
[0014] a) Tissues of the gastrointestinal (GI) tract;
[0015] b) Tissues of the liver;
[0016] c) Disruption of pacemaker region of the stomach;
[0017] d) Disruption of muscle layers of gastric wall;
[0018] e) Vagal nerve(s) disruption;
[0019] f) Ablation of endogastric lining for cells that produce
the hunger hormone ghrelin; and
[0020] e) Disruption of enteric nervous system.
[0021] Background of Gastrointestinal (GI) Physiology and Regulation
[0022] Shown in conjunction with FIG. 1, the gastrointestinal (GI)
tract is a continuous muscular digestive tube that winds through
the body. The organs of the GI tract are the mouth, pharynx (not
shown), esophagus 3, stomach 54, small intestine (duodenum 7, jejunum,
and ileum), and large intestine (cecum, ascending colon, transverse
colon, and descending colon).
[0023] The gastrointestinal (GI) tract has a nervous system all
its own, which is the enteric nervous system 9. This is shown in
conjunction with FIG. 2. It lies entirely in the wall of the gut,
beginning in the esophagus 3 and extending all the way to the anus.
The enteric nervous system has about 100 million neurons, almost
exactly equal to the number in the entire spinal cord. It especially
controls gastrointestinal movements and secretion. The enteric nervous
system is composed mainly of the two plexuses, 1) the myenteric
plexus 10, which is the outer plexus lying between the longitudinal
and circular muscle layers, and 2) the submucosal plexus 11 that
lies in the submucosa. The nervous connection within and between
these two plexuses is depicted in FIG. 2. The myenteric plexus controls
mainly the gastrointestinal movements, and the submucosal plexus
controls mainly gastrointestinal secretion and local blood flow.
As also depicted in FIG. 2, the sympathetic and parasympathetic
fibers connect with the myenteric 10 and the submocosal 11 plexus.
Although the enteric nervous system can function on its own, stimulation
by the parasympathetic 12 and sympathetic 13 systems can further
activate or inhibit gastrointestinal functions. The autonomic nerves
influence the functions of the gastrointestinal tract by modulating
the activities of neurons of the enteric nervous system 9.
[0024] Shown in conjunction with FIG. 2, sympathetic innervation
of the gastrointestinal tract is mainly via postganglionic adrenergic
fibers whose cell bodies are located in pre-vertebral and parabertabral
ganglia. The celiac, superior and inferior mesenteric, and hypogastric
plexus provide sympathetic innervation to various segments of the
GI tract. Activation of the sympathetic nerves usually inhibits
the motor and secretory activities of the GI system.
[0025] Parasympathetic innervation of the GI tract down to the
level of the transverse colon is provided by branches of the vagus
nerves (10.sup.th cranial nerve). Excitation of parasympathetic
nerves usually stimulates the motor and secretory activities of
the GI tract.
[0026] The stomach 54 is richly innervated by extrinsic nerves
and by the neurons of the enteric nervous system 9. Axons from the
cells of the intramural plexus innervate smooth muscle and secretory
cells.
[0027] The emptying of gastric contents is regulated by both neural
and hormonal mechanisms. The duodenal and jejunal mucosa contain
receptors that sense acidity, osmotic pressure, certain fats and
fat digestion products, and peptides and amino acids The chyme that
leaves the stomach is usually hypertonic and it becomes even more
hypertonic because of the action of the digestive enzymes in the
duodenum. Gastric emptying is slowed by hypertonic solutions in
the duodenum, by duodenal pH below 3.5, and by the presence of amino
acids and peptides in the duodenum, The presence of fatty acids
or monoglycerides (products of fat digestion) in the duodenum also
dramatically decreases the rate of gastric emptying.
[0028] Parasympathetic innervation to the stomach is supplied by
the vagus nerves, while sympathetic innervation to the stomach is
provided by the celiac plexus. In general, parasympathetic nerves
stimulate gastric smooth muscle motility and gastric secretions,
whereas sympathetic activity inhibits these function. Numerous sensory
afferent fibers leave the stomach in the vagus nerves; some of these
fibers travel with sympathetic nerves. Other sensory neurons are
the afferent links between sensory receptors and the intramural
plexuses of the stomach. Some of these afferent fibers relay information
intragastric pressure, gastric distention, intragastric pH, or pain.
[0029] Shown in conjunction with FIG. 3 is the fundus 15, the body
17, and antrum 19 of the stomach 54. After eating, when a wave of
esophageal peristalsis begins, a reflex causes the LES to relax.
This relaxation of the LES is followed by receptive relaxation of
the fundus 15 and body 17 of the stomach. The stomach 54 will also
relax if it is filled directly with gas or liquid. The nerve fibers
in the vagi are a major efferent pathways for reflex relaxation
of the stomach 54.
[0030] FIG. 4 depicts the three main muscle layers of the stomach
54, which are the longitudinal layer 14, the circular layer 16,
and the oblique layer 18. The complex and coordinated activity of
these muscle layers is responsible for the normally efficient gastric
motility. Whereas, the gastric pacing disclosed here from around
the antral area of the stomach 54, disrupts the normal gastric motility.
[0031] Normally, the smooth muscle of the GI tract is excited by
almost continual slow, intrinsic. electrical activity along the
membranes of the muscle fibers. This activity has two basic types
of electrical waves: 1) slow waves and 2) spikes. This is shown
in conjunction with FIG. 5. Most gastrointestinal contractions occur
rhythmically, and this rhythm is determined mainly by the frequency
of the slow waves of the smooth muscle membrane potential. Their
intensity usually varies between 5 and 15 millivolts, and their
frequency ranges in different parts of the human gastrointestinal
tract between 3 and 12 per minute. The rhythm of contraction of
the body of the stomach is about 3 per minute (and in the duodenum
is about 12 per minute).
[0032] The electrical activity of the GI tract is shown in conjunction
with FIG. 5. For example, the contraction of small intestinal smooth
muscle occurs when the depolarization caused by the slow wave exceeds
a threshold for contraction. When depolarization of a slow wave
exceeds the electrical threshold, a burst of action potentials 19
occurs. The action potentials elicit a much stronger contraction
than occurs in the absence of action potentials. The contractile
force increases with increasing number of action potentials.
[0033] Action potentials in gastrointestinal smooth muscle are
more prolonged (10 to 20 msec) than those of skeletal muscle and
have little or no overshoot. The rising phase of the action potentials
is caused by ion flow through channels that conduct both Ca.sup.++
and Na.sup.+ and are relatively slow to open. Ca.sup.++ that enters
the cell during the action potential helps to initiate contraction.
[0034] When the membrane potential of gastrointestinal smooth muscle
reaches the electrical threshold, typically near the peak of a slow
wave, a train of action potentials (1 to 10/sec) is fired. The extent
of depolarization of the cells and the frequency of action potentials
are enhanced by some hormones and paracrine agonists and by compounds
liberated from excitatory nerve endings. Inhibitory hormones and
neuroefector substances hyperpolarize the smooth muscle cells and
may diminish or abolish action potential spikes.
[0035] Slow waves that are not accompanied by action potentials
elicit weak contractions of the smooth muscle cells (FIG. 5). Much
stronger contractions are evoked by the action potentials that are
intermittently triggered near the peaks of the slow waves. The greater
the frequency of action potentials that occur at the peak of a slow
wave, the more intense is the contraction of the smooth muscle.
Because smooth muscle cells contract rather slowly (about one tenth
as fast as skeletal muscle cells), the individual contraction caused
by each action potential in a train do not cause distinct twitches;
rather, they sum temporally to produce a smoothly increasing level
of tension (FIG. 5).
[0036] Between trains of action potentials the tension developed
by gastrointestinal smooth muscle falls, but not to zero. This nonzero
resting, or baseline, tension of smooth muscle is called tone. The
tone of gastrointestinal smooth muscle is altered by neuroeffectors,
hormones, paracrine substances, and drugs.
[0037] Control of the contractile and secretory activities of the
gastrointestinal tract involves the central nervous system, the
enteric nervous system, and hormones and paracrine substances. The
autonomic nervous system typically only modulates the patterns of
muscular and secretary activity; these activities are controlled
more directly by the enteric nervous system.
[0038] In the current invention, ablation of stomach (gastric)
wall or surrounding tissue such as nerve tissue renders the stomach
to empty less efficiently. This causes a general feeling of "fullness",
and the patients are not as hungry, which ultimately results in
weight loss.
PRIOR ART
[0039] U.S. Pat. No. 6,427,089 (Knowlton) is generally directed
to using microwave energy to modifying the stomach wall of a patient.
[0040] U.S. patent application publication no. 2004/0181178 (Aldrich
et al.), application Ser. No. 10/389,236 is generally directed to
use of transesophageal delivery of energy to interrupt the function
of vagal nerves.
[0041] U.S. patent application publication no. 2004/0215180 (Starkbaum
et al.), application Ser. No. 10/424,010 is generally directed to
ablation of mucosal tissue to inhibit ghrelin production.
[0042] U.S. patent application publication no. 2005/0096638 (Starkbaum
et al.), application Ser. No. 10/699,207, is generally directed
to ablating tissue from an exterior surface of a stomach.
SUMMARY OF THE INVENTION
[0043] In the method and system of this invention ablation is performed
to provide therapy or alleviate symptoms for at least one of gastrointestinal
tumors, liver tumors, obesity, motility disorders, GERD, or to induce
weight loss, using one of various ablation methods.
[0044] Accordingly, it is one object of the invention, to ablate
tumor tissues of the gastrointestinal (GI) tract using one of radiofrequency
catheter ablation, radiofrequency catheter ablation using irrigated
tip catheter, microwave ablation, cryoablation, high intensity focused
ultrasound ablation, or laser ablation.
[0045] It is another object of the invention, to ablate tumor tissues
of the liver using one of radiofrequency catheter ablation, radiofrequency
catheter ablation using irrigated tip catheter, microwave ablation,
cryoablation, high intensity focused ultrasound ablation, or laser
ablation.
[0046] It is another object of the invention, to disrupt pacemaker
region of the stomach using one of radiofrequency catheter ablation,
radiofrequency catheter ablation using irrigated tip catheter, microwave
ablation, cryoablation, high intensity focused ultrasound ablation,
or laser ablation.
[0047] In one aspect ablations to the pacemaker region of the stomach
may be performed using endogastric approach.
[0048] In one aspect ablations to the pacemaker region of the stomach
may be performed using epigstric approach.
[0049] It is another object of the invention, to ablate the muscle
layers of gastric wall, using one of radiofrequency catheter ablation,
radiofrequency catheter ablation using irrigated tip catheter, microwave
ablation, cryoablation, high intensity focused ultrasound ablation,
or laser ablation.
[0050] It is another object of the invention, to ablate vagus nerve(s)
tissues around the esophagus or lessor curvature of the stomach
using one of radiofrequency catheter ablation, radiofrequency catheter
ablation using irrigated tip catheter, microwave ablation, cryoablation,
high intensity focused ultrasound ablation, or laser ablation.
[0051] It is another object of the invention, to ablate endogastric
lining of the stomach using one of radiofrequency catheter ablation,
radiofrequency catheter ablation using irrigated tip catheter, microwave
ablation, cryoablation, high intensity focused ultrasound ablation,
or laser ablation.
[0052] It is yet another object of the invention, to ablate nerve
tissue of the enteric nervous system using one of radiofrequency
catheter ablation, radiofrequency catheter ablation using irrigated
tip catheter, microwave ablation, cryoablation, high intensity focused
ultrasound ablation, or laser ablation.
[0053] These and other objects are provided by one or more of the
embodiments described below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] For the purpose of illustrating the invention, there are
shown in accompanying drawing forms which are presently preferred,
it being understood that the invention is not intended to be limited
to the precise arrangement and instrumentalities shown.
[0055] FIG. 1 is a diagram showing general anatomy of the gastrointestinal
(GI) tract.
[0056] FIG. 2 is a diagram showing control of the enteric nervous
system by the autonomic nervous system (parasympathetic and sympathetic).
[0057] FIG. 3 is a diagram showing general anatomy of the human
stomach.
[0058] FIG. 4 is a diagram showing the longitudinal, circular,
and oblique muscle layers of the stomach.
[0059] FIG. 5 is a diagram depicting the electrical activity of
the GI tract.
[0060] FIG. 6 depicts epigastric approach to ablation utilizing
laproscopic surgery.
[0061] FIG. 7 depicts endogastric approach to ablation via the
mouth and esophagus.
[0062] FIG. 8A is a simplified block diagram of a radiofrequency
ablation system.
[0063] FIG. 8B shows a ground patch, and ground patch placement
for radiofrequency ablation.
[0064] FIG. 9A depicts an area of resistive heating for radiofrequency
ablations.
[0065] FIG. 9B depicts temperature regions for gastric ablations.
[0066] FIG. 10A is a simplified schematic for radiofrequency ablation
generator, showing voltage, current, and temperature monitoring.
[0067] FIG. 10B is a simplified schematic showing power and impedance
as derivatives of voltage and current.
[0068] FIG. 11 is a simplified schematic showing the display elements
of a radiofrequency ablation generator.
[0069] FIG. 12 is a simplified block diagram showing the elements
of a microwave ablation system.
[0070] FIG. 13 is a diagram showing the principle of high intensity
focused ultrasound (HIFU).
[0071] FIG. 14 is a simplified block diagram of an ultrasound hyperthermia
system.
[0072] FIG. 15 is a simplified block diagram of housing for an
ultrasound applicator.
[0073] FIG. 16 depicts catheter end of an ultrasound ablation system.
[0074] FIG. 17 depicts catheter end of a cryoablation probe.
[0075] FIG. 18 is cross-section of cryoablation probes.
[0076] FIG. 19 is a diagram showing the elements of a laser ablation
system.
[0077] FIG. 20 is a simplified diagram showing the principle of
a laser ablation system.
[0078] FIG. 21 is a simplified block diagram showing the elements
of a laser ablation system.
[0079] FIG. 22 is a simplified diagram of a laser ablation system.
[0080] FIG. 23 is a diagram depicting the gastrointestinal tract.
[0081] FIG. 24 is a diagram of the stomach showing areas for ablation
from the endogastric side and epigastric side.
[0082] FIG. 25 is a diagram of the stomach showing areas for ablation
from the epigastric side.
[0083] FIG. 26 is a graph showing the levels of ghrelin during
the day, corresponding with breakfast B, lunch L, and dinner D.
[0084] FIG. 27A is a diagram showing an ablation catheter in the
esophagus, near the lower esophageal sphincter.
[0085] FIG. 27B is a diagram of the ablation catheter of FIG. 27A.
[0086] FIGS. 28A, 28B, and 28C depict ablation in the lower esophageal
region.
DESCRIPTION OF THE INVENTION
[0087] In the method and system of this invention, ablation of
stomach and/or other parts of the gastrointestinal (GI) tract is
performed to provide therapy for at least one of gastrointestinal
tumors, liver tumors, obesity, to induce weight loss, as well as
other gastrointestinal (GI) disorders.
[0088] The ablation of stomach may be performed from the epigastric
side (shown in FIG. 6) or from endogastric side within the stomach
wall (shown in FIG. 7). Referring to FIG. 6, for epigastric ablation,
the ablation catheter is inserted into the abdominal cavity laproscopically,
and ablation lesions are performed on the epigastric surface of
the stomach. For performing the ablation procedure, using the epigastric
approch, the patient is positioned in the lithotomy position and
anesthetized. The abdomen is cleansed with an antiseptic solution
and draped in a sterile fashion. The trocars 45A, and 45B are inserted.
One trocar 45A is needed for introducing the ablation catheter 26.
A second trocar 45B is needed for introducing the optical system.
An optional third trocar can be used to introduce a liver retractor.
[0089] After retracting the liver, the optical system is used for
identifying the anatomical structure to be ablated. Different forms
of ablation energies may used, such as radiofrequency (RF) catheter
ablation, RF ablation with an irrigated tip catheter, microwave
ablation, high intensity focused ultrasound (HIFU) ablation, cryoablation,
and laser ablation. These are further described later in this disclosure.
[0090] Alternatively, the ablation may be performed from the endogastric
side (FIG. 7). Combination of epigastric and endogastric ablations
may also be performed. As one example without limitation, a patient
may have epigastric ablation procedure performed, and at a later
date may have endogastric ablation procedure, or vice versa.
[0091] As shown in conjunction with FIG. 7, for endogastric ablations,
the ablation catheter 26 may be introduced in an anesthetized patient,
via the mouth and esophagus, and positioned at the appropriate site
within the stomach 54. Even though FIG. 7 is shown in reference
to radiofrequency (RF) ablation, other forms of ablation energies
may also be used such as RF with irrigated tip catheter, microwave
energy, cryoablation, high intensity focused ultrasound (HIFU) ablation,
cryoablation, and laser ablation.
[0092] Table one below, summarizes the ablation technology that
may be used, as well as, the ablation site or structure at or around
the stomach, such as the nerve plexus that carry hunger or satiety
signals to the brain. TABLE-US-00001 TABLE 1 ABLATION TECHNOLOGY
ABLATION SITE OR STRUCTURE 1. Radiofrequency catheter 1. Tumor issues
of the ablation gastrointestinal (GI) tract 2. Radiofrequency irrigated
tip 2. Tumor tissues of the liver catheter ablation 3. Microwave
ablation 3. Disruption of pacemaker region of the stomach 4. Cryoablation
4. Disruption of muscle layers of gastric wall 5. High intensity
focused 5. Vagal nerve(s) disruption ultrasound (HIFU) ablation
6. Laser ablation 6. Ablation of endogastric lining- for cells that
produce the hunger hormone ghrelin 7. Disruption of enteric nervous
system
[0093] In the method of this disclosure, the following combinations
can be practiced:
[0094] 1) Ablation of gastrointestinal (GI) tissues using, a) Radiofrequency
catheter ablation, b) Radiofrequency catheter ablation using irrigated
tip catheter, c) Microwave ablation, d) Cryoablation, e) High intensity
focused ultrasound ablation, and f) Laser ablation.
[0095] 2) Ablation of Liver tissues or liver tumors using, a) Radiofrequency
catheter ablation, b) Radiofrequency catheter ablation using irrigated
tip catheter, c) Microwave ablation, d) Cryoablation, e) High intensity
focused ultrasound ablation, and f) Laser ablation.
[0096] 3) Disruption of pacemaker region of the stomach using,
a) Radiofrequency catheter ablation, b) Radiofrequency catheter
ablation using irrigated tip catheter, c) Microwave ablation, d)
Cryoablation, e) High intensity focused ultrasound ablation, and
f) Laser ablation.
[0097] 4) Disruption of muscle layers of gastric wall, using a)
Radiofrequency catheter ablation, b) Radiofrequency catheter ablation
using irrigated tip catheter, c) Microwave ablation, d) Cryoablation,
e) High intensity focused ultrasound ablation, and f) Laser ablation.
[0098] 5) Vagus nerve disruption using, a) Radiofrequency catheter
ablation, b) Radiofrequency catheter ablation using irrigated tip
catheter, c) Microwave ablation, d) Cryoablation, e) High intensity
focused ultrasound ablation, and f) Laser ablation.
[0099] 6) Ablation of endogastric lining--for cells that produce
the hunger hormone ghrelin using, a) Radiofrequency catheter ablation,
b) Radiofrequency catheter ablation using irrigated tip catheter,
c) Microwave ablation, d) Cryoablation, e) High intensity focused
ultrasound ablation, and f) Laser ablation.
[0100] 7) Disruption of enteric nervous system using, a) Radiofrequency
catheter ablation, b) Radiofrequency catheter ablation using irrigated
tip catheter, c) Microwave ablation, d) Cryoablation, e) High intensity
focused ultrasound ablation, and f) Laser ablation.
Radiofrequency Ablation
[0101] RF ablation is shown with reference to FIGS. 8A and 8B.
The RF generator 32 is a source of RF voltage between two electrodes.
When the generator is connected to the tissue to be ablated, current
will flow through the tissue between the active and dispersive electrodes.
The active electrode is connected to, for example the stomach tissue
(or tissue surrounding the stomach) where the ablation is to be
made, and the dispersive electrode 22 is a large-area electrode
forcing a reduction in current density in order to prevent tissue
heating. The return electrode (dispersive) (ground pad) 22, is needed
to induce resistive heating. Without it the system would look like
an open circuit, and there would not be any current flowing through
the target tissue and thus there would be no heating. As shown in
conjunction with FIG. 8B, the relatively large dispersive electrode
22 would be typically placed on the lower back of a patient, but
can be placed at other sites.
[0102] When using radiofrequency (RF) ablation, the total RF current,
IRF is a function of the applied voltage between the electrodes
connected to the tissue, and the tissue conductance. The heating
distribution is a function of the current density. The greatest
heating takes place in regions of the highest current density, J.
The mechanism of tissue heating in the RF range of hundreds of KHz
is primarily ionic. The electrical field produces a driving force
on the ions in the tissue electrolytes, causing the ions to vibrate
at the frequency of operation. The current I density J=.sigma.E,
where .sigma. is the tissue conductivity. The ionic motion and friction
heats the tissue, with a heating power per unit volume equal to
J2/.sigma.. The equilibrium temperature distribution as a function
of distance from the electrode tip, is related to the power deposition,
the thermal conductivity of the target tissue, and the heat sink
which is a function of blood circulation. The lesion size, is in
turn, a function of the volume temperature. Many theoretical models
to determine tissue ablation volume as a function of tissue type
are available. In RF ablation, lesion formation results from resistive
tissue heating at the point of contact with the RF Electrode. This
heating leads to coagulation necrosis and permanent tissue damage.
If there is poor tissue contact, RF current can not be coupled to
the underlying tissue, and the desired effect of tissue heating
is lost.
[0103] Radiofrequency ablation applies an alternating current to
tissue, in the range of 300 to 1 MHz (typically in the 500-KHz frequency
range). Unlike direct current, which creates cellular injury via
electrolytic dissociation of tissue fluids, alternating current
causes tissue damage from heat via protein denaturation, blood coagulation,
and fluid evaporation. It is similar to electrocautery but generally
less destructive because of the larger surface area of the surgical
probe, and the regulation of power delivery via probe thermistor
measurement of tissue temperature.
Mechanism of Tissue Heating
[0104] Shown in conjunction with FIGS. 9A and 9B, radiofrequency
energy heats tissue in two main ways. First, ohmic heating occurs
(FIG. 9A) on the surface by a mechanism in which the gastric tissue
in direct contact with the coil or probe acts as a resistor. This
heating falls off by the fourth power of distance from the electrode
in unipolar systems and typically penetrates only 1 mm. Second,
conductive heating occurs (depicted in FIG. 9B), in which this surface
heat is transferred to increasingly deeper tissue; conductive heating
accounts for the majority of the lesion depth.
[0105] RF can be applied either in unipolar (as was depicted in
FIGS. 9A and 9B) fashion from a tissue electrode source to grounding
pad serving as the indifferent electrode 22, or between two bipolar
tissue electrodes. Bipolar RF systems intended for surgical use
apply two linear electrodes that gently squeeze together on either
side of the gastric tissue. This creates two opposing surfaces of
ohmic heating and improves the efficiency with which the conductive
heating occurs.
Determinants of RF Lesion Size
[0106] When using RF ablation, the RF electrode temperature is
a better predictor of RF lesion size than delivered energy or current.
Monitoring of electrode temperature is typically carried out with
one or more thermistors. The maximal lesion size from conductive
heating is determined primarily by the electrode surface area and
electrode-tissue contact temperature, and is achieved at a rate
that is a reverse exponential decay with half-time of 7 to 9 seconds.
[0107] Lesion size is also influenced by time, irrigation of the
electrode, impedance rise, and convective cooling. The duration
of energy delivery has a diminishing effect on reaching maximal
lesion size after 20 seconds. Electrode irrigation results in deeper
lesions. Impedance rises with increased power, increased electrode-tissue
pressure, and repeat applications. Saline is protective against
impedance rises when compared to blood.
[0108] The Bostom Scientific/EP Technologies Cobra system (San
Jose, Calif.) is one radiofrequency system approved for commercial
use in the United States for general surgical tissue ablation, and
may be used for the methods of this invention. The electrosurgical
unit (ESU) generates a 500 kHz sine wave. This surgical probe is
a flexible single-use probe consisting of seven coagulating electrodes;
six of the seven are 12.5 mm coiled electrodes spaced 2 mm apart,
and the seventh is an 8 mm distal-tip electrode. Active coils are
selected on the ESU prior to the delivery of each lesion. Two skin
grounding pads are required to serve as indefferent electrodes.
[0109] Finite element simulation of RF ablation using these coil
electrodes shows maximal current density at the coil ends, with
2 mm extension of the 50.degree. C. tissue heat isotherm from the
coil ends. Each electrode coil contains two temperature-sensing
thermistors. One is located 1800 apart at each coil end, where resistive
heating is greatest. In vitro testing at 80.degree. C. has shown
all lesions from adjacent coils to be contiguous, although this
is only true in 75% of lesions made at 70.degree. C.
Electrode and Catheter
[0110] To deliver power more efficiently, material which has better
thermal conductivity can be chosen. It has been shown that gold,
which has four times the thermal conductivity of platinum yields
a larger lesion.
[0111] The electrode can be designed to cool the tip, thus avoiding
tissue charring. The cool-tip catheter using chilled water is one
example. Because charring can be avoided. Power can be delivered
for a longer time thus allowing the conduction to be carried deeper,
thereby increasing the lesion depth. One possible problem with the
cool-tip method is the inability to precisely determine the maximum
temperature since the maximum temperature is located beyond the
cooled electrode surface.
[0112] The electrode tip diameter has generally been increased
to obtain wider lesions and to allow cooling by nearby fluid flow,
thus creating deeper lesions as well. The larger tip diameter, however,
creates the need to control nonuniform heating and the presence
to hot spots.
[0113] Phased RF ablation allows usage of multiple electodes on
the same or different catheters. Because adjacent electrodes are
in different phases with respect to each other, an RF signal is
applied uniformly such that there will be a voltage gradient between
electrodes thus creating bipolar heating simultaneously. The advantages
of these RF methods include an increase in uniform heating and the
possibility to create long, linear lesions, which is useful for
gastric muscle lesions.
[0114] Balloon electrode RF ablation is another method for a larger
tip diameter while still having the ability to be percutaneously
inserted. It uses a semipermeable and conductive membrane, such
as gold foil, that is inflated with saline when the catheter is
inside. Dominant heating occurs at the interface of the balloon
and the tissue.
[0115] RF electrode design can also use a gel or electrolytic solution,
such as saline, instead of direct contact between the metal electrode
and the tissue. This produces a more even heat distribution in the
tissue. In the design of the electrode for soft tissue shrinkage,
the electrolytic solution is cooled to about 30 to 55.degree. C.
Not only does this electrolytic solution provide electrical conduction,
it also has a cooling effect to avoid too high a temperature at
the interface of the electrode and the tissue. Gold coating has
been used to prevent corrosion in the saline envirnment. Saline
can also be a choice for an irrigation solution because it has the
same concentration as the body's fluids, this it is not absorbed
by the body.
[0116] Having a shaft that can bend 90.degree. can be useful for
accessing the back of a joint or the mouth while a bend of 10 to
30.degree. is good for the front part of a joint compartment or
the mouth or nose.
Active Electrode Cooling RF Ablation for Obtaining Deeper Lesion
[0117] The cooling goal can be obtained with either cool water
as in the Cool-tip method or with saline. This method produces a
more uniform temperature distribution and allows a longer power
delivery thus obtaining a larger lesion without tissue desication.
Ablation Generator
[0118] FIGS. 10A and 10B describe in simplified block diagrams
the circuitry used to monitor the appropriate radiofrequency parameters.
Voltage, current, and temperature are generally measured, and all
other parameters are generated. As shown in FIG. 10A, Amplifier
A1 uses a high-impedance voltage divider to measure a fraction of
the radiofrequency voltage across the outputs. This is isolated,
converted to a root-mean-square (RMS) value, and scaled to an appropriate
level. The RMS signal has a very-low-frequency waveform and can
be easily displayed or digitized at low sampling intervals. Amplifier
A2 samples the radiofrequency current by using the current sensing
resistor, or a coil can be placed around the return. This signal
is also isolated, converted to an RMS value, and scaled. A thermistor
is used to measure temperature at the catheter tip. Amplifier A3
isolates the signal, converts the change in resistance to a linearized
voltage, and scales the output. The thermistor placement is critical
to correct temperature monitoring. This sensor is usually placed
as close to the tip as possible and thermally isolated from the
rest of the electrode. Even with these precautions, the temperature
that is monitored by the system is only an approximation of the
tissue temperature at the lesion site. The electrode temperature
that is recorded represents a complex interaction of heat generated
in the tissue interface, the radiofrequency field, and convective
heat loss to surrounding blood and tissue. Although not ideal, it
is the best system available.
[0119] The signals for power and impedance are derived from the
measured values of voltage and current. Given a sinusoidal signal
and assuming resistive loads as the major component affecting the
output, the following relationships can be used: Impdence=Voltage/current
Power=Voltage.times.Current
[0120] These associations can be generated by using analog computational
blocks as shown in FIG. 10B or by mathematically processing digitized
signals.
[0121] When a generator's output is started or terminated depends
on an interaction of the operator and automatic relationships set
by the operator or manufacturer. FIG. 11 is a simplified block diagram
of a digital control of the generator 32 output. Block A 55 represents
a set-reset flip-flop. The output goes true when the start input
is set and false when the stop input is set. This output turns on
the generator and starts the time counter. Block C 59 is the Boolean
OR function and is set true if any of its inputs are true. It serves
to sum all of the limit conditions that can stop the generator's
output. The B blocks 57 represent comparators, for which the output
goes true whenever the X input is greater than the Y input. Otherwise,
the output stays false. In this manner, the generator output is
terminated whenever the time exceeds the set time, the impedance
is outside the set minimum and maximum, the temperature is outside
the preset minimum and maximum, or the operator pushes stop
[0122] Radiofrequency generator can also operate in a power mode.
In this mode of operation, time duration is selected, limits on
impedance or temperature are set or predetermined by the manufacture,
and the desired power level is chosen. The generator outputs the
set level of power while allowing the operator to see how the impedance
and temperature levels are changing. If an adequate tip temperature
is not reached quickly, the operator can terminate the delivered
energy or adjust it. If the safety limits of the temperature or
impedance settings are exceeded, automatic shutdown occurs.
[0123] Because temperature can be crucial to the success of catheter
ablation, a temperature mode of operation has been developed. This
is also referred to the closed-loop mode of operation. The rationale
is to ensure target-tissue temperatures. Instead of the operator
choosing a set power level, a temperature set point is selected.
The generator then adjusts the power level and monitors the temperature
output. Initially, the power is limited as heating begins. The generator
then delivers a much larger output level. Usually the maximum, as
long as the difference between the set point and the monitored value
is larger (10.degree. to 12.degree. C.) than a manufacturer's determined
level. After that difference is at or below the manufacturer's setting,
power drops off. When the temperature difference becomes sufficiently
small (2.degree. to 3.degree. C.), a minimal amount of power is
delivered to maintain temperature and to allow monitoring of other
parameters. The generators typically cease to deliver power if any
of the safety limits are exceeded.
Microwave Ablation
[0124] In the method and system of this invention, microwave energy
may be delivered through a probe or catheter antenna to the affected
gastric or surrounding tissue which allows the procedure to be performed
percutaneously or endoscopically. In microwave ablation, the frequencies
915 MHz and 2.45 GHz are usually used due to Federal Communications
Commission (FCC) restrictions.
[0125] Unlike RF which generate lesions of relatively limited size
and penetration, microwave energy usually allows for greater tissue
penetration, and thus a greater volume of heating. Table two below
compares some features of RF vs. microwave ablation. TABLE-US-00002
TABLE TWO Comparison of RF vs. Microwave Radiofrequency Microwave
Waveform Continuous N/A Unmodulated sinusoidal Frequency 300-1,000
kHz 915, 2,450 MHz Voltage V <100 V N/A Mechanism of injury Resistive
heating Radiant heating Lesion size Small Unknown Control of injury
High High
[0126] In microwave ablation, a lesion is created as heat conducts
passively away from this zone and the surrounding myocardium is
heated to a temperature where cell death occurs (approx. 50.degree.
C.). Lesion size is therefore a function of the size of the electrode
and the resulting temperature at the electrode tissue interface.
[0127] The mechanism of thermal injury in microwave ablation is
dielectric heating. Body tissue contains various polar molecules,
of which water is the most abundant and has an exceptionally high
polarity. At microwave frequencies, electromagnetic radiation causes
rotation of molecular dipoles; heat is created as these movements
are opposed by intermolecular bonds and thus represents dissipation
of the part of the energy of the electromagnetic field in the form
of molecular friction. Energy absorption is affected by the presence
of electrolytes and other polar molecules such as amino acids in
tissue water. Conductive heating is a comparatively minor contributor
to tissue heating. Heat is produced by the mechanical friction between
the water molecules and surrounding structures.
[0128] Microwave hyperthermia has shown to be useful in radiation
oncology for the treatment of various solid tumors. Also, because
of its experience in enlarging myocardial lesions in catheter ablation,
microwave energy would be useful in gastric ablation. Microwave
energy is delivered down the length of a coaxial cable that terminates
in an antenna capable of radiating the energy into tissue. Radiant
energy causes the water molecules in myocardial tissue to oscillate,
producing tissue heating and cell death. The higher frequency of
microwave energy allows for greater tissue penetration and theoretically
a greater volume of heating than that possible with RF, which produces
direct ohmic or resistive heating.
[0129] Microwave energy for tissue ablation effects has been studied
using a helical antenna mounted on a coaxial cable (2.44 mm o.d.).
High-frequency current at 2,450 MHz was delivered via the helical
antenna into a tissue-equivalent phantom model. The temperature
distribution profile was measured around the antenna as well as
into surrounding volume (the depth of penetration). The volume of
heating for the microwave catheter system was 11 times greater than
that of an RF electrode catheter at the same surface temperature.
In addition, the microwave catheter penetrated an area that was
twice as large as that penetrated by the RF catheter. These data
suggest microwave energy will produce larger lesion than RF because
a greater volume of tissue is being heated, this is advantageous
for gastric ablations. An additional theoretical advantage of the
microwave system is that direct tissue contact is not crucial for
tissue heating since heating occurs via radiation, and not via direct
ohmic heating as seen with RF.
[0130] Helical and whip antenna designs have also been evaluated
in a tissue-equivalent phantom at 915 MHz and 2,450 MHz utilizing
a coaxial cable (0.06 in o.d.). All catheters were measured utilizing
a network analyzer prior to placing them in the phantom model. Such
analysis demonstrated the great variability in tuning of these microwave
catheters.
Microwave Ablation
[0131] In general, higher water content (HWC) means higher dielectic
loss and HWC tissues will absorb more energy. Low water content
(LWC) tissues, such as fat or bone, have dielectric constants and
conductivities about one order of magnitude smaller that high water
content (HWC) tissues, such as muscle or organs.
[0132] Many of the benefits of microwave ablation relate specifically
to its mode of heating. Heating occurs in volume and relies very
little on thermal flow, allowing microwaves to ablate areas near
high blood flow. This is a distinct advantage over RF ablation.
Because of the volume heating effect, charring may be eliminated
and simply increasing the applied power will also increase lesion
size. Power deposition falls as a function of 1/r.sup.3 in microwave
ablation (as opposed to 1/r.sup.4 in RF) so power will theoretically
travel farther and more uniformly into the tissue. Serious complications
apparent in other ablation modalities have not been seen in microwave
ablation. Antennas need only be a few centimeters long, reducing
the invasiveness of the procedure. Arrays of probes may be employed
to increase lesion size or uniformity. In addition, the probe or
catheter antennas may be easily sterilized and reused, reducing
procedure costs.
Microwave Generator
[0133] Tissue-ablation microwave generators typically generate
the electromagnetic field using a magnetron, such as is used in
microwave ovens. The microwave generator provides the necessary
microwave power to be delivered to the antenna. Several methods
to create this power are available. In general, there are two subcomponents
to the generator: a power supply and a microwave source. The power
supply converts the line poser (typically 120 VAC, 60 Hz) to a suitable
supply for the microwave source. The microwave source then converts
the electrical power to microwave power. Shown in conjunction with
FIG. 12 is a simplified block diagram of a microwave system, comprising
a microwave source 356, coupling network 360, power supply 366,
and the catheter antenna 362.
[0134] The most common microwave source used in ablation systems
is a magnetron due to its low cost, high power output (often several
MW), and high conversion efficiency (>80%). The magnetron is
a crossed-field resonant cavity tube that converts electron motion
to microwave poser. The magnetron filament is heated with a high
current (3.3 V, 10 A typical) until thermionic emission causes electrons
to "boil" off similar to water molecules boiling off as
steam. The high negative potential between the cathode and anode
(4 kV typical) creates a large electric field that accelerates the
electrons toward the anode. As they accelerate, the axial magnetic
field exerts a force on the electrons in a direction perpendicular
to their original motion; that is, it pushes the electrons azimuthally
around the cathode.
[0135] The electric and magnetic field strengths are usually set
so that the curving path of an electron just skims the face of the
anode block. In this way, the electrons interact with the resonant
cavities to set up EM fields. Hence, energy is transferred from
the electron motion to the EM fields inside the cavities. Each cavity
resonates at the design frequency (2.45 GHz, for example) and a
loop is placed inside one of the cavities to extract the microwave
power.
[0136] The AFx system (AFx, Inc., Freemont, Calif.) is one currently
available microwave system available for cardiac tissue ablation.
This system may also be adapted to be used for gastric ablations.
The system consists of a magnetron-powered 2.45 GHz generator with
power and timer settings, and a hand-held surgical probe that has
an antenna at the end through which the electromagnetic radiation
is emitted. The Flex-2 is a surgical probe with a 2 cm rigid antenna.
The Flex-4 probe has both a bendable shaft and a 4 cm flexible antenna.
The antennas have the desirable feature of being shielded on one
side. This ensures that only one side of the antenna delivers the
ablation energy, an advantage for epigastric ablations.
High Intensity Focused Ultrasound (HIFU) Ablation
[0137] In one aspect of the invention, ablations may be performed
using high intensity focused ultrasound (HIFU). When high-intensity
ultrasound waves are focused at targets deep within the human body,
the temperature in the region of focus can be increased to a level
high enough to kill the cells in that region.
[0138] Ultrasound has several characteristics which make it well
suited for the induction of thermal therapy. These include the feasibility
of constructing applicators of virtually any shape and size, and
good penetration of ultrasound at frequencies where the wavelengths
are on the order of millimeters. The small wavelengths allow the
beams to be focused and controlled. Clinical research has shown
that ultrasound beams can penetrate deep and that the power deposition
pattern can be controlled.
[0139] Ultrasound is a form of mechanical energy that is unique
among available medical radiation methods in that it can be sharply
focused within the tissue. The usual frequency range of medical
ultrasound used for imaging and surgical application is 0.5 MHz
to 20 MHz. For this range, it has a low absorption rate in soft
body tissue and a relatively short wavelength. While the absorption
rate limits how deeply the wave can travel inside of the body, the
wavelength governs how precisely the wave can be focused onto the
tissue. Hence, ultrasonic energy can be deposited deep inside the
body with precise focus. As the ultrasound pressure wave travels
through the body it loses energy due to scattering and absorption.
Scattered energy is used for imaging while energy absorption causes
tissue heating.
[0140] Shown in conjunction with FIG. 13, is the basic principle
of the ultrasonic ablation technique which is referred to synonymously
as focused ultrasound surgery (FUS) or high-intensity focused ultrasound
(HIFU). In this technique, a high-intensity ultrasound beam is brought
to a tight focus within the target tissue volume, which may lie
deep within the body. The beam passes through the overlying skin
and other tissues without harming them. The absorption reaches a
maximum in the focal volume where the intensity is at its highest.
The temperature at the focal volume is raised to 56.degree. C. and
held there for 1 to 3 seconds, which kills the cells in focus. There
is a very sharp boundary between dead and live cells at the border
of the focal volume. Also shown in FIG. 13, the source is a planar
ultrasound transducer with diameter D and is situated outside of
the body. The ultrasound beam is focused at the desired depth inside
of the body by a focusing lens. The lesion produced has length l
and width w and is ellipsoid or cigar shaped.
Heating Mechanisms and Biological Effects
[0141] HIFU produces an effect on tissues by several mechanisms:
thermal effects, cavitation, other mechanical forces, and chemical
reactions and acceleration. Thermal and cavitation mechanisms are
the most important and best understood. Thermal heating is caused
by absorption of ultrasonic energy by the tissues. This leads to
a rise in temperature of the tissues. Consequently, the rise in
temperature is dependent on the intensity of the ultrasound beam
and the heat absorption coefficient of the tissue. In HIFU, the
ultrasonic intensity at the beam focus is much higher than that
outside of the focus. The ultrasonic focus can easily generate temperature
elevation of 30.degree. C. to 40.degree. C., coagulating tissue
in just a few seconds.
Ultrasonic Ablation System
[0142] A complete HIFU system would normally consist of an ultrasonic
applicator, electromechanical components for steering and positioning
the acoustic beam, a display for therapy planning and imaging, and
a computer for HIFU dosage calculations and control, as well as,
for monitoring feedback during ablation.
[0143] Shown in conjunction with FIG. 14 is a simplified block
diagram of an ultrasound system for hyperthermia induction. The
RF signal is generated by a signal generator 74 or an oscillator
and is amplified by an RF amplifier 76. The generation of the RF
signals to be converated into mechanical motion is in principle
similar in all systems. The forward and reflected electrical power
are measured after amplification in order to obtain the total acoustic
power output. The signal enters the transducer through a matching
and tuning 80 network that couples the electrical impedance of the
transducer 82 to the output impedance of the power amplifier 76.
The power output is controlled by the amplitude and duty cycle of
the RF voltage.
[0144] Shown in conjunction with FIG. 15 is a general structure
of a high-power ultrasound transducer. The thickness of the plate
of piezoelectric material 83 determines the operating frequency.
Both surfaces of the transducer are covered by thin metal electrodes
85. The transducer plate is mounted on the holder in such a way
that it has maximum freedom to move. On the front surface there
can be a one-quarter wavelength matching layer 87 that reduces the
acoustic mismatch between the transducer and the coupling media.
However, it is optional and adequate power outputs can be obtained
without it. An air space behind the plate provides a low impedance
backing. This space can also house the electrical matching circuit
80. Maximum electrical efficiency of the transducer can be obtained
when the transducer is matched to the electrical impedance of the
driving amplifier and the electrical and mechanical resonances of
the transducer are tuned together.
[0145] Piezoelectric materials lack a center of symmetry in their
lattice structure, and have the property that the application of
pressure causes an electrical voltage to appear across the crystal.
The voltage is proportional to the applied pressure within the elastic
limits of the material. By applying a changing voltage across a
piezoelectric crystal, electrical energy can also be converted to
mechanical thickness change of the crystal. As is known in the art,
since hyperthermia transducers capable of producing high power,
single-frequency continuous waves for extensive periods are needed,
lead zirconate titante (PZT) is generally used. Also in reference
to FIG. 15, the maximum stress wave is obtained when the thickness
of the plate d=.lamda./2 or an odd multiple of .lamda./2. The frequency
which corresponds to the half wavelength thickness is the fundamental
resonant frequency of the transducer.
[0146] For the application of the current invention, the piezoelectric
ceramic can be manufactured in the shape of a cylinder with electrodes
on both inner and outer surfaces. When an RF voltage is applied
on the electrodes, the cylinder wall thickness will expand and contract
with the voltage. This generates a cylindrical ultrasound wave which
propagates radially outward. Cylindrical applicators are known in
the art for delivering for prostate applications, and can be similarly
used for gastrointestinal (GI) applications of the current invention.
One such four-element intracavitary applicator is shown in conjunction
with FIG. 16. As will be clear to one of ordinary skill in the art,
these can be adapted for the various gastric applications.
Cryoablation
[0147] Cryoablation generally is a surgical technique that employs
freezing to kill the target cells. The target tissue is frozen to
a lethal temperature dependent on the tissue type to generate an
ice ball. Accurate monitoring of the ice ball margin and temperature
is achieved by employing intraoperative ultrasound and placing thermocouples
inside of the cryoprobe.
[0148] The mechanism of tissue injury in cryoablation are not fully
understood and there are some controversies about then. Generally,
two mechanisms are considered as the main causes of direct cellular
injury: (1) cell dehydration by osmosis when the ice ball is created
in the extracellular space, and (2) intracellular ice formation
at a high cooling rate.
[0149] At slow rates of cooling, tissues tend to freeze extracellularly.
Slow cooling rates encourage the crystals to expand to a very large
size. When these crystals develop in the extracellular space, migration
of water out of the cells occurs because of the pressure gradients
induced by the combined influence of concentration differences and
capillarity. The ultimate end of such a process is dehydration of
the cells and the development of external ice crystals which can
be many times the size of individual cells.
[0150] At high cooling rate, the migration of water out of the
cells may become inadequate to support the rapid growth of extracellular
crystals. As a consequence, intracellular ice formation occurs,
probably from growth of external ice through minute water-filled
pores in the cell membrane. Intracellular ice crystals will tear
down the membranes of cells and organelles inside the cell.
Cryogen
[0151] Liquid nitrogen and argon are widely used as cryogens. The
boiling temperatures of LN.sub.2 and argon are -196.degree. C. and
-186.degree. C., respectively. However, this low temperature is
hard to attain in the probe design. One reason is back pressure,
which limits the flow of cryogen into the cryoprobe, and the other
reason is Liedenfrost boiling.
Cryoprobe
[0152] The LN.sub.2 probe generally consists of a closed-end tube
with two tubes concentrically arranged within it. Shown in conjunction
with FIG. 17, is the basic design for a typical LN.sub.2-based cryoprobe.
Inside the probe, there is a funnel 118 for liquid nitrogen to go
through. At the end of funnel, it hits the warm uninsulated tip
of the cryoprobe where it changes phase, expanding 700 times in
volume. The expanding gas exits the cryoprobe around the supply
tube. This gas expansion is the constraint on the probe's functioning
since it creates a back pressure that limits the flow of liquid
nitrogen into the cryoprobe. Another phenomenon, caused by phase
change, is the Liedenfrost boiling. When liquid nitrogen expands,
gas bubbles form between the liquid and the metal, acting as an
insulator. As a result, the temperature of the cryoprobe tip is
about -160.degree. C., not -196.degree. C. The rate of complications
and adverse effects are significantly higher with LN.sub.2-based
systems due to a slow response time to control adjustment.
[0153] Shown in conjunction with FIG. 18 is an argon-based cryoprobe
available from Endocare Inc., in which the system operation is based
on the Joule-Thomson principle. Such a system can also be adapted
for gastric ablation. In this system when a gas flows from a region
of higher pressure to a region of lower pressure through a constricted
passage (J-T port), it is said to be throttled. Based on Joule and
Kelvin's principles, we know that most gases drop in temperature
when throttled. For some gases, notably hydrogen and helium, the
temperature rises. Whether there is a rise or fall in temperature
depends on the particular range of pressures and temperatures over
which the change occurs. For each gas, there are different values
of pressure and temperature at which no temperature change occurs
during a Joule-Thomson expansion. That temperature is the inversion
temperature. The ratio of the observed drop in temperature to the
drop in pressure-is-the-Joule-Thomson coefficient (dT/dP). The temperature
of a particular gas increases or decreases after going through a
J-T port depending on whether its original temperature is above
or below its maximum inversion temperature. Generally, the temperature
decreases as long as the maximum inversion temperature is above
ambient temperature and vice versa.
[0154] FIG. 18(b) shows a different type of cryoprobe available
from Galil Medical Ltd. The details of these systems are disclosed
in U.S. Pat. No. 5,800,787 (a) and U.S. Pat. No. 6,142,991 (b),
which are incorporated herein by reference.
Laser Ablation
[0155] Lasers are widely used in ablations and many other medical
applications, and can be adapted for use with gastric or other gastrointestinal
(GI) ablations of the current invention. Lasers are coherent, and
the energy of a laser beam is concentrated in a very narrow wavelength
band. All photons in a laser beam are exactly in the same phase.
Lasers are always directional. The direction of a laser beam is
exactly parallel to the axis of the laser generator cavity. Lasers
have these properties because of the way lasers are generated
[0156] A typical laser ablation system is shown in conjunction
with FIG. 19. The system consists of a solid state laser generator
128 with control system, an optical fiber cable 130, a laser probe
126, a water cooling system 132, and an external foot switch 134.
Laser Tissue Ablation
[0157] With laser ablation, tissues are ablated through tissue
coagulation, water vaporization, tissue dehydration, tissue cabonization
and pyrolysis. Ablated tissue can be directly removed through vaporization
and explosive mechanical ruptures.
Laser System
[0158] Lasers are generated inside laser generator resonate cavities.
The lasing medium could be a gas, dye, solid state crystal, or semiconductor.
The excitation mechanism converts the electric power from the power
supply unit to other types of energy to excite the lasing medium.
After the lasing medium is excited, its molecules are energized
from their low energy levels to their higher energy levels, which
is the inverted population state. The lasing medium in its inverted
population state emits free photons when its molecules transit from
their higher energy levels back to their low energy levels. When
free photons travel in the lasing medium and pass by other excited
molecules, the excited molecules are stimulated to transit from
their higher energy levels to their lower energy levels causing
them to emit photons of the same frequency, phase, and direction
as the free photons. This is the phenomenon of stimulated emission.
Free photons are amplified by the stimulated emission effect in
the laser generator cavity in all directions. Most of them will
quickly exit from the cavity if they are not moving in a direction
exactly parallel to the axis of the lasing cavity, and will be reflected
back and forth between the high reflector and the output coupler,
which is in fact, a partial reflector. Photons in the cavity-axis
direction are reflected between the two reflectors. They are amplified
by the stimulated emission effect of the excited lasing medium.
Amplified photons form the unique phased and unidirectional output
laser beam.
[0159] Compared to the complete reflector at one end of the cavity,
the output coupler at the other end is actually a partial reflector.
It lets the amplified laser photons partially exit from the laser
cavity to become the output laser beam. The majority of the laser
photons remain in the cavity to be further amplified by the excited
lasing medium. The output coupler is usually connected with other
optical delivery devices such as an optical fiber cable, which will
conduct the output laser beam to the tissue where the laser beam
will be applied.
[0160] The excitation mechanism excites the lasing medium and keeps
it at its inverted population state. The excited lasing medium amplifies
the laser beam in the cavity through the stimulation emission effect.
The whole laser cavity is a balanced laser system as the electric
power is taken from the power supply unit and converted to the output
laser energy by the excitation mechanism and the lasing medium.
[0161] FIG. 20 shows a schematic diagram of a working laser generator,
which can be adapted for gastric ablation application. The excitation
mechanism is powered by the electric power supply unit and excites
the lasing medium. Photons are amplified by the excited lasing medium
and resonate between the high reflector and the output coupler.
The output coupler releases a certain amount of laser photons to
form the output laser beam.
Laser Ablation Systems
[0162] As shown in conjunction with FIG. 21, laser ablation systems
usually consist of laser generator 128, computerized control systems
135, optical conductive units including optical fiber cables 130,
laser probes 126. Lasers are generated by laser generators 128,
which are controlled by their control systems 135. Output laser
beams are coupled into optical delivery systems or optical fiber
130 cables and conducted to the laser probes 126. The laser probes
then apply the laser beams to target tissues 54.
Control Systems
[0163] Control systems usually vary among different laser ablation
systems. They are essential in controlling laser ablation procedures.
Shown in conjunction with FIG. 22 is a generic control system. The
microcomputer 142 with control algorithm is the center. The control
center integrates inputs from different sensors and manual control
settings, calculates optimized parameters by using these inputs
according to preprogrammed control algorithms, and controls its
effectors on the laser generator--the reflectors and the excitation
mechanism. The generic control system shown in FIG. 22 can control
laser output, pulse duration, and pulse frequencies by controlling
the piezoelectic transducer 138, and it can control the laser output
140 pulse power densities by controlling the pumping mechanism.
[0164] The cooling systems effectively remove the heat which is
generated when laser radiation energies are absorbed by target tissues.
They reduce the amount of heat transferred to adjacent tissues,
minimize the damage to the adjacent tissures, and improve the precision
of ablation procedures. Both air spraying and water spraying are
used as cooling mechanisms.
[0165] As is well known in the art, these systems can be adapted
for gastric or other gastrointestinal (GI) tract ablations of the
current invention.
Gastrointestinal (GI) Ablations
[0166] Shown in conjunction with FIG. 23 the gastrointestinal (GI)
tract runs from the mouth to the anus and includes the esophagus,
stomach, small bower or intestine, and the large bowel (colon) and
rectum. The liver is also widely considered as a gastrointestinal
organ.
[0167] In one object of the invention, the ablations may be performed
as adjunct therapy for selected gastrointestinal abnormalities such
as polyps, tumors, and cancers of the digestive system; specifically,
the esophagus, stomach, liver, biliary tact, pancreas, colon, rectum,
and anus.
Liver Ablations in Stomach Cancer
[0168] Frequently in stomach cancer, the disease has already spread
to the lymph system by the time of diagnosis. In such a case, the
most common treatment is surgery by which cancer and surrounding
stomach are removed. Cryoablation, and radiofrequency ablation,
and/or standard liver resection may be performed at the time of
stomach resection, depending on physician judgement.
Ablation Therapies for Hepatic Colorectal Carcinoma Metastases
[0169] Although hepatic resection remains the gold standard for
the treatment of live tumors, a large number of patients are not
ammenable to surgical therapy. This may be due to unfavorable anatomy,
the presence of multiple tumors, or poor hepatic reserve. Cryoablation,
RF ablation, and laser ablation may be applied for the ablation
of liver tumors.
Hepatic Tumor Ablations
[0170] Hepatic cancer is one of the most common malignancies. It
has two primary types: hepatocellular carcinoma (tumor starts in
the liver) and metastatic (tumor originates elsewhere and spreads
to the liver). A majority of patients are not amenable to hepatic
resection surgery due to the size, location, and number of tumors.
Several ablative techniques are used instead.
[0171] For patients with one to three small tumors located near
the surface of the liver, laparoscopic or percutaneous RF treatments
yield good results. Using ultrasonic guidance, a needle probe is
inserted through the skin and into the tumor. The tip of the probe
opens to expose an umbrella shaped array of hook electrodes once
on site. RF power is applied for 5 to 15 min, and the current design
is capable of producing lesions approximately 3 cm in diameter.
The major factor limiting the lesion size comes from hepatic perfusion.
By performing this minimally invasive surgery, fewer patients suffer
from side effects, such as infection, bile leakage, or breathing
difficulties, and most reoccurrences of cancer are along the outer
edges of tumors that are too large to be completely destroyed.
[0172] RF ablation during an open operation is more suitable for
patients with numerous, larger tumors, or tumors located near large
blood vessels. More accurate placement of the probe can be achieved
in open surgery, therefore increasing the attainable lesion size.
Some side effects, such as bleeding of the parenchymal cells, can
be avoided as well. Compared with other ablative technologies, particularly
cryablation, RF ablation yields a relatively low complication rate
and a lower overall mortality. It has the worst performance when
applied to tumors located near blood vessels since the nearby blood
flow significantly convects away the heat. Other disadvantages include
long procedure time and difficulty in ultrasonic imaging of the
lesion.
Localized Gastrointestinal Carcinoid Tumor
[0173] In one aspect, if the regional disease is found to be unresectable,
palliative surgery such as cryoablation or RF ablation may be performed.
Treatment is customized for each patient depending on the growth
of the tumor and/or symptoms.
Tissue Ablation--Obesity
[0174] Shown in conjunction with FIGS. 24 and 25 are sites marked
where ablations may be performed as a treatment for obesity or to
induce weight loss. As was previously mentioned, the ablations may
be approached from the epigastric side via laproscopic surgery,
or may be approached via the mouth and esophagus in an anesthetized
patient, and be performed endogastrically. Also, as previously mentioned
the ablations may be performed using radiofrequency catheter ablation,
radiofrequency catheter ablation using irrigated tip catheter, microwave
ablation, high intensity focused ultrasound (HIFU) ablation, cryoablation,
or laser ablation.
Disruption of Pacemaker Region of the Stomach
[0175] Various mechanisms which disrupt the normal physiology of
stomach and the associated nervous system may be targeted for ablation,
whereby disrupting the normal function which leads to weight loss.
For example, ablating the pacemaker region of the stomach can slow
normal electrical activity of stomach.
[0176] Under normal circumstances, the pacesetter cells, which
are smooth muscle cells that are capable of rhythmic, autonomous,
partial depolariztion, are located in the upper fundus 15 region
of the stomach. These cells generate slow-wave potentials that sweep
down the length of the stomach toward the pyloric sphincter at a
rate of approximately three per minute. Depending on the level of
excitability in the smooth muscle, they may initiate contractions
recognized as peristaltic waves that sweep over the stomach in pace
with the basic electrical rhythm (BER) at a rate of 3/minute. By
ablating at and around the pacemaker region, the intent is to decrease
basic electrical rhythm (BER), whereby the stomach empties less
efficiently, which leads to a feeling of "fullness", and
the patient's do not feel hungry. As shown with reference to FIG.
24, the ablation around the pacemaker zone 25 may be from the inside,
or outside of the stomach, or both.
[0177] Applicant's patent application Ser. No. 11/047,233 and Ser.
No. 11/032,298 disclose accomplishing a similar function by stimulating
the gastric muscle. The advantage of ablation is that no hardware
component needs to be left in the body. Another advantage of ablation
is that it may offer a more permanent solution, without concern
for battery status of an implantable device.
Ablation of Gastric Muscle
[0178] In another object of the invention, the ablation lesions
may be performed with the intent of disrupting the muscle layers
of gastric wall. In this disclosure, the terms stomach, stomach
muscle, gastric wall, and gastric wall muscle are used interchangeably.
Shown in conjunction with FIG. 24, are 3 layers of stomach, which
are the longitudinal layer 14, the circular layer 16, and the oblique
layer 18. As shown in conjunction with FIGS. 24 and 25 ablation
may be performed at various regions of the stomach. In FIG. 24,
sites 152, 153, 154, and 155 are just some examples. The ablation
lesion may be performed in clusters or individual lesions may be
connected to form lines, or a combination of lines and clusters.
In this aspect, even though the basic electrical rhythm (number
of contractions) does not change, the contractility of the gastric
muscle does become less efficient, which leads to longer times for
the stomach to empty, thereby generally providing a feeling of fullness,
and the patient feeling less hungry or not hungry.
Ablation of Endogastric Lining--for Cells that Produce the Hunger
Hormone Ghrelin
[0179] In another object of the invention, ablation may be performed
to damage the mucosal cells lining the stomach that secrete the
hormone ghrelin. The hormone ghrelin has been termed the appetite
hormone. As shown in conjunction with FIG. 26, the levels of ghrelin
typically have peaks which correspond to breakfast, lunch, and dinner,
labeled B, L, and D respectively. The rationale for the ablation
is that by ablating the mucosal cells, the plasma levels of ghrelin
will decrease, leading to appetite suppression and weight loss.
Disruption of Enteric Nervous System
[0180] In another object of the invention, ablation is performed
for disruption of parts of the enteric nervous system. This is also
shown in conjunction with FIGS. 24 and 25. In FIG. 24, ablation
sites marked as 152, 153, 154 and 156 will also disrupt the functioning
of the enteric nervous system, when the lesions are deep enough
in the muscle. This can be approached from the endogastric side
or epigastric side.
[0181] The stomach is richly innervated by extrinsic nerves and
by the neurons of the enteric nervous system. Axons from the cells
of the intramural plexus innervate smooth muscle and secretory cells.
Parasympathetic innervation to the stomach is also supplied by the
vagus nerves, while sympathetic innervation to the stomach is provided
by the celiac plexus. In general, parasympathetic nerves stimulate
gastric smooth muscle motility and gastric secretions, whereas sympathetic
activity inhibits these function. Numerous sensory afferent fibers
leave the stomach in the vagus nerves; some of these fibers travel
with sympathetic nerves. Other sensory neurons are the afferent
links between sensory receptors and the intramural plexuses of the
stomach. Some of these afferent fibers relay information intragastric
pressure, gastric distention, intragastric pH, or pain.
[0182] By disrupting the enteric nervous system, the functioning
of stomach is made less efficient. This will also lead to inefficient
emptying of the stomach, and a general feeling of fullness. In other
words, the patient will not feel as hungry
Vagal Nerve(s) Disruption
[0183] In one object of the invention, the ablation may be targeted
to vagal nerve(s) disruption. Again, this may be done from the endogastric
side (via mouth and esophagus) or from the epigastric side. Shown
in conjunction with FIG. 24, these area's are labeled 150 around
the esophagus, and 154 on the stomach diagram. As one example, without
limitation, a probe connected to high intensity focused ultrasound
(HIFU) source may be placed in the distal end of the esophagus,
close to lower esophageal sphincter (LES), and ablation of vagal
nerve(s) may be performed through the esophagus. Alternatively,
microwave energy source may be used, and the site marked 154 which
is around the lesser curvature of the stomach may be targeted. Clinical
studies have confirmed that surgical vagotomy promotes weight loss.
Ablation for Gastroesophageal Reflex Disease (GERD)
[0184] The methods and system disclosed, may also find use in gastroesophageal
reflux disease (GERD). GERD results from the chronic backward flow
of stomach contents into the esophagus. The acid, bile, and digestive
enzymes cause irritation of the esophagus and symptoms of heartburn,
regurgitation, chest pain, voice disorders, and swallowing problems.
[0185] Normally, the muscular valve (lower esophageal sphincter
or LES) at the junction of the esophagus and stomach prevents reflux
from occurring. Reflux of stomach contents occurs when the LES and
diaphragm are unable to provide enough tone or force to squeeze
adequately on the esophagus. This may happen in some patients in
whom the muscles have weakened over time or in those patients with
hiatal hernias. The barrier function in these patients is completely
lost, and reflux is present throughout the day.
[0186] The majority of patients with GERD, however, have normal
LES and diaphragm pressures, yet the sphincter muscles relax frequently
throughout the daytime to cause reflux. The relaxation events permit
excessive reflux of stomach contents and the patient develops significant
symptoms of GERD.
[0187] This abnormal event is a neurological reflex, which is the
transient lower esophageal relaxation (tLESR) and is the cause of
GERD in over 80% of patients. A tLESR is prompted when there is
stretching of the stomach wall, as after a meal. The stretch receptors
generate a nerve impulse, which travels upward within the myenteric
plexus of the gastroesophageal junction. The myenteric plexus is
a network of very small nerves lying between the layers of the stomach
and esophagus musculature. The impulses travel through the LES,
into the esophagus, and then join the vagus nerve on their way to
the brain. When the brain receives these signals, a motor signal
is sent to the LES causing prolonged relaxation.
[0188] The importance of tLESR in the development of GERD has been
extensively investigated. Clinical investigations have also focused
on the delivery of radiofrequency energy for the treatment of GERD.
[0189] Investigators at Stanford University have recently performed
radiofrequency ablation of the stomach cardia in Yucatan mini-pigs
to establish the effect on these nerve pathways. These nerve fibers
course between the muscle layers of the LES and cardia. The effect
of delivering radiofrequency energy to the cardia on the parameter
of gastric yield pressure has been shown. This test is directly
related to tLESRs. The stomach is stretched with carbon dioxide
gas until the LES yields or relaxes in response to pressure. Yield
pressures were higher in all animals after treatment, indicating
that the nerve reflex arc was modulated to have a higher threshold
for stimulation, or a lower frequency of transmission to the brain.
[0190] In one preferred embodiment, ablation therapy is performed
for treating reflux disease, as is shown in conjunction with FIGS.
27A and 27B. As depicted in FIG. 27A, a catheter utilizing a balloon,
may be used. Shown in conjunction with FIGS. 27A and 27B, the balloon
may be deflated or inflated.
[0191] Shown in conjunction with FIGS. 28A, 28B, and 28C, the physician
positions the catheter, inflates the balloon, deploys the needles
and begins irrigation, During treatment, radiofrequency energy is
delivered in a controlled manner to the tissue surrounding the needle
electrodes (FIG. 28A). The treatment sequence is repeated to create
well-defined coagulative lesions along the length of the lower esophageal
sphincter and cardia (FIG. 28B). Over the next few weeks, the coagulated
tissue resorbs and shrinks, increasing resistance to reflux (FIG.
28C).
[0192] Many embodiments of the invention have been described. Various
modifications may be made without departing from the scope of the
claims. It is therefore desired that the present embodiment be considered
in all aspects as illustrative and not restrictive, reference being
made to the appended claims rather than to the foregoing description
to indicate the scope of the invention.
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