U.S. patent number RE32,057 [Application Number 06/393,628] was granted by the patent office on 1985-12-31 for radio frequency treatment of tumors while inducing hypotension.
Invention is credited to Harry H. LeVeen.
United States Patent |
RE32,057 |
LeVeen |
December 31, 1985 |
Radio frequency treatment of tumors while inducing hypotension
Abstract
The method of treating tumors by radio frequency heating at the
location of the tumor to cause necrosis of the tumor tissue in
which hypotension is induced during the treatment.
Inventors: |
LeVeen; Harry H. (Charleston,
SC) |
Family
ID: |
38442576 |
Appl.
No.: |
06/393,628 |
Filed: |
June 30, 1982 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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643661 |
Dec 23, 1975 |
3991770 |
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595094 |
Jul 11, 1975 |
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436102 |
Jan 24, 1974 |
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Reissue of: |
741043 |
Nov 11, 1976 |
04119102 |
Oct 10, 1978 |
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Current U.S.
Class: |
607/99;
607/154 |
Current CPC
Class: |
A61N
1/403 (20130101); A61N 1/06 (20130101) |
Current International
Class: |
A61N
1/06 (20060101); A61N 1/40 (20060101); A61N
001/40 () |
Field of
Search: |
;128/804,422,399,1.3-1.5 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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1284528 |
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Dec 1968 |
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DE |
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2356183 |
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Oct 1974 |
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DE |
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353231 |
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Jul 1931 |
|
GB |
|
618179 |
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Feb 1949 |
|
GB |
|
Other References
Urbach, "The Blood Supply of Tumors," Advances in Bio. of the Skin,
vol. 2, 1961, pp. 123-149. .
Yocom, Jr., "The Treatment . . . X-Ray", Fischer's Mag., Jan. 1925,
6 pages. .
Geyser, "Diathermic . . . Cancer," Jan. 1925, Fischer's Magazine.
.
Warren, "Preliminary Study . . . Tumor Cases", The Am. J. of
Roentgen & Radium Therapy, vol. 33, No. 1, Jan. 1935, pp.
75-87. .
Muckle et al., "The Sel. Inhibitory . . . Malignant Cells", Brit.
J. Cancer, vol. 25, No. 4, pp. 771-778. .
Goldenberg et al., "Direct & Abscopal . . . Hyperthermia",
Zeitschrift fur Natur. For., 8, 26, 1971, pp. 359-361. .
Gessler et al., "Eradication of Spon. Mouse Tumors . . . ", Exp.
Med. & Surg., vol. 8, pp. 143-167, 1950. .
Geyser, "Diathermia: A Physiological Specific", N.Y. Med. Journal,
pp. 354-357, 2/1916. .
Geyser, "What Diathermia Will . . . Growths," The J. Med. Council
of Phil., Apr. 1917. .
Geyser, "Surgery, Roentgen Ray or Diathermia", The Int. J. Surgery,
Jan. 1919. .
Geyser, "Non-Surgical Treatment of Cancer", N.Y. Med. Journal, Feb.
2, 1918. .
Geyser, "Diathermia in the Phys. . . . ", JAA Med. Phys. Research,
Mar. 15, 1924, pp. 153-156. .
Guy et al., "Therapeutic Application . . . Power", Proceedings of
IEEE, vol. 62, No. 1, pp. 55-75, Jan. 1974. .
Guy, "Analyses . . . Phantom Models", Proceedings of IEEE, 1970.
.
Cater et al., "Combined Therapy . . . Rat Hepatone", Acta
Radiological Therapy Physics Biology, vol. 2, pp. 321-336, 10/1964.
.
Crile, "Selective Destruction of Cancer . . . ", Annals of Surgery,
vol. 156, No. 3, Sep. 1962. .
Overgaard et al., "Shortwave Treatment . . . Carcinoma", European
J. Cancer, vol. 8, pp. 65-78, 1972. .
Nakamura et al., "An Experimental Study . . . ", 1936..
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Primary Examiner: Cohen; Lee S.
Attorney, Agent or Firm: Gipple & Hale
Parent Case Text
RELATED CASES
This application is a division of LeVeen Application Ser. No.
643,661, filed Dec. 23, 1975, now U.S. Pat. No. 3,991,770.
Application Ser. No. 643,661, is, in turn, a continuation-in-part
of LeVeen application Ser. No. 595,094, filed July 11, 1975, (now
abandoned) which is in turn a continuation-in-part of LeVeen
application Ser. No. 436,102, filed Jan. 24, 1974 (now abandoned),
and is related to LeVeen application Ser. No. 595,095, filed July
11, 1975, now U.S. Pat. No. 4,032,860 which describes apparatus
suitable for carrying out radio frequency treatment of tumors in
accordance with the present invention.
Claims
I claim: .[.1. In the method of treating a naturally occurring
tumor in a human by placing the portion of the body of the human in
which the tumor is located in a radio frequency electromagnetic
field thereby to heat the tumor tissue in said portion of said body
by absorption of energy from said radio frequency electromagnetic
field for a period of tiime and with intensity sufficient to cause
necrosis of said tumor, but insufficient to cause significant
damage to the adjacent normal tissue in said field, the improvement
which comprises inducing hypotension in said human while treating
said tumor with said radio frequency electromagnetic field..].
The method according to claim 1 in which said hypotension is
induced by
use of drugs. 3. The method according to claim 1 in which said
hypotension is induced by the use of a drug selected from the group
consisting of vasodilators, vasodepressors, anti-hypertensive
agents and alpha-blocking
agents. 4. The method according to claim 1 in which said
hypotension is induced by the use of a drug selected from the group
consisting of trimethaphan camsylate, erythrityl tetranitrate, amyl
nitrate and
phentolamine. .Iadd.5. A method of treating a naturally occurring
tumor in a human comprising: placing a portion of the body of the
human in which the tumor is located in a radio frequency
electromagnetic field ranging in frequency from 100 kilohertz to
less than 1000 megahertz, heating the tumor tissue in said portion
of said body by absorption of energy from said radio frequency
electromagnetic field for a period of time and with intensity
sufficient to cause necrosis of said tumor, but insufficient to
cause significant damage to the adjacent normal tissue in said
field,
while inducing hypotension in said body portion..Iaddend. .Iadd.6.
A method of treating a naturally occurring tumor in a human
comprising: placing a portion of the body of the human in which the
tumor is located in a radio frequency electromagnetic field ranging
in frequency from 100 kilohertz to 200 megahertz, heating the tumor
tissue in said portion of said body by absorption of energy from
said radio frequency electromagnetic field for a period of time and
with intensity sufficient to cause necrosis of said tumor, but
insufficient to cause significant damage to the adjacent normal
tissue in said field, while inducing
hypotension in said body portion..Iaddend. .Iadd.7. A method of
treating a naturally occurring tumor in a human which comprises
placing a portion of the body of the human in which the tumor is
located in a radio frequency electromagnetic field ranging from 100
kilohertz to 200 megahertz, heating the tumor tissue and adjacent
normal tissue in said portion of said body by absorption of energy
from said radio frequency electromagnetic field for a period of
time and with intensity sufficient to heat said tumor tissue at
least 6.degree. C. above the temperature of the adjacent normal
tissue to cause necrosis of said tumor tissue, but insufficient to
heat said adjacent normal tissue above 40.degree. C. to cause
significant damage to the adjacent normal tissue, while inducing
hypotension in said body portion..Iaddend. .Iadd.8. The method
according to claim 7 wherein said tumor tissue is heated in a range
of 6.degree. C. to 10.degree. C. above the temperature of the
adjacent normal tissue..Iaddend. .Iadd.9. The method according to
claim 7 wherein said radio frequency electromagnetic field is 13.56
megahertz..Iaddend.
Description
This invention relates to the treatment of tumors in animal hosts,
such as human beings, and in particular provides a technique for
destroying the tumor without injury to adjacent normal tissues. The
tumors can be either benign or malignant and include carcinomas,
sarcomas, cysts and avascular lesions.
It is an important object of this invention to provide a method
applicable to the treatment of tumors under a wide variety of
conditions which can be utilized with a minimum, and preferably an
absence, of surgery.
It has been noted that tumors can be affected by hyperthermia
(Brit. of Cancer No. 25:771, 1971; Cancer Research No. 32:1916,
1972). This observation was coupled with the statement that the
tumors were heat sensitive. Experiments with external surface
heating do not produce deep heating and in some cases, using
hyperthermia, the whole animal was heated as much as the tumor.
Others have felt that a slight raise in temperatures produced by
metabolic changes in the cancer interfered with cell growth (Europ.
J. Cancer 9:103, 1973). Others have heated tumors for a few degrees
by diathermy to observe the effect on the tumor which was
inhibitory but not obstructive (Zelt. fur Naturforschung 8,25:359,
1971). There is still considerable disagreement and conflicting
evidence of the role heat may play in the treatment of cancer (The
Lancet, May 3, 1975; 1027).
Anatomical studies suggest that the blood flow through carcinomas
and other neoplasms is sluggish (Acta Pathalogica Microbiologica
Scand., 22:625, 1945; Advances in Biology of the Skin, 21:123,
1961). Tumors possess an angiogenetic factor which initiates the
formation of new blood vessels. These blood vessels, however, are
capillaries which because of their small diameter offer great
resistance to blood flow. The capillaries make connections with the
normal capillaries on the periphery of the tumor and are tortuous
following haphazard pathways before emptying into some small vein
at the periphery of the tumor. Frequently there is marked venous
obstruction within the tumor caused by compression of the
peripheral veins due to enlargement of the tumor and sometimes due
to ingrowth of tumor cells into the blood vessels obstructing
them.
Anatomical studies also demonstrate the presence of arterio-venous
fistulae at the periphery of tumors which can cause the tumors to
appear vascular on angiography because of the rapid appearnce of
contrast media, but which actually deprive the tumor of the blood
supply. The arterio-venous fistulae at the periphery of the tumor
tend to create a low resistance pathway at the surface of the tumor
which lowers the arterial pressure and diverts blood from entering
the tumor.
Although anatomical studies suggest that the tumor blood flow is
diminished and slow, only angiographic studies have functionally
confirmed that blood flow through tumors is actually sluggish
giving rise to an appearance of nonfilling on angiography. Residual
contrast medium remains in the tumor after it has been swept out of
the adjacent normal tissue by normal blood flow. This remaining
residual contrast medium has been called a "Tumor Stain". The
tumors which have been studied radiographically have been brain
tumors and kidney tumors.
This has been confirmed by the applicant by the indicator dilution
technique measuring the actual flow of blood through normal tissue
and through tumors. The indicator dilution techniques is more
reliable than the visual method as seen on angiography. Such
studies were done in vivo using X-ray contrast medium dilution and
in vitro on excised specimens. In the excised specimens blood flow
was measured by indicator dilution technique using radioiodinated
serum albumin. The albumin molecule was tagged with I.sub.131 and
the isotope dilution was measured in the tumor and in normal tissue
by a columnated scintillation counter. These studies indicated that
the magnitude of flow through the adjacent normal tissue is such
that the tumor tissue is differentially heated when the area of the
body containing the tumor is treated by diathermy.
In accordance with this invention, tumors are destroyed in humans
and other animals by heating the portion of the body containing the
tumor such that the temperature of the tumor is raised to a point
at which the tumor is necrosed, i.e., at or above about 50.degree.
C. In some instances necrosis of the tumor is achieved at
temperatures as low as 46.degree. C. Such temperatures, of course,
also destroy or severely damage normal tissue and the present
invention is based on the discovery that when a portion of the body
is heated, for example, by applied radio frequency electromagnetic
radiation, the tumor is heated differentially to a greater extent,
such that the temperature of the normal tissue adjacent the tumor
can be kept below 40.degree. C.
This is caused primarily by the normal blood flow in the adjacent
normal non-cancerous tissue. Thus, the temperature at which tissue
is heated depends upon the blood supply to the tissue. Although the
blood itself is heated, it serves to carry heat away from the part
being heated. As a result, tissue which are poorly perfused with
blood become heated more rapidly and to a higher temperature than
tissues which have a normal rate of blood flow. As pointed out
above, cancerous and other malignant and benign growths develop
outside a preformed blood vessel distribution network and derive
their blood supply from the periphery of the tumor where it meets
the adjacent normal blood supply. As a consequence, the slow rate
and volume of blood flow through the tumor provides a lesser
cooling rate in the tumor than the flow of blood through the normal
tissues adjacent the tumor.
Thus, when, for example, diathermy is applied in vivo to tissue
containing a tumor, the tumor is heated more than the adjacent
normal tissue. If the applied radiation is of sufficient intensity
and for a sufficient duration of time the differential heating of
the tumor can necrose the tumor without significant thermal injury
to the adjacent normal tissue.
In accordance with this invention diathermy can be used to produce
differential heating of cancerous tissue in the body. Insulated
applicators, which are connected to the output of an R.F.
generator, are placed on opposite sides of the portion of the body
adjacent the location of the tumor such that the applicators
produce localized heating in the tumor differentially higher than
the remaining normal tissue, adjacent to the tumor, which is in the
path of the R.F. radiation, i.e., generally between the
applicators. Heating the tissue between the applicators is
continued for a duration of time and at an intensity sufficient to
cause necrosis of the tumor by heating the tumor to about
50.degree. C. or above. In some cases tumor necrosis can be caused
by heating to temperatures as low as 46.degree. C. In any event
heating is insufficient to raise the temperature of the surrounding
normal tissue to cause significant damage to that tissue because
such adjacent tissue is cooled by its normal blood supply.
This effect of destroying tumors by differential heating has been
confirmed in both human cancers and cancers in animals by
simultaneous measurement of the temperature in the tumor and in the
adjacent normal tissue. Differential thermometry between the tumor
and normal tissue is performed with non-metallic thermometers
having non-electrolyte fluids, such as liquid alcohol filled
thermometers. Normal tissue is irreversibly damaged at temperatures
above 50.degree. C. (Chic. Med. Sch. Q 17:49, 1956). Temperatures
as high as 60.degree. C. can easily be achieved in the tumor while
the adjacent normal tissue is heated only to the vicinity of
40.degree. C. using about 100 watts of energy at 13.56 MHz.
Generally, the radio frequencies employed should be as low as
permissible in order to enhance the absorption of the energy by the
tissue. Consequently, the lower frequencies permitted by the F.C.C.
are preferable. Since most tumors are located within the body,
penetration of the heating radiation through the location of the
tumor is essential. It is well known that penetration of the body
by electromagnetic radiation and absorption of the energy of that
radiation is an inverse function of frequency. Generally, the
practical frequency range for use of diathermy as described above
to produce internal heating which can be utilized in the treatment
of tumors in accordance with this invention is from about 100
kiloHertz to about 200 megaHertz. As in this range the longer
wavelengths are both more effective in terms of heating and less
likely to cause damage by scattering and the like, as occurs in the
microwave region, the preference is distinctly for the longer
wavelengths. The preferred frequency for treatment is 13.56
megaHertz because it is the longest wavelength presently permitted
by law.
With impedance matching the results of this invention are generally
achieved with energies ranging between 50 and 250 watts and for
periods of times typically of 10 to 20 minutes, although lower and
higher power levels and longer and shorter periods of time can be
used depending on the size and location of the tumor. The
conventional diathermy machine can not provide the necessary heat
and has the disadvantage that the distribution of heat in the
tissues is apt to be non-uniform and can not always be predicted.
Also a considerable amount of energy on the standard diathermy
machine is often reflected back into the diathermy machine without
entering the tissue. Thus, it is difficult to determine the dosage.
Utilizing the energies required in accordance with this invention,
the conventional machine itself and the cables become very
overheated. These problems are readily overcome utilizing higher
power output R.F. generators and heavier cables so that energies on
the order required can be applied to the portion of the body under
treatment. Generally, the construction of suitable R.F. generators
and transmission cables are not unlike those utilized in industry
for relatively low power outputs, i.e., on the order of 1 kilowatt
in the frequency range under consideration. While such a power
level is high for diathermy use, it is not uncommon in many other
applications, including radiotelephony, induction heating, and the
like. The basic equipment is thus conventional.
It is preferred in present usage to employ an applicator generally
having the shape of a paddle, i.e., having a handle and a round
plate more or less coplanar with the end of the handle. The plate
itself is a conductive metal disc which is coated with an
insulating film of nonlossy material, such as a coating of
polyurethane resin, and is connected to the power source through
the handle of the applicator. Suitable applicators which have been
used have copper plates 2 inches to 4 inches in diameter. Also flat
copper spirals have been used with success. The leads to the
applicators from the power amplifier, of course, are necessarily
insulated and preferably are shielded cables, such as coaxial
cables, with the outer sheild grounded, as peak voltages on the
order of 300 volts are developed in the output circuit of the R.F.
amplifier. The applicators and cables should be waterproof and be
sterilized before use.
The applicators are connected across the radio frequency output in
the present usage of an amplifier capable of up to 2000 watt
output. The impedance of the load, i.e., the body portion between
the applicators, is of course variable, thus, the normal impedance
matching procedures utilized in coupling the output circuits of an
R.F. generator through a transmission line to a load can be
utilized. The transmission line, i.e., coaxial cables, are
connected appropriately at the output tank coil or otherwise in the
final stage of the R.F. generator to provide a proper impedance
match to the transmission line and impedance matching of the end of
the transmission line, i.e., the applicators, to the load is
important. In some circumstances, it has been found feasible to use
fixed impedance matching at the applicators by building series
inductance in the handles of the applicators, but this is not
necessary as separate adjustable provision for matching the load
can be utilized. Without proper impedance matching the power
requirements are much greater and damage to the R.F. amplifier can
occur.
Although it is not essential in carrying out the process of this
invention, desirably in a sophistocated unit, provision is thus
made for measuring both forward and reflected power. Similarly,
fail-safe precautions should be utilized to prevent a control
failure resulting in application of full load of the R.F. generator
to the applicators when only a partial load is desired.
Selective heating of tumors in accordance with the present
invention utilizing radio frequency electromagnetic energy can be
further accentuated by the use of drugs. Vasodilators increase
tissue blood flow, but reduce the blood flow to tumors and further
decrease the tumor oxygen tension (Acta Radiol 58:401-434, 1962;
Cancer 20:60-65, 1967). The use of vasodilators in connection with
radio frequency treatment in accordance with the present invention
should be of beneficial effect both because of the increased flow
produced through contiguous normal tissue will better dissipate
heat generated by the radio frequency energy while the slower flow
through the tumor will accentuate the elevation of the tumor
temperature.
It has also been noted that with hypotension, perfusion of blood
through a tumor ceases and the tumor blanches (J. Natl. Canc.
Instit. 12:399-410, 1951). Consequently, the use of hypotensive
agents can improve the effects of radio frequency treatment in
accordance with the present invention. Similarly, radiation, tumor
embolism, alteration of blood viscosity and compression can all be
used to advantage.
When the tumor tissue has been necrosed it becomes a fluid. This
fluid may be removed naturally by the body but aspiration has also
been found desirable at times. Care should be taken to prevent
sepsis and the use of antibiotics may be indicated.
Treatment in accordance with the present invention should be with
care to avoid overheating normal tissues such as cartilage which
have no blood supply. The presence of bile in the gall bladder may
also cause a problem when treatment requires application to a
portion of the body including the gall bladder.
For a more complete understanding of the practical application of
this invention, reference is made to the appended drawings in
which:
FIG. 1 is a block diagram indicating an apparatus set-up for
carrying out the process of this invention;
FIG. 2 is a plan view of an applicator suitable for carrying out
the process of this invention.
FIG. 3 is an enlarged, fragmentary section taken at line 3--3 in
FIG. 2;
FIG. 4 is an end view of a portion of another applicator suitable
for carrying out the process of this invention;
FIG. 5 is an elevational view of the applicator shown in FIG. 4
indicating its use in relation to the portion of the body being
treated; and
FIG. 6 is an electrical schematic diagram of the applicator shown
in FIGS. 4 and 5.
Referring to FIG. 1, a simple arrangement of apparatus for carrying
out the process of this invention involves an exciter 10, a power
amplifier 20, and a pair of applicators 30. Both the exciter 10 and
power amplifier 20 are conventional. Exciter 10 has a crystal
controlled oscillator, in the illustrated case operating on 13.56
mHz. Exciter 10 has an output of between 2 watts and 110 watts
dependent on the bias of the oscillator; the less negative the bias
the higher the output of exciter 10. An oscillator variable bias
supply 40 functions to control the bias and the oscillator and
hence the output of exciter 10.
Power amplifier 20 is designed to amplify the output of exciter 10,
and to this end the output circuit of exciter 10 is connected to
the input circuit of power amplifier 20 as denoted by the reference
numeral 11. Power amplifier 20 is designed for an output of 30
watts to 1,000 watts dependent upon the output of exciter 10, and,
of course, is turned to the same frequency of 13.56 mHz.
The output circuit of power amplifier 20 is connected to energize
applicators 30 by means of coaxial cables 21. Cables 21 have their
inner conductors 22 connected across the tank circuit of the output
of power amplifier 20 and lead to applicators 30, as more fully
described with respect to FIGS. 2 and 3. As shown in FIG. 2, each
coaxial cable 21 includes a central conductor 22 which is provided
with insulation 23 over which there is a braided shield 24 and an
outer jacket 25. The two conductors 22 are connected across the
tank coil in the output circuit of power amplifier 20, or
optionally one can be grounded. In either case, the two shields 24
are grounded at the power amplifier, and, as shown in FIG. 1, are
preferably also provided with an interconnection 26 between shields
24 adjacent the handle 31 of each applicator 30.
Generally applicators 30, as can be seen best in FIG. 2, are in the
shape of a paddle having a handle 31 and an applicator portion
32.
Each handle 31 is made of insulating material, such as a phenolic
resin, and, as can be seen best in FIG. 3, is hollow such that
coaxial cable 21 is brought into the end of handle 31. The
applicator portion 32 is secured to handle 31 at the end of handle
31 opposite that into which cable 21 leads and is in the form of a
flat, circular copper disc 34 which is electrically connected at
its periphery adjacent the end of handle 31 to the end of conductor
22.
As illustrated in FIG. 3, copper plate 34 is provided with an
insulating coating 35 such that electrical contact with plate 34
can only be made through conductor 22. Coating 35 should be of
non-lossy insulating material in order to minimize the generation
of heat in the insulation itself. Suitable insulation materials are
characterized by low dissipation factors generally below about
0.01, and can be, for example, Mycalex (a proprietary glass and
mica insulating material), polyethylene, polytetrafluorethylene,
polystyrene, and polyurethanes. Polyurethanes are particularly
desirable since they are readily applied as liquids which set to
form smooth, even and thin coatings.
Applicators 30 should have diameters such that when the portion of
the body containing the tumor is placed between them they will be
sufficiently large to place the entire tumor within the densest
portion of the electromagnetic field set up when they are
energized. It will be apparent that, as described above,
applicators 30 function electrically as a capacitor such that the
portion of the body between the electrodes is effectively between
the plates of a capacitor. Heating occurs even though the body
tissue is basically an electrolyte rather than a dielectric
material. The electric and magnetic fields which are set up,
however, are those which would be set up between condenser
plates.
It has also been found that heating in accordance with this
invention can be obtained where the applicator structure is
basically an inductance. Thus, referring to FIGS. 4, 5, and 6,
there is shown an apparatus for developing and directing a radio
frequency electromagnetic field in one direction with the energy
confined to a desired region for localized heating of, for example,
body tissue. The basic apparatus involves three essentially
identical circuit units 50, 60, and 70.
Each unit 50, 60, and 70 includes a pancake coil 51, 61, and 71,
respectively, which is in the form of a planar spiral of flat
silver-plated copper having three turns from the inner to the outer
end. Variable (0-250 pf) vacuum capacitors 52, 62, and 72 are
respectively connected across each spiral coil 51, 61, and 71. Each
spiral coil 51, 61, and 71 is housed in a circular
polytetrafluoroethylene (PTFE) disc 53, 63, and 73, respectively,
which is grooved appropriately to receive its associated spiral
coil 51, 61, and 71 with the connections of such spiral coil
extending from the PFTE disc for connection to its associated
vacuum capacitor 52, 62, or 72. The open side of each PTFE disc,
i.e., the side in which grooves are machined to receive the
associated spiral, is covered with a thin plate of Mycalex 54, 64
and 74 to retain the associated spiral coil 51, 61, and 71,
respectively, within its associated PTFE housing.
Unit 50 has its spiral coil 51 and capacitor 52 connected in
parallel across the output of an R.F. power amplifier, such as
amplifier 20, and is considered as the driver section which sets up
an electromagnetic field when energized by power amplifier 20.
Unit 60 is mounted on a common housing of dielectric material with
unit 50 such that they are parallel to each other and axially
aligned spaced apart 6 inches when using a frequency of 13.56 mHz
to energize unit 50. As a result, the electromagnetic field
developed by unit 50 when energized is actually directed with
regard to its magnetic component axially toward and through unit 60
(to the right as shown in FIG. 5). For convenience sake, unit 60
may be regarded as a focus section.
Unit 70 is positioned parallel to unit 60 and axially aligned with
it on the side of unit 60 opposite unit 50 and functions as a
reflector section confining the electromagnetic field such that an
object placed between units 60 and 70 can be heated by the
electromagnetic radiation between units 60 and 70. These units are
then utilized in accordance with this invention in the same manner
as applicators 30. At a frequency of 13.56 mHz, spiral coils 51,
61, and 71, each, can have three turns with an overall diameter on
the largest turn of 5.5 inches and with the turns spaced about
three eighths inch on center. The distance between units 60 and 70
can be from 5 to 15 inches to accommodate the portion P of the body
to be treated.
In utilizing the arrangement of FIGS. 4, 5, and 6, the driver unit
is adjusted by adjusting capacitor 52 into resonance with spiral
51. The impedance of the unit as described above should be about 50
ohms at this point. Units 60 and 70 are also adjusted by means of
their associated condensers 62 and 72 to resonance and maximum
loading.
The above adjustments can all be made at a relatively low power
output. The body portion P to be treated is then positioned between
units 60 and 70 and the desired power output of amplifier 20 is
then turned on to treat body portion P. In the following
discussion, where the word "applicators" is used, reference is
intended to applicators, such as applicators 30, and equally to
applicators, such as units 60 and 70, unless the context clearly
indicates otherwise.
Preferably, the applicators are placed firmly and in intimate
contact with the surface of the body portion under treatment in
order to minimize "hot spotting" which can occur when the surface
of the body is of irregular contour. Indeed, such "hot spotting" is
further minimized by using electrode paste on the surface of the
portion of the body under treatment, and bronze wool or woven
stainless steel in the form of a sleeve can be placed over the
applicator further to minimize the effects of skin resistance. Such
a sleeve typically is on the order of one-half to one inch thick,
is compressible, and hence, takes up any irregularity on the
surface contour of the body. Intimate contact, however, is not
essential and in using fixed-tuned applicators it has been found
that on occasion more effective results have been obtained by
backing one of the applicators away from the surface of the body
where the portion under treatment was relatively narrow and not
optimum for the particular applicator.
Tissue temperatures during therapy can be determined by inserting
into the tissue being heated non-metallic thermometers having
non-electrolyte indicator fluids, such as glass alcohol
thermometers. It is essential that during therapy the adjacent
normal tissue temperature be raised only to 40.degree. C., as
higher temperatures can cause its destruction as well. With
increased skill, a surgeon can avoid the necessity of using
thermometers, as he can sense the temperature of the normal tissue
by palpation when the diathermy is turned off. In order to destroy
the tumor it is usually essential that its temperature be raised
above 50.degree. C. In some instances the tumor tissue can be
necrosed at temperatures as low as 46.degree. C. Destruction of the
tumor can be observed either by thermometric means, by X-ray
techniques used to sense the presence of the tumor, biopsy and the
like.
In some instances, for example, cancer in some human organs, such
as the liver, is treated by surgically exposing the organ to place
the applicators directly in contact with the organ at the location
of the cancer.
In the case of human lung carcinoma, both metastatic and primary,
the applicators can be applied to the external chest wall. Massive
necrosis of the lung tumor can induce complications of pulmonary
abscess or hemorrhage, but these can be dealt with surgically after
all the tumor has been destroyed.
Similarly, it may be necessary to divert the fecal stream with a
proximal defunctionalizing colostomy, when rectal and colon tumors
are treated to avoid the danger of necrosis with perforation.
Other avascular lesions occurring in otherwise normal tissue will
respond equally to this therapy. Similarly, polycystic kidneys can
be treated, since the cysts have no blood supply they will be
heated while the vascular kidney substance will remain cool. Thus,
the therapy will destroy the lining of the cyst wall which secretes
fluid and causes compression atrophy of the normal kidney.
EXAMPLE I
A 67 year old white male had an undesectable carcinoma of the left
lung which proved on biopsy to be a squamous cell. He had mild
dyspenea and dull pain on the left side of his chest and a brachial
neuralgia.
The apparatus generally described with reference to FIG. 1 was
utilized, and applicators 30 were in the form of a pair of copper
plates 34 of 4 inch diameter and one-eighth inch thickness. The
applicators were fixed-tuned by incorporating in series between the
connection of conductor 22 and plate 34 a coil located within
handle 31 which consisted of six turns of 20 AWG copper wire with a
one-half inch outside diameter (wound about a pencil) and one-half
inch in length. The coil and its connections to conductor 22 and
plate 34 were potted using silicon rubber composition within handle
31. Coaxial cable 21 was of the type known as RG 58-U and was three
feet in length in each case. Insulated coating 35 was 4 mils thick
and was a clear polyurethane resin containing no oxides.
The applicators 30 were positioned one flat against the anterior
and the other flat against the posterior of his chest to position
the tumor between them. The patient was given general anesthesia
and the applicators 30 were energized at an indicated power level
of 200 watts for 20 minutes at 13.56 mHz. The voltage (R.M.S.)
across applicators 30 at this level was 100 volts. No measures were
taken to insure intimate contact with the skin and applicators 30.
Consequently, a skin burn resulted.
Three days later a thoracotomy was done to biopsy the lesion. The
entire tumor was incised and a large biospy taken. This biospy was
reported as inflammatory reaction only, although the surgeon was
sure he had incised the tumor. Subsequently, the patient's course
has shown gradual improvement. His brachial neuralgia has cleared
and his chest X-rays are improved. The treatment resulted in
considerable necrosis of the chest wall. This has now healed
completely.
EXAMPLE II
In this Example the patient was a 57 year old white male who had
undergone total laryngectomy for carcinoma of the vocal cords
approximately two years before treatment. Approximately 4 months
before treatment, the patient developed a large mass the size of an
orange (3 inches in diameter) over the manubrium of the sternum
(breastplate bone). Biopsy showed it to be a squamous cell
carcinoma.
The tumor was irradiated (Cobalt) but there was no substantial
improvement and no reduction in the size of the mass. He was deemed
inoperable by thoracic surgery. The tumor mass was stoney hard; the
skin overlying the mass was stretched and shiny; and the tumor has
pushed the tracheotomy to the right. There was also invasion of the
underlying bone. The patient was having respiratory difficulty
because the tumor compressed the trachea and his situation was
desperate.
This patient was given four treatments utilizing generally the
apparatus shown in FIG. 1 with the four inch applicators 30
described above in Example I. Prior to positioning the applicators,
the skin of the patient was moistened with EKG jelly to decrease
skin resistance, and a bronze wool sponge was placed over the
location of the tumor on each side to maintain even electrical
contact. One applicator 30 was then placed flat against the bronze
sponge over the tumor with the second applicator 30 placed flat
against the midaxilla. Thus, in effect, the patient's body was
positioned between the two applicators 30 such that the tumor was
located between them.
Indicated power was initially raised gradually to 300 watts (about
120 volts R.M.S. at 14.56 mHz) and maintained for 20 minutes
between 275 and 300 watts.
One week later, the hard mass has become softer and fluctant in
parts. Ten days after the treatment the mass was aspirated and
semi-liquid, necrotic material was withdrawn. In order to further
liquify the necrotic material Bovine fibrinolysin and
desoxyribonuclease were injected into the tumor. Two days later,
the tumor was again aspirated.
Nineteen days after the first treatment, the patient was given a
second treatment with the four inch applicators 30 again placed in
the same manner except that the second applicator was placed on the
back of the chest to the right of the midline. Treatment was for 20
minutes. Again the indicated power was gradually increased this
time to 385 watts (135 volts R.M.S. at 13.56 mHz) and then varied
between 350 and 410 watts during the remainder of the therapy.
Two weeks later, the tumor was aspirated again. Liquid material was
obtained and the tumor had decreased considerably in size. No
viable tumor cells were shown. There were some autolyzed cells. The
third treatment immediately followed such aspiration and was
similar to the first treatment except that initial power was 135
watts which was increased to 235 watts (108 volts R.M.S. at 13.56
mHz) and continued for a total of 11 minutes.
Although further therapy was considered superfluous, since the
tumor had already been destroyed, a fourth treatment was given ten
days later. In this instance, applicators 30 were placed one on the
midaxilla, as described above, and the other first to the right and
then to the left of the tumor. In each case, the skin was moistened
with EKG jelly and bronze wool sponge is placed against the skin
beneath the applicator 30 to maintain even electrical contact. The
treatment was at 475 watts (150 volts R.M.S. to 400 watts (138
volts R.M.S. at 13.56 mHz) on the right side for 20 minutes.
The final pathological diagnosis indicated no malignancy. The mass
has almost completely disappeared although there is some
inflammation and an ulcer under the site of the necrotic tumor.
Before treatment in accordance with this invention the patient was
having severe respiratory difficulty because the tumor was closing
off his trachea just below the site of the tracheotomy. Since the
treatment, the patient can breathe freely and has had no
respiratory difficulty. Therapy in accordance with this invention
resulted in minimal necrosis of the stretched skin over the lesion
which will require future grafting.
EXAMPLE III
In this case the patient had what was considered to be a large,
inoperable carcinoma of the lung which filled the entire right
upper chest. The tumor mass was larger than the 4 inch applicators
30 which were available. One applicator 30 was put on the anterior
portion of the chest wall after moistening the skin with conductive
paste, and the other applicator 30 was similarly positioned on the
posterior of the chest wall, such that the tumor mass was largely
positioned between them. Fluoroscopy was utilized to define the
location of the tumor mass. The patient was not anesthesized.
The apparatus was turned on to apply an indicated 50 watts and then
increased to 256 watts (112 volts R.M.S. at 13.56 mHz) over a three
minute interval. Power was then gradually decreased to 175 watts
(90 volts) for the remainder of the period of 20 minutes.
Four days later a second treatment was given to the patient with
the same positioning of applicators 30 in which power was gradually
increased over a 9 minute period to 215 watts (105 volts) and then
slowly lowered to 185 watts for 1 minute. The power level was then
increased to 375 watts and kept for a four minute interval and
thereafter between 300 and 350 watts for the rest of the 20
minutes. Because of the size of the applicators, the treatment was
considered spacially inadequate to reach the entire tumor.
Five days later a right upper lobectomy was done. The entire right
upper lobe was necrotic with severe inflammatory reaction. The
entire lobe was fixed and cut on a large microtone. Ninety-nine
percent of the tumor was necrosed but a small rim of tumor was
still present where the applicators had not completely covered the
tumor. All of the treated area was entirely free of tumor, as the
tumor in the treated area was dead and undergoing autolysis.
In this case the inoperable carcinoma was considered to have been
made operable since the tumor tissue adherent to the pleura and
chest wall was completely necrotic and the lesion could be removed
without leaving live tumor.
In each of the preceding Examples, the apparatus did not have
provision for adjustable impedance matching or for measurement of
forward and reflected power. The power levels indicated were based
on input to the final stage of the amplifier and were probably two
or three times that actually applied to the body being treated.
MEASUREMENTS OF TUMOR TEMPERATURE
Temperature recordings were made in human tumor tissue before and
during R.F. therapy in six patients. Oral temperature was also
recorded. In three patients, the temperature of the tissue adjacent
to the located tumor tissue was also recorded. Temperature
measurements were performed in those patients whose tumors were
accessible to a needle type temperature probe. The t.degree.
recorded in the tumor before and during R.F. treatment and body
temperature is shown in Table I. The mean tumor temperature
following R.F. treatment was significantly higher than that before
treatment (p<0.001) and that of body temperature
(p<0.001).
TABLE I ______________________________________ Temperature
Elevation With R.F. (C..degree.) A. Max. Body B. Tumor C. T.degree.
during D. Normal T.degree. during Prior R.F. Adjacent Patient R.F.
R.F. Treatment Tissue T.degree.
______________________________________ 1 37.5 39.1 48.0 -- 2 38.5
37.2 48.5 40.0 3 38.0 38.0 49.5 -- 4 38.2 38.0 48.5 39.7 5 36.0
37.2 46.0 -- 6 37.0 37.6 49.5 -- 7 37.1 37.2 49.5 39.0 Mean 37.5
37.9 48.4 39.5 ______________________________________ Statistical
analysis Standard p test for paired data. C vs. A, i = 23.58 p
<0.001; C vs. B, i = 19.80 p <0.001.
ADMINISTRATION OF HYPOTENSIVE AGENTS
As indicated above, inducing hypotension during treatment is useful
in accentuating the differential heating of tumor tissue exposed to
radio frequency electromagnetic radiation in accordance with this
invention. The use of vasodilators, vasodepressors,
anti-hypertensive agents and alpha blocking agents reduces the
blood flow through the tumor. Typical agents which can be used are
trimethaphan camsylate, erythrityl tetranitrate, amyl nitrate, and
phentolamine. In inducing the hypotension during radio frequency
treatment in accordance with the present invention, the following
procedure is suggested:
Hypotension is maintained at a level of about 60-70 mm. of mercury
for the duration of a one-half radio frequency treatment. The
tolerance of patients varies from individual to individual and some
individuals can easily tolerate hypotension of 50 mm. of mercury
for 30 minutes. Care is exercised to keep the head low especially
if the part to be treated is elsewhere than the head. When
trimethaphan camsylate (Arfonad) is the hypotensive agent, one
ampule of 10 ml. of Arfonad containing 50 mg. per ml. is diluted to
500 cc. in 5% glucose in distilled water. An intravenous drip is
started and the initial rate of administration given is 60 drops
per minute. The blood pressure is taken every five minutes during
the administration of the hypotensive agent. There is a marked
variation in the patient's response and the rate of infusion must
be frequently adjusted to maintain the blood pressure at the
desired level. If there is any evidence of fainting or cerebral
anoxia, the infusion is slowed and the blood pressure is allowed to
come up to a higher level. In thin patients, the rate of drug
administration can be as slow as four drops per minute, while in
other patients, 100 drops per minute is sometimes required.
Therefore, the blood pressure is used as an indication of proper
dosage rather than the total amount of drug which the patient
receives. The blood pressure promptly returns to normal upon
cessation of the drug although the return toward normal can be
hastened by the administration of vasopressor drugs.
* * * * *