Note: Descriptions are shown in the official language in which they were submitted.
`- I ~ 107Z186
1 ¦ S P E C I F I C ~ T I O N
2 I
S I
¦ This invention relates to the treatment of tumors
5 ¦in animal hosts, such as human beings, and in particular
6 ¦provides a technique for destroying the tumor without injury
7 ¦to adjacent normal tissue. The tumors can be either benign
¦or malignant and include carcinomas, sarcomas, cysts and
9 ¦avascular lesions.
10 ¦ It has been noted that tumors can be affected by
11 ¦hyperthermia ~Brit. of Cancer 25:771, 1971; Cancer Research
12¦ 32:1916, 1972). This observation was coupled with the
13 ¦statement that the tumors were heat sensitive. Experiments
14 ¦with external surface heating do not produce deep heating
15 land in some cases, using hyperthermia, the whole animal was
16 Iheated as much as the tumor. Others have felt that a slight
17 ¦raise in temperatures produced by metabolic changes in the
18 ¦cancer interfered with cell growth (Europ. J`. Cancer
'9 ¦9:103, 1973). Others have heated tumors for a few degrees
20 ¦by diathermy to observe the effect on the tumor which was
21 ¦inhibitory but not obstructive (Zelt. fur Naturforschung
22 8,~-26:359, 1971). ;
23 Anatomical studies suggest that the blood flow
24 through carcinomas and other neoplasms is sluggish (Acta
athalogica Microbiologica Scand, 22:625, 1945; Advances in
26 Biology of the Skin 21:123, 1961). Tumors possess an
27 angiogenetic factor which initiates the formation of new blood
28 vessels. These bood vessels, however, are capillaries which
29 ecause of their sm~ll diameter offer great resistance to
~lood flow. e c~pi1laries make Conne~tioD6 ~i h tDe normal
,' , . .. .
: ..... . , ' . ` ` ` ` ` ' ` ` ` . :, ~ . . `" ' :
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1¦ capillaries on the periphery of the tumor and are tortuous
¦~ollowing haphazard pathways before emptying into some small
3 Ivein at the periphery of the tumor. Frequently there is
4 ¦marked venous obstruction within the tumor caused by com-
¦pression of the peripheral veins due to enlargement of the
6 ¦tumor and sometimes due to ingrowth of tumor cells into the
Iblood vessels obstructing them.
8 ¦ Anatomical studies also demonstrate the presence
9 ¦of arterio-venous fistulae at the periphery of tumors which
10 ¦can cause the tumors to appear vascular on angiography
11 ¦because of the rapid appearance of contrast media, but which
12 actually deprive the tumor of-the blood supply. The arterio-
3 ¦venous fistulae at the periphery of the tumor tend to create
14 la low resistance pathway at the surface of the tumor which
¦lowers the arterial pressure and diverts blood from entering
16 ¦the tumor.
17 ¦ Aithough anatomical studies suggest that the tumor18 ¦blood flow is diminished and slow, only angiographic studies
19 ¦have functi~nally confirmed that blood flow, through tumors
20 ¦is actually sluggish giving rise to an appe,arance of non-
21 ¦filling on angiography. Residual constrast medium remains
22 ¦in the tumor after it has been swept out of- the~adjacent=~ -
23 ¦normal tissùe by normal blood flow. This remaining residual
24 contrast medium has been called a "Tumor Stain". The tumors
25 which have ~een studied radiographically have been brain
26 tumors and kidney tumors.
27 This has been confirmed by the applicant by the
28 indicator dilution technique measuring the actual flow of
29 blood through normal tissue and through tumors. The
30 indicator dilution technique is more reliable,than the visual
,
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l ¦method as seen on angiography. Such studies were done
2 ¦in vivo usinq X-ray contrast medium dilution and in vitro
¦on excised specimens. In the excised specimens blood flow
was measured by indicator dilution technique using radio-
5 iodinated serum albumin. The albumin molecule was tagged
6 with I and the isotope dilution was measured in the tumor
7 and in normal tissue by a columnated scintillation counter.
These studies indicated that the magnitude of flow through -
9 the adjacent normal tissue is-such that the tumor tissue is
10 differentially heated when the area of the body containing
~1 th~ tumor is trea~e~ ~y ~iatherny~
12 Thus, in accordance with this invention, tumors are¦
dest~ye~ hum~ns ~nd otl~er animal~ ~y ~.eati~g ~if~eren-
~4 tially, such that the temperature of the tumor is raised to
~5 a point at ~hich the tumor is necrosed, i.e., at or above -
16 about 50C. In some instances necrosis of the tumor is
~7 achieved at temperatures as low as 46C. Such temperatures,
18 of course, also destroy or severely damage normal tissue and
19 the present invention is based on the discovery that when a
20 portion of the body is heated by applied radio frequency,
21 electromagnetic radiation the tumor is heated differentially
22 to`~a greater extent, such that the temperature-of the normal--- .
23 tissue adjacent the tumor can be kept below 40C.
24 This is caused primarily by the normal blood flow
25 in the adjacent normal non-cancerous tissue. Thus the
26 temperature at which tissue is heated by induction or direct
27 passage of alternating current depends upon the blood supply
28 to the tissue. Although the blood itself is heated, it
29 serves to carry heat away from the part being heated. As a
30 result, tissues which are poorly perfused with blood become
.,
- _4_ -
' ' : '
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1 heated more rapidly and to a higher temperature than tissues
8 which have a normal rate of blood flow. As polnted out
3 above, cancerous and other mal ignant and benign growths
develop outside a preformed blood vessel distribution network
and derive their blood supply from the periphery of the tumor
6 where it meets the adjacent normal blood supply. As a con-
7 sequence, 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 tissue adjacent the tumor.
lQ Thus, when diathermy is applied to tissue contain-
11 ing a tumor, the tumor is heated more than the adjacent
i2 normal tissue. If the applied radiation is of sufficient
15 intensity and for a sufficient duration of time the differ-
14 ential heating of the tumor can necrose the tumor without
15 significant thermal injury to the adjacent normal tissue.
16 In accordance with this invention diathermy is used
17 to produce differential heating in the body by using
18 insulated conductive metal plates, i.e., applicators, which
9 are connected to the output of an R.F. generator ana wnlch
20 are placed in intimate contact with the body adjacent the
21 llocation of the tumor such that the applicators are located
221 on opposite sides of the tumor to produce localized heating
23 in the tumor differentially higher than the remaining normal
24 ¦tissue, adjacent to the tumor, which is in the path of the
26 IR.F. radiation, i.e., generally between the applicators.
26jiHeatillg the tissue between the applicators is continued for a
27 duration of time and at an intensity sufficient to cause
28 necrosis of the tumor by heating the tumor to about 50C or
29 above. In some cases tumor necrosis can be caused be heating
30 to temperatures as low as 46C. In any event heating is
1072186
1 ¦insufficient to raise the temperature of the surrounding
2 ¦normal e4~o to cause slgni~lcant damage to that tissue.
5 ¦ This effect of,destroying tumors by differential
¦heating has been confirmed in both human cancers and cancers
5 ¦in animals by simultaneous measurement of the temperature in
I the tumor and ip the adjacent normal tissue. Differential
7 ¦thermometry between the tumor and normal tissue is performed
8 ¦ with non-metallic thermometers having non-electrolyte fluids,
9l such as liquid alcohol filled thermometers. Normal tissue
~0~ is irreversibly damaged at temperatures above 50C. (Chic.
11¦ Med. Sch. Q 17:49, 1956). Temperatures as high as 60C can
; 121 easily be achieved in the tumor while the adjacent normal
~31 tissue is heated only to the vicinlty of 40C using about
14¦ 500 watts of energy at 13.56 MHz.
15¦ Genera~ly, the radio frequencies employed should be
16¦ as low as permissable in order to enhance the absorption of
171 the energy by the tissue. Consequently, the lower frequen-
18 ¦ cies permitted by the F.C.C. are preferable. The results of
19¦ this invention generally are achieved with energies ranging
20¦ between 200 and 500 watts and for periods of times typically
21¦ of 10 to 20 minutes, although lower and higher power levels -
. l ~, .
22 ¦and longer and shorter periods of time can be used depending
23 ¦on the size and location of the tumor. The conventional
24 ¦diathermy machine cannot provide the necessary heat and has
25 ¦the disadvantage that the distribution of heat in the tissues
26 ¦is apt to be non-uniform and cannot àlways be predicted.
27 ¦A1SO a considerable amount of the energy on the standard
28 ¦diathermy machine is often reflected back into the diathermy
¦machine without entering the tissue. Thus it is difficult to
30 ¦determine the dosage. Utilizing the energies required in
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l ¦a~cordance with this invention, the conventional machine
a 1itself ~d ~1~e cabies become very overheated.
3 ¦ In accordance with this invention it has been found
4 ¦that a device known as the Marzoli applicator can be utilized
5 ¦to supply the necessary energy input and distribution.
6 1 The ~larzoli applicator basically is in the form of
7 la pair of spiral discs, i.e., applicators, which are placed
8 ¦spaced apart confronting each other with the object to which
¦the radio requency energy is to be applied betwen them. The
¦spirals of the electrodes are the reverse of each other in
ll ¦this position, such that when they are adjacent each other
12 Ithe inductive effects of current flowing through them cancels.
13 ¦As they are moved apart the inductance (L) increases, but the
14 ¦capacitance (C) between them decreases correspondingly.
It is preferred, however, in present usage to
16 employ applicator generally having the shape of a paddle,
17 i.e., having a handle and a round plate more or less coplanar
18 with the end of the handle. The plate itself is a conductive
l9 metal disc which is coated with an insulating film, such as a
20 coating of polyurethane resin, and is connected to the power
21 source through a small coil contained in the handle of the
22 applicator. Suitable applicators which have been used have
23 copper plates 2 inches and 4 inches in diameter. The leads
24 to the applicators from the power amplifier, of course, are
25 necessarily insulated and preferably are shielded cables,
26 such as coaxial cables, with the outer shield grounded, as
27 peak voltages on the order of 300 volts are developed in the
28 utput circuit of the R.F. amplifier.
29 The app~icators are connected across the radio
30 fre~uency output in the present usage of an amplifier capable
````` 1072186
of up to 1000 watt output. `
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 one appratus
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
- 10 at line 3-3 in FIG. 2;
FIG. 4 is a schematic diagram of a control circuit
useful in stabilizing the power level of the apparatus shown
; in FIG. l; and
FIG. 5 is a block diagram of a safety circuit in
order to insure fail-safe operation of the apparatus shown
in FIG. 1 in the event of a breakdown in the control circuit
or the like.
Referring to FIG. 1 a simple arrangement of appa-
ratus for carrying out the process of this invention involves
an exciter 10, a power amplifier 20, and a pair of applica-
tors 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.
Power amplifier 20 is designed to amplify the
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. I ~ .
1 ¦ output of exciter 10, and to this end the output circuit o
~ ¦ exciter 10 is con~ected to the input circuit of power
5 ¦ amplifier 20 as denoted by the reference numeral 11. Power
¦ amplifier 20 is designed for an output 30 watts to 1,0~0
5 ¦watts dependent upon the output of exciter 10 and of course,
6 ¦is tuned to the same frequency of 13.56 MHz.
¦ The output circuit of power amplifier 20 is
8 ¦connected to energize applicators 30 by means of coaxial
¦cables 21. Cables 21 have their inner conductors connected
.0 ¦across the tank circuit of the output of power amplifier 20
1 ¦and lead to applicators 30, as more fully described with
i2 ¦respect to FIG.'s 2 and 3. As shown in FIG. 2, each coaxial
13 ¦cable 21 includes a central conductor 22 which is provided
14 ¦with insulation 23 over which there is a braided shield 24
~5 ¦and an ou-'er jac~et 25. The two conductors 22 are connected
16 ¦across the tank coil in the output circuit of power amplifier
17 ¦20, or optionally one can be grounded. In either case the
¦two shields 24 are grounded at the power amplifier, and, as
19 ¦shown in FIG. 1, are preferably also provided with an inter-
20 ¦connection 26 between shields 24 adjacent the handle 31 of
21 ¦each..applicator.30.
22 ¦ Generally applicators 30, as c~n be seen best in
23 ¦FIG. 2, are in the shape of a paddle having a handle 31 and
24 an applicator portion 32.
Each handle 31 is made of insulating material, such
26 as a phenol~c resin, and, as can be seen best in FIG. 3, is
27 hollow such that, as coaxial cable 21 is brought into the
28 end of handle 31, the central conduc`tor 22 is electrically
2 connected to a coil 33 positioned in handle 31. The applica-
tor portion 32 is secured to handle 31 at the end of handle
g ` ~
107Z186 1 .
1 ¦ 31 opposite that to which conductor 22 is connected and is2 ¦ ln the ~ n of a flat, clrcular copper disc 34 which is
3 ¦ electrically connected at its periphery adjacent the end of
4 ¦ handle 31 to the end of coil 33 remote from connection with
5 ¦ conductor 22.
¦ As illustrated in FIG. 3 copper plate 34 is pro-
7 ¦ vided with an insulating coating 35, for example of a poly-
-8 ¦ urethane resin, such that electrical contact with plate 34
9 ¦ can only be made through coil 33.
10 l Two sizes of applicators 30 have presently been
~1¦ constructed. In one copper plate 34 is 4 inches in diameter,
12 ¦and in the other copper plate 34 is 2 inches in diameter. In
13 ¦each case copper plate 34 is about 1/8 inch thickness. In
- ~4 ¦ the instance of the 4 inch plate coil 33 is 6 turns with an
15 ¦ outside diameter-of 1/2 inch (wound about a pencil) and is
16 ¦ 1/2 inch in length. Coil 33 is positioned in the center of
17 ¦ insulated handle 31 and potted using a silicone rubber
18 ¦ conlposition. In the case of the two inch copper plate 34
19 ¦coil 33 is again wound about a pencil and is 18 turns having
20 ¦ an outside diameter of 1/2 inch and is 1 inch in length.
21 ¦ Again coil 33 is potted in the handle using silicone rubber
22 composition. In each case, coil 33 is a copper wire about
23 ~ AWG. In each case coaxial cable 21 is of a type
24 known RG 58-U and is approximately 3 feet in length from
25 power amplifier 20 to the associated applicator 30. In each
26 case the thickness of insulated coating 35 is approximately
27 4 mils and is a polyurethane resin which is clear, containing
28 no oxides.
29 FIG. 4 illustrates a servo control generally desig-
30 nated by the reference numeral 40 in FIG. 1 in which the
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1 ¦ power output of power amplifier 20 is sensed and the ampli-
¦ flca~on ln exciter 10 is controlled to hold the power output
5 ¦ of amplifier 20 at any desired constant level which can be
4 ¦ pre-selected by manual control.
S ¦ In the arrangement shown in FIG. 4 the reference
6 ¦ numeral 27 indicates the tank circuit in the output stage of
7 ¦power amplifier 20 which includes a tank coil 41 and tuning
8 I capacitor 42 which are adjusted to resonance at 13.56 MHz
9 ¦ and are connected through a coupling condenser 43 to the
lO ¦plates of a pair of parallel output tubes indicated schemat-
11 ¦ically as a single tube 44. In the illustra*ed case these
;2 ¦are a pair of 3-500 Z triodes, connected as grounded-grid
13 ¦amplifiers, having a plate supply of approximately 2400 volts
14 ~DC.
15 ¦ Coupling capacitor 43 is .001 uf and tuning capa-
16¦ citor 42 is a variable capacitor having 10-250 pf. Tank
171 coil 41 has 5 turns and is grounded 1-1/2 turns above its
18¦ end remote from triodes 44 and is tapped at such end and
191 1-1/2 turns above the ground tap for connection to conductors
20¦ 22 through a double pole switch 45 in one mode of connection
21¦ of such switch. The other mode of connection of such switch-
22¦ is utilized when only one applicator 30 is to be used and
23¦ the other side is grounded.
241 Also approximately 2 turns from the high voltage
251 end, coil 41 is tapped to withdraw the servo (sensing) signal
26¦ through a voltage divider comprising a pair of . serially
271 connected capacitors 46 and 47 of 200 pf each and a third
28¦ serially connected variable capacitor 48 of 50-900 pf which
291 is in turn connected to ground.
301 The common connection 49 of capacitors 48 and 47
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l leads to a rectifier voltage doubler 50 which is a dual
2 dlo~e 6ALS. Connectlon 49 ~s thus to the plate of one and
3 the cathode of the other diode, while the cathode of the
4 first is grounded and the plate of the other leads to a
filter circuit consisting of a 2.2 K ohm resistor 51 having
6 its end adjacent the plate by-passed the ground through a
: 7 115 pf capacitor 52 and its end remote from the plate by-
passed to ground through a .02 uf resistor 53. .-
. The common junction 54 of resistor 51 and capacitor
: l.O 53 thus has on it a negative DC voltage which is a function
l.l of the RF voltage at junction 49 in the voltage divider
1.2 comprising capacitors 46 and 47 and capacitor 48, rectified
- 1.3 and amplified by voltage doubler 50, Junction;.54 is connected
14 through a blocking diode 55 to crystal 56 and to the grid of
15 an oscillator tube 12 in exciter lO, which in the illustrated .
16 case is a 6Y6G. ¦
.~ 1 Oscillator tube 12 is also biased at the common
18 ¦junction 57 of diode 55 and crystal 56 by means of a voltage
l9 ¦divider consisting of a pair serially connected resistors
20 158 and 59 which are connected, respectively, between -llO
21 ¦volts DC and jun-ction 57 and between junction 57 and ground.
. 22 ¦Resistor 58 is 75 K ohm and resistor 59 is lO K ohm. An RF
. 23 ¦by-pass capacitor 60 having .005 uf is also connected from
24 ¦common junction 57 to ground. .
25 ¦ It will be apparent that variable capacitor 48
~ 26 ¦functions to control the amount of RF voltage impressed on
: 27 ¦voltage doubler and rectifier 50 and consequently to control
28 ¦the negative bias at terminal 54. Diode 55 prevents the
29 ¦flow of current from terminal 57 to terminal 54 when the
¦negative bias at terminal 54 is less negative.than the
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fixed negative bias supplied by the voltage divider formed of
resistors 58 and 59 and thus limits the maximum power output
of amplifier 20. When, however, the negative bias at terminal
54 goes below that at terminal 57 current flows from terminal
54 through resistor 59 to make the bias on tube 12 more
negative, and hence decreases the amplification in exciter 10.
This, of course, is a function of the capacitance of capacitor
48. Since the power output of amplifier 20 is a function of
the bias on oscillator tube 12, servo loop 40 thus, under the
control of the manual setting of capacitor 48, functions to
control and hold stable the power output of amplifier 20 by
controlling the voltage output of exciter 10 through control
of the amplification in oscillator tube 12.
It will be apparent, however, that should there be a
breakdown in the servo system oscillator 12 will be driven to
full amplification as determined by the fixed bias supplied by
resistors 58 and 59. As a consequence, a fail-safe circuit is
supplied, as shown diagramatically in FIG. 5. In this fail-safe
circuit the connection of AC supply 13 to the high-voltage DC
supply 14 for exciter 10 is made through a relay operated switch
15 which is normally closed. Switch 15 is operated to open
position by a relay coil 16 connected in series in the DC high
voltage lead 17 to the anodes of the amplifier tubes in
exciter 10. Coil 16 is shunted by an adjustable resistor 18
which functions to control the sensitivity of relay coil 16
and which is set such that, when the current flowing in line 17
exceeds a predetermined maximum, relay coil 16 will operate
switches 15 to open them and break the high voltage supply.
107Z186
Thus, if for any reason servo circuit 40 should fail
- or if for any other reason amplification in exciter 10 should
suddenly increase to an undesired value, the high voltage
supply 14 will be shut off and exciter 10 rendered inoperative,
thereby preventing the use of power amplifier 20 until the
difficulty has been located and switch 15 manually reset.
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 40C, 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 50C. In some instances the tumor tissue can be necrosed
at temperatures as ~ow as 46C. Destruction of the tumor can be
observed either by thermometric means, by X-ray techniques used
to sense the presence of the tumor, biopsy or 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
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107Z186
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 performation.
Other avascular lesions occurring in otherwise normal
tissue will response 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 unresectable 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 four inch applicators 30 described above, were
positioned one flat against the anterior and the other flat
against the posterior of his chest to position the tumor
between them. He was given general anesthesia and the applicators
30 were energized at a 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 the applicators 30. Conse-
quently, a skin burn resulted.
Three days later a thoracotomy was done to biopsy
the lesion. The entire tumor was incised and a large biopsy
taken. This biopsy was reported as inflammatory reaction
~;~
107Z186
only although the surgeon was sure he had incised the tumor.
Subsequently the patient's course has shown gradual improve-
ment. 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 cord approximately two years before treatment.
Approximately four months before treatment, the patient developed
a large mass the size of an orange (3" 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 stetched
and shiny; and the tumor had 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. 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 main-
tain 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
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~ ` I 107Z186 ~ .
} midaxilla, Thus in effect the patient's bod~ was positioned
betwee~ ~h~ ~wo applicators 30 such that the tumor was
3 located between them.
Power was initially raised gradually to 300 watts
(about 120 volts R.M.S. at 13.56 MHz) and maintained for 20
6 minutes between 275-300 watts.
7 One week later, the hard mass had become softer
8 and fluctuant in parts. Ten days after the treatment the
9 mass was aspirated and semi-liquid, necrotic material was
withdrawn. In order to further liquify the necrotic material
11 Bovine fibrinolysin and desoxyribonuclease were injected into
12 the tumor. Two days later, the tumor was again aspirated.
13 Nineteen days after the first treatment, the pat- -
14 ient was given a second treatment with the 4" applicators 30
15 again placed in the same manner except that the second
16 applicator was placed on the back of the chest to the right
17 of the midline. Treatment was for 20 minutes. Again the
18 power was gr~dually increased this time to 385 watts (135
.9 volts ~.M.S. at 13.56 M~z) and then varied between 350 to 410
20 watts during the ramainder of the therapy. -
21 Two wèeks later, the tumor was aspirated again.
22 Liquid~material was obtainèd and t~e tumor-had decreased-
23 considerably in size. No viable tumor cells were shown.
24 There were some autolyzed cells. The third treatment immedi-
ately followed such aspiration and was similar to the first
26 treatment except that initial power was 135 watts which was
27 increased to 235 watts (108 volts R.M.S. at 13.56 M~z) and
28 continued for a total of 11 minutes.
29 Although ~urther therapy was considered super-
30 fluous, since the tumor had already been destroyed, a fourth
: 107Z186
l ~ .,
1¦ treatment was given ten days later. In this instance,
2¦ applicators 30 were placed one on the ml~axllla, as descri~ed
above, and the other first to the right and then to the left
4¦ of the tumor. In each case, the skin was moistened with EKG
51 jelly and bronze wool sponge is placed against the skin
6¦ beneath the applicator 30 to maintain even electrical contac~t.
q ¦ The treatment was at 475 watts (150 volts R.M.S. ~t 13.56
.~ 81 MHz) on the left side for 20 minutes and at 375 to 400 watts
91 (138 volts R.M.S. at 13.56 MHz) on the right side for 20
lO¦ minutes.
11¦ The final pathological diagnosis indicated no
12¦ malignancy. The mass has almostlcompletely disappeared
13¦ although there is some inflammation and an ulcer under *he
14¦ site of the necrotic tumor.
~51 Before treatment in accordance with this invention -
16¦ the patient was having severe respiratory difficulty because
17 ¦the tumor was closing off his trachea just below the site of
18 ¦the tracheotomy. Since the treatment, the patient can
"~ ¦breathe freely and has had no respiratory difficulty. Ther-
20 lapy in accordance with this invention resulted in minimal
21 ¦necrosis of the stretched skin over the lesion which will
22 require-future--grafting.- -
23 ¦ Example III
24 ¦ In this case the patient had what was considered
2~ ¦to be a large, inoperable carcinoma of the lung which filled
26 the entire right upper chest. The tumor mass was larger
27 than the 4 inch applicators 30 which were available. One
28 applicator 30 was put on the anterior portion of the chest
29 wall after moistening the skin with conductive paste, and
3 the other applicator 30 was similarly positioned on the
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` ` 1072186
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 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 inflam-
matory reaction. The entire lobe was fixed and cut on alarge 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 ~umor
in the treated area was dead and undergoing autolysis.
In this case the inoperable carcinoma was consid-
ered 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.
--19--
` -'" 107Z186
The structure of the two applicators and energy feed
cables from the power source are structurally unique. Each
applicator 30 and its shielded coaxial cable 21 are designed
and constructed for use repeatedly in the operatingroom both
inside and outside the body cavity with necessary exposure to
contamination so as to require sterilization between uses. The
entire applicator-cable unit are one detachable unit entirely
encased in a continuous film of insulating resin such as
polyurethane of a thickness of about 14 mils. The unit hence
has a low dissipation factor for radiant energy passing through
` and are waterproof. During most uses a sleeve of bronze wool or
austenitic steel (18% nickel content) is placed over the
insulated disc applicators. This sleeve is about 1/2 to 1 inch
thick and compressible against the skin surface to reduce skin
and deep tissue reflectance and reduce scattering of the input
radiation. Since the metal sleeve is of a magnetic permeability
equal to the subadjacent tissue it does not itself absorb energy - -
- and heat up but serves to direct the wave deep into the body
cavity.
In the several preceding examples the frequency referred
to is preferably 13.56 megaHertz which is selected as a
convenient point within a broad band of from 100 kiloHertz to
about 200 megaHertz at which frequencies the wavelength is long
enough to control and penetrate with our particular apparatus.
The bronze wool control sleeve also eliminates "hot spotting" in
the tumor where parts of the tumor do not receive a uniform dose
of heat because of irregular contour on the skin surface caused
by ribs protruding etc. The non glossy coat of polyurethane
insulation is also critical to avoid eddy currents and skin
burn in cases where the skin may have residual salt thereon.
With an input of 500 watts for 30 minutes and long wave length
this factor of skin burn becomes of significance. In some cases
of tumors in difficult positions it is possible to move the
applicators a short distance back from the tissue surface to treat.
-2~-
'.
~07Z186
The insulating coating 35 should in any event be formed
of a dielectric material having a low dissipation factor, ie.,
below about 0.01. By dissipation factor reference is made to
the reciprocal of Q which is sometimes denoted by the expression
"tan" and is further defined as follows:
tan ~= " = Q
I = dielectric constant
~"= loss factor
.
Generally insulating materials suitable are glass and
mica which have dissipation factors of the order of 0.001 to 0.002,
polyethylene which has a dissipation factor 0.0002, polytetra-
fluoroethylene which has dissipation factors of the order of
0.002 to 0.006, polystyrene which has dissipation factors below
0.0002 and polyurethane which has a factor below 0.007 and of
the order of 0.005. The above noted dissipation factors are of
course frequency dependent and the values noted above are for
frequencies on the order of 107 Hertz. All of this relates to
the need to have low-loss insulating surfaces on tumor treating
applicators working in the 13-14 megaHertz range with high
wattage input required to give effective treatment to destroy
the tumor tissue. The polyurethane is of the thermosetting type
not the thermoplastic type which does not have the proper
dissipation factor.
