U.S. patent number 3,924,628 [Application Number 05/311,069] was granted by the patent office on 1975-12-09 for cyrogenic bladder for necrosing tissue cells.
Invention is credited to Paul E. Bingham, William Droegemueller, Ralph N. Eberhardt, Jr..
United States Patent |
3,924,628 |
Droegemueller , et
al. |
December 9, 1975 |
Cyrogenic bladder for necrosing tissue cells
Abstract
A method of, and apparatus for necrosing human tissue cells are
described in which an expandable bladder filled with a fluid at a
cyrogenic temperature is used to subject the entire area of tissue
in contact with the bladder to temperatures sufficiently low to
cause coagulation necrosis, whereby the entire contacted area of
tissue is simultaneously necrosed. As an example, this apparatus
can be utilized to cause sterilization by necrosis of the entire
functional endometrial layer of the uterus of a human female.
Inventors: |
Droegemueller; William (Denver,
CO), Eberhardt, Jr.; Ralph N. (Englewood, CO), Bingham;
Paul E. (Littleton, CO) |
Family
ID: |
23205251 |
Appl.
No.: |
05/311,069 |
Filed: |
December 1, 1972 |
Current U.S.
Class: |
606/21; 606/23;
607/105 |
Current CPC
Class: |
A61B
18/02 (20130101); A61B 17/42 (20130101); A61F
7/123 (20130101); A61B 2017/4216 (20130101); A61B
2018/0022 (20130101); A61B 2090/036 (20160201) |
Current International
Class: |
A61B
18/02 (20060101); A61B 18/00 (20060101); A61B
17/42 (20060101); A61F 7/12 (20060101); A61B
017/36 (); A61F 007/12 () |
Field of
Search: |
;128/303.1,401 |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Peter, Edward T. et al, "Technique of Gastric Freezing in the
Treatment of Duodenal Ulcer", J.A.M.A. 1819: 760-764. 1962.
128-303.1..
|
Primary Examiner: Pace; Channing L.
Attorney, Agent or Firm: Ferguson, Jr.; Gerald J. Baker;
Joseph J.
Claims
What is claimed is:
1. A method of effecting coagulation necrosis of the functional
uterine endometrium comprising the steps of:
a. inserting a flexible bladder in the uterus;
b. inflating said bladder with a fluid at cryogenic temperature so
that said bladder is in substantially continuous contact with the
inner surface of the functional uterine lining, said fluid
undergoing a phase change to extract heat from said functional
uterine endometrium; and
c. maintaining said bladder so inflated with said fluid at said
cryogenic temperature for a period of time sufficient for said heat
extraction to effect simultaneous coagulation necrosis of
substantially all of the functional uterine endometrium.
2. A method as defined in claim 1 wherein the exterior of said
bladder in contact with said lining is maintained at least
-73.degree.C for at least 2 minutes.
Description
DEFINITIONS
The following terms are used herein as having the meanings given
below:
"Necrosis" means the death of the cells in a tissue.
"Functional lining" of the uterus is that portion of the inner
lining of the uterus, the endometrium, to which an embryo might
attach. It excludes the portions of the uterine inner lining
forming the cervix, to which the embryo usually does not
attach.
"Cryogenic" as an adjective is used to refer to temperatures
sufficiently low to cause cell necrosis.
BACKGROUND OF THE INVENTION
The use of instruments at extremely low or cryogenic temperatures
to treat the human body is referred to as "cryosurgery" within the
medical profession. In cryosurgery, an instrument cooled to a very
low temperature is brought into contact with body tissue and the
contiguous or adjacent cells are destroyed by the cryogenic
temperature, a result known also as coagulation necrosis. The
destruction of a cell is usually effected by the formation of ice
within a cell, which is sufficient to kill or irreversibly damage
it. It can normally withstand ice formation outside the cell wall;
to destroy the cell, ice must be formed inside the cell
membrane.
A human cell contains both salt, most abundantly sodium chloride,
and water. As the external environment of the cell is cooled, a
cell protective mechanism operates to resist internal freezing of
the cell. Water is expelled from within the cell through the cell
membrane. The expelled water may freeze without permanent damage to
the cell, but this protective mechanism results in increasing the
saline concentration within the cell, lowering its freezing point
and rendering it more difficult to destroy with low temperatures.
This process continues, with external ice formation, until the
eutectic temperature of the sodium chloride, -21.2.degree.C, is
reached. At this temperature ice is formed within the cell and it
is effectively destroyed.
Therefore, in light of the above, cryogenic destruction of a cell,
or of the tissue which is formed of the cells, requires either (a)
bringing the interior of the cell to a point below the eutectic
temperature of sodium chloride or (b) reducing the cell temperature
very quickly so that the cell protective mechanism cannot cope with
the temperature change and the cell does not have time to expel
sufficient water through the membrane to render its interior
solution freeze resistant. In cryogenic necrosis then, the
variables are the absolute temperature to which a cell is brought,
the rapidity of cell temperature change, and also, not discussed
above and imperfectly characterized as yet, the length of time a
cell is kept at a specific temperature.
Cryosurgical techniques, utilizing cryogenic necrosis, have been
used in gynecology for the treatment of chronic cervicitis and
dysfunctional uterine bleeding by applying an instrument at
cryogenic temperature to the affected area.
Present procedures for permanent sterilization of the human female
involve major surgery to enter the abdominal cavity. The attendant
disadvantages are obvious and are those of most surgical
procedures: the inconvenience and cost of a hospital stay; and the
high cost of services of a surgeon and other professionals.
It is the object of this invention to make available less expensive
sterilization of human females by providing a sterilization
procedure that may be performed more quickly than present surgical
sterilization techniques and will not require the attendance of an
entire surgical team or their support facilities.
The inner lining of the uterus comprises a layer of endometrium
that varies in thickness from 2 to 8 millimeters, and outward from
the endometrium is a layer of myometrium, or muscle tissue. After
conception, the embryo attaches itself to the inner wall or surface
of the uterus at some point on the functional lining and is
supported and sustained by the endometrium. By substantially
destroying the entire endometrial layer throughout the extent of
the functional lining of the uterus by cryogenic necrosis, that
layer is not capable of sustaining an embryo. An article, entitled
"Destruction of the Endometrium by Cryosurgery," by W.
Droegemueller, E. Makowski and R. Macsalka, appearing in the
American Journal of Obstetrics and Gynecology, Vol. 110, No. 4,
June 15, 1971, describes cryogenic necrosis of the uterine
endometrium.
The method used to date, however, and described in that article,
comprised use of a metal probe having a rather small operative area
to successively freeze relatively small areas of the endometrium,
eventually covering the entire functional lining. That process was
relatively slow and laborious and considerable painstaking effort
was required to insure that the entire functional lining was
necrosed. The method and apparatus of this invention overcome these
disadvantages by providing for cryogenic necrosis of the entire
functional uterine endometrium in one application and with complete
coverage. A flexible bladder is inserted into the uterus and
cryogenic fluid at slightly above atmospheric pressure is
circulated through the bladder, expanding it into contact with the
entire inner uterine surface and at the same time removing heat
from that surface so as to effect coagulation necrosis of the
endometrium.
The nature of the inventive method and apparatus is set forth in
greater detail in the description below taken in conjunction with
the drawings, which form a part of the specification, and in
which:
FIG. 1 shows in a partially schematic manner a sterilization system
suitable for use with liquid nitrogen as a refrigerant;
FIG. 1a is a partial sectional view taken approximately along line
1a -- 1a of FIG. 1;
FIG. 2 shows an alternative method for pressurizing the liquid
nitrogen system of FIG. 1;
FIG. 3 shows schematically a sterilization system suitable for use
with refrigerants that are stored at high pressure;
FIG. 4 shows an alternate arrangement for storing and supplying the
high pressure refrigerant in the system of FIG. 3;
FIGS. 5a and 5 b show alternative probe expansion orifices suitable
for use with the high pressure refrigerant system of FIGS. 3 and
4;
FIGS. 6a through 6e show the insertion sequence of one possible
probe package.
FIG. 1 shows a uterus 10 distended by an inflated bladder 11
attached to a probe generally indicated as 12. The system uses as a
refrigerant liquid nitrogen 13 contained in a Dewar vessel 14 that
is closed with a plug 15. The liquid nitrogen and the vaporized
gaseous nitrogen that fills space 16 above the liquid in Dewar
vessel 14 would normally increase in pressure due to heat
conduction through the Dewar vessel walls causing liquid nitrogen
to vaporize. A vent valve 19 connected to pipe 18 is made such that
when pressure in the Dewar vessel exceeds a specified value the
valve opens to vent the excessive pressure. In this manner the
pressure within the Dewar vessel 14 is controlled to be less than
or equal to any preset pressure. As long as liquid nitrogen exists
in the vessel, heat conduction into the liquid nitrogen will cause
the vent valve 19 to slowly vent vaporized nitrogen to the
atmosphere, maintaining pressure in the Dewar at the specified
operating pressure. This pressure is used to force the refrigerant
into probe 12. Adequate pressure is maintained in the Dewar
throughout the expulsion of all of the refrigerant by causing vapor
space 16 to be approximately one-half of the total Dewar volume. As
refrigerant is forced from the Dewar, vapor in space 16 expands to
a lower pressure until it reaches approximately one-half the
original pressure that existed at the initiation of refrigerant
flow. Vent valve 19 also provides conventional protection by
venting any excessive pressures that should build up through some
malfunction.
Pressure in excess of atmospheric applied to the surface of liquid
nitrogen 13 forces it up into vertical pipe 20, through valve 17
and flexible tubing 21 and into supply tube 22 of probe 12. In the
course of passage through these tubes, the liquid nitrogen
evaporates and forms gaseous nitrogen. The nitrogen fluid emerges
from orifice 23 at the end of supply tube 22 and flows into bladder
11, forcing it to expand into contact with the inner surface of
uterus 10. The cold nitrogen gas absorbs heat from bladder 11 and
then flows through ports 24 into return tube 25 and is vented to
the atmosphere at the open end 26 of tube 25. The arrows in FIG. 1
indicate the flow of nitrogen in probe 12. Supply tube 22 and
return tube 25 are rigid or semi-rigid coaxial tubes. The passage
of return tube 25 surrounds supply tube 22 and bladder 11 is
attached to the outside surface of tube 25 by a suitable low
temperature cement. The end of supply tube 22 is open to the
interior of bladder 11 by virtue of orifice 23, and that end of
return tube 25 is closed by being joined to the periphery of the
end of tube 22. The size of orifice 23 may be quite large, in
relation to the diameter of tube 22, since only low pressure gas is
being fed through it and it does not act as an expansion orifice.
Ports 24, comprising the only openings into return tube 25 or the
inside of bladder 11, are located well back from the end of the
tubes in order to force the nitrogen expelled from orifice 23 to
circulate and absorb heat from bladder 11 before being vented to
the atmosphere through return tube 25.
The probe 12 and its attached bladder 11 must be sufficiently
small, when the bladder is deflated and furled around tube 25, so
that it can be conveniently inserted into the uterus through a
partially dilated cervix. The bladder should be inflated to a
pressure sufficient to insure firm contact with the tissue to be
necrosed, for example, the interior uterine surface, but should
preferably be maintained at about 2 or 3 p.s.i. to avoid any
possible risk of internal injury to the patient. It has been found
that maintaining a pressure in the Dewar of between 5-10 p.s.i.
results in adequate flow of the nitrogen and the maintenance of
proper bladder pressure, although the precise to be used in any
case will, of course, need to be adjusted as a function of the
various system parameters.
In the system described above, the liquid nitrogen vaporizes in the
course of its flow from the Dewar 14 to its exit into bladder 11 at
supply tube orifice 23. However, the system may alternatively be
operated by permitting the nitrogen to emerge from orifice 23 as a
liquid, and allowing it to vaporize in bladder 11.
Bladder 11 must be capable of withstanding cryogenic temperatures
without rupturing, and should have as good heat transfer
characteristics as obtainable in such materials to provide
efficient freezing action. A bladder molded of a heat curing rubber
bearing General Electric identification SE-5553 has been found
satisfactory.
Testing conducted to date indicates that with the system shown in
FIG. 1, the exterior surface of the bladder when completely
enclosed in a warm liver reached -73.degree.C within five minutes
from the start of circulating the nitrogen in the bladder. Based on
prior medical testing, at this temperature complete cell necrosis
would occur within 2 to 4 minutes. This causes sterilization to be
effected.
FIG. 2 shows alternative methods of providing the required
pressurization of the Dewar in the system of FIG. 1 in which liquid
nitrogen is the refrigerant. Instead of allowing the Dewar to
become pressurized due to heat conduction, as shown in FIG. 1, one
alternate method that may be used to pressurize the vessel 14 is an
external source of pressure 52 which is connected with vertical
pipe 18 through pipe 51. Pipe 18 feeds down through plug 15 and
pressurizes the Dewar 14. Vent valve 19 provides conventional
protection by venting the Dewar 14 to the atmosphere should
excessive pressure build-up through some malfunction.
A second alternative method of providing the required
pressurization of the Dewar 14 is also shown in FIG. 2. Instead of
applying an external pressure to the Dewar, the vessel may be
pressurized by energizing a heater coil 28 that is submerged in the
liquid nitrogen 13 by means of a source of power 29 via wires 30.
The heat generated by the coil causes the liquid nitrogen to
vaporize and the vessel pressure accordingly increases and forces
the liquid nitrogen through the pipe 20 and tubing system and into
the probe 12.
FIG. 3 is a schematic diagram of another system embodiment in which
slightly different type of refrigerant is used, that is, a high
pressure refrigerant, rather than the liquid nitrogen of the FIG. 1
embodiment which is maintained at atmospheric pressure in a Dewar
vessel as described above. The high pressure refrigerants, on the
contrary, are stored at high pressure in liquid form in non-vented
bottles of high strength. The liquid boils away until the vapor
pressure in the bottle is equal to the saturation pressure; the
refrigerant then is stored as a liquid at room temperature under
its own vapor pressure, so that no Dewar vessel is necessary. Freon
13 and Freon 23, supplied by Dupont, and nitrous oxide, are
refrigerants useful for this system in the embodiment shown in FIG.
3. The Freons have a vapor pressure in the neighborhood of 500
p.s.i. and nitrous oxide, in the neighborhood of 700 p.s.i. at room
temperature. Liquid nitrogen, on the other hand, is not suitable
for storage at room temperature because its vapor pressure is so
high that providing storage containers of sufficient strength is
not feasible.
In FIG. 3 a bottle 32 is shown containing both a liquid refrigerant
33 such as Freon or nitrous oxide and gas 34. To operate the
system, outlet valve 35 is opened and the high pressure gas is
forced through line 36, through a three-way valve 37, and through
line 38, into probe 39. Lines 36 and 38 preferably include sections
of flexible hose. When the high pressure refrigerant gas reaches
probe 39 it is emitted from a small expansion orifice or nozzle and
the resulting gaseous expansion causes the cooling. Probe 39, which
is merely indicated schematically in FIG. 3, is similar to the
probe described in connection with the embodiment of FIG. 1
including the bladder, except that it is provided with expansion
orifices, as shown in FIGS. 5a and 5b, rather than with the rather
large supply tube orifice 23 shown in FIG. 1. This is necessary
because the nitrogen of the FIG. 1 embodiment is already at
cryogenic temperature since it is stored at cryogenic temperature,
and cannot lose any heat through expansion on going from high to
low pressure, since it is already at a low (substantially
atmospheric) pressure. The high pressure refrigerants of the FIG. 3
embodiment, however, since they are stored at room temperature,
must obtain their cooling from the expansion of the gas as it is
emitted from a high pressure line through a small expansion orifice
into the low pressure interior of bladder 11.
FIG. 5a shows a small single expansion orifice 41 located in the
end of supply tube 22 and suitable for use in the probe 39 of the
high pressure embodiment of FIG. 3. Instead of the single orifice
of FIG. 5a, multiple expansion orifices 42, as shown in FIG. 5b,
may alternatively be used. As examples of the sizes of orifices
suitable for the systems described, an orifice 23 of 0.070 inch has
been found suitable for the liquid nitrogen system of FIG. 1. In
the high pressure system of FIG. 3, the single expansion orifice
(41 of FIG. 5a) of 0.0135 inch has been used for both nitrous oxide
and Freon 13 and Freon 23. Two 0.0135 inch expansion orifices (42
of FIG. 5b) or, alternatively, a single orifice (41 of FIG. 6a) of
0.024 inch have been used with both Freons.
The three-way valve 37 is used in connection with the warming of
the bladder 11 after the cryogenic necrosis has been effected and
prior to removal of the instrument from the uterus. Human tissue is
in large part water and when it is in contact with any object at a
temperature below the freezing point of water it sticks to the
object by freezing to it, and will tend to tear if the object is
pulled away. For this reason, after the cryogenic or freezing cycle
of probe 12, in both the embodiments of FIGS. 1 and 3, bladder 11,
which is configured to contact substantially the entire area of
tissue to be necrosed, must be warmed before it can be removed, so
that the contacted tissue is not torn.
In the liquid nitrogen embodiment of FIG. 1 the warming is
accomplished by stopping the flow or circulation of cryogenic
nitrogen into probe 12 and permitting the heat of the patient's
body to bring the bladder temperature up. In the high pressure
embodiment of FIG. 3, the action of body heat in warming bladder 11
is assisted by circulating room temperature gas through the
bladder. This is accomplished by moving the three-way valve 37. The
valve, as shown schematically in FIG. 3, is in a position to pass
the refrigerant gas from line 36 directly to line 38. By rotating
the valve 37 one quarter turn in the counter-clockwise direction as
shown in FIG. 3, the gas from line 36 will be diverted by valve 37
down into a regulator 43, which may be a Norgren Company Model
11-010-084. Regulator 43 reduces the pressure of the gas to about
50 p.s.i. and then feeds it on through line 38 to probe 39. The gas
flows through expansion orifices 41 or 42, but since it is already
at a very low pressure, there is hardly any expansion or cooling,
and the relatively warm gas flowing through the interior of bladder
11 hastens its warming.
FIG. 4 illustrates an alternative refrigerant feed arrangement for
the high pressure embodiment of FIG. 3 wherein some additional
cooling capacity is obtained. A high pressure storage bottle 44 is
shown in an inverted position, so that its outlet, and the
associated outlet valve 45, are located at the bottom of the
bottle. In this embodiment liquid refrigerant, rather than gas, is
fed from the bottle. This change of state from liquid to gas
provides some additional cooling to that obtained by the gaseous
expansion during emission from the probe expansion orifices.
The bladder material SE-5553 supplied by General Electric and found
satisfactory for the embodiment of FIG. 1 is also satisfactory for
the FIG. 3 embodiment, where the refrigerant temperaturees are not
nearly as low: nitrogen boils at -320.4.degree.F; nitrous oxide at
-129.1.degree.F; Freon 13 at -114.6.degree.F and Freon 23 at
-115.7.degree.F. In addition a dispersion coating rubber supplied
by Dow Corning to their number 92-009 has been found satisfactory
for use with the high pressure (and higher temperature)
refrigerants of the FIG. 3 embodiment. Bladders of approximately
0.020 inch thickness have been found satisfactory. Various methods
of fabricating the bladder may be employed, but one method found
satisfactory has been to lay up the bladder in successive thin
layers upon a mandrel. This method of fabrication also facilitates
placing one or more thermocouples 50 (FIG. 1a) in the bladder. The
thermocouples 50 and their leads may be placed between successive
layers as the bladder is formed. Such thermocouples are connected
to appropriate instrumentation for monitoring bladder
temperature.
The embodiments of FIGS. 1 and 3 each have advantages and
disadvantages so that neither can clearly be preferred to the
other. The liquid nitrogen refrigerant of the FIG. 1 embodiment
provides a much lower temperature and consequently faster tissue
freezing. It, however, has the disadvantages of imposing more
constraints upon system components, especially the bladder, because
of the lower temperature, and it requires the inconvenience of low
temperature refrigerant storage. The high pressure refrigerants, on
the other hand, useful in the FIG. 3 embodiment, are conveniently
stored at room temperature, are generally more readily available
than liquid nitrogen, but compare unfavorably with liquid nitrogen
in having higher temperatures and consequently slower freezing.
In using the cryogenic system of either FIGS. 1 or 3 to sterilize a
female, the procedure is as follows. The cervix is visualized and
then grasped with a tenaculum. Then the cervix is dilated with
instruments to approximately one centimeter. Then probe 12, with
bladder 11 furled tightly around it, is inserted through the cervix
into the uterus. The refrigerant is applied to probe 12 for a
sufficient period to accomplish cryogenic necrosis of the
functional endometrium. The bladder 11 is then warmed and
removed.
FIGS. 6a through 6e shows in sequential steps the application of
one configuration in which either of the embodiments of FIG. 1 or
FIG. 3 may be packaged: a tampon-type cartridge. FIG. 6a shows the
package, comprising a "handle" portion, which is comprised of
supply tube 22 and return tube 25, the bladder 11 furled tightly
around the end of return tube 25, and encased in a cylindrical
sleeve 48 terminating in an annular shoulder 49. The outside
diameter of the sleeve should be less than one centimeter so that
it may be readily inserted into the partially dilated cervical
opening.
FIG. 6b shows the sleeve 48 containing the furled probe being
inserted into the opening in the cervix 55. In the next step, shown
in FIG. 6c, sleeve 48 has been fully inserted into the cervix 55,
being stopped by the abutment of the sleeve shoulder 49 against the
outer cervical surface. Also in FIG. 6c, the probe has been
advanced so that the end of the probe with the furled bladder 11
has been pushed free of sleeve 48 and is positioned inside the
uterus. When the refrigerant is applied to probe 12, bladder 11
inflates and assumes the position inside the uterus shown by FIG.
6d, showing a view along a vertical plane through the body, and
FIG. 6e, showing a view along a horizontal plane through the
body.
The primary feature of the package of FIG. 6 is the use of the
flanged sleeve 48. This sleeve, which is preferably about 2.5
centimeters in length, is used to protect the bladder from
mechanical damage during storage and handling prior to use and also
as an insertion aid. Since the inner uterine surface within about
2.5 centimeters of the cervix opening is not part of the functional
uterine lining and should not be necrosed, the insulating effect of
the sleeve will protect this portion of the uterus and prevent an
unnecessary loss of cooling capacity.
While certain illustrative embodiments and details thereof have
been set forth herein, various changes and modifications thereto as
will occur to those skilled in the art may be made without
departing from the scope of the invention, which is defined only in
the appended claims. For example, although the embodiments of the
invention have been described in detail in connection with the
female sterilization application, it should be appreciated that by
appropriately configuring the bladder, tissue other than the
uterine lining tissue can be necrosed and the uterus lining or a
portion thereof may be necrosed for purposes other than
sterilization such as for treating dysfunctional uterine
bleeding.
* * * * *