Note: Descriptions are shown in the official language in which they were submitted.
33~
This invention relates to hyperthermia, and
more particularly to impro~ed method and apparatus for
efecting hyperthermic treatment specifically for the
; purpose of retarding the growth of growing cancer cells.
S There is mounting evidence that the application
of heat within the range of 41.5C to 43.0C can be used
effectively to retard the growt}. of cancer cells.
Recent interest in this subject has intensified
to the extent that an XnternatiGnal Symposium on Cancer
Therapy by Hyperthermia and Radiation was held in
. .
~ - 2 -
~4~37
Washington, D.C. in April of 1975 under the joint sponsorship of
The National Cancer Institute of the ~.S. Public Health Service
and The American College of Radioloyy, in cooperation ~ith the
[Iniversity of Maryland School of Medicine.
Tlle Proceedings of this symposium are transcribed in a three
hundred and four page ~olume containillg many articles dealing
with varied aspects of hyperthermia and cancer. These articles
and the cited references thereof represent a cornpreherlsive
listing of available literature publications.
Other articles of interest since 1975, the date of the
symposium are as follows:
Hofer, K.G., Choppin, D.A. and Hofer, M.G.: EXfect of
~-lyperthermia on the Radiosensitivity of Normal and ~lalignant
Cells in Mice. Cancer, 38:279, 1976.
Larkin, ~.M., Edwards, W.S. and Smith, D.E.: 'i'otal 13Ody
Hyperthermia and Preliminary Results in i~uman Neoplasmus. Surg.
Forum, 27:121, 1976.
Wheldon, ~.E.: Exploiting Heat Sensitivity of Leukemic
Cells. Lancet, 1:1363, 1976.
- 20 Hyperthermia in the Treatment of the Cancer Patient.
Cancer, 37:2075-2983, 1976.
Much of the above literature includes reports to tile effect
that hyperthermia utilized in a range of
33~7
temperatures between 41.5C and 43.0C causes specific
anti-cancer effects when used either as a primary or
adjuvant agent against a wide spectrum of malignant disease.
The literature indicates that hyperthermia has been shown
to induce cytotoxicity in sarcoma and melanoma cells in
tissue culture (Stehlin et al.) and strongly enhance anti-
tumor effects of irradiation in vivo of L-1210 and Erlich
ascites cells (Hofer et al~). The addition of hyperthermia
to regional perfuslon chemotherapy of me:Lanoma resulted in
an increased lncidence of tumor con~rol and patient survival
without increased adverse effects (Stehlin e~ al.). Employed
as a systemic agent, hyperthermia ~nduced objective regression
in 13 of 18 (70%) patients with dissemlnated disease resistant
to other therapy, 9iX of whom were surviving 11 to 22 months
~ post treatment (Larkin et al).
; Experimental work undertaken in contemplation of
the present invention indicates the efectiveness of hyper-
thermia against systemic dlsease may be even greater than
indicated by Larkin et al. Although the levels of hyper-
thermia employed by Larkin et al. ~approximately 42.0C)
were adequate, the period of application was only five hours.
Moreover, the procedures undertaken to effect the hyper-
thermic treatment would indicate that a stable temperature
}evel of 42C was not maintained systemically for five
hours. Larkin et al. employed insulating sheets and liquid
- 4 -
~ f~ 3'7
heatin~ blankets surrounding the patients for heat appli-
cation. Due to the relatively poor conductivity of the skin
and the further adverse effect to conductivity of profuse
sweatinq, elevated systemic te~peratures cannot be rapidly
induced. Moreover, this adverse co~ductivity condition
can be expected to maintain the existence of large tem-
perature differentials throughout the system. For example,
blanket control temperatures of 120F (48.89C) ~ere
utilized, a lethal systemic level.
Based upon the analysis of the type of problems
enunciated above which are evident from the systemic pro-
cedures and devices heretofore proposed and utilized, a set
of desirable criteria Eor method ancl devices for effecting
hyperthermic treatment can be listed as follows:
1. Systemic temperatures of 41.5 to 43.0C
induced.
2. Selected ~emperatures ob~ained within one hour.
3. Hyperthermia maintained for 24 to 48 hours.
4. Fine temperature control and potential auto-
regulation of temperature possible.
5. A rapid cooling as well as a heating effect
readily achieved.
6. General anesthesia unnecessary or required
for only a brief period.
7. Patients undergoing hyperthermic treatment
3~7
maintained in a setting conduct:ive to conventional
caxe.
8. H~perthermla possible in diverse settings
such as radiation therapy or isolation areas.
9. Repetitious induction of courses of
hyperthermia over a several day period possible.
10. Hyperthermia lnduced with reasonable safety
in neutropenic or thrombocytopenic patients.
It is an object of the present invention to provide
a method and apparatus for effecting hyperthermic treatment
which will meet the above-listed desirable criteria. In
accordance with the procedural principles of the present
invention, this objective is obtained by establishing a
s~erile extr~corporeal flow path for blood having an inlet,
an outlet and a temperature control zone therebetween,
establishing communication of the inlet of the extracorporeal
flow path with the patient's bloodstream so that blood can
be withdrawn and supplied to the extracorporeal flow path
without adversely affecting the bloo~ depleted areas from
which the blood is withdxawn, establishi~g co~.lunication of
the outlet of the extracorporeal flow path with the patient's
bloodstream so that blood flowing from the extracorporeal
flow path is returned to the bloodstream in such a way as
to be distributed systemically, pumping blood withdrawn from
the patlent's bloodstream along the extracorporeal flow path
through the temperature control zone at a controlled rate
and return ng the same to the patient's bloodstream to be
distributed systemically, as aforesaid, controlling the
temperature o the blood flowin~ along the extracorporeal
flow path through the temperature control zone for ~n initial
period during which the ~emperature level of the blood within
the zone is raised without subjecting the same to localized
temperatures in e~cess of approximately 45 C so that the
systemic distribution of the returned blood gradually in-
creases the core temperature of the patient's body to a
generally stable temperature condition at a lcvel of ap-
proximately 41.5C, but not higher than appro~imately 42.5C,
and maintaining control of the temperature of the blood
flowing along the extracorporeal flow path through the
temperature control zone at the generally stable temperature
condition for a second time period sufficient to retard the
growth of cancer cells.
It is recognized that extracorporeal heating of
blood for anti-cancer purposes has been undertaken in regional
perfusion practices. Procedures of this type are discussed
by Cavaliere et al. and Stehlin and are to be distinguished
from the systemic hyperthermia induced by the present pro-
cedures, as indicated above. In these regional perfusion
~ practices, the main femoral artery and vein are temporarily
; 25 occluded by vasoular clamps or tourniquets and a closed
7 -
.
. ..
extracorporeal system is established, solely within the
femoral extremity. In ~his extracorporeal circuit, heat is
ayplied as an adjunct to the other treatments, such as
chemotherapy, w}lich are utilized in the regional circulating
S system. This system neceScitates the utilization of oxy-
genating equipment o~ a ty2e similar to that used in open
heart surgery. As is evident from the known time liml-
tations imposed upon open hear~ surgery by virtue of the
utili~ation of oxygenating equipment, the time frame ~ithin
which such combined oxysenating and heating treatments can
be continued even on a regional basis without imposing at
least a percentile permanent dal~age to the blocked femoral
areas of the patient is quite limited.
Pettigrew, in re~erring to these regional per-
fusion practices as background to his preferred combined hot
wax bath and heated respiratory gases procedure fo. inducing
total body hyperthermia, appears to consider the regional
perfusion procedures to be applicable to induce both reg-
ional hyperthermia as well as total bGdy hyperthermia,
perhaps by analogy to the open heart e~:~racorporeal shunt-
ing. (Induction of Controlled Hyperther~nia in Treatment of
Cancer, Henderson, M.A. and Pettigrew, R.T. Lancet, 1:1275,
1971 and Cancer Therapy by Whole Body Heating, Pettigrew,
R.T. Proce~edings, p. 282). The P~ttiqrew Lancet article
characterized the reyional perfusion ~ork of Cavaliere et
al. ("Selective Heat Sensiti~ity of Cancer Cells", Cancer,
B37
1967, 20-1351) as having "achieved very satis~actory tem-
peratures in the malignancies using an arteriovenous shunt
and a heat exchangar, but since ~his requires surgery it
cannot be repeated indefinitely and can only be applied
easily to peripheral malignancy."
It is of significance, however t to note that the
recognized practitioners of regional perf~lsion, namely
Cavaliere et al. and Stehlin et al., have both indicated
that the regional perfusion pract.ices utilizing a shunt and
an extracorporeal heat exchanger are limited to regional
extremity applications and both have utilized other pro-
cedures for inducing total body hyperthermia.
On page 135 of the cancer article Cavaliere et al.
state:
"This method of high temperature
treatment obviously has limitations
and at pre~ent is indicated ln patients
with primary or recurrent malignant
tumors of the limbs for whom the only
alternative therapy would be amputation,
which often does not prevent me~astases~
... It is evident that future progress in
this field will come ~rom total-body
high-temperature treatment~ We are
now in the process of developing tech-
niques towards this end, which are
considerably different from those now
being used."
The last paragraph of the Stehlin article in the
Proceedings publication, page 271, sets forth the ~ollowing:
.~ 3~7
"As a result of our experience with
regional perfuslon with heat, we are
currently, and have for the past five
years been investlgating the possi-
bility that syqtemic hyperthermia
induced with bacterial toxins will
enhance the antitumor effects of
various chemotherapy agents on
melanomas and sarcomas~"
~ preferred minimum flow rate in accordance
with the principles of the present invention, is approxi-
mately 1 liter per minute. Such flow rate can be achieved
by following the procedures of the present invention with-
out affecting the femoral areas from which the blood i~
withdrawn, Thus, with the present procedure, there is no
systemic femoral isolat~on as by a clamp or tourniquet
occluding the main femoral artery and vein, but rather, a
preerred procedure is to effect communication of the
extracorporeal flow path between the famoral artery and
the femoral vein through a side wall of each, so that
systemic circulation in the femoral areas can continue.
The pumping proceduxe undertaken to effect flow of the
withdrawn blood through the temperature control zone of
the extracorporeal flow path achieves an adequate con-
trolled flow rate while permitting adequate systemic cir-
culatory flow through the femoral areas sufficient to
prevent the type of adverse e~fects over extended periods
of time which will occur in the aforesaid regional per-
fusion techniques.
-- 10 --
. ~
~4~ 7
The present invention also contemplates an
improved implantable de~ice for facllitating the connection
of the ex~racorporeal flow circuit with the blood system of
the patient. Devices for establishing an extracorporeal
blood flow path for the purposes of kidney dialysis as
distinguished from systemic hyperthermic treatments are
well-known. These devices, known as shunts, are made
commercially available by several manufacturers. Typically,
these shunt devices are implanted in the patient and
include tubes which extend extracorporeally. ~hese exterior-
ized tubes have caused considerable dif~iculty.
A good discussion of the difficulties encountered
in the practice3 relating to such exteriorized shunt de~
vices is contalned in UOS. patent No. 3,998,222. In the
opening paragraphs of the specification, one type of shunt
device is described as a U-shaped loop, one end of which
is connected to a vein and the other end of which is con-
nected to an artery. The loop itself is implanted sub-
cutaneously but outlet conduits extending from the sides
o the loop protrude through open holes in the skin to
outlet terminals on the outside of the body. Removable
plugs fit in the outlet tubes and block the flow through
these tubes during normal conditions. When the patien~ is
sub-jected to dialysis, the plugs are removed and the out-
let terminals are connected to inlet fittings for a
dialysis machine~ (See 3,826,257).
83~
One of the problems enunciated in the opening
paragraphs o the specification attributable to this type
of exteriorized shunt is the ri~k of infection in the
location where the outlets protrude ~hrough the opening
holes in the skin~ While there is considerable reference
to problems relating to blood clotting in shunt devices
of the prior art, there is proposed in the patent a shunt
arrangement which would at least have the effect of al-
leviating the infection problem~ in that the shunt device
of the invention is arranged to be implanted in a com-
pletely interiorized or totally subcutaneous condition:
In order to effect communication of the totally interiorized
shunt device with the extracorporeal flow path, the im-
planted device is provided with mechanically movable valve
members. These valve members are normally retained in a
position within housings provided by the shunt device
which maintain the valve members out of communicating re-
lation with the blood flow through the shunt device. The
valve members are provided with cooperating surfaces such
as square apertures or threads which are operable to
initially establish a fluid~tight communication with a
hollow needle. The hollow needle is thus capable of being
inserted through the skin into fluid contact with the
' valve member and then after such fluid coupling has been
effected, the hollow needle is capable of effecting the
;,
X - 12 -
:
83~
movement of the valve member into flo~ communicating re-
lation with the bloodstream.
While the patent describes the utili~ation of a
Fogarty catheter for effecting the cleaning and declotting
5 o the device, no provision is made for preventing the
clotting of the blood within the central flow passages of
the valve members when they are disposed in their normal
closed positions. Moreover, while provision is made for
circulating blood between the periphery of the valve membexs
and the housing retaining the same when the valve members are
in their opened position, no such provision is made or the
- valve members when they are in closed position and, indeed,
the peripheral passages provided for continued ~low when the
valve members are open are themselves closed when the valve
member is closed, thus presenting, along with the interior
passages o the valve members, spaces where blood would be
trapped and become clotted.
While it is recognized to be desirable to overcome
the disadvantages of the commercially available exteriori~ed
shunt device, the arrangement disclosed in ~he aforesaid
patent would ~ppear to present clotting problems equal to,
if not worse than the clottiny problems noted in the prior
art. When it is considered that it is quite usual for
cancer patients to be hypercongulable, the clotting
problems of the prior art assum~ greater proportions
.
- 13 -
3~7
when contemplatillg the utilizatlon of such shunts for
hyperthermic treatment of a patient for anti-cancer pur-
poses. Moreover, effective hypert~,~rmic treatments in
accordance l~ith the principles of ~he present invention
require flow rates considerably in excess o that normally
provided for kidney dialysis.
Accordingly, it is a further object of the pxesent
invention ~o provide a shunt device of the totally sub-
cutaneous type which is particularly suitable for use in
hyperthermic treatment of a patient for anti-cancer pur-
poses in accordance with the present invention, which
device overcomes, or at least substantially alleviates,
the clot',ing problems of the prior art heretofore noted.
This objecti.ve is obtained by providing a totally
lS subcutaneous implant for use with the apparatus provi~ing
the extracorporeal blood flow path~ including both a blood
withdrawing and a blood returning percutaneous cannula,
each of which is cooperable with a trocar for effecting
the percutaneous disposition thereof, which cannulas co-
operate with the implant ~o achieve the extrac rporealblood flow. The implant comprises a body of elastomeriC
material adapted to be implanted totally subcutaneously
in a femoral extremity, the body having an arterial pas-
sage therein, a spaced venous passage, and a bypass conduit
extendil~ ~rom one end of the arterial passage to one end
- 14 -
37
of the venous passage. An arterial tube and a venous tube
of vascular prosthesis material are provided, each having
one end connected in commw~icating relation with the other
end of the respective ar~erial or venous passage anA an
opposite end ad~ted to be connecte: with a respective
main ~emoral artery or vein side wall in communicating
relation respectively with the respective interior of the
femoral artery or vein.
The elastomeric body is provided with means extend-
ing from two spaced positions exterior of said elastomeric
body inwardly thereof to two positions in communicating
relation respectively with the arterial and venous pas~
;~ sages operable to move in response to the insertion of a
cannula-trocar assembly from (1) a closed condition ex-
cluding fluid containing space within the body between the
~, respective two positions so that blood flowing ~rom the
arterial tube through,the arterial passage will pass there-
~rom through the bypass conduit into the venous passage
and out of said venous tube into (2) an open condition
2~ excluding fluid receiving space within the body from the
exterior periphery of the.portions of the respective
cannula extending between the two respective positions
each of which also extends percutaneously and in com-
municating relation with the respective arterial or
: 25 venous passage so that blood flowing from the arterial
-- 15 --
i 337
tube throu~h the arterial passage ~ill flow through the
bypass conduit as aforesaid and, in addition, will also ~low
into the blood withdrawing cannula (with its trocar re-
moved), through the ex~racorporeal flow path, through the
blood retw ning cannula (with its trocar removed), back into
the venous passage.
A further object of the present invention is the
provision of an implant device of the type described which
is simple in construction, economical to manufacture and
eff~ctive in operation.
Another object of the present invention is the
provision of cannula-trocar assemhlies particularly con-
structed to cooperate with such implant, which cannula-
trocar assemblies are simple in construction, economical
to manufacture and effective in operation.
These and other objects of the present invention
will become more apparent during the course of the follow-
ing detailed description and appended claims.
The invention may best be understood with refer-
ence to the accompanying drawings, wherein an illustrativeembodiment is shown.
In the drawings:
Figure 1 is a perspective view illustrating the
method and apparatus embodying the principles of the
present invention;
- ~6 -
3~
~igure 2 is an enlarge~ v~rtical sectlonal view
taken along the line 2-2 of Figure ~;
Figure 3 is a plan view ~ the implant part of
the apparatus;
5Figure 4 is a longitudinal section taken along
:~ the line ~-4 of ~igure 3;
Figure 5 is an end view of the implant shown in
~igure 3;
~igure 6 is an enlarged, fragmentary sectional
view illustrating the entry of the blood withdrawing can~
nula with its cooperating trocar assembled therein into
cooperating relation with the implant and specifically
the arterial passage thereof;
~igure 7 is an enlarged fragmentary sectional
view taken along the line 7-7 of Figure l;
Figure B is a top plan view of the blood with-
drawing cannula with its cooperating trocar assembled
therein;
Figure 9 is a side view of the cannula shown in
~igure 8;
Figure 10 is an end view of the cannula shown
in Figure 8; and
~ igure 11 is a perspective view of the trocar
shown in Figure 8.
- 17 -
33~
Referrin~ now more particularly to the drawings,
there is shown therein a preferred apparatus 10 ernbodying
the princi~les o~ the present invention ~or practicing the
method of the present invention. ~hile it is posslble to
utilize other apparatus in pract~cing the present method,
since the apparatus 10 is preferred the principles of the
present invention can best be understood by first consider
~ ing the pre~erred apparatus 10 ancl then considering the
- me~hod pxocedures involved ln utilizing the preferred ap-
paratus.
~; In its broadest aspects, the apparatus 10 includes
sterile tubing, generally indicated at 12, which defines an
: extracorporeal blood flow path. A pump mechanism prefer-
a~ly in the form of a peristaltic roller pumpl generally
~ 15 indicated at 14, is provided for pumping blood along the
:. extracorporeal flow path at a controlled rate from the
inlet tubing end to the outlet tubing end. In addition,
there is provided a temperature control zone preferably in
the form of a heat exchanger assembly 16 through which the
blood flowing along the extracorporeal flow pa~h has its
temperature controlled, pre~erably both by heatins and
cooling, through a control device, generally indicated at
18, ~or the liquid circuit of the heat exchanger assembly
16. Finally, the apparatus 10 includes means, generally
indicated at 20, fox communicating the inlet end of the
;~ .
. .
- 18 -
3~
tubing 12 defining the extracorporeal flow path with the
bloodstream of a patient and the outlet end of thc tubilly 12
defining the extracorporeal flow path with the bloodstream of the
patient, so that the returning blood is systemically distributed
without adversely affecting the blood depleted areas frorn which
the blood is withdrawn.
The tubing 12 may be formed of any suitable plastic
material, as, for example, vinyl polymer ~e.g. Tygon~),
polytetraflouroethylene (e.g. Teflon~), or other plastic
materials having known uses in medical applications (e.g.
Silastic~). An exemplary tubing size is 1/4" i.d., with a
convenient length being from 3 - 5'. The pump assembly 14, as
previously indicated, pre~erably embodies a peristaltic roller
type pump driven by a variable speed electric motor.
peristaltic pump is preferred because it can utilize the
replacement sterile tubing 12 for blood contact and does not
provide pump part which must be maintained in a sterile
condition. An exemplary pump is manu~actured by Sarns, having a
1-2 liter per minute capacity.
A preferred embodiment of the heat exchanger assembly 16 is
available commercially under the tradename Travenol Mini-Prime,
5MO 337, which has a 57 cc capacity and rated flow of 1-3 liters
per ~inute.
- 19 -
3~7
r~'ith reference ~o Figure 2, the ccntrol device
1~ is made up of individually known components. As shown,
there is p~ovided a cooled liquid reservoir 22 and a heated
liquid reservoir 24 each containing a bo~y of liquid. While
any liquid may be utilized a preferred e~..bodiment is water.
Each reservoir is provided with a stirring or agitating
means 26 for purposes of mixing the liquid contained
therein so as to render the temperature thereof more uniform
throughout. The cool liquid reservoir 22 is provided with
a coolinq unit, schematically indicated at 28, while the
heated liquid reservoir 24 is provided with a heating unit
30. A liquid circulating system is provided in cooperating
relation between the cooled liquid reservoir 22 and heated
. liquid reservoir 24 and the liquid side of the heat ex-
changer 16. Such circulating system includes the utili~ationof two pump assemblies, schematicaily indicated in the
drawings at 32 and 34.
As shown in ~igure 2, the pump assembly 32 is
associated with the cooling liquid reservoir 22 and includes
an inlet or suction pipe 36 extending from ~he reservoir
22 to one side of the pump 32 and an outlet pipe 38
extending therefrom. Similarly, an inl~t pipe 40 ex-
tends from the heated liquid reservoir 24 to one side of
the pump 34 which side has an outlet pipe 42 extending
therefrom. Outlet pipes 38 and 42 are interconnected by a
- 20 -
83~7
T-connector 44 which has a pipe 46 extending therefrom to
the liquid inlet side of the heat exchanger 16. A pipe 48
~xtends from the outlet of the liquid side of the heat
: e~changer 16 which by means of a Y-connection 50 coiNmuni-
ca~es with two branch conduits 52 dnd 54 extending respec-
tively to the opposi~e sides of the pumps 32 and 34. The
: circuit is completed by pipes 56 and 58 connected respec-
tively to the outlet of the opposite sides of pumps 32 and
34 and the cooled liquid reservoir 22 and heated liquid
reservoir 24 respectively. As shown, an overflow pipe 59 is
connected between the reservoirs.
The cooling unit 28 is of conventional nature and
is adapted to maintain the liquid in the reservoir 22 at a
substantially constant temperature as, for example, 30C.
Likewise, the heating unit 30 is of conventional construc-
tion and is adapted to maintain ~he liquid within the heated
liquid reservoir 24 at a substantially constant temperature
as, for example, 45C. Pump 32, when operated, serves to
meter from the reservoir 22 through pipe 36 an amount of
2~ liquid which is equal to the amount of liquid returned
through pipe 56. In a similar manner, pump 34 when operated
serves ~o meter an amount of flow from the reservoir 24
which is always equal to the amount returned through
return pipe 58. A control, schematically indicated at
60, for varying the rate of movement of the pumps 32 and
- 21 -
33~
34, e.g. electrical controls for the variable speed elec-
trical motors driving the same which form a part of the
pump assemblles schematically illustrated is operable so
that the total output of the two pumps is adjusted to and
maintained at a substankially constant rate, as for example,
approximately 10 liters per minute. The control 60 is
also operable to effect a proportional variation in the
rates which each of the two pumps assume of this total
output from 0 10 to 10-0.
Control of the pump assemblles 32 and 34 is
undertaken in accordance with the readout of three tem-
perature recording de~ices 62/ 64 and 66 placed respectively
to sense the core temperature of the patient's body (e.g. a
rectal probe or isophageal probe), the temperature ~f ~he
blood leaving the heat exchangex 16 being returned to the
patient and the temperature of the liquid enteriny the heat
exchanger, A pressure sensing device 68 is also provided in
the liquid inlet line 46. It will be understood that the
temperature sensing devices and pressure sensing devices are
of any conventional design, pre~erably of the type providing
a remote readout, as schematically indicated by corres-
ponding primed numerals.
For illustrative purposes it is suf~icient to
note that control 60 can be manually operated to determine
- 22 -
.
4~3~
the proportion of the total liquid ~low through ~he heat
exchanger which is provided by the ~ooled liquid at 30C and
the heated liquid at 45C. Control 60 thus serves to
directly vary the liquid temperature sensed by device 66
between the low limit of 30~C and upper limi' of 45~C, which
in turn will vary the temperature of the blood sensed by
: device ~4 which in ~urn will affect the patient's systemic
blood temperature and hence the temperature sensed by device
62. It will be understood that while the operation of
control 60 is set forth for illustrative purposes as being
manual, the control 60 may be rendered automatic and pro-
grammable if desired.
Referring now more particularly to Figures 3-11,
the communicating means 20 preferably comprises a totally
su~cutaneous implant device, generally indicated at 70,
which serves as the means communicating with the patient's
bloodstream and a pair of percutaneous cannula-txocar assem-
blies, generally indicated at 72 and 74, which serve as
the means for operatively communicating the implant de-
vice 70 with ~ubing 12 defining the extracorporeal flowpath. As best shown in Figures 3 7, the implant device
includes a ~ody 76 of elastomeric material such as
Silastic~, molded so as to provide an arterial passage
78, a spaced venous passage 80 and a by-pass conduit 82
connect~d between the inner end of the passage 78 and
.
: - 23 -
; .
.f~ 33~7
the inner end of the passage 80. ~s best shown in Fisure 3,
the passage, 78 and 80, together with the by-pass conduit
82, are of generally ~-shaped configurationO
Each of the passages 78 and 80 has a peripheral
cross-sectional configuration which is elongated in one
direction; namely, the direction in which they are spaced
apart, wi~h sharp points defining opposi~e ends in the
directio~ of elongation. The preferred configuration shown
is further characterized by a pair of convexly curved lines
extendinq between the sharp points, the distance between the
central portions of the convex lines being appro~imately
one-half the distance between the two end points~ While the
by-pass conduit may be of other cross-sectional configura-
tion, as shown, it too is of similar cross-sectional con-
lS fiyuration. This preferred cross-sectional configuration
for the passages 78 and 80 is provided for the purpose of
cooperatively receiving the correspondingly shaped exterior
peripheries of the cannulas of the assemblies 72 and 74,
which assemblies are so shaped for the purpose of co-
operating with a pair o~ slits 84 and 86 formed in thebody 76 in operative association with the passages 78 and
80 respectively.
As shown, each slit 84 and 86 extends from a
position exterior of the body 76 to a position of com-
munication with the innex end of the associated passage
- 24 -
~ 4~837
78 or 80. The width of each slit is generally equal to the
distance between the end points of the associated passaye
and is ori nted in its closed condition, as best shown in
Figure 4, in longitudinal alignment with a plane passing
between th~ end points of the associated passage.
In the closed condition shownl the two planar
interior surfaces of the body 76 which dcfine the respective
slit 84 or 86 are resiliently urged into engagement by the
elastomeric characteristics of the body material. ~he
engagement o the surfaces serves to exclude any spaces
which could contain fluid such as blood between the two
positions of extent of the slit as aforesaid.
The resiliency of the elastomeric material of the
body 76 also permits each slit 84 and 86 to be moved by its
lS respective cannula-trocar asscmbly 72 and 74 into an open
condition where the planar body surfaces definin~ the slit
are spread arcuately so that the profile thereof coincides
with the peripheral configuration of the associated passage
78 or 80.
To aid the entry and insertion of each cannula-
trocar assembly through its associated slit, there is molded
in embedded relation within the body 76 a pair of metallic
guide structures 88 and 90. Each ~uide structure is pre~
ferably made of a medically acceptable interior use metal,
such as stainless steel (e.g~ Vitallium Metal manufactured
by Howmedica~. The guide structures include similar
- 25 -
~ t7
inwardly tapering annular parts 92 and 94 respectively
fixed to the exterior end face of the body 76 and similar
parallel spring finger parts 96 and 98 respectivel~ em-
bedded in the exterior of the body on opposite sides of
S associated slit. The tapered part~ 92 and 94 provide the
guide assist function previously noted while the spring
finger parts 96 an~ 98 provide a spring assist function
for the slits of the elastomeric body serving ~o resiliently
urge the slit defining sur~aces toward one another i~
addition to the spring function provided by the elasto-
meric characteristics of the material of the body 76.
The implant device 70 also includes a pair o~
tubes 100 and 102 made of vascular prosthesis material.
A preferred vascular prosthesis material is woven Dacron~
marketed commercially by Meadox Medicals although any
other acceptable vascular prosthesis material may be
utilized. As best shown in Figure 1, the tube 100 has
one end thereof fixed in communicating relation with the
outer end portion of the arterial passage 78, as by being
molded in embedded relation. The opposite end of the
tube 100 is adapted to be connected, as by suture, to a
surgical openiny formed in the side wall of a femoral
artery so that the interior o~ the tube 100 is in com-
municating relation with the interior of the femoral
artery. In a like manner, one end oE the tube 102 is
- 26 -
Z3~
embedded in communicating relation wi~h the outer end por-
tion of the venous passage ~0 and its opposite end is
adapted to be sutured to a surgical side wall opening in the
associated femoral vein so that its interior is in com-
munica~ing relation with the interior of the femoral vein.
The implant device 70 also includes a layer offabric 104 which is fixed to the inner side wall of the
elastomeric body as by Silastic~ glue or the like. The
fabric 104 includes marginal portions extending laterally
outwardly from the operative inner side wall of the body 76
to which it is fixed. The fabric layer 104 and particularly
the marginal portions thereof provide for initial fixation
by suture of the body 76 during implant and for subsequent
semi-permanent ~ixation by tissue ingrowth. A preferred
fabric material is Dacron~ double velour which is marketed
commercially by Meadox ~edicals.
For identification purposes directly from the
implant device itself, radiopaque identification (not
shown) is provided on the operative outer side wall of the
elastomeric body 76. Such identification insules that the
proper cooperating cannula-trocar assemblies 72 and 74
will always be used since such assemblies can be ascer-
tained from the implant itself after total implantation
has been effected through X-ray identification.
~5 ReferrincJ now more particularly to Figures 8-11
- 27 -
3~
of the drawings, the details of con~truction of the car~nula-
trocar assemblies 72 and 74 are sho~n therein. It will be
unders~ood that since the assemblies 72 and 74 are left and
right hand mirror images of one another, a description of
one of the assemblies will suffice to give an understanding
of both. The assembly 74 is shown in assembled condition in
~igure 8 and includes a percutaneous cannula, generally
indicated at 106 and a cooperating trocar, generally indi-
cated at 108.
1~ The cannula 106 includes a tubular body which
includes a straight section 110 defining the subcutaneous
end portion of the cannula and an angular section 112
which, together with an adjacent part of the straight
section 110, defines the extracorporeal end portion of the
cannula. The cannula 106 is preferably molded o~ radiopaque
plastic material having sufficient rigidity to preven~
interior collapse when in operative pOsition within the
implant device 70. Thermoset plastics are preferred al-
though thermoplastic materials with sufficient functional
rigidity and heat stability for sterilization can be used.
An exemplary material is ethylehe-propylene-terpolymer te.g.
where the third monomer is norbornadiene) impregnated with a
radiopa~ue material such as barium sulfate.
As shown, the entire straight section 110 of the
cannula 106 has its exterior periphery for~ed with a cross-
sectional configuration which conforms with and engages
- 2~ -
33~
within the interior periphery of the body 76 defining the
artery passaye 78 or venous passage 80. Such configuxa-
tion, however, is required only in the extent o~ the sub-
cutaneous end portion which is disposed within the passage
and associated slit of the implant body during operation.
The cannula 106 includes an interior passage
114 which extends through the angular sec~ion 112 into the
straight section 110 and out of the extremity thereof.
In order to maximize the interior passage cross-sectional
area for an optimum exterior cross-sectional size, the
cross-sectional configuration of the interior passage 114
at least in the straight section 110, conforms to the
exterior cross-sectional configuration.
In this regard it will be noted that the trocar
108 consists essentially of a molded body o~ plastic ma-
terial, similar to the plastic material of the cannula
106, which provides a blade part 116 and a handle part
118. The blade part 116 is of a longitudinal extent
generally equal to the longitudinal extent of the straight
2~ section 110 of the cannula 106. T~.e main extent of the
blade part 116 has an exterio~ peripheral cross-
sectional configuration conforming wi~h the interior
cross-sectional con~iguration of the portion of the interior
passage 119 extending through the straight cannula sec-
~5 tion 110. The blade part 11~ includes a sharpened tip
- 29 ~
3~
portion 120 whic~ tapers gradually in cross-sectional con-
figuration outwardly from the aforesaid configura~ion to a
pointO
It will be noted that the extracorporeal end of
the straight section 110 of the cannula 106 is closed as by
a diaphragm or plug of elastomeric material 122 which pref-
erably is preslit (although may be imperforate) to permit
.the passage of the trocar 108, pointed end 120 first,
therethrough.
The exterior periphery of the outer end of the
angular section 112 is provided with gripping flanges.124
operakle to efect a fluid-tight connection with the in-
terior of the tubi~g 12. When the trocar lOB is withdrawn,
the elas~omeric plug slit, which has expanded to receive the
trocar, contracts to close the end of the straight section
of the cannula and insure that all of the blood will flow
outwardly through the angular section 112 and into the
tubing 12.
Formed on the exterior periphery of the straight
2~ section 110 of the cannula is an annular shoulder 126 which
forms a stop sur~ace facing in a direction ~oward the open
extremity of the straight cannula section operable to engage
the guide part 92 or 94 of the implant device when the
cannula is in its fully inserted operative position, as
shown in Figure 7. The straigh~ cannula section 110 is
- 30 -
483~
~ormed with an opening 128 which extends inwardly from
one exterior end point into communication with the interior
passage 114 at a posi~ion to register with the by-pass
conduit 82 of the implan~ body 76 when the cannula is fully
inserted, as aforesaid. Formed on the e~terior pexiphery of
the extracorporeal portion of the straight cannula section
110 is a stabilizing shield 130 which facilitates main-
tenance of the cannula on the patient when in operative
position.
A preferred procedure is to coat all of the blood
contacting surfaces o~ the cannulas 106 ~i.e. interior
passages 114) tubiny 12 and elastomeric body 76 (passages
78 and 80, conduit 82 and slits 84 and 86) with an anti~
coagulant coating. A suitable coating material for this
purpose is marketed commercially under the tradename
TDMAC~.
The manner in which the device 70 is surgically
implanted is in accordance with usual implant procedures
well ~nown to those s~illed in the art. ~or present pur-
poses suffice it to say that the elastomeric body 76 isimplanted in an arterior femoral region spaced downwardly
fxom ~he position o~ bending at the hip approximately
the distance o~ the width of a normal-sized palm ~ap-
proximately 4") as is clearly shown in ~igure 1. The
large area faces of the body 76 are preerably disposed
parallel with the skin with the face having the fabric
- 31 -
~ ~ 4~ 3~
104 ~ixed thereto in~ermost. The arterial and venous
tubes 100 and 102 extend upwardly and the free ends
are tapered and sutured to surgical openings i~ the side
walls o~ the ~emoral artery and vein respecti~ely so as
S to extend there~rom at an angle of approximately 45.
This procedure is accomplished in accordance with usual
practices relating to the use of vascular prosthesis
material.
The marginal edge portions of the fabric 104
are 5utured to tlle adjacent tissue to provide initial body
76 fixation, as aforesaid. ~11 of the exterior surfaces
of the implant device 76 are contacted with tissue includ-
ing tapered guide parts 92 and 94 (~ith fat).
AQ previously indicated, it is possible to use
known shunt devices (e.g. U.S. pa~ent No. 3,713,441) in
lieu of the device 70 so long as they provide the neces-
sary capacity which is ordinarily not the case without
modi~ication.
The advantages of the use of the implant device
2J 70 is that it is specifically intended for long-term
surgical implantation in the thig}l of cancer patients t
whereby its anastomosis to the femoral artery and vein,
creates a high~low (1-2 liters per minute) arterio-
venous conduit which may be repeatedly entered by per-
cutaneous insertion of the cannula assemblies 72 and7~. ,
- 32 -
.~ .
4~3~7
As compared with other prosthetic partially
exteriorized A-V Shunt devices as ~sed for renal hemo-
dialysis the implant device 70 red~lces ~he risk of in-
fection, reduces the risk of throm~osis, reduces the
ris~ of disruption and improves the esthetics of normal
usage. The renal dialysis experience indicates that
partially exteriorized lower extremity shunts frequently
develop infection along the tract of the shunt tubing.
The incidence and severity of this type of infection
would be increased in cancer patients by the immunosup-
pressive effects of malignancy, and the che~otherapy and
radiotherapy they frequently receive. The implantable
device '0 greatly diminishes the risk of infection and
requires no increase in the amount of surgery needed ~or
insertion. Cancer patients have a state of hypercoagul-
ability or increased tendency to form blood clots in their
normal and any arti~icial circulations. Ordinary A-V
shunts last only 2-6 months in hypocoagulable dialysis
patients, and likely will clot much sooner in those with
the "Stic~y blood" of disseminated malignancy The im-
plantable device 70 has a shorter fluid path, much o~
which will be covered by a patient's own intravascular
tissues, and hence will be less likely to thrombose.
Partially exteriorized shunts have press connections
which ~,.ay be inadvertently loosened or disconnected.
- 33 -
837
Such events have caused deaths in dialysis patients but,
in general, those shunts are small and a patient can contro.l.
a bleeding shunt before exsanguination occurs. However,
disruption of the large shunt necessary for hyperthermia
would result in massive bleeding, which could render a
patient unconscious even before the shunt could be reached
through normal clothing. This cannot happen with the de-
vice 70 as the connections are permanent, as well as
totally prvtected.
Unlike commercially known shunts, there is no
external tubing associated with the device 70. A nor~al
bath or shower could be taken by the implanted patient,
whereas those with partially exteriori~ed shunts cannot
submerge them and must resort to ~ess hyyienic methods,
lS a probable factor in their increased incidence of in-
fections. Furthermore, the device 70 does ~ot interfere
with clothing or require any sort of dressing, leaving a
patient's appearance unimpaired, an important asset to
the depressed cancer patient.
The manner in which each cannula assembly 72
or 74 i5 inserted into cooperating relation to the im-
planted device 70 should be apparent from the above. It
is of significance to note the advantages of the utili-
~ation of a main implant body 76 which provides increase~
palpation facility during cannulation. Moreover, cannu-
lation is effected in a straight line relationship
f
- 34 -
,.~
.
37
resulting in a straight line percutaneous communication
with the extracorporeal flow path. The preferred cross~
sectional con~iguration of the cannula enables simple but
effective alignment to be accomplished during insertion.
Such cross-sectional configuration ~lso provides optimal
cooperation with the slits 84 and 86 of the elastomeric
body 76 both in expandinc3 the slits during insertion and
in contracting the peripheral portion of the cannula
extending therethrough to insure a gsod fl-lid-tight con-
nection. The extension of this cannular cross-sectional
configuration with the elastomeric body passages 78 and
80 also insures non-distortion of these passages and a
full flow area o~ 4 mm or larger.
The flow capacity provided is of extreme im-
portance since it is a critical determining factor in the
time re~uired to bring the patient's blood up to the
desired treatment temperature and to the sensitivity
of the temperature control available. The approximate
1 liter minute capacity provided is based upon the aver-
2 age size of an average adult patient and, of course, shou~d
be varied to suit the particular size of the patient being
treated. The term approximately 1 liter per minute is
there~ore intended ~o comprehend within i~s meaning such
variation to suit the patient size.
It will be understood that once the inlet and
- 35 -
3'7
outlet ends of the tubing 12 are con~ected over the ~langes
124 of the .~annula of the assemblies 72 and 74 and the
associated trocars 108 of the assemblies are withdrawn,
pump 14 can be started to commence the flow of blood
along the extracorporeal flow path at the approximate
1 liter per minute as aforesaid and through the tem2erature
control zone thereof. In~tially, control 60 is set to pass
100~ 45C water through the heat exchanger 16. During
this initial trea~ment phase withdrawn blood temperatures
measured a~ 62' will show a gradual increase from the
initial normal reading of approximately 37C. The cap-
acity and effectiveness of the heat exchan~er 16 is such
that readings of the re~urning blood taken at 64 closely
approximate the 45C maximum water temperature utilized.
As the heated blood is returned to the femoral vein through
the blood receiving percutaneous cannula 106, venous
passage 80 and tube 102, it is distributed systemically
which in turn, has the effect of increasing the total
systemic tempera~ure. As the patient's core body tem-
perature increases to~ard the 91.SC level control 60 must
be operated to lower the liquid reading at 66 to a value
below 45C as, for example, 42.5C. The liquid temperature
level stabilized at 42.5C, the patient core body tempera-
ture readings at 6~, and returning blood readings will
stabilize at a desired level of approximately 41.5C and ~0.0C
respectively. This critical phase wherein the patient's
- 36 -
83}~
systemic temperature is increased and stabilized should,
as aforesaid, normally be completed within one hour, al-
though here again, variation because of patient size will
occur.
O~ce temperature stabilization is achieved as
aforesaid, treatment is continued for a time period ef-
fective ~or the particular cancer which the patient has.
A preferred minimum time for all types including simple
carcinomas is six hours although treatment times of 20
hours and longer will be re~uired for more complex ca~cer
situationsO
.. Preferably, a third phase of the present method
involves utilizing the continued blood flow through the
temperature control zone o~ the extracorporeal flow path
to reduce the blood temperature to normal and, hence, the
patient's systemic temperature to normal. This phase is
initiated by turning control 60 to pass predominately 3~C
; water through the heat exchanger 16. This has the effect of
substantially lowering the readings of the returning blood
taken at 64. ~gain, this cooler blood is distributed
systemically, causing the systemic temperature to lower
until a normal of 37C is reached. The decreasing tem-
perature phase normally will require a time period ap-
proximately the same as the initial increasing temperature
phase although usually somewhat less.
- 37 -
83~
Preferably, the patient is maintained during
treatment il a skin contacting environment approximating
that of an intensive care room. While it is within the
contemplation of the invention to provide a skin insulat-
S ing environment and even compaxable elevated temperaturesto inhaled gases, the intensive care like environment is
preferred because the temperature level o~ the skin and
respiratory system does not vary significantly from the
induced hyperthermia systemic level and access to the
patient is much more readily obtained. Moreover, the ap-
plication of radiation or chemotherapy treatments can be
carried on simultaneously if desired.
I~ thus will be seen t.hat the objects of this
invention have been fully and effectively accomplished.
It will be realized, however, that the foregoing preferred
specific embodiment has been shown and described for the
purpose of illustrating the functional and structural
principles of this invention and is subject to ch~nge
without departure from such principles. Therefore, this
inYention includes all modifications encompassed within
the spirit and scope of the following claims.
-.38 -
