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Extracorporeal Whole Body Hyperthermia
A compendium
of current
knowledge
Section
1
Section 2
Section 3
Section
4 Section
5 Section
6 Section
7
Section 1
Background and introduction
Hyperthermia has been used to treat some diseases since
ancient times. 1 , 2. However,
the field of modern hyperthermia has its roots in work and
studies that date back approximately
100 years. Research efforts have, for the most part,
been directed in the field of oncology.2 Hyperthermia's
potential in the treatment of many
other maladies has yet to be determined.
A number of methods are used to produce hyperthermia,
including microwaves, ultrasound,
paraffin wax baths, high-temperature hydrotherapy, hot water
blankets, "radiant cocoon"
devices, and extracorporeal circulation. The Food and
Drug Administration (FDA) has approved several hyperthermic
devices for treatment of various
local primary or recurrent cancers.
When body temperature changes, the metabolic rate changes as
well, at a rate of about 7 percent
per degree Centigrade (7 %/℃).
The metabolic rate increases with an
increase in body temperature (as with fever) and decreases
when body temperature decreases.
Core body temperature can be intentionally elevated using
a systemic procedure called Whole Body Hyperthermia. With the
clinical use of Whole Body
Hyperthermia, the core body temperature is elevated as high
as 42℃
(107.6℉),
either by a non-invasive or an invasive induction method.
1866 Busch
notes regression and cure of soft-tissue sarcoma and
erysipelas infection.1
1891
Dr. W.C. Coley notes
tumor stabilization or regression in malignancies after
creating an artificial fever in
patients with specific cancers.2
1927
Dr. Julius Wagner-Jauregg receives a Nobel Prize in
Medicine
and Physiology. He produced an artificial fever in patients
with neurosyphilis and found improvementin theirdisabilities.3
1920s & '30s Thermal
therapy is advocated as a treatment option for cancer5
and is also used in the treatment of
rheumatic diseases,6 asthma, and multiple
sclerosis.
Late 1930s
Studies are published on the use of a heat
device to treat patients with
syphilis and gonorrhea. Studies show significant cure rates
and no fatalities.6
Hyperthermia is used as the
standard of treatment for syphilis
when testing the efficacy of antibiotics.
1960s Dr.
Crile continues to investigate the use of hyperthermia as a
treatment for cancer.7
1970s Other
investigators independently study the use of hyperthermia for
treating specific cancers.8
1980 FDA
approves an IDE (Investigational Device Exemption) for
non-invasive Whole Body Hyperthermia in various cancers.
1984 Hyperthermia
is given legal status as an approved medical procedure8 when
local and regional hyperthermic treatments
are assigned reimbursement codes.
1984 - 94
Information on hyperthermia becomes available from a
wide variety of sources, including books, the International Journal of Hyperthermia,
and medical societies such as the American Society for
Clinical Hyperthermic Oncology, the North American
Hyperthermia Society, the European Society of Hyperthermic
Oncology, and the Asian Society of Hyperthermic Oncology. 9,10
1994
FDA gives approval for clinical studies using EWBH
to treat HIV/AIDS patients. 11,12
1997
FDA grants approval
for a cancer protocol using EWBH for investigative purposes
(IDE).
1998
grants approval to First Circle Medical for a
Phase II study using EWBH.
Table
1-1. A timeline
of modern developments in the use of hyperthermia.
Since
the FDA first began regulating medical devices in 1976, the
agency has approved many forms of
hyperthermic treatment for cancer and benign prosthetic
hypertrophy (BPH). In cancers, the type, size, vascular
structure, and physiological
position of the tumor will affect the homogeneity of the
heating.
Local hyperthermia
Local hyperthermia is the application of heat to a finite area
around a surface tumor such as lymph
node metastasis, breast tumors, or prostrate cancer. The
size of the treatment area, including depth
of penetration, can be influenced by the
method and technique used to apply heat.
Figure
1-1. An apparatus for regional hyperthermia.
Photo
from Cancer Treatment by Hyperthermfa, Radiation and Drugs,
Tadayoshi Matsuda (ed),Taylor & Francis, 1993. Used with
permission.
Regional
hyperthermia
Regional hyperthermia is used for isolated areas of the
patient's body, such as the pelvis,
stomach, or limbs. The non-homogeneous character of the
treatment egion-which may include
bones, air, and fat-can often affect the uniformity of the
heat dispersion in the treated area.
Whole
Body Hyperthermia
Whole Body Hyperthermia (WBH) employs a systemic approach
unlike the application of heat to
specific surface areas or regions of the body. With WBH,
all tissue throughout the body may be
subject to elevated temperatures. In the United
States, there are currently 11 different trials underway for
the use of Whole Body Hyperthermia.
Nine of the trials are sponsored by the National Cancer
Institute (NCI).
WBH
is accomplished through either non-invasive or invasive means.
Non-invasive WBH raises the core body temperature from a
source outside the body. The
invasive form of WBH raises the core body temperature from
inside the body to the outside by
heating the patient's blood outside the body and then returning
it to circulation.
As
previously stated, a non-invasive technique raises temperature
using an external heat source.
Non-invasive methods for elevating the core body temper-ature
eliminate the need to place a catheter within a blood vessel.
However, only a few devices are able
to achieve a core temperature of 42℃
without the risk of burns to the
patient. Non-invasive methods include:
l
Hot air, radiant devices,
"cocoons" or hyperthermic cabinets
l
Microwaves
l
Ultrasound
l
High-temperature hydrotherapy
l
Molten wax
Extracorporeal
Whole Body Hyperthermia
Extracorporeal Whole Body Hyperthermia (EWBH) is an invasive
method for achieving an elevated
core body temperature. EWBH is more "physiological"
than the use of an external heat source, in
that EWBH uses the body's cardio-vascular system to uniformly
distribute heat throughout the body. During an EWBH
procedure, a small portion of blood (5-15 percent) is
temporarily shunted outside the
patient's body, heated, and returned to the patient's
circulation, where it slowly warms
the rest of the blood in circulation. Heat transfer causes
he temperature of the tissue fed by this
heated blood to rise, resulting in an elevated
core body temperature as measured by indwelling temperature
probes.
Figure 1-2. System circuit for EWBH, as developed by
First Circle MedicalTM.
The
use of EWBH requires close monitoring of the patient to ensure
appropriate management of the
procedure. EWBH allows higher blood temperatures than
are possible with other hyperthermic induction methods. The
FDA has approved a number of
protocols for EWBH clinical trials in the fields of oncology
and virology. Further clinical research, including clinical
trials, must be conducted for
submission before EWBH receives governmental approval as a
treatment modality.
References
1.
Busch W: Verhandlungen iirztlicher Gesellschaft. Berl
Klin Wschr 3:pp. 245-246, 1866.
2.
Coley WB: The treatment of malignant tumors by repeated
inoculations of erysipelas, with a report
of 10 original cases, Am J Med Sci 105:pp. 488-511,
1891.
3.
Wagner-Jauregg J: Treatment of general paresis by
inoculation of malaria,J of Nervous and Mental Disease
55: pp. 369-375, 1922.
4.
Parks L, Smith GV: Systemic hyperthermia by
extracorporeal induction: techniques and results. In: FK
Storm, (ed) Hyperthermia in Cancer Therapy, GK Hall,
Boston, Massachusetts, pp. 401-446, 1983.
5.
Field SB, Hand JW: An Introduction to the Practical
Aspects of Clinical Hyperthermia, 1st ed, Taylor &
Francis, London, pp. 1-3, 1990.
6.
Kendall HW: Fever Therapy, Charles C. Thomas,
Springfield, Illinois, 1951.
7. Crile G: Heat as an adjunct to the treatment of cancer, Cleveland
Clinic Quarterly 28: pp. 75-89, 1961.
8.
Overgaard J: History and heritage- an introduction. In:
Overgaard, (ed) Hyperthermic Oncology, Taylor &
Francis, London, vol 2, pp. 3-8, 1984.
9.
Robins HI, Cohen JD, Neville AJ: Whole Body
Hyperthermia: Biological and Clinical Aspects. Springer-Verlag,
Berlin, 1992.
10. Yatvin M: The
rationale for hyperthermic treatment of enveloped viral
disease. Proc 7th Annual
Meeting Am Soc Clin
Hypertherm Oncol, p.25,
Decreasing the Entropy of Hyperthermia. November 1-3, Atlanta,
Georgia, 1990.
11. Steinhart CR, Ash
SR, Gingrich C, Sapir D, Keeling GN, Yatvin MB: Effect of
Whole Body Hyperthermia on AIDS
patients with Kaposi's Sarcoma: A Pilot Study. J Acq Imm
DefSyn Hum Retro 11: pp. 271-278, 1996.
12. Zablow A,
Shecterle LM, Dorian R, Kelly T, Fletcher S, Forman M, Myers
R, Holtan M,Sanfillippo L, St Cyr JA: Extracorporeal whole
body hyperthermia of HIV patients, a feasibility study, Int
J Hyperthermia 13 (6): pp. 557-586, 1997.
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