Cryotherapy in pulmonology today and tomorrow J. P.

Eur Respir J
1989, 2,
EDITORIAL
79~801
Cryotherapy in pulmonology today and tomorrow
J. P. Homasson*
The analgesic and anti-inflammatory properties of ice
have been known for several centuries. But it was as
recent as 1961, that CooPER and LEE [1] reported a
cryothalamectomy, and introduced the closed tip
cryoprobe, using liquid nitrogen as a coolant source, thus
allowing local application of freezing for the treatment
of cancer in many different areas. Many medical
specialities use cryosurgery, but the treatment of airway
strictures and malignant tumours of the tracheobronchial
tree is a new application of this technique [2- 7], made
possible by the miniaturization of the probes.
The technique utilizes a nitrous oxide cryoprobe, which
employs the Joule-Thomson effect (cooling of a gas upon
sudden expansion from a high to a low pressure region).
The entire probe is isolated, except the distal tip. The
temperature obtained at the tip of the cryoprobe is -so·c
but the tissues are frozen at ~o·c. With the French
probes, a combined impedance meter measures variations
of resistance of tissues during the process of freezing and
thawing [8].
The cryolesion is well known; two factors contribute
to the tissue destruction, namely physical and vascular.
The physical effect is predominant, with cellular dehydration and intracellular cystallisation contributing to cell
death [9, 10]. MAzUR [11, 12] has suggested that the
presence of intracellular ice and its crystallisation has a
destructive effect on intracellular membranes. An electron microscopic study of bronchial, lung and pleural
tissues recently confirmed this [13]. Complex biochemical effects secondary to cellular dehydration and an
increase in intracellular electrolyte concentration contribute to the denaturation of lipoproteins in cell membranes.
A cryothrombosis due to several factors completes the
destruction: vaso-constriction, modification of the vascular epithelium, increase in permeability of the vascular
walls and increase in blood viscosity.
Nevertheless, histopathological findings are not modified by freezing when biopsies are made immediately
after cryotherapy. The secondary cellular changes in the
days following cryotherapy result in a cellular necrosis:
bronchial biopsy usually shows a necrotic eosinophilic
substance: tumour tissue is no longer visible and
therefore entirely destroyed [5].
Experimental studies (14, 15] showed that following
application of temperatures of -8o·c for 60 s to the
tracheal epithelium of animals, a superficial ulcer formed
*Cenlre Hopi!alicr Specialise en Pncumologic, 24 rue Albcrt Thurcl,
94669 Chevilly- Laruc Ccdcx, France.
within 48 h, which was completely re-epithelialized
within four days. The initial regenerated epithelium is a
simple columnar layer, but within six weeks it differentiates to a more normal appearing tracheal epithelium.
Some authors consider [16-18) that cryosurgery may
induce an immunological effect it is still only a
hypothesis and no definite conclusion has yet been
possible.
The major indication of bronchoscopic cryotherapy is
tumour destruction. For malignant tumours, cryotherapy
does serve as a good alternative for palliative tumour
control. It is an efficient method for destroying benign
tumours, and the destruction of tracheal granulomatous
tissues appears to be simple and offers a complete cure.
Indications appear to be the same as laser therapy;
nevertheless, the result is delayed, and the technique is
not useful for acute respiratory distress. However, it is
cheap and easier to use than laser therapy, and tumour
lesions seem to grow slower than after laser therapy [7].
Other applications have been described: trcalment of in
situ carcinoma, and of tracheal or bronchial stenosis [19].
Pleural and lung cryobiopsies during thoracoscopy are
a new application of the technique [20] . The cryoprobe
is passed via a trocar and applied to the area of pleura
(partietal or visceral) to be biopsied under direct vision.
During the parietal cryobiopsy the patients do not
complain of any pain, which reinforces the well known
analgesic effect of freezing. The risk of haemorrhage or
pneumothorax is reduced. The microscopic findings are
not modified by freezing and the quality of biopsy
specimen is equivalent to surgical biopsy.
Cryoanalgesia appears to offer a practical technique
for controlling pain after thoracotomy. Freezing
intercostal nerves at the end of the operation gives a
reversible nerve block with no undesirable sequelae
[21-23). After thoracotomy, cryoanalgesia has an
important role in the prevention of pulmonary complications, allowing early mobilisation with physiotherapy. It
appears to be a simple method, and offers advantages not
achieved by any other available technique.
Another use of freezing has been described in China,
namely local excision of tumours at thoracotomy [24,
25). This technique is indicated for patients with poor
pulmonary or cardiac function, when lobectomy or
radiotherapy are excluded, for lung metastasis and when
the tumour found during thoracotomy is too extensive
for resection. The tumour is held by a special ring forceps;
a plastic cylinder of corresponding size is placed against
the tumour surface within the ring forceps and liquid
nitrogen is Lhen poured into the cylinder. A large frozen
800
J.P. HOMASSON
portion of tumour is then easily enucleated, the residual
tumour is also frozen but left in place.
Interesting advances are being made both with development of the apparatus, and with the application of
cryotherapy. The cryoprobes are now safe, efficient and
robust. lL is still necessary to use a rigid bronchoscope,
and bronchial lesions of upper lobes are often inaccessible. Thus it is advantageous to use flexible probes.
German and French ones will be commercially available
in a few months. Prototypes have been used for the past
two years [26, 27], and can be passed through fiberoplic
bronchoscopes. A modified impedance meter connected
to a processor, will probably facilitate manipulation of
the apparatus. Cryotherapy is now well known in France:
at the end of 1988, a study group was formed and research
is currently in progress. Immunological studies are being
carried out by VERGNON (personal communication),
whereby bronchial tumours are transplanted on to "nude"
mice and cryotherapied. Veterinary surgeons have being
working on the same subject [28]. It seems that radiotherapy and chemotherapy may be more effective after
cryotherapy, and a multicentre study is in progress to
evaluate the association of cryo-radiotherapy in France.
Antimitotic drugs would appear to concentrate in the
tumour site immediately after cryotherapy [29, 30]; this
is being tested in an isotope study using bleomycin marked
with 57 Co, in a small group of patients [31]. Electron
micrographs may aid the understanding of cryodestruction of bronchial tumours.
Other research in cryotherapy is being carried out in
other countries but in different specialities (e.g. phlebology, dermatology, heart surgery, urology) and more
cross-fertilisation is needed between specialities. At
present there is very liulc being wriLten about this technique in the chest literature and the most recent studies
have all come from Europe [4, 5, 7, 27, 32].
Acknowledgement: I would like to express
my thanks to N.J. Bell (M.D. Oxford, England)
for reviewing the text.
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PULMONARY CRYOTHERAPY
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