Pulmonary Medicine

Interventional Bronchoscopy: Cryotherapy

General description of procedure, equipment, technique

Cryotherapy

Initially defined in 1995 and subsequently described in European Respiratory Society (ERS) and American Thoracic Society (ATS) guidelines, interventional pulmonology is "the art and science of medicine as related to the performance of diagnostic and invasive therapeutic procedures that require additional training and expertise beyond that required in a standard pulmonary medicine training program." Clinical entities encompassed within the discipline include complex airway management, benign and malignant central airway obstruction, pleural diseases, and pulmonary vascular procedures.

Diagnostic and therapeutic procedures pertaining to these areas include rigid bronchoscopy, transbronchial needle aspiration, autofluorescence bronchoscopy, endobronchial ultrasound, transthoracic needle aspiration and biopsy, laser bronchoscopy, endobronchial electrosurgery, argon-plasma coagulation, cryotherapy, airway stent insertion, balloon bronchoplasty and dilatation techniques, endobronchial radiation (brachytherapy), photodynamic therapy, percutaneous dilatational tracheotomy, transtracheal oxygen catheter insertion, medical thoracoscopy, and image-guided thoracic interventions. This presentation focuses on cryotherapy.

Cryotherapy deals with the destruction of biological materials through the cytotoxic effects of freezing. Documents from 3500 BC described the use of cold as treatment for swelling and war wounds, and Hippocrates noted the use of cold to treat orthopedic injuries. The Joule-Thomson effect, which describes the cooling of a gas or liquid when forced through a valve from a high-pressure to a low-pressure region, is the basis for cryoprobe therapy.

Damage induced by freezing occurs at several levels, including the molecular, cellular, and structural levels, as well as at the level of whole tissues. The effect of freeze injury is influenced by many factors, and survival of cells is dependent on the cooling rate, the thawing rate, the lowest temperature achieved, and whether repeated freezing-thawing cycles occur. Certain tissues (e.g., skin, mucous membranes, and granulation tissue) are cryosensitive, while others (e.g., fat, cartilage, and fibrous or connective tissue) are cryoresistant. Tissue cryosensitivity depends on cellular water content, so tumor cells may be more sensitive than normal cells.

Several cooling agents may serve as cryogens. These agents are generally used in the liquid phase so, upon vaporization, they remove heat at a constant temperature (heat of vaporization). Several studies have shown that the core temperature needed for lesion destruction is between -20°C and -40°C. Freezing to -40°C or below at the rapid rate of -100°C per minute will cause more than 90 percent of cells to die.

Nitrous oxides (e.g., N2O) are the most common cooling agents used. The vapor haze of N2O occurs at the metal tip of the cryoprobe, where it expands from a high pressure to atmospheric pressure (the Joule-Thomson effect). This expansion lowers the temperature of the fluid, producing droplets of liquid and reaching equilibrium at - 89°C at atmospheric pressure.

Cryoprobe devices can be rigid, semi-rigid, or flexible. Rigid and semi-rigid cryoprobes can be used only with a rigid bronchoscope, while flexible cryoprobes can be passed through the channel of a fiberoptic bronchoscope. The diameter of a flexible probe requires a larger working channel than that of a fiberoptic bronchoscope (2.6-3.2 mm).

Monitoring of tissue freezing remains a problem. The empirical method relies on the experience of the operator, who relies on the change in color or consistency of the frozen tissue and the length of freezing procedure. In clinical studies that use rigid, semi-rigid, or flexible cryoprobes, each freeze-thaw cycle is about 30 seconds. The thaw phase is almost immediate when using rigid probes that have a system of reheating; however, when flexible probes are used, thawing is achieved by equilibration with body temperature, thus increasing freeze-thaw cycle times.

Indications and patient selection

Cryotherapy is indicated for tracheobronchial obstruction. Patient selection criteria are similar to those used for laser therapy, APC, or electrocautery, except when there is an urgency to treat. In addition, cryotherapy may be used for extraction of foreign bodies, blood clots, and mucus plugs.

Contraindications

The absence of an endobronchila lesion is a contraindication.

Details of how the procedure is performed

The flexible cryoprobe is passed through the working channel of the bronchoscope, the tip of which is placed in the proximity of the tumor. Activation of the cryoprobe using a foot pedal elicits ice ball formation on the tip of the probe within thirty seconds. Two to three freeze-thaw cycles, each lasting one minute, are applied to the same or adjacent area. The tissues are frozen at -30° to -40°C.

The tip of the probe may be applied perpendicularly or tangentially, or it may be driven into the tumor mass. The metallic tip of the cryoprobe is placed on the tumor or pushed into it so that it produces circumferential freezing of maximal volume. Two to three freeze-thaw cycles are carried out at each site. The probe is then moved 5-6 mm, and another three cycles of cryotherapy are carried out in the new area. The hemostatic effect of freezing is often sufficient to stop hemoptysis when it is present at patient presentation.

Interpretation of results

Not applicable

Performance characteristics of the procedure (applies only to diagnostic procedures)

Not applicable.

Outcomes (applies only to therapeutic procedures)

In a report describing eighty-one cryotherapy sessions performed in thirty-three consecutive patients with dyspnea, hemoptysis, cough, or stridor, most experienced improvement in symptoms. Another report of six hundred patients treated with cryotherapy found that 78 percent noticed a subjective improvement in symptoms, with reduction in cough (64%), dyspnea (66%), hemoptysis (65%), or stridor (70%).

Other studies have described cessation of hemoptysis in 80 percent of treated patients and reduction in dyspnea in 50 percent. Similar findings in a smaller series using fiberoptic bronchoscopy or by improvement of pulmonary function was seen in 58 percent of patients, and these changes in lung function correlated with symptoms

Cryotherapy has been shown to be useful in recanalization of airways with endobronchial tumors, and success rates as high as 91 percent have been reported. Cryotherapy has also been helpful in procuring larger transbronchial biopsy specimens.

Recently, there has been renewed interest in cryotherapy for treatment of early stages of airway cancer. In one study of thirty-six patients with a total of forty-four lesions ("in situ" or microinvasive tumors of the upper airways or bronchial tree), complete clinical and histological control of the tumor was achieved in 88.8 percent with a mean follow-up of thirty-two months. The mean survival of this population was thirty months.

Benign lesions have been treated with cryotherapy with good results, particularly for granulomatous tissue, which is highly sensitive to the effects of cold. Cryotherapy may yield good results in management of carcinoids, cylindromas, and laryngotracheal papillomas when resectional surgery is not an option.

Cryotherapy has been used with success in the extraction of foreign bodies, mostly in the removal of friable biological matter, such as pills, peanuts, teeth, and chicken bones. The technique has also proved helpful in the removal blood clots, mucus plugs, and tissue slough.

Alternative and/or additional procedures to consider

Alternatives to cryotherapy include ND:YAG laser, APC, and electrocautery.

Complications and their management

Bleeding, when it occurs, must be tamponaded.

What’s the evidence?

Breasted, JH. "The Edwin Smith surgical papyrus". University of Chicago Oriental Institute. 1930.

Early description of the use of cold therapy.

Carpenter, RJ, Neel, HB, Sanderson, DR. "Cryosurgery of bronchopulmonary structures. An approach to lesions inaccessible to the rigid bronchoscope". Chest. vol. 72. 1997. pp. 279.

One of the first papers to describe the use of cryotherapy in the lung.

Deygas, N, Froudarakis, ME, Ozenne, G, Jouve, S, Fournel, P, Vergnon, JM. "Cryotherapy in early superficial bronchogenic carcinoma". Eur Respir J. vol. 12. 1998. pp. 266 S.

A description of the use of cryotherapy for treatment of carcinoma in situ.

Hetzel, M, Hetzel, J, Schumann, C, Marx, N, Babiak, A. "Cryorecanalization: a new approach for the immediate management of acute airway obstruction". J Thorac Cardiovasc Surg. vol. 127. 2004. pp. 1427-31.

Report on the use of cryotherapy in management of acute airway obstruction, a possibly dangerous technique.

Homasson, JP. "Cryotherapy in pulmonology today and tomorrow". Eur Resp J. vol. 2. 1989. pp. 799-801.

A review of cryotherapy.

Homasson, JP, Renault, P, Angebault, M, Bonniot, JP, Bell, NJ. "Bronchoscopic cryotherapy for airway strictures caused by tumors". Chest. vol. 90. 1986. pp. 159-164.

Early paper discussing the resurgence of cryotherapy as a useful technique.

Maiwand, MO. "Cryotherapy for advanced carcinoma of the trachea and bronchi". Br Med J. vol. 293. 1986. pp. 181-182.

A large series focused on palliation of lung cancer.

Maiwand, MO, Homasson, JP, Mathur, PN, Beamis, JF. "Cryotherapy for tracheobronchial disorders". Clinics in chest medicine. W.B. Saunders Company. 1995. pp. 427-443.

A comprehensive review of cryotherapy.

Mathur, PN, Wolf, KM, Busk, MF, Briete, WM, Datzman, M. "Fiberoptic bronchoscopic cryotherapy in the management of tracheobronchial obstruction". Chest. vol. 110. 1996. pp. 718-23.

First report in the United States on the use of flexible bronchoscopy with a cryoprobe.

Neel, HB, Farrell, KH, Payne, WS, De Santo, LW, Sanderson, DR. "Cryosurgery of respiratory structures 1. Cryonecrosis of trachea and bronchus". Laryngoscope. vol. 83. 1973. pp. 1062.

A description of the effects of cryotherapy on tissue.

Sheski, FD, Mathur, PN. "Endobronchial cryotherapy for benign tracheobronchial lesions". Chest. vol. 114. 1998. pp. 261-262s.

A review of the use of cryotherapy in the treatment of benign lesions.

Vergnon, JM, Schmitt, T, Alamartine, E, Barthelemy, JC, Fournel, P, Emonot, A. "Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer". Chest. vol. 102. 1992. pp. 1436-40.

A large series report on use of cryotherapy in lung cancer palliation.
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