ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Bronchoscopic cryotechniques in adults

Bronchoscopic cryotechniques in adults
Literature review current through: Jan 2024.
This topic last updated: Dec 07, 2023.

INTRODUCTION — Several bronchoscopic cryosurgical techniques are available that employ extremely low temperatures to freeze tissue for destruction (cryoablation), adhesion (cryoadhesion), or biopsy (cryobiopsy) [1-3]. The most common of these is cryoablation, a procedure that is mostly used to manage inoperable airway obstruction. The equipment, principles, techniques, indications, contraindications, and complications of these modalities are reviewed here. Other bronchoscopic techniques used to manage airway obstruction are described separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults" and "Endobronchial electrocautery" and "Endobronchial photodynamic therapy in the management of airway disease in adults" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Airway stents" and "Flexible bronchoscopy balloon dilation for nonmalignant airway strictures (bronchoplasty)" and "Endobronchial brachytherapy".)

EQUIPMENT — Bronchoscopic cryotechniques require a cryosurgery device (ie, cryoprobe or cryoforceps), bronchoscope, and cooling agent (ie, cryogen). Only experts skilled in the use of this equipment should perform cryosurgery (picture 1). The procedure can be performed in the operating room or specialized procedure suites.

Cryosurgery device — Cryosurgery devices consist of a cryoprobe (ablative or adhesive procedures) or a cryoforceps (biopsy procedures), a transfer line, and a console. The cryoprobe/forceps is used to freeze the target tissue. The transfer line connects the cryoprobe/forceps to both the cooling agent storage container (eg, gas cylinder) and the console. The console controls the flow of cooling agent through the transfer line. (See 'Cryoablation' below and 'Cryoadhesion' below and 'Cryobiopsy' below.)

Cryoprobes may be rigid, semirigid, or flexible. Rigid cryoprobes have a system of reheating that induces a nearly immediate thaw phase, whereas thawing is a passive process with flexible cryoprobes, such that the freeze-thaw cycle is longer with the latter. Cryoforceps are typically flexible.

Bronchoscope — Rigid and semirigid cryoprobes can be used through a rigid bronchoscope only, whereas flexible cryoprobes and forceps can be used through either a flexible or a rigid bronchoscope. (See "Flexible bronchoscopy in adults: Overview" and "Rigid bronchoscopy: Instrumentation".)

Cooling agents (cryogen) — The cooling agents that are used most often are nitrous oxide and liquid nitrogen:

Nitrous oxide – Nitrous oxide (N2O) is the most commonly used cryogen [4]. It is stored in the liquid state at room temperature in high-pressure bottles. The vapor haze of N2O occurs at the metal tip of the cryoprobe, where it expands as it goes from high pressure to atmospheric pressure. This expansion lowers the temperature of the fluid (via the Joule-Thomson effect) and produces droplets of liquid. The result is an equilibrium temperature of -89°C in the distal two centimeters of the cryoprobe.

While carbon dioxide (CO2) has been an attractive cryogen for treating skin lesions, it was initially felt to be unsuitable for bronchoscopic cryosurgery because it produces snow when it expands at atmospheric pressure. These solid particles would obstruct the instrument channel in the bronchoscope. Technological advances, however, enable carbon dioxide systems with a cooling power similar to or equal to that of cooling temperatures provided using N2O, and given abuse/black-market value of N2O, CO2 has become the cryogen of choice in many institutions.

Liquid nitrogen – Liquid nitrogen (LN2) is stored near its saturation temperature of -196°C in vacuum-insulated containers. It evaporates as it passes through the transfer line at room temperature, leaving gaseous nitrogen to slowly cool the metal tip of the cryoprobe (the temperature of -196°C is reached in approximately one minute). Once the temperature in the transfer line becomes sufficiently low, evaporation is prevented and droplets of LN2 bombard the inner wall of the metal tip of the cryoprobe, cooling the cryoprobe at a more rapid rate [5].

Choosing among these agents is often dependent upon availability, clinician experience, and institutional biases. While research data are not available, most clinicians seem to prefer using N2O because larger freeze zones from LN2 exposes tissues to greater shear damage, and therefore possible perforation.

CRYOABLATION — Cryoablation (also known as cryotherapy) uses exceptionally low temperatures to destroy tissue with repeated cycles of rapid freezing and slow thawing of target tissue (figure 1). Cryoadhesion and cryobiopsy are defined below. Among the techniques, cryoadhesion for foreign body removal is the technique that is most commonly used. (See 'Cryoadhesion' below and 'Cryobiopsy' below.)

Basic principles and mechanisms of action — Freezing tissue to -20°C or below at a rapid rate (-100°C per minute) results in the development of intracellular ice crystals, which induce more than 90 percent cell death [6-13]. Tissue is thawed slowly to allow intracellular crystals to increase in size before they melt, resulting in further tissue destruction.

Intracellular ice crystals cause cell death by the following mechanisms:

Damaging mitochondria or other micro-organelles

Cellular dehydration

Increased concentration of intracellular electrolytes

Denaturation of membrane lipoproteins resulting in cellular swelling and increased permeability

Cryoablation also induces ischemic necrosis, independent of the direct cellular damaging effect. Vascular changes include initial vasoconstriction of arterioles and venules, altered vascular endothelium, increased permeability of vascular walls, increased blood viscosity, lower intracapillary hydrostatic pressure, decreased blood flow, and formation of platelet plugs. Ischemic necrosis from thrombosis of the target tissue microcirculation is thought to be responsible for the minimal bleeding associated with this modality. The end result is a clear line of demarcation between previously frozen tissue and unfrozen tissue.

Certain tissues are highly sensitive to freezing-induced destruction (ie, cryosensitive), while others are less sensitive (ie, cryoresistant). Examples of cryosensitive tissues include the skin, mucous membrane, granulation tissue, and tumor cells. Examples of cryoresistant tissues include fat, cartilage, fibrous, and connective tissue (ie, normal airway).

The depth of tissue penetration is approximately 3 mm, however this depends on the freeze time and cryosensitivity of the tissue [14]. This feature together with the resistance of cartilage to cryotherapy lowers the risk of airway perforation when compared with other bronchoscopic ablative techniques such as laser or electrocautery. (See "Bronchoscopic laser in the management of airway disease in adults" and "Endobronchial electrocautery".)

Importantly, the destructive effects of cryoablation are not immediate, but rather delayed such that it takes a number of days to weeks for the full effect of tissue necrosis to occur with continued tissue sloughing that often necessitates bronchoscopic removal of necrosed tissue during follow-up. Although attempts were made to overcome this delayed effect by using a larger probe to debulk tumor during the procedure, this form of cryotherapy ("cryorecanalization") was complicated by significant hemorrhage (up to 10 percent requiring argon plasma coagulation) and remains investigational [15]. (See 'Complications' below and 'Follow-up' below.)

Large amounts of endobronchial tumors may be removed by a combination of cryoadhesion and cryoablation technique. This technique can especially be helpful for endobronchial tumor debulking in patients who cannot tolerate lower FiO2 as all thermal debulking modalities (neodymium-doped yttrium aluminum garnet [Nd-YAG] laser, argon plasma coagulation [APC], electrocautery) require a fraction of inspired oxygen (FiO2) <40 percent to prevent airway fire.

Indications and efficacy — Bronchoscopic cryoablation is primarily a palliative or adjunctive therapy used for the relief of inoperable symptomatic central airway obstruction (CAO) most commonly due to malignant conditions [1-3,16]. Less commonly, it is used to treat CAO due to nonmalignant conditions, and rarely, it is used to treat hemoptysis or inoperable microinvasive lung carcinoma. Since its efficacy is dependent upon direct contact, ideal lesions are intraluminal; it is not suitable for lesions causing external compression. Since the effect of bronchoscopic cryoablation is delayed (ie, days to weeks), other modalities are generally favored for those with life-threatening obstruction who need immediate relief. Although most cases of airway obstruction are located centrally (ie, trachea and mainstem bronchi), lesions down to the second or third order of bronchi can be successfully treated with cryoablation provided they are accessible to the cryoprobe and to subsequent cleanup bronchoscopy.

The approach to and choice of modality used to treat patients with CAO as well as a comparison between the locally ablative bronchoscopic techniques are discussed separately (table 1 and table 2). Similar to other interventional techniques, cryotherapy can be used alone or in combination with stent insertion or airway dilation. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Central airway obstruction — The etiologies and efficacy to support cryoablation as a treatment for inoperable CAO due to malignant or nonmalignant obstruction are discussed in this section (table 3).

Malignant lesions — Airway malignancy is a common indication for bronchoscopic cryotherapy. Ideal patients are those who have symptomatic, intraluminal malignancies (eg, cough, dyspnea, hemoptysis, atelectasis) that are not associated with life-threatening obstruction. Numerous studies have found that cryotherapy is beneficial for airway obstruction due to malignant lesions (table 3), whether performed via rigid or flexible bronchoscopy with successful reestablishment of airway patency in up to 90 percent of patients [5,15,17-21]. Similar to other interventional techniques, cryotherapy can be used alone or in combination with stent insertion or airway dilation to maximize patency. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Data to support cryoablative therapy via rigid or flexible bronchoscopy are derived from observational case series:

Cryoablation via rigid bronchoscopy – An uncontrolled case series of 33 consecutive patients who underwent 81 cryotherapy sessions using a rigid bronchoscope found that airway obstruction was relieved in 77 percent of patients [17]. Lung function and symptoms improved in approximately 60 percent of patients. Other studies (over 800 patients in total) have reported similar results with subjective improvement in 65 to 78 percent, many of whom had more than one session of cryoablation [18,19,22].

Cryoablation via flexible bronchoscopy – A review of 225 patients found that cryotherapy delivered via a flexible bronchoscope relieved the airway obstruction in more than 90 percent of patients, although 20 percent had an additional interventional procedure (eg, argon plasma coagulation, endobronchial stent) [23]. A smaller review with 22 patients similarly found that airway obstruction was relieved in approximately 90 percent of patients, after which lung function improved in 58 percent [20].

Bronchoscopic cryoablation has been used in combination with chemotherapy and radiation with limited data to suggest that it may increase the chemo- or radiosensitivity of the tumor [13,21,22,24-26].

Cryoablation plus chemotherapy – Increased accumulation of chemotherapeutic agent within the tumor following cryotherapy has been demonstrated in small observational series [24,25]. However, the relationship between cryosurgery-induced accumulation of a chemotherapeutic agent and decreased tumor growth was reported in animal studies only [27-29].

Cryoablation plus radiation – In a review of 38 patients treated with cryotherapy followed by radiation, a higher proportion of patients achieved local control of the obstructing tumor, when compared with historical controls (65 versus 35 percent) [26]. It has been hypothesized that the possible increased sensitivity to radiation therapy may be due to cryotherapy-induced neovascularization [30].

Most cases of CAO treated with bronchoscopic cryotherapy have non-small cell lung cancer (NSCLC). However, use of this modality in patients with inoperable CAO due to other malignancies including airway carcinoid and airway metastases of extrapulmonary origin has also been reported [22,31-33]. As an example, in an uncontrolled case series, 18 patients with typical endobronchial carcinoid that was inoperable underwent bronchoscopic cryoablation [31]. Only one patient (6 percent) had a recurrence, which occurred seven years after the intervention. Similarly, in an observational series of 35 patients with mostly colorectal or renal airway metastases, endoluminal patency was increased by ≥50 percent in most patients following cryotherapy and symptoms improved in 85 percent of cases; the median survival was 34 weeks. (See "Lung neuroendocrine (carcinoid) tumors: Treatment and prognosis", section on 'Surgical resection'.)

Nonmalignant lesions — There is less evidence regarding the successful use of bronchoscopic cryotherapy for treating CAO due to inoperable nonmalignant lesions [21,34-44]. Similar to patients with malignant CAO, nonmalignant lesions suitable for cryoablation are intraluminal lesions of the trachea and mainstem bronchus that are not extensive and not associated with life-threatening obstruction. (See 'Malignant lesions' above and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Examples of nonmalignant conditions that have been successfully treated with bronchoscopic cryotherapy include the following [5,21,35-42]:

Granulation tissue due to bronchial anastomoses following lobectomy or lung transplantation

Endobronchial lipoma, hamartoma, and hemangioma

Blood clots

Mycetoma

Endobronchial tuberculosis

Removal of mucus plugs

Removal of foreign bodies

However, compared with malignant tissue which in general is more cryosensitive, some nonmalignant endobronchial lesions may be cryoresistant, such as those associated with fibrotic tissue. As an example, it is usually not used to treat fibrotic tracheal strictures as precise resection is less feasible with this technique and large circumferential zones of collateral tissue damage can occur. The latter can result in restenosis and sometimes, worsen the tracheal stricture (eg, lengthen it) which, in turn, can make definitive surgical correction more problematic. In such cases, laser, electrocautery, or argon plasma coagulation may be more appropriate. (See "Endobronchial electrocautery" and "Bronchoscopic laser in the management of airway disease in adults" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)

Hemoptysis — Bronchoscopic cryotherapy can achieve hemostasis in patients with significant hemoptysis due to visible airway lesions [17]. However, among the bronchoscopic modalities, it is generally not as effective in achieving rapid hemostasis as argon plasma coagulation (APC) or laser. In addition, delayed hemorrhage is a known complication of cryoablation that may require APC for treatment. (See "Bronchoscopic laser in the management of airway disease in adults" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)

Inoperable microinvasive carcinoma — Case reports suggest that locally ablative bronchoscopic therapies have the potential to be effective as a treatment for microinvasive radiographically occult lung cancer that is inoperable [45,46]. However, in the largest case series that demonstrated benefit, electrocautery was the most common modality used and cryotherapy was not studied [45].

Percutaneous cryoablation of parenchymal tumors under computed tomographic guidance has been described but remains investigational [47].

Contraindications

Extrinsic airway compression — Bronchoscopic cryoablation has no role when the obstruction is due to external compression since its efficacy requires direct contact with the cryoprobe. However, obstructive intraluminal components of extrinsic lesions may be subjected to cryoablation, if necessary.

Contraindications to bronchoscopy — Bronchoscopic cryoablation involves either flexible or rigid bronchoscopy, which typically requires procedural sedation or general anesthesia. Thus, contraindications to bronchoscopy, procedural sedation and/or general anesthesia are also considered contraindications to this procedure. These are reviewed separately. (See "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'General considerations and precautions' and "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications' and "Overview of anesthesia", section on 'Risk assessment'.)

Immediate relief of airway symptoms — As the full effects of bronchoscopic cryoablation take days to weeks to restore airway patency, other modalities may be preferred for patients who require immediate relief from airway obstruction or massive hemoptysis. However, it can be used to rapidly open an airway as long as the operator understands that further tissue necrosis and edema may occur over the subsequent 48 to 72 hours. Similarly, it cannot be used in patients with significant airway obstruction who are at risk of airway compromise due to airway edema, which can complicate the procedure. In these situations, a procedure that resects the tissue and immediately restores airway patency or controls bleeding (eg, electrocautery, laser, argon plasma coagulation, stenting) are more appropriate. (See "Endobronchial electrocautery" and "Bronchoscopic laser in the management of airway disease in adults" and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)

Other — Cryoablation should be avoided if mucus plugging from tissue sloughing, which is common following the procedure, is likely to worsen impending respiratory failure.

Procedure and technique — Choosing whether a flexible or rigid bronchoscope will be used typically depends upon the operator’s skill set, available equipment, and general medical and cardiopulmonary status of the patient. In general, rigid bronchoscopy is used in patients with unstable airways or with underlying cardiopulmonary disease who may not tolerate procedural sedation for flexible bronchoscopy. (See "Rigid bronchoscopy: Intubation techniques" and 'Bronchoscope' above and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Preprocedural preparation' and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Entering the tracheobronchial tree'.)

Once the endobronchial lesion has been identified bronchoscopically, the cryoprobe is inserted through the bronchoscope (either a working channel of a flexible bronchoscope or the barrel of a rigid bronchoscope):

The probe is next advanced until the tip has emerged from the distal port of the bronchoscope and is then placed adjacent to the target tissue:

The probe is passed well beyond the tip of the bronchoscope so that the growing frozen area does not come into contact with the distal extremity of the scope itself. Precise distances cannot be recommended as the angulation and appearances may change depending on the location of the lesion, the position of the bronchoscope, and the type of probe used. If during freezing, the forming ice ball is growing, the scope may need to be slightly retracted to move away from it.

For lesions that directly project into the lumen, the metallic tip of the cryoprobe is either placed onto or pushed into the target tissue. This produces circumferential freezing of maximal volume.

For infiltrating, flat lesions, the cryoprobe is placed so that it has lateral tangential contact with the target tissue.

Three freeze-thaw cycles are then carried out. Some cryoprobes are equipped with a device that measures impedance. When such cryoprobes are used, reheating is begun when a plateau between 250 and 500 kilo-ohms is reached. Subsequent freezing cycles are commenced when the impedance has fallen to 50 kilo-ohms, but before the probe becomes unstuck. If a cryoprobe is used that does not measure impedance, the freezing and reheating times must be estimated. This is done visually, by watching the halo of ice form around the cryoprobe. When the halo stops growing, freezing should be terminated and the tissue allowed to warm up. Generally speaking, a freezing time of approximately one minute is required for the first freeze-thaw cycle when liquid nitrogen is the cooling agent. The freezing time is shorter during subsequent cycles. In contrast, a freezing time of roughly 30 seconds per freeze-thaw cycle is required when nitrous oxide is the cooling agent. There is no value in prolonging the freezing beyond this time; instead, greater tissue destruction can be achieved by performing more freeze-thaw cycles.

The probe is then moved 5 to 6 mm and another three freeze-thaw cycles are performed. Each freeze zone should overlap the previous freeze zone (similar to a Venn diagram with overlapping circles). The procedure is continued until the entire endobronchial lesion has been treated. The frozen areas are larger with liquid nitrogen than nitrous oxide; thus, fewer freeze-thaw cycles are necessary and the procedure tends to be shorter when liquid nitrogen is used. (See 'Cooling agents (cryogen)' above.)

When performing cryoexcision, as with foreign body removal, the frozen tumor (or foreign body) is removed en bloc with the bronchoscope and cryoprobe during a freeze cycle. It is important to note that when performing this technique for tumor excision this is the time significant bleeding can occur and it is crucial to get the bronchoscope back in the airway as soon as possible to assess for this complication.

The cryoprobe should be removed from the flexible bronchoscope only after it has completely thawed. Any icicle adherent to the probe may damage the working channel of the bronchoscope. This is less likely to occur when using a cryoprobe placed through the barrel of a rigid bronchoscope.

It is noteworthy that any back-freezing effect (with a snow-like appearance on the outside of the probe or on the probe's tip) can be caused by contact of a cold probe with moist air (picture 2). Theoretically, this phenomenon does not correlate with the type of gas being utilized because any cold gas transported from the probe's tip back through the probe may cause a back-freezing effect. To our knowledge, there are no published reports of bronchoscopes damaged from back-freezing. Regardless, most specialists advise keeping the metal tip of the cryoprobe as well as a portion of the plastic hose of the probe fully in view beyond the tip of the flexible bronchoscope during cryo application.

As an alternative to direct contact cryoablation, a noncontact approach has been reported where liquid nitrogen is sprayed onto the lesion through a specially designed cryocatheter ("spray cryotherapy") [48-50]. It has a potential advantage of treating large areas rapidly and uniformly. Several case series report success treating nonmalignant airway strictures when combining this technique with mechanical dilation or ablative techniques [49,51]. However complications are common and include barotrauma, nitrogen gas embolism, and death. For example, in one study of 80 patients treated with spray cryotherapy, although rates of airway patency and hemostasis were high (>90 percent), 19 percent had complications including hypotension, bradycardia, tachycardia, ST segment changes, desaturation, airway perforation, and death [49]. Consequently, this approach should be considered investigational with patients only treated as part of an investigational study.

Complications — Adverse events due to bronchoscopic cryoablation occur in approximately 5 percent of cases or less, with delayed hemorrhage and airway edema being the most common.

Complications generally relate to bronchoscopy itself but can also be cryotherapy-specific [14,18,20,21]:

Bronchoscopy or sedation-related – Many of the complications associated with bronchoscopic cryosurgery are related to bronchoscopy and/or sedation. These complications are discussed separately. (See "Rigid bronchoscopy: Intubation techniques", section on 'Complications' and "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'Anticipating and mitigating Complications' and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Complications' and "Overview of anesthesia", section on 'Risk assessment'.)

Cryotherapy-related – Similar to other bronchoscopic ablative procedures, common serious complications include hemorrhage and airway wall ulceration or perforation. Unlike other ablative procedures cryotherapy is not associated with the risk of airway fire.

Hemorrhage – Specific to cryoablation, tumor necrosis and the delayed hemostatic effect can result in hemoptysis in up to 4 percent of patients, higher if cryoablative debulking/recanalization techniques are used [23]. Patients with hemorrhage should be treated similar to other patients who present with significant hemoptysis; as an example, case reports describe patients being easily treated with bronchoscopic argon plasma coagulation. (See "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Evaluation and management of life-threatening hemoptysis".)

Airway wall ulceration and perforation – This complication is less common with cryoablation than with other ablative techniques including laser and electrocautery. Any resulting pneumothorax may require a chest tube or significant airway perforation may need to be repaired. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Tracheoesophageal fistula' and "Bronchoscopic argon plasma coagulation in the management of airway disease in adults" and "Evaluation and management of life-threatening hemoptysis".)

Airway edema and mucus plugging – Mild reactive airway edema can occur that is usually not severe because the cartilaginous armature limits swelling. In addition, mucus plugging and atelectasis from cellular debris commonly occurs in the first 48 to 72 hours following the procedure necessitating repeat bronchoscopy for pulmonary toileting. In rare cases, edema and secretions may lead to airway compromise or respiratory insufficiency that sometimes requires intubation and mechanical ventilation. Therapeutic bronchoscopy is typically necessary to clean up debris, should this complication occur.

Other – Other complications including air embolism and fistula formation have not been reported but based upon other ablative procedures are theoretical possibilities. Death is rare.

While of uncertain clinical significance, an increase in circulating tumor cells has been reported with endobronchial cryotherapy [52].

Follow-up

Postoperative care — Bronchoscopic cryoablation does not require any particular immediate follow-up care in the absence of complications, other than routine post-bronchoscopy care. Patients usually can return home the same day when performed as an outpatient procedure. However, the expectoration of debris and blood is not uncommon in the days or weeks following cryoablation; atelectasis should be prevented with incentive spirometry and/or chest physical therapy. For this reason, repeat bronchoscopy is generally required. (See "Strategies to reduce postoperative pulmonary complications in adults", section on 'Lung expansion' and 'Repeat bronchoscopy' below.)

Corticosteroids are generally not needed, but they are sometimes administered for 24 hours following cryosurgery on a tracheal or subglottic lesion if the risk of airway compromise is judged to be high. Similarly antibiotics are not administered unless postobstructive pneumonia is evident.

Similar to any ablative procedure, the efficacy is generally determined by comparing the following factors before and after cryoablation: clinical status (ie, symptoms), radiologic appearance, and respiratory function. The optimal time for this evaluation is unknown but symptoms are generally assessed immediately as well as a few weeks following the procedure. In addition, because cryoablation, unlike some of the other ablative procedures (eg, laser), is invariably followed up with repeat bronchoscopy, the endoscopic appearance after the procedure can also be routinely evaluated. The general follow-up of patients with central airway obstruction is discussed separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Follow-up' and "Flexible bronchoscopy in adults: Overview" and "Flexible bronchoscopy in adults: Preparation, procedural technique, and complications", section on 'Postprocedure monitoring'.)

Repeat bronchoscopy — Repeat bronchoscopy (usually flexible bronchoscopy) is generally performed 2 to 10 days after bronchoscopic cryoablation. The repeat examination allows the extent of tissue destruction to be assessed, assure a clear and clean airway, and removal of devascularized cryoablative debris by forceps, aspiration, or cryoadhesion [18,20,21,53,54]. Additional bronchoscopic cryotherapy can be performed during the repeat examination, if necessary. (See 'Cryoadhesion' below.)

CRYOADHESION — Cryoadhesion refers to the use of a cryoprobe to freeze freely mobile endoluminal material (eg, foreign body). Material is generally frozen to temperatures of -40ºC or below. Frozen target material adheres to the probe so that it can be removed.

Foreign body removal — Cryoadhesion can be used to extract organic material including foreign bodies, mucous plugs, or blood clots (eg, due to cryoablation) [55,56]. The equipment and the procedure is similar to that described for cryoablation except the material is not subjected to thawing. (See 'Equipment' above and 'Procedure and technique' above.)

Small amounts of sterile saline can be utilized to saturate the foreign body (including nonorganic material) which further enhances freezing and consequent adhesion. The material is extracted by removing the cryoprobe through the open barrel of a rigid bronchoscope, or by removing both the cryoprobe and bronchoscope as one unit if a flexible bronchoscope is used.

Organic or biologic material is more readily frozen while inorganic matter is cryoresistant. Thus, the easiest types of objects to remove are friable items including blood clots and mucus plugs or biologic matter, such as pills, peanuts, teeth, peas, seeds, chicken bones, and chewing gum, and rarely other foreign bodies such as some types of hairpins, paper clips, and dental prostheses [57]. Though often thought that cryoadhesion cannot remove metal objects, such as most types of hairpins, nails, screws, and some tooth caps or plastic objects [58], applying sterile saline or water can allow the probe to freeze to the foreign body. The approach to patients with airway foreign bodies as well as choosing among the types of extraction tools are discussed separately. (See 'Equipment' above and "Airway foreign bodies in adults", section on 'Foreign body removal'.)

Contraindications and complications are similar to those related to bronchoscopy. In addition, there is a slight risk of accidental airway perforation, although considerably lower than that associated with cryoablation. (See "Procedural sedation in adults in the emergency department: General considerations, preparation, monitoring, and mitigating complications", section on 'General considerations and precautions' and "Flexible bronchoscopy in adults: Indications and contraindications", section on 'Contraindications' and 'Complications' above.)

CRYOBIOPSY — Use of cryobiopsy is limited to centers with expertise.

Technique – This technique involves subjecting tissue to cryofixation by a liquid cryogen to preserve tissue for subsequent morphologic and immunohistochemical analysis [59-61]. It theoretically avoids artifacts common to conventional preparation methods (eg, crush or fixation-induced artifacts) and yields biopsy samples three to four times larger than that achieved with a traditional biopsy forceps.

Cryoforceps quickly freezes the target biopsy material at the temperature of liquid nitrogen (-196ºC). Similar to cryoablation, tissue type can affect the efficacy of this biopsy modality such that lung tissue is more amenable than cartilage to cryobiopsy.

Use and efficacy – Cryobiopsy is being increasingly used during bronchoscopic resections and during bronchoscopy to biopsy endobronchial lesions. Data describing the use of cryobiopsy for parenchymal and endobronchial lesions include the following:

In the largest retrospective study to date of 1024 patients who underwent cryobiopsy for parenchymal pulmonary lesions, the overall bleeding rate was 18 percent with 3.5 percent experiencing clinically significant bleeding [62]. Pneumothorax occurred in nearly 7 percent, the majority of whom required tube thoracostomy drainage. A definitive diagnosis was achieved in over 90 percent of patients.

In one prospective series of 55 patients with endoluminal tumors, the diagnostic yield was higher with cryo-transbronchial biopsy (cryo-TBB) than with conventional TBB (89 versus 65 percent) and biopsies were larger [63]. Among patients who underwent cryo-TBB, bleeding was mild, moderate or severe in 4, 1, and 0.3 percent, respectively.

Cryobiopsy is also being increasingly used in the diagnosis of diffuse interstitial lung disease (ILD). Data supporting its use and associated complications in the diagnosis of ILD are provided separately. (See "Role of lung biopsy in the diagnosis of interstitial lung disease", section on 'Transbronchial cryobiopsy'.)

Safety – Although original observational studies suggested that the rate of complications was low (less than 5 percent), subsequent studies report higher pneumothorax and bleeding rates than standard TBB.

Newer technology may improve the safety. A new 1.1 mm cryoprobe that can be placed through a sheath is commercially available. This allows the bronchoscope to remain within the airway as the specimen is removed, potentially increasing the safety of the procedure. A small study investigating augmented-fluoroscopy-based navigation utilized this probe in 63 patients with peripheral pulmonary nodules (median nodule size 25 mm) [64]. In nine of the patients, a diagnosis was made solely by the cryoprobe, and there were no complications of major bleeding (defined as requiring intervention or admission).

SUMMARY AND RECOMMENDATIONS

Equipment – Several bronchoscopic cryosurgical techniques are available that employ extremely low temperatures to freeze tissue for destruction (cryoablation), adhesion (cryoadhesion), or biopsy (cryobiopsy). These procedures require a cryosurgery device, a bronchoscope, and a cooling agent (usually nitrous oxide). (See 'Introduction' above and 'Equipment' above.)

Cryoablation – Bronchoscopic cryoablation (also known as cryotherapy) uses exceptionally low temperatures to destroy target tissue with repeated cycles of rapid freezing and slow thawing (figure 1). (See 'Basic principles and mechanisms of action' above.)

Indications – Bronchoscopic cryoablation is primarily a palliative or adjunctive therapy used to treat patients with symptomatic central airway obstruction (CAO) due to malignant and less commonly benign intraluminal lesions that are inoperable. It can also be used to treat hemoptysis due to an endobronchial lesion and inoperable microinvasive carcinoma. It is successful in achieving airway patency and/or palliating symptoms in up to 90 percent of cases. (See 'Basic principles and mechanisms of action' above and 'Indications and efficacy' above.)

Contraindications – Bronchoscopic cryoablation should not be used in those with CAO from an extrinsic compression, those with life-threatening obstruction who need immediate relief or in those with general contraindications to bronchoscopy, general anesthesia, and/or procedural sedation. (See 'Contraindications' above.)

Procedure – Bronchoscopic cryoablation can be administered via a flexible or rigid bronchoscope. A cryoprobe (picture 1) is placed directly in contact with the target tissue. Three freeze-thaw cycles are then carried out. The probe is then moved 5 to 6 mm and another three freeze-thaw cycles are performed. This is continued until the entire endobronchial lesion has been treated. (See 'Procedure and technique' above.)

Complications – Adverse events occur in approximately 5 percent of cases or less, with delayed hemorrhage being the most common of the cryoablation-specific serious complications. Additional complications include airway perforation, airway edema, and mucus plugging, as well as complications related to bronchoscopy and/or sedation. (See 'Complications' above.)

Follow-up – Bronchoscopic cryoablation does not require any particular immediate follow-up care in the absence of complications, other than routine post-bronchoscopy care. However, repeat bronchoscopy is generally performed 2 to 10 days after the initial procedure for the removal of cryoablative debris. (See 'Follow-up' above.)

Cryoadhesion – Cryoadhesion uses a cryoprobe to freeze freely mobile endoluminal material to the probe so that it can be removed. The most common indication is the extraction of foreign bodies, mucous plugs, or blood clots. Organic material is more readily frozen whereas the extraction of inorganic objects (eg, metals, tooth caps) is less amenable to this modality. (See 'Cryoadhesion' above.)

Cryobiopsy – Cryobiopsy involves subjecting tissue to cryofixation by a liquid cryogen to preserve the tissue for subsequent morphologic and immunohistochemical analysis. Cryobiopsy is being increasingly used to obtain endobronchial and transbronchial lung tissue for solid lesions and for diffuse interstitial lung disease. (See 'Cryobiopsy' above and "Role of lung biopsy in the diagnosis of interstitial lung disease", section on 'Transbronchial cryobiopsy'.)

  1. Bolliger CT, Mathur PN, Beamis JF, et al. ERS/ATS statement on interventional pulmonology. European Respiratory Society/American Thoracic Society. Eur Respir J 2002; 19:356.
  2. Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med 2004; 169:1278.
  3. Ernst A, Silvestri GA, Johnstone D, American College of Chest Physicians. Interventional pulmonary procedures: Guidelines from the American College of Chest Physicians. Chest 2003; 123:1693.
  4. Homasson, JP, Bell, NJ. Cryotherapy in chest medicine, Springer Verlag, Paris 1992.
  5. Noppen M, Meysman M, Van Herreweghe R, et al. Bronchoscopic cryotherapy: preliminary experience. Acta Clin Belg 2001; 56:73.
  6. Gage AA, Guest K, Montes M, et al. Effect of varying freezing and thawing rates in experimental cryosurgery. Cryobiology 1985; 22:175.
  7. Smith JJ, Fraser J. An estimation of tissue damage and thermal history in the cryolesion. Cryobiology 1974; 11:139.
  8. Miller RH, Mazur P. Survival of frozen-thawed human red cells as a function of cooling and warming velocities. Cryobiology 1976; 13:404.
  9. Gage AA, Caruana JA Jr, Montes M. Critical temperature for skin necrosis in experimental cryosurgery. Cryobiology 1982; 19:273.
  10. Rand RW, Rand RP, Eggerding FA, et al. Cryolumpectomy for breast cancer: an experimental study. Cryobiology 1985; 22:307.
  11. Rubinsky, B, Ikeda, M. A cryomicroscope using directional solidification for the controlled freezing of biological tissue. Cryobiology 1985; 22:55.
  12. Gilbert JC, Onik GM, Hoddick WK, Rubinsky B. Real time ultrasonic monitoring of hepatic cryosurgery. Cryobiology 1985; 22:319.
  13. Benson JW. Combined chemotherapy and cryosurgery for oral cancer. Am J Surg 1975; 130:596.
  14. Vergnon JM, Huber RM, Moghissi K. Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic bronchoscopy of lung cancers. Eur Respir J 2006; 28:200.
  15. Hetzel M, Hetzel J, Schumann C, et al. Cryorecanalization: a new approach for the immediate management of acute airway obstruction. J Thorac Cardiovasc Surg 2004; 127:1427.
  16. Prakash UB. Advances in bronchoscopic procedures. Chest 1999; 116:1403.
  17. Walsh DA, Maiwand MO, Nath AR, et al. Bronchoscopic cryotherapy for advanced bronchial carcinoma. Thorax 1990; 45:509.
  18. Maiwand MO, Homasson JP. Cryotherapy for tracheobronchial disorders. Clin Chest Med 1995; 16:427.
  19. Rodgers BM, Moazam F, Talbert JL. Endotracheal cryotherapy in the treatment of refractory airway strictures. Ann Thorac Surg 1983; 35:52.
  20. Mathur PN, Wolf KM, Busk MF, et al. Fiberoptic bronchoscopic cryotherapy in the management of tracheobronchial obstruction. Chest 1996; 110:718.
  21. Marasso A, Gallo E, Massaglia GM, et al. Cryosurgery in bronchoscopic treatment of tracheobronchial stenosis. Indications, limits, personal experience. Chest 1993; 103:472.
  22. Asimakopoulos G, Beeson J, Evans J, Maiwand MO. Cryosurgery for malignant endobronchial tumors: analysis of outcome. Chest 2005; 127:2007.
  23. Schumann C, Hetzel M, Babiak AJ, et al. Endobronchial tumor debulking with a flexible cryoprobe for immediate treatment of malignant stenosis. J Thorac Cardiovasc Surg 2010; 139:997.
  24. Ikekawa S, Ishihara K, Tanaka S, Ikeda S. Basic studies of cryochemotherapy in a murine tumor system. Cryobiology 1985; 22:477.
  25. Homasson JP, Pecking A, Roden S, et al. Tumor fixation of bleomycin labeled with 57 cobalt before and after cryotherapy of bronchial carcinoma. Cryobiology 1992; 29:543.
  26. Vergnon JM, Schmitt T, Alamartine E, et al. Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer. Preliminary results. Chest 1992; 102:1436.
  27. Forest V, Peoc'h M, Campos L, et al. Effects of cryotherapy or chemotherapy on apoptosis in a non-small-cell lung cancer xenografted into SCID mice. Cryobiology 2005; 50:29.
  28. Forest V, Peoc'h M, Ardiet C, et al. In vivo cryochemotherapy of a human lung cancer model. Cryobiology 2005; 51:92.
  29. Forest V, Peoc'h M, Campos L, et al. Benefit of a combined treatment of cryotherapy and chemotherapy on tumour growth and late cryo-induced angiogenesis in a non-small-cell lung cancer model. Lung Cancer 2006; 54:79.
  30. Le Pivert PJ, Binder P, Ougier T. Measurement of intratissue bioelectrical low frequency impedance: a new method to predict per-operatively the destructive effect of cryosurgery. Cryobiology 1977; 14:245.
  31. Bertoletti L, Elleuch R, Kaczmarek D, et al. Bronchoscopic cryotherapy treatment of isolated endoluminal typical carcinoid tumor. Chest 2006; 130:1405.
  32. Dalar L, Ozdemir C, Abul Y, et al. Endobronchial Treatment of Carcinoid Tumors of the Lung. Thorac Cardiovasc Surg 2016; 64:166.
  33. Eaton D, Beeson J, Maiwand O, Anikin V. Endoluminal cryotherapy in the management of endobronchial metastatic tumors of extrapulmonary origin. J Bronchology Interv Pulmonol 2015; 22:135.
  34. Nassiri AH, Dutau H, Breen D, et al. A multicenter retrospective study investigating the role of interventional bronchoscopic techniques in the management of endobronchial lipomas. Respiration 2008; 75:79.
  35. Maiwand MO, Zehr KJ, Dyke CM, et al. The role of cryotherapy for airway complications after lung and heart-lung transplantation. Eur J Cardiothorac Surg 1997; 12:549.
  36. Franke KJ, Nilius G, Rühle KH. [Cryorecanalization of an endobronchial lipoma]. Pneumologie 2005; 59:685.
  37. Taviot B, Coppere B, Pacheco Y, et al. [Tracheobronchial lipomatosis. Apropos of a case]. Rev Pneumol Clin 1987; 43:42.
  38. Sim JK, Choi JH, Oh JY, et al. Two Cases of Diagnosis and Removal of Endobronchial Hamartoma by Cryotherapy via Flexible Bronchoscopy. Tuberc Respir Dis (Seoul) 2014; 76:141.
  39. Ucar N, Akpinar S, Aktas Z, et al. Resection of endobronchial hamartoma causing recurrent hemoptysis by electrocautery and cryotherapy. Hippokratia 2014; 18:355.
  40. Lee H, Leem CS, Lee JH, et al. Successful removal of endobronchial blood clots using bronchoscopic cryotherapy at bedside in the intensive care unit. Tuberc Respir Dis (Seoul) 2014; 77:193.
  41. Rojas-Tula DG, Gómez-Fernández M, García-López JJ, et al. Endobronchial cryotherapy for a mycetoma. J Bronchology Interv Pulmonol 2013; 20:330.
  42. Mu D, Nan D, Li W, et al. Efficacy and safety of bronchoscopic cryotherapy for granular endobronchial tuberculosis. Respiration 2011; 82:268.
  43. Bhora FY, Ayub A, Forleiter CM, et al. Treatment of Benign Tracheal Stenosis Using Endoluminal Spray Cryotherapy. JAMA Otolaryngol Head Neck Surg 2016; 142:1082.
  44. Samad I, Akst L, Karatayli-Özgürsoy S, et al. Evaluation of Dyspnea Outcomes After Endoscopic Airway Surgery for Laryngotracheal Stenosis. JAMA Otolaryngol Head Neck Surg 2016; 142:1075.
  45. Vonk-Noordegraaf A, Postmus PE, Sutedja TG. Bronchoscopic treatment of patients with intraluminal microinvasive radiographically occult lung cancer not eligible for surgical resection: a follow-up study. Lung Cancer 2003; 39:49.
  46. Schuurman B, Postmus PE, van Mourik JC, et al. Combined use of autofluorescence bronchoscopy and argon plasma coagulation enables less extensive resection of radiographically occult lung cancer. Respiration 2004; 71:410.
  47. Inoue M, Nakatsuka S, Jinzaki M. Cryoablation of early-stage primary lung cancer. Biomed Res Int 2014; 2014:521691.
  48. Krimsky WS, Broussard JN, Sarkar SA, Harley DP. Bronchoscopic spray cryotherapy: assessment of safety and depth of airway injury. J Thorac Cardiovasc Surg 2010; 139:781.
  49. Finley DJ, Dycoco J, Sarkar S, et al. Airway spray cryotherapy: initial outcomes from a multiinstitutional registry. Ann Thorac Surg 2012; 94:199.
  50. Browning R, Parrish S, Sarkar S, Turner JF Jr. First report of a novel liquid nitrogen adjustable flow spray cryotherapy (SCT) device in the bronchoscopic treatment of disease of the central tracheo-bronchial airways. J Thorac Dis 2013; 5:E103.
  51. Janke KJ, Abbas AE, Ambur V, Yu D. The Application of Liquid Nitrogen Spray Cryotherapy in Treatment of Bronchial Stenosis. Innovations (Phila) 2016; 11:349.
  52. Chudasama D, Rice A, Soppa G, Anikin V. Circulating tumour cells in patients with lung cancer undergoing endobronchial cryotherapy. Cryobiology 2015; 71:161.
  53. Homasson, JP. Bronchoscopic cryotherapy. J Bronchol 1995; 2:145.
  54. Homasson JP, Thiery JP, Angebault M, et al. The operation and efficacy of cryosurgical, nitrous oxide-driven cryoprobe. I. Cryoprobe physical characteristics: their effects on cell cryodestruction. Cryobiology 1994; 31:290.
  55. Rafanan AL, Mehta AC. Adult airway foreign body removal. What's new? Clin Chest Med 2001; 22:319.
  56. Weerdt S, Noppen M, Remels L, et al. Successful removal of a massive endobronchial clot by means of cryotherapy. Journal of Bronchology 2005; 12:23.
  57. Jabbardarjani R, Kiani A, Arab A. Nat Res Inst Tuberc and Lung Dis 2009; 8:60.
  58. Hewlett JC, Rickman OB, Lentz RJ, et al. Foreign body aspiration in adult airways: therapeutic approach. J Thorac Dis 2017; 9:3398.
  59. Babiak A, Hetzel J, Krishna G, et al. Transbronchial cryobiopsy: a new tool for lung biopsies. Respiration 2009; 78:203.
  60. Hetzel J, Hetzel M, Hasel C, et al. Old meets modern: the use of traditional cryoprobes in the age of molecular biology. Respiration 2008; 76:193.
  61. Franke KJ, Szyrach M, Nilius G, et al. Experimental study on biopsy sampling using new flexible cryoprobes: influence of activation time, probe size, tissue consistency, and contact pressure of the probe on the size of the biopsy specimen. Lung 2009; 187:253.
  62. Herth FJ, Mayer M, Thiboutot J, et al. Safety and Performance of Transbronchial Cryobiopsy for Parenchymal Lung Lesions. Chest 2021; 160:1512.
  63. Schumann C, Hetzel J, Babiak AJ, et al. Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions. J Thorac Cardiovasc Surg 2010; 140:417.
  64. Pertzov B, Gershman E, Izhakian S, et al. The LungVision navigational platform for peripheral lung nodule biopsy and the added value of cryobiopsy. Thorac Cancer 2021; 12:2007.
Topic 4407 Version 38.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟