ENDOBRONCHIAL ABLATIVE THERAPIES. Christopher Cortes, MD, FPCCP

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ENDOBRONCHIAL ABLATIVE THERAPIES Christopher Cortes, MD, FPCCP

Choice of Ablative Therapy Size of the lesion Location of the lesion Characteristics of the lesion Availability of the different therapies Training & skills of the bronchoscopist Bolliger CT et. al. ERS/ATS Statement on Interventional Pulmonology. Eur Respir J. 2002; 19:356-73.

Indications Lesion occupying >50% of the airway with symptoms of dyspnea Hemoptysis Recurrent pneumonia Intractable cough Bolliger CT et. al., Eur Respir J. 2002 Amjadi K et. al., Respiration. 2008 Folch E et. al., Semin Respir Crit Care Med. 2008 Bolliger CT et. al., Eur Respir J. 2006

CONTRAINDICATIONS ABSOLUTE Extrinsic compression of airway RELATIVE Inability to lower FiO2 to 40% Distal airway obstructions Airway obstruction present for > 4 weeks Length of obstruction > 4 cm Bolliger CT et. al., Eur Respir J. 2006 Klopp AH et. al., Clin Lung Cancer. 2006 Ung YC et. al., Brachytherapy. 2006

COMPARISON OF ENDOBRONCHIAL ABLATIVE THERAPIES LASER ELECTROCAUTERY ARGON PLASMA COAGULATION CRYOTHERAPY BRACHYTHERAPY PHOTODYNAMIC Time to improvement Immediate Immediate Immediate to days Days to weeks Days to weeks Days to weeks Control of bleeding Excellent Excellent Excellent None None None Tumor specific No No No No Yes Yes Depth of penetration Variable, dependent on power settings Variable, dependent on power settings 3mm Variable, dependent on radiation dose 3mm 3mm Expense +++ + ++ ++ ++++ ++++

LASER Uses light energy transmitted through fibers to desiccate endoluminal tissue Types: potassium titanyl phosphate, yttrium aluminum pevroskite, carbon dioxide and Nd:YAG Predictable tissue effects, precise area of treatment effect, rapid and immediate results, repeatability of treatments, and ability to blend with other airway interventions

LASER Power Settings Low-power: shallow effect and coagulate tissue High-power: penetrate deeper and result in carbonization and vaporization of tissue Distance from the tip of the laser fiber 1cm away from the lesion: shallow penetration 3mm-4mm away from the lesion: deeper penetration

LASER Effects are immediate ~ dramatic improvement in patient s complaints and symptoms Surrounding tissue is also affected ~ thermal injury & cell death Delayed effects seen in 48 to 96 hours Results in further improvement in airway lumen size

LASER

ELECTROCAUTERY Uses the flow of electricity to generate heat Effects depend on several variables: nature of the lesion, current waveform properties, and the power setting, machine mode, and the type of probe used Electrical current waveforms High frequency: cut mode Low frequency: coagulation mode

ELECTROCAUTERY Power Settings Low-power: shallow effect and coagulate tissue High-power: penetrate deeper and result in carbonization and vaporization of tissue Immediate ablative effect Delayed effect ~ cytocidal effect of heat generation Cost is minimal Common instruments: a probe, snare, knife, and forceps

ELECTROCAUTERY

ARGON PLASMA COAGULATION Uses argon gas as the media through which the electrical current flows to the tissue It has superficial effects on tissues and is an excellent option for coagulation Shallow effects ~ not optimal for debulking Immediate tissue ablative effect as well as delayed cytocidal effect of heat transmission

CRYOTHERAPY Uses extreme cold to treat airway lesions Special probe - rapidly expanding gas (e.g. nitrous oxide, liquid nitrogen) flows to the tip of the catheter and cools it to -40 o C Active cooling (30-60 seconds) followed by period of passive rewarming Freeze-and-thaw cycle is repeated 2 to 3 times for maximal effect

CRYOTHERAPY ISSUES: Lacks precision, shallow effect and has no immediate effect Maximal tissue destruction occurs 1 to 2 weeks after and requires repeated treatment Time consuming

BRACHYTHERAPY Use of radiation to treat malignant lesions Specialized catheter placed under direct visualization or with assistance of fluoroscopy or ultrasound Radiation seed are advanced through the catheter and into the desired location Not used for lesions that are associated with acute complaints of dyspnea

BRACHYTHERAPY Used for long lesions growing into the airways or compressing the airways Offered to patients who have already received maximal external beam radiation and who are not candidates for more conventional ablative techniques No immediate effect Maximal effect ~ several weeks after Expensive and requires specialized facilities

PHOTODYNAMIC THERAPY Application of light energy to tissues that have been penetrated with photosensitizer Photosensitization agent (Photofrin) ~ administered through IV injection 2-3 days before active metabolizing cells and malignant cells

PHOTODYNAMIC THERAPY Light probe emits specific frequency and activates photosensitizing agent Generation of reactive oxygen species damage cellular structures and leads to cell death Repeated as necessary to reach deeper tissue Does not result in immediate effect Maximal effect ~ several days after

COMPLICATIONS Type of Therapy Airway Perforation Hemorrhage Airway Fire Air Embolism Respiratory Failure MI, Arrythmia Death Laser Possible Possible Possible Very rare Possible Rare Very rare Electrocautery Possible Possible Possible No Possible Rare Very rare APC Unlikely Unlikely Possible No Possible Rare Very Rare Cryotherapy No No No No Possible Rare Very rare PDT No No No No Possible Rare Very rare Brachytherapy No Unlikely No No Possible Rare Very are Rate of complication vary significantly among pulmonologist, airway centres, and patients. difficult to site as such qualitative estimates are commonly described. Precise estimates of risk are

COMPLICATIONS Rare complications (respiratory failure, MI, cardiac arrhythmia and death) - more frequent Prolonged sedation Need for decreased FiO2 which may allow transient or prolonged hypoxemia Airway perforation ~ pneumomediastinum, pneumothorax and hemorrhage Deploy therapy parallel to the airway Frequently re-evaluate tissue planes dissected

COMPLICATIONS Bleeding/hemoptysis Laser and electrocautery - massive PDT and brachtherapy - delayed (mucosal tissue breakdown and ulceration) Airway fires Keep oxygen concentration below 40% or preferably below 30% Keep tip of the laser fiber or electrocautery at least 1 cm away from the end of the bronchoscope Consider using LMA or rigid bronchoscope

COMPLICATIONS Air embolism - cerebral infarction Rare complication of laser therapy Result of bronchial wall blood vessel disruption in the setting of positive pressure ventilation and the use of gas cooled laser fiber Limited by using noncontact laser fiber and non-gas-cooled fibers

PRACTICAL CONSIDERATIONS Hot therapies (laser, electrocautery, and APC) FiO2 must stay below 40% to reduce the risk of airway fires When advanced airways are needed, a LMA instead of an endotracheal tube should be considered to reduce the risk for airway fires Using a rigid bronchoscope should be considered, when available and appropriate to the situation, to reduce the risk for airway fires Ideal interventions often are associated with immediate clinical improvement

PRACTICAL CONSIDERATIONS Electrocautery and APC Due to the electrical current, caution should be used in patients with pacemakers Wide array of specialized instruments that allow for unique interventions (for electrocautery) Electrocautery achieves similar results to laser ans is more economical Cryotherapy Results are delayed It is able to be performed with any inspire level of oxygen It is tim consuming

PRACTICAL CONSIDERATIONS Photodynamic therapy Associated with intense photosensitivity to sunlight Results may take days to weeks Repeat bronchoscopy is required to remove sloughed tissue Applicable only in patients with tumors that have significant blood flow Brachytherapy Additional radiation may be delivered to areas that have received maximal external beam radiation It can be delivered to long lesions or lesions that are external to and compressing the airway It is expensive and requires special facilities

REFERENCES Bolliger CT et. al., ERS/ATS statement on interventional pulmonology. Eur Respir J 2002; 19:356-73. Amjadi K et. al., Impact of interventional bronchoscopy on quality of life in malignant airway obstruction. Respiration 2008; 76:421-8. Litle VR et. al., Photodynamic therapy for endobronchial metastases from nonbronchogenic primaries. Ann Thorac Surg 2003; 76:370-5. Hujala K et. al., Endotracheal and bronchial laser surgery in the treatment of malignant and benign lower airway obstructions. Eur Arch Otorhinolaryngol 2003; 260:219-22. Cheila A et. al., Combined Nd-YAG laser/hdr brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study. Lung Cancer 2000; 27:169-75. Folch E and AC Mehta. Airway interventions in the tracheobronchial tree. Semin Respir Crit Care Med 2008; 29-441- 52 Bolliger CT et. al., Therapeutic bronchoscopy with immediate effect: laser, electrocautery, argon plasma coagulation and stents. Eur Respir J 2006; 27:1258-71. Klopp AH et. al., Endobronchial brachytherapy: an effective option for palliation of malignant bronchial obstruction. Clin Lung Cancer 2006; 8:203-7. Ung YC et. al., The role of high-rise-rate brachytherapy in the palliation of symptoms in patients with non-small cell lung cancer: a systematic review. Brachytherapy 2006; 5:189-202. Tremblay A and CH Marquette. Endobronchial electrocautery and argon plasma coagulation: a practical approach. Can REspir J 2004; 11:305-10. Vergnon JM et. al., Place of cryotherapy, brachytherapy, and photodynamic therapy in therapeutic bronchoscopy of lung cancers. Eur Respir J 2006; 28:200-18. Ross DJ et. al., Pathogenesis of systemic air embolism during Nd-YAG laser photo resection. Chest 1998; 94:660-2

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