Tracheobronchial Stenosis · Tracheobronchial stenosis Systemic therapy Bronchoscopy Bioabsorbable...

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Tracheobronchial Stenosis Causes and Advances in Management Jonathan Puchalski, MD, MEd a, *, Ali I. Musani, MD b INTRODUCTION Airway stenosis may involve the glottis, subglottis (below the vocal cords but above the inferior cricoid), or tracheobronchial tree. It may be con- genital or acquired, caused by benign or malignant diseases, focal or diffuse, and present with various symptoms. Patients with significant stenosis may present with dyspnea, wheezing, or stridor. Stridor occurs when the airway diameter in an adult dimin- ishes to approximately 6 mm. Given that congenital and pediatric stenosis may often have different causes and require different treatments, this article focuses primarily on adult stenosis of the tracheo- bronchial tree. EVALUATION Beyond the physical examination, evaluation often includes a combination of physiologic, radio- graphic, and endoscopic assessments. Pulmonary function tests may show a delay in reaching peak expiratory flow, a truncation of peak expiratory and peak inspiratory flow, and/or an abrupt decrease in expiratory flow at the end of expiration. There may be flattening of the inspiratory and expiratory phases in the presence of fixed upper airway obstruction. A chest radiograph may detect tracheal disease although multiplanar computed tomography (CT) is useful for characterization of disease extent, exact configuration, and for plan- ning treatment. This airway CT is different from neck or chest CT scans with thinner cuts that allow for three-dimensional reconstruction. Often called virtual bronchoscopy, the three-dimensional ex- ternal and internal airway images have a high sensitivity and specificity compared with rigid bron- choscopy. 1 For dynamic collapse, such as in tra- cheobronchomalacia, inspiratory and expiratory CT imaging may demonstrate the characteristic crescent changes seen with collapse of the poste- rior membrane. Subsequent evaluation is typically done via endoscopy. Defining the injury and assessing the Disclaimer and Financial Disclosures: None. a Thoracic Interventional Program, Division of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 15 York Street, Room 100, Laboratory of Clinical Investigation (LCI), New Haven, CT 06510, USA; b Interventional Pulmonology, Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, University of Colorado, Denver, 1400 Jackson Street, Denver, CO 80206, USA * Corresponding author. E-mail address: [email protected] KEYWORDS Tracheobronchial stenosis Systemic therapy Bronchoscopy Bioabsorbable stenting KEY POINTS Tracheobronchial stenosis results from malignant and benign causes. Treatment includes systemic therapy in addition to endoscopic or surgical approaches. Balloons, heat therapy, and stenting are useful for stenosis involving the proximal airways. These therapies may provide immediate improvement in dyspnea. Surgical resection of limited benign and malignant stenosis has a high success rate and may pro- vide long-lasting results. New surgical therapies, as well as developments in bioabsorbable stenting, hold promise for the future treatment of tracheobronchial symptomatic stenosis. Clin Chest Med 34 (2013) 557–567 http://dx.doi.org/10.1016/j.ccm.2013.05.002 0272-5231/13/$ – see front matter Ó 2013 Elsevier Inc. All rights reserved. chestmed.theclinics.com

Transcript of Tracheobronchial Stenosis · Tracheobronchial stenosis Systemic therapy Bronchoscopy Bioabsorbable...

Page 1: Tracheobronchial Stenosis · Tracheobronchial stenosis Systemic therapy Bronchoscopy Bioabsorbable stenting KEY POINTS Tracheobronchial stenosis results from malignant and benign

Tracheobronchial StenosisCauses and Advances in Management

Jonathan Puchalski, MD, MEda,*, Ali I. Musani, MDb

KEYWORDS

� Tracheobronchial stenosis � Systemic therapy � Bronchoscopy � Bioabsorbable stenting

KEY POINTS

� Tracheobronchial stenosis results from malignant and benign causes.

� Treatment includes systemic therapy in addition to endoscopic or surgical approaches.

� Balloons, heat therapy, and stenting are useful for stenosis involving the proximal airways. Thesetherapies may provide immediate improvement in dyspnea.

� Surgical resection of limited benign and malignant stenosis has a high success rate and may pro-vide long-lasting results.

� New surgical therapies, as well as developments in bioabsorbable stenting, hold promise for thefuture treatment of tracheobronchial symptomatic stenosis.

INTRODUCTION

Airway stenosis may involve the glottis, subglottis(below the vocal cords but above the inferiorcricoid), or tracheobronchial tree. It may be con-genital or acquired, caused by benign or malignantdiseases, focal or diffuse, and present with varioussymptoms. Patients with significant stenosis maypresent with dyspnea, wheezing, or stridor. Stridoroccurs when the airway diameter in an adult dimin-ishes to approximately 6mm.Given that congenitaland pediatric stenosis may often have differentcauses and require different treatments, this articlefocuses primarily on adult stenosis of the tracheo-bronchial tree.

EVALUATION

Beyond the physical examination, evaluation oftenincludes a combination of physiologic, radio-graphic, and endoscopic assessments. Pulmonaryfunction tests may show a delay in reaching peak

Disclaimer and Financial Disclosures: None.a Thoracic Interventional Program, Division of PulmonaSchool of Medicine, 15 York Street, Room 100, Labora06510, USA; b Interventional Pulmonology, Division of PJewish Health, University of Colorado, Denver, 1400 Jack* Corresponding author.E-mail address: [email protected]

Clin Chest Med 34 (2013) 557–567http://dx.doi.org/10.1016/j.ccm.2013.05.0020272-5231/13/$ – see front matter � 2013 Elsevier Inc. All

expiratory flow, a truncation of peak expiratoryand peak inspiratory flow, and/or an abruptdecrease in expiratory flow at the end of expiration.There may be flattening of the inspiratory andexpiratory phases in the presence of fixed upperairway obstruction. A chest radiograph may detecttracheal disease although multiplanar computedtomography (CT) is useful for characterization ofdisease extent, exact configuration, and for plan-ning treatment. This airway CT is different fromneck or chest CT scans with thinner cuts that allowfor three-dimensional reconstruction. Often calledvirtual bronchoscopy, the three-dimensional ex-ternal and internal airway images have a highsensitivity and specificity comparedwith rigid bron-choscopy.1 For dynamic collapse, such as in tra-cheobronchomalacia, inspiratory and expiratoryCT imaging may demonstrate the characteristiccrescent changes seen with collapse of the poste-rior membrane.

Subsequent evaluation is typically done viaendoscopy. Defining the injury and assessing the

ry, Critical Care and Sleep Medicine, Yale Universitytory of Clinical Investigation (LCI), New Haven, CTulmonary, Critical Care and Sleep Medicine, Nationalson Street, Denver, CO 80206, USA

rights reserved. chestm

ed.th

eclinics.com

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Box 1Common causes of tracheobronchial stenosis

Cause of Tracheal or Bronchial Stenosis

Focal inflammation

Tracheostomy

Intubation

Trauma

Burns

After transplant

Systemic inflammation

Wegener granulomatosis

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presence of active inflammation and edema areessential. Bronchoscopic biopsies may secure thepathologic diagnosis. Recent studies demonstratethat measuring lateral airway wall pressure oneach side of the stenosis and plotting pressure-pressure curves can quantitatively assess the siteof maximal obstruction and degree of stenosis.The investigators suggest thesemeasurements es-timate the need for additional procedures morethan bronchoscopy alone and demonstrated thatthe cross-sectional area, dyspnea scale, pulmo-nary function tests, pressure difference, and angleof the pressure-pressure curve improved after in-terventional procedures.2 An understanding of po-tential causes is also required to guide therapy.

Relapsing polychondritis

Sarcoidosis

Amyloidosis

Inflammatory bowel disease

Others

Infectious

Tuberculosis

Aspergillus

Others

Dynamic collapse

Focal malacia

Diffuse tracheobronchomalacia

Miscellaneous

Saber sheath trachea

CAUSES AND PATHOGENESIS

Although dynamic obstruction, such as occurswith vocal cord dysfunction or tracheobroncho-malacia, causes similar symptoms, this articlefocuses on stenosis that is fixed. Tracheobronchialstenosis may be predominantly intraluminal,such as postintubation tracheal stenosis, or fromextrinsic compression, caused by a tumor. Glottic,subglottic, and high tracheal stenosis may requiresignificantly different stabilization and treatmentthan carinal or bronchial stenosis. Furthermore,therapeutic approaches may be different depend-ing on whether the disease is benign or malignant,and the extent of disease. The more common con-ditions causing tracheobronchial stenosis arelisted in Box 1 and shown in Figs. 1 and 2.

Tracheobronchopathiaosteochondroplastica

Broncholithiasis

Idiopathic

Malignancy

Adenoid cystic carcinoma

Squamous cell carcinoma

Lung cancer: non–small and small cell

Metastatic disease

FOCAL BRONCHIAL DISEASES

Both malignant and benign diseases may causefocal narrowing of the tracheobronchial tree. Withinthe trachea, malignancy predominates. Primarytracheal malignancies include squamous cell carci-noma and adenoid cystic carcinoma, amongothers. Non–small cell lung cancer and small celllung cancer are obvious causes of obstructiondue either to extrinsic airway compression, intrinsicairway tumor, or a combination of both. Whenconfined to the trachea ormainstembronchi, surgi-cal resection may be curative. Metastatic diseasefrom a variety of conditions may cause obstructionfrom endobronchial deposits or massive adenop-athy. Breast, colorectal, renal cell, and melanomaare the most common extrathoracic malignanciesto metastasize to the lungs. When the disease isadvanced, various endoscopic modalities maycomplement chemotherapy or radiation therapy.Typically, bronchoscopic management includes acombination of opening the airway (balloons), de-bulking the tumor (heat or cold therapy), and

stabilizing the airway for the longer term (stenting).These treatment modalities are described later.The most common causes of benign iatrogenic

stenosis include intubation, tracheostomy, andlung transplant. Mucosal ischemia followed bygranulation tissue and fibrosis often creates 1.5to 2.5 cm of stenosis after intubation or tracheos-tomy with cuffed tubes.3 With low-pressure cuffsand maintaining a pressure less than 30 mm Hg,the incidence after intubation has decreasedto 1%, whereas after tracheostomy, stenosis

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Fig. 1. Iatrogenic causes of benigntracheal stenosis. (A) Overinflationof the endotracheal tube may leadto mucosal ischemia and subsequentstenosis. Cuffed tracheostomy tubespose a similar risk. Tracheal stenosisfrom these focal insults may looklike that shown in (B).

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approaches 10% to 15% and bronchial anasto-motic stenosis after transplant occurs in up to15%.3

A variable degree of stenosis has been reportedin up to 90% of patients with tuberculosis.3 Airwayinvolvement from tuberculosis likely evolves instages, from submucosal tubercules to ulcerationand necrosis. Subsequent healing can lead tofibrosis, often with long segments of circumferen-tial stenosis. Stenosis of the airways can also

Fig. 2. Examples of benign tracheobronchial stenosis. (A)ning. (C) Endoscopic image of the adjacent mucosal reactBronchial stenosis caused by Wegener granulomatosis. (F) Pstenosis of unknown cause. (H) Sagittal and (I) three-dimen

occur from adjacent lymphadenopathy. Prebron-choscopic sputum results are often negativedespite active disease, and CT findings may benonspecific.4

Aside from tuberculosis, other infectious or-ganisms can cause tracheobronchial stenosis.Klebsiella rhinoscleromatis is an encapsulatedgram-negative bacterium endemic in tropical andsubtropical areas; it causes rhinoscleroma, a slowlyprogressive granulomatous disease. Nodules or

Anthracosis. (B) Broncholithiasis, as shown on CT scan-ion. (D) Tuberculosis with submucosal granulomas. (E)osttransplant bronchial stenosis. (G) Complex webbedsional reconstruction of focal benign tracheal stenosis.

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masses that form in the granulomatous phase maycause partial obstruction (pseudoepitheliomatoushyperplasia) and the final sclerotic phasemay resultin fibrosis. Biopsy or cultures assist in establishingthe diagnosis.4 Fungi, particularly Aspergillus,may cause tracheobronchitis in immunocompro-mised hosts, such as those with AIDS, underlyingmalignancy, or after transplant. Epithelial ulcerationand submucosal inflammationoccurs andmay leadto strictures, whereas deeper bronchial wall necro-sis may lead to bronchial or bronchovascularrupture and death.3

Bronchial anthracofibrosis demonstrates char-acteristic bronchoscopic findings in the absenceof known pneumoconiosis or smoking.3 It is hy-pothesized that the black pigments are derivedfrom anthracotic material in the adjacent lymphnodes, with possible perforation of the nodes orpenetration of carbon particles into the mucosa.Healing with a fibrotic response may lead to bron-chial narrowing or obstruction. A CT scan maydemonstrate mediastinal and hilar lymphadenopa-thy and endoscopy may reveal smooth bronchialnarrowing. Atelectasis may accompany these find-ings. Biopsy should be performed to excludemalignancy.4

Tracheobronchopathia osteochondroplasticaspares the posterior membrane and typically ap-pears as submucosal nodules extending into thetracheobronchial lumen. Histologically, these aresubmucosal osteocartilaginous growths that leavethe mucosal surface intact.5 Treatment options forsevere airway compromise include surgical orlaser resection, radiation, or stent placement.Broncholithiasis typically results from calcifica-

tion of a lymph node caused by previous infectionwith organisms such as Tuberculosis or Histoplas-mosis. The lymph node may erode into the airwayin which case the patient may cough up calcifiedmaterial. Alternatively, the lymph node may causecompression of the airways. Interventional or sur-gical approaches may be necessary dependingon the compromise of the airways.Idiopathic tracheal stenosis occurs almost

exclusively in middle-aged women. A weblike orcomplex stenosis develops mostly in the area ofthe cricoid. Although endoscopic therapy is effica-cious, late recurrences are frequent and the dis-ease requires ongoing follow-up.4

SYSTEMIC DISEASES

Relapsing polychondritis is associated with recur-rent inflammation of cartilaginous structures of thenose, external ear, peripheral joints, and airways.Up to 50% of patients may develop airway involve-ment, often starting at the larynx or subglottic

space and progressing to involve more of thetracheobronchial tree. An inflammatory infiltratedevelops in the cartilage and perichondrial tissue.The ensuing airway inflammation may lead toairway strictures, whereas collapse of the cartilag-inous support may also lead to tracheobroncho-malacia. The diagnosis may be made by meetingspecific clinical criteria, whereas a chest CT maydemonstrate attenuation of the airway walls(classic smooth thickening of anterior and lateralwalls with characteristic sparing of the posteriormembrane). Cartilaginous destruction may leadto the need for tracheobronchial stenting.4

Wegener granulomatosis is characterized bynecrotizing granulomatous vasculitis, which maylead to subglottic, tracheal, or bronchial stenosis.It has been reported that 10% to 20% of patientswith Wegener granulomatosis develop laryngo-tracheostenosis.6 Granulomatous inflammationand vasculitis are seen in the mucosa and sub-mucosa early in the disease, whereas fibrosis en-sues later. Bronchoscopy may demonstrateulcerative tracheobronchitis, inflammatory steno-sis, or noninflammatory stenosis.5 Steroids andimmunosuppressant therapy are the mainstaybut bronchoscopic intervention may be required.Surgery may also be required, including larygno-tracheal reconstruction, albeit with increased riskof postprocedural repeated dilation.6

Bronchial involvement is more common thantracheal involvement in sarcoidosis. Bronchialwall thickening caused by granulomas and peri-bronchial interstitial fibrous tissue may result insmooth or irregular luminal narrowing. Lobar orsegmental bronchial obstruction may occur fromairway wall fibrosis, granulomatous inflammation,or lymph node compression. As with the inflamma-tory diseases described earlier, when systemictherapy fails to control disease, bronchoscopic in-terventions may be required.Tracheobronchial amyloidosis may be present

as an isolated manifestation with tracheal deposi-tion of amyloid, or in conjunction with systemicamyloidosis. Pathologically, the amyloid is depos-ited in proximity to the tracheal gland acini and theblood vessel walls. The glands eventually atrophyand the amyloid produces irregular plaques andnodules in the mucosa. On occasion, massesmay appear (amyloidomas) that may be radio-graphically difficult to distinguish from neoplasms.Biopsies are diagnostic, and Congo Red stainingmay highlight the amyloid. Radiation therapy maysometimes be required in addition to the interven-tional techniques described later.3,5

Rare causes of airway stenosis include inflam-matory bowel disease; either ulcerative colitis orCrohn disease may produce airway inflammation.

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Airway disease may present as ulcerative trache-itis and tracheobronchitis, bronchiectasis, andsmall airway disease such as obliterative bron-chiolitis.4 As with the aforementioned conditions,airway interventions may be required if systemictherapy is insufficient.

VENTILATORY STRATEGIES BEFOREINTERVENTIONS FOR AIRWAY STENOSIS

Flexible and rigid bronchoscopy are performed toevaluate and treat airway stenosis. Whereas theflexible scope can be inserted in an unventilatedpatient, via a laryngeal mask airway or throughthe endotracheal tube, it contributes to obstructionbecause of its size. The rigid bronchoscope re-quires general anesthesia but allows ventilationthrough its side port. Intravenous short-actingagents such as remifentanil and propofol may becombinedwith narcotics, neuromuscular blockers,or inhaled agents during induction and throughoutthe procedure while maintaining strict airwaycontrol. With mid tracheal lesions, a decrease inrespiratory rate or exhalational times may benecessary to minimize inspiratory pressures.

Many anesthesiologists use jet ventilation at low(20 breaths/min) or high (150 breaths/min) fre-quency. This may be performed with a catheterthrough the rigid bronchoscope, a laryngoscope,and a small (eg, 5.0 mm) endotracheal tube, oreven via a transcricothyroid membrane catheter.7

A series of 44 patients with severe upper airwayobstruction demonstrated successful ventilationafter transtracheal catheters placed under localanesthesia via the cricothyroid membrane orbelow the first or second trachea rings. Althoughminor complications occurred infrequently, theydid not experience the major pressure-relatedproblems reported elsewhere (pneumothorax,massive surgical emphysema, pneumomediasti-num, and cardiovascular instability). The anes-thesiologists adjusted the driving pressure orfrequency when higher pressures were observed.8

Other techniques include high-frequency positivepressure ventilation, high-frequency oscillatoryventilation, or cardiopulmonary bypass if adequateoxygenation cannot be maintained.

BRONCHOSCOPIC INTERVENTIONS FORAIRWAY STENOSIS

As mentioned earlier, the therapeutic options forairway stenosis depend on the cause of theobstruction. Patients with systemic diseases andclinically significant airway stenosis, benign yetinoperable disease, or advanced malignancymay require bronchoscopic interventions. Various

bronchoscopic techniques are possible to relievethe obstruction. Although these procedures areexpected to have an immediate impact when theappropriate patient is selected, long-term follow-up is essential to monitor the response to treat-ment and determine whether repeat proceduresare necessary. This section focuses on airway bal-loons, heat modalities, and bronchial stenting toprovide immediate relief for significant stenosis.

Airway dilation may be accomplished throughrigid and flexible bronchoscopy. The rigid bron-choscope may core through areas of stenosiswith the shear mechanics of the rigid scopeproviding dilation. A metal bougie dilator providesa similar effect. When this is not possible, balloonexpansion may be useful. The benefits of balloonsinclude the avoidance of surgery and other sophis-ticated techniques or equipment. Compliant bal-loons, such as the angioplasty balloon catheter(Fogarty), may be best for a fleshy or necrotic intra-luminal tumor that easily compresses. More rigidballoons, such as the controlled radial expansion(CRE) balloon (Boston Scientific) may be used todilate tight areas of stenosis. These balloonsexpand from 6 mm to 20 mm (using differentballoon catheters) while being manually inflated.Care must be taken to avoid tearing the airwaysor rupturing them by using too large a balloon orcareless dilation. In a recent study, patientsdemonstrated a subjective improvement in symp-toms as well as 1-month sustained improvementin pulmonary function tests. However, for thosewho required more than 1 procedure, mostrequired stenting. Combining their results with aliterature review encompassing 340 patients and554 balloon dilation procedures, the processesmost amenable to balloon dilation were thosewith fixed stenosis; those with active inflammation,calcification, carcinoma, or in whom the surround-ing cartilage was destroyed (malacia) were lessresponsive.9

Ablative techniques are frequently used to rees-tablish airway patency. These include heat andcold therapies. Circumferential weblike stenosismay benefit from incisions with an electrocauteryknife (Fig. 3). Imagining the face of a clock, 3 smallincisions (at 9 o’clock, 12 o’clock, and 3 o’clock)can be made with the knife and subsequentballoon dilation performed. The knife creates 1-to 2-mm incisions generating weak points suchthat the balloon will dilate the airway with targetedrather than sporadic and uncontrolled mucosaltearing. Recent analysis of the reusable electrodeknife in the cut mode demonstrated improvedsymptoms, improved pulmonary function tests,and less fibrin production than laser therapy in asimilar group of patients. Less than half of the

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Fig. 3. Treatment options for tracheal stenosis. (A) Electrosurgical knife applied at the 3 o’clock position. (B) Re-sults of cautery to reopen suprastomal stenosis. (C) Angioplasty balloon dilation. (D) The more rigid CRE balloondilation. (E) Inflammatory tracheal stenosis. (F) This unique stenosis was treated with a hybrid stent before sur-gical resection. (G) Complete stenosis of the subglottic space. (H) Silicone stent after reestablishing patency.

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patients in this small analysis required repeat inter-vention for weblike stenosis.10

Additional heat modalities used for treatmentof tracheobronchial stenosis include electrocau-tery, argon plasma coagulation (APC) and lasertherapy. These techniques are discussed else-where in this issue on interventional pulmonologyand thus discussion here is kept brief. With cau-tery, an electric current is used to generate heat.Several devices may be used to apply this current,including the knife, a probe, and snare/cuttingloop. Unlike the knife described earlier, the probeis blunt. The user sets the wattage (eg, 20–40 W)and depth of penetration; these combined withthe time of topical impact determine the depth ofmucosal destruction. In contrast, APC uses anargon gas charged with an electric current toachieve thermal tissue destruction. The argongas flows flexibly around angles such that APC issuitable for bronchial segments that take off atacute angles to major airways. APC is a noncon-tact mode of thermal coagulation and as such,helps clear blood and mucus while performing su-perficial coagulation. Cerebral gas embolism hasbeen reported as a unique complication of thisprocedure. Both electrocautery and APC offer ad-vantages of ease and lower cost compared withlaser therapy.11

The most common type of lasers used in theairways are the neodymium–yttrium-aluminum-garnet (Nd-YAG) and carbon dioxide (CO2)lasers. The Nd-YAG provides tissue vaporization

and coagulation. It has deeper thermal energythan the CO2 laser and may penetrate up to10 mm.12 The CO2 laser has more precise cuttingabilities. The development of the flexible fiber CO2

delivery system allows for the flexible broncho-scope to be used to ablate and cut with this laser.This contrasts with the typical microscope-mounted CO2 laser, which requires general anes-thesia. The laser is typically in pulse mode at 5 to10 W delivered to 2 to 3 wedges separated bytissue to avoid circumferential mucosal denuding.Postoperative dexamethasone may be given tominimize upper airway edema when this ablationis performed high in the airway.13 All heat thera-pies require that a patient receive less than 40%inspired oxygen to avoid airway fires during theprocedure.Mitomycin C may be an adjunct to radial in-

cisions made with laser or cautery. Pledgets ofcotton soaked in mitomycin C are topicallyapplied to the areas of stenosis. This is believedto impede the inflammatory response.14,15 A pro-spective, randomized, double-blind placebo-controlled trial of 26 patients with laryngotrachealstenosis of various causes suggested that 2 ap-plications 3 to 4 weeks apart delayed but didnot prevent the recurrence of stenosis in benigndisease.15 A retrospective analysis of 67 pro-cedures in 36 patients also demonstrated alonger symptom-free interval than when endos-copy was used without mitomycin C.16 To ourknowledge, there is no Cochrane review or

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meta-analysis of the effects of mitomycin Cand thus its use requires further investigationbefore claiming efficacy.

In contrast to heat and medical therapies, con-tact and spray cryotherapy have been described.Contact cryotherapy uses a probe wherebyextreme cold is alternated with internal body tem-perature to create a freeze-thaw cycle. Its efficacyis debatable as results have been variable. Spraycryotherapy uses a 7-French catheter and nitrogenas a base cryogen. Approximately 25W (J/s) of en-ergy is transferred, similar to laser therapy, butthere is no risk of airway fire with the latter. Earlyresults with spray cryotherapy are encouragingbut further studies are needed to document itsefficacy and safety.17

Airway stenting is an important strategy for man-aging various types of tracheobronchial obstruc-tion. Stents are also discussed in other articles inthis issue. Airway stenting may be used eithertemporarily or chronically. Several different typesof stents exist (see Fig. 3), although metal stentshave a US Food and Drug Administration blackbox warning for benign disease in part becauseof their predisposition to form granulation tis-sue. For benign conditions, silicone stents arepreferred. These stentsmay be tubular, a Y-config-uration that covers portions of the trachea andmainstem bronchi, an hourglass configurationwith wider ends and a narrower center, or may becustomized. On the other hand, metal stents aretubular. The advantage of metal stents is that, un-like silicone stents, they can be placed with theflexible bronchoscope. The metal stents may becompletely covered, partially covered, or uncov-ered. Metal stents are more expensive than sili-cone stents. Both are susceptible to migration,granulation tissue formation, mucus plugging,and other complications.

Practice management varies, but any patientwho has a stent placed requires appropriatefollow-up. The duration a stent should remain inplace is not known and likely depends on the clin-ical scenario. Patients with malignant stenosisoften die with the stent in place; benign stenosismay require long-term placement. Factors pre-dicting the ability to remove stents in tuberculosisincluded the lack of complete lobar atelectasisand performing stent placement within 1 monthof the development of any atelectasis. Stentswere left in place for 12.5 months in those pa-tients whose stenosis was successfully treatedby the temporary silicone stent.18 A patient withrelapsing polychondritis and a silicone stent for16 years has been described recently.19 Thus,the exact duration of stent placement varies ac-cording to each patient.

RESULTS OF AIRWAY INTERVENTIONS

For idiopathic tracheal stenosis, initial success ishigh, but recurrence is typical. In a retrospectivestudy of 23 patients with idiopathic stenosistreated at 9 institutions, the stenosis recurred in30% of patients at 6 months, 59% at 2 years,and 87% at 5 years. A combination of therapieswas frequently used.20 Improvements that resultfrom airway interventions in malignant diseaselikely deserve distinction from interventions forbenign disease because of the systemic effectsof cancer. A few studies have investigated qualityof life and dyspnea after airway interventions forcancer. Amjadi and colleagues21 used the vali-dated European Organization for Research andTreatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30) and included 20 patients over6 months. Using a combination of the therapiesdescribed earlier, more than 80% of airway caliberwas restored in 80% of patients and 85% of pa-tients demonstrated an improvement of dyspneascores at 24 hours that extended to 30 days.Quality-of-life response was variable, likelybecause of the impact of symptoms such as painfrom metastases and other factors that are notinfluenced by airway therapy. A separate retro-spective cohort study of 37 patients with high-grade symptomatic central airway obstructionevaluated exercise capacity, lung function, andquality of life. More than 90% of patients hadrestoration of airway patency (>50% of airwayrestored). Statistically significant improvements inthe 6-minute walk test were noted up to180 days. Dyspnea scores, resting Borg, forcedexpiratory volume in 1 second, and forced vital ca-pacity were improved at day 30. An improvementin quality of life was seen in 43% of patients. Themedian survival was 166 days and the 6-monthsurvival rate was 46%.22

FUTURE ENDOBRONCHIAL THERAPY

Biodegradable airway stents are under investiga-tion and have been placed in humans. Polydioxa-none is a semicrystalline biodegradable polymerthat has some shape memory and degrades overtime by random hydrolysis. The degradation timehas not been exactly defined. Four childrenreceived 11 polydioxanone tracheal stents and3 of the 4 are alive and in good clinical condition12 months after the first stents were placed.It was difficult to predict the amount of radialforce needed to maintain an airway withoutcausing granulation tissue or creating risks forerosion, and to predict the rate of degradation.23

Twenty biodegradable stents have been placed

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in 6 patients after lung transplant who developedbronchial stenosis at the anastomosis. Thesestents were also made of polydioxanone; 5 of the6 patients were alive and intervention free up to44 months after the first stent was placed.24

Various ongoing studies in animal models of thisand other materials (polycaprolactone25) maylead to clinically applicable biodegradable airwaystents in the future.

SURGICAL MANAGEMENT

Surgery is possible for localized malignancy aswell as benign stenosis that affects less than halfof the trachea. The aforementioned interventionalprocedures may play an important preoperativerole to establish airway patency and enhancesafety and ease of perioperative ventilation. Otherpreoperative interventions include aggressivetreatment of gastroesophageal reflux, evaluatingfor the presence of aspiration, and preoperativetreatment of patients colonized with methicillin-resistant Staphylococcus aureus.

The location of stenosis may dictate the type ofsurgical procedure performed. The main types oftherapeutic procedures for subglottic stenosisinclude laryngotracheal resection and anasto-mosis, laryngoplasty without segmental resectionand with or without bone or cartilage grafting, orendoscopic procedures. The Cotton-Meyergrading scale describes the degree of stenosisand resection is accomplished using a single-stage laryngotracheal reconstruction (LTR) ordouble-stage LTR procedure. Cricotrachealresection may be performed when the larynx isspared.26 Pearson described the technique of an-terolateral cricoid cartilage resection and primarythyrotracheal anastomosis with preservation ofthe recurrent laryngeal nerve in 1975. Grillow sub-sequently described the use of a flap of posteriormembranous trachea in cases of circumferentialsubglottic stenosis.27 A recent meta-analysisdemonstrated that laryngotracheal resection wasmore effective than the other 2 techniques, espe-cially in the absence of glottic involvement. Therandom-effect pooled success rate of LTR wasgreater than 95%, that of laryngoplasty was76%, and that of endoscopy highly variable(40%–82%). The investigators concluded that lar-yngoplasty is suitable for resection of long seg-ments or subglottic stenosis with glottisinvolvement. Patients with less than 1 cm of steno-sis and without framework destruction may bereasonable candidates for endoscopic manage-ment as a first modality, with surgery reservedfor failure.28

Significant advances in tracheal surgeryoccurred in the 1950s and refinements in the tech-niques led to resection of longer segments. Themain principles of resection include meticulousdissection to preserve the blood supply of the tra-chea and recurrent laryngeal nerves, as well asavoidance of excessive anastomotic tension. Aswith laryngotracheal involvement, the types oftracheal surgery depend on the location of the ste-nosis. Cotton and Fearon introduced the costalcartilage augmentation procedure in 1976 thathas become known as LTR and other open tech-niques have been adopted, including the anteriorcricoid split, tracheal resection with end-to-end re-anastomosis, and slide tracheoplasty.1

In slide tracheoplasty, a long stenotic segmentis divided transversely at its midpoint and the up-per and lower stenotic segments divided longitudi-nally, anteriorly, and posteriorly. The splayedupper and lower segments are then slid togetherto produce a trachea with quadrupled cross-sectional area.29

Tracheal resection with reanastamosis is seenas a procedure of choice given its high successrate (71%–95%) and minimal morbidity.30 It canbe accomplished using a neck collar incision forhigh stenosis or median sternotomy for mid tolower tracheal stenosis. After dissection from thesurrounding tissue, reanastomosis may be end-to-end tracheal, cricotracheal, or thyrotracheal,depending on the location of the stenosis. Securingsutures between the skin of the chin and anteriorchest may maintain neck flexion to avoid excesstension at the anastomosis during the early preop-erative period.31 Early extubation, avoidance ofsystemic corticosteroids, and use of absorbablesubmucosal sutures may limit complications.30

Pericardial patches, rib grafting, and other tech-niques have also been described to facilitateresection. Over 40 years and 503 patients withpostintubation stenosis, results were good in87.5%of patients. All benign and 70%ofmalignanttumors were resectable. Recent perioperativemortality was 3% and anastomotic complicationsoccurred in 15%. Multivariate analysis demon-strated that length of resection, diabetes, redo re-sections, laryngeal involvement, pediatric age,and presence of tracheostomy were importantprognostic factors for complications.32

Further distally into the airways, carinal resec-tions are feasible although complicated. Typically,either a median sternotomy or right thoracotomy isperformed and the neocarina is fashioned from the2 divided main bronchi. The longer bronchus isusually anastomosed end to end with the tracheaand the shorter bronchus attached to the sidewall

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of the longer bronchus with end-to-end anasto-mosis. Bronchial resections for malignant orbenign stenosis are also performed. A bronchialsleeve resection begins with bronchotomy of theproximal airway followed by anastomosis withthe lower airways. The diseased segment isremoved, tension-free anastomosis is attempted,and occasional pedicled pleura or pericardiumcan be used between the bronchial anastomosisand vasculature.33

FUTURISTIC SURGICAL APPROACHES

Autografts, allografts, bioengineered tracheal plat-forms, and tracheal transplants may becomemoreprominent in the future. The innate complexity andcompromising blood supply of the trachea make asingle tissue graft of the trachea rarely sufficient toachieve adequate function. Autografts include apatient’s own tissue to reconstruct the airways;for example, resection of bronchi and replacementin the trachea, or muscle flaps to bridge defects re-sulting from tracheobronchial reconstruction. Thegrafts must have rigidity, epithelium, and adequatevascular supply.

Seguin and colleagues34 demonstrated thatfunctional tissue could be regenerated in sheepafter replacement of the trachea with a cryopre-served aortic allograft. The use of cryopreservedspecimens would offer advantages for use in tis-sue banks, for permanent storage, and by limitingthe need for immunosuppression. It has beenshown that respiratory epithelial cells and cartilagecan regenerate in animal models of aortic allo-grafts and that the allograft progressively trans-forms into a structure resembling tracheal tissue.Airway stenting was mandatory in pigs to preventcollapse of the initially compliant graft, and theinvestigators concluded that long-term stentingwas necessary to provide stability as the neotra-chea formed.35 Tracheal replacement using bio-absorbable scaffolds36 have been described.These studies are still mostly limited to animals.

Composite tissue grafts may include costalcartilage for support, mucosal grafts (buccal, pal-ate) for epithelium, and pedicled flaps or free tis-sue transfer flaps for blood supply. Prostheticscaffolds, such as a mesh, have been combinedwith free tissue flaps in advanced efforts to recon-struct the airway. An overview of unique surgicalapproaches to tracheal reconstruction is recom-mended.37 A tissue-engineered tracheal allografthas been described, using a cadaveric trachea de-cellularized and with human leukocyte antigensremoved, and with autologous bronchial epithelialcells harvested, cultured, and implanted on the

internal surface of the trachea. Bone marrow–derived mesenchymal stem cells were harvestedand differentiated toward chondrogenesis and im-planted on the external surface of the trachealgraft. Although it revascularized well, there areconcerns about the dependability of neovasculari-zation of free grafts.37

Tracheal transplant is a challenge because ofthe vascular supply of the trachea, constant move-ment of the trachea, and constant exposure tobacteria. Only a few reports of tracheal transplantexist. The current concepts of tracheal transplan-tation include vascularization, growth of epithe-lium, and use of a chimeric product that includesdonor tissue (cartilage, respiratory mucosa) andrecipient tissue (membranous trachea, forearmfascia, forearm skin, and buccal mucosa). In thisapproach, the donor trachea is implanted in theforearm and allowed to vascularize, then epithe-lialized with recipient mucosal graft, and ultimatelytransposed into the trachea. Immunosuppressantsare gradually withdrawn to allow anastomotic re-population of recipient blood vessels and respira-tory epithelium, and the recipient buccal mucosaand recipient forearm blood vessels preserve theairway lumen in the mid portion. This fascinatingwork is well worth reading.38

SUMMARY

Tracheobronchial stenosis results from malignantand benign causes. Treatment includes systemictherapy in addition to endoscopic or surgical ap-proaches. Balloons, heat therapy, and stentingare useful for stenosis involving the proximal air-ways. These therapies may provide immediateimprovement in dyspnea. Surgical resection oflimited benign and malignant stenosis has a highsuccess rate and may provide long-lasting results.New surgical therapies, as well as developmentsin bioabsorbable stenting, hold promise for thefuture treatment of tracheobronchial symptomaticstenosis.

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