ARTICLE IN PRESS

www.icvts.org

doi:10.1510/icvts.2010.238196

Interactive CardioVascular and Thoracic Surgery 11 (2010) 425–428

� 2010 Published by European Association for Cardio-Thoracic Surgery

New

IdeasInstitutional

ReportW

orkin

ProgressReport

ESCVSArticle

NegativeResults

State-of-the-artBest

EvidenceTopic

BriefCom

munication

CaseReport

Follow-up

PaperEditorial

ProtocolProposalfor

Bail-out

ProcedureN

omenclature

HistoricalPages

Institutional report - Pulmonary

Outcomes of airway stenting for advanced lung cancer with centralairway obstruction

Hisashi Saji *, Kinya Furukawa , Hidemitsu Tsutsui , Masahiro Tsuboi , Shuji Ichinose , Jitsuo Usuda ,a, b a a a a

Tatsuo Ohira , Norihiko Ikedaa a

Department of Thoracic Surgery and Oncology, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japana

Department of Thoracic Surgery, Kasumigaura Hospital, Tokyo Medical University, 3-20-1, Chuo Ami-machi, Inashiki-gun, Ibaraki 300-0395, Japanb

Received 17 March 2010; received in revised form 14 June 2010; accepted 29 June 2010

Abstract

Approximately 30% of lung cancer patients will develop central airway obstruction (CAO). Interventional therapeutic bronchoscopyincluding airway stenting (AS) providing immediate and effective palliation is therefore essential to improve quality of life (QoL). However,no report has demonstrated the survival benefit of AS. We retrospectively reviewed 65 patients with CAO due to lung cancer who underwentAS from June 1994 to May 2008. Seventy-nine stents were required. Silicon, metallic, or both stents were placed in 42 (60%), 19 (29%), oreight (11%) patients, respectively. Single stent was required in 53 (83%) patients, double in 10 (14%), and triple in two (3%). AS couldprovide acute relief of central airway and significant improvement was seen in 98% of patients. Fifty-nine patients with detailed observationswere assessed further. Morbidity and mortality rates were 22% and 8%, respectively. AS resulted in 25.2% of one-year survival rate and6.2 months of median survival time (MST). AS followed by adjuvant therapy provided a four-month increase in MST, although overall survivalwas not significantly changed. This study represents a single-institution experience. Although an aggressive strategy of AS is justified inorder to improve symptoms and QoL, AS itself did not contribute to survival benefit.� 2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.

Keywords: Airway stenting; Interventional therapeutic bronchoscopy; Central airway obstruction; Lung cancer

1. Introduction

Approximately 30% of patients with lung cancer will devel-op central airway obstruction (CAO) w1–3x. The gold stan-dard treatment for airway obstruction is surgical resectionand reconstruction. However, most patients with CAO dueto lung cancer are poor surgical candidates on the basis ofeither physiological or oncological criteria. Interventionaltherapeutic bronchoscopy (ITB) providing immediate andgratifying palliation is therefore essential to improve thequality and length of life. ITB includes mechanical core-out of tumor, laser vaporization, photodynamic therapy,brachytherapy, cryotherapy, electrocautery and airwaystenting (AS). In particular, AS can provide immediate,durable and stable airway patency resulting in reliable andprolonged relief of airway symptoms. Management of malig-nant airway disease requires comprehensive and accurateevaluation of resectability by general thoracic surgeons.Palliative therapy is reserved for unresectable patients.The optima management of these patients with CAOincludes the use of radiotherapy, laser therapy, photody-namic therapy and AS. Therefore, in 1994, we establishedan airway interventional bronchoscopy program for themanagement of CAO in the Division of Thoracic Surgery at

*Corresponding author. Tel.: q81-3-3342-6111 ext. 5070; fax: q81-3-3349-0326.

E-mail address: saji-q@ya2.so-net.ne.jp (H. Saji).

Tokyo Medical University. Over the past 15 years, we per-formed 361 ITBs for 283 patients with CAO due to benignor malignant disease. In the current study, we retrospec-tively reviewed all these patients and especially focusedon 59 patients with CAO due to advanced lung cancer toperform a detailed analysis on the effectiveness of AS.

2. Patients and methods

2.1. Patients

Two hundred and eighty-three patients who underwentITBs for CAO from June 1994 to May 2008 were retrospec-tively reviewed in this study with the approval of theInstitutional Review Board. Access to patients’ medicalrecords was approved by Tokyo Medical University andpatients’ confidentiality was maintained.

2.2. Interventional therapeutic bronchoscopy

Indications of ITB included known unresectable malignantCAO, the development of lobar collapse during or aftertreatment, acute or subacute changes in respiratory statusnot otherwise explained, or evidence of endobronchialdisease amenable to palliation. All ITBs were performed ina laser and fluoroscope-equipped operation room. Rigid andflexible bronchoscopy was performed in almost all patients.

ARTICLE IN PRESS

426 H. Saji et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) 425–428

Fig. 1. Distribution and rate of metallic or silicon stent replacement (ns79).T, trachea (ns14; 7 metallic and 7 silicon); C, carina (ns28; 5 dynamic and23 silicon Y); RM, right main bronchus (ns17; 6 metallic and 11 silicon);LM, left main bronchus (ns17; 15 metallic and 2 silicon); TIM, trunchusintermedius (ns4; 2 silicon and 2 metallic); *Dynamic stent.

Details of airway preparation for AS by dilation or coringout a tumor have also been previously described w4–6x.Briefly, mechanical debulking using the tip of the rigidbronchoscope was first carried out followed by laser abla-tion or balloon dilation of the residural tumor using Nd:YAGlaser (KTPyYAG Surgical Laser System, Laserscope, SanJose, CA, USA), argon plasma coagulation (APC300 andICC200; ERBE, Tubingen, Germany) and microwave (Micro-taze, Alfresa, Tokyo, Japan) or balloon dilation (CRE fixed-wire balloon dilators, Boston Scientific, Natick, MA, USA).

2.3. Airway stenting

AS was considered in patients in whom it was impossibleto restore more than 50% of the lumen even after airwaydilatation or who required repeated airway dilatation w4x.Two-thirds of the stents used in this series were siliconerubber (Dumon, Novatech, Aubagne, France) with externalstuds. Y stents (Dumon, Novatech, Aubagne, France) werealso surfaced with studs, but these were predominatelyheld in place by their geometry at the carina. Self-expand-able metallic stents, Ultraflex (Boston Scientific, Natick,MA, USA) and Spiral Z (Medico’s Hirata, Tokyo, Japan) wereused when there was difficulty in stably placing a siliconestent, extreme extrinsic compression resulting in siliconestent migration, or inability to place a large enough siliconestent into the airway.

2.4. Follow-up and assessment

Patients were extubated at the end of the procedure andusually discharged within a week after bronchoscopicassessment. Airway humidifications by an ultrasonic nebu-lizer and medication of tranilast, an antiallergic drug sup-pressing granulations were usually used during hospi-talization and after discharge. Patients underwent broncho-scopy approximately every one to six months. Nearly 40%of patients were referred from other institutions and mostpatients had advanced and terminal disease, which limitedthe practicality of returning to our institute for follow-upcare. Details of the stent procedure, availability and prog-nosis were obtained from the operative notes, medicalrecords and office charts in our institutions or discussions,or a combination of these with the patients, their family,or referring physicians.

The survival curve was estimated using the Kaplan–Meiermethod. Differences between survival curves were comput-ed with the log-rank test. A P-0.05 was considered statis-tically significant (StatView 5.0 SAS Institute Inc, Cary, NC,USA).

3. Results

3.1. Airway stenting for advanced lung cancer

One hundred and ten ITBs were performed in 93 lungcancer patients with CAO in this period. Of these 93patients, 65 (69%) patients required 79 airway stents duringITB. Silicon, metallic, or both types of stents were placedin 42 (60%), 19 (29%), or eight (11%) patients, respectively.The number of stents required in a patient was single in 53(83%) patients, double in 10 (14%) patients, and triple in

two (3%) patients. Fig. 1 shows the distribution and typeof 79 stent placed in this series. Twenty-eight (36%), 17(22%), 16 (21%), 14 (18%), and four (5%) stents were placedin the carina, left main bronchus, right main bronchus,trachea, and truncus intermedius, respectively. In airwayobstruction at the carina position, we usually used siliconY stents (82%), otherwise dynamic Y stents (18%). Siliconstents tend to be used in the right main bronchus, whilemetallic stents tend to be used in the left in this series.

Because 39% of patients in this series were referred fromother institutions, the practicality of returning to ourinstitute for follow-up care was limited. In addition,patients with low grade malignant tumor were excluded inthe further analysis of prognosis. Therefore, 59 (90%) of 65patients were then extracted for further analysis includingsurvival, morbidity, and mortality. As shown in Table 1,there were 51 male and eight female patients, ranging inage from 42 to 91 years with a mean of 63.9 years. Thehistological classification was 30 squamous cell carcinoma,20 adenocarcinoma, four large cell carcinoma, three smallcell carcinoma and two unclassified carcinoma. The distri-bution of clinical staging or patient status at the time ofAS demonstrated that most of patients were stage IIIyIVterminal cases, postoperative recurrence or refractory totheir previous treatment.

AS were performed in 59 advanced lung cancer patientswith CAO with no intraoperative death, however percuta-neous cardiopulmonary support (PCPS) was initially pre-pared or required in five (8.5%) cases. AS has the abilityto provide acute relief of central airway is remarkably

ARTICLE IN PRESS

427H. Saji et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) 425–428

New

IdeasInstitutional

ReportW

orkin

ProgressReport

ESCVSArticle

NegativeResults

State-of-the-artBest

EvidenceTopic

BriefCom

munication

CaseReport

Follow-up

PaperEditorial

ProtocolProposalfor

Bail-out

ProcedureN

omenclature

HistoricalPages

Table 1. Demographics of 59 advanced lung cancer patients undergoing air-way stenting

Mean age (range), years 63.9 (42–91)Maleyfemale 51y8Performance status

0–2y3–4 44y4Unknown 11

HistologyAdenocarcinoma 20Squamous cell carcinoma 30Large cell carcinoma 4Small cell carcinoma 3Undifferented carcinoma 2

Clinical stage or statusIIIyIV 13y3Postoperation 8Refractory to treatment 35

Severe complications 13 (22%)Severe mucus 6Idiopathic pneumothorax 3Idiopathic pyothorax 2Esophageal stenosis 1Acute pulmonary distress 1

Operation-related or hospital death 5 (8%)

Fig. 2. (a) Survival curve of all this series, (b) survival comparison of patientswith airway stenting followed by adjuvant treatment or not.

effective, and significant improvement can be seen in 98%of patients. However, severe complications from stentingoccurred in 13 patients, including severe mucus retentionrequiring bronchoscopic toilet repeatedly (ns9), idiopathicpneumothorax (ns3), idiopathic pyothorax (ns2), esoph-ageal stenosis requiring balloon dilation (ns1) and acutepulmonary distress required mechanical ventilation (ns1).Five of 59 patients died within 30 days or could not bedischarged after the stenting procedure due to operation-related, disease progression or refractory to adjuvant treat-ment of lung cancer. Therefore, AS related morbidity andmortality rate in this series was 22% and 8%, respectively.In addition, two outpatients had late death on 32 days orfive months later because of airway perforation andhemoptysis.

Survival curve of this series was demonstrated in Fig. 1,which results in 25.2% of one-year survival rate and6.2 months of median survival time (MST). As shown inFig. 2, these patients in this series were classified by fourgroups according to the clinical course before and afterAS. AS is a palliative procedure intended to improve symp-toms of CAO. Forty-one percent of patients were able toreceive adjuvant treatment including chemotherapy andyor radiotherapy after AS. Fig. 2b shows that while MST ofpatients with adjuvant treatment after AS was longer thanthose without, the difference was not statistically signifi-cant (Ps0.16).

4. Discussion

Both patients with benign or malignant airway obstructionsuffer from disabling dyspnea, obstructive pneumonia andimpending suffocation. ITB may provide immediate andgratifying palliation that can rescue the patients fromimminent death and assure an improvement in quality oflife (QoL). Of the 283 patients who underwent 361 ITBs inour cohort, 71% of which were for malignant disease the assame as previous reports. The leading cause of CAO requir-ing ITB is lung cancer (31%) followed by thyroid cancer

(27%), and esophageal cancer (7%). As shown in Table 1,major histological types of lung cancer were squamous cellcarcinoma and adenocarcinoma. Most of the patients havelimited prognosis because of advanced stage disease or hadbeen refractory to a conventional therapy.

ITB including mechanical core-out of tumor, laser vapori-zation, photodynamic therapy, brachytherapy, cryotherapy,and electrocautery is itself effective for some patients withintrinsic and extrinsic compression of the tumor; however,results are not always sustainable. AS is a palliative pro-cedure intended to provide durable and stable improve-ment of CAO by keeping airway patency. Therefore, 65patients with advanced lung cancer in our series required79 airway stents. There is no report which addressed adetail of distribution and type of stent placed in advancedlung cancer cases. In our series, silicon, metallic, or bothtypes of stents were placed in 42 (60%), 19 (29%), andeight (11%) patients, respectively. Fig. 1 shows that 36%,22%, 21%, 18%, and 5% of all stents were placed in thecarina, left main bronchus, right main bronchus, trachea,and trunchus intermedius, respectively. At the carina posi-tion, we usually used silicon Y stents (82%), otherwise weused dynamic Y stents (18%). Silicon stents tend to be usedin right main bronchus, while metallic stents tend to beused in left in this series. The development of self-expand-ing nitinol stents are reported to have improved complica-tions previously reported and have advantages including

ARTICLE IN PRESS

428 H. Saji et al. / Interactive CardioVascular and Thoracic Surgery 11 (2010) 425–428

Fig. 3. Clinical courses before or after airway stenting in 59 lung cancerpatients. (a) Airway stenting alone (ns6), (b) airway stenting followed adju-vant treatment (ns10), (c) previous treatment and stenting followed byadjuvant treatment (ns14), (d) previous treatment and airway stenting,BSC, best supportive care.

less migration, dynamic expansion, and simple insertion w7,8x. Recently, self-expanding nitinol stents with a thin siliconcover have also become available, which are designed toprevent or inhibit tissue ingrowth through the body of thestent. In general, uncovered metallic stents are used inpatients with predominantly extraluminal compression,while silicone-covered metallic stents may be favored inpatients with intraluminal tumors.

There are several reports detailing the results of AS formalignant CAO w5, 8–14x. Although significant improvementof symptoms was clearly reported, no report could dem-onstrate the survival benefit for malignant disease. Weunderstand that it is difficult to assess the true survivaleffect of AS, because most patients in our series arereferred from outside and are usually managed in a tertiaryreferral center with limited follow-up data. MST was6.2 months, and one-year survival was only 25.2% in ourseries (Fig. 3a), this would not be unexpected in thispopulation of patients with advanced stage or refractoryto conventional therapy. AS can provide effect acute reliefof CAO in palliation and also often plays a role as a bridgeprocedure to additional therapy. Only when it employs anadditional therapy and yields an anti-tumor effect could ittheoretically provide a survival benefit. Forty-one percentof patients in our series received some form of adjuvanttreatment, while 59% of patients had exhausted all thera-pies and had received no additional therapy (Fig. 4). Someadded but not statistically significant survival benefit of ASwas documented in those patients who did receive adjuvanttherapy. The combination treatment of AS followed byadjuvant treatment provided a four-month increase inmedian survival, although overall survival was not changed(Fig. 3b). Our criteria of adjuvant therapy following AS isbased on patients with advanced stage and a refractorystatus that extended their survival by at least three months.According to the American Society of Clinical Oncology

Clinical Practice Guideline w15x, a platinum-based two-drugcombination of cytotoxic drugs is recommended for patientswith a performance status of 0 or 1 and a single cytotoxicdrug is sufficient for patients with performance status of2.

This study represents a single-institutional experience.Particularly, we focused on advanced lung cancer patientswho underwent AS and demonstrate the possibility ofsurvival benefit of AS followed by adjuvant therapy.Although an aggressive strategy of AS is justified in orderto improve the symptoms of airway obstruction and toimprove QoL in patients with malignant CAO, AS itself doesnot contribute a survival benefit. Therefore, it is importantthat AS plays a crucial role as a bridge to surgery and it isnecessary for the development of effective adjuvanttherapy.

Acknowledgements

The authors are indebted to J. Patrick Barron of theInternational Medical Communication Center of Tokyo Med-ical University for his review of this manuscript.

References

w1x Chin CS, Litle V, Yun J, Weiser T, Swanson SJ. Airway stents. Ann ThoracSurg 2008;85:S792–S796.

w2x Stohr S, Bolliger CT. Stents in the management of malignant airwayobstruction. Monaldi Arch Chest Dis 1999;54:264–268.

w3x Venuta F, Rendina EA, De Giacomo T, Mercadante E, Francioni F, PuglieseF, Moretti M, Coloni GF. Nd:YAG laser resection of lung cancer invadingthe airway as a bridge to surgery and palliative treatment. Ann ThoracSurg 2002;74:995–998.

w4x Tsutsui H, Kubota M, Yamada M, Suzuki A, Usuda J, Shibuya H, MiyajimaK, Sugino K, Ito K, Furukawa K, Kato H. Airway stenting for thetreatment of laryngotracheal stenosis secondary to thyroid cancer.Respirology 2008;13:632–638.

w5x Stephens KE Jr, Wood DE. Bronchoscopic management of central airwayobstruction. J Thorac Cardiovasc Surg 2000;119:289–296.

w6x Wood DE. Bronchoscopic preparation for airway resection. Chest SurgClin N Am 2001;11:735–748.

w7x Vinograd I, Klin B, Brosh T, Weinberg M, Flomenblit Y, Nevo Z. A newintratracheal stent made from nitinol, an alloy with ‘shape memoryeffect’. J Thorac Cardiovasc Surg 1994;107:1255–1261.

w8x Lemaire A, Burfeind WR, Toloza E, Balderson S, Petersen RP, HarpoleDH Jr, D’Amico TA. Outcomes of tracheobronchial stents in patientswith malignant airway disease. Ann Thorac Surg 2005;80:434–437;discussion 437–438.

w9x Sutedja G, Schramel F, van Kralingen K, Postmus PE. Stent placementis justifiable in end-stage patients with malignant airway tumours.Respiration 1995;62:148–150.

w10x Tojo T, Iioka S, Kitamura S, Maeda M, Otsuji H, Uchida H, Mori T, FuruseK. Management of malignant tracheobronchial stenosis with metalstents and Dumon stents. Ann Thorac Surg 1996;61:1074–1078.

w11x Monnier P, Mudry A, Stanzel F, Haeussinger K, Heitz M, Probst R, BolligerCT. The use of the covered Wallstent for the palliative treatment ofinoperable tracheobronchial cancers. A prospective, multicenter study.Chest 1996;110:1161–1168.

w12x Wood DE. Management of malignant tracheobronchial obstruction. SurgClin North Am 2002;82:621–642.

w13x Wood DE. Airway stenting. Chest Surg Clin N Am 2001;11:841–860.w14x Wood DE, Liu YH, Vallieres E, Karmy-Jones R, Mulligan MS. Airway

stenting for malignant and benign tracheobronchial stenosis. Ann ThoracSurg 2003;76:167–172; discussion 173–164.

w15x Azzoli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J, Johnson DH,Laskin JL, Masters G, Milton D, Nordquist L, Pfister DG, Piantadosi S,Schiller JH, Smith R, Smith TJ, Strawn JR, Trent D, Giaccone G.American Society of Clinical Oncology Clinical Practice Guideline updateon chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol2009;27:6251–6266.