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Bronchoscopic palliation to treat endobronchial metastasis of the tracheobronchial tree
respiratory investigation 54 (2016) 116 –120
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Original article
Bronchoscopic palliation to treat endobronchial metastasis of the tracheobronchial tree Levent Dalar, M.D.a,n, Cengiz O¨zdemir, M.D.b, Sinem Nedime So¨ku¨cu¨, M.D.b, Levent Karasulu , M.D.b, Sedat Altın, M.D.b a Istanbul Bilim University, School of Medicine, Department of Pulmonary Medicine, Sisli Florence Nightingale Hospital, Abidei Hurriyet cd. 166, Sisli, Istanbul, Turkey b Yedikule Teaching Hospital for Pulmonology and Thoracic Surgery, Istasyon Yolu cad, Zeytinburnu, Istanbul, Turkey
ar t ic l e in f o
abs tra ct
Article history:
Background: Endobronchial metastases (EBM) are rarely observed, but they are caused by a
Received 8 May 2015
number of different tumors. Bronchoscopy is the main approach for both differential
Received in revised form
diagnosis and to maintain endoluminal palliation. In this study, consecutive EBM cases
26 August 2015
that had been diagnosed and treated were evaluated in a retrospective cohort.
Accepted 6 September 2015
Methods: In total, 18 pathologically verified patients with EBM originating from extrathor-
Available online 20 November 2015
acic tumors who were referred to our interventional pulmonology unit with respiratory
Keywords:
symptoms were retrospectively evaluated. Tumor type, metastasis location, treatment
Endobronchial metastases
method and frequency, and complications were evaluated.
Interventional bronchoscopy
Results: In total, there were 18 patients (13 women) with EBM enrolled in this study. All
Survival
were diagnosed by a bronchial biopsy. The mean age of the patients was 48715.24 years
Stent
(range: 24–76 years). The most frequent sites of origin of the metastases were the bone (5) and kidney. Obstructions were observed in the tracheas of 12 patients, in the right main bronchi of 10, and in the left main bronchi of 11. Twelve airway stents were placed in nine patients. The removal of the obstruction was effective in the remaining patients. The mean number of treatment applications was 1.47 (range: 1–3). Hemorrhage, mucostasis, and granulation were observed. The median follow-up duration was 528 days (range: 62–1177 days). The median survival time for the patients who died was 122 days (range: 2– 885 days). Conclusions: EBM is rare, and bronchoscopy is the primary method of diagnosis, followed by palliation, if necessary. & 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
n Correspondence to: Sisli Florence Nightingale Hospital, Department of Pulmonary Medicine, School of Medicine, Istanbul Bilim University, 34371 Istanbul, Turkey. Tel: þ90 5052607170; fax: þ90 2122403132. E-mail addresses: [email protected] (L. Dalar) [email protected] (C. Özdemir) [email protected] (S.N. Sökücü), [email protected] (L. Karasulu) [email protected] (S. Altın).
http://dx.doi.org/10.1016/j.resinv.2015.09.001 2212-5345/& 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
117
respiratory investigation 54 (2016) 116 –120
1.
Introduction
Pulmonary metastases are common in tumors with a high level of systemic venous drainage. Most endobronchial lesions develop secondary to primary lung malignancies. The incidence rate of endobronchial metastases (EBM) from extrapulmonary malignant tumors varies in the published literature [1,2]. The type of EBM originating from extrathoracic malignancies depends on the prevalence of the primary tumor, the histopathology of the tumor, and the stage of the tumor at presentation. Although EBMs develop because of different causes, they manifest similar symptoms, including cough, dyspnea, sputum, and hemoptysis. Diagnosis is simple when an airway obstruction has developed at the location of the lesion, and respiratory symptoms are evaluated together with radiological and bronchoscopic findings. Because EBMs are rare, most studies are retrospective in design or are case reports. In this study, we evaluated patients who were consecutively admitted over a 9-year period to our interventional bronchoscopy unit with EBM caused by primary tumors. We treated them with interventional methods, including bronchoscopy. Bronchoscopic palliation can increase survival independent of systemic and radiation therapy when applied in the early stages of the disease. We aimed to emphasize the importance of the management of this rare clinical situation by using bronchoscopic methods.
2.
Patients and methods
From January 2005 to January 2013, 943 consecutive patients who underwent rigid bronchoscopy under general anesthesia in our unit were evaluated. Of these, 18 cases with an endobronchial lesion caused by EBM were diagnosed and evaluated. These patients were all symptomatic due to central airway obstruction with a primary extrathoracic tumor. Airway obstruction was detected in these patients by computed thorax tomography and fiberoptic bronchoscopy. These patients were followed and referred to our interventional bronchology unit. Baseline characteristics, clinical symptoms, pre-treatment, radiological findings, applied methods, complications, and survival characteristics were evaluated retrospectively from the patients’ medical records. Institutional Review Board approval (IRB: 0023051212-061212-0023) was obtained to allow the use of retrospective data from the medical records. Histopathological diagnosis was confirmed in all cases by biopsy. Primary lung cancer, lymphoma, and esophageal cancer cases were excluded because these cancers can invade the tracheobronchial tree directly. All of the patients were evaluated by chest X-ray before and after the procedure. Each patient underwent a rigid bronchoscopy under general anesthesia for treatment in the Interventional Pulmonology Unit. All of the patients, except one, were hospitalized after the procedure. The patient who was not hospitalized was treated as an outpatient. Dumon (Novatech, Paris, France) stents were inserted using the appropriate equipment.
A diode laser, operating at a wavelength of 980 nm and using 4–25 W in pulsed mode (Biolitec, Ceralas D 25; Jena, Germany), was used for the endobronchial treatment. Argon plasma coagulation (40 W, blended mode-continuous flow) was applied using an instrument manufactured by ERBE Elektromedizine GmbH (Tübingen, Germany). Standardized protocols for selecting the appropriate power were used in accordance with the manufacturer’s recommendations. Cryotherapy was performed using the ERBOKRYO system (Elektromedizine GmbH). All patients were intubated by a rigid bronchoscope (Efer Endoscopy, Paris, France) under general anesthesia using standardized techniques, and mechanical debridement was applied when necessary. All patients had symptomatic relief after endobronchial treatment and stenting.
3.
Results
Among the 943 consecutive patients who underwent rigid bronchoscopy under general anesthesia in our unit, 18 (1.9%) had EDM. All patients had respiratory symptoms, including dyspnea, cough, or hemoptysis. The 18 patients included 5 (27.8%) men and 13 (72.2%) women. The mean age of the patients was 48715.24 years (range: 24–76 years). The most sites of primary tumors were bone (n¼ 5, 27.7%) and kidney (n¼ 4, 22.2%); others were soft tissue (n¼ 3, 16.7%), breast (n¼ 2, 11.1%), and one case each of malignant melanoma, nasopharynx, cervix, and testis (Table 1). A representative image from one patient with chondrosarcoma who underwent bronchoscopic removal is shown in Fig. 1. Obstructions were observed in the trachea in 12 patients, in the right main bronchus in 10 patients, in the left main bronchus in 11 patients, and in the left upper lobe entrance in 1 patient. Mechanical dilatation was performed during every session. The obstruction was removed using a hot mechanical device (a diode laser or argon plasma coagulation). If bleeding occurred after the removal of the obstruction, the hot device was used to control the bleeding. The hot device was used on the base of the tumor to delay recurrence or to eradicate the tumor. Once the endoscopic debulking was complete, the patient was considered for stent insertion. Stents were inserted when bulging extrinsic compression was present or the luminal compromise was greater than 50%. In total, 12 stents were Table 1 – Demographic characteristics of the cases and origins of the primary tumors (n¼ 18). Demographical data of the patients
n
Gender (male/female) (%) Age (y) Bone (n) (%) Kidney (n) (%) Soft tissue (n) (%) Breast (n) (%) Malignant melanoma (n) (%) Nasopharynx (n) (%) Cervix (n) (%) Testis (n) (%)
5/13, (27.8%/72.2%) 48715.24 (range: 24–76) 5 (27.7%) 4 (22.2%) 3 (16.7%) 2 (11.1%) 1 (5.6%) 1 (5.6%) 1 (5.6%) 1 (5.6%)
118
respiratory investigation 54 (2016) 116 –120
Fig. 1 – A 53-year-old female patient presented with opacity of the left lung. (A) An endobronchial metastatic lesion caused by chondrosarcoma was present at the entrance of the left main bronchus. (B) After diode laser application and excision of the lesion by mechanical debridement, the patency of the left main bronchus was maintained. (C) The large tumor was removed by rigid bronchoscopy. Table 2 – Bronchoscopic methods and properties of the stents used for palliation of the endobronchial metastases. Interventions and related parameters
Patients (n)
Location of EBM Trachea RMB LMB Multiple
6 2 2 8
Intervention and treatment modality FOB Rigid Core-out APC Diode laser Cryotherapy
17 28 17 11 6 1
Type of stent Silicone Y stent Straight silicone stent SEMS
4 4 1
Location of stent Carina RMB LMB Trachea
4 0 2 3
Complications Hemorrhage Desaturation Bradycardia Granulation Mucostasis Stent migration
3 1 1 3 2 0
and a stent was not required. In total, 27 bronchoscopies were performed in the 18 cases. The bronchoscopic methods and properties of the stents are summarized in Table 2. The mean number of applications was 1.47 per patient (range: 1–3). One bronchoscopy session was sufficient to recreate an optimal airway in 10 patients. More than one therapeutic session was needed in 44.4% of patients. Hemorrhage occurred as a result of the procedure in three cases, but the bleeding was minor and did not cause mortality. Other than hemorrhage, moderate mucostasis on the left side and moderate tracheal mucostasis were observed in one patient each; both were easily cleared in the follow-up fiberoptic bronchoscopy. Stent migration was not observed in any patient. In six cases, granulated tissue ingrowths were observed at the distal end of the stent. Five of the patients were alive after a median follow-up time of 528 days (range: 62– 1177 days). The median survival for the patients who died was 122 days (range: 2–885 days) (Fig. 2).
4.
Abbreviations: EBM, Endobronchial metastasis; RMB, right main bronchus; LMB, left main bronchus; APC, argon plasma coagulation; FOB, fiberoptic bronchoscopy; SEMS, self-expandable metallic stent.
applied to nine patients after dilatation of the airway, including four patients who received Y stents, three who received tracheal stents, one who received a left main bronchus stent, and one patient who received two tracheal stents. In the remaining patients, the removal of the obstruction using the thermal method created an optimal airway,
Discussion
Endobronchial metastases of extrathoracic tumors are very rare, ranging from 2% to 28% of cases depending on how they are defined. EBM causes symptoms mimicking lung malignancies [1,2] and can mimic a primary bronchogenic carcinoma. The symptoms and radiological findings of EBM are indistinguishable from those of primary lung cancer, and the bronchoscopic findings are also similar; therefore, pathological differentiation from primary lung cancer is important before definitive therapy [3]. Of all bronchoscopic examinations performed over an 18year period for malignancies in one center, 5.6 cases per year showed EBM with a statistically significant increase in the last 8 years. The center detected that 4% of endobronchial biopsies for suspected malignancy revealed an EBM from an extrapulmonary tumor [4]. In another center, there were a total of 18 cases of EBM from among 1275 patients who had undergone diagnostic bronchoscopic procedures over a 10year period, resulting in an incidence of 1.4% [5]. These rates support the rarity of the condition. In our center, EBM accounts for 1.9% of cases, but it is difficult to determine the actual frequency of these tumors because our center is a
respiratory investigation 54 (2016) 116 –120
Fig. 2 – Graph of the cumulative survival of the patients. Although most of the patients died in the early post intervention follow-up, a small number of survivors survived long after the interventional bronchoscopy. referral clinic for interventional pulmonology, and only patients who had undergone an intervention at our clinic were evaluated. Breast (30%), colorectal (24%), renal (14%), gastric (6%), and prostate (4.5%) cancers and melanoma (4.5%) were the most common metastatic neoplasms presenting as an endobronchial mass [4]. The most common primary malignancies were colorectal and breast cancer (four cases of each), followed by cervical cancer (three cases) and renal cell carcinoma (two cases) [5]. In another series from our country, the primary tumor sites were colorectal (four cases), breast (three cases), renal (three cases), lymphoma (three cases), rhabdomyosarcoma (two cases), bladder (one case), thyroid (one case) and malignant melanoma (one case) [6]. In our series, the most common primary tissues were bone (n¼5, 27.7%) and kidney (n¼4, 22.2%); others were soft tissue (n¼ 3, 16.7%), breast (n¼2, 11.1%), and one case each of malignant melanoma, nasopharynx, cervix, and testicular tumors. Owing to the low incidence of EBM and the particular characteristics of each center, results vary from study to study. The location of the EBM in the bronchial tree may also vary. In one series, the EBM was located in the right bronchial tree in 56–80% of cases [7–11]. However, our series showed that the trachea and the right and left main bronchus were all equally involved. Although some reviews have mentioned that these tumors can be asymptomatic, all of our patients presented with respiratory symptoms [4,9,12]. This could be because we are working in an interventional pulmonology clinic, and only patients with obvious symptoms are referred. A malignant central airway obstruction can be a problem in extrathoracic malignancies. A symptomatic obstruction can often be treated successfully using endoscopy. Endobronchial methods are used to treat the primary disease in the management of EBM tumors. In a much earlier study by Cavaliere et al., interventional bronchoscopy performed prior to radio- or chemo-therapy appeared to be a better treatment option and also improved the tolerance to radiotherapy and decreased the risk of bronchial stenosis or radiotherapy-induced pneumonitis [13]. The goal of treating exophytic obstructions is to remove the endobronchial tumor
119
growth. Depending on the indication to achieve immediate relief, we used the following techniques in our series: mechanical debulking and core out, dilatation and argon plasma coagulation, and laser resection. Mechanical debulking, electrocautery/diathermy, argon plasma coagulation, laser resection, and cryoextraction can be used to provide immediate relief, while cryotherapy, brachytherapy, and photodynamic therapy can be used for delayed effects [14]. More than one therapeutic session may be needed, and interventional bronchoscopy has the great advantage that it can be repeated, if necessary, whereas radiotherapy and brachytherapy are not recommended to be repeated in regions that have already been treated. In a colorectal cancer series reported by Fournel et al., more than one therapeutic session was needed in 41% of subjects owing to the recurrent nature of EBM. As in our series, more than one session was needed in 44.4% of the patients with a mean number of applications of 1.47 (range: 1–3). Silicone or self-expanding metallic airway stents can be used for the treatment of airway obstruction due to extrinsic disease to restore and maintain airway patency [15]. In a colorectal carcinoma series, few stents were inserted owing to the low rate of external compression [16]. In our series, we used 12 stents in nine patients depending on the bronchoscopic findings to maintain the immediate relief obtained by interventional techniques. Although silicone stents are the most commonly placed stents in malignant airways, metallic stents show improved outcomes under selected conditions [17]. In our series, all of the stents were silicon stents. A stent was used if the airway lumen was narrowed by more than 50% because of enlarged mediastinal lymph nodes and/or submucosal infiltration after appropriate removal of the obstruction; if the airway lumen opening was greater than 50%, a stent was used to prevent closing of the airway due to fast ingrowth of the tumor by the barrier effect. Although it depends on the tumor type, survival after EBM diagnosis is generally poor. In the literature, the survival of patients after the diagnosis of EBM is between 12 and 15 months, as it is a manifestation that appears in advanced stages of the disease [4,18,19]. However, longer survival times in patients with EBM originating from thyroid, breast, or rectal cancers have been reported [5,20]. The median survival time in a series of 18 patients published by Sang Hong Lee et al. after the diagnosis of EBM was 10 months (range: 1–39 months) [5]. In their series, the type of endobronchial treatment was not documented. The mean survival time after an EBM diagnosis in long-term survivors was also affected by the treatment received. Patients who received treatment survived longer compared to those with supportive care (17.4 months vs. 12.4 months, respectively) [5]. Moreover, respiratory symptoms of EBM may be treated by various safe procedures, and in some cases, intrabronchial therapy may prolong patient survival [16,20]. In our series, the mean survival time was 122 days (range: 2–885 days). This could be explained by the late referral of these patients to our center with severe respiratory distress symptoms. Additionally, survival depends on the biological behavior of the primary tumor and its responsiveness to the primary therapy. In this aspect, endobronchial treatment is only an adjunct to the primary treatment of the tumor that can be used to increase the survival time. Removal of the obstruction by maintaining a safe airway
120
respiratory investigation 54 (2016) 116 –120
opening can be effective for longer survival. EBM is a clinical situation that is ignored in the early stages of the primary tumor follow-up. Detection of respiratory findings on physical examination, such as recurrent pneumonia and new or increased dyspnea, should be evaluated to assess whether they are caused by an obstruction, and early therapeutic bronchoscopic methods should be considered. The complication rates of the applications were the same as those for other malignant airway obstruction cases [15]. In our series, hemorrhage, mucostasis, and granulated tissue were observed as a result of the procedure, but stent migration was not seen. None of the complications was difficult to manage, and the procedure did not result in mortality. Our study had some obvious limitations, including the use of a retrospective cohort analysis with no control group. Additionally, not taking other parameters related to the tumor into consideration is problematic with respect to the survival analysis. As a result, we can only discuss the survival benefit for patients whose endobronchial obstruction was relieved after suspicion of EBM of the primary tumor. However, it is clear that bronchoscopy has limited value for addressing the respiratory distress of patients who have exhausted all other treatment options. Even so, prospective, large cohort studies are needed to evaluate this situation. Another important limitation of the study is that the effective performance scale for bronchoscopic palliation was not shown by comparison of the respiratory function test, dyspnea scale, radiological findings, and arterial blood gas analysis.
5.
Conclusion
In conclusion, the possibility of central airway metastasis should always be considered if patients with a history of malignancy present with symptoms of respiratory distress or recurrent chest infections. There are still no data on the increase in survival associated with interventional bronchoscopic approaches. It is known that the use of these applications increases the quality of life in patients with EBM. Additionally, relief of symptoms and prevention of asphyxia provides time for other treatment options in the management of these patients. Initial treatment by interventional endoscopy could be life-saving in some cases and can be repeated if needed. More prospective studies need to be performed to confirm that this is a safe and effective method that may improve the quality of life in patients with EBM. This palliative measure requires a combined approach involving oncologists and bronchoscopists, and these patients should be referred to bronchoscopists when suspicion exists. Finally, management should be individualized for each patient.
Conflict of interest The authors have no conflicts of interest.
Acknowledgments None.
r e f e r e n c e s
[1] Rosenblatt MB, Lisa JR, Trinidad S. Pitfalls in the clinical histologic diagnosis of bronchogenic carcinoma. Dis Chest 1966;49:396–404. [2] Braman SS, Whitcomb ME. Endobronchial metastasis. Arch Intern Med 1975;135:543–7. [3] Katsimbri PP, Bamias AT, Froudarakis ME, et al. Endobronchial metastases secondary to solid tumors: report of eight cases and review of the literature. Lung Cancer 2000;28:163–70. [4] Marchioni A, Lasagni A, Busca A, et al. Endobronchial metastasis: an epidemiologic and clinicopathologic study of 174 consecutive cases. Lung Cancer 2014;84:222–8. [5] Lee SH, Jung JY, Kim Do H, et al. Endobronchial metastases from extrathoracic malignancy. Yonsei Med J 2013;54:403–9. [6] Dursun AB, Demirag F, Bayiz H, et al. Endobronchial metastases: a clinicopathological analysis. Respirology 2005;10:510–4. [7] Heitmiller RF, Marasco WJ, Hruban RH, et al. Endobronchial metastasis. J Thorac Cardiovasc Surg 1993;106:537–42. [8] Salud A, Porcel JM, Rovirosa A, Bellmunt J. Endobronchial metastatic disease: analysis of 32 cases. J Surg Oncol 1996;62:249–52. [9] Kiryu T, Hoshi H, Matsui E, et al. Endotracheal/endobronchial metastases: clinicopathologic study with special reference to developmental modes. Chest 2001;119:768–75. [10] Kim JH, Min D, Song SH, et al. Endobronchial metastases from extrathoracic malignancies: recent 10 years’ experience in a single university hospital. Tuberc Respir Dis (Seoul) 2013;74:169–76. [11] Akoglu S, Uc¸an ES, Celik G, et al. Endobronchial metastases from extrathoracic malignancies. Clin Exp Metastasis 2005;22:587–91. [12] Li J, Xu BH, Wang JY, et al. Endobronchial metastases from breast cancer: a clinicopathological and survival analysis. Zhonghua Zhong Liu Za Zhi 2012;34:394–7. [13] Cavaliere S, Venuta F, Foccoli P, et al. Endoscopic treatment of malignant airway obstruction in 2008 patients. Chest 1996;110:1536–42. [14] Hetzel J, Bo¨ckeler M. Endoscopic treatment for tumorous obstructions of the tracheobronchial system: a comparison of available techniques. Pneumologie 2012;66:408–15, . http: //dx.doi.org/10.1055/s-0031-1291647. [15] Wahidi MM, Herth FJ, Ernst A. State of the art: interventional pulmonology. Chest 2007;131:261–74. [16] Fournel C, Bertoletti L, Nguyen B, et al. Endobronchial metastases from colorectal cancers: natural history and role of interventional bronchoscopy. Respiration 2009;77:63–9, . http://dx.doi.org/10.1159/000158487. [17] Dutau H, Musani AI, Plojoux J, et al. The use of selfexpandable metallic stents in the airways in the adult population. Expert Rev Respir Med 2014;8:179–90 doi: 0.1586/ 17476348.2014.880055. [18] Lee YC, Wong CS, Jeffery GM. Endobronchial metastasis from rectal adenocarcinoma. Respir Med 1997;91:245–8. [19] Heitmiller RF, Marasco WJ, Hruban RH, et al. Endobronchial metastasis. J Thorac Cardiovasc Surg 1993;106:537–42. [20] Carlin BW, Harrell 2nd JH, Olson LK, et al. Endobronchial metastases due to colorectal carcinoma. Chest 1989;96:1110–4.
Contents lists available at ScienceDirect
Respiratory Investigation journal homepage: www.elsevier.com/locate/resinv
Original article
Bronchoscopic palliation to treat endobronchial metastasis of the tracheobronchial tree Levent Dalar, M.D.a,n, Cengiz O¨zdemir, M.D.b, Sinem Nedime So¨ku¨cu¨, M.D.b, Levent Karasulu , M.D.b, Sedat Altın, M.D.b a Istanbul Bilim University, School of Medicine, Department of Pulmonary Medicine, Sisli Florence Nightingale Hospital, Abidei Hurriyet cd. 166, Sisli, Istanbul, Turkey b Yedikule Teaching Hospital for Pulmonology and Thoracic Surgery, Istasyon Yolu cad, Zeytinburnu, Istanbul, Turkey
ar t ic l e in f o
abs tra ct
Article history:
Background: Endobronchial metastases (EBM) are rarely observed, but they are caused by a
Received 8 May 2015
number of different tumors. Bronchoscopy is the main approach for both differential
Received in revised form
diagnosis and to maintain endoluminal palliation. In this study, consecutive EBM cases
26 August 2015
that had been diagnosed and treated were evaluated in a retrospective cohort.
Accepted 6 September 2015
Methods: In total, 18 pathologically verified patients with EBM originating from extrathor-
Available online 20 November 2015
acic tumors who were referred to our interventional pulmonology unit with respiratory
Keywords:
symptoms were retrospectively evaluated. Tumor type, metastasis location, treatment
Endobronchial metastases
method and frequency, and complications were evaluated.
Interventional bronchoscopy
Results: In total, there were 18 patients (13 women) with EBM enrolled in this study. All
Survival
were diagnosed by a bronchial biopsy. The mean age of the patients was 48715.24 years
Stent
(range: 24–76 years). The most frequent sites of origin of the metastases were the bone (5) and kidney. Obstructions were observed in the tracheas of 12 patients, in the right main bronchi of 10, and in the left main bronchi of 11. Twelve airway stents were placed in nine patients. The removal of the obstruction was effective in the remaining patients. The mean number of treatment applications was 1.47 (range: 1–3). Hemorrhage, mucostasis, and granulation were observed. The median follow-up duration was 528 days (range: 62–1177 days). The median survival time for the patients who died was 122 days (range: 2– 885 days). Conclusions: EBM is rare, and bronchoscopy is the primary method of diagnosis, followed by palliation, if necessary. & 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
n Correspondence to: Sisli Florence Nightingale Hospital, Department of Pulmonary Medicine, School of Medicine, Istanbul Bilim University, 34371 Istanbul, Turkey. Tel: þ90 5052607170; fax: þ90 2122403132. E-mail addresses: [email protected] (L. Dalar) [email protected] (C. Özdemir) [email protected] (S.N. Sökücü), [email protected] (L. Karasulu) [email protected] (S. Altın).
http://dx.doi.org/10.1016/j.resinv.2015.09.001 2212-5345/& 2015 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
117
respiratory investigation 54 (2016) 116 –120
1.
Introduction
Pulmonary metastases are common in tumors with a high level of systemic venous drainage. Most endobronchial lesions develop secondary to primary lung malignancies. The incidence rate of endobronchial metastases (EBM) from extrapulmonary malignant tumors varies in the published literature [1,2]. The type of EBM originating from extrathoracic malignancies depends on the prevalence of the primary tumor, the histopathology of the tumor, and the stage of the tumor at presentation. Although EBMs develop because of different causes, they manifest similar symptoms, including cough, dyspnea, sputum, and hemoptysis. Diagnosis is simple when an airway obstruction has developed at the location of the lesion, and respiratory symptoms are evaluated together with radiological and bronchoscopic findings. Because EBMs are rare, most studies are retrospective in design or are case reports. In this study, we evaluated patients who were consecutively admitted over a 9-year period to our interventional bronchoscopy unit with EBM caused by primary tumors. We treated them with interventional methods, including bronchoscopy. Bronchoscopic palliation can increase survival independent of systemic and radiation therapy when applied in the early stages of the disease. We aimed to emphasize the importance of the management of this rare clinical situation by using bronchoscopic methods.
2.
Patients and methods
From January 2005 to January 2013, 943 consecutive patients who underwent rigid bronchoscopy under general anesthesia in our unit were evaluated. Of these, 18 cases with an endobronchial lesion caused by EBM were diagnosed and evaluated. These patients were all symptomatic due to central airway obstruction with a primary extrathoracic tumor. Airway obstruction was detected in these patients by computed thorax tomography and fiberoptic bronchoscopy. These patients were followed and referred to our interventional bronchology unit. Baseline characteristics, clinical symptoms, pre-treatment, radiological findings, applied methods, complications, and survival characteristics were evaluated retrospectively from the patients’ medical records. Institutional Review Board approval (IRB: 0023051212-061212-0023) was obtained to allow the use of retrospective data from the medical records. Histopathological diagnosis was confirmed in all cases by biopsy. Primary lung cancer, lymphoma, and esophageal cancer cases were excluded because these cancers can invade the tracheobronchial tree directly. All of the patients were evaluated by chest X-ray before and after the procedure. Each patient underwent a rigid bronchoscopy under general anesthesia for treatment in the Interventional Pulmonology Unit. All of the patients, except one, were hospitalized after the procedure. The patient who was not hospitalized was treated as an outpatient. Dumon (Novatech, Paris, France) stents were inserted using the appropriate equipment.
A diode laser, operating at a wavelength of 980 nm and using 4–25 W in pulsed mode (Biolitec, Ceralas D 25; Jena, Germany), was used for the endobronchial treatment. Argon plasma coagulation (40 W, blended mode-continuous flow) was applied using an instrument manufactured by ERBE Elektromedizine GmbH (Tübingen, Germany). Standardized protocols for selecting the appropriate power were used in accordance with the manufacturer’s recommendations. Cryotherapy was performed using the ERBOKRYO system (Elektromedizine GmbH). All patients were intubated by a rigid bronchoscope (Efer Endoscopy, Paris, France) under general anesthesia using standardized techniques, and mechanical debridement was applied when necessary. All patients had symptomatic relief after endobronchial treatment and stenting.
3.
Results
Among the 943 consecutive patients who underwent rigid bronchoscopy under general anesthesia in our unit, 18 (1.9%) had EDM. All patients had respiratory symptoms, including dyspnea, cough, or hemoptysis. The 18 patients included 5 (27.8%) men and 13 (72.2%) women. The mean age of the patients was 48715.24 years (range: 24–76 years). The most sites of primary tumors were bone (n¼ 5, 27.7%) and kidney (n¼ 4, 22.2%); others were soft tissue (n¼ 3, 16.7%), breast (n¼ 2, 11.1%), and one case each of malignant melanoma, nasopharynx, cervix, and testis (Table 1). A representative image from one patient with chondrosarcoma who underwent bronchoscopic removal is shown in Fig. 1. Obstructions were observed in the trachea in 12 patients, in the right main bronchus in 10 patients, in the left main bronchus in 11 patients, and in the left upper lobe entrance in 1 patient. Mechanical dilatation was performed during every session. The obstruction was removed using a hot mechanical device (a diode laser or argon plasma coagulation). If bleeding occurred after the removal of the obstruction, the hot device was used to control the bleeding. The hot device was used on the base of the tumor to delay recurrence or to eradicate the tumor. Once the endoscopic debulking was complete, the patient was considered for stent insertion. Stents were inserted when bulging extrinsic compression was present or the luminal compromise was greater than 50%. In total, 12 stents were Table 1 – Demographic characteristics of the cases and origins of the primary tumors (n¼ 18). Demographical data of the patients
n
Gender (male/female) (%) Age (y) Bone (n) (%) Kidney (n) (%) Soft tissue (n) (%) Breast (n) (%) Malignant melanoma (n) (%) Nasopharynx (n) (%) Cervix (n) (%) Testis (n) (%)
5/13, (27.8%/72.2%) 48715.24 (range: 24–76) 5 (27.7%) 4 (22.2%) 3 (16.7%) 2 (11.1%) 1 (5.6%) 1 (5.6%) 1 (5.6%) 1 (5.6%)
118
respiratory investigation 54 (2016) 116 –120
Fig. 1 – A 53-year-old female patient presented with opacity of the left lung. (A) An endobronchial metastatic lesion caused by chondrosarcoma was present at the entrance of the left main bronchus. (B) After diode laser application and excision of the lesion by mechanical debridement, the patency of the left main bronchus was maintained. (C) The large tumor was removed by rigid bronchoscopy. Table 2 – Bronchoscopic methods and properties of the stents used for palliation of the endobronchial metastases. Interventions and related parameters
Patients (n)
Location of EBM Trachea RMB LMB Multiple
6 2 2 8
Intervention and treatment modality FOB Rigid Core-out APC Diode laser Cryotherapy
17 28 17 11 6 1
Type of stent Silicone Y stent Straight silicone stent SEMS
4 4 1
Location of stent Carina RMB LMB Trachea
4 0 2 3
Complications Hemorrhage Desaturation Bradycardia Granulation Mucostasis Stent migration
3 1 1 3 2 0
and a stent was not required. In total, 27 bronchoscopies were performed in the 18 cases. The bronchoscopic methods and properties of the stents are summarized in Table 2. The mean number of applications was 1.47 per patient (range: 1–3). One bronchoscopy session was sufficient to recreate an optimal airway in 10 patients. More than one therapeutic session was needed in 44.4% of patients. Hemorrhage occurred as a result of the procedure in three cases, but the bleeding was minor and did not cause mortality. Other than hemorrhage, moderate mucostasis on the left side and moderate tracheal mucostasis were observed in one patient each; both were easily cleared in the follow-up fiberoptic bronchoscopy. Stent migration was not observed in any patient. In six cases, granulated tissue ingrowths were observed at the distal end of the stent. Five of the patients were alive after a median follow-up time of 528 days (range: 62– 1177 days). The median survival for the patients who died was 122 days (range: 2–885 days) (Fig. 2).
4.
Abbreviations: EBM, Endobronchial metastasis; RMB, right main bronchus; LMB, left main bronchus; APC, argon plasma coagulation; FOB, fiberoptic bronchoscopy; SEMS, self-expandable metallic stent.
applied to nine patients after dilatation of the airway, including four patients who received Y stents, three who received tracheal stents, one who received a left main bronchus stent, and one patient who received two tracheal stents. In the remaining patients, the removal of the obstruction using the thermal method created an optimal airway,
Discussion
Endobronchial metastases of extrathoracic tumors are very rare, ranging from 2% to 28% of cases depending on how they are defined. EBM causes symptoms mimicking lung malignancies [1,2] and can mimic a primary bronchogenic carcinoma. The symptoms and radiological findings of EBM are indistinguishable from those of primary lung cancer, and the bronchoscopic findings are also similar; therefore, pathological differentiation from primary lung cancer is important before definitive therapy [3]. Of all bronchoscopic examinations performed over an 18year period for malignancies in one center, 5.6 cases per year showed EBM with a statistically significant increase in the last 8 years. The center detected that 4% of endobronchial biopsies for suspected malignancy revealed an EBM from an extrapulmonary tumor [4]. In another center, there were a total of 18 cases of EBM from among 1275 patients who had undergone diagnostic bronchoscopic procedures over a 10year period, resulting in an incidence of 1.4% [5]. These rates support the rarity of the condition. In our center, EBM accounts for 1.9% of cases, but it is difficult to determine the actual frequency of these tumors because our center is a
respiratory investigation 54 (2016) 116 –120
Fig. 2 – Graph of the cumulative survival of the patients. Although most of the patients died in the early post intervention follow-up, a small number of survivors survived long after the interventional bronchoscopy. referral clinic for interventional pulmonology, and only patients who had undergone an intervention at our clinic were evaluated. Breast (30%), colorectal (24%), renal (14%), gastric (6%), and prostate (4.5%) cancers and melanoma (4.5%) were the most common metastatic neoplasms presenting as an endobronchial mass [4]. The most common primary malignancies were colorectal and breast cancer (four cases of each), followed by cervical cancer (three cases) and renal cell carcinoma (two cases) [5]. In another series from our country, the primary tumor sites were colorectal (four cases), breast (three cases), renal (three cases), lymphoma (three cases), rhabdomyosarcoma (two cases), bladder (one case), thyroid (one case) and malignant melanoma (one case) [6]. In our series, the most common primary tissues were bone (n¼5, 27.7%) and kidney (n¼4, 22.2%); others were soft tissue (n¼ 3, 16.7%), breast (n¼2, 11.1%), and one case each of malignant melanoma, nasopharynx, cervix, and testicular tumors. Owing to the low incidence of EBM and the particular characteristics of each center, results vary from study to study. The location of the EBM in the bronchial tree may also vary. In one series, the EBM was located in the right bronchial tree in 56–80% of cases [7–11]. However, our series showed that the trachea and the right and left main bronchus were all equally involved. Although some reviews have mentioned that these tumors can be asymptomatic, all of our patients presented with respiratory symptoms [4,9,12]. This could be because we are working in an interventional pulmonology clinic, and only patients with obvious symptoms are referred. A malignant central airway obstruction can be a problem in extrathoracic malignancies. A symptomatic obstruction can often be treated successfully using endoscopy. Endobronchial methods are used to treat the primary disease in the management of EBM tumors. In a much earlier study by Cavaliere et al., interventional bronchoscopy performed prior to radio- or chemo-therapy appeared to be a better treatment option and also improved the tolerance to radiotherapy and decreased the risk of bronchial stenosis or radiotherapy-induced pneumonitis [13]. The goal of treating exophytic obstructions is to remove the endobronchial tumor
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growth. Depending on the indication to achieve immediate relief, we used the following techniques in our series: mechanical debulking and core out, dilatation and argon plasma coagulation, and laser resection. Mechanical debulking, electrocautery/diathermy, argon plasma coagulation, laser resection, and cryoextraction can be used to provide immediate relief, while cryotherapy, brachytherapy, and photodynamic therapy can be used for delayed effects [14]. More than one therapeutic session may be needed, and interventional bronchoscopy has the great advantage that it can be repeated, if necessary, whereas radiotherapy and brachytherapy are not recommended to be repeated in regions that have already been treated. In a colorectal cancer series reported by Fournel et al., more than one therapeutic session was needed in 41% of subjects owing to the recurrent nature of EBM. As in our series, more than one session was needed in 44.4% of the patients with a mean number of applications of 1.47 (range: 1–3). Silicone or self-expanding metallic airway stents can be used for the treatment of airway obstruction due to extrinsic disease to restore and maintain airway patency [15]. In a colorectal carcinoma series, few stents were inserted owing to the low rate of external compression [16]. In our series, we used 12 stents in nine patients depending on the bronchoscopic findings to maintain the immediate relief obtained by interventional techniques. Although silicone stents are the most commonly placed stents in malignant airways, metallic stents show improved outcomes under selected conditions [17]. In our series, all of the stents were silicon stents. A stent was used if the airway lumen was narrowed by more than 50% because of enlarged mediastinal lymph nodes and/or submucosal infiltration after appropriate removal of the obstruction; if the airway lumen opening was greater than 50%, a stent was used to prevent closing of the airway due to fast ingrowth of the tumor by the barrier effect. Although it depends on the tumor type, survival after EBM diagnosis is generally poor. In the literature, the survival of patients after the diagnosis of EBM is between 12 and 15 months, as it is a manifestation that appears in advanced stages of the disease [4,18,19]. However, longer survival times in patients with EBM originating from thyroid, breast, or rectal cancers have been reported [5,20]. The median survival time in a series of 18 patients published by Sang Hong Lee et al. after the diagnosis of EBM was 10 months (range: 1–39 months) [5]. In their series, the type of endobronchial treatment was not documented. The mean survival time after an EBM diagnosis in long-term survivors was also affected by the treatment received. Patients who received treatment survived longer compared to those with supportive care (17.4 months vs. 12.4 months, respectively) [5]. Moreover, respiratory symptoms of EBM may be treated by various safe procedures, and in some cases, intrabronchial therapy may prolong patient survival [16,20]. In our series, the mean survival time was 122 days (range: 2–885 days). This could be explained by the late referral of these patients to our center with severe respiratory distress symptoms. Additionally, survival depends on the biological behavior of the primary tumor and its responsiveness to the primary therapy. In this aspect, endobronchial treatment is only an adjunct to the primary treatment of the tumor that can be used to increase the survival time. Removal of the obstruction by maintaining a safe airway
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opening can be effective for longer survival. EBM is a clinical situation that is ignored in the early stages of the primary tumor follow-up. Detection of respiratory findings on physical examination, such as recurrent pneumonia and new or increased dyspnea, should be evaluated to assess whether they are caused by an obstruction, and early therapeutic bronchoscopic methods should be considered. The complication rates of the applications were the same as those for other malignant airway obstruction cases [15]. In our series, hemorrhage, mucostasis, and granulated tissue were observed as a result of the procedure, but stent migration was not seen. None of the complications was difficult to manage, and the procedure did not result in mortality. Our study had some obvious limitations, including the use of a retrospective cohort analysis with no control group. Additionally, not taking other parameters related to the tumor into consideration is problematic with respect to the survival analysis. As a result, we can only discuss the survival benefit for patients whose endobronchial obstruction was relieved after suspicion of EBM of the primary tumor. However, it is clear that bronchoscopy has limited value for addressing the respiratory distress of patients who have exhausted all other treatment options. Even so, prospective, large cohort studies are needed to evaluate this situation. Another important limitation of the study is that the effective performance scale for bronchoscopic palliation was not shown by comparison of the respiratory function test, dyspnea scale, radiological findings, and arterial blood gas analysis.
5.
Conclusion
In conclusion, the possibility of central airway metastasis should always be considered if patients with a history of malignancy present with symptoms of respiratory distress or recurrent chest infections. There are still no data on the increase in survival associated with interventional bronchoscopic approaches. It is known that the use of these applications increases the quality of life in patients with EBM. Additionally, relief of symptoms and prevention of asphyxia provides time for other treatment options in the management of these patients. Initial treatment by interventional endoscopy could be life-saving in some cases and can be repeated if needed. More prospective studies need to be performed to confirm that this is a safe and effective method that may improve the quality of life in patients with EBM. This palliative measure requires a combined approach involving oncologists and bronchoscopists, and these patients should be referred to bronchoscopists when suspicion exists. Finally, management should be individualized for each patient.
Conflict of interest The authors have no conflicts of interest.
Acknowledgments None.
r e f e r e n c e s
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