Seminars in Thoracic and Cardiovascular Surgery Volume 21, Issue 3, Autumn 2009, Pages 290-295 Contemporary Issues in Coronary Bypass Surgery Edited by John G. Byrne, MD; Airway Surgery: Evaluation, Surgery and Treatment Edited by Cameron D. Wright, MD
doi:10.1053/j.semtcvs.2009.06.001 | How to Cite or Link Using DOI Copyright © 2009 Elsevier Inc. All rights reserved. Permissions & Reprints Airway surgery: Evaluation, surgery and treatment Treatment of Tracheal Tumors Henning A. Gaissert MD ,
,
, Jimmie Honings MD and Manjusha Gokhale MA†
†Boston University School of Public Health, Boston, Massachusetts Division of Thoracic Surgery, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, Massachusetts
Available online 25 November 2009.
The evidence for the treatment of tracheal tumors rests on a small number of single-institution series, national surveys, and epidemiologic studies. From this evidence, the following observations have been made: tracheal tumors are rare and must be identified among a much larger number of metastatic malignant tracheal lesions; most tracheal tumors are malignant; most tracheal tumors in selected series are resectable; and survival after resection exceeds survival after nonoperative treatment, even if resection margins are close. A discussion of evaluation and treatment of these tumors in this review proceeds along a systematic series of questions. Keywords: adenoid cystic carcinoma; bronchoscopy; radiation; squamous cell carcinoma; trachea; tracheal resection; tracheal tumors Article Outline Is the Observed Tracheal Mass a Primary Tumor? Is the Tumor Benign or Malignant?
What Therapy Should Be Selected? What Is the Role of Neoadjuvant Therapy? What Are the Indications for Insertion of a Tracheal Stent? Does Segmental Resection for Tracheal Tumors Conform to Oncological Principles? When Is Resection Not Indicated? What Length of Resection Is Safe? Which Factors Increase the Risk of Operative Complications? Should Mediastinal Lymph Node Dissection Be Part of the Resection? Which Patients Require Postoperative Adjuvant Therapy? What Follow-Up Is Recommended After Resection? References Evidence guiding the treatment of tracheal tumors was gained from single-institution reports and a few epidemiologic studies. In this review, we attempt to present this evidence along a series of clinical questions potentially posed by the practicing thoracic surgeon attending to a patient with neoplastic tracheal disease. The techniques of tracheal resection have been refined and popularized in the past several decades and many more surgeons possess the requisite technical skills to treat these tumors. The epidemiologic evidence, however, suggests that surgical therapy remains underutilized.[1], [2] and [3] Clinical reviews can neither reverse this situation nor replace the personal judgment of the experienced surgeon, of which there are few. They may, however, raise awareness of the disease and its initial evaluation. The thoracic surgeon without tracheal expertise must recognize independently those tumors amenable to low-risk tracheal resection and separate them from more extensive lesions that are best referred to the tracheal surgeon specialist. Our questions are meant to guide the reader through the process of arriving at these decisions. Is the Observed Tracheal Mass a Primary Tumor? Malignant tracheal obstruction occurs frequently, whereas tracheal tumors are rare. Lung or laryngeal cancer, mediastinal lymphoma, and even esophageal cancer are common thoracic malignancies, and their metastatic peritracheal lymph nodes often erode the tracheal lumen. The difference in incidence to primary tumors is striking; according to some estimates, primary tumors of the trachea are less frequent by a factor of 1000.4 The surgeon evaluating a tracheal mass may therefore assume a metastatic malignancy unless additional findings point to primary disease. In addition to the careful interpretation of radiographic studies, certain criteria suggest the presence of a primary tumor: absence of lung masses except those consistent with pulmonary metastases of tracheal carcinoma, absence of extensive mediastinal or hilar lymph node enlargement, and absence of distant metastasis. The challenge consists of finding the few candidates for resection among the many who are not.
Is the Tumor Benign or Malignant? Even when the 2 most common tracheal cancers, squamous cell and adenoid cystic carcinoma, are excluded, an overwhelming majority of remaining tumors are malignant. These consist of diverse lesions, among them mucoepidermoid carcinoma, nonsquamous carcinoma, sarcoma, and carcinoid tumors. Table 1 shows the marked imbalance toward malignant lesions encountered by 1 thoracic surgical unit. The expectation of malignant primary neoplasms informs the selection of therapy. Because less than 10% of tumors in a single-institution series were benign,5 one may conclude that subtotal removal by endobronchial techniques does not constitute adequate treatment for a tracheal tumor because complete resection cannot be confirmed. Table 1. The Spectrum of Tracheal Tumors Encountered in 357 Patients Over More Than 40 Years at MGH No. of Patients Malignant Lesions Adenoid cystic carcinoma
135
Squamous cell carcinoma
135
Carcinoids Typical
10
Atypical
1
Lymphoma
2
Melanoma
1
Mucoepidermoid carcinoma
14
Nonsquamous carcinoma
15
Small cell carcinoma
5
Adenocarcinoma
4
Large cell carcinoma
4
Adenosquamous carcinoma
2
Sarcoma
13
Spindle cell sarcoma
6
No. of Patients Chondrosarcoma
3
Leiomyosarcoma
1
Carcinosarcoma (pseudosarcoma)
1
Invasive fibrous tumor
1
Malignant fibrous histiocytoma
1
All malignant
326
Benign Lesions Capillary hemangioma
1
Chondroblastoma
1
Chondroma
2
Fibrous histiocytoma
1
Glomus tumor
1
Granular cell tumor
2
Hamartoma
2
Hemangiomatous malformation of mediastinum
1
Inflammatory pseudotumor (plasma cell granuloma) 1 Leiomyoma
3
Neurogenic tumor
4
Schwannoma
1
Plexiform neurofibroma
1
Peripheral nerve sheath tumor
1
Atypical schwannoma
1
Paraganglioma
1
Pleomorphic adenoma
3
No. of Patients Pyogenic granuloma
1
Squamous papillomas
9
Multiple
5
Solitary
4
Vascular tumor of borderline malignancy
1
All benign
34
Total
360
Full-size table Note the predominance of malignant tumors. Three patients had 2 tumors of different histology. Adapted with permission from Gaissert et al.[5] and [8]
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How Are These Tumors Evaluated? Evaluation of the primary tracheal tumor consists of an assessment of local disease, the confirmation of histology, and clinical staging of regional and distant disease. Although local assessment is facilitated by a precise, thin-section computed tomography aided by sagittal and coronal reconstruction,6 bronchoscopy under general anesthesia provides essential information about the length of diseased and uninvolved trachea. This examination may be conducted with either rigid or fiberoptic bronchoscopes and should include precise measurements of airway length. Where available, endobronchial ultrasound may provide additional information about tracheal wall thickness and extent of extrinsic tumor7; however, we do not yet possess a clear understanding of the role of tracheal endosonography in the staging of tumors. Neck mobility is evaluated on physical examination and related to the length of remaining healthy airway. Biopsy specimens may be obtained during bronchoscopy. Biopsy is not obligatory before resection; short, obstructive lesions can be resected without biopsy, whereas the histologic diagnosis in more extensive tumors may influence the judgment whether a primary tumor is present and resectable. Although the pathologic interpretation may often be straightforward, the diagnosis of adenoid cystic carcinoma is sometimes difficult where this tumor type is rarely seen. How else would one explain that the frequency of the extremely uncommon tracheal adenocarcinoma exceeds 10% in epidemiologic studies,[1] and
of adenoid cystic carcinoma or metastatic disease? Any diagnosis of adenocarcinoma should therefore be reviewed by an experienced pathologist and accompany the review of the radiographs because of the implications for treatment and the estimation of tumor growth and natural history. Clinical evaluation for distant disease consists of standard radiographic studies used in solid tumor staging, including positron emission tomography (PET) and computed tomography of the trunk and computed tomography or magnetic resonance imaging of the brain. In a referral center, less than 10% of all patients with tracheal tumors, selected for assumed resectability, were found to have metastatic disease.8 This proportion is expected to be much higher in unselected patients, thus justifying a detailed metastatic survey in primary malignancies. The value of PET depends on the tumor type and grade; whereas squamous cell carcinomas exhibit uniformly high uptake, the avidity on PET of adenoid cystic or mucoepidermoid carcinoma depends on their degree of differentiation.9 What Therapy Should Be Selected? One may begin by asking why many of these very central tumors are resectable at all, given the immediate proximity to lymphatic channels and important vascular structures. Local invasion of aorta, innominate artery, superior vena cava, or pulmonary artery is uncommon, and esophageal invasion can often be resected be removing invaded muscle alone. The mobile excursion of the trachea relative to the surrounding mediastinal structures may resist early in the natural history fixation by local invasion. The limited rate of lymph node metastasis and distant disease at the time of resection is best understood when considering the size of resected tumors. The mean length of resected trachea at Massachusetts General Hospital (MGH) in adenoid cystic carcinoma was 3.2 cm and in squamous cell carcinoma was 2.4 cm.8 Therefore, by the time obstructive symptoms lead to the diagnosis of a resectable tracheal tumor, neither lymph node spread nor dissemination of disease should be common. Relief of acute obstructive symptoms is best separated from definitive therapy. For the patient in respiratory distress, rapid relief is provided by endobronchial debulking. Such a procedure is expeditiously performed with a rigid bronchoscope under general anesthesia to provide ventilation through the endoscope.10 Although endobronchial laser may be useful for this purpose, airway stenting is not because of the additional injury inflicted by the stent on the tracheal wall. The selection of definitive therapy proceeds from a determination of resectability. There is now enough evidence to state with conviction the superior long-term outcome of segmental tracheal resection in survival and function.[8] and [11] Resection restores a normal airway lumen and does not preclude additional postoperative therapy, nor radiation or chemotherapy. The decision to resect is influenced by tumor length, neck mobility, comorbid factors, and age. There is no universally applicable limit for the maximum resectable length, although resection of more than half of the trachea rarely succeeds. The longer the tumor, the greater should be the emphasis on accurate surgical judgment. At present, the use of prosthetic or biological forms of tracheal replacement is not clinically established,12 but replacement may become available in the future.
What Is the Role of Neoadjuvant Therapy? There is no role for neoadjuvant radiation, and the benefits of neoadjuvant chemotherapy remain untested. No clinical data, not even preliminary reports, support neoadjuvant trimodality therapy. Preoperative radiation impairs tracheal blood supply and delays healing of the tracheal anastomosis. Because tension is observed after any tracheal reconstruction as a function of resected tracheal length, delayed healing translates into a high risk of dehiscence or complete separation of the anastomosis, a life-threatening postoperative complication. This risk would be greatest in those tumors judged most in need of multimodality therapy as long tumors have a larger extramural component. In patients who are referred after preoperative radiotherapy, specific measures are required to support wound healing after resection and include the use of nonradiated vascularized tissue, for example, the omentum, prepared as a pedicled graft to wrap the anastomosis.13 What Are the Indications for Insertion of a Tracheal Stent? Placement of airway stents must be avoided as long as surgical resection remains an option; these stents macerate the normal tracheal wall and are not suitable as a “bridge� to resection. Once resection is eliminated as treatment, several types of airway stents may be considered. Self-expanding metal stents (Ultraflex and Wallstent; Boston Scientific, Natick, MA; Palmaz; Johnson and Johnson, New Brunswick, NJ) are selected because they are easy to insert by fiberoptic bronchoscopy and do not always require general anesthesia. Their greatest risks are dislodgement and concentric strictures above and below the stent; radiation may suppress strictures and granulation formation. The success of these stents is most predictable when the expected survival is limited to 3-6 months. When longer term palliation is sought, we prefer a silicone stent fixed by a side arm located in a tracheal stoma (tracheal T-tube; Hood Laboratories, Pembroke, MA). The T-tube glides inside the airway and exerts pressure on abnormal trachea only; the risk of obstruction and damage to the tracheal wall is therefore lower. Does Segmental Resection for Tracheal Tumors Conform to Oncological Principles? The close spatial relationships in the mediastinum preclude the concept of radical resection in a radial plane, whereas limited tracheal length and mobility restrict the taking of margins along the tracheal axis. So constrained, doubts must arise regarding the completeness of any tracheal resection for neoplastic disease. Indeed, margins are often close or microscopically positive in resections for adenoid cystic carcinoma, the archetypical surgical challenge owing to extensive submucosal spread at the time of diagnosis. In the MGH series, 59% of resections for adenoid cystic carcinoma resulted in positive margins at either tracheal cut end or along the soft tissue.8 In a more complete follow-up of adenoid cystic carcinoma, the survival of patients after resection with microscopically positive airway margins while trailing that with negative tracheal margins was clearly superior to patients with unresectable disease, as shown in Table 2 (Honings J, Gaissert HA, Weinberg AC, et al, unpublished data). The tumor status at the tracheal margin, however, can always be accurately determined. Failure to complete the resection rests not with the method but the anatomy. Most tracheal carcinomas grow beyond the tracheal wall, and tumor is often close to the soft-tissue surface, without invading beyond the confines of resection. These limits imposed on the surgeon resulted early on in the
recommendation for postoperative radiotherapy, today a standard that acknowledges the shortcomings of resection. Table 3 shows the influence of tumor depth and lymphatic invasion on survival after resection of squamous cell carcinoma based on individual pathologic review of resected squamous cell carcinoma (Honings J, Gaissert HA, Ruangchira-Urai R, et al, unpublished data). Although extension beyond the tracheal wall and lymphatic invasion lower survival, their mere presence should not pre-empt surgical therapy. Despite unfavorable anatomic relationships, the existing evidence supports the option of resection.
Table 2. Survival According to Pathologic Subgroups in 108 Cases of Resected Adenoid Cystic Carcinoma at MGH
N o N . o ( . % )
M ea n Sur viv al (y)
P V al u e
Survival (%)
Pathologic Subgroup
1 5 0 y y
1 5 y
2 0 y
Airway resection margins Grossly positive
9
8.3 8.3
56 28 28 28
Microscopically positive
59
54. 13.4 6
75 65 46 33
N o N . o ( . % )
M ea n Sur viv al (y)
P V al u e
Survival (%)
Pathologic Subgroup
1 5 0 y y
1 5 y
2 0 y
40
37. 19.9 0
86 71 64 57
Grossly positive
3
2.8 3.8
50
Microscopically positive
95
88. 0.05 15.4 77 62 47 36 0 0
Negative
10 9.3 21.9
Negative Radial resection margins
10 10 10 10 0 0 0 0
Lymph node metastasis Yes
16
14. 8.4 8
0.01 54 32 16 16 7
No
45
41. 16.8 7
76 66 54 38
No lymph nodes sampled
47 43. 17.2
91 80 71 71
N o N . o ( . % )
M ea n Sur viv al (y)
P V al u e
Survival (%)
Pathologic Subgroup
1 5 0 y y
1 5 y
2 0 y
5 Overall
10 10 16.0 8 0.0
78 65 53 43
Full-size table Note the intermediate survival of patients with microscopically positive airway and radial margins. Negative versus positive (n = 68), P = 0.028. Gross positive versus gross negative (n = 99), P = 0.026. Microscopic positive versus negative, P = 0.069. All three compared, P = 0.017.
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Table 3. Survival According to Depth of Invasion by the Primary Tumor and Presence of Lymphatic Invasion in 59 Cases of Resected Squamous Cell Carcinoma
N o N . o ( . % )
Me an Sur viv al (y)
P Surv Va ival lu (%) e
Pathologic Subgroup
1 5 0 y y Depth of invasion Carcinoma in situ
2
3.4 n.a.
0.00 10 10 1 0 0
Infiltrating lamina propia
5
8.5 7.6
75 25
Abutting or extending between cartilage
14
23. 6.0 7
50 25
Invading beyond cartilage
11
18. 7.1 6
50 38
Invading peritracheal fibroadipose tissue
16
27. 7.7 1
53 31
Abutting soft-tissue resection margin
6
10. 2.1 2
Invading into thyroid gland
5
8.5 1.4
Lymphatic invasion
0
N o N . o ( . % )
Me an Sur viv al (y)
P Surv Va ival lu (%) e
Pathologic Subgroup
1 5 0 y y Yes
22
37. 4.6 3
0.04 24 24 9
No
37
62. 7.6 7
60 31
Overall
59
10 6.5 0.0
46 27
Full-size table Presence of tumor outside the tracheal wall and in the lymphatics diminishes long-term survival. Lymphatic invasion proven by either positive lymph node biopsy or lymphatic invasion on histologic examination.
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When Is Resection Not Indicated?
Patients in whom a primary tracheal anastomosis after tumor resection is judged not to be feasible, patients with disease locally invasive into organs other than the esophagus, and those with metastatic disease are considered unresectable. They are candidates for primary radiation or radiochemotherapy to palliate breathing.14 Their survival is short for high-grade bronchogenic carcinoma and sarcoma, whereas adenoid cystic carcinoma has a slower rate of progression and often responds to radiation with prolonged survival despite the evolution of metastatic disease. Although there is support for resecting tracheal invasion by slow-growing thyroid carcinoma to palliate airway obstruction or bleeding in the presence of metastatic disease, its value for the individual patient with metastatic adenoid cystic carcinoma must be questioned. What Length of Resection Is Safe? This question, although of greatest interest for each individual patient, has no generally valid answer. Instead, the following variables are considered: patient age, mobility of the neck, body weight and build, and endoscopically measured length of lesion. A composite assessment of the first 3 factors indicates how high the trachea will rise out of the chest during maximal neck extension and whether complete mobilization of the trachea together with surgical release maneuvers would add sufficient length for safe reconstruction; these considerations will need to be balanced with the anticipated length of resection. Planned resections of less than 4 cm of trachea will almost always be tolerated, unless incomplete mobilization or fixed cervical kyphosis raises anastomotic tension. Which Factors Increase the Risk of Operative Complications? The fate of the anastomosis is the primary determinant of operative success in strictly tracheal resections. Carinal resections have further risks related to an additional anastomosis or major pulmonary resection. The greater complexity is reflected in a higher operative mortality (tracheal resection 3.9%, carinal resection 16% in the MGH series).8 The results of 900 tracheal resections for various indications were analyzed for factors predicting anastomotic complications.15 In stepwise analysis, these risk factors were reoperation, diabetes, resection of more than 4 cm of trachea, laryngotracheal resection, young age, and the presence of a tracheostomy at the time of resection. Figure 1 shows the increase of anastomotic complications as a function of resected tracheal length. Tumor as the indication for resection, in contrast, did not predict anastomotic failure. These observations emphasize the importance of a well-executed first tracheal resection.
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Figure 1. Anastomotic complications are a function of length in 800 first resections (diagonal stripes) and 101 reoperations (open bars) at MGH. (Reprinted with permission from Wright et al.15)
Should Mediastinal Lymph Node Dissection Be Part of the Resection? Although complete mediastinal lymph node dissection appears desirable for precise staging, tracheal devascularization accompanies the radical removal of peritracheal lymph nodes to create a thoracic version of Heisenberg's uncertainty principle: confidence may be placed in either staging or healing, but not both. The segmental tracheal blood vessels that also support the peritracheal lymph nodes must be preserved.16 The lymph nodes immediately next to tumor are often part of the specimen, but oncological purists expecting a systematic nodal staging will be disappointed. From existing data, it is obvious that confirmed lymph node metastasis lowers long-term survival; indeed survival beyond 10 years in lymph-node-positive adenoid cystic carcinoma was not observed at MGH. Which Patients Require Postoperative Adjuvant Therapy? The evidence for adjuvant therapy is incomplete and circumstantial. The recommendation for additional local therapy is based on the compromised completeness of almost all resections for intermediate or high-grade malignant tumors. Low-grade tumors, such as carcinoid tumor or well-differentiated mucoepidermoid carcinoma, do not receive radiation. At MGH, every patient with aggressive malignancy who has completed recovery with an intact tracheal anastomosis receives mediastinal radiation with a dose of 54 Gy.17 Some patients have received higher doses as they were treated outside MGH. Radiotherapy should be delayed if there are concerns about the anastomosis, and treatment is usually not started for 2 months after operation. What Follow-Up Is Recommended After Resection? Continued follow-up of these patients has the purpose of monitoring for locoregional and distant recurrence as well as second primary cancers. In the MGH series, 27 of 135 patients with squamous cell carcinomas of the trachea had prior carcinomas of the lung, head, or neck. Second primary tumors therefore threaten these patients in the future. Regular surveillance computed tomography and bronchoscopy should be offered to all patients to diagnose locoregional recurrence early, even though second resections for recurrent tumor would rarely be considered. References 1 M.P. Manninen, J.S. Pukander and M.K. Flander et al., Treatment of primary tracheal carcinoma in Finland in 1967-1985, Acta Oncol 32 (1993), pp. 277–282. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (20) 2 P.B. Licht, S. Friis and G. Pettersson, Tracheal cancer in Denmark: A nationwide study, Eur J Cardiothorac Surg 19 (2001), pp. 339–345. Article |
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3 J. Honings, J.A. van Dijck and A.F. Verhagen et al., Incidence and treatment of tracheal cancer: A nationwide study in The Netherlands, Ann Surg Oncol 14 (2007), pp. 968–976. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (9) 4 C.M. Gelder and M.R. Hetzel, Primary tracheal tumours: A national survey, Thorax 48 (1993), pp. 688–692. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (43) 5 H.A. Gaissert, H.C. Grillo and M.B. Shadmehr et al., Uncommon primary tracheal tumors, Ann Thorac Surg 82 (2006), pp. 268–272. 6 G.R. Ferretti, C. Bithigoffer and C.A. Righini et al., Imaging of tumors of the trachea and central bronchi, Radiol Clin North Am 47 (2009), pp. 227–241. Article |
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7 F. Herth, A. Ernst and M. Schulz et al., Endobronchial ultrasound reliably differentiates between airway infiltration and compression by tumor, Chest 123 (2003), pp. 458–462. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (62) 8 H.A. Gaissert, H.C. Grillo and M.B. Shadmehr et al., Long-term survival after resection of primary adenoid cystic and squamous cell carcinoma of the trachea and carina, Ann Thorac Surg 78 (2004), pp. 1889–1897. Abstract | Article | Cited By in Scopus (43)
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9 C.M. Park, J.M. Goo and H.J. Lee et al., Tumors in the tracheobronchial tree: CT and FDG PET features, Radiographics 29 (2009), pp. 55–71. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (6) 10 D.J. Mathisen and H.C. Grillo, Endoscopic relief of malignant airway obstruction, Ann Thorac Surg 48 (1989), pp. 469–473. 11 J.F. Regnard, P. Fourquier and P. Levasseur, Results and prognostic factors in resections of primary tracheal tumors: A multicenter retrospective study; the French Society of Cardiovascular Surgery, J Thorac Cardiovasc Surg 111 (1996), pp. 808–813. 12 H.C. Grillo, Tracheal replacement: A critical review, Ann Thorac Surg 73 (2002), pp. 1995– 2004. Abstract | Article |
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13 D.D. Muehrcke, H.C. Grillo and D.J. Mathisen, Reconstructive airway operation after irradiation, Ann Thorac Surg 59 (1995), pp. 14–18. Abstract | Scopus | Cited By in Scopus (24)
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14 J.N. Fields, G. Rigaud and B.N. Emami, Primary tumors of the trachea: Results of radiation therapy, Cancer 63 (1989), pp. 2429–2433. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (39) 15 C.D. Wright, H.C. Grillo and J.C. Wain et al., Anastomotic complications after tracheal resection: Prognostic factors and management, J Thorac Cardiovasc Surg 128 (2004), pp. 731– 739. Abstract | Article |
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16 J.R. Salassa, B.W. Pearson and W.S. Payne, Gross and microscopical blood supply of the trachea, Ann Thorac Surg 24 (1977), pp. 100–107. Abstract | Scopus | Cited By in Scopus (64)
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17 J.J. McGrath, N.C. Choi and D.J. Mathisen et al., Role of radiation therapy in the management of tracheal tumors, Int J Radiat Oncol Biol Phys 51 (2001), p. 344. Abstract | Article |
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Address reprint requests to Henning A. Gaissert, MD, Massachusetts General Hospital, Blake 1570, Fruit Street, Boston, MA 02114