Ann Thorac Surg 2007;83:1952-1959
© 2007 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Segmental Laryngotracheal and Tracheal Resection for Invasive Thyroid Carcinoma
Henning A. Gaissert, MD*,
Jimmie Honings, MS,
Hermes C. Grillo, MD
,
Dean M. Donahue, MD,
John C. Wain, MD,
Cameron D. Wright, MD,
Douglas J. Mathisen, MD
Division of Thoracic Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Accepted for publication January 29, 2007.
* Address correspondence to Dr Gaissert, Massachusetts General Hospital, Blake 1570, Fruit St, Boston, MA 02114 (Email: hgaissert{at}partners.org).
Presented at the Poster Session of the Forty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Jan 29–31, 2007.
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Abstract
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Background: Laryngotracheal invasion worsens prognosis in patients with thyroid carcinoma. The extent of resection is controversial.
Methods: We performed a retrospective study of patients with thyroid carcinoma and invasion of the larynx or trachea between 1964 and 2005.
Results: Eighty-two patients, mean age 64 years and 50% female, underwent segmental airway resection. Differentiated carcinoma was present in 76% (62 of 82 patients), prior tracheal "shave" procedures in 40% (33 of 82 patients), transmural invasion in 58% (48 of 82 patients), and preoperative vocal cord paralysis in 35% (29 of 82 patients). There were 29 tracheal and 40 laryngotracheal resections (reconstruction group: 69 patients); 5 underwent laryngectomy, 7 cervical exenteration, and 1 tracheal resection after exenteration (salvage group: 13 patients). Operative mortality was 1.2% (1 of 82 patients) and anastomotic dehiscence 4.3% (3 of 69 patients). Tracheostomy was permanent in 4.3% (3 of 69 patients). Mean follow-up was 6.1 years. After reconstruction, mean survival was 9.4 years and 10-year survival was 40%; after salvage, these were 5.6 years and 15%, respectively. In differentiated carcinoma, thyroidectomy, immediate shave procedure, and delayed (mean, 67 months) resection of airway recurrence in 15 patients resulted in overall and disease-free survival of 13.1 and 5.1 years, respectively, compared with 17.9 and 14.6 years, respectively, after thyroidectomy and early airway resection in 11 patients. Airway symptoms, metastases at presentation, recurrent disease, and salvage operation were associated with decreased survival; airway resection early after thyroidectomy, complete resection, and well-differentiated tumors were associated with improved prognosis.
Conclusions: Segmental airway resection for invasive thyroid cancer is safe, preserves the voice, and relieves airway obstruction. Complete resection of laryngeal and tracheal invasion during or early after thyroidectomy is associated with improved survival.
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Introduction
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The prognosis of patients with well-differentiated thyroid carcinoma is excellent, with a 10-year survival rate close to 90% after surgical resection [1]. Laryngeal or tracheal invasion, found in approximately 6% of thyroid carcinoma, is an independent predictor of death [2]. Advanced invasion may produce hemoptysis, hoarseness, and dyspnea and leads to life-threatening complications such as airway hemorrhage and suffocation. Indeed, airway obstruction is the cause of death in 50% of patients with thyroid carcinoma [3]. These observations emphasize the importance of local control in both early and advanced airway invasion.
In thyroid carcinoma, complete resection of local disease provides the longest survival and the best palliation. In pursuit of this goal, segmental laryngotracheal and tracheal resection have been applied at Massachusetts General Hospital to patients with superficial and transmural invasion of the airway. Although segmental resection is widely accepted for transmural invasion [2, 4–6], adherence to the trachea or larynx as a result of superficial invasion, in contrast, often is treated with tangential excision from the airway ("shaving"), even though this technique violates oncologic principle and falls short of complete resection. Long-term evidence supporting tangential excision is absent, and recurrence is common [7–9]. Our approach was previously reported [10, 11] and is now updated to analyze long-term results in a larger group of patients.
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Patients and Methods
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Patient Selection
Between 1964 and July 2005, 113 patients were seen with thyroid carcinoma invading the larynx or trachea. Thirty-one patients (27.4%) were excluded from further analysis. Disease was not resected in 28 patients owing to extensive local disease that either did not compromise the airway or could not be resected because of prior high-dose radiation, advanced distant disease, or refusal of surgery. Three patients in the early experience of Grillo and colleagues [10, 11] were excluded because their treatment is now obsolete: 2 had skin tube reconstruction of the trachea using cervical skin supported with plastic rings, a technique not used since and considered unnecessary; 1 who presented after high-dose (78 Gy) external beam radiation elsewhere experienced anastomotic dehiscence after tracheal reconstruction. Two of the 3 patients were operative deaths. The remaining 82 patients (72.6%) constitute the study population.
The Massachusetts General Hospital institutional review board approved previous retrospective studies and the most recent protocol (No. 2005-P-001254/3) in August 2005. Consent was received from patients before obtaining follow-up information.
The 82 patients were classified according to clinical presentation and extent of disease. Twenty-eight patients presented with locoregional recurrent disease late after prior thyroidectomy (delayed presentation), whereas 11 patients were either referred for tracheal resection directly after thyroidectomy (8 patients) or underwent airway resection (3 patients) at the time of thyroidectomy (early presentation). There were 26 patients without previous thyroidectomy who had either airway obstruction or hemoptysis as a result of transmural disease (symptomatic presentation). Finally, 17 patients had symptomatic airway disease and distant metastasis (palliative presentation). In the early presentation group, no patient had hemoptysis or dysphagia and only 1 who at first refused resection had dyspnea.
Pathology reports, operative reports, and hospital charts were reviewed. The survival period began on the day of operation at Massachusetts General Hospital, except where otherwise indicated.
Determination of Resectability
Patients underwent assessment of locoregional and distant metastatic disease before resection. Radiographic evaluation included conventional tracheal tomography in the early experience and computed tomography thereafter. Limited presumed or known pulmonary metastasis was not a contraindication to resection. Bronchoscopy was performed before resection to assess the presence and extent of luminal invasion. Tracheal resection was considered when complete resection of gross airway disease appeared feasible. Symptoms caused by airway obstruction or hemoptysis were an indication for palliative resection even when grossly positive peritracheal margins or pulmonary metastasis were noted. A tumor was considered unresectable when advanced metastatic disease was present, the length of involved airway at bronchoscopy precluded primary anastomosis or mediastinal tracheostomy, or invasion of vital adjacent organs was found during operative exploration.
Types of Resection
For tracheal resection, a segment of trachea was removed with end-to-end reconstruction. For laryngotracheal resection, the tumor was removed with a portion of infraglottic larynx, and the remaining trachea was shaped to reconstruct the laryngeal defect. These procedures belonged to the reconstruction group and required at least one functioning recurrent laryngeal nerve not involved with tumor. When preoperative unilateral vocal cord paralysis was present, the contralateral thyroid lobe was often preserved. Invasion of esophageal muscle or mucosa was treated with tangential resection of full-thickness wall or muscle coat. The procedures in the salvage group, cervicomediastinal exenteration or laryngectomy alone, were considered in patients who had airway compromise as a result of malignant airway stricture or aspiration with or without impaired swallowing. Exenteration and intestinal substitution was performed when the larynx could not be salvaged and consisted of laryngectomy, resection of trachea, esophagectomy, total thyroidectomy, and usually parathyroid resection with creation of a cervical or mediastinal tracheal stoma. Locoregional lymph nodes were resected except for paratracheal nodes not immediately adjacent to the tumor, which were preserved to protect the tracheal blood supply. Absence of tumor at the airway margins was confirmed by frozen section unless the limits of resection had been reached and no additional trachea could be removed without sacrificing the larynx. The resection was judged to be complete when the airway margins were found to be free of disease, the soft tissue margins were not grossly involved with the tumor, and no statement in the operative note indicated that gross tumor remained.
A shave resection as described to us by referring surgeons consisted of tangential excision of the tumor and thyroid gland sometimes associated with scraping the thinned-out tracheal wall.
Hypoparathyroidism was considered a complication when absent on admission and when the patient was discharged while taking calcium and calcitriol. Temporary hypoparathyroidism with a calcium or calcitriol requirement at the time of discharge that resolved during follow-up was not considered in reporting complications after reconstruction or salvage.
Tumor Data
Tumor dimension in the airway axis, depth of invasion, and the presence of tumor at the airway or radial margins were recorded from a review of pathology reports. Positive airway margins indicated true residual, most often microscopic, tumor. Tumor involvement of excised lymph nodes was noted. To analyze the extent of invasion, the Shin staging system was used for well-differentiated (papillary and follicular carcinoma) and poorly differentiated thyroid carcinoma [12].
External Beam Radiotherapy and 131-Iodine Therapy
Postoperative radiotherapy or oral radioactive iodine therapy was administered selectively when the resection was incomplete. After bronchoscopic assessment of anastomotic healing, a recommended dose of 54 Gy to the neck and superior mediastinum was administered 6 to 8 weeks after resection, after bronchoscopic check of the anastomosis. Most patients received treatment outside Massachusetts General Hospital, and the decision to administer adjuvant therapy was made elsewhere.
Follow-Up
Patients and their physicians were contacted for follow-up information. The social security death index was searched. Patients were determined to have died if name, date of birth, and social security number matched.
Statistical Analysis
Overall and disease-free survival after airway resection were calculated using the Kaplan–Meier procedure with the log rank test implemented in the SPSS 12.0 statistical software program (SPSS Inc, Chicago, IL). In patients presenting with airway recurrence only, the date of tracheal resection concluded the disease-free survival after previous thyroidectomy. To compare overall and disease-free survival after thyroidectomy with shave excision of the airway to thyroidectomy with immediate or early tracheal resection, the survival period was calculated from the date of first thyroidectomy.
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Results
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Patient Characteristics
The characteristics of 82 patients are listed in Table 1
according to the type of resection and airway reconstruction. Overall, well-differentiated tumors were found in 62 patients (75.6%), in 72.5% of patients undergoing reconstruction, and in only 38.5% of the salvage group. Pathologic evaluation identified transluminal tumors (Shin stage IV) in 48 patients (58.5%).
Operative Treatment
In the reconstruction group, 40 patients underwent laryngotracheal resection (58%) and 29 tracheal resection (42%). One patient had a tracheal resection for primary tracheal neoplasm with skin tube reconstruction 31 years before, and presented with a new papillary thyroid carcinoma invading her skin tube. She underwent resection of thyroid and skin tube with primary tracheal end-to-end anastomosis. A single patient had a wedge resection of the anterior tracheal wall early in the experience. Three patients (4.3%) underwent concomitant lateral excision of full-thickness esophageal wall with primary closure, and 10 patients (14.5%) had excision of esophageal muscle for tumor invasion. The length of the resected airway measured 1.5 to 6.0 cm (mean, 3.2 cm). Resection was complete in 36 patients (52.2%). In 33 patients with incomplete resection, 4 had residual gross disease. Microscopic positive resection margins in 29 patients consisted of 25 positive airway margins, 3 uncertain airway margins with positive soft tissue margins, and 1 positive soft tissue margin only. Residual gross disease was caused by distant metastases in 3 patients and the single wedge resection in 1 patient. Five patients with incomplete resection had prior total thyroidectomy; all others underwent thyroidectomy.
In the salvage group, 7 of 13 patients underwent cervical exenteration, 4 had laryngectomy without esophagectomy, 1 had laryngectomy with partial lateral esophagectomy, and 1 underwent tracheal resection after exenteration and tracheostomy. In patients with exenteration, the larynx was spared in 1 patient, and the esophagus was reconstructed with colon interposition in 3, gastric pull-up in 2, a pectoralis flap in 1, and primary reconstruction in 1. Esophageal muscle was partly excised in 3 of 4 patients undergoing laryngectomy without esophagectomy. Mean length of resected airway was 9.1 cm (range, 3.0 to 15.5 cm, the latter length including the larynx). Complete resection was accomplished in 8 patients (61.5%).
Complications
The single death resulted from airway obstruction as a result of glottic edema after laryngotracheal resection. Table 2
lists the complications after reconstruction and salvage. Anastomotic dehiscence occurred in 3 patients (4.3%) in the reconstruction group. Two had laryngotracheal reconstruction and were treated with temporary tracheostomy for less than a month. The third patient, in whom 4.5 cm of trachea was resected with laryngeal release, died 7 months later of respiratory failure. After salvage, 2 patients with separation of the tracheal stoma from the skin were treated with a stomal stent. Permanent hypoparathyroidism occurred in only 2 patients after salvage (15.4%) and 3 after reconstruction (4.3%), whereas additional patients required temporary calcium substitution with or without calcitriol. Four of 6 patients with postoperative aspiration experienced pneumonia. Postoperative dysphagia was observed in 3 patients, of whom 2 had lateral esophageal resection.
Five of 6 patients in the reconstruction group with postoperative bilateral vocal cord paralysis had preoperative unilateral paralysis, and the contralateral recurrent laryngeal nerve was preserved in 4. Four of 6 had temporary tracheostomy from 1 to 9 months: 3 required vocal cord lateralization and 1 had spontaneous vocal cord recovery less than 1 month after operation. The indications for temporary tracheostomy in 13 of 69 patients (18.8%; mean duration, 2 months; range, 0 to 9 months) were bilateral vocal cord paralysis in 4, anastomotic dehiscence in 2, aspiration pneumonia in 1, and dyspnea caused by subglottic edema in 1. Five temporary tracheostomies were placed for protective reasons during the operation. Three patients required permanent tracheostomy (4.3%): 1 patient with anastomotic dehiscence and respiratory failure described above, 1 who died 10 months after the operation of metastatic disease, and 1 patient who died 2 months after resection of myocardial ischemia. The incidence of complications decreased during four decades to 25.8% between 1996 and 2005.
Postoperative adjuvant therapy is detailed in Table 1.
Long-Term Results
The mean follow-up period was 6.1 years (range, 2 months to 24 years). Follow-up was complete in all patients. Of 65 patients surviving the operation without permanent tracheostomy, 11 patients had only local recurrence treated with an airway tube in 4, 7 patients had distant recurrence only, 6 patients had both distant and local recurrence treated with an airway tube in 2, 5 patients with distant metastasis at operation did not have local recurrence, and of 9 other patients with distant disease at operation who later developed local recurrence, 2 required an airway tube. In total, 8 patients received an airway tube because of local recurrence. Table 3
shows overall and disease-free survival in the reconstruction and salvage groups. Figure 1
depicts the survival curves of reconstruction and salvage groups.
Sixty-two patients with well-differentiated thyroid carcinoma were analyzed separately. Overall and disease-free survival is shown in Table 4. After complete resection, mean survival was 13.8 years and survival at 15 years 44%. As shown in Figure 2, after incomplete resection mean survival was only 5.3 years and none of the patients is alive at 15 years (p < 0.0001). Disease-free survival was also significantly higher in patients with complete resection (p = 0.0053).
As shown in Figure 3, there is a marked difference in survival between asymptomatic patients undergoing airway resection at the time of thyroidectomy or early thereafter in comparison with all other groups. The prognosis after delayed, symptomatic, or palliative presentation is worse compared with patients with early presentation (p = 0.0417). Palliative resection, however, in some patients is compatible with long-term survival. Three patients are presently alive 5, 11, and 21 years after palliative airway resection.
Survival After Thyroidectomy
We identified 15 patients with well-differentiated histologic classification and recurrent disease after shave procedure (delayed airway resection group) among 28 with prior thyroidectomy and compared them with 11 patients who underwent early airway resection (early airway resection group). Characteristics of these groups are described in Table 5. Three of the 15 patients belonged to a low-risk age group [13] at the time of thyroidectomy (2 women younger than 50 years, 1 man younger than 40 years of age), and 11 (73.3%) had received radioactive iodine therapy after thyroidectomy. One patient, counted as an early resection, was referred immediately after thyroidectomy and tracheostomy, but did not present for laryngotracheal resection until 14 months later.
Figure 4
compares the overall survival of patients with early shave procedure and late airway resection for recurrence after a mean delay of 67 months with those who underwent immediate or early airway resection. Mean survival calculated from the date of thyroidectomy in the delayed group was 13.1 years and 20-year survival was 24%, lower than after early airway resection. Disease-free survival after early airway resection was significantly higher (p = 0.0092) than after delayed resection (14.6 versus 5.1 years; Fig 5), and disease-free survival at 20 years was also significantly higher (50% versus 0%).
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Comment
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The present study confirms in a large group of patients the safety and effectiveness of segmental tracheal resection noted in the earlier reports from our unit. With increasing experience and when considering presently applied indications and procedures, the operative mortality has declined to 1.2% and the complication rate decreased from 44% to 26% during the last three decades. These results are substantiated by Ozaki and associates [14], Tsumori and coworkers [1], and Ishihara and colleagues [3], who saw no operative deaths in a combined 58 segmental tracheal resections. Operative risk should therefore not serve as the reason to forgo complete resection of thyroid cancer involving the airway, although operative risk remains a function of surgical experience [15, 16].
Shave or tangential excision appears to be common and preferred surgical management for airway invasion. More than half of all patients in our study treated with segmental laryngotracheal and tracheal resection (46 of 82 patients) had prior resection of thyroid carcinoma, and 33 of these underwent so-called shave procedures. The proponents of shave procedures point to lack of data on the prognosis of airway invasion, to available adjuvant external beam therapy and radioactive iodine, and to concerns about quality of life after tracheal resection. Czaja and associates [2] compared 34 patients who underwent complete surgical resection of tumor with 75 patients who had shave excision and found no differences in survival between both groups. Nishida and colleagues [5] agreed that survival in 40 patients with deep tracheal invasion treated with tracheal resection was no different from that in 13 patients with superficial invasion treated with a shave. Because a tracheal specimen does not accompany the thyroid after tangential excision, we do not know the presence or depth of invasion in the two studies above. There is now sufficient evidence to state that depth of invasion predicts outcome [1, 12]. In long-term studies, other authors emphasize the high risk of recurrence after excision of airway invasion by thyroid carcinoma. Six of 35 patients with superficial tracheal adherence treated with tracheal shaving in a study by McCarty and associates [4] had local recurrence after 10 years (17%). Seven of 16 patients after shave procedures treated with radioactive iodine or external beam therapy after operation died of disease 3.6 years after surgery, and disease was controlled in only 25% of patients after 5.9 years [7]. In contrast, local airway recurrence after segmental tracheal resection is infrequent. Monitoring 31 patients for a mean of 10.6 years after resection, Nakao and colleagues [17] found only 2 local among 12 total recurrences (6.5%). The high recurrence rates reported above by Park and associates [7] occurred despite radioactive iodine or external beam radiotherapy. In our group of 15 delayed airway resections for well-differentiated carcinoma, 11 patients had received radioactive iodine after thyroidectomy (73.3%). We observed airway recurrence requiring tracheostomy in 12.3% (8 of 65 patients). Because the surgical technique to achieve complete resection is well established, a reliance on radioactive iodine or external beam radiotherapy after shave procedures is difficult to justify and may be futile. Finally, the quality of life after segmental airway resection in patients with thyroid carcinoma involving the airway is higher than before operation [16, 18].
Immediate or early complete resection of laryngotracheal invasion is followed by the longest overall and disease-free survival. We found complete resection a significant prognostic factor, and positive airway margins defined a majority of patients with incomplete resection (79%, 26 of 33 patients). We also identified in this retrospective analysis a comparable set of patients mainly distinguished by the date of airway resection after thyroidectomy. When determining survival from the date of the first thyroidectomy as the start of follow-up, and after adding a mean survival period of more than 5 years to patients who presented after shave resection for delayed airway resection, we found a persistent benefit of early airway resection for differentiated thyroid carcinoma. The two groups had minor differences in the proportion of female patients, although not in age at first resection or absence of distant metastasis. Overall survival calculated from the date of first thyroidectomy was longer after early airway resection, although not significant owing to sample size. Disease-free survival, however, was significantly higher after early resection, with 10- and 20-year disease-free survival rates of 67% and 50%, respectively, whereas after delayed resection disease-free survival at 10 years was only 7% and none of the patients was alive without disease after 20 years. The purpose of such comparison, exposed as it may be to selection bias, is of course not to replace, but to provoke, an overdue prospective multi-institutional study of the surgical options in laryngotracheal invasion.
Palliative resection offers benefit in terms of survival or quality of life in few solid tumors. The patients presenting with distant metastasis had a mean survival of 6 years after segmental airway resection. Even in the presence of distant metastasis, segmental airway resection may prolong survival, control disease, and lead to long-term survival in some patients [19]. We therefore continue to apply palliative tracheal resection in carefully selected patients.
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Footnotes
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Doctor Grillo died on Oct 14, 2006. 
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References
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- Tsumori T, Nakao K, Miyata M, et al. Clinicopathologic study of thyroid carcinoma infiltrating the trachea Cancer 1985;56:2843-2848.[Medline]
- Czaja JM, McCaffrey TV. The surgical management of laryngotracheal invasion by well-differentiated papillary thyroid carcinoma Arch Otolaryngol Head Neck Surg 1997;123:484-490.[Medline]
- Ishihara T, Yamazaki S, Kobayashi K, et al. Resection of the trachea infiltrated by thyroid carcinoma Ann Surg 1982;195:496-500.[Medline]
- McCarty TM, Kuhn JA, Williams Jr WL, et al. Surgical management of thyroid cancer invading the airway Ann Surg Oncol 1997;4:403-408.[Abstract]
- Nishida T, Nakao K, Hamaji M. Differentiated thyroid carcinoma with airway invasion: indication for tracheal resection based on the extent of cancer invasion J Thorac Cardiovasc Surg 1997;114:84-92.[Abstract/Free Full Text]
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- Grillo HC, Zannini P. Resectional management of airway invasion by thyroid carcinoma Ann Thorac Surg 1986;42:287-298.[Abstract]
- Shin DH, Mark EJ, Suen HC, et al. Pathologic staging of papillary carcinoma of the thyroid with airway invasion based on the anatomic manner of extension to the trachea: a clinicopathologic study based on 22 patients who underwent thyroidectomy and airway resection Hum Pathol 1993;24:866-870.[Medline]
- Cady B, Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma Surgery 1988;104:947-953.[Medline]
- Ozaki O, Sugino K, Mimura T, et al. Surgery for patients with thyroid carcinoma invading the trachea: circumferential sleeve resection followed by end-to-end anastomosis Surgery 1995;117:268-271.[Medline]
- Kim KH, Sung MW, Chang KH, et al. Therapeutic dilemmas in the management of thyroid cancer with laryngotracheal involvement Otolaryngol Head Neck Surg 2000;122:763-767.[Medline]
- Nakao K, Kurozumi K, Nakahara M, et al. Resection and reconstruction of the airway in patients with advanced thyroid cancer World J Surg 2004;28:1204-1206.[Medline]
- Nakao K, Kurozumi K, Fukushima S, et al. Merits and demerits of operative procedure to the trachea in patients with differentiated thyroid cancer World J Surg 2001;25:723-727.[Medline]
- Sywak M, Pasieka JL, McFadden S, et al. Functional results and quality of life after tracheal resection for locally invasive thyroid cancer Am J Surg 2003;185:462-467.[Medline]
- Musholt TJ, Musholt PB, Behrend M, et al. Invasive differentiated thyroid carcinoma: tracheal resection and reconstruction procedures in the hands of the endocrine surgeon Surgery 1999;1261078–7.
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Abstract
Introduction
