Introduction
Well-differentiated thyroid cancer usually confers a good prognosis, with the 10-year survival rates for those patients with papillary and follicular variants being over 90 per cent after appropriate medical and surgical management. Generally, these treatment regimens are also associated with low morbidity, especially in those patients with early stage disease.Reference Brennan, Bergstralh, van Heerden and McConahey1, Reference Hay, McConahey and Goellner2 Patients presenting with advanced stage disease, however, necessitate a shift in the treatment paradigm; often more aggressive surgery is required and this is associated with concomitant increases in potential morbidity.
It has been reported that between 7 and 16 per cent of patients may present with evidence of locally invasive thyroid cancer.Reference Brennan, Bergstralh, van Heerden and McConahey1, Reference Batsakis3 Extrathyroidal extension and local invasion, together with other prognostic factors, such as age (older than 45 years), sex (being male), histological subtype, lymphatic invasion, tumour size, distant metastases and residual macroscopic disease at the time of primary surgery, have all been associated with an increased risk of tumour recurrence.Reference Honings, Stephen, Marres and Gaissert4, Reference Czaja and McCaffrey5 This, in turn, confers a worse overall survival prognosis for the patient. Therefore, effective surgical management of the primary disease is central to the initial management of this patient group.
Generally, patients with locally advanced disease involving the laryngotracheal complex are managed using one of three different surgical approaches: (1) conservative ‘shave’ techniques, aimed at minimising surgical morbidity; (2) full thickness window resections with reconstruction using local soft tissue flaps; and (3) more aggressive full segmental sleeve resection and re-anastomosis.Reference Lipton, McCaffrey and van Heerden6–Reference Friedman8 Full thickness resections enable a surgical margin to be taken and examined pathologically.
We present a series of three patients with locally advanced, well-differentiated thyroid cancer involving airway cartilaginous structures who were treated with full thickness window resection of the involved airway and reconstruction using a non-vascularised composite nasal septal graft. In this patient group, we made an attempt to marry the benefit of full thickness resection with that of avoidance of circumferential tracheal resection.
Materials and methods
Surgical technique
The surgical setup is as for septoplasty. The contralateral nasal septum (from which the mucosa is being harvested) is infiltrated with 1 per cent lignocaine and 1:80 000 adrenaline to facilitate dissection. The composite nasal septal graft is harvested transnasally, leaving a 1 cm caudal and dorsal strut for nasal tip support, and leaving the contralateral mucoperichondrial flap intact. The quadrangular cartilage is separated from the perpendicular plate of the ethmoid bone and vomer, and the cartilage is removed; the adjacent overlying mucosa remains intact. The composite nasal septal graft is then orientated so that the anterior portion of the graft is positioned inferiorly. Full thickness linear cuts are made through the cartilage to enable the graft to be curved if necessary. A pledget soaked with co-phenylcaine (phenylephrine and lignocaine) is placed for the remainder of the operation and then removed. Packs are avoided in the nose. The patients are subsequently advised to use saline douches from the 3rd post-operative day, for 7 days. Following orientation, the graft is sutured into position using 3.0 polypropylene, clear monofilament (Prolene®) sutures placed through the cartilage, avoiding mucosa.
Tracheotomy was not necessary in our patient series. Non-suction drains were placed at the end of the procedure. Normal diet was resumed on the 1st day post-operatively. Follow-up bronchoscopies were carried out between two and four weeks post-operatively.
Case reports
Case one
A 55-year-old female was referred for further surgery following total thyroidectomy for a Hürthle cell variant of invasive papillary thyroid carcinoma. At the time of surgery, the surgeon observed the tumour to be encompassing the right recurrent laryngeal nerve and reported superficial invasion into the upper aspect of the trachea. Macroscopic disease was left on the trachea. A subsequent magnetic resonance imaging (MRI) scan revealed a nodular opacity adjacent to the cricoid and involving the first tracheal ring of the right side. Bronchoscopy findings were normal.
A planned re-exploration of the neck was performed. This revealed a granular abnormality overlying the first tracheal ring and lower part of the cricoid cartilage. A full thickness resection of the abnormality (with frozen section confirmation of margins) was performed, with a resultant defect measuring 18 mm × 10 mm. A composite nasal septal graft was harvested via a transnasal approach and was sutured in place using size 3.0 Prolene sutures. The patient was discharged following the removal of drains 2 days post-operatively. A follow-up bronchoscopy was performed after three weeks; this revealed healthy looking graft mucosa, with no evidence of airway narrowing.
Formal histopathology revealed papillary thyroid carcinoma invading the tracheal cartilage and extending focally to the submucosa. Despite clear frozen section margins, paraffin sections revealed tumour abutting the lateral margin of the specimen. The patient subsequently underwent a course of therapeutic radioiodine, and her disease currently remains in remission. An MRI scan of the neck was performed, which revealed no evidence of recurrence. Furthermore, the most recent tests (performed two years after treatment) revealed thyroglobulin levels of 1.2 µg/l, with negative antibodies.
Case two
A 62-year-old male presented with a fixed mass over the upper right part of his trachea. He had previously undergone right hemithyroidectomy for a follicular variant of papillary thyroid carcinoma (22 years earlier), and had been declared clear of disease in 2003. His vocal fold function was normal. An MRI scan revealed a 30 mm mass in the right thyroid bed, with suspicion of superficial invasion of the tracheal cartilages. Fine needle aspiration findings were consistent with papillary thyroid carcinoma. A computed tomography (CT) scan revealed multiple small nodules bilaterally, consistent with metastatic pulmonary disease. Pre-operative bronchoscopy findings were normal.
An excision of the tumour mass was undertaken in continuity with the upper part of the trachea. A window defect measuring 20 mm × 30 mm was excised. Surgical margins of all quadrants were evaluated by frozen section and found to be clear. Central compartment neck dissection and completion thyroidectomy were also undertaken. The defect was repaired with a composite nasal septal graft.
Histopathology revealed a 35 mm focus of papillary thyroid carcinoma, with probable lymphovascular invasion and focal squamous metaplasia. There was no frank invasion into cartilage. The surgical margins were clear.
The patient recovered well initially and was discharged 4 days post-operatively. On post-operative day 6, he returned with swelling around his wound due to subcutaneous emphysema and was re-admitted. He had no airway problems. The subcutaneous emphysema was managed conservatively with a hangman's compression dressing and resolved after 2 days. He was subsequently referred for radioiodine treatment.
At the time of writing, 18 months had passed following surgery. Follow-up MRI scans of the patient's neck and bronchoscopy have revealed no sign of cervical disease. His thyroglobulin levels were stable but elevated, at 100 µg/l. Follow-up serial CT imaging of the chest showed no progression in the pulmonary disease.
Case three
A 49-year-old female was referred for an opinion regarding further surgery following the intra-operative finding of tracheal invasion. She had undergone total thyroidectomy for a tall cell variant of papillary thyroid carcinoma that included resection of an involved right recurrent laryngeal nerve. The patient was obese with a short neck and a history of diabetes. The surgeon who performed the total thyroidectomy had noted focal involvement of the trachea. Radioiodine was administered post-operatively, but there was a lack of uptake in the thyroid bed. A subsequent bronchoscopy revealed erythema of the upper part of her trachea, but no mucosal irregularity.
The patient's management was discussed at the multidisciplinary head and neck clinic where it was recommended that conservative resection be undertaken followed by external beam radiation treatment. The patient was felt to be unsuitable for tracheal resection and re-anastomosis because of her obesity and the shortness of her neck. A total laryngectomy was discussed and the patient was informed that it may be required if her disease recurred.
Surgical exploration was undertaken and a window of abnormal trachea measuring 30 mm × 25 mm was excised, which included the lower part of her cricoid. The defect was repaired with a composite nasal septal graft harvested transnasally.
Histopathology revealed a tall cell variant of papillary thyroid carcinoma invading tracheal and cricoid cartilages. There was a positive surgical margin superiorly.
In view of the positive surgical margin status, further resection of cricoid cartilage was undertaken two months later when it was felt that the initial graft should be adequately healed. This was repaired with costal cartilage. Histopathology revealed that the disease extended to both the superior and lateral margins of the resected cartilage. The previous graft was observed bronchoscopically to have taken well, and viable cartilage was noted at the time of surgery (Figure 1).
Fig. 1 Bronchoscopic view of healed nasal septal graft reconstruction of tracheal defect (case three), two months post-operatively.
Post-operatively, the patient again recovered well and was discharged home. She has subsequently undergone external beam radiation (60 Gy in 30 fractions). She remains clinically free of disease. Her serum thyroglobulin level was 0.8 µg/l at two years following the completion of radiation treatment. Serial MRI scans and a follow-up bronchoscopy have not revealed any sign of disease recurrence.
Discussion
Invasion of the laryngotracheal complex is a major cause of morbidity and mortality in well-differentiated thyroid cancer. Complete surgical resection with preservation of function is the goal of treatment; however, the exact method of achieving this remains controversial.
McCaffrey proposed a staging system to classify the extent of local invasion in patients with well-differentiated thyroid cancer (Table I).Reference McCaffrey9 This system can be helpful in planning appropriate surgical resection. Patients with early stage I disease should be treated with total thyroidectomy, whilst those with more advanced stage IV and V disease are more likely to benefit from full segmental resection and reconstruction. There are sufficient data to suggest that those patients with stage II disease may be adequately treated with conservative shave resections; however, it can be difficult to accurately differentiate these patients from those with stage III disease, both pre- and intra-operatively. It is this group of patients with stage III disease who can potentially benefit from full thickness window resection.
Table I Staging system for invasive, well-differentiated thyroid carcinoma involving the aerodigestive tract*
*As proposed by McCaffrey.9
Proponents for a more conservative approach cite the advantages of good local control, good survival outcomes, and the avoidance of potential morbidities (associated with more extensive resections) that include recurrent laryngeal nerve palsy, aspiration and mortality. In addition, some patients may not be deemed suitable for sleeve resections in view of co-morbidities (e.g. obesity, previous radiation) and the perceived increased risk of anastomotic failure, which may be catastrophic. Indeed, the extent of morbidity associated with sleeve resections is not well documented in the literature.Reference Sywak, Pasieka, McFadden, Gelfand, Terrell and Dort10 However, any advantage gained by performing a conservative procedure needs to be tempered against the significant survival disadvantage that some residual macroscopic tumour may be left behind.Reference Honings, Stephen, Marres and Gaissert4, Reference Lipton, McCaffrey and van Heerden6, Reference McCaffrey9
Depth of invasion may be difficult to assess both pre-operatively (via imaging and direct visualisation with bronchoscopy) and intra-operatively, making delineation between stage II and III disease difficult.Reference Koike, Yamashita, Noguchi, Yamashita, Ohshima and Watanabe11 For example, a normal bronchoscopy may not exclude cartilage invasion. In addition, although MRI scanning is a reasonably good predictor of cartilage invasion, it lacks the resolution needed to identify the precise depth of invasion. Furthermore, well-differentiated thyroid cancer has a propensity to invade between the cartilaginous rings, and this component of the disease may be more difficult to safely extirpate with shave techniques.Reference Brennan, Bergstralh, van Heerden and McConahey1 Moreover, with this technique the adequacy of resection is difficult or impossible to assess via frozen section or paraffin section pathological examination.
The window tracheal resection technique has been advocated by some authors to deal with superficial invasion. It has the advantage of a full thickness resection that enables analysis of the adequacy of the excision with frozen sections. One of the limitations of this technique has in the past been the lack of adequate reconstructive options. The techniques previously described have included local soft tissue rotation flaps, such as the sternocleidomastoid rotation flap, and myofascial free flaps.Reference Friedman and Mayer12, Reference East, Grant and Jones13 These tissues differ vastly from cartilage, lacking both rigidity and mucosal lining. We believe the ideal reconstructive tissue for tracheal defects should retain rigidity to avoid dynamic airway collapse and enable rapid healing of the mucosal lining.
The composite nasal septal graft was initially described in a dog animal model.Reference Drettner and Lindholm14 In humans, it has been used in reconstruction in patients with benign and malignant disorders of the laryngotracheal airway. Zohar et al. described it as a means of reconstructing thyroid cartilage defects following partial laryngeal surgery for laryngeal carcinoma.Reference Zohar, Shvilli and Laurian15 It has also been used to reconstruct tracheal and cricoid defects in patients with subglottic or tracheal stenoses.Reference Krizek and Kirchner16, Reference Duncavage, Ossoff and Toohill17
Cansiz et al. reported on an extensive series of cases in which the composite nasal septal graft was used to reconstruct tracheal defects following the excision of primary tracheal tumours such as adenocarcinomas and invasive papillary thyroid carcinomas.Reference Cansiz, Yener, Bozkurt, Demir, Demirkaya and Sekercioglu18 The graft has been shown to be safe, with preservation of cartilage proven both radiologically and histologically.Reference Laurian, Zohar and Turani19, Reference Zohar, Hadar and Laurian20 Furthermore, the mucosal surface lining the trachea appears to heal well, without excessive granulation tissue formation.Reference Bozkurt and Cansiz21 This graft is readily available, has minimal donor site morbidity and provides the necessary rigidity required to reconstruct the trachea. In addition, the graft is lined with the same type of respiratory mucosa that lines the trachea, and, if aligned in a caudal or cephalad manner, may facilitate mucociliary clearance. Another benefit of this approach is the avoidance of a tracheotomy or free flap, which have been used in the past for patients undergoing laryngeal resections.Reference East, Grant and Jones13
• Invasion of the laryngotracheal complex by well-differentiated thyroid cancer is a major cause of morbidity and mortality
• Depth of invasion can be difficult to assess pre- and intra-operatively, making delineation between stage II and III disease difficult
• Window tracheal resection has the advantage of full thickness resection that enables assessment of excision adequacy with frozen section
• A composite nasal septal graft can be used to reconstruct a window tracheal defect in patients with well-differentiated thyroid cancer invading the trachea
• This can be used as an alternative to shaving
In our small series, there was no significant donor site or operative morbidity, apart from surgical emphysema, which resolved spontaneously. A minor epistaxis was treated conservatively two weeks post-operatively, but otherwise the nasal donor site healed well in all cases, without septal perforation. This technique was well tolerated. At the time of writing, all three patients remained free of disease, although one patient had positive surgical margins and required external beam radiation treatment. Nevertheless, the technique is limited by the size of the graft that can be safely harvested from the quadrangular septum. The largest graft we have harvested was 30 mm in diameter. Non-suction drains were used effectively in our patients (small air leaks around the graft are inevitable and preclude suction from being maintained).
Conclusion
We present three cases of well-differentiated thyroid cancer invading the trachea in which a composite nasal septal graft was utilised to reconstruct a window tracheal defect. This technique was demonstrated to be safe, and all three patients remained free of disease at the time of writing. We believe it may be a useful reconstructive option in patients with limited superficial invasion of the trachea, as an alternative to shaving.
