|Ahead of print
Long-term outcomes of differentiated thyroid cancers with tracheal invasion: A 15-year experience
Yogesh Tiwari, Arvind Krishnamurthy
Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
|Date of Submission||21-May-2019|
|Date of Decision||25-Jun-2019|
|Date of Acceptance||11-Apr-2019|
|Date of Web Publication||29-Jun-2020|
Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Background: Tracheal invasion is reported to occur in approximately one-third of the patients of locally advanced thyroid cancers. There is a paucity of data in literature with regard to the long-term outcomes of thyroid cancers with tracheal invasion.
Methods: A total of 37 patients from our tertiary care center underwent radical surgery for tracheal involvement for differentiated thyroid cancers between the years 2002 and 2016. The variables pertaining to the demographics, clinical presentation, imaging, operative details and histopathology reports were captured from the patient's case records and analyzed.
Results: Among the 37 patients, there were 21 males and 16 females. Majority of the patients (56.8%) were >55 years of age. Surgery (tracheal resection) was performed in the primary setting in 29 patients, whereas it was performed in a recurrent setting in 8 patients. As per the Shin classification, 3 patients belonged to Shin stage 1, 3 to Shin stage 2, 16 patients to Shin stage 3 and 15 patients to Shin stage 4. There was no 30 day postoperative mortality in our cohort. The median follow-up of our cohort was 175 months. The 5-, 10-, and the 15-year overall survivals of the entire cohort were 81.7%, 47.8%, and 35.9%, respectively.
Conclusion: Our series shows favorable long-term oncological outcomes of selected patients of thyroid cancers with tracheal resection and adds to the limited long-term data available in literature.
Keywords: Differentiated thyroid cancer, prognosis, tracheal invasion, tracheal reconstruction
| » Introduction|| |
The vast majority of patients with differentiated thyroid cancers (DTCs) tend to present with loco-regional disease and have excellent long-term outcomes. The adverse prognostic factors include age, tumor size, histology, extra-thyroidal extension and distant metastasis, with extra-thyroidal extension having the greatest negative impact on prognosis. Tracheal invasion is reported to occur in nearly one third of the patients of locally invasive thyroid cancers and is said to be the third most common site of local invasion following the strap muscles and the recurrent laryngeal nerve. Approximately 6% (ranging from 3.6% to 22.9%) of patients with DTC show tracheal invasion, further intraluminal extension is reported to occur in approximately 0.5%–1.5% of these patients., DTCs are typically indolent and surgical resection plays a critical role in its management. Advances in surgical techniques has allowed for radical surgery with extended tracheal resections and an array of reconstructive options for patients of DTCs with tracheal invasion. We present the long-term surgical (tracheal resection) results of our patients of DTCs with tracheal invasion.
| » Methods|| |
A total of 37 patients underwent surgery for tracheal involvement in thyroid cancers at our tertiary care center between the years 2002 and 2016. The variables pertaining to the demographics, clinical presentation, imaging, operative details and histopathology reports were captured from the patient's case records and were analyzed.
Patient selection and evaluation
A computed tomography (CT) scan of the neck with reconstruction [Figure 1] and [Figure 2] and a tracheoscopy was done to assess the extent of the tumor in all patients who presented either in view of suspicion of airway involvement (hoarseness of voice, stridor, or hemoptysis) or large size tumor with restricted mobility or retro-sternal extension. Tracheal resection was considered when complete resection of gross airway disease appeared feasible. Metastatic disease was not a contraindication for resection.
|Figure 1: Axial CT scan of the neck at the level of the thoracic inlet showing a thyroid cancer with tracheal infiltration (Shin 4)|
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|Figure 2: A CT scan with reconstruction (Virtual Bronchoscopy) showing the road map of the trachea-bronchial tree as well as the tracheal defect|
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Tracheal resection and reconstruction is a challenging operation for both the surgeon as well as the anesthesiologist, largely because the complex at times distorted anatomy of the airway itself. Distal tracheal intubation and intermittent positive pressure ventilation was used to achieve a good control of airway and adequate oxygenation in all our patients. A fiber-optic naso-tracheal awake intubation was performed if the tracheal invasion was deemed to be Shin 3 or 4 preoperatively. The fiber-optic bronchoscope was navigated past the involved tracheal segment to reach the distal normal trachea and the endotracheal tube was advanced over the bronchoscope.
Shaving, partial resection, or circumferential resection of the trachea was performed based on the Shin classification. Shave resection consisted of tangential excision of tumor with thyroid gland. Partial resections of the trachea were performed in patients of thyroid cancer with Shin 3 tumors and minimal tracheal involvement. Four patients additionally had tumors abutting the anterior portion of the cricoid cartilage. An eccentric primary closure was achieved in 8 patients. A window tracheostomy was fashioned in another patient with intent of a staged closure, but the patient refused the second surgery. The vast majority of the Shin III and all the Shin IV tumors underwent a circumferential resection with primary end to end anastomosis to maintain the airway patency. The ability to perform a well-vascularized tracheal anastomosis without any tension has vastly improved over the years with a better understanding of tracheal vascular anatomy and the performance of the laryngo-tracheal release procedures. Further simple maneuvers such as neck flexion and mediastinal dissection along the pretracheal region has aided in relieving the anastomotic tension. Most of the patients in our series needed an anterior pretracheal and a suprahyoid laryngeal (Montogomery) release. A thyrohyoid (Dedo) release was selectively performed if required. The membranous trachea was sutured in a continuous fashion, whereas the anterior trachea was sutured using interrupted 3-0 vicryl; care was taken to place the knots outside of the airway. The tracheal anastomosis is additionally covered by mobilization of the adjoining strap muscles. Surgical cross field intubation was carried out following tumor resection and all the patients were extubated at the conclusion of surgery after performing an on-table air leak test to check the integrity of the anastomosis [Figure 3]a and [Figure 3]b. A guardian stitch was placed from the skin of the submental crease to the anterior presternal skin in order to avoid hyperextension of the neck.
|Figure 3: (a) Intraoperative picture showing the performance of the tracheal anterior wall anastomosis with an endotracheal tube in situ. (b) Intraoperative picture of the leak test being performed, that is, flooding the operative field with saline and checking for air leak with positive pressure ventilation to check the integrity of the tracheal anastomosis|
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Central compartment neck dissection was done in all patients. Lateral neck dissection was done in case of clinico-radiologically or positive lateral neck node involvement on cytology. All patients were offered adjuvant high radioiodine therapy for ablation, that is, 80–100 milli-curie of iodine –131. Further external beam radiotherapy (60 Gray, conventional fractionation) was offered for all patients wherein the resection was deemed R2. The overall and event free survival (EFS) were calculated by using Kaplan-Meier method with log rank test using the Statistical Package for the Social Sciences (SPSS) software program, version 21.0.
| » Results|| |
Among the 37 patients, there were 21 males and 16 females. Majority of the patients (56.8%) were >55 years of age. Surgery (tracheal resection) was performed in the primary setting in 29 patients, whereas it was performed in a recurrent setting in 8 patients. However, the difference in the median survival of the patients operated in the primary setting and recurrent setting was 132 months and 153 months, respectively, which was not significant (P < 0.59). The demographic profile of our patient cohort is presented in [Table 1].
|Table 1: Demography of our patient cohort with thyroid carcinoma invading trachea|
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There was no 30-day postoperative mortality in our cohort. Ten patients (27%) harbored metastatic disease (seven had lung metastasis and three patients had bony metastasis); twenty-three patients (62%) presented with respiratory complaints such as hemoptysis, stridor, and breathing difficulty. Circumferential resection of the tracheal rings was performed in 23 patients, whereas partial tracheal ring removal was done in nine patients. In addition, five patients underwent tracheal shave resections. The resection was deemed R0 in 25 patients, whereas only an R1 and R2 resections was possible in nine and three patients, respectively. The R2 resections in the three patients were in view of soft-tissue disease in the tracheo-esophageal grove. Twenty-seven patients had a well differentiated histology, whereas 10 patients had high-risk histology. Twenty-one patients harbored positive neck nodes, the central group of node was positive in 19 patients, whereas the lateral group of nodes was positive in 11 patients. Nine patients harbored positive nodes in both the lateral and the central neck node groups, peri-nodal spread was noted in eight patients. As per Shin classification, 3 patients of Shin Stage 1, 3 patients of Shin Stage 2, 16 patients of Shin Stage 3, and 15 patients of Shin Stage 4. A median 4 tracheal rings (range between 1 and 7 rings) were removed to ensure complete resection.
Five patients had subcutaneous emphysema that was managed conservatively. Postoperatively three patients developed tracheomalacia necessitating a re-intubation and all of whom was managed conservatively. Re-exploration was done in three patients (one for anastomotic leak and two patients for hemorrhage). One patient had aspiration for liquids, which was managed conservatively. The complications are captured in [Table 2]. Adjuvant radioiodine therapy was advised in all patients; however, three patients did not receive the same. Further adjuvant external beam radiotherapy was advised in the three patients who underwent an R2 resection; however, one patient refused. This however did not have a bearing on the outcomes.
The median follow-up of our cohort was 175 months. The 5-, 10-, and the 15-year EFS was 37.6%, 17.6%, and 12.8%, respectively, whereas the 5-, 10,- and the 15-year overall survivals (OS) of the entire cohort were 81.7%, 47.8%, and 35.9%, respectively. Two patients had local recurrence (5.4%) and eight patients had regional recurrence (21.6%). One patient had intraluminal recurrence (2.7%). Four patients had distant recurrence (14.2%). The mean OS was 80 months and 135 months, respectively, in patients presenting with metastatic versus nonmetastatic disease (P < 0.015); however, this difference was not significant between stages 1 and 2 (P < 0.165) as compared to stages 3 and 4 (P < 0.031). Further, there was no difference in survival for tracheal resections done in the primary setting versus those done in the recurrent setting, provided an R0 resection could be achieved (P < 0.59). Our study further showed that patients with lateral neck node positivity had a statistically higher chance of developing loco-regional recurrences (P < 0.034). The various factors studied as possible determinant of patient outcomes has been captured in [Table 3]. A comparative comparison with the other case series is shown in [Table 4].
|Table 3: Study of the factors predicting the overall survival (OS) and event free survival (EFS)|
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|Table 4: Comparisons of postoperative complications in different studies in carcinoma thyroid invading trachea|
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| » Discussion|| |
The thyroid gland is located in close proximity of many critical structures in the neck. Shin et al., in a landmark paper in the year 1993, described the various routes of tracheal invasion from a well DTC. They showed that the collagen fibers of the thyroid gland capsule in the posterior aspect coursed into the inter cartilaginous spaces of the trachea, which on further histology revealed neurovascular bundles and lymphatics coursing perpendicular to the trachea. The anatomical proximity of the thyroid gland to the anterior tracheal wall and the above mentioned neurovascular and lymphatic channels can help explain why the anterior route is a more common route of tracheal invasion. The authors further described the five stages of tracheal invasion: stage 0 for tumors with no extra-thyroidal extension, stage I for extra-thyroidal disease abutting the airway, stage II for invasion of the tracheal cartilage rings, stage III for tumors that involves the tracheal submucosa, and stage IV for tumor that involves the tracheal mucosa.
DTCs are typically indolent and surgical resection plays a critical role in its management. However, the extent of surgery for locally advanced thyroid cancers has been a source of controversy and this is primarily fueled by the lack of prospective studies. The latest American Thyroid Association (ATA-2015) management guidelines state that the surgical decision-making for management of tumors invading the aerodigestive tract is complex and should balance oncologic surgical completeness with preservation of the function of the upper aerodigestive tract. Almost all authors agree that a gross intra luminal tumor should be completely resected because an incomplete resection results in a poor prognosis and is unacceptable. There is, however, very little consensus with regard to the management for superficial invasion (Shins 1 and 2) that does not involve the luminal surfaces of the aerodigestive tract. Although some groups have advocated aggressive circumferential resections, other groups have shown that in patients with tumors abutting the tracheal cartilage but without the involvement of the submucosa, less-aggressive tracheal resections can result in comparable oncologic outcomes while decreasing postoperative morbidity.,,,,,,,,,, Majority of the patients (62%) in our series underwent circumferential tracheal resections. Several reconstructive methods have been reported, depending on the size of the tracheal defect. In instances of tracheal defects lesser than half the circumference of the trachea, soft tissue reconstruction alone is enough to maintain the size of the lumen. For cases in which defects involve, the entire tracheal circumference, end-to-end anastomosis has been considered gold standard.
Tracheal resections and reconstructions can be safely performed in the vast majority of the carefully selected patients. However, such surgeries are not without its due share of complications, which have been reported in approximately one-fifth of the patients. The critical considerations for a safe tracheal resection include preservation of the tracheal blood supply and at least one functioning recurrent laryngeal nerve apart from a tension free anastomosis. The various complications include laryngeal edema, anastomotic leaks, wound infection, and airway dysfunction. The late complications include granuloma formation, restenosis, trachea-esophageal fistulas and trachea innominate fistulas. Anastomotic dehiscence was the most dreaded complication of tracheal resections as was noted in a case series of 69 patients, where in the reported morbidity and mortality rates were 36% and 12% respectively. In our study, the rate of anastomotic dehiscence rate was 0.03% [Table 5].
One of the important factors to prevent anastomotic dehiscence is tension free anastomosis., Some authors claim that tracheal defects of approximately 5–6 cm can be safely resected and primarily anastomosed. A supra-laryngeal release and a suprahyoid muscle release can add several centimeters as deemed necessary so as to enable a safe end-to-end anastomosis. In addition, several additional centimeters can be gained by the performance of a sternotomy, hilar mobilization, and reimplantation of the left main-stem bronchus to the bronchus intermedius. Fortunately, such procedures are rarely required. Several authors have advocated the maintenance of the “chin to chest position” by placing two stitches in submental crease.,, An critical factor to prevent anastomotic leak is to preserve the tracheal blood supply that primarily originates from inferior thyroid artery and passes lateral along the lateral walls of trachea; hence, it is advisable to dissect the trachea preferably along the anterior wall and not to dissect beyond 1 cm from the residual stump to be anastomosed. All patients in our study were extubated following the completion of surgery; however, three patients had to be re-intubated as they developed tracheomalacia in the postoperative period. There is no consensus in literature with regard to the timing of extubation.,,
It is generally agreed that the maximum length of tracheal resection that can be managed with primary anastomosis is approximately 6 cm, representing approximately half of the length of the trachea. Autologous composite neo-trachea has been the best surgical solution for extended tracheal replacement, considering the fact that synthetic prosthesis did not achieve satisfactory outcomes with a high risk of life-threatening airway hemorrhage due to vascular erosions. The other options include tracheal transplantation, conduit allografts, and bioengineered tracheal replacements, but each of these options has technical issues and has not yielded reliable long-term outcomes.
The 5-, 10-, and the 15-years OSs of the entire cohort were 81.7%, 47.8%, and 35.9%, respectively, whereas the 5-year survival rate in the case series by Tsai et al. and Ishihara et al. was 78% and 88%, respectively. The risk of postoperative morbidity and mortality can be reduced by performing such complex surgical procedures in high volume centers.,,, The postoperative mortality and postoperative morbidity in our series were 0% and 18.9%, respectively. The 5-year median loco-regional recurrence rate in our series was 39 months. There is considerable variation in literature with regard to the factors associated with loco-regional recurrence in patients of thyroid cancer with tracheal invasion.,,,, Our study showed that patients with lateral neck node positivity had a statistically higher chance of developing loco-regional recurrences. This observation was also noted in the case series by Kim et al. No other factor seemed to have any bearing on the outcomes of the patients in our series.
Our series has a few limitations primarily due to its retrospective design and with modest numbers recruited over a long period of 15 years. Moreover, only patients considered for a tracheal resection were included. Targeted therapies using tyrosine kinase inhibitors are presently available for management of rapidly progressive distant disease; however, none of our patients were administered the same. Despite these limitations, our data does show that patients with locally advanced thyroid cancers can have reasonably good long-term outcomes when managed at a high-volume center with a dedicated multidisciplinary team. Our series further shows that radical tracheal surgeries can be offered to patients with high-risk histology, in the recurrent setting as well as for selected patients with metastatic disease.
| » Conclusion|| |
In conclusion, our study clearly shows the long-term favorable oncological outcomes of tracheal resection in our cohort of patients of thyroid cancer. Radical surgery with an aim of achieving negative margins remains the mainstay of management for all patients with locally advanced thyroid cancer including those with tracheal invasion. Adjuvant therapies with radioiodine and external beam radiotherapy should not be expected to compensate for an incomplete surgical resection. Appropriate patient selection and involvement of a multidisciplinary team are critical to ensure the best outcomes in this complex group of patients. Our series of tracheal resections with 15-year outcome results thus adds to the limited long-term data available in literature.
Ethical policy and institutional review board statement
All procedures performed in this case report were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]