Ann Surg Oncol DOI 10.1245/s10434-015-4492-5
ORIGINAL ARTICLE – HEAD AND NECK ONCOLOGY
Surgical Management of Cricotracheal Invasion by Papillary Thyroid Carcinoma Sueyoshi Moritani, MD Center for Head and Neck Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan
ABSTRACT Background. In general, patients with papillary thyroid carcinoma (PTC) have an excellent postoperative prognosis. Those with cricoid and/or tracheal PTC invasion, however, are at a higher risk of postoperative morbidity and airway insufficiency. Methods. We investigated postoperative airway outcomes, locoregional recurrence, and survival rates in patients with PTC who underwent cricotracheal resection. The records of PTC patients who underwent surgery at our institution between 1981 and 2009 were reviewed retrospectively, and 110 patients with cricotracheal invasion were enrolled. Curative resection was performed in all patients, and cricotracheal function was preserved or reconstructed when possible. Results. Of the 110 patients, 57 and 53 patients had superficial and intraluminal invasion of the larynx, respectively. After the initial surgery, the 10-year diseasespecific survival rates were 90.8 and 44.4 % in patients with superficial and intraluminal invasion of the cricotracheal area, respectively. Only six patients (5.5 %) had an isolated upper aerodigestive tract recurrence. Five patients were managed with an additional window resection as salvage surgery. Consequently, only one patient (0.9 %) underwent total laryngectomy. Altogether, 31 patients (28.0 %) had a permanent stoma, 9 and 15 of which were caused by cricotracheal invasion and invasion of other aerodigestive structures, respectively. Conclusions. Window resection for intraluminal cricotracheal invasion by PTC produced good surgical outcomes that resulted in a low local recurrence rate and survival rates that resembled those associated with other surgical
Ó Society of Surgical Oncology 2015 First Received: 24 October 2014 S. Moritani, MD e-mail: [email protected]
treatments. Treatment of multiple organ invasion of the aerodigestive tract was necessary to improve postoperative functional outcomes in these patients.
Papillary thyroid carcinoma (PTC) generally has an excellent prognosis. However, when it invades the upper aerodigestive tract, although a rare occurrence, it affects both prognosis and quality of life. Cricoid and/or tracheal invasion occurs in approximately 6.0 % (3.6–22.9 %) of patients with PTC.1,2 Also, intraluminal extension occurs in 0.5–1.5 % of PTC patients.3 Cricoid and/or tracheal invasion is an independent negative prognostic factor for survival, and patients with intraluminal extension have a worse prognosis than those with superficial tracheal invasion.4–7 Invasion of the aerodigestive tract produces several symptoms, the most common of which is hoarseness caused by invasion of the recurrent laryngeal nerve (RLN), Advanced invasion produces hemoptysis, stridor, dyspnea, and airway hemorrhage. Whereas patients with superficial invasion of the aerodigestive tract show no symptoms, hemoptysis, stridor, dyspnea, and airway hemorrhage are associated with intraluminal invasion. Among patients with invasion of the aerodigestive tract, the quality of life greatly deteriorates with advanced invasion and organ defects resulting from tumor resection. The therapeutic dilemma is whether one should perform radical tumor resection to reduce the chance of local recurrence or a conservative limited resection, thereby preserving the upper airway tract. Surgical management of airway invasion has therefore remained controversial. Although a grossly evident intraluminal tumor should be resected completely (because incomplete resection results in a poor prognosis8), there is no consensus about the type of surgical management that should be adopted for superficial invasion that does not involve the intraluminal surfaces of the aerodigestive tract. In other words, the
S. Moritani
choice between shave excision and radical tumor resection remains unclear. There is also no consensus regarding the comparative effectiveness of window resection and circumferential resection as surgical treatments for patients with intraluminal cricotracheal invasion. Our therapeutic strategy for patients who have PTC with cricotracheal invasion was to perform shave excision for superficial invasion and window resection for intraluminal invasion. Under this strategy, window resection was used as a means of preserving as much of the normal tissue adjacent to the tumor as possible and still improve functional outcomes. The purpose of this study was to investigate locoregional recurrence and survival rates in patients who underwent cricotracheal resection for PTC at our institution. We also sought to examine the postoperative airway outcomes in these patients. METHODS We retrospectively reviewed the medical records of patients with PTC who were treated surgically at Kyoto Medical Center and Kusatsu General Hospital between 1981 and 2009. The patients who had cricotracheal invasion by PTC were selected for this study. Cricoid cartilage, the ring-like cartilage of the larynx, helps maintain the laryngeal framework and plays small roles in laryngeal functions, such as speaking and swallowing. Laryngeal function can be compromised by tumor invasion into the cricoarytenoid joint. Thus, it is believed that both cricoid cartilage and tracheal invasion can be identified based on the maintenance of the laryngotracheal framework. Data were collected on patients with cricotracheal invasion, with the exception of those with thyroid cartilage invasion or intraluminal invasion of the glottis or supraglottic portion of the larynx. The relevant institutional review board approved this study. Patient confidentiality was maintained, and informed consent was obtained from all patients. Computed tomography (CT) or magnetic resonance imaging (MRI) and endoscopic examination were used for preoperative evaluation. Intraluminal cricotracheal invasion was evaluated by endoscopic examination. In cases of suspected esophageal invasion, gastrointestinal fiberscopy was performed preoperatively. The cricotracheal invasion was evaluated by CT or MRI. Gross invasion or pathological angiogenesis of the cricoid and trachea was evaluated endoscopically. Preoperative examinations included evaluation of the invasion depth from the cricotracheal cartilage to the cricotracheal lumen. The depths of tumor invasion were classified into two
categories: invasion up to the inner cricotracheal cartilage and intraluminal invasion. Superficial invasion of the cricoid and trachea was defined as cricotracheal invasion up to the inner cricotracheal cartilage based on the results of preoperative and intraoperative evaluations or an intraoperative cryosection analysis. Intraluminal cricotracheal invasion was defined as invasion of the lining of the cricoid and trachea (as assessed using CT or MRI), gross invasion, or pathological angiogenesis of the cricoid and trachea (as assessed by endoscopic examination). PTC invasion into other organs was also examined. The surgical treatment for cricotracheal invasion consisted of shave excision for cases of superficial invasion and window resection for cases of intraluminal invasion. Shave excision was defined as sharp separation of the superficially invading tumor from the cricotracheal cartilage. This surgical method was performed when tumor infiltration did not reach the cricotracheal lumen and was adapted for superficial invasion of the cricoid and trachea. Window resection was defined as resection of the cartilage, including the penetrated area of the cricotracheal lumen. Normal tissue of the cricoid and trachea was retained to the greatest extent possible to allow reconstruction of the cricotracheal defect. Circumferential sleeve resection was adapted for massive cricotracheal infiltration. Curative resection was defined as margin-negative tumor resection, confirmed based on the intraoperative pathological diagnosis. Curative resection was performed for all PTC patients with invasive extrathyroidal extension. The aerodigestive function was preserved or reconstructed when possible. Curative resection was aided by the use of an operating microscope when necessary. During surgery, multiple margin samples were collected for frozen section analyses to confirm margin negativity pathologically. In patients with positive margins, additional resection was performed until a negative margin was achieved. Intraoperative cryosection analysis was performed to preserve the greatest possible extent of normal tissue adjacent to the tumor, as well as to improve functional outcomes. Surgical management was adapted for cricotracheal involvement. Postoperative assessments with cross-sectional imaging and endoscopic examination were performed every 6 months to detect recurrence. Functional outcome was evaluated in terms of the stomal closure rate. (Stomal closure reflects the absence of airway stenosis and aspiration.) Cricotracheal defects are the result of cricotracheal stomata that do not close immediately. Our surgical management of cricotracheal defects consisted of staged operations for stomal closure or reconstruction. Small cricotracheal stomata were closed using a local cutaneous
Management of Cricotracheal Invasion by PTC TABLE 1 Baseline patient characteristics Characteristic
Initial treatment (n = 81)
Treatment for recurrence (n = 29)
Age (years), mean (SD)
61 (15)
64 (10)
Male
21 (26 %)
7 (24 %)
Female
60 (74 %)
22 (76 %)
Sex
Presentation Good
75 (93 %)
25 (86 %)
Poor
6 (7 %)
4 (14 %)
Superficial invasion
51 (63 %)
6 (21 %)
Intraluminal invasion
30 (27 %)
23 (79 %)
Prior distant metastasis, cricotracheal invasion
9 (11 %)
7 (24 %)
Cricotracheal invasiona
a
The presence of intraluminal cricotracheal invasion differed significantly between the initial treatment group and the recurrence treatment group (v2 test, p = 0.0001)
TABLE 2 Locoregional and distant recurrences in patients with cricotracheal PTC invasion Operation
No.
Locoregional recurrence
Aerodigestive recurrence
Distant recurrence
Shave excision
57
6 (11 %)
3 (5 %)
5 (9 %)
Window resection
53
8 (15 %)
3 (6 %)
14 (26 %)
TABLE 3 Stoma status in patients with cricotracheal PTC invasion Operation
No.
No stoma or a temporary stoma
Permanent stoma
Shave excision
57
57 (100 %)
0
Window resection
53
22 (42 %)
31 (58 %)
flap. The original deltopectoral (D-P) flap was used to repair large cricotracheal defects that could not be closed with a local flap but in which the remaining hard structure could still provide internal support. Large cricotracheal defects without this internal support were closed using the D-P flap combined with nasal septal cartilage for hard structure reconstruction. Finally, cricotracheoplasty was performed using the D-P flap to improve phonetic function in patients with a large cricotracheal defect that could not be closed. The Mann–Whitney test was used to compare variables. The 10-year DSS rates were estimated using the Kaplan– Meier method and compared using the log-rank test. Results were considered significant for values of p \ 0.05. Commercially available software (Ekuseru-Toukei 2012; SSRI, Tokyo, Japan) was used for the statistical analyses. RESULTS During the study period, 110 of the 746 PTC patients had cricotracheal invasion. Among the 110 patients enrolled, 61 had tracheal invasion, 44 had cricotracheal
invasion, and 5 had cricoid invasion. The study cohort included 27 men (24.5 %) and 83 women (75.5 %). In all, 81 patients were found to have cricotracheal invasion by PTC at the time of the initial diagnosis, whereas 29 patients were diagnosed with cricotracheal invasion by PTC at cancer relapse. Of the 110 patients, 89 (80.9 %) had been referred from other institutions for surgery to treat cricotracheal invasion by PTC. The mean age of the patients at the time of surgery for laryngeal invasion was 62 years (range 27–92 years). The duration of follow-up after surgery was 7.4 ± 6.3 years (mean ± standard deviation) for patients who survived the procedure. Baseline characteristics did not differ significantly between patients who received initial treatment and those who were treated for recurrence, with the exception of the degree of cricotracheal invasion (Table 1). Altogether, 57 patients with superficial invasion underwent shave excision, and 53 patients with intraluminal invasion underwent window resection. Of the latter 53 patients, only 2 underwent circumferential sleeve resection. In all, 14 and 19 patients had locoregional disease and distal recurrence, respectively. The lesion was located on
S. Moritani
1.0
DSS ratio
0.8 0.6 0.4 0.2 0.0 0
1000
2000
3000
4000
Days after surgery
FIG. 1 Comparison of disease-specific survival (DSS) rates for patients who received initial surgery with superficial and intraluminal invasion of the cricoid-trachea
the upper aerodigestive tract in 6 of the 14 patients with locoregional recurrence. Among these six patients, two had a lesion on the laryngoesophagus, two had a lesion on the cricoid cartilage, one had a lesion on the cricotracheal area, and one had a lesion on the trachea (5.5 %) (Table 2). They were managed with total laryngectomy and an additional window resection as salvage surgery. As a result, only one patient (0.9 %) underwent total laryngectomy. Among the 81 patients who underwent initial surgery, those who had intraluminal cricotracheal invasion had a significantly lower 10-year DSS rate than those who underwent surgery for superficial cricotracheal invasion (44.4 vs. 90.8 %, respectively) (Fig. 1). Functional outcomes were examined in terms of the stomal closure rates. Permanent stomata were present in 31 patients (28 %) with intraluminal invasion (Table 3). The permanent stomata were caused by cricotracheal invasionassociated large cricotracheal defects in 9 patients, bilateral RLN invasion in 11 patients, continuous aspiration without pulmonary complications in 7 patients (window resection and esophageal reconstruction for cricotracheal-esophageal invasion in 4, age-associated depressed swallowing function in 2, depressed swallowing function caused by brain
metastasis in 1), and postoperative early death of 4 patients (acute respiratory distress syndrome caused by respiratory insufficiency from bilateral phrenic nerve invasion in 1, intestinal bleeding in 1, heart failure in 1, and injury to the innominate artery requiring a resected clavicle for mediastinal dissection in 1). Of the 11 patients with bilateral RLN invasion, 5 had had bilateral vocal cord paralysis preoperatively, and 6 had had ipsilateral vocal cord paralysis at a prior surgery and contralateral RLN invasion found at the surgery performed for cricotracheal invasion. Among the 110 patients (71 %) with cricotracheal invasion, 78 also had PTC invasion into other aerodigestive tract structures, including the esophagus (n = 46) and the RLN (n = 71). Among these 78 patients, 39 had invasion of both the esophagus and the RLN, and 39 had only one structure invaded (either the esophagus or the RLN). Permanent stomata occurred more frequently in patients with RLN invasion than in those with esophageal invasion (Table 4). DISCUSSION We found that window resection for intraluminal cricotracheal invasion by PTC produced good outcomes, resulting in a low rate of local recurrence and a survival rate that resembled that after other surgical treatments. However, cricotracheal invasion was accompanied by invasion of other aerodigestive structures in many patients. Thus, treatment of multiple organ invasion of the aerodigestive tract was necessary to improve the postoperative functional outcomes in these patients. Although PTC generally has an excellent prognosis, the rare invasions of the upper aerodigestive tract by PTC have negative effects on prognosis and quality of life. Cricotracheal invasion is an independent negative prognostic factor for survival, and patients with intraluminal extension have a worse prognosis than those with superficial tracheal invasion. The surgical management of airway invasion remains controversial. There is no consensus on the surgical management that should be used (shave excision or
TABLE 4 Stoma status according to the presence or absence of invaded aerodigestive tract structures in patients with cricotracheal invasion Esophageal invasion (n = 110)
RLN invasion (n = 71)a
No stoma or a temporary stoma (n = 79)
Permanent stoma (n = 31)
Yes (n = 46)
(?) 39
25
14
(-) 7
4
3
(?) 32 (-) 32
18 32
14 0
No (n = 64)
RLN recurrent laryngeal nerve, (?) yes, (-) no a
Permanent stoma occurred more frequently in patients with RLN invasion than in those with esophageal invasion (v2, p = 0.0004)
Management of Cricotracheal Invasion by PTC
radical tumor resection) for superficial invasion of the aerodigestive tract. Because it has been shown that shave excision and radical tumor resection produce similar survival rates, it has been suggested that shave excision should be adequate for minimal invasion of the aerodigestive tract in cases in which there is no grossly evident residual tumor.7,9–12 However, it has also been shown that radical tumor resection reduces the chance of local recurrence and improves the postoperative prognosis when compared with shave excision, which has led other researchers to suggest that radical tumor resection is appropriate even for minimal invasion of the aerodigestive tract.1,2,13 There is also no consensus regarding the comparative effectiveness of window resection and circumferential resection as surgical treatments for patients with cricotracheal invasion. It has been reported that the latter should be used for patients with invasion of the trachea by thyroid carcinoma because histological examinations of the circumferential spread showed that invasion on the mucosal side exceeded invasion on the adventitial side.14 Also, suture closure of a window defect is rarely possible. Given the safety of circumferential tracheal resection, there is no clinical role for window resection.3 Shave excision and window resection in this study were associated with 10-year DSS rates of 90.8 and 44.4 %, respectively (p \ 0.0001). Intraluminal extension into the airway was associated with worse survival than superficial invasion of the airway, as has also been noted in previous reports.5–7 However, many of the fatal cases were caused by distant metastases. Only one patient died because of locoregional recurrence. The rate of locoregional recurrence in the upper aerodigestive tract was 5.5 %. These results were equal to or better than the results reported in several previous studies.2,12,15 Only one of the six patients with aerodigestive tract recurrence in our study had to be managed with total laryngectomy. The others were treated successfully with an additional shave excision or sleeve window resection. The rate of total laryngectomy for laryngotracheal invasion was lower in this study than in previous reports.16,17 A closed stoma affects functional outcomes, including postoperative breathing, phonetics, and swallowing. Permanent stomata were present in 31 patients with intraluminal invasion. Nine patients (8.2 %) had permanent stomata caused by large cricotracheal defects that were associated with cricotracheal invasion. These patients had defects that exceeded the semicircular area at the cricoidtrachea connection. Explanations for the poor functional outcome included concurrent cricotracheal invasion by PTC and invasion of other aerodigestive structures, such as the RLN and/or esophagus. Permanent stoma occurred more frequently in patients with RLN invasion than in those with esophageal invasion.
Postsurgical external-beam radiation therapy was not indicated for patients with cricotracheal invasion. Unfortunately, distant metastasis occurred frequently, even in patients with good locoregional control, and became a leading cause of death. We attributed the low rate of locoregional recurrence to the surgical approach adopted, wherein pathologically negative margins were confirmed by frozen section analysis to reduce the risk of incomplete resection and to preserve as much adjacent healthy tissue as possible. Therefore, to ensure successful resection, margin negativity should be confirmed intraoperatively using cryosection analysis. CONCLUSIONS Window resection for cricotracheal invasion by PTC produced good outcomes, resulting in a low rate of local recurrence and survival rates that resembled those reported after other surgical treatments. In many patients, however, cricotracheal invasion was accompanied by invasion of other aerodigestive structures. Treatment of multiple organ invasion of the aerodigestive tract was thus necessary to improve postoperative functional outcomes in these patients.
REFERENCES 1. Park CS, Suh KW, Min JS. Cartilage-shaving procedure for the control of tracheal cartilage invasion by thyroid carcinoma. Head Neck. 1993;15:289–91. 2. 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. 3. Honings J, Stephen AE, Marres HA, Gasser HA. The management of thyroid carcinoma invading the larynx or trachea. Laryngoscope. 2010;120:682–9. 4. McCaffrey TV, Bergstralh EJ, Hay ID. Locally invasive papillary thyroid carcinoma: 1940–1990. Head Neck. 1994;16:165–72. 5. McCaffrey JC. Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology. Laryngoscope. 2006;116:1–11. 6. Hotomi M, Sugitani I, Toda K, Kawabata K, Fujimoto Y. A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis. World J Surg. 2012;36:1231–40. 7. Wada N, Nakayama H, Masudo Y, Suganuma N, Rino Y. Clinical outcome of different modes of resection in papillary thyroid carcinomas with laryngotracheal invasion. Langenbecks Arch Surg. 2006;391:545–9. 8. Bayles SW, Kingdom TT, Carlson GW. Management of thyroid carcinoma invading the aerodigestive tract. Laryngoscope. 1998;108:1402–7. 9. Czaja JM, McCaffrey TV. The surgical management of laryngotracheal invasion by well–differentiated papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 1997;123:484–90. 10. Kowalski LP, Filho JG. Results of the treatment of locally invasive thyroid carcinoma. Head Neck. 2002;24:340–4.
S. Moritani 11. Tsukahara K, Sugitani I, Kawabata K. Surgical management of tracheal shaving for papillary thyroid carcinoma with tracheal invasion. Acta Otolaryngol. 2009;129:1498–502. 12. Ito Y, Fukushima M, Yabuta T, et al. Local prognosis of patients with papillary thyroid carcinoma who were intra-operatively diagnosed as having minimal invasion of the trachea: a 17-year experience in a single institute. Asian J Surg. 2009;32:102–8. 13. Tsai YF, Tseng YL, Wu MH, Hung CJ, Lai WW, Lin MY. Aggressive resection of the airway invaded by thyroid carcinoma. Br J Surg. 2005;92:1382–7. 14. Ozaki O, Sugino K, Mimura T, Ito K. Surgery for patients with thyroid carcinoma invading the trachea: circumferential sleeve
resection followed by end-to-end anastomosis. Surgery. 1995;117:268–71. 15. McCarty TM, Kuhn JA, Williams WL Jr, et al. Surgical management of thyroid cancer invading the airway. Ann Surg Oncol. 1997;4:403–8. 16. Gaissert HA, Honings J, Grillo HC, et al. Segmental laryngotracheal and tracheal resection for invasive thyroid carcinoma. Ann Thorac Surg. 2007;83:1952–9. 17. Nakao K, Kurozumi K, Nakahara M, Kido T. Resection and reconstruction of the airway in patients with advanced thyroid cancer. World J Surg. 2004;28:1204–6.
ORIGINAL ARTICLE – HEAD AND NECK ONCOLOGY
Surgical Management of Cricotracheal Invasion by Papillary Thyroid Carcinoma Sueyoshi Moritani, MD Center for Head and Neck Surgery, Kusatsu General Hospital, Kusatsu, Shiga, Japan
ABSTRACT Background. In general, patients with papillary thyroid carcinoma (PTC) have an excellent postoperative prognosis. Those with cricoid and/or tracheal PTC invasion, however, are at a higher risk of postoperative morbidity and airway insufficiency. Methods. We investigated postoperative airway outcomes, locoregional recurrence, and survival rates in patients with PTC who underwent cricotracheal resection. The records of PTC patients who underwent surgery at our institution between 1981 and 2009 were reviewed retrospectively, and 110 patients with cricotracheal invasion were enrolled. Curative resection was performed in all patients, and cricotracheal function was preserved or reconstructed when possible. Results. Of the 110 patients, 57 and 53 patients had superficial and intraluminal invasion of the larynx, respectively. After the initial surgery, the 10-year diseasespecific survival rates were 90.8 and 44.4 % in patients with superficial and intraluminal invasion of the cricotracheal area, respectively. Only six patients (5.5 %) had an isolated upper aerodigestive tract recurrence. Five patients were managed with an additional window resection as salvage surgery. Consequently, only one patient (0.9 %) underwent total laryngectomy. Altogether, 31 patients (28.0 %) had a permanent stoma, 9 and 15 of which were caused by cricotracheal invasion and invasion of other aerodigestive structures, respectively. Conclusions. Window resection for intraluminal cricotracheal invasion by PTC produced good surgical outcomes that resulted in a low local recurrence rate and survival rates that resembled those associated with other surgical
Ó Society of Surgical Oncology 2015 First Received: 24 October 2014 S. Moritani, MD e-mail: [email protected]
treatments. Treatment of multiple organ invasion of the aerodigestive tract was necessary to improve postoperative functional outcomes in these patients.
Papillary thyroid carcinoma (PTC) generally has an excellent prognosis. However, when it invades the upper aerodigestive tract, although a rare occurrence, it affects both prognosis and quality of life. Cricoid and/or tracheal invasion occurs in approximately 6.0 % (3.6–22.9 %) of patients with PTC.1,2 Also, intraluminal extension occurs in 0.5–1.5 % of PTC patients.3 Cricoid and/or tracheal invasion is an independent negative prognostic factor for survival, and patients with intraluminal extension have a worse prognosis than those with superficial tracheal invasion.4–7 Invasion of the aerodigestive tract produces several symptoms, the most common of which is hoarseness caused by invasion of the recurrent laryngeal nerve (RLN), Advanced invasion produces hemoptysis, stridor, dyspnea, and airway hemorrhage. Whereas patients with superficial invasion of the aerodigestive tract show no symptoms, hemoptysis, stridor, dyspnea, and airway hemorrhage are associated with intraluminal invasion. Among patients with invasion of the aerodigestive tract, the quality of life greatly deteriorates with advanced invasion and organ defects resulting from tumor resection. The therapeutic dilemma is whether one should perform radical tumor resection to reduce the chance of local recurrence or a conservative limited resection, thereby preserving the upper airway tract. Surgical management of airway invasion has therefore remained controversial. Although a grossly evident intraluminal tumor should be resected completely (because incomplete resection results in a poor prognosis8), there is no consensus about the type of surgical management that should be adopted for superficial invasion that does not involve the intraluminal surfaces of the aerodigestive tract. In other words, the
S. Moritani
choice between shave excision and radical tumor resection remains unclear. There is also no consensus regarding the comparative effectiveness of window resection and circumferential resection as surgical treatments for patients with intraluminal cricotracheal invasion. Our therapeutic strategy for patients who have PTC with cricotracheal invasion was to perform shave excision for superficial invasion and window resection for intraluminal invasion. Under this strategy, window resection was used as a means of preserving as much of the normal tissue adjacent to the tumor as possible and still improve functional outcomes. The purpose of this study was to investigate locoregional recurrence and survival rates in patients who underwent cricotracheal resection for PTC at our institution. We also sought to examine the postoperative airway outcomes in these patients. METHODS We retrospectively reviewed the medical records of patients with PTC who were treated surgically at Kyoto Medical Center and Kusatsu General Hospital between 1981 and 2009. The patients who had cricotracheal invasion by PTC were selected for this study. Cricoid cartilage, the ring-like cartilage of the larynx, helps maintain the laryngeal framework and plays small roles in laryngeal functions, such as speaking and swallowing. Laryngeal function can be compromised by tumor invasion into the cricoarytenoid joint. Thus, it is believed that both cricoid cartilage and tracheal invasion can be identified based on the maintenance of the laryngotracheal framework. Data were collected on patients with cricotracheal invasion, with the exception of those with thyroid cartilage invasion or intraluminal invasion of the glottis or supraglottic portion of the larynx. The relevant institutional review board approved this study. Patient confidentiality was maintained, and informed consent was obtained from all patients. Computed tomography (CT) or magnetic resonance imaging (MRI) and endoscopic examination were used for preoperative evaluation. Intraluminal cricotracheal invasion was evaluated by endoscopic examination. In cases of suspected esophageal invasion, gastrointestinal fiberscopy was performed preoperatively. The cricotracheal invasion was evaluated by CT or MRI. Gross invasion or pathological angiogenesis of the cricoid and trachea was evaluated endoscopically. Preoperative examinations included evaluation of the invasion depth from the cricotracheal cartilage to the cricotracheal lumen. The depths of tumor invasion were classified into two
categories: invasion up to the inner cricotracheal cartilage and intraluminal invasion. Superficial invasion of the cricoid and trachea was defined as cricotracheal invasion up to the inner cricotracheal cartilage based on the results of preoperative and intraoperative evaluations or an intraoperative cryosection analysis. Intraluminal cricotracheal invasion was defined as invasion of the lining of the cricoid and trachea (as assessed using CT or MRI), gross invasion, or pathological angiogenesis of the cricoid and trachea (as assessed by endoscopic examination). PTC invasion into other organs was also examined. The surgical treatment for cricotracheal invasion consisted of shave excision for cases of superficial invasion and window resection for cases of intraluminal invasion. Shave excision was defined as sharp separation of the superficially invading tumor from the cricotracheal cartilage. This surgical method was performed when tumor infiltration did not reach the cricotracheal lumen and was adapted for superficial invasion of the cricoid and trachea. Window resection was defined as resection of the cartilage, including the penetrated area of the cricotracheal lumen. Normal tissue of the cricoid and trachea was retained to the greatest extent possible to allow reconstruction of the cricotracheal defect. Circumferential sleeve resection was adapted for massive cricotracheal infiltration. Curative resection was defined as margin-negative tumor resection, confirmed based on the intraoperative pathological diagnosis. Curative resection was performed for all PTC patients with invasive extrathyroidal extension. The aerodigestive function was preserved or reconstructed when possible. Curative resection was aided by the use of an operating microscope when necessary. During surgery, multiple margin samples were collected for frozen section analyses to confirm margin negativity pathologically. In patients with positive margins, additional resection was performed until a negative margin was achieved. Intraoperative cryosection analysis was performed to preserve the greatest possible extent of normal tissue adjacent to the tumor, as well as to improve functional outcomes. Surgical management was adapted for cricotracheal involvement. Postoperative assessments with cross-sectional imaging and endoscopic examination were performed every 6 months to detect recurrence. Functional outcome was evaluated in terms of the stomal closure rate. (Stomal closure reflects the absence of airway stenosis and aspiration.) Cricotracheal defects are the result of cricotracheal stomata that do not close immediately. Our surgical management of cricotracheal defects consisted of staged operations for stomal closure or reconstruction. Small cricotracheal stomata were closed using a local cutaneous
Management of Cricotracheal Invasion by PTC TABLE 1 Baseline patient characteristics Characteristic
Initial treatment (n = 81)
Treatment for recurrence (n = 29)
Age (years), mean (SD)
61 (15)
64 (10)
Male
21 (26 %)
7 (24 %)
Female
60 (74 %)
22 (76 %)
Sex
Presentation Good
75 (93 %)
25 (86 %)
Poor
6 (7 %)
4 (14 %)
Superficial invasion
51 (63 %)
6 (21 %)
Intraluminal invasion
30 (27 %)
23 (79 %)
Prior distant metastasis, cricotracheal invasion
9 (11 %)
7 (24 %)
Cricotracheal invasiona
a
The presence of intraluminal cricotracheal invasion differed significantly between the initial treatment group and the recurrence treatment group (v2 test, p = 0.0001)
TABLE 2 Locoregional and distant recurrences in patients with cricotracheal PTC invasion Operation
No.
Locoregional recurrence
Aerodigestive recurrence
Distant recurrence
Shave excision
57
6 (11 %)
3 (5 %)
5 (9 %)
Window resection
53
8 (15 %)
3 (6 %)
14 (26 %)
TABLE 3 Stoma status in patients with cricotracheal PTC invasion Operation
No.
No stoma or a temporary stoma
Permanent stoma
Shave excision
57
57 (100 %)
0
Window resection
53
22 (42 %)
31 (58 %)
flap. The original deltopectoral (D-P) flap was used to repair large cricotracheal defects that could not be closed with a local flap but in which the remaining hard structure could still provide internal support. Large cricotracheal defects without this internal support were closed using the D-P flap combined with nasal septal cartilage for hard structure reconstruction. Finally, cricotracheoplasty was performed using the D-P flap to improve phonetic function in patients with a large cricotracheal defect that could not be closed. The Mann–Whitney test was used to compare variables. The 10-year DSS rates were estimated using the Kaplan– Meier method and compared using the log-rank test. Results were considered significant for values of p \ 0.05. Commercially available software (Ekuseru-Toukei 2012; SSRI, Tokyo, Japan) was used for the statistical analyses. RESULTS During the study period, 110 of the 746 PTC patients had cricotracheal invasion. Among the 110 patients enrolled, 61 had tracheal invasion, 44 had cricotracheal
invasion, and 5 had cricoid invasion. The study cohort included 27 men (24.5 %) and 83 women (75.5 %). In all, 81 patients were found to have cricotracheal invasion by PTC at the time of the initial diagnosis, whereas 29 patients were diagnosed with cricotracheal invasion by PTC at cancer relapse. Of the 110 patients, 89 (80.9 %) had been referred from other institutions for surgery to treat cricotracheal invasion by PTC. The mean age of the patients at the time of surgery for laryngeal invasion was 62 years (range 27–92 years). The duration of follow-up after surgery was 7.4 ± 6.3 years (mean ± standard deviation) for patients who survived the procedure. Baseline characteristics did not differ significantly between patients who received initial treatment and those who were treated for recurrence, with the exception of the degree of cricotracheal invasion (Table 1). Altogether, 57 patients with superficial invasion underwent shave excision, and 53 patients with intraluminal invasion underwent window resection. Of the latter 53 patients, only 2 underwent circumferential sleeve resection. In all, 14 and 19 patients had locoregional disease and distal recurrence, respectively. The lesion was located on
S. Moritani
1.0
DSS ratio
0.8 0.6 0.4 0.2 0.0 0
1000
2000
3000
4000
Days after surgery
FIG. 1 Comparison of disease-specific survival (DSS) rates for patients who received initial surgery with superficial and intraluminal invasion of the cricoid-trachea
the upper aerodigestive tract in 6 of the 14 patients with locoregional recurrence. Among these six patients, two had a lesion on the laryngoesophagus, two had a lesion on the cricoid cartilage, one had a lesion on the cricotracheal area, and one had a lesion on the trachea (5.5 %) (Table 2). They were managed with total laryngectomy and an additional window resection as salvage surgery. As a result, only one patient (0.9 %) underwent total laryngectomy. Among the 81 patients who underwent initial surgery, those who had intraluminal cricotracheal invasion had a significantly lower 10-year DSS rate than those who underwent surgery for superficial cricotracheal invasion (44.4 vs. 90.8 %, respectively) (Fig. 1). Functional outcomes were examined in terms of the stomal closure rates. Permanent stomata were present in 31 patients (28 %) with intraluminal invasion (Table 3). The permanent stomata were caused by cricotracheal invasionassociated large cricotracheal defects in 9 patients, bilateral RLN invasion in 11 patients, continuous aspiration without pulmonary complications in 7 patients (window resection and esophageal reconstruction for cricotracheal-esophageal invasion in 4, age-associated depressed swallowing function in 2, depressed swallowing function caused by brain
metastasis in 1), and postoperative early death of 4 patients (acute respiratory distress syndrome caused by respiratory insufficiency from bilateral phrenic nerve invasion in 1, intestinal bleeding in 1, heart failure in 1, and injury to the innominate artery requiring a resected clavicle for mediastinal dissection in 1). Of the 11 patients with bilateral RLN invasion, 5 had had bilateral vocal cord paralysis preoperatively, and 6 had had ipsilateral vocal cord paralysis at a prior surgery and contralateral RLN invasion found at the surgery performed for cricotracheal invasion. Among the 110 patients (71 %) with cricotracheal invasion, 78 also had PTC invasion into other aerodigestive tract structures, including the esophagus (n = 46) and the RLN (n = 71). Among these 78 patients, 39 had invasion of both the esophagus and the RLN, and 39 had only one structure invaded (either the esophagus or the RLN). Permanent stomata occurred more frequently in patients with RLN invasion than in those with esophageal invasion (Table 4). DISCUSSION We found that window resection for intraluminal cricotracheal invasion by PTC produced good outcomes, resulting in a low rate of local recurrence and a survival rate that resembled that after other surgical treatments. However, cricotracheal invasion was accompanied by invasion of other aerodigestive structures in many patients. Thus, treatment of multiple organ invasion of the aerodigestive tract was necessary to improve the postoperative functional outcomes in these patients. Although PTC generally has an excellent prognosis, the rare invasions of the upper aerodigestive tract by PTC have negative effects on prognosis and quality of life. Cricotracheal invasion is an independent negative prognostic factor for survival, and patients with intraluminal extension have a worse prognosis than those with superficial tracheal invasion. The surgical management of airway invasion remains controversial. There is no consensus on the surgical management that should be used (shave excision or
TABLE 4 Stoma status according to the presence or absence of invaded aerodigestive tract structures in patients with cricotracheal invasion Esophageal invasion (n = 110)
RLN invasion (n = 71)a
No stoma or a temporary stoma (n = 79)
Permanent stoma (n = 31)
Yes (n = 46)
(?) 39
25
14
(-) 7
4
3
(?) 32 (-) 32
18 32
14 0
No (n = 64)
RLN recurrent laryngeal nerve, (?) yes, (-) no a
Permanent stoma occurred more frequently in patients with RLN invasion than in those with esophageal invasion (v2, p = 0.0004)
Management of Cricotracheal Invasion by PTC
radical tumor resection) for superficial invasion of the aerodigestive tract. Because it has been shown that shave excision and radical tumor resection produce similar survival rates, it has been suggested that shave excision should be adequate for minimal invasion of the aerodigestive tract in cases in which there is no grossly evident residual tumor.7,9–12 However, it has also been shown that radical tumor resection reduces the chance of local recurrence and improves the postoperative prognosis when compared with shave excision, which has led other researchers to suggest that radical tumor resection is appropriate even for minimal invasion of the aerodigestive tract.1,2,13 There is also no consensus regarding the comparative effectiveness of window resection and circumferential resection as surgical treatments for patients with cricotracheal invasion. It has been reported that the latter should be used for patients with invasion of the trachea by thyroid carcinoma because histological examinations of the circumferential spread showed that invasion on the mucosal side exceeded invasion on the adventitial side.14 Also, suture closure of a window defect is rarely possible. Given the safety of circumferential tracheal resection, there is no clinical role for window resection.3 Shave excision and window resection in this study were associated with 10-year DSS rates of 90.8 and 44.4 %, respectively (p \ 0.0001). Intraluminal extension into the airway was associated with worse survival than superficial invasion of the airway, as has also been noted in previous reports.5–7 However, many of the fatal cases were caused by distant metastases. Only one patient died because of locoregional recurrence. The rate of locoregional recurrence in the upper aerodigestive tract was 5.5 %. These results were equal to or better than the results reported in several previous studies.2,12,15 Only one of the six patients with aerodigestive tract recurrence in our study had to be managed with total laryngectomy. The others were treated successfully with an additional shave excision or sleeve window resection. The rate of total laryngectomy for laryngotracheal invasion was lower in this study than in previous reports.16,17 A closed stoma affects functional outcomes, including postoperative breathing, phonetics, and swallowing. Permanent stomata were present in 31 patients with intraluminal invasion. Nine patients (8.2 %) had permanent stomata caused by large cricotracheal defects that were associated with cricotracheal invasion. These patients had defects that exceeded the semicircular area at the cricoidtrachea connection. Explanations for the poor functional outcome included concurrent cricotracheal invasion by PTC and invasion of other aerodigestive structures, such as the RLN and/or esophagus. Permanent stoma occurred more frequently in patients with RLN invasion than in those with esophageal invasion.
Postsurgical external-beam radiation therapy was not indicated for patients with cricotracheal invasion. Unfortunately, distant metastasis occurred frequently, even in patients with good locoregional control, and became a leading cause of death. We attributed the low rate of locoregional recurrence to the surgical approach adopted, wherein pathologically negative margins were confirmed by frozen section analysis to reduce the risk of incomplete resection and to preserve as much adjacent healthy tissue as possible. Therefore, to ensure successful resection, margin negativity should be confirmed intraoperatively using cryosection analysis. CONCLUSIONS Window resection for cricotracheal invasion by PTC produced good outcomes, resulting in a low rate of local recurrence and survival rates that resembled those reported after other surgical treatments. In many patients, however, cricotracheal invasion was accompanied by invasion of other aerodigestive structures. Treatment of multiple organ invasion of the aerodigestive tract was thus necessary to improve postoperative functional outcomes in these patients.
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