Stomal recurrence after total laryngectomy for squamous cell carcinoma of the larynx

Stomal recurrence after total laryngectomy for squamous cell carcinoma of the larynx YUTAKA IMAUCHI, MD, KEN ITO, MD, PHD, ESAO TAKASAGO, MD, KEN-ICHI NIBU, MD, PHD, MASASHI SUGASAWA, MD, PHD, and KEIICHI ICHIMURA, MD, PHD, Tokyo and Jichi, Japan

OBJECTIVE: Stomal recurrence after total laryngectomy is one of the most serious issues in the management of laryngeal carcinoma. The management of stomal recurrence, including chemotherapy, radiotherapy, and surgery, has been reported as unsatisfactory. STUDY DESIGN AND SETTING: From 1985 to 1995, 69 patients underwent total laryngectomy for the treatment of laryngeal cancer at the University of Tokyo Hospital. To identify the risk factors for stomal recurrence, we analyzed these patients according to various clinicopathological factors. RESULTS: Stomal recurrence developed in 6 of 69 patients who underwent total laryngectomy for laryngeal carcinoma. Statistical analysis reveals that primary site, preoperative tracheotomy, and paratracheal lymph node metastasis are significant risk factors for stomal recurrence. CONCLUSION: Intensive follow-up should be performed for patients with glottic carcinoma who had preoperative tracheotomy, paratracheal lymph node metastasis, or both to detect stomal recurrence at an early stage. (Otolaryngol Head Neck Surg 2002;126:63-6.)

S

tomal recurrence after total laryngectomy is one of the most serious issues in the management of laryngeal carcinoma. The overall rate of stomal recurrence after total laryngectomy ranges from 3% to 15% according to previous reports.1-17 Because the management of stomal

From the Department of Otolaryngology–Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, (Drs Imauchi, Ito, Takasago, Nibu, and Sugawawa), and the Department of Otorhinolaryngology, Graduate School of Medicine, Tochigi, Jichi Medical School (Dr Ichimura). Reprint requests: Yutaka Imauchi, MD, Department of Otorhinolaryngology–Head and Neck Surgery, Graduate School of Medicine, University of Tokyo, Hong 7-3-1, Bunkyo-Ku, Tokyo 113-8655, Japan; e-mail, [email protected]. Copyright © 2002 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2002/$35.00 + 0 23/77/121515 doi:10.1067/mhn.2002.121515

recurrence, including chemotherapy, radiotherapy, and surgery, has been reported as unsatisfactory,3,5,17 attention should be focused on prevention and the early detection of stomal recurrence. Preoperative tracheotomy,1,4,6,7,10 subglottic invasion,6,8,10,16 pN, and paratracheal lymph node metastasis14-16 have been suggested as major risk factors for stomal recurrence. However, in most reports, paratracheal lymph node metastasis was not considered as an independent variable but instead was analyzed as “lymph node metastasis,” which includes both jugular chain lymph node metastasis and paratracheal lymph node metastasis.16 To determine the reliable risk factors for stomal recurrence after laryngectomy, we analyzed 69 consecutive patients who underwent total laryngectomy for laryngeal squamous cell carcinoma at the Department of Otolaryngology– Head and Neck Surgery, University of Tokyo Hospital. PATIENTS The study population consisted of 69 consecutive patients (68 men and 1 woman) who underwent total laryngectomy for laryngeal squamous cell carcinoma at the Department of Otolaryngology–Head and Neck Surgery, University of Tokyo Hospital, between 1985 and 1995. Patients who underwent partial laryngectomy before total laryngectomy were not included in this study. The mean age at the time of total laryngectomy was 66.3 years (range, 38 to 86 years). Six of these patients had undergone emergency tracheotomy at least 48 hours before laryngectomy. Thirty-six patients had undergone preoperative radiotherapy and 2 had received chemotherapy before surgery. No patients had received postoperative radiotherapy or chemotherapy after laryngectomy. Tumor was classified as supraglottic type in 23 patients, glottic type in 28 patients, subglottic type in 5 patients, and transglottic type in 13 patients, according to TNM classification. On pathological examination, tumors were classified as pT1 in 4 patients, pT2 in 16, pT3 in 16, and pT4 in 33. Fifty-two tumors were classified as pN0, 6 as pN1, and 11 as pN2. Neck dissection was performed unilaterally in 19 patients and bilaterally in 32 patients. Patients were followed up at least for 36 months or until they died. The mean follow-up period was 47.6 months. 63

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Table 1. Stomal recurrence according to clinicopathological features Feature

Primary site Supraglottis Glottis Subglottis Transglottis Timing of tracheotomy Preoperative Intraoperative pT pT1 pT2 pT3 pT4 PN pN0 pN1 pN2a,b,c pN3 Paratracheal lymph node metastasis No Yes Radiation Preoperative Surgery alone

No. of patients

No. of stomal recurrence (%)

23 28 5 13

0 (0) 5 (18) 1 (20) 0 (0)

6 63

2 (33) 4 (6)

4 16 16 33

0 (0) 3 (19) 1 (6) 2 (6)

52 6 11 0

4 (8) 1 (17) 1 (9) 0 (0)

62 7

4 (6) 2 (29)

36 33

3 (8) 3 (9)

P

<0.04

0.08

NS

NS

0.1

NS

Statistical Analysis We hypothesized that the following parameters were risk factors: primary site, preoperative radiotherapy, preoperative tracheotomy, pN, pT, paratracheal lymph node metastasis, and jugular chain lymph node metastasis. To identify potential risk factors for stomal recurrence, χ2 test or Fisher’s exact test was used. P < 0.05 was judged as significant. RESULTS

Distribution of the study population and the incidence of stomal recurrence according to the primary site, timing of tracheotomy, radiation therapy, pT, pN, and paratracheal lymph node metastases are shown in Table 1. Of 69 patients who underwent laryngectomy for laryngeal squamous cell carcinoma, 6 patients had subsequent stomal recurrence (Table 2). For the treatment of stomal recurrence, patient 1 had received irradiation, palliative surgery, and adjuvant chemotherapy. Patient 6 had undergone pharyngoesophagectomy and received adjuvant chemotherapy. Despite these treatments, both patients died of stomal recurrence at 4 and 11 months after salvage surgery, respectively. Patients 2, 3, and 4 had been alive without disease for 65, 119, and 125 months after salvage surgery for stomal recurrences, respectively. These 3 patients received radical resection of recurrent cancers with appropriate margins and postoperative radiotherapy. Patient 5 had surgical

treatment in another hospital but died of recurrence in a cervical lymph node 3 years after salvage surgery. Statistical analyses showed that primary site is a significant risk factor for stomal recurrence. The incidence of stomal recurrence was significantly higher in the patients with glottic carcinoma than in the patients with other primary sites (18% versus 2%, P < 0.04). Tracheotomy and paratracheal lymph node metastases were also considered as marginal significant risk factors (Table 1). The incidence of stomal recurrence was higher in the patients who had preoperative tracheotomy than in those who had intraoperative tracheotomy (33% versus 6%, P = 0.08). The incidence of stomal recurrence was higher in the patients with than in the patients without paratracheal lymph node metastases (29% versus 6%, P = 0.1). According to the correlation analysis, there was a significant correlation between paratracheal lymph node and preoperative tracheotomy (P < 0.01), as well as between paratracheal lymph node metastasis and jugular chain lymph node metastasis (P < 0.01). DISCUSSION

There have been many reports on the risk factors for stomal recurrence after total laryngectomy.1-16 Proposed risk factors for stomal recurrence in previous studies have been preoperative tracheotomy,1,4,6-8,10,11

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Table 2. Details for 6 patients with stomal recurrence

Patient

Age(y)

1 2 3 4 5 6

58 81 81 66 65 60

Primary site

Preoperative radiation (Gy)

Glottis Glottis Glottis Subglottis Glottis Glottis

None 70 None None 56 60

Preoperative tracheotomy

Yes No Yes No No No

Stage

pT3 pN2c pT2 pN0 pT4 pN1 pT4 pN0 pT2 pN0 pT2 pN0

No. of metastatic paratracheal lymph nodes

2 0 1 0 0 0

DFI (mo)†

5.1 0.5 62.9 2.3 19.9 4.7

DFI, disease-free interval from laryngectomy to stomal recurrence.

subglottic invasion of cancer,6,8,10,13 and cervical lymph node metastasis, especially paratracheal lymph node metastasis.14,16 However, there are only a few reports in which paratracheal lymph node metastasis was analyzed separately from jugular chain lymph node metastases as an independent risk factor.16 Our results show that the extent of the tumor of the primary site was a significant risk factor for stomal recurrence. Although we did not perform quantitative analysis of the subglottic extension of the primary site, more-detailed studies on the subglottic extension reported that patients who have in excess of 1 cm of subglottic disease have a high risk of nodal metastasis.18 In our study, paratracheal lymph node metastasis and preoperative tracheotomy were considered as marginally significant risk factors for stomal recurrence after total laryngectomy. It is understandable that paratracheal lymph node metastasis accounts for stomal recurrence, because incomplete paratracheal dissection during laryngectomy may lead to stomal recurrence. Our present finding of the lower incidence of stomal recurrence in the patients with supraglottic carcinoma supported this mechanism, because paratracheal lymph node metastases is quite rare in patients with supraglottic carcinoma. In fact, in the present study, there were no paratracheal metastases in the patients with supraglottic carcinoma, whereas 7 of 46 patients with other primary sites (0% versus 15%, P < 0.1) had paratracheal lymph node metastases. Preoperative tracheotomy has been reported as the main risk factor for stomal recurrence. The implantation of carcinoma cells in the peristomal tissues had been proposed by many as the mechanism of stomal recurrence.2,3 However, this concept of implantation of carcinoma cells is less likely, because sufficient margins can be obtained in a properly performed wide field total laryngectomy, as performed in most institutions. The most likely explanation may be that patients who require a preoperative tracheotomy have more advanced disease and may have a high rate of occult paratracheal

lymph node metastases, and thus preoperative tracheotomy increases the risk of stomal recurrence. This explanation is supported by our finding of the strong correlation between preoperative tracheotomy and paratracheal lymph node metastasis. Indeed, Weber et al16 reported that one third of patients with stomal recurrence had paratracheal lymph node metastasis. Rockley et al14 postulated that stomal recurrence was predominantly due to paratracheal lymphatic metastasis, because patients treated with preoperative tracheotomy had a higher incidence of recurrence in both stomal site and neck nodes, in comparison with the patients without preoperative tracheotomy. In addition, preoperative tracheotomy makes paratracheal lymph node dissection difficult due to inflammation and fibrosis of the peristomal tissues. This might be another reason that patients who underwent preoperative tracheotomy had a greater chance of stomal recurrence. In regard to the management of stomal recurrence, 4 patients (66%) survived stomal recurrence. Although our study is a small series, the outcome is quite favorable in comparison with previous reports.9,12 A possible reason for the better outcome is that stomal recurrences were detected at a relatively early stage in our patients. Stomal recurrence is indeed one of the most serious problems in the management of laryngeal cancer, mainly because it often involves critical structures in the superior mediastinum, including the brachiocephalic artery and vein, carotid artery, aortic arch, and trachea. Sisson et al19 advocated extensive surgery for advanced stomal recurrence. However, in advanced cases, it is difficult to obtain sufficient surgical margins and serious complications have been reported. On the other hand, the patient can be successfully salvaged as long as the recurrence is detected at an early stage, as we showed. Regarding intensive follow-up for the high-risk group, patients who had paratracheal metastasis and/or preoperative tracheotomy and early detection of stomal recurrence may be most important in the

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management of stomal recurrence, especially in the patients with subglottic carcinoma. The prevention of stomal recurrence is another important issue for the management of stomal recurrence. First, a complete paratracheal lymph node dissection and additional resection of the peristomal tissues should be performed in patients who have undergone preoperative tracheotomy. Postoperative radiotherapy to the peristomal site and upper mediastinum has been reported to be effective in the prevention of stomal recurrence.3,16,18,20 In our series, we did not provide postoperative radiotherapy. However, in consideration of our results, we now routinely provide postoperative radiotherapy to the peristomal site and upper mediastinum for patients who had paratracheal lymph node metastases or underwent preoperative tracheotomy, or both. In the present study, we did not provide repeat irradiation therapy for patients who had undergone preoperative full-dose radiation therapy and had paratracheal lymph node metastasis for fear of late side effects of irradiation. Further studies with a larger population and longer follow-up periods are necessary to draw conclusions on the risk factors of stomal recurrence after total laryngectomy, especially with paratracheal lymphatic metastasis and preoperative tracheotomy. REFERENCES 1. Keim WF, Shapiro MJ, Rosin HD. Study of postlaryngectomy stomal recurrence. Arch Otolaryngol 1965;81:183-6. 2. Bauer WC, Edwards DL, McGavran MH. A critical analysis of laryngectomy in the treatment of epidermoid carcinoma of the larynx. Cancer 1962;15:263-70. 3. Schneider RJ, Linderberg RD, Jesse RH. Prevention of tracheal stomal recurrence after total laryngectomy by postoperative radiation. J Surg Oncol 1975;7:187-90.

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4. Stell PM, Van den Broek P. Stomal recurrence after laryngectomy: aetiology and management. J Laryngol Otol 1971;85: 131-40. 5. Mantravardi R, Katz AM, Skolnik EM, et al. Stomal recurrence: a critical analysis of risk factors. Arch Otolaryngol 1981;107:735-8. 6. Modlin B, Ogura JH. Post-laryngectomy tracheal stomal recurrences. Laryngoscope 1969;79:239-50. 7. Condon HA. Postlaryngectomy stomal recurrence: the influence of endotracheal anesthesia. Br J Anaesth 1969;41:531-3. 8. Weisman RA, Colman M, Ward PH. Stomal recurrence following laryngectomy: a critical evaluation. Ann Otol Rhinol Laryngol 1979;88:855-60. 9. Myers EM, Ogura JH. Stomal recurrences: a clinicopathological analysis and protocol for future management. Laryngoscope 1979;89:1121-8. 10. Bonneau RA, Lehman RH. Stomal recurrence following laryngectomy. Arch Otolaryngol 1975;101:408-12. 11. Burnam JA, Hudson WR. Stomal recurrence of malignancy: an evaluation and its significance in the postlaryngectomy patient. South Med J 1967;60:823-6. 12. Davis RK, Shapshay SM. Peristomal recurrence: pathophysiology, prevention, treatment. Otolaryngol Clin North Am 1980;13:499-508. 13. Rubin J, Johnson JT, Myers EN. Stomal recurrence after laryngectomy: inter-related risk factors study. Otolaryngol Head Neck Surg 1990;103:805-12. 14. Rockley TJ, Powell J, Robin PE, et al. Post-laryngectomy stomal recurrence: tumour implantation or paratracheal lymphatic metastasis? Clin Otolaryngol 1991;16:43-7. 15. Barr GD, Robertson AG, Liu KC. Stomal recurrence: a separate entity? J Surg Oncol 1990;44:176-9. 16. Weber RS, Marvel J, Smith P, et al. Paratracheal lymph node dissection for carcinoma of the larynx, hypopharynx, and cervical esophagus. Otolaryngol Head Neck Surg 1993;108:11-7. 17. Breneman JC, Bradshaw A, Gluckman J, et al. Prevention of stomal recurrence in patients requiring emergency tracheostomy for advanced laryngeal and pharyngeal tumors. Cancer 1988;62:802-5. 18. Hanna EYN. Subglottic cancer. Am J Otolaryngol 1994;15: 322-8. 19. Sisson GA, Bytell DE, Becker SP. Mediastinal dissection–1976: indications in newer techniques. Laryngoscope 1977;87:751-9. 20. Leon X, Quer M, Burgues J, et al. Prevention of stomal recurrence. Head Neck 1996;18:54-9.