Stoma recurrence after laryngectomy: An analysis of risk factors

Stoma recurrence after laryngectomy: An analysis of risk factors PETERZB.&REN,MD, RICHARD GREINER, MD, and MARC KENGELBACHER,MD, Bern, Switzerland

Data from 130 patients who underwent total laryngectomy for squamous cell carcinoma of the larynx were reviewed. Patients were treated either by primary laryngectomy and planned postoperative radiotherapy or by primary radiotherapy and subsequent salvage laryngectomy. Patients with other treatment modalities and patients with positive margins of resection and laryngectomies for hypopharyngeal cancers were excluded from the study. The stomal recurrence rate with reference to several risk factors, such asprimary tumor stage, location of tumor, lymph node metastases, timing of tracheotomy, and presence of a postoperative pharyngoperistomal fistula, was analyzed. The overall incidence of stomal recurrence was 10%. The treatment modality appeared to have an impact on subsequent stomal recurrence: stornal recurrence developed more often after salvage laryngectomy [18.4%) than after primary laryngectomy with planned postoperative radiation [4.8%). Advanced T stage, N stage, subglottic involvement, and preoperative tracheotomy are risk factors for stomal recurrence only in patients with a primary laryngectomy. $tomal recurrence developed in only four patients after primary laryngectomy with planned radiation. All four patients had more than one risk factor: primary tumor stage T4 [four times), subglottic involvement [three times], and preoperative tracheotomy [three times]. The presence of a postoperative pharyngoperistomal fistula likewise may represent a risk factor for the development of a stomal recurrence. [OTOLARYNGOLHEADNECKSURG1996;114:569-75.]

R e c u r r e n t carcinoma at the tracheal stoma is a dreaded complication in the treatment of laryngeal carcinoma. The incidence of stomal recurrence reported in the literature varies from 2.5% to 15% for patients with squamous cell carcinoma of the larynx, with a mean of 5.8%. 11° Stomal recurrence has been defined by Keim et al. as "a diffuse infiltrate of neoplastic tissue at the junction of amputated trachea and skin. ''1 The lesion may involve the stomal epithelium and/or the parastomal soft tissue. Once it has been diagnosed, the outlook for patients with stoma recurrence is extremely poor, a consequence of progressive tracheostomal obstruction or massive haemorrhage caused by erosion of major vessels. The purpose of this article is to evaluate the From the Departments of Oto-Rhino-Laryngology,Head and Neck Surgery~) and Radiooncology2),Inselspital, Bern, Switzerland. Receivedfor publicationFeb. 23, 1995;revisionreceivedAug. 17, 1995; accepted Aug. 16, 1995. Reprint requests: P. Zb/iren, University Clinic of Oto-RhinoLaryngology,Head and Neck Surgery, lnselspital, CH-3000 Bern, Switzerland. Copyright© 1996by the AmericanAcademyof OtolaryngologyHead and Neck SurgeryFoundation, Inc. 0194-5998/96/$5.00 + 0 23/1/68771

incidence of stomal recurrence in 130 patients with total laryngectomy because of laryngeal carcinoma and to analyze the associated risk factors in these patients. PATIENTS AND METHODS

Data from 130 patients who underwent total laryngectomy for endolaryngeal squamous carcinoma of the larynx from 1978 through 1990 were reviewed. All patients were treated either by primary laryngectomy and planned postoperative radiotherapy or by primary radiotherapy and subsequent salvage laryngectomy. Patients with other treatment modalities, such as patients with positive margins of resection and laryngectomies for cancers of the hypopharynx, were excluded from the study. Surgery combined with radiotherapy was the initial treatment in 81 patients (group A). According tO the International Union Against Cancer TNM classification, n 2 tumors were classified as T2, 49 as T3, and 30 as T4. The target volume of the adjuvant radiotherapy was adapted to the oncologic situation; the tracheal stoma was only included in patients with extralaryngeal tumor infiltration, subglottic extension, and extranodal tumor growth. Radiation was applied with a cobalt beam. In patients with negative 569

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lymph nodes, two opposed lateral radiation fields ( +__wedge) were used; for the anterior field covering the tracheal stoma and the paratracheal lymph nodes, cobalt or electron radiation was used, depending on the clinical situation. A single dose of 200 cGy (80% isodose) was given five times weekly up to the total dose of 50 to 56 Gy. Depending on the histopathologic findings, a boost dose of 8 to 12 Gy was given simultaneously or additionally. The doses for the tracheal stoma were between 50 and 56 Gy. In patients with positive lymph nodes the supraclavicular region or regions and the tracheal stoma were encompassed in the target volume and treated with an anterior cobalt field (total dose, 50 to 56 Gy). A boost dose was given when indicated up to a total stoma dose of 60 to 64 Gy. High-dose radiotherapy followed by salvage laryngectomy was performed in 49 patients (group B). Nine tumros were classified as T1, 25 as T2, 11 as T3, and 4 as T4. None presented initially subglottic tumor involvement. Cobalt irradiation was generally used with opposed lateral fields (___wedge). The supraclavicular region or regions were encompassed in the target volume depending on the finding of cervical lymph nodes. The daily single dose of 200 cGy (80% isodose) was applied five times weekly up to a total dose of 66 to 74 Gy. Several patients had treatment interruptions caused by the acute mucositis reactions, mostly during the sixth week of the treatment period. The stomal recurrence rate was analyzed in each group separately with reference to several factors: primary tumor stage, location of tumor, lymph node metastases, timing of the tracheotomy, and presence of a postoperative pharyngoperistomal fistula. Statistical analysis was done by use of Fisher's exact test.

Only 25 of the 130 patients had cervical lymph node metastasis (Table 5). In group A (surgery plus adjunctive radiation) stomal recurrence developed in 2 of 62 NO, 1 of 10 N1, and 1 of 7 N2 patients. In group B (surgical salvage) stomal recurrence developed in 9 of 43 NO patients.

RESULTS

Timing of Tracheotomy

The overall incidence of stomal recurrence of the 130 patients included in this study was 13 (10%) of 130 (Table 1). The stomal recurrences were diagnosed from 4 to 30 months after laryngectomy with a mean onset of 10 months.

In group A (surgery plus adjunctive radiation), 36 of 81 patients had had a tracheotomy at least 24 hours before laryngectomy (Table 6). Three (8.3%) of them had stomal recurrence, but only 1 (2.2%) of 45 patients without previous tracheotomy had stomal recurrence. The difference in recurrence rate is statistically not significant (p = 0.229). In group B (surgery salvage), 23 of 49 patients had had a previous tracheotomy. Stomal recurrence developed in 4 (17.4%) of them. Five (19.2%) of 26 patients without previous tracheotomy had stomal recurrence later. There was no difference in the incidence of stomal recurrence between patients

Treatment Modality

Eighty-one patients underwent laryngeal resection and planned adjunctive radiation (group A); four (4.8%) had recurrent disease at the stoma (Table 2). Of the 49 patients who underwent a salvage laryngectomy (group B), 9 (18.4%) had stomal recurrence. The treatment used has an im-

pact on subsequent stomal recurrence. The observed difference in recurrence rate between group A and B is statistically significant (p = 0.016). T Stage

In group A, with 81 patients, only 4 (13.3%) of 30 with T4 tumors had recurrent disease at the stoma (Table 3). In group B (surgical salvage) stomal recurrence developed in 1 (11.1%) of 9 patients with initially T1 lesions, 4 (16%) of 25 with T2 lesions, and 4 (36.4%) of 11 with T3 lesions. Site of Primary Lesion

In group A (surgery plus adjunctive radiation), 36 of 81 patients had tumor extension into the subglottis (Table 4). Three (8.3%) of them had stomal recurrence later. Stomal recurrence developed in only 1 (2.2%) of the 45 patients without subglottic tumor involvement. The difference in recurrence rate is statistically not significant (p = 0.269). In group B (surgical salvage), tumor recurrence in 16 of 49 patients presented neoplastic extension into the subglottis. Three (18.7%) of them had stomal recurrence. Stomal recurrence developed in 6 (18.2%) of 33 patients without subglottic tumor involvement. There was no difference in the incidence of stomal recurrence between patients with (6 of 33) or patients without (3 of 16) tumor extension into the subglottis. N Stage

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Table 1. Patients with stomal recurrence after total laryngectomy: Primary iaryngectomy (nos, I through 4 [group A]] and salvage laryngectomy [nos, 5 through 13 [group B]] Patient no.

TNM classification

Tumor extension

Preoperative tracheotomy

Pharyngoperistomal fistula

1 2 3 4 5 6 7 8 9 10 11 12 13

T4N0 T4N 1 T4N0 T4N2 T3N0 T3N0 T2N0 T1 NO T3N0 T3N0 T2N0 T2N0 T2N0

Transglottic Glotto-subglottic Subglottic Supraglottic Glotto-supraglottic Glotto-subglottic GIottic Glottic Transglottic GIotto-supraglottic Glottic GIottic Glotto-subglottic

Yes Yes Yes No No No Yes Yes Yes Yes No No No

No No No Yes Yes Yes Yes No No No No No No

Subglottic tumor extension, preoperative tracheotomy, and pharyngoperiostomalfistula represent risk factors.

Table 2. Incidence of stomal recurrence according to treatment

Treatment

No, of No. of recurrences patients [%]

ment modality, initial T stage, subglottic tumor extension, emergency tracheotomy, and extent of lymph node involvement, are controversial on the basis of a literature search. Treatment Modality

Surgery plus adjunctive radiotherapy Radiation followed by surgical salvage

81 49

4 (4.8) 9 (18.4)

with (4 of 23) or patients without (5 of 26) preoperative tracheotomy. Postoperative Pharyngoperistomal Fistula

Six of 81 patients in group A (surgery plus adjunctive radiation) had a postoperative pharyngoperistomal fistula (Table 7). Stomal recurrence developed in 1 (16.6%). Only 3 (4%) of 75 patients without postoperative pharyngoperistomal fistula had stomal recurrence. The difference in recurrence rate is statistically not significant (p = 0.269). Ten of 49 patients in group B (salvage surgery) had a postoperative pharyngoperistomal fistula. Three (30%) of them had stomal recurrence. Six (15.4%) of 39 patients without a fistula had stomal recurrence. DISCUSSION

Recurrence at the tracheostomy site usually occurs within the first year after laryngectomy, as in 11 of our 13 cases.l° The precise pathogenesis of stomal recurrence is unknown. Submucosal extension of the neoplasm and local tumor cell implantation have been suggested as possible sourcesJ 2 Other factors associated with stomal recurrence, such as treat-

Most studies do not differentiate between "primary laryngectomy" and "salvage laryngectomy." Several authors could not demonstrate an influence of treatment methods on the occurrence of stomal recurrence. 7'1° However, Montravadi et al. 7 noted that of seven glottic tumors treated with irradiation and surgical salvage, four developed stomal recurrences. With radiation failures, there may be greater invasion of cartilage and extension into subglottic areas. 13 Our analysis of 130 patients by treatment methods disclosed the incidence of stomal recurrence to be 4.8% (4 of 81) in group A (laryngectomy with planned adjunctive radiotherapy) and 18.4% (9 of 49) in group B (salvage laryngectomy). The observed difference is statistically significant. Furthermore, possible risk factors such as subglottic extension of the tumor and preoperative tracheostomy are valid only for group A (primary laryngectomy with planned adjunctive radiotherapy). In group B (salvage surgery), these risk factors do not influence the rate of stomal recurrence. T Stage

A controversy has focused on the importance of preoperative tumor extent and the development of stomal recurrence. Several authors observed a cor-. relation 4'7'14 as demonstrated also in our study. In

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Table 3. Incidence of stomal recurrence according to stage of primary lesion Surgery plus adjunctive radiation [n = 81]

Radiation followed by surgical salvage [n = 49]

Stage

No. of patients

No. of SR [%]

No. of patients

No. of SR (%1

T1 T2 T3 T4

0 2 49 30

0 0 0 4 (13.3)

9 25 11 4

1 (11.1) 4 (16) 4 (36.4) 0

SR, Stomal recurrences.

Table 4. Incidence of stomal recurrene according to subglottis involvement Surgery plus adjunctive radiation [n = 81] Subglottis involvement

Radiation followed by surgical salvage (n - 49]

No. of patients

No. of SR [%]

No. of patients

No. of SR (%]

36 45

3 (8.3) 1 (2.2)

16 33

3 (18.7) 6 (18.7)

Involved Not involved SR, Stomal recurrences.

Table 5. Incidence of stomal recurrence according to initial stage of lymph node Surgery plus adjunctive radiation [n

=

81]

Radiation followed by surgical salvage [n - 49]

Stage

No, of patients

No. of SR [%]

No. of patients

No. of SR [%]

NO N1 N2 N3

62 10 7 2

2 (3.2) 1 (10) 1 (14) 0

43 4 1 1

9 (21) 0 0 0

SR, Sternal recurrences.

Table 6. Timing of tracheotomy and stomal recurrence Surgery plus adjunctive radiation [n = 81)

Radiation followed by surgical salvage In = 49]

Timing

No. of patients

No. of SR [%]

No. of patients

No. of SR [%]

Preoperative tracheotomy No previous tracheotomy

36 45

3 (8.3) 1 (2.2)

23 26

4 (17.4) 5 (19.2)

SR, Stomal recurrences.

contrast, other authors believed the occurrence of stomal recurrence to be independent of the initial primary tumor stage. 1'2'u Extent of Lymph Node Involvement

The initial presence of lymph node metastases seems to contribute to the development of stomal recurrence. In several studies, the incidence of stomal recurrence is higher in patients with advanced neck disease6,1547; in other series, a correlation between neck disease and incidence of stomal

recurrence could not be observed. 1'4'5 These different observations are probably the result of the retrospective manner of the studies with different diagnostic concepts. Weber et al. 1~analyzed in a prospective study the paratracheal lymph node tumor involvement of laryngeal, hypopharyngeal, and esophageal carcinomas. In 14 of 62 patients with cervical metastases and in 15 of 79 patients without cervical metastases, he found paratracheal lymph node metastases. Thus 15 (52%) of 29 patients had paratracheal node metastases in absence of cervical

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Table 7. Incidence of stomal recurrence according to postoperative pharyngoperistomal fistula Surgery plus adjunctive radiation [n = 81]

Pharyngoperistomal fistula No pharyngoperistomal fistula

Radiation followed by surgical salvage In = a9]

No. of patients

No, of SR [%]

No. of patients

No. of SR (%)

6 75

1 (16.6) 3 (4)

10 39

3 (30) 6 (15.4)

SR, Stomal recurrences.

metastases. In our study the number of patients with lymph node metastasis is small. Neck disease may be a risk factor.

Subglottic Extension Because of the proximity of a subglottic tumor to the tracheostoma, it seems logical to consider the presence of a tumor in the subglottis (transglottic or primary subglottic tumors) to be the most important risk factor in stomal recurrence. Subglottic extension of the tumor was observed in about half of the patients with stomal recurrence. 7 Patients with initial subglottic extension of the tumor have a stomal recurrence rate of 14% to 23%. 7'1°In our series 6 of 13 patients with stomal recurrence had subglottic extension. In group A (laryngectomy plus adjunctive radiotherapy), only 3 (8%) of 36 patients with initial subglottic extension of the tumor had stomal recurrence. Several mechanisms have been suggested to explain the high risk of subglottic tumor in the development of stomal recurrence. Subglottic cancers have a tendency toward circumferential growth and cartilage invasion. Spread tends to occur outside the larynx through the cricothyroid membrane to the trachea or hypopharynx.1°'19'2° The lymph drainage from the subglottic region passes to the paratracheal lymph nodes. These lymph nodes are rarely palpable. Furtlhermore, they are not routinely included in neck dissectionY Emergency Tracheotomy "Prior tracheotomy" is the most discussed and controversial factor. Preoperative tracheotomy is defined as a tracheotomy done at least 24 hours before laryngectomy.1 The increased incidence of peristomal :recurrence associated with preoperative tracheotomy was observed by numerous authors. 8,9,17,21 They hypothesized that the increased risk of stomal recurrence after preoperative tracheotomy was a result of dislodged tumor cells having had the opportunity to implant in the fresh granu-

lation tissue of the stoma wound. This hypothesis of tumor cell implantation was also considered responsible for recurrence at the gastrostomy site after open gastrostomy on a patient with stage 4 squamous cell carcinoma of the tongue, 22at the donor site of a pectoralis major myocutaneous flap used to close a defect in the retromolar trigone and for reconstruction after total glossectomyY,24 Recently, recurrent carcinoma was also diagnosed in the abdominal wall after a percutaneous endoscopic gastrostomyY Several authors could not find any association between preoperative tracheotomy and the incidence of stomal recurrence. 7'1°'26,27 In our study we could only observe an increased incidence of stomal recurrence after preoperative tracheotomy in group A (laryngectomy and adjunctive radiotherapy). However, all three patients in this group with stoma recurrence after preoperative tracheotomy had initial advanced cancers (T4) with subglottic tumor extension (Table 1).

Postoperative Pharyngoperistomal Fistula To our knowledge, this is the first study analyzing the correlation between pharyngoperistomal fistula and stomal recurrence. Our study disclosed that the incidence of stomal recurrence is higher in patients with than in patients without a postoperative pharyngoperistomal fistula. This could be the result of viable dislodged tumor cells having had the opportunity to implant in the perifistular tissue near the tracheostoma. Once a stomal recurrence becomes evident, the prognosis is dismal despite aggressive surgical therapy or high-dose irradiationY -3° Only early lesions could be treated successfully with surgery?1 Death in these patients is commonly caused by airway obstruction or hemorrhage. In the series of Rubin et al. 1°with 15 stomal recurrences, 13 patients died of their disease within 1 to 22 months after onset of recurrence, with a mean of 9 months. Two patients, in whom recurrence was limited to the

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superior aspect of the stoma, were cured with extensive surgical resection. Because the treatment of stomal recurrence has been far from satisfactory, efforts at prevention seem to offer the most promising solution. Where there is evidence of subglottic extension of the tumor, extended dissections were suggested29'3°'32: removal of wide tracheal margins, pretracheal fascia, paratracheal lymph nodes, and recurrent lymphatics up to the suprasternal notch. For obstructing laryngeal carcinoma, some authors propose an emergency laryngectomy rather than a tracheotomy followed by elective laryngectomy. 17,33Furthermore, the tracheostomy, paratracheal lymph nodes, and superior mediastinum should b e routinely included in radiotherapy portals for laryngeal cancers with risk factors for stomal r e c u r r e n c e . 14'1s'34 To avoid tumor implantation, irrigation of the wound before closure or excision of an existing tracheotomy are recommended.6,17,3s CONCLUSIONS

The treatment modality has an impact on subsequent stomal recurrence. Patients treated with highdose radiotherapy followed by salvage laryngectomy have stomal recurrence more often than patients treated by primary laryngectomy. The difference is statistically significant. Possible risk factors for an ultimate stomal recurrence such as T stage, N stage, subglottic involvement, and preoperative tracheotomy are valid only in patients treated by primary laryngectomy with planned postoperative radiation. Thus a statistical significance of these risk factors could not b e observed. In group A (surgery plus planned radiation) only patients with tumor stage T4 had stomal recurrence; in group B (surgical salvage) stomal recurrence was observed independently of the initial T stage. In group A (surgery plus planned postoperative radiation), all four patients with stomal recurrence had more than one risk factor: primary tumor stage T4 (four times), subglottic involvement (three times), and preoperative tracheotomy (three times). Therefore the impact of every individual risk factor is difficult to assess. The findings of this study indicate that the presence of a postoperative pharyngoperistomal fistula may represent a risk factor. Nevertheless, the number of patients in our series is too small to demonstrate the correlation by means of statistics.

Special thanks to Daniel Dietrich for the statistical analysis. REFERENCES 1. Keim WF, Shapiro M J, Rosin HD. Study of postlaryngect0mY stomal recurrence. Arch Otolaryngol 1965;81:183-6. 2. Stell PM, Van Den Broek P. Stomal recurrence after laryngectomy: aetiology and management. J Laryngol Otol 1971 ;850:131-40. 3. Kuehn PG, Teunant R. Surgical treatment of stomal recurrences in cancer of the larynx. Am J Surg 1971;122:445-50. 4. Bonneau RA, Lehman RH. Stomal recurrence following laryngectomy. Arch Otolaryngol 1975;101:408-12. 5. Myers EM, Ogura JH. Stomal recurrences: a clinicopathological analysis and protocol for future management. Laryngoscope 1979;89:1121-38. 6. Weisman RA, Colman M, Ward PH. Stomal recurrence following laryngectomy. A critical evaluation. Ann Oto11979; 88:855-60. 7. Mantravadi R, Katz AM, Skolaik EM, Becker S, Freehling D J, Friedman M. Stomal recurrence. A critical analysis of risk factors. Arch Otolaryngol 1981;107:735-8. 8. Biguardi L, Vavioli L, Staffieri A. Tracheostomal recurrences after laryngectomy. Arch Otorhinolaryngol 1983;238:107-13. 9. Barr GD, Robertson AG. Stomal recurrence: a separate entity? J Surg Oncol 1990;44:176-9. 10. Rubin J, Johnson JT, Myers EN. Stomal recurrence after laryngectomy: interrelated risk factor study. OTOta~YNOOL HEAD NECI~SURe 1990;103:805-12. 11. Hermanek P, Scheibe O, Spiessl B, Wagner G. TNM classification of malignant tumors. Fourth, fully revised ed. Berlin: Springer, 1987. 12. Batsalis JG, Hybels R, Rice DH. Laryngeal carcinoma. Stomal recurrences and distant metastases. Can J Otolaryngol 1975;4:906-14. 13. Brandenburg JH, Condon KG, Frank TW. Coronal sections of larynges from radiation-therapy failures. A clinicalpathologic study. OTOLARYNGOLHEAD NECK SURG 1986;95: 213-8. 14. Schneider J J, Lindberg RD, Jesse RH. Prevention of tracheal stomal recurrence after total laryngectomy by postoperative irradiation. J Surg Oncol 1975;7:187-90. 15. Modlin B, Ogurd J. Post-laryngectomy tracheal stomal recurrence. Laryngoscopy 1969;79:239-50. 16. Loewy A, Laker HI. Tracheal stoma problems. Arch Otolaryngol 1968;87:477-83. 17. Rockley T J, Powell J, Robin PE, Reid AP. Post-laryngectomy stomal recurrence: tumor implantation or paratracheal lymphatic metastasis? Clin Otolaryngol 1991;16:43-7. 18. Weber RS, Marvel J, Smith P, Hankins P, Wolf P, Goepfert H. Paratracheal lymph node dissection for carcinoma of the larynx, hypolarynx, and cervical esophagus. OTOLARYNGOL HEAD NECKStJRG 1993;108:11-7. 19. O1ofsson J. Specific features of laryngeal carcinoma involving the anterior commissure and the subglottic region. Can J Otolaryngol 1975;4:618-36. 20. Harrison DFN. The pathology and management of subglottic cancer. Ann Otol Rhinol Laryngol 1972;80:6-12. 21. Burnam JA, Hudson WR. Stomal recurrence of malignancy: an evaluation and its significance in post-laryngectomy patient. South Med J 1967;60:823-6.

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22. Alagaratnam TT, Oug GB. Wound implantation - a surgical hazard. Br J Surg 1977;64:872-5. 23. Robbins KT, Woodson GE. Chest wall metastasis as a complication of myocutaneous flap reconstruction. J Otolaryngol 1984;13:13-4. 24. Cart R J, Gilbert PM. Tumor implantation to a temporalis muscle flap donor site. Br J Oral Maxillofac Surg 1989;24: 295-7. 25. Preyer S, Thai P. Gastric metastasis of squamous cell carcinoma of head and neck after percutaneous endoscopic gastrostomy-report of a case. Endoscopy 1989;21:295-7. 26. Coancon HA. Post-laryngectomy stomal recurrence: the influence of endotracheal anesthesia. Br J Anaesth 1969;41: 531-3. 27. DeJong PC. Intubation and tumor implantation in laryngeal carcinoma. Practica Otorhinolaryngol 1969;31:119-21. 28. Sisson GA, ByteU DE, Becket SP. Mediastinal dissection1976: indications and newer techniques. Laryngoscope 1977; 87:751-9.

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