Annals of Surgical Oncology

, Volume 25, Issue 5, pp 1288–1295 | Cite as

Hypothyroidism and Wound Healing After Salvage Laryngectomy

  • Andrew J. Rosko
  • Andrew C. Birkeland
  • Emily Bellile
  • Kevin J. Kovatch
  • Ashley L. Miller
  • Craig C. Jaffe
  • Andrew G. Shuman
  • Steven B. Chinn
  • Chaz L. Stucken
  • Kelly M. Malloy
  • Jeffrey S. Moyer
  • Keith A. Casper
  • Mark E. P. Prince
  • Carol R. Bradford
  • Gregory T. Wolf
  • Douglas B. Chepeha
  • Matthew E. Spector
Head and Neck Oncology

Abstract

Background

Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established.

Methods

A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n = 182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5 mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed.

Results

The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8–7.1; p = 0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6–49.9; p = 0.001). The risk for fistula (p = 0.003) and reoperation (p = 0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH.

Conclusion

Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med. 1991;324:1685–90.Google Scholar
  3. 3.
    Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Urba S, Wolf G, Eisbruch A, et al. Single-cycle induction chemotherapy selects patients with advanced laryngeal cancer for combined chemoradiation: a new treatment paradigm. J Clin Oncol. 2006;24:593–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Clark JR, de Almeida J, Gilbert R, et al. Primary and salvage (hypo)pharyngectomy: analysis and outcome. Head Neck. 2006;28:671–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Paydarfar JA, Birkmeyer NJ. Complications in head and neck surgery: a meta-analysis of postlaryngectomy pharyngocutaneous fistula. Arch Otolaryngol Head Neck Surg. 2006;132:67–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Li M, Lorenz RR, Khan MJ, et al. Salvage laryngectomy in patients with recurrent laryngeal cancer in the setting of nonoperative treatment failure. Otolaryngol Head Neck Surg. 2013;149:245–51.CrossRefPubMedGoogle Scholar
  8. 8.
    Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41:283–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Clark JR, Gilbert R, Irish J, Brown D, Neligan P, Gullane PJ. Morbidity after flap reconstruction of hypopharyngeal defects. Laryngoscope. 2006;116:173–81.CrossRefPubMedGoogle Scholar
  10. 10.
    Yu P, Robb GL. Pharyngoesophageal reconstruction with the anterolateral thigh flap: a clinical and functional outcomes study. Plast Reconstr Surg. 2005;116:1845–55.CrossRefPubMedGoogle Scholar
  11. 11.
    Rutledge JW, Spencer H, Moreno MA. Predictors for perioperative outcomes following total laryngectomy: a University HealthSystem Consortium Discharge Database study. Otolaryngol Head Neck Surg. 2014;151:81–6.CrossRefPubMedGoogle Scholar
  12. 12.
    Hier M, Black MJ, Lafond G. Pharyngo-cutaneous fistulas after total laryngectomy: incidence, etiology, and outcome analysis. J Otolaryngol. 1993;22:164–6.PubMedGoogle Scholar
  13. 13.
    Sassler AM, Esclamado RM, Wolf GT. Surgery after organ preservation therapy: analysis of wound complications. Arch Otolaryngol Head Neck Surg. 1995;121:162–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Weber RS, Berkey BA, Forastiere A, et al. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91–11. Arch Otolaryngol Head Neck Surg. 2003;129:44–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Andrews BT, Smith RB, Hoffman HT, Funk GF. Orocutaneous and pharyngocutaneous fistula closure using a vacuum-assisted closure system. Ann Otol Rhinol Laryngol. 2008;117:298–302.CrossRefPubMedGoogle Scholar
  16. 16.
    Graboyes EM, Yang Z, Kallogjeri D, Diaz JA, Nussenbaum B. Patients undergoing total laryngectomy: an at-risk population for 30-day unplanned readmission. JAMA Otolaryngol Head Neck Surg. 2014;140:1157–65.CrossRefPubMedGoogle Scholar
  17. 17.
    Carlson GW, Thourani VH, Codner MA, Grist WJ. Free gastro-omental flap reconstruction of the complex, irradiated pharyngeal wound. Head Neck. 1997;19:68–71.CrossRefPubMedGoogle Scholar
  18. 18.
    Chahine KA, Chaffanjon P, Bettega G, Lebeau J, Reyt E, Righini CA. Gastro-omental free flap in the reconstruction of the unfavourable hypopharyngeal defects: a functional assessment. J Plast Reconstr Aesthet Surg. 2009;62:1367–73.CrossRefPubMedGoogle Scholar
  19. 19.
    Chepeha DB, Annich G, Pynnonen MA, et al. Pectoralis major myocutaneous flap vs revascularized free tissue transfer: complications, gastrostomy tube dependence, and hospitalization. Arch Otolaryngol Head Neck Surg. 2004;130:181–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Fung K, Teknos TN, Vandenberg CD, et al. Prevention of wound complications following salvage laryngectomy using free vascularized tissue. Head Neck. 2007;29:425–30.CrossRefPubMedGoogle Scholar
  21. 21.
    Genden EM, Rinaldo A, Shaha AR, Bradley PJ, Rhys-Evans PH, Ferlito A. Pharyngocutaneous fistula following laryngectomy. Acta Otolaryngol. 2004;124:117–20.CrossRefPubMedGoogle Scholar
  22. 22.
    Hanasono MM. Use of reconstructive flaps following total laryngectomy. JAMA Otolaryngol Head Neck Surg. 2013;139:1163.CrossRefPubMedGoogle Scholar
  23. 23.
    Hanasono MM, Lin D, Wax MK, Rosenthal EL. Closure of laryngectomy defects in the age of chemoradiation therapy. Head Neck. 2012;34:580–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Paleri V, Drinnan M, van den Brekel MW, et al. Vascularized tissue to reduce fistula following salvage total laryngectomy: a systematic review. Laryngoscope. 2014;124:1848–53.CrossRefPubMedGoogle Scholar
  25. 25.
    Patel RS, Makitie AA, Goldstein DP, et al. Morbidity and functional outcomes following gastro-omental free flap reconstruction of circumferential pharyngeal defects. Head Neck. 2009;31:655–63.CrossRefPubMedGoogle Scholar
  26. 26.
    Patel UA, Moore BA, Wax M, et al. Impact of pharyngeal closure technique on fistula after salvage laryngectomy. JAMA Otolaryngol Head Neck Surg. 2013;139:1156–62.CrossRefPubMedGoogle Scholar
  27. 27.
    Punthakee X, Zaghi S, Nabili V, Knott PD, Blackwell KE. Effects of salivary bypass tubes on fistula and stricture formation. JAMA Facial Plast Surg. 2013;15:219–25.CrossRefPubMedGoogle Scholar
  28. 28.
    Selber JC, Xue A, Liu J, et al. Pharyngoesophageal reconstruction outcomes following 349 cases. J Reconstr Microsurg. 2014;30:641–54.CrossRefPubMedGoogle Scholar
  29. 29.
    Teknos TN, Myers LL, Bradford CR, Chepeha DB. Free tissue reconstruction of the hypopharynx after organ preservation therapy: analysis of wound complications. Laryngoscope. 2001;111:1192–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Wadsworth JT, Futran N, Eubanks TR. Laparoscopic harvest of the jejunal free flap for reconstruction of hypopharyngeal and cervical esophageal defects. Arch Otolaryngol Head Neck Surg. 2002;128:1384–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Withrow KP, Rosenthal EL, Gourin CG, et al. Free tissue transfer to manage salvage laryngectomy defects after organ preservation failure. Laryngoscope. 2007;117:781–4.CrossRefPubMedGoogle Scholar
  32. 32.
    Miller MC, Agrawal A. Hypothyroidism in postradiation head and neck cancer patients: incidence, complications, and management. Curr Opin Otolaryngol Head Neck Surg. 2009;17:111–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Bhandare N, Kennedy L, Malyapa RS, Morris CG, Mendenhall WM. Primary and central hypothyroidism after radiotherapy for head-and-neck tumors. Int J Radiat Oncol Biol Phys. 2007;68:1131–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Turner SL, Tiver KW, Boyages SC. Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 1995;31:279–83.CrossRefPubMedGoogle Scholar
  35. 35.
    Tell R, Sjodin H, Lundell G, Lewin F, Lewensohn R. Hypothyroidism after external radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phy. 1997;39:303–8.CrossRefGoogle Scholar
  36. 36.
    Tucker HM. Total laryngectomy: technique. Oper Tech Otolaryngol Head Neck Surg. 1990;1:42–4.CrossRefGoogle Scholar
  37. 37.
    Gal RL, Gal TJ, Klotch DW, Cantor AB. Risk factors associated with hypothyroidism after laryngectomy. Otolaryngol Head Neck Surg. 2000;123:211–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Alexander MV, Zajtchuk JT, Henderson RL. Hypothyroidism and wound healing: occurrence after head and neck radiation and surgery. Arch Otolaryngol. 1982;108:289–91.CrossRefPubMedGoogle Scholar
  39. 39.
    Talmi YP, Finkelstein Y, Zohar Y. Pharyngeal fistulas in postoperative hypothyroid patients. Ann Otol Rhinol Laryngol. 1989;98(4 Pt 1):267–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Bohannon IA, Carroll WR, Magnuson JS, Rosenthal EL. Closure of post-laryngectomy pharyngocutaneous fistulae. Head Neck Oncol. 2011;3:29.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Lavelle RJ. Thyroid function after radiotherapy and total larynbecomy in the treatment of carcinoma of the larynx. Ann Otol Rhinol Laryngol. 1971;80:593–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Kojima R, Tsukahara K, Motohashi R, et al. Extent of thyroid resection and thyroid function after postoperative radiotherapy following total laryngectomy or total pharyngo-laryngo-esophagectomy. Int J Clin Oncol. 2017;22(3):438–41.CrossRefPubMedGoogle Scholar
  43. 43.
    Negm H, Mosleh M, Fathy H, Awad A. Thyroid and parathyroid dysfunction after total laryngectomy in patients with laryngeal carcinoma. Eur Arch Otorhinolaryngol. 2016;273:3237–41.CrossRefPubMedGoogle Scholar
  44. 44.
    Hasan Z, Dwivedi RC, Gunaratne DA, Virk SA, Palme CE, Riffat F. Systematic review and meta-analysis of the complications of salvage total laryngectomy. Eur J Surg Oncol. 2017;43:42–51.CrossRefPubMedGoogle Scholar
  45. 45.
    Dedivitis RA, Aires FT, Cernea CR, Brandao LG. Pharyngocutaneous fistula after total laryngectomy: systematic review of risk factors. Head Neck. 2015;37:1691–7.CrossRefPubMedGoogle Scholar
  46. 46.
    Ladenson PW, Singer PA, Ain KB, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160:1573–5.CrossRefPubMedGoogle Scholar
  47. 47.
    Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A. Thyroid function during critical illness. Hormones Athens. 2011;10:117–24.CrossRefPubMedGoogle Scholar
  48. 48.
    Stockigt JR. Guidelines for diagnosis and monitoring of thyroid disease: nonthyroidal illness. Clin Chem. 1996;42:188–92.PubMedGoogle Scholar
  49. 49.
    Righini C, Lequeux T, Cuisnier O, Morel N, Reyt E. The pectoralis myofascial flap in pharyngolaryngeal surgery after radiotherapy. Eur Arch Otorhinolaryngol. 2005;262:357–61.CrossRefPubMedGoogle Scholar
  50. 50.
    Sayles M, Grant DG. Preventing pharyngo-cutaneous fistula in total laryngectomy: a systematic review and meta-analysis. Laryngoscope. 2014;124:1150–63.CrossRefPubMedGoogle Scholar
  51. 51.
    Smith TJ, Burrage KJ, Ganguly P, Kirby S, Drover C. Prevention of postlaryngectomy pharyngocutaneous fistula: the Memorial University experience. J Otolaryngol. 2003;32:222–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Hanasono MM, Barnea Y, Skoracki RJ. Microvascular surgery in the previously operated and irradiated neck. Microsurgery. 2009;29:1–7.CrossRefPubMedGoogle Scholar
  53. 53.
    Rosko AJ, Ryan JT, Wizauer EJ, et al. Dorsal scapular artery as a recipient vessel in the vessel-depleted neck during free tissue transfer in head and neck reconstruction. Head Neck. 2017;39:E72–6.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Andrew J. Rosko
    • 1
  • Andrew C. Birkeland
    • 1
  • Emily Bellile
    • 2
  • Kevin J. Kovatch
    • 1
  • Ashley L. Miller
    • 3
  • Craig C. Jaffe
    • 4
  • Andrew G. Shuman
    • 1
  • Steven B. Chinn
    • 1
  • Chaz L. Stucken
    • 1
  • Kelly M. Malloy
    • 1
  • Jeffrey S. Moyer
    • 1
  • Keith A. Casper
    • 1
  • Mark E. P. Prince
    • 1
  • Carol R. Bradford
    • 1
  • Gregory T. Wolf
    • 1
  • Douglas B. Chepeha
    • 5
  • Matthew E. Spector
    • 1
  1. 1.Department of Otolaryngology-Head and Neck SurgeryUniversity of Michigan Health CenterAnn ArborUSA
  2. 2.Department of BiostatisticsUniversity of Michigan Health CenterAnn ArborUSA
  3. 3.Department of Otolaryngology-Head and Neck SurgeryMassachusetts Eye and Ear InfirmaryBostonUSA
  4. 4.Division of Endocrinology and Metabolism, Department of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborUSA
  5. 5.Department of Otolaryngology-Head and Neck SurgeryUniversity of Toronto Health SystemTorontoCanada

Personalised recommendations