Organ Preservation Surgery for Advanced Unilateral Glottic and Subglottic Cancer

Pierre Delaere, MD; Ann Goeleven, SLT; Vincent Vander Poorten, MD; Robert Hermans, MD; Robert Hierner, MD; Jan Vranckx, MD

Objectives: Functional surgery of unilateral T2b to Key Words: Glottic cancer, subglottic cancer, cricoid T3 glottic cancer and cricoid chondrosarcoma is possible chondrosarcoma, tracheal autotransplantation, revascu- using the technique of tracheal autotransplantation. The larization, organ preservation. objective of this paper is to report the functional and Laryngoscope, 117:1764–1769, 2007 oncologic outcome of 24 consecutive patients treated with this technique between 2001 and 2007. Methods: Seventeen patients, of whom nine were INTRODUCTION previously irradiated, had unilateral glottic cancer with Surgical treatment of advanced cricoid chondrosar- impaired mobility of the vocal fold. Clinical staging was comas and of unilateral T2b to T3 (T2b,T2 glottic cancer T2b to 3N0. Seven patients had a chondrosarcoma of the with impaired mobility; T3, glottic cancer with vocal fold cricoid cartilage. In a first operation, an extended hemi- fixation) glottic cancer usually requires a total laryn- laryngectomy was performed, and a radial forearm flap, gectomy because endoscopic laser resection and chemo- comprising a distal fascial and a proximal skin compo- nent, was transferred to the neck. The fascial paddle was radiation will be successful in only a minority of pa- wrapped around the upper 4-cm segment of cervical tra- tients. Radiation and chemotherapy have not proven to chea, and the skin paddle was used for temporary closure be beneficial in cases of cricoid chondrosarcomas, and of the extended hemilaryngectomy defect. The definitive total laryngectomy is usually inevitable when half of the reconstruction was performed after 2 to 3 months and cricoid cartilage needs resection to obtain clear section consisted of removal of the skin paddle from the laryngeal margins. defect and a transplantation of a patch of revascularized A unilateral T2b to T3 glottic cancer can be diag- cervical trachea to reconstruct the laryngeal defect. nosed as a recurrence after previous radiation therapy Results: Swallowing and speech were restored or as a new primary tumor. Although one side of the after the first operation. The glottic and subglottic larynx may be completely healthy, a total laryngectomy airway lumen was restored during the second operation. The tracheostomy could be closed in 20 patients. is usually advocated for advanced, unilateral glottic After a median follow-up period of 33 (range, 1–66) cancer that is diagnosed after previous radiation ther- 1 months or almost 3 years, 23 patients remained free apy. A new primary unilateral T2b to T3 glottic cancer of tumor recurrence. can be treated by organ preservation chemoradiation Conclusions: Tracheal autotransplantation can be protocols with salvage total laryngectomy in cases of

recommended as a functional treatment for selected T2b persistent or recurrent tumor, with a laryngeal preser- to T3 glottic cancers and for unilateral chondrosarcomas vation rate of approximately 50%.2 of the cricoid cartilage. The technique is oncologically We described a laryngeal reconstruction technique robust while resulting in good postoperative function. that allows for a functional surgical treatment of unilateral chondrosarcomas of the cricoid cartilage and of

selected unilateral T2b to T3 glottic cancer both as pri- From the Department of Otorhinolaryngology–Head and Neck Sur- mary treatment and after previous irradiation.3–7 The gery (P.D., A.G., V.V.P.), the Department of Radiology (R.H.), and the Depart- ment of Plastic and Reconstructive Surgery (R.H., J.V.), University Hospital resection of unilateral T2b to T3 glottic cancers and of K.U. Leuven, Leuven, Belgium. cricoid chondrosarcomas necessitates removal of one Editor’s Note: This Manuscript was accepted for publication May complete half of the cricoid cartilage. This extended 21, 2007. hemilaryngeal defect can be reconstructed with a revas- This work was supported by a grant from the Foundation for Scien- cularized segment of the cervical trachea. The segment tific Research Flanders (FWO) (Fundamental Clinical Research Mandate P. Delaere). of cervical trachea that is used for reconstruction is Send correspondence to Dr. Pierre Delaere, Department of Otolaryn- revascularized by wrapping it with a radial forearm gology–Head and Neck Surgery, University Hospitals Leuven, Kapucijnen- fascia flap. A two-stage reconstruction technique is voer 33, B-3000 Leuven, Belgium. E-mail: [email protected] necessary to bring the cervical trachea with intact DOI: 10.1097/MLG.0b013e3181238397 vascularity inside the hemilaryngectomy defect. The

Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1764 reconstruction technique was designed to fulfill two es- vents adhesions between flap and surrounding tissue and facili- sential requirements: reconstruction of the sphincteric tates dissection during the second operation. The radial forearm and respiratory function of the larynx without compro- vessels were sutured to the neck vessels (radial artery end-to-end mising the oncologic results. the superior thyroid artery; radial vein end-to-side to internal jugular vein). A tracheostomy was placed above the revascularized trachea (Fig. 1B). MATERIALS AND METHODS Definitive reconstruction of the laryngeal defect was per- In a 6 year period (2001–2007), 24 patients were treated. formed during a second operation after 2 to 3 months. The skin Seventeen patients were treated for a squamous cell carci- paddle of the radial forearm flap was removed from the laryngeal noma. These tumors were classified as T (3 patients) and T 2b 3 defect, and the section margins were reevaluated to exclude tu- (14 patients). Nine (2 T ,7T) patients were treated after 2b 3 mor recurrence (Fig. 1C). The fascial-enwrapped segment of re- recurrence of a T glottic tumor treated with radiation therapy. 1 vascularized trachea was isolated, moved upward, and sutured The neck was staged as N in all patients of the series. Seven 0 into the laryngeal defect. The mediastinal tracheal stump was patients were treated for a chondrosarcoma of the cricoid mobilized and sutured to the reconstructed larynx (Fig. 1D). In cartilage. this operation, the vascular pedicle of the radial forearm flap During a first operation, the tumor was resected, the laryn- remained untouched. A tracheostomy was maintained in the su- geal defect was repaired temporarily using the skin paddle of the ture line between the reconstructed larynx and the mediastinal radial forearm flap, and the cervical trachea underwent revascu- trachea. larization. On the tumor side, only the epiglottis, the aryepiglottic The tracheostomy was closed after restoration of all laryn- fold, and the corniculate and cuneiform cartilages were preserved geal functions, usually 1 to 2 months after the second operation. (Figs. 1A, 2A, and 3A). The ipsilateral thyroid lobe and tracheo- The tracheostomy was closed by inverting the skin around the esophageal lymph nodes were removed as well as the lymph tracheostomy, a small procedure performed under local anesthe- nodes at levels II, III, and IV. A radial forearm free flap with a sia. A coronal reformatted computed tomography (CT) scan was fascial paddle and a skin paddle was dissected. The skin paddle taken after the first and second operation. was sutured into the laryngeal defect, and the fascial paddle was wrapped around the cervical trachea for revascularization. An expanded polytetrafluoroethylene (ePTFE) membrane (Preclude RESULTS Pericardial Membrane, 0.1 mm, W.L. Gore and Associates, Inc. The CT scan taken after the first operation showed Flagstaff, AZ) was applied over the fascia flap. The ePTFE pre- a full restoration of the sphincter function at the glottic

Fig. 1. Organ preservation surgery: over- view of longitudinally incised model. (A) Outline of tumor. Tumor (1 ϭ T3 glottic cancer with subglottic extension; 2 ϭ cricoid chondrosarcoma) is resected with inclusion of cricoid cartilage and with preservation of the aryepiglottic fold (asterisk). Anterior commissure is resected if the tumor (1) reaches the anterior border of the vocal fold. (B) First operation. Radial forearm fascia (1) is wrapped (arrow) around the cervical trachea (cartilaginous part) for revascularization. Radial forearm skin flap (2) is sutured into the laryngeal defect for temporary closure. Radial blood vessels (3) are sutured to neck vessels (radial artery end-to-end to superior thyroid artery; radial vein end-to-side to internal jugular vein). Tracheostomy allows (asterisk) respiration. (C) Second operation. Skin paddle (2) is removed from the defect and de-epithelialized (shaded area). Revascularized trachea is isolated (black lines) and transplanted to the laryngeal defect (arrows). The vascular pedicle remains untouched. The tracheal stump will be moved upward and sutured to the reconstructed larynx (dotted arrows). (D) The tracheal patch is sutured into the laryngeal defect. Part of the membranous trachea (asterisk) is resected to allow for anastomosis of the tracheal stump to the reconstructed larynx (arrows).

Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1765 Fig. 2. Organ preservation surgery: over- view of telescopic view of the larynx. (A) Right T3 glottic cancer with delineation of amount of resection. Tumor is resected with inclusion of the anterior commissure and with inclusion of one half of the cricoid cartilage. Only tumors without extension to the supraglottic area are included. (B) Resulting glottic- subglottic defect. At the subglottic level (1), the luminal concavity between the posterior and anterior section line should be restored. At the glottic level, reconstructive tissue should follow the midline posteriorly (2) while a luminal concavity should be provided anteriorly. (3) This configuration will lead to optimal sphincter and respiratory function. Two sutures (white points) are placed at the lateral site of the defect between epiglottis and aryepiglottic fold. These sutures will bring the aryepiglottic fold in a midline position posteriorly. The line indicated by number 2 will be reconstructed by the aryepiglottic fold; lines indicated by numbers 1 and 3 will be reconstructed by the tracheal transplant. (C) The aryepiglottic fold has a midline position posteriorly. (D) Situation after tracheal autotransplantation and after closure of the tracheostomy (arrow in- dicates inverted skin flaps).

level and an incomplete restoration of the subglottic diation pharyngeal hypocontractility. After the second airway lumen (Fig. 3B). Swallowing of solids and liquids operation, the patients could speak after finger occlu- was possible 1 week after the first operation. After the sion of the tracheostomy. Hands-free speaking was pos- first operation, speaking was possible during finger oc- sible after tracheostomy closure. Because of a restricted clusion of the tracheostomy. The voice quality can be airway at the level of the anastomosis between the evaluated on the videos (available online only). Patho- reconstructed larynx and the trachea, the tracheostomy logic examination of the resection specimen revealed all was reopened in two patients. In the first patient section margins to be tumor free. Thyroid cartilage in- (patient 6), the tracheostomy was reopened immedi- vasion (pT4) was seen in three patients who were ini- ately, whereas in the second patient (patient 15), it tially staged as T3. A positive lymph node with extra- was reopened after 4 months. These two patients are capsular spread (patient 18) was found in only one of now speaking with a corked tracheostomy tube. Laryn- the lymph node dissections. geal endoscopy and voice quality after tracheal auto- All 24 patients were tumor free on reevaluation transplantation can be evaluated on the videos (avail- during the second operation (Table I). The respiratory able online only). function was restored by the tracheal patch both at the After a median follow-up period of 33 (range, 1–66) glottic and at the subglottic level (Fig. 2B and C). The months, 22 patients remained free of tumor. One pa- CT scan taken after the second operation showed a full tient (patient 12) died 32 months after reconstruction restoration of the sphincter function at the level of the because of a gastric tumor without evidence of locore- remaining arytenoid while the airway lumen was re- gional tumor recurrence. In one patient (patient 18), a stored both in the anterior glottic and subglottic area local recurrence was detected 2 years after partial lar- (Fig. 3C and D). Some aspiration of saliva was seen yngectomy. A laryngeal preservation rate of 95% was during the first days after operation, and most patients obtained, and 22 patients are alive without evidence of resumed oral feeding after 1 week. One patient (patient locoregional disease. 9) did not succeed in swallowing without aspiration, and a completing total laryngectomy was performed 4 DISCUSSION months after tracheal autotransplantation. Tracheo- Tracheal autotransplantation allows for a func- stomy closure was delayed in another patient (patient tional treatment of T2b to T3 glottic cancer and cricoid 21) because of swallowing problems caused by postirra- chondrosarcomas. A unilateral glottic cancer with impaired

Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1766 Fig. 3. Computed tomography images: coronal reformation. (A) T3 glottic cancer. Tumor (asterisk) is visible on right vocal fold with subglottic extension. Ex- tent of resection is indicated. (B) Situa- tion after first operation. The cervical trachea (between arrowheads) is surrounded by the radial forearm fascia. Expanded polytetrafluoroethylene membrane (aster- isks). Skin flap restores the right side of the larynx. There is good closure between the remaining vocal fold and the skin flap (arrow). Narrow subglottic airway lumen is not sufficient for respiration. (C) Situation after second operation: level of arytenoid. The aryepiglottic fold (asterisk) restores the bulk posteriorly. There is good closure between the remaining arytenoid and the preserved aryepiglottic fold. The subglottic airway lumen is fully restored. Narrow- ing of airway lumen at suture line between trachea and reconstructed larynx (arrow) may be seen in some patients. (D) Situa- tion after second operation: level of membranous vocal fold. The small gap between vocal fold and tracheal patch will restore the airway lumen at the glottic level. The subglottic airway lumen is fully restored. In last patients of this series, silicone stent (arrows) was placed at the time of tracheal autotransplantation to avoid narrowing of the anastomosis between trachea and reconstructed larynx. (Inset) Dumon silicone stent9 (Byron Corp. Woberg, MA) is used to support the anastomosis. Stent with diameter of 16 or 18 mm and length of 5 cm is used. Fenestra (asterisk) with the same dimensions as the opening of the tracheostomy is excised at the anterior wall of the stent. The stent is removed at the time of closure of the tracheostomy. mobility of the vocal fold may occur before or after reconstruction. Extreme care is necessary in previously irradiation. Such a tumor cannot be removed using la- irradiated patients, especially when the pathology re- ser, vertical hemilaryngectomy, or supracricoid laryn- port shows a positive neck node with extracapsular gectomy because a safe caudal tumor margin necessi- spread. tates resection of the cricoid cartilage. Treatment of A revascularized patch of trachea and the pre- previously untreated T3 glottic cancer by primary irra- served aryepiglottic fold are the cornerstones for obtain- diation has yielded local control rates in the 40% to 50% ing good functional results. The extended hemilaryngec- range.1 Of the patients in whom radical irradiation tomy defect with inclusion of the cricoid cartilage is a fails, total laryngectomy is reported to salvage approx- difficult defect because the optimal position of the re- imately half of this group, yielding an overall cure rate constructive tissue is different for the subglottic and of 70%, with a laryngeal preservation rate of the origi- glottic area. In the subglottic area, the graft has to nal 50%.2 The same tumor extension in a previously maintain an adequate airway by providing an adequate irradiated larynx can only be treated by total laryngec- concavity between the anterior and the posterior section tomy. Extended hemilaryngectomy with tracheal auto- line. The revascularized tracheal patch graft meets transplantation for suitable T3 glottic cancers is as these subglottic reconstructive requirements. In the radical as the resection obtained during near-total lar- glottic area, the two opposing functions of respiration yngectomy,8 yielding good laryngeal preservation and and sphincter function need to be addressed. For opti- excellent local tumor control rates. The two-stage ap- mal reconstruction at the glottic level, a balance has to proach is advantageous for the oncologic safety of the be found between optimal respiratory and sphincter procedure. The tumor and the neck nodes are removed function. Complete posterior closure is important for during the first operation, and the second stage allows obtaining a good voice and swallowing function, and, for a reevaluation of the section margins before the therefore, the reconstruction has to be placed in the definitive reconstruction is performed. In our study, posterior midline. Complete glottic closure is less criti- only one patient showed a local recurrence 2 years after cal anteriorly, and therefore a paramedian position of

Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1767 TABLE I. Patients Treated Between 2001 and 2007.

Date of 1st Status of No. Sex Birth (yr) Tumor Stage Operation (mo/yr) Previous Treatment Diet Tracheostomy Current State 1 Male 1926 Carc. pT3N0 08/01 RT (T1N0) Nl Closed Alive/NED 2 Male 1928 Carc. pT3N0 11/01 No Nl closed Alive/NED

3 Male 1948 Chondrosarcoma 02/02 CO2, laser Nl Closed Alive/NED 4 Male 1935 Carc. pT4N0 04/02 No Nl Closed Alive/NED 5 Male 1935 Carc. pT3N0 08/02 No Nl Closed Alive/NED 6 Male 1950 Carc. pT3N0 01/03 RT (T2N0) Nl Corked tube Alive/NED 7 Male 1938 Chondrosarcoma 02/03 No Nl Closed Alive/NED 8 Male 1926 Chondrosarcoma 03/03 No Nl Closed Alive/NED 9 Male 1926 Carc. pT3N0 03/03 RT (T1N0) Nl Laryngectomy Alive/NED 10 Male 1960 Carc. pT4N0 04/03 No Nl Closed Alive/NED 11 Male 1948 Chondrosarcoma 05/03 No Nl Closed Alive/NED 12 Male 1949 Carc. pT3N0 03/04 RT (T2N0) Nl Closed Died 12/06/NED 13 Female 1941 Carc. pT3N0 07/04 No Nl closed Alive/NED 14 Male 1940 Carc. pT2bN0 09/04 No Nl Closed Alive/NED 15 Male 1946 Carc. pT3N0 10/04 No Nl Corked tube Alive/NED

16 Female 1945 Chondrosarcoma 09/04 CO2, laser Nl Closed Alive/NED 17 Male 1947 Carc. pT3N0 11/04 RT (T2N0) Nl Closed Alive/NED 18 Male 1944 Carc. pT3N1 01/05 RT (T1N0) Nl Closed Alive/Rec 01/07 19 Male 1941 Chondrosarcoma 01/05 No Nl Closed Alive/NED

20 Female 1943 Chondrosarcoma 07/05 CO2, laser Nl Closed Alive/NED 21 Male 1934 Carc. pT4N0 08/05 RT (T2N0) Nl Waiting for closure Alive/NED 22 Male 1940 Carc. pT2N0 10/05 RT (T1N0) Nl Closed Alive/NED 23 Male 1935 Carc. pT3N0 08/06 RT (T1N0) Nl Closed Alive/NED 24 Male 1949 Carc. pT2bN0 01/07 No Nl Closed Alive/NED

Carc. ϭ carcinoma; RT ϭ radiotherapy; Nl ϭ normal; NED ϭ no evidence of disease; Rec ϭ recurrence.

the graft will allow good respiratory function. Recon- paired mobility and for cricoid chondrosarcomas. Higher struction of the anterior glottis is easily achieved using morbidity linked with swallowing difficulties is seen when the tracheal autotransplant. Experience in this patient the reconstruction is performed in irradiated patients. series has shown that the aryepiglottic fold is superior However, for irradiated patients, organ preservation sur- for reconstruction of the posterior glottic and supraglot- gery remains a valuable option in patients with unilateral tic area. It can be placed in the midline without inter- glottic cancer. fering with the mobility of the contralateral arytenoid. Four patients did not recover all laryngeal func- Acknowledgments tions. One patient is waiting for tracheostomy closure The authors thank Rudi Knoops, Audio-visual De- until recovery of swallowing, and another patient un- partment, University Leuven, for the production of the derwent a total laryngectomy because of persistent as- video files. piration. Two patients could not be decannulated because of a restricted airway at the level of the BIBLIOGRAPHY anastomosis between the reconstructed larynx and me- 1. Mendenhall WM, Parsons JT, Stringer SP, et al. Stage T3 diastinal trachea. This anastomosis may show a ten- squamous cell carcinoma of the glottic larynx: a compari- dency toward substenosis. This tendency can be antici- son of laryngectomy and irradiation. Int J Radiat Oncol pated by short-term stenting of the anastomosis. From Biol Phys 1992;23:725–732. the experience obtained in this series, we advise the 2. MacKenzie RG, Franssen E, Balogh JM, Gilbert RW, Birt D, Davidson J. Comparing treatment outcomes of radiother- 9 placement of a silicone stent during tracheal auto- apy and surgery in locally advanced carcinoma of the lar- transplantation, as shown in Figure 3D. ynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 2000;47:65–71. 3. Delaere P, Vander Poorten V, Goeleven A, Feron M, Hermans CONCLUSION R. Tracheal autotransplantation: a reliable reconstructive technique for extended hemilaryngectomy defects. Laryn- From both a functional and oncologic point of view, goscope 1998;108:929–934. tracheal autotransplantation can be recommended as a 4. Delaere P, Vander Poorten V, Guelinckx P, Van den Hof B, functional treatment for unilateral glottic cancer with im- Hermans R. Progress in larynx-sparing surgery for glottic

Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1768 cancer through tracheal transplantation. Plast Reconstr 7. Delaere P, Vander Poorten V, Vranckx J, Hierner R. La- Surg 1999;104:1635–1641. ryngeal repair after resection of advanced cancer; an 5. Delaere P, Vander Poorten V, Vanclooster C, Goeleven A, optimal reconstructive protocol. Eur Arch ORL 2005; Hermans R. Results of larynx preservation surgery for ad- 262:910–916. vanced laryngeal cancer through tracheal autotransplanta- 8. Pearson BW, Keith RL. Near-total laryngectomy. In: Johnson tion. Arch Otolaryngol Head Neck Surg 2000;126:1207–1212. JT, Blitzer A, Ossoff RM, Thomas IR, eds. Instructional 6. Delaere P, Hermans R. Tracheal autotransplantation as a Courses, American Academy of Otology-Head Neck Sur- new and reliable technique for the functional treatment of gery, vol 2. St Louis: Mosby, 1990:309–330. advanced laryngeal cancer. Laryngoscope 2003;113: 9. Dumon JF. A dedicated tracheobronchial stent. Chest 1990; 1244–1251. 97:328–332.

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Laryngoscope 117: October 2007 Delaere et al.: Functional Surgery for Glottic and Subglottic Cancer 1769