- Email: [email protected]
Surgical Removal Followed by Radiotherapy for Refractory Vocal Process Granuloma
Surgical Removal Followed by Radiotherapy for Refractory Vocal Process Granuloma *Yongli Song, *Li Shi, *Yu Zhao, *Daqing Zhao, †Mei Shi, and *Zhihong Deng, *yXi’an, China Summary: Objective/Hypothesis. Vocal process granuloma (VPG) is a challenging disease because of its multifactorial etiology, irrespective of treatments. Conservative treatments had shown limited effects, while surgical attempts of removing lesions were only indicated in certain conditions for high recurrent rates. However, a group of patients remained with refractory disease. The objective of this study was to describe the use of surgical removal followed by radiation therapy in the management of patients with refractory VPG. Study Design. Retrospective reviews were conducted in patients with refractory VPG to evaluate the effects of surgical removal followed by radiation therapy and compared with that of surgical removal alone. Methods. Twenty-one patients with refractory disease were enrolled in our study. Fifteen patients accepted surgical removal followed by radiation therapy the day after operation in a total dose of 15 Gy. Six patients who refused radiation therapy accepted surgical removal alone. All patients were followed up for 3–6 years and laryngoscope results were studied in all patients. Results. All of the 15 patients treated with surgical removal followed by radiation therapy in low dose got the disease eliminated completely with mild complications. Recurrences were observed during the 2 weeks to 3 months after operation in five of the six patients who accepted surgical removal alone, whereas no recurrence was observed in the other one in whom the granuloma was believed to be caused by intubation injury. Conclusion. This initial study showed that surgical removal followed by radiation therapy in low dose was a safe and an effective approach to manage VPG with a potential for clinical application, but further studies in a larger cohort for a longer term were needed. Key Words: Vocal process granuloma–Surgical removal–Radiation therapy.
INTRODUCTION Vocal process granuloma (VPG) is an uncommon benign disease that usually develops in the vicinity of the posterior vocal fold, adjacent to the vocal process. It represented a significant treatment challenge because of its tendency to recur irrespective of treatments. The cause of the VPG was not clear yet, although some factors such as hyper functional vocal behaviors, intubation injury, or reflux from the esophagus to the pharynx have been proved to cause or exacerbate the pathology. In recent years, studies had described the benefits of conservative treatments, including voice therapy, antireflux treatments, combined antireflux treatments and voice therapy, or inhaled triamcinolone to certain degree.1,2 More aggressive treatment such as a botulinum toxin injection into vocal process was proved to be a useful adjunctive therapy.3 But all of those therapies would last a relative long period during which patients had to suffer different symptoms and were prone to quit therapy. Surgical excisions were not indicated for the original treatment of VPG for high recurrent rates. It may be indicated to remove obstructive lesions or lesions that cause repetitive throat clearing that perpetuate the disease and to treat the suspected malignancy or refractory diseases ineffective to other therapies.4 But how to
Accepted for publication August 5, 2011. From the *Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China; and the yDepartment of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China. Address correspondence and reprint requests to Zhihong Deng, Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle Western Road, 710032 Xi’an, China. E-mail: [email protected] Journal of Voice, Vol. 26, No. 5, pp. 666.e1-666.e5 0892-1997/$36.00 Ó 2012 The Voice Foundation doi:10.1016/j.jvoice.2011.08.004
reduce the recurrent rate of the postoperative disease remained a tough problem. Radiation therapy was traditionally applied to treat malignant diseases and recently was reported to be effective in treating benign proliferative diseases in low dose.5 Several studies had showed the benefits of radiation treatment in VPG.6,7 Recently, Mitchell described the favorable prognosis of treating one refractory laryngeal granuloma by excision followed with immediate radiotherapy, which provided us anecdotal experience.8 In this retrospective study, we studied cases with refractory VPG, whose pathology had failed to resolve completely with medical, surgical, or combined surgical-medical treatments. Patients were treated by granuloma excision followed with immediate radiotherapy, and all responded well to our treatments. MATERIALS AND METHODS Patients presented to the ENT department of the Xijing Hospital of the Fourth Military Medical University during January 2004–December 2007 with established VPG were studied. The inclusion criteria for our study were (1) patients with VPG who had been treated routinely with antireflux, voice therapy, surgery, or other therapy before and showed no improvement; (2) patients who suffered sustained symptoms such as hoarseness, chronic cough and/or throat clearing, globus sensation, or dyspnea; and (3) patients who refused persistent conservative treatments. There were 21 patients who enrolled in our study including 16 men and five women, with a mean age of 46.3 years in men, and 44.6 years in women. Causes attributed to the granuloma were believed to be voice abuse (five patients), intubation injury (one patient), chronic reflux (six patients), and
Yongli Song, et al
666.e2
Surgical Removal Then Radiotherapy for Refractory VPG
others unknown (nine patients). All patients with reflux were referred to the specialists and were diagnosed as reflux esophagitis by gastroscopy (Table 1). All patients were counseled about the treatment protocol and informed of possible complications. Five patients refused radiation therapy and accepted operation removal alone, while others were treated with granuloma excision and followed immediate radiotherapy. All operations were carried out under general anesthesia. Granulomas were removed using microsuspension laryngoscope and CO2 laser (6 W, depth in 2 mm, inline modal) with the perichondrium tissues on the surface of arytenoids remaining. All patients were treated with antibiotics for 3 days after operation, and were requested voice rest for at least 2 weeks. Patients were assessed clinically at monthly intervals after the operation, and the laryngoscope was taken for each patient. Complete responders were followed every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. The radiation fields of the granuloma were precisely conformed in 3-dimensions the day before the operation. Patients started radiation therapy within the following 24 hours after operation. During the treatment, patients were immobilized with a thermoplastic head, neck, and shoulder mask to ensure precisely matching to the granuloma and the reproducibility of the treatments. Patients underwent treatment planning using the Eclipse/Helios treatment planning system with 6-MV photons. Beams were chosen to ensure that more than 95% of the dose encompassed the target region, 3 Gy per day of radiation
was given on 5 days, reaching a total of 15 Gy in 25 fractions, centered on the larynx demonstrated in Figure 1. RESULTS Six patients who refused radiotherapy accepted surgical removal alone, and in five patients recurrence occurred during 2 weeks to 3 months after operation. In the other one, in whom the granuloma was believed to have been caused by intubation injury, no recurrence was observed. All 15 patients who accepted surgical removal followed with radiation therapy presented improvement of voice and release of symptoms soon after operation. During the follow-up period, lesions were dismissed in patients 1–2 months after treatment, and no recurrence was observed (ranging from 3 to 6 years) (Figure 2). Two cases complained of light sore throat that disappeared 1 month after radiation therapy. No other complication, such as flare of local skin or induced malignancy, was observed. DISCUSSION It is considered that the cause of VPG was not clear in many patients although some factors were identified. Reflux might be a primary cause of ulceration and then granuloma formation in the vocal process. Voice abuse and throat clearing might lead to vocal process friction and then cause or exacerbate the pathology. In our study, the causes of the granuloma were believed to be voice abuse (five patients), intubation injury (one patients), chronic reflux (six patients), and others idiopathic,
TABLE 1. Prior Treatments and Duration Antireflux (Months) Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Surgical Excision (n)
PPI
H2A
Speech Therapy
Other Therapy
Recurrent Times
1 2 2 1 3 2 1 1 2 3 2 1 1 1 1 3 1 1 1 3 1
10 8 12 12 24 24 17 6 14 12 9 3 7 11 19 6 12 9 6 12 None
3 3 3 None None 3 None 3 3 3 None None None 3 3 None 3 None None 3 None
Yes No Yes No No Yes No No Yes Yes No No Yes Yes No Yes No No Yes Yes No
Triamcinolone inhaler Triamcinolone inhaler Ciprofloxacin Ciprofloxacin Triamcinolone inhaler Triamcinolone inhaler Triamcinolone inhaler Ciprofloxacin Botulinum toxin injection Ciprofloxacin Triamcinolone inhale Ciprofloxacin Triamcinolone inhaler Botulinum toxin injection Botulinum toxin injection Triamcinolone inhaler Triamcinolone inhaler Botulinum toxin injection Triamcinolone inhaler Ciprofloxacin Triamcinolone inhaler
2 3 3 2 6 4 2 2 3 4 3 3 2 2 2 4 2 3 2 5 2
Abbreviations: PPI, proton pump inhibitor; H2A, H2 antagonist.
666.e3
Journal of Voice, Vol. 26, No. 5, 2012
FIGURE 1. The target radiation field was precisely located with 3-dimensional conformal radiation system, and the targeting information was got in width, height, and depth before radiation therapy. The field circled by the red line was the target radiation field indicated by white arrow.
which were in accordance with earlier studies.9 In the past decades, treatments addressed to get rid of causes for granuloma, such as antireflux treatments and voice therapy, were proved effective (8/10).10 Recently, a study reported that by long-term observation (from 13 weeks to 70 weeks, mean 30.6 weeks), the VPG can be cured at high remission rates (81%) without implementing specific treatments.11 As a result, there remained some patients with diseases, irrespective of treatments; however, in our study, all patients suffered recurrent lesions that had been treated with therapies such as antireflux treatments, voice therapy, or combined treatments before presenting to our department (range from 6 months to 24 months). It may be because of the idiopathic disease that led to its irrespective of treatments or shorter observation term before the remission of the granuloma. Excision of granuloma was not indicated in the original treatment of VPG for the high recurrence rate. It was reported that the recurrence rate was as high as 90% after excision of the granuloma, in a range from 15 to 51 months.4,12 In our study, all patients had recurrent diseases after operation before referring to ours (range from 1 to 3 times), and there were five patients who recurred in six accepted operations alone in about 2 weeks–3 months. Attempts to reduce recurrence rate after operation had been tried, including the new technology, surgical skills, or adjunct therapy. It has been suggested that the type of surgical excision, laser or ‘‘cold steel,’’ may predispose to recurrence, and laser was favored for its ability of precise excision and hemostasis, although it may have reverse thermal effects on
surrounding tissues. Botulinum toxin can temporarily weaken the muscles into which it is injected. Injecting it into the vocal process may reduce the adduction and contact forces at the pathology site, which may eliminate the granuloma and reduce the recurrence after operation, but the effects were not maintained and patients had to suffer hoarseness secondary to the injections.3,13 De-liang et al14 described their study as removing parts of the arytenoids to reduce the contact of the vocal processes and result in a lower recurrence rate. Thomas et al described that a portion of persistent or idiopathic cases of VPG may result from the underlying glottal insufficiency, and by recognizing and treating glottal incompetence with true vocal fold augmentation, may lead to a shorter surgical treatment course if the conservative measures failed.15 Recent studies showed great advantages of the use of radiation therapy in treating a variety of benign diseases in low dose (total doses in the region of 10–30 Gy).16 The X-ray may depress the reproliferation of lesions after surgery theoretically by preventing the formation of fibroblast cells of the lesion, which lead to tissue exproliferation and the formation of granuloma without affecting would heal in an under fatal dose, for the renovation and cell gathering to the lesion to happen in several hours after operation.17,18 The formation of VPG was a reactive inflammatory response resulting in a benign proliferation of the normal tissues, namely, that which showed similar pathogenesis in other benign proliferation tissues, such as keloid, and other tissues. Therefore, radiation therapy would be effective theoretically in treating VPG.
Yongli Song, et al
Surgical Removal Then Radiotherapy for Refractory VPG
666.e4
height, width, and depth of granuloma. During all this progress, patients were immobilized in foam to target the radiation more accurately to the granuloma region but not to the adjacent tissues.19,20 All lesions were dismissed in the 1–2 months after operation, and no recurrence happened during the follow-up period. The total treatment process lasted for about 2–4 months, which was significantly shorter than the other therapy with higher resolution rate (100%). Two cases complained of light sore throats, who were dismissed 1 month after radiation. No other complications such as dry pharynx, pigmentation of local skin, hoarseness, dyspnea, or even malignancy were observed. However, further collection of possible late side effects with low-dose radiation therapy was needed. Studies of a larger cohort and longer observation were needed to warrant the safety and effectiveness of this treatment.
CONCLUSION This original study demonstrated the effectiveness of surgical removal followed by immediate radiation therapy in the management of refractory VPG. All patients with refractory VPG got the disease resolved in about 2–4 months, which was much shorter than conservative therapy, and no recurrence happened during the next 3–6 years. It might be a promising approach to manage refractory VPG for clinical application, but further studies were needed to warrant the safety and effectiveness.
REFERENCES
FIGURE 2. Laryngoscopic appearance of recurrent laryngeal granuloma involved the left vocal process (A) before treatment and (B) vanished completely 2 months after excision treatment followed by immediate adjuvant radiotherapy.
Criticism had been focused on the complications for radiation therapy in benign diseases because of the damage to normal tissues around the lesions and the possibility of inducing malignancy, as we know. In our study, procedures were carried out with the 3-dimensional conformal radiation system that may help to fix the radiation fields precisely and to minimize the damage around normal tissues. The target radiation fields were located before removing the granuloma, and the targeting information was obtained by measuring the width, height, and depth of the granuloma. Then during the radiation treatment, X-ray beams from several directions precisely matched the
1. Devaney KO, Rinaldo A, Ferlito A. Vocal process granuloma of the larynxrecognition, differential diagnosis and treatment. Oral Oncol. 2005;41: 666–669. 2. Hillel AT, Lin LM, Samlan R, Starmer H, Leahy K, Flint PW. Inhaled triamcinolone with proton pump inhibitor for treatment of vocal process granulomas: a series of 67 granulomas. Ann Otol Rhinol Laryngol. 2010;119: 325–330. 3. Orloff LA, Goldman SN. Vocal fold granuloma: successful treatment with botulinum toxin. Otolaryngol Head Neck Surg. 1999;121:410–413. 4. Maier W, L€ohle E, Welte V. Pathogenetic and therapeutics aspects of contact granuloma. Laryngorhinootologie. 1994;73:488–491. [Article in German]. 5. Massimo C, Roberta P, Alberto S. Postoperative radiotherapy of keloids: a twenty-year experience. Eur J Dermatol. 2002;12:58–62. 6. Davy AO. Laryngeal granuloma, with special reference to cases in Australia. Med J Aust. 1959;46:617–620. 7. Harari PM, Blatchford SJ, Coulthard SW, Cassady JR. Intubation granuloma of the larynx: successful eradication with low-dose radiotherapy. Head Neck. 1991;13:230–233. 8. Mitchell G, Pearson CR, Henk JM, Rhys-Evans P. Excision and low-dose radiotherapy for refractory laryngeal granuloma. J Laryngol Otol. 1998; 112:491–493. 9. Hoffman HT, Overholt E, Karnell M, McCulloch TM. Vocal process granuloma. Head Neck. 2001;23:1061–1074. 10. Rebecca L, Katherine K. Effects of voice therapy on vocal process granuloma: a phonoscopic approach. Am J Otolaryngol. 2005;26: 101–107. 11. Cheng-ping W, Jenq-Yuh K, Yung-Han W, Ya-Ling H, Tzu-Yu H. Vocal process granuloma—a result of long-term observation in 53 patients. Oral Oncol. 2009;45:821–825. 12. Lemos EM, Sennes LU, Imamura R, Tsuji DH. Vocal process granuloma: clinical characterization, treatment and evolution. Braz J Otorhinolaryngol. 2005;71:494–498.
666.e5 13. Damrose EJ, Damrose JF. Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma. J Laryngol Otol. 2008;122:824–828. 14. Huang DL, Zhao H, Liu LF, et al. New surgical method for contact granuloma of larynx. Chin J Otorhinolaryngol Head Neck Surg. 2009;44: 746–748. [Article in Chinese]. 15. Thomas LC, Jackie GS, Melissa MS, et al. Vocal process granuloma and glottal insufficiency: an overlooked etiology? Laryngoscope. 2010;120:114–120. 16. Seegenschmiedt MH. New future for radiation therapy of non-malignant diseases? Radiother Oncol. 2005;74:1–2.
Journal of Voice, Vol. 26, No. 5, 2012 17. Ragoowansi R, Comes PG, Moss AL, Glees JP. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg. 2003;111:1853–1859. 18. Kutzner J, Schneider L, Seegenschmiedt MH. Radiotherapy of keloids. Patterns of care study—results. Strahlenther Onkol. 2003;179:54–58. 19. Jaffray DA. Emergent technologies for 3-dimensional image-guided radiation delivery. Semin Radiat Oncol. 2005;15:208–216. 20. Martin JM, Bayley A, Bristow R, et al. Image guided dose escalated prostate radiotherapy: still room to improve. Radiat Oncol. 2009;4:49–53.
INTRODUCTION Vocal process granuloma (VPG) is an uncommon benign disease that usually develops in the vicinity of the posterior vocal fold, adjacent to the vocal process. It represented a significant treatment challenge because of its tendency to recur irrespective of treatments. The cause of the VPG was not clear yet, although some factors such as hyper functional vocal behaviors, intubation injury, or reflux from the esophagus to the pharynx have been proved to cause or exacerbate the pathology. In recent years, studies had described the benefits of conservative treatments, including voice therapy, antireflux treatments, combined antireflux treatments and voice therapy, or inhaled triamcinolone to certain degree.1,2 More aggressive treatment such as a botulinum toxin injection into vocal process was proved to be a useful adjunctive therapy.3 But all of those therapies would last a relative long period during which patients had to suffer different symptoms and were prone to quit therapy. Surgical excisions were not indicated for the original treatment of VPG for high recurrent rates. It may be indicated to remove obstructive lesions or lesions that cause repetitive throat clearing that perpetuate the disease and to treat the suspected malignancy or refractory diseases ineffective to other therapies.4 But how to
Accepted for publication August 5, 2011. From the *Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China; and the yDepartment of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an, China. Address correspondence and reprint requests to Zhihong Deng, Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, No. 15 Changle Western Road, 710032 Xi’an, China. E-mail: [email protected] Journal of Voice, Vol. 26, No. 5, pp. 666.e1-666.e5 0892-1997/$36.00 Ó 2012 The Voice Foundation doi:10.1016/j.jvoice.2011.08.004
reduce the recurrent rate of the postoperative disease remained a tough problem. Radiation therapy was traditionally applied to treat malignant diseases and recently was reported to be effective in treating benign proliferative diseases in low dose.5 Several studies had showed the benefits of radiation treatment in VPG.6,7 Recently, Mitchell described the favorable prognosis of treating one refractory laryngeal granuloma by excision followed with immediate radiotherapy, which provided us anecdotal experience.8 In this retrospective study, we studied cases with refractory VPG, whose pathology had failed to resolve completely with medical, surgical, or combined surgical-medical treatments. Patients were treated by granuloma excision followed with immediate radiotherapy, and all responded well to our treatments. MATERIALS AND METHODS Patients presented to the ENT department of the Xijing Hospital of the Fourth Military Medical University during January 2004–December 2007 with established VPG were studied. The inclusion criteria for our study were (1) patients with VPG who had been treated routinely with antireflux, voice therapy, surgery, or other therapy before and showed no improvement; (2) patients who suffered sustained symptoms such as hoarseness, chronic cough and/or throat clearing, globus sensation, or dyspnea; and (3) patients who refused persistent conservative treatments. There were 21 patients who enrolled in our study including 16 men and five women, with a mean age of 46.3 years in men, and 44.6 years in women. Causes attributed to the granuloma were believed to be voice abuse (five patients), intubation injury (one patient), chronic reflux (six patients), and
Yongli Song, et al
666.e2
Surgical Removal Then Radiotherapy for Refractory VPG
others unknown (nine patients). All patients with reflux were referred to the specialists and were diagnosed as reflux esophagitis by gastroscopy (Table 1). All patients were counseled about the treatment protocol and informed of possible complications. Five patients refused radiation therapy and accepted operation removal alone, while others were treated with granuloma excision and followed immediate radiotherapy. All operations were carried out under general anesthesia. Granulomas were removed using microsuspension laryngoscope and CO2 laser (6 W, depth in 2 mm, inline modal) with the perichondrium tissues on the surface of arytenoids remaining. All patients were treated with antibiotics for 3 days after operation, and were requested voice rest for at least 2 weeks. Patients were assessed clinically at monthly intervals after the operation, and the laryngoscope was taken for each patient. Complete responders were followed every 3 months for the first 2 years, every 6 months for the next 3 years, and annually thereafter. The radiation fields of the granuloma were precisely conformed in 3-dimensions the day before the operation. Patients started radiation therapy within the following 24 hours after operation. During the treatment, patients were immobilized with a thermoplastic head, neck, and shoulder mask to ensure precisely matching to the granuloma and the reproducibility of the treatments. Patients underwent treatment planning using the Eclipse/Helios treatment planning system with 6-MV photons. Beams were chosen to ensure that more than 95% of the dose encompassed the target region, 3 Gy per day of radiation
was given on 5 days, reaching a total of 15 Gy in 25 fractions, centered on the larynx demonstrated in Figure 1. RESULTS Six patients who refused radiotherapy accepted surgical removal alone, and in five patients recurrence occurred during 2 weeks to 3 months after operation. In the other one, in whom the granuloma was believed to have been caused by intubation injury, no recurrence was observed. All 15 patients who accepted surgical removal followed with radiation therapy presented improvement of voice and release of symptoms soon after operation. During the follow-up period, lesions were dismissed in patients 1–2 months after treatment, and no recurrence was observed (ranging from 3 to 6 years) (Figure 2). Two cases complained of light sore throat that disappeared 1 month after radiation therapy. No other complication, such as flare of local skin or induced malignancy, was observed. DISCUSSION It is considered that the cause of VPG was not clear in many patients although some factors were identified. Reflux might be a primary cause of ulceration and then granuloma formation in the vocal process. Voice abuse and throat clearing might lead to vocal process friction and then cause or exacerbate the pathology. In our study, the causes of the granuloma were believed to be voice abuse (five patients), intubation injury (one patients), chronic reflux (six patients), and others idiopathic,
TABLE 1. Prior Treatments and Duration Antireflux (Months) Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Surgical Excision (n)
PPI
H2A
Speech Therapy
Other Therapy
Recurrent Times
1 2 2 1 3 2 1 1 2 3 2 1 1 1 1 3 1 1 1 3 1
10 8 12 12 24 24 17 6 14 12 9 3 7 11 19 6 12 9 6 12 None
3 3 3 None None 3 None 3 3 3 None None None 3 3 None 3 None None 3 None
Yes No Yes No No Yes No No Yes Yes No No Yes Yes No Yes No No Yes Yes No
Triamcinolone inhaler Triamcinolone inhaler Ciprofloxacin Ciprofloxacin Triamcinolone inhaler Triamcinolone inhaler Triamcinolone inhaler Ciprofloxacin Botulinum toxin injection Ciprofloxacin Triamcinolone inhale Ciprofloxacin Triamcinolone inhaler Botulinum toxin injection Botulinum toxin injection Triamcinolone inhaler Triamcinolone inhaler Botulinum toxin injection Triamcinolone inhaler Ciprofloxacin Triamcinolone inhaler
2 3 3 2 6 4 2 2 3 4 3 3 2 2 2 4 2 3 2 5 2
Abbreviations: PPI, proton pump inhibitor; H2A, H2 antagonist.
666.e3
Journal of Voice, Vol. 26, No. 5, 2012
FIGURE 1. The target radiation field was precisely located with 3-dimensional conformal radiation system, and the targeting information was got in width, height, and depth before radiation therapy. The field circled by the red line was the target radiation field indicated by white arrow.
which were in accordance with earlier studies.9 In the past decades, treatments addressed to get rid of causes for granuloma, such as antireflux treatments and voice therapy, were proved effective (8/10).10 Recently, a study reported that by long-term observation (from 13 weeks to 70 weeks, mean 30.6 weeks), the VPG can be cured at high remission rates (81%) without implementing specific treatments.11 As a result, there remained some patients with diseases, irrespective of treatments; however, in our study, all patients suffered recurrent lesions that had been treated with therapies such as antireflux treatments, voice therapy, or combined treatments before presenting to our department (range from 6 months to 24 months). It may be because of the idiopathic disease that led to its irrespective of treatments or shorter observation term before the remission of the granuloma. Excision of granuloma was not indicated in the original treatment of VPG for the high recurrence rate. It was reported that the recurrence rate was as high as 90% after excision of the granuloma, in a range from 15 to 51 months.4,12 In our study, all patients had recurrent diseases after operation before referring to ours (range from 1 to 3 times), and there were five patients who recurred in six accepted operations alone in about 2 weeks–3 months. Attempts to reduce recurrence rate after operation had been tried, including the new technology, surgical skills, or adjunct therapy. It has been suggested that the type of surgical excision, laser or ‘‘cold steel,’’ may predispose to recurrence, and laser was favored for its ability of precise excision and hemostasis, although it may have reverse thermal effects on
surrounding tissues. Botulinum toxin can temporarily weaken the muscles into which it is injected. Injecting it into the vocal process may reduce the adduction and contact forces at the pathology site, which may eliminate the granuloma and reduce the recurrence after operation, but the effects were not maintained and patients had to suffer hoarseness secondary to the injections.3,13 De-liang et al14 described their study as removing parts of the arytenoids to reduce the contact of the vocal processes and result in a lower recurrence rate. Thomas et al described that a portion of persistent or idiopathic cases of VPG may result from the underlying glottal insufficiency, and by recognizing and treating glottal incompetence with true vocal fold augmentation, may lead to a shorter surgical treatment course if the conservative measures failed.15 Recent studies showed great advantages of the use of radiation therapy in treating a variety of benign diseases in low dose (total doses in the region of 10–30 Gy).16 The X-ray may depress the reproliferation of lesions after surgery theoretically by preventing the formation of fibroblast cells of the lesion, which lead to tissue exproliferation and the formation of granuloma without affecting would heal in an under fatal dose, for the renovation and cell gathering to the lesion to happen in several hours after operation.17,18 The formation of VPG was a reactive inflammatory response resulting in a benign proliferation of the normal tissues, namely, that which showed similar pathogenesis in other benign proliferation tissues, such as keloid, and other tissues. Therefore, radiation therapy would be effective theoretically in treating VPG.
Yongli Song, et al
Surgical Removal Then Radiotherapy for Refractory VPG
666.e4
height, width, and depth of granuloma. During all this progress, patients were immobilized in foam to target the radiation more accurately to the granuloma region but not to the adjacent tissues.19,20 All lesions were dismissed in the 1–2 months after operation, and no recurrence happened during the follow-up period. The total treatment process lasted for about 2–4 months, which was significantly shorter than the other therapy with higher resolution rate (100%). Two cases complained of light sore throats, who were dismissed 1 month after radiation. No other complications such as dry pharynx, pigmentation of local skin, hoarseness, dyspnea, or even malignancy were observed. However, further collection of possible late side effects with low-dose radiation therapy was needed. Studies of a larger cohort and longer observation were needed to warrant the safety and effectiveness of this treatment.
CONCLUSION This original study demonstrated the effectiveness of surgical removal followed by immediate radiation therapy in the management of refractory VPG. All patients with refractory VPG got the disease resolved in about 2–4 months, which was much shorter than conservative therapy, and no recurrence happened during the next 3–6 years. It might be a promising approach to manage refractory VPG for clinical application, but further studies were needed to warrant the safety and effectiveness.
REFERENCES
FIGURE 2. Laryngoscopic appearance of recurrent laryngeal granuloma involved the left vocal process (A) before treatment and (B) vanished completely 2 months after excision treatment followed by immediate adjuvant radiotherapy.
Criticism had been focused on the complications for radiation therapy in benign diseases because of the damage to normal tissues around the lesions and the possibility of inducing malignancy, as we know. In our study, procedures were carried out with the 3-dimensional conformal radiation system that may help to fix the radiation fields precisely and to minimize the damage around normal tissues. The target radiation fields were located before removing the granuloma, and the targeting information was obtained by measuring the width, height, and depth of the granuloma. Then during the radiation treatment, X-ray beams from several directions precisely matched the
1. Devaney KO, Rinaldo A, Ferlito A. Vocal process granuloma of the larynxrecognition, differential diagnosis and treatment. Oral Oncol. 2005;41: 666–669. 2. Hillel AT, Lin LM, Samlan R, Starmer H, Leahy K, Flint PW. Inhaled triamcinolone with proton pump inhibitor for treatment of vocal process granulomas: a series of 67 granulomas. Ann Otol Rhinol Laryngol. 2010;119: 325–330. 3. Orloff LA, Goldman SN. Vocal fold granuloma: successful treatment with botulinum toxin. Otolaryngol Head Neck Surg. 1999;121:410–413. 4. Maier W, L€ohle E, Welte V. Pathogenetic and therapeutics aspects of contact granuloma. Laryngorhinootologie. 1994;73:488–491. [Article in German]. 5. Massimo C, Roberta P, Alberto S. Postoperative radiotherapy of keloids: a twenty-year experience. Eur J Dermatol. 2002;12:58–62. 6. Davy AO. Laryngeal granuloma, with special reference to cases in Australia. Med J Aust. 1959;46:617–620. 7. Harari PM, Blatchford SJ, Coulthard SW, Cassady JR. Intubation granuloma of the larynx: successful eradication with low-dose radiotherapy. Head Neck. 1991;13:230–233. 8. Mitchell G, Pearson CR, Henk JM, Rhys-Evans P. Excision and low-dose radiotherapy for refractory laryngeal granuloma. J Laryngol Otol. 1998; 112:491–493. 9. Hoffman HT, Overholt E, Karnell M, McCulloch TM. Vocal process granuloma. Head Neck. 2001;23:1061–1074. 10. Rebecca L, Katherine K. Effects of voice therapy on vocal process granuloma: a phonoscopic approach. Am J Otolaryngol. 2005;26: 101–107. 11. Cheng-ping W, Jenq-Yuh K, Yung-Han W, Ya-Ling H, Tzu-Yu H. Vocal process granuloma—a result of long-term observation in 53 patients. Oral Oncol. 2009;45:821–825. 12. Lemos EM, Sennes LU, Imamura R, Tsuji DH. Vocal process granuloma: clinical characterization, treatment and evolution. Braz J Otorhinolaryngol. 2005;71:494–498.
666.e5 13. Damrose EJ, Damrose JF. Botulinum toxin as adjunctive therapy in refractory laryngeal granuloma. J Laryngol Otol. 2008;122:824–828. 14. Huang DL, Zhao H, Liu LF, et al. New surgical method for contact granuloma of larynx. Chin J Otorhinolaryngol Head Neck Surg. 2009;44: 746–748. [Article in Chinese]. 15. Thomas LC, Jackie GS, Melissa MS, et al. Vocal process granuloma and glottal insufficiency: an overlooked etiology? Laryngoscope. 2010;120:114–120. 16. Seegenschmiedt MH. New future for radiation therapy of non-malignant diseases? Radiother Oncol. 2005;74:1–2.
Journal of Voice, Vol. 26, No. 5, 2012 17. Ragoowansi R, Comes PG, Moss AL, Glees JP. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg. 2003;111:1853–1859. 18. Kutzner J, Schneider L, Seegenschmiedt MH. Radiotherapy of keloids. Patterns of care study—results. Strahlenther Onkol. 2003;179:54–58. 19. Jaffray DA. Emergent technologies for 3-dimensional image-guided radiation delivery. Semin Radiat Oncol. 2005;15:208–216. 20. Martin JM, Bayley A, Bristow R, et al. Image guided dose escalated prostate radiotherapy: still room to improve. Radiat Oncol. 2009;4:49–53.