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Figure 1.
Long-term Surveillance in the 141 Patients Who Showed Positive Improvement Following Initial Vocal Fold Steroid Injection (VFSI)
Long-term Surveillance in the 141 Patients Who Showed Positive Improvement Following Initial Vocal Fold Steroid Injection (VFSI)

The cumulative incidence rates of symptom recurrence at 6, 12, 18, and 24 months after VFSI were 5%, 8%, 13%, and 19%, respectively. The cumulative incidence rates for receiving secondary interventions at 6, 12, 18, and 24 months were 7%, 10%, 13%, and 17%, respectively. Altogether, the cumulative failure rates (symptom recurrence plus receiving secondary interventions) at 6, 12, 18, and 24 months were 12%, 17%, 24%, and 32%, respectively.

Figure 2.
Subgroup Analyses of Long-term Surveillance in the 141 Patients Who Showed Positive Improvement Following Initial Vocal Fold Steroid Injection (VFSI)
Subgroup Analyses of Long-term Surveillance in the 141 Patients Who Showed Positive Improvement Following Initial Vocal Fold Steroid Injection (VFSI)

After 2 years, patients with mucus-retention cysts showed higher cumulative treatment failure rates (39%) (ie, symptom recurrence or receiving secondary intervention) than did those with polyps (33%) or nodules (31%).

Table.  
Characteristics of Long-term Effectiveness vs Failure in the 141 Patients Who Showed Positive Improvements Following Initial VFSI
Characteristics of Long-term Effectiveness vs Failure in the 141 Patients Who Showed Positive Improvements Following Initial VFSI
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Original Investigation
June 2017

Long-term Surveillance Following Intralesional Steroid Injection for Benign Vocal Fold Lesions

Author Affiliations
  • 1Department of Otolaryngology–Head and Neck Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan
  • 2Department of Otolaryngology–Head and Neck Surgery, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
  • 3Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
JAMA Otolaryngol Head Neck Surg. 2017;143(6):589-594. doi:10.1001/jamaoto.2016.4418
Key Points

Question  Is vocal fold steroid injection (VFSI) a viable option to manage benign vocal lesions?

Findings  Following VFSI, 141 of 189 patients showed positive response (ie, clinically significant symptom resolution without the need for additional procedures) and received long-term surveillance. Two years after the procedure, VFSI remained effective in about half of the initially recruited 189 patients.

Meaning  The effectiveness of VFSI make it viable option for managing benign vocal lesions, but long-term symptom recurrence or subsequent interventions in substantial numbers of patients should be considered in medical decision making.

Abstract

Importance  The short-term outcomes of vocal fold steroid injection (VFSI) are well documented. However, few studies have reported the long-term outcomes following VFSI.

Objective  To investigate the incidence rates of symptom recurrence and secondary interventions following VFSI for benign vocal fold lesions.

Design, Setting, and Participants  This prospective cohort study was conducted at a tertiary referral medical center in Taipei, Taiwan. The cohort included 189 patients with vocal fold lesions who had received VFSI as the primary treatment between August 2011 and September 2013.

Exposures  All participants underwent VFSI.

Main Outcomes and Measures  Long-term surveillance was conducted through structured telephonic interviews and by reviewing medical charts every 6 months over a 2-year period. We assessed the 10-item voice handicap index, dysphonic symptoms, and whether the patients had received any additional interventions after the initial VFSI.

Results  The 189 participants (32 men and 157 women; mean [SD] age, 39 [10] years [range, 20-74 years] included patients who had undergone VFSI for vocal fold nodules (n = 72), polyps (n = 72), or mucus-retention cysts (n = 45). Following VFSI, 141 patients (74.6%; 23 men and 118 women; mean age, 39 years [range, 20-70 years]) showed positive response (ie, clinically significant symptom resolution without the need for additional procedures) and received long-term surveillance. The median follow-up period was 19.4 months, and 2 patients were lost to follow-up postoperatively within 1 year. The cumulative failure rates (subjective symptom recurrence plus secondary treatments) at 6, 12, 18, and 24 months after VFSI were 12%, 17%, 24%, and 32%, respectively. When the initial response rate to VFSI (141 of 189, 74.6%) was considered altogether, VFSI remained effective after 2 years in 50% of the initially recruited 189 patients. The highest rate of long-term effectiveness of VFSI occurred in vocal polyps (54%), followed by nodules (49%) and cysts (43%).

Conclusions and Relevance  This study demonstrates that VFSI can be beneficial in managing benign vocal lesions, especially when first-line treatments are unsuitable. However, the long-term results of this study clarify that a substantial number of patients experience symptom recurrence or receive subsequent interventions within 2 years after VFSI; this should be considered in medical decision making.

Introduction

Benign vocal fold lesions account for the majority of clinical voice disorders, for which the first-line treatment generally involves conservative management such as voice rest and voice therapy through various approaches (eg, hygienic, symptomatic, and physiologic).1 In refractory cases, these treatments are followed by microsurgery.2 With advances in modern endoscopic technology, office-based laryngeal procedures have become an effective treatment modality for various benign laryngeal lesions.3 These procedures have a good patient tolerability,4 high success rates,5 stable perioperative hemodynamic profiles,6 and are cost-effective.7

Direct office-based vocal fold steroid injection (VFSI) was introduced more than 50 years ago8 and has since been used to treat various laryngeal inflammatory diseases9-11 and reduce fibrosis after laryngeal microsurgery.12,13 In recent decades, several studies have reported both subjective and objective improvements after VSFI.14-18 For example, a systematic review and meta-analysis summarized significant improvements in maximum phonation time (MPT) and voice handicap index,19 further supporting VFSI as an alternative treatment for benign vocal lesions.

It is well documented that benign vocal fold lesions are strongly associated with occupational voice overuse,20 environmental factors, and certain psychoemotional characteristics21,22; therefore, recurring lesions following laryngeal procedures are not uncommon.23 However, only sporadic cases of recurrence following VFSI have been reported 6 to 9 months after treatment.15 To further delineate the clinical role of VFSI, the present study investigated the incidence rates of symptom recurrence and secondary intervention following VFSI, which are not well documented in the literature.

Methods
Study Participants

This study prospectively recruited patients with vocal nodules, polyps, and mucus-retention cysts who received VFSI between August 2011 and September 2013. Clinical diagnoses were based on the appearance of the vocal fold edge and the vibratory property revealed by videolaryngostroboscopy. Vocal fold nodules refer to bilateral epithelial thickening or swelling, usually at the junction of the anterior to middle third of the vocal folds. Vocal fold polyps refer to unilateral, focal accumulation of translucent or hemorrhagic stroma within the superficial lamina propria. Mucus retention cysts of the vocal fold refer to subepithelial, translucent-to-yellowish, fluid-filled mass that mostly cause significant reduction or absence of mucosal wave.24

All patients completed a detailed questionnaire during the first clinical visit. The collected data included age, sex, duration of dysphonia, smoking status, and alcohol consumption as well as the 10-item voice handicap index (VHI-10)25,26 and reflux symptom index.27 We measured MPT during the initial clinical visit by instructing the patient to produce the /a:/ sound for as long as possible after deep inspiration and at a spontaneous, comfortable pitch and loudness level for 3 successive trials. Perceptual evaluation of voice quality was also rated during the first clinical visit by consensus between 2 authors (C.-T.W. and P.-W.C.) using the grade, roughness, breathiness (GRB) scale: 0, normal; 1, slightly deviated; 2, moderately deviated; and 3, extremely deviated.28 Occupational demands of the voice were classified as (1) professional (ie, singer, actor/actress, radio broadcaster, and/or singing student), (2) high (ie, teacher, clergy, lecturer, salesperson, tour guide, aerobic exercise coach, and/or person who works in a noisy environment), or (3) routine (others), as suggested in the literature.29

Vocal Fold Steroid Injection

According to our routine practice, VFSI is provided as an alternative to standard management in the following scenarios. For vocal fold nodules, VFSI is performed when patients cannot comply with voice conservation or experience fair response after vocal hygiene education or voice therapy. For vocal polyps and cysts, VFSI was applied as an alternative when microsurgery was not suitable (eg, trismus, cervical spine disorder, high risk for general anesthesia) or was refused by the patients. All patients made their own decisions to undergo, and provided written informed consent for, VFSI. The study was approved by the research ethics review committee of Far Eastern Memorial Hospital, Taipei, Taiwan, waiving written informed consent for study participation.

The VFSI procedure was performed under local anesthesia in office settings. The patient was instructed to pull out and hold the tongue, while the surgeon used his or her nondominant hand to operate the rigid laryngoscope. Under visual guidance, a 0.1-mL, 1:1 mixture of triamcinolone acetonide (10 mg/mL) and dexamethasone sodium phosphate (5 mg/mL) was injected into the Reinke space of the vocal fold lesions using a curved injection needle (Model 16-50050, Medtronix, Xomed).30 For patients who were intolerant of this transoral procedure, transnasal injection via the working channel of a flexible nasopharyngoscope was applied with an endoscopic injection apparatus (Olympus NM-101C-0427), which included a reusable metallic external sheath (MAJ-655) and a disposable flexible needle tract with a 27G rigid tip (MAJ-656).31 According to our clinical experience, the intolerance rate for either transoral or transnasal injection was approximately 3% (unpublished data). All patients received postoperative voice rest for 3 days.

Outcome Evaluation

A total of 189 patients received VFSI during the study period. Surveillance of long-term effectiveness was conducted in the 141 patients who showed positive response following the initial VFSI. We carefully reviewed the patients’ medical records during all follow-up clinic visits—in particular, their VHI-10 scores, presence of recurring symptoms, and the dates of subsequent procedures (eg, repeat VFSI, in-office laser procedures, or phonomicrosurgery). For patients who did not maintain a regular clinical follow-up schedule, we conducted structured telephonic interviews every 6 months for up to 2 years. All patients were asked the 10 questions of the VHI-10 and whether the patient had received any additional interventions. Symptom recurrence was defined using a subjective report together with a VHI-10 score of more than 10.26

Statistical Analysis

The study applied time-to-event analysis and the Kaplan-Meier method to analyze the cumulative incidence rates for symptom recurrence and secondary interventions in the 141 patients receiving long-term surveillance. Patients without symptom recurrence or secondary intervention were censored at the last clinical visit or telephonic interview. The overall effective rate among the initially recruited 189 patients was computed by multiplying the success rates obtained from the Kaplan-Meier method and the initial response rate to VFSI. Effect sizes and the corresponding 95% confidence interval (CIs) were provided to examine the differences of demographic factors and disease severity between the long-term effective and ineffective groups. All statistical analyses were conducted by SAS software, version 9.3 (SAS Institute Inc) and R software (version 3.3.1, R Foundation).

Results

This study prospectively recruited 189 consecutive patients receiving VFSI, including 157 female and 32 male patients. The mean (SD) age was 39 (10) years and ranged from 20 to 74 years. Vocal nodules were diagnosed in 72 patients, polyps in 72, and mucus-retention cysts in 45 patients. Following VFSI, 141 patients (74.6%) showed positive response to VFSI (ie, clinically significant symptom resolution without the need for any additional procedures), whereas the other 48 patients (25.4%) reported no improvement following VFSI. The response rates of initial VFSI among the 3 diagnostic groups were 71% for nodules, 81% for polyps, and 71% for mucus-retention cysts.

Long-term surveillance was conducted in the 141 cases that showed positive improvement after initial VFSI, while the other 48 cases were not followed up regularly, according to our original study design. The median follow-up period was 19.4 months (eTable 1 in the Supplement). Two patients were lost to follow-up within 1 year following VFSI (at 1.1 and 4.6 months, respectively). During the follow-up period, dysphonic symptoms recurred in 20 patients at a median interval of 11 months from the initial VFSI. The cumulative incidence rates for symptom recurrence at 6, 12, 18, and 24 months were 5%, 8%, 13%, and 19%, respectively (Figure 1, Kaplan-Meier method). In addition, another 20 patients received secondary interventions at a median interval of 4 months from the initial VFSI (repeated VFSI in 13 cases, angiolytic laser in 1 case, and phonomicrosurgery in 6). The cumulative incidence rates for receiving secondary interventions at 6, 12, 18, and 24 months were 7%, 10%, 13%, and 17%, respectively (Figure 1). Combing the results of symptom recurrence and secondary interventions, the cumulative failure rates at 6, 12, 18, and 24 months were 12%, 17%, 24%, and 32%, respectively (Figure 1) (see also eTable 2 in the Supplement). Considering the immediate response rates to VFSI (74.6%, 141 of 189 patients) and the long-term results for symptom recurrence and secondary intervention, we deduced that VFSI remained effective for 66% of patients after 6 months. This number gradually decreased to 62% after 12 months, 57% after 18 months, and 50% after 24 months.

Subgroup analyses revealed that patients with mucus-retention cysts had higher 2-year cumulative rates of symptom recurrence or secondary intervention following the initial VFSI (39%), than did those with polyps (33%) and nodules (31%), but the differences were nonsignificant (Figure 2). Combining the initial response rates to VFSI and the results from subsequent long-term surveillance, we deduced that VFSI remained effective after 2 years in 54% of patients with vocal polyps, followed by 49% and 43% in patients with nodules and cysts, respectively.

To investigate factors that may cause predisposition to symptom recurrence or receiving secondary intervention during the long-term follow-up, we compared the demographic factors and disease severity among the 141 patients who showed immediate improvements following the initial VFSI. The comparison revealed that the demographic distributions, including age, sex, symptomatic duration, cigarette smoking, alcohol consumption, reflux symptom index, and occupational vocal demand were similar between the 2 groups (Table). In addition, we found that patients with long-term VFSI effectiveness presented with a higher MPT than did those in whom the VFSI was not effective in the long term (Table). Other parameters, including VHI-10 and perceptual voice quality (ie, GRB scores) were similar in these 2 groups.

Discussion

Yanagihara et al8 first proposed VFSI by indirect mirror laryngoscopy in 1962 and reported effectiveness of 62.5% and 79.6% when using prednisolone and dexamethasone, respectively. However, VFSI as an office-based alternative procedure to treat benign vocal fold disorders had not been widely adopted until the past decade, when 2 major refinements to the procedure were made: (1) enhanced precision of needle placement by using flexible fiberscope guidance and (2) the use of triamcinolone, a depot solution with a longer effective duration.32 In the pilot series reported by Tateya et al,14,32 VFSI resulted in symptom improvement in more than 90% of the patients with Reinke edema and vocal nodules. Later, Mortenson and Woo16 reported on 34 patients with nodules, polyps, cysts, granuloma, and scars who were treated successfully by using intracordal methylprednisolone injection. The authors suggested that office-based steroid injection in the vocal folds can be helpful to (1) avoid or delay phonosurgery, (2) reduce scarring following microsurgery, and (3) reduce edema and granulation. Subsequent studies have further supported the alternative application of VFSI to treat benign vocal lesions by providing more objective measurements (eg, aerodynamic and acoustic analyses).15,17,18

An abundance of related data on the effectiveness of VFSI is available in the literature, but most studies are based on a pretest-posttest design that includes only 1 treatment group, neglecting the possibility of spontaneous lesion regression following voice conservation or phonation habit modification. Therefore, our group conducted a comparative study and found a significantly higher lesion regression rate in VFSI compared with that after only vocal hygiene education.30 Potential adverse effects of VFSI have also been reported in a recent series, in which the incidence rates for vocal fold hematoma, deposition of triamcinolone, and vocal fold atrophy were 20%, 4%, and 1%, respectively.33

Considering that most benign vocal lesions result from phonotrauma, it has been proposed that VFSI might take effect via decreasing cellular permeability,34 down-regulation of proinflammatory cytokines,35 decreasing rates and amounts of collagen deposition during the healing process,36 and reducing fibroblast proliferation and transforming growth factor β (TGF-β)–induced collagen synthesis.37 In this study, 74.6% of patients (141 of 189) responded well 1 month after VFSI (ie, clinically significant symptom resolution without the need for any additional procedures), which is consistent with the literature.15,17,18,33 However, because most benign vocal lesions arise from underlying voice overuse or misuse, symptom recurrence or necessity for additional procedures were expected. Lesion recurrence rates of 4% to 31% over a wide range of follow-up periods have been reported in the literature (from 4 weeks to 24 months after VFSI).15,17,18,32,38 Without a clear follow-up protocol and predefined criteria for recurrence, these data on symptom recurrence following VFSI might be hard to interpret or may be subject to bias.

Understanding symptom recurrence and the need for secondary intervention is crucial to clearly defining the possible clinical role of VFSI. If VFSI can result in long-term symptomatic control, it could be added to the list of management options. Otherwise, VFSI might only be considered an alternative when standard treatment has failed or is not suitable. To overcome the limitation of the inconsistently reported recurrence rates in the literature, we enforced a stringent follow-up protocol on the prospective cohort. By maintaining a regular timetable for telephonic interviews (every 6 months for up to 2 years), this study achieved a high follow-up rate (98%) in the 141 patients who showed clinically significant improvement after initial VFSI, with only 2 patients lost to follow-up within 1 year. In addition, predefined criteria for treatment failure, established using the well-validated VHI-10 questionnaire as well as clear documentation of secondary interventions, provided reliable results that VFSI as the primary treatment for vocal nodules, polyps, and mucus-retention cysts remained effective in 50% of patients after 24 months.

The treatment efficacy of voice therapy for vocal nodules is well established1,39; however, the clinical effectiveness of voice therapy may occasionally be hampered by other factors such as patient adherence.40 Because intracordal steroid injection is fast-acting (usually 3-7 days), and its potential adverse effects are self-limited,33 we propose that VFSI might be provided as an adjuvant option for patients who cannot comply with, or who show minimal improvement after, conservative managements or for patients who desire rapid symptom resolution (eg, teachers during a semester). Nevertheless, patients should always be reminded of the fundamental role of postoperative voice therapy to avoid lesion recurrence.23

Although most clinicians agree that microsurgery is indicated for vocal fold polyps and cysts, little has been reported on the long-term recurrence rates. In the present study, we found that VFSI remained effective after 2 years in 54% and 43% of patients with vocal fold polyps and cysts, respectively, considerably lower than that estimated following microsurgery.41,42 Hence, we believe that surgical dissection of vocal polyps and cysts remains the definitive treatment of choice. Nevertheless, in patients with concerns regarding the risk of general anesthesia, patients in whom direct suspension laryngoscopy may be difficult (eg, patients with trismus), and in patients who refuse surgery, VFSI could be used to temporarily relieve dysphonic symptoms. In addition, patients should be informed preoperatively that the duration of treatment effects could vary and that additional interventions may be required.

In the present study, patients in whom VFSI remained effective after 2 years tended to present with a longer MPT, which can be considered a proxy of the efficiency of energy transmission from the transglottic pressure gradient to the periodic open-close of vocal fold vibration.43 Therefore, we suspect that patients with lower MPT might use inadequate respiratory strategies (eg, insufficient inspiration and forced expiration), predisposing them to the failure of maintaining the treatment effects, as mentioned in a recent study.44 Other demographic factors, such as occupational vocal demand, did not reveal significant differences between the long-term effective and ineffective cases, which might be related to insufficient subgroup case numbers and the resulting small effect size.

Limitations

The major limitation of this study is the lack of continual follow-up laryngeal endoscopies after VFSI, which may provide more objective results regarding lesion recurrence rather than symptom recurrence. However, such a study protocol may face difficulties in ensuring patient follow-up. Because most benign vocal lesions primarily affect patient quality of life,45 any treatment of these benign lesions should focus on relieving patient discomfort and is best initiated by the patient.46 Therefore, subjective reporting of recurring dysphonia and inquiring for subsequent intervention should be interpreted to more accurately reflect the clinical disease burden. Moreover, the alternative use of VHI-10 through telephone survey from the treating institution is not the traditional use,25 and may represent another source of potential bias. In addition, nonblinded rating of voice quality (ie, the GRB scores) could also result in potential bias. Nevertheless, considering that all ratings were obtained during the first clinical visit (ie, before VFSI), the study results should be mostly reliable.

Another limitation of this study was the follow-up period. Because most benign vocal fold disorders are closely associated with personal phonation behavior and occupational voice loads, a longer follow-up period may yield higher recurrence rates. Furthermore, the lack of follow-up records in the 48 patients who did not benefit from the first steroid injection prevented the comparison of recurrence rates between different clinical scenarios. Finally, despite the patient cohort for this study being probably among the largest that has been reported thus far, the number of patients may still be inadequate for ensuring strength of the subgroup analyses, such as the differences between the 3 diagnostic groups (Figure 2).

Conclusions

When first-line treatments are unsuitable, VFSI can be applied as an alternative treatment for vocal nodules, polyps, and mucus-retention cysts. However, both clinicians and patients should be made aware that VFSI may not always be effective in the long term. Our results show that symptom recurrence and the need for secondary interventions after VFSI are not uncommon within 2 years of the initial VFSI.

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Article Information

Accepted for Publication: November 23, 2016.

Corresponding Author: Chi-Te Wang, MD, PhD, Department of Otolaryngology–Head and Neck Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan, No. 21, Section 2, Nan-Ya South Road, Ban Chiao Dist, New Taipei City, Taiwan (drwangct@gmail.com).

Published Online: March 23, 2017. doi:10.1001/jamaoto.2016.4418

Author Contributions: Dr Wang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Wang, Lai.

Acquisition, analysis, or interpretation of data: Wang, Cheng.

Drafting of the manuscript: Wang.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Wang.

Obtained funding: Wang, Cheng.

Administrative, technical, or material support: Wang, Cheng.

Study supervision: Lai.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. No disclosures were reported.

Funding/Support: This study was supported by research grants from Far Eastern Memorial Hospital (FEMH-2015-C-027) and from the National Science Council (MOST 104-2314-B-418-013), Taipei, Taiwan.

Role of the Funder/Sponsor: The funding institutions had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Previous Presentation: This study was presented at the Fall Voice Conference; October 15-17, 2015; Pittsburgh, Pennsylvania.

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