病灶內類固醇注射用於治療良性聲帶病變: 比較性效果與成果研究

Intralesional Steroid Injection for Benign Vocal Fold Lesions: Comparative Effectiveness and Outcome Researches

王棨德(Chi-Te Wang)

指導教授 ： 賴美淑

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2014年)

https://doi.org/10.6342/NTU.2014.02244

摘要

目的:本論文應用臨床流行病學之研究方法，探討聲帶類固醇注射於良性聲帶病變之治療成果。主要之研究方向包括:1)比較聲帶類固醇注射與保守治療(嗓音保健與衛教)、侵入性治療(喉顯微手術)之優劣與臨床應用時機；2)多面向研究聲帶類固醇注射用於治療良性聲帶病變之成果與可能之預後因子、副作用發生率及其危險因子、以及治療後之長期成效追蹤。

方法:本研究收錄自2009年1月至2013年12月間就診並接受治療之良性聲帶病變患者。所有患者均於初診時記錄相關之嗓音症狀、抽菸喝酒習慣、職業與用聲程度、其他內科疾病，並填寫10項聲音障礙指標(voice handicap index, VHI-10)與胃酸逆流症狀量表(reflux symptom index, RSI)。治療成果於治療後1及 2個月間進行測量，項目包括喉閃頻內視鏡檢查、聽覺音質評估(使用GRB量表)，電腦化嗓音分析、以及病患主觀評分（0-10分）。聲帶類固醇注射於門診局部麻醉下以經口或經鼻內視鏡進行治療，定義術後VHI-10<=10分，或GRB<=1分為治療成功，並藉由單變項與多變項分析探討相關之預後因子與發生副作用之可能危險因子。治療後之長期成效則依據病歷記載及每半年電話追蹤之結果，將症狀復發且VHI-10 ＞10分，或接受後續治療者定義為治療失敗。

結果:相較於保守治療，聲帶類固醇注射於治療後1、2個月皆有較佳之成效(p 值<0.05)。對聲帶結節之患者而言，聲帶注射之效果在術後1個月比音聲衛教好(p 值<0.05)；至於聲帶息肉之患者，接受聲帶注射後1個月及2個月，病灶皆顯著變小(p 值<0.01)，但接受音聲衛教的組別則沒有明顯改善。對於聲帶息肉或黏液囊腫之病患，接受聲帶類固醇注射或喉顯微手術後皆有顯著之進步，惟男性、有抽菸喝酒習慣、病灶較大、出血性息肉、嗓音品質較差等患者多傾向接受顯微手術。在應用propensity score移除極端值之後，比較兩種治療方式顯示喉顯微手術在治療聲帶息肉與囊腫上仍有較佳之成效(p 值<0.05)。
雖然聲帶類固醇注射可有效應用於治療聲帶結節、息肉、與黏液囊腫，但礙於收案數之限制，對於黏膜下水腫(Reinke’s edema), 皮下纖維組織增生(fibrous mass)與偽囊腫(pseudocyst)之治療成效並不明確。接受經鼻內視鏡治療之患者之不適感較經口治療來的高(p 值=0.01)，但兩者之治療成效則無顯著差異。職業上頻繁用聲與纖維化之”硬”結節，在接受聲帶類固醇注射後之臨床治療成效較差(p 值<0.05)。聲帶息肉之患者如嗓音症狀大於一年或同時合併有胃食道逆流，接受聲帶類固醇注射後之臨床成效較差(p 值<0.05)。治療後常見之副作用包括局部出血(27%)、藥物沉積(4%)、與聲帶萎縮(1%)，於1-2個月內可自行恢復，無不可逆之後遺症。其中，聲帶微血管異常與用聲程度較高之患者，較易於治療後發生聲帶出血之症狀。
長期追蹤顯示接受聲帶類固醇注射兩年內，有28% 之個案症狀復發或接受後續治療，聲帶結節、息肉、囊腫之治療失效比率並無明顯差異。後續分析顯示，病患自覺症狀較嚴重者，治療失效之比率較高(p 值<0.01)。對於聲帶結節與囊腫之患者，症狀發生一年以上始就醫之患者，治療後失效之比率較低 (p 值<0.05)。

結論: 聲帶類固醇注射可有效應用於聲帶結節、息肉、與黏液囊腫。對於聲帶結節之患者，聲帶類固醇注射可較快達成臨床成效；對於息肉與囊腫，則仍以喉顯微手術之成效較佳。職業用聲程度、結節軟硬度、病程長短、與胃食道逆流皆會影響聲帶類固醇注射之治療成果。治療後之副作用包括局部出血、藥物沉積、與聲帶萎縮，於1-2個月內可自行恢復。聲帶類固醇注射後症狀復發或需要後續治療之情況並不罕見，有賴後續研究探索個人之行為與心理因素之潛在關聯性與影響。

關鍵字

聲帶結節 ； 息肉 ； 囊腫 ； 喉顯微手術 ； 胃食道逆流 ； 嗓音 ； 職業

並列摘要

Objective: This thesis conducted series of epidemiological studies focusing on the application of vocal fold steroid injection (VFSI) for treating benign vocal fold lesions. First, we compared the clinical effectiveness of VFSI with non-invasive intervention (i.e. vocal hygiene education, VHE) and invasive procedure (i.e. phonomicrosurgery). Additionally, we investigated treatment outcomes, including prognostic factors, side effects, and long-term surveillance of treatment failures following VFSI.

Methods: This study recruited patients with benign vocal fold lesions treated from January 2009 to December 2013. A detailed history was recorded using a self-completing questionnaire, including age, gender, duration of symptoms, smoking, alcohol consumption, occupational vocal demand, medical comorbidity, 10-item voice handicap index (VHI-10), and reflux symptom index (RSI).
VFSI was performed under local anesthesia in the office setting through trans-oral or trans-nasal approaches. Treatment outcomes were evaluated 1 and 2 months after the procedure, including endoscopic evaluation of lesion regression and vibratory capacity of vocal folds, perceptual voice quality (GRB: grade, roughness, and breathiness), acoustic analysis, and 10-item voice handicap index (VHI-10). “Responder” of VFSI was defined by: 1) post-operative VHI-10 score <=10 points or 2) GRB score <=1 point. Prognostic factors for VFSI treatment outcomes and risk factors for side effects following VFSI were evaluated via univariate and multivariate analyses. Long-term treatment results were investigated by reviewing medical charts and structured telephone interviews semi-annually. Treatment failure after VFSI was defined as 1) subjective report of recurring dysphonic symptoms with VHI-10 score more than 10 points or 2) receiving secondary procedures.

Results: Compared with vocal hygiene education (VHE), VFSI was associated with a higher lesion reduction rate (p<0.05). In vocal nodules, VFSI achieved a higher lesion regression rate than VHE at 1 month (p<0.05). In vocal polyps, the lesion reduction rate after VFSI was higher than that following VHE at 1 and 2 months (p<0.01). Crude treatment outcomes measured at 1 and 2 months demonstrated significant improvements from baseline following both VFSI and phonomicrosurgery for vocal polyps and cysts. Male, smokers, patients with larger or hemorrhagic vocal polyps and worse voice quality tended to receive phonomicrosurgery. After controlling baseline heterogeneity by trimming patients with extreme propensity scores, phonomicrosurgery remains more effective than VFSI in patients with both vocal polyps and cysts.
Although treatment outcomes of VFSI in patients with vocal nodules, polyp and mucus retention cysts revealed significant improvements from baseline, the treatment outcomes for Reinke’s edema, fibrous mass and pseudocyst were unclear. Higher occupational vocal demands and fibrotic vocal nodules were significantly associated with poorer clinical responses as measured by the VHI-10 and GRB scores, respectively. For vocal polyps, dysphonia for more than 1 year was significantly associated with lower VHI-10 scores, whereas patients with laryngopharyngeal reflux (LPR) showed significantly poor postoperative voice quality. Trans-oral and trans-nasal injection approaches revealed similar treatment results, whereas more discomforts were experienced during trans-nasal approach (p=0.01). Side effects following VFSI included hematoma (27%), triamcinolone deposits (4%), and vocal atrophy (1%), which resolved spontaneously within 1-2 months. Presentation with vocal fold ectasias/varicosities and higher vocal demands were significantly correlated with postoperative vocal hematoma.
Long-term survey demonstrated the cumulative failure rates (symptomatic recurrence plus secondary treatment) following VFSI were 28% (for up to 24 months), without significant difference between vocal nodules, polyp and cyst. Time-to-event analysis documented that patients with higher subjective disease severity were significantly associated with more treatment failures after VFSI (p<0.01). Prognostic analyses noted that longer symptoms durations (> 12 months) tended to present with less treatment failures after VFSI, for vocal nodules and cysts (p<0.05).

Conclusions: VFSI was effective for vocal nodules, polyp and cysts. Comparative effectiveness researches demonstrated that VFSI resulted in more rapid lesion regression than subjects receiving vocal hygiene education in vocal nodules, whereas phonomicrosurgery remains more effective than VFSI in patients of vocal polyps and cysts. Occupational vocal demand, subtypes of vocal nodules, chronicity of clinical symptoms, and the presence of LPR were potential prognostic factors for short-term treatment outcomes of VFSI. Side effects following VFSI were self-limited, including vocal hematoma, triamcinolone deposits, and vocal atrophy. Treatment failure after VFSI were not infrequent, which necessitate further study to explore the potential influence of personal behavioral and psycho-emotional factors on benign vocal lesions.

並列關鍵字

nodules ； polyp ； cyst ； triamcinolone ； dexamethasone ； laryngopharyngeal reflux ； voice ； occupation

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