Indole-3-Carbinol for recurrent respiratory papillomatosis: long-term results

We report the results of a clinical study using Indole-3-Carbinol (I3C) for the treatment of recurrent respiratory papillomatosis (RRP). I3C is abundant in cruciferous vegetables and has been shown to decrease papillomatous growth in cell cultures and be effective in an animal model of RRP. This is a prospective, open-label study design. Patients with RRP were enrolled from September 1996 to August 2001 and treated with I3C (adult dose of 200 mg PO BID). All patients underwent complete surgical removal and then started I3C. Further surgery was performed on an as-needed basis. Patients were categorized as having a complete, partial, or no response to I3C. Thirty-three patients treated with I3C were available for long-term follow-up (mean=4.8 years), whereas 12 patients were lost to follow-up. Eleven (33%) patients experienced remission of papillomatous growth and did not require surgery while on I3C. Ten (30%) patients had a reduction in papillomatous growth that resulted in less frequent surgery. Twelve patients (36%) had no clinical response. No patients experienced a worsening of their RRP. Of the 9 pediatric patients available, 1 experienced a complete response, 3 a partial response, and 5 had no response to I3C. Twelve patients with a positive response (partial or complete) to I3C are still taking I3C. Seven positive responders discontinued I3C, 3 of which have remained disease-free, whereas 4 continue to have RRP. No immediate or long-term side effects related to I3C were found. I3C has been found to be a successful treatment option for RRP. I3C's efficacy in pediatric patients merits further study.     

Treatment of laryngeal contact ulcers and granulomas: A 12-year retrospective analysis

Multiple etiological factors including gastroesophageal reflux, hyperfunctional voice use, and endotracheal intubation have been implicated in the development of posterior laryngeal ulcers and granulomas. The optimal approach to treatment of these lesions remains controversial. The mainstay of treatment at Vancouver General Hospital has been aggressive medical management of gastroesophageal reflux, with complimentary voice therapy offered to patients suspected of having significant hyperfunctional phonation. The authors reserve Botulinum toxin injection or surgical excision for patients who fail initial therapy. They conducted a retrospective analysis of their voice clinic records from 1985–1997 to examine the efficacy of this approach. They identified 76 patients with the diagnosis of contact ulcer or granuloma. Fifty-two patients had follow-up data available for review. Ninety-four percent of patients were treated nonsurgically: 35 patients were treated solely by dietary and medical therapy to control gastroesphageal reflux, 10 patients were treated by a combination of medical gastroesophageal reflux control and voice therapy, 3 patients had Botox injections, 2 patients had surgical excision of granuloma, 1 patient had a Kenalog injection, and 1 patient underwent laparoscopic fundoplication. Overall, 77% of patients had complete resolution, whereas 11% had partial resolution and another 11% had no significant improvement. The data supports control of gastroesophageal reflux as a central component in treatment of posterior laryngeal ulcers and granulomas.     

Unilateral Versus Bilateral Injections of Botulinum Toxin in Patients with Adductor Spasmodic Dysphonia

Both unilateral and bilateral thyroarytenoid muscle injections of Botox provide effective management of voice symptoms in patients with adductor spasmodic dysphonia; however, the preferred injection technique has not been established. In this study, 16 patients were treated with unilateral injections (72 injections total) and 33 patients were managed with bilateral injections (133 injections total). Individual assignments to injection type were based on treatment previously received and dose was adjusted according to the patient's previous treatment response. An optimal treatment included a benefit lasting 3 months or more with side effects lasting 2 weeks or less. Compared to patients receiving bilateral injections, those receiving unilateral injections more frequently noted a benefit of 3 months or more (p = 0.03), side effects of 2 weeks or less duration (p = 0.03), as well as both a 3-month benefit and a 2-week or less side effect (p = 0.0004). Injection type had no effect on optimal Botox dosing with repeat injections. Successive unilateral injections at the same dose were more likely (p = 0.012) than successive bilateral injections to produce the same or longer duration of benefit. We conclude that a unilateral injection routine has a more optimal and consistent treatment effect/side effect profile.     

Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis

Mitomycin-C is an antineoplastic antibiotic that acts as an alkylating agent by inhibiting DNA and protein synthesis. It can inhibit cell division, protein synthesis, and fibroblast proliferation. The purpose of this pilot study is to investigate intraoperative applications of topical mitomycin-C in treatment and prevention of glottic and subglottic stenosis. Eight patients with posterior glottic and/or subglottic stenosis were treated with endoscopic CO2 laser excision followed by topical application of 0.5 cc of 0.4 mg mitomycin-C per milliliter of saline for 4 minutes at the surgical site. After mean follow-up of 15 months (10-20) all patients had clinical improvement of their airway and resolution of their preoperative symptoms. No complications were noted in this study. Although a longer follow-up and further controlled studies are needed, the use of topical mitomycin-C may prove useful in the treatment and prevention of subsequent restenosis and scar formation in the larynx and trachea.     

The effect of patient factors on response outcomes toBotox treatment of spasmodic dysphonia

Injection of botulinum toxin (Botox) into the laryngeal muscleshas become the treatment of choice for controlling the symptoms of spasmodic dysphonia (SD). Currently, no specific battery of objective tests to assess the outcome is universally accepted. The purpose of this study was to investigate demographic, clinical, and treatment factors with voice outcome following Botox injection. Sixty-eight patients with adductor SD who underwent at least one Botox injection during a 5-year period were studied. Voice outcome measures were made from patient self-reporting scales and included overall vocal quality, length of response, and duration of breathiness. Vocal quality was significantly correlated with the underlying severity of vocal symptoms prior to treatment, incidence of breathiness and unilateral versus bilateral injection. The length of response was greater in males and following bilateral injections. An increased period of breathiness significantly correlated with bilateral injections.     

A comparison of injection techniques using botulinum toxin injection for treatment of the spasmodic dysphonias

The benefit duration and side effects following effective treatment of spasmodic dysphonia or voice tremor using botulinum toxin injection were studied following 477 open trial unilateral or bilateral injections provided to 178 patients. A comparison of unilateral and bilateral injections in male and female patients with adductor spasmodic dysphonia demonstrated an increased benefit duration following unilateral injections in women, longer periods of breathiness in men than in women following bilateral or unilateral injections, and a trend for reduced benefit durations following repeated treatments using bilateral injections. Outcomes were similar in the adductor spasmodic dysphonia and vocal tremor groups following thyroarytenoid injection while benefit durations were reduced and side effects lasted longer in patients with abductor spasmodic dysphonia following cricothyroid injections. Long-term benefit > 1 year occurred in 12.3% of patients following injection.     

Longitudinal Effects of Botulinum Toxin Injections on Voice-Related Quality of Life (V-RQOL) for Patients with Adductory Spasmodic Dysphonia

Adductory spasmodic dysphonia is a focal dystonia of laryngeal muscles. Patients with this disorder typically have severe vocal difficulties, with significant functional, social, and emotional consequences. There is no widely accepted cure for this condition, however, botulinum toxin injections of the thyroarytenoid muscles are considered by most voice clinicians to be the state of the art treatment. Based on extensive experience treating patients for adductory spasmodic dysphonia, we feel that traditional means of voice assessment do not adequately measure either the disease severity or the treatment outcomes. That is, listening to or acoustically analyzing limited phonatory samples does not capture the functional, social, and emotional consequences of this disorder. These consequences will be reflected in a patient's voice-related quality of life (V-RQOL). Using a validated voice outcomes instrument, the V-RQOL Measure, the purpose of this study was to quantify longitudinal changes in the V-RQOL of patients with adductory spasmodic dysphonia who are undergoing botulinum toxin injections. Twenty-seven consecutive new patients presenting with dysphonia to our institution during an 18-month period were diagnosed with adductory spasmodic dysphonia, and treated patients were evaluated prospectively using the V-RQOL Measure. Results indicated that (1) V-RQOL was initially very low for these patients, (2) botulinum toxin injections improved it significantly for each injection cycle studied, and (3) the magnitude of the treatment effect appears to change across injections.     

Voice Therapy Outcome—A Randomized Clinical Trial Comparing Individual Voice Therapy,Therapy in Group,and Controls Without Therapy

ObjectiveA stumbling-block in voice therapy is how the patient will be able to apply the new voice technique in everyday life. Possibly this generalization process could be facilitated by giving voice therapy in group because of the natural forum for training voice-to-speech early in communication between the patients in a group setting. The aim of the study was to compare treatment results from individual voice therapy and voice therapy in group, at several time points and in comparison to patients with no voice therapy.MethodsA randomized treatment study was performed with 77 consecutive patients diagnosed with a functional voice disorder. Thirty-one patients were randomized to individual and group therapy, respectively, and 15 patients to no therapy. The assessments included standardized voice recording and registration of voice range profile (VRP), answering Voice handicap index (VHI) and visual analogue scales for self-hoarseness and self-vocal fatigue, and perceptual voice evaluation by speech-language pathologist. The assessments were performed before, direct after therapy, and three months later in all groups. The 2 therapy groups were also assessed 12 months after therapy.ResultsAll VHI scores as well as the self-ratings of hoarseness and vocal fatigue, and the perceptual evaluation of voice quality and maximum VRP improved significantly in both therapy groups 3 months after treatment and at 12 months follow-up. There were no significant changes in the control group, with the exception of decreased self-rated hoarseness and increased maximum VRP. Comparisons between treatment groups showed significant larger improvement after group therapy for VHI physical subscale at 12 months, as well as significant lower VHI total score at all measurement sessions and lower subscale scores at 12 months. There were no differences between treatment groups in self-hoarseness or self-vocal fatigue and no difference in perceptual voice quality or VRP. Comparison between controls and treatment groups showed significant larger change in treatment groups from baseline to three months in VHI total and to end of therapy in functional subscale. Treatment groups also showed significant lower scores than controls at each measurement session, for VHI total and physical subscale as well as lower degree of perceptual aberration of voice quality and vocal fatigue, at three months follow-up.ConclusionsThis study shows long-term improvement from behavioral voice therapy, particularly in a group setting. The results indicate the importance of early transfer-to-speech and late posttherapy test to capture whether the goal of voice therapy was fulfilled or not for the patients.     

Voice and Laryngeal Configuration of Men With Unilateral Vocal Fold Paralysis Before and After Medialization

Aim

To describe the laryngeal configuration and the voice of male patients diagnosed with unilateral vocal fold paralysis (UVFP) before and after medialization.

Methods

A retrospective study involving the collection of data from medical records of 142 patients diagnosed with UVFP from January 2003 to April 2009, submitted to auditory-perceptual assessment of voices and visual perception of laryngeal images before and after medialization.

Results

The study included data from 24 male patients, with an average of 60.7 years, who underwent three surgical medialization techniques (injection of hyaluronic acid, type I thyroplasty, and injection of Teflon). Before treatment, the position of the paralyzed vocal fold was seen to have a significant influence to the passing of the healthy vocal fold beyond the midline and on the overall degree of dysphonia. After treatment, the complete glottic closure; the free margin of the linear vocal fold; paralyzed vocal fold in the median position, reduction of hoarseness, roughness and breathiness (more frequently mild), and asthenia (more frequently normal and mild); tension and instability (more frequency normal); and a decrease in the overall degree of dysphonia were found to be significant.

Conclusion

The position of the paralyzed vocal fold influences the position of the healthy vocal fold in relation to the midline and the overall degree of dysphonia. All three treatments improved the glottic configuration and the voice of patients with UVFP.     

Management of Vocal Fold Scar with Autologous Fat Implantation: Perceptual Results

Vocal fold scar disrupts the mucosal wave and interferes with glottic closure. Treatment involves a multidisciplinary approach that includes voice therapy, medical management, and sometimes surgery. We reviewed the records of the first eight patients who underwent autologous fat implantation for vocal fold scar. Information on the etiology of scar, physical findings, and prior interventions were collected. Videotapes of videostroboscopic findings and perceptual voice ratings [Grade, Roughness, Breathiness, Asthenia, Strain (GRBAS)] were randomized and analyzed independently by four blinded observers. Etiology of scar included mass excision (7), vocal fold stripping (3), congenital sulcus (2), and hemorrhage (1). Prior surgical procedures performed included thyroplasty (1), autologous fat injection (9), excision of scar (2), and lysis of adhesions (2). Strobovideolaryngoscopy: Statistically significant improvement was found in glottic closure, mucosal wave, and stiffness (P = 0.05). Perceptual ratings (GRBAS): Statistically significant improvement was found in all five parameters, including overall Grade, Roughness, Breathiness, Asthenia, and Strain (P = 0.05). Patients appear to have improved vocal fold function and quality of voice after autologous fat implantation in the vocal fold. Autologous fat implantation is an important adjunctive procedure in the management of vocal fold scar, and a useful addition to the armamentarium of the experienced phonomicrosurgeon.     

采用氧合血红蛋白吸收带的漫反射光谱比率R（540）/R（575）检测浅表性膀胱癌

采用氧合血红蛋白在540和575 nm吸收带的漫反射光谱比率(R540/R575)对人浅表性膀胱癌进行了鉴别诊断,实验采用带积分球附件的分光光度计获取组织的漫反射光谱。结果表明:正常膀胱的粘膜/粘膜下层组织的漫反射光谱比率(R540/R575)在组织离体后2 h的平均值为111%,3 h的平均值为107%,4 h的平均值为104%,5 h的平均值为102%,而浅表性的膀胱癌的粘膜/粘膜下层组织的漫反射光谱比率(R540/R575)在组织离体后2 h的平均值为98.4%,3 h的平均值为95.5%,4 h的平均值为93.1%,5 h的平均值为91.6%,正常膀胱与浅表性膀胱癌的粘膜/粘膜下层组织在组织离体后2,3,4和5 h的漫反射光谱比率(R540/R575)均有显著性的差异(p<0.05),分别为12.6%,11.5%,10.9%和10.4%。这结论为快速、低成本、非入侵的浅表性膀胱癌的光活检提供了一种新的方法。     

Pretibial cyst formation after anterior cruciate ligament reconstruction using auto hamstring grafts: two case reports in a prospective study of 89 cases

Eighty-nine cases after anterior cruciate ligaments (ACL) reconstruction were followed prospectively with magnetic resonance imaging (MRI). The patients were examined using axial and sagittal MRI at least twice during the postoperative evaluation of reconstructed ACL. Two cases of pretibial cyst formation were observed. At the time of cyst formation, neither patient had any subjective or objective evidence of knee instability. The cyst of one case communicated with the intra-articular. The minimum follow-up period after the surgical excision was 9 months, with no evidence of recurrence. We might speculate that the critical period for cyst formation in both patients occurred at less than 12 months after their ACL reconstruction. We concluded that the cyst formation was most likely due to incomplete graft tendon incorporation within the osseous tunnel.     

The role of intraoperative magnetic resonance imaging in complex meningioma surgery

Intraoperative magnetic resonance imaging (iMRI) has gained importance in the treatment of gliomas and sellar tumors. In intracranial meningiomas, the extent of surgical tumor removal is one of the most important factors in the prevention of tumor recurrence and patient survival. Complex meningiomas located at the skull base or near eloquent brain regions show higher recurrence rates, morbidity and mortality. The aim of this study was to evaluate whether iMRI contributes to more extensive surgical resection in these tumors. Patients undergoing complex meningioma resection using iMRI from January 2007 to January 2011 were included in this study. The indication for iMRI-guided tumor resection included patients presenting with meningiomas located in the skull base or compressing eloquent brain areas in whom a radical resection was considered to be difficult. Intraoperative 0.15-T MRI scan (PoleStar; Medtronic Navigation, Louisville, CO, USA) was performed before and after maximal possible resection using standard microsurgical and neuronavigation techniques. All patients underwent fluorescence-guided resection. The following data were analyzed: tumor localization, histological grade, Simpson resection grade, duration of the procedure, iMRI scan time, iMRI findings, resection extent based on postresection iMRI, hospitalization time, surgical complications and outcome, and MRI follow-up 2–27 months postoperation. Twenty-seven consecutive patients undergoing complex meningioma resection using iMRI were included. In this series, only one patient (3.4%) underwent resection of tumor remnant after iMRI, although without improvement of the Simpson resection grade. Temporary neurologic deficits were found in 8 patients (27.6%) postoperatively, whereas 11 patients (37.9%) had permanent postoperative neurologic deficits. In one case (3.4%), fatal postoperative bleeding occurred which was not detected by iMRI. Our results show that iMRI has no influence on intraoperative strategy in terms of resection grade or detection of early postoperative complications. The benefits of iMRI in complex meningioma surgery are therefore doubtful; however, it may still prove to be effective in certain subsets of complex meningiomas.     

The Voice Performance After Septoplasty With Surgical Efficacy Demonstrated Through Acoustic Rhinometry and Rhinomanometry

ObjectiveTo demonstrate the surgical efficacy of septoplasty using acoustic rhinometry (AR) and anterior rhinomanometry (ARM) and to evaluate the effect of septoplasty on voice performance through subjective voice analysis methods.Materials and MethodsThis prospective study enrolled a total of 62 patients who underwent septoplasty with the diagnosis of deviated nasal septum. Thirteen patients with no postoperative improvement versus preoperative period as shown by AR and/or ARM tests and three patients with postoperative complications and four patients who were lost to follow-up were excluded. As a result, a total of 42 patients were included in the study. Objective tests including AR, ARM, acoustic voice analysis and spectrographic analysis were performed before the surgery and at 1 month and 3 months after the surgery. Subjective measures included the Nasal Obstruction Symptom Evaluation questionnaire to evaluate surgical success and Voice Handicap Index-30 tool for assessment of voice performance postoperatively, both completed by all study patients.ResultsAmong acoustic voice analysis parameters, F0, jitter, Harmonics-to-Noise Ratio values as well as formant frequency (F1-F2-F3-F4) values did not show significant differences postoperatively in comparison to the preoperative period (P > 0.05). Only the shimmer value was statistically significantly reduced at 1 month (P < 0.05) and 3 months postoperatively (P < 0.05) versus baseline. Statistically significant reductions in Voice Handicap Index-30 scores were observed at postoperative 1 month (P < 0.001) and 3 months (P < 0.001) compared to the preoperative period and between postoperative 1 month and 3 months (P < 0.05).ConclusionIn this study, first operative success of septoplasty was demonstrated through objective tests and then objective voice analyses were performed to better evaluate the overall effect of septoplasty on voice performance. Shimmer value was found to be improved in the early and late postoperative periods.     

Effect of a Single Injection of Basic Fibroblast Growth Factor into the Vocal Folds: A 36-Month Clinical Study

ObjectiveA single injection of basic fibroblast growth factor (bFGF) into the vocal folds of patients with glottal insufficiency has been shown to be effective for a few years. However, the long-term therapeutic effect of a single injection of bFGF into the vocal folds has yet to be demonstrated. In this study, the therapeutic effect of a single injection of bFGF into the vocal folds was investigated over several years by monitoring patients for 36 months following this treatment.MethodsNineteen patients with glottal insufficiency received injections of bFGF diluted to 20 μg/mL in the superficial layer of the lamina propria of the bilateral vocal folds. The following parameters were evaluated at preinjection baseline and 6, 12, 18, 24, and 36 months later, and statistical comparisons were performed. The parameters evaluated were: the Grade, Rough, Breathy, Asthenic, and Strained (GRBAS) scale score; maximum phonation time; acoustic analysis; and glottal wave analysis (GWA) and kymograph edge analysis (KEA) using high-speed digital imaging (HSDI). The amplitude perturbation quotient (APQ) and period perturbation quotient (PPQ) were measured by acoustic analysis. The mean minimum glottal area during vocalization and mean minimum distance between the vocal folds were measured by GWA. The amplitudes of the bilateral vocal folds were measured by KEA.ResultsPostinjection, the GRBAS scale score decreased from 6 months after injection, and maximum phonation time was prolonged. The mean minimum glottal area during vocalization and the mean minimum distance between the vocal folds calculated by GWA of HSDI decreased significantly after 6 months. These effects persisted until 36 months postinjection. APQ and PPQ derived from acoustic analysis tended to decrease, but not significantly. There was no clear change in the amplitudes of the bilateral vocal folds calculated by KEA of HSDI before and after injection.ConclusionsThese results suggest that the effects of a single injection of bFGF into the vocal folds persist for 36 months.     

MRI of liver tumors using gadolinium-DOTA: prospective study comparing spin-echo long TR-te sequence and CT

Thirty-nine patients with liver tumors were examined using MRI at 0.5 T before and after intravenous bolus injection of either 0.1 mmol/kg (n = 18) or 0.2 mmol/kg (n = 21) of Gadolinium-Dota, using spin-echo T1-and T2-weighted sequences before injections and spin-echo or gradient-echo sequences after injection. When contrast-to-noise (C/N) data were normalized relative to time, optimal mean C/N was observed after gadolinium injection. However, subjective study and case-by-case C/N measurement showed better contrast for SE 2000/60 and CT with injection in 62% and 42% of cases, respectively.     

Does botulinum toxin alter laryngeal secretionsand mucociliary transport?

Localized botulinum toxin injection disrupts cholinergic transmissionand has potential to cause focal dysautonomia. Mucociliary transport and laryngeal secretions are thought to be mediated in part by autonomic, cholinergic transmission. We questioned whether patients who receive Botox® injection for adductor spasmodic dysphonia (ADSD) report postinjection symptoms possibly related to altered mucociliary clearance or laryngeal secretions. Medical histories, audiotaped interviews, and symptom ratings were retrospectively examined for 29 patients with ADSD who were followed after one or more Botox injections. Patients had received bilateral, percutaneous Botox injections of 2.5 units using an EMG-guided approach. One or more weeks after injection, four patients reported either burning, tickling, or irritation of the larynx/throat, excessive thick secretions, or dryness. Symptoms recurred with subsequent injections in two patients and were not associated with swallowing difficulty. These symptoms are consistent with, but not diagnostic of, the known effects of botulinum toxin on cholinergic, autonomic transmission.     

Comparison of diffusion tensor,dynamic susceptibility contrast MRI and Tc-Tetrofosmin brain SPECT for the detection of recurrent high-grade glioma

Introduction

Treatment induced necrosis is a relatively frequent finding in patients treated for high-grade glioma. Differentiation by imaging modalities between glioma recurrence and treatment induced necrosis is not always straightforward. This is a comparative study of diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI and ^99mTc-Tetrofosmin brain single-photon emission computed tomography (SPECT) for differentiation of recurrent glioma from treatment induced necrosis.

Methods

A prospective study was made of 30 patients treated for high-grade glioma who had suspected recurrent tumor on follow-up MRI. All had been treated by surgical resection of the tumor followed by standard postoperative radiotherapy with chemotherapy. No residual tumor had been found on brain imaging immediately after the initial treatment. All the patients were studied with dynamic susceptibility contrast brain MRI and, within a week, ^99mTc-Tetrofosmin brain SPECT.

Results

Both ^99mTc-Tetrofosmin brain SPECT and dynamic susceptibility contrast MRI could discriminate between tumor recurrence and treatment induced necrosis with 100% sensitivity and 100% specificity. An apparent diffusion coefficient (ADC) ratio cut-off value of 1.27 could differentiate recurrence from treatment induced necrosis with 65% sensitivity and 100% specificity and a fractional anisotropy (FA) ratio cut-off value of 0.47 could differentiate recurrence from treatment induced necrosis with 57% sensitivity and 100% specificity. A significant correlation was demonstrated between ^99mTc-Tetrofosmin uptake ratio and rCBV (P = 0.003).

Conclusions

Dynamic susceptibility contrast MRI and brain SPECT with ^99mTc-Tetrofosmin had the same accuracy and may be used to detect recurrent tumor following treatment for glioma. DTI also showed promise for the detection of recurrent tumor, but was inferior to both dynamic susceptibility contrast MRI and brain SPECT.     

Long-term preservation of voice improvement following surgical medialization and reinnervation for unilateral vocal fold paralysis

In June of 1996, we reported improved functional voice results when reinnervation was combined with surgical medialization for unilateral vocal fold paralysis. In addition, it was noted that further wasting of the reinnervated vocal fold was prevented in 96% of these patients beyond 2 years' follow-up. The study reported here compares the long-term preservation of voice improvement achieved by surgical medialization alone with that resulting from combined medialization and nerve-muscle pedicle reinnervation. Further significant wasting of the paralyzed vocal fold with voice deterioration from that achieved by surgical medialization alone was noted between 6 months and 2 years postoperatively in 28% of patients, while only 4% of those undergoing combined reinnervation demonstrated this finding at a minimum of 2 years' follow-up.