The vocal fold mucosa has vibratory properties that are supported by specific histological structures, including the layer structure and wide distribution of hyaluronic acid. When the mucosa is scarred, the vibratory property is deteriorated, which leads to severe permanent dysphonia. No optimal treatment has yet been established. Hepatocyte growth factor (HGF) has a strong anti-fibrotic function and has been proven to resolve fibrosis and regenerate the original tissues in lung and kidney in animal experiments. We have additionally shown that HGF can resolve fibrotic tissues in vocal fold scars and improve the vocal function in animal models. Based on these pre-clinical data, a phase I/II exploratory clinical trial was planned for the assessment of the regeneration of the vocal fold in patients with vocal fold scar and sulcus. A GMP-compatible recombinant human HGF protein drug (KP-100LI; Kringle Pharma, Inc., Osaka) was injected into the scarred vocal folds under topical anesthesia. Three different dosages (1, 3, and 10 µg) for 1 side of the vocal fold were used for each group of patients. The injection was repeated weekly, up to four times. The patients were followed for six months after the treatment. The results indicated significant improvement of the vocal fold vibratory amplitude, voice handicap index (VHI)-10, and GRBAS scale. No severe adverse events were noted. These findings suggest that HGF is effective for promoting regeneration of the vocal fold in patients with vocal fold scar and sulcus.

The present study evaluated the clinical application of functional electrical stimulation (FES) to restore the laryngeal function in patients with vocal fold paralysis.

Canines were used in this study. We designed an electrode array consisted of 8 active platinum disk electrodes, mounted on a 10 × 8 × 1 mm silicone plate. This electrode array was placed between the thyroid cartilage and thyroarytenoid muscle. The vocal fold angle from the anterior commissure to the vocal process was measured endoscopically in the anesthetized animal. To clarify the influence of FES on reinnervation, the animals were divided into reinnervated and denervated groups. In the reinnervated group, the right recurrent laryngeal nerve was sectioned and repaired immediately. In the denervated group, the right recurrent laryngeal nerve was sectioned and not repaired.

In the reinnervated group, FES induced optimal glottal closure with a low current. The vocal fold easily adducted to the midline. Even in the denervated group, FES was able to induce vocal fold adduction. However, the induced adduction was very small, and a high current was required to move the vocal fold. The vocal fold gradually moved from the medial to the lateral side over 3 minutes of continuous stimulation, but adduction of the paralyzed vocal fold have sustained and positioned over the midline for 2 minutes.

This study showed that paralyzed adductor muscle stimulation with new shaped electrodes was able to induce optimal glottal closure. Vocal fold adduction by FES was assumed to be sufficient to improve the voice sounds in cases of unilateral vocal fold paralysis.

We investigated the treatment outcomes of 52 patients with locally advanced laryngeal squamous cell carcinoma (L-SCC) who were treated with selective radiotherapy and concomitant intra-arterial cisplatin (RADPLAT) at Kurume University Hospital between January 2006 and September 2016. Twenty-seven of the 52 patients had supraglottic cancer, 21 had glottic cancer, and 4 had subglottic cancer. The disease stages of the patients were as follows: Stage Ⅱ, n=8; Stage Ⅲ, n=33; and Stage Ⅳ-A, n=11. The 5-year locoregional control, disease-specific survival, and overall survival rates of all patients were 88%, 87%, and 82%, respectively. The 5-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates were 90%, 78%, and 76%, respectively. The incidence rates of grade >3 hematologic toxicities were as follows: leukopenia, 12% (n=6); neutropenia, 14% (n=7); and anemia, 4% (n=2). The incidence rates of non-hematologic toxicities were as follows: for mucositis, 4% (n=2); and dysphagia, 2% (n=1). RADPLAT was considered safe and feasible for patients with L-SCC and may have the advantage of achieving long-term larynx preservation.

Treatment of laryngeal cancer mainly consists of radiation therapy, chemoradiotherapy and surgery. For organ preservation surgery, transoral surgery or open partial laryngectomy are the treatments of choice. Of these, transoral surgery is the least invasive, allowing for a direct approach to the lesions. In our institution, we practice two modalities for transoral surgery. Transoral laser microsurgery (TLM) is indicated for glottic cancer, which has a narrow working space. In contrast, transoral videolaryngoscopic surgery (TOVS) is indicated for supraglottic cancer, since the working space is relatively wide and the lesion can be visualized from various directions using a laryngeal endoscope. In glottic initial cases (Tis, T1-2 and 1 case of T3), the 5-year overall survival (OS), disease-specific survival (DSS), larynx preservation rate (LPR), local control rate (LCR) and laryngoesophageal dysfunction-free survival (LEDFS) were 90.3%, 95.7%, 95.1%, 78.5% and 75.2%, respectively. Good oncological results can be expected in Tis, T1-T2 glottic cancer; however, T1b cases are not a good indication for TLM because of the high incidence of glottic web formation. In radiorecurrent salvage TLM for rT1-rT2 lesion, the 5-year OS, DSS, LPR, LCR and LEDFS were 86.2%, 91.3%, 83.9%, 71.8% and 67.3%, respectively. Acceptable oncological results were obtained for rT1-rT2 lesions. A relatively large surgical margin is recommended in radiorecurrent cancer. In supraglottic cancer with T1-T3 lesions, the 5-year OS, DSS, LPR, LCR and LEDFS were 73.0%, 88.2%, 89.4%, 88.1% and 67.3%, respectively. A good organ preservation rate was achieved, and the swallowing function was preserved except for in one case. Considering the laryngeal cancer treatment guidelines, T1-T2 and rT1-rT2 lesions can be indicated for transoral surgery, and in experienced institutions, select T3 lesion can also be indicated for transoral surgery.

Open partial laryngectomy is a type of salvage surgery for radiation failure in early-stage laryngeal carcinoma. We herein report the results of early-stage laryngeal carcinoma cases treated in our institute. Of 356 cases, 91% were treated by radiation, and residual or recurrent disease at primary site was observed in 43 cases (13%). Larynx-preserving salvage surgery was performed in 26 (60%) cases. The 5-year overall survival (OS) rate was 96% in T1N0 glottic, 89% in T2N0 glottic, 64% in T1N0 supraglottic, and 60% in T2N0 supraglottic carcinoma. Salvage fronto-lateral partial laryngectomy was performed in 18 cases, and the 5-year OS after salvage surgery was 88% without any primary site recurrence, with all patients able to manage with oral intake only and no need for tracheostoma.

The simultaneous pursuit of functional preservation and a disease cure in supracricoid laryngectomy (SCL) for laryngeal cancer requires adequate case selection and resection with careful consideration of surgical indications and limitations. This article describes the resection line of SCL with specific examples and assesses the validity of this line in order to review the indications and limitations with regard to the resection line.

The normal and critical resection lines are both defined at five sites in order of resection: anterior, superior, lateral, posterior, and inferior side of the larynx.

In the present study, treatment outcomes were assessed in 30 patients with laryngeal cancer who underwent SCL, including 2 cases of supratracheal laryngectomy, in our hospital from March 2013 to February 2019. The 5-year overall survival, disease-free survival, and laryngeal function preservation rates were 92.3%, 85.2%, and 89.9%, respectively. These results supported the validity of the resection line we employed.

Precisely understanding the resection line permits an adequate and flexible response to patients pre-and -intraoperatively and facilitates meeting the seemingly conflicting goals of functional preservation and a disease cure. Eventually, the number of patients to avoid total laryngectomy is expected to increase.

Fat injection laryngoplasty (FIL) is a widely accepted form of augmentation surgery. We herein report the features of autologous fat as an injection material and describe the indications and technical tips concerning FIL. We also conducted a clinical analysis of FIL cases in our institute and describe the findings. The advantages of autologous fat include not only the lack of any immune reaction after its injection but also its viscosity, which closely resembles that of the superficial layer of the lamina propria of the vocal fold. The most suitable indication of FIL is for unilateral vocal fold paralysis in order to medialize the fixed vocal fold. Atrophy and scarring of the vocal fold as well as sulcus vocalis can also be a target pathological condition, as those disease cause loss of volume of the membranous portion of the vocal fold. An analysis of the FIL cases in our institute since 2008 to 2017 showed that consecutive data of MPT, MFR, PPQ and APQ, which are objective voice findings, improved at 1, 3, 6 and 12 months after surgery compared to preoperative voice examination findings. Subjective findings, such as the VHI-10 and V-RQOL, also improved. Both objective and subjective values are stable at three months after FIL. Based on the present and previous findings, FIL seems to be effective in the mid- to long-term period.

Injection laryngoplasty is part of an effective procedure for treating unilateral vocal fold paralysis. Many different materials are available for injection, and we have been using calcium phosphate cement (BIOPEX^®). The procedure for preparing and injecting BIOPEX^® is quite simple, and it is highly biocompatible material. BIOPEX^® is injected into the paraglottic space under general anesthesia with under laryngeal exposure. It hardens immediately and changes to solid calcium after injection, pushing the glottis to the internal side. The injection of BIOPEX^® results in the same treatment outcome as laryngoplasty type I. In the present study, we investigated the postoperative voice outcome and complications after injection of BIOPEX^® in 47 patients with unilateral vocal fold paralysis. There were no postoperative infections due to BIOPEX^® or severe laryngeal edema that required tracheostomy. The postoperative maximum phonation time (MPT) improved significantly to 12.1 seconds from 4.0 seconds before surgery, and the postoperative mean flow rate (MFR) improved significantly to 257ml/min from 580 ml/min before surgery. At 2 years after the surgery, 87.8% BIOPEX^® still remained in the paraglottic space, and no side effects were caused over this long term. These results indicate that BIOPEX^® is extremely safe with a favorable treatment outcome for injection to the human larynx.

Injection laryngoplasy is a typical treatment for glottal insufficiency. In Japan, silicone, collagen, autologous fat, calcium phosphate cement, and fibroblast growth factor have been used as injectable materials.　However, none of these materials meets all of the ideal conditions, such as good biocompatibility, no absorbability, no migration, and ready formulation for easy injection.

Hyaluronic acid (HA) is a component of the extracellular matrix that plays a key role in tissue viscosity, shock absorption, wound healing, and space filling. Research into the role of HA in laryngology indicates that it has profound effects on the structure and viscoelastisity of vocal folds.

Injection laryngoplasty using HA of two different types of hardness was performed on 20 patients with glottal insufficiency. The results were compared preoperatively and at 1, 3, 6, 12, and 24 months postoperatively by acoustic and aerodynamic analyses and self-assessment (Voice Handicap Index-10 [VHI-10]).

For augmentation of vibrating part of vocal fold, injection laryngoplasty with soft type of HA was significantly effective for 12 months by Maximum Phonation Time (MPT), Pitch Perturbation Quotient (PPQ), and VHI-10.

For medialization of vocal fold, injection laryngoplasty using hard type of HA was significantly effective for 24 months by MPT.

Preoperative examination : We created multi-planar reconstruction images from neck computed-tomography (CT) images. The form of the thyroid cartilage, position of the vocal folds, and degree of vocal fold atrophy can be evaluated from these images.

Type I thyroplasty : The fenestration design is a first-line priority during surgery. Although a chondrotomy is accomplished using a scalpel, a fissure bur may be necessary in cases with cartilage ossification. The fenestration is carefully created with the aim of preserving the cartilage and inner perichondrium. The vocal fold medialization procedure considers and adjusts to postoperative atrophy.

Titanium implant for type I thyroplasty : We examined the stability and permanence of fixation afforded by the titanium medialization laryngoplasty implant (TMLI), which was developed by the lead author. We evaluated implant migration, deformation, and fracture based on the postoperative neck CT images of 73 patients; however, no patients experienced any of these conditions. Thus, our results confirmed the stability and permanence of fixation following the placement of the TMLI. The implant also performed adequately in cases of reoperation.

Adductor spasmodic dysphonia (AdSD) is a rare voice disorder characterized by a strained and strangled voice quality with intermittent phonatory breaks and adductory vocal fold spasms. TypeⅡthyroplasty attempts to achieve the slight lateralization of the vocal folds by expanding the thyroid cartilage anteriorly. The success of the surgery depends entirely on whether or not the incised thyroid cartilage can be laterally expanded to an adequate width under voice monitoring and then fixed permanently with titanium bridges. The titanium bridge is an investigational device employed during the practice of typeⅡthyroplasty, used to widen the anterior area of the connected vocal fold at determined intervals in order to relieve symptoms of AdSD. The device is biocompatible and made from medical-grade titanium material. This paper will focus mainly on relevant surgical tips and the long-term outcomes of the procedure.

Improvement of breathy dysphonia due to unilateral vocal fold paralysis (UVFP) is usually achieved by implementing various kinds of phonosurgical procedures, including intracordal injection, type I thyroplasty, arytenoid adduction (AA), and combinations thereof. However, some patients do not recover their “normal” voices after surgery. Normal voices can be attained by providing the immobile vocal fold with the median location and symmetrical bulk and tension of the unaffected vocal fold. Because phonosurgical procedures offer “static” adjustment of these features, the thyroarytenoid muscle (TA) does not work as the body of the immobile vocal fold, resulting in little contribution to voice production and tuning. The authors refined the technique of nerve-muscle pedicle (NMP) flap implantation onto the TA muscle and have applied this innovative method, together with AA, in the treatment of breathy dysphonia due to UVFP since July 2002. Ninety-six patients had undergone NMP flap transfer and AA as of July 2016. The operative procedures are described in detail. Long-term follow-up over 2 years in 47 patients revealed significant improvement in the phonatory function after surgery. Furthermore, most parameters showed significant improvement during the follow-up period.

Understanding the three-dimensional (3D) movement of immobile vocal folds (VFs) is very important. Because endoscopic findings reflect only the two-dimensional movement of VFs, it is impossible to obtain a correct diagnosis. The cases presented in this article include not only those of unilateral vocal fold paralysis (UVFP) but also arytenoid dislocation, laryngeal scarring and other statuses. The main diseases are described below.

UVFP : Even in cases of light UVFP, the paralyzed arytenoid is passively displaced cranially during phonation. Some surgical procedures may be applied to manage UVFP, but only arytenoid adduction can resolve this passive movement. I will also describe several specific types of UVFP, such as adductor branch paralysis (AdBP).

Arytenoid dislocation (AD) : AD can be divided into two types: posterior and anterior dislocation. Our 3D computed tomography (CT) study revealed that posterior AD is very rare and often misdiagnosed as AdBP (and vice versa). We detected two subtypes of anterior AD: cranial and caudal. The VFs in cases of caudal AD are located in the mid position, and the patient’s voice is not severely affected; as such, these cases are sometimes misdiagnosed as medial UVFP.

Other types of immobile VF : A number of rare and unique types of immobile VF have been reported, such as scarring after intubation or trauma, fracture, congenital and VF of many other causes. Endoscopy is insufficient for understanding what happens to a patient’s immobile VF However, 3DCT can reveal the actual status of these cases.

With the exception of a few cases that become cancerous, laryngeal papilloma is fundamentally a benign disease. At the same time, however, it is also a refractory disease that causes very serious impairments in respiratory and phonatory functions. Human papillomavirus (HPV), a cause of these papillomas, infects not only the site of the tumor, but also the surrounding laryngeal mucosa. Thus, recurrent laryngeal papillomatosis (RLP) is both a neoplastic disease and an infectious disease.

HPV-DNA tests for various laryngeal diseases were performed to investigate whether there was HPV infection of the larynx. All patients with non-neoplastic diseases were negative for HPV. In vocal cord leukoplakia and laryngeal cancer, HPV-31 was detected in 2 of 68 patients, but all others were negative. With papilloma, on the other hand, HPV-6/11 was detected at a high rate.

Treatment for laryngeal papilloma requires surgery for the tumor and treatment for the infection. Efforts are made to use low invasive surgery that does not leave postoperative scarring. Adjuvant therapy for RLP includes cidofovir, HPV vaccination, herbal medicine, and bevacizumab. In our hospital, combination therapy with HPV quadrivalent vaccine and surgery began in 2012, and it has been able to inhibit recurrences in 70% of cases of RLP. With this treatment method, anti-HPV antibodies are induced in the laryngeal mucus with vaccination, inhibiting re-infection with HPV. RLP treatments that aim for a complete cure with elimination of HPV from the larynx and resection of the tumor should be considered.

Objectives: Severe subglottic stenosis (SGS) remains a challenge to manage. This case series study investigated the clinical course and treatment outcome of pediatric SGS at our institution .

Method: The medical charts of children were reviewed. Data included demographics, causes of disease, management, and treatment outcome.

Results: Nine patients were diagnosed with SGS and eight of them were treated between October 2010 and September 2017 at our institution. In all patients, SGS had been acquired and graded as 3 or 4, according to the Cotton-Myer classification. SGS had been caused by intubation in 7 cases, and the duration of intubation ranged from 7 to 86 days (median: 25.5 days). In the remaining two cases, the causes of SGS were surgery and penetrating trauma. Seven patients were treated with the “Trough method”, while one was treated with micro-laryngeal surgery. Decannulation was achieved in four cases, but a small tracheostomy fistula remained in other two cases in which the SGS was improved. In another patient, treatment was withheld due to compilation of the trachea defect following penetrating trauma, and in the other, treatment was rejected after re-stenosis occurred following management with the Trough method. The causes of re-stenosis and the need for multiple surgeries included granulation and scar formation around the superior tip of the T-tube that had been inserted into the trough.

Conclusion: The Trough method is a safe and technically simple procedure, and it could be a therapeutic option for SGS.

Background: Endoscopic Laryngo-Pharyngeal Surgery (ELPS) has been performed for supraglottic cancer to preserve the laryngeal function. The aim of this study was to verify the feasibility and usefulness of partial laryngectomy using ELPS for supraglottic cancer.

Materials and Methods: Between 2008 and 2018, 62 patients with supraglottic cancer underwent ELPS. The outcomes, including the laryngeal function and survival rates, are reviewed.

Results: Tracheostomies were required to create the surgical field in 10 patients. Fortunately, all tracheostomas were able to be closed. Overnight intubation was required to avoid dyspnea due to laryngeal swelling in nine patients. All patients who underwent ELPS retained their voice function and were able to consume food orally without the need for tube feeding at the time of discharge. The overall 3 and 5-year survival rates were 88.1% and 84.5%, respectively. No patients have died of their disease thus far. The 5-year cause-specific survival rate was 100%.

Conclusions: Partial laryngectomy using ELPS for supraglottic cancer is feasible and useful in terms of the oncological outcome and preservation of the laryngeal function.

To investigate the prognostic significance of the pretreatment inflammatory biomarkers in patients with local advanced laryngeal and hypopharyngeal cancer who received total laryngectomy or laryngopharyngectomy, 32 laryngeal cancer patients and 44 hypopharyngeal cancer patients were enrolled, and the impact of pretreatment inflammatory biomarkers, including fibrinogen, Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and C-reactive protein-to-albumin ratio (CAR) on the survival of these patients were evaluated. These markers were categorized into two groups according to the results of receiver-operating characteristic plots for the determination of the respective cut-off values. In the present study, CAR Ⅳ0.049 was associated with a poor overall survival (OS) and progression-free survival (PFS) in patients with local advanced laryngeal and hypopharyngeal cancer. Our multivariate analysis revealed that CAR Ⅳ0.049 was an independent prognostic factor for the OS and PFS. These results suggested that CAR was a useful pretreatment predictive biomarker for the survival of local advanced laryngeal and hypopharyngeal cancer patients who received total laryngectomy or laryngopharyngectomy.

We conducted a retrospective review of the medical records of vocal fold paralysis (VFP) patients between January 2016 and April 2018 at the ENT outpatient clinic of Tohoku University Hospital and evaluated the patient characteristics, the causes of VFP, and the prognosis. A total of 168 VFP patients (104 men, 64 women) were enrolled in this study. One hundred and seven (63.7%) left, 37 (22.0%) right, and 24 (14.3%) bilateral vocal folds were impaired. The main causes of VFP were neoplastic disease (65 patients), cardiovascular disease (44 patients), idiopathic (21 patients), and intubation (16 patients). Thirty-two patients exhibited recovery from the VFP during the follow-up period, and 30 of those (93.8%) had recovered within 6 months from the onset. The recovery rate varied considerably for each cause of the VFP. We performed 37 framework surgeries to improve the voice quality of unilateral VFP patients. In the future, a greater number of early interventions for unilateral VFP, such as injection laryngoplasty or voice treatment, will be needed at the ENT outpatient clinic.

Several cardiopulmonary diseases are associated with left recurrent laryngeal nerve palsy. The syndrome is termed cardiovocal syndrome or Ortner syndrome. The compression of the left recurrent nerve between the aorta and pulmonary artery is suggested to be responsible for the palsy.

We herein report a case of juvenile cardiovocal syndrome due to mitral valve regurgitation. The patient was a 16-year-old boy who had been found to have mitral valve regurgitation at 9 years old and been observed without operation. - He presented with hoarseness at 15 years of age, and left recurrent laryngeal nerve palsy had been noted.- The cause of the paralysis was suspected to be compression by the extended pulmonary artery following mitral valve regurgitation. The patient was observed during his second growth period and successfully treated with type I thyroplasty and arytenoid adduction at 19 years old after the maturation of the laryngeal framework had been confirmed.

We must remember that cardiopulmonary diseases can cause left recurrent laryngeal nerve palsy and the timing of surgery for pediatric patients must be decided carefully.

For severe dysphagia, surgical treatments are considered if conservative approaches are not effective. Central-part laryngectomy (CPL) is a surgical approach for treating intractable aspiration. In this procedure, the area of the glottis including the mid-part of the thyroid cartilage and cricoid cartilage is removed in order to separate the digestive tract from the airway. It is less invasive than ordinary total laryngectomy because the lateral part of the thyroid cartilage, the whole hypopharyngeal mucosa, superior laryngeal artery and nerve, and the epiglottis are conserved. Furthermore, a simple pharyngeal tract is formed by cutting the cricopharyngeal muscle, which facilitates oral intake after surgery. We performed CPL for 2 cases (a 44-year-old man with Wallenberg syndrome and a 75-year-old man after tongue cancer surgery) to prevent severe aspiration. After surgery, both patients achieved oral food intake, and alternative nutrition became unnecessary. This procedure is extremely useful not only for preventing aspiration but also for achieving oral intake after surgery.

Percutaneous dilatational tracheostomy (PDT) is considered a relatively safe and simple procedure and is widely performed worldwide. However, PDT carries a risk of mispuncture in cases with anatomic mutations and postoperative complications, such as structural disruption and tracheal stenosis. A 78-year-old male was admitted to the previous hospital due to exacerbating heart failure. For intensive respiratory care, endotracheal intubation and subsequent PDT were performed. Thereafter, tracheal stenosis occurred. He was admitted to our department for a further evaluation and treatment. On an examination, the trachea was completely obstructed below the first tracheal ring. Computed tomography showed complete obstruction of the trachea with destruction of the tracheal anterior wall. Furthermore, remarkable thoracic spine deformity and tracheal deviation were noted. To remove the obstruction and better manage the airway, an operation was performed via the transoral and transcervical approaches, and a polyglycolic acid sheet and gauze with tetracycline hydrochloride ointment were placed to maintain the intratracheal lumen and prevent tracheal re-stenosis. The anatomical structures of chest and neck should be carefully evaluated before the type of tracheostomy is decided, and PDT should be avoided when there is an evident cervical or thoracic anatomical abnormality.